PMID- 7980481 TI - Model phylogenies to explain the real world. AB - Phylogenetic trees based on gene sequence data contain information about the evolutionary processes responsible for their genesis. Methods have now been developed which help to reveal those processes. The methods are based on simple models of evolutionary change but, when applied across individuals in a population, rather than across species in a higher-level taxon, they can reveal the past history of population change. Examples from salamanders and viruses are used to illustrate how the past history of changes in speciation rate and the origin of epidemics can be inferred in the absence of fossil material or historical documentation. PMID- 7980480 TI - Endo-exonucleases: enzymes involved in DNA repair and cell death? AB - Endo-exonucleases from E. coli to man, although very different proteins, are multifunctional enzymes with similar enzymatic activities. They probably have two common but opposing biological roles. On the one hand, they promote survival of the organism by acting in recombination and recombinational DNA repair to diversify and help preserve the genome intact. On the other hand, they degrade the genomic DNA when it is damaged beyond repair. This ensures elimination of heavily mutagenized cells from the population. PMID- 7980482 TI - Specificity in splicing. AB - Considerable information about the process of pre-mRNA splicing has accumulated, but the mechanism by which highly accurate splicing is achieved is unresolved. Fifteen years ago we proposed that accuracy in splicing might depend on small RNA molecules (splicer RNAs) which hybridise across adjacent exon termini, or intron termini. Gene expression, including alternative splicing, could be controlled by the transcription of specific splicer RNA genes. We re-assess our model here, in the light of subsequent developments. PMID- 7980483 TI - Arabidopsis thaliana, a plant Drosophila. AB - Arabidopsis thaliana is a small cruciferous weed which grows naturally, mainly in Europe. Because of its qualities of small size, rapid growth, low chromosome number and self-fertilisation, I adapted it to aseptic growth in purified agar in sterile test-tubes. I found that it secreted various substances into the medium, but not in type or amount likely to interfere with the expression of biosynthetic mutants. Following X-irradiation of seed, I obtained a number of mutants, including several lethals. One lethal mutant I discovered to be deficient in thiamine synthesis. It was the first biosynthetic mutant to be found in flowering plants. PMID- 7980484 TI - Molecular biology of embryonic development: how far have we come in the last ten years? AB - The successes of molecular developmental biology over the last ten years have been particularly impressive in those directions favored by its major paradigms. New technologies have both guided and been guided by the progress of the field. I review briefly some of the major insights into embryonic development that have derived from research in four specific areas: early embryogenesis of various forms; 'pattern formation'; evolutionary conservation of regulatory elements; and spatial mechanisms of gene regulation. There remain many major problem areas, some of which may require new orientations to solve. PMID- 7980486 TI - Plant developmental biology: green genes for the 21st century. PMID- 7980485 TI - Vertebrate embryonic inductions. PMID- 7980487 TI - Biological pattern formation: new observations provide support for theoretical predictions. PMID- 7980488 TI - Gene targeting in the mouse. AB - Mice with alterations to specific endogenous genes can be produced by gene targeting in embryonic stem cells. The field has developed rapidly over the past decade, so that large numbers of mice with different gene deficiencies have been generated. Knockout mice provide an ideal opportunity to analyse the function of individual mammalian genes and to model a range of human inherited disorders. This powerful approach has also identified numerous examples of gene redundancy and has highlighted the need to consider metabolic differences between man and mouse in disease modelling. More sophisticated gene-targeting methods are now being used to introduce subtle gene alterations. In the future, more refined genetic analysis and genome, rather than individual gene, alterations will be achieved by incorporating site-specific recombination into targeting strategies. Gene targeting could also make a contribution to improved protocols for gene therapy. PMID- 7980489 TI - Mitosis. AB - Within the last decade, the study of mitosis has evolved into a multidisciplinary science in which findings from fields as diverse as chromosome biology and cytoskeletal architecture have converged to present a more cohesive understanding of the complex events that occur when cells divide. The largest strides have been made in the identification and characterization of regulatory enzymes (kinases and phosphatases) that modulate mitotic activity, as well as a number of the proteins and structural components (spindle, chromosomes, nuclear envelope) which carry out the mitotic instructions. One emerging theme appears to be that molecular signalling, which can involve modification of components (such as phosphorylation) or even their specific destruction, monitors the state of the mitotic cell at all stages. One of the major challenges for the future will be the identification of additional targets of the signalling machinery, as well as new regulatory components and their targets on the chromosomes, on the spindle, and at the cleavage furrow. PMID- 7980490 TI - DNA repair: looking back and peering forward. PMID- 7980491 TI - Transcription by RNA polymerase II: a process linked to DNA repair. AB - The proteins that are implicated in the basal transcription of protein coding genes have now been identified. Although little is known about their function, recent data demonstrate the ability of these proteins, previously called class II transcription factors, to participate in other reactions: TBP, the TATA-box binding factor, is involved in class I and III transcription, while TFIIH has been shown to possess components that are involved in the DNA repair mechanism. The involvement of some if not all of the TFIIH subunits in transcription and repair may explain the heterogeneity of the various and sometimes completely unrelated symptoms observed in xeroderma pigmentosum, Cockayne Syndrome and trichothiodystrophy disorders. PMID- 7980492 TI - Chromatin structure and dynamics. PMID- 7980493 TI - The impact of molecular biology on models for cell adhesion. PMID- 7980494 TI - Advances in immunology. AB - Much was accomplished in the last decade in understanding how the adaptive immune system evolved to combat pathogens. Essential features of antigen presentation and T lymphocyte recognition were deciphered, setting the stage for further studies that elucidated basic elements of lymphocyte differentiation (including positive and negative selection during lymphocyte ontogeny) and the major interactions that occur among cells in secondary lymphoid organs in an ongoing immune response. The major challenges of today are found in the burgeoning fields of programmed cells death, enzymology of recombination and somatic mutation, development of memory, and the recognition of pathogens by unconventional lymphocytes. PMID- 7980495 TI - Recent advances in drug design methods: where will they lead? AB - Drug design methods have made significant new advances over the last ten years, mainly in the areas of molecular modelling. In more recent times important developments in theory have led to a different type of modelling becoming possible, the so-called de novo or automated design algorithms. In this new method the programs perform much of the chemist's thinking, in finding appropriately sized chemical groups to fit into a target site. However this is a combinatoric problem which has no general analytical solution; it is ripe for optimization. Other advances, such as combinatorial chemical synthesis and screening, will dramatically influence the search for new lead structures for target sites, which at present are poorly understood. Already these methods are being applied to peptide libraries. Peptides do not make good drug compounds because of their poor bioavailability; further, their flexibility reduces their affinity. In some cases peptide backbones can be removed and replaced with rigid non-peptide scaffolds. PMID- 7980496 TI - Molecular chaperones in cellular protein folding. AB - The discovery of 'molecular chaperones' has dramatically changed our concept of cellular protein folding. Rather than folding spontaneously, most newly synthesized polypeptide chains seem to acquire their native conformation in a reaction mediated by these versatile helper proteins. Understanding the structure and function of molecular chaperones is likely to yield useful applications for medicine and biotechnology in the future. PMID- 7980497 TI - Functional mapping of the human genome by cDNA localization versus sequencing. PMID- 7980498 TI - Molecular evolution: codes, clocks, genes and genomes. AB - The discoveries, advancements and continuing controversies in the field of molecular evolution are reviewed. Topics summarized are (1) the evolution of the genetic code, (2) gene evolution including the demonstration of homology, estimation of sequence divergence, phylogenetic trees, the molecular clock and the origin of genes and gene families by various genetic mechanisms, and (3) eukaryotic genome evolution, including the highly repeated satellite sequences, the interspersed and potentially mobile repeated sequences and the unique sequence fraction of the genome. PMID- 7980499 TI - Accurate determination and physicochemical properties of rat liver nuclear retinoic acid (RA) receptors. AB - The present study was undertaken to establish a novel in vitro method for quantitative determination of the nuclear RA receptors in rat liver. Binding characteristics of RA receptors (free of any contaminating cytoplasmic proteins), in relation to various physicochemical conditions, were evaluated. Three different binding sites for all-trans RA were found in nuclear proteins of rat liver. One of them represents a high affinity and low capacity RA specific binding site with Ka1 0.687 +/- 0.294 x 10(9) M-1 and the Bmax1 0.644 +/- 0.397 pmol/mg protein. Others represent low affinity and high capacity RA non-specific binding sites with Ka2 2.694 x 10(6) M-1; Bmax2 225 pmol/mg protein and Ka3 0.131 x 10(6) M-1; Bmax3 1125 pmol/mg protein, respectively. PMID- 7980500 TI - Role of phosphatidylinositol-3-kinase in insulin receptor signaling: studies with inhibitor, LY294002. AB - In order to study the role of phosphatidylinositol-3-kinase (PI3K) in insulin action, we employed a specific inhibitor of PI3K, LY294002, and measured five biological functions of insulin in mouse 3T3 fibroblasts overexpressing human insulin receptors. LY294002 had no effect on tyrosine phosphorylation of both the insulin receptor beta-subunit and insulin receptor substrate 1 (IRS-1) and did not influence the association of the p85 subunit of PI3K with IRS-1. However, LY294002 partially inhibited insulin stimulated glucose uptake, amino acid uptake and protein synthesis, while it completely inhibited insulin stimulation of DNA synthesis and p70 S6 kinase activation. These data suggest that: 1) PI3K plays a crucial role in various functions of insulin; and 2) there exist multiple signaling pathways (both PI3K dependent and PI3K independent) for the insulin receptor. PMID- 7980501 TI - Differential expression of protein kinase C isoform genes in three murine erythroleukemia cell variants: implication for chemical induced differentiation. AB - The presence of alpha, delta, epsilon, theta, and zeta protein kinase C isoforms in DS19 murine erythroleukemia cells has been established in this study. In addition, the mRNA levels of these isozymes have been measured by quantitative reverse transcriptase-polymerase chain reaction. Isoform delta has been found to be the most abundant isotype, whereas isoform zeta resulted to be present in only few copies. Furthermore, the expression levels of all five protein kinase C isozymes have been studied in three cell clones, derived from parental DS19 cells and characterized by different susceptibilities to differentiation. This comparative analysis indicated that the calcium-independent isozymes (delta, epsilon, zeta, and theta) display significantly higher expression levels in cells less prone to differentiation. On the other hand, the mRNA levels of the only calcium-dependent isoform present (alpha) fluctuate poorly from one cell clone to the other, but are the highest in the cell clone characterized by the fastest rate of differentiation. This study represents the first complete characterization of the basal levels of specific protein kinase C isotypes in different murine erythroleukemia cell clones and provides further evidence for the role of individual isozymes in the early events that trigger chemical induced murine erithroleukemia cell differentiation. PMID- 7980502 TI - Role of Fas ligand in apoptosis induced by hepatitis C virus infection. AB - To investigate the role that Fas ligand plays in the apoptosis of hepatocytes induced by hepatitis C virus infection, we isolated a cDNA clone for human Fas ligand and examined the expression of Fas ligand in liver-infiltrating mononuclear cells obtained from patients with chronic hepatitis C. The amino acid sequence of human Fas ligand showed 76% and 77% identity with those of rat and mouse Fas ligand, respectively. When the expression of Fas ligand transcripts was tested by reverse transcription-polymerase chain reaction, the amplified signal was detected in liver-infiltrating mononuclear cells and peripheral blood mononuclear cells, whereas only a weak signal or none at all was detected in liver tissues. These findings suggest that the Fas ligand-Fas antigen system may play an important role in liver cell injury by hepatitis C virus infection. PMID- 7980503 TI - Rapid effects of aldosterone on free intracellular calcium in vascular smooth muscle and endothelial cells: subcellular localization of calcium elevations by single cell imaging. AB - Rapid in vitro effects of aldosterone on the intracellular concentrations of sodium, potassium and calcium, cell volume and the sodium-proton-antiport have been described in human mononuclear leukocytes and vascular smooth muscle cells (VSMC). These nongenomic effects are signalled through membrane receptors with a high affinity for aldosterone, but not for cortisol, and through the phosphoinositide pathway. In the present study, we demonstrate that free intracellular calcium is increased rapidly by aldosterone in VSMC and endothelial cells (EC) as determined by single cell imaging of Fura2-fluorescence. In VSMC, calcium elevation is localized to the perinuclear region whereas in EC, a predominant increase of subplasmalemmal calcium is seen. In VSMC, effects are half maximal at 0.1 nM aldosterone; cortisol is inactive up to 0.1 microM. These data show that intracellular signalling for aldosterone also involves calcium, but the subcellular localization of this signal varies between cell types. PMID- 7980504 TI - Chronic progressive external ophthalmoplegia is associated with a novel mutation in the mitochondrial tRNA(Asn) gene. AB - Chronic progressive external ophthalmoplegia (CPEO) is caused by a decreased oxidative phosphorylation (OXPHOS) activity due to large-scale deletions of the mitochondrial genome in 50% of the patients. The deletions encompass structural OXPHOS genes as well as tRNA genes, required for their expression so that the pathogenesis could be due to the deleted OXPHOS subunits or to an impaired mitochondrial translation. We have analyzed the mitochondrial genome of a patient presenting with CPEO for single base substitutions and discovered a novel heteroplasmic mutation in the tRNA(Asn) gene at position 5692 that converts a highly conserved adenine into a guanine. This mutation is unique because it is located at the transition of the anticodon loop to the anticodon stem and it leads to an additional base pair, thus reducing the number of loop-forming nucleotides from seven to five. Our findings suggest that CPEO can be caused by a single base substitution in a mitochondrial tRNA gene so that the mitochondrial protein synthesis becomes the rate limiting step in OXPHOS fidelity. PMID- 7980505 TI - Amino-acid responsiveness in beta cell subpopulations with different sensitivity to glucose. AB - Isolated rat beta-cells differ in their individual responsiveness to glucose. The present study examines whether two beta-cell subpopulations with different thresholds for glucose stimulation also differ in their responsiveness to amino acids that are known to stimulate insulin release. The subpopulations were separated by autofluorescence-activated cell sorting using their metabolic responsiveness to 7.5 mM glucose as discriminating parameter. The 7.5 mM glucose responsive and unresponsive subpopulations were perifused in parallel in order to compare their secretory responses to leucine (10 mM) or to arginine (5 mM); responses to glucose were taken as control. Under maximal glucose stimulation (20 mM), the responsive subpopulation released two-fold more insulin than the unresponsive one whereas maximal stimulation with leucine (10 mM) elicited similar first and second phase responses in the two subpopulations. On the other hand, a maximal arginine stimulus (5 mM) amplified release only from glucose activated beta-cells; neither did it correct the differences in glucose-induced insulin release between both subpopulations. These results indicate that rat beta cells exhibit a heterogeneity in secretory responsiveness to glucose but not to leucine, a metabolized secretagogue which can induce release in the absence of glucose. A heterogeneity is also observed in the cellular responsiveness to arginine, and its secretory effect consists of an amplification of glucose activated cells. PMID- 7980507 TI - Protein synthesis is required for the generation of oscillatory current responses in Xenopus oocyte. AB - In Xenopus oocyte, direct activation of G-proteins by AIF4- or injection of inositol 1, 4, 5-trisphosphate evoked Ca(2+)-gated Cl-current responses. The current responses were smooth and not oscillatory when tested immediately after the oocyte was isolated. After hours of incubation, the response became oscillatory. This change was prevented by cycloheximide, a protein synthesis inhibitor. Results indicate that the characteristics of Ca2+ signaling system have changed from not oscillatory to oscillatory with time and protein synthesis was required for this change. PMID- 7980506 TI - Fatty acids and retinoids act synergistically on adipose cell differentiation. AB - Fatty acids and retinoids have been recently reported to act as positive effectors of adipose cell differentiation. Treatment of Ob1771 preadipose cells with selective agonists of retinoic acid receptors (RARs) in the presence of alpha-bromopalmitate, a non-metabolized fatty acid, led to a potent synergy in regard to the differentiation process, as assayed by the activity of glycerol-3 phosphate dehydrogenase. The most potent synergy was observed with compound CD 367, a potent agonist of RARs as well as with compound Am 580, a specific agonist of RAR alpha. Northern blot analysis of poly(A)+ mRNA from cells treated with compound CD 367, alpha-bromopalmitate, or a combination of both agonists, did not show a dramatic effect, if any, on the expression of RAR alpha, RAR gamma, RXR alpha and RXR beta genes. The results are discussed in light of the formation of heterodimers between RARs, RXRs and members of the family of peroxisome proliferator-activated receptors (PPARs). PMID- 7980508 TI - Stimulus-secretion coupling in rat parietal cells is affected by extracellular magnesium. AB - We investigated the effects of extracellular magnesium on stimulus-secretion coupling in isolated rat parietal cells. A high concentration of extracellular magnesium (10 mM) decreased basal and carbachol-stimulated calcium levels, whereas low magnesium levels (0.2 mM) had the opposite effect. The calcium triggered acid secretion was influenced in the same manner. Basal and carbachol stimulated acid secretion could be enhanced by incubation in a buffer of low magnesium concentration, whereas a high magnesium concentration totally suppressed the carbachol-induced acid secretion. These results demonstrate that magnesium plays a modulative role in calcium-dependent stimulus-secretion coupling in rat parietal cells. PMID- 7980509 TI - Divalent cations elevate cytosolic calcium of chick osteocytes. AB - Though it is proposed that osteocytes have several functions in bone metabolism, only limited definite information including results of calcium regulation has been forthcoming. We demonstrate here for the first time that the concentration of divalent cations, such as calcium, nickel and cadmium, directly regulates the cytosolic calcium concentration in osteocytes. PMID- 7980510 TI - Detection of retinoid X receptors using specific monoclonal and polyclonal antibodies. AB - Because of the growing importance of the Retinoid X Receptors (RXR alpha, beta and gamma) in the retinoid acid signalling pathway, we have prepared polyclonal and monoclonal antibodies directed against these proteins. For this purpose, either the whole mouse RXR alpha protein expressed in E.Coli, or synthetic peptides corresponding to amino acid sequences common to all RXRs or unique to RXR alpha, beta or gamma, were used as antigens. Antibodies recognizing either all three RXR types (alpha, beta and gamma) or specific for each RXR type were obtained. The antibodies were characterized by immunocytochemistry, immunoblotting, immunoprecipitation and electromobility shift assay (EMSA). These antibodies allowed us to detect the presence of RXR alpha proteins in mouse embryos and in mouse embryonal carcinoma cells (F9 and P19 cell lines) by immunoblotting, immunoprecipitation and EMSA whereas RXR beta could be detected only by EMSA and RXR gamma could not be detected by any of these techniques. PMID- 7980511 TI - Infrared characterization of nitric oxide bonding to bovine heart cytochrome c oxidase and myoglobin. AB - The stable binding of nitric oxide to both Cu+B and Fe2+a3 in cytochrome c oxidase is shown in infrared spectra. The N-O stretch band for Fe2+a3-NO at 1610 cm-1 is similar to the band for MbNO at 1612 cm-1. The Cu+B-NO band is at 1700 cm 1. Thus, electron donation from metal to NO is greater with Fe2+a3 than Cu+B. However, the affinity for NO is only slightly greater at Fe2+a3 than at Cu+B. In contrast CO binds stably only to Fe2+a3. Infrared spectra of oxidase, myoglobin and hemoglobin NO and CO complexes are consistent with only one stable protein structure at the ligand binding site of nitrosyls and with dynamic multiple protein conformers at carbonyl sites. The binding of NO to both Cu+B and Fe2+a3 of cytochrome c oxidase can contribute to NO cytotoxicity and to the catalysis of NO reduction to N2O and makes possible the effective use of infrared spectroscopy in investigations of Cu as well as Fe at the binuclear O2 reduction sites of oxidases. PMID- 7980512 TI - Selective nuclear transport of mu-calpain. AB - To study nuclear transport of purified calpains in an in vitro system, A431 cells were permeabilized with digitonin, and fluorescein-labeled calpains were introduced under conditions known to facilitate energy-dependent nuclear transport of proteins. Fluorescein-mu-calpain was transported into nuclei in an ATP-dependent fashion. The calpain-specific inhibitor protein, calpastatin, could not block mu-calpain translocation. Fluorescein-calpastatin and fluorescein-m calpain were poorly transported at best. In the presence of rat liver cytosolic factors, accumulation of nuclear mu-calpain was maximum at approximately 1 microM Ca2+, and no transport was observed at 0.3 microM Ca2+. Rat erythrocyte and HeLa cell extracts supported transport in the absence of Ca2+. PMID- 7980513 TI - Recognition of monosialoganglioside (GM3) reconstituted in sphingomyerin and glucosylceramide membranes against wheat germ agglutinin: quantitative analyses by a quartz crystal microbalance. AB - Specific binding of Wheat Germ Agglutinin (WGA) to GM3-containing mixed monolayer at the air-water interface was studied by using a quartz crystal microbalance to know the binding amount and initial binding rate of WGA to GM3. GM3 in the glucosylceramide matrix membrane showed the high recognizability compared to GM3 in sphingomyeline matrix membrane. It is demonstrated that matrix lipids surrounding GM3 regulated the recognition of GM3. PMID- 7980514 TI - The predominant form of fibroblast growth factor receptor expressed by proliferating human arterial smooth muscle cells in culture is type I. AB - Fibroblast growth factors (FGF) and their specific receptors (FGFR) have diverse roles, including induction of proliferation in smooth muscle cells which contributes to restenosis after coronary artery balloon angioplasty. The relative levels of expression of the four major types of FGFR were studied in 13 different human arterial smooth muscle cell isolates. Cell lines were established by the explant technique from intima/media tissue samples obtained from patients undergoing either coronary artery bypass surgery or cardiac transplantation procedures. Expression of FGFR isoforms was analyzed by reverse transcription polymerase chain reaction (RT-PCR) using primers for the conserved tyrosine kinase (TK) domain followed by Southern blotting with TK insert probes unique to each isoform. The data indicate that FGFR I is the major form of FGF receptor mRNA expressed by proliferating human arterial smooth muscle cells. This strongly suggests that it is this type of FGFR that mediates the signal transduction cascade associated with mitogenesis in proliferating human smooth muscle cells. PMID- 7980515 TI - Regulation of osteoclastic acid secretion by cGMP-dependent protein kinase. AB - Nitric oxide (NO) down-regulates osteoclastic activity. The mechanism is unknown, although, in some cells NO acts by stimulating guanylate cyclase which activates cGMP-dependent proteins. We demonstrated cGMP-dependent protein kinase in osteoclasts by immunofluorescence microscopy. Specificity was confirmed by Western blot analysis showing a single 78 kDa band, the size of the Type I isoform, in isolated avian osteoclasts. Osteoclast function centers on HCl secretion at a specialized membrane organelle. We found that purified cGMP dependent protein kinase inhibits ATP-dependent acid transport in reconstituted osteoclast membrane vesicles >90%, while cAMP-dependent kinase catalytic subunit, calmodulin kinase II, or cGMP alone were ineffective. This novel, direct modulation of acid transport by cGMP-dependent kinase and the occurrence of the enzyme in osteoclasts suggest that a mechanism of NO-regulation of bone turnover is via cGMP and cGMP-dependent protein kinase inhibition of HCl transport. PMID- 7980516 TI - A new variant Cu/Zn superoxide dismutase (Val7-->Glu) deduced from lymphocyte mRNA sequences from Japanese patients with familial amyotrophic lateral sclerosis. AB - We have identified a new mutant Cu/Zn superoxide dismutase (SOD1) deduced from the nucleotide sequences of peripheral blood lymphocyte mRNA from Japanese patients with familial amyotrophic lateral sclerosis (FALS). Sequence analysis of reverse transcriptase-initiated PCR amplified mRNA revealed a heterozygosity indicative of one normal allele and one variant allele with a T-->A transversion. This base change led to replacement of valine by glutamic acid at position 7 of 153-residue SOD1 molecule, and produced a new restriction site for Alu I in the exon 1. Restriction fragment length polymorphism analysis confirmed the linkage of this mutation with this type of FALS. Both enzymatic activity and protein of the SOD1 were reduced in red blood cells from the patient. PMID- 7980517 TI - Apigenin induces morphological differentiation and G2-M arrest in rat neuronal cells. AB - Flavonoids are pigments of edible plants. We have recently reported that most flavonoids induce G1 arrest in human cancer cells, and that genistein (an isoflavone) specifically inhibits their cell cycle at G2-M phase. In the present study, apigenin (a flavone) was found to inhibit the proliferation of B104 rat neuronal cells, and flow-cytometric analysis showed that apigenin arrested their cell cycle at G2-M phase. This effect was dose-dependent and reversible when apigenin was removed from the culture medium. Microscopic observation showed that apigenin did not significantly increase the mitotic index compared with the control. Further, apigenin induced morphological differentiation, that is, elongation and arborization of neurites in B104 cells. This is the first report to show that apigenin inhibited the proliferation of malignant tumor cells by G2 M arrest and induced morphological differentiation. PMID- 7980518 TI - Ligand-modulated cross-bridging of microtubules by phosphofructokinase. AB - The interaction of phosphofructokinase and microtubules results in mutual effects: decreases overall activity of the kinase and alters the ultrastructural organization of microtubules. Electron microscopic studies provide direct evidence for the periodical cross-bridges of microtubules by the kinase. 3-4 closely aligned tubules are connected by rows of highly periodic lateral arms about 13 nm long and 12 nm wide. The bundling activity of the enzyme seems to be specific since aldolase, which also interacts with microtubules, does not cross link tubules, but it impedes the binding of the kinase to tubules. ATP, ADP and fructose bisphosphates inhibit the cross-bridges of microtubules by phosphofruktokinase to a different extent and concentration dependent manner. The kinase complexed with specific metabolites inducing distinct conformers does not interact with tubules. Microtubules cross-linked by the kinase became partly resistant to the depolymerizing action of vinblastine. PMID- 7980519 TI - Biosynthesis and processing by phorbol ester of the cells surface-associated precursor form of heparin-binding EGF-like growth factor. AB - Human MDA MB 231 cells were found to synthesize mostly the cell surface associated precursor form of heparin-binding EGF-like growth factor (HB-EGF), a 27-kDa protein. Evidence for this form of HB-EGF included increased fluorescence intensity when cells were analyzed by flow cytometry using anti-HB-EGF antibodies, lack of HB-EGF in conditioned medium, and sensitivity to diphtheria toxin, for which HB-EGF is the receptor. Phorbol ester treatment of cells resulted, within 30 minutes, in loss of cell surface 27 kDA HB-EGF, lack of interaction with anti-HB-EGF antibodies, accumulation of active 21 kDa HB-EGF in conditioned medium, and the acquisition of diphtheria toxin resistance. It was concluded that cell surface-associated HB-EGF is the precursor of a bioactive growth factor, is biologically active as the receptor for diphtheria toxin, and is susceptible to rapid processing. PMID- 7980520 TI - Modification of glutamine synthetase in Streptomyces griseus by ADP-ribosylation and adenylylation. AB - Addition of NH4+ to STreptomyces griseus 2682 cells grown in NO3- containing medium resulted in a rapid decline in glutamine synthetase activity due to covalent modification of the enzyme. The NH4+ promoted inactivation of the enzyme was inhibited by the ADP-ribosyltransferase inhibitor 3-methoxybenzamide. In the presence of ADP-ribosyltransferase activity the purified glutamine synthetase was also inhibited by NAD+ in a concentration-dependent manner. ADP-ribosylation of glutamine synthetase was demonstrated in vitro by showing the incorporation of labeled ADP-ribose from [alpha-32P]NAD+ into glutamine synthetase subunits. Beside ADP-ribosylation, adenylylation of glutamine synthetase was also shown in S. griseus since phosphodiesterase I treatment reactivated the enzyme in crude extracts of NH(4+)-shocked cells. Glutamine synthetase was also inhibited and modified by ATP in crude cellular extracts. These results suggest that in S. griseus 2682 ADP-ribosylation of glutamine synthetase could be an alternative modification to adenylylation to regulate glutamine synthetase activity. PMID- 7980521 TI - Fibronectin-induced cell spreading and down-regulation of 12-lipoxygenase expression in megakaryocytic DAMI cells. AB - During maturation of small immature megakaryocytes to mature platelet producing megakaryocytes the arachidonic acid metabolizing enzyme 12-lipoxygenase is expressed. Here we show that cells of the megakaryocytic cell line DAMI flatten and spread on fibronectin substrate in a way which may be similar to the spreading observed with bone marrow-derived megakaryocytes. The effect on DAMI cell morphology may be attributed to the RGD motif (Arg-Gly-Asp) of fibronectin. Incubation of DAMI cells with fibronectin down-regulated 12-lipoxygenase expression about 85-90%. We discuss the hypothesis that 12-HETE in megakaryocytes may act as a sensor for megakaryocyte attachment to matrix components. PMID- 7980522 TI - Matrilysin is much more efficient than other matrix metalloproteinases in the proteolytic inactivation of alpha 1-antitrypsin. AB - alpha 1-antitrypsin, the primary physiologic inhibitor of human leukocyte elastase, is proteolytically inactivated by several matrix metalloproteinases including interstitial collagenase, stromelysin and 92 kDa gelatinase. In this report, we describe the catalytic effects of matrilysin, a recently identified metalloproteinase, upon alpha 1-antitrypsin. Matrilysin was found to be approximately 30-fold more effective than 92kDa gelatinase, 70-fold more effective than collagenase, and 180-fold more effective than stromelysin. Cleavage of alpha 1-antitrypsin by matrilysin produced two fragments of approximately 50 kDa and 4 kDa. The single cleavage occurred at the Phe352-Leu353 peptide bond, a locus within alpha 1-antitrypsin's active-site loop. These results suggest that apart from its activity against extracellular matrix, matrilysin provides a mechanism for the regulation of leukocyte elastase activity through its capacity to degrade alpha 1-AT. PMID- 7980523 TI - ABL and BCR genes are not imprinted in androgenetic and gynogenetic human tissues. AB - In the translocation leading to the formation of the Philadelphia chromosome, the hallmark of chronic myeloid leukemia (CML), the translocated chromosome 9 (ABL), is of paternal descent whereas chromosome 22 (BCR) is of maternal origin (1). To study possible imprinting of the human ABL and BCR genes, we used human tissues exclusively endowed with their maternally (benign teratoma) or paternally (complete hydatidiform mole) inherited chromosomes. Using the sensitive PCR technique followed by northern blotting, we demonstrate here that ABL and BCR are expressed to a similar extent in androgenetic and gynogenetic human tissues, thus suggesting that ABL and BCR genes are not imprinted in these human tissues. PMID- 7980525 TI - Effects of osmotic changes in extracellular solution on electrical activity of mouse pancreatic B-cells. AB - The influence of changes in the osmolarity of the extracellular solution on electrical activity of mouse pancreatic B-cells was studied with intracellular microelectrodes. In the presence of 15 mmol/l glucose the membrane potential of B cells oscillates. A reduction of the osmolarity by 40 mosmol/l caused a small temporary hyperpolarization in six out of eight cells. After 2 to 3 min electrical activity was increased in all cells. However, this effect was also transient. 5 to 8 min after onset of exposure to hypotonic solution the cells repolarized again and electrical activity decreased. Increasing the osmolarity of the extracellular solution by 40 mosmol/l led to a sustained and reversible depolarization of the membrane potential. However, the electrical activity was transiently suppressed. The changes in electrical activity observed in hypotonic solution might explain the previously described transient rise in insulin secretion provoked by osmotic cell swelling. PMID- 7980524 TI - The alpha PDGFR tyrosine kinase mediates locomotion of two different cell types through chemotaxis and chemokinesis. AB - To determine the capability of alpha PDGFR to couple with chemotactic signaling, we established 32D cells expressing wild type alpha PDGFR (alpha RWT), a kinase defective mutant of alpha PDGFR (alpha R627R), or wild type beta PDGFR (beta RWT). Using a modified Boyden chamber, we showed that PDGF induced significant cell migration of 32D cells expressing alpha RWT or beta RWT, but not of those expressing alpha R627R. Furthermore, the cell migration was largely reduced in each case when the same concentration of PDGF was present in both chambers, suggesting that cell migration observed in 32D expressing alpha RWT is mainly due to alpha PDGFR-mediated chemotaxis. Consistent with these results, PDGF-AA induced significant cell migration of NIH3T3 fibroblasts, which was markedly blocked by the presence of excess neutralizing polyclonal antibody to PDGF-AA. These results provide evidence that alpha PDGFR kinase activity is essential for mediating ligand-induced chemotactic and chemokinetic responses in two different cell types. PMID- 7980526 TI - Cloning and expression of recombinant human growth/differentiation factor 5. AB - The complete amino acid sequence of human Growth/differentiation factor 5 (huGdf5), a new member of the TGF-beta superfamily, has been determined through initial degenerate PCR and subsequent cloning and nucleotide sequencing of genomic DNA and cDNA encoding the precursor and flanking regions. The huGdf5 gene consists of only two coding exons. The protein is highly homologous to its murine equivalent, particularly the mature part which differs only by one amino acid. Expression in HuTK- cells using recombinant vaccinia virus revealed the expected processed dimeric mature protein. Antibodies against huGdf5 were raised in chicken. PMID- 7980527 TI - Autocrine inhibition of the epidermal growth factor receptor by intracellular expression of a single-chain antibody. AB - A gene encoding a single-chain antibody which specifically binds the human epidermal growth factor (EGF) receptor has been constructed and expressed intracellularly. The single-chain antibody is derived from monoclonal antibody 225 which competes with EGF for binding to the extracellular domain of the receptor. The single-chain antibody was provided with a signal peptide to direct it to the secretory pathway and was expressed in EGF receptor transformed NIH/3T3 fibroblasts. EGF induced activation of its receptor was reduced in these cells. In addition, EGF-induced anchorage-independent growth of the cells was inhibited. The data suggest that the single-chain antibody functions in an autocrine fashion to inhibit the activity of the EGF receptor. PMID- 7980528 TI - Modulators of oxidized LDL-induced hyperadhesiveness in human endothelial cells. AB - The adherence of monocytes to the endothelium is an early event in atherogenesis. Our previous studies have demonstrated that oxidized LDL induced U937 cells endothelial interactions and that HDL prevented oxidized LDL effects. Here, we provide evidence that treatment of endothelial cells with the anti-inflammatory agent indomethacin abolished oxidized LDL as well as interleukin 1- and lipopolysaccharide-stimulated U937 adhesion. It is noteworthy that HDL, which is known to be protective against atherosclerosis, was effective only in negating U937 adhesion induced by oxidized LDL, while it did not affect interleukin 1- and lipopolysaccharide-induced hyperadhesiveness in endothelial cells. Since indomethacin inhibits cyclooxygenase which is the key enzyme in the synthesis of prostanoids, we have studied the effect of oxidized LDL on the expression of cyclooxygenase type 2 and demonstrated that oxidized LDL induces a sustained increase in the expression of cyclooxygenase mRNA. PMID- 7980529 TI - Transforming growth factor-beta 1 regulates the expression of ryanodine-sensitive Ca2+ oscillations in cardiac myocytes. AB - Factors which regulate sarcoplasmic reticulum (SR) gene expression are largely unknown. We investigated whether Transforming Growth Factor-beta 1 (TGF-beta 1) plays a role in the maintenance of Ca2+ handling mechanisms in isolated neonatal rat cardiomyocytes. Myocytes cultured in the presence of serum were found to beat continuously and undergo spontaneous Ca2+ oscillations whereas in the absence of serum the cells lost the ability to undergo cyclical Ca2+ oscillations. The oscillations were restored when serum-free medium was supplemented with TGF-beta 1. Both caffeine-induced Ca2+ elevations and the inhibitory effect of ryanodine on spontaneous activity were also dependent on the continued presence of TGF-beta 1; in its absence these indices of SR function were severely compromised. TGF beta 1 therefore appears to play a critical role in the maintenance of Ca2+ oscillations in the heart by regulating the expression of the ryanodine-sensitive Ca2+ release mechanism. PMID- 7980530 TI - Characterization of contractile endothelin and angiotensin receptors in human resistance arteries: evidence for two endothelin and one angiotensin receptor. AB - Endothelin-1 (ET-1) and angiotensin II (AII) are potent vasoconstrictor hormones which regulate tissue perfusion and blood pressure. We pharmacologically characterized endothelin and angiotensin receptors mediating contractions of human mammary resistance arteries in myographs for isometric tension recording. ET-1 caused potent contractions. The concentration response curve was shifted to the right by ETA antagonist FR 139317, but a high sensitivity, low efficacy component remained. After incubation with ETB agonist sarafotoxin (S6c) this component of the concentration response curve resistant to FR 139317 disappeared. The ETA/ETB-receptor antagonist bosentan shifted the entire concentration response curve to the right. AI and AII caused marked contractions. The effects of AI were reduced by the ACE inhibitor benazeprilat, while those of AII were prevented by valsartan, an AT1 antagonist. In summary, in human resistance arteries, contractions to ET-1 are mediated by ETA- and ETB-receptors while those to AII are exclusively mediated by AT1-receptors. PMID- 7980531 TI - Calcium modulates the cyclin D1 expression in a rat parathyroid cell line. AB - We have used a rat epithelial parathyroid cell line (PT-r) to study the expression and regulation of D-type cyclins. In PT-r cells the cyclin D1 gene is the most abundantly expressed, being transcribed in at least two mRNAs whose levels oscillate during the cell cycle. We also screened a cDNA library prepared from PT-r cells with the human cyclin D1 probe and isolated its rat homologue. Cyclin D2 and D3 mRNAs are both represented in PT-r cells but the former one is only barely detectable. Moreover, the oscillation of cyclin D3 transcript is slightly delayed when compared to cyclin D1 and D2. Since extracellular calcium inhibits parathyroid cell proliferation, we looked for the effect of the ion on the expression of cyclin D genes in PT-r cells. Increasing amounts of calcium in the incubation medium reduced the expression of rat cyclin D1 and D2. The effect appears to be cell-specific and probably mediated through the inhibition of mitogenic signalling pathways. PMID- 7980532 TI - Identification of functional cysteine residues in human galactosyltransferase. AB - The functions of the five cysteine residues in human galactosyltransferase were investigated using site-directed mutagenesis to determine the location of the disulfide bond as well as the role of the sulfhydryl groups. The enzyme remains active when three of its cysteine residues at positions 171, 264 and 340 are mutated to serine separately. However, enzymatic activity is lost when either cysteine-129 or cysteine-245 is replaced with serine. The loss of GT activity suggests that these two cysteine residues form a disulfide bond. The three active mutated enzymes were studied kinetically. The kinetic constants of the enzymes with cysteine-171 or cysteine-264 replaced with serine are not significantly different from those of GT that does not have these substitutions. When cysteine 340 was mutated, however, the kinetic constant for UDP-galactose increased about 30 fold, while that for N-acetylglucosamine and Mn2+ remained unchanged. In addition, sulfhydryl inhibition studies reveal that cysteine-340 is the only cysteine residue that reacts with the sulfhydryl reagents. These results indicate that cysteine-340 may be involved in the binding of UDP-galactose. PMID- 7980534 TI - Glucose-6-phosphatase gene expression and activity are modulated in hemorrhagic shock: evidence for a new heat-sensitive activator. AB - Decreased hepatic fructose 2,6-bisphosphate levels were observed in the early phase of hemorrhagic shock. The lower sugar bisphosphatae level was a result of increased phosphoenolpyruvate levels and decreased glucose-6-phosphate and fructose-6-phosphate levels. The decreased glucose-6-phosphate levels correlated with increased activity of liver glucose-6-phosphatase and a concomitant 2.5-fold increase in glucose-6-phosphatase mRNA abundance. In addition, protein-free filtrate from hemorrhagic shock rats, but not from control rats, increased glucose-6-phosphatase activity. However, when control and hemorrhagic shock protein-free filtrates were heated, they both increased the glucose-6-phosphatase activity of the respective microsomes to the same extent. It is concluded that the early hyperglycemic phase of hemorrhagic shock is due to enhanced glucose-6 phosphatase gene expression and activity and the generation of a heat sensitive activator of the enzyme. PMID- 7980533 TI - The tumor protein MAGE-1 is located in the cytosol of human melanoma cells. AB - The MAGE-1 protein has been localized to the cytosol of human melanoma culture cells (MZ2-MEL.43) by subcellular fractionation. Its distribution between nuclear, mitochondrial, microsomal and cytosolic fractions was established by SDS PAGE and immunoblotting with a rabbit antiserum and compared to that of markers for the main cell compartments. The immunoreactive material was recovered in the cytosolic fraction as a polypeptide migrating at 42 kDa, which has been further identified as the MAGE-1 protein because it comigrates with the product of cell free transcription-translation of the MAGE-1 cDNA. Location to the cytosol was confirmed by immunofluorescence microscopy. PMID- 7980535 TI - Delayed processing of the insulin proreceptor by hepatocytes from diabetic rats. AB - The effect of diabetes on insulin receptor processing was assessed in rat hepatocytes, 2-4 weeks after the induction of diabetes with streptozotocin. Isolated hepatocytes from control and diabetic rats were labelled for 30 min with [35S]methionine in methionine-free medium and chased with complete medium for 1-3 hrs. Solubilized cell extracts were immunoprecipitated with a site-specific anti insulin receptor antibody, proteins were separated by electrophoresis and labelling quantified following autoradiography. After 1 hr chase, only the insulin proreceptor was labelled in both groups. After 3 hrs, the ratio of labelled proreceptors to labelled insulin receptors was 0.57 +/- 0.063 in controls and 1.33 +/- 0.24 in hepatocytes from diabetic rats. Insulin added in vitro did not affect transit time. Delayed processing of the insulin proreceptor may reflect altered N-glycosylation and may also involve other glycoproteins. PMID- 7980536 TI - Modulation of calcium current density by intracellular calcium in isolated guinea pig ventricular cardiomyocytes. AB - This study describes quantitatively the relation between L-type calcium current (ICa) density and resting cytosolic free calcium concentration ([Ca2+]i) in isolated guinea pig ventricular cardiomyocytes. ICa was measured simultaneously with [Ca2+]i at 22 and 35 degrees C using the whole-cell patch-clamp method in combination with the Fura-2 ratio-fluorescence technique. At 22 degrees C, the increase in [Ca2+]i upon replacing external Na+ with tetraethylammonium resulted in a monotonic decrease in ICa density. Half-maximal inhibition of ICa density occurred at a [Ca2+]i value (K0.5) of 60 +/- 17 nM (mean +/- S.D., n = 59). At 35 degrees C, with a holding potential of -80 mV, a similar relation between [Ca2+]i and ICa was observed (K0.5 of 62 +/- 12 nM, n = 34). When the cells were depolarized from -40 mV, however, the initial decrease in ICa density with increasing [Ca2+]i was usually followed by transient stimulation (< or = 2-fold), which was again overcome by inhibition. Stimulation was not observed in the presence of broad spectrum protein kinase inhibitors. These data suggest that Ca2+i-dependent facilitation of cardiac ICa is mediated by a temperature sensitive enzymatic pathway that ends in voltage-dependent phosphorylation of Ca2+ channels. PMID- 7980537 TI - GM2 activator protein expression in mouse tissues. AB - The GM2 activator protein is an essential cofactor of hexosaminidase A in the degradation of GM2 ganglioside and it is responsible for the variant AB of GM2 gangliosidosis in man. In this study GM2 activator protein and its mRNA were determined in different mouse tissues. It was found that this protein is expressed mostly in the spleen and testis followed by brain and kidney which represent the main source in man. It is also interesting that in mouse testis there is a higher expression of the alpha subunit of hexosaminidase, thus suggesting a relationship between alpha subunit and GM2 activator protein. Furthermore the results indicate that the expression of GM2 activator protein is regulated, at least in part, at the transcriptional level. PMID- 7980538 TI - HSP 90 alpha and HSP 90 beta genes are present in the zebrafish and are differentially regulated in developing embryos. AB - We have employed a polymerase chain reaction-based cloning strategy to demonstrate that both hsp 90 alpha and hsp 90 beta genes are present in the zebrafish. The fact that zebrafish represents the most primitive vertebrate in which hsp 90 genes have been isolated to date has allowed us to determine that the duplication event which generated the hsp 90 alpha and hsp 90 beta genes occurred shortly before the emergence of the teleosts from the rest of the vertebrate lineage. In expression studies using Northern blot analysis, hsp 90 beta mRNA was found to be present at control temperatures throughout normal embryonic development whereas hsp 90 alpha mRNA was barely detectable. Upon heat shock, hsp 90 alpha mRNA levels increased dramatically in all developmental stages examined. The levels of hsp 90 beta mRNA increased 2-3 fold during heat shock of early stage embryos. Thus, the hsp 90 alpha gene is strongly upregulated during heat shock in zebrafish embryos whereas expression of the hsp 90 beta gene appears to be weakly induced. PMID- 7980539 TI - Reversal of valproic acid-associated impairment of carnitine uptake in cultured human skin fibroblasts. AB - Much attention has focussed on the role of valproic acid induced secondary carnitine deficiency in predisposing children to life-threatening hepatotoxicity and a Reye-like syndrome. One mechanism by which valproic acid therapy induces serum and tissue depletion of carnitine is through inhibition of plasmalemmal carnitine uptake. In cultured control human skin fibroblasts, this effect is directly proportional to the duration of exposure and concentration of valproic acid; the maximal effect of valproic acid exposure time is achieved by 14 days, beyond which there appears to be no additional significant effect (1). To determine whether this effect is reversible, we preincubated control fibroblasts with varying concentrations (0-1700 mumol/L) of valproic acid for 14 days, washed the fibroblasts free of valproic acid, and then continued the fibroblast growth in valproic acid-free medium for periods of 4 hours to 14 days. The fibroblasts were subsequently incubated with fixed carnitine concentrations of 50 mumol/L (normal physiological concentration), 20 mumol/L (as seen in secondary carnitine deficiency disorders), or 5 mumol/L (as seen in the homozygous plasma membrane carnitine transporter defect) and the carnitine uptake was determined. The inhibitory effect of valproic acid on carnitine uptake was completely reversed, for all 3 carnitine concentration conditions, following > or = 5 days of growth in valproic acid-free medium. PMID- 7980541 TI - ADP-ribosylation of heterogeneous ribonucleoproteins in HeLa cells. AB - Poly and mono (ADP-ribosyl)transferases catalyze the transfer of ADP-ribose from nicotinamide adenine dinucleotide (NAD) to acceptor proteins. Protein substrates of ADP-ribosylation reactions were investigated in human cervical carcinoma (HeLa) cells in the exponential phase of growth. Permeabilized cells were incubated with [32P]-NAD and ADP-ribosylated proteins were detected by two dimensional polyacrylamide gel electrophoresis (2D-PAGE) and autoradiography. Microsequencing of two coomassie blue-stained proteins corresponding to 32P labeled proteins on autoradiographs revealed sequence identity with heterogeneous ribonucleoproteins (hnRNPs) A1 and A2/B1, consistent with the isoelectric points, molecular sizes, and 2D-PAGE map locations of these proteins. ADP-ribosylation of hnRNPs may thus serve to modulate the activity of these proteins in the nucleus. PMID- 7980540 TI - Sequence of the gene, amoB, for the 43-kDa polypeptide of ammonia monoxygenase of Nitrosomonas europaea. AB - The sequence for the 3' portion of amoB, a gene encoding a 43-kDa polypeptide component ammonia monooxygenase of Nitrosomonas europaea, is presented. The derived polypeptide has no homology with other known proteins. AmoA and amoB are the only open reading frames in the putative amo operon. PMID- 7980542 TI - The metabolic pathway generating p3, an A beta-peptide fragment, is probably non amyloidogenic. AB - The Alzheimer a beta amyloid precursor protein is metabolized by at least two secretory pathways. One generates the A beta peptide and the other a N-terminally truncated A beta fragment termed p3 that is considered non-amyloidogenic. However, direct evidence is missing. We have undertaken to synthesize and purify p3. Pure p3 polymerizes in vitro, forming a lattice with an ultrastructure distinct from the linear fibrils of A beta. In contrast to amyloid, polymerized p3 does not bind thioflavine T. It is therefore concluded that amino acids in the N-terminal part of the A beta molecule are required for formation of typical amyloid fibrils and that the metabolic pathway generating p3 probably is non amyloidogenic PMID- 7980543 TI - 8-Amino-2'-deoxyadenosine: 2'-deoxythymidine base pairing: identification of novel reverse Hoogsteen mode in solution. AB - A novel reversed Hoogsteen mode is observed for the base-pairing of 8-amino-2' deoxyadenosine with 2'-deoxythymidine in low dielectric solvent. The results may have important significance for designing novel DNA duplexes and triplexes incorporating 8-amino-dA. PMID- 7980544 TI - Cobalt stimulates the expression of vascular endothelial growth factor mRNA in rat cardiac cells. AB - We have previously demonstrated that an exposure of rat cardiomyocytes to anoxia induces the expression of mRNAs coding for vascular endothelial growth factor (VEGF). The action of anoxia was mimicked by Co, Ni and Mn. The actions of Co and of anoxia were not additive and did not involve AP-1 binding sites. Experiments using actinomycin D and cycloheximide indicated that VEGF mRNA levels in cardiac cells are regulated both at transcriptional and post transcriptional levels. It is concluded that an oxygen sensing mechanism is present in cardiac cells and controls the expression of VEGF mRNAs. It may be important for the neovascularization of ischemic myocardium. PMID- 7980545 TI - Characterization of human B cell proteins binding specifically to uveitopathogenic peptide 1169-1191 of bovine IRBP. AB - Peptide 1169-1191 is a major uveitopathogenic determinant of bovine Interphotoreceptor Retinoid Binding Protein (IRBP) in Lewis rats. Previously, we identified two proteins with approximate molecular masses of 72 and 74 kDa and one with a molecular mass of 40 kDa from B cells of naive Lewis rats and EBV transformed B cells from a human patient with ocular Behcet's disease that bind to bovine IRBP peptide 1169-1191. In this study, we have partially characterized these proteins. The two proteins with molecular masses 72 and 74 kDa belong to the HSP 70 family of proteins and the 40-kDa protein is actin. PMID- 7980546 TI - 1,25-Dihydroxyvitamin D3 effects in rat kidney: regulation of protein phosphorylation. AB - This study tested the hypothesis that 1,25-dihydroxyvitamin D3 treatment alters the pattern of protein phosphorylation in rat kidney. Treatment with 1,25 dihydroxyvitamin D3 (100 ng/day s.c. x 7d) in vitamin D-deficient rats markedly decreased phosphorylation of a particulate protein (91 +/- 0.6 kDa, n = 9) and moderately increased phosphorylation of a cytosolic protein (108 +/- 0.8 kDa, n = 9) in the kidney. The decreased phosphorylation of the 91-kDa particulate protein showed a graded dose response (0-200 ng/day), as did the more moderate increase in phosphorylation of the 108-kDa cytosolic protein. In conclusion, this study has provided evidence that 1,25-dihydroxyvitamin D3 plays an important role in the regulation of protein phosphorylation in rat kidney and adds these biochemical events to the growing list of 1,25-dihydroxyvitamin D3 effects in this poorly understood target tissue. PMID- 7980547 TI - Characterization of Ca(2+)-ATPase in rod outer segment disk membranes. AB - The Ca(2+)-pump isolated in rod outer segment disk membranes as aspartylphosphate intermediate E-P has been characterized: the 100 kDa phosphoprotein was completely inhibited by thapsigargin, was not sensitive to digestion by calpain, and displayed a tryptic digestion pattern with the formation of two autophosphorylatable fragments of about 55 and 35 kDa. These results are typical of the calcium pumps of sarcoplasmic or endoplasmic reticulum calcium and differ from those of plasma membrane, such as the Ca(2+)-ATPase of the red blood cells, here shown as controls. The physiological role of calcium pump in disk membranes of vertebrate photoreceptors is discussed in terms of intracellular calcium buffering. PMID- 7980548 TI - Analysis of short novel human papillomavirus sequences. AB - Consensus primer mediated PCR protocols have the potential to amplify previously uncharacterized human papillomavirus (HPV) genotypes. In a study on 500 cervicovaginal samples, we amplified four sequences (L1AE 1 to L1AE 4) that failed to hybridize to any of the available HPV type-specific oligonucleotide probes. Nucleotide sequencing revealed that the sequences were derived from the L1 region of hitherto unsequenced genotypes. Comparison of phylogenetic trees based on the amplified L1 sequences with E6-derived phylogenetic trees resulted in the identification of L1AE 1 and L1AE 2 as putative novel HPV PCR genotypes. L1AE 1 was related to HPV 39, whereas L1AE 2 was related to HPV 51. The L1AE 3 and L1AE 4 sequences occupied L1-phylogenetic branches equivalent to the positions of HPV 66 and HPV 61, respectively, in an E6-phylogenetic tree. PMID- 7980549 TI - Secretion of immunoreactive corticotropin releasing factor and adrenocorticotropic hormone by T- and B-lymphocytes in response to cellular stress factors. AB - The ability of human lymphocytes and mouse splenocytes to secrete corticotropin releasing factor (CRF) in response to hyperthermia, hyperosmolarity and hypoxia has been shown. Both human T- and B-lymphocytes appear to have this ability. E. coli lipopolysaccharide and concanavalin A can stimulate CRF secretion by B- and T-lymphocytes, respectively, whereas hydrocortisone inhibits the CRF secretion induced by any agent tested. Adrenocorticotropic hormone (ACTH) secretion in response to hyperthermia, hyperosmolarity and hypoxia was demonstrated also, and this secretion could be inhibited by anti-CRF antibodies and by hydrocortisone. We demonstrate that CRF could provide a necessary link between external stimuli such as cellular stress factors and ACTH secretion by immunocytes leading to corticosteroid production and, subsequently, to non-specific defence reaction of the organism. We also describe a model designed to explain the results obtained. PMID- 7980550 TI - Rapid isolation of G alpha 13 from bovine brain membranes: supportive effect of ethylene glycol. AB - G13 belongs to the G12-subfamily of heterotrimeric regulatory G-proteins. Employing specific antibodies, we isolated G alpha 13 from bovine brain by a four step purification protocol combining conventional and affinity chromatography. The use of ethylene glycol as a protective agent influenced the elution properties of G alpha 13 markedly. Only in the presence of ethylene glycol (30% v/v) a clear separation of G alpha 13 from other G-proteins was achieved during the initial anion exchange chromatography. This allowed isolation of G alpha 13 by subunit exchange chromatography on beta gamma-agarose. G alpha 13 was only released from immobilized beta gamma-dimers via activation by AMF but not by GTP gamma S, pointing to a poor basal nucleotide exchange of this protein. In contrast, N-terminally truncated G alpha 13 did not bind to immobilized beta gamma-dimers. PMID- 7980551 TI - The aminoterminus of c-Raf-1 binds a protein kinase phosphorylating Ser259. AB - The kinase negative aminoterminal domain of c-Raf-1 expressed as glutathione S transferase fusion protein was phosphorylated in vitro after treatment with lysates from A431 cells and subsequent in vitro protein kinase assay. This phosphorylation was independent of stimulation of the cells with EGF; it occurred exclusively on serine and was mapped to Ser259. The identical site of c-Raf-1 was phosphorylated in A431 cells by metabolic labelling in vivo. The kinase binding domain was mapped by various GST-Raf deletion mutants to c-Raf-1 aminoacid residues 181 to 255. PMID- 7980552 TI - Selection of peptides with affinity for single stranded DNA using a phage display library. AB - A hexapeptide phage library was used to affinity select peptides which interact with single stranded heptaoligonucleotides consisting of cytosine (oligo-C). Selections were performed in two different buffer systems, 50 mM 2[N Morpholino]ethanesulphonic acid(MES)-buffer, pH 5.5, and 50 mM Tris(hydroxymethyl)-aminomethane, 150 mM NaCl, pH 7.5, respectively. Selection was more successful in 50 mM MES-buffer and three clones with affinity for oligo C were further investigated. The peptides, Pro-Pro-Pro-Leu-Tyr-Phe, Arg-Phe-Cys Asp-Thr-Ser and Arg-Ser-Arg-Leu-Ile-Trp, all interacted more strongly with oligo C compared to the original peptide phage library and wildtype phage. The selected clones also showed different specificity in the interaction with oligo-C, -G, -A and -T. PMID- 7980553 TI - Characterization of ATP-sensitive potassium channels in intestinal, cholecystokinin-secreting cells. AB - In the present study, the electrophysiologic properties of ATP-sensitive potassium channels were evaluated in an intestinal, cholecystokinin-secreting cell line (STC-1). Channels were operative under basal conditions and, in cell attached membrane patches, channel activity was decreased by glucose or disopyramide, agents which classically inhibit ATP-sensitive potassium channels. Channel activity was increased by the KATP channel opener, diazoxide. Intestinal ATP-sensitive potassium channels appear to behave in a similar manner to those found in cardiac and pancreatic beta cells. PMID- 7980554 TI - Identification of tissue-specific protein binding domains in the 5'-proximal regulatory region of the rat mitochondrial brown fat uncoupling protein gene. AB - The 5' proximal region of the rat uncoupling protein gene, extending from -611 to +110, contains cis-acting elements involved in cell-specificity and cAMP regulation of transcription. DNAse I footprinting of this region was performed using protein extracts from brown adipose tissue and liver nuclei. Nine protein binding domains were observed using nuclear proteins from both tissues. They include the elements for basal promoter activity (TATA and CCAAT elements), a cAMP-responsive element, two C/EBP binding sites and three unidentified DNA protein binding domains sharing a common GCCCCT sequence. A purine rich region at -402/-362 was observed to bind proteins abundant in liver but scarce in brown adipose tissue nuclei. A single region at -512/-487 was identified as the only element that binds nuclear proteins present in brown adipose tissue but absent in liver. This putative tissue-specific element in the uncoupling protein gene contains a sequence identical to mammalian or viral gene elements that bind members of the ETS family of transcription factors. PMID- 7980555 TI - Src kinase tyrosine phosphorylates PTP1C, a protein tyrosine phosphatase containing Src homology-2 domains that down-regulates cell proliferation. AB - PTP1C is a non-transmembrane-type protein-tyrosine phosphatase and contains two Src homology-2 (SH2) domains. PTP1C was tyrosine-phosphorylated in SR-3Y1, a v Src-transformed rat fibroblast cell line. Tyrosine phosphorylation of PTP1C was more prominent when PTP1C was overexpressed in SR-3Y1 cells. PTP1C lacking SH2 domains was also tyrosine-phosphorylated in SR-3Y1 cells, indicating that SH2 domains of PTP1C are not required for tyrosine phosphorylation of PTP1C by v-Src kinase. V-Src kinase catalyzed the phosphorylation of PTP1C in a cell-free system. The growth rate of SR-3Y1 was reduced by the expression of PTP1C in the low-serum medium. Furthermore, overexpression of PTP1C suppressed the anchorage independent colony formation of SR-3Y1 cells. These results suggest that PTP1C is a direct target for v-Src kinase and may down-regulate the proliferation of cells. PMID- 7980556 TI - Involvement of androgen-induced growth factor (FGF-8) gene in mouse embryogenesis and morphogenesis. AB - Androgen-induced growth factor (AIGF/FGF-8) has purified from a mouse mammary carcinoma cell line and its cDNA cloning revealed that AIGF is the eighth member of the fibroblast growth factor family. To clarify a biological role of FGF-8, Northern blot analysis of various adult tissues was carried out, but no expression was found. However, whole mount in situ hybridization of 7.5- to 14.5 day gestation (E7.5-14.5) embryos revealed six predominant expression domains: [1]primitive streak region (E7.5-9.75); [2]midbrain-hindbrain border (E8.0-10.5); [3]rostral forebrain (E8.0-10.5); [4]limb ectoderm and apical ectodermal ridge (E9.25-13.5); [5]nasal placode and epithelium (E9.5-12.5); and [6]branchial arch ectoderm (E8.5-11.5). The embryonic expression pattern suggests a unique role of FGF-8 in mouse development, especially in gastrulation, brain development, and limb and facial morphogenesis. PMID- 7980557 TI - Organization and expression of the mouse spot35/calbindin-D28k gene: identification of the vitamin D-responsive promoter region. AB - Spot35/calbindin-D28k is transcriptionally induced by 1,25-dihydroxyvitamin D3 in the intestine and kidney but not the brain. The structural organization of the mouse calbindin-D28k gene has now been determined and its transcriptional activation examined. Two direct repeat motifs homologous to other vitamin D responsive elements were identified at positions -2295 to -2281 and -1160 to 1146. Undirectional deletion analyses of the 5' flanking region indicated that the sequence between -1339 and -1038 conferred vitamin D sensitivity on a reporter construct. Furthermore, the proximal (AGGTGAtgaAAGTCA), but not the distal (AGGTGAacaGGTTCA), direct repeat enhanced 1,25(OH)2D3-stimulated transcription in an orientation-dependent manner when placed upstream of the heterologous SV40 promoter. In conclusion, the proximal direct repeat plays a critical role in mediating the vitamin D-induced expression of calbindin-D28k in the kidney. PMID- 7980558 TI - Antioxidant, gallic acid, induces apoptosis in HL-60RG cells. AB - Gallic acid, a naturally occurring plant phenol with antioxidative activity, was found to induce cell death in promyelocytic leukemia HL-60RG cells, although many antioxidants are well known to protect the cell from oxidative stress. Morphological and biochemical studies indicated that the gallic acid-induced cell death is apoptosis. Flow cytometric analysis revealed that the apoptosis was not triggered at a specific phase of the cell cycle and that 2 h exposure of gallic acid to HL-60RG cells was enough to induce apoptosis. The inhibitory assay suggested that gallic acid-induced cell death was mediated by reactive oxygen species such as hydrogen peroxide, superoxide anion in addition to Ca2+ ion, calmodulin-dependent enzymes. Structure-activity analysis suggests that gallic acid induces apoptosis in HL-60RG cells, depending on its distinctive feature derived from the structure but not on its antioxidative activity. PMID- 7980559 TI - Androgens directly stimulate mineralization and increase androgen receptors in human osteoblast-like osteosarcoma cells. AB - 5 alpha-Dihydrotestosterone (DHT), an active form of testosterone, was shown to stimulate the mineralization of osteoblasts in a time- and dose-dependent manner in vitro in the presence of inorganic phosphate, as well as transforming growth factor beta and 1 alpha, 25 dihydroxyvitamin D3. However, DHT, stimulated the mineralization by a different mechanism from that of transforming growth factor beta and 1 alpha, 25 dihydroxyvitamin D3. We found that DHT increased the number of androgen receptors. These findings suggest that androgens directly stimulate mineralization in osteoblasts associated with an increase in the number of their receptors. PMID- 7980560 TI - Substitution of the ISP alpha subunit of biphenyl dioxygenase from Pseudomonas results in a modification of the enzyme activity. AB - We have constructed a hybrid multicomponent dioxygenase gene cluster in which the bphA1 gene, coding for ISP alpha subunit of biphenyl dioxygenase from Pseudomonas pseudoalcaligenes KF707, has been replaced by the bedC1 gene encoding the corresponding subunit of benzene dioxygenase from P. putida ML2. Escherichia coli cells containing the chimeric dioxygenase acquired the novel capability of producing indigo from indole. Furthermore, when compared to biphenyl dioxygenase, the hybrid dioxygenase enzyme was half as active towards benzene but exhibited only 4% activity when biphenyl was the substrate. The results implicate the ISP alpha subunit to be involved in substrate specificity and activity of the dioxygenase enzyme. PMID- 7980561 TI - Modulation of responses to TGF-beta by 1, 25 dihydroxyvitamin D3 in MG-63 osteoblastic cells: possible involvement of regulation of TGF-beta type II receptor. AB - The effect of TGF-beta 1 on the expression of alkaline phosphatase (ALPase) activity was examined during osteoblastic cell line (MG-63) differentiation induced by 1,25-dihydroxyvitamin D3 (1,25D3). TGF-beta 1 and 1,25D3 were found to enhance ALPase activity. However, preincubation of the cells with 1,25D3 transiently abolished the effects of TGF- beta 1. Kinetics of the complex responses to TGF- beta 1 and 1,25D3 were found to correlate well with that of the expression level of type II receptor for TGF- beta. These results suggest that 1,25D3 may regulate the cellular responses to TGF- beta 1 in part via regulation of functional receptor for TGF- beta. PMID- 7980562 TI - Peptides corresponding to the region adjacent to His-94 in the small subunit of cytochrome b558 inhibit superoxide generation in a cell-free system from human neutrophils. AB - Synthetic peptides corresponding to the region adjacent to His-94 in the small subunit of cytochrome b558 inhibited superoxide generation in a cell-free system. The shortest sequence that gave a half inhibitory concentration (IC50) lower than 50 microM was TRNYYVRAVL. Substitution of alanine for any of two tyrosine or central valine residues markedly increased IC50, thereby indicating that these residues are critical for the activity. Since the inhibition was observed when the peptide was added to the system before but not after the stimulation with sodium dodecylsulfate, the peptides seem to interact irreversibly with the cytochrome molecule and hinder electron transport or alternatively to interfere with the association between cytochrome b558 and cytosolic components. PMID- 7980563 TI - Isolation, sequence and expression of a novel mouse brain cDNA, mIA-2, and its relatedness to members of the protein tyrosine phosphatase family. AB - This study describes the isolation of a putative transmembrane protein tyrosine phosphatase (PTP), mIA-2, from a mouse brain cDNA library. The cDNA encodes 979 amino acids containing a unique extracellular domain and a single intracellular catalytic domain. Expression of mIA-2 was found primarily in the central nervous system and in neuroendocrine cells. The sequence shares a high degree of homology with its human counterpart (92% identity), especially in the intracellular domain, which shows 99.3% identity between the two species. In both human and mouse IA-2, several substitutions were found in the highly conserved regions including an Ala to Asp substitution in the core sequence. Bacterial expression of a glutathione S-transferase fusion protein showed that mIA-2 had no enzyme activity with conventional substrates such as Raytide, myelin basic protein, angiotensin, RR-src and pNpp. When tested with the total tyrosine-phosphorylated cellular proteins isolated on an anti-phosphotyrosine antibody column, it also showed little, if any, enzyme activity. These findings suggest that mIA-2 is a new member of the transmembrane PTP family that either has very narrow substrate specificity perhaps requiring post-translational modification for enzyme activity or has a still unknown biological function. PMID- 7980564 TI - Hepatic metabolism of chloral hydrate to free radical(s) and induction of lipid peroxidation. AB - Metabolism of chloral hydrate by male B6C3F1 mouse liver microsomes generates free radical intermediate(s) as evidenced by electron spin resonance spectroscopic analysis. The subsequent induction of endogenous lipid peroxidation was shown by analysis of the resulting products with high-pressure liquid chromatography. Chloral hydrate was found mutagenic in Salmonella typhimurium strain TA104. Both lipid peroxidation and mutagenicity were efficiently inhibited by free radical scavengers, alpha-tocopherol and menadione. PMID- 7980565 TI - Syndecan-1 gene expression in isolated rat liver cells (hepatocytes, Kupffer cells, endothelial and Ito cells). AB - Normal liver contains mainly heparan sulfate proteoglycans. To determine which liver cells are able to express syndecan-1 RNA, hepatocytes, endothelial, Kupffer and Ito cells were isolated from normal rat liver and kept in culture. Rat fibroblasts, monocytes and peritoneal macrophages were also studied. Immediately after isolation the steady state level of syndecan messages in hepatocytes was comparable to that of the normal liver. The expression increased at day one and then remained constant until day five. Ito and endothelial cells contained a low amount of syndecan message. Freshly isolated Kupffer cells failed to express syndecan, but strong upregulation was found on the first day in culture which gradually decreased by day 5. Syndecan transcripts were dose and time dependently upregulated by endotoxin and gamma interferon in Kupffer cells. Endotoxin had no effect on fibroblasts. PMID- 7980566 TI - Involvement of NF-kappa B activation in thrombin-induced human vascular smooth muscle cell proliferation. AB - A thrombin receptor has been cloned and is thought to mediate a variety of thrombin-induced responses. However, the transcription factors important for postreceptor signaling have been little clarified. The post-receptor signals are mediated by several protein kinases responsible for NF-kappa B activation, and most thrombin-inducible genes have the kappa B sequence in the regulatory elements. The possibility that NF-kappa B may participate in thrombin signaling was therefore investigated in cultured human vascular smooth muscle cells (VSMCs). Thrombin receptor stimulation resulted in activation of NF-kappa B. Furthermore, treatment of cells with antisense p65 ODNs of NF-kappa B inhibited thrombin-stimulated growth of VSMC in vitro. Results indicate that the activation of NF-kappa B is involved in thrombin signaling and that this pathway causes the proliferation of VSMC induced by thrombin. Therapeutic potential of antisense NF kappa B ODNs for the treatment with atherosclerosis and restenosis is also indicated. PMID- 7980567 TI - Effect of carboxyterminal modification on the oligomeric structure of human beta hemoglobin. AB - A broad beta chain band region containing multiple components was observed with both native beta and Des(His-146, Tyr-145) beta chains following isoelectric focusing on agarose gels (pH 6.0-8.0). In contrast to the tetramer-monomer system of beta chains, a distinct separation of three components (tetramer, dimer and monomer) was seen for Des(His-146, Tyr-145) beta chains indicative of an oligomeric structural beta model with a stable dimer species. Protein dilution (500 to 15.6 microM in heme) amplified the more cathodic (presumably dimeric and monomeric) components of these chains, and titration with partner alpha chains resulted in a selective depletion of the monomer (most cathodic) component which could be quantitatively correlated with assembly of the hemoglobin tetramer. PMID- 7980568 TI - Expression of transforming growth factor-beta 1-4 in the chick limb bud mesenchymal cells: regulation by 1,25-dihydroxyvitamin D3. AB - When mesenchymal cells from the early chick limb bud (stage 23-24) are plated at high cell density they spontaneously undergo chondrogenesis, implicating extensive cell-to-cell interactions. In the past it has been shown that TGF-beta or 1,25 dihydroxyvitamin D3 influences this process. In the present study we investigated the expression of TGF-beta isoforms in the mesenchymal cells after treatment with 1,25-dihydroxyvitamin D3. We found that TGF-beta 2 was down regulated due to the treatment. The size of the transcripts was the expected as described for sternum cartilage cells but with differential use preference. PMID- 7980569 TI - Protection by prosaposin against ischemia-induced learning disability and neuronal loss. AB - Prosaposin, the protein precursor of saposins A, B, C, and D which activate sphingolipid hydrolases, is abundant in several brain regions including the hippocampus. We infused prosaposin continuously for 7 days into the lateral ventricle of gerbils starting 3 hours before 3-min of forebrain ischemia. Using the step-down passive avoidance task, we demonstrated that ischemia-induced learning disability is prevented almost completely by prosaposin infusion. Subsequent light and electron microscopic examinations showed that pyramidal neurons in the CA1 field of the hippocampus as well as synapses within the strata moleculare, lacunosum/radiatum and oriens of the field were significantly more numerous in gerbils infused with prosaposin infusion than in those receiving saline infusion. These findings suggest that prosaposin possesses neurotrotrophic activity to protect hippocampal CA1 neurons from lethal ischemic damage. PMID- 7980570 TI - Baculovirus-mediated high level expression of a mammalian DNA methyltransferase. AB - The murine C-5 cytosine DNA methyltransferase (MTase, E.C.2.1.1.37) containing a hexahistidine affinity leader peptide has been expressed at levels which are at least 50-fold higher than previously reported. The recombinant enzyme has activity levels similar to the wild-type enzyme. The recombinant polypeptide binds to and elutes from a nickel affinity resin (IMAC resin). No dramatic differences in post-translational modification between the wild-type and recombinant enzyme were observed. The recombinant system will be useful in performing site-directed mutagenesis and will facilitate enzymological and biological investigations of this enzyme. PMID- 7980571 TI - RU486 and calcium fluxes in human spermatozoa. AB - RU486 decreases the intracellular free calcium concentration in human spermatozoa incubated in capacitation medium. We investigated the calcium fluxes that this progesterone antagonist acts on. We found that 10(-5) M RU486 slowed down the basal calcium influx while progesterone accelerated it. Moreover, in the same way as RU486 inhibits the calcium increase promoted by progesterone, it inhibited the calcium influx stimulated by 10(-6) M thapsigargin, an endoplasmic reticulum Ca(2+)-ATPase inhibitor. So we speculated that RU486 does not necessarily compete for the same binding sites as progesterone to exert its inhibitory action. In the absence of extracellular calcium, pretreatment by 10(-5) M RU486 decreased the peak of [Ca2+]i released by 5 microM ionomycin. This indicates that RU486 could also act at the membrane level of some intracellular organelles of calcium storage. PMID- 7980572 TI - The tetratricopeptide repeat-domain of the PAS10 protein of Saccharomyces cerevisiae is essential for binding the peroxisomal targeting signal-SKL. AB - The PAS10 gene was found in a two-hybrid screen for the isolation of genes encoding proteins which interact with the C-terminal peroxisomal targeting signal -SKL. The PAS10 protein is known to be involved in import of proteins into peroxisomes and to contain a tetratricopeptide repeat (TPR) domain. All TPR containing proteins involved in diverse processes like mitosis or RNA-synthesis share the ability to interact with other proteins. Here we show that the PAS10 protein interacts in vivo with the C-terminal peroxisomal targeting signal. The part essential for this interaction contains the complete tetratricopeptide repeat domain. PMID- 7980573 TI - Expression of human alpha 1-antitrypsin in mouse after in vivo gene transfer to hepatocytes by small liposomes. AB - A plasmid (pTG7101) containing the full-length human alpha 1-antitrypsin gene was encapsulated in small liposomes and used for "in vivo" gene transfer to mouse hepatocytes, by i.v. injection (100 ng DNA/mouse and dose). The expression of human protein was evaluated by microspectrophotometry after human alpha 1 antitrypsin immunoperoxidase reaction on liver cryosections and the presence in mouse plasma of de novo synthesized protein was detected by ELISA analysis. Our results indicate that a single dose of encapsulated plasmid induces the expression of human alpha 1-antitrypsin in mouse hepatocytes and a large effect (70%) remains two weeks after treatment. However, no effect was observed when mice were treated with buffer or free plasmid (100 ng/mouse) plus an equivalent lipid dose of empty liposomes. In addition, whereas no additive effect was observed after repetitive treatment-doses, the partial hepatectomy three hours after a single treatment-dose, significantly increased the presence of human alpha 1-antitrypsin in mice plasma. PMID- 7980574 TI - Influence of MA internal sequences, but not of the myristylated N-terminus sequence, on the budding site of HIV-1 Gag protein. AB - HIV-1 Gag protein intracellular transport and budding was investigated by altering the sequence of the MA domain, which directly bears an essential N terminal myristyl adduct and forms the viral matrix after Gag proteolysis in mature virions. We found that removal of a substantial MA internal segment did not abolish the assembly and budding of Gag particles, but rather diverted these events to intracellular cisternae. The internally deleted Gag was further modified by substituting either of two heterologous myristylated N-termini for the natural one: amino acids 1-12 from v-Src oncoprotein (for which a membrane bound intracellular receptor has been postulated), or amino acids 1-12 from Poliovirus polyprotein (for which no membrane-targeting function has been demonstrated). Both Src-Gag and Polio-Gag chimerae exhibited transport and processing characteristics similar to those of the MA-deleted Gag. These results are discussed with respect to the possible transport pathway of HIV-1 Gag. PMID- 7980575 TI - The genomic organization and functional analysis of the promoter for the human angiotensin II type 1 receptor. AB - We have cloned and characterized several human angiotensin II type 1 receptor (hAT1R) cDNAs by utilizing the 5'-RACE procedure. Sequence analysis demonstrated that human AT1 receptors are encoded by at least four distinct mRNA transcripts sharing an identical open reading frame, but differing in their organization of 5'-untranslated sequences. Therefore, even though multiple alternatively spliced forms of hAT1R mRNA are transcribed, they are all translated into identical receptors since the entire open reading frame of this receptor is harbored on a single exon. None of these exons coding for 5'-untranslated sequence is expressed in a tissue specific manner. By comparing the 5'-RACE cDNA clones with our hAT1R genomic clones, the organization of the hAT1R gene was determined. The human AT1 gene is comprised of at least four exons and spans at least 60 kb. Several putative promoter regions were characterized by utilizing primer extension and luciferase reporter gene constructs transfected into human adrenal cells. These results indicate that we have cloned a functional promoter for the hAT1R gene. Furthermore, this promoter harbors an adrenal specific response element. PMID- 7980577 TI - Direct proof of nitric oxide formation from a nitrovasodilator metabolised by erythrocytes. AB - When 15N-isosorbide dinitrate was injected into rats, the venous blood showed a 2 line hyperfine structure in the electron spin resonance (ESR) spectra of NO hemoglobin (HbNO), proving generation of 15N-NO. When human blood was mixed with 15N-isosorbide dinitrate anaerobically, ESR spectra showed initially 14N-HbNO, which was then overwhelmed with the increased 15N-HbNO. With deoxygenation of the blood of another 4 male donors without addition of isosorbide dinitrate, two showed 14N-HbNO, but others did not, suggesting varied amount of NO-precursers, nitrosothiols, in human blood. Neither N-ethylmaleimide nor S-hexylglutathione, a glutathione-S-transferase inhibitor, inhibited the formation of UbNO in the hemolysate mixed anaerobically with isosorbide dinitrite. PMID- 7980576 TI - Very low density and low density lipoproteins induce nitric oxide synthesis in macrophages. AB - The effect of lipoproteins on rat peritoneal macrophage nitric oxide (NO) production was studied. Very low density (VLDL) and low density (LDL) but not high density lipoprotein (HDL) stimulated NO production at 12, 24 and 48 hr of incubation with macrophages. Forty-eight hour incubation of macrophages with VLDL or LDL increased NO production from 10.8 nmoles/10(6) cells in control to 249 and 60 nmoles/10(6) cells, respectively. VLDL-induced nitric oxide production was 825 nmoles/10(6) after 12 days of incubation. VLDL by itself or in the presence of LDL and HDL induced similar levels of NO in 24 hrs. Lipoproteins were without effect on NO, when incubated with macrophages in the absence of L-arginine and in the presence of nitric oxide synthase inhibitor monomethyl-L-arginine (L-NMMA). Oxidized VLDL was as effective as native form in the induction of macrophage NO, whereas oxidized LDL did not induce NO production. Further, the presence of 100 microM vitamin E in the incubation had no effect on VLDL- and LDL-induced NO production. Preincubation of macrophages with VLDL and LDL for 3hr or 6hrs activated macrophages to generate NO. These effects of lipoproteins could be of interest in the pathophysiology of lipoproteins and NO mediated diseases. PMID- 7980578 TI - Regulation of transforming growth factor-beta 1 (TGF-beta 1) expression with a novel TGF-beta 1 complementary DNA. AB - We describe here a novel TGF-beta 1 complementary DNA (antisense oligomer) that is specific for TGF-beta 1 genomic DNA. The TGF-beta 1 antisense oligomer, complementary to the nucleotides flanking the first transcription start site of the human TGF-beta 1 gene and phosphorothioate modified, was efficacious in: a) constraining TGF-beta 1 promoter activity; b) reducing TGF-beta 1 secretion; and c) preventing TGF-beta 1 dependent inhibition of DNA synthesis in TGF-beta sensitive A-549 human adenocarcinoma cells. The biologic activities of the TGF beta 1 antisense oligomer were sequence specific since neither the TGF-beta 1 sense oligomer nor the TGF-beta 1 missense oligomer prevented TGF-beta 1 expression. Our findings, in addition to demonstrating the efficacy and specificity of the TGF-beta 1 antisense oligomer, suggest that the oligomer might be of value for the treatment of diseases in which TGF-beta 1 overexpression might play a pathogenetic role (e.g., diabetic renal disease, AIDS). PMID- 7980579 TI - Suppression of cyclin D1 mRNA expression by the angiogenesis inhibitor TNP-470 (AGM-1470) in vascular endothelial cells. AB - The effects of TNP-470 on DNA synthesis and the expression of c-myc and cyclin D1 mRNAs were investigated in human umbilical vein endothelial (HUVE) cells synchronized by serum depletion and stimulated with bFGF and serum. DNA synthesis occurring 16 h after stimulation was inhibited when TNP-470 was present from 2 to 6 h after stimulation. C-myc mRNA expression occurring 2 h after stimulation was not inhibited by the addition of TNP-470. Cyclin D1 mRNA expression occurring 6 h after stimulation was suppressed in the presence of TNP-470 from 2 to 6 h after stimulation. On the other hand, cyclin D1 expression was not suppressed in the TNP-470-insensitive human tumor cell line WiDr. These results suggest that the inhibition of HUVE cells by TNP-470 is due to the suppression of cyclin D1 expression in mid G1 phase. PMID- 7980580 TI - Isolation and characterization of human Nramp cDNA. AB - The mouse gene locus Lsh/Ity/Bcg regulates macrophage activation for antimicrobial activity against intracellular pathogens. A candidate gene, designated natural resistance-associated macrophage protein gene (Nramp), recently isolated from a mouse pre-B cell cDNA library, encodes an integral membrane protein that has structural homology with known prokaryotic and eukaryotic transport systems. In the present study, the cDNA for human Nramp was isolated by screening a human monocyte cDNA library. The cDNA was 2245 bp in length and coded for a protein of 483 amino acid residues with a molecular weight mass of 52.8 kDa. The deduced amino acid sequence was 89% homologous with that of mouse. Southern blot analysis indicated a single gene for Nramp counterpart in the human genome. Northern blot analysis revealed a single species of mRNA of approximately 2.5 kb. PMID- 7980581 TI - Modulation of epidermal growth factor and keratinocyte growth factor effects on human keratinocyte growth by protein kinase C inhibitor, GF 109203X: comparison to fibroblast growth modulation. AB - In this study, epidermal growth factor (EGF), 20 ng/ml, and keratinocyte growth factor (KGF), 10 ng/ml, were able to stimulate human keratinocyte growth only in presence of GF 109203X 1 microM, a selective PKC inhibitor. This suggests that PKC negatively controls keratinocyte growth in response to EGF and KGF. On the other hand, EGF and KGF have no significant effect on PKC activity. In contrast, in human fibroblasts, EGF stimulated fibroblast growth in the presence or not of GF 109203X. Thus, EGF seems to stimulate fibroblast growth in a PKC independent manner. Moreover, EGF didn't modify significantly PKC activity in fibroblasts. KGF had no effect on fibroblasts. These results show differences in the interconnections between PKC and EGF transduction pathway in the modulation of human keratinocyte and fibroblast growth. Moreover, they especially demonstrate that PKC would negatively control human keratinocyte growth in response to EGF and also to KGF. PMID- 7980582 TI - Beta-structure in human amylin and two designer beta-peptides: CD and NMR spectroscopic comparisons suggest soluble beta-oligomers and the absence of significant populations of beta-strand dimers. AB - Intensity variation for the positive far UV CD band was observed for three 'beta sheet' peptides. In 6% HFIP, an amyloidogenic species (human pancreatic amylin) displays, on standing, an extremely intense 192-nm band which diminishes upon physical agitation. A concurrently formed Tyr sidechain band at 274 nm disappears completely with agitation, linking the enhancement of the 192-nm band to the highly ordered stacking of beta-sheets. NMR studies indicate that the beta-states of the three peptides are oligomeric, not beta dimers. A membrane-forming EAK peptide displays NMR peaks due to the low concentration of 'random coil' monomers present in slow equilibrium with beta-oligomers; solutions of a more hydrophobic ELKA peptide, which displays an intense 195-nm band, contain only oligomeric species. NMR studies at 25% HFIP revealed the structural requirements for inhibition of beta-oligomer formation. PMID- 7980583 TI - Vitamin D metabolites and extracellular calcium regulate calcium currents in hemocytes of land snails. AB - Intracellular exchangeable calcium and calcium efflux were investigated in cultured amoebocytes of land snails. Low extracellular calcium concentration (0.32 mM) initiated a rapid increase of outward calcium currents and decrease of intracellular exchangeable calcium. On the other hand, high extracellular calcium concentration (32 mM) increased intracellular exchangeable calcium. Actions of vitamin D metabolites were most prominent under non-physiological concentrations of extracellular calcium. Metabolite E activated a calcium pump while 25-hydroxy vitamin D3 deactivated the pump. Both metabolites increased calcium transfer into stored pools. PMID- 7980584 TI - Nonsense mutations in human transcobalamin II deficiency. AB - Reverse transcription-polymerase chain reaction has been used to amplify, clone and sequence transcobalamin II (TC II) cDNA from fibroblasts of three unrelated TC II deficient patients who had undetectable TC II protein and mRNA in their fibroblasts (Li et al., Biochem. J, 301, 585-590, 1994). One child of a consanguineous marriage contained a single nucleotide deletion at position 258 in both alleles, while the child from unrelated parents revealed a nonsense mutation at position 1206 in one allele and a single nucleotide deletion at position 483 in the other allele. Both the single nucleotide deletion mutations caused a frameshift and introduced a premature termination codon (indirect nonsense mutations). No mutation was detected in TC II cDNA from the third patient. Based on these results we suggest that TC II deficiency due to lack of TC II protein/mRNA in these patients is due to heterogeneous types of nonsense mutations. PMID- 7980585 TI - Efficient unwinding of triplex DNA by a DNA helicase. AB - Sequence specific triple helix formation shows promise as a strategy for gene specific inhibition of gene expression by blocking promoters or enhancers. Therefore, it is important to understand how this unusual structure affects DNA metabolic processes other than transcription. It has been shown that triplexes block in vitro DNA synthesis catalyzed by purified DNA polymerases. We report here that a purified DNA helicase unwinds a triple helical substrate with an efficiency similar to that observed with a comparable duplex species. These model studies suggest that triple helices will not seriously inhibit DNA replication or recombination in vivo, since DNA polymerases are preceded by helicases in the fully assembled replication holoenzyme. PMID- 7980586 TI - Isolation of rat TATA factor as an active 75kDa protein complex. AB - A general transcription factor TFIID was purified from rat liver by a sequential column chromatography including organomercurial Sepharose and Sephacryl S-200 chromatographies, which were developed with an acidic buffer (pH5.5). Analyses by SDS-polyacrylamide gel electrophoresis, assay of eluants after renaturation, and immunoblotting showed that isolated TATA factor is an active 75kDa protein complex which contains 36kDa TATA-binding protein. PMID- 7980587 TI - Purification and characterization of brain clusterin. AB - Clusterin, a 70-80 kDa sulfated glycoprotein found in numerous tissues, is also known as complement lysis inhibitor (CLI), apolipoprotein J, SP-40,40, TRPM-2, and SGP-2. In Alzheimer disease (AD), clusterin mRNA is increased, whereas clusterin protein is found in deposits of beta-amyloid (A beta). These studies characterized clusterin protein from human brain. In extracts from cortex and hippocampus, clusterin was about 40% higher in AD than in controls. Purified clusterin from human brain was slightly smaller than serum clusterin. Brain and serum clusterin were indistinguishable in the inhibition of complement-mediated hemolysis. Both serum and brain clusterin were indistinguishable in inhibiting the aggregation of A beta and promoting oxidative stress in rat pheochromocytoma PC12 cells (MTT assay). The inhibition of A beta aggregation and enhancement of A beta toxicity by clusterin suggest new mechanisms in AD. PMID- 7980588 TI - Binding and cAMP studies of melanotropin peptides with the cloned human peripheral melanocortin receptor, hMC1R. AB - Binding and stimulation of cAMP by the melanotropin peptides alpha-MSH (alpha melanocyte-stimulating hormone) and its superpotent analogues [Nle4, DPhe7]alpha MSH (MT-I) and Ac-[Nle4,[formula: see text]alpha-MSH4-10-NH2 (MT-II) were undertaken to examine their respective properties on the human peripheral melanocyte melanocortin receptor, hMC1R. alpha-MSH was found to possess a binding IC50 value of 6.5 +/- 0.9 x 10(-9) M and cAMP EC50 value of 2.0 +/- 0.6 x 10(-9) M. MT-I possesses a binding IC50 value of 1.2 +/- 0.3 x 10(-9) M and a cAMP EC50 of 0.5 +/- 0.03 x 10(-9) M. MT-II possesses a binding IC50 of 0.57 +/- 0.08 x 10( 9) M and cAMP EC50 value of 0.20 +/- 0.05 x 10(-9) M. PMID- 7980589 TI - Adenosine induces C1- efflux in endothelial cells via a pertussis toxin-sensitive G protein. AB - To examine the biological role of adenosine A1 receptors in bovine pulmonary artery endothelial cells, we measured intracellular Cl-concentration [Cl-]i, using 10mM 6-methoxy-N-(3-sulfopropyl) quinolinium monohydrate (SPQ). N6 cyclopentyladenosine (CPA), a selective A1 agonist, at 10(-8)M to 10(-5)M, rapidly decreased [Cl-]i by 30% to 51%, without a rapid elevation in [Ca2+]i and cyclic AMP. This reduction in [Cl-]i was completely inhibited by 10(-8)M FK453 (a selective A1 antagonist), 500ng/ml pertussis toxin (IAP), and 2.5mM N phenylanthranilic acid (NPA) (a Cl- channel blocker). We conclude that an A1 receptor in endothelial cells activates Cl- efflux via a PTX-sensitive G protein. PMID- 7980590 TI - Multiple effects on peripheral hematology following administration of recombinant human interleukin 12 to nonhuman primates. AB - Interleukin 12 has demonstrated a wide spectrum of bioactivity on T and NK cells both in vitro and in vivo. Therapeutic potential of these activities has been suggested by studies in murine tumor, viral and microbial models of disease. We have investigated the in vivo effect of rhlL-12 in cynomolgus monkeys treated with 1 micrograms/kg/day by bolus i.v. or s.c. injection for 5 days. Treated group transient decreases in total WBC counts as compared to controls, with reversable decreases seen mainly in the lymphocyte and monocyte subsets. Phenotypic analysis showed a decrease in the number of CD4+ and CD8+ cells/microL on Days 2 and 4. Reversible thrombocytopenia and anemia were noted in both treated groups as compared to controls. Plasma neopterin concentrations were increased in both treated groups as compared to controls. These data show that rhlL-12 has multiple effects on peripheral hematology and suggests that this model may be useful to investigate in vivo bioactivity of rhlL-12. PMID- 7980591 TI - Prolactin-induced phosphorylation and nuclear translocation of MAP kinase in Nb2 lymphoma cells. AB - The coupling of prolactin (PRL) receptor ligation to activation of mitogen activated protein (MAP) kinase was sought in rat Nb2 lymphoma cells, a pre-T lymphocyte line dependent upon lactogens for proliferation. Addition of PRL (20 ng/ml) to Nb2 cells, growth arrested in the early G1 phase of cell cycle, stimulated rapid tyrosyl phosphorylation of MAP kinase (min). Phosphorylated MAP kinase subsequently translocated to the nucleus, with kinetics essentially identical to those demonstrated for nuclear accumulation of PRL. The rapidity of MAP kinase activation suggests an intermediary role for this enzyme in PRL receptor signalling. Moreover, nuclear translocation of MAP kinase provides an interactive mechanism by which PRL, together with its nuclear receptor, may regulate transcription requisite for mitogenesis. PMID- 7980592 TI - Cells overexpressing Hsp27 show accelerated recovery from heat-induced nuclear protein aggregation. AB - Protein denaturation/aggregation upon cell exposure to heat shock is a likely cause of cell death. In the nucleus, protein aggregation has often been correlated to inhibition of nuclear located processes and heat-induced cell killing. In Chinese hamster O23 cells made thermotolerant by a prior heating (20'44 degrees C + 10h 37 degrees C) which induces the whole spectrum of heat shock proteins (hsps), the extent of nuclear protein aggregation during heat shock is reduced and the rate of recovery from aggregation after heat shock is enhanced. In contrast, a heat resistant Chinese hamster cell line overexpressing only hsp27 shows an unaltered sensitivity to formation of nuclear protein aggregates by heat, but shows the same enhanced rate of recovery from nuclear protein aggregation as thermotolerant cells. This suggests that accelerated recovery of protein aggregation could be partly responsible for hsp27-mediated thermoprotection. PMID- 7980593 TI - A P-loop related motif (GxxGxxK) highly conserved in sulfotransferases is required for binding the activated sulfate donor. AB - A nucleotide binding motif termed the P-loop has been described for ATP- and GTP binding proteins. The primary structure typically consists of a glycine-rich region followed by a conserved lysine. A related structure (GxxGxxK) noted in sulfotransferases has been suggested to be important for the binding of the cofactor 3'-phosphoadenosine-5'-phosphosulfate (PAPS), the universal sulfate donor for this class of enzymes. Using molecular techniques, point mutations that substituted alanines for the putative critical residues were introduced into the cDNA for estrogen sulfotransferase. The altered construct, although fully expressed by Chinese hamster ovary-K1 cells, demonstrated negligible enzymatic activity and failed to photoaffinity label with [35S]PAPS. In contrast, a construct in which three other amino acids in the region of the P-loop motif were similarly mutated retained activity and was photoaffinity labeled with [35S]PAPS. These data strongly support the notion that the P-loop motif found in all cloned sulfotransferases constitutes, at least in part, the PAPS binding site for these enzymes. PMID- 7980594 TI - Interleukin-1 beta (IL-1 beta) induces transforming growth factor-beta, (TGF-beta 1) production by rat aortic smooth muscle cells. AB - In cultured rat aortic smooth muscle cells (RASMCs) IL-1 beta induced TGF-beta 1 mRNA expression, which was concentration (10 pM-10 nM)- and time (2-48 h) dependent, and sensitive to cycloheximide. The maximal increase in TGF beta 1 mRNA was 4.5 times the basal level at 10 nM of IL-1 beta. A parallel increase in TGF-beta 1 protein in the culture medium of IL-1 beta-stimulated RASMCs was also observed. A detectable level of TGF-beta 1 was found 8 h after stimulation and a plateau was reached at 72 h with a maximal increase of 5-fold and was inhibited by IL-1 receptor antagonist (IL-1ra). Our data demonstrate for the first time that IL-1 beta is a potent inducer of TGF-beta 1 synthesis and release in vascular smooth muscle cells. PMID- 7980595 TI - Ubiquitin changes in human biceps muscle following exercise-induced damage. AB - Changes in ubiquitin levels were characterized in human biceps muscle following high-force eccentric exercise. Volunteers performed damaging eccentric-isokinetic actions of the biceps muscle with the non-dominant arm. Protein extracts of biopsy tissue samples taken two days post-exercise were run on SDS polyacrylamide gels, analyzed densitometrically and revealed a 64% higher level of a protein band at 12 kD. New monoclonal immunoblotting techniques identified the band as free ubiquitin. On these blots, free ubiquitin increased in the exercised sample by 55% over the control, and ubiquitin conjugates of varying molecular weights follow a similar pattern. The changes seen in both free and conjugated ubiquitin suggest that their increases are involved in the response to exercise-induced muscle damage. PMID- 7980596 TI - Association of structural polymorphism of the dopamine D2 receptor gene and alcoholism. AB - To examine the possible association between three recently identified structural polymorphisms of the dopamine D2 receptor (DRD2) gene and alcoholism, we compared allele frequencies of these polymorphisms in 280 Japanese alcoholics and 289 normal controls. The results revealed that only one of three variants identified in white individuals existed in the alcoholic and control Japanese. The frequency of the Cys311 variant allele was significantly higher in alcoholics (.063) than in controls (.029). All of the subjects with the variant allele were heterozygous Ser311/Cys311. Patients with Cys311 allele had less severe symptoms of alcoholism than did those with homozygous Ser311, especially symptoms related to loss of control over drinking. The coprevalence of other psychiatric disorders including schizophrenia did not differ between the two patient groups. These results suggest that the D2/Cys311 variant is associated with some type of alcoholism in Japanese. PMID- 7980597 TI - Transforming growth factor-beta 1 post-transcriptionally inhibits mouse growth hormone releasing factor secretion in placenta. AB - The aim of this study was to investigate whether TGF-beta 1 regulates mouse GHRF secretion by primary cultures of placental cells from day 12 of pregnancy. Ten ng/ml TGF-beta 1 significantly inhibited mouse GHRF secretion by the third day of culture. The lowest concentration of TGF-beta 1 that significantly inhibited mouse GHRF secretion was 1 ng/ml. The inhibitory effect of TGF-beta 1 on mouse GHRF secretion was completely eliminated by addition of an anti-TGF-beta 1 antibody. Steady-state levels of mouse GHRF mRNA as assessed by Northern analysis was not reduced by incubation of placental cells from day 12 of pregnancy with 10 ng/ml TGF-beta 1 for 5 days. Both placenta and decidua expressed TGF-beta 1 mRNA, and the level of TGF-beta 1 mRNA in decidua increased during gestation while the level of TGF-beta 1 mRNA was constant throughout gestation. These findings suggest that TGF-beta 1 is one of the potent regulators of mouse GHRF secretion and that TGF-beta 1 regulates mouse GHRF secretion in an autocrine or paracrine manner in the mouse placenta in vivo. PMID- 7980598 TI - The two subunits of a phospholipase A2 inhibitor from the plasma of Thailand cobra having structural similarity to urokinase-type plasminogen activator receptor and LY-6 related proteins. AB - Amino acid sequences of the two subunits (31-kDa and 25-kDa subunits) of a phospholipase A2 (PLA2) inhibitory protein, purified from the blood plasma of Thailand cobra Naja naja kaouthia, were determined by alignment of peptides obtained by lysyl endopeptidase, staphylococcal V8 protease and endoproteinase Asp-N digestions. The respective subunits were composed of 188 and 185 amino acid residues, and the former contained one asparagine-linked sugar chain at the position 157. There was 29% identity between 31-kDa and 25-kDa subunits. The analysis of internal homology in each sequence of the two subunits revealed the existence of two repeats of approximately 90 amino acid residues. These sequence units were found to be significantly homologous to those of urokinase-type plasminogen activator receptor and of Ly-6 related proteins, such as Ly-6A/E, Ly 6C, ThB, and CD59 antigens. PMID- 7980599 TI - Demonstration of derivation of rat urinary bradykinin from plasma low-molecular weight kininogen: a study using kininogen-deficient rats. AB - The origin of urinary bradykinin was defined by use of plasma kininogen-deficient B/N-Katholiek rats, whose ureter urine contains very low amount of urinary kinin. The kinin level increased after the rats received an infusion of normal plasma. Furthermore, the bradykinin content in the ureter urine of these kininogen deficient rats increased more by infusion of partially purified rat- low molecular-weight kininogen than by that of high-molecular-weight kininogen. Urinary kallikrein activity of B/N-Katholiek rats was enzymatically identical with that of normal B/N-Kitasato rats. These results indicate that urinary bradykinin found in the ureter urine of normal rats is derived from plasma low molecular-weight kininogen by cleavage by urinary kallikrein. PMID- 7980600 TI - Characteristics of carcinoembryonic antigen (CEA) expressed in different cell types: evidence that CEA can function as an adhesion molecule and as a repulsion molecule. AB - The characteristics of carcinoembryonic antigen (CEA) molecules expressed by different cell types have been examined using cDNA transfection into cells of epithelial, neuroectodermal and hematopoietic origin. Variability in the CEA molecules was observed in terms of monoclonal antibody binding, apparent molecular weight and sialic acid content, although this was not cell type specific. CEA was found to mediate homotypic as well as heterotypic intercellular adhesion independently of the cell type and despite differences in the sialic acid content. Although CEA was shown to function as a homophilic cell adhesion molecule in most cells, expression of CEA in one cell line led to a reduction in both homotypic and heterotypic cell adhesion, suggesting that it can under certain circumstances also function as a repulsion molecule. PMID- 7980601 TI - Plasmalogen phospholipids as potential protectors against lipid peroxidation of low density lipoproteins. AB - A phospholipid subgroup with potential antioxidant properties, the plasmalogen (1 alkenyl, 2-acyl-) fraction, was determined to constitute about 4.5% of total LDL phospholipids. In vitro oxidation of LDL by 2,2'-azobis-(2-amidinopropane hydrochloride) (AAPH, 0.5-10mM) or 5 microM copper induced a selective reduction of plasmalogen subgroups in phosphatidylcholine and phosphatidylethanolamine by 15%-35% within 30 min. Under the same experimental conditions alpha tocopherol (vitamin E) levels were lowered by 5%-40%, indicating a comparable sensitivity of plasmalogen phospholipids and alpha tocopherol towards oxidative attack by AAPH and copper. In vitro enrichment of LDL with 1-alkenyl, 2-lyso-phosphatidylcholine increased the lag phase of formation of conjugated double bonds induced by oxidation of the particles with copper. Incorporation of the lyso plasmalogen did not affect the maximal contents of conjugated dienes in copper oxidized LDL. Due to their relatively high concentration in LDL, their pronounced sensitivity towards oxidation and their capacity to increase the oxidative resistance of the particles, plasmalogen phospholipids may play a significant role in the defense of LDL particles against oxidative stress. PMID- 7980602 TI - Dopachrome tautomerase is a zinc-containing enzyme. AB - Dopachrome tautomerase (DCT) catalyzes the conversion of L-dopachrome into 5,6 dihydroxyindole-2-carboxylic acid through the melanogenic biosynthetic pathway. This enzyme, also named TRP2, belongs to the family of the tyrosinase related proteins. The three members of the family contain two highly conserved metal binding sites with three histidines on each. Tyrosinase has copper at its active site. It was assumed that although DCT might have copper in those metal binding sites, its active site could be related to other two putative iron-binding sites located in different positions. Based on apoDCT preparation with cyanide and reconstitution experiments, we propose that DCT have zinc instead of copper at the two metal-binding sites and that those sites actually correspond to the active site. The involvement of zinc, which cannot undergo redox reactions, accounts for the reaction that DCT catalyzes, a tautomerization versus the copper mediated oxidations catalyzed by tyrosinase. PMID- 7980603 TI - Cloning, characterization and chromosomal assignment of the human genes homologous to yeast PMS1, a member of mismatch repair genes. AB - Mutations in genes associated with the DNA mismatch repair system were considered to play important roles in predisposition to cancer, since hMSH2 and hMLH1, human homologues of yeast MSH2 and MLH1 as well as bacterial mutS and mutL genes, were found to be involved in hereditary nonpolyposis colorectal cancer (HNPCC). In addition, yeast PMS1 that is homologous to bacterial mutL and hexB, has also been proven to be related to the DNA mismatch repair system. As the first step to understand whether human homologue of the yeast PMS1 gene is associated with genetic predisposition to cancer, we have isolated and analyzed human counterpart of yeast PMS1 genes. DNA sequencing analyses indicated that human PMS genes constituted a multiple gene family and that some of the family members have been mapped to chromosomal bands 7q11.23 and 7q22 by fluorescent in situ hybridization. PMID- 7980604 TI - Chloride channel blockers inhibit the Na+/I- symporter in thyroid follicles in culture. AB - Porcine thyroid cells in culture are able to reorganize into well-polarized follicle-like structures in the presence of cAMP analogs. These follicles exhibit on their basolateral membrane domain the Na+/I- symporter which allows iodide to accumulate in the thyrocytes. The initial rate of iodide influx through the Na+/I symporter is inhibited up to 98% by the chloride channel blockers. 5 nitro-2(3 phenylpropylamino)benzoic acid and 3',5-Dichlorodiphenylamine-2-carboxylic acid are the most effective inhibitors, with a K0.5 value of 60 microM. This inhibition is not secondary to inhibition of chloride transport. Other chloride transporter blockers have been studied but showed lesser activities. PMID- 7980605 TI - Modulations of 92kDa gelatinase B and its inhibitors are associated with HIV-1 infection in human macrophage cultures. AB - The macrophage-secreted 92-kDa type IV collagenase and metalloproteinases play a critical role in cell microenvironment regulation and cell movement. HIV infection of macrophages might be capable of deregulating the expression of these gelatinases. Hence, human monocyte-derived-macrophages were infected by lymphotropic HIV-1/Lai and monocytropic HIV-1/DAS isolates. Gelatinase activity and gelatinase and inhibitor (TIMP, alpha 2M) biosyntheses were evaluated in supernatants and cellular extracts. Our data suggest that HIV infection facilitates gelatinase secretion and intracellular inhibitor retention. These argue for the increase of free proteinase that could degrade barriers, which would permit cell movement and viral dissemination into tissues. PMID- 7980606 TI - Mechanistic implications of cyclic ADP-ribose hydrolysis and methanolysis catalyzed by calf spleen NAD+glycohydrolase. AB - Calf spleen NAD+glycohydrolase, besides its well known reactions, was shown to catalyze hydrolysis and methanolysis (with retention of configuration) of cyclic ADP-ribose, indicating that this classical NADase also belongs to the class of cyclic ADP-ribose hydrolases. No formation of cyclic ADP-ribose could be detected during the hydrolysis of beta-NAD+; moreover, the kinetic parameters of cyclic ADP-ribose seem to rule out that it is a kinetically competent reaction intermediate in the conversion of NAD+ into ADP-ribose by this enzyme. PMID- 7980607 TI - Internalization of the type I angiotensin II receptor (AT1) is required for protein kinase C activation but not for inositol trisphosphate release in the angiotensin II stimulated rat adrenal zona glomerulosa cell. AB - A specific antibody, 6313/G2, to the N-terminus of the angiotensin II type I (AT1) receptor causes retention of the AT1 receptor in the plasma membrane of rat adrenal zona glomerulosa cells and stimulates steroidogenesis and inositol trisphosphate (IP3) release. Its effects are not significantly additive with those of angiotensin. In contrast, 6313/G2 completely inhibits angiotensin induced translocation of protein kinase C to the membrane fraction, although alone it has no effect. The data suggest that IP3 linked events, such as steroidogenesis, do not require receptor internalization, but protein kinase C activation does. They also confirm that protein kinase C activation is not required for stimulation of steroidogenesis in rat dispersed glomerulosa cells. PMID- 7980608 TI - Contrary results on mouse hepatitis virus type 3 susceptibility in A/J mouse hepatocytes of phosphatidylserine treatment and of a hypercholesterolaemic diet: no correlation with membrane fluidity levels. AB - The aim of this study was to examine whether or not membrane fluidity directly influences infection by enveloped viruses, and, more precisely here, the susceptibility of A/J mouse hepatocytes to Mouse Hepatitis Virus type 3 (MHV3). We therefore studied, in parallel, the effects on hepatocyte membrane fluidity and on intracellular viral titre of two treatments, i) a hypercholesterolaemic diet to increase the hepatocyte membrane cholesterol content, ii) direct phosphatidylserine incorporation into hepatocyte membrane. Membrane fluidity was monitored on isolated hepatocytes by fluorescence anisotropy with TMA-DPH, and the viral titre was determined by plaque assay. The results clearly demonstrate that membrane fluidity is not directly involved in viral infection mechanisms. PMID- 7980609 TI - Nitric oxide production by cells isolated from regenerating rat liver. AB - Nitric oxide (NO) production by cells of the regenerating liver was estimated from the amount of nitrite accumulated during 24 h in the culture media of hepatocytes, Kupffer cells and sinusoidal endothelial cells isolated at different times after partial hepatectomy (PHE). The time course of NO production was compared with the course of the proliferating activity of the same cells. During the time when liver cells pass through their first cell cycles, hepatocytes were the main producers of NO in the liver. The time-dependent changes of their NO production corresponded to those obtained with the whole liver and were inversely correlated with the DNA-synthesizing activity. The NO production by Kupffer and endothelial cells followed that by hepatocytes in this order; the time displacement between them corresponded to the schedule of their proliferating activity. The NO synthesis in non-parenchymal cells fluctuated in a similar way as in parenchymal cells and was minimal when DNA synthesis was manifest. PMID- 7980610 TI - Association of restriction fragment length polymorphism at the atrial natriuretic peptide gene locus with aldosterone responsiveness to angiotensin in aldosterone producing adenoma. AB - Primary aldosteronism is an important, potentially curable, form of hypertension. We examined the possible association between restriction fragment length polymorphisms in the atrial natriuretic peptide (ANP) gene and responsiveness of aldosterone to angiotensin II in 59 patients with primary aldosteronism due to aldosterone-producing adenoma (APA). Significant differences in the allelic frequencies of the BglI, TaqI and XhoI polymorphic sites at the ANP gene locus (chromosome 1; 1p36) between angiotensin II-unresponsive and angiotensin II responsive tumors were observed. Variation in the ANP gene between the two groups may result in altered expression of ANP within the adrenal gland, and may contribute to the biochemical regulation of aldosterone production of these two subgroups of patients with APA. PMID- 7980611 TI - Endothelin-1 activates mitogen-activated protein kinases through two independent signalling pathways in rat astrocytes. AB - Northern blot analysis and displacement study revealed that the endothelin (ET) receptor functionally expressed in rat primary cultured astrocytes is the ETB receptor. Mitogen-activated protein kinases (MAP kinases) in the cells were activated by 10 nM ET-1, a dose that maximally stimulated phosphoinositide hydrolysis. This activation was potently inhibited by pretreatment of the cells with phorbol 12-myristate 13-acetate (PMA) which leads to protein kinase C (PKC) down-regulation and was slightly inhibited by pretreatment with pertussis toxin (PTX). Pretreatment of the cells with PMA plus PTX completely inhibited the ET-1 augmented MAP kinase activity. Activation of MAP kinases was also induced by 0.1 nM ET-1, which hardly stimulated phosphoinositide hydrolysis. This activation was fully inhibited by pretreatment with PTX but insensitive to pretreatment with PMA. ET-1-stimulated production of inositol phosphates was not affected by pretreatment with PTX. These results suggest that activation of MAP kinases secondary to stimulation of the ETB receptor with ET-1 in rat primary cultured astrocytes was mediated through two independent signalling pathways. PKC dependent pathway and PTX-sensitive G protein-mediated pathway. PMID- 7980612 TI - Human cardiac fibroblasts express an angiotensin receptor with unusual binding characteristics which is coupled to cellular proliferation. AB - To assess the cellular localization of angiotensin receptors in human heart, we isolated human cardiac fibroblasts from explanted end-stage failing human hearts. As judged by an immunofluorescence assay, the isolated cells consisted of 96% of fibroblasts. Using receptor binding studies, we could identify a single angiotensin binding site on these cells, with a Kd of 0.6nM and a Bmax of 1.5 fmol/mg protein. Inhibiting concentrations 50 for Ang II and Ang I/II (1-7) were 40nM and 10nM, respectively. Stimulation with Ang II (100 nM) and Ang I/II (1-7) (100nM) led to cellular proliferation which could not be inhibited by Losartan or PD 123319. These results suggest that human cardiac fibroblasts express an as yet unknown angiotensin receptor-subtype. PMID- 7980613 TI - Apolipoprotein synthesis in human fetal intestine: regulation by epidermal growth factor. AB - In this investigation, human fetal intestine (17-20 wk) was used to study the synthesis of apolipoproteins (apo) A-I and B and its modulation by epidermal growth factor. Cultured jejunal explants were incubated with [3%S]-methionine, homogenized, immunoprecipitated and subjected to gel analysis. Radioactivity was detected mostly in apo A-I and, to a lesser extent, in both apo B-48 and apo B 100. However, apo B-48 was always the predominant form. The addition of EGF (100 ng/ml) resulted in a simultaneous decrease in apo B-100 synthesis and increase in apo B-48 production without a marked effect on apo A-I. Moreover, the incubation of jejunal explants with [14C] oleic acid documented the ability of fetal intestine to produce chylomicrons, VLDL, LDL and HDL. Therefore, the human fetal intestine has an efficient lipoprotein-lipid transport system and EGF is able to modulate levels of both apo B species as well as lipoprotein fractions. PMID- 7980614 TI - Recombinant polypeptides transplanted from pUMA vector-derived cRNAs are translocated through microsomal membranes and exported out of frog oocytes. AB - pSP64 derivatives were constructed to obtain cloning vectors suitable for in vitro transcription and subsequent in vitro synthesis of recombinant proteins equipped with N-terminal signal sequences. The amino acid sequence of the signal peptide was adapted and slightly modified from the one occurring in the neural cell adhesion molecule, NCAM. Its ability to direct recombinant proteins into secretory pathways was tested by in vitro translation in microsomal membrane containing reticulocyte lysates and by injection of the pUMA-derived cRNAs into Xenopus laevis oocytes. PMID- 7980615 TI - Structure of the rat thyroid transcription factor-1 (TTF-1) gene. AB - TTF-1 is a homeodomain-containing thyroid transcription factor which activates the genes of thyroid specific protein, thyroglobulin, thyroid peroxidase and thyrotropin receptor. We have cloned the TTF-1 gene from rat liver genomic library, and the exon/intron organization and the structure of the 5' flanking region were determined. The clone contained the 5.2 kbp upstream sequence from translation initiation site, and we found that the gene has a single intron in the coding sequence. We found in the 5' flanking region the TTF-1 binding consensus sequence, CTCAAGC, at -175 to -169, which overlaps the consensus sequence of CAAT box, DNase I foot print analysis has revealed that the region is protected by nuclear extract from thyroid cells but not by the extract from the liver, suggesting that expression of the TTF-1 gene is autoregulated by TTF-1. PMID- 7980616 TI - Production of Alzheimer 4kDa beta-amyloid peptide requires the C-terminal cytosolic domain of the amyloid precursor protein. AB - Amyloid precursor protein (APP) is metabolized through at least three pathways: the constitutive secretory pathway, the endosomal-lysosomal pathway and the 4-kDa A beta-producing pathway. The 4-kDa A beta (4 kDa A beta)-producing pathway which may play a primary role in the pathogenesis of Alzheimer's disease (AD) is presently unknown. In the present paper, we examine the production of the 4 kDa A beta in K562 lymphoid cells transfected with a truncated APP695 construct (APP delta 652-695) encoding an APP which lacks the cytosolic C-terminal domain except the four N-terminal amino acids, KKKQ. The APP delta 652-695-transfected cells (APP delta 652-695 cells) do not secrete 4 kDa A beta compared to APP 695 transfected cells (APP695 cells). Moreover, while the APP delta 652-695 and APP695 cells secrete equivalent levels of sAPP, the APP delta 652-695 cells accumulate less APP intracellularly than the APP695 cells. These results reveal that in the K562 cells (1), the last 43 amino acid residues at the C-terminus of APP are important in targeting APP through the 4 kDa A beta producing pathway and (2) processing of APP into 4 kDa A beta is independent of the known secretase pathway. PMID- 7980617 TI - "Identification of novel cDNAs encoding human kexin-like protease, PACE4 isoforms.". PMID- 7980618 TI - Search for endogenous ligands of the cannabinoid receptor. PMID- 7980619 TI - Radiation inactivation analysis of microsomal UDP-glucuronosyltransferases catalysing mono- and diglucuronide formation of 3,6-dihydroxybenzo(a)pyrene and 3,6-dihydroxychrysene. AB - Indirect evidence has suggested that multiple subunits of microsomal UDP glucuronosyltransferases (UGTs) are involved in diglucuronide formation of diphenols of polycyclic aromatic hydrocarbons (Bock et al., Mol Pharmacol 42: 613 618, 1992). To substantiate this suggestion functional target sizes of UGTs catalysing these reactions were determined in microsomes in situ by radiation inactivation analysis. Target sizes of UGTs catalysing the glucuronidation of 1 naphthol and 6-hydroxychrysene were found to be 91 +/- 29 and 120 +/- 27 kDa, respectively. However, target sizes for mono- and diglucuronide formation of 3,6 dihydroxybenzo(a)pyrene were 118 +/- 33 and 218 +/- 24 kDa, respectively. Similarly, using 3,6-dihydroxychrysene as substrate target sizes of 109 +/- 21 and 101 +/- 23 kDa were found for 6-O-monoglucuronide and 3-O-monoglucuronide formation and a target size of 192 +/- 34 kDa observed for diglucuronide formation. Based on subunit molecular masses of 50-60 kDa for UGTs, these results suggest that UGTs involved in monoglucuronide formation of phenols may function as dimers. In contrast, UGTs involved in diglucuronide formation of diphenols of polycyclic aromatic hydrocarbons may function as tetramers in microsomes in situ. PMID- 7980620 TI - Hepatic aldehyde and alcohol dehydrogenases in alcohol-preferring and alcohol avoiding rat lines. AB - The alcohol-avoiding ANA (Alko, Non-Alcohol) and alcohol-preferring AA (Alko, Alcohol) rat lines are known to differ in their acetaldehyde metabolism and were originally found to differ in hepatic alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) activities in the 1970s. At the beginning of the 1980s, these rat lines were revitalized and some previously found line differences were lost. Thus, the purpose of this study was to determine whether these enzymatic line differences still exist and, if so, to study them further at the isoenzyme level. ADH and ALDH activities were measured from liver homogenates and different subcellular fractions of the rats. The ANA rats were found to have lower hepatic ALDH and higher ADH activities than AA rats, in accordance with the previous study. The line difference in ALDH activity was observed in all fractions, but was more apparent with millimolar than micromolar substrate concentrations and generally more pronounced in females than in males. The line difference in the microsomal ALDH activity was found to be quantitative, and it seemed to concern both microsomal ALDH isoenzymes. A qualitative line difference concerning mitochondrial high Km ALDH isoenzyme was found, and three different cytosolic ALDH isoenzyme patterns were observed, the frequencies of which were found to be different in the two lines. In conclusion, the results of the present study support the assumption that line differences in hepatic ADH and ALDH activities may be relevant to the acetaldehyde accumulation and the particularly low ethanol consumption of the ANA rats. PMID- 7980621 TI - Differences in the kinetic properties, effect of calcium and sensitivity to inhibitors of paraoxon hydrolase activity in rat plasma and microsomal fraction from rat liver. AB - The properties of a rat hepatic microsomal enzyme that hydrolyses O,O-diethyl-p nitrophenylphosphate (paraoxon) were studied and compared to the paraoxon hydrolase activity found in rat plasma. The pH stability for both enzyme activities was optimum between pH 6.0 and 9.0. An overall analysis of the data showed that the microsomal fraction was less resistant to the effect of the pH than plasma. The kinetic constants for heat inactivation evaluated for paraoxonase in rat plasma and liver microsomal fraction indicate that paraoxonase tends to inactivate faster in rat liver microsomes than in rat plasma. The apparent activation energies of the heat inactivation process were 77.7 and 61.1 kcal/mol for rat plasma and microsomal fraction, respectively. Enzyme activity was lost after both dialysis and incubation with EDTA and partially restored by the addition of calcium. In rat plasma samples the requirement for calcium was absolute (essential activator) while in the microsomal fraction the reaction may occur, to a minimum extent, in the absence of the activator (non-essential activator). Calcium restored 85% activity when added immediately after EDTA; restored activity decreased when the time interval between addition of EDTA and calcium was increased. Other metals were not able to restore activity previously inhibited by EDTA or dialysis. The response to several inhibitors (EDTA, Mn, Co, Zn, Ba, Mg, Cu, La, Hg and p-hydroxy-mercuribenzoate) of rat plasma and microsomal fraction was studied, determining the type of inhibition and the inhibition constants. Plasma enzyme was always more resistant than liver sample to the effect of the inhibitors and showed different types of inhibition than the liver microsomal fraction. In general we found more differences than analogies between the rat plasma and liver enzyme which suggests the presence of two enzymes or two different forms of the same enzyme. Furthermore the existence of an EDTA-resistant fraction in rat liver microsomes suggests that more than one enzyme capable of hydrolysing paraoxon is present in the microsomal fraction of rat liver. PMID- 7980622 TI - Synergistic phosphorylation of the focal adhesion-associated vasodilator stimulated phosphoprotein in intact human platelets in response to cGMP- and cAMP elevating platelet inhibitors. AB - The mechanism underlying the synergistic inhibition of platelet activation by cGMP- and cAMP-elevating vasodilators was investigated using washed human platelets and platelet-rich plasma. With both types of human platelet preparations, low concentrations of sodium nitroprusside increased the cAMP elevating potency of low concentrations of prostaglandin E1 (PG-E1). Using threshold concentrations of both sodium nitroprusside and PG-E1, the NO-donor potentiated the effect of PG-E1 with respect to the phosphorylation of the focal adhesion-associated vasodilator-stimulated phosphoprotein (VASP) at serine157. In contrast, threshold concentrations of cell-membrane permeant selective activators of the platelet cGMP-dependent protein kinase or the cAMP-dependent protein kinase had only additive effects on VASP serine157 phosphorylation in washed human platelets. The data demonstrate that low intracellular levels of cGMP effectively inhibit type III cGMP-inhibited phosphodiesterase in human platelets despite the high levels of cGMP-dependent protein kinase present in this cell type. This study provides the first evidence that the simultaneous activation of both cGMP- and cAMP-dependent protein kinase results in additive effects on VASP serine157 phosphorylation, whereas the supra-additive effects observed with the combination of sodium nitroprusside and PG-E1 are due to cGMP-mediated inhibition of type III phosphodiesterase. VASP phosphorylation at serine157 may be an important component underlying the synergistic inhibition of human platelets by cGMP-and cAMP-elevating agents. PMID- 7980623 TI - Selectivity of isoprenoid-containing imidazole antifungal compounds for sterol 14 demethylase P450 (P450(14)DM) and 7-ethoxycoumarin O-deethylase P450 of rat liver microsomes. AB - The imidazole antifungal compound AFK-108 (1-[2-(2,4-dichlorophenyl)-2-((2E)-3,7 dimethylocta-2,6- dienyloxy)ethyl]-1H-imidazole) has been shown to be a potent inhibitor for yeast lanosterol 14 alpha-demethylase (P450(14)DM), interacting specifically with the sterol side-chain recognition part of the substrate site through its geranyl moiety. AFK-108 acted as a potent inhibitor for rat liver P450(14)DM, while its farnesyl (AFK-110) and prenyl (AFK-122) homologues were weak inhibitors. This indicates that AFK-108 interacts with rat liver P450(14(DM in the same manner as with the yeast enzyme. However, the difference between the potency of AFK-108 and the homologues was greater in rat P450(14)DM than in the yeast enzyme. AFK-108 and its homologues partially inhibited 7-ethoxycoumarin O deethylase activity of rat liver microsomes. The order of potency was AFK-122 > AFK-108 > AFK-110, indicating that some steric hindrance of the isoprenoid moiety might affect their potency. The inhibitory effect of AFK-108 for P450(14)DM was considerably higher than for 7-ethoxycoumarin O-deethylase P450, while the inhibition of AFK-110 and AFK-122 on these enzymes was of the same order of magnitude. These results suggest that azole compounds interacting with the side chain recognition site of P450(14)DM may be good candidates as antifungal agents selective for fungal P450(14)DM. PMID- 7980624 TI - Distamycin analogues with improved sequence-specific DNA binding activities. AB - In the present study we have investigated the effect of unprecedented chemical modifications introduced in the distamycin molecule, with the aim of assessing their ability to interfere with sequence-specific DNA-protein interactions in vitro. By using an electrophoretic mobility shift assay, we have been able to identify novel distamycin analogues with improved displacing abilities on the binding of octamer nuclear factors to their target DNA sequence. While variations in the number of pyrrole rings and/or reversion of an internal amide bond result in distamycin-like compounds with identical or very similar properties, the reversion of the formamido into a carboxyamido group or its replacement with the charged formimidoyl moiety significantly improves the ability of the resulting novel distamycin derivatives to compete with OCT-1 (octamer 1 nuclear factor) for its target DNA sequence. Tissue-specific octamer-dependent in vitro transcription is similarly affected by these chemical modifications, suggesting that the ability of distamycins to bind octamer sequences has a direct influence on the functional state of octamer-containing promoters. These data represent an initial, successful attempt to rationalize the design of DNA binding drugs, using distamycins as a model. PMID- 7980625 TI - Metabolic and radiolytic reduction of 4-alkylamino-5-nitroquinoline bioreductive drugs. Relationship to hypoxia-selective cytotoxicity. AB - The 4-alkylamino-5-nitroquinolines (5NQs) are a new series of bioreductive drugs that exhibit varying degrees of selective toxicity (up to 60-fold) under hypoxic conditions in cell culture. This study tested the hypothesis that differences in hypoxia-selective cytotoxicity in this series reflect differences in the efficiency with which oxygen inhibits metabolic reduction. The products of reduction of six 5NQs were characterized and rates of reduction compared in aerobic and hypoxic AA8 cells. The major stable products of both radiolytic and metabolic reduction under anoxic conditions were the corresponding amines, which were not responsible for the toxicity of the parent nitro compounds. Metabolism of each compound was inhibited completely in aerobic cells, indicating that differences in hypoxia-selective toxicity in this series are not due to variations in efficiency as substrates for oxygen-insensitive nitro reduction. Rates of hypoxic metabolism correlated broadly with hypoxia-selective cytotoxicity; the 5NQ derivatives with high rates of hypoxic metabolism had good hypoxia-selective cytotoxicity, whereas the compounds with low rates of reduction (the 3,6-dimethyl and 8-methylamino compounds; 3,6diMe-5NQ and 8NHMe-5NQ) were non-selective. Low rates of drug-induced oxygen consumption by 3,6-diMe-5NQ and 8NHMe-5NQ in respiration-inhibited cells confirmed that these compounds are poor substrates for enzymatic nitro reduction. While there was an overall correlation between one-electron reduction potential at pH 7 (E1(7)) and rate of metabolic reduction, the relatively high E1(7) of 3,6diMe-5NQ (-367 mV) indicates that rates of reduction, and hypoxic selectivity of cytotoxicity, cannot be predicted from reduction potential alone. 3,6diMe-5NQ and 8NHMe-5NQ are cytotoxic through a non-bioreductive mechanism, the variable contribution of which may underlie the differences in hypoxia-selective cytotoxicity within this series of bioreductive drugs. PMID- 7980626 TI - Selective inhibition of cyclooxygenase 2. AB - Cyclooxygenase (COX), a key enzyme in the formation of prostanoids, is known to exist in two isoforms: an inducible enzyme (COX 2) and a constitutive from (COX 1). Both enzymes are inhibited by non-steroidal anti-inflammatory drugs (NSAID), but only marginal selectivity has thus far been reported. In this study, we report on a novel selective inhibitor of COX 2, CGP 28238 (6-(2,4 difluorophenoxy)-5-methyl-sulfonylamino-1-indanon e). Human washed platelets were used as a source of COX 1. For IL-1 stimulated rat mesangial cells we demonstrated the almost exclusive presence of COX 2 in western blot and mRNA analysis. Therefore these two model systems were chosen for selectivity testing. With an IC50 value of 15 nM, CGP 28238 blocked COX 2 activity in a similar concentration range to that of other potent NSAID such as indomethacin and diclofenac (IC50 = 1.17-8.9 nM). However, in contrast to these reference NSAIDs, CGP 28238 was at least 1000-fold less potent in inhibiting COX 1. Using other cell systems reported to express COX 1 or COX 2, we obtained a similar selectivity for COX 2. Thus, on the basis of our findings, CGP 28238 is a novel, highly potent and selective inhibitor of COX 2 and may be a lead compound for a new generation of potent anti-inflammatory drugs with an improved side-effect profile. PMID- 7980627 TI - Molecular effects of 2',2'-difluorodeoxycytidine (Gemcitabine) on DNA replication in intact HL-60 cells. AB - The ability of pH-step alkaline elution to isolate different size species of nascent DNA (nDNA) from intact cells was utilized to study the effects of 2',2' difluorodeoxycytidine (dFdC) on DNA replication in HL-60 cells. Preincubation with dFdC caused a concentration-dependent decrease in overall [3H]thymidine incorporation into DNA, accompanied by an increase in the proportion of radiolabel accumulated in small nDNA fragments. Twenty-four hours following removal of dFdC, radiolabel progressed from smaller to larger fragments and into genomic-length DNA. At initial concentrations of exposures to dFdC or cytosine arabinoside (ara-C) that caused 50% lethality (LC50) to HL-60 cells (40 and 50 nM, respectively), slower and less complete transit of nDNA from small subreplicon-length fragments through larger intermediates to genomic-length DNA was observed for nDNA fragments containing incorporated [3H]dFdC than for fragments containing [3H]ara-C. This was accomplished with less [3H]dFdC incorporated into DNA than [3H]ara-C at these extracellular concentrations of drug. Pulse-chase studies, using higher concentrations of radiolabeled drug, similarly revealed that nDNA fragments containing incorporated dFdC, like those containing ara-C, progressed with respect to time into larger nDNA intermediates and ultimately into genomic-length DNA; however, such progression for nDNA fragments containing dFdC was less complete than for fragments containing ara-C. The radioactivity incorporated into DNA represented authentic dFdC, as determined by DNA degradation studies, and was stable in DNA for at least 48 hr after removal of extracellular [3H]dFdC. Some of the effects of dFdC on ribonucleotide reduction in HL-60 cells were assessed by measurement of the intracellular pools of dCTP and dGTP. The drug had a greater effect on pools of dGTP than of dCTP, with transient reductions in dGTP observed at concentrations that encompass the LC50 for dFdC. These studies suggest that the interaction with DNA synthesis is an important component of the cytotoxicity of dFdC in HL-60 cells. Because it is incorporated progressively through nDNA compartments and ultimately into genomic length DNA, dFdC should be categorized as an agent that slows DNA elongation in the intact cell, and not as a chain terminator in the absolute sense. PMID- 7980628 TI - Mechanism of protection of ebselen against paracetamol-induced toxicity in rat hepatocytes. AB - The protective effect of ebselen (PZ 51), an anti-inflammatory agent, on paracetamol-induced (1 mM) cytotoxicity in hepatocytes freshly isolated from beta naphthoflavone-pretreated rats was studied. At a concentration of 50 microM added simultaneously with paracetamol, ebselen prevented paracetamol-induced leakage of lactate dehydrogenase (LDH) almost completely and lipid peroxidation (LPO) and depletion of glutathione (GSH) substantially. These protective effects were even more pronounced at 100 microM concentration of ebselen. When added to the hepatocytes 1 hr before paracetamol, 50 microM of ebselen also prevented LDH leakage, LPO and GSH depletion. Reverse addition of paracetamol and ebselen did not result in protection. Simultaneous incubation of 100 microM ebselen and paracetamol inhibited GSH conjugation of paracetamol by more than 50%, however, without any effect on glucuronidation and sulfation of paracetamol. Ebselen was shown not to react directly with paracetamol nor to inhibit cytochrome P450 activity measured as 7-ethoxycoumarin O-deethylase (ECD) activity in the hepatocytes. At mixing, synthetic ebselen selenol and synthetic N-acetyl-p benzoquinone imine (NAPQI) were shown to form paracetamol and ebselen diselenide. No indication was found for the formation of an ebselen-paracetamol conjugate upon reacting synthetic NAPQI and synthetic ebselen selenol. Reduction of NAPQI, the reactive metabolite of paracetamol, by ebselen selenol is discussed in terms of the mechanism of cytoprotection. PMID- 7980629 TI - Expression and function of multidrug resistance P-glycoprotein in a cultured natural killer cell-rich population revealed by MRK16 monoclonal antibody and AHC 52. AB - Natural killer (NK) cells have been reported recently to be the highest in expressing multidrug resistance (MDR) P-glycoprotein among normal mature lymphoid cells. Using a cultured NK cell-rich population, we have examined the expression and function of P-glycoprotein, in particular its role in NK cell-mediated cytotoxicity, by employing two MDR-reversing agents (nicardipine and AHC-52, a nicardipine analog almost devoid of calcium channel blocking activity) and monoclonal antibody against P-glycoprotein (MRK-16). The expression of P glycoprotein was detected by flow cytometry and polymerase chain reaction of reverse transcribed mRNA. P-glycoprotein was functional in terms of rhodamine dye excretion and its susceptibility to the MDR-reversing agents. Since the concentration of nicardipine required for 50% inhibition (IC50) of rhodamine dye excretion (2 microM) was close to that of AHC-52 (5 microM), it was suggested that their inhibitory effects were not due to calcium channel blocking activity, and that ACH-52 is a selective inhibitor for P-glycoprotein. The IC50 of nicardipine for NK cell-mediated cytotoxicity (33 microM) was also close to that of AHC-52 (26 microM), indicating that P-glycoprotein is involved in NK cell mediated cytotoxicity. In support of this, MRK16 inhibited NK cell-mediated cytotoxicity in a concentration-dependent manner. Both binding of target cells to NK cells and post-binding events were affected by AHC-52, suggesting that P glycoprotein is involved in several steps in NK cell-mediated cytotoxicity. PMID- 7980630 TI - Induction of lipocortin 1 by topical steroid in rat skin. AB - Western blotting and densitometric analysis of extracts obtained from EDTA extraction of skin segments showed greater extracellular Lipocortin 1 (LC1) in skin sites from steroid-treated animals compared to that seen in matched vehicle treated animals. Extracellular LC1 was maximal 3 hr after steroid, less was found in skin after 6 hr and levels had returned to basal at 18 hr. Pre-treatment of rats with the glucocorticoid receptor antagonist RU38486 (20 mg/kg) prevented the steroid induction of extracellular LC1 at both the 3 and 6 hr time-points. Systemic treatment of rats with betamethasone sodium phosphate (0.1-1 mg/kg) showed that the induction of LC1 on the cell surface was both time- and dose dependent. Oedema in rat skin caused by 5-hydroxytryptamine (5-HT), platelet activating factor (PAF) and zymosan activated serum (ZAS) was assessed using 125I labelled human serum albumin. Following a 3 hr topical treatment with betamethasone-17-valerate the inflammatory activities of all of the tested stimuli were significantly attenuated demonstrating that at this time-point the topical steroid was biologically active. Topical steroid treatment of the skin resulted in a translocation of LC1 to the cell surface, which was maximal after a 3 hr period and was also temporally associated with the anti-inflammatory effect of these agents. PMID- 7980631 TI - Effects of perphenazine on the metabolism of inositol phospholipids in SK-N-BE(2) human neuroblastoma cells. AB - Administration of myo-[3H]inositol to SK-N-BE(2) human neuroblastoma cells for 24 hr resulted in equilibrium labelling of phosphatidylinositol (PI), phosphatidylinositol 4-phosphate (PIP) and phosphatidylinositol 4,5-bisphosphate (PIP2), as well as in retention of a large intracellular pool of free myo [3H]inositol. Equilibrium labelling was no longer observed when cells were treated for 2 hr with 20 microM perphenazine (PPZ) in label-free medium; under these conditions, myo-[3H]inositol from the retained intracellular pool was incorporated into PI and PIP but not into PIP2. Analysis of water-soluble myo [3H]inositol derivatives and inositol 1,4,5-trisphosphate mass determination indicated that PPZ did not stimulate phosphoinositide hydrolysis by phospholipase C. These results indicate that PPZ raises PI and PIP levels, whereas it is ineffective in expanding the PIP2 pool. The latter effect is not due to a concomitant synthesis and hydrolysis of this lipid. PMID- 7980632 TI - Binding characteristics of the adenosine A2 receptor ligand [3H]CGS 21680 to human platelet membranes. AB - The binding characteristics of the selective adenosine A2 agonist [3H]CGS 21680 ([3H]2-[p-(2-carboxyethyl)-phenethyl-amino]-5'-N- ethylcarboxamidoadenosine) were determined in human platelet membranes. Specific binding was saturable, reversible and dependent upon protein concentration. Saturation experiments revealed a single class of binding sites with Kd and Bmax values of 1.4 microM and 5.9 pmol/mg of protein, respectively. Adenosine receptor agonists and antagonists competed for the binding of [3H]CGS 21680 (50 or 200 nM) to human platelet membranes showing a rank order of potency consistent with that typically found for interactions at the adenosine A2 receptor. Adenylate cyclase stimulation and platelet aggregation inhibition induced by adenosine agonists exhibited a rank order of potency close to that observed in binding experiments. However, the adenosine A1 receptor agonists, R- and S-N6-(2 phenylisopropyl)adenosine, (R-PIA) and (S-PIA), N6-cyclohexyladenosine (CHA) and 2-chloro-N6-cyclopentyladenosine (CCPA), which stimulate adenylate cyclase and inhibit platelet aggregation in the low microM range, displaced [3H]CGS 21680 only in the high microM range. In conclusion, we have found that [3H]CGS 21680, which is widely used as a specific A2 agonist in binding studies on brain tissues, is not appropriate for the characterization of the human platelet adenosine A2 receptor. PMID- 7980633 TI - Heterogeneous repair of platinum-DNA adducts by protein extracts from mammalian tissues. AB - Cis-diamminedichloroplatinum (II) (cisplatin) is a mainstay of human cancer chemotherapy. In addition to its antitumour effects however, cisplatin is toxic to normal tissues, causing dose-limiting nephrotoxicity and neurotoxicity. On the other hand, myelosuppression is uncommon. In the light of data suggesting a role for DNA repair mechanisms as determinants of cellular cisplatin sensitivity, we postulated that varying DNA repair capacities between tissues could explain the patterns of organ toxicity seen in clinical practice. Using a novel cell-free assay of repair of cisplatin-DNA adducts, we find that the DNA repair capacity of protein extracts from different tissues varies significantly in our assay, but does not directly correlate with the organ toxicity profile of cisplatin. PMID- 7980634 TI - Endogenous substrates and functional role of eukaryotic mono(ADP-ribosyl) transferases. PMID- 7980635 TI - Serotonin inhibition of adenylate cyclase in human platelet membranes; relation to 5-HT-1A receptor-mediated activity. AB - Serotonin inhibited both basal and forskolin-stimulated adenylate cyclase activity in human platelet membranes by approx. 30%, with an EC50 of 54 nM. Addition of NaCl to the assay medium reduced the degree of inhibition. 5 carboxamidotryptamine (5-CT) behaved as a full agonist in this system (EC50 of 5.4 nM) and BMY 7378 as a partial agonist (inducing 19% inhibition); the putative 5-HT-1a receptor agonists metergoline, spiroxatrine and MDL 73005 were inactive. The 5-HT-1a receptor antagonists metitepin and NAN-190 behaved as antagonists with Kb or Ki values of 11.2 and 1.17 nM, respectively. Spiperone behaved as a partial antagonist only. Epinephrine and 5-HT produced convergent, non-additive inhibition of both basal and forskolin-stimulated cyclase. PMID- 7980636 TI - Role of thiol homeostasis and adenine nucleotide metabolism in the protective effects of fructose in quinone-induced cytotoxicity in rat hepatocytes. AB - Freshly-isolated rat hepatocytes were exposed in glucose (15 mM) or fructose (5 mM) medium to menadione (2-methyl-1,4-naphthoquinone) (85 microM) or 1,4 naphthoquinone (NQ) (50 microM). Menadione and NQ are closely related quinones and have an approximately equal potential to induce redox cycling. However, NQ has a higher potential to arylate and is more toxic than menadione. During 2 hr of incubation, cell viability, thiol status, adenine nucleotide level and lactate production were determined. LDH-leakage was used as a measure of cell viability. In glucose medium, exposure of hepatocytes to menadione or NQ resulted in a faster excretion rate of oxidized glutathione as compared to those cells in fructose medium. As a result, quinone-exposed hepatocytes in fructose medium retained higher amounts of oxidized glutathione. Menadione-exposed hepatocytes in fructose medium exhibited a diminished rate of transthiolation of protein thiols with oxidized glutathione as compared to those cells in glucose medium. The adenine nucleotide level of hepatocytes in glucose medium was markedly higher than in fructose medium. This was caused by an ATP decrease in hepatocytes in fructose medium resulting in a low energy charge (E.C.) (0.6) as compared to hepatocytes in glucose medium (0.9). Only menadione caused a decrease in the E.C. in glucose medium while NQ caused a decrease of all three adenine nucleotides. In fructose medium, quinone-exposed hepatocytes showed no change in their adenine nucleotides as compared to control cells. Despite the higher oxidized glutathione content and the lower ATP level of NQ-exposed hepatocytes in fructose medium, they had a better viability than those cells in glucose medium. From our results we conclude that a high ATP content is not always beneficial for cell survival. PMID- 7980637 TI - Stereoselective binding of the glucuronide of ketoprofen enantiomers to human serum albumin. AB - Since acyl glucuronides are known to undergo deconjugation, especially in the presence of human serum albumin (HSA), only a few reports have described their reversible binding to plasma proteins. The aim of this study was to investigate the reversible binding of R and S ketoprofen glucuronides to HSA by a rapid technique, such as ultraviolet circular dichroism. Binding of R ketoprofen glucuronide only induced an extrinsic Cotton effect at 340 nm. Scatchard plot analysis revealed that R ketoprofen and its glucuronide are bound to one site of albumin with an association constant of 28.1 x 10(4) and 6.1 x 10(4) M-1, respectively. Modification of one tyrosine residue by diisopropylfluorophosphate prevented the access of ligands to sites I and II of albumin, and also fully inhibited the binding of R ketoprofen and that of its conjugate. Displacement experiments with specific probes of albumin binding sites suggested that R ketoprofen and the glucuronide are bound to site II rather than site I. However, R ketoprofen was not displaced by its conjugate. S ketoprofen glucuronide is also bound to HSA, since it decreased the binding of the antipode conjugate. However, the binding of this metabolite to albumin did not induce an extrinsic Cotton effect large enough to determine the binding constants. D-Glucuronic acid did not bind to sites I or II of albumin. This moiety is likely responsible for the lower affinity of HSA for the R ketoprofen glucuronide when compared to that for R ketoprofen, due to the hydrophilicity and/or the bulkiness of this group. PMID- 7980638 TI - The induction/loss of the oxidant-resistant phenotype of Chinese hamster ovary (CHO) cell variants does not correlate with sensitivity to DNA single strand breakage by hydrogen peroxide. AB - Hydrogen peroxide resistant variants of Chinese hamster ovary (CHO) cells characterized by different levels of resistance to growth inhibition induced by the oxidant displayed a decreased susceptibility to the induction of DNA single strand breakage by hydrogen peroxide. Resistance to DNA damage, however, was maximal in cells resistant to killing by low concentrations of H2O, and did not increase further in cells characterized by a much higher resistance to the toxic action of the oxidant. Different sensitivities to the induction of DNA single strand breakage observed in wild type and resistant sublines were related to a decreased susceptibility/differential depletion of H2O2, rather than being dependent on different velocities in DNA repair processes. Growth of resistant cells in the absence of H2O2 resulted in a rapid loss of resistance to induction of DNA strand scission by H2O2. Cells retained resistance to the growth inhibitory effect of the oxidant under conditions where resistance to the production of DNA single strand breaks was lost. Experiments aimed at elucidating the molecular basis for resistance to DNA damage induction by H2O2 have demonstrated that this effect is dependent upon the catalase activity of the specific sublines as well as on their different total protein content. PMID- 7980639 TI - Effect of different oxygen pressures and N,N'-diphenyl-p-phenylenediamine on Adriamycin toxicity to cultured neonatal rat heart myocytes. AB - The effect of different oxygen pressures and the antioxidant DPPD (N,N'-diphenyl p-phenylenediamine) on Adriamycin (doxorubicin) cytotoxicity in highly purified cardiac myocytes was investigated to evaluate the involvement of free radicals in the mechanism of toxicity. Adriamycin exposure caused a time-dependent decrease in viability measured as intracellular potassium ion release or lactate dehydrogenase retention. Incubation of myocytes in 16, 172 or 834 microM oxygen during exposure to 200 microM Adriamycin for 6 hr killed 13, 42 and 56% of the cells in the respective cultures. DPPD prolonged viability in the latter two oxygen concentrations and protected against lipid peroxidation measured as production of malondialdehyde and 4-hydroxynonenal. Addition of superoxide dismutase decreased the Adriamycin-induced cell killing to 6% after a 4-hr incubation, as compared to 24% in cultures exposed to Adriamycin only. Adriamycin exposure decreased the concentration of reduced glutathione, and the toxicity of the drug was increased when glutathione reductase was inhibited by the addition of BCNU (1,3-bis-2-chloroethyl-1-nitrosourea). No significant effect on Adriamycin toxicity was observed after inhibition of glutathione synthesis by treatment with BSO (buthionine sulfoximine). It is concluded that free radicals play an important role in Adriamycin toxicity to heart myocytes, and that the cell killing mechanism is likely to be related to induction of lipid peroxidation. PMID- 7980640 TI - pNAT and CYP2D6 gene polymorphism in epileptic patients. AB - Certain anticonvulsant drugs require N-acetylation as a major route of metabolic clearance. Single point mutations of the polymorphic N-acetyltransferase gene (pNAT) are the primary cause for impaired drug acetylation. Pharmacokinetic parameters are altered in slow acetylator phenotypes and this may compromise drug safety. Genetic analysis of allelic frequencies of individual pNAT genotypes point to significant increases in carriers of the S1/wt and S3/wt (P < 0.05) allele and a significant reduction in carriers of the S2/S2 (P < 0.01) allele, when control and epileptic patients are compared. Furthermore, the presumed link between the cytochrome P450 CYP2D6 polymorphism and the pathogenesis of Parkinson's disease led us to investigate, whether a similar relationship can be expected for other CNS disorders. Our findings indicate that poor metabolizers are more frequent (P < 0.05) amongst epileptic patients, when compared with a control population. An estimate of the odds ratio may suggest an increased risk [95% CI (confidence interval) 1.043-4.734] of up to 5-fold in epileptic patients carrying this mutation. This provides further evidence for a potential link between the debrisoquine hydroxylase gene polymorphism and CNS disorder and therefore warrants further study. PMID- 7980641 TI - Selective potentiation of histamine H1-receptor stimulated calcium responses by 1,4-dithiothreitol in DDT1MF-2 cells. AB - The effect of 1,4-dithiothreitol (DTT) on agonist-stimulated increases in intracellular free calcium concentration ([Ca2+]i) has been investigated in the smooth muscle cell line, DDT1MF-2, derived from hamster vas deferens. Pretreatment with DTT (1 mM) produced a large leftward parallel shift in concentration-response curve for histamine H1-receptor mediated increases in [Ca2+]i. The EC50 values for H1-receptor stimulated increases in [Ca2+]i in the absence and presence of DTT were 11.3 +/- 1.5 microM (N = 6) and 0.52 +/- 0.15 microM (N = 6), respectively. DTT had no significant effect on the maximum Ca2+ response elicited by histamine (100 microM). In the presence of DTT the partial H1-receptor agonist 2-pyridylethylamine (100 microM) increased [Ca2+]i from 112 +/- 14 nM to 237 +/- 24 nM (N = 10). In control cells 2-pyridylethylamine (100 microM) did not elicit a Ca2+ response. DTT had no significant effect on the maximum Ca2+ response elicited by 1 mM 2-pyridylethylamine. The enhancement of histamine H1-receptor Ca2+ responses by DTT was reversed by the sulphydryl oxidizing agent dithiobis-(2-nitrobenzoic acid). DTT had no significant effect on adenosine A1-, bradykinin and ATP-receptor stimulated increases in [Ca2+]i. [3H]mepyramine binding experiments confirmed that DTT increased agonist affinity. DTT produced a small, but significant, leftward shift in concentration-response curve for histamine displacement of [3H]mepyramine binding. These data suggest that DTT potentiates H1-receptor mediated Ca2+ responses by increasing agonist affinity. PMID- 7980642 TI - Antisense oligonucleotides to human lipocortin-1 inhibit glucocorticoid-induced inhibition of A549 cell growth and eicosanoid release. AB - Glucocorticoids actively inhibit the growth of A549 cells by suppressing the release of factors such as prostaglandin E2 (PGE2) necessary for their proliferation. This effect is largely mediated through induction of the protein lipocortin-1. We now show that transient transfection of A549 cells with an antisense DNA oligonucleotide targeted to a region coding the unique N-terminal portion of human lipocortin-1 blocks the induction of lipocortin-1 protein following glucocorticoid treatment and completely reverses glucocorticoid-induced suppression of cell proliferation and PGE2 release. A scrambled oligonucleotide was without effect. Continued culture of A549 cells in the presence of this oligonucleotide results in a sustained increase in cell proliferation and PGE2 release. This study reinforces the importance of lipocortin-1 as a negative modulator of cell growth and eicosanoid generation in this system. PMID- 7980643 TI - Induction of cytochrome P450 isozymes in rat renal microsomes by cyclosporin A. AB - To examine the effects of cyclosporin A (CsA) on renal cytochrome P450 forms, CsA was administered to rats, and the renal levels of P450 were determined by immunoblotting. CsA treatment for 17 days increased total renal P450 content by 40% with a concomitant elevation of the omega- and (omega-1)-hydroxylation activities of lauric acid. Arachidonic acid omega-hydroxylation activity was also induced 2-fold by treatment with CsA for 17 days. Among the P450 forms, CYP4A2 was induced significantly, whereas CYP2C23, CYP4A1 and CYP4A8 were unaffected. These changes were accompanied by slight but significant increases in blood urea nitrogen and systolic blood pressure. These data suggest that CsA increased arachidonic acid omega-hydroxylation activity by the induction of CYP4A2. The specific induction of CYP4A2 may be related to CsA-induced nephrotoxicity and elevated blood pressure, because omega-hydroxyarachidonic acid is a potent vasoconstrictor. PMID- 7980644 TI - Purification and characterization of a human liver cocaine carboxylesterase that catalyzes the production of benzoylecgonine and the formation of cocaethylene from alcohol and cocaine. AB - The psychomotor stimulant cocaine is inactivated primarily by hydrolysis to benzoylecgonine, the major urinary metabolite of the drug. A non-specific carboxylesterase was purified from human liver that catalyzes the hydrolysis of the methyl ester group of cocaine to form benzoylecgonine. In the presence of ethanol, the enzyme also catalyzes the transesterification of cocaine producing the pharmacologically active metabolite cocaethylene (benzoylecgonine ethyl ester). The carboxylesterase obeys simple Michaelis-Menten kinetics with Km values of 116 microM for cocaine and 43 mM for ethanol. The enzymatic activity suggests that it may play an important role in regulating the detoxication of cocaine and in the formation of the active metabolite cocaethylene. Additionally, the enzyme catalyzes the formation of ethyloleate from oleic acid and ethanol. The carboxylesterase was purified from autopsy liver by gel filtration, chromatofocusing, ion-exchange, and hydrophobic interaction chromatography to purity by SDS-PAGE and agarose gel isoelectric focusing. The subunit molecular weight was determined to be 59,000 and the native molecular weight was estimated to be 170,000 from a calibrated gel filtration column, suggesting that the active enzyme is a trimer. The isoelectric point was approximately 5.8. Digestion of carbohydrate residues on the protein with an acetylglucosaminidase plus binding to several lectins indicates that the enzyme is glycosylated. The esterase was cleaved with two proteases, and the amino acid sequences from fourteen peptides were used to search GenBank. Two identical matches were found corresponding to carboxylesterase cDNAs from human liver and lung. PMID- 7980645 TI - Acute pneumocyte injury, poly(ADP-ribose) polymerase activity, and pyridine nucleotide levels after in vitro exposure of murine lung slices to cyclophosphamide. AB - Cyclophosphamide (CYC) is a metabolically activated, DNA-alkylating, antitumor agent that causes pulmonary fibrosis. BALB/cN (B) mice are sensitive and C57Bl/6N (C) mice are resistant to CYC-induced fibrosis. Pulmonary bioactivation may contribute to strain sensitivity. Therefore, we tested the intrinsic susceptibility of murine lung slices to cell injury by direct exposure to CYC for 2-8 hr. Injury was measured by release of lactate dehydrogenase (LDH). DNA damage activates the nuclear enzyme poly(ADP-ribose) polymerase (PAP, EC 2.4.2.30), causing depletion of its substrate, NAD. NAD can also be decreased by phosphorylation to NADP, as seen with oxidative stress. Depletion of NAD can lead to loss of ATP. Thus, we measured LDH release, PAP activation, NAD, NADP and ATP in slices incubated with or without the PAP-inhibitor, 3-aminobenzamide (3-AB). CYC (0.1 to 1.0 mg/mL for 4-8 hr) caused LDH release in slices from both murine strains, but LDH release was significantly greater in B lung slices than in C slices. After an 8-hr incubation 63.9 +/- 3.7% (mean +/- SEM) of total LDH was released from B lung slices with 1.0 mg CYC/mL, whereas only 45.8 +/- 2.6% was released from C lung slices (P < 0.05). 3-AB reduced LDH release to 44.7 +/- 2.4% in B slices and 28.1 +/- 2.0% in C slices (P < 0.05 vs CYC only). PAP activity in nuclei isolated from CYC-treated B lung slices was increased 2- to 4-fold after 2 hr of incubation with 0.5 and 1.0 mg CYC/mL. PAP activation was delayed and reduced with incubation in 3-AB. PAP was activated 2-fold in nuclei from C slices treated with 0.5 mg CYC/mL for 2 hr. NAD was decreased at 2 and 4 hr in B slices treated with 0.5 and 1.0 mg CYC/mL, and at 4 hr with 0.1 mg CYC/mL. NAD depletion occurred only at 4 hr in the resistant C slices treated with 1.0 mg CYC/mL. CYC increased NADP by a similar extent in B and C lung slices. In B slices, NAD losses were approximately 4 times the increases in NADP. CYC did not decrease ATP in B slices and ATP dropped 25% only after 4 hr in the resistant C slices. We conclude that CYC is directly toxic to lung tissue and observe that strain sensitivity in vitro mirrors the sensitivity to fibrosis in vivo. PAP activation and oxidative stress may contribute to this toxicity. PMID- 7980646 TI - Interaction of the regulatory domains of the murine Cyp1a1 gene with two DNA binding proteins in addition to the Ah receptor and the Ah receptor nuclear translocator (ARNT). AB - The aromatic hydrocarbon (Ah) receptor complex is a ligand-activated transcriptional activator consisting of at least two protein components. The ligand-binding component is the AhR protein, a cytosolic receptor encoded by the Ahr gene, which, upon ligand binding, translocates to the nucleus in a heterodimeric complex with the ARNT (Ah receptor nuclear translocator) component. The complex binds to several discrete DNA domains containing aromatic hydrocarbon responsive elements (AhRE) present in the regulatory region of the murine cytochrome P(1)450 Cyp1a1 gene and of the other genes in the [Ah] gene battery. As a consequence of binding, a transcriptional complex is formed that activates the expression of these genes by as yet unidentified mechanisms. We have analyzed DNA-protein interactions in four of these domains, specifically, the AhREs located between -1085 and -482 (sites A, C, E, and D) of the upstream regulatory region of the murine Cyp1a1 gene. We found that two DNA-binding proteins, present in cytosolic and nuclear extracts of mouse Hepa-1 cells, showed overlapping DNA binding specificities to those of the Ah receptor. One of these proteins had an apparent molecular mass of 35-40 kDa, bound only to AhRE3 (site D), and has been identified tentatively as a member of the C/EBP family of transcription factors. The second protein, purified by DNA-affinity chromatography, had an apparent molecular mass of 95 kDa and bound to a larger DNA motif that included the AhRE sequence, in AhRE3 and AhRE5 (sites D and A), but not in AhRE1 or AhRE2 (sites C and E). This protein was not AhR nor was it ARNT, since it was found in receptorless (Ahr-) and in nuclear translocation-defective (Arnt-) cells, as well as in cells that had not been exposed to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD; dioxin), a potent inducer of Cyp1a1 expression. Evidence from in vivo methylation protection indicated that two G residues flanking AhRE3, one of which is required for binding of the 95-kDa protein, may be protected from methylation in uninduced cells and become exposed upon dioxin treatment, suggesting that the 95-kDa protein may be constitutively bound to AhRE3, and be displaced by binding of the Ah receptor complex. These results lend support to the concept that the transcriptional regulation of the [Ah] battery genes could be modulated by combinatorial interactions of the Ah receptor complex with other transcription factors. PMID- 7980647 TI - Characterisation of praziquantel metabolism by rat liver microsomes using cytochrome P450 inhibitors. AB - The metabolism of praziquantel (PZQ) was studied in microsomes isolated from livers of differently pretreated rats and in the presence of various inhibitors of cytochrome P450 (P450) isoforms. Microsomes from phenobarbitone (PB) pretreated rats metabolised PZQ to its major metabolite 4OH-praziquantel (4OH PZQ) at a greater rate than those from 20-methylcholanthrene (MC) and saline (SA) pretreated rats. The Vmax for the PB microsomes was 600 nmol 4OH-PZQ formed/mg/min x 10(-3) compared to 91.4 nmol/mg/min x 10(-3) for MC and 238 nmol/mg/min x 10(-3) for SA microsomes. These results indicate that PZQ is metabolised by PB-inducible isoforms of P450. Inhibitor studies were conducted with microsomes from SA-pretreated animals. In these studies, caffeine, disulfuram, and tolbutamide were poor inhibitors of the metabolism of PZQ to 4OH PZQ, with I50 values not determinable. Quinidine and quinine inhibited the hydroxylation of PZQ but with high Ki values. 17 alpha-Ethynylestradiol, cimetidine and diphenylhydramine were effective inhibitors of the formation of 4OH-PZQ, with 17 alpha-ethynylestradiol being the most potent with a Ki of 0.5 +/ 0.05 microM. From the known specificities of these P450 inhibitors, it is therefore concluded that cytochromes P450 1A2, 2E1, 2C9-10, and 2D6 probably do not contribute significantly to the metabolism of PZQ to its major metabolite in rats. It is likely that cytochromes P450 2B1 and 3A, both inducible by PB, are predominantly responsible for the formation of 4OH-PZQ. PMID- 7980648 TI - Subcellular distribution of the alpha and beta topoisomerase II-DNA complexes stabilized by VM-26. AB - Studies were done to determine (a) the subcellular distribution of the alpha (170 kDa) and beta (180 kDa) isozymes of topoisomerase II, and (b) the extent to which each isozyme forms complexes with DNA in tumor cells incubated with and without VM-26. Western blotting revealed that topoisomerase II beta was highly unstable during cell fractionation. However, preincubation of human CEM leukemia cells with 5-100 microM VM-26 for 30 min protected the beta isozyme from degradation by progressively increasing the amount of this isoform bound to DNA. The amount of topoisomerase II beta detected in nuclei of CEM cells incubated for 30 min with 25 microM VM-26 was 7-fold greater than in nuclei from untreated control cells. VM-26 also had a protective effect on topoisomerase II beta in HL-60 leukemia and WiDR colon carcinoma cells. In contrast, the intercalating agents mitoxantrone and m-AMSA did not protect topoisomerase II beta from degradation during cell fractionation. The stabilization of topoisomerase II beta by VM-26 allowed subsequent studies of the subcellular distribution of the topoisomerase II isozymes. Both isozymes were detected in the nonmatrix (high salt-soluble) fraction of nuclei from CEM cells, but only topoisomerase II alpha was present in the nuclear matrix. VM-26 stabilized binding of the alpha and beta topoisomerase II isoenzymes to nonmatrix DNA and topoisomerase II alpha to matrix DNA. The differences observed in the subnuclear distribution and DNA binding pattern of the topoisomerase II isozymes support the hypotheses that each isozyme has a distinct cellular function, and that both the alpha and beta isozymes are potential targets for VM-26 in intact cells. In addition, the results demonstrated that pretreatment of various cell lines with VM-26 is a useful way to stabilize topoisomerase II beta during cell fractionation. PMID- 7980649 TI - 3'-Azido-3'-deoxythymidine cytotoxicity and metabolism in the human colon tumor cell line HCT-8. AB - We have reported that 3'-azido-3'-deoxythymidine (AZT) possesses significant cytotoxicity in human tumor models when combined with agents that inhibit de novo thymidylate (dTMP) synthesis, such as 5-fluorouracil (FUra) and methotrexate (MTX). To aid in the further development of these and related cancer chemotherapeutic regimens, this study was undertaken to identify the biochemical processes relevant to the induction of AZT cytotoxicity in the model human colon tumor cell line HCT-8. The IC50 of AZT in this cell line after a 5-day exposure was 55 microM. In cells incubated for 5 days with various concentrations of [3H]AZT alone, both [3H]AZT nucleotide pools and [3H]AZT incorporation into DNA increased as the concentration of AZT in the medium increased. In addition, a 5 day exposure to AZT, at medium concentrations < or = 100 microM, resulted in a reduction in dTMP synthase (EC 2.1.1.45; methylene tetrahydrofolate:deoxyuridine 5'-monophosphate C methyltransferase) and dTHd kinase (EC 2.7.1.27; ATP: thymidine phosphotransferase) activities, compared with cells incubated without drug. The IC50 of AZT was unchanged when the medium concentration of dThd was increased from 0.1 to 50 microM. Increasing the concentration of dThd to 50 microM also did not affect intracellular pools of [3H]AZTDP and [3H]AZTTP or the degree to which [3H]AZT was incorporated into cellular DNA, but did reduce intracellular [3H]AZTMP by approximately 75%. The degree to which 3'-amino-3' deoxythymidine (AMT) was generated from AZT and incorporated into DNA also was not affected by varying the medium concentration of dThd. However, the amount of [3H]-AMT detected in DNA, < or = 3 pmol/10(6) cells at medium concentrations of [3H]AZT < or = 100 microM, was below that associated with significant cytotoxicity in these cells. These data support the notion that, in this model, AZT cytotoxicity is determined by the relative size of AZTTP pools and its utilization in DNA synthesis. Studies to verify this relationship assessed the effect of alterations in the concentration of dTTP and [3H]AZTTP on [3H]AZT incorporation into newly synthesized DNA in vitro, using DNA polymerases isolated from HCT-8 cells. The results of these studies confirmed that alterations in the concentration of either dTTP or AZTTP to reduce the dTTP/AZTTP ratio resulted in an increase in AZT incorporation into DNA. These findings are discussed in light of their biochemical implications and relevance to ongoing clinical trials. PMID- 7980650 TI - Induction in vitro and complete coding region sequence of cytochrome P4501A1 cDNA from cultured whole rat conceptuses during early organogenesis. AB - Exposures of cultured whole rat conceptuses during organogenesis to 3 methylcholanthrene (MC; 0.025-25 microM), 5,6-benzoflavone (BNF; 5-100 microM) or benz[a]anthracene (BA; 5-100 microM) were effected by placement of each of these "MC-type" inducing agents in the culture medium at the time of explantation on day 9.5 of gestation. Conceptuses were then cultured for 48 hr and evaluated on day 11.5 for increased expression of inducible conceptal cytochrome P450 (P450). The three agents each elicited concentration-dependent increases in 7,8 benzoflavone (ANF)-inhibitable ethoxyresorufin O-deethylase (EROD) activities and increased P4501A1 mRNA as detected by primer-specific reverse transcriptase polymerase chain reaction (RT-PCR) in cell-free preparations of the treated, cultured conceptuses. At effective inducing concentrations, dysmorphogenic or other embryotoxic effects were not detectable. At 20 microM concentrations, the three agents exhibited roughly equal induction that was approximately equivalent in magnitude (6- to 13-fold) to that achieved previously with exposures to MC in utero. Additions to the culture medium of 2.5 to 10 microM concentrations of dexamethasone (DEX) did not alter significantly the magnitude of MC-elicited induction in vitro. Repeated full-length sequencing of an RT-PCR-amplified cDNA revealed a coding region sequence identical to that reported for the P4501A1 sequence from adult rat liver. The results provide a basis for investigations, in the absence of maternal influences, of the regulation of mammalian conceptal P4501A1 in intact tissues during organogenesis, a gestational period critical in terms of the dysmorphogenic and other embryotoxic effects of foreign organic chemicals. The results are also pertinent to studies of embryotoxicity, particularly to the transplacental carcinogenicity, mutagenicity and dysmorphogenicity of P4501A1 substrates. PMID- 7980651 TI - Biphasic regulation of cytochrome P450 2B1/2 mRNA expression by dexamethasone in primary cultures of adult rat hepatocytes maintained on matrigel. AB - We have demonstrated recently that although rat hepatocytes rapidly lose their cytochrome P450 mRNA content following their introduction into primary culture, hepatocytes cultured on Matrigel, a reconstituted basement membrane, subsequently spontaneously "reexpress" the mRNAs of some constitutive P450 forms (Kocarek et al., Mol Pharmacol 43: 328-334, 1993). In the present study, we used the Matrigel cell culture system to examine the dose-dependent effects of dexamethasone (DEX) treatments on the mRNAs for two of the P450 forms that are reexpressed spontaneously between days 3 and 5 in culture, 2B1/2 and 2C6. Treatment of cultured hepatocytes with low doses of DEX (10(-9) to 10(-8) M) that induced the mRNA for tyrosine aminotransferase, a model glucocorticoid-inducible gene, suppressed the spontaneous appearance of 2B1/2 mRNA while having little or no effect on the level of 2C6 mRNA or on beta-actin mRNA. However, treatment of the hepatocyte cultures with high doses of DEX (10(-6) to 10(-5) M) that induced P450 3A1 mRNA increased the amounts of the 2B1/2 and 2C6 mRNAs (4.1- and 2.4-fold, respectively, at 10(-5) M DEX). In contrast to the suppressive effects on the spontaneous increases in 2B1/2 mRNA, low doses of DEX (10(-8) to 10(-7) M) enhanced the induction of 2B1/2 mRNA by phenobarbital (2.5-fold at 10(-7) M DEX). Treatment of the hepatocyte cultures with triamcinolone acetonide, another potent glucocorticoid, suppressed spontaneous 2B1/2 mRNA expression at low doses, but did not induce 2B1/2 mRNA at high doses. Treatments with steroids of other classes, including dihydrotestosterone, 17 alpha-ethinylestradiol, fludrocortisone or R-5020, failed to suppress 2B1/2 mRNA levels at low doses. Additionally, treatment with RU-486, a glucocorticoid/progestin receptor antagonist, induced 2B1/2 mRNA at high doses (10(-6) to 10(-5) M). The suppressive effects of DEX on spontaneous 2B1/2 mRNA expression observed at low doses are consistent with a classical glucocorticoid-mediated mechanism, while the high-dose inductive effects of DEX appear to be exerted through a nonclassical mechanism, perhaps akin to that for induction of 3A1. PMID- 7980652 TI - Characterization of cytochrome P450 2E1 induction in a rat hepatoma FGC-4 cell model by ethanol. AB - The hepatic microsomal ethanol-oxidizing system (MEOS) has been well characterized as an important pathway in ethanol metabolism. Cytochrome P450 2E1 (CYP 2E1), the principal component of MEOS, is ethanol inducible and has been implicated in hepatotoxicity associated with alcohol abuse and exposure to organic solvents. Results of chronic in vivo experiments have shown that ethanol induction of hepatic CYP 2E1 occurs by a two-step mechanism. The first step of induction is associated with low blood alcohol concentrations (BACs) and appears to be post-transcriptional, whereas high BACs observed in step-two induction are associated with increased CYP 2E1 gene transcription. The mechanisms underlying these induction steps are under intense investigation. Progress in this area has been limited due to lack of hepatic cell culture models that express CYP 2E1. We report here an in vitro tissue culture cell model, the FGC-4 hepatoma cell line, that exhibits basal levels of CYP 2E1 apoprotein that are inducible by ethanol treatment. Total cellular RNA and microsomal fractions were isolated from control or ethanol-treated confluent cells, and CYP 2E1 mRNA and apoprotein levels were characterized by northern blot or immunoblot analysis, respectively. Initial experiments on isolated microsomes revealed detectable levels of CYP 2E1 apoprotein in control cells that were induced 5-fold in cells treated with 100 mM ethanol for 24 hr. Concentration-response experiments demonstrated that the maximal 24-hr induction in CYP 2E1 apoprotein level was 5-fold and was attained at a concentration of 10 mM ethanol. Interestingly, while the steady-state mRNA levels encoding CYP 2E1 were detectable, they remained unchanged in identically treated cells. Furthermore, there was no observed increase in CYP 2E1 mRNA levels in an extended time course to 72 hr or at higher alcohol concentrations (up to 1500 mM), providing preliminary evidence that the induction is post transcriptional. The time course of CYP 2E1 apoprotein induction by exposure to 100 mM ethanol demonstrated maximal induction at 8 hr. Measurement of CYP 2E1 apoprotein levels after removal of ethanol from pretreated cells demonstrated the half-life of the apoprotein to be 12.7 hr, in good agreement with previous reports using primary hepatocytes. The half-life of the induced protein after ethanol removal in the presence of cyclohexamide (10 micrograms/mL) was biphasic with a rapid 1.8 hr first phase followed by a slower 44.7 hr second phase.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 7980653 TI - Inactivation of hamster monomorphic N-acetyltransferase by vinyl fluorenyl ketone. AB - Arylamine N-acetyltransferases (NATs) are cytosolic enzymes that play important roles in the detoxification and activation of xenobiotic arylamines and their metabolites. Vinyl fluorenyl ketone (VFK) is a selective and potent active site directed irreversible inhibitor of rat liver monomorphic NAT. The present study demonstrated that VFK is an active site-directed affinity label for hamster liver monomorphic NAT, but is a much less effective inactivator of the polymorphic N acetyltransferase isozyme. The potency, irreversibility and selectivity of VFK make it a potentially valuable tool for characterization of NATs that exhibit acetyl donor specificity similar to that of hamster monomorphic NAT. PMID- 7980655 TI - Time course of phorbol-12-myristate-13-acetate (PMA)-induced down-regulation of topoisomerase II in human leukemia cells. AB - The time course of the down-regulation of topoisomerase II associated with phorbol-induced differentiation was quantified in two human HL-60 leukemia cell lines. In the line sensitive to phorbol-induced differentiation (S cells), immunoreactive topoisomerase II levels did not begin to fall until 12 hr following exposure of the cells to phorbol ester. Thereafter, levels declined over the next 36 hr. By contrast, phorbol treatment of the phorbol ester tolerant cell line (PET cells) produced a transient decrease in topoisomerase II only to be followed by a recovery to pretreatment levels. The patterns of the alterations in topoisomerase II mRNA levels mirrored those of the alterations in immunoreactive topoisomerase II. Unexpectedly, nuclear run-on studies revealed that transcriptional start sites were not reduced in either cell line following their exposure to phorbol esters. These data suggest that the down-regulation of topoisomerase II is a consequence rather than a cause of phorbol-induced differentiation in HL-60 cells. Furthermore, this down-regulation is not mediated by a decrease in the number of topoisomerase II transcription sites. PMID- 7980654 TI - Polyol and water accumulation in muscle of galactose-fed rats. AB - Skeletal muscle contains high levels of aldose reductase that catalyzes the reduction of galactose to the polyol galactitol. Galactitol and water were measured in muscle of rats fed a high galactose diet with or without addition of the aldose reductase inhibitor sorbinil. Galactitol, measured in isolated samples of muscle by HPLC, reached steady-state levels (5.9 +/- 1.0 mg/g tissue) within 3 days. Muscle water, determined in vivo by magnetic resonance imaging, increased (51 +/- 5%, P < 0.02) to steady-state levels within 7 days. Both the increased galactitol and water remained constant for the 4-month duration of this study. Aldose reductase activity also remained constant. Sorbinil prevented both the increase in galactitol and the increase in water. These results suggest that the increase in water is due to the osmotic effects of galactitol accumulation and demonstrate that galactitol and water accumulation neither up-regulate nor down regulate aldose reductase expression in skeletal muscle. PMID- 7980656 TI - Simplification of the Wertheimer-Leeper wire code. AB - Wire codes, introduced by Wertheimer and Leeper as a surrogate for residential magnetic fields, divide imputed exposure into several categories based on the configurations of electrical wiring within 40 m of homes. Using the data set gathered by Savitz et al. in the Denver, Colorado, area of the United States, we determined which of the wiring attributes that contribute to Wertheimer-Leeper coding are actually associated with low-power magnetic fields measured in bedrooms of subjects. The results led us to propose a considerably simplified three-category form of the Wertheimer-Leeper code that 1) drops the distinctions between thick and thin primary wires and between first-span and other secondary lines, 2) adds a new distinction between open (i.e., conductors not in physical contact) and spun secondaries, and 3) explains as much of the between-home variability in log-transformed bedroom fields as does the five categories of the original Wertheimer-Leeper code. The data necessary to classify residences using the modified code are considerably simpler to obtain and should lead to more reliable results. A separate reanalysis of the Denver data set of Savitz et al, shows that the modified code yields risk estimates that are both precise and markedly elevated for the highest exposure category, suggesting that this code may be useful in other studies. PMID- 7980657 TI - Sinusoidal 60 Hz electromagnetic fields failed to induce changes in protein synthesis in Escherichia coli. AB - Escherichia coli JM83 [F- ara delta(lac-proAB) rpsL [phi 80d delta (lacZ)M15]] in midlog growth phase at 30 degrees C were exposed to 60 Hz sinusoidal magnetic field of 3 mT of nonuniform diverging flux, inducing a nonuniform electric field with a maximum intensity of 32 microV/cm using an inductor coil. Exposed and unexposed control cells were maintained at 30.8 +/- 0.1 degrees C and 30.5 +/- 0.1 degrees C, respectively. Quadruplicate samples of exposed and unexposed E. coli cells were simultaneously radiolabeled with 35S-L-methionine at 10 min intervals over 2 hr. Radiochemical incorporation into proteins was analyzed via liquid scintillation counting and by denaturing 12.5% polyacrylamide gel electrophoresis. The results showed that E. coli exposed to a 60 Hz magnetic field of 3 mT exhibited no qualitative or quantitative changes in protein synthesis compared to unexposed cells. Thus small prokaryotic cells (less than 2 microns x 0.5 micron) under constant-temperature conditions do not alter their protein synthesis following exposure to 60 Hz magnetic fields at levels at 3 mT. PMID- 7980658 TI - Chromosomal aberrations in human amniotic cells after intermittent exposure to fifty hertz magnetic fields. AB - Our recent studies have shown a significant increase in the frequency of chromosomal aberrations in human amniotic cells after exposure to a sinusoidal 50 Hz, 30 microT (rms) magnetic field. To evaluate further interactions between chromosomes and electromagnetic fields, we have analyzed the effects of intermittent exposure. Amniotic cells were exposed for 72 h to a 50 Hz, 30 microT (rms) magnetic field in a 15 s on and 15 s off fashion. Eight experiments with cells from different fetuses were performed. The results show a 4% mean frequency of aberrations among exposed cells compared to 2% in sham-exposed cells. The difference is statistically significant, with P < 0.05 both excluding and including gaps. In another series of eight experiments, the cells were exposed in the same way but with the field on for 2 s and off for 20 s. Also in these experiments a similar increase in the frequency of chromosomal aberrations was seen, but only when the analysis included gaps. Continuous exposure for 72 h to 300 microT, 50 Hz, did not increase the frequency of chromosomal aberrations. The background electromagnetic fields at different locations within the two incubators used was carefully checked and was nowhere found to exceed 120 nT. Likewise, the background level of chromosomal aberrations in cells cultured at different locations in the incubators showed no significant interculture differences. PMID- 7980659 TI - Effect of microwave radiation on the permeability of carbonic anhydrase loaded unilamellar liposomes. AB - The influence of 2.45 GHz microwave exposure (6 mW/g) on the diffusion processes in enzyme-loaded unilamellar liposomes as bioreactors was studied. The enzyme carbonic anhydrase (CA) was entrapped into cationic unilamellar vesicles. Previous kinetic experiments showed a very low self-diffusion rate of the substrate p-nitrophenyl acetate (PNPA) across intact liposome bilayer. A twofold increase in the diffusion rate of PNPA through the lipid bilayer was observed after 120 min of microwave radiation compared to temperature control samples. The microwave effect was time dependent. The enzyme activity, as a function of increased diffusion of PNPA, rises over 120 min from 22.3% to 80%. The increase in stearylamine concentration reduces the enzyme activity from 80% to 65% at 120 min. No enzyme leakage was observed. PMID- 7980660 TI - Synthesis of diazoluminomelanin (DALM) in HL-60 cells for possible use as a cellular-level microwave dosimeter. AB - Chemical and bacterial synthesis of a thermochemiluminescent polymer known as diazoluminomelanin (DALM) has been previously reported. This paper focuses on the intracellular synthesis of aminomelanin (AM) in mammalian cell lines and subsequent DALM synthesis from this core molecule. B16 melanoma cells, HL-60 myeloid leukemia cells, and RAW 264.7 macrophages show AM and DALM production. Macroscopic image analysis of HL-60 cell lysates containing DALM using the Quantitative Luminescence Imaging System (QLIS) showed increased chemiluminescence (CL) with increased microwave power input and increased temperature. This work represents a first step toward the goal of microscopic radiofrequency dosimetry of individual DALM-loaded cells using image analysis. PMID- 7980661 TI - Exposure of simian virus-40-transformed human cells to magnetic fields results in increased levels of T-antigen mRNA and protein. AB - In its integrated form. SV-40 DNA offers an opportunity to observe the behavior of what is in effect a viral genome within a cellular genome, with transcriptional and translational products that can be clearly distinguished from those of the host cell. Exposure of SV40-transformed human fibroblasts to a 60 Hz continuous-wave sinusoidal electromagnetic (EM) field resulted in increased levels of virally derived mRNA and protein of large T-antigen. These findings provide evidence that a foreign DNA integrated into cells can be affected by EM fields under conditions known to cause increased transcripts from endogenous cellular genes. PMID- 7980662 TI - Development and evaluation of a location-specific wire code. AB - The development of a wire code protocol based on a study of electrical installations in Melbourne, Australia, is described. Because of very significant differences between the Melbourne power distribution system and that used in Denver, Colorado, an approach different from that used by Wertheimer and Leeper was required. A combined practical and theoretical approach was used to determine a continuous exposure index, defined as a measure of the potential for exposure due to external electrical installations. The protocol was tested on a convenient sample of 41 homes in which the field was monitored over a 12 hour overnight period. A correlation of 0.85 (95% CI 0.74-0.92, P < .0001) was obtained between the measured time-weighted average and the wire coding exposure index. To assess the efficacy of the wiring configuration index, a computer simulation of a case control study was then performed. It was concluded that, using the same basic reasoning of the Wertheimer and Leeper code, it is possible to develop a location specific code that provides a good correlation with the residential time-weighted average and an acceptable degree of exposure misclassification. PMID- 7980663 TI - Effects of prenatal exposure to 50 Hz magnetic fields on development in mice: I. Implantation rate and fetal development. AB - Pregnant CD1 mice were exposed or sham-exposed from day 0 to day 17 of gestation to a 50 Hz sinusoidal magnetic field at 20 mT (rms). Preimplantation and postimplantation survival were assessed and fetuses examined for the presence of gross external, internal, and skeletal abnormalities. There were no statistically significant field-dependent effects on preimplantation or postimplantation survival, sex ratio, or the incidence of fetuses with internal or skeletal abnormalities. Magnetic field exposure was, however, associated with longer and heavier fetuses at term, with fewer external abnormalities. The results lend no support to suggestions of increased rates of spontaneous abortion or congenital malformation following prenatal exposure to power frequency magnetic fields. PMID- 7980664 TI - Effects of prenatal exposure to 50 Hz magnetic fields on development in mice: II. Postnatal development and behavior. AB - To investigate the potential of magnetic fields to act as a behavioral teratogen, pregnant CD1 mice were exposed or sham-exposed for all of gestation to a 50 Hz/20 mT magnetic field. Maturation of offspring was assessed using a range of standard developmental indices (eye opening, pinna detachment, hair coat, tooth eruption, sexual maturity, and weight) and simple reflexive behaviors (air righting, surface righting, forepaw grasp, cliff avoidance, and negative geotaxis). Activity and coordination levels were explored in juvenile and adult mice using an open field arena, a head-dip board, an accelerating Rotarod, and a residential activity wheel. All assessments were carried out without knowledge of exposure condition. Results from 168 sham-exposed mice from 21 litters and from 184 exposed mice from 23 litters were compared using survival analysis techniques and multivariate regression methods. Three possible field-dependent effects were found: Exposed animals performed the air righting reflex earlier (P < 0.01); exposed males (but not females) were significantly lighter in weight (P = 0.008) at 30 days of age; and exposed animals remained on a Rota-rod for less time as juveniles (P = 0.03). Some of these results have not been reported in other studies and may reflect spurious statistical significance, although some effect of magnetic field exposure cannot be ruled out. Overall, these results suggest that prenatal exposure to a 50 Hz magnetic field does not engender any gross impairments in the postnatal development or behavior of mice. This does not preclude such exposure affecting more subtle aspects of behavior. PMID- 7980665 TI - Thought barriers to understanding rheumatic diseases. PMID- 7980666 TI - Why a rheumatologist should be interested in arthroscopy. PMID- 7980667 TI - A tribute to leadership: Lawrence E. Shulman, MD, PhD, and the National Institute of Arthritis and Musculoskeletal and Skin Diseases. PMID- 7980668 TI - Effects of local heat and cold treatment on surface and articular temperature of arthritic knees. AB - OBJECTIVE: To evaluate and compare the effects of locally applied heat and cold treatments on skin and intraarticular temperature in patients with arthritis. METHODS: Thirty-nine patients with arthritis of the knee were divided at random into 4 treatment groups (ice chips, nitrogen cold air, ligno-paraffin, and placebo short wave). A temperature probe was inserted into the knee joint cavity and another placed on the overlying skin, and changes in temperature over 3 hours were recorded for each treatment group. RESULTS: The mean temperature of the surface of the skin dropped from 32.2 degrees C to 16.0 degrees C after application of ice chips and from 32.6 degrees C to 9.8 degrees C after application of nitrogen cold air; the mean intraarticular temperature decreased from 35.5 degrees C to 29.1 degrees C and from 35.8 degrees C to 32.5 degrees C, respectively, after these treatments. Treatment with ligno-paraffin increased the surface temperature by 7.5 degrees C and the temperature in the joint cavity by 1.7 degrees C. No significant changes were observed with placebo short wave diathermy. CONCLUSION: The traditional model, that intraarticular temperature is decreased by superficial heat and increased by superficial cold, must be discarded. In arthritis patients, intraarticular temperature is increased by superficial heat and decreased by superficial cold. This has clear consequences for treatment policy. PMID- 7980669 TI - Hypothalamic-pituitary-adrenal axis perturbations in patients with fibromyalgia. AB - OBJECTIVE: To examine basal and stimulated hypothalamic-pituitary-adrenal (HPA) axis and related hormone levels, including adrenocorticotropin (ACTH), cortisol, arginine vasopressin (AVP), and neuropeptide Y (NPY), in patients with fibromyalgia (FM). METHODS: Basal and ovine corticotropin-releasing hormone (oCRH)-stimulated HPA axis function were assessed in 12 patients with FM and in age- and sex-matched normal subjects. Basal plasma AVP levels and AVP release after postural change were assessed, and plasma NPY levels were measured in the same samples. RESULTS: Patients with FM had low 24-hour urinary free cortisol, but normal peak and elevated trough plasma cortisol levels, compared with normal subjects. The net integrated ACTH response to oCRH in FM was not significantly different from that in normal subjects, but tended toward an exaggerated response. There was a significant decrease in net integrated cortisol response to oCRH in FM patients, indicating adrenal hyporesponsiveness. AVP levels were not significantly different between FM patients and control subjects, but variability was greater among the FM patients. Plasma NPY levels were significantly lower in FM patients than in normal subjects. CONCLUSION: These data support the view that HPA axis function is perturbed in patients with FM. Further study is required to ascertain the cause of HPA axis perturbations and their relationship to symptoms in patients with FM. PMID- 7980670 TI - Use of magnetic resonance imaging in diagnosing eosinophilic fasciitis. Report of two cases. AB - OBJECTIVE: To determine the role of magnetic resonance imaging (MRI) in the diagnosis of eosinophilic fasciitis (EF), selection of appropriate biopsy site, and followup of treatment. METHODS: MRI was used to examine 2 patients with EF at the time of their initial clinical presentation and after several months of treatment. T2-weighted axial, T2-weighted axial with fat saturation, and T1 weighted axial post-gadolinium with fat saturation scans at 1.5T were obtained. RESULTS: MRI demonstrated hyperintensity within the fascia. This defect resolved with treatment and clinical improvement. CONCLUSION: MRI is a useful noninvasive tool for diagnosing EF and for monitoring the effectiveness of therapy. PMID- 7980671 TI - Magnetic resonance imaging in systemic lupus erythematosus patients without a history of neuropsychiatric lupus erythematosus. AB - OBJECTIVE: To determine the prevalence of magnetic resonance imaging (MRI) lesions in systemic lupus erythematosus (SLE) patients without a history of neuropsychiatric symptoms and to correlate any MRI abnormalities with the patient's other disease manifestations or treatment. METHODS: Prospective study of 32 consecutive patients with SLE without a history of neuropsychiatric symptoms, from inpatient and outpatient rheumatology services, who underwent MRI scan during a 3-year period. RESULTS: Five patients had MRI abnormalities consisting of white matter lesions or periventricular hyperintensities; this is similar to the prevalence of these abnormalities in the general population. CONCLUSION: The prevalence of silent brain MRI abnormalities is not increased in SLE patients who do not have a history of neuropsychiatric manifestations. PMID- 7980672 TI - Systemic lupus erythematosus induced by ovulation induction treatment. AB - Infertile women are treated with various regimens for ovulation induction. The ultimate end-result of these treatments is a significant rise in levels of serum gonadotropins and estradiol--the most potent natural estrogen. Estrogens may affect diverse biologic functions, including immune and inflammatory reactions. A role for estrogens in the development or exacerbation of systemic lupus erythematosus (SLE) has been suggested by many studies. In this report, we present 3 cases of otherwise healthy women who received ovulation induction agents and subsequently developed full-blown SLE. The possible association between this treatment and SLE is discussed. PMID- 7980673 TI - Occult subacute thyroiditis mimicking classic giant cell arteritis. AB - We report the case of a 60-year-old man who presented with fever, weight loss, generalized aching, left temporal and ear pain, and an erythrocyte sedimentation rate of 125 mm/hour. Due to the presumed diagnosis of giant cell arteritis (GCA), the patient was treated with prednisone (60 mg daily), with immediate improvement in his symptoms. Biopsy of the temporal arteries revealed no significant inflammatory infiltrate. Further evaluation included assessments of thyroid function, which revealed an elevated T4 level, low thyroid-stimulating hormone level, and suppressed radioactive iodine uptake on thyroid scintigraphy. A diagnosis of subacute thyroiditis was made, prednisone therapy was tapered over 3 weeks, and treatment with beta blockers was instituted. The patient remained asymptomatic and returned to a euthyroid state. This case illustrates that subacute thyroiditis should be considered in the differential diagnosis of GCA. PMID- 7980674 TI - Primary systemic amyloidosis presenting as giant cell arteritis and polymyalgia rheumatica. AB - Primary systemic amyloidosis may present with features suggesting a vasculitis, including giant cell arteritis (GCA) and polymyalgia rheumatica (PMR). In this report, we describe the clinical characteristics, temporal artery biopsy findings, and the response of vascular and musculoskeletal symptoms to corticosteroid therapy in 4 patients with primary systemic amyloidosis who presented with manifestations of GCA or PMR. PMID- 7980675 TI - Increased usage of V beta 2 and V beta 6 in rheumatoid synovial fluid T cells. AB - OBJECTIVE: To determine if the T cell antigen receptor V beta usage of unstimulated rheumatoid arthritis (RA) synovial fluid (SF) T cells is biased compared with those in peripheral blood (PB). METHODS: Freshly isolated, matched synovial fluid and peripheral blood T cells were analyzed for V beta gene expression using quantitative polymerase chain reaction (PCR) methods. Ten synovial fluid samples from the knees of 7 patients with RA were studied. The PCR assay used 26 V beta primers with a constant region C beta primer, and 2 C alpha primers that co-amplified a product that served as an internal standard. Cycle number and complementary DNA content were controlled to ensure the linear accumulation of PCR products. Labeled products were separated on 10% polyacrylamide gels and counted with a Betascope blot analyzer. RESULTS: There were consistent differences between the V beta gene usage of SF and PB T cells directly isolated from patients with RA, regardless of HLA-DR haplotype. In all synovial specimens, V beta 2 was increased relative to the peripheral blood, while V beta 13.1 and V beta 13.2 were decreased. V beta 6 and V beta 21 were increased in 9 of the 10 synovial samples. Analyses of bilateral SF specimens from 2 subjects and serial specimens from the same knee of 1 subject revealed virtually identical patterns in each patient. The SF V beta bias was not solely due to differences in the proportion of CD4+ and CD8+ cells, because the CD4:CD8 ratios in SF and PB were similar. However, V beta gene usage of separated CD4+ and CD8+ synovial T cells showed that V beta 2 and V beta 6 were more highly expressed on CD4 cells. CONCLUSION: Freshly isolated synovial T cells from inflamed (not end-stage) knees of patients with RA have a remarkably consistent biased V beta gene usage compared with PB T cells. V beta 2 and V beta 6 are uniformly increased, and this increase is primarily in CD4+ T cells. The same V beta bias in the SF T cells of several RA patients suggests that shared antigens may be stimulating the T cell response. PMID- 7980676 TI - In vivo production of interleukin-10 by non-T cells in rheumatoid arthritis, Sjogren's syndrome, and systemic lupus erythematosus. A potential mechanism of B lymphocyte hyperactivity and autoimmunity. AB - OBJECTIVE: Interleukin-10 (IL-10) is a potent stimulator of B lymphocytes in vitro. In vivo dysregulation of IL-10 gene expression was therefore analyzed in patients with rheumatoid arthritis (RA), primary Sjogren's syndrome (SS), and systemic lupus erythematosus (SLE). METHODS: Spontaneous production of IL-10 by peripheral blood mononuclear cells was measured using reverse transcription polymerase chain reaction and enzyme-linked immunosorbent assay in untreated patients with either RA (n = 10), SS (n = 10), or SLE (n = 10), and in 15 normal control subjects. RESULTS: IL-10 production was dramatically higher in RA, SS, and SLE patients than in controls. In each group, both B lymphocytes and monocytes, but not T lymphocytes, produced IL-10. CONCLUSION: IL-10 production is increased in RA, SS, and SLE. It may play a role in B lymphocyte hyperactivity and in the development of autoimmunity. PMID- 7980677 TI - Inhibition of human fibroblast adhesion by cartilage surface proteoglycans. AB - OBJECTIVE: Recent studies from our laboratory have identified the nonaggregating, collagen-binding proteoglycans, fibromodulin (FM) and decorin, and fibronectin (Fn) and albumin, noncovalently bound at the articular surface of cartilage. The present studies were designed to investigate the interactions between these cartilage macromolecules and the underlying collagen matrix and their role as a barrier to cell adhesion in intact articular cartilage. METHODS: Cell adhesion studies were carried out with human skin fibroblasts incubated on the articular surface of bovine cartilage explants and on collagen-coated and/or Fn-coated plastic surfaces. Interactions of collagen and Fn with either FM or decorin were studied by radioimmunoassay of the same surfaces, using specific antibodies. RESULTS: The present studies show that 1) Fn is immunologically detectable at the intact articular surface of cartilage; 2) fibroblast adhesion to Fn is inhibited by cartilage surface extract proteins and by purified FM, but not by purified decorin; 3) FM has binding affinity for Fn; 4) FM interferes with the binding of a monoclonal antibody specific for the cell-binding domain of Fn; and 5) FM and decorin inhibit collagen-dependent fibroblast adhesion. CONCLUSION: These results indicate that the small proteoglycans at the normal articular surface may act as a barrier to cell adhesion. Since protective cartilage surface proteins break down readily after the induction of acute arthritis in experimental animals, and in rheumatoid cartilage specimens, it is postulated that proteolytic degradation of the surface proteoglycans may be responsible for increasing cell adhesion to, and subsequent pannus invasion of, articular cartilage in inflammatory arthritis. PMID- 7980678 TI - Nucleosome-restricted antibodies are detected before anti-dsDNA and/or antihistone antibodies in serum of MRL-Mp lpr/lpr and +/+ mice, and are present in kidney eluates of lupus mice with proteinuria. AB - OBJECTIVE: To compare the humoral response to nucleosomes with the response to their individual components (double-stranded DNA [dsDNA] and histones) and to assess the involvement of antinucleosome antibodies in immune deposits in the kidney of MRL mice. METHODS: We used enzyme-linked immunosorbent assays of sera and kidney eluates for antibody activity against purified nucleosomes, dsDNA, and histones. RESULTS: Antinucleosome antibodies emerged before anti-dsDNA and antihistone antibodies. A fraction of antinucleosome antibodies reacted exclusively with nucleosomes and not with their components, dsDNA and histones. These nucleosome-restricted antibodies were detected in the proteinuric MRL mouse kidney eluate. CONCLUSION: Our findings support the notion that nucleosomes play a major role in the emergence of antinuclear autoantibodies and that antinucleosome antibodies might be involved in the nephritogenic process in murine lupus. PMID- 7980679 TI - Concentration of autoantibodies to native 60-kd Ro/SS-A and denatured 52-kd Ro/SS A in eluates from the heart of a child who died with congenital complete heart block. AB - OBJECTIVE: To determine the serologic specificity of acid eluates from tissues of a child who died with congenital complete heart block (CCHB). METHODS: Tissues were extracted, acid eluted, and the IgG and antibody titers determined on the eluates by enzyme-linked immunosorbent assay. RESULTS: Antibodies to native 60-kd and denatured 52-kd Ro/SS-A were found to be enriched only in the heart eluate, and not in the eluates from brain, kidney, and skin. CONCLUSION: These findings indicate a major role for anti-native 60-kd Ro/SS-A in the immunopathogenesis of CCHB. PMID- 7980680 TI - Deficiency of the beta subunit of the eighth component of complement presenting as arthritis and exanthem. AB - A 13-year-old boy presented with juvenile chronic arthritis of 6 months' duration. Antinuclear antibodies, anti-double-stranded DNA antibodies, and rheumatoid factor were not detected. Western blotting showed a deficiency of the beta subunit of the eighth component of complement. The same deficiency was present in the patient's sister. C8 beta deficiency is usually detected in individuals who survive meningococcal disease. There was no such history in this family. Juvenile chronic arthritis has not previously been described in patients with C8 beta deficiency. PMID- 7980681 TI - Wegener's granulomatosis and parvovirus B19 infection. PMID- 7980682 TI - Worsening of systemic lupus erythematosus-associated thrombocytopenia after administration of gonadotropin-releasing hormone analog. PMID- 7980683 TI - Proximal gout following renal transplantation. PMID- 7980684 TI - Cyclosporin A in the treatment of systemic lupus erythematosus: comment on the article by Tokuda et al. PMID- 7980685 TI - Limitations in the usefulness of the 28-joint count: comment on the article by Fuchs and Pincus and the editorial by the American College of Rheumatology. PMID- 7980686 TI - Cost-effectiveness of orally administered liquid methotrexate: comment on the letters by McLaughlin and by Wase. PMID- 7980687 TI - Health care reform: how will it affect you? PMID- 7980688 TI - Ethics education for speech-language pathologists and audiologists. PMID- 7980689 TI - Effects of albumin on lipid synthesis, apo B-100 secretion, and LDL catabolism in HepG2 cells. AB - This study examines the effects of extracellular albumin on hepatic apo B-100 metabolism. To do so, a transformed human liver cell line, HepG2, was used as a hepatocyte model and the concentration of albumin in the medium was varied between 0 and 5 g%. Apo B-100 and apo A1 concentrations in the medium were determined by specific enzyme-linked immunoassay (ELISA) and intracellular synthesis of cholesterol ester and triglyceride were determined by addition of appropriate radiolabels to the medium. The data demonstrate that the reduction of extracellular albumin concentration resulted in increased apo B-100 concentration in the medium. Apo A1 secretion, however, was unaffected. While the differences in apo B-100 concentration in the medium were statistically significant (33% +/- 7%, P < 0.0025, 0 g% albumin compared to 5 g% albumin in the medium), the absolute magnitude of the effect under these conditions was relatively modest. Nevertheless, the changes were consistent and evident over incubation periods as long as 8 days. Of interest, although triglyceride synthesis was unaffected, cholesterol ester synthesis changed such that as albumin concentration decreased, synthesis of cholesterol ester increased paralleling the changes in apo B-100 (170% +/- 9%, P < 0.005). These findings were extended by studying interventions which altered cholesterol ester synthesis. Addition of the compound 58-035 (5 micrograms/ml, a specific inhibitor of acylcholesterol acyltransferase activity) resulted in substantial inhibition of cholesterol ester synthesis (39% to 66%, P < 0.025 and P < 0.005, respectively) and apo B-100 concentrations in the medium which decreased by 20% to 28%, P < 0.025. Triglyceride synthesis, in contrast, increased significantly by 32% P < 0.025. Therefore, addition of 58-035 confirmed the previous findings of a parallel relation between cholesterol ester synthesis and apo B-100 concentration in the medium. Nonetheless, albumin still had an additional inhibitory effect on cholesterol ester and apo B-100 secretion. Of interest, when chylomicron remnants (25 micrograms/ml cholesterol), which cause apo B-100 secretion to increase by more than threefold, were added to the medium, albumin now had a more pronounced absolute effect on apo B-100 secretion with a 48% inhibition observed as albumin was increased from 0 to 5 g% in the medium (P < 0.0125). The effect of extracellular albumin on the low density lipoprotein (LDL) pathway was also examined. No differences in non-specific cell association component were detected.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 7980690 TI - Quantitative morphologic study of intimal thickening at the human carotid bifurcation: I. Axial and circumferential distribution of maximum intimal thickening in asymptomatic, uncomplicated plaques. AB - The spatial distribution of intimal thickening was determined for each of 42 carotid bifurcations removed at autopsy from patients with no clinical or anatomic evidence of cerebrovascular disease. Both right and left specimens were available for six of the individuals. Each bifurcation was removed intact and included a 1.5-2.9-cm length of the common carotid artery and a 1.5-2.5-cm length of the internal carotid artery. The specimens were restored to in situ length, fixed under conditions of controlled-pressure perfusion at 100 mmHg, filled with a radio-opaque mixture, radiographed and sectioned at 0.5-cm intervals. Computer assisted contour tracing of projected images of histologic sections was used to determine intimal thickness, intimal cross sectional area and lumen area within each of eight equal 45 degrees polar sectors with 0 degree indexed at the flow divider, 90 degrees at the outside wall, 180 degrees opposite the flow divider and 270 degrees at the inner side wall. Intima occupied 0.9-42% of the area encompassed by the internal elastic lamina, i.e. the potential lumen area if no intimal thickening were present, but there was no lumen narrowing on lateral X ray projections. Intimal thickening was eccentric at each level of section but the circumferential location of maximum intimal thickness (MIT) shifted in a continuous helix from level to level. At the common carotid artery level 1.0 cm proximal to the bifurcation, MIT tended to be at the flow-divider side at 15 +/- 59 degrees. Immediately proximal to the flow divider, MIT was at the lateral side wall. In the mid-sinus region of the internal carotid artery MIT was opposite the flow divider at 179 +/- 64 degrees. At the distal internal carotid just beyond the sinus, MIT was at the inner side wall. The distal internal carotid was minimally involved or free of intimal thickening. Comparison of right and left bifurcations revealed that the helical spatial distribution of MIT was in mirror image symmetry for the two sides. The findings correspond closely with previous demonstrations of a helical flow pattern in the region of the bifurcation. Although locations of MIT just proximal and just distal to the bifurcation are similar and tend to be at the 'far wall', individual differences in the shifts of MIT with axial location should be taken into account when sites of interrogation by non-invasive clinical methods are selected for detection of intimal thickening. PMID- 7980691 TI - Quantitative morphologic study of intimal thickening at the human carotid bifurcation: II. The compensatory enlargement response and the role of the intima in tensile support. AB - Arteries enlarge where intimal plaques form, tending to preserve lumen cross sectional area but causing an increase in mural tangential tension due to the increase in radius. To characterize the compensatory enlargement process at the carotid bifurcation and to evaluate the possible contribution of intima thickening to mural tensile support during the enlarging process, we assessed the relationships among intimal thickening, artery size and estimated tensile stress at 9 sequential axial levels in 42 human carotid bifurcations obtained during post-mortem examinations of 36 adults with no clinical or anatomical evidence of cerebrovascular disease. Right and left bifurcations were available for 6 patients. The arteries were fixed under conditions of controlled pressure distention and histologic sections were prepared at 0.5 cm axial intervals. We determined vessel radius (r), intima thickness (IT), media thickness (MT), intima area (IA), lumen area (LuA) and the area encompassed by the internal elastic lamina (IELA), i.e. the lumen area if there were no intimal thickening. Although IT, IA and r were greatest in the proximal sinus region, there was a highly significant linear relationship between IA and IELA at each axial level; correlation coefficients ranged from 0.64 to 0.97 with P < 0.001 at each level. Stenosis (IA/IELA x 100) ranged from 10.8 +/- 8.0% at the common carotid level immediately proximal to the bifurcation angle to 22.3 +/- 17.9% at the level immediately distal to the angle, but LuA remained nearly constant at each level regardless of IA.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7980692 TI - Human macrophage metabolism of low density lipoprotein oxidized by stimulated neutrophils and ferritin. AB - The metabolism of low density lipoprotein (LDL) oxidized with phorbol myristate acetate (PMA) stimulated neutrophils plus ferritin (LDLox) by human monocyte derived macrophage (HMDM) was studied. Binding of 125I-labeled LDLox to HMDM and further uptake and degradation were higher than for native 125I-labeled LDL. LDLox seems to be taken up by HMDM through the scavenger receptor as indicated by competition studies with unlabeled native and autoxidized LDL. An increased concentration of cellular cholesteryl esters was observed in HMDM exposed to LDLox. Oxidative modification of LDL increased its electrophoretic migration on agarose gel and also the fragmentation of apolipoprotein B. Data suggest that LDLox is incorporated by human macrophages and can potentially induce foam-cell formation. PMID- 7980693 TI - Effect of the acyl-CoA:cholesterol acyltransferase inhibitor, E5324, on experimental atherosclerosis in rabbits. AB - E5324, n-butyl-N'-[2-[3-(5-ethyl-4-phenyl-1H-imidazol-1-yl)propoxy]-6- methylphenyl]urea, a novel and orally absorbable acyl-CoA:cholesterol acyltransferase (ACAT) inhibitor, was evaluated for its antiatherosclerotic and antihyperlipidemic effects in cholesterol-fed hypercholesterolemic rabbits. When administered concurrently with a high-cholesterol (0.5% cholesterol) diet for 12 weeks, E5324 (0.0025%, 0.005% and 0.01% in diet) lowered plasma total cholesterol levels dose-dependently (by about 55%-87% at the end of the experiment compared with the control) and also reduced atherosclerotic plaque formation (about 90% reduction at the highest dose; P < 0.01). In pre-established hypercholesterolemic rabbits, which had been pre-fed a high-cholesterol diet for 8 weeks, E5324 administered in the same diet at a dose of 0.005%, 0.01% or 0.02% for 4 weeks significantly reduced plasma cholesterol levels dose-dependently. Cholesterol content and ACAT activity in the aortic arch were also decreased (by about 72% and 58% at the highest dose, respectively) compared with the control. Another ACAT inhibitor, CI-976, had a similar action, but cholestyramine and probucol (2% and 1% in diet, respectively) lacked anti-atherosclerotic activity in this model. Furthermore, when pre-established hypercholesterolemic rabbits were fed normal rabbit chow diet with or without 0.02% E5324 for 4 weeks, changes in plasma cholesterol levels were similar in both E5324-treated and control groups. On the other hand, E5324 significantly reduced cholesterol content and ACAT activity in the aortic arch (by about 52% and 50%, respectively) compared with the control group. These results indicate that E5324 not only has hypocholesterolemic activity, but also may have a direct effect on the arterial wall in experimental atherosclerosis. PMID- 7980694 TI - Apolipoprotein E2, renal failure and lipid abnormalities in non-insulin-dependent diabetes mellitus. AB - The association of apolipoprotein E (apo E) genetic polymorphism, particularly apo E2, with renal failure (plasma creatinine > or = 1.4 mg/dl, and urinary albumin excretion index > or = 300 mg/g.creatinine and/or persistent proteinuria) was investigated in 57 non-insulin-dependent diabetic (NIDDM) patients. Apo E2 allele frequency was significantly higher in diabetic patients with renal failure (9.6%) than in diabetic patients without renal failure (3.2%) and in the general Japanese population (3.7%). This finding suggests that apo E2 is associated with renal failure in NIDDM. In addition, to elucidate the association of apo E2 with lipid abnormalities, plasma lipid and lipoprotein levels were compared among the apo E2 (E2/2 and E3/2) and E3/3 groups of NIDDM with renal failure (n = 27) and the apo E2 (E3/2) and E3/3 groups of NIDDM with normoalbuminuria (n = 34). In diabetic patients, the apo E2 group with renal failure had significantly higher levels of plasma total cholesterol (T-chol), very-low-density lipoprotein (VLDL) chol, triglyceride (TG), VLDL-TG and apo E than the apo E3/3 group with renal failure, and had significantly higher levels of plasma T-chol, VLDL-chol, TG and VLDL-TG than the apo E2 and E3/3 groups with normoalbuminuria. Furthermore, the apo E2 group with renal failure had significantly higher ratios of VLDL-(chol/TG) and VLDL-chol/TG (an index of remnants in plasma) than the apo E3/3 group with renal failure and the apo E2 and E3/3 groups with normoalbuminuria. These results suggest that apo E2 leads to the accumulation of TG-rich lipoprotein and remnants in plasma. It is concluded that apo E2 is associated with renal insufficiency in NIDDM and that apo E2 may be a factor that aggravates lipid abnormalities in NIDDM with renal failure. PMID- 7980695 TI - Lack of effect of high dose vitamin E on xanthoma regression in homozygous familial hypercholesterolaemia. AB - There is increasing evidence that oxidative modification of low-density lipoprotein (LDL) plays an important role in the pathogenesis of atherosclerosis. Homozygous familial hypercholesterolaemia (HFH) is characterized by premature, severe atherosclerosis. Drugs available at present are ineffective in lowering the markedly elevated LDL levels in this condition; antioxidant therapy to protect the LDL against oxidation may be of benefit. Probucol, the only drug shown to induce xanthoma regression in HFH, is a potent antioxidant, but it also lowers high-density lipoprotein cholesterol (HDL-C) levels, causing some concern. Vitamin E is a naturally occurring antioxidant that does not affect HDL-C levels. We have therefore evaluated the effect of long-term high dose vitamin E on xanthoma regression in HFH. Ten subjects with HFH, mean age 17 years (range 4 34), received vitamin E (400-1000 mg/dl alpha-tocopherol acetate/day) for a period of 23 months (range 12-27). There was a 4.2-fold increase in the mean serum vitamin E level (mean (S.D.) 49.7 (19.9) to 177.9 (45.6) mumol/l; P < 0.005), but no change in serum lipid or lipoprotein concentrations. Although there was an increase in the in vitro resistance of LDL to oxidation as determined by the duration of the lag phase during copper-mediated oxidation (116 (8.34) vs. 141.5 (9.23) min; P < 0.005) there was no xanthoma regression; in fact they progressed in 4 subjects. Unlike probucol, high dose long-term vitamin E has no demonstrable effect on xanthoma regression in HFH. PMID- 7980696 TI - Glycosylation pattern of platelet glycoprotein IIb and IIIa in type IIa hypercholesterolemia. AB - The microheterogeneity and polymorphism of platelet membrane glycoproteins IIb and IIIa from hypercholesterolemic type IIA patients and from normolipidemic controls were compared by isoelectric focusing followed by immunological detection. Their size and the extent of glycosylation were investigated by polyacrylamide gel electrophoresis and carbohydrate affinity stain. No qualitative or quantitative differences could be detected, either within each test group or between the two groups. This finding rules out the hypothesis that altered molecular forms of the glycoproteins forming the fibrinogen receptor might be involved in the pathogenesis of platelet hyperaggregability in hypercholesterolemic patients. PMID- 7980697 TI - Genetic polymorphism of apolipoprotein A-IV in five different regions of Europe. Relations to plasma lipoproteins and to history of myocardial infarction: the EARS study. European Atherosclerosis Research Study. AB - As a part of the EARS study we assessed the role of the common apo A-IV polymorphism in determining the hereditary predisposition to cardiovascular disease. The study population consisted of 1261 controls and 629 cases (students whose father had MI before 55 years) from five different European regions. The apo A-IV 1-1 phenotype accounted for 85% of the individuals. One per cent of subjects were homozygous for the apo A-IV2 allele. There was significant regional variation in the apo A-IV allele frequencies from North to South in Europe, with the lowest A-IV2 frequency in Finland. The distribution of the apo A-IV phenotypes was similar in cases and controls, as was the regional variation. The apo A-IV polymorphism did not affect HDL cholesterol. There was no correlation between apo A-IV alleles and the plasma concentration of apo A-IV. The plasma concentration of apo A-IV was lower in females than in males; furthermore, there was a significant difference in apo A-IV concentrations between oral contraceptive users and nonusers: users had the lowest values. As no strongly significant genetic difference could be demonstrated between plasma lipid concentration in cases and controls, and as the apo A-IV polymorphism did not significantly influence plasma lipid concentration, we conclude that the apo A-IV gene is not a major determinant of the risk for MI and/or CHD. PMID- 7980698 TI - Contribution of visceral fat accumulation to the development of coronary artery disease in non-obese men. AB - Associations between intra-abdominal visceral fat accumulations and coronary risk factors were studied in a sample of 29 non-obese men aged 57 +/- 10 years with coronary artery disease (CAD). Their body mass indexes (BMI) were 23.8 +/- 1.5 (range 18.7-26.3). The visceral fat area (VFA) and the subcutaneous fat area (SFA) were measured at the level of the umbilicus by computed tomography. In patients with CAD, the average VFA was significantly increased compared with that in 54 control subjects without CAD, matched for sex, age, and BMI (117.2 +/- 53.1 vs. 93.8 +/- 38.6 cm2, P < 0.05). However, their average SFA was not statistically different (111.2 +/- 33.3 vs. 106.3 +/- 35.7 cm2, N.S.). Eleven CAD patients (38%) and nine control subjects (17%) had greater than 2 S.D. higher than the mean VFA obtained from 22 healthy subjects extracted from the control subjects. Accordingly, the proportion of the subjects with high VFA was significantly higher in the CAD group. This group also had significantly higher levels of plasma glucose and insulin areas than controls determined by oral glucose tolerance tests. This may be due to insulin resistance. The proportion of the subjects with multiple risk factors including hyperlipidemia, hyperglycemia, and hypertension was significantly higher in the CAD patients with high VFA compared with the control subjects with normal VFA (CAD with high VFA 82% and control with normal VFA 33%). These findings suggest that visceral fat accumulations may play an important role in the occurrence of CAD regardless of obesity.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7980699 TI - The hypocholesterolemic action of TA-7552 and its effects on cholesterol metabolism in the rat. AB - The hypocholesterolemic property of 1-(3,4-dimethoxyphenyl)-2,3- bis(methoxycarbonyl)-4-hydroxy-6,7,8-trimethoxynaphthalene (TA-7552) and its effects on cholesterol metabolism were investigated in the rat. TA-7552 incorporated into a hypercholesterolemic diet at a concentration of 0.2% and administered for 7 days reduced serum cholesterol by 72% and liver cholesterol by 90%, and its minimal effective dose was 0.01% in the diet. Its hypocholesterolemic effect was associated with an elevation of serum HDL cholesterol. Inclusion of 0.1% TA-7552 in the normal laboratory chow accelerated fecal excretion of 14C derived from orally administered 4-[14C]cholesterol or carbonyl-[14C]taurocholate. The net amounts of fecal neutral sterols and bile acids were markedly increased by the same treatment. Hepatic bile acid production and hepatic and intestinal cholesterol biosynthesis as measured by cholesterol 7 alpha-hydroxylase activity and 1-[14C]acetate incorporation into tissue cholesterol, respectively, were both stimulated by the drug treatment. All these data indicate that this hypocholesterolemic agent inhibits intestinal absorption of both cholesterol and bile acids and compensatorily stimulates hepatic production of bile acids and cholesterol. PMID- 7980700 TI - Thrombomodulin and smoking. PMID- 7980701 TI - Thrombomodulin and smoking. PMID- 7980702 TI - The vascular nervous skeleton: a disregarded factor of vascular pathology. AB - The nervous supply of the vascular wall in its organ entirety represents the felt like 'nervous skeleton'. Its growth is more vulnerable than that of any other tissue component of the developing vessel wall. Selective growth impairment of the vascular nervous skeleton should result in developmental vascular stenosis. Escape of the epithelial or smooth muscle cells from the confines of the nervous skeleton should be taken into account as a possible common denominator of carcinogenesis and atherogenesis. PMID- 7980703 TI - Malondialdehyde concentration in plasma is inversely correlated to the proportion of linoleic acid in serum lipoprotein lipids. AB - It has been suggested that the susceptibility of low density lipoprotein (LDL) to oxidative stress depends on the balance between its contents of polyunsaturated fatty acids and antioxidants. In a healthy reference population (n = 103), the plasma concentration of malondialdehyde (MDA) (mean 0.86, range 0.50-1.27 mumol/l) was positively correlated to the serum concentrations of LDL cholesterol (r = 0.31, P = 0.001), very low density lipoprotein triglycerides (r = 0.25, P = 0.009) and apolipoprotein B (r = 0.23, P = 0.03), and negatively correlated to lipid corrected alpha tocopherol in serum (r = -0.22, P = 0.02) and lipoprotein(a) (Lp(a)) (r = -0.26, P = 0.01). Plasma MDA was negatively correlated to the content of linoleic acid in the serum lipoprotein phospholipids (r = -0.35, P = 0.0008). In a stepwise regression analysis 12% of the variation in plasma MDA was explained by variations in the content of linoleic acid and 27% after addition of Lp(a) and abdominal sagittal diameter. The significant negative relation between plasma MDA and the amount of linoleic acid in the lipoprotein lipids indicates that other factors, e.g. the availability of anti-oxidants and the lipoprotein metabolism, may be of greater importance for intravascular lipid peroxidation than the proportion of polyunsaturated fatty acids in the lipoprotein lipids. PMID- 7980704 TI - Conjugated linoleic acid and atherosclerosis in rabbits. AB - Conjugated linoleic acid (CLA) consists of a series of positional and geometric dienoic isomers of linoleic acid that occur naturally in foods. CLA exhibits antioxidant activity in vitro and in vivo. To assess the effect of CLA on atherosclerosis, 12 rabbits were fed a semi-synthetic diet containing 14% fat and 0.1% cholesterol for 22 weeks. For 6 of these rabbits, the diet was augmented with CLA (0.5 g CLA/rabbit per day). Blood samples were taken monthly for lipid analysis. By 12 weeks total and LDL cholesterol and triglycerides were markedly lower in the CLA-fed group. Interestingly, the LDL cholesterol to HDL cholesterol ratio and total cholesterol to HDL cholesterol ratio were significantly reduced in CLA-fed rabbits. Examination of the aortas of CLA-fed rabbits showed less atherosclerosis. PMID- 7980705 TI - Discrimination between RRR- and all-racemic-alpha-tocopherols labeled with deuterium by patients with abetalipoproteinemia. AB - The ability to discriminate between stereoisomers of alpha-tocopherol was studied in five patients with abetalipoproteinemia (ABL) because an impairment in secretion of apolipoprotein B-containing lipoproteins might impede the normally enhanced plasma transport of RRR-alpha-tocopherol. An oral dose containing 3.7 g of each 2R, 4'R,8'R-alpha-[5-C2H3]tocopheryl acetate (d3RRR-alpha-tocopheryl acetate) and 2RS,4'RS,8'RS-alpha-[5,7-(C2H3)2]tocopheryl acetate (d6 all rac alpha-tocopheryl acetate) was administered, then the labeled and unlabeled alpha tocopherol contents of plasma and red blood cells from multiple blood samples obtained at selected times up to 72 h following the dose were quantitated. ABL plasma contained about 1%-10% of the d3-RRR-alpha-tocopherol concentrations of normal subjects given only 150 mg of each isotope. Three of the patients discriminated between forms of alpha-tocopherol with ratios of RRR-/allrac-alpha tocopherol > or = 1.8, similar to normals. These data suggest that the hepatic tocopherol binding protein is present and functional in ABL patients. Although two of the patients did not discriminate between stereoisomers of alpha tocopherol, it is likely that this resulted from nearly a complete block in very low density lipoprotein (VLDL) secretion. Thus, the ability of ABL patients to absorb and transport orally administered vitamin E is markedly impaired and variable among patients. PMID- 7980706 TI - Relationships between risk factors and morphological patterns of human carotid atherosclerotic plaques. A multivariate discriminant analysis. AB - The histological characterization of the fibroatheromatous plaques and their histogenesis are still to be defined. Factors responsible for the evolution of intimal components and the mechanisms and stages of fibroatheromatous plaque formation are still largely obscure. Focusing on symptomatic plaques, the aim of this study is to determine whether plaque heterogeneity is the result of a haphazard clustering of various components or an organized pattern in response to risk factors. To this end, 180 carotid plaques from patients affected by transient ischemic attacks (TIA) or by stroke, with angiographic stenosis greater than 50%, were studied after endoarterectomy. Clinical and morphological data were collected by means of a pre-defined protocol, quantified and correlated, by using the discriminant analysis, with age, sex, hypertension, diabetes, hypercholesterolemia and smoking habit. Our results show that the relationships between plaque components are non-random and consistent with the knowledge derived from studies on human and experimental plaques. Moreover, some plaque patterns can be significantly correlated with single risk factors. The fibrous plaque was correlated with aging and diabetes; the granulomatous plaque, rich in giant cells, with the female sex and hypertension; the xanthomatous plaque, rich in foam cells and with extensive alcianophilia, with hypercholesterolemia. In the smokers, finally, the plaques were frequently complicated by mural thrombosis. PMID- 7980707 TI - Transendothelial transport of modified low-density lipoproteins. AB - Human umbilical vein endothelial cell monolayers were grown as monolayers on porous filters and their transcellular transport and degradation of 125I-labelled native and modified forms of LDL, supplied to either the intimal or the luminal face, were measured. Intact native, acetylated and oxidized LDL were all transported in both directions across the cell monolayers by receptor-independent mechanisms, and all forms of LDL were transported at similar rates. However, the mass of intact LDL transported from the intimal to the luminal face of the monolayer was always fourfold more than that transported in the opposite direction under similar conditions. In addition to LDL transport, endothelial cell monolayers also degraded native and modified forms of LDL by predominantly receptor-dependent routes, in that these could be inhibited (> 70%) by the addition of a 20-fold excess of the same form of (but unlabelled) LDL. The measured amounts of lipoprotein degraded were the same whether supplied to the intimal or the luminal face. Incubation of endothelial cells with oxidized LDL led to intracellular accumulation of a pool of macromolecular apo B which was apparently resistant to lysosomal proteolysis. PMID- 7980708 TI - Inhibitors of angiotensin converting enzyme decrease early atherosclerosis in hyperlipidemic hamsters. Fosinopril reduces plasma cholesterol and captopril inhibits macrophage-foam cell accumulation independently of blood pressure and plasma lipids. AB - The effect of two angiotensin converting enzyme (ACE) inhibitors on the development of atherosclerosis was determined in hyperlipidemic hamsters. Preliminary studies indicated that only fosinopril (50 mg/kg) temporarily decreased mean arterial pressure, while after chronic dosing fosinopril and captopril (50 mg/kg) were ineffective. The same dose of fosinopril and captopril inhibited the angiotensin I pressor response, indicating these agents suppressed ACE activity in vivo. In the 3 week atherosclerosis experiment, all hamsters were fed chow supplemented with 0.05% cholesterol and 10% coconut oil. Control hamsters were compared with those receiving either 50 mg/kg per day of fosinopril or 50 mg/kg per day of captopril. After 3 weeks, fosinopril reduced plasma total cholesterol, low density lipoprotein (LDL) plus very low density lipoprotein cholesterol and total triglycerides by 17%, 27% and 45%, respectively. Captopril only reduced high density lipoprotein cholesterol by 20%. Neither fosinopril or captopril altered blood pressure at 3 weeks. Atherosclerosis was quantified from en face preparations of the lesion-prone aortic arch that were stained with oil red O (for cholesteryl ester and triglycerides). In control hamsters, oil red O labeled numerous subendothelial macrophage-foam cells located along the inner curvature of the aortic arch. Compared with controls, fosinopril reduced the number of intimal macrophage-foam cells/mm2, foam cell size and the fatty streak area by 85%, 38% and 90%, respectively. Captopril decreased these parameters by 44%, 16% and 53%. Thus captopril decreased early atherosclerosis without affecting plasma LDL cholesterol or blood pressure, which suggested that inhibiting ACE (or kininase II) directly impeded the accumulation and formation of macrophage-foam cells.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7980709 TI - Differential effect of dietary fat saturation and cholesterol on hepatic apolipoprotein gene expression in rats. AB - The effects of dietary cholesterol and fat saturation on hepatic apolipoprotein A I, A-II, A-IV, B, C-I, C-III, E and LDL receptor mRNA levels were studied in male rats. Animals were maintained for 2 months on a high fat diet (40% w/w) containing 0.1% cholesterol. Two groups of control animals received either chow diet or chow plus 0.1% cholesterol, while experimental groups received as their fat supplement coconut, corn or olive oil. Olive oil fed animals had higher levels of hepatic apo A-I than the control cholesterol group (1.6 +/- 0.3 vs. 0.8 +/- 0.2). Apo E mRNA levels were 50% and 72% higher in animals consuming the saturated (coconut) and unsaturated (corn and olive) fat diet than the control cholesterol group. Apo B and apo C-I mRNA levels were not affected by the experimental conditions. Apo A-IV mRNA increased between 66% and 127% in groups in which cholesterol was present. LDL receptor mRNA increased 2 times in the corn fed group compared with the control groups. These results indicate that the expression of genes coding for products involved in lipoprotein metabolism have a differential susceptibility to dietary fat saturation and cholesterol. PMID- 7980710 TI - Relation of N-glycosylation of apolipoprotein B-100 to cellular metabolism of low density lipoprotein. AB - We studied the functional role of N-linked sugar chains of apolipoprotein (apo) B 100 of low density lipoprotein (LDL) in cholesterol metabolism. The N-linked sugar chains of apo B-100 of LDL obtained from four homozygous Watanabe heritable hyperlipidemic (WHHL) rabbits were liberated by hydrazinolysis, followed by NaB3H4 reduction and were fractionated by paper electrophoresis and column chromatography. They consisted of one neutral (N) and two acidic (A1, A2) fractions. The ratio of apo B-100 acidic fractions (A1+A2) varied among 4 WHHL rabbits. Serial measurements of serum cholesterol levels showed that they decreased with aging in each of 4 WHHL rabbits. We investigated the relation of the ratio of acidic sugar chains of apo B-100 to the serum cholesterol levels. Reciprocals of the serum cholesterol levels were significantly correlated with the ratio of acidic sugar chains of apo B-100 (r = 0.901, P < 0.001). To elucidate the role of N-linked sugar chains of apo B-100, we investigated cellular uptake of LDL in normal rabbit skin fibroblasts. The amounts of association, degradation and cholesteryl esterification of LDL with a lower ratio of acidic sugar chains at 37 degrees C were greater than those of LDL with a higher ratio of acidic sugar chains. These results suggest that N-glycosylation of apo B-100 may be related with serum cholesterol levels and N-linked sugar chains of apo B-100 may play an important role in cellular metabolism of LDL. PMID- 7980711 TI - Lp(a) lipoprotein in cardiovascular disease. AB - The article summarizes the increased knowledge about the enigmatic Lp(a) lipoprotein and its clinical importance over the past 20 years. The mode of inheritance, the unique features of Lp(a) composition and structure and the unusual distribution of the mainly genetically determined plasma Lp(a) levels are discussed. The main factors that can significantly change the inherited plasma Lp(a) levels are endocrine disorders and hormone treatment. It seems possible that sex hormones protect females to a large extent from the potentially deleterious effects of inherited high Lp(a) levels until menopause. The exceptionally strong independent association found in most studies between Lp(a) lipoprotein levels and atherosclerotic disorders indicates that Lp(a) is a factor of outstanding importance in the pathogenesis of atherosclerosis. Probable pathogenetic mechanisms are reviewed. The associations found between LP(a) and insulin release, rheumatoid arthritis and renal diseases suggest that Lp(a) may be involved in immunological mechanisms. In a new hypothesis it is suggested that an autoimmune process might especially occur in individuals with inherited high Lp(a) levels and certain HLA class II genotypes, triggered by a concurrent infection. PMID- 7980712 TI - Biomarkers of dietary fat composition in young adults with a parental history of premature coronary heart disease compared with controls. The EARS Study. AB - The European Atherosclerosis Research Study (EARS) is a study of the biological expression of a paternal history of premature coronary heart disease. The study was carried out in 14 centres in 11 European countries, where the offspring of fathers who suffered a documented myocardial infarction before the age of 55 years (cases) were compared with age- and sex-matched controls. In this paper we describe the measurement of plasma cholesteryl esters as biomarkers for the fatty acid composition of the diet in the cases and controls. No significant differences were found. Cholesteryl palmitate, oleate, linoleate and arachidonate were measured in plasma and correlated with plasma lipids and lipoproteins and with life-style variables including body-mass index, alcohol consumption, tobacco and physical activity. The strongest correlations were observed between cholesteryl esters and triglycerides, which are positively correlated with cholesteryl oleate and negatively with cholesteryl linoleate. Apo B was negatively correlated with cholesteryl linoleate and positively with palmitate. Among the other variables, alcohol was positively correlated with cholesteryl oleate and negatively with linoleate, both in males and in females. Furthermore, there are differences between regions, with the highest percentages of saturated cholesteryl palmitate measured in Finnish students, the highest percentage of cholesteryl linoleate in Belgium and of cholesteryl arachidonate in Southern Europe. PMID- 7980713 TI - Effects of ciprofibrate on LDL metabolism in man. AB - This study examined the effects of ciprofibrate therapy (100 mg/day) on plasma lipids, lipoproteins and low density lipoprotein (LDL) kinetic heterogeneity in moderately hypercholesterolaemic subjects. The drug lowered plasma triglyceride and cholesterol by 41% and 17%, respectively. Very low density lipoprotein (VLDL) cholesterol fell by 38%, LDL cholesterol fell by 22%, while the content of the lipid in high density lipoprotein (HDL) increased by 11%. LDL structural and metabolic heterogeneity were assessed before and during therapy in eight subjects. Density gradient centrifugation was used to fractionate LDL into three species. LDL-I, the least dense, was not affected by therapy whereas LDL-II and LDL-III were decreased by 28% (P < 0.01) and 31% (N.S.). Baseline turnover studies revealed that LDL catabolism was subnormal and this was the cause of the raised cholesterol in these subjects. Ciprofibrate therapy increased the apoLDL fractional catabolic rate (FCR) by 19%, principally by inducing a 38% enhancement (P < 0.03) in apoLDL removal by the receptor pathway. ApoLDL kinetics exhibited metabolic heterogeneity both before and during drug therapy. Analysis of plasma decay curves for the LDL tracer and urinary excretion data indicated that the lipoprotein comprised two metabolically distinct species, one with an FCR of about 0.50 pools/day (Pool A), the other with an FCR of about 0.18 pools/day (Pool B). Drug therapy decreased synthesis of and hence reduced the plasma mass of apoLDL in the slow metabolised pool B. This perturbation in synthesis was linked to the change in plasma triglyceride concentration. The resultant reduced proportion of pool B vs. pool A material accounted for the observed promotion of LDL receptor-mediated clearance. Ciprofibrate, therefore, produced beneficial changes in the plasma levels of VLDL, LDL and HDL and in the metabolism of LDL. PMID- 7980714 TI - Decreased plasma levels of lipoprotein(a) in patients with hypertriglyceridemia. AB - Lipoprotein(a) (Lp(a)) is an atherogenic lipoprotein which is similar in structure to, but metabolically distinct from, LDL. Factors modulating plasma Lp(a) concentrations are poorly understood. To investigate the possible interaction of Lp(a) with triglycerides, we determined the apo(a) phenotype, Lp(a) concentration, and distribution of Lp(a) in a group of patients with triglycerides > 400 mg/dl (n = 60) compared with a control group (n = 128). Lp(a) concentrations were significantly lower in hypertriglyceridemic patients (mean +/ S.E., 13 +/- 4 mg/dl; median, 6 mg/dl; 25/75 percentile, 2-13 mg/dl) as compared with the controls (mean, 22 +/- 2 mg/dl; median, 10 mg/dl; 25/75 percentile, 7-30 mg/dl). Plasma Lp(a) concentrations in the hypertriglyceridemic patients correlated negatively with triglyceride levels (r = -0.69, P = 0.03). The difference in Lp(a) levels between patients and controls was maintained when subjects were stratified by apo(a) phenotype and type of hyperlipidemia. After subdividing the hypertriglyceridemic patients into one group with apo(a) isoforms < or = S2 and one group with apo(a) isoforms > or = S3, we found that the differences in plasma Lp(a) concentrations between patients and controls were more pronounced in the group with the lower molecular weight apo(a) isoforms. These data indicate that hypertriglyceridemia is associated with lower plasma Lp(a) concentrations and suggest that increased levels of triglyceride-rich lipoproteins may influence the metabolism of Lp(a). PMID- 7980716 TI - Metabolic effects of alterations in meal frequency in hypercholesterolaemic individuals. AB - It has been suggested that the metabolic consequences of a given diet may depend in part on the frequency with which meals are eaten. To investigate the effects of meal frequency on plasma lipid metabolism, 16 free-living hypercholesterolaemic men and women consumed their usual diet as 3 or 9 meals/day in random order for 4 weeks. Dietary macronutrient intake and body weight remained similar on the 2 regimens. Fasting plasma lipids were measured after 2, 3 and 4 weeks on each regimen and there were no significant differences in the fasting concentrations of plasma total, LDL, and HDL cholesterol, triglycerides, apolipoprotein A-I and B and the ratio of total: LDL and LDL:HDL cholesterol (HDL C) on the two diets. The mean (+/- S.D.) fasting total cholesterol was 6.73 +/- 0.74 and 6.81 +/- 0.88 mmol/l on 3 and 9 meals/day, respectively and LDL-C was 4.77 +/- 0.66 and 4.87 +/- 0.78 mmol/l, respectively. There was also no significant variation in the response of plasma triglycerides or serum insulin to a high fat meal following a 3 week adaptation to regimens of 3 and 9 meals/day. Finally the 24 h urinary output of C-peptide was similar on each diet. The consumption of isoenergetic diets as 3 and 9 meals/day did not influence fasting plasma lipid levels, C-peptide excretion or the plasma triglyceride response to a high fat meal of a group of free living hypercholesterolaemic subjects. PMID- 7980715 TI - Effect of TFC-612, a 7-thia prostaglandin E1 derivative, on intimal thickening after endothelial injury with balloon catheter in rats. AB - The effect of TFC-612, methyl-6-[(1R,2S,3R)-hydroxy-2-](1E,3S,5R)-3- hydroxy-5 methyl-1-nonenyl]-5-oxocyclopentyl)thio] hexanoate, on intimal thickening of carotid artery 14 days after endothelium denudation with a balloon catheter was examined in rats. This compound significantly suppressed the neointimal area and the ratio of intimal and medial layer by 41.1% and 31.4%, respectively, at 3.2 micrograms/rat/h s.c. infusion. At this dose, this compound did not inhibit platelet aggregation induced by either collagen or ADP. It did not inhibit bromodeoxyuridine incorporation into medial smooth muscle cells at 3 days after injury. In in vitro experiments, TFC-612 did not inhibit the [3H]thymidine uptake into cultured smooth muscle cells, but it showed significant inhibition of smooth muscle cell migration induced by platelet-derived growth factor (PDGF) at more than 10(-9) M. This compound increased cyclic AMP levels dose dependently in cultured smooth muscle cells at more than 10(-8) M. These results suggest that TFC-612 inhibits intimal thickening by inhibition of smooth muscle cell migration from media to intima through cyclic AMP elevation. PMID- 7980717 TI - Partial characterization of endothelin-converting enzyme activity in human serum lipoproteins. AB - Endothelin (ET)-1 is an endothelium-derived vasoconstrictor and mitogen peptide generated from an intermediate form (big ET-1) by endothelin-converting enzyme(s) (ECE). In this study, we partially characterized ECE activity in human serum lipoprotein fraction. By gel filtration chromatography, lipoprotein ECE activities consisted of three major components: the first and the second peak eluted in the positions of very low density lipoprotein (VLDL) and low density lipoprotein (LDL), respectively, while the third peak eluted earlier than that of high density lipoprotein (HDL), whose apparent molecular weight (550 kDa) was similar to that of apolipoprotein B (apo B). Both VLDL/LDL-associated and free ECE fractions were similarly inhibited by metalloproteinase and serine proteinase inhibitors. Free ECE fraction was precipitable with dextran sulphate and manganese ion in the same manner as lipoprotein ECE. Apo B purified by high performance liquid chromatography had the same ECE activity as lipoprotein ECE, whose activity was removed after immunoprecipitation with polyclonal anti-apo B antibody. Our data suggest that ECE activity in human serum lipoproteins may be associated with an apo B-like component, although it needs to be characterized completely. PMID- 7980718 TI - Triglyceride-rich lipoproteins of subjects heterozygous for apolipoprotein E2(Lys146-->Gln) are inefficiently converted to cholesterol-rich lipoproteins. AB - The APOE*2(Lys146-->Gln) allele behaves like a dominant trait in the expression of familial dysbetalipoproteinemia (FD) (Smit et al., J. Lipid Res. 1990; 31: 45 53). FD patients carrying the APOE*2(Lys146-->Gln) allele exhibit less elevated cholesterol to triglyceride ratios in the d < 1.019 g/ml lipoprotein density fraction as compared to classical FD patients displaying homozygosity for the APOE*2(Arg158-->Cys) allele (0.8 vs. 1.4). Upon treatment of complete serum with lipoprotein lipase (LPL), the mean cholesterol to triglyceride molar ratio of the d < 1.019 g/ml lipoprotein fraction in these FD patients increased only marginally (from 0.8 to 1.1), as compared with that of classical FD subjects (from 1.4 to 2.6) and non-FD control subjects (from 0.7 to 1.5). In order to obtain further evidence for an inefficient lipolysis of the d < 1.019 g/ml lipoprotein fraction in APOE*2(Lys146-->Gln) carriers, possibly in combination with a less efficient cholesteryl ester transfer protein (CETP) activity, blood samples of APOE*2(Lys146-->Gln) allele carrying FD patients were analysed and compared with classical FD patients and controls. In the APOE*2(Lys149-->Gln) allele carrying FD patients were analysed and compared with classical FD patients and controls. In the APOE*2(Lys146-->Gln) FD patients, the increase in plasma cholesterol was mainly confined to the very low density lipoprotein (VLDL) fraction, whereas in classical FD patients, the levels of cholesterol in the intermediate density lipoprotein (IDL) fraction was also dramatically increased (ratios of VLDL to IDL cholesterol are 4.7 and 2.6, respectively). Family analyses of the APOE*2(Lys146-->Gln) FD subjects showed that the apo E to apo B ratio in the d < 1.019 g/ml lipoprotein fraction of allele carriers is 3.5 times as high as that found in non-carriers (2.8 vs. 0.8, by wt.). Also, in the APOE*2(Lys146-->Gln) allele carrying family members, the ratio of cholesterol to triglyceride of the d < 1.019 g/ml lipoprotein fraction is less markedly elevated upon addition of LPL when compared to that in non-carrying controls (from 1.1 to 1.8 vs 0.7 to 1.6). The efficiency of the d < 1.019 g/ml lipoprotein fraction of APOE*2(Lys146-->Gln) FD patients to compete with low density lipoprotein (LDL) for binding to the LDL receptor is intermediate to that of controls and classical APOE*2(Arg158-->Cys) homozygous FD patients. These findings suggest that in APOE*2(Lys146-->Gln) allele carriers, the conversion of VLDL into IDL is impaired due to an inefficient lipolysis, possibly in combination with a retarded CETP activity.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7980719 TI - Epidemiological evidence for an association between serum calcium and serum lipids. AB - To study the association between serum calcium and serum lipids, data from 5394 men and 4800 women in the Belgian Interuniversity Research on Nutrition and Health (25-74 years) were used. By visual inspection of the data a linear increase of both total and HDL cholesterol with serum calcium levels was observed, consistently over all age groups and both sexes. In order to adjust the measured serum calcium concentrations for total serum protein, statistical analyses were performed using Parfitt's correction formula. Multivariate analysis showed in both sexes a highly significant positive association between corrected calcium and total cholesterol independent of age, systolic blood pressure, body mass index, serum uric acid, P/S ratio of diet, cholesterol intake, smoking, educational level and geographical area. The adjusted differences in total cholesterol between the lowest and highest quartile range of the calcium distribution were about 13 mg/dl for both men and women. Protein-corrected calcium was among the strongest correlates with total cholesterol. The analysis of the relation with HDL cholesterol revealed an effect modification by gender. For men no statistically significant correlation between calcium and HDL cholesterol was observed while for women a strong increase of HDL with protein corrected calcium was found resulting in an adjusted difference of 2.5 mg/dl between the lowest and highest calcium quartile range. PMID- 7980721 TI - Xth International Symposium on Atherosclerosis. Montreal, 9-14 October 1994. Abstracts. PMID- 7980720 TI - Chylomicron retention disease: exclusion of apolipoprotein B gene defects and detection of mRNA editing in an affected family. AB - Chylomicron retention disease (CRD) is a rare autosomal recessive disorder characterized by the absence of post-prandial chylomicrons and apolipoprotein (apo) B-48 in sera from affected individuals. Apo B-100 is synthesized, and apo B 100-containing lipoproteins are present in sera. A crucial difference between the synthesis and secretion of apo B-containing lipoproteins from the liver and gut in man is the generation of apo B-48 by editing of apo B mRNA in the gut to create a premature stop-translation codon. In this study the hypothesis that CRD may represent an absence of editing of apo B mRNA in the gut was investigated. Two affected sisters were identified as having low cholesterol levels and an absence of post-prandial chylomicronemia. Segregation analysis in the family showed that the apo B locus is not the site of the defect. Using reverse transcription-polymerase chain reaction (RT-PCR), duodenal biopsy-mRNA from the affected sisters was isolated and analyzed. The apo B editing site was amplified after cDNA synthesis, and the products analyzed by the primer extension assay. The results show that editing of apo B mRNA is normal in patients with CRD. The data provides strong confirmation that the primary defect in CRD is not in the synthesis, or editing of apo B mRNA in the gut. More likely, the disease arises from a defect in a gene crucial to the assembly and/or secretion of the chylomicron particle. PMID- 7980722 TI - Toward a better understanding of portal hypertensive gastropathy: the search for an ideal laboratory animal model. PMID- 7980723 TI - Effect of clonidine on myocardial ischaemia: a double-blind pilot trial. PMID- 7980724 TI - Efficacy of skin barrier creams (I). The repetitive irritation test (RIT) in the guinea pig. AB - An animal model for the evaluation of skin protective creams against chemical irritants is described. The irritants were applied daily for 2 weeks to shaved back skin of young guinea pigs: sodium lauryl sulphate (5% aq.; 30 min), sodium hydroxide (0.5% aq.; 2 min), and toluene (20% eth.; 2 min). The barrier cream was applied 2 h prior to and immediately after exposure to the irritant. Control animals were treated with the irritant only. The irritant reaction was scored on a 4-point scale for erythema and quantified with regard to transepidermal water loss (TEWL) by evaporimetry and skin blood flow volume (BFV) by laser Doppler velocimetry. A total of 90 guinea pigs, consisting of individual panels of 5 to 10 animals, was tested. While one barrier cream (Stokoderm) significantly suppressed the irritation due to sodium lauryl sulphate and toluene, the other (Contra-Alkali) failed to do so and even aggravated the response, which was particularly evident with sodium hydroxide. This model may be useful in developing more effective barrier creams. PMID- 7980725 TI - Fresh substrate essential for transketolase assay. PMID- 7980726 TI - Low serum cholesterol and suicide. AB - "Primary prevention trials which have shown that the lowering of serum cholesterol concentrations in middle-aged subjects by diet, drugs, or both leads to a decrease in coronary heart disease have also reported an increase in deaths due to suicide or violence. There has been no adequate explanation for this association. I have reviewed the relevant published work and describe a physiological mechanism that might account for this curious finding. One of the functions of serotonin in the central nervous system is the suppression of harmful behaviour impulses. When mouse brain synaptosomal membrane cholesterol is increased there is a pronounced increase in the number of serotonin receptors. Low membrane cholesterol decreases the number of serotonin receptors. Since membrane cholesterol exchanges freely with cholesterol in the surrounding medium, a lowered serum cholesterol concentration may contribute to a decrease in brain serotonin, with poorer suppression of aggressive behaviour". PMID- 7980727 TI - Air-weapon crimes and accidents: a source of preventable injury. PMID- 7980728 TI - Focal hyperintensities in cerebral white matter on MR images of asymptomatic volunteers: correlation with social and medical histories. AB - OBJECTIVE: Previous attempts to explain the presence of focal hyperintensities in the cerebral white matter on MR images have focused on the patient's age and cardiovascular risk factors. The purpose of this study was to survey many variables in subjects' social, medical, and surgical histories to identify those factors associated with focal hyperintensities in asymptomatic persons. SUBJECTS AND METHODS: Asymptomatic volunteers were examined with MR imaging of the head and questioned concerning smoking history; chemical dependence; alcohol consumption; medical history (e.g., high blood pressure, kidney disease); surgical history (e.g., for appendix, gallbladder); medications (e.g., antihypertensives, analgesics); and other historical family and social variables. Vital signs were recorded. Focal hyperintensities were counted by observers who were not provided any information about the subjects other than that they were either volunteers or patients. Each of the variables in the history was tested for an association with the number of focal hyperintensities seen on MR images. RESULTS: A statistically significant positive association was found between both age and the use of antihypertensive medications and the number of focal hyperintensities. Associations were also found between the number of focal hyperintensities and diastolic and systolic blood pressures at the time of MR imaging, but these associations did not reach statistical significance. No other variables in the medical, surgical, or social histories were found to be significantly related to the number of focal hyperintensities. CONCLUSION: Age and the use of antihypertensive medications were the only significant risk factors identified in respect to focal hyperintensities of the cerebral white matter. PMID- 7980729 TI - A deletion in the second exon of an HLA-DRB1 allele found in a DR2-negative narcolepsy patient. AB - In this report, we describe a new allele of the HLA-DRB 1 gene carrying a form of mutation that has not been observed before. It appeared in an HLA-DR2-negative narcolepsy patient who, besides HLA-DR4, revealed a serologic HLA-DR blank segregating with HLA-DQ1. Oligotyping showed that the new allele belongs to the HLA-DR8 group. Restriction analysis and DNA sequencing revealed the deletion of 12 bp as well as the substitution of 9 flanking base pairs between codons 36 and 43. The expression of the mutated gene was demonstrated by the presence of its messenger RNA and a few positive reactions with DR8 sera. Without interrupting the reading frame, the mutation leads to a gene product composed of a modified amino acid sequence. We anticipate that the mutation influences the conformation of the molecule with possible consequences concerning immune response. PMID- 7980730 TI - High levels of tumor necrosis factor-alpha and interleukin-6 in the ascitic fluid of cirrhotic patients with spontaneous bacterial peritonitis. AB - We prospectively measured the concentrations of immunoreactive tumor necrosis factor-alpha (TNF-alpha), interleukin-1 (IL-1), and interleukin-6 (IL-6) in the serum and ascitic fluid of 14 alcoholic cirrhotic patients with spontaneous bacterial peritonitis (SBP) and 16 alcoholic cirrhotic patients with sterile ascitic fluid. TNF-alpha levels in ascitic fluid were significantly higher for the patients with SBP: 399.57 +/- 129.23 pg/mL vs. 35.76 +/- 5.57 pg/mL (P < .001). IL-6 levels in ascitic fluid were also significantly higher for the patients with SBP: 170,713 +/- 57,109 ng/mL vs. 5,414 +/- 973 ng/mL (P < .001). By contrast, serum levels of TNF-alpha and IL-6 were just slightly more elevated than normal values. The concentration of IL-1 in the ascitic fluid of all patients was elevated, but there was no difference between patients with SBP or sterile ascites in this respect. In the patients with SBP, levels of TNF-alpha and IL-6 in ascitic fluid decreased during the first 48 hours of antibiotic treatment. Our results suggest that measurements of TNF-alpha and IL-6 in ascitic fluid may become useful markers both for the diagnosis of SBP and for monitoring the treatment of cirrhotic patients. PMID- 7980731 TI - Eruptive pseudoangiomatosis: a unique childhood exanthem? AB - We describe three children with an acute onset and spontaneous resolution of angioma-like papules during an apparent viral illness. A biopsy specimen from one patient revealed a unique histologic appearance that consisted of dilated dermal blood vessels with plump hobnail-shaped endothelial cells. On the basis of the natural history and histopathologic features of this exanthem, we suggest the name eruptive pseudoangiomatosis. PMID- 7980732 TI - What to do with limited view: the intumescent cataract. AB - In 1991, 2,967 consecutive cataract cases were analyzed in a prospective, observational study for the incidence of intumescent cataract. Thirty four (1.15%) of the cases were mature intumescent lenses. A deliberately small continuous curvilinear capsulorhexis (CCC) enlarged secondarily by the two-stage continuous curvilinear capsulorhexis (2-CCC) technique was the anterior capsulotomy approach of choice. Depending on the liquidity of the lens material, liquid cortex was aspirated using a 26- or 30-gauge needle before capsulorhexis or through a small CCC. Because of loss of CCC control, a can-opener capsulotomy was used in three of the 34 cases before being converted by the 2-CCC technique. The rigid nucleus was usually extracted using the down-slope nucleofractis phacoemulsification technique. Four (11.7%) of the 34 intumescent cases had anterior capsule tears during capsulotomy. Successful in-the-bag lens implantation was achieved in all cases. We describe a technique of CCC, 2-CCC, and down-slope sculpting nucleofractis phacoemulsification to manage intumescent cataracts. PMID- 7980733 TI - Trauma and trauma management. PMID- 7980734 TI - Selective erythroid replacement in murine beta-thalassemia using fetal hematopoietic stem cells. AB - We have explored the application of fetal hematopoietic stem cell (HSC) transplants for cellular replacement in a murine model of beta-thalassemia. Liver derived HSCs from nonthalassemic syngeneic murine fetal donors were transplanted into nonirradiated neonatal beta-thalassemic recipients. Significant erythrocyte chimerism (9-27%) was demonstrated in the majority of recipients at 1 month and remained stable or increased (up to 55%) during long-term follow-up in almost all cases. Chimeras had improved phenotypes, as evidenced by decreased reticulocyte counts, increased mean erythrocyte deformability, and decreased iron deposits in comparison to controls. To investigate whether the high degree of peripheral blood chimerism was predominantly a feature of erythroid elements or was a general feature of all hematopoietic elements, chimeras were created using donor HSCs "tagged" with a DNA transgene. Whereas donor hemoglobin comprised > 30% of total hemoglobin, nucleated tagged nonerythroid donor cells comprised < 1% of peripheral blood elements. Explanations for the observed selective increase in erythroid chimerism include longer survival of normal donor red cells compared to that of thalassemic red cells and the effective maturation of the donor erythroid elements in the bone marrow in chimeric animals. The latter explanation bears consideration because it is consistent with the process of ineffective erythropoiesis, well documented to occur in thalassemia, in which the majority of thalassemic erythroid cells are destroyed during erythropoiesis prior to release from the bone marrow. Overall, these data demonstrate the potential for significant erythroid chimerism and suggest that fetal HSC transplantation may play a significant role in future treatment. PMID- 7980735 TI - Early diagnosis of acute myocardial infarction: CK-MB and myoglobin compared. AB - We have measured changes in plasma concentration of creatine kinase MB (CK-MB) and myoglobin in 50 patients admitted to the Coronary Care Unit with chest pain of presumed cardiac origin. Eight serial blood samples were obtained in the 6 h period following admission and both CK-MB and myoglobin concentrations were measured. We compared the performance of single values of both tests. Myoglobin concentration, in the coronary care population studied, proved to be as specific as CK-MB concentration (92.6% in both cases) but with sensitivity of 100% being achieved 1.5 h post admission rather than 4 h post admission in the case of CK MB. On this evidence, measurement of plasma myoglobin could prove useful in the rapid diagnosis of myocardial infarction with consequent effects on optimal Coronary Care utilisation and selection of patients for thrombolytic therapy. PMID- 7980736 TI - Kinetics of enzymes with iso-mechanisms: analysis of product inhibition. AB - Isomerizations of free enzyme can be detected in kinetic patterns of product inhibition when the isomerization is partially rate-limiting. The kinetic pattern is non-competitive, owing to binding of substrate and product to different forms of free enzyme. This adds an additional term to the rate equation, sometimes represented as KSP. Several kineticists have noted that, as the rate of isomerization becomes high in relation to catalytic turnover, the intercept effect will become small, KSP will approach infinity, and the pattern will look competitive. Britton [(1973) Biochem. J. 133, 255-261] asserted that KSP will also approach infinity when the rate of isomerization becomes low. This second assertion is incorrect and can be traced to the particular model and graphical representation used to examine KSP as a function of relative rate constants. The function portrayed as a parabola with two roots for KSP is, instead, a straight line with one root. The algebraic condition justifying the second root obtains in the limit of zero in the rate of reaction and thus is not experimentally relevant, and the appearance of competitive inhibition, based on KSP alone, is not valid. Using a more general model, new equations are derived and presented which provide direct calculations of the apparent rate constants for free enzyme isomerizations from product-inhibition data when the equilibrium of the isomerization is near 1, and useful limits for the rate constants when greater than or less than 1. PMID- 7980737 TI - Potential impact of linking an emergency department and hospital-affiliated clinics to immunize pre-school-age children. AB - OBJECTIVE: To determine whether the use of an urban pediatric emergency department (ED) to immunize pre-school-age children would result in an improvement in the percentage fully vaccinated by the end of the second year of life. DESIGN: A retrospective cohort study of two groups: (1) 100 consecutive children (ED group) enrolled at one of two hospital-affiliated primary care clinics were chosen from the ED patient logs if their second birthday occurred in the 12 months prior to November 1990; and (2) 91 age-matched control children (control group) were chosen at random from the same hospital-affiliated clinics' enrollment logs without regard to ED use. The health care provided during the first 2 years of life for each group was compared. RESULTS: The mean number of visits to the ED in the first 2 years of life by the ED group was significantly greater than that of the control group (2.9 [SD] +/- 2.5 vs 1.1 +/- 1.4; P < .001) during the first 2 years of life. In 67% of ED visits, children would have been well enough to receive a vaccination. Both groups had similar types and numbers of visits to the primary clinics. For example, the ED group had 10 +/- 5 visits by age 2 years compared with the control group, which had 9 +/- 4 visits. There was no significant difference in actual immunization percentages achieved in the clinic, with 62% of the ED group having received four diphtheria, pertussis, and tetanus vaccinations; three oral poliovirus vaccinations; and one measles, mumps, and rubella vaccination by age 2 compared with 69% of control children. There were more missed vaccination opportunities during clinic visits in the ED group (7.4 vs 4.6 per 100 clinic visits; P < .01). If immunizations were offered in the ED to those children who needed them, immunization percentages would have been increased an average of 20% compared with percentages achieved in the clinic alone. CONCLUSION: Routine vaccinations in the ED would significantly increase immunization percentages in children enrolled in two hospital-affiliated clinics. Close linkage and coordination between the ED and hospital-affiliated clinics may improve preventive health care in urban children who use EDs. PMID- 7980738 TI - Passive immunity in the prevention of maternal-fetal transmission of human immunodeficiency virus infection. PMID- 7980739 TI - Cytoarchitecture of size-excluding compartments in living cells. AB - By fluorescence ratio imaging of large and small inert tracer particles in living cells, we have previously shown that particles 24 nm in radius are excluded from otherwise uncharacterized compartments in the distal and perinuclear cytoplasm (Luby-Phelps, K. and Taylor, D.L., 1988. Cell Motil. Cytoskel. 10, 28-37). In this study we examined the cytoarchitecture of these compartments. Whole-mount TEM showed that distal size-excluding compartments were devoid of membrane bounded organelles and were filled with a dense cytomatrix consisting of numerous, long bundles of thin filaments interconnected by a more random meshwork of short thin filaments. The mean diameter of void spaces in the cytomatrix of distal excluding compartments was 31 nm, compared to 53 nm in adjacent non excluding domains. The height of the distal excluding compartments was generally < or = 50% of the height in the adjacent non-excluding compartment. An electron dense structure having the same projected outline as the perinuclear size excluding compartment was visible by whole-mount TEM, but the cells were too thick and osmiophilic in this region to resolve any detail. Immunofluorescence localization of cytoskeletal proteins in distal excluding compartments indicated the presence of filament bundles containing F-actin nonmuscle filamin (ABP280) and alpha-actinin. F-actin and ABP280, but not alpha-actinin, were found also in between these filament bundles. Microtubules and vimentin generally were rare or absent from distal excluding domains. Staining of living cells with DMB-ceramide revealed that the perinuclear size-excluding compartment consisted of a compact, juxtanuclear domain coinciding with the trans-Golgi, surrounded by a more diffuse domain coinciding with a perinuclear concentration of endoplasmic reticulum. Intense immunofluorescence staining for vimentin was also observed in the perinuclear size-excluding compartment. We propose that the most likely mechanism for exclusion from distal compartments is molecular sieving by a meshwork of actin filament bundles interconnected by an F-actin/ABP280 gel network, while exclusion from the perinuclear compartment may be due to close apposition of cisternae in the trans-Golgi and a network or basket of vimentin filaments in the centrosomal region of the cell. PMID- 7980740 TI - Hepatic gene therapy: efficient retroviral-mediated gene transfer into rat hepatocytes in vivo. AB - The rat is an excellent model for gene therapy because there are many rat models for human diseases. We have developed a simple and efficient method to deliver genes to the rat liver using recombinant retroviral vectors. A 70% partial hepatectomy followed by retroviral infusion into the portal vein results in 10 15% hepatocyte transduction in vivo. This is 10 times more efficient than in the mouse due partially to the observation that the rat livers have much more synchronous hepatocyte replication after partial hepatectomy. Using a recombinant retroviral vector containing the human alpha 1-antitrypsin cDNA, persistent expression of the human protein in recipient rat plasma was observed for at least six months and at a level that is 10 times greater than the mouse. Thus, rats can serve as an excellent model for gene therapy of metabolic disorders secondary to hepatic deficiencies. PMID- 7980741 TI - Esophageal infections: risk factors, presentation, diagnosis, and treatment. AB - Infections of the esophagus are unusual in the general population and strongly imply immunodeficiency, although immunocompetent individuals are not exempt. HIV infection is predominant among risk factors for infectious esophagitis. For all immunocompromised patients, the most frequently identified esophageal pathogens are Candida, CMV, and HSV. Peculiar to HIV-infected patients are idiopathic esophageal ulcers as well as unusual bacteria and parasites. Patterns of presentation differ with each infecting organism, and clinical features should be used as a guide in achieving a correct diagnosis. For example, a patient with AIDS presenting with esophageal symptoms and thrush, along with abdominal pain, nausea, vomiting, and fever, is unlikely to resolve all symptoms with empiric antifungal therapy alone. Parsimony of diagnosis does not hold among immunodeficient patients in whom concurrent infections are common. Accurate and timely diagnoses are essential as effective treatments are available for particular etiologies. Finally, among immunocompromised patients, all esophageal symptoms are not necessarily due to an infection, and possible diagnoses of pill esophagitis, acid-peptic injury, or structural and functional abnormalities should not be overlooked. PMID- 7980742 TI - A critical review of the neurotoxicity of styrene in humans. AB - Styrene monomer is an aromatic industrial solvent. It is used to make polystyrene, resins, rubber, reinforced material and boats. Humans are exposed to styrene in occupational situations mostly during spraying processes at work, most of which is inhaled. The major neurotoxic effects of styrene as reviewed are prenarcotic effects, electroencephalographic abnormalities, slowing of motor, sensory and distribution nerve conduction velocities that reveal the possibility of polyneuropathy, dysfunction of the autonomic nervous system, slowing of reaction times, and centrally-controlled otoneurotoxicity. In acute exposure situations reversal of adverse effects has been observed; however, the impact of long-term exposure needs further studies. Dopamine depletion has been reported as a neurochemical basis of the neurotoxicity of styrene. Styrene epoxide, a toxic intermediate metabolite, has also been reported to deplete glutathione and cause lipid peroxidation, possibly leading to neuronal membrane damage. Raised concentrations of glial fibrillary acidic protein has been reported as an indicator of neurotoxicity in rats, which may damage the brain through astrogliosis phenomenon. This damage is also correlated to the toxic effects of styrene epoxide. Recently decreased monoamine oxidase type B activity in peripheral blood cells has been investigated as biochemical indicator of neurotoxicity of styrene in workers. There is a need for long-term studies, consideration of confounding factors (smoking, alcohol, diet, drugs, working environment and exposure to other solvents), and the effects on different ethnic and racial groups. More electroencephalographic studies and computer tomographic investigations are desired. Further reduction of the exposure limit to below 50 ppm is recommended. PMID- 7980743 TI - Climate change and human health. PMID- 7980744 TI - The ABC's of evaluating children with hematuria. AB - Hematuria is a common problem in children. Microscopic hematuria is more frequent than gross hematuria. Hematuria is often the initial finding in patients with urinary tract disease, and it is important to differentiate treatable renal involvement from untreatable, or benign, hematuria. The ABC's of hematuria in children were developed to teach the evaluation of children with hematuria to medical students and house staff. The ABC mnemonic helps physicians remember the differential diagnosis: Anatomy, Boulders, Cancer, Drug-related, Exercise, Foreign body, Glomerulonephritis, Hematology and Infection. A clinical algorithm is provided to guide the evaluation of children with hematuria. PMID- 7980745 TI - Communication within the emergency department: how do you get the word out? PMID- 7980746 TI - Law and ethics. PMID- 7980747 TI - Empirical H2-blocker therapy or prompt endoscopy in management of dyspepsia. AB - The recommended strategy for management of dyspepsia is empirical treatment with an H2-blocking drug, followed by endoscopy if the symptoms do not respond or recur. We compared two strategies for the management of dyspepsia--treatment based on the results of prompt endoscopy (group 1) and empirical H2-blocker treatment with diagnostic endoscopy only in cases of therapeutic failure or symptomatic relapse within 1 year (group 2). Eligible patients had symptoms severe enough to justify empirical H2-blocker therapy. Symptoms, drug consumption, and sick-leave days were assessed through monthly diaries. Patients with non-organic dyspepsia diagnosed by endoscopy did not receive ulcer drugs. Of 414 patients randomised, 373 completed 1-year follow-up. Organic disease was found at endoscopy in 68 (33%) of 208 group-1 patients (ulcer in 45). Endoscopy was done in 136 (66%) of 206 group-2 patients. Case selection for endoscopy was not improved by the empirical treatment strategy, since the diagnostic profile was the same as in group 1 and 40% of the expected ulcer cases remained undiagnosed. After 1 year there were no differences in symptoms or quality of life measures. The empirical treatment strategy in dyspepsia was associated with higher costs, due mainly to a higher number of sick-leave days and cost of ulcer drug use. Prompt endoscopy is a cost-effective strategy in dyspeptic patients with symptoms severe enough to justify the current practice of empirical H2 blocker treatment. PMID- 7980748 TI - Maternal postnatal depression and infant gastro-oesophageal reflux. PMID- 7980749 TI - "Cholinergic score" and delirium. PMID- 7980750 TI - A surgical approach to the sublingual salivary gland. AB - A new surgical approach to the sublingual salivary gland is described, the key feature of which is the use of a flap rather than the usual incision. The flap includes the submandibular duct and, because of the relationship of the duct and lingual nerve, allows early identification of the latter before dissection of the gland. Improved access also simplifies dissection of the gland, particularly on its deep aspects where troublesome bleeding may be encountered. PMID- 7980752 TI - [Neurologic deficiency disease in the 90's]. PMID- 7980751 TI - An evaluation of the effectiveness, safety and acceptability of a nurse practitioner in a rheumatology outpatient clinic. AB - Seventy patients with RA were randomly allocated to either a Rheumatology Nurse Practitioner (RNP) or Consultant Rheumatologist (CR) clinic. They were seen on six occasions in 1 year. Effectiveness and safety were assessed by biochemical, clinical, psychological and functional variables; patient knowledge and satisfaction were measured by questionnaire. At week 0 the groups were well matched clinically and demographically. By week 48 significant improvements had occurred in plasma viscosity and articular index within both groups. In patients managed by the RNP, pain, morning stiffness, psychological status, patient knowledge and satisfaction had all improved significantly (P = 0.001; P = 0.028; P = 0.0005; P < 0.0001; P < 0.0001 respectively), improvements not mirrored by the CR cohort. Between group comparisons also showed significant differences by the end of the study. Compared to the CR patients, the RNP suffered from lower levels of pain (P < 0.05), had acquired greater levels of knowledge (P < 0.0001) and were significantly more satisfied with their care (P < 0.0001). PMID- 7980753 TI - Adhesive systems: composites, dentine bonding agents and glass ionomers. AB - The urge by manufacturers to develop new and better materials can often leave the dentist confused as to how they work. This article seeks to describe these materials simply and how they can best be made to work; it may also help practitioners to ask representatives leading questions when presented with the latest product. PMID- 7980754 TI - Private medicine takes on the NHS in Britain. PMID- 7980755 TI - Professional norms and physician attitudes toward euthanasia. PMID- 7980756 TI - An outbreak of foodborne streptococcal throat infection. AB - Streptococcal pharyngitis is a common disease of epidemic nature, usually transmitted by saliva droplets. We present an epidemiologic analysis of an outbreak of streptococcal pharyngitis in a military unit involving 75 soldiers. The causing organism was Streptococcus pyogenes (group A beta hemolytic Streptococcus, T28 M56), which was isolated from 53 affected individuals. The source of the epidemic was probably an army cook. The infection was transferred by a cabbage salad to individuals who became symptomatic within 24-48 h. This epidemic is a reminder of an exceptional route of streptococcal dissemination and one of the largest outbreaks of foodborne streptococcal pharyngitis documented. PMID- 7980757 TI - Take two glasses of wine and see me in the morning. PMID- 7980758 TI - Concurrent childhood and adult excesses of leukaemia in geographical areas. PMID- 7980759 TI - Roxithromycin and lower respiratory tract infections. PMID- 7980761 TI - QALYs for resource allocation: a reply to Burrows and Brown. PMID- 7980760 TI - Periodic health examination, 1994 update: 2. Screening strategies for colorectal cancer. Canadian Task Force on the Periodic Health Examination. AB - OBJECTIVE: To make recommendations on the effectiveness of screening for colorectal cancer in asymptomatic patients over 40 years of age. OPTIONS: Multiphase screening that begins with test for fecal occult blood, uniphase screening with sigmoidoscopy and uniphase screening with colonoscopy. Options included screening repeated at different intervals and different procedures for patients with selected risk factors. OUTCOMES: Rates of death, death from cancer and cancer detection; compliance, feasibility and accuracy of each manoeuvre. EVIDENCE: A MEDLINE search for articles published between January 1966 and June 1993 with the use of MeSH terms "screening" and "colorectal neoplasia," a check with the reference sections of review articles published before June 1993 and a survey of content experts. Articles were weighted according to the Canadian Task Force on the Periodic Health Examination levels of evidence. VALUES: The highest value was assigned to manoeuvres that lowered the rate of death from cancer and had a low rate of false-positive results and acceptable cost and compliance. Recommendations were determined by consensus of the authors, members of the task force and colorectal cancer experts. BENEFITS, HARMS AND COSTS: There is evidence that annual fecal occult blood testing with the use of the rehydrated Hemoccult test has a small but significant benefit in lowering the rate of death from cancer after more than 10 years of screening; however, the high rate of false positive results (9.8%) and the poor sensitivity of annual (49%) and biennial (38%) screening make this a poor method for detecting colorectal cancer. There is fair evidence that screening with sigmoidoscopy may improve survival rates; however, this may be due to volunteer bias. The high cost of and poor compliance with colonoscopic screening make this an unfeasible strategy. PMID- 7980762 TI - Confidential bedwetting hotline. PMID- 7980763 TI - Evaluating Bhola's Configurations Theory of Planned Change. AB - In Bhola's Configurations Theory of Planned Change, the CLER Structure resides in the midst of an epistemic triangle comprised of systems theory, dialectical thinking and constructivism. Our evaluation process compared the theory with descriptive statements in the Tiffany/Lutjens Planned Change Theory Evaluation Scale and found that Bhola's Theory resonates well with nursing's needs. This suggests its application to nursing's clinical, education, administrative, and research settings. PMID- 7980764 TI - Relation between myocardial infarct location and stroke. AB - OBJECTIVES: We sought to compare the likelihood of stroke in patients with anterior versus nonanterior myocardial infarction. BACKGROUND: The association between anterior infarction and left ventricular thrombus has led to the assumption that embolization from thrombi is an important cause of stroke in patients with anterior infarction. We hypothesized that if anterior infarction is a cause of left ventricular thrombi, the number of strokes should be disproportionately higher in patients with anterior than nonanterior infarction. METHODS: We performed a retrospective analysis of 2,466 patients randomized from day 3 to day 15 after infarction as part of a multicenter placebo-controlled study of diltiazem to prevent cardiac death or myocardial infarction. Any acute focal cerebral disorder resulting in localizing findings characterized as a stroke or transient ischemic attack was considered an event. RESULTS: Of 91 events during a follow-up period of 12 to 52 months, 23 (3.2%) occurred in 724 patients with an anterior and 68 (3.9%) in 1,742 patients with a nonanterior myocardial infarction (relative risk 0.81; 95% confidence interval 0.51 to 1.30). Power analysis revealed that the negativity of the study was not the result of inadequate sample size. Life table analysis showed no difference in cumulative event rate (p = 0.42) according to site of infarction. Cox regression analysis showed that of 10 clinical covariates, only systolic blood pressure was predictive of stroke (p < 0.001). The use of warfarin did not contribute to the model. Finally, the addition of site of infarction (anterior vs. nonanterior) did not contribute significantly to the Cox model. CONCLUSIONS: Although there is a significant incidence of stroke after acute myocardial infarction, there is no relation between the occurrence of stroke and site of infarction. These data do not support the presumed causal relation between anterior myocardial infarction, thrombus and stroke. PMID- 7980765 TI - Temporal patterns in colorectal cancer incidence, survival, and mortality from 1950 through 1990. AB - BACKGROUND: Colorectal cancer mortality rates among U.S. white males remained relatively constant from 1950 through 1984 but declined sharply from 1985 through 1990. Those for U.S. white females decreased consistently from 1950 through 1984, with an acceleration of the decline from 1985 through 1990. PURPOSE: A study was planned to investigate patterns in incidence, survival, and mortality rates over time in order to examine possible reasons for the gender difference in mortality trends and for the decrease in the slope of the mortality trends for both males and females in the late 1980s. METHODS: Incidence and survival data from the Connecticut Cancer Registry were examined to investigate the gender differences in mortality rates from 1950 through 1984. Incidence and survival data from the Surveillance, Epidemiology, and End Results (SEER) Program were investigated to examine reasons for the abrupt downturn in mortality rates for both white males and white females beginning around 1985. RESULTS: During the period 1950 through 1984, the colorectal cancer incidence rates in Connecticut increased for males and declined slightly for females. Survival rates were similar for both sexes, increasing on average over 1% per year for both females and males from 1950 through 1984. Examination of SEER data from 1975 through 1990 revealed that for both males and females there were 1) declines in overall incidence and mortality rates beginning in the mid-1980s, 2) steady declines in distant disease incidence rates since 1975, 3) increases in regional disease incidence rates until the early 1980s followed by declines in the late 1980s, and 4) increases in local disease incidence rates until the mid-1980s followed by declines in the late 1980s. Age-period-cohort analyses of mortality rates indicated a statistically significant moderation of colorectal cancer risk with both advancing birth cohorts and recent calendar periods. CONCLUSIONS: The gender differences in colorectal cancer mortality rate trends observed from 1950 through 1984 are due to differences in incidence rate trends between males and females. Declining colorectal mortality rates in the late 1980s for males and females appear to reflect improved early detection. The peaking and subsequent decline of stage specific incidence rates at later years for successively lower stage indicate sequential stage shifts as cancers are detected increasingly earlier over time. The increased use of sigmoidoscopy and fecal occult blood tests (triggering colonoscopy) appears to have played an important role in reducing colorectal cancer mortality. Improvements in birth cohort trends in risk for colorectal cancer for each sex suggest that lifestyle changes may have also contributed to the steady reductions in colorectal cancer mortality. PMID- 7980766 TI - Tuberculosis treatment programmes in low-income countries. PMID- 7980767 TI - Health care for the elderly: consultants in care. PMID- 7980768 TI - Cholera. Lessons from the epidemic in Peru. AB - It is not known why the cholera epidemic, which affected all other continents, has not affected Latin America in the past 30 years. In addition, it is unclear why cholera appeared in Peru in 1991. Improvements in scientific knowledge and technology have occurred in Peru during the last 30 months. While it is impossible to summarize in only one article all these concepts, this article presents a few of the most important issues and recent developments in the treatment and prevention of cholera. PMID- 7980769 TI - Positron emission tomography imaging of the thorax. AB - Positron emission tomography (PET) is just beginning to emerge as a clinically useful tool in the thorax. Imaging with FDG is used primarily to differentiate benign from malignant abnormalities, including solitary pulmonary nodules, staging bronchogenic carcinoma, and differentiating recurrent tumor from fibrosis following treatment. This article discusses the fundamental properties of PET images, techniques, and current clinical indications in the thorax. PMID- 7980771 TI - Product inhibition in mechanisms in which the free enzyme isomerizes. PMID- 7980770 TI - New targets for pyrimidine antimetabolites for the treatment of solid tumours. 2: Deoxycytidine kinase. AB - Deoxycytidine kinase is an enzyme required for the activation of, for example, cytarabine, the most widely used agent for the chemotherapy of haematological malignancies. However, deoxycytidine kinase also plays an important role in the activation of several new agents used in the treatment of leukaemia, such as cladribine. Recently, a new cytidine analogue, gemcitabine, has shown impressive activity as a single agent against several solid malignancies (ovarian cancer, non-small cell lung cancer), demonstrating that in solid tumours deoxycytidine kinase can be an important target for the activation of antimetabolites. Studies on the regulation of deoxycytidine kinase have shown that the enzyme has a complicated regulation (feedback inhibition by the product and regulation by ribonucleotides). Modulation of deoxycytidine kinase activity has already been shown to be an effective way to improve the effect of cytarabine and will probably be a target for new therapies. PMID- 7980772 TI - Orthologic prize case reports (1990). PMID- 7980773 TI - Toxocara canis and human health. PMID- 7980774 TI - Improving education through computer-based training. PMID- 7980775 TI - Randomized trial of drainage of colorectal anastomosis. PMID- 7980776 TI - Peripheral versus central intravenous nutrition: comparison of two delivery systems. PMID- 7980777 TI - Midazolam and status epilepticus in children. PMID- 7980778 TI - Who says being a doctor is still fun? PMID- 7980779 TI - Urinary incontinence in elderly females. AB - This article reviews recent literature regarding the incidence, causes, and treatment of urinary incontinence in elderly women. Data gathering was based upon a Medline search of the medical literature from 1987 to 1993. Studies that included fifty subjects or more and that were published in a physician-oriented journal were selected for inclusion. The findings indicate that urinary incontinence is a common problem among elderly women and one that can be easily evaluated and treated, at least initially, in any physician's office. PMID- 7980781 TI - Bedwetting hotline. PMID- 7980780 TI - Myocardial infarction: ACE inhibitors for all? For ever? PMID- 7980783 TI - Strategies for ED communication. PMID- 7980782 TI - Isolation and characterization of human immunodeficiency virus type 1 variants infectious to brain-derived cells: detection of common point mutations in the V3 region of the env gene of the variants. AB - T-cell-line-tropic human immunodeficiency virus type 1 cannot infect CD4 positive, brain-derived cells. We isolated several new variants that readily infected brain-derived cells. Mutation of proline to serine, to alanine, or to threonine in the well-conserved GPGR sequence in the V3 region of the envelope glycoprotein was found in all these variants. This indicates the importance of amino acid sequences at the tip of the V3 region for brain cell tropism of human immunodeficiency virus type 1. PMID- 7980784 TI - Cladribine treatment of multiple sclerosis. PMID- 7980785 TI - Cladribine treatment of multiple sclerosis. PMID- 7980786 TI - Toxoplasmosis in pregnancy. PMID- 7980787 TI - HIV and lesbian sex. PMID- 7980788 TI - Endothelial dysfunction in hypertension. PMID- 7980789 TI - Fourth generation dentine bonding agents. PMID- 7980790 TI - Central venous catheter placement and complications. PMID- 7980791 TI - Response to "Early emergent coronary bypass after failed angioplasty". PMID- 7980792 TI - Capsular endodiathermy and intumescent cataract. PMID- 7980793 TI - Laparoscopic hernia repair. PMID- 7980794 TI - Complete bilateral distal ureteral obstruction after appendicectomy. PMID- 7980795 TI - Effects of tamoxifen on uterus. PMID- 7980796 TI - Effects of tamoxifen on uterus. PMID- 7980797 TI - A different view of guns. PMID- 7980798 TI - Cerebral artery blood flow during laparoscopic cholecystectomy. PMID- 7980799 TI - Opioid antagonist adjuncts to epidural morphine for postcesarean analgesia: maternal outcomes. PMID- 7980800 TI - Complications of tracheostomy in major head and neck cancer surgery; a retrospective study of 60 consecutive cases (Br J Oral Maxillofac Surg 1994; 32: 3-5) PMID- 7980801 TI - Practical Bayesian guidelines for phase IIB clinical trials. AB - A Phase IIB clinical trial typically is a single-arm study aimed at deciding whether a new treatment E is sufficiently promising, relative to a standard therapy, S, to include in a large-scale randomized trial. Thus, Phase IIB trials are inherently comparative even though a standard therapy arm usually is not included. Uncertainty regarding the response rate theta s of S is rarely made explicit, either in planning the trial or interpreting its results. We propose practical Bayesian guidelines for deciding whether E is promising relative to S in settings where patient response is binary and the data are monitored continuously. The design requires specification of an informative prior for theta s, a targeted improvement for E, and bounds on the allowed sample size. No explicit specification of a loss function is required. Sampling continues until E is shown to be either promising or not promising relative to S with high posterior probability, or the maximum sample size is reached. The design provides decision boundaries, a probability distribution for the sample size at termination, and operating characteristics under fixed response probabilities with E. PMID- 7980802 TI - Questions about the role of granulocyte-macrophage colony-stimulating factor as adjunct to non-Hodgkin's lymphoma chemotherapy. PMID- 7980803 TI - Cancer prevention in primary care. Screening for cervical cancer. AB - Cervical screening has been shown to be effective in several countries, although not by means of randomised controlled trials. A screening programme has been in operation in the United Kingdom since 1964, but it has, in the past, been beset with problems of organisation, accountability, and commitment. The introduction in 1988 of a systematic call and recall introduction in 1988 of a systematic call and recall system and the setting up of an NHS cervical screening programme national coordinating network has brought a greater sense of coherence. Coverage of the target population in England between 1989-90 and 1992-3 increased from 61% to 83%, and there is a strong indication that cervical screening is now beginning to reach those most at risk--namely, older women from lower social classes. Primary care is central to the overall success of the cervical screening programme. General practitioners are in a unique position to invite women for a smear test, to take smears, to ensure that abnormal smear test results are followed up, and to check on reasons for non-attendance. Numerous studies have looked at the involvement of general practice in cervical screening, identifying many ways in which the programme can be improved. Many practices are now running well organised and effective programmes. PMID- 7980804 TI - Correspondence Re: D. G. Brachman et al., Mutation does not correlate with radiosensitivity in 24 head and neck cancer cell lines. Cancer Res., 53: 3667 3669, 1993. PMID- 7980805 TI - Clonidine and postoperative myocardial ischaemia. PMID- 7980806 TI - Assay of glucose in urine by near-infrared spectrophotometry. PMID- 7980807 TI - The calendar vs. cervical mucus. PMID- 7980808 TI - Serotonergic agents and frontal lobe syndrome. PMID- 7980809 TI - The scintigraphic sign for detection of right-to-left shunts. PMID- 7980810 TI - Treating hyperthyroidism with radioiodine. PMID- 7980811 TI - May randoms evolve into scatter? PMID- 7980812 TI - Re: Effect of sunscreens on UV radiation-induced enhancement of melanoma growth in mice. PMID- 7980813 TI - Influence of some traditional medicinal plants of Senegal on prostaglandin biosynthesis. AB - Aqueous extracts of Combretum micranthum G. Don, Euphorbia hirta L., Guiera senegalensis Lam. and Melaleuca leucadendron L. were investigated for their influence on prostaglandin biosynthesis (PG I2, PG E2, PG D2). Only the extract of Euphorbia hirta strongly reduced the release of prostaglandins I2, E2, and D2. Additionally Euphorbia hirta extracts exerted an inhibitory effect on platelet aggregation and depressed the formation of carrageenin induced rat paw oedema. The chemical nature of the active principle of Euphorbia hirta could be characterized as (a) compound(s) of medium polarity in the molecular weight range of 1000 to 3000 Da. PMID- 7980814 TI - Dorothy Hodgkin (1910-94) PMID- 7980815 TI - No smoking. PMID- 7980816 TI - Anterior choroidal artery territory infarcts. PMID- 7980817 TI - Controversies in transfusion medicine: is autologous blood transfusion worth the cost? Pro. PMID- 7980818 TI - MRI of the knee: its cost-effective use in a district general hospital. PMID- 7980819 TI - Myths of dental-induced endocarditis. PMID- 7980820 TI - Role of psychiatry in the academic health sciences center. PMID- 7980821 TI - Failure to demonstrate prophylactic efficacy of dothiepin. PMID- 7980822 TI - A tool for living through stress. AB - To move beyond illness-directed behaviors, a Recognizing/Needing graph directs nurses to present environmental stressors, needs and suggestions for future interventions. Assessment questions focus on illuminating meaning, synchronizing rhythms, and mobilizing transcendence, encouraging them to adopt health-directed behaviors. PMID- 7980823 TI - Sexual development of malaria parasites is inhibited in vitro by the neem extract azadirachtin, and its semi-synthetic analogues. AB - We have shown that azadirachtin, a compound from the neem tree, Azadirachta indica, and selected semi-synthetic derivatives, block the development of the motile male malarial gamete in vitro. Changes in the hemiacetal group at position C11 in the molecule result in a loss of activity in this assay. The motility of fully formed male gametes, and other selected flagellated cells, is unaffected by azadirachtin in vitro. These findings raise the possibility of developing azadirachtin-based compounds as antimalarials with transmission-blocking potential, as well as permitting the further study of structure-activity relationships in these compounds. PMID- 7980824 TI - Immunohistologic p53 expression in normal skin. PMID- 7980825 TI - Misconceptions about nasal ventilation. PMID- 7980826 TI - Absolute effects of relative poverty. PMID- 7980827 TI - Plagiarism. Anonymous reference: a contradiction in terms? PMID- 7980828 TI - Tenth percentiles of kidney length in adult volunteers. PMID- 7980829 TI - Achalasia and esophageal carcinoma. PMID- 7980830 TI - The use of potassium channel blocking agents in the therapy of demyelinating diseases. PMID- 7980831 TI - The impact of response options and location in a microcomputer interview on drinking drivers' alcohol use self-reports. AB - The influence of response options for and location of frequency of alcohol use items in a self-administered microcomputer interview were evaluated in a randomized, experimental study of 296 clients at a west coast treatment site for drinking drivers. Respondents were asked about their frequency of alcohol use in the last 7 days, 30 days, 90 days, and 180 days with three methodological factors randomized: (1) how quantitative the response options were; (2) order of presentation of close-ended response options; and (3) relative placement of alcohol use items in the questionnaire. Results indicate that these methodological factors had minimal influence on self-reports of the frequency of alcohol use. Only two statistically significant effects out of 44 possible were observed. The findings of this study suggest that frequency of alcohol use reports by drinking drivers yield similar information for a range of different response formats and location of the items in a microcomputer interview. PMID- 7980832 TI - Collaborative interdisciplinary bioethical decision making in intensive care units. PMID- 7980833 TI - Cytokines and infection in patients with cirrhosis. PMID- 7980834 TI - Iatrogenic meningitis due to Streptococcus salivarius. PMID- 7980835 TI - Expression of mRNA encoding FMRFamide-related peptides (FaRPs) in the nervous system of Helix aspersa. AB - The FMRFamide-related peptides (FaRPs) of Helix fall into two groups with often different pharmacological effects: the tetrapeptides FMRFamide and FLRFamide (tetraFaRPs) and the heptapeptides, which have the general structure XDP(F or Y)LRFamide (heptaFaRPs). Previously, we have shown that each group of FaRPs is encoded within a separate type of cDNA clone, a situation which corresponds to two distinct mRNA species existing in the CNS of Helix. Here, we report on the expression patterns of the two FaRP mRNAs both through embryo-genesis and in the fully differentiated regions of the adult nervous system. The levels and locations of FaRP mRNAs were studied by molecular and in situ hybridization using antisense riboprobes. The onset of expression of FaRP mRNAs occurs in Helix embryos about half-way between egg laying and hatching. First detection of the FaRPs themselves occurs about 2 days later. In embryos, as in the adult CNS, the heptaFaRP mRNA is at least five times more abundant than the tetraFaRP mRNA. In adults, the tetraFaRP mRNA is located primarily in the cerebral ganglia, most obviously in the C3 neuron, but also in a crescent-shaped cluster of small neurons lying anterior to C3. Occasional neurons expressing the tetraFaRP mRNA are detected in the parietal ganglia, but these have not yet been mapped. In contrast, the heptaFaRP mRNA is expressed almost exclusively in the parietal ganglia: in large clusters of about 100 neurons lying near to the anterior surface. The most interesting aspect of FaRP mRNAs is that their expression is not only exclusive to a relatively small number of specified neurons, but that expression appears to be mutually exclusive, that is, a particular neuron expresses only the mRNA for tetra-FaRPs or heptaFaRPs, never both. These results are discussed in relation to what we now know about the structure of the individual mRNA molecules. PMID- 7980836 TI - Primary care. Participants or gatekeepers? AB - Health systems that have a strong orientation toward primary care achieve lower overall costs, better satisfaction of their populations, and better health. The role of specialists in such systems is to provide consultative services on a short-term basis (secondary care) or long-term services for rare or complicated problems (tertiary care). Among both primary-care and specialist physicians, opinions vary considerably as to the specific tasks that are appropriate in primary and specialist care. Medical education has not proved an adequate basis for judging either the relative appropriateness of care by primary-care physicians and specialists or criteria for referral. Recent studies indicate that conventional wisdom concerning the nature and treatment of disease that is derived from research in tertiary medical centers is contradicted by collaborative practice-based studies in primary care. Better collaboration between primary-care physicians and specialists both in research and in the design of services will be the key to more informed decisions about improvement in the care of patients with diabetes and other important and common health-care problems. PMID- 7980837 TI - Evaluation of cassava-salt suspension in the management of acute diarrhoea in infants and children. AB - To identify a suitable substrate for an oral rehydration solution (ORS) at home, this study evaluated the efficacy and safety of cassava-salt suspension (CSS) prepared from a dietary staple, cassava, with added sodium chloride. The results were compared with those of standard World Health Organization (WHO) recommended ORS. One hundred thirty-two dehydrated children aged between 6 and 24 months with acute diarrhoea of less than 3 days duration were chosen for the study and randomly rehydrated with CSS or WHO-ORS. The intake of ORS (CSS or WHO-ORS), water, and food was comparable in both groups. The mean stool output on day 1, total stool output, and duration of diarrhoea were 45.3 +/- 37.3 g/kg, 60.8 +/- 58.9 g/kg, and 18.9 +/- 22.4 h for the group on CSS. These are significantly different from the corresponding values of 69.7 +/- 64.9 g/kg, 88.2 +/- 100.4 g/kg, and 28.2 +/- 27.0 h obtained for controls. Failure of therapy occurred in four children on CSS (6%) and three children on WHO-ORS (4.5%). It is concluded that CSS is both efficacious and safe for use as an ORS, particularly in the home management of acute diarrhoea in children. PMID- 7980838 TI - Isoflurane-induced coronary vasodilation. PMID- 7980839 TI - Hormone-nuclear receptor interactions in health and disease. Glucocorticoid resistance. AB - Familial glucocorticoid resistance results from the partial inability of glucocorticoids to exert their effects on their target tissues throughout the organism. The condition is associated with compensatory elevations of circulating ACTH and cortisol, with the former causing excess abnormal secretion of steroids with mineralocorticoid and androgen activity. The manifestations of glucocorticoid resistance vary from asymptomatic to chronic fatigue, to varying degrees of hypertension and/or hypokalaemic alkalosis and hyperandrogenism. The latter can be manifest in women as acne, hirsutism, menstrual irregularity, oligoanovulation and infertility, in men as infertility, and in children as precocious puberty. Different molecular defects of the highly conserved glucocorticoid receptor gene, altering its concentration and functional characteristics, appear to cause the syndrome of familial glucocorticoid resistance. Depending on the molecular defect, this syndrome is transmitted by an autosomal dominant or recessive trait. There are recent suggestions that non generalized forms of glucocorticoid resistance may exist, resulting in autoimmune inflammatory phenomena or psychiatric manifestations. PMID- 7980840 TI - Streptokinase antibodies are of clinical importance and they can be measured in half an hour by a simple enzyme-linked immunosorbent assay. PMID- 7980841 TI - Ileal and colonic epithelial metabolism in quiescent ulcerative colitis. PMID- 7980842 TI - Breast cancer: treatment differences and survival. PMID- 7980843 TI - F-wave quantitation in neuropathy. PMID- 7980844 TI - Re: "Inconsistent associations of caffeine-containing beverages with blood pressure and with lipoproteins: the CARDIA Study". PMID- 7980845 TI - Re: "Age and season of birth in sudden infant death syndrome in North Carolina, 1982-1987: no interaction". PMID- 7980846 TI - Natural autoantibodies are involved in the haemolytic anaemia of NZB mice. AB - NZB is a mouse strain that spontaneously develops autoimmune haemolytic anaemia at 10-12 months of age. We analysed the autoantibodies present throughout their life and compared them to natural autoantibodies found in the normal mouse. Sera and Coombs' antibodies eluted from red blood cells (RBC) were tested for their activities against RBC and a panel of antigens: actin, myoglobin, myosin, tubulin, spectrin, DNA and trinitrophenyl bovine serum albumin (TNP-BSA), F(ab')2 and Fc fragments of IgG by using enzyme immunoassays (EIA) and Western blotting analysis of RBC membrane extracts. In NZB mouse sera, activities of IgM and IgG against the whole panel, compared to those of sera from age-matched BALB/c mice, increased progressively throughout life with oscillating values in parallel with the anti-RBC activity. Two periods of autoantibody production seem to exist: the first is characterized by a fluctuating high level of IgM and stable level of IgG natural autoantibodies, and the second by a rise of IgG natural autoantibodies in parallel with IgG anti-RBC antibodies. The presence of idiotype D23 (IdD23), which is characteristic of natural polyspecific autoantibodies, was high on serum IgM and low on IgG autoantibodies throughout life. To further analyse autoantibody level oscillations, we tested IgM and IgG fractions after their separation from whole serum and observed highly enhanced autoantibody activities of both IgM and IgG. These autoreactivities markedly diminished when the separated IgM and IgG fractions were recombined, suggesting humoral control of the autoreactivity as we had already noted for IgG in normal animals. During the first period of autoantibody production, IgM and IgG antibodies eluted from RBC (Combs' antibodies) and those eluted from serum using an RBC-immunoadsorbent (circulating antibodies) reacted with all RBC membrane components, with all antigens of the panel and with F(ab')2 and Fc. Some of these reactivities were comparable to those exhibited by a monoclonal antibody recognizing bromelain treated RBC. In the second period, both IgM and IgG Coombs' antibodies reacted more strongly with spectrin, and exhibited new specificities, for example against the band 3 polypeptide. IdD23 was abundant on Combs' IgG antibodies in the second period. Taken together, these data suggest that IgM and IgG natural autoantibodies, able to recognize not only RBC antigens but also other antigens, particularly F(ab')2 and Fc fragment of IgG, predominate in Coomb's antibody population.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 7980848 TI - Anti-phospholipid antibodies in the mercuric chloride treated brown Norway rat. AB - Anti-phospholipid antibodies (aPL), in the form of anti-cardiolipin antibodies (aCL) and/or lupus anticoagulant (LAC), are found in a number of disorders, including systemic lupus erythematosus. Autoimmune aPL are associated with clinical manifestations that may include vascular thrombosis, recurrent fetal loss, thrombocytopenia, livedo reticularis and neurological abnormalities. aPL found in the context of infections such as syphilis are not usually associated with clinical complications. Here we report the presence of aCL in Brown Norway (BN) rats treated with mercuric chloride (HgCl2), which is known to induce a number of other autoantibodies. Some also showed LAC activity as shown by extension of the kaolin clotting test time. The binding of human autoimmune aPL is known to be considerably enhanced by a serum cofactor, beta 2-glycoprotein I; only slight enhancement, and in some cases inhibition, was found with BN rat aPL. These results indicate that aPL can be added to the list of autoantibodies that have been documented in the HgCl2 treated BN rat. The effect of addition of serum co-factor suggests that these are most closely related to human infection associated (as opposed to autoimmune) aPL. PMID- 7980847 TI - Immunization with anticardiolipin cofactor (beta-2-glycoprotein I) induces experimental antiphospholipid syndrome in naive mice. AB - Beta-2-GPI is a 50 kDa glycoprotein which is known to be a serum co-factor, with a role in determining the binding of pathogenic anticardiolipin antibodies to phospholipids. Immunization of naive mice with beta-2-GPI resulted in elevated levels of antibodies directed against negatively charged phospholipids (cardiolipin, phosphotidylserine, phosphatidylinositol). The presence of increased titres of antiphospholipid antibodies in the sera of the mice was later followed by prolonged activated partial thromboplastin time (APTT), thrombocytopenia, and when the mice were mated, by a high percentage of fetal resorptions in the uterus. These data point to the ability of beta-2-GPI to induce pathogenic anti-cardiolipin antibodies following active immunization. PMID- 7980849 TI - A region on the human thyrotropin receptor which can induce antibodies that inhibit thyrotropin-mediated activation of in vitro thyroid cell function also contains a highly immunogenic epitope. AB - Autoantibodies to the thyrotropin receptor (TSHr) bind to the extracellular domain of the TSHr (ETSHr) and either stimulate or inhibit thyroid cell function and/or growth. In order to investigate the regulation and the specificity of the immune response to the TSHr, our laboratory recently produced recombinant human ETSHr protein by using the baculovirus expression system. In the present study, we used the recombinant ETSHr protein, a panel of overlapping synthetic peptides derived from the TSHr, and polyclonal rabbit antibodies produced against recombinant ETSHr and synthetic peptides to define a highly immunogenic region (aa 352-388) of the TSHr. Moreover, we used competitive inhibition studies to identify a dominant epitope (aa 367-372) within this region to which ETSHr antibodies react. This immunodominant epitope lies within a region unique to the TSHr when compared to the other glycoprotein hormone receptors. These data, together with the earlier observation that antibodies against aa region 357-372 can inhibit thyrotropin (TSH)-mediated activation of thyroid cells in culture, show that aa 367-372 represents, an immunodominant epitope within a functionally important region which is unique to the TSHr. Therefore, this region may play an important role in the induction or modulation of the specific immune response against the TSHr. PMID- 7980850 TI - Lack of relationship between the Epstein-Barr virus and the antiperinuclear factor/'perinuclear antigen' system in rheumatoid arthritis. AB - Our purpose was to evaluate the role of Epstein-Barr virus (EBV) in the production of antiperinuclear factor (APF), a rheumatoid arthritis (RA)-specific marker, and the autoimmunogenicity of 'perinuclear antigens' (PNA) found within the buccal mucosa epithelial cells used as a substrate in the APF assay. Fifty APF-positive and 50 APF-negative sera from RA patients were examined for the presence of antibodies to six different EBV antigens. APF was tested in the serum of 40 patients with acute infectious mononucleosis (IM), 48 PNA-expressing donors and 29 non-PNA-expressing donors. The EBV genome was sought in the saliva and buccal cells of both types of donors. The targeted granules of cells from a PNA expressing donor were studied by electron-microscopy. The prevalence of anti-EBV antibodies was similar in RA patients with and without APF, whereas the APF positive sera was elevated in acute IM. The titres of anti-EBV antibodies did not correlate to the expression of PNA in the buccal cells of the donors. There was no relationship between this expression and the presence of the EBV genome in the material obtained from 'positive' donors, relative to 'negative' donors. No virus like particles could be detected inside the granules by electron microscopy. These results indicate that there are no direct relationships between EBV and the APF/PNA system, although APF was present in a number of patients with IM. PMID- 7980851 TI - Contribution of glutamate decarboxylase antibodies to the reactivity of islet cell cytoplasmic antibodies. AB - The contribution of glutamate decarboxylase (Mr 65000) antibodies to the reactivity of islet cell cytoplasmic antibodies with the 'whole' islet staining pattern from patients with newly diagnosed Type I diabetes was investigated. Diluted sera (n = 10) were preincubated with increasing concentrations of purified recombinant human islet glutamate decarboxylase (Mr 65000) and the change in islet cell cytoplasmic antibody binding was evaluated by quantitative immunocytochemistry. Binding to islet cells was partially blocked by glutamate decarboxylase in 9/10 diluted sera; the maximum blocking obtained at high concentrations of glutamate decarboxylase (5 micrograms/ml) was 36% (median, range 24-61%). In contrast, binding to islet cells in three diluted sera (two polyendocrine patients without Type I diabetes and one patient with newly diagnosed Type I diabetes) with the 'selective' islet staining pattern was totally blocked by glutamate decarboxylase. The concentration of glutamate decarboxylase required to achieve maximum blocking was less for the 'whole' islet (0.4-8.0 micrograms/microliters undiluted serum) compared to the 'selective' islet (20-645 micrograms/microliters undiluted serum) positive sera. All sera were positive for glutamate decarboxylase antibodies in an immunoprecipitation assay using 35S-methionine labelled extract of baby hamster kidney cells transfected with glutamate decarboxylase. However, the binding activity of these antibodies was less in the sera positive for the 'whole' islet compared to the 'selective' islet staining pattern. In conclusion, glutamate decarboxylase antibodies contribute partially to the reactivity of islet cell cytoplasmic antibodies of the 'whole' islet staining pattern in the sera of newly diagnosed patients with Type I diabetes, and totally to reactivity of the 'selective' islet staining pattern. The antigens recognized by the other antibodies contributing to the 'whole' islet reactivity remain to be defined. PMID- 7980852 TI - HLA-DQB1 associations with anti-topoisomerase-1 antibodies in patients with systemic sclerosis and their first degree relatives. United Kingdom Systemic Sclerosis Study Group. AB - The frequency and functional properties of anti-topoisomerase-1 antibodies (ATA) have been studied in 58 systemic sclerosis (SSc) probands, 218 first degree relatives and 22 spouses. The dependence of ATA on the presence of certain HLA DRB1 and HLA-DQB1 alleles was examined. ATA were detected by immunodiffusion, by absorption or inhibition of topoisomerase-1 enzymic activity, by immunoblotting of a K562 cell extract and by immunoprecipitation of 35S radiolabelled cell lines. HLA class II typing for HLA-DRB1 and HLA-DQB1 was performed by oligonucleotide typing in 49 families. Six probands and two relatives had ATA. The relatives with ATA had SSc. All eight individuals with ATA directly inhibited topoisomerase-1 function. Four of the eight had limited skin disease and four had diffuse skin involvement. The seven who were genotyped had at least one HLA-DQB1 allele encoding for tyrosine at position 30 of the first domain. Therefore, ATA are not widely dispersed within families, but rather are only present in those with SSc, and certain genetic requirements appear necessary for their generation. PMID- 7980853 TI - Immunoglobulin V region sequences of two human antiplatelet monoclonal autoantibodies derived from B cells of normal origin. AB - Autoimmune thrombocytopenia has been attributed to the presence of antiplatelet autoantibodies which mediate platelet destruction. The derivation of these autoantibodies is presently unknown. While normal B cells do not produce these autoantibodies in vivo, it has been demonstrated in vitro by somatic cell hybridization that the B lymphocytes of nonthrombocytopenic individuals have the potential to produce antiplatelet autoantibodies. Antigen specificities of these antibodies are similar to those seen in autoimmune thrombocytopenic purpura and the lupus anticoagulant syndrome. The immunoglobulin V region genes encoding two such human monoclonal antiplatelet antibodies, an anti-GP IIb (STO 171) and an anti-phospholipid antibody (STO 103) derived from tonsillar lymphocytes of a non thrombocytopenic male, have now been sequenced. These antiplatelet antibodies were found to be encoded by unmutated germline VH and VK genes. The third complementarity determining region (CDR3) of the genes encoding both of these antibodies have unique D regions with evidence of N-nucleotide additions, and the light chain genes show VK-JK junctional diversity. STO 103 is encoded by the VH4 V71-2 germline gene and a truncated JH4 gene. The light chain gene showed closest homology with the VK4 Humk18 gene and JK2 gene. STO 171 showed closest homology with the VH4.18 germline gene and had a complete germline JH6 gene. The light chain of STO 171 is encoded by the VK3 Humkv325 germline gene, which is also used by some rheumatoid factors and cold agglutinins, and a JK4 gene. Although these antibodies were not derived from circulating B cells or found to be actively producing antibody at the time they were harvested, it is possible that naturally occurring antibody producing B cells, similar to those represented here, are recruited for the development of pathogenic autoantibodies in immune thrombocytopenia. PMID- 7980854 TI - Anti-idiotypes against antiphospholipid antibodies are present in normal polyspecific immunoglobulins for therapeutic use. AB - In the present study we found that antiphospholipid activity in sera from patients with anticardiolipin antibodies was inhibited in vitro by therapeutic polyspecific normal immunoglobulins (IVIg). In fact, F(ab')2 fragments from IVIg (IVIg-F(ab')2) inhibited the binding of anticardiolipin antibodies to the corresponding antigen in a dose-dependent fashion, thus suggesting that the interaction between IVIg-F(ab')2 and anticardiolipin antibodies occurred within or near the antigen combining site. The maximal inhibition ranged from 35.25 +/- 5.56 to 64 +/- 5.48%. In addition, patients' IgG containing antiphospholipid activity specifically bound insolubilized IVIg-F(ab')2, as assessed by enzyme linked immunosorbent assay (ELISA). These results indicate that IVIg obtained from a large pool of normal donors contain anti-idiotypic antibodies directed against idiotypes located on antiphospholipid antibodies. Moreover, our observations suggest that the reported favourable effect of high dose infusion of IVIg in patients with recurrent abortions due to antiphospholipid antibodies may depend, at least in part on inhibition of the binding of such autoantibodies to the corresponding antigens (s) and/or inactivation of idiotype bearing B cell clones. PMID- 7980855 TI - [Herbalogical study of Chinese drug guijiu and xiaoyelian]. AB - Through a critical study of ancient Chinese herbals, it is concluded that the botanical origin of Guijiu should be Dysosma versipellis or D. pleiantha instead of Sinopodophyllum emodi, and that Xiaoyelian was originated from the latter. In Chinese Pharmacopoeia and many other books, the botanical origin of Xiaoyelian was erroneously referred to as Podophyllum emodi. PMID- 7980856 TI - [Comparisons of pharmacological effect and LD50 among four kinds of Hawthorn fruit]. AB - Four kinds of Hawthorn Fruit, namely Large Chinese Hawthorn, Chinese Hawthorn, Nippon Hawthorn and Yunnan Hawthorn, were compared in animal experiments. Their effects on small intestine motion, myocardial ischemia and hypercholesterolemia have been found different from each other. PMID- 7980857 TI - [Biological characteristics of Ligusticum chuanxiong Hort]. AB - Observational studies were conducted on the biological characteristics of Ligusticum chuanxiong, such as suitable growth environment, growing period, growth of stems, leaves and rhizomes, yield structure, etc. The specific regularities of each growth period were also studied. PMID- 7980858 TI - [Assay of the chemical composition in Chinese medicine Monetaria Moneta]. PMID- 7980859 TI - [Characterization and quantification of dermatan sulfate from donkey skin]. AB - Dermatan sulfate (DS), a recently known antithrombotic glycosaminoglycan, was isolated and purified from donkey skin. Physiochemical characteristics of the glycan, including constituent analysis, electrophoretic behaviour, molecular mass, specific lyase degradations, IR and PMR spectra were described, using porcine skin-origin dermatan sulfate as a standard reference. Contents of DS in donkey skin and its gelatinized preparations (Ejiao) were also measured. Results indicate that the presence of DS may explain the long reputed clinical efficacy of donkey skin and Ejiao in treating serious symptoms associated with what has been called endogenous wind in traditional Chinese medicine. PMID- 7980860 TI - [Optinum for extracting total alkaloids in Datura metel L]. PMID- 7980861 TI - [Compounds from Caesalpinia sappan L]. AB - Two compounds were isolated from the stem of Caesalpinia sappan. Their structures were elucidated on the basis of physical and spectral analysis. They were named as tetraacetylbrazilin and protosappanin A respectively. PMID- 7980862 TI - [Chemical constituents of Chinese medicinal plant Rubus parviforlius L]. AB - Two crystalline components were isolated from the roots of Rubus parviforlius and determined as niga-ichigoside F1 and sauvissimoside R1 by spectroscopic evidences and chemical reactions. They were obtained from the plant for the first time. PMID- 7980863 TI - [Chemical constituents of Cynanchum stauntonii (Decne.) Schltr. ex Levl]. PMID- 7980864 TI - [Observation on the action of extractum semen Persicae on anti-fibrosis of liver]. AB - It was observed that Extractum Semen Persicae acted obviously on hepatic fibrosis induced by CCl4. Through promoting the degradation of collagens type I, II, IV, VI and fibronectin, ESP has proved helpful in markedly reducing the fibrous septa composed of both collagenous and reticular fibers as well as in repairing the structure of hepatic tissues. PMID- 7980865 TI - [Animal experiments on meridian-reaching actions of traditional Chinese medicinal herbs]. AB - With the level variations of cAMP and cGMP in cat tissues as the criteria, the meridian actions reaching of Fructus Schisandrae, Radix Stephaniae Tetrandrae and Herba Houttuyniae were studied tentatively in animal experiments. The result obtained in this way approximates to the understanding of the meridian reaching actions of Chinese medicinal herbs as approved by traditional Chinese medicine. PMID- 7980866 TI - [Progress in the study on fructus Ligustri lucidi]. PMID- 7980867 TI - Kinetic analysis of the opened bicyclic enzyme cascades. AB - A kinetic analysis of the opened bicyclic enzyme cascade is presented. It includes the time-dependence of the concentrations of the modified and unmodified forms of the interconvertible enzymes, as well as their fractional modifications, from the onset of the reaction to its completion. The transient phase equations obtained allow the definition of new regulatory properties. The expressions corresponding to the concentrations and fractional modification in the steady state are derived as particular cases of the general transient phase equations. These steady-state expressions agree with those obtained by other authors. PMID- 7980868 TI - Semisynthetic insulin analogues modified in positions B24, B25 and B29. AB - New semisynthetic analogues of human insulin, modified in the C-terminal region of the B-chain, were prepared to refine our understanding of the importance of particular amino acid residues in the expression of hormone biological properties. The following insulin analogues were synthesized by trypsin-catalyzed peptide-bond formation between the C-terminal arginineB22 of des-octapeptide(B23 B30)-insulin and synthetic octapeptides with the epsilon-amino group of lysineB29 protected by a phenylacetyl group: [L-Lys(Pac)B29]insulin, [D-PheB24,B25,L Lys(Pac)B29]insulin and [D-Phe(p-Et)B24, L-Lys(Pac)B29]insulin. Enzymatic deprotection using immobilized penicillin amidohydrolase yielded: human insulin, [D-PheB24,B25]insulin and [DPhe(p-Et)B24]-insulin. Biological in vitro potencies (specific binding to cultured human lymphocytes IM-9 and lipogenic potency in isolated rat adipocytes) of the semisynthetic analogues were estimated, ranging from 0.2 to 100% relative to porcine insulin. PMID- 7980869 TI - Primary structure of CC-III, the glycosylated cysteine proteinase from the latex of Carica candamarcensis Hook. AB - The amino acid sequence of the cysteine proteinase CC-III from the latex of the subtropical species Carica candamarcensis Hook has been determined with the exception of seven residues (pos. 180-186). It was deduced from the sequence analysis of the whole chain and peptides obtained by tryptic, chymotryptic, peptic and thermolysinolytic hydrolysis. CC-III consists of 214 amino acid residues. Out of a total of eight cysteine residues, six are located at positions involved in the formation of the three disulfide bridges stabilizing the structure of papain related enzymes. CC-III from Carica candamarcensis is a glycoprotein with the carbohydrate moiety bound to asparagine at position 44. Out of 210 residues compared with the sequences of the four cysteine proteinases of Carica papaya L., CC-III shares 125 identical ones (59.5%) with papain, 142 (67.6%) with papaya proteinase IV, 146 (69.5%) with papaya proteinase III and 156 (74.3%) with chymopapain. All amino acid residues constituting the active site and subsite S2 in chymopapain are conserved in CC-III with the exception of the substitution Leu157--> Val in the latter. This fact as well as the highest degree of identity between CC-III and chymopapain point to a similar specificity of both enzymes and thus CC-III might be a suitable substitute for chymopapain as a chemonucleolytic agent. PMID- 7980870 TI - Fatty acid binding of myoglobin depends on its oxygenation. AB - In the present work we show with different binding assays chicken gizzard myoglobin is able to bind fatty acids and bromosulphophthalein (BSP) in vitro. The fatty acid binding depends on the oxygenation of the myoglobin. Freshly prepared chicken gizzard, chicken or bovine heart myoglobin have a high fatty acid binding capability. However, when oxy-myoglobin in converted to met myoglobin by dialysis against acidic buffer at high ionic strength (or when commercially available myoglobins are used) a 60-70% lower fatty acid binding capacity is found. Like bovine serum albumin (BSA), gizzard myoglobin has the highest affinity for unsaturated fatty acids and a lower affinity for saturated fatty acids or dyes. Chicken gizzard smooth muscle myoglobin may function as an additional fatty acid binding protein in vivo. PMID- 7980871 TI - Migration inhibitory factor-binding sarcolectin from human placenta is indistinguishable from a subfraction of human serum albumin. AB - Human sarcolectin is known as growth promoter and interferon-alpha/beta antagonist. Besides N-acetylneuraminic acid-dependent cell agglutination it also binds to a macrophage migration inhibitory factor (MIF). Several types of negatively charged carbohydrates interfere with this binding, indicating importance of a negatively charged cluster. Since human serum albumin that has very similar properties in gel electrophoretic analysis can also bind to this factor with a comparatively reduced extent, sarcolectin and albumin are compared biochemically and immunologically. Their peptide maps, generated by cleavage with cyanogen bromide and N-chlorosuccinimide, reveal no differences. The N-terminal sequences are identical up to the fourteenth position that have unequivocally been determined. Reactivities to anti-human serum albumin antibody that inhibits binding of sarcolectin to MIF are similar. Fractionation of human albumin by chromatography on hydroxyapatite yields a subfraction with increased specific activity, measured by extent of inhibition of sarcolectin-MIF interaction. It exhibits the same inhibitory capacity as a similarly derived subfraction from sarcolectin. Interestingly, rabbit and pig serum albumins are as active as human albumin to inhibit binding of sarcolectin to MIF, whereas hamster, mouse, horse and bovine albumin preparations were ineffective up to 2.5 mg/ml. Thus, sarcolectin appears to be a subfraction of human serum albumin whose functionally relevant molecular peculiarities are presently unknown. Neither treatment with organic solvents nor with lipases, but exposure to trypsin, chymotrypsin and pronase can impair sarcolectin's ability to bind MIF. PMID- 7980872 TI - Antibodies from egg yolk of immunized hens against a bioactive caseinopeptide (beta-casokinin-10). AB - Antibodies (IgY) directed against a synthetic, bioactive peptide (beta-casokinin 10) were obtained from egg yolk of immunized chickens. Using a beta-casokinin 10/BSA conjugate for immunization, large quantities of high-titered anti-peptide antibodies were obtained. ELISA standard curves for beta-casokinin-10 were linear in the range 30-22,000 ng/ml. IgY-antibodies against beta-casokinin-10 recognized not only the immunogenic peptide structure but also analogues epitopes in protein preparations containing bovine beta- and alpha s-caseins, respectively, as well as in ovine caseins. The anti-beta-casokinin-10 IgY-antibodies are intended to be used as immunochemical reagents in future structure-activity studies of bioactive casokinins that are inhibitors of the angiotensin-converting enzyme. PMID- 7980873 TI - Biological activity of the Escherichia coli lipoprotein: detection of novel lymphocyte activating peptide segments of the molecule and their conformational characterization. AB - The lipoprotein (LP) from Escherichia coli and other Enterobacteriaceae as well as lipoprotein derived lipopeptides constitute potent B lymphocyte mitogens. Several synthetic peptide segments of the lipoprotein were tested for mitogenic activity towards splenocytes of BALB/c mice. Mitogenic effects were observed for the lipoprotein fragments LP-(2-15), LP-(2-20), LP-(2-25), and LP-(33-47), and a less pronounced effect was determined for LP-(2-10). The mitogenicity of the peptides could be further enhanced by their attachment to the lipopeptide N palmitoyl-S-[2,3-bis(palmitoyloxy)-(2R,S)-propyl]-(R)- cysteine (Pam3Cys). The additional insertion of 6-aminohexanoic acid (Ahx) between the peptide segments and Pam3Cys further increased mitogenicity. Thus, in addition to the known mitogenic N-terminal lipopeptide of lipoprotein, additional peptide segments of the molecule were shown to exhibit a biological activity. PMID- 7980874 TI - Expression of biologically active monomeric form of human M-CSF in baculovirus infected silkworm, Bombyx mori. AB - The human macrophage colony stimulating factor (hM-CSF) in its monomeric form has been over-produced in BmN cells and in silkworm larvae infected with the recombinant baculovirus Bm284M-CSF. The recombinant monomeric M-CSF (rhM-CSF) exhibited the activity of 8-14 x 10(4) units/ml of cell culture medium. When the insect larvae were infected with the recombinant virus, the maximum rhM-CSF was expressed 4-5 days post infection with an activity of 3 x 10(6) units/ml hemolymph. The monomeric rhM-CSF was purified to homogeneity through three steps of purification. A pilot purification yielded 1 mg of homogeneous monomeric rhM CSF from 10 larvae. The purified rhM-CSF monomers gradually dimerized in vitro. In contrast, the crude or the semi-purified monomers did not dimerize in vitro, indicating that the presence of an unknown moiety in the rhM-CSF preparations obtained from hemolymph interfered with dimerization. PMID- 7980875 TI - Immunorecognition of ring skeleton of taxanes by chicken egg yolk antibodies. AB - Anti-10 deacetylbaccatin III (DAB) antibodies (IgY) were elicited in hens immunized with a succinyl-DAB/BSA conjugate and extracted from egg yolk. As shown by indirect competitive inhibition enzyme immunoassay (CIEIA), the addition of free-DAB competitively inhibited the binding of affinity purified anti-DAB IgY to DAB/BSA solid phase conjugated antigen. The assay enabled the detection of DAB in concentrations as low as 7.5ng/ml (13.7 nM DAB), whereas anti-DAB IgY did not react with taxol even at a concentration a thousand times higher. The structural requirements of the diterpenoid nucleus for binding to IgY were considered on the basis of the levels of cross-reaction found with 10 authentic taxanes. The results indicate that anti-DAB IgY represents the first high affinity antibody produced capable of recognizing the ring skeleton of taxol precursors. PMID- 7980876 TI - Identification of ommin in the integument of the silkworm, Bombyx mori. AB - An ommin was isolated from the integument of the quail mutant of the silkworm, Bombyx mori, using column chromatography on SP-Sephadex and cellulose powder. As a standard, ommin was isolated from diapause eggs of the normal silkworm. The red pigment from the larval integument of quail mutants was identical to the standard compound with respect to absorption spectrum, infrared spectrum and RF values in thin-layer chromatography (TLC). After acid hydrolysis of the pigment, 3 hydroxykynurenine was detected by TLC. This is the first report of an ommin in a lepidopteran larval integument. PMID- 7980877 TI - Critical care nurses' and doctors' attitudes to parasuicide patients. AB - The aim of this study was to investigate the attitudes of critical care nurses and doctors to parasuicide patients. A survey was conducted of 299 nurses and 81 doctors working in emergency departments and intensive care units of nine Victorian hospitals. Data obtained from responses to a Likert-type questionnaire were assessed in order to explore relationships between the doctors' and nurses' attitudes and demographic and other variables. The survey showed that the nurses' and doctors' attitudes to parasuicide patients were generally negative and that respondents did not enjoy caring for parasuicide patients. Nurses were significantly more likely than doctors to think that nurses' attitudes to parasuicide patients were poor. Nurses were also significantly more likely than doctors to self report that they were afraid of saying the wrong thing to these patients. Eighty three percent of nurses and 61% of doctors stated that they would benefit from suicide related education. Addressing this expressed need must be a high a priority for critical care units if parasuicide patients are to receive more individual and appropriate care and if their carers are to experience greater work satisfaction. PMID- 7980878 TI - Clinical research and the culture of collaboration. AB - This article aims to share some of the strategies and principles that facilitated the completion of an experimental research project undertaken at the Liverpool Health Service (formerly Liverpool Hospital) in the South West of Sydney. The experience demonstrated the interdependence of the academic and clinical nurse practitioners undertaking the project. A collaborative approach to nursing research in which complementarity of participants is recognised and valued is recommended. PMID- 7980879 TI - Where does all the data go? PMID- 7980880 TI - The best and the worst: students' experiences of clinical education. AB - This paper reports on a component of a research project that was designed to identify the attributes of clinical settings which support learning. Thirty final semester nursing students were interviewed and asked to describe their best clinical learning experience. Students valued positive relations with ward staff and appreciated recognition for their contribution to patient care. The need to belong and be accepted by the ward staff was a common theme throughout all the interviews. Students enjoyed being busy and having an appropriate level of autonomy but found this difficult to achieve unless their role as students was clear to ward staff. The clinical lecturers' role appeared to be one of facilitation rather than instruction. The findings emphasise the importance of the culture of the workplace in determining the success of the learning experience. Implications for clinical education and directions for future research are discussed. PMID- 7980881 TI - Conversations with researchers. 2. Helen Baker, research fellow, Deakin University, talks to Robyn Parkes. Interview by Robyn Parkes. PMID- 7980882 TI - A comparative study of neonates' umbilical cord management . AB - The aim of this study was to establish the effect of treating neonates' umbilical cords with chlorhexidine 0.5% in alcohol 70% on cord separation time and to observe the clinical and microbiological consequences of not treating the cords of healthy neonates. The treated group contained 466 babies whose cords were treated with chlorhexidine, 424 babies were not treated. Microbiological colonisation patterns of the cords of babies in both groups were monitored both for purposes of this investigation and to ensure that no untoward consequences resulted from non-treatment. The research showed that treatment prolonged separation time by 1.7 days, which was significant at the level of p = 0.000, and that normal colonisation was delayed in the treated group. PMID- 7980883 TI - How effectively do we use double staff time? AB - This paper describes a group of registered nurses' investigation of the use of 'double staff time' in a neonatal unit. Using participatory action research, the nurses explored why it was difficult for the unit's staff to take part in continuing education programs that were provided during double staff time. The group drew on their personal experiences as well as data collected from peers in the neonatal unit. The data illustrated that nursing activities and nursing handovers were two factors that encroached on nurses' professional development time. PMID- 7980884 TI - Domiciliary detoxification: a cost effective alternative to inpatient treatment. AB - In this study, 20 subjects who had home detoxification with supervision and support from the Western Australian Alcohol and Drug Authority Community Nursing Service were matched with 20 subjects who had inpatient detoxification in the Authority's detoxification facility. Subjects were interviewed between nine and 22 months (mean 15.5 months) after detoxification to compare client outcomes and the costs of home and inpatient detoxification. The results indicate that, for suitable clients, home detoxification was at least as beneficial as inpatient detoxification and that it was achieved at a much lower cost than inpatient care. PMID- 7980885 TI - The incidence of postnatal depression in a rural area and the needs of affected women. AB - The Gippsland Maternal and Child Health Service Research Group conducted a survey to investigate the incidence of postnatal depression in women with three months old infants who were born in the Gippsland region. As well, the mothers were asked how they could have been better supported in the five to 13 weeks after their babies were born. The respondents' Edinburgh Postnatal Depression Scale scores indicated that 58% of women had experienced depression. These women expressed a need and a preference for home based support, i.e. occasional child care, extended home help, greater access to telephone counselling and home visits by maternal and child health nurses and for education of their infants' fathers. On the basis of the study and their experiences, the Research Group makes recommendations about how the needs of women with postnatal depression may be better met. PMID- 7980886 TI - Preparing students for their patients' deaths. AB - The purpose of the present study was to examine the preparation that Australian undergraduate nursing students receive for their patients' deaths. A survey of the curricula of undergraduate nursing degree programs in Australian universities was undertaken to determine the amount of time devoted to death education and the pedagogical methods used in these programs. Of particular interest was the amount of time spent on students' reactions to death and the coping strategies that they might find helpful in these situations. The results revealed considerable variation in the time spent on death education (range 5-192 hours) in the 28 undergraduate nursing degree programs on which information was received. A mean time of 44 hours was reported with 4.5 hours spent on nurses' reactions to death and loss and instruction in debriefing strategies. The favoured pedagogical method was problem-solving in clinical experience. The implications of this study for nursing practice are discussed. PMID- 7980887 TI - Mother-infant interactions in postpartum depression: an early intervention program. AB - This paper examines the role of postnatal intervention in the prevention of the negative consequences of postpartum depression on developing mother-infant relationships. It is argued that, once difficulties in these interactions have been identified, direct attempts to modify the interactions must occur within a framework that includes maternal, paternal, partnership/marital and social variables. An intervention program that may be instituted by nurses is described. The Baby Happiness, Understanding, Giving and Sharing (HUGS) Programme is an attempt to integrate direct intervention in mother-infant interactions into a systemic framework which takes into account contextual variables such as cognitive style and social support. PMID- 7980888 TI - Mentoring for career success and satisfaction. PMID- 7980889 TI - Conversations with researchers. 3. Jeanette Robertson, nurse researcherat Princess Margaret Hospital for Children, Perth, talks to Natalie Newman. Interview by Natalie Newman. PMID- 7980890 TI - Is there enough mentoring in nursing? AB - This paper examines the debate about the benefits of mentoring in nursing and argues that the evidence indicates that mentoring is a professional behaviour that contributes to career success and the development of professional leaders. Some strategies to facilitate mentoring are suggested. As well, the paper presents the findings from analysis of four studies which provided data on the incidence of mentoring among 317 nursing unit managers, 368 clinical nurse specialists, 478 RNs entering a graduate course and 235 of the latter group on completion of their course. The results show that, of those who reported their mentoring experience, more unit managers (45%) than clinical specialists (35%) experiencing mentoring and that 79% of graduating RNs reported that they had increased their mentoring of others since beginning their course. The overall incidence of mentoring was lower than that reported in the United States. Reasons for the findings are discussed. PMID- 7980891 TI - Optical sensors in medicine. Joint meeting of MSSIG (The Diagnostics Club) and OSCA, UMIST, 22nd June 1994. PMID- 7980892 TI - An in situ electrosynthesized amperometric biosensor based on lactate oxidase immobilized in a poly-o-phenylenediamine film: determination of lactate in serum by flow injection analysis. AB - The electrochemical immobilization of lactate oxidase in a poly-o phenylenediamine film permits the one-step and all-chemical construction of a lactate amperometric biosensor. The sensor was prepared in situ i.e. in the flow injection analysis (FIA) system by simply injecting a plug of a solution containing the monomer and the enzyme. At a flow rate of 50 microL/min linearity was observed up to 0.2 mM lactate and detection limits of about 2 microM could be easily achieved. Faradaic interferences caused by ascorbate, urate, cysteine and acetaminophen were sufficiently minimized to permit lactate determination in diluted serum by FIA. Results obtained by FIA-amperometric detection compared well (according to a proper t-test at a 95% confidence level) with those obtained by a standard enzymatic colorimetric assay. At a flow rate of 1 ml/min a sample throughput higher than 70 sample h-1 was achieved. After one week of continuous use in the FIA system a 75% decrease in biosensor sensitivity was observed. PMID- 7980893 TI - Comprehensive management of bilateral acoustic neuromas. Current perspectives. AB - Bilateral acoustic neuromas are pathognomonic for neurofibromatosis 2. Patients with neurofibromatosis 2 present complex and challenging management problems, because growth or surgical removal of the acoustic neuroma may result in total hearing loss. Early diagnosis with gadolinium-enhanced magnetic resonance imaging and refinements in hearing preservation surgery have improved our ability to prevent total hearing loss. For patients with larger tumors or no useful hearing, the auditory brain-stem implant allows restoration of some auditory function when the tumor is removed. We describe our management strategy for patients with bilateral acoustic neuromas, and present case reports to show their diversity. We also discuss the newly identified neurofibromatosis 2 tumor suppressor gene. PMID- 7980894 TI - Microbiology and management of chronic maxillary sinusitis. AB - OBJECTIVE: Assessment of the microbiology and management of patients who suffered from chronic maxillary sinusitis was studied retrospectively. DESIGN: Retrospective analysis of microbiology and antimicrobial therapy of 68 patients who underwent the Caldwell-Luc procedure for chronic sinusitis had not received antimicrobials before surgery and whose cultures showed bacterial growth. SETTING: This study was performed at the Naval Hospital in Bethesda, Md. INTERVENTION: Amoxicillin-clavulanic acid was given to 18 patients, amoxicillin or ampicillin to 25, cefaclor to 17, and erythromycin to eight. RESULTS: A total of 183 isolates (123 anaerobic and 60 aerobic) were recovered. Anaerobic organisms only were recovered from 35 (51%), specimens, and aerobic or facultative bacteria only in 12 (18%), and mixed aerobic and anaerobic flora in 21 (31%). Thirty-four aerobic and anaerobic beta-lactamase-producing bacteria were isolated from 28 patients. The 18 patients who received amoxicillin clavulanic acid had the most rapid and complete response to therapy, none required a change in therapy, and surgical drainage was required in one case. Of 25 patients who received amoxicillin or ampicillin, eight required a change of therapy due to clinical failure (32%), including three who also had surgical drainage. Of 17 that received cefaclor, five had an antibiotic change (29%), one with surgical drainage. Of the eight who were treated with erythromycin, three needed antibiotic change (38%), two with surgical drainage. Resistant organisms were recovered from most of the patients that required therapeutic change. CONCLUSIONS: These findings indicate the major role of aerobic and anaerobic beta lactamase-producing bacteria organisms in the polymicrobial etiology of chronic maxillary sinusitis and illustrate the superiority of therapy effective against these bacteria. PMID- 7980896 TI - A clinical study of human type IV collagen as tympanic membrane grafting material. Preliminary noncomparative study. AB - OBJECTIVE: To evaluate tolerance for this middle-ear implant and its effectiveness in eardrum healing under various pathologic conditions. SETTING: A 12- to 18-month follow-up case series at an institutional referral center offering hospitalized care. PATIENTS: Twenty-six eligible volunteers suffering from tympanic perforation or tympanic pocket retraction class II and III in Tos' classification. INTERVENTION: Patients underwent implantation with the type IV collagen film (film called "MTY" from the French membrane tympanique). The surgical procedure was similar to those using the temporal aponeurosis or the tragal perichondrium. OUTCOME MEASURE: Anatomic criteria was determined by otoscopy, and functional audiometric criteria was determined by air-borne gap measurements and by effects on cochlear function. RESULTS: Twenty-two of 26 patients were completely healed after 6 months, with no subsequent evolution. Nineteen of 26 subjects underwent a 1-year postoperative audiometric follow-up examination: 13 (68%) had an air-borne gap less than 10 dB, four (21%) had between 11 and 20 dB, and two (11%) had between 21 and 30 dB. Adverse effects included one patient whose MTY fell into the middle ear, three patients with transient myringitis, and one patient with otitis media with effusion. CONCLUSIONS: A human type IV collagen film may be a possible alternative to autologous tissue in tympanic membrane reconstruction. This new biomaterial was tested on patients with various diseases common in clinical otology, and demonstrated a good biocompatibility of MTY in the different pathologic conditions of chronic otitis media. A future randomized, controlled trial will randomly allocate patients to receive either MTY collagen film or tissue from the temporal aponeurosis. PMID- 7980895 TI - The human communicating nerve. An extension of the external superior laryngeal nerve that innervates the vocal cord. AB - OBJECTIVE: A second source of motor innervation for the thyroarytenoid (TA) muscle, other than the recurrent laryngeal nerve, has been suggested by clinical and experimental observations. Early anatomists noted what appeared to be small nerves connecting the cricothyroid and TA muscles; however, these observations were disputed by later anatomists and subsequently forgotten. METHOD: In this study, we processed 27 human hemilarynges with Sihler's stain, a technique that clears soft tissue and counterstains nerve. In addition, four communicating nerves (CNs) were frozen sectioned and stained for acetylcholinesterase, a marker for motor neurons. RESULTS: In 12 (44%) of the 27 specimens, a neural connection was found that exited the medial surface of the cricothyroid muscle and then entered into the lateral surface of the TA muscle. In general, this CN was composed of two parts: an intramuscular branch usually combined with the recurrent laryngeal nerve or terminated within the TA muscle directly and an extramuscular branch that passed through the TA muscle and terminated in the subglottic mucosa and around the cricoarytenoid joint. All four CNs tested positive for acetylcholinesterase. Specifically, the CNs contained an average of 2510 myelinated axons, of which 785 (31%) were motor neurons. CONCLUSION: The results suggest that when the CN is present, it supplies a second source of motor innervation to the TA muscle and extensive sensory innervation to the subglottic area and cricoarytenoid joint. In addition, the CN may be the nerve of the fifth branchial arch, a structure that has never been identified (to our knowledge). PMID- 7980898 TI - Unilateral mimicking bilateral benign paroxysmal positioning vertigo. AB - BACKGROUND: Unilateral benign paroxysmal positioning vertigo (BPPV) may mimic bilateral BPPV if the diagnostic positioning maneuver is executed without appropriate alignment of the head and neck with the trunk. OBSERVATIONS: Appropriate alignment is achieved by adjusting the plane of the affected posterior semicircular canal so that it is parallel to the plane of diagnostic head tilt, ie, 45 degrees horizontal head rotation to the left before a head tilt to the right in suspected right-sided BPPV. With inappropriate head alignment and head tilt to the side of the unaffected ear, a free-floating clot within the long arm of the uppermost posterior canal may gravitate toward the cupula and become settled on it. This causes ampullopetal cupulolithiasis, evoking geotropic nystagmus, which may mimic BPPV of the unaffected ear. CONCLUSION: This hypothesis explains the seemingly paradoxical observation of immediate relief from "bilateral BPPV" following unilateral surgical canal occlusion on the "more symptomatic" side. PMID- 7980897 TI - Cystic acoustic neuromas. Results of translabyrinthine surgery. AB - OBJECTIVE: This study was designed to investigate the surgical outcome of translabyrinthine surgery of cystic acoustic neuromas. DESIGN: Prospective registration of audiovestibular, otoneurologic, and neuroradiologic data of all patients operated on for cystic neuromas in the period 1976 to 1992. The diagnosis was proposed by neuroradiologic investigation, confirmed at surgery, and verified histologically. Clinical follow-up was performed 1 year after surgery. SETTING: The study included all patients with cystic acoustic neuromas from the entire country, referred to the centralized otoneurosurgical team in the Department of Otorhinolaryngology-Head and Neck Surgery, Gentofte University Hospital, and Department of Neurosurgery, Rigshospitalet, University of Copenhagen, Denmark. PATIENTS: The study included 23 patients (11 female and 12 male). Ages ranged between 23 and 77 years with a median of 51.2 years. MAIN OUTCOME: Our hypothesis suggested that surgical outcome of cystic acoustic neuromas was poorer compared with noncystic acoustic neuromas of matching size. The results of this study seem to confirm the hypothesis. RESULTS: The results are rather poor compared with results achieved in surgery of noncystic tumors of matching size, particularly the poor postoperative facial nerve function. CONCLUSIONS: Even though the operation for a cystic acoustic neuroma may appear to be easier and faster than the operation for a solid tumor, there is a high risk for accidental lesion of the facial nerve, in spite of using facial nerve monitoring. Rapid symptomatic worsening may occur due to sudden expansion of cystic elements and, therefore, a wait-and-see policy should not be applied to patients with cystic tumors. PMID- 7980900 TI - Endoscopic transseptal vidian neurectomy. AB - OBJECTIVE: Evaluation of the endoscopic transseptal approach of vidian neurectomy. DESIGN: A case series, with a follow-up of 12 to 24 months. SETTING: A referral center. PATIENTS: A consecutive sample of 11 adult patients with resistant vasomotor rhinitis: eight with severe rhinorrhea and three with recurrent nasal polyposis. All patients had a negative history of allergy and negative skin tests. All patients completed the study. INTERVENTION: The rigid nasal endoscope was used through a transseptal approach to reach the sphenopalatine foramen and to cut the vidian nerve. MAIN OUTCOME MEASURES: Intraoperative identification and cutting of the vidian nerve under direct endoscopic vision. Postoperative evaluation of rhinorrhea, sneezing, and recurrent disease. RESULTS: The vidian nerve was identified and sectioned bilaterally in all cases. Immediate and complete cessation of rhinorrhea uniformly occurred. Paroxysms of sneezing were vastly reduced. No recurrence was detected, except in one case. Three patients complained of dry eyes, but they had symptomatic relief with artificial teardrops. CONCLUSION: The technique of endoscopic transseptal vidian neurectomy is a minor surgical procedure with high efficacy and minimal postoperative morbidity. More cases and longer follow-up are necessary to provide long-term results. PMID- 7980899 TI - Acute Streptococcus pneumoniae meningogenic labyrinthitis. An experimental guinea pig model and literature review. AB - OBJECTIVE: To create an experimental model of Streptococcus pneumoniae type 3 meningogenic labyrinthitis (a leading cause of deafness) similar to that in human disease. DESIGN: Cohort analytic study of guinea pigs that were inoculated intrathecally with varying dilutions of S pneumoniae type 3; the progress of the disease was compared with that in saline solution-inoculated control animals. SUBJECTS: Healthy adult Hartley guinea pigs without clinical evidence of middle ear disease that were conveniently sampled. INTERVENTIONS: Intrathecal inoculation of 10(4) to 10(6) colony-forming units of S pneumoniae type 3 into 13 guinea pigs; signs and symptoms of meningitis/labyrinthitis were observed for 15 days and compared with those in two saline solution-inoculated control animals. MAIN OUTCOME MEASURES: Morbidity--labyrinthitis, meningitis; end point--death. RESULTS: The 10(4) to 10(6) colony-forming units of S pneumoniae type 3 caused inflammation that extended from the meninges to the inner ear via the cochlear aqueduct within 3 days after inoculation; a dose of 10(7) killed animals within 12 hours after inoculation. Three of five animals that were inoculated with a 10(6) dose died 3 days after inoculation; two of three animals that were inoculated with a 10(5) dose lived to 15 days after inoculation. One of two animals that were inoculated with a 10(4) dose did not become infected. Inflammation extended to the middle ear by round-window destruction. Reactive bone formation simulated labyrinthine osteosclerosis. Observers assessed histologic slides "blindly." CONCLUSION: Guinea pigs can survive 15 days after intrathecal inoculation of a 10(5) dose, with morphologic features similar to those in human disease. This is an effective model for this study of meningogenic labyrinthitis. PMID- 7980901 TI - Photodynamic therapy using m-tetra(hydroxyphenyl) chlorin. An animal model. AB - OBJECTIVE: To evaluate the potent photosensitizer m-tetra (hydroxyphenyl) chlorin (m-THPC) by using rabbits with cottontail rabbit papillomavirus-induced tumors and the canine larynx as model systems. DESIGN: Nonrandomized control trial. SETTING: Division of ear, nose, and throat research at a tertiary care teaching hospital. MATERIALS: Rabbits were used for relative retention ratio studies and tissue tolerance tests. Studies on the swelling of normal tissues in the larynx after photoactivation were done with canines. INTERVENTION: Animals were injected with 0.3 mg/kg of m-THPC. At varying intervals, tissues were exposed to 652 nm of light. OUTCOME MEASURES: Outcome measures consisted of four elements: (1) decay of plasma concentration over time, (2) interval to and duration of maximal ratio between drug concentration in normal tissue and tumor, (3) maximal permissible light exposure to normal tissue (skin and laryngeal mucosa) at an optimal interval, and (4) efficacy--number of tumors with partial and complete response. RESULTS: The largest papilloma to skin ratio (10:1) occurred 4 to 8 days after drug injection. The rabbit skin damage threshold was 40 to 60 J/cm2 at 6 days. The canine laryngeal edema and erythema thresholds were 50 to 70 J. A 75% cure rate of papillomas was achieved with tumors that were less than 100 mm2 in area at light doses that ranged from 25 to 75 J/cm2. CONCLUSIONS: m-THPC shows efficacy in treating papilloma virus-induced tumors. We present a protocol for rapid optimization of the factors required for tumor destruction with minimal normal tissue damage, thus permitting determination of an optimal therapeutic protocol for any photosensitizer. PMID- 7980902 TI - Tracheoplasty for congenital complete tracheal rings. AB - OBJECTIVE: To better appreciate the complex nature of the pediatric patient with tracheal stenosis due to congenital complete tracheal rings, we evaluated clinical presentation, methods of evaluation, necessity for surgical repair, associated anomalies, and outcome. DESIGN: Retrospective study. PATIENTS: Eighteen patients with long-segment tracheal stenosis due to congenital complete tracheal rings were evaluated at Cincinnati (Ohio) Children's Hospital Medical Center between 1985 and 1991. Three patients did not require surgical intervention. Fifteen patients underwent tracheoplasty with cardiopulmonary bypass through a midline sternotomy. RESULTS: The patients with congenital complete tracheal rings usually present with respiratory compromise in the first year of life. In the majority of patients, a diagnosis was made based on the symptoms and findings of an endoscopic examination with the aid of plain film roentgenography. In selected patients, computed tomography or magnetic resonance imaging was used. We evaluated symptoms, length of stenosis, type of repair, duration of intubation, and complications, as well as the mortality associated with this procedure. CONCLUSIONS: The technique of tracheoplasty has evolved at our institution, including the use of a posterior tracheal division, anterior castellated division, autologous pericardial patch grafting, and cricoid split with intubation for 7 to 21 days. We found the mortality associated with this procedure quite high at 47%, compared with previously published reports with mortality figures between zero and 77%. PMID- 7980903 TI - Primary head and neck cancer. Histopathologic predictors of recurrence after neck dissection in patients with lymph node involvement. AB - OBJECTIVE: Retrospectively analyze several histopathologic variables that may predict neck recurrence after neck dissection. DESIGN: From 1970 through 1980, 284 patients with pathologically confirmed metastatic squamous cell carcinoma underwent neck dissection and received no adjuvant therapy. Kaplan-Meier evaluation estimated a 74% 2-year neck recurrence-free rate. After adjusting for the standard covariates of age, gender, neck stage, and tumor grade, we also controlled for the time-dependent covariates of primary recurrence, occurrence in the side of the neck not operated on, or development of new head and neck primary disease. SETTING: A large referral-based practice. RESULTS: The number of lymph nodes involved, invasion of vascular/lymphatic space, invasion of soft tissue, and desmoplastic lymph node pattern adversely affect neck recurrence. A desmoplastic stromal pattern was associated with almost a sevenfold increased risk of neck recurrence. To our knowledge, this finding has not been reported previously. CONCLUSION: Histopathologic evaluation of metastatically involved cervical nodes can identify patients with head and neck cancer who are at high risk for recurrence. PMID- 7980904 TI - Treatment of patients with carcinoma of the thyroid invading the airway. AB - OBJECTIVE: To determine if complete resection (vs incomplete resection) improved survival of patients with thyroid carcinoma invading the airway. DESIGN: Retrospective, nonrandomized end point study. SETTING: Tertiary care referral centers. PATIENTS: All patients who had invasion of the airway by thyroid carcinoma and underwent some type of surgical resection. INTERVENTIONS: Surgical resection. MAIN OUTCOME MEASURE: Survival. RESULTS: Complete resection showed significantly better survival than incomplete resection (P = .0136). CONCLUSION: Complete resection of thyroid carcinoma invading the airway offers improved survival compared with incomplete resection. PMID- 7980905 TI - Functional compartments of the tensor veli palatini muscle. AB - OBJECTIVE: To evaluate a dual role for the tensor veli palatini muscle in tubal and palatal function. MATERIALS AND METHODS: The eustachian tube region of guinea pigs and macaques was fixed and processed for analysis by serial section histologic examination, micro-dissection, or both. The attachment, fiber direction, and regional relations of potentially discrete functional compartments in eustachian tube muscles were noted. RESULTS: The tensor veli palatini muscle in macaques has two anatomic sub-bellies. One appears to be a tubal dilator, the other to make the tube rigid along its longitudinal axis. No other muscle is directly associated with the eustachian tube in macaques. The tensor veli palatini muscle in guinea pigs has one gross belly that may affect palatal tensing and tubal dilation, rigidification, and stabilization. Other muscles of the eustachian tube in guinea pigs are a medial sub-belly of the medial pterygoid muscle, not previously described, and the levator veli palatini muscle. CONCLUSIONS: The muscular elements underlying tubal-palatal function in guinea pigs are more distinct and spatially separated than in macaques or humans. These differences may explain the confusion about the role of accessory muscles in tubal function. Muscular compartments of the eustachian tube complex in guinea pigs are easily accessible, which facilitates a more discrete and confident placement of electromyography electrodes. The guinea pig may be a useful model to better understand the interaction of multilevel compartmentalized physiologic sequences that underlie coordination of swallowing, breathing, and middle ear aeration. PMID- 7980907 TI - Prevention of sinus tympani retraction following tympanoplasty. How I do it. AB - Tympanoplasty for sinus tympani retraction may result in delayed recurrence of the original problem. This is especially true in children with marginal eustachian tube function. Autogenous tragal cartilage, scored on one surface with perichondrium attached on the other, produces a "natural bend" in the cartilage. When placed in the middle ear, with the scored convex surface facing the promontory, retraction into the sinus tympani can be prevented. This simple, yet effective, surgical technique is outlined. PMID- 7980906 TI - Solitary plasmacytoma of the mastoid bone presenting as coalescent mastoiditis. AB - Acute mastoiditis is a complication of acute otitis media that produces air cell opacification and coalescence on computed tomographic (CT) imaging. This appearance, however, is nonspecific and may be seen in patients with infection and tumor. Magnetic resonance imaging (MRI) can aid in differentiating the two on the basis of differences in tissue signal characteristics and by showing the presence or absence of an associated soft-tissue mass. In this report, we demonstrate the utility of MRI as a complementary imaging modality to CT in the diagnosis of a solitary plasmacytoma of the temporal bone that was initially thought to be coalescent mastoiditis. PMID- 7980908 TI - The fate of medialized cartilage in thyroplasty type I. AB - Thyroplasty type I is rapidly emerging as the preferred means of medializing a paralyzed vocal fold. We discuss our experience with the fate of a medialized cartilage window 9 months after an otherwise successful operation. Cartilage resorption over time resulted in degeneration of voice and in progressive aspiration. We recommend removing the cartilage window rather than medializing it, in the interest of stabilizing the degree of long-term vocal fold medialization. PMID- 7980910 TI - Effects of primer choice and source of Taq DNA polymerase on the banding patterns of differential display RT-PCR. PMID- 7980909 TI - Intralabyrinthine schwannoma. AB - Intralabyrinthine schwannoma is a rare tumor. Until the present time, the diagnosis, for the most part, has been made either incidentally during labyrinthectomy or described as a pathologic finding during temporal bone histologic studies. This article presents a patient with long-standing dysequilibrium and hearing loss due to an intralabyrinthine schwannoma. Diagnosis was made on the basis of a magnetic resonance imaging with gadolinium prior to surgery and confirmed pathologically on excision. PMID- 7980911 TI - Co-amplification of two cDNAs in RT-PCR can alter the yield of both products. PMID- 7980912 TI - Improvement of GC-rich template amplification by inverse PCR. PMID- 7980913 TI - A simple method using T4 DNA polymerase to clone polymerase chain reaction products. PMID- 7980915 TI - An acetylated (nuclease-free) bovine serum albumin in a PCR buffer inhibits amplification. PMID- 7980914 TI - A PCR artifact under low-stringency conditions due to amplification by only one primer. PMID- 7980916 TI - Direct sequencing of double-stranded PCR products gel purified by centrifugation through blotting paper. PMID- 7980917 TI - Screening transgenic mice by PCR: detection of tandem repeats. PMID- 7980918 TI - A plasmid vector, pTG-link, for convenient assembly of DNA fragments for transgenic animal production. PMID- 7980919 TI - Recombinant proteins attached to a nickel-NTA column: use in affinity purification of antibodies. PMID- 7980920 TI - Odorless SDS-PAGE of proteins using sodium 2-mercaptoethanesulfonate. PMID- 7980921 TI - Quantitative determination of phosphorothioate-modified oligodeoxyribonucleotide persistence. PMID- 7980922 TI - A simple method for reusing western blots on PVDF membranes. PMID- 7980923 TI - Analysis of the endA mutation of Escherichia coli K12 strains: JM103 behaves like endA+ wild-type strains. PMID- 7980925 TI - Use of agarose block DNA to make cosmid libraries. PMID- 7980924 TI - Removal of polysaccharides from plant DNA by ethanol precipitation. PMID- 7980926 TI - Detergent affects silver sequencing. PMID- 7980927 TI - Isolation of P1 insert ends by direct sequencing. PMID- 7980928 TI - Klenow co-sequencing: a method for eliminating "stops". PMID- 7980929 TI - Boiling eliminates artifact banding when sequencing double-stranded templates. PMID- 7980930 TI - High throughput PCR procedure for up to 6-kb lengths of DNA. PMID- 7980931 TI - Simple method to reduce background on autoradiographs. PMID- 7980932 TI - Variations on cycle sequencing. AB - Linear amplification or cycle sequencing is an advance that has made the use of automated fluorescent DNA sequencing instruments truly practical for large-scale genome analysis. We have investigated several variations of our standard cycle sequencing method. First, we have reduced the number of amplification cycles, which resulted in improved data quality and faster sequencing. Second, we have used different thermostable enzymes, which again improved data quality. Lastly, we have devised a method for precipitating reaction products in 96-tube trays. Together, these variations have allowed us to develop an improved cycle sequencing method that significantly increases sequencing throughput, improves efficiency and data quality, and reduces the cost of sequencing reactions. PMID- 7980933 TI - Improved fluorescent cycle sequencing protocol allows reading nearly 1000 bases. AB - Recently available thermostable DNA polymerases result in enhanced resolution and accuracy compared to thermal enzymes used previously in fluorescent cycle sequencing. These new enzymes produce less variations in peak intensities, enhance gel resolution and are less sensitive to unspecific termination caused by either DNA structure or impurities in the DNA preparation. Optimization of nucleotide ratios and the usage of high concentrations of detergents in the sequencing reaction result in sequence readings up to 1000 bases and improve overall reliability of the sequencing protocol; this works successfully in about 90% of cases. PMID- 7980934 TI - Simultaneous mutagenesis of antibody CDR regions by overlap extension and PCR. AB - A method for the facile simultaneous mutagenesis of complementary-determining regions (CDRs) in a single chain antibody (scFv) is described. Overlapping sets of oligonucleotides containing random sequences within the CDRs corresponding to the heavy chain variable region (VH) jointed to a linker peptide (J) and the light chain variable region (VL) were extended under PCR conditions to full length genes. These gene products were then further amplified using short PCR primers containing complementary overlaps between the 3' and 5' ends of the VH-J and VL genes respectively. In a final step, the VH-J and VL gene products were mixed and assembled into scFv DNA products by overlap extension under standard PCR conditions. Sequence analyses indicated that the method is basically successful. However, some deletions were observed, which probably reflects difficulties in the automatic synthesis of long degenerate oligonucleotides. PMID- 7980935 TI - A nontoxic and versatile protein salting-out method for isolation of DNA. AB - A pivotal technique in basic and applied molecular biology is the isolation of DNA. However, the present DNA extraction methods are either toxic, expensive, time-consuming and laborious or restricted to certain applications. Here we describe a nontoxic and versatile protein salting-out method for convenient and rapid extraction of large as well as small DNA molecules from vertebrate cells and plasmid DNA from bacteria. Easy and relatively imprecise manipulations of a large number of samples result in high yields of pure mammalian and plasmid DNA that are suitable for transformation of bacteria, restriction enzyme analyses, Southern blotting, end labeling of DNA, PCR and sequencing. PMID- 7980936 TI - Polyvinyl alcohol enhances detection of low abundance transcripts in early stage quail embryos in a nonradioactive whole mount in situ hybridization technique. AB - We have tested the ability of polyvinyl alcohol (PVA) to enhance the indoxyl nitro blue tetrazolium alkaline phosphatase color reaction in whole mount in situ hybridizations of early stage quail embryos. Using detection of the myogenic factor qmyoD in hybridizations of 13-14 somite-pair quail embryos as a test system, 10% solutions of 13-23 kDa and 31-50 kDa PVA optimally enhanced the alkaline phosphatase color reaction. With the enhanced detection conditions, we have been able to measure qmyoD expression as early as the 3 somite-pair stage, whereas previously we were unable to detect qmyoD prior to the 10 somite-pair stage. PVA-enhanced detection of somitic qmyoD expression was specific as no corresponding signal was found in control hybridizations with a sense qmyoD probe. PMID- 7980937 TI - Processing of cDNA and genomic kilobase-size clones for massive screening, mapping and sequencing by hybridization. AB - Efficient procedures for managing a large number of M13 or plasmid clones have been developed. In addition to picking, clones are directly arrayed in multiwell plates by dispensing diluted transformation mixtures. Metal pin arrays are used for fast inoculations of preparative plates filled by medium or by PCR mixture. Growth of M13 clones in multiwell plates is optimized to obtain a consistently high yield, and a PCR protocol is defined for reliable amplification of several thousand M13 or plasmid inserts per day in BioOvens. Over 80,000 cDNA inserts have been amplified. The phages or amplified inserts are spotted on nylon filters using an array of pins having a flat bottom, 0.3 mm in diameter. The procedures are suitable for an automated processing of hundreds of thousands of short clones from representative cDNA and genomic libraries. Hybridization of arrayed clones with oligonucleotide and complex probes can simplify the search for new genes and accelerate large-scale sequencing. PMID- 7980938 TI - HRRI: a high resolution radioimager for fast, direct quantification in in situ hybridization experiments. AB - We present a high-speed, high-resolution beta imager. It has been developed to be used in in situ hybridization experiments, either instead of or in complement with autoradiographic film and emulsions that are currently used for these experiments. It allows the user to locate and perform quantitative analyses of (3H-, 14C-, 35S-, 32P-, 125I-) labeled molecules with a 15-microns spatial resolution on a 1.2 cm2 area. We have combined recent techniques (specific scintillator thin sheets and intensified charge-coupled device [CCD]) so that this imager offers a wide dynamic range and real-time acquisition. Several biological applications will be discussed. PMID- 7980939 TI - A rapid FISH technique for quantitative microscopy. AB - Results of quantitative microscopy for fluorescence in situ hybridization (FISH) signals with repetitive DNA probes (pUC 1.77 and D15Z1) are reported. A nonenzymatic hybridization technique was applied using fluorescein-12-dUTP labeled DNA probes and a buffer system not containing any formamide or equivalent chemical denaturing agents. Following thermal denaturation, the renaturation time was reduced to less than 30 min. The number of wash steps was reduced to one. For the pUC 1.77 probe, the major binding sites (chromosome 1) were distinguished from the minor binding sites by means of fluorescence intensity and spot size. The intensity variation of the two brightest FISH spots (major binding sites) in the same metaphase was 19% for 15 min renaturation time and 16% for 30 min renaturation time. For the D15Z1 probe, generally four bright spots were visible and tentatively assigned according to chromosome length and centromere position (chromosomes 15 and 9). The intensity variation of each two homologues in the same metaphase spread showed a coefficient of variation of 47% (15 min) and 22% (30 min) for chromosome 15, and 19% (15 min) and 15% (30 min) for chromosome 9. The results indicate that the applied technique can considerably accelerate the FISH procedure and is suited for quantitative microscopy. PMID- 7980940 TI - Adenovirus-mediated transfection of cultured cells. AB - We describe here a simple and efficient transfection method for transient expression of cloned genes in cell lines and primary cultured cells. The method involves the use of DEAE-dextran to target DNA to the cellular endocytotic pathway and the use of a human adenovirus to ensure efficient lysis of endosomal vesicles. The procedure allows effective delivery of DNA into the cytoplasm and, therefore, results in a higher fraction of cells expressing exogenous proteins. Using this method, we routinely obtain 60%-90% of COS cells or Chinese hamster ovary cells expressing beta-galactosidase, as determined by in situ staining with 5-bromo-4-chloro-3-indolyl-beta-D-galactoside (X-gal). We have also obtained much improved levels of expression in cells that are difficult or impossible to use in transient expression assays, such as rat-1 fibroblasts or primary osteoblast cultures. We successfully used the method to express heteromeric proteins that require subunit assembly for proper function. The method also proved effective to express functions in which the exogenous protein needs to couple to the endogenous cellular machinery. Thus, this transient transfection method should prove valuable for many functional studies in a broad variety of cell lines and primary cultures. PMID- 7980941 TI - Effect of different antibiotics on efficiency of transformation of bacteria by electroporation. AB - We noted large differences in the transformation efficiency of Escherichia coli when different methods were used for transformation. To analyze these observations, the ampicillin and tetracycline resistance plasmid, pBR322, was transformed into HB101 and DH5 alpha E. coli using calcium chloride or electroporation, and the clones containing the plasmids were selected under various conditions. Electroporation yielded around 5 x 10(7) transformants per microgram of plasmid DNA when ampicillin was used for selection, but only 5 x 10(5) transformants per microgram when tetracycline was used. A calcium-chloride method of transformation showed no differences between the two antibiotics. The loss of efficiency of electroporation in the presence of tetracycline was also seen with three tetracycline-related antibiotics and could be blocked by chelating agents. It was also overcome by a 3-h preincubation of the bacteria before exposure to antibiotic. D-Cycloserine showed a selective effect on electroporated bacteria, but Polymyxin-B, chloramphenicol or phosphonomycin did not. The mechanism of inhibition by tetracycline-related antibiotics is not known, but the results show that the recovery of electroporated bacteria may be significantly decreased if these antibiotics are used. PMID- 7980942 TI - Analysis of lentiviral genomic variation by denaturing gradient gel electrophoresis. AB - Retroviruses are known for their genetic variability. In any infection, several genotypes usually exist within the host. We have used denaturing gradient gel electrophoresis to study genetic variation of ovine lentiviruses. Starting with viral DNA from cells infected in vitro, a portion of the envelope gene was amplified by PCR, and the products were analyzed by DGGE. With this technique we have been able to detect sequence variations between and within virus isolates and to show evolution of the predominant viral species upon in vivo passage. PMID- 7980943 TI - Pregnancy-associated endometrial expression of antileukoproteinase gene is correlated with epitheliochorial placentation. AB - Uterine expression of the mRNA encoding antileukoproteinase (ALP) is highest in pig uterus during mid- to late pregnancy, suggesting a stage of pregnancy dependent role for this elastase/cathepsin G protease inhibitor in feto-maternal interactions. To examine a potential relationship between uterine synthesis of ALP and the type of placentation in mammalian species, the expression of ALP mRNA and/or protein in pregnant mares, cows, rats, and mice was evaluated. Genomic DNA and mRNA hybridization analyses were performed using a porcine ALP cDNA as probe. The concentration of ALP protein in reproductive tissues was determined by RIA using a polyclonal antibody raised against a synthetic peptide (ALP 16P) corresponding to amino acid residues 21-36 of the porcine ALP protein. A single ALP mRNA transcript of approximately 0.8 kb in length was detected in equine and bovine uterine tissues. The relative abundance of ALP mRNA in equine endometrium increased between days 125-170 (mid-pregnancy), and then decreased by day 215 of pregnancy. Similarly, the steady state levels of ALP mRNA in bovine endometrium and myometrium were higher during mid- to late than during early pregnancy. The levels of ALP mRNA in bovine fetal cotyledon were low and did not change significantly with stage of pregnancy. No hybridization was detected to pregnant rat endometrial tissues, although high stringency Southern blot analysis of porcine, bovine, and rat genomic DNAs using porcine ALP cDNA as probe predicted a high degree of nucleotide sequence homology in their respective ALP genes.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7980944 TI - Characterization and properties of steroid binding protein in Bufo arenarum serum. AB - Serum steroid binding properties of mature Bufo arenarum females were studied. Binding data obtained using charcoal adsorption assay and equilibrium dialysis methods indicates a single protein, named Bufo arenarum sex binding protein (Ba SBP), which binds 5 alpha-dihydrotestosterone (DHT), testosterone (T), and estradiol-17 beta (E2) with high affinity (10(-7) M-1 - 10(8) M-1) and fair capacity (10(-6) M). Scatchard plot analysis demonstrated the coexistence of two binding sites. Ba SBP has a sedimentation coefficient of 5.2 S in sucrose gradient centrifugation in low salt and under steady-state conditions. The specificity of this protein, determined by competitive binding experiments, is comparable to human SBP. DHT and T bind with higher affinity than E2. Estriol and estrone competed poorly, while diethylstilbestrol and C21 steroids did not compete. The binding capacity of this protein is under estrogenic control. PMID- 7980945 TI - Effect of IGF-I on pig oocyte maturation, fertilization, and early embryonic development in vitro, and on granulosa and cumulus cell biosynthetic activity. AB - Porcine granulosa cells have been shown previously to both secrete and respond to insulin-like growth factor-I (IGF-I), suggesting an autocrine function of this peptide in the follicle. The present work was undertaken to determine possible effects of IGF-I on in vitro maturation, in vitro fertilization, and early embryonic development in culture. Granulosa and cumulus cell proliferation and differentiation based on 3H-thymidine uptake and progesterone production, respectively, were also assessed. The results showed that the cleavage rate of oocytes was markedly stimulated in a dose-dependent manner by the addition of IGF I to the oocyte maturation medium (P < 0.05). Embryo development beyond the 8 cell stage was improved by IGF-I, reaching a maximum of 22% at 200 ng/ml IGF-I. Treatment with IGF-I after fertilization increased the percentage of total oocyte cleavage (P < 0.05) to approximately 52%, 43%, and 57% at, respectively, 25, 50, and 100 ng/ml IGF-I. 3H-thymidine incorporation by granulosa cells was significantly increased in cultures treated with FSH (3-fold) or IGF-I (6-fold) compared to the control. For the cumulus cells, FSH caused a similar increase (3 fold) in 3H-thymidine incorporation while IGF-I stimulated a 15-fold increase. Progesterone production by the granulosa cells was increased to the same extent by treatment with FSH or IGF-I (4.7 and 5.1-fold, respectively). However, for the cumulus cells, while FSH caused a marked 16-fold increase in progesterone production, IGF-I caused only a marginal increase of 2.5-fold.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7980946 TI - Parthenogenetic development of bovine oocytes matured in vitro for 24 hr and activated by ethanol and cycloheximide. AB - This research was undertaken to improve development of parthenogenetic embryos following various combined treatments of ethanol and cycloheximide. In Experiment 1 in vitro matured oocytes (IVM, 24 hr) were treated with 7% ethanol for 5 min followed by incubation in 10 micrograms/ml cycloheximide in Medium 199 for 0 (control), 5, 10, and 20 hr. Development to 2-8 cells following culture for 3 days was similar among treated groups (32-41%; P > 0.05), which was higher than that of controls (6%; P < 0.05). Experiment 2 compared pre-ethanol exposures for 0, 1, 2.5, and 5 min, followed by 5 hr cycloheximide treatment on activation development. One- to 5-min groups resulted in 42-44% cleavage contrasted to 1-12% for controls (P < 0.05). Experiment 3 examined the effect on oocyte development of ethanol and different concentrations of cycloheximide (0, 1, 5, and 10 micrograms/ml). Cleavage to 2-8 cells was similar among the 5 and 10 micrograms/ml cycloheximide groups (36% and 42%, P > 0.05) but lower (P < 0.05) for the 1 micrograms/ml group (24%) and the controls (2-13%). When 5 micrograms/ml cycloheximide was used (Experiment 4), pre-exposure to ethanol (1, 2.5, and 5 min) resulted in more oocytes cleaved (38-41%) than in the cycloheximide alone group (0%) or the control (0%, P < 0.05). Experiment 5 tested blastocyst development of the activated oocytes with or without cytochalasin B treatment.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7980947 TI - Biochemical characterization of the boar sperm 42 kilodalton protein tyrosine kinase: its potential for tyrosine as well as serine phosphorylation towards microtubule-associated protein 2 and histone H 2B. AB - The majority of cellular responses to changing environmental conditions is regulated by protein kinases. Spermatozoa have many special properties, including motility with demonstrated chemotaxis, the ability to undergo capacitation, and the acrosome reaction, which are in part controlled by extracellular signals and in which sperm kinases are considered to be involved. We have previously reported that there is a protein kinase activity, which phosphorylates the synthetic substrate poly-(Glu, Tyr) with a Km value of 2.3 microM, and is inhibited by the tyrosine kinase inhibitor tyrphostin, in the protein extract from boar spermatozoa (Berruti and Porzio, 1992: Biochim Biophys Acta 1118:149-154). Now we have demonstrated that the enzyme is cytosolic, is active as a monomer of M(r) 42,000, is stimulated by Mg2+ > Mn2+ but not by Ca2+, is renaturable, and can phosphorylate native protein substrates such as microtubule-associated protein 2 (MAP2) and histone H2B both on the tyrosine and serine residues. N-terminal sequence analysis suggests that it is a novel protein. These new findings imply that the boar sperm 42 kD kinase may be a novel member of the emerging class of dual-specificity protein kinases, and they raise the intriguing question of its function in the protein kinase network mediating signal transduction in mammalian spermatozoa. PMID- 7980948 TI - Antibody-induced changes on rabbit sperm surface inhibit gamete interaction. AB - Interaction of specific ligands with cell surface molecules may induce reorganization of surface components. A monoclonal antibody (B-12) against sperm surface antigens of 40kDa size induced molecules on the plasma membrane overlying the acrosome of rabbit sperm to cluster in small aggregates at 0 degree C (patching). At an elevated temperature of 37 degrees C these clusters of antigen antibody complexes collected into a large aggregate on one pole of the cell forming a cap (capping). This cap-like structure showed a reduction in size over a period of time and eventually disappeared from the sperm surface. Inhibition of capping by sodium azide indicated that it is an energy-dependent process. Patching of antigens did not require energy. Involvement of sperm head cytoskeleton in the process of capping was evident from potentiation of cap formation by cytoskeleton disrupting agents like cytochalasin B and D. Patching of antigen antibody complexes was not affected by either of the agents. The loss of antigen antibody complexes from sperm surface was mainly due to shedding of the complexes in the surrounding media. Sperm with patches of antigen antibody complexes did not adhere to oocytes. Sperm from the group where a majority of the sperm were denuded of the antigen antibody complexes also did not bind to oocytes. PMID- 7980949 TI - Purification and characterization of beta-glucuronidase from bull seminal plasma and its role in fertilization. AB - Bull seminal plasma contains high levels of beta-glucuronidase. The present study describes the isolation and characterization of beta-glucuronidase, and its role in fertilization. beta-glucuronidase was purified by ion exchange chromatography, saccharolactone-agarose affinity chromatography, and gel filtration. The specific activity of the purified enzyme was 4,414 mumoles/mg protein/min. The purified enzyme showed a single band on 7.5% PAGE. On SDS-PAGE, the enzyme appeared to consist of four identical subunits of M(r) 75,000 each. The apparent Km and Vmax for beta-glucuronidase were 0.4 mM and 5.7 mumol/min using phenolpthalein mono beta-glucuronic acid as the substrate. beta-glucuronidase appeared to accelerate the cumulus dispersion in vitro. PMID- 7980950 TI - Modulation of spermatozoa and zona pellucida properties by the soluble acrosome reaction-inducing factor of the ovulated egg-cumulus complex. AB - Three sources of hamster periovulatory fluids (+/- heat inactivation at 56 degrees C), with bovine serum albumin (BSA) as control, were tested for effects on penetration of three classes of eggs by hamster sperm precapacitated in BSA. These fluids were a soluble extract of cumulus oophorus fluid (COF) from the ovulated hamster egg-cumulus complex, serum, and follicular fluid. Egg types were ovulated, salt-stored (ovulated), and follicular. In both COF and serum, there were significant differences among egg types in mean penetration, and significant effects of fluid addition. In contrast, there was no effect of follicular fluid and no differences between follicular and stored eggs. For the follicular eggs (combined data, normalized, ranked), patterns of response to the three factors (+/- heating) were different: only unheated COF and heated serum increased penetration significantly above BSA control levels (average rank 20.2, 41.4, 38, for BSA, COF (unheated), serum (heated), respectively). This indicated that the active component in COF was heat labile, not present in either serum or follicular fluid, and, therefore, of oviductal origin. Oviduct and/or COF exposure of eggs and sperm was tested for effects as an acrosome reaction inducing factor (ARIF) for acrosome reactions (AR; zona-bound and free-swimming sperm) and on sperm:zona binding and penetration. The COF ARIF for free-swimming sperm AR was heat stable. Penetration of follicular eggs increased after incubation in COF prior to sperm addition, but a greater response occurred when COF was added to eggs with sperm. In kinetic experiments, 25 min following sperm attachment, follicular eggs had lost 41% of initially bound sperm, vs. 23% for ovulated eggs, and had only 16 AR sperm/egg, vs. 26 for ovulated. Follicular eggs incubated in COF (then washed three times) had the same number of bound AR sperm as ovulated eggs. Acid solubilized zona pellucida (ASZP) from ovulated eggs was more effective as an ARIF per zona than ASZP from follicular eggs. Zonae of follicular eggs, as evidenced by dissolution times in beta-mercaptoethanol (beta MEOH), were not "harder" than those of ovulated eggs. There were differences in lectin binding antigens on zonae of both fresh and stored, follicular and ovulated, eggs. We conclude that multiple biological factors orchestrate sperm:egg interactions in the ampulla. Our data are consistent with the presence of at least three effective components: 1) the oviductal lectin-binding antigen (ZPO or oviductin), 2) an additional heat-labile component, and 3) the heat stable ARIF for free-swimming sperm. PMID- 7980951 TI - Surface alterations of the bovine oocyte and its investments during and after maturation and fertilization in vitro. AB - Surface characteristics of the bovine oocyte and its investments before, during, and after maturation, and fertilization in vitro were evaluated by scanning electron microscopy (SEM). Oocyte diameters were also measured during SEM analysis of the oocyte. The cumulus cells manifested a compact structure with minimal intercellular spaces among them in the immature oocytes. These became fully expanded with increased intercellular spaces after maturation in vitro, but contracted again after fertilization. The zona pellucida (ZP) showed a fibrous, open mesh-like structure in the maturing and matured oocytes. The size and number of meshes on the ZP decreased dramatically after fertilization. The vitelline surface of immature oocytes was characterized by distribution of tongue-shaped protrusions (TSPs) varying in density. After 10 and 22 hr of maturation incubation, oocyte surface microvilli (MV) increased to become the predominant surface structure, and TSPs decreased substantially. The vitelline surface of fertilized oocytes (at 6 and 20 hr) was similar to that of the matured oocytes, but unfertilized oocytes had less dense MV than did fertilized oocytes (at 20 hr). The diameter of the oocytes decreased from 99 to 80 microns during maturation and increased to 106 microns after insemination (P < 0.05). Membrane maturation was characterized by surface changes from a TSP-predominant pattern to a MV-predominant pattern. Thus, the bovine oocyte maturation process was found to involve the expansion of cumulus cells and the maturation of the ZP, which changes dramatically upon fertilization. Also, volumetric changes occurred in ooplasm processed for SEM following oocyte maturation and insemination. PMID- 7980952 TI - Expression of scatter factor/hepatocyte growth factor is regionally correlated with the initiation of sperm motility in murine male genital tract: is scatter factor/hepatocyte growth factor involved in initiation of sperm motility? AB - Based upon findings that the scatter factor/hepatocyte growth factor (SF/HGF) has strong mitogenic and motogenic properties, and that the sperm cell acquires its fertilizing capacity and motility in the distal parts of mammalian epididymis, the present study was conducted to investigate the role of SF/HGF in initiation of sperm cell motility. This was investigated by determining the expression of SF/HGF in various regions of the murine male genital tract by scatter and cell tracking assays using MDCK epithelial cells, Western blot procedure, and the immunohistochemical procedure using paraffin sections of various regions of the male genital tract. The findings from all these assays indicate that SF/HGF is differentially expressed in various parts of the male genital tract with slight or no expression in the testes, caput epididymis, and vas deferens, and with the highest expression in cauda and corpus (distal) epididymis followed by expression in the corpus (proximal) epididymis. This region-specific SF/HGF expression pattern coincides with the pattern of acquiring the fertilizing capacity and motility by the sperm cell during its transit through the male genital tract. However, wherever SF/HGF was expressed in the male genital tract, its molecular weight was slightly higher (Mr, 82 kD), compared to the SF/HGF expressed in various other somatic tissues (Mr, 78 kD), indicating that the genital tract SF/HGF may be a different molecular species that shares some immunoreactive epitopes with the somatic cell SF/HGF. Incubation of immotile sperm from caput epididymis with the purified human placental SF/HGF of 78 kD initiated motility in 5-15% of sperm population. These results strongly suggest that the SF/HGF-like activity is expressed in the male genital tract in a region-specific manner, and this activity may have a role in initiation of sperm motility acquired during its transit through the epididymis in mammals. PMID- 7980953 TI - Characterization of chromatin-condensing proteins during spermiogenesis in a neogastropod mollusc (Murex brandaris). AB - During the process of chromatin condensation in the spermiogenesis of the neogastropod mollusc Murex brandaris, the nuclear protein complement undergoes a complex series of changes. These changes lead to the appearance of three small protamines in the ripe sperm nuclei. We have characterized this system electrophoretically and at the compositional level, as well as through the analysis of crossreactions with antibodies elicited against a specific spermatozoan protamine. Our results indicate that the complex pattern of chromatin condensation during spermiogenesis in this species (M. brandaris) may be modulated by a series of post-translational (and intranuclear) modifications of DNA-interacting proteins, such as precursors to the sperm protamines. The amino acid composition of each sperm protamine is remarkably simple (lys + arg + gly > or = 96 mol%). This system of spermiogenic/spermatozoal proteins in the neogastropod M. brandaris clearly differs from that in patellogastropods and archaeogastropods, and it may be helpful in understanding evolutionary changes in the chromatin condensation pattern during the spermiogenesis of gastropod molluscs. PMID- 7980954 TI - Attachment of the ascidian sperm surface egg receptor N-acetylglucosaminidase to the cell membrane. AB - Ascidian sperm bind to vitelline coat N-acetylglucosamine groups of the egg via sperm surface N-acetylglucosaminidase. This sperm surface egg receptor remains anchored throughout penetration. Localization to the sperm surface was verified by biotinylation of intact sperm followed by solubilization in Triton X-100 and binding to streptavidin agarose. The enzyme was determined to be an integral membrane protein as judged by resistance to release by Kl and high pH. Linkage of the enzyme to the sperm surface was probed through differential solubilization followed by measuring released enzymatic activity with a fluorogenic substrate. Nonionic detergents released 90% of the activity. Proteases released about 40%. No activity was released by a phosphatidylinositol specific phospholipase C. This finding, combined with the similarity of release level by all the detergents, including Triton X-100 and octylglucoside, argues against a phosphatidyl-inositol linkage. The release form enters the hydrophilic phase of a Triton X-114 phase separation experiment. This observation, coupled with the findings of release by nonionic detergents, suggests that the protein is hydrophilic once released from the membrane. Thus, although clearly an integral membrane protein, the enzyme has limited hydrophobicity such as would be present in a single transmembrane sequence or extensive glycosylation. PMID- 7980955 TI - Connectivity of cancellous bone: assessment and mechanical implications. PMID- 7980956 TI - Expression of bone morphogenetic protein genes in the human dental pulp cells. AB - Dental pulp has a potential to induce ectopic bone formation, but little is known about its mechanism. We thought that bone morphogenetic proteins (BMPs), members of the transforming growth factor-beta (TGF-beta) superfamily, are involved in the osteoinductive activity of dental pulp. In order to prove this assumption, we constructed a cDNA library from primary culture cells of human dental pulp (HDP cells), and screened the library with previously cloned cDNAs for mouse BMP-2 and -6 as probes. Three distinct cDNA clones encoding human BMP-2, -4 and -6 were isolated. By Northern blot analysis, specific transcripts of the genes of those BMPs were detected in the HDP cells. It was concluded that the BMPs were expressed in a certain population of dental pulp cells and might play some roles in ectopic bone formation by dental pulp. PMID- 7980957 TI - Progressive osseous heteroplasia: a case report. AB - We report the case of a young female who, from infancy, suffered extensive, progressive, heterotopic ossification of her left lower limb. Heterotopic ossification, which was largely but not exclusively intramembranous in type, was most marked in subcutaneous fat but was also noted in muscle and deep connective tissue. The spectrum of changes noted suggests that this congenital disorder of soft tissues is similar to that recently described as progressive osseous heteroplasia. PMID- 7980958 TI - Microradiographic aspect on iliac bone tissue in postmenopausal women with and without vertebral crush fractures. AB - Bone mass, microstructure and microconnectivity of cancellous bone tissue, microporosity, and microdensity of cortical bone have been evaluated with an image analysing computer on microradiographs in 34 iliac crest bone biopsies from two individual, paired age-matched groups of postmenopausal women. Group 1 comprised 17 cases without vertebral crush fractures (mean age 66 years, range 45 80 years) and time since menopause 20.5 +/- 11.5 years. The second group were 17 cases with vertebral crush fractures (mean age 67 years, range 48-86 years) and time since menopause 16.5 +/- 7.6 years. No differences were observed either in bone mass or in Parfitt's indices of the microarchitecture of their cancellous bone tissue. However, both groups 1 and 2 were different by the number of the structure elements per 30 mm2 of tissue volume and the trabecular bone pattern factor (TBPF) being higher in group 1 than in group 2 (p < 0.005)--showing a better connectivity of bone network in group 2 with crush vertebral fractures than in group 1. The number of terminus to terminus struts of the trabecular bone pattern is increased in group 1 (p < 0.001). On 7-microns stained sections the active cancellous eroded perimeter (Cn.Oc.Pm/B.Pm) is greater in group 1 than in group 2 (p < 0.02). Therefore, in these two populations with a similar degree of osteopenia, a decrease of trabecular connectivity does not provide an explanation of bone fragility and the occurrence of vertebral crushed fractures. PMID- 7980959 TI - Effects of prostaglandin E2 and risedronate administration on cancellous bone in older female rats. AB - The effects of Prostaglandin E2 (PGE2) and Risedronate (Ris) both separately and in combination (PGE2 + Ris) were studied on the intact aged female rat skeleton to determine whether the combination of PGE2 with an antiresorptive agent is more effective anabolically than PGE2 alone. Nine-month-old Sprague-Dawley rats were injected subcutaneously either with vehicle, 6 mg PGE2/kg per day, 1 or 5 micrograms Ris/kg twice a week, or 6 mg PGE2/kg per day plus 1 or 5 micrograms Ris/kg twice a week (PGE2 + 1 Ris or PGE2 + 5 Ris) for 60 days. After the treatment, we determined the longitudinal bone growth rate, the qualitative appearance of the primary spongiosa (PS), and the static and dynamic bone histomorphometry of the secondary spongiosa (SS) of the proximal tibial metaphysis (PTM) by examining undecalcified longitudinal sections after double fluorescent labeling. The relative effects of these treatments on longitudinal bone growth were ranked as follows: PGE2 + 5 Ris > PGE2 + 1 Ris = basal > PGE2 > 1 microgram Ris = 5 micrograms Ris = aging. The density of the PS was ranked as follows: PGE2 + 5 Ris > PGE2 + 1 Ris = PGE2 = 5 micrograms Ris = 1 microgram Ris > basal = aging. The increase in density of the PS was the result of stimulated longitudinal growth and the action of bisphosphonate. Bone mass in the SS was ranked as follows: PGE2 + 5 Ris = PGE2 + 1 Ris = PGE2 > 5 micrograms Ris = 1 microgram Ris = aging = basal.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7980960 TI - In the ovariectomized rat, tamoxifen conserves bone similarly in parathyroid intact and parathyroidectomized animals. AB - To examine the ability of tamoxifen (TAM) to conserve bone in the estrogen deficient ovariectomized (OVX) rat in the presence and absence of parathyroid hormone (PTH) six groups of rats with 45Ca-labeled bones were studied for 12 weeks. Rats were OVX, parathyroidectomized (PTX), or given sham operations and treated with TAM (10 mg/kg body wt./wk subcutaneously) or TAM-vehicle. Treatments were: group 1 = Sham-OVX; group 2 = Sham-OVX + TAM; group 3 = OVX; group 4 = OVX + TAM; group 5 = OVX + PTX; and group 6 = OVX + PTX + TAM. To monitor bone resorption serial measurements of urinary hydroxyproline and 45Ca excretion were made during the study. Ovariectomy raised these markers of bone breakdown and caused significant osteopenia, whereas TAM prevented ovariectomy increasing urinary hydroxyproline or 45Ca and conserved bone. Final total body calcium values (TBCa) in groups 1-6, respectively, were (mg +/- SD): 3240 +/- 300; 3260 +/- 289; 2750 +/- 231; 3212 +/- 312; 2742 +/- 199; and 3387 +/- 252. Thus ovariectomy reduced TBCa similarly in the presence and absence of the parathyroids (p < 0.001). In contrast TAM fully protected both PT-intact and PTX rats from the osteopenic effect of ovariectomy, despite the fact that PTX rats had a lower rate of bone turnover than PT-intact rats. However, TAM-treated OVX rats had shorter femora than OVX rats given TAM-vehicle, suggesting that TAM suppresses growth of the long bones to some degree in estrogen-deficient animals.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7980961 TI - The distribution of soluble, mineral-bound, and matrix-bound proteins in osteoporotic and normal bones. AB - Very little is known about the composition of noncollagenous protein (NCP) in osteoporotic bone. We have obtained osteoporotic (OP) cancellous bone samples from 2-4 cm below the surface of human femoral heads and compared the protein profiles to age-matched (old controls, OC), as well as young autopsy controls (YC). The proteins were analyzed using a serial extraction method which liberates proteins from distinct pools; first, proteins were extracted in 4.0 M GuHCl (G1), followed by the extraction of mineral-bound protein with 0.5 M EDTA (E), and finally the protein previously masked by the mineral was released by a second 4.0 M GuHCl extraction (G2). The tissue residue was digested with bacterial collagenase liberating proteins bound to the collagenous matrix. Uniform bone preparations of finely ground bone powder were used for our study. The protein content of the four groups was determined together with the protein distribution using amino acid analysis and gel-electrophoresis. Our data indicate that the noncollagenous protein content is considerably reduced in osteoporotic bone when compared with age-matched or young controls, whereas the collagen content is unaffected. When bone proteins were investigated using gel-electrophoresis we found a similar distribution of proteins in the G1 and E fractions of all three groups, but the osteoporotic bone samples, using densitometric analysis of the gels, showed quantitative differences in a number of the proteins. The greatest differences were observed in the G2 extract, where the NCP of osteoporotic bone was limited to a few low-molecular-weight bands when compared with the OCs or YCs.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7980962 TI - Interdependence of skeletal sclerosis and elevated circulating levels of 1,25 dihydroxyvitamin D in osteopetrotic (op and tl) rats. AB - Osteopetrosis describes a heterogeneous group of inherited, metabolic bone disorders characterized by reduced bone resorption which coexists with elevated circulating levels of 1,25-dihydroxyvitamin D [1,25(OH)2D]. To determine whether or not skeletal sclerosis and high concentrations of 1,25(OH)2D are interdependent, this study used two distinct, nonallelic osteopetrotic mutations in the rat, osteopetrosis (op) and toothless (tl). The op rat is a mutation in which skeletal sclerosis can be cured (mutant) or induced (normal) following the transfer of normal or mutant osteoclast progenitors, respectively. Although these procedures are ineffective in rats of tl stock, infusions of pharmacological doses of macrophage colony-stimulating factor (CSF-1) can stimulate bone resorption and eliminate most of the excess skeletal matrix in tl mutants. This study examined the effects of cure/induction in neonatal mutant/normal rats of op stock and CSF-1 infusions in mutant rats of tl stock on skeletal (bone resorption) and serum [1,25(OH)2D] parameters as a function of time after treatment. Osteopetrotic mutants transplanted (cured) with normal spleen cells demonstrated cellular changes in osteoclast phenotype within 2-3 days followed by histologic and radiographic evidence for increased bone resorption that culminated in a normal appearance of the skeleton by 4 weeks. The markedly elevated serum levels of 1,25(OH)2D observed in untreated mutants fell significantly in transplanted mutants by the end of the first week and were similar to those in normal littermates at 3 and 4 weeks. Normal littermates transplanted (induced) with mutant spleen cells showed a progressive increase in skeletal sclerosis paralleled by significant increases in circulating levels of 1,25(OH)2D.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7980963 TI - The mechanical strength of bone in different rat models of experimental osteoporosis. AB - In order to discover good parameters for experimental osteoporosis, we measured the failure load of the femoral neck and the bending strength of the tibia in orchidectomized (ORC) (20 rats for 4 weeks), ovariectomized (OVX) (28 rats for 6 weeks), and immobilized (IMM) (33 rats for 3 weeks) rats. Each of these operations led to a significant decrease in trabecular bone volume when compared with corresponding controls (p < 0.001). The ash weight of femurs was significantly decreased in ORC (p < 0.05) and IMM (p < 0.001) rats, but not in OVX rats. Growth of the femur was somewhat slower in ORC (p < 0.05) and IMM rats (p < 0.05), but not in OVX animals. All three osteoporosis models showed significant decreases in the maximal load of the femoral neck (ORC: 23.9%, p < 0.001; OVX: 15.8%, p < 0.001; IMM: 27.7%, p < 0.001), as well as in energy absorption (ORC: 43.9%, p < 0.001; OVX: 28.3%, p < 0.001; IMM: 45.3%, p < 0.001). In tibia orchidectomy reduced maximal strength and energy absorption significantly (10%, p < 0.01; 27.8%, p < 0.01), but ovariectomy decreased only maximal load (8.7%, p < 0.01) and immobilization only energy absorption (18.0%, p < 0.01). Our results suggest that the mechanical strength of the femoral neck is a sensitive indicator of bone loss in all three osteoporosis models. PMID- 7980964 TI - Cytokine suppressive anti-inflammatory compounds inhibit bone resorption in vitro. AB - Data from several laboratories suggest a role for a variety of cytokines in the process of bone resorption. SK&F 86002 [5-(4-pyridyl)-6(4-fluorophenyl)-2,3 dihydroimidazo(2,1-b) thiazole], a potent cytokine-suppressive anti-inflammatory agent, has been shown to inhibit cyclooxygenase (CO) and 5-lipoxygenase (LO) activity and to inhibit the production of cytokines both in vitro and in vivo. In the present study, SK&F 86002 inhibited fetal rat long bone (FRLB) resorption induced by parathyroid hormone (PTH), 1,25-dihydroxy-vitamin D3, tumor necrosis factor alpha, and Escherichia coli lipopolysaccharide in a dose-dependent (IC50 of 0.5-1 microM) and reversible manner. Under identical conditions, selective CO inhibitors (indomethacin, ibuprofen, naproxen) and 5-LO inhibitors (phenidone, SK&F 107649) were inactive. Analogs of SK&F 86002, which are dual CO/LO inhibitors devoid of cytokine inhibitory activity (SK&F 81114 and SK&F 86055), also failed to significantly inhibit PTH-induced FRLB resorption. Analogs of SK&F 86002, which retain cytokine inhibitory activity (SK&F 104493 and SK&F 105561), inhibit bone resorption. These data indicate that the observed inhibition of bone resorption by compounds of this class correlates with their cytokine suppressive activity. PMID- 7980965 TI - Age- and sex-dependent cancellous bone changes in a 4000y BP population. AB - We studied cancellous bone loss in a 4000y BP population, using several methods designed to detect age-related changes, in order to investigate the pattern of cancellous bone loss in this ancient population and to compare the results deriving from different methods used on identical specimens. We used 10-mm sections of fourth lumbar vertebral bodies and left femoral necks of 18 individuals of both sexes with estimated ages from 20 to 60 years of a 4000y BP bronze-age population. Stereoscopic photographs were used for three-dimensional analysis and trabecular number (TN) counting. After embedding, the following parameters were measured in different image analysis systems using plane parallel block samples: bone mineral density (BMD) in water by DEXA, and by evaluation of standardized radiographic images; fractional bone volume (BV/TV) in backscattered electron images of the trabecular surface layer and in optical images of trabeculae in a surface-stained layer; and trabecular bone pattern factor (TBPf) in the latter images. There was a high correlation between the results of morphological methods for measuring fractional bone volume. Reasonable correlations were found between the x-ray photon methods and poor correlations between these and the morphological methods. These poor correlations may be due to the diagenetic substitution occurring in archaeological skeletons, which would strongly influence x-ray-based density measurements. However, all the methods demonstrated that the most dramatic loss of quantity and quality in cancellous bone occurred in females between 40 and 60 years.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7980966 TI - Epidemiology and clinical features of osteoporosis in young individuals. AB - Due to the lack of epidemiologic data on osteoporosis in the young, we identified all 22 Olmsted County, MN, residents aged 20-44 years when first diagnosed with established osteoporosis in 1976-1990. The overall age- and sex-adjusted incidence rate was 4.1 per 100,000 person-years (95% CI 2.4-5.9) with a female to male ratio of age-adjusted rates of 1.2:1. The majority represented secondary osteoporosis (12 steroid-induced, 3 postmenopausal, 2 delayed puberty, 2 anticonvulsant-induced, 2 gastrointestinal disease, 2 alcoholism, 1 anorexia nervosa, and 7 other etiologies; some individuals had more than one factor present) but two had idiopathic osteoporosis (incidence 0.4 per 100,000 person years, 95% CI 0-0.9). To further characterize the patients with idiopathic osteoporosis, we also reviewed the entire Mayo Clinic experience with such patients from 1976 to 1990, regardless of residency. A total of 56 patients (30 female/26 male) were identified with a median age at diagnosis of 34 years. Only 8% were hypercalciuric at presentation. There was a preponderance of cancellous bone fractures (vertebral 81%, rib 37%, wrist 13%), although 13% did have hip fractures. Transiliac bone biopsies were available in 18 patients. As compared to age- and sex-matched controls, the osteoporotic subjects had a significant reduction in trabecular bone volume, cortical thickness, and mean wall thickness, the latter suggesting an abnormality in osteoblast function in these individuals.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7980967 TI - Effect of long-term ovariectomy on bone mechanical properties in young female cynomolgus monkeys. AB - Feral adult female cynomolgus monkeys were divided into two groups: normal controls and ovariectomized. Tibiae and trabecular bones from the femoral head, from each group, were tested using a materials testing machine. The bending stiffness of the tibiae was measured by nondestructive three-point bending tests and their maximum torque capacity by destructive torsion tests. The compressive strength of the trabecular bones was measured by compression tests. Ovariectomy caused significant decreases in elastic modulus of the tibiae (p < 0.008), measured by three-point bending tests, and in shear modulus (p < 0.015), failure shear stress (p < 0.01), and failure torque (p < 0.001) of the tibiae, measured by torsion tests. It caused a significant decrease in cortical bone density (p < 0.005), but no significant changes in tibial cross-sectional area and in cortical shaft external and internal diameters. The differences in elastic modulus, maximum compressive strength, and density of femoral trabecular bone samples between the two groups were not significant. PMID- 7980968 TI - Regional variation of insulin-like growth factor-I gene expression in mature rat bone and cartilage. AB - Regulation of long bone growth by growth hormone and other endocrine factors is mediated by the local synthesis of IGF-I in the growth plate. Recent evidence suggests that different regions of the growth plate exhibit variable growth rates. To investigate whether IGF-I gene expression in the growth plate differs in relation to growth, we examined the distribution of IGF-I mRNA and peptide using in situ hybridization and immunohistochemistry, respectively, in the tibiae of 18-week-old rats (n = 6). Osteoblasts were identified by osteocalcin immunoreactivity, and osteoclasts by tartrate-resistant acid phosphatase (TRAP) histochemistry. The abundance of IGF-I mRNA in growth plate chondrocytes was quantified by counting the autoradiographic signal associated with each cell. IGF I mRNA was identified in chondrocytes of both the proliferative and hypertrophic zones of the growth plate. Cells in the marginal regions of both zones contained significantly more IGF-I mRNA than those in the central region (p < 0.05). In addition, IGF-I mRNA levels were greater in the periphery of the growth plate on the medial side of the tibia (p < 0.05) in which there was more active growth than the lateral side. IGF-I immunoreactivity was present predominantly in the hypertrophic zone chondrocytes and no regional differences in its distribution were observed. IGF-I mRNA and peptide were also identified in periosteal fibroblasts, notably at sites of muscle attachment to bone, and in osteoblasts at active sites of bone remodelling in the periosteal, endocortical, and endosteal bone envelopes. In the TRAP-positive osteoclasts, IGF-I immunoreactivity, but not IGF-I mRNA, was detected. In addition, both IGF-I mRNA and peptide were identified in the hemopoietic cells of the metaphyseal bone marrow, whereas only IGF-I immunoreactivity was detectable in the diaphysis. We conclude that, in the tibiae of mature rats: (i) IGF-I gene expression in the growth plate is related to its growth and/or synthetic activity; and (ii) the presence of IGF-I in osteoblasts and osteoclasts suggests its involvement in active bone growth and remodeling. PMID- 7980969 TI - The significance of transient changes in trabecular bone remodeling activation. AB - After menopause, bone turnover is increased due to an increase in the activation of bone remodeling basic multicellular units (BMUs). The importance of changes in BMU activation to bone histomorphometry data and bone volume has not received adequate attention by many skeletal researchers. Therefore, the influence of BMU activation on the above parameters was modeled by way of computer simulation, and the results were compared to data from published post-menopausal bone loss studies. Using control theory concepts, the increase in BMU activation after menopause was modeled as a zero-, first-, or underdamped (oscillatory) second order transient BMU activation response to the step input: the decline in estrogen. A computer simulation was developed to model the influence of these three transient BMU activation responses on quantitative histological surface parameters and bone volume. The transient BMU activation responses doubled the number of active BMUs. All three types of transient BMU activation responses produced a rapid 5% decline in bone volume due to increased remodeling space. Oscillations in bone volume and histologic surface parameters over time, similar in nature to those seen in studies of ovariectomized animals, were predicted by the simulation for the oscillatory activation response examined, underdamped second order. An oscillatory BMU activation response may explain some of the transient events during menopause. The increased coherence of BMUs created by such a response may increase the likelihood of trabecular perforations. the inherent nature of an oscillatory activation response may cause its detection to be overlooked and bone remodeling data to be misinterpreted.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7980970 TI - How should we use dietary fluoride supplements? AB - Since January 1993 general dental practitioners have been able to prescribe dietary fluoride supplements in the form of drops or tablets for their child patients within the conditions of service of the General Dental Service. Many GDPs may already have taken advantage of this to the benefit of their patients. However, in recent years more evidence has become available about the impact of such fluoride supplements on the teeth. PMID- 7980971 TI - Aims and objectives. PMID- 7980972 TI - Early recognition of oral cancer: a team approach. PMID- 7980973 TI - The efficacy of management of acute dental pain. PMID- 7980974 TI - The future provision of specialist oral surgery and orthodontic services. PMID- 7980975 TI - The future provision of specialist oral surgery and orthodontic services. PMID- 7980976 TI - The future provision of a specialist oral surgery and orthodontic services. PMID- 7980977 TI - The future provision of specialist oral surgery and orthodontic services. PMID- 7980978 TI - Second molar extraction. PMID- 7980979 TI - TMD series. PMID- 7980981 TI - Presenting complaints and findings in a group of patients attending a hypodontia clinic. AB - A survey is presented of the complaints and findings in a group of 451 patients referred to a multidisciplinary clinic for the management of hypodontia. The most common complaints were missing teeth, spacing in the dental arches, and poor appearance. The majority of patients were referred by their dental practitioners, and more than half were over 12 years old when first seen. Delayed referral can have educational and social consequences. Changing attitudes to dental care and the maintenance of an intact dentition are resulting in hypodontia, particularly in its more severe forms, becoming of increasing concern to children and their parents. The management of this condition is best organised via multidisciplinary specialist clinics. PMID- 7980980 TI - The acceptability of five periapical radiographic techniques to dentists and patients. AB - Dentists are now advised to use film holders as an aid to intra-oral radiography. The aim of this investigation was to compare a range of commercially available film holders for periapical radiography with the traditional bisecting angle technique using the patient's finger as support for the film, in terms of the ease of use for the dentist and patient comfort. Twelve general dental practitioners (GDPs) were asked to perform 50 periapical examinations using their conventional (bisecting angle) technique (BA) followed by 50 using, in turn, four film holders: the Stabe (S), the Eggen (E), the Rinn (R) and the 'Superbite' devices (SB). There was no difference between BA, S and SB techniques in terms of difficulty experienced by the GDPs. However, both E and R film holders led to an increase in examinations reported as 'difficult' to perform. There was no difference in patient discomfort between the BA and SB techniques, but the use of the E and R film holders and, to a lesser degree, the S film holder was associated with increased discomfort. There was no consistent association between dentists' assessments of examinations as 'difficult to perform' and patients' opinions on discomfort. It is concluded that SB film holders provide a simple means of intraoral radiographic positioning with no increase in patient discomfort. PMID- 7980983 TI - The development and evaluation of management training for general dental practitioners. PMID- 7980982 TI - Metastatic paraspinal abscess and paraplegia secondary to dental extraction. AB - An unusual case of metastatic paraspinal abscess and paraplegia is presented. This was a consequence of simple dental extractions and subsequent bacteraemia from a neglected mouth. Neurosurgical intervention and tissue culture yielded organisms almost certainly of dental origin. No alternative primary nidus of infection could be found. The importance of oral health to general health is emphasised. PMID- 7980985 TI - [Prison--hard on health. The only nurse. Interview by Marit Fonn]. PMID- 7980984 TI - Changing faces--the American way. PMID- 7980986 TI - [Prison--hard on health. Community undertaking. Interview by Marit Fonn]. PMID- 7980987 TI - [About time for similar wages. Interview by Kjell Arne Bakke]. PMID- 7980988 TI - [Mental disease--also among nurses. Interview by Kjell Arne Bakke]. PMID- 7980989 TI - [Confused about ECC's occupational health services. Interview by Bjorn Arild Ostby]. PMID- 7980990 TI - [Nursing under a different sky: Bexhill]. PMID- 7980991 TI - [Many teachers in nursing colleges]. PMID- 7980992 TI - [One does not ask there about alcoholics?]. PMID- 7980993 TI - [New Norwegian network in substance abuse care]. PMID- 7980994 TI - [Croatia: war lasts the rest of life]. PMID- 7980995 TI - [Croatia: in the pocket of helpers]. PMID- 7980996 TI - [Prison--hard on health. In a closed world]. PMID- 7980998 TI - Authorship. PMID- 7980997 TI - [Prison--hard on health. Inmate]. PMID- 7980999 TI - Fraudulent publication. PMID- 7981000 TI - Certification gives personal and professional benefits. PMID- 7981001 TI - Successful hemodialysis with a dual lumen needle. PMID- 7981003 TI - Plasma zinc response to a breakfast meal or fasting in elderly women. AB - The aim of this study was to determine whether the postprandial decline in plasma zinc concentration is altered by aging. Eleven women, between the ages of 65 and 82 yr, participated in two separate experimental protocols: a high carbohydrate breakfast trial and a fasting trial. Plasma zinc concentrations were measured from blood samples obtained at 8:00 AM (baseline fasting) and at 30-min intervals until 1:00 PM during each trial. Following the breakfast meal, plasma zinc concentrations declined 14% from 75 +/- 1 to 65 +/- 2 micrograms/dL (p < 0.05), reaching a nadir 2.7 +/- 0.2 h after the meal. This decline was significantly (p < 0.0001) greater than the 3.6% fall observed during the fasting trial. Postprandial changes in the plasma zinc concentrations were correlated with postprandial changes in serum glucose (r = -0.43, p < 0.001), serum insulin (r = 0.17, p < 0.01), and serum phosphorus (r = 0.32, p < 0.005). These data show that plasma zinc concentrations decline following food intake in elderly women in the same manner as previously described for younger adult women. PMID- 7981002 TI - Efficiency of serum copper/zinc ratio for differential diagnosis of patients with and without lung cancer. AB - We examined serum copper (Cu), serum zinc (Zn), and the serum copper/zinc ratio (Cu/Zn) in 162 patients. All of them were seen to have an abnormal shadow in the chest X-ray films, that is, 109 patients with lung cancer (LC) and 53 patients with no lung cancer (NLC). The mean Cu and Cu/Zn in LC patients were significantly higher than those in NLC patients (p < 0.05). In LC patients, Cu and Cu/Zn were higher and Zn was lower in advanced tumors than early ones. There was a significantly clear relation between Cu or Cu/Zn and the tumor (T) stages. When the relative risk (RR) of LC was estimated, it was seen that the higher Cu and Cu/Zn became, the higher RR became. Furthermore, we showed the sensitivity of the receiver operator characteristic of the test (ROC) curve for Cu, Cu/Zn, and carcinoembryonic antigen (CEA) to diagnose LC, as explained in a paragraph of methods. The determinations of Cu, Zn, and Cu/Zn are simple and inexpensive. They also appear to have a great diagnostic value in determining the local invasion of LC and as a screening test in the high-risk patients for LC. PMID- 7981004 TI - The role of the pancreas in the regulation of zinc status. AB - A low Zn diet resulted in subacute Zn deficiency in young rats. Thirty minutes after the intubation of a trace 65-Zn we determined the total tissue Zn activity in plasma, erythrocytes, liver, pancreas, bone, muscle, and proximal jejunum. Assuming the body behaved like a closed multicompartmental system in steady state, we estimated the initial Zn exchange between plasma, and the erythrocytes or these tissues. In comparison with control animals the exchanges between plasma and erythrocytes or pancreas increased threefold during subacute Zn deficiency. In the pancreas the ratio also reversed from < 1.0 to > 1.0. This confirmed earlier observations that the specific activity (kBq 65-Zn/mol Zn) increased mostly in the pancreas. By increased net Zn uptake during subacute deficiency, the pancreas Zn content remained constant in chronic Zn deficiency. We discussed the regulation of the Zn status by the pancreas. We hypothesize that the exocrine pancreas modulates Zn absorption by an exocrine ligand that enhances absorption in the jejunum during subacute deficiency: Unsaturated with Zn it binds dietary intraluminal Zn and increases the Zn absorption. The literature provides evidence in confirmation. This hypothesis explains also conflicting data on the inherited Zn malabsorption syndrome Acrodermatitis Enteropathica. PMID- 7981005 TI - Effects of germanium and silicon on bone mineralization. AB - The chemical properties of Ge are similar to Si. This study investigated whether Ge can substitute for, or is antagonistic to, Si in bone formation. Sixty male weanling Sprague-Dawley rats were randomly assigned to treatment groups of 12 and 6 in a 2 x 4 factorially arranged experiment. The independent variables were, per gram fresh diet, Si (as sodium metasilicate) at 0 or 25 micrograms and Ge (as sodium germanate) at 0, 5, 30, or 60 micrograms. Results confirmed that Ge does not enhance Si deprivation and provided evidence that Ge apparently can replace Si in functions that influence bone composition. When Si was lacking in the diet, calcium and magnesium concentrations of the femur were decreased; this was reversed by feeding either Ge and/or Si. Similar effects were found for zinc, sodium, iron, manganese, and potassium of vertebra. There were some responses to Si deprivation that Ge could not reverse; Ge did not increase femur copper, sodium, or phosphorus or decrease molybdenum of vertebra, effects that were evoked by Si supplementation. Additionally, some findings suggested that 60 micrograms Ge/g diet could be a toxic intake for the rat. On the other hand, some responses induced by Ge indicate that this element may be acting physiologically other than as a substitute for Si. Germanium itself affected bone composition. Germanium supplementation decreased Si and molybdenum in the femur and increased DNA in tibia. Regardless of the amount of Si fed, animals fed 30 micrograms Ge/g diet had increased tibial DNA compared to animals fed 0 or 60 micrograms Ge; however, tibial DNA of animals fed 30 micrograms Ge was not statistically different from those animals fed 5 micrograms Ge. Thus, Ge may be of nutritional importance. PMID- 7981006 TI - The effect of aging on the mineral status of female mice. AB - To clarify the effect of aging on the mineral status of female mice, mineral concentrations in their tissues were determined. Five 2-mo-old, five 6-mo-old, and five 10-mo-old female B10BR mice were fed a commercial diet. Iron, zinc, copper, calcium, magnesium, sodium, and potassium concentrations in the blood, liver, kidney, heart, brain, lung, and spleen of the mice were determined using a flame atomic absorption spectrophotometer. Iron concentrations in the liver, kidney, heart, brain, and spleen increased with age. Significant differences were detected between mice 2 and 6 mo of age and between mice 2 and 10 mo of age. Zinc concentrations in the heart and lung decreased significantly with age. Zinc concentrations in the heart and lung of 10-mo-old mice were significantly lower than those of 2-mo-old mice. It is noteworthy that the copper concentration in the brain of 10-mo-old mice was markedly higher compared with that of younger mice. Calcium accumulation was apparent in the kidney of mice at 10 mo. PMID- 7981007 TI - Effect of bile/pancreatic secretions on absorption of radioactive or stable zinc. In vivo and in vitro studies. AB - Biliary/pancreatic (B/P) secretions are a major component of endogenous secretions, and endogenously secreted Zn is a primary means of Zn homeostasis. This study examined whether B/P fluid alters the absorption/reabsorption of Zn and, in doing so, whether this contributes to homeostatic control of Zn. Animal experiments utilized rats fed 10 or 300 micrograms Zn/kg diet. An open-ended gut perfusion study in which 65Zn-labeled B/P fluid or 67Zn-labeled and digested diet found significantly decreased Zn absorption from B/P fluid. Although Zn absorption from both sources was less in animals fed diets higher in Zn, there was no interaction of treatment and diet. Further studies utilizing cultured human colon carcinoma cells (CACO-2) as in vitro models of gut enterocytes found that the presence of B/P fluid significantly decreased Zn retention and/or transport and resulted in a redistribution of cellular Zn after 1200 min of incubation. These studies show that a substance in B/P fluid can decrease the absorption of Zn and also suggest that dietary Zn and Zn associated with B/P secretions are absorbed from distinct pools. However, the lack of an interactive effect with diet, and the amount of time required to see differences in CACO-2 cells, suggest that differences in absorption are not a major contributor to Zn homeostasis. PMID- 7981008 TI - Fluctuations in Fe, Cu, Zn, Br, As, Se, and Rb concentrations in C57L/J mice bearing BW7756 murine hepatoma using radioisotope-induced X-ray fluorescence. AB - The effects of selenite or selenate supplementation on the concentration and distribution of Fe, Cu, Zn, As, Br, and Rb are investigated using the radioisotope-induced X-ray fluorescence, RIXRF. These effects are studied in the animals bearing BW7756 murine hepatoma and healthy animals for both of the oxidation states. Selenite and selenate induce different effects on the distribution of selenium, zinc, copper, bromine, and rubidium. The differences may be attributed to the differences in the inter element interaction after absorption into the bloodstream as well as to the mode of their intestinal absorption. Simultaneous supplementation of copper with selenite or selenate at the described levels has a profound influence on the concentration levels of other elements in the normal as well as in the diseased mice. The administration of selenium (0.67 micrograms/g body wt sodium selenite or sodium selenate, daily) and selenium and copper (0.67 and 1.35 micrograms/g body wt, respectively) has no effect on the incidence rate of hepatoma development. PMID- 7981009 TI - The effects of lower than conventional doses of oral nadolol on relative beta 1/beta 2-adrenoceptor blockade. AB - 1. The aim of the present study was to evaluate the relative beta 1/beta 2 antagonist selectivity of the beta-adrenoceptor blocker nadolol, in lower than conventional clinical doses. 2. Eight normal volunteers received single oral doses of either placebo (PL), nadolol 5 mg (N5), 20 mg (N20) or 80 mg (N80) in a single-blind, randomised crossover design. beta 1-adrenoceptor antagonism was assessed by attenuation of exercise tachycardia, and beta 2-adrenoceptor blockade by effects on salbutamol-induced chronotropic, hypokalaemic and finger tremor responses. The relative percentage attenuation of beta 2 and beta 1-mediated responses was calculated and expressed as beta 2:beta 1 selectivity ratios. 3. Nadolol produced dose-related reductions in exercise tachycardia in keeping with increasing beta 1-adrenoceptor blockade; mean % reduction (95% CI) compared with placebo: N5 10.7 (6.6 to 14.8), N20 21.4 (17.3 to 25.4), N80 38.9 (34.8 to 42.9). However, even the lowest dose of nadolol (5 mg) produced almost complete blunting of beta 2-mediated effects and significantly increase exercise hyperkalaemia; peak exercise hyperkalaemia (mmol l-1) (means and 95% CI): PL 4.88 (4.68 to 5.07), N5 5.36 (5.17 to 5.55), N20 5.48 (5.28 to 5.67), N80 5.42 (5.22 to 5.61). beta 2:beta 1 selectivity ratios significantly increased as the dose of nadolol was reduced. 4. These data suggest that whereas in the clinical dose range nadolol behaves as a non-selective beta-adrenoceptor antagonist, as the dose is reduced this drug demonstrates an increasing degree of selectivity for the beta 2 adrenoceptor.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7981010 TI - Reproducibility of non-invasive measurement and of short-term variability of blood pressure and heart rate in healthy volunteers. AB - 1. Spectral analyses of blood pressure and heart rate oscillations are increasingly used to assess the influences of diseases and drugs on the autonomic nervous system. Such influences can only be interpreted in view of the spontaneous variability of these oscillations. We therefore studied the reproducibility of power spectral analyses of blood pressure and heart rate fluctuations measured by a non-invasive finger plethysmographic method in 24 healthy volunteers. 2. Intra-observer reproducibility was assessed from measurements obtained on 3 consecutive days and 1 month later in each subject. Inter-observer reproducibility was assessed by comparing measurements made by two observers on one occasion. 3. There was no significant difference in standard haemodynamic and spectral analysis parameters (low frequency: 60-130 mHz and high frequency: respiration rate +/- 30 mHz) measured on 3 consecutive days and 1 month later in each subject. The standard deviation of differences between systolic blood pressure or heart rate oscillations on different occasions was in the 150-200 and 50-100 mm Hg Hz-1/2 or beats min-1 Hz-1/2 range for low frequency and high frequency oscillations respectively. Similar results were found when inter-observer reproducibility was considered. 4. From these results, we derived a sample-size table giving the number of subjects to be included in studies of cross-over or parallel design in order to detect a non-random difference in spectral analysis parameters.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7981011 TI - Haemodynamic response and pharmacokinetics after the first dose of quinapril in patients with congestive heart failure. AB - 1. Twenty-four elderly patients with stable, chronic congestive heart failure, NYHA II-IV, requiring addition of an ACE inhibitor to their existing therapy were randomised to receive double-blind a single dose of quinapril 2.5 mg p.o. or matching placebo after 24-48 h supervised diuretic withdrawal. 2. The effect of treatment on resting supine blood pressure, heart rate, plasma angiotensin converting enzyme (ACE) and circulating plasma renin activity was compared between groups over the first 24 h after dosing. The pharmacokinetic profiles of quinapril and the active metabolite quinaprilat were determined. 3. Compared with placebo, quinapril caused a statistically significant but modest fall in blood pressure from 3 to 10 h post dose. The maximum fall of 12 mm Hg (95% C.I. 5.4 18.5) was seen at approximately 5 h. Circulating ACE activity was 40% inhibited within 1 h. Maximum ACE inhibition (83.6%, 95% C.I. 76.7-90.5) was observed at 3 h. ACE remained 60% inhibited at 24 h post dose. tmax for quinapril was seen at 2.6 +/- 1.2 h. while tmax for quinaprilat was at 3.6, +/- 0.8 h. 4. Treatment with quinapril was associated with a significant rise in plasma renin activity (PRA) of 8.83 ng AI ml-1 h-1 (95% C.I. 0.30-17.96) compared with placebo. 5. Compared with placebo, quinapril 2.5 mg inhibits plasma ACE by over 60% for 24 h and reduces blood pressure for at least 10 h in patients with stable, chronic congestive heart failure. The blood pressure fall, although moderate and well tolerated, is more sustained than previously described for quinapril in heart failure. PMID- 7981012 TI - Pharmacokinetics of the enantiomers of bupivacaine following intravenous administration of the racemate. AB - 1. The pharmacokinetics of R(+)-bupivacaine and S(-)-bupivacaine were investigated following a 10 min intravenous infusion of the racemate (dose 30 mg) in 10 healthy males. 2. The fractions unbound of R(+)- and S(-)-bupivacaine in pre-dose plasma were determined for each subject after in vitro addition of rac bupivacaine (concentration of each enantiomer: approximately 300 ng ml-1). 3. The total plasma clearance of R(+)-bupivacaine (mean +/- s.d.: 0.395 +/- 0.076 l min 1) was greater (P < 0.0001) than that of S(-)-bupivacaine (0.317 +/- 0.067 l min 1). The volumes of distribution of R(+)-bupivacaine at steady state (84 +/- 29 l) and during the terminal log-linear phase (117 +/- 47 l) were larger (P < 0.0002) than those of S(-)-bupivacaine (54 +/- 20 l and 71 +/- 34 l, respectively). The terminal half-life (210 +/- 95 min) and mean residence time (215 +/- 74 min) of R(+)-bupivacaine were longer than those of S(-)-bupivacaine (157 +/- 77 min, P < 0.01, and 172 +/- 55 min, P < 0.02, respectively). 4. The free percentage of R(+) bupivacaine (6.6 +/- 3.0 %) was greater (P < 0.0002) than that of S(-) bupivacaine (4.5 +/- 2.1 %). 5. The plasma clearance of unbound R(+)-bupivacaine (7.26 +/- 3.60 1 min-1) was smaller (P < 0.01) than that of S(-)-bupivacaine (8.71 +/- 4.27 l min-1). Volumes of distribution based on unbound R(+) bupivacaine concentrations (Vuss: 1576 +/- 934 l; Vu: 2233 +/- 1442 l) did not differ from those of S(-)-bupivacaine (Vuss: 1498 +/- 892 l; Vu: 1978 +/- 1302 l). 6. The enantioselective systemic disposition of bupivacaine can to a large extent be attributed to differences in the degree of plasma binding of the enantiomers. PMID- 7981013 TI - Diazepam metabolism by human liver microsomes is mediated by both S-mephenytoin hydroxylase and CYP3A isoforms. AB - 1. The primary metabolism of diazepam was studied in human liver microsomes in order to investigate the kinetics and to identify the cytochrome P450 (CYP) isoforms responsible for the formation of the main diazepam metabolites, temazepam and N-desmethyldiazepam. 2. The formation kinetics of both metabolites were atypical and consistent with the occurrence of substrate activation. A sigmoid Vmax model equivalent to the Hill equation was used to fit the data. The degree of sigmoidicity was greater for temazepam formation than for N desmethyldiazepam formation, so that the ratio of desmethyldiazepam:temazepam formation increased as the substrate (diazepam) concentration decreased. 3. alpha Naphthoflavone activated both reactions but with a greater effect on temazepam formation than on N-desmethyldiazepam formation. In the presence of 25 microM alpha-naphthoflavone the kinetics for both pathways were approximated by Michaelis-Menten kinetics. 4. Studies with a series of CYP isoform selective inhibitors and with an inhibitory anti-CYP2C antibody indicated that temazepam formation was carried out mainly by CYP3A isoforms, whereas the formation of N desmethyldiazepam was mediated by both CYP3A isoforms and S-mephenytoin hydroxylase. PMID- 7981015 TI - Lack of pharmacokinetic interaction between vinpocetine and oxazepam. AB - The influence of multiple doses of vinpocetine (10 mg three times daily) on the steady state plasma concentrations of oxazepam (10 mg three times daily) was studied in 16 healthy subjects. The mean (+/- s.d.) AUC (ng ml-1h-1) of oxazepam over 24 h during combined treatment was 4716 +/- 2296 and for oxazepam treatment alone it was 4737 +/- 2448 (95% confidence intervals for ratio of means = 95.4 103.7%). The degree of plasma protein binding of oxazepam was 98.11 +/- 0.32% and was not affected by vinpocetine. Independent of vinpocentine treatment a significant diurnal change in the plasma binding of oxazepam was observed; the free drug fraction was 20% higher during the night than during the day. Cmax and AUC values based on total oxazepam in plasma were 10% lower during the night. The results indicate a lack of influence of vinpocetine on oxazepam kinetics. Diurnal changes in the plasma binding of oxazepam probably have no clinical consequences. PMID- 7981014 TI - The effects of angiotensin II on circulating levels of natriuretic peptides. AB - We have evaluated the differential release of A, B and C-type natriuretic peptides in response to incremental doses of angiotensin II (2, 4 and 6 ng kg-1 min-1). Baseline plasma concentrations of ANP (5.99 +/- 0.74 pmol 1-1) were significantly (P < 0.05) higher than BNP (1.53 +/- 0.48 pmol 1-1) or CNP (0.41 +/ 0.11 pmol 1-1). Angiotensin II infusion caused a significant (P < 0.05) increase in plasma ANP to 53.76 +/- 17.3 pmol 1-1 at 6 ng kg-1 min-1. Plasma concentrations of BNP and CNP were not significantly affected by angiotensin II. Arterial blood pressures and systemic vascular resistance increased (P < 0.001) in response to angiotensin II infusion. Thus, ANP, unlike BNP or CNP, is released acutely in response to the pressor stimulus of angiotensin II. This may represent a dissociation in release of the natriuretic peptides, in terms of short and long term responses to activation of the renin-angiotensin system. PMID- 7981017 TI - Influence of amesergide treatment on the dextromethorphan test. PMID- 7981016 TI - Formation and elimination of sulphamethoxazole hydroxylamine after oral administration of sulphamethoxazole. AB - The formation and elimination of sulphamethoxazole hydroxylamine in relation to the pharmacokinetics of the parent compound and its N4-acetyl metabolite were investigated in six healthy subjects after a single oral dose of 800 mg sulphamethoxazole. The apparent half-lives of sulphamethoxazole and its metabolites were approximately 10 h, indicative of formation rate-limited metabolism. The mean residence time of the hydroxylamine metabolite was 5.5 +/- 1.5 h. The renal clearance of sulphamethoxazole hydroxylamine was 4.39 +/- 0.91 l h-1. The urinary recovery of sulphamethoxazole accounted for 16.5 +/- 5.5% of the dose, N4-acetyl-sulphamethoxazole for 46.2 +/- 6.6% and the hydroxylamine metabolite for 2.4 +/- 0.8%. The remaining 35% of the dose was unaccounted for. Acetylator phenotype was determined using sulphadimidine. The renal excretion of sulphamethoxazole hydroxylamine was 1.9 +/- 0.9% in slow acetylators (n = 3) and 2.8 +/- 0.3% in fast acetylators (n = 3); for N4-acetyl-sulphamethoxazole the values were 48 +/- 6% and 44 +/- 8%, respectively. Sulphamethoxazole is metabolized, although to a limited extent, to a hydroxylamine metabolite. This metabolite may be important for the pathogenesis of adverse reactions. PMID- 7981018 TI - Why the Safety Assessment of Marketed Medicines (SAMM) guidelines are needed. PMID- 7981019 TI - Guidelines for company-sponsored Safety Assessment of Marketed Medicines (SAMM) guidelines. Medicines Control Agency, Committee on Safety of Medicines, Royal College of General Practitioners, British Medical Association and Association of the British Pharmaceutical Industry (November 1993) PMID- 7981020 TI - A novel index for expressing exposure of the infant to drugs in breast milk. AB - 1. We present a novel index for expressing the exposure of the infant to drugs in breast milk, which unifies two independent factors: a pharmacokinetic parameter, drug clearance, and a physiochemical parameter, i.e. milk-to-maternal plasma drug concentration ratio (M/P ratio). 2. During breast-feeding by a woman receiving therapeutic doses of a drug at steady state this index is given by: Exposure index = A x (M/P ratio)/CLI where A is a coefficient (10 ml kg-1 min-1) and CLI is drug clearance in the infant (ml kg-1 min-1). 3. This equation indicates a hyperbolic relationship between drug clearance and the exposure level of the breast-fed infant at a given M/P ratio of drug, emphasizing the importance of drug clearance as a determinant of infant exposure. PMID- 7981022 TI - Arthritis prevalence and activity limitations. 1990. PMID- 7981021 TI - Expanded programme on immunization. Status of poliomyelitis eradication in the WHO European Region. PMID- 7981023 TI - Plague. India. PMID- 7981024 TI - Experimental embryology in Japan, 1930-1960. A historical background of developmental biology in Japan. PMID- 7981025 TI - A view of amphibian embryology research in Japan through the scientific biography of Professor Osamu Nakamura. Interview by Makoto Asashima. PMID- 7981026 TI - Egg-jelly signal molecules for triggering the acrosome reaction in starfish spermatozoa. AB - It was in the early 1950s that J.C. Dan discovered the acrosome reaction in sea urchins, starfishes and several other marine invertebrates at Misaki Marine Biological Station on the Pacific coast of Japan. We now know that in many animals including mammals the acrosome reaction is an essential, and probably the most central, change in spermatozoa for fertilization. Starfish spermatozoa undergo the acrosome reaction upon encountering the jelly coat consisting of glycoproteins, steroid saponins, oligopeptides and inorganic components. To induce the acrosome reaction, three egg jelly components act in concert on the spermatozoa: a highly sulfated glycoprotein named acrosome reaction-inducing substance (ARIS), a group of sulfated steroidal saponins named Co-ARIS, and a group of glutamine-rich tetratriacontapeptides named sperm activating peptide (SAP). The action of ARIS is quite species-specific due to the specificity of ARIS-receptors in a restricted domain of the sperm surface and depends very much on sulfated saccharide chains. Co-ARIS is not much species-specific and its action depends on the sulfate group and steroid side chain. SAPs have a ring of 25 residues and increase the intracellular pH of spermatozoa. None of them can induce the acrosome reaction by itself in normal sea water, but ARIS does induce it in high Ca2+ or high pH sea water. Although a combination of ARIS and either Co-ARIS or SAP induces the acrosome reaction in normal sea water, all three are required to mimic the full activity of dissolved jelly coat. PMID- 7981027 TI - Early events in the histo- and cytogenesis of the vertebrate CNS. AB - Development of the vertebrate, viewed on the cellular level, proceeds by sequential steps in which potencies of progenitor cells become progressively and irreversibly restricted. This is known as progression of the major differentiation. Cytogenesis of the CNS may be regarded as one typical example. The period of cytogenesis in the CNS is divided into three consecutive stages. In stage I, the wall of the neural tube is composed solely of matrix cells. In stage II, i.e., the stage of neuronogenesis, some of the daughter matrix cells are determined at the early G1 phase to be differentiated into neuroblasts. The specificity of individual neurons appears to be irreversibly determined at the time of birth of the neuroblasts, as a function of time-and-place of their production. The individual matrix cells that have existed at the very beginning of neurogenesis give birth to a series of progressively different types of neurons in stage II as the major differentiation proceeds. Finally, matrix cells cease to produce neurons. This is the end of stage II. Thereafter, only non neuronal cells, namely neuroglia and ependymal cells, are produced. This is stage III or the stage of neuroglia production. The sequential nature of the differentiative behavior of matrix cells can be explained by the hypothesis of progressive gene inactivations that accumulate in genomes of matrix cells during development. Different types of neurons are produced from matrix cells at different states of the "major differentiation".(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7981028 TI - Cell reproduction: induction of M-phase events by cyclin-dependent cdc2 kinase. AB - Although a major concern in the development of multicellular organisms is cell differentiation, the construction of a multicellular system essentially depends on cell multiplication, which consists of genomic duplication and segregation. Recent progress has revealed that cyclin-dependent kinases (CDKs) are key components of a cell cycle engine that governs cell proliferation. This article focuses on how CDKs induce M-phase events characterized by nuclear membrane breakdown, chromosome condensation and mitotic spindle formation to assure genomic segregation. PMID- 7981029 TI - Initiation and stimulation of spermatogenesis in vitro by mammalian follicle stimulating hormone in the Japanese newt, Cynops pyrrhogaster. AB - In order to elucidate the molecular mechanisms by which spermatogenesis is regulated, especially the roles of hormones and somatic cells in the initiation and promotion of spermatogenesis, we developed an organ culture system with a chemically defined medium. When newt testes fragments rich in secondary spermatogonia were cultured in control medium for three weeks, most of the testicular cysts still remained as secondary spermatogonia. On the other hand, in the medium supplemented with follicle-stimulating hormone (FSH) alone, DNA syntheses in secondary spermatogonia and Sertoli cells were stimulated and secondary spermatogonia differentiated into primary spermatocytes (zygotene pachytene) in more than half of the cysts by the second week. When newt testes fragments rich in primary spermatocytes were cultured in a control medium for three weeks only round spermatids were observed at the most advanced stage. On the other hand, in the medium supplemented with FSH alone, elongated spermatids appeared by the second week. Neither the addition of luteinizing hormone (LH) nor androgens (testosterone and 5 alpha-dihydrotestosterone) to the control medium stimulated differentiation for either step. Consistent with these findings was the fact that radioreceptor assays revealed high affinity specific binding sites for FSH but none for LH for either stage of the testes (secondary spermatogonia and primary spermatocytes). Preliminary results indicate that FSH does not bind to germ cells but to somatic cells (most probably Sertoli cells). These and our unpublished data suggest that FSH triggers proliferation and differentiation of spermatogonia into elongated spermatids by acting on Sertoli cells which in turn act on germ cells. PMID- 7981030 TI - Remodeling of sperm chromatin induced in egg extracts of amphibians. AB - Sperm nuclear basic proteins of Bufo japonicus consist of 2 distinct protamines, whereas those of Xenopus laevis consist of 6 sperm-specific basic proteins (SP1 6) in addition to H3, H4 and smaller amounts of H2A and H2B. Cloning of pertinent cDNAs and partial amino acid sequence studies suggested that these 6 sperm specific proteins of Xenopus are encoded by 3 distinct genes. Despite differences in their initial compositions of chromatin, sperm nuclei exposed to amphibian egg extracts rapidly decondense, lose sperm-specific basic proteins, and concomitantly form an ordinary nucleosome core consisting of H2A, H2B, H3, H4, and cleavage-stage specific subtype H1X. In this remodeling process, nucleoplasmin plays dual roles as a molecular chaperone, selectively removing sperm-specific basic proteins from, and bringing H2A and H2B to, sperm DNA. Thus remodeling of chromatin is induced even in mammalian (human) sperm nuclei under defined conditions including nucleoplasmin and exogenous histones. PMID- 7981031 TI - Endocrine regulation of gametogenesis in fish. AB - The pituitary-gonadal axis plays an important role in regulating gametogenesis in vertebrates. In most cases, gonadotropins act through the biosynthesis of gonadal steroid hormones which in turn mediate various stages of gametogenesis. A series of studies in our laboratory using several species of teleost fishes as experimental animals has provided new information about the endocrine regulation of gametogenesis, including oocyte growth, oocyte maturation, spermatogenesis and sperm maturation. This article briefly reviews our findings on the identification of steroidal mediators involved in each process of gametogenesis, and the sites and mechanisms of action of the mediators. These observations collectively demonstrate the appropriateness of using teleost fishes as valid models for examining hormonal influences on gametogenesis. Such models could also have applications and validity for vertebrates in general. PMID- 7981032 TI - Genes that are involved in Bombyx body plan and silk gene regulation. AB - I have summed up how silk gene regulation studies in Bombyx mori have been carried out. This process has brought me naturally to realize the importance of understanding the Bombyx body plan in comparison with the body plans of other organisms. Although their current status remains preliminary, I have tried to summarize the ongoing projects and to reveal future problems to be answered. PMID- 7981033 TI - Allorecognition in compound ascidians. AB - In botryllids (colonial ascidians), there are two types of allorecognition: colony specificity and colony resorption. Colony specificity is manifested by fusion and rejection between two conspecific colonies. The genetic basis for this colony specificity resides in a single highly polymorphic gene locus (fusibility locus) with codominantly expressed alleles. Two colonies with no alleles in common at this locus reject each other, whereas colonies sharing at least one allele at the fusibility locus fuse and form a chimera. That is, in colony specificity, self components are distinguished from nonself components, and failure to recognize self induces rapid rejection reactions. The process of rejection in colony specificity is not uniform among all botryllid ascidians. Colony resorption can occur after the establishment of fusion between two colonies. Zooids of one partner of a chimera are resorbed more than 1 week after fusion, or, by amputation of fused blood vessels, the chimera becomes separated into the two original colonies. Colony resorption is also controlled mainly by the fusibility locus. It usually occurs in a chimera between two colonies sharing only one allele at this locus. In colony resorption, nonself determinants are recognized and chronic rejection reactions are induced resembling MHC-dependent graft rejection. Based on these findings, the fusibility locus of botryllids seems to be very similar to the MHC of vertebrates. Considering that vertebrates evolved directly from ascidians, it is likely that the fusibility locus is an ancestral form of the vertebrate MHC. PMID- 7981034 TI - Control of cell differentiation and morphogenesis in amphibian development. AB - We reviewed cell differentiation and morphogenesis by mesoderm-inducing factors during amphibian embryogenesis. Recently, two kinds of growth factors, activin and FGF, have been identified as influential candidates for natural mesoderm inducing factor in amphibian development. These factors are present in early Xenopus embryos. In particular, activin has been shown to induce many kinds of mesodermal tissues in a dose-dependent manner. Activin-treated ectodermal sheet (animal cap) acts as an organizer causing gene expression, mesoderm formation and functional events such as secondary axis formation. Follistatin, an activin specific binding protein, also present in the early Xenopus embryo, makes a complex with activin. Follistatin protein exerts no inducing activity of Xenopus animal cap. Endogenous follistatin may, however, play the role of an activin regulation factor. Endogenous actions of activin and FGF were studied using injection of their receptor mRNAs. Disruption of the FGF signaling pathway by its non-functional dominant negative receptors produced trunk and tail defects. In the case of activin, an embryo cannot form axial structures. Animal-half blastomeres from the late 8-cell stage Xenopus embryo respond to activin, and there are prepatterns in ventral and dorsal cells from very early stages. The timing of mesoderm induction during development and the relationship between the inducing factors and competent cells are discussed in this report. Differentiation of tissues and organized formation of organs can be understood as a system of serial inductive reactions originating from the organizer. We have attempted to construct a model of organizer formation based on the results of recent studies. PMID- 7981035 TI - Aspects of morphogenesis and cytodifferentiation of endoderm offered by organ culture techniques. AB - In this article, I will summarize the results obtained in my laboratory from the study of organogenesis since 1970. The results have shown region-specific directive influence of mesenchymes and reactivity of endoderms including those of the allantois, yolk sac, digestive tract and urogenital sinus. It was also shown that morphogenesis can take place without coupling cytodifferentiation in heterologous recombination experiments. PMID- 7981036 TI - Rostrocaudal polarity formation of chick optic tectum. AB - The optic tectum receives retinal fibers in a topographically ordered manner. For the formation of the precise connections, the tectum is believed to be positionally specified by gradients of molecules along axes. Rostrocaudal polarity of the tectum is first detectable at embryonic day 2 (E2) in the chick, by the caudorostral gradient of en expression, then by the rostrocaudal gradient of cytoarchitectonic development. Tectum rotation experiments showed that tectum rostrocaudal polarity is not determined at around 10-somite stage, but is fixed on E3. Ectopic tectum was produced in the diencephalon by transplanting the mesencephalic alar plate heterotopically. In the ectopic tectum, en expression was weakest at the caudal (nearest to the host diencephalo-mesencephalon junction) and strongest at the rostral end. Consequently, the pattern of en expression in the host and ectopic tecta was nearly a mirror image. Retinal fibers projected to the ectopic tectum in a topographic order in accordance with the inverted gradient of the en expression pattern. Ectopic tecta was also produced by heterochronal transplantations between E3 host and E2 donor, where the en pattern was preserved. Retinotectal projection pattern was also preserved, suggesting that en expression patterns are followed by retinotopic order with regard to rostrocaudal polarity. PMID- 7981037 TI - Mechanisms of the proliferation and differentiation of plant cells in cell culture systems. AB - Plant cell functions have been investigated in various cell culture systems. In this review, we summarize results obtained from investigations of gene expression during the cell cycle in synchronized cultures of Catharanthus roseus during somatic embryogenesis in suspension cultures of Daucus carota, during organogenesis in tissue cultures of Arabidopsis thaliana and during the transdifferentiation of isolated mesophyll cells to tracheary elements in single cell cultures of Zinnia elegans. PMID- 7981038 TI - The brain secretory peptides that control moulting and metamorphosis of the silkmoth, Bombyx mori. AB - Progress made toward the elucidation of molecular features of the prothoracicotropic hormone (PTTH) of the silkmoth Bombyx mori is reviewed. PTTH stimulates the prothoracic glands to synthesize and release ecdysone, and is therefore a key hormone for the regulation of insect moulting and metamorphosis. Bombyx PTTH is a 30 kDa homodimeric glycoprotein, whose carbohydrate moiety is not essential for the biological function. The Bombyx genome contains a single copy of the PTTH gene. PTTH is produced by four dorsolateral neurosecretory cells of brain. Another Bombyx brain peptide exerting prothoracicotropic activity to a heterologous moth Samia cynthia ricini but no activity to Bombyx has been identified and termed bombyxin. Bombyxin is a 5 kDa heterodimeric peptide that shows a high similarity to insulin in the amino acid sequence. The bombyxin gene structure also shows a high similarity with the insulin gene structure. The Bombyx genome contains more than 30 copies of the bombyxin gene. Bombyxin is synthesized by eight dorsomedial neurosecretory cells of brain. PMID- 7981039 TI - Regulation of cell differentiation and pattern formation in Dictyostelium development. AB - Free-living cells of Dictyostelium discoideum aggregate to form a slug-shaped cell mass and differentiate into prestalk and prespore cells. The differentiation of prespore cells is characterized by expression of Dp87 gene, the earliest event of prespore differentiation. It encodes a protein which first appears in ER of aggregating cells in a precursor form, is then translocated to prespore vacuoles and modified to a mature form and finally exocytosed to constitute the sorus matrix. The transcription of Dp87 is regulated by the cis-acting region consisting of positive, prespore-specific, negative, non-prespore-specific and positive, cell-type-non-specific elements. Cells expressing Dp87 appear at random in early aggregation streams and centers and then sort out to the posterior part of the slug. Intercellular signals required for prestalk and prespore differentiation were investigated by incubation at a low cell density of disaggregated cells. cAMP is inhibitory at the first and second stages of prespore differentiation, while it is required at the third stage. The stalk differentiation is divided into four stages: cAMP is required at the second stage and differentiation inducing factor (DIF) at the third stage, where a low molecular weight secretory substance is also required. At the third stage, cAMP inhibits both ecmA and ecmB expression, while 8-Br-cAMP specifically induces ecmB and maturation of prestalk to stalk cells. The relationship between the differentiation tendency of preaggregative cells and the cell-cycle phase at the initiation of development was studied by the use of cells synchronized for growth by a temperature-shift method.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7981040 TI - Genes involved in the dedifferentiation of plant cells. AB - Since the initial process of culturing tobacco mesophyll protoplasts can be considered as a model system of dedifferentiation of higher plants, the mode of expression of genes induced by auxin, a key factor in inducing dedifferentiation, has been analyzed during the regaining of meristematic activity of quiescent and differentiated tobacco mesophyll. By differential screening we have isolated three auxin-regulated genes, which we named parA, parB and parC. parA and parC, which belong to the same gene family, were supposed to play a role in transcriptional regulation upon induction by auxin, while parB encoded glutathione S-transferase. Although it was supposed that the expression of these par genes should play a pivotal role in regaining the meristematic activity of the differentiated tobacco mesophyll cells, a possibility that other less abundantly expressing genes would have been neglected in these studies has not been excluded. On the other hand, the search for genes which would be involved in maintaining cell division activity in the dedifferentiated plant cells allowed us to isolate a few genes. One of these genes, designated arcA, belonged to a beta subunit-like protein of heterotrimeric G proteins. The significance of the involvement of this gene product in maintaining the meristematic activity of plant cells cultured in vitro has been discussed. PMID- 7981041 TI - Multiple functions of raf proto-oncogene during development from analysis of a temperature-sensitive mutation of Drosophila. AB - A temperature-sensitive (ts) mutation of Drosophila melanogaster for D-raf, encoding a serine/threonine protein kinase, was newly induced by EMS-treatment. Temperature-shift experiments on the ts mutant revealed that D-raf is required during most of the developmental stages, and confirmed the previously reported roles of D-raf in the regulation of cell proliferation and in the determination of cell fates at terminal regions of the embryo (Nishida et al., EMBO J. 7:775 781, 1988; Ambrosio et al., Nature 342:288-291, 1989a). Detailed analysis of cell proliferation demonstrated the role of D-raf at other than M-phase in cell cycle. TSP analysis during pupal stages revealed yet another role of D-raf in eclosion. Mosaic analysis of an eclosion-defective hypomorphic mutation revealed the tissue responsible for this defect to be the muscle and/or nervous system in the thorax. Molecular lesion associated with the ts mutation was found to be an alteration of an amino acid residue in a highly conserved region that defines the kinase subdomain VIII. Molecular analysis of null mutations also suggested the importance of the kinase domain for the biological functions of D-raf. Elucidation of the multi-functional nature of signal transducers is of great importance for our understanding of the molecular mechanisms of development, and the ts mutation for pleiotropic D-raf obtained in this study promises to be useful for dissecting signal transduction pathways during development. PMID- 7981042 TI - A long polypyrimidine:polypurine sequence in 5' flanking region of arylsulfatase gene of sea urchin embryo. AB - Sea urchin (Hemicentrotus pulcherrimus) arylsulfatase(Ars) gene contains a long (622 bp) polypyrimidine:polypurine (Pyr-Pur) sequence in its 5' flanking region. The Pyr-Pur sequence inserted into a plasmid was sensitive to S1 nuclease at a low acidic pH (pH 5) when the plasmid was negatively supercoiled. From the distribution pattern of S1 sites in the Pyr-Pur region it is concluded that a (CT)11:(GA)11 tract in this region could adopt an unusual DNA configuration distinct from the usual B-form. Another feature of the Pyr-Pur sequence is that this (CT)11:(GA)11 tract is sandwiched by two oligo(dC):oligo(dG) stretches (G strings) that are located at almost an equal distance from both ends of the (CT)11:(GA)11 tract. Mobility shift assay and DNase-I footprinting revealed that the gastrula nuclei contain nuclear proteins that interact with two distinct oligo(dG):oligo(dG) tracts (G-strings) in the Pyr-Pur region. The possibility is suggested that G-strings may be related to formation and stabilization of an unusual DNA configuration of a (CT)11:(GA)11 tract. PMID- 7981043 TI - Regionally and hormonally regulated expression of genes of collagen and collagenase in the anuran larval skin. AB - The skin of an anuran tadpole undergoes region-dependent metamorphic changes: the body (head and body trunk) transforms into the adult type, while the tail falls into programmed cell death. The present study was undertaken to investigate the regional specificity of metamorphosis at a molecular level, focusing on genes of collagen and collagenase that are known to be activated in their synthesis at metamorphosis. A cDNA probe utilized for collagen was Hf677 (a clone of human type I collagen alpha 1 chain). A probe for collagenase gene was cloned in the present study from a cDNA library of bullfrog tadpole skin, characterized and named Tc1. Tc1 contained the consensus sequence of zinc-metalloproteinases and showed a high homology to mammalian collagenases. Using these recombinant DNAs as probes, RNA blot analyses were performed for the body and tail skin of tadpoles that had been in spontaneous metamorphosis, induced to metamorphosis by the injection of thyroid hormone, or had been induced to grow by prolactin treatment. Collagenase gene was activated irrespective of regions of the skin, body or tail at the early metamorphic climax stage, although the extent of activation was region-dependent. In contrast, metamorphic changes of collagen gene expression showed a clear regional dependency. The transcription level in body skin was enhanced at the onset of metamorphosis while that in tail skin was markedly suppressed. Thyroid hormone was shown to be responsible for this region-dependent expression of collagen genes at metamorphosis. Prolactin, a suppressor hormone of amphibian metamorphosis, enhanced the transcription of collagen genes and suppressed that of collagenase.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7981044 TI - Sorting out of limb bud cells in monolayer culture. AB - To examine differences in the surface properties of limb bud cells, we mixed cells from the progress zone at different stages or from different positions along proximodistal axis of chick and quail wing limb buds. To identify the origin of cells, a chick-specific antibody was used in a mixed culture of chick and quail cells, or cells from one of the stages were labeled with a fluorescent dye, PKH-26. Within 18 hours in mixed culture, cells segregated from each other and formed patches of various sizes. The process zone cells at early developmental stages mixed homogeneously with the cells from proximal region of old limb buds and the progress zone cells at late stages mixed homogeneously with the cells from distal region of the old limb buds. These results suggest that surface properties of cells in progress zone change during limb bud development and vary along the proximodistal and anteroposterior axes of the limb bud and that these differences in surface property may correspond to the positional values for limb pattern formation. PMID- 7981045 TI - The loss of gap junctional cell-to-cell communication is coupled with dedifferentiation of retinal pigmented epithelial cells in the course of transdifferentiation into the lens. AB - Retinal pigmented epithelial cells (PECs) of the chick embryo can be cultured as a monolayer of melanized hexagonal cells. Modifications of the culture condition make the cells lose most of the phenotypes and further transdifferentiate into lentoid bodies within a few weeks. Ultrastructural observations showed that PECs and the lentoids have gap junctions with distinct morphology. Diffusion of a fluorescent dye confirmed the presence of gap junctions in both phenotypes. However, cells in the intermediate stage of transdifferentiation, which show neither the phenotype of the PEC nor that of the lentoid and are called dedifferentiated PECs here, have almost no gap junction structure. We propose the possibility that the dedifferentiation of PECs and the loss of cell-to-cell communication are tightly coupled events. This cell culture system is a suitable material for further studying this relationship by cellular and molecular approaches. PMID- 7981046 TI - Lens-specific activity of the chicken delta 1-crystallin enhancer in the mouse. AB - A lens-specific enhancer was identified in the third intron of the chicken delta 1-crystallin gene by analysis based on transient transfection of primary-cultured cells. To assess the significance of this enhancer's activity in embryonic lens cells during development, tkCAT gene carrying the enhancer was introduced into mouse embryos utilizing ES (embryonic stem) cell-mediated gene transfer. In the undifferentiated culture condition, ES lines with enhancer-carrying tkCAT did not express any significant level of CAT (chloramphenicol acetyltransferase). However, when the ES cells were injected into a blastocyst and allowed to differentiate into various somatic cells of an embryo, CAT expression was observed exclusively in lens, and the expression was dependent upon the delta 1 crystallin enhancer. We concluded that the delta 1-crystallin enhancer alone is sufficient for eliciting lens-specific gene expression in developing mouse embryos and that the mechanism of lens-specific regulation effected by the delta 1-crystallin enhancer is conserved between the chicken and the mouse. PMID- 7981047 TI - Transdifferentiation of pigmented multipotent epithelium during morphallactic development of budding tunicates. AB - In the budding tunicate, Polyandrocarpa misakiensis, the atrial epithelium is the major formative tissue giving rise to the pharynx, digestive tract, brain and endostyle of a bud. We show here that this multipotent epithelium carries several differentiation markers that are lost in the process of bud development. In both adult animals and growing buds, the atrial epithelium contained orange-pigmented granules in the cytoplasm. In developing buds, on the other hand, the cells committed to organ primordia have lost the granules, taken a cuboidal shape and have a large nucleus with a prominent nucleolus, like undifferentiated cells. The atrial epithelium was also characterized by ALP expressed on the apical surface of the cell. During budding the enzyme activity disappeared from the atrial epithelium and reappeared in the primordial digestive tract. Immunohistochemical studies suggested strongly that during gut formation, ALP antigens has been switched from the epithelial isoform to the intestinal isoform. These results have shown that in P. misakiensis budding involves transdifferentiation of multipotent, but differentiated epithelium, confirming our previous results (Fujiwara and Kawamura, Dev. Growth Differ. 34:463-472, 1992). PMID- 7981048 TI - Differential expression of alpha N-catenin and N-cadherin during early development of chicken embryos. AB - alpha-Catenins are a group of proteins associated with cadherin cell-cell adhesion molecules, and play indispensable roles in the function of the cadherins. alpha N-catenin, a subtype, was identified as a protein associated with N-cadherin. In this study, we investigated the expression pattern of alpha N catenin in early chicken embryos, and compared it with that of N-cadherin. alpha N-catenin was first detected in the closed somites and neural tube, and, at later stages, in many other tissues including the central nervous system (CNS), skeletal muscles, various regions of the overlying ectoderm, and some endodermal layers. In the CNS and skeletal muscles, both alpha N-catenin and N-cadherin were strongly expressed, and their distribution patterns were similar. However, in some parts of the ectoderm and endoderm, only alpha N-catenin was expressed. On the other hand, various mesenchymal tissues and peripheral nerves strongly expressed N-cadherin, but their alpha N-catenin expression was, in general, weak. Thus, the expression of these two proteins did not always correlate with each other. These results suggest that cells use different combinations of a cadherin and an alpha-catenin in a tissue-specific manner. PMID- 7981049 TI - Strain difference in establishment of mouse embryonic stem (ES) cell lines. AB - For utilization of the mouse embryonic stem (ES) cells for various purposes, it is desirable that the cell lines are established from various sources such as inbred and mutant mouse strains. So far, however, most ES cell lines used in genetic manipulation have been derived from the 129/Sv strain. We have established ES cell lines from blastocysts of the C57BL/6 strain at high efficiency by use of a fibroblast cell line SL10 as feeder cells, and supplementing the culture medium with 5,000 unit/ml LIF. Using such culture conditions, we have also established a number of ES cell lines from the BALB/c, BXSB/MpJ-Yaa and MRL/Mp-lpr/lpr mouse strains. Procedure for establishment of ES cell lines had to be modified among the mouse strains, indicating the strain difference. For example, only a few stem cell colonies appeared from the BALB/c blastocysts. Stem cells of the BXSB strain were very sensitive to the trypsinization in subculturing. Most of these cell lines had normal karyotype and produced chimeric mice. Several C57BL/6 cell lines contributed to the germ-line. These results indicate that ES cell lines can be established from various mouse strains, but their characteristics are different among strains. PMID- 7981050 TI - Predominant melanogenesis and lentoidogenesis in vitro from multipotent pineal cells by dimethyl sulfoxide and hexamethylene bisacetamide. AB - Pineal cells of the 8-day embryonic quail are multipotent cells which differentiate in vitro into skeletal muscle fibers, pigmented epithelial cells (PECs), lens cells and neurons. However, it was not yet clear whether precursor cells which gave such a wide repertoire of differentiation were single type or not. The present culture studies revealed that pineal cells were exclusively directed to ocular differentiation pathways by dimethyl sulfoxide (DMSO) and hexamethylene bisacetamide (HMBA), suggesting a single type of precursor cell in the pineal body. DMSO directed pineal cells to differentiate into PECs. Co administration of basic fibroblast growth factor (bFGF) with DMSO partially inhibited PEC differentiation and promoted lens cell differentiation. Northern blot analysis using cDNAs specific to PEC and lens cell confirmed this morphological observation. HMBA completely inhibited pigmentation of cultured pineal cells and markedly promoted lens cell differentiation. Ocular differentiation of pineal cells was accompanied with the loss of myogenicity. We discuss three possible pathways of lens cell differentiation from pineal cells. The agents which affect pineal cell differentiation seemed to modulate the cell substrate interaction. And the interaction was suggested to be one of the environmental cues in the differentiation. PMID- 7981051 TI - 5-En-androstene-3 beta,17 beta-diol inhibits the growth of MCF-7 breast cancer cells when oestrogen receptors are blocked by oestradiol. AB - Adrenal androgens show a dual and apparently opposite effect on the growth of oestrogen-responsive breast cancer: they stimulate growth on their own, but counteract the growth-stimulatory effect of oestrogens. Focusing on the inhibitory action we have studied the effects of 5-en-androstene-3 beta,17 beta diol (ADIOL) on the growth of oestrogen-responsive MCF-7 breast cancer cells in the presence of oestrogens (oestradiol and diethylstilboestrol), antiestrogens (tamoxifen) and antiandrogens (hydroxyflutamide). The inhibition of oestrogen stimulated growth, attained with nanomolar concentrations of ADIOL, was not modified by increasing concentrations of diethylstilboestrol up to 100 nM. This inhibition was counteracted by antiandrogens, which were unable to block the ADIOL stimulatory effect in steroid-free medium. On the other hand, in the presence of tamoxifen ADIOL showed an additive antiproliferative activity also in steroid-free medium, rather than the usual stimulatory effect. These results suggest that ADIOL stimulates breast cancer cell growth via oestrogen receptors, but inhibits oestrogen-stimulated growth via androgen receptors. PMID- 7981052 TI - Characterisation of tumour blood flow using a 'tissue-isolated' preparation. AB - Tumour blood flow was characterised in a 'tissue-isolated' rat tumour model, in which the vascular supply is derived from a single artery and vein. Tumours were perfused in situ and blood flow was calculated from simultaneous measurement of (1) venous outflow from the tumour and (2) uptake into the tumour of radiolabelled iodo-antipyrine (IAP). Comparison of results from the two measurements enabled assessment of the amount of blood 'shunted' through the tumours with minimal exchange between blood and tissue. Kinetics of IAP uptake were also used to determine the apparent volume of distribution (VDapp) for the tracer and the equilibrium tissue-blood partition coefficient (lambda). lambda was also measured by in vitro techniques and checks were made for binding and metabolism of IAP using high-pressure liquid chromatography. VDapp and lambda were used to calculate the perfused fraction (alpha) of the tumours. Tumour blood flow, as measured by IAP (TBFIAP), was 94.8 +/- 4.4% of the blood flow as measured by venous outflow, indicating only a small amount of non-exchanging flow. This level of shunting is lower than some previous estimates in which the percentage tumour entrapment of microspheres was used. The unperfused fraction ranged from 0 to 20% of the tumour volume in the majority of tumours. This could be due to tumour necrosis and/or acutely ischaemic tumour regions. For practical purposes, measurement of the total venous outflow of tumours is a reasonable measure of exchangeable tumour blood flow in this system and allows for on-line measurements. Tracer methods can be used to obtain additional information on the distribution of blood flow within tumours. PMID- 7981053 TI - Mononuclear cells contaminating acute lymphoblastic leukaemic samples tested for cellular drug resistance using the methyl-thiazol-tetrazolium assay. AB - The methyl-thiazol-tetrazolium (MTT) assay is a drug resistance assay which cannot discriminate between malignant and non-malignant cells. We previously reported that samples with > or = 80% leukaemic cells at the start of culture give similar results in the MTT assay and the differential staining cytotoxicity assay, in which a discrimination between malignant and non-malignant cells can be made. However, the percentage of leukaemic cells may change during culture, which might affect the results of the MTT assay. We studied 106 untreated childhood acute lymphoblastic leukemia (ALL) samples with > or = 80% leukaemic cells at the start of culture. This percentage decreased below 80% in 28%, and below 70% in 13%, of the samples after 4 days of culture. A decrease below 70% occurred more often in case of 80-89% leukaemic cells (9/29) than in case of > or = 90% leukaemic cells at the start of culture (5/77, P = 0.0009). Samples with < 70% leukaemic cells after culture were significantly more resistant to 6 out of 13 drugs, and showed a trend towards being more resistant to two more drugs, than samples with > or = 80% leukaemic cells. No such differences were seen between samples with 70-79% and samples with > or = 80% leukaemic cells after culture. We next studied in another 30 ALL samples whether contaminating mononuclear cells could be removed by using immunoamagnetic beads. Using a beads to target cell ratio of 10:1, the percentage of leukaemic cells increased from mean 72% (s.d. 9.3%) to mean 87% (s.d. 6.7%), with an absolute increase of 2-35%. The recovery of leukaemic cells was mean 82.1% (range 56-100%, s.d. 14.0%). The procedure itself did not influence the results of the MTT assay in three samples containing only leukaemic cells. We conclude that it is important to determine the percentage of leukaemic cells at the start and at the end of the MTT assay and similar drug resistance assays. Contaminating mononuclear cells can be successfully removed from ALL samples using immunomagnetic beads. This approach may increase the number of leukaemic samples which can be evaluated for cellular drug resistance with the MTT assay or a similar cell culture drug resistance assay. PMID- 7981055 TI - Inhibition of gastric cancer cell proliferation by antisense oligonucleotides targeting the messenger RNA encoding proliferating cell nuclear antigen. AB - Proliferating cell nuclear antigen (PCNA) is a nuclear protein that regulates DNA synthesis by DNA polymerase delta, and is essential for DNA replication. PCNA expression level is related to the malignancy of gastric cancer cells. Seven different gastric cancer cell lines and two kinds of control cell lines were treated with antisense oligonucleotides complementary to the messenger RNA of PCNA. Treatment of each gastric cancer cell line with antisense oligonucleotides at concentration of 10-40 microM inhibited the cell growth, colony formation and PCNA protein production in a dose-dependent manner, but only affected normal cells slightly. A random sequence oligomer showed no effect. These results show that PCNA is essential for gastric cancer cell proliferation and that the use of synthetic oligonucleotides is an effective way of producing antisense-mediated changes in the behaviour of human gastric cancers. PMID- 7981054 TI - Human stomach carcinoma-specific T cells derived from the tumour-draining lymph nodes. AB - In this paper we investigate the reactivity pattern of T cells from stomach carcinoma patients against autologous tumour cells. T cells obtained from the tumour environment, tumour-draining lymph nodes and peripheral blood were cloned in 78 patients with stomach cancer and anti-tumour cytotoxic T lymphocytes (CTLs) precursor frequencies were assessed in each sample by using limiting dilution analysis. When tumour-specific CTLs were tested for specific T-cell killing by using only low doses of Interleukin 2 (100 U ml-1), a moderate rate of proliferation frequency of T cells (0.047) and specific cytotoxicity (12%) were observed in lymph node populations. When both IL-2 and autologous tumour cells in mixed lymphocyte tumour cultures (MLTCs) were used for stimulation, a dramatic increase in number (0.1) and in specific lytic activity (46%) could be measured. No effect or specific activity to tumour cells was observed with peripheral blood lymphocytes and tumour-infiltrating lymphocytes. PMID- 7981056 TI - DNA-targeted 2-nitroimidazoles: in vitro and in vivo studies. AB - A series of compounds in which a 2-nitroimidazole is linked to a DNA intercalating phenanthridine moiety has been synthesised. Previously, three such compounds, termed nitroimidazole-linked phenanthridines or NLPs, were tested in vitro and showed a greatly enhanced molar efficiency as hypoxic cell radiosensitisers and cytotoxins compared with the untargeted 2-nitroimidazole, misonidazole. Since the cytoxicity of these compounds was shown to be inversely proportional to linker chain length while radiosensitising ability was dependent of it, compounds with five and six carbons in the chain were synthesised in an attempt to lower the toxicity of the drugs while increasing their ability to 'scan' DNA for target radicals. These compounds and a comparison series of n alkylated phenathridinium ions have been characterised and evaluated in vitro using Chinese hamster ovary and V79 cells and their effects compared with misonidazole. Based on in vitro results, one member of the series was selected and evaluated in vitro using a V79 spheroid tumour model and in vivo using an SCCVII transplantable tumour system. These studies have demonstrated the potential utility of this class of compound. PMID- 7981057 TI - Determinants of trimetrexate lethality in human colon cancer cells. AB - We examined the cytotoxicity and biochemical effects of the lipophilic antifol trimetrexate (TMQ) in two human colon carcinoma cell lines, SNU-C4 and NCI-H630, with different inherent sensitivity to TMQ. While a 24 h exposure to 0.1 microM TMQ inhibited cell growth by 50-60% in both cell lines, it did not reduce clonogenic survival. A 24 h exposure to 1 and 10 microM TMQ produced 42% and 50% lethality in C4 cells, but did not affect H630 cells. Dihydrofolate reductase (DHFR) and thymidylate synthase were quantitatively and qualitatively similar in both lines. During drug exposure, DHFR catalytic activity was inhibited by > or = 85% in both cell lines; in addition, the reduction in apparent free DHFR binding capacity (< or = 20% of control), depletion of dTTP, ATP and GTP pools and inhibition of [6-3H]deoxyuridine incorporation into DNA were similar in C4 and H630 cells. TMQ produced a more striking alteration of the pH step alkaline elution profile of newly synthesised DNA in C4 cells compared with 630 cells, however, indicating greater interference with DNA chain elongation or more extensive DNA damage. When TMQ was removed after a 24 h exposure to 0.1 microM, recovery of DHFR catalytic activity and apparent free DHFR binding sites was evident over the next 24-48 h in both cell lines. With 1 and 10 microM, however, persistent inhibition of DHFR was evident in C4 cells, whereas DHFR recovered in H630 cells. These data suggest that, although DHFR inhibition during TMQ exposure produced growth inhibition, DHFR catalytic activity 48 h after drug removal was a more accurate predictor of lethality in these two cell lines. Several factors appeared to influence the duration of DHFR inhibition after drug removal, including initial TMQ concentration, declining cytosolic TMQ levels after drug removal, the ability to acutely increase total DHFR content and the extent of TMQ mediated DNA damage. The greater sensitivity of C4 cells to TMQ-associated lethality may be attributed to the greater extent of TMQ-mediated DNA damage and more prolonged duration of DHFR inhibition after drug exposure. PMID- 7981058 TI - Analysis of adenomatous polyposis coli gene in thyroid tumours. AB - Familial adenomatous polyposis (FAP) is known to be associated with neoplasia of various tissues, including thyroid carcinoma. Germline mutations of the tumour suppressor gene APC, responsible for the predisposition to FAP, may therefore be involved in the pathogenesis of these tumours. In this report the structure of the APC gene has been investigated in 26 thyroid tumours, at different stages of dedifferentiation, that were surgically excised from patients with a negative history of FAP. Approximately 35% of the APC gene coding region, where most of the mutations are clustered, has been analysed by a combination of single-strand conformation polymorphism and direct sequencing. No significant alterations could be demonstrated in any sample examined. It is concluded that, at least in patients not affected by FAP, APC gene abnormalities do not seem to play a relevant role in the pathogenesis of thyroid carcinoma. PMID- 7981059 TI - Responses to paracrine chemotactic and autocrine chemokinetic factors and lung metastatic capability of mouse RAW117 large-cell lymphoma cells. AB - We studied the cell migration properties of poorly metastatic murine RAW117-P large-cell lymphoma cells, a highly lung metastatic subline (RAW117-L17) and a highly liver metastatic subline (RAW117-H10). L17 cells responded to the serum free conditioned medium (CM) of mouse lung microvessel endothelial cells (MLEs) and mouse lung fibroblasts (MLFs). The migration of L17 cells was also stimulated by its own CM and, to a lesser extent, by the CM of parental (P) and H10 cells. RAW117-P and -H10 cells responded poorly to all of the CM tested. Chequerboard analyses revealed that the migration-stimulating activities of MLE CM and MLF CM were mainly chemotactic, whereas those of L17, P and H10 CM were chemokinetic. We also analysed the effect of MLE CM and MLF CM in combination with L17, P or H10 CM on cell migration of the RAW117 sublines. The migration of lung metastatic subline L17 cells to MLE or MLF CM was enhanced when L17 CM was also present. This enhancement effect was not seen when P or H10 cells were exposed to MLE or MLF CM plus the CM from P or H10 cells respectively. Thus we found that the chemotactic response of lung metastatic large-cell lymphoma cells to paracrine migration stimulation factors from lung endothelial cells and fibroblasts in concert with an autocrine chemokinetic factor may be involved in RAW117 lung specific invasion and metastasis. PMID- 7981060 TI - Induction of the growth arrest and DNA damage-inducible gene GADD153 by cisplatin in vitro and in vivo. AB - The inability to assess the extent of tumour damage immediately following treatment is a major clinical obstacle to improving the management of cancer patients. Normally, the effectiveness of chemotherapy or radiation therapy cannot be determined for at least several weeks after treatment. We studied the increase in mRNA of the growth arrest and DNA damage-inducible gene GADD153 in human 2008 ovarian carcinoma cells in vitro and in vivo to determine whether treatment induced increases in the level of GADD153 mRNA could be used as a marker of the extent of tumour damage. GADD153 mRNA was increased in a transient, dose dependent manner by cisplatin (DDP) when the tumour cells were grown both in vitro and as tumour xenografts in nude mice. The magnitude of induction of GADD153 mRNA did not vary significantly between different 2008 xenografts treated with equal doses of DDP, and GADD153 mRNA induction correlated with the degree of in vitro cytotoxicity for two different schedules of drug exposure. DDP increased GADD153 mRNA levels in melanoma and head and neck xenograft models as well. We conclude that the increase in GADD153 mRNA can be used to detect tumour injury at time points as short as 24 h after administration of DDP. PMID- 7981061 TI - Photokilling of T-24 human bladder cancer cells with titanium dioxide. AB - A photoexcited titanium dioxide surface has a strong ability to decompose water into hydrogen and oxygen. We have studied this effect in order to use it to kill cancer cells in vitro and in vivo. A distinct cell killing effect was observed on cultured T-24 human bladder cancer cells treated with titanium dioxide particles and 300-400 nm UV light irradiation. Titanium dioxide plus UV light also dramatically suppressed the tumour growth of T-24 cells that were implanted in nude mice. Cells cultured on the titanium dioxide electrode were also killed under UV irradiation when the electrode was anodically polarised, suggesting that photogenerated holes are involved in the cell killing. The cell killing effect caused by titanium dioxide particles plus UV light irradiation was significantly hampered in the presence of L-cysteine and catalase, scavengers of hydroxyl radicals and hydrogen peroxide respectively. Transmission electron microscopic observations showed the titanium dioxide particles to be distributed on the cell surface and inside the cells. These results suggest that titanium dioxide particles under UV light irradiation produced photogenerated holes on the surface yielding hydroxyl radicals and hydrogen peroxide inside or outside the cells and the cells were then killed by the action of these highly oxidising molecules. The possible application of photoexcited titanium dioxide particles to cancer treatment as a new anti-cancer modality is discussed. PMID- 7981062 TI - Lack of a correlation between micronucleus formation and radiosensitivity in established and primary cultures of human tumours. AB - The radiation-induced genotoxic damage in three established cell lines and 15 primary cultures of human malignant melanoma and ovarian carcinoma showing different radiosensitivity was tested by the cytokinesis-block micronucleus assay. A dose-related increase in micronucleus frequency was observed in all the cell systems. The mean number of micronuclei per Gy of ionising radiation per binucleated cell was respectively 0.44 +/- 0.0075 and 0.43 +/- 0.04 for M14 and JR8 malignant melanoma cell lines and 0.19 +/- 0.013 for the A2780 ovarian cancer cell line. The number of micronuclei did not rank the cell lines in the same order of radiosensitivity as clonogenic cell survival, which showed a surviving fraction at 2 Gy of 0.38 +/- 0.02 for JR8, 0.34 +/- 0.05 for M14 and 0.22 +/- 0.007 for A2780. As regards primary tumour cultures, no correlation was observed between micronucleus induction and surviving fraction at 2 Gy. In conclusion, the discrepancy we observed between micronucleus formation and cell death raises doubts about the potential of the micronucleus assay as a preclinical means to predict radiosensitivity. PMID- 7981064 TI - The potential for enhanced tumour localisation by poly(ethylene glycol) modification of anti-CEA antibody. AB - Attachment of poly(ethylene glycol) (PEG) to proteins can greatly alter their pharmacological properties, including extending the plasma half-life and reducing immunogenicity, both of which are potentially beneficial to tumour targeting. IgG, F(ab')2 and Fab' fragments of the anti-CEA antibody A5B7 were chemically modified with PEG (M(r) 5,000), labelled with 125I and their pharmacokinetics compared with the unmodified forms in the LS174T colonic xenograft in nude mice. PEG modification of the intact antibody had little effect on biodistribution, although tumour localisation was slightly reduced. In contrast, similar modification of F(ab')2 and Fab'A5B7 significantly prolonged plasma half-life and increased radioantibody accumulation in the tumour and to a lesser extent in normal tissues, but reduced tissue to blood ratios. Prior to modification, Fab' A5B7 (M(r) 50,000) cleared more rapidly from the circulation than F(ab')2 (M(r) 100,000), but after PEG attachment their biodistributions converged, while the tumour to blood ratios were reduced and resembled that of the intact antibody. The enhanced tumour accumulation, reduced normal tissue to blood ratios and potentially reduced immunogenicity of fragments after PEG attachment may therefore prove superior to either unmodified fragments or intact antibody for antibody-targeted therapy, although the increased plasma half-life may necessitate the use of a clearance mechanism. PMID- 7981063 TI - Characterisation of a navelbine-resistant bladder carcinoma cell line cross resistant to taxoids. AB - A bladder carcinoma cell line (J82) was selected for resistance to the new vinca alkaloid navelbine. The resistance factor of the resistant subline (J82-NVB) to navelbine was 17. P-glycoprotein was not detected in the membrane of J82-NVB cells. The lack of cross-resistance to multidrug-resistant (MDR) drugs such as doxorubicin, epipodophyllotoxins and colchicine, the absence of increase in navelbine efflux and the fact that a reduced accumulation of the drug cannot account for the resistance level confirmed that the phenotype of resistance of J82-NVB cells is not a classical MDR phenotype. Moreover, verapamil did not reverse the resistance of J82-NVB cells. The cells were cross-resistant to vinca alkaloids and taxoids which share the same target protein: tubulin. Analysis of microtubules using immunofluorescence showed that disassembly of the microtubular network occurred for the same concentration of navelbine in sensitive and resistant cells. However, after treatment with a concentration of navelbine inducing depolymerisation in both sensitive and resistant cells, reassembly of the microtubular network was observed only in resistant cells. This study suggests that the mechanism of resistance of J82-NVB cells involves recovery from the inhibition of microtubule dynamics induced by drug treatment. PMID- 7981065 TI - Oxidation therapy: the use of a reactive oxygen species-generating enzyme system for tumour treatment. AB - Oxygen radicals induce cytotoxicity via a variety of mechanisms, including DNA damage, lipid peroxidation and protein oxidation. Here, we explore the use of a polyethylene glycol (PEG)-stabilised enzyme capable of producing reactive oxygen species (ROS), glucose oxidase (GO), for the purpose of harnessing the cytotoxic potential of ROS for treating solid tumours. PEG-GO (200 U), administered by two intratumoral injections 3 h apart, produced a significant growth delay in subcutaneous rat 9L gliomas as compared with control animals receiving heat denatured PEG-GO. Rats were protected from systemic toxicity by subsequent i.v. administration of PEG-superoxide dismutase (PEG-SOD) and PEG-catalase. In vivo tumour metabolic changes, monitored using 31P magnetic resonance spectroscopy (31P-MRS) 6 h following initial administration of PEG-GO, revealed a 96 +/- 2% reduction in the ATP/Pi ratio and a 0.72 +/- 0.10 unit decline in intracellular pH. A 3-fold sensitisation of 9L glioma cells in vitro to hydrogen peroxide could be achieved by a 24 h preincubation with buthionine sulphoximine (BSO). This study suggests that oxidation therapy, the use of an intratumoral ROS-generating enzyme system for the treatment of solid tumours, is a promising area which warrants further exploration. PMID- 7981066 TI - P-glycoprotein and glutathione S-transferase pi in childhood acute lymphoblastic leukaemia. AB - Blast cells obtained from 104 children with untreated acute lymphoblastic leukaemia were analysed for the expression of P-glycoprotein (P-170) and glutathione S-transfer pi (GST-pi) using immunohistochemistry. Expression of P 170 was detected in 36 of 104 patients (35%) and increased GST-pi was seen in 52 patients (50%). Coexpression of both resistance proteins was observed in 22 leukaemias (21%), whereas no evidence of the resistance markers was found in 38 cases (37%). In patients with P-170-positive leukaemic cells, a significantly lower probability of remaining in first continuous complete remission (CCR) was observed when compared with patients with P-170-negative tumours (P < 0.05). However, only a trend for a more frequent expression of P-170 was found in the leukaemic cells of patients who experienced relapses (P = 0.099). Overexpression of GST-pi was correlated with a higher relapse rate (P = 0.001) and a lower probability of remaining in first CCR (P = 0.01). Expression of P-170 and GST-pi was independent of sex, FAB type, immunological subtype and initial blast cell count. The multivariate analysis indicated that only the expression of P-170 is an unfavourable prognostic factor for children with acute lymphoblastic leukaemia in addition to the prognostic clinical factors. PMID- 7981067 TI - Selected micronutrient intake and the risk of colorectal cancer. AB - The relationship between estimated intake of selected micronutrients and the risk of colorectal cancer was analysed using data from a case-control study conducted in northern Italy. The study was based on 828 patients with colon cancer, 498 with rectal cancer and 2,024 controls in hospital for acute, non-neoplastic, non digestive tract diseases. Relative risks (RRs) of intake quintiles were computed after allowance for age, sex and other major potential confounding factors, including an estimate of total energy intake. No apparent trend in risk across intake quintiles was evident for retinol, vitamin D, methionine and calcium. For beta-carotene, ascorbic acid, vitamin E and folate there was a trend of a protective effect with increasing consumption: the RR for the highest versus the lowest quintile was 0.32 for beta-carotene, 0.40 for ascorbic acid, 0.60 for vitamin E and 0.52 for folate. These inverse associations were similar for colon and rectal cancer, and consistent across strata of sex and age. When simultaneous allowance was made for all these micronutrients, besides other covariates, the only persistent protective effects were for beta-carotene (RR = 0.38 for the highest quintile) and ascorbic acid (RR = 0.52). Whether this reflects a specific, or stronger, effect of these micronutrients, rather than problems of collinearity between micronutrients or other limitations of the data, remains open to discussion. Still, this study suggests that specific micronutrients may exert an independent protective effect against colorectal carcinogenesis. PMID- 7981068 TI - How safe is surveillance in patients with histologically low-risk non seminomatous testicular cancer in a geographically extended country with limited computerised tomographic resources? AB - In patients with clinical stage I non-seminomatous testicular cancer only limited information is available about the administrative problems with the surveillance programme, in particular if this policy is to be implemented in a geographically extended country with limited computerised tomography (CT) resources. One hundred and two patients with non-seminomatous testicular cancer clinical stage I and low risk histology (MRC criteria, UK) were followed by the surveillance policy for at least 1 year after orchiectomy (median 47 months, range 21-81 months). Twenty-two patients (22%) relapsed after a median time of 5 months (range 2-18 months), 14 of them in the retroperitoneal space. Serum alpha-fetoprotein and/or human chorionic gonadotrophin were elevated in eight of the 22 relapsing patients. The progression-free and cancer-corrected survival rates were 78% and 99% respectively. Patient non-compliance did not represent a major problem, whereas the regular and adequate performance of necessary CT examinations yielded some administrative difficulties. One and 3 years after orchiectomy about 50% of the relapse-free patients had no psychological problems and were satisfied with the surveillance programme, whereas 46% reported minor and 4% major psychological distress. Despite non-negligible administrative difficulties in geographically extended countries, surveillance is feasible and safe in compliant patients with low-risk non-seminomatous testicular cancer stage I. The responsible cancer centre and the local hospitals should establish a high degree of cooperation and enable adequate follow-up examinations in these patients. PMID- 7981069 TI - Comparison of granisetron alone and granisetron plus dexamethasone in the prophylaxis of cytotoxic-induced emesis. AB - Two hundred and seventy-eight adult chemonaive patients, receiving moderately emetogenic chemotherapy were randomly allocated to receive either intravenous (i.v.) granisetron 3 mg plus i.v. dexamethasone 8 mg or i.v. granisetron 3 mg plus i.v. placebo dexamethasone prior to chemotherapy. Eight-two per cent of all patients recruited were female, and 91% of all patients consumed less than 10 units of alcohol per week, suggesting a study population with an increased risk of nausea and vomiting. In the first 24 h 85% of patients who received granisetron plus dexamethasone were complete responders compared with 75.9% of the patients receiving granisetron alone (P = 0.053). There were statistically significant improvements in complete response over 7 days (P = 0.029) and in the numbers of patients receiving rescue antiemetic (P = 0.0004). Toxicity was minimal with no significant differences between treatment groups. These results confirm the antiemetic activity of granisetron and show that it has an additive effect in combination with dexamethasone. PMID- 7981070 TI - Changes in use of breast-conserving therapy in years 1978-2000. AB - The treatment of breast cancer patients has changed rapidly in the past decade, but empirical data at local and national level are scarce. Predicting the consequences of screening for primary treatment is consequently difficult. The aim of this analysis of records on admissions to hospital of women with breast cancer and/or for breast surgery (1975-90) together with a survey of all Dutch radiotherapy departments (1986-88) is to show the change in breast-conserving therapy and other primary treatment before the start of breast cancer screening in The Netherlands. There was a modest increase in breast-conserving therapy after 1981, coinciding with the first publication on its trial, followed by a sharp increase between 1985 and 1990, after the second publication. At the end of that 5 year period, 36% of all women with newly diagnosed invasive breast cancer underwent this type of surgery. Breast-conserving surgery is always followed by radiotherapy, but there has been a clear reduction in post-operative radiation after mastectomy. The percentage of breast-conserving therapy is at present higher in The Netherlands than in the USA. Implementing the Dutch screening programme will result in a maximum increase in breast-conserving therapy at national level of 34%, which stabilises at +21%, or a 50% maximum increase at local level. The number of women treated by mastectomy will ultimately decrease by 9%. Given the rapidity of change towards the use of breast-conserving surgery, which is enhanced by screening, recent information will be needed in predicting capacity and assessing whether screen-detected women are treated adequately. PMID- 7981071 TI - Methylprednisolone enhances the efficacy of ondansetron in acute and delayed cisplatin-induced emesis over at least three cycles. Ondansetron Study Group. AB - This double-blind multicentre study has been carried out in order to confirm the improvement of ondansetron's antiemetic efficacy when combined with a corticosteroid and to determine whether this increased efficacy is maintained over three chemotherapy courses. One hundred and two patients receiving their first course of cisplatin (50-120 mg m-2)-containing chemotherapy were randomised to receive one of the two following treatments: 8 mg OND i.v. injection and 120 mg MPD i.v. injection before chemotherapy, followed 8-12 h later by an 8 mg OND tablet and a 16 mg MPD tablet (oral treatment administered twice daily for 3-5 days): or 8 mg OND plus placebo i.v. injection before chemotherapy, followed by 8 12 h later by an 8 mg OND tablet and placebo p.o. (oral treatment administered twice daily for 3-5 days). The number of emetic episodes (EEs = vomits + retches) and the grade of nausea were recorded. Of the 101 patients studied (efficacy analysis), complete or major control (0-2 EEs) was experienced in 90.4% of patients in the first 24 h in the OND/MPD group compared with 71.4% of patients in the OND group during the first course. This difference in favour of OND/MPD was noted over the three courses and is statistically significant. In the control of delayed emesis (worst day between days 2 and 6) there is a trend in favour of the OND/MDP group during the first course [56.2% vs 43.2% for complete response (no emetic episodes)] which was statistically significant on courses 2 and 3. The global antiemetic control over the course was always in favour of OND/MPD, which leads to a better efficacy maintained over the three courses. Both treatments were well tolerated. The results of this study confirm the increased antimetic efficacy of ondansetron and methylprednisolone in combination in cisplatin induced acute and delayed emesis which led to a better maintained efficacy over three repeated chemotherapy courses. PMID- 7981072 TI - Linkage studies in a Li-Fraumeni family with increased expression of p53 protein but no germline mutation in p53. AB - We report a family with the Li-Fraumeni syndrome (LFS) in whom we have been unable to detect a mutation in the coding sequence of the p53 gene. Analysis of linkage to three polymorphic markers within p53 enabled direct involvement of p53 to be excluded. This is the first example of a LFS family in whom exclusion of p53 has been possible. Four affected members of the family with sarcoma or premenopausal breast cancer showed increased expression of p53 protein in their normal tissues as detected by immunohistochemistry. It therefore appears that the LFS phenotype has been conferred by an aberrant gene, showing a dominant pattern of inheritance, which may be acting to compromise normal p53 function rather than by a mutation in p53 itself. In order to try to determine the chromosomal location of this putative gene, we have carried out studies of linkage to candidate loci. By these means we have excluded involvement of Rb1 and BRCA1 on chromosomes 13q and 17q respectively. The MDM2 oncogene on chromosome 12q was considered to be the prime candidate as MDM2 is amplified in sarcomas and the MDM2 product binds to p53. Furthermore, p53 mutation and amplification of MDM2 have been shown to be mutually exclusive events in tumour development. Linkage analysis to two polymorphic markers within MDM2 yielded a three-point LOD score of -5.4 at a recombination fraction theta equal to zero. Therefore MDM2 could be excluded. It is possible that the gene which is responsible for cancer susceptibility in this family, possibly via interaction with p53, will be important in the histogenesis of breast cancer in general. We are now carrying out further studies to locate and identify this gene. PMID- 7981073 TI - Expression of interleukin 10 in human melanoma. AB - The expression of interleukin 10 (IL-10) mRNA in human malignant melanoma was investigated by reverse transcriptase polymerase chain reaction analysis. Selective expression of IL-10 mRNA in tissues of primary melanomas and melanoma metastases was found in comparison with normal skin. In addition, strong expression of IL-10 mRNA and of biologically active IL-10 was detected in 3 out of 13 melanoma cell lines. Normal melanocytes consistently expressed low levels of IL-10 mRNA but did not produce detectable IL-10 protein, nor did keratinocytes or fibroblasts. The production of biologically active IL-10 by melanoma cell lines suggests that IL-10 mRNA in melanoma lesions may derive at least in part from the tumour cells themselves. Tumour-infiltrating cells, however, could also be a source of IL-10 in melanoma tissues. The presence of IL-10 in melanoma lesions may contribute to the postulated 'paralysis' of an anti-melanoma immune response. PMID- 7981074 TI - Insulin and glucose status, tissue and plasma lipids in patients with tumours of the ovary or endometrium: possible dietary implications. AB - The relationship between tumour growth, insulin status, blood lipids and adipose linoleic acid (LA, reflecting long-term LA intake) was studied in 19 Jewish women suffering from early and advanced stages (ES and AS) of ovarian and endometrial tumours. Blood insulin in patients with ES tumours was four times higher than the control value in cancer-free subjects, but fell to normal levels at AS and after ES surgery (PES). Tumours and abdominal adipose tissue (AAT) had 4-6 and 1.4-1.7 times as much insulin as non-cancerous control organs. Serum total cholesterol (CHOL) and LDL-cholesterol were high at ES, dropped below normal at AS, but normalised at PES, while HDL-cholesterol increased after ES surgery. Linoleic acid in subcutaneous adipose tissue (SAT) was high in controls (26.4 + 1.5% of total fatty acids), but lower in cancer patients (20.5 + 3.7%, P < 0.05), while palmitic acid showed the opposite change. The results suggest mobilisation of glucose, cholesterol and linoleic acid for the supply of energy and structural lipids to rapidly multiplying tumour cells and possibly for prostaglandin synthesis. They also raise the question of whether the high linoleic acid intake by the Jewish population in Israel predisposes individuals to tumour development. PMID- 7981075 TI - Tumour-associated trypsin inhibitor (TATI): comparison with CA125 as a preoperative prognostic indicator in advanced ovarian cancer. AB - We have evaluated the prognostic value of tumour-associated trypsin inhibitor (TATI) in stage III or IV ovarian cancer. Tumour-associated trypsin inhibitor (TATI) and CA 125 were determined in serum samples from 66 patients taken before primary surgery. TATI was elevated (> 22 micrograms l-1) in 27 patients (41%). These had a 5 year cumulative survival of 8%, whereas survival was 45% in 39 patients with normal preoperative TATI values. By contrast, the preoperative CA 125 level did not predict survival. In multivariate analysis which included age, stage, histological grade and preoperative TATI and CA 125 levels, patients with elevated preoperative TATI levels had a 2.3-fold relative risk of death (95% confidence interval 1.23-4.20; P = 0.002) compared with patients with normal preoperative levels. This result was comparable with the predictive value of primary residual tumour size, since patients with residual tumour larger than 2 cm in diameter had a 5.2-fold relative risk of death (95% confidence interval 2.55-10.68) compared with patients with a smaller or no residual tumour. Thus, preoperative determination of serum TATI may have a place in the pretreatment evaluation of patients with advanced ovarian cancer. PMID- 7981077 TI - Prognostic relevance of pretreatment proliferative rapidity of marrow blast cells in childhood acute lymphoblastic leukaemia. AB - Cell proliferation rate is a well-established prognostic factor in cancer, but it has not been considered to identify the risk group of childhood acute lymphoblastic leukaemia (ALL) at presentation. We carried out a study to demonstrate the prognostic importance of the rapidity of cell proliferation in patients with ALL. To measure the rapidity of cell proliferation we used the parameter relative to the area of silver-stained nucleolar organiser regions (AgNORs) as evaluated by morphometric analysis on smeared marrow blast cells. The mean AgNOR area of leukaemic marrow cells was measured in 119 children. By using a cut-off value of 3 microns2, we identified a group of 91 children with low proliferating blast activity (mean AgNOR value 2.11 microns2) and a group of 28 children with high proliferating activity (mean AgNOR value 3.29 microns2). The group of patients with a mean AgNOR value > 3 microns2 was characterised by a higher number of deaths, more frequent relapse and shorter time interval to relapse than the group of patients with mean AgNOR value < 3 microns2 (P < 0.01). Multivariate analysis performed to include T-cell immunophenotype, FAB morphology, leucocyte count and presence of mediastinal mass showed that the mean AgNOR value was the only independent predictor of unfavourable event-free survival probability (P > 0.01). Our results indicate that the rapidity of marrow blast cell proliferation is an important prognostic parameter in childhood ALL and should be routinely introduced in the group risk definition. PMID- 7981076 TI - Alteration of p53 gene in ovarian carcinoma: clinicopathological correlation and prognostic significance. AB - Inactivation of the tumour-suppressor gene p53 has been demonstrated in a variety of human tumours. We extracted DNA from paraffin-embedded tissues of 67 ovarian carcinoma samples (54 primary tumours, seven metastases and six tumours obtained after chemotherapy), and analysed allelic losses and mutations of the p53 gene using single-strand conformation polymorphism (SSCP) analysis of DNA fragments amplified by a polymerase chain reaction (PCR). Allelic loss was observed in 24 of 32 informative cases. The mutation was detected in 14 of 54 primary ovarian carcinomas: eight serous cystadenocarcinomas (SCA), 42%), five endometrioid adenocarcinomas (EA, 42%) and one mucinous cystadenocarcinoma (14%). The incidence of the alteration was higher in SCA and EA than in other histological types, but the difference was not statistically significant. The incidence of p53 gene abnormalities in ovarian carcinomas tended to be increased in patients with disease advanced (over FIGO stage II). Mutations were found in exons 5 and 7 only and consisted mainly of single nucleotide substitutions [9 or 14 (64%) in exon 7; 4 of 14 (29%) in exon 5]. In 13 of 14 cases, p53 gene mutations occurred concomitantly with losses of the normal allele. The status of the p53 gene in metastases and the tumours obtained after chemotherapy was identical to that in the primary tumours. The presence of p53 gene mutation did not correlate with histological grade, response to primary therapy and survival. These findings suggest that mutational alterations of the p53 gene are involved in the development of a significant proportion of some ovarian carcinomas (SCAs or EAs), especially in advanced stages. However, they may not be a marker predicting the biological behaviour or the outcome of the disease. PMID- 7981078 TI - Treatment of multiple myeloma according to the extension of the disease: a prospective, randomised study comparing a less with a more aggressive cystostatic policy. Cooperative Group of Study and Treatment of Multiple Myeloma. AB - The purpose of the study was to ascertain whether the prognostic significance of staging in multiple myeloma (MM) is influenced by the aggressiveness of effective induction treatment and/or by continuing or discontinuing maintenance chemotherapy. Patients with untreated stage I MM (defined according to Durie and Salmon) were randomised between being followed without cytostatics until the disease progressed and receiving six courses of melphalan and prednisone (MP-P) just after diagnosis; stage II patients were uniformly treated with MPH-P and stage III patients were randomised between MPH-P and four courses of combination chemotherapy with Peptichemio, vincristine and prednisone (PTC-VCR-P). Within each stage, responsive patients were randomised between receiving additional therapy only until maximal tumour reduction was reached (plateau phase) and continuing induction therapy indefinitely until relapse. With resistant, progressive or relapsing disease, patients originally treated with MPH-P for induction received combination chemotherapy and vice versa. The overall first response rate was 43.8% (42.2% in 206 stage I, II and III patients treated with MPH-P and 48.0% in 75 stage III patients treated with combination chemotherapy, P = NS). Combination chemotherapy was more myelotoxic than MPH-P and, in particular, caused more non-haematological side-effects. Both the less and the more aggressive induction policies gave the same disease control. Progression of disease was statistically similar in stage I patients who were initially left untreated and in t hose who received MPH-P just after diagnosis; median duration of first response was similar in stage III patients receiving MPH-P and in those on combination chemotherapy. In all stages, discontinuing or continuing maintenance did not alter the median duration of first response. The overall second response rate was 28.5% (34.0% to MPH-P and 25.3% to combination chemotherapy, P = NS). Median survival was greater than 78 months in stage I, was 46.3 months in stage II and was 24.3 months in stage III patients, still independent of both induction and post-induction policies. In MM, the significance of staging for survival is independent of both the aggressiveness of induction and of continuing or discontinuing maintenance chemotherapy after the maximal tumor reduction has been achieved. Both MPH-P and and the association of PTC, VCR and P are effective in inducing first response and also second response in patients failing on the alternative regimen, but PTC-VCR-P causes more side effects. Thus, the overwhelming majority of patients with MM can safely be given MPH-P as first therapy, and this treatment may be delayed in early diseases. PMID- 7981079 TI - Measurement of S-phase fraction and ploidy in sequential fine-needle aspirates from primary human breast tumours treated with tamoxifen. AB - Sequential fine-needle aspirates (FNAs) for cytodiagnosis and flow cytometry were taken from 21 patients with primary breast carcinoma at intervals ranging from 1 to 3 months after the commencement of first-line tamoxifen therapy. Nine patients achieved a sustained complete or near complete response over a 3-9 month period. The tumour cells from seven out of nine of these patients were initially aneuploid, while the remaining two patients had diploid tumours. An analysis of sequential FNAs showed that, in three out of the seven aneuploid tumours, only benign epithelial cells could be detected by cytology in the post-tamoxifen sample. In the remaining six cases, including the two diploid tumours, there was no change in ploidy but a reduction in S-phase fraction (SPF) to approximately 50% of the pretreatment level. In all cases, these changes in ploidy or SPF were seen with a mean lead time of 4 months before the tumour had reached clinical complete remission. None of these patients have relapsed after a mean follow-up period of 18 months. The tumours of 12 patients achieved no more than a temporary partial response to primary tamoxifen therapy. In seven out of eight of these cases, which were all initially aneuploid, sequential FNAs during tamoxifen therapy revealed either an increase or no change in the SPF with the tumour remaining aneuploid. In the remaining four cases the tumours were all recorded as being diploid in the pretreatment sample. However, although three of these cases had a temporary partial response to tamoxifen, an aneuploid component was picked up in repeat sequential FNAs with a mean lead time of 5 months before clinical confirmation of eventual disease progression. We conclude that changes in ploidy and SPF detected by flow cytometry may predict initial response and the likelihood of relapse of breast tumours to tamoxifen before clinical changes become evident. These data justify a larger study. PMID- 7981080 TI - Relationship of PS2 with response to tamoxifen therapy in patients with recurrent breast cancer. AB - PS2, an oestrogen-inducible protein, was measured in the cytosol of 230 primary tumours from patients who were subjected to first-line tamoxifen therapy for advanced disease without prior adjuvant therapy with tamoxifen. PS2 correlated positively with oestrogen receptor (ER, P < 0.01) and progesterone receptor content (PgR, P < 0.001), and with the length of progression-free survival (PFS, P = 0.05). Although not statistically significant, higher levels of PS2 (> or = 10 ng mg-1 protein) were also associated with increased probability of response to tamoxifen treatment and a longer total post-relapse survival (PRS). ER, PgR, menopausal status, site of disease and prior adjuvant chemotherapy were all associated with response to tamoxifen therapy and with PFS. In multivariate analysis for PFS, low levels of ER and PgR, visceral metastasis, a disease-free interval of less than 1 year and prior adjuvant chemotherapy were all significantly associated with an increased probability of a rapid disease progression after start of tamoxifen therapy. In the subset of 83 tumours with intermediate levels of ER and PgR (both > or = 10, but not both > or = 75 fmol mg 1 protein), PS2 was positively related with the length of PFS (P < 0.01) and PRS (P < 0.05). PS2 remained the strongest factor in multivariate analysis for PFS (P < 0.01) in this ER/PgR intermediate subgroup, but was not of predictive value in univariate or multivariate analysis for both PFS and PRS in tumours classified as ER/PgR low or high (> or = 75 fmol mg-1 protein). It is concluded that PS2 status may be used as a parameter, additional to ER and PgR, for better refinement of prediction of response to tamoxifen treatment in advanced breast cancer patients especially with intermediate ER/PgR levels in their primary tumour. PMID- 7981081 TI - NM23 expression in metastasis of malignant melanoma is a predictive prognostic parameter correlated with survival. AB - The management of patients presenting with metastatic malignant melanoma (MM) is hampered by the substantial variability in survival of these patients and the lack of prognostic markers. In the search for a reliable predictive parameter, we have investigated the expression of the nm23 gene, considered to be a major regulator of the metastatic process. We have analysed by Northern blot the nm23 mRNA level in tumour tissue obtained from metastases of 20 stage II and ten stage III patients with MM. Normal human tissues and benign naevi were simultaneously examined. The level of nm23 expression was highly heterogeneous in MM metastases, with a mean value which was higher than the mean level in normal tissues and naevi. Correlative study was focused on the overall survival following resection of the metastasis in which nm23 Northern blot analysis was performed. Patients displaying higher nm23 expression in metastatic tissue (above the mean level) tended to have a longer survival than others (P = 0.08), and this difference was significant for patients presenting with isolated regional lymph node involvement (P = 0.035). The time from biopsy of the primary MM to the appearance of the first lymph node metastasis also showed a positive correlation with the nm23 mRNA level in this metastasis. The present study is not only in accordance with previous reports showing that the nm23 gene may be implicated in MM progression, but also suggests the reliable value of nm23 expression as a prognostic marker for patients presenting with metastatic MM. PMID- 7981082 TI - The impact on colorectal cancer survival of cases registered by 'death certificate only': implications for national survival rates. AB - This paper describes the effect of including death certificate only (DCO) registrations on 5 year relative survival rates for colorectal cancer in four district health authorities (DHAs) in south-east England. A retrospective case note study was set up to examine all cases of colorectal cancer listed in the Thames Cancer Registry (TCR) as having been diagnosed in 1983 and 1988 and resident in one of four districts, A, B, C and D. A total of 673 sets of cases notes were requested from all hospitals within the four districts, including 150 sets on DCO cases. Of 465 (69%) sets of case notes retrieved, 378 (72.3%) were non-DCO cases. Of these, 14 were excluded from survival analysis because of missing dates of diagnosis or death in the notes. Eighty-seven (58.0%) sets of case notes were retrieved on DCO registrations, of which seven were excluded because no date of diagnosis was available in the notes. Retrieval rates on case note registrations varied by DHA of residence: 73.3% in DHA A, 96.6% in DHA B, 34.5% in DHA C and 79.2% in DHA D. The corresponding figures for DCO registrations were 63.5%, 69.0%, 7.4% and 76.2%. Cumulative relative 5 year survival rates by DHA of residence were calculated first for cases registered from case notes and then for all cases including those registered solely from a death certificate. The total number of cases used in the survival analysis was 444 (18% DCOs). In all four DHAs, 5 year survival decreased with the inclusion of DCO registrations: by 9.1% in district A (from 52.8 to 43.7), by 4.5% in district B (from 59.6 to 55.1), by 4.8% in district C (from 80.0 to 75.2) and by 7.6% in district D (from 31.4 to 23.8). The overall reduction in survival was 8.6%. The exclusion of death certificate only registrations from survival data is an important source of bias. Using TCR data, we compared DCO proportions for colorectal cancer with other sites. DCO proportions were shown to vary by tumour site and survival time. The DCO registration is an important quality measure of ascertainment and follow-up. OPCS should publish DCO proportions by registry area and cancer site. Registries should implement DCO monitoring as part of quality improvement programmes. PMID- 7981083 TI - Cancer mortality and morbidity among workers at the Sellafield plant of British Nuclear Fuels. AB - The mortality of all 14,282 workers employed at the Sellafield plant of British Nuclear Fuels between 1947 and 1975 was studied up to the end of 1988 and cancer incidence was examined from 1971 to 1986. This updates a previous report on mortality only up to the end of 1983. Ninety-nine per cent of the workers were traced satisfactorily. Cancer mortality was 4% less than that of England and Wales [standardised mortality ratio (SMR) = 96; 95% confidence interval (CI) = 90,103] and the same as that of Cumbria (SMR = 100: Cl = 94,107). Cancer incidence was 10% less than that of England and Wales [standardised registration ratio (SRR) = 90; Cl = 83.97] and 18% less than that of Northern Region (SRR = 82; Cl = 75.88). Cancer mortality rates were significantly in excess of national rates for cancers of the pleura (nine observed, 2.6 expected; P = 0.001), thyroid (six observed, 1.8 expected; P = 0.01) and ill defined and secondary sites (53 observed, 39.2 expected; P = 0.02). There were significant deficits of cancers of the liver and gall bladder, larynx and lung. Among radiation workers there were significant positive correlations between accumulated radiation dose and mortality from cancers of ill-defined and secondary sites (10 year lag: P = 0.01) and for leukaemia (2 year lag: P = 0.009), but not for cancers of the pleura and thyroid cancer. Previous findings of such associations with multiple myeloma and bladder cancer were less strong. There was a significant excess of incident cases of cancer of the oesophagus (P = 0.01), but this was not associated with accumulated radiation dose. For cancers other than leukaemia, the dose-response risk estimates were below those of the adult atomic bomb survivors, but the 90% confidence interval included risks of zero and of 2-3 times higher. For leukaemia (12 deaths, excluding CLL), under an excess relative risk model, the risk estimate derived for the Sellafield workers was about four times higher than that for the adult atomic bomb survivors with a confidence interval ranging from a half to nearly 20 times that of the atomic bomb survivors. Overall, however, there was no excess of leukaemia among the workers compared with national rates. PMID- 7981085 TI - S-phase fraction and survival benefit from adjuvant chemotherapy or radiotherapy of breast cancer. AB - Cancer chemotherapy interacts with cell proliferation, but data on the relationship between cancer cell replication and the effect of adjuvant chemotherapy are scarce. We have investigated the S-phase fractions of the primary tumour from premenopausal breast cancer patients who participated in a randomised trial comparing 12 cycles of polychemotherapy (CMF) with post operative radiotherapy. DNA flow cytometry was performed on frozen tissues from 208 primary breast carcinomas, of which the S-phase fraction was estimated in 176 cases. There was a significantly higher benefit from CMF among patients with a high S-phase fraction (P = 0.0033). The relative risk of distant recurrence or death in the chemotherapy group as compared with the radiotherapy group was 0.19 for patients whose tumours had an S-phase fraction of 10% or over (95% CI 0.07 0.51) and 1.55 (0.88-2.73) for patients whose tumours showed lower S-phase levels. The interaction was still significant in multivariate analysis (P = 0.0057), including lymph node metastases, tumour size and oestrogen receptor content. We conclude that the benefit from adjuvant chemotherapy compared with radiotherapy is largely confined to patients with highly proliferative tumours. PMID- 7981084 TI - Intracavitary prophylactic treatment with interferon alpha 2b of patients with superficial bladder cancer is associated with a systemic T-cell activation. AB - The activation and proliferation of peripheral blood mononuclear cells (PBMNCs) are complex processes involving several surface molecules, cell secretion and response to cytokines. This paper investigates the immunomodulatory effect of prophylactic treatment with interferon alpha 2b (IFN-alpha 2b) upon the blastogenic response of PBMNCs from patients with superficial transitional cell carcinoma (STCC) of the bladder to mitogenic signals that interact with surface molecules [phytohaemagglutinin, PHA and anti-CD3 monoclonal antibodies, (MAbs)]. PBMNCs from the patients were studied prior to the transurethral resection (TUR) of the tumour, during the second month of prophylactic intravesical instillation of IFN-alpha 2b and 3 and 6 months after finishing the instillation treatment. The [3H]thymidine uptake of PBMNCs from 17 patients with STCC of the bladder after 5 days of PHA and anti-CD3 MAb stimulus was found to be significantly lower than that of healthy controls (P < 0.05). The addition of interleukin 2 (IL-2) to the culture medium did not correct this defective proliferative response to PHA and the anti-CD3 MAb. There were no significant differences between IL-2 production in PBMNCs from STCC patients after stimulation with PHA and in PBMNCs from healthy controls (P > 0.05). Patients without evidence of recurrence showed a significantly enhanced proliferative response in PBMNC to PHA and anti-CD3 MAb after intravesical prophylactic treatment with interferon-alpha 2b in the follow up examinations 3 and 6 months after treatment (P < 0.01). However, three patients had evidence of tumour recurrence, and they showed no enhancement of the PBMNC proliferative response to these mitogens in the same examinations. In conclusion, the prophylactic intracavitary treatment of STCC with IFN-alpha 2b may induce a systemic immunomodulatory effect which is associated to the clinical evolution of the disease. PMID- 7981086 TI - Peroperative radioimmunodetection of ovarian carcinoma using a hand-held gamma detection probe. AB - Radioimmunoscintigraphy (RIS) can be used in the preoperative localisation of ovarian carcinoma to demonstrate uptake of radiolabelled monoclonal antibodies into neoplastic tissue. The tissue uptake of radiotracer was evaluated at laparotomy in 16 patients with suspected ovarian cancer who had preoperative RIS using technetium-99m-labelled monoclonal antibodies SM3 and H17E2. A gamma detection probe (gamma DP) was used to measure uptake in possible tumour deposits at operation and also the uptake in tissues resected for histology. The percentage uptake of the initial injected dose of radiotracer was also measured in resected tissues. Activity was found to be significantly higher in malignant than in non-neoplastic tissue by all three methods of evaluation. The gamma DP used peroperatively yielded a 82% sensitivity with a 72% specificity for an uptake ratio of 1.5:1. When tissue was examined immediately after resection, for a 100% specificity the sensitivity was 64%. In vitro measurements of monoclonal antibody uptake by tissue similarly gave a 65% sensitivity with a 100% specificity. Peroperative and immediate post-operative measurements of tissue radioactivity can be performed quickly and conveniently, and in some cases may be of benefit in the localisation of tumour at laparotomy and in providing extra information when tissue is examined by frozen section. PMID- 7981087 TI - Expression and mutational analysis of Nm23-H1 in liver metastases of colorectal cancer. AB - It has been proposed that nm23-H1, a candidate suppressor gene for metastasis, plays an important role in metastasis formation of human tumours. In order to investigate its role in the progression of colorectal cancer, we analysed 22 liver metastases of this malignancy with respect to mutational changes, loss of heterozygosity and expression levels of nm23-H1. Although genetic alterations in nm23-H1 have recently been described in those colorectal adenocarcinomas which give rise to distant metastases, we were unable to detect any mutation in the coding sequence of nm23-H1 in the metastatic tissue itself. We further analysed the metastases with respect to allelic deletions at the chromosomal locus of nm23. However, no loss of heterozygosity could be detected in ten informative cases. Moreover, the mRNA expression levels of nm23-H1 in the metastatic tissues were not significantly different from those in normal colon mucosa. Thus, although nm23-H1 might be involved in metastasis suppression of certain tumour types, in colorectal tumour progression its role remains to be determined. PMID- 7981088 TI - Expression of sialyl-Tn predicts the effect of adjuvant chemotherapy in node positive breast cancer. AB - Sialyl-Tn (STn) is a carcinoma-associated carbohydrate determinant expressed on cancer-associated mucins and has the structure NANA alpha(2-6)alpha GalNAc. Expression of STn in colon and ovarian cancer is associated with a poor prognosis independent of tumour grade, stage or histological type. We have examined 237 cases of primary breast cancer for expression of this antigen using the antibody HB-STn (Dako). The frequency of STn expression was 31% in the whole group, 36% in the node-negative and 28% in the node-positive group. Survival was lower, but not significantly so, in the STn-positive group (P = 0.07), but this effect was highly significant for patients with node-positive disease (P < 0.002), the curves for node-negative disease being coincident (P = 0.31). In node-positive disease the effect was limited to those receiving adjuvant chemotherapy (P = 0.001). In a multivariate (Cox) analysis on the whole group STn staining, combined with adjuvant chemotherapy, showed a highly significant correlation with survival. In STn-negative cases, adjuvant chemotherapy improved survival (relative risk 2.3, 95% confidence intervals 1.4-3.9), whereas adjuvant chemotherapy did not influence survival in patients which expressed STn (relative risk 1.1, 95% confidence intervals 0.6-2.2). Thus, by either direct or indirect mechanisms, STn positivity appears to be a marker of resistance to adjuvant chemotherapy. PMID- 7981089 TI - Surveillance or etoposide-containing combination chemotherapy for stage I non seminomatous germ cell tumours of the testis (NSGCTT) PMID- 7981090 TI - Transforming growth factor beta isoforms in breast cancer. PMID- 7981091 TI - Descriptions of Prevotella tannerae sp. nov. and Prevotella enoeca sp. nov. from the human gingival crevice and emendation of the description of Prevotella zoogleoformans. AB - Prevotella tannerae sp. nov. and Prevotella enoeca sp. nov. from the human gingival crevice are described. These organisms are obligately anaerobic, non spore-forming, nonmotile, gram-negative, rod-shaped bacteria that ferment carbohydrates and produce succinic and acetic acids. Bile inhibits growth. Some strains (38%) of P. tannerae produce colonies with a tan to black pigment when they are grown on rabbit blood agar. The type strains are P. tannerae ATCC 51259 and P. enoeca ATCC 51261. In addition, the description of Prevotella zoogleoformans is emended to exclude strains now recognized as members of Prevotella heparinolytica. PMID- 7981092 TI - Isolation and characterization of Desulfitobacterium dehalogenans gen. nov., sp. nov., an anaerobic bacterium which reductively dechlorinates chlorophenolic compounds. AB - An organism that is able to reductively ortho-dechlorinate 2,4-dichlorophenol and 3-chloro-4-hydroxyphenylacetate (3-Cl-4-OHPA) was isolated from a methanogenic lake sediment. This organism, an anaerobic, motile, Gram-type-positive, rod shaped bacterium, grew in the presence of 0.1% yeast extract when pyruvate, lactate, formate, or hydrogen was used as the electron donor for reductive dehalogenation of 3-Cl-4-OHPA. Sulfite, thiosulfate, and sulfur were reduced to sulfide, nitrate was reduced to nitrite, and fumarate was reduced to succinate. Dissimilatory reduction of sulfate could not be demonstrated, and no adenylylsulfate reductase was detected with an immunoassay. The organism fermented two pyruvate molecules to one lactate molecule, one acetate molecule, and one carbon dioxide molecule. The pH and temperature optima for both growth and dechlorination of 3-Cl-4-OHPA were 7.5 and 38 degrees C, respectively. The doubling time under these conditions was approximately 3.5 h. On the basis of the results of a 16S rRNA analysis and the inability of the organism to use sulfate as an electron acceptor, strain JW/IU-DC1 is described as the type strain of the new taxon Desulfitobacterium dehalogenans gen. nov., sp. nov. PMID- 7981094 TI - Porphyromonas gingivicanis sp. nov. and Porphyromonas crevioricanis sp. nov., isolated from beagles. AB - Two new species, Porphyromonas gingivicanis and Porphyromonas crevioricanis, are proposed for black-pigmented, asaccharolytic, anaerobic, nonmotile, non-spore forming, gram-negative, rod-shaped organisms. These organisms were isolated from the gingival crevicular fluids of beagles. P. gingivicanis and P. crevioricanis do not grow in the presence of 20% bile. They exhibit less than 5% DNA-DNA homology with the type strains of Porphyromonas gingivalis (strain ATCC 33277), Porphyromonas endodontalis (strain ATCC 35406), and Porphyromonas asaccharolytica (strain ATCC 25260), which were isolated from humans, or with the type strains of Porphyromonas salivosa (strain NCTC 11632) and Porphyromonas circumdentaria (strain NCTC 12469), which were isolated from cats. The major cellular fatty acid of P. gingivicanis and P. crevioricanis is 13-methyltetradecanoic acid (iso-C15:0 acid). Glutamate and malate dehydrogenases are present in both species, and 6 phosphogluconate and glucose-6-phosphate dehydrogenases are absent; neither organism exhibits trypsin activity. P. gingivicanis and P. crevioricanis produce large amounts of acetic and isovaleric acids and minor amounts of isobutyric and succinic acids as end products of metabolism in GAM medium. P. gingivicanis also produces large amounts of butyric acid and small amounts of propionic acid, while P. crevioricanis produces large amounts of propionic acid and minor amounts of butyric and phenylacetic acids. The G+C contents of the DNA of P. gingivicanis is 41 to 42 mol%; the G+C content of the DNA of P. crevioricanis is 44 to 45 mol%. Catalase is produced by P. gingivicanis but not by P. crevioricanis; strains of P. crevioricanis agglutinate sheep erythrocytes, but strains of P. gingivicanis do not.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7981093 TI - Phylogenetic position of the genus Hydrogenobacter. AB - The genus Hydrogenobacter consists of extremely thermophilic, obligately chemolithotrophic organisms that exhibit anaerobic anabolism but aerobic catabolism. Preliminary studies of the phylogenetic position of these organisms based on limited 16S ribosomal DNA sequence data suggested that they belong to one of the earliest branching orders of the Bacteria. In this study, the complete 16S ribosomal DNA sequences of two type strains, Hydrogenobacter thermophilus TK 6 and Calderobacterium hydrogenophilum Z-829, and another isolate, Hydrogenobacter sp. strain T3, were determined, and the phylogenetic positions of these organisms were examined. Our results revealed that the two type strains are members of a single genus, the genus Hydrogenobacter. Our results also verified the previous conclusion that the Aquifex-Hydrogenobacter complex belongs to a very early branching order, the "Aquificales." Within this order, the relationships among the various organisms are such that only a single family, the "Aquificaceae," can be recognized at this time. Given the early branching point of the "Aquificales," the characteristics of these organisms support the view that the last common ancestor of existing life was thermophilic and suggest that this ancestor may have fixed carbon chemoautotrophically. PMID- 7981095 TI - Candida caseinolytica sp. nov., a new species of yeast occurring in necrotic tissue of Opuntia and Stenocereus species in the southwestern United States and Baja California, Mexico. AB - We describe Candida caseinolytica, a new yeast species which occurs in rotting tissues of opuntias and other cacti in the North American Sonoran Desert and a few other localities. This small-celled, slowly growing yeast does not ferment any sugar and assimilates a limited number of carbon compounds, including 2- and 5-ketogluconic acids. It exhibits strong extracellular proteolytic activity on casein at pH 6.5, but gelatin is not hydrolyzed or is only weakly hydrolyzed by a few strains. The type strain of C. caseinolytica is strain UCD-FST 83-438.3 (= ATCC 90546 = CBS 7781). PMID- 7981096 TI - Streptococcus phocae sp. nov., a new species isolated from clinical specimens from seals. AB - A new beta-hemolytic streptococcal species, Streptococcus phocae, was isolated from organ specimens obtained from seals. This taxon is described on the basis of the results of a study of 22 strains. S. phocae was serologically somewhat heterogeneous (group antigen -/F/C). Strains belonging to this species exhibited high levels of DNA-DNA homology to each other, as determined by DNA-DNA hybridization, but low levels of DNA-DNA homology to the type strains of other streptococcal species. A simple scheme for the differentiation of S. phocae from other beta-hemolytic streptococci is presented. Strain 8399 H1 (= NCTC 12719) is the type strain of S. phocae. PMID- 7981097 TI - Phylogenetic analysis of members of the genus Porphyromonas and description of Porphyromonas cangingivalis sp. nov. and Porphyromonas cansulci sp. nov. AB - The partial 16S rRNA gene sequences of representative strains of two groups of anaerobic, gram-negative, pigmented, asaccharolytic, rod-shaped bacteria isolated from subgingival plaque of dogs with naturally occurring periodontal disease were determined. A comparative analysis of the rRNA sequence data revealed that the two groups of organisms represent previously unknown lines of descent within the genus Porphyromonas. On the basis of our phylogenetic findings and the phenotypic distinctiveness of the organisms, two new species, Porphyromonas cangingivalis and Porphyromonas cansulci, are proposed. PMID- 7981098 TI - Acholeplasma brassicae sp. nov. and Acholeplasma palmae sp. nov., two non-sterol requiring mollicutes from plant surfaces. AB - Two mollicutes (strains 0502T [T = type strain] and J233T), which were isolated from the surfaces of broccoli (Brassica oleracea var. italica) plants or the crown tissues of the coconut palm (Cocos nucifera), were capable of sustained growth in serum-free (or cholesterol-free) mycoplasma broth media. Examination by electron and dark-field microscopic techniques revealed that the cells of each strain were small, nonhelical, nonmotile, pleomorphic, and coccoid and that each cell was surrounded by a single cytoplasmic membrane. No evidence of a cell wall was found. The organisms were filterable and grew rapidly in most conventional mycoplasma culture medium formulations containing horse or fetal bovine sera under either aerobic or anaerobic conditions. The optimum temperature for growth of both organisms was 30 degrees C, but multiplication occurred over a temperature range from 18 to 37 degrees C. Both strains catabolized glucose, but did not hydrolyze arbutin, arginine, or urea. The genome size of strain 0502T was 1,215 kbp, and the DNA base composition (guanine-plus-cytosine content) was 35.5 mol%. The genome size of strain J233T was 1,610 kbp, and the DNA base composition was 30.0 mol%. The two isolates were not serologically related to each other or to the type strains of 11 previously described Acholeplasma species. Strain 0502 (= ATCC 49388) is the type strain of Acholeplasma brassicae sp. nov., and strain J233 (= ATCC 49389) is the type strain of Acholeplasma palmae sp. nov. PMID- 7981099 TI - Molecular characterization and application of random amplified polymorphic DNA analysis of Mrakia and Sterigmatomyces species. AB - The qualitative and quantitative monosaccharide spectra of purified yeast cell walls revealed that there are three phylogenetically distinct lineages of sterigma-forming basidiomycetous yeasts: (i) Kurtzmanomyces and Sterigmatomyces species, which contain high levels of mannose; (ii) Tilletiopsis species, which contain glucose, galactose, and small amounts of mannose; and (iii) Fellomyces, Kockovaella, Sterigmatosporidium, and Tsuchiyaea species, which appear to be closely related on the basis of their high levels of glucose and the presence of xylose. The yeast cell wall neutral sugars of Sporobolomyces antarcticus and Sterigmatomyces aphidis were similar to those of members of the genus Tilletiopsis. However, the possibility that these taxa are conspecific was eliminated by the results of a random amplified polymorphic DNA (RAPD) analysis. The conspecificity of Mrakia frigida and Mrakia nivalis, the conspecificity of Mrakia gelida and Mrakia stokesii, and the conspecificity of Sterigmatomyces halophilus and Sterigmatomyces indicus were confirmed by RAPD analysis results. RAPD analysis was found to be a simple and highly sensitive method which can be used to differentiate species at the DNA level; it can replace nuclear DNA nuclear DNA hybridization experiments for species identification, characterization, and delimitation. PMID- 7981100 TI - Chemical and molecular classification of Saccharomonospora strains. AB - The results of our experiments showed that the 5'-terminal sequences of 23S rRNAs can be used to distinguish different genera of actinomycetes, including the genera Streptomyces, Micromonospora, Amycolatopsis, and Saccharomonospora. There are small differences (< 1%) among the sequences of some strains belonging to the genera Streptomyces (two strains) and Saccharomonospora (seven strains). On the basis of the results of morphological and biochemical analyses, strain 9022 belongs in the genus Saccharomonospora; however, there are distinct differences in the cell wall compositions and the 5' termini of the 23S rRNA sequences of this strain and members of the genus Saccharomonospora. Hence, strain 9022 cannot be classified in the genus Saccharomonospora. PMID- 7981101 TI - Rapid characterization of four species of the Saccharomyces sensu stricto complex according to mitochondrial DNA patterns. AB - Several strains of the four sibling species of the genus Saccharomyces (S. bayanus, S. cerevisiae, S. paradoxus, and S. pastorianus) were characterized by using a rapid and simple method of restriction analysis of mitochondrial DNA. Patterns obtained with four-cutter endonucleases (such as AluI, DdeI, HinfI, and RsaI) made it possible to differentiate each species. S. cerevisiae and S. paradoxus presented a greater number of large fragments than S. pastorianus and S. bayanus with all the assay enzymes. With AluI and DdeI, species-specific bands clearly permitted differentiation between S. pastorianus and S. bayanus. To test the resolution of this method, wild Saccharomyces strains were analyzed. The correct assignment of these strains to a known taxon by this rapid method was confirmed by means of electrophoretic karyotyping. PMID- 7981102 TI - Diversity of Borrelia burgdorferi sensu lato evidenced by restriction fragment length polymorphism of rrf (5S)-rrl (23S) intergenic spacer amplicons. AB - The organization of the ribosomal genes is unique in Borrelia burgdorferi in that the rrl (23S) and rrf (5S) genes are tandemly duplicated. We took advantage of this uniqueness to assess the restriction polymorphism of PCR products obtained with primers at the 3' end of the first rrf gene and at the 5' end of the second rrl gene. An amplicon that was 226 to 266 bp long was generated from 99 to 100 B. burgdorferi sensu lato strains. The nuclease MseI restriction polymorphism of the amplicons provided a useful tool for identifying B. burgdorferi sensu stricto, Borrelia garinii, Borrelia afzelii (formerly group VS461), and Borrelia japonica (formerly group F63B). Furthermore, it allowed us to recognize four new genomic groups, which were confirmed by DNA-DNA hybridization data. Two of these genomic groups comprised European strains, and the other two groups contained American strains. The American genomic groups involved vectors with enzootic cycles quite different from those of B. burgdorferi sensu stricto, which previously was the only Lyme disease Borrelia species known to occur in the United States. Our method could be used for rapid screening of strain collections and for epidemiological and medical purposes. PMID- 7981103 TI - Transfer of Rhodococcus aichiensis Tsukamura 1982 and Nocardia amarae Lechevalier and Lechevalier 1974 to the genus Gordona as Gordona aichiensis comb. nov. and Gordona amarae comb. nov. AB - We investigated the taxonomic status of Rhodococcus aichiensis DSM 43978T (T = type strain) and Nocardia amarae DSM 43392T by using both chemotaxonomic and genetic methods. The occurrence of MK-9(H2) as the predominant menaquinone, the presence of relatively long-chain mycolic acids (48 to 62 carbon atoms), and the phylogenetic position as determined by a 16S ribosomal DNA sequence analysis provide strong evidence that both R. aichiensis and N. amarae should be transferred to the genus Gordona as Gordona aichiensis and Gordona amarae, respectively. PMID- 7981104 TI - Phylogeny of the yeast genera Hanseniaspora (anamorph Kloeckera), Dekkera (anamorph Brettanomyces), and Eeniella as inferred from partial 26S ribosomal DNA nucleotide sequences. AB - Partial 26S ribosomal DNA sequences of species assigned to the genera Hanseniaspora, Kloeckera, Dekkera, Brettanomyces, and Eeniella were determined. A phylogenetic analysis of the sequences showed that the genus Eeniella is derived within the genus Brettanomyces and that the genus Hanseniaspora (anamorph Kloeckera) is not closely related to the genus Dekkera (anamorph Brettanomyces). As a consequence, the name Eeniella is reduced to synonymy with the name Brettanomyces. In addition, our data do not support reassignment of certain Hanseniaspora species to the recently revived genus Kloeckeraspora. PMID- 7981105 TI - Electrophoretic karyotypes of authentic strains of the sensu stricto group of the genus Saccharomyces. AB - A comparative electrophoretic karyotyping study was performed with several certified authentic strains of the four species that could be distinguished by nuclear DNA (nDNA)-nDNA reassociation data within the sensu stricto group of the genus Saccharomyces. A multivariate analysis of the polymorphisms observed in pulsed-field gel electrophoretic profiles (numbers and molecular weights of separated units) revealed that the strains could be separated into four clusters that corresponded to the taxa that were distinguished on the basis of nDNA comparisons. Discrepancies between nDNA reassociation data and membership in the corresponding clusters were observed only with two strains of Saccharomyces paradoxus. Blind tests carried out with additional industrial strains confirmed the general validity of the statistical model created for comparison of karyotypes within the species included in Saccharomyces sensu stricto. PMID- 7981106 TI - Ancestral divergence of Rickettsia bellii from the spotted fever and typhus groups of Rickettsia and antiquity of the genus Rickettsia. AB - The eubacterial genus Rickettsia belongs to the alpha subgroup of the phylum Proteobacteria. This genus is usually divided into three biotypes on the basis of vector host and antigenic cross-reactivity characteristics. However, the species Rickettsia bellii does not fit into this classification scheme; this organism has characteristics common to both the spotted fever group and the typhus group biotypes and also exhibits some unique features. Sequences of the 16S rRNA and 23S rRNA genes from Rickettsia rickettsii (spotted fever group), Rickettsia prowazekii (typhus group), and R. bellii were studied to determine the position of R. bellii in the rickettsial classification scheme. The 23S rRNA gene sequences described in this paper are the first 23S rRNA sequences reported for any member of the Rickettsiaceae. The 23S rRNA gene contains substantially more phylogenetic information than is contained in the 16S rRNA sequences, and the 23S rRNA gene sequence has diverged about 1.9 times faster in the three Rickettsia species which we studied. Taken together, the molecular data obtained from the two genes indicate that R. bellii is not a member of either the spotted fever group or the typhus group; rather, this organism appears to be the product of a divergence which predates the separation of the genus into the spotted fever group and the typhus group. Consequently, different combinations of the ancestral characteristics retained by R. bellii have been retained in the more derived lineages of the genus.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7981107 TI - The phylogeny of the genus Clostridium: proposal of five new genera and eleven new species combinations. AB - The 16S rRNA gene sequences of 34 named and unnamed clostridial strains were determined by PCR direct sequencing and were compared with more than 80 previously determined clostridial sequences and the previously published sequences of representative species of other low- G + C-content gram-positive genera, thereby providing an almost complete picture of the genealogical interrelationships of the clostridia. The results of our phylogenetic analysis corroborate and extend previous findings in showing that the genus Clostridium is extremely heterogeneous, with many species phylogenetically intermixed with other spore-forming and non-spore-forming genera. The genus Clostridium is clearly in need of major revision, and the rRNA structures defined in this and previous studies may provide a sound basis for future taxonomic restructuring. The problems and different possibilities for restructuring are discussed in light of the phenotypic and phylogenetic data, and a possible hierarchical structure for the clostridia and their close relatives is presented. On the basis of phenotypic criteria and the results of phylogenetic analyses the following five new genera and 11 new combinations are proposed: Caloramator gen. nov., with Caloramator fervidus comb. nov.; Filifactor gen. nov., with Filifactor villosus comb. nov.; Moorella gen. nov., with Moorella thermoacetica comb. nov. and Moorella thermoautotrophica comb. nov.; Oxobacter gen. nov., with Oxobacter pfennigii comb. nov.; Oxalophagus gen. nov., with Oxalophagus oxalicus comb. nov.; Eubacterium barkeri comb. nov.; Paenibacillus durum comb. nov.; Thermoanaerobacter kivui comb. nov.; Thermoanaerobacter thermocopriae comb. nov.; and Thermoanerobacterium thermosaccharolyticum comb. nov. PMID- 7981108 TI - Comparative analysis of the 16S rRNA gene sequence of the putative agent of proliferative ileitis of hamsters. AB - Proliferative ileitis of hamsters is consistently associated with the presence of intracellular bacteria in affected ileal epithelial cells. The 16S rRNA gene sequence of the putative etiologic agent of proliferative ileitis was determined by using cell culture-maintained organisms. The highest level of relatedness (98.4%) was observed with a newly described obligately intracellular bacterium obtained from porcine intestines, and the level of homology with Desulfovibrio desulfuricans was 87.5%. PMID- 7981109 TI - Comparison of 16S rRNA genes within the T960 and parvo biovars of ureaplasmas isolated from humans. AB - Two-by-two sequence alignment revealed that the levels of homology between 16S rRNA gene sequences of strains belonging to the two biovars of Ureaplasma urealyticum (class Mollicutes) ranged from 98.5 to 98.9%. Within the biovars, three serovars of the T960 biovar exhibited levels of homology of > or = 99.7%, and the four serovars of the parvo biovar exhibited levels of homology of > or = 99.7%. A dendrogram of the Mycoplasma pneumoniae-Ureaplasma clade of the Mollicutes reflected the distinctiveness of the biovars. PMID- 7981110 TI - Synonymy of Candida methylica with Candida boidinii and of Candida methanolophaga with Candida succiphila. AB - Some Candida species which can use methanol as a sole carbon source were studied by performing chemotaxonomic tests; we determined the ubiquinone systems of these organisms, their DNA base compositions, their electrophoretic karyotypes, and their DNA relatedness values. The type strains of Candida methanolophaga and Candida succiphila had similar DNA base compositions and exhibited 90% DNA relatedness. All Candida boidinii and Candida methylica strains had DNA G + C contents of 30.8 to 31.0 mol%, and these organisms exhibited 87 to 101% DNA relatedness to the type strain of C. boidinii. We propose that C. methanolophaga and C. methylica should be synonyms of C. succiphila and C. boidinii, respectively. PMID- 7981111 TI - Proposal of minimal standards for describing new species of the family Campylobacteraceae. AB - The International Committee on Systematic Bacteriology Subcommittee on the Taxonomy of Campylobacter and Related Bacteria has agreed in principle on minimum requirements for the description of new species of the family Campylobacteraceae. These requirements, as well as methods for determining specific characteristics, are proposed as minimal standards for the description of new species. In addition to specified phenotypic characteristics, molecular data are required. The placement of a new species should be consistent with the current view on classification usually based on methods such as nucleic acid sequencing, hybridization, or protein fingerprinting. PMID- 7981112 TI - [Kidney transplantation in children--with special reference to nursing]. PMID- 7981113 TI - [Care of children after kidney transplantation]. PMID- 7981114 TI - [Psychosocial long-term care as shown in children after kidney transplantation]. PMID- 7981115 TI - [Pediatric home care--continuing education course]. PMID- 7981116 TI - [Midwives and pediatric nurses in the delivery room. Learn from each other]. PMID- 7981117 TI - [The life of the child before birth]. PMID- 7981118 TI - [Reduced earning capacity: what does the legal pension insurance pay?]. PMID- 7981119 TI - [Educational concept--of the German education council for the nursing professions]. PMID- 7981120 TI - The short-chain alcohol dehydrogenase superfamily: variations on a common theme. AB - Multiple alignment of members of the short-chain alcohol dehydrogenase (SCAD) superfamily, according to the conserved domains A-F, has revealed a number of important relationships. It can be shown that the 17 beta-hydroxysteroid dehydrogenase type 2 enzyme is more closely related to D-beta-hydroxybutyrate dehydrogenase than it is to 17 beta-hydroxysteroid dehydrogenase type 1. Carbonyl reductase, previously considered to be a member of the aldo-keto reductase superfamily, displayed high homology in the conserved domains and is clearly part of the SCAD superfamily despite the insertion of a large peptide between conserved domains. Alignment of the product of the Leishmania methotrexate resistance gene HMTX showed that an internal, highly conserved domain can be substituted by an unrelated sequence without loss of biological activity. Furthermore, comparisons of the chimeric trifunctional enzyme enoyl-CoA hydratase/3-hydroxyacyl-CoA dehydrogenase/3-hydroxyacyl-CoA epimerase with other family members suggests that the region between the conserved B and C domains is the last to diverge between closely related enzymes and that the F domain appears to evolve with a different evolutionary clock to the rest of the protein. Finally, a highly conserved pattern of serine and threonine residues in the active site of SCAD enzymes indicates that these residues may play an important role in catalysis. These observations should facilitate alignment of future members of the SCAD superfamily. PMID- 7981122 TI - The 1,25-dihydroxyvitamin D3 (VD) analogues MC903, EB1089 and KH1060 activate the VD receptor: homodimers show higher ligand sensitivity than heterodimers with retinoid X receptors. AB - The nuclear receptor for 1,25-dihydroxyvitamin D3 (VD), VDR, belongs to the nuclear receptor superfamily. This ligand-inducible transcription factor mediates the genomic VD signalling pathways by binding to specific response elements in the promoter region of VD regulated genes. Two types of natural VD response elements are used as models for the VDR-mediated transcriptional activation: one is bound by VDR-homodimers and is found in the human osteocalcin gene promoter, and the other is bound by heterodimers of VDR with retinoid X receptors (RXRs) as in the mouse osteopontin promoter. Here, we demonstrate that the VD analogues MC903, EB1089 and KH1060, previously shown to be potent regulators of proliferation and differentiation, are able to act as ligands for VDR and replace VD as a ligand in both nuclear signalling pathways. We found that they have different potency and sensitivity in their ability to stimulate the hormone dependent promoter element. MC903 and EB1089 provide about 20% higher induction of gene activity than VD in a gene reporter system, whereas KH1060 was more sensitive, inducing transcription at about 100-fold lower doses than VD. Interestingly, VD and its analogues induce VDR homodimer-mediated gene activity at a 3- to 4-fold lower concentration than that of VDR-RXR heterodimers. This suggests that the ligand concentration is an additional regulatory level in the discrimination between signalling pathways involving homo- and heterodimeric hormone receptors. PMID- 7981121 TI - Hormonal regulation of hypothalamic gene expression: identification of multiple novel estrogen induced genes. AB - Estrogen (E) has been shown to play a major role in hypothalamic function and is a prerequisite for progesterone (P) induced sexual behavior in female rats. In the course of studies in search of steroid induced hypothalamic genes, we discovered a surprisingly large number of E-induced genes (21 mRNAs in total). This is the largest number of E-induced genes ever identified in a single organ. Many of these mRNAs exhibit considerable magnitudes of induction and their levels were maintained typically during subsequent P treatment. Among the induced genes, several encode metabolic enzymes and may account for some of the morphological changes observed in hypothalamic neurons in response to E. Since E appears to play a major role in defining the pattern of hypothalamic gene expression in conjunction with its capacity for behavioral modulation, these newly identified cDNAs may serve as genetic markers for correlative studies of E-induced central nervous system behavior. PMID- 7981123 TI - Microtubules are not required for glucocorticoid receptor mediated gene induction. AB - Steroid-free glucocorticoid receptors are generally considered to reside in the cytoplasm of cells. After the binding of steroids, the receptors translocate into the nucleus in a manner that has been proposed to involve microtubules. However, some results with inhibitors of microtubule assembly argue to the contrary. In all of these studies, only the whole cell localization of receptors has been examined; the biological activity of these receptors has not been determined. We now report that steroid-induced gene expression is maintained in the absence of intact microtubules. This argues that microtubules are not required for either the nuclear translocation or biological activity of glucocorticoid receptors. PMID- 7981124 TI - Post-transcriptional action of ACTH in the control of P450c17 expression in rabbit adrenal glands. AB - Stimulation of transcription of the CYP17 gene by ACTH has been demonstrated previously by others using cultures of adrenal tissue from several species. In the present investigations we have demonstrated from measurements in pooled rabbit adrenal glands that after 4 or 6 days of ACTH injections no difference in amounts of CYP17 mRNA per microgram of total adrenal RNA was observed between ACTH and control animals. While the total amount of CYP17 mRNA per adrenal increased 1.4- to 1.7-fold over the injected and non-injected controls due to an increase in total RNA in the ACTH-stimulated adrenals, Western analysis of adrenal microsomal protein demonstrated that the amount of adrenal P450c17 protein, the product of the CYP17 gene, increased over 50-fold. The data show that ACTH is acting at both transcriptional and post-transcriptional loci to increase the amount of rabbit adrenal P450c17 and that the greater effect is post transcriptional. PMID- 7981125 TI - Human and rat peroxisome proliferator activated receptors (PPARs) demonstrate similar tissue distribution but different responsiveness to PPAR activators. AB - We have isolated a human peroxisomal proliferator activated receptor (hPPAR) from a human liver cDNA library. Based on sequence analysis, we have determined that this cDNA encodes the human PPAR alpha. When assayed in a reconstituted hPPAR responsive transcription system in mammalian CV-1 cells, this receptor was shown to be transcriptionally activated by hypolipidemic agents like clofibric acid, and ETYA (5,8,11,14-eicosatetraynoic acid; a synthetic arachidonic acid homolog). When analyzed in CV-1 cells, the rat PPAR alpha was similarly transcriptionally regulated. However, when assayed in a human liver cell line (HepG2) we noticed that ETYA was a more efficient activator of hPPAR alpha than rPPAR alpha. Thus, factors other than the receptor are important in determining the cellular responsiveness to this class of compounds. Interestingly, WY-14,643, another peroxisome proliferator, was a much more potent activator of rPPAR alpha than human PPAR alpha when assayed in both cell lines. This may explain in part why certain fibrates are potent hepatocarcinogens in rodents. Northern analysis indicates that hPPAR alpha and rPPAR alpha are well expressed in heart, kidney and liver. We further demonstrate that hPPAR alpha and human retinoid X receptor alpha synergistically interact to bind and transactivate through a peroxisomal proliferator response element. Thus in a similar cell and promoter context the rat and human PPARs show a differential response to certain activators. Cumulatively these data suggest that differential ligand responsiveness does not provide a complete explanation for the different biological effects exhibited by hypolipidemic drugs when administered to humans and rats. PMID- 7981126 TI - Steroid gradients across the cancerous breast: an index of altered steroid metabolism in breast cancer? AB - The concentrations of 17 beta-estradiol, estrone, testosterone (T), dehydroepiandrosterone (DHEA), dehydroepiandrosterone sulphate, androstenedione (A), cortisol and prolactin (PRL) were determined in the peripheral venous blood and in the lateral thoracic vein of 14 premenopausal and 34 postmenopausal women who underwent surgery for a breast carcinoma. The difference between the two blood samples, defined as concentration gradient across the cancerous breast, was calculated for all hormones. A significant peripheral-local concentration gradient was found for DHEA and A both in pre- and postmenopausal patients, whereas for T it was observed only in postmenopausal subjects. Furthermore, DHEA and A gradients were correlated to the presence of estrogen receptors as determined by a radioligand binding assay. An inverse relationship between DHEA gradient and the expression of estrogen receptors was observed in premenopausal women, whereas in postmenopausal patients an opposite, although not significant, trend was found. These results suggest that in the cancerous breast: (1) DHEA, A and T (the latter only in postmenopause) could be taken up from plasma, and thus there could be a storage of these steroids inside the breast tissue and/or perhaps some alterations in their local metabolism; (2) androgens could play a different role in breast carcinogenesis in relation to the estrogen circulating levels and to the expression of estrogen receptors. PMID- 7981127 TI - Biochemical parameters in the anterior pituitary during the course of tumorigenesis induced by diethylstilbestrol treatment. AB - Treatment of F344 rats with diethylstilbestrol (DES) for 1-2 months induces a prolactin (PRL)-secreting pituitary adenoma. After 8 weeks of DES treatment, we have shown that the ratio of regulatory subunits of the cAMP-dependent protein kinase (RI/RII) increased in the tumors. Presently we report the variations in RI/RII ratio, pituitary weight, DNA content, serum PRL, nuclear estrogen receptor (E2R) and of ornithine decarboxylase (ODC) activity from the time of DES pellet implantation until 8 weeks. Pituitary weight, DNA content and serum PRL rose significantly at 4 weeks with a maximum at 6-8 weeks, and significantly correlated with each other. E2R and ODC activity increased from week 1 onwards, with a maximum at 2 weeks and decreased at 8 weeks. Both variables showed a positive correlation but neither E2R nor ODC activity correlated with pituitary weight, DNA or serum PRL. Values for RI remained stable with time, but RII decreased progressively. The RI/RII ratio was maintained around unity between 1-4 weeks, increasing to 1.6-2 thereafter. This ratio positively correlated with pituitary weight and DNA. It is suggested that during tumor induction by estrogen in a sensitive strain of rats, growth signals with different time-courses become activated. Increases in pituitary weight and DNA content, indicators of mammotroph hypertrophy and hyperplasia, were preceded by early rises in E2R and ODC activity. Increases in the RI/RII ratio accompanied the adenomatous change, suggesting their role in cell transformation after 6 weeks of estrogen exposure. PMID- 7981128 TI - Androstenedione stimulates progesterone production in corpora lutea of pregnant rats: an effect not mediated by oestrogen. AB - To determine if androstenedione, an aromatizable androgen, has a direct effect on luteal progesterone secretion, collagenase-dispersed luteal cells or whole corpora lutea from pregnant rats were incubated in the presence of the androgen. Luteal cells from 15-day pregnant rats responded to androstenedione in a dose dependent manner, with an increase in progesterone output at doses of 1 and 10 microM, but with no effect at minor doses of the androgen. Luteal cells obtained from animals on day 4, 9, 15 or 19 of pregnancy and incubated with 10 microM of androstenedione, increased progesterone production by 243, 39, 84 and 146%, respectively. Androgens (androstenedione, testosterone or dihydrotestosterone) but no oestrogens (oestradiol or diethylstilboestrol) at a dose of 10 microM, stimulated progesterone production in incubated luteal cells obtained from 15-day pregnant rats. The time-course pattern of androstenedione-induced progesterone production was studied by superfusion experiments using corpora lutea from rats on day 15 of pregnancy. A significant progesterone output was observed when androstenedione, but not oestradiol, was perfused through the luteal tissue. Intrabursal ovarian administration of androstenedione (10 microM) to 19-day pregnant rats induced a significative increase in serum progesterone levels 8 and 24 h after treatment. These in vivo results confirm the stimulatory effect of androstendione on progesterone production obtained in incubated luteal cells from pregnant rats. This study reports a direct luteotrophic effect of androstenedione in rat corpus luteum, not mediated by previous conversion to oestrogens. PMID- 7981129 TI - Progesterone metabolism by guinea pig intrauterine tissues. AB - Progesterone metabolism by guinea pig amnion, chorion, myometrium, and endometrium was studied at the following gestational stages. Day 45 represents mid-gestation, about 5 days before strong chorion interaction between the entire surface of the chorion and the uterus; days 57-58, 1-2 days after chorion attachment, and 2-3 days before the onset of pubic symphysis relaxation; days +1 +6, 1-6 days after the onset of pubic symphysis relaxation, i.e. within 1 week of parturition. The high metabolic activity of chorion exceeded that by amnion at all stages. Metabolism by endometrium and myometrium was always low. Conversion of progesterone by amnion significantly decreased (P < 0.05) between days 57-58 and days +1-+6. Progesterone metabolites produced by chorion and amnion were identified by TLC, HPLC, and capillary GC/MS. Both tissues converted progesterone to three major products during 60-min incubations. These were 5 alpha-pregnane 3,20-dione, 3 alpha-hydroxy-5 alpha-pregnan-20-one, and 3 beta-hydroxy-5 alpha pregnan-20-one. The metabolite pattern differed between the two tissues. Three minute incubations with chorion resulted in a significantly higher proportion of 3 alpha-hydroxy-4-pregnen-20-one (P < 0.01) and 5 alpha-pregnane-3,20-dione (P < 0.025) than at 60 min. The production of 3 beta-hydroxy-5 alpha-pregnen-20-one by chorion decreased (P < 0.05) between days 50-51 and 57-58. The ratio of 3 alpha hydroxy-5 alpha-pregnan-20-one to 3 beta-hydroxy-5 alpha-pregnan-20-one increased (P < 0.05) between days 45 post-relaxation. The marked conversion of progesterone by chorion, or the formation of one or more of its metabolites, may serve to influence uterine function prior to delivery. PMID- 7981130 TI - Consequences of challenge infections with Fasciola hepatica on rat liver P450 dependent metabolism of sex hormones. AB - The effect of single or repetitive fluke-infections on rat liver steroid hormone metabolism was studied. Fascioliasis was induced by oral administration of 20 metacercariae of Fasciola hepatica to rats, by week-6 (mono-infected) or 12 and 6 (bi-infected), or 12, 9 and 6 (tri-infected) before killing. Total microsomal cytochrome P450 and P450 isoenzymes were measured spectrophotometrically and by Western-blot analysis, respectively. Progesterone and testosterone metabolism were quantified by normal phase high performance liquid chromatography. In control rats, progesterone and testosterone were mainly converted to 2 alpha- and 16 alpha-hydroxymetabolites. In the liver of mono-infected rats, hepatic cytochrome P450 was significantly decreased by 36-64% whereas the expression of all investigated isoenzymes was decreased by 36-82% with the exception of the unchanged P4502E1. 16 alpha- and 2 alpha-hydroxylations of progesterone and testosterone were significantly decreased by 50-90%, these decreases were correlated with those of P4502B1/2 and P4502C11 isoenzymes, respectively. In bi- and tri-infected rats, steroid hormones were metabolized similarly to control rats. The return of steroid drug metabolizing enzyme activities to control level could be related to the immune response associated to the development of the animal resistance to the parasitic infection. PMID- 7981131 TI - Distinct forms of hepatic androgen 6 beta-hydroxylase induced in the rat by indole-3-carbinol and pregnenolone carbonitrile. AB - The ability of indole-3-carbinol (IC), an anticarcinogen present in cruciferous vegetables, to induce CYP1A1, CYP1A2, CYP2B1/2, CYP2E1 and CYP3A1/2 in female rat liver was determined by Western analysis using monoclonal antibodies and compared to effects produced by pregnenolone carbonitrile in animals of both sexes. The ontogeny of induction of these cytochrome P450 isozymes in response to oral administration of IC was also investigated. An inverse correlation was observed between the 6 beta-hydroxylation of androsterone (A) and the induction by IC of CYP3A1/2, the P450 isozyme responsible for the bulk of hepatic 6 beta hydroxylation of 4-androstenedione (AD). The effect of inhibitors on the formation of 6 beta-OHA from A or AD was also determined and shown to differ from their action on the P450 isozymes involved in the formation of the 6 beta hydroxylated derivatives of AD or lithocholic acid. The results indicate that the enzyme induced by IC is distinct from the CYP3A1/2 which catalyzes hydroxylations at position 6 beta, allylic in AD but not in the fully saturated ring system of A. The increased hepatic conversion of A to its biologically less active 6 beta OHA metabolite after treatment of female rats with IC could possibly contribute to the anticarcinogenic action of indole carbinols. It is also proposed that the action of multiple inducers present in cruciferous and other vegetables might produce androgen metabolic profiles very different from those produced by individual components isolated from them. PMID- 7981132 TI - Quantitative measurement of DNA content in gastric carcinoma; flow cytometry and video image analysis. AB - The DNA content of 48 gastric carcinomas from archival material was analysed by static and flow cytometry. By image analysis 81.3% of the tumours were aneuploid and ploidy was related to stage (P = 0.024) and lymph node metastasis. A trend for better survival (> 12 months) was observed in patients with diploid tumours (P = 0.058). The mean 5c exceeding rate (5cER) was significantly related to tumour stage (P < 0.05) and patient's survival (P = 0.018). In contrast, by flow cytometry only 43.7% of these tumours were aneuploid and these were more often associated with lymph node metastasis (59.3%) but no relationship was observed with any other parameters or patient's survival. In this series, image analysis appears to be more sensitive than flow cytometry in detecting small aneuploid populations. It may give additional prognostic information. It is, however, a time-consuming technique. PMID- 7981133 TI - Image analysis as a tool for quantitative enzyme determination at the cellular level: application for monocytic differentiation of the UM-384 cell line. AB - Image analysis has been used to determined enzyme activity at the cellular level in individual smeared cells. The counterstains used to visualize smeared cells were chosen to avoid overlap with the chromogene. The amount of the reaction product was quantified by computerised scanning cytophotometry when the conditions of incubation, time and temperature of the reaction, and substrate concentration varied. Under optimal conditions for time, temperature and substrate concentration, a linear relationship was found between enzyme activity determined on smeared cells and in cell lysate. Using these defined conditions, differentiation of UM-384 cells was studied by measuring enzyme activity. After a monocytic differentiation process, induced by sodium butyrate, non-specific esterase cell activity was compared either with differentiation markers (HLA-DR, plasminogen activator inhibitor type 2 and lysozyme) or with markers of proliferation (DNA content) or functional properties (nitroblue tetrazolium reduction and phagocytosis). The results show that, using image analysis, non specific esterase seems to be a useful means for the assessment of monocytic differentiation whereas myeloperoxidase is not. More generally, quantification of enzyme activity at the cellular level using image analysis can be applied to the study of the differentiation process and may help in the classification of leukemic cells. PMID- 7981134 TI - Quantitative evaluation of AgNOR in liver cells by high-resolution image cytometry. AB - This study is aimed at determining the relationship between polyploidy and the amount of nucleolar organiser region (AgNOR) positive dots or aggregates using high resolution image analysis. Liver imprints from mice in which hepatocyte polyploidy is very well documented and related to variation in nuclear area were used as a model for this investigation. A technical variant of the AgNOR method using a Triton X-100 treatment was developed for removal of some proteins from the cytoplasm, which produced a clearer and cleaner background. Feulgen-stained preparations were used to detect the association of various ploidy degrees with their respective values of nuclear area and to subsequently furnish a basis for the association of the nuclear areas in AgNOR-stained cell preparations with different ploidy levels. A high correlation between nuclear and AgNOR-stained areas was revealed and was demonstrated to be much higher than the correlation between nuclear area and the number of AgNOR positive dots or aggregates. The use of two different thresholds for segmentation of the grey levels of the AgNOR stained material demonstrated the importance of the appropriate decision to obtain the best results to be associated with polyploidy in terms of the real biological event involved, the nuclear area being in this case correlated to Feulgen-DNA values. PMID- 7981135 TI - Modelling the pattern of cell distribution around implanted materials. AB - The analysis of the cellular soft tissue response has traditionally focused on using highly skilled human assessment to determine the severity or presence of a particular type of response. This has taken the form of many different assessment criteria, some even attempting some form of 'quantitative' grading index. With the complexity of this response and the availability of high performance computer systems it is not sufficient and no longer necessary to describe a tissue response subjectively. The soft tissue response to a number of implanted materials has been analysed using a combination of immunohistochemistry and image analysis to reproducibly stain and count the cells involved in a soft tissue response to implanted materials, as well as measure their position relative to the implanted material. The combination of cell count and pattern of cell distribution revealed that although the magnitude of the cellular responses changes with respect to time the position of cells with respect to an implanted material does not change significantly over time. The position of cells is controlled more by the type of implant material and the change in subject the material is implanted in. PMID- 7981136 TI - Improvements in visualisation and localisation of human papillomavirus DNA in CaSki cells by fluorescence in situ hybridization, laser scanning confocal microscopy and three-dimensional image reconstruction. AB - The visual interpretation and localisation of specific DNA sequences in three dimensions in cell nuclei was investigated by fluorescence in situ hybridization (FISH) and laser scanning confocal microscopy (LSCM) using CaSki cells containing 600 copies per cell of human papillomavirus (HPV) DNA type 16 integrated in cellular DNA. Biotinylated DNA probes were used and DNA-DNA hybrids were revealed by a three-step reaction involving a rabbit anti-biotin antibody, a biotinylated goat anti-rabbit antibody and a streptavidin-fluorescein isothiocyanate complex. The DNA from cell nuclei was counterstained with propidium iodide. With standard fluorescence microscopy, some dense fluorescent spots were seen in the cell nuclei. Similarly, with LSCM, some hybridization spots were observed in the cell nuclei but they were at different levels of the nuclei as shown by successive nuclear sections taken along the z axis. The visualisation of multiple hybridization spots confirmed the presence of multiple integration sites of HPV 16 DNA in CaSki cells. Association of LSCM with three-dimensional reconstructions lead to spatial images of hybridization spots obtained by stacking (x,y) images from consecutive confocal planes. Rotation of the reconstructed cell nuclei around the y axis makes it possible to distinguish closely adjacent spots. The combination of these techniques improves the detection of hybridization spots and may be of interest to further determine whether the HPV DNA is episomal or integrated in infected cells. PMID- 7981137 TI - Megakaryopoiesis in chronic myeloproliferative disorders: immunohistochemical evaluation of endoreduplicative activity by PCNA-staining reaction. AB - A morphometric analysis has been performed on bone marrow trephine biopsies following sequential double-immunostaining with monoclonal antibodies PC10 (anti proliferating cell nuclear antigen--PCNA) and Y2/51-CD61 (anti-platelet glycoprotein IIIa) to evaluate endoreduplicative activity of megakaryopoiesis. In addition to a control group, patients included different subtypes of chronic myeloproliferative disorders (CMPDs) like chronic myeloid leukaemia (CML), polycythaemia vera (P. vera), primary thrombocythaemia (PTH) and finally primary (idiopathic) osteomyelofibrosis (OMF). In comparison with the normal bone marrow and also with P. vera and PTH a significant increase in PCNA-labelling (late G1 and S phases) of megakaryocytes was recognizable in OMF, contrasting with a striking reduction of this marker in CML. Particularly in advanced stages of OMF, secondary folate deficiency leading to a megaloblastoid appearance of erythroid precursors is a frequent finding. In pernicious anaemia previous cytokinetic studies have demonstrated an arrest in the S phase (DNA synthesis) of the cell cycle due to vitamin B12/folate (haematinic) deficiency. A similar pathomechanism may also be effective in OMF. Consequently, a block in the S phase of the cell cycle is assumed which is in keeping with the increased numbers of PC10-positive megakaryocytes. Significant correlations were calculable between megakaryocyte sizes and PCNA-staining capacity in the normal bone marrow and CMPDs. According to morphometry small-sized (hypoploid) megakaryocytes showed a prevalence of PCNA labelling. This finding is confirmative with a hypothesis on the dynamics of endoreduplicative activity of megakaryocytes, i.e. the prolongation of G1/G2 phases in larger (polyploid) elements. On the other hand, some of the giant polyploid megakaryocytes may cease endoreduplication and enter into G0 phase, which could partially explain the predominance of PCNA-negative large-sized cells of this lineage. PMID- 7981138 TI - Evaluation of AgNOR and Ki-67 antigen as cell kinetic parameters in oral dysplasias and carcinomas. AB - The mean numbers of argyrophil nucleolar organizer regions (AgNORs) and the Ki-67 antigen expression as proposed cell kinetic parameters were evaluated in 80 biopsies of suspected oral dysplasias and 40 probes of oral squamous cell carcinomas. No statistical relationship was found between the mean numbers of AgNORs and nucleoli per cell. However, the mean numbers of AgNORs per nucleus and the percentages of cells in S-phase as determined by flow cytometry show a correlation. Related to the histological degree of dysplasia, both AgNOR counts and percentages of cells in S-phase reveal a similar pattern of distribution. With values widely spread, the percentages of Ki-67 positive cells increase according to the histopathological degree of malignancy. Also, a correlation between the percentages of Ki-67 positive cells and cells in S-phase was evident. Therefore, both the AgNOR counts and the Ki-67 antigen are considered to be valuable tools for cell kinetic reference and can be considered supplementary methods to flow cytometry in diagnosis and therapy of oral cancer. PMID- 7981139 TI - An autoantibody derived from mice with experimental systemic lupus erythematosus is directed against the essential splicing factor SF53/4--a possible role for large nuclear ribonucleoprotein particles in autoimmune disorders. AB - We have previously shown that nuclear transcripts of several pre-mRNAs can be released from nuclei of mammalian cells in a form of large nuclear ribonucleoprotein (InRNP) particles. These particles, which invariably sediment at the 200S region in sucrose gradient, contain all U small nuclear RNPs required for pre-mRNA splicing and a multitude of heterogeneous nuclear RNP proteins. From a panel of mAbs raised against the InRNP particles, a specific mAb (53/4) identified a nuclear protein of 88 kDa as an essential splicing factor (SF53/4). In a parallel independent study, mAbs were established in mice with experimental systemic lupus erythematosus (SLE), that had been induced by immunization with a murine mAb against a human anti-DNA mAb bearing the common 16/6 idiotype. One of the produced mAbs (2C5/3) recognized an 88 kDa RNP protein. In the present study we have used the following criteria to demonstrate that mAb 2C5/3 and mAb 53/4 recognize the same protein. First, mAb 2C5/3 inhibited splicing by direct addition. Second, the 88 kDa polypeptide that had been immunodepleted from HeLa cells nuclear extract by mAb 2C5/3 was recognized by mAb 53/4 in protein blots. Third, the HeLa nuclear extract depleted by mAb 2C5/3 was devoid of splicing activity and could not assemble into splicing complexes with exogenous pre-mRNA; however, splicing and spliceosome assembly activities were restored to such a defective extract by adding back the 88 kDa protein that had been purified by immunoaffinity binding to immobilized mAb 53/4.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7981140 TI - Changes in the subsets of CD4+ T cells in Trypanosoma musculi infection: delay of immunological cure in young mice and the weak ability of aged mice to control the infection. AB - After a 3 week course (approximately), during which there is marked lymphoid hyperplasia, Trypanosoma musculi infections in young-adult mice are cured by an immune mechanism involving antibodies of the IgG2a isotype. Both the lymphoid hyperplasia and IgG2a antibody response are T-cell-dependent events and both processes appear to be defective in aged mice. The purpose of the studies reported here was to elucidate the effects of T. musculi infection on subsets of T cells for two reasons: (i) to gain insight into the probable roles of selected cytokines (IL-2, IL-4 and IFN-gamma) in facilitating the production of curative, IgG2a antibodies, and (ii) to examine the hypothesis that aging affects the competence of CD4+ T cells to participate in immunological control of infections. The major conclusions from these studies are that: (i) T. musculi infection of mice induces rapid change in the CD4+ T cell population toward predominance of the activated or memory (CD45RBloCD44hi) phenotype, cells which produce IFN gamma, II-3, IL-4 and IL-5, accompanied by profound inhibition of IL-2 production, and (ii) in the old mice these changes are superimposed on the natural age-associated changes in the same direction (i.e. toward predominance of CD45RBloCD44hi T cells). Thus, in the old animals, the combined changes of aging and infection, moving in the same direction, are devastating, resulting in the aged animals being unable, or barely able, to control infection. PMID- 7981141 TI - The Xid defect determines an improved clinical course of murine leishmaniasis in susceptible mice. AB - The course of Leishmania major infection in B cell-defective BALB.Xid mice was investigated. Infected BALB.Xid mice showed a significantly slower lesion development compared with BALB/c controls accompanied by a 10- to 30-fold lower parasite burden in lymphatic organs. The B cell immune response, as quantified by anti-leishmanial antibody production and B cell numbers in lymphatic organs, remained significantly lower in BALB.Xid mice as compared with BALB/c control mice. In accordance with disease development, CD4+ T cells from lymph nodes of infected BALB.Xid mice produced 6- to 10-fold more IFN-gamma than the respective T cells of BALB/c mice, when stimulated with leishmanial antigen in vitro. B cells from lymph nodes and the peritoneal cavities of BALB/c mice could be induced to produce 3- to 8-fold more IL-10 than the respective cells from B cell defective BALB.Xid mice. The data thus indicate that the Xid mutation allows for the development of Th1 cells which confer resistance to infection with L. major. Moreover, the data suggest that B cells contribute to susceptibility to L. major infection in BALB/c mice by skewing the Th cell network towards a Th2 phenotype. Since the difference in B cell-derived IL-10 production between BALB/c and BALB.Xid mice was more prominent in peritoneal B cells, the data support the notion that the skewing of the T cell response may be predominantly mediated by the B1 cell subset. PMID- 7981143 TI - A bifunctional control element in the human IgE germline promoter involved in repression and IL-4 activation. AB - One of the first steps during Ig heavy chain isotype switching to IgE is the IL-4 induced synthesis of IgE germline transcripts. To further characterize the molecular mechanism of the IL-4 action, the regulatory DNA elements involved in the control of expression of these transcripts were analyzed. Transient transfection of a B cell tumor line revealed the presence of a 15 bp IL-4 responsive cis-acting element (IL-4RE) highly homologous to an IL-4 response element in the human CD23b promoter. An IL-4 induced DNA binding protein specifically interacted with this sequence. Point mutations within that sequence not only abolished IL-4 inducibility of reporter constructs but also prevented binding of the nuclear factor to the mutated sequence. A stretch of 16 nucleotides just upstream of the IL-4RE contributed to IL-4 inducibility and formed nucleoprotein complexes with constitutive factors. All reporter constructs containing the functional IL-4RE were transcriptionally very weak but could be readily activated upon IL-4 induction. Transfection of constructs containing the mutated IL-4RE or plasmids lacking that sequence displayed a high constitutive promoter activity and were IL-4 unresponsive. These data suggest that in the absence of the cytokine the activity of the IgE germline promoter is actively repressed through the action of the IL-4RE. The same sequence appears to be critically involved in the IL-4 induced activation of the promoter via the binding of a cytokine induced transcription factor. PMID- 7981142 TI - 3H11, a unique cell surface molecule involved in the function of the CD45RA+ subset of CD4+ cells. AB - We have developed a mAb anti-3H11 by immunizing mice with a T cell line derived from the Callithrix jacchus (common marmoset). Anti-3H11 is reactive with approximately 48% of unfractionated T cells, 62% of CD4+ cells and 39% of CD8+ cells. Among CD4 cells, anti-3H11 preferentially reacts with the CD45RA+ T cell subset. The majority of helper activity for pokeweed mitogen (PWM)-driven B cell IgG synthesis and T cell response to recall antigen such as tetanus toxoid was found within the 3H11-CD4 cell population, whereas anti-3H11+CD4+ cells provided poor helper function for PWM-driven B cell IgG synthesis and were more responsive to concanavalin A and autologous mixed lymphocyte reaction. Biochemical characterization showed that anti-3H11 precipitated a single protein band with a relative molecular weight of 32,000 from 125I-surface labeled cell lysate. Biochemical, phenotypic and functional studies revealed that the 3H11 molecule appeared to be different from previously established molecules on the T cell surface. Interestingly, addition of anti-3H11 to the combination of CD4 and B cells in the presence of CD8 cells but not to the combination of CD4 and B cells resulted in enhancement of the suppression of PWM-driven B cell IgG synthesis. Moreover, anti-3H11 had a co-mitogenic effect on T cells via the CD2 and CD3 pathways, and this co-mitogenic activity is restricted to the CD45RA+ T cells. Taken together, our results show that the 3H11 molecule is a novel antigen which may play an important role in the activation and function of the CD45RA+ subset of T cells. PMID- 7981144 TI - Interaction of mAb to angiotensin-converting enzyme (ACE) with antigen in vitro and in vivo: antibody targeting to the lung induces ACE antigenic modulation. AB - We previously described that mAb to angiotensin-converting enzyme (ACE), mAb 9B9, accumulates in the rat lungs after systemic injection. In the present work we have documented that mAb 9B9 cross-reacts with human, monkey, rat, cat and hamster ACE, while other ACE antibodies did not cross-react with the rat, cat and hamster enzyme. Anti-ACE mAb 3A5 and I2H5 inhibit human ACE in vitro, while mAb 9B9 does not inhibit ACE activity. Radiolabeled mAb 9B9, but not other antibodies, accumulates selectively in rat, cat and hamster lungs after systemic administration. No accumulation of mAb 9B9 has been observed in hamster kidney, while hamster kidney ACE activity is higher than that in the lung. mAb 9B9 does not induce complement-mediated injury to cultured endothelial cells. No pathological changes were detected in organs of animals after mAb 9B9 injection (10-100 mg/kg). However, injection of these amounts of mAb 9B9 leads to a decrease in ACE activity in the lung homogenates and an increase in serum. In cultured human endothelial cells treatment with mAb 9B9 increases ACE activity in cell medium and decreases in cell lysates. Therefore, while mAb 9B9 does not kill endothelial cells, at high dose it may induce ACE shedding from the cell. The results obtained support the potential of anti-ACE mAb 9B9 for targeting to the lung and for investigations of the pulmonary endothelium. PMID- 7981145 TI - An improved system of somatic cell molecular genetics for analyzing the requirements of Ig synthesis and function. AB - A general method of relating molecular function and structure is to examine the biological and chemical effects of defined mutations. In many cases, particularly those concerned with the rate or efficiency of gene expression, it is important to assess mutations in the normal chromosomal context. There are two methods of obtaining such mutants: (i) site-directed mutagenesis of the chromosomal locus, using homologous recombination to target defined mutations to the gene of interest, and (ii) phenotypic selection of mutant organisms. For most mammalian genes the rarity of targeted recombinants and phenotypically evident mutants impede the use of either of these approaches. However, various genetic and biochemical features render the Ig heavy chain locus in B cell lines amenable to both gene targeting and phenotypic selection of mutants. We describe here a replacement-type vector in which the selectable marker is an enhancerless gpt gene which is particularly suitable for targeting the IgH locus. Deletion of the enhancer greatly decreased the frequency of gpt+ random transformants while still allowing properly targeted transformants to be gpt+, such that transformants with the predicted recombinant structure comprised 25% of the gpt+ population. Thus, the labor involved in mutagenizing the chromosomal locus using this method is comparable to the usual method of isolating randomly inserted transformants, but offers the important advantages that the copy number and integration site are the same in independent transformants. In the hybridoma cell lines which we have tested, the consistent copy number and integration site are sufficient to yield a uniform level of recombinant gene expression.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7981146 TI - Disregulation of Myc expression in murine bone marrow cells results in an inability to proliferate in sub-optimal growth factor and an increased sensitivity to DNA damage. AB - Derivatives of the murine bone marrow-derived, IL-3-dependent cell line, BAF3, were isolated following recombinant retroviral infection which showed disregulated expression of human c-Myc oncoprotein. Such cells entered apoptosis and lost viability more rapidly than parental BAF3 cells when IL-3 was removed. c Myc disregulation also resulted in an inability of BAF3 cells to survive in either sub-optimal concentrations of IL-3, or saturating concentrations of IL-4 and insulin-like growth factor-1. Furthermore, BAF3 cells with disregulated c-Myc expression were more sensitive to the induction of apoptosis by DNA-damaging agents. These effects of c-Myc disregulation could be inhibited by co-expression of the Bcl-2 oncoprotein. The implications of these data for the transformation of haematopoietic cells by disregulation of Myc expression are discussed. PMID- 7981147 TI - Activation of high endothelial venules in peripheral lymph nodes. The involvement of interferon-gamma. AB - The introduction of Freund's complete adjuvant into footpads of mice leads to functional changes of the high endothelial venules (HEV) in the draining lymph nodes. Using an in vitro adhesion assay, increased binding of monocytes and dendritic cells could be seen. These effects are also seen after injection of high doses of INF-gamma. No changes in the expression of vascular addressins, VCAM-1, E selection or ICAM-1 could be observed but the binding of monocytes could be blocked with an antibody against Mac-1. Depletion studies have made it clear that macrophages in the lymph node are not directly involved in the activation of the HEV. The induction of additional adhesion mechanisms on HEV could be an efficient way to recruit inflammatory cells into the lymph node, thereby regulating the local immune response. PMID- 7981148 TI - M17: a novel gene expressed in germinal centers. AB - Germinal centers are histologically distinct structures that form within the draining lymphoid tissues following immunization with T cell-dependent antigens. Here, antigen-specific B cells transform the lymphoid follicle into a site of intense B cell proliferation, differentiation and selection. To understand the molecular basis for these cellular events, we sought to isolate germinal center B cell-specific genes using subtractive cDNA libraries derived from FACS-sorted (CD45R/B220+, IgD-, Thy1.2-) lymph node B cells of immunized mice. A novel gene isolated from this library, designated M17, was found to be transcribed in spleen and, to a lesser extent, bone marrow. Strikingly, only PNA+ (germinal center) but not PNA- splenic B cells express M17. Germinal center-specific expression of M17 was confirmed by staining of histological sections of spleen with an antiserum raised against a glutathione-S-transferase-M17 fusion protein. The M17 gene comprises four exons spanning 13.2 kb, and encodes a 25 kDa cytoplasmic protein of 159 amino acids. Analysis of the amino acid sequence revealed the presence of a possible lipid binding domain and multiple potential phosphorylation sites, including a tyrosine-based activation motif. We speculate that M17 may be a signaling molecule involved in the transduction of signals from the cell surface to the cytoplasm. PMID- 7981149 TI - Split tolerance between spleen and lymph node cells in severe combined immunodeficiency mice grafted with AKR fetal liver cells. AB - Severe combined immunodeficient (SCID) mice defective in stem cells for T and B cells appear to be an ideal host for construction of chimeric mice. When bone marrow cells are used as a source of stem cells, however, host SCID mice do not always show sufficient reconstitution. In this study, fetal liver cells from AKR embryos were transplanted into SCID mice without prior irradiation. This treatment induced full reconstitution of lymphopoiesis as evaluated by flow cytometry analysis and serum Ig production 2 months after transplantation. Thus, fetal liver cells seem to be a better source for reconstitution of SCID mice than bone marrow cells. Lymph node (LN) cells of these mice (FLT mice) had no proliferative or cytotoxic activities against either host-type (C.B-17) or donor type (AKR) spleen cells. However, spleen cells from FLT mice exhibited marked proliferative and cytotoxic activities against C.B-17 cells, with no activities against AKR cells. Split tolerance against C.B-17 cells in spleen and LN cells was not a transient phenomenon, since similar results were obtained from a cytotoxic T lymphocyte assay 4 months later. In spite of the strong host reactivity in vitro, aberration of clonal deletion or development of a graft versus-host disease was not seen in FLT mice. As IL-2 induced the host reactivity of LN cells in a mixed lymphocyte reaction, potentially host-reactive T cells were present in LN but were rendered anergic. Tolerance in FLT mice seems to be regulated by a peripheral mechanism. We supposed that the split tolerance in FLT mice was induced by the different antigenicity between the spleen and LN. PMID- 7981150 TI - Identification of T cell autoepitopes that cross-react with the C-terminal segment of the M protein of group A streptococci. AB - Rheumatic fever (RF) follows a throat infection with different M-serotypes of beta-hemolytic group A streptococci (GAS) and can affect different tissues, predominantly the heart. It is thought to be an autoimmune illness. Although histological examination of affected heart shows an infiltrate consisting mainly of T cells, antigens or epitopes that could be putative targets of autoimmune T cells have not been identified. We have examined the T cell response to the conserved C-terminal region of the M protein--a streptococcal surface coiled-coil protein which is the target of opsonic antibodies and antibodies which cross react with human heart tissue. Australian Aborigine, Caucasian and Thai patients, controls and mice were studied to define regions of the protein immunogenic for T cells, and T cell lines and clones were tested for cross-reactivity to myosin as well as an extract of RF-diseased mitral heart valve. Murine (B10, B10.D2, B10.BR) M peptide-specific T cells were often cross-reactive for other M peptides but did not cross-react with human heart antigens. Patients with RF or other heart diseases, or control subjects exposed more commonly to GAS were more likely to have T cell responses to the M protein, with many regions of the C-terminus being recognized. T cell lines and a clone specific for different M peptides were generated from five donors. Cross-reactivity could be shown between different M peptides, but unlike murine M peptide-specific T cells three of the human T cell lines reacted strongly to peptides representing homologous regions of cardiac and skeletal muscle myosins, and two of these lines also responded to porcine myosin and an extract of human rheumatic mitral valve. However, these last two lines were derived from a normal donor without history of RF or other heart disease. Our data demonstrate that regions of the M protein, including regions that are being considered as subunit vaccines, have the potential to stimulate pre existing heart cross-reactive T cells, but that the ability of such T cells to cross-react (as measured in vitro) is not in itself sufficient to lead to disease. PMID- 7981151 TI - Characterization of p59fyn-mediated signal transduction on T cell activation. AB - Protein tyrosine kinase p59fyn is associated with the TCR-CD3 complex and is suggested to play a role in T cell activation. To determine the molecular mechanism of p59fyn-mediated signal transduction in T cell activation, we established murine T cell hybridoma lines that expressed an elevated amount of wild-type or mutant fyns. Clones that expressed high levels of normal p59fyn and active p59fyn, encoded by wild-type and f-14 mutant fyn respectively, showed enhanced IL-2 production upon stimulation by anti-CD3 antibodies or natural antigen. On the other hand, clones that expressed kinase negative p59fyn and p59fyn with an SH2 (Src-homology 2) deletion encoded by t-1 mutant fyn showed little induction of IL-2 production upon stimulation. These data suggest that p59fyn is important in T cell signaling and that the SH2 sequence plays a critical role in the reaction. Induction of tyrosine phosphorylation of multiple proteins upon antigenic stimulation was augmented similarly in the cells that respectively expressed wild-type and f-14 mutant fyns at elevated levels. The proteins that became highly tyrosine-phosphorylated included phospholipase C (PLC gamma 1), p95vav, ZAP-70, the MAP kinase, CD3 zeta and unidentified proteins of 120, 100 and 80 kDa. Tyrosine phosphorylation of the 120, 95 and 68 kDa proteins associated with PLC-gamma 1 was also observed in these cells upon stimulation. In contrast, only the 100 kDa protein and the MAP kinase were increasingly tyrosine phosphorylated in the antigen-stimulated cells expressing t-1 fyn. These data suggest that PLC-gamma 1, PLC-gamma 1 associated molecules, p95vav, the 80 kDa protein, ZAP-70 and the CD3 zeta chain may be substrates of p59fyn or of other tyrosine kinases regulated by p59fyn and be important in T cell signaling. PMID- 7981152 TI - IL-2 receptor alpha chain expression during early B lymphocyte differentiation. AB - The IL-2/IL-2 receptor (IL-2R) has been studied intensively because of its potential function in the development and regulation of the immune system. The IL 2R alpha chain has been shown to be expressed on CD4-CD8- thymocytes and activated T and B cells. In this report, we show that IL-2R alpha is also expressed on precursor B cells in the bone marrow. Its expression is initiated by functional rearrangement and expression of Ig mu heavy chain gene and is down regulated when immature B cells mature and express IgD. Its potential function in early B cell differentiation is discussed in comparison with its role in thymocyte differentiation. PMID- 7981153 TI - Acid sphingomyelinase is not essential for the IL-1 and tumor necrosis factor receptor signaling pathway leading to NFkB activation. AB - A recent report has suggested that tumor necrosis factor (TNF) utilizes acid sphingomyelinase (SMase) pathway to activate NFkB (Schutze et al. 1992. Cell 71:765). To directly investigate the role of acid SMase in IL-1 and TNF receptor mediated signal transduction, we examined the ability of Niemann-Pick disease (NPD) type A fibroblasts, which are deficient in acid SMase, to induce IL-8 gene expression through activating NFkB. Unexpectedly, IL-1 alpha and TNF-alpha efficiently induced IL-8 production and IL-8 mRNA in NPD type A fibroblasts as in normal fibroblasts. Furthermore, activation of NFkB was also induced in NPD type A fibroblasts in response to IL-1 alpha and TNF-alpha stimulation to a similar extent as in normal fibroblasts. These results provide evidence that acid SMase is not essential in IL-1 and TNF receptor signaling leading to NFkB activation as well as the cytokine gene activation which is regulated by NFkB. PMID- 7981155 TI - A novel initiator/promoter element within the CD45 upstream region. AB - Transcripts of the murine hematopoietic cell surface antigen CD45 (also known as Ly-5, LCA, T200 and B220) initiate at three distinct sites--P1a, P1b and P2- within the upstream region, though P1b is the major site of initiation in lymphoid cells. In our studies of the CD45 upstream region, we identified a cluster of nucleotides comprising the P2 start site, called the TC box, that acts as a minimal promoter for transcription from the P2 site. Thus, the TC box is functionally analogous to elements called initiators that direct RNA polymerases to begin transcription at specific positions. However, in contrast with other initiators, the CD45 TC box directs activated tissue specific expression. The TC initiator, therefore, may provide an effective means to achieve broad expression of exogenously introduced genes in immunologically relevant cells. PMID- 7981154 TI - Expression of the IL-2 receptor gamma chain on various populations in human peripheral blood. AB - We have established two rat mAbs, TUGh4 and TUGh5, specific for the human gamma chain of the IL-2 receptor (IL-2R), which is known to be shared among receptors for IL-2, IL-4 and IL-7. The antibodies bound to cell lines transfected with the human gamma chain gene but not to their parental cell lines, and precipitated 65 70 and 80-90 kDa cell surface molecules from lysates of human T cells surface labeled with Na125I and chemically cross-linked with [125I]IL-2 respectively. Flow cytometry with TUGh4 and TUGh5 detected the gamma chain in a wide variety of peripheral blood cell populations including CD4+ T cells, CD8+ T cells, CD20+ B cells, CD56+ natural killer cells, CD14+ monocytes and granulocytes, contrasting with expression of the alpha and beta chains of IL-2R. PMID- 7981156 TI - Biosynthesis from gluconate of a random copolyester consisting of 3 hydroxybutyrate and medium-chain-length 3-hydroxyalkanoates by Pseudomonas sp. 61 3. AB - Pseudomonas sp. 61-3 isolated from soil was found to produce a polyester consisting of 3-hydroxyalkanoic acids of even carbon numbers C4, C6, C8, C10 and C12 when sodium gluconate was fed as the sole carbon source. The polyester produced was fractionated with boiling acetone. The acetone-insoluble fraction (28 wt%) of the polyester was a poly(3-hydroxybutyrate) homopolymer, while the acetone-soluble fraction (72 wt%) was composed of seven different 3 hydroxyalkanoate (3HA) units ranging from C4 to C12: 40 mol% 3-hydroxybutyrate (3HB), 5 mol% 3-hydroxyhexanoate (3HH), 20 mol% 3-hydroxyoctanoate (3HO), 24 mol% 3-hydroxydecanoate (3HD), 1 mol% 3-hydroxy-5-cis-decenoate (3H5D), 4 mol% 3 hydroxydodecanoate (3HDD) and 6 mol% 3-hydroxy-5-cis- dodecenoate (3H5DD). The copolymer was characterized by nuclear magnetic resonance (NMR) spectroscopy, gel permeation chromatography and differential scanning calorimetry. The acetone soluble fraction of this amorphous copolymer was shown to have a random sequence distribution of the seven 3HA units of C4 to C12 by analysis of the 150 MHz 13C NMR spectrum. This is the first example of microbial synthesis of a random copolyester consisting of 3HB and medium-chain-length 3HA units. PMID- 7981157 TI - Depolymerization reactions of hyaluronic acid in solution. AB - Samples of microbial sodium hyaluronate were degraded by heating, ultrasonication ultraviolet (UV) and gamma-ray irradiation and enzymatic treatment. The weight average molecular weight, Mw, of hyaluronate in 0.15 M NaCl and 0.06 M Na2HPO4 was determined by gel filtration with UV detection. The Mw of the degraded samples varied from 8 x 10(4) to 1.38 x 10(6). Depolymerization processes can be described by linear relationship (1/Mw)2 = f(t) in the case of ultrasonic treatment and by non-linear relationships in the cases of heating and UV irradiation at 257 nm. Gamma-ray irradiation and enzymatic treatment caused chemical degradation and depolymerization to oligosaccharides, respectively. PMID- 7981158 TI - Shear modulus-temperature meltdown profiles of gelatin and pectin gels. A cascade theory description. AB - In this paper, a cascade theory approach to biopolymer gelation is developed to describe variation of the shear modulus with temperature for thermoreversible gels. The broadness of this 'melting transition' is seen to depend crucially on the enthalpy of cross-linking, while the critical gel melting temperature is determined by additional factors such as the entropy of cross-linking, the polymer concentration, the molecular weight, and the number of cross-linking sites. On using the model to fit experimental data for specific gelatin and pectin systems, it was found that the behaviour of gelatin (sharp melting transition and low melting temperature) is a consequence of the large negative enthalpy and entropy of cross-linking, while, in contrast, the broad melting transition and high melting point of the pectin system are consistent with much smaller negative values for these parameters. PMID- 7981159 TI - Study on the thermal stability of alpha-amylase modified by maleic anhydride copolymer. AB - The thermal inactivation of mesophilic Bacillus subtilis alpha-amylase modified by maleic anhydride/vinyl acetate copolymer has been studied at different polymer/enzyme ratios in the pH range of relevance to enzymatic catalysis. Enzymatic activity measurements combined with circular dichroism measurements were used to determine the enzyme thermostability. The apparent first-order rate constants and activation energies of thermo-inactivation affected by addition of Ca2+ ions as well as by modification have been calculated. The modified alpha amylase exhibited sufficiently high catalytic activity with enhanced resistance to the thermal unfolding process. PMID- 7981160 TI - Rheological study on mixtures of different molecular weight hyaluronates. AB - The shear flow of hyaluronate solutions prepared from mixtures of hyaluronates with different molecular weights has been studied. This paper shows that prediction of the rheological behaviour of polymer mixtures at a given polymer concentration is possible knowing the intrinsic viscosity of the different mixed samples and the general variation of the specific viscosity versus the overlap parameter C[eta]. These characteristics depend on the total ionic strength in solution and have been determined for three conditions: in 0.1 M NaCl and at ionic strengths corresponding to hyaluronate concentrations of 5 and 10 g l-1 in pure water. The differences between the predicted viscosities and the measured ones are usually lower than 5% for the three conditions tested. PMID- 7981162 TI - Viscosity and flow properties of concentrated solutions of chitosan with different degrees of deacetylation. AB - The effects of the degree of deacetylation (DD) on the viscosity and flow behaviour of concentrated solutions of chitosan were investigated using 0.2 M CH3COOH and 0.2 M CH3COOH/0.1 M CH3COONa aqueous solutions as solvents. The results indicated that the viscosity and flow properties of the solutions differed with the DD of chitosan. The solution viscosities and the non-Newtonian flow properties as well as the flow activation energies E gamma increased with the increasing DD of chitosan. However, the additional salt decreased the viscosities and the non-Newtonian flow properties of the solutions of chitosan, but did not change the flow activation energies E gamma of the solutions. PMID- 7981163 TI - The role of surgery and lithotripsy in childhood urolithiasis. AB - From 1982 through 1993 36 interventions in 32 infants and children with urolithiasis have been performed in our department. There were 22 boys and 10 girls. The main cause for the interventions have been congenital malformations in 9, followed by recurrent urinary tract infections in 6, previous operations in 5 and hypercalciuria in 5 patients. In 7 children the cause of the urolithiasis remained unknown. As a therapeutic option extracorporeal shock-wave lithotripsy (ESWL) was available after 1988. The malformations as well as the postoperative conditions have been corrected surgically and the calculi were removed at the same time. For post-infectious, idiopathic or hypercalciuric calculi ESWL was used in the majority of patients after 1988. Therefore a total of 26 calculi were removed by operation and 13 by ESWL. Only 1 calculus was extracted endoscopically. There were no complications either after ESWL or after open surgery. Our results show that ESWL gains more and more importance in infants and children. Calculi in congenital malformations or as result of operations are still removed by open surgery. In the other cases ESWL is the method of choice. PMID- 7981161 TI - Conformational changes in the cyclic undecapeptide cyclosporin induced by interaction with metal ions. An FTIR study. AB - Infra-red spectra have been measured for the cyclic undecapeptide cyclosporin A (CsA) and three analogues CsC, CsD and CsH in acetonitrile and in the presence of 10:1 molar excess of Mg2+, Ca2+, Na+ or Li+ in the same solvent. Interaction with each of these ions is suggested by marked changes in band positions over the amide I region (1600-1700 cm-1). The formation of complexes of cyclosporin with calcium and magnesium ions is indicated by the presence of C = O stretching bands well outside the range normally expected for the amide I absorptions of free peptides. Although they share this characteristic, the spectra indicate that the mode and/or strength of Ca2+ binding is quite different from that of Mg2+ binding. In contrast, the two monovalent ions interact with CsA, CsC and CsD to yield spectra that are very similar to one another. The spectra are consistent with binding of the monovalent ions simultaneously to several carbonyl groups of the loop structure. PMID- 7981164 TI - Urolithiasis in childhood: when to do what? AB - Between 1983 and 1992 22 children with urolithiasis were treated at the Department of Paediatric Surgery and Paediatrics of the University Hospital of Berne. There were 8 girls and 14 boys with a mean age of 7.3 years. Metabolic disease was found in 6 children. There were 12 renal stones, 12 ureteral stones, 1 bladder stone and 1 urethral stone. Conservative therapy, ESWL, and surgery were used as treatment each in one third of the children. Studying our patient group and analyzing the recent literature, the place of the different therapeutic methods of the childhood stones will be discussed. PMID- 7981165 TI - Immobilization, a risk factor for urinary tract stones in children. A case report. AB - Immobilization causes bone dissolution leading to hypercalcemia and hypercalciuria in children. We report the case of a 10-year-old boy who developed 2 stones in the pelvis off his left healthy kidney after only 8 days of immobilization. He was on bedrest after pyeloplasty done for a ureteropelvic junction obstruction on the right side. Compared to references in literature our patient showed stone formation very early during the course of immobilization. Temporary hypercalciuria and stone formation are well documented because of underlying kidney disease. The risk factors of immobilization-induced hypercalciuria and hypercalcemia are discussed together with possible treatment and prophylaxis of this pathology. PMID- 7981166 TI - Spontaneous perforation of the ureter: a rare complication of urolithiasis. AB - The spontaneous rupture of the ureter is a rare condition. A case of a girl is reported with a spontaneous perforation caused by ureteral and renal calculi. The concomitant urinoma was drained and the ureter splinted with a double-J catheter. The calculi were destroyed by extracorporal piezoelectric lithotripsy without anesthesia. PMID- 7981168 TI - Prostatic utricle: an unusual case report. AB - A 3-year-old white patient was hospitalized for the second recurrence of an epididymitis but this time with a left scrotal abscess. He was known to have a perineoscrotal hypospadias associated with bilateral undescended testis. Cystoscopy with cytourethrography releaved the presence of a "prostatic utricle". At operation after treatment of the infection the utricle was exised. Surprisingly a vagina masculinus (vagina, uterus and fallopian tubes without ovaries) more than a conventional utricle was found. PMID- 7981167 TI - Duplex ureteroceles: is radical surgery always necessary? AB - To answer the question about the best therapeutic procedure in duplex ureteroceles a prospective and retrospective study was performed. In a first group we summarized the patients operated from 1971 to 1986. These infants and children were compared to a group operated from 1987 to 1992. In the first group the operative procedure was chosen according to the presence or absence of reflux into the lower pole system. All patients with reflux were corrected radically in one operation. The control showed a reoperation rate of 45% (8 of 18 patients). 3 patients lost a functioning renal unit. In the second group the operative procedure was chosen according to the function of the upper pole. It was resected if its function was below 10% measured by DMSA-scintigraphy. In cases with functioning upper pole a pyeloureterostomy was performed. Only in two cases the ureterocele was resected primarily. In this group a second operation was necessary in only 3 of 16 patients and renal function was preserved in all cases. Our results show that radical surgery in duplex ureteroceles is seldom necessary and a staged procedure is the method of choice. PMID- 7981169 TI - Achalasia in childhood and adolescence. AB - We analysed the charts of paediatric patients suffering from oesophageal disorders in 5 departments of paediatric surgery in Switzerland from 1972-1993 finding only 16 patients with proven achalasia (0.6%). The personal history showed a wide gap of several years from the first symptoms until diagnosis and treatment due to false interpretation of symptoms. Dilatations alone have never been definitely successful. In 16 patients, a Heller's procedure was done, 2 had an additional Thal, 12 a Nissen fundoplication, one a hiatoplasty and one no antireflux procedure. 3 patients needed further postoperative dilatations for several months up to 3 1/2 years. One patient suffering from an AAA syndrome (Achalasia/Alacrimia/ACTH deficiency) did not improve after Heller's procedure with Nissen fundoplication and dilatations. We finally had to resect the oesophagus and replace it by gastric transposition. Two children were lost for long-term follow-up. In 14 patients the follow-up is more than 10 years. 14 patients take normal food and are in the normal percentiles for length and height. Achalasia in childhood shows a wide spectrum of oesophageal dysmotility. In many cases, the propulsive force might be so weak that only a very lose antireflux procedure is tolerated. Occasionally, the whole oesophagus is without appropriate function and has finally to be resected as in our patient suffering from AAA syndrome. This child is now free of clinical pathological symptoms since several years. PMID- 7981170 TI - Fractures about the knee: growth disturbances and problems of stability at long term follow-up. AB - The aim of this study was to collect information about the incidence of leg length discrepancy, axis deviation and instability resulting from fractures about the knee in childhood. We reviewed 43 patients with a clinical and radiological examination after a mean follow-up period of 13 years. The fractures were divided into four subgroups, each one presenting typical problems. Growth disturbance (shortening and axis deviation) making secondary procedures necessary was seen in 5 out of 14 (36%) distal femoral epiphyseal fractures. Complex instability was observed in 3 out of 7 (43%) proximal tibial epiphyseal fractures. In the tibial spine fractures anatomical reduction often did not prevent moderate cruciate ligament insufficiency; and in the metaphyseal fractures 2 of the 7 cases showed leg-lenghtening. In conclusion, the Salter classification seems to be of little prognostic value at the knee as Type-II fractures are frequently followed by asymmetric growth arrest. Open reduction is not reliable in avoiding this complication. Associated ligament injuries are not rare and deserve more attention. PMID- 7981171 TI - Interference with the function of leukocyte adhesion molecules by monoclonal antibodies: a new approach to burn injury. AB - Monoclonal antibody to intercellular adherence molecule-1 (ICAM-1) was used to inhibit leukocyte adherence in two models of burn injury. The antibodies to ICAM 1 had significant effects in preserving microvascular blood flow in burn wounds, and in modulating the systemic response to major burn injury. These results suggest a central role for leukocytes in the pathophysiologic response to burn injury. PMID- 7981172 TI - Alteration of the immune system in burns and implications for therapy. AB - Following thermal injury profound alterations occur in the arachidonic acid cascade, and the cytokine cascade. There are further alterations in cell mediated immunity affecting all cells of the immune system, and the neuro endocrine axis. There are profound changes in humoral immunity as well. Experimental approaches to alterations in the above systems indicate that success can be obtained in restoring normality of any individual alteration in a suitable experimental model. However, before clinical intervention can be successful, it is likely that a combination of interventional mordalities will need to be used. PMID- 7981173 TI - Multiple organ dysfunction syndrome (MODS) following multiple trauma: rationale and concept of therapeutic approach. AB - The multiple organ dysfunction syndrome (MODS) represents the number one cause of death in surgical intensive care units. It is divided into a primary and a secondary MODS based on time of manifestation and pathophysiologic events which attribute to it. The therapy of the primary MODS includes sufficient and quick resuscitation, adequate oxygen delivery and early enteral nutrition to reduce or avoid the incidence of bacterial translocation. In addition, a reduction of the "antigenic load" by control of hemorrhage, radical wound debridement, decompression, and fixation of long bone fractures appears to be effective in reducing the occurrence of MODS. The treatment of the secondary MODS remains supportive and its prevention is essential. Further studies are necessary to evaluate the clinical significance of new therapeutic agents such as monoclonal antibodies or cytokine receptor antagonists. PMID- 7981174 TI - Transplantation of fetal adrenal glands in syngeneic rat strains. AB - In a syngeneic rat model we investigated the feasibility of fetal adrenal gland transplantation into adult recipient animals. We determined the optimal site of graft implantation by morphological criteria. Transplantation into the omentum majus proved superior to transplantation underneath the fascia of the rectus abdominis muscle possibly due to superior access to vascular supply. We assessed transplant function by sequential determinations of serum corticosterone, aldosterone, sodium and body weight. We compared rats which received syngeneic fetal adrenal transplants and underwent excision of their own adrenal glands four weeks thereafter to control animals without adrenalectomy or transplantation and to adrenalectomized animals without prior transplantation. The total study period was 16 weeks. Whereas all adrenalectomized rats without prior transplantation died within 2 weeks, all the animals which had received fetal adrenal grafts survived. Their serum sodium remained within normal limits. Weight gain and serum corticosterone levels were decreased when compared to control animals. Aldosterone levels dropped intermittently but had normalized by 16 weeks. We conclude that fetal adrenal grafts may be able to substitute for the animals' own adrenal glands in the syngeneic model. PMID- 7981175 TI - Common carotid intima-media thickness and lower extremity arterial atherosclerosis. The Rotterdam Study. AB - High-resolution B-mode ultrasonography of the carotid arteries is used to investigate the signs of early atherosclerotic vessel wall disease. To assess whether carotid artery findings reflect atherosclerosis elsewhere, we studied the association between common carotid intima-media thickness and lower extremity arterial atherosclerosis among the first 1000 participants of the Rotterdam Study. The Rotterdam Study is a single-center population-based prospective follow up study of 7983 subjects, > or = 55 years old. Baseline measurements include ultrasound imaging of intima-media thickness of the distal common carotid artery and determination of the ankle-to-arm systolic blood pressure index. Lower extremity arterial disease was defined as an ankle-arm index < 0.90 in at least one leg. An increase of 0.1 mm in common carotid artery intima-media thickness was associated with an age- and sex-adjusted reduction of the ankle-arm index of 0.026 (95% confidence interval [CI]: 0.018 to 0.034). The age- and sex-adjusted odds ratio of lower extremity arterial disease for subjects with an intima-media thickness > or = 0.89 mm (upper quintile) to that of subjects with an intima media thickness < 0.89 mm was 3.4 (95% CI: 2.2 to 5.2). Analysis among subjects free from symptomatic cardiovascular disease yielded a reduction in ankle-arm index per 0.1 mm increase in intima-media thickness of 0.018 (95% CI: 0.008 to 0.28) and an odds ratio for lower extremity arterial disease of 3.0 (95% CI: 1.7 to 5.1). Adjustments for differences in serum lipids, hypertension, and current smoking status only slightly attenuated the results.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7981176 TI - LDL oxidation in patients with severe carotid atherosclerosis. A study of in vitro and in vivo oxidation markers. AB - Among the various risk factors involved in the development and progression of carotid atherosclerosis, the oxidation of LDL has been proposed to play a relevant role. LDL oxidation has been investigated in 94 patients with severe carotid atherosclerosis undergoing elective carotid artery endarterectomy and in 42 matched control subjects. LDL oxidation was evaluated in all patients as (1) the susceptibility to in vitro oxidation, (2) vitamin E concentration and its efficiency in LDL, and (3) the presence of autoantibodies against oxidatively modified lipoprotein to monitor the occurrence of the oxidative processes taking place in vivo. No difference was detected between control subjects and patients concerning vitamin E concentration and the kinetics of conjugated diene formation in isolated LDL exposed to CuSO4. However, vitamin E efficiency was lower (9.6 +/ 4.2 versus 30.2 +/- 7.6 min/nmol vitamin E) and the duration of the vitamin E independent lag phase was longer (105.5 +/- 16.5 versus 58 +/- 11.8 minutes) in the patient group. Autoantibodies against oxidatively modified lipoproteins were measured with an ELISA method using native LDL, Cu(2+)-oxidized LDL (oxLDL), or malondialdehyde-derivatized LDL (MDA-LDL) as antigens. To monitor cross reactivity of the antibodies detected with other oxidatively modified proteins, human serum albumin (HSA) and MDA-derivatized HSA (MDA-HSA) were also employed. The antibody titer was calculated as the ratio of antibodies against modified versus native proteins.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7981177 TI - Oxidized lipids in the diet are a source of oxidized lipid in chylomicrons of human serum. AB - We examined whether oxidized lipids in the diet determine the levels of oxidized lipid in human postprandial serum chylomicrons. After we fed subjects control corn oil containing low quantities of oxidized lipid, the levels of conjugated dienes in the chylomicron fraction were low (9.67 +/- 0.92 nmol/mumol triglyceride), and no thiobarbituric acid-reactive substances (TBARS) could be detected. However, when subjects were fed a highly oxidized oil, the conjugated diene content in chylomicrons was increased 4.7-fold to 46 +/- 5.63 nmol/mumol triglyceride, with 0.140 +/- 0.03 nmol TBARS/mumol triglyceride. When subjects were fed medium-oxidized oil, the degree of oxidation of the chylomicron lipids was moderately increased (21.86 +/- 2.03 nmol conjugated dienes/mumol triglyceride). Additionally, we found that chylomicrons isolated after ingestion of oxidized oil were more susceptible to CuSO4 oxidation than chylomicrons isolated after ingestion of the control oil. The lag time for oxidation decreased from 4.30 +/- 0.40 to 3.24 +/- 0.51 hours (P < .05). These data demonstrate that in humans dietary oxidized lipids are absorbed by the small intestine, incorporated into chylomicrons, and appear in the bloodstream, where they contribute to the total body pool of oxidized lipid. PMID- 7981178 TI - Effects of lovastatin on ApoA- and ApoB-containing lipoproteins. Families in a subpopulation of patients participating in the Monitored Atherosclerosis Regression Study (MARS). AB - To establish whether lovastatin, an inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase, exhibits a specific effect on apolipoprotein (apo) A- and apoB-containing lipoproteins, 63 subjects, a subset of the 270 Monitored Atherosclerosis Regression Study (MARS) patients with hypercholesterolemia (190 to 295 mg/dL) and documented coronary artery disease, were randomized into either lovastatin 40 mg twice daily or matching placebo tablets twice daily. Both groups consumed a diet containing 27% calories as fat (polyunsaturated fat/saturated fat ratio, 2.85) and a daily cholesterol intake of less than 250 mg. The plasma lipid and apolipoprotein profiles were determined at the time of randomization and after 2 years of treatment, and the levels of apoA- and apoB-containing lipoprotein families were measured after 2 years of treatment. After this treatment period, the drug group was characterized in comparison with the placebo group by significantly reduced levels of total cholesterol (33%), triglycerides (30%), very-low-density lipoprotein cholesterol (36%), low-density lipoprotein cholesterol (43%), apoB (36%), apoC-III (18%), and apoE (17%) and slightly but insignificantly increased levels of high-density lipoprotein cholesterol (6%) and apoA-I (1%). The 2-year levels of lipoprotein containing apoA-I but no apoA-II (LpA-I) and lipoprotein containing both apoA-I and apoA-II (LpA-I/A-II) particles separated by immunoaffinity chromatography on an anti-apoA-II immunosorber did not differ between the two treatment groups. However, the apoB-containing lipoprotein (Lp) families defined by apolipoprotein composition and separated by immunoaffinity chromatography on anti-apoA-II and anti-apoC-III immunosorbers were affected in a selective manner.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7981179 TI - A nonsense mutation in the apolipoprotein A-I gene is associated with high density lipoprotein deficiency and periorbital xanthelasmas. AB - Conflicting data from epidemiological trials, genetic family studies, transgenic animal models, and in vitro experiments have created controversy regarding the importance of HDL and apolipoprotein (apo) A-I for reverse cholesterol transport and protection from atherosclerosis. In this study we identified a homozygous nonsense mutation in codon 32 (Q32X) of the apoA-I gene as the molecular basis of apoA-I deficiency in a 31-year-old woman who did not present with clinical signs of atherosclerosis. Despite half-normal plasma concentrations of HDL cholesterol and apoA-I in subjects heterozygous for this mutation, the history of the patient's large family did not indicate any increased prevalence of myocardial infarction. PMID- 7981180 TI - Association of factor VII genotype with plasma factor VII activity and antigen levels in healthy Indian adults and interaction with triglycerides. AB - Plasma factor VII activity (factor VIIc) is one of the independent risk factors for coronary artery disease and is controlled by both genetic and environmental factors. Several studies in healthy Caucasian subjects have revealed an association of a common genetic polymorphism at residue 353 (Arg-->Gln) of the factor VII gene with plasma factor VIIc. We have investigated the influence of this polymorphism (factor VII Arg/Gln353) on fasting plasma factor VIIc and antigen (factor VIIag) levels and its interaction with triglyceride levels in 185 healthy Dravidian Indians of both sexes (128 men, 57 women). The frequency of Gln353 has been found to be significantly higher in Dravidian Indians (0.29; confidence interval, 0.27 to 0.30) than in Caucasians (0.10). The distribution of factor VII Arg/Gln353 genotypes was at Hardy-Weinberg equilibrium. The carriers of the Gln353 allele had significantly lower plasma factor VIIc and factor VIIag in men (P < .05). The factor VII Arg/Gln353 polymorphism explained 13% and 11% of the total variance of plasma factor VIIc and factor VIIag, respectively, in men (P < .001) and 6% and 9% in women (P > .1). The genotype-specific correlation of factor VIIc and factor VIIag with triglyceride levels was stronger in carriers of the Gln353 allele (r = .38 and .41; P < .001) than in Arg353 homozygotes (r = .09 and .27; P = .19 and .005, respectively). PMID- 7981181 TI - Intraindividual variability of fibrinogen levels and cardiovascular risk profile. AB - Prospective population studies have established that fibrinogen is an independent predictor for ischemic heart disease and stroke. These study conclusions have prompted recommendations that fibrinogen determinations be included in the cardiovascular risk profile. The routine availability of fibrinogen measurements may result in widespread screening prior to establishing the validity of a single fibrinogen level as an accurate descriptor for individual subjects. The objectives of this study were to describe the methodological and intraindividual components of variability in fibrinogen measurements determined by using the Clauss method; to establish the usefulness of a single fibrinogen measurement on risk stratification and retest reproducibility; and to determine the influence of intraindividual fibrinogen variability on sample size estimates. Fibrinogen levels were measured by a modification of the Clauss method. Three cohorts of apparently healthy, nonsmoking volunteers were recruited. The single-day intra individual component of fibrinogen variability was determined in 39 subjects. For the 5-day intraindividual component of fibrinogen variability, 32 subjects were recruited, and in the 6-week intraindividual study, 28 subjects were included. The coefficient of variation for the methodological component of fibrinogen variability was 5.8% as determined from batch analyses, but the intraindividual coefficient of variation for replicate measures on a single day was 10.7%. The 5 day intraindividual coefficient of variation was 14.2%, and for the 6-week period it was 17.8%. Based on the 6-week data, an average of four fibrinogen measures is required to reduce misclassification error to less than 10%. Sample size estimates were made based on predetermined levels of statistical power and the 6 week intraindividual and interindividual variability estimates.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7981182 TI - Intraperitoneal insulin therapy corrects abnormalities in cholesteryl ester transfer and lipoprotein lipase activities in insulin-dependent diabetes mellitus. AB - Patients with insulin-dependent diabetes mellitus (IDDM) have proatherogenic disturbances in cholesteryl ester transfer (CET) despite intensive subcutaneous insulin therapy (ISC). Since CET is activated by insulin-sensitive lipoprotein lipase (LPL), which normally increases postprandially, we queried whether iatrogenic hyperinsulinism from ISC stimulated LPL and CET by studying well controlled IDDM patients after ISC and then 6 months after lowering systemic insulin levels by intraperitoneal (IP) insulin delivery. Although glycemic control (HbA1c IDDM, 6.9 +/- 1.7%; control, 4.5% to 8%) was excellent during ISC, CET was accelerated (P < .001) and both systemic insulin levels and LPL specific activity were increased (P < .05). Following IP, basal systemic insulin levels declined by more than one half (ISC, 8.22 +/- 6.5 versus IP, 2.77 +/- 2.4 microU/mL; mean +/- SD; P < .025), and both LPL and CET activities returned to normal. Plasma triglyceride, cholesterol, high-density lipoprotein-2 (HDL2) cholesterol, HDL3 cholesterol, cholesteryl ester transfer protein mass, and glycemic control (HbA1c, 6.3 +/- 0.8%) were unchanged and remained normal. These findings indicate that ISC is associated with high levels of basal CET and LPL. These alterations both appear to be closely linked to iatrogenic hyperinsulinemia resulting from ISC. The fact that they are both reversed when systemic insulin levels are reduced by IP suggests that insulin, acting through LPL, influences the nature of the interaction of the lipoproteins engaged in CET.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7981184 TI - The insulin resistance syndrome in smokers is related to smoking habits. AB - The relationship between smoking habits, insulin resistance, and related risk factors for cardiovascular disease was examined in 57 middle-aged male smokers whose degree of insulin resistance was quantified by using the euglycemic clamp technique. Smoking habits correlated with degree of insulin resistance and consequently with various manifestations of the insulin resistance syndrome including levels of insulin, high-density lipoprotein cholesterol, triglycerides, and plasminogen activator inhibitor-1 (PAI-1) activity. Smoking habits, independent of degree of insulin resistance, were also related to levels of total cholesterol and low-density lipoprotein cholesterol as well as triglycerides. Stepwise regression analyses considering the effects of age, lean body mass, body fat, body mass index, waist/hip ratio, and alcohol consumption showed that only smoking habits and percent body fat were independently related to degree of insulin resistance. This study shows that insulin resistance and the insulin resistance syndrome are important but not unique contributors to the strong risk profile for cardiovascular disease in middle-aged men who smoke. PMID- 7981183 TI - Multivariate analysis of the insulin resistance syndrome in women. AB - The insulin resistance syndrome (IRS) is characterized by a constellation of interrelated coronary heart disease (CHD) risk factors, including dyslipidemia, obesity, central obesity, elevated systolic blood pressure, and hyperinsulinemia. Factor analysis was used to investigate the clustering of these risk factors in individuals by examining the correlational structure among these variables. Data from 281 genetically unrelated nondiabetic women who participated in exam 2 (1979 to 1980) of the Kaiser Permanente Women Twins Study were used. Factor analysis reduced 10 correlated risk factors to 3 uncorrelated factors, each reflecting a different aspect of the IRS: factor 1 (increased body weight, waist circumference, fasting insulin, and glucose), factor 2 (increased postload and fasting glucose and insulin and systolic blood pressure), and factor 3 (larger low-density lipoprotein particles, decreased plasma triglycerides, and increased high-density lipoprotein). Together, the factors explained nearly 66% of the total variance in the data. Thus, factor analysis defined three distinct aspects of the IRS in this sample of nondiabetic women. These factors may reflect separate underlying mechanisms of the syndrome, each of which may also be involved in CHD risk. PMID- 7981185 TI - 13C-NMR spectroscopy of human atherosclerotic lesions. Relation between fatty acid saturation, cholesteryl ester content, and luminal obstruction. AB - Previous investigations have used 13C-nuclear magnetic resonance (NMR) spectroscopy to demonstrate the similarities between lipoproteins and the mobile lipids of atheroma. In this study, we tested the hypothesis that 13C-NMR changes are related to indices of histological severity. We classified 20 human arteries according to their obstruction ratio (OR), defined as the ratio of the plaque area to the area delimited by the external elastic lamina. In group A, OR was < 40%, and in group B, OR was > 40%. We analyzed at 9.4 T the resonances of unsaturated (UFA) and polyunsaturated (PUFA) carbons, the resonances of the carbons 19 and 21 (C19, C21) of cholesteryl esters (CE), the methine carbon peak of fatty acids (CH2)n, the choline peak from phospholipids (PL), and the glycerol peak from triglyceride (TG). The UFA/PUFA, UFA/(CH2)n, and PUFA/(CH2)n ratios are markers of fatty acid saturation. (C19, C21)/(CH2)n, choline/(CH2)n, and glycerol/(CH2)n are indices of CE, PL, and TG content, respectively. UFA/PUFA in group A is 1.15 +/- 0.34 versus 1.63 +/- 0.32 in group B (P = .005). PUFA/(CH2)n is 0.26 +/- 0.10 in group A versus 0.16 +/- 0.04 in group B (P = .049). C19, C21/(CH2)n in group A is 0.32 +/- 0.15 versus 0.63 +/- 0.23 for group B (P = .003). No significant difference was found in UFA/(CH2)n or in the TG or PL ratios. 13C spectral examination of human atherosclerosis demonstrates decreased resonances for polyunsaturated fatty acyl chains and cholesteryl esters with increasing obstruction. PMID- 7981186 TI - Three novel mutations of antithrombin inducing high-molecular-mass compounds. AB - We have identified three novel mutations of the antithrombin (AT) gene in patients with thrombotic complications: a Cys 128 --> Tyr mutations, a G --> A mutation in the intervening sequence 4 (IVS4) 14 nucleotide 5' to exon 5, and a 9 bp deletion in the 3' end of exon 6 resulting in a short aberrant sequence after Arg 425. The latter mutation was associated with an Arg 47 --> His mutation in two compound heterozygous brothers. These three mutations led to the expression in the circulation of small amounts of inactive molecules with a high molecular mass in immunoblot analysis. In reducing conditions, these variant molecules had a normal molecular mass, which led us to postulate that these mutations prevent the formation of one intramolecular disulfide bond and allow the formation of intermolecular disulfide bonds. Plasma from a heterozygous patients bearing the Cys 128 --> Tyr mutation and from a compound heterozygote bearing the Arg 47 --> His mutation and the 9 bp deletion in exon 6 were passed through a heparin sepharose column. In both cases a population of high-molecular-weight AT molecules with no binding affinity and no AT activity was separated from a population of normal molecules in the first patient, together with a population of molecules with a reduced binding affinity for heparin due to the substitution of Arg 47, in the compound heterozygote. The common feature of these three mutations is that they lead to partial misfolding and to the formation of intermolecular disulfide bonds with other plasma components, inducing the pleiotropic phenotypes observed. PMID- 7981187 TI - Oxidation of heparin-isolated LDL by hemin. The effect of serum components. AB - Oxidation of low-density lipoprotein (LDL) in the artery wall is probably determined by several factors, some of which may include physiological oxidants such as heme and hydrogen peroxide, blood serum components, and the interaction of the lipoprotein with glycosaminoglycans. Glycosaminoglycans form complexes with LDL that increase its susceptibility to oxidation in vitro. To examine the effect of these factors on oxidation of LDL from serum by using heparin and oxidized the resolubilized lipoprotein (Hep-LDL) with hemin and hydrogen peroxide in the presence of apolipoprotein B lipoprotein-deficient serum (BLPDS). Low levels (2.1%) of BLPDS stimulated the oxidation of Hep-LDL by approximately fivefold, and increasing concentrations reduced oxidation to baseline rates. By comparison, the oxidation of native LDL was stimulated to a similar extent at lower concentrations of BLPDS (0.83%) and returned to baseline more rapidly with increasing levels of the serum fraction. Oxidation rates did not change significantly with increasing concentrations of BLPDS alone. Human serum albumin (HSA) at comparable levels produced changes in the oxidation of Hep-LDL similar to those seen with BLPDS. Degradation of heme was accelerated by low levels of BLPDS or HSA in the presence of hydrogen peroxide but not by higher levels, and maximal degradation rates were inhibited by comparatively low levels of butylated hydroxytoluene (35 mumol/L). This antioxidant also effectively inhibited oxidation of Hep-LDL maximally stimulated by BLPDS. The data suggest that serum components, particularly HSA, modulate the peroxidation of both glycosaminoglycan treated LDL and native LDL by hemin and hydrogen peroxide via mechanisms that may involve oxidative interactions between heme and HSA. This phenomenon may influence oxidation of LDL in vivo, where levels of HSA in regions of the artery wall are comparable with levels that stimulate the oxidation of Hep-LDL in vitro. PMID- 7981189 TI - A perfusion chamber developed to investigate thrombus formation and shear profiles in flowing native human blood at the apex of well-defined stenoses. AB - The precipitating event leading to stroke, myocardial infarction, and/or sudden death may be related to the formation of mural thrombus at the site of a ruptured or superficially damaged stenotic plaque. The fluid dynamic properties at atherosclerotic plaques that may be implicated in this thrombus formation have been described in a wide variety of model systems in both the process of plaque rupture and the growth of platelet thrombi. In general, the local fluid dynamic conditions are complex and show major variations from flow in well-defined laminar flow systems. However, no studies have attempted to quantify the effect of stenosis-related disturbances on thrombus formation in native human blood and to compare them with the local fluid dynamics. We developed a parallel-plate perfusion chamber device in which thrombus formation is measured at the "apex" of eccentric stenoses and have correlated such measurements with values of the local fluid dynamics obtained by computer simulation. The extent of stenoses (reduction in the cross-sectional area of the blood flow channel) was 60%, 80%, and 89%, corresponding to "apex" wall shear rates of 2600, 10,500, and 32,000 sec-1, respectively. The wall shear rate in the laminar flow region proximal and distal to the stenoses was 420 sec-1. The surface of the stenosis was purified collagen type III fibrils that were exposed to flowing nonanticoagulated human blood drawn directly from an antecubital vein by a pump placed distally to the perfusion chamber. The resulting blood-collagen interactions were quantified by light microscopy by using a morphometric image analysis technique. Under all conditions studied, platelet thrombus formation at the "apex" was extensive.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7981188 TI - Tissue factor-induced coagulation triggers platelet thrombus formation as efficiently as fibrillar collagen at arterial blood flow conditions. AB - The relative importance of vessel wall tissue factor (TF) in initiating thrombogenesis is not well defined. In contrast, vessel wall collagens have been well documented as potent inducers of thrombus formation. We compared the potency of a human TF/phospholipid surface with that of a surface consisting of human type III collagen fibrils in triggering thrombus formation in native human blood at venous and arterial blood flow conditions. A commercial preparation, Thromborel S, was used as a source of human TF. Biochemical characterization of this preparation revealed small amounts of FVII, FIX, and FX proteins. Coagulant activity of these proteins was associated with the FVII protein only, although it was a very low activity. Studies with anti-TF antibodies in a one-stage clotting assay showed that the procoagulant activity of Thromborel was mainly a result of TF. The molar ratio of TF to phospholipid was 1:2 x 10(7). Thrombus formation in flowing nonanticoagulated human blood drawn directly from an antecubital vein was triggered by either Thromborel S or collagen fibrils coated on Thermanox coverslips in a parallel-plate perfusion chamber device. A 1:50 Thromborel S dilution gave maximal fibrin deposition (90% surface coverage) at a wall shear rate of 100 s-1. However, pretreatment of the TF surface with a monoclonal anti TF antibody reduced this fibrin deposition by 93% (P < .001). Thus, TF was essential for the procoagulant activity of the Thromborel S surface in this flow system also. At higher wall shear rates (650 and 2600s-1), less fibrin was deposited, but the platelet thrombus formation on the fibrin mesh increased dramatically.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7981190 TI - Antiproliferative activity to vascular smooth muscle cells and receptor binding of heparin-mimicking polyaromatic anionic compounds. AB - Proliferation of bovine aortic smooth muscle cells (SMCs) induced by thrombin, basic fibroblast growth factor, or serum is inhibited by anionic, nonsulfated aromatic compounds that mimic many of the effects of heparin. Among these compounds are aurintricarboxylic acid (ATA) and a newly synthesized polymer of 4 hydroxyphenoxy acetic acid (compound RG-13577). Iodinated- or 14C-labeled compound RG-13577 binds to cultured SMCs in a highly specific and saturable manner. Scatchard analysis of the binding data revealed the presence of an estimated 1 x 10(7) binding sites per cell with an apparent dissociation constant of 3 x 10(-6) mol/L. Binding of radiolabeled RG-13577 was efficiently competed for by related aromatic anionic compounds and by apolipoprotein E, but not by heparin, heparan sulfate, suramin, or various purified growth factors and extracellular matrix proteins. Receptor cross-linking of SMC-bound 125I-RG-13577 revealed a single species of high M(r) (approximately 280 kD) cell surface receptors detected in the absence but not the presence of excess unlabeled compound RG-13577. Binding was susceptible to downregulation and restoration of receptor levels in a manner similar to that of hormone and growth factor receptors. We suggest that the antiproliferative activity of compound RG-13577 and related compounds is initiated by binding to specific growth-inhibiting cell surface receptors. Heparin-mimicking compounds may be applied to inhibit SMC proliferation associated with atherosclerosis and restenosis. PMID- 7981191 TI - Mechanically induced calcium mobilization in cultured endothelial cells is dependent on actin and phospholipase. AB - We sought to evaluate the mechanisms by which mechanical perturbation elevates intracellular calcium in endothelial cells. We report that the transient elevation in intracellular calcium in cultured bovine aortic endothelial cells (BAEC) in response to gentle perturbation with the side of a micropipette was not blocked by depolarization (external K+, 130 mmol/L), nifedipine (10 mumol/L), or Bay K 8644 R(+) (10 mumol/L). Thus, voltage-dependent calcium channels were not involved in the response. Also, amiloride (10 mumol/L) and tetraethylammonium (1 mmol/L) had no effect on calcium mobilization, indicating that Na+ and K+ transporters were not involved. Pretreatment of the cells with the phospholipase C and phospholipase A2 inhibitor manoalide (10 mumol/L) for 10 minutes at 37 degrees C completely abolished the calcium response, as did a 10-minute pretreatment with the inhibitor of actin polymerization, cytochalasin B (1 mumol/L). We observed an inhibitory effect of the phospholipase A2 and phospholipase C inhibitor 4-bromophenacyl bromide (10 mumol/L) on the mechanical response of BAEC that was not as potent as that observed with manoalide. To examine the role of arachidonic acid (AA) and subsequent metabolites that may be released after a putatively mechanical activation of phospholipase A2, we exposed BAEC to exogenous AA. We found that continued exposure of BAEC for 5 minutes to 10 nmol/L to 10 mumol/L AA caused no elevation of intracellular calcium. If mechanical stimulation activates phospholipase A2, the liberated AA and subsequent metabolites do not appear to have much effect on BAEC intracellular calcium.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7981193 TI - Hyperlipidemia accelerates allograft arteriosclerosis (chronic rejection) in the rat. AB - The relevance of hyperlipidemia in allograft arteriosclerosis (chronic rejection) is controversial. Isolated hypercholesterolemia induced with cholesterol-cholic acid-diet (CC-diet) or hypertriglyceridemia induced with glycerol-diet (G-diet) had no or only a protective effect on aortic allograft arteriosclerosis in the rat. Combined hyperlipidemia with both diets (CC+G-diet) enhanced allograft arteriosclerosis by doubling intimal thickness and cellularity (P < .05) but had no effect on host arteries. Compared with normolipidemic controls, the CC+G-diet increased the total serum cholesterol concentration 4.8-fold (P < .05). Levels of VLDL2 and IDL increased 4.8- and 18.1-fold (P < .05), and their composition changed from triglyceride-rich to cholesterol-rich lipoproteins in an atherogenic direction. The CC+G-diet had no effect on the structure of inflammation in the vascular wall. Instead, significant lipid deposits were observed, and the expression of epidermal growth factor and insulin-like growth factor-1 was significantly elevated in the vascular wall. Thus, elevations in VLDL and IDL lipoprotein levels and their cholesterol content associate with the generation of allograft arteriosclerosis in rats. Deposition of lipids in the vascular wall seems to induce local synthesis of certain growth factors, which ultimately leads to the induction of smooth muscle cell replication. PMID- 7981192 TI - Long-term induction and regression of diet-induced atherosclerotic lesions in rhesus monkeys. II. Morphometric evaluation of lesions by light microscopy in coronary and carotid arteries. AB - Atherosclerotic lesions were induced in rhesus monkeys (Macaca mulatta) by feeding them a high-saturated fatty acid and high-cholesterol diet. After 5.4 years the extent of lesions in three major coronary arteries and the right carotid artery was evaluated morphometrically by light microscopy in one group of animals (group P). The remaining animals were switched to a low-cholesterol diet that remained high in saturated fatty acids and provided the same percentage of total calories as did the atherogenic diet. Lesion regression was then evaluated in one group of monkeys 1.9 years (group R4) and in another group of monkeys 3.7 years (group R5) after withdrawal of cholesterol alone from the diet. In group P, the mean intimal thickness varied between 26 and 47 microns, maximum intimal thickness between 70 and 92 microns, and luminal reduction between 9% and 12% in the three major coronary arteries. Luminal reduction varied between 1% and 11% in right carotid artery segments. After 1.9 years of consuming the basal diet, group R4 animals were no different from group P animals with respect to morphometric measures. Total intimal and medial areas of the left anterior descending (LAD) coronary artery in groups P and R4 were also similar. In contrast, after 3.7 years of consuming the basal diet, group R5 animals showed consistently although not statistically significantly lower values than those in group P for the morphometric measures in coronary arteries and total intimal area in the LAD. Similar results were obtained for the common carotid and external carotid arteries. Thus, our study shows that long-term diet-induced lesions in coronary arteries and in common and external segments of the right carotid artery regressed only when the animals were fed the basal diet for 3.7 years. We conclude that atherosclerotic lesions induced in coronary and carotid arteries can regress toward normal to a certain extent, but they require a longer time for regression than do other arterial segments. These findings support the results of clinical trials in human subjects. PMID- 7981194 TI - Cytomegalovirus infection enhances mRNA expression of platelet-derived growth factor-BB and transforming growth factor-beta 1 in rat aortic allografts. Possible mechanism for cytomegalovirus-enhanced graft arteriosclerosis. AB - We have recently demonstrated that rat cytomegalovirus (RCMV) infection induces an early inflammatory response in the adventitia (perivasculitis) and in the subendothelial space (endothelialitis) as well as doubles smooth muscle cell (SMC) proliferation and intimal thickening of rat aortic allografts performed from the DA (AG-B4, RT1a) to the WF (AG-B2, RT1v) strain. In this study, the impact of RCMV infection on the structure of inflammation in the allograft adventitia and on the expression of SMC growth factors in the allograft vascular wall was investigated. The recipient rats were inoculated with 10(5) plaque forming U of RCMV Maastricht strain or left noninfected and used as controls. The allografts were removed at 7 days and 1 and 3 months after transplantation and processed for morphometry and immunohistochemistry. RNA was isolated for reverse transcriptase polymerase chain reaction (RT-PCR). RCMV infection was associated with significantly upregulated presence (P < .05) of T helper (W3/25), T cytotoxic (OX8), and natural killer (3.2.3) cells in the allograft adventitia 7 days after transplantation but not thereafter. More monocyte/macrophages (OX42) were also present in RCMV-infected allografts, but the difference was not significant. Concomitantly, RCMV infection significantly enhanced (P < .05) the expression of major histocompatibility complex class II (OX6) and almost doubled (P = NS) the expression of interleukin-2R (CD25), intercellular adhesion molecule 1 (CD54;1A29), and lymphocyte function-associated antigen-1 alpha-chain (CD11a; WT.1) in the adventitial inflammatory infiltrate. RCMV infection was linked with an early, prominent expression of both PDGF-BB mRNA at 7 days (P < .05) and at 1 month (P < .025) and of transforming growth factor-beta 1 mRNA at 7 days (P < .025) and at 1 month (P < .025) after transplantation. A less-prominent mRNA upregulation of acidic fibroblast growth factor (P < .05) was associated with RCMV infection at 7 days and at 1 month, as well as of epidermal growth factor at 1 month after transplantation, when compared with noninfected allografts, although the mRNA expression in both groups was below the levels of nontransplanted DA aortas. RCMV infection almost doubled basic fibroblast growth factor mRNA expression (P = NS) in the allograft vascular wall at 7 days and at 1 month. RCMV infection had no additional impact on insulin-like growth factor-1 mRNA expression when compared with noninfected allografts.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 7981195 TI - Hypercatabolism of lipoprotein-free apolipoprotein A-I in HDL-deficient mutant chickens. AB - The Wisconsin Hypoalpha Mutant (WHAM) chicken has a sex-linked mutation associated with a 90% reduction in high-density lipoprotein (HDL) cholesterol and apolipoprotein A-I (apoA-I). In the present studies, we did not detect a defect in apoA-I synthesis or secretion in liver or intestine. We tested the hypothesis that apoA-I is not binding properly to lipoprotein particles and is undergoing hypercatabolism. We therefore studied the in vivo turnover of lipid-free 125I apoA-I. Its turnover was fourfold faster in WHAM chickens than in normal chickens. The 125I-apoA-I equilibrated more slowly with HDL in the WHAM chickens, and these animals had a much larger steady-state pool of lipid-free apoA-I than did control chickens. To determine the tissue sites of degradation of apoA- I, the tissue distribution of 125I-tyramine cellobiose apoA-I was assessed. The liver and kidneys were the major sites of apoA-I degradation, but in the WHAM chickens, the kidney made a twofold larger contribution to apoA-I degradation than in normal chickens. Total plasma phospholipid levels are reduced by 44% to 78% in the WHAM chickens. A phospholipid deficit might explain the elevated lipid free apoA-I pool and, secondarily, the HDL deficiency of the WHAM chickens. PMID- 7981196 TI - Complete chemical structure of photoactive yellow protein: novel thioester-linked 4-hydroxycinnamyl chromophore and photocycle chemistry. AB - The unique ability of photoactive proteins to capture and use energy from a photon of light depends on the chromophore, its linkage to the protein, and the surrounding protein environment. To understand the molecular mechanisms by which a chromophore and protein interact to undergo a light cycle, we are studying photoactive yellow protein (PYP), a 14-kDa water-soluble photoreceptor from Ectothiorhodospira halophila with a photocycle similar to that of sensory rhodopsin. Here, we report the cloning and sequencing of the pyp gene and the chemical identification of both the chromophore and its covalent linkage to the protein. Elemental composition data from high-resolution mass spectrometry of a proteolytically derived chromopeptide, pH titrations and UV-visible spectroscopy of the protein-bound and chemically released chromophore, and fragmentation mass spectrometry of the liberated chromophore amide were combined with results from the 1.4-A-resolution protein crystal structure to identify the chromophore in PYP as a 4-hydroxycinnamyl group covalently bound to the sole cysteine residue via a thioester linkage. While 4-hydroxycinnamate is a metabolic product of the phenylpropanoid pathway and a key molecule in plant stress response, this is the first report of covalent modification of a protein by this group. In the dark (yellow) state of PYP, the protein stabilizes the chromophore as the deprotonated phenolate anion. By combining our biochemical characterization of the chromophore with other published observations, we propose a chemical basis for the photocycle: following the initial absorption of a photon, the photocycle of PYP involves protonation of the chromophore to a neutral phenol form corresponding to the observed photobleached intermediate. PMID- 7981197 TI - Binding sites of quinones in photosynthetic bacterial reaction centers investigated by light-induced FTIR difference spectroscopy: assignment of the interactions of each carbonyl of QA in Rhodobacter sphaeroides using site specific 13C-labeled ubiquinone. AB - Light-induced QA-/QA FTIR difference spectra of the photoreduction of the primary quinone (QA) have been obtained for Rhodobacter sphaeroides reaction centers (RCs) reconstituted with ubiquinone (Q3) labeled selectively with 13C at the 1- or 4-position of the quinone ring, i.e., on either of the two carbonyls. The vibrational modes of the quinone in the QA site are compared to those in vitro. IR absorption spectra of films of the labeled quinones show that the two carbonyls contribute equally to the split C = O band at 1663-1650 cm-1. This splitting is assigned to the two different geometries of the methoxy group nearest to each carbonyl. The QA-/QA spectra of RCs reconstituted with either 13C1- or 13C4-labeled Q3 and with unlabeled Q3 as well as the double differences calculated from these spectra exhibit distinct isotopic shifts for the bands assigned to C = O and C = C vibrations of the neutral QA. For the unlabeled QA, these bands correspond to the bands at 1660, 1628, and 1601 cm-1 previously detected upon nonselective isotopic labeling [Breton, J., Burie, J.-R., Berthomieu, C., Berger, G., & Nabedryk, E. (1994) Biochemistry 33, 4953-4965]. The 1660-cm-1 band is unaffected upon selective labeling at C4 but shifts to approximately 1623 cm-1 upon 13C1 labeling, demonstrating that this band arises from the C1 carbonyl, proximal to the isoprenoid chain. The band at 1628 cm-1 shifts by 11 and 16 cm-1 upon 13C1 and 13C4 labeling, respectively, and is assigned to a C = C mode coupled to both carbonyls.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7981198 TI - Transient kinetic analysis of rhodamine phalloidin binding to actin filaments. AB - We have characterized the binding of rhodamine phalloidin to actin filaments and actin filaments saturated with either myosin subfragment-1 or tropomyosin in 50 mM KCl, 1 mM MgCl2 buffer at pH 7.0. Direct transient kinetic measurements of rhodamine phalloidin binding to actin filaments indicate an association rate constant of 2.8 x 10(4) M-1 s-1 and a dissociation rate constant of 4.8 x 10(-4) s-1. The ratio of the rate constants yields a dissociation equilibrium constant of 17 nM. From equilibrium measurements, the apparent affinity of rhodamine phalloidin for actin filaments is 116 nM. The difference between the affinities determined by equilibrium and kinetic experiments is attributed to the depolymerization of filaments at low actin concentrations in the equilibrium samples. The binding stoichiometry is one rhodamine phalloidin molecule per actin subunit. When myosin subfragment-1 and tropomyosin are bound to actin filaments, the rate constants for rhodamine phalloidin binding are the same as for actin alone and in agreement with the binding affinities measured in equilibrium experiments. Presumably these proteins stabilize the filaments. Neither substitution of CaCl2 for MgCl2 nor the inclusion of 20 mM phosphate altered the rate or equilibrium constants. PMID- 7981199 TI - Mutational analysis of the substrate binding site of human complement factor D. AB - Complement factor D is a serine protease with a single natural substrate, C3b complexed factor B, and very low catalytic activity against synthetic esters. The recently solved X-ray crystal structure of factor D has demonstrated certain key differences from other serine protease in the conformation of residues of the catalytic triad and the substrate-binding regions. To investigate possible contributions of unique amino acid substitutions to these distinct structural and functional features of factor D, we constructed a series of mutants by substituting trypsin substrate-binding residues for the corresponding factor D residues. Wild-type and seven mutant factor D cDNAs were expressed stably in Chinese hamster ovary cells, and the recombinant proteins were purified from culture supernatants and assayed by hemolytic, proteolytic, and esterolytic assays. The combined results indicate that residues Thr-198, Ser-199, Arg-202, and perhaps also Val-203 provide determinants for substrate binding and catalysis. The data also provide additional support for the hypothesis that the proteolytically active conformation of the active center of factor D is induced by its substrate, C3bB. PMID- 7981200 TI - A metastable state of Torpedo californica acetylcholinesterase generated by modification with organomercurials. AB - Chemical modification of Torpedo californica acetylcholinesterase by various sulfhydryl reagents results in its conversion to one of two principal states. One of these states, viz., that produced by disulfides and alkylating agents, is stable. The second state, produced by mercury derivatives, is metastable. At room temperature, it converts spontaneously, with a half-life of ca. 1 h, to a stable state similar to that produced by the disulfides and alkylating agents. Demodification of acetylcholinesterase freshly modified by mercurials, by its exposure to reduced glutathione, causes rapid release of the bound mercurial, with concomitant recovery of most of the enzymic activity of the native enzyme. In contrast, similar demodification of acetylcholinesterase modified by disulfides yields no detectable recovery of enzymic activity. Spectroscopic measurements, employing CD, intrinsic fluorescence, and binding of 1-anilino-8 naphthalenesulfonate, show that the state produced initially by mercurials is "native-like", whereas that produced by disulfides and alkylating agents, and after prolonged incubation of the mercurial-modified enzyme, is partially unfolded and displays many of the features of the "molten globule" state. Arrhenius plots show that the quasi-native state produced by organomercurials is separated by a low (5 kcal/mol) energy barrier from the native state, whereas the partially unfolded state is separated from the quasi-native state by a high energy barrier (ca. 50 kcal/mol). Comparison of the 3D structures of native acetylcholinesterase and of a heavy-atom derivative obtained with HgAc2 suggests that the mercurial-modified enzyme may be stabilized by additional interactions of the mercury atom attached to the free thiol group of Cys231, specifically with Ser228O gamma with the main-chain nitrogen and carbonyl oxygen of the same serine residue. PMID- 7981201 TI - Reciprocated matrix metalloproteinase activation: a process performed by interstitial collagenase and progelatinase A. AB - Gelatinase A, a member of the matrix metalloproteinase (MMP) family, is secreted possessing an 80 amino acid N-terminal propeptide that must be removed in order to generate the active enzyme. Purified progelatinase A was activated to 38% of maximum by a 6 h incubation at 37 degrees C with equimolar concentrations of trypsin-activated interstitial collagenase (another MMP). The increase in activity was accompanied by cleavage of the M(r) 72,000 progelatinase A to the M(r) 66,000 active enzyme that has Y81 as its N-terminus. At low concentrations, progelatinase A was processed via an inactive intermediate, suggesting that its activation is a biphasic process. This was confirmed by the action of collagenase on proE375-->A (a mutant of progelatinase A that cannot become active) because, in this instance, only an M(r) 68,000 species with L38 as the N-terminus was produced. The remaining propeptide amino acids to Y81 could be readily removed by added active gelatinase A, indicating that collagenase works by generating an intermediate that is susceptible to autolytic activation. Although relatively slow, the rate of activation could be increased approximately 10-fold by the addition of 100 micrograms/mL heparin. This binds to the C-terminal domain of collagenase and progelatinase A and presumably acts as a template that positions the reactants close to one another. Collagenase activated by trypsin retains 8 or 14 amino acids of its propeptide.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7981202 TI - Sequence 18-29 on actin: antibody and spectroscopic probing of conformational changes. AB - Experimental evidence for the involvement of the 18-29 site within actin subdomain-1 in the actomyosin weak binding interface includes the inhibition of actomyosin ATPase activity by specific peptide antibodies [Adams, S., & Reisler, E. (1993) Biochemistry 32, 5051-5056] and by the Dictyostelium actin mutant D24H/D25H [Johara, M., et al. (1993) Proc. Natl. Acad. Sci. U.S.A. 90, 2127 2131]. In this work, the effect of the 18-29 peptide antibodies on the polymerization and conformation of actin has been characterized. Binding of antibody to the 18-29 site strongly inhibited the MgCl2-induced polymerization of G-actin, had a much weaker impact on the CaCl2 polymerization of actin, and showed very little effect on the NaCl polymerization of G-actin. These observations were linked to the binding of the 18-29 antibody to the different forms of actin. In sedimentation assays, the (18-29) IgG bound more strongly to Mg-F- and Mg-G-actins than to Ca-F- and Ca-G-actins, respectively. The binding of IgG to F-actin decreased sharply with an increase in ionic strength. Antibody binding to the 18-29 site induced conformational changes within the nucleotide cleft, both slowing the rate of nucleotide exchange and increasing the fluorescence intensity of actin-bound epsilon ATP. The increased fluorescence of a dansyl probe attached to Gln-41 and a pyrene probe attached to Cys-374 demonstrated that antibody binding also caused local perturbations in the DNase I loop of subdomain-2 and at the C-terminus of actin. These results are discussed in terms of actin plasticity and its implications for actomyosin interactions. PMID- 7981204 TI - Design of potent bivalent thrombin inhibitors based on hirudin sequence: incorporation of nonsubstrate-type active site inhibitors. AB - Hirudin from medicinal leech is the most potent and specific thrombin inhibitor from medicinal leech with a K(i) value of 2.2 x 10(-14) M. It consists of an active site blocking moiety, hirudin1-48, a fibrinogen-recognition exo-site binding moiety, hirudin55-65, and a linker, hirudin49-54, connecting these inhibitor moieties. Synthetic inhibitors were designed based on the C-terminal portion of hirudin. The bulky active site blocking moiety, hirudin1-48, was replaced by small nonsubstrate-type active site inhibitors of thrombin, e.g., dansyl-Arg-(D-pipecolic acid). The linker moiety was replaced by omega-amino acids of (12-aminododecanoic acid)-(4-aminobutyric acid), and hirudin55-65 was used as a fibrinogen-recognition exo-site binding moiety in most of the inhibitors. The crystal structure of the inhibitor in complex with human alpha thrombin showed that dansyl, Arg, and D-pipecolic acid of the active site blocking moiety occupy S3, S1, and S2 subsites of thrombin, respectively, and were therefore designated as P3, P1, and P2 residues. The use of dansyl-Arg-(D pipecolic acid) improved the affinity (K(i)) of the inhibitor 10-100-fold (down to 1.70 x 10(-11) M) compared to that of the similar compounds having D-Phe-Pro Arg as their substrate-type inhibitor moiety (K(i) = 10(-9)-10(-10) M). The linker connected to P2 residue eliminated the scissile peptide bond. The inhibitor was also stable against human plasma proteases. Further inhibitor design revealed that the toxic dansyl group could be replaced by 4-tert butylbenzenesulfonyl group and 1- or 2-naphthalenesulfonyl group for in vivo studies.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7981203 TI - Assignment and calcium dependence of methionyl epsilon C and epsilon H resonances in cardiac troponin C. AB - The 10 Met methyl groups in recombinant cardiac troponin (cTnC) were metabolically labeled with [13C-methyl]Met and detected as 10 individual cross peaks using two-dimensional heteronuclear single- and multiple-quantum coherence (HSMQC) spectroscopy. The epsilon C and epsilon H chemical shifts for all 10 Met residues were sequence-specifically assigned using a combination of HSMQC and systematic conversion of the Met residues to Leu. The only negative functional consequence of these changes was seen when both Met 45 and 81 were mutated. Binding of Ca2+ to the high affinity C-terminal sites III and IV induced relatively large changes in the epsilon H and epsilon C chemical shifts of all Met residues in the C-terminal domain as well as small but significant changes in the chemical shifts of epsilon H Met 47 and Met 81 in the N-terminal half of cTnC. Binding of Ca2+ to the low affinity N-terminal site II induced large changes in the epsilon H and epsilon C chemical shifts of Met 45, Met 80, and Met 81. Binding of Ca2+ to site II had no effect on the chemical shifts of Met residues located in the C-terminal domain. The nature of the chemical shift changes of Met residues in the N- versus the C-terminal halves of cTnC were consistent with different Ca(2+)-induced conformational changes in these domains. Thus, the assigned methyl Met chemical shifts can serve as useful structural markers to study conformational transitional in free cTnC and potentially after association with small ligands, peptides, and other troponin subunits. PMID- 7981205 TI - Interaction of the Shiga-like toxin type 1 B-subunit with its carbohydrate receptor. AB - A study of the binding of the Shiga-like toxin 1 (SLT-1) to the P(k) trisaccharide [methyl 4-O-(4-O-alpha-D-galactopyranosyl)-4-O-beta-D- glucopyranoside] and its constituent dissacharides was carried out. The trisaccharide represents the carbohydrate recognition domain of the neutral glycolipid receptor of the SLT-1, globotriosylceramide (GbOse3). The binding constant for soluble trisaccharide to the soluble pentameric B-subunit is weak, with a K(a) of (0.5-1) x 10(3) M-1 for B-subunit monomer. Scatchard analysis of the binding data indicates five identical non-interacting carbohydrate binding sites per B-subunit pentamer and no cooperativity in binding. Despite weak binding (delta G = -3.6 kcal mol-1), the enthalpy of binding (delta H = -12 kcal mol-1) and the change in molar heat capacity accompanying binding (delta C(p) = 40 eu) are comparable to other protein-carbohydrate interactions. Dynamic light scattering studies indicate that carbohydrate binding induces protein aggregation. At carbohydrate concentrations where > 90% of B-subunit monomers are bound, the far-UV CD spectra were unchanged, whereas a change in the near-UV CD, maximal near 270 nm, titrated to give an apparent binding constant in good agreement with that obtained by isothermal microcalorimetry. Steady-state fluorescence and fluorescence lifetime measurements indicated that the environments of the central tryptophans are perturbed during saccharide binding, and the changes correlate with the extent of protein aggregation. On the basis of the thermodynamics of binding, optical spectroscopy, and binding-induced aggregation, we propose a model of SLT-1-membrane interaction that relies on protein-carbohydrate interaction for specificity and protein-lipid interaction for tight binding. PMID- 7981206 TI - Electrostatic control of the substrate access channel in cytochrome P-450cam. AB - Camphor binding to ferric cytochrome P-450cam is a two-step process. The first step corresponds to the diffusion of camphor into the heme pocket, and the second one corresponds to an observable spin transition of the heme iron. In this paper, electrostatic interactions that may control the opening of the structure to allow substrate access to the buried and not solvent-exposed active site were examined. The electrostatic interactions occurring at the protein surface were weakened by increasing the ionic strength of the medium with sodium salts and strengthened by decreasing the dielectric constant of the medium with ethylene glycol as a cosolvent. The results obtained with the wild-type protein were compared to those obtained with the site-directed mutant of cytochrome P-450cam in which the Arg 186-Asp 251 and Lys 178-Asp 251 salt bridges, located at the entrance of the proposed access channel, were suppressed by replacing Asp 251 with an asparagine residue. Over a range of sodium chloride concentrations from 0 to 400 mM, camphor binding is favored, as seen in the variation in the first step dissociation equilibrium constant, K1d, which decreases from 49.5 to 24 microM, respectively. Addition of ethylene glycol favors the dissociation of the substrate-bound complex. The addition of sodium to the ethylene glycol-containing samples reverses the effect of the cosolvent. Removal of the Arg 186-Asp 251 and Lys 178 Asp 251 salt bridges results in an alteration in camphor binding in which K1d is equal to 34 microM without sodium.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7981207 TI - beta-Carotene quenches singlet oxygen formed by isolated photosystem II reaction centers. AB - By measuring time-resolved luminescence emission at 1270 nm, we have detected singlet oxygen formation by illuminated, reaction centers of photosystem II isolated from Pisum sativum, which is in agreement with earlier work (Macpherson, A. N., Telfer, A., Barber, J., & Truscott, T. G. (1993) Biochim. Biophys. Acta 1143, 301-309). In this paper we show that the yield of singlet oxygen is significantly increased if the number of beta-carotene molecules bound per isolated complex is reduced from two to one. We conclude, therefore, that beta carotene can act as an effective quencher of singlet oxygen in the photosystem II reaction center. This conclusion is supported by the finding that the rate of light-induced irreversible bleaching of chlorins in the reaction center is increased with decreasing beta-carotene levels. The results demonstrate the direct intermediacy of singlet oxygen in causing photooxidative damage within a biological environment and are discussed, specifically, in terms of the role of beta-carotene in protecting photosystem II against photoinhibition. PMID- 7981208 TI - Mossbauer and EPR studies of Azotobacter vinelandii ferredoxin I. AB - Azotobacter vinelandii ferredoxin I (FdI) is a small protein that contains one Fe4S4 cluster and one Fe3S4 cluster. Previous studies of FdI have shown that the redox potential of the Fe3S4 cluster and the MCD and CD spectra of the reduced Fe3S4 cluster are pH-dependent. Using Mossbauer and EPR spectroscopy, we have studied FdI in different oxidation states and at different pH values. Here, we report the spin Hamiltonian parameters of the oxidized (S = 1/2) Fe3S4 cluster at pH 7.4 and the reduced (S = 2) Fe3S4 cluster at pH 6.0 and 8.5. The pH dependence observed by MCD is also evident in the Mossbauer spectra which show a change of the magnetic hyperfine tensor for one Fe site of the valence-delocalized pair. The Fe4S4 cluster is ligated by cysteines 20, 39, 42, and 45, but not by the adjacent cysteine 24. Treatment of FdI with 3 equiv of ferricyanide alters the Fe4S4 cluster, yielding a new species, [Fe4S4]'. The S = 1/2 EPR signal of [Fe4S4]' has previously been attributed to the formation of a cysteine disulfide radical from Cys24 and cluster sulfide. Here we show that the EPR signal is broadened by 57Fe, indicating that the electronic spin is significantly coupled to the cluster iron. Consistent with this, substantial magnetic hyperfine interactions are observed by Mossbauer spectroscopy. In addition, the average isomer shift of the four Fe sites is smaller for [Fe4S4]' than for [Fe4S4]2+, indicating that the oxidation is iron-based to at least some extent. Incubation of FdI with excess ferricyanide destroys the Fe4S4 cluster but leaves the Fe3S4 cluster intact. Our studies of (3Fe)FdI show that the S = 1/2 spin of the Fe3S4 cluster interacts with another paramagnet, presumably a radical generated at the site left vacant by the removal of the Fe4S4 cluster. PMID- 7981209 TI - Comparison of native and mutant proteins provides a sequence-specific assignment of the cysteinyl ligand proton NMR resonances in the 2[Fe4S4] ferredoxin from Clostridium pasteurianum. AB - A sequence-specific assignment is presented for the eight low-field paramagnetically shifted cysteinyl ligand proton NMR resonances in the 2[Fe4S4] ferredoxin from Clostridium pasteurianum. The assignment is based upon comparison of chemical shifts in 1D and 2D NMR spectra of native oxidized protein and those of three mutants. The mutant proteins G12A and G41A were designed to produce minor local structural changes (hence small chemical shift perturbations) in either cluster I (glycine 12 to alanine) or in cluster II (glycine 41 to alanine). Observed chemical shift changes in spectra of the double mutant G12,41A support the interpretation. The comparison is aided by structural models derived from the crystal structure of the related ferredoxin from Peptococcus aerogenes. Each of the eight low-field resonances is assigned to a beta-proton from a different cysteinyl ligand, and so connectivities established from previous TOCSY and HMQC data allow assignment of all 24 cysteinyl ligand protons. PMID- 7981211 TI - A reassessment of the structure of chymotrypsin inhibitor 2 (CI-2) using time averaged NMR restraints. AB - Chymotrypsin inhibitor 2 (CI-2) is one of the growing family of proteins for which well-defined solution and crystal structures have been published and for which small, but distinct differences between these were found. It presents an ideal case to address the question of whether a structural difference is physically real or due to the simplifying approximations with respect to averaging that are used in the conventional methods for structure refinement. NOE distance and 3J coupling constant restrained molecular dynamics simulations were performed using conventional and time-averaged restraints, both in vacuo and in aqueous solution, and the trajectories were compared with structural properties of published structures. The time-averaged restrained molecular dynamics simulations sampled more conformations at various times and visited states consistent with both previously published solution and crystal structures. It was found that the difference between these structures is due to the refinement methodology used. Application of time-averaged restraints in structure refinement yields a physically different picture of the molecular mobility. PMID- 7981210 TI - Isoforms of the EP3 subtype of human prostaglandin E2 receptor transduce both intracellular calcium and cAMP signals. AB - The EP3 subtype of prostaglandin E2 receptor transduces diverse physiological responses in mammalian tissues through signaling pathways coupled to heterotrimeric G proteins. Distinct cDNA clones encoding five isoforms of the EP3 receptor were isolated from a human uterus cDNA library. The human EP3 receptor isoforms designated hEP3-I, I', II, III, and IV are derived from alternative RNA splicing and differ only in the distal sequences of their carboxyl-terminal cytoplasmic tails. The unique cytoplasmic tails consist of 31 amino acids for isoforms I and I', 29 for II, 6 for III, and 15 for IV. When stably expressed in CHO cell transfectants, all isoforms exhibited similar EP3-specific binding of [3H]-PGE2 and PGE2 analogs. The EP3-selective agonist M&B 28767 both decreased the intracellular cAMP concentration ([cAMP]i) and increased the intracellular concentration of calcium ([Ca2+]i) with quantitative differences among different isoforms, but none mediated an increase in [cAMP]i. Pertussis toxin treatment completely blocked the decrease in [cAMP]i, but not the increase in [Ca2+]i evoked by M&B 28767. PGE2-induced desensitization of [3H]PGE2 binding by isoforms III and IV was rapid and transient, whereas that by isoform II was slow and persistent. Reverse transcription-PCR amplification of EP3 receptor messages in human kidney and uterine tissue RNA detected expression of all isoforms with different abundancies. The dual signal transduction pathways and distinctive tissue distribution of isoforms of the EP3 receptor are consistent with its mediation of diverse functions of PGE2. PMID- 7981212 TI - Effect of an intersubunit disulfide bond on the stability of Streptomyces subtilisin inhibitor. AB - The effect of an engineered disulfide bond between two identical subunits of a dimeric protein, Streptomyces subtilisin inhibitor, on the stability of the protein was studied by differential scanning calorimetry. The introduction of the linkage caused a large stabilization without changing the cooperativity of unfolding, with the denaturation temperature of a 2 mg/mL solution being increased by 14.3 degrees C to 95.0 degrees C at pH 9.5 and by 16.4 degrees C to 63.0 degrees C at pH 3.0. The stabilization was caused by a loss of denaturational entropy, i.e., -40 and -98 cal K-1 mol-1 at pH 3.0 and 9.5, respectively, which more than compensated for the loss in the denaturational enthalpy. PMID- 7981213 TI - Analysis of circular dichroism spectra of oriented protein-lipid complexes: toward a general application. AB - A new application of circular dichroism on oriented films of protein-lipid complexes is presented in this work, which provides quantitative information on the orientation of alpha-helices with respect to the incident light beam. We used literature reference circular dichroism spectra for the various secondary structures to develop a new set of spectra, where the different directions of absorption within the molecular axis frame for each secondary structure type are taken into account. Using this new set of spectra, we could determine the orientation of the helical part of melittin in oriented films composed of various phospholipids. The orientation of the helix axis is found to be perpendicular to the membrane normal of films of dioleoylphosphatidylcholine, dioleoylphosphatidylglycerol, and dioleoylphosphatidylserine, whereas the helix was aligned preferentially parallel to the membrane normal for membranes composed of dimyristoylphosphatidylcholine and dimyristoylphosphatidylglycerol at a hydration of approximately 2-4 water molecules per lipid. The orientations found by circular dichroism at this low hydration for the various systems agreed very well with those obtained by Fourier transform infrared measurements on these samples. Upon increasing the hydration of the film (to approximately 20 water molecules per lipid), it is shown by circular dichroism that the orientation of the helix of melittin changes most in films of dioleoylphosphatidylserine, where it adopted, under these conditions, a preferred parallel orientation with respect to the membrane normal. Complications in the analysis of circular dichroism spectra of oriented samples are discussed and illustrated using patches of native purple membrane containing bacteriorhodopsin and films of alamethicin in dioleoylphosphatidylserine membranes. PMID- 7981214 TI - Orientation of the alpha-helices of apocytochrome c and derived fragments at membrane interfaces, as studied by circular dichroism. AB - The orientation of the different helical regions of the mitochondrial precursor protein apocytochrome c has been studied using circular dichroism on isolated fragments of this protein associated with oriented films composed of various phospholipids [de Jongh, H. H. J., Goormaghtigh, E., & Killian, J. A. (1994) Biochemistry (preceding article in this issue)]. Both the N and C terminus adopt helical structures in a membrane environment. The middle region can also be helical, but only in the presence of the N-terminal domain of the protein. In the presence of the unsaturated lipids dioleoylphosphatidylcholine and dioleoylphosphatidylglycerol, all three helices are found to have a preferred orientation perpendicular to the membrane normal, whereas in the presence of the saturated lipids dimyristoylphosphatidylcholine and dimyristoylphosphatidylglycerol, the terminal helices are preferentially oriented parallel to the membrane normal. In films composed of dioleoylphosphatidylserine, it is found that the N-terminal helix is oriented preferentially perpendicular, whereas the C-terminal helix is aligned more parallel to the membrane normal. The differences in preferred orientation between the terminal helices are demonstrated by molecular modeling of the helices at a water-lipid interface. The results are discussed in light of the translocation of apocytochrome c over the outer mitochondrial membrane, an important step in the import process of this protein in mitochondria. PMID- 7981215 TI - Rhodopsin kinase: studies on the sequence of and the recognition motif for multiphosphorylations. AB - Peptides of 10-12 amino acids in length, which overlapped with the sequence of the last 20 amino acids in the C-terminal tail of rhodopsin, were synthesized and used as substrates for rhodopsin kinase. In all cases the phosphorylation of the peptides was found to be greatly stimulated (> 20-fold) by the presence of light activated rhodopsin (Rho*). The incorporation of 32P at seven Ser/Thr residues that are the potential sites of phosphorylation was quantified, and the results were analyzed in terms of two parameters. First, a global comparison of phosphorylation at each site was made when the propensity for the modification was found to be in the order: Ser 343 > Ser 338 > Thr 336 > Ser 334, Thr 342 > Thr 335, Thr 340. Second, the peptides were aligned on a hypothetical template with the residue to be phosphorylated occupying the P-position, and the manner in which the nature of the surrounding residues effected the phosphorylation was assessed. It was found that the optimal phosphorylation of the P-site Ser/Thr occurs if it has at least one residue on the amino side and five on the acyl side and also contains a neutral residue, preferably small (A, P, S, T) at the P+4 position.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7981216 TI - Lysine 182 of endothelin B receptor modulates agonist selectivity and antagonist affinity: evidence for the overlap of peptide and non-peptide ligand binding sites. AB - The potent vasoactive peptide hormone endothelin (ET) binds to receptors which belong to the G-protein coupled receptor family. The availability of non-peptide antagonists for ET receptors allows investigation of the relationship among the binding sites for peptide and non-peptide ligands. In this study, a lysine residue, conserved within transmembrane domain 3 (TM3) of the ETA and ETB receptor subtypes, is implicated in agonist and antagonist binding by its analogous position within TM3 to a binding site aspartate residue conserved within bioactive amine receptors. Replacement of this lysine within hETB by arginine, alanine, methionine, aspartate, or glutamate results in hETB variants with unaltered affinities for agonist peptide ET-1 but which have affinities for peptide agonists ET-2, ET-3, sarafotoxin 6C, and TRL 1736 which are between 1-3 orders of magnitude lower than their corresponding wild-type hETB values. Significantly, the affinities of non-peptide antagonists, (+/-)-SB 209670 and its analogs as well as Ro 46-2005, are abrogated. The results suggest that an interaction of K182 of hETB with the indan 2-carboxyl of (+/-)-SB 209670 may contribute to the high-affinity binding of the diarylindan antagonists. The results indicate that TM3 of hETB is a region of overlap among the binding sites of non-peptide antagonists and the affected peptide agonists. PMID- 7981217 TI - Kinetic mechanism of adenine nucleotide binding to and hydrolysis by the Escherichia coli Rep monomer. 1. Use of fluorescent nucleotide analogues. AB - The Escherichia coli Rep helicase catalyzes the unwinding of duplex DNA in a reaction that is coupled to ATP binding and hydrolysis. The Rep protein is a stable monomer in the absence of DNA but dimerizes upon binding either single stranded or duplex DNA, and the dimer appears to be the functionally active form of the Rep helicase. As a first step toward understanding how ATP binding and hydrolysis are coupled energetically to DNA unwinding, we have investigated the kinetic mechanism of nucleotide binding to the Rep monomer (P) using stopped-flow techniques and the fluorescent ATP analogue, 2'(3')-O-(N-methylanthraniloyl-ATP (mantATP). The fluorescence of mantATP is enhanced upon Rep binding due to energy transfer from tryptophan. The results are consistent with the following two-step mechanism, in which the bimolecular association step is followed by a conformational change in the P-mantATP complex: P + mantATP [formula: see text] P mantATP [formula: see text] (P-mantATP). The following rate and equilibrium constants were determined at 4 degrees C in 20 mM Tris.HCl (pH 7.5), 6 mM NaCl, 5 mM MgCl2, and 10% (v/v) glycerol: k+1 = (1.1 +/- 0.2) x 10(7) M-1 s-1; k-1 = 3.2 (+/- 0.5) s-1; k+2 = 2.9 (+/- 0.5) s-1; k-2 = 0.04 (+/- 0.005) s-1; K1 = k+1/k-1 = (3.4 +/- 0.8) x 10(6) M-1; K2 = k+2/k-2 = 73 (+/- 10); Koverall = K1K2 = (2.30 +/- 0.6) x 10(8) M-1. Similar rate and equilibrium constants are obtained with mantATP gamma S, whereas the apparent rate constant for mantAMPPNP binding is 15 fold lower than for mantATP and equilibrium binding is weaker (Koverall approximately 10(6) M-1). Rep monomer does bind mantATP in the absence of Mg2+ (Koverall approximately 5 x 10(5) M-1), although the four rate constants in the above reaction increase by at least 8-fold (k-1 and k-2 increase by approximately 100- and approximately 1000-fold, respectively). The affinities of Mg2+ for P mantATP and (P-mantATP)* are 10- and 1000-fold higher than those for nucleotide free Rep monomer, indicating that the second step in the reaction is associated with a marked increase in Mg2+ affinity. The bound Mg2+ in a (P-mantATP)*-Mg2+ complex dissociates at a rate that is comparable to the rate of mantATP release.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 7981218 TI - Kinetic mechanism of adenine nucleotide binding to and hydrolysis by the Escherichia coli Rep monomer. 2. Application of a kinetic competition approach. AB - The Escherichia coli Rep protein is a DNA helicase that functions as a homodimer to catalyze the unwinding of duplex DNA during DNA replication in a reaction that is coupled to the binding and hydrolysis of ATP. As a first step toward a molecular understanding of the interactions of Rep with adenine nucleotides, we have investigated the kinetic mechanism of adenine nucleotide binding to the Rep monomer, which is the state of the protein in the absence of DNA. Although ATP binding to Rep does not significantly change the intrinsic tryptophan fluorescence, the binding of the fluorescent nucleotide analogue, 2'(3')-O-(N methylanthraniloyl)-ATP (mantATP) is associated with a large increase in mant nucleotide fluorescence intensity [lambda ex = 290 nm, lambda em > 420 nm; Moore, K. J. M., & Lohman, T. M. (1994) Biochemistry (preceding article in this issue)]. We have used the fluorescence signal from mantATP binding to monitor the kinetics of nonfluorescent nucleotide binding to Rep by a kinetic competition approach. The simultaneous and parallel binding of a mixture of mantATP and ATP to the Rep monomer is associated with a complex triphasic fluorescence transient during the approach to equilibrium. Global analysis of the fluorescence transients over a range of [ATP] by numerical integration techniques was used to define the kinetic mechanism of ATP binding and to determine the elementary rate constants. Using this approach, the kinetic rate constants for ADP, ATP gamma S, AMPPNP, AMP, adenosine, and inorganic phosphate were also determined at 4 degrees C in 20 mM Tris.HCl (pH 7.5), 6 mM NaCl, 10% (v/v) glycerol, and 5 mM MgCl2. The kinetics of adenine nucleotide binding to the Rep monomer are similar to those observed with the mant nucleotides under identical experimental conditions (Moore & Lohman, 1994). The kinetic competition data are consistent with the following two-step mechanism for the binding of ATP, ADP, and ATP gamma S, where P is the Rep monomer and A is the adenine nucleotide: P+A [formula: see text] P-A [formula: see text] (P-A). In the presence of 5 mM MgCl2, the values of K+1 (approximately 10(7) M-1 s-1) and k+2 (approximately 10 s-1) are comparable for each nucleotide, whereas k+2 > k-1 for ATP and ATP gamma S while for ADP k+2 << k-1; hence, differences in the overall equilibrium binding affinities of these nucleotides are primarily due to changes in k-1.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 7981219 TI - Costabilization of peptide and RNA structure in an HIV Rev peptide-RRE complex. AB - An arginine-rich peptide corresponding to amino acids 34-50 of the human immunodeficiency virus Rev protein has been shown to bind specifically to its RNA binding site (RRE) when the peptide is in an alpha-helical conformation. Mutation of any one of six amino acids (Thr34, Arg35, Arg38, Arg39, Asn40, or Arg44) was shown to strongly decrease specific RNA-binding affinity in vitro, suggesting that these residues may contact specific bases or distinct structural features of the RNA. We now show that the four arginine side chains, and not just their charge, are important for specific binding in vivo, and present evidence that three additional arginines (Arg46, Arg48, and Arg50) may make electrostatic contacts to the RRE. RNA-binding specificity of the Rev peptide is temperature dependent in vitro, correlating with alpha-helix unfolding. Circular dichroism experiments indicate that the peptide helical structure is stabilized when bound specifically to the RRE and that the RNA undergoes a conformational change upon binding. Because the structures of the peptide and RNA in this model system appear to be mutually stabilized upon binding, it is suggested that the entire complex may be viewed as a single folding unit. PMID- 7981220 TI - Biophysical characterization of the c-Myb DNA-binding domain. AB - We have examined proteins containing the DNA-binding domain of c-Myb with biophysical methods. This DNA-binding domain consists of three imperfect repeats (R1, R2, and R3) conserved among many species. Our results indicate that the DNA binding domain forms unspecific and specific complexes with oligodeoxynucleotides. In the presence of R1, DNA sequences related to a canonical c-Myb-binding site are better discriminated. Furthermore, although R2 and R3 are sufficient for sequence-specific DNA binding, a structural change of the DNA-binding domain upon specific complex formation is induced only when R1 is present. Therefore, R1 might serve as an important element required for secondary structure alteration upon binding and its stabilization as well as for better discrimination between specific and related DNA sequences. PMID- 7981221 TI - The mouse androgen receptor gene contains a second functional promoter which is regulated by dihydrotestosterone. AB - The androgen receptor (AR) is a developmental and tissue-specific transcription factor which is activated by binding testosterone or dihydrotestosterone. Several different methods of transcriptional regulation of the AR have been shown, including regulation by androgens, follicle-stimulating hormone, epidermal growth factor, and the cAMP pathway. In order to further characterize the transcriptional regulation of the AR, portions of the mouse androgen receptor (mAR) promoter were cloned into the promoterless pBLCAT3 vector and assayed for chloramphenicol acetyltransferase activity. The results indicate that in addition to the previously characterized promoter (+1) there is a second distinct promoter located 3' to the first promoter. Amplification of the 5'-end of the AR gene indicates that RNA originating from the second promoter is initiated from 162 and 170 bases downstream from the 5'-most previously characterized site. Northern blot analysis indicated that RNA initiated from the two promoters is differentially expressed in several cell lines and multiple tissues. Androgen ablation by castration showed that both promoters are controlled by androgens in the kidney. Sequence analysis revealed that the second promoter does not contain a TATA or CAAT box. Further characterization of this promoter may provide important insights into the transcriptional regulation of the androgen receptor since previous studies have often included only the first promoter. PMID- 7981222 TI - Characterization of the HeLa cell DNA polymerase alpha-associated Ap4A binding protein by photoaffinity labeling. AB - The ubiquitous dinucleotide diadenosine tetraphosphate (Ap4A) has been proposed to be involved in DNA replication and cell proliferation, DNA repair, platelet aggregation, and vascular tonus. A protein binding to Ap4A is associated with a multiprotein form of DNA polymerase alpha (pol alpha 2) in HeLa cells. We have purified the pol alpha-associated Ap4A binding protein to homogeneity. The Ap4A binding protein is resolved into two polypeptides of 45 and 22 kDa, designated as A1 and A2, respectively. We have utilized [alpha-32P]8-N3-Ap4A to label the purified binding protein, and by cross-linking the photoaffinity label we have determined that Ap4A binds to the A1 subunit. No binding to the ligand is observed with the A2 subunit. Photoaffinity labeling is saturated with approximately 0.4 microM photolabel, with a half-maximal binding at 0.15 microM. The labeling is UV-dependent and is competed by both 8-N3-Ap4A and Ap4A. Photoaffinity labeling is not affected in the presence of dATP and dGTP and is reduced only in the presence of excess of ATP indicating the specificity of the protein for Ap4A. Of the diadenosine polyphosphates, Ap4A and Ap5A competed for binding, while Ap2A and Ap3A did not compete for binding. Further, the presence of at least one adenosine may be necessary since Ap4G competes but Gp4G does not compete for binding to the protein. Various methylene bisphosphonate and thiophosphate analogs of Ap4A were tested to see their effect on photoaffinity labeling with 8-N3-Ap4A. Significant differences were observed among the various analogs in their ability to prevent the photoaffinity labeling of the ligand to the binding protein. PMID- 7981223 TI - Folding mechanism of ribonuclease T1 in the absence of the disulfide bonds. AB - In the absence of its two disulfide bonds, ribonuclease T1 can exist in a native like folded conformation when > or = 2 M NaCl is present. We measured the kinetics of unfolding and refolding of two reduced and carboxymethylated variants of ribonuclease T1 with one cis proline (the Ser54Gly/Pro55Asn variant) and with two cis prolines (the wild-type protein) as a function of the NaCl concentration. Single and double mixing techniques were used. Analysis of the kinetic results demonstrates that the two cis prolyl bonds at Pro39 and Pro55 remain cis in the folded state after the reduction and carboxymethylation of the disulfide bonds. Folded molecules with trans isomers could not be found. The substitution of cis Pro55 influences the proline-limited folding reaction, and the analysis of the changes in the folding kinetics shows that the trans-->cis isomerizations of both prolines are slow and are rate-determining steps for the refolding of ribonuclease T1 in the presence as well as in the absence of the disulfide bonds. The direct folding reaction of protein chains with correct prolyl isomers is also affected by the Ser54Gly/Pro55Asn mutation. The rate of refolding is decreased, whereas the rate of unfolding is almost unaffected. The kinetic analysis points to two main consequences of the Ser54Gly/Pro55Asn mutation for the stability and the folding mechanism of RNase T1. It is moderately destabilizing, because the deletion of a conformationally restricted residue (Pro55-->Asn) and the insertion of a flexible residue (Ser54-->Gly) both tend to increase the entropy of the unfolded state. The cis<-->trans isomerization of Pro55 is abolished, however, leading to a decrease in the entropy of the unfolded protein. These two entropic contributions seem to partially compensate each other, and the net change in free energy as a consequence of the Ser54Gly/Pro55Asn double mutation is very small. PMID- 7981224 TI - Mammalian DNA polymerases alpha, beta, gamma, delta, and epsilon incorporate fialuridine (FIAU) monophosphate into DNA and are inhibited competitively by FIAU Triphosphate. AB - Fialuridine [FIAU, 1-(2'-deoxy-2'-fluoro-beta-D-arabinofuranosyl)-5- iodouridine] was used in clinical trials for chronic hepatitis B virus infection and was extremely toxic. Evidence suggested targets of FIAU toxicity included mitochondria, but toxic mechanisms were unclear. Since FIAU is a thymidine analog, we reasoned that triphosphorylated FIAU (FIAUTP) could be incorporated into mitochondrial DNA by DNA pol-gamma and into genomic DNA by DNA polymerases alpha, beta, delta, and epsilon. All five purified mammalian DNA polymerases incorporated FIAUMP into the nascent DNA chain during in vitro DNA synthesis. When FIAUTP was substituted for dTTP, oligonucleotide products were generated efficiently by DNA pol-gamma and were similar to those generated in the presence of the four normal dNTPs. In contrast, oligonucleotide products generated by the four nuclear DNA polymerases in the presence of FIAUTP were significantly reduced in length relative to those generated in the presence of dTTP. In parallel kinetic assays, FIAUTP competitively inhibited the accumulation of radiolabeled dTTP into DNA by DNA pol-gamma. The Ki with DNA pol-gamma was 0.04 microM, the lowest Ki among the mammalian DNA polymerases. Competition between FIAUTP and dTTP and the relative ease of accumulation of FIAUMP in mitochondrial DNA by DNA pol-gamma in vitro together may relate to clinical FIAU toxicity. PMID- 7981225 TI - ATPase kinetics of recombinant bovine 70 kDa heat shock cognate protein and its amino-terminal ATPase domain. AB - Steady-state kinetic, pre-steady-state kinetic, and equilibrium binding measurements have been applied to determine the rate constants of individual steps of the ATPase cycle for the recombinant bovine 70 kDa heat shock cognate protein and its amino-terminal 44 kDa ATPase fragment. At 25 degrees C, pH 7.0, in the presence of 75 mM KCl and 4.5 mM Mg2+, the measured association rate constants for MgATP approximately hsc70 and MgADP approximately hsc70 are (2.7 +/ 0.5) x 10(5) and (4.1 +/- 0.5) x 10(5) M-1 s-1, respectively, while the dissociation rate constants are 0.0114 (+/- 0.0002) and 0.0288 (+/- 0.0018) s-1, respectively. MgATP (Kd = 0.042 microM) therefore binds to hsc70 more tightly than MgADP (Kd = 0.11 microM). ADP release is inhibited by inorganic phosphate (Pi), suggesting that product dissociation is ordered with Pi released first and ADP second. The rate of chemical hydrolysis of ATP is 0.0030 (+/- 0.0003) s-1 for hsc70 and 0.0135 (+/- 0.0033) s-1 for the 44 kDa fragment. The rate of Pi release is 0.0038 (+/- 0.0010) s-1 for hsc70 and 0.0051 (+/- 0.0006) s-1 for the 44 kDa fragment. For the 44 kDa fragment, Pi release is the slowest step in the ATPase cycle, while for hsc70, Pi release and chemical hydrolysis of MgATP have similar rates; in both cases, ADP release is a relatively rapid step in the ATPase cycle. PMID- 7981226 TI - Substrate specificity of porcine renin: P1', P1, and P3 residues of renin substrates are crucial for activity. AB - Renin, the rate-limiting enzyme in the formation of angiotensin II, is well-known for its stringent substrate specificity. In this study, the biochemical basis for the unusual specificity of renin was investigated by replacing individual amino acids in the octapeptide substrate of renin with Ala. Kinetic analyses of Ala substituted substrates revealed that the substitutions did not cause significant changes in the Km values, but did cause variable changes in the kcat and kcat/Km values. Ala substitutions at the P1', P1, and P3 sites decreased the kcat/Km values by 400-700-fold. Similar substitutions at the P3', P2, P4, and P5 sites only reduced the kcat/Km values by 2-7-fold. Interestingly, Ala substitution for the P2' Val produced a substrate with an approximately 3-fold increase in activity. These results indicate that the P1', P1, and P3 residues are crucial in determining the substrate specificity of renin. The findings also suggest that the specificity of renin is achieved mainly through substrate discrimination in the transition state, rather than in the ground state. Further studies on the effects of amino acid substitutions at the P2' site revealed that non-branched chain amino acids (e.g., Ala and alpha-aminobutyric acid) are preferred at this site. Only P1' substitution demonstrated any significant change in Km, presumably due to the decreased hydrophobic interactions in the S1' site upon Ala substitution. The species specificity of renin presumably arises from differing P1'-P3' residues in angiotensinogens. For example, the P1'-P3' residues from human and porcine angiotensinogens are Ile-Val-His and Leu-Val-Tyr, respectively.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7981227 TI - Isotopic analysis of the reaction catalyzed by glycerol dehydrogenase. AB - Glycerol dehydrogenase catalyzes the reversible NAD(+)-dependent oxidation of glycerol to form dihydroxyacetone. Initial velocity, product, and dead-end inhibition studies performed for the forward and reverse reactions support an ordered kinetic mechanism with NAD+ binding first and NADH released last. A monovalent cation is required for enzymatic activity and glycerol binding, with K+ having the highest activity as measured by V. The pH dependence of the kinetic parameters V and V/Kglycerol, as well as the temperature dependence of the V pH profile, suggested that an enzymic carboxylate group functions as a base in catalysis. The pH dependence of the primary deuterium kinetic isotope effect shows that DV/Kglycerol increases from a pH-independent value of 1.15 at high pH values to a pH-independent value of 2.44 at low pH values. DV exhibits a similar pH dependence, increasing from a pH-independent value of 2.57 at high pH values to a pH independent value of 4.88 at low pH values. A chemical mechanism for enzymatic glycerol oxidation is proposed based on the data. PMID- 7981228 TI - Deoxycytidine kinase is phosphorylated in vitro by protein kinase C alpha. AB - Deoxycytidine (dCyd) kinase was effectively phosphorylated by protein kinase C. The reaction was rapid, occurring at 4 degrees C as well as at 37 degrees C and approximately 0.7 mol of phosphate could be incorporated per mol of deoxycytidine kinase. Phosphoserine was the primary amino acid to be phosphorylated. Phosphorylation of deoxycytidine kinase resulted in a 100% increase in the Vmax using dCyd as a substrate (52.16 +/- 1.3 versus 104.47 +/- 11.4 nmol/min/mg protein), and an increase in the apparent Km (2.0 +/- 0.2 microM versus 6.9 +/- 1.2 microM). The inactive antimetabolite, ara-C, is activated within a cell by deoxycytidine kinase phosphorylation of the prodrug. Recent studies have shown that ara-C activates protein kinase C in vivo [1]. Furthermore, ara-C has been shown to be metabolized to ara-CDP-choline via reversal of the cholinephosphotransferase [2] producing diglyceride, a cellular activator of protein kinase C. Thus, in situ, deoxycytidine kinase may be phosphorylated by protein kinase C with the result that self-potentiation of ara-C toxicity may occur via increased activity of deoxycytidine kinase. PMID- 7981229 TI - Leukotriene C4 upregulates collagenase expression and synthesis in human lung fibroblasts. AB - Leukotriene C4 (LTC4), a mediator generated by a variety of inflammatory cells, participates in several physiological and pathological processes. It has been shown that LTC4 stimulates collagen synthesis by fibroblasts, suggesting a role in collagen turnover. However, the possible effect of this mediator on collagen degradation has not been examined. In this study we explored the role of LTC4 in the modulation of fibroblast interstitial collagenase and TIMP-1. Confluent cultures of three human normal lung fibroblast cell lines, and one derived from idiopathic pulmonary fibrosis (IPF) were exposed to LTC4 0.1, 1 and 10 nM, and to IL-1 beta as positive control. Collagenase and TIMP mRNAs expression were analyzed by Northern blot followed by densitometric scanning. Immunoreactive procollagenase was detected by immunoblot, and collagenase activity was measured using [3H]collagen. Our results showed that LTC4 enhanced several-fold collagenase mRNA expression in collagenase-producing fibroblasts, and induced the expression of the enzyme mRNA in collagenase-nonproducing fibroblasts, both in normal and IPF derived cell lines. LTC4 1 nM induced the highest response. Collagenolytic activity and immunoreactive collagenase paralleled collagenase mRNA expression. Interestingly, simultaneous exposure of fibroblasts to LTC4 plus IL-1 failed to show additive effects. Moreover, in two cell lines the combination resulted in a decrease of collagenase mRNA expression compared with both mediators separately. TIMP mRNA levels were not significantly modified by LTC4, nor IL1 beta. Our findings suggest that LTC4 plays a role in the modulation of fibroblast collagenase, and it may participate in extracellular matrix remodeling during lung inflammation. PMID- 7981230 TI - Phencyclidine inhibits epinephrine-stimulated platelet aggregation independently of high affinity N-methyl-D-aspartate (NMDA)-type glutamatereceptors. AB - The psychotomimetic analgesic phencyclidine (PCP), which binds to a high affinity site on the neuronal N-methyl-D-aspartate (NMDA)-sensitive glutamate receptor, has previously been found to bind to platelets with high affinity and to specifically delay the onset of epinephrine-stimulated platelet aggregation (Jamieson et al. (1992) Biochem. J. 285, 35-39). We have now shown that the rank order of binding affinities of 14 synthetic PCP analogs at the high affinity binding site on platelets does not parallel the rank order of their affinities in binding to rat brain membranes, indicating that the high affinity PCP binding sites in platelets is distinct from the neuronal NMDA receptor. The order of potency of six of these analogs in delaying the onset of epinephrine-stimulated platelet aggregation also did not parallel the rank order of their binding affinities for platelet or brain binding sites. These data indicate that the ability of PCP analogs to inhibit epinephrine-stimulated aggregation is not related to their ability to bind to the high affinity platelet PCP binding site. Furthermore, (+)MK-801, which binds to the same high affinity binding site in neurons as does PCP, failed to inhibit epinephrine-stimulated platelet aggregation, further suggesting that the site at which PCP acts in platelets is not related to the NMDA-type glutamate receptor. Further studies showed that 5 HT2 receptors and effects on platelet secretion are not involved in PCP-mediated inhibition of epinephrine-induced platelet aggregation. PMID- 7981231 TI - Hematopoietic colony stimulatory factor formation by murine mesangial cells: gene expression and biological activity. AB - This study examined the ability of mesangial cells to synthesize colony stimulating factors (CSF), cytoregulatory peptides associated with the differentiation and proliferation of hematopoietic cells. Conditioned media obtained from SV-40 transformed murine mesangial cells stimulated the growth of murine bone marrow progenitor cells of the myeloid series. Differential analysis of these cells showed the presence of both macrophages and granulocytes. Cellular identification of bone marrow colonies stimulated in response to mesangial cell conditioned media was examined by flow cytometric analysis and revealed the presence of F4/80 antigen positive macrophages (67%) and Gran-1 antigen positive granulocytes (21%). Neutralizing antibodies to macrophage colony-stimulating factor (M-CSF) and granulocyte-macrophage colony-stimulating factor (GM-CSF) but not antibody to interleukin-3 (IL-3), or stem cell factor (SCF) significantly inhibited the growth of the progenitor cells induced by mesangial cell conditioned media. Utilizing Northern blot analysis, murine mesangial cells expressed mRNA transcripts for M-CSF, GM-CSF, and granulocyte colony-stimulating factor (G-CSF). Further studies were performed to determine optimal incubation conditions for mesangial cell CSF gene expression. These studies revealed that both GM-CSF and G-CSF mRNA were maximally expressed at early time points (4 and 8 h of incubation), while M-CSF mRNA expression remained unchanged during the incubation of mesangial cells from 4-48 h. Incubation of mesangial cells with various concentrations of fetal bovine serum (FBS, 0.5-15%) markedly increased the mRNA expression of M-CSF, GM-CSF and G-CSF in a dose-dependent manner. These studies indicated that transformed murine mesangial cells are able to synthesize and secrete biologically active CSF that are associated with the migration and proliferation of circulating mononuclear cells in the glomerulus. Furthermore, observations regarding the role of duration of incubation and the media concentration of FBS on mesangial cell CSF mRNA expression may provide useful data to understand the optimal conditions for studies that examine the gene expression of basal or inducible CSF in mesangial cells. PMID- 7981232 TI - Amino acid deprivation-induced stress response in the bovine renal epithelial cell line NBL-1: induction of HSP 70 by phenylalanine. AB - Amino acid deprivation of the bovine renal epithelial cell line NBL-1 led to a range of responses by the heat shock and glucose regulated stress proteins. The classic heat shock induction of HSP 72 was found to be mimicked, without prior heat stress, by phenylalanine addition to cells simultaneously deprived of all other amino acids. Co-inclusion of alanine prevented the HSP 72 induction by phenylalanine but not that caused by heat stress. Phenylalanine also increased expression of HSP 70 mRNA in cells simultaneously deprived of other amino acids. The glucose regulated protein GRP 75 was increased upon amino acid deprivation. GRP94 was detectable in a 50 kDa form in control cells but was detected as a 94 kDa form upon amino acid deprivation which was further enhanced upon inclusion of phenylalanine. Addition of alanine to the starvation medium led to detection of the 50 kDa form only. Amino acid deprivation appears to mimic the glucose deprivation stress response. Inclusion of phenylalanine during amino acid deprivation leads to a stress response similar to that of heat shock in terms of HSP 72 induction. However, the two inducers are sensitive to different repression signals since only the phenylalanine-signal was subject to nihilation by alanine co-inclusion. PMID- 7981233 TI - Stimulation of protein synthesis and phospholipase D activity by vasopressin and phorbol ester in L6 myoblasts. AB - The effects of 12-O-tetradecanoylphorbol-13-acetate (TPA) and vasopressin on protein synthesis and phospholipase D (PLD) activity were investigated in L6 myoblasts. TPA stimulated a concentration-dependent increase in protein synthesis (EC50 approx. 10 nM) during a 90 min incubation, but had no effect after 6 h. The maximum increase was about 15% and was mediated through changes in translation, as TPA had no effect on RNA accretion and the response was not prevented by actinomycin D. TPA also stimulated PLD activity as measured by an 8-fold increase in the formation of phosphatidylbutanol (PtdBuOH) and the release of choline (EC50 5-10 nM). In contrast to TPA, vasopressin stimulated protein synthesis (maximum increase 30%, EC50 approx. 10 nM) and RNA accretion after 6 h, but had no effect after 90 min. Vasopressin also increased PtdBuOH production 4-5-fold (EC50 approx. 0.5 nM) and choline release (EC50 approx. 1 nM). The addition of a highly purified preparation of PLD (2-10 units/ml) from Streptomyces sp. to L6 cells stimulated a concentration-dependent increase in choline release and protein synthesis after both 90 min (maximum stimulation 13%) and 6 h (maximum stimulation 12%). PLD also stimulated RNA accretion after 6 h but not 90 min. The data support a role for PLD in the regulation of protein synthesis in L6 cells. PMID- 7981234 TI - Glycogen synthesis from glucose by direct and indirect pathways in hepatocyte cultures from different nutritional states. AB - The conversion of glucose to glycogen by direct and indirect pathways was determined from the incorporation of [6-3H,U-14C]glucose into glycogen in hepatocyte cultures isolated from fed, fasted or fasted-refed rats. Mercaptopicolinate, an inhibitor of phosphoenolpyruvate carboxykinase (PEPCK) was used to determine the extent by which 6-tritium is lost by mechanisms not involving flux through PEPCK. Glucose conversion to glycogen was lower in hepatocytes from fasted and higher in hepatocytes from fasted-refed rats than in hepatocytes from rats fed ad libitum. Insulin increased glycogen synthesis in hepatocytes from all nutritional states, and it decreased the 3H/14C ratio incorporated into glycogen. This increased loss of 6-tritium was only in part mercaptopicolinate-sensitive. Lactate and pyruvate (2 mM + 0.2 mM) increased glycogen deposition, largely by stimulation of glucose conversion to glycogen by the direct pathway. Insulin-induced glucokinase mRNA expression was higher in hepatocytes from fed than from fasted or refed rats whereas PEPCK mRNA expression was lowest in hepatocytes from fasted-refed rats. Hepatocyte cultures derived from different nutritional states express differences in glycogen synthesis from glucose by direct and indirect pathways as well as differences in the extent by which pyruvate cycling accounts for loss of 6-tritium. PMID- 7981235 TI - Control of glucose metabolism in newborn pig enterocytes: evidence for the role of hexokinase. AB - The objective of the present work was to identify the regulatory step(s) in the post-natal development of a high glycolytic capacity previously evidenced in newborn pig enterocytes (Darcy-Vrillon et al. (1994) Pediat. Res., 36, 175-181. Glucose entry via the Na+/glucose cotransporter, estimated by the uptake of the non-metabolizable analogue methyl alpha-D-[U-14C]glucopyranoside, slightly decreased between birth and 2 days of sucking. The flux of glucose metabolized into the pentose cycle pathway slightly increased but could not account for the 3 fold increase observed in the glycolytic capacity. Whereas the maximal activity of 6-phosphofructo-1-kinase did not change between stages, there was a significant increase in hexokinase activity as well as in the flux of glucose phosphorylated. These findings suggest that the stimulation of glucose phosphorylation through hexokinase is the key event leading to an increased glycolytic capacity of small intestinal cells at the onset of sucking. PMID- 7981236 TI - The role of protein kinase C in arachidonic acid release and prostaglandin E production from CHO cells transfected with EGF receptors. AB - Arachidonic acid release and prostaglandin production are stimulated by both phorbol esters and growth factors in various cell types. Whereas phorbol esters activate and transmit a signal via protein kinase C, this pathway is not necessarily involved in growth factor signal transduction. We investigated the involvement of protein kinase C in the pathway of arachidonic acid metabolism by CHO cells transfected with full-length EGF receptor (CHOwt). Two isoforms of protein kinase C were identified in CHOwt cells, alpha and zeta. On downregulation, the parallel loss of phorbol ester-stimulated arachidonic acid release and the alpha-isoform suggests a possible involvement of this isoform in phospholipase A2 activation in these cells. In addition, we propose that the zeta isoform may be separately involved in prostaglandin production as residual phorbol ester-stimulation of PGE production occurs in downregulated cells where PKC zeta is the sole remaining isoform. EGF stimulation of arachidonic acid release, as a measure of phospholipase A2 activation, and subsequent prostaglandin production are unaffected by inhibition of protein kinase C in CHOwt cells. Indeed one such inhibitor, staurosporine, augmented the EGF effect. These results suggest that PKC is not required for EGF activation of phospholipase A2 in these cells. PMID- 7981237 TI - 23Na nuclear magnetic resonance study of intracellular sodium in vascular endothelial cells. AB - 23Na(+)-NMR was used to determine the intracellular mobility and cell membrane permeability of Na+ in porcine vascular endothelial cells. The cells were grown as monolayers onto microcarrier beads and perfused with a medium containing Dy(P3O10)2(7-) to shift the extracellular from the intracellular Na+ resonance. Using triple quantum coherence filtered NMR experiments and spin echoes, it was shown that not all intracellular Na+ ions are in the extreme narrowing limit. The triple quantum coherence filtered experiments resulted in an observed R2f = 2022 +/- 302 s-1 and R2s = 200 +/- 28 s-1. From spin-echo experiments we obtained R2f = 2200 +/- 355 s-1 and a R2s = 145 +/- 15 s-1. These values are similar to those found in other cell systems and indicate water-Na(+)-protein interactions. Using single quantum NMR, the Na+ permeability of the endothelial membrane was determined. To obtain the Na+ transcellular permeability coefficient the cells were treated with 50 microM ouabain in the perfusion medium. Ouabain inhibits the Na-K pump and caused the intracellular Na+ concentration to increase in time. The permeability coefficient was obtained from the time dependence of the intracellular Na+ concentration. Assuming a monolayer of rectangularly shaped cells, we obtained a value of P = 0.02.10-5 cm s-1. PMID- 7981238 TI - Analysis of successive endocytic compartments isolated from Dictyostelium discoideum by magnetic fractionation. AB - A colloidal iron probe was fed to the amoeba Dictyostelium discoideum and chased for different intervals. Successive segments of the endocytic pathway were then isolated magnetically at high yield and purity. There were approx. 500 endocytic vacuoles per cell; their diameters increased from approx. 0.1-0.2 microns after 3 min of feeding to approx. 2 microns after 15 min of feeding and 60 min of chase. The wave-like progression of ingested probes along the endocytic pathway suggested that the transfer of cargo involved a maturation mechanism rather than the shuttling of cargo between stable compartments. The lifetime of primary pinosomes was calculated to be approx. 1 s. Multivesicular bodies were common in the 3 min fraction and abundant in 15 min lysosomes. alpha- and beta-adaptins of molecular masses of approx. 89 and 83 kDa were richer in the 3 min vesicles than in plasma membranes and later endocytic vacuoles. Acid phosphatase, intrinsic vacuole acidity, the vacuolar proton pump protein and pump activity were present at all endocytic stages but rose between the 3 min and 15 min vacuoles and declined thereafter. Bis(monoacyglycero)phosphate or BMP, a lipid characteristic of lysosomes, followed a similar time course; it contributed up to half of the total lipid in lysosomal vacuoles. We conclude that there is both continuity and differentiation along this endocytic pathway. PMID- 7981240 TI - Role of capsaicin, curcumin and dietary n-3 fatty acids in lowering the generation of reactive oxygen species in rat peritoneal macrophages. AB - Reactive oxygen species (ROS) generated by activated macrophages play an important role in the initiation of inflammation. Ten different spice principles, some of which with known anti-inflammatory properties, were tested for their effect on generation of superoxide anions, hydrogen peroxide and nitrite radical generation by activated rat peritoneal macrophages. Preincubation of macrophages with 10 microM capsaicin (from red pepper) or 10 microM curcumin (from turmeric) completely inhibited the superoxide anions, hydrogen peroxide and nitrite radical production in vitro by macrophages. Higher concentrations (500 microM) of eugenol (from clove) and piperine (from pepper) were required to completely inhibit superoxide anion and hydrogen peroxide release by macrophages. Capsaicin and curcumin were then fed to rats which were on a diet containing 8 wt% of coconut oil or olive oil or peanut oil or cod liver oil for 8 weeks, by gavage for 2 weeks. The peritoneal macrophages isolated from these animals produced lower levels of ROS compared to the macrophages from the control groups fed with the oil alone. Macrophages from cod liver oil fed animals generated lower levels of superoxide anions (76%), hydrogen peroxide (70%) and nitrite radicals (88%) compared to those isolated from coconut oil fed animals. Peanut oil and olive oil feeding also lowered the extent of ROS generation in macrophages compared to those from coconut oil fed animals. Capsaicin and curcumin feeding further lowered the generation and release of ROS. It is concluded that capsaicin or curcumin in combination with dietary fatty acids differentially lowers the production of ROS in macrophages. PMID- 7981239 TI - Hydrolysis of cell surface inositol phospholipid leads to the delayed stimulation of phosphatidylinositol synthesis in bovine aortic endothelial cells. AB - In order to address the issue of how inositol phospholipid synthesis is controlled in a resting cell we looked for enhanced [3H]phosphatidylinositol (PtdIns) labelling in response to the hydrolysis of cell surface PtdIns. Bacillus thuringiensis PtdIns-PLC when added to intact bovine aortic endothelial (BAE) cells rapidly hydrolysed 9.1 +/- 1% of the total cellular PtdIns. This result suggests that BAE cells have a cell surface pool of PTdIns. Hydrolysis of cell surface PtdIns, in contrast to the agonist-stimulated hydrolysis of inner leaflet PtdIns, did not lead to a rapid (minutes) stimulation of PtdIns resynthesis. Prolonged incubation of BAE cells with PtdIns-PLC led to further hydrolysis of PtdIns (up to 20% of total cellular PtdIns). This second phase of PtdIns-PLC induced hydrolysis was inhibited by the addition of brefeldin A suggesting that it was dependent on vesicular traffic to the plasma membrane from the endoplasmic reticulum. Furthermore, the above result suggests that prolonged incubation of intact cells with PtdIns-PLC leads to the slow depeletion of intracellular PtdIns stores. This second phase of PtdIns-PLC induced hydrolysis was associated with PtdIns resynthesis since prolonged incubation with PtdIns-PLC, but not B. cereus PtdCho-PLC (which does not hydrolyse PtdIns), led to enhanced PtdIns labelling. The results indicate that extracellular PtdIns-PLC induced PtdIns resynthesis may occur due to PtdIns-PLC induced intracellular PtdIns depletion. PMID- 7981241 TI - Glutathione S-conjugate transport by cultured human cells. AB - Elimination of the products of xenobiotic metabolism is an important step in cellular detoxification and involves a specific transport system or "export pump". ATP-dependent transport of glutathione S-conjugates has previously been demonstrated in a variety of tissues, mainly from rat. However, the characteristics of this pump have not been fully explored in human cells. This study investigated transport of a glutathione S-conjugate, 2,4-dinitrophenyl glutathione (GS-DNP), by a variety of cultured human cell lines. GS-DNP was generated intracellularly after treatment of cells with 1-chloro-2,4 dinitrobenzene and subsequent transport of the conjugate into the extracellular medium was measured spectrophotometrically at 340 nm. Calculation of the initial transport rates at 37 degrees C revealed considerable variation in GS-DNP secretion between cell lines which was statistically significant in some cases. A 2-fold increase in GS-DNP efflux was observed between Jurkat and HL-60 cells (11.360 +/- 3.893 vs. 5.662 +/- 2.263 nmol/10(6) cells/h, P < 0.007). The highest rate of transport was found in HepG2 cells (14.171 +/- 4.790 nmol/10(6) cells/h) whereas the 5637 cell line had the lowest level with a transport rate of 1.475 +/ 0.631 nmol/10(6) cells/h. For each cell line, transport of GS-DNP was almost totally inhibited or markedly reduced on ice. Pre-incubation of cells at 42 degrees C also lowered the initial transport rates compared with cells maintained at 37 degrees C but these were not significantly different except in the case of HeLa cells. ATP levels ranged from 30.5 to 89.3 nmol/mg protein and there was variation in the glutathione content and glutathione S-transferase activities of the cells. This report demonstrates firstly that transport of glutathione conjugates is a feature of many cell types in vitro and secondly that the basal levels of GS-DNP secretion vary significantly between human cells. PMID- 7981243 TI - Signal recognition and transduction in olfactory neurons. PMID- 7981242 TI - Macrophages loaded with doxorubicin by ATP-mediated permeabilization: potential carriers for antitumor therapy. AB - In many cell types extracellular ATP (ATPe) has been shown to cause reversible plasma membrane permeabilization to low molecular weight (< 900 Da) water-soluble compounds. In the present report we have exploited this technique to incorporate the anticancer drug doxorubicin (DXR), molecular mass 543 Da, into the cytoplasm of two mouse cell lines that had previously been shown to express the ATPe-gated pore, J774 macrophages and tumor necrosis factor (TNF)-resistant L929 fibroblasts. Compared to passively loaded cells, ATPe-mediated reversible permeabilization allowed an at least 4-fold increase in DXR intracellular trapping (0.5 pg/cell versus 2 pg/cell). Analysis of the release kinetics at 37 degrees C showed that about 40% of total intracellular DXR was discharged during the first hour from both ATPe-permeabilized and passively loaded cells; about 15% further release was observed upon incubation up to 4 h. DXR release profiles were similar in ATPe-permeabilized and passively loaded cells. ATPe-permeabilized, DXR loaded (ATPe-DXR) cells strongly inhibited the proliferation of K562 tumor cells. Taken together these results indicate that ATPe-mediated reversible plasma membrane permeabilization can be effectively used to load cells of different histotypes with high concentrations of DXR. This approach could permit to vehicle high doses of anticancer agents by using living cells while reducing systemic toxic effects. PMID- 7981244 TI - Endothelin receptor agonists and antagonists exhibit different dissociation characteristics. AB - Endothelins (ETs) are vasoconstricting peptides that bind to membrane receptors to initiate their physiological effects. This report compares the dissociation characteristics of selected ET agonists and antagonists, and studies the effects of any difference in dissociation characteristics on the potency of antagonists. Competition studies using various ET receptor ligands against [125I]ET-1 or [125I]ET-3 binding demonstrated that porcine cerebellum membranes contain predominantly ETB receptor. [125I]IRL1620 associated with the receptors in a time dependent manner. Although bound [125I]IRL1620 was easier to dissociate than bound [125I]ET-3, both agonists exhibited a dissociation half life > 20 h. For non-radiolabeled ligands, bind-and-wash studies were employed in which membranes were pre-incubated with unlabeled ligand followed by extensive washing before assaying for [125I]ET-1 binding. Results from bind-and-wash studies confirmed that bound non-radiolabeled IRL1620 and ET were as difficult to dissociate as [125I]ligands. In contrast, bound PD142893 and Ro46-2005 were easily dissociated from ETB receptors. Consequently, the inhibitory effects of PD142893 and Ro46 2005 on [125I]agonist binding diminished following incubation time. In cloned human ETA and ETB receptors, bound ET-1 was also more difficult to dissociate than bound antagonists. These results suggest that the differences in the dissociation characteristics of ET receptor agonists vs. antagonists may account for the diminished potency of Ro46-2005 and PD142893 as a function of incubation time. PMID- 7981245 TI - PAF stimulates cAMP formation in P388D1 macrophage-like cells via the formation and secretion of prostaglandin E2 in an autocrine fashion. AB - The role of cAMP in the formation of prostaglandin E2 (PGE2) was investigated in bacterial lipopolysaccharide (LPS)-primed P388D1 macrophage-like cells stimulated with platelet activating factor (PAF). cAMP levels and PGE2 secretion were correlated with stimulation by PAF or ionomycin. Indomethacin inhibited cAMP formation induced by PAF, but not PGE2-stimulated cAMP production. Inositol (1,4,5)-trisphosphate levels were strongly reduced by exogenous PGE2 and increased by H-89, an inhibitor of PKA. However, exogenous PGE2 did not affect PAF-stimulated PGE2 formation. These results suggest that cAMP levels in P388D1 cells are regulated by PGE2 in an autocrine fashion. Evidence is presented that this feedback mechanism regulates inositol (1,4,5)-triphosphate levels in these cells, while PGE2 formation is not affected. PMID- 7981246 TI - Possible involvement of phosphatidylinositol-specific phospholipase C related to pertussis toxin-sensitive GTP-binding proteins during adipocyte differentiation of 3T3-L1 fibroblasts: negative regulation of protein kinase C. AB - Insulin/dexamethasone/methylisobutylxanthine (hormones/IBMX) induce 3T3-L1 fibroblasts to differentiate into adipocytes. Our previous study suggested that pertussis toxin (IAP)-sensitive GTP-binding protein(s) (G-protein) is involved in the process of differentiation by hormones/IBMX, accompanied by c-fos induction. Northern blotting indicated that among the IAP-sensitive G-proteins, the levels of Gi2 alpha, Go alpha, and Gi3 alpha mRNA were decreased, increased and unchanged, respectively. Gi1 alpha was undetectable and IAP attenuated the decrease in Gi2 alpha mRNA level but did not affect the change in Go alpha mRNA level during the adipocyte differentiation. These results indicate that IAP sensitive Gi2 alpha mRNA level is decreased during adipocyte differentiation. A combination of phosphatidylinositol-specific phospholipase C (PI-PLC) and IBMX induced c-fos expression in 3T3-L1 fibroblasts similar to that induced with hormones/IBMX. c-fos induced by both stimulators was also diminished by anti inositolglycan antibody or anti-PI-PLC antiserum. Insulin stimulated the release of inositolproteoglycan and diacylglycerol from 3T3-L1 fibroblasts, which was suppressed by IAP treatment. These findings suggested that one of the pathways of adipocyte differentiation induced by hormones/IBMX occurs via the inositolglycan specific PI-PLC cascade coupled to IAP-sensitive G-protein(s). Both activation of glycerophosphate dehydrogenase and stimulation of insulin-dependent 2 deoxyglucose uptake induced by hormones/IBMX were enhanced in protein kinase C depleted cells exposed to phorbol 12-myristate 13-acetate (PMA), and attenuated in IAP-treated cells. The level of a 32P-labeled 52 kDa protein in plasma membrane fractions immunoprecipitated by anti-PI-PLC antiserum was increased by PMA stimulation, abolished in PMA-treated cells, and increased in IAP-treated cells. These findings suggest that protein kinase C phosphorylates PI-PLC, resulting in a decrease in PI-PLC activity related to the signal transduction pathway of adipocyte differentiation of 3T3-L1 fibroblasts. PMID- 7981247 TI - Recovery from acute glucagon challenge in isolated rat hepatocytes: is protein dephosphorylation synchronous or asynchronous? AB - One-dimensional SDS-PAGE of cytosolic phosphopeptides confirms that glucagon promotes the phosphorylation of 11 phosphopeptides in isolated rat hepatocytes pre-equilibrated with 32PO4(3-). Nine of these phosphopeptides are tentatively identified, whereas two phosphopeptides (48 kDa and 46 kDa) remain unidentified. Transfer of the glucagon-challenged hepatocytes to medium free of 32PO4(3-) and glucagon led to the rapid net dephosphorylation of the phosphopeptides and to a rapid decline in the specific radioactivity of the [32P]ATP pool. There were profound differences between the post-glucagon rates of net dephosphorylation of the different hepatic phosphopeptides, consistent with net dephosphorylation being asynchronous during the recovery phase from acute glucagon challenge. On the basis of descending rates of dephosphorylation, four major groups of phosphopeptides were delineated. Okadaic acid, a potent inhibitor of protein phosphatase 2A and to a lesser extent protein phosphatase 1, inhibited the dephosphorylation of all of the phosphopeptides. A role for protein phosphatase 2A in protein dephosphorylation may be indicated by the observation that spermine, a specific activator of protein phosphatase 2A, stimulates the dephosphorylation of some, but not all, of the glucagon-stimulated phosphopeptides. Although phosphorylation during the recovery phase from glucagon challenge may be a complicating factor, the results suggest that post-glucagon dephosphorylation is a complex asynchronous process. The physiological consequences of this asynchrony may be that the suppression of glycogenolysis and gluconeogenesis and the activation of glycolysis are early events in the recovery process. PMID- 7981249 TI - An inflammatory bowel disease support group for teens and their parents. AB - In this article, the authors describe the steps in the development of a Crohn and colitis support group for teenagers age 11-18 years and their parents. The use of support groups has been described in the literature as a method of assisting families in dealing with the challenges of chronic illness. The Crohn's Disease and Colitis Foundation of America (CCFA) Self-Help Support Group design was modified to address the developmental needs of teens. Nine families agreed to attend six support group sessions (first hour: for education; second hour: for support). A survey at the end of the sessions indicated that the teens and their parents had more positive attitudes towards Inflammatory Bowel Disease as a result of their participation in the support group. The design for a support group for teens and families with Inflammatory Bowel Disease is a model applicable to other types of healthcare support groups. PMID- 7981248 TI - Platelet-activating factor induced calcium mobilization and phosphoinositide metabolism in cultured bovine cerebral microvascular endothelial cells. AB - Platelet-activating factor (PAF) is a powerful lipid autacoid with a variety of biological activities. More and more evidence suggests that PAF might play an important role in modulation of cerebrovascular system function, particularly during ischemia-induced cerebrovascular damage. However, the mechanisms involved in PAF actions on cerebrovascular or other brain cells are virtually unknown. Therefore, this study was designed to investigate PAF receptor-mediated cellular signal transduction in bovine cerebral microvascular endothelial (CME) cells with the aid of a potent PAF antagonist, WEB 2086. PAF induced an immediate and concentration-dependent increase in [Ca2+]i with an EC50 of 4.75 nM. PAF-induced [Ca2+]i mobilization was inhibited by PAF antagonist WEB 2086, in a dose dependent manner (IC50 = 15.53 nM). The calcium channel blockers diltiazem (10 microM) and verapamil (10 microM) had no effect on the PAF-induced increase in [Ca2+]i, but depletion of Ca2+ from the incubation buffer caused a 45.26% reduction of PAF-induced [Ca2+]i elevation. PAF stimulated phosphoinositide metabolism in a dose-dependent manner with an EC50 of 12.4 nM for IP3 formation, which was also inhibited by the PAF antagonist WEB 2086 in a dose-dependent manner with IC50 value of 16.97 nM for IP3 production. These data indicate that bovine CME cells respond to biologically relevant concentrations of PAF and this response involves activation of phospholipase C and increase in [Ca2+]i via specific PAF receptors. Our results may contribute to further understanding of the mechanism behind PAF actions on cerebrovascular cells. PMID- 7981250 TI - The impact of disposable equipment on room fee reimbursement for endoscopic retrograde cholangiopancreatography. AB - Disposable equipment is widely used in many gastroenterologic procedures. Such equipment decreases risks of cross contamination, is convenient, and decreases the processing, storage, and cost of reusable equipment. However, disposable equipment has a far-reaching environmental impact. Most disposable equipment must be handled as infectious waste. Moreover, cumulative costs associated with disposable equipment may be quite high. In this study, the authors attempted to delineate the percentage of room fee reimbursement spent on disposable equipment. The procedure selected for the study was Endoscopic Retrograde Cholangiopancreatography (ERCP). Two hundred forty-eight procedures were surveyed over a 6-month period between September 1992 and February 1993, and the total cost of each procedure was calculated. Reimbursement figures for diagnostic and therapeutic ERCPs were obtained for Medicare, contracted providers, and private payors. The percentage of room fee reimbursement monies used for disposable equipment for diagnostic ERCPs ranged from 5.8 to 12.8%. For disposable equipment in therapeutic ERCPs the percentage of room fee reimbursement monies ranged from 40.5 to 59.7%. Combining both diagnostic and therapeutic ERCPs, the percentage of room fee reimbursement to defray the cost of disposable equipment was 42.4%. Disposable equipment costs are a large portion of the room fee reimbursement. leaving potentially inadequate revenues for salaries, general upkeep of equipment, and capital to buy new or replace aging equipment. PMID- 7981251 TI - Liver biopsy and nursing intervention. AB - A liver biopsy is valuable in evaluating for liver disease. A biopsy is often the determining factor for final diagnosis. The Mengbini Klatskin and Tru-Cut needles are types of biopsy needles used in the GI department at the University of Rochester. The choice is based on the personal preference of the physician or on the type of biopsy. The RN's role in the GI department includes pre- and post procedure planning, assistance during the procedure, patient and family education, and emotional support. It is important to develop a trusting rapport with patients undergoing a liver biopsy. In addition, confident assistance with the procedure and correct positioning of the patient lead to a successful procedure as well as to an uneventful recovery. In searching the literature, the authors found little current information to assist nurses in the assessment of patients about to undergo a liver biopsy. In this article, the authors present some recommendations from experience to assist others in providing quality patient care for liver biopsy procedures. PMID- 7981252 TI - Healthcare reform: impact on gastrointestinal endoscopy units. AB - Healthcare costs, which now comprise 13.4% of the United States gross national product, continue to increase. President Clinton has placed healthcare reform on the national agenda, sparking nationwide debate. The President's plan will have an impact on all healthcare providers. As a result of this proposal, changes in the health care delivery system are occurring. The endoscopy setting will not be immune to these changes. In this article, the authors explore the possible impact of healthcare reform on nurses in general and, in particular, nurses in the endoscopy setting. PMID- 7981253 TI - Clinical applications of nuclear medicine in gastroenterology. AB - Nuclear medicine (NM) has traditionally been a non-nursing field. This specialty has grown rapidly and continues to expand. Most nurses have had very limited exposure to nuclear medicine, except in the area of patient preparation for the nuclear medicine department. Because this specialty has had significant advances that require patient monitoring in many diagnostic and therapeutic procedures, nurses will benefit by learning more about this field and by equipping themselves to care for pre- and postprocedural patients. This article is an overview of the nuclear medicine process and its most common clinical applications in the GI field as they relate to nursing practice. PMID- 7981254 TI - Yesterday is a dream--tomorrow is a vision--today is a beginning. PMID- 7981255 TI - Endoscopy down under. PMID- 7981256 TI - Levsin (hyoscyamine sulfate USP). AB - Levsin is an anticholinergic drug used in the treatment of irritable bowel syndromes, functional intestinal disorders, and as adjunct therapy in peptic ulcer disease. Levsin is also used parenterally to reduce duodenal motility to facilitate diagnostic studies. Levsin is readily absorbed through the gastrointestinal tract, reaches peak effects in 2-2.5 hr, and is excreted in the urine within 24 hr. PMID- 7981257 TI - Developing a paper for conference presentations. AB - Opportunities to expand the professional nursing role and present at conferences have increased. The purpose of this article is to share suggestions for developing and presenting papers. Essential ideas on who will present and how to write an abstract, deal with rejection or success, develop an outline, construct a lecture, select audiovisual materials, and use public speaking skills are described. The publishing and copyright processes are also discussed. Using these practical strategies will enable individuals to develop and/or enhance presentations. PMID- 7981258 TI - Writing a research proposal: the critical first step for successful clinical research. AB - The proposal is a key element in the thesis or clinical research project. It identifies what is to be studied, why the topic is relevant, and how the research will be conducted. The proposal is a detailed plan or "blueprint" for the intended study, and once it is completed, the research project should flow smoothly. Writing a proposal may seem like a daunting undertaking, but a little thought and preparation will make it easier. In this article, the author provides a sample research proposal and a set of instructions that the beginning researcher should find helpful. PMID- 7981259 TI - Outpatient quality assurance monitor: constipation/encopresis. AB - Quality Assurance (QA) programs assure that patients are getting the appropriate care, information, and support needed to produce better health outcomes. In this article, the authors describe monitoring nursing process by documentation of care in patients with constipation/encopresis. Longitudinal follow up to monitor patient outcomes completed the QA program. The process portion of the monitor was very successful, but the results of the outcome monitor were disappointing. PMID- 7981260 TI - Psychophysiological factors associated with irritable bowel syndrome. AB - Irritable bowel syndrome (IBS) is a functional gastrointestinal disorder with no known pathophysiological etiology. Many individuals with IBS, however, report higher than normal levels of stress and exhibit abnormal personality characteristics. In this article, the author reviews the psychophysiological factors associated with IBS and discusses gastrointestinal neuroendocrinology, the effects of stress on gastrointestinal motility, and the nursing implications related to this syndrome. PMID- 7981261 TI - Needle safety in an endoscopy unit. AB - Personnel in GI Endoscopy units are at higher risk than health care workers in general for exposure to Hepatitis B and Human Immunodeficiency Virus. Occupational Safety and Health Administration Standards require personal protective equipment including gloves, goggles, masks, water-impervious gowns, shoe covers, sharps containers, and biohazardous waste containers to be readily available. Special hazards in endoscopy make staff compliance both essential and challenging. Contaminated needle sticks are a common occupational injury in this setting, and one GI unit has developed several safeguards to increase staff's protection. These safeguards include inserting all intravenous lines in the safest, most accessible site: the right forearm; hanging IV fluids on all patients whose procedures are done in the radiology suite; and employing the needle recapping system that is cost-effective and easy to use in the endoscopy setting. PMID- 7981262 TI - Developing a staffing model. AB - Appropriate staff numbers are directly associated with the provision of safe patient care. Providing safe patient care is a concern shared not only by managers but by staff members as well. By using the information found in this article from relative value to daily diary time studies, the department manager will have the knowledge to ascertain the correct number of personnel needed to perform the work required. PMID- 7981263 TI - The Japanese gastroenterological endoscopy technician system. PMID- 7981265 TI - Versed administration for i.v. conscious sedation. PMID- 7981264 TI - Lessons in perseverance. PMID- 7981267 TI - [Thermally-induced changes in structure-kinetic properties of lactate dehydrogenase]. AB - Structural and functional properties of the lactate dehydrogenase modified by temperature at range 40-70 degrees C have been investigated. Kinetic principles of the thermoinactivation have been studied. The rate constants and the activation energy have been determined. Analysis of changes of the protein molecular mass leads to the conclusion that high-temperature denaturation of the lactate dehydrogenase (in investigated temperature interval) depends on oligomer molecule dissociation to monomers and subsequent aggregation of protein subunits. PMID- 7981266 TI - [Structure-activity changes in human hemoglobin induced by UV-light and serotonin]. AB - Basic indices of oxygen-binding properties of the human hemoglobin solutions modified by the UV-light (240-390 nm) in dose range 151-604 J/m2 together with serotonin (10(-5)-10(-3) mol/l) have been analysed by means of spectrophotometry registration of the oxyhemoglobin dissociation curves. In these conditions biogenic amine displays maximum photoprotective effect at the concentration 4 x 10(-4) mol/l. At the highest concentrations serotonin exert photosensibilitive that influences the course of the protein molecule disorganisation. It has been demonstrated that three-dimensional surfaces analysis can be used to forecast the influence of the serotonin photoprotection on the hemoglobin functional activity. PMID- 7981268 TI - [The effect of deformation on the catalytic activity of carboxypeptidase A in the crystalline state]. AB - A new approach to study of enzyme mechano-chemistry is proposed which is based on measuring of catalytic activity of crystalline cross-linked samples subject to uniaxial tension. Deformation of monoclinic P2(1) carboxypeptidase A crystals along [010] directions results in considerable increase of their esterase activity with no changes in the Michaelis constant. This can be explained as a consequence of considerable conformational changes accompanying the enzyme cycle. PMID- 7981269 TI - [Thermal restructuring and hydration of serum albumin]. AB - Calorimetry and dielectrometry in the millimeter wave range have been applied to demonstrate a possibility for determination of heat capacity of bound water in biopolymer matrices in solution is shown. Variation of the hydration level of human serum albumin caused by the variation of temperature and protein concentration is described. Application of two methods based on comparison of calorimetric and dielectric data on protein solutions at different temperatures and concentrations have produced similar values of the heat capacity of bound water in the protein hydration shell (approximately 3 J/g.K). PMID- 7981270 TI - [Acetylation of histones in vitro causes chromatin decompactization]. AB - It has been discovered that chemical acetylation of chromatin in vitro by acetyladenylate leads to decrease in the mobility of nucleosomal fiber fragments in agarose gel. Acetylation of HI-depleted chromatin does not produce this effect. Based on these results together with other available data, it is possible to conclude that acetylation causes decompactization of the chromatin fiber. A possible molecular mechanism of in vivo fiber decondensation and interaction of different chromatin compactization levels is discussed. PMID- 7981271 TI - [Dependence of the chromatin condensation process on the temperature and ionic strength of the media: investigation using gel electrophoresis in low density agarose]. AB - Conformational mobility of 30 nm nucleosomal fiber under temperature variations at different ionic strength of the medium has been analyzed. A new property of chromatin organization has been characterized, namely, nucleosomal solenoid condensation in response to increase of temperature. This property is analogous to salt-induced condensation and becomes particularly prominent at low ionic strength. In this context previously obtained data on changes in the DNA linking number of topological domains are discussed. It is concluded that these changes probably arise from modification of supernucleosomal level of chromatin organization. PMID- 7981272 TI - [Hydration and stability of the double helical complex poly(dA)-poly(dT)]. AB - IR-spectrometry and thermopiezogravimetry are used to study the structure formation and the water environment of the double-helix Na-poly(dA)-poly(dT) complex in films in the 0-100% interval of the relative humidity (RH). It has been found that three different structures of the complex are formed in the 0-32, 32-76 and 88-100% intervals of RH. The calculations of resonance frequencies of out-of-ring (C-0) and in-ring (C-N) vibrations in adenine and thymine using perturbation theory show that the second and the third forms are the X-ray beta B'- and alpha-B'-forms. Distribution of the binding energy of water molecules has been found from IRS data about water sorption and isotherms of hydration at different temperatures. The enthalpy of helix-coil transition has been found from microcalorimetry data. These results allow us to estimate the energy contribution of water molecules (about 75%) and other interactions (about 25%) in the total stabilization energy of the complex structure. PMID- 7981274 TI - [Analysis of geometric parameters and mechanical properties of erythrocytes by filtration through nuclear membrane filters. I. A mathematical model]. AB - A mathematical model is constructed, which quantitatively describes the rate of erythrocyte passage through pores of nuclear membrane filters during filtration of a diluted erythrocyte suspension upon action of a constant hydrostatic pressure. The following main factors have been taken into account: geometrical constraints linking the surface area of the erythrocyte membrane, the erythrocyte volume and the geometrical parameters of the filter pores; mechanical characteristics of the erythrocyte membrane; viscosity of the intracellular content. Analysis of the model allows us to conclude that it is possible to extract information about all above erythrocyte characteristics from the experimental curves describing, dependency of the filtration rate of the erythrocyte suspension from the osmoticity of the outer medium. PMID- 7981273 TI - [Structural and physicochemical characteristics of DNA from animal tissue subjected to chronic irradiation in the Chernobyl area]. AB - The properties of animal DNAs exposed to prolonged irradiation in the Chernobyl zone, have been studied by the methods of viscometry, thermal denaturation, IR spectroscopy, and electrophoresis. High content of low-molecular fractions have been observed in the preparations of DNA from liver and spleen, their quantities increasing with age and generation of animals. This effect is especially strong in DNA from liver. Low-molecular fraction of DNA is shown to be enriched with G-C pairs and to consist of the following four fractions: 1) approximately 500 base pairs (B.p.), 2) approximately 1.5 divided by 2 thousand B.p., 3) approximately 4 divided by 5 thousand B.p. and 4) a mixture of approximately 20 thousand B.p. fragments. Further, it has been observed that the DNA preparations from the tissues of experimental animals contain about ten times higher contents of Fe, Zn, Se and other elements as compared to the control preparations. PMID- 7981275 TI - [The effect of phenazine methosulfate on human erythrocytes]. AB - The experimental data about the phenazine methosulfate (PMS) effect on human erythrocytes are considered. It is demonstrated that PMS well penetrates the cells and causes changes dependent on incubation time. PMS may possess either oxidative or reducing properties according to experimental conditions. The PMS potency for oxidation is revealed in change of the haemoglobin redox state to more oxidative one (MetHb), in decrease of the reducing glutathione level and in increase of the reducing rate of potassium ferricyanide (RRPF). The use of erythrocytes oxidated by sodium oxide demonstrates the PMS reducing properties which cause reduction of methaemoglobin (MetHb) and decrease of the sodium oxide inhibitory effect on RRPF. Based on the obtained data a scheme is proposed for the PMS action on erythrocytes implying three interaction centres within the cells. PMID- 7981276 TI - [The effect of chlorine diffusion potential on electrophoretic mobility and erythrocyte sedimentation in diluted suspensions]. AB - Electrophoretic activity of human erythrocytes in isotonic medium with reduced NaCl content does not depend on the outer electric field strength when pH decreases from 7.3 to 5.5. At pH approximately equal to 5.3 the measured values of electrophoretic mobility drop with decrease of the outer electric field strength starting at 600-700 V/m. Simultaneously signs of the solitary settlement of erythrocytes diluted suspensions are disturbed. Estimated values of the chlorine diffusion potential in these conditions exceed the value 70-80 mV, at which the erythrocyte membrane permeability changes. It is suggested that the observed dependency of electrophoretic mobility on the field strength is caused by ion flows through the erythrocyte membrane leading to diffusion non equilibrium in the electrolyte layer close to the membrane. PMID- 7981277 TI - [Hemolysis of human erythrocytes by hemin. The role of hemin in erythrocyte autohemolysis]. AB - Hemin hemolysis of human erythrocytes at 37 degrees C has been investigated by the kinetic method. It has been observed that hemin affects erythrocytes by two mechanisms, inducing "quick" and "slow" hemolysis. The "quick" hemolysis is completed after the first few minutes. The final level of "quick" hemolysis is a function of relative hemin concentration. It is equal to zero when the latter is smaller than the minimum concentration Cmin = 10(8) molecules of added hemin per cell. The final level of "slow" hemolysis is always 100%. It is suggested that the limiting step of autohemolysis is the membrane proteins oxidation catalyzed by endogenous hemin originating from methaemoglobin during erythrocyte incubation at 37 degrees C. PMID- 7981278 TI - [Dependence of the rate of myofibril contraction on MgATP concentration. A theoretical examination]. AB - We propose simple model for the mechano-biochemical cycle of the myosin cross bridges, taking into account the contribution of "slow binding" bridges in the negative strength. Mathematical analysis of this model allows us to obtain an analytical expression for the dependence of the contraction velocity on the MgATP concentration. Parameters of this equation are rate constants of dissociation of "slow binding" bridges from thin filament, liberation of inorganic phosphate and binding of MgATP. The model leads to the bell-shaped dependence of myofibrillar contraction velocity on the substrate concentration similar to the experimental one. The values of above mentioned constants for the isolated myofibrils are estimated to be close to values obtained in unstructured contractile models. PMID- 7981279 TI - [Interaction of rat myocardial tissue with nitroxide radicals]. AB - Interaction of myocardium with nitroxide radicals (TEMPO, TEMPAMINE and TEMPOL) has been studied on the experimental model of Langendorf-perfused rat heart. Freezing of radical-containing hearts has been performed during their perfusion or after 40-min total ischemia. It has been shown that all the analyzed radicals are localized in lipid microenvironment in myocardium. Molecules of TEMPAMINE and TEMPOL are more immobilized, than TEMPO ones. It has been shown, that there are no changes in the microenvironment of the radicals and the character of their mobility in myocardium, caused by ischemia. PMID- 7981280 TI - [Threshold behavior of the blood coagulation system upon changes in calcium concentration]. AB - Dependence of the citrate human blood plasma clotting kinetics on free calcium concentration under its titration with calcium has been studied in vitro. Activation of factor XI is shown to be independent on calcium, while of thrombin concentration increases non-linearly at calcium concentrations in the range 0.2 0.3 mM. Kinetics of the thrombin generation fits well by the exponential function. Power indexes of the exponents rise steeply as calcium concentration increases from 0.2-0.5 mM and reach plateau at higher concentrations. At free calcium concentrations under 0.2 mM the thrombin level does not increase and remains lower than 10 pmol/ml as seen by our measuring system whose sensitivity threshold is surely less than 10 pmol/ml. Thus, the blood coagulation system behaves in a threshold manner under changes of calcium concentration. The threshold concentration of free calcium is equal to 0.2 mM. PMID- 7981281 TI - [Automatic regulation in the auditory analyzer and the phenomenon of accelerated growth of loudness]. AB - Physical analysis of the ear periphery structure and the data on loudness perception have been used to develop a model of loudness measurement and self control in the hearing analyzer. The experimental results obtained recently by different researchers are shown to confirm that the basic ideas of this model are reasonable, and the model is of considerable heuristic importance. The author provides treatment of the main hearing "paradox", that is the existence of a wide dynamic range of loudness perception for a narrow range of afferent pulsation in auricular nerve fibers. A simple explanation is found for the so-called adaptation phenomenon. The explanation of the phenomenon of loudness increase acceleration typical for many forms of neurosensory hypoacousis opens up new perspectives in the diagnostics and treatment of these diseases. PMID- 7981282 TI - [Biophysical mechanisms of toxicity of fluorocarbon emulsions]. AB - Intravenous administration of emulsions of some perfluorochemicals (PFCs) are followed by lung gas-exchange alterations, lung inflation and animal death. The emulsion toxicity can be caused by both low aggregation stability of the emulsion in the blood stream and appearance of the additional gas pressure in alveoli as a result of difference in the rates of alveolar gas and PFC vapor diffusion. Theoretical and experimental analysis shows that (1) absence of emulsion particle aggregation into blood stream, (2) low pressure of saturated vapors of PFC phase and (3) relatively low rate of PFC expiration from the organism are essential conditions for the creation of a safe fluorocarbon blood substitutes. PMID- 7981283 TI - [Dependence of the efficacy of slowing on the localization of inhibitory synapses on neuronal dendrites. Mathematical modeling]. AB - In the case of somatic inhibition the maximum efficiency of inhibition is observed when exciting inputs are situated distal of the long dendrite. For fibres of a medium length simultaneous inhibition in the soma and the distal end is more efficient. Excitant synapsis near the soma produce the best inhibition only at some fixed distance. This effect can explain the morphological fact of rarefaction of synaptic contacts near soma. PMID- 7981284 TI - [Animal behavior against a background of long period heliogeophysical fluctuations]. AB - Many Earth biological processes are immediately linked with the Cosmos, its matter and energy. Cosmic rays, which as noted by V.I. Vernadsky, come from all heavenly bodies, penetrate the whole Earth and everything on it. It is solar rays that dictate the main features of the planetary organisation of the biosphere, provide the free chemical energy, and determine the development of the organic world, cycles, rhythms and the great variety of this development. PMID- 7981285 TI - [Left-helical (PPII-PPII) type of globular protein structure: the level of the left helical type of poly-L-proline II in Kunitz trypsin inhibitor is no less than 43%. Experimental Reper spectrum of the extended left helix]. AB - There is established that the protein trypsin inhibitor Kunitz is a globular protein of (PPII-PPII)-type. The content of poly-L-proline helix is not smaller than 43%. It has been shown by CD method that the transition from an extended left-handed helical structure to alpha-helix arises on heating till the denaturation temperatures. On this assumption the CD spectrum of poly-L-proline II type has been calculated. PMID- 7981286 TI - [Value of molecular biology techniques in the study of nosocomial infections]. PMID- 7981288 TI - [Differential clinical characteristics among pediatric patients with gastroenteritis caused by rotavirus and adenovirus]. AB - BACKGROUND: The differential clinical and epidemiological characteristics of pediatric patients (< 14 years) with gastroenteritis caused by rotavirus or adenovirus were studied. MATERIAL AND PATIENTS: A retrospective study was performed in patients with viral gastroenteritis diagnosed from January 1990 to December 1992. The detection of viral particles was carried out by the agglutination system with latex particles sensitized with antibodies versus rotavirus and adenovirus. Clinical and epidemiological characteristics of the patients were collected reviewing the medical records and emergency charts. RESULTS: Two hundred eighty-nine patients corresponding to 240 cases of infection by rotavirus (83.1%) and 48 (16.9%) by adenovirus, were analyzed. Diarrhea by rotavirus predominated in the winter months (59.7% of the cases from December to March). Nonetheless, those caused by adenovirus were seen throughout the year with a stable incidence being observed. Statistically significant differences were seen in both groups (p < 0.001) with rotavirus infection having a greater tendency to admission and greater incidence of vomiting, fever (> 39 degrees C) and underlying disease. The presence of leukocytosis was different in the adenovirus group as were the greater length of duration of diarrhea prior to attending the Emergency Department (5.2 days) and the total length of stay (11.2 days). No other associated enteropathogenic organisms were detected in 86.3% of the infections by rotavirus and in the 89.8% of those caused by adenovirus. In regard to age group distribution prevalence of diarrhea by rotavirus was observed during the first 3 months of life (76.6%) while adenovirus group it went up to 24 months of age with similar percentages. CONCLUSIONS: Diarrhea by rotavirus is mainly presented in the winter, with vomiting and its shorter in length and the symptoms less prolonged than diarrhea caused by adenovirus. Rotavirus diarrhea generally affect patients admitted with some underlying disease. Nonetheless, microbiologic diagnosis is required to establish the definitive etiology of both clinical processes. PMID- 7981287 TI - [Microbiologic diagnosis of typhoid fever: report on an outbreak]. AB - BACKGROUND: The incidence of typhoid fever has greatly fallen in Spain although sporadic cases and limited outbreaks may be observed. The usefulness of the serum agglutinin studies for the diagnosis of this disease has been questioned by many authors. However, this diagnosis criteria continues to be used in Spain. The usefulness of blood cultures, stool cultures, urinecultures and serological test is herewith compared. METHODS: Three groups were prospectively studied: 18 patients with typhoid fever from one single outbreak, 50 blood donors, and 24 patients with other infections. Blood, stool culture, urinecultures and serology (agglutination) were carried out in the first group and in the other two groups serological test were used to determine the cut-off points and study cross reactions. RESULTS: Blood culture was found to be the most sensitive technique (94%) followed by stool culture (53%). No positive urineculture of seroconvesrion were observed. The cut off points accepted following the study of the donors were 1/160 or greater for the O antigen and 1/320 or greater for the H antigen. Two false positive for the O antigen and 3 for the H antigen were observed in the 24 patients with other infections. CONCLUSIONS: When suspecting typhoid fever, the combined use of blood culture and stool culture is recommended. The usefulness of serological test in our area lays in the observation of seroconversion associated to a compatible clinical picture. Its performance should not being considered as adequate in unspecific febrile syndromes. PMID- 7981289 TI - [Efficacy of gentamycin combined with beta-lactam antibiotics against penicillin resistant and non-resistant Streptococcus agalactiae]. AB - BACKGROUND: Evaluation of the incidence, tolerance and the bactericidal activity against penicillin, ampicillin, cefotaxime, gentamicin and the combination of penicillin plus gentamicin, ampicillin plus gentamicin, cefotaxime plus gentamicin and cefotaxime plus ampicillin in 22 clinical isolates of Streptococcus agalactiae. METHODS: Killing curves were performed. The concentrations of antibiotics was selected taking into account its level in cerebrospinal fluid. RESULTS: We detected 5 (22.7%) tolerant strains to penicillin and ampicillin and 2 of them (9.0%) were also tolerant to cefotaxime. Bactericidal activity was seen in a 100% of the strains against the association penicillin plus gentamicin, ampicillin plus gentamicin and cefotaxime plus gentamicin, being greater than the bactericidal activity against cefotaxime (77.3%), penicillin, ampicillin and cefotaxime plus ampicillin (54.5% respectively). CONCLUSIONS: Considering the high incidence of tolerance and the deficient bactericidal activity of the beta-lactam antibiotics against tolerant and no tolerant strains, it seems necessary to include gentamicin in the treatment of Streptococcus agalactiae severe infections. Several studies of experimental models must be performed to verify in vivo, the in vitro results. PMID- 7981290 TI - [Bacteremia and recurrent arthritis caused by Streptococcus pyogenes in a heroin addict with AIDS]. AB - BACKGROUND: Streptococcus pyogenes is a bacteria which, at present, is seldom isolated in blood and articular fluid. An intravenous drug addict with human immunodeficiency virus infection, with bacteremia and arthritis by S. pyogenes, associated with tuberculosis is presented. METHODS: Blood and articular fluid cultures were collected in the usual and Lowenstein-Jensen media. RESULTS: The patient improved with penicillin and tuberculostatic drugs. Nine months after this episode, the patient reinitiated intravenous drug addiction, and developed another presentation of bacteremia and arthritis by S. pyogenes. CONCLUSIONS: Heroin addict patients constitute a risk group for bacteremias ans severe infections by S. pyogenes. PMID- 7981291 TI - [Tricuspid endocarditis caused by penicillin-resistant Staphylococcus aureus: 2 cases in parenteral drug addicts]. AB - BACKGROUND: Staphylococcus aureus is the main causal agent of infectious endocarditis (IE) in intravenous drug addicts (IVDA) with most of the strains, isolated in Spain being resistant to penicillin and sensitive to methycillin, although the latter condition varied in recent years. Two cases of IE caused by S. aureus strains sensitive to penicillin in IVDA are presented. METHODS: All bacteremia episodes diagnosed in the Hospital General Penitenciario (Madrid) over a 33-month period (March 1991 to December 1993) were prospectively studied. Special attention was given to patients diagnosed of IE. Blood cultures were processed according to the usual technique by a non radiometric system. RESULTS: One hundred and four bacteremias were detected with 14 being produced by S. aureus. Ten episodes of the total number of bacteremias fulfilled criteria for IE with 2 being produced by strains of S. aureus sensitive to penicillin (CMI < 0.06 mu/ml). Both patients had coinfection by HIV. The clinical evolution prior to diagnosis was prolonged although clinical and microbiologic cure were achieved with intravenous beta-lactam antibiotics treatment, without complications. CONCLUSIONS: Despite the low incidence of the isolation of Staphylococcus aureus sensitive to penicillin (< 3%) recently observed in Spain, strains producing severe infections, showing patterns of sensitivity such as those found during the preantibiotic era, may still be isolated. PMID- 7981292 TI - [The AIDS patient of the 90s (I)]. PMID- 7981293 TI - [Cerebral abscess and HIV infection]. PMID- 7981294 TI - [Cutaneous exanthema in patient with acute lymphoblastic leukemia]. PMID- 7981295 TI - [Haemophilus aphrophilus bacteremia and diagnostic criteria of infectious endocarditis]. PMID- 7981296 TI - [Pneumonitis as an unusual complication of measles and chickenpox]. PMID- 7981297 TI - [Long-course fever and recurrent exanthema as manifestations of Corynebacterium sp. endocarditis]. PMID- 7981298 TI - [Antibiotic sensitivity of beta-hemolytic streptococcus group A]. PMID- 7981299 TI - [Visceral leishmaniasis with intestinal involvement in a patient with AIDS]. PMID- 7981300 TI - [Bacterial endophthalmitis caused by Klebsiella pneumoniae associated with urinary sepsis]. PMID- 7981302 TI - [Pneumonia caused by varicella]. PMID- 7981301 TI - [Tuberculous chylothorax]. PMID- 7981303 TI - [Bacteremial pneumonia caused by Moraxella catarrhalis in a neutropenic patient]. PMID- 7981304 TI - Was it just stupid or are we poor educators? PMID- 7981305 TI - Prospects for the use of adeno-associated virus as a vector for human gene therapy. PMID- 7981306 TI - Factors influencing retroviral-mediated gene transfer into hepatocytes in vivo. AB - Direct gene transfer into hepatocytes represents an attractive alternative to organ transplantation for the treatment of genetic liver diseases. This approach is hampered either by the difficulty to obtain, cultivate, and reimplant hepatocytes or by the poor stability of the expression of the transgene. In the present report, we show that direct in vivo infection of hepatocytes with a retroviral vector following partial hepatectomy results in a life-long expression of the transgene in adult rats and mice. We demonstrate that the kinetics of hepatocyte susceptibility to infection is closely associated with the kinetics of cell division. We also present evidence that a complete vascular exclusion of the organ allows better gene transfer as compared to simple portal infusion of the viral particles, presumably through a higher volume of retrovirus-containing medium delivered to the liver. PMID- 7981307 TI - In vivo delivery of interleukin-4 by a recombinant vaccinia virus prevents tumor development in mice. AB - To study the immunotherapeutic potential of interleukin-4 (IL-4) delivered in vivo via a recombinant vaccinia virus, a thymidine kinase-negative (TK-) vaccinia virus that expressed the murine IL-4 gene (VV1/IL-4) was constructed. When mice were inoculated with 10(7) plaque-forming units (pfu) of VV1/IL-4 subcutaneously (s.c.), 10(5) pfu/cm2 were found in skin, and smaller numbers in liver and kidney between 1 and 7 days after infection; few viral pfu were found in spleen and lung, or in any organ after intravenous infection. This suggested that recombinant vaccinia viruses might be most efficient at delivery of cytokine genes to the skin. Because IL-4 has recently been found to have potent anti-tumor activity, the effect of recombinant virus infection on the development of s.c. tumors was studied. A single s.c. inoculation with VV1/IL-4 delayed the development of NCTC 2472 tumors, but when VV1/IL-4 was inoculated s.c. weekly for 8 weeks, tumor development was completely prevented in 93% of mice. Similarly, the development of M-3 melanoma tumors was also prevented by weekly s.c. inoculations of VV1/IL-4. About 40% of mice treated with control VV2/beta gal by the same regimen also failed to develop tumors. Weekly virus treatment did not prevent NCTC 2472 tumor development in athymic nu/nu mice, suggesting that mature T cells are required for expression of VV1/IL-4 induced antitumor activity. Thus, recombinant vaccinia viruses may be especially well suited for convenient therapeutic delivery of immunomodulator genes to skin-related sites. PMID- 7981308 TI - In vivo gene transfer into rabbit thyroid follicular cells by direct DNA injection. AB - Direct injection of DNA expression vectors into muscle leads to expression of encoded recombinant gene products in mature muscle cells. This phenomenon is not shared by most other organs. We have surveyed various organs in the rabbit to identify other cell types that would express DNA vectors after direct injection. We observed that thyroid follicular cells were capable of acquiring plasmid DNA and expressing recombinant gene products after direct interstitial injection of plasmid vectors into the thyroid gland. The level of expression of a chloramphenicol acetyltransferase (CAT) reporter gene in thyroid tissue was similar to that seen in muscle tissue three days after injection in controlled experiments. Using a beta-galactosidase reporter gene, expression was localized to thyroid follicular cells. CAT activity decreased with first-order kinetics and a half-life t1/2 of 40 hr. DNA was identified in thyroid tissue by polymerase chain reaction (PCR) analysis and displayed first-order elimination kinetics with a half-life t1/2 of 10 hr. The persistence of the gene and gene product in the thyroid was significantly different from that observed after injection of DNA vectors into muscle or delivery of DNA vectors to the liver using asialoglycoprotein/polylysine/DNA complexes, suggesting that there are significant differences in the process of DNA uptake or compartmentalization in these experimental systems. These results introduce the possibility of developing the thyroid as a novel target for treating certain thyroid or systemic diseases using DNA vectors. PMID- 7981309 TI - Retroviral delivery of DNA into the livers of transgenic mice bearing premalignant and malignant hepatocellular carcinomas. AB - To develop gene therapy for hepatocellular carcinoma (HCC), we infused mice through the portal vein with retrovirus carrying the Escherichia coli beta galactosidase reporter gene under the transcriptional control of the viral long terminal repeat (LTR) and the promoter from the mouse multidrug resistance gene mdr1b. Two transgenic mouse HCC models were used, one bearing the human hepatitis B viral envelope protein and the other SV40 T antigen. These animals develop HCC with predictable pathological manifestations. The viral transduction efficiency appeared to depend upon the stage of the disease in the animals. The most efficient transduction occurred when the livers had developed microscopic nodular hyperplasia; in some cases as many as 0.01-0.1 copies/cell were transduced. The transduction efficiency was lower in the late stage of the disease when livers had a heavy tumor burden and in the early stage when no lesion was evident. Low viral transduction efficacy was also seen in nontransgenic animals but was significantly increased by partial hepatectomy. The expression of the reporter gene in these animals was very low, as determined by histological staining. These results suggest that hepatocarcinogenesis can enhance retroviral delivery of foreign genes into the liver. Further development by increasing the viral transducing efficiency and the level of expression of transduced gene is required. PMID- 7981310 TI - Cytotoxic T lymphocyte and antibody responses generated in rhesus monkeys immunized with retroviral vector-transduced fibroblasts expressing human immunodeficiency virus type-1 IIIB ENV/REV proteins. AB - The immune response against human immunodeficiency virus type-1 (HIV-1) is believed to play a role in controlling the early stages of disease progression. The cellular immune response, in particular cytotoxic T lymphocyte (CTL) activity, may be important for eliminating virally infected cells in HIV-1 infected individuals. Genetic immunization using retroviral vectors provides an effective means of introducing antigens into the antigen presentation pathways for T cell stimulation. A nonreplicating, amphotropic murine retroviral vector containing the HIV-1 IIIB env gene has been used to transduce primary rhesus monkey fibroblasts for the expression of HIV-1 antigenic determinants. Rhesus monkeys were immunized with four doses of either vector-transduced autologous fibroblasts (VTAF) expressing the HIV-1 IIIB ENV/REV proteins or nontransduced autologous fibroblasts (NTAF) administered at 2-week intervals. The animals were evaluated for both the induction of HIV-1-specific immune responses and potential toxicity associated with this ex vivo treatment. The VTAF-immunized monkeys generated CTL responses specific for HIV-1 ENV/REV expressing autologous target cells, whereas, NTAF-immunized monkeys showed negligible CTL activity. The cytotoxic activity was mediated by CD8+, major histocompatibility complex (MHC) restricted CTL. In addition, antibody responses directed against the HIV-1 gp120 protein were also detected in the sera of VTAF-immunized monkeys. Clinical and histopathological evaluation of immunized monkeys showed no evidence of significant adverse events. Several animals that received either VTAF or NTAF had detectable anti-cytoplasmic antibodies, but were not positive for anti-nuclear antibodies or rheumatoid factor. Subsequent evaluation of renal, synovial, and hepatic tissue samples from these monkeys revealed no autoimmune disease associated lesions. This study demonstrates the safety and ability of autologous retroviral vector-transduced cells expressing HIV-1 IIIB ENV/REV proteins to stimulate immune responses in a non-human primate model, and provides a basis for this form of genetic immunization in HIV-infected humans. PMID- 7981311 TI - Gene therapy for the treatment of recurrent pediatric malignant astrocytomas with in vivo tumor transduction with the herpes simplex thymidine kinase gene/ganciclovir system. PMID- 7981312 TI - Captopril and its probable contaminants: NMR and MS features of analytical value. AB - The 400 MHz 1H NMR spectrum of captopril in a variety of solvents is analysed and compared with those of epicaptopril and its disulphide analogue. A method for detecting isomeric and oxidative impurities by examination of a 1H NMR spectrum of captopril in DMSO-d6 is proposed. 13C NMR and MS data enable differentiation of captopril from its disulphide analogue but not from its diastereoisomer epicaptopril. PMID- 7981313 TI - The assessment of the HO. scavenging action of therapeutic agents. AB - A new method is reported for the assessment of the HO. scavenging action of therapeutic agents. It is based on the photolysis of zinc oxide and has a detection limit of 3.3%. The scavenging order of the compounds tested was penicillamine > rentiapril > ascorbic acid > cysteine > glutathione > thiomalic acid > N-acetylcysteine > myocrysin > methionine. None were as effective as DMSO. It is argued that these compounds can have an in vivo protective effect where HO. is produced from oxidant producing cells, thus limiting radical induced damage. PMID- 7981314 TI - Statistical evaluation of molecular descriptors and quantitative structure property relationship studies of retinoids. AB - Various molecular descriptors, including connectivity indices, sums of the intrinsic state values, electrotopological state indices, topological equivalence indices, kappa indices, normalized Bonchev-Trinajstic and Shannon information indices, Wiener and Platt's F numbers and molecular weight, were calculated for 73 retinoids, whose structures and properties were taken from the literature. A novel methodology using statistical analyses (cluster, factor and stepwise regression) in selecting relevant molecular descriptors for quantitative structure-property relationship (QSPR) studies has been developed. The analyses were used in correlating molecular structure with affinity, pharmacokinetic properties and reversed-phase retention of retinoids. PMID- 7981315 TI - Spectrofluorimetric analysis of cefuroxime in pharmaceutical dosage forms. AB - A fluorimetric method has been developed for the quantitative analysis of cefuroxime, based upon the formation of a fluorescent derivative formed by alkaline hydrolysis with 1.0 M sodium hydroxide and heating at 100 degrees C for 60 min. The fluorescent product gave excitation and emission maxima at 380 and 436 nm, respectively. The method was performed in aqueous solution adjusted to pH 10.5 by addition of phosphate buffer solution. The calibration curve was found to be linear in the range of concentrations 0.050-1.70 micrograms ml-1. The lower limit of detection was 1.0 x 10(-2) micrograms ml-1. The method was applied to authentic pharmaceutical preparations containing cefuroxime sodium or cefuroxime axetil, the 1-(acetyloxy) ethyl ester of the drug, and was found to be satisfactory. Cefuroxime sodium was also determined in physiological solutions used to prepare intravenous infusions of this antibiotic. PMID- 7981316 TI - Joint determination of todralazine and acetazolamide in human serum by differential pulse polarography. AB - Differential pulse polarography (DPP) is proposed as a direct method for the quantitation of todralazine and acetazolamide in human serum. The method was applied to the determination of these drugs in human serum, after a liquid-liquid extraction process. This extraction process together with the use of the standard additions method is essential for the elimination of the matrix effect. The proposed method enables detection limits of 0.107 microgram ml-1 for acetazolamide and 0.111 microgram ml-1 for todralazine to be achieved at reduction potentials of -0.59 and -0.86 V, respectively, using Britton-Robinson buffer (pH 1.65) as the supporting electrolyte. PMID- 7981317 TI - Solid state investigation of mefloquine hydrochloride. AB - Mefloquine hydrochloride was crystallized under different conditions and the products were studied by thermal analysis, IR spectroscopy and X-ray diffraction. It was demonstrated that different conditions of crystallization resulted in different crystal structures. The alpha- and delta-modifications were hydrates, the beta- and gamma-forms were polymorphs, the epsilon-form was an acetone solvate and theta-mefloquine was tetrahydrofuran solvate. During long storage at room temperature, the alpha-, delta- and theta-forms of mefloquine hydrochloride were transformed. By heat treatment of the delta-, epsilon and theta modifications, a new crystal structure was obtained. PMID- 7981318 TI - An enzymatic assay for the MAO-B inhibitor selegiline in plasma. AB - A sensitive fluorimetric assay based on inhibition of rat brain monoamine oxidase B (MAO-B) in vitro has been described. The procedure measures the inhibition of MAO activity produced by the addition of selegiline extracted from human plasma. This method uses the substrate kynuramine which is converted by MAO to the product 4-hydroxyquinoline which fluoresces in alkaline solution. Human plasma (500 microliters) containing different concentrations of selegiline was deproteinized and extracted with ethyl acetate-butyl chloride. After reconstitution with 200 microliters phosphate buffer, 50 microliters of rat brain homogenate was added to study the MAO-B inhibition. Selegiline metabolites, amphetamine and methamphetamine (50 ng ml-1), and desmethylselegiline (20 ng ml 1), showed no inhibitory effect on MAO-B inhibition. Selegiline concentrations as low as 0.25 ng ml-1 can be detected. The standard curve was linear from 125 pg (0.25 ng ml-1) to 4000 pg (8.0 ng ml-1) in the incubation tube. This method should be helpful to determine pharmacokinetic parameters of selegiline after i.v. or oral dosing. PMID- 7981319 TI - Separation of 2-arylpropionic acids on a cellulose based chiral stationary phase by RP-HPLC. AB - The enantiomers of eight 2-arylpropionic acids, a group of chiral non steroidal antiinflammatory drugs, were resolved as their benzylamide derivatives on a high performance liquid chromatographic chiral stationary phase consisting of a covalently bound tris (4-methylbenzoate) cellulose layer on silica gel. The column was used under reversed-phase conditions using methanol as the main mobile phase component, with a perchlorate buffer pH 2.0. A compromise for derivatization with a water soluble carbodiimide and 1-hydroxybenzotriazole of a group of eight analytes was obtained. The derivatives were identified by IR- and MS-spectroscopy. PMID- 7981320 TI - Enantiomeric separation of amide derivatives of some 2-arylpropionic acids by HPLC on a cellulose-based chiral stationary phase. AB - A reversed phase high-performance liquid chromatographic method has been developed for the determination of the R- and S-enantiomers of ibuprofen, flurbiprofen, ketoprofen and tiaprofenic acid. Separation has been achieved using a tris(4-methylbenzoate)cellulose phase after derivatization into their amides. Flurbiprofen could also be partially resolved into its enantiomers without prior derivatization. PMID- 7981321 TI - First-derivative UV spectrophotometric and high-performance liquid chromatographic analysis of some thiazide diuretics in the presence of their photodecomposition products. AB - Ethanolic solutions of three thiazide diuretics, chlorothiazide, hydrochlorothiazide and trichlormethiazide, were irradiated with a high-pressure mercury lamp. The products were isolated and their first-derivative UV spectra in ethanol were recorded and compared to those of the parent compounds. The determination of the parent compounds in the presence of the decomposition products was carried out at wavelengths near 220 nm using the zero-crossing technique. Three reversed-phase HPLC methods were also developed for the analysis of the parent compounds. In parallel analyses of the reaction mixtures a good correlation was achieved between these two methods in the determination of hydrochlorothiazide and trichlormethiazide while there was greater variation in the results of chlorothiazide. PMID- 7981322 TI - HPLC determination of 1,2-diethyl-3-hydroxypyridin-4-one (CP94), its iron complex [Fe(III) (CP94)3] and glucuronide conjugate [CP94-GLUC] in serum and urine of thalassaemic patients. AB - Sensitive and selective high performance liquid chromatographic (HPLC) methods for the quantification of 1,2-diethyl-3-hydroxypyridin-4-one (CP94), its iron complex [Fe(III) (CP94)3] and glucuronide metabolite (CP94-GLUC) in urine and serum of thalassaemic patients are described. Three separate analyses are involved. The first assay quantifies both CP94 and its iron complex. This procedure requires the conversion of the iron complex to the free ligand and is carried out using diethylenetriaminepentaacetic acid (DTPA). CP94 and the internal standard, 1-propyl-2-ethyl-3-hydroxypyridin-4-one (CP95) present in either serum or urine are then extracted at pH 7.0 with dichloromethane. Extraction efficiency is 96.0 +/- 5.6% and 100 +/- 7.1% for CP94 and CP95, respectively, and 31.2 +/- 2.1% at 30 microM and 53.2 +/- 4.2% at 300 microM for the corresponding iron complex. In the second assay, samples are incubated (16 h) with beta-glucuronidase and processed as before. In this assay, the drug, its iron complex and glucuronide conjugate are measured. In the third assay the iron complex of CP94, [Fe(III) (CP94)3] is quantified. From the three separate analyses it is possible to calculate the individual concentrations of the three separate components present in serum and urine of thalassaemic patients. Calibration for both components, i.e. CP94 (assays 1 and 2) and its iron complex (assay 3) are linear with correlation coefficients > 0.99 and are reproducible over the required concentration range of 0-500 microM for the free ligand and 0 100 microM for the iron complex. The minimum quantifiable level is 0.5 microM for the free ligand and 1.0 microM for the iron complex. PMID- 7981323 TI - Determination of flunitrazepam in plasma by liquid chromatography. AB - A reversed-phase liquid chromatographic method has been used to determine flunitrazepam in plasma. Extraction was simple and there was no need to hydrolyse the drug. Separation was achieved on a 150 x 3.9 mm i.d. column packed with 4 microns Nova Pack C18 using a mobile phase of water-acetonitrile-triethylamine (700:300:4, v/v/v) (adjusted to pH 7.5 with orthophosphoric acid). The method was shown to be rapid and reliable with a lower limit of detection of 5 ng ml-1. Results are reported of simple experiments on the effects of temperature and light on the stability of flunitrazepam in plasma kept on the laboratory bench. PMID- 7981324 TI - A reversed-phase high-performance liquid chromatographic method for the determination of Clanfenur in rat and human plasma. AB - A selective and specific high-pressure liquid chromatographic (HPLC) method for the simultaneous assay of Clanfenur and its metabolites in biological fluids of interest has been developed which is suitable for routine analysis, using micro volumes (0.1 ml) of plasma samples only. After protein precipitation the extract is analysed by reversed-phase HPLC with UV detection. Excellent recovery, linearity, accuracy and precision (less than 5% for plasma) are achieved by the assay which is able to quantify Clanfenur and its metabolites in plasma at concentrations between 0.025 and 5.0 mg l-1. PMID- 7981325 TI - Determination of m-hydroxymandelic acid, m-hydroxyphenylglycol and their conjugates in human plasma using liquid chromatography with electrochemical detection. AB - An LC method for the analysis of m-hydroxymandelic acid (MHMA) and m hydroxyphenylglycol (MHPG) and their conjugates in human plasma was developed and validated. The method for the quantitation involved extraction of acidified plasma (subject to hydrolysis with beta-glucuronidase for 120 min with 500 units of enzyme/0.25 ml of plasma at 37 degrees C for the conjugates) with an organic phase (methyl-tert-butyl ether). Analysis of MHMA, MHPG and the internal standard (3-hydroxy-4-methoxymandelic acid) was carried out on an ODS stationary phase: 100 x 4.6 mm, 5 mu followed by a 75 x 4.6 mm, 3 mu using 1% acetonitrile in 0.1 M acetic acid as the mobile phase. An electrochemical detector operated at +1.15 V vs Ag/AgCl was employed for the detection. The standard curves were linear in the range of 10.0-250.0 ng ml-1 for MHMA and 5.0-125.0 ng ml-1 for MHPG. The limit of quantitation was 10.0 ng ml-1 for MHMA and MHPG. Acceptable accuracy and precision were obtained during the intra-batch and inter-batch analysis for both the assays. PMID- 7981326 TI - Use of isosbestic points of derivative absorption curves: the dissolution rate determination of aspirin. PMID- 7981327 TI - Colorimetric determination of prenalterol hydrochloride in dosage forms. PMID- 7981328 TI - Tissue kallikrein activity and kinin release in human endothelial cells. AB - The kininogenase, tissue kallikrein (EC 3.4.21.8), has been identified in different blood vessels. The enzyme was mainly found in vascular smooth muscle cells. It is not known whether it is present and functionally active in vascular endothelial cells. The following study investigates the presence of tissue kallikrein in endothelial cells from human umbilical veins and pulmonary arteries. Tissue kallikrein was demonstrated in three ways: 1) by immunostaining in endothelial cells; 2) by measurement of tissue kallikrein activity using a colorimetric assay; 3) by the measurement of kinin release in intact and homogenised endothelial cells with a radioimmunoassay. Immunostaining demonstrated the presence of tissue kallikrein in endothelial cells from human umbilical veins and endothelial cells from human pulmonary arteries. Tissue kallikrein-like activity, measured by the degradation of D-Val-cyclohexyl-Ala-Arg 4-nitraniline, was 3.57 +/- 0.5 mU/10(6) endothelial cells from human umbilical veins and 7.52 +/- 0.84 mU/10(6) endothelial cells from human pulmonary arteries. Intracellular kinin concentrations were 424 +/- 83 pg/10(6) cells in endothelial cells from human umbilical veins and 576 +/- 146 pg/10(6) cells in endothelial cells from human pulmonary arteries, and they increased in a time-dependent manner after homogenisation. The increase was abolished by aprotinin (1000 kIU), an inhibitor of tissue kallikrein in both cell types. Addition of exogenous kallikrein (5 mU) to homogenised cells led to a five fold increase of kinin concentrations after five minutes, indicating a sufficient resource of cellular kininogen. Removal of extracellularly bound kininogen by washing with dextran sulphate (100 mg/l) resulted in an approximately 75% reduction of the cellular kinin release.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7981329 TI - Lipoamidase and biotinidase activities in the rat: tissue distribution and intracellular localization. AB - Lipoamidase (not yet given an EC number) activity was measured in various rat tissues using two different substrates, one natural, lipoyllysine (epsilon-N-(D,L lipoyl)L-lysine) and one artificial, lipoyl-p-aminobenzoic acid (N-D,L-lipoyl-p aminobenzoic acid). Biotinidase, EC 3.5.1.12, was measured in the same tissue with the artificial substrate, biotinyl-p-aminobenzoic acid (N-D-biotinyl-p aminobenzoic acid). Lipoamidase measured as lipoyl-p-aminobenzoic acid hydrolase activity had two pH optima, at pH 6.0 and pH 9.5, in liver homogenate, but only one pH optimum at pH 6.0 in rat plasma. Lipoamidase measured as lipoyllysine hydrolase activity had a pH optimum at pH 5.5 both in liver homogenate and plasma. Similarly, biotinidase shows a single pH optimum at pH 6.0 in liver homogenate and plasma. The properties of lipoyllysine hydrolase and biotinidase were similar with respect to thermostability, pH stability and inhibition pattern, and their properties differed from those of lipoyl-p-aminobenzoic acid hydrolase. Lipoyllysine hydrolase and biotinidase activities were highest in kidney, liver and blood plasma, whereas lipoyl-p-aminobenzoic acid hydrolase activities were highest in liver, brain and kidney. Lipoyllysine hydrolase and biotinidase activities were found mainly in the liver microsomal fraction, and lipoyl-p-aminobenzoic acid hydrolase was recovered from the microsomal fraction and to a small extent from the mitochondrial fraction. These results indicate that liver lipoyl-p-aminobenzoic acid hydrolase is an enzyme protein which differs from lipoyllysine hydrolase, and the data also indicate that liver lipoyllysine hydrolase and biotinidase are the same enzyme protein. PMID- 7981330 TI - Prognostic significance of autoantibodies to laminin in the sera of breast cancer patients: a preliminary report. AB - Interactions between cancer cells and laminin play an important role in the metastatic cascade. The aim of this retrospective study was to evaluate the presence and the prognostic significance of autoantibodies to laminin in sera of patients with breast cancer. Our study population consisted of 71 high-risk primary breast cancer patients (median follow-up, 6 years). IgG, IgA and IgM were analysed at the time of surgery and before any treatment was given. Concentrations were measured by enzyme immunoassay with a highly purified antigen. IgG, IgA and IgM anti-laminin median values were, respectively 117%, 130% and 97% of normal absorbance. Higher concentrations of IgM to laminin were found in pre-menopausal patients as compared with post-menopausal patients (p < 0.001). Patients with high concentrations of IgG to laminin had lower disease free (p = 0.003) and overall survival rates (p = 0.003). In breast cancer, assay of IgG to laminin could thus provide a cheap and easy prognostic index available for all patients. PMID- 7981331 TI - Interference in clinical laboratory tests, with special regard to the bilirubin assay: effects of a metabolite of the new prolyl 4-hydroxylase inhibitor, Lufironil. AB - During the toxicological examination of the fibrosuppressive agent, Lufironil (INN), in rats a dose-dependent positive reaction for urinary bilirubin was observed. This positive reaction was found in quantitative assays, and when using test strips. The positive reaction for bilirubin in these assay systems was caused by a metabolite of Lufironil. It was not due to drug toxicity, and it was not caused by any endogenous substrate produced under the influence of Lufironil. The compound responsible for this reaction was isolated by HPLC and its structure determined by spectroscopic methods. The structure was confirmed by synthesis, starting from pyridine-2,4-dicarboxylate. The synthesized compound and the compound in urine gave an identical reaction with the test reagent for bilirubin. PMID- 7981332 TI - Diagnostic value of lactoferrin analysis in pleural effusions. AB - Lactoferrin was analysed with an ELISA in pleural effusions from 21 patients with malignant exudative effusions (15 carcinomas and 6 mesotheliomas), 12 patients with non-malignant exudative effusions of unknown aetiology, 11 patients with transudative effusions due to congestive heart failure, 12 patients with exudative effusions secondary to infection, and 2 patients with tuberculous effusions. Median pleural fluid lactoferrin was 133 micrograms/l (range 25-435) in carcinomas, 55 micrograms/l (23-185) in mesotheliomas, 198 micrograms/l (31 530) in non-malignant exudates, 68 micrograms/l (17-205) in transudates, 1815 micrograms/l (1380-2050) in infectious exudates and 107 micrograms/l (88-125) in tuberculosis. Due to a wide overlap between the various groups pleural fluid lactoferrin appears to be of limited value in the routine diagnostic evaluation of non-infectious pleural effusions, but seems to separate infectious exudates from non-infectious exudates. PMID- 7981333 TI - Phenylketonuria screening with a fluorometric microplate assay. AB - A fluorometric assay in microtitre plates for the screening of phenylketonuria was evaluated and adapted to a neonatal screening programme. Using this assay, it is possible to determine quantitatively the phenylalanine concentration in dried blood spots on filter paper. The test exhibited a linear calibration curve with a good slope as well as sufficient precision and accuracy in the statistical analysis. Interference by other amino acids and antibiotics was not observed. Only elevated concentrations of leucine interfered to a small degree. The phenylalanine concentration in dried blood spots of 13 phenylketonuria patients correlated to that in serum. 7381 dried blood samples of newborn infants were tested simultaneously by both the fluorometric and the Guthrie test. The results did not show significant differences. We screened 29,182 newborns using the fluorometric assay and an online data processing programme. The internal repetition rate was 0.64%, the external recall rate 0.15%. False negative results were not observed. In December 1991 the fluorometric method replaced the Guthrie test in our routine programme for phenylketonuria screening, and was introduced as a follow up test for phenylketonuria patients. PMID- 7981334 TI - Improvements in creatinine methodology: a critical assessment. AB - A large evaluation study, analytical as well as clinical, was performed on four published improvements for the determination of creatinine in serum. Two of the methods were based on the Jaffe reaction, the other two were enzymatic methods. Analytically, all four methods showed a similar performance. In the analysis of numerous specimens from advanced care departments, however, the methods performed differently. The two enzymatic procedures scored better than the two Jaffe methods, when compared with an HPLC-based reference method. However, even the best methods produced outliers and a larger scatter than that obtained with "normal" specimens. PMID- 7981335 TI - Comparison of the determination of magnesium by methylthymol blue spectrophotometry and atomic absorption spectrophotometry. AB - Plasma samples (n = 155) of 30 patients on an intensive ward were analysed for magnesium simultaneously by atomic absorption spectrophotometry (AAS) and methylthymol blue spectrophotometry. Methylthymol blue spectrophotometry was performed at the bedside, using two different multianalysers, Easy ST 1 and Easy ST 2, Merck, D-Darmstadt. Precision was 12.2% (Easy ST 1) and 17.1% (Easy ST 2), and the average value was 0.89 mmol/l, which was above the expected range (0.72 0.88 mmol/l). Accuracy was 16.25% (Easy ST 1) and 8.75% (Easy ST 2). Analyser 2 was more accurate (8.75% versus 6.25%) but less precise (17.1% versus 12.2%) than analyser 1. Precision of AAS was between the expected values of 0.69 and 0.84 mmol/l. Easy ST and AAS gave significantly different values (p < 0.0001) for 155 measurements. Comparison of AAS and methylthymol blue spectrophotometery showed that methylthymol blue spectrophotometry produced higher values than AAS (mean difference 0.186 mmol/l). Furthermore, analyses of 40 samples of a standardized plasma concentration with methylthymol blue spectrophotometry showed a very low precision (15.3%). Easy ST cannot be assigned for urinary measurements of magnesium. Experimentally measured samples gave unaccountable results. PMID- 7981336 TI - Glycogen phosphorylase isoenzyme BB mass release after coronary artery bypass grafting. AB - Glycogen phosphorylase isoenzyme BB mass release was studied in 20 patients undergoing coronary artery bypass grafting. In 16 patients with uneventful coronary artery bypass grafting, glycogen phosphorylase isoenzyme BB mass concentrations showed a significant, transient increase in the post cross clamping period and decreased to baseline values within 20 hours (peak concentrations ranged from 12.7 micrograms/l to 47.5 micrograms/l, median 40 micrograms/l). One patient did not fulfil criteria for perioperative myocardial infarction, but clinical data indicated myocardial injury after aortic unclamping. In this patient only glycogen phosphorylase isoenzyme BB mass concentration and not creatine kinase isoenzyme MB catalytic concentration was increased, compared with uneventful patients. In 2 patients with emergency coronary artery bypass grafting for evolving myocardial infarction, glycogen phosphorylase isoenzyme BB mass concentrations, but not creatine kinase isoenzyme MB catalytic concentrations, correlated with clinical evidence of myocardial ischaemia. Our data indicate that glycogen phosphorylase isoenzyme BB mass concentration is a very sensitive laboratory marker of perioperative myocardial injury in patients undergoing coronary artery bypass grafting. PMID- 7981337 TI - Critical evaluation of fully automated enzyme immunoassays for free thyroxine and thyrotropin. AB - The technical and diagnostic performance of fully automated immunoassays for free thyroxine and thyrotropin using streptavidin/biotin technology (Enzymun-Test) were examined. The between-assay precision for free thyroxine was 10.4%, 5.4%, 2.5%, 2.3%, 1.1%, and 1.8% at 3.02, 6.27, 17.2, 21.9, 25.6, 42.7 pmol/l; and for thyrotropin was 14.2%, 4.7%, 2.9%, 2.8%, 3.2%, 4.5% at 0.12, 0.46, 1.03, 2.05, 4.8, 12.7 mU/l. The functional detection limit of the assay was 0.09 mU/l. Results for the free thyroxine method correlated well with the IMx (r = 0.91) and the equilibrium dialysis (r = 0.95) assay. Results for the thyrotropin method correlated well with the Tandem-TSH (r = 0.99) and the IMx (r = 0.99) assays. The euthyroid reference range was 11-23 pmol/l and 0.5-3.9 mU/l for free thyroxine and thyrotropin respectively. The free thyroxine assay was not influenced by changes in albumin or thyroxine binding globulin concentration but showed increases at oleic acid concentrations > 4 mmol/l. Spuriously elevated free thyroxine concentration were found in 4 patients, due to assay interference by antibodies in the serum. In a follow up study of 46 patients with non-thyroidal illness, serial measurements showed fluctuating free thyroxine and thyrotropin concentrations with abnormal results occurring in 34%. In a hospital setting, a wider range of free thyroxine (10-28 pmol/l) and thyrotropin (0.22-5.9 mU/l) concentration may be observed in patients who are clinically euthyroid. Abnormal thyroid function tests were however transient and follow up resolved most diagnostic problems. PMID- 7981338 TI - Pseudohyperphosphataemia incidence in an automatic analyzer. AB - A routine blood analysis, using the Hitachi 717 analyser, of an asymptomatic patient with multiple myeloma revealed a phosphate concentration of 6.2 mmol/l (reference range 0.8-1.4 mmol/l). There was no clinical or biochemical evidence for secondary hyperphosphataemia. Two additional myeloma patients with a normal renal function were found to have serum phosphate concentrations of 5 and 4.7 mmol/l. Globulin-depleted sera of these patients were found to have phosphate levels within the normal range as assayed by a Hitachi 717. All these patients were found to have normal inorganic phosphate levels when a SMAC autoanalyser was used, thus indicating spurious readings by the Hitachi 717. The incidence of pseudohyperphosphataemia in 298 patients with normal renal function and hyperglobulinaemia was 8%. To test the direct effect of globulin on phosphate analysis by the Hitachi 717, globulin was precipitated from serum of myeloma and non-myeloma patients by ammonium sulphate. The analysed data showed a positive correlation between globulin concentration and the spurious phosphate levels. Furthermore, even when inorganic phosphate was completely removed from the tested samples, spurious phosphate readings were detected in the presence of globulins from either myeloma or non-myeloma patients by Hitachi 717. It can be concluded that the ammonium molybdate method for determining inorganic phosphate in the Hitachi 717 gives spuriously high phosphate levels in the presence of a high serum globulin concentration. PMID- 7981339 TI - Performance of the Coulter STKS and the Sysmex NE-1500 in a paediatric population. AB - The Coulter STKS and the Sysmex NE-1500 were evaluated for their performance in paediatric samples. Special attention was paid to the ability of both instruments to detect white blood cell morphology abnormalities. Therefore a population with a high frequency of pathologies was selected. The studied population included children aged between 1 month and 14 years, 45% of which suffered from oncological and/or haematological diseases. Two hundred and forty blood samples were analysed. The leukocyte differentiation results from the Coulter STKS and the Sysmex NE-1500 were compared with the manual microscopic method. The differentials compared very well for neutrophils, lymphocytes and eosinophils. Sensitivity and specificity for the detection of blasts, immature granulocytes, left shift and atypical lymphocytes were examined. While specific morphology flagging showed a rather low sensitivity, blasts and immature granulocytes were mostly detected by the two systems, taking into account white blood cell alarm flags other than the two mentioned above. The overall sensitivity for the detection of white blood cell abnormalities was better with the Coulter STKS, whereas the Sysmex NE-1500 showed a higher specificity. In an ancillary study which was performed exclusively on neonatal samples, of which 80% originated from preterm infants, we found a limited sensitivity for the detection of low percentages of nucleated red blood cells for both analysers. The high frequency of abnormalities, together with the limited sensitivity mentioned above, prompted us to review all neonatal samples in the future. PMID- 7981340 TI - Ascorbic acid in porcine transplanted liver and small bowel. PMID- 7981341 TI - [Protection for the heart and brain: anesthesia in carotid artery operations]. PMID- 7981342 TI - [Anesthesia in carotid surgery]. AB - Carotid endarterectomy has become a standard surgical procedure in the therapy of cerebrovascular insufficiency. An important consideration in this form of therapy is to maintain a low perioperative morbidity and mortality. In planning the procedure the two most frequent complications deserve special consideration. Thromboembolism is the major cause of new neurological deficits and prevention should be emphasized as therapeutic interventions are of limited value. The cardiovascular status needs special attention, since the long-term prognosis is predominantly influenced by concomitant coronary artery disease. Regional anaesthesia provides good cardiovascular stability and the chance to monitor neurological changes in an awake patient. Patient discomfort and limited control of vital functions are obviated by general anaesthesia raising the challenge of maintaining cardiovascular stability and establishing adequate cerebral monitoring. Both electroencephalography and somatosensory evoked potentials monitor cerebral function continuously and enable detection of cerebral ischaemia secondary to inadequate blood flow. Another continuous technique is transcranial Doppler sonography; this, however, does not monitor brain function and its role in carotid surgery is still under investigation. Carotid stump pressure or cerebral blood flow measurements provide intermittent data and should therefore only be used as an adjunct. The goal to find an approach that minimizes the risk for the individual patient can only be attained by close cooperation between anaesthesiologists and surgeons. PMID- 7981343 TI - [Swelling and damage to nerves and glial cells by acidosis]. AB - OBJECTIVE: Development of acidosis is a prominent pathophysiological factor in acute cerebral disorders, such as ischaemia or severe brain trauma. The impairment of the acid-base state in brain parenchyma among others is involved in the development of brain oedema, eventually leading to irreversible damage of neurons and glial cells. In the present study the pathophysiological role of acidosis for cytotoxic cell swelling and damage of glial and neuronal cells was investigated in vitro under conditions found in the ischaemic penumbra in vivo- the still viable perifocal border zone surrounding an infarct with elevated interstitial K(+)- and H(+)-concentrations. Assessment of cell swelling by acidosis was combined with experiments on underlying mechanisms as a basis for therapeutical interventions to inhibit cytotoxic brain oedema in vivo. METHODS: C6 glioma cells, astrocytes from primary culture, as well as Neuro-2A cells were cultivated, harvested and suspended as single cells under continuous control of pH, pO2, and temperature according to a standard procedure. Cell volume and cell viability were quantified by flow cytometry. Acidosis was induced by isotonic sulfuric- or lactic acid, respectively. RESULTS: Acidification of the medium led to cell swelling once pH fell below 7.0. Cell viability, however, was not affected by the increasing acidosis down to pH 6.2, while pH 5.6 or below was associated with cell death dependent on the duration of exposure. Acidosis induced cell swelling was attenuated or completely inhibited by blocking of ion exchange mechanisms, such as the Na+/H(+)-antiporter, or elimination of Na+ ions from the medium. CONCLUSION: The present results provide new information on the nature of cytotoxic cell swelling and damage in central nervous system by acidosis under consideration of underlying mechanisms. Accordingly, acidosis induced cell swelling is attributable to activation of ion exchange mechanisms, such as the Na+/H(+)- and Cl-/HCO3(-)-antiporter, in order to maintain a normal cellular acid-base state. This compensation process, however, is associated with the loss of cell volume control by net uptake of osmotic active solutes. Consequently, cell swelling occurring under these conditions is a result of regulatory mechanisms to defend homoeostasis rather than a consequence of cytotoxic cell damage. If cell swelling is inhibited by appropriate treatment, care should be exercised not to enhance the vulnerability of the nerve and glial cells. PMID- 7981345 TI - [Intrapulmonary oxygen storage]. PMID- 7981344 TI - [The value of mini-tracheotomy as a new interventional technique in treatment of postoperative tracheobronchial retention of secretions. Results of a prospective study of 152 surgical intensive care patients]. AB - OBJECTIVE: Since minitracheotomy has been established in 1984 for prophylaxis and therapy of postoperative sputum retention, numerous publications represent technical descriptions, case reports or empirical results, but only few specific facts related to this method have been investigated. In this study we review the efficiency, complications and late follow-up results of minitracheotomy in a department of general surgery. DESIGN: Between 1987 and 1991 we prospectively included 152 intensive-care patients who received minitracheotomy. The average follow-up was 24.2 +/- 6.1 (4-50) months. RESULTS: Endotracheal secretion could be sucked off significantly more often after mini-tracheotomy. The rate of endotracheal suction increased from 5.9 +/- 4.5/d to 18.4 +/- 6.1/d (p < or = 0.01). The pulmonary gas exchange improved at the same time. PaO2 level of 78.9 +/- 9.9 mmHg that decreased to critical values of 60.7 +/- 8.9 mmHg, rose after minitracheotomy above the original levels. Although the PaCO2 level remained constant, a compensatory hyperventilation with a rate of 27.3 +/- 6.9/min was normalised by minitracheotomy. Furthermore, the various methods of minitracheotomy were opposed in this study. In the group of minitracheotomy by cricothyroideal stab incision (n = 55) we recorded 5.4% serious complications. In contrast minitracheotomy by the Seldinger technique (n = 87) could be accomplished without any disturbance. CONCLUSION: Minitracheotomy seems to be an effective and safe treatment for therapy and prophylaxis of postoperative complications due to tracheobronchial sputum retention in critically ill patients. Manipulation was simplified and rendered more safe by the technique of transcutaneous bouginage. PMID- 7981346 TI - The intrapulmonary oxygen store. PMID- 7981347 TI - [Oxygen supply despite respiratory arrest]. PMID- 7981348 TI - [Pre-oxygenation: requirements and reality]. PMID- 7981349 TI - [Effectiveness of the current anesthesia circuit system for pre-oxygenation]. PMID- 7981350 TI - [Special characteristics of pre-oxygenation in children]. PMID- 7981351 TI - [Intrapulmonary O2 storage with the NasOral system]. PMID- 7981352 TI - [Pharmacological brain protection: pro]. PMID- 7981353 TI - [Pharmacological brain protection: contra]. PMID- 7981354 TI - [Failed ideas in anesthesia: Klapp anesthesia with artificially reduced circulation]. PMID- 7981355 TI - [Clinical aspects, analysis and follow-up of poisoning with the alkyl phosphate demeton-S-methylsulfoxide (Metasystox R)]. AB - We report on a 52-year old woman who had taken an unknown dose of the organophosphate insecticide Metasystox R with suicidal intention. Ingestion was followed by cardio-respiratory failure. After successful cardio-pulmonary resuscitation, main therapeutic principles were the immediate application of atropine and decontamination procedures such as gastric lavage, induction of diarrhoea and instillation of carbon. A single combined haemoperfusion and haemodialysis treatment was performed as a secondary elimination technique. After rapid toxicological analysis, obidoxime was administered as a supplementary antidote. After 14 days of treatment, the patient could leave the ICU with a complete restitution. CONCLUSION: Our case report demonstrates the efficiency of immediate application of antidotal therapy (atropine), decontamination and elimination techniques even in case of cardio- respiratory failure after organophosphate poisoning. Toxicological analysis will be beneficial for diagnosis and the indication of further treatment with obidoxime. PMID- 7981356 TI - [Utilization of fibrinolytic agents in complicated parapneumonic effusions]. PMID- 7981357 TI - [Prognostic factors in spontaneous intracerebral hemorrhage]. AB - The introduction of etiological, diagnostic and therapeutical factors have modified the knowledge on the evolutive behaviour of spontaneous intracerebral hemorrhages (ICH). Mortality and morbidity associated to spontaneous ICH were assessed using as independent variables clinical and neuroimage factors obtained upon admission of the patients. We studied 228 patients with spontaneous ICH selected from a data bank of 277 patients with non-traumatic ICH. During the first 24 hours, we assessed several clinical factors (arterial hypertension, Glasgows Neurological Scale and Barthels Scale) and TC images (size, location, extension of bleeding to ventricles, edema and atrophy). Thirty-one per cent of the patients died during the first 2 months. The multiple linear regression study showed that mortality was related to variables of the Glasgows Neurological Scale upon admission, extension to ventricles, size of ICH and perilesional edema, whereas the morbidity was only related to the size of the hemorrhage. Severity of the clinical affection, extension of the bleeding to ventricles, size of the hemorrhage and presence of perilesional edema, but not arterial hypertension, were the main factors affecting mortality at two months of spontaneous ICH. PMID- 7981358 TI - [Influence of pancreatic insulin reserve on the metabolic control of type I and II diabetes mellitus]. AB - We have studied 22 diabetic patients, 14 type I and 8 type II, in order to determine if there is a correlation between metabolic control and pancreatic reserve of insulin. All the patients were treated with optimum doses of bolus/basal insulin. They underwent a peptide C test (at baseline and after 3 stimulus with glucagon) and every month, during 3 months, HbA1c and fructosamine were measured, with monthly self control of glycemia. Both HbA1c and fructosamine showed a statistically significant improvement during the study. In all the cases, there was a negative correlation between metabolic control and pancreatic reserve, with statistical significance for type I, especially regarding the response of peptide C to the administration of glucagon. We conclude that the preservation of a good endogenous secretion of insulin benefits the metabolic control of diabetes. PMID- 7981359 TI - [HIV infection at the Central Military Hospital of Madrid]. AB - We describe the infection by HIV observed in the scope of the Military Hospital and we evaluate the clinical usefulness of the current classification systems. We have retrospectively studied (1986-1993) 80 confirmed cases of infection by HIV: 21 women and 59 men (age range: 17-65 years). Quarterly clinico-biological controls. Initial and final classification according to CDC 87/93 systems. STATISTICAL ANALYSIS: RSIGMA. We have detected in 26% of the patients heterosexual contagion; in 55%, toxicomania and in 17%, homosexuality; 39% had less than 200 CD4/microL upon admission. During the follow-up, 35 patients fulfilled AIDS criteria (17% due to tuberculosis); 17 died (21%) and 30 gave up (37%). CONCLUSIONS: HIV infection is less frequent in the military sociofamiliar environment, with lower incidence of tuberculosis. There is a greater proportion of women, heterosexual transmission and asymptomatic patients. CDC-93 classification is the system best adapted to the natural history of the HIV infection. PMID- 7981360 TI - [Granulomatous hepatitis and fever of unknown origin]. AB - In this paper, we review the etiological, clinical and evolutive aspects of patients with fever of unknown origin (FUO) whose hepatic biopsy showed the presence of granulomas (GH). This is retrospective study covering a period of 10 years (1982-1991). The clinical records of all the patients hospitalized due to FUO (n = 71) and of all those in whose hepatic biopsy the presence of GH (n = 70) was documentated, were reviewed. Thirty patients fulfilled both criteria: FUO + GH. In our environment, Q Fever is the most frequent cause of FUO and GH in patients without infection by the HIV. On the contrary, in patients infected by HIV, the most frequent etiology is tuberculosis. PMID- 7981362 TI - [Favorable response to vinblastine in an idiopathic case of Evans Syndrome]. AB - Evan's Syndrome (ES) may develop in isolation or associated to other autoimmune diseases, solid tumors and lymphoproliferative syndromes. This type of processes can be refractory to the usual medication, that is, to corticoids and splenectomy. High doses of Immunoglobulins (polyvalent IgG) and immunosuppressive drugs are therapeutical alternatives that have been used with different results. We present a case of idiopathic ES refractory to high doses of corticoids and IgG, showing complete remission after the administration of two infusions of vinblastin. We believe that vinblastin is a very useful therapeutical alternative in the cases of ES refractory to the usual treatment. PMID- 7981361 TI - [Spontaneous pneumothorax as the only initial manifestation of bronchogenic carcinoma]. AB - We present the case of a patient with spontaneous pneumothorax associated to pulmonary epidermoid carcinoma, which was not radiologically visible after pulmonary reexpansion. Neither it was macroscopically detected in the first thoracotomy performed for the treatment of the pneumothorax, being diagnosed after the histological study of the resected blisters. The association between pneumothorax and lung cancer is very rare, especially in the absence of other radiological disorders suggesting neoplasia after the pulmonary reexpansion. In these cases, the diagnosis is extremely difficult and it must be always suspected in patients with spontaneous pneumothorax and risk factors for pulmonary cancer. PMID- 7981363 TI - [Pancoast syndrome secondary to small-cell bronchogenic carcinoma. Diagnosis with transbronchial biopsy]. PMID- 7981364 TI - [Congenital deficiency of protein C with late clinical manifestation]. AB - The congenital deficit of protein C has a great diversity of clinical manifestations regarding age. In this paper, we describe the case of a man whose initial symptomatology appeared at the age of 68. Protein C is a vitamin-K dependent plasmatic glycoprotein which has anticoagulant activity through the inactivation of factors Va and VIIIa. The hereditary deficit of protein C is usually presented in a dominant autosomic mode with partial penetration and its prevalence is estimated in each of 200-300 healthy blood donors. PMID- 7981365 TI - [Edema caused by diuretic abuse]. AB - We present the case of an "idiopathic" edema induced by the chronic use of diuretics in a 44-years-old patient. The patient showed a significant secondary hyperaldosteronism which have been erroneousley labelled as primary in previous studies. The pathogenicity of the idiopathic edema and its relation to diuretic abuse are discussed. PMID- 7981366 TI - [Combined strategy of cancerous cells: fat and protein metabolism. Conclusions (3rd of 3 parts)]. AB - The metabolic and biochemical program of neoplastic cells regarding carbohydrate metabolism can be extend to the rest of the metabolism. This gives a rational idea of the global strategy and thermodynamic advantages of malignant cells and of tumors in general as related to the host. A comprehensive, metaenzymatic and transbiochemical approach allows to understand some of the reasons for the limitations found along the last decades by the different chemotherapeutic attempts directed against particular enzymes overexpressed in tumor cells. This indicates that a new vision of the whole problem is preceptive. The overwhelming effects of the hydrogen ion at multiple levels indicates that an initial approach based upon this unifying principle and universal regulatory parameter may provide the initial codes, hints and hunches, of a new synthetic and unitive biological, biomedical and biophysical scientific paradigm. Initially, it already offers the possibility of a new multidisciplinary approach to the prevention and treatment of tumors such as cervical intraepitelial neoplasia. PMID- 7981367 TI - [Quality of life]. PMID- 7981368 TI - [Multiple pulmonary nodules as the initial manifestation of medullary carcinoma of the thyroid]. PMID- 7981369 TI - [Immunologically mediated thrombocytopenia in Legionella pneumophila pneumonia]. PMID- 7981370 TI - [Intestinal tetany as a presentation form of secondary hypoparathyroidism]. PMID- 7981371 TI - [Klinefelter's syndrome and osteoporosis]. PMID- 7981373 TI - [Pleuropericarditis caused by Q fever]. PMID- 7981372 TI - [Testicular seminoma in a patient infected with the human immunodeficiency virus]. PMID- 7981374 TI - [Importance of prevention in primary care odontostomatology]. PMID- 7981375 TI - [Invitation to reflect on congresses. The Organizing Committee of the XIII Congress SemFYC at La Coruna]. PMID- 7981376 TI - [Perception of the success of primary care health promotion in the province of Toledo]. AB - OBJECTIVE: Identification of factors which can condition the perception by Primary Care professionals of success in health promotion. DESIGN: An observation study of a crossover type. PARTICIPANTS: 106 professionals (doctors, nurses and social workers) from 22 health centres in the province of Toledo, who filled in a questionnaire. MEASUREMENTS AND MAIN RESULTS: A non-conditional, multiple, logistic regression analysis was used. The professional satisfied with his/her work, not a doctor and who worked in a health centre open for less than 3 years, presented, against their opposite values, greater probability (OR 3.01, 2.41 and 1.24 respectively) of having a perception of success in health promotion. CONCLUSIONS: Health promotion undertaken in newly-opened centres, which involves in particular non-medical staff and, above all, is carried out by professionals satisfied with their habitual work, has a 77% probability of being considered successful by these professionals. These factors greatly facilitate its propagation in Primary Care. PMID- 7981377 TI - [Study of prescriptions referred back to a health center]. AB - OBJECTIVE: To study referred-back prescriptions, in the areas of source, consumption, cost and information supplied to the family doctor. DESIGN: Descriptive study of a prospective type. SETTING: "La Merced" Health Centre, Cadiz. PATIENTS AND OTHER PARTICIPANTS: All the reports sent over a two-month period from referral specialists (emergency, second level and hospital) to four consulting rooms at the Health Centre. MEASUREMENTS AND MAIN RESULTS: Out of the 6,499 on-demand consultations, 241 attended in order to obtain a referred-back prescription (3.74%). Of the total of 241 reports sent back by specialists, 12%, 7.9% and 69.7% did not report on diagnosis, recommended dosage and length of treatment, respectively. 44.8% were short-term treatments. In 47.7% of the referred-back prescription notes, only one prescription was required. Referred back prescriptions supposed 9% of the prescriptions issued during the period under observation. CONCLUSIONS: The study only measured incidence, therefore underestimating referred-back prescriptions. In 48% of prescriptions, administrative time could have been saved by dispatching the prescription at its place of origin. There was a notable lack of information supplied in the reports, which we interpret as an indirect indicator of poor coordination between different levels of care. When prescription studies are carried out in Primary Care, the prescription profile of the referral specialists must be taken into consideration. PMID- 7981378 TI - [Validity of diagnostic methods in detection of congenital hip luxation in primary care]. AB - OBJECTIVE: To find the validity of the clinical and radiological methods used within Primary Care in the early diagnosis of Congenital Hip Luxation (CHL). DESIGN: A prospective observation study. SETTING: Zaidin-Sur Basic Health Area (HA), Granada. An urban Health Centre. PATIENTS: All new-born and nursing babies born in our HA between October 1991 and March 1993 (N = 352), followed and studied over an average period of 22.4 months (SD = 5.6) (Range, 12 to 30 months). RESULTS: The prevalence of clinically and/or radiologically-based suspected CHL was 19% (Cl 95%; 12.7-25.3%) and the prevalence of confirmed CHL was 4.2% (Cl 95%; 1.96-6.44%). Ortolani-Barlow sensitivity (O-B) was 46.7%, specificity 85.2%; positive predictive value 12.3%, negative predictive value 97.6%, false positives 14.8% and false negatives 53.3%. When positive O-B and/or other positive clinical signs were taken into consideration, sensitivity rose to 73.3% and false negatives went down to 26.7%. If we had not performed radiologies systematically on all the nursing children, we would have missed CHL diagnosis in 1.14% of our basic HA's population-group. CONCLUSION: We question the clinical diagnosis of CHL due to its low sensitivity and an excessive number of false negatives. We recommended systematic testing by means of a diagnostic image method, which could be X-Rays at 3 to 5 months. PMID- 7981379 TI - [Coordination of sectors: the suitability of principles]. AB - OBJECTIVE: To identify the defining characteristics of Primary (PC) and Specialist Care (SC), along with the level of concordance between managers in both sectors in the definition of these characteristics. SETTING: Intermediate course in Administration of the Andalucian School of Public Health, Granada. DESIGN: By means of the Philips 66 technique, followed by consensus construction, the enumeration of the characteristics of care sectors was requested of the managers, who had been previously selected for an Administration course. The procedure was repeated on five different occasions between 1991 and 1993. For each technique four groups were created (two formed by PC and two by SC professionals), in order to obtain self-referred (PC professionals assess PC and the SC ones, SC) and crossed assessments (PC professionals assess SC and vice versa). PARTICIPANTS: 116 professionals in all took part, 55 from the PC sphere, 45 SC and 16 in provincial and/or central services. RESULTS: There was dissonance in the expectations that managers placed in each sector of the health care system. PC managers' views of SC and SC managers' of PC did not coincide with the views of each group of managers on their own health care sector. CONCLUSIONS: When designing activities to coordinate between sectors, a period of clarification, both on the characteristics of each sector and on the expectations placed on each one, should be included. The subsequent negotiation of these can assist the development and maintenance of joint activities to improve coordination. PMID- 7981380 TI - [Adverse reactions to drugs in a health center]. AB - OBJECTIVE: To study the adverse side-effects to medication and define their principle characteristics. DESIGN: A descriptive, crossover, observation study with no random distribution. SETTING: The population cared for at a Health Centre in Toledo. PATIENTS: Those over 15 years old during a 6-month period. MEASUREMENTS AND MAIN RESULTS: 64 adverse side-effects were detected, classified as follows: definite, 10.9%; probable, 68.7%; possible, 20.3%. The rate of adverse side-effects was 2.67 per thousand prescriptions and 2.22 per thousand consultations. Distribution by gender was 62.5% women and 37.5% men. The 35-45 age group was the one with most adverse side-effects. The most affected systems were the digestive apparatus (46.50%), followed by the nervous system (27.50%) and the skin (16.22%). The most commonly involved pharmacological groups were: analgesics and non-steroid anti-inflammatories (34.37%) and drugs for the cardiovascular system (26.56%). 98.43% were trivial and none serious. Evolution was: 59.37% recovered on stopping the drug and 23.43% with the help of treatment. CONCLUSIONS: The number of suspected adverse side-effects in the Centre is high, but they were trivial. It was confirmed that adverse side-effects suppose a frequent medical problem in Primary Care. It is important to make health professionals aware so that, when prescribing, they bear in mind the drug risk/benefit relationship. The identification and communication of adverse side effects, especially of medicines newly on the market, is also important. PMID- 7981381 TI - [Lymphedema in primary care: review of 6 cases]. AB - OBJECTIVE: To study primary care lymphedemas. To outline the differential diagnosis and treatment of late idiopathic lymphedemas. DESIGN: Six clinical observations (descriptive). SETTING: Casa del Barco Health Centre. Valladolid. PATIENTS: Six patients who attended for treatment with oedemas in their extremities. MEASUREMENTS AND MAIN RESULTS: Anamnesis and physical investigation provided the provisional diagnosis. Analytic, echographic and radiological tests, along with internal consultation with Vascular Surgery, oriented the diagnostic impression towards idiopathic lymphedemas; and the histology tests oriented towards secondary ones. A lymphogammagraphy was not performed to confirm the diagnosis, as the diagnosis had already been reached by process of exclusion in the first tests. CONCLUSIONS: Lymphoedema is one of the causes of oedema in the extremities. Anamnesis and physical investigation is fundamental to the clinical diagnosis of lymphatic failure. Other complementary tests (analytic, radiological and histological studies, etc.) are necessary in order to reach an aetiological diagnosis and thus a correct treatment. The definitive diagnosis in idiopathic lymphedemas is provided by a lymphogammagraphy, although this is rarely indicated; and in secondary ones by the tests aimed at showing the cause. Conservative therapeutic measures (hygienic, compressive, physiotherapeutic and pharmacological) avoid advance in Late Idiopathic Lymphoedema, with surgical treatment only being needed in a low percentage of cases. The treatment for Secondary Lymphoedema will be the treatment of its cause. PMID- 7981382 TI - [Non-systematic vaccines. II]. PMID- 7981383 TI - [Importance of qualitative information in family medicine]. PMID- 7981384 TI - [Auto-management in primary care]. PMID- 7981385 TI - [Family medicine and hospital practice in Spain]. PMID- 7981386 TI - [The risk of "balintizing"]. PMID- 7981387 TI - Analysing incomplete longitudinal binary responses: a likelihood-based approach. AB - In this paper, we describe a likelihood-based method for analysing balanced but incomplete longitudinal binary responses that are assumed to be missing at random. Following the approach outlined in Zhao and Prentice (1990, Biometrika 77, 642-648), we focus on "marginal models" in which the marginal expectation of the response variable is related to a set of covariates. The association between binary responses is modelled in terms of conditional log odds-ratios. We describe a set of scoring equations for jointly estimating both the marginal parameters and the conditional association parameters. An outline of the EM algorithm used to obtain the maximum likelihood estimates is presented. This approach yields valid and efficient estimates when the responses are missing at random, but not necessarily missing completely at random. An example, using data from the Muscatine Coronary Risk Factor Study, is presented to illustrate this methodology. PMID- 7981388 TI - Test of homogeneity of binary data with explanatory variables. AB - Apparent heterogeneity of the risk of a disease in different groups may be explained by subject-specific risk factors unequally distributed in these groups. We propose a score test of homogeneity that allows adjustment for known risk factors of the disease. The test is based on a random-effect logistic regression model and requires only simple computations in addition to a conventional logistic regression method. The score test is applied to the study of geographical heterogeneity of cognitive impairment in elderly using a sample of 3,318 subjects scattered in 75 parishes. It is shown that an apparent heterogeneity disappears when taking into account subject-specific risk factors. This test may also be useful for studying familial aggregation of a disease. PMID- 7981389 TI - Parametric approaches to quality-adjusted survival analysis. International Breast Cancer Study Group. AB - We present a parametric methodology for performing quality-of-life-adjusted survival analysis using multivariate censored survival data. It represents a generalization of the nonparametric Q-TWiST method (Quality-adjusted Time without Symptoms and Toxicity). The event times correspond to transitions between states of health that differ in terms of quality of life. Each transition is governed by a competing risks model where the health states are the competing risks. Overall survival is the sum of the amount of time spent in each health state. The first step of the proposed methodology consists of defining a quality function that assigns a "score" to a life having given health state transitions. It is a composite measure of both quantity and quality of life. In general, the quality function assigns a small value to a short life with poor quality and a high value to a long life with good quality. In the second step, parametric survival models are fit to the data. This is done by repeatedly modeling the conditional cause specific hazard functions given the previous transitions. Covariates are incorporated by accelerated failure time regression, and the model parameters are estimated by maximum likelihood. Lastly, the modeling results are used to estimate the expectation of quality functions. Standard errors and confidence intervals are computed using the bootstrap and delta methods. The results are useful for simultaneously evaluating treatments in terms of quantity and quality of life. To demonstrate the proposed methods, we perform an analysis of data from the International Breast Cancer Study Group Trial V, which compared short duration chemotherapy versus long-duration chemotherapy in the treatment of node positive breast cancer. The events studied are: (1) the end of treatment toxicity, (2) disease recurrence, and (3) overall survival. PMID- 7981390 TI - Regression analysis of multivariate grouped survival data. AB - Multivariate failure time data arise when each study subject may experience several types of event or when there are clusterings of observational units such that failure times within the same cluster are correlated. The failure times are often subject to interval grouping or have truly discrete measurements. In this paper, the marginal distribution for each discrete failure time variable is formulated by a grouped-data version of the proportional hazards model while the dependence structure is unspecified. Generalized estimating equations in the spirit of Liang and Zeger (1986, Biometrika 73, 13-22) are proposed to estimate the regression parameters and survival probabilities. The resulting estimators are consistent and asymptotically normal. Robust estimators for the limiting covariance matrices are constructed. Simulation studies demonstrate that the asymptotic approximations are adequate for practical use and that ignoring the intracluster dependence in the variance-covariance estimation would lead to invalid statistical inference. A psychological experiment is provided for illustration. PMID- 7981391 TI - Spline-based tests in survival analysis. AB - This paper examines a method for testing hypotheses on covariate effects in a proportional hazards model, and also on how effects change over time in regression analysis of survival data. The technique used is very general and can be applied to testing many other aspects of parametric and semiparametric models. The basic idea is to formulate a flexible parametric alternative using fixed knot splines, together with a penalty function that penalizes noisy alternatives more than smooth ones, to focus the power of the tests toward smooth alternatives. The test statistics are the analogs of ordinary likelihood-based statistics, only computed from a penalized likelihood formed by subtracting the penalty function from the ordinary log-likelihood. Large-sample approximations to the distributions are found when the number of knots is held fixed as the sample size increases. Numerical results suggest these approximations may be adequate with moderate sized samples. PMID- 7981392 TI - A test of the Markovian model of DNA evolution. AB - The Markov model of molecular evolution has recently received a significant amount of interest because its statistical nature allows for the testing of a number of evolutionary hypotheses. Here we propose a test which assesses whether data from two species sharing a common ancestor will fit a general Markovian model. We illustrate the test with two examples of data which appear at first glance not to fit a Markov model. PMID- 7981393 TI - Robust estimation of gene frequency and association parameters. AB - Methods based on generalized estimating equations are proposed for estimation and testing of gene frequency and association parameters using family data. In the problems considered, a marginal model is used to estimate the gene frequency and association parameters specified in the marginal distributions of the individuals. These procedures are robust in the sense that consistent estimates of the parameters of interest and their standard errors are obtained even though the marginal model is not fully correctly specified. In addition, the methods are shown to have good efficiency when compared with maximum likelihood methods. Specific procedures for application of the methods to the cases of allele frequency estimation, testing of linkage and Hardy-Weinberg disequilibrium parameters, and testing for marker-disease association are outlined and illustrated with data examples. PMID- 7981394 TI - Estimation of incidence of HIV infection using cross-sectional marker surveys. AB - Methods of estimating the probability density function of infection times for a population, using serial cross-sectional measurements of a marker of disease progression, are presented. The infection time distribution may be calculated back to the beginning of the epidemic, if it is possible to sample individuals who were infected at the beginning of the epidemic; otherwise, under a Markov assumption, the infection time distribution may be calculated conditional on infection after sampling has begun. In either case, the proportion of prevalent cases infected in an arbitrary time interval between the onset and termination of sampling may be measured. Data from the San Francisco Men's Health Study are analyzed; the infection time distribution compares well with that estimated by Bacchetti (1990, Journal of the American Statistical Association 85, 1002-1008) using stored sera from several San Francisco cohort studies. PMID- 7981395 TI - Semiparametric models for longitudinal data with application to CD4 cell numbers in HIV seroconverters. AB - The paper describes a semiparametric model for longitudinal data which is illustrated by its application to data on the time evolution of CD4 cell numbers in HIV seroconverters. The essential ingredients of the model are a parametric linear model for covariate adjustment, a nonparametric estimation of a smooth time trend, serial correlation between measurements on an individual subject, and random measurement error. A back-fitting algorithm is used in conjunction with a cross-validation prescription to fit the model. A notable feature in the application is that the onset of HIV infection is associated with a sudden drop in CD4 cells followed by a longer-term slower decay. The model is also used to estimate an individual's curve by combining his data with the population curve. Shrinkage toward the population mean trajectory is controlled in a natural way by the estimated covariance structure of the data. PMID- 7981396 TI - A sample-size-optimal Bayesian procedure for sequential pharmaceutical trials. AB - Consider a pharmaceutical trial where the consequences of different decisions are expressed on a financial scale. The efficacy of the new drug under consideration has a prior distribution obtained from the underlying biological process, animal experiments, clinical experience, and so forth. Berry and Ho (Biometrics 44, 219 227) show how these components are used to establish an optimal (Bayes) sequential testing procedure, assuming a known constant sample size at each decision point. We show in this article how it is also possible to optimize further, with respect to the sample-size rule. This component of the design, which is missing from most sequential procedures, has the potential to yield considerably larger expected net gains (equivalently, considerably smaller Bayes risks). PMID- 7981397 TI - Detectability in conventional and adaptive sampling. AB - In this paper a simple but very general method is given for estimating a population total with any sampling design when objects in sampled units are observed with imperfect detectability--a problem characteristic of many surveys of natural and human populations. In the most general case, the method consists of dividing the value of the variable of interest associated with each detected object by the detection probability for that object and then proceeding to use the estimation method that would ordinarily be used under the design if there were no detectability problems. Examples illustrating the method include simple random sampling, conventional unequal probability sampling, and adaptive cluster sampling. PMID- 7981399 TI - Identification of aperiodic seasonality in non-Gaussian time series. AB - Time series that arise from biological experimentation can exhibit seasonality where the lengths of the seasons may vary. In addition, such time series may not be stationary with respect to either mean, variance, or autocorrelation, thus making the usual waveform-fitting techniques inappropriate. An agglomerative clustering algorithm for identifying seasons in such series is proposed, consisting of an initialization step, iterative steps where clusters are combined into larger clusters, and a stopping rule for the iteration. The clusters can be associated with seasons or phases, and biological cycles can be identified from the phases. Results of a simulation and an analysis of luteinizing hormone concentrations are presented. PMID- 7981398 TI - Statistical analysis of ligand-binding experiments. AB - After a brief review of commonly used methods for parameter estimation from ligand-binding data in the biochemistry literature, we propose some diagnostic checks and statistical tests of the underlying assumptions and develop methods for evaluating the biases and variances of the estimates and for constructing confidence intervals. Examples on the analysis of data from two radioligand binding experiments are presented to illustrate these methods. PMID- 7981400 TI - Combined maximum likelihood estimates for the equicorrelation coefficient. AB - Combined maximum likelihood estimates for equicorrelation covariance matrices are considered. The case of a common equicorrelation rho and possibly different standard deviations sigma 1, ..., sigma k among k experimental groups is examined first, and the estimation of (rho, sigma 1, ..., sigma k) is discussed. Second, under the assumption of a common standard deviation and possibly different equicorrelations, the estimation of (rho 1, ..., rho k, sigma) is considered. In each case, maximum likelihood solutions and corresponding large-sample variances are presented. PMID- 7981401 TI - Regression analysis of grouped survival data with incomplete covariates: nonignorable missing-data and censoring mechanisms. AB - Previous methods for the analysis of survival data with incomplete covariates have assumed that the missing-data and censoring mechanisms are ignorable. We relax both assumptions for the analysis of grouped survival data. PMID- 7981402 TI - Interim analysis for randomized clinical trials: simulating the predictive distribution of the log-rank test statistic. AB - This paper presents an analog to stochastic curtailment, where the simulation of the remaining trial data from interim analysis is constructed using the existing data, rather than the design planning parameters. The nonparametric approach for the predictive distribution as proposed by Berliner and Hill (1988, Journal of the American Statistical Association 83, 772-779) forms the basis of the procedure. The methods are applied retrospectively to a clinical trial in childhood cancer. PMID- 7981403 TI - Simple designs and model-free tests for synergy. AB - Current statistical designs for studying whether two or more agents in combination act synergistically nearly always require the study of several doses of many dose ratios. The analysis is usually based on an assumed parametric model of the dose-response surface. In this paper, for both quantal and quantitative response variables, sufficient conditions are given for establishing synergy at a dose of the combination without the need to specify the model. This enables the use of simple designs with few doses even when there is sparse knowledge of the dose-response curves of the individual agents. The Min test, used for testing whether an identified treatment is best, may be used for testing synergy. Power issues are discussed. PMID- 7981404 TI - Jackknife estimators of variance for parameter estimates from estimating equations with applications to clustered survival data. AB - An estimate of a parameter vector beta is often obtained by setting a "score" vector equal to zero and solving for beta. Estimating equations of this type include maximum likelihood, quasi-likelihood (McCullagh, 1983, Annals of Statistics 11, 59-67), and generalized estimating equations (Liang and Zeger, 1986, Biometrika 73, 13-22). White (1982, Econometrica 50, 1-26) proposed a variance estimator for beta that is robust to model misspecification. We show that a "one-step" jackknife estimator of variance is asymptotically equivalent to the variance estimator proposed by White. The one-step variance estimator may be preferred when the appropriate computer packages are not available to compute White's estimator directly. This jackknife estimator is very useful in our example with clustered survival data. PMID- 7981405 TI - An extension of Yule's Q to multivariate binary data. AB - In this note we describe a summary measure of pairwise association for multivariate binary data based on the conditional odds ratio. The proposed measure is an extension of Yule's Q to more than two binary random variables. Unlike marginal measures of association, this measure is not constrained by the marginal probabilities of success. For example, when each binary variable has a different probability of success, the upper limit of the pairwise marginal correlation coefficient is constrained to be less than 1. If one prefers a measure of association that is unconstrained, then with only two binary variables, Bishop, Feinberg, and Holland (1975, Discrete Multivariate Analysis: Theory and Practice, Cambridge, Massachusetts: MIT Press) suggest the use of the odds ratio or, equivalently, Yule's Q. Yule's Q transforms the odds ratio between the two binary variables from [0, infinity) to [-1, 1]. We propose an extension of Yule's Q to more than two binary random variables. This measure of pairwise association is based on the conditional odds ratio from a log-linear model. PMID- 7981406 TI - On tests against one-sided hypotheses in some generalized linear models. AB - One-sided hypotheses arise naturally in many situations. When testing against such hypotheses, it is desirable to take the available one-sided information into account, rather than simply applying a two-sided test. What we expect to gain by applying a one-sided test instead of a two-sided test is an increase in the power of the test. We consider various tests of one-sided hypotheses in a class of models that includes generalized linear and Cox regression models. The tests are likelihood ratio, Wald, score, generalized distance, and a Pearson chi-square. It is shown that these test statistics are asymptomatically equivalent in terms of local power; this is a generalization of the well-known corresponding result for two-sided alternatives. Two examples are also discussed. They are on (1) testing for interaction in binomial response models, and (2) comparison of treatments with ordinal categorical responses. PMID- 7981407 TI - Mantel-Haenszel-type tests for testing equivalence or more than equivalence in comparative clinical trials. AB - This paper proposes Mantel-Haenszel-type statistics for testing whether a new treatment is at least as effective as the standard treatment in comparative binomial trials. The null hypotheses considered are of a specified nonzero difference and of a ratio not equal to unity. It is shown that we may also use these tests for testing the equivalence of two treatments. PMID- 7981408 TI - Measurement errors in caries diagnosis: some further latent class models. AB - Latent class models have been proposed for assessing relative errors in discrete measurements arising, for example, in caries diagnosis. Those models, however, that turned out to fit empirical data (N = 3,869 teeth, 5 dentists) to a sufficient degree, needed the inclusion of interaction terms for pairs of raters at the latent levels in order to describe the observed interrelations of the judgments. Now it is shown that instead of giving up the concept of local stochastic independence, increasing the number of classes while possibly restricting their parameters in the end has the same effect: Both the unrestricted three-class model, which can be interpreted to be the generalization of the Carlos-Senning assumptions, and a restricted four-class model, which resembles the latent distance model well known from psychometrics, give good and excellent fit, respectively, to the caries data. For the case of the four-class model, a second solution exists that exhibits exactly the same fit, giving rise to warnings against the possibility of multiple solutions to the likelihood equations. PMID- 7981410 TI - Ethical guidelines to publication of chemical research. American Chemical Society. AB - The guidelines embodied in this document were revised by the editors of the Publication Division of the American Chemical Society in January 1994 and endorsed by the Society Committee on Publications. PMID- 7981409 TI - On the use of the quasi-likelihood method in teratological experiments. AB - This paper concerns the impact of litter effects on the inference of dose response relationships in teratological experiments with binary response. Kupper et al. (1986, Biometrics 42, 85-98) concluded that when intra-litter correlations are dose-dependent, the use of a common intra-litter correlation likelihood based on the beta-binomial distribution could lead to severe bias in estimation of the parameter beta, which characterizes the dose-response relationship. We show here that the problems of bias and coverage probability for beta could still be substantial when one uses the likelihood with heterogeneous intra-litter correlations. We then examine through a simulation study the performance of the quasi-likelihood method (Wedderburn, 1974, Biometrika 61, 439-447) and recommend that this method with a common intra-litter correlation parameter be used when the number of litters is small or modest. PMID- 7981411 TI - Transplacental lung carcinogenesis: a pharmacogenetic mouse model for the modulatory role of cytochrome P450 1A1 on lung cancer initiation. PMID- 7981412 TI - Oxidation and radical intermediates associated with the glutathione conjugation of mucochloric acid. AB - The inactivation of the drinking water mutagen mucochloric acid (MCA) by reduced glutathione (GSH) was linked to the formation of an MCA-GSH conjugate, a nonmutagen in the Salmonella typhimurium (TA100) plate incorporation assay. Anaerobic formation of MCA-GSH is found now to be associated with oxidized glutathione (GSSG) and unconverted MCA. The anaerobic reaction of GSH with MCA in the presence of the radical trap 2-methyl-2-nitrosopropane (tNB; "tert nitrosobutane") gives rise to an electron paramagnetic resonance (EPR) resulting from the overlapping spectra of two radical adducts. The first species exhibited hyperfine coupling constants of aN = 13.65 G and aH beta = 0.73 G. The second radical adduct exhibited a three-line signal of aN = 12.8 G. The first species is assigned to an adduct of the MCA radical because deuteration of MCA (5-deuterio MCA) caused the beta-hydrogen hyperfine coupling to collapse. The second radical adduct is unaffected by the deuteration of MCA. Thus, the involvement of both GSSG and a carbon-centered MCA radical in the action of MCA on GSH is indicated. PMID- 7981413 TI - Adducts of dienochlor miticide with glutathione, glutathione S-transferases, and hemoglobins. AB - Dienochlor (Pentac) (C10Cl10) has been used for 30 years as a miticide with little knowledge of its mode of action or metabolic fate except that it is quickly degraded by rats. This study examines the reactions of dienochlor with GSH and proteins as models for its metabolism and interactions with tissues. Dienochlor reacts rapidly with 1.0 mM GSH in phosphate buffer (pH 7.4) at 37 degrees C (t1/2 approximately 11 min) as analyzed by UV/visible spectroscopy and HPLC, yielding a series of more than a dozen adducts. Octachlorofulvalene (C10Cl8), a candidate intermediate, also reacts to give the same apparent products (t1/2 < 0.2 min as above); however, its intermediacy in the dienochlor reaction was not established. Isolation and MS analyses characterized two isomeric C10H2Cl(SG)5 adducts and a C10H2(SG)6 derivative; these products react further in the presence of GSH to yield two even more polar adducts. Cysteine and N-acetylcysteine also react rapidly with dienochlor whereas GSSG and several non thiol amino acids are much less reactive. Purified GSH S-transferases (GSTs) and hemoglobins, each from six species of mammals including humans, are extensively labeled in vitro by [14C]dienochlor to form adducts separable by gel electrophoresis and HPLC. [14C]Dienochlor readily derivatizes rat liver GSTs even in cytosol and in the presence of high GSH levels. The potency of dienochlor for inhibition of GST activity is maintained or enhanced upon conversion to GSH adducts.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7981414 TI - Oxidation and acetylation as determinants of 2-bromocystein-S-ylhydroquinone mediated nephrotoxicity. AB - 2-Bromodiglutathion-S-ylhydroquinone is a more potent nephrotoxicant than 2 bromomonoglutathion-S-ylhydroquinones. In the present study we examined the activity of enzymes involved in mercapturic acid biosynthesis toward both the glutathione conjugates and their cysteine and N-acetylcysteine metabolites and compared the results to the relative nephrotoxicity of these conjugates. Although differences were observed in the kinetics of the gamma-glutamyl transpeptidase (gamma-GT)-mediated hydrolysis and transpeptidation of the glutathione conjugates, the concentration of this enzyme within the kidney probably precludes it from contributing to their differential toxicity. In contrast, the rate at which the cysteine and corresponding mercapturate conjugates underwent N deacetylation/N-acetylation cycling correlated with previously reported differences in toxicity. The relative rates of these two reactions are important because electrochemical data suggest that 2-bromodicystein-S-ylhydroquinone is more readily oxidized to the reactive quinone than its corresponding mercapturic acid. In addition, 2-bromodi(N-acetylcystein-S-yl)hydroquinone, which is the most potent of the mercapturic acid conjugates, exhibited the highest N deacetylation/N-acetylation ratio. In contrast, 2-bromo-3-(N-acetylcystein-S yl)hydroquinone, which is essentially not toxic in vivo, was not a substrate for the renal cysteine conjugate N-deacetylase. The data suggest that the rate determining step for the in vivo toxicity of these conjugates is probably the N acetylation reaction and the availability of the corresponding acetyl-CoA cofactor. PMID- 7981415 TI - An HPLC-EC assay for 1,N2-propano adducts of 2'-deoxyguanosine with 4 hydroxynonenal and other alpha,beta-unsaturated aldehydes. AB - An assay was developed for the 1,N2-propanoguanine adducts generated in DNA by reaction with biologically relevant alpha,beta-unsaturated aldehydes. The analysis takes advantage of the electrochemical activity of the adducts released as modified bases by quantitative acidic hydrolysis of the DNA. The detection limit of the method is around 1 pmol in DNA. Emphasis was placed on the detection of the derivatives of 4-hydroxynonenal (a final product of lipid peroxidation) and hexenal. The adducts were detected in calf thymus DNA incubated with these two unsaturated aldehydes. The 4-hydroxynonenal-1,N2-propanoguanine derivatives were not observed in DNA extracted from young rat kidneys or liver. The technique was shown to be also applicable to a series of alpha,beta-unsaturated aldehydes 1,N2-propanoguanine adducts which were found to be electrochemically active at relatively low potential and efficiently separated by reverse-phase HPLC. PMID- 7981416 TI - Reaction kinetics for nitrosation of cysteine and glutathione in aerobic nitric oxide solutions at neutral pH. Insights into the fate and physiological effects of intermediates generated in the NO/O2 reaction. AB - The critical regulatory function of nitric oxide (NO) in many physiologic processes is well established. However, in an aerobic aqueous environment NO is known to generate one or more reactive and potentially toxic nitrogen oxide (NOx) metabolites. This has led to the speculation that mechanisms must exist in vivo by which these reactive intermediates are detoxified, although the nature of these mechanisms has yet to be elucidated. This report demonstrates that among the primary bioorganic products of the reaction of cellular constituents with the intermediates of the NO/O2 reaction are S-nitrosothiol (S-NO) adducts. Anaerobic solutions of NO are not capable of nitrosating cysteine or glutathione, while S NO adducts of these amino acids are readily formed in the presence of O2 and NO. Investigation of the kinetics for the formation of these S-NO adducts has revealed a rate equation of d[RSNO]/dt = kSNO[NO]2[O2], where kSNO = (6 +/- 2) x 10(6) M-2S-1, a value identical to that for the formation of reactive intermediates in the autoxidation of NO. Competition studies performed with a variety of amino acids, glutathione, and azide have shown that cysteine residues have an affinity for the NOx species that is 3 orders of magnitude greater than that of the nonsulfhydryl amino acids, and > 10(6) times greater than that of the exocyclic amino groups of DNA bases. The dipeptide alanyltyrosine reacts with the intermediates of the NO/O2 reaction with an affinity 150 times less than that of the sulfhydryl-containing compounds. Furthermore, Chinese hamster V79 lung fibroblasts depleted of glutathione display enhanced cytotoxicity on exposure to NO.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7981418 TI - An ab initio computational molecular orbital study of the conformers of muconaldehyde, and the possible role of 2-formyl-2H-pyran in bringing about the conversion of a (Z,Z)-muconaldehyde structure into an (E,Z)-muconaldehyde structure. AB - To determine whether conformers of 2-formyl-2H-pyran (2F2HP) can serve as intermediates in the isomerization (Z,Z)-muconaldehyde-->(E,Z)-muconaldehyde--an essential step in the metabolic oxidation of benzene in which (E,E)-muconic acid is formed--we have carried out ab initio molecular orbital calculations at the MP2/6-31G* (frozen core, valence orbitals active) level with full geometry optimization at the RHF/6-31G* level. Taking account of the configuration about the carbon-carbon single bonds as well as that about the double bonds, the six conformers of (Z,Z)-muconaldehyde have been characterized, as well as the eight conformers of (E,Z)-muconaldehyde. Axial and equatorial conformers of 2F2HP have been identified, which exist in stable syn or anti forms depending on the relative position of the pyran and carbonyl O-atoms. Each step in the metabolic pathway is stereospecific. The initial ring opening in 2,3-epoxyoxepin gives (eZzZz)-muconaldehyde, which then undergoes ring closure to give anti-axial-2F2HP (step a). Inversion of the ring gives anti-equatorial-2F2HP, which upon ring opening gives (zEzZz)-muconaldehyde (step b). An alternative pathway links (zZzZz)-muconaldehyde with syn-axial-2F2HP (step a'), and syn-equatorial with (eEzZz)-muconaldehyde (step b'). Half-reaction times, taking into account the fractional representation of each reacting conformer in rapidly established equilibrium mixtures, suggest that the operative pathway is via step a, with little to choose between steps b and b'. PMID- 7981417 TI - Identification of novel glutathione conjugates of disulfiram and diethyldithiocarbamate in rat bile by liquid chromatography-tandem mass spectrometry. Evidence for metabolic activation of disulfiram in vivo. AB - Recent studies have shown that the inhibitory effects of disulfiram and diethyldithiocarbamate (DDTC) (to which disulfiram is rapidly reduced in vivo) on the liver mitochondrial low-Km form of aldehyde dehydrogenase (ALDH) may be mediated by a reactive metabolite(s) of these compounds. In order to investigate the nature of such electrophilic intermediates in vivo, the present study was carried out with the goal of detecting and identifying their respective glutathione (GSH) conjugates in the bile of rats dosed ip with either disulfiram (75 mg kg-1) or sodium DDTC (114 mg kg-1). By means of highly selective screening strategies based on coupled liquid chromatography-tandem mass spectrometry techniques, one major and four minor GSH adducts were identified as common biliary metabolites of disulfiram and DDTC. The major conjugate, whose excretion into bile over 4 h accounted for ca. 1% of the dose of either precursor, was identified as S-(N,N-diethylcarbamoyl)glutathione (SDEG). In vitro experiments with synthetic SDEG demonstrated that this carbamate thioester derivative is chemically stable in aqueous media under physiological conditions and does not carbamoylate nucleophiles such as cysteine. Consistent with these findings, SDEG failed to inhibit yeast ALDH in vitro. The minor GSH conjugates in bile were identified as S-(N,N-diethylthiocarbamoyl)glutathione, S-(N-ethyl carbamoyl)glutathione, S-(N-ethylthiocarbamoyl)glutathione, and S-[N (carboxymethyl)-N- ethylcarbamoyl]glutathione, the structures of which indicate that metabolic oxidation takes place at the thiono sulfur group and at each of the carbon atoms of disulfiram and DDTC.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7981419 TI - Effect of ligand structure on formation and DNA binding properties of the transformed rat cytosolic aryl hydrocarbon receptor. AB - The saturation binding of transformed rat hepatic aryl hydrocarbon (Ah) receptor with [32P]-dioxin responsive element was determined using gel mobility shift assays. The assay was carried out with ligands which exhibit both high and low Ah receptor agonist activity, namely: (high) 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), 2,3,7,8-tetrachlorodibenzofuran (TCDF), 1,2,3,7,8-pentachlorodibenzo-p dioxin, and 1,2,3,7,8-pentachlorodibenzofuran; and (low) 1,2,7,8-TCDF, 2,3,7 trichlorodibenzo-p-dioxin and 6-methyl-1,3,8-trichlorodibenzofuran (MCDF). Woolfplot analysis of the saturation binding data revealed that for the concentrations of ligands used in this study the Bmax values for the high affinity ligands were significantly higher (36.9-39.4 fmol/mg) than observed for the low-affinity ligands (6.15-13.8 fmol/mg). In contrast, there was not a structure-dependent trend in the equilibrium constant for dissociation KD values or in the half-lives (t1/2) for decomposition of the transformed receptor complexes. MCDF, a partial Ah receptor agonist/antagonist, also transformed the cytosolic Ah receptor and inhibited TCDD-induced transformation as determined by gel mobility shift assays. However, the diagnostic value of this assay to detect partial Ah receptor antagonists is questionable since similar results were obtained with 1,2,7,8-TCDF, a ligand which does not exhibit partial antagonist activity. PMID- 7981420 TI - Formation and structure of cross-linking and monomeric pyrrole autoxidation products in 2,5-hexanedione-treated amino acids, peptides, and protein. AB - 2,5-Hexanedione (2,5-HD) is the neurotoxic gamma-diketone metabolite of the industrial solvent n-hexane. Substantial evidence indicates that 2,5-HD reacts with neurofilament protein lysine epsilon-amines to yield 2,5-dimethylpyrrole adducts and that this reaction is critical to the mechanism of toxicity. Alkylpyrroles are susceptible to autoxidative dimerization, a process that has also been suggested as an obligatory step in 2,5-HD neuropathy. In the present study, we characterized pyrrole autoxidation products of a 2,5-HD-treated lysine analogue and of a model, lysine-containing dipeptide and examined mechanistic aspects of pyrrole-mediated protein cross-linking. Incubation of 2,5-HD with N alpha-acetyllysine or the dipeptide N alpha-acetylglycyllysine methyl ester in physiological buffer (pH 7.4) under oxidative conditions resulted in time dependent formation of the N epsilon-pyrrole derivative and two major pyrrole autoxidation products, as demonstrated by HPLC, on-line thermospray MS, and UV photodiode array detection. An autoxidative pyrrole dimer containing a methylene bridge between C-2 of one pyrrole ring and C-3 of a second ring was characterized by thermospray MS and 1H-NMR spectroscopy. 13C-NMR spectroscopy provided evidence for an identical pyrrole-to-pyrrole bridge in autoxidized, pyrrolylated ribonuclease (RNase). MS analysis also revealed a second major product--a stable, oxygen-containing monomeric pyrrole derivative. This product exhibited a UV absorbance maximum (lambda max = 355 nm) consistent with extended conjugation. Polymerization of pyrrolylated acetyllysine was accelerated by persulfate, a free radical initiator, and inhibited by ascorbate, an antioxidant.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7981421 TI - Mutagenicity and cytotoxicity of naphthoquinones for Ames Salmonella tester strains. AB - The molecular mechanisms involved in quinone cytotoxicity, especially mutagenicity, are still largely unknown. In order to better understand the molecular aspects of the mechanisms of quinone mutagenicity and cytotoxicity, we examined them by using a series of 13 simple structural naphthoquinone (NQ) derivatives for 9 Ames Salmonella mutagenicity tester strains in the presence of absence of liver homogenate S9 mix from rats induced with phenobarbital and 5,6 benzoflavone. Most NQs used in this study showed mutagenicity with and/or without S9 mix. The most potent mutagenic NQ was 2,3-dichloro-1,4-NQ, with mutagenicity of 18 induced revertants/nmol/plate for strain TA104 without S9 mix. Among the strains used, TA104, which is sensitive to oxidative mutagens, was the most sensitive to the NQs, and the second most sensitive strain was TA2637, which detects bulky DNA adducts. The relationship of mutagenic potency to the one electron reduction potential with TA104 suggested that the higher redox potential NQs were more mutagenic than the lower redox potential NQs. Significant reduction of the mutagenicity of 1,4-naphthoquinone without S9 mix was observed in the presence of catalase. Enhancement of the mutagenic potential of the NQs by the pKM101 plasmid implicated in error-prone repair was also observed. The most cytotoxic NQ was 2,3-dichloro-5,8-dihydroxy-1,4-NQ, and the least cytotoxic NQ was beta-NQ-4-sulfonic acid potassium salt, a 700-fold range in potency. The cytotoxic effect of the NQs was largely dependent on the structures of their substituents.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7981422 TI - Kinetics of the reaction of nitric oxide with oxygen in aqueous solutions. AB - An understanding of the rate of reaction of nitric oxide (NO) with oxygen in aqueous solutions is needed in assessing the various actions of NO in the body. A novel approach was developed for studying the kinetics of this reaction, which permitted simultaneous and continuous measurements of the concentrations of NO and the principal product, nitrite (NO2-). Nitric oxide was measured using a chemiluminescence detector, with continuous sampling achieved by diffusion of NO through a membrane fitted into the base of a small, stirred reactor. The results with various initial NO and O2 concentrations confirmed that the rate of reaction is second-order in NO and first-order in O2. The rate of reaction of NO was described by the expression 4k1 [NO]2[O2], where k1 was (2.1 +/- 0.4) x 10(6) M-2 s-1 at 23 degrees C and (2.4 +/- 0.3) x 10(6) M-2 s-1 at 37 degrees C. The value of k1 was the same at pH 4.9 and 7.4. The rate of formation of NO2- equaled the rate of reaction of NO (within experimental uncertainty of a few percent), and there was no detectable formation of nitrate (NO3-). This confirmed that NO and NO2- were the only NOx species present in significant amounts and supported the validity of pseudo-steady-state assumptions for NO2 and N2O3, which are intermediates in the conversion of NO to NO2-.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7981423 TI - Metabolic activation and immunochemical localization of liver protein adducts of the nonsteroidal anti-inflammatory drug diclofenac. AB - Diclofenac is a nonsteroidal anti-inflammatory agent that is reported to cause serious hepatic injury in some patients. To investigate the possibility that protein adducts derived from reactive intermediates of diclofenac might be responsible for the hepatotoxicity produced by this drug, we recently developed polyclonal antisera that recognized protein adducts of diclofenac. In the present study, we have characterized further the diclofenac adducts in rat liver. Immunoblotting studies showed that diclofenac-labeled hepatic proteins were formed in a dose- and time-dependent manner in rats given diclofenac. Subcellular fractionation of liver homogenates from diclofenac-treated rats showed that a 50 kDa microsomal protein and 110-, 140-, and 200-kDa plasma membrane proteins were labeled preferentially. Immunofluorescence studies of isolated hepatocytes and immunohistochemical analysis of liver slices from diclofenac-treated mice and rats confirmed that plasma membrane proteins were labeled by diclofenac metabolites and showed that the bile canalicular domain of the plasma membrane was a major site of diclofenac adduct formation. Additionally, we found that cytochrome P-450 and UDP-glucuronosyltransferase, but not acyl-CoA synthase, catalyzed the formation of reactive intermediates of diclofenac that were bound covalently to proteins in vitro. The metabolites catalyzed by cytochrome P-450 in vitro were bound exclusively to a 50-kDa microsomal protein, even in the presence of albumin. In contrast, the 110-, 140-, and 200-kDa plasma membrane proteins as well as others appeared to be labeled when diclofenac was activated by UDP glucuronosyltransferase.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7981424 TI - Pharmacokinetics of a novel retinoid AGN 190168 and its metabolite AGN 190299 after intravenous administration of AGN 190168 to rats. AB - The pharmacokinetics of AGN 190168, a novel synthetic retinoid, and its major metabolite, AGN 190299, in rat blood after intravenous administration was investigated. Approximately 4.4 mg kg-1 (high dose) or 0.49 mg kg-1 (low dose) of AGN 190168 was administered to rats via the femoral vein. Blood was collected from the femoral artery at various time points during an 8 h period. Blood concentrations of AGN 190168 and AGN 190299 were determined by a specific and sensitive high-pressure liquid chromatographic (HPLC) method. AGN 190168 was rapidly metabolized in rats. The only detectable drug-related species in the blood was AGN 190299. Therefore, only pharmacokinetics of AGN 190299 were calculated. Elimination of AGN 190299 appeared to be non-linear after administration of the high dose, and linear after administration of the low dose. The maximum elimination rate (Vmax) and the concentration at half of the Vmax (km), as estimated by a Michaelis-Menten one-compartment model, were 7.58 +/- 2.42 micrograms min-1 (mean +/- SD) and 6.10 +/- 1.58 micrograms mL-1, respectively. The value of the area under the blood concentration time curve (AUC) was 9.54 +/- 1.68 micrograms h mL-1 after administration of the high dose and 0.594 +/- 0.095 micrograms h mL-1 after administration of the low dose. The clearance value was 7.79 +/- 1.20 mL min-1 kg-1 after the high dose, statistically significantly different from that after the low dose (p < 0.05), 14.0 +/- 2.2 mL min-1 kg-1. The terminal half-life (t1/2) was 1.25 +/- 0.74 h for the high-dose group and 0.95 +/- 0.16 h for the low-dose group. Study results demonstrate rapid systemic metabolism of AGN 190168 to AGN 190299, non-linear pharmacokinetics of AGN 190299 after the 4.4 mg kg-1 dose, and the lack of difference in disposition profiles between sexes after intravenous administration of AGN 190168 to rats. PMID- 7981425 TI - Intestinal absorption pathway of gamma-aminobutyric acid in rat small intestine. AB - Intestinal absorption of gamma-aminobutyric acid (GABA), as a model compound for gamma-aminoacids, has not been extensively studied from the kinetic viewpoint. Since data from our laboratory suggested that some competition arises between intestinal absorption of beta-alanine and GABA and since our intent was to maintain the aqueous stagnant diffusion layer in order to approach absorption tests to in vivo physiological conditions, a rat jejunum in situ study was undertaken in order to gain an insight into the mechanism of GABA absorption. In the present paper, results from assays using isotonic perfusion solutions with starting GABA concentrations ranging from 1 to 50 mM are reported. They show that the intestinal absorption of the gamma-aminoacid can be apparently described as a specialized transport mechanism which obeys Michaelis-Menten and first-order kinetics. Parameter values found were Vm = 13.99 +/- 2.37 mM h-1, Km = 3.87 +/- 0.63 mM, and ka(passive) = 0.362 +/- 0.120 h-1. Through the perfusion of 5 mM beta-alanine solutions containing variable concentrations of GABA (from 5 to 50 mM), a partially competitive inhibition of beta-alanine absorption was apparently characterized. PMID- 7981426 TI - Influence of gamma-aminobutyric acid on baclofen intestinal absorption. AB - Since previous studies suggested that baclofen absorption in the rat middle intestine was inhibited by beta-alanine and therefore mediated, at least in part, by the beta-aminoacid carrier, we focused our new studies on the analysis of the possible inhibition of the drug by a gamma-aminoacid model compound, gamma aminobutyric acid (GABA). A rat jejunum in situ study was undertaken in order to evaluate the effect of GABA on baclofen absorption and to establish the inhibition model. Assays using isotonic perfusion solutions of 0.5 mM baclofen with starting GABA concentrations ranging from 0 to 100 mM are reported. The results show that the absorption rate pseudoconstants of the drug decrease at the GABA concentration increases, with a limiting value of 0.65 h-1 (+/- 0.01). A partial competitive inhibition or complete competitive inhibition in the presence of a passive component could define the interaction phenomena between the two substances. Kinetic absorption parameters for GABA in the presence and absence of baclofen (Ki = 5.67 +/- 1.54, Km = 3.87 +/- 0.63) suggest the existence of more than one intestinal carrier system for baclofen or GABA. PMID- 7981427 TI - A comparison of HPLC and bioassay methods for plasma melanotan-II (MT-II) determination: application to a pharmacokinetic study in rats. AB - The pharmacokinetic profile of the melanotropic peptide, melanotan-II (MT-II), was determined in rats following a 0.3 mg kg-1 intravenous dose. Regression analysis of the plasma MT-II concentrations determined using HPLC and bioassay methods indicated the existence of a significant linear correlation (r = 0.90, p < 0.001). The plasma concentration versus time plots determined using the two assay methods yielded biphasic disposition profiles that were essentially superimposable. The following pharmacokinetic parameters were assessed from plasma concentration versus time data using both methods: Cmax, AUC, CLs, t1/2 beta, MRT, Vd beta, and Vss. Statistical comparison showed that the parameters measured by each method were not significantly different (at the 0.05 level) except for t1/2 beta, MRT and Vss. The presence of even one aberrant data point in the beta-phase can significantly influence t1/2 beta when only a few data points are available in the beta-phase. Since MRT and Vss were calculated from t1/2 beta it is not surprising that these two parameters also differed between methods. PMID- 7981428 TI - The pharmacokinetics of methotrexate after intravenous administration of methotrexate-loaded proliposomes to rats. AB - The pharmacokinetics and tissue distribution of methotrexate (MTX) were investigated after intravenous (i.v.) injection of free MTX (treatment I), MTX loaded proliposomes (treatment II), and empty proliposomes mixed manually with free MTX (treatment III), 8 mg kg-1, to rats using an HPLC assay. After i.v. infusion in 1 min, the plasma concentration of MTX (Cp), the area under the plasma concentration-time curve (AUC, 639 versus 913 micrograms min mL-1), the terminal half-life (t1/2, 48.8 versus 397 min), the mean residence time (MRT, 8.40 versus 325 min), and the apparent volume of distribution at steady state (Vss, 98.1 versus 2800 mL kg-1) were significantly higher; however, the total body clearance (CL, 12.5 versus 8.76 mL min-1 kg-1), renal clearance (CLR, 4.49 versus 2.78 mL min-1 kg-1), non-renal clearance (CLNR, 7.50 versus 5.99 mL min-1 kg-1), and the amount of MTX excreted in urine (Xu, 808 versus 685 micrograms, p < 0.0948) were significantly lower from treatment II than from treatment I. This could be due to the fact that some of the MTX-loaded liposomes (formed immediately after hydration of MTX-loaded proliposomes) are entrapped in tissues and the rest are present in the plasma (higher MRT and Vss from treatment II), and MTX is slowly released from MTX-loaded liposomes (higher t1/2 from treatment II). In the present HPLC assay, the concentrations of MTX represent the sum of free MTX and MTX loaded in liposomes (higher Cp and AUC, slower CL from treatment II). After i.v. infusion in 1 min, some pharmacokinetic parameters, such as t1/2, MRT, and Vss, were significantly different between treatments I and III; however, the differences seemed to be smaller than those between treatments I and II. After 30 min from i.v. infusion, the tissue to plasma (T/P) ratios of MTX in kidney and stomach from treatment II were significantly lower than those from treatment I. This suggested that the i.v. administration of MTX-loaded proliposomes might have fewer side effects in the organs than that of free MTX. The mean amount of MTX loaded in MTX-loaded proliposomes was 2.54 mg/g proliposomes and the MTX was released slowly from hydrated MTX-loaded proliposomes when incubated with phosphate-buffered saline (PBS), rat plasma, or rat liver homogenate. PMID- 7981429 TI - The bioavailability and nonlinear pharmacokinetics of MK-679 in humans. AB - MK-679 (R(-)-3-((3-(2-(7-chloro-2-quinolinyl)ethenyl)phenyl)(3- (dimethylamino)-3 oxo-propyl)thio)methyl)thio)propanoic acid) is a potent and specific LTD4 receptor antagonist. The disposition of MK-679 was investigated in a three-way crossover study in 12 healthy males receiving single intravenous doses of 75, 250, and 500 mg of MK-679. A greater than proportional increase in the area under the plasma concentration-time curve of MK-679 was observed with increase in dose. The plasma concentration data for each subject fitted well to the differential equations for a two-compartment model with linear tissue distribution and Michaelis-Menten elimination from the central compartment, indicating that the elimination of MK-679 in humans is saturable. In a previous study, the disposition of MK-679 in humans was also dose-dependent when given together with its S(+)-isomer, L-668,018. Thus, the disposition of MK-679 in humans is dose dependent regardless of the presence of its stereoisomer. Also, the bioavailability of MK-679 was determined in six healthy males receiving simultaneously an oral dose of 250 mg of MK-679 and intravenous infusion of 1 mg 14C-MK-679. Results of this study indicate that the oral bioavailability of MK 679 is nearly quantitative. PMID- 7981430 TI - The effect of oral dose volume on the absorption of a highly and a poorly water soluble drug in the rat. AB - The influence of dose volume on drug absorption following oral administration of a highly and a poorly water soluble drug was examined in male Sprague-Dawley rats. A constant mass of each 14C-labeled compound was given via gavage in dose volumes of 1, 5, 10, and 20 mL kg-1. Blood levels, as well as the quantitative excretion of radioactivity, were measured following each treatment. No significant changes in either the rate or extent of absorption of the water soluble drug were detected. In contrast, the absorption rate of the poorly water soluble drug increased with higher dose volumes, whereas no changes in the extent of absorption were observed. Drug solubility and gastric emptying appeared to be important factors affecting the rate of absorption of the poorly water soluble drug. Since changes in dose volume may affect the absorption characteristics of orally administered compounds, and the extent of such changes may be dependent upon the physicochemical properties of the drug, it is apparent that dose volume is an important experimental variable to be considered in studies comparing absorption data. PMID- 7981431 TI - Effects of benidipine hydrochloride (Coniel), a new calcium antagonist, on the cardiac output, regional blood flow and vascular resistance in conscious, spontaneously hypertensive rats. AB - Benidipine hydrochloride is a calcium antagonist with a 1,4-dihydropyridine derivative structure, and exhibits long-lasting antihypertensive effects by inhibiting the voltage-dependent Ca2+ channels. This study was undertaken to examine the effect of benidipine on central haemodynamics and regional blood flow (RBF) after intravenous administration of benidipine in conscious, spontaneously hypertensive rats. The microsphere method was used to measure cardiac output and RBF before and after the drug administration, using microspheres labelled with 57Co and 51Cr. Thirty minutes after the intravenous administration of benidipine (3 micrograms kg-1), the mean arterial pressure fell by 15% without significantly increasing the heart rate. The cardiac output increased by 41% and the systemic resistance decreased by 39%. Benidipine significantly increased RBF by 37, 35, and 22% in kidney, heart, and small intestine, respectively, and decreased vascular resistance by 38, 38, and 32%, respectively. We concluded that benidipine reduced blood pressure by increasing RBF in the kidney and heart, while keeping RBF in other organs at a normal level. These results will provide a fundamental basis in support of the clinical benefits of benidipine for hypertensive patients, particularly those with renal failure. PMID- 7981432 TI - Numerical simulation of the peristaltic reflex of the small bowel. AB - A mathematical model and results of numerical simulation of the peristaltic reflex development of the small bowel are presented. The organ is modeled as a soft orthotropic cylindrical biological shell, reinforced by the smooth muscle elements. Their mechanical activity is under the control of a simple reflex arc represented by a single cholinergic neurone. The dynamical reaction starts as a response to the depolarization wave propagating along the smooth muscle layers. The muscle layers contract independently but in a coordinated way with the generation of active forces. The mechanical properties of the wall are supposed to be nonlinear. Deformations of the bioshell are finite. The governing system of equations is obtained and solved numerically. The finite-difference method of second-order accuracy over the time and space variables has been used. The dynamics of stress-strain distribution in the biological shell and shape changes are analyzed. It is shown that there is no axial symmetry in the organ's deformation during the first (preliminary) stage of motor reaction. Only with the development of propulsive contractions is the symmetry observed. PMID- 7981433 TI - Rheology of the vitreous body: Part 2. Viscoelasticity of bovine and porcine vitreous. AB - The viscoelastic properties of the vitreous body from bovine and porcine eyes were determined by microrheometry. Each vitreous sample was sectioned into anterior, central and posterior segments. The rheological properties of each species and region were compared with each other and with the viscoelastic properties of human vitreous reported earlier. The results showed significant variations among species, as well as between regions in all species. All regions of human vitreous have significantly different rheological properties from those of the cow, and from the anterior and posterior regions of the pig; however, the viscoelastic behavior of the central porcine region closely resembles that of the human. In comparing the three species, the major differences found are in those parameters characterizing "viscous" or dissipative properties; values of "elastic" or energy storage properties were similar. PMID- 7981434 TI - Rheology of the vitreous body: part 3. Concentration of electrolytes, collagen and hyaluronic acid. AB - The vitreous body from bovine, porcine, and human eyes was analyzed for concentration of selected components. Each vitreous sample was sectioned into anterior, central, and posterior segments. The segments were analyzed for concentration of Ca+2, Cl-, Na+, and K+, as well as of Collagen and Hyaluronic acid. The four electrolytes showed significant differences between species, but no significant regional variations. The two macromolecules showed significant differences with respect to both species and region within the vitreous. Comparison of these results with previously determined rheological values for the three species revealed a number of unexpected results, such as higher polymer concentrations on average being associated with lower values of viscosity parameters. The results are analyzed in terms of possible compositional differences among species and effects of electrolytes on the viscoelastic behavior of the vitreous' macromolecules. PMID- 7981435 TI - Agglutination-induced erythrocyte deformation by two blood group A-specific lectins: studies by light and electron microscopy. AB - The adhesive energy in lectin-induced agglutination can be assessed by the deformation of erythrocytes in aggregates. Helix pomatia (HPA) and Dolichos biflorus (DBA) specifically agglutinated blood group A erythrocytes and induced a change in curvatures of cells at the end of the aggregates. The curvatures changed from concavity to convexity with increasing lectin concentrations. HPA induced aggregates achieved the theoretical maximal end cell curvature of 0.27 microns-1 at 2-3 micrograms/ml; DBA-induced aggregates approached 0.23 microns-1, requiring 400 micrograms/ml. At any given lectin concentration, HPA showed greater surface binding, caused higher cell curvatures, induced larger aggregate size, and had greater adhesive energies, as compared to DBA. HPA and DBA are globular proteins with a diameter of approximately 5.5 nm and approximately 6.1 nm, respectively, as revealed by the negative staining electron microscopy. The former induced uniform intercellular spacing (approximately 15 nm), whereas the latter induced both smooth (approximately 20 nm) and ruffled spacings. The uniform intercellular spacing was not a function of lectin concentrations. Microscopic studies of erythrocyte deformation provided morphological correlates of biophysical findings of differential adhesive energies induced by these two blood group A-specific lectins. PMID- 7981437 TI - Effect of concentration on enhanced sedimentation rate of erythrocytes in an inclined vessel. AB - The enhanced rate of sedimentation of erythrocytes in an inclined rectangular vessel was measured under microscopic and macroscopic conditions. The velocity profile, V(x), and the thickness, delta, of the upflow layer generated below the downward-facing wall in the sedimentation vessel were measured under a microscope with polystyrene latex as a tracer particle. Here, x is the distance from the vessel wall. All the data of the velocity profile are represented by a single curve, [Vmax- V(x)]/Vmax = [(delta -x)/delta]2, irrespective of the volume fraction, H, and tilt angle, theta, in the range of 0.05 < H < 0.30 and 10 degrees < theta < 40 degrees, where Vmax is the maximum velocity found at the upflow boundary. The rate of fall of the top surface of the suspension v(H, theta) fits the function, v(H, theta) = v(0, theta)(1-H)exp[-(aH + bH2)], well, irrespective of H and theta. These experimental results are compared with the theory of Acrivos and Herbolzheimer. PMID- 7981436 TI - Flow visualization analysis of pulsatile flow in elastic straight tubes. AB - Effects of wall compliance on the flow characteristics were studied by visualizing pulsatile flow in two straight elastic tubes having different compliance and in a rigid tube. The elastic tubes were made of segmented polyether polyurethane and their compliance was adjusted by varying the wall thickness. Their diameter changes were +/- 3.3 and +/- 4.9% for the pressure pulsation between 20 and 250 mm Hg. An acrylic pipe was used for the rigid model. An air-driven artificial heart was used to generate the pulsatile flow having the mean Reynolds number and frequency parameter of 740 and 11.4, respectively. The flow was visualized by the hydrogen bubble method at every 5% of the pulsatile flow cycle. Velocity distributions along the tube diameter were determined from still images of time lines taken with a CCD camera. The ratio of the wall shear rate in the elastic tubes to that in the rigid tube at each phase correlated well with the radial velocity of tube wall, while it had no significant correlation with the instantaneous tube diameter. These results suggest that the wall compliance either increases or decreases the wall shear rate depending on the phasic relation between the flow and pressure waves. When studying the hemodynamic effects on vascular diseases by model experiments, it may be important to take wall elasticity into account. PMID- 7981438 TI - Decreased deformability of red cells in refractory anemia and the abnormality of the membrane skeleton. AB - Rheological characteristics of red cells in two patients with refractory anemia (with single chromosomal abnormality of 20q- or 13q-, respectively) were investigated with the hematological and biochemical properties. (1) Whole blood viscosity was remarkably increased, and the red cell deformability was greatly impaired (the impairments were prominent in patient with 20q-). (2) The hematocrit of both patients was about half of the normal value. Remarkable anisocytosis with elliptocytes and poikilocytes was observed in the patient with 20q-, but the anisocytosis was not so prominent in the patient with 13q-. (3) 2,3 diphosphoglycerate content in red cells was markedly increased in both patients, but adenylate content was not. (4) The red cells were slightly resistant to osmotic hemolysis, but they were not heat-labile. (5) Structural abnormality of spectrin was suggested from the impaired dimer-dimer association in red cell membrane and from the different susceptibility of spectrin to tryptic digestion. In conclusion, the rheological impairments and the abnormal shape of red cells in refractory anemia probably originated from the structural abnormality of cytoskeletal proteins in membrane, and the functional and structural abnormality may be different among patients. PMID- 7981440 TI - 3rd International Symposium on Biofluid Mechanics. July 16-19, 1994, Munich, Federal Republic of Germany. Abstracts. PMID- 7981439 TI - On whole blood viscosity measurements in healthy individuals and in rheumatoid arthritis patients. AB - Different methods of measuring whole blood viscosity using a couette rotational viscometer were compared to establish its use in clinical rheumatological practice. The relationship between blood viscosity and hematocrit was approximately exponential and no significant differences in the slopes were found between healthy controls and rheumatoid arthritis patients. Correction of native blood viscosity to a standard hematocrit of 40% by extrapolation from a standard regression curve, established by concentration/dilution of samples from healthy persons to correct for hematocrit differences and at shear rate 92s-1, was the best method for differentiating between viscosities of patients and controls. It was also the least laborious method, requiring the smallest amounts of blood and having the lowest method error. Native blood viscosity, corrected blood viscosity, plasma viscosity and red cell aggregation were all significantly higher and hematocrit significantly lower in rheumatoid arthritis patients than in controls. PMID- 7981441 TI - Immunohistochemical demonstration of metallothionein in normal human breast tissue and benign and malignant breast lesions. AB - Metallothioneins (MTs) are a set of low molecular weight proteins with a high binding affinity to metal ions. MT over-expression has been recently demonstrated in invasive ductal carcinoma of the breast with poor clinical prognosis. In the present study, MTs have been immunohistochemically investigated in normal human breast tissue and a variety of benign, pre-invasive, and malignant breast lesions. In normal breast tissue, MTs were present in myoepithelial cells whereas the vast majority of luminal cells were MT negative. In lesions without increased cancer risk (adenosis and scleradenosis), MT was only immunolocalized in myoepithelial cells. In papillomas, MT was also found exclusively in myoepithelial cells. In most cases of epitheliosis, both the luminal and myoepithelial cells expressed MT. Atypical lobular hyperplasia, lobular carcinoma in situ, and 13/15 invasive lobular carcinomas showed no MT over-expression. The two invasive lobular carcinomas with MT over-expression were classified as pleomorphic lobular carcinomas with apocrine differentiation. In contrast to lobular cancerization, 12/24 ductal in situ carcinomas and 9/20 invasive ductal carcinomas showed MT over-expression. In situ components found within invasive ductal carcinomas usually reflected the MT status of their invasive counterpart. It is concluded from our immunohistochemical results that breast carcinoma cases with MT overexpression arise from lesions which also show MT overexpression. Thus MT expression in carcinomas may be regarded as a genuine feature of the tumour cells and seems not to be related to endogenous or exogenous factors known to induce MT synthesis. PMID- 7981442 TI - The epidemiological profile of women with an interval cancer in the DOM screening programme. AB - Risk factors for breast cancer were compared in 107 women with interval breast cancer (cancers occurring within 2 years after a negative screen) and 258 women with breast cancer detected at 1st screening. All women (aged 40-67) were screened in the DOM project (the Utrecht programme for the early detection of breast cancer). Women with an interval cancer reported more often a history of benign breast disease (OR 4.66, 95% C.I. 2.08-10.41) and an artificial menopause (OR 4.07; 95% C.I. 1.74-9.55) than women with a screen detected cancer. Women with an interval cancer were taller than women with a screen detected cancer; this was seen most clearly in women with an artificial menopause (chi 2 for trend = 5.88; p = 0.02) and to a lesser extent in premenopausal women (chi 2 for trend = 1.70; p = 0.19). Premenopausal women with an interval cancer were heavier than women with a screen detected cancer (chi 2 for trend = 4.66; p = 0.03); whereas natural postmenopausal women with an interval cancer were leaner than women with a screen detected cancer (chi 2 for trend = 1.57; p = 0.21). All analyses were done while correcting for age and selected other risk factors for breast cancer. These results suggest that the epidemiological profile of pre- and post menopausal women with an interval cancer differs from that of women with a screen detected cancer, which might imply a different natural history of these two types of breast tumours. PMID- 7981443 TI - Monoclonal antibody BrE-3 participation in a multivariate prognostic model for infiltrating ductal carcinoma of the breast. AB - Monoclonal antibody (MoAb) BrE-3, an anti-human milk fat globule (HMFG) MoAb, is used here as a novel prognostic indicator for survival and relapse time in patients with infiltrating ductal carcinoma of the breast. A scoring system (4 Score method) was developed to this effect that measured, in a statistically reliable fashion, the level of expression of the epitope for MoAb BrE-3 in the cytoplasm and membranes of breast carcinoma cells in paraffin-embedded sections. In univariate analysis, data obtained by the 4-Score Method as well as data from traditional prognostic indicators (tumor size, axillary node status, and grade of differentiation) were found to be associated with patient survival and relapse. In multivariate analysis, using a Cox proportional hazards regression model, levels of expression of BrE-3 epitope plus tumor size and axillary node status were weighted and combined in an Individual Linear Composite Prognostic Score (ILCPS) that had a high level of association with survival and relapse time in this sample model of patients with infiltrating ductal carcinoma of the breast. This level of association was found to be higher than the level of association for any other combination of traditional or 4-Score method variables. The level of expression of BrE-3 significantly adds to the prognostic capacity of traditional prognostic markers for infiltrating ductal carcinoma of the breast. PMID- 7981446 TI - Oral contraceptive use and the prognosis of breast cancer. AB - In 471 breast cancer patients the influence of a positive history of oral contraceptive (OC) use on survival was investigated. 297 (63%) patients used OCs during any period of their life and 92 (20%) used them still at the time of diagnosis. Sixty months after diagnosis OC users had a significantly increased overall survival (p = 0.037). Survival rates amounted to 79.5% and 70.3% for OC users and non-users, respectively. The effect persisted after adjustment for other prognostic factors and was mainly attributed to women who had taken OCs four years or longer (p = 0.025). Comparing the survival after a 56 months median follow-up dependent on duration of OC use (never, 1-48 months, > or = 49 months) in subgroups of prognostic factors, the most significant influence on survival was observed among long-term users with tumors more than 2 cm in diameter (p = 0.005), with axillary node-positive tumors (1-3 nodes, p = 0.055/ > or = 4 nodes, p = 0.019), and with tumors of low estrogen receptor (p = 0.015) or progesterone receptor content (p = 0.04). The difference in survival between OC users and non users cannot be explained by the distribution of prognostic factors investigated (histological type, histological grade, tumor size, lymph node involvement, hormonal receptor content). OC users had an even higher percentage of poorly differentiated tumors (p = 0.003). These results suggest an effect of OC use on tumor biology during the preclinical phase of the disease. PMID- 7981444 TI - Prevalence of aneuploidy, overexpressed ER, and overexpressed EGFR in random breast aspirates of women at high and low risk for breast cancer. AB - Breast tissue biomarkers which accurately predict breast cancer development within a 10 year period in high risk women are needed but currently not available. We initiated this study to determine 1) the prevalence of one or more breast tissue abnormalities in a group of women at high risk for breast cancer, and 2) if the prevalence of biomarker abnormalities is greater in high risk than in low risk women. Eligible high risk women were those with a first degree relative with breast cancer, prior breast cancer, or precancerous mastopathy. Low risk women were those without these or other major identifiable risk factors. Ductal cells were obtained via random fine needle aspirations and cytologically classified. Biomarkers included DNA ploidy, estrogen receptor (ER), and epidermal growth factor receptor (EGFR). The prevalence of DNA aneuploidy was 30%, overexpression of ER 10%, and overexpression of EGFR 35%, in the 206 high risk women whose median 10 year Gail risk (projected probability) of developing breast cancer was 4.5%. The prevalence of aneuploidy and overexpressed EGFR was significantly higher in the high risk women than in the 25 low risk controls (p < 0.002), whose median 10 year Gail risk was 0.7%. The difference in the prevalence of ER overexpression between high and low risk groups was not statistically significant (p = 0.095). This may be due to the low prevalence of overexpressed ER and the small number of controls. A significant difference was noted in the prevalence of one or more abnormal biomarkers between the high risk and low risk women (p < 0.001). A large prospective trial is needed to determine if one or more of these biomarkers, is predictive of breast cancer development. PMID- 7981445 TI - Analysis of epidermal growth factor receptor mRNA expression by polymerase chain reaction assay in 94 human breast adenocarcinoma tumors. AB - It is well known that breast cancer cells can synthesize and secrete various growth factors that are able to stimulate tumor growth through autocrine and/or paracrine mechanisms. EGF is one of these growth factors involved in normal breast epithelial development and tumor proliferation. EGF and TGF alpha (EGF like peptide) are produced in variable amounts and both bind to the EGF receptor (EGF-R). Previous investigation in the laboratory measuring free and occupied EGF R sites by differential ligand binding assays had demonstrated that non-occupied and total binding sites were present in 54 and 90% of 216 breast tumor biopsies respectively. EGF-R appeared to be totally masked by endogenous ligand in 40 and 21% of estrogen receptor positive and negative tumors respectively. The aim of the present study was to check by a molecular method the expression of the EGF-R gene. The PCR method was applied to 94 tumor samples of the previous series. Total RNA was treated with 0.5 units of Rnase-free Dnase/mg of RNA to remove any contaminating DNA. We simultaneously reverse transcribed and amplified another transcript (beta-actin) as an internal standard. Both signals were present in 88 of the 94 samples while the presence of EGF-R was detected in 74 of them when assessed by radioligand assay. The findings indicate that 93% of the tumors analysed in this series expressed EGF-R mRNA, in agreement with our previous data on occupied EGF-R sites, i.e. two-fold more than by using the standard binding assay. No significant correlation was observed between the expression of the EGF R gene and the estrogen receptor content. PMID- 7981447 TI - Tumor markers in patients with advanced breast cancer as prognosticators: a preliminary study. AB - A retrospective study was performed on 69 breast cancer patients (stage II, N = 18; advanced disease, N = 51) in order to assess the prognostic value of circulating prolactin (PRL), CEA, CA 15-3, insulin-like growth factor-1 (IGF-1), and epidermal growth factor (EGF) by RIA/IRMA. These markers were compared with short-term prognosis (two years). Significant difference was observed only for PRL ( < 20.0 ng/ml vs. > 20.0 ng/ml), which provide an independent predictor of short-term prognosis in advanced breast cancer. PMID- 7981448 TI - Comparison of estrogen and progesterone receptor status to lymphocyte immunity against tumor antigens in breast cancer patients. AB - Estrogen (ER) and progesterone receptor (PgR) content of tumors were determined by both the dextran-coated charcoal (DCC) cytosol and immunocytochemical assays (ICA), and these hormone receptor results were compared to lymphocyte immunity against tumor antigen(s) for 52 breast carcinoma patients. Hormone receptor analysis by both methods demonstrated that 60% of the patients' tumors had ERs, while 44% were positive for PgRs. The ICA procedure was more sensitive than the cytosol technique for determining PgR content of the tumors. This increased sensitivity was not observed for ER by ICA. Patient age, tumor size, and nodal status were not related to the ER and PgR receptor status. A total of 21/52 (40%) of the patients had positive lymphocyte immunity against tumor antigen. This immunity was independent of patient age, tumor size, and nodal status. There was no significant relationship between lymphocytic immunity against tumor antigen and ER or PgR content of tumors, suggesting that patient lymphocyte immunity against tumor is independent of hormone receptor status. This is further evidence that lymphocyte immunity against tumor antigen status is an independent prognostic indicator that may be useful in the selection of a subset of node negative patients for adjuvant chemotherapy. PMID- 7981449 TI - Relationship of serum and tumor levels of iron and iron-binding proteins to lymphocyte immunity against tumor antigen in breast cancer patients. AB - Fifty-two breast cancer patients were evaluated for levels of several molecules related to iron metabolism including determining their tumor tissue and serum ferritin levels, serum transferrin levels, and serum iron levels. In addition the patients' lymphocyte immunity against autologous tumor antigen was investigated. Forty percent (21 of 52) of the patients had lymphocyte immunity against tumor antigen. Iron metabolism molecules were expressed in abnormal quantities in some breast cancer patients: 27% (13 of 49) had elevated tumor tissue ferritin levels, 4% (2 of 49) had abnormally high serum ferritin, 10% (5 of 49) had abnormally low serum transferrin levels, and 43% (21 of 49) had depressed serum iron levels. None of these abnormalities in iron metabolism are associated with tumor immunity. These iron metabolism molecules may be indicative of rates of cell proliferation or may influence growth of breast cancer cells, but do not appear to influence host lymphocyte immunity against tumor associated antigens. PMID- 7981450 TI - Protein S and protein C level changes with adjuvant tamoxifen therapy in postmenopausal women. AB - Tamoxifen citrate is a synthetic antiestrogen that provides survival benefit when given as adjuvant treatment in postmenopausal women with breast cancer. Venous thrombophlebitis may complicate tamoxifen treatment at a rate of approximately one per 800 treatment-years. To explore the possible procoagulant effects associated with tamoxifen therapy we evaluated changes in protein S and C activity levels in 58 postmenopausal women with surgically resected breast cancer who were disease-free and participating in a double-blind, placebo-controlled, randomized toxicity study of tamoxifen. The changes in protein C activities for the tamoxifen group (mean level = 113%) compared to those in the placebo group (mean level = 115%) were not significant (p = 0.45). Protein S activity levels increased while protein C activity levels decreased from baseline at 24 months in both tamoxifen and placebo groups. We conclude that the possible thrombophlebitis promoting effect of tamoxifen in postmenopausal women is unlikely to be explained on the basis of protein S and protein C activity level changes. PMID- 7981452 TI - Characterization of tamoxifen stimulated MCF-7 tumor variants grown in athymic mice. AB - The non-steroidal antiestrogen tamoxifen (TAM) is successfully used to treat all stages of breast cancer in both pre- and postmenopausal women. Unfortunately, most women treated with TAM eventually develop resistant tumor recurrences which require intervention with a second-line endocrine therapy, or cytotoxic chemotherapy if the recurrence is completely endocrine insensitive. There is evidence that some recurrences may in fact be TAM stimulated. MCF-7 human breast cancer cells grown as solid tumors in athymic mice chronically treated with TAM reproducibly develop a TAM stimulated phenotype (Osborne et al., Eur J Cancer Clin Oncol 23:1189-1196, 1987; Gottardis and Jordan, Cancer Res 48: 5183-5187, 1988; Osborne et al., J Natl Cancer Inst 83:1477-1482, 1991; Wolf et al., J Natl Cancer Inst 85:806-812, 1993). Tumors of this type may provide a useful model for a subset of therapeutic failures in the clinic. Therefore, we have extensively studied this model in an attempt to define the mechanism or mechanisms leading to TAM stimulated growth. In this paper we describe the characteristics of 4 TAM stimulated MCF-7 tumor variants. All of these tumors are growth stimulated by TAM, but vary in their response to estradiol (E2) treatment, and grow poorly in placebo treated hosts. All tumor variants express estrogen receptor (ER) RNA and protein, which at the RNA level appear to be down regulated by TAM, and to a greater extent by E2. All tumors also express epidermal growth factor receptor (EGFR) RNA, which is down regulated by TAM, and further down regulated by E2. However, among the tumor variants analyzed, ER and EGFR levels appear to be inversely related. Further, despite the expression of ER by all 4 TAM stimulated tumor variants, E2 induction of progesterone receptor expression is very weak or entirely absent. PMID- 7981453 TI - The estrogen receptor from a tamoxifen stimulated MCF-7 tumor variant contains a point mutation in the ligand binding domain. AB - The nonsteroidal antiestrogen tamoxifen (TAM) is the most commonly used endocrine treatment for all stages of breast cancer in both pre- and postmenopausal women. However, the development of resistance to the drug is common, as most patients treated with TAM eventually experience a recurrence of tumor growth. One of the potential mechanisms of treatment failure is the acquisition by the tumor of the ability to respond to TAM as a stimulatory rather than inhibitory ligand. We (Gottardis and Jordan, Cancer Res 48:5183-5187, 1988; Wolf et al., J Natl Cancer Inst 85:806-812, 1993) and others (Osborne et al., Eur J Cancer Clin Oncol 23: 1189-1196, 1987; Osborne et al., J Natl Cancer Inst 83: 1477-1482, 1991) have extensively described the reproducible development of TAM stimulated growth in a laboratory model system using MCF-7 human breast cancer cells grown as solid tumors in athymic mice. In this paper we report on the isolation of an estrogen receptor (ER) from a TAM stimulated tumor (MCF-7/MT2) which contains a point mutation that causes a tyrosine for aspartate substitution at amino acid 351 in the ligand binding domain. The mutant appears to the major form of ER expressed by this tumor. We also report that only wild type ER was detected in three other TAM stimulated MCF-7 tumor variants, suggesting that multiple mechanisms are possible for the development of TAM stimulated growth. The implications of these findings are discussed. PMID- 7981451 TI - Studies of tamoxifen as a promoter of hepatocarcinogenesis in female Fischer F344 rats. AB - Tamoxifen, an antiestrogen used in the treatment of breast cancer, was assessed for carcinogenic potential in the two-stage model of experimental hepatocarcinogenesis. Groups of female Fisher F344 rats were initiated with a non necrogenic, subcarcinogenic dose of diethylnitrosamine (DEN; 10 mg/kg, po) and fed tamoxifen at a concentration of 250 mg per kg of AIN-76A diet for 6 or 15 months. The livers of these animals exhibited an increase in size and number of altered hepatic foci compared with those animals which were initiated with DEN but not exposed to tamoxifen. This finding indicates that tamoxifen may have a carcinogenic potential in the rat liver. After 6 months of treatment, neoplastic nodules were observed in 3/8 rats in the DEN-initiated, tamoxifen-treated group. In the initiated group provided with tamoxifen for 15 months, neoplastic nodules were observed in 7/8 rats and hepatocellular carcinomas in 3/8 rats. The serum level of tamoxifen in these rats was 200-300 ng/ml. The ratio of tamoxifen, 4 hydroxy tamoxifen, and N-desmethyl tamoxifen was 1:0.1:0.5-1 in the serum. When adjusted for age-related weight increases, the serum and liver levels of tamoxifen and its N-desmethyl metabolite did not change over the 15 months. In the rat liver, the level of tamoxifen and its N-desmethyl metabolite was 10-29 micrograms/g liver after 6 or 15 months of chronic dietary administration. The ratio of tamoxifen:4-hydroxy tamoxifen:N-desmethyl tamoxifen was 1:0.1.3-3.3 in the liver. Therefore, the liver had 20- to 30-fold more tamoxifen and 4-hydroxy tamoxifen and at least 100-fold more N-desmethyl tamoxifen than the serum (assuming 1 gram of tissue is equivalent to 1 ml of serum). These results indicate that tamoxifen is a promoting agent for the rat liver at serum levels found in patients given the usual therapeutic course of tamoxifen. The high concentrations of tamoxifen attained in the rat liver indicate that actions other than its known estrogenicity for liver could contribute to its promoting action. In addition, these results indicate that the pharmacodynamic differences in tamoxifen metabolism in rats and humans and at low versus high doses should be determined. Thus, the therapeutic indications for tamoxifen should be balanced by the potential risk it may present as a promoting agent in mammalian liver. PMID- 7981454 TI - What do we know and what don't we know about tamoxifen in the human uterus. AB - Since its introduction in the early seventies, the list of indications for the use of the antiestrogen tamoxifen has been continuously expanded. Tamoxifen is now used for the treatment of metastatic breast cancer and for long-term and often indefinite administration as an adjuvant therapy. Large clinical trials in three countries are now evaluating the efficacy of tamoxifen as a preventive agent. However, tamoxifen therapy has been associated with an increased incidence of endometrial carcinoma. Laboratory and clinical data available to date on this controversial issue can be summarized as follows: a) Tamoxifen can have an estrogenic effect on endometrium in the presence of low estrogen levels. b) Tamoxifen treatment is probably associated with an increased incidence of endometrial cancer; however, this association appears to be linked to higher tamoxifen doses (40 mg/d). d) It is not known whether tamoxifen causes or allows the identification of occult endometrial carcinoma. e) At the present time there is evidence for a tumor promoting effect of tamoxifen on endometrial cancer at a dose of 20 mg per day. f) Replacement of tamoxifen by 'pure' antiestrogens or coadministration of progestins with tamoxifen do not appear to offer benefit unless clinical trials demonstrate a reduced incidence of endometrial problems. g) Patients must be evaluated for pre-existing endometrical carcinoma before starting tamoxifen therapy. f) Close followup of long-term tamoxifen patients with endometrial biopsies is recommended with individuals who experience symptoms. PMID- 7981455 TI - Molecular mechanisms of antiestrogen action in breast cancer. AB - The success of antiestrogen therapy to treat all stages of breast cancer, and the evaluation of tamoxifen as a preventive for breast cancer in normal women, have focused attention on the molecular mechanisms of antiestrogen action and mechanisms of drug resistance. The overall goal of research is to enhance current therapies and to develop new approaches for breast cancer treatment and prevention. Recent studies show that tamoxifen and the new pure antiestrogens appear to have different mechanisms of action: tamoxifen and related compounds cause a change in the folding of the steroid binding domain that prevents gene activation whereas the pure antiestrogens cause a reduced interaction at response elements and cause a rapid loss of receptor complexes. Tamoxifen treatment produces changes in the cellular and circulating levels of growth factors that could influence both receptor negative or receptor positive tumor growth and the metastatic potential of a tumor. These events may explain the survival advantage observed with tamoxifen therapy. However, the current therapeutic challenge is to avoid drug resistance during long-term tamoxifen therapy. Numerous explanations for drug resistance to tamoxifen have been suggested, including elevated estrogen levels, increased tumor antiestrogen binding sites, receptor mutations, and impaired signal transduction. However, it is probable that multiple mechanisms evolve to facilitate tumor survival. Most importantly, current research is examining mechanisms responsible for the beneficial actions of tamoxifen on bones and lipids as well as the potentially deleterious effects of tamoxifen on liver and endometrial carcinogenesis and retinopathy. The urgent need to understand antiestrogenic drug mechanisms and toxicity is being facilitated by the application of the technology developed for basic molecular biology. PMID- 7981456 TI - Alternative mechanisms of action of anti-oestrogens. AB - The molecular mechanism of action of anti-oestrogens such as tamoxifen appears to be a complex mixture of antagonism of the mitogenic action of oestradiol at the level of the oestrogen receptor, plus a range of other activities from enzyme inhibition to growth factor modulation. This article will concentrate on two specific areas: 1) the inhibition of protein kinase C and calmodulin-dependent cAMP phosphodiesterase; and 2) the regulation by tamoxifen of peptide regulators of breast cancer epithelial cell growth such as insulin-like growth factor I (IGF I) and transforming growth factor beta (TGF-beta). The elucidation of these mechanisms is potentially important in the treatment and chemoprevention of breast cancer-the quantitative contribution of each individual mechanism of the overall antineoplastic action of anti-oestrogens is central to developing new and possibly more effective anti-oestrogens and optimizing strategies for their use. PMID- 7981457 TI - Identification and management of the woman at increased risk for breast cancer development. AB - Multiple factors which increase a women's breast cancer risk have been identified. These range from conditions such as lobular carcinoma in situ which increase risk to relatively high levels, to reproductive factors such as nulliparity which are associated with only a small increase in risk. When determining an individual's risk, all her potential breast cancer risk factors must be considered. In order for risk information to be meaningful to a woman, risk must be expressed as absolute risk over a defined time interval since there is no uniform agreement on what risk level is high enough to require intervention. At present, careful follow-up or prophylactic mastectomy are the management options available for the woman at increased risk. The efficacy of follow-up including breast self exam, physician exams, and screening mammography for early detection of cancer in a high risk population is unknown. Prophylactic mastectomy, while highly effective, does not provide complete protection from breast cancer and is more radical than the surgery done for established cancer in many cases. Which of these options is chosen by an individual woman is dependent on how much risk she is willing to assume. PMID- 7981458 TI - Antiestrogen action and growth factor regulation. AB - The basis of the anti-proliferative action of antiestrogens is generally considered to be their ability to inhibit estrogen induced growth pathways by competitively inhibiting the binding of estrogen to the estrogen receptor. Recent data suggest that this may not be the entire story. Moreover, the cascade of events responsible for inhibition of mitogenesis after an initial interaction with the estrogen receptor is poorly understood. Multiple growth factor pathways operate in both normal and neoplastic estrogen/antiestrogen target tissues. While it is unlikely that any single pathway is pivotal, interactions of estrogen and/or antiestrogens with some of these pathways have been implicated in their proliferative effects. The exact molecular mechanisms remain unclear but autocrine, paracrine/juxtacrine, intracrine, and endocrine mediators or various combinations of them are likely to be involved in vivo. Super-imposed on this is the possibility that 'cross-talk' between intracellular signaling pathways may also be involved. Elucidation of such molecular mechanisms will be important with respect to design of novel antiestrogenic/antimitogenic drugs and alternative treatment strategies for both breast and uterine cancer. PMID- 7981459 TI - The Royal Marsden Hospital pilot tamoxifen chemoprevention trial. AB - A pilot randomised placebo controlled trial using tamoxifen in healthy women at increased risk of developing breast cancer, has been undertaken in order to evaluate the problems of accrual, acute symptomatic toxicity, compliance, and safety as a basis for subsequent large national multicentre trials designed to test whether tamoxifen can chemoprevent breast cancer. From October 1986 until June 1993, 2012 healthy women with an increased risk of developing breast cancer, usually because of a strong family history, were randomly allocated to receive tamoxifen 20 mgs/day or placebo for up to 8 years if possible. Accrual remained high in spite of extensive informed consent regarding potential risk. Acute symptomatic toxicity was low for participants on tamoxifen or placebo and compliance remained correspondingly high with a predicted 77% of women on tamoxifen and 82% of women on placebo continuing medication at 5 years. There was a significant increase in hot flushes (34% versus 20%) mostly in premenopausal women (p < 0.005), vaginal discharge (16% versus 4%, p < 0.005), and menstrual irregularities (14% versus 9%, p < 0.005). The requirements for hormone replacement therapy for women on tamoxifen or placebo were the same. Safety monitoring indicates no adverse anti oestrogenic effects of tamoxifen. There was no obvious effect of tamoxifen on bone mineral densities (single photon radial absorption). The fibrinogen and antithrombin III were both lowered, resulting in no observed detrimental effect on the ratio of these clotting factors. There was a significant reduction in the serum cholesterol maintained out to 5 years. Annual pelvic assessment using transvaginal ultrasound indicates an increased incidence of uterine fibromata and benign ovarian cysts.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7981460 TI - Droloxifene, a new antiestrogen: its role in metastatic breast cancer. AB - Droloxifene, a new antiestrogen, has theoretical advantages over tamoxifen based on preclinical data. These include higher affinity to the estrogen receptor, higher antiestrogenic to estrogenic ratio, and more effective inhibition of cell growth and division in ER positive cell lines, as well as less toxicity, including reduced carcinogenicity in animal models. Droloxifene also exhibits more rapid pharmacokinetics, reaching peak concentrations and being eliminated much more rapidly than tamoxifen. A phase II study compared droloxifene in dosages of 20, 40, and 100 mg daily in postmenopausal women with metastatic, or inoperable recurrent, or primary locoregional breast cancer who had not received prior hormonal therapy. Of 369 patients randomized, 292 were eligible and 268 evaluable for response. Response rates (CR + PR) were 30% in the 20 mg group, 47% in the 40 mg group, and 44% in the 100 mg group (40 mg vs 20 mg, p = 0.02; 100 mg vs 20 mg, p = 0.04; pooled 40 + 100 mg vs 20 mg, p = 0.01). Median response duration also favoured the higher dosages (20 mg group = 12 months; 40 mg group = 15 months; 100 mg group = 18 months). When adjusted for prognostic factors, time to progression was significantly better for the 100 mg (p = 0.01) and the 40 mg (p = 0.02) group compared to the 20 mg group. Droloxifene increased SHBG and suppressed FSH at all dosages and suppressed LH at the 40 and 100 mg dosages. These hormonal effects increased with increasing dosage. Short-term toxicity was generally mild, and similar to that seen with other antiestrogens. Droloxifene appears active and tolerable. It may have a particular role in situations in which rapid pharmacokinetics, or an increased antiestrogenic to estrogenic ratio, are required. PMID- 7981462 TI - Complications of neonatal extracorporeal membrane oxygenation. AB - From 1973-1985 to 1988 the average patient complications per case were 1.44 per case and significantly increased during 1990 to 1992 to 2.10 per case (Figure 3). During the same periods patient survival significantly decreased from 84% (1973 1985 to 1988, n = 2463) to 80% (1990 to 1992, n = 4005) (Figure 4). The association between total complication rates and survival rate was examined by regression analysis (Table 5). The correlation of patient complication rate and total complication rate with survival is highly significant; however, causality cannot be established. When comparing different entry criteria (Table 2) for incidence of mechanical and patient complications, no significant differences are apparent. This is not surprising since each of the entry criteria were designed to identify the same patient population. When premature neonates (> 35 weeks) were placed on ECMO, 36% of them had intracranial haemorrhage (ICH) with 62% mortality while only 12% of the neonates < 35 weeks had ICH and a 49% mortality. Similar findings were noted with low birthweight neonates (< 2.2 kg), 28% had ICH with 64% mortality while only 12% of the neonates > 2.2 kg had ICH with a 50% mortality. Selection criteria remain problematic for a variety of reasons. They cannot be viewed as absolute because of variability between centres. What represents likely 80% mortality in one centre may not apply to another. Historical controls are misleading because changing respiratory therapy strategies make historical populations difficult to compare. Also, once an ECMO centre becomes established, a more challenging group of patients will be attracted than previously was the case. Further, a single entry criterion cannot be generalized for all entry diagnoses. Criteria for an 80% predicted mortality is probably not the same for MAS, CHN, PPHN, and sepsis. Subsequent patients registered in the Neonatal ECMO Registry of the Extracorporeal Life Support Organization will address these issues more thoroughly, as specific details of the pre-ECMO condition and therapeutic strategies are collected. This collective review should help to identify trends which require reassessment of technique or patient management. PMID- 7981463 TI - Bloodless open-heart surgery in infants and children. AB - Between October 1984 and January 1993, seven children of Jehovah's Witnesses underwent corrective open-heart surgery for congenital defects, on cardiopulmonary bypass (CPB). Age at surgery ranged from three months to 6.5 years, and weight ranged from 4.2 kg to 23.2 kg, with two children weighing less than 10 kg. The principal cardiac anomalies were tetralogy of Fallot (two), double outlet right ventricle (one), subaortic stenosis (one), transposition of the great arteries and ventricular septal defect (one), atrial septal defect and congenital heart block (one), and congenital mitral regurgitation (one). Hypothermic CPB was used in all seven operations with crystalloid priming of the extracorporeal circuit. CPB was based on our standard perfusion protocols. All surgical procedures were done without the use of blood or blood products. The mean preoperative haematocrit (Hct) was 40.9% (range 31.0-47.8%). The mean lowest intraoperative Hct was 17.3% (range 15.0-24.3%), whereas the immediate post-CPB Hct was 19.6% (range 15.3-24.0%). The Hct progressively increased to 29.2% (range 21.0-34.2%) on the first postoperative day, and 32.3% (range 24.2-38.3%) at the time of discharge. There was no hospital mortality, and the mean hospital stay was 10 days (8-13 days). We report the safe repair of complex open-heart surgery in children, without blood transfusion, even in small infants. The successful management of these patients requires meticulous attention to surgical and perfusion technique, and sound postoperative management. PMID- 7981464 TI - The significant relationship between platelet count and haemorrhagic complications on ECMO. AB - Haemorrhagic complications, which occur in up to 35% of infants during extracorporeal membrane oxygenation (ECMO), often produce devastating sequelae. Although many complex factors interact to control haemostasis, platelet number and function has significant impact on the development of primary haemostasis. The optimum platelet count on ECMO, however, has not been defined. At our institution prior to August 1987, platelet counts were maintained at greater than 100,000/mm3. After August 1987, however, platelet counts of greater than 200,000/m3 were maintained. In a retrospective study, patients were randomly chosen from these two treatment periods: group 1--March 1986 to July 1987; and group 2--June 1988 to June 1989. The average platelet count, platelets administered, hours on ECMO, and bleeding complications were compared to each other and to the July 1992 ELSO Registry. There was a significant difference in average platelet counts between group 1 and group 2. However, the amount of platelets administered per kg per day was similar. There was a significant difference in overall bleeding complications between Group 2 (12%) and the ELSO Registry (35%) (p < 0.01). There was a trend towards decreased complications in all subgroups, although sample size precluded significance. We conclude that increasing platelet counts to greater than 200,000/mm3 decreases the overall bleeding complication rate. This advantage is achieved without a continuous need for increased platelet administration once the desired level is reached and without an increase in perfusion time, mechanical complications, or mortality. PMID- 7981461 TI - Antiestrogen regulation of cell cycle progression and cyclin D1 gene expression in MCF-7 human breast cancer cells. AB - The molecular mechanisms by which antiestrogens inhibit breast cancer cell proliferation are not well understood. Using cultured breast cancer cell lines, we studied the effects of antiestrogens on proliferation and cell cycle progression and used this information to select candidate cell cycle regulatory genes that are potential targets for antiestrogens. Under estrogen- and serum free conditions antiestrogens inhibited proliferation of MCF-7 cells stimulated with insulin. Cells were blocked at a point in G1 phase. These effects are comparable with those in serum- and estrogen-containing medium and were also seen to a lesser degree in nude mice bearing MCF-7 tumors. Similar observations with other peptide mitogens suggest that the process inhibited by antiestrogens is common to estrogen and growth factor activated pathways. Other studies have identified G1 cyclins as potential targets for growth factor and steroid hormone/steroid antagonist regulation of breast epithelial cell proliferation. In MCF-7 cells growing in the presence of fetal calf serum, cyclin D1 mRNA was rapidly down-regulated by steroidal and nonsteroidal antiestrogens by an apparently estrogen receptor mediated mechanism. Cyclin D1 gene expression was maximally inhibited before effects on entry into S phase and inhibition was therefore not merely a consequence of changes in cell cycle progression. Together with data on the effects of antiestrogens in serum-free conditions [1], these results suggest down-regulation of cyclin D1 by antiestrogens may be a general phenomenon in estrogen receptor-positive breast cancer cells, independent of culture conditions and class of antiestrogen. These observations are compatible with the hypothesis that reductions in cyclin D1 levels may mediate in part the action of antiestrogens in blocking entry of cells into S phase. PMID- 7981465 TI - Lipid peroxidation in open-heart surgery. AB - Production of oxygen free radicals and subsequent lipid peroxidation are thought to occur during cardiopulmonary bypass (CPB) and myocardial ischaemia-reperfusion injury. Malondialdehyde (MDA), a lipid peroxidation product, was measured simultaneously in arterial and coronary sinus blood before CPB and after release of the aortic crossclamp. Additional arterial samples were drawn pre-, per-, and postoperatively. Thirteen patients scheduled for coronary artery and/or valvular surgery were studied. Cold, crystalloid, cardioplegic arrest (54 [35-120] minutes, median [range]) was induced retrogradely. Preoperatively, arterial MDA was 0.78 +/- 0.4 (mean +/- SD) mumol/l, and increased during CPB (highest level 3.66 +/- 1.08 mumol/l, p < 0.002, 30 minutes after the start of reperfusion). Arterial MDA was still increased four hours after the end of CPB (3.17 +/- 0.88 mumol/l, p < 0.003), but had returned to normal the first postoperative day. No difference was found between arterial and coronary sinus samples at any time. In conclusion, MDA increased in arterial blood during CPB, indicating that lipid peroxidation occurred. There was no intracoronary release of MDA during reperfusion of the ischaemic heart. PMID- 7981466 TI - A simple, safe and economical method for administration of continuous warm blood cardioplegia. PMID- 7981467 TI - Hormonal response to fluid administration in cardiac surgery patients. PMID- 7981468 TI - The neurobiology of infant-parent interaction in the newborn: an introduction. PMID- 7981469 TI - A neural circuitry analysis of maternal behavior in the rat. AB - This article reviews work that shows that the medial preoptic area of the hypothalamus plays a crucial role in controlling the occurrence of maternal behavior in rats. A primary goal of this report is to fit the medial preoptic area into a larger neural circuitry, examining its critical inputs and outputs. Lesions of the medial preoptic area disrupt maternal behavior and estradiol and prolactin injections into this region activate maternal behavior. The medial amygdala, which is located in the limbic telencephalon, sends a neural projection to the preoptic region. Research indicates that this projection influences maternal behavior by relaying olfactory input to the medial preoptic area. The output of the preoptic area influences maternal behavior through descending projections to the brain stem. One of the influences of such projections might be to regulate neural circuits involved in controlling specific maternal responses, such as retrieval (carrying of pups) behavior. PMID- 7981470 TI - Maternal behaviors: evidence that they feed back to alter brain morphology and function. AB - We review evidence suggesting that the brain of maternally behaving rats is altered as a result of the behavior of the animal towards her pups. Morphological changes seen in the supraoptic nucleus, which contains oxytocinergic neurons important for lactation, are observed not only in parturient, lactating animals but also in virgin animals induced by the presence of rat pups to behave maternally. The supraoptic nuclei of lactating and maternally behaving virgin animals have a higher incidence of dendritic bundling relative to non-maternal virgin animals. Also, stimulation of the lateral olfactory tract in in vitro brain slices elevates electrotonic coupling among supraoptic neurons only in maternally behaving animals and not in male or non-maternal virgins. In general the evidence presented supports the idea that maternal behavior in lactating and non-lactating animals, can have profound effects on the morphology and physiological functioning of oxytocinergic neurons in the hypothalamus. PMID- 7981471 TI - Psychobiology of maternal behavior: contribution to the clinical understanding of maternal behavior among humans. AB - Psychobiological studies of maternal behavior among non-primate mammals have arrived at several general conclusions that may aid in our understanding of human maternal behavior and in the clinical treatment of parenting disorders. The hormonal basis of maternal behavior arises during pregnancy and consists of a hormonal priming phase, extending over most of pregnancy, and a hormonal triggering phase at the end of pregnancy. Hormonal priming in several species depends upon estrogen, progesterone and prolactin, and hormonal triggering depends upon a decline in progesterone and an increase in estrogen, prolactin and oxytocin in different species. The onset of maternal behavior is hormonally based but postpartum maternal behavior in several species is based upon the stimulation that the mother receives from her young (i.e. is non-hormonally based). There is a transition period between these two phases soon after parturition during which contact with the young plays a crucial role in the maintenance of maternal behavior. The onset of maternal behavior may be viewed as the resolution of conflict between approach and withdrawal responses of females to their offspring. PMID- 7981472 TI - The role of lactogenic hormones in maternal behavior in female rats. AB - Most mammals display an immediate onset of maternal care towards their offspring at parturition. In contrast, inexperienced, nulliparous females are often slow responders and show less intensity in their maternal responses. The transition from a slow responder in non-parous females to a rapid response at parturition is facilitated by the endocrine state of pregnancy. The present report reviews recent evidence from my laboratory demonstrating a role for prolactin in the stimulation of maternal behavior in the rat and presents new findings suggesting tht the conceptus, through its secretion of placental lactogens, helps prime the maternal brain (one site being the medial preoptic area) to respond maternally at parturition. PMID- 7981473 TI - Brain opioids and mother-infant social motivation. AB - Brain opioids were the first neurochemical system to be implicated in the elaboration of social-bonding processes. Although a variety of neurochemical systems help elaborate social rewards and specific social behaviors, the role of opioids in the control of maternal behavior remains controversial. Although a great deal of data indicate that intermediate doses of morphine can reduce maternal behavior, the evidence, taken together, suggests that endogenous opioids promote the regulatory control of maternal behavior, probably by providing feedback concerning the satisfaction that can be had from indulging in various maternal behaviors. Thus opioid blockade with naltrexone can reduce maternal competence in animals, while at the same time increasing maternal motivation. Opiate blockade likewise appears to increase the social motivation of rat pups, but reduces the reinforcing quality of interaction with the mother, suggesting that opioids provide feedback concerning the pleasurable qualities of social interaction in both mothers and infants. The clinical implications of this knowledge are not straightforward, but they generally suggest that clinically deficient social bonding might be capable of being strengthened via manipulation of brain opioid systems. PMID- 7981475 TI - Influences of environmental demand on maternal behavior and infant development. AB - Research has shown that in conjunction with genetic factors, significant aspects of non-human primate development are influenced by the infant's physical and social environment. In addition to the direct impact of the environment on the infant, the infant's attachment relationship with the mother is seen as the primary mediating factor in shaping these influences. When the mother is able to cope with environmental demands, as a reflection of her responsivity to her infant's needs, she may prepare infants for periodic interruptions in her attention, ameliorate distress during disruptive periods and, most importantly, compensate for these disruptions with enhanced attention to her infant once they are ended. Our recent work shows that when the mother's survival requirements increase, and her coping capacities are exceeded, both short- and long-term deleterious effects on her developing offspring may emerge. Particularly when confronted with an unpredictable environment, mothers are less able to maintain effective, stress-buffering, maternal-coping mechanisms which can preserve a stable attachment relationship and permit normal infant development. When these coping mechanisms are insufficient, infants may show manifest disturbances, such as depression, during development or reveal more latent disturbances, such as reduced sociability and timidity, when psychologically challenged, even as young adults. Evidence now suggests that these long-term effects may, at least in part, be the product of altered neurodevelopment of the serotonergic and noradrenergic systems. PMID- 7981474 TI - Maternal behaviour in sheep and its neuroendocrine regulation. AB - Non-parturient sheep, hormonally primed and presented with newborn lambs are, at best, indifferent to them and if approached by the lamb may show violent rejection. However, non-gestant ewes primed with oestrogen and progesterone, but given vaginocervical stimulation, do show a rapid onset in maternal behaviour. This stimulation is ineffective in promoting maternal behaviour with epidural anaesthesia. Vaginocervical stimulation increases the release of oxytocin into cerebrospinal fluid and in-vivo microdialysis has revealed high levels of oxytocin release in limbic brain areas known to be important for maternal behaviour. Oxytocin, when given intraventricularly, produces the full complement of acceptance and suckling behaviour in non-gestant ewes. Although ineffective when given alone, opioids potentiate the release of oxytocin in the limbic brain and increase the intensity of maternal responding, while the opioid receptor blocker, naltrexone, prevents both maternal induction and oxytocin release. This neural basis for maternally motivated behaviour may be equally relevant to human behaviour, although the mechanisms available for addressing these peptidergic systems have clear differences. PMID- 7981476 TI - Milk as the proximal mechanism for behavioral change in the newborn. AB - Early experience in the context of suckling at the nipple is a crucial determinant of neurobehavioral development in mammals. In particular, milk has been recognized by developmental psychobiologists as an ecologically relevant sensory stimulus and should be viewed by clinicians as more than a source of nutrition in early human development. Gaining access to and processing milk during suckling serves as a primary focus of activity in the newborn. Because the rat fetus lacks prior exposure to milk or other suckling stimuli, it provides an excellent model system for investigating the development of milk-related responses. Fetal exposure to milk results in a cascade of behavioral, physiological and neurochemical consequences. Milk-induced activation of the endogenous opioid system plays an important role in reorganizing fetal motor activity, altering sensory responsiveness and supporting associative learning in the fetus. Subtle changes in contextual stimulation alter the ability of milk to engage different neurochemical systems. These findings suggest that the infant's first experiences with milk and other suckling stimuli may have lasting consequences for neurobehavioral development. PMID- 7981477 TI - Behavioral and physiological consequences of suckling in rat and human newborns. AB - Suckling, in addition to yielding milk, water and calories, exerts profound behavioral effects on newborn rats and humans. In particular, suckling induces feelings of calm, reduces heart rate and metabolic rate, causes infants to bring their hands to their mouths and elevates the pain threshold. These changes are mediated by opioid and non-opioid systems, each having its own separate behavioral and neurological characteristics. The implications of suckling-induced changes for long-term motivational and cognitive change are discussed. PMID- 7981478 TI - Learning as adaptation of the infant. AB - The present report advocates an adaptive, ecological approach to the study of learning in infants. Concepts of developmental niche and ontogenetic adaptation are applied to early mammalian development. Within this conceptual framework, it is asserted that learning cannot be fully understood separately from a behaving body; that learning is a dimension of behavior and physiology. The role of learning in the development of ingestive behavior, especially suckling and the transition to solid food, is used to illustrate the potential of studying learning in development. These considerations are offered as examples of an alternative approach to the empirical study of learning by infants. The approach advocated herein can be applied to clinical issues: developmental adaptations evolved in contexts that differ from our modern environments. Exposure to contexts or contingencies that are evolutionarily unexpected may inadvertently create pathology. PMID- 7981479 TI - The role of mother's voice in the organization of brain function in the newborn. AB - Newborn infants prefer the sound of the maternal voice within the first two days after birth. This early preference may be based on prenatal experience. The mother's voice is reported to be the most intense acoustical signal measured in the amniotic environment. Data showing the ability of the newborn to demonstrate voice preferences are presented. We have also investigated the response of the perinatal autonomic nervous system to speech sound stimulation. Both the newborn and fetus show heart rate decelerations in response to speech sounds. This cardiorespiratory attentional response occurs during sleep when sensory stimulation is probably influencing perinatal brain development. Early experience with voice has both acute and enduring effects on the developing brain. These effects have ramifications for the development of the auditory system, as well as for later social and emotional development. Further speculation and discussion on the form, function and assessment of newborn responsiveness to voice will be offered. PMID- 7981480 TI - Early relationships as regulators of infant physiology and behavior. AB - In recent years, animal research has revealed a network of simple behavioral and biological processes that underlie the psychological constructs we use to define early social relationships. Hidden within the observable interactions of parent and offspring are sensorimotor, thermal and nutrient-based events which have unexpected and widespread regulatory effects on infant behavior and physiology. The complex pattern of responses resulting from early separation in infant rats can be traced to the abrupt withdrawal of a number of discrete, independent regulatory processes which had been acting on individual components of the infant's physiology and behavior. These regulatory processes also appear to mediate long-term shaping effects exerted by early relationships, for example, on the vulnerability of the adult rat to hypertension and stress ulcer. In human development, early regulatory interactions may provide a bridge between biological and psychological processes in the development of our earliest mental representations. PMID- 7981481 TI - Sleep and arousal, synchrony and independence, among mothers and infants sleeping apart and together (same bed): an experiment in evolutionary medicine. AB - Although solitary sleeping in infancy is a very recent custom, limited to Western industrialized societies, and most contemporary people practice parent-infant co sleeping, virtually all laboratory research on sleep in human infants assumes that solitary infant sleep is the normal and desirable environment. We have used evolutionary and developmental data to challenge this view. We suggest that co sleeping provides a sensory-rich environment which is the more appropriate environment in which to study infant sleep. In addition, two preliminary, in laboratory, polygraphic investigations of mother-infant co-sleeping are reported in normal infants, within the peak age range for sudden infant death syndrome (SIDS). Five mother-infant pairs co-slept one night in the first study; in the second, three additional pairs slept separately for two nights and co-slept the third consecutive night. The results suggest that co-sleeping is associated with enhanced infant arousals and striking temporal overlap (synchronicity) in infant and maternal arousals, and that, possibly as a result, co-sleeping mothers and infants spend more time in the same sleep stage or awake condition. The implications of the hypothesis and preliminary results for research on the normal development of infant sleep and on SIDS are discussed. PMID- 7981483 TI - Pharmacological manipulations of the alpha 2-noradrenergic system. Effects on cognition. AB - Electrophysiological and neurosurgical lesion studies with experimental animals have implicated the ascending dorsal noradrenergic bundle of the locus coeruleus system in cognitive process such as memory, learning and selective attention. However, it has also been suggested that noradrenaline (norepinephrine) is crucial in certain cognitive functions associated with the frontal lobes, particularly the prevention of distractibility by irrelevant stimuli. The alpha 2 receptors of the prefrontal cortex appear to be of particular importance in this respect. Studies with humans and experimental primates provide substantial support for this view. The aged primate brain is prone to degeneration of the locus coeruleus, as well as profound catecholamine depletion in the prefrontal cortex, and so is ideal for psychopharmacological investigation of the role of noradrenaline in frontal lobe function. Elderly monkeys show deficits in performance of the delayed response task, which can be reversed directly by both the mixed alpha 1/alpha 2-agonist clonidine, the more specific alpha 2-agonist guanfacine and also, indirectly, by the alpha 2-antagonist yohimbine. It is suggested that these results can be explained by an attenuation of the distracting properties of irrelevant stimuli following stimulation of noradrenergic activity. Conversely, distractibility is magnified whenever noradrenergic activity is reduced. This is supported by similar findings in psychopharmacological studies of healthy humans. The exception to this is when the locus coeruleus is likely to be firing, e.g. in times of stress or when novel stimuli are encountered. Clonidine attenuates locus coeruleus firing on such occasions, and so counteracts any beneficial (or deleterious) effects of stress on task performance. alpha 2-Adrenoceptor agents have little therapeutic value in patients with dementia of the Alzheimer's type. However, they may have some clinical use in patients who have a cognitive symptomatology similar to that of patients who have received neurosurgical excisions to the frontal lobes, e.g. deficits in working memory, executive function or focused attention, with relative sparing of episodic short term memory. Patients with Korsakoff's disease, attention deficit disorder or schizophrenia may benefit from treatment with alpha 2-agents. In particular, idazoxan has putative therapeutic effects in patients with a neurodegenerative disorder, namely dementia of frontal type. PMID- 7981484 TI - Drug-induced parkinsonism in the aged. Recognition and prevention. AB - Drug-induced Parkinsonism is a frequent adverse effect of numerous drugs interfering with dopamine function at the basal ganglionic level. It accounts for 4% of all patients with Parkinsonism seen in neurology clinics. Pharmacological agents implicated in the production of this disorder have a wide range of applications in medicine, beyond the treatment of psychiatric illnesses. Antipsychotics, substituted benzamides and calcium channel blockers are the drugs most commonly involved. The aged population is at an increased risk of drug induced Parkinsonism due to intrinsic factors and because they often receive multiple drugs, including those from self-medication. Lack of knowledge in the medical profession of the potential hazards involved in the use of certain drugs plays a contributory role in the development of drug-induced Parkinsonism. Physicians should be always alert in order to detect, as early as possible, the presence of extrapyramidal symptoms in patients exposed to medications with antidopaminergic properties. Whenever possible, withdrawal of the medication will help resolve symptoms; complete remission takes place within 6 to 18 months in the majority of patients. The use of anti-Parkinsonian drugs is only advisable if the symptomatology is disabling. The best available treatment is prevention. PMID- 7981482 TI - Hypertension and age-related changes in the heart. Implications for drug therapy. AB - Heart disease in older individuals can be characterised as the result of 2 processes, hypertension and atherosclerosis, which are the major causes of heart failure in the elderly population. The aging heart undergoes changes at the molecular, cellular and organ levels. These age-related changes may then be modulated by pathological conditions, such as hypertension, and by the reduction of blood pressure. One characteristic of the aged heart is a limited capacity for adaptation, by hypertrophy, to increased mechanical load. This age-related attenuation of the hypertrophic response may be attributed to the diminished induction of proto-oncogenes such as c-fos, c-myc and c-jun. This diminution results from aging of the heart per se and may be modulated by extracardiac factors. With regard to the coronary vasculature, the age at which hypertension develops seems to be an important factor for determining the vascularity of hypertrophied hearts. Late-onset hypertension is not accompanied by coronary angiogenesis, and it decreases dilator reserve in spite of the absence of myocardial hypertrophy. In contrast, mechanical overload in infant hearts is accompanied by angiogenesis and normal dilator reserve. In principle, the normalisation of hypertension results in the regression of myocardial hypertrophy and decreased coronary dilator reserve. In aged hearts, it is not clear how hypertension-induced myocardial hypertrophy or coronary vascular changes regress. Although antihypertensive treatment is clearly associated with an improvement of cardiovascular mortality and morbidity in hypertensive elderly individuals, it remains unclear how treatments ameliorate the hypertension-induced alterations. PMID- 7981486 TI - Is ovarian cancer undertreated in older women? PMID- 7981485 TI - Idebenone. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic use in age-related cognitive disorders. AB - Idebenone is a benzoquinone compound which has been investigated in elderly patients with dementia. Its precise mechanism(s) of action remains unknown, but in vitro and in vivo studies suggest the drug may diminish nerve cell damage due to ischaemia, correct neurotransmitter defects and/or cerebral metabolism and facilitate memory and learning. In the small number of studies available for evaluation, idebenone was generally superior to placebo and comparable with bifemelane, oxiracetam and nebracetam on the basis of a number of objective and subjective tests and rating scales in patients with mild to moderate cognitive decline. Clinical trial results indicate that patients with mild dementia seem more likely to respond than those with greater functional decline. The degree of benefit conferred by idebenone is often difficult to determine, but in those who respond, improvement is generally mild to moderate. Therapy with idebenone appears well tolerated for up to 2 years, and no changes in vital signs or laboratory values have been seen in clinical trials. In view of the lack of a proven agent to limit or halt the progression of dementia in the elderly, idebenone may warrant consideration in patients with mild cognitive dysfunction on the basis of preliminary evidence of predominantly mild improvement of functional status in some patients and good tolerability. However, further well designed studies, including comparisons with newer and commonly used agents, such as tacrine, are required to better define the role of idebenone in this complex area of treatment. PMID- 7981489 TI - Effect of dietary fat on toad liver tumor induced by DMBA: ultrastructural studies. AB - Toads injected with 2 mg 7,12-dimethyl-benza(a)anthracene (DMBA)/toad, 3 times/week for 12 weeks induced liver tumors in 12 out of 50 cases. The electron micrograph of toad liver tumor showed disorganization of the rough endoplasmic reticulum which encircles or partially surrounds the mitochondria. Cristae mitochondrialis are rare in comparison with control. Enhancement of liver tumor incidences (29 out of 50 cases) by DMBA at the same dose level plus 2cc corn oil/toad, 3 times/week for 12 weeks was detected. Electronicrograph of this group showed the same criteria of malignancy as in the first group. No tumor incidences were detected in toads fed corn oil only. The electronmicrograph of liver cells showed a high increase in glycogen and lipid droplets. PMID- 7981490 TI - The contribution of cavernous body biopsy in the diagnosis and treatment of male impotence. AB - This study concerns the results of penile biopsies in 50 patients aged 27 to 80, with secondary impotence removed with a biopty gun or during penile surgery. The biopty gun specimens were equally representative as the open biopsy ones. The cause and the degree of erectile dysfunction were determined by clinical and laboratorial investigation. The histological study of the cavernous bodies in the patients with psychogenic impotence revealed normal erectile tissue. In patients with organic impotence, histological lesions were graded as mild, moderate or severe. The most severe lesions were observed in the erectile tissue and in particular in the smooth muscle of the trabeculae and the helicine arteries, which had been reduced and replaced by connective tissue. Histological lesions were found not only in the arterial but also in the venous leak cases. There was a correlation between their severity and the degree of impotence, although of no statistical significance. The penile biopsy determines the condition (state) of the functional cavernous smooth muscle tissue, the integrity of which is essential for the erectile mechanism as well as for the action of the vasoactive drugs and the results of vascular surgery. Its important role is evident as it contributes not only to the diagnosis of the cause, but also to the choice of treatment of male impotence. PMID- 7981488 TI - Hepatitis in nursing homes. Incidence and management strategies. AB - Due to improved sanitation and prevention of parenterally transmitted diseases, a trend towards a decreasing incidence of acute viral hepatitis has been observed in several countries in the last years. These changes in epidemiology affect elderly people in different ways, especially if they are residents of homes for the aged. The decrease of hepatitis A virus (HAV) infection in childhood has resulted in less antibody protection during adulthood and old age. This in turn has led to an increased risk of acute and severe hepatitis due to HAV infection, and/or community outbreaks even in elderly people. The spread of parenterally transmitted viruses, such as hepatitis B virus (HBV), hepatitis C virus (HCV) and hepatitis delta virus (HDV), occurs in homes for the aged, mainly through the common use of toiletries and nondisposable syringes. Improvement in hygiene standards has lead to a marked decrease of these infections. In conclusion, provided that the current hygiene standards are maintained, the risk of parenterally transmitted hepatitis viruses (HBV, HCV and HDV) in homes for the aged will be low. Paradoxically, the risk of enterically transmitted HAV may, in the near future, increase in wealthy institutions and/or in Western countries. PMID- 7981492 TI - Different effects of neurotensin and neuromedin-N on the proliferative activity of rat adrenal cortex. AB - Evidence indicates that neurotensin (NT) and neuromedin-N (NMN) exerts an adrenocorticotropic effect in the rat. The present study aimed to investigate whether these neuropeptides are able to stimulate the proliferation of rat adrenocortical cells in vivo and to compare their mode of action. Adrenocortical proliferative activity was assessed by the metaphase-arrest technique and metaphases were counted per medulla-containing adrenal section. A bolus administration of NT (3 micrograms/rat) resulted in a significant increase in the number of metaphases in both zona fasciculata and the entire cortex, an effect observed 48 h after the injection. The administration of NMN (3 micrograms/rat) induced a notable rise in the number of metaphases in the zona fasciculata and the entire cortex within 12 h, followed by a subsequent drop after 24 h and a return to normal values at 48 h. These findings indicate that NT and NMN enhance rat adrenal growth in vivo acting via different mediators. PMID- 7981491 TI - Possible role of brown adipose tissue as a mediator during cyclosporine-A treatment. AB - Cyclosporine-A (CsA) is a potent immunosuppressor used successfully to control rejection in organ transplantation. According to the most recent evidence, this drug modifies the lipid metabolism of the patient, provoking a rise in the blood lipids, constituting an important risk factor for acceleration of the atherogenic process. Taking into account that brown adipose tissue (BAT) constitutes the major storage site for cholesterol and triglycerides in the rat, and given the apparent lack of references about the implications of CsA on this tissue in the literature, we proposed to study the possible morphological changes occurring in BAT following the administration of this drug. Two groups of female Sprague Dawley rats were set up, the control group and a treated group in which each animal received subcutaneous injection of 5 mg/kg body weight/day of CsA. After 4, 11, 25 and 34 days of treatment, subgroups of animals were sacrificed and the brown adipose tissue removed was apportioned for subsequent microscopic assessment. The greatest degree of atypia and activity in the BAT was observed after administration of 11 doses of the drug, at which point there was a marked reduction in the cell size with loss of lipidic coalescence. With subsequent doses, the tissue slowly initiated a process of recovery. CsA also induced morphological changes in the BAT that, in the early stages of the study, appeared to be correlated with a lipolytic response of the tissue to the drug; thus, the BAT may be acting as a system to eliminate the excess of lipids in the blood provoked by CsA administration, while toward the end of treatment, there was a certain stability between the drug and the activity of the brown adipose tissue, and a tendency to reach a balance between lipolysis and lipogenesis. PMID- 7981487 TI - New platinum agents. A comparison in ovarian cancer. AB - Compared with most solid tumours in humans, ovarian cancer may be considered a relatively chemosensitive disease. The platinum-based drug, cisplatin, has significantly enhanced long term survival (by more than 10%), though there remains scope for considerable improvement. Carboplatin is equiactive with, but substantially less toxic than, cisplatin (especially in terms of nephrotoxicity, effects on the gastrointestinal tract and neurotoxicity). Long term data are emerging from randomised trials that support the replacement of cisplatin by carboplatin in the first-line treatment of ovarian cancer. Iproplatin is also less toxic than cisplatin, but is more toxic and less active than carboplatin. A further advance in reducing patient morbidity associated with platinum-based chemotherapy may come from the first orally administrable platinum complex, JM216, which has recently been introduced into clinical trials. Current and future platinum drug discovery initiatives should focus on circumventing mechanisms of tumour resistance to cisplatin. Laboratory studies have identified 3 major mechanisms of resistance: reduced drug transport, enhanced intracellular detoxification (through glutathione and/or metallothioneins) and enhanced DNA removal (or tolerance) of platinum-DNA adducts (the long assumed critical lesions leading to cell kill). Platinum complexes based on the 1,2-diaminocyclohexane carrier ligand (such as oxaliplatin and tetraplatin) have recently entered clinical trials, having been shown to circumvent cisplatin resistance in murine leukaemia tumour models. Clinically, they have shown little evidence of activity in cisplatin-resistant disease and appear to cause severe neurotoxicity. PMID- 7981493 TI - Subchronic toxicity of 3,3',4,4'-tetrachlorobiphenyl in the rat liver: an electron microscope study. AB - Ultrastructural effects of 3,3'4,4'-tetrachlorobiphenyl (PCB) congener #77 on the liver were evaluated following its feeding to Sprague-Dawley weanling rats. Treatment diets were prepared by dissolving the congener in 4% corn oil. Ten animals, either male or female, in each group were placed on the respective diets containing 10, 100, 1,000 and 10,000 ppb congener for 13 weeks. Ten animals of each sex served as the control that had only the oil added to the diets. In the congener-exposed animals the alterations consisted of a marked increase in the profiles of smooth endoplasmic reticulum, and in the heightened number of lipid droplets in many parenchymal cells. Several mitochondria showed abnormalities such as dumbbell shapes, and in others, the cristae were oriented parallel to the long axis of the organelle. Peroxisomes were numerous in the 10 ppb group and apparently had increased numerically in the liver of animals from the higher dose groups. Females were notably more affected by the congener when compared to their male counterparts. The results indicated that the compound is mildly toxic, and alteration in structure and function can be noted at the lowest dose used (10 ppb congener exposure). It is concluded that congener #77 may be moderately toxic and it may affect the overall health of the exposed animal. PMID- 7981494 TI - Toxicity of 2,2',4,4',5,5'-hexachlorobiphenyl in the rat liver: an electron microscope study. AB - Morphological effects on the liver of Sprague-Dawley rats administered orally 2,2',4,4',5,5'-hexachlorobiphenyl (PCB), congener #153, were analyzed. Treatment diets were prepared by dissolving the congener in 4% corn oil. Ten animals of either sex in each group were placed on the respective diets that contained 50, 500, 5,000, or 50,000 ppb congener. Ten animals of each sex served as the control that had only the oil added to the diets. Thirteen weeks after the onset of dosing, the animals were euthanized and liver samples were obtained from the animals and prepared for electron microscopy. Animals exposed to the congener showed (in a dose-related manner) a marked increase in smooth endoplasmic reticulum profiles, and in the number of lipid droplets in many parenchymal cells. Mitochondrial abnormalities such as dumbbell shapes, and in others, the cristae that were oriented parallel to the long axis of the organelle were present. The magnitude of morphologic alterations did not reveal gender differences. The results indicate mild hepatotoxicity of the congener in the rat. PMID- 7981495 TI - Differentiation of human lymphocytes into nuclear vlimata by meiosis. The cytotoxic effect of calcium-activated neutral proteinase inhibitor. AB - Phytohaemagglutinin (PHA)-activated lymphocytes differentiated into nuclear vlimata (NVs) in vitro. Lymphocyte attachment was followed by formation and extrusion of cytoplasmic vesicles, nuclear elongation and fragmentation into NVs. NVs and cytoplasmic vesicles were detached and organized into large cell nodules in suspension. Immunocytochemistry showed that T-lymphocytes differentiated mainly to NVs while B-lymphocytes to buds. During differentiation there was a loss or gain of T-antigenicity by either mother or daughter cell. Cytogenetic analysis by chromosomal spreading and in situ techniques showed that NVs do carry chromosomes of hypodiploid or hypohaploid sets. NVs were the result of meiosis stimulated by PHA. A lymphocytic population exhibited diploidies attributed to mitosis or symmetrical meiosis and hypodiploidies, hypohaploidies attributed to meiosis. A comparison between NVs and spermatozoa was provided. The inhibitor of calcium-activated neutral proteinase (CANP-I) was cytotoxic to NVs without interfering with NV production. A model was proposed for the action of CANP-I which is a promising agent against autoimmune diseases. PMID- 7981496 TI - The selective anticancer activity of the endogenous inhibitor of calcium activated neutral proteinase. A histological, cytological and chemosensitivity study. AB - The cytotoxicity of an endogenous inhibitor of calcium-activated neutral proteinase (CANP-I) was evaluated using various mammalian tumor-derived cell lines and human cell cultures. The inhibitor was selectively cytotoxic to human tumor cells from lung, bladder, melanoma and chronic myeloid leukemia tissues, in a dose-dependent manner, and was also cytotoxic to Walker rat tumor cells. The inhibitor was not cytotoxic to normal human, urothelial, fallopian tube, liver and resting white blood cells. Cytological examination of the treated malignant cells revealed cells with vacuolated cytoplasm, pyknotic, hyperchromatic nuclei and membranous, granular haematoxylinophilic extracellular matrix. The use of the inhibitor on urothelial tumor tissues caused great exfoliation of necrotic cells while not affecting normal urothelial tissues. When the inhibitor was tested on mixed cell cultures, consisting of normal and malignant cell clones, a selective cytotoxicity to the malignant cells occurred allowing the normal cells to grow unaffected. Cytogenetic and cytological examination of the remaining cells, after the inhibitor treatment, showed normal diploid karyotype and morphology. The inhibitor was also tested in vivo on Wistar rats bearing Walker tumors. Treatment with 50 Units/100 g i.p. daily for 5 days caused 90% tumor regression and necrosis of metastatic foci in the liver and abdomen, without toxic side effects. The protease inhibitors trypsin-chymotrypsin, aprotinin, leupeptin and E64 were also tested in vitro and showed no anticancer activity. In conclusion, the endogenous inhibitor of CANP selectively killed malignant cells of different chromosomal abnormalities, tissue and species origin; also nuclear vlimata and chemoresistant cells.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7981497 TI - Fine structure of the tapetum lucidum in the short-tailed stingray (Dasyatis brevicaudata). AB - The tapetum lucidum of the short-tailed stingray (Dasyatis brevicaudata) is located in the choroid of the superior fundus immediately external to the choriocapillaris. In this species the tapetum consists of a single layer of overlapping cells oriented at an angle of about 30 degrees to the incoming light. These tapetal cells alternate with and are separated from one another by melanocytes which extend beyond the tapetal cells to intervene between the tapetal cells and the choriocapillaris. The tapetal cells and the melanocytes are flattened plate-like cells with their widest dimension facing the retina. Internally the tapetal cells display a peripherally located vesicular nucleus with most organelles in a paranuclear location. The bulk of the cell is packed with regularly spaced crystals reported to be guanine. The size and spacing of these reflective crystals is commensurate with constructive interference. In light-adaptation, the melanosomes of the intervening melanocytes are widely dispersed and for the most part block the passage of light to the tapetal cells. Although dark-adapted specimens were not examined, it seems reasonable to assume that in dark-adaptation, the melanosomes will retreat to unmask the tapetum and allow it to function as a reflective layer. PMID- 7981498 TI - Retinal pigment epithelial fine structure in the short-tailed stingray (Dasyatis brevicaudata). AB - The retinal pigment epithelium (RPE), choriocapillaris and Bruch's membrane (complexus basalis) have been studied by light and electron microscopy in the short-tailed stingray (Dasyatis brevicaudata). The RPE consists of a single layer of cuboidal cells which display numerous basal (choroidal) infoldings as well as many apical (vitreal) processes which interdigitate with photoreceptor outer segments. The lateral cell borders are relatively smooth and joined by a series of tight junctions. Within these epithelial cells, smooth endoplasmic reticulum is the dominant organelle with only scattered profiles of rough endoplasmic reticulum. Polysosomes, mitochondria and phagosomes are abundant. Melanosomes are totally absent over the tapetum and are scarce in non-tapetal locations. The RPE nucleus is large, vesicular and centrally located. Bruch's membrane is a pentalaminate structure. The choriocapillaris is a single layer of large capillaries. The endothelium of these capillaries is typically thin but only minimally fenestrated. PMID- 7981499 TI - Retinal photoreceptor fine structure in the short-tailed stingray (Dasyatis brevicaudata). AB - The fine structure of the retinal photoreceptors has been studied by light and electron microscopy in the short-tailed stingray (Dasyatis brevicaudata). The duplex retina of this elasmobranch contains rods and cones in a ratio of about 10:1. No multiple receptors were noted nor was a repeating or mosaic arrangement of the cones obvious. Only light-adapted specimens were studied but retinomotor movements of the photoreceptors were felt to be minimal or absent. The rods are large cylindrical cells with inner and outer segments of much the same diameter. Cones are short stout cells with a conical outer segment and a wider inner segment. Rod outer segment discs show peripheral incisures while cones do not. The inner segment of rods and cones are rich in organelles indicating much synthetic activity. The nuclei of rods and cones appear quite similar but cone nuclei are invariably at least partially protruded through the external limiting membrane which is formed by a series of zonulae adherentes between photoreceptor cells and Muller cells. The synaptic region of both rods and cones display both invaginated (ribbon) synapses and superficial (conventional) synapses. PMID- 7981500 TI - Pancreatic duct infiltration in the low-dose streptozocin-treated mouse. AB - The pancreatic-duct system was observed during the initial stage of type 1 diabetes in C57BL/6J mice rendered diabetic with low doses of streptozocin. Light microscopy revealed that the ducts located in close proximity to islets (islet ducts) were involved in the infiltrating process: inflammatory cells extended from the islets to these ducts. However, ducts that were located far from islets (non-islet ducts) were generally free from infiltration. Immunocytochemistry revealed that both islet ducts and non-islet ducts express MHC class II and ICAM 1 molecules: this positivity seems to be mainly expressed by elements infiltrating the connective layer or by endothelial of vessels surrounding ducts. Strong ICAM-1 positivity demonstrates that adhesiveness is widely represented in early diabetes in this animal model. At the ultrastructural level only a few endocrine elements were observed scattered within the epithelial layer and single infiltrating elements were rarely encountered within the connective layer of ducts. The existence of other sites of "activation" other than the islets of Langerhans, in this as well as in other animal models of types 1 diabetes, is consistent with the hypothesis of an initially more widespread and less specific process that later undergoes restriction. PMID- 7981501 TI - The pathology of the atrophy/hypertrophy complex (AHC) of the liver. A light microscopic and immunohistochemical study. AB - The term, atrophy/hypertrophy complex (AHC) of the liver, denotes a distinct combination of hepatic atrophy and hypertrophy occurring in situations of significant impairment of bile flow and/or portal or hepatic venous blood flow. In the lobes or segments concerned atrophy ensues, whereas areas not or less involved develop compensatory hypertrophy, resulting in a characteristic gross deformity of the organ and, in some instances, in rotation of the liver around a virtual hilar axis. As recognition and early detection of AHC have a strong implication on the treatment of several hepatobiliary diseases, adequate combined clinical, radiological and histopathological strategies have to be used in order to arrive at a correct diagnosis. The present investigation was designed to analyze the morphology of AHC in detail and to define lesion patterns having the highest predictive value. For atrophy, the following features were highly characteristic: 1) Advanced septal fibrosis with or without nodular change of parenchyma; 2) Biliary piecemeal necrosis with formation of vascular structures; 3) Ductular proliferations, frequently extending into septa and involving the parenchyma; 4) Capillarization of sinusoids with type IV collagen deposition in Disse's space; 5) Factor VIII-associated antigen expression by sinusoidal endothelia; 6) a seemingly paradoxical increase of proliferative activity of hepatocytes as based on PCNA staining. The severity of lesions in atrophy was related to the type of underlying disease, in that the changes were clearly more expressed in situations of longstanding obstruction due to benign disease. Using a set of well-defined morphological parameters, atrophy can be reproducibly distinguished from hypertrophy in biopsy material from AHC. PMID- 7981502 TI - Ultrastructural localization of calcium in neuromuscular junctions of smooth and skeletal muscles after aminoglycoside antibiotics treatment. AB - Aminoglycoside antibiotics are all capable of producing clinically significant neuromuscular paralysis. Since part of the mechanism of action of these antibiotics at neuromuscular junction is a calcium-dependent inhibition of acetylcholine release, so this experiment was carried out in vitro on both somatic (isolated rat phrenic-nerve hemidiaphragm) and autonomic neuro-effector transmission (guinea-pig ileum) using gentamicin and amikacin, to determine the calcium contents at this level. Electron microscopic observations on gentamycin- and/or amikacin-treated materials, using potassium pyroantimonate method suggest a reduction of internal calcium in nerve terminals of both preparations. PMID- 7981503 TI - High endothelial venules and cell adhesion molecules in B-cell chronic lymphocytic leukaemia and related low grade B-cell lymphoma/leukaemia: I. High endothelial venules and lymphocyte migration. AB - The high endothelial venule (HEV)-content and the lymphocyte migration index (LMI) of reactive lymph nodes and lymph nodes from patients with B-cell chronic lymphocytic leukaemia (B-CLL), as well as some related B-cell malignancies (lymphocytic lymphoma -LL-, prolymphocytic leukaemia -PLL-) were determined and statistically analyzed. The HEV-content and the LMI were significantly higher in reactive lymph nodes than in the low grade B-cell lymphomas and leukaemias (p < 0.001). The number of HEVs among lymphoma/leukaemia cases was the highest in LL independently of the maturation. However, the maturation of the process seems to determine the intensity of lymphocyte migration; i.e. a significantly higher LMI was found in mature (B-CLL, PF, mature; M and LL, M) than in immature subtypes (B CLL, PF, immature -IM-; diffuse -D- and LL, IM) subtypes (levels of significance varied from p < 0.05 to p < 0.001). Based on these findings, a more intense migration of lymphocytes from blood to peripheral lymph nodes may be supposed in LL than in B-CLL, thus explaining the nodal sites of involvement in LL and the peripheral blood in B-CLL. Within the same histological categories the morphometric features in mature subtypes may implicate an enhanced HEV-lymphocyte interaction when compared to the immature subtypes. PMID- 7981504 TI - Neuroblastoma. A study of the clinicopathological features influencing prognosis based on the analysis of 54 cases. AB - The retrospective analysis of 54 cases of neuroblastoma taken from the files of the Department of Pathology, University of Santiago Hospital, Spain, and the Ludwig-Aschoff Institute of Pathology, University of Freiburg, Germany confirmed the validity and significance of various clinical and histopathological features when trying to establish the prognosis and the proper therapeutic approach in a given case of neuroblastoma. When the age of the patients was compared to survival it was shown that all but three of the patients older than 2 years of age had died from tumor within ten months. In contrast, there was a 37.5% five year survival rate among patients who were 24 months of age or younger at the time of diagnosis and treatment. The primary tumor was located in the adrenal gland in 27 cases (50%), in 9 cases (17%) the tumor was retroperitoneal but extra adrenal, and in the remaining 18 patients (33%) the tumor arose from the paravertebral sympathetic ganglia. Adrenal primaries behaved in an extremely aggressive manner as all but three patients with tumors at this location were dead within 18 months. Retroperitoneal extra-adrenal neuroblastomas followed an almost equally poor outcome with only one five-year survivor (11%). In contrast, 49% of the patients with paravertebral neuroblastoma had survived five years and a further 33% were alive with shorter follow-up. According to histological criteria, there were 6 grade I tumors, 15 grade II and 33 grade III tumors in our series. All grade I tumors were clinical stage I at diagnosis and all are alive 2 to 3 1/2 years later.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7981505 TI - Neuromedins and their involvement in the regulation of growth, structure and function of the adrenal cortex. AB - Current data on the synthesis and the mechanism of action of neuromedins on adrenal cortex are presented. The localization of these biologically-active peptides in all components of the hypothalamopituitary-adrenal axis as well as their action on the adrenal cortex both in vivo and in vitro suggest their involvement in the regulation of growth, structure and function of the adrenal cortex. Neuromedins may exert both direct and indirect effect on the adrenal cortex. Direct effect is proven by the stimulation of glucocorticoid synthesis by adrenocortical cells in culture (NMK, NML) while indirect effects may be mediated by ACTH, vasopressin (aldosterone secretagogue effect) and angiotensin (prompt proliferative response) or by substances of medullary origin. The last mechanism of action is well documented for NMU. PMID- 7981506 TI - Hypothalamocerebellar and cerebellohypothalamic projections--circuits for regulating nonsomatic cerebellar activity? AB - Cerebellar involvement in visceral and affective responses is known from physiological and behavioral studies, but the pathways involved in these responses have remained enigmatic. Over the last ten years neuroanatomical studies have shown that the cerebellum and hypothalamus are interconnected by direct hypothalamocerebellar and cerebellohypothalamic projections and by a multitude of indirect pathways. The hypothalamocerebellar projection terminates in the cerebellar nuclei and in all layers of the cerebellar cortex as multilayered fibres. This projection is, at least in part, histaminergic. New immunocytochemical experiments indicate that small numbers of hypothalamocerebellar neurones may contain GABA- or glycine-like immunoreactivity. GABA may function as a transmitter in hypothalamocerebellar fibres, probably in conjunction with histamine, but it is not clear whether glycine may also function as a transmitter or only serve metabolic functions. The bidirectional pathways between the cerebellum and hypothalamus may be part of the circuits through which the cerebellum participates in the modulation of a variety of nonsomatic events. In addition, new observations on patients with well localized cerebellar lesions reveal simultaneous somatic and visceral dysfunction. Recent research on direct hypothalamocerebellar pathways and on other connections between hypothalamus and cerebellum is reviewed. It is hypothesized that the cerebellum may act as a general modulator and coordinator of a wide range of central nervous activities, somatic as well as nonsomatic. PMID- 7981507 TI - Hirschsprung's disease--immunohistochemical findings. AB - Hirschsprung's disease (HSCR) is characterized by a non-propulsive distal intestinal segment (usually colon) leading to a functional obstruction. An absence of ganglia in the affected segment explains the synonymous term "aganglionosis coli". The lack of peristalsis is partly due to a deficient intestinal smooth muscle relaxation based on an absence of non-adrenergic, non cholinergic (NANC) inhibitory innervation. Morphological studies using conventional microscopy, immunohistochemistry and immunochemistry against general neuronal markers and neuropeptides have been used to characterize the disturbed NANC innervation in HSCR. An increased cholinergic and adrenergic innervation is registered in the aganglionic segment in spite of the lack of neuronal cell bodies: Neuropeptides like vasoactive intestinal peptide (VIP), pituitary adenylate cyclase-activating polypeptide (PACAP), gastrin-releasing peptide (GRP), calcitonin gene-related peptide (CGRP), substance P (SP), enkephalins and galanin immunoreactive nerve fibres are all reduced in number in the aganglionic segment. In contrast, neuropeptide Y (NPY)-containing nerve fibres are increased in number in the diseased segment, probably reflecting the adrenergic hyperinnervation. General neuronal markers including chromogranins have been used to map the neuronal network in the HSCR intestine and also to investigate the endocrine cell system in the intestinal mucosa. Nitric oxide is a potent component of the NANC inhibitory innervation and its synthesizing enzyme, nitric oxide synthase (NOS), is shown to be almost absent in the neuronal system in aganglionic intestine. PMID- 7981508 TI - Fast spin-echo MR imaging of the abdomen: contrast optimization and artifact reduction. AB - The effects of various fast spin-echo (FSE) magnetic resonance (MR) imaging parameters and artifact reduction techniques on FSE image contrast and quality were studied. The authors performed 139 abdominal MR examinations, comparing standard FSE images (echo train length [ETL] = 8, echo space [E-space] = 17 msec, bandwidth = +/- 16-kHz) with FSE images with an ETL of 16 (n = 22) or FSE images with a +/- 32-kHz bandwidth and an E-space of 11-14 msec (n = 22). FSE artifact reduction techniques were evaluated with spectral fat saturation (n = 40) or with a new flow compensation FSE sequence (n = 55). Images of liver lesions were reviewed qualitatively and with contrast-to-noise ratio (C/N) measurements. Decreasing the time of echo train sampling produced superior image quality, with increased anatomic sharpness, less image artifact, and improved liver-lesion C/N. Images obtained with an ETL of 16 showed more image blurring and a 23% decrease in relative contrast and 28% decrease in relative C/N for liver tumors. Increasing the bandwidth reduced E-space, producing a 12% decrease in background noise. Artifact reduction with fat saturation or flow compensation produced images with less ghosting artifact and superior overall image quality, with 39% and 20% increases in liver-tumor C/N, respectively. FSE image quality and contrast in the depiction of hepatic disease can be optimized with careful selection of imaging parameters and the use of artifact reduction techniques. PMID- 7981509 TI - Time after excision and temperature alter ex vivo tissue relaxation time measurements. AB - Previously unreported effects of tissue storage were recently observed in the authors' experimental magnetic resonance (MR) studies. To evaluate the effect of elapsed time after excision and storage temperature on tissue relaxation time measurements, tissue samples from the liver, pancreas, kidney, testis, spleen, and brain were obtained in rats. T1 and T2 were first measured within 5 minutes of excision, and between subsequent measurements, tubes were kept in a water bath at 40 degrees C, at room temperature (28 degrees C), or in an ice bath (4 degrees C). Cellular and organellar integrity was assessed with electron microscopy and correlated with the MR findings. At 40 degrees C (20-MHz spectrometer), the T1 of liver decreased from 280 msec +/- 8 to 212 msec +/- 10 during the first 60 minutes; the T1 of pancreas decreased from 276 msec +/- 3 to 208 msec +/- 2. Other tissues showed less than a 5% decrease in T1. T2 changes were smaller than T1 changes in all tissues. Electron microscopy of pancreatic acinar cells showed postmortem changes in mitochondria evolving over the first 60 minutes after death. Manganese loading experiments implicated mitochondrial manganese stores in the observed enhanced postmortem decrease in T1. This study calls into question reported relaxation time data for liver and pancreas. MR studies of excised tissues must account for time and temperature to prevent systematic experimental errors. PMID- 7981510 TI - Contrast-enhanced MR imaging of liver and spleen: first experience in humans with a new superparamagnetic iron oxide. AB - The aim of this prospective study was to obtain the first human safety and magnetic resonance (MR) imaging results with a new formulation of superparamagnetic iron oxide (SPIO) (SHU 555 A). The SPIO was tested at four iron doses, from 5 to 40 mumol/kg. Laboratory tests and clinical measurements were done in 32 healthy volunteers for up to 3 weeks after administration. MR imaging at 1.5 T was performed before and 8 hours to 14 days after fast intravenous injection (500 mumol Fe/min) of the SPIO (six subjects per dose). Results of this phase I study demonstrate that SHU 555 A at a concentration of 0.5 mol Fe/L was well tolerated. A dose-dependent minor increase in activated partial thromboplastin time, which remained within the normal range, was seen. All doses of SPIO caused a signal loss in both liver and spleen (P < .05) with a spin-echo sequence (TR = 2,300 msec, TE = 45 msec). The signal losses in the liver 8 hours after contrast agent injection were 58%, 79%, 82%, and 87% for the 5, 10, 20, and 40 mumol Fe/kg doses, respectively. The corresponding signal losses in the spleen were 23%, 45%, 65%, and 78%, respectively. The doses that reduced signal intensity by half were 3.1 mumol Fe/kg for the liver and 12.8 mumol Fe/kg for the spleen. The results suggest that the new SPIO formulation is a safe and efficient MR contrast agent. PMID- 7981511 TI - MR imaging detection of cerebral metastases with a single injection of high-dose gadoteridol. AB - The utility of a single high-dose (0.3 mmol/kg) injection of gadoteridol, a gadolinium chelate, in the detection of brain metastases on magnetic resonance images was studied. Patients (n = 29) with a high suspicion for brain metastases at clinical examination and by history were imaged on two occasions--separated by more than 24 hours and less than 7 days--with a 0.1 mmol/kg contrast agent dose used for the first study and a 0.3 mmol/kg dose for the second. In patients (n = 15) with confirmed brain metastases by clinical, radiologic, and/or histologic criteria, 40 lesions were detected at the 0.3 mmol/kg dose by a single reader blinded to contrast agent dose, compared with 33 lesions at 0.1 mmol/kg, a 21% increase. Three of 15 patients (20%) demonstrated an increase in the number of lesions detected at the higher dose. Region-of-interest analysis of signal intensity measurements showed that lesion contrast (relative to normal brain) improved from 54% at 0.1 mmol/kg to 92% at 0.3 mmol/kg. A 0.3 mmol/kg dose of gadoteridol, administered in a single injection, permits identification of brain metastases not detected at 0.1 mmol/kg. Such information can influence the choice of therapy. PMID- 7981512 TI - Metabolite concentrations in the developing brain estimated with proton MR spectroscopy. AB - The purpose of the present study was to estimate absolute concentrations and relaxation time constants of metabolites that were detectable with proton magnetic resonance (MR) spectroscopy in the healthy preterm, term, and infant brain. Five MR spectra were recorded for each infant by using STEAM (stimulated echo acquisition mode) sequences with different TEs and TRs. Water was used as an internal standard. The T1 of choline-containing compounds (Cho) and the T1 of phosphocreatine plus creatine (PCr+Cr) decreased. The T2 of the N-acetyl-L aspartate (NAA) resonance increased, probably because of a relatively larger signal overlap with glutamate in the most immature brains. The concentration of NAA almost doubled, whereas the Cho concentration showed only a nonsignificant tendency to decrease; therefore, the well-known increase in the ratio of NAA to Cho appears to be due mostly to an increase in NAA concentration. The concentration of PCr+Cr increased rapidly and reached adolescent values at approximately 4 months of age. PMID- 7981513 TI - Precise and accurate measurement of proton T1 in human brain in vivo: validation and preliminary clinical application. AB - Precise and accurate inversion-recovery (PAIR) magnetic resonance (MR) measurements of T1 were obtained in eight brain regions and cerebrospinal fluid of 26 healthy volunteers. Accuracy of the technique was assessed by measuring T1 in small fluid volumes with the PAIR technique and with two independent spectroscopic techniques. The mean difference between T1 measured with PAIR and with the two spectroscopic techniques was 3.1% +/- 1.3. The precision (reproducibility) of measurements with the PAIR technique was excellent. The coefficient of variation (CV) across 16 measurements in a head phantom was 2.0%, compared with a CV of 2.7% across 45 separate measurements in a single subject. The within-subject CV was 1.8% +/- 0.6 in white matter and 1.4% +/- 1.0 in basal ganglia. The between-subject CV in 26 healthy volunteers was 3.6% +/- 0.6 in white matter and 4.1% +/- 1.9 in basal ganglia. Comparison between a patient with an active recurrent brain tumor and an age-matched patient with an inactive brain tumor showed that T1 was significantly elevated throughout the brain of the active-tumor patient, especially in white matter tracts, even though no tumor or edema was detected in the white matter on standard MR images. Comparisons between five brain tumor patients and four healthy volunteers of similar age showed that T1 was significantly and substantially elevated throughout the white matter tracts and in the caudate nucleus, putamen, and thalamus. These results are consistent with the hypothesis that white matter tracts are selectively vulnerable to edema and that T1 increases in white matter are a sensitive indicator of patient status or tumor aggressiveness. PMID- 7981514 TI - Reproducibility of nonparametric feature map segmentation for determination of normal human intracranial volumes with MR imaging data. AB - Semiautomated segmentation of dual-contrast magnetic resonance images was used to determine volumes of total brain, gray matter, white matter, and cerebrospinal fluid (CSF) in healthy volunteers. Reproducibility of the technique was evaluated in terms of intraobserver, interobserver, and study-to-study variations. Intraobserver coefficients of variation ranged from 0.4% to 6.0%, while interobserver values ranged from 0.8% to 9.9%. In both cases, the maximum variations were obtained in volume measurements of tissues with maximum complexity (ie, CSF), and the minimum variation was obtained in determining total brain volume. This was also true in the case of study-to-study variations in volume measurements, for which the coefficients of variation ranged from 0.5% to 8.7%. The use of appropriate preprocessing techniques, which are crucial to the accuracy and reproducibility of the segmentation technique, are described in detail. PMID- 7981515 TI - A novel fast T1-mapping method. AB - The authors present a novel fast T1-mapping technique that allows a T1 map to be reconstructed from data acquired in less than 3 seconds. Data were acquired by using two modified TurboFLASH (fast low-angle shot) sequences and were processed with a combination of one-dimensional Fourier transforms and a parameter-fitting routine, instead of a standard two-dimensional Fourier transform. Apparent T1 (T1*) maps were obtained, from which T1 maps were calculated. Comparisons of T1 values obtained in phantoms and the human brain by using this technique with those obtained with multipoint inversion-recovery T1 mapping showed that the new method yielded accurate T1 values. Optimization of the method will further improve speed and accuracy. The general approach of this T1-mapping technique is believed to be also applicable to other problems, such as T2 and T2* mapping. PMID- 7981516 TI - Pulsation artifact in short TR MR imaging and angiography: exacerbation with signal averaging. AB - Averaging the signals from more than one excitation per phase-encoding view increases the signal-to-noise ratio and, in conventional spin-echo magnetic resonance imaging, reduces most motion artifacts. To determine the effects of signal averaging on two-dimensional gradient-echo images, acquisitions with different TRs and with no averaging versus multiple-signal averaging were compared in a pulsatile flow phantom and the human abdominal aorta. Intraview (each view repeated before changing the phase-encoding value) and interview (obtaining all views sequentially and then repeating the entire set) averaging methods were used. Pulsation artifacts were present on all images of the flow phantom and the aorta. Intraview signal averaging, the method most commonly used, exacerbated rather than ameliorated pulsation artifacts with short TR sequences. Pulsation artifacts on two-dimensional images obtained with a short TR can be minimized by completing the acquisition as rapidly as possible, avoiding signal averaging. If signal averaging is used for short TR images, it should be interview averaging. PMID- 7981517 TI - In vivo comparison of two through-plane MR velocity mapping methods: fast Fourier encoding and phase mapping. AB - Magnetic resonance imaging maps of velocity were acquired with a 1.5-T system in 10 subjects in a plane perpendicular to the main pulmonary artery. Velocity images were successively acquired with a method developed from Fourier-encoding velocity imaging (FEVI) principles with eight gradient steps and one excitation, and with two-point phase-subtraction mapping. Reconstruction in FEVI was implemented by zero-filling interpolation around the eight gradient steps and then around the four central steps. The methods were compared by using estimates of noise in velocity measurements based on the difference between the experimental map and a smooth fitted map. For the same acquisition time, FEVI with four encoding steps was more precise in velocity measurements than phase mapping. Precision was further increased by the use of eight encoding steps, but acquisition time was doubled. PMID- 7981518 TI - MR imaging evaluation of knee collateral ligaments and related injuries: comparison of T1-weighted, T2-weighted, and fat-saturated T2-weighted sequences- correlation with clinical findings. AB - The objectives of this study were to compare the ability of T1-weighted (T1W), proton density/T2-weighted (PD/T2W), and fat saturation (FS) PD/T2W magnetic resonance (MR) sequences for depiction of the knee collateral ligaments and related injuries, and to compare MR findings with clinical findings. Ten subjects with normal knee ligaments and 64 patients with suspected collateral ligament injuries underwent coronal T1W, PD/T2W, and FS PD/T2W imaging. Abnormalities ranged from edema surrounding the collateral ligaments (grade I) to complete disruption of ligamentous fibers (grade III). FS PD/T2W images improved definition of the medial collateral ligament (MCL) and lateral collateral ligament (LCL) compared with other sequences in 78% and 81% of patients, respectively. While the apparent grade of collateral ligament injury was similar with all pulse sequences in most patients, depiction of such injury was usually most conspicuous on FS PD/T2W images (MCL, 92% of patients; LCL, 38% of patients). In no patients were clinically diagnosed collateral ligament injuries undetected or understaged with MR imaging. MR findings indicated higher-grade MCL and LCL injuries than did clinical examination in 24 and 15 patients, respectively. PMID- 7981519 TI - Reduction of partial-volume artifacts with zero-filled interpolation in three dimensional MR angiography. AB - Partial-volume artifacts reduce vessel contrast and continuity (especially in small vessels) in magnetic resonance (MR) angiography. The authors applied zero filled (band-limited) interpolation to three-dimensional (3D) MR angiograms to reduce partial-volume artifacts. They demonstrated that zero-filled interpolation can also be implemented by means of voxel shifting in real space. Voxel-shifted interpolation is much less computer memory intensive than conventional zero filled interpolation. They numerically simulated the contrast loss due to partial volume artifacts and contrast recovery obtained with zero-filled interpolation. Zero-filled interpolation in all three orthogonal directions was applied to 3D MR angiography data sets from 29 human studies. These studies were obtained with the three commonly used 3D MR angiography techniques: 3D time of flight, multislab 3D time of flight, and 3D phase contrast. A substantial improvement in vessel contrast and vessel continuity was observed in all cases. PMID- 7981520 TI - Effects of MR exposure at 1.5 T on early embryonic development of the chick. AB - The potential teratogenicity of magnetic resonance (MR) field exposure on the early development of the chick embryo was examined. Eggs at four developmental stages within the first 42 hours of incubation were exposed to a static magnetic field of 1.5 T for 6 hours and to 64-MHz radio-frequency field pulses and a switched magnetic field gradient with an amplitude of 0.6 G/cm for 4 h. When the embryos were sacrificed shortly thereafter (at approximately 53 hours of incubation), the abnormality and mortality rates of exposed and unexposed (control) embryos in each of the developmental groups did not show a consistent pattern. When embryos were sacrificed on the 6th day of incubation, exposed embryos from all developmental groups showed a trend toward higher abnormality and mortality rates than their controls. More extensive studies are needed to confirm these findings. PMID- 7981522 TI - Effects of intravoxel velocity distributions on the accuracy of the phase-mapping method in phase-contrast MR angiography. AB - The phase-mapping method of phase-contrast magnetic resonance angiography is shown to be based on an implicit assumption that the intravoxel velocity distribution is symmetric about its mean velocity. The effect of asymmetric distributions on the accuracy of quantitative average velocity measurements is determined analytically and verified experimentally. An explicit formulation is developed for the estimated average velocity in a voxel as a function of the true average velocity and the asymmetry of the distribution about the true average velocity. Worst-case distributions are determined for unidirectional and bidirectional flow, and the special case of laminar flow is also investigated. Computer simulations and phantom imaging experiments demonstrate the accuracy of the analysis. For voxels with unidirectional flow, the phase-mapping method produces accurate estimates of average velocity, while results for bidirectional flow indicate possible large errors unless the aliasing velocity is increased, which decreases the signal-to-noise ratio in the resultant velocity map image. PMID- 7981521 TI - Guidelines and recommendations for MR imaging safety and patient management. III. Questionnaire for screening patients before MR procedures. The SMRI Safety Committee. AB - The authors present the third installment of the guidelines and recommendations from the Safety Committee of the Society for Magnetic Resonance Imaging (now the Society of Magnetic Resonance) concerning various issues related to the safety and management of patients undergoing magnetic resonance (MR) procedures. This document was developed to provide standardized and consistent information for use by health practitioners involved in screening patients or other individuals for MR procedures. PMID- 7981523 TI - Ex vivo evaluation of ferromagnetism, heating, and artifacts produced by heart valve prostheses exposed to a 1.5-T MR system. AB - Ex vivo testing techniques were used to determine the ferromagnetic qualities of, presence of heating in, and artifacts produced by 13 different heart valve prostheses exposed to a 1.5-T (64-MHz) magnetic resonance (MR) system. None of the heart valve prostheses showed a measurable deflection in the 1.5-T static magnetic field. Only minimal artifacts were produced during MR imaging with a fast spoiled GRASS (gradient-recalled acquisition in the steady state) pulse sequence. The largest temperature changes measured during a "worst case" MR imaging sequence (estimated average specific absorption rate, 2.5 W/kg; estimated spatial peak specific absorption rate, 7.6 W/kg) were +0.2 degree C with the implant imaged "in air" and +0.3 degrees C with the implant imaged in normal saline. Therefore, MR procedures performed with a 1.5-T (64-MHz) MR system may be performed safely in patients with any of the 13 different heart valve prostheses evaluated in this study. PMID- 7981524 TI - [The thermonuclease test used for the rapid identification of S. aureus in blood cultures]. PMID- 7981525 TI - [Current practical aspects of the use of bacteriological and serological studies in the diagnosis of human leptospirosis]. PMID- 7981526 TI - [The etiology of atypical pneumonias in adults]. PMID- 7981527 TI - [The evolution of measles morbidity and mortality in Romania after the introduction of antimeasles vaccination]. PMID- 7981528 TI - [The level of antidiphtheria and antitetanus immunity in the population of 18 counties of southern Romania and of the city of Bucharest]. PMID- 7981529 TI - [Screening-type epidemiological assessments in industrial units of various profiles for the prevalence of increases in arterial pressure values and for the carriers of risk factors for essential arterial hypertension]. PMID- 7981530 TI - [The attitude and behavior of medical students to smoking]. PMID- 7981531 TI - [The role of the C virus in the chronicity of viral hepatitis]. PMID- 7981532 TI - [The median social cost/year of a patient with HIV/AIDS]. PMID- 7981533 TI - [The epidemiological factors which interpose in the occurrence of cases of tetanus in the area of the I.S.P.C.M. Timisoara]. PMID- 7981534 TI - [Antibodies against viral hepatitis C in groups at risk]. PMID- 7981535 TI - [Vibrio cholerae 0:139 Bengal, a new serogroup with epidemic potential (the causative agent of a future pandemic?!)]. PMID- 7981536 TI - [2 outstanding representatives of our medical culture--the husband and wife George and Alice Magheru]. PMID- 7981537 TI - The problems of surgical treatment for cardiac myxoma and associated lesions. AB - Twenty-four patients with cardiac myxomas consisting of 22 left and 2 right atrial myxomas were operated on. All myxomas were removed with an excision of the attachment walls using a cardiopulmonary bypass. Two myxomas required a partial cardiopulmonary bypass from the femoral vein to the artery prior to operation because they were on the verge of becoming stuck in the atrioventricular valves and potentially causing shock. For embolic complications of myxoma, the embolus of the external carotid artery was extirpated before undergoing cardiac surgery. In a patient with pulmonary infarction, the infarcted lung was resected simultaneously. Another patient with a cerebral infarction received a clipping of an aneurysm which later appeared in the infarcted area. For associated cardiac lesions, two patients underwent a coronary artery bypass graft and one mitral valve replacement with tricuspid annuloplasty. In the former two cases, the myxoma was removed prior to coronary artery bypass grafting because the use of retrograde coronary perfusion was considered to be sufficient to protect the heart. In the latter case, the removal of the myxoma first disclosed a significant mitral lesion which had been masked by the huge myxoma. All patients but one, who died of pneumonia, showed a good recovery. In this series, the problems of surgical treatment for cardiac myxoma and associated lesions are also discussed. PMID- 7981538 TI - Risk factors influencing the short-term results of gastroduodenal perforation. AB - The purpose of this study was to evaluate the risk factors influencing the short term results of gastroduodenal perforation to determine the optimal treatment for reducing mortality. A total of 136 patients were retrospectively reviewed and the prognostic factors were examined. Seven patients died within 30 days, with an overall mortality rate of 5.1%. Mortality was significantly worse in those aged 50 years or more, when the leukocyte count was less than 9,500/mm3, when treatment was delayed more than 12h after perforation, in cases of preoperative shock and renal failure, and when associated with liver cirrhosis or an immunocompromised state. Tolerance to the time delay was inversely proportional to age, while the deaths in patients aged 65 years or younger were related to serious concurrent diseases. Shock and renal failure occurred most often in elderly patients as a result of delayed surgery, and the leukocyte count was an age-dependent prognostic indicator. Thus, age, the time interval between perforation and treatment, serious concurrent disease, shock, and renal failure were presumed to be the most important prognostic factors. Although definitive operations were performed on low-risk patients with an acceptably low mortality, it remains to be determined whether simpler procedures should be adopted for high risk patients. PMID- 7981539 TI - The effects of dopamine infusion on the postoperative energy expenditure, metabolism, and catecholamine levels of patients after esophagectomy. AB - Although dopamine is one of the most widely used vasoactive agents, its postoperative thermogenic and metabolic effects have not been studied. In this study, the effects of low-dose dopamine, given at 5 microgram/kg/min, on resting energy expenditure (REE), metabolism, and plasma catecholamine levels were examined in eight postsurgical patients. Dopamine infusion increased REE from 1,839 +/- 171 kcal/day to 2,071 +/- 170 kcal/day, and it decreased to 1,867 +/- 141 kcal/day after cessation of the infusion. Dopamine also increased the plasma levels of glucagon from 109.4 +/- 8.7 pg/ml to 132.5 +/- 8.0 pg/ml, and it decreased to 102.9 +/- 11.1 pg/ml after cessation of the infusion. The plasma levels of dopamine before, during, and after the infusion were 116.1 +/- 18.3, 161.1 +/- 25.6 and 121.4 +/- 17.2 ng/ml, respectively. Insulin and glucose were affected by dopamine, but changes in their plasma levels did not parallel the dopamine levels. Epinephrine and norepinephrine were increased by the infusion of dopamine and continued to increase even after its cessation. The results of this study revealed that low-dose dopamine increased REE in postsurgical patients and that this might be associated with the concomitant increase in plasma glucagon. PMID- 7981540 TI - OK432 inhibits experimental hepatic metastasis of colon adenocarcinoma ACL-15 in F344 rats. AB - The effect of OK432 on hepatic metastasis, induced by inoculating 1 x 10(6) ACL 15 cells from a rat colon adenocarcinoma cell line into the ileocolic vein of male F344 rats, was investigated in this study. Metastases were detected 14 days after inoculation in the control rats, however, pretreatment 3 days prior to the tumor cell inoculation with an anti-asialoGM1 antibody, which eliminates natural killer (NK) cell activity in vitro, increased the number of hepatic metastases, shortened the survival time, and decreased the NK activity of the nonparenchymal liver cells (NPC). In contrast, pretreatment with OK432 2 days prior to tumor inoculation significantly decreased the number of hepatic metastases, prolonged the survival time, and augmented the NK activity of the NPC, although treatment with OK432 3 or 7 days after inoculation did not decrease the number of hepatic metastases. Moreover, NPC from the OK432-pretreated rats had a marked antitumor effect against ACL-15 cells in the Winn's neutralization test. The results of this study indicate that pretreatment with OK432 before tumor cell inoculation inhibits hepatic metastasis in this experimental model, possibly by augmentating liver-associated NK activity. PMID- 7981541 TI - The effects of feeding and secretin administration on the pancreaticoduodenal papilla of conscious dogs. AB - The aim of this study was to define the functional role of the pancreaticoduodenal papilla (PDP) in the regulation of pancreatic outflow into the duodenum in response to feeding and secretin administration in conscious dogs. The canine model we developed allowed for measurement of the pancreatic ductal pressure and pancreatic outflow simultaneously in a physiological state without interfering with the flow of pancreatic juice via the intact sphincter of the duodenal papilla. Feeding increased the pancreatic outflow from 2.8 +/- 0.2 to 13.4 +/- 1.3 ml/15 min with a slight increase in the pancreatic ductal pressure from 8.5 +/- 0.6 to 13.7 +/- 1.4 cmH2O. The administration of secretin increased the pancreatic outflow from 2.8 +/- 0.2 to 12.7 +/- 1.0 ml/15 min without increasing the pancreatic ductal pressure. The viscosity of the pancreatic juice increased during exposure to food, but decreased following food intake and secretin administration, after which the PDP seemed to dilate by about 40% of the fasting value. The results suggest that PDP changes its opening to maintain the pancreatic ductal pressure below a certain level, even if pancreatic secretion into the pancreatic duct increases due to food intake and secretin administration. PMID- 7981542 TI - An in vitro evaluation of prostaglandin E1 and I2 on hypothermic injury to immature myocytes. AB - The purpose of this study was to evaluate the functional and biochemical effects of Prostaglandin E1 (PGE1) and prostaglandin I2 (PGI2) on cardiac myocytes incubated under hypothermic conditions. Cardiac myocytes were isolated from neonatal rat ventricles and cultured for 4 days with MCDB 107 medium. Following this, 12.5 x 10(5) myocytes/flask were incubated at 4 degrees C for 24 h in media with PGE1, at concentrations of 0 M (group E0), 10(-9) M (group E1), 10(-8) M (group E2), 10(-7) M (group E3), or 10(-6) M (group E4); or with PGI2 at concentrations of 0 M PGI (group I0), 10(-9) M (group I1), 10(-8) M (group 12), 10(-7) M (group I3), or 10(-6) M (group I4). After hypothermic incubation, creatine phosphokinase (CPK) and lactate dehydrogenase (LDH) were measured, and the myocytes were then cultured for 24 h at 37 degrees C to evaluate the recovery of the myocyte beating rate. Of the PGI2 groups, only group I2 recovered significantly more than the control group (group I0), at 47.9 +/- 28.5% (mean +/- SD) of the control, being the beating rate prior to hypothermic incubation, whereas it was 18.1 +/- 9.7% in group I0 (P < 0.025); however, there were no significant differences among the PGE1 groups. Moreover, the release of CPK and LDH was significantly suppressed in group 12 compared to the control, being 57.7 +/- 27.6 mIU/flask (P < 0.05) and 275.1 +/- 83.0 mIU/flask (P < 0.025), respectively, in group I2, and 96.8 +/- 38.3 mIU/flask and 439.6 +/- 147.1 mIU/flask in group I0. Again, no significant differences were observed among the PGE1 groups. In conclusion, PGI2 was found to have a direct cytoprotective effect on immature myocytes which suggests that PGI2 may promote cardiac preservation in the neonatal period. PMID- 7981543 TI - Serum hyaluronic acid for the assessment of graft viability in porcine liver transplantation. AB - For the assessment of graft viability, serum hyaluronic acid (HA) levels during porcine orthotopic liver transplantation were measured in two groups: group 1 (viable: n = 5) in which allografts were transplanted following a minimal cold (4 degrees C) preservation, and group 2 (nonviable: n = 4) in which allografts were transplanted after cold static storage (4 degrees C) for 24 h in University of Wisconsin solution. The changes in the HA levels reached a significant difference between the two groups at 30 min after reperfusion (P < 0.02). In group 1, all animals survived for over 4 days, while all animals in group 2 died within 24 h. The serum HA also demonstrated a significant correlation with prothrombin time, beta-glucuronidase, and aspartate aminotransferase at 120 min after reperfusion. These results suggest that the measurement of serum HA is a potentially effective index for evaluating hepatic allograft viability. PMID- 7981544 TI - Stimulatory effect of EGF and inhibitory effect of sialoadenectomy on growth of an EGF receptor-hyperproducing human gastric cancer xenograft in nude mice. AB - We recently established epidermal growth factor (EGF) receptor-hyperproducing human gastric cancer xenografts in nude mice. The present study was designed to examine whether the growth of a xenograft having 1,098 +/- 276 fmol/mg protein of EGF receptor would either be stimulated by the administration of EGF or inhibited by the removal of the submandibular glands (sialoadenectomy) which contain a large amount of EGF. A miniosmotic pump containing 2 micrograms or 20 micrograms of EGF was implanted on the back of the animals in the EGF stimulation experiments. The tumor growth was stimulated by the administration of EGF (P < 0.01), and the doubling time of the tumor was reduced relative to the controls (P < 0.01). Both the mitotic indices and the bromodeoxyuridine (BrdU)-labeling indices of the tumor were higher than those of the controls (P < 0.01). Tumor growth inhibited by the sialoadenectomy (P < 0.05) while the tumor doubling time was prolonged compared with the sham-operated mice (P < 0.05). These results suggest that the growth of a human gastric cancer xenograft may be modulated by EGF. PMID- 7981545 TI - Banding a hemodialysis arteriovenous fistula to decrease blood flow and resolve high output cardiac failure: report of a case. AB - We report herein the successful surgical treatment of a patient with high-output cardiac failure which developed from a high-flow hemodialysis arteriovenous fistula of the Brescia-Cimino type. Banding correction of the venous limb of the fistula with a woven Dacron prosthesis resulted in marked improvement of the cardiac failure. An ultrasonic study showed the fistula flow of 3.2 l/min to be as high as 40% of the resting cardiac output, or 8.0 l/min, before banding, while an intraoperative electromagnetic study was useful for controlling the degree of banding and showing the decrease of fistula flow from 3.7 l/min to 1.4 l/min. PMID- 7981546 TI - Bilateral malignant lymphoma of the breast in patients with a familial history of cancer: a report of three cases. AB - We report three cases of bilateral malignant lymphoma of the breast in patients with a familial history of cancers. All the patients had B-cell malignant lymphoma and were treated by a radical mastectomy and polychemotherapy. Bilateral tumors were detected synchronously in one case, whereas the second tumors in the other cases occurred 4 years and 8 years after the initial treatment. Although the patients had no relevant past history, these cases were notable for the fact that all were associated with a familial history of cancers. One patient had a definite familial history of breast cancer, that is to say, her mother, sister and brother all suffered from this disease. The brother of another patient died of gastric cancer while two of her uncles each suffered from sarcoma of the lower extremities and a brain tumor, respectively. As for the remaining patient, one of her maternal uncles and an aunt also died of prostate cancer and leukemia, respectively. However, only one out of seven patients with unilateral malignant lymphoma of the breast used for comparison had a familial history of cancer. A possible relationship between bilateral primary malignant lymphoma of the breast and a familial history of cancer is suggested. PMID- 7981547 TI - Surgical excision of a broad-based left atrial myxoma: report of a case. AB - We report herein the case of a 72-year-old woman who underwent successful resection of an unusual type of broad-based left atrial myxoma. The tumor, which was attached to the fossa ovalis and anterior wall of the left atrium posterior to the aorta, was resected en bloc with the interatrial septum and the affected free wall of the left atrium. The defect in the left atrium and atrial septum was then reconstructed with an equine pericardial patch. To our knowledge, this type of cardiac myxoma, with a base extending from the septum to the atrial wall, has not been previously reported. PMID- 7981548 TI - Primary malignant fibrous histiocytoma of the diaphragm: report of a case. AB - We present herein the case of a 55-year-old man with primary malignant fibrous histiocytoma (MFH) of the diaphragm. He was admitted to our hospital with right anterior chest pain, where diagnostic imaging showed a huge tumor in the right diaphragm with a tumor thrombus in the vena cava, spreading to the left lobe of the liver and the pericardium. Although invasion into the right lung was identified at the time of surgery, the entire tumor was removed. Histopathological examination of the resected specimen revealed the characteristics of MFH. We discuss the clinical features of this patient in comparison with the few previous reports on MFH of the diaphragm. PMID- 7981549 TI - Mitral valve replacement after atrioventricular canal repair in adults: report of three cases. AB - Three cases of adults who required a mitral valve replacement (MVR) following repair of an atrioventricular (AV) canal are presented herein. In adult patients with an AV canal, the deformity of the mitral valve is sometimes too advanced for adequate repair, and therefore, residual mitral regurgitation frequently causes intractable cardiac failure despite appropriate medical management. Thus, for adults with an AV canal associated with severe valvular deformities, MVR should be considered from the initial operation to obtain a significantly better outcome. PMID- 7981550 TI - Splenic arterial hemorrhage in pancreatitis: report of three cases. AB - Gastrointestinal hemorrhage is a rare complication of pancreatitis and can involve any of the peripancreatic vessels. The three cases reported herein illustrate the involvement of the splenic artery in diverse forms of pancreatitis: chronic pancreatitis, a pancreatic pseudocyst, and necrotizing pancreatitis. Bleeding was controlled in all cases by a bipolar ligation of the bleeding vessel at surgery. PMID- 7981551 TI - Gastric carcinoma resected 95 months after being diagnosed: report of a case. AB - It is usually assumed that patients with gastric carcinoma will almost certainly die within 5 years if they do not receive treatment. We report herein a rare case of curative gastrectomy being performed 95 months after gastric carcinoma was diagnosed. A 37-year-old Japanese man had an upper gastrointestinal endoscopy with biopsy which revealed moderately differentiated adenocarcinoma of the stomach. This was diagnosed as type IIc early gastric carcinoma with ulceration but he refused surgery. At 45 years of age, 95 months later, he presented to our hospital with melena, at which time lesions in an identical location had enlarged to Borrmann type 3 advanced gastric carcinoma. Thus, a total gastrectomy with regional lymph node dissection was performed. Although there was no liver or peritoneal metastasis, the regional lymph nodes were involved; however, the patient recovered well and is still alive without any further recurrence roughly 4 years postoperatively. The natural history of gastric carcinoma and the malignant cycle are discussed following the presentation of this case. PMID- 7981552 TI - The presence of tumor necrosis factor-alpha and its antibody in the sera of cachexic patients with gastrointestinal cancer. AB - Although cancer cachexia has been shown to involve several cytokines, the tumor necrosis factor-alpha (TNF) has rarely been detected in such patients. In this study, sera from 21 patients with cancer cachexia were examined for the presence of TNF and the anti-TNF antibody using an enzyme-linked immunosorbent assay (ELISA) and Western blotting, respectively. All of the patients had recurrent cancer and manifested the characteristics of progressive body weight loss. TNF was found in the sera of four patients (20%) at levels ranging from 10.4 to 53.1 pg/ml, while a positive reaction for the anti-TNF antibody was detected in the sera from six patients (30%), two of whom showed both TNF and its antibody. Thus, either TNF or the anti-TNF antibody was present in the sera from 8 of 21 patients (40%). The results of this study indicate that TNF may be present in the circulation of at least 40% of cachexic patients, and suggest that it may be one of the main mediators of cancer-associated cachexia. PMID- 7981553 TI - Eosinophilia in newborn infants. AB - To evaluate the clinical significance of eosinophilia in newborn infants, 261 admissions to the neonatal unit over a 12-month period were studied retrospectively; 33 babies with eosinophilia (> 1.0 x 10(9)/l) were studied. Clinical and laboratory data for the first month of life were compared, where available, between gestational age-matched pairs with and without eosinophilia. Of the 33 babies with eosinophilia, 23 were > 26 weeks' gestation and all had age matched controls; 10 were < or = 26 weeks' gestation but had no appropriate gestational age-matched controls. Babies > 26 weeks' gestation with eosinophilia had a significantly higher number of septic episodes than controls: 20 of 23 versus 4 of 23. All 10 babies < or = 26 weeks' gestation with eosinophilia developed sepsis. Infections with gram-negative organisms and necrotizing enterocolitis occurred only in babies who developed eosinophilia. In 5 babies no cause for the eosinophilia was found. In conclusion, eosinophilia in the newborn is usually explainable and is most often associated with infection. PMID- 7981554 TI - Respiratory water loss and oxygen consumption in full-term infants exposed to cold air on the first day after birth. AB - Respiratory water loss, oxygen consumption, carbon dioxide production and skin blood flow were measured continuously in nine full-term infants on the first day after birth. After at least 18 min of measurements with the infant asleep in an incubator, with an air temperature of 33 degrees C and a relative humidity of 50%, the temperature of the incubator air was lowered to less than 27.5 degrees C. This resulted in a significant decrease in skin temperature and peripheral skin blood flow, while the infant's core temperature remained unchanged. At the same time, mean respiratory water loss increased from 3.7 to 6.1 mg/kg.min, which can be explained partially by the decrease in ambient humidity that accompanied the decrease in air temperature. In addition, mean oxygen consumption increased from 5.3 to 7.9 ml/kg.min and mean carbon dioxide production increased from 3.8 to 5.9 ml/kg.min. There was no concomitant increase in motor activity. Thus, when the newborn infants were exposed to cool air, they reacted with an increase in respiratory water loss, oxygen consumption and carbon dioxide production before their core temperature was affected and without increasing their motor activity. PMID- 7981555 TI - Reactive hyperemia of skin microcirculation in septic neonates. AB - Reactive hyperemia after 1 min of arterial occlusion was studied in back, thigh and heel skin of 40 preterm and full-term neonates using laser Doppler flowmetry. Twelve infants had clinical signs of septicemia, but normal laboratory tests at the time of fluxmetry. However, CRP, leukocyte count and the ratio of immature to total neutrophils increased during the following days and septicemia was confirmed by positive blood cultures (septic group). Seven neonates with clinical signs of septicemia had developed neither positive blood cultures nor laboratory signs (non-septic group). Fifteen were healthy neonates. In the septic neonates, time to reach maximal hyperemia, maximum post-occlusive hyperemia and recovery time of skin perfusion were increased significantly in back and thigh skin and the heal skin temperature was decreased when compared to healthy neonates. Healthy and non-septic neonates showed no significant difference in any of the parameters. We conclude that altered reactive hyperemia in the skin may be an earlier sign of neonatal septicemia than laboratory tests. PMID- 7981556 TI - A persisting secular trend for body measurements in Dutch children. The Oosterwolde II Study. AB - To investigate whether the secular trend for growth in Dutch children still exists, the Oosterwolde I study of 1980 was repeated in 1989. A persisting secular trend was visible for height while the z scores of body proportions show no change during the past 10 years, which suggests that there is no change in the timing of puberty. PMID- 7981557 TI - Travel and changes in routine do not increase the risk of sudden infant death syndrome. AB - We investigated the relationship between travel and changes in routine and the sudden infant death syndrome (SIDS) among 485 SIDS cases compared with 1800 randomly selected control infants. There was no increased risk of SIDS with travel. Special events, such as christenings, were not associated with an increased risk of SIDS. However, visits to and by friends or relatives were associated with a significantly reduced risk of SIDS after controlling for potential confounders (odds ratios = 0.70; 95% confidence interval = 0.52, 0.96). These findings may indicate less social support in SIDS cases. PMID- 7981558 TI - Hydrolyzed lactalbumin-based oral rehydration solution for acute diarrhoea in infants. AB - The addition of different organic substrates to standard glucose oral rehydration solution (G-ORS) has been shown to improve the intestinal absorption of sodium and water, and thereby decrease stool losses. Therefore, we evaluated, in infants with acute diarrhoea, the safety and efficacy of three oral rehydration solutions (ORS) which had the same concentrations of electrolytes (with sodium 60 mmol/l) but different substrates of proteins and carbohydrates. One solution (LAD-ORS) contained hydrolyzed lactalbumin (LAD) with maltodextrin and sucrose, a second (MS-ORS) was identical but without LAD and a third (G-ORS) was standard glucose ORS. The three solutions were compared in a double-blind, randomized trial in 74 hospitalized well-nourished children in Panama and the United States. All three oral rehydration solutions were equally efficacious and safe in these children, 54% of whom were infected with rotavirus. There was no suggestion that hydrolyzed lactalbumin or maltodextrin provided any advantage over glucose-ORS in terms of stool output or in duration of diarrhoea. We conclude that all three solutions are efficacious in the therapy of acute diarrhoea in infants. PMID- 7981559 TI - Evaluation of a maize-cowpea-palm oil diet for the dietary management of Nigerian children with acute, watery diarrhea. AB - A randomized clinical trial was carried out to compare a locally available maize cowpea-palm oil diet (group MCP) with a commercially produced lactose-free, soy protein isolate formula (group SF) for the dietary management of 69 Nigerian boys, 6-24 months of age, hospitalized for acute, watery diarrhea. Although the treatment groups were generally similar initially, the children in group SF had slightly lower mean weight-for-age z scores (p = 0.08), lower serum bicarbonate levels (p = 0.04) and greater stool outputs during the period of rehydration before the diets were initiated (p = 0.01). Rates of treatment failure in group MCP (5.7%) and group SF (8.8%) were similar (p = 0.67). There were no significant differences in the adjusted mean stool outputs by study group on days 1-5, but the children in group SF had slightly lower fecal weights on day 6 (p = 0.05). Children in group MCP had a substantially reduced duration of liquid stool excretion (estimated median duration 42 h versus 140 h; p < 0.001). On the other hand, children in group SF consumed considerably more of their diet, had greater net absorption of macronutrients and greater rates of weight gain than those in group MCP. We conclude that children can safely consume the MCP diet during acute, watery diarrhea without increasing their risk of treatment failure or augmenting stool output. However, the diet may not be adequate as a sole source of nutrients beyond the period of acute illness. PMID- 7981560 TI - Zinc supplementation increases growth velocity of male children and adolescents with short stature. AB - We assessed the effect of zinc supplementation on growth velocity in 79 children and adolescents (48 males, 38 females) with idiopathic short stature. Their height-for-age was < 5th percentile (NCHS standards) and their weight-for-age was normal. Patients were assigned randomly to a supplemented group (S) to receive Zn 10 mg/day or to a placebo (P) group, according to gender and age, and were followed-up for 12 months using a double-blind design. Weight, height, armspan, length of lower segment and plasma and hair concentrations of Zn were measured at 0, 3, 6 and 12 months. On admission and at 6 months, energy, protein, dietary fiber and zinc intakes were similar for groups S and P; mean zinc intake was < 6.5 mg/day. No differences were found in plasma zinc, hair zinc, weight, armspan or lower segment increments. Pre-adolescent males in group S had a significantly greater increase in stature compared with group P (6.2 +/- 2.1 versus 4.5 +/- 1.2 cm/year p < 0.025); z score improved from -2.42 to -2.24 in group S and from 2.63 to -2.61 in group P. For adolescent males, the difference was also significant (8.3 +/- 1.5 versus 6.2 +/- 2.1 cm/year; p < 0.025). No differences were noted in females. In Chilean male schoolchildren and adolescents with idiopathic short stature, zinc supplementation increases growth velocity over a 12-month period. PMID- 7981561 TI - Age and gender specific serum lipid and apolipoprotein fractiles of Finnish children and young adults. The Cardiovascular Risk in Young Finns Study. AB - We present fractile data on serum lipids and apolipoproteins A-l and B for children and young adults from the cardiovascular risk in young Finns study cohort of 1986. The sample comprised 2370 fasting children and young adults (1114 males and 1256 females) aged 9, 12, 15, 18, 21 and 24 years. The determinations were performed in duplicate with standard methods. LDL-cholesterol values were calculated. The limits for clearly pathological values (exceeding the 97.5th percentile) irrespective of age and gender were 7.5 mmol/l, 5.0 mmol/l, 3.5 mmol/l and 1.4 g/l for serum total cholesterol, LDL-cholesterol, triglycerides and apolipoprotein B, respectively. Corresponding values (below the 2.5th percentile) for HDL-cholesterol, apolipoprotein A-l, HDL2- and HDL3-cholesterol were 0.80 mmol/l, 1.0 mg/l, 0.20 mmol/l and 0.70 mmol/l, respectively. Approximately 79%, 33% and 7% of males had serum total cholesterol values greater than 4.0 mmol, 5.0 mmol/l and 6.0 mmol/l, respectively. Corresponding percentages for females were 87%, 43% and 10%. However, age-related differences were marked. The prevalence of values, e.g. greater than 6 mmol/l according to age, ranged from 6 to 13% in females and from 3 to 12% in males, emphasizing the need for age specific reference values. Additionally, postpubertal values for total and LDL cholesterol tended to be slightly lower compared to prepubertal values, indicating that the reference values for adults do not apply to adolescents and young adults. The age-related changes in lipid levels were evident in each fractile and were especially accentuated in higher fractiles. Fluctuations with age were more pronounced in males than in females. These results are intended to be applied as reference values for diagnosing dyslipidemias. PMID- 7981562 TI - Diabetes mellitus in cystic fibrosis: effect of insulin therapy on lung function and infections. AB - The effect of insulin therapy on lung function and lung infections was studied in a retrospective case-control design in 18 diabetic cystic fibrosis (CF) patients; 18 non-diabetic CF patients, matched for sex, age and presence of chronic Pseudomonas aeruginosa lung infection, served as controls. Parameters of CF clinical status were collected for six years before and two years after the onset of insulin therapy in the diabetic patients. Before onset of insulin therapy, body mass index (BMI) and forced vital capacity (FVC) in (pre)diabetic patients deviated increasingly from those in control patients. Decreases in BMI and lung function during the past three months before onset of insulin therapy were reverted within three months of insulin therapy. From three months to two years after onset of insulin therapy, differences in BMI and lung function diminished between diabetic and control patients. After two years of insulin therapy, BMI was similar in diabetic and non-diabetic patients and the percentage differences in forced expiratory volume in 1s (FEV1) and FVC between the two groups were similar to those found six years before the onset of insulin therapy. The finding that insulin therapy improves lung function in diabetic CF patients suggests strongly that the insidious decline in lung function seen during the years before the diagnosis of diabetes mellitus results from the pre-diabetic condition. After onset of insulin therapy, the percentages of sputum examinations positive for Haemophilus influenzae and Streptococcus pneumoniae decreased in the diabetic patients, whereas parameters of lung infections with P. aeruginosa and Staphylococcus aureus remained unchanged.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7981563 TI - Prognosis of asthma in children: a cohort study into adulthood. AB - Fifty-six children with asthma, randomly selected from a hospital clinic, were followed prospectively for 15 years from a median age of 9-24 years of age. Four follow-ups were performed and included scoring of the frequency of wheezing, the need for medication, admissions to hospital, spirometry, skin prick tests and RAST to common inhaled allergens, and evaluation of living conditions. One patient died of asthma. The remaining 55 reported for all follow-ups. After the second follow-up at a median age of 13 years, all parameters of severity of asthma showed improvement, which was significant at the last follow-up when all subjects were more than 20 years of age. Only 16% of the subjects had been free from wheezing and medication the year prior to the last follow-up. Approximately 90% of the children had clinical allergies and positive allergy tests to pollens and danders and the majority of children retained both the allergies and the reactivity into adulthood. Reactivity to moulds and mites was less frequent (40% and 31%, respectively) and seemed to decrease in adulthood. Approximately 10% of the subjects developed neither clinical allergies nor reactivity in allergy tests. Children with atopic eczema usually retained their eczema as adults. Frequent wheezing and abnormal spirometry in childhood and early onset of asthma were associated with poorer outcome. The social prognosis was excellent. PMID- 7981564 TI - Acute rheumatic fever in children in the Ankara area in 1990-1992 and comparison with a previous study in 1980-1989. AB - Two hundred and twenty-eight patients with acute rheumatic fever (ARF), who were admitted to Dr Sami Ulus Children's Hospital between January 1990 and November 1992, were evaluated. Compared with the 1980s, an increase in the frequency of the disease was observed. The majority of patients (56.5%) were between 9 and 12 years old and 36.8% were admitted in winter. One hundred patients had arthritis only, 59 carditis and 40 chorea; 5 had carditis and chorea and 24 had arthritis and carditis. Nineteen percent of patients had a history of a previous attack. Seven of 84 patients with carditis had congestive heart failure and 2 had pericarditis. Cardiomegaly was present in 36 patients. The mitral valve was affected in 77 patients, tricuspid valve in 1 patient and both miral and aortic valves in 6 patients. One patient died as a result of severe congestive cardiac failure. Twenty-one patients had a recurrent attack. We observed that ARF is still a significant cause of morbidity in our country. As the disease is preventable by the eradication of streptococcus, we conclude that more effort should be made in the early detection and treatment of streptococcal infections. PMID- 7981565 TI - Reliability of subjective estimates of exercise capacity after total repair of tetralogy of Fallot. AB - Sixty-nine patients (age 10 +/- 3.5 years, median 9.7 years) operated on for tetralogy of Fallot, underwent exercise testing 5.1 +/- 2.5 years after total correction. Aerobic capacity was assessed by the ventilatory threshold method. After the exercise test, parents completed a validated standardized questionnaire to evaluate the habitual level of physical activity of their child. They were then asked to place their child into one of three groups, describing their child's activity level, compared to normals (below average, average and above average). In the average and above-average groups, 73% and 65% of the patients were misclassified when compared to objective exercise testing. However, in the below-average group, no misclassifications were found. Subjective estimates of activity level, and consequently exercise tolerance, were poorly associated with objective measurements of exercise performance in these patient groups. Our results question the reliability of self-reported estimates of physical activity level and consequently exercise capacity in children after surgical correction of tetralogy of Fallot. PMID- 7981566 TI - Detection of immunoglobulin (IgG and IgA) anti-outer-membrane proteins of enteropathogenic Escherichia coli (EPEC) in saliva, colostrum, breast milk, serum, cord blood and amniotic fluid. Study of inhibition of localized adherence of EPEC to HeLa cells. PMID- 7981567 TI - Clinical implications of basic research in the neurobiology of infant-parent interaction in the newborn period. PMID- 7981568 TI - Prostaglandin E1 in a case of cardiogenic shock in a very low-birth-weight infant. PMID- 7981569 TI - Paediatrics and child psychiatry: past, present and future. AB - The historical development of the relationship between paediatrics and child psychiatry is outlined and the closer working relationships between the two disciplines over the past 30 years are noted. Various ways in which child psychiatrists can contribute to paediatric practice are described, as well as the degree to which paediatricians can contribute to an understanding of child psychiatric disorders. It is suggested that new developments in paediatric practice and an increase in interest in genetic and brain mechanisms in child psychiatric disorders, will increase the need for collaboration between the two specialties. PMID- 7981570 TI - Collaboration between child psychiatry and paediatrics: the state of the relationship in Norway. AB - In Norway, the first paediatric department was founded in Oslo 100 years ago. The first child psychiatric department was opened in 1950. To assess qualitative and quantitative aspects of child psychiatric liaison work, questionnaires were sent to the heads of 25 paediatric departments and 53 child psychiatric units. Scarce child psychiatric resources were spent in paediatrics. The average score for satisfaction with collaboration was moderate (5.5 on a 10-cm visual analogue scale) and agreement between the parties was modest. Improvement will involve development of a common language and a shared model for understanding the psychosocial aspects of acute and chronic childhood illnesses. In-service training for paediatricians in child psychiatry and vice versa may help. Both parties indicated a need for more training in consultation/liaison and in multi professional assessments and therapeutic interventions with children with physical illnesses. PMID- 7981571 TI - Cholestatic pruritus: effect of phototherapy on pruritus and excretion of bile acids in urine. AB - Pruritus associated with hepatic cholestasis may cause significant morbidity and its correlation to retention of bile acids in skin is inconsistent. Available treatment modalities are only partially effective and can have several adverse effects. Phototherapy has recently been reported to improve cholestatic pruritus, but has not been evaluated previously in children, and its mechanism is still unclear. We report the outcome of multiple Daylite phototherapy treatments over two years in a seven-year-old child with chronic hepatic cholestasis that was resistant to other therapeutic modalities. Bile acid levels in urine were used as markers of effectiveness in parallel with clinical response. Night phototherapy alone increased the bile acids/creatinine ratio in urine from 1.54 +/- 0.04 mumol/mg at baseline to 2.07 +/- 0.29 mumol/mg. Continuous phototherapy combined with night diuresis raised the ratio further to 2.28 +/- 0.55 mumol/mg. Night diuresis alone had no effect. Continuous phototherapy combined with night diuresis raised the bile acids/creatinine ratio by 44% on the first day and by 61% on the second day, but declined to baseline on the third day of treatment. A marked clinical improvement was noted for one week following two days of phototherapy. This schedule has been repeatedly effective in improving pruritus for approximately one year and may be due to the ability of phototherapy to enhance excretion of bile acids and other possible pruritogens into urine. PMID- 7981572 TI - Carbohydrate-deficient glycoprotein syndrome with previously unreported features. AB - A boy with carbohydrate-deficient glycoprotein syndrome died at five months of age in status epilepticus. Postmortem examination failed to show the classically observed olivopontocerebellar atrophy. Two previously unreported features were present: cataracts from the first week of life and lysosomal storage affecting mainly the anterior horn neurons of the spinal cord. PMID- 7981573 TI - Steroid biosynthesis inhibitors in Cushing's syndrome. PMID- 7981574 TI - Secretion of growth hormone and thyroid-stimulating hormone in patients with dementia. AB - We studied the growth hormone (GH) response to GH-releasing hormone (GHRH) and the thyroid-stimulating hormone (TSH) response to thyrotropin-releasing hormone (TRH) in four groups of patients with dementia and examined whether GH and TSH secretion is altered in patients with Alzheimer's disease. The four groups included those with Alzheimer's disease (n = 28), parkinsonism with dementia (n = 10), progressive supranuclear palsy with dementia (n = 10), and dementia of vascular origin (n = 28). The results showed no differences among the four groups in GH response to GHRH (12.2 +/- 2, 10.7 +/- 2, 8.9 +/- 1.1, and 9.9 +/- 1.9 micrograms/ml, respectively); there was no correlation between GH response to GHRH and sex, stage of the disease, or cerebral atrophy. The proportion of patients with exaggerated, normal, or lower GH response was similar in the four groups in terms of TSH response to TRH (9.2 +/- 0.9, 11.1 +/- 1, 11.1 +/- 1, and 10.3 +/- 1 mU/ml, respectively), nor was there a correlation between TSH response to TRH and sex, stage of the disease, cerebral atrophy, or GH response to GHRH. The proportion of those with exaggerated, normal, or lower TSH response was similar in the four groups. Cerebrospinal somatostatin levels were similar in Alzheimer's disease and vascular dementia patients. These findings indicate that neither GH response to GHRH nor TSH response to TRH provides a useful diagnostic adjunct in Alzheimer's disease patients. PMID- 7981575 TI - Low interleukin-2 receptor levels in serum of patients with insulin-dependent diabetes. AB - Interleukin-2 receptors are released in the circulation in response to antigenic ro mitogenic stimulation of T-lymphocytes. Abnormal serum interleukin-2 receptor levels have been found in young children with type 1 diabetes and "prediabetes." We measured interleukin-2 receptor levels in 17 patients with newly diagnosed type 1 diabetes, 21 patients with long-standing type 1 diabetes, 19 patients with long-standing type 2 diabetes, 19 islet-cell antibody positive nondiabetic polyendocrine patients, 12 islet-cell antibody-positive first-degree relatives of patients with type 1 diabetes and compared the results to age- and sex-matched normal controls. We found significantly lower interleukin-2 receptor levels in patients with newly diagnosed and long-standing type 1 diabetes compared to normal controls (87 +/- 11 and 93 +/- 11 vs. 142 +/- 25 and 132 +/- 40 U/ml, P < 0.001 and P < 0.01). There were no significant differences in interleukin-2 receptor levels between prediabetic groups and normal controls or patients with long-standing type 1 or type 2 diabetes. There was no correlation between glycosylated hemoglobin, blood glucose levels, and interleukin-2 receptor in the groups with long-standing type 1 or type 2 diabetes. We conclude that patients with type 1 diabetes have low interleukin-2 receptor serum levels. This phenomenon is acquired close to disease onset and is unlikely to be an early markers of type 1 diabetes. PMID- 7981576 TI - Contrast-enhanced computed tomography for demonstration of bilateral renal cortical necrosis. AB - Bilateral renal cortical necrosis as a rare form of acute renal failure was encountered in two patients with sepsis and acute renal failure. In both cases contrast-enhanced computed tomography showed characteristic findings: absent specification of the renal cortex and enhancement of subcapsular and juxtamedullary areas and of the medulla without excretion of contrast medium. Establishing an early diagnosis and visualizing the extent of renal cortical necrosis by means of contrast-enhanced computed tomography allow a prognostic evaluation of renal function and further planning of therapy. PMID- 7981577 TI - Impact of hormone replacement therapy on postprandial lipoproteins and lipoprotein(a) in normolipidemic postmenopausal women. AB - In 43 normolipidemic postmenopausal women we studied fasting and postprandial (oral fat load with 50 g fat per square meter; blood sampling for 5 h) lipoprotein components and lipoprotein(a) levels before and with the administration of conjugated equine estrogens opposed by medrogestone (on days 11 21). Data was compared intraindividually; the second testing was performed during the last 5 days of the combined estrogen/progestogen phase of the third cycle. Fasting low-density lipoprotein (LDL) and total cholesterol concentrations decreased significantly; high-density lipoprotein (HDL) cholesterol, including subfractions HDL2 and HDL3, was not changed. Fasting triglyceride concentrations increased. All lipoprotein fractions measured showed a postprandial elevation with the exception of chylomicron cholesterol concentrations. There was a significant effect of hormone replacement therapy on the postprandial course of total cholesterol (decrease; P < 0.001), VLDL cholesterol (increase; P = 0.025), and the triglyceride proportion in the LDL plus HDL fraction (increase; P < 0.001). With hormone replacement therapy the postprandial curve of total triglycerides was increased only 1 h after the fat load while chylomicron triglyceride concentrations were lowered after 5 h. VLDL triglycerides were not influenced. In all patients with lipoprotein(a) levels above 10 mg/dl, this parameter decreased (about 25%). Although increasing fasting triglyceride concentrations, hormone replacement therapy does not bring about an exaggerated postprandial increase in triglycerides. Postprandial chylomicron clearance is evidently promoted. Hormone replacement therapy leads to a small increase in triglycerides in the LDL plus HDL fraction by inhibiting hepatic lipase activity. Moreover, the decrease in lipoprotein(a) levels may contribute to the antiatherosclerotic effect. PMID- 7981579 TI - The influence of nicotine on performance, mood, and physiological parameters as related to smoking habit, gender, and suggestibility. AB - Based on previous observations that sensory suggestibility might be related to cholinergic drug effects, and that individual susceptibility to nicotine as defined by response differences to various doses is lower in males, nonsmokers, and highly suggestible subjects, the present study investigated whether nicotine serum blood levels, cardiovascular responses, and sensory suggestibility show differences according to gender and smoking habit, and whether differences in nicotine susceptibility measured by a discrimination task by subjective ratings on activation can be reproduced in the direction predicted by the previous data. In a double-blind threefold cross-over design 48 subjects divided according to smoking habit, gender, and sensory suggestibility were tested in balanced order under the influence of an oral dose of 0, 0.014, or 0.028 mg/kg body weight of nicotine. Results revealed higher serum levels of nicotine in males and smokers, a dose-dependent increase in heart rate and systolic and diastolic blood pressure, partly interacting with gender or smoking habit (females and nonsmokers showing larger increase with the low doses), and a change in suggestibility in the expected direction (decrease with the low dose, increase with the large one only in female nonsmokers). A fourfold interaction among dose, smoking habit, gender, and suggestibility for the discrimination task partly reproduced the observations of higher nicotine susceptibility in females and non-smokers, whereas suggestibility did not seem to reveal the expected changes. Also, on a subjective level larger doses were necessary to make male smokers feel activated, while the other groups showed the biphasic response pattern to the two nicotine doses. In conclusion, the data justify further research on the concept of nicotine susceptibility defined by biphasic effects of nicotine on vigilance. PMID- 7981578 TI - Study on growth hormone and insulin secretion in myotonic dystrophy. AB - Growth hormone (GH) levels were measured in 12 patients with myotonic dystrophy (MD; 7 men and 5 women, aged 21-49 years) and 14 volunteers after administration of 100 micrograms GH-releasing hormone (GHRH; 1-29). A 75-g oral glucose tolerance test was carried out to determine glucose, insulin, plasma C-peptide, and urinary C-peptide. The GH level in six MD patients responded normally to GHRH (group I), with a peak of 17.1 +/- 1.46 micrograms/l, compared with controls (27.8 +/- 19.6 micrograms/l, NS), and that in the other six patients responded subnormally, with a peak of 3.15 +/- 1.46 micrograms/l, lower than in controls and in group I patients (P < 0.001). In group I the insulin response to the glucose tolerance test showed hyperinsulinism and was lower than that in group II patients; stimulated C-peptide was also higher in group II than in group I and in controls; urinary C-peptide levels were parallel to those in previous data. In all MD patients there were a negative correlation between absolute values of GH response to GHRH and insulin response to glucose tolerance test (r = -0.79, P < 0.001). Our data suggest that the failure in GH release and peripheral insulin action is due to a generalized defect in cellular membrane function in MD patients. PMID- 7981581 TI - High-dose intravenous melphalan in a patient with multiple myeloma and oliguric renal failure. AB - A kappa light-chain myeloma was diagnosed as the underlying disease in a 52-year old woman with acute oliguric renal failure. The patient was erroneously treated with high-dose intravenous melphalan (60 mg/m2). Because of this overdose treatment with granulocyte colony-stimulating factor was initiated, but pronounced absolute leukopenia (white blood cell count < 0.5 x 10(9)/l) developed and lasted for 13 days. Following melphalan treatment a continuous increase in urine volume was accompanied by a decrease of serum creatinine and blood urea nitrogen. Within 10 days after the administration of melphalan the patient no longer required hemodialysis. We conclude that high-dose chemotherapy in combination with hematopoietic growth factors should be considered in individual cases with newly diagnosed light-chain nephropathy. PMID- 7981580 TI - Iron-deficiency anemia as the sole manifestation of celiac disease. AB - We report on a 40-year-old woman with a 2-year history of iron-deficiency anemia of unknown origin. Repeated endoscopic investigations in the past had revealed no abnormality of the gastrointestinal system on macroscopic examination. Oral iron supplementation was shown to have no effect on serum iron levels and had no influence on the anemia. Upper gastrointestinal endoscopy performed at our hospital confirmed normal macroscopic findings. However, jejunal biopsies revealed subtotal villous atrophy of the mucosa of the small intestine. A strict gluten-free diet led to an increase in serum iron, resolution of the anemia, and restitution of normal mucosal architecture. Thus iron-deficiency anemia may be the lone manifestation of celiac disease. PMID- 7981583 TI - Cell-type specific response of peripheral blood lymphocytes to methotrexate in the treatment of rheumatoid arthritis. AB - The mode of action of methotrexate in the treatment of rheumatoid arthritis is still questionable. Although in vitro results suggest an immunosuppressive effect of methotrexate, several clinical studies have failed to confirm these effects in patients treated with oral low-dose methotrexate. With respect to the highly variable bioavailability of methotrexate, we investigated the effects of an intravenous administration of 15 mg methotrexate per week on peripheral blood lymphocyte subsets in eight patients with rheumatoid arthritis. Methotrexate after 12 weeks significantly (P < 0.01) reduced total peripheral blood lymphocytes and led to a pronounced redistribution of lymphocyte subsets with a preferred reductive effect on B-lymphocytes (P < 0.005) and T-lymphocytes (P < 0.05). Natural killer cells and killer cell-like T cells, on the other hand, were unaffected by the treatment. Our results suggest a cell-type specific effect of intravenously administered low-dose methotrexate on peripheral blood lymphocytes. This effect, in our opinion, may contribute to the mode of action of methotrexate as an immunosuppressive drug in the treatment of rheumatoid arthritis. PMID- 7981582 TI - Cytokine-based biotherapy of gastrointestinal tumors. AB - Over the past 20 years the administration of cytokines has emerged as an important fourth modality for the treatment of human cancer. Advances in the field of therapy of gastrointestinal tumors have become a major focus of current research, given the lack of progress of conventional antineoplastic therapy in most of these tumors. Among the heterogeneous group of gastrointestinal malignancies, novel therapeutic strategies have been employed for each individual tumor type, and cytokines (interferon-alpha) have gained an established role in the treatment of advanced carcinoid tumors. Although our understanding of the mechanisms of biological response modification is still limited, further improvement in the management of gastrointestinal malignancies can be expected from multimodality therapy regimens employing cytokines in combination with other biological response modifiers, chemotherapeutic agents, active-specific immunotherapy, and immunotoxin- and radionuclide-conjugated monoclonal antibodies. A wide range of clinical and preclinical studies have been conducted in colorectal carcinoma; however, potential therapeutic benefit of cytokine-based biotherapy has not been fully defined. Therefore, largescale, i.e., multicenter, studies are required to quantify the potential therapeutic effects of cytokines in gastrointestinal tumors. PMID- 7981585 TI - Identification of a 7-basepair deletion in the adenine phosphoribosyltransferase gene as a cause of 2,8-dihydroxyadenine urolithiasis. AB - We describe a family of Turkish origin with adenine phosphoribosyltransferase (APRT) deficiency and renal stone disease. The proband had 2,8-dihydroxyadenine urolithiasis but an older sister, who was also deficient in enzyme activity, is so far asymptomatic. The proband was homozygous for a 7-bp deletion in exon 3 of the APRT gene. One allele from each of the parents also contained this deletion. The patient and her father were homozygous for an intragenic TaqI RFLP (1.25-kb fragment) whereas the mother was heterozygous (1.25- and 1.91-kb fragments), indicating that the mutation was present on the allele carrying the 1.25 kb TaqI fragment. The deletion alters the reading frame downstream of codon 93 and would be expected to abolish enzyme activity. PMID- 7981584 TI - A comparative study on antibodies to nucleoli and 5-hydroxytryptamine in patients with fibromyalgia syndrome and tryptophan-induced eosinophilia-myalgia syndrome. AB - Eosinophilia myalgia syndrome (EMS) has been related to intake of "contaminated" L-tryptophan, and an alteration in tryptophan 5-hydroxytryptamine (5-HT, serotonin) metabolism has been reported in EMS patients. Recently we found that a defined autoantibody pattern consisting of antibodies to nucleoli, gangliosides, and phospholipids is closely related to the fibromyalgia syndrome (FS) which clinically resembles the EMS. We were therefore interested to see whether these antibodies can also be detected in patients with EMS. Studied were 27 patients with acute EMS (13 of whom were also examined 2 years after acute onset), 100 patients with FS, and 40 patients with progressive systemic sclerosis (PSS). As controls, sera from 100 blood donors were analyzed. Antibodies to nucleoli were demonstrated by immunofluorescence test on cell cultures in 52% of patients with acute EMS, 62% of patients with chronic EMS, and 37% of FS patients. Western blotting with a nuclear extract from HeLa cells revealed in both diseases the same epitopes at 63, 57, and 53 kDa. Antibodies to 5-HT, gangliosides (Gm1), and phospholipids were determined by enzyme-linked immunosorbent assay. Among patients with FS 73% had antibodies to 5-HT, in contrast to only 19% of patients with acute EMS. However, 77% of the 13 EMS patients analyzed 2 years later had become anti-5-HT antibody positive during that time. Also the incidence of antibodies to Gm1 increased from 37% at acute onset to 69% in patients with chronic EMS (30%). The various antibodies were detected in only 18% of healthy controls.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7981586 TI - Some unanswered questions in Duchenne muscular dystrophy. AB - Though the molecular and biochemical bases of Duchenne muscular dystrophy are known, many questions still remain unanswered. They range from the nature and cause of gene deletions to the relationship between dystrophin defects and the clinical phenotype, both in affected males and female carriers. These questions are discussed in the light of recent developments. PMID- 7981587 TI - Dystrophin deficiency, altered cell signalling and fibre hypertrophy. AB - Dystrophin is a subsarcolemmal protein which is defective in Duchenne and Becker muscular dystrophy (DMD/BMD), and in three animal models. Clinical manifestations of dystrophin deficiency in humans range from a mild calf muscle hypertrophy with cramps to the classical progressive degenerative hypertrophic myopathy of Duchenne. A common feature in the clinical presentation of dystrophin deficiency in humans and in the three documented animal models is the presence of muscle fibre hypertrophy. This paper explores the hypothesis that membrane-bound signalling processes are disrupted in the absence of dystrophin, and suggests that these abnormalities may contribute to both the hypertrophic and degenerative changes of dystrophin deficiency. PMID- 7981588 TI - Innervation of MyoD-converted human amniocytes and fibroblasts by fetal rodent spinal cord neurons. AB - MyoD is one member of a gene family involved in the regulation of myogenesis. MyoD transfection induces myogenesis in a variety of non-muscle cells. Human amniocytes and fibroblasts were infected with a MyoD-retrovirus vector, to determine whether the converted cells can mature normally to form functional muscle fibers. MyoD-converted cells were cocultured with fetal rat spinal cord. After 2-3 weeks of co-culture cross-striated, contracting muscle fibers were observed. Combined acetylcholinesterase cytochemistry and acetylcholine receptor labeling showed prominent staining at nerve-muscle contacts. Approximately half of the total creatine kinase activity was due to the muscle-specific isozyme. Innervated MyoD-converted cells might represent a new source of muscle cells for studying the molecular events leading toward the formation of functional muscle. This system also appears suitable for studying the pathogenesis of hereditary, often rare, myopathies affecting muscle-specific proteins, for which muscle tissue is frequently unavailable for in vitro analysis. PMID- 7981589 TI - Dystrophin-deficient myofibers are vulnerable to mast cell granule-induced necrosis. AB - Duchenne muscular dystrophy is the most common inherited lethal X-linked disorder of mankind and is caused by dystrophin deficiency. The steps involved in the dystrophin-deficiency-induced cascade which lead to myofiber necrosis, progressive muscle wasting in humans and dogs and prominent muscle hypertrophy in mice and cats are obscure. Dystrophin is an intracellular component of the membrane cytoskeleton and its absence would be expected to cause necrosis of isolated myofibers (cell autonomous defect). However, all dystrophin-deficient muscles characteristically show simultaneous degeneration of large groups of muscle fibers (grouped necrosis). This implies that cell death may be mediated by extracellular, non-cell autonomous factors which occur as a secondary consequence of dystrophin deficiency. We have proposed a model where tissue pathology may be mediated by infiltrating mast cells (Gorospe et al., J Neurol Sci 1994). Here we show that intramuscular injections of purified mast cell granules induce widespread myofiber necrosis in dystrophin-deficient mdx mice, but not in normal mice. These data support the hypothesis that dystrophin acts as a plasma membrane stabilizer and that its deficiency renders myofibers more susceptible to damage from mast cell proteases. Moreover, our results support the hypothesis that mast cell degranulation may be a trigger for myofiber death in dystrophin-deficient muscle. PMID- 7981590 TI - A possible missense mutation detected in the dystrophin gene by Double-Strand Conformation Analysis (DSCA). AB - A new and simple method for detecting point mutations is presented. The method, based on Double-Strand Conformation Analysis (DSCA) of PCR amplification products in polyacrylamide gel electrophoresis, was applied to 78 unrelated subjects affected with Duchenne or Becker muscular dystrophy and to 9 subjects suspected to be affected with an atypical dystrophinopathy. An A-->G substitution in the nucleotide 2525, which changes the codon for lysine to a codon for glutamic acid was detected in an 8-year-old boy, with normal neurological examination, but showing increased CK level and an abnormal EMG. The muscle biopsy was normal, without features of necrosis or regeneration. Immunoreactions with anti dystrophin antibodies showed a normal distribution and intensity of the staining. A review of the dystrophin mutations detected so far is included. PMID- 7981591 TI - Expression of dystrophin-associated glycoproteins during human fetal muscle development: a preliminary immunocytochemical study. AB - An immunocytochemical study was performed on quadriceps muscle from eight fetuses ranging from 12 weeks of gestation to term, using antibodies against the dystrophin-associated proteins, in order to evaluate the developmental expression of these proteins. For comparison, antibodies against dystrophin and utrophin were also used. The expression of the 59 kDa dystrophin-associated protein was simultaneous with that of dystrophin, which is also a subsarcolemmal protein. The extracellular glycoprotein of 156 kDa (alpha-dystroglycan) and the transmembrane glycoprotein of 43 kDa (beta-dystroglycan) appeared to be expressed later. The transmembrane glycoproteins of 50 kDa (adhalin) and 35 kDa were fully expressed at an even later stage of fetal muscle development. This study suggests that the subsarcolemmal proteins may have an essential role in the assembly of the transmembrane and extracellular components of the dystrophin-glycoprotein complex during fetal muscle development. The knowledge obtained from observing the developmental expression of these proteins may contribute to the understanding of the molecular mechanism of their different involvement in muscle disorders. PMID- 7981593 TI - Cognitive impairment in Duchenne muscular dystrophy. AB - Cognitive function and dystrophin gene mutations were investigated in 50 DMD patients (mean age 11.1 yr; range 3.5-20.3). General intelligence assessment showed 31% of patients with Wechsler full intelligence quotient (FIQ) lower than 75 (normal values: 100 +/- 14), and only 24% with appropriate FIQ level. Modal distribution of Wechsler verbal, performance, and FIQs, and Raven IQs was normal. Verbal IQ was more affected than performance IQ (PIQ) only in the younger group of subjects. Low PIQ correlated with the presence of macroglossia, detected in 13 out of 50 patients. Impairment of productive language was of non-dysphasic nature and correlated with defects of short-term memory, which was also affected in non verbal skills. DMD patients shared the same spectrum of neuropsychological defects, regardless of whether they were or were not mentally retarded. The proportion of patients with dystrophin gene deletions was 64%. No statistically significant correlations were found between genetic data and psychometric assessment. Finally, (18F)-fluorodeoxyglucose positron emission tomography studies demonstrated cerebellar hypometabolism in all the DMD patients examined and variable involvement of associative cortical areas. These findings suggest a possible role of the cerebral and cerebellar hypometabolism in the cognitive impairment of DMD. PMID- 7981592 TI - Clinical-molecular correlation in 104 mild X-linked muscular dystrophy patients: characterization of sub-clinical phenotypes. AB - A multidisciplinary study was conducted in order to assess dystrophin expression in a large series of mild X-linked muscular dystrophy patients, with well-defined clinical phenotype. Patients (104) were divided in 4 clinical groups, according to clinical severity: asymptomatic (sub-clinical), benign, moderate and severe, Cardiopathy was also assessed, and dilated cardiomyopathy was found in 47% of sub clinical and benign cases. Myoglobinuria, cramps and myalgia were also associated with a sub-clinical or benign clinical status. Dystrophin immunohistochemical pattern of labelling and dystrophin amount decreased gradually across clinical groups. Our study showed a significative correlation between: (1) dystrophin amount and immunohistochemical score (p < 0.05); (2) dystrophin amount and clinical score (p < 0.05). Therefore, the combined use of these different techniques for prognosis of mild X-linked muscular dystrophy patients is useful. Our study assesses the prevalence of the various disease courses in a large cohort of mild X-linked muscular dystrophy patients. From our series, up to 30% of patients may be either asymptomatic or have sub-clinical changes. PMID- 7981594 TI - Mutation of dystrophin gene and cardiomyopathy. AB - The correlations between the type of gene mutation and the cardiac clinical picture were examined in 284 patients with dystrophinopathy (200 Duchenne and 84 Becker). The subjects with normal heart showed deletions including exons 48-49 in 21.4% DMD and in 25% BMD, and other deletions in 35.7% DMD and 25% BMD; vice versa the cases with severe cardiac involvement showed deletions including 48-49 in 38.8% DMD and 37.5% BMD and other deletions in 32.9% DMD and 20% BMD. The age of death was 18 years in DMD patients with deletions including 48-49 whereas the age was about 22 in the cases with other deletions. The differences were statistically significant. PMID- 7981595 TI - Prevalent cardiac involvement in dystrophin Becker type mutation. AB - Myocardial involvement is frequently present in Xp21-linked muscular dystrophy, due to a lack of dystrophin in cardiac fibres. We describe a 41-yr-old man affected by dilated cardiomyopathy with sporadic episodes of myoglobinuria induced by effort and increased levels of serum creatine kinase. Very mild signs of skeletal myopathy were clinically evident. His mother was affected by an indefinite cardiopathy and suddenly died when she was 36 yr old. Muscle biopsy of the patient showed a dystrophic process. Dystrophin analysis together with a genetic DMD locus study led us to diagnose Becker type muscular dystrophy, with truncated dystrophin and a gene deletion extending from exon 45 to 48. Prevalent cardiac involvement in a Becker type mutation of the dystrophin gene further confirms clinical variability of dystrophinopathies. PMID- 7981597 TI - Neuromuscular disorders: gene location. PMID- 7981598 TI - Mitochondrial encephalomyopathies: gene mutation. PMID- 7981596 TI - Dystrophinopathy presenting as congenital muscular dystrophy. AB - We report a 3 1/2-year-old boy with congenital hypotonia, calf pseudohypertrophy, markedly delayed motor milestones and joint contractures. He was initially diagnosed to have congenital muscular dystrophy on the basis of the age of onset, a myopathic EMG, an elevated creatine kinase and a dystrophic muscle biopsy. Subsequently, dystrophin immunocytochemistry and immunoblot analysis showed complete absence of dystrophin. We suggest that male cases of CMD should undergo dystrophin analysis, if there is calf hypertrophy and markedly elevated CK (> 2000 U/l). PMID- 7981599 TI - Methods for the detection of apoptosis. AB - Apoptosis is central to many basic and clinically oriented investigations, and this article is a brief overview of the most frequently utilized methods for detection of apoptotic cells, including the study of morphology, analysis of DNA degradation, DNA end labeling techniques, flow cytometric analysis, and nuclease assays. Features and advantages of the different methods are discussed. PMID- 7981601 TI - Multi-step chromatin degradation in apoptosis. DNA breakdown in apoptosis. AB - Elucidation of the mechanism and regulation of cell destruction in apoptosis requires knowledge of genome degradation. The cell genome, which encodes the fundamental cell programmes, is most likely to be the main sensitive target in cell apoptosis. Genome breakdown may be achieved by the generation and transduction of apoptogenic signal information to the specific chromatin regions of the nucleus, thus inactivating the basic cell programmes and inducing the endogenous pattern of chromatin degradation, which is determined by the genome organization of the eukaryotic nuclei. Detachment of chromatin from the nuclear matrix attachment regions may be one of the possible mechanisms of switching off the genome function and triggering the multi-step process of endogenous chromatin degradation, thus leading to cell death of terminal differentiation or stress induced apoptosis. PMID- 7981600 TI - Role of nucleases in apoptosis. AB - The last decade has seen the rapid development of research investigating the mechanisms of apoptosis in a variety of experimental systems. Among the multitude of changes observed in apoptotic cells, chromatin cleavage is considered a biochemical hallmark of apoptosis. Chromatin fragmentation is an enzymatic process which depends on the activity of endogenous nuclease(s) and the susceptibility of chromatin to endonuclease activity. The characteristics of some nucleases of potential importance in apoptosis and their possible role in the regulation of this process are discussed in this paper. PMID- 7981602 TI - Molecular characterization of the Nur77 orphan steroid receptor in apoptosis. AB - One of the in vitro model of programmed cell death is T cell receptor (TCR) mediated apoptosis of immature T cells and T cell hybridomas. This form of apoptosis requires newly gene synthesis and may relate to negative selection during T cell development. Recently, an orphan steroid receptor Nur77 was found to be induced during TCR-mediated apoptosis. When introduced into T cells, a dominant negative or antisense Nur77 construct can block the apoptosis process. Various inhibitors of TCR-mediated apoptosis, including cyclosporin A down regulate the Nur77 DNA binding activity. Thus, the Nur77 protein family may play a crucial role during T cell apoptosis. PMID- 7981603 TI - Glucocorticoid-induced apoptosis of lymphoid cells. AB - The induction of cell death in lymphoid cells by glucocorticoids is one of the earliest and most thoroughly studied models of apoptosis. Although the exact mechanism by which apoptosis occurs in lymphocytes is unknown many biochemical and molecular changes have been shown to occur in these cells in response to glucocorticoids. The role of chromatin degradation and endonucleases in the apoptotic process has been closely studied, as well as the involvement of several oncogenes in glucocorticoid-induced cell lysis. In addition, the clinical importance of glucocorticoid-induced apoptosis in the treatment of lymphoid neoplasms has recently received increased attention. PMID- 7981604 TI - To be or not to be: mutually antagonistic death signals regulate thymocyte apoptosis. AB - Recognition of self-antigens by immature thymocytes results in either activation induced apoptosis (negative selection) or survival (positive selection). While it is believed that T cell receptor avidity plays a role in determining the outcome, the mechanisms responsible for this life or death decision are not known. Recent data concerning the mutual antagonism between activation- and glucocorticoid induced apoptosis have prompted an examination of the potential interaction of these two signaling pathways in the regulation of antigen-specific selection. PMID- 7981605 TI - Role of bcl-2 and apoptosis in viral infections. AB - For decades immunobiologists have focussed on lymphocyte activation leading to cellular proliferation as a means by which the numbers of antigen-responsive cells can be increased. The pendulum has now swung back and questions are being raised about the way in which the size of the activated lymphocyte populations, such as those found during certain acute viral infections, can be controlled. The process of apoptosis has gained widespread recognition as a physiological means by which unwanted cells can be removed. In this review we will discuss recent observations on the control of apoptosis in the activated and expanded T cell populations found during viral infections and how this process co-exists with certain mechanisms which enable the retention of the fittest cells which can participate in subsequent encounters with virus. PMID- 7981606 TI - Tumor development and apoptosis. AB - Apoptosis or other types of active cell death may play a major role at various stages of carcinogenesis. Active cell death can be induced, by internal and exogenous signals, in preneoplastic, neoplastic and even malignant cells. It may reverse the effects of initiation and promotion and may lead to tumor regression. Conversely tumor promoters may inhibit active cell death in preneoplastic cells and thereby accelerate cancer development. PMID- 7981607 TI - Apoptosis and therapy of malignant diseases of the hematopoietic system. AB - Apoptosis is essential in the pathogenesis of hematological diseases. A tumor develops, if the balance between cell division and cell death is disturbed. In recent years many genes involved either in blocking or inducing this process have been identified. Additionally, several cytokines which influence apoptosis have been found. Some of these cytokines could also play a role in the development of resistance to chemotherapeutic agents. Many anticancer drugs exert their action via apoptosis. A strategy to selectively induce apoptosis of tumor cells without altering healthy cells and thus reducing the side effects of therapeutic regimens is a major goal for future development of new therapeutic techniques. Blocking the factors which are responsible for resistance is another promising therapeutic approach and could further improve the clinical outcome and finally prolong the life of patients. PMID- 7981608 TI - Fibroblasts determine the fate of Fc epsilon RI+ cell populations in vitro by selectively supporting the viability of mast cells while internalizing and degrading basophils. AB - To determine the fate of Fc epsilon RI+ cells on fibroblasts in vitro, human bone marrow derived CD34+ cells were cultured in the presence of recombinant human interleukin 3 and recombinant human hematopoietic stem cell factor for 3 weeks, and Fc epsilon RI+ cells were purified by immunomagnetic selection. This enriched Fc epsilon RI+ cell population consisted of 92-94% basophils and 3-5% mast cells as determined by morphologic, immunohistochemical, and ultrastructural criteria. The Fc epsilon RI+ cells were then cocultured with 3T3 fibroblasts. Basophils decreased markedly by 1 week and were absent from cocultures by 2-3 weeks, while the mast cell numbers on the fibroblast monolayers remained constant. Ultrastructural examination of cocultures at 2 days demonstrated phagocytosis of basophils by fibroblasts. By 1 week, phagocytosed basophil membranes and granules gave fibroblasts the superficial appearance of mast cells by toluidine blue staining. Mast cells surviving in cocultures could be distinguished from granule containing fibroblasts by IgE surface labeling and by ultrastructural demonstration of tryptase-positive granules. Thus, while mast cells remain viable in coculture with 3T3 fibroblasts, basophils do not survive and are internalized and degraded by the fibroblast monolayer. PMID- 7981609 TI - Immune response against ovalbumin in rats colonized with an ovalbumin-producing Escherichia coli and the influence of feeding ovalbumin. AB - The influence of feeding ovalbumin (OA) on the development of IgE/IgG antibodies and delayed-type hypersensitivity (DTH) against OA was studied in rats colonized from birth with an Escherichia coli genetically manipulated to produce OA. At 21 days of age, colonized pups and pups with a normal intestinal flora were weaned onto either an OA-containing or a conventional diet without OA. At 2 months of age the colonized rats showed an increased DTH reaction to OA, but they did not have any anti-OA antibodies in serum. The rats were then immunized intracutaneously with OA in Freund's complete adjuvant. After immunization the colonized rats fed the conventional diet had a significantly higher DTH reaction to OA and significantly higher serum levels of IgE anti-OA antibodies than the uncolonized rats on the same diet. The colonized rats eating the OA-containing diet showed a 73% decrease in the DTH reaction to OA and also significantly lower levels of IgE and IgG antibodies against OA compared with the colonized rats fed conventional diet. The dams colonized as adults by the OA-producing E. coli developed IgE anti-lipopolysaccharide antibodies in serum while the pups colonized via the dams at birth did not. Neonatal colonization with an E. coli strain producing OA resulted in increased DTH reactivity against OA and priming for secondary IgE anti-OA response. Feeding the animals an OA-containing diet from weaning abrogated this intestinally induced hypersensitivity and rendered the animals orally tolerant to OA. PMID- 7981610 TI - Circadian patterns in histamine concentrations and mast cell number in the rat thyroid gland. AB - We carried out a cross-sectional chronobiological investigation on blood histamine, thyroid histamine and thyroid mast cell number in Wistar rats. Daily, blood histamine varied from 0.38 +/- 0.01 (12.00 h) to 0.60 +/- 0.01 mg/g wet weight (20.00 h) and thyroid histamine from 21.2 +/- 1.19 (04.00 h) to 38.3 +/- 1.54 mg/g wet weight (08.00 h). The number of mast cells per microscopic field ranged from 10.8 +/- 0.6 (16.00 h) to 14.6 +/- 0.6 (12.00 h) in males and from 8.3 +/- 0.2 (04.00 h) to 14 +/- 0.4 (12.00 h) in females. Chronobiologic analysis indicates that the levels of all three variables follow a circadian pattern with a period of 12 h. Peak levels were noted at 07.36 h and 19.36 h for the blood histamine concentration, at 09.00 and 21.00 h for the tissue histamine concentration, and at 11.00 and 23.00 h for the mast cell number. The consistent, consecutive relationship of these data supports the hypothesis that thyroid mast cell number is conditioned by the blood histamine level and thyroid histamine concentration. PMID- 7981611 TI - Analysis of human T cell clones reactive with group V grass pollen allergens. AB - Twenty-seven T cell clones (TCC) reactive with group V allergens of Phleum pratense (Phlp V) were established from the peripheral blood of 3 patients allergic to grass pollen. Twenty-four TCC showed the helper cell phenotype CD3+, CD4+, CD8-; the remaining clones were CD3+CD4-CD8+. T cell recognition of Phlp V was exclusively HLA-DR restricted. Many of the Phlp V reactive TCC (19 of 27; 70%) were stimulated additionally by other group V allergens isolated from Lolium perenne, Poa pratensis, and Dactylis glomerata. These data indicate the existence of cross-reacting T cell epitopes among group V allergens of different grasses. The Phlp V triggered cytokine production demonstrated in 13 out of 24 CD4+ TCC a Th2-like pattern (high interleukin 4/gamma-interferon ratios) suggesting group V allergens as important targets of grass pollen specific IgE. PMID- 7981612 TI - Determination of interleukin 6 in human urine and epithelial cell supernatants. AB - Interleukin 6 (IL-6) is a cytokine with many biological functions. It is produced by different tissues in response to infection and is secreted into the local body fluids. The aim of this study was to find a suitable assay to measure IL-6 in human urine. IL-6 was quantitated by a bioassay and by immunoassays based on neutralizing or nonneutralizing antibodies. The effect of human urine on the quantitation of IL-6 by these assays was analyzed using pooled human urine with added recombinant or natural human IL-6. Urine was found to disturb the growth of the B9 cells. When fractions from gel-filtered human urine were tested, a fraction corresponding to a protein molecular weight range of 10,000-1,000 was found to have a strong inhibitory effect in the B9 assay. In contrast, the low molecular weight fractions containing salts and pigments were not found to disturb the assay. The inhibitory effect of urine was avoided by diluting the samples > 80 times (final dilution in the test plate) or by dialysis. Furthermore, we analyzed IL-6 in urine samples from patients with urinary tract infection and supernatants from epithelial cells stimulated with bacteria in vitro. The B9 assay and the immunoassay based on non-neutralizing anti-IL-6 antibodies were more sensitive than the immunoassays based on neutralizing antibodies. While most of the B9 activity in the urine samples and supernatants could be neutralized by anti-IL-6 antibodies, some samples contained unneutralizable activity. These components remain to be defined. The results demonstrate considerable variation between assays used to quantitate natural IL 6. PMID- 7981613 TI - Remission of sarcoidosis following removal of silicone gel breast implants. AB - We report herein a patient with debilitating multisystem sarcoidosis. Interestingly, dermal lesions and enlarged lymph nodes resolved and her clinical condition dramatically improved following removal of silicone gel breast implants. Of note, the capsular tissue surrounding the breast implant demonstrated a granulomatous foreign-body response. The potential harmful effects of silicone may include an acceleration of an already existing hypersensitivity response. PMID- 7981614 TI - Thimerosal induces toxic reactions. PMID- 7981615 TI - Symposium on tyrosine protein kinases and cell signalling. Mont Sainte Odile, Alsace, France, September 24-27, 1993. Selected contributions. PMID- 7981616 TI - Protein kinases share a common structural motif outside the conserved catalytic domain. AB - A comparison of the sequences of the mammalian and Dictyostelium catalytic subunits of cAMP-dependent protein kinase revealed extensive sequence similarities through the catalytic core and the carboxy terminal tail. The amino terminal sequences however differ dramatically. The large difference in size, 73 kDa for the Dictyostelium enzyme versus 40 kDa is due to an extension in the N terminus. The mouse enzyme has at its amino-terminus a long amphipatic helix, the A-helix, that precedes the catalytic core, covering the surface of both lobes of the enzyme. Dictyostelium does in fact, have a similar motif but it is remote from the catalytic core, in the N-terminal extension. On the basis of molecular modeling, it is proposed that residues 77-98 correspond to a structural motif similar to the A-helix in mouse catalytic subunit. Sequences encoding similar putative motifs contiguous to the catalytic core can be recognized in many other protein kinases and is particularly prominent in all of the non-receptor tyrosine kinases. In the case of Src, this A-helix motif appears to serve as the linker between the conserved catalytic core and the SH2 domain. The interaction between the A-helix motif and the core is described, and the general occurrence of this structure within the protein kinase family is discussed. PMID- 7981617 TI - Hepatocyte growth factor and its receptor, the tyrosine kinase encoded by the c MET proto-oncogene. AB - HGF is secreted by mesenchymal cells and regulates motogenesis, mitogenesis, and morphogenesis of epithelial and endothelial cells. HGF is a heterodimer of two glycosylated chains, alpha and beta, bound together by a disulfide bond. The molecule is synthesized as single chain precursor devoid of biological activity (pro-HGF). The critical step in pro-HGF activation is a proteolytic cleavage generating the two chain form. This step occurs in the extracellular environment, and is catalyzed by urokinase. Two alternative transcripts originate two HGF variants. One bears a deletion of five amino acids in the alpha chain, and has the same properties of the full-size protein. The other one contains only the first portion of the alpha chain (two kringle HGF). Two kringle HGF binds the HGF receptor, triggers its tyrosine kinase activity and behaves as a partial agonist, inducing motogenesis but not mitogenesis in target cells. The HGF receptor is the tyrosine kinase encoded by the c-MET pro-oncogene, a tyrosine kinase receptor. This molecule is an heterodimer of an extracellular alpha chain disulfide linked to a transmembrane beta chain. The cytoplasmic portion of the beta chain contains the catalytic domain and critical sites for the regulation of its kinase activity. In the C-terminal tail, a bidentate motif containing two tyrosines associates the transducers responsible for HGF signalling. PMID- 7981618 TI - P56lck A lymphocyte specific protein tyrosine kinase: activation, regulation and signal transduction. AB - p56lck, a src family protein tyrosine kinase interacts with several T cell receptors, like: CD4, CD8, CD2 and the beta-chain of the IL2, thereby receptors devoid of kinase activity may transduce signals via tyr phosphorylation. Tyr 192 and ser 194, located in the SH2 domain of p56lck is phosphorylated upon CD3 triggering, which can change interactions of tyr-P proteins with this SH2 domain. Upon activation through the CD2 or the CD45 receptors the kinase activity of p56lck is temporarily increased. By immunofluorescent and confocal microscopy we observed that a significant proportion of p56lck and CD2 receptors are localized in endosomal vesicles after stimulation. By Western blot we showed a parallel recruitment of the PTK p70-ZAP in this vesicles. The role of p56lck away from the plasma membrane localized in vesicles is under study. PMID- 7981619 TI - Nuclear translocation of phosphatidylinositol 3-kinase in rat pheochromocytoma PC 12 cells after treatment with nerve growth factor. AB - Immunocytochemical analysis of PI 3-kinase localization in PC 12 cells demonstrates that the enzyme translocates to the nucleus after cell treatment with differentiating doses of NGF. The association of PI 3-kinase to the nucleus occurs rapidly (within minutes) and increases with the time of exposure of NGF. We suggest that PI-3 kinase specific localization may determine the production of novel phosphoinositides in cell compartments targeted to effect diverse cell responses. The nuclear translocation is consistent with accumulating data on the existence of a nuclear inositol lipid cycle which could also include 3 phosphorylated inositides, participating to the modulation of the cell response to extracellular stimuli. PMID- 7981620 TI - Overproduction of bacterial chaperones improves the solubility of recombinant protein tyrosine kinases in Escherichia coli. AB - The production and purification of recombinant proteins from E. coli expression systems is often complicated by the fact that a significant amount of the foreign protein is deposited in the cytoplasm of the bacteria as aggregates or inclusion bodies. Many non-receptor protein tyrosine kinases are typical examples of proteins that are poorly soluble when overproduced in E. coli. Here, we report on the engineering of bacterial strains which overproduce chaperone proteins of the Hsp70 (DnaK, DnaJ and GrpE) and Hsp60 (GroEL and GroES) families. The simultaneous overproduction in E. coli of the chaperones DnaK, DnaJ and GrpE on the one hand, or GroEL and GroES on the other hand, and the human non-receptor protein tyrosine kinases Csk, Fyn or Lck resulted in increased solubility of the recombinant kinases. This provides the basis for future successful production and purification of large quantities of soluble and active non-receptor protein tyrosine kinases from E.coli expression systems and will enable the further characterization of these important enzyme families at the molecular level. PMID- 7981621 TI - Thrombin-induced redistribution of protein-tyrosine-phosphatases to the cytoskeletal complexes in human platelets. AB - Human platelets provide an attractive model for studying the regulation of tyrosine phosphorylations and cell-cell adhesion. Major non-receptor tyrosine kinases are suggested to be responsible for an increase in protein tyrosine phosphorylation following platelet stimulation. Agonist-induced platelet activation triggers also the reorganization of the cytoskeleton with association of multiple signalling proteins. To understand if protein-tyrosine-phosphatases (PTPs) were involved in platelet aggregation, we have investigated the subcellular distribution of these enzymes in resting and thrombin-stimulated platelets. A high level of PTP activity in human resting cells is distributed for 65% and 35%, respectively, in cytosolic and particular fractions. About 10% of this activity are redistributed to the cytoskeletal network during platelet activation. This translocation is dependent on actin polymerization as proved by the disappearance of this phenomenon in cells pretreated by cytochalasin D. Moreover, immunoblotting using anti-PTP polyclonal antibodies indicates that two PTPs, SH-PTP1 and p58 related to HPTP beta, translocate from membranes to Triton X-100 insoluble fractions after platelet activation. This translocation is correlated with the redistribution of several signalling proteins suggesting the possible regulation between these molecules and PTPs. PMID- 7981622 TI - Implication of a protein-tyrosine-phosphatase in human lung cancer. AB - Protein tyrosyl phosphorylation plays an essential role in regulating cellular events such as proliferation, differentiation and oncogenesis. The recent characterization of the family of protein tyrosine phosphatases (PTPases) suggests that dephosphorylation might be a crucial event in these phenomena. One of the functions of PTPases is to reverse the effect of protein tyrosine kinases (PTKases), many of which are oncogenes, suggesting that they may act as tumor suppressors as described for HPTP gamma. In order to investigate the implication in lung cancer of HPTP beta, a receptor PTPase, we have developed a semi quantitative method derived from primer-directed reverse transcription (RT) and subsequent polymerase chain reaction (PCR) with 32P-labelled nucleotide. We have demonstrated that the expression of HPTP beta mRNA was dramatically decreased in lung adenocarcinomas and lung malpighian carcinomas as compared to normal lung tissue. In addition, HPTP beta was not expressed in the pulmonar adenocarcinoma cell line A427, which proliferates in a deregulated way. These results suggest that the loss of expression of HPTP beta might play a role in neoplasic transformation and thus this molecule could act as a tumor suppressor factor. PMID- 7981623 TI - Rapid and transient translocation of PLC-gamma 1 to the cytoskeleton of thrombin stimulated platelets. Evidence for a role of tyrosine kinases. AB - Cytoskeleton reorganization has been suggested to play an important role in platelet signal transduction. A number of signalling molecules are found to relocalize to this fraction upon thrombin stimulation. In this paper, we show that PLC-gamma 1, a key enzyme of the inositol lipid metabolism, is also translocated to the platelet cytoskeleton upon thrombin stimulation. Interestingly, its translocation is very rapid and transient, and correlates with the increase in PLC activity previously measured in the cytoskeleton by our group. Using a potent tyrosine kinase inhibitor, tyrphostin AG-213, we show a significant inhibition of the translocation of PLC-gamma 1, indicating an involvement of tyrosine kinases in its relocation. Thus, our results demonstrate for the first time a rapid and transient tyrosine kinase-dependent translocation of PLC-gamma 1 to the cytoskeleton of thrombin-stimulated platelets. PMID- 7981624 TI - Annexin 1 regulation in human epidermal cells. AB - Annexin 1 (named p35, lipocortin I or calpactin II), initially described as a glucocorticoid induced protein, belongs to a new characterized family of intracellular proteins. In the skin, the role of annexins has still not been elucidated. In a previous study, we reported the localization of annexin 1 in both freshly isolated human epidermal cells and in cultured keratinocytes using immunofluorescence, FACS analysis and immunoblotting techniques. The protein was characterized by Western blot and immunoprecipitation as a 35 kDa protein. Results from in vivo studies confirmed the presence of annexin 1 in basal and suprabasal layers of normal human skin with modified reactivity patterns in hyperproliferative lesions. In the present study, the role of glucocorticoids in annexin 1 regulation was investigated in epidermal cells by Western blot and immunoprecipation assays. In contrast to other studies, we found that glucocorticoid treatment of epidermal cells led to a decrease in annexin 1 content in the cytoplasm and the membranes of cells. As annexin 1 was not detected in the nucleus of cells, we conclude that there was a down regulation of annexin 1 after glucocorticoid treatments rather than a translocation of the protein to the nucleus. Despite the absence of the signal peptide sequence necessary for protein secretion, annexin 1 was released in the keratinocyte culture medium. We found that the protein was secreted only in low Ca2+ medium (0.15 mM), this process required an active metabolism. PMID- 7981626 TI - Glucocorticoids antagonize retinoic acid stimulation of PEPCK gene transcription in 3T3-F442A adipocytes. AB - Cytosolic phosphoenolpyruvate carboxykinase (GTP) (PEPCK) is a key glyceroneogenic enzyme in adipose tissue. The regulation of PEPCK gene expression by retinoic acid (RA) and dexamethasone (DEX) was studied in 3T3-F442A adipocytes maintained in a serum-free medium. RA induced whereas DEX reduced PEPCK mRNA steady-state level. RA stimulation was about 4-fold and DEX repression was of 80% in 4 hrs. In addition to reducing basal mRNA level, DEX was able to counteract RA induction in a dominant manner. The use of the glucocorticoid antagonist RU 38486 indicated that the DEX effect was mediated by the glucocorticoid receptor. Stable transfectants bearing the region of the PEPCK promoter from -2100 to +69 fused to the chloramphenicol acetyltransferase (CAT) gene (pPL1-CAT) were used to study PEPCK gene regulation in differentiated adipocytes. In such cells, RA stimulated CAT expression 3 to 5.5 fold. DEX had no effect on basal CAT activity whereas it inhibited the stimulation induced by RA. Thus, in adipocytes, the PEPCK gene regulatory region between -2100 and +69 bp mediates both stimulation by RA and repression by DEX of RA action. PMID- 7981625 TI - Effect of bradykinin on loss of density-dependent growth inhibition of normal rat kidney cells. AB - Normal rat kidney fibroblasts, density-arrested in the presence of epidermal growth factor (EGF), can be restimulated to proliferate in a synchronous way and acquire a transformed phenotype following treatment with additional growth factors like retinoic acid (RA) and transforming growth factor (TGF)-beta. It was found that bradykinin has a strong inhibitory effect on growth stimulation induced by these factors, an effect which cannot be mimicked by PGF2 alpha. The growth-inhibiting effect can be blocked by inhibitors of cyclo-oxygenase activity, indicating that the relevant second messenger is most likely a prostaglandin. Externally added PGJ2, at a concentration of 10 microM, can mimic the inhibitory effect of bradykinin on the loss of density-arrest induced by RA suggesting that PGJ2 is a possible candidate for being the bradykinin induced growth-inhibiting prostaglandin. PMID- 7981627 TI - Molecular genetics of blindness. PMID- 7981629 TI - Impact of gene targeting on medicine. PMID- 7981628 TI - Protein import deficiencies in human peroxisomal disorders. PMID- 7981630 TI - Genomic imprinting in humans. PMID- 7981631 TI - Superoxide dismutase, oxygen radical metabolism, and amyotrophic lateral sclerosis. PMID- 7981632 TI - Glutamate stimulates the phosphorylation of glial fibrillary acidic protein in slices of immature rat hippocampus via a metabotropic receptor. AB - Phosphorylation of the astrocyte cell marker glial fibrillary acidic protein (GFAP) in hippocampal slices from immature rats (10-16 days postnatal) was strongly stimulated by glutamate in the presence of Ca2+. This effect apparently occurred via a metabotropic receptor since the specific agonist of metabotropic glutamate receptors, 1S,3R-1-aminocyclopentane-1,3-dicarboxylic acid (1S,3R ACPD), stimulated GFAP phosphorylation by 173% whilst the mixed agonists, ibotenate and quisqualate, stimulated to a lesser extent. Ionotropic agonists were mainly ineffective. The action of 1S,3R-ACPD was blocked by L(+)-2-amino-3 phosphonopropionic acid (L-AP3) a specific antagonist of the metabotropic glutamate receptor coupled to the hydrolysis of phosphoinositides and was reduced by 70% by preincubation of the slices with pertussis toxin. In contrast to these results with immature animals glutamate had little or no effect on the phosphorylation of GFAP in hippocampal slices from adult rats. PMID- 7981633 TI - The depolarization-induced outflow of D-[3H]aspartate from rat brain slices is modulated by metabotropic glutamate receptors. AB - Rat brain slices were used to study the effects of different metabotropic glutamate receptor ligands on (i) the depolarization (30 mM KCl)-induced outflow of previously taken up D-[3H]aspartate; (ii) the inhibition of forskolin (30 microM)-induced cyclic AMP accumulation; and (iii) the hydrolysis of phosphoinositides. In addition, the localization of mRNAs coding for different metabotropic glutamate receptor subtypes was detected using in situ hybridization. (1S-3R)-1-Aminocyclopentane-1,3-dicarboxylic acid (30-300 microM), a non selective metabotropic glutamate receptor agonist, significantly increased the KCl-induced output of radioactivity from cortical slices, whereas it inhibited the output from striatal slices. Conversely, (1S,3S,4S) carboxycyclopropylglycine (0.1-1 microM), a relatively selective agonist of the mGluR2 metabotropic glutamate receptor subtype, had an inhibitory effect on the output of D-[3H]aspartate from both cortical and striatal slices and proved to be the most potent metabotropic glutamate receptor agonist in inhibiting cyclic AMP accumulation, but not in stimulating phosphoinositide hydrolysis. Since 2-amino-4 phosphonobutyrate (a mGluR4, mGluR6 and mGluR7 agonist) was not active in any of the assays tested, we hypothesized that the mGluR2 subtype could be involved in these events. Accordingly, mGluR2 mRNA expression was abundant in cortical neurons projecting to the striatum. Our experiments suggest that the stimulation of metabotropic glutamate receptors may either decrease or increase transmitter release depending on the subtype that prevails in the region under study. PMID- 7981634 TI - Is the heterologous expression of metabotropic glutamate receptors (mGluRs) an appropriate method to study the mGluR function? Experience with human embryonic kidney 293 cells transfected with mGluR1. AB - The cloning of metabotropic glutamate receptors (mgluRs) has initiated a new approach to the study of their function: the introduction of mGluR cDNA into cells that do not normally express mGluRs, thus allowing the heterologous receptor expression. We have transfected human embryonic kidney (HEK) 293 cells with the full length mGluR1a cDNA and with its truncated variant which encodes the receptor termed mGluR1T (a receptor lacking the long intracellular domain and similar to the splice variant mGluR1c). Transient transfection of HEK-293 cells with mGluR1a, but not the mGluR1T cDNA, resulted in a significant increase in inositol phosphate (IP) formation in absence of any mGluR agonists. This effect was completely dependent on the presence of extracellular calcium, and unlike the agonist-stimulated IP formation it was insensitive to pertussis toxin. The prolonged activation of IP formation might affect the cell physiology. In an attempt to obtain stably transfected cells, we transfected about 1.5 x 10(6) HEK 293 cells with the plasmid conveying the full-length mGluR1a cDNA and the neomycin-resistance gene. Only 12 clones survived the antibiotic selection, and only one of these 12 clones continued to divide. The size of mRNA from the clone was smaller than the full-length mGluR1a mRNA. The shortened mRNA, revealed in the clone, apparently encoded a functional mGluR that was sensitive to glutamate, but unlike the mGluR1a, it did not respond to 1S,3R-ACPD (1S,3R-aminocyclopentane 1,3-dicarboxylic acid). A prudent use of the heterologous cell transfection technique is necessary in studying the function and the pharmacology of mGluRs. PMID- 7981635 TI - Ethanol-induced alteration in activities of cerebral phosphatidylinositol 4,5 biphosphate-specific and cytosolic phospholipase C in the brain: analysis using NG 108-15 cells and brains from ethanol-inhaled mice. AB - Effect of long-term exposure to ethanol (EtOH) on the phosphatidylinositol 4,5 biphosphate (PIP2)-specific and cytosolic phospholipase C (PLC) activities in neuroblastoma x glioma hybrid (NG 108-15) cells and the brains from EtOH-inhaled mice were investigated. Long-term (2 days) exposure of NG 108-15 cells to EtOH induced significant decrease in PIP2-specific PLC activity dependent on concentration and duration of exposure, although the presence of EtOH in the enzyme assay system induced no alteration in PIP2-specific PLC activity. On the other hand, cytosolic PLC activity in NG 108-15 cells significantly increased by both the long-term exposure of the cells to EtOH and the addition of EtOH into the assay system. These changes in activities of both types of PLC in NG 108-15 cells observed after EtOH exposure recovered rapidly by the removal of EtOH. Moreover, the changes in activities of PIP2-specific and cytosolic PLC in the brain of EtOH-inhaled mice were similar to those found in NG 108-15 cells. These results indicate that EtOH inhibits the activity of PIP2-specific PLC and activates cytosolic PLC in the brain. These changes in cerebral PLC activities are suggested to involve in central action of EtOH and establishment of alcohol dependence. PMID- 7981636 TI - Chronic neonatal blockade of NMDA receptor does not affect developmental polyamine metabolism but results in altered response to the excitotoxic induction of ornithine decarboxylase. AB - Neonatal rats were subjected to chronic blockade of the N-methyl-D-aspartate (NMDA) receptor through daily systemic administration of increasing doses of the competitive antagonist CGP 39551 from postnatal days 1-22. Treatment did not result in any significant alteration of the levels of putrescine, spermidine and spermine or in the constitutively expressed activity of the key enzyme for polyamine biosynthesis, ornithine decarboxylase (ODC), as evaluated at 10 and 20 days of age. However, in 30-day-old rats significant differences were observed in the process of excitotoxic ODC induction in the olfactory cortex and the hippocampus of chronically-treated rats: the increase of ODC activity caused by systemic administration of kainic acid took place more rapidly but it was shorter and apparently reached a smaller peak in treated animals as compared to controls. This result, in conjunction with previous data on neurochemistry and locomotor activity of similarly treated rats, strengthens the suggestion that functional alterations of some brain circuits may be the consequence of the blockade of NMDA receptor during the critical neonatal period of brain maturation. PMID- 7981637 TI - Changes of cholinesterases in the blood and some tissues following administration of tacrin and its two derivatives to rats. AB - Tacrin, its 7-methoxy-(MEOTA) and 7-hydroxy-(HYOTA) derivatives were i.m. administered to rats in a dose of 1.2 x LD50 and acetylcholinesterase (blood, hippocampus, frontal cortex, basal ganglia, septum and diaphragm) or butyrylcholinesterase (liver) activities were detected. The inhibitory effect of the examined substances in vivo decreased in the following order: tacrin HYOTA > MEOTA. The marked inhibition of the enzymes studied following administration of all three compounds in the frontal cortex could suggest importance of this structure for action of these drugs. PMID- 7981638 TI - Quinolinic acid but not MK-801 protects the dopaminergic system from 1-methyl-4 phenyl-1,2,3,6-tetrahydropyridine-induced toxicity in goldfish retina. AB - The toxicity of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine, intravitreally injected in goldfish eye, involves interplexiform retinal neurons and depletes tyrosine hydroxylase immunoreactivity and dopamine levels. This induced neurotoxicity was prevented by the concomitant administration in non-toxic doses (10 micrograms) of quinolinic acid, an endogenous structural analogue of N-methyl D-aspartate with excitotoxic properties. Quinolinic acid is ineffective on the retinal degeneration induced by 1-methyl-4-phenylpyridinium ion. This fact suggests that quinolinic acid inhibits the MAO-B oxidation of 1-methyl-4-phenyl 1,2,3,6-tetrahydropyridine. MK-801, a noncompetitive antagonist of glutamate NMDA receptors, exerts partial protective effects on MPTP-induced delayed toxicity in mammals. In the goldfish eye, MK-801, injected in low concentration, and in conjunction with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine or 1-methyl-4 phenylpyridinium ion, did not prevent retinal neurodegeneration. Ten micrograms of MK-801 alone did not affect retinal neurons, while a higher concentration (20 micrograms) causes the chromatolysis of some photoreceptor nuclei. PMID- 7981639 TI - Autoradiographic comparison of [125I]LSD-labeled 5-HT2A receptor distribution in rat and guinea pig brain. AB - Although the density and distribution of 5-HT2A (5-hydroxytryptamine-2A) receptors is well established for rat brain, the 5-HT2A receptor distribution and density in guinea pig brain has not been extensively studied. In the present in vitro study, we have utilized 125I-lysergic acid diethylamide ([125I]LSD) to quantify and compare 5-HT2A receptor density in coronal sections of rat and guinea pig brain. Spiperone (1 microM) and sulpiride (1 microM) were used to displace [125I]LSD binding from 5-HT2A and D2 binding sites, respectively. Ligand binding was quantified by computer-aided image analysis densitometry (MCID). Similar to the rat, areas of highest specific 5-HT2A receptor binding (fmol/mg protein) in guinea pig brain included the claustrum and Layer 4 of the cerebral cortex. Significant binding was also found in remaining neocortical layers, islands of Calleja, caudate putamen, olfactory bulb, nucleus accumbens, and choroid plexus. While the rat brain exhibited a high level of specific binding in the tenia tecta and mammillary nuclei, little binding was observed in these regions in the guinea pig. In both rat and guinea pig, low specific binding was found in amygdaloid, thalamic, or cerebellar areas. These studies indicate a general similarity between 5-HT2A binding site distribution and relative density in guinea pig and rat brain but point to a few brain regions where significant differences exist. PMID- 7981640 TI - Release of [3H]GABA evoked by glutamate agonists from hippocampal slices: effects of dithiothreitol and glutathione. AB - The effects of dithiothreitol (DTT) and, reduced (GSH) and oxidized (GSSG), glutathione on the release of [3H]GABA evoked by glutamate and its agonists were studied in rat hippocampal slices. DTT had no effect on the basal release of [3H]GABA but it enhanced and prolonged the glutamate agonist-evoked release. This effect was abolished by (+)-5-methyl-10,11-dihydro-5H-dibenzo(a,d)cyclohept-5,10 imine hydrogen maleate (MK-801), a noncompetitive NMDA antagonist, and blocked by Mg2+ ions. It was only slightly attenuated by 6-cyano-7-nitroquinoxaline-2,3 dione (CNQX), a non-NMDA receptor antagonist, and not affected by L-(+)-2-amino-3 phosphonopropionate (L-AP3), a selective antagonist of the metabotropic glutamate receptor. The effect of DTT on the NMDA-evoked release of GABA was only slightly affected by extracellular Ca2+ but completely blocked by verapamil even in the absence of Ca2+. GSH and GSSG attenuated or abolished the effects of DTT on the agonist-induced release of [3H]GABA. The results imply that the enhanced and prolonged release of GABA evoked by the coexistence of DTT and excitatory amino acids and attenuated by endogenous GSH and GSSG is a consequence of sustained activation of the NMDA receptor-governed ionophores, which contain functional thiol groups. DTT, GSH and GSSG may regulate the redox state and accessibility of these groups. In addition to the influx of extracellular Ca2+, DTT mobilizes Ca2+ from intracellular pools distinct from those regulated by metabotropic glutamate receptors. PMID- 7981641 TI - Regional differences in the inhibition of L-glutamate and L-aspartate sodium dependent high affinity uptake systems in rat CNS synaptosomes by L-trans pyrrolidine-2,4-dicarboxylate, threo-3-hydroxy-D-aspartate and D-aspartate. AB - The sodium-dependent high affinity transport of L-[3H]glutamate and L [3H]aspartate into synaptosomal fractions prepared from three different regions was employed to investigate the inhibitors L-trans-pyrrolidine-2,4-dicarboxylate, threo-3-hydroxy-D-aspartate and D-aspartate. These substances showed regional heterogeneity as inhibitors of sodium-dependent high affinity uptake of L glutamate and L-aspartate. L-trans-Pyrrolidine-2,4-dicarboxylate was a more potent inhibitor of the uptake of L-glutamate than of L-aspartate in the cortex (IC50 8 microM vs L-glutamate and 13 microM vs L-aspartate) and cerebellum (IC50 4 microM v L-glutamate and 8 microM vs L-aspartate). threo-3-Hydroxy-D-aspartate was a more potent inhibitor of the uptake of L-glutamate than of L-aspartate in the cortex (IC50 9 microM vs L-glutamate and 13 microM vs L-aspartate) and hippocampus (IC50 6 microM v L-glutamate and 11 microM v L-aspartate). D Aspartate was a more potent inhibitor of the uptake of L-glutamate than of L aspartate only in the cortex (IC50 8 microM vs L-glutamate and 15 microM vs L aspartate). These results thus support other evidence that there is regional heterogeneity in sodium-dependent high affinity acidic amino acid uptake sites in the brain. PMID- 7981643 TI - [Order of intron positioning and distant correlations in nucleotide sequences]. PMID- 7981642 TI - Effect of physostigmine on relative acetylcholine output induced by systemic treatment with scopolamine in in vivo microdialysis of rat frontal cortex. AB - By means of an in vivo brain microdialysis, the effect of different concentrations of physostigmine on the acetylcholine level in the dialysate of rat frontal cortex was studied. Perfusion of the various degrees of physostigmine (eserine) concentration (10 nM-10 microM) into the cortex through the dialysis membrane increased the basal acetylcholine level in a dose-dependent manner. In the presence of 10 nM, 0.1 microM and 10 microM physostigmine in the perfusate, systemic treatment with scopolamine (0.5 mg/kg, i.p.) increased 200, 270 and 510%, respectively, the relative acetylcholine level in the dialysates in comparison with the corresponding basal levels, while in the absence of physostigmine the treatment increased it only 40%. From these results, it appears that perfusion of physostigmine at a variety of concentrations, changes not only the basal level of acetylcholine induced by the inhibition of acetylcholinesterase but also the relative acetylcholine output induced by systemic treatment with scopolamine. PMID- 7981644 TI - [A comparative study of the regenerative ability of skeletal muscles from adult rat and guinea pigs during laser therapy]. PMID- 7981645 TI - [Regulation of liberation and metabolism of dopamine in the dorsal striatum of free-living rats: the role of D2- and D3-dopamine autoreceptors]. PMID- 7981646 TI - [Radioactive pollution of the environment and biota on Novaia Zemlia due to nuclear weapons testing]. PMID- 7981647 TI - [Experience in ecological classification of parasitoses by source of invasion]. PMID- 7981649 TI - Ageing erythrocytes and alloxan diabetes: II. Role of thyroxine in reversing diabetic state. AB - The erythrocytes from control (C), diabetic (D) and thyroxine-treated diabetic (D+T4) rats were separated into three ageing groups (TAG) like light dense (young cells), intermediate-dense (middle-aged cells) and heavy-dense (old aged cells). Thyroxine reversed the diabetic defense enzymes to normal values like catalase in young cells, glutathione-s-transferase in middle-aged and old cells and levels of GSH in middle-aged cells. Thyroxine also increased the levels of GSSG in TAG whereas the levels of GSH increased in young cells, and decreased in old cells. The percentage of glycosylated haemoglobin did not return to normal levels by thyroxine in diabetic animals. Thyroxine may be playing the dual role in increasing the sulfhydryl levels and also inactivating enzymes in ageing erythrocytes of diabetic animals. PMID- 7981650 TI - Protective effect of exogenous coenzyme Q against damage by adriamycin in perfused rat liver. AB - We have investigated the effect of rat liver perfusion with adriamycin on mitochondrial activities. Although the perfusion treatment per se induces some decline of respiratory activities, adriamycin strongly potentiates this effect; moreover the coenzyme Q9 content of the mitochondrial membrane is significantly lowered by the antibiotic. Coaddition of coenzyme Q10 in the perfusate significantly protects the mitochondria, not only from loss of respiratory activities but also of the endogenous CoQ9 content. Exogenous CoQ10 fails to enhance respiratory activities in control rats, not treated with adriamycin, even though CoQ concentration has been proven not to be kinetically saturating in the respiratory chain under physiological conditions. Thus, the beneficial effect of CoQ10 in the perfusate does not appear to be the result of its role in the respiratory chain but is a consequence of its antioxidant action. PMID- 7981648 TI - Diagnostic and prognostic role of plasma and urinary sialic acid in human carcinoma of uterine cervix. AB - In different stages of carcinoma of uterine cervix, the plasma total sialic acid (TSA), lipid bound sialic acid (LSA) and urinary sialic acid levels were studied before and after radiation treatment. Glycocomponents of glycoproteins were found to be increased progressively as the disease advances. The increased levels of glycocomponents were found to be decreased to near normal levels after radiotherapy. This may be a better indicator of the disease in conjunction with the studies of cervical smear rather than the latter alone. PMID- 7981651 TI - Transforming growth factor--alpha stimulates chemotaxis of osteoblasts and osteoblast-like cells in vitro. AB - Homeostatic turnover of bone is believed to be regulated in part by growth factors present in the surrounding environment. The first step during the bone formation process is the recruitment of osteoblasts from the surrounding intact bone to the resorption site. In this study, the effects of TGF-alpha on osteoblast chemotaxis was investigated. Cultures of rat osteoblasts and human osteoblast-like cells were examined for chemotaxis in response to increasing concentrations of TGF-alpha utilizing a modified Boyden Chamber technique. TGF alpha stimulated a dose-dependent increase in chemotaxis by both cell populations. These results indicate that TGF-alpha may be playing an important role in the early stages of bone matrix regeneration by stimulating osteoblast chemotaxis. PMID- 7981652 TI - Molecular cloning of gyrA and gyrB genes of Mycobacterium tuberculosis: analysis of nucleotide sequence. AB - We have recently reported the cloning of gyrA and gyrB genes from Mycobacterium tuberculosis H37Ra [Curr. Science, (1994) 66, 664-667]. Here, we present the complete nucleotide sequence of gyrB gene from M. tuberculosis H37Ra along with the flanking regions. The gyrA gene has been located 34 nucleotides downstream of gyrB and has been partially sequenced; both the genes seem to be transcribed from the promoter elements located upstream of gyrB coding sequence. The gyrB gene encodes a polypeptide of 714 amino acids. The deduced amino acid sequences of gyrB and a part of gyrA show extensive homology to the corresponding genes from other bacterial species. The DNA gyrase of M. tuberculosis could be utilised to develop new line of antitubercular drugs. PMID- 7981653 TI - Purification of tropomyosin from bovine adrenal medulla and its inhibitory effect on the actin severing activity of adseverin (adrenal medulla 74 kDa actin severing protein). AB - Tropomyosin was purified from a gelation product produced in the crude extract of bovine adrenal medulla using several column chromatographies mixed with a boiling treatment. Purified tropomyosin was a mixture of major isoforms with low molecular weights and minor isoforms of high molecular weights. Purified tropomyosin showed a dose-dependent protective effect on actin filaments against the severing activity of adseverin derived from adrenal medulla, suggesting its important role in the regulation of cell shape and structure in vivo. PMID- 7981654 TI - alpha-Lipoic acid protects against hemolysis of human erythrocytes induced by peroxyl radicals. AB - The azo initiator of peroxyl radicals 2,2'-azobis (2-amidinopropane) dihydrochloride (AAPH) induces oxidative hemolysis in human erythrocytes and subsequent hemoglobin oxidation. Using the degree of hemolysis versus time as an indication of the oxidative damage it was found that i) both reduced and oxidized alpha-lipoic acid protected against oxidative damage; ii) simultaneous treatment of erythrocytes with ascorbate and dihydrolipoate or alpha-lipoate has a synergistic tendency to protect cells against hemolysis; iii) glutathione in combination with dihydrolipoic acid or alpha-lipoic acid has an additive effect on hemolysis protection. The spin trapping reagent 5,5-dimethyl-1-pyrroline N oxide (DMPO) formed an adduct with the peroxyl/alkoxyl radicals produced by thermal decomposition of AAPH in the presence of oxygen. The formation of this adduct was prevented by reduced or oxidized lipoic acid, reduced glutathione or ascorbate. It is concluded that AAPH-peroxyl radicals progressively damage the cells and the released hemoglobin is subsequently oxidized to methemoglobin which might further enhance the oxidative damage. The protective effect of antioxidants is exerted outside the cells by directly scavenging AAPH-alkoxyl radicals. PMID- 7981655 TI - The effect of chronic tumour necrosis factor-alpha treatment on urinary nitrogen excretion in the rat. AB - Chronic tumour necrosis factor-alpha (TNF) treatment of rats for 4 days resulted in transient decreases in food intake and body weight, 24 h after the beginning of the cytokine treatment. Treatment with the cytokine resulted in a large increase in circulating urea concentrations. The urinary excretion of urea and creatinine is increased following TNF treatment. 3-methylhistidine, an indicator of contractile protein breakdown, is also elevated in the urine of the animals treated with the cytokine. From previous observations (1) and the data presented here, it is suggested that TNF enhanced muscle catabolism even in experimental situations were body weight loss was not apparent. PMID- 7981656 TI - Differential expression of stress proteins in virulent and attenuated promastigotes of Leishmania donovani. AB - Induction of stress proteins in response to heat shock and/or pH shock was compared in virulent and attenuated promastigotes of Leishmania donovani. The virulent strain showed increased expression of heat shock proteins (HSPs) of 110, 83, 70, 65, 40 and 12 kDa on heat shock (37 degrees C), while the attenuated form showed increased expression of HSPs 83, 70 and 65 only. In response to a low pH (4.5), the virulent promastigotes showed a significantly greater increase in the relative synthesis of HSP83 and HSP 70 as compared to the attenuated promastigotes. A combination of heat shock and pH shock led to an increase in the synthesis of HSP 83 and HSP 70 in the virulent parasites, while the attenuated strain showed marked increase in HSP 70 only. These results point to an important role of HSPs in the differentiation and/or virulence of L. donovani. PMID- 7981657 TI - Significant association of lipid peroxidation products with high density lipoproteins. AB - In this study the role of high density lipoproteins in lipoprotein peroxidation process was investigated. Under basal conditions, HDL isolated from human plasma or from total lipoprotein fraction (density > 1.21) using precipitation technique carried nearly 35-40% of the total plasma fatty acid peroxidation product (measured as malonaldehyde, MDA). HDL associated MDA was reduced to < 20% when HDL was isolated by ultracentrifugation from plasma treated with Cu++. Under these conditions, 45% of the cholesterol peroxidation products (oxysterols) were associated with HDL. HDL isolated from Cu++ treated plasma significantly lost its ability to inhibit LDL peroxidation. These results suggest that HDL plays an important role in lipid peroxidation a) by carrying significant amounts of cholesterol and lipid peroxidation products, and b) its ability to inhibit LDL oxidation is compromised when HDL itself is oxidized. PMID- 7981659 TI - Ca(2+)-dependent and independent interactions of calretinin with hydrophobic resins. AB - The ability of rat calretinin to bind to hydrophobic resins in a Ca(2+)-dependent manner was examined. Both native calretinin present in cerebellum extract and purified recombinant calretinin bound similarly to hydrophobic resins such as phenyl-, hexyl-, octyl-, and W7-agarose. Hydrophobic interactions of calretinin were partially Ca(2+)-dependent since 1/3 of bound protein was released from the resins by EGTA under varied conditions. Some calretinin tryptic fragments bound to octyl-agarose in a manner similar to uncleaved calretinin, while others bound to the resin in a Ca(2+)-independent manner. These and other results suggest that calretinin has several hydrophobic regions of varied strength and sensitivity to Ca2+. It is proposed that the local changes in hydrophobicity induced by Ca2+ binding might be relevant for calretinin functions. PMID- 7981658 TI - In vitro effects of hydroxystearic acid on the proliferation of HT29 and I407 cells. AB - The in vitro effects of hydroxystearic acid on the proliferation of human colon carcinoma cells (HT29) and human embryonic intestine cells (I407) were examined and compared to previous results obtained in murine C108 lung carcinoma cells. The cells were cultured in the presence, or in the absence, of hydroxystearic acid and tested for cell proliferation and viability; the distribution of cells in the cell cycle was evaluated by flow cytometry. Results show that hydroxystearic acid is also an inhibitor of human cell proliferation, and not only of murine C108 cells. Differently from C108 cells, which upon treatment with hydroxystearic acid accumulate in G2-M phases, hydroxystearic acid-treated HT29 cells increase significantly in numbers in G0-G1; I407, embryonic cells used as a control, when treated show only a slight increase in G0-G1. PMID- 7981660 TI - A study on the mechanism of polymerisation of Bacillus brevis flagellin. AB - Optical properties of intact flagellin and of modified-on-tyrosine flagellin incapable of self-assembly have been studied by the circular dichroism (CD) method. The CD spectra of both flagellins do not change and virtually coincide within the pH range from 2.9 to 10.0. In the presence of polyethylene glycol (PEG) and ammonium sulfate which accelerate flagellin polymerization, the character of the CD spectra changes and depends on pH. The increase in the PEG content to 20% and that in the ammonium sulfate content to 1 M over the pH range from 4.3 to 10.0 results in a significant rise of the molar ellipticity at 222 nm ([theta]222) of both flagellins. However, [theta]222 does not reach values typical for bacterial flagella. The results obtained are discussed with respect to conformational changes in the flagellin molecule during polymerization. PMID- 7981661 TI - Lead perturbs calmodulin dependent cyclic AMP metabolism in rat central nervous system. AB - The effect of chronic lead exposure on calmodulin regulated cAMP metabolism in rat brain, was investigated in the present study. Lead was observed to activate calmodulin, both in vivo and in vitro and thus mimic calcium in its actions. Lead had a biphasic effect on the activity of calmodulin dependent cAMP phosphodiesterase, i.e. at lower concentrations lead activated the enzyme and at higher concentrations inhibited it. In vivo lead exposure resulted in stimulation of the soluble cAMP phosphodiesterase activity. Adenylyl cyclase activity was significantly inhibited in calmodulin rich and depleted synaptic plasma membranes following in vitro and in vivo lead exposure. The activity of forskolin and dopamine stimulated adenylyl cyclase was also similarly inhibited by lead ions. The results were further substantiated by the decreased intracellular levels of cAMP in brain of lead treated animals. Our observations suggest, cAMP messenger system to be a target candidate in lead neurotoxicity. PMID- 7981662 TI - Inhibition of prophenoloxidase-activating enzyme from Bombyx mori by endogenous chymotrypsin inhibitors. AB - Inhibitory activities for the activation of prophenoloxidase with its activating enzyme were detected in the gel-filtration fractions of hemolymph from Bombyx mori. The fractions with the highest activity contained chymotrypsin inhibitors; CI-13a, 13b, and 13c. They inhibited the activation of prophenoloxidase. The activating enzyme affected a synthetic substrate for trypsin, Boc-Gln-Ala-Arg MCA: Km = 0.62 mM. CI-13c partially suppressed the peptidase activity. PMID- 7981663 TI - Circular dichroism studies of acid proteinases from Aspergillus niger and Aspergillus awamori. AB - Acid proteinases produced by strains of Aspergillus niger and Aspergillus awamori were isolated by means of ethanol precipitation, gel filtration and anion exchange high resolution chromatography. In each case, the purified proteinase showed a single band in polyacrylamide gel electrophoresis. Their molecular weights were almost identical (approx. 45,000). However, the proteinase from Aspergillus awamori contained 16% of neutral hexoses while the other enzyme (Aspergillus niger) showed negligible amounts of these carbohydrates. Both enzymes displayed circular dichroism spectra that share a number of features with that of penicillopepsin. This suggests that proteinases from Aspergilli possess the structural folding pattern typical of aspartic proteinases. Proteolytic activity pH optima were different, thus distinguishing one enzyme from another. This variation seems to be related to the particular resistance of the proteinases to acid denaturation, as indicated by changes in their circular dichroism spectra when the pH is decreased. PMID- 7981664 TI - Origin of the N-1, C-2 and C-2' atoms of the pyrimidine moiety of thiamin in Saccharomyces cerevisiae. AB - The precursor of the pyrimidine moiety of thiamin in S. cerevisiae was studied. The tracers [15N]- and [2'-13C]-pyridoxine were chemically synthesized, and incorporated efficiently into the pyrimidine. The mass fragmentation pattern showed that the nitrogen atom of pyridoxine was incorporated into the N-1 of the pyrimidine. In addition, the C-2' atom of pyridoxine was incorporated into the C 2' atom of the pyrimidine. These results and the structural resemblance between the pyrimidine and pyridoxine revealed that the C-2, C-2' and N-1 unit of the pyrimidine are derived from the C-2, C-2' and N-1 unit of pyridoxine. PMID- 7981665 TI - Characterization of urokinase-type plasminogen activator of rat decidual tissue. AB - Urokinase-type plasminogen activator (uPA) from artificially induced decidual tissue of rat has been purified to homogeneity employing chromatographic techniques and the final preparation has a specific activity of 12,084 I.U./mg. The purified preparation resolves into a single band following SDS-PAGE and has an apparent molecular weight of 45 kDa. HPLC of the purified fraction also yields a single peak at 45 kDa. Decidual uPA is immunogenic in rabbit and a monospecific antiserum raised against it does not cross react with human melanoma tPA or rat Yoshida sarcoma tPA but elicits a precipitin reaction with human uPA and extracts of rat placenta and kidney. The enzyme has a pH optimum of 7.5, a kM of 1.0 microM, is heat stable upto ten minutes at 42 degrees C and inhibited by anti-uPA IgG. PMID- 7981666 TI - Activity staining of halophilic enzymes: substitution of salt with a zwitterion in non-denaturing electrophoresis. AB - Several NAD(P)(+)-dependent dehydrogenases were partially purified from Halobacterium halobium. When salt (2M (NH4)2SO4) was replaced with glycine betaine (4M or 6M), the zwitterion stabilised activity less completely than the salt. Nevertheless most of the enzyme activity still remained after 90h, e.g. 70% for malate dehydrogenase. This level of stabilisation permitted non-denaturing gel electrophoresis in 4M betaine after dialysis to replace salt. Coomassie Blue staining showed good separation of the proteins, and activity staining, hitherto impossible for halophilic enzymes, readily identified the individual dehydrogenase bands. Transfer of activity-stained gels to Coomassie staining solution halted background formazan staining and showed up activity and other protein bands in contrasting colours. PMID- 7981667 TI - Density gradient separation of L-asparaginase-loaded human erythrocytes. AB - L-Asparaginase has been encapsulated in human red blood cells using a hypotonic dialysis process. Erythrocytes loaded with L-Asparaginase were separated into eight fractions using a discontinuous Percoll density gradient. A minor cell subpopulation of low density cells and a major subpopulation of denser erythrocytes was obtained after hypotonic dialysis treatment, in both the absence or presence of L-Asparaginase. The encapsulated L-Asparaginase activity per resealed erythrocyte was higher in low-density cells and decreased progressively with increasing in cellular density. PMID- 7981668 TI - A complete cDNA sequence for core I protein subunit of human ubiquinol-cytochrome c reductase. PMID- 7981669 TI - Factor VIII gene inversions causing severe hemophilia A originate almost exclusively in male germ cells. AB - The factor VIII gene, which is defective in hemophilia A, is located in the last megabase of the long arm of the X chromosome. Inversions due to intrachromosomal homologous recombination between mispaired copies of gene A located within intron 22 of the gene and about 500 kb telomeric to it account for nearly half of all cases of severe hemophilia A. We hypothesized that pairing of Xq with its homolog inhibits the inversion process, and that, therefore, the event originates predominantly in male germ cells. In all 20 informative cases in which the inversion originated in a maternal grandparent, DNA polymorphism analysis determined that it occurred in the male germline. In addition, all but one of 50 mothers of sporadic cases due to an inversion were carriers. Thus, these data support the hypothesis and indicate that factor VIII gene inversions leading to severe hemophilia A occur almost exclusively in male germ cells. PMID- 7981670 TI - Cloning and characterization of the human choroideremia gene. AB - Positional cloning has previously resulted in the identification of a gene which is disrupted by deletions in patients with the classic choroideremia (CHM) phenotype. More subtle mutations had been identified in 4 exons of the 3' portion but not elsewhere in the CHM gene. We have now isolated and characterized the complete open reading frame of the CHM gene and determined its exon-intron structure. The CHM gene encodes a protein of 653 amino acids, which is highly homologous to the mouse and rat CHM proteins, and, to a slightly lesser extent, to the human CHM-like (CHML) protein. The open reading frame (ORF) of the human CHM gene consists of 15 exons, spanning at least 150 kb of Xq21.2, and it is possible that there is an additional exon corresponding to the 5' non-coding region of the gene. Cloning of the 5' end of the CHM gene and the elucidation of its intron-exon structure enabled us to localize the X-chromosomal breakpoint in a CHM female with an X;7 translocation between exons 3 and 4. PMID- 7981671 TI - Mutation spectrum in the CHM gene of Danish and Swedish choroideremia patients. AB - The recent isolation of the complete open reading frame of the choroideremia (CHM) gene and the characterization of the exon-intron boundaries has paved the way to mutation detection in patients with classical choroideremia. We have performed mutation screening in patients from 15 Danish and Swedish families by using Southern blot hybridization and the polymerase chain reaction single-strand conformation polymorphism (PCR-SSCP) technique. Causative mutations in the CHM gene were detected in at least 12 families, indicating that a substantial part of the mutations can be identified by this approach. In four of these families deletions of different sizes were found. Thus, in one patient, the deletion resulted in the absence of only one exon, while in another the deletion comprised the entire CHM gene. Mapping of the deletion endpoints in these four patients and in another 11 male patients with sizeable deletions enabled us to construct a very detailed map of intervals 2 and 3 of Xq21. In the remaining 11 Danish and Swedish families at least 8 causative mutations were found by PCR-SSCP analysis and direct sequencing. Interestingly, all CHM gene mutations detected thus far in choroideremia patients give rise to the introduction of a premature stop codon. PMID- 7981672 TI - Absence of the XIST gene from late-replicating isodicentric X chromosomes in leukaemia. AB - The mechanism of X-inactivation in man is thought to involve a specific cis acting locus within the X-inactivation centre at Xq13 (1,2). The XIST gene (X inactive specific transcript) at Xq13 is ubiquitously expressed only from the inactive X and as such may be involved in or influenced by the X-inactivation process (3,4). We have localised the breakpoints on two acquired isodicentric X chromosomes associated with leukaemia to a 450 kilobase region of DNA within Xq13, which result in deletion of the XIST gene. We have demonstrated that these chromosomes remain inactive and that there is no evidence of XIST expression from the remaining intact X chromosomes. The data suggest that XIST is not required for the maintenance of X-inactivation on these somatically rearranged X chromosomes. PMID- 7981674 TI - PAX3 gene structure and mutations: close analogies between Waardenburg syndrome and the Splotch mouse. AB - The human PAX3 gene contains a paired box and a paired-type homeobox, and is believed to play a role in pattern formation in the embryo. We describe the exon intron structure of the homeobox-containing part of PAX3, complementing earlier descriptions of the 5' part of the gene. Mutations in PAX3 have been described in patients with Type 1 Waardenburg syndrome, who have hearing loss and pigmentary abnormalities, while Splotch mice have mutations in the homologous mouse Pax-3 gene. We describe a series of patients who have previously unidentified PAX3 mutations. These include a chromosomal deletion, a splice-site mutation and an amino acid substitution which closely correspond to the molecular changes seen in the Splotch-retarded, Splotch and Splotch-delayed mouse mutants respectively. These mutations confirm that Waardenburg syndrome is produced by gene dosage effects and show that the phenotypic differences between Splotch mice and humans with Waardenburg syndrome are caused by differences in genetic background rather than different primary effects of the mutations. PMID- 7981673 TI - Isolation of new genes in distal Xq28: transcriptional map and identification of a human homologue of the ARD1 N-acetyl transferase of Saccharomyces cerevisiae. AB - In this paper, we describe the physical and transcriptional organization of a region of 140 kb in Xq28, 5' to the L1CAM gene. By isolation and mapping of CpG islands to the physical map of the region, isolation of cDNAs, determination of partial nucleotide sequences and study of the pattern of expression and of the orientation of the transcripts identified we have established a transcriptional map of this region. In this map, previously identified genes (L1CAM, V2R, HCF1 and RnBP) have been positioned as well as 3 new genes. All genes in the region are rather small, ranging in size from 2 to 30 kb, and very close to one another. With the exception of the V2R gene, they are housekeeping, have a CpG island at their 5' end and the same orientation of transcription. This kind of organization is consistent with the one previously described for the more distal portion of Xq28, between the Color Vision (CV) and the G6PD genes and indicates that genes with housekeeping and tissue specific pattern of expression are interspersed in the genome but they are probably found in different 'transcriptional domains'. Among the new genes, TE2 demonstrated 40% identity with the protein N-acetyl transferase ARD1 of S. cerevisiae: TE2 may be the human homologue of the S. cerevisiae gene. PMID- 7981675 TI - Alternative transcripts in the mouse neurofibromatosis type 2 (NF2) gene are conserved and code for schwannomins with distinct C-terminal domains. AB - Mutations in the neurofibromatosis type 2 (NF2) gene predispose individuals to the development of nervous system tumors and ocular abnormalities. The NF2 gene product, schwannomin, is a member of a superfamily of proteins thought to link cytoskeletal elements to cell membrane components. These proteins share significant homologies in the N-terminal and alpha-helical domains, but diverge in the C-terminus. During our efforts to characterize mouse NF2 transcripts, we identified four different transcripts by cDNA analysis and reverse-transcribed PCR that contained different sequences in the 3' end of the coding sequences. In human cell lines three isoforms encoding two distinct schwannomins were detected. The mouse and human transcripts containing 61 and 60 bp inserts, respectively, have not been previously described. The isoforms encode schwannomins with significantly altered C-termini and were expressed at different relative levels in adult mouse tissues and during mouse embryogenesis. These results suggest that schwannomin isoforms have distinct functional roles and predict the existence of human mutations involving the C-terminus of schwannomin. PMID- 7981676 TI - A de novo 13 nt deletion, a newly identified C647W missense mutation and a deletion of exon 18 in infantile onset glycogen storage disease type II (GSDII). AB - We identified the presumably rare event of de novo mutation in an autosomal recessive disorder, glycogen storage disease type II (GSDII). GSDII results from inherited deficiency of acid alpha-glucosidase (acid maltase) and both the expressed and structural gene (designated GAA) have been isolated. The mutation was a deletion of 13 nt of coding sequence (delta nt 1456-1468) on the paternally derived allele of the proband. The delta nt 1456-1468 results in a reading frameshift and a premature termination signal upstream of the enzyme catalytic site. Paternity was confirmed by presence of two downstream, uncommon amino acid substitutions (E689K, W746C) in both proband and father and by comparison of nine short tandem repeats. The maternal allele carried a newly identified deleterious C647W missense mutation in a highly conserved area of the protein. The C647W mutation was also found in a second unrelated proband, heteroallelic with a deletion extending from IVS17 to IVS18. PMID- 7981677 TI - Physical linkage of expressed sequence tags (ESTs) to polymorphic markers on the X chromosome. AB - Expressed sequence tags (ESTs) can in principle serve as specialized sequence tagged sites (STSs) to assemble a functional map of the human genome. The strategy of physically linking ESTs to the nearest genetic linkage markers should provide specific candidate genes for the X-linked diseases associated with these markers or loci. Therefore, 19 ESTs assigned to the X chromosome in the Genome Database (GDB) were analyzed. Eighteen were confirmed to be X-specific and were localized to regions of the X chromosome using a panel of somatic cell hybrids. Localization was then refined by positioning them on yeast artificial chromosome (YAC)-based maps. Seventeen ESTs identified cognate YACs by PCR screening and 12 of the ESTs have been assembled in YAC contigs containing polymorphic and other X chromosomal markers. Two of them also produced syntenically equivalent products in mouse. Thus localizing ESTs relative to polymorphic markers will help to assemble an integrated physical and transcriptional map of the chromosome and provide candidates for disease-gene searches. PMID- 7981678 TI - Identical genotypes in siblings with different homocystinuric phenotypes: identification of three mutations in cystathionine beta-synthase using an improved bacterial expression system. AB - We determined the molecular basis of cystathionine beta-synthase (CBS) deficiency in three siblings with pyridoxine responsive homocystinuria using a significantly improved mutation screening method in bacteria. The phenotypic expression of the siblings differed even though their CBS genotypes were identical. The paternal allele contained a linked pair of mutations, C233G and G306C, corresponding to P78R and K102N in the polypeptide chain. Together, these inactivated the enzyme; however, expressed separately, they reduced activity by about one half. The single maternal mutation G715A (E239K) effectively abolished CBS activity. Subunits of CBS were absent from patient fibroblast extracts; however, E. coli, transformed with plasmids containing patient CBS cDNA, expressed the subunits, although in reduced amounts. The mother, an obligate heterozygote, was free from all signs of homocystinuria; nonetheless, extracts of her fibroblasts were devoid of CBS protein and activity. We conclude that fibroblast levels of CBS are only partially effective as prognosticators of disease severity and that it is important to test the in vivo response to vitamin B6 in all cases of homocystinuria, including those in which the mutations lead to the absence of the enzyme in cultured fibroblasts. PMID- 7981679 TI - Characterisation of inherited and sporadic mutations in neurofibromatosis type-1. AB - Neurofibromatosis type-1 (NF-1) is an autosomal dominant disorder, caused by mutations in the NF-1 gene. Mutation analysis in the NF-1 gene is complicated by the large size of the gene, the high mutation rate, and the presence of pseudogenes. By means of the polymerase chain reaction, we have amplified 70% of the NF-1 coding sequence using reverse transcribed mRNA and genomic DNA from 25 unrelated Scottish Caucasian patients. We have used chemical mismatch cleavage analysis and direct sequencing of asymmetrically amplifed PCR products to characterise mutations within the NF-1 gene. Using the above strategy, we detected 10 novel mutations and an intragenic polymorphism with a heterozygosity of approximately 47% in the Scottish population. Of the 10 mutations, 7 are potentially disease causing. They include splice site errors responsible for exon skipping (1721 + 3A to G) and (5749 + 2T to G), small insertions (7485insGG) and (6519insG), a nonsense mutation (R2496X), and missense and silent mutations (G1166D, K1419R, G1404G, S1311S, N1776N). A correlation of the phenotype with the genotype is presented. Thus, in this study we have identified a heterogeneous group of germline mutations, the majority of which are predicted to cause disruption of the protein product, neurofibromin. This approach has therefore proved to be useful for the detection of mutations in the gene for neurofibromatosis type-1, and can be applied to detection of molecular pathologies in general. PMID- 7981680 TI - Mono- and bi-allelic expression of insulin-like growth factor II gene in human muscle tumors. AB - Insulin-like growth factor II (IGF-II) is a mitogen for many cell types and an important modulator of muscle growth and differentiation. IGF-II gene is prevalently expressed during prenatal development and its gene activity is regulated by genomic imprinting, in that the allele inherited from the father is active and the allele inherited from the mother is inactive in most normal tissues. IGF-II expression is activated in several types of human neoplasms and an alteration of IGF-II imprinting has been described in Beckwith-Wiedemann syndrome and Wilms' tumor. Here we show that monoallelic expression of IGF-II gene is conserved in normal adult muscle tissue whereas two or more copies of active IGF-II alleles, arising by either relaxation of imprinting or duplication of the active allele, are found in 9 out of 11 (82%) rhabdomyosarcomas retaining heterozygosity at 11p15, regardless of the histological subtype. Since IGF-II has been indicated as an autocrine growth factor for rhabdomyosarcoma cells, these findings strongly suggest that acquisition of a double dosage of active IGF-II gene is an important step for the initiation or progression of rhabdomyosarcoma tumorigenesis. Among different types of muscle tumors, relaxation of imprinting seems to arise prevalently in rhabdomyosarcomas, since we have detected only one case of partial reactivation of the maternal IGF-II allele out of 7 leiomyosarcomas tested. PMID- 7981681 TI - Proof of a non-functional muscle chloride channel in recessive myotonia congenita (Becker) by detection of a 4 base pair deletion. AB - Recessive myotonia congenita (Becker) is genetically linked to HUMCLC, the gene encoding the muscular chloride channel, localized on chromosome 7q35. Three point mutations have so far been reported in HUMCLC, one causing recessive Becker-type myotonia, the others causing the clinically similar Thomsen-type myotonia, which is inherited as a dominant trait. We report a homozygous patient having a 4 base pair deletion in HUMCLC that shifts the reading frame and causes early stop codons, thus destroying the gene's coding potential for several membrane-spanning domains. In addition, we report a patient homozygous for a novel point mutation located at the extracellular side of the first membrane-spanning domain that causes removal of a negative charge (aspartic acid-136-glycine). Both mutations lead to the recessive type of myotonia congenita. Since the patient having the deletion presents less severe clinical myotonia than the patient carrying the missense mutation, it seems that the absence or truncation of the channel protein may disturb muscle fibre function less than the substitution of a single amino acid. PMID- 7981682 TI - Polymorphism analysis of the huntingtin gene in Italian families affected with Huntington disease. AB - Two sources of variation in the huntingtin gene, the length of the CCG-rich segment downstream to the (CAG)n stretch undergoing expansion in Huntington disease (HD) and the deletion of 3 bp at codon positions 2642-2645 (delta 2642), were analysed on the normal and HD chromosomes of 80 Italian families affected with HD. No instances of meiotic instability of the CCG-rich segment were detected. A strong linkage disequilibrium was found between the HD mutation and alleles at both polymorphic regions: CCG-rich length alleles different from 176 bp are underrepresented while delta 2642 is overrepresented on HD chromosomes. The presence of such alleles on HD chromosomes does not affect age at onset of the disease. Normal chromosomes displayed a non-random association, shorter (CAG)n segments being preferentially followed by longer CCG-rich segments. Finally, the finding, among normal subjects, of carriers of variants on both chromosomes denotes that variation at either of the two polymorphisms does not impair the function of the huntingtin gene product. PMID- 7981683 TI - A novel transmembrane transporter encoded by the XPCT gene in Xq13.2. AB - To study the regulation and chromosomal basis of X chromosome inactivation, we have physically characterized the region in Xq13.2 known to contain the X inactivation center (XIC), a locus required in cis for inactivation to occur. Here, we report a novel gene isolated by positional cloning in this region. The gene (previously identified as DXS128E) encodes a predicted 67 kDa protein containing twelve hydrophobic transmembrane domains, characteristic of a family of transporter proteins. Presence of an N-terminal PEST domain, consisting mainly of proline/glutamic acid repeats, suggests that the protein may be rapidly or conditionally degraded. We designate this gene XPCT for X-linked PEST-containing transporter. Expression studies suggest that XPCT is subject to X chromosome inactivation, being expressed only from the active X, despite mapping within 600 kb of the XIST gene which is expressed exclusively from the inactive X. Thus, a chromosomal switch in inactivation pattern occurs between these two genes on the X chromosome. PMID- 7981685 TI - X-linked mixed deafness (DFN3): cloning and characterization of the critical region allows the identification of novel microdeletions. AB - We have found that the microsatellite marker AFM207zg5 (DXS995) maps to all previously described deletions which are associated with X-linked mixed deafness (DFN3) with or without choroideremia and mental retardation. Employing this marker and pHU16 (DXS26) we have identified two partially overlapping yeast artificial chromosome clones which were used to construct a complete 850 kb cosmid contig. Cosmids from this contig have been tested by Southern blot analysis on DNA from 16 unrelated males with X-linked deafness. Two novel microdeletions were detected in patients which exhibit the characteristic DFN3 phenotype. Both deletions are completely contained within one of the known DFN3 deletions, but one of them does not overlap with two previously described deletions in patients with contiguous gene syndromes consisting of DFN3, choroideremia, and mental retardation. Assuming that only a single gene is involved, this suggests that the DFN3 gene spans a chromosomal region of at least 400 kb. PMID- 7981684 TI - Localization of the gene whose mutations underlie Hailey-Hailey disease to chromosome 3q. AB - Hailey-Hailey disease (familial benign chronic pemphigus) is an autosomal dominant skin disease characterized by impaired keratinocyte cohesion and consequent blister formation. In the present study we have used linkage analysis to map the gene for this disease to a region of chromosome 3q between D3S1589 and D3S1316. The maximum combined two point lod score in four families studied was 14.60 at theta = 0 at the D3S1290 microsatellite repeat. These findings suggest the presence of a gene not previously known to be involved in keratinocyte cohesion at this site. PMID- 7981686 TI - A YAC-based binning strategy facilitating the rapid assembly of cosmid contigs: 1.6 Mb of overlapping cosmids in Xp22. AB - We have applied a yeast artificial chromosome (YAC)-based cosmid isolation and binning strategy to convert a YAC contig in Xp22 into 1.6 Mb of overlapping cosmids. This strategy is based on the screening of a high-density arrayed X chromosome-specific cosmid library with large YAC-derived restriction fragments and entire YAC probes. Cosmids selected in this way were gridded on dot blots and further mapped into bins defined by the overlap intervals of the YACs and YAC fragments. This rapid binning of cosmids simplified the subsequent assembly of cosmid contigs by restriction fingerprint hybridization. In total, we identified 139 cosmids spanning the entire 1.6 Mb region with a minimal overlap set of 53 clones. These cosmids were assigned to 17 bins and 9 contigs. One of the contigs is 665 kb in length and is one of the largest uninterrupted cosmid contigs in humans reported to date. The gaps between the contigs are minor and, together, they represent less than 7% of the region covered. Two previously identified genes are contained in these cosmids, the gene for amelogenin (AMG) and the recently isolated putative chloride channel gene CICN4. In addition, two disease loci have been mapped to this region: X-linked ocular albinism type 1 (OA1) and the microphthalmia with linear skin defects (MLS) syndrome. The assembly of the cosmid maps allowed us to determine the size of the deletion intervals for these two loci, which were estimated to be 110 kb for OA1 and 570 kb for MLS.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7981687 TI - Detection of point mutations in the androgen receptor gene using non-isotopic single strand conformation polymorphism analysis. German Collaborative Intersex Study Group. AB - Point mutations in the androgen receptor gene cause androgen insensitivity syndromes, clinically characterized by masculinization defects in karyotypic males due to endorgan resistance to androgenic steroids. Characterization of these mutations with single strand conformation polymorphism analysis utilizing radioactive PCR can serve as a diagnostic tool for molecular subclassification of these syndromes. It is the basis for genetic counseling and for therapeutic decisions. Here we report an improved non-radioactive single strand polymorphism analysis for rapid detection of androgen receptor gene mutations in affected individuals. In addition to previously reported mutations, 10 patients with clinical features of androgen resistance were studied. DNA was isolated from peripheral blood leucocytes and exons 1 to 8 of the coding region of the androgen receptor gene amplified by PCR. Amplification products were denatured and run on non-denaturing gels. These were subjected to fixation and silver staining. Variations were directly sequenced. In all patients a different point mutation in one of the exons was detected. While one insertion mutation was found in a patient with complete androgen insensitivity, all other mutations cause amino acid substitutions. These data suggest that the described non-radioactive single strand polymorphism analysis is a useful tool for the characterization of androgen receptor gene mutations. The omission of radioisotopes is advantageous in a clinical setting. The mutations described emphasize the clinical and molecular heterogeneity of this disease. PMID- 7981688 TI - Identification of a novel germline mutation in a FAP family. PMID- 7981690 TI - Identification of a missense mutation, single base deletion and a polymorphism in the dystrophin exon 16. PMID- 7981689 TI - Two mutations causing complete androgen insensitivity: a frame-shift in the steroid binding domain and a Cys-->Phe substitution in the second zinc finger of the androgen receptor. PMID- 7981691 TI - Topologically equivalent mutations causing dysfunctional coagulation factors VII (294Ala-->Val) and X (334Ser-->Pro). PMID- 7981692 TI - Characterization of an intron 31 splice junction mutation in the neurofibromatosis type 1 (NF1) gene. PMID- 7981694 TI - Three novel germline mutations in exons 8 and 18 of the retinoblastoma gene. PMID- 7981693 TI - New Gaucher disease mutations in exon 10: a novel L444R mutation produces a new NciI site the same as L444P. PMID- 7981695 TI - A novel mutation localized in the 3' non-HMG box region of the SRY gene in 46,XY gonadal dysgenesis. PMID- 7981696 TI - A novel donor splice site mutation associated with two mRNAs in von Hippel-Lindau disease. PMID- 7981697 TI - Pyruvate dehydrogenase deficiency caused by a four-nucleotide insertion in the E1 alpha subunit gene. PMID- 7981698 TI - Asn244His mutation of the peripherin/RDS gene causing autosomal dominant cone-rod degeneration. PMID- 7981699 TI - Maternal anticipation of DRPLA. PMID- 7981700 TI - An additional family with Startle disease and a G1192A mutation at the alpha 1 subunit of the inhibitory glycine receptor gene. PMID- 7981701 TI - Three novel rhodopsin mutations (C110F, L131P, A164V) in patients with autosomal dominant retinitis pigmentosa. PMID- 7981702 TI - Two novel mutations in exon 5 of the protein C gene in two Spanish families with thrombophilia due to protein C deficiency. PMID- 7981703 TI - Three dinucleotide repeat polymorphisms closely linked to the RET protooncogene D10S1098, D10S1099 and D10S1100. PMID- 7981704 TI - Polymorphism in the GALNS gene. PMID- 7981705 TI - XhoI and SphI RFLPs in the GALNS gene. PMID- 7981706 TI - A trinucleotide repeat polymorphism in XT00444 (D13S635E). PMID- 7981707 TI - Tetranucleotide repeat polymorphism at the D8S639 locus. PMID- 7981708 TI - Dinucleotide repeat polymorphism at the D6S510 locus. PMID- 7981709 TI - Polymorphism in exon M7 of the PTHR gene. PMID- 7981710 TI - Dinucleotide repeat polymorphism at D1S556. PMID- 7981711 TI - Dinucleotide repeat polymorphism in the TGFB2 gene. PMID- 7981712 TI - Dinucleotide repeat polymorphism for D1S70 (CRI-L461) on chromosome 1q41. PMID- 7981713 TI - Characterization of a disease-causing Glu119-Lys mutation in the low-density lipoprotein receptor gene in two Danish families with heterozygous familial hypercholesterolemia. AB - Mutations in the gene for the low-density lipoprotein receptor (LDL receptor) cause the autosomal dominant inherited disease familial hypercholesterolemia (FH). In 15 Danish patients with heterozygous FH we have screened exon 4 of the LDL receptor gene for point mutations and small rearrangements employing genomic DNA amplification and bidirectional solid-phase sequencing. Two subjects were found to be heterozygous for a guanine to adenine base substitution at nucleotide position 418 of the LDL receptor cDNA. This point mutation results in an amino acid change from glutamic acid to lysine at amino acid residue 119 in the third repeat of the cysteine-rich ligand binding domain of the mature LDL receptor. Disruption of LDL receptor function by the Glu119-Lys mutation was confirmed by site-directed mutagenesis and expression in COS-7 cells. By Western blotting the mutation was found to affect the processing of the LDL receptor protein. Using flow cytometric analysis of the transfected cells a decreased binding and internalization of LDL by the mutant receptor was documented. By means of a mutation-specific PCR-based assay the Glu119-Lys mutation was not detected in another 85 apparently unrelated Danish heterozygous FH patients. We identified six persons in the index families with the Glu119-Lys mutation cosegregating with the clinical syndrome of FH in these families. Furthermore, haplotype analysis revealed that the haplotype [SfaNI+, StuI+, AvaII-, (dTA)7] of the mutation carrying allele was the same in the two apparently unrelated patients. This indicates that the mutation has been inherited from a common ancestor. PMID- 7981714 TI - Non-phenylketonuria hyperphenylalaninaemia in Northern Ireland: frequent mutation allows screening and early diagnosis. AB - Up to 10% of newborn children with a positive Guthrie test have non phenylketonuria hyperphenylalaninaemia, i.e., mild elevation of serum phenylalanine that does not require dietary treatment. Depending on the relative frequencies of different phenylalanine hydroxylase mutations in a particular population, non-PKU HPA is usually caused by the combined effect of a mild HPA mutation and a severe PKU mutation. Presented here is a comprehensive analysis of non-PKU HPA in Northern Ireland. Of particular interest is one prevalent HPA mutation (T380M), which is present in over 70% of non-PKU HPA patients in Northern Ireland. Screening for this mutation is easy and inexpensive and can help confirm the diagnosis of non-PKU hyperphenylalaninaemia in the majority of cases at a very early stage. This may be clinically useful and reassuring for the parents. Other mutations described are V245A, L194P, and E390G. PMID- 7981716 TI - Mutations of the iduronate-2-sulfatase (IDS) gene in patients with Hunter syndrome (mucopolysaccharidosis II). AB - Genomic DNA and cDNA from fibroblasts from nine unrelated German patients with X linked iduronate-2-sulfatase (IDS) deficiency showing variable clinical manifestation were screened for point mutations and small structural aberrations. Direct sequencing revealed a splice mutation skipping exon A, one nonsense mutation, and five missense mutations concerning the exons B, F and I of the IDS gene. Several novel missense mutations were found: A68E, S426X, I485R, Q293H, and D478G. One of the point mutations eliminating a recognition site for the restriction enzyme MspI was used as a direct marker for a prenatal diagnosis. A relationship between type of mutation and clinical picture could not be recognized. PMID- 7981715 TI - Complex arylsulfatase A alleles causing metachromatic leukodystrophy. AB - Metachromatic leukodystrophy is a lysosomal storage disorder caused by the deficiency of arylsulfatase A. Sequencing of the arylsulfatase A genes of a patient affected with late infantile metachromatic leukodystrophy revealed that the patient is a compound heterozygote of two alleles carrying two deleterious mutation each. One allele bears a splice donor site mutation together with two polymorphisms and an additional missense mutation (Gly122 > Ser). The splice donor site mutation and the Gly122 > Ser substitution have been described recently but on different alleles. The other allele carries two missense mutations causing a Gly154 > Asp and a Pro167 > Arg substitution. When arylsulfatase A cDNAs carrying these mutations separately or in combination were transfected into baby hamster kidney cells expression of arylsulfatase A activity could not be detected. Linkage of mutations was verified by sequencing of the parental DNAs. Biosynthesis studies performed with the patients' fibroblasts show that the enzyme carrying both mutations is synthesized in almost normal amounts but is rapidly degraded in an early biosynthetic compartment. The occurence of two disease causing mutations on the same allele is a novel phenomenon in metachromatic leukodystrophy and as far as lysosomal storage diseases are concerned have so far only been described in Fabry disease and in the complex glucocerebrosidase alleles associated with Gaucher disease. PMID- 7981717 TI - Rapid and noninvasive screening of patients with mitochondrial myopathy. AB - In recent years, several point mutations in the mitochondrial genome have been associated with human disease. PCR Polymerase Chain Reaction/restriction endonuclease based techniques provide a reliable method for screening large numbers of specimens for many of the reported mutations. Muscle tissue usually carries the mutations and has been used in earlier studies. We describe a technique for analysis of mtDNA derived from hair follicles for a range of mutations. Both the 3243 A-->G MELAS and 8344 A-->G MERRF mutations were detected in mtDNA from hair follicles. In patients where both muscle and hair were screened, the mutation load was apparently higher in muscle. Furthermore, in patients positive for a given mutation, all the hair follicles analysed were shown to harbour the mutation, although the proportion of wild type to mutant mtDNA was found to somewhat vary. The advantages of this method are (1: six hair follicles provide sufficient mtDNA for analysis of at least 20 different mutations, and (2: specimen collection and transport to a central laboratory are easier than for other tissues. Our studies show that hair follicles constitute a reliable specimen for mitochondrial mutation screening at a diagnostic level. PMID- 7981718 TI - Genome scanning detects genetic alterations in human ovarian carcinoma. AB - Genome scanning, originally used to detect mouse mutations, is a technique which can rapidly identify differences between genomic DNA samples. The procedure is essentially a high resolution Southern analysis using a probe that hybridizes to a medium copy number (1000-2000 copies per haploid genome) repetitive element naturally dispersed throughout the genome. This technique detects genetic changes (primarily large scale genetic changes, e.g., amplifications and deletions) as differences in hybridization band intensity. The use of a probe derived from an endogenous human retroviral-like repetitive sequence, the RTVL-H element, has made genome scanning in humans feasible. In this report, the genome scanning technique was used to evaluate genomic DNA extracted from 14 frozen ovarian tumors. These included 8 high grade serous cystadenocarcinomas, 2 endometrioid carcinomas, one malignant mixed mullerian tumor, 2 Krukenberg tumors, and one tumor where histological classification was unavailable. Band amplifications were identified in 11 cases, with the most prominent amplifications observed in the high grade serous cystadenocarcinomas. In some of the cases, the amplifications involved bands of identical molecular size suggesting that similar underlying changes occurred in different tumors and are potentially associated with specific histological tumor types or clinical behavior. Band deletions were also observed in one endometrioid tumor where blood leukocyte genomic DNA was available from the same patient, allowing a direct comparison. PMID- 7981719 TI - Identification of mutations (D128G, H141L) in the liver arginase gene of patients with hyperargininemia. PMID- 7981720 TI - Molecular characterization of a DDEI melting polymorphism at the angiotensin I converting enzyme (ACE) locus. PMID- 7981721 TI - A tandem CC-->TT transition in the p53 gene of a breast cancer. PMID- 7981722 TI - Identification of mutations in four hemophilia B patients of Turkish origin, including a novel deletion of base 6411. PMID- 7981723 TI - Discussion on mutation nomenclature. PMID- 7981724 TI - Molecular basis of neurofibromatosis type 1 (NF1): mutation analysis and polymorphisms in the NF1 gene. AB - Neurobromatosis type 1 (NF1) is one of the commonest genetic disorders in humans. The gene for NF1 was cloned in 1990. The protein encoded by the gene (neurofibromin) has extensive sequence homology with GTPase-activating protein (GAP). Despite screening the whole coding region of the gene for large and medium size rearrangements and approximately 40% of the coding region of the gene for small alterations, only 45 germ-line mutations have been reported in more than 500 unrelated patients. Of these, 25 mutations involve small changes in the gene, of which 17 (68%) result in the formation of an inappropriate stop codon. A "hot spot" for mutations has not been identified. The high mutation rate at this locus and the general difficulty in identifying mutations are discussed. A complete understanding of the structure and function of the NF1 gene awaits further detailed studies of both naturally occurring and in vitro-generated mutations. PMID- 7981725 TI - Larva lights: a decade of photoaffinity labeling with juvenile hormone analogues. AB - The introduction of photoaffinity labeling into the mode of action of insect hormones and pheromones started 12 yr ago with the photoaffinity labeling of juvenile hormone binding proteins (JHBPs) from cockroaches in the laboratory of the late John K. Koeppe. Applying this technique to Manduca sexta led ultimately to a three-laboratory collaborative project that has begun to dissect the molecular basis for JH transport, metabolism, and nuclear binding and gene activation in Lepidoptera. This review provides (1) a history of the first experiments; (2) an idea of the breadth of the technique in the arthropod classes Insecta, Crustacea, and Arachnida; and (3) evidence for the depth of the technique in unearthing key details about three different types of the molecular action of JH in M. sexta. PMID- 7981726 TI - Isolation and developmental expression of the ecdysteroid-induced GHR3 gene of the wax moth Galleria mellonella. AB - Three degenerate primers were designed to match the most conserved regions within the DNA-binding domains of several selected members of the steroid hormone receptor family. Use of these primers in the polymerase chain reaction with cDNA from Galleria mellonella prepupae detected a 177 bp fragment that had 87% identity to the Manduca sexta gene MHR3 and 75% to the Drosophila melanogaster DHR3 gene, and therefore was named "GHR3". Screening of a Galleria penultimate instar cDNA library with this fragment yielded a cDNA clone that contained a 557 codon open reading frame, predicting a 62.3 kDa protein. The deduced amino acid sequence of GHR3 showed 92% overall identity with the MHR3 protein and 97 and 70% identity with DHR3 in the putative DNA- and ligand-binding domains, respectively. Hybridization of whole body RNA revealed high GHR3 mRNA levels during both the larval and pupal molts, coincident with the molt-inducing ecdysteroid pulses, and low or undetectable levels during the first half of the last instar. During the larval-pupal transformation, no GHR3 mRNA was found at the beginning of the stemmatal pigment retraction at the onset of the ecdysteroid rise; maximal levels were observed 4 h later, coincident with the peak ecdysteroid titer (over 2.3 micrograms 20E equivalents/ml hemolymph). Two mRNAs (4.6 and 3.6 kb) were detected when the ecdysteroid titer was high. Injection of 2 micrograms/gm 20E into isolated final instar larval abdomens induced the appearance of the 4.6 kb mRNA within 1.5 h; the mRNA level then reached maximum by 3 h and declined by 6 h. No 3.6 kb mRNA was detectable during that time. A 10-fold lower 20E dose caused only trace induction by 3 h. PMID- 7981727 TI - Incorporation of polyunsaturated fatty acids into phospholipids of hemocytes from the tobacco hornworm, Manduca sexta. AB - We examined the incorporation of four radioactive fatty acids, 18:1n-9, 18:2n-6, 20:4n-6 and 20:5n-3, into cellular lipids of hemocytes from tobacco hornworms, Manduca sexta. Most of the radioactivity associated with 18:1n-9 was recovered from triacylglycerols (TGs), and the radioactivity associated with 18:2n-6 was heavily incorporated into phospholipids (PLs) and TGs. Most of the radioactivity associated with the two eicosanoid-precursor polyunsaturated fatty acids (PUFAs), 20:4n-6 and 20:5n-3, was incorporated into PLs. The incorporated fatty acids were redistributed among the lipid classes during 2 h incubations. The two C20 PUFAs were moved from PLs to TGs. While 18:2n-6 underwent little change, 18:1n-9 was redistributed from TGs to PLs. Within PLs, each of the fatty acids were incorporated into phosphatidylcholine (PC), phosphatidylethanolamine (PE), phosphatidylglycerol (PtG) and phosphatidylserine/inositol (PS/PI). The incorporation patterns changed over time, indicating that the incorporated fatty acids were redistributed among the four PL fractions. The radioactivity associated with 18:1n-9 was mostly recovered from the sn-1 position of PC (59%) and PE (83%). Most of the radioactivity associated with 18:2n-6 was found in the sn-2 position of PC (88%) and PE (67%). Over 90% of the radioactivity associated with 20:5n-3 was recovered from the sn-2 position of PC and PE. Incorporation of 20:4n-6 differed from 20:5n-3 because more radioactivity was recovered from the sn-2 position of PC (93%) than PE (69%). These findings are in line with the general background of lipid biochemistry, from which incorporation of 20:4n-6 into PE marks a notable departure: 31% of the radioactivity associated with this acid was recovered from the sn-1 position of PE. These findings indicate that hemocytes from the tobacco hornworm elaborate a fatty acid incorporation system, which exhibits specificity with respect to fatty acid structure and lipid class. PMID- 7981728 TI - Characterization of two high molecular weight catechol-containing glycoproteins from pharate pupal cuticle of the tobacco hornworm, Manduca sexta. AB - Two high molecular weight cuticular proteins (MSCP120 and MSCP246) were extracted in acidic guanidine hydrochloride solution from tanning abdominal cuticle of Manduca sexta pharate pupae and purified by size exclusion high performance liquid chromatography. The apparent molecular weights were ca. 120 and 246 kDa as determined by sodium dodecyl sulfate polyacrylamide gel electrophoresis. Both proteins contained high levels of glutamate/glutamine, glycine, serine, alanine and aspartate/asparagine. MSCP120 was enriched in histidine relative to MSCP246, but the reverse was true for valine and proline. Small quantities of beta-alanine and 3,4-dihydroxyphenylalanine (DOPA), as well as other catechols and carbohydrates, also were detected in the hydrolysates. The proteins became radiolabeled when [1-14C]-beta-alanine was injected into pharate pupae, presumably by the formation of adducts with N-beta-alanyldopamine metabolites during sclerotization. Mild acid hydrolysis released N-beta-alanylnorepinephrine and 3,4-dihydroxyphenylketoethanol from both proteins. Strong acid hydrolysis yielded predominantly 3,4-dihydroxyphenylketoethylamine (arterenone), but also DOPA and dopamine. The N-terminal amino acid sequences of the two cuticular proteins were dissimilar, and that of MSCP246 was more hydrophobic than MSCP120. Both of these proteins were glycosylated with glucose, N-acetylglucosamine and traces of N-acetylgalactosamine, and MSCP246 also contained galactose. These structural glycoproteins, which occur in cuticle undergoing sclerotization, apparently react post-translationally with quinonoid tanning agents to yield catecholamine-protein adducts. Small amounts of peptidyl DOPA probably are formed by hydroxylation of tyrosyl residues. Results from this study are consistent with the hypothesis that these catechol-containing glycoproteins participate in cross linking reactions in M. sexta pupal cuticle during sclerotization. PMID- 7981729 TI - Isolation of an esterase conferring insecticide resistance in the mosquito Culex tarsalis. AB - Malathion resistance in a strain of Culex tarsalis mosquitoes is due primarily to the activity of a malathion carboxylesterase (MCE). The resistant strain was 150 times more resistant to malathion than the susceptible strain and was weakly resistant to malaoxon and carbaryl, but not to any other insecticide tested. The phenotype could be reversed with the carboxylesterase inhibitor triphenylphosphate, but no synergism was observed with either the phosphatase or polysubstrate monooxygenase inhibitors, NaF and piperonyl butoxide. MCE is expressed throughout development and is most concentrated in the gut tissues of the larvae. Subcellular fractionation indicated that MCE was localized primarily in the mitochondria of resistant insects and the cytoplasm of susceptible insects. The enzyme was purified to homogeneity from both strains, and has a molecular weight of 59,000. However, chromatofocusing indicated that resistant insects have two MCEs with pIs of 6.8 and 6.2, while susceptible insects possessed only one MCE with a pI of 6.8. The MCE unique to the resistant strain hydrolysed malathion 18 times faster than the MCE common to both strains, suggesting that malathion resistance in C. tarsalis is due to the presence of a qualitatively different esterase in the resistant strain. PMID- 7981730 TI - Isolation and identification of a pheromonotropic neuropeptide from the brain suboesophageal ganglion complex of Lymantria dispar: a new member of the PBAN family. AB - A pheromonotropic peptide was isolated from brain-suboesophageal ganglion complexes of the adult female gypsy moth, Lymantria dispar, using a 5-step HPLC purification protocol and an in vivo bioassay in Helicoverpa zea. The intact peptide was sequenced by automated Edman degradation. The L. dispar pheromone biosynthesis activating neuropeptide (Lyd-PBAN) is a C-terminally amidated 33 amino acid peptide with a molecular weight of 3881. The peptide was synthesized using Fmoc procedures. Lyd-PBAN has sequence homology with Hez-PBAN (81.8%) and Bom-PBAN-I (66.7%). All three PBANs share the C-terminal hexapeptide sequence, Tyr-Phe-Ser-Pro-Arg-Leu-NH2. In addition, the C-terminal pentapeptide sequences of Pseudaletia pheromonotropin (Pss-PT), Bombyx diapause hormone (Bom-DH), the locustamyotropins (Lom-MT) and leucopyrokinin (Lem-PK) are identical or have a high degree of homology to the C-terminus of PBANs. PMID- 7981731 TI - Fatty acid elongation in the biosynthesis of (Z)-10-heptadecen-2-one and 2 tridecanone in ejaculatory bulb microsomes of Drosophila buzzatii. AB - A fatty acid chain elongation process is involved in incorporation of saturated and unsaturated fatty acyl-CoA esters into 2-tridecanone and (Z)-10-heptadecen-2 one by Drosophila buzzatii. The microsomal fraction from mature male ejaculatory bulbs is chain-length specific and requires malonyl-CoA (or acetyl-CoA, if acetyl CoA carboxylase were present) for the chain elongation step to 2-ketones. Decarboxylation of the proposed intermediate beta-ketoacid results in 2-ketone biosynthesis. Incubation of the microsomes with the acetyl-CoA carboxylase inhibitor avidin indicated that acetyl-CoA carboxylase was present in the microsomal preparations; however, washing of the microsomal preparation removed the acetyl-CoA carboxylase activity. Fatty acyl-CoA esters were also chain elongated to produce fatty acids two and four carbons longer, suggesting that the enzymes for normal fatty acid chain elongation are also present in the microsomal fraction from ejaculatory bulbs. How much, if any, of this fatty acid chain elongation system is used for 2-ketone biosynthesis is yet to be determined. PMID- 7981732 TI - Limitations of extracorporeal shockwave lithotripsy for lower caliceal stones: anatomic insight. AB - In addition to gravity-dependent position, we suppose that other particular anatomic features may be important in the retention of stone debris in lower calices after extracorporeal shockwave lithotripsy (SWL). We analyzed the inferior-pole collecting system anatomy in 146 three-dimensional polyester resin corrosion endocasts of the pelviocaliceal system. In 74% of the cases, there was an angle of greater than 90 degrees formed between the lower infundibulum and the renal pelvis, and in 26%, the angle was 90 degrees or less. In 60%, there was a lower infundibulum 4 mm or larger in diameter. The inferior pole was drained by multiple calices disposed in two rows in 57% of the cases and by one midline caliceal infundibulum in 43%. We believe that the physician must appreciate these anatomic features when considering SWL to treat calculi located in lower calices. PMID- 7981733 TI - Electroconductive lithotripsy: principles, experimental data, and first clinical results of the Sonolith 4000. AB - The electroconductive lithotripter (ECL) is a new concept for shockwave generation in which a highly conductive solution channels the discharge between the anode and cathode. In vitro experiments showed a linear relation between the voltage setting and the pressure at F2. In vitro stone disintegration studies showed a considerable reduction in shockwave pressure variability, improved energy transfer to the stone, and a unique linear relation between fragmentation and electrode voltage without a saturation effect. This new concept has been used clinically in the Sonolith 4000 lithotripter. In 142 evaluable treatments with a 3-month follow-up, the overall stone-free rate was 82%, and the retreatment rate in stone-free patients was 10%. For stones equal or less than 10 mm, the 3-month stone-free rate, retreatment rate, and secondary procedure rate were 85%, 5%, and 0%, respectively. For stones between 11 and 20 mm, these figures were 83%, 4%, and 2%, respectively. The efficiency quotient was found to be 81% for stones equal or less than 10 mm and 78% for stones between 11 and 20 mm. These clinical results confirm the improvements in efficacy observed in vitro with very satisfactory tolerance. PMID- 7981734 TI - Histomorphologic and ultrastructural findings of shockwave-induced lesions in the isolated perfused kidney of the pig. AB - The aim of this investigation was the development of an easily reproducible model with which to evaluate shockwave-induced renal tissue damage using light and electron microscopy. Kidneys (n = 45) from freshly slaughtered pigs were perfused under physiologic conditions and treated with shockwaves at different doses (2 250 shockwaves; 12-20 kV) on the Modulith SL 20 lithotripter. The dose-dependent alterations in tissue structure were characterized by disintegration of tubular cells leading to circumscribed gap-like defects resulting from reticular fiber disruptions. Even after low shockwave doses, cellular and subcellular alterations could be observed. Our findings in this ex vivo model verify the development of considerable strictly localized, dose-dependent shockwave-induced damage of the renal parenchyma. On morphologic grounds, we cannot confirm a primary lesion or rupture of blood vessel walls as the cause of the shockwave lesions. The destruction of tubular cells in combination with disruption of peritubular and pericapillary reticular fiber coats results in capillarotubular leaks, which can explain even severe transitory macrohematuria after clinical shockwave lithotripsy without renal hematoma formation. PMID- 7981735 TI - Mechanisms of differing stone fragility in extracorporeal shockwave lithotripsy. AB - Clinical experience with extracorporeal shockwave lithotripsy (SWL) has demonstrated significant variations in stone fragility. To understand the physical mechanisms of the differences, we quantitatively determined shockwave stone interaction under clinically relevant SWL conditions for six stone compositions: calcium oxalate monohydrate (COM), struvite (MAPH), calcium apatite (CA), uric acid (UA), brushite, and cystine. We also characterized the acoustic and mechanical properties of the stones using ultrasound and microindentation techniques. Our results show that renal calculi have distinctly different acoustic and mechanical properties. Higher wave speed, Young's modulus, and fracture toughness were measured from COM and cystine stones, whereas lower values of the corresponding properties were found in CA and MAPH, and the values for brushite and UA stones were in between. Computer modeling of shockwave propagation revealed that under the same shockwave intensity, larger deformation was induced in CA and MAPH stones than in COM and cystine stones. In addition, multiple reflected tensile waves were predicted for stones with concentric layer structure, indicating their susceptibility to shockwave fragmentation. These findings elucidate the mechanisms of the differences in stone fragility observed clinically. Their implications to SWL are discussed. PMID- 7981736 TI - Verapamil limits shockwave-induced renal tubular damage in vivo. AB - Previous investigations on Madin Darby Canine Kidney (MDCK) cells demonstrated the protective effect of verapamil against shockwave-induced tubular dysfunction. In the present study, we investigated whether verapamil is also protective against shockwave-induced damage in vivo. Male rates were randomly assigned to three groups: verapamil (N = 18) (Group I), control (N = 18) (Group II), or sham treatment (N = 4) (Group III). Groups I and II were treated with 500 shockwaves to each kidney with the Dornier MFL 5000 at 18 kV. Animals assigned to Group III received only anesthesics. Verapamil was given to the animals in Group I for 5 days starting 1 day before shockwave exposure. Urine was collected for 8 hours the day before and immediately, 1.7, and 28 days after shockwave exposure (SWE) for measurement of volume, osmolality, hemoglobin, protein, N-acetyl-beta glucosaminidase (NAG), beta 2-microglobulin (beta 2M), sodium, and creatinine. Kidneys were perfused and removed for histologic study 1, 7, and 28 days after SWE in six animals of Groups I and II. Blood was taken in these rats (Day 1 after SWE) for the determination of creatinine and sodium and the calculation of the creatinine clearance (CCr) and the fractional excretion of sodium (FENa). After SWE, there was strong diuresis and significantly increased excretion of NAG and beta 2M in the controls, while urine osmolality decreased. These changes were significantly less pronounced in the verapamil-treated rats. The CCr was higher and FENa lower than in the latter group.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7981737 TI - Laparoscopic nephrectomy: an established routine procedure. AB - Between August 1992 and April 1993, 60 patients underwent laparoscopic nephrectomy in our institution for benign disease (35 hydronephrosis, 20 chronic pyelonephritis, 4 end-stage kidney, 1 renal hypoplasia). Conversion to open surgery was needed in six cases to overcome intraoperative bleeding or perirenal adhesions. The mean operative time was 3.5 +/- 1.3 hours, and the mean hospital stay was 3.2 +/- 2.1 days. No deaths occurred, but significant complications were encountered in four cases in the form of pulmonary embolism, a large hematoma, postoperative bleeding, and colonic perforation. Laparoscopic nephrectomy is a safe and effective alternative to open nephrectomy for benign renal conditions. PMID- 7981738 TI - Laparoscopic retroperitoneal needle suspension urethropexy. AB - Recent advances in laparoscopic surgery have allowed urologists to perform laparoscopic bladder suspension; however, laparoscopic suturing techniques have a steep learning curve and make the procedure more difficult and time consuming. We describe a new technique that combines extraperitoneal laparoscopic bladder neck mobilization through a single port with the ease of a needle suspension urethropexy in order to avoid the need for vaginal incisions and the use of laparoscopic suturing techniques. The procedure has been performed in four patients, all of whom are continent and voiding with complete bladder emptying. Postoperative pain was minimal, allowing most patients to be discharged the day after surgery. In the future, the procedure may be performed on an outpatient basis. PMID- 7981739 TI - Endoluminal sonography in evaluation of the obstructed ureteropelvic junction. AB - Endoluminal sonography is a technique well suited to imaging structures beyond the lumen of the hollow viscus. The development of small-diameter (6.2F), catheter-enclosed ultrasound probes has made this technique available for use within the urinary tract. It is capable of defining adjacent vessels, calculi, and masses. Ureteropelvic junction (UPJ) obstruction has been increasingly treated by incisional techniques, either nephroscopic, ureteroscopic, or radiographically controlled, with each incision at risk for causing damage to any adjacent vessel. Endoluminal sonography of the obstructed UPJ was attempted in 46 patients and completed in 45 patients, 41 with primary and 4 with secondary obstruction. Adjacent vessels could be seen in 24 patients. Twelve were located anterior or medial to the UPJ or both. Nine patients had vessels at the UPJ located laterally or anterolaterally, posterolaterally, or medially and laterally. Sonographic localization guided the choice of incision site in all patients and changed therapy in five patients. This technique also allows recognition of high insertion of the ureter into the renal pelvis. Endoluminal sonography of the obstructed UPJ is a valuable technique to determine the location and nature of associated vessels and, therefore, to guide decisions in treatment. PMID- 7981740 TI - Ureteral and bladder lesions after ballistic, ultrasonic, electrohydraulic, or laser lithotripsy. AB - Four techniques of intracorporeal lithotripsy are now available: ballistic, ultrasonic, electrohydraulic, and laser. Their therapeutic efficacies have generally been evaluated and compared, but very few data have been available on their relative risks of iatrogenic trauma to the urothelial wall. We conducted a comparative analysis of this risk by testing the pig ureteral and bladder wall with the EMS Lithoclast, Olympus ultrasonic lithotripter, Walz Lithotron EL 23, and Versa Pulse Ho:YAG Coherent Laser. We measured the number of shockwaves or the energy required to perforate the ureter and bladder by delivering shocks perpendicular to the walls. Ureteral perforation was impossible with the 1.0-mm Lithoclast transducer and the 1.5-mm ultrasound transducer. Perforation was induced after 250 shocks with the 0.8-mm Lithoclast transducer, after 110 shocks with the 3F electrohydraulic electrode, and after 0.02 kJ with the laser. Bladder perforation was impossible with the 2.0-mm Lithoclast device and the 3.4-mm ultrasound transducer but was induced after 0.04 kJ had been delivered with the laser. We evaluated the iatrogenic risk under normal conditions of use by delivering the shocks tangentially to the ureteral wall and perpendicular to the bladder wall. We sacrificed animals on days 0, 1, and 6. The immediate histologic lesions induced by the Lithoclast and the ultrasound lithotripter were similar, consisting of a moderate reduction of the epithelial layers or intraepithelial detachments. Electrohydraulic shocks induced almost complete abrasion of the urothelium, and the laser induced extensive lesions of partial or complete necrosis of the urothelial wall.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7981741 TI - Urolume in urethral stenosis: Italian Club of Minimally Invasive Urology experience. AB - A multicenter study of the patients in whom the Urolume has been implanted has been among the actions undertaken by the Italian Club of Minimally Invasive Urology (UMICLUB). For each patient, a computer information format has been prepared containing evaluation data related to the preoperative period, the endoscopic procedure, and follow-up. The collected data were computerized through unifunctional and multifunctional analysis. Of the 82 patients recruited, 76 were followed for a period ranging from 1 to 40 months. Urinoflow results dramatically improved after implantation of the endoprosthesis: peak flow rates increased by 310%, while mean flow rates increased by 294%. Incontinence and dribbling were found in 4% and 20% of the patients, respectively, and were independent of the distance between the external sphincter and the Urolume prosthesis and of the stent number and length. The cross-data elaboration seems to indicate a statistically significant relation between urethral preparation before Urolume implantation and stricture recurrence, with recurrence being more frequent after dilation. Significant correlations have not been noticed between stenosis etiology, urinary infection, type of anesthesia, and recurrence; between the type of anesthesia, stent length, and duration of hospitalization; or between stent number and position and pain. The impact of the Urolume prosthesis on sexual activity was marginal by all three measures considered (pain during erection, coitus, and ejaculation). PMID- 7981743 TI - The rise and fall of positional cloning? PMID- 7981742 TI - Odds and SODS. PMID- 7981744 TI - Retreat of the triplet repeat? PMID- 7981745 TI - No EXSCEUS. PMID- 7981746 TI - The expanded role of NF1. PMID- 7981747 TI - The structural and functional diversity of dystrophin. AB - Duchenne and Becker muscular dystrophies are caused by defects of the dystrophin gene. Expression of this large X-linked gene is under elaborate transcriptional and splicing control. At least five independent promoters specify the transcription of their respective alternative first exons in a cell-specific and developmentally controlled manner. Three promoters express full-length dystrophin, while two promoters near the C terminus express the last domains in a mutually exclusive manner. Six exons of the C terminus are alternatively spliced, giving rise to several alternative forms. Genetic, biochemical and anatomical studies of dystrophin suggest that a number of distinct functions are subserved by its great structural diversity. Extensive studies of dystrophin may lead to an understanding of the cause and perhaps a rational treatment for muscular dystrophy. PMID- 7981748 TI - Chromosomal localization of seven PAX genes and cloning of a novel family member, PAX-9. AB - In the human paired box-containing (PAX) gene family, only two members, PAX-3 and PAX-6, which are associated with Waardenburg's syndrome and aniridia, respectively have been mapped to human chromosomes. We have now isolated cosmids for six additional human PAX genes (PAX-1,-2,-5,-7,-8,-9) and a polymerase chain reaction fragment for PAX-4. PAX-9 is a novel family member which is closely related in its paired domain to PAX-1. The chromosomal location of all cloned PAX genes was determined by analysis of somatic cell hybrids and (except PAX-4) by fluorescence in situ hybridization to metaphase chromosomes. PAX-1 and PAX-7 map to chromosomal regions containing previously assigned disease loci. PMID- 7981749 TI - A mutation in the Pax-6 gene in rat small eye is associated with impaired migration of midbrain crest cells. AB - The rat small eye strain (rSey) lacks eyes and nose in the homozygote, and is similar to the mouse Sey strain with mutations in the Pax-6 gene. We isolated Pax 6 cDNA clones from an rSey homozygote library, and found an internal deletion of about 600 basepairs in the serine/threonine-rich domain. At the genomic level, a single base (G) insertion in an exon generates an abnormal 5' donor splice site, thereby producing the truncated mRNA. Anterior midbrain crest cells in the homozygous rSey embryos reached the eye rudiments but did not migrate any further to the nasal rudiments, suggesting that the Pax-6 gene is involved in conducting migration of neural crest cells from the anterior midbrain. PMID- 7981750 TI - Molecular basis of Thomsen's disease (autosomal dominant myotonia congenita). AB - Thomsen's disease (autosomal dominant myotonia congenita) has recently been linked to chromosome 7q35 in the region of the human skeletal muscle chloride channel gene (HUMCLC). Single strand conformation polymorphism analysis (SSCP) was used to screen DNA from members of four unrelated pedigrees with this disorder for mutations in HUMCLC. Abnormal bands were detected in all affected, but no unaffected individuals in three of the families. Direct sequencing revealed a G to A transition that results in the substitution of a glutamic acid for a glycine residue located between the third and fourth predicted membrane spanning segments. This glycine residue is conserved in all known members of this class of chloride channel proteins. These findings establish HUMCLC as the Thomsen's disease gene. PMID- 7981751 TI - Clustered base substitutions in CTP synthetase conferring drug resistance in Chinese hamster ovary cells. AB - Dominantly acting mutations that eliminate the allosteric regulation of CTP synthetase confer a form of multidrug resistance and a mutator phenotype to cultured Chinese hamster ovary cells. Mutations responsible for this phenotype have been identified in 23 independent strains selected for resistance to arabinosyl cytosine and 5-fluorouracil. All these mutations were due to base substitutions at seven sites within a highly conserved region of the ctps gene. This clustering should make it feasible to assess the role of such mutations in the development of drug resistance encountered in the treatment of malignant disease. PMID- 7981752 TI - Kniest and Stickler dysplasia phenotypes caused by collagen type II gene (COL2A1) defect. AB - Kniest and Stickler dysplasia are two chondrodysplasias characterized by specific phenotypes. No basic defect has been found in patients with Kniest dysplasia, whereas Stickler dysplasia is one of four chondrodysplasias for which mutations of type II procollagen gene (COL2A1) have been identified. We studied a 2-year old girl presenting with manifestations of Kniest dysplasia and her mother showing a Stickler phenotype. Analysing COL2A1 in both patients, we detected the same 28 basepair deletion spanning the 3'-exon/intron boundary of exon 12 in mother and daughter. We were able to prove a somatic mosaic status for this mutation in the mother which accounts for her milder Stickler-like phenotype. PMID- 7981753 TI - A disease locus for familial hypertrophic cardiomyopathy maps to chromosome 1q3. AB - Familial hypertrophic cardiomyopathy (FHC) is caused by missense mutations in the beta cardiac myosin heavy chain (MHC) gene in less than half of affected individuals. To identify the location of another gene involved in this disorder, a large family with FHC not linked to the beta MHC gene was studied. Linkage was detected between the disease in this family and a locus on chromosome 1q3 (maximum multipoint lod score = 8.47). Analyses in other families with FHC not linked to the beta MHC gene, revealed linkage to the chromosome 1 locus in two and excluded linkage in six. Thus mutations in at least three genetic loci can cause FHC. Three sarcomeric contractile proteins--troponin I, tropomyosin and actin--are strong candidate FHC genes at the chromosome 1 locus. PMID- 7981754 TI - Cartilage-hair hypoplasia gene assigned to chromosome 9 by linkage analysis. AB - Cartilage-hair hypoplasia (CHH) is an autosomal recessive skeletal dysplasia of unknown pathogenesis leading to short-limbed stature. Associated features include hypoplasia of hair, abnormal cellular immunity, deficient erythrogenesis, increased risk of malignancies, Hirschsprung disease, and Diamond-Blackfan type hypoplastic anaemia. We mapped the CHH gene by linkage analysis with 5 markers to chromosome 9. Multipoint linkage analysis gives a lod score of 9.94 for a location between D9S43 and D9S50. Based on strong linkage disequilibrium the closest marker, D9S50, is likely to be less than 1 cM from the gene. No heterogeneity was observed in 14 Finnish families, nor was there evidence of reduced penetrance. These results provide a starting point for the eventual cloning and characterization of the CHH gene. PMID- 7981755 TI - A gene for familial juvenile nephronophthisis (recessive medullary cystic kidney disease) maps to chromosome 2p. AB - Familial juvenile nephronophthisis (NPH) is a chronic autosomal recessive kidney disease responsible for 15% of end stage renal failure in children. NPH is frequently (16% of cases) associated with Leber amaurosis (termed Senior-Loken syndrome, SLS). Linkage analyses, performed in 22 multiplex NPH families (18 without and 4 with ocular abnormalities), have localized the gene to a region between D2S48 and D2S51 on chromosome 2p. This was confirmed using adjacent microsatellite markers, one of which (AFM220ze3 at the D2S160 locus) gave a lod score of 4.78 at theta = 0.05 in the 18 families with isolated NPH, whereas the same marker excluded linkage with SLS. These results demonstrate linkage of the purely renal form of NPH to chromosome 2p, and suggest that there may be genetic heterogeneity between NPH and SLS. PMID- 7981756 TI - Linkage of 11 beta-hydroxylase mutations with altered steroid biosynthesis and blood pressure in the Dahl rat. AB - In Dahl salt-hypertension sensitive (S) and resistant (R) strains fed a high NaCl diet, 11 beta-hydroxylase polymorphisms cosegregate with the adrenal capacity to synthesize 18-hydroxy-11-deoxycorticosterone (18-OH-DOC) and blood pressure. The R rat carries an 11 beta-hydroxylase allele that: (i) differs from those of 12 other rat strains; (ii) is associated with a uniquely reduced capacity to synthesize 18-OH-DOC; and (iii) encodes 5 amino acid substitutions in the 11 beta hydroxylase protein. The robust salt-resistance of the Dahl R rat may be due in part to reduced synthesis of the mineralocorticoid 18-OH-DOC stemming from mutations in the 11 beta-hydroxylase gene. 11 beta-hydroxylase, located on rat chromosome 7, is the first candidate gene identified in an animal model in which coding sequence mutations have been linked to the regulation of blood pressure. PMID- 7981757 TI - Genetic determinants of diastolic and pulse pressure map to different loci in Lyon hypertensive rats. AB - Several genetic loci involved in blood pressure regulation have recently been localized in experimental models of hypertension, but the manner in which they influence blood pressure remains unknown. Here, we report a study of the Lyon hypertensive rat strain showing that different loci are involved in the regulation of steady-state (diastolic pressure) and pulsatile (systolic diastolic, or pulse pressure) components of blood pressure. Significant linkage was established between diastolic blood pressure and a microsatellite marker of the renin gene (REN) on rat chromosome 13, and between pulse pressure and the carboxypeptidase B gene (CPB) on chromosome 2. These findings show that two independent loci influence different haemodynamic components of blood pressure, and that pulse pressure has a specific genetic determination. PMID- 7981760 TI - Safeguarding your career. PMID- 7981758 TI - HLA class II alleles and susceptibility and resistance to insulin dependent diabetes mellitus in Mexican-American families. AB - The role of HLA class II alleles in genetic predisposition to insulin dependent diabetes mellitus (IDDM) was examined by PCR/oligonucleotide probe typing of 42 Mexican-American IDDM families derived from Hispanic Caucasians and Native Americans. All high risk haplotypes (HLA-DR3 and DR4) were of European origin while the most strongly protective haplotype (DRB1*1402) was Native American. Of the 16 DR-DQ DR4 haplotypes identified, only those bearing DQB1*0302 conferred risk; the DRB1 allele, however, also markedly influenced IDDM risk. The general pattern of neutral and protective haplotypes indicates that the presence of Asp 57 in the HLA-DQ beta chain does not confer IDDM protection per se and indicates that both DRB1 and DQB1 influence IDDM susceptibility as well as protection. PMID- 7981759 TI - Targeting in linear DNA duplexes with two complementary probe strands for hybrid stability. AB - A new in vitro hybridization reaction targets two short complementary RecA protein-coated DNA probes to homologous sequences at any position in a linear duplex DNA molecule. Stable hybrids are obtained after RecA protein removal when both complementary probe strands are present in a four-stranded hybrid, but not when one probe strand is present in a three-stranded hybrid. In four-stranded hybrids with one probe strand biotinylated and the other radiolabelled, the deproteinized hybrids can be isolated and detected by affinity capture on streptavidin-coated magnetic beads. RecA-mediated targeting of complementary biotinylated DNA probe strands allows the affinity capture of 48.5-kilobase duplex lambda genomic DNA. These reactions provide a means of isolating any desired duplex gene or chromosomal DNA fragment. PMID- 7981761 TI - Williams takes her leave. Interview by Teresa O'Connor. PMID- 7981762 TI - A union leader. Interview by Kathy Stodart. PMID- 7981763 TI - When care turns to despair. PMID- 7981764 TI - Where have all the leaders gone? PMID- 7981766 TI - The effect of psychotropic drugs on the interaction of protein kinase C with second messenger systems in the rat cerebral cortex. AB - The paper describes and compares the influences of the antidepressants (imipramine, mianserin, citalopram), electroconvulsive shock, and the neuroleptics (haloperidol, chlorpromazine and spiperone) on the systems of second messengers related to adrenergic receptors in rat cerebral cortex, measured by generation of cyclic AMP and inositol phosphate (IP), and their influence on the effects of activation of protein kinase C (PKC) by its synthetic activator, phorbol ester (TPA). The effect of PKC-stimulation was expressed as a reduction of noradrenaline-stimulated IP accumulation and, on the other hand, as an enhancement of cyclic AMP response under stimulation with noradrenaline and isoproterenol. When administered chronically, the described antidepressants (unlike the neuroleptics) augmented IP accumulation or left it unchanged, but they reduced PKC's negative feedback with the alpha 1-adrenoceptor. PKC-induced potentiation of cyclic AMP's response to beta-adrenergic receptor stimulation was unchanged or enhanced, while the antidepressants reduced the generation of this second messenger. However, citalopram increased cyclic AMP generation and reduced PKC potentiation. Taking into account the role of PKC in adrenergic receptors cross-talk explains why, despite antagonization of alpha 1-adrenoceptors and induction of beta down-regulation by some antidepressants, enhancement of the process of noradrenergic neurotransmission can occur as a final effect of the action of these drugs. It was found that the action of antidepressants is largely related to the adrenergic system, even when their action on this system is not direct and is accomplished by their influence on another neurotransmitting system, e.g. the serotonergic system. PMID- 7981765 TI - Caring for a lymphoma patient. PMID- 7981768 TI - Non-deterministic individual responses to receptor-selective opioid agonists. AB - To assess within a single rat strain individual variability of analgesic responses to sub-ED50 doses of receptor-selective opioids, we measured: 1) tail flick latency (TFL) responses after intrathecal (ith) injection of delta, mu, and kappa agonists administered serially; 2) TFL and tail pinch latencies (TPch) after intravenous (iv) mu and kappa agonists; and 3) TFL and TPch after iv agonists of mu or combined mu + delta selectivity. Mean values in each study confirmed an analgesic response, but individual TFL and TPch responses were chaotic and, within each study, rank order correlations between TFL and TPch values within or between drugs were insignificant. Our results suggest a hypothesis that such responses are intrinsically nondeterministic because- resembling other complex dynamic systems--they are generated by stochastic receptor-transmitter interactions that in turn evoke a series of nonlinearly coupled cellular and neural events. PMID- 7981767 TI - Antagonism of (+)WAY 100135 to behavioral, hypothermic and corticosterone effects induced by 8-OH-DPAT. AB - The 5-HT1A antagonistic properties of (+)-N-tert-butyl-3-[4-(2 methoxyphenyl)piperazin-1-yl]-2-phenyl pro panamide ((+)WAY 100135) were studied. Its effect on the 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT)-induced behavioral syndrome (flat body posture and reciprocal forepaw treading) in reserpine-pretreated rats, the stimulus effect in a drug discrimination model in rats, the lower lip retraction in rats, the hypothermia in mice and secretion of corticosterone in rats, i.e. responses mediated by 5-HT1A receptors, were examined. (+)WAY 100135 administered in doses up to 10 mg/kg dose-dependently antagonized all the above responses to 8-OH-DPAT, the lowest effective doses ranging from 1.25 to 2.5 mg/kg. At the same time, (+)WAY 100135 alone given in doses of 1.25-10 mg/kg did not mimic the activity of 8-OH-DPAT in the tests used. Our results indicate that (+)WAY 100135 is an antagonist of pre- and postsynaptic 5-HT1A receptors devoid of agonist properties. PMID- 7981769 TI - The influence of the kappa agonist-spiradoline (U62066E) on the analgesic activity of some opioids at the spinal level. AB - Male Wistar rats were treated with morphine (MP) or pentazocine (PT) subcutaneously (sc) and then intrathecally (it) with a specific kappa receptor agonist spiradoline (U62066E). In another series of experiments methionine-(MENK) or leucine-enkephalin (LENK) were injected it with U62066E simultaneously. Then antinociceptive effect on thermal stimulus was measured 1 h using the tail immersion test. MP or LENK induced analgesia was enhanced by U62066E during the first 30 min of observation. MENK analgesic activity was potentiated by kappa receptor agonist only up to 5 min. U62066E acted biphasically on PT antinociceptive effect. These results suggest that kappa opioid receptors may participate in antinociceptive action of MP and LENK and in small degree for analgesic effect of PT and MENK at the spinal level. PMID- 7981770 TI - The influence of naloxone on the effects of adenosine receptor agonists in analgesic tests and binding studies. AB - Naloxone (1 mg/kg ip) reduced analgesic effect of R-phenylisopropyladenosine (R PIA-0.2 mg/kg sc) in hot plate and tail-immersion tests in mice and in tail immersion test in rats. Also the effect of 2-chloroadenosine (2-CADO-2 mg/kg sc) was significantly reduced by naloxone in mice in both nociceptive tests. Naloxone induced partial reduction of analgesic effects of 5'-N-ethylcarboxamideadenosine (NECA-0.02-0.05 mg/kg sc) in mice and rats. Binding studies revealed that the affinity of adenosine agonists (R-PIA and NECA) to opioid receptors was about 5000 times weaker than the corresponding affinity of naloxone. PMID- 7981771 TI - Conjugated dienes in selected organs of mice treated with doxorubicin and 4'-epi doxorubicin. Part I. AB - The purpose of this study was to evaluate in vivo the influence of doxorubicin (DOX) and its less cardiotoxic analog 4'-epi-doxorubicin (EPI) on lipid peroxidation. The content of conjugated dienes (CD) in heart, liver and lungs of Balb/c mice was measured over a 24-h period at various time-points [1.5 and 24 h] after a single intravenous injection of either DOX or EPI. A statistically significant (p < 0.01) increase in CD levels was seen in mice heart extracts 24 h after treatment with DOX. No statistically significant increase in CD content was seen in any other group of animals treated with either DOX or EPI up to 24 h. The data presented in this paper indicate that DOX, but not EPI, induces lipid peroxidation in cardiac muscle. PMID- 7981773 TI - Muscle rigidity induced by the opioid analgesic tramadol, but not by the non opioid flupirtine. AB - The influence of high doses of two analgesic drugs, tramadol and flupirtine on the electromyographic activity in the gastrocnemius soleus muscles was examined. Tramadol (100-200 mg/kg po) dose-dependently induced a tonic electromyographic activity, which is generally accepted as a model of the opiate-induced muscle rigidity. That effect was antagonized by intraperitoneal injection of naloxone (0.8 mg/kg ip). On the other hand, flupirtine even in the high doses (100-200 mg/kg po) did not induce any tonic electromyographic activity. The obtained results confirm an opiate-like action of tramadol, but not that of flupirtine, on the muscle tension. PMID- 7981774 TI - The effect of MK-801 and imipramine on beta-adrenergic and 5-HT2 receptors in the chronic mild stress model of depression in rats. AB - Chronic exposure (8 weeks) to sequential application of mild stressors caused the increase in the density (Bmax) of beta-adrenergic and 5-HT2 receptors in the rat cerebral cortex. MK-801 given chronically (5 weeks) decreased beta-adrenergic receptors density in both control and stressed rats, whereas it decreased the density of 5-HT2 receptors in control rats only. On the other hand, imipramine administered for 5 weeks reduced the number of beta-adrenergic and 5-HT2 receptors in both control and stressed rats. PMID- 7981775 TI - Co-administration of nifedipine with neuroleptics prevents development of activity changes during withdrawal. PMID- 7981772 TI - The influence of doxorubicin and 4'-epi-doxorubicin on lipid peroxidation in mouse heart, lungs and liver. Part II. AB - Influence of doxorubicin (DOX) and its less cardiotoxic analog 4'-epi-doxorubicin (EPI) on the peroxidation of cellular components was evaluated in vivo. Previous experimental work performed at our laboratory indicates that DOX, but not EPI, induces a marked increase in conjugated dienes formation (CD) in mice hearts exposed to a single intravenous dose (30 mg/kg) of that drug. Therefore, in the present study lipid peroxidation after treatment with these anthracyclines, was evaluated and compared in vivo by measuring the content of malondialdehyde (MDA) in heart, liver and lungs of Balb/c mice over 48-h period at various time-points: 5, 24 and 48 h after a single intravenous injection of either DOX or EPI. A statistically significant increased formation of MDA was found after both DOX and EPI in mice heart, lung and liver homogenates. DOX caused a relatively higher increase in MDA formation than did EPI. The results obtained in this study indicate that both DOX and EPI induce peroxidation of tissue components in vivo as shown by the increase in the formation of MDA. However, only DOX induces significant increase in lipid peroxidation in cardiac muscle, as assessed by the formation of CD. The results also suggest that peroxidation of other tissue components may be responsible for anthracycline-induced cardiotoxicity. PMID- 7981776 TI - Rewarding properties of non-competitive and competitive NMDA antagonists as measured by place preference conditioning in rats. AB - The conditioned place preference paradigm was used to evaluate rewarding properties of non-competitive (MK-801) and competitive (CGP 37849) antagonists of NMDA receptors. Both MK-801 (0.3 mg/kg ip) and CGP 37849 (5, 10, 20 mg/kg ip), administered in association with the initially non-preferred (white) side of the two-arms chamber, caused a significant increase in the time spent on that side in a post-conditioning test. These results show that both non-competitive and competitive antagonists of NMDA receptors are rewarding in animals and may therefore have an abuse potential in humans. PMID- 7981777 TI - Effects of human growth hormone on fuel utilization and mineral balance in critically ill patients on full intravenous nutritional support. AB - PURPOSE: The effects of recombinant human growth hormone (GH) on fuel utilization, mineral and fluid balance in critically ill patients were studied. METHODS: Twenty patients requiring mechanical ventilation and receiving standard parenteral nutrition were studied. GH 0.1 mg/kg/day (n = 10) or placebo (n = 10) was administered as continuous intravenous infusion for 3 days. Plasma mineral levels, urinary nitrogen, and mineral excretion were measured. Indirect calorimetry was used to calculate energy production rate and fuel utilization. RESULTS: Insulin-like growth factor I concentrations increased: day 4 GH, 18.9 +/ 7.0 ng/mL; controls 11.6 +/- 3.2 ng/mL (P < .05). During GH administration, the nitrogen balance became zero, whereas it remained negative in controls (P = .03). Fuel utilization did not differ between the groups. Neither did oxygen consumption, carbon dioxide production, or the respiratory quotient (RQ). Nonprotein RQ showed a tendency to decrease in the GH group, whereas an increase was present in controls. Mineral balance improved in both groups. Phosphate balance improved by 250% in the GH group (P = .054). CONCLUSIONS: GH administration in critically ill patients reduces nitrogen loss and improves phosphate retention but does not have an important effect on fuel utilization. PMID- 7981778 TI - Effect of two tidal volumes on oxygenation and respiratory system mechanics during the early stage of adult respiratory distress syndrome. AB - PURPOSE: To study the effect of two tidal volumes on gas exchange, lung mechanics, and hemodynamics in 12 patients with acute respiratory distress syndrome (ARDS) within the first 72 hours of mechanical ventilation. METHODS: Tidal volume (VT) was increased by 40% from the initial value at fixed positive end-expiratory pressure (PEEP) and matched minute ventilation by adjusting the respiratory rate (RR) of the ventilator. Initial VT and RR were 592 +/- 42 mL and 19 +/- 1 min-1, respectively. High VT amounted to 825 +/- 54 mL with a RR of 12 +/- 1 min-1. RESULTS: We found that at high VT (1) the index of oxygenation increased from 0.22 +/- 0.03 to 0.32 +/- 0.04 (P < .001) with a parallel decrease in the right to left venous admixture from 0.26 +/- 0.02 to 0.23 +/- 0.02 (P < .001), and in the ratio of physiological dead space to tidal volume (VDS/VT) from 0.53 +/- 0.05 to 0.46 +/- 0.04 (P < .01), without impairment to hemodynamics and (2) respiratory system compliance improved significantly from 34.8 +/- 2.8 mL/cm H2O to 37.2 +/- 2.9 mL/cm H2O (P < .05). In 4 patients, we performed pressure volume curves on PEEP with the ventilator finding an upward concavity reflecting progressive alveolar recruitment with increasing inflation volume in 3. CONCLUSIONS: High-tidal ventilation in the early stage of ARDS improved gas exchange, suggesting recruitment during the inspiratory phase. However, the benefit of better oxygenation should be weighed against the potential risk of barotrauma induced at high VT. PMID- 7981779 TI - Regional blood flow distribution in endotoxin-treated dogs: modification by ibuprofen. AB - PURPOSE: The aim of this study was to determine whether the improved hemodynamic profiles reported with cyclooxygenase inhibition during sepsis include improvements in tissue perfusion is unknown. Our hypothesis was that cyclooxygenase inhibition with ibuprofen will prevent the endotoxin-induced alterations in regional blood flow distribution from developing and/or restore the endotoxin-induced loss of responsiveness to intravascular volume expansion. METHODS: We measured cardiac output, regional blood flow, and total systemic shunt flow in dogs using radiolabeled 15-microns microspheres. These parameters were assessed in control (N = 10) and endotoxin-treated animals (N = 7). Additional endotoxin-treated animals (N = 7) were also pretreated with ibuprofen. RESULTS: Compared with controls, endotoxin-treated animals exhibited marked reductions in blood flow to most systemic organs that were not reversed with large, intravenous saline infusions (ie, isotonic saline; 40 mL/kg; N = 4). By contrast, although ibuprofen pretreatment (12.5 mg/kg; N = 7) completely prevented the reductions in mean arterial pressure caused by endotoxin from occurring, it did little to prevent the development of endotoxin-induced alterations in regional blood flow distribution. Nonetheless, in contrast to the endotoxin-treated animals, there were significant increases in cardiac output and blood flow to several organs after saline infusion in the ibuprofen-pretreated animals. CONCLUSIONS: Cyclooxygenase inhibition with ibuprofen has few direct effects on regional blood flow distribution after endotoxin. However, cyclooxygenase inhibition with ibuprofen does attenuate the endotoxin-induced decrease in vascular responsiveness to intravenous saline infusion. PMID- 7981780 TI - A noninvasive method for monitoring cerebral perfusion during cardiopulmonary resuscitation. AB - PURPOSE: This study evaluates the use of transcranial Doppler (TCD) ultrasound in assessing the changes experienced by the cerebral circulation during cardiopulmonary resuscitation (CPR) and compares it with measurements of internal carotid artery (ICA) flow rates (ultrasonic flow-meter measurements) and cerebral blood flow (CBF) (radioactive-microsphere measurements) in a porcine cardiac arrest model undergoing closed chest CPR. METHODS: Sixteen piglets were anesthetized and subjected to TCD monitoring, ICA flow-rate measurements, and CBF measurements during CPR following induction of ventricular fibrillation. A total of 14 comparisons between TCD and CBF measurements, and 36 comparisons between TCD and ICA flow measurements were performed. Correlations were determined using Pearson's method, and the validity of the correlation was determined using Bonferoni's adjusted probabilities. RESULTS: The correlation between mean cerebral blood flow velocity and mean total ICA flow rate was 0.67 (P < .01). The correlation between peak systolic blood flow velocity and CBF was 0.76 (P = .02). CONCLUSIONS: TCD can provide on-line information about cerebral perfusion during CPR. PMID- 7981781 TI - Prostacyclin improves glucose utilization in patients with sepsis. AB - PURPOSE: In patients with sepsis, impaired glucose metabolism and altered microcirculatory blood flow are common findings. Prostacyclin (PGI2) improves tissue oxygenation, indicated by enhanced oxygen delivery (DO2) and oxygen uptake (VO2). The purpose of this study was to explore whether these effects are associated with improved glucose utilization. METHODS: In 7 patients with sepsis, glucose metabolism was analyzed using dideuterated and 13C-labeled glucose and isotope dilution mass spectrometry. All patients received total parenteral nutrition with glucose covering 60% to 70% of the predicted energy expenditure and needed continuous intravenous insulin (40 microU.kg-1.min-1) to keep blood glucose concentrations below 10 mmol.l-1.VO2 and carbon dioxide production (VCO2) were continuously measured directly from the respiratory gases via indirect calorimetry. After equilibration of the infused labeled glucose with body glucose pool, baseline variables of glucose metabolism were assessed: glucose oxidation rate was determined from the enrichment of 13CO2 in the expired gas during primed constant infusion of [U-13C]glucose, glucose turnover rate (Ra) from the plasma enrichment of simultaneously infused [6,6-2H2]glucose. Endogenous glucose production rate was calculated as the difference between Ra and glucose infusion rate. Then, we examined the effect of PGI2 infusion (5 to 12.5 ng.kg-1.min-1) on glucose metabolism and gaseous exchange. RESULTS: The PGI2-induced increase in DO2 (from 15.8 to 17.7 ml.kg-1.min-1; P < .05) resulted in an increase in directly measured VO2 from 5.0 to 5.3 ml.kg-1.min-1 (P < .01) whereas VCO2 remained unchanged. Although glucose turnover and production rates remained constant, glucose oxidation rate increased significantly from 1.21 to 1.38 mg.kg 1.min-1 (P < .02). CONCLUSIONS: Improving tissue perfusion and oxygenation with PGI2 may also modify the impaired glucose metabolism by increasing glucose oxidation rate in patients with sepsis, suggesting enhanced adenosine triphosphate production. PMID- 7981782 TI - The serum osmole gap. AB - Estimation and measurement of serum osmolality can be of value in the clinical management of certain forms of critical illness. Osmolality is a measure of the concentration of osmotically active particles, or solutes, in a solution. Only low-formula weight ions and uncharged molecules that are present in relatively high concentrations contribute significantly to serum osmolality. Serum osmolality can be easily estimated from the three major osmotic constituents of normal serum (sodium, urea, and glucose) by a simple formula. An understanding of serum osmolality, its laboratory measurement, its bedside estimation, and the concept of the osmole gap, is crucial in making a preliminary diagnosis of methanol and ethylene glycol intoxication, as well as a few other related compounds. There are important caveats to this use of the osmole gap, because under certain circumstances both false-positive and false-negative interpretations may occur. The osmole gap may also be helpful for confirming pseudohyponatremia, as a gauge for dosing mannitol and glycerol when used to treat intracranial hypertension, and as a prognostic indicator in circulatory shock. PMID- 7981783 TI - Splanchnic tonometry: a review of physiology, methodology, and clinical applications. AB - The objective of this article is to review splanchnic tonometry. The English literature, involving both animal and human studies, was used for review, with emphasis on papers on physiological and methodological principles and clinical applications. Tonometry involves the measurement of intraluminal PCO2 as a measure of mucosal PCO2 in the gastrointestinal tract via a catheter in, for instance, stomach or sigmoid colon, and the calculation, with help of the blood bicarbonate content and the Henderson-Hasselbalch equation, of the mucosal pH (pHi). The latter is considered as a relatively simple index of the adequacy of mucosal blood flow. Concerning methodology, it is still unclear whether acid secretion should be inhibited for proper assessment of PCO2 in the stomach. Buffering of bicarbonate by gastric acid may elevate the intraluminal PCO2 independently from mucosal PCO2, thereby confounding pHi as a measure of perfusion adequacy. This can be prevented by inhibition of acid secretion. Authors have raised doubts whether the composite variable pHi is of additive value to the acid-base status of arterial blood, so that it is unclear whether a subnormal pHi is a specific and sensitive indicator of mucosal ischemia, as suggested by others on the basis of a decline in the pHi along the gastrointestinal tract in animals subjected to vascular occlusion or circulatory shock. Moreover, tissue PCO2 depends on the PCO2 of supplying blood. Conversely, the bicarbonate concentration in ischemic mucosa may not equal that in arterial blood. Taken together, an elevated tonometer fluid arterial blood PCO2-gradient might be a more sensitive and specific indicator of mucosal ischemia than a decrease in the pHi, analogous to an increase in tissue PCO2 and widening of the venoarterial PCO2 gradient during various types of hypoperfusion, in animals and humans. Although splanchnic ischemia is an early event in shock, the sensitivity and specificity of this index for mucosal ischemia and its clinical value, relative to that of the pHi, have not been formally evaluated yet. Nevertheless, the pHi has been suggested to be of predictive value for gastrointestinal complications, multiple organ failure, success or failure of weaning from mechanical ventilation, and outcome in critically ill patients. Tonometry may be a useful monitoring technique to guide treatment and to improve survival. Splanchnic tonometry is a relatively simple, noninvasive, and thereby promising technique to monitor the critically ill. However, some aspects need further evaluation before the technique can be advocated for routine use. PMID- 7981784 TI - Endogenously generated active oxygen species and cellular glutathione levels in relation to BHK-21 cell proliferation. AB - In BHK-21 cells (baby hamster kidney fibroblasts) cellularly generated active oxygen species such as hydrogen peroxide and superoxide appear to be important growth regulatory signals as judged from the growth inhibitory effects of catalase, superoxide dismutase and superoxide dismutase mimics. These active oxygen species may contribute a novel redox system of regulatory control superimposed upon established growth signal pathways. This may be achieved by direct oxidative modification of cell regulatory proteins such as transcription factors or protein kinases or indirectly through, for example alterations in levels of glutathione (GSH). This latter possibility is suggested from observations that catalase, or superoxide dismutase treatment of BHK-21 cells brings about increased cellular levels of GSH. However during the normal growth phase cellular levels of GSH actually decline although this effect can be partly reversed by N-acetylcysteine and by mercaptosuccinate which also impair proliferation of these cells. PMID- 7981786 TI - The bactericidal action of peroxides; an E.P.R. spin-trapping study. AB - E.P.R. spin trapping has been employed to study radical production during the bactericidal action of three peroxide compounds (peracetic acid, 4-percarboxy-N isobutyltrimellitimide and magnesium monoperoxyphthalate) upon both Gram negative (Escherichia Coli) and Gram positive (Staphylococcus Aureus) bacteria. Use of the spin trap 5,5-dimethyl-1-pyrroline N-oxide (DMPO) has allowed direct detection of both carbon-centred and hydroxyl radicals, which are produced at varying rates for the different bacteria/peracid systems studied. The inhibition of bactericidal action, by DMPO and two antioxidants, Vitamin C and Trolox C, indicates that radicals are the lethal species and evidence is presented which suggests that radical production is internal to the bacterial cell. Hydroxyl radicals are believed to be the lethal species. The effect of added iron chelators and haem protein inhibitors indicates that iron species and haem proteins in particular are involved. A marked variation is found in observed hydroxyl-radical adduct signals with both the nature and concentration of peracid. A strong inverse correlation is found between the concentration of the observed radical adduct signal and the relative strength of the peroxide as a bactericide; use of a stable nitroxide as a radical scavenger confirms that strong bactericides produce radicals at a much faster rate than weak bactericides. Plots of radical generation versus time are correlated with % bacterial kill, offering further evidence that hydroxyl radicals are the lethal species. PMID- 7981785 TI - Radiation damage to the erythrocyte membrane: the effects of medium and cell concentrations. AB - Human erythrocytes suspended in plasma, or in phosphate buffered saline (PBS), were exposed to ionizing radiation. Potassium leakage from irradiated erythrocytes is significantly higher in PBS than in plasma. The potassium leakage decreases when PBS is gradually replaced by plasma. These findings suggest that some of the plasma constituents have radioprotective properties. The potassium leakage per cell is independent of the hematocrit, Hct. The potassium leakage is attributed to the formation of radiation defects in the membrane. Analysis of the effect of radiation dose, plasma and cell concentrations on the product of the number and surface area of the radiation defects indicates that the radiation damage is mainly due to the direct formation of free radicals in the cell membrane. The radioprotective effect of plasma is attributed to surface reactions of these free radicals with plasma constituents adsorbed on the membrane. PMID- 7981787 TI - Rapid free radical reduction in the perfused rat liver. AB - The reduction of nitroxide free radicals was investigated in detail by Electron Paramagnetic Resonance (EPR) spectroscopy in perfused liver. The nitroxide free radical was rapidly reduced to the corresponding hydroxylamine more efficiently at the lower flow rate of 8 [ml/min], while at higher flow rates, the amount of reduced nitroxide showed a significant decrease. Oxidation of hydroxylamine using hydrogen peroxide provided dynamic information concerning the reduction of the free radical within the liver. In addition, liver homogenates were also investigated to determine the level of nitroxide uptake. The results suggested that a portion of the infused nitroxide was taken up by the liver and cleared from the circulation. PMID- 7981788 TI - Superoxide scavenging activity of spin-labeled nitrosourea and triazene derivatives. AB - Superoxide scavenging activities (SSA) of newly synthesized spin-labeled nitrosourea and triazene derivatives, and their precursor nitroxides were investigated by the ESR/spin-trapping method using the spin trap 5,5-dimethyl-1 pyrroline-N-oxide (DMPO) and hypoxanthine/xanthine oxidase as the superoxide generating system. The spin-labeled nitrosoureas, triazenes and their precursor nitroxides exhibited excellent SSA, whereas clinically used nitrosourea and triazene, which do not contain the nitroxide moiety, did not show any SSA. Furthermore, it was deduced that these nitroxides scavenge superoxide by redox cycling between nitroxide and corresponding hydroxylamine. PMID- 7981789 TI - The antioxidant action of synthetic oestrogens involves decreased membrane fluidity: relevance to their potential use as anticancer and cardioprotective agents compared to tamoxifen? AB - The synthetic oestrogens diethylstilboestrol, hexoestrol and 17 alpha ethynyloestradiol are known to be good antioxidants, and we now report that they decrease membrane fluidity, in ox-brain phospholipid liposomes. The order of effectiveness was diethylstilboestrol > hexoestrol > 17 alpha-ethynyloestradiol and a good positive correlation was demonstrated between decreased membrane fluidity and antioxidant ability (measured as inhibition of liposomal lipid peroxidation: correlation coefficient, r = 0.99). This ability of diethylstilboestrol, hexoestrol and 17 alpha-ethynyloestradiol to decrease membrane fluidity is suggested, therefore, to be the mechanism of their antioxidant action. The membrane-modulating antioxidant action of these synthetic oestrogens is compared to that of tamoxifen and their potential use as anticancer and cardioprotective agents is discussed. PMID- 7981790 TI - Achilles tendon tenodesis to prevent heel pad migration in the Syme's amputation. AB - In an attempt to prevent migration of the heel pad, 11 patients underwent a combined Syme's amputation and Achilles tendon tenodesis between December 1989 and April 1992. Ten patients healed the Syme's amputation, and one patient failed to heal the surgical wounds and required a below-knee amputation. In all 10 successful Syme's cases, the heel pad has remained stable with no migration, and no skin breakdown at an average follow-up of 18.5 months. Published series of Syme's amputations report that the incidence of heel pad migration is between 7.5% and 45%, and occurs primarily in the post-operative or early rehabilitation stage. We believe that tenodesis of the Achilles tendon is a technically easy addition to the Syme's amputation, that it keeps tension off of the incision during healing, and that it prevents migration of the heel pad. PMID- 7981791 TI - Arthrodesis of the first metatarsophalangeal joint with Vitallium plate fixation. AB - Forty-seven patients (58 feet) underwent first metatarsophalangeal joint fusion with a small Vitallium plate (Howmedica, Inc., Rutherford, NJ). Congruous joint surfaces were prepared with either cone-shaped or cup-shaped reamers. At an average follow-up of 19.2 months, 98% (57 feet) were successfully fused. Ninety three percent (54 feet) noted good or excellent results. Plate removal was necessary in only 7% (4 feet) of cases. Complications included nonunion with plate breakage in 2% (1 foot) and delayed union in 2% (1 foot) of cases. This technique was useful and predictable in achieving successful fusion of the first metatarsophalangeal joint. PMID- 7981792 TI - Posterior ankle impingement. AB - Thirty cases of posterior ankle impingement in 28 patients were treated over a 10 year period (1982-1992). All conditions were caused by forced plantar flexion. An os trigonum or posterior process fracture was demonstrated radiographically in 63% of these cases, and an intact posterior process was demonstrated in 33%. Ten cases were lost to follow-up. Of the remaining 20 cases, in 18 patients 12 (60%) improved with nonoperative treatment; 8 (40%) required operative excision. The results were good to excellent in 7 patients and fair in 1 patient. Operative excision for the treatment of recalcitrant posterior ankle impingement can relieve symptoms and allow a return to full preinjury activities. PMID- 7981794 TI - Plantar pressure distribution patterns of young school children in comparison to adults. AB - Peak pressures and relative loads were determined under the feet of 125 children between 6 and 10 years of age. These results were compared with previously published data from 111 adults. A capacitive pressure distribution platform with a resolution of 2 sensors/cm2 was used for data collection during walking. As compared with the group of adults, the school children showed considerably lower peak pressures under all anatomical structures. Larger foot dimensions with respect to body weight result in reduced foot pressures for the children by distributing the ground reaction forces across larger contact areas. With increasing age, a medial load shift in the forefoot could be observed for the older children. Data analysis of the pressures under the midfoot revealed that the longitudinal foot arch development is almost complete before the age of 6. Contrary to the findings in adults, body weight was identified to be of major influence on the magnitude of the pressures under the feet of school children. No differences were found for the foot pressures between boys and girls. PMID- 7981793 TI - Severe obesity: effects on foot mechanics during walking. AB - The purpose of our study was to determine the effects of severe obesity on the foot mechanics of adult females. Twenty-nine adult females between the ages of 20 and 48 years volunteered as subjects for this investigation. The subjects were separated into a severely obese (O) group (body mass index = 41.14 +/- 2.61; N = 16) and a normal weight control group (body mass index = 20.84 +/- 0.47; N = 13). A Locam camera (100 Hz) positioned perpendicular to the subjects' posterior aspect was used to film the rearfoot movement of the subjects during the final 15 sec of a 10 min treadmill walk. The O group had a significantly greater touchdown angle (P = .05), more total eversion range of motion (P = .001), and a faster maximum eversion velocity (P < .001). Moreover, analysis of dynamic foot angles indicated that the O group had significantly (P = .003) more forefoot abduction. Finally, anthropometric data revealed statistically different (P < .001) Q angle measurements between the O and control groups. The results of this study suggest that severely obese females have significantly greater rearfoot motion, foot angle, and Q angle values than normal weight females. PMID- 7981795 TI - Intraosseous hemangioma of the talus: a case report. AB - A 35-year-old female patient presented to us with a lesion in the talus that on AP-roentgenographic view simulated an osteoid osteoma. Final pathology revealed it to be an intraosseous hemangioma. An intraosseous hemangioma at this site is extremely uncommon and has not been previously reported. PMID- 7981796 TI - Ossification of the Achilles tendon: a case report. AB - Ossification of the Achilles tendon is a rare condition. We recently treated a patient with ossification of bilateral Achilles tendons. The patient was a 50 year old male whose chief complaint was discomfort around the Achilles tendon. He had a previous history of treatment of bilateral club feet. On the roentgenograms, the length of the bony mass in the Achilles tendon was 5.5 cm on the right side and 1.5 cm on the left side. The left side was treated by surgical removal of a bony mass and suture of the tendon. Microscopic examination of the extirpated specimen revealed bone formation through enchondral and intramembranous ossification in the Achilles tendon. PMID- 7981798 TI - Late infections of the foot due to incomplete removal of foreign bodies: a report of two cases. AB - Foreign bodies in the foot can remain silent for years before presentation. We describe two foreign body infections in the feet of two patients more than 18 years after the initial insult. These cases emphasize the need for careful evaluation of patients with an unexplained infection in the foot, and thorough debridement, when surgical treatment is necessary. PMID- 7981799 TI - The patellar tendon-bearing brace as treatment for neurotropic arthropathy: a dynamic force monitoring study. PMID- 7981797 TI - Intramural leiomyosarcoma of the dorsal pedal vein: a clinical mimicry of ganglion. AB - A 75-year-old woman presented with a ganglion-like nodule on the dorsal aspect of the right foot. A 2.5 x 1.5 cm, saccular and malleable tumor, that was in continuity with the dorsal venous arch, was completely resected. It was characterized by a diffuse intramural and circumferential, low grade, malignant, smooth muscle proliferation with an aneurysmal-like luminal space. No endoluminal or periadventitial invasive neoplastic component was present. The patient had no evidence of disease at 58-month follow-up. This is the first reported case of venous leiomyosarcoma in the foot. Furthermore, the intramural confinement of neoplastic growth is a unique observation. PMID- 7981800 TI - Clinical, quantitative assessment of first tarsometatarsal mobility in the sagittal plane and its relation to hallux valgus deformity. AB - Today, bunion surgery is still controversial. Considering that a bunion deformity in fact may be a result of multiple causes, the rationale of the currently applied techniques of surgical treatment has not been conclusively demonstrated. In view of the known hypermobility syndrome of the first ray that results in insufficient weightbearing beneath the first metatarsal head, the relationship between this syndrome and hallux valgus deformity has been investigated. The results suggest a direct relationship between painful hallux valgus deformity and hypermobility in extension of the first tarsometatarsal joint. A pathological mechanism of symptomatic hallux valgus is proposed that relates this pathology with primary weightbearing disturbances in the forefoot where angulation of the first metatarsophalangeal joint is one of the consequences. The alignment of the metatarsal heads within the sagittal plane seems to be a main concern in many hallux valgus deformities. As a consequence, treatment includes reestablishing stable sagittal alignment in addition to the horizontal reposition of the metatarsal over the sesamoid complex. As an example, first tarsometatarsal reorientation arthrodesis regulates the elasticity of the multiarticular first ray within the sagittal plane and may be the treatment of choice in many hallux valgus deformities. PMID- 7981802 TI - Cigarette smoking and nonunion after ankle arthrodesis. AB - The relative risk of nonunion in smokers versus nonsmokers after ankle arthrodesis was determined in a case control study. Twenty-two patients were matched to 22 controls by age, sex, surgeon, surgical technique, and preoperative diagnosis. Information on duration, amount, and past history of smoking was obtained for these 44 patients. Ten of the patients were actively smoking at the time of surgery compared with four of the controls. Six of the patients had no history of smoking and six had stopped smoking before surgery. Eleven of the controls had no history of cigarette smoking and 7 had stopped smoking before surgery. The relative risk of nonunion was increased 3.75 times for active smokers. When patients did not have any known risk factors for nonunion, the risk of nonunion for smokers was 16 times the risk of nonunion for nonsmokers. PMID- 7981801 TI - Avascular necrosis of the first metatarsal head: incidence in distal osteotomy combined with lateral soft tissue release. AB - The incidence of avascular necrosis of the metatarsal head following distal first metatarsal osteotomy combined with adductor tendon release has not been documented in a large series of patients. Of 82 consecutive procedures in 64 patients performed between 1986 and 1988, 42 patients (58 procedures) were available for clinical and radiographic examination. Average follow-up was 2.5 years (range 1.0-4.2 years). There were 35 L-shaped and 23 chevron osteotomies which were combined with a lateral soft tissue release that included adductor tenotomy. Preoperative hallux valgus angle averaged 25 degrees (range 15-40 degrees), and intermetatarsal angle averaged 12 degrees (range 5-24 degrees). Follow-up amount of correction averaged 13 degrees and 5 degrees, respectively. Eighty-four percent of patients were satisfied with their result. There was one case of avascular necrosis. The patient was asymptomatic at 4.2 years' follow-up, and the remaining patients included two with infections, one hallux varus, and no nonunions. PMID- 7981803 TI - The modified Robert Jones tendon transfer in cases of pes cavus and clawed hallux. AB - This is a retrospective study of the modified Robert Jones tendon transfer in 24 patients and 28 feet. The main indication for the procedure was to correct symptoms related to clawing of the hallux in seven patients, relieve pressure under the head of the first metatarsal in 13 patients, and treat for both symptoms in three patients. One patient had diffuse ache in the arch. Fifteen patients had idiopathic cavus feet, of whom five had associated spina bifida occulta. The remainder had a variety of different etiologies including cerebral palsy, head injury, brain abscess, and spinal cord tethering. Postoperative follow-up ranged from 7 months to 33 years with an average of 5 years and 6 months. The modified Robert Jones tendon transfer was shown to be effective in relieving symptoms related to clawing of the hallux in 90% of patients but was not reliable in curing pain under the first metatarsal head, with success in only 43% of patients. In three patients, pain under the metatarsal head was relieved initially but recurred by 18 months. Complications were frequent. Six patients developed pain under the tip of the hallux postoperatively. PMID- 7981804 TI - Epidemiology of sprains in the lateral ankle and foot. AB - The epidemiology of sprains in the lateral ankle and foot was investigated in a prospective study at the casualty ward at Hillerod County Hospital. During one year, 766 patients were registered. The overall sprain incidence was 7/1000 person-years. The incidence was highest for young males. After the age of 40 years, the incidence was higher for women than for men. Most sprains were sustained during sport, but, with increasing age, other activities became dominant. Sixty-one percent of the lesions were located around the lateral ankle, and 24% were located on the lateral midfoot. PMID- 7981805 TI - The influence of tibialis anterior muscle activity on rearfoot motion during walking. AB - The purpose of this study was to determine whether tibialis anterior muscle activity influences the rate of rearfoot motion during walking. Two-dimensional rearfoot motion was recorded from 23 feet. The feet were assigned to one of two experimental groups. Muscle activity was recorded from the tibialis anterior muscle using surface electrodes. The early pronators (N = 12) reached maximal pronation within the first 20% of the stance phase. The late pronators (N = 11) reached maximal pronation only after 40% of the stance phase. The results of a t test showed that there was a significant difference (P < .05) in the time to minimal tibialis anterior muscle activity between the two groups. These results indicate that tibialis anterior muscle activity can influence rearfoot motion during the stance phase of walking. A clinician should consider the muscular system when evaluating and designing a treatment program for patients with foot related problems. The results of this study also indicate that static nonweightbearing evaluations alone may not provide an accurate picture of the foot during walking. PMID- 7981806 TI - The use of magnetic resonance imaging in the diagnosis of stress fractures of the foot and ankle: four case reports. AB - Stress fractures result when bone is subjected to repeated loading which causes fatigue, cracking of the bone, and, eventually, a complete fracture. Stress fractures of the foot and ankle are common injuries affecting a broad range of the population, from the young to the elderly, the fitness enthusiast to the chronically debilitated. The diagnosis of stress fracture is not always obvious because radiographs are often negative, especially on initial presentation. In this report, we present four cases in which, after appropriate initial studies proved inconclusive, magnetic resonance imaging (MRI) was used to establish the diagnosis of stress fracture. We propose that MRI is a useful diagnostic modality in a select group of patients with suspected stress fractures of the foot and ankle. PMID- 7981807 TI - Magnetic resonance imaging in the diagnosis of localized pigmented villonodular synovitis of the ankle: a case report. AB - The use of magnetic resonance imaging (MRI) in pigmented villonodular synovitis (PVS) has been well described in the literature. MRI has been used predominantly with diffuse PVS lesions. We recently had a patient with an unusual case of localized PVS of the ankle with bone and cartilage destruction. Preoperative MRI was useful in the diagnosis of localized PVS and in the planning for surgery. MRI in a patient with this lesion had not been documented previously, but should be considered whenever PVS, either diffuse or localized PVS, is suspected. PMID- 7981808 TI - The diagnostic efficacy of magnetic resonance imaging and ultrasonography in Morton's neuroma: a radiological-surgical correlation. AB - All patients operated upon for Morton's neuroma during 1991 who were examined with both magnetic resonance imaging and ultrasonography were included in this prospective study. The object of the study was to evaluate the diagnostic value of these two modalities. The preoperative diagnosis was purely clinical. Histology confirmed surgical findings. A 0.3 T scanner was used for the magnetic resonance imaging, and a 7.5 MHz linear transducer was used for the ultrasonography. The study includes nine patients. Eight neuromas were found at surgery. Of these, only five were diagnosed with magnetic resonance imaging and three with ultrasonography. This indicates that false negative diagnoses are common. At present we find these modalities of little or no value, but, with improved equipment and experience, they may become valuable. PMID- 7981809 TI - "Comminuted fracture of the calcaneus associated with subluxation of the talus" and "Calcaneal fracture-dislocation with entrapment of the medial neurovascular bundle: a case report". PMID- 7981810 TI - Operative treatment of syndesmotic disruptions without use of a syndesmotic screw: a prospective clinical study. AB - A new protocol for the selected omission of transsyndesmotic fixation in Weber class C ankle fractures was prospectively evaluated in 21 consecutive patients. As proposed in a previous cadaveric study (J. Bone Joint Surg., 71A:1548-1555, 1989), the protocol suggested that transsyndesmotic fixation was not required if (1) rigid bimalleolar fracture fixation was achieved or (2) lateral without medial fixation was obtained (i.e., with accompanying deltoid tears) if the fibular fracture was within 4.5 cm of the joint. According to this protocol, only 3 of 21 patients (14%) required transsyndesmotic fixation. Ten of the patients who did not receive transsyndesmotic fixation underwent pronation-external rotation stress radiographs in a fashion analogous to the previous cadaveric study. At 1- to 3-year follow-up, no stress (N = 10) or static view (N = 18) widening of the mortise or syndesmosis was seen in any patient, which supports (with the above guidelines) a limited, rather than routine, use of supplemental transsyndesmotic fixation. Clinical results from this prospective study seem to substantiate previously proposed biomechanical guidelines for the selected omission of transsyndesmotic fixation. Given these guidelines, transsyndesmotic fixation was unnecessary in many cases and the need can be determined before surgery by assessing the integrity of the deltoid ligament and level of the fibular fracture. PMID- 7981811 TI - A biomechanical comparison of four fixation methods of first metatarsophalangeal joint arthrodesis. AB - A simulated metatarsophalangeal joint arthrodesis was performed on 18 pairs of cadaveric great toes. One toe of each pair was fixed with a 4.0-mm oblique AO cancellous screw. The contralateral toe was fixed with one of three techniques: (1) a miniplate placed dorsally; (2) a 4.5-mm Herbert cannulated screw placed from the metatarsal neck into the medullary canal of the proximal phalanx; or (3) a 3/32-inch Steinmann pin placed longitudinally. An oblique 0.045 Kirschner wire was added with each method. The specimens were tested to failure in dorsiflexion. The miniplate was significantly stronger than the AO screw in force to failure and initial stiffness. The Herbert cannulated screw was also significantly stronger in force to failure than the AO screw. There was no significant strength difference between the Steinmann pin and the AO screw. PMID- 7981812 TI - Anatomy of second muscular layer of the foot: considerations for tendon selection in transfer for Achilles and posterior tibial tendon reconstruction. AB - Controversy exists regarding tendon choice to substitute for a ruptured posterior tibial tendon. A similar debate about late Achilles tendon reconstruction also persists. To establish priorities and aid the surgeon's decision-making process, we studied 85 en bloc dissections of the second muscular layer of the sole. Muscular and tendinous interconnections were evaluated. Location and minimal donor deficit following harvest of the flexor digitorum longus make it the transfer of choice for posterior tibial tendon reconstruction. We suggest that relative strength, anatomic location, and available length of tendon make the flexor hallucis longus the superior choice for late Achilles tendon reconstruction. PMID- 7981813 TI - Arthroscopy of the subtalar joint. AB - The purpose of this study was to determine the position and relative safety of the anterior, posterior, and newly defined middle portals by measuring their distance from the neurovascular structures and tendons on the lateral side of the foot and ankle. Furthermore, this study demonstrates specific components of the posterior subtalar joint and arthroscopic access to each utilizing a technique that allows direct anatomic correlation. The 15 specimens were divided into three groups of five feet each, with one arthroscopic portal site and one instrumentation portal site per group. Group I used the anterior portal for the arthroscope and the posterior portal for the curette. Group II used the posterior portal for the arthroscope and the anterior portal for the curette. In group III, the arthroscope was inserted through the anterior portal and the curette through the middle portal. The sural nerve and small saphenous vein were at risk with posterior portal placement. The anterior portal presented a minor risk of injury to the dorsal intermediate cutaneous branch of the superficial peroneal nerve. The middle portal was without risk to surrounding structures. Group I provided the best access to the posterior facet of the subtalar joint. Group II provided excellent arthroscopic visualization of the posterior facet, but poor access for instrumentation via the anterior portal. Group III provided the best access to the sinus tarsi. No combination of portals allowed visualization or instrumentation of the middle or anterior facets. PMID- 7981814 TI - Osteoid osteoma of the neck of the talus: percutaneous, computed tomography guided technique for complete excision. AB - CT-guided core drill excision of talar neck osteoid osteomas, in addition to other locations, appears to be a promising alternative to standard surgical treatment. As in this report, the technique is minimally invasive, which allows for complete, accurate excision and early return to activity. PMID- 7981815 TI - Closed rupture of the flexor hallucis longus tendon in a long distance runner: report of a case and review of the literature. AB - A unique case report of rupture of the flexor hallucis longus tendon at the great toe metatarsal head level is reported in a well-trained marathon runner. The literature regarding interruptions of the flexor hallucis longus tendon is reviewed. There is an identifiable trend: Closed ruptures of the tendons when repaired, do not permit pull-through of the tendon, whereas open lacerations have some potential to restore this function. PMID- 7981816 TI - Detection of wooden foreign bodies in muscle tissue: experimental comparison of computed tomography, magnetic resonance imaging, and ultrasonography. AB - An experimental study was performed to compare computed tomography (CT), magnetic resonance imaging (MRI), and real-time, high resolution ultrasonography (US) for the detection of wooden foreign bodies in muscle tissue. Wooden splinters were prepared, measured for size, soaked in saline, and placed in porcine muscle distant from and adjacent to bone. The specimens were then examined using roentgenography, CT and MRI in planes parallel and perpendicular to the splinters, and US. The largest wooden foreign bodies (minimum smallest width = 10 mm) were easily detected by CT, MRI, and US. Almost all splinters of various sizes, small and large, soaked in saline for 5 months were easily detected by MRI. Smaller splinters (minimum smallest width = 1-4 mm) soaked for only 3 days and placed distant from bone were most easily detected by US; those soaked for 5 months were most easily detected by either US or MRI. The smaller splinters soaked for only 3 days and placed near bone were not reliably detected by any of the imaging methods; CT and MRI were both more sensitive than US in this situation. MRI scanning was more sensitive perpendicular than parallel to the long axis of the splinters. Therefore, either US or MRI may be the best initial imaging modality for evaluation of a suspected wooden foreign body, depending on availability of imaging method, chronicity of symptoms, and proximity to bone. PMID- 7981817 TI - The fracture table as a distraction mode in ankle arthroscopy. AB - Adequate distraction can be obtained in ankle arthroscopy by placing a Steinmann pin transversely in the calcaneus and using the fracture table in a hip or tibial nailing mode. A sterile traction bow is attached to the calcaneal pin and then to the traction crank apparatus of the fracture table. Gross traction is first applied through the leg in the usual manner and then fine traction tension may be increased or decreased intraoperatively through the traction crank. This method of using the fracture table is easy to perform and is familiar to the orthopaedist, as it is used in intramedullary nailing procedures. The primary advantage is that it allows for excellent exposure while avoiding the morbidity associated with a distraction pin through the distal tibia. PMID- 7981818 TI - Plantar dislocation of the metatarsophalangeal joint: case report. AB - Dislocations of lesser metatarsophalangeal joints are rare and are almost always dorsal hyperextension injuries. The patient reported sustained plantar dislocations of the second and third metatarsophalangeal joints in a motor vehicle accident; the mechanism of injury was hyperflexion. Closed reduction was not possible, and at the time of open reduction, the extensor digitorum longus and brevis tendons to the third toe were trapped beneath the plantar aspect of the third metatarsal head. Once the tendons were retracted dorsomedially, the joint was easily reduced. Fixation with a Kirschner wire was necessary because of joint instability. PMID- 7981819 TI - Bilateral stress fractures of the distal fibula in a 35-year-old woman. PMID- 7981820 TI - 6th International Symposium on High Performance Capillary Electrophoresis. San Diego, California, January 31-February 3, 1994. Part II. PMID- 7981822 TI - Control of the cultivation process of antithrombin III and its characterization by capillary electrophoresis. AB - The production by baby hamster kidney cells of recombinant antithrombin III (r-AT III), the main inhibitor of thrombin, factor Xa and other proteases of the clotting cascade, was monitored by capillary isotachophoresis using mixtures of continuous spacers. The results were compared with those obtained by capillary zone electrophoresis (CZE). The downstream process, which incorporated anion exchange and heparin affinity chromatography, was monitored by CZE under acidic conditions and voltage ramping. The purified product was characterized by its isoelectric point and molecular mass. Isoelectric points of the three major and three minor isoforms of AT III were evaluated by capillary isoelectric focusing using a pH range of 4-6 and various mobilization procedures. The molecular mass of AT III was investigated by capillary gel electrophoresis (CGE), applying removable dextran gels. Both parameters could be determined within 30 min using only one coated capillary. The results showed an excellent correspondence with those achieved with conventional slab gels. The affinity complex between AT III and thrombin could also be detected by CGE and the heparin dependence of the affinity reaction could be investigated. PMID- 7981821 TI - Evaluation of a novel hydrophilic derivatized capillary for protein analysis by capillary electrophoresis-electrospray mass spectrometry. AB - A new type of hydrophilic derivatized capillary has been used to enable the on line capillary electrophoresis separation and electrospray mass spectrometric detection of a mixture of proteins containing bovine cytochrome c, tuna cytochrome c and horse heart myoglobin. Less than 40 fmol of each compound were loaded into the capillary. Baseline resolution of components was achieved, as were accurate assignments of molecular masses. The hydrophilic derivatized capillaries were taken through extensive testing procedures to characterize their performance and capabilities for protein analysis. A mixture of six proteins (cytochrome c, ribonuclease A, alpha-chymotrypsinogen, myoglobin, carbonic anhydrase II and alpha-lactalbumin) in acetic acid-sodium acetate buffer was used to delineate the relationships between migration time and pH, along with migration time and buffer concentration for each protein. The variations in capillary efficiency as a function of pH and as a function of buffer concentration were also characterized for the same six proteins in the acetic acid-sodium acetate system. A pH of 4.8 was found to offer an excellent compromise between separation efficiency (up to 500,000 theoretical plates) and analysis time. Capillary efficiencies were also found to be very good when employing a Tris.HCl electrolyte adjusted to pH 4.8. Lastly, electropherogram reproducibility and capillary durability were examined with the finding that little deterioration of the capillary occurred over the course of 400 injections (200 h run time). This represents a notable improvement over previously documented derivatization procedures designed to reduce protein adsorption to fused-silica capillary walls. PMID- 7981823 TI - Affinity capillary electrophoresis applied to the studies of interactions of a member of heat shock protein family with an immunosuppressant. AB - The bioaffinity of receptor-ligand interactions is investigated by determining the binding constant (association constant or dissociation constant) of the resulting complex utilizing affinity capillary electrophoresis (ACE). The ACE binding assay was established with a potent immunosuppressant, deoxyspergualin (DSG), that binds specifically to Hsc70, a constitutive or cognate member of heat shock protein 70 (Hsp70) family. Quantitative determination of binding constants under different running buffer systems provide comparative results. The association constants for the interaction between Hsc70 protein and DSG were found to be 5.7 x 10(4) M-1 in a buffer with pH 6.95 and 6.3 x 10(4) M-1 in a buffer with pH 5.30 (or corresponding dissociation constants, 18 and 16 microM, respectively) based on Scatchard analyses. Binding of DSG to a synthetic peptide, SINPDEAVAYGAAVQAAILSGDK, one of the DSG-binding fragments found from tryptic digest of Hsc70 protein, provides further detailed information for the understanding of Hsc70 binding domain. The applicability of using coated capillaries was also evaluated for probing Hsc70-DSG interaction. PMID- 7981824 TI - Characterization of digoxigenin-labeled B-phycoerythrin by capillary electrophoresis with laser-induced fluorescence. Application to homogeneous digoxin immunoassay. AB - A laser-induced fluorescence (LIF) immunoassay technique based on capillary electrophoretic (CE) separation is demonstrated. The analysis of digoxin in serum at clinically useful concentration levels of 10(-9) to 10(-10) M is achieved using this technique. The chemistry presented here using digoxigenin-labeled B phycoerythrin was selected as a convenient model for the exploration of CE-LIF based immunoassays. The LIF system described here exhibits detection limits in the low 10(-11) M range for several common fluorophores. The data presented in this report are one of the first examples of nanomolar quantitative analysis in a human serum matrix by CE. PMID- 7981826 TI - Capillary electrophoresis of the scrapie prion protein from sheep brain. AB - Scrapie in sheep and goats causes a progressive, degenerative disease of the central nervous system and is the prototype of other transmissible spongiform encephalopathies (TSE) found in humans and in animals. In samples of TSE-affected brains, unique rod-shaped structures are found and are infectious. These rods are composed of a protease-resistant, post-translationally modified cellular protein (PrPsc) that has a molecular mass of ca. 27,000 on sodium dodecyl sulfate polyacrylamide gel electrophoresis. Laboratory tests used for the diagnosis of scrapie detect PrPsc. The overall concentration of PrPsc in tissues is low. The present methods to diagnose scrapie are lengthy, require relatively large quantities of starting material to detect PrPsc and lack sensitivity. We explored the use of free zone capillary electrophoresis and immunocomplex formation to detect PrPsc in the brain tissue of infected sheep. Brain tissue from both infected (as confirmed by histological and biological tests) and from normal animals was used to prepare the PrPsc. After treatment with proteinase K and non ionic detergents, PrPsc was solubilized and reacted with a rabbit antiserum specific for a peptide of the prion protein. Immunocomplex formation was observed for the samples from scrapie-infected brain but not for samples from normal brain. When a fluorescein-labeled goat anti-rabbit immunoglobulin was used as a second antibody, the detection of immunocomplex formation was enhanced both by the immunological technique and by using laser-induced fluorescence for detection. This same rabbit antiserum was used on immunoblot analysis. Three bands were observed for material from an infected sheep but none in preparations from brain material from normal sheep.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7981825 TI - High-performance capillary electrophoresis for characterization of hapten-protein conjugates used for production of antibodies against soyasaponin I. AB - Micellar electrokinetic capillary chromatography using sodium cholate as the micellar phase has been investigated for characterization of hapten-protein conjugates. Special focus has been placed on the hapten soyasaponin I which is a quantitatively dominating glycoside in seeds of several legumes including pea (Pisum sativum L.) and soybean [Glycine max (L.) Merr.]. Soyasaponin I has been isolated from pea and used as hapten for production of anti-saponin specific polyclonal antibodies. Soyasaponin I was coupled to Kunitz soybean trypsin inhibitor (KSTI) and bovine serum albumin. The degree of coupling was determined by high-performance capillary electrophoresis (HPCE). Capillaries dynamically coated with zwitterions were found to be efficient for reduction of interaction between the silica capillary surface and the proteins. The applicability of HPCE for determination of coupling density was confirmed by investigation of a model hapten (p-nitrophenyl-alpha-D-galactoside; PNPG) coupled to KSTI. The PNPG-KSTI conjugates were examined by both HPCE and by spectrophotometric determination of the PNPG density on KSTI. The HPCE method was shown to be efficient in studies of the formation of hapten-protein conjugates and to be more specific than alternative techniques applied for determination of coupling densities. PMID- 7981828 TI - Quantitative capillary gel electrophoresis assay of phosphorothioate oligonucleotides in pharmaceutical formulations. AB - Quantitative capillary gel electrophoresis (QCGE) has been developed for the accurate quantitation of a 21-mer phosphorothioate oligonucleotide, ISIS 2922, and its degradation products in an intravitreal formulation. The electrokinetic mode of injection employed by CGE necessitates formulation of the external reference standard in a sample matrix similar to that of the drug product and the use of an internal standard for improved accuracy and precision. The analytical method detailed in this paper has demonstrated the necessary accuracy, precision, linearity, range, selectivity and ruggedness for use in routine drug product analysis and stability monitoring of phosphorothioate oligonucleotides. PMID- 7981827 TI - Analysis of nucleotide pools in human lymphoma cells by capillary electrophoresis. AB - Capillary electrophoresis is applied to determine nucleotide pool levels in human Burkitt lymphoma cells. The analysis was performed on a 65 cm x 50 microns I.D. Ucon-coated column with on-column UV detector. The method requires only nanoliters of sample and a simple sample preparation procedure. Over 12 nucleotides were separated and quantitated with high resolution and reproducibility. The whole capillary electrophoretic separation time was only 35 min. These results demonstrate that capillary electrophoresis provides a useful and easy way to analyze nucleotide pools in cells. PMID- 7981829 TI - Capillary gel electrophoresis of oligonucleotides: prediction of migration times using base-specific migration coefficients. AB - Chemically synthesized oligodeoxyribonucleotides were subjected to capillary gel electrophoresis on three different polyacrylamide-based matrices. Analysis of about 1000 samples over a 1-year period showed that the gel matrix evolved with time resulting in shifting migration times, making it essential to use an internal standard. Cross-linked polyacrylamide matrices had the highest stability, allowing an average of 100 injections on the same capillary. Computer aided prediction of migration times was subsequently evaluated to confirm the size and base composition of oligonucleotides more accurately. A number of problems were noted when using this approach on a routine basis, such as insufficient stability of the gel matrices, effects of secondary structure on migration and insufficient differences in migration times for oligonucleotides containing > 50 bases. Capillary gel electrophoresis at pH 3.5 in replaceable gels showed that migration was mainly dependent on the charge per base ratio resulting in separations of significantly altered selectivity which complemented analyses under the commonly used basic pH conditions. PMID- 7981830 TI - High-speed and high-accuracy DNA sequencing by capillary gel electrophoresis in a simple, low cost instrument. Two-color peak-height encoded sequencing at 40 degrees C. AB - A low-cost DNA sequencer was constructed based on a single helium-neon laser. The two-color peak-height encoded sequencing protocol, based on the use of T7 DNA polymerase in a manganese buffer, was used to generate samples. Two termination reactions were performed. In the first, a TAMRA (applied Biosystems)-labeled primer was extended in the presence of ddATP and ddCTP. The amounts of dideoxynucleotides were adjusted to produce a 3:1 peak height ratio. Similarly, a ROX (Applied Biosystems)-labeled primer was extended in the presence of ddGTP and ddTTP; the amounts of dideoxynucleotides was adjusted to produce a 3:1 peak height ratio. The pooled fragments were separated on a 4% T LongRanger gel operated at 39 degrees C. Over 500 bases of sequence were generated in 50 min. PMID- 7981831 TI - Activation energy of single-stranded DNA moving through cross-linked polyacrylamide gels at 300 V/cm. Effect of temperature on sequencing rate in high electric-field capillary gel electrophoresis. AB - In DNA sequencing, single-stranded DNA fragments are separated by gel electrophoresis. This separation is based on a sieving mechanism where DNA fragments are retarded as they pass through pores in the gel. In this paper, we present the mobility of DNA sequencing fragments as a function of temperature; mobility is determined in 4% T LongRanger gels at an electric field of 300 V/cm. The temperature dependence is compared with the predictions of the biased reptation model. The model predicts that the fragment length for the onset of biased reptation with stretching increases with the square of temperature; the data show that the onset of biased reptation with stretching decreases with temperature. Biased reptation fails to model accurately the temperature dependence of mobility. We analyzed the data and extracted the activation energy for passage of sequencing fragments through the gel. For fragments containing less than ca. 200 bases, the activation energy increases linearly with the number of bases at a rate of 25 J/mol per base; for longer fragments, the activation energy increases at a rate of 6.5 J/mol per base. This transition in the activation energy presumably reflects a change in conformation of the DNA fragments; small fragments exist in a random coil configuration and larger fragments migrate in an elongated configuration. PMID- 7981832 TI - Analysis of polymerase chain reaction-product by capillary electrophoresis with laser-induced fluorescence detection and its application to the diagnosis of medium-chain acyl-coenzyme A dehydrogenase deficiency. AB - Capillary gel electrophoresis with laser-induced fluorescence (CGE-LIF) has been developed to detect polymerase chain reaction (PCR) amplified samples. LIF detection was performed using Thiazole Orange as the fluorescent intercalating dye. This method was ca. 100x as sensitive as that with UV detection. The highly sensitive CGE-LIF was applied to the detection of the most prevalent mutation (lysine329-to-glutamic acid substitution) in medium-chain acyl-coenzyme A dehydrogenase (MCAD) deficiency. The disorder, which shows an autosomal recessive inheritance, is known to be highly prevalent among Caucasian population and often mimics as Reye-like syndrome or sudden infant death. A DNA fragment containing the mutation site was PCR-amplified with two sets of allele specific oligonucleotide primers, followed by CGE-LIF. The mutant allele produced a 175 base pairs DNA fragment, which the normal allele generated a 202-base pairs DNA fragment. CGE-LIF clearly distinguished these PCR products, facilitating rapid diagnosis of MCAD deficiency. PMID- 7981833 TI - Analysis of DNA restriction fragments and polymerase chain reaction products by capillary electrophoresis. AB - Capillary electrophoresis (CE) is a new, high-resolution tool for the analysis of DNA restriction fragments and DNA amplified by the polymerase chain reaction (PCR). By combining many of the principles of traditional slab gel methods in a capillary format, it is possible to perform molecular size determinations of human and plant PCR amplification products and DNA restriction fragments. DNA restriction fragments and PCR products were analyzed by dynamic sieving electrophoresis (DSE) and capillary gel electrophoresis (CGE). As part of this study, sample preparation procedures, injection modes, and the use of molecular mass markers were evaluated. Optimum separations were performed using the uPage-3 (3% T, 3% C) CGE columns with UV detection at 260 nm. Membrane dialysis and ultrafiltration/centrifugation proved to be nearly equivalent methods of sample preparation. Reproducibility studies demonstrated that blunt-ended, non phosphorylated markers (specifically allele generated markers) provide the most accurate calibration for PCR product analysis. This study demonstrates that CE offers a high-speed, high-resolution analytical method for accurately determining molecular size and/or allelic type as compared with traditional methodologies. PMID- 7981834 TI - Determination of synthetic food dyes by capillary electrophoresis. AB - A method for the determination of synthetic tar dyes used as food additives using capillary electrophoresis with photodiode-array detection was investigated. The dyes Erythrosine (R-3), Phloxine (R-104), Rose Bengal (R-105), Acid Red (R-106), Amaranth (R-2), New Coccine (R-102) and Allura Red AC (R-40) were separated on a capillary column (50 cm x 75 microns I.D.) and identified from the absorbance spectra of each peak. The electrophoresis buffer used was a mixture of 25 mM sodium phosphate buffer and 25 mM sodium borate buffer (1:1) (pH 8.0) containing 10 mM sodium dodecyl sulfate (SDS). Substitution of beta-cyclodextrin for SDS in the electrolyte buffer was effective for the separation of R-2 and R-102. This modified method could be employed as an additional assay method for these two dyes. PMID- 7981835 TI - Determination of pharmaceuticals and related impurities by capillary electrophoresis. AB - In the first part of this work, the use of capillary electrophoresis (CE) for the separation of two groups of pharmaceuticals, namely a metabolite of tamoxifen and a basic drug substance, DS1 was investigated. The effects of pH and types of modifiers, e.g. surfactant, bile salt, gamma-cyclodextrin and hydroxypropyl-beta cyclodextrin on selectivity, separation and peak shape were studied. Besides achieving complete separation of the compounds, the CE system was capable of providing separation with significant improvements in overall peak shape of the compounds compared with HPLC. In the case of the basic drug substance DS1, validation of the CE system developed in terms of linearity, selectivity, sensitivity and reproducibility was satisfactorily performed. At the same time, a study of the sample solvent matrix effects on the separation of this group of compounds was examined. The system was successfully applied to the analysis of laboratory-synthesized samples. Good correlation was observed between CE and HPLC, although higher efficiency and faster speed of separation were obtained using the CE system developed. For the tamoxifen metabolite, special emphasis was placed on the use of CE for the separation of the pair of isomers. This was readily achieved through the introduction of gamma-cyclodextrin in the electrolyte. Resolution of at least 1.5 was obtained for the isomers using the CE method. PMID- 7981836 TI - Analysis of structural specificity in antibody-antigen reactions by capillary electrophoresis with laser-induced fluorescence detection. AB - A rapid and simple procedure for screening antibodies for binding to an antigen is proposed. A fluorescent hapten-dye conjugate was prepared by labeling the amino moiety of the hapten with a commercially available reactive cyanine dye, Cy5 (excitation maximum: 650 nm, emission maximum: 670 nm). A fixed amount of the Cy5-hapten was titrated with serial dilution of the antibody. Each of the titration mixture was analyzed by capillary electrophoresis (25 cm x 20 microns column) monitored by laser-induced fluorescence (laser: 10 mW helium-neon, 632.8 nm). Free and antibody-bound Cy5-hapten were analyzed simultaneously on the electropherogram. Competitive immunoassay of hapten was demonstrated with low-end sensitivity of 5.10(-8) M, about 10x more sensitive than the present drug screening methods. Using morphine as an example, the screening of various antibodies (from different vendors) and cross-reactivity of morphine analogues using the present procedure will be discussed. PMID- 7981838 TI - Gradient elution in micellar liquid chromatography. II. Organic modifier gradients. AB - The application of organic modifier gradients in micellar liquid chromatography (MLC) is discussed. The equation derived by Snyder and co-workers describing gradient elution in hydro-organic reversed-phase LC was verified for organic solvent gradients in the presence of micelles. It is also demonstrated that the use of these gradients require little re-equilibration time due to the limited range of organic modifier concentration used in the gradient. This would result in shorter analysis time. Lastly, a practical application of the use of propanol and acetonitrile gradients in MLC is described. PMID- 7981837 TI - Gradient elution in micellar liquid chromatography. I. Micelle concentration gradient. AB - Gradient elution in micellar liquid chromatography (MLC) is discussed. On the basis of the gradient elution theory, first developed by Snyder, equations were derived for the prediction of gradient retention times in micelle concentration gradient from isocratic data. Likewise, partition coefficients into micelles and stationary phase, and subsequently isocratic retention at different micelle concentrations can be estimated from two gradient runs. However, more studies need to be done to achieve better agreement between isocratic and gradient data. The equations will be useful for efficient development of practical separations by MLC. PMID- 7981839 TI - Gas chromatographic retention behaviour of polychlorinated naphthalenes on non polar, polarizable, polar and smectic capillary columns. AB - Six commercially available gas chromatography columns were investigated for performance in separating polychlorinated naphthalenes (PCNs). Retention behaviour on the investigated phases is compared and retention data for 40 congeners on a 5% phenyl-methylpolysiloxane column is reported. For all columns, except the octylmethylpolysiloxane and the smectic, a relation between substitution pattern and retention was found, where substitution in adjacent positions as well as alpha-substitution increase the retention time. A mathematical model based on these findings was developed and used to predict the relative retention of all congeners from di- up to octachloronaphthalene, on a 5% phenyl-methylpolysiloxane column. PMID- 7981840 TI - Concentrations of Lp(a) in black and white young adults: relations to risk factors for cardiovascular disease. AB - The purpose of this report is to compare the distribution of total lipoprotein(a) [Lp(a)] mass in a population-based sample of blacks and whites, and to investigate the association of Lp(a) with other cardiovascular risk factors. A cross-sectional study design was used. Black and white men and women (n = 4125), aged 23-35 from the Coronary Artery Risk Development in Young Adults Study had the following data collected: Lp(a), lipids and lipoproteins, other metabolic parameters, anthropometry, physical activity, dietary intake, cigarette use, and alcohol use. Blacks had concentrations of Lp(a) approximately three-fold higher than whites. Medians were: black men 21.5 mg/dL, black women 23.9 mg/dL, white men 6.1 mg/dL, and white women 6.4 mg/dL. Lp(a) concentrations were higher in women than in men. Lp(a) was not consistently associated with smoking, alcohol consumption, physical activity, dietary fat, or obesity. In stepwise regression analyses in both blacks and whites, Lp(a) was consistently associated with low density lipoprotein (LDL) cholesterol, fibrinogen, and apoB; regression models explained about 7% of the variance in Lp(a). In whites, Lp(a) tended to be higher in those with a positive family history of myocardial infarction. The large differences in Lp(a) between blacks and whites, and the absence of association with many other variables are consistent with previous suggestions that Lp(a) concentration is in large part genetically determined. The association of Lp(a) with LDL and fibrinogen, two strong risk factors for cardiovascular disease (CVD), could represent part of the mechanism of the CVD risk associated with Lp(a) in other studies. Longitudinal data are needed to determine the extent to which Lp(a) will independently predict disease, especially in diverse ethnic groups. PMID- 7981842 TI - Lipoprotein(a) and risks of cardiovascular disease. PMID- 7981841 TI - Lipoprotein(a) as a correlate of stroke and transient ischemic attack prevalence in a biracial cohort: the ARIC Study. Atherosclerosis Risk in Communities. AB - Although both mean lipoprotein(a) [Lp(a)] concentration and national stroke prevalence estimates are consistently higher in American blacks than in whites, no information exists on the relationship of Lp(a) and stroke prevalence in African-Americans. Associations of Lp(a) with stroke or transient ischemic attack (TIA) are addressed in this report for 15,160 participants--4160 blacks and 11,000 whites--in the Atherosclerosis Risk in Communities (ARIC) Study. Lp(a) was measured in ARIC as its total protein component by double-antibody enzyme-linked immunosorbent assay (ELISA) for apo(a) detection. Self-reported stroke/TIA history was assessed as part of a standardized questionnaire, and resulted in age adjusted stroke/TIA prevalences of 3.0% in blacks (n = 120) and 2.0% in whites (n = 222). Overall, mean Lp(a) protein levels were markedly higher for blacks than for whites (160.5 versus 81.6 micrograms/mL, respectively), and were statistically significantly higher among individuals reporting stroke/TIA history for both races (191.3 versus 159.6 micrograms/mL in blacks; 100.6 versus 81.2 micrograms/mL in whites). Multivariable logistic regression analysis for the association of Lp(a) protein with stroke/TIA status yielded a prevalence odds ratio (OR) (95% confidence intervals) of 1.17 (1.05, 1.30) overall (based on one standard deviation difference, 108.2 micrograms/mL, in Lp[a] protein). Race specific ORs, after adjustment for the same covariates, were equivalent for blacks [OR = 1.17 (0.99, 1.39)] and whites [OR = 1.19 (1.04, 1.36)]. These data suggest that Lp(a) is an independent risk factor for stroke/TIA in both blacks and whites, and that the relative risk of stroke/TIA associated with Lp(a) protein does not vary by race.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7981843 TI - Lifestyle and glucose tolerance: a cross-sectional study of Japanese men. AB - The relationship of smoking, alcohol use, body mass index, and physical activity to glucose tolerance was studied in 2407 male self-defense officials aged 49-56 years who received a health examination before retirement at the Self-Defense Forces Fukuoka Hospital from October 1986 to December 1990. Body mass index (BMI) was significantly, positively related to impaired glucose tolerance (IGT) and noninsulin-dependent diabetes mellitus (NIDDM); after adjustment for rank of the Self-Defense Forces, smoking, alcohol use, prior diagnosis of diabetes mellitus, and parental history of the disease, odds ratios (ORs) of IGT and NIDDM for the highest (> or = 25.5 kg/m2) versus lowest (< 21.6 kg/m2) quintile of BMI were 4.2 [95% confidence interval (CI) 2.6-6.8] and 4.6 (95% CI 2.3-9.3), respectively. Cigarette smoking was weakly, positively associated with IGT and strongly so with NIDDM; adjusted ORs of IGT and NIDDM for 800 cigarette-years or more versus never smoking were 1.6 (95% CI 1.1-2.5) and 4.1 (95% CI 1.8-9.3), respectively. The prevalence of IGT and NIDDM tended to be decreased among men with high physical activity as measured by the time spent for vigorous exercise in leisure time. There was virtually no association between alcohol consumption and either IGT or NIDDM. The findings suggest that obesity and cigarette smoking are important factors in the development of glucose intolerance in middle-aged Japanese men. PMID- 7981844 TI - Association between fibrinogen and other risk factors for cardiovascular disease in men and women. Results from the Goteborg MONICA survey 1985. AB - Plasma fibrinogen and its association to other risk factors for cardiovascular disease was investigated in a random sample of 691 men and 739 women, aged 25 to 64 years, participating in the Goteborg MONICA survey. In both genders univariate analyses revealed significantly positive correlations between plasma fibrinogen and age, body mass index (BMI), waist/hip ratio (WHR), systolic blood pressure, serum cholesterol and triglycerides and a negative correlation to high-density lipoprotein (HDL) cholesterol; however, the degree of relationship varied between men and women. Smoking was significantly correlated to fibrinogen (P < 0.001) in men, whereas the association was weaker in women. Multivariate analysis showed that plasma fibrinogen in both genders was significantly correlated to age, smoking, and BMI. The influence of smoking was stronger in men and BMI was stronger in women. Furthermore, the association of fibrinogen to HDL cholesterol was significant only in men and to triglycerides only in women. Plasma fibrinogen was significantly related to gender; when all other significant variables were taken into account, women had higher fibrinogen levels than men. PMID- 7981845 TI - Jogging or walking--comparison of health effects. AB - The present study compared the different health effects of 6 months' endurance training at two exercise intensities. Seventy-five nonsmoking, sedentary men were randomly assigned to either a home-based, unsupervised exercise program of 4 x 30 min/wk jogging at an intensity of 75% VO2max (n = 28), or of 6 x 30 min/wk walking at an intensity of 50% VO2max (n = 28), or to an inactive control group (n = 19). Exercise adherence and injuries related to exercise training as well as changes in endurance capacity, body fat, and serum lipids were assessed. After 6 months, joggers and walkers showed a similar increase in VO2max as measured by a maximal bicycle ergometer test (2.9 +/- 4.1 ml/kg min, P < 0.01 and 2.5 +/- 5.7 ml/kg min, P < 0.5, respectively). There were no significant changes in blood lipids in either group, although results revealed a significant association between the amount of training (i.e., kilometers exercised) and the increase in high-density lipoprotein-cholesterol (HDL-C) in joggers (Pearson's r = 0.42, P < 0.05). In walkers, a significant association between the amount of exercise and the decrease in sum of skinfolds and the waist-hip ratio was observed (Pearson's r = -0.48 and -0.45, P < 0.05 for both). The adherence rate was similar for both training groups with respect to the prescribed intervention goal with an average of 90 +/- 41 min/wk (joggers) and 121 +/- 72 min/wk (walkers) spent on endurance training.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7981846 TI - Host factors and environmental determinants associated with skin test reactivity and eosinophilia in a community-based population study. AB - We examined the relationship of host factors (age, gender) and environmental determinants (smoking status, area of residence) to indicators of allergy (skin test reactivity and eosinophil count) in a random population sample in the Netherlands. Positive skin test reactivity was associated with age (decreasing with increasing age), with male gender (versus female gender), and with urban residence (versus rural residence). Positive skin test reactivity was not associated with smoking. Elevated eosinophil counts were associated with male gender (versus female gender), with urban residence (versus rural residence), and with current smoking (versus never smoking). Elevated eosinophil counts were not clearly associated with age (if adjusted for the age-related effects of skin test reactivity). Additionally, this study specifically demonstrates that skin test reactivity increases with increasing eosinophil count and vice versa, indicating that the two traits are interrelated. Furthermore, this interrelationship was demonstrated to be age-dependent (decreasing with increasing age). PMID- 7981847 TI - Recall bias in disease status associated with perceived exposure to hazardous substances. AB - Recall bias was assessed in a study of cancers reported by persons living in a community with a hazardous waste treatment facility (A) and a control community (B). The self-reported cancers were verified against medical records and pathology reports. Of the 56 cancer cases reported, 43 were in community A and 13 were in community B. The difference in incorrect reporting of neoplasms between community A and community B was 12% for neoplasms and 23% for malignancies. Before verification, there was a borderline significant association (P = 0.049) between living in community A and all self-reported cancers [odds ratio (OR) 1.88, 95% confidence interval 0.99-3.57]. The verified data showed that ORs decreased with the increasing precision of diagnosis. The effect of misclassification on the OR was an inflation by 15% for neoplasms and by 31% for malignancies. The results demonstrate the importance of verifying reported cases of disease, even a disease as well defined as cancer. PMID- 7981848 TI - Comparison of respondents and nonrespondents in an osteoporosis study. AB - We attempted to enroll an age-stratified random sample of Rochester, Minnesota women > or = 30 years of age in a population-based prospective study of the determinants of bone loss. Using the resources of the Rochester Epidemiology Project, 541 women were contacted and 305 agreed to participate. Of 236 nonrespondents, 38 were ineligible and 198 refused to participate resulting in a 61% response rate for eligible subjects. We reviewed community medical records for respondents and nonrespondents (including ineligibles) to determine whether the two groups differed with regard to variables that might be important in osteoporosis research. There was little difference between respondents and nonrespondents for a history of cigarette smoking, hyperthyroidism, thyroidectomy, or age-related fractures. Respondents survived better, were less likely to be obese or have renal failure, and more likely to have had an oophorectomy and consume alcohol (P < 0.01). These data suggest that nonrespondents were less healthy than respondents. PMID- 7981849 TI - Eating patterns of community-dwelling older adults: the Cardiovascular Health Study. AB - We analyzed eating patterns of 4643 adults (1988 men and 2655 women) aged 65 years and older at the time of their enrollment in the Cardiovascular Health Study. Diet was assessed with a qualitative, picture-sort food frequency questionnaire along with supplemental questions on other eating pattern variables. Consumption of high fat foods and low fiber foods was more frequent in older participants, men, minorities, and persons with body mass index > or = 30 kg/m2 and less common among persons who reported following self-prescribed or medically prescribed special diets. Few associations of consumption of specific food groups with disease status were identified. Participants with coronary heart disease, diabetes, hypertension, and cardiovascular disease were significantly more likely to report following a special diet and using low-calorie or low sodium food products, however. Although the percentage of participants with prevalent disease who reported following special diets was relatively low from a clinical perspective, it was sufficiently high to suggest that controlling for dietary modifications may be important when attempting to identify associations of diet with prevalent disease in older populations. PMID- 7981850 TI - Premature menopause and low back pain. A population-based study. AB - The association between premature menopause and low back pain was examined among 5325 women surveyed in the second National Health and Nutrition Examination survey. Nearly 49% of the women were postmenopausal. In a multiple logistic regression model that included age, postmenopausal women were approximately twice as likely to report low back pain compared to premenopausal women (odds ratio = 2.1; 95% confidence interval: 1.4-3.0). Among postmenopausal women, significant positive trends in low back pain were observed with decreasing age at menopause (P = 0.005) and increasing years since menopause (P = 0.004). The prevalence odds ratio for women who had their menopause before the age of 30 was 3.2 (1.8-5.4); and for women who had their menopause for 15 or more years the odds ratio was 3.0 (1.7-5.3). These findings suggest that premature menopause is associated with low back pain. Further studies appear warranted to confirm these findings, assess possible explanations, and examine the circumstances in which premature menopause occurs. PMID- 7981851 TI - Cocaine, marijuana, fertility, and coital rates. PMID- 7981852 TI - The undulated mouse and the development of the vertebral column. Is there a human PAX-1 homologue? AB - The mouse is a very useful system for the analysis of vertebral column development, particularly as a model for human skeletal diseases. A large number of mutant mouse strains exist with specific inherited skeletal defects. Undulated (un) is one of these mutants showing abnormalities of the vertebral bodies and intervertebral discs. The gene responsible for un has been identified as the Pax 1 gene, a member of the Pax-gene family. A human disease homologue to un is not known so far. In order to facilitate identification of a potential human PAX-1 disease, an overview is given describing what is currently known about the pathological and molecular analysis of un. It is hoped that this will help medical geneticists and dysmorphologists to identify a potential human disease, which corresponds to a mutation in the PAX-1 gene. PMID- 7981853 TI - The Mayer-Rokitansky-Kuster-Hauser (MRKH) syndrome without and with associated features: two separate entities? AB - A multidisciplinary study was conducted on a total of 100 women with congenital absence of vagina and uterus, the Mayer-Rokitansky-Kuster-Hauser (MRKH) syndrome. It was possible to analyse whether the MRKH syndrome can be considered as a single clinical entity or whether two or more syndromes lie behind the title 'the MRKH syndrome'. Complete gynaecological and laparoscopic data were available on all of the patients. The patients were divided into two groups on the basis of the laparoscopic data: a typical and an atypical form of the MRKH syndrome. We performed various diagnostic investigations to establish whether there were any associated congenital anomalies. These tests included general physical examination, radiographs of the vertebral column, the upper extremities and intravenous urography (IVU), and general otorhinolaryngological and ossicular chain examinations. Associated anomalies were most common in the group with the atypical form of the MRKH syndrome. These findings suggest that there might be two different syndromes in this patient group, namely an isolated form of congenital agenesis of the vagina and uterus and a more generalized condition, in which agenesis of the vagina and uterus is a major and perhaps even obligatory characteristic. The term MRKH syndrome should no longer be used for the atypical group. A suggestion has been made to call this type the GRES [genital (G), renal (R), ear (E), skeletal (S)] syndrome. PMID- 7981854 TI - Radial ray defects, renal ectopia, duodenal atresia and hydrocephalus: the extended spectrum for Fanconi anaemia. AB - We present two families with a striking concordance of multiple anomalies. These include duodenal and other bowel atresia, radial ray defects especially absent or vestigial thumb, renal ectopia and hydrocephalus. The presence of diagnostically raised sensitivity to mitomycin C in the first family has confirmed Fanconi anaemia. This has further increased the spectrum of abnormalities in Fanconi anaemia and highlights the importance of mitomycin C analysis if elements of this spectrum are encountered. PMID- 7981855 TI - Further delineation of the ear, patella, short stature syndrome (Meier-Gorlin syndrome). AB - Two daughters of phenotypically normal parents are described with severe proportional dwarfism with microcephaly, peculiar craniofacial anomalies, microtia, absent patellae, joint hyperextensibility, and other anomalies. Intrafamilial variability is minimal. This combination of anomalies has many similarities to the six cases previously described with the Ear, Patellae, Short stature syndrome (Meier-Gorlin syndrome), which is distinguished by the triad of microtia, absent patellae and growth retardation. Autosomal recessive inheritance is strongly suggested by the presence of two pairs of affected siblings and the equal sex ratio. PMID- 7981857 TI - Characteristic facies in type B brachydactyly? AB - We report a family with type B brachydactyly. The distinctive facial appearance of those affected raises the possibility of an association. PMID- 7981856 TI - A distinct autosomal dominant craniosynostosis-brachydactyly syndrome. AB - We report a family with an autosomal dominantly inherited craniosynostosis. Five affected individuals have been identified with a variable clinical picture of premature coronal sutural synostosis accompanied by a mild midfacial hypoplasia and hypertelorism, downslanting external palpebral fissures, beaking of the nose and brachydactyly. This pedigree appears to represent a distinct craniosynostosis entity. PMID- 7981858 TI - Two isolated cases with symmetrically absent hands and feet. AB - We describe two unrelated boys with similar bilateral terminal transverse defects of the upper and lower limbs without other anomalies. Review of the literature did not reveal another report of this distinctive type of malformation. PMID- 7981859 TI - Rigid mask-like face, ear anomalies, deafness, preaxial polydactyly and toe malformations in a patient with normal intelligence: a new entity? AB - We describe a patient with deafness, normal intellect and a unique phenotype characterized by a rigid mask-like face, narrow, upslanting palpebral fissures, flat malar bones, thick lower lip, malformed auricles, preaxial polydactyly with triphalangeal thumbs, syn-ectrodactyly of toes and first degree hypospadias. PMID- 7981860 TI - Anterior segment anomalies of the eye, clefting and skeletal abnormalities in two sibs of consanguineous parents: Michels syndrome or new syndrome? AB - We report two sibs of consanguineous parents with multiple congenital abnormalities which include prenatal and postnatal growth retardation, anterior segment defects of the eye, arachnodactyly with other skeletal abnormalities, congenital heart disease and early lethality. We think this constellation of anomalies may represent a previously undescribed syndrome. There are some similarities to Michels syndrome from which it should be differentiated. PMID- 7981861 TI - Oral-facial-digital syndrome II. Transitional type between Mohr and Majewski syndrome: report of a new case with congenital stenosis of the trachea. AB - We present a female patient with laryngeal anomalies, tracheostenosis and pre- and postaxial polydactyly. Bilateral duplication of the hallux, polydactyly of hands, growth retardation and conductive hearing defect are consistent with oral facial-digital (OFD) type II syndrome. Three similar cases of OFD syndrome with hypoplasia of the larynx, epiglottis and/or trachea without tibial dysplasia have been previously reported by Silengo and Temtamy and McKusick. The present patient adds one more case to this group of variants of OFD syndrome. We believe that those cases may be considered to form a separate subentity of OFD syndromes although overlapping features within the different subtypes make a precise classification very difficult. PMID- 7981862 TI - Taurodontism and disproportionate short stature. AB - A 13-year-old boy with taurodontism and disproportionate short stature is described. Parental consanguinity suggests the possibility of an autosomal recessive mode of inheritance. PMID- 7981863 TI - Microphthalmia and distal limb abnormalities in a child of consanguineous parents. AB - We report a child of consanguineous parents with microphthalmia and distal limb abnormalities. The association between eye and distal limb abnormalities have been reported previously. However, the eye involvement in the child in this report is less severe than the previously reported cases. PMID- 7981864 TI - Bilateral brachial amelia with facial clefts and holoprosencephaly. PMID- 7981865 TI - Anencephaly with spinal dysraphism, cleft lip and palate and limb reduction defects. AB - We report three unrelated fetuses presenting with anencephaly, spinal dysraphism, cleft lip and palate and limb reduction defects. Review of the literature suggests that this association may be more commonly found than previously recognized and may indicate severe disturbance in early embryogenesis. PMID- 7981866 TI - The SP1 antigen in subplate neurons of the developing cat cortex is an immunoglobulin-like molecule. AB - Monoclonal antibody subplate-1 (mAb SP1) specifically stains somata, dendrites and axons of spiny inverted pyramidal neurons in the subplate zone in the early postnatal kitten neocortex. The SP1 antigen has been previously identified as a cytosolic protein of apparent molecular weight 56 kDa. We have now employed immune-affinity chromatography to further characterize this antigen. An antigen with SP1-like immunoreactivity (ir) is present in various organs, and is particularly enriched in blood plasma. Exsanguination of the organs prior to protein extraction reduces the SP1-ir band dramatically, indicative of a blood borne molecule. The 56 kDa SP1-ir antigen was purified from plasma by affinity chromatography and subjected to Edman degradation. The first 20 N-terminal amino acids show 80% homology to the N-terminus of immunoglobulin heavy chain of man, the mouse and the dog. If the 56 kDa SP1-ir antigen in plasma is an immunoglobulin, and if an immunoglobulin-like molecule is present in the subplate, then antisera against cat immunoglobulins should stain subplate neurons. A polyclonal antiserum against cat IgG intensely stains the somata and dendrites of subplate neurons. On protein blots, this antiserum recognizes the 56 kDa band, and an additional band of approximately 27 kDa, corresponding in size to immunoglobulin light chains. Preabsorbing mAb SP1 with cat immunoglobulin G abolishes the immunoreactivity in sections of kitten cortex. Further, it dramatically reduces the reactivity on protein blots. The results suggest that the 56 kDa SP1-ir antigen in cortical subplate neurons belongs to the immunoglobulin superfamily. PMID- 7981867 TI - The NMDA receptor antagonist CPP suppresses long-term potentiation in the rat hippocampal-accumbens pathway in vivo. AB - Excitation of afferent fibres originating in the ventral subiculum of the hippocampus through stimulation of the fimbria elicits field potentials in the nucleus accumbens. When recorded in the dorsomedial aspect of the nucleus accumbens, the evoked field responses consisted of an early, negative-going component (N1) with a peak latency of 8-10 ms, followed by a second negative going peak (N2) with a latency of 22-24 ms. The N1 response reflects monosynaptic activation of nucleus accumbens neurons; the N2 component appears to be polysynaptic in origin. In control rats, high-frequency stimulation of the fimbria (three trains at 250 Hz, 250 ms, delivered at 50 min intervals) resulted in a long-lasting potentiation of both the N1 and N2 components. The magnitude of potentiation exhibited by the polysynaptic N2 response was typically greater than that of the monosynaptically evoked N1 response. Following delivery of the first train, the amplitude of the N1 and N2 components was increased by approximately 20 and 50% respectively. Administration of the competitive N-methyl-D-aspartate (NMDA) receptor antagonist 3-[(+-)-2-carboxypiperazin-4-yl]-propyl-1-phosphonic acid (CPP, 10 mg/kg i.p.) had no significant effects on the evoked nucleus accumbens responses. High-frequency stimulation failed to produce a significant increase in the amplitude of either the N1 or the N2 response when delivered 45 60 min after CPP administration. To test whether the suppressant effects of CPP were time-dependent, two further high-frequency trains were applied 90 and 180 min after administration of the drug.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7981868 TI - The entorhinal cortex and a delayed non-matching-to-place task in mice: emphasis on preoperative training and presentation procedure. AB - This study examined the effects of ibotenate lesions of the entorhinal cortex (EC) on performance of a spatial recognition memory task, the delayed non matching-to-place task (DNMTP), varying in level of difficulty according to the number of interpolated arm visits between sample-place presentation and subsequent recognition in mice. Results of experiment 1, designed to test the rate of acquisition of the task, showed that experimental animals were impaired in the basic non-matching task. However, with further training they were able to learn the task. Impairments were also observed when the amount of interpolating information inserted was gradually increased, and then all problem difficulties were pseudorandomly tested. There was no measurable recovery of function over time when the animals were retested on the task approximately 1 month later. Experiment 2 showed that the animals that received extensive training on the task prior to lesions of the EC were only transiently impaired in the DNMTP task. These data suggest that the EC plays an important role in acquisition rather than retention of the spatial recognition memory task. PMID- 7981869 TI - Developmental loss of GABA- and glycine-induced depolarization and Ca2+ transients in embryonic rat dorsal horn neurons in culture. AB - More than 90% of dorsal horn neurons from embryonic day 15-16 rats responded to the inhibitory amino acids GABA and glycine by a transient elevation of intracellular Ca2+ concentration ([Ca2+]i) when maintained in culture for < 1 week. This [Ca2+]i response has previously been shown to be due to depolarization and subsequent Ca2+ entry through voltage-gated Ca2+ channels following activation of bicuculline-sensitive GABAA receptors and strychnine-sensitive glycine receptors. Both the number of cells responding to GABA and glycine and the amplitude of the [Ca2+]i response diminished over time in culture. By 30 days in culture, none of the cells responded to GABA, muscimol or glycine by elevation of [Ca2+]i. The loss of the [Ca2+]i response was not due to a change in the abundance or the properties of voltage-gated Ca2+ channels, since over the same period of time dorsal horn neurons showed a large increase in the amplitude of the [Ca2+]i transient in response to 30 mM K+. Nor was the loss of the [Ca2+]i response due to a loss of GABA and glycine receptors. Instead, the decrease in the [Ca2+]i response over time paralleled a similar change in the electrophysiological responses. More than 90% of the neurons tested were depolarized in response to inhibitory amino acids during the first week in culture. After 30 days, all neurons tested responded to GABA and glycine with a hyperpolarization. These observations add support to the suggestion that GABA and glycine may excite dorsal horn neurons early in development and play a role in postmitotic differentiation. PMID- 7981870 TI - Pharmacology and biophysical properties of alpha 7 and alpha 7-alpha 8 alpha bungarotoxin receptor subtypes immunopurified from the chick optic lobe. AB - Two chick optic lobe alpha-bungarotoxin receptor subtypes (alpha 7 and alpha 7 alpha 8) were immunopurified using polyclonal antibodies raised against synthetic peptides of chick alpha 7 and alpha 8 alpha-bungarotoxin receptor subunits. The alpha 7 subtype contained the M(r) 57,000 alpha 7 subunit, and represented 60-70% of the alpha-bungarotoxin receptors; the alpha 7-alpha 8 subtype contained the M(r) 57,000 alpha 7 and alpha 8 subunits, and represented only 20-25% of the receptors. Both subtypes also had an additional M(r) 52,000 subunit. The affinity of these subtypes for alpha-bungarotoxin as well as antagonists was similar. However, the alpha 7-alpha 8 subtype displayed consistently higher affinities for agonists. When reconstituted in planar lipid bilayers, the alpha 7-alpha 8 subtype displayed several conductance states of 10-50 pS; the alpha 7 subtype had only one conductance state of 45 pS. The alpha 7-alpha 8 subtype was activated by lower agonist concentrations than the alpha 7 subtype. When expressed in Xenopus oocytes, the alpha 8 subunit formed functional homomeric receptors that desensitized rapidly. These channels were blocked by alpha-bungarotoxin and displayed a higher affinity for agonists than the alpha 7 homomeric receptor. Taken together, these data indicate that at least two alpha-bungarotoxin subtypes are present in the chick optic lobe. They operate as ligand-gated channels and display different agonist sensitivities and kinetics/conductance properties. PMID- 7981871 TI - Corticosteroid receptor antagonists are amnestic for passive avoidance learning in day-old chicks. AB - Glucocorticoids can modulate behavioural processes and neural plasticity. They are released during learning situations and can trigger neural actions through binding to brain receptors. We hypothesized that a glucocorticoid action could play a critical role in the mechanisms involved in long-term memory formation. In order to test this hypothesis, chicks were trained on a passive avoidance learning task and given bilateral intracerebral injections of selective mineralocorticoid (RU-28318) or glucocorticoid (RU-38486) receptor antagonists. The results showed that both antagonists alter information processing when injected prior to the training session. Possible state-dependent effects were discharged. Further experiments evaluating possible effects of the antagonists on concomitant aspects of the learning situation (such as novelty reaction and pecking pattern) indicated that, as opposed to the glucocorticoid receptor antagonist, the mineralocorticoid antagonist altered the birds' reactivity to non specific aspects of the training task. These results suggest that the two types of intracellular corticosteroid receptors could be mediating different aspects of the information processing and storage involved in avoidance learning. In addition, this study points out that passive avoidance learning in the chick could be a good model to investigate the biochemical mechanisms involved in corticosteroid actions on learning-induced neural plasticity. PMID- 7981872 TI - Eye saccade dynamics during paradoxical sleep in the cat. AB - Cat eye movements were recorded during wakefulness and paradoxical sleep with the technique of the scleral search coil in a magnetic field. During waking, eye movements consisted of a succession of saccades and fixation phases. During paradoxical sleep, the pattern of eye movements displayed drifts of variable velocity and direction and short fixation phases, upon which saccades superimposed. These saccades displayed a repetitive, stereotyped, asymmetrical pattern. The maximum velocity/amplitude relationships, i.e. the main sequences, were determined for spontaneous and visually induced saccades of waking and for the following types of saccades during paradoxical sleep: (i) isolated saccades accompanied by ponto-geniculo-occipital (PGO) waves, (ii) isolated saccades accompanied by eye movement potentials (EMP), and (iii) saccades in bursts accompanied by PGO waves. The slope of the main sequence relationship of any type of paradoxical sleep saccade (from 21.7 degrees/s/degree for isolated saccades to 35.6 degrees/s/degree for saccades in bursts) was higher than that of any type of waking saccade (11.2 degrees/s/degree for spontaneous saccades to 14.7 degrees/s/degree for visually elicited ones). Furthermore, during paradoxical sleep, saccades in bursts were faster than isolated ones. This demonstrates that different neurophysiological mechanisms subserve the generation of waking saccades, paradoxical sleep isolated saccades and paradoxical sleep saccades in bursts, or that the oculomotor system is in a different state of excitation during these different sets of saccades. These findings throw new light on the functioning of the oculomotor system during paradoxical sleep and are discussed in terms of the functional significance of paradoxical sleep saccades and PGO waves. PMID- 7981873 TI - Host serotonin axons innervate intrastriatal ventral mesencephalic grafts after implantation in newborn rats. AB - This study investigated the potential of immature and adult serotonin (5-HT) neurons for axonal growth into intrastriatal grafts of ventral mesencephalic tissue. Implantation of dissociated fetal (embryonic days 14-15) ventral mesencephalic tissue was carried out in immature [postnatal days (P) 5-14] and adult rat neostriatum. The brains were processed 2-6 months later for dopamine and 5-HT immunocytochemistry. A few grafts implanted into adult and P7 recipients contained small numbers of cotransplanted 5-HT cell bodies. These also displayed a rich network of 5-HT axons, even in adult rats prelesioned with 5,7 dihydroxytryptamine, indicating the graft origin of these axons. All other grafts were totally devoid of 5-HT cell bodies. After implantation in adults, such grafts contained rare 5-HT axons. In contrast, in P5-P7 recipients, they displayed many 5-HT fibres, which were uniformly distributed. Such was no longer the case after implantation in P14 recipients, which showed minimal 5-HT innervation, as in adult recipients. Processing of naive rat brain at different ages for 5-HT immunocytochemistry showed that 5-HT axons were still clearly less numerous in the neostriatum at P21 than in adults, whereas in the substantia nigra the 5-HT innervation developed more rapidly and was comparable, at P21, to that of adults. It was concluded that 5-HT axons are able to grow into ventral mesencephalic grafts, but mainly at the fetal stage and with decreasing capacity after birth.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7981874 TI - Expression of the cyclic AMP-dependent protein kinase (PKA) catalytic subunit from a herpes simplex virus vector extends the survival of rat sympathetic neurons in the absence of NGF. AB - Superior cervical ganglion neurons from neonatal rats are dependent on nerve growth factor for their survival both in vivo and in vitro. In culture this requirement can be largely replaced by cAMP or its analogues. Since activation of protein kinase A by cAMP is likely to be the pathway by which it exerts its survival-promoting effect, we have tested the feasibility of using herpes simplex virus (HSV) as a vector for expressing survival-promoting genes in neurons by cloning the catalytic subunit of the cAMP-dependent protein kinase (PKAcat) with a metallothionein gene promoter into the HSV thymidine kinase gene by homologous recombination. About 95% of the neurons became infected using 2.5 p.f.u. per cell. When this construct was used to express PKAcat in superior cervical ganglion neurons, in the presence of nerve growth factor (NGF) increases of 1.9- to 2.4-fold in PKA activity were found 8-10 h after infection; levels remained elevated (1.4- to 2.1-fold) up to 18 h, returning to basal by 24 h. After infection in the absence of NGF, cumulative activity over 24 h was approximately 3.5-fold lower in the first 24 h. Although the level of the inhibitory regulatory subunit type I was raised by 18 h, this is unlikely to completely explain the transient activity of PKAcat. When neurons were induced to express maximum PKAcat levels in the presence of NGF and then deprived of NGF, survival was extended by up to 2 days, demonstrating a direct role for PKA in promoting survival. By this time, some neurite degeneration was beginning which appeared to be partly due to toxic effects of the virus. However, replenishment with NGF supported further survival, showing that at this time the neurons were still viable. Similar rates of survival were obtained using a tsK-based PKAcat vector, but no significant survival was obtained with parental HSV or tsK virus strains. These data demonstrate the feasibility, and highlight some of the problems, of using HSV based vectors as tools for expressing functional survival proteins in sympathetic neurons. PMID- 7981875 TI - Opposing excitatory and inhibitory influences from the cerebellum and basal ganglia converge on the superior colliculus: an electrophysiological investigation in the rat. AB - We recently showed (Westby et al., Eur. J. Neurosci., 5, 1378-1388, 1993) that the cerebellar interpositus nucleus is a source of excitatory drive for a population of spontaneously active neurons in the lateral intermediate layers of the contralateral superior colliculus. Anatomical and physiological studies have shown that this region of the colliculus contains cells of origin of the crossed descending tectoreticulospinal tract and receives GABAergic input from the ipsilateral basal ganglia. In the present study we tested the hypothesis that the same neurons receiving excitatory drive from the cerebellum also receive tonic inhibitory input from the substantia nigra pars reticulata. From a sample of 73 spontaneously active collicular cells we found that in 53% the firing rate was suppressed by GABA microinjection into the contralateral deep cerebellar nuclei; a further 15% showed a frequency increase. Of the collicular cells identified as receiving excitatory cerebellar input, 85% were found to be disinhibited by nigral GABA microinjection. The remainder were all inhibited by nigral GABA. These data show that the main excitatory influence from the cerebellum and the main inhibitory influence from the substantia nigra converge on at least one population of spontaneously active cells in the lateral intermediate layers of the superior colliculus. This finding is discussed in relation to the possible function of these spontaneous cells in movement control and nociception. PMID- 7981876 TI - Regulation of neuropeptides in adult rat forebrain by the neurotrophins BDNF and NGF. AB - The expression of neuropeptides and neurotrophic factors is altered in the hippocampus after seizure induction in rats. Because the increase in brain derived neurotrophic factor (BDNF) and nerve growth factor (NGF) mRNAs precede changes in neuropeptide expression after seizure, it is possible that BDNF and NGF mediate subsequent alterations in peptide expression. To test this hypothesis directly, BDNF or NGF was infused into the hippocampus and cortex of adult rats. To ascertain the regional specificity of any observed effects of neurotrophin administration on neuropeptide expression, infusions into the striatum were also studied. To control for specificity, vehicle was also infused into the same sites. Peptide and mRNA alterations were assessed by Northern analysis, immunohistochemistry and radioimmunoassay. BDNF produced elevations of peptide and mRNA for neuropeptide Y and cholecystokinin in hippocampus and cortex, and somatostatin in cortex. BDNF increased mRNAs for neuropeptide Y, cholecystokinin, substance P and dynorphin in striatum. In contrast, BDNF decreased dynorphin peptide and mRNA in hippocampus. NGF's effects were limited to small mRNA increases, without corresponding changes in peptide levels, for neuropeptide Y in hippocampus and striatum, substance P in cortex and cholecystokinin in striatum. The distinct and limited effects of NGF infusion on neuropeptide expression demonstrate that BDNF's effects are not non-specific results of protein infusion into the brain. These findings indicate that BDNF may play a regionally specific role in modulating neuropeptide expression in the normal brain as well as in various pathophysiological states. PMID- 7981877 TI - Low density, but not high density, C6 glioma cells support dorsal root ganglion and sympathetic ganglion neurite growth. AB - Accumulating evidence suggests that an inhibitory influence of the environment on growth cones plays a crucial role in development and regeneration of neuronal projections. Oligodendrocyte-associated neurite growth inhibiting substance is one of the most extensively studied molecules. Molecular biological studies, however, remain slow in progress. Although finding clonal cells that express such factors would facilitate the analysis of inhibitory influences on neurite growth, few cell lines have been reported to express neurite growth inhibitor. We therefore investigated the possibility of a clonal glial cell line to differentiate and express inhibitory or non-permissive features for neurite outgrowth in culture. We chose the C6 glioblastoma cell line and examined neurite extension from chick dorsal root ganglion (DRG) explants. Neurites from embryonic day 9 DRG extensively grew on C6 cells that were cultured at low cell density, while they failed to grow on C6 cells cultured at high density, even in the presence of nerve growth factor in high concentrations. Membrane extract from high density C6 cells, when used as culture substratum, was less permissive for neurite outgrowth compared to extract from low density cells. Treatment of the membrane extract derived from high density C6 cells with trypsin made it less non permissive for neurite growth. These results suggest that C6 cells are induced to express a non-permissive property for neurite outgrowth by culturing them at high density. PMID- 7981879 TI - Opposing roles for dopamine D2 and D3 receptors on neurotensin mRNA expression in nucleus accumbens. AB - Using in situ hybridization histochemistry in rat nucleus accumbens, we show that the dopamine D3 receptor mRNA is expressed in the ventromedial part of the shell subdivision, where its gross distribution matches that of neurotensin mRNA. In addition, hybridization studies at the cellular level show that a large fraction of the neurotensin neurons co-express the D3 receptor mRNA in this restricted area. In contrast, the dopamine D2 receptor mRNA is expressed mainly in the core and marginally in the shell, at the level of the cone. In rats treated by haloperidol and sulpiride, two D2-like receptor antagonists, but not by SCH 23390, a D1-like receptor antagonist, proneurotensin mRNA was increased in the D2 receptor mRNA-rich areas but decreased in the D3 receptor mRNA-rich areas. This suggests that the D2 and D3 receptors control neurotensin mRNA expression negatively and positively, respectively. PMID- 7981878 TI - Prefrontal corticostriatal afferents maintain increased enkephalin gene expression in the dopamine-denervated rat striatum. AB - The cortical contribution to the maintenance of preproenkephalin (PPE) and preprotachykinin (PPT) mRNA levels in the rat striatum was investigated using quantitative in situ hybridization histochemistry. The effects of knife-cut transections of the frontal cortical pole on the expression of PPE and PPT mRNA in rat striatal neurons was studied in intact striata and in striata previously denervated by a 6-hydroxydopamine (6-OHDA) lesion of the mesencephalic dopamine pathways. Lesions of the dopaminergic striatal afferents resulted in marked increases in the mRNA encoding PPE throughout the striatum, including the ventral striatum and nucleus accumbens, while the levels of PPT mRNA were considerably reduced in these structures. Knife-cut lesions of the frontal cortical pole, transecting the prefrontal corticostriatal projection at the level of the foreceps minor, displayed little or no effect on the expression of either PPE or PPT mRNA in the dopamine-intact striatum. Conversely, frontal cortical transections performed 4 weeks after the 6-OHDA lesions reversed the 6-OHDA lesion-induced increase in PPE mRNA in the striatum as well as in the ventral striatum and nucleus accumbens. The down-regulation of PPE mRNA in the dopaminergically denervated striatum was most pronounced in the medial part, which is the area most densely innervated by the frontal cortical pole. Here, the level of PPE mRNA expression per striatal cell was similar to the intact striatum. In contrast, the cellular expression of PPE mRNA remained up-regulated in the lateral striatum, which receives more sparse innervation from the frontal cortical pole. Cortical transections did not significantly affect the 6-OHDA lesion-induced down-regulation of PPT mRNA in any of the striatal regions analysed. The present results demonstrate that knife-cut transections of the frontal corticostriatal pathway are capable of reversing the increased striatal PPE mRNA levels, but not the decreased PPT mRNA levels, induced by a 6-OHDA lesion of the dopaminergic input. These observations suggest that in the absence of a functional striatal dopamine input, augmented glutamatergic transmission in corticostriatal afferents is necessary to maintain increased levels of PPE mRNA expression, and hence also enkephalin synthesis, in striatal projection neurons. PMID- 7981880 TI - Simplified sulfidoleukotriene ELISA using LTD4-conjugated phosphatase for the study of allergen-induced leukotriene generation by isolated mononuclear cells and diluted whole blood. AB - By using leukotriene D4 (LTD4)-labeled alkaline phosphatase (LTD4-AP) and a mouse monoclonal anti-sulfidoleukotriene (sLT) antibody (1A-LDR1), we developed a solid phase competition ELISA for sLTs. The detection limit of this assay was 6.3 +/- 1.2 pg sLT/100 microliters (mean +/- SEM; n = 10). Intraassay variations at 15, 50 and 150 pg sLT/well (9.8, 13.5 and 12.3%, respectively), the corresponding interassay variations (32.1, 11.9 and 18.8%, respectively) and the good correlation with a commercial radioimmunoassay (r = 0.97; n = 43) confirmed the validity of this ELISA. Furthermore, the assay had a low background and gave a 70 90% recovery of LTD4 added to medium containing up to 10% serum. In contrast to another sLT ELISA using the same antibody but based on competition with solid phase LTE4-BSA, our assay is about 7-fold more sensitive. It also requires about 40 times less leukotriene for conjugate production than the previous method for the same number of determinations. The assay allows measurement of sLTs generated by small numbers of basophils present in isolated mononuclear cells or diluted whole blood in response to allergen, and allows simple and rapid determination of basophil reactivity to suspected allergens. PMID- 7981881 TI - Interleukin-2 and interferon-gamma production by peripheral blood lymphocytes of patients with common variable immunodeficiency. AB - We evaluated the production of interleukin-2 (IL-2) and interferon-gamma (IFN gamma) in peripheral blood lymphocytes (PBLs) from six patients with common variable immunodeficiency (CVID). IL-2 production and IFN-gamma concentrations were not reduced in these patients. As the production of IL-2 and IFN-gamma secreted from TH1 clones was within the normal range in patients with CVID, we concluded that TH1 function was normal in these patients. Our previous report showed B-cell dysfunction in CVID patients. Therefore, we concluded that the immune defect in these patients is caused by B-cell dysfunction rather than T cell dysfunction. PMID- 7981882 TI - Ten-year follow-up in pediatric patients with allergic bronchial asthma: evaluation of specific immunotherapy. AB - Specific immunotherapy as a treatment for bronchial asthma has been a controversial field. A collaborative study was designed in an attempt to further define the possible contribution of specific immunotherapy in a pediatric population. One hundred and sixty-six patients were treated with immunotherapy and 248 received no immunotherapy. The results were compared during 10 years of follow-up in both groups. There was a significant decrease in the number of acute crisis in the treated group (p < 0.05). However, no differences were seen in the number of hospital admissions or in the quality of life between the treated and untreated groups. The treated group required significantly fewer drugs (p < 0.05). Thus, it is probable that the untreated group shows the same clinical indexes as the treated group due to their increased use of medication. Specific immunotherapy represents an effective treatment that changes the natural course of allergic bronchial asthma in pediatric patients. PMID- 7981883 TI - In vivo evaluation of cellular immunity in different phases of contact dermatitis. AB - Contact dermatitis is a delayed hypersensitivity reaction involving the skin as shock organ. In a delayed cutaneous hypersensitivity reaction to contact with an antigen, the afferent, central and efferent phases of the immune reaction remain untouched and the individual concerned has a nonspecific inflammatory response capacity. Hence, delayed cutaneous hypersensitivity tests and the dinitrochlorobenzene (DNCB) test are of great use in evaluating this type of reaction. This prompted us to evaluate the in vivo response of patients suffering from contact dermatitis, as studies on this topic have been focused on animal experimentation or in vitro techniques. We chose 30 patients with contact dermatitis and studied them at three different stages, namely, when the patients showed the typical clinical signs (acute phase), when the lesions had subsided (intercrisis phase) and when the signs had recurred (acute outbreak). We subjected them to delayed cutaneous hypersensitivity tests and the DNCB test. Both techniques revealed a decrease in the response in the intercrisis phase with respect to the other two phases and to a control group. PMID- 7981884 TI - Effects of boldine on cellular immune functions in vitro. AB - The in vitro effects of boldine on natural killer (NK) cells, lectin-dependent cell-mediated cytotoxicity (LDCC) and lectin-induced blast transformation were studied in patients with breast cancer, chronic lymphocytic leukemia (CLL) and healthy donors. NK activity was measured against [51Cr]-labeled K-562 targets cells. LDCC and natural cell-mediated cytotoxicity (NCMC) were assessed using [3H]-thymidine-prelabeled HEp-2 cells. Lectin (PHA and Con A)-induced blast transformation was measured by thymidine incorporation. Boldine concentration dependently decreased blastogenesis in normal subjects and patients with CLL. However, the decrease in breast cancer patients was significant only at higher concentrations. NK activity showed no change in healthy controls with normal values, but in cases with low activity treatment with boldine resulted in an increase. In patients with CLL, NK activity was enhanced; in tumor-bearing patients, however, there was no effect. LDCC and NCMC activity did not change significantly in normal controls. In patients with CLL, NCMC activity significantly increased. In tumor-bearing patients, LDCC activity was strongly enhanced by higher concentrations of boldine, whereas NCMC activity changed significantly only at the concentration of 1.0 microgram/ml. PMID- 7981885 TI - A citrus fruit-exclusion diet in sensitive patients and its influence on specific antibodies. AB - The presence and kinetics of specific IgE and IgG antibodies against the oranges Citrus aurantium sinensis (CAS) and Citrus silension (CS) were studied in 41 atopic and 20 non-atopic children aged 8-12 years. Diagnostic procedures such as intracutaneous skin tests, IgE PRIST and anti-CAS and anti-CS IgE and IgG RAST were performed in both groups. A citrus fruit-exclusion diet was maintained for 180 days. The comparison of the results before and after the diet showed no significant changes in skin reactivity and RAST values, and even a slight increase was recorded in the latter. We have attempted to explain these puzzling findings. PMID- 7981886 TI - The role of platelet-activating factor (PAF) in interstitial pulmonary disease. AB - Platelet-activating factor (PAF) is a biolipid of crucial importance in the inflammatory response. In the first part of this work we review the basic biochemical characteristics of PAF. Also, the production and degradation of PAF by inflammatory cells is detailed in depth, with a description of enzymes linked to these processes. Subsequently, we examine the main characteristics of the generation of PAF by pulmonary cells, with emphasis on its production by alveolar macrophages. We then discuss in depth the effects of this biolipid on the inflammatory cells present in interstitial disease. In this part of the review we describe the direct effect of PAF on polymorphonuclear leukocytes (neutrophils and eosinophils), mononuclear phagocyte system cells, lymphocytes and endothelial cells. We then examine the indirect effect of PAF on inflammatory cells (mainly due to an interaction with neuropeptides). Finally, we discuss the data on the role of PAF in diffuse interstitial pulmonary disease (both human and experimental). PMID- 7981887 TI - Systemic anaphylaxis due to hepatic hydatid disease. AB - Hydatidosis can be a cause of anaphylaxis; it has been clearly established that the accidental rupture of a cyst during surgery can provoke severe anaphylactic reactions. Spontaneous anaphylaxis secondary to hydatid disease is much less frequent. We report three patients who presented with spontaneous anaphylaxis without apparent cause. Serological and ultrasonographic studies showed hepatic hydatid disease. Two years after surgical resection of cysts, no new episodes of anaphylaxis have occurred. Hydatidosis is a cause of apparently spontaneous anaphylaxis and this is likely due to an IgE-mediated mechanism. PMID- 7981888 TI - The coming era of cancer genetic screening. PMID- 7981889 TI - Effects of fixative and fixation time on the extraction and polymerase chain reaction amplification of RNA from paraffin-embedded tissue. Comparison of two housekeeping gene mRNA controls. AB - A number of reports have indicated that RNA recovered from paraffin-embedded tissue can be used as a substrate in the polymerase chain reaction (PCR). Although it is established that RNA in paraffin-embedded tissue undergoes significant degradation, the specific contributions of different fixatives and fixation times to this degradation are not known. Mouse splenic tissue was harvested and fixed immediately for 2, 8, or 24 h in either formalin, Omnifix II, or Carnoy's fixative and then processed and embedded in paraffin. RNA was extracted from deparaffinized cubes of tissue using an adaptation of the technique described by Chomczynski and Sacchi. RNA was reverse transcribed using a random hexamer primed reaction. PCR amplification for cDNAs of the housekeeping genes glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and hypoxanthine phosphoribosyltransferase (HPRT) mRNAs was then performed. Although GAPDH amplification is used routinely on fresh and frozen tissues, we show that the presence of DNA contamination in the RNA preparations limits its usefulness in paraffin-embedded tissue. Amplifiable HPRT mRNA sequences were detected in nine of 12 samples fixed in Omnifix II, in four of 12 samples fixed in Carnoy's fixative, and in none of 12 formalin-fixed samples. Because of primer selection to preclude amplification of genomic HPRT, DNA contamination is not an issue when HPRT is amplified. Thus, HPRT represents the control system of choice for the evaluation of RNA in PET. The techniques described provide a rapid, uniform, and reproducible method of obtaining RNA from PET for molecular analysis, but they indicate limited utility for retrospective analysis of archival tissues. PMID- 7981890 TI - Influence of formalin fixation on the detection of cytomegalovirus by polymerase chain reaction in immunocompromised patients and correlation to in situ hybridization, immunohistochemistry, and serological data. AB - The possibility of detecting cytomegalovirus (CMV) in formalin-fixed tissues by polymerase chain reaction (PCR) was evaluated in necroposies from lung tissues in a total of 24 patients who either had received organ transplants or were immunocompromised. PCR using two different pairs of primers for amplification of the major immediate early antigen of CMV was performed on fresh tissues and tissues fixed for 24, 48, and 72 h in neutral buffered formalin and compared to immunohistochemistry (IHC) and in situ hybridization (ISH). The fresh tissues of nine patients with serological evidence for acute CMV infection were all positive for CMV by PCR. After formalin fixation, the majority of the patients failed to show distinct signals with one or both pairs of primers as measured by densitometry. In contrast to this, fresh tissues of 15 patients without signs of an acute CMV infection were found either negative or weakly positive by PCR. Using IHC or ISH, positive results were observed only in five of nine and four of nine patients with acute CMV infection, respectively. These data demonstrate that, if only formalin-fixed tissue is available, PCR for CMV detection should be performed using two pairs of primers and should be supported by IHC. PMID- 7981892 TI - In situ hybridization analysis of lymphoproliferative disorders. Assessment of clonality by immunoglobulin light-chain messenger RNA expression. AB - Determination of clonality in B-cell lymphomas is a useful diagnostic adjunct. In situ hybridization (ISH) for the detection of kappa and lambda mRNAs has the potential to overcome some common specimen-related limitations in clonal assessment. Tritium-labeled antisense cRNA probes directed at conserved segments of the constant regions of the kappa and lambda mRNAs were used in an autoradiographic method to detect B-cell clonality. Using these probes, we analyzed 103 formalin-fixed, paraffin-embedded biopsy samples, and the results were subsequently compared to available immunophenotypic (all cases) and genotypic (50 cases) data. Of 103 samples, 82 (80%) had adequate RNA preservation as determined by actin RNA signals, and 73 (89%) of the 82 cases demonstrated concordant clonality assignment by both ISH and immunophenotyping. The remaining nine cases showed a specific form of discordance in that each exhibited no protein (Ig) expression but had evidence of mRNA immunoglobulin light-chain expression. Forty-five (90%) of 50 cases evaluated for immunoglobulin and T-cell receptor beta-gene rearrangements demonstrated concordant results with respect to clonality assignment by ISH. Thus, ISH demonstrates adequate sensitivity with respect to traditional methods of clonality assessment. However, its practical utility awaits the development of nonradioactive detection methods with adequate sensitivity to improve turnaround time. PMID- 7981891 TI - Gelatinase A (MMP-2) and its mRNA detected in both neoplastic and stromal cells of tumors with different invasive and metastatic properties. AB - Simultaneous presence of gelatinase A (MMP-2) and MMP-2 messenger RNA (mRNA) in 30 malignant tumors with various degrees of differentiation and biological behavior was evaluated by immunohistochemistry and in situ hybridization. The series consisted of 10 gastric carcinomas, 10 colorectal carcinomas, five squamous skin carcinomas, and five basal cell skin tumors. MMP-2 was detected in all cases. MMP-2 mRNA was expressed in the stromal cells in all cases and was more marked in the less-differentiated gastric and colonic carcinomas; it was also detected in the neoplastic cells of poorly differentiated tumors, particularly in those of the signet-ring cell type, both in the colon and stomach. The study confirmed that stromal cells have a specific role in tumor invasion and suggests a direct relationship between neoplastic epithelium and stromal cells in the most aggressive varieties. PMID- 7981893 TI - The presence of bcl-1 and bcl-2 gene rearrangements in diffuse small cleaved-cell lymphoma. A disease with diverse molecular and immunophenotypic findings. AB - Clonal rearrangements of the bcl-1 and bcl-2 protooncogenes are found in many B lineage non-Hodgkin's lymphomas (NHL) and may play a role in their pathogenesis. We investigated rearrangements of the bcl-1 and bcl-2 protooncogenes in 13 cases of B lineage diffuse small cleaved-cell lymphoma (DSCL), and correlated the results with clinical history, immunophenotype, and outcome. Six cases showed bcl 2 rearrangements, including four patients with an antecedent follicular small cleaved-cell lymphoma (FSCL). Two patients had a bcl-1 rearrangement, including one with a previous FSCL. Of the five patients who lacked detectable bcl-1 or bcl 2 rearrangements, one had an FSCL history. Similar to the lack of correlation between clinical history and genotype, there was no correlation between genotype and immunophenotype. Our results indicate that although DSCL is a morphologically uniform disease, different molecular genetic pathways are involved in its genesis. Follow-up showed four of the six DSCL patients with bcl-2 rearrangements were alive with a median survival of 56 months, whereas the median survival of the seven patients lacking a bcl-2 rearrangement was 17 months and included only one survivor. Thus bcl-2 rearrangements in DSCL may define a patient subset with a more indolent genetic abnormality and prolonged survival. PMID- 7981894 TI - Expression of Kirsten-ras p21 in gastric cancer correlates with tumor progression and is prognostic. AB - The purpose of this study was to determine the correlation between expression of ras oncoproteins and the tumor stage or outcome of patients with gastric carcinoma. After the specificity of each anti-ras monoclonal antibody was confirmed by protein immunoblot analysis, immunohistochemical assays for a common ras antigen present in N-, Harvey- and Kirsten (K)-ras oncoproteins, as well as for K-ras specific antigen, were performed on paraffin-embedded carcinoma tissue from 110 patients who underwent curative resection. By Western blot analysis, there was more p21 in fresh cancer specimens than in normal specimens. K-ras expression distinguished advanced from early gastric carcinoma and correlated with depth of cancer invasion. Among the 110 patients, survival rates of those with carcinomas positive for the common-ras or K-ras antigens were significantly lower than of those with antigen-negative carcinomas (p < 0.05). In a multivariate analysis, nodal involvement (p = 0.002), serosal invasion (p = 0.012) and K-ras p21 expression (p = 0.044) were independently predictive of the recurrence. These results suggest that K-ras p21 is a useful marker of tumor progression and poor prognosis after curative resection. PMID- 7981895 TI - Evaluation of Biohit HPV Screening and Typing kits in detection of human papillomavirus DNA from lesions of anogenital tract. AB - The Biohit HPV Screening and Typing kits for in situ hybridization of human papillomavirus (HPV) DNA are now commercially available. The HPV Screening kit contains a cocktail of HPV probes, and the Typing kit contains separated hybridization probes for HPV 6, 11, 16, 18, 31, and 33. They were evaluated by comparison with an in situ hybridization (ISH) method, using the Pathogene HPV probes 6/11, 16/18, 31/33/51. One hundred anogenital biopsies from 78 women and 22 men were tested. Among them, 43% showed normal or inflammatory mucosa, 44%, koilocytosis or mild dysplasia, and 13%, moderate to severe dysplasia. Altogether, 60 specimens were positive with the ISH reference method: 17 with the HPV 6/11 probe, 12 with the HPV 16/18 probe, 16 with the HPV 31/33/51 probe, and 15 had mixed infections. The agreement between the Screening test and the homemade ISH is 91%. The Screening test has a sensitivity of 93% and a specificity of 87%. As for the Biohit Typing test, four false-negative samples, and partial or total discordance in nine and four samples, respectively, were observed when compared to our reference method. Thus the agreement between both typing ISH tests is 92%. The sensitivity of the Biohit Typing test is 93%, and the specificity, 91%. The sensitivity decreases to 72% when the 31 and 33 probes are evaluated separately. The Biohit Screening assay is simple, reliable, reproducible, and suitable for rapid routine screening. The Biohit Typing test allows the detection of a specific type of HPV DNA and also permits, in mixed HPV infection, definition of the type of associated HPV DNA.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7981896 TI - PCR production of a digoxigenin-labeled probe for the detection of human cytomegalovirus in tissue sections. AB - In situ hybridization (ISH) provides a means for identifying viral genomes in the context of tissue pathology. We have developed a specific and sensitive ISH probe for the detection of cytomegalovirus (CMV) DNA in formalin-fixed, paraffin embedded tissue sections. Digoxigenin-11-dUTP was incorporated into a 435-base pair fragment of the CMV Major Immediate Early (MIE) gene with use of the polymerase chain reaction (PCR). Hybridized probe was detected by reaction with antidigoxigenin antibody coupled to alkaline phosphatase and chromogenic substrates. This method has detected CMV infection in routine clinical specimens from a variety of tissue types, including colon, kidney, liver, and stomach. Infection in cells with and without characteristic inclusions is revealed with this probe. The background is so low that single infected cells are detected unambiguously. No cross-hybridization was observed with cells infected with other viruses of Herpesviridae. This approach may be useful for producing probes for the detection of other viral genomes in tissue sections. PMID- 7981897 TI - Widespread aluminium deposition in extracerebral organ systems of patients with dialysis-associated encephalopathy. AB - We have described new silver-staining methods for the demonstration of lesions in senile dementia of the Alzheimer type. The same procedure was used to visualize characteristic aluminium (Al)-containing inclusions in choroid epithelium, glia and neurons of the central nervous system in dialysis-associated encephalopathy (DAE). Here we describe the patterns and degree of Al deposition in extracerebral tissues of 12 DAE autopsy cases. Light microscopy of silver-stained paraffin sections demonstrated autonomic ganglion cells filled with numerous intracytoplasmic black-stained fine granular inclusions, which were also seen in endocrine tissues (pituitary, parathyroid and adrenal) and in Leydig cells. Heart, liver cells and the testicular tubules were involved, but decalcified bones, haematopoetic elements, hyperplastic epithelium and one case of malignant epithelium lacked inclusions. Laser microprobe mass analysis revealed prominent Al-related mass signals within the en-bloc silver-stained inclusions which were seen at low intensity in adjacent non-stained structures. Electron microscopy demonstrated accumulations of small electron-dense granules intermingling with lipopigments. PMID- 7981898 TI - A new type of a lethal osteochondrodysplasia with angel-shaped brachyphalangy. AB - A hydropic stillborn female fetus of 22 weeks gestation with shortlimbed skeletal dysplasia and brachyphalangy is described. The markedly shortened phalanges of both hands had a most unusual angel-like configuration radiologically. Histological examination and comparison with a normal hand of the same gestational age revealed this appearance to be due to disturbed enchondral ossification with premature calcification of epiphyseal cartilage and thickening and outfolding of diaphyseal bone as wing-shaped appositions. Magnetic resonance imaging of the fetus demonstrated marked hyperplasia of cartilage, most impressive in the pelvis. This new type of lethal bone dysplasia may be placed in the group of metatropic dysplasias and similar disorders. PMID- 7981899 TI - Stromal tumours of the gastrointestinal tract: a clinicopathological and ploidy analysis of 33 cases. AB - The clinicopathological and DNA flow cytometric data of 33 patients with stromal tumours of the gastrointestinal tract (STGIT) were analysed to select pathological features of prognostic value. Tumours had been previously classified as benign (21 cases) or malignant (12 cases). Data relating to poor prognosis statistically were local invasion, pathological grade, size greater than 10 cm, mitotic index (MI) and necrosis. Pathological grade was related to local invasion. Aneuploidy did not correlate with poor survival although a common trend was detected between both. DNA content may help to predict prognosis of STGIT, but its real value has not yet been clearly established. Currently, stage (invasion), size, MI and pathological grade remain the most useful prognostic factors. PMID- 7981900 TI - An interleukin-1 receptor antagonist decreases fibrosis induced by dimethylnitrosamine in rat liver. AB - The main pathological feature of liver fibrosis is the accumulation of extracellular matrix associated with hyperplasia and activation of perisinusoidal (Ito) cells (PSC) to myofibroblast-like cells. Interleukin-1 enhances collagen synthesis by increasing the proliferative activity of cultured PSC and has been implicated in the pathogenesis of hepatic fibrosis. Interleukin-1 receptor antagonist (IL-1ra) can block the binding of IL-1 to its receptors and act as a natural inhibitor of IL-1. We have examined whether the administration of IL-1ra can interfere with the development of experimental cirrhosis induced by dimethylnitrosamine (DMN). Rats were divided in three groups and received respectively DMN, DMN + IL-1ra and IL-1ra. For each group the collagen content of the hepatic tissue and the volume density of the inflammatory infiltrate were measured. Immunostaining for laminin and alpha-smooth muscle actin were also performed. In animals given DMN + IL-1ra we observed a decreased deposition of laminin and collagen, and a decreased number of laminin-positive PSC and of alpha smooth muscle actin reactive cells, compared with animals receiving DMN alone. The present findings suggest that the early activation of PSC in vivo is at least in part mediated by IL-1 and confirm that the administration of IL-1ra may be of interest in modifying the biological effects of IL-1. PMID- 7981901 TI - Immunohistochemical distributions of cathepsin B and basement membrane antigens in human lung adenocarcinoma: association with invasion and metastasis. AB - The distributions of cathepsin B (CB) a lysosomal cysteine proteinase, type IV collagen (CIV) and laminin (LM), which are main components of basement membranes (BMs) were studied in a series of 64 human lung adenocarcinomas using an immunohistochemical technique. Over-expression of CB (> 80% positive cells) was significantly associated with the grade of tumour differentiation (p < 0.01), with lymph node metastasis (p < 0.01) and with BM degradation (p < 0.01) detected by the staining pattern of CIV and LM. It was significantly associated with a prognostic disadvantage (p < 0.01). The immunohistochemical staining pattern of CB has a close relationship with degradation of BM, and may be used as a marker for tumour metastasis and prognosis in lung adenocarcinoma. PMID- 7981903 TI - The prevalence of BCL-2 immunoreactivity in breast carcinomas and its clinicopathological correlates, with particular reference to oestrogen receptor status. AB - BCL-2 protein plays a pivotal role in overriding programmed cell death (apoptosis), thus favouring a prolonged survival of normal and neoplastic cells. Expression of the bcl-2 gene has been documented in some human tumours (non Hodgkin's lymphomas and prostatic adenocarcinomas), but findings in breast carcinomas have not been reported. We have used the monoclonal antibody 124 to investigate BCL-2 expression in 212 breast carcinomas, and to correlate it with the oestrogen (ER), progesterone (PR) and epidermal growth factor receptor (EGFR) status, and with other clinicopathological variables including tumour type, grade, stage, growth fraction (as evaluated by Ki-67 immunostaining), and p53 accumulation. Of the 212 carcinomas, 173 (81.6%) exhibited BCL-2 immunoreactivity in more than 25% of the neoplastic cells. BCL-2 immunoreactivity was strongly correlated with ER and PR expression (P < 0.00001), with the lobular type (P = 0.012) and with better differentiated neoplasms (P = 0.00003), whereas it was inversely correlated with EGFR (P < 0.00001), p53 (P = 0.0004) and Ki-67 (P = 0.0002) immunoreactivities. No association was found with tumour stage (T and N categories). We conclude that bcl-2 expression in breast cancers is related to the oestrogen-dependent transcription pathway. PMID- 7981902 TI - Proliferating cell nuclear antigen in breast carcinomas. An immunohistochemical study with correlation to histopathological features and prognostic factors. AB - Proliferating cell nuclear antigen (PCNA), was examined by immunohistochemistry in 509 breast carcinomas. The immunoreactivity was found to be independent of the length of fixation when the tissue sections were microwaved before incubation with the primary antibody. The PCNA immunoreactivity was assessed by two semi quantitative methods, which were correlated but not exchangeable. The comedo type of intraductal carcinomas and invasive ductal carcinomas had a higher PCNA score than other types. Lymph node metastases had a significantly higher PCNA score than primary carcinomas. High PCNA immunoreactivity was correlated with the presence of lymph node metastases, absence of tubule formation, numerous mitoses, severe nuclear pleomorphism, high histological grade and absence of progesterone receptors (PgR). PCNA in lymph node positive tumours was correlated with tumour type, especially with ductal carcinomas, absence of tubule formation, high histological grade and absence of PgR, whereas PCNA in lymph node negative tumours was correlated with large tumour size, numerous mitoses, severe nuclear pleomorphism and high histological grade. Number of mitoses and nuclear pleomorphism were the two most important factors in predicting the PCNA score; the absence of PgR and nuclear pleomorphism were important in lymph node negative and positive tumours, respectively. In a univariate analysis high PCNA score was found to be correlated with shorter relapse-free period and poorer over-all survival. PMID- 7981904 TI - Primary retroperitoneal mucinous cystoadenocarcinomas: an immunohistochemical and molecular study. AB - Special immunohistochemical stains for the identification of gastroenteropancreatic antigens in two cases of primary retroperitoneal mucinous cystoadenocarcinomas (PRMC) show that these tumours have patterns similar to ovarian mucinous tumours. Markers of pyloric type gastric mucosa differentiation (M1, cathepsin E, concavavalin A, pepsinogen II) are mostly positive in benign and borderline areas with endocervical type differentiation, while immunoreactivity for intestinal cell markers (M3SI and CAR-5) and for DU-PAN-2 is present mainly in frankly malignant areas, regardless of differentiation type. DNA analysis shows a point mutation of K-ras oncogene at codon 12 (GGT to CGT) in one case. The immunohistochemical and genotypic similarity of PRMC and ovarian mucinous tumours may indicate similar mechanisms in their histogenesis. PMID- 7981905 TI - Isolation, growth and characteristics of human ovarian surface epithelium. AB - The ovarian surface epithelium (OSE) is a key tissue in the pathogenesis of ovarian surface epithelial-stromal tumours and ovarian endometriosis, commonly encountered gynaecological diseases. Despite the high incidence of these diseases, experimental in vitro studies of OSE are few and so we used the scraping method with an enzymatic procedure to isolate human OSE and studied its characteristics in vitro. Nineteen normal ovaries were used. After incubation of the ovary for 40 min in collagenase type 1 solution (300 U/ml), the surface cells were removed by gentle scraping with a surgical blade. Cells obtained as a cluster after unit gravity sedimentation with 5% bovine serum albumin in medium 199 were cultured in medium 199 containing 15% fetal bovine serum. The viable cell number in a single ovary was 0.1-2.7 x 10(6). The outgrowth of cells started from a homogeneous population of single cells, and the cell population doubling time was between 7 and 10 days. Confluent monolayers were formed after 13-20 days and subcultured from one to three times. The monolayers mostly had a cobblestone appearance, and fusiform or polygonal cells were also observed. By cytochemistry, immunocytochemistry and scanning and transmission electron microscopy, the cells were shown to have characteristics of mesothelial OSE cells in short-term culture. This experimental approach was efficient in providing cultured human OSE, which can be utilized to investigate pathobiology and carcinogenesis. PMID- 7981907 TI - Interactions between normal and tumoral tissues at the boundary of human anterior pituitary adenomas. An immunohistochemical study. AB - We studied the boundary between adenoma and peritumoral anterior pituitary tissues in order to understand their mutual interactions during tumour progression. We selected 18 adenomas of different secretory type, grade and invasiveness in which fragments of peritumoral anterior pituitary were still attached to the adenoma. Immunohistochemistry was performed on serial sections with markers of the basement membranes (type IV collagen), the hormone-producing cells of the normal and neoplastic anterior pituitary, and the folliculo-stellate cells (S-100 protein). In passing from tumour to gland, localized areas of passive compression of the normal gland were seen in only 3 cases. In all the tumours, the boundary consisted partly or solely of a transitional zone characterized by the presence of enlarged cell-cords. Openings in the basement membrane of these enlarged cell-cords were seen in contact with the tumour tissue. Normal and neoplastic cells intermingled in the transitional zone. Normal residual cells could be seen in the central area of the tumour but no adenomatous cells were observed in the gland around the tumour. Folliculo-stellate cells were concentrated in the vicinity of the transition zone. These findings favour the existence of an active process of adenoma expansion within the normal parenchyma, without noticeable infiltration of tumour cells into surrounding gland. PMID- 7981906 TI - The localization of thromboxane synthase in normal and pathological human kidney tissue using a monoclonal antibody Tu 300. AB - Thromboxane, excreted in the urine in increased amounts in glomerular, vascular and tubulo-interstitial diseases, is considered to originate from the kidney. The localization of thromboxane synthase, a key enzyme of arachidonic acid metabolism, was studied in the human kidney by immunohistology using the monoclonal antibody Tu 300. In the interstitial tissue dendritic reticulum cells surrounding the tubules expressed high concentrations of the enzyme. In glomeruli the enzyme was weakly expressed in podocytes. This was confirmed by co localization with an antiserum directed to podocalyxin, a marker of the visceral epithelial cells. In the study of various kidney diseases, massive accumulation of thromboxane synthase containing cells was observed in interstitial diseases, whereas in glomerular diseases there were no differences from normal kidney; in a case of thrombotic microangiopathy podocytes exhibited an increase in thromboxane synthase. The thromboxane-synthase positive infiltrating interstitial cells were shown by conventional light microscopy to be mononuclear phagocytic cells. The physiological sources of renal thromboxane are dendritic reticular cells and podocytes. In interstitial renal disease infiltrating cells of the monocyte/macrophage system constitute the major site of thromboxane synthesis. In glomerular disease, a characteristic alteration of thromboxane-synthase was not found. PMID- 7981908 TI - Tumor cells induced by the v-src oncogene are heterogeneous for expression of markers of mesenchyme differentiation. AB - The observation that v-src-induced tumors contain tumor cells of differing morphology, notably fibroblastoid or polygonal, raised the question as to whether the tumor cells are also heterogeneous with respect to expression of markers of cellular differentiation. Of the markers tested here, consistent reactivity for tumor tissue was noted only for antibody probes reactive to muscle actin (HHF35, alpha sm-1) or to procollagen type I (SP1. D8); for any given tumor, whether induced by v-src DNA or by Rous sarcoma virus, each of these markers was found only in a subpopulation of tumor cells. The observation of marker heterogeneity in the one v-src DNA-induced tumor examined here that typed as monoclonal suggests that v-src-induced transformation is consonant with a degree of plasticity in the phenotypes of the clonal progeny of a single transformant. PMID- 7981911 TI - [Power or authority in the pedagogical relation. What is an act of authority?]. PMID- 7981910 TI - [Power and counter-power in health facilities]. PMID- 7981912 TI - [Authority and management]. PMID- 7981913 TI - [The power of the student]. PMID- 7981909 TI - Electron microscopic evidence of a viral nature for osteoclast inclusions in Paget's disease of bone. AB - Circumstantial evidence from electron microscopic and immunological studies support the view that Paget's disease of bone represents a slow virus infection. However, there is only limited information available regarding its electron microscopic, enzyme and immunocytochemical characteristics. Two cases were studied using electron microscopy with particular emphasis on the inclusions in osteoclasts. Detailed ultrastructural and cytochemical studies including immuno electron microscopy were performed. Some osteoclasts demonstrated specific virus like structures composed of aggregations of microtubules in the nucleus and cytoplasm. The structures were easily digested by trypsin or protease, and were sensitive to RNase, which provided substantial evidence of a proteinaceous nature and inclusion of ribonucleic acid. Immunocytochemical examination identified binding of anti-respiratory syncytial virus and anti-measles virus antibodies in the tissue obtained from one of the two cases examined. The presence of viral antigens in structures in the cytoplasm of Pagetic osteoclasts supports the theory of paramyxovirus involvement in this disease. PMID- 7981915 TI - [Professional recognition?]. PMID- 7981914 TI - [Power, knowledge and liberty]. PMID- 7981916 TI - [A propos of the pedagogical follow-up]. PMID- 7981917 TI - [An experience of learning nursing care in the home]. PMID- 7981918 TI - [You said: "without soul"...]. PMID- 7981919 TI - [Training of nurses' aides and auxiliaries in pediatric nursing]. PMID- 7981920 TI - [Nursing rules: key to the recognition of the proper role]. PMID- 7981921 TI - [Considerations on the stakes of power and authority]. PMID- 7981923 TI - Attitudes of primary care physicians towards the use of a drug formulary- preliminary results of a study in Germany. AB - Although the concept of a drug formulary in primary health care is known for more than 10 years it was only recently that the drug budget of the new German Health Legislation has drawn doctors' attention to the use of such formularies. The loose-leaf form "Gottingen formulary" has been specifically compiled for the need of primary care doctors. It contains less than 300 drugs and drug combinations (including pseudo-placebos). This formulary was ordered by 830 colleagues from November 1992 until the end of May. In June 1993 we sent a semi-structured questionnaire to the users to learn about their experience with and attitude towards the formulary and about changes in their prescribing habits. Until the end of August 223 questionnaires have been returned. Seventy-four % of the respondents were general practitioners with considerable experience (more than 10 years in practice: 77%). The majority were satisfied or very satisfied with the drugs selected for the formulary and found the list helpful or very helpful (68%). Sixty-seven % indicated that the use of the formulary changed their prescribing habits; 70% appreciated an official (governmental) positive list. Although this study did not use a representative sample and the response rate was rather low until the cut-off point, it is noteworthy that the overall appreciation of a drug formulary for primary health care was very positive. The great majority of the respondents were convinced that an individual drug formulary does not render an official positive list superfluous. PMID- 7981922 TI - Lack of pantoprazole drug interactions in man. AB - This review summarizes the results of pharmacokinetic and pharmacodynamic drug interaction studies in man with pantoprazole, a new, selective proton pump inhibitor. Different mechanisms have to be considered as causes for potential drug-drug interactions. Proton pump inhibitors (PPIs) in general may alter the absorption of drugs by increasing the intragastric pH. Due to the presence of an imidazole ring, the PPIs of the class of substituted benzimidazole sulfoxides may interfere with the metabolism of other drugs by altering the activity of drug metabolizing enzymes of the cytochrome P450 system, via either induction or inhibition. With the increasing use of PPIs, their interaction potential gains therapeutic importance as was the case with the first and second generation of H2 blockers (cimetidine and ranitidine, respectively). The enhanced selectivity of pantoprazole to the gastric H+/K(+)-ATPase characterizes the new PPI generation. In comparison to omeprazole and lansoprazole, pantoprazole showed a much lower affinity to cytochrome P450 in vitro and a markedly lower potency in the in vivo rat model for interaction with diazepam. In contrast to omeprazole, pantoprazole does not interact with the cytochrome P450 system in man. In the drug interaction studies conducted so far, pantoprazole did not affect the pharmacokinetics or pharmacodynamics of antipyrine, diazepam, digoxin, a hormonal contraceptive, nifedipine, phenytoin, theophylline and warfarin in man. Also pantoprazole neither induced the drug metabolism of antipyrine nor increased urinary excretion of the induction markers D-glucaric acid and 6 beta-hydroxycortisol. Vice versa, the investigated drugs had no relevant influence on the pharmacokinetics of pantoprazole. PMID- 7981924 TI - Quality control of drug prescriptions by positive lists--the European Formulary. AB - The overall quality of drug prescription is based on three elements: structural, procedural and result quality. In order to improve the clinical outcome (= result quality) of a patient, only drugs with a proven efficacy and a well known risk/benefit-relation should be prescribed. However, in 1992 in Germany, 31.1% of the ambulatory drug prescriptions were for drugs with questionable efficacy or dubious combination preparations. These expenditures therefore cannot be justified, neither from a pharmacological point of view nor from an economic standpoint. One of the main reasons for this poor prescribing quality is a poor structural quality, i.e. too many drugs and lack of transparency on the market and a producer-oriented drug information. In order to improve this structural quality, a drug list will be established by a group of 33 pharmacologists, physicians and pharmacists from 15 European countries. This list aims at 66 diseases, which are thought to be the most common for the general practitioners everyday routine. For these illnesses drug therapies are recommended including information on drug side-effects, possible interactions and contra-indications. Furthermore, basing on published literature, all possible drugs for the 66 indications will be discussed explaining and underlining the choice of the European Formulary Group. However, even a comprehensive drug list may not rule out insufficient procedural quality, i.e. too lengthy prescriptions of benzodiazepines, but may hopefully facilitate the rational choice of drugs and therefore improve patients outcome. PMID- 7981926 TI - Effect of erythropoietin (rHuEPO) on trace elements and quality of life (Qol) in chronic hemodialysis patients. AB - In 30 patients undergoing chronic hemodialysis and whose hematocrit levels had been maintained at 30-50% for 2 years with recombinant human erythropoietin (rHuEPO) administration, changes of serum proteins, serum albumin levels, improvement of trace elements such as zinc (Zn), nickel (Ni) and manganese (Mn), and quality of life (Qol) were examined for 2 years. rHuEPO therapy significantly improved the protein nutritional status, as well as serum Zn, Ni and Mn levels; the concentrations of Zn ion (Zn++), Ni ion (Ni++) and Mn ion (Mn++) in serum were significantly elevated. Objective and subjective Qol of 30 patients showed significant improvement with rHuEPO therapy for 2 years. PMID- 7981925 TI - Tolerability, central effects and pharmacokinetics of intravenous ketorolac tromethamine in volunteers. AB - The central effects, tolerability and pharmacokinetics of multiple intravenous doses of the analgesic ketorolac tromethamine (30 mg 4 times daily for 5 days) were studied in male volunteers. In this double-blind, randomized, parallel group study, 13 subjects received ketorolac tromethamine and 7 subjects received placebo (vehicle). To determine the effects of withdrawal all subjects were then given further dosing with placebo (4 times daily) for 2 days while maintaining the double-blind nature of the previous drug assignment. Physical examinations and laboratory tests were obtained prior to the drug administration and after completion of the study. Scales for assessment of anxiety, depression, sleep and opiate withdrawal were presented to the subjects on day 2, 5, 6, 7 and 8 of the study. After 5 days of multiple intravenous doses ketorolac showed overall good systemic tolerance and safety in comparison with placebo. Myalgia and taste perversion were more frequently reported in the ketorolac group. The frequency of injection site complaints, mostly transient pain, was about 80% for both ketorolac and placebo, indicating these were likely caused by the vehicle. There were no significant changes in the scales assessing anxiety, depression, sleep and opiate withdrawal during treatment with ketorolac and after its withdrawal, suggesting that the drug has neither any major central effects nor any clear addiction potential in this dose schedule. Pharmacokinetic parameters were derived from plasma samples collected after the first and last active doses.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7981927 TI - Staurosporine and its derivatives enhance f-Met-Leu-Phe-induced superoxide production via phospholipase D activation in human polymorphonuclear leukocytes. AB - Staurosporine (STAR) is one of the most potent inhibitors of protein kinase C (PKC). It is known that in human polymorphonuclear leukocytes (PMNs), the phorbol ester-induced generation of superoxide anion (respiratory burst) is effectively inhibited by STAR in a dose-dependent manner, whereas superoxide generation induced by chemoattractants, e.g. n-formyl-methionyl-leucyl-phenylalanine (FMLP) or PAF, is regulated biphasically by STAR. We compared the effects of STAR and K252a on FMLP-induced superoxide production from PMNs and examined the effects of propranolol, a inhibitor of phosphatidic acid (PA) phosphohydrolase, on the potentiation of the production by STAR. We also examined the effects of some derivatives of STAR and K252a on the production and the alteration of the effects induced by propranolol pretreatment. When PMNs were stimulated with FMLP, STAR potentiated superoxide production by 240.5 +/- 30.9% at a low concentration (100 nmol/l). Propranolol pretreatment specifically inhibited the potentiation. When phorbol-12-myristate-13-acetate (PMA) was used as a stimulant, STAR inhibited superoxide production dose-dependently and did not enhance the production. K252a inhibited PMA or FMLP-induced superoxide production dose-dependently and did not enhance FMLP-induced superoxide production. STAR derivatives showed potentiation of FMLP-induced superoxide production similar to that of STAR at concentrations ranging from 10-100 nmol/l, and propranolol (200 mumol/l) effectively inhibited it. K252a derivative NA332 did not show any potentiative effect on the production. PMA-induced superoxide production was inhibited by all compounds dose dependently.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7981928 TI - Binding of colchicine and thiocolchicoside to human serum proteins and blood cells. AB - The binding of 3H-colchicine and its derivative 3H-thiocolchicoside to human serum, purified human proteins and blood cells was studied by equilibrium dialysis and centrifugation. Binding of colchicine and thiocolchicoside to human serum was 38.9 C +/- 4.7 and 12.8 C +/- 5.3%, respectively, essentially to albumin. Protein binding was not dependent on the concentration of either drug between 10(-10) and 10(-5)M. The binding of colchicine and thiocolchicoside to isolated erythrocytes (55 C +/- 5.6 and 16.5 C +/- 2.1%, respectively) decreased markedly in the presence of human serum proteins, i.e. in whole blood (38.7 C +/- 3.1 and 3.4 C +/- 0.8%). Binding of colchicine and thiocolchicoside to other blood cells was very low C < 3%). These binding properties in the blood compartment do not predispose colchicine and thiocolchicoside to be pharmacokinetically sensitive to binding displacement by drug interactions. PMID- 7981929 TI - The efficacy and relative bioavailability of diclofenac resinate in rheumatoid arthritis patients. AB - The pharmacodynamics and pharmacokinetics of 75 mg resin-bound diclofenac (resinate) were compared with enteric-coated tablets containing 75 mg of diclofenac in a double-blind randomized crossover trial in 16 patients suffering from rheumatoid arthritis. Diclofenac was significantly faster absorbed from the resinate than from the enteric coated formulation (tlag = 0.454 h vs. 0.998 h, tmax = 1.41 h vs. 2.56 h) and reached lower peak concentrations (Cmax = 1.64 micrograms/ml vs. 2.59 micrograms/ml). No significant differences were found concerning the area under the plasma level-time curves and the mean residence times. Smaller variances were found for the tmax and the mean residence times in the group treated with diclofenac resinate. Onset and duration of analgesia, as assessed by visual analogue scales were similar in both treatment groups, but did not correlate with the plasma concentrations. Four patients experienced adverse effects including gastric pain, transaminase increases, proteinuria and plasma creatinin increase. No uncommon adverse effects were observed with the new preparation. PMID- 7981930 TI - The effects of cholestyramine and colestipol on the absorption of diclofenac in man. AB - The effect of oral administration of the non-absorbable anion-exchange resins cholestyramine and colestipol hydrochloride on the absorption of diclofenac in man was studied. Adsorption studies in vitro were also performed. In a randomized crossover study consisting of three phases, single doses of water suspensions of colestipol hydrochloride (10 g), or cholestyramine (8 g), or water only were given to six healthy male volunteers immediately following ingestion of diclofenac (100 mg). After dosing, serial blood samples were collected for a period of 8 hours. Plasma harvested from blood was analyzed for diclofenac by a sensitive and accurate high-performance liquid chromatographic method. The area under the plasma concentration-time curve was moderately (33%, p < 0.05) reduced by colestipol, and greatly reduced (62%) by cholestyramine. The maximum plasma concentration was reduced (58%) by colestipol and even more (75%) by cholestyramine treatment. The in-vitro adsorption studies showed that colestipol has a weaker capacity for adsorption of diclofenac compared to cholestyramine. The in-vivo data suggest a reduction of diclofenac bioavailability when colestipol or cholestyramine is administered concomitantly. PMID- 7981931 TI - Quality assurance applied to laparoscopically assisted vaginal hysterectomy: a pilot study. AB - The aim of this quality assurance pilot study was to compare and contrast aspects of hysterectomy for benign conditions using different surgical techniques. Laparoscopically assisted vaginal hysterectomy was compared with abdominal hysterectomy in a private practice setting and was then compared with Browne and Frazer's study of vaginal hysterectomy. Laparoscopic hysterectomy was found to be more costly than abdominal hysterectomy but clients had a reduced hospital stay and earlier return to full activities. The cost of disposable instruments was a major concern and the rationale for their use is questioned. The outcomes and resource allocation implications of the alternatives are considered. PMID- 7981932 TI - Educational interventions and the use of parenteral nutrition. AB - The Georgetown Total Parenteral Nutrition Forum generated consensus statements about the need for nutrition support. The main concern is that the excessive use of parenteral nutritional is both dangerous and expensive. We performed confidential audits using these criteria before and after educational interventions. The incidence of doubtful usage decreased from 29% (8/28) in mid 1991 to 3% (1/30) in mid-1992 (Fisher Exact Probability = 0.01): A post-audit review one year later in mid-1993 revealed an incidence of doubtful usage of 0% (0/19). It is concluded that the consensus document from the Georgetown Parenteral Nutrition Forum is a useful tool for deriving usage guidelines, educating staff and performing criterion audits. In this way, it is possible to generate cost savings and improve the quality of care. PMID- 7981933 TI - Patient dissatisfaction in a paediatric accident and emergency department. AB - This paper presents a review of the patient complaints and those who walked out prior to receiving care in the Accident and Emergency (A&E) Department of the Children's Hospital, Camperdown. The walkout rate was 1.7% (424/27,082) in 1992. Walkouts were greatest in winter when the department was busiest, peak period being between 2000 and 0200 hours. The waiting time was presented as the main reason for walking out. Most parents were prepared to wait the advertised waiting time before leaving. The presenting complaints of children who were not seen covered a spectrum of illnesses with the potential for significant morbidity. The majority, however, were triaged as non-urgent cases. Despite attempts to follow up on walkouts, the outcome for 53% of patients was unknown. Written complaints were fewer in number and tended to focus more on the quality of care (66.6%). There were few recorded compliments. With the increasing customer focus on health, greater attention needs to be given to system failures. PMID- 7981934 TI - Inpatient quality assurance by local analysis of uniform data set data. AB - We constructed a data base in order to examine the profile of patients admitted to a 24 bed inpatient rehabilitation unit at Fairfield Hospital. Data were collected according to the Uniform Data Set for Medical Rehabilitation, and collated and analysed using the Clinical Reporting System database software and the Statistical Package for Interactive Data Analysis statistical software. Outcome data collected included the patients domicile before and after admission, the duration of stay, medical diagnoses before admission to and during the stay in the Rehabilitation Unit, as well as the Functional Independence Measure item scores at admission and discharge. Analysis of the first 100 patients in the data base indicated a duration of stay of 43 +/- 34 days with a right skew distribution. Scatter plots of age and duration of stay, and age and functional improvement showed no bias in the Unit concerning these parameters. The Wilcoxon rank sum test indicated a highly significant difference (P = 0) between entry and exit Functional Independence Measure scores, indicating that patients improved functionally in the unit. Eighty three patients returned home on discharge and only five required admission to a nursing home. With the data base, the course of patients whose performance lies outside the range of normal for the unit can be examined and factors identified which produce a prolonged stay or failure to progress. PMID- 7981935 TI - A survey of persisting leg and/or foot pain in vascular surgery patients. AB - Two surveys were performed on more than 100 postoperative peripheral vascular procedure patients in order to ascertain the incidence and extent of prolonged lower limb pain. There was a significant number of patients who continued to experience moderate or greater degrees of disability associated with their pain at more than 7 months postoperatively. A multidisciplinary approach to the management of peripheral vascular patients is discussed. PMID- 7981936 TI - Evaluating health care: what can hospital separation data tell us about the complications of hospital care? AB - The New South Wales (NSW) Health Department is attempting to refocus the health system towards examination of the outcomes of health interventions. Increased use of existing State-wide databases to measure outcomes of services is an important part of the reorientation of the health system. Complications of hospital care is one indicator of the quality and outcomes of health services. This study analyses surgical complications occurring in NSW residents admitted to hospital during 1989/90. Over 20,000 complications were recorded during this time (corresponding to a rate of 30/1000 surgical procedures). The most common complication recorded was postoperative infection. 71% of complications occurred during a surgical admission, while 29% of complications were associated with a readmission to hospital. While the incidence of complications could be estimated, there were substantial problems with the interpretation of the data which severely limited their potential usefulness. The implications of these results for the ongoing evaluation of the quality and outcomes of hospital care are discussed. PMID- 7981937 TI - Australian Council on Healthcare Standards surveyor recommendations: analysis of compliance in the medical services. AB - This article reports on an analysis of hospitals surveyed by the Australian Council on Healthcare Standards (ACHS) in 1990. The major areas found to require further attention within the medical services were quality assurance processes, mechanisms for appointments and delineation of clinical privileges and some lines of communication with other hospital staff/departments. Similar results also were found in an earlier ACHS analysis of 216 hospitals surveyed 1987-1989. Despite the highlighted areas of concern, 70% of medical services recommendations made at earlier surveys had been fully implemented and 15% partially implemented by hospitals at the time of their next survey in 1990. PMID- 7981938 TI - Chromosomal variation in pocket gophers (Geomys) detected by sequential G-, R-, and C-band analyses. AB - The chromosomes of six taxa, representing five species of Geomys (G. attwateri, G. breviceps, G. personatus, G. texensis, G. bursarius) were analysed for variation in G-band, R-band, sequential R-/DAPI-AMD, and sequential R-/C-band patterns. Eleven chromosomes had structural rearrangements resulting from deletion/addition events. Fission/fusion rearrangements occurred in two chromosomes, and a pericentric inversion was confirmed in only one chromosome. Eighteen of 34 autosomes had constitutive heterochromatin, with variation in its presence or absence, position, and quantity. The heterochromatic differences were seen both among species and between two subspecies of G. personatus. Chromomycin A3 fluorescent staining identified G-C rich regions in 31 of the autosomes with 29 showing variation in their presence or absence, position, and quantity, and identified a high degree of cryptic variation. The X chromosome was highly variable, with differences attributable to structural rearrangements and variation in chromomycin bright-staining regions. PMID- 7981939 TI - Rapidly evolving repetitive DNAs in a conservative genome: a test of factors that affect chromosomal evolution. AB - The hypothesis that tandemly repeated DNA sequences may facilitate chromosomal rearrangements was tested by comparing a conservatively evolving karyotype of a bat species (Macrotus waterhousii) with data published for a rapidly evolving karyotype of an equid species (Equus zebra). Empirical data generated from the phylogenetic screening of rapidly evolving repetitive DNAs from approximately 0.1% of the M. waterhousii genome showed only one sequence that was repetitive in M. waterhousii but low in copy number or absent from the outgroup Artibeus jamaicensis. This compares to 34 such clones containing sequences which were repetitive in E. zebra but were low in copy number or absent from the outgroup Ceratotherium simum. The bat sequence represents a single family of repeated sequences, whereas six families of sequences were identified in E. zebra. Southern blot analysis suggested that the sequence from M. waterhousii is interspersed rather than tandemly repeated, as are the sequences in E. zebra. These data support the above hypothesis and suggest that species with conservatively evolving karyotypes have fewer numbers and families of rapidly evolving DNA sequences than do species such as the equids that possess a karyotype that is considered to have undergone rapid karyotypic evolution. PMID- 7981940 TI - The telochore: a telomeric differentiation of the chromosome axis. AB - We have analysed by means of silver staining the structure of the chromosome axis at the telomeres of meiotic chromosomes in three different grasshopper species. At metaphase I the chromatid axes run the length of the chromatids although they do not reach the chromosome ends. The axes of sister chromatids are associated and show a round differentiation at their distal ends that we have named the 'telochore'. Telochores never contact the chromosome ends: there is always some chromatin beyond them. In late metaphase I bivalents with a distal chiasma, anaphase I and metaphase II half-bivalents and anaphase II chromatids, the axes clearly possess one telochore in each chromosome end. These results seem to indicate that telochores are differentiations of the distal ends of chromatids. We discuss the possible structural significance of telochores according to the current scaffold/radial loop model of chromatin organization of eukaryotic metaphase chromosomes. Additionally, we suggest the possible functional role of the telochore as a nucleoprotein domain forming a protective cap for telomeric DNA. PMID- 7981941 TI - Ultrastructural detection of kinetochores by silver impregnation. AB - We describe a simple silver impregnation method for the ultrastructural detection of kinetochores on meiotic chromosomes of the grasshopper Eyprepocnemis plorans. Testes were fixed with glutaraldehyde and silver-impregnated. After Epon 812 embedding, ultrathin cutting and counterstaining with uranyl acetate, sections were studied by transmission electron microscopy. The meiotic chromosomes showed differentially silver-impregnated 'ball and cup' kinetochores. Some pericentriolar material also showed silver deposits. These observations are discussed in the light of previous results obtained by light microscopy of silver stained spermatocytes in which both kinetochores and pericentriolar material were also preferentially stained. These results suggest a role for acidic proteins in the composition of these structures. PMID- 7981943 TI - Parental genome separation and asynchronous centromere division in interspecific F1 hybrids in Lathyrus. AB - Chromosomes were studied in root-tip metaphase cells of several F1 interspecific Lathyrus hybrids including: L. hirsutus x L. cassius (H x C), L. cassius x L. hirsutus (C x H), L. cassius x L. odoratus (C x O), and their parents, all with 2n = 2x = 14. Two types of morphologically distinct centromeres were identified in the hybrids on the basis of the degree of contraction of the primary constriction. At least 12 well-defined centromeres were seen in all cells of L. hirsutus, L. cassius and L. odoratus, and about 80% of cells had 14. The hybrids were more variable than the species. H x O contained between six and 14 well defined centromeres, while cells of H x C, C x H and C x O all had seven well defined and seven weakly defined centromeres. These were used as markers to plot their spatial disposition in two dimensions on metaphase spreads. In H x C, C x H and C x O the two types of centromeres showed a significant tendency to occupy two spatially distinct and concentrically arranged domains on the metaphase plate (P < 0.005). Owing to shortage of material subsequent work was restricted to H x C and C x H. Six or seven chromosomes of one parental genome were selectively labelled by in situ hybridization using biotinylated total genomic DNA from either parent as a probe. Moreover, there was a very strong correlation between centromere type and genomic origin (P < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7981942 TI - The gene structure of B-type nuclear lamins of Xenopus laevis: implications for the evolution of the vertebrate lamin family. AB - The gene structure of the Xenopus laevis lamin B1 gene is presented, together with a partial analysis of the lamin B2 gene of the same species. The intron/exon pattern of lamin B1 is strikingly similar to other vertebrate lamin genes and is completely identical to that of Xenopus lamin B3. An additional intron present in the murine lamin B2 gene has a counterpart in the orthologue gene of Xenopus. These data complete a comparison of the genomic organization of all vertebrate lamin types known so far. They allow the conclusion that the genes encoding B1 and B3 probably reflect the ancestral lamin gene organization and that the B2 type lamins are derived from them. A non-conforming splice junction sequence is found in the Xenopus lamin B1 gene. A GC is found instead of the canonical GT dinucleotide at the 5' end of intron IX. Comparison with other unusual splice sites indicates that the lamin B1 gene represents a functional gene. PMID- 7981944 TI - Histone H4 acetylated at lysine 16 and proteins of the Drosophila dosage compensation pathway co-localize on the male X chromosome through mitosis. AB - In the fruit fly Drosophila, dosage compensation involves several proteins acting in concert to double the transcriptional activity of genes on the single male X chromosome. Three of these proteins, MLE, MSL-1 and histone H4 acetylated at lysine 16 (H4Ac16), have recently been shown to be located almost exclusively on the male X chromosome in interphase (polytene) cells. We show here that in neuroblasts from third instar Drosophila larvae antisera to H4Ac16, MLE and MSL-1 uniquely label the distal, euchromatic region of the male X chromosome through mitosis. The centromere-proximal, heterochromatic region of the male X is not labelled with these antisera, nor are male autosomes or any chromosomes in female cells. That the association of H4Ac16 with the male X chromosome persists, even when the chromosome is maximally compacted and transcriptionally quiescent, argues that this modified histone is an integral component of the dosage compensation pathway. In the nuclei of interphase neuroblasts from male (but never female) larvae, antibodies to H4Ac16 revealed a small, brightly labelled patch against a background of generally weak nuclear staining. In double labelling experiments, this patch was also labelled, albeit comparatively weakly, with antibodies to MSL-1. These results strongly suggest that the distal, euchromatic region of the X chromosome in male cells occupies a limited and relatively compact nuclear domain. PMID- 7981946 TI - Efficient preparation of plant chromosomes for high-resolution scanning electron microscopy. AB - A highly reproducible technique to prepare plant chromosomes for high-resolution field emission scanning electron microscopy is presented. The procedure allows the production of relatively high numbers of chromosome spreads that can be viewed at high resolution, showing structural details below 10 nm. This preparation technique is not restricted to metaphase chromosomes, but also allows the observation of plant chromosomes during all stages of the cell cycle. PMID- 7981945 TI - The origin of human chromosome 2 analyzed by comparative chromosome mapping with a DNA microlibrary. AB - Fluorescence in situ hybridization (FISH) of microlibraries established from distinct chromosome subregions can test the evolutionary conservation of chromosome bands as well as chromosomal rearrangements that occurred during primate evolution and will help to clarify phylogenetic relationships. We used a DNA library established by microdissection and microcloning from the entire long arm of human chromosome 2 for fluorescence in situ hybridization and comparative mapping of the chromosomes of human, great apes (Pan troglodytes, Pan paniscus, Gorilla gorilla, Pongo pygmaeus) and Old World monkeys (Macaca fuscata and Cercopithecus aethiops). Inversions were found in the pericentric region of the primate chromosome 2p homologs in great apes, and the hybridization pattern demonstrates the known phylogenetically derived telomere fusion in the line that leads to human chromosome 2. The hybridization of the 2q microlibrary to chromosomes of Old World monkeys gave a different pattern from that in the gorilla and the orang-utan, but a pattern similar to that of chimpanzees. This suggests convergence of chromosomal rearrangements in different phylogenetic lines. PMID- 7981947 TI - Cardiovascular disease and hyperlipidaemia. PMID- 7981949 TI - Clinical chemistry and coagulation. PMID- 7981948 TI - Atherosclerosis: cell biology and lipoproteins. PMID- 7981950 TI - Nutrition and therapeutics. PMID- 7981951 TI - Genetics and molecular biology. PMID- 7981952 TI - Lipid metabolism. PMID- 7981953 TI - Cardiovascular disease and hyperlipidaemia. PMID- 7981954 TI - Cardiovascular disease and hyperlipidaemia. PMID- 7981955 TI - Atherosclerosis and arterial influx of lipoproteins. AB - Accumulation of atherogenic lipoproteins in the arterial intima is a key event in the development of atherosclerosis. The likelihood of increased lipoprotein accumulation in the intima increases with increasing influx: arterial influx of lipoproteins is increased by increased arterial wall permeability, increased lipoprotein concentration in plasma, and by high blood pressure. On entrance into the arterial intima, lipoproteins can either efflux as intact particles, be retained in the intima, or be degraded by intimal cells. Increased degradation as well as increased retention of lipoproteins in the intima have both been associated with increased development of atherosclerosis. Therefore, low rates of efflux of intact particles, as appears to be the case for large particles like VLDL, IDL, and possibly lipoprotein (a) could potentially promote atherosclerosis. PMID- 7981957 TI - Antioxidants and atherosclerosis progression: unresolved questions. AB - In animal studies antioxidants have demonstrated antiatherosclerotic actions, but hitherto not in human studies. Prospective epidemiological data suggest that high doses of vitamin E have beneficial effects on major coronary heart disease. Unresolved questions concerning the role of LDL oxidation and antioxidants in atherosclerosis are discussed. It remains to be shown if antioxidants can retard lesion progression in humans, and by what mechanisms they are acting. PMID- 7981956 TI - The mouse as a model for human cardiovascular disease and hyperlipidemia. AB - The mouse has been used as an experimental model for atherosclerosis research for only a short time; however, the sophisticated genetics of this species has resulted in a number of innovative approaches that are not possible with other models. The availability of inbred, congenic, recombinant inbred, and mutant strains has resulted in the discovery of a number of genes affecting atherosclerosis susceptibility. More importantly, the newer genetic technologies such as quantitative trait-loci mapping, transgenic mice, and gene-targeted mice are producing important insights into atherosclerosis. This review, focusing on murine models of cardiovascular disease and hyperlipidemia, will be divided into two parts: naturally occurring models and genetically engineered models. PMID- 7981958 TI - Vascular interactions of lipoprotein (a). AB - Lipoprotein (a) is a major inherited risk factor for vascular diseases, including coronary atherosclerosis, restenosis, and stroke. The pathologic mechanisms are uncertain, but are likely to involve the unique plasminogen-like component of this lipoprotein, apolipoprotein (a). Studies suggest that apolipoprotein (a) can enhance lipid deposition in vessel walls, interfere with fibrinolysis, modulate smooth muscle cell activity, and induce endothelial dysfunction. This review discusses the key concepts relating to these mechanisms, with emphasis on recent studies. PMID- 7981959 TI - Relation of components of insulin resistance syndrome to coronary disease risk. AB - Insulin resistance, which is a prevalent condition, has been associated with a cluster of metabolic disturbances that increase the risk of non-insulin-dependent diabetes mellitus and cardiovascular diseases. In this review article, the complexity of the etiology of insulin resistance is emphasized as it results from the interaction of genetic and environmental factors. Potential cellular defects underlying insulin resistance are discussed as well as the relation of impaired insulin action to dyslipidaemia and coronary heart disease. PMID- 7981960 TI - Antithrombotic therapy in coronary artery disease. AB - Antithrombotic therapy has assumed a central role in the therapy of the acute coronary syndromes and chronic coronary artery disease. The theoretical rationale for antithrombotic therapy, and the established and evolving roles of antiplatelet agents and anticoagulants in coronary disease are reviewed. Emphasis is focused on new antithrombotic agents and novel combinations of existing agents. PMID- 7981961 TI - Isolation and purification of mitochondrial Mn-superoxide dismutase from the gymnosperm Pinus sylvestris L. AB - Manganese superoxide dismutase (Mn-SOD; EC 1.15.1.1) was purified from germinating seeds of Scots pine (Pinus sylvestris L.) 3 days after the start of imbibition. The purification schedule included (NH4)2SO4 fractionation, anion exchange and hydrophobic-interaction chromatographies and chromatofocusing. Purified Mn-SOD had an apparent specific activity of 4,130 McCord-Fridovich units (mg protein)-1. The molecular mass of the holoenzyme was estimated to be 91 kDa by size-exclusion chromatography, and a molecular mass of 23 kDa was determined by SDS-PAGE. However, isoelectric focusing demonstrated that the purified enzyme consisted of three similarly migrating isoforms, with isoelectric points of approximately 6.5. NH2-terminal amino acid sequencing of purified Mn-SOD revealed no differences among the three isoforms. The comparison of the first 32 NH2 terminal amino acids with sequences of NH2-terminal amino acids of Mn-SODs from angiosperms reflected the phylogenetic distances between Scots pine, which is a gymnosperm, and angiospermic species. Cell fractionation suggested the mitochondrial localization of Mn-SODs and no evidence for glyoxysomal localization was found. Mn-SOD activity was absent from dry seeds. It was detectable at a considerable level after imbibition for 24 h, and it was again absent from 3-week-old seedlings. PMID- 7981962 TI - Effects of the degree of polymerization on the binding of xyloglucans to cellulose. AB - Xyloglucan oligosaccharides were isolated with various degrees of polymerization (DP) and reduced with tritiated sodium borohydride. The 3H-oligosaccharides were tested for their ability to bind to amorphous and microcrystalline celluloses and to cellulose filter paper. The time course of binding indicated that the radiolabeled oligosaccharides continued to be bound for at least 1 h after heating at 120 degrees C. The binding probably required the organization of the oligosaccharides and celluloses by gradual annealing after heating. Although neither pentasaccharide (glucose: xylose, 3 : 2), heptasaccharide (glucose : xylose, 4 : 3) and nonsaccharide (glucose : xylose : galactose : fucose, 4 : 3 : 1 : 1) failed to bind to the celluloses, binding occurred with oligosaccharides with DP equivalent to more than four consecutive 1,4-beta-glucosyl residues. The extent of binding to the celluloses increased gradually from octasaccharide (glucose : xylose, 5 : 3) to hendecosanosaccharide (glucose/xylose, 12 : 9), with the increase in the DP of 1,4-beta-glucosyl residues. The binding of reduced cello-dextrins to cellulose required at least 4 consecutive 1,4-beta-glucosyl residues. The extent of binding of cellopentitol or cellohexitol to cellulose was similar to that of hendecosanosaccharide, showing lower binding for xyloglucan oligosaccharides in spite of longer chains of 1,4-beta-glucosyl residues. These findings suggest that the mode of binding to cellulose of xyloglucan oligosaccharides is different from that of cello-oligosaccharides. PMID- 7981963 TI - Functional analysis of the promoters of phenylalanine ammonia-lyase genes in pea. AB - Pycnospore germination fluid of Mycosphaerella pinodes, a fungus pathogenic on pea, contains both an elicitor and a suppressor of the accumulation of pisatin, a major phytoalexin of pea. Transcription of the genes encoding key enzymes in the biosynthesis of pisatin, namely PAL (a gene encoding phenylalanine ammonia-lyase) and CHS (a gene encoding chalcone synthase), was shown to be activated upon the treatment of pea epicotyl tissues with the fungal elicitor and suppressed upon treatment with the fungal suppressor. To investigate the mechanisms underlying activation and suppression of plant defense genes by signal molecules secreted by a fungal pathogen and other stresses, such as ultraviolet (UV) light, we constructed chimeric genes composed of the 5'-flanking regions of two members of the PSPAL family (the genes encoding phenylalanine ammonia-lyase in Pisum sativum) fused to a bacterial gene for chloramphenicol acetyltransferase. Then, the cis-regulatory elements necessary for elicitor-mediated activation and suppressor-mediated suppression were examined in pea protoplasts. Functional analysis of 5' nested deletions of PSPAL1 and PSPAL2 suggested that an enhancer like element is located in the TATA-distal region (-2,196 to -406) in PSPAL2. A cis-acting element(s) responsible for elicitor-mediated activation was found in the TATA-proximal region (-340 to -95 in PSPAL1; -406 to -158 in PSPAL2), in which the consensus sequence motifs known as box 1, box 2 and box 4 [Yamada et al. (1992) Plant Cell Physiol. 33: 715, Lois et al. (1989) EMBO J. 8: 1641] were present in close proximity. Furthermore, both promoters were activated by UV light but were partially suppressed in response to the fungal suppressor. PMID- 7981964 TI - Morphology and microtubule organization in Arabidopsis roots exposed to oryzalin or taxol. AB - In roots of Arabidopsis thaliana, we examined the effects of low concentrations of microtubule inhibitors on the polarity of growth and on the organization of microtubule arrays. Intact 6 d old seedlings were transplanted onto plates containing inhibitors, and sampled 12 h, 24 h and 48 h later. Oryzalin, a compound that causes microtubule depolymerization, stimulates the radial expansion of roots. The amount of radial swelling is linearly proportional to the logarithm of the oryzalin concentration, from the response threshold, 170 nM, to 1 microM. Cells in the zone of division were slightly more sensitive to oryzalin than were cells in the zone of pure elongation. Radial swelling is also stimulated by taxol, a compound that causes microtubule polymerization. Taxol at 1 microM causes little swelling, but at 10 microM causes extensive radial swelling of cells in the elongation zone, and does not affect cells in the division zone. To examine the microtubules in these roots, we used methacrylate sections with immunofluorescence microscopy. At all concentrations of oryzalin, cortical arrays are disorganized and depleted of microtubules, and the microtubules themselves often appear fragmented. These effects increase in severity with concentration, but are unmistakable at 170 nM. In taxol, cortical arrays appear to be more intensely stained than those of controls. At 10 microM, many cells in growing regions of the stele have longitudinal microtubules, whereas many cells in the cortex appear to have transversely aligned microtubules. Taxol affects microtubules in cells of division and elongation zones to the same extent, despite the observed difference in growth.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7981965 TI - Two novel endopeptidases released into the medium during mating of gametes of Chlamydomonas reinhardtii. AB - During the mating reaction between mt+ and mt- gametes of Chlamydomonas reinhardtii, two novel endopeptidases, each of which was able to digest the B chain of insulin, were released into the culture medium, together with a gamete lytic enzyme (GLE) which is responsible for digestion of the gametic cell walls. Both endopeptidases and GLE were copurified from the mating medium by column chromatography on DEAE-cellulose and concanavalin A. Gel filtration separated the peptidases, which were unable to digest gametic cell walls, into two fractions, endopeptidase-1 and endopeptidase-2. These enzymes were also separated from GLE, which was unable to digest the B chain of insulin. Endopeptidase-1, with a molecular mass of about 200 kDa, cleaved the B chain of insulin at the Ala14 Leu15 peptide bond, and this activity was inhibited by EDTA. Endopeptidase-2, with a molecular mass of about 110 kDa, digested the peptide at the Leu15-Tyr16 peptide bond and was sensitive to iodoacetate and chymostatin. When the cell walls of gametes of either mating-type were digested prior to mating with exogenously added GLE, the two endopeptidases were released into the medium, a result that suggests that they are stored, like GLE, outside the plasmalemma. PMID- 7981966 TI - The oligosaccharide units of the xyloglucans in the cell walls of bulbs of onion, garlic and their hybrid. AB - Xyloglucans were isolated from the 24% KOH-soluble fraction of the cell walls of bulbs of onion (Allium cepa), garlic (Allium sativum) and their hybrid. The polysaccharides yielded single peaks upon gel filtration with average molecular weights of 65,000 for onion, 55,000 for garlic and 82,000 for the hybrid. Compositional analysis of the oligosaccharide units after digestion with an endo 1,4-beta-glucanase from Streptomyces indicated that the polysaccharides were constructed of four kinds of repeating oligosaccharide unit, namely, a decasaccharide (glucose/xylose/galactose/fucose, 4 : 3: 2 : 1), a nonasaccharide (glucose/xylose/galactose/fucose, 4 : 3 : 1 : 1), an octasaccharide (glucose/xylose/galactose, 4 : 3 : 1), and a heptasaccharide (glucose/xylose, 4 : 3). The xyloglucan from the hybrid contained highly fucosylated units that resembled those from onion rather than from garlic. The analysis also revealed that the xyloglucans from Allium species contain highly substituted xylosyl residues with fucosyl-galactosyl residues, suggesting that these monocotyledonous plants resemble dicotyledons in the structural features of their xyloglucans. PMID- 7981967 TI - Cytolysins from intracellular pathogens. PMID- 7981968 TI - Plant resistance to rusts and mildews: genetic control and possible mechanisms. AB - Genes in plants that confer race-specific resistance to rusts and mildews are widely exploited in agriculture and can prevent huge losses at little cost. However, nothing is known of the molecular basis of their action. Genetic studies, together with observations of responses at the ultrastructural level, can provide broad insights into how resistance is achieved, which may help in cloning resistance genes. PMID- 7981969 TI - Microbial sialidases: does bigger always mean better? AB - Sialidases are a superfamily of N-acylneuraminate-releasing (sialic-acid releasing) exoglycosidases found mainly in higher eukaryotes and in some, mostly pathogenic, viruses, bacteria and protozoans. The functions of sialidases are poorly understood and, until recently, their biochemical and evolutionary relationships were unclear. A comparative approach has demonstrated the remarkable similarities and differences between nonviral sialidases, and is providing clues about their functions. PMID- 7981970 TI - Host-plant invasion by Rhizobium: the role of cell-surface components. AB - Rhizobia are soil bacteria that can become endosymbionts, reducing atmospheric nitrogen within nodules formed on the roots of legume plants. During tissue and cell invasion, bacterial cell-surface components adapt the bacterium to survive as an endophyte without eliciting host-defence responses. The structures of many of these components have been established recently, allowing their possible roles in invasion to be defined more clearly. PMID- 7981971 TI - Mechanisms of persistence of mycobacteria. AB - Pathogenic mycobacteria use a variety of mechanisms to survive and replicate within mononuclear phagocytic cells, including avoidance of early direct activation of macrophages, interference with gamma-interferon-mediated activation and inhibition of bactericidal products. Developments in genetic manipulation should allow the genes involved in mycobacterial virulence and intracellular survival to be identified. Understanding these mechanisms may lead to more effective treatment and prevention of mycobacterial infections. PMID- 7981972 TI - How to become a pathogen. AB - For most bacterial species, virulence is viewed as a derived state, whereby pathogens acquire certain loci and are rendered virulent. The majority of virulence genes in Salmonella are present in closely related nonpathogenic species, and most genes known to be confined to the salmonellae are not essential for virulence. Alternative evolutionary scenarios may explain the origins of pathogenicity in Salmonella. PMID- 7981973 TI - The HIV-1 nef gene acts as a positive viral infectivity factor. AB - The gene product of the nef gene of HIV-1 acts both to increase the infectivity of viral particles and to reduce the expression of the CD4 receptor molecule on the cell surface. These two functions of Nef may be related, in that downregulation of CD4 may promote the production of HIV that has greater infectivity. PMID- 7981974 TI - Nomenclature of mycobacterial stress proteins (65 kDa antigens) and other members of the Hsp60 family. PMID- 7981975 TI - Effect of insulin and isoproterenol on lipid metabolism in porcine adipose tissue from different depots. AB - Significant differences were found in the rates of lipogenesis, glucose oxidation and lipolysis in porcine adipose tissue from four depots; outer subcutaneous (OSC), middle subcutaneous (MSC), perirenal (PR) and omental (OM). Lipogenesis was stimulated by insulin in all depots in the order PR > OM > MSC > OSC. Lipolysis was stimulated by isoproterenol in all depots in the order PR > OM > MSC > OSC. Differences in lipid metabolism by the different depots may have an important impact on lipid accretion in vivo. PMID- 7981976 TI - In vitro effects of aspirin on malondialdehyde formation and on activity of antioxidant and some metal-containing enzymes. AB - The in vitro effects of aspirin in different concentrations on malondialdehyde formation and on the activity of antioxidant and some metal-containing enzymes in rat liver homogenate and erythrocytes were studied. Aspirin showed a biphasic dependence on concentration: low concentrations (to 1.0 mM) stimulated the spontaneously formed malondialdehyde in the liver homogenate and the high concentration (5.0 mM) inhibited it; all aspirin concentrations tested had no effect on the liposomes; 5.0 mM aspirin inhibited the Fe(2+)-induced lipid peroxidation in the liver homogenate but had an opposite effect on the liposomes. Aspirin dose-dependently inhibited nitro-blue tetrazolium reduction and decreased deoxyribose degradation. The higher aspirin concentrations inhibited the activity of antioxidant and some metal-containing enzymes. It is suggested that these aspirin effects are determined by the aspirin-metal complexes formed rather than by aspirin itself. PMID- 7981978 TI - Disappearance rate of glycosylated and non-glycosylated chicken growth hormone: influence on biological activity. AB - The disappearance rates for glycosylated (GcGH) and non-glycosylated chicken growth hormone (NGcGH) were compared following their intravenous injection into anaesthetized adult laying hens. The metabolic clearance rate of GcGH was about 20% lower (P = 0.13) compared to NGcGH. Similarly, there was a tendency towards a longer half-life for GcGH. No major physiological significance could be attributed to the glycosylation state of the preparations as far as their effects on circulating insulin-like growth factor I and iodohormone levels were concerned. PMID- 7981977 TI - Action of PBAN and related peptides on pheromone biosynthesis in isolated pheromone glands of the redbanded leafroller moth, Argyrotaenia velutinana. AB - Isolated pheromone glands from the redbanded leafroller moth, Argyrotaenia velutinana, were utilized to demonstrate the action of pheromone biosynthesis activating neuropeptide (PBAN) and bursa pheromonotropic peptide plus several other related peptides on pheromone biosynthesis. All peptides belonging to the PBAN family and the bursa peptide stimulated pheromone biosynthesis as measured by pheromone titer and incorporation of radiolabeled acetate. These peptides required the presence of extracellular Ca2+ for expression of full activity and several inorganic Ca2+ channel blockers inhibited the stimulation of pheromone biosynthesis. The Ca2+ ionophore A23187 alone stimulated pheromone biosynthesis as did a cAMP analogue. Stimulation by the cAMP analogue in the absence of extracellular Ca2+ was observed. Maximum pheromone titers were observed in 16 hr gland incubations; however, 2-6 hr incubations were required if pheromone biosynthesis was measured by incorporation of radiolabeled acetate. Radiolabeled glucose incorporation was not increased in the presence of PBAN. These results are discussed in the context of how the pheromone biosynthetic pathway is stimulated by these peptides. PMID- 7981980 TI - Insulin stimulates glycolysis and pentose cycle activity in bovine microvascular endothelial cells. AB - Glucose metabolism via the pentose cycle, glycolysis and the Krebs cycle was quantified in bovine microvascular endothelial cells. The major measured end product of glucose was L-lactate, with relatively small amounts of glucose carbons converted to CO2 and pyruvate. The pentose cycle accounted for less than 4% of the glucose utilized. About 60-70% of the metabolized glucose carbons could not be accounted for by lactate, pyruvate and CO2. Insulin stimulated glycolysis and pentose cycle activity, but had no effect on glucose oxidation via the Krebs cycle. As the pentose cycle is a major source of NADPH which is required for the synthesis of nitric oxide (the endothelium relaxing factor), insulin may play a role in regulating NO generation in endothelial cells by modulating the pentose cycle activity. PMID- 7981979 TI - Identification of protein kinase C-alpha, epsilon and zeta in rabbit ileal enterocytes. AB - Activation of protein kinase C (PKC) has been shown to regulate electrolyte transport in rabbit small intestine. We investigated the types of PKC isoforms in rabbit ileal villus and crypt cells and the potential for phorbol 12-myristate 13 acetate (PMA) to induce translocation of the PKC from the cytosol to the plasma membrane. Our results indicate that there are at least three PKC isoforms, alpha, epsilon and zeta, are present in both villus and crypt enterocytes. Acute treatment with PMA resulted in translocation of the PKC-alpha from the cytosol to the membrane fraction in both cell types. Prolonged exposure of the villus cells to PMA resulted in a significant progressive decrement in PKC-alpha, suggesting down regulation. Since PMA treatment results in translocation, this isoform may be involved in the regulation of electrolyte transport in the rabbit ileum. PMID- 7981982 TI - An endogenous ligand for the kainate-type binding sites from rat brain. AB - Extracts from the rat brain were screened to identify a putative endogenous ligand for the binding sites of the neuroexcitant kainic acid (KA). The extracted substances were separated by chromatographic techniques and tested for their ability to inhibit KA binding to fish synaptosomes and to membranes from rat brain. A substance isolated in this way (rat kainate-binding inhibitor, RKBI) display a competitive interaction with KA for the low-affinity binding sites in rat brain membranes. According to the separation behavior in the purification step, RKBI is distinct from an inhibitor formerly isolated from fish nervous tissue (KBI). The substance exhibits positive co-operativity with KA for a very low-affinity site population, particularly concentrated in the cerebellum, and could play a physiological role in this area. PMID- 7981981 TI - Insecticidal and cytotoxic effects of natural and hemisynthetic destruxins. AB - The insecticidal and cytotoxic effects of 13 natural and hemisynthetic destruxins have been studied. DE shows insecticidal effects similar to those of DA, while DE and DA are more active than all the other natural compounds and analogues tested. Brominated destruxin is a relatively active analogue displaying particular modalities of cytotoxic effects which reflect a certain originality of its mode of action. The linear molecule resulting from the opening of the DA cycle is not toxic. The most hydrophilic destruxins showing e.g. charged radicals (COO-) appear the least toxic probably because they do not penetrate easily the cellular membranes. PMID- 7981984 TI - Serious problems with methotrexate? PMID- 7981983 TI - The effect of the humoral immune system-derived bursal anti-steroidogenic peptide (BASP) on corticosteroid biosynthesis in avian, porcine and canine adrenal cortical cells. AB - Utilizing avian, porcine and canine adrenocortical cells, we have examined the effect of bursal anti-steroidogenic peptide (BASP) on adrenocorticotropin (ACTH) and dibutyryl cyclic AMP (DB-cAMP)-stimulated corticosteroid and cAMP formation. BASP significantly (P < 0.05) suppressed corticosteroid production from adrenocortical cells derived from chickens, pigs and dogs. BASP significantly increased cAMP formation (up to 10-fold) in a dose-related manner. These findings suggest that BASP structure and activity may be conserved between chicken, porcine and canine species. PMID- 7981985 TI - Current rheumatological uses of intravenous immunoglobulin. PMID- 7981986 TI - Genetics of osteoporosis. AB - Identification of the major contribution of genetic factors in determination of peak bone mass at skeletal maturity and possibly on subsequent age-related bone loss has led to efforts to identify possible mechanisms. Recent evidence suggests one mechanism relates to genetic effects on bone turnover mediated via the vitamin D system. This field of research has potential for reducing osteoporotic fracture risk by allowing interventions at different stages in life to reduce this increasing problem of ageing societies. PMID- 7981987 TI - Type I collagen degradation product in serum of patients with early rheumatoid arthritis: relationship to disease activity and radiological progression in a 3 year follow-up. AB - The new assay of cross-linked carboxyterminal telopeptide of type I collagen (ICTP), a serum marker for bone collagen degradation, was evaluated in serial measurements of 66 patients with early RA during a 3-yr prospective study. Initially 51% of RA patients had elevated levels of serum ICTP compared to healthy controls. During the subsequent months after starting anti-rheumatic treatment, the mean ICTP levels decreased in parallel with the clinical and laboratory variables measuring disease activity. Despite marked clinical improvement with anti-rheumatic treatment, a steady increase in radiological progression of joints was observed. Throughout the follow-up serum ICTP levels correlated with inflammatory parameters and from the first year on with the radiological changes assessed annually. However, initial serum ICTP levels correlated better than the other variables of disease activity with the subsequent erosive progression of joints indicating that measurement of serum ICTP may serve as one of the prognostic markers for joint damage in early RA. PMID- 7981988 TI - Circulating concentrations and production of cytokines and soluble receptors in rheumatoid arthritis patients: effects of a single dose methotrexate. AB - Methotrexate (MTX) is an effective treatment for RA and its effects may be partly due to cytokine modulation. Herein, we assessed the effects of a single MTX dose on the production and circulating concentrations of several cytokines and soluble receptors in 42 RA patients on three consecutive days. Three patient groups were studied: (a) 16 patients taking the first MTX dose, (b) 11 patients on chronic MTX treatment and (c) a control group of 15 patients not treated with MTX. Cytokine production was studied in peripheral blood mononuclear cells (PBMNC) and in a whole-blood culture system (WBCS). Group (a) had a more active disease according to laboratory parameters as well as higher circulating IL-6 levels (P = 0.002). The secretion of IL-1 beta by stimulated PBMNC (P = 0.008) was higher in this group and decreased significantly (P = 0.03) after a single MTX dose. No significant change in any parameter was observed after MTX in group (b). In the total patient group, circulating concentrations of IL-1 beta and TNF-alpha were low but blood cells showed a high capacity of production for these cytokines. In contrast for sTNFRs, high circulating levels but a limited in vitro production were observed. In conclusion, a single MTX dose may result in decreased production of IL-1 beta by PBMNC in patients with active RA. Furthermore, we observed an imbalance in the production of TNF-alpha and sTNFRs by peripheral blood cells of RA patients and propose that the WBCS is convenient for studying cytokine production in RA. PMID- 7981989 TI - IgM, IgA and IgG class serum antibodies against Klebsiella pneumoniae and Escherichia coli lipopolysaccharides in patients with ankylosing spondylitis. AB - Igm, IgA and IgG class serum antibodies against Klebsiella pneumoniae and Escherichia coli lipopolysaccharides (LPS) were studied by ELISA in two separate AS patient populations of 99 and 81 subjects and in 102 healthy blood donors. In the first patient population increased levels of IgM and IgG class antibodies against K. pneumoniae LPS were observed in patients with active AS. In the population with active AS, increased levels of IgM, IgA and IgG class antibodies against K. pneumoniae LPS and IgA class antibodies against E. coli LPS were observed. Sulphasalazine treatment decreased IgM and IgA class antibody levels significantly against K. pneumoniae LPS and IgM class antibodies against E. coli LPS. These findings suggest that a significant part of the anti-Klebsiella antibodies found in AS patients is directed against the LPS component of Klebsiella. PMID- 7981990 TI - Intestinal flora in early rheumatoid arthritis. AB - To study the role of intestinal flora in the pathogenesis of RA, we have applied computerized gas-liquid chromatography (GLC) for bacterial cellular fatty acids (CFAs) present in the stool. The CFA spectra represents the total composition of bacterial CFAs in a faecal sample. Correlation and cluster analysis of CFA spectra gathers samples with quantitatively and qualitatively similar bacterial flora into clusters, which then reveal the relationship of samples to each other. Stool samples were collected at the time of hospital admission from patients with early RA before any specific treatment. The CFA spectra in stool samples of RA patients were significantly different from those of non-RA controls. Patients with erosive RA formed a group most clearly different from the controls. Analyses based on the CFA composition of reference bacteria revealed that anaerobic bacteria are primarily responsible for the differences observed. These results suggest that intestinal bacteria play a role in the development of RA. PMID- 7981991 TI - Effect of sulphasalazine on gastrointestinal microflora and on mucosal heat shock protein expression in patients with rheumatoid arthritis. AB - This study was performed in order to elucidate a possible association between mucosal heat shock protein expression, the gastrointestinal microflora and disease activity in 17 patients with RA before and after 16 weeks of sulphasalazine (SASP) treatment. The duodenal-jejunal mucosal binding of the monoclonal antibody ML30, recognizing the 65 kDa heat shock protein of mycobacteria, was increased (P = 0.048) in the untreated RA patients compared to controls, but did not correlate to disease, activity or microflora and was not altered by SASP therapy. There was no convincing evidence for bacterial overgrowth in the jejunum and the faecal microflora was normal. SASP treatment altered the faecal microflora, with significant reductions of the total aerobic bacteria, Escherichia coli and Bacteroides, and increased numbers of Bacillus. SASP had only minor effects on the jejunal microflora. A high carriage frequency of Candida albicans was found in saliva and the counts correlated negatively with the unstimulated whole salivary secretion rate. These results suggest that the gut may be involved in the aetiopathogenesis of RA but do not substantiate the hypothesis that the anti-rheumatic effects of SASP are mediated via its anti microbial properties. However, the possibility that a micro-organism, not detected in this study, may be of crucial importance in RA, cannot be ruled out. PMID- 7981992 TI - Combination of methotrexate and sulphasalazine vs methotrexate alone: a randomized open clinical trial in rheumatoid arthritis patients resistant to sulphasalazine therapy. AB - To compare efficacy, toxicity, and the pharmacokinetics of the combination of sulphasalazine (SASP) and methotrexate (MTX) vs MTX alone in the treatment of SASP-resistant RA we conducted a controlled open clinical trial. Forty RA patients with active arthritis despite adequate SASP therapy, were allocated randomly to regimes of either SASP+MTX or MTX alone. The patients were evaluated openly by a single observer for 24 weeks. In the first 15 patients using the combination, pharmacokinetics of MTX without and with SASP were studied. Thirty eight patients completed the trial. The mean decrease in the disease activity score in the group of patients receiving the combination was significantly greater than in the MTX group (-2.6 vs -1.3 respectively). The same pattern was seen concerning the other efficacy variables. There was no difference in the occurrence of toxicity. SASP had no influence on the pharmacokinetics of MTX. In conclusion in this open study the efficacy of the combination of MTX and SASP seems to be superior to MTX alone, the toxicity of both therapies was similar. This effect was not explained by the pharmacokinetics of MTX which were not altered by concomitant SASP administration. PMID- 7981993 TI - Insufficiency fractures of the distal tibia. AB - Eight patients are described who had sustained insufficiency fractures of the distal tibia, in one case, bilaterally. Seven of the eight patients had RA. Features common to most patients were delay in diagnosis, low body weight, pain and swelling around the ankle joint, steroid therapy, generalized osteopenia and relatively young age. Patients with RA all had ankle joint involvement and impaired mobility. PMID- 7981994 TI - Functional assessment in ankylosing spondylitis: evaluation of a new self administered questionnaire and correlation with anthropometric variables. AB - We describe the development of a new self-administered questionnaire for assessment of specific disability in ankylosing spondylitis (AS). The questionnaire was derived both from discussion with patients and from previous published material and covered four main areas of function: mobility, bending down, reaching up and neck movements, and posture. Four categories of response were available similar to the Stanford Health Assessment Questionnaire and the questionnaire was similarly scored providing a range of scores from 0-3. The questionnaire was found to be acceptable, understandable, easy to complete and fulfilled recognized criteria for reproducibility and validity. A significant improvement in functional score as a result of treatment was found in a longitudinal study of physiotherapy in 42 subjects with AS (pre-treatment score 1.23 +/- 0.79, post-treatment 1.07 +/- 0.75 P < 0.01). The areas which showed the most improvement were mobility, bending and posture. Functional scores correlated well with some anthropometric variables, particularly cervical movements, finger to floor distance and chest expansion. Both spinal and peripheral joint impairment contributed to functional disability. PMID- 7981995 TI - Disease-specific stressors in rheumatoid arthritis: coping and well-being. AB - Results with Coping with Rheumatic Stressors (CORS) are reported. The CORS measures eight coping styles directed at the most important chronic stressors of RA i.e. pain, limitations, and dependence. The relation between coping and well being was analysed while controlling for relevant disease status variables. Comforting cognitions, decreasing activity and diverting attention were styles of coping with pain that were related to well-being, when level of pain was controlled. Optimism, pacing, and seeking creative solutions were styles of coping with limitations. Both optimism and pacing were related to well-being, when functional capacity was being controlled. Acceptance and showing consideration were styles of coping with dependence. Consideration was the only coping style related to well-being, when functional capacity and social network were being controlled. PMID- 7981996 TI - Systemic lupus erythematosus and acute demyelinating polyneuropathy. AB - Guillain-Barre syndrome has been described only rarely in patients with SLE. In this Grand Round we describe a 33-yr-old patient who presented with features of central nervous system lupus, thrombocytopenia, and a severe haemolytic anaemia. Within a few days of her admission, following the commencement of steroid therapy, and a grand mal seizure, the patient developed paralysis of her lower limbs, due to an acute demyelinating polyneuropathy, and subsequently a retinal vasculitis. We discuss the epidemiological and possible immunopathological links between SLE and Guillain-Barre syndrome, and possible treatment strategies. PMID- 7981997 TI - Leg ulceration in rheumatoid arthritis. AB - Chronic leg ulcers occur in 1% of the adult population with considerable associated morbidity, and community costs estimated at up to 600 million pounds p.a. in the UK. Leg ulcers appear to be relatively common in patients with RA and are widely believed to be resistant to treatment. Such ulcers are often attributed to vasculitis, but little is known of the occurrence of other potential aetiological factors. This article reviews the epidemiology, natural history and aetiology of chronic leg ulcers in RA as well as the therapeutic options available. PMID- 7981998 TI - Cryptococcal spondylitis: solitary infective bone lesions are not always tuberculous. AB - Tuberculous spondylitis is a well-recognized cause of back pain and vertebral collapse due to infection and with must not be overlooked even if it is not the most likely diagnosis. If a patient, particularly one of Asian origin, were to present with a solitary destructive bone lesion, without evidence of myeloma or other malignancy, a trial of anti-tuberculous chemotherapy would be one therapeutic approach, even if there was no evidence of tuberculosis elsewhere. However, failure to biopsy the bone lesion and undertake the appropriate microbiology could lead to other important diagnoses being missed. This is illustrated by the case which we report below. PMID- 7981999 TI - Wegener's granulomatosis and CREST syndrome. PMID- 7982000 TI - Special Interest Group for Joint Hypermobility, 20 April 1994, Brighton. PMID- 7982001 TI - Dermatomyositis associated with pneumomediastinum and subcutaneous cellular tissue emphysema. PMID- 7982002 TI - Acute calcific tendinitis of the foot. PMID- 7982003 TI - Large granular lymphocyte expansions in rheumatoid disease. PMID- 7982004 TI - [25 years' of the Slovak Pharmaceutical Society]. PMID- 7982006 TI - [Anti-calcium effects of 4-hydroxypropiophenone derivatives--potential beta adrenoreceptor blockers]. AB - The present paper carries out the pharmacological evaluation of 4-(2-hydroxy-3 isopropylaminopropoxy)-3-(alkoxymethyl) propiophenones with an ethoxy, propoxy and butoxy-group, whose structures are typical of the blockers of beta-adrenergic receptors. In the above-mentioned compounds the anticalcium effect on the frequency and the amplitude and the negative chronotropic and the negative inotropic effects were evaluated by means of the method of spontaneously pulsing guinea-pig atria within a concentration range of 4-16 microgram.cm-3. The obtained results confirmed a significant anticalcium effect on the heart rate in the compounds with a propoxy and a butoxy group, and in the standard verapamil. In all three compounds as well as in the standard verapamil, no anticalcium effect on the amplitude was found. The results of this membrane efficacy are in agreement with the preceding evaluation of the antidysrhythmic and anti isoprenaline activity with the most marked effect in the compound with a propoxy group. On the basis of these results it is possible to conclude that in these derivatives of 4-hydroxypropiophenone also the anticalcium effect can participate, besides the beta-adrenolytic and the membranostabilizing effects, in the antidysrhythmic activity. PMID- 7982005 TI - [Comparison of the effect of selected anticholinergic agents on cholinergic and noncholinergic effects of GV substances during acute poisoning in rats]. AB - In experiments on male rats, the effect of selected cholinolytic agents (atropine, benactyzine, G 3063) in combination with the reactivator of cholinesterases HI-6 on the cholinergic and non-cholinergic effects of GV substance in the course of acute sublethal intoxication was compared. The cholinergic affects of GV substance were examined by means of the changes in the activity of cholinesterases in whole blood, the CNS, diaphragm and liver, the noncholinergic stressogenic effects by means of the changes in the level of corticosterone in plasma and the activity of tyrosine amino transferase in the liver. It follows from the changes in the activity of cholinesterases that the cholinergic effects of GV substance are least influenced by atropine, whereas benactyzine and G 3063 exert an approximately similar effect. The difference in the effect is evident especially in the 24th hour of intoxication. Similarly stressogenic effects of GV substance are least influenced by an antidotal combination of atropine and HI-6. It means that the centrally acting cholinolytic agents benactyzine and G 3063 are more advantageous for the therapy of GV substance poisonings than the peripherally acting atropine. PMID- 7982007 TI - [Radioprotective effects of basic copper carboxylate complexes]. AB - The radioprotective activity of eight selected copper (II) carboxylates--Cu (RCOO)2.nL (R = alkyl, aryl, 2-furyl and 2-thienyl; L usually represents water)- was assayed in a model of lethally gamma-irradiated (9 Gy, 0.97 Gy/min) mice. The compounds tested were applied (as solutions in saline) s.c. in three single doses of 20 mumol/kg 48.24 and 6 h before irradiation. The highest radioprotective effects were measured by survival of mice achieved after premedication of animals with copper (II) 2-thenoate monohydrate (77%), copper (II) acetylsalicylate (64%), copper (II) 2-methoxybenzoate monohydrate (62%) and copper (II) acetate monohydrate (54%). On the other hand, survival of vehicle-pretreated mice was only 10%. The observed biological properties of complexes are discussed in relation to their structures. PMID- 7982008 TI - [Mutagenic activity of copper phenoxyacetate complexes]. AB - The mutagenic activity of phenoxyacetatocopper (II) complexes of the composition Cu(R-COO)2Ln-R = phenoxymethyl, L represents H2O (n = 3), phenazone (1), 4 nitropyridine N-oxide (1)--as well free phenoxyacetic acid and uncoordinated 4 nitropyridine N-oxide was tested against strains of Salmonella typhimurium (TA 100, TA 97 and TA 102) with or without metabolic activation. Using Ames methods in vitro, of the above-mentioned compounds only the 4-nitropyridine N-oxide complex in a concentration of 75 micrograms/dish, with 27.7% content of this neutral ligand) and this molecule ligand alone (in a concentration of 12.5 micrograms/dish) exhibited genotoxic effects. The relationship between the coordination-chemical properties and the biological effects of the compounds tested is discussed. PMID- 7982009 TI - [500 years since the birth of G. Agricola, a physician and pharmacist in Jachymov]. AB - Georgius Agricola (1494-1555) had graduated in medicine and then he chose the mining town of Jachymov as the first place for practicing his profession and became the municipal physician and pharmacist there in 1527. There he wrote his first book on mining as well as a comparative study of ancient measures and weights, necessary for correct preparation of medicines according to the recipes of ancient authors. In 1533 he moved house to the Saxon town of Chemnitz. Besides practicing medicine he dedicated himself to mineralogy and mining, which made him famous. The paper also draws attention to some other writings of his, particularly his treatise on plague (1554). PMID- 7982010 TI - Contributions to the complex study of some lichens-Usnea genus. Pharmacological studies on Usnea barbata and Usnea hirta species. AB - The pharmacological researches have been performed for Usnea barbata and Usnea hirta species using hydroalcoholic extracts. The acute toxicity has been determined and the following LD50 have been obtained: i. p. Usnea barbata 22.53g vegetal material/kg b. w.; Usnea hirta 21.02g vegetal material/kg b. w.; i. v. Usnea barbata 7.43 vegetal material/kg b. w.; Usnea hirta 4.52g vegetal material/kg b. w.; per os up to 32g vegetal material/kg b. w. no mortality has been recorded. It has been demonstrated that the antiinflammatory activity was comparable, sometimes superior to the phenylbutazone and hydrocortisone hemisuccinate; the analgesic activity was close to the noraminophenazone; the antipyretic activity was equal, sometimes superior to the aminophenazone. In Romania, Usnea barbata was mentioned in 1929 among the plants known by Romanian people with popular names: "Bear's beard", "Trees' dandruff", "Woman's long hair" (1). "Farmacia naturii" (2) and "Flora medicinala a Romaniei" (3) have mentioned that Usnea barbata (L) Mott contains usnic acid-substance with broad antibiotic spectrum. Lichens have made the subject of the multiple studies because of their old medical use (4). Besides the antibiotic properties noticed at lichens products (4) there have been discovered the following pharmacological actions: antiinflammatory (5), antitumoural, immunostimulatory (6, 7, 8, 9). The results of the researches made on lichens family within Romania's spontaneous flora (10) have determined us to study the two species: Usnea barbata (L) Mott and Usnea hirta (L) Wigg. PMID- 7982012 TI - EEG study of kainate-induced epilepsy in non-anaesthetized freely moving rats. AB - Epileptogenic activity of kainic acid (KA) was examined by a great number of in vitro studies but few in vivo studies were reported. In the present study, we investigated KA-induced epilepsy by clinical observation and EEG recordings in non-anaesthetized freely moving rats. PMID- 7982011 TI - Heart metabolic modifications induced by nifedipine treatment in normo- and hypertensive Wistar rats. AB - Male Wistar rats weighing 150 +/- 10 g at the beginning of the experiment were used. The animals were divided in to four groups: control group (C); Hypertensive group (H) (Hypertension induced by subcutaneously injecting desoxycorticosterone acetate: 14 mg/kg b. w./day and intragastric tubage administration of 30% sodium chloride: 3 g NaCl/kg b. w./day for 4 weeks); normotensive group receiving Nifedipine (N) (0.5 mg/Kg b. w./day); hypertensive group receiving Nifedipine (HN) (hypertension was induced as in group H and Nifedipine dose was as in group N). We observed that hypertensive status as well as Nifedipine treatment caused an increase of preference of rat heart muscle to utilize its glycogen as carbohydrate energy source instead of added glucose to incubation medium. PMID- 7982014 TI - Voluntary multiplet discharge after the activation test for spasmophilia as an electromyographic sign of a mild form of this disease. AB - The electromyographic (EMG) diagnosis of spasmophilia is based on the appearance in a susceptible muscle of spontaneous burst (multiplet) discharges after an activation procedure consisting usually in 10 minutes ischemia followed by a pause of a length that varies with the author but does not exceed 5 minutes, and finally by a hyperventilation, again not exceeding 5 minutes. In investigations carried out many years ago we observed that a number of subjects with symptoms of spasmophilia showed no postischemic spontaneous bursts, but responded with bursts to voluntary contraction. In this work we present some findings leading to the conclusion that voluntary burst discharge after the activation procedure can represent a sign of spasmophilia and not a mere manifestation within normal limits. Thus, in most cases with no symptoms of spasmophilia, voluntary burst response was absent. On the other hand, most subjects with such an EMG alteration suffered of troubles attributable to spasmophilia. Crisis of tetania with partial or generalized contracture could be encountered in such cases with a frequency close to that of cases with mild spontaneous burst discharge, being, on the contrary, exceptional in cases with normal EMG. In a previous work we showed the existence of a close correlation between the increase above normal of the incidence of ischemic discharge and the intensity of postischemic spontaneous burst (multiplet) discharge. A significant increase of ischemic discharge was also found for the cases showing only voluntary bursts (34.29% of 487 cases as compared to 14.28% of 602 normals). In addition, the period of abnormal burst responses of motor units to voluntary command was significantly prolonged for the cases with more intense ischemic discharge. Finally, there is no gap between spontaneous and voluntary burst discharge, since not rarely a short contraction could trigger a rhythmical selfmaintained burst discharge entirely similar to the spontaneously occurring one. One may conclude that voluntary burst discharges, if rather persistent, can represent a sign of spasmophilic alteration of excitability that must be always tested EMG in suspected cases that give no spontaneous burst discharge to the facilitation procedures. It represents a change in excitability less severe than the spontaneous burst discharge. PMID- 7982013 TI - [Actual preoccupations concerning the cardiac renin-angiotensin system]. PMID- 7982015 TI - The effect of diapulse therapy on the healing of decubitus ulcer. AB - The effect of pulsed high peak power electromagnetic field (Diapulse) on treatment of pressure ulcers is under investigation. 20 elderly patients, aged from 60 to 84, hospitalized with chronic conditions and bearing long-standing pressure ulcers, are subjected to Diapulse sessions (1-2 daily), parallel to conventional treatment. 5 patients undergo conventional therapy, serving as control and 5 others follow conventional+placebo Diapulse treatment. All patients were daily monitored, concerning their clinical status and ulcers' healing. After a maximum 2-weeks treatment, bulge healing rate was, as follows: 85% excellent and 15% very good healing under Diapulse therapy; in the placebo group, 80% patients show no improvement and 20% poor improvement; in the control group, 60% patients show no improvement and 40% poor improvement of ulcers. This investigation strongly advises for Diapulse treatment as a modern, uninvasive therapy of great efficiency and low social costs in resolving a serious, widespread medical problem. PMID- 7982016 TI - Studies regarding some effects of inosine in elite weightlifters. AB - The authors performed a study in 14 top weightlifters, in order to make evident some effects of inosine. The athletes of A group received daily 1.5 g inosine (3 x 500 mg) for 6 weeks while the athletes of the B group (control group) received placebo. Six weeks inosine treatment induced significant changes for serum lipids and FFA (increase), urine mucoproteins (decrease), evoked muscular potential for the right median nerve and motric speed conductibility of the right external sciaticus popliteus nerve; the activity of serum CPK also increased. Some of these changes (CPK, evoked muscular potential, urine mucoproteins etc.) were evident even after 3 weeks of treatment. PMID- 7982017 TI - Study on physiopathology of the chronic psychoorganic syndrome. Investigation on the reactivity of the adrenal glands in patients with psychoorganic chronic. AB - Out of a great number of cases with chronic psychoorganic syndrome studied by us, we have selected, for investigation, a number of 100 cases which presented common symptomatology: a psychosyndrome showing, by a large number of manifestations such as asthenia, fatigability, adynamia with various degrees of intensity building up to reaction latency, diminution or even absence of initiative, basic negativism, tendency to depression with feeling of futility, anxiety, lowered affective tonus. The intellectual activity is largely diminished, the stream of ideas is poor, and there is a limited domain of preoccupations. All these symptoms alongside with somatic, muscular, renal, respiratory, digestive and cardiovascular disorders have led us to the hypothesis of chronic deficiency of the hormones in the adrenal glands. The adrenal glands have been studied by indirect exploration of the hydroelectrolytic metabolism of the peripheral blood, the Thorn test and the Robinson-Power-Kepler test. For the exploration of the glucocorticoids, a basal test has been used such as the 17-hydroxycorticoid test, which measures cortisol elimination, or as the 11-desoxycorticosteroids and metabolites, or the colorimetric Porter-Silber method. Among the dynamic tests, we have used stimulating tests, the ACTH test (synthetic Synachtene), which measures cortisolemia and the 17-urinary corticosteroids, faster and easier than the Thorn test. In order to assess androgens, we have used the ACTH deposit dynamic test (Synachtene retard), which in the case of normal function of the adrenal glands, in 24 hours, doubles the elimination of 17-hydrocorticosteroids, 17-Ketosteroids, D. H. E. A., pregnandiol, pregnantriol.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7982018 TI - [Physiopathological correlations in aminoaciduria and microalbuminuria in diabetic nephropathy]. PMID- 7982019 TI - The effect of pulsed electromagnetic field (Diapulse) on cellular systems. AB - The effect of a 27.12 MHz pulsed electromagnetic field (Diapulse) on microbial growth is investigated. A strain of K 12 E. coli grown in complete Pennassay medium is subjected to Diapulse action for 30 min, at 8 hrs and 12 hrs of growth. In this experimental set-up, designed to be closed to the physiological conditions of open wounds, the Diapulse action does not promote any increase of cell population, indicating the safety of this type of therapy for wound healing process. The same K 12 E. coli strain grown in Pennassay medium for 2 hours is inoculated into a minimal growth medium and the lagless exponential growth thus obtained is followed by a spectrophotometric method. Diapulse field is applied to this lagless phase of cellular cultures at 30, 60, and 90 minutes after inoculation. A slight increase in the number of cells was observed at 2 and 4 hours after the Diapulse application, when the cultures were previously subjected to Diapulse action between the period of 60 and 90 minutes of their growth. A possible molecular mechanism for these effects is discussed. PMID- 7982020 TI - Effects of some benzodiazepines on glycemia in albino rats. AB - The acute administration of some benzodiazepines in normoglycemic rats induced only minor changes of the blood glucose levels. In Triton WR-1339 administered rats, the benzodiazepines brought about minor modifications of this parameter. However, in diabetic rats (streptozotocin-induced diabetes), diazepam administered subacutely elicited very significant diminutions of glycemia. This was due, at least partly, to an increase of the glucose uptake by the skeletal muscle. PMID- 7982021 TI - Romanian contributions to the physiology of the immune response. PMID- 7982022 TI - The ways through which the hypothalamic paraventricular nucleus (PVH) and the medial hypothalamus affect the organism's defence function. AB - In the rats, mechanical lesion or isolation of the PVH either alone or together with the medial hypothalamic sympathetic area, which includes hypophyseotropic area, too, induces a long lasting decrease of the total number of leukocytes and of the most components of the leukocytary formula, which are attributed mainly to the decreased sympathetic tonus, induced by medial hypothalamus disconnection. PMID- 7982023 TI - The effects of leucotrofina or timolimfotropina on some parameters of carbohydrate metabolism in the Wistar rat. AB - A 10 days Leucotrofina or Timolimfotropina administration induced in Wistar rats a rise of glycemia and liver glycogen content, and a decrease of glycogen phosphorylase a activity. These modifications lasted in time and may be due to an activation of the hepatic gluconcogenetic pathway, via a stimulated glucocorticoid production. PMID- 7982024 TI - Effects of leucotrofina and timolimfotropina on the liver of Wistar rats. AB - Adult male rats were treated for 10 days with a thymic extract (Leucotrofina-L, or Timolimfotropina-T, Ellem Milano, Italy), in a daily dose of 0.1 ml/100g body weight. 5 days after the end of the treatment, rats were sacrificed and liver was removed. The modifications in the liver were of the same direction for noth thymic extracts (an increase of the total protein content and of DNA concentration and a decrease of RNA concentration). PMID- 7982025 TI - Immunochemical analysis of some proteins in cerebrospinal fluid and serum of patients with ischemic strokes. AB - Immunochemical studies of gamma gamma-neuron specific enolase (NSE), parvalbumin (PV), S-100 protein (S-100) and acidic fibrillary glial protein (GFAP) were studied in the cerebrospinal fluid and blood serum in 7 patients with ischemic cerebral stroke, aged 57 to 81 years. Cerebrospinal fluid and the first blood sample were taken on the first or second day of the disease. Further blood samples were taken once a week till the end of patients hospitalization, ending by patients discharge or death. Immunochemical identification of proteins under study were performed with Western-blotting technique. It was found that all proteins studied were present in both cerebrospinal fluid and blood serum on the first two days of the disease in small quantities. The blood content of both NSE and PV increased significantly during the first week of the disease. Both proteins disappeared from the blood serum between the second and fourth disease weeks. S-100 protein and GFAP contents in the blood reached significantly high level within the time interval between second and fifth disease weeks, and remained at a relatively high level till patients' death. In all cases computed tomography study and/or brain autopsy revealed extensive ischemic foci localized within areas supplied by the middle cerebral artery. No clear-cut correlation between extensiveness of the ischemic cerebral damage and the content of the proteins studied in both cerebrospinal fluid and blood serum was found. However, our data indicate that serial studies of the above proteins in patients with ischemic stroke may be useful in monitoring the progress of the disease, and occasionally in the prognosis at least in some cases. PMID- 7982026 TI - Ischemia inhibits GABAergic neurons of the rat thalamic reticular nucleus. An immunocytochemical study. AB - GABA-immunoreactivity in the thalamic reticular nucleus was studied in rats subjected to 10 min global cerebral ischemia, due to experimentally induced cardiac arrest. The studies were performed in different postischemic periods (10 min, 1 h and 24 h after ischemia) with postembedding immuno-gold technique for electron microscopy, applying antisera raised against protein-gamma amino butyric acid-conjugates. Transient reduction of gold particles content, indicating GABA appearance and distribution in neuronal perikarya and synaptic terminals, was noticed 10 min and 1 h after ischemia. Reduction of immunoreactivity accompanied ultrastructural abnormalities involving both neurons and synapses and taking the form of severe swelling and disorganization of organelles arrangement. Immunocytochemical abnormalities concerning neuronal perikarya appeared earlier and were more severe. At 24th h after ischemia immunoreactivity of most of the neurons and synapses was similar to this in normal control animals. Morphologically unchanged asymmetric synapses were present in all experimental groups. The presented data confirm high vulnerability of GABAergic neuronal population of the thalamic reticular nucleus to ischemia and suggest transient nature of postischemic GABAergic insufficiency. PMID- 7982027 TI - Myelin lipids and proteins in experimental global ischemia. AB - The experiments were performed on white rats, in which clinical death was induced according to the method described by Korpatchev et al. (1982). After cardiac arrest and cessation of respiratory function lasting 5 minutes resuscitatory action was performed. The lipids and proteins of the cerebral myelin fraction were studied in animals sacrificed 1, 9 and 14 days after global ischemia. The obtained results lead to the following conclusions: 1. Myelin lipids in postreanimation syndrome are characterized by a marked increase in cholesteryl esters and a mild one of lysophosphatidylcholine content. 2. Myelin lipids in the predemyelinating period demonstrate a general pattern of reaction, notwithstanding to the character of the primary noxious agent. 3. After global ischemia a great fall of small basic protein in the myelin fraction and subsequently of SBP to LBP ratio occurred. 4. Various noxious agents affect different proteins of the myelin membranes and the resulting changes seem to be characteristic for various pathological processes. PMID- 7982029 TI - Morphological picture in paroxysmal nocturnal hemoglobinuria. Case report. AB - 25-year-old woman with paroxysmal nocturnal hemoglobinuria was admitted to the hospital because of headache, progressing right hemiparesis and speech disorders. Several days later patient lost consciousness. Cerebrospinal fluid was xanthochromic with increased pleocytosis and protein level. CT-scan revealed ischemic area with hemorrhagic focus within left cerebral hemisphere. Patient died 3 weeks after the admission. Brain section revealed hemorrhagic infarct in the cortex of the left parietal lobe, thrombosis of the superior sagittal sinus and "respiratory brain" changes. Microscopic examination revealed meningeal venous thrombosis, hemorrhagic infarct, vasculitis, abundant accumulation of bacteria within blood vessels, and other pathological changes such as petechiae, perivascular exudates and small, round areas composed of acellular fibrillary network. There were no macrophages and GFAP-positive astrocytes in any of these areas. Authors suggest that weak cell reactivity may be connected with alterations in cell membranes, mainly low phosphatidylinositol (GPI) content. PMID- 7982028 TI - NMDA receptors mediate anoxia/aglycemia-induced release of eicosanoids in immature rat hippocampal slices: utility of an in vitro "ischemic" superfusion model with temporary arrest of medium flow. AB - Hippocampal slices of rats at postnatal day 7 were submitted to superfusion with Ca(2+)- and Mg(2+)-free, bicarbonate buffered ion balanced medium, and perfusate concentrations of eicosanoids: thromboxane B2 and 6-keto prostaglandin F1 alpha were determined by the radioimmunoassay. It was noted that the permanent presence of Ca2+ increased the basal eicosanoid level, and in these conditions modulation of eicosanoid production was lost, whereas temporary, a 20 min application of 1.3 mM Ca2+ did not influence significantly eicosanoid release. A 20 min application of the anoxic/aglycemic medium containing calcium did not change the content of eicosanoids in superfusates. A significant stimulation of the thromboxane B2 and 6-keto prostaglandin F1 alpha release was noted provided the application of the experimental medium was accompanied by a 10 min arrest of superfusion. This effect was inhibited by MK-801 and quinacrine, suggesting an involvement of NMDA receptors and phospholipase A2. We propose that a model of anoxic/aglycemic superfusion with a stop flow period allows retention of endogenous glutamate in the extracellular fluid, resembling a similar effect during in vivo ischemia, whereas during a continuous superfusion glutamate is immediately washed out. Consequently, an application of the anoxic/aglycemic medium accompanied by a temporary arrest of superfusion represents more adequate in vitro model of ischemia than a constant superfusion with this medium. In these conditions NMDA receptors mediate eicosanoid release. PMID- 7982030 TI - Supratentorial astrocytoma associated with arteriovenous malformation. Case report. AB - A case of the 18-year-old boy suffering from epilepsy since 8 years and suspected of microangioma is presented. The craniotomy revealed left parietal parasagittal superficially located neoplasm and arteriovenous malformation beneath. Unexpected fibrillary astrocytoma associated with vascular tumor was the diagnostic problem, solved histologically after the operation. The problem of coexistence of various neoplasms with arteriovenous malformations is discussed. PMID- 7982031 TI - Electron microscopic findings in brain of Rocky Mountain elk with chronic wasting disease. AB - We report here the electron microscopic findings in brain of Rocky Mountain elk with chronic wasting disease (CDW), a progressive and fatal neurological disorder of wild ruminants characterized neuropathologically by intraneuronal vacuolation, spongiform change of the neuropil and astrocytic hypertrophy and hyperplasia. Ultrastructural findings included membrane-bound vacuoles in neuronal elements, increased number of glial filaments, dystrophic neurites, numerous neuritic plaques, Hirano bodies and perikaryal inclusion bodies. Similar findings have been observed in CWD-affected mule deer, as well as in bovine spongiform encephalopathy, and in natural and experimental scrapie and Creutzfeldt-Jakob disease indicating a common etiopathogenesis. PMID- 7982032 TI - A novel structural variant of the human beta 4 integrin cDNA. AB - The ability of the alpha 6 beta 4 integrin to function as a laminin receptor appears to be cell-type dependent. We reported that this integrin functions as a laminin receptor on clone A cells, a colon carcinoma cell line (Lee et al., J. Cell Biol., 117:671-678), but this integrin may not function as a laminin receptor on all cell types in which it is expressed. One potential mode of alpha 6 beta 4 regulation resides in the beta 4 cytoplasmic domain because structural variants of this domain exist. We isolated beta 4 clones from a clone A cDNA library and identified a 21 bp (7aa), in-frame deletion not previously reported. This 7aa variant is located within a region that exhibits a relatively high degree of homology (42%) with the 70aa insert previously reported by Tamura et al. (J. Cell Biol., 111:1593-1604). One major difference between these two regions is that the region we have highlighted does not contain the four potential serine/threonine phosphorylation sites that are present in the 210 bp (70aa) insert. PCR analysis revealed that the 7aa variant is also expressed in RNA obtained from normal colon and placenta. PMID- 7982033 TI - Cloning of five human cadherins clarifies characteristic features of cadherin extracellular domain and provides further evidence for two structurally different types of cadherin. AB - The entire coding sequences for five possible human cadherins, named cadherin-4, 8, -11, -12 and -13, were determined. The deduced amino acid sequences of cadherin-4 and cadherin-13 showed high homology with those of chicken R-cadherin or chicken T-cadherin, suggesting that cadherin-4 and cadherin-13 are mammalian homologues of the chicken R-cadherin or T-cadherin. Comparison of the extracellular domain of these proteins with those of other cadherins and cadherin related proteins clarifies characteristic structural features of this domain. The domain is subdivided into five subdomains, each of which contains a cadherin specific motif characterized by well-conserved amino acid residues and short amino acid sequences. Moreover, each subdomain has unique features of its own. The comparison also provides additional evidence for two structurally different types of cadherins: the first type includes B-, E-, EP-, M, N-, P- and R cadherins and cadherin-4; the second type includes cadherin-5 through cadherin 12. Cadherin-13 lacks the sequence corresponding to the cytoplasmic domain of typical cadherins, but the extracellular domain shares most of the features common to the extracellular domain of cadherins, especially those of the first type of cadherins, suggesting that cadherin-13 is a special type of cadherin. These results, and those of other recent cloning studies, indicate that many cadherins with different properties are expressed in various tissues of different organisms. PMID- 7982034 TI - Evidence for cell surface extracellular matrix binding proteins in Hydra vulgaris. AB - The present study was designed to identify and functionally characterize potential cell surface extracellular matrix binding proteins in Hydra vulgaris. Using [3H]-laminin as a probe, radioreceptor analysis of a dissociated mixed hydra cell preparation indicated that the average number of laminin binding sites per cell was about 10,000 with a dissociation constant of 1.49 nM. These binding sites could be displaced with unlabelled laminin in a dose-dependent manner and with high concentrations (500 nM) of unlabelled fibronectin. No displacement with type-IV collagen and type-I collagen was observed. Immunoscreening studies with a battery of antibodies raised to mammalian extracellular matrix (ECM) binding proteins indicated potential cell surface binding sites for the anti-beta 1 integrin monoclonal antibody, mAb JG22. Cell adhesion studies indicated that mAb JG22 blocked binding of hydra cells to laminin, but did not affect their binding to fibronectin, type-IV collagen, or type-I collagen. Light and electron microscopic immunocytochemical studies indicated that mAb JG22 localized to the basal plasma membrane of ectodermal and endodermal epithelial cells. Immunoprecipitation studies identified tow major bands with masses of about 196 kDa and 150 kDa under reducing conditions, and two bands with masses of > 200 kDa under non-reducing conditions. Functional studies indicated that mAb JG22 could reversibly block morphogenesis of hydra cell aggregates, and could block in vivo interstitial cell migration in hydra grafts. These observations indicate that hydra has cell surface binding sites for ECM components which are functionally important during development of this simple Cnidarian. PMID- 7982035 TI - [In vitro effect of tuftsin (L-prolyl-L-arginine) on the oxidative capacity of polymorphonuclear lymphocytes in small-for-gestational-age newborn infants]. AB - Tuftsin has the function of activating cellular macrophages and polymorphonuclears (PMNs). This tetrapeptide is transported by the CH2 domain of the heavy chain between residues 289 and 292 of the gammaglobulin (IgG) molecule. The objective of this work is to determine the effect of synthetic tuftsin in its oxidative capacity of PMN cells of newborns of low birth weight for their gestational age having already been demonstrated that the phagocytic activity of these cells of macrophages and PMNs is diminished compared with the cells of newborns of normal birth weight according to gestational age. Results showed a stimulatory effect of the PMNs oxidative capacity with synthetic tuftsin by the increase of the nitrotetrazolium blue reduction, demonstrating that the low oxidative capacity of the cells of newborns of low birth weigh for gestational age does not correlate with an intrinsic cellular defect. PMID- 7982036 TI - [Level of knowledge of the technique for using metered-dose inhalers among pediatricians]. AB - A longitudinal open prospective study involving 100 pediatricians from 4 different health institutions was performed. After a written description of inhaler technique was provided and a special questionnaire, physicians were asked to demonstrate the technique using a placebo MDI. Correct use was considered if 10 points were obtained. Thirty pediatricians used MDI in children less than 5 years. The correct written description was observed in 55% (55/100) but 32.7% (18/55) failed to use it properly. Although 45% (45/100) made an incorrect description 25% (25/45) demonstrated a describe previous reports which describe that more than half the physicians ignore the correct steps of inhaler technique. Moreover this lack of information appears to be one of the most important factors which affect self-management of acute and chronic symptoms of asthma in which have contributed to the increased morbidity/mortality of the disease since 1980. PMID- 7982037 TI - [Clinical usefulness of pulse oximetry in asthmatic children]. AB - Abnormalities in exchange and tendency to acidosis and hypoxemia are present in acute asthma. Oxygen arterial saturation (pulse oximetry) is a simple and useful method to evaluate oxygenation conditions. Pulse oximetry and spirometry before and after albuterol nebulization (150 mcg/kg/dose) were performed in 35 subjects. 7 to 14 years, with acute asthma, 68% were mild and the rest moderate. Oxygen saturation before nebulization was less than 90% in 30 children and increased in 27 of them (90%). Spirometry before nebulization showed FEV1 20% predictive values in 18 children and increased in 10 of them. Seven were hospitalized because of worse symptoms. 4 of them showed metabolic acidosis by the presence of lactate. We conclude that pulse oximetry is a useful and simple method for an objective evaluation of acute asthma and its complications, but it is not predictive for a therapeutic decision. PMID- 7982038 TI - [Laboratory findings in allergic diseases]. PMID- 7982039 TI - [Correlation between the concentrations of total serum IgE and skin tests]. AB - An investigation was done to know IgE levels and prick skin test correlation in 300 patients with allergic rhinitis and extrinsic bronchial asthma groups to IgE levels. Correlations themselves contribute to variability index in 15.6% and diagnosis sensitivity in 0.86. We concluded that study (IgE levels) is and indispensable test for atopic patient. PMID- 7982040 TI - [Detection of heterozygotes for ataxia telangiectasia using sensitivity to ionizing radiation]. AB - Recent research have demonstrated that homozygotic and heterozygotic patients with ataxia telangiectasia (AT) show chromosomal rupture. Taking in consideration this characteristic, a study was designed, inducing chromosomal breaks in granulocytes from patients with AT, and heterozygotic carriers of AT compared with a group of healthy individuals. The number of chromosomic ruptures induced by 14 doses of radiation at 125 KV and 125 mA, was measured in all of them. Results suggest significant differences in the number of chromosomal structural alterations induced by radiation in granulocytes from heterozygotic carriers of AT, similar to structural alterations in lymphocytes from patients with AT. It is demonstrated that these alterations occur preferentially in one group C chromosome, both in homozygotic and heterozygotic patients with AT. PMID- 7982041 TI - Evidence that amplification of norepinephrine-induced LH release by morphine is indirectly due to suppression of tuberoinfundibular dopamine secretion. AB - We previously observed that morphine markedly amplifies LH secretion following intracerebroventricular (i.c.v.) norepinephrine (NE) infusions. Based on additional evidence, we hypothesized that perhaps these morphine effects were due to suppression of tuberoinfundibular dopamine (TIDA) secretion thus allowing NE to evoke a greater release of LHRH from axon terminals in the median eminence than would otherwise occur. In the present studies, we examined whether apomorphine (a DA receptor agonist) would suppress and haloperidol (a DA receptor antagonist) would mimic these enhancing effects of morphine on NE-induced LH secretion. Estrogen-treated ovariectomized rats were used in these studies. NE, when infused i.c.v. (45 micrograms) evoked a modest increase in plasma LH (1.1 +/ 0.2 to 2.2 +/- 0.2 ng/ml) within 15 min. When morphine sulfate (10 mg/kg s.c.) was given 15 min prior to NE, LH peak values of 11 +/- 2 ng/ml were obtained by 60 min. Treatment of rats with apomorphine (1.5 mg/kg s.c.) at -15 min, morphine at 0 min and i.c.v. NE at 15 min resulted in a significant blunting of morphine's effect on NE-induced LH release. Moreover, in all morphine-treated rats, plasma prolactin (PRL) increased significantly within 10 min, peaked at 30 min and declined towards basal values by 90 min. Apomorphine completely blocked this morphine effect of PRL release. Haloperidol (HAL; 2.5 mg/kg s.c.) treatment had no effect on basal LH release but resulted in a significant increase in PRL which remained elevated up to 180 min.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7982042 TI - Lipopolysaccharide intracerebral administration induces minimal inflammatory reaction in rat brain. AB - An inflammatory reaction, essential for defence against infection and for wound repair, may also induce irreversible tissue damage. It appears that the central nervous system has developed its own immunosuppressive strategy in order to limit the destructive effects of inflammation. To clarify this point, we have characterized in one unique model of inflammation induced in the rat by intracerebral lipopolysaccharide injection the kinetics of the inflammatory reaction, the participation of immunitary and glial cells and of three growth factors. Among these molecules, brain-derived neurotrophic factor mRNA expression was found decreased following LPS injection. No striking differences were observed in the brain parenchyma after stab lesion or inflammatory lesion apart from an increase in the number of monocytes/macrophages recruited early to the lesion area. Macrophages were later accumulated around the lesion when astroglia and microglia reactions occurred. Some of the macrophages and microglia expressed major histocompatibility complex class II antigens on their surface whereas no T or B lymphocytes were observed in the brain parenchyma. However, a subpopulation of CD3- and CD4-negative CD8-positive cells, likely natural killer cells, was observed around the lesion site; this recruitment was inhibited by the highest dose of LPS. This study therefore supports the hypothesis of a suppression of some aspects of cell-mediated immunity in the brain, mechanisms which need to be further characterized. PMID- 7982043 TI - Mechanisms of hyperpolarization induced by two cytokines, hTNF alpha and hIL-1 alpha in neurons of the mollusc, Onchidium. AB - The voltage and current responses induced by extracellular tumor necrosis factor (hTNF alpha) or interleukin-1 (hIL-1 alpha) on the Be-1 and Es-1 neurons of the Onchidium ganglia were examined. Pressure-ejected hTNF alpha or hIL-1 alpha produced an inhibitory, hyperpolarized effect in unclamped neurons. In the same neurons voltage-clamped at their resting potential levels, the same hTNF alpha or hIL-1 alpha elicited an outward current having a time course similar to that of the hyperpolarization, associated with a decreased membrane conductance. The hTNF alpha- or hIL-1 alpha-induced outward current did not reverse even at positive membrane potentials considerably above + 100 mV in the absence ouabain (a specific blocker of Na-pump). In the presence of ouabain, the hTNF alpha- or hIL 1 alpha-induced current was reduced over a wide range of membrane potential, so that the current reversed at about + 20 mV. Lowering the external Na+ concentration from 450 to 200 mM in the presence of ouabain, shifted the reversal potential from + 20 to 0 mV, to near the shift value of 20.8 mV predicted by the Nernst equation for a Na(+)-selective conductance. Neither an increase nor a decrease of extracellular K+, Cl- or Ca2+, however, significantly altered the current induced by hTNF alpha or hIL-1 alpha. These suggest that the hTNF alpha- or hIL-1 alpha-induced hyperpolarization or outward current response is mediated by two mechanisms, a decrease in Na+ conductance and activation of the Na-pump. PMID- 7982044 TI - Different types of bombesin receptors on neurons in the dorsal raphe nucleus and the rostral hypothalamus in rat brain slices in vitro. AB - The actions of the peptides bombesin (BN), gastrin releasing peptide (GRP), neuromedin C (NMC), litorin and neuromedin B (NMB) were studied on neurons in slices of rat brain maintained in vitro to determine the BN receptor type present in different brain areas. Intracellular and extracellular recordings were made from hypothalamic neurons on the border of the periventricular nucleus (PVN) and suprachiasmatic nucleus (SCN) and from mesencephalic 5-HT sensitive neurons in the dorsal raphe nucleus. In the region of the brain containing the SCN and PVN, BN and the BN-related peptides excited 31 out of 77 neurons on which they were tested. There was little difference in the potency of the BN-related peptides as excitants of neurons, the EC50 being about 10 nM. The response to the peptides usually lasted between 5 and 15 min with little sign of desensitization. Using NMC, GRP and NMB as agonists, the equilibrium constant for the GRP receptor antagonist [D-Phe6]-BN-(6-13)-ethylamide was approximately 10 nM. The response to the peptides fully recovered on washout of the antagonist. The CCKB/gastrin receptor antagonist CI-988 (1 microM) had no effect on either GRP- or NMC mediated excitation. In the dorsal nucleus 40 of 75 neurons were sensitive to the BN-related peptides. BN, [Tyr4]-BN, NMB and litorin, were 10-20 times more potent than GRP and NMC. The responses to the BN-related peptides were not blocked by the selective GRP receptor antagonists [D-Phe6]-BN-(6-13)-methylester, [DF5Phe6][D-Ala11]-BN-(6-13)-methylester and [D-Phe6]-BN-(6-13)- ethylamide.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7982045 TI - Anticonvulsant activity of antagonists and partial agonists for the NMDA receptor associated glycine site in the kindling model of epilepsy. AB - Several previous studies have shown that competitive and uncompetitive N-methyl-D aspartate (NMDA) receptor antagonists are ineffective as anticonvulsants in fully amygdala kindled rats, i.e. a widely-used model of complex-partial seizures (limbic epilepsy). In the present experiments, different categories of ligands for the NMDA receptor-associated glycine modulatory site were evaluated in the kindling model in rats. For this purpose, the 'silent' glycine antagonist 7 chlorokynurenic acid (7-CKA), the low efficacy glycine partial agonist (+)-HA-966 (R(+)-3-amino-1-hydroxypyrrolid- 2-one), and the high efficacy glycine partial agonist D-cycloserine (D-CS) were used. In view of the poor brain penetration of some of these compounds after systemic administration, all drugs were injected bilaterally into the lateral ventricles of fully kindled rat. Anticonvulsant activity was evaluated by determination of the threshold for induction of focal afterdischarges in the amygdala (ADT) and by monitoring seizure parameters (seizure severity, seizure duration, afterdischarge duration) at ADT current. In addition to anticonvulsant activity, the behavioural adverse effects of test drugs were determined. All three drugs increased the focal seizure threshold, although at different potencies. In terms of injected dosages and percentage ADT increase, the most potent compound was 7-CKA, followed by (+)-HA-966 and D-CS. None of the drugs induced behavioural adverse effects or motor impairment (measured in the rotarod test) at anticonvulsant doses. However, D-CS produced proconvulsant effects at higher doses. The data demonstrate that pharmacological manipulation of the glycine modulatory site of the NMDA receptor is an effective means of increasing seizure threshold in amygdala-kindled rats.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7982046 TI - Cerebral mitochondrial redox states during metabolic stress in the immature rat. AB - The brain mitochondrial NAD+/NADH ratio, as a reflection of the oxidation reduction (redox) state of cellular compartment, was determined under conditions of hypoxia, anoxia, hypoxia-ischemia, complete ischemia and hypoglycemia in immature rats. NAD+/NADH ratios were calculated from changes in the concentrations of specific oxidative substrates and calculated intracellular pH during cerebral metabolic stress. The results suggest that the use of the acetoacetate/beta-hydroxybutyrate substrate couple provides a more accurate prediction of the mitochondrial redox state under adverse conditions than use of the alpha-ketoglutarate/glutamate couple. It is possible that the mitochondrial oxidation seen with the latter substrate couple during cerebral metabolic stress might reflect a population of cells (neurons or glia) which are substrate deprived relative to the rest of the brain in the setting of metabolic stress produced by oxygen deficiency. PMID- 7982047 TI - Calcium and cAMP mediated stimulation of Fos in cultured hypothalamic tyrosine hydroxylase-immunoreactive neurons. AB - Immediate-early genes, such as c-fos, couple extracellular signals to genetic changes in the cell. We have previously demonstrated that depolarization with 50 mM KCl increases Fos immunoreactivity in hypothalamic tyrosine hydroxylase (TH) and oxytocin immunoreactive (-ir) neurons in primary culture. This Fos activation occurs within 1.5-2 h in TH-ir cells. In the present study, we examined the effects of depolarization, glutamate receptor activation and adenylyl cyclase stimulation on Fos-ir to determine the possible mechanism(s) of Fos activation in TH-ir neurons. Hypothalamic cultures were treated with KCl, glutamate or forskolin, and Fos and TH were visualized immunocytochemically. Forskolin increased the percentage of Fos/TH-ir neurons in a dose-dependent manner, with a maximal stimulation of 53.4 +/- 4.5% Fos/TH-ir neurons at 30 microM forskolin. The dose-response curve for glutamate was steep, with a maximal stimulation of 24.8 +/- 2.1% Fos-ir neurons at 100 microM. 50 mM KCl resulted in 50.0 +/- 0.8% Fos/TH-ir neurons. Pretreatment with verapamil decreased KCl induced Fos-ir by 57%, glutamate by 65% and forskolin by 39%. Combined drug administration demonstrated significant additivity between forskolin and glutamate, and forskolin and KCl, however, no significant additivity was found with KCl and glutamate. The results are discussed in terms of cAMP and calcium mediation of the Fos response to these stimuli. PMID- 7982049 TI - Developmental changes in the sensitivity of the neonatal rat brain to hypoxic/ischemic injury. AB - Developmental changes in the response of the neonatal rat brain to hypoxic/ischemic injury were examined. Hypoxic/ischemic injury was produced by unilateral carotid ligation followed by exposure to hypoxia in 1- (D1), 3- (D3), 5- (D5) and 7-day-old (D7) rats. Injury was produced in most D7 animals exposed to > or = 120 min of 7.6 or 8% oxygen after carotid ligation. The extent of neuronal injury was variable, ranging from focal neuronal death to massive infarction. In D5 and D3 animals, there was a progressive decline in the extent of neuronal injury in response to hypoxia/ischemia. In the younger animals, bilateral injury was occasionally seen. Sham-operated animals exposed to hypoxia alone had numbers of karyorrhectic neurons similar to normal control animals in all age groups. The underlying developmental changes which account for these differences are not yet known but are likely to be multiple. PMID- 7982048 TI - Mu-opiate receptor binding is up-regulated in mice selectively bred for high stress-induced analgesia. AB - Pain perception and sensitivity to opiate analgesics strongly depend on genotype. Mice selectively bred for high (HA) and low (LA) swim stress-induced analgesia display markedly divergent morphine analgesia, a difference that appears to be determined by one or at the most two major genes. In an attempt to provide candidate genes mediating the supranormal analgesia displayed by HA mice, we performed mu-opiate receptor binding on 27th generation HA, LA, and control (C) mice using [3H]naloxone. HA mice were found to have significantly higher whole brain receptor density (Bmax) than LA mice in whole brain homogenates; no significant difference in affinity (Kd) was observed. Quantitative autoradiography confirmed the line difference in whole-brain receptor binding. In the medial thalamus, a brain area implicated in ascending pathways of pain inhibition, HA mice were found to display significantly higher [3H]naloxone binding than C mice (a 64% increase) and LA mice (a 128% increase). No significant line differences were observed in any other brain locus. Thalamic mu receptors may therefore play an important role in a central 'volume control' mechanism of pain inhibition, and underlie individual differences in the responses of mice to opiate analgesic drugs. PMID- 7982050 TI - Stimulation of synaptosomal Na+,K(+)-ATPase by ethanol: possible involvement of an isozyme-specific inhibitor of Na+,K(+)-ATPase. AB - In synaptosomal preparations from rat cerebral cortex, ouabain-sensitive Rb+ uptake was stimulated by ethanol (20-80 mM). Based on differential sensitivity to ouabain, 80% of this Na+,K(+)-ATPase activity represented activity of the alpha 1 isozyme while 20% was due to the alpha 2 and/or alpha 3 isozymes (alpha 2/ alpha 3). Stimulation of Na+,K(+)-ATPase was selective for the activity of alpha 2/alpha 3 which was increased by 167% in the presence of 80 mM ethanol. In this concentration range, ethanol had no effect on alpha 1 activity. Exposure of synaptosomal preparations to EGTA increased basal (no ethanol) alpha 2/alpha 3 activity with no effect on alpha 1 activity. Further, ethanol no longer stimulated alpha 2/alpha 3 activity after EGTA treatment. An EGTA extract was concentrated and desalted to yield a fraction that selectively inhibited alpha 2/alpha 3 activity when reconstituted with EGTA-treated synaptosomal preparations. This inhibition was trypsin-sensitive, suggesting protein involvement, and was prevented by 80 mM ethanol. In the presence of the inhibitory protein fraction, ethanol stimulated Na+, K(+)-ATPase activity in EGTA treated membranes with a dose-response like that observed with the crude (no EGTA) synaptosomes. We propose that the alpha 2/alpha 3 activity of Na+,K(+) ATPase is subject to inhibitory regulation and that ethanol stimulates this activity by releasing it from inhibition, an effect that may mimic in vivo deregulation of the enzyme by ethanol. PMID- 7982051 TI - Postnatal maturation of the layer III pyramidal neurons in the human prefrontal cortex: a quantitative Golgi analysis. AB - In this study we examined the morphological maturation of the basal dendritic field of layer III pyramidal neurons located in the human dorsolateral prefrontal cortex in subjects ranging from 7.5 months after birth up to 27 years. The sections were stained with the Golgi-Cox method and the three-dimensional branching pattern was measured with a semi-automatic dendrite measuring system. Results show a rapid growth phase of the dendritic field from 7.5 months after birth up to one year. A marked increase in total dendritic length is observed, for which elongation of the terminal segments, longer intermediate segments and an increase in number of segments is an explanation. The dendritic length appears to have stabilized after one year, leading us to conclude that the postnatal morphological maturation of the layer III pyramidals does not continue well into childhood, but is completed at a much younger age. Additionally we analyzed the effect of varying section thickness on dendritic parameters and found no tendency for higher dendritic values with increasing section thickness for the range of thickness values of the histological sections used. PMID- 7982052 TI - Induction of HSP70 mRNA and HSP70 protein in the hippocampus of the developing gerbil following transient forebrain ischemia. AB - The effects of a 20-min transient episode of forebrain ischemia on the induction of HSP70 mRNA and protein, and the histopathological outcome in the hippocampus of the developing gerbil, were examined at postnatal days (P) 7, 15, 21 and 30 and in adulthood. 4 days after the ischemic episode, P7 gerbils did not show apparent histological abnormalities; however, from P15 onwards, ischemia resulted in necrosis in selected areas of the hippocampus. At P15 and P21, necrosis was observed in the base of the granular cell layer of the dentate gyrus and in the CA3 pyramidal cell layer, whereas at P30 and adult necrosis was apparent in the CA1 pyramidal cell layer. HSP70 mRNA induction was not found in ischemic P7 and P15 gerbils while, from P21 onwards, induction was observed in the dentate gyrus and CA1 pyramidal cell layer. In addition, at P30 and adult, HSP70 mRNA expression was also seen in CA3 pyramidal cell layer. Induction of HSP70 immunoreactivity was not seen at P7 but, from P15 onwards, ischemia induced HSP70 immunoreactivity in different areas: in dentate gyrus granular and molecular layers, from P15 onwards; in CA1 pyramidal cell layer, from P21 onwards; and in CA3 pyramidal cell layer, from P30 onwards. Results show selective age-dependent patterns of vulnerability to ischemia in the gerbil hippocampus which, overall, were not well-correlated to the corresponding HSP70 mRNA and protein induction patterns. PMID- 7982054 TI - Effects of neuropeptide Y on short-term memory. AB - Neuropeptide Y (NPY) is a ubiquitous neuropeptide which may modulate several behavioral and physiological phenomena. Among other behavioral effects, NPY has been shown to enhance memory processes in mice. The current study employed a delayed conditional discrimination procedure to evaluate the effects of intracerebroventricular injections of NPY on short-term working memory. This conditional discrimination procedure assesses appropriate responding, based on a previously presented stimulus, after various delays have been imposed between the stimulus and the opportunity for a response. Delay values ranged from 0.01 s to 30 s. NPY decreased accuracy across delay values in a dose-dependent manner. The two highest doses of NPY (3.0 and 10.0 micrograms) significantly decreased accuracy. Doses lower than those used in the current study have shown facilitation of memory processes under avoidance procedures in mice. Intraperitoneal naloxone (3.0 mg/kg), an opioid antagonist, completely blocked NPY's memory degrading effects. Procedural differences may account for NPY induced degradation of short-term working memory under delayed conditional discrimination and previous reports of NPY's enhancement of retention under shock avoidance procedures. PMID- 7982053 TI - Rapid postmortem changes in the cellular localisation of amino acid transmitters in the retina as assessed by immunocytochemistry. AB - We have assessed by means of immunocytochemistry, the cellular distributions of the amino acid transmitters GABA, glycine and glutamate, and the free-radical scavenger taurine, in the retinae of adult rabbits at various times after death. Within 10 min of death, horizontal cells began to display immunoreactivity for GABA, whilst displaced amacrine cells began to display immunoreactivity for glycine. By 40 min postmortem, GABA was present in glial cells. Glutamate, which is not normally detectable in retinal glia, was detected in such glia by 20 min postmortem. By contrast immunocytochemically detectable glycine did not accumulate in glia. There was a gradual diminution of immunoreactivity for taurine in glial cells and photoreceptors. By 2 h postmortem, most immunoreactivity had disappeared from the retina. We conclude that amino acid transmitters show rapid changes in their distributions immediately after death, which may be related to changes in the patterns of transmitter release and uptake, and changes in degradation mechanisms. The rapid changes in cellular localisation of amino acid immunoreactivity illustrated in this study, indicate that the fixation of nervous tissues must be performed rapidly. Moreover, the massive loss of immunoreactivity by 2 h postmortem suggests that any assays for content of these transmitters at this, and subsequent time-points, will bear little resemblance to the values obtained at the time of death. PMID- 7982055 TI - The immunocytochemical localization of glutamate in the electrosensory system of the gymnotiform fish, Apteronotus leptorhynchus. AB - The first processing station of the electrosensory system is the medullary electrosensory lateral line lobe. The electrosensory lateral line lobe of gymnotiform fish is a laminated structure with three anatomically distinct excitatory inputs: primary afferents from electroreceptors, the direct feedback from n. praeminentialis and indirect feedback from n. praeminentialis via a cerebellar lobe--the eminentia granularis posterior. We utilized immunocytochemistry on L-R White-embedded semithin sections, and immunogold on thin sections to localize glutamate and aspartate in the electrosensory lateral line lobe, its afferent inputs and efferent targets. The excitatory inputs and the electrosensory lateral line lobe projection neurons are immunopositive for glutamate only, suggesting that glutamate rather than aspartate is the excitatory transmitter of the electrosensory system. PMID- 7982056 TI - Progressive cognitive impairment following chronic cerebral hypoperfusion induced by permanent occlusion of bilateral carotid arteries in rats. AB - The effects of chronic cerebral hypoperfusion induced by permanent occlusion of bilateral common carotid arteries (2VO) on learning and memory performance were examined in rats using an eight-arm radial maze task. The learning of the task was severely impaired in the permanent 2VO rats that had not been pretrained, while the retention was slightly impaired and soon recovered in the permanent 2VO rats that had been fully pretrained when tested within 1 month after the 2VO operation. The performance, however, was impaired in the pretrained rats when a 3 min delay was interposed between the fourth and fifth choices. Moreover, when retrained in the radial maze 4 months after the permanent 2VO, these same rats showed a performance impairment. Some loss of the hippocampal pyramidal neurons was observed 1 month after the permanent 2VO, although the decrease was not significant. However, significant loss of the cells was observed in the hippocampus CA1 subfield 4 months after the operation. We concluded that: (1) In the early stage (1 month after permanent 2VO), a learning deficit was observed in the non-pretrained rats. In the pretrained rats, working memory was not impaired, whereas longer term memory was compromised; (2) in the late stage (4 months after permanent 2VO), working memory may have also been impaired in the pretrained rats; and (3) this progressive cognitive deficit seemed to parallel the progress of neuronal damage. PMID- 7982057 TI - Altered GABAergic effects on kainic acid-induced seizures in the presence of hippocampal sclerosis in rats. AB - Although deficient inhibitory action of GABAergic neurons is frequently implicated in the pathogenesis of epileptic seizures, their exact contribution to the epileptogenicity is still controversial. In the present study, we investigated the effects of GABAergic action on kainic acid (KA)-induced hippocampal seizure in rats with or without hippocampal sclerosis (HS). HS was produced by pretreatment of KA (12 mg/kg i.p.) 3 weeks prior to induction of acute KA seizure (8 mg/kg i.p.). After development of epileptiform activity in the hippocampus, either muscimol (50 ng/microliters, 1.0 microliter) or vehicle (phosphate buffer solution, 1.0 microliter) was applied locally in the left dorsal hippocampus through a cannula and electrobehavioral observation was performed continuously for 6 h. The seizures were divided into four stages according to their severity. 7 days after the induction of acute seizure, the rats were sacrificed and subjected to histological examinations. In the rats without HS, muscimol reduced the seizure severity as well as neuronal damage, whereas muscimol facilitated the severity of both indicators in the presence of HS. Muscimol accelerated the propagation of epileptiform activity and the onset of more advanced seizure stages regardless of presence or absence of HS. Our study suggest that the GABAa function has dual effects on the final severity of KA-induced seizure depending on the presence or absence of HS and that it accelerates the rate of seizure development in either condition. The altered GABAa function in the presence of HS would probably modify seizure activity. PMID- 7982058 TI - HSP72 induction by heat stress in human neurons and glial cells in culture. AB - Expression of 72-kDa heat shock protein (HSP72) induced by heat stress was investigated in cultured neurons and glial cells isolated from fetal human brains using immunoblotting and immunocytochemistry. Under the unstressed condition, a low level of HSP72 expression was observed in astrocytes, microglia, oligodendrocytes, and neurons. Under the heat-stressed condition, an increased expression of HSP72 was observed in all cell types with specific location in the nuclear and cytoplasmic regions. Following heat stress, HSP72 was expressed intensely in more than 50% of astrocytes and microglia during 8-24 h post recovery, while it was detectable in only 9% of oligodendrocytes and 3% of neurons at 48 h post-recovery. These results indicate that heat stress induces a predominant expression of HSP72 in astrocytes and microglia, and more limited HSP72 expression in oligodendrocytes and neurons in fetal human neural cells in culture. The differential patterns of HSP72 induction in human neural cells by heat stress suggest that cellular mechanisms by which the heat shock response is regulated are different among various cell types in the human central nervous system. PMID- 7982059 TI - Neuroanatomical distribution of receptors for a novel voltage-sensitive calcium channel antagonist, SNX-230 (omega-conopeptide MVIIC). AB - Neuronal voltage-sensitive calcium channels (VSCCs) are a diverse family of proteins that regulate entry of Ca2+ into neurons. Selective antagonists of VSCCs have proven to be powerful pharmacological tools for identifying and characterizing these channels. A new VSCC antagonist, SNX-230 (also known as omega-conopeptide MVIIC), binds with high affinity to receptors in rat brain and blocks one or more high-threshold VSCCs that are neither L- nor N-type. We have defined the neuroanatomical distribution of the high-affinity non-L, non-N VSCC receptors for SNX-230 using [125I]SNX-230 bound to rat brain sections and compared it with that of [125I]SNX-111, a reversible blocker of N-type VSCCs. Highest densities of binding for both ligands were seen in areas rich in synaptic connections, such as the oriens, radiatum and molecular layers of the hippocampus. In general, the density of [125I]SNX-230-binding was higher in cerebellum compared with that in forebrain. In contrast, this general distribution of density was reversed for [125I]SNX-111. In the glomeruli of the olfactory bulb, binding of [125I]SNX-230 was undetectable compared with the high density of [125I]SNX-111-binding. Differential localization of the two ligands was also seen in cervical spinal cord. The clearly different localization of [125I]SNX-230 compared with that of [125I]SNX-111 in the olfactory bulb and spinal cord suggested that the binding sites for [125I]SNX-230 in other brain regions, while co-localized macroscopically, are also distinct from those for [125I]SNX-111. This was confirmed when addition of saturating concentrations of SNX-111 did not affect the distribution pattern of [125I]SNX-230 binding.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7982060 TI - Differential role of histamine in mediating stress-induced changes in central dopaminergic neuronal activity in the rat. AB - The role of histamine in mediating restraint stress-induced alterations in dopaminergic neuronal activity and alpha-melanocyte-stimulating hormone (alpha MSH) secretion was evaluated in male rats. Dopaminergic neuronal activity was estimated by measuring concentrations of the dopamine metabolite 3,4 dihydroxyphenylacetic acid (DOPAC) in brain regions containing terminals of these neurons. Physical restraint increased DOPAC concentrations in nucleus accumbens and decreased DOPAC concentrations in the intermediate lobe of the pituitary, but was without effect on DOPAC concentrations in either the striatum or median eminence. These data indicate that restraint stress increases mesolimbic, decreases periventricular-hypophysial, and is without effect on nigrostriatal or tuberoinfundibular dopaminergic neuronal activity. Neither depletion of neuronal histamine by alpha-fluoromethylhistidine, blockade of H1 receptors by mepyramine, nor blockade of H2 receptors by zolantidine prevented the stress-induced increase in DOPAC concentrations in the nucleus accumbens suggesting that histaminergic neurons are not major contributors to stress-induced increases in mesolimbic dopaminergic neuronal activity. In contrast, alpha-fluoromethylhistidine- and mepyramine-, but not zolantidine-treatment prevented the stress-induced decrease in DOPAC concentrations in the intermediate lobe. Restraint stress increased alpha MSH secretion; this increase was not prevented by alpha fluoromethylhistidine, mepyramine, or zolantidine. These data indicate that histaminergic neurons mediate the stress-induced decrease in periventricular hypophysial dopaminergic neuronal activity through an action at H1 receptors, but do not effect stress-induced alpha MSH secretion. PMID- 7982061 TI - Histaminergic neurons mediate restraint stress-induced increases in the activity of noradrenergic neurons projecting to the hypothalamus. AB - The role of histamine in mediating restraint stress-induced increases in the activity of noradrenergic neurons projecting to the hypothalamus was evaluated in male rats. Noradrenergic neuronal activity was estimated by measuring concentrations of the norepinephrine metabolite 3-methoxy-4 hydroxyphenylethyleneglycol (MHPG) in the paraventricular and medial preoptic nuclei which contain terminals of these neurons. Placement of rats within restraining tubes rapidly increased MHPG but not norepinephrine concentrations in the paraventricular and medial preoptic nuclei. Depletion of neuronal histamine by alpha-fluoromethylhistidine and antagonism of H1 receptors by mepyramine attenuated, whereas blockade of H2 receptors by zolantidine did not prevent the stress-induced increases in MHPG concentrations. Neither mepyramine nor zolantidine affected MHPG concentrations in hypothalamic regions of nonstressed rats. These results indicate that histaminergic neurons contribute to the stress induced increase the activity of noradrenergic neurons projecting to the hypothalamus via an action at H1 receptors. PMID- 7982062 TI - Self-administered nicotine activates the mesolimbic dopamine system through the ventral tegmental area. AB - Microinfusions of the nicotinic antagonist dihydro-beta-erythroidine (DH beta E) were used to examine the role of the mesolimbic dopamine system in nicotine reinforcement in rats. Infusions of DH beta E into the ventral tegmental area (VTA) prior to the start of i.v. nicotine self-administration sessions resulted in a significant decrease in the number of nicotine infusions voluntarily obtained. In contrast, the same doses of DH beta E infused into the nucleus accumbens were without effect on nicotine self-administration. The reductions caused by DH beta E were specific to nicotine reinforcement; neither operant responding maintained by food, cocaine self-administration, or spontaneous locomotor activity were altered by local applications of DH beta E within the VTA. The reduction in nicotine self-administration following treatment in the VTA was also specific to the nicotinic antagonist, and was not duplicated by infusions of the muscarinic antagonist atropine. Partial lesions of the pedunculopontine tegmental nucleus, the likely origin of cholinergic fibers to the VTA, were without effect on nicotine self-administration, suggesting that the effects of DH beta E were not due to disruption of a tonically active cholinergic input to the VTA from this source. These data show that nicotine acts within the VTA region to initiate processes which are critical to the reinforcing properties of the drug. PMID- 7982063 TI - Facilitatory effects of testosterone on hypothalamic tachykinin levels and release. AB - We have reported earlier that central administration of tachykinins profoundly altered the release of pituitary LH and the direction of the LH response was modulated by gonadal steroids in male rats. To further understand the relationship between androgens and hypothalamic tachykinins, we have examined the effects of castration and of testosterone (T)-replacement on levels of Neurokinin A-like immunoreactivity (NKA-li) in microdissected regions of the rat hypothalamus and on in vitro release of hypothalamic NKA-li. Results showed that castration decreased NKA-li levels specifically in the median eminence (ME) and arcuate (ARC) regions as compared to those in intact rats. T replacement immediately following castration prevented these site-specific decreases in NKA li. Similarly, basal efflux of NKA-li was significantly reduced from the entire medial basal hypothalamus (including the ME and ARC) and preoptic area (POA) of castrated rats vs. that from the hypothalami of intact and T-replaced castrated rats. These results show that T can modulate levels of NKA-li selectively in sites previously implicated in the control of LH release and since NKA can inhibit LH and hypothalamic LH-releasing hormone (LHRH) release, these observations are in accord with our view that afferents to LHRH neurons are the targets of gonadal steroid feedback on pituitary LH release. PMID- 7982064 TI - Opening of the blood-brain barrier during cortical superfusion with histamine. AB - Histamine may influence cerebral microcirculation from the intravascular and parenchymal side. The latter route can be simulated by cortical superfusion. The effect of cortical superfusion with histamine (10(-9)-10(-3) M) on blood-brain barrier (BBB) permeability was studied in the cat by measuring extravasation of the tracers Na(+)-fluorescein (MW 376) or fluorescein isothiocyanate (FITC) labelled dextran (MW 62,000 or 145,000) by intravital fluorescence microscopy. Histamine induced an opening of BBB resulting in extravasation of small and large molecular weight tracers with threshold concentrations of 10(-9), 10(-8) and 10( 6) M for Na(+)-fluorescein, FITC-dextran 62,000 and 145,000, respectively. Once tracer extravasation had started the degree of extravasation increased with increasing concentrations of histamine in the superfusion fluid. Similar to histamine the H2 agonist impromidine (3 x 10(-12)-3 x 10(-9) M) induced a concentration dependent extravasation of Na(+)-fluorescein. 2-Pyridylethylamine which is 3-4 times more selective for H1 than for H2 receptors also induced an extravasation of Na(+)-fluorescein. Cortical superfusion with mepyramine (10(-7) M) or cimetidine (10(-4) M), which block the H1 and H2 receptors, respectively, already induced significant extravasation of Na(+)-fluorescein by themselves. These compounds could thus not be used as competitive antagonists to block histamine-induced extravasation. However, our data are in accord with data obtained during intravascular and topical application of histamine and support the hypothesis that H2 receptors at the luminal and abluminal membrane of the endothelium mediate the opening of the BBB.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7982065 TI - The astrocyte mitogen, tumor necrosis factor-alpha, inhibits the proliferative effect of more potent adult human astrocyte mitogens, gamma-interferon and activated T-lymphocyte supernatants. AB - The proliferative response of adult human astrocytes to tumor necrosis factor alpha (TNF-alpha) was examined. Applied alone, TNF-alpha was dependent on the content of serum in the feeding medium, being mitogenic only in conditions of over 15% serum in medium. In accordance with previous results, supernatants from activated human CD8+ T-lymphocytes (CD8 SN) and recombinant human interferon gamma (IFN-gamma) enhanced proliferation of adult human astrocytes in 5% serum containing medium. Simultaneous administration of TNF-alpha (10-1000 units), however, abrogated the mitogenic effects of either CD8 SN or IFN-gamma; the inhibitory effect of TNF-alpha was lost if applied 2 days following IFN-gamma treatment. These studies show that while TNF-alpha is an astrocyte mitogen under selected conditions, it inhibits proliferation induced by other mitogens. In this manner, TNF-alpha may be important in regulating the proliferative response of astrocytes during reactive astrogliosis in vivo. PMID- 7982066 TI - Identification of neural pathways activated in dehydrated rats by means of Fos immunohistochemistry and neural tracing. AB - The distribution of Fos-immunoreactivity (Fos-IR) was studied in the brains of rats deprived of water for 24 or 48 h and compared with that in brains of water replete rats. Intense Fos-IR was observed in many neurons of the median preoptic nucleus (MnPO), organum vasculosum of the lamina terminalis (OVLT), supraoptic nucleus and hypothalamic paraventricular nucleus. There was less intense and sparse Fos-IR in the subfornical organ. In water-replete rats, Fos-IR was absent or very low in these regions. In other rats, cholera toxin B-gold conjugate was microinjected bilaterally into the supraoptic nucleus to identify retrogradely labelled neurons in the lamina terminalis projecting to the supraoptic nucleus. Approximately 30% of these retrogradely labelled neurons in the OVLT and MnPO also exhibited Fos-IR after 48 h of water deprivation. These data show that neurons in the MnPO, OVLT and, to a lesser extent, the subfornical organ probably play an important role in homeostatic responses to dehydration, such as vasopressin secretion. PMID- 7982067 TI - The control of jaw-opener motoneurons during active sleep. AB - Brainstem and spinal cord motoneurons that innervate somatic musculature serving antigravity functions are postsynaptically inhibited during active sleep. However, it has been reported that hypoglossal motoneurons (which do not innervate antigravity muscles) are not postsynaptically inhibited during active sleep, but are disfacilitated. In the present report we describe changes, during active sleep, in the excitability and membrane potential of digastric and synergistic motoneurons of the trigeminal motor pool; these neurons do not perform antigravity functions. The experiments described in the present report were performed in chronic cats that were prepared for intracellular recording. The motoneurons hyperpolarized an average of 11 mV (S.D. +/- 1.29, n = 8, P < 0.005) during active sleep compared to quiet sleep. Hyperpolarization was accompanied by a reduction in the excitability of the somadendritic regions of the neurons, as indicated by an increase in the delay of propagation of antidromic spikes from the initial segment to the somadendritic portion of the cell. High gain membrane potential recordings from these motoneurons revealed the occurrence of a remarkably large number of hyperpolarizing potentials during active sleep. When K-chloride-filled microelectrodes were utilized and chloride ions were injected intracellularly, the polarity of these potentials was reversed. During phasic episodes of active sleep, there was a clear increase in hyperpolarizing potential activity, a blockade of somadendritic spikes and phasic reductions in the amplitude of the initial segment spikes. Hyperpolarizing potentials occurred in conjunction with ponto-geniculo-occipital waves.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7982068 TI - The saturated response of vertebrate rods and its relation to cGMP metabolism. AB - Strong light flashes saturate the response of a rod, and increasing flash intensities prolong the period of saturation. We have found that the period of saturation lengthens from base to tip of the outer segment and we have shown that free cGMP is replenished locally to terminate saturation and not in the G-cyclase rich axonemal region near the inner segment which contains the cell mitochondria. Our results also show that each section of outer segment acts as an independent module in this phase of transduction. PMID- 7982069 TI - Uptake of exogenous fluorescent Di-I by intact junctional epithelium of adult rats allows retrograde labeling of trigeminal sensory neurons. AB - Junctional epithelium (JE) is the special attachment tissue between gingiva and teeth, and it is well innervated by sensory nerve fibers. We have found that the fluorescent carbocyanine dye, Di-I, can penetrate quickly into intact JE and spread into connective tissue. Di-I containing neurons in trigeminal ganglion were found at 3-7 days and were mostly gone by 3 weeks. We conclude that substances such as Di-I can penetrate through permeable epithelia such as intact JE where they are picked up by sensory nerve fibers and carried to nerve cell bodies. PMID- 7982070 TI - cAMP-dependent differential regulation of extracellular matrix (ECM) gene expression in cultured rat Schwann cells. AB - cAMP-dependent regulation of the steady-state mRNA levels for the ECM components, laminin A, B1 and B2 chains, collagen types I, III and IV were examined by Northern blot analysis in cultured rat Schwann cells. ECM mRNAs of laminin B1 chain and collagen types I and IV were expressed at high levels in the control Schwann cells, while laminin B2 chain and collagen type III mRNA levels were low, and laminin A chain mRNA was not detectable. When Schwann cells were treated with forskolin or cAMP derivatives, the gene expression for the ECM molecules constituting the Schwann cell basement membrane, laminin B1 and B2 chains, and collagen type IV, was enhanced in time- and dose-dependent manners for exogenously administered forskolin or cAMP derivatives, while the mRNA levels for the ECM molecules, which are not the major components of the basement membrane, fibrillary collagen types I and III were significantly suppressed. This cAMP dependent differential regulation of Schwann cell ECM gene expression may be related to the role of each ECM molecule in the peripheral nerve development and regeneration. PMID- 7982071 TI - Epileptic activity can induce both long-lasting potentiation and long-lasting depression. AB - Epileptic seizures are associated with massive changes of intracellular ion concentrations which could cause persistent changes in efficacy of afferent excitation. Such alterations were investigated in the CA1 area of hippocampal slices using the acute high potassium model of epilepsy which allows rapid wash of the epileptogenic solution. Field potentials elicited by stimulation of Schaffer collaterals were recorded in stratum pyramidale and stratum radiatum. The experiments revealed that long-lasting potentiation as well as long-lasting depression of field potentials could result from superfusion with high potassium. These changes were NMDA-dependent, but did not depend on the discharge type (interictal vs. ictal) of the slice. It is concluded that epileptic activity cannot only lead to an enhancement of responses to afferent excitation, but also to a long-lasting depression. This depression could represent a self-protective mechanism of the brain which may also be involved in post-ictal depression of cerebral activity. PMID- 7982072 TI - Visual corticogeniculate projections in the cat. AB - The anterograde axonal tracer Biocytin was injected into areas 17-19 of the cat visual cortex to determine the nature of the corticofugal projection from each area to the dorsal lateral geniculate nucleus (LGNd). Each projection had extremely fine terminal branches with even finer twigs that ended in single synaptic boutons. The terminal contacts of the projections from areas 17 and 18 extended throughout the LGNd while those from area 19 were found only in the A1 and CMAG laminae. Unlike earlier experiments, where injections were made into the optic radiations, no beaded axons were found, which adds support to the proposal that such fibres originate from the perigeniculate nucleus rather than the visual cortex. Within the LGNd, fibres of large calibre appeared only to arise from retrogradely labelled cells. All fibres of cortical origin were fine in diameter although there was a higher density of boutons contacting LGNd cell bodies for the area 17 terminals. The recurring fineness of the corticofugal projections indicates that corticofugal signals travel much more slowly than their geniculo cortical counterparts while the greater bouton density of the area 17 projections points to a more independent effect from this cortical area. PMID- 7982073 TI - Traumatic brain injury causes a decrease in M2 muscarinic cholinergic receptor binding in the rat brain. AB - Numerous studies indicate that an acute, excessive activation of muscarinic acetylcholine receptors (mAChR) contributes to the pathophysiological sequela of TBI. The present study examined the effect of moderate fluid percussion traumatic brain injury (TBI) on binding to M1 and M2 mAChR subtypes in the hippocampal formation and adjacent cortex using quantitative autoradiography. Injured animals along with concurrent controls were sacrificed by in situ freezing at 3 h or 24 h following TBI. Slide-mounted tissue sections were incubated in either [3H]pirenzepine (23 nM) for M1 or [3H]AFDX384 (9 nM) for M2 mAChR subtype labeling. Binding of [3H]pirenzepine to the M1 mAChR subtype was not significantly altered by TBI when compared to sham-injured animals. [3H]AFDX384 binding to the M2 mAChR subtype was significantly decreased at 24 h in hippocampal CA2-3 region and dorsal blade of the dentate gyrus (P < 0.05). The differences observed between M1 and M2 subtypes suggests that these muscarinic subtypes may differentially contribute to the pathophysiology of TBI. PMID- 7982074 TI - Protective effect of alpha-tocopherol on brain cell membrane function during cerebral cortical hypoxia in newborn piglets. AB - Protective effect of alpha-tocopherol on the structure and function of brain cell membranes was investigated by measuring Na+,K(+)-ATPase activity and products of lipid peroxidation (fluorescent compounds) in brain cell membranes obtained from newborn piglets. Four groups of anesthetized, ventilated piglets were studied: five hypoxic piglets and five normoxic piglets were pretreated with free alpha tocopherol (20 mg/kg/dose i.m.), five additional hypoxic piglets received i.m. placebo and five normoxic piglets served as control. Placebo and alpha-tocopherol were given 48 and 3 h prior to onset of hypoxia. Hypoxic hypoxia was induced and cerebral hypoxia was documented as a decrease in the ratio of phosphocreatine to inorganic phosphate (PCr/P(i)) using 31P NMR spectroscopy. PCr/P(i) decreased from baseline of 2.62 +/- 0.54 to 1.05 +/- 0.27 in alpha-tocopherol-pretreated and from 2.44 +/- 0.48 to 1.14 +/- 0.30 in the placebo-pretreated group during hypoxia. Na+,K(+)-ATPase activity was unchanged in both normoxic and hypoxic alpha-tocopherol-pretreated groups. However, in placebo-pretreated hypoxic group, Na+,K(+)-ATPase activity decreased as compared with control (44.9 +/- 9.7 vs. 61.8 +/- 5.7 mumol P(i)/mg protein/h, P < 0.005). The level of fluorescent compounds increased in placebo-pretreated but not in alpha-tocopherol-pretreated group as compared with control. During hypoxia, serum alpha-tocopherol levels were higher in alpha-tocopherol-pretreated groups as compared with placebo pretreated hypoxic group. The present data indicates that alpha-tocopherol protects brain cell membranes in newborn piglets from lipid peroxidative damage during tissue hypoxia probably by being incorporated in cell membrane and also as circulating antioxidant. PMID- 7982075 TI - Reactivity to novelty during youth as a predictive factor of cognitive impairment in the elderly: a longitudinal study in rats. AB - A life-span study of certain behavioral traits was conducted in rats. Animals were repeatedly tested in a circular corridor for reactivity to novelty and in a recognition memory task for cognitive abilities. These measures revealed important inter-individual differences in young as well as in old subjects. Some of these differences appear with aging (memory deficits) and others disappear (high reactivity to novelty). Moreover, a relationship between high reactivity to novelty in youth and deficits in memory recognition in elderly was found. Rats that are high-responders to novelty had age-related memory impairments whereas the low-responder rats did not. While the biological mechanism linking these two behavioral traits remains to be demonstrated, this study shows that age-related impairments can be predicted by factors detectable early in life. PMID- 7982076 TI - Amphetamine induces excess release of striatal acetylcholine in vivo that is independent of nigrostriatal dopamine. AB - The effect of amphetamine on striatal acetylcholine (ACh) release was studied by an in vivo intrastriatal microdialysis technique. Although we expected systemic amphetamine to inhibit baseline striatal ACh release, the opposite was found. In addition, we found that the amphetamine-induced striatal ACh release did not depend on nigrostriatal DA since 6-hydroxydopamine (6-OHDA) lesions had no effect on amphetamine-induced ACh release. Local intrastriatal injection of amphetamine via the microdialysis probe had no effect on striatal ACh release even when the probe was located more laterally in striatum to take advantage of the medial to lateral gradient of striatal ACh and D2 receptors. The hypothesis that amphetamine increased extracellular striatal ACh by increasing the release of biogenic amines besides dopamine was tested by pharmacological manipulations designed to specifically increase local striatal norepinephrine or serotonin levels. The serotonergic and noradrenergic manipulations had no effect on striatal ACh levels. These results indicate that amphetamine-induced release of ACh in striatum is mediated via distal brain regions that are functionally connected with the striatum. PMID- 7982077 TI - Antioxidant enzymes in the brain of zitter rats: abnormal metabolism of oxygen species and its relevance to pathogenic changes in the brain of zitter rats with genetic spongiform encephalopathy. AB - Zitter rats develop a genetic spongiform encephalopathy characterized by edematous changes in their brains. In order to elucidate the involvement of reactive oxygen species in this process we examined age-related alterations of the activities of the enzymes which metabolize reactive oxygen species. Activities of superoxide dismutase (SOD), D-amino acid oxidase (D-AAO), glutathione peroxidase (GSH-Px) and catalase in the brain and the liver of zitter rats are compared with those of control SD/J rats. In the brain of adult zitter rats which show degenerative changes, significantly enhanced activities of SOD and D-AAO were obtained, whereas activity of catalase was lower than that of the SD/J rats. Prominent abnormalities in catalase and D-AAO but not in SOD activity were demonstrated before or at the same time as the appearance of the morphological vacuolation in the brain of suckling zitter rats. There was no difference in GSH-Px activity between the brains from zitter and SD/J rats. These results suggest that the alteration of hydrogen peroxide (H2O2)-metabolism in microperoxisomes may play an important role in the initiation of degenerative changes in the brain of zitter rats. Enhanced SOD activity observed in the brain of adult zitter rats may be a compensatory response to the high superoxide anion produced in the course of cell damage caused by the H2O2 stagnation. Also, more SOD might produce more H2O2. PMID- 7982078 TI - Cholinergic and GABAergic septo-hippocampal projection neurons in mice: a retrograde tracing study combined with double immunocytochemistry for choline acetyltransferase and parvalbumin. AB - The present experiments were directed to determine the proportions of the cholinergic and GABAergic septo-hippocampal projection neurons in NMRI mice. For the labeling of the septal neurons we used a double immunocytochemical method combined with retrograde transport of wheatgerm agglutinin apo-horseradish peroxidase-gold (WAHG) injected unilaterally into the hippocampus. Monoclonal antibodies against choline acetyltransferase (ChAT) and parvalbumin (PARV) were used as markers for cholinergic and GABAergic neurons in the medial septum/diagonal band complex (MS/DB). Both antibodies were visualized in the same section using the ABC detection system with diaminobenzidine and 4-chloro-1 naphtol as chromogens. Cholinergic and PARV-containing neurons are coexisting in the MS/DB. About 38% of all retrogradely labeled neurons were ChAT-positive whereas only 10% of all retrogradely labeled cells were immunostained for PARV. On the other hand, 40% of all ChAT-positive neurons and about 24% of all PARV positive neurons were retrogradely labeled. No double immunolabeled neurons were detected. The proportion of GABAergic neurons may have been underestimated because immunostaining for PARV only labels a subpopulation of GABAergic neurons. The present results were compared with those of previous studies in rats. They may serve as a basis of further comparative studies in mice. PMID- 7982079 TI - Mu and delta opioid receptors mediate opposite modulations by morphine of the spinal release of cholecystokinin-like material. AB - The possible modulations by morphine and various opioids of the spinal release of cholecystokinin-like material (CCKLM) evoked by 30 mM K+ was studied in vitro, using slices of the dorsal part of the rat lumbar enlargement superfused with an artificial cerebrospinal fluid. Addition of the mu agonist, DAGO (0.1-10 microM), to the perfusing fluid produced a concentration-dependent decrease in the peptide release, which could be prevented by the preferential mu antagonist, naloxone. Complex modulations were induced by the delta agonist, DTLET, as this drug inhibited CCKLM release when added at 10 nM-3 microM to the perfusing fluid, but enhanced it at 10 microM. Both effects were preventable by the delta antagonists naltrindole and ICI 154129, suggesting that delta receptors, possibly of different subtypes, mediated the inhibition and stimulation by DTLET. Morphine also exerted a biphasic effect, as the alkaloid decreased CCKLM release at 0.01 0.1 microM and enhanced it at 10 microM. Morphine-induced inhibition was preventable by naloxone, whereas its stimulatory effect could be blocked by naltrindole and ICI 154129. Although inactive on its own on CCKLM release, the selective kappa 1 agonist U 50488H (1 microM) prevented the inhibitory effects of both DAGO (10 microM) and morphine (0.1 microM), suggesting the existence of interactions between kappa 1 and mu receptors within the dorsal zone of the rat spinal cord. These data indicate that low concentrations of morphine exert an inhibitory influence on spinal CCKergic neurons that depends on the stimulation of mu opioid receptors. The excitatory influence of 10 microM morphine likely results from the simultaneous stimulation of mu, delta and kappa receptors, as the inhibitory effect of mu receptor stimulation can be masked by that of kappa 1 receptors, allowing only the expression of a delta-dependent excitatory effect similar to that induced by 10 microM DTLET. PMID- 7982080 TI - Muscarinic receptor-dependent activation of phospholipase C in the developing human fetal central nervous system. AB - The coupling of muscarinic-cholinergic receptors (mAChR) to adenylate cyclase and phospholipase C (PLC) second messenger systems has been demonstrated in many animal species. However, little is known about this association in the developing human central nervous system. Because of the proposed role of acetylcholine in the regulation of development and differentiation of neural cells, an understanding of these relationships during human fetal development gains importance. We report, in this communication, the coupling of mAChR with PLC in the human fetal brain. This coupling was determined using two independent approaches that relied upon estimating the accumulation of inositol phosphates (IPs) and cytidine diphosphate diacylglycerol (CDP-DAG). Carbachol treatment of brain slices, in the presence of lithium, resulted in the accumulation of IPs. Analysis of the kinetics of this accumulation showed that IP3 and IP2 increased rapidly, reaching a peak or plateau before IP. The results also showed that agonist-stimulated PLC produced two second messengers, IP3 and DAG. The production of DAG was strongly supported by the carbachol-dependent increase of CDP-DAG. The accumulation of IP and CDP-DAG was dependent on agonist concentration. The obtained EC50 values were approximately: carbachol 47 microM; acetylcholine 6 microM; and oxotremorine 25 microM. Unexpectedly, all three agonists demonstrated a similar efficacy. The cholinergic stimulation of inositide hydrolysis appears to be the result of activation of the m1 muscarinic receptor. PMID- 7982081 TI - Brain lesions and water-maze learning deficits after systemic administration of kainic acid to adult rats. AB - The relationship between hippocampal damage and spatial learning deficiencies was studied in rats injected with kainic acid (10 mg/kg i.p.). A single injection was given either before or after the acquisition phase of the Morris water-maze task. In this acquisition phase, the animals were required to find a hidden underwater platform starting from four different points. The task was repeated twice a day for 10 days. In the retention phase after 10 days rest, the rats repeated the same task. The damage caused by the treatment occurred in several prosencephalic areas, including the piriform and enthorhinal cortices, the thalamus and the hippocampus. In the latter, greatest damage was seen in CA1 followed by CA3 while CA2 and the gyrus dentatus appeared almost unaffected. The behavioural results indicated that kainic acid impaired but did not preclude the acquisition of the water-maze task. During the retention phase, no significant differences in latencies were found between animals that were treated before and after acquisition, thus, indicating that pretraining does not play an important role in the recovery of these spatial abilities following hippocampal lesions. PMID- 7982082 TI - Effects of chronic intraventricular nerve growth factor treatment on vasoactive intestinal peptide and neuropeptide Y levels in the hippocampal formation and cerebral cortex following fimbrial transections. AB - The present study determined whether chronic intracerebroventricular (i.c.v.) nerve growth factor (NGF) treatment alters the hippocampal content of vasoactive intestinal peptide (VIP) or neuropeptide Y (NPY) in rats with unilateral fimbrial transections. In addition, effects of chronic NGF treatment on cortical VIP and NPY levels were determined. Following partial and full fimbrial transections, hippocampal choline acetyltransferase (ChAT) activity was reduced by 41% and 60% ipsilateral to the lesioned side, respectively. Chronic NGF treatment partially attenuated (by 48%) the reduction of ChAT following partial lesions, but not full lesions. Neither the hippocampal contents of VIP or NPY were altered by partial or full fimbrial transections nor by chronic NGF treatment. However, in the NGF treated rats, significant increases not only in cortical ChAT activity (by 28%), but also cortical VIP levels (by 68%) were observed. Cortical NPY levels remained unchanged following chronic NGF administration. In summary, the results suggest that the increases in cortical VIP levels observed in chronic NGF-treated rats may be specific to this tissue and consequent to the enhanced cholinergic tone exerted by this neurotrophin in the basalocortical pathway. Additionally, it appears that NGF when administered in pharmacological doses is not involved in the regulation of NPY synthesis in the hippocampus or cortex despite the presence of an NGF-responsive element associated with the rat NPY gene. PMID- 7982083 TI - Alpha-sialyl cholesterol increases laminin in Schwann cell cultures and attenuates cytostatic drug-induced reduction of laminin. AB - Schwann cells play an important role in peripheral nerve regeneration. Here, we report the effect of alpha-sialyl cholesterol (alpha-SC), a derivative of the sialic acid-containing natural gangliosides, and the cytostatic agents, cisplatin, taxol and vincristine on the laminin production in Schwann cell cultures isolated from rat sciatic nerves. Laminin, one of several extracellular matrix components produced by Schwann cells, is known to potentiate axonal outgrowth. Laminin content was increased by alpha-SC, starting at 7.0 micrograms/ml with a maximal effect at 22.4 micrograms/ml (30%, P < 0.001). The three cytostatic drugs, dose-dependently reduced laminin content in Schwann cell cultures: (1) cisplatin at a threshold dose of 2 micrograms/ml (-26.4%, P < 0.001); (2) taxol, starting at a dose of 1 ng/ml (-8.0%, P < 0.05); and (3) vincristine, starting at 0.5 ng/ml (-5.9%, P < 0.05). Cultured Schwann cells were incubated with cytostatic drugs in combination with increasing amounts of alpha SC and it was found that, depending on the cytostatic drug concentration used, alpha-SC could reduce or completely prevent the cytostatic drug-induced reduction of laminin in Schwann cell cultures. Co-treatment with alpha-SC also reduced part of the morphological changes caused by the cytostatic drugs. alpha-SC did not counteract the anti-proliferative effect of the cytostatic drugs on K-562 human erythroleukemia cells. In conclusion, alpha-SC increased laminin content in Schwann cell cultures and protected Schwann cell cultures against the decrease of laminin by cytostatic drugs without interfering with the anti-proliferative potential, suggesting that alpha-SC may have clinical use in protecting cancer patients against the neurotoxic effects of cytostatic drugs. PMID- 7982084 TI - Dendritic spine density in the lobus parolfactorius of the domestic chick is increased 24 h after one-trial passive avoidance training. AB - One to three day old chicks spontaneously peck at small objects. When presented with a chrome bead coated with the bitter tasting substance methyl anthranilate (MeA), chicks peck once, display a characteristic disgust response and subsequently avoid a similar bead. Chicks that are trained on a water coated bead continue to peck a similar bead on retrial. Twenty four hours after training on this one-trial passive avoidance paradigm, chicks were tested for retention. The brains of chicks displaying the correct behavioural response (> 90%) were removed and the lobus parolfactorius from each hemisphere was dissected from the brain and impregnated using a rapid Golgi technique. Analysis of large multipolar neurones by centrifugal dendritic branch order showed that there were significantly more spines on all orders examined in the left hemispheres of MeA trained chicks compared to water-trained control chicks. Significantly higher spine densities were also found on 4th and 5th order branches of neurones in the right lobus parolfactorius of MeA-trained chicks compared to water-trained chicks. No significant difference in dendritic length was observed. These results suggest that substantial plasticity occurs in post-synaptic structures in the lobus parolfactorius following passive avoidance training. It is suggested that this plasticity is related to processes involved in long term information storage. PMID- 7982085 TI - Selective modulation of the NPY receptors of the Y2 subtype by alpha 2 receptors in the nucleus tractus solitarii of the rat. A cardiovascular and quantitative receptor autoradiographical analysis. AB - The modulation of neuropeptide Y (NPY) receptors by alpha 2 receptors in the nucleus tractus solitarii (Sol) of the rat was evaluated using quantitative receptor autoradiography and measurements of mean arterial blood pressure and heart rate. The receptor autoradiographical experiments showed that clonidine (10 nM), a selective alpha 2 receptor agonist, induced a 59% increase in the B0 value and a 47% decrease in the IC50 value of NPY(1-36) when competing for [125I]peptide YY ([125I]PYY)-binding sites in the presence of [Leu31, Pro34]NPY (100 nM), a selective NPY Y1 receptor agonist, to block the binding to NPY Y1 receptors. In contrast, when NPY(13-36) (300 nM), a selective NPY Y2 receptor agonist, was used to block the binding to NPY Y2 receptors, clonidine (1-30 nM) did not affect the B0 value and the IC50 value of NPY(1-36) when competing for [125I]PYY-binding sites, suggesting that the stimulation of alpha 2 receptors can selectively increase the affinity of NYP(1-36) for the NPY Y2 receptor. Microinjections of threshold doses of adrenaline or clonidine into the Sol not only counteracted the vasopressor action of a close to ED50 dose of coinjected NPY(13-36), but also changed the vasopressor and tachycardic response produced by NPY(13-36) into a vasodepressor and bradycardic response. However, threshold doses of adrenaline or of clonidine microinjected into the Sol did not modify the vasodepressor responses to a close to ED50 dose of NPY(1-36) or of [Leu31, Pro34]NPY.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7982086 TI - CRF receptor antagonist attenuates stress-induced noradrenaline release in the medial prefrontal cortex of rats. AB - Noradrenaline release in rat medial prefrontal cortex (PFC) was measured using a brain microdialysis technique. Immobilization stress increased noradrenaline release to a maximum level of 248.7 +/- 12.8% of the basal release, which was significantly attenuated by preinjection of alpha-helical CRF9-41 (50 micrograms/rat) into the lateral cerebroventricle. Intracerebroventricular injection of CRF also increased noradrenaline release in the medial PFC. These results suggest that immobilization-stress facilitates noradrenaline release in the medial PFC through activation of the CRF system in the brain. PMID- 7982087 TI - Dendritic branching in cortical pyramidal cells in response to ovariectomy in adult female rats: suppression by neonatal exposure to testosterone. AB - Female Long-Evans rats were treated with oil or testosterone propionate (TP) at birth (postnatal day zero, PN0) and PN1. As adults, animals from each group were ovariectomized or sham operated. Four months later the brains were prepared using a modified Golgi-Cox staining procedure. In neonatally oil-treated females, ovariectomy in adulthood increased the dendritic arbor of layer II/III pyramidal neurons of the parietal cortex; in addition, there were modest increases in apical dendritic spine density. The dendritic arbor of the pyramidal neurons of intact neonatally TP-treated females was greater than that of intact oil-treated females, but in these animals there was no increase in dendritic arbor in response to ovariectomy. PMID- 7982088 TI - Characterization of cytokine-induced hyperalgesia. AB - Agents which induce symptoms of illness, such as lipopolysaccharide (LPS), cause diverse effects including hyperalgesia. While previous studies have examined central pathways mediating LPS hyperalgesia, the initial steps in activating this system remain unknown. Since LPS induces the release of various cytokines and eicosinoids from immune cells, the present series of experiments examined the potential involvement of these substances in LPS hyperalgesia. This work demonstrates that: (a) Interleukin-1 beta (IL-1 beta) can produce hyperalgesia following either intraperitoneal or intracerebroventricular injection. In contrast, IL-1 beta delivered intrathecally did not affect pain responsivity. (b) Liver macrophages (Kupffer cells) appear to be critically involved, and relay signals to the brain via hepatic vagal afferents. (c) Both IL-1 beta and tumor necrosis factor appear to be critical mediators of LPS hyperalgesia. In contrast, prostaglandins do not appear to be involved. Taken together, these studies suggest that substances classically thought of as products of the immune system may dynamically enhance pain responsivity via actions either on the hepatic vagus or at central sites. PMID- 7982089 TI - Pulse repetition rate increases the minimum threshold and latency of auditory neurons. AB - The effect of pulse repetition rate on auditory sensitivity of the big brown bat, Eptesicus fuscus, was studied by determining the minimum threshold, response latency and recovery cycle of inferior collicular neurons at different repetition rates under free field stimulation conditions. In general, collicular neurons shortened the response latency and increased the number of impulses monotonically or non-monotonically with stimulus intensity. They recovered at least 50% when the interpulse interval was 10-57 ms. In addition, they increased the minimum threshold, lengthened the response latency, and reduced the number of impulses discharged to each pulse with increasing repetition rate. The increase in minimum threshold with repetition rate is partly because the neuron can not recover from previous stimulation when the interpulse interval is shortened. This increase reduces a neuron's response sensitivity and thus diminishes its number of impulses to each presented pulse. This increase also reduces the effectiveness of a given stimulus intensity which contributes to the lengthening of the neuron's response latency. Data obtained from single neuron recordings are used to highlight these observations. Implications of present findings regarding the bat's echolocation are also discussed. PMID- 7982090 TI - The BE (2)-M17 neuroblastoma cell line synthesizes and secretes corticotropin releasing factor. AB - The BE (2)-M17 human neuroblastoma has previously been shown to express corticotropin-releasing factor (CRF) mRNA following retinoic acid treatment. It is demonstrated in this report that both cell extracts and cell incubation medium of retinoic acid-treated BE (2)-M17 cells were shown to contain CRF-like immunoreactivity (CRF-LI) by RIA. CRF-LI secretion and content were also dose dependently increased by forskolin. In addition, cell extracts were applied to a C18 Vydac column and peak CRF-LI from the collected fractions was shown to coincide in time of elution with peak immunoreactivity seen with oxidized synthetic CRF standard. Thus, in containing the CRF peptide, the BE (2)-M17 cells are useful models for further study of CRF cellular and genetic regulation. PMID- 7982091 TI - Nitric oxide controls feeding behavior in the chicken. AB - To investigate the effect of nitric oxide (NO) on food intake in the chicken, L NG-nitro-arginine methyl ester HCl (L-NNA), an inhibitor of NO synthase, was applied. When i.p. administered, L-NNA significantly inhibited the food intake of broiler chickens in a dose response manner. Food ingestion was also depressed by the i.c.v. injection of L-NNA in a dose response fashion. The effect of L-NNA was attenuated by i.c.v. administration of L-arginine. These results suggest that central NO may control feeding behavior in the chicken. PMID- 7982092 TI - Changes in blood glucose concentration in the carotid body-sinus modify brain glucose retention. AB - To test whether blood glucose concentration in the carotid body-sinus may influence the amount of glucose retained by the brain, the isolated carotid sinus was perfused with glucose-rich blood or glucose-poor blood from a second animal. The circulation of the right carotid body-sinus was temporarily isolated in rat A, and perfused with blood coming from rat B. Blood glucose in rat B was modified by injections of glucose or insulin. Changes in glucose retention by the brain were measured in rat A. When the isolated carotid body-sinus in rat A was perfused with hyperglycemic blood (16.7 mM), brain glucose retention in rat A decreased significantly from 0.14 +/- 0.02 mumol/g/min (t = 0) to 0.08 +/- 0.01 mumol/g/min at 4 min after the beginning of perfusion. In contrast, the perfusion of the isolated carotid body-sinus of rat A with hypoglycemic blood (2.7 mM) from rat B, had the opposite effect. Brain glucose retention in rat A increased (0.23 +/- 0.03 mumol/g/min) at t = 4 min in comparison to control values (0.13 +/- 0.01 mumol/g/min). Chemoreceptor activity was also manipulated by the injection of cyanide (NaCN) in rat B, under these conditions, brain glucose retention in rat A increased from 0.13 +/- 0.01 mumol/g/min to 0.28 +/- 0.03 mumol/g/min between 4 to 8 min after the beginning of perfusion. These results indicate that chemosensory activity within the carotid body-sinus, superfused in vivo with different glucose concentrations, modify glucose retention by the brain. PMID- 7982093 TI - Nordihydroguaiaretic acid protects hippocampal neurons against amyloid beta peptide toxicity, and attenuates free radical and calcium accumulation. AB - Recent findings indicate that amyloid beta-peptide (A beta) can be neurotoxic by a mechanism involving an increase in the concentration of intracellular free Ca2+ ([Ca2+]i) and the generation of free radicals. In the present study, the lipoxygenase inhibitor/antioxidant nordihydroguaiaretic acid (NDGA) protected cultured rat hippocampal neurons against the toxicity of A beta in a concentration-dependent manner. Measurements of cellular oxidation (using the oxidation-sensitive dye 2,7-dichlorofluorescin) and intracellular free Ca2+ levels (using the Ca2+ indicator dye fura-2), showed that NDGA suppressed A beta induced accumulation of reactive oxygen species (ROS) and Ca2+; Ca2+ responses to glutamate were also suppressed by NDGA. NDGA prevented neuronal injury and accumulation of ROS induced by iron, indicating a role for NDGA as an antioxidant in NDGA-mediated neuroprotection. Another lipoxygenase inhibitor (AA861) also protected against A beta and iron toxicity whereas the the 5-lipoxygenase activating protein inhibitor L655,238 and the cyclooxygenase inhibitor indomethacin were ineffective. These findings suggest that NDGA can interupt a neurodegenerative pathway relevant to the pathophysiology of Alzheimer's disease. PMID- 7982095 TI - Increased synthesis of specific proteins during glutamate-induced neuronal death in cerebellar culture. AB - We have previously shown that glutamate-induced neurotoxicity is mediated by a sodium-chloride component and a calcium component in our cerebellar granule cell culture. In order to further characterize these two different components, the time course of neuronal death induced by glutamate (100 microM) in basal solution and in low sodium-chloride solution was studied by morphological and biochemical criteria. As shown by phase-contrast microscopy, cerebellar granule cells exhibited clear neuronal degeneration within 4 h after exposure to this excitotoxin. These morphological changes correlated [35S]methionine incorporation into proteins which rapidly declined during the first hour of treatment. Qualitative change in [35S]methionine incorporation into proteins was further investigated by two-dimensional gel electrophoresis performed after glutamate exposure in basal solution and in low sodium-chloride solution. Most of the proteins showed a decreased labelling after glutamate exposure as expected, but some polypeptides showed an increased labelling or appeared to be newly synthesized. Furthermore, a different pattern of protein synthesis was observed when glutamate exposure was performed in basal solution or in low sodium-chloride solution. The identification of these polypeptides and their implication in the neuronal death are discussed. PMID- 7982094 TI - Quantal properties of H-type glutamatergic synaptic input to the striatal medium spiny neurons. AB - The striatal medium spiny neuron receives two distinct glutamatergic synaptic inputs, S-type and H-type inputs, which have very different amplitudes. We report here that peak amplitudes of unitary H-type excitatory postsynaptic currents (EPSCs) could be reduced by decreasing external Ca2+, unlike S-type EPSCs. This suggests that H-type EPSCs are multiquantal, and supports the idea that the cellular origin of H-type EPSCs is distinct from that of the S-type EPSCs. PMID- 7982096 TI - Action of angiotensin converting enzyme inhibitors in rat brain: interaction with isoproterenol assessed by Fos immunocytochemistry. AB - Low and high doses of angiotensin converting enzyme (ACE) inhibitors have been shown either to enhance or suppress, respectively, the water intake of rats induced by acute administration of isoproterenol. In order to assess the role and sites of action of angiotensin II (Ang II) in this dual action of ACE inhibitors, rats were administered either low or high doses of enalapril or captopril, followed by isoproterenol, and were sacrificed 1 h later for determination of Fos like immunoreactivity (FLI) in brain. Isoproterenol induced strong FLI in the magnocellular paraventricular (PVN) and supraoptic (SON) nuclei, and moderate staining along the structures of the rostral wall of the lamina terminalis (LT). Low doses of ACE inhibitors either had no effect or slightly increased FLI along the LT following isoproterenol. Enalapril reduced FLI in some other regions, including the parvocellular PVN. In contrast, high doses of ACE inhibitors abolished FLI along the LT, and reduced FLI in the PVN and SON. Captopril, but not enalapril, induced some FLI in the LT, SON and PVN. The data are discussed in terms of access of ACE inhibitors to the brain, and interactions with structures involved in Ang-related water intake. PMID- 7982097 TI - Intracellular response of neurons of the caudate nucleus and putamen to intrastriatal stimulation in cat. AB - The purpose of this research was to determine if the different functional areas of the striatum, as defined by corticostriate connections, have excitatory and/or inhibitory interconnections. In cats anesthetized with barbiturates, an intracellular recording electrode was angled at 45 degrees such that it (1) crossed all functional areas of the striatum in a single pass and (2) traversed perpendicular to intrastriatal axonal bundles and their terminal fields. > 95% of the neurons recorded intracellularly in the head of the caudate (Cd) nucleus responded to stimulation of the rostromedial striatum (limbic area) producing an initial excitatory response in all cases. Membrane hyperpolarization and inhibition followed the initial excitatory response in approximately half of the responsive neurons. As the recording electrode approached the stimulating electrode, latencies to response onset decreased and amplitudes of the initial excitatory responses increased. Stimulation of a single site produced responses in neurons found in all functional areas of the Cd nucleus. Based on the known topography of afferents to the striatum, these results cannot be explained by stimulation of fibers en passant. Therefore, we conclude that the limbic striatum is connected to other functional areas of the Cd nucleus by intrinsic excitatory and inhibitory circuits. We speculate that intrinsic circuits are a hidden layer of organization providing connectional plasticity by which the influence of an input on striatal neurons may be expanded or contracted beyond the anatomical limits of the afferent terminal field. PMID- 7982098 TI - Regional extracellular norepinephrine responses to amphetamine and cocaine and effects of clonidine pretreatment. AB - Microdialysis in behaving animals was used to characterize the hippocampus (HP) and prefrontal cortex (PFC) norepinephrine (NE) responses to amphetamine (AMPH) and cocaine (COC). NE exhibited regionally similar dose- and time-dependent increases to each drug. However, peak NE concentrations were approximately 2-fold greater at behaviorally similar doses of AMPH compared with COC. To examine the role of noradrenergic impulse flow in the mechanism(s) by which these stimulants enhance extracellular NE, groups of animals were pretreated with the alpha 2 autoreceptor agonist, clonidine (CLON), prior to stimulant administration. CLON (50 micrograms/kg) administration completely blocked the NE response to both 20 and 30 mg/kg COC. By contrast, CLON decreased the NE response to 0.5 mg/kg AMPH by 75%, but became progressively less effective on the response as the dose was increased to 1.75 and 5.0 mg/kg. CLON also had no effect on the caudate dopamine responses to either AMPH or COC, consistent with the presumed specificity of this drug for alpha 2 receptors and suggesting the absence of any significant pharmacokinetic interactions. These results indicate that COC acts an uptake blocker at NE-containing neurons and suggest that AMPH increases extracellular NE through two consequences of its interaction with the neuronal transport carrier: (1) reuptake blockade which predominates at lower doses; and (2) release which becomes more prevalent at higher doses. Behavioral analyses revealed effects of CLON which varied as a function of stimulant and dose. PMID- 7982100 TI - Postnatal development of argyrophilic nucleolar organizer regions in the mammillary body of undernourished rats. AB - The effects of undernutrition during pregnancy and/or lactation periods on cortical structures have already been reported. However, its effect on non cortical areas like the hypothalamic, that participates in the regulation of the autonomic nervous system or food intake, has not been extensively investigated. We studied the postnatal development of the medial mammillary nucleus (hypothalamus) in the rat offspring that had a dietary restriction in utero and during lactation. The argyrophilic nucleolar regions (Ag-NORs), that represent the transcriptional activity of the cell, were quantified in their neurons. No statistically significant differences were found in the results between the control and undernourished groups in the ages studied (7, 14, 21 and 30 days). However, a delay in the neuronal activity of the latter group was observed. A critical period in the development of this nucleus, at about 21 days of age, was also seen in both groups. After this age, the activity levels remained steady. PMID- 7982099 TI - Unilateral optic nerve transection decreases 2-[125I]-iodomelatonin binding in retinorecipient areas and visual pathways of chick brain. AB - In chick brain, specific 2-[125I]-iodomelatonin-binding was localized primarily in the visual system, i.e., retinorecipient and relay nuclei and fiber tracts of the tectofugal, thalamofugal, circadian and accessory visual pathways. Unilateral transection of the optic nerve (ONX) significantly reduced the binding of 2 [125I]-iodomelatonin (75 pM) in many, but not all, primary retinal targets and visual pathways at 7 and 14 days, but not 1 day, postlesion. As measured using quantitative autoradiography, 2-[125I]-iodomelatonin binding was decreased by 90% in both the central portion of the lesioned optic tract and one of its targets, the nucleus of the basal optic root (nBOR). Other retinorecipient areas exhibiting substantial decreases (60%) in 2-[125I]-iodomelatonin-binding included the optic tectum, lateroventral and dorsolateral geniculate nuclei and tectal gray area contralateral to the lesion. These findings are consistent with the hypothesis that melatonin receptors are located presynaptically on incoming optic nerve terminals in many retinorecipient areas. This localization may account for most of the binding sites in nBOR. In other primary visual areas, however, melatonin receptors also appear to be located on postsynaptic cells and/or non retinal afferents. ONX had no significant effect on 2-[125I] -iodomelatonin binding in two retinorecipient areas, the visual suprachiasmatic nucleus and the dorsolateral anterior thalamus, which are part of the circadian/oculomotor and thalamofugal pathways, respectively. An unexpected consequence of ONX was that 2 [125I]- iodomelatonin binding was decreased in certain secondary (nucleus rotundus, isthmi nuclei) and tertiary level (ectostriatum) nuclei along the prominent tectofugal visual pathway. Binding in the tectorecipient nucleus triangularis was not significantly altered, however. Analysis of secondary level relay nuclei in the oculomotor pathway revealed that binding after ONX was decreased in the ipsilateral Edinger-Westphal nucleus but not in the oculomotor nuclei. Selective transsynaptic changes in 2-[125I]-iodomelatonin binding after lesion of the visual input most likely reflect activity-dependent regulation and functional plasticity of central melatonin receptors. PMID- 7982101 TI - Glucocorticoids increase extracellular [3H]D-aspartate overflow in hippocampal cultures during cyanide-induced ischemia. AB - Glucocorticoids (GCs), the adrenal steroid hormones secreted during stress, exacerbate neuronal death in the hippocampus during ischemia. Since ischemia brain damage is ascribed to an elevated level of extracellular excitatory amino acids (EAAs), this study was undertaken to investigate the effect of GCs on EAA homeostasis in hippocampal cell cultures during the insult of cyanide exposure. Using D-[2,3-3H]aspartic acid ([3H]D-Asp) as a tracer, we found that corticosterone (CORT, the physiological GC in rats) increased the accumulation of extracellular [3H]D-Asp by 25% in hippocampal cultures during cyanide-induced ischemia. CORT had no effect on the release of [3H]D-Asp. Instead, analysis of [3H]D-Asp uptake kinetics indicates that CORT decreased the maximum uptake rate and the Michaelis constant by 44% and 50%, respectively, in cells treated with cyanide. It is concluded that, during cyanide-induced ischemia, CORT might enhance extracellular overflow of [3H]D-Asp by decreasing its uptake, thereby endangering neurons. PMID- 7982102 TI - Injections of excitatory amino acid antagonists into the median raphe nucleus produce hippocampal theta rhythm in the urethane-anesthetized rat. AB - The median raphe nucleus (MR) exerts a pronounced desynchronizing influence on the hippocampal EEG. MR stimulation disrupts theta, while MR lesions produce constant uninterrupted theta. The MR receives pronounced excitatory amino acid (EAA)-containing afferents that have been implicated in several MR-mediated behaviors. The present study examined the effects on the hippocampal EEG of MR injections of the following EAA antagonists in the urethane-anesthetized rat: 2 amino-7-phosphonoheptanoate (AP-7), dizocilpine maleate (MK-801), and gamma glutamyl-aminomethylsulfonic acid (GAMS). MR injections of the competitive (AP-7) and non-competitive (MK-801) N-methyl-D-aspartic acid (NMDA) receptor antagonists produced theta at short latencies (2.86 min; 4.02 min, respectively) and for long durations (116.1 min; 66.8 min, respectively). It was further shown that the theta-eliciting effects of AP-7 injections could be reliably and temporarily reversed with MR injections of NMDA. MR injections of the kainate/quisqualate receptor antagonist (GAMS) also produced theta at relatively short latencies (6.5 min) and for long durations (60.5 min) indicating that EAA effects on the MR are not NMDA receptor specific. Injections of each of the foregoing EAA antagonists into regions of the brainstem adjacent to the MR including the dorsal raphe nucleus and the medullary or pontine reticular formation generated theta at very long latencies or were without effect. The present findings indicate EAA afferents to the MR normally exert an excitatory influence on the MR in its desynchronization of the hippocampal EEG, whereas the removal of EAA inputs to MR produces the opposite: a reduction of MR activity and hence the elicitation of theta.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7982103 TI - Radiology research: from 1970 through 1990 and toward 2000. PMID- 7982104 TI - Imaging of soft-tissue sarcomas. AB - Soft-tissue sarcomas are encountered only infrequently, but their diagnosis is important because the long-term prognosis is usually good if the tumour is properly managed. The role of various imaging modalities in the evaluation of these neoplasms is discussed, with special emphasis on magnetic resonance imaging. The authors review the importance of imaging in tumour detection, characterization, staging and surveillance after therapy, and they emphasize the critical subject of proper biopsy technique. PMID- 7982105 TI - Transcranial Doppler ultrasonographic changes after embolization of cerebral arteriovenous malformations. AB - The authors assessed the potential role of transcranial Doppler ultrasonography (US) in monitoring hemodynamic changes induced by embolization of cerebral arteriovenous malformations. Transcranial Doppler US was performed in eight patients with such lesions before and after embolization with n-butyl cyanoacrylate [corrected]. Changes in mean flow velocity and pulsatility index were analysed in all feeding and nonfeeding arteries. Anatomic and hemodynamic observations were also correlated with the results of digital subtraction angiography. A consistent trend was observed in all treated feeding arteries after embolization: the flow velocity decreased by a mean of 26% or 33 cm/s (p = 0.01, paired t-test), and the pulsatility index increased by a mean of 27% or 0.15 (p = 0.005). Although these changes did not correlate with the degree of angiographic reduction of the nidus (r = -0.31), they were most marked in malformations with a lower Spetzler grade or a higher degree of shunt obliteration. After embolization, recruitment of untreated feeding arteries was documented in two cases and a decrease in the "steal effect" from contralateral nonfeeding arteries in three. Changes in the nonfeeding arteries ipsilateral and contralateral to the malformation were variable. The authors conclude that transcranial Doppler US is a convenient and reliable method to evaluate quantitatively the hemodynamic effects of embolization of cerebral arteriovenous malformations. PMID- 7982106 TI - Effect of hyoscine butylbromide on gastroesophageal reflux in barium studies of the upper gastrointestinal tract. AB - Hyoscine butylbromide (Buscopan) is an intravenously administered hypotonic agent that significantly reduces pressure in the lower esophageal sphincter and may therefore artificially induce gastroesophageal reflux during barium examination of the upper gastrointestinal tract. This study was performed to test this hypothesis. The presence or absence and severity of gastroesophageal reflux before and after intravenous injection of 20 mg Buscopan were evaluated in 112 consecutive patients undergoing biphasic upper gastrointestinal examination. Gastroesophageal reflux was seen in 49 (44%) of the patients. Reflux was evident both before and after the injection of Buscopan in 35 (31%) of the patients, before injection only in 10 (9%) and after injection only in 4 (4%). The magnitude of reflux after injection of Buscopan was reduced or the same in 108 of the patients (96%) and increased in 4 (4%). There was no significant difference in the overall occurrence (p = 0.41) or degree (p = 0.81) of gastroesophageal reflux before and after injection of Buscopan (chi 2 test). The authors conclude that the routine use of Buscopan is unlikely to spuriously increase the frequency or degree of gastroesophageal reflux observed on upper gastrointestinal barium studies. PMID- 7982107 TI - Radiologically guided percutaneous cholecystostomy for acute cholecystitis: long term outcome in 50 patients. AB - To assess the long-term outcome in patients with acute cholecystitis treated initially by percutaneous cholecystostomy, the authors reviewed the medical and radiology records of all such patients treated at their hospital from January 1990 to September 1993. Of the 50 patients, 29 had calculous and 21 had acalculous cholecystitis. In the group with calculous cholecystitis, 1 of the patients required no further treatment, 3 subsequently underwent percutaneous stone removal, 14 underwent elective cholecystectomy, 6 underwent emergency cholecystectomy and 5 died of the underlying condition shortly after cholecystostomy. In the group with acalculous cholecystitis, 12 of the patients needed no further treatment after a mean follow-up period of 12 months; 8 of these underwent follow-up ultrasound examination, which revealed gallbladder calculi in only 1 patient. Four patients underwent elective cholecystectomy, 1 underwent emergency cholecystectomy, and 4 died of the underlying condition shortly after cholecystostomy. Over the long term, 23 (79%) of the 29 patients with calculous cholecystitis underwent surgery or removal of calculi. In the other group surgery was required in only 5 (24%) of the 21 patients. The authors conclude that percutaneous cholecystostomy is a useful temporizing measure, which allows patients with calculous cholecystitis to undergo elective cholecystectomy. In most cases of acalculous cholecystitis the procedure is curative, obviating the need for cholecystectomy. PMID- 7982108 TI - Meningeal myelomatosis. AB - Many neoplasms disseminate along the pathway of the cerebrospinal fluid. Imaging in this setting is usually insensitive, but when there are findings, they have a characteristic appearance. The authors describe a 52-year-old woman with meningeal dissemination of myelomatosis and the classic myelographic appearance of leptomeningeal disease. PMID- 7982109 TI - Magnetic resonance imaging in drug-induced meningitis. AB - Pathologic meningeal enhancement has been reported in patients with bacterial and viral meningitis. The authors describe a 52-year-old woman with drug-induced aseptic meningitis in whom diffuse meningeal enhancement was observed with magnetic resonance imaging after administration of gadolinium diethylenediaminepenta-acetic acid. The cause and mechanism of drug-induced aseptic meningitis and the value of magnetic resonance imaging in the diagnosis of this uncommon condition are stressed. PMID- 7982110 TI - Magnetic resonance features in carbon monoxide poisoning. AB - The authors describe unusual magnetic resonance findings due to carbon monoxide poisoning in a 34-year-old woman. With T2-weighted imaging, increased signal intensity was observed bilaterally in the putamen and the caudate nucleus. Lesions of high signal intensity in the globus pallidus, which have been previously reported, were also observed. PMID- 7982111 TI - Tumour of a peripheral nerve sheath with invasion of the lumbar spine. AB - Tumours of peripheral nerve sheaths are rarely malignant, and even when malignant they are only infrequently associated with extensive destruction of bone. The authors report the computed tomography and magnetic resonance imaging findings for an unusually large sheath tumour that presented with extensive destruction in the lumbar spine. PMID- 7982112 TI - Cytomegalovirus cholangitis after renal transplantation. AB - Clinically significant cytomegalovirus cholangitis is well recognized in patients with AIDS but is less common in other groups of immunocompromised patients. The authors describe a 59-year-old man who had undergone renal transplantation in whom this condition developed, and they emphasize that this diagnosis should be considered in renal transplant patients presenting with biliary obstruction. Careful examination of biopsy material for cytomegalovirus inclusion bodies is necessary. PMID- 7982113 TI - Colonic bull's-eye lesions in histiocytosis X. AB - A 27-year-old woman with known pulmonary, cutaneous and osseous histiocytosis X presented with vague abdominal pain. Double-contrast barium enema examination revealed multiple colonic bull's-eye lesions. Biopsy showed histiocytic infiltration similar to that already described at other sites in this patient (the lungs and bone). To the authors' knowledge, this case represents the first radiologic description of this manifestation of histiocytosis X. Though rare, it should be considered in the differential diagnosis of colonic bull's-eye lesions. PMID- 7982114 TI - Drug-induced diaphragmlike small-bowel strictures. PMID- 7982115 TI - Residents' corner. Answer to case of the month #28. Empyema necessitatis secondary to pulmonary actinomycosis. PMID- 7982116 TI - MRI diagnosis of a ruptured breast implant. PMID- 7982117 TI - Echogenic blood during slow flow. PMID- 7982118 TI - The cardinal importance of sputum microscopy. PMID- 7982119 TI - The respiratory epithelium and airway smooth muscle homeostasis: its relevance to asthma. PMID- 7982120 TI - The therapeutic index of newer H1-receptor antagonists. PMID- 7982121 TI - Effects of ipratropium bromide on bradykinin nasal provocation in chronic allergic rhinitis. AB - Bradykinin (BK) induces albumin exudation and glandular secretion in chronic allergic rhinitis subjects. Since bradykinin may stimulate nociceptive sensory nerves, neural reflex arcs could contribute to the secretion process. Six chronic allergic rhinitis subjects received 1000 nM bradykinin by unilateral nasal provocation using the method of Raphael et al. This dose induces optimal contralateral glandular secretion. Ipratropium bromide (80 micrograms) or saline were applied topically before the challenges. Total protein, albumin, glycoconjugate, and lysozyme were measured in lavage fluids. On the ipsilateral side, bradykinin induced significant total protein, glycoconjugate, and albumin secretion. None of these were affected by ipratropium. On the contralateral side, total protein and glycoconjugates were increased by bradykinin, while albumin and lysozyme were not significantly affected. Ipratropium bromide completely ablated total protein and glycoconjugate secretion on the contralateral side indicating that cholinergic reflexes mediated the glandular secretion. In chronic allergic rhinitis, bradykinin directly stimulated albumin secretion, but also stimulates nociceptive neuron--parasympathetic nerve reflexes to induce glandular secretion. The reflex loop was apparent on the contralateral side to the unilateral bradykinin challenge. This loop induced mucoglycoconjugate, but not serous cell, secretion in chronic allergic rhinitis subjects and can be inhibited by iptratropium bromide. PMID- 7982123 TI - Immune reactivity to Der p I and Der p II in house dust mite sensitive patients attending paediatric and adult allergy clinics. AB - A comparison was made of immune responses to house dust mite allergens in symptomatic patients from paediatric and adult allergy clinics. IgE-specific immune reactivity to Dermatophagoides pteronyssinus was examined by Western blotting and, for Der p I and Der p II, by radioimmune dot-blot using purified allergens. Nineteen mite-sensitive children (mean age 9 years) and 26 adults (mean age 31 years) were compared. Positive IgE responses by dot-blot were found to Der p I and Der p II in 79% of children, whereas reactivity was only present in 23% and 19% respectively of adults, and densitometry indicated a weaker response. In children, Western blotting indicated that the majority of the serologic reactivity was directed to Der p II (17/19, 89%) or a 100 kDa fraction whereas in adults, reactivities were generally directed to other fractions with only 15/26 (58%) recognizing Der p II. Consistent with results of others, a fraction corresponding to Der p I was poorly detected on Western analysis despite positive dot-blots. To determine whether the relative lack of IgE serological immune reactivity in adults was associated with a similar lack of cellular recognition, T-cell proliferation studies were performed, also using purified allergens. Interestingly, these revealed that cellular responsiveness, without serological reactivity, was present in 29% of subjects to Der p I and 50% to Der p II. Proliferative responses were evident in all individuals with specific IgE. PMID- 7982122 TI - Eosinophil cationic protein (ECP), histamine and tryptase in peripheral blood before and during inhalation challenge with toluene diisocyanate (TDI) in sensitized subjects. AB - To determine whether the measurement of specific markers of inflammatory cells in peripheral blood might be used to detect the inflammatory activity in the airways in asthma induced by toluene diisocyanate (TDI), we measured the levels of eosinophil cationic protein (ECP), histamine and tryptase in peripheral blood before and during inhalation challenge with TDI or methacholine in two groups of subjects who exhibited or did not exhibit an asthmatic reaction after exposure to toluene diisocyanate in the laboratory. When the subjects developed a late asthmatic reaction after exposure to TDI, they showed an increase in their ECP serum levels. By contrast, there were no significant changes in serum ECP levels after exposure to TDI in the control group or after methacholine challenge in either group. Tryptase levels in serum were not detectable before or during inhalation challenge with TDI or methacholine. There was no significant increase in plasma histamine levels during inhalation challenge with TDI or methacholine. These results suggest that eosinophils are 'activated' in subjects who develop a late asthmatic reaction after exposure to TDI and that the measurement of ECP levels in peripheral blood may be a useful marker to monitor airway inflammation. PMID- 7982124 TI - Allergenic characterization of Acarus siro and Tyrophagus putrescentiae and their crossreactivity with Lepidoglyphus destructor and Dermatophagoides pteronyssinus. AB - Allergenic components in extracts of Acarus siro and Tyrophagus putrescentiae were identified by sodium dodecyl sulphate-polyacrylamide (SDS-PAGE) and immunoblotting. Five and four allergenic components, respectively, were visualized with sera from farmers sensitized to storage mites. The highest frequency of IgE-binding was to a 15 kDa component of A. siro (7/9 sera) and a 16 kDa component of T. putrescentiae (23/29 sera). The allergenic crossreactivity of A. siro and T. putrescentiae with Lepidoglyphus destructor and Dermatophagoides pteronyssinus was studied with an immunoblotting inhibition technique. Crossreactivity between D. pteronyssinus on the one hand and A. siro and T. putrescentiae on the other, was shown, as the IgE reactivity to a 25 kDa component of D. pteronyssinus was inhibited to the same degree by extracts of A. siro, T. putrescentiae and D. pteronyssinus. However, D. pteronyssinus was a poor inhibitor of the allergenic components of A. siro and T. putrescentiae. Strong cross-reactivity was also shown between L. destructor and the allergenic components of A. siro and T. putrescentiae, while the latter mite species only to a very low degree inhibited the allergenic components of L. destructor. PMID- 7982125 TI - A two-site monoclonal antibody ELISA for the quantification of group V allergens in grass extracts. AB - A two-site solid-phase enzymimmunoassay was used for the quantification of group V allergen in grass pollen extracts in mass units. The assay is based on the monoclonal antibodies (MoAbs), 1D11 and 3B2 which recognize different epitopes on the standard Phl p V. The MoAb-ELISA is very sensitive (15-100 ng/ml Phl p V) and highly specific for group V allergens. Six pollen extracts of different grasses demonstrated parallel binding curves. The group V content ranged between 73 and 673 micrograms/ml in the extracts. The International Standard of Phleum pratense (IS 82/520) contains 400 micrograms/ml Phl p V. A good correlation was observed between the group V content and RAST inhibition, with the exception of Poa pratensis. PMID- 7982126 TI - cDNA sequence analysis of the main olive allergen, Ole e I. AB - Olea europaea (Ole e) I-specific cDNA sequences were amplified by 3'-RACE-PCR, using specific primers based on the N-terminal sequence of the allergen, and cloned into appropriate vectors. The nucleotide sequence data obtained revealed the presence of isogenic variation in Ole e I gene(s). The molecular mass, pI, amino acid composition and sequence of the predicted polypeptides agree with data previously obtained by analysis of purified Ole e I from pollen. Furthermore, by treatment of purified Ole e I with specific glycopeptide hydrolases it has been demonstrated the presence of N-glycosylation in the allergen, and there is a unique concensus site for N-linked glycosylation at positions 111-113 of the deduced amino acid sequence. The Ole e I predicted sequence shows a significant homology with three putative proteins encoded respectively by the another specific LAT52 gene from tomato and the pollen specific genes Zmc13 from maize and OSPSG from rice, suggesting that these proteins could have a role in one of the development processes unique to male gametophytes. PMID- 7982127 TI - High anti-IgE levels at birth are associated with a reduced allergy prevalence in infants at risk: a prospective study. AB - Development of atopic disease was prospectively studied in 148 children from birth to the age of 18 months and related to serum levels of IgG anti-IgE antibody. Children with a dual heredity of allergy, but remaining healthy, had significantly higher IgG anti-IgE levels at birth than children with a similar predisposition to allergy, who became allergic. Children with increased allergy risk, defined by elevated IgE levels at birth (> = 0.53 kU/l) and with probable allergy symptoms had also significantly higher IgG anti-IgE levels at birth than children of the same risk group, developing definite allergy. Independent of allergy risk, there was a significantly lower prevalence of atopic disease in children with cord serum levels of IgG anti-IgE above 350 AU/l than in children with lower levels. Additionally, we showed that the allergy predictive capacity of IgE levels in cord serum was slightly improved in specificity, sensitivity and efficiency by including not only the family history of allergy, but also cord serum levels of IgG anti-IgE. Our results thus raise the possibility that high levels of IgG anti-IgE protect children of increased allergy risk from early development of atopic disease and reduce the severity of symptoms. PMID- 7982128 TI - The evaluation of a cell dispersion method of sputum examination. AB - In recent studies, sputum smear cell counts were found to be reproducible and usefully applied to research in asthma and other airway conditions. However, cell definition on the smears is poor, and the procedure is tedious and has limited utility. The objective of this study is to improve the methods of sputum examination. The subjects used in this study were people with bronchitis or asthma from whom sputum could be obtained. By inverted microscopy, portions of fresh sputum were selected to exclude salivary contamination. These portions were exposed to different volumes of dithiothreitol for varied time intervals. We used the resulting cell suspensions to perform total cell counts and prepare cytospins for differential cell counts and immunohistochemical stains for GM-CSF, EG2, TNF alpha and IL-8. Cytospins were compared with smears for differential cell counts on the same sputum specimens. Excellent cell dispersion and definition in cytospins could be observed. The time required for differential cell counting on cytospins was reduced and cytospin counts were more reproducible than smears. Greater duration of treatment of sputum with dithiothreitol tended to increase total cell counts and significantly decreased EG2 staining but had no effect on differential cell counts or the cytokine cell components. Therefore the proposed method of sputum examination involving cell dispersion and use of cytospins overcomes a number of the disadvantages of the examination of smears. PMID- 7982129 TI - Effect of inhaled atrial natriuretic peptide on methacholine induced bronchoconstriction in asthma. AB - We have previously demonstrated that intravenous and inhaled atrial natriuretic peptide (ANP) significantly inhibits histamine induced bronchoconstriction in asthmatic patients. The current study was designed to determine whether inhaled ANP was also able to inhibit the effects of methacholine. Eight atopic asthmatic patients (five women) were studied: mean (SD) age 38.2 (8.3) years flow expiratory volume per second (FEV1) 2.97 (0.60) litres, equivalent to 92 (13) % of the predicted. Each had demonstrated at least mild bronchial hyperreactivity to inhaled methacholine at screening (geometric mean PC20 1.02 mg/ml; range 0.11 6.54 mg/ml). Patients attended for 3 study days and after baseline spirometry received 3.5 ml saline (placebo), 0.1 mg ANP or 1 mg ANP (ANP dissolved in 3.5 ml saline) in a randomized, double-blind manner via a Mizer aerosol conservation device. Aerosolization took approximately 9 min and FEV1 was repeated at 0.5, 1.5 and 3 min after completion. Immediately thereafter each patient received a 2 min inhalation of methacholine at a dose individually calculated to give a 25% fall in FEV1 (as extrapolated at their initial screening visit) and the FEV1 was followed over the next 20 min. Mean (SEM)% FEV1 did not change significantly after ANP being -4.3 (1.7), -3.2 (2.7) and -2.4 (1.2) after placebo, 0.1 mg ANP and 1 mg ANP respectively. The mean (SEM) maximum fall in FEV1 after methacholine was as follows: placebo 26.9 (5.7)%, 0.1 mg ANP 18.2 (4.3)% and 1.0 mg 11.2 (2.7)% (P < 0.05 placebo vs 1 mg ANP). These results demonstrate that ANP offers significant protection against methacholine induced bronchoconstriction in asthmatic patients. PMID- 7982130 TI - Guided tissue regeneration in surgically created 3-walled and 2-walled periodontal osseous defects in monkeys. AB - BACKGROUND: In the previous clinical studies, guided tissue regeneration resulted in periodontal regeneration after treatment of 3-walled intrabony defects. The purpose of the present study was to compare the regenerative potential of 3 walled and 2-walled surgically created periodontal osseous defects in monkeys following placement of a biocompatible, porous polytetrafluorethylene membrane. METHODS: In each of 8 Taiwan monkeys, 2 maxillary and 2 mandibular teeth were selected for experimentation. Using a diamond bur, 3-walled osseous defects were created on the distal of the maxillary cuspid and the mesial of the mandibular second bicuspid of one side. Two-walled (lingual wall and proximal wall) osseous defects were created on the contralateral side. After root planing, teflon membranes were applied to the mandibular test teeth. In the maxilla, all procedures were the same except for the placement of teflon membranes. Two monkeys were sacrificed 3, 6 and 9 months after operation and prepared for histologic and histometric evaluation. Reentries were performed while the other 2 monkeys were terminated 11 months after operation. RESULTS: Histologic evaluation revealed that new connective tissue attachments were found to a greater extent in the 3-walled periodontal osseous defects treated with teflon membranes compared with the non-membrane sites (p = 0.05). More periodontal regeneration was not predictably obtained in the surgically created 2-walled osseous defects when the teflon membranes were used. CONCLUSIONS: For 3-walled periodontal osseous defects, guided tissue regeneration was superior to conventional periodontal flap surgery. For 2-walled defects, new connective tissue attachment could not be predictably achieved. PMID- 7982131 TI - Characteristics of the ventilatory load with different ventilatory training devices. AB - BACKGROUND: The characteristics of the load on the ventilatory muscles during breathing with different ventilatory muscle training devices have not been quantified, which may profoundly affect the nature of the training stimulus and the clinical outcome of the ventilatory muscle training. METHODS: In four normal males, we continuously measured mouth pressure, esophageal pressure, tidal volume, breathing frequency (fb), minute ventilation (VE), inspiratory time, duty cycle, tension time index (TTI), and total respiratory work (WTOT) during 10 seconds' maximum ventilatory maneuvers. Maximum breathing was performed at 3 fb's (20, 60 and 88 breaths/min) with each of 3 different inspiratory loading devices: 1) Isocapnic hyperpnea (H) with an orifice of 2 (H2) and 1 (H1) cm; 2) Resistive breathing through a Pflex using 3 orifices of diameter 0.54 cm (P1), 0.40 cm (P3) and 0.22 cm (P5); 3) A threshold loading device (T) set at 10 (T10) and 25% (T25) of the previously measured maximum inspiratory mouth pressure. RESULTS: Pflex could provide higher TTI and lower VE, compared with the other 2 devices, at the breathing frequencies of 60 and 88 breaths/min (p < 0.05). Pflex with smaller orifices (P3 and P5) could exaggerate this difference (p < 0.01). WTOT increased significantly as fb increased from 20 to 88 with H1, H2, T10, T25 and P1 (p < 0.02), but not with P3 and P5. VE showed a better correlation with WTOT than TTI did (p < 0.001, r = 0.863 vs p > 0.1, r = -0.365). CONCLUSIONS: High flow, high WTOT and low tension loads were provided by H2, H1, T10 and T25 devices whereas low flow, low WTOT and high tension loads were provided by P5 and P3. P1 provided intermediate flow and tension load. PMID- 7982132 TI - Breast cancer and pregnancy. AB - BACKGROUND: Breast cancer developing during pregnancy or lactation is such an infrequent problem that, when it occurs, physicians are confronted with ethical and therapeutic challenges. Moreover, there are very few references to compare or discuss breast cancer in pregnant women in Taiwan. We hope that data from this review will add to our understanding of such difficult problem as well as help improve the treatment of our patients. METHODS: Between 1979 and 1988 the charts of 21 women, who were pregnant or postpartum within one year of the breast cancer diagnosis, were analyzed retrospectively. All of the patients were followed until Dec. 1990. Patients with pregnancy-associated breast cancer were compared with nonpregnant women (199 cases) of similar age who were treated at the same hospital and during the same period. RESULTS: We found no statistical differences in the overall 5-year survival rate between pregnant (57.1%) and nonpregnant (69.6%) groups. It is noteworthy that the time lag was significantly longer in the pregnant group than in the nonpregnant group. A stage-by-stage comparison showed equivalent survival rates between pregnant and nonpregnant patients. The pregnant patients at stage II had a somewhat lower survival rate; however, there was no statistical significance. CONCLUSIONS: The rule of cancer treatment, "early diagnosis followed by aggressive management," is still a key principle to improve the treatment in pregnant women with breast cancer. PMID- 7982133 TI - The clinicopathological spectrum of renal amyloidosis. AB - BACKGROUND: Renal amyloidosis is an uncommon cause of nephrotic syndrome. The clinical conditions in Chinese people remain obscure. This is a retrospective review of the clinicopathological spectrum of 12 cases diagnosed in Taichung Veterans General Hospital from October 1982 to November 1993. METHODS: Charts and renal pathological slides were reviewed retrospectively. A scoring system was set to evaluate the degree of amyloid deposition in the renal tissue. The clinical profile, immunological data, pathological picture and final outcomes are presented and discussed, with literature review. RESULTS: There were 12 cases of primary amyloidosis including 1 case of multiple myeloma. All were confirmed by renal biopsy. The cases were all male with mean age of onset as 53.3 +/- 11.3 (range: 32 to 65 years). The mean follow-up duration was 22.9 +/- 32.8 months. The initial average creatinine clearance was 66.7 +/- 42.7 ml/min; mean daily urine protein was 7.0 +/- 4.1 grams. Nephrotic syndrome was the main clinical manifestation, present in all 12 cases. Other presenting symptoms and signs included: malaise in 7 cases; hypertension and anorexia in 4 cases; limb numbness in 3 cases; low back pain, dizziness and microhematuria in 2 cases each; anemia, headache, stroke, restrictive cardiomyopathy, hepatomegaly, syncope, body weight loss, dysphagia and skin itching in one case individually. Amyloid cardiomyopathy was present in 4 of the 8 patients who received echocardiography. The mean serum albumin level was 1.9 +/- 0.7 mg/dl, globulin level 3.1 +/- 1.1 mg/dl. Urinary Bence-Jones protein examination was performed in 8 cases; none revealed positive response. The mean immunoglobulin (Ig) level for the patients included: IgG 1018 +/- 901 mg/dl, IgA 262.0 +/- 313.8 mg/dl, IgM 104.8 +/- 84.2 mg/dl. There were at least 4 cases with high levels of one Ig but depressed levels in the others. M component was shown by immunoelectrophoresis (IEP) in 90% of the cases. IEP impression in 10 cases revealed 2 cases of IgA lambda, 2 cases IgA kappa, 3 cases IgG lambda and 1 case IgG kappa monogammopathy, 1 case free lambda myeloma and 1 case negative. The ratio of kappa to lambda chain was 3:6. Bone marrow biopsy performed in 8 cases found only 1 case with multiple myeloma, one with amyloidosis; the other 6 cases were unremarkable. Mesangium was the site of heaviest amyloid deposition, followed by tubular basement membrane, artery and interstitium. The median survival time for those whose total score was lower than 3 points was 97.5 months; 3 to 5 points, 14 months; 6 points or more, 18.5 months. The median survival time was 21.6 months and 3-year-survival rate was 32.7%. The 2 cases with long-term survival were of 111 months and 84 months. The possible reason included: 1) Organ-limited renal amyloidosis; 2) Light amyloid deposition; 3) Younger age; 4) Other undetected favorable factors. CONCLUSIONS: 1) Renal amyloidosis is not a frequent diagnosis of nephrotic syndrome in Taiwan, but it should be suspected in every patient over 50 years old with a recent onset of proteinuria. 2) Renal amyloidosis can be diagnosed only by renal biopsy. 3) Primary renal amyloidosis is a disease of poor prognosis. PMID- 7982134 TI - Effect of intravenous calcitriol on platelet intracellular calcium in uremic hemodialysis patients with secondary hyperparathyroidism. AB - BACKGROUND: To investigate the effect of the reversal of hyperparathyroidism on platelet intracellular free calcium ([Ca2+]i) by pharmacological parathyroidectomy with intravenous calcitriol in uremic patients with secondary hyperparathyroidism (2 degrees HPT). METHODS: Serum concentrations of intact parathyroid hormone (I-PTH) were measured by two-site immunometric assay, and platelet [Ca2+]i was assessed using the fluorescent indicator fura-2. Fifteen hemodialysis patients with 2 degrees HPT and serum I-PTH 4 times greater than the normal upper limits, were selected for treatment with intravenous calcitriol 1 microgram thrice weekly for one month. RESULTS: An increase of serum I-PTH (449.17 +/- 52.35 vs 32.52 +/- 1.95 pg/ml) and elevated platelet [Ca2+]i (139.49 +/- 8.78 vs 74.70 +/- 6.48 nM/L) was observed in uremic patients with 2 degrees HPT. Serum I-PTH levels were significantly correlated with platelet [Ca2+]i in uremic patients with 2 degrees HPT (r = 0.736, p = 0.002). The serum I-PTH levels decreased from 449.17 +/- 52.35 to 221.27 +/- 35.66 pg/ml (p < 0.001) and platelet [Ca2+]i fell from 139.49 +/- 8.78 to 97.86 +/- 7.25 nM/L (p < 0.001) after treatment. Fall in platelet [Ca2+]i was related to concomitant reduction in PTH levels (r = 0.572, p = 0.026). CONCLUSIONS: It was concluded that an increase in cytosolic calcium in uremia may be at least in part induced by PTH. Besides, intravenous calcitriol can provide an effective way to suppress elevated serum I PTH and attenuate platelet free calcium in uremia with 2 degrees HPT. PMID- 7982136 TI - Percutaneous transluminal angioplasty of neck vessels. AB - BACKGROUND: Although surgical endarterectomy or bypass is regarded as the treatment-of-choice for extracranial cerebral vascular stenosis, percutaneous transluminal angioplasty (PTA) has its role as an alternative procedure for symptomatic patients refractory to medical therapy and/or for whom surgical treatment is contraindicated. METHODS: Occlusive blood vessels were first identified by neurologic, ultrasonic and angiographic studies. Patients were premedicated with heparin and corticosteroid. From a transfemoral approach, double lumen balloon dilatation catheter was guided across the area of stenosis, and inflated two or three times to produce dilatation. Following PTA, patients received anticoagulants and corticosteroid for a period, and were followed by clinical examination, Doppler blood-flow and angiographic studies. RESULTS: Seventeen patients undergoing 26 procedures were included in this study. The lesions involved subclavian artery in nine cases, common carotid artery in seven, internal carotid artery in five and proximal vertebral artery in five. Digital subtraction angiography (DSA) was done immediately after PTA and showed improvement of stenotic segment (residual stenosis < 30%) in 22 vessels. Restenosis occurred in two cases of subclavian artery PTA six months later. There were three complications, including TIA in two cases and hematoma at the puncture site in one case. Clinically, symptomatic improvement was obtained in 13 cases. CONCLUSIONS: In patients with significant atherosclerotic stenosis of neck vessels, PTA is a beneficial procedure for improving blood flow to brain circulation and for alleviating symptoms. PMID- 7982135 TI - Comparison between skin testing and in vitro testing for diagnosis of allergen in asthmatic children. AB - BACKGROUND: This study was designed to compare the skin testing and in vitro testing for the diagnosis of most common inhalant allergens in asthmatic children. METHODS: Sixty-two asthmatic children positive to most common allergens in the area of skin tests and multiple allergosorbent chemiluminescent assay (MAST-CLA) were subjected to another Pharmacia CAP test (CAP). RESULTS: The agreement between the results of MAST-CLA and CAP was variable. The correlation coefficient for CAP with MAST-CLA was significant for five allergens except candida, dog dander and Willow pollen when the diagnostic levels of MAST-CLA and CAP were compared with skin test reactions. For all the allergens tested, MAST CLA showed a sensitivity of 51%, a specificity of 84% and an efficiency of 73%, compared with 57%, 80% and 74%, respectively, in the CAP analysis. CONCLUSIONS: MAST-CLA and CAP can be used as a screening test to measure allergen IgE level. Both MAST-CLA and CAP were comparable in their ability to diagnose of allergy to tested allergens. PMID- 7982137 TI - The interaction of diazepam with vecuronium: a clinical study. AB - BACKGROUND: Diazepam, known to possess myorelaxation property, has been widely used clinically to control muscular rigidity and spasticity. The interactions of diazepam with neuromuscular blocking agents have been extensively studied, yet the results reported are somewhat controversial and inconclusive. METHODS: The interaction of diazepam with one of the neuromuscular blocking agents, vecuronium, was studied in 20 ASA I-II patients undergoing elective surgery. They were randomly assigned to two groups with ten in each group. Anesthesia was induced with fentanyl, thiopental and vecuronium and maintained with 1% halothane and 70% N2O in O2. The experimental group received diazepam (0.2 mg/kg) 3 minutes prior to vecuronium (0.1 mg/kg) during induction while the control group received vecuronium (0.1 mg/kg) straight without diazepam. Control records of the integrated electromyography showed the response to train-of-four supramaximal stimulation by a Datex Relaxograph during induction. In no time when the first twitch (T1) recovered to 25% of the control, it was topped up again with another intraoperative dose of vecuronium (0.025 mg/kg). From the derived data, the following parameters were calculated and analysed: (1) onset time T10 (the time from the end of injection of vecuronium during induction to depression of T1 to 10% of control twitch height); (2) duration time T25 (the time from administering vecuronium during induction to the time when T1 recovered to 25% of the original twitch height); (3) topup time T25-25 (the time from administering the top dose of vecuronium to the time when T1 returned to 25% of control twitch height again) and (4) recovery time T25-50 (the time of recovery of T1 from 25% to 50% of the control twitch height at the end of the operation). RESULTS: Significant differences between both groups were found in T10 (221.8 +/- 62.2 vs 135.4 +/- 23.3 sec, p < 0.01) and T25 (41.9 +/- 10.2 vs 50.6 +/- 9.4 min, p < 0.05). The results of T25-25 and T25-50 did not differ much (26.6 +/- 6.9 vs 29.3 +/- 4.4 min, p > 0.05 and 15.0 +/- 8.9 vs 16.9 +/- 8.7 min, p > 0.05 respectively). CONCLUSIONS: The administration of diazepam (0.2 mg/kg) three minutes prior to vecuronium (0.1 mg/kg) during induction may hasten the onset of vecuronium and prolong its duration of action. PMID- 7982138 TI - Spontaneous rupture of the liver associated with pregnancy: a report of two cases. AB - Spontaneous rupture of the liver associated with pregnancy is a rare and grave complication, usually occurring in preeclampsia or eclampsia. Two cases of ruptured subcapsular hematoma of the right liver during pregnancy are reported. The first case was a 19-year-old woman who had suffered from epigastralgia and absent fetal heart beat in the 32nd week of gestation. The second case was a 31 year-old female who complained of nausea and right upper quadrant pain in the 35th week of pregnancy. Both had preeclampsia, and developed shock with disseminated intravascular coagulation soon after admission. Both received surgery and were found to have ruptured hematoma over the right liver. Finally, the first patient died of renal failure, but the second survived because preoperative diagnosis had been exact. Greater suspicion, then awareness of diagnosis can lead to better timing of surgery and an improved prognosis for mother and child. PMID- 7982139 TI - Cytomegalovirus-associated gastric ulcers in a normal host: a case report. AB - Cytomegalovirus (CMV) is an ubiquitous organism, recognized as an important pathogen in patients from the neonatal period through adulthood. Although CMV infections in the gastrointestinal tract of immunocompromised individuals have been reported in increasing frequency in recent years, there have been only a few reports of CMV infections in the gastrointestinal tract of normal hosts. Here a 43-year-old female is described; she had had a four-month history of epigastric pain, and an upper gastrointestinal endoscopy revealed multiple gastric ulcers. Histologic examination of biopsies from the ulcers showed cytomegalovirus inclusion bodies. She had no detectable immunological abnormalities, blood transfusion or organ transplant history. Conventional antiulcer treatments achieved no response. PMID- 7982140 TI - Adrenal adenoma with primary aldosteronism in a child: a case report. AB - Primary aldosteronism caused by an aldosterone-producing adrenal adenoma was documented in an 11-year-old girl who presented with persistent hypertension, headache, tinnitus and hypokalemia. Elevated plasma aldosterone concentration (PAC) (45.5 ng/dl) and suppressed plasma renin activity (PRA) (< 0.3 ng/ml/hrs) were detected. Saline infusion test and postural test helped to confirm the diagnosis. The tumor site was localized by magnetic resonance imaging (MRI). Surgical removal of the tumor yielded dramatic improvement in blood pressure; PAC and PRA returned to normal range. This rare case illustrates the feasibility of recognition and localization of adrenal adenoma in children. The high cure rate by surgical excision warrants careful screening of hypertensive patients with this entity. PMID- 7982141 TI - Histiocytosis X involving thyroid gland: a case report. AB - Diffuse histiocytosis X involving thyroid gland is rare. A 10-year-old boy with progressively enlarged neck mass, skin rash over scalp and face, splinter hemorrhage, otitis externa, episodes of pneumothorax and abnormal liver function was hospitalized. Thyroid scan showed a nonfunctioning mass in the right lobe of the thyroid and needle aspiration biopsy suspected histiocytosis X. Right thyroid lobectomy was performed and revealed histiocytosis X in light and electron microscopic examinations. PMID- 7982143 TI - Electroejaculation for the treatment of idiopathic anejaculation: a case report. AB - Electroejaculation to produce semen from anejaculated males has been employed successfully in conjunction with intrauterine insemination (IUI), in vitro fertilization/embryo transfer, and gamete intrafallopian transfer. We herein report the use of IUI to achieve pregnancy following electroejaculation in a patient with primary idiopathic anejaculation. This 30-year-old patient had a history of anejaculation that was noted after marriage, but had normal sexual potency and occasional nocturnal emission. Electroejaculation was successfully used to obtain semen. The highly motile sperm was recovered from swim up procedure and used for IUI. The 25-year-old wife was given clomiphene citrate and Pergonal for ovulation induction. A triplet pregnancy was achieved. At 26 weeks of gestation, the first triplet was delivered after spontaneous rupture of membrane. We tried to delay delivery of this retained twin pregnancy. Thirty-two days later, the remaining two fetuses were delivered weighing 1100 gm and 900 gm. Ninety-three days after delivery, these two babies were discharged, putting on weight to 3564 gm and 3264 gm. This case represents the first success of using electroejaculation to achieve pregnancy from anejaculated patient in Taiwan. PMID- 7982142 TI - Gastric lymphoepithelioma-like carcinoma associated with Epstein-Barr virus proved by in situ hybridization study: a case report. AB - Undifferentiated gastric carcinoma with prominent lymphoid infiltration and a striking resemblance to nasopharyngeal lymphoepithelioma has rarely been reported. Recently, the Epstein-Barr virus (EBV) genome has been demonstrated in some cases of gastric carcinoma with a morphology similar to undifferentiated nasopharyngeal carcinoma (NPC). One such case has been identified here by immunohistochemistry; it was explored for the EBV genome by RNA in situ hybridization (ISH) with an EBERs (Epstein-Barr virus encoded RNAs) probe. EBV RNAs were detected uniformly in the carcinoma cells or adjacent dysplasia epithelium, but were not present in the related lymphoid infiltration or in normal gastric mucosa. These findings add to the growing body of evidence suggesting the strong association of EBV with gastric lympho-epithelioma-like carcinoma (LELC), and also indicate that a latent EBV infection may play a role in undifferentiated epithelial cells. PMID- 7982144 TI - Whither surgical oncology? PMID- 7982145 TI - Sacral bone tumours. PMID- 7982146 TI - Limb salvage for bone sarcomas. PMID- 7982147 TI - [Pancreatic pseudocyst: Evolution of therapeutic concepts]. AB - OBJECTIVE: To reassess the therapeutic options for pancreatic pseudocysts, resulting from the refinement of imaging techniques of the pancreas over the past 15 years. DATA SOURCES: An extensive review of the literature for the period 1970 to 1994. When pertinent, the authors' experience with 45 patients was added to the literature data. STUDY CRITERIA: In the literature review the following selection criteria were used: diagnostic modalities (clinical, endoscopic and radiologic); clinical context (etiology and clinical presentation); and therapeutic modalities (observation and drainage). DATA EXTRACTION AND SYNTHESIS: Data collection was retrospective in most series. Whenever possible data collected before 1980 were differentiated from those collected after 1980 because diagnostic modalities were quite different in these two periods. CONCLUSIONS: Pancreatic pseudocysts are now diagnosed with more certainty and followed with more precision. Long-term observation is a safe and valuable approach. In symptomatic patients, some form of drainage should be considered. In an elective situation, internal drainage (endoscopic or surgical) is favoured. Cystogastrostomy should not be associated with an increased risk of bleeding. PMID- 7982148 TI - Meta-analysis of highly selective vagotomy versus truncal vagotomy and pyloroplasty in the surgical treatment of uncomplicated duodenal ulcer. AB - OBJECTIVE: To compare critically by meta-analysis the postoperative outcomes after truncal vagotomy and pyloroplasty (TVP) and after highly selective vagotomy (HSV). DATA SOURCES: A search was conducted on MEDLINE with the keywords "peptic ulcer" and "vagotomy". Bibliographics of the articles retrieved and review articles pertaining to the subject were scanned further. STUDY SELECTION: Included were only published prospective, randomized controlled trials comparing TVP and HSV in the English-language literature up to April 1991. Twelve studies were found. DATA EXTRACTION: Two authors, working independently, abstracted raw data on mortality, recurrence, dumping, diarrhea and postoperative Visick grading. DATA SYNTHESIS: A ratio greater than 1.0 indicates a higher proportion occurring with TVP and less than 1.0 a higher proportion with HSV. [Table: See Text] CONCLUSION: The results suggest that the likelihood of adverse long-term sequelae is higher with TVP whereas the likelihood of recurrence is higher with HSV. PMID- 7982149 TI - Parathyroid cancer: clinical variations and relationship to autotransplantation. AB - OBJECTIVE: To identify the clinical and pathological characteristics of parathyroid cancer to determine the best method of treatment and to prevent the use of malignant tissue for autotransplantation. DESIGN: A chart review over a 20 year period (1973 to 1993). SETTING: Two tertiary-care referral centres in Ontario with specialty interest in disease of the thyroid and parathyroid glands. PATIENTS: Sixteen patients, identified as has having parathyroid cancer (equivocal diagnosis in 9 and definitive diagnosis in 7). MAIN OUTCOME MEASURES: The clinical and histologic features, treatment, morbidity and mortality of parathyroid cancer. RESULTS: Some patients with an equivocal diagnosis had postoperative recurrent hyperparathyroidism characterized by multiple soft-tissue implants of parathyroid that persisted after reoperation. The others had infiltrative attachment of parathyroid lesions to the thyroid gland and were eucalcemic and disease free up to 12 years after treatment. Three of the seven patients with a definitive diagnosis of parathyroid cancer were treated for a neck mass; the others were treated for hypercalcemia and multiple lytic bone lesions, hypercalcemia and renal disease and secondary hyperparathyroidism. En bloc resection, carried out in all but one case, was curative in five cases. The patient with secondary hyperparathyroidism underwent total parathyroidectomy and autotransplantation but died of metastatic parathyroid cancer 1 year later. CONCLUSIONS: Because of the difficulty in making a histologic diagnosis of parathyroid cancer, en-bloc resection of the thyroid and parathyroid glands and locally invaded structures is the appropriate treatment to avoid tumour spillage. Caution should be exercised in the use of donor parathyroid tissue for autotransplantation. PMID- 7982150 TI - Diagnosis and management of sacral bone tumours. AB - OBJECTIVE: To evaluate the efficacy of current treatment in patients with sacral bone tumours. DESIGN: Retrospective case series. SETTING: A quaternary care unit within a teaching hospital. PATIENTS: Twenty-nine patients with sacral tumours referred to the unit between 1983 and 1991. Follow-up was a minimum of 18 months. INTERVENTIONS: Diagnostic biopsy in all patients. Plain radiography, ultrasonography, computed tomography (CT), magnetic resonance imaging (MRI) and bone scanning. Sacral resection in patients with malignant or aggressive primary bone tumours. MAIN OUTCOME MEASURES: The accuracy of biopsy and local and systemic recurrence of the disease. RESULTS: Symptoms were present for a mean of 12 months to the time of presentation. Low-back pain was present in 28 of 29 patients. Radicular pain and sacral nerve dysfunction were found more often in patients with malignant tumours. Only three patients had altered bowel habits. On rectal examination a mass was palpable in 61% of patients. The sacral abnormality was demonstrated by plain radiography in 6 of 9 cases, by ultrasonography in 2 of 7 cases, by bone scanning in all of 17 cases, by CT in 24 of 25 cases and by MRI in 17 of 18 cases. Fine-needle aspiration biopsy provided the correct diagnosis in only one of four patients. Transrectal biopsy resulted in tethering of the rectum to the tumour in two patients. Core needle biopsy gave an accurate diagnosis in eight of nine patients. Open biopsy was repeated to obtain adequate tissue in 3 of 19 patients.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7982151 TI - Limb salvage surgery for widely infiltrating bony sarcomas. AB - OBJECTIVE: To determine whether neoadjuvant chemotherapy and radiotherapy for bony sarcomas extending into soft tissues would allow limb salvage yet maintain local disease control. DESIGN: A prospective cohort study. SETTING: A university affiliated cancer centre in Alberta. PATIENTS: All patients with potentially curable, widely infiltrating bony sarcomas of the extremity without neurologic deficit, referred to the centre in the 6 years from January 1984 to December 1990. There were 11 patients; 1 did not complete the protocol. The mean follow-up was 24 months. INTERVENTIONS: Adriamycin (doxorubicin) was infused for 3 days at a rate of 30 mg/d. A few days later radiotherapy was given 5 days a week for 10 doses at a rate of 3.0 Gy per dose. Four to 5 weeks later the tumour was excised surgically, with placement of a bone allograft or prosthesis, allowing a 1-cm margin of healthy soft tissue and a 5-cm margin of healthy bone and marrow cavity whenever possible. MAIN OUTCOME MEASURES: Need for limb amputation, infectious complications, recurrence of local or regional disease. RESULTS: One patient underwent amputation after fracture through the tumour site. There were two postoperative infections, one acute and one chronic. All patients had full neurologic function of the distal limb. There was no local or regional recurrence of disease. CONCLUSION: Neoadjuvant chemotherapy followed by radiotherapy and tumour excision provides control of aggressive local bone sarcomas while maintaining limb integrity. PMID- 7982152 TI - Pilomatrixoma: a common, benign childhood skin tumour. AB - OBJECTIVE: To review recent experience with pilomatrixoma, particularly with respect to diagnosis. DESIGN: Chart review for an 8-year period. SETTING: A university-affiliated children's hospital. PATIENTS: Fifty children with 51 histologically proven pilomatrixomas. INTERVENTION: Excision of the lesion. MAIN OUTCOME MEASURES: Clinical presentation, diagnosis and pathological findings. RESULTS: The clinical presentation was typically that of an asymptomatic superficial mass that increased slowly in size and was located in the head and neck (78%) or chest and upper limbs. In one case the mass increased rapidly over 2 weeks and changed in colour from red to purple with areas of pink and tan. The referring diagnosis was incorrect in 94% of cases, and the preoperative diagnosis was incorrect in 57%. Pathologically the tumours were situated in the dermis or subcutaneous tissue. None were cystic, but several had areas of calcification. None of the tumours recurred after excision, but two patients had multiple lesions at different locations and times. CONCLUSIONS: Pilomatrixomas in children are simple to treat successfully but have variable clinical presentation. Early diagnosis is important so that unnecessary, aggressive surgery can be avoided. PMID- 7982153 TI - Selective surgical management in penetrating neck injuries. AB - OBJECTIVE: To evaluate selective operative management in penetrating neck trauma. DESIGN: A chart review. SETTING: A university-affiliated hospital in Johannesburg, South Africa. PATIENTS: All adults admitted to the hospital between January 1988 and June 1993 with a penetrating neck wound. Excluded were patients in whom there was no suspicion of an occult injury that might need further investigation. There were 755 patients in the study. INTERVENTIONS: Immediate surgical exploration (group A, 613 patients) and observation with constant monitoring (group B, 142 patients). MAIN OUTCOME MEASURES: Unnecessary explorations in group A and missed significant injuries in group B. RESULTS: In group A there was a 3% incidence of unnecessary explorations, and 4.2% of the patients died. In group B there was a 9.1% incidence of missed injuries, and 2.8% of the patients died as a result of the delayed diagnosis. Overall the death rate was 4%. CONCLUSION: Selective operative intervention for penetrating neck trauma results in fewer negative explorations and a death rate comparable to those of series that support mandatory neck exploration. PMID- 7982154 TI - Testicular juvenile capillary hemangioma: conservative management with frozen section examination. A case report. AB - Juvenile capillary hemangioma, an exceptionally rare benign neoplasm, seen in an 18-year-old patient, was managed in an unorthodox fashion. The patient insisted on a conservative approach to the management of his tumour. In an effort to comply with his wishes, frozen-section examination of the tumour was carried out. The astute observations of the pathologist who recognized the juvenile capillary hemangioma made possible a conservative surgical excision and testicular repair. The case illustrates some of the difficulties that may be encountered in the successful management of testicular tumours. PMID- 7982155 TI - Perforated colonic carcinoma mimicking perforated peptic ulcer: an argument for full exploration of the stomach and duodenum. AB - Perforated peptic ulcer is one of the commonest types of hollow-viscus perforation. Because many of these ulcers are found at laparotomy to be sealed off, some authors believe it is unnecessary to dissect the surrounding tissue from the presumed site of perforation. A patient with a long history of peptic ulcer disease experienced the sudden onset of signs and symptoms of perforated peptic ulcer. On exploration, the omentum appeared to be densely adherent to the pylorus and duodenum. However, no perforation was found when the omentum was dissected free from the stomach and duodenum. Further exploration revealed a walled-off, perforated carcinoma of the transverse colon adjacent to the mesenteric border. As a result of this experience, the authors emphasize that when the findings at operation do not fit the clinical presentation in a patient with a presumed perforated peptic ulcer, a thorough exploration of the abdominal viscera is mandatory to identify the pathologic process. PMID- 7982156 TI - Large cell, calcifying, Sertoli cell tumour: a case report. AB - Large cell, calcifying, Sertoli cell tumour, because of its distinct pathological and clinical presentations, has recently been recognized as a variant of Sertoli cell tumour. A 26-year-old man with this tumour is described, with a 3-year follow-up. Large cell, calcifying, Sertoli cell tumours occur mostly in young people. At least 6 of the 14 cases reported in the literature were associated with endocrine disorders or cardiac myxoma, or both. The patient described in this report had no endocrine or other disorders. PMID- 7982157 TI - Foreign-body abscesses presenting as soft-tissue tumours: two case reports. AB - Foreign bodies in the extremities often present as bony extensions of soft-tissue masses. Wooden foreign bodies can be detected by computed tomography and magnetic resonance imaging, but these studies are often nonspecific and cannot detect small bodies. As illustrated by two cases reported in this paper, these masses are difficult to distinguish from primary soft-tissue sarcomas when the history and imaging findings suggestive of a foreign-body reaction are absent. PMID- 7982158 TI - So many ways to think. An overview of approaches to ethical issues in geriatrics. AB - This article provides an overview of ways to think about ethical issues in geriatrics. Principle-based approaches include deontology, utilitarianism, virtue theory, and natural law. Case-based approaches include casuistry, care, and narrative ethics. Pragmatism and feminism are methods that mesh case-based with principle-based considerations. Each of these approaches is explained and critiqued in relation to specific cases in geriatrics. The author concludes that clinical ethical decisions are optimized by considering, but not necessarily following, all of the available approaches to ethical dilemmas. PMID- 7982159 TI - The life and death of Miss Mildred. An elderly black woman. AB - Who is the elderly black woman? What do health care providers need to know about her life when they treat her for her numerous chronic ailments? What social factors are important when those chronic illnesses ultimately require decisions about withholding or withdrawing treatment? This article presents the life story of Miss Mildred: a composite of the history, family, community, religion, work, health, and death of an elderly black woman in the rural south. What providers know about elderly blacks comes from the expert; this article lets Miss Mildred speak for herself. PMID- 7982160 TI - Advance directives and the patient self-determination act. AB - Advance directives cover a wide variety of situations concerning the advance planning for medical care. Advance directives have existed for approximately 20 years; however, their forms and uses are presently expanding and evolving. This article presents advance directives, their various forms and uses, and reviews the current data on how well they achieve their desired goal. The Patient Self Determination Act, which was designed to promote the acknowledgment and completion of advance directives, is also discussed, as well as practical suggestions for the current and future uses for advance directives. PMID- 7982161 TI - Surrogate decision making. Who will make decisions for me when I can't? AB - The necessity of surrogate decision making arises for geriatric patients who can no longer make decisions for themselves. Almost every clinical situation involves some assessment of a patient's decisional capacity. Because decisional capacity is decision specific and entails the ability to manipulate information, it is best to conduct functional evaluations and use psychiatric measurements for dementia cautiously in determining decisional capacity. Traditionally, the medical community has relied on family members to be surrogate decision makers when a patient is assessed as decisionally incapacitated. That practice still has moral warrant, even amid advocacy for the use of advance directives, because most people have not completed such planning instruments. The family as a primary social unit is likely the most concerned for the welfare and wishes of the patient. These theoretical grounds are supplemented by emerging empirical evidence that elderly patients themselves almost always prefer that family members serve in the role of surrogate decision makers. Dealing with family surrogates obliges the geriatrician to ensure that failures in communication do not arise and that conflicts of interest are avoided in protecting the best interests of the patient. Although recent legal climate has shown a preference for a substituted judgment standard in surrogate decision making, medical concern for the best interests of the patient, together with empirical evidence that the elderly are most interested in decisions that arise out of trusted interdependencies, suggests that rules and laws are no substitute for the good faith human actions of trusted surrogates. PMID- 7982162 TI - Dialysis decisions and the elderly. AB - It is ironic that the patients who were specifically excluded from dialysis at its inception, the elderly, are now the fastest growing segment of the dialysis population. Just because it is possible to dialyze elderly patients does not mean that it should be done. This article reviews the following topics as they relate to decisions about dialysis treatment in elderly people--medical outcomes, age as a selection criterion, allocation of scarce resources, and withholding and withdrawing dialysis--and presents an approach to reaching decisions about treatment of renal failure in the elderly. PMID- 7982163 TI - Tube-feeding decisions in the elderly. AB - Tube-feeding decisions in the elderly can be most challenging. We begin our decision making with the premise that artificial nutrition is a medical therapy and therefore that its prescription is based on a calculation of net benefits over burdens for the patient to whom it is given. When the burdens of this therapy outweigh the benefits of prolonged life, tube feeding may be ethically withheld or withdrawn. For the cognitively impaired and in the absence of known patient preferences, the ratio of benefits to burdens may best be figured after a time trial of therapy. If restraints are needed to keep the tube in place, or if significant medical complications ensue, the burdens of the therapy have outweighed its potential benefits, and the therapy may be ethically withdrawn. State statutes and institutional policies are often confusing and at times in conflict with the ethical choice made by families and health care providers for their loved ones and patients. The options--starting a court battle (Cruzan7), moving the patient to a different state (Busalacchi), or committing civil disobedience--are not best for the welfare of the patient, family, or health care team. We well recognize that what is legal is not always what is ethical. Ethics should lead the law as we consider how to use new health care technologies wisely. We hope that the state legislatures will work to minimize future conflicts by acknowledging that (1) artificial nutrition is a life-sustaining therapy that should not have special status distinct from other life-sustaining therapies and (2) artificial nutrition and hydration are medical therapies that can and should be ethically withdrawn or withheld when their burdens outweigh their benefits. PMID- 7982164 TI - Ethics and long-term care. Everyday considerations. AB - This article deals with ethical issues intrinsic to long-term care, emphasizing those that relate to the daily practice of the physician. First, some general issues are considered, followed by a brief discussion of nursing home care and home care, the two most common service systems that apply to patients receiving long-term care. For the most part, this article focuses on the ethical issues involved for patients who live with such care rather than those concerning the death of long-term care clients. The author argues that the balance needs to shift to more attention to these everyday matters. PMID- 7982165 TI - Ethical aspects of guardianship. AB - One important device that has evolved within the legal system for dealing with the problem of cognitively incapacitated individuals and the concomitant need for some form of surrogate decision making on their behalf is guardianship. This article outlines the most salient ethical challenges related to guardianship for clinicians who interact professionally with older persons of diminished capacity and their families. Special attention is devoted to the clinician's role in initiating guardianships, questioning the guardian, in the guardianship proceeding, and evaluating the therapeutic impact of guardianship. PMID- 7982166 TI - Untying the elderly. 1989 to 1993 update. AB - Research and public policy pertaining to the use of physical restraints has advanced since Evans' and Strumpfs' 1989 review. Research better delineates the harms caused by restraints, although not finding benefits. Federal law sharply restricts the use of restraints. Legal liability weighs against the use of restraints in most instances. Nursing homes have published substantial experience with programs to reduce and eliminate the use of physical restraints. PMID- 7982167 TI - Managed competition and managed care. What are the ethical issues? AB - Managed competition and managed care, two hallmarks of President Clinton's health care reform proposal, would significantly change the way that health care in the United States is structured and delivered. This article presents ethical debates about managed care in historical perspective, reviews ethical arguments for and against managed care systems, and concludes with a set of practical guidelines to govern existing managed care arrangements. Throughout the paper, special attention is devoted to the impact of managed care on the elderly population and on physician-patient relationships. PMID- 7982168 TI - Quality of life. Considerations in geriatrics. AB - Conceptual and ethical considerations guiding discussions of quality of life and the elderly are examined. The relationship of quality of life to function and health status is assessed and the conclusion reached that the meaning of quality of life changes over the life span. Finally, the presentation is made of the ethical implications for clinical practice and policy of differences in definition of quality of life. PMID- 7982169 TI - Screening for prostate cancer. PMID- 7982170 TI - Imaging of brain tumors. PMID- 7982171 TI - Nasopharyngeal lymphoid tissue masses in patients with human immunodeficiency virus-1. Histologic findings and clinical correlation. AB - BACKGROUND: Although the histologic changes in lymph nodes in patients infected with the human immunodeficiency virus-1 (HIV-1) are well described, the histology and resulting clinical symptoms of hyperplastic nasopharyngeal lymphoid tissue (NPLT) in these patients are not widely known, particularly to pathologists and oncologists. METHODS: Nine patients with HIV-1 presented with a nasopharyngeal mass, nasal stuffiness, nasal bleeding, hearing loss, and cervical lymphadenopathy in various combinations. Tonsillar tissue was biopsied or removed from all nine. RESULTS: The tonsillar tissue showed a spectrum of the changes of reactive lymphoid hyperplasia. CONCLUSIONS: Clinicians and pathologists must be aware of the spectrum of histologic changes and clinical features relating to biopsies from NPLT to interpret the changes correctly and to avoid a misdiagnosis of malignant lymphoma. PMID- 7982172 TI - High prevalence of p53 protein overexpression in patients with esophageal cancer in Linxian, China and its relationship to progression and prognosis. AB - BACKGROUND: Linxian is the highest endemic area of esophageal squamous cell carcinoma (ESCC) in China and one of the highest incidence areas in the world. The relationship of p53 protein accumulation to geographic variation, pathologic findings, and prognosis has not been investigated extensively. METHODS: Formalin fixed, paraffin embedded ESCC tissues from 100 patients who underwent esophagectomy between 1973 and 1983 were immunostained by using monoclonal antibody pAB1801. RESULTS: p53 overexpression was observed in 41 (87.2%) of 47 tumors of patients in Linxian and in 16 (64%) of 25 additional patients outside Linxian. Its prevalence in the noncancerous epithelium (11/72, 15.3%) and carcinoma in situ (1/7, 14.3%) was lower than that in invasive lesions (64/93, 68.8%). Its immunostaining intensity increased with the depth of cancer invasion. Of 30 primary carcinomas with lymph node metastasis, 29 (96.7%) were positive. However, only 36 (51.4%) of 70 primary lesions without metastasis were positive, and a higher intensity was noticed in the metastases. There was a lower expression rate in tumors of patients surviving more than 10 years (25/52, 48.1%) than in those surviving less than 3 years (40/48, 83.3%). Overall and nonadvanced or metastasis-free cumulative survival rates were both significantly different in patients with and without p53 protein overexpression. CONCLUSIONS: There is a higher expression rate of p53 protein in ESCC in tumors of patients from Linxian than in those from the surrounding area. The accumulation of p53 protein is related to the invasiveness and capability for metastases of cancer cells and appears to be a useful prognostic factor for patients with ESCC. PMID- 7982173 TI - Intratumoral injection of a streptococcal preparation, OK-432, before surgery for gastric cancer. A randomized trial. Cooperative Study Group of Preoperative Intratumoral Immunotherapy for Cancer. AB - BACKGROUND: The preoperative intratumoral injection with OK-432 (Picibanil, Chugai Pharmaceutical Co., Tokyo, Japan), an immunomodulatory agent prepared from an attenuated strain of streptococcus pyogenes, activates the regional immune system and causes degeneration of cancer tissue in carcinoma of the stomach. METHODS: A multi-institutional randomized trial of OK-432 to determine its clinical usefulness was conducted. Three hundred and ninety-five patients with gastric cancer were assigned randomly either to receive or not to receive a preoperative intratumoral injection of OK-432. Among them, 277 patients with advanced cancer were treated by common postoperative chemoimmunotherapy consisting of mitomycin C, tegafur, and OK-432. All patients were followed for at least 5 years. RESULTS: The adverse effects of OK-432 injected intratumorally predominantly were mild fever, anorexia, and abdominal pain, however, no treatment was required for these symptoms. Overall, there were no differences in outcome between the OK-432 and control groups. However, analysis based on stage showed that a preoperative intratumoral injection of OK-432 significantly improved the 5-year survival rate of patients with Stage III cancer (P = 0.0229), at 47.7% for the OK-432 group and 27.5% for the control group. In subset analysis, when the 5-year survival of patients with and without tumor infiltrating lymphocytes (TIL) was compared, OK-432 injected intratumorally had a significant positive effect on the group showing a moderate to marked number of TIL (P = 0.0438). CONCLUSION: These results showed that the intratumoral injection of OK-432 may improve survival of patients with Stage III gastric cancer. Cancer 1994;3097-3103. PMID- 7982174 TI - Helix pomatia agglutinin binding is a useful prognostic indicator in colorectal carcinoma. AB - BACKGROUND: Most deaths from colorectal carcinoma are due to metastases. A relatively reliable prognostic indicator at surgery to date is the Dukes' stage, but this is a morphologic approach that does not elucidate biochemical changes to explain why cells became metastatic. The binding sites for the lectin from the Roman snail Helix pomatia (HPA) were shown to be good prognostic indicators in breast and gastric cancer, and accordingly, this study was performed to evaluate the use of HPA binding sites as prognostic markers in colorectal carcinoma. METHODS: The histochemically detected expression of HPA binding sites in colorectal carcinomas (n = 130) was increased. The results of the histochemical findings were correlated with patient survival and tumor recurrence. RESULTS: The results indicated that the prognosis for the groups of patients whose colorectal cancer cells binded to HPA in tissue sections was almost as bad as those with Dukes' Stage C disease. CONCLUSION: Because HPA binds to N-acetylgalactosamine, the authors' results indicate that this sugar residue is at least partly involved in the process of human colorectal carcinoma cells metastasizing to regional lymph nodes and possibly also to distant sites. PMID- 7982175 TI - Molecular genotyping for N-acetylation polymorphism in Japanese patients with colorectal cancer. AB - BACKGROUND: N-acetylation polymorphism has been documented as a representative pharmacogenetic trait, and also has been implicated ecogenetically in an individual's susceptibility to cancer. However, there still remains controversy concerning the association between colorectal cancer and N-acetylation polymorphism. METHODS: A newly established molecular genotyping method using polymerase chain reaction-based restriction fragment length polymorphism to analyze the distribution of polymorphism in a large group of Japanese patients with colorectal cancer was used. RESULTS: Based on an analysis of 234 Japanese patient with colorectal cancer and 329 healthy control subjects, no significant difference was observed in either the distribution of acetylator phenotypes or of allele frequencies between the two groups. In addition, no significant difference in their distribution was found based on the age at which cancer was first detected, the location of tumors, or the histopathologic features. CONCLUSIONS: N acetylation polymorphism does not appear to be implicated crucially as a genetic trait affecting an individual's susceptibility to colorectal cancer. PMID- 7982176 TI - Endoscopic criteria of early squamous cell carcinoma of the bronchus. AB - BACKGROUND: Early lung cancer, not extending beyond the bronchial cartilaginous layer without regional lymph node involvement is considered curable by endoscopic laser therapy or limited surgery. The endoscopic criteria for early squamous cell carcinoma of the bronchus, however, have not yet been determined. METHODS: For 44 resected lesions of roentgenographically occult bronchogenic squamous cell carcinomas, the relationship between endoscopic findings and the degree of histologic extent of tumor was examined. RESULTS: The lesions were divided into three types: polypoid or nodular (PN), flatly spreading (FS), and mixed. Thirty three lesions arising from the central bronchus included 7, 19, and 7 of the PN, FS, and mixed types, respectively. In the central lesions, the degree of transmural invasion and the greatest dimension correlated, but the degree of intramural invasion of PN-type lesions was higher than that of the FS type. The PN-type lesions smaller than 10 mm and the FS type smaller than 15 mm in greatest dimension were found within the cartilaginous layer without regional lymph node involvement. All lesions of the mixed type were larger than 20 mm. Three of the lesions larger than 20 mm had regional lymph node involvement. All 11 lesions originating in the peripheral bronchus were of the FS type, and a lesion of only 5 mm in greatest dimension had extracartilaginous invasion. CONCLUSIONS: The endoscopic criteria of early squamous cell carcinoma of the bronchus may be applied to central PN lesions smaller than 10 mm and central FS lesions less than 15 mm in greatest dimension. Any lesions of mixed type should be excluded from the criteria. PMID- 7982177 TI - Dysplastic nevi as a melanoma risk factor in patients with familial melanoma. AB - BACKGROUND: Familial melanoma has been associated with "clinically atypical moles" or "dysplastic nevi," (DN) which are markers for increased melanoma risk. In addition, melanomas in these kindreds present at a younger age, and tend to be multiple. METHODS: Melanoma incidence rates were determined for 710 members of 311 melanoma families, defined as kindreds in which melanoma had occurred in two or more blood relatives. Patients were classified either clinically or histologically as expressing DN. Melanomas that occurred before the first examination were recorded, and patients were followed prospectively for new melanomas. RESULTS: In prospective follow-up, the age-adjusted melanoma incidence rate was 1710/100,000 patient-years in family members with DN. In contrast, the rate was zero (no melanomas occurred) in family members without DN. For family members with DN, but without a history of melanoma, the age-adjusted incidence rate of melanoma was 413/100,000 patient-years, whereas the rate was 2779/100,000 patient-years in family members with DN and a history of melanoma. CONCLUSIONS: Dysplastic nevi and a history of melanoma are strong risk factors for subsequent melanoma. Prognostic factors are greatly improved for patients with melanomas diagnosed in follow-up compared with the first two melanomas in each kindred. These findings warrant surveillance of individuals with DN who are members of familial melanoma kindreds. PMID- 7982178 TI - Population-based breast cancer survival. Mammographic screening activities in central Italy. AB - BACKGROUND: The aim of this study was to evaluate the effect on 5-year survival of patients with invasive breast cancer relative to demographic and clinical variables (age, residence, and disease diffusion) and to early diagnostic procedures performed in the area. METHODS: The observed (Kaplan-Meier method) and relative 5-year survival in 1263 patients with invasive breast cancer in the Province of Florence, Italy, between 1985-1986 (source: Tuscany Cancer Registry) are presented. The results were compared with those of other European areas and of the Surveillance, Epidemiology, and End Results Program. The Cox model is used to evaluate the effects of age at diagnosis (5-year age groups), disease diffusion (localized, regional, distant, unspecified), residence (Municipality of Florence, screening area, other municipalities), and source of diagnosis (Center for the Study and Prevention of Cancer, hospitals) on observed survival. RESULTS: Observed 5-year survival was 68.4% (Kaplan-Meier method) and relative 5-year survival was 75.4%. Relative survival for patients younger than age 35 at diagnosis was high (82.3%); it decreased slowly from 80.5% in the group of patients 35-44 years of age, to 74.0% in those 65-74 years of age, and steeply decreased to 68.1% in those 75 years of age and older. Relative 5-year survival in Florence was lower only than that observed in Switzerland (Geneva) and in the USA (whites). Five-year prognosis was worse in women 70 years of age or older, in advanced stages, in residents of municipalities not involved in the screening program, and in cases diagnosed in hospitals. The gain in survival may be explained partially by lead-time effect and by length bias due to early diagnosis both in self-referred women and in screening-detected cases. In these cases, though, the better prognosis, although attenuated, persisted after adjustment by disease diffusion. CONCLUSIONS: The results suggest that the early diagnosis of breast cancer in self-referred women affects prognosis, at least concerning 5 year survival. Moreover, although lead-time effect and length bias cannot be excluded in this study, screening by personal invitation may reduce the disadvantage in the survival of patients with breast cancer often observed in rural areas. PMID- 7982179 TI - Carcinomatous meningitis in patients with breast cancer. An aggressive disease variant. AB - BACKGROUND: Carcinomatous meningitis is a rare and often devastating complication in patients with breast cancer, and the treatment is controversial. METHODS: A retrospective analysis of 35 patients with carcinomatous meningitis from breast cancer was performed to define the biology of the disease and to guide treatment. RESULTS: An aggressive variant of breast cancer was revealed: meningeal metastasis complicates less than 3.5% of cases of metastatic breast carcinoma. Sixty-seven percent of these patients had tumors that were lobular or combined lobular/ductal histology; the median intervals from primary treatment to disease recurrence and from recurrence to death were 10.9 and 15 months, respectively. The median survival after diagnosis of carcinomatous meningitis was 77 days. The most significant prognostic factor was the Karnofsky performance status (KP) at presentation of meningeal disease. Patients with a KP greater or equal to 70 survived a median of 313 days, whereas those with a KP of 60 or less survived for a median of 36 days (P = 0.0002). In addition, there was a trend suggesting that the response 2 weeks after treatment was initiated, correlated with survival. CONCLUSIONS: Carcinomatous meningitis from breast carcinoma is an aggressive metastatic complication with a poor prognosis. The authors suggest that patients with a poor KP (< 70) should be treated symptomatically and those with a good KP (> or = 70) should receive more aggressive treatment. The patients' survival in this study compared well with other reports, and yet, only one patient was treated with intraventricular chemotherapy. Therefore, these data question the superiority of intraventricular treatment versus other modalities. PMID- 7982180 TI - Neurologic complications of patients with small cell prostate carcinoma. Report of two cases. AB - BACKGROUND: Primary small cell carcinoma arising in organs other than the lung were thought to be relatively rare. However, with the increasing technical sophistication of pathology departments, tumors with foci of small cell neuroendocrine components are being identified more frequently. The pattern of disease involvement and optimal treatment have yet to be defined. METHODS: Two cases of primary small cell carcinoma of the prostate are described in which patients previously had unreported degrees of central nervous system disease. RESULTS: Approximately 75 cases of small cell carcinoma of the prostate have been reported. Neurologic complications have been reported infrequently, although a variety of neurologic paraneoplastic sequelae have been noted. However, carcinomatous meningitis or development of intraductal tumors without concomitant vertebral bone disease has never been reported. These tumors respond poorly to hormonal therapy alone, and recent reports suggest optimal therapeutic strategies may involve combination hormone and chemotherapy. CONCLUSION: Small cell carcinoma of the prostate must be recognized when it arises de novo or with components of adenocarcinoma because the prognoses and response to treatment differs from the more common adenocarcinomas of the prostate. PMID- 7982181 TI - MIB1 staining index and scoring of histologic features in meningioma. Indicators for the prediction of biologic potential and postoperative management. AB - BACKGROUND: The biology of brain tumors, including cell kinetics, has been studied. Recently, monoclonal antibody to Ki67 (MIB1), a nuclear protein related to cell proliferation, has been analyzed immunohistochemically using tissue prepared from paraffin embedded sections. METHODS: The authors assessed the prognostic usefulness of various histologic indicators of the biologic potential of meningiomas in patients who underwent total resection (Simpson's Grade I and II) by evaluating the time to recurrence as an end point. Forty-three patients with a total of 36 meningiomas and 7 hemangiopericytomas were investigated by immunohistochemical analysis using MIB1. RESULTS: MIB1 staining index (SI) and histologic score were well correlated with the recurrence-free interval (r = 0.6749, P = 0.002 and r = -0.4939, P = 0.027, respectively) and with each other (r = 0.7909, P < 0.001). The MIB1 SI and histologic score in the nonrecurrence group were significantly lower than those in the recurrence/metastasis group (P < 0.001 and P = 0.001, respectively). The values of these indicators showed that as the value increased, so did the recurrence rate. CONCLUSIONS: Evaluation using the MIB1 SI and total histologic score of meningioma is useful in assessing the prognosis as well as postoperative management of these patients. PMID- 7982182 TI - Thallium imaging for brain tumors with results measured by a semiquantitative index and correlated with histopathology. AB - BACKGROUND: The optimal management of patients with brain tumors requires knowledge of the tumor characteristics upon presentation and the discovery of recurrence after therapy. Thallium-201 (Tl-201) chloride has shown varying uptake in tumors, depending on their viability and the type and degree of malignancy. This study explores the diagnostic potential of thallium imaging in patients with brain tumors. METHODS: Forty-three Tl-201 single photon emission computed tomographic scintigrams were performed on 40 patients with intracranial neoplasms, nearly equally divided between patients with no prior treatment and patients who had prior treatment and were suspected to have recurrent tumor and/or radiation necrosis. A thallium tumor index was calculated as the ratio of counts for a region of interest drawn in the lesion area and its mirror image in normal brain tissue. A two-tailed Student's t test was performed to compare the thallium index and histopathologic findings. RESULTS: A value of 1.5 for the thallium tumor index allowed for the best correlation between the prediction of malignancy and the histopathologic results. In the pretreatment group, a thallium tumor index greater than 1.5 correlated with high grade malignancy, and less than 1.5 correlated with either a well differentiated astrocytoma or benign cyst. In the posttreatment group, a thallium tumor index greater than 1.5 correlated with recurrent and/or residual malignant tumor. CONCLUSIONS: For those patients undergoing initial evaluation, the thallium study can help in the differential diagnosis of an intracranial mass lesion and offers confirmation of results of biopsy. For those patients who already have received treatment, the study can be used to detect recurrent or residual tumor. PMID- 7982183 TI - Progress in the treatment of Hodgkin's disease in the United States, 1973 versus 1983. The Patterns of Care Study. AB - BACKGROUND: The prognosis for Hodgkin's disease patients has improved significantly since the early 1960s. The reasons for this improvement are multifactorial. METHODS: In the Patterns of Care Study of the American College of Radiology, national surveys to examine process and outcome of patients treated for Hodgkin's disease in 1973 and 1983 were completed. Data were compared for patients who had Stage I-II Hodgkin's disease and who were treated with radiation therapy alone. RESULTS: Clinical characteristics of the patients in the two different treatment eras were similar. There were important differences in treatment parameters. In 1983 compared with 1973, there was more common use of a dedicated simulator, performance of routine port films, use of linear accelerators, use of individually shaped blocks, and treatment to extended fields. Adequacy of treatment fields also was judged superior in the 1983 study. There were improvements in survival and relapse-free survival for patients treated in 1983 versus 1973. CONCLUSIONS: Improvement in radiation therapy technique is associated with an improved outcome for patients treated for Hodgkin's disease. The national standards have improved during the time from 1973 to 1983. PMID- 7982184 TI - Comparison of the efficacy, safety, and pharmacokinetics of controlled release and immediate release metoclopramide for the management of chronic nausea in patients with advanced cancer. AB - BACKGROUND: The short elimination half-life of metoclopramide necessitates frequent administration for optimal relief of nausea. This study compares a newly developed controlled release preparation of metoclopramide (CRM) and immediate release metoclopramide (IRM) with respect to efficacy, safety, and pharmacokinetics in patients with chronic nausea associated with advanced cancer. METHODS: Thirty-four patients with advanced cancer with nausea lasting more than 1 month and with no evidence of involvement of the gastrointestinal tract, peptic ulcer or gastritis, brain metastases, or metabolic abnormalities were randomized, in a double-blind cross-over study, to receive 40 mg of CRM every 12 hours or 20 mg of IRM every 6 hours for 3 days. Nausea, food intake, and side effects were assessed four times daily. On Day 3, sequential venous samples were taken (12 patients) to determine plasma metoclopramide concentrations. RESULTS: In 29 evaluable patients, the intensity of nausea on Day 3, measured by a 0-100-mm visual analogue scale and 0-3 categoric scale was 15 +/- 17 and 0.6 +/- 0.6 after IRM, versus 8 +/- 9 (P = 0.033) and 0.4 +/- 0.5 (P = 0.055) after CRM, respectively. Visual analogue scale nausea scores recorded by time of day and by day for the 3 treatment days were significantly lower for patients who received CRM compared with those who received IRM (P = 0.047 and P = 0.043, respectively), but categoric nausea scores were not significantly different between treatments by time of day and by day across the 3 treatment days. No differences were observed in caloric intake or side effects between treatments. In a pharmacokinetic analysis, the CRM/IRM ratio for area under the curve0-12 (microgram x hours x L-1), Cmax (microgram/L), and Tmax (hours) was 100%, 98%, and 2.3 fold, respectively. CONCLUSION: Controlled release metoclopramide is safe and effective in managing chronic nausea in patients with advanced cancer. Future studies should focus on characterizing this syndrome more clearly and on determining the optimal dose of metoclopramide and the effects of drug combinations that have proven to be useful in managing chemotherapy-induced emesis (i.e., metoclopramide plus corticosteroids). PMID- 7982185 TI - Cardiopulmonary toxicity of treatment with high dose interleukin-2 in 199 consecutive patients with metastatic melanoma or renal cell carcinoma. AB - BACKGROUND: Administration of recombinant interleukin-2 (rIL-2) can mediate tumor regression in patients with metastatic melanoma and renal cell carcinoma. In response to recent FDA approval of high dose rIL-2 for use in renal cell carcinoma, the authors recent experience with the cardiopulmonary toxicity associated with high dose IL-2 therapy is reviewed. METHODS: The treatment courses of all patients receiving high dose intravenous bolus rIL-2 from January, 1988, until December, 1992, were evaluated for cardiopulmonary toxicity. RESULTS: One hundred ninety-nine patients received 310 courses of treatment. There were no treatment-related deaths. Respiratory distress occurred in 3.2% of the courses, requiring intubation in one patient. Three obtunded patients were endotracheally intubated for airway control. Arrhythmias occurred in 6% of the courses (18 patients) with hypotension developing in two of the 199 patients as a result. Eleven of these patients were retreated and recurrent atrial fibrillation developed in two. One episode of significant ventricular tachycardia was noted. Hypotension occurred in 53% of courses; no patients developed hypotension unresponsive to vasopressors. There were no myocardial infarctions; however, 2.5% of patients experienced elevated creatine phosphokinase levels associated with elevated MB isoenzymes attributed to cardiac toxicity. Only one of these patients developed symptoms. Response rates of 19.6% and 15.7% were noted in patients with renal cell carcinoma and melanoma, respectively. Hypotension requiring vasopressors was associated with a significantly improved rate of response in patients with melanoma compared with patients not requiring vasopressors (23.2% vs. 6.5%, P2 = 0.037). CONCLUSIONS: Although high dose intravenous rIL-2 therapy can be associated with cardiopulmonary toxicity, toxic side effects generally are not severe and are rapidly reversible. PMID- 7982186 TI - One hundred neuroblastomas detected through a mass screening system in Japan. AB - BACKGROUND: In Japan, a nationwide mass screening (MS) program for preclinical detection of neuroblastoma in infants was done by measuring urinary vanillylmandelic acid and homovanillic acid at the age of 6 months. In this study, clinical, histopathologic, and biologic features of 100 neuroblastomas detected through the Japanese MS are presented. METHODS: Clinical data of the MS cases were collected and histologic and biologic studies performed on the surgically resected neuroblastomas. Histopathologic evaluation was done including the Shimada classification (all tumors), N-myc oncogene status (58 tumors), and ploidy analysis (31 tumors). The serum ferritin level was measured before surgical intervention in 27 cases. RESULTS: The primary tumor sites of these cases were adrenal (69), retroperitoneum (21), and mediastinum (10). The tumors were clinical Stage I (31), II (31), III (19), IV (8), and IV-S (9); two children had bilateral primary adrenal tumors. Ninety-three percent (93/100) had favorable histology; 100% (58/58) had nonamplified N-myc oncogene expression; 81% (25/31) showed a favorable ploidy pattern, and 96% (26/27) had normal serum ferritin levels. To date, all children in this series are alive and well, although a total of 13 tumors were associated with one or two poor risk factors; 6 had unfavorable histology (UH), 5 had an unfavorable ploidy (UP) pattern, one had UH and UP, and one had an elevated ferritin level. CONCLUSIONS: The majority of neuroblastomas detected through the MS showed favorable biologic factors (biologically favorable group). However, there was a small group with histopathologic and/or biologic unfavorable factors. Patients with unfavorable factors apparently benefit most from early surgical intervention. PMID- 7982187 TI - Transient, severe hyperlipidemia in patients with acute lymphoblastic leukemia treated with prednisone and asparaginase. AB - BACKGROUND: Corticosteroids and asparaginase inhibit protein synthesis. Many of their side effects are familiar to oncologists. Conversely, the possibility of therapy-induced hyperlipidemia generally is not appreciated. The incidence of severe hyperlipidemia during therapy of patients with acute lymphoblastic leukemia (ALL) who received prednisone and asparaginase was evaluated. METHODS: During therapy with prednisone and asparaginase, a 10-year-old girl with precursor B ALL was identified with a peak plasma triglyceride and cholesterol level of 20,600 mg/dl and 1640 mg/dl, respectively. The lipid profile of the 60 patients in the protocol with this patient, the lipid profile of 64 patients on the previous high-risk ALL therapy program, and the literature were reviewed. RESULTS: Five of 60 patients on the New York-II protocol experienced transient, marked (triglyceride level > or = 1000 mg/dl), benign hyperlipidemia. No such problem was observed in the 64 patients on the New York-I protocol. Five similar cases were found in the literature during therapy with steroids (2), asparaginase (2), or both (1). There were no characteristics that distinguished these 10 patients from the vast majority of patients on similar therapy without severe hyperlipidemia. Prolonged therapy with either agent seemed to increase the possibility of hyperlipidemia. CONCLUSION: Severe hyperlipidemia during induction therapy for ALL is random, transient, and benign. Given the serious nature of the underlying disorder and the value of asparaginase and prednisone in its treatment, antileukemic therapy should not be modified when severe hyperlipidemia is observed. PMID- 7982188 TI - Decline in incidence of medulloblastoma in children. AB - BACKGROUND: Medulloblastoma is one of the most common intracranial tumors in children. The perception that the incidence of this tumor has declined is reinforced by a decline in enrollment to international trials for the disease. METHODS: A retrospective population-based study of children younger than 15 years whose brain tumors were reviewed histopathologically was performed in the county of Avon, in the southwest region of England from 1976 to 1991. Then, the incidence of medulloblastoma was studied in the noncontiguous southwest and northern regions of England, with a combined childhood population base of 20.0 million child years for the period 1976-1991. RESULTS: In Avon, 16 children with medulloblastoma presented in the period 1976-1984 and 2 in the period 1985-1991, representing a decrease in incidence from 9.6 per million per year to 1.7 per million per year. The incidence of medulloblastoma in the combined southwest and northern regions showed a significant (P = 0.006) decline from 5.5 per million per year in the period 1976-1984 to 2.8 in the period 1985-1991. Considered individually, the decline in the southwest (from 6.2 per million per year to 2.8 per million per year) was significant but that in the Northern region (from 4.7 to 2.7) was not. CONCLUSIONS: In this report, a decline in the incidence of medulloblastoma was shown. In a recent case control study, a protective effect of maternal folate, iron, and multivitamin supplementation against primitive neuroectodermal tumors, including medulloblastoma was found. The introduction of periconceptional multivitamin supplementation in the 1980s may have caused this significant decline in the incidence of medulloblastoma. PMID- 7982189 TI - Nucleolar organizer regions in lining epithelium adjacent to squamous cell carcinoma of human oral mucosa. PMID- 7982190 TI - Low grade supratentorial astrocytomas: management and prognostic factors. PMID- 7982191 TI - Preparing kids and parents for surgery. AB - Advances in medical treatment and increasing financial constraint in health care have made ambulatory surgery more prevalent in all patient populations. Pediatric surgical admissions follows this trend. The responsibility for preparing children for day surgery and caring for them at home immediately afterward rests largely with parents. Yet few parents have experience in or adequate information about this area of care. They may be as fearful as their children about the surgery and anxious about providing post-surgical care. PMID- 7982192 TI - The team approach. AB - Cardiovascular disease continues to be the major cause of death and illness in Canada. But the news is not all bad. The incidence can be reduced by minimizing one or more cardiovascular risk factors. PMID- 7982193 TI - Crime marches on. PMID- 7982194 TI - Troubled teens and substance abuse. AB - There is an increasing awareness of the existence of substance abuse problems among adolescents experiencing psychiatric difficulties. Evidence suggests that adolescents with psychiatric disorders have trouble using intoxicants safely and may experience more behavioral problems when intoxicated. PMID- 7982195 TI - Obstructive sleep apnea. AB - Humans spend one-third of their lives sleeping, yet the role of this phase of the circadian rhythm is not clear. Theories postulating the purpose of sleep include the restorative theory and the humeral theory. Both theories have identified weaknesses. What is known is that chronic disruption of sleep and/or sleep deprivation causes significant physiological and psychological symptoms. These include fatigue, lethargy and daytime somnolence accompanied by irritability, memory loss, decrease in judgment and paranoia. Obstructive sleep apnea (OSA) imposes another, more life-threatening dimension for the client. PMID- 7982196 TI - [Work in community health is about to change]. AB - Changes in Ontario's political, social and economic environments have necessitated an unprecedented transformation in the health care system. The change in focus from the individual to the community now includes core units such as families, groups and communities. Visiting nurses, public health nurses and community health nurses have worked in Community Health Centres (CHCs) since 1970. However, the role of nurses working in these centres has not been clearly defined in the literature. Nor is there is a general consensus on their title. Nurse practitioners, primary care nurses or community health nurses are all used. As well, there is no existing educational program in Ontario that trains this type of nurse. This article discusses and gives examples of nurses working in community health, whose primary clinical expertise is in using community based and community development program strategies to plan health programs. These programs are specifically developed to address the health needs of the communities they serve--in this case, Toronto's francophone community. Also demonstrated are new approaches to nursing care within a community setting. From health promotion to disease prevention, from community development to research, the practice of community health nursing is complex and exciting. PMID- 7982197 TI - [AIDS: patients' rights, professional risks, preventive measures]. AB - AIDS in the workplace poses distinct professional risks to health care providers. Identifying HIV carriers and providing specific preventive measures are not the only concerns. Societal prejudices that degenerate into attitudes and behaviors contrary to professional ethics can overwhelm nursing personnel. Their fears can lead them to make irrational decisions such as refusing to care for the client or divulging private information. The author emphasizes that nurses caring for clients with HIV or AIDS should develop a care approach based on two pivotal points. The first point is that nurses must ensure these clients receive appropriate care and that their fundamental rights are maintained. Secondly, nurses must be permitted to provide necessary care without exposing themselves to any associated health risk. The author asserts that nurses must count on complete, clear and accurate information about professional risks and preventative measures. She outlines the legal framework Canadian nurses can access and explains the legal protection available to health care providers. The development of clear and precise workplace policies based on provincial and federal laws can reduce crisis situations, workplace conflict and discrimination. PMID- 7982198 TI - Putting an end to ageism. AB - The National Advisory Council on Aging in 1991 stated a need to encourage students in the health care professions to select careers in gerontology. Indeed, it may be argued that the inclusion of a comprehensive curriculum component on aging in each nursing program is essential to address the demographic changes in Canada. With the increase in longevity it is more important than ever for nursing students to value older persons and not be fearful of interacting with this age group. This raises the question as to what nursing education has done to address this issue. PMID- 7982199 TI - Hymns of hope. PMID- 7982200 TI - Instructors, students and the law. PMID- 7982201 TI - So you want to be a nurse. PMID- 7982202 TI - Apoptosis in human tumor cells following treatment with p120 antisense oligodeoxynucleotide ISIS 3466. AB - Previously, we reported that treatment of LOX cells in vitro with phosphorothioate oligonucleotide ISIS 3466 (antisense to the human nucleolar protein p120-FB2) produced a 70% cell kill and morphological changes including nucleolar unravelling, chromatin condensation and fragmentation, and a reduction in mitotic figures consistent with apoptosis. This report shows that HeLa cells treated with ISIS 3466 also developed apoptosis: nucleosomal ladders were found when the DNA from the treated HeLa cells was extracted and run on agarose gels. The morphological changes consistent with apoptosis were found more frequently in the floating cells than in the attached cells. The percentages of floating cells and attached cells were indicators of the toxicity of the different oligonucleotides studied. Of these, oligonucleotide ISIS 3466 produced the highest percent of floating cells (78.4%). Treatment of HeLa cells with other oligonucleotides produced fewer floating cells, and the characteristic nucleosomal ladder was not found following DNA extraction. PMID- 7982203 TI - Effect of vitamin C upon gastric mucosal O6-alkyltransferase activity and on gastric vitamin C levels. AB - The repair enzyme O6-alkyltransferase will repair O6-methylguanine adducts in human DNA. In gastric mucosal DNA these adducts may be formed as a result of exposure to nitrosamines within the gastric lumen. The formation of these nitrosamines may be inhibited by vitamin C. We have examined the effect of oral vitamin C supplementation upon intragastric vitamin C levels and gastric mucosal O6-alkyltransferase levels in 48 patients. Intragastric vitamin C levels were significantly elevated in those patients with normal gastric mucosal histology after treatment, although a variable response in intragastric vitamin C to supplementation was seen in the presence of chronic atrophic gastritis. Gastric mucosal O6-alkyltransferase activities ranged from 100 to 950 fmol/mg protein before vitamin C administration. The range of enzyme activity was similar after the course of vitamin C (62-1137 fmol/mg) but O6-alkyltransferase activities were found to be higher in 33 of the 48 patients following treatment (P < 0.01). Once again this effect was more pronounced in patients with normal gastric mucosa than those displaying evidence of chronic atrophic gastritis. We speculate that inhibition of intragastric nitrosation by vitamin C results in decreased formation of O6-methylguanine-DNA. In consequence, less O6-alkyltransferase is consumed in repairing these adducts resulting in higher tissue levels of this enzyme. PMID- 7982204 TI - Detection of p53 and histopathological classification of skin tumours induced by halogen lamps in hairless mice. AB - Skin lesions induced by exposure of three strains of female hairless mice to the light emitted by uncovered halogen quartz lamps were subjected to histopathological analysis. We examined 170 representative specimens out of a total of 597 skin lesions, i.e. 38 out of 74 SKH-1 mice, 110 out of 472 MF-1 mice, and 42 out of 51 C3H mice. The results provided evidence of various types of alterations, including preneoplastic changes, such as epidermal hyperplasia, and benign tumours, such as papillomas, as well as tumours with an increasing degree of malignancy, i.e., keratoacanthoma-like tumours, appendage/basal tumours, actinic keratoses/carcinomas in situ, and squamocellular carcinomas. SKH 1 was the most sensitive strain to the far-ultraviolet wavelengths delivered by halogen lamps, as shown not only by the shortest latency time and the highest multiplicity of skin lesions but also by the highest frequency of malignant tumours. Some areas of atypical melanocyte proliferation were only detected in C3H pigmented mice. Eighty-two of the lesions excised from MF-1 mice were additionally examined for p53 protein by immunohistochemical methods. Formalin fixed, paraffin-embedded sections and frozen sections were analyzed in parallel by using polyclonal CM-1 antibody and monoclonal PAb240 antibody, respectively. A positive response for p53 was only observed in squamocellular carcinomas, and was related to the size of cancers; in fact, six out of 10 cancers of 10-30 mm in diameter were positive, whereas all 16 cancers of 2-9 mm in diameter were negative. All six positive squamocellular carcinomas were detected by using the CM-1 antibody, which recognizes both wild-type and mutant forms of p53 protein, and five of them were also positive with the PAb 240 antibody, which only recognizes the mutant form. Thus, p53 mutation appears to be a late event in the development of halogen-induced skin tumours in hairless mice, requiring a severe degree of malignancy and an advanced stage of the neoplastic mass growth. PMID- 7982205 TI - DNA replication time accounts for tumor growth variation induced by dietary fat in a breast carcinoma model. AB - Female Fischer rats were pair-fed on diets containing either safflower oil (SO) or fish oil (FO) for 6 weeks. Implanted breast 13762 MAT tumors had a doubling times of 35.4 and 55.5 h in SO and FO rats, respectively (P < 0.001). Proliferation kinetics were measured in vivo by bromedeoxyuridine (BrdUrd) labeling and bivariate DNA/BrdUrd analysis by flow cytometry. After 1 h of pulsing, the labeling index was similar in both groups. However, 6 h later, tumor cells from FO rats had significantly lower relative movement of BrdUrd-labeled cells (0.78 vs. 0.91, P < 0.001). These results reflected a significantly longer S phase duration (15.0 vs. 9.1 h, P < 0.001) in FO rats and accounted for all the difference in tumor growth rates. This mechanism, which has not previously been reported, implies a significant role for fatty acids in DNA replication. PMID- 7982206 TI - Endogenous formation of N-nitrosoproline and other N-nitrosamino acids in tobacco users. AB - The endogenous formation of N-nitroso compounds in tobacco users, namely chewers of tobacco + lime, betel quid with tobacco, and without tobacco, was determined by N-nitrosoproline test. Twenty-four- or six-hour urine samples were collected from volunteers for 3 days: day 1 without proline, day 2 after ingesting 100 mg proline three times a day and day 3 after ingesting 100 mg proline together with 100 mg ascorbic acid three times a day. The urine samples were analysed for the following N-nitrosamino acids: N-nitrosoproline, N-nitrososarcosine, N nitrosopropionic acid, N-nitrosobutyric acid, N-nitrosothiozolidine-4-carboxylic acid, and N-methyl nitrosothiozolidine-4-carboxylic acid using gas chromatography thermal energy analyser. It was observed that chewers of tobacco + lime excreted high basal levels of N-nitrosoproline on day 1 as compared with betel quid chewers with tobacco and without tobacco and those in the 'no habit' group. Levels of N-nitrosoproline on day 2 were 15.14 +/- 4.51 microns/mole creatinine in the tobacco + lime group, 3.55 +/- 1.22 microns/mole creatinine in the betel quid tobacco group, 4.72 +/- 1.35 microns/mole creatinine in the betel quid group while levels were 3.34 +/- 0.83 microns/mole creatinine in the 'no habit' group. A decrease in the N-nitrosoproline levels was observed in all the four groups on ingestion of ascorbic acid. This preliminary study suggests that there is a statistically significant increase in endogenous nitrosation in tobacco + lime chewers as compared with those with no habit, and ascorbic acid has an anti nitrosating action in vivo. PMID- 7982207 TI - Piperine, a major ingredient of black and long peppers, protects against AFB1 induced cytotoxicity and micronuclei formation in H4IIEC3 rat hepatoma cells. AB - We studied the effect of piperine on the cytotoxicity and genotoxicity of aflatoxin B1 (AFB1) in rat hepatoma cells H4IIEC3/G-(H4IIE) using cellular growth and formation of micronuclei as endpoints. Piperine was earlier shown to inhibit cytochrome P-450-dependent aryl hydrocarbon hydroxylase and 7-methoxycoumarin demethylase activities in preparations of these cells with 1/2 maximum inhibition at 30-50 microM (Singh J. and Reen R.K., Current Science, 66, 365-369, 1994). The results of the present study showed that AFB1 inhibited the growth of H4IIE cells with an ED50 of 15 nM. Piperine markedly reduced the toxicity of the mycotoxin. Thus at 100 microM piperine largely restored the rate of growth of the cells. Likewise, piperine reduced the AFB1-induced formation of micronuclei in a concentration-dependent manner. Piperine itself was not toxic to the cells up to a concentration of almost 100 microM. The results suggest, that piperine is capable of counteracting AFB1 toxicity by suppressing cytochromes P-450 mediated bioactivation of the mycotoxin. PMID- 7982208 TI - Identification and partial characterization of the c-jun oncogene in Xenopus laevis. AB - Sequencing analysis of a 275-nt cDNA fragment encoding the DNA-binding region at the carboxyl terminal of the Xenopus c-jun protein product shows that this region exhibits 77-79% nucleotide homology and 93% amino acid homology with the DNA binding region of mouse and human c-jun, and contains an intact leucine zipper motif and a basic DNA-binding region. Xenopus c-jun mRNA is induced in quiescent Xenopus A6 kidney cells by 12-O-tetradecanoylphorbol-13-acetate, PDGF and cycloheximide. This 'immediate early' response suggests that Xenopus c-jun may be similar in both structure and function to that observed for its mammalian counterpart. PMID- 7982209 TI - Retardation of benzo[a]pyrene-induced epidermal tumor formation by the potent antioxidant 4b,5,9b,10-tetrahydroindeno[1,2-b]indole. AB - The ability of the potent antioxidant, 4b,5,9b,10-tetrahydroindeno[1,2-b]indole (THII), to inhibit tumor formation by topically-applied benzo[a]pyrene was evaluated using a complete carcinogenicity mouse skin bioassay. THII was administered by direct application to the skin, in the food or through the drinking water. In each case, THII increased the average time until the appearance of tumors by 4 weeks, and also decreased the total number of tumors compared with benzo[a]pyrene alone. These protective effects corresponded with the ability of THII to inhibit benzo[a]pyrene- or 12-O-tetradecanoylphorbol-13 acetate-induced epidermal ornithine decarboxylase activity, a biomarker of tissue proliferation in skin of the treated animals. This is the first report of an antioxidant administered in food or water inhibiting chemically induced skin carcinogenesis. PMID- 7982210 TI - Elevated levels of MDM-2 and p53 expression are associated with high grade non Hodgkin's lymphomas. AB - The role of p53 in the evolution of non-Hodgkin's lymphomas (NHL) is unclear. Mutations of the p53 gene appear to be relatively uncommon but stabilized p53 protein, as detected by immunohistochemistry, has indicated a more frequent involvement of p53. As dysfunction of p53 protein has also been suggested to occur after overexpression of the mdm-2 protein, we have therefore investigated a series of non-malignant hyperplastic reactive lymphoid tissues and NHL to examine whether the levels of expression of MDM-2 correlated to positivity of p53 protein staining. Northern blot analysis of MDM-2 expression was compared to glucose-6 phosphate dehydrogenase (G6PD) expression by densitometry to quantify the relative levels of MDM-2 expression. Consistent low levels of MDM-2 expression were observed in non-malignant lymphoid tissue and in low grade NHL, however, 13/15 high grade NHL exhibited a 2-15-fold increase in MDM-2 expression. Interestingly similar elevations in p53 mRNA expression were also observed in 6/15 high grade NHL. Positive staining of the p53 protein did not, however, correlate with elevated mRNA levels of either MDM-2 or p53. The significance of these observations is discussed. PMID- 7982211 TI - Induction of mammary tumors in rat by intraperitoneal injection of NMU: histopathology and estral cycle influence. AB - In order to obtain an experimental model we induced mammary tumors in female Sprague-Dawley rats. The carcinogen N-nitroso-N-methylurea (NMU) was injected intraperitoneally (i.p.) at doses of 50 mg/kg body weight when animals were 50, 80 and 110 days old. Tumor sizes were measured with a caliper and their growth parameters and histopathological properties were tested. For 100 rats, 88.4% of developed lesions were ductal carcinomas, histologically classified as 52.8% cribiform variety, 30.6% solid carcinoma. Metastases in liver, spleen and lung were present. Other primary tumors were detected with low incidence. The influence of the rat estrous cycle during the first exposure to intraperitoneal NMU injection was studied. The latency period in estrus, proestrus and diestrus was 82 +/- 15, 77 +/- 18 and 79 +/- 18 days, respectively. Tumor incidence was significantly higher in estrus (95.2%) than proestrus (71.4%) or diestrus (77.4), (P < 0.01). Mean number or tumors per animal was similar among the three groups (4.4 +/- 3.2, 3.8 +/- 3.6, 3.2 +/- 1.8). The procedure described appears to be the simplest method for inducing experimental mammary tumors in rats. PMID- 7982212 TI - Dose-dependent inhibition of glutathione S-transferase placental form-positive hepatocellular foci induction in the rat by methyl propyl disulfide and propylene sulfide from garlic and onions. AB - Two organosulfur compounds, methyl propyl disulfide (MPD) and propylene sulfide (PS) from garlic and onions, were studied for their modifying effects on hepatocarcinogenesis in the F344 rats. Modifying potential was scored by comparing the number and area per cm2 of induced glutathione S-transferase placental form (GST-P)-positive foci in the liver. MPD and PS significantly reduced both these parameters of GST-P-positive foci in a dose-dependent manner. To investigate possible mechanisms of inhibition, ornithine decarboxylase (ODC) and spermidine/spermine N1-acetyltransferase (SAT) activities were measured. In MPD and PS-high dose-treated liver tissue there was a tendency for their decrease, albeit non-significant, which suggested that the inhibitory effect might have been caused by decreased cell proliferation associated with decreased polyamine biosynthesis. In evaluating relationships between diet and cancer, it is thus necessary to consider various effects in assessing possible protective roles of garlic and onions. PMID- 7982214 TI - Studies of the neutral trisaccharides of goat (Capra hircus) colostrum and of the one- and two-dimensional 1H and 13C NMR spectra of 6'-N acetylglucosaminyllactose. AB - Four neutral trisaccharides were isolated from goat colostrum by dialysis, and ion-exchange, activated charcoal column, preparative paper, and Bio-Gel P-4 column chromatography. The following structures were elucidated by GC analysis of hydrolysis products and by 400-MHz 1H NMR spectroscopy: alpha-L-Fuc p-(1-->2) beta-D-Gal p-(1-->4)-D-Glc, alpha-D-Gal p- (1-->3)-beta-D-Gal p-(1-->4)-D-Glc, beta-D-Gal p-(1-->3)-beta-D-Gal p-(1-->4)-D-Glc, and beta-D-Gal p-(1-->6)-beta-D Gal p-(1-->4)-D-Glc. beta-D-Glc pNAc-(1-->6)-beta-D-Gal p-(1-->4)-D-Glc, previously reported to be present in goat milk, was not detected in this study. beta-D-Glc pNAc-(1-->6)-beta-D-Gal p-(1-->4)-D-Glc (6'-N- acetylglucosaminyllactose) was prepared by beta-D-galactosidase digestion of beta D-Gal p-(1-->3)[beta-D-Glc pNAc-(1-->6)]-beta-D-Gal p-(1-->4)-D-Glc (lacto-N novotetraose) and characterized by one- and two-dimensional NMR spectroscopy at 600 MHz. PMID- 7982215 TI - Synthesis of the 5-aminopentyl glycoside of beta-D-Gal p-(1-->4)-beta-D-Glc p NAc (1-->3)-L-Fuc p and fragments thereof related to glycopeptides of human Christmas factor and the marine sponge Microciona prolifera. AB - The marine sponge Microciona prolifera and human coagulation factor IX (Christmas factor)-related mono- to tri-saccharide 5-aminopentyl glycosides beta-D-Gal p-R (5), beta-D-Glc pNAc-R (16), beta-D-Gal p-(1-->4)-beta-D-Glc p NAc-R (26), beta-D Glc p NAc-(1-->3)-beta-L-Fuc p-R (39), beta-D-Glc pNAc-(1-->3)-alpha-L-Fuc p-R (43), beta-D-Gal p-(1-->4)-beta-D- Glc pNAc-(1-->3)-beta-L-Fuc p-R (45), and beta D-Gal p-(1-->4)-beta-D-Glc p NAc-(1-->3)-alpha-L-Fuc p-R (47), where R is a 5 aminopentyloxy spacer moiety, which allowed the construction of glycoconjugates, were prepared. Thus, 3,4,6-tri-O-acetyl-2-deoxy-2-(2,2,2- trichloroethoxycarbonyl amino)-alpha-D-glucopyranosyl trichloroacetimidate (10) and 1,3,4,6-tetra-O acetyl-2-chloro-acetamido-2- deoxy-beta-D-glucopyranose (13) were condensed with N-Z-protected 5-amino-pentanol (2) followed by conversion of the coupling products into the corresponding N-acetylglucosamine derivatives, to give compound 16 after deblocking. Similarly, the donors 10 and 13 were coupled to position 3 of suitably protected aminopentyl beta- (32) and alpha- (37) -L-fucopyranosides, to give the disaccharides 39 and 43, respectively. Starting from lactose, O (2,3,4,6-tetra-O-benzoyl-beta-D-galactopyranosyl)-(1-->4)-3,6-di-O- benzoyl-2 deoxy-2-(2,2,2-trichloroethoxycarbonylamino)-alpha-D-glu copyranosyl trichloroacetimidate (23) was prepared and used as an efficient disaccharide donor for the construction of ligand 26 from 2 and of the trisaccharide ligands 45 and 47 from fucosides 32 and 37, respectively. PMID- 7982216 TI - The reaction between epichlorohydrin and polysaccharides: Part 1. Syntheses of some model substances with non-cyclic substituents. AB - Five derivatives of methyl alpha-D-glucopyranoside, in which the substituents form noncyclic structures, have been prepared as model substances for possible structural elements formed on reaction of polysaccharides with epichlorohydrin. The substances were converted into the permethylated alditol-1-d derivatives and characterised by CIMS and EIMS. PMID- 7982217 TI - Alpha-(1-->2)-, and alpha-(1-->3)-, and alpha-(1-->6)-linked thioglycosidic disaccharides: syntheses and anti-HIV testing of thiokojibiose octaacetate, thionigerose, and thioisomaltose. AB - The syntheses of several alpha-linked thioglycosidic disaccharides are described, including thiokojibiose octaacetate (1), thionigerose (2), and thioisomaltose (3). The title compounds were synthesized by coupling 2,3,4,6-tetra-O-acetyl-1.5 acetyl-1-thio-alpha-D-glucopyranose (4) with either 1,3,4,6-tetra-O-acetyl-2-O trifluoromethylsulfonyl-beta-D-manno pyr anose (7), 1,2:5,6-di-O-isopropylidene-3 O-trifluoromethylsulfonyl-alpha-D-++ +allofuranose (15), or methyl 2,3,4-tri-O acetyl-6-deoxy-6-iodo-alpha-D-glucopyranoside (17), respectively. Thiokojibiose octaacetate in turn was converted to 3,4,6-tri-O-acetyl-2-S-(2,3,4,6-tetra-O acetyl-alpha-D-glucopyranosyl)-2 -thio-alpha-D-glucopyranosyl bromide (9), which was used to obtain several related disaccharides and one trisaccharide. All of the compounds, including thiomaltose and thiotrehalose, which were resynthesized by known methods, were tested for their anti-HIV activity in either CEM or MT-2 cells. Anti-HIV activity was noted only with thiokojibiose octaacetate and its 1 thio analogue (14), which had IC50 values of 51 and 48 micrograms/mL in CEM cells, respectively. PMID- 7982218 TI - The preparation and characterization of some Amadori compounds (1-amino-1-deoxy-D fructose derivatives) derived from a series of aliphatic omega-amino acids. AB - Amadori compounds (1-amino-1-deoxy-D-fructose derivatives) were prepared by reacting D-glucose with a series of aliphatic amino acids. These include Amadori compounds derived from glycine (1), beta-alanine (2), gamma-amino butyric acid (3), delta-aminovaleric acid (4), epsilon-amino-caproic acid (5) and N alpha formyl-L-lysine (6). In the FAB mass spectra, molecular-ion clusters as well as fragment ions corresponding to loss of water or CO2 molecules were observed. The 13C NMR spectra indicate that all the compounds are conformationally unstable, but that the predominant form present in solution (D2O) is the beta-pyranose form. The 1H NMR spectra of 1 and 2 indicate a slow rotation around the C-1-C-2 bond, possibly as a result of an intramolecular hydrogen bond involving the carboxyl group. The pK alpha's of all compounds were measured by pH potentiometric titration in 0.2 M KNO3 solution at 25 degrees C. All compounds showed a decrease in the basicity of their amino groups (in the order of approximately 1.5 of the K alpha value), and 1 and 2 showed a decrease in the basicity of their carboxyl groups (in the order of approximately 0.2) in comparison with that of parent amino acids. PMID- 7982219 TI - Selective pivaloylation and diphenylacetylation of cyclomalto-oligosaccharides. AB - Regioselective acylation of cyclomalto-oligosaccharides was achieved using pivaloyl and diphenylacetyl chlorides. The reaction of cyclomaltohexaose (1) with pivaloyl chloride gave the hexakis(2,6-di-O-pivaloyl) derivative 19 in 66% yield. Similar reaction with cyclomalto-heptaose (2) led to the octakis(2I,6I,6II,6III,6IV,6V,6VI ,6VII-O-pivaloyl) 26 and the 17 heptakis(6-O pivaloyl) derivatives in 34 and 26% yields, respectively. The octakis(6-O pivaloyl) derivative 18 was the only compound isolated (72%) in the reaction of pivaloyl chloride with cyclomalto-octaose (3). Diphenylacetylation of 1-3 gave the symmetrical (20-22) and the non-symmetrical (27-29) per(6-O-diphenylacetyl) esters as major and minor products, respectively. PMID- 7982220 TI - Synthesis of a di-O-methylated pentasaccharide for use in the assay of N acetylglucosaminyltransferase III activity. AB - The biantennary oligosaccharide analogue beta-D-Glc pNAc-(1-->2)-alpha-D-Man p-(1 ->3)-[beta-D-Glc pNAc-(1-->2)-alpha- D-Man p-(1-->6)]-beta-D-man p-O(CH2)8COOMe (3) is a potential substrate for N-acetylglucosaminyltransferases (GlcNAcTs) III V which are present in mammalian cells. The di-O-methylated analogue of 3, beta-D Glc pNAc-(1-->2)-[4-O-methyl-alpha-D-Man p]-(1-->3)-[beta-D-Glc pNAc-(1-->2)-[6-O methyl-alpha-D-Man p]-(1-->6)]-beta-D-Man p-O-(CH2)8COOMe (5), was prepared by a block synthesis approach involving sequential addition of two O-methylated disaccharide donors to a protected central beta-D-Man residue. The OH groups acted on by GlcNAcT-IV and -V are protected from glycosylation in 5 since they are present as their methyl ethers. Pentasaccharide 5 was found to be an excellent substrate for GlcNAcT-III (EC 2.4.1.144) from rat kidney with Km = 0.15 mM. The product formed by incubation of 5 with a rat kidney extract, in the presence of UDP-GlcNAc, was isolated, structurally characterized by NMR spectroscopy and confirmed to be the expected di-O-methyl hexasaccharide where a beta-D-Glc pNAc residue had been added to OH-4 of the central beta-D-Man p unit. PMID- 7982221 TI - Synthesis of transition-state analogues as potential inhibitors of sialidase from Influenza virus. AB - Sodium 5-acetamido-2,6-anhydro-3,4,5-trideoxy-D-manno-non-2-enonate (2) has been synthesized from N-acetyl-4-deoxy-neuraminic acid methyl ester (4). Sodium 2,6 anhydro-3-deoxy-L-arabino-hept-2-enonate (3), 4-acetamido-2,6-anhydro-3,4-dideoxy L-arabino-hept-2-enonic acid (18e), and 4-acetamido-2,6-anhydro-3,4-dideoxy-L ribo-hept-2-enonic acid (18a) have been prepared from L-arabinose. The above compounds were investigated as inhibitors of sialidase from Influenza virus. Only compound 2 showed a significant inhibitory activity (Ki 8 x 10(-2) mM) against the enzyme. PMID- 7982222 TI - Structural investigation of the capsular polysaccharide of Escherichia coli O101 : K103 : H- using bacteriophage degradation and NMR spectroscopy. AB - NMR spectroscopy was performed on the depyruvated capsular antigen of E. coli K103 and on the oligosaccharide obtained by depolymerisation of the native polysaccharide with a viral-borne endoglycanase. This capsular polysaccharide is the only one to be co-expressed with O group 101 and joins a small group of unusual capsular polysaccharides which possess pyruvic acid as the only acidic function. The primary structure was shown to be composed of the repeating unit: [formula: see text] PMID- 7982223 TI - Structural elucidation of the capsular polysaccharide produced by Escherichia coli O20 : K84 : H26. AB - The primary structure of the acidic capsular antigen produced by E. coli K84 was shown by glycose and methylation analysis, and by 1D and 2D 1H and 13C NMR studies of the polysaccharide and an oligosaccharide produced by lithium ethylenediamine degradation of the polysaccharide, to be comprised of linear hexasaccharide repeating units of the following structure: -->4)alpha-D-GaI pA-(1 ->3)-alpha-D-Man p-(1-->4)-beta-D-GIc p-(1-->3)-alpha- D-Glc pNAc-(1-->2)-beta-D Man p-(1-->3)-beta-D-Man pNAc-(1-->. PMID- 7982224 TI - Synthesis of 2-deoxy-alpha-D-arabino-hexopyranosyl phosphate and 2-deoxy maltooligosaccharides with phosphorylase. AB - A convenient one-step synthesis of 2-deoxy-alpha-D-arabino-hexopyranosyl phosphate on a millimolar scale is described by reaction of potato phosphorylase with D-glucal at equimolar phosphate concentration. Furthermore, in the presence of catalytic amounts of phosphate, a 2-deoxy-maltooligosaccharide is obtained from maltotetraose and D-glucal. The water-insoluble oligosaccharide was isolated and characterized by 1H and 13C NMR spectroscopy. An average dp of 20 was thus determined. PMID- 7982225 TI - Composition of the coagulant polysaccharide fraction from Strychnos potatorum seeds. AB - The composition of the coagulant polysaccharide fraction from Strychnos potatorum seeds is described. This fraction comprises a 1:1.7 mixture of a galactomannan and a galactan. The structure of these polysaccharides is also discussed. In addition, the coagulant properties of the polysaccharide fractions of two other Strychnos species, innocua and nux-vomica, have been assayed. PMID- 7982226 TI - An antitumor, branched (1-->3)-beta-D-glucan from a water extract of fruiting bodies of Cryptoporus volvatus. AB - A water-soluble, (1-->6)-branched (1-->3)-beta-D-glucan (H-3-B) was isolated from a hot-water extract of the fruiting bodies of the fungus, Cryptoporus volvatus (Basidiomycetes). Enzymatic analysis using exo-(1-->3)-beta-D-glucanase and methylation analysis indicated that this polysaccharide has a main chain composed of beta-(1-->3)-linked D-glucopyranosyl residues, and single, beta-(1-->6)-linked D-glucopyranosyl residues attached as side chains to, on average, every fourth sugar residue of the main chain. This structure was confirmed by 13C NMR spectra of the glucan in Me2SO-d6. The weight-average molecular weight (Mw) of H-3-B was determined to be 44.0 x 10(4) by gel permeation chromatography equipped with a low-angle laser-light-scattering photometer. The electron microscopic observations showed that H-3-B and its sonicated sample (S-H-3-B, Mw = 13.7 x 10(4)) can be described as linear worm-like chains. The mass per unit length for native and sonicated H-3-B was determined to be 1750 and 1780 g mol-1 nm-1, respectively, from the contour lengths obtained by electron microscopy and the molecular weights. These values are in good agreement with that expected for the triple stranded structure. A sample denatured in 0.1 M NaOH and subsequently renatured by neutralization showed a mixture of linear and cyclic structures, and larger aggregates with less well-defined morphology. The H-3-B and S-H-3-B had antitumor activity against the Sarcoma 180 tumor. PMID- 7982227 TI - The unusually stable crystal structure of neo-inositol. PMID- 7982228 TI - Inhibition of bacterial and viral sialidases by 3-fluoro-N-acetylneuraminic acid. PMID- 7982229 TI - Crystal and molecular structure of allyl O-(sodium 3-deoxy-alpha-D-manno-2 octulopyranosylonate)-(2-->8)-O-(sodium 3-deoxy-alpha-D-manno-2 octulopyranosidonate)-monohydrate. AB - The alpha-(2-->8)-linked Kdo disaccharide derivative allyl O-(sodium 3-deoxy alpha-D-manno-2-octulopyranosylonate)-(2-->8)-O-(sodium 3-deoxy-alpha-D-manno-2 octulopyranosidonate)-monohydrate C19H28O15Na2.H2O, M(r) = 542.32, is orthorhombic, P2(1)2(1)2(1) with a = 9.229(1), b = 12.036(1), c = 21.671(1) A, and Z = 4. The structure was solved by direct methods and refined to R = 0.040 for 2677 observed reflections. The torsion angles about the (2-->8)-glycosidic bond are stabilized by an intramolecular hydrogen bond between the carboxylate group at the anomeric carbon atom of the terminal Kdo residue and the hydroxyl group O-17 of the second Kdo moiety. PMID- 7982230 TI - Synthesis of 4,6:2',3':4',6'-tri-O-cyclohexylidene-alpha,alpha'-trehalose 2 palmitate: an intermediate for the synthesis of mycobacterial 2,3-di-O-acyl alpha,alpha'-trehalose antigens. AB - The aim was to 'triprotect' trehalose by placing various acetals, or related protecting groups, across the 4,6-, 2',3'-, and 4',6'-positions, leaving the 2,3 positions free for subsequent acylation. Isopropylidene and ethylidene acetals were studied, with the formation of a small amount of 4,6:2',3':4',6'-tri-O isopropylidene-alpha,alpha'-trehalose. 4,6:4',6'-Di-O-benzylidene-2',3'-O (tetraphenyldisiloxane-1,3-d iyl)-alpha, alpha'-trehalose 2,3-diacetate was prepared in low yield. 1,1-Dimethoxycyclohexane reacted with methyl alpha-D glucopyranoside to afford the 4,6-O-cyclohexylidene derivative, isolated as the diacetate; mild acid cleavage of the acetal gave the 2,3-diacetate. 4,6:2',3':4',6'-Tri-O-cyclohexylidene-alpha,alpha'-trehalose is the major product of the reaction between alpha,alpha'-trehalose and 1,1-dimethoxycyclohexane. 2,3:4,6:2',3':4',6'-Tetra-O-cyclohexylidene-, 4,6:4',6'-di-O-cyclohexylidene-, and 4,6-O-cyclohexylidene-alpha,alpha'-trehaloses were also isolated in lower yields, all acetals being characterised as their peracetates. The proportions of the different trehalose acetals were dependent upon the molar ratio of 1,1 dimethoxycyclohexane and particularly on the reaction temperature. The triprotected trehalose acetal was acylated with palmitic acid, with excellent regioselectivity, affording the 2-O-palmitoyl ester. This 2-monoacylated, triprotected trehalose is a key intermediate for the synthesis of 2,3-di-O-acyl alpha,alpha'-trehalose glycolipid antigens, isolated from Mycobacterium fortuitum and Mycobacterium tuberculosis. PMID- 7982231 TI - Synthesis of alpha-D-galactopyranosyl-linked oligosaccharides containing the alpha-Gal-->beta-Gal-->GlcNAc sequence employing methyl-2,3,4,6-tetra-O-(4 methoxybenzyl)-1-thio-beta-D-galactopyranosid e as an efficient glycosyl donor. AB - Synthesis of two trisaccharides and a tetrasaccharide, namely, alpha-Gal-(1-->3) beta-Gal-(1-->3)-GlcNAc-beta-OBn (6), alpha-Gal-(1-->3)-beta-Gal-(1-->4)-GlcNAc beta-OBn (9) and alpha-Gal-(1-->3)-beta-Gal-(1-->4)-GlcNAc-beta-(1-->6)-GalNAc- alpha-OBn (19) was accomplished through development and utilization of a key alpha-galactosyl donor, methyl 2,3,4,6-tetra-O-(4- methoxybenzyl)-1-thio-beta-D galactopyranoside (1). PMID- 7982232 TI - Structure elucidation of an acetylated saponin of Blighia welwitschii by NMR spectroscopy. AB - A new glycosylated triterpene has been isolated from the fruit of Blighia welwitschii. The structural analysis of its peracetylated derivative (1) was performed by 2D homonuclear and heteronuclear NMR spectroscopy. The saponin was shown to contain hederagenin and five sugar residues forming two glycosyl chains. The complete structure of the saponin was established to be 3-O-[beta-D-Glc p-(1- >3)-alpha-L-Rha p-(1-->2)-alpha- L-Ara p]-28-O-[beta-D-Glc p-(1-->6)-beta-D-Glc p]hederagenin. PMID- 7982233 TI - Characterisation of an anti-ulcer pectic polysaccharide from leaves of Panax ginseng C.A. Meyer. AB - Structural characterisation of an anti-ulcer polysaccharide (GL-BIII), purified from leaves of Panax ginseng C.A. Meyer, was studied. Methylation analysis indicated that GL-BIII consisted mainly of terminal Arap, 4- or 5-substituted Ara, 2,4-disubstituted Rha, 4- and 6-substituted Gal, and 3,6-disubstituted Gal. Single radial gel diffusion using beta-glucosyl-Yariv antigen indicated that GL BIII contained a small proportion of a beta-(1-->3,6)-galactan moiety. GL-BIII also contained terminal, 4-substituted, and 3,4-disubstituted GalA, and terminal and 4-substituted GlcA. Base-catalysed beta-elimination suggested that some 2 substituted Rha in GL-BIII was attached to position 4 of a 4-substituted uronic acid. Both mild acid hydrolysis and endo-alpha-(1-->4)-polygalacturonase digestion of GL-BIII did not give fragments consisting mainly of GalA. Methylation analysis and GC-MS analysis of acidic oligosaccharides liberated by partial acid hydrolysis indicated that GL-BIII contained a GalA-(1-->4)-Rha unit in addition to longer acidic units consisting of 2-substituted Rha and 4 substituted GalA. Lithium-mediated degradation of GL-BIII followed by borohydride reduction gave small amounts of fractions containing long and intermediate neutral oligosaccharide-alditols and a large amount of a fraction containing short oligosaccharide-alditols. The long neutral oligosaccharide-alditol fraction mainly comprised 4- or 5-substituted Ara, terminal Galf, 6-substituted Glc, and 2 substituted Man, whereas the intermediate oligosaccharide-alditol fraction consisted mainly of terminal and 6-substituted Galp, 6-substituted Glc, and 2 substituted Man. Methylation analysis and GC-MS analysis of the short oligosaccharide-alditol fraction suggested that it contained at least 14 kinds of di- to tetra-saccharide-alditols such as Gal-(1-->2)-Rha-ol, Gal-(1-->4)-Rha-ol, Ara-->Ara-ol, and Ara-->Ara-->Ara-ol. PMID- 7982234 TI - Depressed immunity and the development of cancer. AB - Various disorders of immune competence are associated with increases in uncommon tumors, particularly non-Hodgkin's lymphomas (NHLs), which often exhibit unusual features: they are frequently extranodal, show a broad spectrum of lesions, ranging from benign polyclonal hyperplasia to frankly malignant monoclonal lymphomas, and are frequently localized to the brain. Of 7136 tumors in organ transplant recipients, the predominant lesions are NHLs, carcinomas of the skin and lips, carcinomas of the vulva/perineum, Kaposi's sarcoma (KS), and renal carcinomas. Skin cancers present unusual features: predominance of squamous cell carcinomas, young age of the patients, and a high incidence of multiple tumors. Cancers of the vulva/perineum occur at a much younger age than in the general population. In AIDS patients the most common malignancy is KS, which occurs in 14%, whereas NHLs afflict 2.9%. A variety of other tumors occur in these patients. The most common tumors in patients with primary immunodeficiency states are NHLs (49%), leukemias (13%), various carcinomas (9%), and Hodgkin's disease (7%). PMID- 7982235 TI - Glutathione S-transferase Mu phenotype in patients with familial adenomatous polyposis and in unaffected controls. AB - Patients with familial adenomatous polyposis (FAP) are at high risk for duodenal tumors, the distribution of which suggests that bile is important in their development. Studies of the bile of FAP patients suggest that it contains an excess of active carcinogens. Defective hepatic metabolism of carcinogens might account for these findings. The isozyme glutathione S-transferase mu (GST-mu) plays a major role in the hepatic metabolism of carcinogens. Peripheral blood GST mu status reflects hepatic GST-mu status. The concentration of GST-mu was therefore measured by enzyme-linked immunosorbent assay of heparinized peripheral blood samples taken from 31 unrelated patients with FAP and from 38 unrelated control patients. FAP and control patients were matched for age, sex, diet, and smoking status. The median GST-mu concentration (micrograms per milliliter) was 0.5 (interquartile range, 0 to 11.6) in the FAP group and 8.85 (0.9 to 29.4, p = 0.0013) in the control group. Of the 31 FAP patients, ten had no detectable GST mu activity compared with only one of the 38 controls (p = 0.002), while 71% of FAP patients had GST-mu concentrations less than a supplied positive control, compared with 50% of control patients (p = 0.064). Abnormal hepatic metabolism of carcinogens by GST-mu might contribute to the development of intestinal tumors in patients with FAP. PMID- 7982236 TI - Determination of lignans and isoflavonoids in plasma by isotope dilution gas chromatography-mass spectrometry. AB - A quantitative method based on ion-exchange chromatography and isotope dilution gas chromatography-mass spectrometry using deuterated internal standards for the determination of plasma lignans and isoflavonoid phytoestrogens has been developed. These compounds are potential anticancer compounds originating from the diet. The method allows the assay of seven different compounds, while unconjugated (free) and sulfated compounds are determined separately from glucuronides and sulfoglucuronides. Results of plasma analyses in Finnish women and in Japanese men are presented. Total concentrations of individual compounds vary greatly between the subjects (from pmol/l to mumol/l), with the Finnish vegetarians and Japanese subjects having higher values. The Finns have relatively high lignan and the Japanese very high isoflavonoid values. It is concluded that the new method allows the determination of the whole plasma lignan and isoflavonoid phytoestrogen profile. PMID- 7982237 TI - Oncogene activation: an informative marker for the human papillomavirus-lesions severity. AB - The aim of this study was the detection of c-Ha-ras and c-myc activation and p21ras and p62myc expression in anogenital HPV-associated lesions. Thirty-two women with cervical and vaginal lesions and forty men with anal or penile warts were enrolled for the study. Biopsies were subjected to histological assessment, in situ hybridization with biotinylated probes, and immunohistochemistry. In both women and men, most of the biopsies showing no major histological abnormalities were negative for HPV detection. The low-grade squamous intraepithel-)ial lesions (SIL) harbored HPV in more than 50% of cases. The high-grade SIL contained mostly oncogenic HPV. C-Ha-ras and c-myc activation was detected in 31/41 HPV-positive lesions, especially in lesions harboring HPV 31/35/51 or multiple HPV. Simultaneous activated oncogenes were found in 7 out of 9 high-grade SIL and in 21 out of 45 low-grade SIL. In most of the lesions, we demonstrated concurrent detection of p21ras and p62myc proteins and oncogene activation. Our study shows that c-Ha-ras and c-myc activation is correlated with oncoprotein expression and associated with the presence of oncogenic HPV. Such activation might play a role in the development of high-grade anogenital dysplasia. PMID- 7982238 TI - Prognostic prediction in neuroblastomas: clinical significance of combined analysis for Ha-ras p21 expression and N-myc gene amplification. AB - Ha-ras p21 expression and N-myc gene amplification were examined in 69 neuroblastomas and their clinical significance was analyzed retrospectively. Thirty-nine (89%) of forty-four patients who survived for more than 2 years after diagnosis showed high Ha-ras p21 expression, whereas 19 (76%) of 25 patients who died of progressive disease showed low Ha-ras p21 expression in their tumors. Although all 14 patients whose tumors exhibited N-myc gene amplification died of the disease, 11 other patients (56%) who died did not exhibit N-myc gene amplification. When we considered both low Ha-ras p21 expression and N-myc gene amplification as risk factors, 23 (92%) of the 25 patients who died had at least one of the two and thus could have been predicted to be high-risk patients at diagnosis. The combined analysis of the two factors should provide more accurate information pertinent to patient care. PMID- 7982239 TI - New serum markers for small-cell lung cancer. II. The neural cell adhesion molecule, NCAM. AB - The neural cell adhesion molecule (NCAM) was recently suggested as a marker for small-cell lung cancer (SCLC). Immunohistochemical analysis demonstrated the presence of the NCAM in 78% of SCLC patients and in 25% of patients with other cancer forms. NCAM was proposed to be the most sensitive marker for SCLC, and it may also be an important prognostic marker for SCLC. We used a competitive ELISA to analyze the concentrations of NCAM in sera from 96 SCLC patients, 16 patients with non-SCLC, 4 patients with other cancer forms, and 16 healthy controls. All sera were collected at the time of diagnosis, before the patients received chemotherapy. The polyclonal antibody used in the assay recognized all three isoforms of NCAM. The concentration of NCAM was related to clinical parameters of the patients such as age, sex, blood group status, stage of disease, organ site involvement of metastases, survival, and expression of the ganglioside fucosyl GM1 (FucGM1). Sera were considered positive if NCAM concentrations were higher than the mean concentration of healthy controls plus two standard deviations. Twenty-two percent of the sera from SCLC patients were positive for NCAM. No difference in concentration was found between SCLC patients with localized and extensive disease. Serum from one patient with cancer of the thyroid, but no sera from non-SCLC patients or normal healthy controls, was positive. The expression of NCAM did not correlate to any of the clinical parameters, and no correlation was found to the other serum marker, FucGM1.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7982240 TI - Mammography screening controversies. AB - Some organizations in the U.S. recommend mammography screening at 1- to 2-year intervals for those aged 40 to 49 and annually from the age of 50. In Canada and Europe, screening mammography is not recommended for women aged 40 to 49, and mammography every 2 to 3 years for women aged 50 to 69. The screening studies in Europe show no evidence of effectiveness of mammography screening in women aged 40 to 49 in the first 8 to 10 years after initiation of screening. Although at 12 years the recent Swedish overview analysis shows a 13% reduction, this is nonsignificant and the confidence intervals are wide. In the National Breast Screening Study (NBSS) in Canada, annual two-view mammography and physical examinations by carefully trained health professionals were given. In women aged 40 to 49 the ratio of proportions of deaths was 1.36 (95% CI 0.84, 2.21). For women aged 50 to 59, the NBSS evaluated the contribution of mammography over and above physical examination. In spite of detecting many more cancers, mammography did not result in a reduction in breast cancer mortality at 7 years (OR 0.97; 95% CI 0.62, 1.52). Although these results suggest the benefit from screening may be less than assumed, for women over 50, biennial screening to age 74 is probably appropriate in population programs, although careful monitoring will be necessary to ensure that the anticipated effect is achieved. PMID- 7982241 TI - Effect of tamoxifen on mammary preneoplasia: relevance to chemopreventive intervention. AB - The nonsteroidal antiestrogen tamoxifen (TAM) is used to treat receptor-positive breast cancer and is now being evaluated for prophylaxis of "high-risk" population. The present study seeks to examine mechanisms that may be critical for prophylactic effects of TAM on transformation-sensitive mammary tissue. The experimental systems utilized included: in vivo rodent models for mammary tumorigenesis and in vitro cell culture models for preneoplastic transformation. In the in vivo models TAM suppressed constitutive, as well as carcinogen-induced proliferation, expression of mammary tumor virus-associated reverse transcriptase activity and decreased the incidence and frequency of mammary hyperplastic alveolar nodules. In the in vitro models TAM suppressed carcinogen-induced DNA damage, altered cellular metabolism of estradiol favoring the formation of less estrogenic catechols, and down-regulated anchorage-independent growth that is induced by ras oncogene and chemical carcinogen. Effective down-regulation of specific proliferative and metabolic biomarkers that are perturbed in mammary cell prior to tumorigenesis provides evidence that altered cellular metabolism of E2 may, in part, be responsible for antiproliferative and prophylactic properties of TAM against mammary tumorigenesis. PMID- 7982242 TI - Ethical issues: changing attitudes and practices. AB - Ethical questions about the conduct of cancer prevention research need to be addressed at individual, organizational, community, and national levels. These questions have been highlighted by the demands of women and minorities to be included in research, the participation of practicing clinicians in prevention research, the lack of consensus about the nature of the contract between participants and investigators, the locus of liability for public health interventions, the degree of safety needed for preventive interventions, the relative certainty needed to classify participants at high enough relative risk to be exposed to toxic or potentially toxic agents. A number of ongoing chemoprevention and behavioral intervention U.S. trials are used to illustrate these issues. A question will also be raised about the extent to which future preventive programs are determined by current decisions about priorities for research funding and whether these priorities match national needs and public preferences. PMID- 7982243 TI - [Transesophageal echocardiography in patients with ischemic stroke with and without clinical evidence of heart disease]. AB - Transesophageal echocardiography (TEE) is useful in the assessment of potential cardiac sources of emboli in patients with ischemic stroke and clinical history of heart disease. Aim of our study was to assess the utility of TEE in stroke patients with and without clinical evidence of cardiac disease. In addition, we evaluated if multiplane TEE, versus mono and biplane TEE, provides additional information about potential cardiac sources of emboli. A total of 89 ischemic stroke patients were studied: 30 patients with a history and clinical evidence of cardiac disease (Group A) and 59 patients without evidence of cardiac disease (Group B). All patients had a documented ischemic lesion of the brain. Patients who had an extracardiac potential source of emboli were excluded from the study. In all patients, transthoracic (TTE) and biplane TEE were performed, whereas omniplane TEE was performed in 40 patients only. In Group A, sources of emboli were disclosed by TTE in 33% of the patients. When TEE was performed the percentage of positive cases raised to 83% (p < 0.001). In Group B, TTE was positive in only 10% of the patients as opposed to 43% with TEE (p < 0.001). Omniplane TEE revealed a potential source of emboli in 23 out of 40 (57%) patients versus 16/40 (40%) and 20/40 (50%) with monoplane and biplane, respectively. TEE is useful in patients with cardiovascular disease in whom clinical evaluation and TTE are negative for sources of emboli. TEE is of great value in stroke patients without clinical evidence of cardiovascular disease in whom an extracardiac potential source of emboli has been excluded.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7982244 TI - [Chronology of regression of hypertensive ventricular hypertrophy during antihypertensive therapy with beta blockers]. AB - To define the time course of regression of left ventricular hypertrophy (LVH) during antihypertensive therapy with beta-blocking agents, 73 hypertensive patients were serially studied by echocardiography during 12-months therapy with beta-blockers. Blood pressure decreased significantly after 1 month and further on after 12 months (from 164 +/- 18/110 +/- 9 to 139 +/- 14/94 +/- 7 mmHg, p < 0.001). Left ventricular (LV) end-diastolic dimension increased significantly after 1 month (from 51.2 +/- 3.9 to 52.2 +/- 4.7 mm, p < 0.01) and decreased after 12 months (50.4 +/- 4.0 mm, p < 0.05). Septal and posterior wall thickness decreased progressively after 1 month and 3 months, respectively. LV mass index decreased significantly after 3 months, and further on after 12 months (from 164 +/- 42 to 145 +/- 33 g/m2, p < 0.001). LV fractional shortening did not significantly change throughout the study. Thus, a reduction of hypertensive LVH occurred after 3 months of therapy with beta-blocking agents and went on during the subsequent months without impairment of LV systolic function. PMID- 7982245 TI - Prognostic significance of basement membrane antigens and of soluble interleukin 2 receptor serum concentrations in heart transplant rejection. AB - Endomyocardial biopsy is still considered the only reliable method for diagnosing acute rejection. However, because of its invasive nature, this procedure cannot be performed on a daily basis. Therefore, for the noninvasive monitoring of transplanted patients, we tested the sensitivity of serum levels of basement membrane antigens, type IV collagen fragment NC1 and laminin fragment P1 (LP1), of antibodies against laminin and type IV collagen, and of soluble interleukin 2 receptor (sIL2R). In 17 patients who underwent heart transplantation no correlation was found between the degree of rejection and the levels of antibodies to type IV collagen and laminin. Serum laminin P1 and sIL2-R values were found increased in all the study groups even in absence of rejection; however, sIL2R levels were higher in patients with more severe rejection. NC1 levels were found significantly higher in patients with mild or moderate rejection than in those with no rejection or in controls. These preliminary data suggest a possible predictive role of basement membrane antigens in cardiac rejection, but further studies in a larger group of transplanted patients are needed. PMID- 7982246 TI - [Recovery of mechanical atrial function following atrial fibrillation]. AB - To evaluated the recovery of atrial function following atrial fibrillation, we followed 66 patients with atrial fibrillation cardioverted to sinus rhythm. Over 3 months of follow-up we performed transmitral pulsed Doppler echocardiography. The results were evaluated according to the etiology, duration of atrial fibrillation, left atrial dimension and modality of cardioversion. We observed a significant increase in both peak A wave velocity and percent atrial contribution to total left ventricular filling after 1 month in hypertensive patients and after 3 months in ischemic patients. The recovery of atrial mechanical function was earlier in patients with recent atrial fibrillation (< 24 hours) and in patients with normal left atrium. These results may have implications in guiding the duration of anticoagulant therapy after cardioversion. PMID- 7982247 TI - [Relations between acute myocardial edema, coronary vascular resistance and left ventricular mechanics in isolated rat heart]. AB - To evaluate the effect of acute myocardial edema (ME) on coronary vascular resistance (CVR) and left ventricular (LV) mechanical function, the LV water content (% of total weight) of seven groups (n = 10 each) of isolated rat heart was determined. Group I included non-perfused hearts and served as control. Group II was perfused with Krebs-Henseleit buffer only for the brief equilibration period which preceded every experiment. Group III, IV and V were perfused for 90 min at the constant pressure of 60, 100 and 140 mmHg respectively. Group VI and VII were perfused for 90 min at the constant flow of 10 and 30 ml/min respectively. The hearts were contracting isovolumically against a fluid-filled latex balloon with fixed volume. CVR and LV functional parameters were measured throughout the whole perfusion period. The water content of Group I (78.2 +/- 0.3%) was significantly lower than Group II (80.5 +/- 0.3%). A higher degree of ME was present in groups III, IV and V (80.2 +/- 0.3, 81.4 +/- 0.3 and 83.3 +/- 0.2%, respectively), as well as in groups VI and VII (80.7 +/- 0.1 and 83.4 +/- 0.2%, respectively). CVR significantly increased over time in groups III, IV and V (about +30, +35 and +50%, respectively), as well as in groups VI and VII (about +22 and +20%, respectively). LV developed pressure did not change over time in Group III (which did not show further fluid accumulation after the equilibration period); it decreased on the other hand in groups IV (about -27%) and V (about 40%). In groups VI and VII, LV developed pressure showed as increase (about +28%) and a reduction (about -29%) respectively. In conclusion, in the isolated crystalloid-perfused rat heart, ME is directly dependent on coronary perfusion pressure and/or flow. ME induces an increase in CVR and a rapid and significant depression of LV function. PMID- 7982248 TI - [Physiopathological and clinical aspects of ischemic cardiopathy in the aged]. PMID- 7982249 TI - Meta-analysis in the evaluation of treatment for streptococcal pharyngitis: a review. AB - Penicillin has been first-line therapy for the treatment of streptococcal pharyngitis for more than 40 years. Since the 1980s, there have been a number of reports suggesting that bacteriologic failure rates with penicillin may be rising. A number of alternative therapies have been proposed, including oral cephalosporins. To evaluate the efficacy of these agents, two meta-analyses have recently been performed. In the meta-analysis performed by Pichichero and Margolis, oral cephalosporins were reported to achieve a significantly greater bacteriologic cure rate than penicillin (92% with cephalosporins vs 84% with penicillin, P < 0.0001) when results from 19 studies were analyzed. A separate meta-analysis performed by Deeter et al reported that the oral cephalosporin cefadroxil monohydrate achieved significantly greater bacteriologic cure rates (94.8% cefadroxil vs 87.5% penicillin, P < 0.05) than oral penicillin when 9 trials in 1406 patients with streptococcal pharyngitis were analyzed. A review of 65 studies of the use of penicillin for the treatment of streptococcal pharyngitis has shown that bacteriologic failure rates in the period 1980 to 1993 were approximately 12% to 13%, slightly but not significantly greater than during the period 1953 through 1979. Oral cephalosporins such as cefadroxil monohydrate provide reasonable alternatives for the treatment of streptococcal pharyngitis. PMID- 7982250 TI - Safety of bronchodilator therapy in pediatric asthma patients. AB - This article reviews the drugs used in the treatment of childhood asthma (bronchodilators and anti-inflammatory agents) from the perspective of their safety and clinical tolerability. Adverse events observed in adults are likely to be seen to a greater degree in children and adolescents for many types of antiasthma drugs. It is clear that current therapy in childhood asthma is based on finding an optimal balance between efficacy and risk of side effects. In this regard, the fast-acting beta 2-adrenergic agonists, exemplified by albuterol, find a prominent place in therapy. Inhaled corticosteroids are also effective and well-tolerated first-line agents. Other bronchodilators (theophylline, ipratropium, slow-acting beta 2-agonists) and anti-inflammatory agents (cromolyn, nedocromil) should be added as required to control the condition, always keeping risk/benefit considerations in mind. PMID- 7982251 TI - Efficacy and tolerability of extended-release felodipine and extended-release nifedipine in patients with mild-to-moderate essential hypertension. AB - The efficacy and tolerability of extended-release felodipine (felodipine-ER) and nifedipine gastrointestinal therapeutic system (nifedipine GITS) were compared in a multicenter, prospective, open-label clinical trial of 277 patients with mild to-moderate uncomplicated essential hypertension (sitting diastolic blood pressure [SiDBP] > or = 95 and < or = 115 mm Hg). After a 3-week washout period, patients were randomized to receive felodipine-ER (5 mg once daily) or nifedipine GITS (30 mg once daily); during a subsequent 6-week titration phase, the once daily felodipine-ER dose could be increased to 10 mg and the nifedipine GITS dose to 60 or 90 mg in an attempt to achieve adequate blood pressure response (SiDBP < or = 90 mm Hg, or < 100 mm Hg with a > 10-mm Hg reduction from baseline, as measured 24 hours after dosing [trough]). At the end of titration, the mean daily doses of felodipine-ER and nifedipine GITS were 8 and 50 mg, respectively. Mean changes in sitting systolic blood pressure (SiSBP)/SiDBP were -14/-12 and -16/-13 mm Hg, respectively. All reductions were significant when compared with baseline (P < 0.01), but there were no significant differences between treatment groups. Adequate blood pressure response occurred in 77% of the felodipine-ER group and 80% of the nifedipine GITS group; this difference was not significant. Blood pressure changes were similar among sex and race subgroups. A higher percentage of older patients (> 55 years of age) than younger patients (< or = 55 years of age) reached goal SiDBP with both drugs. Patients with adequate SiDBP response continued receiving their assigned medication for an additional 6-week maintenance period. Reductions in SiDBP and SiSBP from baseline continued to be significant in both treatment groups. No clinically important changes in heart rate were noted. A total of 28 patients (15 in the felodipine-ER group and 13 in the nifedipine GITS group) withdrew from the study because of inadequate blood pressure response. At least one adverse experience occurred in 55% of the felodipine-ER group and 63% of the nifedipine GITS group, prompting withdrawal of 14 patients (10%) and 16 patients (11%), respectively. Headache and edema were the most common adverse experiences. The incidence and pattern of adverse experiences did not differ significantly between treatments. The results of this study demonstrate that once-daily felodipine-ER and nifedipine GITS are similarly highly effective and generally well tolerated in patients with essential hypertension. PMID- 7982252 TI - A large, prospective, open-label study of isradipine in patients with essential hypertension. The Isradipine Investigators Group. AB - Isradipine is a dihydropyridine calcium-entry blocker. Previous controlled and blinded trials have demonstrated the safety and efficacy of isradipine in lowering blood pressure in patients with hypertension. The purpose of this study was to reassess this safety and efficacy in a large number of patients in an open label, long-term, multicenter trial. A total of 501 patients with essential hypertension (diastolic blood pressure 95 to 114 mm Hg) received 5 to 10 mg/d of isradipine in two divided doses for a period of 32 weeks. The mean dose used was 7.4 mg/d with titration at week 4 from 5 mg/d (2.5 mg BID) to 10 mg/d (5 mg BID) if the diastolic pressure was still > 90 mm Hg. After 32 weeks of isradipine treatment, systolic blood pressure decreased from 154.9 +/- 16.4 mm Hg to 140.2 +/- 13.9 mm Hg (P < 0.001) and diastolic pressure from 101.2 +/- 5.2 mm Hg to 86.6 +/- 7.9 mm Hg (P < 0.001). This monotherapy was successful in reducing diastolic blood pressure > 10 mm Hg in 62.5% of the patients. Significant adverse effects were noted in 92 (18.4%) of the 501 patients; only 30 (6.0%) withdrew from the study because of adverse events. In this large, long-term, community based study, isradipine was effective and well tolerated in most patients. PMID- 7982253 TI - Controlled study of brodimoprim and cephalexin in the treatment of patients with acute sinusitis in general practice. AB - Brodimoprim, a new dehydrofolate reductase inhibitor, was compared with cephalexin in the treatment of patients with acute sinusitis. A total of 49 patients were randomly assigned to receive either brodimoprim 200-mg tablets once a day (400 mg on the first day as a loading dose) or cephalexin 500-mg tablets three times a day for 8 to 12 days. Nearly all patients treated were judged clinically cured/improved; in fact, only one failure (in the cephalexin group) was noted. In the 45 assessable patients, the time until disappearance of the symptoms and the duration of treatment did not differ significantly between the two groups. A bacteriologic examination was performed in all patients at baseline as well as at the end of therapy. Bacteriologic eradication was obtained in 88% of the patients treated with brodimoprim and in 76% of those receiving cephalexin. Both compounds were generally well tolerated (one patient in the brodimoprim group complained of skin reactions). These results suggest that once daily treatment with brodimoprim represents safe and effective therapy for adults with acute bacterial sinusitis. PMID- 7982254 TI - A comparison of ampicillin/sulbactam and cefuroxime in the treatment of patients with bacterial infections of the lower respiratory tract. AB - Ampicillin/sulbactam (1 to 2 g ampicillin and 0.5 to 1 g sulbactam, administered intravenously once every 6 hours) and cefuroxime (750 mg to 1.5 g, administered intravenously once every 8 hours) were compared to determine their efficacy and safety in treating patients with lower respiratory tract infections of bacterial etiology. Nineteen of the 41 patients treated with ampicillin/sulbactam and 18 of the 44 patients treated with cefuroxime were assessable for efficacy. The clinical responses to the 2 treatments were comparable: 5 (26%) patients treated with ampicillin/sulbactam were cured and 14 (74%) were improved. Five (28%) patients who received cefuroxime were cured, 12 (67%) were improved, and treatment failed in 1 patient (6%) (P = 0.569). Similarly, no significant difference was noted between the bacteriologic responses to the two antimicrobials (P = 0.486). All isolates from the patients treated with ampicillin/sulbactam were eradicated, as were all isolates in 17 (94%) of the patients treated with cefuroxime. A superinfection occurred in 1 (6%) patient who received cefuroxime. Adverse reactions were rare and occurred in 3 patients from each treatment group. PMID- 7982255 TI - The effects of pentoxifylline on the prevention of cyclosporine-induced nephrotoxicity in cardiac transplant patients. AB - The objective of this trial was to determine if oral pentoxifylline (PTX) reduced cyclosporine (CSA)-induced renal dysfunction in cardiac transplant patients in the 8 months following transplantation. The study was a prospective, open-label, crossover trial evaluating the renal effects of PTX in nine postcardiac transplant patients. Patients received PTX 2 weeks posttransplant and continued therapy for 4 months. Patients were evaluated for an additional 4 months thereafter. During the trial, various renal function tests were performed and CSA concentrations were measured at set intervals. Baseline measurements were compared with all subsequent measurements. In addition, "on-PTX" data were compared with "off-PTX" data. Significant alterations in results of renal function tests were not seen during the trial when compared with baseline values. Although no significant changes in renal function were observed during the study, no patient developed CSA-induced acute renal failure during the 4 months posttransplant. This finding suggests that PTX may offer a nephroprotective effect against CSA-induced toxicity. PMID- 7982256 TI - Effects of ulinastatin on polymorphonuclear leukocyte elastase and interleukin 6 levels after hepatectomy. AB - Eight patients undergoing hepatectomy received 15 x 10(4) U of ulinastatin during and after surgery and then twice daily for 4 days, and 11 hepatectomized patients served as untreated controls. Between-group differences in age, duration of surgery, volume of blood loss and transfusion, weight of resected liver, and results of preoperative liver function tests were not significant. On postoperative day 1, mean (+/- SD) polymorphonuclear leukocyte elastase levels were significantly lower in the treated patients than in the controls (310 +/- 69 micrograms/L vs 519 +/- 382 micrograms/L; P < 0.05); interleukin 6 levels also tended to be lower in the treated patients than in controls (42.4 +/- 34.0 pg/mL vs 63.3 +/- 43.1 pg/mL). The results indicate that ulinastatin has beneficial effects on host defenses after surgery. PMID- 7982257 TI - Pharmacokinetic comparison of a once-daily and twice-daily theophylline delivery system. AB - The steady-state pharmacokinetics of a formulation of a 24-hour extended-release theophylline preparation (Uni-Dur) were compared with a twice-daily formulation (Theo-Dur) in healthy volunteers. Eighteen healthy, adult, male volunteers received both treatments (600-mg dose of Uni-Dur every morning for 5 doses or 300 mg every 12 hours for 10 doses of Theo-Dur) in a randomized, two-way crossover design with no washout period between treatments. Blood samples were collected just before doses 3, 4, and 5 of Uni-Dur and before doses 5, 7, and 9 of Theo Dur, as well as at 2-hour intervals for 24 hours following doses 5 of Uni-Dur and doses 9 and 10 of Theo-Dur. The mean serum theophylline concentration-time curves were similar for both formulations from 2 to 18 hours postdose, and the maximum serum theophylline concentrations were comparable (7.66 micrograms/mL for Uni-Dur compared with 7.78 micrograms/mL for Theo-Dur). Fluctuations in serum theophylline concentrations were greater with Uni-Dur (139 +/- 85% compared with 72 +/- 25% normalized to trough serum concentrations; 77 +/- 22% compared with 53 +/- 13% normalized to average steady-state serum concentrations). Based on the area under the curves, the extent of absorption of Uni-Dur was 91.42 +/- 14.24% of Theo-Dur. These findings suggest that the clinical response in patients treated with once-daily Uni-Dur may be equivalent to Theo-Dur given every 12 hours. Furthermore, because of the similar serum concentration over time profiles of the two formulations, it is unlikely that additional monitoring of serum levels during a conversion will be necessary. PMID- 7982258 TI - The international consensus report on diagnosis and treatment of asthma: a call to action for US practitioners. AB - Effective management of asthma requires accurate diagnosis and assessment of the severity of the disease. Subjective measures, such as the degree of cough, wheezing, and chest tightness, and objective assessments of pulmonary function, provide diagnostic evidence of the presence of asthma. The diagnostic criteria included in the International Consensus Report on Diagnosis and Treatment of Asthma provide one method of classifying asthma by the degree of severity. These guidelines, which were developed by the National Institutes of Health in collaboration with the International Asthma Management Project, include the US Guidelines for the Diagnosis and Management of Asthma. Only the mildest, intermittent cases of asthma generally can be managed with an inhaled short acting beta 2-agonist given alone as needed. As the frequency or severity of the asthma increases, inhaled corticosteroids, inhaled cromolyn, or inhaled nedocromil should be added to the treatment regimen. Sustained-release theophylline, long-acting oral or inhaled beta 2-agonists, and inhaled anticholinergic agents also have a place in the treatment of selected patients. PMID- 7982259 TI - A cost-benefit analysis of four hormonal contraceptive methods. AB - This paper presents the results of a cost-benefit analysis conducted for pregnancy prevention treatment with four hormonal methods of contraception using a managed-care viewpoint. The therapies analyzed are medroxy-progesterone acetate injection (Depo-Provera), levonorgestrel subdermal implants (Norplant), progestogenonly oral tablets (Nor-QD), and combination progestogen/estrogen oral tablets (Ortho-Novum 7/7/7). Cost and benefits associated with the use of therapies are identified and analyzed based on the cost per patient-day of effective pregnancy prevention. The analysis demonstrates that all four methods have a positive net benefit, with Depo-Provera having the highest net benefit. This information can provide decision makers within a pharmacy and therapeutics committee of a managed-care organization the framework on which to base formulary decisions. PMID- 7982260 TI - Antidepressant pharmacotherapy: economic outcomes in a health maintenance organization. AB - Recent pharmacotherapeutic advances in the treatment of depression have included the development of selective serotonin re-uptake inhibitors (SSRIs). The present study was designed to contrast direct health service expenditures for the treatment of depression among patients enrolled in a health maintenance organization (HMO) and prescribed either the SSRI fluoxetine or one of three tricyclic antidepressants (TCAs) (amitriptyline, nortriptyline, or desipramine). Information regarding health service utilization was derived from the computer archive of a network-model HMO system serving 400,000 beneficiaries. A total of 701 HMO beneficiaries were found to satisfy the study selection criteria. Multivariate regression analysis was used to discern the incremental influence of selected demographic, clinical, financial, and provider characteristics on 1 year post-period expenditures (PPE) for health care. Analysis-of-variance procedures with Duncan's multiple-range test, or chi-square analyses, revealed no significant difference across antidepressant pharmacotherapy for age, sex, 6 month prior-period expenditures for physician visits, psychiatric visits, laboratory tests, hospitalizations, or psychiatric hospital services related to the treatment of depression, or number of prescribed therapeutic agents for disease state processes other than depression. Receipt of fluoxetine was associated with a significantly (P < or = 0.05) higher rate of initial prescribing by psychiatrists, an increase in the number of prescriptions for antidepressant pharmacotherapy obtained (30-day supplies), and a reduction in the number of monthly intervals during which time antidepressant pharmacotherapy was not procured. Receipt of fluoxetine as antidepressant pharmacotherapy was associated with a significantly (P < or = 0.05) higher mean medication possession ratio (MPR) relative to amitriptyline, nortriptyline, or desipramine. Multivariate findings for patient-level data reflecting a definitive diagnosis of depression (n = 555) indicate that receipt of a TCA resulted in a significant (P < or = 0.05) increase in the use of physician visits ($36.07), psychiatric visits ($41.38), laboratory tests ($1.71), hospitalizations ($208.77), and psychiatric hospital services ($187.27), and a significant (P < or = 0.05) reduction in expenditures for antidepressant pharmacotherapy (-$162.21), for a total increase in health service utilization of $312.99 (P < or = 0.05) 1 year post-initiation of antidepressant pharmacotherapy.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7982261 TI - Calcium-sequestering organelles of Dictyostelium discoideum: changes in element content during early development as measured by electron probe X-ray microanalysis. AB - Starving Dictyostelium discoideum amoebae aggregate within a few hours by chemotaxis towards the attractant cAMP to form a multicellular organism. The differentiating cells possess rapid and efficient calcium buffering and sequestration systems which enable them to restrict changes in the cytosolic free calcium concentration temporally and spatially during their chemotactic reaction and allow the continuous accumulation of Ca2+ during development. In order to identify and to characterize calcium storage compartments, we analyzed the element content of amoebae at three consecutive stages of differentiation. Determination of the element distribution was done using energy-dispersive X-ray microanalysis of freeze-dried cryosections of rapid-frozen cells. Amoebae were frozen in the vegetative and aggregation-competent state and after formation of aggregates. Aggregation-competent as well as aggregated cells contained mass dense granules with large amounts of calcium together with phosphorous and either potassium or magnesium: in aggregation-competent cells calcium was colocalized with potassium, whereas in aggregated cells the mass dense granules contained calcium and magnesium. Although mass dense granules were also present in undifferentiated, vegetative cells, they contained only low amounts of phosphorous and potassium together with little Ca and Mg. We conclude that during their differentiation D. discoideum cells use an intracellular storage compartment to sequester Ca and other cations constantly throughout development. PMID- 7982262 TI - Activation of phosphoinositide metabolism by parathyroid hormone in growth plate chondrocytes. AB - Parathyroid hormone (PTH) is one of the most potent stimulators of growth plate chondrocyte mitogenesis that has been reported. However, study of the second messenger signaling mechanisms involved in the transduction of the hormone's effects on these cells is incomplete. Our data indicate that in addition to stimulating cyclic adenosine-3'5'-monophosphate metabolism, PTH also activates the phosphoinositide cascade, the pathway responsible for the generation of inositol-1,4,5-trisphosphate dependent Ca2+ signals. Our conclusion that PTH activates the phosphoinositide cascade is based on data that demonstrate: (1) the Ca2+ transients evoked by the hormone are dependent on intracellular Ca2+ stores; (2) the hormone stimulates the release of radiolabeled inositol from GPC plasma membranes; and (3) the hormone stimulates a greater than 8-fold increase in cytosolic inositol-1,4,5-trisphosphate pool size. PMID- 7982263 TI - Measurement of sarcoplasmic reticulum calcium content in skinned mammalian cardiac muscle. AB - We developed an optical system for the measurement of the Ca2+ content of sarcoplasmic reticulum (SR) in saponin-treated ventricular muscles of ferrets. After the SR was loaded with Ca2+ by activating the Ca2+ pump of SR, caffeine (50 mM) was applied to release the accumulated Ca2+ from the SR into the bathing solution containing the fluorescent Ca2+ indicator, Fluo-3. As Fluo-3, at high concentrations (approximately 200 microM), predominantly binds most of the Ca2+ released from the SR, the Fluo-3 fluorescence change upon Ca2+ binding gave an estimate of the amount of accumulated Ca2+ in SR before caffeine application. The maximal Ca2+ content of SR, thus estimated, was about 370 mumol/l cytoplasm. The amount of Ca2+ loaded in SR showed bell-shaped dependence on the free Ca2+ concentration ([Ca2+]) of the loading solution, reflecting Ca(2+)-induced Ca2+ release at high [Ca2+] (> or = 1 microM). Mg2+ and H+ decreased the rate of Ca2+ uptake by SR. The present system provides a relatively direct means of measurement of the Ca2+ content of SR, and allows examination of the effects of various interventions on SR Ca2+ uptake, bypassing the large influence of intracellular Ca2+ buffer sites. PMID- 7982264 TI - Activation of calcium and calmodulin dependent protein kinase II during stimulation of insulin secretion. AB - Pancreatic islets contain an alloxan sensitive, calcium and calmodulin dependent protein kinase (CaM-PK) which may play an important part in the cellular control of insulin secretion. We have studied this activity in islets and the insulin secreting tumor cell line RINm5f with particular interest in the changes in kinase activity that accompany stimulation of secretion. Initial experiments showed that the CaM-PK activity enriched in microsomal preparations from RIN cells was similar to the islet cell kinase in terms of apparent endogenous substrates, Ca2+ and calmodulin dependence, and inactivation by alloxan. For studies of protein substrate specificity, tumor cell CaM-PK was isolated from other kinase activities and substantially purified by affinity chromatography with calmodulin-agarose. The major protein substrates of CaM-PK (54 kD and 57 kD) co-purified with the kinase activity, representing autophosphorylation of subunits of the enzyme. Exogenous substrates phosphorylated by these preparations included microtubule-associated protein 2, synapsin, and glycogen synthase; this pattern of substrate utilization identified the kinase as the Type II multifunctional kinase which has been extensively characterized in brain. A polyclonal antibody to rat brain CaM-PK II was employed to immunoprecipitate the kinase from RINm5f cells incubated with secretagogues to measure the effect of stimulation of secretion on autophosphorylation of CaM-PK (which reflects kinase activation). D-Glyceraldehyde (22 mM) and depolarizing concentrations of potassium increased autophosphorylation and insulin secretion in a parallel fashion. Potassium stimulated autophosphorylation was dose dependent and saturable, and was increased to near maximal levels at times as short as 1 min. These studies demonstrate that pancreatic islets and RINm5f cells contain a Type II CaM-PK which is activated during the secretion process. PMID- 7982265 TI - Bradykinin-stimulated calcium mobilization in cultured canine tracheal smooth muscle cells. AB - Bradykinin (BDK)-induced increases in intracellular Ca2+ concentration ([Ca2+]i) were monitored in cultured canine tracheal smooth muscle cells (TSMCs) using a fluorescent Ca2+ indicator, Fura-2. BDK and kallidin caused an initial transient peak followed by a sustained elevation of [Ca2+]i in a concentration-dependent manner, with half-maximal stimulation (log EC50) obtained at -8.10 M and -8.04 M, respectively. The BDK-induced rise in [Ca2+]i was not affected by the BDK B1 receptor antagonist, des-Arg9[Leu8]-BDK (10 microM). However, the BDK B2 receptor antagonists des-Arg[Hyp3, Thi5,8, D-Phe7]-BDK and Hoe 140 had high affinity in antagonizing BDK with pKB values of 7.5 +/- 0.3 and 8.7 +/- 0.3, respectively. The sustained phase of the rise in [Ca2+]i was dependent on the presence of external Ca2+, as evidenced by a decline to the resting level on addition of EGTA. In the absence of external Ca2+, only an initial transient peak was seen which then declined to the resting level; a sustained elevation of [Ca2+]i could then be evoked by addition of 1.8 mM Ca2+ in the continued presence of BDK. Ca2+ influx was required for the changes in [Ca2+]i, since Ca(2+)-channel blockers, diltiazem, verapamil, and Ni2+, decreased both the initial and sustained elevation of [Ca2+]i in response to BDK. In conclusion, these findings indicate that the initial increase in [Ca2+]i stimulated by BDK acting on BDK B2 receptors is due to the release of Ca2+ from internal stores, followed by the influx of external Ca2+ into the cells. The influx of extracellular Ca2+ partially involves a diltiazem- and verapamil-sensitive Ca2+ channel. PMID- 7982266 TI - Ca2+ stores in insulin-secreting cells: lack of effect of cADP ribose. AB - Ca2+ stores were examined in several insulin secreting cell types by measuring uptake and release of Ca2+ by permeabilised cells. In pancreatic islet cells or INS-1 cells, < 20% of the ATP-dependent, thapsigargin-sensitive Ca2+ pool could be released by saturating concentrations of inositol (1,4,5)P3 (InsP3). InsP3 released > 60% of the thapsigargin-sensitive Ca2+ pool in RINm5F cells. The total Ca2+ content of the thapsigargin-sensitive pool was similar in each of these cell types. Neither cADP ribose (cADPR; 1 microM) nor caffeine (10 mM) caused significant Ca2+ release from any of the permeabilised insulin-secreting cell preparations. ATP elicited similar increases in intracellular Ca2+ concentration ([Ca2+]i) in single, living INS-1 and RINm5F cells, and similar fold increases in InsP3 levels in cell populations. The Ca2+ ATPase inhibitor thapsigargin, added after ATP, caused smaller [Ca2+]i increases in RINm5F than in INS-1 cells. This is consistent with the presence of a smaller InsP3-sensitive Ca2+ pool in living INS-1 cells. The data indicate that InsP3 receptors are present in only a small subfraction of the Ca2+ ATPase-containing Ca2+ stores in INS-1 and pancreatic beta-cells, and that cADP ribose/caffeine-sensitive Ca(2+)-induced Ca2+ release channels may be entirely absent from this endocrine cell type. PMID- 7982267 TI - Effect of short and long term streptozotocin diabetes on smooth muscle calmodulin levels in the rat. AB - Diabetes mellitus is a metabolic disease associated with certain complications which have also been demonstrated in the experimental models of this disease. Altered responses to several agonists have been reported in various smooth muscles from alloxan or streptozotocin diabetic animals. Since these reports revealed a defect in the contractile process of smooth muscles from experimentally-induced diabetes, short and long term effects of diabetes on calmodulin levels in the smooth muscles of aorta, trachea, vas deferens and duodenum were investigated using streptozotocin diabetic rats. In spite of the fact that most of the reports have demonstrated the defective contractions in long term diabetic rats, short term effect (for 1 week) of diabetes on calmodulin levels in the smooth muscles of aorta, trachea, vas deferens and duodenum was also investigated in the present study using streptozotocin diabetic rats to understand whether the changes in calmodulin dependent contractile process begin at an earlier stage of the disease. Tissue calmodulin levels of the smooth muscles were measured by the radioimmunoassay technique using a [125I]-labeled kit. Although rats injected with streptozotocin exerted the characteristics of diabetes such as polyuria, polydipsy, polyphagy and elevated blood glucose levels, unchanged calmodulin levels were found in the rats with short term streptozotocin diabetes. In contrast, long term streptozotocin diabetes (for 8 weeks) was found to cause a significant decrease in tissue calmodulin levels of these four smooth muscles.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7982268 TI - Intracellular Ca2+ transients in isolated perfused rat heart: measurement using the fluorescent indicator Fura-2/AM. AB - We have investigated the nature of Fura-2/AM loading into isolated perfused rat heart and the temporal and kinetic relationship between left ventricular [Ca2+]i dependent fluorescence and isovolumic pressure. The contribution of hydrolysed mitochondrial matrix Fura-2 fluorescence to that measured from the surface of the heart was estimated to be 43.9 +/- 5.5% by the addition of 100 microM Mn2+ to the perfusate. Maximum endothelial Fura-2 fluorescence ratio, estimated by the addition of 3 microM bradykinin to the perfusate, was found to constitute 33.6 +/ 2.7% of the maximum myocardial Fura-2 fluorescence ratio. Approximately 11.2% of the 340 nm surface fluorescence was insensitive to 20 mM Mn2+ in the presence of ionomycin (3 microM) and therefore indicates the degree of partial hydrolysis of Fura-2/AM. Thus, depending on the contribution of endothelial Fura-2 fluorescence at a physiological endothelial calcium concentration, cytosolic fluorescence may comprise between 11-45% of the total cellular fluorescence at 340 nm. Net tissue interference of the Fura-2 fluorescence ratio by NADH emission and myoglobin absorption remained unaltered, providing the oxygenation state of the tissue was unaltered throughout the experiment. The [Ca2+]i dependent fluorescence decay from peak systole was best fitted to a biexponential decay with fast and slow rate constants of 18.08 +/- 1.97 s-1 and 0.23 +/- 0.02 s-1, respectively. In addition, a phase shift was observed between temporal and kinetic measurements of the left ventricular isovolumic pressure and calcium dependent fluorescence traces during a contraction-relaxation cycle. We conclude that despite imperfect Fura-2/AM loading, the temporal and kinetic characteristics of intracellular [Ca2+] transients in normal isolated perfused rat heart are similar to those reported in more controlled preparations such as isolated myocytes and cardiac trabeculae. PMID- 7982269 TI - Contribution of tumor necrosis factor-alpha and glucocorticoid in hydrazine sulfate-mediated protection against endotoxin lethality. AB - Hydrazine sulfate pretreatment has previously been shown in our laboratory to protect normal mice against endotoxin and D-galactosamine-sensitized mice against both exogenous tumor necrosis factor (TNF) and endotoxin. An intact pituitary is required for manifestation of the protective effects. Further, we have demonstrated that hydrazine sulfate pretreatment specifically modulates the TNF response to lipopolysaccharide (LPS) in mouse macrophages in vitro. This in vivo study was performed to test whether a reduced TNF response and/or increased glucocorticoid response may contribute to hydrazine sulfate protection against LPS-induced lethality in vivo. The results presented here establish that hydrazine sulfate pretreatment selectively attenuates circulating TNF levels following LPS challenge. Moreover, adrenalectomy abrogates hydrazine sulfate protection but does not prevent hydrazine sulfate attenuation of circulating TNF levels in response to LPS. Hydrazine sulfate-mediated protection is, however, restored permissively by corticosterone. Thus, the mechanism by which hydrazine sulfate protects against LPS lethality in adrenalectomized mice includes TNF modulation in response to endotoxin, as well as a pivotal requirement for glucocorticoid. PMID- 7982270 TI - Tumor necrosis factor alpha regulation of immunoglobulin secretion in trauma patients. AB - Major trauma-related immune dysfunction is observed at the time of augmented release of immunopathologic mediators. In the present study, T cell-dependent immunoglobulin (Ig) synthesis in peripheral blood mononuclear cell (PBMC) cultures from blunt trauma patients (N = 12, injury severity score (ISS) 27-50), was reduced by 30- > 90%. This coincided with significantly (P < 0.001-0.01) elevated secretion of the biologically active tumor necrosis factor alpha (TNF alpha). Modulation of the TNF alpha activity by anti-TNF alpha antibody (anti-TNF alpha Ab) led to dose-dependent alterations in IgG synthesis. IgG production increased (up to 300%) in cultures treated with 0.5-2 micrograms/ml of the antibody, where low levels of TNF alpha activity often persisted. However, immunoglobulin synthesis was eradicated in preparations exposed to higher concentrations (10 micrograms/ml) of anti-TNF alpha Ab and devoid of TNF alpha biological activity. The treatment with anti-TNF alpha Ab had no effect on mitogen- or alloantigen-induced PBMC proliferation. Thus, in severely traumatized patients, biological activities of endogenous TNF alpha may include modulation of T cell-dependent B lymphocyte function. Immunoregulatory potential of TNF alpha should, therefore, be considered in therapeutic strategies to abrogate its activity. PMID- 7982271 TI - Altered mitochondrial redox responses in gram negative septic shock in primates. AB - Gram negative sepsis causes changes in oxygen supply-demand relationships. We have used a primate model of hyperdynamic gram negative sepsis produced by intravenous infusion of Escherichia coli (E. coli) to evaluate sepsis-induced alterations in mitochondrial oxidation-reduction (redox) state in muscle in vivo. The redox state of cytochrome a,a3, the terminal member of the intramitochondrial respiratory chain, was assessed in the intact forearm by near-infrared (NIR) spectroscopy. The muscle NIR data were compared to routine measures of oxygen delivery (DO2) and oxygen consumption (VO2). After E. coli infusion and fluid resuscitation, DO2 and VO2 showed minimal changes through 24 hr of sepsis. In contrast, changes in cytochrome a,a3 redox state evaluated by NIR occurred within a few hours and were progressive. Mitochondrial functional responses were correlated with structural changes observed on serial muscle biopsies. Gross morphological changes in muscle mitochondria were present in some animals as early as 12 hr, and, in most animals, by 24 hr. The morphologic changes were consistent with decreases in oxidative capacity as suggested by NIR spectroscopy. The NIR data also suggest that two mechanisms are operating to explain abnormalities in oxygen metabolism and mitochondrial function in lethal sepsis. These mechanisms include an early defect in oxygen provision to mitochondria that is followed by a progressive loss in functional cytochrome a,a3 in the muscle. PMID- 7982272 TI - Use of gastric intramucosal pH as a monitor during hemorrhagic shock. AB - During resuscitation of the patient suffering from hemorrhagic shock, it may be difficult to determine the adequacy of treatment in the acute setting. The objective of these preliminary studies was to determine if monitoring perfusion of the gastrointestinal tract as estimated by gastric intramucosal pH (pHi) is useful as a guide during the treatment of hemorrhagic shock. Dogs were bled using a modified Wigger's method to a mean arterial blood pressure of 50 mmHg, and pHi was determined 30, 60, 90, and 120 min later. Gastric intramucosal acidosis developed within 30 min of induction of hemorrhagic shock. It was also found that pHi decreases with relatively small amounts of blood loss. There was a significant fall in pHi following hemorrhage to a mean arterial pressure of 80 mmHg from a baseline pressure of 100 mmHg. Following the reinfusion of shed blood, the pHi returned to baseline values within 30 min. It is concluded that measurements of pHi may be a useful monitor in the evaluation and initial resuscitation of patients in hemorrhagic shock. PMID- 7982273 TI - Priming of phagocytes for reactive oxygen production during hepatic ischemia reperfusion potentiates the susceptibility for endotoxin-induced liver injury. AB - Plasma levels of glutathione disulfide (GSSG) as an indicator of a vascular oxidant stress, tumor necrosis factor-alpha (TNF-alpha) formation, and liver injury (alanine aminotransferase activity, histology) were monitored in male Fischer rats after 30 min of hepatic ischemia followed by up to 4 hr of reperfusion. The injection of 1 mg/kg Salmonella enteritidis endotoxin at 30 min of reflow potentiated the postischemic oxidant stress and liver injury. TNF-alpha levels increased from 10 +/- 7 pg/ml (baseline) to 3,553 +/- 738 pg/ml after ischemia-reperfusion followed by endotoxin, or to 3,670 +/- 508 pg/ml after endotoxin alone. Depletion of serum complement before ischemia attenuated the endotoxin-mediated increase of reactive oxygen formation by 70% but did not affect TNF-alpha levels. Complement activation with cobra venom factor (CVF) during reperfusion had an effect similar to that of endotoxin on the oxidant stress and liver injury. CVF did not increase TNF-alpha formation during reperfusion. Kupffer cells and neutrophils isolated from the postischemic liver 2.5 hr after endotoxin injection generated 600% and 400% more superoxide, respectively, than cells isolated from control livers. The results demonstrate a substantial priming of hepatic phagocytes for reactive oxygen production but not TNF-alpha formation, even after short periods of hepatic ischemia, and the vulnerability of the postischemic liver to severe endotoxin-induced injury. Activated complement seems to be mainly responsible for the effects. These results may explain the high risk for hepatic failure after extensive liver resection and hypovolemic shock. PMID- 7982274 TI - Local neural control of intestinal motility: nerve circuits deduced for the guinea-pig small intestine. AB - 1. Propulsion of digesta along the intestine appears to occur by the action of a series of local reflexes which cause contraction oral to the digesta and relaxation of circular muscle on the anal side. 2. There is now substantial evidence available about the identities of the enteric neurons that mediate these reflexes. 3. The motor neurons and interneurons of the reflex pathways lie within the myenteric plexus. These neurons can be classified electrophysiologically as S neurons and have distinctive projections and neurochemistries. 4. The sensory neurons may lie in the myenteric plexus, but there is some evidence for sensory neurons in the submucous plexus. A contribution from extrinsic sensory neurons to local motility reflexes cannot be ruled out. Intrinsic sensory neurons are probably AH-neurons and are large multi-axonal cells. PMID- 7982275 TI - The vascular tissue angiotensin I-converting enzyme activity and aortic elastin content in stroke-prone spontaneously hypertensive rats fed fish diet. AB - 1. Stroke-prone spontaneously hypertensive rats (SHRSP) were fed a diet with fish meal as the protein source (fish diet) during the progressive stage of hypertension, and its effects on the activity of angiotensin I-converting enzyme (ACE) in serum and vascular tissues and on the aortic elastin content were studied. The effects of the antihypertensive drugs captopril and hydralazine were also studied. 2. Stroke-prone spontaneously hypertensive rats fed the fish diet showed a distinctly lower level (P < 0.05) of serum ACE activity than the control group fed a commercial stock chow. 3. ACE activity was enhanced in the SHRSP which was administered with captopril. 4. Serum ACE activity was similar in the SHRSP receiving the hydralazine treatment and the control group. 5. The thoracic aorta ACE activity was lowered more (P < 0.05) in the fish diet group and the captopril-treated group than in the control group. In the hydralazine-treated group however, the activity was similar to the control group. 6. The ratio of aorta weight to bodyweight was significantly lower (P < 0.05) in the fish diet group and the captopril-treated group than in the control group, but there was no difference in the hydralazine group. Higher levels of aortic elastin were observed in the drug-treated groups (P < 0.05). 7. No differences were seen between the fish diet and captopril-treated groups by electron-microscopy. 8. The results suggest that suppression of hypertrophy and ameliorations of reduction in elasticity of the vascular wall in the SHRSP fed a fish diet were due to inhibition of vascular tissue ACE activity. PMID- 7982276 TI - Angiotensin II receptor density in bovine ovarian follicles relates to tissue renin and follicular size. AB - 1. The purpose of this study was to investigate angiotensin II (AII) receptors in isolated bovine ovarian follicles and the relationship of their density to follicular concentrations of prorenin, active renin, oestradiol and progesterone. 2. Displacement of [125I]-[Sar1-Ile5-Ile8]-AII binding by the AII receptor antagonists PD 123319 and Losartan (DuP 753) confirmed that follicular AII receptors are of subtype 2 (AT2 receptor). 3. The dissociation constant (Kd) for [Ile5]-AII (human AII) was 0.84 (range 0.51-1.47) nmol/L. The receptor density varied between 90 and 5990 (mean 1640) fmol/mg membrane protein. 4. The follicular AII receptor density correlated positively with follicular diameter (Spearman's rho = 0.518; P < 0.003) and tissue weight (Spearman's rho = 0.636; P < 0.0001), and negatively with the active renin concentration in the follicular wall (Spearman's rho = -0.399; P < 0.02). The AII receptor density did not correlate with the follicular fluid concentrations of prorenin, active renin, oestradiol (E2), progesterone (P4) or the E2/P4 ratio. The follicular fluid concentrations of prorenin correlated negatively with the E2/P4 ratio (Spearman's rho = -0.716; P < 0.0001). 5. The inverse relationship between AII receptor density and the high active renin concentrations in the follicular wall suggests an active regulated tissue renin-angiotensin system. A high AII receptor density is a general feature of large bovine ovarian follicles. PMID- 7982277 TI - Alinidine prevents hypoperfusion-induced transmural flow redistribution in isolated paced rat hearts. AB - 1. The effect of alinidine on transmural flow redistribution during hypoperfusion was studied in the isolated rat heart. 2. Low flow perfusion of paced (5 Hz) rat Langendorff preparations with Tyrode's solution for 60 min resulted in loss of left ventricular pressure amplitude and contracture. 3. In the presence of 45.6 mumol/L alinidine in the hypoperfusion medium contractility was maintained and contracture was missing. 4. Myocardial sphere densities were assessed by infusion of fluorescent microspheres after 60 min of hypoperfusion. Histomorphometric evaluation of the left ventricular wall indicated marked redistribution of myocardial flow to the epicardium. Endo/epicardial quotients of sphere densities were significantly greater in alinidine-treated hearts. 5. Perfusion of hearts with 45.6 mumol/L alinidine for 30 min at a pressure of 80 cmH2O decreased coronary flow and contractility, but did not change the transmural quotient of sphere densities. 6. These results show that in isolated rat hearts with a ventricular wall of only 3-4 mm thickness severe hypoperfusion induces a shift in transmural flow distribution which is prevented by alinidine. PMID- 7982278 TI - Anti-obesity and anti-diabetic effects of carteolol in non-insulin-dependent diabetic mice. AB - 1. When carteolol, a beta-adrenergic blocker, was administered to KK-Ay/Ta Jc1 mice that are obese and develop spontaneously non-insulin dependent diabetes, their increase in bodyweight was arrested from the age of 16 weeks. Since their intake of food and water was not influenced by carteolol treatment, compared with the control KK-Ay/Ta Jc1 mice, abolition of the weight gain might be attributed to increased energy metabolism. 2. Non-fasting serum glucose levels in carteolol treated mice at the age of 17 weeks were within normal range (118 +/- 4 vs 186 +/ 12 mg/dL). An intraperitoneal glucose-tolerance test revealed that the carteolol treatment markedly restored glucose metabolism; fasting plasma glucose (88 +/- 6 mg/dL) was within normal range, and immunoreactive insulin (IRI; 5.8 +/- 0.8 vs 33.3 +/- 10.5 ng/mL) and plasma glucose levels at 60 min post glucose (361 +/- 44 vs 541 +/- 32 mg/dL) were significantly lower in carteolol-treated mice than those in the control group at the age of 20 weeks. 3. From these findings, carteolol is considered to have little effect on the growth of mice but to correct the obesity that develops after age 16 weeks, when their growth terminates. In addition, the normalization of blood glucose and marked decrease in IRI levels suggests that carteolol improves glucose tolerance by increasing the insulin sensitivity. 4. Since brown adipose tissue (BAT) is closely associated with thermogenesis and energy consumption, we tested whether carteolol may affect BAT.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7982279 TI - Sex differences in the parasympathetic nerve control of rat heart. AB - 1. As it has been shown that oestrogen enhances the cholinergic muscarinic activity in the central nervous system, we studied sex differences in the response to parasympathetic nervous stimulation in the rat heart using in vivo and in vitro preparations. 2. In in situ perfused, innervated hearts, stimulation of bilateral vagus nerves (15 Hz with 1 mumol/L physostigmine) inhibited sympathetic nerve stimulation (5 Hz) induced noradrenaline release to a greater extent in female than in male rats (54 +/- 5 vs 72 +/- 5% of control). Similarly, vagus nerve stimulation at 1-20 Hz reduced heart rate (HR) more in females than males, and this sex difference became more marked in the presence of physostigmine. The chronotropic effect of vagal stimulation was attenuated after ovariectomy but potentiated after castration when compared with sham-operated controls. In contrast, the muscarinic agonist methacholine reduced neural NA release and HR equally well in both sexes. 3. In anaesthetized rats, reduction in HR and mean arterial pressure by vagus nerve stimulation (1-20 Hz) was more pronounced in females than in males after inhibition of acetylcholinesterase with physostigmine. 4. The results indicate that activation of parasympathetic nerve leads to greater presynaptic and postsynaptic effects in female than in male rat hearts, presumably due to a higher level of acetylcholine release following nerve activation. PMID- 7982280 TI - Possible participation of NMDA and glycine receptors but not GABAA receptors in enflurane-induced opisthotonus in mice. AB - 1. We previously reported that volatile anaesthetics produce incidences of a transient opisthotonus in mice, a sign of CNS stimulation. This study was performed to investigate mechanisms by which enflurane-induced opisthotonus (EIO) occurs. 2. The effects of pretreatment of N-methyl-D-aspartate (NMDA) antagonists dizocilpine (MK-801; DIZ) and ketamine (KET), GABAA antagonists picrotoxin (PIC), pentylenetetrazol (PTZ) and glycine antagonist strychnine (STR) on the incidence of EIO were determined. Prior to exposure to 2.0% enflurane in air, male ddN mice were given intraperitoneal injections of 0.2 mL saline (control), 0.5-5.0 mg/kg DIZ, 20-80 mg/kg KET, 2.9 mg/kg PIC, 40.0 mg/kg PTZ and 0.75 mg/kg STR. After the injection, the behavioural state of the mice was observed for 20 min (the pre enflurane period). During the exposure to enflurane the time for immobilization, that is, anaesthetic induction time (IT), and the incidence of EIO were measured. 3. Dizocilpine (1.0-5.0 mg/kg) and KET (80 mg/kg) significantly (P < 0.01) reduced both the incidence of EIO and IT in a dose-dependent manner. During the pre-enflurane period DIZ produced incidences (5-40%) of transient seizures in a dose-dependent manner, while KET did not induce them at all. The two GABAA antagonists had no detectable effect on the EIO. Strychnine significantly enhanced the EIO. These CNS stimulants resulted in a 3-10% incidence of transient seizure and/or opisthotonus during the pre-enflurane period, but there was no correlation between DIZ-induced seizure and EIO. 4. These results suggest that the EIO is mediated by the NMDA and the STR-sensitive glycine receptors, but not the GABAA receptor.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7982281 TI - The effect of high perfusion rates on the endothelial diffusion barrier in rat mesenteric arteries in vitro. AB - 1. Arteries from Wistar-Kyoto rat mesenteries were cannulated with glass cannulae and perfused with Krebs' solution at controlled rates and distending pressure. Arterial diameter was measured and concentration-response curves generated with agonists applied via the perfusate (luminal) and via the solution bathing the outside of the preparation (extraluminal). 2. The alpha 1-adrenoceptor selective agonist methoxamine was about three times more potent when applied extraluminally than intraluminally in arteries perfused at either 25 or 500 microL/min, but the lipophilic alpha 1-adrenoceptor selective agonist SKF 89748-A was equally potent with either mode of application. 3. The extraluminal/intraluminal potency differentials for both methoxamine and noradrenaline were abolished by perfusion for 30 min at a rate calculated to give a high shear stress (100 dyn/cm2). 4. The potency of luminally applied acetylcholine was reduced less than two-fold by the high shear perfusion, and the ability of acetylcholine to maximally relax the arteries was unchanged. 5. It is concluded that (i) the endothelium of small arteries reduces the potency of luminally applied lipophobic agonists by acting as a diffusion barrier; (ii) the ability of the endothelium to act as a diffusion barrier is easily damaged by shear stress in vitro; and (iii) the ability of acetylcholine to relax arteries in vitro is a poor index of the full functioning of the endothelium. PMID- 7982282 TI - The control of human motor units. AB - 1. The motor unit, consisting of a single motor neuron and the skeletal muscle fibres that it innervates, is the final output pathway of the motor system. 2. Much is now known about the way that human motor neurons are recruited and controlled during voluntary and reflex movements. This review briefly summarizes some of the recent experimental data that has contributed to our present understanding. The review is largely limited to data obtained in human experiments. While much of what we know about the organization of the nervous system has come from studies of the anatomy and physiology of experimental animals, there are some questions that cannot be addressed in reduced animal preparations. The development of new techniques has made it possible to investigate the human nervous system at a level of detail that has not hitherto been possible. PMID- 7982283 TI - Rand Lecture, ASCEPT. GABA receptors: as complex as ABC? Australaisian Society for Clinical and Experimental Pharmacologists and Toxicologists. AB - 1. Receptors for the inhibitory neurotransmitter GABA are currently classified pharmacologically into two major subtypes. 2. GABAA receptors are antagonized by the convulsant alkaloid bicuculline, and are insensitive to activation by the GABA analogue baclofen. GABAB receptors are insensitive to bicuculline and activated stereoselectively by baclofen. 3. There is increasing evidence for 'novel' GABA receptors that pharmacologically fall outside that defined by the GABAA/B classification. 4. GABA receptors insensitive to both baclofen and bicuculline have been described in the spinal cord, optic tectum, retina, cerebellum and hippocampus. In addition such novel GABA receptors may be widespread in insects and bacteria. These novel receptors have been given a variety of descriptions: GABAC, GABANANB (non-A, non-B) and GABA rho (cloned from retina). 5. cis-4-Aminocrotonic acid (CACA), a structural analogue of GABA in a folded conformation, is considered to be a selective agonist of the putative GABAC receptors. Tritiated CACA binds to cerebellar membranes in a GABA sensitive, baclofen-insensitive manner. It can be displaced only by relatively high concentrations of bicuculline. 6. Autoradiographic studies show pronounced differences in regional distribution between the binding of CACA, the GABAA agonist muscimol and the GABAB agonist baclofen. 7. Novel GABA receptors may represent important new pharmacological targets. PMID- 7982284 TI - Inhibitory effects of verapamil on [3H]-acetylcholine release in the central nervous system of Sprague-Dawley rats. AB - 1. The purpose of the present study was to investigate the effects of verapamil, a Ca2+ channel blocker, on acetylcholine (ACh) release in the CNS. 2. Striatal slices of rats, prelabelled with [3H]-ACh, were superfused with Krebs'-Ringer solution. The slices were stimulated by electrical pulses (1 Hz) or by an excitatory amino acid, L-glutamate and the effects of verapamil on the release of ACh were examined. 3. Electrical stimulation produced an increase in [3H]-ACh release from the striatal slices. Exposure of the slices to verapamil significantly inhibited the stimulation-evoked [3H]-ACh release. 4. An endogenous excitatory amino acid, L-glutamate, also elicited the release of [3H]-ACh. Verapamil significantly reduced the L-glutamate-induced release of [3H]-ACh and the inhibitory effect of verapamil was more pronounced in the presence of Mg2+ in the medium. 5. The results of the present study demonstrate that verapamil inhibited both electrically- and chemically-stimulated [3H]-ACh release from the rat striatum. The inhibition of cholinergic transmission by verapamil might be related to the central effect of the Ca2+ channel blocker. PMID- 7982285 TI - Effects of diltiazem on [3H]-acetylcholine release in rat central nervous system. AB - 1. In the present study, we examined the effects of a Ca2+ channel blocker, diltiazem, on [3H]-acetylcholine (ACh) release in the rat CNS. 2. Diltiazem inhibited the electrically stimulated [3H]-ACh release in a dose-related fashion striatal slices of Sprague-Dawley (SD) rats. The basal release of [3H]-ACh was not significantly affected by diltiazem except at a high concentration. 3. The stimulation-evoked [3H]-ACh release was not different between spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY) rats. 4. The inhibitory effect of diltiazem on the stimulation-evoked [3H]-ACh release was significantly greater in SHR than in WKY rats. 5. The results show that diltiazem inhibited the stimulation-evoked ACh release in the rat CNS. The pronounced effect of diltiazem in SHR suggests that the inhibition of central cholinergic activity might contribute, at least partially, to the hypotensive mechanisms of the Ca2+ channel blocker. PMID- 7982286 TI - Heterogenous activity of BRL 35135, a beta 3-adrenoceptor agonist, in thermogenesis and increased blood flow in brown adipose tissue in anaesthetized rats. AB - 1. The effects of BRL 35135, a beta 3-adrenergic agonist, on body temperature and regional blood flow in brown adipose tissue (BAT) were simultaneously recorded in anaesthetized rats and compared to isoproterenol. 2. BRL 35135 at doses of 0.1 and 1 micrograms/kg (i.v.) induced dose-dependent increases in BAT temperature with minimal effects on systemic diastolic blood pressure (DBP), heart rate (HR) and BAT blood flow. 3. The thermogenic effect of BRL 35135 at a dose of 10 micrograms/kg (i.v.) was smaller than that at a dose of 1 microgram/kg, and was accompanied by a marked increase in BAT blood flow. 4. Isoproterenol at doses of 0.01-1 microgram/kg (i.v.) dose-dependently increased HR and BAT blood flow and decreased DBP. It did not affect BAT temperature. 5. These findings indicate that unlike isoproterenol, BRL 35135, at the lower doses, selectively causes thermogenesis in BAT which was detectable as changes in BAT temperature, and that the vasodilator effect in BAT is not as sensitive as the thermogenic effect of beta 3-adrenergic agonists. PMID- 7982287 TI - Differential control of vascular tone and heart rate by different amino acid neurotransmitters in the rostral ventrolateral medulla of the rat. AB - 1. To test the hypothesis that a central mechanism may play a role in the minimal reflex tachycardia noted in response to peripheral converting enzyme inhibition, we compared the effects of intravenous (i.v.) ceronapril (CER) with nitroglycerin (NTG) on neurotransmitter release in the rostral ventrolateral medulla (RVLM), using an in vivo microdialysis method in pentobarbital anaesthetized rats. 2. CER (0.1 mg/kg, i.v.) caused a progressive decrease in glutamate (GLU) release (CER 65 +/- 7% vs NTG 83 +/- 3% of each baseline at 140 min, P < 0.05) and attenuated the increase in glycine (GLY) release (CER 100 +/- 8% vs NTG 122 +/- 9%, P < 0.05). 3. Prevention of blood pressure reduction due to i.v. CER by concomitant infusion of a subpressor dose of angiotensin II (AII) attenuated the progressive reduction of GLU release (87 +/- 4%, P < 0.05 compared with NTG group), whereas GLY release was not affected (106 +/- 5%, NS compared with NTG group). 4. Perfusion of GLU into this area at approximately physiological concentrations resulted in a sustained tachycardia with an attenuation of the depressor effect of i.v. CER and perfusion of GLY solely lowered blood pressure. 5. These results demonstrate that i.v. converting enzyme inhibitor reduces the release of GLU in the RVLM, which was specifically caused by reducing circulating AII, without any effect on GLY release, thus resulting in the reduction of blood pressure with minimal effect on the heart rate. PMID- 7982288 TI - Blockade by intravenous losartan of AT1 angiotensin II receptors in rat brain, kidney and adrenals demonstrated by in vitro autoradiography. AB - 1. The in vivo inhibition of angiotensin II (AII) receptor binding in the rat brain, kidney and adrenal was investigated after intravenous administration of the AT1-selective AII receptor antagonist losartan. 2. Male Sprague-Dawley rats were administered intravenously either vehicle, or losartan at doses of 1, 3 or 10 mg/kg. Plasma samples were collected and tissues removed at 1, 2, 8 or 24 h after administration of the antagonist. The effects of losartan on AII receptor binding were assessed by quantitative in vitro autoradiography. 3. Losartan significantly increased plasma renin activity (PRA) by six-fold and nine-fold at doses of 1 and 10 mg/kg, respectively (P < 0.05). Plasma losartan concentrations rose from 0.83 micrograms/mL at 1 mg/kg to 46.5 micrograms/mL at 10 mg/kg 1 h after administration of the drug. Plasma renin activity returned to control, whilst losartan was undetectable 24 h after injection of the antagonist. 4. In the brain, losartan produced a dose-dependent inhibition of AII receptor binding to the brain structures which express exclusively, or predominantly, AT1 receptors both outside and within the blood brain barrier. By contrast, losartan did not affect binding to the nuclei which contain exclusively, or predominantly, AT2 receptors. 5. In the kidney, losartan blocked AII receptor binding to all anatomical sites in a dose-dependent manner. The inhibition peaked at 1 h and persisted beyond 24 h despite the fact that PRA had returned to control, and losartan was not detectable in the circulation. In the adrenal gland, where AT1 and AT2 receptors occur in both the cortex and medulla, losartan caused partial inhibition at both regions. 6. These results indicate that losartan, administered intravenously at these doses, and/or its active metabolites, partially penetrate the blood brain barrier to selectively inhibit central AT1 receptors, and exert selective and prolonged blockade at AT1 receptors in peripheral target tissues. PMID- 7982289 TI - In vitro incubation of bovine ovarian follicles: indications for an active and regulated renin-angiotensin system. AB - 1. The ovarian follicular renin-angiotensin system was investigated by using an in vitro incubation method, based on tissue incubation of individual bovine follicles. 2. Very high and varying concentrations of active renin (median 18.0 GU/kg, range 2.1-107 GU/kg; n = 101) and prorenin (11.7 GU/kg, range < 2.6-142 GU/kg; n = 101) existed in unincubated ovarian follicular tissue. 3. Active renin and prorenin increased 35 and 959%, respectively, in follicular wall tissue and incubation medium during 72 h of in vitro incubation. The protein synthesis inhibitor cyclohexamide inhibited active renin and prorenin formation. No activation of prorenin occurred in incubation medium or follicular fluid in vitro. Active renin was degraded during incubation. 4. Primarily prorenin but also active renin were secreted into the incubation medium. Secretion was directed both to the internal and external surface of the follicular wall. 5. Follicle-stimulating hormone (FSH) slightly stimulated the synthesis and secretion of prorenin in vitro. 6. The synthesis and secretion rates of active renin and prorenin varied markedly between individual follicles. 7. The finding of very high and varying concentrations of active renin in follicular wall tissues together with the formation and secretion of active renin during in vitro incubation provide further evidence for an active and regulated renin-angiotensin system in ovarian follicles. PMID- 7982290 TI - Blood volume measurements in the neonatal lamb: validation of a method using [51Cr]-labelled red cells. AB - 1. The reproducibility of blood volume measurements, using [51Cr]-labelled red blood cells (RBC) was tested in three lambs, 79-89 days of age, and the accuracy was tested in eight lambs, 83 +/- 0.4 days of age, in which blood volume was measured simultaneously by [51Cr]-RBC and [125I]-gamma globulin plus haematocrit (hct). 2. The blood volumes (mean +/- s.e.) of the three lambs, on four occasions, were 64.5 +/- 2.5, 68.8 +/- 2.9 and 63.9 +/- 3.7 mL/kg, respectively, and the coefficients of variation were 7.8, 8.6 and 11.6%, respectively. 3. The mean blood volume of eight lambs was 60.9 +/- 3.3 mL/kg by [51Cr]-RBC, and 60.8 +/- 2.4 mL/kg from plasma volume and hct. These were not statistically different. 4. Arterial hct was 31.2 +/- 0.5%, which was not statistically different from the whole body hct of 31.2 +/- 2.6%. 5. It is concluded that [51Cr]-RBC can be used to measure accurate and reproducible blood volumes in lambs. PMID- 7982291 TI - Analysis of polymorphic variation in drug metabolism: I. Kernal density estimation. AB - Kernel density estimation was examined as an objective, nonparametric approach to the detection of polymorphic variation in distributions containing multiple complex data sets. Power curves were constructed for the kernel density estimate based on its ability to detect worked bimodality in stimulated distributions as a function of the distribution size, the fraction contained within a particular subdistribution, and the location of the mean of that subdistribution with respect to the mean of the overall distribution. Comparisons were then made between kernel density estimation and the Kolmogorov-Smirnov test of maximal differences. Results showed that kernel density estimation performed as well or better than the Kolmogorov-Smirnov test and offered a number of advantages, including identification of the frequency and placement of individual modes and antimodes. The Kolmogorov-Smirnov test, on the other hand, examined normality of a distribution rather than modality or inherent polymorphism, and the outcome was highly dependent on the subdistribution location and total distribution size. We conclude that kernel density estimation is an excellent method for analysis of polymorphic variation in drug metabolism. PMID- 7982292 TI - Analysis of polymorphic variation in drug metabolism: II. Effects of data transformation on the sensitivity and specificity of modal detection. AB - Simulations were conducted for a model of drug metabolism involving 2 parallel competing pathways of elimination, wherein the effects of variability in 1 enzyme pathway were examined with respect to variability in recovery of its metabolite and recovery of metabolite through the second, nonvaried, co-eliminating route. Expression of metabolite recoveries as fractions of the total recoverable drug yielded a statistic possessing variability similar to the pattern of variability induced in the enzyme itself. However, the transformation was subject to a "distributive" effect, in that the magnitude of variation in the downstream metabolite was reduced and transferred through reciprocal variations in availability of unmetabolized drug to other nonvaried pathways. The sensitivity and specificity of the fractional recovery statistic were thereby diminished. Expression of recoveries as metabolic ratios, on the other hand, limited variability to the pathway in which it was originally induced. The pattern of variation was skewed and exaggerated, particularly towards the rightward, "poor metabolizer" tail of the distribution, and this caused problems with visual interpretations as well as more objective approaches like the kernel density estimate. Additional transformation to the log metabolic ratio provided considerable improvement in this regard. Thus, log metabolic ratios are the most sensitive and specific of the data transformations and are the preferred manner of expression in all multipathway metabolite analyses. PMID- 7982293 TI - Analysis of polymorphic variation in drug metabolism: III. Glucuronidation and sulfation of diflunisal in man. AB - The urinary excretion of diflunisal (D) and its metabolites diflunisal sulfate (DS), diflunisal phenolic glucuronide (DPG), and diflunisal acyl glucuronide (DAG) were measured in 110 healthy, drug-free Caucasian volunteers given 50 mg of diflunisal by mouth. When expressed as fractional recoveries, DS, DPG, and DAG were strongly negatively correlated with one another. Metabolic ratios, on the other hand, correlated positively and tended to localize variability within a single enzyme pathway. Thus, females using estrogen-containing oral contraceptives were shown to excrete 50% less DS and 20% more DAG than non-users, and recoveries of DS were reduced by about 30% in cigarette smokers. Kernel density analyses of the log metabolic ratios of DS and DPG were broad-based and unimodal. However, kernel density estimates of the distribution of log metabolic ratios of DAG showed 3 peaks, 1 of which (an extensive metabolizer polymorph) could be removed by excluding contraceptive-using females. Similarly, there were 2 poor metabolizer peaks in the distribution of log metabolic ratios of DS attributable to cigarette smoking and, in females, use of an oral contraceptive. Thus, we conclude that the metabolism of diflunisal is altered by cigarette smoking and oral contraceptives, and that kernel density estimation, as applied to log metabolic ratios, is a sensitive and specific method for detection of polymorphic variation in drug metabolism. PMID- 7982294 TI - Variations in strength of the porcine aorta as a function of location. AB - Dissecting aneurysms split the wall of the aorta and other large arteries to create a false lumen in parallel with the true lumen. Experiments were designed to determine the pressure required to tear the media and the work required per unit area to propagate the dissection once it started. India ink was injected into the media of 17 opened porcine aortas through a needle inserted parallel to the lumen of opened aortas placed in a saline bath. The ink was infused at 0.9 ml/min with a constant infusion pump as the pressure was monitored with a pressure transducer. The size of the bleb formed by the ink in the media was recorded with a video camera mounted perpendicular to the lumenal surface. All data were recorded on a computer. The pressure-volume curve was used to obtain the distensibility of the media (the upslope), the peak pressure, the tearing pressure, and the work of dissection (the area under the P-V curve once tearing occurred). The projected area of the bleb was calculated from the video images, and the work/area was calculated. The peak pressures were always extremely high, and ranged from 634 +/- 204 (SD) mmHg for the lower abdominal aorta to 816 +/- 145 mmHg for the lower thoracic aorta. The work/area ranged from 1.88 +/- 0.89 mJ/cm2 for the upper abdominal aorta to 11.34 +/- 4.05 mJ/cm2 for the lower abdominal aorta. An ANOVA showed that the lower abdominal aorta tore at lower pressures initially, but required much more energy to propagate the dissection. We believe that this is because of structural differences in the elastin pattern in the abdominal aorta. PMID- 7982295 TI - Effects of antihypertensive drugs on flow disturbances: nifedipine, captopril, and metoprolol evaluated by quantitative spectral analysis of Doppler flow patterns in patients with carotid stenosis. AB - Hemodynamic theories of atherogenesis suggest that flow disturbances (departures from laminar flow including high and low shear) and increases in heart rate may be important in the initiation, progression, and complications of atherosclerosis such as dissection and embolism. It is therefore desirable to evaluate the effects of antihypertensive drugs on the occurrence of such flow disturbances. Effects of metoprolol, nifedipine, and captopril were studied, by quantitative spectral analysis, in 20 patients with carotid stenosis to evaluate 3 indices of disturbed flow: peak velocity, spectral broadening index and window index (WI). Heart rate (HR), and the product of WI by HR, were improved (reduced) significantly by metoprolol (p < 0.05), and worsened by nifedipine (p < 0.05), but most of the effect was due to effects on heart rate. These findings suggest that most of the benefit of antihypertensive drugs on flow disturbances can be identified by counting heart rate. Further developments will require improved methods for quantitation of flow disturbances. PMID- 7982296 TI - Assuring the affordability of Canada's health care system. AB - Canada's health care system is challenged by a crisis of affordability. A sluggish economy and substantial federal, provincial, and territorial debt have caused health care spending, in spite of a good record of cost control, to consume nearly 10% of Canada's gross domestic product, largely due to a denominator effect. Issues identified as warranting further investigation as potential approaches to further reducing cost in order to match available resources include therapeutic effectiveness, drug use, hospital utilization, manpower planning, consumer access, and population approaches to improving health status. An important role exists for clinical investigators to contribute to health care reform. PMID- 7982297 TI - Can our health services be saved by technology evaluation? The Quebec experience. AB - The finances to support our health services at their present level are lacking, and much of the shortage is due to new health technologies. Through the utilisation of technology assessment (TA), it is hoped that we may be able to eliminate useless technologies and that the money so saved will allow us to maintain our health care services intact. Such hopes are exaggerated. The uses and limitations of TA are reviewed in the light of recent experience gained with the Conseil d'evaluation des technologies du Quebec. Technology assessment has only limited value in exposing ineffective technologies. More often, it can illuminate inappropriate use of technologies. However, its real value lies elsewhere, namely in making difficult choices between different technologies. An example is the choice between expensive, low osmolar contrast media in radiology and the cheaper, high osmolar material which causes more frequent reactions. Credible estimates of how much benefit will result from the commitment of how many extra dollars can facilitate such decisions. However, the user must clearly understand the limitations of cost-effectiveness estimates, which should never be used for policy purposes without full knowledge of all the qualifiers on which the estimates depend. PMID- 7982298 TI - The professional perspective--why get involved? AB - Four myths threaten Canadian medical education and the health care system. These myths are: (1) that health care costs are out of control; (2) that physicians can stimulate demand for health services; (3) that health research is a nicety; and (4) that health is an externality to considerations of economic policy. These myths tend to focus current concerns on sustainability, rather than on the ideal of continuous improvement. Comparative examinations reveal that Canadian health care spending is not out of line with that in other developed countries and suggest relative efficiency in the Canadian health care system. A broad and introspective approach to medicine is required that can critically address diverse issues such as variance in clinical practice patterns and the impact of poverty and unemployment. If health care educators can enshrine this approach in medical schools, professional medicine will be able to respond to the changing needs of Canadian society. PMID- 7982299 TI - Clinical implications of genetic and acquired defects in catecholamine synthesis and metabolism. AB - All major enzymes involved in catecholamine synthesis and metabolism have been cloned. In addition to some genetic defects of these enzymes responsible for well defined clinical syndromes, several enzymatic abnormalities may be due to environmental (e.g. pharmacological and nutritional) or biological (e.g. aging) factors, which may modify genome expression. The enzymes involved in catecholamine metabolism either lead to metabolites which cannot be reconverted to the parent catecholamine (such as products of monoamine oxidation and catechol O-methylation), or metabolites, which can be reconverted to the free catecholamine from which they are generated (such as products of sulfoconjugation). Reversible sulfoconjugation is partly regulated by the recently cloned enzyme, sulfatase. The importance of this reversible step is that it reconverts inactive into biologically active catecholamines. The balance of the sulfoconjugation-deconjugation interplay may have physiological implications; in addition to catecholamine release, it may determine the availability of free catecholamines during diurnal rhythms and stress or modify their renal excretion. Circumstantial evidence, including a close homology within the aryl sulfatases and steroid sulfatase gene, the first implicated in catecholamine metabolism, the second in steroid metabolism, suggests a genetic defect of sulfatases in essential hypertension. A similar, but secondary, sulfatase defect may affect catecholamine metabolism and action in chronic renal failure. PMID- 7982300 TI - Molecular interaction between cAMP and calcium in calmodulin-dependent cyclic nucleotide phosphodiesterase system. AB - The second messenger molecules cAMP and Ca2+ regulate a large number of eukaryotic cellular events. cAMP acts on protein kinases, and Ca2+ works through a ubiquitous calcium-binding protein, calmodulin. The 2 systems are not independent, however, but interact in several important fashions. These interactions can be demonstrated by calmodulin-dependent phosphodiesterase. The bovine heart calmodulin-dependent phosphodiesterase can be phosphorylated by cAMP dependent protein kinase, resulting in a decrease in the enzyme's affinity for calmodulin. The phosphorylation of calmodulin-dependent phosphodiesterase is blocked by Ca2+ and calmodulin, and reversed by the calmodulin-dependent phosphatase (calcineurin). The dephosphorylation is accompanied by an increase in the affinity of the phosphodiesterase for calmodulin. Results from this study suggest that the activity of this phosphodiesterase is precisely regulated by cross-talk between Ca2+ and cAMP signalling pathways. PMID- 7982301 TI - The future of clinical investigators and of academic medicine in Canada. AB - Health is part of our own personal well-being, as well as that of the community and of our nation: clinician-investigators lead us forward in new medical developments, and may even be of assistance in developing innovative programs of cost control and outcome analysis. Canada now devotes close to 10% of its gross national product to health expenditures, second only to the United States, and yet there is still the widespread perception within this country that "there is not enough." The issues are how to do more with less, and how to recruit more clinician-investigators from the diminishing pool of potential recruitees. Academic medicine, with its research focus, is well-suited to bring together newer perspectives of education and health, and these clinician-investigators may improve major areas of our health care partnership. PMID- 7982302 TI - Dark clouds over academic medicine, cornerstone of our health care system. PMID- 7982303 TI - Canadian Association of Medical Microbiologists in health research. PMID- 7982304 TI - Founder's Award of distinction in medical microbiology. PMID- 7982305 TI - Gallium-67 scintigraphy as an aid in the detection of spinal epidural abscess. AB - Gadolinium-enhanced MRI is considered the study of choice for diagnosing spinal epidural abscess (SEA). Most of such cases, however, are not suspected initially, and thus do not benefit from the procedure. A case of SEA is described in which positive Ga-67 scintigraphy shortly before onset of lower extremity dysfunction was instrumental in obtaining an emergency gadolinium-enhanced MRI and establishing the diagnosis. PMID- 7982306 TI - Quantification of gallium-57 citrate in breast milk. AB - A woman, 6 months postpartum and nursing her child, had a Ga-67 scintigram. A sample of breast milk obtained at day 2 revealed 2.8% of the injected dose (ID) per liter. The percent ID/L was compared with literature values; the highest concentration was in a report of galactorrhea. Similarity of the gallate ion to phosphate, as a possible explanation for accumulation in the breast, was pointed out. An earlier recommendation that a patient given Ga-67 citrate should discontinue breast feeding for at least 2 weeks was re-examined. PMID- 7982307 TI - The usefulness of gated blood pool imaging in the differential diagnosis of an intrathoracic mass. PMID- 7982308 TI - Rapid reversal of bone scan abnormalities in a patient with type 1 primary hyperoxaluria and oxalosis. AB - Serial bone scanning was performed on a 23-year-old man with type 1 primary hyperoxaluria, renal failure, oxalosis, and cardiac failure. The initial bone scan (6/22/90) demonstrated diffuse increased uptake in the axial and peripheral skeleton, heart, and the soft tissues of the lower extremities. A combined liver and kidney transplant was successfully performed with subsequent resolution of the oxalosis, renal failure, and cardiac failure. A follow-up bone scan (9/24/90) demonstrated resolution of abnormal heart and soft tissue uptake, as well as decreased uptake in the long bones. This case demonstrates that bone scanning may be a useful tool in the management of patients with oxalosis. The scintigraphic findings closely paralleled the clinical response to treatment of the disease and suggested decreased total body stores of calcium oxalate. PMID- 7982309 TI - Casual discovery of Tc-99m MDP uptake for melanoma metastasis in soft tissue. AB - The authors report the casual discovery in 1991 of a metastasis during Tc-99m MDP imaging of a 57-year-old woman who underwent surgery in 1983 for cutaneous melanoma on the right calf. The scan did not show bone alterations but did reveal an area of hyperactive uptake in the soft tissue of the medial surface of the thigh, where slightly altered pigmentation was also apparent. A subsequent immunoscan with Tc-99m-F(ab')2 225.28S confirmed increased uptake at this site. The lesion was removed and was histologically diagnosed as a skin metastasis from melanoma. Inguinal adenopathy appeared 6 months later. The uptake of Tc-99m MDP by both primary and metastases tumors has been described, although this may be the first report concerning melanoma. The uptake mechanism is not known. PMID- 7982310 TI - Management of thyroid papillary carcinoma with radioiodine in a patient with end stage renal disease on hemodialysis. AB - Metastatic papillary carcinoma was diagnosed in a 42-year-old woman. The cancer had invaded out of the gland and was present in many lymph nodes. After her surgical procedure, she was advised to have radioiodine. However, the patient had total renal failure and was on dialysis. Studies were carried out using a tracer dose of 2 mCi of radioiodine, demonstrating that approximately 60% of the radioactivity in the body was removed with each dialysis. Calculations indicated that a meaningful dose of radiation could be delivered to residual thyroid and metastases with 100 mCi of radioiodine and the total body radiation would be < 100 rad delivered over several days. Based on these analyses, she received 100 mCi of I-131 on two separate occasions and on follow-up scan, clinical evaluation and thyroglobulin measurement is free of disease. PMID- 7982311 TI - Relevance of Tc-99m DMSA scintigraphy in renal transplant parenchymal imaging. AB - Tc-99m DMSA renal scintigraphy was performed in 40 renal grafts. Cyclosporin A and glucocorticoids were given to all patients as antirejection therapy, and 11 also were given azathioprine. The kidneys were transplanted 1 to 97 months before the investigation. Seventy percent of kidneys had diffusely altered distribution of Tc-99m DMSA, and 43% had focal clear-cut parenchymal defects. The frequency of parenchymal defects observed on the DMSA scans was higher in patients who suffered manifest acute rejection episodes (8/16 versus 9/24 patients, borderline significance, P < 0.06), but had no relation to the living or cadaveric donor transplant or its function. A combination of peritubular edema and interstitial fibrosis is considered the most probable explanation of diffuse changes. The high frequency of clear-cut parenchymal defects most likely results from symptomatic or asymptomatic rejection episodes complicated by renal transplant infarcts. PMID- 7982312 TI - Brain perfusion SPECT in a patient with a subtle venous angioma. AB - Brain SPECT of regional cerebral blood flow using I-123 IMP demonstrated a focally decreased perfusion area immediately adjacent to a venous angioma in a patient with simple partial seizures. A positive correlation was obtained among the location of the venous angioma, the decreased perfusion area on SPECT images, and the electroencephalographic focus. Anomalous venous drainage through a venous angioma may explain a perfusion disturbance in the surrounding brain of the angioma. High-resolution SPECT imaging with magnetic resonance guidance provides useful information on the pathophysiology of venous angiomas. PMID- 7982313 TI - Brain SPECT artifact in multidetector SPECT system. AB - Stringent quality control cannot be overemphasized in performing SPECT. SPECT artifacts related to camera uniformity, center of rotation, and the patient's motion are well recognized. In this communication, another rare cause of a SPECT artifact related to a triad system is reported. A triple-headed SPECT system was accidentally equipped with two ultrahigh-resolution collimators and a general all purpose collimator during a brain SPECT study, causing a false cerebral blood flow defect. PMID- 7982314 TI - Intracystic administration of Tc-99m colloid particles to study retention and drainage in lymphangioma of the neck. AB - The particular use of lymphoscintigraphy to document retention and drainage in cystic lymphangioma of the neck is reported. Radionuclide examination using Tc 99m colliod particles, performed before sclerosing treatment with tetracycline in a patient with a large lymphangioma located in the neck, demonstrated a satisfactory tumor retention and slow outflow, enabling the administration of tetracycline without (risk of) organ toxicity. The treatment was successfully performed. PMID- 7982315 TI - Gastric emptying patterns in Kaposi's sarcoma and gastroenteritis secondary to human immunodeficiency virus infection. AB - The study included 11 patients with AIDS who underwent gastric emptying studies for solid food, endoscopy (esophagogastroduodenoscopy), and gastric biopsy whenever gastritis was diagnosed on endoscopy. All studies were performed within 1 week. The studies were retrospectively reviewed to analyze the changes in gastric emptying secondary to Kaposi's sarcoma (KS) with or without opportunistic infections. Two patients with KS only had rapid gastric emptying (T1/2 6.7 and 45 minutes). Two other patients with KS and opportunistic infections had normal gastric emptying (T1/2 56.7 and 70 minutes), and one patient with KS and opportunistic infections had rapid gastric emptying (T1/2 25.9 minutes). Four patients with gastritis secondary to opportunistic infections and no KS had delayed gastric emptying (T1/2 622, 92, 266.5, and 179.4 minutes). The remaining two patients had endoscopy showing gastritis not proven by biopsy, and both had rapid gastric emptying. One patient had gastric ulcer (T1/2 39 minutes), and the other had chronic active hepatitis and early cirrhosis (T1/2 15 minutes). Esophagitis was present in 6 out of 7 patients who had gastritis. Esophageal candidiasis was confirmed in three patients, and cytomegalovirus was confirmed in one patient. The findings suggest that gastroduodenal KS is associated with fast gastric emptying in patients with AIDS. However, normal gastric emptying study does not reflect normal gastric physiology in patients with AIDS. PMID- 7982316 TI - Scintigraphic evaluation of bile dynamics before and after endoscopic sphincterotomy. AB - Endoscopic sphincterotomy has been used for the treatment of many biliary disorders, including extraction of obstructing common bile duct stones. Manometric studies of the sphincter of Oddi and the common bile duct have shown a marked decrease in biliary tract pressures after sphincterotomy. A prospective study of 12 patients with intact gallbladders using hepatobiliary imaging before and after sphincterotomy was performed to assess changes in bile dynamics. Nonfilling of the gallbladder occurred in 9 of the 12 patients after sphincterotomy, indicating significant alteration of bile flow. Such changes in bile dynamics may have serious implications in patients selected for medical dissolution of gallstones. It may also adversely affect specificity of cholescintigraphy in diagnosing acute cholecystitis. PMID- 7982317 TI - Clinical signs and symptoms in pulmonary embolism. A reassessment. AB - The clinical diagnosis of pulmonary embolism (PE) remains difficult despite years of investigation. The clinical signs and symptoms of pulmonary embolism are numerous, but they are not diagnostically accurate. Radionuclide ventilation perfusion imaging (VQ) has become an important adjunct in screening patients for suspected PE. This study re-evaluates the predictive capabilities of various clinical signs and symptoms in a population of patients in whom angiography was thought to be necessary because of clinical concern for PE. One hundred one patients with suspected PE were retrospectively identified. Clinical information on them was complete, and laboratory studies, VQ imaging, and pulmonary angiography were performed. Thirty-seven clinical signs, symptoms, and other characteristics were individually compared for patients whose angiographic results were positive or negative for PE. Modifying or interactive effects on PE were then examined with logistic regression analysis. Several clinical conditions, including immobilization and recent surgery, were significantly associated with PE. Shortness of breath and history of smoking were significantly associated with negative results on pulmonary angiography. A "high probability" VQ scan was highly predictive (P < .0001) of positive results on angiography. When interactive factors for PE were examined, lack of shortness of breath and arterial pH < or = 7.45, lack of shortness of breath and respiratory rate > 23, diaphoresis in a nonsmoker and immobilized female, were significantly associated with PE. This study again documents the difficulty in using clinical criteria- including signs, symptoms, and laboratory determinations--to predict PE accurately, even in a population in which PE was of clinical concern irrespective of the VQ scan results.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7982318 TI - Esophageal transit of liquid in chronic alcoholism in patients with cirrhosis. Influence of esophageal varices. AB - Disturbances of esophageal motility are often encountered in chronic alcoholism, and numerous physiopathologic mechanisms responsible for this alteration have been documented. The exact role of esophageal varices, however, in inducing esophageal transit abnormalities remains unclear. In this study using scintigraphy, the authors studied esophageal transit in a large number of patients with cirrhosis to assess the direct effect of esophageal varices. Esophageal transit was found altered in 58 out of 141 patients with cirrhosis (41.1%). It was prolonged in 47.3% of patients with esophageal varices and in 29.2% of patients without varices (P < 0.05). The frequency of esophageal transit alteration was also related to the Child-Turcotte-Pugh (CTP) score, an index of the severity of liver disease (P < 0.01). The relationship between CTP class and transit alteration remained statistically significant in the group of patients with esophageal varices (P < 0.05). Conversely, when patients in each CTP class were analyzed separately, the frequency of esophageal transit abnormalities was not different in patients with and without esophageal varices. These results suggest that the severity of cirrhosis, rather than the presence of esophageal varices, constitutes the major factor in inducing esophageal transit alteration in patients with cirrhosis. PMID- 7982319 TI - Influence of age, gender, and ethnicity on nasal mucociliary clearance function. AB - Nasal mucociliary clearance functions were measured in 46 healthy Chinese adult subjects (21 women and 25 men; age range, 27 to 75 years). A single droplet of Tc 99m MAA was placed on the floor of the nasal meatus about 1 cm behind the mucocutaneous junction, and its course was followed with a gamma camera. The nasal mucociliary clearance function was presented as the velocity (mm/minute) of nasal mucociliary transport of the Tc-99m MAA droplet. The results showed the velocity to be 4.42 +/- 2.12 mm/minute (4.61 +/- 2.37 mm/minute in the right nostril; 4.24 +/- 1.83 mm/minute in the left nostril). When the patients were grouped according to age or gender the velocity was 4.8 +/- 1.9 mm/minute (right nostril), 4.4 +/- 1.9 mm/minute (left nostril) in the older subjects (60 years and older), and 4.4 +/- 2.7 mm/minute (right nostril), 4.1 +/- 1.8 mm/minute (left nostril). In the younger subjects (59 years old and younger) (P > 0.05) the velocity was 5.0 +/- 2.7 mm/minute (right nostril), 4.3 +/- 1.8 mm/minute (left nostril) in men and 4.1 +/- 2.0 mm/minute (right nostril), 4.2 +/- 2.0 mm/minute (left nostril), in women (P > 0.05). The authors concluded that the influence of age or gender on healthy Chinese adults is not apparent. In addition, the velocity of flow in Chinese adults is slower than those in other previously reported ethnic studies. PMID- 7982320 TI - Altered biodistribution of Tc-99m HMDP on bone scintigraphy from recent intravenous iron therapy. PMID- 7982321 TI - An early false-negative bone scan in a spiral fracture. PMID- 7982322 TI - Gallium scintigraphy in the tumor stage of mycosis fungoides. PMID- 7982323 TI - Tl-201 chloride bone marrow uptake in a patient with minor thalassemia. PMID- 7982324 TI - Early detection of tuberous sclerosis by I-123 IMP SPECT in a neonate. PMID- 7982325 TI - Unilateral absent lung perfusion in Marfan's syndrome. PMID- 7982326 TI - Vertebral body hemangioma showing increased uptake of Tc-99m MDP and decreased Tc 99m labeled red blood cells. PMID- 7982327 TI - Therapeutic radioiodine interference with subsequent diagnostic imaging. PMID- 7982328 TI - Legg-Perthes disease: partial or total loss of femoral head? Contribution of SPECT images. PMID- 7982329 TI - Nonvisualized kidney on bone scintigraphy due to a depressed diaphragm. PMID- 7982330 TI - Drug transfer across the placenta. Considerations in treatment and research. AB - Using the pregnant woman as a means to medicate her fetus represents a new and exciting therapeutic approach in clinical pharmacology. In years to come, we will see an increase in the use of the currently accepted fetal therapies and an increase in the number of therapies available to the caregiver or clinician aimed at assisting the unborn child. The pharmacologist, through in vitro research that aids our understanding of the role of the placenta in fetal drug therapy, can contribute to the growth of this new field within the realm of obstetric medicine. PMID- 7982331 TI - Prevention of neural tube defects with periconceptional folic acid. AB - A body of convincing evidence demonstrates that periconceptional folic acid supplements are associated with a reduction in the risk for first occurrences of neural tube defect and for recurrence of neural tube defects among women with a previously affected pregnancy. The mechanism(s) of this protective effect are unknown, and although the effect can be seen with folate doses between 0.4 and 4 mg, the optimal dose remains unknown. The optimal method of ensuring that all women of child-bearing age receive this dose of folate remains in question; supplementation offers the advantage of targeting only the population at risk, whereas food fortification offers the advantage of ensuring compliance in virtually all of the population at risk. The use of periconceptional folic acid can be expected to reduce, but not abolish, the incidence of neural tube defects. Research into the mechanism(s) of the protective effects of folic acid and the underlying biology of neural tube defects is required to address the problem of how to develop therapeutic strategies to further reduce the impact of neural tube defects. PMID- 7982332 TI - Prevention of intraventricular hemorrhage in the premature infant. AB - PIVH remains a significant problem in the care of the preterm infant. Recent technologic advances such as real-time ultrasonography and Doppler flow studies have facilitated accurate diagnosis and provided insight into the pathogenesis. Although the overall incidence of PIVH is declining, the outcome of survivors of PIVH--especially those with more severe grades--remains unfavorable. Several antenatal and postnatal interventions aimed at reducing the overall incidence and severity of PIVH have been attempted. Antenatal interventions, in particular phenobarbital, appear to be promising because a substantial percentage of PIVH occurs in the immediate perinatal period. It is significant that the four reported antenatal phenobarbital trials demonstrated a consistent decrease in severe PIVH. Despite the fact that these studies have different designs and each must be considered on its own, the consistency of results makes a strong statement regarding efficacy and safety. The on-going multicenter Neonatal Network trial should provide definitive results as to the efficacy and safety of antenatal phenobarbital in the prevention of PIVH. PMID- 7982333 TI - Pharmacologic enhancement of fetal lung maturation. AB - During the 22 years since the first clinical reports of prenatal corticosteroid treatment to enhance fetal lung maturation, this treatment has been studied in thousands of preterm newborns. These studies demonstrated that prenatal steroid treatment reduces RDS among premature newborns at 26 to 33 weeks gestation. The potent fluorinated steroids, betamethasone and dexamethasone, are more effective in accelerating lung maturation than are the less potent corticosteroids, cortisol, cortisone, and prednisone. No immediate or long-term adverse effects have been demonstrated for the newborn or fetus. With PROM, mothers may have an increased risk of endometritis without a clear increase in overall frequency of infection, at the same time steroids significantly decrease the frequency of RDS in the newborns. During these 22 years of evaluation and application of prenatal steroid treatment to reduce RDS, the survival of the very low birth weight (< 1501 g) newborn has increased dramatically. Major morbidities, however, impact significantly on the quality of life for these survivors with birth weights as low as 500 g and gestations as short as 22 to 23 weeks. Prenatal steroid treatment reduces the frequency of PDA, intraventricular hemorrhage, NEC, and bronchopulmonary dysplasia. These are the most important and frequent morbidities that reduce the quality of life for the very low birth weight survivor. Without clearly demonstrable and major adverse effects for the mother or child from corticosteroid treatment, the cost/benefit ratio strongly and clearly favors treatment when preterm delivery is anticipated. Hopefully, obstetricians will use corticosteroids more often in the management of preterm labor because this treatment may markedly improve the quality of survival for many premature newborns. PMID- 7982334 TI - Drug therapy for fetal arrhythmias. AB - Diagnosis of specific types of fetal arrhythmias, especially tachyarrhythmias, is still difficult, often making semi-blind treatment inevitable. Published reports of many experienced clinicians show that digoxin remains a mainstream drug for therapy for fetal SVT and AF; digoxin is used as an initial monotherapy or in combination with other drugs if unresponsive to digoxin alone. It remains to be evaluated whether this treatment strategy offers overall better clinical outcomes than other approaches. Verapamil and propranolol are used in combination with digoxin, although successful control by propranolol seems rare. Quinidine and procainamide reportedly are effective in some cases. Reports on successful outcomes of flecainide therapy have emerged recently, although possible negative inotropic actions are of concern. Amiodarone is effective in some cases with incessant tachycardias, but risks of fetal thyroid dysfunction preclude its use as a firstline drug in uncomplicated fetal SVT cases. Empiric findings still prevail in the area of fetal drug therapy for arrhythmias, especially tachycardias. Heterogeniety of the conditions, lack of comparative studies, and difficulty in monitoring fetal drug level, let alone unbound drug concentrations, further complicate assessment of efficacy of different modes of treatment. Problems identified throughout this review have yet to be solved. Despite all these uncertain factors, however, it is clear that no one can undermine never ending efforts of many clinicians in this exciting field of medicine. PMID- 7982335 TI - Fetal blood transfusion. AB - The concept of transfusing the fetus in utero is simple, but its success demands an experienced, dedicated team, with excellent laboratory back-up. High resolution ultrasound has enabled us to sample fetal blood. This allows immediate, precise assessment and rational treatment of the anemic fetus, with improved outcome for all such fetuses and, particularly, for the hydropic, moribund group. Fetal blood transfusion programs should be concentrated in regional perinatal centers. PMID- 7982336 TI - Antenatal management of the thrombocytopenias. AB - Thrombocytopenia, the most common hemostatic disease of the newborn, can now be safely identified and treated antenatally to prevent life-threatening fetal and neonatal hemorrhage. This article focuses on the fetal thrombocytopenias with emphasis on the most common causes, the immune thrombocytopenias, including alloimmune and autoimmune mechanisms. The clinical presentation and differential diagnosis are discussed briefly. PMID- 7982337 TI - Treatment of polyhydramnios with indomethacin. AB - Polyhydramnios detected in a pregnancy should always be investigated thoroughly. We believe chromosomal abnormalities should be excluded, but that determination need not delay therapy. Indomethacin has been shown to reduce amniotic fluid volume in certain cases, but a strict monitoring schedule should be followed whenever it is administered. At our institution, we are investigating the effect on the fetus of newer, more selective prostaglandin synthetase inhibitors that should have beneficial effects similar to indomethacin, but be devoid of its unwanted side effects. PMID- 7982338 TI - Prenatal diagnosis and management of congenital adrenal hyperplasia. AB - Congenital adrenal hyperplasia is one of a few inherited disorders that can be managed by administering medication to the fetus via oral maternal administration. Dexamethasone given in the first trimester ameliorates genital ambiguity in the affected female fetus. Mother and fetus should be monitored during and after pregnancy for treatment-related complications. Therapy can be coordinated with prenatal diagnostic testing. PMID- 7982339 TI - Diagnosis and management of altered fetal thyroid status. AB - Recent advances in the understanding of the normal process of maturation of fetal thyroid function now make possible the in utero diagnosis of fetal system abnormalities. The approach to the fetus at risk for altered thyroid function is discussed in the context of normal thyroid development and emphasis is given to the fetus presenting with goiter. PMID- 7982340 TI - In utero vaccination. AB - It is estimated that 4 million children die each year of vaccine-preventable diseases and another 4 million are permanently disabled. Although vaccination is the most cost-effective health method, there is a discrepancy between our level of knowledge and practices applied. Vaccination of pregnant women provides the mother with antibodies that could be transferred across the placenta and provide the neonate with high antibody titers until active immunization is likely to be protective. The ability to provide such passive childhood immunization is beneficial and cost-effective, especially in developing countries where routine childhood immunization is not widely practiced. Further progress depends on the development of more efficient antigens, carrier proteins, and formulations of multiple-antigen vaccines. Further studies should determine the ideal timing for in utero vaccination to provide protective antibodies to the full-term infant and the premature infant. This ideally should be achieved without compromising the protective effect during the first months of life and without causing immune tolerance when given early in pregnancy. The future of in utero vaccination depends on continuing basic research, which should provide improved vaccines and clinical studies that demonstrate the safety and effectiveness of vaccination for both mothers and infants. Liability issues should be addressed and greater awareness of obstetricians, family physicians, and the general public should be achieved. PMID- 7982341 TI - Prevention, diagnosis, and treatment of fetal toxoplasmosis. AB - Despite the limitations, the available data lead to the conclusion that treatment of the mother may be of benefit to the fetus. To date, harmful effects of maternal therapy on the fetus have not been substantiated. Current recommendations for fetal therapy of toxoplasmosis include the initiation of spiramycin in the pregnant woman when acquired toxoplasmosis is strongly suspected in pregnancy. Prompt detection of infection in the mother is important in order to start therapy as early as possible. An attempt to determine the status of the fetus is undertaken by prenatal diagnostic procedures such as amniocentesis, cordocentesis, and ultrasonography. After confirmation of fetal infection, repeated courses of a combination of pyrimethamine, sulfadiazine, and folinic acid should be alternated with courses of spiramycin. If the fetus is not infected, spiramycin should be continued in repeated courses or throughout pregnancy. Pregnancy termination tends to be reserved for cases in whom ultrasonographic examination demonstrates the fetus to be severely affected. The importance of postnatal follow-up and treatment, although not addressed in this article, must be emphasized. The advent of fetal therapy offers hope that the problem of congenital toxoplasmosis will become less common. In addition to currently available options, the future may offer new avenues of therapy, such as the possibility of treating infected fetuses by the intra-amniotic infusion of drugs. PMID- 7982342 TI - Life-threatening asthma. AB - This article focuses on various issues related to acute, life-threatening episodes of asthma. The areas discussed include epidemiology, clinical assessment, pharmacologic treatment with bronchodilators and anti-inflammatory agents, endotracheal intubation, mechanical ventilation, adjunctive and nonconventional therapy used in the management of the mechanically ventilated asthmatic, and the prognosis of patients who require mechanical ventilation, including both short-term morbidity and long-term outlook. PMID- 7982343 TI - Emergent assessment and management of acute respiratory failure in COPD. AB - Acute respiratory failure in patients with COPD is a common cause of emergent medical intervention and can be difficult to assess and manage. Assessment is complicated by the imposition of acute respiratory failure on chronic respiratory failure and by the large number of problems that can tip a carefully compensated patient with COPD toward acute respiratory failure. Management must include correcting life-threatening hypoxemia and life-threatening acidosis, treating the underlying disease processes, and preventing and treating complications. Management can be enhanced by an understanding of the prognosis of acute respiratory failure in COPD and by incorporation of some ethical and societal issues. PMID- 7982344 TI - Acute cardiogenic pulmonary edema. AB - This article examines the pathophysiology, diagnosis, treatment, and outcome of acute cardiogenic pulmonary edema, as well as re-expansion, high-altitude, postobstructive, and neurogenic pulmonary edemas. Acute cardiogenic pulmonary edema most commonly presents as a consequence of congestive heart failure. The other important causes are acute myocardial dysfunction, documented myocardial infarction, postoperative cardiac dysfunction, and pulmonary hypertension. All these entities have in common increased pulmonary vascular pressures that lead to pulmonary edema. PMID- 7982345 TI - Diagnosis and management of acute lung injury. AB - Severe acute lung injury, also known as the adult respiratory distress syndrome (ARDS), is a dynamic and explosive clinical syndrome which exacts a mortality of approximately 50%. The criteria for the diagnosis of severe acute lung injury include five principal elements: hypoxemia despite high concentrations of supplemental oxygen, diffuse pulmonary infiltrates on chest radiographs, decreased lung compliance, appropriate antecedent history, and the absence of congestive heart failure. Identifying an appropriate antecedent history requires consideration of a diverse group of etiologies which may injure alveolar structures via either the air-lung or blood-lung interface. The management of patients with acute lung injury should be approached with four principal goals: (1) cardiopulmonary resuscitation and stabilization; (2) rapid identification and elimination of the cause of lung injury; (3) achieving adequate tissue oxygen delivery and support of other end-organs; and (4) prevention, recognition, and aggressive treatment of any complications that develop during the course of therapy. Recent observations have suggested that conventional methods of positive pressure ventilation may indirectly injure alveolar tissue, thereby perpetuating lung injury. Furthermore, the optimal use of fluid and hemodynamic support remains controversial. Thus, controlled clinical trials are necessary to develop oxygenation, ventilatory, and hemodynamic support strategies which optimize recovery and minimize further injury and to define the role of newer pharmacologic agents in the prevention and treatment of acute lung injury. PMID- 7982346 TI - Massive pulmonary embolism. AB - Massive pulmonary embolism remains a clinical challenge where rapid diagnosis and appropriate therapy have a critical impact on patient outcome. This article reviews the pathophysiology, diagnosis, and therapeutic options involved in the management of pulmonary embolism. Clinical case discussions illustrate the principles that are described by the authors. PMID- 7982347 TI - Unusual forms of pulmonary embolism. AB - The first word of the title, unusual, captures the theme of this article. The entities discussed here: fat embolism, tumor embolism, venous air embolism, and amniotic fluid embolism, as well as other unusual embolic events are uncommon disorders that occur in specific circumscribed clinical settings. We have attempted to provide a cognitive jolt to remind the reader to consider these unusual events in appropriate differential diagnoses. No laboratory test, physical finding, or patient complaint will yield a timely diagnosis. Yet, these entities can be acutely life threatening; swift recognition is imperative. Timely and effective therapy rests on the clinical certainty that a test is not likely to establish. It is, perhaps, the greatest demand placed upon the agile clinical mind--to think of it! PMID- 7982348 TI - Life-threatening pneumonia. AB - Severe pneumonia can be acquired by previously healthy patients, those with pre existing illness, or those hospitalized for an unrelated illness. Because diagnosis is frequently difficult or delayed, treatment is usually empirically tailored to the most probable offending organisms and the patient's condition. This article reviews the pathogenesis of community- and hospital-acquired pneumonia, clinical features, and diagnostic techniques. An approach to selecting an antibiotic regimen is suggested. PMID- 7982349 TI - Infant's transitions toward adult-like scanning. AB - Visual scanning patterns of 6-13-week-old infants are derived from some 50 half minute assessments in which the infants viewed static geometric figures. Measures include fixation dwell-times, saccade lengths, and the choices and sequences of saccadic targets. From the patterns of change across 3 age periods, it appears that as infants grow older an initial salience-guided scanning increasingly is replaced by volitional control over the choice of saccadic targets. The change tentatively is attributed to neural developments within later stages of the infant visual system. PMID- 7982350 TI - Imagery, action, and young children's spatial orientation: it's not being there that counts, it's what one has in mind. AB - Young children typically fail when asked to judge how objects would look if they moved or changed shape, and this has been taken to mean that they lack the competencies for dynamic imagery. We used a different approach to study young children's imagination and found evidence of much earlier competence. Across 6 experiments, people were asked to imagine familiar surroundings and anticipate their spatial orientation from different observation points there. In the first 2 experiments, children (2 1/2-9-year-olds) and their parents sat at home and were asked to call to mind knowledge of their (child's) classroom relative to the perspective at their (child's) seat at (pre)school. After this, subjects were asked to judge the perspective at the teacher's seat in each of 2 conditions. In the Locomotion Condition they were asked to imagine walking from their seat to the teacher's seat while physically walking a path that resembled the actual one in the remote classroom. In the Imagination-only Condition the instructions were the same but they were not accompanied with physical walking. Children 3 1/2 years of age and older, like the adults, were accurate and rapid in the Locomotion Condition. In the Imagination-only Condition the children almost never judged perspective correctly; the adults responded accurately but slowly. These findings were replicated and extended across 4 additional experiments designed to clarify the operating principles that link perceiving, imagining, and acting. PMID- 7982351 TI - Semantic constraints on word learning: proper names and adjectives. AB - 4 experiments examined 3- and 4-year-olds' interpretations of novel words applied to familial objects in the sentence frame, "This Y is X," where X is a novel word, and Y is a familiar basic-level count noun (e.g., "dog," "cup"). These novel words are ambiguous and could be interpreted either as proper names (e.g., "Fred") or as adjectives/mass nouns (e.g., "red"/"lead"). The experiments addressed 2 questions. First, do children appreciate that the words can be construed either as proper names referring to individuals or as adjectives/mass nouns referring to salient properties/material kinds? The results showed that children could easily make either interpretation. Second, what factors affect children's tendency to make either a proper name or an adjective/mass noun interpretation? In the experiments, children learned the novel words for a range of animals and artifacts. Most children who learned the words for typical pets (e.g., a bird) made proper name interpretations, as did the majority of those who learned the words for certain non-pet animals (e.g., a caterpillar) described as possessed by someone, but only about half of those who learned the words for such non-pet animals not so described. Very few children who learned the words for either simple (e.g., a shoe) or complex (e.g., a boat) artifacts made proper name interpretations. The results provide clear evidence of the role of semantic information in constraining children's interpretation of a novel word, and they help to refine an understanding of what counts as a nameable individual for preschoolers. PMID- 7982352 TI - What types of linguistic information do children use in spelling? The case of flaps. AB - We sought to determine what types of linguistic information children represent in their spelling by examining their performance on the flaps of words such as city and lady. In 4 experiments, children often misspelled flaps as d. This d bias was common until at least second grade, with few children showing a bias toward t. We found no evidence that children have an underlying representation of city as containing /t/, for children said such words with /d/ when speaking very slowly. Even kindergartners were more accurate at spelling the flaps of words such as dirty, which have a stem ending with /t/, than the flaps of words such as city. Thus, children use meaning relations among words to aid their spelling before they have formally been taught to do so. The results show that young children are not purely phonetic spellers as they are often portrayed. The results further suggest that phonology and orthography are closely related systems that interact during development. PMID- 7982353 TI - The development of memory and processing capacity. AB - The assumption of some developmental theories that short-term memory is the workspace of higher cognitive processes, and consequently that span measures processing capacity, is claimed to be inconsistent with the working memory literature. 4 experiments, using children aged 5 to 12 years, contrast this theory with a model in which short-term memory and the processing space component of working memory are at least partly distinct. Experiments 1 and 2 varied processing load, holding duration constant. The processing load manipulation had little effect on recall of a short-term memory preload. Experiments 3 and 4 failed to support the prediction that the greater processing efficiency of older children would be associated with slower loss of information from short-term memory. Although counting and rehearsal rates increased with age, and correlated with span, they did not predict the rate of loss of memory preload due to intervening counting. The data suggest that effects obtained with short-term memory span do not provide clear indications of overall working memory development, because short-term memory span and the processing space component of working memory entail distinct systems. PMID- 7982354 TI - Young children's understanding of "remember" and "forget". AB - 3 studies examined young children's understanding that if one "remembers" or "forgot," one must have known at a prior time. In Study 1, 4-year-olds but not 3 year-olds understood the prior knowledge component of "forgot"; both groups understood that a character with prior knowledge was "gonna remember." Study 2 controlled for the possibility that good performance on "remember" might be due to a simple association of remembering with knowledge. A significant number of 4 year-olds but not 3-year-olds understood that when 2 characters currently knew, the one with prior knowledge remembered, and that when neither character currently knew, the one with prior knowledge forgot. Study 3 made prior knowledge more salient by making the remembered or forgotten item visible to the subjects throughout. 4-year-olds performed near ceiling on both verbs, whereas 3-year olds' performance did not differ from chance. The results are discussed in relation to children's developing understanding of the mind. PMID- 7982355 TI - Indian and English children's understanding of the distinction between real and apparent emotion. AB - 24 preschool and 24 school-entry children in Bombay, India, and 24 preschool and 24 school-entry children in Oxford, England, were tested on their ability to distinguish between real and apparent emotion in response to stories involving child-adult and child-child interactions. Younger Indian girls did better than younger English girls, and the data reveal effects due to age, culture, gender, and story type which suggest a more social model of the understanding of emotion than has been proposed by other researchers using this methodology. PMID- 7982356 TI - On the relation between social information processing and socially competent behavior in early school-aged children. AB - This article tested the hypotheses that (1) children's behavioral competence is a function of patterns of social information processing; (2) processing correlates of behavior occur at each of 5 steps of processing within each of 3 social situations; (3) measures at each step uniquely increment each other in predicting behavior; (4) the relation between processing and behavior is stronger within than across domains; and (5) processing patterns are more sophisticated among older than younger children and the processing-behavior relation is stronger among older than younger children. Videorecorded stimuli were used to assess processing patterns (encoding, interpretational errors and bias, response generation, response evaluation, and enactment skill) in 3 domains (peer group entry, response to provocation, and response to authority directive) in 259 first , second-, and third-grade boys and girls (ages 6-9 years). Ratings of behavioral competence in each domain were made by peers and teachers. Findings generally supported hypotheses, with the magnitude of relations being modest. PMID- 7982357 TI - The development of affiliative and agonistic social patterns in differentially reared monkeys. AB - Bonnet macaques that had been reared from 3 to 6 months of age in experimental environments that appeared to adversely affect their ability to separate from mother to explore a novel physical environment in dyadic assessments shortly after the rearing experience were tested during late adolescence, an average of 2.5 years later, under conditions of increasing unfamiliarity and complexity of the social milieu. 6 monkeys, the low-foraging-demand (LFD) group, were reared by mothers having constant easy access to food during the experimental rearing period. Another 6 monkeys, the variable-foraging-demand (VFD) group, were reared by mothers having a foraging task that varied between easy and difficult in 2 week blocks during the experimental rearing period. Although no treatment group differences were evident during the initial rearing period, during subsequent social challenges VFD monkeys exhibited a diminished capacity for affiliative social engagement relative to LFD monkeys and were socially subordinate to LFD monkeys. PMID- 7982358 TI - Caring behavior in children of clinically depressed and well mothers. AB - Young children's sensitivity and responsiveness to mothers' needs were investigated under conditions of high and low parenting risk (depressed and nondepressed mothers, SADS-L). Child characteristics of gender, affect, and impulse control problems and the mother-child attachment relationship were examined as they related to children's caring actions. Children's caring behavior was observed in an experimental situation in which their mothers simulated sadness and in a naturalistic setting. Attachment alone and child's problems alone were not predictors, and maternal diagnosis alone was not a strong predictor. Girls were significantly more caring than boys. Severe maternal depression was necessary to bring out high levels of responding in boys. Highest frequencies of caring were from children with severely depressed mothers, problems of affect regulation, and secure attachment. The importance of recognizing interacting influences and diverse underlying processes in the development of children's caring behavior is discussed. PMID- 7982359 TI - Predicting behavior problems in children with epilepsy: child factors, disease factors, family stress, and child-mother interaction. AB - This study examines the relative role of parent-child relationships, family stress, and disease factors in predicting behavior problems in children with epilepsy. It extends existing literature on parent-child relationships and behavior problems by examining children with biological risk. Child-mother interaction was observed for 51 children with epilepsy ages 7-13 years and related to teacher- and parent-reported behavior problems. Child's self-reliance correlated with parent-reported problems; expression of affect related to teacher reported externalizing problems. A child self-reliance factor accounted for behavior problems after partialing age, gender, IQ, epilepsy variables, and family stress. The term child gender x quality of mother-child interaction predicted teacher-reported externalizing problems, with mother-child interaction correlated with behavior problems for boys. Child-parent relationships predict the development of behavior problems over and above the influence of disease related factors, even for children at considerable biological risk. PMID- 7982360 TI - Infant day-care, attachment, and the "file drawer problem". AB - The research literature on infant day-care and attachment may be biased by the unavailability of "file drawer" studies, unpublished data showing no statistically significant effects. Replication studies, whether showing an effect or not, are essential to clarify the relation between day-care and attachment. This study of 105 12-month-olds is an attempt to replicate four similar studies summarized and combined by Belsky to show that infants in day-care are at risk for insecure attachment. In the present study, no results were robust enough to emerge consistently, although there was a trend for more negative attachment outcomes to be associated with little or part-time day-care rather than with full time day-care. In general, the results suggest that the specific measures, definitions of full- and part-time, and statistical techniques used in studies examining the relation between day-care and attachment are likely to affect the outcome of such studies. PMID- 7982361 TI - Stability and transmission of attachment across three generations. AB - Stability of adult attachment and transmission of attachment across 3 generations were examined in a longitudinal study of 96 infants, mothers, and maternal grandmothers. The Adult Attachment Interview (AAI) was used to assess attachment in mothers (during pregnancy and when infants were 11 months old) and grandmothers (any time during the study). The Strange Situation (SS) was used to assess attachment in infants at 12 months. Both the 3- and 4-category classification systems of the AAI and SS were used. Mothers' AAI classifications were stable over 12 months in 90% (3-category) and 77% (4-category) of mothers. Mothers' AAI classifications during pregnancy predicted infants' SS classifications in 81% (3-category) and 68% (4-category) of cases, and grandmothers' AAI classifications in 75% (3-category) and 49% (4-category) of cases. Using log-linear analysis, we show that a simple parent-to-child model accounts for transmission of attachment. PMID- 7982362 TI - The influence of temperament and mothering on attachment and exploration: an experimental manipulation of sensitive responsiveness among lower-class mothers with irritable infants. AB - 6-month-old infants selected on irritability shortly after birth and their mothers were randomly assigned to 2 intervention and 2 control groups to test the hypothesis that enhancing maternal sensitive responsiveness will improve quality of mother-infant interaction, infant exploration, and attachment. The intervention lasted 3 months and ended when the child was 9 months of age. When infants were 9 months of age, intervention group mothers were significantly more responsive, stimulating, visually attentive, and controlling of their infant's behavior than control group mothers. Intervention infants had higher scores than control infants on sociability, self-soothing, and exploration, and they cried less. Quality of exploration also improved, with intervention infants engaged in cognitively sophisticated kinds of exploration more than control infants. At 12 months of age, significantly more intervention group dyads were securely attached than control group dyads. PMID- 7982363 TI - Infant temperament measured by multiple observations and mother report. AB - Observers and mothers rated infant behavior (n = 50) in the home on dimensions of temperament once a week for 8 weeks. Although week-to-week correlations were modest (intraclass correlations of .14-.36), aggregates of the 8 observations had high reliability for both observers and mothers. Mother reports were tied to our observation sessions by having mothers (a) rate their infants' behavior during the period when our observations were made and (b) use a questionnaire that mirrored the scoring system used for scoring the videotaped observation sessions. When direct observations were compared with mother reports (on the aggregated weekly reports and on 4 widely used questionnaires), little evidence of mother observer correspondence was found. The interpretation of the large literature that has used maternal report is discussed, as well as the importance of direct observation of infant behavior when temperament is assessed. PMID- 7982364 TI - Developmental change in infant cortisol and behavioral response to inoculation. AB - Infant cortisol and behavioral responses to receiving 1 versus 2 inoculations on 1 pediatric office visit were observed at 2 and 6 months of age. Cortisol level (pre- plus postinoculation level) decreased with age, whereas cortisol response (post- minus preinoculation level) did not vary with age when the data were aggregated over infants showing a pre- to postinoculation cortisol increase and those showing a decrease. Nonetheless, for those infants who showed a cortisol increase, cortisol level and response decreased with age. Infants quieted faster at the older age. There was a moderate relation between quieting behavior and cortisol response, at least for infants who showed a pre- to postinoculation cortisol increase. These findings indicate a developmental trend for a decline over age in adrenocortical reactivity to inoculation for infants showing a cortisol release following the perturbation. Results were comparable whether infants received 1 or 2 inoculations. PMID- 7982365 TI - Beyond the face: an empirical study of infant affective configurations of facial, vocal, gestural, and regulatory behaviors. AB - This article evaluates the extent to which infants' expressive modalities of face, gaze, voice, gesture, and posture form coherent affective configurations and whether these configurations are related to specific interactive contexts. 50 6-month-old infants and their mothers were videotaped in Tronick's Face-to-Face Still-Face Paradigm. The infants' gaze, voice, gestures, self-regulatory, and withdrawal behaviors were coded with the Infant Regulatory Scoring System (IRSS). The infants' facial expressions were coded with Izard's AFFEX system. Contingency analyses of IRSS behaviors and AFFEX expressions revealed 4 distinct affective configurations: Social Engagement, Object Engagement, Passive Withdrawal, and Active Protest. These affective configurations were differentially distributed among the different interactive contexts of the Face-to-Face Still-Face Paradigm. It is suggested that behaviors and facial expressions are fundamental expressive units flexibly organized into configurations that convey messages about the infant's internal state and intentions. Furthermore, it is hypothesized that the basic units of the infant's experience are these distinct affective configurations of emotion and behavior. PMID- 7982366 TI - In vitro and in situ survivals of bacterial populations added to fresh water environments. AB - The fate of Aeromonas hydrophila, Alcaligenes denitrificans, Vibrio cholerae non 01, Pseudomonas putida and four different isolates of Escherichia coli in fresh river water were assessed by using different microcosms (i.e., membrane diffusion chamber and Erlenmeyer flask). When water samples were incubated at 16 +/- 1 degrees C, the differences in extent of survival among test bacteria were in general not significant. If the incubation temperature was raised to 29 +/- 1 degrees C, in the in situ studies, none of the added bacterial population could be detected by Day 3. In the in vitro studies, two of the four E. coli tested remained detectable by Day 3. Similarly, populations of the introduced A. hydrophila, P. putida and A. denitrificans were still detectable by Day 5. In general, all test bacteria survived better under low incubation temperature, regardless of whether the experiments were carried out under in vitro or in situ conditions. The results clearly indicated that when studying the fate of the introduced bacteria in the aquatic environment, in situ study was definitely required, especially in the summer time. PMID- 7982367 TI - Antimicrobial activity of sulfur dioxide to certain lactic acid bacteria isolated from wines. AB - This study was conducted to investigate the relationship between pH and the toxicity of sulfur dioxide against homo- and hetero-lactic acid bacteria isolated from American acidic wines. Malolactic fermentation was found to be growth associated in homo- and hetero-lactic strains. The pH of CBB broth had an insignificant effect on the specific death rate of these strains; the concentration of molecular sulfur dioxide had a great effect on the specific death rate and malate degradation. Laboratory or freshly isolated strains were exposed to various concentrations of free sulfur dioxide at pH 3.8 and 3.4. At pH 3.4, sulfur dioxide was more effective against lactic acid bacteria than at pH 3.8 since more was present as molecular sulfur dioxide and causing an increase in the specific death rate. Pediococcus strain BB was more resistant to sulfur dioxide than those hetero-lactic fermentation strains such as Leuconostoc oenos PSU-1 and ML-34. The effect of sulfur dioxide concentration on the viability of L. oenes ML-34, PSU-1, and Pediococcus strain BB appeared to be biphasic. No or little L-malic acid was degraded when the homo- and hetero-fermentative strains were killed by sulfur dioxide. PMID- 7982368 TI - Salbutamol in treatment of bronchial asthma--comparison of controlled release tablet with standard tablet. AB - Salbutamol in controlled release tablet form was compared to salbutamol in standard tablet form for the management of patients with bronchial asthma. A total of twenty asthmatic patients enrolled in the study were classified into two groups, ten patients each, for a cross-over study. Group 1 received controlled release tablets for a 2 to 3 week period, and were then shifted to standard tablets for another similar period. Group 2 received standard tablets first and was then shifted to controlled release tablets. Patients were required to record symptom scores during therapy, including sleep disturbance, chest tightness, wheezing, cough, sputum production and inhalational bronchodilator use. Measurements of peak expiratory flow rate (PEFR) were also done, as well as record made of side effects experienced. The result showed that a lower symptom score was found in patients receiving controlled release tablets than in patients receiving standard tablets (p < 0.001 for sleep disturbance, p < 0.005 for sputum formation and p < 0.001 for total score). There was a higher PEFR in patients receiving controlled-release tablets than in patients receiving standard tablets (p < 0.001). Side effects with tremor were observed in 30% of both groups of patients with a slightly higher degree in the patients receiving standard tablets (statistically not significant). In conclusion, salbutamol of controlled release tablet form obtains a better therapeutic response than standard tablets in the management of patients with bronchial asthma. PMID- 7982369 TI - Analysis of a new subtype of HIV-1 gag sequence from a case of vertical transmission in Taiwan. AB - A Taiwanese woman who lived with a presumably bisexual man of German nationality, and her infant daughter were found to be seropositive for HIV-1. From DNA preparations of peripheral blood mononuclear cells of the mother-infant pair, we amplified a segment, about 560 base pairs (bp), of gag portion of HIV-1 provirus by using polymerase chain reaction (PCR). The high degree of homology (94.7 97.5%) among clones (TM-1 and TM-2 from the mother, and TC-1 and TC-2 from the infant) of gag sequence provided a molecular epidemiological evidence for vertical transmission. However, these sequences exhibited lower degrees of homology (85.1-87.0%) with the corresponding gag segment of a North American HIV 1 subtype (HXB2), and that of a Zairean HIV-1 subtype (Z2Z6). The disparity of sequences between these Taiwanese clones and those of HXB2 and Z2Z6 was particularly prominent in the first (5' proximal) 200 bp, as shown by the low degree of homology (74.8-79.6%) when sequences of TM and TC clones which represented the first 200 bp were compared with those of HXB2 and Z2Z6. The sequence dissimilarity of these clones as compared with HXB2 manifested as transitions more frequently than transversions. Transitions involving G/A to A/G changes were more frequent than those involving T/C to C/T. Transversions involving G/A to T/C changes were slightly more frequent than those involving T/C to G/A changes for all clones except for TM-2 which showed an equal frequency. Presence of stop codons in each of the reading frames of these clones suggests that these may represent defective viral quasispecies. The deduced amino acid sequences from available open reading frames of these clones showed also distinct dissimilarities to HXB2 or Z2Z6. These findings indicate the presence of a gag subtype of HIV-1 which, according to the phylogenetic tree analysis, would represent a new subtype distinct from other known subtypes. PMID- 7982370 TI - [Color Doppler sonography-guided percutaneous alcohol instillation in the therapy of functionally autonomous thyroid nodules]. AB - In a prospective study, 26 patients (18 women, 8 men; mean age 74 [51-92] years) with clinically and biochemically confirmed hyperthyroidism and autonomous thyroid nodules, as proven by scintigraphy and colour Doppler ultrasound (CDUS), the nodular tissue was destroyed by alcohol injection. All patients had multinodular goitre, eleven with solitary adenoma and 15 with two or more adenomas. Under continuous CDUS monitoring 2-4 ml of 96% ethanol per injection were instilled in a total of 87 sessions (mean of 3.3 injections per patient). Minor side effects (pressure sensation, pain, reddening) occurred with five injections. The effect of the treatment was a reduction in size and cystic degeneration of the nodule, as well as decreased vascularization as demonstrated by CDUS. A euthyroid state was achieved, without any additional thyrostatic drugs, within 5 weeks in 18 of the 26 patients, while in eight the initial carbimazole dosage could be reduced to a quarter. After 6 weeks 11 nodules had become scintigraphically inactive. In 12 patients the technetium uptake had been reduced and initially suppressed paranodular tissue again showed functional activity. These observations indicate that the described method is an efficacious and cost-effective out-patient procedure with few side effects for the treatment of hyperthyroidism associated with single or several autonomous thyroid nodules. The localization of the hyperactive adenomas should be done together with scintigraphy and CDUS. PMID- 7982371 TI - [Esophagomediastinal fistulae as a rare complication of tuberculosis in an HIV infected patient]. AB - A 57-year-old man with an HIV infection, diagnosed a year ago, complained of fever and cough. The haemoglobin level was 7.5 g/dl, white cell count 3800/microliters, T-helper cell count 60/microliters and the CD4-CD8 ratio 0.1. Erythrocyte sedimentation rate was raised to 21/39 mm. Bacteriological tests were at first negative. The chest radiograph showed slight widening of the upper mediastinum which further increased over the next 10 days, at which time it also revealed a shadow in the right upper lobe. Computed tomography suggested necrotizing mediastinal lymph-nodes. Treatment was begun with rifampicin (600 mg daily) ethambutol (1.2 g daily), pyrazinamide (1.5 g daily) and ciprofloxacin (500 mg twice daily). Oesophagoduodenoscopy, performed after 3 weeks, revealed several fistulae which, after ingestion of contrast medium, were demonstrated to communicate with the mediastinum, presumably as a result of lymph-node liquefaction. Mycobacterium tuberculosis was demonstrated in gastric juice, sputum and stool only after tuberculostatic drugs had been started. PMID- 7982372 TI - [Gnathostomiasis after a stay in Thailand]. AB - During a 4-week holiday in Thailand a 13-year-old boy from Germany briefly fell ill with diarrhoea without blood-tinged stools and fever. 5 months later oedematous, reddish swellings occurred, at first on the right upper arm, later over the right side of the chest. Especially at night these swellings were associated with severe local and generalized itching. Bilaterally the axillary lymph-nodes were hard and slightly enlarged. There was a marked eosinophilia of 56%, the white count was 22,700/microliters and the serum level of IgE was raised to 1777 IU/ml. No worm eggs or larvae were found in the stool. Enzyme-linked immunosorbent assay, using larvae of Gnathostoma spinigerum as antigen, demonstrated antibodies against this nematode. Gnathostomiasis having been diagnosed treatment was started with albendazole (200 mg twice daily for 21 days), after which the boy was symptom free. After 2 months the eosinophilia had regressed to 10%, the white cell count was normal and the antibody titre had fallen. PMID- 7982373 TI - [The clinical importance of the polymerase chain reaction in infectious disease diagnosis]. PMID- 7982374 TI - [The indications for surgery in asymptomatic high-grade aortic valve stenosis]. PMID- 7982375 TI - [Leukoencephalopathy after the intrathecal administration of cytostatics in acute lymphatic leukemia]. PMID- 7982376 TI - [The enteropathogenicity of chlamydiae]. PMID- 7982377 TI - [The fibromyalgia syndrome]. PMID- 7982378 TI - [The fibromyalgia syndrome]. PMID- 7982379 TI - [The fibromyalgia syndrome]. PMID- 7982380 TI - [The fibromyalgia syndrome]. PMID- 7982381 TI - [The fibromyalgia syndrome]. PMID- 7982382 TI - [A "look-back" study of the German Red Cross Blood Donor Service]. PMID- 7982383 TI - Spectral analysis of heart rate variability during quiet sleep in normal human fetuses between 36 and 40 weeks of gestation. AB - Respiratory sinus arrhythmia (RSA) is a clinical manifestation of the parasympathetic nervous system which can be identified in the high-frequency region of the heart rate variability (HRV) power spectrum. The purpose of this study was to determine the relative contribution of RSA to overall HRV for human fetuses in quiet sleep. The study population consisted of 13 normal human fetuses between 36 and 40 weeks of gestation for whom data were collected during spontaneous breathing and normally occurring apneic periods. Fetal breathing was monitored continuously using real-time sonography. The fetal electrocardiogram was captured transabdominally in 3-min blocks at a rate of 833 Hz and fetal R waves were extracted from the raw signal using adaptive signal processing techniques. Fetal behavioral state was determined at the beginning and end of each 3-min data collection period. The fetal R-wave interbeat intervals (IBIs) were converted to equally-spaced, time-based data, and linear detrending of the time series was accomplished by subtracting the mean heart period from each weighted IBI. Total power (TP, 0.0-2.5 Hz) was divided into RSA (0.4-1.0 Hz), high-frequency (HF, 0.2-2.5 Hz), low-frequency (LF, 0.04-0.2 Hz), and very-low frequency (VLF, 0.0-0.04 Hz) regions, and the power densities were summed to determine the absolute power for each frequency component. A total of 81 3-min blocks (mean per subject 6.3, range 2-14) were available for analysis. Eleven (85%) of 13 fetuses demonstrated a HF peak during fetal breathing, and RSA accounted for approximately 20% of the TP.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7982384 TI - Patterns of fetal breathing in the baboon vary with EEG sleep state. AB - This report examines the hypothesis that the characteristics of breathing activity of the fetal baboon are modulated with respect to sleep state in a fashion similar to that observed in the human fetus. The pattern of fetal breathing activity was examined in relationship to electroencephalographic (EEG) sleep state in studies of six fetuses of chronically monitored pregnant baboons at 143-148 days of gestation (term, 175-180 days). Fetal breaths were defined by fluctuations of tracheal fluid pressure. EEG sleep states were defined with an automated method for discrimination of EEG patterns that are standard indices of quiet and active sleep in immature primates. During more than 250 h of recorded data, the fetuses spent on average 33.3 +/- 3.9% of time in EEG quiet sleep. In comparisons across state the fetuses spent significantly (P = 0.001) less time breathing during quiet than active sleep (49.5 +/- 6.8 vs. 69.0 +/- 3.8%). The inspiratory and expiratory time intervals of fetal breaths were not differentiated by EEG state but, the mean breath to breath interval was significantly (P < 0.001) longer in EEG quiet sleep. In addition to these differences in incidence and time interval of breaths, during epochs of breathing, there was a significantly slower rate, lower amplitude, and lower variability of rate of breathing in quiet sleep (all P-values < 0.02). Thus, periodic breathing activity in the fetal baboon is present in both quiet and active EEG sleep states. Sleep states have a powerful influence on patterns of fetal breathing in the non-human primate, directly comparable to the human fetus. PMID- 7982385 TI - Hourly fetal urinary production rate and blood velocity waveforms in the fetal renal artery relative to fetal heart rate pattern and fetal eye movements in normal pregnancies at 30-32 weeks of gestation. AB - In 14 normal pregnancies at 30-32 weeks of gestation, bloodflow velocity waveforms in the fetal renal artery and fetal micturition were studied in relation to fetal heart rate pattern (FHRP) and fetal eye movements. PI in the fetal renal artery was significantly lower in the presence of FHRP-B and eye movements separately and in combination compared with FHRP-A and absent eye movements separately and in combination. Fetal urinary output was higher in the absence of fetal eye movements. There was an inverse relationship between renal artery PI and fetal heart rate. However, since mean fetal heart rate in the various state variables was not essentially different, no standardization for heart rate was necessary. No correlation existed between renal artery PI and fetal urinary production rate. It can be concluded that in the normal fetus at 30 32 weeks of gestation, renal artery PI demonstrates a significant reduction in the presence of FHRP-B and fetal eye movements separately and in combination, suggesting reduced downstream impedance at renal level. However, the decrease in fetal micturition in the presence of fetal eye movements, suggests that reduced urinary output is determined by changes in fetal central nervous system activity rather than by changes in fetal renal perfusion. PMID- 7982386 TI - Maternal high-risk factors and severity of growth deficit in small for gestational age infants. AB - The relationship between maternal risk factors and severity of fetal growth deficit was evaluated in a population of 613 small for gestational age (SGA) infants and 784 appropriately grown controls. The severity of growth deficit among SGA infants was expressed as 'fetal growth ratio' (observed/expected birthweight, where expected birthweight is the mean birthweight of the Italian population for a given gestational age). In multivariate models, preeclampsia was the only maternal high-risk factor positively correlated with a more severe growth deficit among SGA infants. Chronic cardiac or renal maternal diseases and female fetal sex were associated with mild forms of SGA, thus showing an inverse relationship with severity of growth deficit. Finally, the association between maternal smoking in pregnancy, low (< 0.2 kg/week) maternal weight gain, low (< 50 kg) pre-pregnancy weight, severe (Hb, < 8 g/dl) maternal anaemia, low education (< 6th grade), history of a previous low birthweight infant or recurrent spontaneous abortion, nulliparity and SGA was homogeneous across the severity strata of fetal growth deficit. PMID- 7982387 TI - Postnatal changes in serum retinol status in very low birth weight infants. AB - BACKGROUND: Retinol deficiency may contribute toward the development of chronic lung disease in very low birth weight (VLBW) infants. We examined the retinol status during early infancy in VLBW infants from birth to 6 weeks 'post-term'. METHODS: Concentrations of serum retinol (SR) and its carrier proteins, retinol binding protein (RBP), and transthyretin (TTR), were determined at birth, then weekly for 8 weeks, and at 4-6 weeks 'post-term' in preterm infants of less than 34 weeks gestation. The SR values of umbilical cord blood at birth from the preterm infants were compared to the maternal SR levels as well as to cord SR levels of term infants. RESULTS: From 24 through 33 weeks gestation, umbilical cord SR at birth was significantly lower than, but did not correlate with, maternal SR (P < 0.01). The cord SR in term infants was also higher than that in preterm infants (262 +/- 68 vs. 183 +/- 67 micrograms/l, P < 0.01). Longitudinal profiles of SR in 18 VLBW infants showed that, despite regular retinol supplementation, there was a decline in SR after birth, reaching a nadir of 128 +/- 40 microgram/l at 5-7 weeks (P < 0.001), followed by an increase toward levels comparable to those seen in full term infants. At follow-up at the corrected age of 4-6 weeks 'post-term', SR levels in VLBW infant (222 +/- 74 micrograms/l) had returned to within the normal range for term cord SR values. The concentrations of RBP also showed a similar biphasic pattern. Transthyretin levels did not change for 8 weeks but increased significantly at 4-6 weeks 'post term'. CONCLUSIONS: Current practices of retinol supplementation in VLBW infants fail to maintain adequate retinol status in those infants during the neonatal period. Further efforts to improve the retinol status in these infants should be explored. PMID- 7982388 TI - Effect of moderate NO2 air pollution on the lung function of children with asthmatic symptoms. AB - In the course of a 2 1/2-year longitudinal study, the influence of outdoor NO2 and of the heating device at home on lung function was investigated in 467 children of school age in the urban area of Freiburg. Data were gathered in three surveys using standardized interviews, lung function measurements, skin prick tests with inhalant allergens, and NO2 measurements from October to April near the child's home. Regarding the lung function of a subpopulation with asthmatic symptoms (n = 106) in the three consecutive surveys, multivariate regression analyses adjusted for confounders indicate negative associations between five dependent variables, FEV1%FVC (P = 0.004), FEV1% (P = 0.02), MEF75% (P = 0.038), MEF50% (P = 0.052), and MEF25% (P = 0.002), on the one hand, and outdoor NO2 for average NO2 concentrations exceeding 40 micrograms/m3 on the other. The use of individual room heaters is associated with decreased lung function and is significant only for FEV1%FVC (P = 0.033). Neither NO2 nor individual room heating is significantly associated with one of the lung function parameters in the subpopulation without asthmatic symptoms (n = 361). In conclusion, children with asthmatic symptoms are identified as being susceptible to having reduced lung function under outdoor air pollution where average NO2 concentrations exceed 40 micrograms/m3. PMID- 7982389 TI - The impact of soil lead abatement on urban children's blood lead levels: phase II results from the Boston Lead-In-Soil Demonstration Project. AB - The Boston Lead-In-Soil Demonstration Project was a randomized environmental intervention study of the impact of urban soil lead abatement on children's blood lead levels. Lead-contaminated soil abatement was associated with a modest reduction in children's blood lead levels in both phases of the project; however, the reduction in Phase II was somewhat greater than that in Phase I. The combined results from both phases suggest that a soil lead reduction of 2060 ppm is associated with a 2.25 to 2.70 micrograms/dl decline in blood lead levels. Low levels of soil recontamination 1 to 2 years following abatement indicate that the intervention is persistent, at least over the short-term. Furthermore, the intervention appears to benefit most children since no measurable differences in efficacy were observed for starting blood and soil lead level, race, neighborhood, gender, and many other characteristics. However, soil abatement did appear to be more beneficial to children in the higher socioeconomic classes, with low baseline ferritin levels, and who spent time away from home on a regular basis and lived in nonowner occupied housing, and with adults who had lead related hobbies and almost always washed their hands before meals. Children who lived in apartments with consistently elevated floor dust lead loading levels derived almost no benefit from the soil abatement. It was not possible to separate the effects of the variables that had a beneficial impact on efficacy because they were closely correlated and the number of subjects was small. We recommend that further research be conducted to identify subgroups of children to whom soil lead abatement might be targeted. PMID- 7982390 TI - Pregnancy outcome in Sweden after the Chernobyl accident. AB - OBJECTIVE: To study pregnancy outcome including development of childhood cancer in areas within Sweden with the highest radioactive fallout after the Chernobyl accident in 1986. METHODS: Various Swedish health registries were used in order to identify all pregnancies and their outcome in Sweden according to the measured radioactive fallout. RESULTS: A reduction in conception rate occurred after the accident, as well as possible increase in induced abortion rate during the fall after the accident. No changes in the rate of spontaneous abortions or congenital malformations occurred in pregnancies exposed at the time of the accident. There was a temporary increase in low birth weight which could well be random. Among infants conceived after the accident, a slight excess of Down syndrome infants was found in the most exposed areas but this observation is based on small numbers. No certain excess of childhood cancer was seen in the most exposed areas, but three infants, in utero at the time of the accident, developed leukemia. CONCLUSIONS: No major effects on pregnancy outcome were seen but the indicated increase in Down syndrome and childhood leukemia--if not random--could be a result of radioactive exposure. PMID- 7982391 TI - No indication of in vivo methylation of inorganic mercury in chloralkali workers. AB - It has been shown in vitro that human oral and intestinal bacteria are able to methylate inorganic mercury (Hg) to methylmercury (MeHg). In vivo methylation has been reported for guinea pigs, and several studies have found higher levels of organic Hg in blood of workers exposed to inorganic Hg. In search for indications of in vivo methylation of Hg, we determined total Hg in urine (U), plasma (P), and erythrocytes (Ery), and MeHg in erythrocytes, in 22 chloralkali workers exposed to inorganic Hg, and in 22 age-matched referents. The subjects in both groups ate fish not more than once a week. MeHg was determined using ion exchange separation and cold vapor atomic absorption spectrometry. The mean concentrations of total mercury in chloralkali workers and referents were 26 vs 2.3 micrograms/g creatinine (U-Hg), 9.7 vs 1.8 ng/g (P-Hg), and 11.4 vs 5.6 ng/g (Ery-Hg). The mean Ery-MeHg concentrations were 3.0 vs 3.7 ng/g, and there were no correlations between Ery-MeHg on the one hand and U-Hg or P-Hg on the other. Our results indicate no significant in vivo methylation of inorganic Hg in man. Contradictory results from previous studies may be due either to bias owing to fish consumption or to analytical shortcomings. PMID- 7982392 TI - A multidisciplinary study of lead-exposed subjects. I. Delayed target detection P 300 latency, an electrophysiological parameter, correlates with urinary delta ALA. AB - Visual event-related potentials, generated while performing a target detection (oddball) task, were successfully evaluated in 21 out of 34 individuals occupationally exposed to lead and 40 out of 56 nonexposed controls who were examined. The blood lead level of the lead-exposed subjects ranged from a mean of 29 to 53 micrograms Pb/dl blood in three exposed subgroups, while that of the control group was 7.7 micrograms Pb/dl blood. The latencies of the N2 and P300 components of the visual event-related potential were significantly longer in the lead-exposed subjects. Both the N2 and P300 latencies significantly correlated with the blood lead levels of the subjects. In addition, the P300 latency correlated with the concentration of delta-aminolevulinic acid (delta-ALA) in urine. This in part could be due to elevated delta-ALA levels interacting with gamma-aminobutyric acid (GABA) receptor neurons. The results indicate that lead affects mental function even at permitted levels of exposure. They strengthen the conclusion, based on biochemical and hematological assays, that the maximum permitted blood lead level of 50 micrograms Pb/dl blood is not safe and should be reduced. PMID- 7982393 TI - Effect of arsenic exposure on alveolar macrophage function. I. Effect of soluble as(III) and as(V). AB - Despite potential differences in the mechanism and potency of toxicity between the two common oxidation states of arsenic (As(III) and As(V)), assessments of the risk from inhaled arsenic generally ignore the oxidation state of inorganic arsenicals. Differences between potency and toxicity of As(III) and As(V) were evaluated by determining alteration in function of pulmonary alveolar macrophages (PAM) following in vivo and in vitro exposure to soluble arsenic. Male Sprague Dawley rats were used throughout. One day following intratracheal instillation of 1 mg/ml (as arsenic) of either sodium arsenite (As(III)) or sodium arsenate (As(V)), PAM were lavaged and analyzed for alterations in superoxide (O2-), prostaglandin E2 (PGE2), and tumor necrosis factor (TNF-alpha) production. There were no differences in bronchoalveolar lavage fluid PGE2 or TNF-alpha. PAM lavaged from As(V)-exposed animals showed significant increases in O2- production. In vivo exposure to either oxidative form of arsenic decreased basal and lipopolysaccharide (LPS)-induced release of TNF-alpha production by PAM, but did not suppress LPS-induced production of PGE2. To test the direct effects of arsenic on PAM function, PAM were lavaged from control animals and exposed, in vitro, to either arsenical for up to 24 hr to concentrations of 0.1 to 300 micrograms/ml arsenic. Doses used were not cytotoxic to PAM, since LDH release was not significantly increased, even at the highest dose. Significant dose dependent inhibition of O2- production was only evident after 24 hr exposure to arsenicals. As(III) was more potent than As(V), inhibiting O2- at concentrations as low as 0.1 micrograms/ml compared to 1.0 micrograms/ml of As(V). Suppression of LPS-induced release of TNF-alpha also occurred at lower concentrations of As(III), 50% inhibition at 0.15 micrograms/ml, compared to As(V), 50% inhibition at 1.8 micrograms/ml. While As(III) exposure had no affect on PGE2 production, As(V) caused inhibition of LPS-induced PGE2 production at concentrations above 1.0 micrograms/ml. Differences between As(III) and As(V) indicate that different mechanisms and/or potencies exist between the two arsenic species. Arsenic induced alteration in PAM function may compromise host defense against infections and alter immune surveillance. PMID- 7982394 TI - Mercury distribution in cortical areas and fiber systems of the neonatal and maternal adult cerebrum after exposure of pregnant squirrel monkeys to mercury vapor. AB - Pregnant squirrel monkeys were exposed 5 days/week to mercury vapor at a concentration of 0.5 mg Hg/m3 air for 7 hr/day, or at 1 mg Hg/m3 air for 4 or 7 hr/day. The calculated total mercury absorption ranged between 0.8 and 5.4 mg (range of daily absorption 0.04-0.07 mg). The mercury concentration in the cerebral occipital lobe of the offspring ranged between 0.20 and 0.70 microgram/g tissue, and in the mothers between 0.8 and 2.58 micrograms/g tissue. Mapping of the distribution of mercury in the neocortical layers of the maternal brains revealed that the pyramidal cells contained more visualized mercury than the other neurons. In addition, the mapping disclosed that the deeper the pyramidal cells were situated the more mercury they contained. In the offspring brains, no laminar distribution pattern was found. In the hippocampal formation, the pyramidal cells again contained more mercury than the other neurons. By contrast, the stratum granulosa of the dentate gyrus was always devoid of visualized mercury. The claustrum and the amygdaloid complex always contained mercury. In the fiber systems, the offspring brains contained more mercury than the adult brains. Mercury was found in both glial cells and neurons both in the cortical areas and in the fiber systems. PMID- 7982395 TI - Lead toxicity via arachidonate signal transduction to growth responses in the splenic macrophage. AB - Lead chloride modulated the macrophage cell surface growth signal-transduced, lipid second messenger prostaglandin E2 (PGE2), concomitant with cell differentiation. In virgin macrophage, PGE2 was increased by lead in a dose dependent manner, suggesting suppression of the immune function (inversely regulated by PGE2). Upon stimulation by bacterial endotoxin, lead-treated cells displayed decreased PGE2 with immune augmentation as tested by zymosan particle ingestion. These effects were simulated by a glutathione synthesis inhibitor around 10 microM lead, and by cycloheximide around 50 microM lead, suggesting a mechanism similar to viral infection. PMID- 7982396 TI - Chiral separations by capillary electrophoresis: present state of the art. AB - Capillary electrophoresis is a powerful tool for chiral separation of ionogenic enantiomers in solutions. This article brings an overview of the theory of electrophoretic separations with special emphasis on enantiomer-chiral selector equilibria, followed by a survey of indirect separations, based on formation of diastereomers with different electrophoretic mobilities, and a comprehensive appraisal of direct separations when the chiral recognition stems from (i) host guest interactions using cyclodextrins and crown ethers as hosting agents, (ii) ligand exchange mechanism, (iii) affinity interactions or (iv) a combination of solute-chiral selector interactions with micellar electrophoretic transport. Finally, some trends in chiral separations by capillary electrophoresis are discussed. PMID- 7982397 TI - Separation of enantiomers of N-acetylcysteine by capillary electrophoresis after derivatization by o-phthaldialdehyde. AB - The optical purity of N-acetyl-L-cysteine was tested by capillary electrophoresis. The D-enantiomer can be found down to a ratio of 0.4:99.6 within 4 min without the use of the D-form or the racemate as a standard. The efficiency was optimized during method development up to a theoretical plate number, N, of several hundred thousand. The migration order and the separation mechanism was explained. The assumed structure of the formed isoindole S-[2-(1-carboxy-2 methylpropyl)isoindole-1-yl]-N-acetylcysteine diastereomers was confirmed and its stability was examined. PMID- 7982398 TI - Improved separation of diastereomeric derivatives of enantiomers by a physical network of linear polyvinylpyrrolidone applied as pseudophase in capillary zone electrophoresis. AB - Diastereomeric analytes were separated using capillary zone electrophoresis with polyvinylpyrrolidone as polymeric additive to the buffer solution. As test substances derivatives of D- and L- alpha-amino and alpha-hydroxy acids formed by reaction with (+)-O,O'-diacetyl- and (+)-O,O'-dibenzoyl-L-tartaric anhydride, respectively, were used. The physical network formed by the linear polymer is supposed to act as a kind of pseudophase. It was found that the network affects the mobility of diastereomeric compounds to a different extent, enhancing the selectivity of the system. In nearly all cases of aromatic acids the diastereomer carrying the D-amino acid was more strongly retained than the L-isomer, as opposed to the situation with aliphatic acids. PMID- 7982399 TI - A theoretical approach to chiral capillary electrophoresis with some practical implications. AB - A simple model has been proposed which explains enantiomeric resolution in capillary electrophoresis in terms of differential interactions with a chiral selector and differential migration of the two enantiomer-chiral selector complexes. The equations derived allow predictions to be made and there is good support for the model in literature data. PMID- 7982400 TI - Introduction of migration indices for identification: chiral separation of some beta-blockers by using cyclodextrins in micellar electrokinetic capillary chromatography. AB - Because of the different physiological impact that stereoisomers may have, it is often vital to separate these forms from one another. Because of their structural similarity, the separation is usually difficult to achieve and zones may elute very close to each other. This is a particular problem in capillary electrophoresis, where the repeatability of absolute migration times is fairly poor, mainly due to the irreproducibility of the electroosmotic flow. The separation is usually repeatable, however, and when the disturbing effects are eliminated by using a migration index system incorporating two marker compounds the identification of the enantiomers becomes extremely good. Relative standard deviation (RSD) values less than 0.1% for the migration index of each enantiomer were obtained in both intra-day and day-to-day (6 days) studies. The best separation was achieved with the electrolyte solution made of 40 mM borate, 32 mM sodium dodecyl sulfate (SDS), 12 mM beta-cyclodextrin (beta-CD), and 6 mM alpha cyclodextrin (alpha-CD) at pH 9.3. PMID- 7982401 TI - Separations of derivatized amino acid enantiomers by cyclodextrin-modified capillary electrophoresis: mechanistic and molecular modeling studies. AB - The enantiomers of 5-dimethylamino-1-naphthalene sulfonyl (DNS)-derivatives of selected amino acids were successfully separated using capillary electrophoresis (CE) employing cyclodextrins (CD) as enantio-selective running buffer additives. A previously described model for retention and chiral recognition in CD-modified CE is shown to adapt well in this application. Resolution of the isomers is strongly influenced by the type and concentration of cyclodextrin employed, as predicted by the model. Although data indicates differences in the electrophoretic mobilities for some of the completely complexed enantiomer pairs, selectivity generally requires exploiting differences in the amino acid-CD complexation constants for enantiomer pairs. In this work, the D-enantiomers exhibit larger formation constants and are complexed to a greater degree (elute first) at moderate CD concentration. When mixtures of amino acids are analyzed, the effects of separation conditions on general elution behavior must be considered or separated enantiomer pairs will co-elute with other enantiomers. Preliminary results aimed at predicting the strength of DNS-amino acid enantiomer CD interactions based on molecular modeling studies are presented. A statistical mechanical approach to treating computationally derived enantiomer-CD interaction energies is shown to provide reasonable correlation with separation performance. PMID- 7982402 TI - Neutral and anionic cyclodextrins in capillary zone electrophoresis: enantiomeric separation of ephedrine and related compounds. AB - Two methods for the enantiomeric separation of chiral ephedrine alkaloids (ephedrine, methylephedrine, methylpseudoephedrine and norephedrine) by capillary zone electrophoresis in uncoated capillaries were developed. Both methods were optimized to more than 100,000 theoretical plate numbers. The first method used a neutral cyclodextrin (CD) derivative: heptakis (2,6-di-O-methyl)-beta cyclodextrin at an acidic pH of 2.5 (20 mM phosphate buffer) at an 18 mM concentration. The second used a newly developed acidic CD derivative, the tetrakis[6-O-(4-sulfobutyl)]-beta-cyclodextrin sodium salt. The benefits of this new reagent for the chiral separation are a wide range of basic pH available for the enantiomeric resolution. It is also useful for other cases, e.g. preventing adsorption without additives. PMID- 7982403 TI - About some aspects of the use of charged cyclodextrins for capillary electrophoresis enantioseparation. AB - Free capillary zone electrophoresis with the negatively charged polyanion of the beta-cyclodextrin sulfobutyl ether (SBE-beta-CD) as a chiral additive was used for the resolution of basic racemic drugs. High enantioselectivity was established for some racemic compounds using extremely low (micromolar) concentrations of the chiral additive. The dependencies of the migration times and the selectivity of the enantioseparation on the concentration of the chiral additive and the pH of the run buffer were studied. Examples of the chiral separation in counter-current flows of discrete zones of the chiral selector and the racemic compound as well as separation of the neutral racemic compound thalidomide in a micellar electrokinetic chromatography-like modus were demonstrated using SBE-beta-CD. PMID- 7982404 TI - Enantiomeric separation of salbutamol and related impurities using capillary electrophoresis. AB - The enantiomeric resolution of salbutamol and its chiral and achiral related impurities is investigated using capillary electrophoresis. The effects of nine varieties of cyclodextrin, cyclodextrin concentration and organic modifier concentration were studied in an attempt to resolve all possible analytes in a complex mixture of salbutamol-related solutes. Eleven components including three enantiomeric pairs were baseline resolved using 112 mM dimethyl-beta-cyclodextrin at pH 2.5 in a citric acid/phosphate buffer. Both methanol and iso-propyl alcohol at up to 20% were found to have a deleterious effect on the separation. Binding constants and mobility values for the free and complexed forms for each solute were determined. The results are interpreted by considering the physical properties of the molecules under the conditions employed and a rationale proposed for the underlying basis for chiral and achiral selectivity. PMID- 7982405 TI - Chiral separation of basic drugs by capillary zone electrophoresis with cyclodextrin additives. AB - The enantiomers of a series of basic drugs were separated in capillary zone electrophoresis (CZE) in phosphate buffers, pH 3, containing beta-cyclodextrin or one of its derivatives as chiral selectors and uncoated fused silica capillaries thermostated at 15 degrees C. The nature of the cationic component of the background electrolyte was found to have a significant influence on achiral resolution and peak symmetry. The best results were obtained with triethanolamine, which was then used to adjust the buffer pH in all further experiments. The effects on chiral resolution of the nature and concentration of cyclodextrin, of the addition of methanol, and of capillary temperature were studied. Maximum resolution was obtained at a particular cyclodextrin concentration for each analyte, depending on the affinity of the analyte for this cyclodextrin. On the basis of the results, the effects of methanol addition and temperature on enantiomeric resolution could be explained and predicted. Numerous chiral separations are presented and suggestions for the rapid optimization of CZE enantioseparations with cyclodextrin additives are given. PMID- 7982406 TI - Quantitative applications and validation of the resolution of enantiomers by capillary electrophoresis. AB - The separation and quantitation of enantiomers is an important application of capillary electrophoresis. This paper reviews the performance and validation of capillary electrophoretic methods for this application. Limits of detection of < 0.1% are shown for determinations of minor enantiomer levels. Application areas include enantiomeric purity testing of pharmaceuticals and herbicides, reaction rate monitoring, stability testing, and clinical analysis. It is concluded that the number of quantitative application areas will undoubtedly expand as capillary electrophoresis becomes more widely established as an alternative and complement to high-performance liquid chromatography. PMID- 7982407 TI - Potential and limitations of an optically active crown ether for chiral separation in capillary zone electrophoresis. AB - Capillary zone electrophoresis using optically active 18-crown-6 tetracarboxylic acid (18C6H4) as chiral selector was studied for the enantiomeric separation of primary amines. From the separation of a variety of pharmaceutical drug substances, amino alcohols and amino acids, conclusions could be made concerning the influence of the chemical structure of the analytes on the separation. In addition, the effects of experimental parameters such as pH, proportion of organic modifier and buffer composition on the separation are discussed. A synergistic effect obtained by the joint application of 18C6H4 and a cyclodextrin was exploited to resolve analytes which were separated neither by the crown ether nor by the cyclodextrin. PMID- 7982408 TI - Enantiomer separation using mobile and immobile cyclodextrin derivatives with electromigration. AB - The principle of electrochromatography is applied to enantiomer separation with wall-coated capillaries of 50 microns (ID). As chiral stationary phase an immobilized polysiloxane containing chemically bonded monokis-6-O-octamethylene permethyl-cyclodextrin (beta- or gamma-Chirasil-Dex) was used. The results are compared with the conventional method of adding cyclodextrin derivatives as chiral pseudostationary phase to the running buffer. PMID- 7982409 TI - On the possibility of performing chiral wall-coated open-tubular electrochromatography in 50 micron internal diameter capillaries. AB - Recent results have demonstrated acceptable enantiomer separations in open, 50 microns internal diameter capillaries, coated with a chiral stationary phase, a technique known as electrochromatography. According to existing literature, smaller column diameters, 10 microns or less, are generally preferred for this mode of operation. The conditions under which the wider columns can be used are discussed. PMID- 7982410 TI - Separation of enantiomers by affinity electrokinetic chromatography using avidin. AB - Avidin, a basic protein isolated from egg white, was employed as a chiral selector in affinity electrokinetic chromatography (EKC) for the separation of acidic enantiomers. Optical isomers of vanilmandelic acid, warfarin, ibuprofen, ketoprofen, flurbiprofen, and folinic acid were successfully resolved within 20 min with 25 microM avidin in a linear polyacrylamide-coated capillary under weakly acidic conditions. The effects of pH, the concentration of avidin, addition of an organic solvent such as ethanol and 2-propanol, and temperature on enantioselectivity were investigated. The choice of pH and the organic solvent additive was critical to improve the separation. Some general considerations about affinity EKC are also described, based on a simple one-site interaction model. PMID- 7982411 TI - Quantitation in chiral capillary electrophoresis: theoretical and practical considerations. AB - Capillary electrophoresis (CE) represents a decisive step forward in stereoselective analysis. The present paper deals with the theoretical aspects of the quantitation of peak separation in chiral CE. Because peak shape is very different in CE with respect to high performance liquid chromatography (HPLC), the resolution factor Rs, commonly used to describe the extent of separation between enantiomers as well as unrelated compounds, is demonstrated to be of limited value for the assessment of chiral separations in CE. Instead, the conjunct use of a relative chiral separation factor (RCS) and the percent chiral separation (% CS) is advocated. An array of examples is given to illustrate this. The practical aspects of method development using maltodextrins--which have been proposed previously as a major innovation in chiral selectors applicable in CE- are documented with the stereoselective analysis of coumarinic anticoagulant drugs. The possibilities of quantitation using CE were explored under two extreme conditions. Using ibuprofen, it has been demonstrated that enantiomeric excess determinations are possible down to a 1% level of optical contamination and stereoselective determinations are still possible with a good precision near the detection limit, increasing sample load by very long injection times. The theoretical aspects of this possibility are addressed in the discussion. PMID- 7982412 TI - Separation of alpha-hydroxy acid enantiomers by high performance capillary electrophoresis using copper(II)-L-amino acid and copper(II)-aspartame complexes as chiral selectors in the background electrolyte. AB - Optical isomers of some alpha-hydroxy acids, namely 2-, 3-phenyllactic acid, mandelic, p-hydroxy-, m-hydroxy and 3,4-di-hydroxymandelic acid, were separated by means of capillary zone electrophoresis in free solution, using copper (II) complexes with L-amino acid or aspartame ligands in the background electrolyte. The concentration and the pH dependence of the enantiomer separations have been studied in the cases of different chiral ligands and/or analytes. With the use of L-proline as ligand only the optical isomers of 3-phenyllactic acid were resolvable, whereas using L-hydroxyproline the D and L forms of all compounds, except for 2-phenyllactic acid, were separated. Better results were obtained with aspartame as chiral ligand. PMID- 7982413 TI - From GISSI-1 to GUSTO: ten years of clinical trials on thrombolysis. GISSI-3 Steering Committee. PMID- 7982414 TI - Calcium infusion induces myocardial ischaemia in patients with coronary artery disease by a mechanism possibly adenosine mediated. AB - In the first part of the study five healthy volunteers were submitted to i.v. infusion of 0.2 mM.kg-1 b.w. of calcium gluconate over 20 min. Total calcium (atomic absorption method), ionized calcium (ion-selective electrode method) and adenosine (HPLC technique) were measured at the following times: 0 (basal), 5, 10, 15, 20 (end of infusion), 25, 30, 35, and 50 min. The increase in total and ionized calcium serum levels was associated with a significant increase in adenosine plasma levels (from 207 +/- 41 to 362 +/- 63 nM.l-1, P < 0.001). Since the increase in adenosine plasma levels, obtained either with adenosine or dipyridamole (an adenosine reuptake inhibitor), has been used to test the coronary reserve in coronary artery disease (CAD) patients, in the second part of the study we compared the effects of calcium infusion with dipyridamole in 15 subjects. Pharmacological stress tests were evaluated by monitoring two dimensional echocardiography and ECG. Ten patients had positive results with both the dipyridamole stress test and the calcium infusion. Our results show that calcium infusion induces an increase in adenosine plasma levels that can elicit a dipyridamole-like coronary steal, thus suggesting the central role of extracellular adenosine in myocardial ischaemia. PMID- 7982415 TI - Effect of magnesium on restenosis after percutaneous transluminal coronary angioplasty: a clinical and angiographic evaluation in a randomized patient population. A pilot study. The Ichilov Magnesium Study Group. AB - Restenosis is a major clinical problem following successful percutaneous transluminal coronary angioplasty. Since magnesium has vasodilator and antithrombotic effects, this study was designed to evaluate its potential to decrease the rate of restenosis. In an open-labelled, randomized controlled study, 148 patients underwent successful coronary angioplasty. Ninety-eight patients were treated with 46-52 mmol/18-20 h intravenous magnesium sulphate (groups M1 and M2), and 49 of them continued with oral supplements of magnesium hydroxide 600 mg.day-1 (group M2). The other 50 patients served as controls (group C). Coronary angiography was performed before, immediately after and at 6 months follow-up or earlier if clinically indicated. Clinical, laboratory, ergometric and radionuclide evaluations were also carried out. One hundred and thirty-nine patients (94%) with 163 dilated segments completed the study. Intravenous magnesium was well tolerated. The cross-sectional area at the site of angioplasty increased by 3.55 +/- 2.01 mm2 in groups M1 and M2 compared with an increase of 2.90 +/- 1.63 mm2 in the control group, (P = 0.03). A trend towards a lower rate of restenosis (> 50% reduction in luminal diameter) was noticed in the magnesium groups (28/110, 25%) compared with the control group (20/53, 38%) P = 0.10. Oral administration of magnesium was well tolerated, did not have an additive effect on restenosis, but an improved clinical course was noted. It is concluded that intravenous administration of magnesium in patients undergoing coronary angioplasty is feasible and safe and that the beneficial trend of magnesium to prevent acute recoil and late (within 6 months) restenosis is encouraging and should promote further investigation in a larger patient population. PMID- 7982416 TI - Spectral components of short-term RR interval variability in healthy subjects and effects of risk factors. AB - Cardiac neural control can be estimated by frequency domain characterization of RR interval variations. This technique may become a clinical tool, as autonomic dysfunction is involved in the pathophysiology of sudden cardiac death. The study was designed to investigate 24-h cardiac autonomic control in 104 healthy subjects aged 40-77 years and to evaluate the impact of gender, age, smoking and physical training level. The sympathovagal balance was evaluated by spectral analysis of RR interval oscillations. The square-root of power of the high- (HF; 0.15-0.40) and low-frequency (LF; 0.04-0.15 Hz) bands were considered indexes of the vagal function and of the sympathovagal interaction, respectively. In addition, the precise centre frequency of the LF and HF oscillations was determined. The vagal mediated respiratory-dependent HF oscillation exhibited a clear circadian variation, and obtained the highest power values during sleep. The centre frequency was significantly lower during sleep (0.26 Hz vs 0.28 Hz), probably due to a slower respiratory frequency at night. Values for vagal tone were higher in physically trained subjects throughout the 24-h, and decreased by 13% for every 10-year increase in age; it was also reduced in smokers. The amplitude of the LF oscillation exhibited no clear diurnal variation. The mean LF/HF ratio was 3.1. LF power was much higher in males, was reduced by 15% per 10 year increase in age, and was lower in sedentary and smoking subjects, throughout the 24-h. The mean centre frequency of this component was reduced with advancing age (0.08 to 0.06 Hz from age 40 to 80 years). LF and HF power correlated positively, (r = 0.68), and 46% and 16% of the interindividual variation in LF and HF power, respectively, was explained by the four factors (gender, age, smoking, physical activity). Thus gender, age smoking and physical training level have a significant impact on the power and centre frequency of the HF and LF components. These effects must be addressed in investigations on autonomic balance. PMID- 7982417 TI - Na,K-pump concentration in hypertrophied human hearts. AB - Several studies have associated myocardial dysfunction with reduced myocardial Na,K-pump concentration, but whether impaired Na,K-pump capacity is a pathogenetic factor or an epiphenomenon related to accompanying cardiac hypertrophy is not established. We measured Na,K-pump concentrations in 10 hypertrophied and 11 normal weighted hearts obtained at autopsy using [3H]ouabain as ligand. Specific [3H] ouabain binding site concentration (OBC) in the left ventricle (LV) averaged 449 +/- 40 (pmol.g-1 wet weight; mean +/- SEM) in hypertrophied and 598 +/- 36 in normal weighted ventricles (P = 0.02). A trend towards lower LV OBC (-19%; P = 0.25) was found in hypertrophied hearts from patients with congestive heart failure as compared with non-failing hypertrophied hearts. In multivariate analysis with 18 variables including age and heart failure, only LV weight correlated independently with LV OBC (r = -0.61; P = 0.003). When OBC was related to either dry weight or to protein content, a 25-35% reduction was consistently found in hypertrophied LV, whereas RV OBC was similar in both groups. In conclusion, myocardial Na,K-pump concentration and thus the capacity to maintain homeostasis is reduced in LV, but not in RV, of hypertrophied hearts. Whether the moderately reduced myocardial Na,K-pump concentration is a pathogenetic factor in LV dysfunction remains to be determined. PMID- 7982418 TI - Hyperhomocysteinaemia in heart transplant recipients. AB - The aim of this study was to determine the prevalence of hyperhomocysteinaemia in cardiac transplant recipients. Three groups of subjects were studied: 27 heart transplant recipients, 14 to 63 months (mean = 36.5) after transplantation; 10 patients with moderate chronic renal insufficiency without clinical evidence of vascular disease; 17 apparently healthy individuals. Twenty-five out of 27 transplanted patients had a coronaroangiography within 6 months of homocysteine measurement. Plasma homocysteine was measured both while the subject was fasting (t0) and 6 h after administration of 0.1 g.kg-1 of methionine (t6). Hyperhomocysteinaemia was present in 14/27 fasting transplanted patients and after methionine loading. Mean plasma levels of homocysteine at t0 were higher (P = 0.03) in transplanted heart recipients (15.4 +/- 7 mumol.l-1) than in the renal patients (9.9 +/- 5 mumol.l-1) despite similar mean plasma creatinin. In eight transplanted patients with angiographic coronary abnormalities of the cardiac graft, homocysteinaemia was at t0 17.1 +/- 9 mumol.l-1 and at t6 47.8 +/- 25 mumol.l-1. In 17 transplanted patients with angiographically normal coronary arteries, plasma homocysteine levels were at t0, 13.2 +/- 4 mumol.l-1 and at t6, 46.8 +/- 25 mumol.l-1. We conclude that hyperhomocysteinaemia is common in transplanted heart recipients, and partly related to renal insufficiency. No correlation was found between hyperhomocysteinaemia and angiographic evidence of coronary atherosclerosis of the graft, but the population of the study was possibly too small to establish this correlation. PMID- 7982419 TI - Prospective evaluation of a prostacyclin-sparing aspirin formulation and heparin/warfarin in aspirin users with unstable angina or non-Q wave myocardial infarction at rest. The Antithrombotic Therapy in Acute Coronary Syndromes Research Group. AB - The aim of this trial was to compare the efficacy of combination antithrombotic therapy with a prostacyclin-sparing aspirin plus anticoagulation versus conventional aspirin plus anticoagulation, when added to antianginal therapy, in patients with unstable angina or non-Q wave myocardial infarction already being treated with aspirin. In a double-blind (for the aspirin) study, 144 prior aspirin users were randomized; 72 patients received controlled-release, prostacyclin-sparing aspirin 75 mg daily plus anticoagulation (intravenous heparin followed by warfarin to maintain the international normalized ratio at 2 3), and 72 patients received conventional aspirin 75 mg daily plus the same anticoagulation. Controlled-release aspirin was formulated to preserve endothelial cell prostacyclin synthesis. Trial therapy was begun by 13.2 +/- 12.3 h of qualifying pain, and continued for 12 weeks. The frequency of recurrent angina with electrocardiographic changes, myocardial infarction, or death, was analysed by intention to treat. At 12 weeks, events were: [table: see text] Twenty-six of the 42 (62%) recurrent ischaemic events occurred within 7 days of presentation. Four of the 144 patients (3%) experienced a major bleeding complication. It is concluded that in spite of maximal antithrombotic therapy, there is a significant failure rate of medical therapy in aspirin users presenting with unstable angina or non-Q wave myocardial infarction while at rest. Prostacyclin-sparing aspirin offers no clinical benefit over conventional aspirin. PMID- 7982420 TI - Survival after coronary artery bypass grafting. Experience from 4661 patients. AB - The duration of the reduction of mortality after coronary artery bypass grafting (CABG) is an important issue and this study was undertaken to evaluate time in relation to excess mortality among CABG patients compared with the general population. Survival was analysed in 4661 patients who had undergone their first isolated CABG. Observed survival was related to that expected among subjects from the general Swedish population stratified by age, sex and 5-year calendar period, to calculate relative survival and estimate disease-specific survival. Relative survival (including all deaths) was 94.6% at 5 years, 82.5% at 10 years, and 59.9% at 15 years. A multivariate model based on relative survival rates adjusted for age, year of surgery, severity of coronary disease, left ventricular function, and smoking habits was used. Compared with the first year of follow-up, the relative hazard (a measure of the risk of death) was at a minimum 2 years after surgery, but was dramatically increased after about 8 years. Relative survival was worsened by smoking at the time of operation and by moderate or severe left ventricular dysfunction pre-operatively. The survival rate was higher among patients operated on after 1985 than among those operated on earlier. PMID- 7982421 TI - Favourable results of treatment of narrowed saphenous vein grafts with Palmaz Schatz stent implantation. AB - Although conventional balloon angioplasty of saphenous vein grafts can be performed with an acceptable acute success and complication rate, restenosis remains a major problem. However, this may be overcome by the implantation of Palmaz-Schatz stents. Palmaz-Schatz stent deployment was performed in our institution in 43 patients who were referred for PTCA of stenosed saphenous vein grafts. Thirty-seven were located at the mid-portion of the graft, seven at the ostium and six at the distal anastomosis. Overall, we used 59 standard length (15 mm) Palmaz-Schatz stents and 22 short (7 mm) stents. In 15 lesions (30%) multiple stents were implanted in tandem to treat diffuse disease. Angiographic success was achieved in 47 of the 50 attempted lesions (94%). Major cardiac complications occurred in three patients. Two patients had procedures complicated by the development of a Q wave myocardial infarction, one of whom underwent urgent CABG. One patient died. There was no episode of subacute thrombosis. The angiographic follow-up of 37 lesions (80% of eligible lesions) at a mean time of 5 +/- 2 months (range 1-8) showed a restenosis rate of 11% and residual post-stent diameter stenosis was associated with a significantly higher restenosis rate. However, no restenosis occurred in lesions receiving multiple stents. Clinical follow-up was performed in all patients, and at a mean of 25 months after the procedure, 64% were free from clinical events, including recurrent angina. Palmaz Schatz stent implantation is an effective and safe procedure to treat narrowed vein grafts.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7982422 TI - Quantitative analysis of planar technetium-99m Sestamibi myocardial perfusion images. Clinical application of a modified method for the subtracton of tissue crosstalk. AB - Application of the Thallium-201 quantitative analysis method to Tc-99m Sestamibi planar myocardial perfusion images results in oversubtraction of tissue crosstalk, defined as 'activity within the myocardial image, which originated outside the heart'. A modified algorithm, specific for Tc-99m Sestamibi, was applied in 60 patients and the results of quantitative analysis to estimate the risk of coronary artery disease were compared with coronary angiographic findings and with visual analysis. New crosstalk planes were generated based on the results in 20 male healthy volunteers. The results in our study group indicate a higher diagnostic accuracy when circumferential profiles are generated on the basis of maximal counts compared to mean counts. Quantitative analysis was able to predict the presence or absence of CAD as accurately as visual analysis. Odds ratios were 1.07 and 1.32 respectively (P < 0.001) for both quantitative maximal uptake and visual uptake analysis. Sensitivity of visual analysis alone was 89%, increasing to 96% with combined visual/quantitative analysis. Specificity of visual analysis decreased from 79% to 64% with combined analysis. Although only minor differences are seen, the maximal count uptake profiles were found to have additional diagnostic value compared to visual analysis alone. PMID- 7982423 TI - Validity of continuous wave Doppler and colour Doppler in the assessment of aortic regurgitation. AB - Continuous wave Doppler, colour Doppler, and their combined use were compared for their validity in the semiquantitative evaluation of aortic regurgitation in 80 angiographically proven cases. The diastolic decay slope, as measured from the continuous wave Doppler signal of the aortic regurgitation, correlated well with angiographic data (r = 0.82) and, after classification in three grades, coincided in 78% of all patients. When rated on a three-grade scale the intensity of the aortic regurgitation signal measured by continuous wave Doppler corresponded with invasive data in 82% of patients, and a three-graded maximal width at the base of the colour Doppler regurgitant jet relative to the aortic outflow tract showed agreement in 71%. The best results were obtained by combining continuous wave and colour Doppler indices, which yielded agreement with angiography in 85% of patients. Subdivision of the patient group into those with pure aortic regurgitation and those with combined aortic lesions revealed less accurate gradings with both Doppler methods in the presence of aortic stenosis. PMID- 7982424 TI - Comparison of radionuclide ventriculography and 2D echocardiography for the measurement of left ventricular ejection fraction following acute myocardial infarction. AB - To compare the measurement of left ventricular ejection fraction obtained by two dimensional echocardiography and by radionuclide ventriculography in patients following acute myocardial infarction, 49 consecutive patients with acute myocardial infarction underwent echocardiography and radionuclide ventriculography on the same day, pre-discharge. Left ventricular ejection fraction was assessed by two blinded observers for each method and reproducibility was also assessed for each technique. The limits of agreement for the differences in ejection fraction (%) between the two methods was--11.4, 12.2; the mean difference 0.4 was not significantly different from zero. The limits of agreement for the intra- and inter-observer differences in ejection fraction by radionuclide ventriculography were--9.4, 7.6 and -8.6, 11.0, respectively; the mean differences--0.9 and 1.2 were not significantly different from zero. The limits of agreement for the intra- and inter-observer differences by echocardiography were--5.8, 6.6 and--8.9, 9.5 respectively; the mean differences 0.4 and 0.3 were not significantly different from zero. Thus, two-dimensional echocardiography compares well with radionuclide ventriculography for the assessment of ejection fraction without the disadvantage of radiation. PMID- 7982425 TI - Improvement in identification of multivessel disease after acute myocardial infarction following stress-recovery analysis of ST depression in the heart rate domain during exercise. AB - The demonstration of extensive coronary artery disease (CAD) after acute myocardial infarction (AMI) has important prognostic implications. Exercise induced ST segment depression is commonly used for detecting the presence of CAD and evaluating its extension. However, even though there have been many attempts to increase its diagnostic yield, the accuracy of the electrocardiographic signal for identifying multivessel disease (MVD) is relatively low, particularly in post MI patients. The aim of this study was to evaluate the ability of a simple index, combining information on the amount and kinetics of ST depression in the heart rate domain during exercise and recovery, to identify MVD after AMI. Seventy patients (mean age 53.4 years) underwent a bicycle, symptom-limited exercise stress test and coronary angiography 2-3 weeks and 6 weeks respectively, after uncomplicated AMI while cardioactive therapy was discontinued. After obtaining a computer-derived measurement of ST levels based on incremental averaging of normal complexes, the area subtended to baseline and limited by the ST trend against heart rate during both exercise (A1) and recovery (A2) was calculated. The difference (A1-A2) was defined as the 'Stress-Recovery Index' (SRI) and dichotomized, by means of receiver-operating characteristics curve analysis, at 5 mm x beats.min-1 to define an increased risk of MVD. The SRI of patients with MVD was significantly lower than that of patients with single vessel disease. The sensitivity of SRI < -5 mm x beats.min-1 (65%) for predicting MVD was significantly higher than that obtained by other conventional parameters, without appreciable loss of specificity (81%).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7982426 TI - A simple formula for the estimation of maximal oxygen intake during cycle ergometry. AB - Exercise prescription has traditionally been based on the heart rate/work rate relationship. Many post-myocardial (MI) patients are now taking medications such as beta-blockers that alter this relationship, necessitating an alternative method for exercise prescription. The directly measured maximal oxygen intake (VO2max) is not substantially affected by such medications, but direct determinations of VO2max are time consuming, costly, and vulnerable to both local muscle weakness and poor motivation. We have therefore re-examined the relationship between work rate and maximal oxygen intake in order to derive a simple formula which will give an indirect estimate of the latter. Our results, obtained on 28 patients receiving beta-blockers, 13 receiving calcium channel blockers, 10 receiving combined therapy, and 49 who received neither treatment, indicate that the peak oxygen intake can be estimated accurately, using the expression VO2max.ml.min-1 = 2W, where W is the peak power output, measured in kp.m.min-1, or 12.3 W, where W is the peak power output in Watts. PMID- 7982427 TI - Idiopathic verapamil-responsive left ventricular tachycardia: clinical characteristics and long-term follow-up of 33 patients. AB - Long-term prognosis, pharmacological prophylaxis and transcatheter ablation in a large group of patients with idiopathic verapamil-responsive left ventricular tachycardia (IVRLVT) are reported in this study. Thirty-three patients with a mean age of 27 +/- 16 years at their first IVRLVT episode, were studied retrospectively. Ventricular tachycardia was of the right bundle branch block morphology in all cases, with left axis deviation in 29 and right axis deviation in five (one patient had the two morphologies). Mitral valve prolapse was present in four patients; no heart disease was found in the remaining 29. Ventricular tachycardia could be electrophysiologically induced in 90% of the patients; Holter monitoring showed only sporadic ventricular extrasystoles in 76%; late potentials were found in 33% of the cases. At the end of a follow-up of 5.7 +/- 4.7 years, no patient had died. Thirty-one patients (94%) received a mean of 2.5 +/- 1.2 drugs; beta-blockers were effective in 71% of the cases, verapamil in 25%, class 1 drugs in 22%, class 3 drugs in 18%. Two patients who never received prophylaxis and four in whom it was stopped, were controlled with verapamil in case of recurrence. Six patients underwent catheter ablation; two with DC shock in whom it was successful in one, and four with radiofrequency energy, with a total success rate. The good prognosis of IVRLVT has been confirmed in a long term follow-up; a new finding is the high efficacy of beta-blockers for prophylaxis. Radiofrequency transcatheter ablation is an effective and safe therapy for patients with symptoms not controlled by drug treatment. PMID- 7982428 TI - Endothelial Gi protein in human coronary arteries. AB - Endothelium-dependent relaxations mediated by Gi protein are prominently impaired in atherosclerotic coronary arteries. However, it remains to be determined whether the expression of endothelial Gi protein per se is reduced in coronary atherosclerosis. Thus, in the present study the expression of endothelial Gi protein was examined by immunohistochemical staining using a specific antibody against human Gi protein (alpha-subunits of Gi-1 and Gi-2 proteins) in the proximal segment of the left anterior descending coronary arteries (segment 6) from 40 consecutive autopsy cases. The immunoreactive level of the Gi protein was semi-quantitated in four grades (none, 0; slight, +; moderate, +2; high, +3) and the mean value of the ratings of all endothelial cells was used as an index of the endothelial Gi protein expression of the artery. The immunoreactive level of the Gi protein in human coronary arteries was significantly reduced with ageing and extent of coronary atherosclerosis (both P < 0.05), and was lower in patients with than in those without hypertension (P < 0.01) or hyperlipidaemia (P < 0.05). In addition, the level was significantly lower in the eccentric portions than in the concentric ones in each atherosclerotic coronary artery (P < 0.0001). These alterations in the immunoreactive level of endothelial Gi protein in human coronary arteries may explain, in part, why Gi protein-mediated, endothelium dependent relaxations are prominently impaired in atherosclerosis. PMID- 7982429 TI - Efficacy of L-propionylcarnitine treatment in patients with left ventricular dysfunction. AB - The effect of L-propionylcarnitine on patients with left ventricular dysfunction (EF < 45%) NYHA class II, symptomatic despite therapy with digitalis and diuretics was evaluated in a phase II parallel, double-blind, randomized, placebo controlled study. Fifty patients (28 men and 22 women) aged 37-70 years received 1.5 g of L-propionylcarnitine or placebo on a random basis as oral treatment for 6 months. At baseline, during a 7 day placebo run-in period, and during the 6 month treatment bicycle exercise test, M-B mode and Doppler echocardiography, and clinical evaluation (clinical score) were repeatedly performed. The analysis of variance for repeated measurements showed a statistically significant difference (P < 0.01) in the mean value of exercise time between the treatments over the period of the study. There was a final increase of 0.36 min in the placebo group, 1.4 min in the treated group and a minor production of lactate during exercise in the treated group. Left ventricular shortening fraction and left ventricular ejection fraction showed a significant increase in the L-propionylcarnitine group (respectively P < 0.01 and P < 0.0001) whereas no difference was apparent in the placebo group. Stroke volume index and cardiac index showed significant increments in the treated group (P < 0.05) and systemic vascular resistance was lowered (P < 0.05). No haemodynamic variations were observed in the placebo group, and the clinical score showed a significant improvement in the L propionylcarnitine treated group. In conclusion, L-propionylcarnitine treatment was shown to improve patient symptomatology and effort tolerance. PMID- 7982430 TI - Single infusion of intravenous cibenzoline in the treatment of supraventricular tachyarrhythmias following heart surgery. A double-blind placebo-controlled parallel study. AB - The efficacy and safety of a single infusion of cibenzoline, a class I antiarrhythmic drug, were assessed in 86 patients presenting with a supraventricular tachyarrhythmia following heart surgery in a placebo-controlled double-blind parallel study. Cibenzoline was effective in 13 patients (30%) vs three patients (6.9%) with placebo (P < 0.05). In the non-converted patients, ventricular rate was significantly slowed by cibenzoline (P < 0.05), which also significantly increased the duration of QRS and QT intervals. Transient adverse events were seen in nine patients receiving cibenzoline: moderate hypotension, sweating, right bundle branch block. One patient with decreased left ventricular function had an increased ventricular rate and QRS duration associated with hypotension. There were no severe adverse events. These results suggest that cibenzoline is effective for the treatment of postoperative supraventricular tachyarrhythmias in patients without impairment of ventricular function. PMID- 7982431 TI - Embolic stroke after unanticoagulated cardioversion despite prior exclusion of atrial thrombi by transoesophageal echocardiography. AB - Recent studies in patients with atrial fibrillation, not on anticoagulation, suggest that if transoesophageal echocardiography (TEE) excludes the presence of thrombi, early cardioversion can be performed safely without the need for anticoagulation before the procedure. Immediately after successful cardioversion, however, left atrium or left atrial appendage stunning may be present, potentially carrying a risk for de novo thrombus formation. Furthermore, the presence of spontaneous contrast is considered as a contraindication for unanticoagulated cardioversion since it has been associated with postcardioversion thromboembolism. We present a case in which stroke developed in relation to unanticoagulated cardioversion regardless of careful prior evaluation with TEE. PMID- 7982432 TI - Massive pulmonary embolism in pregnancy treated with streptokinase and percutaneous catheter fragmentation. AB - Despite heightened awareness, pulmonary embolism remains a major cause of maternal mortality in the antenatal period and one which has not decreased in incidence over the four triennia since 1976. We report a patient who suffered massive pulmonary embolism with circulatory collapse in the second trimester and who was treated with intravenous streptokinase followed by percutaneous mechanical dispersion of thrombus using a catheter and guide wire. She made an excellent recovery despite complicating antepartum haemorrhage. In life threatening circumstances pharmacological thrombolysis is mandatory particularly for hospitals without a cardiac catheterization laboratory on site. PMID- 7982433 TI - Impending paradoxical embolism: a case report and literature review. AB - Paradoxical embolism occurs following the passage of embolic material from the venous to the arterial circulation through a right to left shunt--frequently a patent foramen ovale. The diagnosis is usually presumptive when arterial emboli occur in the appropriate clinical setting. We describe a case of impending paradoxical embolism in a patient with massive pulmonary embolism. Transoesophageal echocardiography revealed a thromboembolus straddling a patent foramen ovale. The patient underwent emergency removal of the intracardiac clot with closure of the patent foramen ovale. PMID- 7982434 TI - Dramatic improvement of severe dilated cardiomyopathy in an acromegalic patient after treatment with octreotide and trans-sphenoidal surgery. AB - Severe congestive heart failure developed in an acromegalic patient, and was successfully treated with octreotide followed by trans-sphenoidal surgery. Clinical, hormonal echocardiographic and haemodynamic findings as well as histological heart examination before and after treatment revealed that over production of growth hormone may induce the myocardial cell degeneration responsible for mechanical heart dysfunction. In addition, this unique example demonstrates the reversibility of myocardial damage following octreotide and trans-sphenoidal surgery, leading to significant improvement in cardiac function with minimal diastolic dysfunction and moderate interstitial fibrosis. PMID- 7982435 TI - Embolic complications in Multicenter European Radiofrequency Survey (MERFS) PMID- 7982436 TI - Helicobacter pylori. PMID- 7982437 TI - Group A streptococcal antigens and superantigens in the pathogenesis of autoimmune arthritis. AB - Evidence from repeated clinical observations and from a variety of experimental approaches implicates group A streptococci in the pathogenesis of the autoimmune arthritides. Several streptococcal antigens and superantigens have now been characterized and their properties suggest that they may be involved in the mechanisms which underlie these diseases, although other antigens and superantigens yet to be discovered may also be involved. The association between group A streptococcal infection and autoimmune arthritis offers a useful model for providing a long-elusive understanding of the role of bacterial infection in the pathogenesis of autoimmune disease. PMID- 7982438 TI - The roles of alpha-glucosidase inhibitors in diabetes. PMID- 7982439 TI - The lymphocyte Na+/H+ antiport and its activation by increased NaCl intake: the link with salt sensitivity and cellular Ca2+ regulation. PMID- 7982440 TI - The lymphocyte Na+/H+ antiport: activation in primary hypertension and during chronic NaCl-loading. AB - Increased activity of the Na+/H+ antiport may be a major abnormality in essential hypertension. The activity of this transport system was investigated in lymphocytes from 13 patients with untreated essential hypertension (Ht) and 13 normotensive control subjects (Nt) on an ad libitum (130-170 mmol d-1) NaCl intake. Furthermore, the effects of different states of NaCl balance on lymphocyte Na+/H+ antiport were evaluated in two groups of Nt volunteers receiving 20 vs. 300 mmol d-1 (n = 8) and 85 vs. 200 mmol d-1 (n = 14) of NaCl for 1 week each and in seven Ht patients (20 vs. 300 mmol NaCl d-1 for 1 week each). Additionally, during the 20 and 300 mmol/d NaCl intake red blood cell membrane transport was studied in eight subjects. For the determination of lymphocyte antiport activity, cells were loaded with the cytosolic pH (pHi) indicator bis-carboxyethyl carboxyfluorescein (BCECF-AM) and acidified by addition of different amounts of Na(+)-propionate (5-40 mM). Initial pHi-recovery was taken as the activity of the antiport system and plotted against pHi-values after acidification. Non-linear regression analysis yielded higher 'apparent' maximal transport rates in Ht than Nt (Nt: 2.00 +/- 0.22; Ht: (3.81 +/- 0.59) x 10(-3) s-1; P < 0.025). In contrast, baseline pHi-values and pHi-values at half maximal activity (pK) were identical in Nt and Ht. In normotensive control subjects on an NaCl intake of 20, 85, 200 and 300 mmol d-1 for 7 d, 'apparent' maximal transport rates averaged 2.75 +/- 0.20, 2.89 +/- 0.17, 2.81 +/- 0.18 and (3.62 +/- 0.25) x 10(-3) s-1, respectively. Thus, antiport activity was significantly (P < 0.05) stimulated on the 300 mmol d-1 intake as compared to the three other NaCl intakes. The extreme intakes of NaCl (20 vs. 300 mmol d-1) in normotensive volunteers did not affect the erythrocyte Na+/K+ pump, Na+/K+ cotransport and Na+/Li+ countertransport. Our study supports the concept that a group of patients with primary hypertension exhibit an activated Na+/H+ antiport. Furthermore, our data demonstrate that a chronic high intake of NaCl is associated with an increase in lymphocyte antiport activity towards the high values observed in primary hypertension. PMID- 7982441 TI - Abdominal rubber drain piece aggravates intra-abdominal sepsis in the rat. AB - Biomaterials in the peritoneal cavity disrupt the physiology of the host and may cause bacterial translocation. The current study was performed to determine whether biomaterials exacerbate intra-abdominal infections. Adult male rats were divided into four groups: group 1, celiotomy+intraperitoneal (i.p.) saline; group 2, celiotomy+i.p. Escherichia coli (3 x 10(8) cfu); group 3, i.p. rubber+i.p. saline; and group 4, i.p. rubber+i.p. E. coli (3 x 10(8) cfu). Twelve h after the challenge, enteric bacterial translocation, bacterial population levels in the cecum and serum levels of IL-6 and TNF were measured. Bacterial translocation to mesenteric lymph nodes and the liver was observed in animals from groups 2 and 3, but significantly increased in group 4 with a concomitant elevation of serum levels of TNF and IL-6, as compared with group 1. Histological examination revealed a more pronounced inflammatory reaction in the peritoneum and distal ileum in group 4 than in groups 2 and 3. These results suggest that the presence of rubbers in the peritoneal cavity aggravates intra-abdominal sepsis. PMID- 7982442 TI - Distribution of hepatitis B virus DNA sequences in different peripheral blood mononuclear cell subsets in HBs antigen-positive and negative patients. AB - Hepatitis B virus (HBV) DNA sequences have been detected in leucocytes from HBV infected individuals. The aim of this study was to assess the specificity of HBV for a special leucocyte subset in nine healthy chronic HBV carriers, nine HBs antigen-positive patients with chronic active hepatitis, 16 HBs antigen-negative haemophiliacs with HBc and/or HBs antibodies, and 10 patients with HBV-related systemic necrotizing vasculitis. HBV-DNA sequences were found by Southern blot hybridization in the leucocytes of 15 out of the 44 (34%) patients. The prevalence was not significantly different between the four groups. HBV-DNA was found in the CD4+ cells (9/11) as well as in the CD8+ cells (4/11), B cells (4/12) and monocytes (2/12). In conclusion, leucocytes, and particularly CD4+ lymphocytes, are frequently infected by HBV in patients with HBV serum markers. PMID- 7982443 TI - Inter-relations between the calcium set-points of Parfitt and Brown in primary hyperparathyroidism: a sequential citrate and calcium clamp study. AB - The objective of the present study was to compare the calcium set-points of E. M. Brown and A. M. Parfitt obtained by sequential citrate and calcium clamp in patients with primary hyperparathyroidism and healthy controls. Twenty-six patients with primary hyperparathyroidism were investigated and compared to 22 healthy volunteers. All participants were investigated by sequential calcium lowering and raising comprising the following four phases: Phase (1) blood ionized calcium lowering of about 0.20 mmol l-1; phase (2) steady-state (relative) hypocalcaemia of blood ionized calcium 0.20 mmol l-1 below baseline; phase (3) blood ionized calcium is raised to about 0.20 mmol l-1 above baseline; and phase (4) (relative) hypercalcaemia of blood ionized calcium 0.20 mmol l-1 above baseline. Serum parathyroid hormone (1-84) was measured by an immunoradiometric assay. Blood ionized calcium was measured by a calcium selective electrode. We found the calcium set-points of Parfitt to be 1.42 mmol l 1 (SD 0.12, n = 52) vs. 1.25 mmol l-1 (SD 0.04, n = 44) in patients and controls, respectively (P < 0.001). The calcium set-points of Brown were 1.32 mmol l-1 (SD 0.10, n = 26) vs. 1.13 mmol l-1 (SD 0.04, n = 22), respectively (P < 0.001). By comparing the calcium set-points of Parfitt and Brown, a strikingly good correlation was observed, in patients (r = 0.91, P < 0.001) and in controls (r = 0.85, P < 0.001). We demonstrate in this paper in vivo that Brown's and Parfitt's calcium set-points are raised in primary hyperparathyroidism and return to normal following parathyroidectomy.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7982444 TI - Cognitive brain function in non-demented patients with low-grade and high-grade carotid artery stenosis. AB - Atherosclerotic stenosis of the carotid arteries decreases cerebral flow volume and perfusion, and may result in brain dysfunction. We studied the relationship between the degree of carotid artery stenosis and cognitive brain function in non demented patients. Cognitive brain function was assessed in 76 patients with carotid artery stenosis (38 patients with low-grade stenosis of 50% or less, and 38 patients with high-grade stenosis of 75% or more) by recording of cognitive P300 auditory evoked potentials and trailmaking test. Results were compared to 70 age-matched healthy subjects. The P300 peak latency was prolonged in patients with high-grade carotid artery stenosis as compared to patients with low-grade stenosis (403 vs. 371 ms, P < 0.01, vertex; 400 vs. 370 ms, P < 0.01, frontal; means). Analysis of variance revealed that the degree of carotid artery stenosis is an independent predictor of prolonged P300 peak latency (P = 0.0001). P300 amplitude (12 vs. 15 microV, vertex; 13 vs. 15 microV, frontal, NS) and trailmaking test (60 vs. 54 s; NS) tended to be worse in the high-grade stenosis group. There was no difference in cognitive brain function between patients with low-grade stenosis and age-matched healthy subjects. Confirmed on sensitive cognitive P300 measurements, we conclude that (a) cognitive brain function is impaired in non-demented patients with high-grade carotid artery stenosis but unaffected in low-grade stenosis; and (b) cognitive brain dysfunction is directly related to the degree of carotid artery stenosis. PMID- 7982445 TI - A 5-year controlled randomized study of prevention of postmenopausal trabecular bone loss with nasal salmon calcitonin and calcium. AB - The aim of this paper was to evaluate the long-term (5 years) efficacy of nasal salmon calcitonin in prevention of trabecular postmenopausal bone loss, which was a follow-up of a previously published study (3 years); a randomized, controlled group comparison. One hundred healthy postmenopausal women were randomly chosen from those (186) having completed the 3 year protocol. The 100 women were allocated to an additional 2 year period (total of 5 years) of treatment with either 500 mg d-1, 5 days week-1 of calcium or the same amount of calcium plus 50 IU d-1, 5 days per week of nasal salmon calcitonin, 87 (87%) women complied with the protocol throughout. The main outcome measures were the bone mineral density of the lumbar spine (1-BMD) (DPA) and biochemical parameters reflecting bone turnover (serum alkaline phosphatases, urinary calcium/creatinine and hydroxyproline/creatinine ratios). The women receiving calcium alone presented a significant decrease in 1-BMD after 6 months [-1.6 (0.5)%] [mean(SEM)] (P < 0.01) and this decrease remained significant after 36 months [-6.1(0.8)%] (P < 0.01) and until the end of the trial [-6.6(1.0)% at t60] (P < 0.01). In women receiving calcium and calcitonin, 1-BMD significantly increased after 36 months [+2(0.7%] (P < 0.01) and 42 months [+2.5(0.7)%] (P < 0.01 and was unchanged at the other times of investigation [+1.1 (1.1)% at t60] (NS). The evolution of BMD in the two groups was highly significantly different (P < 0.001) since the sixth month of the study and remained so until the end of the study.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7982446 TI - The action of synthetic cannabinoids on the induction of long-term potentiation in the rat hippocampal slice. AB - Incubation of rat hippocampal slices with the synthetic cannabinoid (-)-11-OH delta 8-dimethylheptyl tetrahydrocannabinol (HU-210) (100 nM) prevented the induction of long-term potentiation of field excitatory postsynaptic potentials recorded in the CA1 region. However, in slices incubated with its non psychoactive (+)-isomer HU-211 (100 nM), which is reported to be an NMDA receptor antagonist, high frequency stimulation evoked a long-lasting potentiation, comparable to control slices. PMID- 7982447 TI - Glibenclamide selectively blocks ATP-sensitive K+ channels reconstituted from skeletal muscle. AB - Glibenclamide, a blocker of ATP-sensitive K+ (KATP) channels, was tested on three different types of rat skeletal K+ channels incorporated into bilayers. Glibenclamide (10 microM) blocked a class of KATP channels (unitary conductance of 57 pS in symmetric 150 mM KCl), which were inhibited by ATP. High concentrations of glibenclamide (100 microM) had no effect on either voltage gated K+ channels (37 pS), or Ca(2+)-activated K+ channels (210 pS). Our results show that glibenclamide, even at high concentrations (100 microM) that may be required for quick action in whole muscle experiments, is a selective and specific blocker of skeletal KATP channels. PMID- 7982448 TI - Inhibition by imidazoline and imidazolidine derivatives of glibenclamide sensitive K+ currents in Xenopus oocytes. AB - The effects of imidazoline and imidazolidine derivatives on glibenclamide sensitive K+ currents induced by the novel K+ channel opener, Y-26763 ((+) (3S,4R)-4-(N-acetyl-N-benzyloxyamino)-6-cyano-3,4-dihydro-2,2 -dimethyl-2H-1 benzopyran-3-ol), were investigated in voltage-clamped follicle-enclosed Xenopus oocytes. Of 14 imidazoline derivatives and seven imidazolidine derivatives tested, phenotalmine, (-)-cibenzoline, (+)-cibenzoline, alinidine, oxymetazoline, antazoline, midaglizole, xylometazoline, tramazoline and ST91 (2-(2,6 diethylphenylamino)-2-imidazoline hydrochloride) potently suppressed Y-26763 induced K+ currents (IC50 < 80 microM). The compounds which lack an aromatic ring in their structure, 2-methyl-2-imidazole and 2-hydrazino-2-imidazoline, did not affect the K+ currents. Clonidine and idazoxan, which both bind to imidazoline preferring binding sites with high affinity in various tissues, showed only a small inhibitory effect on Y-26763-induced K+ currents (IC50 780 microM and 955 microM, respectively). The non-imidazoline/non-imidazolidine alpha-adrenoceptor antagonists, WB-4101 (2-(2,6-dimethoxy-phenoxyethyl)-aminomethyl-1,4-benzodioxane hydrochloride), yohimbine and rauwolscine, showed suppressive effects on Y-26763 induced K+ currents (IC50 203 microM, 813 microM and 832 microM, respectively). Octopamine (1 mM), a non-imidazoline/non-imidazolidine alpha-adrenoceptor agonist, was inactive. The results suggest that (1) an aromatic ring or aromatic rings are an essential moiety for imidazoline or imidazolidine derivatives to block glibenclamide-sensitive K+ currents in oocytes, and (2) the K+ current blocking ability of imidazolines and imidazolidines is related to the alkylation of the benzene ring and the existence of a tertiary amine structure. The K+ current-blocking effects of imidazolines or imidazolidines may not be mediated by alpha-adrenoceptors, at least in follicle-enclosed Xenopus oocytes. PMID- 7982449 TI - Effect of DP-1904, a thromboxane A2 synthetase inhibitor, on crescentic nephritis in rats. AB - The antinephritic effect of DP-1904 [6-(1-imidazolylmethyl)-5,6,7,8 tetrahydronaphthalene-2-carboxylic acid hydrochloride], a thromboxane A2 synthetase inhibitor, was compared with that of OKY-046, using an experimental model of nephritis, crescentic-type anti-glomerular basement membrane nephritis. Test drugs were given p.o. once daily from the day after the the development of glomerular alteration as well as the elevation of proteinuria and plasma cholesterol. On the other hand, OKY-046 (20 mg/kg per day), a thromboxane A2 synthetase inhibitor, significantly inhibited only deterioration in the glomeruli. DP-1904 and OKY-046 inhibited glomerular thromboxane B2 production and increased glomerular prostaglandin E2 and 6-keto prostaglandin F1 alpha production in normal and nephritic rats. Both drugs inhibited the increase in platelet aggregability, restored decreased renal tissue blood flow to a near normal level and decreased the deposition of rat immunoglobulin G on glomerular basement membrane in nephritic rats. These results suggest that DP-1904 may be an effective agent for the treatment of proliferative glomerulonephritis. PMID- 7982450 TI - Evaluation of deprenyl for cocaine-like discriminative stimulus effects in rats. AB - The antiparkinsonian agent l-deprenyl is metabolized to l-methamphetamine and l amphetamine and, at higher doses, can facilitate the release and inhibit the reuptake of dopamine. Since l-deprenyl can affect dopamine release and reuptake it was important to evaluate it for cocaine-like discriminative stimulus effects. Male Fisher rats were trained to discriminate cocaine (10 mg/kg, i.p.) from saline in a two-lever, operant-conditioning procedure using schedules of food delivery or stimulus-shock termination. l-Deprenyl (17 mg/kg, i.p.) produced full generalization to cocaine under the food-delivery schedule but this or higher doses produced only partial generalization to cocaine under the stimulus-shock termination schedule. d-Deprenyl produced full generalization to cocaine under both schedules at i.p. doses of 5.6 to 10 mg/kg. These cocaine-like discriminative stimulus effects occur only at doses that are well above the clinically relevant dose range for l-deprenyl. PMID- 7982451 TI - Effect of maturation on airway plasma exudation induced by eicosanoids in guinea pig. AB - Airway reactivity to bronchoconstrictor mediators changes with age. We studied the effects of maturational change on airway responses induced by a thromboxane A2 mimetic, U-46619 (2, 6 and 20 nmol/kg; i.v.), leukotriene D4 (0.6 and 2 nmol/kg; i.v.) or vehicle (0.9% NaCl; i.v.) in immature (196 +/- 3 g: 2 weeks) and adult guinea pigs (512 +/- 5 g: 11 weeks). In the same animals, we measured both lung resistance (RL) to monitor airflow obstruction and extravasation of Evans Blue dye (20 mg/kg) to quantify airway plasma exudation. For a comparison, changes in RL in response to acetylcholine (5, 15 and 50 nmol/kg; i.v.) were also examined in both age groups. The order of potency to induce an increase in RL did not change with age (leukotriene D4 > U-46619 > acetylcholine). In immature animals, the peak RL after U-46619 (2, 6 and 20 nmol/kg; P < 0.05, P < 0.005 and P < 0.01, respectively) and leukotriene D4 (2 nmol/kg; P < 0.01) was significantly higher than in adult animals. U-46619 and leukotriene D4 produced significant extravasation of Evans Blue dye in both immature and adult animals. The order of potency to induce extravasated dye also did not change with age (leukotriene D4 > U-46619). The amount of extravasation of Evans Blue dye after U 46619 (6 and 20 nmol/kg) and leukotriene D4 (0.6 and 2 nmol/kg) was significantly smaller in immature animals than adults at all airway levels.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7982452 TI - Cardiovascular effects of mastoparan B and its structural requirements. AB - Mastoparan B is a cationic, amphiphilic tetradecaeptide (LKLKSIVSWAKKVL-CONH2) isolated from the venom of the hornet Vespa basalis. Intravenous injection of the peptide into rats caused a profound depression of blood pressure and cardiac function, which was inhibited by cyproheptadine, reserpine and multiple doses of compound 48/80, but not by diphenhydramine and cromolyn. Mastoparan from Paravespula lewisii showed little cardiovascular inhibitory activity. A synthetic mastoparan B analog in which lysine at position 2 was replaced by asparagine showed a marked decrease in the cardiovascular depressor effects, while replacing lysine at position 4, 11 or 12 with leucine did not cause a significant reduction in these effects. Replacing lysine at position 12 with leucine even caused a more sustained depressor effect. However, the analog in which lysines at positions 11 and 12 were replaced by leucine lost its cardiovascular inhibitory activity. Replacing tryptophan at position 9 with phenylalanine in mastoparan B did not affect its activity. It is concluded that mastoparan B is involved in the cardiovascular disturbances induced by the hornet venom. Lysine at position 2 is a critical residue for the cardiovascular effects of mastoparan B. A peptide molecule with two lysine residues, one located close to the amino terminus and the other near the carboxyl end of the peptide, appears to be the optimal structure for eliciting the cardiovascular depressor effects. PMID- 7982453 TI - The somatostatin analogue octreotide protects against ethanol-induced microcirculatory stasis and elevated vascular permeability in rat gastric mucosa. AB - Somatostatin 14 and various derivatives protect rat gastric mucosa against ethanol-induced lesions. Their mechanism of action is unknown. We investigated the effect of two somatostatin derivatives, octreotide and 5-(L)-citrullin octreotide, on ethanol-induced hemorrhagic lesions, microcirculatory stasis and elevated vascular permeability in the rat stomach, with the goal to elucitate the pharmacological and microcirculatory mechanisms behind the gastroprotective effect. Radioligand studies revealed a high affinity of octreotide for the somatostatin receptor (IC50 = 5 x 10(-10) mol/l), in contrast to 5-(L)-citrullin octreotide (IC50 = 3 x 10(-6) mol/l). This was in good agreement with the inhibition of growth hormone release from rat anterior pituitary cells (octreotide: IC50 = 1.2 x 10(-10) mol/l; 5-(L)-citrullin-octreotide: IC50 = 3 x 10(-6) mol/l). Intragastric administration of ethanol to rats resulted in lesions of the gastric mucosa affecting 18.9 +/- 3.1% of the area of the glandular stomach. Octreotide reduced the area to 6.4 +/- 1.7% (P < 0.05). The dose response curve was bell-shaped. 5-(L)-citrullin-octreotide was totally devoid of any protective activity (dose range: 0.1 ng/kg to 0.1 mg/kg). We further investigated the effect of the two peptides on ethanol-induced microcirculatory stasis and elevated vascular permeability. Ethanol in a concentration of 50% induced an increase in microvascular permeability, measured by the extravasation of the tracer fluorescein-isothiocyanate-dextran (molecular weight 150,000). Pretreatment with octreotide (0.1 ng/kg s.c.) prevented stasis and reduced capillary permeability significantly. 5-(L)-citrullin-octreotide had no effect on ethanol-induced microcirculatory stasis and elevated vascular permeability in rat gastric mucosa.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7982454 TI - Sex differences in nitric oxide-mediated attenuation of vascular reactivity to vasopressin are abolished by gonadectomy. AB - In the rat thoracic aorta, contractile responses to vasopressin are two-fold higher in females than in males, primarily because nitric oxide-mediated attenuation of contraction is greater in males than in females. To determine the role of the gonadal steroids in this phenomenon, the effects of gonadectomy on nitric oxide and vascular reactivity to vasopressin were examined in thoracic aortae of age-matched intact and gonadectomized male and female rats. Maximal response to vasopressin was markedly higher in gonadectomized-male than in intact male aortae (2729 +/- 421 vs. 1375 +/- 222 mg/mg ring weight; P < 0.01). Inhibition of nitric oxide synthase with NG-methyl-L-arginine (L-NMMA, 250 microM) enhanced maximal response of intact-male (2824 +/- 413 mg/mg ring weight; P < 0.01) but not gonadectomized-male aortae (3034 +/- 365 mg/mg ring weight; P > 0.05). Sensitivity of male aortae to vasopressin was unaffected by gonadectomy or L-NMMA. Maximal contraction to vasopressin did not differ between gonadectomized female and intact-female aortae (4003 +/- 180 vs. 4645 +/- 212 mg/mg ring weight; P > 0.05). L-NMMA increased the sensitivity but not the maximal response to vasopressin in intact-female and gonadectomized-female aortae. In contrast, maximal response to phenylephrine was similar in gonadectomized-male and intact male aortae (3843 +/- 175 vs. 4234 +/- 206 mg/mg ring weight; P > 0.05); L-NMMA enhanced maximal tension more in gonadectomized-male than in intact male aortae (4645 +/- 206 vs. 4612 +/- 176 mg/mg ring weight). Maximal contraction to phenylephrine was substantially higher in gonadectomized-female than in intact female aortae (4303 +/- 104 vs. 3341 +/- 155 mg/mg ring weight; P < 0.001); L NMMA enhanced maximal tension more in intact-female than in gonadectomized-female aortae (5073 +/- 158 vs. 4788 +/- 140 mg/mg ring weight). These results strongly suggest that the gonadal steroids exert important regulatory effects on nitric oxide release in the rat aorta, which are vasoconstrictor-specific and appear to involve basal and/or agonist-stimulated nitric oxide release. PMID- 7982455 TI - Effects of chronic receptor blockade on excitation-contraction coupling in rat aortic rings. AB - The effects of an intracellular Ca2+ depletor (ryanodine), a Ca2+ channel antagonist (felodipine), a protein kinase C inhibitor (staurosporine) as well as caffeine, cholera and pertussis toxin have been examined on noradrenaline-induced contractions in aortic rings from rats pretreated i.v. with either saline or phenoxybenzamine for 7 days. Ryanodine (3 and 10 microM) was able to both potentiate and inhibit noradrenaline-evoked contractions in aortic rings from phenoxybenzamine-treated rats. However, ryanodine did not affect the concentration-response curves to noradrenaline in tissues from saline-treated rats. Further, felodipine (1 and 10 nM) and staurosporine (10 nM) inhibited noradrenaline-induced contractions in aortic rings from phenoxybenzamine- but not saline-treated rats. Pertussis toxin (100 ng/ml) also inhibited contractions produced by noradrenaline in rings from phenoxybenzamine- but not saline-treated rats. In contrast to these observations, both caffeine (1 mM) and cholera toxin (3 micrograms/ml) inhibited noradrenaline-evoked contractions in aortic rings from phenoxybenzamine- and saline-treated rats. The results suggest that chronic receptor blockade by phenoxybenzamine leads to alteration in alpha-adrenoceptor mediated signal transduction in the aorta. The changes include alteration in Ca2+ handling at the plasmalemmal and intracellular levels, as well as an altered action of pertussis toxin-sensitive G-protein, but not of cholera toxin-sensitive G-protein. PMID- 7982456 TI - P2 purinoceptor antagonist properties of pyridoxal-5-phosphate. AB - The antagonist properties of pyridoxal-5-phosphate, a synthesis precursor of pyridoxalphosphate-6-azophenyl-2',4'-disulphonic acid, were investigated on P2 purinoceptor-mediated responses of the rat isolated vagus nerve and vas deferens. In addition, the effect of this agent was studied on high affinity tritiated alpha,beta-methylene adenosine triphosphate (alpha,beta-meATP) binding to rat vas deferens membranes, thought to represent binding to functional P2x purinoceptors. In the rat vagus nerve, pyridoxal-5-phosphate (10(-5)-10(-4) M) produced concentration-related antagonism of depolarisation responses induced by alpha,beta-meATP, measured using an extracellular recording technique. In contrast, depolarisation responses to 5-hydroxytryptamine (5-HT) were unaffected by pyridoxal-5-phosphate. In the rat vas deferens, pyridoxal-5-phosphate (10(-5) 10(-4) M) antagonised contractile responses produced by alpha,beta-meATP while contractions to phenylephrine were unaffected. However, responses of the vagus nerve and the vas deferens to alpha,beta-meATP were not antagonised by pyridoxal hydrochloride (10(-4) M). Pyridoxal-5-phosphate competed for high affinity binding of [3H]alpha,beta-meATP to homogenised membranes of the rat vas deferens with a pKi estimate of 4.91 +/- 0.12 and a Hill slope of 0.80 +/- 0.03. Pyridoxal hydrochloride only competed for binding at concentrations in excess of 10(-4) M, yielding a pKi estimate of 3.21 +/- 0.04 and a Hill slope of 1.82 +/- 0.12. These findings indicate that pyridoxal-5-phosphate acts as a specific antagonist of P2 purinoceptors in the vagus nerve and vas deferens of the rat and that the phosphate moiety is required for activity.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7982457 TI - Dopamine D1 receptor agonist-induced grooming is blocked by the opioid receptor antagonist naloxone. AB - The effects of the opioid receptor antagonist naloxone on behavioural responses to the dopamine D1 receptor agonist SKF 38393 ((+/-)-1-phenyl-2,3,4,5-tetrahydro (1H)-3-benzazepine-7,8-diol hydrochloride) were assessed in the rat. SKF 38393 (5 mg/kg s.c.) induced grooming and vacuous chewing mouth movements. SKF 38393 induced grooming was dose-dependently attenuated by naloxone (0.375-1.5 mg/kg s.c), while vacuous chewing movements were unaffected. These findings suggest that dopamine D1 receptor agonist-induced grooming is dependent upon opioid systems, while vacuous chewing movements are likely to be mediated via different pathways. PMID- 7982458 TI - Central sympathetic control of spinal endothelin release in the rat. AB - Endothelin and its receptors have been identified in the spinal cord. Intrathecal administration of endothelin-3 produces hypotension in anesthetized rats. The present study was designed to identify whether endothelin-3 is released upon changes in sympathetic nervous activity. Endothelin-3-like immunoreactivity in spinal superfusates was directly correlated with resting arterial pressure. Endothelin-3 levels were enhanced by hypothalamic stimulation and by hemorrhage induced hypotension and reduced by nitroprusside-induced hypotension. These findings suggest that sympathetic activation enhances endothelin-3 release but that nitroprusside may act directly to suppress release. We propose that endothelin-3 plays a role in spinal regulation of sympathetic outflow. PMID- 7982459 TI - Effects of bradykinin receptor agonists, and captopril and thiorphan in ferret isolated trachea: evidence for bradykinin generation in vitro. AB - Bradykinin B2 receptor agonists, but not a B1 receptor agonist, were potent spasmogens of ferret isolated trachea. Bradykinin-induced contractions were unaffected by several pharmacological agents, indicating a direct effect on airway smooth muscle B2 receptors. Captopril plus thiorphan caused contractions in approximately 70% of preparations that were abolished by B2 receptor antagonists, but not by B1 receptor antagonist. Thus, ferret tracheal tissues appear capable of releasing and degrading kinins in vitro. Inhibition of peptide degradation with captopril and thiorphan may allow the endogenous kinins to accumulate in concentrations sufficient to elicit tracheal contraction via activation of B2 receptors. PMID- 7982460 TI - EP3 receptor-mediated inhibition of the neurogenic vasopressor response in pithed rats. AB - In pithed rats, we studied the effects of prostaglandin E2 and of subtype selective prostaglandin E receptor (EP receptor) ligands on the rise in blood pressure induced by electrical stimulation of the preganglionic sympathetic nerves. Prostaglandin E2, the EP1/EP3 receptor agonist sulprostone and the EP2/EP3 receptor agonist misoprostol inhibited the electrically induced increase in diastolic blood pressure (rank order of potencies sulprostone > or = misoprostol > or = prostaglandin E2); the rise in blood pressure induced by exogenously added noradrenaline was not affected by these compounds. The inhibitory effect of sulprostone on the electrically induced vasopressor response was not significantly changed by indomethacin. Iloprost (an agonist at EP1 and prostacyclin receptors (IP receptors)) failed to affect the electrically evoked increase in blood pressure. The present study suggests that prostaglandin E2 inhibits the release of catecholamines in pithed rats via prostanoid receptors of the EP3 subtype, probably located presynaptically on the postganglionic sympathetic nerve fibres. PMID- 7982461 TI - Decrease in vasodilator effects of platelet-activating factor in resistance vessels of spontaneously hypertensive rats. AB - We studied the endothelium-dependent vasodilator effects of platelet-activating factor (PAF) on the mesenteric arterial bed of Wistar Kyoto rats (WKYs) and spontaneously hypertensive rats (SHRs) and found that vasodilation induced by PAF was significantly attenuated in SHRs. We discovered no significant differences in reactivity or sensitivity of the mesentery to acetylcholine between WKYs and SHRs. Our results strongly suggest that the attenuated vasodilator effects of PAF on the SHR mesenteric arterial bed may be due in part to desensitization rather than impairment of the endothelium. PMID- 7982462 TI - V1-like [Arg8]vasopressin binding sites occur in rat hepatocyte nuclei. AB - Arginine vasopressin binding site characterisation was performed on purified nuclei and plasma membranes from livers of Sprague-Dawley rats. [125I][d(CH2)5,Sarc7,Arg8]vasopressin, a selective V1 vasopressin receptor antagonist radioligand, bound to the nuclei in a protein concentration and time dependent manner. Scatchard analysis of nuclear binding sites revealed a single binding site with maximal binding site density (Bmax) of 115 +/- 13 fmol/mg protein and affinity (KD) of 5.2 +/- 0.7 nM. Plasma membrane binding demonstrated a Bmax of 529 +/- 25 fmol/mg protein and KD of 1.9 +/- 0.1 nM. The displacement profile for nuclear binding sites using vasopressin analogues was similar to that for plasma membrane binding sites and was typical of a V1 vasopressin receptor type. There was no evidence of V2-like vasopressin receptor binding using [3H]des Gly-NH9(2)[d(CH2)5,D-Ile2,Ile4,Arg8]vasopressi n, a selective V2 vasopressin receptor radioligand, in the nuclear or membrane fractions. These results suggest the existence of nuclear V1-like vasopressin binding sites. PMID- 7982463 TI - Beta-funaltrexamine blockade of opioid-induced inhibition of somatostatin secretion from rat stomach. AB - Opioid peptides are potent inhibitors of gastric somatostatin secretion. In the current investigation the effect of mu-opioid receptor blockade on responses to [D-Ala2,N-Me-Phe4,Gly5-ol]enkephalin (DAGO) was studied. Gastric inhibitory polypeptide (GIP; 1 nM) -stimulated secretion of immunoreactive somatostatin was almost completely inhibited by DAGO (1 microM). The mu-receptor antagonists, beta funaltrexamine and naloxonazine, blocked the effect of DAGO. Pretreatment of rats with beta-funaltrexamine, 24 h prior to perfusion, reduced the percentage inhibition by DAGO from 88.6 +/- 5.2% to 50.7 +/- 9.3%. These studies support the involvement of mu-opioid inhibitory receptors in the regulation of gastric somatostatin secretion. PMID- 7982464 TI - Inhibition of human IsK channels expressed in Xenopus oocytes by calmodulin antagonists. AB - The calmodulin antagonists, trifluoperazine, chlorpromazine and W7 (10-[3-(4 methyl-1-piperazinyl)-propyl]-2-(trifluomethyl)-10H-phen othiazine , 2-chloro-10 (dimethylaminopropyl)-phenothiazine and N-(6-aminohexyl)-5-chloro-1-naphtalen sulfonamide, respectively), were tested for their effects on human IsK channels expressed in Xenopus oocytes and their interference with the previously described [Ca2+]i-mediated regulation of IsK. An increase in [Ca2+]i accelerated IsK activation and increased the current amplitude, as has been previously observed. Chlorpromazine, trifluoperazine and W7 inhibited depolarization-activated IsK channels with an EC50 between 70 and 100 microM. None of the calmodulin antagonists abolished the regulation of IsK by A23187 (calcimycin) or hypotonic extracellular fluid, although the inhibitory effects of these compounds were also obvious after enhancement of [Ca2+]i. In conclusion, the calmodulin antagonists inhibit IsK at both physiological and enhanced [Ca2+]i. PMID- 7982465 TI - Antihypertensive effects of BQ-123, a selective endothelin ETA receptor antagonist, in spontaneously hypertensive rats treated with DOCA-salt. AB - We determined the antihypertensive effects of BQ-123 (cyclo(D-Trp-D-Asp-L-Pro-D Val-L-Leu-), sodium salt), a selective endothelin ETA receptor antagonist, in spontaneously hypertensive rats treated with deoxycorticosterone acetate-salt (DOCA-salt SHR). BQ-123 (1-30 mg/kg/h) decreased blood pressure in DOCA-salt SHR in a dose-dependent manner, although plasma immunoreactive endothelin-1 did not significantly increase and the maximal contractile response to endothelin-1 in the aorta significantly decreased as compared with values observed in age-matched SHR. These results suggest that endogenous endothelin-1 is involved in the maintenance of hypertension in DOCA-salt SHR, and that circulating endothelin-1 is not sufficient to reflect the physiological role of endothelin-1. PMID- 7982466 TI - PTH and PTH-rP elicit dissimilar retractile responses in murine MC3T3-E1 osteoblasts. AB - Parathyroid hormone (PTH) and PTH-related peptide (PTH-rP) bind to a common receptor and initiate second-messenger cascades that stimulate bone turnover and hypercalcemia. However, PTH is more potent than PTH-rP in inducing bone resorption and coupled bone metabolism in intact tissue, suggesting that these proteins elicit dissimilar postreceptor responses. We compared the effects of PTH and PTH-rP on osteoblastic retraction, an early event that must occur before the osteoclast can achieve access to the underlying bone mineral and begin resorption. MC3T3-E1 mouse osteoblasts were incubated in vehicle or 4.8 nM PTH or PTH-rP with or without 1 mM dibutyryl cAMP (Bt2cAMP). Morphologic changes were observed from 0 to 120 min. PTH caused marked retraction within minutes, which was not enhanced by Bt2cAMP. PTH-rP or Bt2cAMP induced slower, more modest retraction than PTH. The combined effect of PTH-rP plus Bt2cAMP was greater than that of PTH-rP, but less than that of PTH. PTH-rP and PTH had similar effects on cAMP generation. Thus, compared to PTH, PTH-rP induces less osteoblastic retractile response, exposing less bone surface to osteoclastic resorption. This may account for its lower hypercalcemic potency in vivo and contribute to its relative inability to stimulate coupled bone resorption and formation. PMID- 7982467 TI - Constitutive secretion of erythropoietin by human renal adenocarcinoma cells in vivo and in vitro. AB - The paraneoplastic syndrome of erythrocytosis is associated with a variety of neoplasms including renal adenocarcinoma, cerebellar hemangioma, and hepatoma. We now report the characterization of the biological and molecular features of an erythropoietin-secreting human renal adenocarcinoma, designated RCCEp+. Serial transplantation of the tumor in athymic mice resulted in a dramatic increase in hematocrit and serum erythropoietin concentration. Growth in vitro was accompanied by a constant rate of erythropoietin secretion. Karyotype analysis demonstrated several unusual features, including the absence of 3p deletions and near tetraploidy. Erythropoietin mRNA was demonstrated by Northern blot both in freshly excised tumor and in tumor cells growing in vitro. Erythropoietin secretion was constitutive and was not induced either by cobalt or hypoxia. Southern blot analysis revealed no rearrangement of the erythropoietin gene in the tumor. Interestingly, in situ hybridization demonstrated erythropoietin mRNA in only a small population of the tumor cells. Further studies of RCCEp+ should prove useful in elucidating the molecular basis for this paraneoplastic syndrome. PMID- 7982468 TI - Proliferating cell nuclear antigen bound to DNA synthesis sites: phosphorylation and association with cyclin D1 and cyclin A. AB - Evidence is presented that association of proliferating cell nuclear antigen (PCNA) with nuclear chromatin in human fibroblasts is related to the phosphorylation status of the protein. Using a hypotonic lysis procedure to extract the soluble form of PCNA, it has been shown that the remaining nuclear bound form, predominantly in S-phase cells, is highly phosphorylated. Cells in early G1, or in G2 + M phases, contain basal levels of the bound form of the protein that is only weakly phosphorylated. Using fractionated immunoprecipitation techniques, PCNA was found to be associated with cyclin A in both soluble and insoluble fractions. In contrast, association of PCNA with cyclin D1 was found in the soluble fraction, while no detectable levels were present in the insoluble fraction. Immunofluorescence labeling and flow cytometric analysis of the cell cycle distribution of cyclin D1 and cyclin A showed that, like PCNA, maximal levels of both proteins were bound to nuclear structures at the G1/S phase boundary. These results suggest that binding of PCNA to DNA synthesis sites occurs after phosphorylation. Association with cyclin D1 and cyclin A might occur in a macromolecular complex assembled at the G1/S phase boundary to drive activation of DNA replication factors. PMID- 7982469 TI - Polymerization of tubulin in apoptotic cells is not cell cycle dependent. AB - Prominent, specific tubulin structures were identified in human leukemic cells undergoing apoptosis following treatment with cytotoxic drugs. In order to determine whether tubulin reorganization was dependent upon the stage of the cell cycle at which apoptosis was induced, the human leukemic T-cell line CCRF-CEM was treated with cytotoxic doses of drugs known to arrest cells at different stages of the cell cycle. Apoptosis was confirmed by the detection of characteristic single and multiple nucleosome-sized fragments by agarose gel electrophoresis of isolated DNA. Cells were treated with vincristine, methotrexate, and dexamethasone, which have been shown to induce cell cycle arrest at G2-M, S phase, and G1, respectively. Treated and untreated cells were analyzed by immunocytochemistry for beta-tubulin or Ki-67 antigen (to confirm cell cycle phase) and scored for apoptotic morphology. Dual staining for cellular tubulin and DNA content, measured by flow cytometry, was used to confirm the stage at which the cycling cells arrested. Increased total cellular tubulin immunofluorescence was observed in treated compared to untreated cells. Our results indicate that CCRF-CEM cells undergo apoptosis (identified morphologically) at all stages of the cell cycle except mitosis. We conclude that the reorganization of cellular tubulin that we have observed in apoptotic cells is independent of the tubulin involvement in cell division and thus may be an integral part of the apoptotic process. PMID- 7982470 TI - The IGF-1-IGF-1 receptor system modulates myocyte proliferation but not myocyte cellular hypertrophy in vitro. AB - In preliminary experiments it was established that the hypertrophic and hyperplastic responses of neonatal cardiac myocytes in culture were associated with enhanced expression of IGF-1 and IGF-1 receptors in these cells. Therefore, to determine the role of IGF-1 receptors on myocyte growth, cells were exposed to antisense oligodeoxynucleotides to IGF-1 receptor mRNA and the effects of this intervention on DNA synthesis, nuclear mitotic division, and changes in the number of myocytes were measured. Moreover, the influence of this procedure on ANF induction and myocyte cell volume was examined. Inhibition of the formation of IGF-1 receptors on myocytes suppressed DNA replication, mitosis, and cell proliferation. In contrast, the antisense treatment did not alter the expression of ANF in myocytes or cellular hypertrophy. Finally, IGF-1 stimulated DNA synthesis in myocytes cultured in serum-free medium, without inducing cellular hypertrophy. In conclusion, ligand activation of IGF-1 receptors on myocytes appears to be coupled with cell proliferation, whereas myocyte cellular hypertrophy seems to be independent from this effector pathway. PMID- 7982471 TI - Molecular cloning of TPAR1, a gene whose expression is repressed by the tumor promoter 12-O-tetradecanoylphorbol 13-acetate (TPA). AB - We previously isolated a partial cDNA sequence, termed TPAR1 (TPA repressed gene 1), from a cDNA library constructed from C3H10T1/2 mouse embryo fibroblasts treated with TPA, using a differential screening procedure. (M.D. Johnson et al. Mol. Cell. Biol. 7, 2821-2829, 1987). In the present study, we have cloned two corresponding full-length 1.9- and 3.4-kb cDNAs of TPAR1 from murine cDNA libraries. Sequence analysis of these TPAR1 cDNAs revealed that they encode 89 and 93 amino acid polypeptides, respectively, with a putative leader sequence and show significant homology with the human cytokine interleukin-8 (IL-8) and its superfamily. Genomic DNA isolation and structural characterization provide evidence that the TPAR1 mRNAs are transcribed from a single gene with alternative splicing. TPAR1 mRNAs are expressed ubiquitously among adult mouse tissues as three major transcripts, 1.9, 3.4, and 6.5 kb, whose expression depends on the tissue type. The levels of TPAR1 mRNAs were markedly decreased in fibroblasts following TPA treatment and also in serum-deprived quiescent fibroblasts stimulated by serum. The levels of TPAR1 mRNAs were dramatically down-regulated in regenerating rat liver when compared to normal adult liver. In addition, there was no detectable expression of TPAR1 in three rat hepatoma cell lines and several transformed fibroblast cell lines. Thus, the TPAR1 gene is a new member of the cytokine IL-8 superfamily, whose expression is down-regulated in rapidly dividing cells. Further studies are required to determine whether it plays a negative role in controlling cell proliferation and tumorigenesis. PMID- 7982472 TI - Regulation of fibronectin by insulin-like growth factor-I in cultured rat thoracic aortic smooth muscle cells and glomerular mesangial cells. AB - We examined the regulation of fibronectin (FN) levels by insulin-like growth factor-I (IGF-I) in rat thoracic aortic smooth muscle cell (SMC) and glomerular mesangial cell cultures. IGF-I enhances FN levels in the culture media of the SMC and in the cell samples of the mesangial cells. It shows no effect on FN levels in the cell samples of the SMC and in the culture media of the mesangial cells. Modulation of IGF-I-induced FN levels by insulin was also examined. Insulin enhances FN levels in the culture media of the SMC but not in the cell samples. Insulin did not induce an increase in FN levels in either the mesangial cell samples or the culture media. No additive effect of FN levels was observed when the SMC were treated with insulin and IGF-I together. The effect of IGF-I on FN mRNA levels was assessed. IGF-I enhances SMC and FN mRNA levels, implying that acquisition of additional FN mRNA units accounts for the increase in FN levels. The effects of actinomycin D and cycloheximide on IGF-I-induced FN mRNA levels were also examined. Inhibition of the IGF-I-induced FN mRNA levels by actinomycin D and an increase of FN mRNA levels by cycloheximide suggest that IGF-I regulates FN mRNA synthesis at the transcriptional level. PMID- 7982473 TI - N-CAM and N-cadherin expression during in vitro chondrogenesis. AB - Mesenchymal cell condensation in chick limb bud occurs at embryonic stage 22 and is the starting event of chondrogenesis. Several mechanisms have been proposed to have an active role in the induction of this process. Among them the establishment of cell-cell contacts represents a key event. Here we have investigated the modulation of N-CAM and N-cadherin gene expression in an in vitro culture system which allows chondrocyte differentiation to proceed from condensation of prechondrogenic cells to hypertrophic chondrocytes and eventually to osteoblast-like cells. Both Northern and Western blots demonstrated that they were developmentally regulated in differentiating chondrocytes. Both cell adhesion proteins were detectable in prechondrogenic cells, increased during cell aggregation, became undetectable in hypertrophic chondrocytes, and resulted in reexpression during their maturation to osteoblast-like cells. The timing of appearance of N-cadherin and N-CAM suggests that N-cadherin initiates the in vitro cell condensation thereafter stabilized by N-CAM. In agreement with the above findings, the immunolocalization of these molecules in the cell aggregates revealed that N-CAM and N-cadherin appear, after 12 h of suspension culture, on the surface of all cells at the membrane regions participating in cell-cell contacts. At 72 h N-CAM became restricted to cells at the aggregate periphery, while N-cadherin was detected both in type II collagen-negative and -positive regions. At this time of culture, electron microscopy shows a number of cell-cell contacts at the perifery of the cell aggregates, while only a few of them were observed in the aggregate interior. The expression of N-CAM and type II collagen by chondrocytes was mutually exclusive and a sorting out between differentiating and nondifferentiating cells occurred. PMID- 7982474 TI - Cell cycle-dependent nuclear localization of exogenously added fibroblast growth factor-1 in BALB/c 3T3 and human vascular endothelial cells. AB - Previous studies have shown that the presence of a functional nuclear targeting sequence in the primary structure of fibroblast growth factor (FGF)-1 correlates with its activity as a mitogen, but not with its potential for inducing receptor tyrosine phosphorylation, suggesting the presence of a yet undefined function of FGF-1 as a nuclear protein. In the present study we have investigated the cytosolic and nuclear localization of exogenously added FGF-1. FGF-1-specific monoclonal antibodies were raised. By an extensive screening, highly specific antibody clones were isolated. For both BALB/c 3T3 and human umbilical vein endothelial (HUVE) cells, immunofluorescence studies performed with those clones delineated that during G1 stage of cell cycle, FGF-1 transits from cytosol to nucleus. This was followed by a shift to the perinuclear and juxtanuclear region just prior to the onset of S-phase in BALB/c 3T3 cells. Confocal microscopical examinations confirmed that the nuclear staining resides throughout the nuclear matrix with some enrichment at the envelope boundary and in the nucleoli. Immunoblot analysis of the fractionated BALB/c 3T3 cells that had been induced to proliferate by serum and pulsed with exogenous FGF-1 at various timings revealed that the incorporation of exogenous FGF-1 into cytosol took place constantly, whereas the nuclear translocation significantly increased after 5 h following stimulation of the quiescent cells. The cytosolic form of FGF-1 is indicated to be present in soluble cytosolic fraction rather than membrane-enveloped compartments, endosomes, by the microinjection of anti FGF-1 antibody to HUVE cells cultured in the presence of FGF-1. The data demonstrate that the exogenously added FGF-1 is constantly endocytosed and fractioned into the cytosol soluble compartment, whereas its nuclear localization is regulated at the nuclear translocation level and takes place preferably at late G1 phase of the cell cycle. PMID- 7982475 TI - Induction of apoptosis by the anti-tubulin drug colcemid: relationship of mitotic checkpoint control to the induction of apoptosis in HeLa S3 cells. AB - We have studied the relationship between apoptosis and drug-induced cell cycle perturbation in HeLa S3 cells when treated with the anti-tubulin drug colcemid. We found that at least two distinct mechanisms contributed to colcemid cytotoxicity and apoptosis. Continuous exposure to concentrations of colcemid sufficient to block cells at the mitotic checkpoint led to the appearance of apoptotic cells approximately one cell cycle after their initial accumulation in mitosis. Continuous exposure to concentrations sufficient to delay mitotic progression but insufficient to cause mitotic arrest, or pulse exposure to concentrations of colcemid sufficient to induce mitotic block, led to the generation of multipolar mitoses and genetically deficient hypodiploid daughter cells which underwent apoptosis while in interphase. The fact that aberrant spindle function delayed but did not block cells at the mitotic checkpoint indicates that the mitotic checkpoint senses the presence or absence of the spindle but not spindle abnormalities. In both mitotic and interphase cells, colcemid-induced apoptosis occurred after a period of cell cycle stasis during which cells failed to complete an initiated cell cycle. These results are discussed with reference to understanding the relationship between apoptosis and the regulation of cell cycle progression. PMID- 7982476 TI - Gradual selection of a cellular clone presenting a mutation at codon 179 of the p53 gene during establishment of the immortalized human breast epithelial cell line HMT-3522. AB - We studied the occurrence of a p53 mutation along passages stored as frozen vials during establishment of a nontumorigenic human mammary epithelial cell line HMT 3522. Mutations were identified by a PCR-SSCP approach using DNA as a template. The mutation, a nonconservative nucleotide substitution at codon 179 changing a histidine into an asparagine, appeared between passages 51 and 63 and was concommitant to a change in growth conditions. Cells were no longer grown on collagen coat and cell growth was not responsive to insulin, transferrin, or hydrocortisone anymore. To assess if the mutation was an early or a late event during cell line evolution we put a vial of cells frozen at passage 30 back into culture and tested for the appearance of a p53 mutation along newly produced passages. The same mutation (His to Asp at codon 179), as previously identified, reemerged between passages 48 and 52, thus indicating that the mutation was preexisting in passage 30 and gradually selected out because of the growth advantage it conferred. In order to gain in sensitivity we used a RFLP approach on PCR fragments which allowed us to detect the mutation as early as passage 44. Hence it took 14 passages (approx 50 cell doublings) for the mutated cells to become detectable and another 9 passages (33 generations) to overgrow the wild type component of the population. We calculated that the mutated cells acquired a growth advantage which allowed them to cycle 1.2 +/- 0.05 faster than wild type. Computer simulations were consistent with the mutation appearing at passage 20. PMID- 7982477 TI - Role of retinoblastoma gene product in p53-mediated DNA damage response. AB - The cellular response to DNA-damaging agents involves the activation of cell cycle checkpoints. Checkpoints provide a transient delay in cell cycle progression, presumably to allow time for the cell to repair the damage. A most important checkpoint, active in the G1 phase of the cell cycle, is mediated by the p53 tumor suppressor gene product. To investigate the role of downstream components of the cell cycle machinery in p53-mediated G1 arrest, the possible involvement of the RB gene product was examined. Rb and p53 proteins were studied by immunoprecipitation and Western blotting experiments in the presence and absence of DNA-damaging treatment. The phosphorylation status of Rb was altered following DNA damage in p53 wild-type cell lines, but was not altered in p53 mutant cell lines, nor in cell lines where p53 function was abrogated by viral gene products. These findings indicate that Rb probably plays a role in the activation of the p53-mediated checkpoint. PMID- 7982478 TI - Direct evidence for tension development between flagellar doublet microtubules. AB - In this study of isolated ribbons of flagellar doublet microtubules, we demonstrate that a resistance to sliding exists in the interdoublet gap. By photolytically releasing ATP from caged ATP, it has been possible to follow closely the responses of individual specimens. Distortion of the helical superstructure of the doublets, most often by a reduction in helical pitch, is interpreted as revealing the development of tension between doublets. Tension does not develop in the presence of vanadate. PMID- 7982479 TI - Extracellular annexin VI expression is associated with divalent cation-dependent endothelial cell adhesion of metastatic RAW117 large-cell lymphoma cells. AB - We previously found that cell surface molecules of approximately 70, approximately 35, approximately 32, approximately 22, and approximately 14 kDa from liver-metastatic murine RAW117 large-cell lymphoma cells bound to target liver microvessel endothelial cells. Isolation and sequencing of the approximately 35-kDa component revealed it to be annexin II, a Ca(2+)-binding molecule involved in cytoskeletal and membrane interactions. Annexin II antibodies inhibited the adhesion of RAW117 tumor cells to live or fixed liver endothelial cells, and purified tumor cell surface fractions containing the approximately 35-kDa component inhibited partially RAW117 cell-endothelial cell adhesion, suggesting a role for annexins in tumor cell-endothelial cell adhesion. In the present study we identified the 70-kDa cell surface component that binds to hepatic sinusoidal endothelial cells in a Ca(2+)-dependent manner as annexin VI. Cytofluorographic analysis indicated that annexin VI was expressed on the cell surface in slightly higher amounts on highly metastatic RAW117 cells, and it was not removable by EDTA treatment. Anti-annexin VI antibodies inhibited the adhesion of RAW117 cells to fixed or unfixed murine hepatic sinusoidal endothelial cells by approximately 40%, indicating a role for annexin VI in mediating a portion of the Ca(2+)-dependent RAW117 cell adhesion to target liver microvessel endothelial cells. PMID- 7982480 TI - A genetic approach to elucidating eukaryotic iron metabolism. AB - Studies of mutants of the yeast Saccharomyces cerevisiae have led to the identification of genes required for high affinity iron uptake. Reduction of iron (III) outside the cell is accomplished by means of reductases encoded by FRE1 and FRE2, homologues of the gp91-phox component of the oxygen reductase of human granulocytes. High affinity iron (II) transport from the exterior to the interior of the cell occurs by means of a transport system that has not been molecularly characterized. However, the transport process requires the activity of a copper containing oxidase encoded by FET3. The amino acid sequence of this protein resembles other multi-copper oxidases, including mammalian ceruloplasmin. High affinity copper uptake mediated by the copper transport protein encoded by CTR1 is required to provide the FET3 protein with copper, and thus copper uptake is indirectly required for ferrous iron uptake. These genetic elements of yeast and their relationships may be conserved in complex eukaryotic organisms. PMID- 7982481 TI - Inhibition of the respiratory burst in mouse macrophages by ultra-low doses of an opioid peptide is consistent with a possible adaptation mechanism. AB - The respiratory burst induced by phorbol myristate acetate in mouse macrophages was inhibited by ultra-low doses (10(-15)-10(-13) M) of an opioid peptide [D Ala2]methionine enkephalinamide. The effect disappeared at concentrations above and below this range. The inhibition approached 50% and was statistically significant (P < 0.001). Increasing the time of the opioid incubation with cells brought about a shift in the maximal effect to lower concentrations of the opioid (from 10(-13) to 5 x 10(-15) M) and led to a decrease in the value of the effect, fully in accord with the previously proposed adaptation mechanism of the action of ultra-low doses. PMID- 7982482 TI - Somatostatin receptor subtype SSTR2 mediates the inhibition of high-voltage activated calcium channels by somatostatin and its analogue SMS 201-995. AB - Somatostatin and its analogue SMS 201-995 inhibit high voltage-activated (HVA) Ca2+ currents in the rat insulinoma cell line RINm5F which stably express cloned human somatostatin receptor subtype 2 (hSSTR2). In contrast, neither somatostatin nor SMS 201-995 suppresses the HVA Ca2+ currents in RINm5F which stably express cloned hSSTR1. These results suggest that somatostatin-induced inhibition of HVA Ca2+ currents is mediated by a specific receptor subtype and that inhibition of calcium influx through HVA Ca2+ channels is one of the mechanisms of SMS 201-995 action on inhibitory processes of hormone secretion and cell proliferation. PMID- 7982483 TI - Chemical crosslinking studies of extrinsic proteins in cyanobacterial photosystem II. AB - Chemical crosslinking with a zero-length crosslinker, 1-ethyl-3-(3 dimethylaminopropyl) carbodimide hydrochloride, was applied to a cyanobacterial photosystem II complex retaining three extrinsic proteins, the 33 kDa manganese stabilizing protein, cytochrome (cyt) c-550 and the 12 kDa protein. Three major crosslinked products were obtained in addition to the crosslinked product between the extrinsic 33 kDa and the intrinsic CP47 proteins. They were identified to be: cyt c-550-12 kDa; cyt c-550-12 kDa-33 kDa; D2-cyt c-550-12 kDa. These results indicate that the three extrinsic proteins are closely located with each other in cyanobacterial PSII, supporting the previous proposal that, like the 33 kDa protein; cyt c-550 and the 12 kDa protein are associated with PSII at the lumenal side of thylakoids. The results also suggested that the D2 reaction center protein provides a direct binding site for the extrinsic cyt c-550. PMID- 7982484 TI - Localization of hormone-sensitive lipase to rat Sertoli cells and its expression in developing and degenerating testes. AB - Using in situ hybridization, hormone-sensitive lipase was found to be expressed in a stage-dependent manner in Sertoli cells of rat testis. No expression was found in Leydig cells but expression in spermatids could not be excluded. These results suggest a role for hormone-sensitive lipase in the metabolism of lipid droplets in Sertoli cells, in contrast to its previously proposed function in steroid biosynthesis. The expression of testicular hormone-sensitive lipase mRNA and protein, both larger in size compared to other tissues, coincided with the onset of spermatogenesis and was dependent on scrotal localization of the testis, suggesting a temperature-dependent, pretranslational regulation of expression. PMID- 7982485 TI - Synaptobrevin cleavage by the tetanus toxin light chain is linked to the inhibition of exocytosis in chromaffin cells. AB - Exocytosis of secretory granules by adrenal chromaffin cells is blocked by the tetanus toxin light chain in a zinc specific manner. Here we show that cellular synaptobrevin is almost completely degraded by the tetanus toxin light chain within 15 min. We used highly purified adrenal secretory granules to show that synaptobrevin, which can be cleaved by the tetanus toxin light chain, is localized in the vesicular membrane. Proteolysis of synaptobrevin in cells and in secretory granules is reversibly inhibited by the zinc chelating agent dipicolinic acid. Moreover, cleavage of synaptobrevin present in secretory granules by the tetanus toxin light chain is blocked by the zinc peptidase inhibitor captopril and by synaptobrevin derived peptides. Our data indicate that the tetanus toxin light chain acts as a zinc dependent protease that cleaves synaptobrevin of secretory granules, an essential component of the exocytosis machinery in adrenal chromaffin cells. PMID- 7982486 TI - Molecular cloning and characterisation of a putative pectin methylesterase cDNA in Arabidopsis thaliana (L.). AB - Pectin methylesterase (PME) is a cell wall enzyme that catalyses the de esterification of pectins leading to fundamental changes which confer new properties to the micro-environment of each cell. In order to elucidate the meaning of PME-mediated changes of pectin in the time course of cell differentiation, we attempted to study the regulation of PME genes in Arabidopsis thaliana. In this report, the first full cDNA sequence showing sequence similarities with other PME genes characterised so far in other plant species has been isolated from an Arabidopsis shoot cDNA library. This ATPMEl cDNA is 1,970 bp long and contains an open reading frame encoding a protein of 64.1 kDa and a basic pI of 8.7 as predicted from the nucleotide sequence. Northern blot analyses denoted changes in the expression level of the ATPMEl mRNA according to plant organs. High mRNA levels were found in young developing organs such as cauline leaves while they were significantly lower in rosette leaves, stems and inflorescences, and almost undetectable in roots. Beside this molecular approach, isoelectrofocusing analyses revealed the occurrence of three PME isoforms in Arabidopsis. Two PME isoforms with pI values of 4.9 and 9.1 were found throughout the plant, but at a higher level in the root, while an other PME isoform with a pI of 5.7 was essentially detected in the inflorescence. The relationship between our observations and the data reported for other plant species is discussed. PMID- 7982487 TI - Does the solid-state structure of endothelin-1 provide insights concerning the solution-state conformational equilibrium? AB - Additional NMR data (local NOE ratios and chemical shifts) for endothelin-1 supporting the existence of a relatively regular helix initiated abruptly at Lys9 (with Asp8 as an N-cap) and extending in all cases to Cys15 (and in a frayed form to Asp18 in some analogs) is presented. The recent solids-state structure [Janes et al. (1994), Nature Struct. Biol. 1, 311-319], in contrast, places the helix in the extreme C-terminal section of structure and the Lys9-Tyr13 segment is not helical. The X-ray structure does not predict the NOEs or chemical shifts observed for endothelins in aqueous media containing polar organic co-solvents. An analysis of the chemical shift data for reporter groups indicates that the helical conformational preference of endothelins is not significantly altered by the addition of acetonitrile, acetic acid, or ethylene glycol. The validity of the analytic strategy is supported by results for both more rigid and less helical analogs. We conclude that the structure observed in crystals obtained from purely aqueous media is influenced by intermolecular interactions in the solid state and is not a significant contributor to the conformational equilibrium observed for monomeric ET-1. PMID- 7982488 TI - Glycotripeptides are released by yeast but not by mammalian microsomes. AB - Glycotripeptides generated in vivo in the endoplasmic reticulum (ER) have been used as markers to assess the rate of vesicular bulk flow from the ER via the Golgi apparatus to the plasma membrane in mammalian cells. The applicability of such glycotripeptides as markers for bulk flow along this pathway has been questioned by a report on non-vesicular release of glycotripeptides from yeast semi-intact spheroplasts. We have therefore investigated direct release of glycotripeptides from yeast and from mammalian microsomes and report here that such release is specific to the yeast system and cannot be detected in mammalian microsomes. PMID- 7982489 TI - Interaction between the zinc (II) and the heparin binding site of the Alzheimer's disease beta A4 amyloid precursor protein (APP). AB - The Alzheimer's disease beta A4 amyloid precursor protein (APP) has been suggested to be involved in regulation of cell growth, neurite outgrowth and adhesiveness through binding to heparin sulfate proteoglycans. In order to unravel the molecular mechanisms underlying those functions in vitro we show that APP binds in a time dependent and saturable manner to the glycosaminoglycan side chains of proteoglycans but not to chondroitinsulfate. We also demonstrate an interaction between the high affinity heparin binding site within the carbohydrate domain of APP and the zinc(II) binding site of APP. We show that the affinity for heparin is increased two- to four-fold in the presence of micromolar zinc(II). Thus micromolar concentrations of zinc(II) appear to be able to modulate the binding of APP to heparin side-chains of proteoglycans and as shown previously [Science 265 (1994) 1464-1467] to induce the aggregation of soluble amyloid beta A4 protein. PMID- 7982490 TI - Identification of the axial heme ligands of cytochrome b556 in succinate: ubiquinone oxidoreductase from Escherichia coli. AB - Electron paramagnetic resonance (EPR) and near-infrared magnetic circular dichroism (MCD) have been used to identify the ligands to the cytochrome b556 component of succinate: ubiquinone oxidoreductase (succinate dehydrogenase) from Escherichia coli. The 'highly axial low spin' (HALS) EPR spectrum suggests bis(histidine) ligation of the heme with the histidines in a staggered configuration. The near-infrared MCD spectrum exhibits a low energy maximum at 1600 nm which is also clearly indicative of bis(histidine) ligation of the heme iron. The data unambiguously demonstrate that the heme b556 is ligated to E. coli succinate dehydrogenase via two histidines. PMID- 7982491 TI - Okadaic acid stimulates ouabain-sensitive 86Rb(+)-uptake and phosphorylation of the Na+/K(+)-ATPase alpha-subunit in rat hepatocytes. AB - Ca(2+)-mobilizing and cAMP-dependent hormones rapidly increase sodium, potassium dependent adenosine triphosphatase (Na+/K(+)-ATPase)-mediated transport in rat hepatocytes. To explore the possible role of protein phosphatases in these responses we used a protein phosphatase inhibitor, okadaic acid. Okadaic acid stimulation of ouabain-sensitive 86Rb(+)-uptake was maximal between two and three minutes and displayed an EC50 of 41 +/- 1 nM. Inhibition of Na+/H+ exchange with an amiloride analog abolished the response to insulin, but had no effect on okadaic acid-mediated stimulation of Na+/K(+)-ATPase transport. In hepatocytes metabolically-radiolabeled with 32Pi, okadaic acid stimulated the incorporation of radioactivity into several 95 kDa peptides, one of which reacted with anti LEAVE peptide antisera, that recognizes Na+/K(+)-ATPase alpha-subunits. In other experiments Na+/K(+)-ATPase was immunoprecipitated from detergent-solubilized membrane fractions of metabolically-radiolabeled cells with an antisera to purified rat kidney Na+/K(+)-ATPase. A 95 kDa phosphoprotein was immunoprecipitated using anti-Na+/K(+)-ATPase antisera, but not by preimmune serum. Okadaic acid stimulated incorporation of radioactivity into this band by 220 +/- 28%. These findings provide support for the hypothesis that rapid stimulation of hepatic Na+/K(+)-ATPase by hormones may be related to protein kinase/phosphatase-mediated changes in the phosphorylation state of the Na+/K(+) ATPase alpha-subunit. PMID- 7982492 TI - Effects of transient expression of spermidine/spermine N1-acetyltransferase in COS cells. AB - Mammalian spermidine/spermine N1-acetyltransferase (SSAT) was transiently expressed in COS cells. As compared to COS cells transfected with control vector alone, cells transfected with the expression vector containing SSAT cDNA contained lower concentrations of spermidine and spermine. The putrescine content, on the other hand, was markedly increased in the COS cells expressing large amounts of SSAT. These changes in polyamine content were most likely caused by an interconversion of spermine and spermidine into putrescine. The SSAT induced changes in cellular polyamine content resulted in a compensatory increase in the activities of ornithine decarboxylase and S-adenosylmethionine decarboxylase, i.e. the enzymes catalyzing the rate-limiting steps in polyamine biosynthesis. This is the first demonstration that a primary increase in SSAT activity will induce an interconversion-like change in the polyamine levels and the physiological role of SSAT is most likely to protect cells against too high concentrations of spermidine and spermine. PMID- 7982493 TI - Receptor availability defines the extent of agonist-mediated G-protein down regulation in neuroblastoma x glioma hybrid cells transfected to express the beta 2-adrenoceptor. AB - Sustained exposure of neuroblastoma x glioma hybrid, NG108-15, cells transfected to express the human beta 2-adrenoceptor (clone beta N22) to isoprenaline or iloprost (an agonist at the endogenously expressed IP prostanoid receptor) resulted in a substantial and selective down-regulation of the alpha subunit of the G-protein Gs. Treatment of these cells with the irreversible beta adrenoceptor antagonist bromoacetyl alprenolol menthane diminished both the potency and the maximal ability of isoprenaline but not of iloprost to cause Gs alpha down-regulation. These results demonstrate that the extent of agonist mediated Gs alpha down-regulation is dependent upon the availability of receptor to agonist. PMID- 7982494 TI - Roles of Arg231 and Tyr284 of Thermus thermophilus isocitrate dehydrogenase in the coenzyme specificity. AB - The coenzyme binding site of isocitrate dehydrogenase from Thermus thermophilus was analyzed by site-directed mutagenesis. The mutation analysis revealed that Arg231 and Tyr284 are involved in the discrimination between NAD and NADP, suggesting that these two residues interact with 2'-phosphate group of NADP. PMID- 7982495 TI - Tamoxifen stimulates phospholipase D activity by an estrogen receptor-independent mechanism. AB - The effects of tamoxifen (TAM), a widely used agent in the treatment of breast cancer, were examined on phospholipase D (PLD)-mediated phospholipid hydrolysis. In drug-sensitive MCF-7 human breast carcinoma cells TAM, similar to several well established activators of PLD, had no effect on phospholipid hydrolysis. In an estrogen receptor-deficient multidrug-resistant subline of MCF-7 cells, TAM preferentially stimulated the hydrolysis of phosphatidylethanolamine; two-fold stimulation required 2.5 or 5 microM TAM in the absence or presence of serum, respectively. In NIH 3T3 fibroblasts significant (4- to 4.8-fold) stimulation of phosphatidylethanolamine and phosphatidylcholine hydrolysis in the presence of serum required 10 microM TAM. These data establish that TAM can stimulate PLD activity by an estrogen receptor-independent mechanism. PMID- 7982496 TI - The functional expression of p47-phox and p67-phox may contribute to the generation of superoxide by an NADPH oxidase-like system in human fibroblasts. AB - Recent evidence suggests that a number of non-phagocytic cell types may contain a superoxide generating NADPH oxidase. Studies to data on cultured human fibroblasts have primarily concerned the identification of cytochrome b558, whilst expression of other NADPH oxidase components have not been addressed. In this study we have investigated the expression of NADPH oxidase with particular reference to the cytosolic factors p47-phox and p67-phox. Reverse transcriptase polymerase chain reaction (RT-PCR) showed that human fibroblasts express mRNA for p47-phox, p67-phox and p22-phox. Expression of the gp91-phox transcript was not detected, indicating that human fibroblasts may possess an NADPH oxidase isoenzyme. Western blot analysis of human fibroblast cytosol, using an anti-p47 phox antibody (JW-1), identified a 47 kDa protein. Cell-free reconstitution assays showed that fibroblast cytosol could initiate superoxide generation when mixed with either human fibroblast membranes (0.16 nmol superoxide/min/microgram membrane protein), or resting human neutrophil membranes (0.20 nmol superoxide/min/microgram membrane protein). These data indicate that the expression of p47-phox and p67-phox by human fibroblasts may contribute to the cells' generation of superoxide. PMID- 7982497 TI - Mycotin: a lectin involved in the adherence of Mycobacteria to macrophages. AB - Pathogenic Mycobacteria colonize host macrophages. Attachment of these organisms to macrophages is the preliminary step prior to invasion of the macrophages by the bacteria. Western blot confirmed that walls of Mycobacterium avium and Mycobacterium tuberculosis contain molecules which are immunologically related to mycotin, a lectin found in Mycobacterium smegmatis. We have demonstrated that the adherence of Mycobacteria to macrophages is significantly inhibited by anti mycotin antibody or the mycotin-specific sugar, mannan. These observations suggest that prevention of the interaction of mycotin-related molecules on the surfaces of Mycobacteria with mannose-specific receptors on macrophages, offers an important approach for blocking attachment of pathogenic Mycobacteria to macrophages, thereby preventing infection. PMID- 7982498 TI - The antiprogestatin drug RU 486 potentiates doxorubicin cytotoxicity in multidrug resistant cells through inhibition of P-glycoprotein function. AB - The antiprogestatin drug RU 486 was examined for its effect on doxorubicin cellular retention and cytotoxicity in multidrug resistant cells overexpressing P glycoprotein (P-gp). RU 486 was shown to strongly enhance intracellular accumulation of doxorubicin in both rat hepatoma RHC1 and human leukemia K562 R7 drug-resistant cells but had no action in SDVI drug-sensitive liver cells. The antiprogestatin drug when used at 10 microM, a concentration close to plasma concentrations achievable in humans, was able to hugely increase the sensitivity of RHC1 cells to doxorubicin. RU 486 appeared to prevent the P-gp-mediated doxorubicin efflux out of RHC1 cells and was demonstrated to interfere directly with P-gp drug binding sites since it blocked P-gp labelling by the photoactivable P-gp ligand azidopine. These results thus demonstrate that RU 486 can downmodulate anticancer drug resistance through inhibition of P-gp function. PMID- 7982499 TI - Enzyme-catalyzed uridine phosphorolysis: SN2 mechanism with phosphate activation by desolvation. AB - The rate of uridine phosphorolysis catalyzed by uridine phosphorylase from Escherichia coli decreases with increasing ionic strength. In contrast, the rate was increased about twofold after preincubation of uridine phosphorylase with 60% acetonitrile. These data correlate with known effects of polar and bipolar aprotic solvents on SN2 nucleophilic substitution reactions. The enzyme modified with fluorescein-5'-isothiocyanate (fluorescein residue occupies an uridine binding subsite [Komissarov et al., (1994) Biochim. Biophys. Acta 1205, 54-58]) was selectively modified with irreversible inhibitor SA-423, which reacts near the phosphate-binding subsite. The double-modified uridine phosphorylase is assumed to imitate the enzyme-substrate complex. Modification with SA-423 was accompanied with dramatic changes in the absorption spectrum of active site linked fluorescein, which were identical to those for fluorescein in a hydrophobic medium, namely 80% acetonitrile. The data obtained suggest that an increase in active site hydrophobicity leads to phosphate desolvation and facilitates the enzymatic SN2 uridine phosphorolysis reaction. PMID- 7982500 TI - Distinct cadherin-catenin complexes in Ca(2+)-dependent cell-cell adhesion. AB - Catenins are peripheral cytoplasmic proteins originally identified in association with the mouse epithelial cell adhesion molecule E-cadherin. Molecular cloning and primary structure analysis demonstrated that alpha-catenin is homologous to vinculin and the beta-catenin is homologous to human plakoglobin and the Drosophila gene product armadillo. With the use of peptide-specific anti plakoglobin antibodies were confirm here that plakoglobin is a component of the cadherin-catenin complex and that it is most likely identical to gamma-catenin. We show that plakoglobin binds directly to E-cadherin. We consolidate the biochemical evidence for the existence of two distinct and separable E-cadherin catenin complexes in the same cell. One complex is composed of E-cadherin, alpha- and beta-catenin, the other of E-cadherin, alpha-catenin and plakoglobin. A similar distinct association with catenins is also found for other cadherins. Comparison of different cell lines revealed that the relative amounts of the two complexes vary depending on cell types. PMID- 7982501 TI - Germinating conidiospores of Aspergillus amino acid auxotrophs are hypersensitive to heat shock, oxidative stress and DNA damage. AB - Germinating conidiospores (conidia) of Aspergillus nidulans amino acid-requiring strains are hypersensitive to heat, oxidative stress, UV radiation and chemical mutagens when compared with other strains. They also showed an increased mutation rate. Sensitivity to stress conditions has been correlated with an abnormal RAS/cAMP pathway in mutants of S. cerevisiae. We suggest that the RAS/cAMP pathway is defective in germinating conidia of Aspergillus amino acid auxotrophs and that this is responsible for suppressing DNA repair and conferring sensitivity to oxidative stress and heat shock. PMID- 7982502 TI - Differential effects of guanine nucleotides on kainic acid binding and on adenylate cyclase activity in chick optic tectum. AB - In G protein-coupled receptors, neurotransmitter-induced binding of GTP to G proteins triggers the activation of effector systems while simultaneously decreasing the affinity of the transmitter for its specific binding site within the receptor-G protein complex. In the present study we show that, in the chick optic tectum, guanine nucleotides inhibit the binding of the glutamate analog, kainate, and activate adenylate cyclase by different mechanisms and acting on different sites. GMP-PNP, a non-hydrolyzable analog of GTP, binds tightly to G proteins so that the binding is stable even after exhaustive washing. By use of this property, we have prepared membrane samples in which G protein GTP-binding sites are pre-saturated with GMP-PNP. Experiments carried out with these membranes show that GMP-PNP, GDP-S and GMP inhibit the binding of [3H]kainate by interacting with site(s) unrelated to G proteins, whereas GMP-PNP activates adenylate cyclase activity by binding to G proteins. PMID- 7982503 TI - Effect of Paramecium biaurelia cytoplasm transplantation on the duration of the interautogamous interval (IAI) in Paramecium tetraurelia. AB - The cytoplasm of Paramecium biaurelia in various stages of IAI was transplanted to Paramecium tetraurelia cells of the same clonal age. Such donor cytoplasm was effective in retardation of the expression of autogamy in the recipient clones. The results suggest that the cytoplasm of Paramecium biaurelia may contain the autogamous immaturity factor whose level changes during the run of IAI and whose specificity is the same as in Paramecium tetraurelia. PMID- 7982504 TI - Paramecium triaurelia and other species of the aurelia complex in the Kaczawskie Mts and Plateau (western Sudeten). AB - The present investigations revealed the occurrence of Paramecium triaurelia on the territory of the Kaczawskie Plateau, while its presence was confirmed in the Kaczawskie Mts. In Poland, the presence of this species was recorded only in the Western Sudeten, in spite of many years of investigation. As the result of the studies also the occurrence of P. biaurelia and P. novaurelia was recorded on the territory of the Kaczawskie Mts and the Kaczawskie Plateau. PMID- 7982505 TI - Contemporary investigations on the Paramecium aurelia species complex in the Tatras. Preliminary report. PMID- 7982506 TI - Effects of atmospheric pollution on Paramecium sp. cells. AB - The toxicity level of heterocyclic compound fractions obtained from dust in Silesia for Paramecium primaurelia was studied. For the estimation of their toxicity a special scale elaborated for this material was used. It was found that the level of toxicity of investigated fractions differed, depending on the sampling place and season of the year. PMID- 7982507 TI - On the distribution of catecholamines in Promesostoma balticum (Turbellaria, Neorhabdocoela, Promesostomatidae). AB - The distribution of putative catecholamines has been previously studied in the nervous system of three Promesostoma species using the glyoxylic-acid-induced fluorescence (GAIF) method. In this communication, the results are reported of a similar study of Promesostoma balticum, which is classified to another group of species in the genus. Promesostoma species from two different species groups differed in the position of neurons associated with the ventral and lateral cords. All the studied species of Promesostoma demonstrated doubled dorsal neurons in so called anterior complex (AnDo), a character which differentiates this genus from the other studied Typhloplanoida. PMID- 7982508 TI - Preferential accumulation of putative "dics" under non-selective conditions during in vivo progression of a murine ascites sarcoma. AB - The occurrence and accumulation of dicentric marker (dic) chromosomes with terminal centromeres have been documented in a murine ascites sarcoma cell line (S180) during in vivo progression of the tumour for many years. Initially, in 1975, the cell line had only one such "dic" but currently the predominant clone is represented by three such "dics". Moreover, the emergence of a new sub-clone with four dicentric markers has recently been recorded. The possible significance of the preferential accumulation of "dics" in the cell line is discussed. PMID- 7982509 TI - Cytoplasmic regulation of the interautogamous interval (IAI) in Paramecium tetraurelia. AB - Cytoplasm from individuals at different stages of the interautogamous interval (IAI) transferred into cells at constant clonal age (during the second half of the IAI) caused statistically significant changes in the IAI in clones initiated from recipients. Cytoplasm from the cells in the first half of the IAI caused prolongation of this period, cytoplasm from slightly older cells had no effect, while that derived from cells being a few fissions before the next autogamy shortened the duration of the IAI. This suggests that the cytoplasm of P. tetraurelia contains an autogamous immaturity factor retarding the occurrence of autogamy, and that at the end of the IAI there appears a component accelerating this process. PMID- 7982510 TI - How to compare and report department specific mortality rates for peer review using the Perinatal Database of The Netherlands. AB - Since characteristics of patient populations of obstetric departments vary substantially with respect to the pathology presented, (perinatal) mortality rates as such can not be used for a fair peer review without adjustment for those differences. Using the Perinatal Database of The Netherlands (LVR), data on approximately 80,000 newborns annually from 1985 to 1991 inclusive were used in statistical models to predict the perinatal mortality risks of four subpopulations of different gestational age in about 125 obstetric departments. As predictors for perinatal mortality we used only those risk factors which were judged to reflect the 'pathology' of the patient; risk factors associated with or resulting from hospital care and/or policy are (by definition) excluded. The statistical technique of logistic regression was used. The expected and observed mortality within each of these four subpopulations (for 1985-1991) was sent anonymously to each department as a specially designed graphical overview. This method of (anonymous) peer review was met favourably. In peer review the difference between observed and expected mortality should be used, rather than mortality per se, to adjust for differences in basic risk in the intake populations on which the departmental policy has no influence. PMID- 7982511 TI - Antenatal fetal demise in multiple gestation--the outcome of surviving fetus at one to four years of age. AB - The outcome of 26 multifetal pregnancies with single fetal demise after 12 weeks of pregnancy cared for at the University Medical School of Zagreb from 1986 to 1991 is presented. Growth retardation of dead and surviving infant and pathohistological findings consistent with reduced uterine blood flow to cotyledonary space was the most frequent complication, irrespective of the type of placentation. Perinatal infection was the most frequent neonatal complication. Neonatal asphyxia was observed in only one infant. The outcome at 1-4 years of age was perfect in 14 out of 15 surviving infants for whom data are available. An early diagnosis of multifetal pregnancy, based essentially on ultrasonography and appropriate monitoring of the mother and the survivor, with cesarean delivery carried out at first signs of imminent asphyxia, is the best guarantee for a favorable outcome. PMID- 7982512 TI - Sensitivity of intrapartum group B streptococcal screening and in vitro comparison of four rapid antigen tests. AB - OBJECTIVES: To evaluate the sensitivity of intrapartum screening for group B streptococcal (GBS) colonization and to compare 4 rapid GBS antigen tests in vitro. DESIGN: Two swabs of the lower vagina of 769 parturients were taken; one swab was cultured, the other was frozen at -70 degrees C until antigen testing with the Group B Strep Test (Quidel) of the culture positive samples was performed. The Quidel test was then compared with 3 other rapid GBS antigen tests in vitro: Wellcogen Strep B (Wellcome Diagnostics), Slidex meningite Strepto B (bioMerieux) and ICON Strep B (Hybritech). The supernatant of 29 GBS cultures in Todd-Hewitt broth was tested in bacterial concentrations of 10(6), 10(7), and 10(8) Colony-forming Units (CFU)/ml, respectively. RESULTS: Lower vagina GBS carrier rate was 13.4% (103/769) and heavy colonization (growth density 3 and 4 on blood agar plates) was found in 5.2% (40/769). The Group B Strep Test detected 11% (11/103) of GBS carriers, with a sensitivity for heavy colonization of 25% (10/40). In vitro none of the tests scored positively with a concentration of 10(6) CFU/ml, while with 10(7) CFU/ml the enzyme immunoassay tests (Quidel, Hybritech) were more sensitive (McNemar test, P < 0.05) than the latex agglutination tests (Wellcome Diagnostics, bioMerieux). CONCLUSIONS: Although in vitro the enzyme immunoassay tests are more sensitive than the latex agglutination tests, sensitivity in vivo is too low to recommend the use of rapid antigen tests for general screening. PMID- 7982513 TI - Glucagon stimulation test: assessment of beta-cell function in gestational diabetes mellitus. AB - OBJECTIVE: Because women with gestational diabetes mellitus have a risk of up to 60% for the later development of type II diabetes, we used the intravenous glucagon stimulation test to evaluate beta-cell function in pregnant women. PATIENTS: Twenty-seven pregnant women with one or more risk factors for gestational diabetes had an intravenous beta-cell stimulation test. Glucose, C peptide and insulin levels were measured at baseline and 5, 10 and 15 min after the administration of 1 mg glucagon. The women were classified using the 75-g oral glucose tolerance test according to World Health Organization criteria. During the oral glucose tolerance test glucose, C-peptide and insulin levels were measured at baseline and at 2 h. RESULTS: Insulin and C-peptide responses were significantly lower in pregnant women with impaired glucose tolerance and diabetes compared with women with normal glucose tolerance. CONCLUSION: This study shows gradually decreasing insulin secretion from normal to subnormal in pregnant women without and with glucose intolerance, and diabetes mellitus, respectively. PMID- 7982514 TI - Routine clinical policy and application of Doppler measurements in suspected intrauterine growth retardation in university hospitals in The Netherlands. AB - Suspected intrauterine growth retardation is a clinical problem with financial consequences, as it can lead to costly, in-hospital fetal monitoring. At present, no prospective 'gold standard' for growth retardation exists. Hence, a proportion of the fetuses suspected are likely to be genetically small, in which case hospitalization is superfluous. Doppler ultrasound measurements might be applied to differentiate between growth retardation and genetically based smallness. Before the diagnostic effectiveness of Doppler ultrasound can be evaluated, however, the magnitude of the problem of suspected intrauterine growth retardation, or what it is experienced to be, must be known. The occurrence of suspected intrauterine growth retardation, routine clinical policy, and use of Doppler ultrasound techniques were assessed by a questionnaire among obstetricians in the university hospitals in The Netherlands. Of the obstetricians approached, 81% responded (59/73). Intrauterine growth retardation was defined mainly by a lag in fundal height of at least 3 weeks. It is suspected in about 11% of singleton pregnancies. An estimated 70% of those suspected of growth retardation are hospitalised. Fewer than half of the respondents thought Doppler ultrasound measurements an asset to antenatal diagnosis. Five of the eight university hospital clinics used Doppler measurements in clinical decision making. Sixty percent of responding obstetricians were of the opinion that there was a 'routine clinical policy' in suspected intrauterine growth retardation. PMID- 7982515 TI - Maternal mortality in Europe. AB - Maternal mortality rates (or ratios) are widely used as one indicator of the quality of medical care. There has been concern that conclusions may be drawn from unreliable data. A survey of practices in European countries confirms that there are differences in interpretation of definitions and evidence of significant under-reporting in official returns of vital statistics. Actual and potential sources of error are identified and a need for greater precision and uniformity of data collection is established. PMID- 7982516 TI - Concomitant measurements of interleukin-6 (IL-6) in serum and peritoneal fluid of patients with benign and malignant ovarian tumors. AB - The multifunctional cytokine interleukin-6 (IL-6) is produced by epithelial and mononuclear cells as well as by ovarian carcinoma cells. A prospective study was initiated to evaluate the clinical significance of systemic and local measurements of IL-6 concentrations in 67 patients with ovarian tumors. Eighteen patients who underwent laparotomy for ovarian carcinoma showed elevated levels of IL-6 in the serum as well as in the peritoneal cavity in comparison to patients with benign ovarian tumors. Furthermore, patients with advanced ovarian cancer, according to Figo-Stages III/IV, demonstrated higher IL-6 levels in the serum and ascites, respectively, than patients with Figo-Stages I/II reflecting low tumor burden. The results of the study suggest that IL-6 plays a key role in tumor-host interaction, particularly, in the possible facilitated spread of ovarian cancer cells. PMID- 7982517 TI - Management of postmenopausal osteoporosis. AB - More than 25% of postmenopausal women are at risk of osteoporosis. In order to avoid its consequences, it is necessary to find an appropriate prevention and/or treatment. We studied: (1) 15 postmenopausal women treated with percutaneous estradiol (50 micrograms/24 h) plus MPA (10 mg/10 days/month); (2) 15 postmenopausal women treated with synthetic calcitonin nasal spray at the daily dose of 100 IU; (3) 10 postmenopausal women treated with nandrolone decanoate (50 mg every 3 weeks); (4) 10 postmenopausal women treated with ipriflavone (600 mg/day); and (5) 10 postmenopausal women treated with sodium fluoride (20 mg) plus calcium (600 mg). Clinical examination, bone mass measurement (total BMD), hematochemical and urinary parameters of bone metabolism (calcium, urinary hydroxyproline, PTH) and growth factors (as IGF-I and TNF-beta) were evaluated. After 6 months of therapy, a complete prevention of bone resorption was achieved. In agreement with current literature, we observed that the various therapeutic approaches have all some positive effect on BMD, with different results on pain, blood biochemical parameters and growth factors' concentrations. PMID- 7982518 TI - Some mechanical properties of skinned fibres of pregnant human myometrium. AB - The properties of contractile elements and intracellular Ca2+ storage sites of pregnant human myometrium were studied by recording the mechanical responses in skinned (saponin-treated and membrane-permeable) fibres. Calmodulin increased the amplitude of contractions induced by Ca2+ and the Ca2+ sensitivity for contractile elements in small myometrium strips, but PGF2 alpha, PGE2, oxytocin, or cyclic AMP failed to produce similar effects. After accumulation of Ca2+ in intracellular Ca2+ storage sites, 10 mumol/l PGF2 alpha, 10 mumol/l PGE2, 30 mmol/l caffeine, and 20 mumol/l InsP3 (inositol-trisphosphate) produced contractions by releasing Ca2+ from storage sites. However, 20 nmol/l oxytocin had no effects under the same conditions. The InsP3 sensitive Ca2+ store was much larger than those of PGs or caffeine. These results suggest that pregnant human myometrium contracts with low Ca2+ by a calmodulin sensitive system. The data also indicate that direct application of PGF2 alpha, or PGE2 into the cells discharges Ca2+ from Ca2+ storage sites and that oxytocin extricates Ca2+ via a pathway involving InsP3 by activation of phosphoinositide turnover. We suggest that these agents induce added contractile responses due to a Ca2+ release mechanism from store sites in addition to the influx of Ca2+ from the extracellular space. PMID- 7982519 TI - Conversion of atrial fibrillation with ajmaline in a pregnant woman with Wolff Parkinson-White syndrome. AB - Pregnancy is related to an increased frequency of arrhythmias in asymptomatic patients with Wolff-Parkinson-White syndrome, which might lead to sudden death. A 40-year-old woman, with Wolff-Parkinson-White syndrome which was not diagnosed until pregnancy, presented in the 34th week with an atrial fibrillation, with high risk criteria for ventricular fibrillation. Intravenous ajmaline was given to convert the tachyarrhythmia to sinus rhythm. We obtained an excellent maternal control with no maternal or fetal adverse effects. PMID- 7982520 TI - Varicella zoster virus infection during pregnancy: the limits of prenatal diagnosis. AB - In a mother with clinical evidence of chicken-pox at 12.5 weeks, fetal herpes varicella zoster infection was revealed by transient fetal ascites with liver calcifications at 27 weeks routine ultrasound. At 27 and 35 weeks fetal blood sampling and amniocentesis failed to demonstrate fetal viral infection. However, the diagnosis was confirmed postnatally based on thoracic herpes zoster at 8 months in an otherwise healthy infant. Polymerase chain reaction (PCR) on stored amniotic cells performed retrospectively was positive for varicella zoster virus (HVZV). This observation suggests that (1) in contrast to PCR, conventional fetal biology lacks sensitivity for prenatal diagnosis of HVZV infection, (2) the association of fetal sonographic abnormalities and positive amniotic PCR can be associated with a favorable pediatric outcome. Therefore, prenatal diagnosis of HVZV infection should be considered with the greatest caution. PMID- 7982521 TI - Herniation of the omentum after laparoscopy. AB - The use of laparoscopic surgery is increasing. With this new type of surgery new complications will occur. One of these complications is herniation via the troicart incision as a result of the use of large troicarts. This problem could be solved by using the Z-incision technique or by suturing the fascia. Two cases of herniation of the omentum are described and discussed. PMID- 7982522 TI - Amount of antenatal care and infant outcome. AB - The connection between the amount of antenatal care and pregnancy outcome was studied using the 1987 Finnish Medical Birth Registry. A total of 57,108 women were included in the analysis. The timing of initiation of antenatal care and the relative number of antenatal visits (adjusted by gestation length), were used as measures of amount of antenatal care. Nine outcome variables measuring infant health and interventions were studied. Logistic regression was used to adjust for differences in maternal background characteristics. Women beginning antenatal care after the 16th week of gestation had the poorest outcome. Early attending multiparous women had a higher risk of low birthweight, premature infants, caesarean section and instrumental delivery than did those with average timing of their first attendance. For primigravidas, the increased risk was of prematurity only. A U-shaped curve was found for most of the outcome variables in regard to relative number of visits. The women with many visits had the poorest outcome, and also the highest rates of caesarean section and induction of labour. One reason for the unexpectedly high risks for early attenders may be connected with the content of antenatal care. In Finland, it might be possible to reduce the total number of antenatal visits without having any negative effect on infant health. PMID- 7982523 TI - Respiratory allergy: hazard identification and risk assessment. AB - Various chemicals and proteins of industrial importance are known to cause respiratory allergy, with occupational asthma being the most important manifestation of the disease. This paper describes clinical syndromes, mechanisms associated with occupational respiratory hypersensitivity, and methods available currently for the prospective identification of potential respiratory allergens. Certain classes of chemicals are commonly associated with occupational respiratory allergy. There is insufficient information, however, to predict respiratory sensitization potential from analysis of structure alone, although reactivity with proteins is likely to be relevant. As yet there exist no fully validated or widely applied predictive methods or internationally harmonized guidelines. The most promising predictive animal methods are the mouse IgE test and guinea pig models. Work in mice has focused upon events occurring during the induction phase of sensitization following primary encounter with the test chemical. In contrast, guinea pig models have been used primarily to identify respiratory allergens (chemicals or proteins) as a function of elicitation reactions induced in previously sensitized animals. Given the possible serious health manifestations of respiratory allergy, early identification of respiratory sensitizers is urgently required. The two methods should, as a priority, be developed further and the production of a detailed protocol for these methods be undertaken to facilitate further validation. Together, this information will allow for two types of risk assessment associated with respiratory allergy: the risk that exposure to a material will (1) induce sensitization in an individual and (2) elicit allergic reactions in a previously sensitized individual. PMID- 7982524 TI - Immunotoxicological investigation using pharmaceutical drugs: in vivo evaluation of immune effects. AB - Traditional methods for toxicological assessment have indicated that the immune system is a frequent target of toxic insult following subchronic or chronic exposure to xenobiotics. However, most of the xenobiotics evaluated in standardized protocols were environmental chemicals and correlation with available clinical data was not possible. The purpose of this work was to evaluate the potential immunosuppressive effects of pharmaceutical drugs using a standardized protocol developed for immunotoxicological assessment. Two groups of pharmaceutical drugs were utilized: (a) drugs without known immunosuppressive effect linked to their utilization in human therapy (cimetidine, furosemide, indomethacin, amoxicillin, and procainamide) and (b) immunosuppressive drugs (azathioprine, cyclosporine A, and dexamethasone). Ex vivo tests using B6C3F1 mice were performed after a 28-day repeat dose regimen and assessed: (a) immunopathology, (b) cell-mediated immunity, (c) humoral immunity, and (d) nonspecific immunity. Host resistance to Listeria monocytogenes was also assessed following exposure to immunosuppressive drugs. The results showed that (a) immunopathology and immune function assays were necessary to detect all immunotoxicants and (b) the effects observed with nonimmunotoxic drugs were sometimes statistically significant but the biological significance of these effects is unlikely. PMID- 7982525 TI - Subchronic inhalation toxicity studies with hydrochlorofluorocarbon 123 (HCFC 123). AB - Hydrochlorofluorocarbon 123 (HCFC 123) is one of the chemicals being considered as a replacement for the chlorofluorocarbons. Four subchronic inhalation toxicity studies from 1 to 3 months in duration have been conducted with HCFC 123. One study utilized rats and dogs, while the others were limited to rats only. The exposure levels have ranged from 300 ppm up to 20,000 ppm. Although the studies were conducted over a 14-year period, the results were consistent. In all studies, increases in liver weights were seen at 1000 ppm and above; additionally, one showed this effect at 500 ppm. Histopathological findings were minimal, consisting primarily of focal necrosis in the liver of the dogs at 10,000 ppm. Induction of peroxisomal activity, lowering of serum cholesterol and triglyceride levels, and an increase in urinary fluoride levels were also seen. The 4-hr LC50 in the rat has been reported as 35,000 ppm. At 20,000 ppm for 6 hr, the total daily dose on a concentration times time basis is almost equal to the LC50, yet, in the 4-week study, with 20 exposures at this level, there was no mortality or even marked signs of toxicity. There appeared to be no evidence for cumulative toxicity from multiple exposures in these studies. Overall, HCFC 123 appears to have a low level of toxicity by the inhalation route. PMID- 7982526 TI - Screening petrochemicals for contact hypersensitivity potential: a comparison of the murine local lymph node assay with guinea pig and human test data. AB - Over the last few years, the Murine Local Lymph Node Assay (MLLNA) has received considerable attention as a more quantitative, less expensive alternative to the guinea pig assays currently employed to identify potential human contact allergens. At this time, several companies are involved in both independent and joint efforts to validate the MLLNA with their products. This report describes the preliminary results of an Exxon-sponsored research effort to validate the assay with selected materials that are representative of our company's diverse chemical and petroleum product groups. Nine test materials were chosen for which there already existed guinea pig and/or human patch sensitization data. When the MLLNA results were compared to those data obtained from currently used predictive tests (guinea pig, human patch test), the MLLNA showed good agreement for moderate and strong sensitizers. However, the assay may be prone to the potential confounding effects of irritation (false positives), may be insensitive to weak sensitizers, and may be influenced by vehicle selection. PMID- 7982527 TI - Gender-specific effects of prenatal chlordane exposure on myeloid cell development. AB - Work previously reported by this laboratory indicated that prenatal chlordane exposure affected macrophage function in young adult mice. Because these macrophage effects were due to exposure during the development of the immune system, the possibility of a persistent effect on the development of myeloid stem and progenitor cells was considered. Female mice were treated with either 0 or 8 mg of chlordane per kilogram body weight daily for 18 days during pregnancy. Myeloid hemopoietic activity of bone marrow cells from 6-week-old offspring was evaluated for in vitro colony-forming units-in-culture in response to exogeneously added recombinant forms of the cytokines granulocyte/macrophage colony stimulating factor, macrophage-CSF, and interleukin 3 (IL-3). There was a significant depression of the numbers of bone marrow colony forming units granulocyte/macrophage (CFU-GM), CFU-IL-3, and CFU-macrophage (CFU-M) in only the female offspring. Male offspring consistently demonstrated no difference in the CFU-GM, CFU-IL-3, or CFU-M. Prenatal treatment with chlordane did not significantly affect the number of recoverable viable bone marrow cells in either male or female mice. PMID- 7982528 TI - A developmental neurotoxicity evaluation of the effects of prenatal exposure to fluoxetine in rats. AB - Fluoxetine is a widely used serotonin reuptake inhibitor effective in the treatment of depression. This experiment assessed the potential developmental neurotoxicity of fluoxetine. Sprague-Dawley CD rats were treated once per day on Days 7-20 of gestation with 0, 1, 5, or 12 mg/kg of fluoxetine (free base) dissolved in distilled water. One control group received water by gavage; animals in this group were provided food and water ad libitum. The second control group (PF) also received water by gavage; animals in this group had their food and water restricted by pair-feeding and watering them to the 12 mg/kg fluoxetine group. Litters were culled to 12 after birth and offspring (male/female pairs) were tested neurobehaviorally at three developmental stages (preweaning, juvenile, and adult). At each stage, two pairs per litter received tests of locomotor activity, acoustic startle, and startle after administration of one of two pharmacological challenges (one pair each receiving fluoxetine or apomorphine). Two pairs were also tested for spontaneous alternation, passive avoidance, and complex learning in a water maze. At the highest dose, fluoxetine caused maternal weight loss during pregnancy, reduced litter sizes at birth, and increased neonatal mortality. No effects on long-term growth or survival were seen. Prenatal fluoxetine exposure produced no significant effects on locomotor activity, spontaneous alternation, passive avoidance, or water maze performance. A few scattered interactions involving treatment group were obtained on startle, but no pattern of treatment-related changes was evident. Regional wet and dry brain weights taken at each stage were not affected by prenatal fluoxetine exposure. The data suggest that fluoxetine is not developmentally neurotoxic in the rat. PMID- 7982529 TI - Chronic toxicity and oncogenicity study with vinyl acetate in the rat: in utero exposure in drinking water. AB - The purpose of this study was to evaluate vinyl acetate for potential chronic toxicity and oncogenicity when given to rats in drinking water from the time of gestation. Target concentrations were 0, 200, 1000, and 5000 ppm (v/v). Drinking water solutions were prepared daily and analyzed at approximately 4-week intervals. F0 rats were given solutions of vinyl acetate for 10 weeks and then mated. Offspring (F1 rats) were culled to equal group sizes of 60 main study rats and 30 rats for satellite groups. F1 rats were treated for up to 104 weeks with interim kills of satellite groups at 52 and 78 weeks. Body weights and clinical signs of toxicity were monitored in F0 and F1 rats. Food and water consumption were measured in F1 rats. At Weeks 52 and 78 of the test, clinical pathology and urine analysis examinations were conducted on 10 rats per group from satellite animals. A complete gross and histopathological examination of F1 rats was conducted at the interim kills and on main study rats at Week 104. Average vinyl acetate consumption over the course of the study in male rats of the 200, 1000, and 5000 ppm groups was 10, 47, and 202 mg/kg/day, respectively. Female rats consumed an average of 16, 76, and 302 mg/kg/day, respectively. Compound-related effects observed during the study included a concentration-related decrease in water consumption among rats of the 1000 and 5000 ppm groups and a decrease in food consumption among rats of the 5000 ppm groups. Concurrent body weight decrement was observed only in the 5000 ppm groups.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7982530 TI - Chronic toxicity and oncogenicity inhalation study with vinyl acetate in the rat and mouse. AB - Vinyl acetate was evaluated for chronic toxicity and oncogenicity in male and female rats and mice in a 104-week study. Target concentrations were 0, 50, 200, and 600 ppm. The study included interim terminations at approximately 53 and 83 weeks and a group whose exposure was terminated at 70 weeks and allowed a 15-week recovery period. Over the course of the exposures, body weight gain was consistently depressed in all 600 ppm groups and in the 200 ppm mice. Except for female rats of the 600 ppm exposure group, recovery animals showed significant improvements in weight gain relative to controls. There were no changes in hematological parameters of either species that could be unequivocally related to treatment. The only effect noted on clinical chemical parameters during the study were decreases in blood glucose in the 600 ppm females. There were no adverse effects on survival in either species. Increases in lung weight were noted in rats and mice primarily in the 600 ppm groups. These changes were associated with bronchial exfoliation, macrophage accumulation, and fibrous plaques and buds extending into the airway lumen, and bronchial/bronchiolar epithelial disorganization. The most significant histopathological changes were noted in the nasal cavity. In the olfactory epithelium of both rats and mice, the main nonneoplastic changes included epithelial atrophy, regenerative effects (squamous metaplasia and respiratory metaplasia of olfactory epithelium), basal cell hyperplasia, and epithelial nest-like infolds. No nonneoplastic changes were observed in the respiratory epithelium of rats, while squamous metaplasia at the naso/maxilloturbinate region was prevalent in mice. Nonneoplastic changes were similar in the recovery groups. Oncogenic responses to vinyl acetate exposure were mainly confined to the nasal cavity in rats and included endo- and exophytic papillomas, squamous cell carcinoma, carcinoma in situ in olfactory regions, and endophytic papilloma in respiratory regions. Squamous cell carcinomas were also found either in areas normally covered by cuboidal epithelium or areas of unknown origin. One squamous cell carcinoma was found in the larynx of a rat of the 600 ppm groups. One squamous cell carcinoma was found in the lung of a mouse of the 600 ppm group.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 7982531 TI - The predictive accuracy of in vitro measurements for the dermal absorption of a lipophilic penetrant (fluazifop-butyl) through rat and human skin. AB - The predictive accuracy of in vitro measurements in estimating dermal absorption has been evaluated in rat and human skin using fluazifop-butyl (FB), a lipophilic model compound, at dosage rates of 2.5, 25, and 250 micrograms/cm2. In vitro studies used rat and human epidermal membranes mounted in static diffusion cells with radiolabeled FB and receptor fluids of 50% aqueous ethanol (Aq Et), 6% polyethylene glycol 20 oleyl ether in saline (PEG), or tissue culture medium (TCM). In vivo rat studies with radiolabeled FB were carried out to parallel previously published human volunteer studies. For rat skin, in vitro measurements with all types of receptor fluid provide an adequate prediction (generally within a factor of 3) of in vivo absorption. Absorption data for human epidermal membranes with a receptor fluid of Aq Et were adequately predictive of the in vivo absorption. In contrast, membranes with PEG or TCM significantly underestimated the in vivo absorption. The results support the conclusion that in vitro studies are useful to predict in vivo dermal absorption in rat and man, when appropriate receptor fluids are used. PMID- 7982532 TI - Short-term toxicity of bitumen upgrading products in the rat following repeated dermal exposure. AB - Light gas oil (B-LGO), heavy gas oil No. 1 (B-HGOI), and heavy gas oil No. 2 (B HGOII) fractions of bitumen upgrading products (BUPs) were applied on the dorsal skin of rats at 25 mg/kg bw/day (low dose), 100 mg/kg bw/day (intermediate dose), and 400 mg/kg bw/day (high dose) for 4 weeks. Control animals received normal saline while positive controls received a medium boiling coal liquefaction product (CLP) at 100 and 400 mg/kg bw/day. Reduced food comsumption and growth suppression were observed in males and females treated with B-HGOI, B-HGOII, and CLP, but only in males receiving B-LGO. Increased relative spleen, kidney, and liver weights were observed in animals treated with B-HGOI, B-HGOII, and CLP, but not in control or LGO groups. A dose-related increase in absolute and relative liver weight was most marked in animals receiving B-HGOII where a significant increase was observed starting at the low dose, followed by those receiving B HGOI and CLP. Appearance of pale foci on the splenic capsule and increases in spleen/body weight ratio were limited to animals receiving B-HGOI and B-HGOII. Decreases in hematocrit and RBC and increase in percentage of reticulocytes were observed in animals of both sexes receiving B-HGOI and B-HGOII. Female rats appeared to be more severely affected because significant decreases in hemoglobin and RBC were observed in animals receiving the low dose of B-HGOII and the intermediate dose of B-HGO-I. Increased serum cholesterol was observed in B-HGOII treated females at all dose levels, and in males starting at the intermediate dose. Histological changes were observed in the thymus gland, where moderate to marked cortical atrophy was noted in male and female rats receiving the high dose of B-HGOI and B-HGOII, and in the bone marrow, where the most significant abnormality was the presence of focal myelofibrosis in some male rats treated with B-HGOI and B-HGOII. Mild to moderate histological changes were found in the thyroid, liver, and spleen of rats of all treatment groups. Changes in the skin included moderate hyperkeratosis in females receiving high doses of B-LGO and in animals of both sexes receiving high doses of B-HGOI, and moderate to marked epidermal hyperplasia in rats receiving high doses of B-HGOI.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 7982533 TI - Evaluation of exposure to water aerosol or air by nose-only or whole-body inhalation procedures for CD-1 mice in developmental toxicity studies. AB - This study was performed to evaluate the effects of nose-only restraint versus whole-body exposure procedures in the absence of test chemical, and to determine the appropriate control environment (water aerosol or air) for subsequent developmental toxicity studies of test materials administered as aerosols. Timed pregnant CD-1 mice, 30/group, were exposed to high concentrations of water aerosol or to air by whole-body or nose-only inhalation procedures on Gestational Days (GD) 6 through 15 for 6 hr per day. The group exposed to air by whole-body procedures was designated as the control group. Clinical observations and maternal body weights were recorded throughout gestation. At scheduled necropsy on GD 18, maternal animals were evaluated for body weight, gravid uterine weight, liver weight, number of ovarian corpora lutea, and status of uterine implantation sites. Fetuses were counted, weighed, and sexed and were examined for external, visceral (including craniofacial), and skeletal alterations. Indices of maternal toxicity were affected in both nose-only groups. Maternal body weights were reduced during and after the exposure period; maternal weight gain was reduced during the exposure period. Clinical signs observed, from animals struggling during restraint, were resolved by GD 18. At sacrifice on GD 18, maternal body weights and maternal gestational weight gains (both corrected for gravid uterine weights) and absolute liver weights were reduced in both nose-only groups. Four females died (13.3%, all pregnant) in the air nose-only group, and maternal liver weight (relative to body weight) was reduced in the aerosol nose-only group. Gestational parameters were unaffected by any of the treatments. There were no statistically significant differences in the incidences of any individual malformations or malformations by category (external, visceral, or skeletal) or of total malformations. However, exencephaly, low set ears, cleft palate and ventricular septal defect were observed only in both aerosol-exposed groups (whole-body and nose-only exposed). The incidences of individual external or visceral variations or of variations by category or of total variations were unaffected. The incidence of one skeletal variation, poorly ossified supraoccipital skull bone, was significantly increased in the aerosol nose-only group relative to the air whole-body controls. There were also increased incidences (not statistically significant) of extra (14th) ribs in both aerosol groups. Therefore, maternal restraint (in both nose-only groups) during organogenesis produced indications of maternal toxicity, but restraint did not appear to affect normal embryo/fetal morphologic development.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 7982534 TI - Increased frequency of resistance to terminal differentiation in C3H mouse cells produced by genotoxic but not nongenotoxic carcinogens. AB - Certain cells present in mouse skin are resistant to calcium-induced terminal differentiation. It is believed that these calcium-resistant cells (CRCs) represent an early stage in the carcinogenic process, in part, because frequency increases after treatment with mutagens. The frequency of CRCs in C3H mouse skin was measured before and after treatment with certain petroleum-derived materials. One objective was to determine whether this assay could differentiate between genotoxic and nongenotoxic mouse skin carcinogens. An additional objective was to determine whether CRCs are an important factor in the tumorigenicity of petroleum middle distillates (PMDs), a class of apparently nongenotoxic mateials. Three petroleum-derived materials were tested: mineral oil (MO), a noncarcinogenic product used as the negative control; catalytically cracked clarified oil (CCCO), a highly carcinogenic and mutagenic material; and a lightly paraffinic (LRPO), a PMD which has produced tumors when repeatedly applied, but is not mutagenic and does not initiate most skin tumors. The CRC frequency was not increased by LRPO treatment; however, a statistically significant and dose-related increase was produced by CCCO. These results are consistent with observations that genotoxic, petroleum-derived liquids are capable of tumor initiation in mouse skin, whereas PMDs which are not genotoxic do not initiate skin tumors. The number of CRCs in untreated and MO-treated mice was approximately twice the tumor frequency measured in bioassays of PMDs. Thus, tumor production associated with these products could be due to promotion of preexisting, spontaneously initiated cells. PMID- 7982535 TI - Chronic toxicity/oncogenicity of dimethylformamide in rats and mice following inhalation exposure. AB - The potential chronic toxicity and oncogenicity of dimethyl-formamide (DMF) was evaluated by exposing male and female rats and mice to 0, 25, 100, or 400 ppm DMF for 6 hr/day, 5 days/week for 18 months (mice) or 2 years (rats). Clinical pathology was evaluated at 3, 6, 12, 18, and 24 (rats only) months. An interim euthanasia for rats occurred at 12 months and hepatic cell proliferation in rats and mice was examined at 2 weeks, 3 months, and 12 months. No compound-related effects on clinical observations or survival were observed. Body weights of rats exposed to 100 (males only) and 400 ppm were reduced. Conversely, body weights were increased in 400 ppm mice. No hematologic changes were observed in either species. Serum sorbitol dehydrogenase activity was increased in rats exposed to 100 or 400 ppm. There were no compound-related effects on the estrous cycle of rats or mice at any concentration. Compound-related morphological changes were observed only in the liver. In rats, exposure to 100 and 400 ppm produced increased relative liver weights, centrilobular hepatocellular hypertrophy, lipofuscin/hemosiderin accumulation in Kupffer cells, and centrilobular single cell necrosis (400 ppm only). In mice, increased liver weights (100 ppm males, 400 ppm both sexes), centrilobular hepatocellular hypertrophy, accumulation of lipofuscin/hemosiderin in Kupffer cells, and centrilobular single cell necrosis were observed in all exposure groups. These observations occurred in a dose response fashion and were minimal at 25 ppm. No increase in hepatic cell proliferation was seen in mice or female rats. Slightly higher proliferation was seen in male rats exposed to 400 ppm at 2 weeks and 3 months but not at 12 months. Dimethylformamide was not oncogenic under these experimental conditions in either the rat or mouse. PMID- 7982536 TI - Carcinogenicity studies of oxazepam in mice. AB - Oxazepam is a benzodiazepine widely used as a sedative-hypnotic and antianxiety drug. In chronic studies, groups of 60 male and 60 female Swiss-Webster (SW) or B6C3F1 mice received oxazepam in feed at concentrations of 0,2500, or 5000 ppm. Additional groups of 60 male and female B6C3F1 mice received 125 ppm in feed to allow for study of mice with serum concentrations of oxazepam similar to those achieved in humans taking a therapeutic dose. At 57 weeks, treatment-related mortality of exposed SW mice caused the study to be terminated. Enhanced systemic amyloidosis contributing to heart failure was considered the principal cause of death. Hepatocellular adenomas and carcinomas were increased in exposed SW mice. Survival of B6C3F1 mice receiving 2500 and 5000 ppm oxazepam was also lower than that of controls. Early deaths were due to increased incidences of hepatoblastoma and hepatocellular carcinoma, and nearly all mice receiving 2500 or 5000 ppm developed hepatocellular neoplasia. An increase in follicular cell hyperplasia of the thyroid gland occurred in all exposed groups of B6C3F1 mice, and thyroid gland follicular cell adenoma was increased in exposed females. Further studies of the capacity of oxazepam to induce liver cell mitogenesis and an evaluation of the frequency of activated H- and K-ras oncogenes in the liver tumors of B6C3F1 mice has shown that many of the neoplastic and nonneoplastic responses of mice to oxazepam resemble those observed with phenobarbital. PMID- 7982537 TI - Induction of peroxisomal enzymes by a tetrazole-substituted 2-quinolinylmethoxy leukotriene D4 antagonist. AB - The induction of hepatic peroxisomal beta-oxidation and the peroxisomal bifunctional enzyme (PBE) by the tetrazole-substituted leukotriene D4 receptor antagonist RG 7152 was evaluated in vivo following subchronic treatment in the mouse, rat, guinea pig, dog, and rhesus monkey. The ability of RG 7152 to induce this enzyme system in rat extrahepatic tissues reported to respond to peroxisome proliferators and in vitro in primary rat hepatocytes was also investigated. Western blot analysis for PBE and beta-oxidation assays revealed significant induction by RG 7152 in liver homogenates from rats and mice with a lesser effect in guinea pigs and monkeys and no effect in dogs. The degree of induction in rat liver was less than that observed in a positive control group treated with clofibrate (CF). There was slight induction of PBE in rat kidney and small intestine by CF, whereas RG 7152 elicited a minimal response in the kidney and no effect in the small intestine. In vitro, RG 7152 produced a response that was greater than that produced by diethylhexyl phthalate, approximately equivalent to that produced by clofibric acid, but less than that produced by bezafibrate. Dose response comparison of RG 7152 with the tetrazole-substituted leukotriene D4 antagonist LY 171883 to be slightly more potent than RG 7152. Thus, RG 7152 represents a second chemical class of tetrazole-substituted leukotriene D4 antagonist that causes peroxisomal enzyme induction in rodents. PMID- 7982538 TI - Detection of DNA adducts by 32P-postlabeling and multifraction contact-transfer thin-layer chromatography. AB - 32P-Postlabeling is a sensitive method for detecting DNA adducts. Large bulky adducts, particularly from polycyclic aromatic compounds, are readily detected using this technique. Detection of small modifications, such as methylations, has often required specific additional enrichment procedures prior to 32P postlabeling. We report the use of a single analytical procedure that can detect DNA adducts of a wide range of sizes and hydrophobicities (exemplified by adducts produced with methyl methanesulfonate, diepoxybutane, styrene oxide, or benzo[a] pyrene). This 32P-postlabeling/thin-layer chromatography procedure is particularly useful when examining the potential of novel compounds or their metabolites to form DNA adducts. PMID- 7982539 TI - Re: Neurobehavioral screening approach to study of toxicity of 3,3' iminodipropionitrile. PMID- 7982540 TI - [Experiences in publication of a medical specialty periodical: Obstetrics and Gynecology]. PMID- 7982541 TI - [Infertility--trends in psychosomatic research]. PMID- 7982542 TI - [7 years ambulatory gynecologic surgery--a report of experiences]. PMID- 7982543 TI - [Diagnosis and therapy of congenital toxoplasmosis]. PMID- 7982544 TI - [The positive "vocal fremitus" in malignant breast tumors in color MEM ultrasound imaging--an exciting artifact in confirming the diagnosis?]. AB - In the experimental phase of application of a new Non-Doppler technology (MEM system, Acoustic Imaging, Phoenix; Dornier Medizintechnik) we observed, that in patients, who spoke during colour imaging of a breast tumour, artifacts appeared in or around the lesion: the colour artifacts were seen regularly inside the tumour in cases of malignancies, and exactly surrounding benign tumours. Postoperative histological findings served as an objective criterion of classification/differentiation. To examine this phenomenon, we performed a study in 71 patients. These women with a sonographically detectable tumour (37 malignant, 34 benign) were examined on the day before surgery. We observed, that if patients uttered the number "99" with a relatively low voice or alternatively hummed a deep sound, the artifacts could be regularly visualized. In 66/71 patients (93%) status evaluation by artifact generation due to vocal fremitus examination was correct. In 3 patients the tumour was erroneously described as malignant, histology showing a proliferative mastopathy. In 2 cases the tumour was classified as benign, whereas histology revealed a malignancy, in both patients a large ductal-invasive carcinoma (> 3 cm). This phenomena could, however, not be reproduced with other colour techniques. A possible explanation is: Thoracic vibrations during speech can be registered by the MEM technique. These vibrations are not perpetuated into the benign lesion characterised by a displacing growth, due to which the vibrations are "barred off" at the borders of the tumour. Infiltrating growth typical of a malignancy causes transmission of these vibrations into the center of the tumour.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7982545 TI - [New perspectives in color ultrasound in breast diagnosis]. AB - In recent years, ultrasound has become established as part of the diagnostic evaluation of breast tumours. Not replacing, but complementing mammography, ultrasonic investigations increasingly represent a sensitive means of early diagnosis. Thermography, on the other hand, has proved of relatively little value and doesn't play a significant role today. Lately, Colour Doppler sonography has been used for differentiating tumour-associated blood supply patterns--however, sensitivity and specificity were not as high as initially expected. Colour spectrum analysis of local findings in comparison to the remaining glandular tissue, however, seems to be a promising method in the differentiation of ultrasound findings of uncertain tumour status. A fibroadenoma shows no significantly different colour density as compared to surrounding tissue. In carcinoma, on the other hand, one regularly finds a hyperintensive zone with sharp margins. In 70 patients, who had breast tumours, we attempted the differentiation of benign and malignant findings with the help of colour spectrum analysis. Postoperatively, these results were validated by histology. With the exception of one mesenchymal tumour, the Doppler diagnosis was identical to the histopathological findings. PMID- 7982546 TI - [Safety and effectiveness of endosurgical management of benign adnexal tumors in the premenopausal period: a prospective study]. AB - Between January 1985 and December 1989, a prospective laparoscopic study was performed in premenopausal women with pelvic cysts growing or persisting for at least three months or evoking acute abdominal complaints. The aim of this prospective study was the investigation of the functional/nonfunctional rate, the relapse and the malignancy rate. 372 women underwent a diagnostic-operative laparoscopy in the absence of irregular solid and cystic parts detectable by preoperative vaginal ultrasonography. The treatment consisted of non-randomised endosurgical ovarian cystostomy, cystectomy or ovarectomy. Histopathological assessment showed functional ovarian cysts in 268 women and non-functional benign ovarian tumours in 104. 2 cases were subsequently found to be malignant. After a mean follow-up-time of at least one year, we found an overall recurrence rate of 4.6% after cystostomy, 2% after cystectomy and 0% after ovarectomy in the group of functional ovarian cysts and a total of 1% after endosurgical therapy of the non-functional ovarian tumours. The diagnostic operative laparoscopy proved to be a safe and efficient treatment of pelvic cysts in women of reproductive age, provided a sufficient preoperative vaginal ultrasound examination had been performed. PMID- 7982547 TI - [Diagnosis and therapy of adnexal tumors in postmenopause. A prospective study]. AB - The management of postmenopausal adnexal tumours is still controversially discussed. Approximately 30% of all postmenopausal tumours are malignant. The standard operative approach for these adnexal masses is still the exploratory laparotomy although the advantages of laparoscopic procedure are obvious, even in older patients. The aim of this prospective study was to find out to what extent diagnostic-operative laparoscopy is able to replace laparotomy in the therapy of postmenopausal adnexal masses. From January 1990 to August 1992, 169 postmenopausal patients entered the prospective study. After careful preoperative diagnostics, 63 patients underwent a laparotomy (group B) and 106 patients a laparoscopy (group A). 10 of these 106 cases underwent laparotomy after diagnostic laparoscopy (group Ab). The main operative procedure in group Aa was laparoscopic adnexectomy after Semm. Mean operative time and mean postoperative hospital stay were significantly lower in patients, who only underwent laparoscopic operation (group Aa). One case (0.9%) of the laparoscopically operated patients was subsequently found to be malignant (histologic assessment) and immediately treated by laparotomy with hysterectomy and contralateral adnexectomy. The combination of vaginal examination, vaginal/abdominal ultrasonography (tumor marker CA 125) and a sufficient preoperative diagnostic during endosurgery (no proliferations on the ovary or peritoneal surface, no ascites) reduces the risk of operating a malignant tumour by laparoscopy to a minimum. We believe that operative laparoscopy of postmenopausal adnexal masses is a safe and efficient method in carefully selected women. PMID- 7982548 TI - [The effect of tubal sterilization on ovarian function]. AB - Disturbances of menstrual cycle, as well as premature onset of climacterial symptoms, are discussed as late complications of diverse techniques of tubal sterilisation. A disturbance of the ovarian function is regarded as cause for the disorder known as "post-tubal ligation syndrome". This study should help to clarify if tubal sterilisation via bipolar high-frequency current influences the course of perimenopause. 109 patients were examined, who had been sterilised by this technique at the Department of Gynaecology and Obstetrics of the University of Cologne during the period 1980 to 1984. 103 patients formed the comparison group, all of whom had neither undergone tubal sterilisation nor hysterectomy. The age of these women of both groups ranged between 36 and 51. Patients of both groups were interviewed personally with regard to cycle irregularities, climacteric symptoms, and onset of menopause in the form of transverse examination. Simultaneously, blood tests were performed to establish the endocrinological status, and to examine FSH and 17-beta-oestradiol levels. Summing up, this study led to the following conclusions: 1. Menstrual disturbances, climacteric symptoms after tubal sterilisation during perimenopause do not occur more frequently than in a comparative group of the same age. 2. In comparison with a group of women with no surgical history, neither did cycle anomalies and ovarian deficiency symptoms in terms of climacteric complaints occur earlier, nor did early onset of menopause take place more often in this examined group of sterilised women. 3. Hormone analysis could not establish any significant differences between both groups in respect of endocrinological parameters in the perimenopause.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7982549 TI - [Peri- and postoperative quality of life in pelviscopy and laparotomy]. AB - In 298 patients we evaluated criteria of peri- and post-operative quality of life. 222 patients underwent pelviscopic surgery and 76 patients underwent laparotomy. The parameters of convalescence used were: the duration of hospital stay and disablement, the duration and intensity of post-operative discomfort, and the number of consultations in a physician's office after discharge from hospital. Our results show, that minimal access endoscopic surgery can reduce the impairment in the peri- and post-operative quality of life. PMID- 7982550 TI - [Is there a correlation between tubal occlusions in chronic salpingitis and urogenital chlamydia infections?]. AB - A prospective study was performed to analyse the relationship between urogenital infections caused by Chlamydia trachomatis and occlusions of the fallopian tubes with histologically confirmed chronic salpingitis and salpingitis isthmica nodosa. 110 infertile patients were tested for C. trachomatis infection. 23 patients with tubal occlusions and histologically confirmed chronic salpingitis (group 1) and eight patients with salpingitis isthmica nodosa (group 2) were compared to 13 patients with tubal occlusions after tuboligation (group 3), and to 66 patients with patent fallopian tubes as demonstrated by laparoscopy or hysterosalpingography (group 4). The prevalence of infections of the endocervix or urethra and the presence of Chlamydia in urine was low in all four groups. However, in groups 1 and 2, the median Chlamydia IgG and IgA serum antibody titres were significantly higher (p < or = 0.0002) than in groups 3 and 4. This result illustrates the association between urogenital infections with Chlamydia and tubal occlusions with histologically documented chronic salpingitis and salpingitis isthmica nodosa. PMID- 7982551 TI - [Ultrasound detection of suspected chromosome abnormalities in the 1st and 2nd trimester. Results of a prospective study]. AB - 4053 pregnancies were studied prospectively during 4 years (July 1988 to June 1992) with regard to the sonographical recognition of indications of chromosomal anomalies from 9 to 24 weeks, irrespective of the mother's age. The morphology of the fetal organs, the phenotype, the proportions of the fetal body, biometrical data and disorders of the placenta and the amniotic fluid were scrutinised. For the prediction of a chromosomal anomaly, a high sensitivity of 86.3% and specificity of 99.8% were found; the prevalence was 1.8%. The thickening of the nuchal fold or a nuchal oedema was the most significant fetal stigma and a guiding symptom in Turner's syndrome and in trisomy 21 and 18. When suspicious facts were found during ultrasonography, karyotyping was proposed after detailed counselling, especially to mothers below the age of 35. The extended sonographical examination is considered a non-invasive tool to differentiate the statistical age related risk of a chromosomal anomaly in each individual case. PMID- 7982552 TI - [Prenatal diagnosis of severe stenosis of the ductus arteriosus Botalli in a twin pregnancy]. AB - Premature ductus arteriosus stenosis is a rare cardiovascular disease, which has a poor prognosis. The case presented was detected even in early pregnancy and was progressed rapidly to the stage of severe foetal heart failure. The patient was first seen at 20 weeks of gestation with one of the foetuses of a twin pregnancy, showing signs of cardiac decompensation and advanced hydrops fetalis universalis. Obstruction of the ductus arteriosus may result from maternal tocolysis treatment with prostaglandin synthetase inhibitors, such as indomethacin or maternal salicylate or in conjunction with foetal post maturity. PMID- 7982553 TI - [Hydrocephalus in one twin after massive reverse flow in the umbilical artery in the 2nd trimester]. AB - The case of a twin pregnancy with severe diastolic reverse flow in the umbilical artery of one of the twins at 23 weeks' gestation is reported. After delivery at 29 weeks' gestation, a congenital internal hydrocephalus was diagnosed in this twin. The most probable aetiology is an intrauterine periventricular haemorrhage. The severe diastolic reverse flow in the umbilical artery seems to represent a highly pathological flow pattern of prefinal degree, possibly leading to cerebral defects. The pathophysiology of the Doppler findings and the pathogenesis of the internal hydrocephalus are discussed. PMID- 7982554 TI - [Doppler ultrasound study of a twin pregnancy with feto-fetal transfusion syndrome]. AB - A report is made on a typical case of twin-twin transfusion syndrome of monozygotic twins with severe polyhydramnios. By treatment with decompression amniocentesis, we achieved prolongation of the pregnancy by 10 weeks. Daily performed Doppler velocimetry showed, that the resistance values did not differ before and after amniocentesis. We found the greatest differences between the pulsatility indices of the umbilical cords and the aortae. The arteriovenous anastomosis was visualized by colour flow mapping. PMID- 7982555 TI - [Inhuman practices in gynecology in national socialism and its victims. Study of concrete results]. AB - In our opinion German gynaecology has failed to adequately face what came to pass during the Nazi period. This can be proved objectively, for there is no evidence that, after 1945, gynaecology had in any way cared to take notice--either thermatically or medically--of the thousands of victims of inhuman practices such as forced termination of pregnancy, compulsory sterilisation and the like. During the past 50 years recollections of enforced sterilisations, compulsory abortions, deliberate and hence criminal negligence and problematic approaches in research and teaching were almost completely banished from the area of conscious awareness and largely suppressed or silently ignored. Most of the medical directors of Departments of Gynaecology of German universities shared this view whenever they were questioned on the connections between gynaecology and Nazism. Now that two generations have passed it seems possible to examine and explore with less guilt feelings and shame the immensely fateful role of gynaecology in that context. Accent should be on the fate of the victims of that period. To bring back these events to memory, however, does not permit to conceal the part played by the physicians committing of these inhuman Nazi crimes. Data collected from a psychosomatically oriented examination of victims exemplify that to concretely recall gynaecology during Nazism a1-so offers a chance in several respects. One of the possibilities in this context is to signal "late apology" and regret to patients who had been victims, in one's own area of work, after one has psychically worked over their fate. Besides, a gynaecological-psychosomatic expertise will help e.g. that compulsorily sterilised women are granted financial aid that has at long last become a legal possibility and can be applied for since 1980. However, the relevant patient records do show very clearly that the inhuman practice of gynaecology during the so-called "Third Reich" was not only a collective problem but equally due to a failure of the individual conscience of numerous gynaecologists. Working over this complex may enhance our own sensitivity for psychosomatic and ethic problems and counteract any likelihood of a recurrence of an inhuman gynaecology. PMID- 7982556 TI - Meiotic gene conversion tract length distribution within the rosy locus of Drosophila melanogaster. AB - Employing extensive co-conversion data for selected and unselected sites of known molecular location in the rosy locus of Drosophila. we determine the parameters of meiotic gene conversion tract length distribution. The tract length distribution for gene conversion events can be approximated by the equation P(L > or = n) = phi n where P is the probability that tract length (L) is greater than or equal to a specified number of nucleotides (n). From the co-conversion data, a maximum likelihood estimate with standard error for phi is 0.99717 +/- 0.00026, corresponding to a mean conversion tract length of 352 base pairs. (Thus, gene conversion tract lengths are sufficiently small to allow for extensive shuffling of DNA sequence polymorphisms within a gene). For selected site conversions there is a bias towards recovery of longer tracts. The distribution of conversion tract lengths associated with selected sites can be approximated by the equation P(L > or = n/ selected) = phi n(1 - n + n/phi), where P is now the probability that a selected site tract length (L) is greater than or equal to a specified number of nucleotides (n). For the optimal value of phi determined from the co-conversion analysis, the mean conversion tract length for selected sites is 706 base pairs. We discuss, in the light of this and other studies, the relationship between meiotic gene conversion and P element excision induced gap repair and determine that they are distinct processes defined by different parameters and, possibly, mechanisms. PMID- 7982557 TI - Molecular genetic analysis of the Drosophila melanogaster gene absent, small or homeotic discs1 (ash1). AB - The absent, small or homeotic discs1 gene (ash1) is one of the trithorax set of genes. Recessive loss of function mutations in ash1 cause homeotic transformations of imaginal disc derived tissue which resemble phenotypes caused by partial loss or gain of function mutations in genes of the Antennapedia Complex and bithorax Complex. F2 screens were used to isolate P element insertion alleles and EMS-induced alleles of ash1, including one temperature-sensitive allele, and an F1 screen was used to isolate gamma-ray-induced alleles. Analysis of ash1 mutant flies that survive until the adult stage indicates that not only imaginal disc- and histoblast-derived tissues are affected but also that oogenesis requires ash1 function. Mutations in the gene brahma (brm) which also is one of the trithorax set of genes interact with mutations in ash1 such that non-lethal ash1 +/+ brm double heterozygotes have a high penetrance of homeotic transformations in specific imaginal disc- and histoblast-derived tissues. The cytogenetic location of ash1 was determined to be 76B6-11 by the breakpoint of a translocation recovered in the F1 screen. The gene Shal, which is located cytogenetically nearby ash1, was used to initiate an 84-kb genomic walk within which the ash1 gene was identified. The ash1 gene encodes a 7.5-kb transcript that is expressed throughout development but is present at higher levels during the embryonic and pupal stages than during the larval stages. During the larval stages the transcript accumulates primarily in imaginal discs. During oogenesis the transcript accumulates in the nurse cells of developing egg chambers. PMID- 7982558 TI - string of pearls encodes Drosophila ribosomal protein S2, has Minute-like characteristics, and is required during oogenesis. AB - The first allele of string of pearls (sop) was isolated as a recessive female sterile mutant in a P element enhancer trap screen. Oogenesis in homozygous sop females arrests at approximately stage 5. In addition, homozygous flies of both sexes have Minute-like characteristics that include reduced bristles, delayed development and larval lethality. sop maps to 30D/E on chromosome 2L and encodes the Drosophila homolog of eukaryotic ribosomal protein S2. The gene is present in a single copy in the Drosophila genome and the level of mRNA present in mutant animals is reduced. The identification of a mutant allele that blocks development at a mid-stage of oogenesis may indicate that sop has a specific developmental role during oogenesis in addition to its general role in protein synthesis as a component of the small ribosomal subunit. PMID- 7982559 TI - The effects of mutation and natural selection on codon bias in the genes of Drosophila. AB - Codon bias varies widely among the loci of Drosophila melanogaster, and some of this diversity has been explained by variation in the strength of natural selection. A study of correlations between intron and coding region base composition shows that variation in mutation pattern also contributes to codon bias variation. This finding is corroborated by an analysis of variance (ANOVA), which shows a tendency for introns from the same gene to be similar in base composition. The strength of base composition correlations between introns and codon third positions is greater for genes with low codon bias than for genes with high codon bias. This pattern can be explained by an overwhelming effect of natural selection, relative to mutation, in highly biased loci. In particular, this correlation is absent when examining fourfold degenerate sites of highly biased genes. In general, it appears that selection acts more strongly in choosing among fourfold degenerate codons than among twofold degenerate codons. Although the results indicate regional variation in mutational bias, no evidence is found for large scale regions of compositional homogeneity. PMID- 7982560 TI - Weakener of white (Wow), a gene that modifies the expression of the white eye color locus and that suppresses position effect variegation in Drosophila melanogaster. AB - A locus is described in Drosophila melanogaster that modifies the expression of the white eye color gene. This trans-acting modifier reduces the expression of the white gene in the eye, but elevates the expression in other adult tissues. Because of the eye phenotype in which the expression of white is lessened but not eliminated, the newly described locus is called the Weakener of white (Wow). Northern analysis reveals that Wow can exert an inverse or direct modifying effect depending upon the developmental stage. Two related genes, brown and scarlet, that are coordinately expressed with white, are also affected by Wow. In addition, Wow modulates the steady state RNA level of the retrotransposon, copia. When tested with a white promoter-Alcohol dehydrogenase reporter. Wow confers the modifying effect to the reporter, suggesting a requirement of the white regulatory sequences for mediating the response. In addition to being a dosage sensitive regulator of white, brown, scarlet and copia, Wow acts as a suppressor of position effect variegation. There are many dosage sensitive suppressors of position effect variegation and many dosage-sensitive modifiers of gene expression. The Wow mutations provide evidence for an overlap between the two types of modifiers. PMID- 7982561 TI - Drosophila alcohol dehydrogenase polymorphism and carbon-13 fluxes: opportunities for epistasis and natural selection. AB - The influence of genetic variations in Drosophila alcohol dehydrogenase (ADH) on steady-state metabolic fluxes was studied by means of 13C NMR spectroscopy. Four pathways were found to be operative during 8 hr of ethanol degradation in third instar larvae of Drosophila. Seven strains differed by 18-25% in the ratio between two major pathway fluxes, i.e., into glutamate-glutamine-proline vs. lactate-alanine-trehalose. In general, Adh genotypes with higher ADH activity exhibit a twofold difference in relative carbon flux from malate into lactate and alanine vs. alpha,alpha-trehalose compared to low ADH activity genotypes. Trehalose was degraded by the pentose-phosphate shunt. The pentose-phosphate shunt and malic enzyme could supply NADPH necessary for lipid synthesis from ethanol. Lactate and/or proline synthesis may maintain the NADH/NAD+ balance during ethanol degradation. After 24 hr the flux into trehalose is increased, while the flux into lipids declines in AdhF larvae. In AdhS larvae the flux into lipids remains high. This co-ordinated nature of metabolism and the genotype dependent differences in metabolic flux may form the basis for various epistatic interactions and ultimately for variations in organismal fitness. PMID- 7982562 TI - Genetic instability at the agouti locus of the mouse (Mus musculus). I. Increased reverse mutation frequency to the Aw allele in A/a heterozygotes. AB - We have compiled the reverse mutation rate data to the white bellied agouti (Aw) allele in heterozygous A/a mice and shown it to be increased by a factor of at least 350 in comparison to the reverse mutation rate in homozygous a/a mice. Employing tightly linked flanking restriction fragment length polymorphism DNA markers, we have shown that reversion to Aw is associated with crossing over in the vicinity of the agouti locus. The non-agouti (a) allele has been recently shown to contain an 11-kb insert within the first intron of the agouti gene. Together with our present results, these observations suggest possible mechanisms to explain the reversion events. PMID- 7982563 TI - A primary linkage map of the porcine genome reveals a low rate of genetic recombination. AB - A comprehensive genetic linkage map of the porcine genome has been developed by typing 128 genetic markers in a cross between the European Wild Boar and a domestic breed (Large White). The marker set includes 68 polymerase chain reaction-formatted microsatellites, 60 anchored reference markers informative for comparative mapping and 47 markers which have been physically assigned by in situ hybridization. Novel multipoint assignments are provided for 54 of the markers. The map covers about 1800 cM, and the average spacing between markers is 11 cM. We used the map data to estimate the genome size in pigs, thereby addressing the total recombination distance in a third mammalian species. A sex-average genome length of 1873 +/- 139 cM was obtained by comparing the recombinational and physical distances in defined regions of the genome. This is strikingly different from the length of the human genome (3800-4000 cM) and is more similar to the mouse estimate (1600 cM). The recombination rate in females was significantly higher than in males. PMID- 7982564 TI - sin 1, a mutation affecting female fertility in Arabidopsis, interacts with mod 1, its recessive modifier. AB - In Arabidopsis thaliana, a mutation in the SIN 1 gene causes aberrant ovule development and female-specific sterility. The effect of the sin 1 mutation is polymorphic and pleiotropic in different genetic backgrounds. The polymorphism concerns morphology of the mutant ovules. The pleiotropism involves internodal distance and inflorescence initiation time. The particular ovule phenotype and the length of internodes are dependent on an interaction of sin 1 with a second recessive gene, which we term mod 1. The recessive mod 1 allele in a homozygous sin 1 mutant plant reduces internode length and ovule integument size. The mutation sin 1, but not mod 1, has a demonstrable effect on ovule morphology when acting independently. In our crosses mod 1 was inseparably linked to the well known mutation erecta that is known to cause a reduction in internode and pedicle lengths. PMID- 7982565 TI - Isolation of deficiencies in the Arabidopsis genome by gamma-irradiation of pollen. AB - Chromosomal deficiencies are a useful genetic tool in fine-scale genetic mapping and the integration of physical and visible marker genetic maps. Viable overlapping deficiencies may permit gene cloning by subtractive procedures and provide a means of analyzing the functional importance of different chromosomal regions. A method is described for isolation of deficiencies in the Arabidopsis genome which encompass specific loci and other extended chromosomal regions. The technique employs pollen mutagenized by gamma-irradiation to pollinate marker lines homozygous for recessive mutations. Deficiencies at specific loci were detected by screening for marker phenotypes in the F1. Screening for lethal mutations in the F1/F2 confirmed specific deficiencies and revealed other deficiencies that did not overlap the marker loci. Further evidence for such mutations was provided by distorted F2 segregation of the chromosomal markers linked to putative deficiencies. Maintainable (transmissible) and non transmissible deficiencies were demonstrated by their pattern of inheritance in subsequent generations. PMID- 7982566 TI - Genetic linkage maps of Eucalyptus grandis and Eucalyptus urophylla using a pseudo-testcross: mapping strategy and RAPD markers. AB - We have used a "two-way pseudo-testcross" mapping strategy in combination with the random amplified polymorphic DNA (RAPD) assay to construct two moderate density genetic linkage maps for species of Eucalyptus. In the cross between two heterozygous individuals many single-dose RAPD markers will be heterozygous in one parent, null in the other and therefore segregate 1:1 in their F1 progeny following a testcross configuration. Meiosis and gametic segregation in each individual can be directly and efficiently analyzed using RAPD markers. We screened 305 primers of arbitrary sequence, and selected 151 to amplify a total of 558 markers. These markers were grouped at LOD 5.0, theta = 0.25, resulting in the maternal Eucalyptus grandis map having a total of 240 markers into 14 linkage groups (1552 cM) and the paternal Eucalyptus urophylla map with 251 markers in 11 linkage groups (1101 cM) (n = 11 in Eucalyptus). Framework maps ordered with a likelihood support > or = 1000:1 were assembled covering 95% of the estimated genome size in both individuals. Characterization of genome complexity of a sample of 48 mapped random amplified polymorphic DNA (RAPD) markers indicate that 53% amplify from low copy regions. These are the first reported high coverage linkage maps for any species of Eucalyptus and among the first for any hardwood tree species. We propose the combined use of RAPD markers and the pseudo testcross configuration as a general strategy for the construction of single individual genetic linkage maps in outbred forest trees as well as in any highly heterozygous sexually reproducing living organisms. A survey of the occurrence of RAPD markers in different individuals suggests that the pseudo-testcross/RAPD mapping strategy should also be efficient at the intraspecific level and increasingly so with crosses of genetically divergent individuals. The ability to quickly construct single-tree genetic linkage maps in any forest species opens the way for a shift from the paradigm of a species index map to the heterodox proposal of constructing several maps for individual trees of a population, therefore mitigating the problem of linkage equilibrium between marker and trait loci for the application of marker assisted strategies in tree breeding. PMID- 7982567 TI - Fluctuation tests: how reliable are the estimates of mutation rates? AB - Fifty one years ago, Luria and Delbruck published in Genetics a paper that was to become a classic. In it they proved, beyond all reasonable doubt, that bacteria were mutating to phage resistance long before they could have encountered any bacteriophage. Luria and Delbruck also showed how the same experimental data could be used to estimate bacterial mutation rates. Since that time and in many different contexts the methods that they introduced have been used to estimate mutation rates. However, little seems to be known about the errors to be expected in such estimates. In what follows I examine how much uncertainty in the estimates is to be expected merely on the basis of the stochastic variability inherent in the sampling process. On the basis of this examination I question a few traditional ideas and conclude with some practical suggestions. The results were obtained by stimulation. It is my hope that they may inspire others to provide a rigorous theoretical basis for such calculations. PMID- 7982568 TI - Effective population sizes with multiple paternity. AB - While the concept of effective population size is of obvious applicability to many questions in population genetics and conservation biology, its utility has suffered due to a lack of agreement among its various formulations. Often, mathematical formulations for effective sizes apply restrictive assumptions that limit their applicability. Herein, expressions for effective sizes of populations that account for mating tactics, biases in sex ratios, and differential dispersal rates (among other parameters) are developed. Of primary interest is the influence of multiple paternity on the maintenance of genetic variation in a population. In addition to the standard inbreeding and variance effective sizes, intragroup (coancestral) and intergroup effective sizes also are developed. Expressions for effective sizes are developed for the beginning of nonrandom gene exchanges (initial effective sizes), the transition of gene correlations (instantaneous effective sizes), and the steady-state (asymptotic effective size). Results indicate that systems of mating that incorporate more than one male mate per female increase all effective sizes above those expected from polygyny and monogamy. Instantaneous and asymptotic sizes can be expressed relative to the fixation indices. The parameters presented herein can be utilized in models of effective sizes for the study of evolutionary biology and conservation genetics. PMID- 7982569 TI - Gene and allelic genealogies at a gametophytic self-incompatibility locus. AB - The properties of gene and allelic genealogies at a gametophytic self incompatibility locus in plants have been investigated analytically and checked against extensive numerical simulations. It is found that, as with overdominant loci, there are two genealogical processes with markedly different time scales. First, functionally distinct allelic lines diverge on an extremely long time scale which is inversely related to the mutation rate to new alleles. These alleles show a genealogical structure which is similar, after an appropriate rescaling of time, to that described by the coalescent process for genes at a neutral locus. Second, gene copies sampled within the same functional allelic line show genealogical relationships similar to neutral gene genealogies but on a much shorter time scale, which is on the same order of magnitude as the harmonic mean of the number of gene copies within an allelic line. These results are discussed in relation to data showing trans-specific polymorphisms for alleles at the gametophytic self-incompatibility locus in the Solanaceae. It is shown that population sizes on the order of 4 x 10(5) and a mutation rate per locus per generation as high as 10(-6) could account for estimated allelic divergence times in this family. PMID- 7982570 TI - Hitoshi Kihara, Japan's pioneer geneticist. PMID- 7982571 TI - Roles of ruvA, ruvC and recG gene functions in normal and DNA damage-inducible replication of the Escherichia coli chromosome. AB - Induction of the SOS response in Escherichia coli activates normally repressed DNA replication which is termed inducible stable DNA replication (iSDR). We previously demonstrated that initiation of iSDR requires the products of genes, such as recA, recB and recC, that are involved in the early stages of homologous recombination. By measuring the copy number increase of the origin (oriM1) region on the chromosome, we show, in this study, that initiation of iSDR is stimulated by mutations in the ruvA, ruvC and recG genes which are involved in the late stages of homologous recombination. Continuation of iSDR, on the other hand, is inhibited by these mutations. The results suggest that Holliday recombination intermediates, left on the chromosome due to abortive recombination, arrest replication fork movement. Low levels of iSDR and sfiA (sulA) gene expression were also observed in exponentially growing ruvA, ruvC and recG mutants, suggesting that the SOS response is chronically induced in these mutants. We propose that replication forks are arrested in these mutants, albeit at a low frequency, even under the normal (uninduced) conditions. PMID- 7982572 TI - Microbial evolution in a simple unstructured environment: genetic differentiation in Escherichia coli. AB - Populations of Escherichia coli initiated with a single clone and maintained for long periods in glucose-limited continuous culture, become polymorphic. In one population, three clones were isolated and by means of reconstruction experiments were shown to be maintained in stable polymorphism, although they exhibited substantial differences in maximum specific growth rates and in glucose uptake kinetics. Analysis of these three clones revealed that their stable coexistence could be explained by differential patterns of the secretion and uptake of two alternative metabolites acetate and glycerol. Regulatory (constitutive and null) mutations in acetyl-coenzyme A synthetase accounted for different patterns of acetate secretion and uptake seen. Altered patterns in glycerol uptake are most likely explained by mutations which result in quantitative differences in the induction of the glycerol regulon and/or structural changes in glycerol kinase that reduce allosteric inhibition by effector molecules associated with glycolysis. The evolution of resource partitioning, and consequent polymorphisms which arise may illustrate incipient processes of speciation in asexual organisms. PMID- 7982573 TI - Construction of chromosomal rearrangements in Salmonella by transduction: inversions of non-permissive segments are not lethal. AB - Homologous sequences placed in inverse order at particular separated sites in the bacterial chromosome (termed "permissive") can recombine to form an inversion of the intervening chromosome segment. When the same repeated sequences flank other chromosome segments ("non-permissive"), recombination occurs but the expected inversion rearrangement is not found among the products. The failure to recover inversions of non-permissive chromosomal segments could be due to lethal effects of the final rearrangement. Alternatively, local chromosomal features might pose barriers to reciprocal exchanges between sequences at particular sites and could thereby prevent formation of inversions of the region between such sites. To distinguish between these two possibilities, we have constructed inversions of two non-permissive intervals by means of phage P22-mediated transduction crosses. These crosses generate inversions by simultaneous incorporation of two transduced fragments, each with a sequence that forms one join-point of the final inversion. We constructed inversions of the non-permissive intervals trp ('34) to his ('42) and his ('42) to cysA ('50). Strains with the constructed inversions are viable and grow normally. These results show that our previous failure to detect formation of these inversions by recombination between chromosomal sequences was not due to lethal effects of the final rearrangement. We infer that the "non permissive" character of some chromosomal segments reflects the inability of the recombination system to perform the needed exchanges between inverse order sequences at particular sites. Apparently these mechanistic problems were circumvented by the transductional method used here to direct inversion formation. PMID- 7982574 TI - Saccharomyces cerevisiae RAD52 alleles temperature-sensitive for the repair of DNA double-strand breaks. AB - We have screened for mutations of the Saccharomyces cerevisiae RAD52 gene which confer a temperature-sensitive (ts) phenotype with respect to either the repair of DNA lesions caused by methyl methanesulfonate (MMS) or the recombination of an intrachromosomal recombination reporter. We were readily able to isolate alleles ts for the repair of lesions caused by MMS but were unable to find alleles with a severe ts deficiency in intrachromosomal recombination. We extensively characterized four strains conferring ts growth on MMS agar. These strains also exhibit ts survival when exposed to gamma-radiation or when the HO endonuclease is constitutively expressed. Although none of the four alleles confers a severe ts defect in intrachromosomal recombination, two confer significant defects in tests of mitotic, interchromosomal recombination carried out in diploid strains. The mutant diploids sporulate, but the two strains with defects in interchromosomal recombination have reduced spore viability. Meiotic recombination is not depressed in the two diploids with reduced spore viability. Thus, in the two strains with reduced spore viability, defects in mitotic and meiotic recombination do not correlate. Sequence analysis revealed that in three of the four ts alleles the causative mutations are in the first one-third of the open reading frame while the fourth is in the C-terminal third. PMID- 7982575 TI - Characterization of mutations that suppress the temperature-sensitive growth of the hpr1 delta mutant of Saccharomyces cerevisiae. AB - The hpr1 delta 3 mutant of Saccharomyces cerevisiae is temperature-sensitive for growth at 37 degrees and has a 1000-fold increase in deletion of tandem direct repeats. The hyperrecombination phenotype, measured by deletion of a leu2 direct repeat, is partially dependent on the RAD1 and RAD52 gene products, but mutations in these RAD genes do not suppress the temperature-sensitive growth phenotype. Extragenic suppressors of the temperature-sensitive growth have been isolated and characterized. The 14 soh (suppressor of hpr1) mutants recovered represent eight complementation groups, with both dominant and recessive soh alleles. Some of the soh mutants suppress hpr1 hyperrecombination and are distinct from the rad mutants that suppress hpr1 hyperrecombination. Comparisons between the SOH genes and the RAD genes are presented as well as the requirement of RAD genes for the Soh phenotypes. Double soh mutants have been analyzed and reveal three classes of interactions: epistatic suppression of hpr1 hyperrecombination, synergistic suppression of hpr1 hyperrecombination and synthetic lethality. The SOH1 gene has been cloned and sequenced. The null allele is 10-fold increased for recombination as measured by deletion of a leu2 direct repeat. PMID- 7982576 TI - High-copy suppression of glucose transport defects by HXT4 and regulatory elements in the promoters of the HXT genes in Saccharomyces cerevisiae. AB - HXT4, a new member of the hexose transporter (HXT) family in Saccharomyces cerevisiae was identified by its ability to suppress the snf3 mutation in multicopy. Multicopy HXT4 increases both high and low affinity glucose transport in snf3 strains and increases low and high transport in wild-type strains. Characterization of HXT4 led to the discovery of a new class of multicopy suppressors of glucose transport defects: regulatory elements in the promoters of the HXT genes. We have designated these sequences DDSEs (DNA sequence dependent suppressing element). Multicopy HXT4 and DDSEs in the HXT1, HXT2, HXT3 and HXT4 promoters were found to restore growth to snf3 and grr1 strains on low glucose media. The DDSE in the HXT4 promoter was refined to a 340-bp sequence 450 bp upstream of the HXT4 translational start. This region was found to contain an 183 amino acid open reading frame. Extensive analysis indicates that the DNA sequence itself and not the encoded protein is responsible for suppression. The promoters of SNF3 and of other glycolytic genes examined did not suppress snf3 in multicopy. Suppression of snf3 by DDSE is dependent on the presence of either HXT2 or HXT3. PMID- 7982577 TI - Site-directed mutations altering the CAAX box of Ste18, the yeast pheromone response pathway G gamma subunit. AB - The STE18 gene encodes the gamma subunit of the G protein which functions in the Saccharomyces cerevisiae pheromone-response pathway. The STE18 gene product undergoes a post-translational processing at the carboxyl terminus directed by the CCAAX box motif CCTLM110. A variety of site-directed mutations of this sequence have been constructed to test the role of this motif on Ste18 function. Mutations which change or eliminate the cysteine at position 107 abolish Ste18 dependent mating, and thus the cysteine (C107) is essential for Ste18 function. However, inactivation of the prenyltransferase by disruption of DPR1 has only a minor effect on Ste18-dependent mating. Mutation of cysteine 106 to serine significantly reduces but does not eliminate Ste18 function. Deletion of the C terminal TLM sequence or modification of the ultimate methionine to lysine, arginine or leucine, all changes which do not affect the CAAX box cysteines, have only minor effects on Ste18-dependent mating. Intriguingly, these latter mutations dramatically compromise Ste18 function in cells which are deleted for Gpa1, the alpha subunit of the G protein. In addition, overexpression of these mutant versions of STE18 causes a dominant negative phenotype and inhibits the constitutive mating response generated by GPA1 deletion in cells which contain a functional STE18 gene. These results suggest that the C terminus of Ste18 and the Gpa1 protein have overlapping roles in some aspect of yeast G protein function such as membrane targeting. PMID- 7982578 TI - Genetic analysis of Dictyostelium slug phototaxis mutants. AB - Mapping and complementation analysis with 17 phototaxis mutations has established 11 complementation groups phoA-phoK distributed over six linkage groups. Statistical calculations from the complementation data yielded 17 as the maximum likelihood estimate of the number of pho genes assuming all loci are equally mutable. Most of the phototaxis mutants were found to exhibit bimodal phototaxis and all were found to be impaired in positive thermotaxis supporting convergence of the photosensory and thermosensory pathways. The thermotaxis mutant HPF228 was unaltered in phototaxis suggesting that the mutation in this strain affects a gene product whose site of action is before the convergence of the two pathways. Other phenotypes such as multiple tip formation by aggregates, stumpy fruiting bodies with short or absent stalks and short migration were associated with some pho alleles suggesting multiple biological roles for some gene products important in phototransduction. PMID- 7982579 TI - The Caenorhabditis elegans locus lin-15, a negative regulator of a tyrosine kinase signaling pathway, encodes two different proteins. AB - The Caenorhabditis elegans locus lin-15 negatively regulates an intercellular signaling process that induces formation of the hermaphrodite vulva. The lin-15 locus controls two separate genetic activities. Mutants that lack both activities have multiple, ectopic pseudo-vulvae resulting from the overproduction of vulval cells, whereas mutants defective in only one lin-15 activity appear wild-type. lin-15 acts non-cell-autonomously to prevent the activation of a receptor tyrosine kinase/ras signaling pathway. We report here the molecular characterization of the lin-15 locus. The two lin-15 activities are encoded by contiguous genomic regions and by two distinct, non-overlapping transcripts that may be processed from a single mRNA precursor by trans-splicing. Based on the DNA sequence, the 719- and 1,440-amino acid lin-15 proteins are not similar to each other or to known proteins. lin-15 multivulva mutants, which are defective in both lin-15 activities, contain deletions and insertions that affect the lin-15 genomic region. PMID- 7982581 TI - Ethics of ApoE testing: straw polls reveal doubts. PMID- 7982580 TI - The dpy-30 gene encodes an essential component of the Caenorhabditis elegans dosage compensation machinery. AB - The need to regulate X chromosome expression in Caenorhabditis elegans arises as a consequence of the primary sex-determining signal, the X/A ratio (the ratio of X chromosomes to sets of autosomes), which directs 1X@A animals to develop as males and 2X/2A animals to develop as hermaphrodites. C. elegans possesses a dosage compensation mechanism that equalizes X chromosome expression between the two sexes despite their disparity in X chromosome dosage. Previous genetic analysis led to the identification of four autosomal genes, dpy-21, dpy-26, dpy 27 and dpy-28, whose products are essential in XX animals for proper dosage compensation, but not for sex determination. We report the identification and characterization of dpy-30, an essential component of the dosage compensation machinery. Putative null mutations in dpy-30 disrupt dosage compensation and cause a severe maternal-effect, XX-specific lethality. Rare survivors of the dpy 30 lethality are dumpy and express their X-linked genes at higher than wild-type levels. These dpy-30 mutant phenotypes superficially resemble those caused by mutations in dpy-26, dpy-27 and dpy-28; however, detailed phenotypic analysis reveals important differences that distinguish dpy-30 from these genes. In contrast to the XX-specific lethality caused by mutations in the other dpy genes, the XX-specific lethality caused by dpy-30 mutations is completely penetrant and temperature sensitive. In addition, unlike the other genes, dpy-30 is required for the normal development of XO animals. Although dpy-30 mutations do not significantly affect the viability of XO animals, they do cause them to be developmentally delayed and to possess numerous morphological and behavioral abnormalities. Finally, dpy-30 mutations can dramatically influence the choice of sexual fate in animals with an ambiguous sexual identity, despite having no apparent effect on the sexual phenotype of otherwise wild-type animals. Paradoxically, depending on the genetic background, dpy-30 mutations cause either masculinization or feminization, thus revealing the complex regulatory relationship between the sex determination and dosage compensation processes. The novel phenotypes caused by dpy-30 mutations suggest that in addition to acting in the dosage compensation process, dpy-30 may play a more general role in the development of both XX and XO animals. PMID- 7982582 TI - Extended hormone replacement: who should get it, and for how long? AB - Hormone replacement therapy (HRT) after menopause may prevent cardiovascular disease and osteoporosis, chronic diseases that become increasingly important with age. For cardiovascular disease, this protection may be greatest in women with more risk factors, including age. Data suggest that HRT may mitigate bone loss in women 15 years or more past menopause, but reports are inconclusive regarding how HRT initiated after substantial bone is lost affects fracture incidence. The most troubling question is the possible association between HRT and breast cancer. Both clinician and patient must be aware of the potential for hormone-related symptoms following the initiation of HRT. Most symptoms fade in the first few months, but older women may be less willing to accept these problems unless they are provided a clear rationale for therapy. PMID- 7982583 TI - Using antiviral agents to control outbreaks of influenza A infection. AB - Risk of influenza mortality is high among older Americans and especially so among those residing in nursing homes. Current recommendations call for annual vaccination of all nursing home residents and staff against type A influenza, but outbreaks can and do occur even in homes with high vaccination rates. If an outbreak occurs, all residents--whether ill or not--should receive an antiviral drug, and prophylaxis should be initiated regardless of residents' vaccination status. The antiviral agents rimantadine and amantadine are both effective for prophylaxis and treatment of type A influenza, but rimantadine appears to cause fewer CNS side effects. PMID- 7982584 TI - Making the diagnosis when the patient has 'blue toes'. AB - Painful "blue toes" describes a physical sign whose meaning may be discovered through a carefully taken history, physical, and laboratory evaluation. Accurate diagnosis is important, because therapy for one specific condition may be contraindicated for another. When embolism is suspected, ultrasound examination of the heart, aorta, and periphery may be useful prior to angiography in order to avoid exacerbation of cholesterol crystal embolization. Transesophageal echocardiography or MRI may be needed to exclude a thoracic aortic source. The differential diagnosis can be divided into three categories: emboli from the cardiac and arterial system, acquired hypercoagulability disorders, and syndromes that lead to peripheral vascular pathology. A clinical approach to the evaluation of patients is presented, with case reports. PMID- 7982585 TI - Tough calls: making ethical decisions in the care of older patients. AB - Medicine is a moral endeavor concerned with the good of treating those who are ill. An ethical decision is the justifiable response to a "should" question, with consequences of good or harm. Three conditions are necessary for a patient to share in making an ethical decision: competence, voluntariness, and knowledge related to the condition of illness. In cases of incapacity, either the standard of substitute judgment or of best interest may be applied. Ideally, an ethical decision is a shared decision between providers and patients. In cases of conflict, continuing communication and dialogue are morally superior to the use of power. PMID- 7982586 TI - Excuses, excuses: the research paradox. PMID- 7982587 TI - Lymph nodes and cancer. A review. PMID- 7982588 TI - The lymphatic system and cancer. Mechanisms and clinical management. 28th annual San Francisco Cancer Symposium. March 6-7, 1993. Proceedings. PMID- 7982589 TI - Management of hilar and mediastinal lymph nodes with radiation therapy in the treatment of lung cancer. PMID- 7982590 TI - Tumor microenvironment: paracrine and autocrine growth mechanisms and metastasis to specific sites. PMID- 7982591 TI - Upper gastrointestinal cancers: rationale, results, and techniques of treatment. PMID- 7982592 TI - Lower gastrointestinal cancers: rationale, results, and techniques of treatment. PMID- 7982593 TI - Renal, renal pelvis and ureteral tumors: should retroperitoneal nodes be treated? AB - Transitional cell carcinoma of the upper urinary tract is rare. Tumors arising in the renal pelvis and calyces should be treated with nephroureterectomy, irrespective of stage and grade. Low-grade, low-stage ureteral tumors may be treated with conservative resection in order to preserve renal function. High grade, more advanced ureteral tumors should be treated with nephroureterectomy because of the high incidence of recurrence associated with local resection. The role of lymphadenectomy for upper tract transitional cell carcinoma has never been evaluated; however, it is recommended for better staging of the disease and for recommendations regarding adjuvant therapy. Adjuvant radiation therapy to sterilize microscopic residual disease and prevent local recurrence is logical. The role of adjuvant chemotherapy is under investigation. PMID- 7982594 TI - Prostate cancer: defining the roles of elective and therapeutic nodal irradiation. PMID- 7982595 TI - Nonseminoma testicular cancer: surveillance versus treatment. PMID- 7982596 TI - Early stage testicular seminoma: the role of radiation therapy following orchiectomy. PMID- 7982597 TI - Can patients with regional metastases from carcinoma of the endometrium be cured with radiation therapy? PMID- 7982598 TI - Management of lymph node metastasis in carcinoma of the cervix. PMID- 7982599 TI - Vulvar carcinoma: radiotherapy or surgery for the lymphatics? PMID- 7982600 TI - Management of the regional lymph nodes in malignant melanoma: surgery, radiotherapy or observation. PMID- 7982601 TI - Lymphoscintigraphy: importance to cancer detection and radiation treatment planning. PMID- 7982602 TI - Effects of ionizing radiation on lymph nodes. A review. PMID- 7982603 TI - Radiobiology of subclinical disease. PMID- 7982604 TI - Treatment of the neck in head and neck mucosal squamous cell carcinoma: what our experience teaches. PMID- 7982605 TI - Neck node metastases from unknown primary. Controversies in management. PMID- 7982606 TI - Controversies in the management of the lymphatics in breast cancer. PMID- 7982607 TI - The role of surgery in N1 and N2 lung cancer. PMID- 7982608 TI - [Clinical, immunologic and cytochemical parameters in workers of asbestos concrete industry]. PMID- 7982609 TI - [Evaluation of effectiveness of experimental device "Elf" in development of local non-bacterial zone]. PMID- 7982610 TI - [Characteristics of development of hygienic environmental factors in the milk processing industry]. AB - The main environmental unfavourable factors at dairy factories are noise, dust, microflora, microclimatic discomfort, insufficient lighting. Methodological recommendations were elaborated for improvement of working conditions to lower worker's morbidity. PMID- 7982611 TI - [Effect of exogenic sulphur-containing chemicals on women (Review)]. PMID- 7982612 TI - [Comparative evaluation of radiation protective efficiency of regimens with various content of calcium, potassium and iron]. AB - Calcium deficit in ration of rats considerable reduced radioprotective potential of animals. The enrichment of ration for calcium, potassium, and iron improved radioprotection by changing velocity of accumulation and excretion of cesium. PMID- 7982613 TI - [Hygienic significance of vitamin supplementation for women-employees of poultry factories]. AB - Vitaminization of female workers of poultry factory during 3 years promoted normalization of vitamin metabolism, lowering of toxic and allergic effect of chemical substances and morbidity. Hygienic recommendations based on the results of investigation were given. PMID- 7982614 TI - [Hygienic evaluation of hyposensitivity of egg-shell powder in the cosmetics]. AB - Egg-shell powder was added to cosmetics in quantity up to 10%. Such cosmetics did not irritate and sensitize the skin, and had a positive influence on allergologic status of animals. PMID- 7982615 TI - [Hygienic aspects of standardization of motor activity in adolescents during leisure time]. PMID- 7982616 TI - [Comprehensive hygienic evaluation of nutritional status in adolescents in the European North]. AB - Energy expenditures, real nutrition, intellectual and physical capacity for work, vitamin sufficiency and morbidity of pupils at professional technical schools of Republic of Komi were studied. Hygienic recommendations on improvement of pupils' nutrition were developed. PMID- 7982617 TI - [Economic evaluation of damages to the health of the population exposed to environmental pollution of Revda]. PMID- 7982618 TI - [Prenatal effect of formaldehyde on offspring development]. PMID- 7982619 TI - [Medical and preventive significance of accident card for dangerous cargo]. PMID- 7982620 TI - [Staphylococcal microflora of the skin]. PMID- 7982621 TI - [Distribution of samples by density of contamination in various facilities]. PMID- 7982622 TI - [Methods of studying of hygienic safety in using of every day ozonizers]. PMID- 7982623 TI - [Methods of choosing the indices for assessment of hygienic monitoring of water reservoirs]. AB - Methodology for choice of priority indices of water pollution assessment was developed. Examples of calculation of indices for some of industrial sewage were given. PMID- 7982624 TI - Free radical formation by ansamycin benzoquinone in human breast tumor cells: implications for cytotoxicity and resistance. AB - The benzoquinonoid ansamycin antibiotics, geldanamycin and herbimycin A, are potent cytotoxins against tumor cells in vitro. We have examined the mechanism of their in vitro cytotoxicity against human breast adenocarcinoma (MCF-7) cells and we have found that multidrug-resistant MCF-7/ADRR cells that exhibit the MDR phenotype and the overexpression of P-170-glycoprotein, were cross-resistant to geldanamycin and herbimycin A. Verapamil, which binds competitively with P-170 glycoprotein, enhanced geldanamycin cytotoxicity 12-fold only in resistant cells, suggesting that geldanamycin may interact with the drug efflux protein. Geldanamycin and herbimycin A, like adriamycin, were reductively activated by the NADPH-cytochrome P450-reductase and formed reactive .OH. The formation of .OH was significantly lower in resistant cells. In contrast to adriamycin, the formation of .OH was unaffected by the addition of DNA, indicating that a DNA-complexed drug was redoxactive and may, therefore, may be more effective in killing tumor cells at the DNA level. These observations indicate that both the decreased free radical formation and interactions with P170 glycoprotein may be important in geldanamycin and herbimycin A resistance in multidrug resistant human breast tumor cells. PMID- 7982625 TI - Structural basis of potent antiperoxidation activity of the triterpene celastrol in mitochondria: effect of negative membrane surface charge on lipid peroxidation. AB - The structural basis of the potent inhibitory effect of the triterpene celastrol on lipid peroxidation of rat liver mitochondria initiated by adenosine 5' diphosphate (ADP) and Fe2+ was studied in comparison with the effects of its analogs, pristimerin and acetylcelastrol. The dienone-phenol moiety and the anionic carboxyl group of celastrol were concluded to be important for their antiperoxidative action: The former moiety directly scavenges radicals and the latter donates the membrane with a negative surface charge, making it more resistant to peroxidation. Celastrol is suggested to inhibit the peroxidation of the outer and inner mitochondrial membrane by direct radical scavenging, and also to prevent the attack of oxygen radicals on the inner membrane by increasing its negative surface charge. PMID- 7982626 TI - Stability of Escherichia coli sodA mRNA and identification of the transcriptional start site(s) under different environmental and oxidative stresses. AB - Manganese-containing superoxide dismutase (MnSOD-sodA) in Escherichia coli (E. coli) is regulated at the transcriptional level as observed in studies using both operon and gene fusions. In this paper we examine the regulation of sodA gene at the level of mRNA. We examine the effects of several aerobic inducing conditions (i.e., nalidixic acid, paraquat, or 2,2'-dipyridyl) on mRNA stability, transcription initiation, and translation. The half-life of sodA mRNA was found to be approximately 3-4 min, showing no differences in mRNA stability between induced and uninduced cells. We also found, by reverse transcriptase, that the second putative promoter is not functional under normal or stress conditions, and the amount of mRNA was found to be proportional to active MnSOD. Thus, these results indicate that under oxidative stress/inducing conditions, the increase in aerobic transcription of sodA occurs from only one transcription start site without affecting the stability of sodA mRNA. In addition, the 1:1 ratio found between increases in sodA mRNA and active MnSOD suggests that no translational regulation occurs aerobically. PMID- 7982627 TI - Determination of the rate of superoxide generation from biological systems by spin trapping: use of rapid oxygen depletion to measure the decay rate of spin adducts. AB - A method was developed to measure the superoxide generation rate from biological systems using the spin trapping method. Kinetic treatment of the decay rate of the superoxide adduct of 5,5-dimethylpyrroline N-oxide (DMPO) revealed that the EPR signal intensity of the system is proportional to the superoxide generation rate. Rapid depletion of oxygen in the sample was utilized to terminate superoxide generation so that the decay rate of the DMPO superoxide adduct (DMPO OOH) could be determined. For this decay measurement, a controlled atmosphere EPR cavity was developed and was used with an open-air sample cell. Superoxide generation rates determined with this method for stimulated neutrophils and for the hypoxanthine-xanthine oxidase system were comparable to those obtained with the cytochrome c reduction method. This method is specifically applicable to the system in which dissolved oxygen supplied from the gas phase is utilized as a source of superoxide. PMID- 7982628 TI - Oxidative stress in the development of human ischemic hepatitis during circulatory shock. AB - An increasing number of studies support the involvement of free radical-mediated oxidative reactions in the pathogenesis of tissue injury following ischemia reperfusion. In particular, a condition of oxidative stress is evident in patients with circulatory shock, a disease process often complicated by progressive organ failure sustained by inflammatory reactions. In all shock patients without signs of organ failure, a consistent increase of intermediate and final products of lipid peroxidation (lipid peroxides and aldehydes respectively) was observed. Impairment of the redox equilibrium in the tissues of these patients was confirmed by a significant reduction of glutathione and vitamin E hematic concentrations. Moreover, a selective increase of plasma aldehyde-protein adducts, actual proof of oxidative damage of macromolecules, is only present in the shock patients who, in addition, show hepatic cytolysis (ischemic hepatitis) as estimated by plasma levels of LDH5 isoenzyme. Aldehyde adducts well mark the progression of the disease towards multiple organ failure. Finally, the good statistical correlation between aldehyde-modified proteins and LDH5, as well as their distinct behaviour in control and ischemic hepatitis, support the involvement of oxidative damage in the expression and worsening of circulatory shock. PMID- 7982629 TI - Importance of Se-glutathione peroxidase, catalase, and Cu/Zn-SOD for cell survival against oxidative stress. AB - Eukaryotic cells have to constantly cope with highly reactive oxygen-derived free radicals. Their defense against these free radicals is achieved by natural antioxidant molecules but also by antioxidant enzymes. In this paper, we review some of the data comparing the efficiency of three different antioxidant enzymes: Cu/Zn-superoxide dismutase (Cu/Zn-SOD), catalase, and selenium-glutathione peroxidase. We perform our comparison on one experimental model (human fibroblasts) where the activities of these three antioxidant enzymes have been modulated inside the cells, and the repercussion of these changes was investigated in different conditions. We also focus our attention on the protecting role of selenium-glutathione peroxidase, because this enzyme is very rarely studied due to the difficulties linked to its biochemical properties. These studies evidenced that all three antioxidant enzymes give protection for the cells. They show a high efficiency for selenium-glutathione peroxidase and emphasize the fact that each enzyme has a specific as well as an irreplaceable function. They are all necessary for the survival of the cell even in normal conditions. In addition, these three enzymes act in a cooperative or synergistic way to ensure a global cell protection. However, optimal protection is achieved only when an appropriate balance between the activities of these enzymes is maintained. Interpretation of the deleterious effects of free radicals has to be analyzed not only as a function of the amount of free radicals produced but also relative to the efficiency and to the activities of these enzymatic and chemical antioxidant systems. The threshold of protection can indeed vary dramatically as a function of the level of activity of these enzymes. PMID- 7982630 TI - Superoxide dismutase, aging, and degenerative disease. AB - Over 15 years of research on correlations between superoxide dismutase (SOD) activity and aging or life span have failed to provide a consistent picture of the role of SOD in aging. While genetic manipulations that increase CuZn-SOD activity have only a slight, if any, effect on maximum life span in several species, they do increase resistance to oxidative stress. However, increasing both CuZn-SOD and catalase does significantly increase maximum life span. Decreased SOD expression in a variety of species increases their vulnerability to oxidative stress, and in the case of genetically altered CuZn-SOD, leads to premature death of motor neurons in humans. Little is known about the regulation of expression of SOD and other antioxidant defense enzymes in eukaryotes. The research summarized below collectively suggest that SOD plays an important role in longevity and degenerative disease, but much remains to be learned before manipulation of SOD expression can be considered for effective intervention in either process. PMID- 7982631 TI - Photochemiluminescent detection of antiradical activity: II. Testing of nonenzymic water-soluble antioxidants. AB - A method for testing and quantification of nonenzymic antioxidants, such as ascorbic acid and uric acid, and of polycomponent systems, e.g., blood plasma, is described. This method is based on a photo-induced, chemiluminescence accompanied, and antioxidant-inhibitable autoxidation of luminol. The sensitivity of the assay lies in a region of nanomolar quantities of substances. The interassay variability of the method is lower than 5%, the intraassay variability is 2%. The mean values of an integral antioxidant capacity (AC) of human blood plasma, measured with this method as a duration of the chemiluminescence inhibition, were between 10 and 20 arbitrary Units (10 arb.U. = 1 min) per 1 microliter, and showed the age-dependent patterns with maximal values (+/- SD) with newborns (n = 7): 20.8 +/- 4.1 arb.U. and aged persons (46 +/- 9.4 years old, n = 16): 15.4 +/- 5.2 arb.U., and minimal with children (7.3 +/- 3 years old, n = 10): 9.9 +/- 2.6 arb.U. AC of young people (28.7 +/- 6.5 years old, n = 22) was 12.1 +/- 2.7 arb.U. AC of six tested animal species was lower as that of humans, with maximal values with guinea pigs: 8.5 arb.U. (mean value) and spontaneously hypertensive rats: 8.6 arb.U. The lowest values were registered with minipigs: 1.4 arb.U. Mice (strain 17) showed 3.8, Lewis and Wistar rats accordingly 4.6 and 6.2 arb.U. PMID- 7982632 TI - Biphenyl compounds are hydroxyl radical scavengers: their effective inhibition for UV-induced mutation in Salmonella typhimurium TA102. AB - In our previous study, we found several hydroxylated biphenyl compounds have a great scavenging effect for hydroxyl radicals (.OH). In this study, to elucidate the relationship between generation of the .OH and photo-mutagenesis, six biphenyl compounds such as dehydrodieugenol, dehydrodivanillyl alcohol, dehydrodidihydroeugenol, dehydrodicreosol, magnolol and honokiol, respectively, were examined for their ability to inhibit UV-induced mutation in Salmonella typhimurium TA102. The relative mutagenic activities (RMA, %) indicated the mutation frequency of treated cells divided by the mutation frequency of control cells times 100%. The RMA (%) are as follows: 28 +/- 1, 31 +/- 1, 33 +/- 1, 41 +/ 2, 62 +/- 1, and 62 +/- 4 at concentrations of 5 micrograms per plate for dehydrodieugenol, dehydrodivanillyl alcohol, dehydrodidihydroeugenol, dehydrodicreosol, magnolol, and honokiol, respectively. These values indicate that low concentrations of these biphenyl compounds effectively suppress UV induced mutagenesis. Also, these compounds acted as effective antimutagens in a dose-dependent manner (0.00005-5 micrograms per plate). These compounds are effective .OH scavengers. Consequently, the results obtained above suggest that these compounds could inhibit against UV-induced mutations by scavenging of .OH generated by UV irradiation. The results also suggest that .OH are associated with UV-induced mutation in Salmonella typhimurium TA102. PMID- 7982633 TI - Myocardial bars and bridges and sudden death. AB - A congenital variant of the anatomical arrangement of the coronary arteries, that can be observed both angiographically and at autopsy, is the embedding of these vessels within a tunnel of the subepicardial myocardium. Both clinical and pathological claims and counterclaims have been made as to the functional consequences of this variation, the implication being that the contraction of the peri-vascular myocardium particularly at accentuated heart rates would cause occlusion of the blood flow within these arteries. The consensus is that this variant is only of significance when it occurs around a significant portion of a dominant left main coronary artery in which instances it may be the cause of sudden death during the course of strenuous exercise. PMID- 7982634 TI - Experimental evaluation of rigor mortis. VIII. Estimation of time since death by repeated measurements of the intensity of rigor mortis on rats. AB - The development of the intensity of rigor mortis was monitored in nine groups of rats. The measurements were initiated after 2, 4, 5, 6, 8, 12, 15, 24, and 48 h post mortem (p.m.) and lasted 5-9 h, which ideally should correspond to the usual procedure after the discovery of a corpse. The experiments were carried out at an ambient temperature of 24 degrees C. Measurements initiated early after death resulted in curves with a rising portion, a plateau, and a descending slope. Delaying the initial measurement translated into shorter rising portions, and curves initiated 8 h p.m. or later are comprised of a plateau and/or a downward slope only. Three different phases were observed suggesting simple rules that can help estimate the time since death: (1) if an increase in intensity was found, the initial measurements were conducted not later than 5 h p.m.; (2) if only a decrease in intensity was observed, the initial measurements were conducted not earlier than 7 h p.m.; and (3) at 24 h p.m., the resolution is complete, and no further changes in intensity should occur. Our results clearly demonstrate that repeated measurements of the intensity of rigor mortis allow a more accurate estimation of the time since death of the experimental animals than the single measurement method used earlier. A critical review of the literature on the estimation of time since death on the basis of objective measurements of the intensity of rigor mortis is also presented. PMID- 7982635 TI - Types of trauma in cases of homicide. AB - A group of 251 victims of homicide in the years 1978-1988 were examined to determine the causes of their injuries. It was found that 51.4% of homicide victims exhibited evidence of injuries due to blunt trauma, 31.9% were victims of sharp trauma and 29.5% suffered from strangulation. Less common were shootings (18.7%) and other traumata (4.0%). Males were most commonly victims of injuries caused by blunt (51.9%) and sharp (33.6%) trauma, possibly due to more frequent physical confrontations among men. Females also demonstrated injuries due to blunt trauma (50.8%), but strangulation was nearly equal (47.5%). Women were commonly murdered by the aggressor's bare hands within the setting of conflicts in relationships. In 36.7% of all cases, injuries were caused by a combination of aggressive traumas. Combined injuries were common in cases of strangulation (77.3%), blunt trauma (64.3%) and sharp trauma (46.9%), whereas shooting injuries were seldom combined (12.8%) because they were usually fatal alone. Female victims demonstrated combined fatal injuries more frequently than males, probably because conflicts in relationships can cause extreme emotional outbursts and thus lead to the use of multiple aggressive traumatisations. PMID- 7982636 TI - Analysis of the D1S80 locus by amplified fragment length polymorphism technique in the Chinese, Malays and Indians in Singapore. AB - The distributions of the D1S80 alleles and genotypes in the Chinese, Malays and Indians in Singapore were determined by amplified fragment length polymorphism (AMP-FLP) analysis. The distributions of the observed genotypes for the three races conformed to Hardy-Weinberg expectations. The system was applied to 19 families whose paternity had been established by restriction fragment length polymorphism (RFLP) analysis. In all cases, Mendelian inheritance of the alleles at the D1S80 locus could be demonstrated. D1S80 typing on DNA recovered by differential extraction of forensic specimens which included vaginal swabs, urethral swabs and seminal stains yielded consistent results. PMID- 7982637 TI - Individualization of fresh and stored human urine samples by PGM1- and Gc subtyping. AB - After 50- to 200-fold concentration by ultrafiltration, 56 fresh urine samples from healthy individuals (26 men, 30 women) and eight samples from corpses were subjected to isoelectrofocusing methods. All the urine samples tested could be correctly typed in both the phosphoglucomatase 1 (PGM1) and Gc system when compared to reference blood samples. The activity of urinary PGM1 revealed intraindividual and interindividual variations. To our knowledge this is the first report of PGM1 detection in urine. A systematic storage experiment over a period of 6 months was carried out at different temperatures (-20 degrees C, 4 degrees C, 20 degrees C); furthermore, aging of urine samples from 4 months to 4 years was investigated. The heterogeneous typing results were as follows. For Gc: after a storage period of 6 months positive results could be obtained in approximately 40% of those samples that were stored frozen (-20 degrees C) or in a refrigerator (4 degrees C). Some samples, however, showed negative analyses already after a 1 month storage period. At room temperature positive results could be achieved up to 3 months. Additional bands can appear in pherograms of urine samples stored at room temperature or in a refrigerator; they may cause misinterpretation, dependent on the original Gc-type. The maximum storage time compatible with successful Gc-typing was 1 year. For PGM1: this polymorphism could be regularly detected up to 1 week, and in some cases up to 1 month, in urine samples stored at 4 degrees C. The PGM1 activity gradually decreased; there were no additional or variant bands. PMID- 7982638 TI - Hepatic and extrahepatic hepatitis C virus replication in relation to response to interferon therapy. AB - Response to a 1-yr course of interferon-alpha 2b was assessed in 18 patients with chronic hepatitis C virus infection in relation to clinical, biochemical and histological parameters and to the presence or absence of hepatitis C virus RNA and the presumed replicative form of the virus (negative-strand hepatitis C virus RNA) in serum, liver and peripheral blood mononuclear cells. The findings were compared with those in seven untreated patients studied over the same period. At the start of the study, positive-strand hepatitis C virus RNA was found in sera of all 25 patients, in livers of 24 and in peripheral-blood mononuclear cells of 19 of 22 tested; negative strand was found in livers of 11 and in peripheral blood mononuclear cells of 15 of 22. Negative-strand hepatitis C virus RNA was not found in the serum of any patient at any stage. All of the five treated patients considered to show complete response during the study period cleared hepatic hepatitis C virus RNA, and four also became seronegative, but three had evidence suggestive of viral replication in their peripheral-blood mononuclear cells; two of these last patients subsequently relapsed. Loss of hepatic hepatitis C virus RNA was the only significant difference between these five and the seven partial and six nonresponders, but it is uncertain whether the observed changes were due specifically to interferon-induced modulation of virus expression because similar (apparently spontaneous) changes were seen in four of the untreated patients.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7982639 TI - Genotypic analysis of hepatitis C virus in American patients. AB - We examined hepatitis C virus genotypes in 98 American patients with chronic hepatitis C virus infection by means of two methods; restriction fragment length polymorphism analysis and line probe assay, which is based on type-specific sequence variations in the 5' untranslated region. Type 1 was present in 73 patients (74%), type 2 in 15 (15%), type 3 in 6 (6%) and type 4 in 1 (1%). Line probe assay further subdivided type 1 into 1a (n = 35) and type 1b (n = 37) and type 2 into type 2a (n = 6) and 2b (n = 9). Two patients (2%) had both restriction fragment length polymorphism and line probe assay evidence of dual infection (with types 1 and type 2) while another case had both type 1a and 1b by line probe assay. One patient was untypable by either technique. There was no correlation between infecting genotype and presumed cause, serum indexes of necroinflammatory activity, or age or sex of the patients studied or known duration of infection. Patients with type 2 hepatitis C virus had more severe liver disease histologically (p = 0.0027) compared with other genotypes but, paradoxically, had significantly lower levels of circulating hepatitis C virus RNA (12.1 +/- 12.8 x 10(5) genome equivalents/ml) than other types (36.4 +/- 44.8 x 10(5) genome equivalents/ml, p < 0.001). Response to interferon was less likely to be sustained in patients infected with type 1 than in those infected with other types (7% vs. 40%, p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7982640 TI - Prognostic factors for hepatocellular carcinoma in genetic hemochromatosis. AB - To identify factors that might be useful as prognostic indexes for the risk of hepatocellular carcinoma in Italian patients with genetic hemochromatosis, 152 homozygotes were studied prospectively for 1 to 229 mo. Factors that were considered in estimating the risk of developing hepatocellular carcinoma were age, sex, cirrhosis (Child class), HBsAg, antibodies to HBsAg, antibodies to HBcAg, hepatitis C antibodies, alcohol abuse and the amount of iron removed during therapeutic phlebotomy to produce iron depletion. At diagnosis, cirrhosis was present in 97 patients and absent in 55. During follow-up, hepatocellular carcinoma developed in 28 of the 97 patients with cirrhosis but in none of those without. Among patients with cirrhosis, the cumulative probability of being free of hepatocellular carcinoma at 10 yr was 70%. For patients with and without HBsAg the probabilities of being free of liver cancer at 10 yr were, respectively, 54% and 75%; for those with and without history of alcoholism, 58% and 78%; and for those younger and older than 55 yr, 90% and 54%. In patients with cirrhosis, multivariate analysis using proportional-hazards (Cox) regression found that the only factors contributing significantly to the estimation of a prognostic index were age, presence of HBsAg and alcohol abuse. Age over 55 yr increased the relative risk of hepatocellular carcinoma 13.3-fold (p < 0.001), the presence of HBsAg increased it 4.9-fold (p < 0.02) and alcohol abuse increased it 2.3-fold (p < 0.04).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7982641 TI - Portal and gastric mucosal hemodynamics in cirrhotic patients with portal hypertensive gastropathy. AB - Controversy exists as to the nature of gastric perfusion in portal-hypertensive gastropathy. To investigate portal hemodynamics and gastric mucosal perfusion in cirrhotic patients with and without portal-hypertensive gastropathy, we subjected 56 cirrhotic patients with portal hypertension to portal vein catheterization, pneumatic pressure sensor technique, duplex sonography and laser Doppler flowmetry. Thirteen patients had portal-hypertensive gastropathy: In 10 it was mild, and in 3 it was severe. The presence of portal-hypertensive gastropathy seemed to be independent of age, sex, cause of cirrhosis or grade of esophageal varices. Portal venous pressure, esophageal variceal pressure, portal venous flow and congestion index in patients with portal-hypertensive gastropathy were not significantly different from the values in those without portal-hypertensive gastropathy. However, portal-variceal pressure gradient (subtracting esophageal variceal pressure from portal venous pressure) (p < 0.01) and the incidence of palisading-type esophageal varices on portography (p < 0.05) was increased in patients with portal-hypertensive gastropathy significantly more than in those without portal-hypertensive gastropathy. In the fundus, gastric mucosal blood flow was significantly higher in patients with portal-hypertensive gastropathy than in those without portal-hypertensive gastropathy, whereas in the corpus and the antrum the values were not significantly different. We suggest that the mucosa of the upper stomach in patients with portal-hypertensive gastropathy is congestive and highly perfused. The pathogenesis of portal-hypertensive gastropathy may be related to both congestion and hyperemia in the upper stomach. PMID- 7982642 TI - Chlorpromazine-induced vanishing bile duct syndrome leading to biliary cirrhosis. AB - We describe a 33-yr-old pregnant woman in whom a primary biliary cirrhosis-like syndrome developed after 2 wk of chlorpromazine therapy. The clinical course was characterized by severe jaundice lasting 22 mo, intense pruritus, fever, steatorrhea, high alkaline phosphatase levels and hypercholesterolemia. Jaundice resolved with initiation of ursodeoxycholic acid therapy, but subclinical cholestasis and low-level inflammatory activity persisted and ultimately evolved into biliary cirrhosis. The pathological substrate of this severe and prolonged cholestatic reaction was found to be the vanishing bile duct syndrome with a marked transient pseudoxanthomatosis. PMID- 7982643 TI - Prevalence of chronic liver disease in the general population of northern Italy: the Dionysos Study. AB - Data on the prevalence of chronic liver disease, derived from selected series of hospitalized patients or from mortality registers, underestimate the prevalence of chronic liver disease. The Dionysos Study is a cohort study that investigated for the first time the prevalence of chronic liver disease in a general population. All the citizens of two towns in northern Italy, Campogalliano and Cormons, aged 12 to 65 yr were contacted by letter. From March 1991 through March 1993, 6,917 of a total of 10,150 citizens were enrolled (compliance, 69%). The standardized protocol for each enrollee included (a) a color-illustrated food questionnaire on dietary habits and alcohol intake; (b) a detailed medical history, including questions on risk factors for chronic liver disease; (c) a physical examination; and (d) blood tests for AST, ALT, gamma glutamyltranspeptidase, mean cell volume, platelet count and hepatitis B virus and hepatitis C virus markers. Signs suggestive of chronic liver disease were seen in 21.3% of the subjects, and who then underwent further liver function tests, upper abdominal ultrasonography and, when necessary, liver biopsy. Persistent signs of chronic liver disease were present in 17.5% of the subjects, including 1.1% with cirrhosis and 0.07% with hepatocellular carcinoma. The prevalence rates of hepatitis B virus and hepatitis C virus positivity (second generation enzyme-linked immunosorbent assay) were 1.3% and 3.2%, respectively. Alcohol abuse was the etiological agent in 23%.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7982644 TI - Mechanism of serum cholesterol reduction by oat bran. AB - Nine normolipidemic young men consumed a constant diet for 2 mo into which oat bran was incorporated during the second month so that we might test the hypotheses that oats lower serum cholesterol concentrations by decreasing bile acid and fat absorption and increasing bile acid synthesis. Bile acid kinetics were determined by measuring the 13C enrichment of serum cholic and chenodeoxycholic acids. Oat bran consumption decreased serum cholesterol levels (p < 0.01) and cholic acid pool size (p < 0.05). Deoxycholic acid pool size (p < 0.01) and the synthesis and fractional turnover rates of both primary bile acids (p < 0.05) increased. Total bile acid pool size did not change. Fecal excretion of total bile acids, the two secondary bile acids and fat increased significantly. The results demonstrate that oat bran lowers serum cholesterol levels in part by altering bile acid metabolism. In addition, the substantial increase in the proportion of the total bile acid pool that was deoxycholic acid is consistent with the hypothesis that oat bran also decreases cholesterol synthesis. PMID- 7982645 TI - Daily determination of individual serum bile acids allows early detection of hepatic allograft dysfunction. AB - Acute graft rejection is still a major cause of morbidity after orthotopic liver transplantation, and its diagnosis necessitates an invasive liver biopsy. Our aim has been to determine whether changes in individual serum bile acid levels after engraftment are sensitive, specific and reliable indicators of graft function and whether these changes can antedate other biochemical indicators of hepatic allograft rejection. Individual bile acids in 200 serum samples taken serially from eight adult liver transplant patients were measured. Patients with biopsy confirmed graft dysfunction due to rejection or nonrejection causes (n = 6 episodes) had significantly higher serum concentrations of glycocholate plus glycochenodeoxycholate and taurocholate/taurochenodeoxycholate ratios than did noncomplicated grafts (n = 3). These changes antedated any other conventional biochemical parameters by at least 48 hr and were 100% sensitive and specific. None of the conventional liver function tests could match this. Acute rejection episodes (n = 3) were then compared with nonrejection causes of graft dysfunction (n = 3). In acute rejection we noted a significant increase in the concentration of glycodeoxycholate plus deoxycholate and a significant decrease in the cholate/chenodeoxycholate ratio compared with that in nonrejection graft malfunction. Both of these changes antedated any other biochemical parameters by 24 hr. In conclusion, individual serum bile acid assays, after orthotopic liver transplantation, can detect graft dysfunction resulting from any cause at an earlier time than routine biochemical tests, and they are sensitive, specific and reliable for early detection of graft dysfunction. In addition, acute rejection can be distinguished from other causes of graft dysfunction. PMID- 7982646 TI - Phospholipid antibodies in alcoholic liver disease. AB - Alcoholic liver injury has been reported to be directed preferentially against the proteins of the cell membrane, sparing the phospholipids. However, antiphospholipid antibodies against certain cell membrane phospholipids are known to be associated with a variety of diseases. We undertook this investigation to determine whether antiphospholipid antibodies were present in the serum of patients with alcoholic liver disease. We investigated seventy long-term alcoholic patients (> 80 gm ethanol/day for > 1 yr) and 8 normal nonalcoholic controls by means of enzyme-linked immunosorbent assay to determine whether serum antibodies were generated against the following membrane phospholipids: phosphatidylserine, phosphatidylinositol, phosphatidylethanolamine, phosphatidylglycerol, diphosphatidylglycerol (cardiolipin) and phosphatidic acid. Group 1 comprised alcoholic patients with normal liver function (n = 13), group 2 comprised alcoholic patients with abnormal liver function (n = 16), group 3 comprised patients with alcoholic hepatitis or cirrhosis (n = 41) and group 4 comprised nonalcoholic controls (n = 8). The antibody prevalence was 15% in group 1, 31% in group 2, 81% in group 3 and 0% in group 4. In group 3, 20 of 41 patients had antibodies against several cell membrane phospholipids (i.e., phosphatidylethanolamine, phosphatidylserine, phosphatidylglycerol, phosphatidic acid, cardiolipin and phosphatidylinositol). The antiphosphatidylethanolamine isotype was IgA or IgM in 25 of 41 of these patients. Both IgA (p < 0.01) and IgM (p < 0.008) antiphosphatidylethanolamine correlated significantly with disease severity. Antiphospholipid antibodies in alcoholic patients seem to reflect disease progression and correlate significantly with disease severity. PMID- 7982647 TI - Effect of intrahepatic portal-systemic shunting on hepatic ammonia extraction in patients with cirrhosis. AB - Increased plasma ammonia levels in patients with advanced cirrhosis have been attributed to reduced conversion of enteric ammonia to urea by the diseased liver and to entry of enteric ammonia into systemic circulation by way of portal systemic shunts. Because single-pass extraction is high for portal venous ammonia, reduction of portal blood supply to hepatocytes may have detrimental effects on the hepatic extraction of ammonia. To assess how the development of intrahepatic portal-systemic shunts alters hepatic ammonia metabolism, we determined portal and hepatic venous ammonia levels along with measurements of intrahepatic portal-systemic shunts using 99mTc-macroaggregated albumin in 46 patients with portal hypertension. Hepatic venous ammonia levels in the groups of patients with idiopathic portal hypertension, Child class A cirrhosis and Child class B or C cirrhosis were 36 +/- 17, 75 +/- 26 and 93 +/- 52 micrograms/dl, respectively, in increasing order, and portal venous ammonia extraction rates as calculated with the equation (portal venous ammonia-hepatic venous ammonia)/portal venous ammonia x 100% were decreased in the same order (77% +/- 14%, 50% +/- 21%, 40% +/- 25%, respectively). Furthermore, we noted a significant negative correlation between the intrahepatic shunt indexes as calculated by counts per minute in lungs/counts per minute in lungs and liver x 100% and the ammonia extraction rates. It was noteworthy that among Child class C patients, the ammonia extraction rates were significantly lower in patients with high intrahepatic shunt indexes than in those with low shunt indexes. These results demonstrate a significant direct relationship between hepatic ammonia extraction rates and intrahepatic shunting in cirrhosis. PMID- 7982648 TI - Effect of distal splenorenal shunt on survival of patients with primary biliary cirrhosis. AB - Distal splenorenal shunt is known to effectively control bleeding from esophageal and gastric varices; however, the effect of this selective shunt on liver function is less well understood. We examined retrospectively the effect of distal splenorenal shunt on the survival of 19 patients with primary biliary cirrhosis subjected to surgery for bleeding varices over a 20-yr period and had been followed for at least 1 yr. Actual Kaplan-Meier survival curve was compared with predicted survival curve based on the Mayo Clinic model using clinical data collected at the time of surgery. The patients median length of follow-up was 65.9 mo. Ten of the 19 patients died or underwent orthotopic liver transplantation during the period of observation. The actual Kaplan-Meier and predicted Mayo Clinic model survival curves were similar and did not differ significantly. Survival was best in patients with good liver function (i.e., low Mayo risk scores). Distal splenorenal shunt, therefore, did not appear to have an adverse effect on the survival of patients with primary biliary cirrhosis. We conclude that variceal bleeding in primary biliary cirrhosis patients with good liver function should not be considered an indication for liver transplantation. Instead, if treatment with sclerotherapy or beta-blockers fails then distal splenorenal shunt will prevent recurrent bleeding in 90% of patients and leave them with an excellent prognosis. PMID- 7982649 TI - Serial recording of sensory evoked potentials: a noninvasive prognostic indicator in fulminant liver failure. AB - Sensory evoked potentials are markedly changed in patients with fulminant liver failure. It is unknown, however, whether serial recordings of sensory evoked potentials provide useful prognostic informations for patient management in fulminant liver failure. Ninety recordings of bilateral median nerve-stimulated short- and long-latency sensory evoked potentials were performed in 25 patients with fulminant liver failure (9 patients spontaneously recovered and survived, 8 patients were referred to emergency liver transplantation and 8 patients died). In all nine survivors the cortical long-latency sensory evoked potential N70 peak was constantly detectable between 74 and 162 ms. In all eight patients who subsequently underwent liver transplantation and in seven of eight patients who died, loss of the N70 peak developed during the course of fulminant liver failure. In 4 of 15 patients who were selected for liver transplantation according to the King's College criteria, the N70 peak was constantly detectable. All four transplantation candidates spontaneously recovered and survived without transplantation. In contrast, eight patients never did fulfill the criteria for liver transplantation. Five of them with constantly detectable N70 peak recovered spontaneously. However, in the remaining three patients loss of the N70 peak developed, and they ultimately died. The probability of correct outcome prediction by sensory evoked potentials is superior to that based on clinical criteria alone (0.96 vs. 0.72). Therefore serial recording of sensory evoked potentials may help identify (a) a subgroup among liver transplantation candidates who may spontaneously recover without transplantation and (b) a subgroup of patients with severe brain dysfunction who should undergo early liver transplantation even though they do not fulfill King's College criteria. PMID- 7982650 TI - Renal impairment after spontaneous bacterial peritonitis in cirrhosis: incidence, clinical course, predictive factors and prognosis. AB - Although spontaneous bacterial peritonitis is considered a precipitating factor of renal impairment in cirrhosis, no study specifically addressing this problem has been reported. This study was aimed at assessing the incidence, clinical course, predictive factors and prognosis of renal impairment in cirrhotic patients with peritonitis. Therefore, 252 consecutive episodes of spontaneous bacterial peritonitis in 197 patients were analyzed. Clinical and laboratory data obtained before and after diagnosis of peritonitis were considered as possible predictors of renal impairment and hospital mortality. Renal impairment occurred in 83 (33%) episodes, and in every instance it fulfilled the criteria of functional kidney failure. Renal impairment was progressive in 35 episodes, steady in 27 and transient in 21. Blood urea nitrogen and serum sodium concentration before peritonitis and band neutrophils count in blood at diagnosis were independent predictors for the development of renal impairment. Renal impairment was the strongest independent predictor of mortality during hospitalization. Other independent prognostic factors were blood urea nitrogen level before peritonitis, age, positive ascitic fluid culture and serum bilirubin level during infection. These results indicate that renal impairment is a frequent event in cirrhotic patients with spontaneous bacterial peritonitis that occurs mainly in patients with kidney failure before infection. Renal impairment is the most important predictor of hospital mortality in cirrhotic patients with spontaneous bacterial peritonitis. PMID- 7982651 TI - Propranolol plus isosorbide-5-mononitrate for portal hypertension in cirrhosis: long-term hemodynamic and renal effects. AB - The effect on kidney function, vasoactive systems and ascites outcome of long term treatment with propranolol plus isosorbide-5-mononitrate, a combined therapy proven more effective than propranolol alone in decreasing portal pressure in the cirrhotic patient, is unknown. Thirty cirrhotic patients who survived acute variceal bleeding and were treated with propranolol plus isosorbide-5-mononitrate were studied. Portal and systemic hemodynamics (n = 15), inulin clearance, free water clearance, plasma renin activity, aldosterone concentration and prostaglandin E2 excretion (n = 20) were measured before and after 3 mo of treatment. In addition, data on ascites outcome in the entire series after a mean follow-up of 9.6 mo were compared with those of 30 patients undergoing elective sclerotherapy and with those of 30 patients treated with propranolol alone matched for age, sex, presence of ascites, Child-Pugh class and mean follow-up length included in other randomized controlled trials. Combined therapy significantly decreased the hepatic venous pressure gradient and azygos blood flow. In addition, no changes in inulin clearance, free water clearance, plasma renin activity, aldosterone concentration and prostaglandin E2 excretion occurred, despite a mild decrease in mean arterial pressure. Moreover, no differences among the three groups of patients studied in ascites outcome were found. These results suggest that long-term treatment with propranolol plus isosorbide-5-mononitrate does not impair kidney function, vasoactive systems or ascites outcome in cirrhotic patients. PMID- 7982652 TI - Characteristics and regulation of bile salt synthesis and secretion by human hepatoma HepG2 cells. AB - Bile salt uptake, synthesis and secretion by the human hepatoma-derived cell line HepG2 were studied. The cells transported and secreted bile salts largely by means of passive mechanisms. The cells synthesized and secreted the normal human primary bile salts. The ratio of cholate to chenodeoxycholate was 1.5:1. The degree of conjugation, about 35%, was lower than normal, and the glycine-to taurine ratio was abnormal (4.5:1). This was not due to amino acid deficiency in the medium. Contrary to the report of others, little 3 alpha,7 alpha,12 alpha trihydroxy-5 beta-cholestan-26-oic acid was secreted. This was confirmed by gas chromatography-mass spectrometry. The total rate of synthesis was about 33% that of normal liver. The specific activity of bile salts synthesized from [3H]mevalonate was about 20 times higher than that of the cellular cholesterol derived from the same precursor. The regulation of bile salt synthesis by two compounds that could alter the precursor pool of cholesterol was studied. After a 24-hr incubation in serum-free medium, the compound 25(OH)cholesterol inhibited the rate of bile salt synthesis compared with control values, possibly by depleting the intracellular free cholesterol pool. Surprisingly, however, progesterone, which inhibits cholesterol esterification and should have expanded this pool, also inhibited bile salt synthesis under those conditions. The effect of these compounds on the level of mRNA for cholesterol 7 alpha-hydroxylase was also determined by Northern-blot analysis. The cholesterol 7 alpha-hydroxylase mRNA was 3.7 kb, similar to that in the rat. The incubation of cells in 25(OH)cholesterol or progesterone, as above, resulted in a decreased level of mRNA. The reduction was proportional to the reduction in bile salt synthesis, suggesting that these compounds act at a pretranslational level. Taken together, these results suggest that our particular subclone of HepG2 cells will be useful for studies of the regulation of bile salt synthesis, but not of transport, by human liver-derived tissue. PMID- 7982653 TI - The physiological position of the liver in the circulation is not a major determinant of its functional capacity. AB - The zonal patterns of gene expression in the liver of the rat are not affected by alteration of the afferent hepatic blood source. We investigated whether afferent hepatic blood source or flow rate affects the metabolic capacity of the liver. Using microsurgical techniques, we changed the afferent hepatic blood source to solely arterial blood, solely portal blood or solely caval blood. The transhepatic flow rate was four times higher in arterialized than in cavalized livers. Liver function was tested 2 wk after surgery. Three liver functions were tested (elimination of hepatic iminodiacetic acid from the liver and elimination of galactose and ammoniumbicarbonate from the circulation). Our results show that the afferent hepatic blood flow rate rather than the source of the afferent hepatic blood affects the elimination of the substrates tested. We found that at the physiological flow rate of approximately 15 ml/min and beyond, metabolic function does not depend on the flow of the afferent hepatic blood but that at lower flow rates the flow becomes a major determinant of the metabolic function of the liver. We conclude that the position of the liver within the circulation (i.e. between the gastrointestinal tract and the systemic circulation) is apparently not a prerequisite for adequate metabolic activity, at least for the substrates tested, provided that the liver is sufficiently perfused with blood. PMID- 7982654 TI - Effects of obesity on bile formation and biliary lipid secretion in the genetically obese JCR:LA-corpulent rat. AB - Obesity, a known risk factor in cholesterol gallstone disease, is a favorable factor in the formation of bile supersaturated with cholesterol. Previous studies have been indirect and limited to human beings. To better define the hepatic secretory defect, we directly measured bile secretion and bile salt kinetics in a genetically obese rat. Common bile duct cannulations and 24-hr bile collections were performed on 11 obese (homozygous for the cp gene) and 11 lean (heterozygous cp) female rats of the JCR:LA-cp strain. In absolute terms, obese rats had normal bile salt secretion rates, 28% larger bile salt pools and 45% greater bile salt synthesis than lean controls. Obese rats had twice the total liver DNA content of lean controls, indicating twice the liver cell number. In terms relative to liver cell number, bile salt synthesis per milligram DNA was no different in the obese rats and controls. Biliary secretion under basal conditions, when expressed per total DNA content, was significantly decreased in the obese rats. Bile salt and phospholipid secretion per milligram DNA were decreased 54% and 49%, respectively, whereas a lesser 31% reduction in cholesterol secretion resulted in an increased cholesterol saturation index. The bile salt secretion rate and bile flow per milligram DNA were both decreased by half in obese rats, a cholestatic state likely reflecting the accumulation of intracellular microvesicular fat and mitochondrial damage. The secretory defect in this model of obesity is therefore less bile salt and phospholipid in relation to the cholesterol secreted per liver cell. PMID- 7982655 TI - Role of polymorphonuclear leukocytes in galactosamine hepatitis: mechanism of adherence to hepatic endothelial cells. AB - To investigate the role of polymorphonuclear leukocytes in galactosamine-induced hepatic injury, we injected rats intraperitoneally with antiserum against rat polymorphonuclear leukocytes to deplete circulating neutrophils, then administered galactosamine plus lipopolysaccharide. Polymorphonuclear leukocytes in the hepatic sinusoids were increased after administration of galactosamine plus lipopolysaccharide, whereas pretreatment with the antiserum decreased the number of circulating leukocytes and reduced the mortality and the severity of hepatic injury. Serum collected 1 hr after galactosamine/lipopolysaccharide treatment enhanced in vitro polymorphonuclear leukocyte adherence to hepatic endothelial cells and induced leukocyte superoxide production. Intercellular adhesion molecule-1 expression on hepatic endothelial cells was also enhanced after stimulation with the serum. Polymorphonuclear leukocyte adhesion was partially inhibited by an antibody against tumor necrosis factor-alpha but not by superoxide dismutase. These results suggest that polymorphonuclear leukocytes play an important role in galactosamine-induced hepatic injury and that the accumulation and activation of leukocytes, as well as the enhanced expression of adhesion molecules on hepatic endothelial cells, can be induced by biologically active mediators such as tumor necrosis factor-alpha. In addition, prostaglandins E1 and E2 lessened the enhanced adherence of polymorphonuclear leukocytes and thus contributed to protection against hepatic injury. PMID- 7982656 TI - Potential role of bile duct collaterals in the recovery of the biliary obstruction: experimental study in rats using microcholangiography, histology, serology and magnetic resonance imaging. AB - Obstructive cholestasis induced in animals at the level of the lobar and common bile ducts is known to be reversible with time. This study was conducted not only to test the hypothesis that formation of bile duct collaterals is responsible for the recovery of biliary obstruction but also to assess the potential of hepatobiliary agent-enhanced magnetic resonance imaging for visualizing cholestasis. A total of 52 rats were divided into three groups with selective biliary obstruction, total biliary obstruction and sham surgery. We studied the evolution of cholestasis by correlating microcholangiographic, histological findings with the results of liver tests and hepatobiliary agent-enhanced magnetic resonance imaging. Lobar cholestasis undetected by liver tests but seen on magnetic resonance imaging as a difference between ligated and unligated lobes, occurred in 15 out of 20 rats subjected to selective biliary obstruction within 48 hr after ligation, and recovered later on as a result of the development of bile duct collaterals. Five rats failed to show local cholestasis as a result of the existence of interlobar accessory bile channels. All 18 total biliary obstruction-treated rats were cholestatic soon after ligation, as confirmed by high serum bilirubin and alkaline phosphatase levels and as documented by poor liver enhancement on magnetic resonance imaging. Cholestasis recovered within 4 wk with normalization of liver enhancement on magnetic resonance imaging as a result of the formation of bile duct collaterals (as demonstrated by microcholangiographic and histological study). Bile duct collateral formation is responsible for the recovery from obstructive cholestasis in rats. A similar mechanism might be present in conditions of bile duct obstruction without cholestasis. Hepatobiliary agent-enhanced magnetic resonance imaging is more sensitive than blood tests in detecting local cholestasis and can be used to monitor noninvasively the evolution of biliary obstruction. PMID- 7982657 TI - Fructose metabolism and cell survival in freshly isolated rat hepatocytes incubated under hypoxic conditions: proposals for potential clinical use. AB - The protective effect of fructose with regard to hypoxia-induced cell injury was investigated. The addition of fructose (2 to 20 mmol/L) protected hepatocytes against hypoxia-mediated cell lysis in a concentration-dependent way. The intracellular ATP content was initially decreased as a result of fructose-1 phosphate formation, but it remained constant during the hypoxic incubation. Conversely, high initial ATP values observed at low fructose concentrations progressively declined. Cellular protection was observed only when fructose was added before (and not after) the start of hypoxia. In addition, a sufficient amount of fructose-1-phosphate rapidly accumulated before the induction of hypoxia, and the linear production of lactate, during hypoxic incubation, indicated that cells synthesized ATP continuously. The lack of cell protection by fructose added after the onset of the hypoxia may be explained by a lesser fructose-1-phosphate formation and a subsequently low accumulation leading to insufficient glycolytic ATP production. Under aerobic conditions, both glycolysis (lactate formation) and gluconeogenesis (glucose formation) were carried out in fructose-1-phosphate-loaded cells with the same initial rates, whereas under hypoxic conditions glycolysis was the main metabolic event. The fact that protein synthesis activity recovered faster during reoxygenation of previously hypoxic fructose-treated cells than in glucose-treated cells led us to hypothesize that in situ perfusion of liver with fructose, before its removal, would improve its metabolic capacity during the hypoxic cold preservation and subsequent transplantation. PMID- 7982658 TI - Phenobarbital induction of alpha 1-acid glycoprotein in primary rat hepatocyte cultures. AB - The serum level of rat alpha 1-acid glycoprotein is significantly increased by treatment with phenobarbital, and in vivo studies have shown that phenobarbital seems to act mainly at the transcriptional level. To show the direct mediating effect of phenobarbital on alpha 1-acid glycoprotein gene expression, we investigated the ability of primary cultured rat hepatocytes to respond to in vitro phenobarbital administration. Phenobarbital increased both alpha 1 acid glycoprotein secretion and corresponding mRNA levels in primary rat hepatocytes cultured on matrigel. Used in combination with interleukin-1, interleukin-6 and dexamethasone, phenobarbital had an additive or synergistic effect on alpha 1 acid glycoprotein synthesis. These results show that (a) phenobarbital acts directly on hepatocytes by increasing alpha 1-acid glycoprotein gene expression and (b) this effect is mediated by a specific mechanism independent of pathways involved in alpha 1-acid glycoprotein induction by interleukin-1, interleukin-6 and glucocorticoids. PMID- 7982660 TI - Ursodeoxycholate protects oxidative mitochondrial metabolism from bile acid toxicity: dose-response study in isolated rat liver mitochondria. AB - The effect of ursodeoxycholate and tauroursodeoxycholate on the toxicity of lipophilic bile acids (chenodeoxycholate and lithocholate) on the function of the electron transport chain was investigated in isolated rat liver mitochondria. At a concentration of 30 mumol/L, both chenodeoxycholate and lithocholate reduced state 3 oxidation rates and respiratory control ratios of L-glutamate, succinate and duroquinol. In contrast, ADP/O ratios of these substrates and oxidative metabolism of ascorbate were not significantly affected. Ursodeoxycholate did not impair mitochondrial oxidative metabolism up to concentrations of 100 mumol/L; at 300 mumol/L, however, it decreased state 3 oxidation rates and respiratory control ratios of L-glutamate, succinate and duroquinol. Tauroursodeoxycholate had no significant inhibitory effect on state 3 oxidation rates of L-glutamate and succinate at concentrations up to 300 mumol/L. When ursodeoxycholate (final concentration, 30 mumol/L or 100 mumol/L) was added to mitochondrial incubations containing chenodeoxycholate or lithocholate, the toxic effects of lipophilic bile acids on mitochondrial oxidative metabolism were partially reversed. However, 300 mumol/L ursodeoxycholate, in combination with chenodeoxycholate or lithocholate, exhibited greater toxicity compared with incubations containing only the individual bile acids. In contrast to ursodeoxycholate, tauroursodeoxycholate did not reduce the toxic effects of chenodeoxycholate or lithocholate on mitochondrial metabolism. Ursodeoxycholate (100 mumol/L) significantly decreased the incorporation of chenodeoxycholate into mitochondrial membranes, whereas the decrease in lithocholate incorporation was not statistically significant. These studies demonstrate that ursodeoxycholate, but not tauroursodeoxycholate, decreases the toxicity of lipophilic bile acids on the function of the electron but increases bile acid-induced mitochondrial toxicity at higher concentrations.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7982659 TI - Effect of simvastatin, an inhibitor of hydroxy-methylglutaryl coenzyme A reductase, on the growth of human Ito cells. AB - During hepatic fibrogenesis, Ito cells proliferate, acquire a myofibroblastlike phenotype and synthesize increased amounts of extracellular matrix components. In this study, we have assessed the effects of simvastatin, an inhibitor of hydroxy methylglutaryl-coenzyme A reductase, on the growth of human myofibroblastlike Ito cells. Cells were grown from explants of normal human liver and characterized by a positive staining for desmin and smooth muscle alpha-actin. Simvastatin (0.1 to 10 mumol/L) induced a marked dose-dependent decrease of [3H]thymidine incorporation in human Ito cells, whether stimulated by human serum or by purified growth factors. Simvastatin-induced inhibition of DNA synthesis was confirmed by nuclear autoradiography and was not explained by a cytotoxic effect. The growth inhibitory effect of simvastatin was specifically due to inhibition of hydroxy-methylglutaryl-coenzyme A reductase because it was overcome by addition of mevalonic acid, the product of the enzymatic reaction. The reduction in [3H]thymidine incorporation was not affected by supplementation of culture medium with purified cholesterol-low-density lipoprotein or isopentenyl adenine. It was partially reversed by addition of farnesol. These results show that simvastatin decreases the growth of human Ito cells, independently of its effect on cholesterol synthesis. This decrease may be due in part either to reduced farnesylation of proteins involved in growth factor signaling pathway or to inhibition of N-linked protein glycosylation. Whether this effect exists in vivo and could thus lead to a parallel decrease of fibrosis deposition within the liver requires further study. PMID- 7982661 TI - Nonenzymatic glycosylation of poly-L-lysine: a new tool for targeted gene delivery. AB - The basic approach in targeted gene delivery relies on the formation of a complex between a vector and a molecule that will be selectively internalized by the target cells. In the case of hepatocytes, asialoglycoproteins are convenient targeting molecules because of the high affinity and avidity of the hepatocyte galactose receptor. In this system, poly-L-lysine is cross-linked to an asialoglycoprotein, and the resulting conjugate is complexed with the expression vector (DNA). The electrostatic binding between DNA and poly-L-lysine asialoglycoprotein ensures delivery of the intravenously injected complex to the liver, where it is subjected to endocytosis by hepatocytes. However, the poly-L lysine-asialoglycoprotein complexes tend to be unstable, of limited solubility and of fixed carbohydrate content. For these reasons we searched for a simpler alternative. We exploited the known capacity of reducing sugars to be reductively coupled to the epsilon-amino groups in proteins and used lactose to obtain poly-L lysine with "exposed" galactose. Glycosylation with sodium cyanoborohydride at high pH in borate buffer is a simple, reproducible procedure. The "lactosylated" poly-L-lysine has proved very stable, highly soluble and easily bound to plasmids. In a set of experiments we compared the asialofetuin-poly-L-lysine vector complexes with lactosylated poly-L-lysine vector complexes by transfecting hepatoma cells (HepG2) in culture. For these experiments we used a pRc/cytomegalovirus eukaryotic expression vector containing a mutant TGF-beta 1 complementary DNA.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7982662 TI - Neonatal capsaicin treatment does not prevent splanchnic vasodilatation in portal hypertensive rats. AB - It has been suggested that the peripheral sensory neurons are involved in the splanchnic hemodynamic changes of portal hypertension. Therefore the influence of permanent ablation of sensory neurons by neonatal capsaicin pretreatment (50 mg/kg, subcutaneously) on the development of the hyperdynamic splanchnic circulation in portal-hypertensive rats was studied. In adulthood, portal hypertension was induced with partial portal vein ligation. In study 1, systemic and splanchnic hemodynamics were measured by means of a radiolabeled-microsphere technique in portal-hypertensive rats, under ketamine anesthesia, pretreated with capsaicin or vehicle. Mean arterial pressure, heart rate, cardiac index, systemic and splanchnic vascular resistance, portal pressure, portal venous inflow, portal collateral resistance and portal-systemic shunting were not significantly different between capsaicin-pretreated and vehicle-pretreated rats. In study 2, gastric mucosal blood flow, measured by means of hydrogen gas clearance, and the hemoglobin and oxygen content of the gastric mucosa, as assessed with reflectance spectrophotometry, were not significantly different in the two groups of anesthetized portal-hypertensive rats pretreated with capsaicin or vehicle. In study 3, we confirmed the effectiveness of neonatal capsaicin pretreatment by measuring calcitonin gene-related peptide content of the gastric corpus wall. Capsaicin pretreatment caused a depletion of calcitonin gene-related peptide by at least 98% compared with that in vehicle-pretreated rats. These results do not support a role of capsaicin-sensitive sensory neurons that innervate the gastrointestinal tract in the development of the splanchnic vasodilatation characteristically observed in chronic portal hypertension. PMID- 7982663 TI - Function and regulation of UDP-glucuronosyltransferase genes in health and liver disease: report of the Seventh International Workshop on Glucuronidation, September 1993, Pitlochry, Scotland. PMID- 7982664 TI - A marriage of mice produces answers to old questions about man. PMID- 7982665 TI - Effects of high-normal and low-normal serum potassium levels on hepatic encephalopathy: facts, half-facts or artifacts? PMID- 7982666 TI - Dodging cellular customs: smuggling macromolecules into hepatocytes. PMID- 7982667 TI - Identifying the hepatic organic anion transporter: one of many? PMID- 7982668 TI - Anti-thyroid autoantibodies and hepatitis C virus. PMID- 7982669 TI - Thyroid abnormalities in patients with chronic viral hepatitis. PMID- 7982670 TI - Assessment of central blood volume in cirrhosis by radionuclide angiography: what does it really mean? PMID- 7982671 TI - Complications of transplantation for protoporphyric liver disease. PMID- 7982672 TI - Detection of Epstein-Barr virus small RNAs in routine paraffin sections using non isotopic RNA/RNA in situ hybridization. AB - The Epstein-Barr virus (EBV) is associated with an increasing range of reactive and neoplastic lesions. There is a need for a sensitive and specific method for detecting latent EBV in routine histological sections. We report the use of a highly sensitive paraffin section RNA/RNA in situ hybridization (ISH) technique using digoxigenin-labelled antisense riboprobes for demonstrating EBV encoded small RNAs (EBERs), EBV gene products that are transcribed in abundance during latent EBV infection. We applied EBER-ISH to 846 paraffin embedded specimens, including cases of reactive lymphoid hyperplasia (n = 28), infectious mononucleosis (16), Burkitt's lymphoma (44), immunodeficiency-associated lymphomas in transplant recipients (9) and AIDS patients (128), Hodgkin's disease (130), CD30 antigen positive lymphomas (106), peripheral T-cell lymphomas (104), sporadic B-cell non-Hodgkin's lymphomas (162), undifferentiated nasopharyngeal carcinoma (86), salivary gland lymphoepithelioma (11), and oral hairy leukoplakia (5). Strong, reproducible EBER staining was seen in EBV latently infected cells in archival surgical biopsy and autopsy specimens. EBER-ISH is specific, has a sensitivity comparable to that of the polymerase chain reaction, and is now the method of choice for the in situ detection of latent EBV infection. PMID- 7982673 TI - Primary non-Hodgkin's lymphoma of the intestine: a morphological, immunohistochemical and clinical study of 31 Chinese cases. AB - Thirty-one cases of primary non-Hodgkin's lymphoma of the intestine were investigated. Twenty-one were of B-cell and 10 of T-cell origin. The B-cell lymphomas comprised two cases of low-grade B-cell lymphoma of mucosa-associated lymphoid tissue (MALT), one of centroblastic/centrocytic type, three of high grade B-cell lymphoma coexisting with a low-grade B-cell lymphoma of MALT, nine of centroblastic, three of immunoblastic and three of Burkitt type. Of the T-cell lymphomas, eight were of pleomorphic medium-to large-sized cell type and two of large cell anaplastic type. All the B-cell lymphomas expressed CD20 (L26) and/or Ki-B5; in six there was monotypic immunoglobulin light chain restriction. Membrane positivity for CD45RO (UCHL1) was observed in the 10 cases of T-cell lymphoma, but the tumour cells did not express monocyte-macrophage markers. Clinically, the patients with T-cell lymphomas were usually young males with constitutional symptoms and their prognosis was significantly worse than those of patients with intestinal B-cell lymphoma. PMID- 7982674 TI - Information and observer disagreement in histopathology. AB - Concepts from information theory are used to assess the process of ordinal classification of histopathological continua such as degree of dysplasia or degree of differentiation. A working model is used to show that reducing the number of categories leads to an increase in inter-observer agreement, as measured by kappa statistics, but a decrease in information transmitted. It is argued that the prime role of histopathologists is to pass information, obtained from visual patterns, to the clinician and therefore more categories, rather than fewer, should be used. It is suggested that judgements of continua should be made on 100 point scales and quoted together with 95% confidence limits; and that the judgements of different observers should be averaged to form a reference range. PMID- 7982675 TI - Bone marrow trephines. Findings in patients with hairy cell leukaemia before and after treatment. AB - Bone marrow trephine biopsies from 20 patients with hairy cell leukaemia were reviewed at diagnosis and during therapy with alpha-interferon (IFN) and with 2 chlorodeoxyadenosine (2-CdA). At time of diagnosis the trephines revealed classical features of hairy cell leukaemia and profound alterations of haematopoiesis. All three lines showed dysplastic features with architectural, qualitative and quantitative changes. Review of consecutive trephine biopsies in patients that received IFN showed that a complete remission with disappearance of the tumour was never achieved and that the dysplastic features persisted. An improvement of haematopoiesis was noted, but recovery, especially of the myelopoiesis, was never completely achieved. By contrast, patients treated with 2 CdA de novo and previously treated with IFN achieved a complete remission in all but three cases. The trephine biopsies showed an improvement of haematopoiesis with progressive disappearance of the dysplastic features and a good recovery of myelopoiesis. A residual lymphocytosis was present, but as it was also present in age-matched control cases it could not be considered as a residual tumour. The disappearance of the leukaemic infiltrate probably constitutes a prerequisite for the recovery and normalization of haematopoiesis, while the dysplastic changes present at diagnosis could be the result of cytokine production by the leukaemic cells. PMID- 7982676 TI - Apoptosis of bile duct epithelial cells in hepatic allograft rejection. AB - Liver biopsy remains the 'gold standard' for monitoring rejection in liver transplant patients. Portal inflammation, bile duct damage and endothelialitis are recognized features of hepatic allograft rejection. The pathogenesis of the bile duct injury during rejection, however, remains unclear. To define the mechanism of bile duct damage, we studied the light- and electronmicroscopic appearance of hepatic tissue from selected patients in whom allograft failure was solely due to rejection. Of the 25 orthotopic liver transplant rejection cases examined, 17 were mild, seven were moderate and one was severe rejection. Light microscopy examination of the damaged bile duct epithelium revealed evidence of apoptosis which was confirmed by electronmicroscopy. Furthermore, there appeared to be a positive correlation between the grade of rejection and the number of apoptotic cells. Also included in the study were 13 cases of chronic active hepatitis and 10 normal livers which showed the least apoptotic cells. We conclude that the identification of apoptotic cells in damaged bile ducts in allograft biopsies might be helpful in the diagnosis of rejection and in assessment of the severity of rejection. PMID- 7982677 TI - Amputation neuroma of the hepatic hilum after orthotopic liver transplantation. AB - Amputation neuromas following biliary surgery have been previously reported. There are no descriptions, however, of amputation neuroma following liver transplantation. Serial hilum sections taken from 93 hepatectomy specimens obtained during the clinical course of 262 consecutive orthotopic liver transplantations revealed 26 amputation neuromas (27.9% of the specimens examined). The finding was confirmed by immunohistochemistry with numerous S-100 protein positive cells intermingled with neurofilaments interrupting the perineurial layer of cells testing positive for epithelial membrane antigen. Neuromas were found in liver specimens obtained between 89 and 775 days post transplant (mean time, 211 days). The incidence of neuroma was higher in specimens resected more than 3 months post-transplant. There was only one symptomatic patient, who died from extrahepatic cholestasis demonstrated at autopsy to be caused by a hilar neuroma obstructing the main bile duct. PMID- 7982678 TI - Enlargement of the carotid bodies in cirrhosis of the liver. AB - The carotid bodies were dissected out at necropsy and weighed in seven subjects with cirrhosis of the liver and in seven control subjects of comparable age free of liver disease. The mean combined carotid body weight of the control group was 17 mg but in the cirrhotic patients it was 35 mg, a statistically significant difference (P < 0.005). Differential counts of the various types of glomic cell (progenitor, dark and light variants of chief cells and sustentacular cells) were carried out. The enlargement of the carotid bodies in the subjects with cirrhosis was associated with increased numbers of the dark variant of chief cell. The mean number of dark cells per unit area in the control group was 361 cells/mm2 but in the cirrhosis group it was 1024 cells/mm2, a statistically significant difference (P < 0.005). It is postulated that the prominence of dark cells may be associated with secretion of a natriuretic peptide in response to the hyperaldosteronism and sodium retention of cirrhosis of the liver. Alternatively, it may be a response to hypoxaemia resulting from porta-pulmonary shunts. PMID- 7982679 TI - Plexiform fibrohistiocytic tumour with novel phenotypic features. AB - Plexiform fibrohistiocytic tumour is a recently described type of fibrohistiocytic tumour, the differentiation pattern of which is poorly understood. A case representing the predominantly fibrohistiocytic type of the tumour is reported. Immunohistochemical analysis supports the histiocytic origin of this entity. The expression of EBM/11 and tissue transglutaminase both in fibroblast-like and histiocyte-like cells indicate that a single cell line produces the dual morphological features. It is proposed that a non-phagocytic epithelioid pattern of histiocytic differentiation characterizes this tumour. PMID- 7982680 TI - Mixed pulmonary blastoma and carcinosarcoma. AB - Pulmonary blastomas and carcinosarcomas are uncommon tumours, accounting for less than 1% of all lung neoplasms. Three previously described mixed epithelial and mesenchymal tumours having both adult and embryonal elements were termed 'transitional'. We report a similar case and evaluate the application of the term 'transitional tumour'. PMID- 7982681 TI - Nodular transformation of splenic red pulp due to carcinomatous infiltration. A diagnostic pitfall. AB - Autopsy of three women dying of disseminated carcinoma of stomach, colon, and breast, respectively, revealed a grossly unremarkable spleen. Microscopic examination demonstrated a nodular transformation of the red pulp, simulating a follicular lymphoma. Immunostaining revealed dissociated carcinomatous cells between the nodules, and this was thought to be the cause of the nodular transformation. PMID- 7982682 TI - Basaloid squamous cell carcinoma of the palate. PMID- 7982683 TI - Subungual keratoacanthoma. PMID- 7982684 TI - Compound medullary-papillary carcinoma of the thyroid: true mixed versus collision tumour [corrected]. PMID- 7982685 TI - Ovarian haemangiomas and stromal luteinization. PMID- 7982686 TI - Lymphohistiocytic T-cell lymphoma. PMID- 7982687 TI - State purchasing cooperatives for psychotropic medication. PMID- 7982688 TI - Collaboration between social work and psychiatry in aftercare in the early 1900s. PMID- 7982689 TI - Screening and treatment of tuberculosis in a methadone maintenance treatment program. PMID- 7982690 TI - Postmortem of the Rochester capitation experiment. PMID- 7982691 TI - Down and out in New York and London: a cross-national comparison of homelessness. AB - OBJECTIVE: This study compared homelessness in New York City and London to examine the relative roles of individual pathology and structural forces in causing homelessness, the effect of sociopolitical and cultural differences on policy decisions toward solving homelessness, and the effect of broader structural forces on service programs for the homeless. METHODS: A review of the scholarly literature and news reports was combined with interviews of staff members and homeless persons associated with various community agencies in London and New York City. Homelessness in the two cities was compared in relation to definition, demography, nonpsychiatric and psychiatric etiological factors, public policy, governmental responses, financial support, service strategies, and the practicalities of securing services and entitlements. RESULTS AND CONCLUSIONS: The results indicate that characterizations of homelessness as a trait rather than a state reflect the tensions between social justice, public concepts, and a nation's economic resources. The absolute numbers of homeless persons, including those who are mentally ill, primarily reflect structural factors such as the availability of low-cost housing and public benefits. The commonalities that mentally ill homeless persons share with other vulnerable groups generally outweight their differences. The statutory rights to entitlements may be vitiated in times of shortage, especially for the least capable citizens. In both countries, efforts have been made to use the voluntary sector to serve the homeless, although it has been used much more extensively in Britain. PMID- 7982692 TI - What CMHCs can learn from two states' efforts to capitate Medicaid benefits. AB - If the Clinton health care reform package becomes law, community mental health centers will face challenges similar to those recently encountered by centers in several states under new Medicaid initiatives to capitate payments for mental health care. The authors summarize experiences and research findings from centers in two states using two different models: in Minnesota, a mainstreaming model in which Medicaid contracted with health maintenance organizations (HMOs) to provide all physical and mental health care for its beneficiaries, and in Utah, a mental health HMO model in which community mental health centers signed contracts to serve as mental health HMOs for Medicaid beneficiaries. Several implications for CMHCs under managed competition are discussed, including the need for centers to play a strong, proactive role in the establishment of benefit alternatives and enrollment processes and the need to implement aggressive policies to manage service utilization. PMID- 7982693 TI - Factors complicating cost containment in the treatment of suicidal patients. AB - OBJECTIVE: The treatment of suicidal patients contributes to escalating mental health expenditures. Fiscal realities necessitate that cost-containment measures be implemented wherever possible. The authors reviewed the literature to delineate factors that impede cost containment for the treatment of suicidal patients and to outline strategies for controlling costs while improving the quality of care. METHODS: Psychological Abstracts and MEDLINE databases were reviewed. Retrieval and analysis focused on literature published between 1982 and 1992. RESULTS AND CONCLUSIONS: Five factors unique to the treatment of suicidal patients that impede cost containment were identified: the lack of a specific and cost-effective screening method to determine true risk of suicide, the high number of parasuicidal and malingering patients, revolving-door admissions of involuntary patients who become noncompliant with treatment after discharge, the adverse clinical consequences of further increases in existing discriminatory mental health benefits, and the medicolegal liability incurred in treating suicidal patients. The low frequency of completed suicides in relation to attempts and reported ideation indicates that most inpatients labeled suicidal are hospitalized unnecessarily. Thus inpatient treatment should be reserved for patients who make attempts of high lethality and patients with suicidal ideation who are at high risk because of other factors. Ideally, suicidal patients should be committed not to an inpatient facility but to a treatment network in which they can move appropriately between inpatient, day hospital, and outpatient care. PMID- 7982694 TI - Continuous quality improvement: conceptual foundations and application to mental health care. AB - Continuous quality improvement (CQI), a philosophy and a set of techniques for managing the quality of services in health care, involves procedures for defining an organization's goals and work processes and applying quantitative measures of quality focused on patient outcome. To successfully adapt CQI to specific mental health care settings, staff must understand the attitude, approach, and processes that distinguish CQI and must address the challenges of defining quality within mental health care and coordinating the efforts of multidisciplinary treatment teams. After detailing the development of the conceptual underpinnings of CQI, the author uses an example of implementation of CQI on a unit for chronic mentally ill patients at a state psychiatric hospital to show how these challenges can be addressed by reconceptualizing and specifying the treatment mission. PMID- 7982695 TI - Jail recidivism and receipt of community mental health services. AB - OBJECTIVE: The authors' aim was to test the relationship between receipt of desired community mental health services by homeless mentally ill forensic clients and whether the clients returned to jail within six months. METHODS: Mentally ill homeless clients leaving jail were randomly assigned to three service conditions: intensive case management provided by an assertive community treatment team, intensive case management provided by individual case managers, and referral to a community mental health center. Data on whether clients' service needs were met were analyzed using discriminant function and chi square analyses. RESULTS: Thirty-two percent of the 105 clients interviewed at six months were reincarcerated during the six-month study period. Jail recidivism was related to receipt of fewer services that clients reported they needed, specifically to receipt of fewer services for developing independent living skills. Service condition was not significantly related to return to jail. CONCLUSIONS: Case management, a flexible community-based service that does not lend itself to clearly prescribed procedures, may easily deteriorate into providing monitoring rather than rehabilitative services for forensic clients and thus may facilitate reincarceration. PMID- 7982696 TI - Characteristics of African-American and white patients with panic disorder and agoraphobia. AB - OBJECTIVE: The authors explored the clinical characteristics and treatment response of African-American and white patients with panic disorder and agoraphobia who presented for treatment at an anxiety disorders clinic. METHODS: One hundred white and 43 African-American patients were evaluated using a structured interview and completed a variety of standardized rating scales. In addition, data regarding clinical characteristics, psychiatric history, childhood history, life stressors, and treatment outcome were obtained by chart review. The incidence of isolated sleep paralysis was also assessed in a subsample of patients. RESULTS: The two groups had no significant differences in psychiatric symptoms. African-American patients were more likely to use a medical emergency room, to have had childhood separations, and to have had parents who abused substances. They also reported less separation anxiety, school phobia, and affective illness in family members. In addition, African Americans, both patients and nonclinical control subjects, were more likely to report that they experienced repetitive episodes of isolated sleep paralysis. Treatment outcome was moderately successful among both African-American patients and white patients. CONCLUSIONS: Although African-American and white patients show similar symptoms of panic disorder, African-American patients had more unnecessary psychiatric hospitalizations, a higher rate of medical emergency room visits, a higher incidence of isolated sleep paralysis, greater likelihood of childhood trauma, and a greater number of life stressors. Addressing these issues in treatment is critical in reducing the dropout rate and maintaining successful treatment. PMID- 7982697 TI - Sociodemographic characteristics of dropouts from a child guidance clinic. AB - OBJECTIVE: This study examined the characteristics of families who dropped out and families who maintained contact with a children's psychiatric outpatient clinic through various phases of intake and treatment. METHODS: One year after intake, the authors examined the status of all patients (N = 555) who had sought treatment at an urban, university-affiliated children's psychiatric outpatient clinic over a two-year period and had completed the intake process. Factors associated with dropout were identified at four points in the clinic process: during intake, during evaluation, at completion of evaluation, and during treatment. RESULTS: Urban residence, minority status, single-parent status, and Medicaid status were related to dropout at intake and during evaluation but not at subsequent clinic phases. Nonminority, two-parent, suburban families of higher socioeconomic status were more likely to drop out at the completion of the evaluation. CONCLUSIONS: These results indicate that factors associated with attrition vary with the clinic phase. Further investigations of the clinical course of minority children and families involved with children's mental health services are necessary to understand the needs of this population and to design interventions such as increasing minority staff and providing training in multi cultural competence. PMID- 7982699 TI - An overview of organizational and occupational psychiatry. AB - Although many clinicians agree in principle that work is central to personal identity and mental health, issues related to patients' experiences in the workplace have not been a central focus in clinical practice in psychiatry. However, the link between work and mental health continues to be confirmed by research, and interest in occupational and organizational psychiatry, which focuses on the psychopathology that the individual brings to the workplace and that results from the individual's experiences in the workplace, has increased in the past decade. The three main areas of practice in the field--direct clinical services, consultation, and applied research--include evaluating work-related psychiatric disability, providing case management for employees who receive psychiatric treatment, evaluating a candidate for an executive position, and conducting epidemiological research about stress-related disorders. A patient's occupational or work history can provide valuable information for routine psychiatric diagnosis and treatment planning. PMID- 7982698 TI - Family costs associated with severe mental illness and substance use. AB - OBJECTIVE: The study's aim was to document the economic assistance in the form of money, in-kind contributions, and time spent in care-giving by families of adults with both severe mental illness and substance use disorders. METHODS: A total of 119 families of adults with dual disorders were compared with a similar group of 127 families whose adult children had no chronic illnesses. In telephone interviews, parents reported the amount of money, goods, and direct care family members gave to a designated adult child. Two methods were used to estimate the value of family time: opportunity costs, based on the average wage for production workers in the study area, and the cost of paid substitutes for the task being performed. RESULTS: Parents of adults with dual disorders reported that family members gave significantly more money and time to the adult child than did parents of adults with no chronic illnesses. The estimated value of family assistance in the dual disorder group was $9,703 using the opportunity-cost method and $13,891 using the substitution method, compared with costs of $2,421 and $3,547 for the group with no chronic illnesses. CONCLUSIONS: Dual disorders impose a significant economic burden on families. Direct support that families provide to adult children with dual disorders should be considered carefully in treatment planning and policy decisions. PMID- 7982700 TI - Wilhelm Griesinger and the concept of community care in 19th-century Germany. AB - Wilhelm Griesinger, a 19th-century German physician, can be considered one of the founders of the concept of community-based care for mentally ill patients. In an era when such patients typically spent most of their lives in asylums in remote rural areas, be recommended their integration into society and proposed that short-term treatment of acutely ill patients could be carried out in asylums that were located in cities and linked to general hospitals. He believed that short term hospitalization could be effective only if professional and natural support systems cooperated closely. Although he did not assume that all mental illnesses could be cured, he thought that most patients should be discharged from long-term treatment in remote asylums. For those unable to live without support in the community, be suggested setting up sheltered living conditions. Although his ideas about community-based care were rejected by his contemporaries in favor of a system of rural asylums, many of Dr. Griesinger's suggestions are now being put into practice. PMID- 7982701 TI - A comparison study of patient falls in a psychiatric setting. PMID- 7982702 TI - Computerized treatment planning. PMID- 7982703 TI - Current perspectives on multiple personality disorder. PMID- 7982704 TI - Behavioral group therapy. PMID- 7982705 TI - Minimizing violence. PMID- 7982706 TI - Clozapine and chemotherapy. PMID- 7982707 TI - Making clozapine available. PMID- 7982708 TI - Congressional briefing calls attention to mental health needs of African Americans. PMID- 7982709 TI - New plan for homeless proposes major changes to improve coordination and access to services. PMID- 7982710 TI - [Azithromycin--an innovative macrolide antibiotic for 3-day-therapy]. PMID- 7982711 TI - [Cefepim--profile of a new cephalosporin]. PMID- 7982712 TI - [Cold labile serum and plasma proteins: clinical and diagnostic significance of cryoglobulins, cryofibrinogen and cold agglutinins]. AB - Cold labile serum and plasma proteins can cause a variety of clinicopathological symptoms. Due to altered physicochemical properties, cryoglobulins and cryofibrinogens may cause increased serum viscosity, cold dependent protein precipitation or, in rare cases, serum gelification. Cold agglutinins, on the other hand, cause temperature dependent agglutination of erythrocytes and eventually hemolysis. All pathological cold dependent serum and plasma phenomena are associated with either neoplasma, autoimmune disorders, various infections or are considered as "essential". While the diagnosis of these conditions remained largely unchanged during the last 10 years, new aspects regarding etiology, pathogenesis, and therapy have arisen. PMID- 7982713 TI - [Extracellular enzymes of Pseudomonas aeruginosa as virulence factors]. AB - Pseudomonas aeruginosa is an opportunistic pathogen causing a variety of diseases, especially in immunocompromised patients like those suffering from cystic fibrosis (CF) where these bacteria preferentially colonize the bronchopulmonary tract. A high intrinsic antibiotic resistance and its ability to synthesize and secrete numerous different virulence factors are regarded as biological properties contributing to the pathogenicity of P. aeruginosa. Among the virulence factors are many enzymes which have been characterized in detail with respect to their molecular properties. Environmental factors regulating the synthesis and release of extracellular enzymes have been identified as e.g. the concentration of Fe- and PO4-ions, choline, pH, and osmolarity. In addition, low molecular weight substances named autoinducers were identified as regulators which are synthesized by the bacteria. Therefore, P. aeruginosa represents an example for the remarkably complex relationship between pathogenic bacteria and their human host. PMID- 7982714 TI - [Laboratory diagnosis of parvovirus B 19 infection: comparison of ten commercial IgG- and IgM-antibody tests]. AB - Seven ELISAs, two westernblots and one immunofluorescence assay for serological detection of parvovirus-B19-infection were compared with regard to their sensitivity and specificity. All ten assays are commercially available and use recombinant proteins (VP1, VP2) from bacterial and eukaryotic expression systems and synthetic viral peptides as antigens. The ELISA assays comprise indirect ELISA and mu-capture systems. All assays were tested for their sensitivity with follow-up sera from 21 patients with acute parvovirus B19 infections. The specificity was analysed by 194 sera from pregnant women and from patients with acute other virus infections or rheumatoid factors, but without acute parvovirus infection. Only three ELISAs, both westernblots and the immunofluorescence assay can be recommended for the IgG-measuring (prevalence). For the detection of an acute parvovirus infection, especially during pregnancy, two ELISAs show good IgG and IgM-results, one ELISA is less recommendable and all other assays show only a poor IgM-specificity. PMID- 7982715 TI - [Endocarditis from Erysipelothrix rhusiopathiae]. AB - Erysipelothrix rhusiopathiae only seldom causes cases of endocarditis. Contact with infectious animals leads to endocarditis of the left heart with high lethality. Vancomycin and aminoglycosides, which are often used in gram-positive endocarditis, show no effect. PMID- 7982716 TI - [Streptococcal myositis in children: four case histories]. AB - We report about four children, who suffered from myositis caused by beta hemolytic group A streptococci (GAS). The cases were observed during the last 12 months, and differed much in severity. Soft tissue infections caused by GAS are reported with increasing frequency from the USA, Australia and Europe. They occur in hitherto healthy children and young adults, mostly without a predisposing trauma. In children, a preceding varicella infection is often found. Some patients develop a streptococcal toxic shock syndrome with a letality of 20-50%. The bacteria, which can be isolated from normally sterile body sites, are morphologically inconspicuous, and are mostly of the serological type M1 or M3. PMID- 7982717 TI - Human MCF activates monocytes to produce IL-1 but not TNF or CSF-1. AB - Monocyte cytotoxicity inducing factor (MCF) is a novel cytokine which was originally characterized by its ability to induce monocyte cytotoxicity against tumor targets. The present studies were undertaken to define the mechanisms of cytotoxicity. Since the cytotoxic state may be mediated, in part, by the secretion of monokines, MCF's effect on IL-1, TNF and CSF-1 were measured. MCF caused human peripheral blood monocytes to secrete large amounts of IL-1 but not TNF. In contrast monocytes produce CSF-1 in culture and this production was not enhanced by MCF. IL-1 neither appeared to directly lyse the target K562 nor was able to activate macrophages for cytotoxicity. However, IL-1 may be necessary for lysis of K562 by activated macrophages through its cytostatic effect on K562. MCF increased monocyte surface expression of DR-beta (when studied by fluorescent microfluorometry) and messenger RNA for DR-beta after 24 h in culture. These functional studies indicate that MCF is a cytokine with a distinct spectrum of biologic activities whose functions may be mediated by synthesis and secretion of IL-1. PMID- 7982718 TI - Enhancement of B cell function as antigen-presenting cell during interplay with Th cells. AB - We have previously reported that C57BL/6 mouse B cells present Ag to an I-Ab restricted and OVA-specific T cell clone, 34-7F, to secrete IL-2 but not to proliferate, whereas spleen adherent cells as APC induce a proliferative response of 34-7F cells to OVA. In this T cell response, it was examined whether B cells were stimulated during presenting Ag and acquired the ability as APC to induce proliferative Ag-response of 34-7F cells. For this aim, B cells prepared from unstimulated mouse spleen cells were cultured with 34-7F cells in the presence of OVA and then compared with unstimulated B cells for APC function in the OVA response of 34-7F cells. Unstimulated B cells proliferated when cultured for 2 days with irradiated 34-7F cells and OVA, and the proliferation was inhibited by an anti-I-Ab mAb. B cells which had been stimulated for 2 days with 34-7F cells and OVA induced an increase in phosphatidyl inositol metabolism in 34-7F cells in the presence of Ag, whereas unstimulated B cells failed to do so. The increase was dependent on the dose of OVA and on the number of the stimulated B cells. Ag presentation by the stimulated B cells (but not by unstimulated ones), also induced IL-2R expression on 34-7F cells, which resulted in IL-2-dependent proliferation. The IL-2R expression does not depend on the possible increase in IL-2 production by the T cells, inasmuch as the activated B cells induced lower expression of IL-2 mRNA or lower secretion of IL-2 by 34-7F cells than that induced by unstimulated B cells. These results suggest that B cells receive signal(s) from 34-7F cells to enhance APC function during Ag-presentation to the T cells which do not proliferate in the response to Ag on unstimulated B cells, and that the stimulated B cells induce the proliferative response of 34-7F cells to OVA. PMID- 7982719 TI - Characterization of a chemically induced tumor model and the effects of natural killer cell depletion by antiasialo GM-1. AB - A tumor model in the Sprague-Dawley rat has been developed and characterized in our laboratory using the polycyclic aromatic hydrocarbon 3-methylcholanthrene (3MC). Interactions between the tumorigenic process and the natural killer cell (NK) response were investigated in this study. Rats given a single injection of 1.5 mg 3MC had reduced NK activity the first three weeks after injection when compared to vehicle treated controls. Tumor incidence in this group reached 45% and 76% 12 and 20 weeks, respectively, after the 3MC injection. Cell lines were established from six of these tumors and were tested for in vitro lysis by NK cells. Sensitivity of these cells ranged from 2.9 to 12.2% compared to 32.3 to 37.5% for the NK sensitive YAC-1 target cells. Rabbit antiasialo GM-1 antibody (ASGM-1) was used to effect in vivo reductions of NK function at arbitrarily selected times after 3MC injection. Tumor incidence in the group of rats treated to reduce NK activity at the time of initiation (0-2 weeks) reached 100% in 20 weeks compared to 67% in the companion 3MC treated controls. The number of days to tumor was also decreased from 93 to 77 days in this group. Rats treated to reduce NK activity at other times (5-7 weeks or 10-12 weeks) did not have alterations in tumor incidence or latency that were different from controls. The study supports a role for NK cells in the early detection and removal of transformed cells and points out the dangers of transient immunosuppression. PMID- 7982720 TI - In vivo administration of interleukin-6 in murine allogeneic bone marrow chimeras: early and delayed enhancement of hematopoiesis accompanied with split tolerance but not with graft-versus-host disease. AB - Interleukin-6 (IL-6) induced increased, leukocyte and platelet counts on around day 20 when it was administered into [BALB/c-->C3H/He] bone marrow chimeras from day 1 to day 12. Increased leukocyte counts and hemoglobin (Hb) levels were also observed at around day 60 and from day 41 to 80, respectively. On the other hand, hematopoietic recovery in [C3H/He-->C3H/He] bone marrow chimeras injected with IL 6 was different from that in [BALB/c-->C3H/He] bone marrow chimeras, showing no delayed and long-lasting increase in Hb levels but showing an early and transient increase in Hb levels and platelet counts. Sera from [BALB/c-->C3H/He] bone marrow chimeras injected with IL-6 showed predominant productions of IL-3 and/or IL-4. Reverse transcriptase polymerase chain reaction (RT-PCR) showed that stem cell factor (SCF) mRNA expression was increased in bone marrow or spleen cells from [BALB/c-->C3H/He] bone marrow chimeras injected with IL-6 on day 36. Furthermore, we analyzed influence of IL-6 on graft-versus-host disease (GVHD) in [BALB/c-->C3H/He] bone marrow chimeras injected with IL-6. Decreased survival days and body weights were not observed when compared with the control. Histopathological changes of the liver due to GVHD were also not obvious. However, alloreactive mixed lymphocyte reactions (MLRs) were readily detected although cytotoxic T cells were not generated. Since H-2 typing showed that donor type chimerism was predominantly observed, it was suggested that split tolerance might be induced by IL-6 administration. Increased IL-2 levels were not detected in sera from [BALB/c-->C3H/He] bone marrow chimeras injected with IL-6 whereas IL 4 was detected in the same sera, indicating that type 2 helper T (TH2) cells appeared to be predominantly generated. These results suggest that IL-3/IL-4 and SCF appeared to synergistically support delayed effects on hematopoiesis in [BALB/c-->C3H/He] bone marrow chimeras injected with IL-6 although early effects appeared to be mediated mainly by IL-6 directly or indirectly. Furthermore, IL-6 could induce split tolerance in [BALB/c-->C3H/He] bone marrow chimeras via a preferable activation of TH2 type cells without inducing severe GVHD. PMID- 7982721 TI - Effects of direct current on T cell activity: modulation of interleukin-2 production. AB - The production of interleukin-2 (IL-2) by mitogen-stimulated human peripheral blood leukocytes (PBL) was significantly enhanced by a short pretreatment of PBL with direct current (DC) at low intensities. Exposure of PBL to DC of 1 mA for more than 10 min resulted in inhibition of IL-2 production which correlated with decreased proliferation capacity of the treated cells. DC had similar enhancing and inhibitory effects on IL-2 production by the mitogen-stimulated human leukemia T cell line MOLT-13. However, DC itself did not stimulate IL-2 production in PBL or in MOLT-13 cells. In two additional T cell lines tested, MOLT-16 and H-9, DC did not enhance mitogen-stimulated IL-2 production, but suppressed it when applied at 1 mA for more than 10 min. Both the mitogen stimulated and the interleukin-1 (IL-1)-enhanced IL-2 production were completely inhibited by 1 mA of DC applied for 20 min. The observed effects of DC were due to a direct action of DC on the cells and not to possible effects of the secondary by-products of electrolysis. These results show that pretreatment of cells with DC can enhance or suppress IL-2 production depending on the intensity of DC and the type of IL-2 producing cell clones. PMID- 7982722 TI - Immunocytochemical demonstration of prostaglandin synthase (cyclooxygenase) in thymic macrophages of normal and cyclosporin-treated rats. AB - As revealed with ED1 and ED2 monoclonal antibodies, macrophages are scattered throughout the thymic tissue. However, in contrast to the cortex and medulla, in the cortico-medullary zone macrophages are large and show strong reactivity with rabbit polyclonal antisera to cyclooxygenase. Only few smaller cortical macrophages also show weaker presence of prostaglandin synthase. After cyclosporin treatment cortical macrophages become strikingly similar to the macrophages of the cortico-medullary zone of the normal thymus. Cortical macrophages become enlarged and develop the strong expression of prostaglandin synthase. Our results show that a specific type of macrophages (with distinct histochemical characteristics, enzyme profile and ultrastructural organization, which is strategically positioned within the thymic tissue--as we demonstrated earlier) possesses the enzyme capacity required for prostaglandin synthesis. After cyclosporin treatment, which interferes with the maturation of thymocytes, cortical macrophages thoroughly change and develop the strong prostaglandin synthase expression, similar to that of normal cortico-medullary zone macrophages. PMID- 7982723 TI - Mannan-binding protein-like activity in the sera of newborn piglets. AB - The mechanism of the antibody-independent bactericidal activity of the sera of newborn piglets deprived of colostrum was studied using rough strains of E. coli and S. typhimurium. Although all strains were invariably killed by all newborn piglet sera tested, two different mechanisms of killing were encountered. Using specific anti-pig C1q antiserum, strains S. typhimurium LT2Ml and E. coli K-12, strain Gal 23 were found to be killed by a C1q-dependent mechanism, while the killing of E. coli S 16, E. coli K-12, strain W 3100 and E. coli B 41 could not be inhibited by anti-C1q antiserum. In order to test whether a mannan-binding protein is responsible for the bactericidal effect in the latter group of strains, we examined the inhibitory activity of two types of mannans isolated from S. cerevisiae and H. capsulata, respectively. The use of a purified rabbit mannan-binding protein showed that only strains killed by the C1q-independent mechanism were sensitive to the MBP-dependent mechanism of killing, the inhibitory activities of both mannans were found to be equal. As expected, the inhibitory effect of mannan on the bactericidal activity of newborn piglet sera was also detected only in strains killed by the C1q-independent mechanism. Surprisingly, only the phosphomannan isolated from H. capsulata was found to be an effective inhibitor of the bactericidial activity of piglet sera against E. coli S 16 and E. coli K-12, strain W 3100, while the mannan isolated from S. cerevisiae was inactive. Hence the factor present in newborn piglet sera is either MBP with slightly different binding properties, or a completely different protein. PMID- 7982724 TI - Protective cellular immunity against a spontaneous mammary carcinoma from ras transgenic mice. AB - Mammary carcinomas of v-Ha-ras transgenic mice closely resemble human breast cancer in their multi-step nature and in the requirement of genetic, hormonal and somatic mutational events for full-scale malignancy. We demonstrate that spontaneous breast cancers derived from v-Ha-ras transgenic FVB (H-2q) mice are highly immunogenic and that they elicit a protective T cell response. A continuous tumor cell line OM-2 has been established from a progressively growing mammary tumor and three sublines OM-10, OM-12 and OM-14 have been derived by in vivo passage of OM-2. All lines express the v-Ha-ras gene product and surface MHC class I. The parental OM-2 line is highly immunogenic and behaves like a regressor tumor. The regression of OM-2 is mediated by CD8+ T lymphocytes, although CD4+ lymphocytes also appear to play a limited role. Cytotoxic T lymphocytes (CTLs) obtained from mice immunized with OM-2 show MHC class I restricted, specific T cell cytotoxicity against OM-2 but not normal fibroblasts derived from ras transgenic mice. The anti-OM-2 CTLs lyse the OM-2 sublines OM-12 and OM-14, although to a lesser degree than OM-2, and do not lyse OM-10, in spite of the fact that all cell lines express comparable levels of activated ras and MHC class I. Our studies represent the first analysis of protective T cell response to breast cancer and demonstrate that contrary to expectation, the spontaneous breast cancers are highly immunogenic and that the immune response does not appear to be directed to activated ras. PMID- 7982725 TI - Sex difference in the serostatus of adults to the Epstein-Barr virus. AB - A total of 1047 adults, aged between 18 and 90 years, including blood donors and surgical patients of the Medical University of Lubeck in Germany, were screened for IgG antibodies to the Epstein-Barr Virus, either by standard indirect immunofluorescence or by a novel enzyme-linked immunosorbent assay (Enzygnost Anti-EBV/IgG, Behring, Marburg, Germany). There was a significant sex difference in the serostatus to the Epstein-Barr virus in adults. Male adults were more likely than females (p < 1%) to be EBV-seronegative. The same trend was seen in both a group of 713 blood donors and 334 surgical patients and when different test methods were used. However, this sex difference was not shown in the sera of 86 pediatric patients of the Medical University of Lubeck tested by indirect immunofluorescence for IgG antibodies to the Epstein-Barr virus. Furthermore, titers of IgG antibodies to Epstein-Barr virus specific antigens of female adults, obtained by the enzyme-linked immunosorbent assay (Enzygnost Anti EBV/IgG), had significantly higher median values than male adults (p < 5%). PMID- 7982726 TI - Release of monokines by pulmonary macrophages following antigen challenge in sensitized guinea pigs. AB - Guinea pigs were passively sensitized with immune serum to ovalbumin (OA), control serum, or saline. Twenty-four hours later, they inhaled aerosols of OA (2% in saline), saline, or lipopolysaccharide (LPS). Following anesthesia, bronchoalveolar lavage (BAL) was performed at 30, 60, 90 and 120 min postinhalation. Alveolar macrophages (AM) were isolated from the BAL fluid and incubated (18 h) in medium alone or with zymosan (1 mg/ml). Supernatants were collected and levels of interleukin-1 (IL-1), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-alpha) determined by bioassays. Unstimulated AM from animals that inhaled OA, saline, or LPS secreted similar amounts of IL-1 at 30, 60, and 90 min postinhalation. Zymosan (1 mg/ml) significantly increased IL-1 secretion by AM collected at 60 and 90 min from OA-sensitized animals that inhaled OA or saline. AM from guinea pigs sensitized to OA that inhaled OA or LPS secreted significantly increased amounts of IL-6 at 30, 60, 90, and 120 min postchallenge compared to saline sensitized controls. In all groups, AM from LPS treated animals secreted large amounts of TNF-alpha at all sampling times postchallenge; AM from OA-sensitized and challenged animals secreted increasing amounts of TNF-alpha with time postchallenge, spontaneously and in response to zymosan. By contrast, AM from saline sensitized and challenged guinea pigs did not release detectable amounts of TNF-alpha spontaneously and secreted very low amounts in the presence of zymosan. These findings show that antigen challenge results in a rapid activation of AM isolated from BAL and suggest AM may initiate the development of inflammatory processes associated with antigen challenge. PMID- 7982727 TI - Role of eosinophilic granulocytes in women with infertility and pelvic adhesions. AB - Increased numbers of eosinophilic granulocytes and eosinophil degranulation have been observed in various inflammatory conditions. Biopsies from the fallopian tubes of 28 patients were examined for the content of eosinophilic granulocytes. Peritoneal fluids (PF) from 89 patients were analyzed for the concentrations of eosinophilic granulocytes and the granule protein eosinophil cationic protein (ECP). The ECP levels in the PF were substantially elevated during genital inflammation (P < 0.001). Furthermore, one week after laparotomy for adhesiolysis there were both increased PF-ECP levels (P < 0.01) and raised concentrations of eosinophilic granulocytes (P < 0.001) when compared to the reference group. Staining of the biopsies with monoclonal antibodies revealed an increased total number as well as a number of activated eosinophilic granulocytes in specimens from adhesions and sactosalpinx compared to specimens from normal fimbriae. The findings indicate that eosinophilic granulocytes may have a possible role in the fibrotic process of pelvic adhesion disease. PMID- 7982728 TI - Dynamics of avian inflammatory response to Salmonella-immune lymphokines. Changes in avian blood leukocyte populations. AB - Investigations in our laboratories have indicated that an increased resistance to SE organ infectivity in chicks was conferred by the immunoprophylactic administration of SE-immune lymphokines (SE-ILK). This resistance was associated with an increase in the lamina propria thickness due to a marked infiltration of inflammatory polymorphonuclear cells (PMNs). In the present study, we determined whether the hematological profile of SE-ILK-treated chicks might reflect changes that are associated with the protection against organ invasion by SE. As protection has been observed in previous studies within 24 h of SE-ILK administration, we evaluated alterations in the circulating leukocyte profile in 1-day-old Leghorn chicks during this time period. We also determined whether the alterations in the peripheral blood leukocytes correlated with the increased protection against SE organ invasion induced by the SE-ILK. Within 4 h after an intraperitoneal injection of SE-ILK and challenge with SE, the number of circulating leukocytes increased significantly (P < 0.05) from all of the other treatment groups. The number of circulating PMNs was found to account for more than 80% of the increase in the number of circulating leukocytes. Using correlation analysis, we found a strong association between the number of circulating PMNs and the protection induced by SE-ILK against SE organ invasion. These studies associate the expansion of the available pool of circulating PMNs and the expression of innate resistance to organ invasion by SE. PMID- 7982729 TI - Analgesic and antiinflammatory effects of dipyrone in rat adjuvant arthritis model. AB - Dipyrone, a pirazolone derivative, is a known analgesic drug with minor toxic effects associated with its administration. The aim of the present study was to determine the analgesic and antiinflammatory effects of dipyrone in a model of chronic inflammation (adjuvant-induced arthritis in rats). Hind-paw hyperalgesia was detected in arthritic rats from the 10th to the 16th day of observation. Edema development was maximum (twofold increase) at the 14th day of observation compared to control animals and reduced at the 16th day of observation. Dipyrone (1-50 mg/kg) dose-dependently reduced both hind-paw hyperalgesia and edema from arthritic rats. However, it was shown to be more potent as analgesic than antiinflammatory in the present model. In contrast, indomethacin (2 mg/kg) and dexamethasone (0.4 mg/kg) completely inhibited hind-paw hyperalgesia and edema development. Our results indicate that dipyrone reduced the hyperalgesia and edema in arthritic rats by a mechanism not involving release of prostaglandin like substances. The possibility of dipyrone inducing analgesia in arthritic rats through a peripheral action supports the use of dipyrone as an alternative choice drug for the treatment of pain associated with arthritislike diseases in selected cases. PMID- 7982730 TI - Modulation of endothelial cell permeability by lung carcinoma cells: a potential mechanism of malignant pleural effusion formation. AB - This study examined the hypothesis that tumor cells metastatic to the pleura secrete a soluble factor(s) that directly increases endothelial cell permeability. Nitrocellulose filters were endothelialized with bovine pulmonary artery endothelial cells and exposed to conditioned media from either human lung adenocarcinoma (Calu-3), human lung squamous cell carcinoma (SK-MES-1), or control media for 16 h. The diffusional permeability (Pd x 10(-5) cm/sec) to [14C]albumin was then determined for each monolayer with Ussing-type chambers. Both adenocarcinoma conditioned media (ACCM) and squamous cell carcinoma conditioned media (SCCM) caused a two- to threefold increase in endothelial monolayer permeability. The addition of indomethacin (10 micrograms/ml) blocked the observed permeability increase in ACCM but not in SCCM, suggesting that the increase in permeability by ACCM was secondary to the production of prostaglandins. To confirm this, a variety of prostanoids previously shown to be produced by the Calu-3 cell line were added directly to the endothelial monolayer. Prostaglandin F2 alpha (PGF2 alpha) in both low (10 ng/ml) and high (100 ng/ml) concentrations for 16 h resulted in a three- to fourfold increase in permeability. Prostaglandin E2 (PGE2) resulted in a small increase in [14C]albumin permeability but only at high concentrations (100 ng/ml). PGF2 alpha production by the two tumor cell lines was measured using radioimmunoassay. Baseline adenocarcinoma production of PGF2 alpha was 117.5 pmol/10(6) cells and fell to 24.2 pmol/10(6) cells hours following incubation with indomethacin. The decrease in PGF2 alpha occurred in parallel with the changes in permeability. Concomitant, reversible changes in cell shape and F-actin distribution were detected in endothelial cells exposed to ACCM. No significant production of PGF2 alpha by the squamous cell carcinoma cell line was detected. These results suggest that both adenocarcinoma and squamous cell carcinoma secrete a soluble factor(s) that directly increases endothelial cell permeability to albumin and that in the case of adenocarcinoma this soluble factor may be a prostanoid such as PGF2 alpha. PMID- 7982731 TI - Impact of intravenous infusions of low and high doses of gamma globulins (IVIG) on phagocytic functions in adults with primary humoral immunodeficiency. AB - Twelve adult patients with primary humoral immunodeficiency were treated for at least six months with IVIG 200 mg/kg/mo and then crossed over to a high dose of 600 mg/kg/mo. Polymorphonuclear and mononuclear cells of these patients were tested after the third infusion in the low-dose cycle and then after the third infusion in the high-dose cycle, each time a day before, four days after, and 14 days after intravenous infusion. Each time, patients' cells and normal cells were tested using normal sera and patients' sera. IVIG infusions led to a significant increase in the level of circulating IgG, which was much more prominent in the high-dose group. Phagocytosis, phagocytic index, intracellular bactericidal activity and chemotaxis of polymorphonuclear cells (PMNs) were at least as active as in healthy controls. Actually in both cycles patients' PMN's had slightly higher phagocytic activity than normal cells. Patients' serum in the high dose cycle supported chemotaxis better than normal serum. Efficient phagocytic activity was maintained throughout the cycle; however, it was more active (P < 0.0125) in the midcycle in the high-dose cycle. Superoxide generation was normal in all conditions. Monocytic function was also normal in all conditions tested. It may be concluded that as far as cellular phagocytic functions are concerned, the high dose of IVIG does not protect the host more efficiently than the low dose. PMID- 7982732 TI - Migratory activity of blood polymorphonuclear leukocytes during juvenile rheumatoid arthritis, demonstrated with a new whole-blood membrane filter assay. AB - Polymorphonuclear leukocyte (PMN) migration is measured in whole blood in a migration chamber consisting of a membrane filter (3-microns pores, 140 microns thick) with an integrated chemoattractant depot (FMLP in solid form) attached to a plastic container. Control chambers lack FMLP (blanks). One test unit requires 300 microliters blood. Numbers and distribution of the PMN immigrants into the filters are determined microscopically. Altogether 26 measurements of PMN migration in five juvenile rheumatoid arthritis (JRA) patients with varying disease activity were compared with the reactions of a healthy control group (N = 32). Correlations were calculated with conventional laboratory parameters (WBC, PLT, BSR, CRP, Hgb, serum Fe) and disease activity. In comparison with healthy controls, PMNs of JRA patients generally show a markedly increased penetration depth into the filters irrespective the presence of the chemoattractant or the disease activity. Increased migratory reactions to FMLP in comparison to blanks were found during high disease activity only. The PMN penetration depth correlates positively with the CRP, and reciprocally with the Hgb blood levels. The migration assay combines fast and simple processing with good preservation of the genuine PMN activation state. PMID- 7982733 TI - Intergenerational communication: evaluations and analyses of talk exchanged between older adults and younger adults. AB - This special journal issue focuses on potential barriers and facilitators of successful intergenerational encounters. Communication Accommodation Theory has provided a useful and broad-based conceptual framework for understanding the nature of both appropriate and inappropriate modifications made in intergenerational communication. The first three articles concern the nature, eliciting conditions, and interpretations of patronizing speech. The last three articles shift from the manner of communication to an examination of the content of communication between young and older adults through discourse analysis. PMID- 7982734 TI - Patronizing the old: how do younger and older adults respond to baby talk in the nursing home? AB - To test the implications of Communication Accommodation Theory for intergenerational talk to dependent older persons, eighty young adults and seventy-one older adults evaluated speakers in a brief taped conversation. Specifically, the study was conducted to determine whether the apparent nurturant quality of the baby talk tone of voice and parental style would compensate for the lack of respect associated with this type of patronizing talk to elders. The talk was either secondary baby talk or a neutral variant addressed to an elderly resident in a nursing home by either a nurse or a volunteer. The caregivers who used baby talk were rated as significantly less respectful and competent than their peers in the neutral condition, but no differences were observed for nurturance of the caregiver. The recipients of baby talk were perceived to be less satisfied with the interaction. These findings were true for both caregiver roles and both respondent age groups. PMID- 7982735 TI - Patronizing the young: forms and evaluations. AB - Exploratory work indicated that Californian undergraduates were frequently, and irritatingly, patronized by older adults in a variety of ways. In a follow-up, using multidimensional scaling procedures, three distinct clusters representing young adults' own conceptions of patronizing speech emerged ("non-listening," "disapproving," and "parental"). In the main study, young adults were provided with a single vignette of a short conversation between an older and younger person. Eight versions of this vignette were devised independently varying elder's age (40- vs. 70-years) and speech style (neutral vs. non-listening vs. disapproving vs. parental). Participants were required to evaluate both vignette targets. As expected, the patronizing elders were negatively perceived. An evaluative hierarchy differentiated between the three patronizing forms, and in ways that differed depending on the nature of the judgmental task. Content analyses of open-ended data also revealed interesting differences in interpretive responses to the various vignette conditions. PMID- 7982736 TI - Physiognomic cues to age and the activation of stereotypes of the elderly in interaction. AB - This article reports the results of a study on the relationship between physiognomic cues to age and the activation of positive versus negative stereotypes of elderly individuals in interaction. Predictions were based upon a model of the role of elderly stereotypes in interaction. One group of undergraduates sorted photographs of elderly adults into four age categories, fifty-five to sixty-four, sixty-five to seventy-four, seventy-five and older, and other. Those photographs that were placed in the same age category by two-thirds or more of the students were used as a pool for the second phase of the study. This process produced a set of twenty-four photographs, eight (4 male and 4 female) from each of the three elderly age groups. A second group of students paired these photographs with sets of traits describing ten stereotypes of elderly persons, some positive and some negative. Results indicated that, as predicted by the stereotype-communication model, participants associated the positive stereotypes of elderly individuals with young-old physiognomic characteristics, whereas they associated the negative ones with old-old physiognomy. The results also suggested that gender may be a component of some stereotypes, and that some physiognomic characteristics may be considered prototypical of particular stereotypes. These results illustrate the importance of passive nonverbal elements of the communication situation in the activation of stereotypes of elderly individuals in interaction. PMID- 7982737 TI - Getting to know you: how own age and other's age relate to self-disclosure. AB - In this study, we compared self-disclosures made in ten same-aged (young-young) and ten mixed-aged (young-old) conversational dyads. We developed a scoring scheme to code get-acquainted conversations on amount, type, valence, and intimacy of self-disclosure (S-Ds). Overall, young women produced more S-Ds with same-aged than with older partners. Young women devoted marginally fewer of their self-disclosures to statements about the past than did older women. Younger and older women's S-Ds about the present and the past were not significantly different in how negative, positive, or intimate they were. The intimacy and negativity of disclosures made by the dyad members were more closely correlated in young-young than in young-old dyads. Young participants' affective reports following the conversations did not differ as a function of partner age, but did correlate with aspects of their partners' self-disclosures. Findings offer a contrast to the stereotype that older adults dominate conversations with intimate, negative disclosures about the past. PMID- 7982738 TI - Shared stories of the grandparent-grandchild relationship. AB - This research examined the storytelling that oftentimes characterizes interaction between grandparent and grandchild. Close to 120 individuals (college students) audiotaped an interaction with one of their grandparents. They were asked to have their grandparent first "tell a story that captures the meaning of life" for them. In addition, the grandparent was asked to complete the phrase, "To me, life is like ." the students were asked to tell their grandparent "a story that captured the essence of their life at this time in their life." Students were divided into similar numbers of same and mixed sex grandparent-grandchild relationships. The audiotaped interactions were content analyzed. A major assumption of this investigation is that the story which each individual chooses to share with their relational partner reveals to some extent the definitional nature of their relationship. Results of the storysharing interaction across relations revealed some gender differences in the types of stories grandparents share with their grandchildren. The implications of the shared stories upon the relational dynamics of the grandparent-grandchild relationship are discussed. In addition, the metaphors used by the grandparents to describe life in the presence of their grandchildren are analyzed. PMID- 7982739 TI - "Old age doesn't come alone": discursive representations of health-in-aging in geriatric medicine. AB - Traditional approaches to identity across the lifespan have assumed that age itself and generational statuses and roles determine "who we can be." In contrast, a discursive perspective can show how, during interaction, we actively construct age-salient identities for ourselves and others through talk. Conversational processes of age-identity management are explored in a corpus of (United Kingdom) geriatric medical outpatient consultations. In diverse ways, doctors deny the age-relevance of medical troubles that their patients routinely endorse. PMID- 7982740 TI - President's invited lecture: playing at being Pasteur. PMID- 7982741 TI - The J. F. A. Sprent Prize of the Australian Society for Parasitology. Differences in the life cycles of two species of reptile tick: implications for species distributions. PMID- 7982742 TI - The role of molecular genetics in field studies on malaria parasites. AB - Molecular genetics is having an important impact on the study of genes in natural populations of malaria parasites. The polymerase chain reaction (PCR) is proving particularly valuable for identifying genes in parasites taken directly from their hosts, without the need to establish them in culture. This is leading to novel methods of diagnosis, for example of drug-resistant parasites. Molecular techniques are also greatly assisting understanding of the genetic structure of parasite populations. This is relevant to the current debate on whether Plasmodium falciparum has a clonal or randomly interbreeding structure. Many patients are infected with mixtures of genetically distinct clones. PCR is being used to examine the genotypes of individual oocysts in the mosquito vector. In wild-caught mosquitoes in areas highly endemic for P. falciparum, a large proportion of oocysts are heterozygous, showing that cross-mating occurs frequently between clones during mosquito feeds. In areas of lower endemicity, there is evidence of less frequent crossing. PMID- 7982743 TI - The chromatin of trypanosomes. AB - The nuclear chromatin of trypanosomes is organised in the form of nucleosome filaments. When soluble chromatin is prepared under suitable conditions, a regular array of nucleosomes can be shown by electron microscopy. Chromatin of blood stream as well as procyclic culture forms of Trypanosoma brucei brucei and of T. cruzi shows limited compaction at salt concentrations increasing from 1 to 100 mM. No 30 nm fibres, typical for higher eukaryotes, are formed. Digestion of the nuclear chromatin with micrococcal nuclease and analysis of the histone proteins with various techniques reveal that the basic organisation of the trypanosome chromatin is similar but not identical as compared to that of higher eukaryotes. Distinct differences are present with respect to biochemical properties of the histones as well as to their interaction with the DNA. The primary structure of the histones also differs significantly from that found in other lower and higher eukaryotes. The function of the recently described H1-like proteins in trypanosomes is currently being investigated. The differences that have already been found in the structure and compaction of the trypanosome chromatin compared to that of higher eukaryotes lead us to expect differences of gene expression which, in turn, might offer targets for the control of trypanosomiasis. PMID- 7982744 TI - Genetic variation in parasitic nematodes and its implications. AB - An absolute pre-requisite for a genetic response to a selective pressure is genetic variation within the population under selection. Helminth populations are clearly able to respond to selective pressures and must, therefore, be genetically heterogeneous. While not quite tautological, this is at best indirect evidence for the existence of genetic variation but there are few examples of well documented helminth phenotypic variation with a proven genetic basis. Isozyme analysis has provided more direct evidence for variation but attempts to link this variation to responses to selection or to identify the forces maintaining that variation have been largely unsuccessful. Thus there is a clear need for new techniques. The recent application of PCR and direct sequencing technology to the study of helminth genetics has allowed the genotypes of individual worms to be determined and the first direct measurements of allele frequencies to be made in this group of organisms. In addition, the application of genetic and molecular data from Caenorhabditis elegans is a potentially rich source of new markers. These techniques do not require that the genetic basis of the phenotype in question be known since a large number of loci can be examined and selection detected through changes in the frequency of anonymous linked marker loci. Phenotypes with complex genetic bases can, therefore, be analysed. I have applied these techniques to the study of anthelmintic resistance genetics and others have applied them to the genetics of inhibited development in Ostertagia. Other phenotypes that are of great interest are the potential for selection of resistance to vaccination and the use of genetically resistant hosts. The ease with which helminths have countered all classes of anthelminitics and the apparently high levels of polymorphism in helminth populations suggest that immunological control methods may also prove to be vulnerable to the adaptive capabilities of the parasite. Evidence from a mouse-helminth model system has already provided evidence that worms can meet the challenge. PMID- 7982745 TI - Parasite-associated morbidity: liver fluke infection and bile duct cancer in northeast Thailand. AB - Infection with the liver fluke, Opisthorchis viverrini, remains a major public health problem in Northeast Thailand, where approximately one-third of the population is infected. The northeast region is largely populated by Laos descendent Thais who enjoy eating raw fish, which harbour the infective stage of the fluke. The parasite has maintained its presence in the population despite the widespread use of praziquantel and dissemination of health education material throughout the region by vigorous government-sponsored programs in recent years. The most severe consequence of liver fluke infection is cholangiocarcinoma, i.e. cancer of the bile duct epithelium. Although mortality due to the parasites alone appears to be uncommon, cholangiocarcinoma arising as a result of infection is one of the leading causes of death in the region. This paper reviews the pathogenesis of infection and the geographic, hospital-based and community studies which demonstrate the close relationship between infection and cancer. In addition, data from the Cancer Registry of Khon Kaen, Northeast Thailand and population-based studies using ultrasonography to visualize early tumours which illuminate the very high frequency of the cancer among heavily infected individuals and communities are discussed. Finally, the paper will close with a brief commentary on the prospects for control of the parasite and its likely impact on the frequency of cancer given the current epidemiological situation of liver fluke infection. PMID- 7982746 TI - Tick ecology. AB - The availability and expediency of acaricides for the control of ticks, together with the development of vaccination procedures against tick-borne diseases as a matter of priority, initially preceded information gained from research on tick ecology. The establishment of acaricide resistance, the increasing cost of chemical control and the data on production loss as an integral part of tick infestation are factors which led to the incorporation of ecological principles into tick control. Continuing research on the life processes of ticks as well as on their interaction with hosts and the environment, initiated producer manipulation of acaricide application frequencies, habitat manipulation techniques and the use of host immunity which are important for the establishment of economically suitable strategies of tick control. The role of tick ecology in establishing these concepts and its influence on current tick research is examined. PMID- 7982747 TI - Ecology and diversity of digenean trematodes of reef and inshore fishes of Queensland. AB - coral reefs harbour an extraordinary, concentrated diversity of life. What are the implications of this for parasites? After the corals themselves, the most striking component of coral reefs is the fishes. Individual coral reefs may harbour as many as a thousand species of fishes. Like most fishes, those of coral reefs bear remarkable loads of parasites. Records of digenean trematodes from 214 species of fishes from the Great Barrier Reef and 103 species of fishes from inshore Australian waters are compared to examine the ecological expression of parasite diversity on coral reefs. Coral reef fish had an overall prevalence of infection of 70% compared with 48% for their inshore counterparts and averaged 2.61 species of digenean per host species as compared with only 1.41 for the inshore group. A total of 236 species of Digenea has been collected from reef fishes. Most of the digeneans are concentrated in just a few families. Host specificity of digeneans of reef fishes is variable but, on average, each species infects 2.37 host species. Characteristics of the fauna studied so far are used to predict that the 1300 fishes of the Australian Great Barrier Reef are likely to harbour some 2270 species of Digenea. PMID- 7982748 TI - Expression and analysis of the diagnostic value of an Echinococcus granulosus antigen gene clone. AB - A pool of 9 sera from Echinococcus granulosus infected patients (PSP) was used to screen an E. granulosus cDNA library constructed in the expression vector lambda gt11. Ten reactive phage clones were isolated and 8 were confirmed in spot-lysis arrays probed with PSP. The insert of 1 of these clones (lambda AgEg4) previously characterized as an E. granulosus cytosolic malate dehydrogenase encoding gene was subcloned into the plasmid vector pGEX-1 and expressed as a fusion with glutathione S-transferase. The fusion peptide (Ag4-GST) was produced in Escherichia coli and its antigenicity was confirmed in colony immunoassay and in immunoblot using nondenaturing conditions. The lack of antigenicity of Ag4-GST in immunoblot using denaturing conditions suggests that the recognized epitopes are conformational. Ag4-GST was purified by affinity chromatography and tested in ELISA and immunodots to access its sensitivity and specificity in the diagnosis of human cystic hydatid disease. An overall sensitivity of 53.6% was obtained. Cross-reactions were observed with some sera from patients infected with Schistosoma mansoni and Wuchereria bancrofti. Ag4-GST was not recognized by any of the sera from Taenia solium infected patients tested. These preliminary results suggest that Ag4-GST could be useful as an accessory antigen to discriminate some cross-reactions with sera from cysticercosis patients, especially in regions like southern Brazil, where schistosomiasis and filariasis are not prevalent. PMID- 7982749 TI - The heritability and specificity of responsiveness to infection with Haemonchus contortus in sheep. AB - High responder (HR) and low responder (LR) lines of sheep of the Hungarian Merino breed were selected by using faecal egg counts (epg) as parameter of responsiveness after double artificial Haemonchus contortus test infections. A total of 81 lambs born to assortative matings of HR rams with HR ewes and LR rams with LR ewes, as well as 28 control lambs from unselected parent sheep, were studied to estimate the heritability of responsiveness. A relatively high level of heritability (h2 = 0.49 +/- 0.17) was observed. A comparative assessment of responder classification carried out by two subsequent and distinct H. contortus and Trichostrongylus colubriformis infections revealed a remarkable degree of agreement: identical results in 69.7% and marginal differences in 23.2% of 99 animals. These results suggest that by selecting sheep for high responsiveness to a certain species of nematodes, one can also achieve a substantial improvement of resistance against a wide range of other nematode species. PMID- 7982750 TI - Quantity of sporocysts and seasonality of two Rhipidocotyle species (Digenea: Bucephalidae) in Anodonta piscinalis (Mollusca: Bivalvia). AB - The prevalence of Rhipidocotyle campanula in Lake Kuivasjarvi, northern Finland, was 5.7% (n = 1486) during 1989. The prevalences of R. campanula and R. fennica in Lake Saravesi, central Finland, during 1987 to 1989 were 1.0 and 33.2% (n = 1157), respectively. No clear seasonality in prevalence was found in either species, although miracidia of these digeneans are present only in late summer and autumn. The proportion of infected clams in which the gonad was full of sporocyst tubules was on average 90% for R. campanula and 30% for R. fennica. Clams with only few sporocyst tubules in their gonad were observed most frequently in spring. Old; empty sporocyst ribbons of R. fennica first appeared in the clams during August after the beginning of the cercarial emergence and disappeared slowly thereafter. However, in both species viable sporocyst ribbons with early developmental stages of cercariae were found throughout the year. The emergence of R. fennica cercariae began during July and continued throughout September in Lake Saravesi. The duration of cercariae emergence was found to be up to 72 days in the laboratory. R. campanula cerariae in the northern Lake Kuivasjarvi emerged from mid-June until mid-August. PMID- 7982751 TI - Comparative ultrastructure of the cuticle of trichostrongyle nematodes. AB - The ultrastructure of the cuticle was examined in Austrostrongylus victoriensis, Patricialina birdi and Woolleya monodelphis (Herpetostrongylidae) from marsupials, Paraustrostrongylus ratti (Herpetostrongylidae) from rodents, Nippostrongylus magnus and Odilia bainae (Heligmonellidae) from rodents, Cooperia oncophora and Camelostrongylus mentulatus (Trichostrongylidae) from ruminants, and Nematodirus spathiger (Molineidae) from ruminants. The principal cuticular layers described previously were present in all species investigated. Major differences in the shape and composition of cuticular struts were observed as well as differences in components of the median zone of the cuticle, including the fluid-filled regions present in several species. Several different types of strut were observed. Although strut structure within the Heligmonellidae appeared to be constant, there were variations within both the Herpetostrongylidae and Trichostrongylidae. In Nem. spathiger the cuticular ridges lacked struts. The diversity of structures found in the species examined suggests that more extensive comparative studies of the trichostrongyle cuticle are warranted. PMID- 7982752 TI - An ultrastructural, cytochemical and freeze-fracture study of the surface structures of Brugia malayi microfilariae. AB - Ultrastructural analysis of the cuticle of Brugia malayi microfilariae indicated that it is composed of 2 regions: the inner one 15-20 nm thick with a homogeneous aspect and the outer one, designated as epicuticle, which is 15-20 nm thick. Three laminae separated by electron-lucent regions were seen in the epicuticle. Labeling of the cuticle and epicuticle of B. malayi and Wuchereria bancrofti microfilariae was observed when thin sections of Lowicryl-embedded parasites were incubated in the presence of gold-labeled phospholipase-C. Replicas of freeze fractured microfilariae showed the presence of 2 fracture planes in the epicuticle and no fracture plane in the inner region of the cuticle. The P face of the epicuticle outer fracture plane presented few particles similar to intramembranous particles (IMPs). The epicuticle inner fracture plane P and E faces presented large numbers of densely-packed small particles and many protuberances. Also, fracture faces of hypodermal and muscle cell plasma membranes were analyzed. Faces P and E of fractured membranes showed the presence of typical IMPs. P faces of both membranes showed larger amounts of particles than E faces. Fracture of muscle plasma membrane revealed a linear array of particles disposed in parallel rows on its P face. PMID- 7982753 TI - Monoclonal antibody-based immunohistochemical demonstration of Entamoeba histolytica in liver tissues of experimentally infected hamster (Mesocricetus auratus). AB - Histopathological changes and the presence of Entamoeba histolytica trophozoites was sequentially followed after intrahepatic inoculation of the parasites in 42 hamsters, 35 of which received no treatment whereas the remaining seven were treated with metronidazole. The liver tissues were examined for amoebic trophozoites by a monoclonal antibody (mAb)-based immunofluorescence assay (IFA), a mAb-based immunoperoxidase (IPx) and H & E staining. The number of hamsters developing abscesses was increased with time and was highest on day 30. Cellular infiltration with inflammatory cells and glycogen depletion were observed as early as day 5, followed thereafter by more intense inflammation of portal canals, periportal fibrosis, bile duct proliferation and hepatocyte degeneration. In 7 metronidazole-treated hamsters, no obvious pathological damage was seen. In a group of seven hamsters each, both IPx and IFA were positive in 3, 3, 4, 5 and 4 hamsters and in 3, 4, 3, 3 and 5 hamsters on days 5, 10, 15, 20 and 30, respectively. In 18 control hamsters, IPx, IFA and H & E were all negative. If the result from H & E was used as a gold standard, agreement between H & E and IFA and H & E and IPx were 91.4%, and 88.6%, respectively. Sensitivity and specificity were 93.8% and 89.5%, respectively for IFA, and 93.8% and 84.2%, respectively for IPx. PMID- 7982754 TI - Conformational characteristics of asparaginyl residues in proteins. AB - Backbone conformations at 1064 asparaginyl residues in 123 non-homologous, high resolution X-ray structures of proteins were analysed. Asn adopts conformations in left-handed alpha-helical region and other partially allowed regions in the Ramachandran map more readily than any other non-glycyl residue. Asn conformational clusters in the (phi, psi) regions of left-handed alpha-helix right-handed alpha-helix and extended (beta) strands were investigated in detail for their occurrence in various secondary structures, especially in beta-turn regions. Preferences were observed for Asn conformations in different positions in various beta-turn types, including the first and fourth positions of the turn. Asparaginyl residues with extended conformations are found to occur frequently in irregular regions, although they are expected to occur predominantly in extended strands or in the third position of type II beta-turns. Asn conformations at the N-cap positions of helices strongly prefer extended conformation than alpha L, which seems to be characteristic of non-glycyl residues at that position. In the liners connecting two extended strands and those connecting an alpha-helix and an extended strand, Asn with alpha L or alpha R conformation is more favoured than Asn with the beta-conformation. Analysis of Asn-Asn doublets and Asn-X-Asn triplets permitted identification of conformational families in such sequences. Results of this investigation provide useful hints in modelling Asn-rich regions in proteins such as malaria parasite coat protein. PMID- 7982755 TI - Peptide synthesis catalyzed by the Glu/Asp-specific endopeptidase. Influence of the ester leaving group of the acyl donor on yield and catalytic efficiency. AB - We recently described a two-step enzymatic semisynthesis of the superpotent analog of human growth hormone releasing factor, [desNH2Tyr1,D-Ala2,Ala15]-GRF(1 29)-NH2 (4), from the precursor, [Ala15,29]-GRF(4-29)-OH (1). C-Terminal amidation of 1 to form [Ala15]-GRF(4-29)-NH2 (2) was achieved by carboxypeptidase Y-catalyzed exchange of Ala29-OH for Arg-NH2. The target analog 4 was then obtained by acylation of segment 2 with desNH2Tyr-D-Ala-Asp(OH)-OR (3) (R = CH3CH2- or 4-NO2C6H4CH2-) catalyzed by the V8 protease. In this paper we report on the use of the recently isolated Glu/Asp-specific endopeptidase (GSE) from Bacillus licheniformis, which is shown to be an efficient catalyst for the segment condensation of 2 and 3. GSE is more stable than the V8 protease under the conditions employed (20% DMF, pH 8.2, 37 degrees C). The extent of conversion of 2 into 4 is limited by proteolyses at Asp3-Ala4 and Asp25-Ile26. However, this proteolysis is virtually eliminated by use of the appropriate ester leaving group, R. A systematic study of the kinetics of the GSE-catalyzed segment condensations of 2 and a series of tripeptide esters, desNH2Tyr-D-Ala-Asp(OH)-OR (3) [R = CH3CH2- (3a), CH3- (3b), ClCH2CH2- (3c), C6H5CH2- (3d), 4-NO2C6H4CH2- (3e)] revealed that rate of aminolysis versus proteolysis, and hence the conversion of 2 into 4, increase with increasing specificity (Vmax/Km) of GSE for the tripeptide ester.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7982756 TI - Bony fish neurophysins. Identification of MSEL- and VLDV-neurophysins of the pollack (Pollachius virens). AB - The two types of neurophysins known in vertebrate species, namely MSEL neurophysin (vasopressin-like hormone-associated neurophysin) and VLDV neurophysin (oxytocin-like hormone-associated neurophysin) have been purified from the pollack (Pollachius virens) pituitary through a combination of molecular sieving and high-pressure liquid chromatography (HPLC). Homogeneity has been checked by gel electrophoresis and return in HPLC. The apparent molecular masses measured by SDS-electrophoresis are near 12 kDa, significantly higher than those found for their mammalian homologues (10 kDa). The two types of neurophysins have been recognized through their N-terminal amino acid sequences. The primary structure of MSEL-neurophysin has been partially determined using automated Edman degradation applied on native and reduced-alkylated protein, as well as peptides derived by trypsin or staphylococcal proteinase hydrolyses. Comparison of pollack MSEL-neurophysin with ox, goose and frog counterparts reveals that particular positions in the polypeptide chain are subjected to substitutions and that the numbers of substitutions do not seem closely related to the paleontological times of divergence between the different vertebrate classes. PMID- 7982757 TI - 2,4-Dimethyl-5(4H)-oxazolone as reagent for activation and coupling of N substituted aspartic acid. AB - Reaction of the title oxazolone with N-benzyloxycarbonyl-L-aspartic acid in dichloromethane followed by addition of phenylalanine methyl ester.HCl and N methylmorpholine gave a 90% yield of a mixture of alpha- and beta-isomers of Z aspartylphenylalanine methyl esters in a 7:3 ratio. Reaction of the oxazolone with N-acetyl-L-aspartic acid anhydride gave a 75% yield of crystalline N-acetyl L-aspartic acid anhydride. tert-Butoxycarbonylaspartic and Z-glutamic acids also underwent activation to give the anhydrides. PMID- 7982758 TI - Structure-activity analysis of the antitumor and hemolytic properties of the amphiphilic alpha-helical peptide, C18G. AB - The in vitro antitumor and hemolytic activities of analogs of peptide C18G were compared in order to elucidate important structural features which affect cytotoxicity. The sequence of C18G, a basic peptide which can form an amphiphilic alpha-helix, is a derivative of the carboxyl terminus of human platelet factor IV. The results demonstrate that both amphiphilicity and helicity are essential for peptide activity, and that addition of a negatively charged amino acid results in decreased cell lysis. Whereas peptides exhibiting various degrees of potency did not differ with respect to helical content, an increase in peptide hydrophobicity did correlate with an increase in antitumor and hemolytic activity, as well as susceptibility to inhibition by serum. Higher hydrophobicity could be associated with improved ability to insert into the cell membrane. The position or context of specific residues within an amphiphilic peptide can also be important for activity. Furthermore, an increase in tumoricidal activity is not always accompanied by an increase in hemolytic activity or susceptibility to inhibition by serum. Possible reasons for the lower sensitivity of RBCs versus tumor cells to peptide cytotoxicity are discussed. Finally, compared with structurally idealized amphiphilic alpha-helical peptides, non-idealized peptides can possess higher tumoricidal activity, but are less hemolytic and less susceptible to serum inhibition. PMID- 7982759 TI - The rational design of highly stable, amphiphilic helical peptides. AB - A computer algorithm was devised for the evaluation of helical stability of potentially amphiphilic peptide sequences of specified length containing a set number of leucines in the hydrophobic region. All possible combinations of Glu, Lys and Gln in the hydrophilic region are rated using a set of empirical rules for salt bridge formation in alpha-helices, and the sequences which rate the highest are displayed. The rules for salt bridge formation were largely derived from published studies on the effects of salt bridges on helical stability. The algorithm was tested by redesigning a known amphiphilic alpha-helical peptide, alpha 1B or 1, which has been shown to aggregate into four-helix bundles. Comparison of the circular dichroism spectra of two peptides, 2 and 3, to 1 demonstrated that the redesigned peptide with the highest priority score from the algorithm, 2, was more helical when aggregated and slightly more helical as a monomer, whereas the peptide with the low priority score, 3, was somewhat less helical when aggregated and much less helical when monomeric. These results support the design of the algorithm, although conclusions based on aggregation data are complicated by the importance of interhelix contacts in the bundle. Further studies are underway to examine the reliability of the algorithm's predictions regarding the design of other helical peptides. PMID- 7982760 TI - Multiple peptide synthesis on acid-labile handle derivatized polyethylene supports. AB - Using the multipin peptide synthesis approach, a range of peptides with native amide and carboxylate C-termini were generated using an acid-labile approach. Polyethylene crowns grafted with hydroxyethylmethacrylate (HEMA) polymer were functionalized with either 4-hydroxymethylphenoxyacetic acid for the generation of peptide-carboxylate or p-[(R,S)-alpha-[1-(9H-fluoren-9-yl)methoxyformamido] 2,4-dim ethoxy- benzyl]phenoxyacetic acid for peptide-amide. A range of known peptide hormone sequences and other peptides with native C-termini were assembled by sequential incorporation of N alpha-Fmoc protected amino acids. Peptides were sidechain deprotected and cleaved from crowns with TFA/scavengers within 2 mL centrifuge tubes, and isolated by a series of ether/petrol wash and centrifugation steps. In this way it was possible to avoid a cleavage and isolation botteneck, allowing rapid processing of large numbers of peptides. PMID- 7982761 TI - Preparation and evaluation of peptidic aspartyl hemiacetals as reversible inhibitors of interleukin-1 beta converting enzyme (ICE). AB - Aspartyl aldehyde, Ac-Tyr-Val-Ala-Asp-H 1 (L-709,049), has been reported to be a potent, reversible inhibitor of interleukin-1 beta converting enzyme (ICE) [Thornberry, N.A. et al. (1992) Nature (London) 356, 768-774]. In the context of our own work, we have developed a general synthetic approach to peptidic aspartyl aldehydes. Semicarbazone derivative, H-Asp(Ot-Bu)-Sc 4, was identified as a stable, masked aspartyl aldehyde equivalent. We have used 4 to synthesize a series of mono-, di- and tripeptide aldehydes, and multigram quantities of Ac-Tyr Val-Ala-Asp-H 1, Ac-Tyr-Val-Lys-Asp-Sc 21 and Ac-Tyr-Val-Lys-Asp-H 2. Biological evaluation of these aspartyl aldehydes and derivatives suggests that the tripeptide scaffold, Z-Val-Ala-Asp, is a peptide scaffold that retains good potency and selectivity for ICE. PMID- 7982762 TI - Solid-phase peptide synthesis and biological activity of bovine thymopoietin II (bTP-II). AB - Bovine thymopoietin (bTP), a 49 amino acid polypeptide, was synthesized using Merrifield's solid-phase peptide synthesis methodology. The polypeptide was purified using anion-exchange chromatography and reversed-phase HPLC and characterized by mass spectrometry and amino acid analysis of the full-length peptide and of products derived from digestion with Staphylococcus aureus V8 protease. The biological activity of the synthesized product was tested in several assay systems. Synthetic bTP was found to induce the expression of Thy 1.2 antigen on T-lymphocytes from athymic mice, in agreement with previous studies on the biological activity of endogenous bTP. Biological activity at skeletal muscle and neuronal nicotinic acetylcholine receptor sites, as reported by others for bTP, could not be confirmed in our studies. The absence of biological activity at nicotinic receptor sites may be related to the results of a recent report demonstrating the presence of a cobratoxin-like molecule in preparations of natural bTP. These data indicate that synthetic peptides have an important role for the evaluation of the specificity of the biological activity of polypeptides. PMID- 7982763 TI - Crystal structure of deltakephalin: a delta-selective opioid peptide with a novel beta-bend-like conformation. AB - The solid-state structure of deltakephalin (Tyr-DThr-Gly-Phe-Leu-Thr) has been determined by single-crystal X-ray diffraction. Deltakephalin (DTLET) is a synthetic opioid peptide which differs from enkephalin in that a D-Thr has been substituted for Gly2 and a sixth residue, L-Thr, has been added. Clear colorless plates obtained using vapor diffusion and macro-seeding crystallization techniques were monoclinic; space group C2 with a = 27.389(5), b = 9.205(2), c = 16.788(2) A, beta = 98.87(2) degrees and V = 4181.4(14) A3. The asymmetric unit contained one molecule of DTLET and six molecules of water, giving a calculated density of 1.28 g cm-3. The crystal structure revealed that DTLET has a pseudo type I' beta-bend which is stabilized by an intramolecular side-chain to backbone hydrogen bond. This is the first reported observation of a pseudo beta-bend conformation in a solid-state structure of an enkephalin analog. PMID- 7982764 TI - Anorectal functional deficit in the Brown Bowel syndrome. AB - The Brown Bowel Syndrome is characterised by degeneration and pigmentation of large bowel mucosa. We present a report of this unusual syndrome in which, for the first time, a functional deficit, reflected in a reduced internal and sphincter tone, is documented. This abnormality was reversed following sub-total colectomy and vitamin E therapy. PMID- 7982765 TI - Is a random urinary albumin concentration a useful screening test in insulin treated diabetic patients? AB - The debate continues on how to screen for microalbuminuria in clinical practice in patients with insulin-dependent diabetes mellitus. Our study assesses the value of a spot morning urine specimen obtained at a clinic visit. In 1984, as part of a randomised survey of our diabetes clinic, 43 of 249 patients with insulin treated diabetes mellitus, were found to have microalbuminuria (urinary albumin concentration 35-300 ug ml-1) on a spot morning urine sample. These subjects were compared with an age-matched control group from the 1984 cohort who did not have microalbuminuria. Eight years later, in the group with microalbuminuria, 10 had died compared to six in the control group (p = 0.17) with 62.5% of all deaths being from cardiovascular disease. In the group with microalbuminuria, 10 of 27 still had incipient nephropathy while five had progressed to nephropathy. In the group without microalbuminuria only three of 33 patients had progressed to microalbuminuria while none had progressed to nephropathy. In conclusion a spot morning urine sample is a useful screening test to identify patients at risk of progression to nephropathy. PMID- 7982767 TI - Overview of research in the medical sciences in Israel: institutions, investigators and funding. PMID- 7982766 TI - Hernia of the lung: case report and literature review. AB - Hernia of the lung is an uncommonly encountered clinical entity. The majority of reported hernias are acquired traumatic thoracic hernias. A case report of an acquired spontaneous lung hernia is presented. A literature review of the classification, diagnosis, treatment and current incidence is discussed. PMID- 7982768 TI - A 10 year survey on Mycobacterium tuberculosis isolates in Israel and their drug resistance. AB - An increased incidence of tuberculosis has been observed in Israel in 1985, 1986 and since 1990--years of large waves of immigrations. A very similar trend of disease was observed in the Mycobacterium Reference Laboratory of Israel, and consequently a survey was undertaken among the 1,181 bacteriologically confirmed tuberculosis cases newly registered there in 1983-92. The overall percent distribution of drug-resistant Mycobacterium tuberculosis during this period was 12.6% (7.3% resistant to one drug and 5.3% (multiple drug resistance). The highest percent distribution of drug-resistant bacilli was found among immigrants from the former Soviet Union (37.3%) and Ethiopia (16.2%). The highest incidence of disease was found in males and in patients aged > 30. Pulmonary disease was the most common form for all patients: among the extrapulmonary cases, the most frequently involved site was the genitourinary system in Israelis and the lymph nodes in Ethiopians. Most isolates fit into one variant by biochemical analysis, indicating the need for a more sensitive method to type M. tuberculosis for epidemiological purposes. The data included in this survey provide information useful for a national tuberculosis program. PMID- 7982769 TI - Physiological and neuropsychological effects of theophylline in chronic obstructive pulmonary disease. AB - The effect of oral theophylline on clinical course, exercise, neuropsychological performance and bronchial reactivity was studied in chronic airflow obstruction. Twelve patients with chronic obstructive pulmonary disease (COPD) [mean age 62.4 +/- 1.6 years (SE), and forced expiratory volume in 1 sec of 1.15 +/- 0.1 l] were randomized to 4 weeks treatment with oral theophylline followed by 4 weeks of placebo, in a double-blind fashion. During each period, patients underwent clinical evaluation, incremental exercise, a battery of neuropsychological tests measuring a wide range of cognitive functions, and an inhaled methacholine provocation. On the active drug (levels 9.5 +/- 1 mg/l), vital capacity and maximal breathing capacity were 16 +/- 7% and 20 +/- 7% respectively, higher relative to placebo (P < 0.04). Exercise capacity, as reflected by peak O2 uptake and the anaerobic threshold, improved 14 +/- 5% and 18 +/- 5% (P < 0.04). In contrast, bronchial responsiveness to inhaled methacholine and the mean scores on the neuropsychological tests were not significantly altered by the drug. Clinical symptoms were unaltered, but mild side effects were more common on theophylline. We concluded that in moderate to severe COPD, theophylline treatment, at the low range of the therapeutic dose, improves lung function and exercise capacity. This improvement is achieved with no detectable alteration of bronchial reactivity to methacholine and with no deleterious effect on cognitive functions. PMID- 7982770 TI - Interventional neurology: botulinum toxin as a potent symptomatic treatment in neurology. AB - Local injections of botulinum toxin is a well-accepted treatment for focal dystonias, hemifacial spasms and strabismus. Its use by skilled neurologists has been reported to be safe and effective. We report our experience with botulinum toxin injections in 108 patients with various central nervous system disorders. Botox was effective in upper face dystonia (86% improvement), spastic dysphonia (92% improvement), platysma muscle spasms and spasmodic torticollis (range of movement 61%, pain and tension 90%). It was also very effective in a few patients with apraxia of eyelid opening, parkinsonian jaw tremor, teeth clenching, palatal myoclonus and adductor leg spasticity. No serious side effects were recorded. Botulinum toxin is a useful symptomatic treatment for many neurological disorders, and one of the leading mode of treatments in the new subspecialty in neurology called "Interventional neurology." PMID- 7982771 TI - Transvaginal Doppler sonography for detecting ectopic pregnancy: is it really necessary. AB - In this prospective study we compared transvaginal duplex Doppler ultrasound with two-dimensional imaging for the diagnosis or exclusion of ectopic pregnancies. The study group comprised 76 stable patients with serum beta-human chorionic gonadotropin (hCG) levels > 100 mIU/ml in whom ectopic pregnancy was clinically suspected. Ectopic pregnancies were verified in 42 patients (60%), intrauterine pregnancies (normal and abnormal) in 19 (27%), and possible complete abortions, either intrauterine or extrauterine, in 9 patients (13%). Based on 2-D imaging alone, the appearance of an adnexal mass separated from the ovaries, and a lack of clear intrauterine gestational sac indicated ectopic pregnancy with a sensitivity of 95%. Intrauterine sac-like structures and absence of adnexal masses excluded ectopic pregnancies with a specificity of 89%. High velocity systolic flow, and low impedance diastolic flow which characterizes trophoblastic tissue when detected outside the uterus, had a sensitivity of 48%, while the presence of trophoblastic signals in the uterus or their absence outside the uterus excluded ectopic pregnancies with a specificity of 89%. The positive predictive values were 91% for Doppler and 95% for 2-D imaging, while the negative predictive values were 89% for imaging alone and 44% for Doppler. These data suggest that transvaginal Doppler ultrasound has significant lower sensitivity and negative predictive value and does not provide more useful diagnostic information than 2-D imaging alone for stable patients with suspected ectopic pregnancies. PMID- 7982772 TI - Clinical and laboratory evaluation of 40 patients with Sheehan's syndrome. AB - Forty patients with typical obstetric history of Sheehan's syndrome were reviewed retrospectively. Together with baseline laboratory values, insulin hypoglycemia test was evaluated in 15 patients, thyrotropin-releasing hormone (TRH) in 27 and luteinizing hormone-releasing hormone (LH-RH) in 7 patients. Baseline hormone values suggested secondary hypothyroidism, hypogonadotropic hypogonadism and hypocortisolemia. According to the results of the anterior pituitary stimulation tests, one patient (6.6%) showed normal cortisol response and one patient (6.6%) showed normal growth hormone response to hypoglycemia. Nine patients (33.3%) who were clinically and biochemically hypothyroid demonstrated adequate TSH response to TRH. None of the patients showed normal prolactin response to TRH. Four out of seven amenorrheic patients (57.1%) had adequate follicle-stimulating hormone and/or LH responses to LH-RH. It has been concluded that isolated anterior pituitary hormone deficiencies may occur in patients with Sheehan's syndrome. Prolactin response to TRH seems the most sensitive screening test for detecting Sheehan's syndrome in patients with typical obstetric history. PMID- 7982773 TI - Total proctocolectomy, pancreaticoduodenectomy and total gastrectomy for multiple carcinomas in a patient with familial adenomatous polyposis. AB - A unique case of familial adenomatous polyposis presenting with simultaneous adenocarcinoma of the periampullary region, gallbladder and several gastric lesions, 10 years after a total proctocolectomy, is reported. Multiple gastrointestinal carcinomas associated with familial polyposis have been reported sporadically. However, this is the only known patient who successfully underwent a pancreaticoduodenectomy (Whipple procedure) and a total gastrectomy in addition to a previous total proctocolectomy. PMID- 7982774 TI - Rapid method for detection of cytomegalovirus in shell vials cell culture compared with conventional tubes cell culture and detection of IgM antibodies. PMID- 7982776 TI - Symptomatic heterotopic pancreas of the stomach. PMID- 7982775 TI - Bacterial lymphadenitis complicating chronic lymphatic leukemia. PMID- 7982777 TI - Control of malaria by drug-mediated iron deprivation. PMID- 7982778 TI - Graduating medical residents: will they be ethical, wise, strong, rich and honorable? PMID- 7982779 TI - Nisoldipine for hypertension. PMID- 7982780 TI - Use of the APACHE II severity score in an Israeli GICU. PMID- 7982781 TI - Local malaria transmission in Israel. PMID- 7982782 TI - Organophosphate poisoning and necrotizing pancreatitis. PMID- 7982783 TI - Talmudic aphorisms on diet IV fasting--the lightest diet! PMID- 7982784 TI - Julius Axelrod, Bernard Katz and Ulf von Euler--Nobel Prize winners for the discovery of mechanisms of nerve signal transmission. PMID- 7982785 TI - Jack Gross, l921-l994. PMID- 7982787 TI - Effects of irradiation on neuropeptide expression in rat salivary gland and spinal cord. AB - It is well-known that a large number of factors can influence the expression of neuropeptides in the nervous system. In the present study, the effects of unilateral and bilateral irradiation to the rat head and neck on the expression of neuropeptides in the innervation of the submandibular gland and in the ganglionic cells of the submandibular ganglion was examined ten days and six months after treatment. Antisera directed against enkephalin and bombesin and immunohistochemical methods were used. The effects of bilateral irradiation on the staining pattern of various neuropeptides in the cervical spinal cord were also studied. In the submandibular gland and in the submandibular ganglionic cells, there was a markedly increased neuropeptide expression ten days after bilateral treatment, as seen after staining with both antisera used, while no changes occurred after unilateral treatment. Six months after treatment, the pattern of neuropeptide expression in the submandibular gland/ganglion corresponded to that seen in controls. Irradiation did not lead to any changes in the staining pattern of neuropeptides in the spinal cord. The observations show that there is a great complexity in the susceptibility of nervous tissues to radiotherapy with respect to influences on the expression of neuropeptides. PMID- 7982786 TI - Distribution patterns of the paraneuronal endocrine cells in the skin, gills and the airways of fishes as determined by immunohistochemical and histological methods. AB - The neuro-endocrine cells of fish skin and respiratory surfaces, and their bioactive secretion as far as is known, are reviewed, and compared with similar elements in tetrapods, particularly amphibians. In the skin of teleost fish, immunohistochemistry has shown that Merkel cells react for serotonin, neuron specific enolase and enkephalins. The pharmacology is not established in dipnoans or lampreys. In some teleosts, neuromasts react for substance P and leu enkephalins; substance P is also reported from some ampullary organs (electroreceptors). Taste buds of teleosts may react for enkephalin and substance P. Basal cells of taste buds react for serotonin and neuron-specific enolase. Some unicellular skin glands of teleosts express bioactive compounds, including serotonin and some peptides; this ectopic expression is paralleled in amphibian skin glands. The dipnoan Protopterus has innervated pulmonary neuro-endocrine cells in the pneumatic duct region with dense-cored vesicles. In Polypterus and Amia the lungs have serotonin-positive neuro-endocrine cells that are apparently not innervated. In fish gills, a closed type of neuro-endocrine cell reacts for serotonin, an open type for enkephalins and some calcium-binding proteins (calbindin, calmodulin and S-100 protein). The functions of neuro-endocrine cells in fishes await investigation, but it is assumed they are regulatory. PMID- 7982788 TI - Immunocytochemical detection of Ca(2+)-dependent subspecies of protein kinase C in mouse embryos before and during compaction. AB - To confirm the possibility that protein kinase C is involved in compaction of mouse embryos, the presence and distribution pattern of Ca(2+)-dependent subspecies of this enzyme in mouse embryos, before and during compaction, were examined immunocytochemically with three different monoclonal antibodies. These were MC-1a, MC-2a and MC-3a, which selectively interact with the subspecies of the enzyme known as types I, II and III, respectively. Only when embryos were incubated with MC-3a, was immunofluorescence clearly detected in all cells of embryos before and during compaction. This result demonstrates the presence of type III protein kinase C in embryos before and during compaction and suggests the possibility that the type III enzyme may be involved in compaction. No marked differences were found in the distribution pattern of the type III enzyme between embryos examined before and during compaction. PMID- 7982789 TI - The production and characterization of a new monoclonal antibody to the trefoil peptide human spasmolytic polypeptide. AB - Human spasmolytic polypeptide (hSP) is a member of the growing family of trefoil peptides which are expressed in discrete regions of the body, most notably the gastrointestinal tract. Much of the research into the localization of the spasmolytic polypeptide has relied on hybridization in situ to detect its mRNA, due to the absence of a suitable antibody. The aim of the present study was to develop and characterize a monoclonal antibody against the human spasmolytic polypeptide, using a combination of immunohistochemistry and hybridization in situ. After immunoblotting, the antibody detected a 14 kDa protein in gastrointestinal tissue extracts from the stomach and small intestine only. Using immunohistochemistry, human spasmolytic polypeptide showed a distinctive staining pattern in the duodenum which co-localized with its mRNA. The co-localization of the immunoreactive peptide with its mRNA provides good evidence that the antibody truly recognized human spasmolytic polypeptide. PMID- 7982790 TI - Localization of [D-Ala2]deltorphin I-like immunoreactivity in perinatal rat respiratory system. AB - The localization of [D-Ala2]deltorphin I, a delta-opioid receptor ligand, was studied in the lower respiratory tract of developing rats using an immunohistochemical method. [D-Ala2]-like immunoreactive cells were detected first in the principal bronchus as early as embryonic day 16. As embryos grew, positive cells became gradually visible everywhere from principal bronchi to respiratory bronchioles. The density of positive cells reached the highest level on embryonic day 21, but decreased gradually after birth. Positive cells were no longer seen on postnatal day 30 in any region of the airways. No positive cells were ever found in the trachea or alveoli of rats at any age studied. Ultrastructural examination indicated that the immunoreactive cells possessed a similar morphology to serous or Clara cells of the respiratory epithelium. Immunoreaction products tended to locate at the apical cytoplasm of positive cells. The results suggests that [D-Ala2]-like molecule(s) may be expressed transiently in serous cells or Clara cells, or both, of the rat bronchopulmonary tract. Such a molecule may act as a pulmonary growth-promoting or a differentiation-initiating factor in an early period of lung development. PMID- 7982793 TI - Love, desire and infatuation: encountering the erotic spirit. AB - Erotic love is a universal experience with all the features of numinous archetypal experience. Indeed, for many people it may be their closest brush with the divine. Prior to Plato the spiritual and sexual aspects of the erotic spirit seem to have been fused but Plato introduced a distinction between physical and sexual love that opened up a conflict between them that has not yet been healed. It is proposed that love is an experience of the imagination; links are drawn between this idea and Plato's ladder of love in which the love of beauty and truth supercedes physical love. At the same time, the indissoluble linkage between the sexual and the spiritual is asserted, especially as found in the poetry of Donne. In addition to the regressive elements emphasized in psychoanalytic views of love, encountering the erotic spirit involves an initiation process culminating in the transformation brought about through the painful loss of love's illusions. PMID- 7982792 TI - Histochemical analysis of glycoproteins in the unicellar glands in the epidermis of an Indian freshwater fish Mastacembelus pancalus (Hamilton). AB - The unicellular glands in the epidermis of the Indian freshwater fish Mastacembelus pancalus consist of three types of mucous cells and sacciform cells. The histochemical properties of their secretory glycoproteins have been analysed by means of a battery of histochemical methods. These included methods for the identification and simultaneous visualization of oxidizable vicinal diols, O-acyl sugars, O-sulphate esters and sialic acid residues with or without side-chain O-acyl variants. Four general classes of glycoproteins (GPs) were identified. These included (i) GPs with O-sulphate esters and oxidizable vicinal diols, (ii) GPs with oxidizable vicinal diols and sialic acid residues with or without O-acyl substitution at C7, (iii) GPs mainly with O-sulphate esters, low moieties of GPs with oxidizable vicinal diols, O-acyl sugars and sialic acid residues with side-chain O-acyl variant predominantly at C8 (or which are di- or tri-substituted) or C9 and in traces of sialic acid residues without O-acyl substitution or with O-acyl substitution at C7, and (iv) GPs with traces of oxidizable vicinal diols, O-acyl sugars and sialic acid residues with O-acyl substitution at C8 (or which are di- or tri-substituted) or C9. The physiological significances of these GP classes and their release on the surface of the epidermis are discussed with special reference to their role in lubrication, protection and inhibition of the invasion and proliferation of pathogenic microorganisms in the epidermis, as adapted to the peculiar mode of life of the fish. PMID- 7982791 TI - Immunohistochemical localization of blood-retinal barrier breakdown sites associated with post-surgical macular oedema. AB - Post-surgical macular oedema results from blood-retinal barrier breakdown, but it is not accompanied by structural abnormalities in the retinal vessels or retinal pigmented epithelium. Previous studies, using horseradish peroxidase in a primate model, suggested that leakage occurs primarily through this epithelium. This study was conducted to localize sites of the barrier breakdown in humans following different types of intra-ocular surgery and to compare them with eyes affected with ocular inflammatory disease, ocular infection, and choroidal melanoma. Paraffin sections of eyes were immunohistochemically stained for albumin to localize extravascular albumin, which was graded in a masked study. With aphakia/pseudophakia, penetrating keratoplasty, ocular inflammatory disease, ocular infection, and choroidal melanoma, barrier breakdown occurred primarily at the inner blood-retinal barrier (retinal vasculature), but leakage also occurred at the outer barrier (retinal pigmented epithelium). After retinal re-attachment surgery, the inner and outer blood-retinal barriers were equally compromised. Vascular leakage in the optic nerve head coincided with barrier failure in these disorders. The widespread pattern of blood-retinal barrier compromise with leakage at multiple sites suggests that soluble mediators are likely to play a role in postsurgical macular oedema, ocular inflammatory disease, and choroidal melanoma. PMID- 7982794 TI - Is FSH required for adult spermatogenesis? PMID- 7982795 TI - An orthotopic model for the study of growth factors in the ventral prostate of the rat: effects of epidermal growth factor and basic fibroblast growth factor. AB - In order to determine if epidermal growth factor (EGF) or basic fibroblast growth factor (bFGF) are capable of stimulating prostatic growth in situ, we complexed EGF and bFGF to a Matrigel (MG) vehicle that was subsequently injected orthotopically into the ventral prostate of adult rats. Three weeks following a single injection of 0.1 ng of EGF or bFGF, the wet weight of the growth factor injected lobes of the ventral prostate was increased (P < or = 0.025) 144 +/- 14% and 138 +/- 8%, respectively compared to contralateral lobes injected with MG only. Total DNA and protein per lobe (P < or = 0.025) and the incorporation of bromodeoxyuridini (BrdUrd; P < or 0.01) were all significantly increased in lobes injected with EGF or bFGF compared to MG-injected lobes. Thus, EGF and bFGF were stimulating true growth of the rat ventral prostate in situ. The induced prostatic growth was ligand specific, because co-injection with neutralizing antibodies abolished EGF and bFGF stimulation of prostatic wet weight. The effect of a single injection of 0.1 ng of growth factor was long-lasting and elevated prostatic wet weight for 4 (P < or = 0.05; bFGF) to 6 (P < or = 0.05; EGF) weeks. Histologic evaluation did not reveal any gross changes in the ratio of stroma to epithelium in either EGF- or bFGF-injected lobes at the 0.1 ng/lobe dose. A slight hyperplasia of the prostatic epithelium was detected in lobes injected with 10 ng of EGF. Of note, the incorporation of BrdUrd was primarily localized in the luminal and basal epithelial cells, whereas incorporation into the prostatic stroma was scanty in lobes injected with either EGF or bFGF. In summary, we have developed an orthotopic model enabling the study of the roles of growth factors in prostatic physiology, function, and disease in situ. Additionally, we have demonstrated that when injected orthotopically into the rat ventral prostate, EGF and bFGF stimulate the growth of the prostatic epithelium to similar degrees. PMID- 7982796 TI - Effect of finasteride on adrenal steroidogenesis in men. AB - Finasteride, a 5 alpha-reductase inhibitor, does not bind to the androgen receptor and has no other known hormonal activity. To determine what effect, if any, it has on adrenal steroidogenesis, 10 healthy men received 5 mg finasteride daily for 28 days. Adrenocorticotropic hormone (ACTH) stimulation tests were performed before and after 4 weeks of finasteride administration (5 mg daily). Serum levels of 17-hydroxypregnenolone, 17-hydroxyprogesterone, deoxycorticosterone, corticosterone, aldosterone, cortisol, dehydroepiandrosterone, and androstenedione were measured before and 60 minutes after i.v. ACTH. Finasteride decreased serum dihydrotestosterone levels from 31 +/- 5 to 4.4 +/- 1.2 ng/dl (P < 0.001). There were no significant changes in basal or ACTH-stimulated serum levels of adrenal steroids. There was also no significant decrease in the product to precursor ratio for the seven adrenal enzymes tested. Finasteride increased mean serum androstenedione levels by 17% (P = 0.10) and significantly increased the androstenedione to 17-hydroxyprogesterone ratio (P = 0.02 before ACTH and 0.05 after ACTH). These changes are most likely due to inhibition of androstenedione metabolism by 5 alpha-reductase. In conclusion, finasteride has no detectable effect on adrenal steroidogenesis, other than that which can be explained by inhibition of the 5 alpha-reductase enzyme. PMID- 7982797 TI - Acute immobilization stress disrupts testicular steroidogenesis in adult male rats by inhibiting the activities of 17 alpha-hydroxylase and 17,20-lyase without affecting the binding of LH/hCG receptors. AB - We have investigated the effect of acute immobilization (3 hours) stress on testicular steroidogenesis in the adult rat. Immobilization did not alter plasma luteizing hormone (LH) levels, but plasma testosterone (T) levels were reduced by 82%. Plasma levels of corticosterone in stressed rats were elevated more than ninefold over control levels. After 3 hours of stress, testicular levels of progesterone were elevated 33%, and levels of 17 alpha-hydroxyprogesterone and T were reduced 47% and 37%, respectively, compared to controls. Immobilization for 3 hours had no effect on the association or dissociation rate constants of LH/human chorionic gonadotropin (hCG) receptors of testicular interstitial cells and did not alter specific hCG binding. The effect of 3 hours of immobilization on testicular 17 alpha-hydroxylase and 17,20-lyase was assessed by incubating testicular microsomes from stressed and control animals in the presence of 21[14C]progesterone and [3H]17 alpha-hydroxyprogesterone. Immobilization of rats reduced the Vmax values of 17 alpha-hydroxylase and 17,20-lyase by 47% and 48%, respectively, but had no effect on the Km values. These results support the hypothesis that stress for 3 hours disrupts rat testicular steroidogenesis via a mechanism that is independent of changes in circulating levels of LH and the binding characteristics of LH/hCG receptors. The effects of immobilization on the content of testicular steroids and on the activities of 17 alpha-hydroxylase and 17,20-lyase suggest that stress inhibits the activities of both 17 alpha hydroxylase and 17,20-lyase. PMID- 7982798 TI - Tunica vaginalis sperm reservoir in a monkey model of vas deferens obstruction. AB - Repeat microscopic epididymal sperm aspiration (MESA) is used to treat congenital absence of the vas deferens (CAVD). Use of alloplastic implants as reservoirs results in poor sperm motility and pregnancy rates. An autoplastic tunica vaginalis reservoir for epididymal sperm has been used in four patients, with one resultant pregnancy. We studied this technique in a monkey model. Eight reservoirs were created in four monkeys (Cercopithecus aethiops). The vas deferens was ligated close to the epididymis. A transverse incision was made in the caput epididymis, and sperm were aspirated for analysis. Cut margins of the epididymal duct were sutured open to the visceral layer of the tunica vaginalis. The defect in the parietal layer of the tunica vaginalis was repaired, and sterile Tyrode's solution was instilled in the potential space between the parietal and visceral layers. Initial epididymal sperm obtained at the creation of the sperm reservoir demonstrated adequate mean motility (60.5%, grade 1.5), morphology (82.8% normal), and viability by Eosin-Y exclusion (69.9%). At 4 weeks, no reservoirs were palpable. Percutaneous aspiration (25-gauge angiocatheter) yielded no fluid. Surgical exposure of the reservoirs demonstrated significant adhesions and scar formation between the parietal and visceral layers of the tunica vaginalis, obliterating the potential space. No sperm were detected in irrigant fluids at this time. In conclusion, adhesion and scar formation may prevent use of the tunica vaginalis reservoir as an alternative to repeat MESA in treatment of CAVD. PMID- 7982799 TI - Long-term alterations in the permeability of the blood-testis barrier following a single intratesticular injection of dilute aqueous glycerol. AB - The mechanism whereby glycerol exerts its antispermatogenic action is not known. The objective of this study was to determine, with the use of [3H]inulin and [125I]albumin by in vivo and in vitro methods, whether glycerol exerts its effect by altering the permeability of the blood-testis barrier (BTB). Adult male rats received a single intratesticular injection of either glycerol (10% or 20%; treated) or saline (control), and 2, 4, 8, 26, and 56 weeks after treatment, either [3H]inulin or [125I]albumin was administered either by infusion or directly to the testicular tissues. Radioactivity was measured in testicular tissue, rete testis fluid, and seminiferous tubular fluid. Following in vivo administration, the uptake of [3H]inulin by seminiferous tubules, rete testis fluid, and seminiferous tubule fluid was significantly greater in the treated than in the control testes at all times after treatment. Radiolabeled inulin, injected into isolated testes or added to medium in which isolated tubules were incubated, accumulated at significantly higher levels in the seminiferous tubule compartment of treated than control tissues. Rete testis fluid from treated testes, collected by micropuncture following efferent duct ligation, contained about 5- to 13-fold more radioactivity than fluid from controls. Following infusion of 50 microCi of [125I]albumin into the jugular vein, the accumulated radioactivity was significantly greater in testicular and epididymal tissues and in the seminiferous tubule fluid from treated than from control animals. In all experiments the significant differences between treated and control were maintained during the period of 2-56 weeks following glycerol treatment.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7982800 TI - The ethane dimethanesulfonate-induced decrease in the fertilizing ability of cauda epididymal sperm is independent of the testis. AB - Several decades ago it was reported that when adult male rats were exposed to a single injection of 50 mg/kg body weight ethane dimethanesulfonate (EDS) and mated with untreated females, average litter size was significantly reduced as early as 2 weeks later. Recently, we demonstrated that EDS exerts multiple effects in the epididymis of adult rats. Some of these effects were independent of reduced serum testosterone (T) levels. Later we found that EDS has direct effects on epididymal epithelial cells in vitro. Herein, we sought to determine whether EDS perturbs the fertilizing ability of cauda epididymal sperm. Four days after exposure to 50 mg/kg EDS, sperm from the proximal cauda epididymidis were inseminated into adult receptive females in utero; on the next day the percentage of fertilized eggs was determined. Exogenous T administration and castration were used to determine what role, if any, androgen deprivation and the testis had on the fertilizing ability of proximal cauda epididymal sperm. Sperm motion parameters, serum T, T in the caput/corpus epididymidis, and detergent-extracted sperm protein were evaluated and correlated with fertilizing ability. We found that both castration and EDS exposure significantly compromised the fertilizing ability of sperm in proximal cauda epididymidis 4 days after exposure. Exogenous T, sufficient to maintain serum T, completely restored the fertilizing ability of sperm following castration, but not after EDS exposure. Moreover, exogenous T failed to restore fertilizing ability when castrated animals were exposed to EDS. Thus, the effects that EDS exerts on sperm maturation in vivo are independent of the testis. Finally, the only endpoint that was well correlated with fertilizing ability was the relative amount of an acidic 18-kDa sperm protein. PMID- 7982801 TI - Effect of follicular or oviductal fluids on movement characteristics of bovine sperm during capacitation in vitro. AB - Mammalian sperm exhibit characteristic motility changes associated with capacitation. Movement characteristics of bovine sperm incubated in noncapacitating (control, medium alone), capacitating (oviduct fluid, nonluteal, and luteal), or capacitating, acrosome reaction inducing (follicular fluid) conditions were investigated using a computer-assisted automated semen analysis system. Sperm were incubated up to 4 hours in a modified Tyrode's medium (control), 20 and 60% nonluteal (NL) or luteal (L) oviduct fluid (ODF), or 20 and 60% follicular fluid (FF). Relative to sperm incubated in control medium, motility of sperm treated with ODF or FF had increased linearity and vigorous motility. Sperm incubated in 60% ODF or FF showed a small decrease in mean trajectory/path straightness and velocity over time compared to 20% fluid treatments and control. Frequency distribution graphs were symmetric for 20% NL- and L-ODF treated sperm. However, 20% FF and 60% ODF and FF treatments had distributions skewed to the left, indicating smaller values for lateral head displacement (ALH) and curvilinear velocity (VCL). Median values for ALH and VCL were determined for control-treated sperm, and subtracted from individual sperm values for all treatments to estimate deviation from control, designated ALHc and VCLc. Three-dimensional plots of ALHc, VCLc and corresponding frequency indicated shifts in peak patterns for fluid-treated sperm compared to control sperm. Incubation in 20% ODF and FF resulted in peak shift for ALH and VCL values; yet, little change in peak position was observed in sperm incubated in 60% ODF and FF.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7982802 TI - A morphometric comparison of the nuclear morphology of fresh and frozen-thawed human zona-bound and unbound sperm. AB - The role of sperm nuclear morphology in zona binding and the effect of cryopreservation on sperm nuclear morphology have been investigated using objective criteria. The nuclear dimensions of fresh and frozen-thawed sperm heads that had been prepared by the swim-up (SU) technique, and bound to human oocytes in vitro, were measured using a computer-assisted image analyzer. These were compared with each other and also to sperm in the SU samples and those that had not bound to the zona pellucida. The unbound (UB) sperm and SU sperm had very similar nuclear morphology. In contrast, the nuclear morphology of the zona-bound (ZB) sperm differed significantly (P < 0.05) from that of the SU and UB sperm. These differences were found specifically between area, breadth, and roundness in the SU and ZB sperm preparations, and between area and roundness in the UB and ZB sperm preparations; the ZB sperm had smaller but rounder nuclei than either the SU or UB sperm. In addition, the frozen-thawed sperm in the SU and UB groups showed a trend towards smaller nuclei than the corresponding fresh groups, whereas the frozen-thawed ZB sperm had significantly (P < 0.05) smaller nuclear dimensions than the fresh ZB sperm. From the present study it appears that the ZB sperm are a morphologically distinct population, although it is not yet clear whether these differences reflect functional events that occur in the sperm head during its maturation or changes at the level of the sperm's DNA after the initial stage of zona binding.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7982803 TI - Leukocytic infiltration into the human ejaculate and its association with semen quality, oxidative stress, and sperm function. AB - Immunocytochemical techniques have been used to monitor the size and composition of the leukocyte population in unfractionated human semen samples and sperm populations generated by Percoll gradient centrifugation. The characteristics of the leukocyte population have then been related to the quality of the semen profile, the production of reactive oxygen species, and the functional competence of the spermatozoa. A majority (97%) of the ejaculates examined contained leukocytes, and in 82.4% the major cell type was the granulocyte. Small numbers of T cells, B cells, and monocytes/macrophages could also be found in 62%, 43%, and 21% of samples, respectively, and patients were occasionally identified in whom one of these cell types became the predominant leukocyte species. Although a subpopulation of patients was identified in whom the infiltration of multiple leukocyte species was positively correlated with the concentrations of spermatozoa and precursor germ cells in semen, in general, the presence of leukocytes, to the point of leukocytospermia, did not significantly influence any component of the semen profile. Similarly, the fertilizing potential of the washed spermatozoa, as assessed by in vitro tests of the acrosome reaction and sperm-oocyte fusion, was not correlated with the concentration of seminal leukocytes. In contrast, the carryover of leukocytes into the washed sperm preparations profoundly influenced the fertilizing potential of the spermatozoa via mechanisms that were associated with the production of reactive oxygen species. These results have implications for the diagnostic significance of leukocyte contamination in the context of male infertility and assisted conception. PMID- 7982804 TI - Lipid peroxidation and antioxidant enzyme activities in the rat testis after cigarette smoke inhalation or administration of polychlorinated biphenyls or polychlorinated naphthalenes. AB - Lipid peroxidation products and antioxidant enzyme activities were studied in the rat testis following exposures to cigarette smoke, polychlorinated biphenyls (PCBs), or polychlorinated naphthalenes (PCNs). Three hours after a single 1-hour period of smoke inhalation, the levels of fluorescent chromolipids and thiobarbituric acid-reactive species (TBARS) were markedly increased in the testis (+49%, P < 0.01, and +43%, P < 0.05, respectively). Twelve hours after daily smoking for 1 hour, for 1, 5, or 10 days, such an increase was not found. Activities of the antioxidant enzymes superoxide dismutase (SOD), catalase, glutathione peroxidase (GSH-Px), glutathione transferase (GSH-Tr), or hexose monophosphate shunt (HMS) were not affected immediately, 3 hours, or 12 hours after a single smoking session. Twelve hours after smoking for 5 days, the activity of catalase was decreased (-16%, P < 0.05). Smoking exposures had no consistent effects on serum follicle-stimulating hormone (FSH), luteinizing hormone (LH), or testosterone concentrations. Single i.p. injections of PCB or PCN mixtures resulted in decreases in testicular SOD activity 1 day after the exposures (-14%, P < 0.05, and -51%, P < 0.01, respectively). Catalase activity also decreased after both exposures (-30 to -42%, P < 0.05, at days 1-7 after PCB exposure, and -37 to -43%, P < 0.05, at days 3-7 after PCN exposure). Ninety days after the PCN exposure, activities of GSH-Px and GSH-Tr were decreased in the testis (-20%, P < 0.05, and -26%, P < 0.05, respectively).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7982805 TI - Development of computer-directed methods for the identification of hyperactivated motion using motion patterns developed by rabbit sperm during incubation under capacitation conditions. AB - Rabbit spermatozoa developed motions that mimicked hyperactivated motility during incubation for 16-20 hours under capacitation conditions and in several other commonly used media. Sperm from some rabbits failed to acquire this type of motility, and sperm from others failed to survive the long incubation time. Four motility patterns developed during incubation for 16-20 hours. Motility parameters measured by the CellSoft and CellTrak motion analysis systems were similar except for the average amplitude of lateral head displacement. Multivariate discriminant analysis with complementary regression analysis, and an unrelated tree structured classification method (CART), were used to derive rules, based on motility parameters, for the objective classification of sperm into the two motility classes: 1) nonhyperactivated motility and 2) hyperactivated motility or motility that mimicked hyperactivated motility. The motility parameter wobble (WOB) as superior to the commonly used parameter, linearity, as a classifier of motility types. It classified sperm into the two motility groups with 96.6% efficiency and, together with curvilinear velocity (VCL), attained classification efficiencies of 98%. The classification model produced by CART was preferred over the one obtained by discriminant analysis. The rule for motility classification was dependent on the motion analysis system used to measure the motion parameters. The rule for the CellSoft system, WOB < or = 0.78 and VCL > or = 51 microns/second, classified sperm with an efficiency of 98%, whereas the rule for the CellTrak system, WOB < or = 0.6 and VCL > or = 55 microns/second, achieved a classification efficiency of 97%. These rules should facilitate the study of sperm hyperactivation and its role in sperm function. PMID- 7982806 TI - Responses of inferior colliculus neurons in C57BL/6J mice with and without sensorineural hearing loss: effects of changing the azimuthal location of an unmasked pure-tone stimulus. AB - Azimuth functions (discharge rates evoked by tone bursts as a function of stimulus azimuth) were obtained from neurons in the inferior colliculus (IC) of C57 mice aged 2, 7 and 12 months. Because of a gene that affects the cochlea, C57 mice exhibit high-frequency sensorineural hearing loss at 7 and 12 months. Azimuth functions were examined for differences that might be related to the decline in localization acuity that accompanies hearing loss in this strain. Irrespective of age group, nearly all neurons in the central area of the IC were sensitive to the azimuth of a best frequency (BF) stimulus, as revealed by azimuth functions in which firing rates varied by more than 50% from maximum to minimum at one or more intensities. The age groups were similar in many respects (e.g., there were no significant differences in the proportion of functions meeting the criterion for direction sensitivity, the proportion of neurons with direction sensitive functions over a range of intensities, azimuth function shapes, the locations or stability of 'borders' separating angles evoking high versus low discharge rates). However, in 7- and 12-month-olds: the proportion of IC neurons in which the strongest excitatory driving was evoked by ipsilateral stimulation was significantly larger; azimuth function borders were more likely to be 'reversed' (i.e., the high rates being evoked by the more ipsilateral angle); and a greater proportion of azimuth functions met the criterion for direction sensitivity only minimally. The findings suggest that binaural excitatory-inhibitory interactions are altered in IC neurons of hearing-impaired mice. PMID- 7982807 TI - Responses of inferior colliculus neurons in C57BL/6J mice with and without sensorineural hearing loss: effects of changing the azimuthal location of a continuous noise masker on responses to contralateral tones. AB - Extracellular recordings were obtained from inferior colliculus neurons of young adult (2-month-old) C57 mice with normal hearing and middle-aged (6-month-old) C57 mice with sensorineural hearing loss as they responded to best frequency (BF) tones (signal) in the presence of a continuous background noise (masker). Rate/level functions were obtained for the signal alone, noise bursts alone, and the signal in continuous noise as a function of masker location. For both groups of mice, thresholds for BF tones were significantly elevated in the presence of noise at all three noise locations. Separating the signal and masker sources significantly improved masked tone thresholds of 2-month-old mice but not hearing impaired mice. The decreased ability of middle-aged mice to benefit from separation of the signal and masker sources may reflect alterations in binaural processing as a result of sensorineural hearing loss. PMID- 7982808 TI - Enhancement of the auditory cortex evoked responses in awake guinea pigs after noise exposure. AB - In a previous paper [Popelar et al., Hear. Res. 26, 239-247 (1987)] we have shown that amplitudes of the auditory cortex evoked responses (AC-ER) in awake guinea pigs were enhanced for several hours after 1 h of noise exposure whereas amplitudes of the compound potential of the auditory nerve (CAP) and of the inferior colliculus evoked responses (IC-ER) declined. The present study demonstrates that the duration of the AC-ER amplitude increase is related to the intensity of the noise exposure (white noise, for 30 min or 1 h, intensity range 105-125 dB). The AC-ER amplitude as well as the threshold shift increased linearly with increasing intensity of the noise. The maximum AC-ER increase occurred when clicks served as stimuli; amplitude enhancement was smaller for 1 kHz tone pips and was absent when 20 kHz tone pips were used. The amplitude enhancement was specific for the auditory cortex since the amplitude of visually evoked responses, recorded in the occipital cortex, was unchanged after noise exposure. It is suggested that the postexposure amplitude enhancement of the AC ER is produced by temporary exhaustion of inhibitory processes in the auditory cortex. PMID- 7982809 TI - Pure-tone masking profiles for human auditory brainstem and middle latency responses to 500-Hz tones. AB - A simultaneous masking paradigm was used to determine the frequency selectivity of human auditory brainstem (ABR) and middle latency (MLR) responses to 60 dB pe SPL 500-Hz probe tones in 12 normal adults. Masking profiles for simultaneous recordings of the ABR and MLR were obtained in the presence of pure-tone maskers presented at 60- and 70-dB SPL. Results show sharp amplitude profiles with maximum reduction in amplitude seen using the 500-Hz maskers. There were no significant differences in the masking profiles for the ABR and MLR waves to the 500-Hz probe tones. An additional measure of frequency selectivity, bandwidth at 50% reduction in amplitude (W50), also demonstrated no significant difference between the ABR and MLR waves. In summary, the results of this study and those of an earlier study (Mackersie et al., 1993) suggest no significant difference in the frequency selectivity of the ABR and MLR to low-intensity (60 dB pe SPL) 500- and 2000-Hz tones. PMID- 7982810 TI - Mineralocorticoid type I receptor in the rat cochlea: mRNA identification by polymerase chain reaction (PCR) and in situ hybridization. AB - Expression of mineralocorticoid type I receptor (MR) gene in the rat cochlea was determined using molecular biological techniques. We synthesized complementary DNA (cDNA) from rat cochlear total RNA and then amplified MR cDNA fragments by polymerase chain reaction (PCR). The amplified cDNA fragments were subcloned into an expression vector and the nucleotide sequence was analyzed to confirm the expression of mRNA encoding MR in the cochlea. We then synthesized digoxigenin labeled riboprobes with this cloned DNA template and examined the localization of MR mRNA in the cochlea by in situ hybridization. The amino acid sequence of MR cDNA expressed in the cochlea was identical to that of the MR first cloned in the rat hippocampus. In situ hybridization showed the expression of MR mRNA in marginal cells of the stria vascularis, suggesting that aldosterone may regulate microhomeostasis of the endolymph, presumably by modulating Na, K-ATPase activity. Intense MR signal was also identified in spiral ganglion cells, the function of which remains to be determined. PMID- 7982811 TI - ATP antagonists cibacron blue, basilen blue and suramin alter sound-evoked responses of the cochlea and auditory nerve. AB - The P2-purinergic receptor antagonists suramin, cibacron blue and basilen blue, the latter two being isomers of reactive blue 2, were studied for their effects on sound-evoked responses from the cochlea (cochlear microphonic, CM; summating potential, SP; distortion product otoacoustic emissions, DPOAE) and auditory nerve (compound action potential, CAP). Local application of these compounds (10 1000 microM) into the cochlear perilymph was associated with concentration dependent response alterations. Effects of suramin on cochlear responses were minimal: High-intensity SP was reduced slightly at concentrations > or = 330 microM without significant alterations in CM or DPOAEs. The amplitude of the auditory nerve CAP was suppressed and its latency increased at drug concentrations > or = 100 microM. Cibacron blue and basilen blue were of greater potency in their effects on cochlear and auditory nerve responses. DPOAEs were generally reduced, low-intensity SP was reduced and high-intensity SP was increased and CM was little affected at drug concentrations 100-1000 microM. The CAP was suppressed and its latency increased at concentrations > or = 33 microM. Effects of suramin were largely reversible; those associated with cibacron blue and basilen blue generally were not. To the extent that these drugs acted selectively as antagonists of ATP receptor-mediated activity, results support the hypothesis that endogenous ATP exerts profound actions at the level of the cochlea and the auditory nerve. PMID- 7982812 TI - Trimethyltin disrupts N1 sensitivity, but has limited effects on the summating potential and cochlear microphonic. AB - Trimethyltin (TMT), a model neurotoxicant, has previously been demonstrated to disrupt auditory thresholds in laboratory subjects. In this experiment we characterized the potency of this ototoxicant by means of a dose response study and then evaluated the functional effects of TMT administration when tone-bursts were presented at supra-threshold levels. Guinea pigs were anaesthetized and prepared for electrophysiological measurement of the compound action potential (CAP) and cochlear microphonic (CM). Subsequently averaged wave forms generated by tone-bursts of 0-80 dB SPL were evaluated in order to calculate both a N1 and a summating potential (SP) input-output function. We show that TMT at doses as low as 0.2 mg/kg produce elevations in N1, but not in the CM isopotential curve. Using exposures to 0.5 mg/kg TMT we show a profound reduction in the slope of the N1 input-output curve, but no shift in the SP. The results are consistent with the hypothesis that TMT disrupts function at the synapse between the inner hair cell and the Type 1 spiral ganglion cell. PMID- 7982813 TI - Effects of stimulus level on nonspectral frequency discrimination by human subjects. AB - Frequency difference limens were determined as a function of reference-stimulus level for pulsatile electrical stimuli in 5 postlingually deaf human subjects with Nucleus-22 cochlear implants and for sinusoidally amplitude-modulated acoustic white noise stimuli in 4 normal-hearing humans. Subjects were tested at levels throughout the dynamic range and extending to the lowest detectable levels. Response stability was measured over the course of 10 sessions. For electrical stimulation in the deaf ears, difference limens decreased as a function of level throughout much or all of the dynamic range of hearing. This result contrasts with the case for nonspectral acoustic stimulation of normal hearing subjects, where nonspectral frequency difference limens were strongly affected by level only near the detection threshold. These data suggest differences in the acoustic and electrical response spaces that must be considered in the design of auditory prosthesis processors. PMID- 7982814 TI - Narrowband stimulation and synchronization of otoacoustic emissions. AB - Tone-burst-evoked otoacoustic emissions were obtained for several normal listeners with and without spontaneous otoacoustic emission using an optimized tone burst. The dependence of the response amplitude on stimulation level shows a linear increase below a certain value close to the threshold in quiet and levels off at higher levels exhibiting only small differences between non-linear and linear averaging modus. In addition, the latency of the response tends to decrease and the sharpness of the resonance decreases with increasing stimulation level. Synchronization tuning-curves were obtained using a fixed tone burst to elicit an evoked otoacoustic emission and a probe tone at different frequencies for synchronizing the SOAE. These synchronization tuning curves exhibit relatively sharp resonance characteristics (Q3 varying between 3 and 8) for subjects with spontaneous otoacoustic emissions and less sharp tuning (Q3 varying between 1 and 3) for subjects without spontaneous otoacoustic emissions. These experimental results could be reproduced very well with a model of a single non linear Van-der-Pol-oscillator with the appropriate parameters. The results indicate that spontaneous otoacoustic emissions and narrow-band-evoked otoacoustic emissions are generated by the same mechanism which can be modelled as a self-sustained oscillator. PMID- 7982815 TI - Nonlinear input-output functions derived from the responses of guinea-pig cochlear nerve fibres: variations with characteristic frequency. AB - Rate-versus-level functions (RLFs) were recorded from individual cochlear nerve fibres in anaesthetised guinea-pigs. Variations in the shapes of these functions with frequency were used to derive input-output (IO) relationships for the mechanical preprocessing mechanisms in the cochlea. It was assumed that these preprocessing mechanisms operated linearly at frequencies well below each fibre's characteristic frequency (CF). The IO functions derived at each fibre's CF provided strong evidence of compressively nonlinear preprocessing in most regions of the cochlea. However, the apparent degree of compression depended on the fibre's CF, and hence on the presumed site of cochlear innervation. For fibres with CFs of between 1.5 and 3.6 kHz, the CF derived IO functions grew at rates of around 0.5 dB/dB. For fibres with CFs above 4 kHz, the IO functions were more compressive, with high-intensity asymptotic slopes of around 0.13 dB/dB. In the highest (> or = 10 kHz) CF fibres, the degree of compression depended on the physiological condition of the cochlea; the derived IO functions becoming more linear as the cochlea became less sensitive. The derived IO technique was not well suited to analyse responses evoked by very low frequency (e.g., < 500 Hz) tones. Nonetheless, the CF RLFs from fibres with CFs lower than approximately 1 kHz provided little evidence of mechanical nonlinearity near the apex of the cochlea. These findings imply a longitudinal variation in the mechanisms of cochlear preprocessing, and provide important new tests for functional models of the cochlea. PMID- 7982816 TI - Development of contralateral suppression of the VIIIth nerve compound action potential (CAP) in the Mongolian gerbil. AB - We studied whether same-frequency contralateral tones of 65 dB pSPL (peak Sound Pressure Level) suppress the VIIIth nerve compound action potential (CAP) evoked by 40-45 dB pSPL tone pips in the Mongolian gerbil from 22 to 92 days after birth (DAB). The primary stimuli were tone pips of 1, 2, 4, 8, and 10 kHz; only the 1 kHz CAP amplitude was suppressed significantly by tones of the same frequency. The suppression was seen at 22 DAB, and underwent little relative change with development. PMID- 7982817 TI - Effect of interaural time differences on middle-latency and late auditory evoked magnetic fields. AB - To determine if interaural time differences (ITDs) in binaural stimuli affect the middle-latency auditory evoked fields (AEFs) in the same manner as they affect the N100m deflection, neuromagnetic responses were recorded over the whole head using a 122-channel SQUID magnetometer. Binaural stimuli were lateralized to three positions, left, midline, and right, on the basis of ITDs. The N100m was significantly larger to stimuli with contralaterally-leading ITDs than to stimuli with no, or with ipsilaterally-leading ITDs. Neither the P30m nor the P50m deflections of the middle-latency response were significantly affected by ITD, although the P30m showed a tendency, similar to but smaller than that of N100m, to be larger to stimuli with contralaterally-leading ITDs. In some subjects, the source location of the P50m was anterior and inferior to the sources of the P30m and N100m, which are generated in the superior surface of the temporal lobe. Sound-related muscular artifacts were seen in the posterior recording channels of one subject, and the contribution of this activity to the signals over the temporal area was determined. PMID- 7982818 TI - Lanoy N. Hazel, 1911-1992: a brief biography. PMID- 7982819 TI - Effects of beta-hydroxy-beta-methyl butyrate on performance and carcass quality of feedlot steers. AB - Beta-hydroxy-beta-methyl butyrate (HMB), a compound formed during catabolism of leucine, was fed to 256 crossbred steers as 0 or .03% of diet dry matter. Effects on performance, carcass characteristics, and tissue composition were measured. Groups of 32 steers per diet were slaughtered after 105, 119, 133, and 147 d on feed. The HMB was fed to each group only during the final 82 d they were fed. Averaged across slaughter date, animal performance was not altered by HMB; however, an interaction between HMB and time on feed was detected. Feeding HMB increased (P < .01) daily gain of steers slaughtered at 105 d but decreased (P < .01) daily gain of steers slaughtered at 147 d. Steers fed HMB had numerically higher marbling scores that resulted in a trend toward higher carcass quality grades. Steers receiving HMB tended to have less (P < .08) s.c. fat and fewer steers with yield grades of 4 or greater (1.6 vs 4.7%). Supplementation of HMB to feedlot steers tended to increase (P < .07) the ratio of intramuscular fat to subcutaneous fat. Steers fed HMB had higher (P < .001) blood plasma concentrations of HMB (3.06 vs 1.70 mg/L) and lower (P < .03) blood plasma concentrations of cholesterol (108.4 vs 118.7 mg/dL). Feeding HMB tended to increase (P < .10) lipid content of the longissimus muscles of those steers slaughtered at 105 d. PMID- 7982821 TI - Dietary energy source and density: effects of roughage source, roughage equivalent, tallow level, and steer type on feedlot performance and carcass characteristics. AB - The effects of roughage level (10, 20, or 30% roughage equivalent [RE]), roughage source (alfalfa vs cottonseed hulls), roughage regimen (constant RE vs 2% RE during the mid-finishing period), tallow level (1.2 vs 4.6%), and steer type (British crossbred [BRITX] vs Bos indicus crosses [BRX]) were evaluated in three experiments with a common allotment and several overlapping treatments. Steers (n = 432; initial weight = 326 +/- 26 kg) were divided into three BW blocks and allotted randomly to 72 pens and 24 treatments. Steers were fed steam-flaked, sorghum grain-based finishing diets for 124 to 166 d. Diets with 20% RE decreased gain efficiency and 30% RE diets decreased both gain (linear, P < .07) and efficiency (linear, P < .001) compared with 10% RE diets. Reducing roughage level during the mid-finishing period improved overall gain efficiency 2, 7, and 24% (P > .2, < .05, and < .001, respectively) for the 10, 20, and 30% RE diets, respectively. Steers fed cottonseed hulls consumed more feed (9.6 vs 8.8 kg/d, P < .001) but tended to gain less (1.53 vs 1.58 kg/d, P = .11) than steers fed alfalfa, were leaner, and had fewer carcasses grading Choice (62 vs 77%, P < .05). Feeding 4.6% tallow decreased DMI (P < .05) and improved gain efficiency (P < .05) compared with 1.2% tallow. The BRITX steers consumed more feed (6%, P < .001) but were somewhat less efficient (3.5%, P < .05) than BRX steers. Carcasses from BRITX steers tended to be fatter than carcasses from BRX steers and more of them graded Choice (62 vs 37%, P < .01). Commercial BRX steers did not perform as well as BRITX steers on higher-energy-density diets (4.6% tallow or variable roughage regimen). Knowledge of the genetic background of feeder cattle can be important in the selection of dietary energy density and marketing expectations. PMID- 7982820 TI - Effect of increasing the dietary level of rapeseed meal on intake by growing beef steers. AB - Three experiments were conducted to determine the effects of rapeseed meal on intake by cattle. In the first experiment, the effect of increasing rapeseed meal level on intake, growth, and performance of growing beef steers was evaluated. In the second experiment, the effect of extrusion (glucosinolate reduction) on supplement intake by steers was evaluated. In the third experiment, the effect of increasing dietary rapeseed meal level on supplement intake was evaluated. In the first experiment, rapeseed meal replaced soybean meal at 0, 33, 67, or 100% of the supplemental protein. Dry matter intake, crude protein intake, and serum thyroxine levels were decreased linearly (P < .01) with increasing level of rapeseed meal in the supplement. Protein sources used in Exp. 2 were soybean meal, rapeseed meal, extruded rapeseed meal, and soybean meal containing rapeseed oil at the same level as the rapeseed meal. In Exp. 3, the protein sources were composed of different combinations of rapeseed meal and soybean meal (100% rapeseed meal; 67% rapeseed meal and 33% soybean meal; 33% rapeseed meal and 67% soybean meal; and 100% soybean meal). Supplement intake was measured at .5, 4, and 24 h after feeding in both experiments. Extrusion treatment, which reduced glucosinolate content in rapeseed meal 75%, did not improve (P > .10) supplement intake. Rapeseed meal resulted in lower supplement intakes at .5 and 4 h than the soybean meal and soybean meal+rapeseed oil supplements (P = .003).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7982822 TI - Estimates of genetic parameters for 320-day pelvic measurements of males and females and calving ease of 2-year-old females. AB - Records from 12 breed groups collected from 1983 to 1991, included in the Germ Plasm Utilization project at the U.S. Meat Animal Research Center, were analyzed separately by breed group and combined to estimate heritabilities and genetic correlations for 320-d male and female pelvic width, height, and area, and for 320-d male pelvic and female 2-yr-old calving ease. Calving ease was analyzed as a trait of the dam using 1) actual and 2) binary scale calving ease scores with a covariate of calf birth weight. A bivariate animal model and derivative-free REML incorporating sparse matrix techniques were used. When breed groups were analyzed separately, heritability estimates of male and female 320-d pelvic traits varied by breed group and sex. Average genetic correlations between male and female 320 d pelvic width, pelvic height, and pelvic area were large and positive. When breed groups were combined (n = 26,071), heritability estimates for 320-d pelvic traits were moderate in size. Genetic correlations of .68, .48, and .61, between male and female 320-d pelvic width, height, and area, respectively, suggest male and female pelvic traits are largely under the same genetic control but are correlated traits rather than the same trait. Heritability estimates for actual calving ease in 2-yr-olds ranged from .00 to .49 in separate breed group analyses, and from .00 to .37 for binary measures. When breed groups were combined, heritability was .11 for actual calving ease and was .09 on the binary scale.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7982823 TI - A genetic study of estrus symptoms at puberty and their relationship to growth and leanness in gilts. AB - Puberty traits of 740 Yorkshire gilts from a selection experiment were analyzed. Heritabilities were estimated to be .32 for pubertal age, .23 for length of proestrus, .16 for length of standing estrus, .29 for ability to show standing reflex, and .24 for intensity of vulvar symptoms. Genetic correlations between length of proestrus, intensity of vulvar symptoms, and ability to show standing reflex were positive. There seemed to be a negative genetic correlation between percentage of lean and intensity of vulvar symptoms. There were negative genetic correlations between growth rate and length of standing estrus, and between growth rate and ability to show standing reflex. PMID- 7982824 TI - Prediction error variances for interbreed genetic evaluations. AB - A table for adjusting expected progeny differences (EPD) to a base year and breed basis depends on analyses of records of progeny of bulls of different breeds in a common environment and requires that those reference bulls also have other progeny to provide within-breed EPD. Currently, the germ plasm evaluation project at the Meat Animal Research Center (MARC) provides such a common environment for reference bulls of several breeds for estimation of breed differences for the reference sires. Reference sire estimates of breed differences are adjusted by the difference between average EPD of reference bulls and average EPD for the base year for that breed. Two related questions are as follows: 1) What are confidence ranges for the adjustments and 2) What are accuracies of interbreed EPD? Application of statistical principles and algebra shows that 1) apparent confidence ranges for breed adjustments are small, 2) apparent confidence ranges are substantially underestimated when random sire effects within breed are ignored, 3) correct confidence ranges also are small, 4) usual measures of accuracy cannot be applied to interbreed comparisons, and 5) standard errors of prediction used in calculating confidence ranges for interbreed comparisons are much less affected by variance of the adjustment factors than by within-breed accuracies for two bulls being compared except for bulls with accuracies of near unity. Alternatives of predicting differences between bulls of the same or different breeds or between a bull of any breed and an average bull of a base breed are discussed in terms of confidence ranges.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7982825 TI - Ten generations of selection for predicted weight of testes in swine: direct response and correlated response in body weight, backfat, age at puberty, and ovulation rate. AB - Selection for predicted weight of testes at 150 d of age (PWT) was practiced for 10 generations to determine the effect on reproductive and growth traits in swine. Mass selection among boars (line TS) or random selection (line C) was practiced beginning with the F3 generation of a Large White x Landrace composite population. Population size in each line was 40 to 45 litters by 15 sires per generation. Responses were estimated by regressions on cumulative selection differentials for PWT and on generation number and by mixed-model derivative-free REML procedures. The realized heritability of PWT was .35 +/- .02 and the response per generation was 19 g (P < .01). Correlated responses in body weight were .95 +/- .37 (140 d) and 1.13 +/- .42 kg (160 d) per generation for boars and .70 +/- .32 (130 d) and .64 +/- .46 kg (180 d) per generation for gilts. Response in backfat was .08 +/- .14 mm per generation in boars and .16 +/- .14 mm in gilts. Negative genetic trends occurred in age at puberty in both lines, but the difference between lines was not significant. At Generation 10, ovulation rate was .76 +/- .43 eggs more for gilts of the TS line than for C gilts. Genetic correlations of PWT with other traits are presented. Heritability of PWT was moderately high and its phenotypic variance was large; therefore, a high rate of response of 5.5% per generation occurred. Selection for PWT was not effective in decreasing age at puberty or increasing ovulation rate of daughters. PMID- 7982826 TI - Antiemetic drugs attenuate food aversions in sheep. AB - Ruminants learn to avoid many foods that contain toxins by associating the flavor of the foods with aversive postingestive feedback. We hypothesized the emetic system is a cause of aversive feedback, and three experiments were conducted to determine whether antiemetic drugs (diphenhydramine, metoclopramide, dexamethasone) would attenuate food aversions caused by the toxicant lithium chloride (LiCl). Lambs were assigned to one of four treatments: antiemetics plus LiCl (A + L), antiemetics alone (A), LiCl alone (L), or neither antiemetics nor LiCl (C). The LiCl was administered immediately after sheep ate oats, wheat, and milo in Exp. 1, 2, and 3, respectively. The antiemetics were given 1 h before and at the time LiCl was administered to sheep. Lambs that received antiemetics (A and A + L) consistently ate more grain than lambs that did not receive the drugs (C and L) (Exp. 1, P < .08; Exp. 2, P < .05; Exp. 3, P < .08), and there was no interaction between antiemetics and LiCl. Thus, the results of all three experiments were consistent with the hypothesis that antiemetic drugs attenuate food aversions caused by the toxicant LiCl because sheep receiving antiemetic drugs (Group A + L) ate more grain than sheep not receiving the drugs (Group L). In addition, we suggest aversive postingestive feedback limited intake of grain because sheep receiving antiemetic drugs (Group A) ate somewhat more grain than sheep not receiving the drugs (Group C). PMID- 7982827 TI - Influence of light dark cycles on estradiol-17 beta induced luteinizing hormone patterns of the prepuberal gilt. AB - Two groups of Yorkshire gilts (110 d of age) were maintained in two light regimens. Both light regimens consisted of 14 h of light and 10 h of darkness, but were 180 degrees out of phase. Gilts in Group 1 received light from 1200 to 0200 and gilts in Group 2 from 2400 to 1400. At approximately 140 d of age each group was divided into four subgroups of eight gilts each (1A, 1B, 1C, 1D or 2A, 2B, 2C, 2D). All gilts were blood sampled at 2-h intervals for 5 d commencing on d 142. The four subgroups received a single injection of estradiol (15 micrograms/kg body weight) on d 143 at either 2400 (A), 0600 (B), 1200 (C), or 1800 (D). For pigs in Groups 1A and 1D, the injection of estradiol coincided with the animals' "subjective day" and the injections given to Groups 1B and 1C with their "subjective night." When estradiol-17 beta (E2) was administered to the gilts during their subjective day the LH profile showed one peak, whereas when E2 was administered during dark hours the profile exhibited two peaks (P < .0001). In Group 2 for which the light cycle was reversed, the well-defined spikes of LH were found to coincide with the injections of estradiol administered during the dark hours. Smaller biphasic peaks of LH occurred when injections of estradiol coincided with the light hours.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7982828 TI - Transforming growth factor beta-1 facilitates establishing clonal populations of ovine muscle satellite cells. AB - Myogenic cells isolated from lamb fetuses (approximately mid-gestation) exhibited a concentration-dependent decrease in myogenic cell proliferation in response to transforming growth factor (TGF) beta-1 (P < .001). Half-maximal inhibition of proliferation occurred at approximately .05 ng of TGF beta-1/mL and maximal inhibition of proliferation occurred at approximately .1 ng of TGF beta-1/mL. The specificity of this inhibition was confirmed by neutralization of the activity following exposure to a TGF beta antibody. The TGF beta-1 also suppressed proliferation of ovine satellite cells isolated from 5-d-old lambs (P < .0035), but to a lesser extent than observed for embryonic cells. In contrast, TGF beta-1 did not significantly suppress serum-stimulated proliferation of ovine satellite cells isolated from 30- or 150-d-old lambs. Similarly, TGF beta-1 did not suppress proliferation of skeletal muscle fibroblast-like cells isolated from either fetal lambs or 150-d-old lambs. In fact, proliferation of fibroblast-like cells derived from embryonic ovine muscle was enhanced by exposure to TGF beta-1 at all levels tested; however, a concentration-dependent response was not observed. Media transfer experiments showed that conditioning of culture media by postnatally derived cells did not render TGF beta-1 inactive. The studies described in this manuscript suggest that sensitivity of ovine myogenic cells to the antiproliferative effect of TGF-beta may vary with the stage of development.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7982829 TI - Effect of dantrolene treatment on muscle metabolism and meat quality of anesthetized pigs of different halothane genotypes. AB - Muscle metabolism was studied in pigs of different halothane genotypes by taking blood and muscle biopsy samples during a 45-min preslaughter period of anesthesia. Dantrolene was administered to half the pigs of each genotype to investigate whether possible differences in muscle metabolism could be explained by differences in resting myoplasmic calcium concentrations. Dantrolene influenced muscle metabolism of all halothane genotypes to the same extent, leading to higher (P < .05) glycogen and creatine phosphate concentrations and lower (P < .05) lactate and creatine concentrations. Dantrolene could not reduce the small but significant (P < .05) differences observed in resting muscle metabolism between the genotypes, and halothane-positive pigs had lower (P < .05) glycogen and creatine phosphate contents. Postmortem muscle metabolism showed differences (P < .05) between the three halothane genotypes, with the highest rate of glycolysis in halothane-positive pigs. Dantrolene resulted in a significantly slower (P < .05) glycogen and creatine-P breakdown, which led to a less rapid (P < .05) accumulation of lactate and creatine in both muscles. Meat quality characteristics differed between the halothane genotypes but no PSE meat was detected. Dantrolene administration resulted in an elevation (P < .05) of the pH in the longissimus lumborum and in lower (P < .05) rigor values of the semimembranosus, both measured at 45 min after slaughter. Water-holding capacity was higher (P < .05) and Hunter L*-values lower (P < .05) is dantrolene-treated pigs than in the control animals.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7982830 TI - Calcium chloride concentration, injection time, and aging period effects on tenderness, sensory, and retail color attributes of loin steaks from mature cows. AB - Calcium chloride (CaCl2) injection effects on retail color changes and sensory traits of loin steaks from mature cows were studied. Left side strip loins (SL) of 10 carcasses were divided into three portions within .5 h postmortem. One was a control, and the other portions were injected with either 150 mM or 200 mM CaCl2. At 24 h postmortem, the chilled, right side SL was removed and the same treatments applied. Steaks from each treatment were evaluated for color changes during 5 d of retail display. Treatments were also divided into 7-d or 14-d aging periods. Warner-Bratzler shear (WBS) values and sensory evaluations of juiciness, tenderness, flavor intensity, flavor description, and overall palatability were obtained on all treatments. Concentration of CaCl2 had no effect on measures of color. However, injection at 24 h reduced colorimeter L values and visual color scores on d 1 and 2 of retail display and increased discoloration scores on d 3 (P < .05) compared with injection at .5 h. All steaks had greater than 40% discoloration when measured beyond d 3. Steaks aged 14 d exhibited significantly lower WBS values than steaks aged 7 d (P < .05). Injections of CaCl2 increased scores for juiciness, tenderness, and overall palatability, and aging improved tenderness, flavor intensity, flavor description, and overall palatability (P < .05). Cuts injected at 24 h had 8.3% and 8.8% higher yields than cuts injected at .5 h or controls, respectively (P < .05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7982832 TI - Recovery of amino acids at the distal ileum for determining apparent and true ileal amino acid digestibilities in growing pigs fed various heat-processed full fat soybean products. AB - Ten crossbred gilts fitted with simple T-cannulas at the distal ileum were used to determine the apparent and true ileal amino acid digestibilities in five different soybean products: extruded, jetsploded, micronized, or roasted full-fat soybeans (FFSB) and soybean meal (SBM). The gilts with an average initial body weight of 36 kg were fed the different diets according to a replicated 5 x 5 Latin square design. Gilts were fed twice daily at 0800 and 1830 at 2.6 times maintenance energy requirement. All diets were cornstarch-based and formulated to contain 16% CP from one of the five soybean products. The recovery of endogenous lysine at the distal ileum was determined using the homoarginine technique. This technique involved the guanidination of dietary lysine to homoarginine, to allow for a differentiation between undigested dietary lysine, represented by homoarginine, and endogenous lysine in the digestive tract of pigs consuming diets that contain guanidinated proteins. Chromic oxide and dysprosium chloride were included as indigestible markers in the normal and homoarginine diets, respectively. True digestibilities were only determined with the five gilts of one Latin square. Ileal digesta were collected for 24 h on d 8 and 10 of each 10 d experimental period. The apparent ileal protein digestibility was higher in SBM than in other soybean products (P < .05). In the heat-treated FFSB, the apparent protein digestibility varied between 69.0 and 81.6%. Recovery of endogenous lysine was affected by the diet (P < .01) and varied between 1,329 and 2,448 mg/kg of DM intake.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7982831 TI - Effect of lecithin on the apparent ileal and overall digestibility of crude fat and fatty acids in pigs. AB - Four barrows of approximately 40 kg initial body weight, fitted with post valvular T-cecum cannulas, were used to study the effect of lecithin as an external emulsifier on apparent ileal and overall digestibility of crude fat, fatty acids, and other dietary nutrients (DM, N, GE, crude fiber [CF], P, Ca, and Mg), as well as the utilization of N, GE, Ca, P, and Mg. Two levels of lecithin (0 and .24%) and two levels of rendered fat (0 and 6%) in cereal-soybean meal based diets were investigated according to a 4 x 4 Latin square design. No significant interactions were found between lecithin and rendered fat for apparent digestibility of crude fat as estimated at the end of the small intestine and the total digestive tract. Lecithin decreased the apparent ileal digestibility of C16:0 fatty acid (P < .1) and the apparent overall digestibility of C14:0 fatty acid (P < .05) and C18:2 fatty acid (P < .1). The apparent ileal and overall digestibility of crude fat (P < .001) and total fatty acids (P < .05) increased with the inclusion of rendered fat in diets. Furthermore, rendered fat increased the apparent ileal and overall digestibility of C14:0 (P < .01), C16:1 (ileal, P < .001; overall, P < .1), and C18:1 (P < .05) fatty acids and the apparent overall digestibility of C18:0 (P < .001) fatty acid. Lecithin had no impact on the apparent digestibility and retention (percentage of intake) of GE, N, total P, Ca, and Mg.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7982833 TI - The effect of protein intake on boar libido, semen characteristics, and plasma hormone concentrations. AB - To determine the effect of low protein intake on boar libido, semen characteristics, and plasma hormone concentrations, 20 crossbred boars (1 yr of age) were divided into 10 littermate pairs, and boars from within pairs were fed 44 g/kg of BW.75 per day of either a low-protein diet (7% CP) or a control diet (16% CP) with the same energy content (3.41 Mcal of ME/kg). During the first 16 wk and from wk 19 to 23, semen was collected two times per week. During wk 17 and 18, boars were subdivided within dietary treatment and semen was collected either two or seven times per week. Blood samples were collected at 12-min intervals for 6 h before and 1 h after an intravenous injection of GnRH (375 ng/kg of BW) during wk 24. All plasma samples were analyzed for LH and pooled samples were analyzed for estradiol-17 beta and testosterone. Boars with low protein intakes required more time to start ejaculation (P = .11, wk 0 through 7; P < .04, after wk 7), had a shorter duration of ejaculation (P < .09, wk 19 through 23), and had reduced semen volumes (P < .01, after wk 7) compared with boars on the control treatment. There was no interaction between dietary treatment and semen collection frequency (P > .39) for any of the semen or libido measurements. Testosterone and LH concentrations were not affected by protein intake (P > .5). However, concentration of estradiol-17 beta was greater in boars fed the control diet than in boars fed the low-protein diet (582 vs 202 pg/mL, respectively; P < .08). Estrogen concentrations in boars were negatively correlated with the time required for the boar to start ejaculating (r2 = .72). Boars with low protein intakes had reduced libido and semen volume. This reduction in libido and semen volume may be a result of a decrease in estradiol-17 beta concentration in circulation. PMID- 7982834 TI - The effect of energy and protein intakes on boar libido, semen characteristics, and plasma hormone concentrations. AB - To determine the effect of energy and protein intakes on boar libido, semen characteristics, and plasma hormone concentrations, 24 crossbred boars (1 yr of age) were allotted to one of three dietary treatments. Two protein levels (7.7 and 18.1 g/d of lysine) and two energy levels (6.1 and 7.7 Mcal/d of ME) were combined to create 1) low-energy and low-protein (ep), 2) low-energy and high protein (eP), and 3) high-energy and high-protein (EP) treatments. Semen was collected two times per week for 27 wk. During wk 28, blood samples were collected before and after a intravenous injection of GnRH (375 ng/kg of BW). The EP boars had higher (P < .01) ADG than the eP boars (373 vs 169 g), which had higher (P < .01) ADG than the ep boars (169 vs 92 g). Fewer EP and eP boars (zero of eight and two of eight, respectively) than ep boars (five of eight) consistently refused to mount the collection dummy (P < .05). During the final 20 wk of the semen-collection period, EP and eP boars had 33% longer durations of ejaculation (P < .04), had 60% greater semen and gelatinous fraction volumes (P < .03), but had 25% lower sperm concentration in their semen (P < or = .12) than ep boars. The EP boars produced 38% more sperm than the ep boars (P < .10). Baseline LH concentration, LH pulse frequency, LH pulse amplitude, testosterone concentration, and estradiol-17 beta concentrations were not affected by treatment (P > .10).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7982836 TI - Energy and protein metabolism of the Chinese pig. AB - Sixteen Chinese pigs (Meishan breed) from four litter outcome groups with initial weights ranging from 6 to 22 kg BW were used in a 28-d comparative slaughter experiment to determine the utilization of energy for maintenance and growth and the utilization of protein and amino acids (AA) by the Chinese pigs. Pigs were randomly allotted from litter outcome groups to four replicates of four pens each and to four treatments within replicates. A corn-soybean meal basal diet was formulated to provide all the nutrients except energy at twice the recommended levels for 10- to 20-kg pigs. The treatments were the basal diet fed at 3, 4, or 5% of BW. The fourth treatment was the initial slaughter group. As level of feeding increased, ADG increased linearly (P < .01) and gain:feed ratios increased quadratically (P < .06). Increasing the level of feeding had no effect on apparent digestibility coefficients of DM, N, or GE. Fecal N, urinary N, urinary urea N, and N retention increased linearly (P < .01) as feed intake increased. Level of feeding did not affect the DE, ME, or NE concentration in the diet. Metabolizable energy as a percentage of DE averaged 92.7% and was not affected by feeding level. Percentage of ether extract and DM of the empty body increased linearly (P < .01), but percentage of water decreased linearly (P < .01) with the level of feeding. Percentage of CP and ash of the empty body were not affected by the level of feeding (P > .05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7982835 TI - Availability of amino acids for 10- to 20-kilogram pigs: lysine and threonine in soybean meal. AB - The availabilities of lysine and threonine in soybean meal for 10- to 20-kg pigs were determined in two experiments using slope-ratio methodology. In the first experiment, a basal diet formulated to contain 6 g of lysine/kg, but adequate in all other amino acids, was supplemented with 1, 2, or 3 g of lysine/kg from either soybean meal or L-lysine-HCl. Each of the seven diets was available on an ad libitum basis to six individually penned pigs (barrows:gilts, 1:1) from an initial weight of 9.9 kg until they reached a live weight of 20.8 kg. Daily feed intake was similar among diets. Common-intercept multiple linear regression of daily live weight gain and gain:feed ratio on dietary lysine level indicate slope ratios (soybean meal:lysine.HCl) of .85 and .88, respectively. In Exp. 2, a basal diet formulated to contain 4 g of threonine/kg was supplemented with .65, 1.30, 1.95, or 2.60 g of threonine/kg from either soybean meal or L-threonine. Each of the nine diets was available on an ad libitum basis to six individually penned pigs (barrows:gilts, 1:1) from 9.9 to 21.0 kg live weight. As in Exp. 1, daily feed intake was similar among the nine diets. The slope ratios (soybean meal:L threonine) from common-intercept multiple regression analyses were .73 and .78 for daily weight gain and gain:feed ratio, respectively. Thus, the availabilities of lysine and threonine in soybean meal for young pigs were estimated to be 85 to 88% and 73 to 78%, respectively. PMID- 7982837 TI - The effect of spray-dried porcine plasma on growth performance in the early weaned pig. AB - A total of 904 weanling pigs were used to investigate the effects of 1) spray dried porcine plasma (SDPP), 2) blends of SDPP and spray-dried blood meal (SDBM), and 3) added dietary methionine in a SDPP-based diet on starter pig performance. In Exp. 1, 534 weanling pigs (initially 6.4 kg and 21 +/- 2 d of age) were used to determine the effects of either 0, 2, 4, 6, 8, or 10% SDPP and lactose as a replacement for dried skim milk in the Phase I diet (d 0 to 14 postweaning). All pigs were fed the same diet from d 14 to 28 postweaning. Average daily gain from d 0 to 14 increased (linear, P < .01) with increasing SDPP. From d 14 to 28, ADG decreased (linear, P < .03) as level of SDPP fed during Phase I increased. However, for d 0 to 28, ADG was increased (linear, P < .01) with increasing SDPP in the Phase I diet. Feed intake increased with increasing SDPP from d 0 to 14 and d 0 to 28 (quadratic, P < .04 and P < .08, respectively); however, gain/feed (G/F) was not affected. In Exp 2, 298 weanling pigs (initially 5.5 kg and 19 +/- 2 d of age) were used to determine the effects of replacing SDPP with SDBM in the Phase I diet. Pigs were fed either a diet containing 10% SDPP or diets with SDBM replacing 25, 50, 75, or 100% of the lysine provided by the SDPP.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7982838 TI - Utilization of colostral energy by the newborn pig. AB - Twenty-five newborn pigs were used to evaluate the energy utilization of sow colostrum by pigs maintained for 24 h in respiratory chambers at an environmental temperature of 33 degrees C. Within a litter, five neonatal pigs were obtained before nursing and allotted on the basis of initial body weight (IBW) at 3 h of age to one of the five treatments: killed, fed intragastrically 6, 12, or 18 g of sow colostrum/kg IBW per meal, or fasted. A total of 24 meals at 60-min intervals was provided and pigs were killed 1 h after the last meal. Heat production (HP) was measured by indirect calorimetry and energy retention (ER) was calculated by metabolizable energy (ME)-HP. A balance technique was used to determine nitrogen (N) retention, and comparative slaughter technique (CST) was used to determine fat accretion and glycogen mobilization. The ME intake increased quadratically (P < .01) with the level of colostrum intake. The efficiency of ME for ER was 91 +/- 4%. Nitrogen absorbed was utilized with an efficiency of 89 +/- 3% for N retention, and the estimated energy cost of 1 kcal of protein synthesized was 1.11 +/- .11 kcal. Thermoneutral maintenance ME requirement was low (68.5 kcal.kg avg BW-1 x 24 h-1) because of the low activity of pigs. Fasting heat production (FHP) measured by calorimetry and CST amounted to 56.4 and 60.4 kcal.kg avg BW-1 x 24 h-1, respectively. Estimates of the contribution of glycogen and protein catabolism to FHP were 83.0 and 6.8%, respectively.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7982839 TI - Local and systemic immune responses to soybean protein ingestion in early-weaned pigs. AB - The development of local and systemic immune responses to soybean proteins was investigated in early-weaned pigs. Pigs were given either antigenic (ASP, n = 10 pigs) or non-antigenic (NASP, n = 8 pigs) soybean products (6 g of protein/d) from d 5 to 9 of age by stomach tube. After weaning at d 21, pigs were fed diets containing the corresponding soybean products and slaughtered between d 28 to 30. Diarrhea was 2.4-fold more frequent, the size of duodenal villi was reduced by 24 to 36%, and the eosinophil density in the duodenal mucosa was 13 times greater (P < .02) in the ASP pigs compared with the NASP pigs. A larger erythema area (P = .006) was observed in the ASP group than in the NASP group 30 min after an intradermal injection of glycinin, but no significant difference could be detected with alpha- or beta-conglycinin or whole soybean extracts. No difference in skin fold thickness was apparent between groups 24 h later. Intestinal, mesenteric lymph node, and blood lymphocytes did not proliferate when cultured with soybean proteins, regardless of dietary treatment. By ELISA, no difference between groups was observed in the circulating levels of total immunoglobulins (Ig) and IgM. Immunoblotting patterns of raw soybean with sera from 28-d-old pigs showed two bands (22 and 36 kDa) recognized by IgA and IgM, respectively, in the ASP group only. Finally, the adverse effects observed with antigenic soybean flour can be overcome by the use of alcohol-treated products.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7982840 TI - Morphological and functional characteristics of preovulatory follicles in large white and Meishan gilts. AB - Research was conducted to determine whether there are preovulatory follicular characteristics unique to Chinese Meishan (MS) sows that may contribute to their high prolificacy compared to that of European breeds. Follicles were recovered during the late follicular phase, following altrenogest withdrawal, from the ovaries of MS and Large White (LW) gilts before and after the administration of hCG given to mimic the LH surge. Following incubation of whole follicles for 1 h in vitro, media were collected for measurement of estradiol-17 beta, testosterone, and progesterone concentrations, and follicles were either fixed to assess number of granulosa and theca interna cells or cut into explants to test for aromatase activity over an additional 24-h incubation period. In MS gilts, follicles were smaller before and after hCG, although their growth was greater after hCG than was the growth of LW follicles. The LW and MS follicles contained relatively similar numbers of theca interna cells, whereas the numbers of granulosa cells in MS follicles were marginally (before hCG) or significantly (after hCG) less than those found in LW follicles. Before hCG, follicles of comparable size from both breeds produced similar amounts of estradiol and progesterone, whereas MS follicles produced less (P < .05) testosterone. Aromatase activity was not stimulated by FSH in either case, although a breed x follicle size interaction (P < .05) indicated a different pattern of aromatase activity between the breeds. After hCG, testosterone production was similar in MS and LW follicles, but estradiol (P < .05) and progesterone (P < .01) production were greater in MS follicles.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7982841 TI - Kinetics of splanchnic progesterone metabolism in ewes fed two levels of nutrition. AB - The objective of this study was to determine whether chronic nutritional treatment influences progesterone (P4) metabolism by splanchnic tissues and to develop a mathematical model of P4 metabolism in ewes. Five ovariectomized (ovx), multiparous ewes were assigned to a high feed intake and five multiparous ovx ewes were assigned to a low feed intake. The ewes with high feed intake received daily ME intakes of 99 kcal/BWkg.75, and the ewes with low intake received daily ME intakes of 63 kcal/BWkg.75. Catheters were placed surgically in the abdominal aorta, the portal vein, a branch of the hepatic vein, and a mesenteric vein. Blood and plasma flows across visceral organs were determined by marker dilution (p-aminohippuric acid), and P4 was determined with a RIA. The net splanchnic P4 flux and oxygen (O2) consumption were determined during five rates of P4 infusion into the jugular vein (112, 224, 449, 897, and 1,795 micrograms/h). Splanchnic O2 consumption was greater (P = .05) in the ewes with high feed intake. Net splanchnic P4 flux did not differ (P > .10) between nutritional treatments. The correlation between net splanchnic P4 flux and O2 consumption did not differ from zero (P = .69). Net splanchnic P4 flux was related linearly to plasma arterial P4 concentration. Splanchnic tissue clearance rate was 18% of the infusion rate. The behavior of the P4 model indicates that whole-body P4 metabolism is the sum of first-order kinetic reactions. The data indicate that splanchnic clearance of P4 is not affected by nutritional status. PMID- 7982842 TI - Supplemental protein for beef cattle grazing dormant intermediate wheatgrass pasture: effects on nutrient quality, forage intake, digesta kinetics, grazing behavior, ruminal fermentation, and digestion. AB - Sixteen ruminally cannulated yearling beef cattle (British x British; average BW = 295 +/- 25 kg; three steers and one heifer per treatment) grazing dormant intermediate wheatgrass (Thinopyrum intermedium Host) were allotted to four treatments: 1) no supplement (CON); 2) alfalfa hay (ALF; .52% of BW); 3) cottonseed meal (CSM; .22% of BW); and 4) corn gluten meal-wheat bran feed (CGMWBF; .36% of BW). Supplements were formulated (DM basis) so that intakes were isonitrogenous and were provided once daily (0700). Sampling periods were in February (FEB; .96% N in masticate), March (MAR; 1.06% N in masticate), and April (APR; 1.12% N in masticate) following an initial 21-d adaptation period. Daily grazing time was 1.1 to 1.5 h longer (P < .05) for CON cattle than for supplemented cattle. Forage OM intake (OMI) was not altered (P > .15) by supplemental protein; however, total OMI was greater (P < .04) for supplemented than for unsupplemented cattle. Harvesting efficiency (grams of OM intake kilogram of BW-1.minute spent grazing-1) was greater (P < .05) for cattle fed CSM than for those fed CGF or CON; cattle fed ALF were intermediate in harvesting efficiency. Ruminal fluid kinetics, in situ rate and extent of NDF digestion, and total VFA concentration were not influenced (P > .10) by type of supplemental protein. Ruminal NH3 N concentration exhibited a treatment x sampling time interaction (P < .05). Type of protein supplement did not seem to affect most digestion measures; however, harvesting efficiency was influenced by supplement type. PMID- 7982843 TI - Metabolism of tritiated D-alpha-tocopherol and D-alpha-tocopheryl succinate in intraruminally dosed sheep. AB - The comparative disposition (absorption, plasma disposition, tissue distribution) of D-alpha-tocopherol and of D-alpha-tocopheryl succinate (forms of vitamin E) was investigated in 10 ruminally cannulated wethers. Tritiated tocopherols (4 microCi/kg BW) were administered directly into the rumen. Plasma and ruminal fluid activity were regularly measured from the time of administration to 96 h after administration. Radioactivity in lymph was measured in four additional wethers dosed intraruminally (100 microCi) with the same tritiated compounds. Lymph was collected from the cannulated thoracic duct during the first 24 h after the administration. Wethers were killed and selected tissues were measured for their tocopherol activity. Plasma and ruminal fluid specific activity vs time were modeled using appropriate compartmental and noncompartmental approaches. It was shown that there was a large difference in the relative bioavailability of the two compounds with a four times higher (P < .05) relative availability of D alpha-tocopherol than of D-alpha-tocopheryl succinate. This was explained in terms of incomplete hydrolysis of tocopheryl succinate before absorption. By direct ruminal fluid measurement, it was estimated that tocopherol behaves similarly to a soluble ruminal marker with a ruminal transit time of approximately 19 h. In plasma, the total mean residence time was 148 h for D alpha-tocopherol and 106 h for D-alpha-tocopheryl succinate. The lymph activity was mainly associated with tocopherol both after tocopherol and tocopheryl succinate administration. Tissue concentration of radioactivity was higher (P < .05) for sheep dosed with tocopherol than for those dosed with the tocopheryl succinate, confirming the difference in bioavailability of the two compounds. PMID- 7982844 TI - Energy cost of standing and circadian changes in energy expenditure in the preruminant calf. AB - An experiment was conducted with four preruminant calves to measure the energy cost and the diurnal pattern of physical activity in tethered, fed calves and to determine whether differences in activity could interfere with the interpretation of circadian changes in heat production. Measurements were carried out in large respiration chambers (3,650 L of inner volume), and a computation method was presented that allowed the calculation of the energy cost of standing for each standing period. This cost averaged 449 cal.kg BW-1.h-1 (SE = 41.6, n = 4). It represented a 23 to 27% increase in heat production above that measured in the lying state. This estimate and its standard error were lower than values obtained by regression (2,131 cal.kg BW-1.h-1, SE = 862.2, n = 8). The energy cost of standing was highest after meal times and lowest at night. These variations could reflect the nonuniform activity patterns of calves while standing. The time spent standing per hour showed the same variations during the day as the energy cost of standing. Noteworthy, the elevated energy expenditure measured in the 1st h after the morning meal was due to activity cost rather than to meal thermogenesis. Standardization of diurnal heat production profiles to a given activity pattern thus seemed to be necessary. PMID- 7982845 TI - Influence of a propionate load in fed or unfed lambs on blood metabolites and hormone patterns. AB - Six crossbred wether lambs were used in a crossover design to determine the effects of a 3-d feed and water deprivation period on metabolite and hormonal response to a propionate load. During each period of the crossover design all lambs were limit-fed (700 g/d) a 36% concentrate diet for 16 d, then three of the six lambs were deprived of feed and water for 3 d. All lambs were then limit-fed (700 g/d) the 36% concentrate diet (realimentation). Propionate loading tests were performed 4 h before feeding on d 1, 5, and 9 of the realimentation period. A 1.84 M propionate solution (3 mmol/kg BW) was infused into the right jugular vein and blood samples were obtained from the left jugular vein at intervals for 4 h after infusion. At the end of the 3-d feed and water deprivation period, fed lambs had greater serum insulin (P < .02), acetate (P < .01), and glucose (P < .05) concentrations and lower plasma-free fatty acids (P < .01) and urea N (P < .05) concentrations than unfed lambs. On d 1 of realimentation, previously unfed lambs had greater postinfusion growth hormone (P < .05), free fatty acid (P < .01), propionate (P < .07), lactate (P < .04), and urea N (P < .05) concentrations and lower serum insulin (P < .02), and acetate (P < .03) concentrations than fed lambs. Serum prolactin concentrations increased (P < .02) postinfusion in unfed lambs but not in fed lambs.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7982846 TI - Influence of yeast culture supplementation and advancing season on steers grazing mixed-grass prairie in the northern Great Plains: I. Dietary composition, intake, and in situ nutrient disappearance. AB - Twelve beef steers (368 +/- 25.3 kg) and four beef heifers (559 +/- 79.5 kg) fitted with ruminal cannulas were used to evaluate effects of yeast culture (YC) and advancing season on dietary chemical composition, intake, and in situ CP and NDF degradation. Treatments were control and YC supplementation (28.4 g.steer-1.d 1 dosed ruminally). Steers grazed from late June to early November 1991 on mixed grass prairie. Experimental periods consisted of 10 d for adaptation and a 13-d collection phase. Forage samples collected from YC-supplemented steers had greater (P < .10) soluble N and in vitro OM disappearance than forage from controls throughout the grazing season. Organic matter intake was greater (P < .10) by YC-supplemented steers during June. Fecal output and OM intake increased (P < .10) from June to September. Increases (P < .10) in in situ NDF disappearance were noted at 8, 16, and 24 h in June, at 8, 48, and 72 h in July, and at 8 h in August for the YC treatment group. Supplemental YC did not affect (P > .10) rate or lag time of NDF disappearance. In situ CP disappearance (ISCPD) was greater (P < .10) at all times except 48 h in June, at 48 and 72 h in July, and at 0, 4, 8, and 12 h in August for YC-supplemented steers. Steers supplemented with YC had an increased extent (P < .10) of ISCPD in July and an increase in CP degradation rate in June; however, total CP degradation was greater (P < .10) during June for control than for YC steers.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7982847 TI - Influence of yeast culture supplementation and advancing season on steers grazing mixed-grass prairie in the northern Great Plains: II. Ruminal fermentation, site of digestion, and microbial efficiency. AB - Twelve ruminally and duodenally cannulated beef steers (initial BW 368 +/- 25.3 kg) and four ruminally cannulated beef heifers (initial BW 559 +/- 79.5 kg) were used to evaluate the effects of yeast culture (YC) and advancing season on ruminal fermentation, microbial protein synthesis, ruminal fluid kinetics, and site of digestion. Treatments were control and YC supplementation (28.4 g.steer 1.d-1 dosed ruminally). Steers grazed from late June to early November 1991 on mixed-grass prairie. Ruminal pH decreased (P < .10) from late July to early October. Fluid dilution rate decreased (P < .10) as the grazing season advanced, whereas ruminal fluid volume and flow rate increased (P < .10) from late July to early October. Ruminal ammonia concentration (milligrams/deciliter) was lower (P < .10) during late July and late August than during late June and early October at 4, 8, 12, and 16 h after sunrise in YC-supplemented steers. Molar proportions of propionate and butyrate were greater (P < .10) in control than in YC supplemented steers at 0, 4, 12, and 24 h and 0, 4, and 12 h after sunrise, respectively, during late July. Acetate (mol/100 mol) was greater (P < .10) during late July and late August than in late June and early October for YC supplemented steers at 0, 4, and 8 h after sunrise. True ruminal OM digestion was greatest (P < .10) in late June, intermediate in late July and late August, and least in early October. Supplementation with YC increased (P < .04) true ruminal OM digestion in late June and late July. Steers receiving YC had greater (P < .07) duodenal bacterial N flow in late July. These data indicate that yeast culture supplementation can increase true OM digestibility early in the grazing season. Advancing season seems to result in increased ruminal fluid volume, lower true ruminal OM digestion, and greater microbial efficiency. PMID- 7982848 TI - Why the study of animal behavior is associated with the animal welfare issue. AB - Of the various disciplines within the animal sciences, the issue of animal welfare has been most closely associated with ethology, the study of animal behavior. Prior to the modern welfare movement, applied ethology was primarily involved in studies on feeding and reproductive behavior. The emphasis on freedom of movement and mental experiences in animal welfare resulted in the field of applied ethology developing its current welfare interests. During the past 30 yr, applied ethology has been used to gather appropriate information to develop alternate management systems that accommodate normal behavior. The issue of behavioral needs has been addressed and research interest in motivation has developed. Preference tests have been used for their traditional role of improving comfort and have been modified to assess motivation as well. We have used abnormal behaviors as indicators of poor welfare and are shifting our emphasis to causative factors of these behaviors. The emotional states and cognitive abilities of animals have been studied but will become an increasingly important component of behavior research into animal welfare in the future. PMID- 7982849 TI - Breeding for profit: synergism between genetic improvement and livestock production (a review). AB - Fifty years of research in animal breeding and genetics are examined from four perspectives: 1) genetic prediction, 2) animal testing and selection schemes, 3) dissemination of genetic improvement, and 4) definition of breeding objectives in economic form. Breeding in all classes of livestock has moved from a purebred appearance orientation to a performance (either purebred or crossbred) orientation. Unfortunately, the evolution from a performance orientation to an economic orientation is incomplete, especially for some livestock classes. Placing breeding objectives into a mathematical form on a sound economic basis is key to integrating modern developments in animal breeding into more purposeful industry programs. Procedures used to develop such objectives are reviewed with attention to common approaches. Where consensus is reached about a breeding objective (in economic form) for a class of livestock, this objective can be used in conjunction with genetic predictions to rank animals within a breeding population. Ranking without undue attention to herd of origin facilitates a pyramid-shaped hierarchy of animals that can be fundamental to the functioning of breeding enterprises contributing improvements to operations concerned with production. Genetic improvements should flow from proven genetically superior animals to improved production systems. The tiers of the pyramid need to be organized relative to animals with differing levels of economic evaluation. PMID- 7982850 TI - Rapid communication: an SstI restriction fragment length polymorphism at the swine OCT11 locus. PMID- 7982851 TI - Rapid communication: an XbaI restriction fragment length polymorphism at the Porcine T-complex 1 (TCP1) locus. PMID- 7982852 TI - Rapid communication: polymerase chain reaction-restriction fragment length polymorphism in the bovine growth hormone gene. PMID- 7982853 TI - Anaplastic large-cell lymphoma presenting primarily in bone in a patient with AIDS. AB - Non-Hodgkin's lymphomas have been recognized as an important and frequently fatal part of the spectrum of diseases associated with HIV infection. These are most often high-grade B-cell lymphomas usually of immunoblastic and small cell non cleaved subtypes. Sporadic reports of T-cell lymphomas associated with HIV infection are found in the literature. Two have been reported to be CD30 positive presenting with lymph node and skin involvement. We report a case of an AIDS patient with a T-cell anaplastic large-cell lymphoma that was CD30-positive and presented in bone. This is most probably a sporadic event rather than another part of the AIDS-associated spectrum of disease. PMID- 7982854 TI - Comparison of image (CAS 200) and flow cytometry determined DNA content of paraffin-embedded Hodgkin's disease tissue. AB - To assess the reliability of DNA estimation using image cytometry, deparaffinized lymph nodes from 70 patients with Hodgkin's disease were examined and the results obtained were compared with those from flow cytometry. Image analysis without discriminating between the various cell types, as found in Hodgkin's disease, revealed no separate aneuploid peak. Selecting on morphologically defined nuclear types DNA aneuploidy was detected in 20% of the cases (14/70). The aneuploid populations were limited to the population of nuclei defined as Reed-Sternberg (RS)-like or medium-sized lymphocytes. Benign lymph nodes DNA aneuploidy was not found in any of the controls. Comparison of DNA histograms obtained by image and flow cytometry showed aneuploid peaks using image cytometry in 4 of 30 diploid and 10 of 40 aneuploid flow histograms. In conclusion, image analysis using the CAS 200 system as compared to flow cytometry is more time-consuming and less sensitive to assess ploidy status, although it may provide extra information in some selected cases. Evidence is obtained that DNA aneuploidy in Hodgkin's disease is preferentially expressed by cells with the RS/H-like and medium-sized lymphocyte morphology. PMID- 7982855 TI - Effect of dibutyryl cyclic AMP and interferon-gamma on Fc gamma receptor expression on eosinophils. AB - We studied the effect of dibutyryl cyclic adenosine-3',5'-monophosphate (dbcAMP) and several cytokines on the expression of IgG Fc receptor subclasses (Fc gamma RI, Fc gamma RII, and Fc gamma RIII) and low-affinity IgE Fc receptors (Fc epsilon RII/CD23) on peripheral eosinophils and on eosinophils differentiated in vitro from cord blood mononuclear cells by interleukin 5 (IL-5). These eosinophils expressed Fc gamma RII, and few, if any, Fc gamma RI and Fc gamma RIII as determined by flow cytometry with specific monoclonal antibodies. dbcAMP enhanced the Fc gamma RII expression, but did not induce the Fc gamma RI and Fc gamma RIII expression. Interferon-gamma (IFN-gamma) enhanced Fc gamma RII expression at the same degree as did dbcAMP. IFN-gamma also induced Fc gamma RIII expression on peripheral eosinophils but not on eosinophils grown in the presence of IL-5. Eosinophils grown in the presence of IL-5 showed a relatively immature phenotype, determined by electron microscopy and the low content of eosinophil cationic protein. Contrary to its enhancing effect on Fc gamma RII expression, dbcAMP suppressed the IFN-gamma-induced Fc gamma RIII expression on peripheral eosinophils. Other cytokines examined did not show any effects on Fc gamma R expression. Fc epsilon RII/CD23 expression was neither detected nor induced. These results indicate that expression of Fc gamma RII and Fc gamma RIII on eosinophils is regulated differently and that cAMP and IFN-gamma play important roles in the regulation of Fc gamma R expression. PMID- 7982856 TI - Conduct disorder: long-term outcomes and intervention effectiveness. AB - OBJECTIVE: To review the literature on conduct disorder in two areas: long-term outcome and the effects of interventions. METHOD: The sources of the articles for review were computer searches, but the articles were selected for this review to illustrate key findings in the long-term outcome area and to review critically four intervention strategies to prevent or treat conduct disorder, namely, parent and family-targeted programs, social-cognitive programs, peer and school-based programs, and community programs. RESULTS: Conduct problems in childhood predict the same increased rates of psychiatric disorder overall in men and women but the patterns are different: for externalizing disorders, the prediction is stronger in men and for internalizing disorders, the prediction is stronger in women. In the intervention domain, the literature provides limited evidence of the effectiveness of either primary or secondary prevention. CONCLUSIONS: Prospective studies of community samples of children provide the best opportunity to understand more thoroughly the adult outcomes of conduct disorder. Because of the heavy burden of suffering of conduct disorder, and the limited effectiveness of clinical interventions, there is a compelling argument in favor of an increased emphasis on primary prevention efforts. PMID- 7982857 TI - Listening to psychotherapy. PMID- 7982858 TI - Personality disorder, personality traits, impulsive violence, and completed suicide in adolescents. AB - OBJECTIVE: This study was designed to assess the association between personality disorders, personality traits, impulsive violence, and suicide. METHOD: Personality disorders and traits in 43 adolescent suicide victims and 43 community controls were assessed from the parents, using semistructured interviews and self-report forms. RESULTS: Probable or definite personality disorders were more common in suicide victims than in controls, particularly Cluster B (impulsive-dramatic) and C type (avoidant-dependent) disorders. Suicide victims also showed greater scores on lifetime aggression, even after controlling for differences in psychopathology between suicides and controls. CONCLUSIONS: Personality disorders and the tendency to engage in impulsive violence are critical risk factors for completed suicide. PMID- 7982859 TI - Suicidal children grow up: suicidal behavior and psychiatric disorders among relatives. AB - OBJECTIVE: This paper reports comprehensive data on psychiatric symptoms and disorders and medical problems of first- and second-degree biological relatives of prepubertal children who have contemplated or attempted suicide. METHOD: Standard family study and family history interview techniques were used to obtain information about psychopathology and medical illness in 488 first- and 1,062 second-degree relatives of 25 child psychiatric inpatients who reported suicide attempts, 28 child psychiatric inpatients who contemplated suicide, 16 nonsuicidal child inpatients, and 54 normal children. RESULTS: Suicidal behavior in children was associated with suicidal behavior in their families, although no first-degree relatives committed suicide. More first-degree relatives of child suicide attempters, compared to first-degree relatives of normal children, had antisocial personality disorder, assaultive behavior, and substance abuse. Mood disorders in first-degree relatives were not associated with child suicidal behavior. No significant associations were identified for psychopathology of second-degree relatives and child suicidal behavior. CONCLUSIONS: The results suggest the importance of evaluating familial psychopathology during assessments of suicidal children. Self-directed and externally directed violence, antisocial personality disorder, and substance abuse of relatives of suicidal children should be studied to elucidate the etiology of youth suicidal behavior. PMID- 7982860 TI - Role of the mother's touch in failure to thrive: a preliminary investigation. AB - OBJECTIVE: This study investigated the hypothesis that specific types of maternal touch that might promote infant growth are reduced in cases of failure to thrive (FTT) and tested reports that maternal physical interaction and physical affection are diminished in FTT. METHODS: Frequencies of operationally defined maternal touch categories were scored by blinded raters from videotaped mother child feeding and play interactions of 21 children, aged 9 to 19 months, with FTT and 18 normally growing comparison children. After scoring and statistical analyses were completed, investigators unblinded to group status and clinical data reviewed the videotapes of the dyads with the lowest touch scores. RESULTS: Mothers of children with FTT provided less matter-of-fact touch in feeding (p = .017) and unintentional touch in play (p = .048) than the comparison group, and there was a trend (p = .082) for them to provide less proprioceptive stimulation in play. Unblinded case reviews indicate that, among children with FTT, extremely infrequent touch signals a marked touch aversion by either the mother or child. CONCLUSIONS: Types of maternal touch that may promote growth or facilitate feeding are reduced in FTT, due, in extreme cases, to maternal or child touch aversion. Clinicians evaluating FTT should be alert to very infrequent touch in the mother-child interaction and consider whether it may represent a maternal intolerance of physical contact with her infant or a problem with the infant's feeding competence. PMID- 7982861 TI - Attachment in mothers with anxiety disorders and their children. AB - OBJECTIVE: This study examined adult attachment in mothers diagnosed with anxiety disorders and child-mother attachment in their children. METHOD: Eighteen mothers with Axis I anxiety disorders completed the Adult Attachment Interview and standardized questionnaires. These mothers and their preschool children (n = 20) then participated in the Strange Situation Procedure. RESULTS: All mothers were classified as nonautonomous with respect to attachment, with 78% judged unresolved. When those judged unresolved were reassigned to their alternate categories, the proportion of nonautonomous mothers was 61%. Eighty percent of the children were classified as insecurely attached, with 65% judged disorganized. When those judged disorganized were reassigned to their alternate categories, the proportion of insecurely attached children was 55%. Sixty-five percent of the children matched their mother's attachment classification. Mothers of securely attached children reported fewer recent life events, fewer depressive symptoms, and a greater sense of parenting competence than mothers of insecurely attached children. CONCLUSIONS: These results suggest that attachment measures can be applied to anxious populations. The high rate of insecurity among offspring of anxious mothers indicates a need for longitudinal studies of these children. PMID- 7982862 TI - Sleep problems in toddlers: effects of treatment on their daytime behavior. AB - OBJECTIVE: This study investigated the effects of a treatment program for severely sleep-disturbed children on their daytime interaction with their mothers. METHOD: Twenty-eight children with serious sleep problems and 30 matched controls, aged 12 to 36 months, were compared on behavior rating scales, on sleep patterns, and during play and feeding interactions with their mothers before and after an intervention program. RESULTS: After treatment the sleep-disturbed children improved in their behavior, in their sleep patterns, and during feeding interactions with their mothers. However, the behavior of the children but not that of their mothers improved. CONCLUSIONS: The findings of this study indicate that a brief behavioral intervention program focused on helping families manage children with sleep disturbances can generalize to daytime mother-child interactions. This suggests that a compromised relationship in early life may be modified by rather simple interventions since changes of one behavioral system may modify the total relationship of young children with those caring for them. PMID- 7982863 TI - Parental separation, adolescent psychopathology, and problem behaviors. AB - OBJECTIVE: This paper examines the effects of parental separation on the occurrence of adolescent psychopathology and problem behaviors at age 15 years. METHODS: Data collected during the course of a 15-year longitudinal study were used to examine a sample of 935 children with respect to exposure to parental separation during childhood, measures of adolescent psychopathology and problem behaviors at age 15 years, and prospectively collected confounding factors. RESULTS: Children exposed to parental separation during childhood had elevated risks of a range of adolescent problems, including substance abuse or dependence, conduct or oppositional disorders, mood and anxiety disorders, and early-onset sexual activity. However, adjustment for confounding factors explained a large amount of the increased risks of adolescent disorder, and after adjustment for confounders the odds ratios between exposure to parental separation and adolescent outcomes ranged from 1.07 to 3.32 with a median value of 1.46. The ways in which boys and girls responded to parental separation were similar. CONCLUSIONS: While the results suggested that children exposed to parental separation had increased risks of adolescent problems, much of this association appeared to be spurious and arose from confounding social and contextual factors that were present in the child's family before parental separation. However, even after such control, the results suggested that exposure to parental separation during childhood was associated with small but detectable increases in risks of adolescent conduct disorder, mood disorder, and substance abuse disorders. PMID- 7982864 TI - The efficacy of psychoanalysis for children: prediction of outcome in a developmental context. AB - OBJECTIVE: This is the third report from a chart review of 763 cases of child psychoanalysis and psychotherapy at the Anna Freud Centre. This paper examines the way in which the age of a child or adolescent at the time of treatment in psychoanalytic psychotherapy relates to the outcome of that treatment. METHOD: One hundred twenty-seven children were selected from each of three age bands (younger than 6 years, 6 to 12 years, and adolescents); they were matched on broad diagnostic grouping, gender, socioeconomic status, global adaptation (Children's Global Assessment Scale), and frequency of sessions. Outcome was indicated by diagnostic change and clinically significant change in adaptation. RESULTS: Younger children were more likely to show significant improvement. Children younger than 12 benefited from intensive (four or five times weekly) treatment more than from nonintensive (one or two times weekly) treatment; this was not true of adolescents. There were interactions between certain diagnostic categories, age, and outcome. Predictors of good and poor outcome were different for the three age groups, further highlighting the importance of a developmental perspective. CONCLUSIONS: Within the limitations of a retrospective design, this study suggests that in psychodynamic treatment, younger age is an advantage and developmental factors considerably affect the outcome of this form of therapy. PMID- 7982865 TI - Structure of DSM-III-R criteria for disruptive childhood behaviors: confirmatory factor models. AB - OBJECTIVE: The aims of this analysis were to examine the extent to which DSM-III R criteria for disruptive behavior patterns were consistent with the system of diagnoses proposed. Particular attention was paid to (1) whether oppositional defiant disorder is factorially distinct from conduct disorder (CD) and (2) the extent to which CD can be further classified into overt and covert CD behaviors. METHOD: Data were gathered on DSM-III-R criteria for disruptive behavior patterns for a sample of 739 New Zealand 15-year-olds using data provided by parental and self-report. These data were supplemented by officially recorded police contact data. RESULTS: Application of methods of confirmatory factor analysis suggested that the diagnostic criteria in DSM-III-R reflected a constellation of distinct but highly correlated behavioral domains, with these domains corresponding to oppositional defiant disorder, overt CD (aggression, violence), covert CD (theft, dishonesty), and attention-deficit hyperactivity disorder behavior. Results of second-order factor analysis methods suggested that these dimensions reflected two general higher-order factors, with the first factor reflecting the extent to which the individual displayed behavioral symptoms of oppositional defiant disorder and attention-deficit hyperactivity disorder and the second reflecting the extent to which the individual expressed antisocial, conduct-disordered behaviors. CONCLUSIONS: The results of confirmatory factor analysis generally support and validate the diagnostic classifications proposed in DSM-III-R but suggest possible refinements that draw distinctions between overt and covert expressions of CD. PMID- 7982866 TI - The Children's Global Assessment Scale in clinical practice: an empirical evaluation. AB - OBJECTIVE: The purpose of this study was to examine characteristics of the Children's Global Assessment Scale (CGAS) in the context of clinical practice. METHOD: Ninety-five children admitted to a psychiatric inpatient unit were rated by their attending psychiatrist and by milieu staff on the CGAS. Measures of severity and type of symptomatology; social, behavioral, and school competence; intellectual level; social relatedness; and family stress were completed by parents and staff raters. RESULTS: Results indicated that there was significant convergence in CGAS ratings by independent raters. CGAS ratings were unrelated to measures of symptomatology but were significantly related to indices of children's competence. CONCLUSIONS: This pattern of results diverged from findings from highly controlled research settings and indicated that CGAS ratings obtained in clinical contexts may reflect evaluations of functional competence rather than severity of symptomatology. PMID- 7982867 TI - Urinary catecholamines in attention-deficit hyperactivity disorder with and without comorbid anxiety. AB - OBJECTIVE: To determine whether there are differences in noradrenergic or adrenergic functioning in children with attention-deficit hyperactivity disorder (ADHD) with and without anxiety. METHOD: ADHD children with and without a comorbid overanxious (ANX) disorder were compared to each other and to normal controls in terms of 2-hour urinary excretion of norepinephrine (NE), epinephrine (EPI), and their metabolites. All subjects performed a fixed series of mentally stressful tasks during the collection period. RESULTS: Children with ADHD, regardless of comorbid anxiety, excreted more normetanephrine (NMN), the chief extracellular metabolite of NE, than controls, as well as more vanillylmandelic acid. Children with ADHD alone had lower NE/NMN and EPI/metanephrine ratios compared to controls. Children with ADHD/ANX excreted more EPI than ADHD children without anxiety. CONCLUSIONS: Children with ADHD may have a higher tonic activity of the noradrenergic system than controls, while children with comorbid ADHD/ANX may be differentiated from those with ADHD alone by higher adrenergic activity. PMID- 7982868 TI - Salivary testosterone and cortisol in disruptive children: relationship to aggressive, hyperactive, and internalizing behaviors. AB - OBJECTIVE: To test predictions that basal salivary testosterone and cortisol are related to antisocial and internalizing behaviors, respectively, and that cortisol moderates the testosterone-aggression relationship. METHOD: Saliva samples were assayed to determine testosterone and cortisol levels in 40 clinic referred disruptive children (aged 7 through 14 years) who were rated on aggression, inattention/overactivity, and internalizing behavior by parents, teachers, and clinic staff members. RESULTS: Results indicated significant positive relationships between testosterone and staff-rated aggression and between cortisol and parent-rated internalizing behavior. A significant negative relationship was found between cortisol and staff-rated inattention/overactivity. No interactions between testosterone and cortisol were found. These results were maintained regardless of age, racial background, height, weight, diagnosis, or medication status. CONCLUSIONS: Results suggest moderate relationships between testosterone and observed aggression, and between cortisol and emotional behaviors, in a group of disruptive children. Cortisol did not moderate the testosterone-aggression relationship in this population. PMID- 7982869 TI - Prediction of response to methylphenidate among children with ADHD and mental retardation. AB - OBJECTIVE: The primary purpose of this study was to predict stimulant medication response among children with attention-deficit hyperactivity disorder (ADHD) and mental retardation (MR). METHOD: Forty-seven children with ADHD and MR (IQs of 48 to 77) served as subjects; ages ranged from 6.1 to 12.5 years. Subjects participated in a double-blind, placebo-controlled study of two doses of methylphenidate (0.3 and 0.6 mg/kg per dose) and a placebo. Data were collected in each child's weekday classroom and a Saturday laboratory classroom. Stepwise multiple regression analyses were used to predict drug responses in both settings. RESULTS: Higher parent ratings of impulsivity and activity level at baseline were associated with greater gains in weekday classroom dependent measures. Similarly, higher weekday teacher measures of activity level, impulsivity, inattention, and conduct problems at baseline were related to improvement on Saturday laboratory classroom dependent measures. Finally, gender, race, and socioeconomic status (SES) were found to be important predictors, with males, Caucasian subjects, and subjects from families of higher SES more likely to evidence clinical gains on a number of variables than other subjects. CONCLUSION: These results were generally consistent with research conducted among children with ADHD but without MR. However, factors such as race and conduct problems appear to have predictive utility specific to children with MR. PMID- 7982870 TI - Secondary prevention of childhood firesetting. AB - OBJECTIVE: The Juvenile Fire Awareness and Intervention Program was established to develop and evaluate an intervention to be offered by fire fighters for children who set fires. METHOD: One hundred thirty-eight children, aged 5 to 16 years, with a history of firesetting participated in a randomized, controlled trial. The intervention involved education about fire safety and a behavior modification program designed to extinguish the desire to set fires through satiation. The frequency and severity of firesetting were recorded for 12 months after the intervention to measure outcome. RESULTS: There was a significant decrease in the frequency and severity of firesetting across all groups, with no additional improvement resulting from participation in the fire fighters' intervention. CONCLUSIONS: There is no evidence to suggest that the multicomponent program offered by trained fire fighters is effective in reducing firesetting. The marked reduction in firesetting across all groups suggests that fire safety education by the fire fighters is the most appropriate approach to this serious community problem. PMID- 7982871 TI - Tricyclic antidepressant treatment of children with ADHD and tic disorders. PMID- 7982872 TI - The case of the education summit. PMID- 7982873 TI - Is abuse a risk factor for suicide? PMID- 7982874 TI - Grand rounds: schizophrenia or bipolar? PMID- 7982875 TI - Extended-release clonidine for sleep disorders. PMID- 7982876 TI - Lipid mediators and protein kinase C activation for the intracellular signaling network. AB - Upon stimulation of a cell surface receptor, a membrane phospholipid degradation cascade is often induced through the activation of several phospholipases, yielding various lipid metabolites such as diacylglycerol, free fatty acids, lysophospholipids and phosphatidic acid. Several isoforms of protein kinase C are each activated distinctly by various combinations of the lipid metabolites, presumably in different subcellular compartments. The pivotal role of this enzyme family in the intracellular signaling network is beginning to emerge. PMID- 7982877 TI - Minimum number of water molecules required for inclusion of d-limonene in the cyclodextrin cavity. AB - The ratios of inclusion of d-limonene in alpha-, beta-, and gamma-cyclodextrin (CD) cavities were measured under low moisture conditions by a micro-aqueous method, and the minimum numbers of water molecules required for inclusion of d limonene in alpha-, beta-, and gamma-CD cavities were determined by the auto catalytic inclusion model. The minimum number of water molecules required for alpha-, beta-, and gamma-CD inclusion calculated from the proposed model were comparable with that in the CD cavity in the crystal state. The effect of ethanol upon the inclusion process was investigated, particularly with a low water content. This is the first study involving measurement of the minimum number of water molecules required for the inclusion of organic molecules (d-limonene) in the CD cavity. PMID- 7982878 TI - Lanthanide ions for the first non-enzymatic formation of adenosine 3',5'-cyclic monophosphate from adenosine triphosphate under physiological conditions. AB - Adenosine 3',5'-cyclic monophosphate (cAMP) is formed from adenosine triphosphate at pH 8 and 50 degrees C by use of lanthanide ions. Pr3+ and La3+ are the most active. The cAMP formation is more efficient at higher pH, where the mixture is made homogeneous by the addition of beta-cyclodextrin. The potential functioning of lanthanide ions as the catalytic center of an artificial adenylate cyclase is indicated. PMID- 7982879 TI - Changes in microsomal lysophospholipid acyltransferase activity are correlated with rat parotid gland enlargement induced by chronic administration of isoproterenol. AB - Chronic (5- and 10-day) administration of isoproterenol, an agent that induces the proliferation of salivary gland cells, produced increases in microsomal 1 acyl-sn-glycero-3-phosphate acyltransferase and 1-acyl-sn-glycero-3 phosphocholine acyltransferase activity in rat parotid glands in parallel with gland enlargement. This increased activity was reduced when the treatment was stopped, the reduction corresponding to the reduction in gland weight. There were significant correlations between lysophospholipid acyltransferase activity and gland weight, and between the activities of the two types of lysophospholipid acyltransferase. However, isoproterenol treatment did not affect any of the steps of the subsequent phospholipid N-methylation. These results suggest that the cell proliferation induced by chronic administration of isoproterenol in the parotid gland is accompanied by reversible and selective increases in microsomal lysophospholipid acyltransferases. PMID- 7982880 TI - Specific immunization using keyhole limpet hemocyanin-ganglioside conjugates. AB - In a search for adjuvants of non-bacterial origin for immunization with ganglioside, we investigated whether chemical coupling to immune stimulatory protein could increase the immunogenicity of sialoglycosphingolipid. A novel method for the linkage of glycosphingolipids, including gangliosides, to protein was established. The procedure includes lysis of the sphingoid double bond by ozone, reduction of the ozonolysis product to the aldehyde, and coupling to amino groups, either directly by reductamination, or by conjugation via a long aliphatic chain dicarboxylic acid linker. Using this method, gangliosides Gfpt1 (IV2-Fuc-, II3NeuAc-Gg4Cer), Glac2 [II3(NeuAc)2-LacCer], and Gtet1 (II3NeuAc Gg4Cer) were coupled to keyhole limpet hemocyanin (KLH), and the immunogenicity of the conjugates was tested. Immunization of mice with the KLH-ganglioside conjugates led in each case to the formation of IgG- and IgM antibodies that recognized the underivatized gangliosides, respectively. In contrast to this, mixtures of KLH and ganglioside proved ineffective for immunization. KLH-tumor associated ganglioside conjugates may, therefore, be considered as possible vaccines in immune therapy of cancer. PMID- 7982881 TI - Conformational changes of proteins at an interface induced by a supported planar phosphatidic acid monolayer. AB - Conformational changes of two types of proteins, water-soluble proteins (BSA and myoglobin) and membrane-associated protein (cytochrome c), induced by a negatively charged supported planar phospholipid monolayer were studied. The water-soluble proteins lost most of their ordered secondary structure and formed a random conformation in the initial stage of adsorption, and but in the later stage they retained more of the alpha-helical structure which was their main native secondary structure in solution. The membrane-associated protein, cytochrome c, showed a different conformational change in the adsorption process. In the initial stage, it showed an increase in beta-structures but not random coils. In the later stage, it contained more alpha-helixes than that in solution. PMID- 7982882 TI - Self-assembling process of cylindrical virus coat proteins as observed by synchrotron small-angle X-ray scattering. AB - The self-assembly process of cucumber green mottle mosaic virus (CGMMV) protein and tobacco mosaic virus (TMV) protein was examined by the thermodynamic analysis of small-angle X-ray scattering (SAXS) data. Each polymerization step of the coat proteins was assumed to be specified by a single equilibrium constant, and the equilibrium constant was evaluated by fitting the size and shape of the constituents observed by SAXS to those calculated from an assumed polymerization scheme. The logarithmic plots of the equilibrium constant against the inverse of temperature were fitted with a straight line at each buffer concentration and the thermodynamic quantities were evaluated from its intercept (yielding entropy) and slope (yielding enthalpy). The enthalpy and entropy values of TMV protein were found to be independent of buffer concentration, whereas those of CGMMV protein depended strongly on buffer concentration. In the limit, as ionic strength tends to infinity, both the enthalpy and entropy values of CGMMV protein approach those of TMV protein. The higher negative surface charge of CGMMV protein is considered to be responsible for the formation of stable single-layered disks, and for the slow polymerization process even at higher temperature and higher buffer concentrations. PMID- 7982883 TI - Post-translational import of 3-ketoacyl-CoA thiolase into rat liver peroxisomes in vitro. AB - Cell-free translation products of hepatic free polysomal RNA from a clofibrate treated rat were incubated at 26 degrees C for 0-60 min with a post-heavy mitochondrial supernatant fraction from normal rat liver. Exogenously added proteinase K-resistant precursor and mature forms of peroxisomal 3-ketoacyl-CoA thiolase were recovered in a particulate fraction and increased with time. Both forms of thiolase cosedimented with peroxisomes, when the proteinase K-treated import reaction mixture was centrifuged in a sucrose density gradient. The in vitro import and processing of thiolase precursors, types A and B, was likewise reproduced with highly purified peroxisomes. These results strongly suggest that the precursor form of 3-ketoacyl-CoA thiolase is translocated into peroxisomes, apparently without tight coupling with proteolytic processing to the mature protein. PMID- 7982884 TI - Dexamethasone induces the GLUT4 glucose transporter, and responses of glucose transport to norepinephrine and insulin in primary cultures of brown adipocytes. AB - Glucose uptake into brown adipose tissue is enhanced directly by norepinephrine released from the sympathetic nerves. In the present study, we tried to establish culture conditions for brown adipocytes which are favorable for investigation of this unique glucose transport. Stromal-vascular cells isolated from the interscapular brown adipose tissue of newborn rats differentiated into brown adipocytes expressing the uncoupling protein, when the cells were maintained on collagen-coated dishes. These cells, however, did not show an increase in 2 [3H]deoxyglucose transport in response to insulin or norepinephrine, nor did they exhibit expression of the GLUT4 glucose transporter, whereas GLUT1 was present, as judged on Western blotting. Pre-treatment of confluent cells with dexamethasone induced a response of glucose transport to either insulin or norepinephrine, and the expression of GLUT4, together with notable accumulation of lipid droplets. The induction of GLUT4 expression by dexamethasone was dose dependent and potentiated by insulin. These results indicate that treatment of cultured brown adipocytes with dexamethasone makes it feasible to analyze the mechanism underlying the enhancement of glucose transport induced by norepinephrine. PMID- 7982885 TI - Inactivation of Ca2+/calmodulin-dependent protein kinase II by Ca2+/calmodulin. AB - Incubation of calmodulin-dependent protein kinase II with Ca2+ and calmodulin resulted in a marked inactivation of the enzyme. Chelation of Ca2+ by EGTA or addition of calmodulin antagonists, W-7 or trifluoperazine, completely blocked this inactivation. The concentration required for the half-maximal inactivation, 127 microM, is three to four orders of magnitude higher than that for the half maximal activation of the enzyme. The Ca2+/calmodulin-independent activity of the proteolytic fragment of the enzyme, whose calmodulin-binding site involved in the enzyme activation was deleted, was also decreased by incubation with Ca2+ and calmodulin. These results suggest that calmodulin-dependent protein kinase II possesses a second, low-affinity calmodulin-binding site, which is distinct from the calmodulin-binding site involved in the activation of the enzyme, and that the binding of calmodulin to the second binding site causes the inactivation of the enzyme. The inactivation by Ca2+/calmodulin was temperature-dependent. The addition of both 500 microM ADP and 10 mM MgCl2 markedly protected the enzyme against the inactivation, while such a marked protection was not observed after the addition of either of the two alone. The addition of 5 microM autocamtide-2, a synthetic substrate peptide containing the amino acid sequence of the autophosphorylation site (Thr286/Thr287 in alpha/beta, gamma, and delta isoforms) lying within the autoinhibitory domain, also protected the enzyme against the inactivation by Ca2+/calmodulin, while syntide-2, another synthetic substrate peptide corresponding to a phosphorylation site of glycogen synthase, did not protect it even at a concentration as high as 304 microM. PMID- 7982886 TI - pH profile of kinetic constants of RNase Rh from Rhizopus niveus and its mutant enzymes towards UpU, and possible mechanisms of RNase Rh. AB - In order to elucidate the mechanism of action of Rhizopus niveus RNase Rh, we investigated the pH profiles of the kinetic parameters of RNase RNAP Rh, a derivative of RNase Rh, and its mutant enzymes, i.e., RNase RNAP Rh H104F, RNase RNAP Rh E105Q, and RNase RNAP Rh D51N. Based on comparisons of their profiles we concluded that protonation of His104 is indispensable for the enzymatic activity and Glu105 accelerates the enzymatic activity, especially at acid pH centered at pH 3.5. Based on these data and the previous data on the chemical modification and enzymatic properties of other mutant enzymes, we propose the following as a possible mechanisms of RNase Rh action. (i) His109 participates in enzymatic action as a general base catalyst which removes the hydrogen of the 2'-OH of the ribose moiety. (ii) His46 participates in the reaction as a general acid catalyst which interacts with the 5'-oxygen atom of the scissile phosphodiester bond and becomes a proton donor to the departing nucleoside or nucleotide. (iii) His104 interacts with phosphate anion and its protonation is favorable for the enzymatic activity. (iv) Since the protonated form of Glu105 is more favorable for activity, we postulate two possible roles for Glu105: (a) its stabilizes the intermediate, and (b) it interacts with the oxygen atom of P = O and polarizes the phosphorus atom. PMID- 7982887 TI - Mapping and characterization of a retinoic acid-responsive enhancer of midkine, a novel heparin-binding growth/differentiation factor with neurotrophic activity. AB - MK is a gene that is activated by retinoic acid in embryonal carcinoma (EC) cells and is expressed temporarily during the mid-gestation period of mouse embryogenesis. Midkine, the product of the gene is a novel heparin-binding growth/differentiation factor with neurite outgrowth and neurotrophic activities. The regulatory DNA element in the retinoic acid-induced expression of the MK gene has been investigated. The 1.9 kb 5'-flanking region of the MK gene can mediate retinoic acid-responsive gene expression in F9 and HM-1 EC cells. Analysis of this region by deletion mutagenesis in F9 EC cells shows that there is a retinoic acid-responsive enhancer (designated as REM1) around 900 bp upstream from the transcription start site. This enhancer is composed of two sequence elements, which are located between -1006 and -895 and between -901 and -794. The core element of the upstream region (-971 to -955), whose deletion abolished the retinoic acid responsiveness, contained a sequence highly homologous to a binding site for retinoic acid receptors. Binding of a retinoic acid receptor heterodimer to this core element was verified by gel shift assay. Thus, retinoic acid and the receptor complex can directly induce the expression of a growth/differentiation factor gene. PMID- 7982888 TI - Improved purification of arylsulfate sulfotransferase from human intestinal bacterium by using polyclonal antibody. AB - Arylsulfate sulfotransferase (ASST) from a human intestinal bacterium stoichiometrically catalyzed the transfer of the sulfate group of phenylsulfate esters to phenolic compounds. Polyclonal antibodies against ASST were obtained from rabbit sera. These antisera did not inhibit ASST activity. ASST was recognized by the IgG fraction of the antisera, but rat liver phenol sulfotransferase did not show cross-reactivity to ASST on Western blot (immunoblot) analysis. The ASST was purified by an anti-ASST immobilized affinity column chromatography to homogeneity on SDS-PAGE. The NH2-terminal amino acid and partial sequence of the purified enzyme were serine and SVKYSFEDHIINRQYEAEQAMLAKF, respectively. We corrected the previous result that the NH2-terminal of ASST was arginine. PMID- 7982889 TI - Molecular cloning and sequence analysis of cDNA coding for the precursor of the human salivary proline-rich peptide P-B. AB - cDNA coding for the human salivary proline-rich peptide P-B was amplified by polymerase chain reaction using human submaxillary gland cDNA as the template and d(deoxy)T25 as the primer for both strands. The amplified cDNA of 0.8 kbp encodes a hydrophobic signal sequence of 22 amino acid residues and the complete sequence of P-B (57 amino acids). The determined nucleotide sequence of P-B cDNA indicates that P-B is a mature full-size protein and not the enzymic degradation product of a larger protein. The gene coding for P-B is not a member of the proline-rich protein gene family characterized previously. PMID- 7982890 TI - Design of variants of the second domain of urinary trypsin inhibitor (R-020) with increased factor Xa inhibitory activity. AB - The second domain (R-020) of human urinary trypsin inhibitor (UTI) exerts similar inhibitory activities on trypsin, alpha-chymotrypsin, leukocyte elastase, and plasmin to those of UTI itself, and additionally inhibits coagulation factor Xa (FXa) and plasma kallikrein, on both of which UTI has no inhibitory effect. In the present study, we attempted to increase this FXa-inhibitory activity by modeling the structure of R-020-FXa complex and substituting one or two amino acids in R-020 using recombinant DNA technology. Molecular modeling of R-020 and FXa was performed with reference to X-ray analysis of the complex of bovine pancreatic trypsin inhibitor (BPTI) and bovine trypsin to determine the site of amino acid modification. The expression plasmids into which R-020 genes with base substitution were inserted were prepared and introduced into Escherichia coli to express R-020 variants. The resulting variants were purified and their enzyme inhibitory activities were measured. The FXa-inhibitory activity was increased in four variants with single amino acid substitution. With another four variants having two amino acid substitutions involving combinations of the above single amino acid substitutions, the FXa-inhibitory activity was further increased. Because the electrostatic interaction within R-020-FXa complex seemed stronger in these R-020 variants, this increase in FXa-inhibitory effect was speculated to be a consequence of more potent binding between the enzyme and the inhibitor. PMID- 7982891 TI - Autoregulation of transcription of the hupA gene in Escherichia coli: evidence for steric hindrance of the functional promoter domains induced by HU. AB - The molecular mechanism of autoregulation of expression of the hupA gene in Escherichia coli was examined. The promoter of the gene contains a palindromic sequence with the potential to form a cruciform DNA structure in which the -35 sequence lies at the base of the stem and the -10 sequence forms a single stranded loop. An artificial promoter lacking the palindrome, which was constructed by replacing a 10 nucleotide repeat for the predicted cruciform arm by a sequence in the opposite orientation, was not subject to HU-repression. DNA relaxation induced by deleting HU proteins and/or inhibiting DNA gyrase in cells results in increased expression from the hupA promoter. We propose that initiation of transcription of the hupA gene is negatively regulated by steric hindrance of the functional promoter domains for formation of the cruciform configuration, which is facilitated at least in part by negative supercoiling of the hupA promoter DNA region. The promoter region of the hupB gene also contains a palindromic sequence that can assume a cruciform configuration. Negative regulation of this gene by HU proteins may occur by a mechanism similar to that operating for the hupA gene. PMID- 7982892 TI - Epitope mapping of bovine serum albumin using monoclonal antibodies coupled with a photoreactive crosslinker. AB - Antigenic determinants (epitopes) on bovine serum albumin (BSA) to anti-BSA monoclonal antibodies (mAbs) were assessed by means of photoaffinity labeling. Anti-BSA mAbs, AB3 and AB6, were modified with an 125I-labeled photoreactive crosslinker, sulfosuccinimidyl 2-(p-azidosalicylamido)ethyl-1,3'-dithiopropionate (SASD) and then bound with BSA. The complex yielded was irradiated with UV light to facilitate covalent binding of the modified mAb with BSA. Reduction of the product with 2-mercaptoethanol revealed that radioactivity of 125I-SASD was specifically introduced into BSA, probably near the mAb combining site(s). The radiolabeled or native BSA was digested with V8 protease and the peptides produced were assessed for their amino acid sequence, the radiolabeled amino acids contained, and their reactivity to mAb. The results indicated that AB3 mAb recognized an epitope in the region of Ala-537 to Asp-554 on a linear part of the BSA molecule, whereas AB6 mAb probably recognized an epitope of the assembled form present in a peptide of Asp-299 to Glu-338. PMID- 7982893 TI - Glutathione S-transferases in rat testis microsomes: comparison with liver transferase. AB - Glutathione S-transferases in testis microsomes were purified from rats and compared with the liver microsomal transferase. When microsomal fractions were prepared from rat testis by the same method as used for liver microsomes, testis microsomal glutathione S-transferase activity was increased 2-fold by N ethylmaleimide as compared to a 7-fold increase in that of the liver transferase. In contrast to the single glutathione S-transferase in liver microsomes, at least three isozymes of glutathione S-transferase were separated from testis microsomes on hydroxylapatite column chromatography. The major fraction exhibiting glutathione S-transferase activity from the testis microsomes was shown to contain a member of the Mu family. The second fraction with transferase activity contained one of the Alpha class, and the third and smallest fraction was found to contain the liver microsomal form of glutathione S-transferase. Since the GSH S-transferase of the Mu family is present in the cytosol, we isolated the GSH S transferase from testis cytosol, it being suggested that the major GSH S transferase in testis microsomes is the cytosolic transferase. These results indicate that testis microsomes contain mainly the cytosolic form of glutathione S-transferase, and that the activity of the liver microsomal form of the transferase is very low. PMID- 7982894 TI - Enhancement of serine-sensitivity by a gene encoding rhodanese-like protein in Escherichia coli. AB - When cells of Escherichia coli are grown on lactate (or other carbon sources), an addition of serine to the medium causes growth inhibition. This growth inhibition is caused by inhibition by serine of homoserine dehydrogenase I, which is involved in threonine-isoleucine biosynthesis [Hama, H., Sumita, Y., Kakutani, Y., Tsuda, M., & Tsuchiya, T. (1990) Biochem. Biophys. Res. Commun. 168, 1211 1216]. We have cloned and sequenced genes which enhance the serine-sensitivity. Two open reading frames were found and designated as sseA and sseB. Introduction of either sseA or sseB gene, or both, into E. coli cells enhanced the serine sensitivity. The sseA gene elicited stronger enhancement than sseB. The deduced amino acid sequence of SseA showed considerable similarity with that of bovine liver rhodanese, which catalyzes sulfur transfer from thiosulfate. We observed a twofold increase in rhodanese activity in E. coli cells harboring a plasmid carrying the sseA gene. The position of sseA in the genetic map is around 52'. However, sseA is different from cysM, which codes for O-acetylserine sulfhydrylase-B, an enzyme catalyzing sulfur transfer from thiosulfate to O acetylserine, the map position of which is also around 52'. PMID- 7982895 TI - One- and two-electron reduction of quinones by rat liver subcellular fractions. AB - NAD(P)H-quinone (menadione, Trolox C quinone, and alpha-tocopherol quinone) reductase activity of rat liver subcellular fractions was observed optically at 340-400 nm, and oxygen radical generation was demonstrated using the ESR spin trap, 5,5'-dimethyl-1-pyrroline-1-oxide. NAD(P)H-menadione reductase activity of the fractions decreased in the order: cytosol > microsomes > plasma membranes. Although more than 65% of the activity of microsomes and plasma membranes was inhibited on the addition of dicoumarol, no change in the menadione-mediated formation of oxygen radicals by either fraction was observed. As judged from the intensity of ESR signals, the menadione-mediated oxygen radical formation by plasma membranes was only one-tenth as great as that by microsomes. No generation of oxygen radicals in the NAD(P)H-menadione reductase reaction by cytosol was found, and the activity was abolished in the presence of dicoumarol, an inhibitor of DT-diaphorase. It is concluded that plasma membranes reduce quinones by way of two-electron transfer and that the activity may prevent cellular quinone toxicity. NAD(P)H-alpha-tocopherol quinone reductase activity was confirmed in all cellular fractions [Hayashi et al. (1992) Biochem. Pharmacol. 44, 489-493] and this activity was also inhibited by dicoumarol, suggesting that it was due to DT-diaphorase. PMID- 7982896 TI - Structure and function of mannan-binding proteins isolated from human liver and serum. AB - Mannan-binding proteins (MBPs) occur in two forms, both of which are synthesized in the liver. Although two different MBP cDNAs have been cloned and characterized for rat and mouse, only one form of human MBP cDNA has been isolated. In this study, two forms of human MBP, liver MBP (L-MBP) and serum MBP (S-MBP), were purified from liver and serum and characterized, respectively. The amino acid sequences of these two human MBPs were identical and consistent with those deduced from the cDNA sequence. The most significant difference between L-MBP and S-MBP was the number of subunits, which was about 9 in L-MBP and 18 in S-MBP. Furthermore, S-MBP but not L-MBP had the ability to activate the complement. These results suggested that a newly synthesized protein is processed post translationally into two forms, S-MBP and L-MBP, in human liver. Recombinant MBP synthesized in COS-1 cells, after transfection with human MBP cDNA, was secreted into the medium, suggesting that COS-1 cells lack a mechanism for differentiating S-MBP and L-MBP. A mutant MBP synthesized in COS-1 cells which lacked a sequence comprising 9 amino acid residues at the beginning of the collagen-like domain had no ability to activate the complement, suggesting that this sequence plays an important role in the activation of the complement by human MBP. PMID- 7982897 TI - Expression and characterization of the bovine histamine H1 receptor in cDNA transfected C6 astroglioma cells. AB - Rat C6 astroglioma cells (C6-bH1R cells) expressing cloned bovine histamine H1 receptors were established by transfection with a vector (pEF-BOS-bH1R) which carried a 2.7-kbp EcoRI fragment of the bovine H1 receptor cDNA [Yamashita, M. et al. (1991) Proc. Natl. Acad. Sci. USA 88, 11515-11519]. The cloned bovine H1 receptor in C6-bH1R cells was characterized by three established criteria: the [3H]mepyramine binding assay, the accumulation of inositol phosphates induced by histamine, and histamine-induced elevation of intracellular Ca2+ concentration ([Ca2+]i). The accumulation of inositol phosphates induced by histamine was time- and dose-dependent. The accumulation of inositol trisphosphate was biphasic with a prompt increase to the maximal level, followed by a sustained submaximal level. The histamine-induced accumulation of inositol phosphates was suppressed by phorbol ester, but not by pertussis toxin. Results from the [3H]-mepyramine binding assay and histamine-induced elevation of [Ca2+]i were characteristic of H1 receptors. Several compounds among tricyclic antidepressants, neuroleptics, and serotonin antagonists showed affinities to the cloned bovine H1 receptor with Ki values similar to reported values. Histamine neither induced cAMP accumulation nor attenuated forskolin-induced cAMP accumulation in C6-bH1R cells. C6-bH1R cells are particularly useful for studying the H1 receptor-mediated astroglial cell functions. PMID- 7982898 TI - Properties of the Na+/H+ antiporter in Vibrio parahaemolyticus. AB - The properties of the Na+/H+ antiporter in Vibrio parahaemolyticus, a slightly halophilic bacterium, were investigated using everted membrane vesicles. It appears that at least two Na+/H+ antiporters are present, one that is pH dependent and one that is pH-independent. These two antiporters appear to correspond to the NhaA and NhaB antiporters of Escherichia coli, respectively. It seems that amiloride strongly inhibits the pH-dependent antiporter. Na+ is the best substrate for both of the two V. parahaemolyticus antiporters. Li+ is a poorer substrate and K+ is not a substrate. No K+/H+ antiport activity was detected in membrane vesicles of this organism. The Na+(Li+)/H+ antiport activity greatly increased with an increase in pH of the assay medium. pH did not affect the Km value of the Na+/H+ antiport, but it did increase the Vmax. PMID- 7982899 TI - ATP-dependent proteolysis in yeast mitochondria. AB - An ATP-dependent proteolysis system in yeast mitochondria was characterized by examining the hydrolysis of mitochondrial translation products in isolated mitochondria. Degradation of [35S]methionine-labeled polypeptides synthesized in isolated yeast mitochondria was activated by exogenously added ATP. ADP, GTP, and CTP substituted for ATP to some extent, but nonhydrolyzable ATP analogues did not. Adenosine-5'-O-(3'-thio-triphosphate) effectively competed with ATP as activator. Carboxyatractyloside, an inhibitor of adenine nucleotide translocation across the mitochondrial inner membrane, and the metal chelator o-phenanthroline inhibited the ATP-dependent proteolysis. The latter inhibition was abolished by subsequent addition of Mn2+ or Co2+ but not Ca2+ or Zn2+. Hemin inhibited the ATP dependent proteolysis of mitochondrial translation products with a half-maximum inhibition at 12 microM. Analysis by SDS-polyacrylamide gel electrophoresis showed that [35S]methionine-labeled polypeptides were rapidly degraded into low molecular-weight species. Submitochondrial particles retained the ATP-dependent proteolytic activity and had the same spectrum of inhibitors as intact mitochondria except for a reduced effect of carboxyatractyloside. These results indicate that yeast mitochondria contain an ATP-dependent and hemin-sensitive proteolysis system which is associated with the inner membrane and can hydrolyze mitochondrial translation products, and that a chelator-sensitive protease is probably involved in this system. PMID- 7982900 TI - Human aldolase C: characterization of the recombinant enzyme expressed in Escherichia coli. AB - To study the structure/function relationship and enzymatic properties of human aldolase C, we have constructed an Escherichia coli expression plasmid, pHAC11, for the isozyme. E. coli cells carrying this plasmid produced enzymatically active human aldolase C. The kcat and Km values for fructose-1,6-bisphosphate (Fru-1,6-P2) and fructose-1-phosphate (Fru-1-P) of the recombinant enzyme were found to be similar to those of authentic aldolase C from human brain. The Fru 1,6-P2/Fru-1-P activity ratio of the recombinant enzyme is approximately 13.5, which is comparable to that of the recombinant rat aldolase C, but is slightly higher than those of rat brain and hepatoma aldolases C. The substitution of Ser for the carboxyl-terminal Tyr (Tyr-363) of the recombinant enzyme caused a marked decrease in that of Fru-1,6-P2, with little change in that of Fru-1-P. The activity ratio changed from 13.5 for the normal enzyme to 3.8 for the engineered enzyme. Human aldolase C was found to form tetrameric hybrids with aldolase B in vivo when these enzymes were coexpressed in E. coli cells. PMID- 7982901 TI - Calpain-calpastatin interactions in epidermoid carcinoma KB cells. AB - We examined the activation of mu-calpain in human epidermoid carcinoma KB cells following a rise in intracellular calcium concentration using antibodies specifically recognizing different activation states of mu-calpain. KB cells possess calpastatin activity in large excess of calpain activity as analyzed by ion exchange HPLC. Stimulation of the cells with a calcium ionophore, ionomycin, caused production of the autolytic intermediate form (M(r) = 78 k) of mu-calpain derived from the preautolysis form (80 k), while the fully autolyzed postautolysis form (76 k) remained below detectable levels at all times. The appearance of the autolytic intermediate paralleled limited proteolysis of the membrane-associated calpastatin fractions (110 k and 106 k); the resulting fragments (68 k and 45 k) were released into the cytosol. Both the production of the autolytic mu-calpain intermediate and the limited proteolysis of calpastatin in cell lysates in the presence of calcium were inhibited by a synthetic calpastatin peptide, indicating that proteolysis of calpastatin was indeed catalyzed by calpain and that the autolytic intermediate may have exerted the proteolytic activity. Furthermore, mu-calpain autolysis and calpastatin degradation, upon ionomycin treatment, were both augmented by epidermal growth factor (EGF). These results suggest that calpastatin serves not only as an inhibitor but also as a substrate for calpain at cell membranes and that intracellular conditions associated with the cell cycle may affect the activation of mu-calpain. PMID- 7982902 TI - Transcriptional attenuation and differential mRNA stability in the regulation of the Escherichia coli melibiose operon. AB - The organization of the melibiose operon of Escherichia coli is promoter-melA melB. The amount of the product (alpha-galactosidase) of the first gene (melA) is much larger than that of the product (melibiose permease) of the second gene (melB). Using the chloramphenicol acetyltransferase gene (cat) as reporter, we found that there was an element between melA and melB, which reduced the expression of the downstream gene, melB. This region contained a boxA-like sequence, which is known as a binding site for an attenuation factor, NusA. Northern hybridization analysis revealed that the ratio of melA mRNA and melAB mRNA was comparable with the ratio of the melA and melB products. We also found that the melA mRNA was about 3-fold more stable than the melAB mRNA. Experimental results obtained with a nusAts mutant suggested that the NusA protein is involved in the reduced expression of the melB gene. We conclude that the production ratio of alpha-galactosidase and melibiose permease is regulated at two levels: 1) transcription and 2) mRNA stability. PMID- 7982904 TI - Retinoic acid-induced gene expression of tissue transglutaminase via protein kinase C-dependent pathway in mouse peritoneal macrophages. AB - Culture of mouse resident peritoneal macrophages with retinoic acid resulted in increased expression of the tissue transglutaminase gene as revealed by increases in the maximal velocity of the enzyme reaction in the cytosol and in the enzyme mRNA level. Protein kinase C-activating phorbol esters and okadaic acid, both of which were without effect on the enzyme induction by themselves, enhanced the retinoic acid-induced gene expression, which was in turn inhibited partially by pertussis toxin and totally by inhibitors of protein kinase C in either the presence or absence of phorbol esters. Retinoic acid was more effective in the "conditioned" medium, in which macrophages had been cultured for a time longer than 4 h, than in the "fresh" medium. The retinoic acid induction of transglutaminase was accompanied by increased phosphatidylinositol turnover and phosphatidic acid generation, which were efficiently suppressed by prior exposure of cells to pertussis toxin. It is likely that certain autocrine factor(s) liberated during culture of macrophages may afford conditions favorable for retinoic acid-induced gene expression, presumably via pertussis toxin-sensitive G protein-mediated phosphoinositide metabolism leading to activation of protein kinase C. PMID- 7982903 TI - Trinitrophenylation of the reactive lysine residue in double-headed myosin in the presence of PP. AB - Lys-83 in the heavy chain of rabbit skeletal muscle myosin is rapidly and stoichiometrically modified by trinitrobenzene sulfonate. Other authors claimed that the half-stoichiometric trinitrophenylation of Lys-83 in myosin in the presence of PPi was correlated to a Pro/Ser microheterogeneity at the 78th residue position in the heavy chain [Miyanishi, T., Maita, T., Matsuda, G., & Tonomura, Y. (1982) J. Biochem. 91, 1845-1853]. However, our recent studies with chymotryptic subfragment 1 (S1) instead of myosin showed no such correlation between the half-stoichiometric trinitrophenylation and the Pro/Ser microheterogeneity [Komatsu, H. & Tawada, K. (1993) J. Biol. Chem. 268, 16974 16978]. Since the global structure of the head portion of myosin is different from that of chymotryptic S1 that lacks DTNB light chain, it could be argued that the difference is due to the structural difference between chymotryptic S1 and myosin. We hence reexamined the situation with myosin, and obtained the same results as found with S1: (i) Lys-83 in myosin was half-stoichiometrically trinitrophenylated in the presence of PPi, although it was stoichiometrically modified in the absence of PPi; (ii) there was a Pro/Ser microheterogeneity at the 78th position in the myosin heavy chain, which was not correlated to the half stoichiometric trinitrophenylation of Lys-83 in the presence of PPi. PMID- 7982905 TI - Peroxisomal biogenesis: multiple pathways of protein import. PMID- 7982906 TI - Physical interaction of the HIV-1 Nef protein with beta-COP, a component of non clathrin-coated vesicles essential for membrane traffic. AB - Nef is a 27-kDa myristylated protein conserved in most human immunodeficiency virus (HIV)-1, HIV-2, and simian immunodeficiency virus isolates. Simian immunodeficiency virus Nef is required in macaques for both high viral load and full pathological effects. Nef down-regulates the cell surface expression of CD4 by a post-translational mechanism that is not yet fully elucidated. We have used the yeast two-hybrid system to identify cellular proteins that interact with Nef. A cDNA was isolated which encodes a COOH-terminal fragment of human beta-COP, a major coat component of non-clathrin-coated vesicles. Nef and beta-COP interacted in vitro and were found to be physically associated in HIV-1-infected cells by co immunoprecipitation. These observations suggest that beta-COP might be one of the cellular mediators of Nef function in HIV-1-infected cells. PMID- 7982907 TI - CD28 signaling causes a sustained down-regulation of I kappa B alpha which can be prevented by the immunosuppressant rapamycin. AB - CD28, an important T cell surface molecule, mediates a costimulatory signal in the activation of T cell immune responses. CD28 signaling is resistant to the immunosuppressant cyclosporin A (CsA) but sensitive to the immunosuppressant rapamycin. CD28 costimulation induces transcription from the interleukin (IL)-2 promoter via the CD28 response element. The levels of c-Rel, a CD28 response element-binding factor, were found previously to be increased by CD28 costimulation. Therefore, we focused our present study on the mechanism(s) of c Rel up-regulation by CD28 signaling in Jurkat T cells. In this paper, we showed that CD28 costimulation accelerated the kinetics of nuclear translocation of c Rel. We showed that CD28 signaling, distinct from other stimuli such as phorbol 12-myristate 13-acetate, IL-1, and tumor necrosis factor-alpha, caused a sustained down-regulation of the inhibitor I kappa B alpha in Jurkat T cells. However, the levels of two other c-Rel inhibitors, namely NFKB1 (p105) and NFKB2 (p100), were not affected. Remarkably, the CD28-mediated down-regulation of I kappa B alpha was prevented by rapamycin but not by CsA. The counter-regulation of I kappa B alpha by CD28 signaling and rapamycin observed in Jurkat T cells is also reproducible in primary T cells. In contrast, the phorbol 12-myristate 13 acetate/ionomycin-mediated down-regulation of I kappa B alpha was prevented by CsA but not by rapamycin. Our data suggest that I kappa B alpha is the down stream target of both CD28 signaling and rapamycin; a continued down-regulation of I kappa B alpha by CD28 costimulation leads to enhanced nuclear translocation of c-Rel, which in turn causes a sustained up-regulation of IL-2 gene expression. PMID- 7982908 TI - Phosphorylation of NF-KB1-p50 is involved in NF-kappa B activation and stable DNA binding. AB - We have previously shown that NF-kappa B/Rel family members are physically associated phosphoproteins, and p105 and p50 are hyperphosphorylated after NF kappa B activation. In this report, we further studied the phosphorylation involved in NF-kappa B activation in Jurkat T cells responding to phorbol 12 myristate 13-acetate and phytohemagglutinin. Immediately following stimulation, p50 is hyperphosphorylated, and a phosphorylated form of p50 (pp50) is translocated from the cytoplasm to the nucleus. The kinetics of this nuclear translocation paralleled that of the appearance of an active kappa B DNA-binding complex. An at least 30-fold higher level of kappa B DNA binding was detected in pp50 than p50. The enhanced binding could be attributed to a much greater stability detected in the complex consisting of kappa B DNA and pp50, but not p50. These results suggest that phosphorylation of p50, and perhaps other family members as well, may be involved in the activation of NF-kappa B/Rel family transcription factors. PMID- 7982909 TI - A "molten globule" of Torpedo acetylcholinesterase undergoes thiol-disulfide exchange. AB - Torpedo acetylcholinesterase is a disulfide-linked homodimer containing three intramolecular disulfide bonds, as well as a single free thiol on Cys-231. We report that in a "molten globule" state, produced by 1.5 M guanidine hydrochloride, this enzyme undergoes rapid intramolecular thiol-disulfide exchange, in the absence of reducing agents, resulting in the production of novel species. Most strikingly, this results in appearance of enzyme monomers. Chemical modification of the free thiol group prevents these changes. Unfolded acetylcholinesterase, namely in 5 M guanidine hydrochloride, also undergoes intramolecular thiol-disulfide exchange, including production of enzyme monomers, but at a much lower rate. Our data show that the molten globule state, in contrast to the native and unfolded states, is both compact and flexible, thus being especially amenable to thiol-disulfide exchange. PMID- 7982910 TI - Up-regulation of the plasma membrane oxidoreductase as a prerequisite for the viability of human Namalwa rho 0 cells. AB - We have studied aspects of the regulatory interrelationship between the plasma membrane oxidoreductase (PMOR) system and the mitochondrial respiratory capacity of human Namalwa cells. Although the role of mitochondria in the maintenance of cellular redox and energetic states is well established, the PMOR system in comparison is a poorly characterized enzyme system whose functions, particularly in relation to cellular metabolism, have not been clearly elucidated. Therefore we compared the PMOR and mitochondrial respiratory activities of human Namalwa cells during the induction by ethidium bromide treatment of rho 0 cells, which lack a functional mitochondrial respiratory system. The plasma membrane NADH ferricyanide reductase activity of the PMOR system was found to increase in a stepwise manner concomitant with a decline in cellular mitochondrial respiratory activity. Addition of p-chloromercuriphenylsulfonic acid to the culture medium, at a concentration totally inhibiting the plasma membrane NADH-ferricyanide reductase in vitro, leads to cell death of rho 0 but not of rho + cells. Thus, the up-regulation of a functional PMOR system is a necessary phenomenon in maintaining the viability of mammalian rho 0 cells. PMID- 7982911 TI - Initiation of transcription by RNA polymerase II is limited by melting of the promoter DNA in the region immediately upstream of the initiation site. AB - To further elucidate the mechanism of transcriptional initiation, we used synthetic oligonucleotides to prepare templates containing heteroduplex regions of varying size and location along the DNA of the adenovirus major late promoter. Unlike closed, linear DNA, or DNA with a downstream mismatch, DNA with a mismatch upstream of the initiation site only required the general factors TATA box binding protein and transcription factor (TF) IIB to direct specific and accurate initiation in vitro by calf thymus RNA polymerase II. In the presence of TFIIF, initiation was possible on closed, linear DNA, but an upstream mismatch region still stimulated transcriptional initiation by more than 100-fold, leading to production of approximately 0.5 transcript/template in the absence of TFIIE, TFIIH, or ATP. The presence of a DNA mismatch was most effective in the -9 to -1 region; furthermore, stimulation by a mismatch did not require that the initiation site be included in the heteroduplex region. Efficient initiation at the immunoglobulin heavy chain promoter in the presence of TATA box-binding protein and TFIIB was also achieved when a mismatch region was introduced from -9 to +3. Our results suggest that initiation by RNA polymerase II in the absence of transcriptional activation is limited by melting of the promoter DNA upstream of the initiation site. PMID- 7982912 TI - The minimal fragments of c-Raf-1 and NF1 that can suppress v-Ha-Ras-induced malignant phenotype. AB - v-Ha-Ras, an oncogenic Ras mutant, causes malignant transformation of mammalian cells by recruiting c-Raf-1, a cytosolic Ser/Thr kinase, to the plasma membranes/cytoskeleton. The kinase activity of c-Raf-1 resides in the C-terminal half, which activates mitogen-activated protein (MAP) kinase kinase, while it is the N-terminal half of c-Raf-1 (Raf257, residues 1-257) that binds the Ras-GTP complex and can compete Ras GTPase-activating proteins such as NF1 for binding to Ras. However, it still remains to be clarified whether overexpression of Raf257 or its minimal Ras-binding fragment alone is sufficient to suppress Ras-induced malignancy. In this paper we demonstrate for the first time that the 81-amino acid fragment (Raf81, residues 51-131), the minimal Ras-binding fragment of Raf, indeed can suppress v-Ha-Ras-induced malignant phenotype. A further deletion of the first 6 amino acids causes 65% reduction in the Ras binding of Raf81. The resultant 75 amino acid fragment (Raf75, residues 57-131) consists of a single alpha-helix, five anti-paralleled beta-sheets and five loops. We have found that a further deletion of either the first beta-sheet/loop or the last two beta sheets/loops completely abolishes Ras binding. In addition we have found that the removal of the C-terminal 35 amino acids from a Ras-binding 91-amino acid fragment of NF1 (NF91, residues 1441-1531) does not abolish its ability to suppress the Ras-induced malignancy. PMID- 7982913 TI - The 90-kDa heat shock protein is essential for Ah receptor signaling in a yeast expression system. AB - In an effort to provide a more powerful system to study the Ah receptor (AHR) signaling pathway, we expressed the AHR, its dimerization partner ARNT, and a beta-galactosidase (lacZ) reporter gene, driven by two dioxin-responsive enhancers, in the yeast Saccharomyces cerevisiae. In this system, the agonists beta-naphthoflavone and alpha-naphthoflavone induced transcription of the lacZ gene, with EC50 values of 7.9 x 10(-8) and 3.0 x 10(-7) M, respectively, while the nonagonist dexamethasone was without effect. As a first application of this system, we examined the relationship between the 90-kDa heat shock protein (hsp90) and AHR function. To accomplish this in a manner that was independent of the ARNT protein, we constructed a chimeric receptor in which the DNA binding and primary dimerization domains of the AHR were swapped with analogous domains from the LexA protein. Coexpression of this AHR-LexA chimera and a lacZ reporter gene driven by eight LexA operator sites in a yeast strain with regulatable levels of hsp90, yielded pharmacology that closely mirrored that of the AHR/ARNT/dioxin responsive enhancer system described above, but only when hsp90 levels were held near their wild type levels. When hsp90 levels were reduced to approximately 5% of normal, AHR signaling in response to agonist was completely blocked despite normal cell growth. These results provide the first genetic evidence for the role of hsp90 in AHR signaling and provide the basis for a powerful new system in which to study this pathway. PMID- 7982915 TI - Interferon-gamma- and phorbol myristate acetate-responsive elements involved in intercellular adhesion molecule-1 mRNA stabilization. AB - Treatment of cells with interferon (IFN)-gamma or phorbol myristate acetate (PMA) induces up-regulation of the level of intercellular adhesion molecule-1 (ICAM-1; CD54) mRNA by stabilization of an otherwise labile mRNA. Here, we have generated various deletion mutants of ICAM-1 and stably transfected them into the murine fibroblast Ltk- cells that express no endogenous ICAM-1 or -2 (CD102) in an effort to define the regions within ICAM-1 mRNA responsive to IFN-gamma or PMA. Induction of ICAM-1 mRNA in the transfected L cells by the treatment with IFN gamma revealed that the truncation of the region of ICAM-1 mRNA encoding the cytoplasmic domain made it non-responsive to IFN-gamma whereas all other regions were dispensable. In contrast, PMA-induced accumulation of ICAM-1 mRNA required the 3'-untranslated region (UTR). To further elucidate the role of these regions in mRNA destabilization and responsiveness to IFN-gamma and PMA, ICAM-2 mRNA that is stable and not responsive to IFN-gamma or PMA was used as a reporter gene. The putative IFN-gamma-responsive region of ICAM-1 mRNA encoding its cytoplasmic domain rendered it unstable and responsive to IFN-gamma but not PMA. Conversely, the 3'-UTR of ICAM-1 fused with ICAM-2 mRNA also made it unstable and responsive to PMA but not IFN-gamma. Half-life analysis showed that the induction of these chimeric mRNAs by IFN-gamma and PMA was due, at least in part, to the prolongation of their turnover rate. These results taken together demonstrate that two distinct regions of ICAM-1 mRNA regulate its stability, one encoding the cytoplasmic domain and responsive to IFN-gamma and the other in the 3'-UTR and responsive to PMA. PMID- 7982914 TI - Cloning and expression of the gene for group B streptococcal hyaluronate lyase. AB - Group B streptococci (GBS) are a major cause of serious human perinatal infections. Most clinical isolates of GBS secrete hyaluronate lyase, and production of high levels of the enzyme has been associated with strain virulence. Degenerate oligonucleotide primers, designed on the basis of the amino acid sequences of tryptic peptides prepared from the purified enzyme, permitted the polymerase chain reaction amplification from GBS chromosomal DNA of a 363 base pair internal DNA fragment of the GBS hyaluronate lyase gene (hylB). This DNA fragment was used as a probe to screen a lambda phage library of GBS chromosomal DNA fragments. Sequence analysis of positive clones identified an open reading frame capable of coding for a 111-kDa protein. Since no single clone was found to contain the entire gene it was necessary to reconstruct the gene from two plasmids containing inserts with suitable overlapping sequences. When this reconstructed gene was transformed into Escherichia coli, high level expression of hyaluronate lyase activity was obtained. PMID- 7982916 TI - Primary structure and differential expression during development and pregnancy of a novel voltage-gated sodium channel in the mouse. AB - Until recently, all cloned vertebrate voltage-dependent sodium channels exhibited high sequence homology to one another and appeared to comprise a single multigene subfamily. An exception is the human Nav2.1 channel proposed to represent a second Na+ channel (NaCh) gene subfamily since comparison with previously cloned voltage-gated NaChs revealed only 40-45% identity. We have now cloned a mouse NaCh (mNav2.3) from an atrial tumor cell line that shows high amino acid sequence identity to hNav2.1 in functionally relevant regions such as the pore-forming segments, S4 segments, and inactivation gate sequence. Overall sequence identity is 68%. mNav2.3 mRNA was most abundant in heart and uterus, and the transcript levels in heart, brain, and skeletal muscle were differentially regulated during development. Transcript levels in heart were greatest immediately after birth. mNav2.3 transcript levels in pregnant uterus increased 3-fold between day 15 of pregnancy and birth and then declined 15-fold during the 2 days following delivery. The mNav2.3 amino acid sequence indicates that the Nav2 NaCh gene subfamily is well conserved across species, and the tissue-specific and developmental regulation of mRNA expression suggests these channels play important physiological roles in cardiac and uterine muscle. PMID- 7982917 TI - p145, a major Grb2-binding protein in brain, is co-localized with dynamin in nerve terminals where it undergoes activity-dependent dephosphorylation. AB - Three major rat brain proteins were recently found to bind the SH3 domains of Grb2: synapsin I, dynamin, and a novel 145-kDa protein (p145) (McPherson, P. S., Czernik, A. J., Chilcote, T. J., Onofri, F., Benfenati, F., Greengard, P., Schlessinger, J., and De Camilli, P. (1994) Proc. Natl. Acad. Sci. U.S.A. 91, 6486-6490). We have now used antibodies raised against p145 which had been purified by Grb2 affinity chromatography and SDS-polyacrylamide gel electrophoresis to characterize this protein. p145 is neuron-specific and co distributes with dynamin in subcellular fractions of rat brain. Both proteins are partially recovered in soluble and particulate fractions. By immunofluorescence, p145 is closely co-localized with dynamin, which we show here to be highly concentrated in nerve terminals. In contrast to synapsin I, which is highly enriched in a purified synaptic vesicle fraction, both p145 and dynamin are de enriched in this fraction. However, both proteins are found on membranes which are immunoisolated with antibodies directed against the synaptic vesicle membrane protein synaptophysin, suggesting that dynamin and p145 are localized in part on organelles which represent intermediate stages in the reformation of synapatic vesicles during recycling. Finally, we have determined that p145, like dynamin, is a phosphoprotein which undergoes dephosphorylation in response to nerve terminal depolarization. These findings suggest that p145 participates with dynamin in synaptic vesicle endocytosis and recycling. PMID- 7982918 TI - The RNA polymerase I transcription factor, upstream binding factor, interacts directly with the TATA box-binding protein. AB - The accurate transcription of human rRNA genes by RNA polymerase I requires two transcription factors, upstream binding factor (UBF) and promoter selectivity factor (SL1). Human SL1 (hSL1) is a multisubunit complex, one of whose components is TATA box-binding protein (TBP). hSL1 binds to the core region of the rRNA promoter, but does so inefficiently in the absence of human UBF (hUBF). hUBF interacts with the upstream control element of the rRNA promoter and facilitates binding of hSL1. The molecular basis by which hUBF increases binding of hSL1 remains to be elucidated. In this report, we use an immobilized protein binding assay to identify and purify a 95-kDa TBP-binding polypeptide. Microsequence analysis reveals that the 95-kDa TBP-binding protein is hUBF. We show that hUBF is stably associated with TBP and is present in large TBP-containing complexes. Our results indicate that the cooperative binding of hUBF and hSL1 on the rRNA promoter is mediated by direct interaction between hUBF and TBP. We also provide evidence that hUBF associates with TFIID, a TBP-containing RNA polymerase II transcription factor. PMID- 7982919 TI - Osteonectin in matrix remodeling. A plasminogen-osteonectin-collagen complex. AB - Osteonectin is an adhesive glycoprotein synthesized constitutively by osteoblasts, endothelial cells, and megakaryocytes. Bone-derived and platelet derived osteonectins differ in their electrophoretic mobility and carbohydrate content, and each displays different affinities for collagen matrices. Both types of osteonectin bind to plasminogen (Kd(app), of 4.7 +/- 1.0 x 10(-8) M for bone osteonectin and 1.2 +/- 0.1 x 10(-7) M for platelet osteonectin). The osteonectin plasminogen interaction is inhibited by alpha 2-antiplasmin and epsilon aminocaproic acid, suggesting that the interaction is mediated through the kringle 1 region of plasminogen. Both osteonectins enhance the rate of plasmin generation by tissue-type plasminogen activator to approximately the same extent as fibrinogen. Equilibrium binding measurements conducted using total internal reflection fluorescence spectroscopy indicate that plasminogen binds to collagen in the presence of bone osteonectin (Kd = 1.30 +/- 0.1 x 10(-7) M). No binding of plasminogen to collagen matrix was detected in the presence of platelet osteonectin or in the absence of bone osteonectin. Bone osteonectin-dependent binding of plasminogen to collagen matrix is reversed by the addition of epsilon aminocaproic acid. The ability of both types of osteonectin to bind to and influence plasminogen activation and of bone osteonectin to anchor plasminogen on collagen matrices suggests that osteonectin may play a role in directing extracellular matrix proteolysis. PMID- 7982920 TI - Activation of the Eck receptor protein tyrosine kinase stimulates phosphatidylinositol 3-kinase activity. AB - The Eph/Eck subfamily of receptor protein tyrosine kinases is currently the largest subfamily of receptor protein tyrosine kinases with a dozen members (Van der Geer, P., Hunter, T., and Lindberg, R. A. (1994) Annu. Rev. Cell Biol. 10, 251-337). Using the cytoplasmic domain of Eck as bait in a yeast two-hybrid screen of mouse embryonic and T-cell cDNA libraries, it was discovered that the p85 subunit of phosphatidylinositol 3-kinase bound Eck. Further, using glutathione S-transferase fusion proteins, it was found that the C-terminal src homology 2 domain of the p85 subunit specifically interacted with Eck. Additionally, Eck coimmunoprecipitated with p85 in ligand activated cells confirming their interaction in vivo. In keeping with the above observations, activation of Eck by its ligand, B61, increased phosphatidylinositol 3-kinase activity. This is the first description of a signal transduction pathway initiated by any member of the Eph/Eck family. PMID- 7982921 TI - The catalytic cycle of the vacuolar H(+)-ATPase. Comparison of proton transport in kidney- and osteoclast-derived vesicles. AB - To characterize the catalytic cycle involved in the initial rate of proton transport by the vacuolar ATPases (V-ATPase), we have analyzed and compared the catalytic parameters of V-ATPase-dependent proton transport in vesicles from chicken kidney or purified osteoclasts. The relationship of acidification to ATP obeyed simple Michaelis-Menten kinetics with a single Km for ATP of 62 microM in the kidney and 191 microM in the osteoclast. The activity was dependent on the presence of Mg2+, with a single Km of 258 microM MgCl2 in the kidney and 504 microM MgCl2 in the osteoclast. In both preparations, ADP competed with ATP and inhibited the proton transport (Ki = 37 microM in kidney and 17 microM in osteoclast). Phosphate was found to be a noncompetitive inhibitor of ATP, with a calculated Ki of about 10.5 and 5.5 mM, respectively. In both preparations, the catalytic mechanism determining the V-ATPase-mediated proton transport, fits the model of a "uni-bi-ordered release" mechanism. According to this model, ATP is the single substrate, and P(i) and ADP are the two products where phosphate, being noncompetitive, is released first and ADP, being competitive, second. The findings of an elevated Km for ATP and Mg2+ and a decrease in the Ki of ADP and phosphate in the osteoclast relative to the kidney preparation suggests that the V-ATPases present in these two tissues may differ. PMID- 7982922 TI - Differential coupling of G protein alpha subunits to seven-helix receptors expressed in Xenopus oocytes. AB - Xenopus oocytes were used to examine the coupling of the serotonin 1c (5HT1c) and thyrotropin-releasing hormone (TRH) receptors to both endogenous and heterologously expressed G protein alpha subunits. Expression of either G protein coupled receptor resulted in agonist-induced, Ca(2+)-activated Cl- currents that were measured using a two-electrode voltage clamp. 5HT-induced Cl- currents were reduced 80% by incubating the injected oocytes with pertussis toxin (PTX) and inhibited 50-65% by injection of antisense oligonucleotides to the PTX-sensitive Go alpha subunit. TRH-induced Cl- currents were reduced only 20% by PTX treatment but were inhibited 60% by injection of antisense oligonucleotides to the PTX insensitive Gq alpha subunit. Injection of antisense oligonucleotides to a novel Xenopus phospholipase C-beta inhibited the 5HT1c (and Go)-induced Cl- current with little effect on the TRH (and Gq)-induced current. These results suggest that receptor-activated Go and Gq interact with different effectors, most likely different isoforms of phospholipase C-beta. Co-expression of each receptor with seven different mammalian G protein alpha subunit cRNAs (Goa, Gob, Gq, G11, Gs, Golf, and Gt) was also examined. Co-expression of either receptor with the first four of these G alpha subunits resulted in a maximum 4-6-fold increase in Cl- currents; the increase depended on the amount of G alpha subunit cRNA injected. This increase was blocked by PTX for G alpha oa and G alpha ob co-expression but not for G alpha q or G alpha 11 co-expression. Co-expression of either receptor with Gs, Golf, or Gt had no effect on Ca(2+)-activated Cl- currents; furthermore, co-expression with Gs or Golf also failed to reveal 5HT- or TRH-induced changes in adenylyl cyclase as assessed by activation of the cystic fibrosis transmembrane conductance regulator Cl- channel. These results indicate that in oocytes, the 5HT1c and TRH receptors do the following: 1) preferentially couple to PTX-sensitive (Go) and PTX-insensitive (Gq) G proteins and that these G proteins act on different effectors, 2) couple within the same cell type to several different heterologously expressed G protein alpha subunits to activate the oocyte's endogenous Cl- current, and 3) fail to couple to G protein alpha subunits that activate cAMP or phosphodiesterase. PMID- 7982923 TI - A low affinity chimeric human alpha/beta-granulocyte-macrophage colony stimulating factor receptor induces ligand-dependent proliferation in a murine cell line. AB - The high affinity receptor for granulocyte-macrophage colony-stimulating factor (GM-CSF) is composed of at least two subunits, an 85-kDa low affinity GM-CSF binding protein (alpha-GMR) and a 120-kDa beta-subunit (beta-GMR) necessary for high affinity binding and signal transduction. Previous studies have shown that deletion of the intracellular domain of alpha-GMR inactivates the receptor's ability to support proliferation, but has no effect on GM-CSF binding. Using anti alpha-GMR- and anti-beta-GMR-specific antibodies, we show that alpha-GMR and beta GMR coprecipitate only after GM-CSF binding, suggesting that binding of GM-CSF induces stabilization or assembly of an activated receptor complex involving recruitment of beta-GMR chains. To understand the contribution of each subunit of this receptor to the generation of an activated receptor complex, we attempted to construct minimal receptors with some or all of the functions of the wild-type heterodimer. We found that a hybrid human alpha/beta-GMR molecule in which the extracellular and transmembrane segments are composed of alpha-GMR sequences and the intracellular segment is composed of beta-GMR bound GM-CSF with low affinity, but activated tyrosine kinase activity, induced receptor internalization, and supported short- and long-term proliferation of transfected Ba/F3 cells. At least 1 ng/ml human GM-CSF was required for growth stimulation, and maximal proliferation occurred at a concentration of 10 ng/ml. This was 10-100-fold more than needed to stimulate growth of Ba/F3 cells expressing both full-length human alpha-GMR and beta-GMR and 1000-fold less than needed to stimulate growth of Ba/F3 cells expressing only human alpha-GMR. These results indicate that the cytoplasmic domain of alpha-GMR is not required to initiate a unique signaling event for proliferation in Ba/F3 cells, but can be functionally replaced by the cytoplasmic domain of beta-GMR. PMID- 7982924 TI - Structural characterization of an Ascaris myoglobin. AB - Globin was purified from the body wall of adults of the parasitic nematode Ascaris suum. Internal peptide fragments were sequenced and cDNAs encoding a polypeptide of 154 amino acids isolated by polymerase chain reaction. The polypeptide lacks a signal sequence, identifying it as a cytosolic myoglobin-like species. The native protein is a dimer. The predicted amino acid sequence shares several unusual substitutions with other nematode globins. Like the abundant pseudocoelomic A. suum hemoglobin it has a Tyr at B10 and a Gln at E7, substitutions thought to be determinants of high affinity. However, the 10-fold lower oxygen affinity of body wall globin suggests that in this molecule Tyr(B10) does not form an additional hydrogen bond with the heme bound oxygen. Evolutionary analysis of the nematode globins suggests that the monodomain myoglobin-like molecules and the two-domain hemoglobin-like molecules diverged about 500 million years ago, well before the divergence of the ascarid genera Ascaris and Pseudoterranova. The absence of introns in the A. suum myoglobin, in contrast to other nematode globin genes, is consistent with the hypothesis that during evolution intron elimination was the predominant event. PMID- 7982925 TI - Structural and kinetic studies of the 10 S<==>6 S transition in smooth muscle myosin. AB - The conformational transitions that smooth muscle myosin undergoes after nucleotide binding have been examined using fluorescently labeled nucleotides and regulatory light chain. The 10 S conformation of smooth muscle myosin could be induced by addition of 1-N6-ethenoadenosine or mant ADP plus beryllium fluoride, as well as by mant adenosine 5'-(beta,gamma-iminotriphosphate) (AMPPNP). Fluorescence lifetime studies using 1-N6-ethenoadenosine plus beryllium fluoride reveal two components for both (10 S)- and (6 S)-myosins, with little difference in the values of these lifetimes, their fractional amplitudes, or solute accessibilities. Anisotropy decay studies of myosin-mant nucleotide complexes demonstrate that the rotational correlation time for (10 S)-myosin is nearly 4 fold longer than that for (6 S)-myosin. Qualitatively similar results were obtained with a 5-[[[2(iodoacetyl)amino]ethyl]amino]naphthalene-1-sulfonic acid fluorescent probe attached to the regulatory light chain. Mant AMPPNP can be trapped in the active site by (10S)-myosin. Actin accelerates this release rate by 40-50-fold. These studies reveal: 1) reduction in nucleotide release rate by converting (6S) to (10S)-myosin is not due to a reduction in solute accessibility of the nucleotide 2) the heads in (10 S)-myosin are rigidly attached to the rest of the molecule, while in (6 S)-myosin, they have segmental flexibility, 3) regulatory light chain phosphorylation mimics the effect of high salt in enhancing segmental flexibility of the myosin heads, and 4) actin can induce the unfolding of (10 S)-myosin in the absence of regulatory light chain phosphorylation. PMID- 7982926 TI - Differential binding domains of peptide and non-peptide ligands in the cloned rat kappa opioid receptor. AB - This study was to identify specific regions in kappa opioid receptors that accounted for binding selectivity of kappa ligands. Six chimeric mu/kappa receptors were constructed from cloned rat kappa and mu opioid receptors and transiently expressed in COS-1 cells. All six chimeric mu/kappa receptors bound [3H] diprenorphine with high affinities, indicating that these chimeras retain opioid receptor conformation. Binding affinities of three peptide ligands (dynorphin A, alpha-neo-endorphin, and dynorphin B) and three nonpeptide ligands (norbinaltorphimine, U50,488H, and U69,593) for chimeras were determined and compared to those for mu and kappa opioid receptors. The second extracellular loop and the adjoining C-terminal portion of the fourth transmembrane helix were essential for the high affinity binding of dynorphin A, alpha-neo-endorphin, and dynorphin B to the kappa receptor. The third extracellular loop and the sixth and seventh transmembrane helices played an important role in determining the selectivity of nor-binaltorphimine for the kappa over the mu receptor. U50,488H and U69,593 appeared to require the whole kappa receptor except the second extracellular loop to attain high affinity binding. Thus, the kappa opioid receptor has differential binding domains for peptide and non-peptide ligands. PMID- 7982927 TI - Free metal ion-independent oxidative damage of collagen. Protection by ascorbic acid. AB - In this paper we demonstrate that in the absence of free metal ions, active oxygen species, generated by activated macrophages or xanthine/xanthine oxidase (XOD), carry out oxidative degradation of collagen fibrils type I in conjunction with proteases. The collagen degradation is completely prevented by ascorbate (AH2) but not by catalase. The free metal ion-independent collagen degradation is a two-step process: (i) oxidation of collagen and (ii) subsequent proteolytic cleavage of the oxidatively modified collagen. AH2 completely prevents collagen oxidation and thereby protects the collagen from subsequent proteolytic degradation. This is in contrast to free metal ion-catalyzed spontaneous fragmentation of collagen, which is accelerated by AH2 and inhibited by catalase (Kato, Y., Uchida, K., and Kawakishi, S. (1992) J. Biol. Chem. 267, 23646-23651). Studies using xanthine/XOD and model polypeptides, namely, poly-L-Pro, poly-L hydroxyproline, poly-L-Lys, and poly(Pro-Gly-Pro) indicate that although O2-. is needed along with XOD, oxidation of model polypeptides appears to be a direct function of XOD iron, which is also stimulated by cytochrome P450. PMID- 7982928 TI - Probing protein-protein interactions. The ribose-binding protein in bacterial transport and chemotaxis. AB - A number of mutations at Gly134 of the periplasmic ribose-binding protein of Escherichia coli were examined by a combined biochemical and structural approach. Different mutations gave rise to different patterns of effects on the chemotaxis and transport functions. The smallest residue (alanine) had the least effect on transport, whereas large hydrophobic residues had the smallest effect on chemotaxis. Comparison of the x-ray crystal structure of the G134R mutant protein (2.5-A resolution) to that of the wild type (1.6-A resolution) showed that the basic structure of the protein was unaltered. The loss of chemotaxis and transport functions in this and similar mutant proteins must therefore be caused by relatively simple surface effects, which include a change in local main chain conformation. The loss of chemotaxis and transport functions resulting from the introduction of an alanine residue at position 134 was suppressed by an additional isoleucine to threonine mutation at residue 132. An x-ray structure of the I132T/G134A double mutant protein (2.2-A resolution) showed that the changes in local structure were accompanied by a diffuse pattern of structural changes in the surrounding region, implying that the suppression derives from a combination of sources. PMID- 7982929 TI - Myristate exchange. A second glycosyl phosphatidylinositol myristoylation reaction in African trypanosomes. AB - The variant surface glycoprotein of African trypanosomes has a glycosyl phosphatidylinositol (GPI) anchor that is unusual in that its fatty acids are exclusively myristate. We showed previously that the myristate is added to a free GPI in a fatty acid remodeling reaction involving deacylation and reacylation, forming glycolipid A, the anchor precursor. We now demonstrate that trypanosomes have a second pathway for GPI anchor myristoylation distinct from the fatty acid remodeling pathway, which we call "myristate exchange." This reaction involves exchange of myristate into both the sn-1 and sn-2 positions of glycolipid A, which already contain myristate. Myristoyl-CoA, the probable myristate donor in the exchange reaction, has an apparent Km of about 6 nM. We have now identified a lyso-GPI, named theta', which has myristate as its sole fatty acid; the kinetics of formation and utilization of theta' are consistent with it being an intermediate in exchange. Myristate exchange and fatty acid remodeling appear to occur in different subcellular compartments, and the two reactions have different sensitivities to inhibitors. The myristate exchange reaction may be a proofreading system to ensure that the fatty acids on variant surface glycoproteins are exclusively myristate. PMID- 7982930 TI - Low temperature increases the abundance of early light-inducible transcript under light stress conditions. AB - Green pea plants respond to light stress by expression of a nuclear ELIP (early light-inducible protein) gene. Here we report that the accumulation of ELIP transcript in pea plants during light stress is enhanced by low temperature treatment. The enhanced level of ELIP transcript during combined light and cold stress was found to be due to an increased stability of ELIP messenger RNA under these conditions. This transcript is translatable in vitro. In vivo, however, the amount of accumulated protein in the thylakoids declines with the decrease in the temperature because the translational activity is strongly reduced already at 10 degrees C. Plants exposed to light stress at temperatures that do not allow accumulation of ELIP transcript respond by induction of ELIP mRNA and protein during recovery at low light intensity and ambient temperature. The amount of protein that accumulates as a result of this "memory effect" is, however, much lower than that which accumulates as a result of direct light stress. The memory of a perceived light stress persists in plants stored at low temperature for at least 3 h, and the stress response can be released after an increase in temperature. Prolonged cold treatment, however, has a negative effect on the translatability of the ELIP transcript that accumulates during recovery. PMID- 7982931 TI - Potent peptide inhibitors of stromelysin based on the prodomain region of matrix metalloproteinases. AB - Stromelysin is secreted as an inactive zymogen that is activated in the extracellular space by cleavage of the His81-Phe82 bond with the release of the 81-amino acid propeptide domain. This segment contains a 12-amino acid sequence (MRKPRC75GVPDVG) that is highly conserved in all matrix metalloproteinases. Previous studies have shown that the hexapeptide, Ac-RCGVPD-NH2, and the pentapeptide, Ac-RCGVP-NH2, based on this region retain significant inhibitory activity. This new structure-activity relationship study of both peptides has shown that only Cys75 and Val77 are essential for inhibitory activity. Peptides based on this series inhibited stromelysin and collagenase with equal potency. Additional peptides spanning this region were synthesized in order to focus on these two sites. Significantly, isocysteine was substituted for Cys75 without significant loss of inhibitory activity. Tyr-(2,6-dichlorobenzyl) was substituted for Val77. The introduction of these 2 new residues into Ac-CGVP-NH2 produced a very potent inhibitor, Ac-isoCGY-(2,6 dichlorobenzyl)-P-NH2 with an IC50 of 3 microM. The following factors, acting in combination, determine the inhibitory activity of peptides in this series: distance between the sulfur atom and the peptide backbone, coordination geometry of the thiol side chain with the active site zinc, and conformational flexibility of the side-chain. PMID- 7982932 TI - DNA binding specificity and function of retinoid X receptor alpha. AB - Retinoid X receptors are members of the erbA superfamily of ligand-inducible transcription factors. Similar to several other members of this gene family, retinoid X receptors are known to bind to the hexameric DNA sequence AGGTCA. After binding to a direct repeat of this hexamer with a one-base pair spacer, retinoid X receptor homodimers are able to activate transcription in the presence of the ligand 9-cis-retinoic acid. However, it is not known if AGGTCA represents the highest affinity binding site for retinoid X receptors. A combination of the electrophoretic mobility shift assay and polymerase chain reaction was used to isolate from a pool of random DNA those sequences that bind retinoid X receptors with highest affinity. This approach, combined with mutational analysis and DNA footprinting, led to the identification of the seven-base pair sequence GGGGTCA as the highest affinity retinoid X receptor binding site. A direct repeat of this sequence is substantially more active than a direct repeat of AGGTCA as a retinoid X response element. PMID- 7982933 TI - Engineering the S2 subsite specificity of human cathepsin S to a cathepsin L- and cathepsin B-like specificity. AB - The primary specificity of papain-like proteinases is largely determined by S2-P2 site interactions. According to the three-dimensional structure of a papain inhibitor complex, the S2 subsite is defined by residues 67, 68, 133, 157, 160, and 205, with residues 133, 157, and 205 integrated into the wall and bottom of the side chain binding cavity. The S2 binding site specificity of this enzyme has been altered to mimic that of cathepsin B or L by the application of site directed mutagenesis at these latter three positions in the cathepsin S sequence. The replacement of Gly-133 in cathepsin S by an alanine residue that is normally found at this position in both cathepsin B and L results in a pattern of specificity toward hydrophobic residues in P2 that is very similar to that of cathepsin B and L. The replacement of other cathepsin S S2 subsite residues with their cathepsin L equivalents (mutants Val-157-->Leu, Phe-205-->Ala) does not significantly change the specificity of cathepsin S. Cathepsin B is distinguished from both cathepsin L and S by its ability to efficiently hydrolyze substrates containing a basic P2 residue. A single mutation in position 205 of cathepsin S (Phe-205-->Glu) results in a change of specificity toward that of cathepsin B, i.e. the second-order rate constant for the hydrolysis of the cathepsin B specific substrate benzyloxycarbonyl-Arg-Arg-4-methyl-7-coumaryl-amide is increased 77-fold for this mutant compared with the wild-type enzyme. A cathepsin S double mutant Gly-133-->Ala/Phe-205-->Glu is characterized by somewhat improved kinetic parameters compared with the Phe-205-->Glu single mutant. The hydrolysis rate of the benzyloxy-carbonyl-Arg-Arg-4-methyl-7-coumarylamide substrate by this double mutant is 130-fold higher than that of the wild-type enzyme. As with cathepsin B, the activities of the Phe-205-->Glu single and the Gly-133- >Ala/Phen-205-->Glu double mutants of cathepsin S toward the dibasic substrate is modulated by an additional ionizable group with a pKa of 5.7. PMID- 7982934 TI - High affinity C10-Oeq ester derivatives of ryanodine. Activator-selective agonists of the sarcoplasmic reticulum calcium release channel. AB - The plant alkaloids ryanodine and dehydroryanodine are specific and potent modulators of the sarcoplasmic reticulum calcium release channel. In the present study, acidic, basic, and neutral side chains esters of these diterpene compounds were prepared and their pharmacologic activities were assessed. Binding affinities of the novel C10-Oeq ester derivatives for the sarcoplasmic reticulum Ca2+ release channel were evaluated with sarcoplasmic reticular vesicles prepared from rabbit skeletal muscle. Kd values of the derivatives varied 500-fold, ranging from 0.5 to 244 nM. In comparison, Kd values for ryanodine and dehydroryanodine were 4.4 nM and 5.4 nM, respectively. Basic substituents at the C10-Oeq side chain terminus produced the highest affinity derivatives (Kd values from 0.5 to 1.3 nM). Neutral and/or hydrophobic side chain derivatives exhibited intermediate affinities for the high affinity ryanodine receptor site (Kd values from 2.5 to 39 nM), whereas a derivative with a terminal acidic group had the lowest affinity (Kd value > 100 nM). Certain of the higher affinity C10-Oeq derivatives were evaluated more extensively for their pharmacologic activity on the sarcoplasmic reticular Ca2+ release channel. Both channel activating (opening) and deactivating (closing) actions were assessed from the ability of the ryanoids to alter Ca2+ efflux rates from skeletal junctional sarcoplasmic reticular vesicles that had been passively loaded with Ca2+. The natural Ryania secondary metabolites ryanodine, dehydroryanodine and esters E and F, all exhibit antithetical concentration-effect curves, indicating both activator and deactivator actions. In contrast, the semi-synthetic C10-Oeq esters selectively activate the Ca2+ release channel. Half-maximal concentrations for such activation (EC50 act) ranged from 0.87 microM to 4.2 microM, compared with an EC50 act of 1.3 microM for ryanodine. These derivatives were also evaluated for their ability to augment ATP-dependent CA2+ accumulation by cardiac junctional sarcoplasmic reticular vesicles, an effect that results from deactivation of the Ca2+ release channels. None of the derivatives tested was able to significantly augment Ca2+ accumulation, further substantiating their inability to deactivate the sarcoplasmic reticular Ca2+ release channel. Additionally, these derivatives functionally antagonized the action of ryanodine to close the Ca2+ release channel. The results presented demonstrate that these C10-Oeq ester derivatives of ryanodine and dehydroryanodine bind specifically to the SR Ca2+ release channel, selectively activate the channel, and, although they fail to effect channel closure, they nevertheless functionally compete with ryanodine at its low affinity (deactivator) site(s). PMID- 7982935 TI - Alpha 2-adrenergic stimulation promotes preadipocyte proliferation. Involvement of mitogen-activated protein kinases. AB - Primary cultures of rat preadipocytes were shown to express alpha 2- and beta adrenoreceptors when maintained in serum-deprived medium. alpha 2-Adrenoreceptor stimulation led to an increase in cell number, whereas beta-adrenoreceptor stimulation was without effect. On 3T3-F442A clones stably transfected with the human alpha 2-C10 gene and expressing a physiologically related number of alpha 2 adrenoreceptors to overexpression, the proliferative effect of alpha 2 adrenoreceptor agonist UK14304 was proportional to the level of alpha 2 adrenoreceptor expressed in individual clones and required alpha-2 adrenoreceptor stimulation. Analysis of the signaling pathway linked to alpha 2-adrenoreceptor activation showed that the mitogenic effect was adenylyl cyclase- and protein kinase C-independent. It was pertussis toxin-sensitive, implying the involvement of pertussis toxin-sensitive G proteins. The activation of the mitogen-activated protein kinase pathway was increased after alpha 2-adrenoreceptor stimulation in both 3T3-F442 clones and rat preadipocytes and inhibited by pertussis toxin treatment. So, catecholamines are involved in the control of white preadipocyte proliferation through the alpha 2-adrenoreceptor activation, linked to the mitogen-activated protein kinase pathway. PMID- 7982936 TI - Enzymatic synthesis and characterizations of cyclic GDP-ribose. A procedure for distinguishing enzymes with ADP-ribosyl cyclase activity. AB - Cyclic nucleotides such as cAMP and cGMP are second messengers subserving various signaling pathways. Cyclic ADP-ribose (cADPR), a recently discovered member of the family, is derived from NAD+ and is a mediator of Ca2+ mobilization in various cellular systems. The synthesis and degradation of cADPR are, respectively, catalyzed by ADP-ribosyl cyclase and cADPR hydrolase. CD38, a differentiation antigen of B lymphocytes, has recently been shown to be a bifunctional enzyme catalyzing both the formation and hydrolysis of cADPR. The overall reaction catalyzed by CD38 is the formation of ADP-ribose and nicotinamide from NAD+, identical to that catalyzed by NADase. The difficulties in detecting the formation of cADPR have led to frequent identification of CD38 as a classical NADase. In this study, we show that both ADP-ribosyl cyclase and CD38, but not NADase, can cyclize nicotinamide guanine dinucleotide (NGD+) producing a new nucleotide. Analyses by high performance liquid chromatography and mass spectroscopy indicate the product is cyclic GDP-ribose (cGDPR) with a structure similar to cADPR except with guanine replacing adenine. Compared to cADPR, cGDPR is a more stable compound showing 2.8 times more resistance to heat induced hydrolysis. These results are consistent with a catalytic scheme for CD38 where the cyclization of the substrate precedes the hydrolytic reaction. Spectroscopic analyses show that cGDPR is fluorescent and has an absorption spectrum different from both NGD+ and GDPR, providing a very convenient way for monitoring its enzymatic formation. The use of NGD+ as substrate for assaying the cyclization reaction was found to be applicable to pure enzymes as well as crude tissue extracts making it a useful diagnostic tool for distinguishing CD38-like enzymes from degradative NADases. PMID- 7982937 TI - Two murine GSTpi genes are arranged in tandem and are differentially expressed. AB - An 8-kilobase mouse genomic fragment containing two intact glutathione S transferase (GST) genes has been isolated from a mouse lambda genomic library. Each of the genes (designated mGSTpiA and mGSTpiB) is less than 3 kilobases in size and is comprised of seven exons that give rise to a 630-base pair open reading frame encoding 209 amino acids. The deduced amino acid sequences of the gene products differ in only 6 amino acids at positions 10, 11, 89, 104, 106, and 109. These two genes are highly homologous to rat GST-P and to a lesser extent to human GST-pi. Northern blot analysis of mRNAs from a variety of mouse tissues demonstrated that mGSTpiB is ubiquitously expressed, whereas mGST-piA is more selectively expressed in gallbladder, colon, heart, and skeletal muscle. Primer extension analysis revealed four potential transcription start sites in mGST-piB and one in mGSTpiA. Although both genes were expressed in vitro and in vivo only mGSTpiB product metabolized 1-chloro-2,4-dinitrobenzene, a common GST substrate. Further in vitro expression studies of three chimeric mGSTpi genes suggested that one or both of the amino acids at positions 10 and 11 of mouse GSTpi enzymes are important for the enzyme's ability to metabolize 1-chloro-2,4-dinitrobenzene. PMID- 7982938 TI - Inhibition of degranulation of polymorphonuclear leukocytes by angiogenin and its tryptic fragment. AB - A degranulation inhibiting protein was purified to apparent homogeneity from plasma ultrafiltrates of patients with uremia using gel-permeation chromatography, ion-exchange chromatography, affinity chromatography on blue Sepharose, and ion-exchange chromatography on a Mono S HR 5/5 fast protein liquid chromatography column. The identity of the isolated degranulation inhibiting protein with angiogenin was demonstrated by amino acid sequence determination, immunoblotting, and identical inhibitory activity effects on leukocyte degranulation. At concentrations in the nanomolar range, the protein inhibited spontaneous degranulation of polymorphonuclear leukocytes (PMNL) to 40%. The protein discharge of cells, which were preincubated with nanomolar concentrations of angiogenin and then stimulated with the chemotactic peptide formyl-norleucyl leucyl-phenylalanyl-norleucyl-tyrosyl-leucine (FNLPNTL), was inhibited by 70%. Cellular functions such as chemotaxis, phagocytosis, and the oxidative respiratory burst were not obviously affected by angiogenin. A polyclonal antibody to human recombinant angiogenin abolished the inhibitory effect of the isolated protein upon PMNL. The same but reduced effect was induced by the disulfide C39-C92 containing tryptic angiogenin fragment L-H-G-G-S-P-W-P-P-C92-Q Y-R-G-L-T-S-P-C39-K, indicating a new, so far unknown biologically active site of angiogenin which is different from the sites responsible for angiogenic or ribonucleolytic activity. Two synthetic peptides containing residues 83-95, one with S92 instead of C92, revealed the same inhibitory effect on the protein degranulation of PMNL as the entire tryptic fragment. PMID- 7982939 TI - Long chain acyl coenzyme A and signaling in neutrophils. An inhibitor of acyl coenzyme A synthetase, triacsin C, inhibits superoxide anion generation and degranulation by human neutrophils. AB - Ligand-initiated activation of neutrophils triggers O2- generation, degranulation, phospholipid remodeling, and release of fatty acids such as arachidonate, oleate, and palmitate. Long chain acyl-CoA synthetase converts free fatty acids to acyl-CoA esters; a role for acyl-CoA esters as positive modulators of neutrophil functions is proposed. Physiologically relevant concentrations (1 10 microM) of acyl-CoA esters such as palmitoyl-CoA, enhanced O2- generation triggered by fMet-Leu-Phe or guanosine 5'-O-(thiotriphosphate) (GTP gamma S) but did not act as a trigger per se. Triacsin C, an inhibitor of acyl-CoA synthetase, inhibited fMet-Leu-Phe-elicited O2- generation and degranulation in a concentration-dependent manner. Triacsin C inhibited O2- generation elicited by fMet-Leu-Phe and GTP gamma S in electroporated neutrophils, indicating that acyl CoA acted downstream from the receptor. Palmitoyl-CoA reversed the Triacsin C induced inhibition of O2- generation. fMet-Leu-Phe elicited a prompt increase in total long chain acyl-CoA esters. Arachidonoyl-CoA and oleoyl-CoA were elevated 5 s after addition of fMet-Leu-Phe, while palmitoyl-CoA was not elevated until 60 s. Triacsin C inhibited fMet-Leu-Phe-initiated increases in arachidonoyl-CoA, oleoyl-CoA, and palmitoyl-CoA. These results suggest a role for acyl-CoA esters in regulating activation of O2- generation and degranulation at the G protein or subsequent step(s). PMID- 7982940 TI - Direct peptide profiling by mass spectrometry of single identified neurons reveals complex neuropeptide-processing pattern. AB - A novel strategy combining peptide fingerprinting of single neurons by matrix assisted laser desorption ionization mass spectrometry, molecular cloning, peptide chemistry, and electrospray ionization mass spectrometry was used to study the intricate processing pattern of a preprohormone expressed in identified neurons, the neuroendocrine light yellow cells (LYCs) of the gastropod mollusc, Lymnaea stagnalis. The cDNA encoding the precursor, named prepro-LYCP (LYCPs, light yellow cell peptides), predicts a straightforward processing into three peptides, LYCP I, II, and III, at conventional dibasic processing sites flanking the peptide domains on the precursor. However, matrix-assisted laser desorption ionization mass spectrometry of single LYCs revealed trimmed variant peptides derived from LYCP I and II. The variants were much more abundant than the intact peptides, indicating that LYCP I and II serve as intermediates in a peptide processing sequence. Using the molecular masses of the peptides as markers to guide their isolation by well established purification methods, the structural identities of the peptides could be confirmed by amino acid sequencing. Furthermore, matrix-assisted laser desorption ionization mass spectrometry could detect colocalization of a novel peptide with the LYCPs. PMID- 7982941 TI - Chimeric D1/D2 dopamine receptors. Distinct determinants of selective efficacy, potency, and signal transduction. AB - D1/D2 chimeras were constructed that had D1 dopamine receptor sequence at the amino-terminal end and D2 dopamine receptor sequence at the carboxyl-terminal end. The chimeras with the first four, five and six transmembrane domains of the D1 receptor (CH2, CH3, CH4, respectively) bound the D1 receptor antagonist [3H]SCH 23390 with high affinity. Reciprocal chimeras constructed with D2 receptor sequence at the amino-terminal end displayed no detectable specific binding of [3H]SCH 23390, [125I]epidepride, or [3H]spiperone. CH2, CH3, and CH4 had lower affinity than either D1 or D2 dopamine receptors for the nonselective antagonists and agonists and D2-selective antagonists tested. The chimeric receptors had affinities for three D1-selective ligands and the D2-selective agonist, quinpirole, that were intermediate between D1 and D2 receptor affinities for the drugs. The substantial loss or gain of affinity for three ligands upon replacement of D1 transmembrane VII with D2 sequence (CH4) suggests an important role for this region in the selectivity of these drugs. Stimulation of adenylyl cyclase activity by D1 agonists occurred in cells expressing CH3 and CH4, both of which included the D1 third cytoplasmic loop, but not in cells expressing CH1 or CH2, both with the D2 third cytoplasmic loop. However, only CH3 was able to mediate stimulation of adenylyl cyclase by quinpirole, implying that D2 receptor transmembrane domain VI was an important determinant of the selective efficacy of quinpirole. On the other hand, transmembrane domain VII was particularly important for the selective potency of quinpirole. Inhibition of beta-adrenergic receptor-stimulated adenylyl cyclase activity by dopamine was seen in cells expressing D2 receptors and CH1, but not CH2, CH3, or CH4. Thus, the third cytoplasmic loop of D1 dopamine receptors was crucial for the coupling of the receptors to Gs, but inhibition of adenylyl cyclase via Gi required structural features, such as the second cytoplasmic loop of the D2 receptor, in addition to the 3rd cytoplasmic loop. PMID- 7982942 TI - A mutant renin gene in familial elevation of prorenin. AB - A case of familial elevation of plasma prorenin levels was discovered during an epidemiological survey of a Dutch population. Trypsin-activated prorenin was elevated in the 58-year-old father, his son, and one of his sisters. All family members were normotensive and had normal plasma renin activities. Exon sequencing of the renin gene of the proband and of his son after polymerase chain reaction amplification identified a point mutation in the last exon of the gene (exon 10). A cytosine to thymine transition creates a premature stop codon at position 387 resulting in a truncated form of renin with 20 amino acids deleted from the carboxyl terminus. All family members presenting high levels of plasma prorenin were heterozygous for the mutation. Expression vectors carrying normal or mutated renin cDNA were transiently transfected into AtT-20 cells to test in vitro the functional consequences of this mutation. Measurements of renin activity and pulse-chase experiments indicated that the truncated renin is inactive and not secreted from transfected cells. We hypothesize that the abnormal gene product of the mutated allele alters renin sorting and propose that plasma prorenin elevation may result from a compensatory mechanism. PMID- 7982943 TI - Affinity labeling of aryl sulfotransferase IV. Identification of a peptide sequence at the binding site for 3'-phosphoadenosine-5'-phosphosulfate. AB - 2'-O-[(R)-Formyl(adenin-9-yl)-methyl]-(S)-glyceraldehyde 3'-triphosphate (also designated as ATP dialdehyde or ATPDA) was utilized as an affinity label for the 3'-phosphoadenosine 5'-phosphosulfate (PAPS) binding site of an aryl sulfotransferase. The sulfotransferase employed in these studies was rat hepatic aryl sulfotransferase (AST) IV (also known as tyrosine-ester sulfotransferase, EC 2.8.2.9), for which a cDNA had been previously cloned and expressed in Escherichia coli and the resulting enzyme purified to homogeneity. ATPDA was a time-dependent irreversible inhibitor of the recombinant AST IV, and this inhibition was prevented by including either PAPS or adenosine 3',5'-diphosphate (PAP) in the incubation of AST IV with ATPDA. Experiments relating covalent binding of [2,8-3H]ATPDA with catalytic activity indicated that 1 nmol of the affinity label was bound per nmol of AST IV subunit. Incubation of [2,8-3H]ATPDA with the enzyme followed by reduction with sodium cyanoborohydride, proteolysis with trypsin, and separation of the resulting peptides by high pressure liquid chromatography yielded two labeled peptide fractions. Automated sequence analysis showed that both modified peptide fractions were derived from the same sequence in AST IV: 63-Leu-Glu-Lys-Cys-Gly-Arg-68. Both the sequencing results and examination of the two peptide fractions by matrix-assisted laser desorption ionization mass spectrometry indicated that the ATPDA affinity label was bound to the hexapeptide at both lysine 65 and cysteine 66. These affinity labeled amino acids are located within a region of sequence in AST IV that shows considerable homology with various sulfotransferases that possess diverse specificities for acceptor substrates, and this may provide insight into PAPS binding in other sulfotransferases. PMID- 7982945 TI - Construction of a ferroxidase center in human ferritin L-chain. AB - Ferritins are 24-mer proteins which store and detoxify intracellular iron. Mammalian ferritins are made of two subunit types, the H- and L-chains, with different functional specificity. The H-chain has a metal-binding site (the ferroxidase center) which confers ferroxidase activity to the protein and accelerates iron incorporation. In the L-chain the center is substituted by a salt bridge. We performed several site-directed mutageneses in the L-chain with the aim to construct the center and confer ferroxidase activity to the protein. Most variants were insoluble and did not refold into homopolymers, probably due to electrostatic repulsion introduced by the substitutions. However, they formed hybrids when they were renatured together with the L- or H-chains. The heteropolymers made of 90% L-chain and 10% of an L-variant with all the ligand residues of the H-chain center had 25-30% of the ferroxidase activity of the H chain homopolymer. This corresponds to the activity of an H/L heteropolymer with 7% H-chain. It is concluded that: (i) it is possible to construct a ferroxidase center in the L-chain with an activity equivalent to that of the H-chain, (ii) the residues of the center interfere with the folding/assembly of the L-, but not of the H-chain, (iii) heteropolymers can be made even between ferritin subunits with large differences of refolding rates. PMID- 7982944 TI - Decreased binding of apolipoprotein (a) to familial defective apolipoprotein B 100 (Arg3500-->Gln). A study of the assembly of recombinant apolipoprotein (a) with mutant low density lipoproteins. AB - In familial defective apolipoprotein B-100 (FDB), glutamine is substituted for arginine at position 3500 of the amino acid sequence. This mutation alters the structure of low density lipoproteins (LDL) and reduces their binding to LDL receptors. We studied the assembly in vitro of FDB-LDL with two recombinant apo(a) (r-apo(a)) isoforms containing 17 or 18 kringle IV-type repeats, respectively. R-apo(a) complexed to LDL in a concentration- and time-dependent manner. When we mixed normal LDL at protein concentrations from 1 to 10 mg/liter with 200 micrograms/liter r-apo(a) and incubated for 20 h, 15-44% of r-apo(a) were bound to LDL, forming an artificial Lp(a)-like particle. With LDL from a homozygous FDB patient, only 2-16% of r-apo(a) were complexed; heterozygous FDB LDL bound 2-30% of r-apo(a). We also studied the effect of r-apo(a) on the interaction of the monoclonal antibody MB47 with normal and mutant apoB-100. FDB LDL displayed enhanced binding of MB47. Adducts generated from normal LDL and r apo(a) had an increased affinity for MB47, when compared to LDL alone. In contrast, r-apo(a) did not change MB47 reactivity when incubated with FDB-LDL. Altogether, our findings suggest that domains in apolipoprotein B which are important for the interaction with the LDL receptor play a role in the assembly of Lp(a) as well. They provide, in addition, an explanation for the observation that in Lp(a) of heterozygous FDB patients, the ratio of defective to normal apoB 100 is significantly smaller than in LDL from the same patients. PMID- 7982946 TI - In situ assay of light-stimulated G protein activity in Drosophila photoreceptor G protein beta mutants. AB - An in situ 35S-labeled guanosine 5'-3-O-(thio)triphosphate (GTP gamma S) binding procedure was developed to assay light-stimulated G protein activity in Drosophila compound eyes. We found that Drosophila with mutations in G beta e, an abundant photoreceptor-specific G protein beta subunit essential for photoexcitation, are defective in light-stimulated [35S]GTP gamma S binding. We confirmed that G beta e interacts with a GTP-binding protein by demonstrating that immunoprecipitation of G beta e is sensitive to GTP gamma S. These results suggest that G beta e functions as the beta subunit of a heterotrimeric G protein that couples photoactivation of rhodopsin to downstream components in the Drosophila phototransduction cascade. PMID- 7982947 TI - The structure of lipooligosaccharide produced by Neisseria gonorrhoeae, strain 15253, isolated from a patient with disseminated infection. Evidence for a new glycosylation pathway of the gonococcal lipooligosaccharide. AB - We studied the structure of the lipooligosaccharide (LOS) that is produced by Neisseria gonorrhoeae, strain 15253. This strain, recovered from a patient with disseminated infection, produces predominantly a single LOS component, and its oligosaccharide (OS) structure is different from those of previously studied LOSs. Definition of this OS structure provides additional information on the LOS biosynthesis. We determined that the 15253 OS has an unusual structure: 2 lactosyl residues at its nonreducing ends shown below, [formula: see text] where KDO is 2-keto-3-deoxy-mannooctulosonic acid and Hep is heptose. Comparison of this OS structure with those determined previously indicates the presence of a new glycosylation pathway for gonococcal OS biosynthesis: elongation of a GlcNAc linked heptose, in contrast to elongation of the other heptose by sequential addition of glycoses which results in the antigenic similarity with human glycolipids. The current study provides not only additional structural information on LOS expressed during different clinical states of infection but also evidence for the diversity of gonococcal LOS biosynthesis. This evidence may be helpful in understanding the pathogenesis involving gonococcal LOS. PMID- 7982948 TI - Substitution of serine for glycine 883 in the triple helix of the pro alpha 1 (I) chain of type I procollagen produces osteogenesis imperfecta type IV and introduces a structural change in the triple helix that does not alter cleavage of the molecule by procollagen N-proteinase. AB - Type I procollagen secreted by dermal fibroblasts from an individual with osteogenesis imperfecta type IV was a mixture of normal molecules and molecules that were post-translationally overmodified. The individual was heterozygous for a G to A transition in the COL1A1 gene that resulted in the substitution of serine for glycine 883 in one or both of the pro alpha 1 (I) chains. The thermal stability of molecules containing overmodified chains was lower by 2 degrees C than that of normal molecules. However, following cleavage of the molecules with vertebrate collagenase, the temperature of denaturation of the overmodified A fragments (residues 1-775 of the helix did not contain the substitution) was 2 degrees C greater than that of A fragments from normal molecules. The rates of cleavage by procollogen N-proteinase (EC 3.4.214.14) (N-proteinase) of procollagen molecules in normal and osteogenesis imperfecta samples were not significantly different. The procollagen molecules in the osteogenesis imperfecta sample were also indistinguishable from those in control samples by rotary shadowing electron microscopy. The results suggest that this substitution of serine for glycine in the alpha 1 (I) chain of procollagen, like the substitution of aspartate for the same glycine previously described (Lightfoot, S. J., Holmes, D. F., Brass, A., Grant, M. E., Byers, P. H., and Kadler, K. E. (1992) J. Biol. Chem. 267, 25521-25528), can alter the structure of the triple helix N-terminal to the site of the substitution. However, in contrast to the aspartate for glycine substitution, the structural change is insufficient to delay the cleavage of the procollagen by N-proteinase and results in a mild rather than lethal phenotype. PMID- 7982949 TI - Characterization of interactions between transducin alpha/beta gamma-subunits and lipid membranes. AB - The gamma-subunits of heterotrimeric guanine nucleotide-binding regulatory proteins (G-proteins) are isoprenylated and alpha-carboxyl methylated at their COOH-terminal cysteine residues. These modifications are necessary for membrane attachment of the beta gamma complex, but a requirement of an additional factor has been proposed for the stable binding. We explored a possible contribution of the blocked amino terminus of beta-subunits of bovine photoreceptor G-protein, transducin (T alpha/T beta gamma = Gt alpha/beta 1 gamma 1), and of three beta gamma complexes (beta 1 gamma 2, beta 1 gamma 3, and beta 1 gamma 7) purified from bovine brains. Structural analyses revealed that every beta 1-subunit has an N-acetylated serine, which is unlikely to contribute to the membrane association. Since neither protease nor heat treatment of photoreceptor membranes affected the membrane binding of T beta gamma, it seems unlikely that rhodopsin (or other membrane proteins) serves as an anchor protein for accepting T beta gamma. In fact, T beta gamma bound to phospholipid large unilamellar vesicles (LUVs), of which the polar head groups strongly influenced the binding: T beta gamma alone showed 2-fold higher binding for negatively charged phosphatidylserine-LUVs than for neutral phosphatidylcholine (PC)-LUVs, while the affinity of T alpha/T beta gamma complex for the phosphatidylserine-LUVs was lower than that for the PC LUVs. These results indicate that 1) an ionic interaction between T beta gamma and membrane surface plays an important role in the stable membrane association, and 2) the domain(s) of T beta gamma responsible for the association would be different between trimeric and dissociated states. We also found that synthetic peptides corresponding to the COOH-terminal region of T gamma inhibited T alpha-T beta gamma interaction only when the peptides were isoprenylated. This suggests that the isoprenyl moiety is located at the contact site between the subunits, not at the membrane-binding domain, when T beta gamma is complexed with T alpha. PMID- 7982950 TI - A mechanism of proton translocation by F1F0 ATP synthases suggested by double mutants of the a subunit. AB - Three amino acid residues in the a subunit of the Escherichia coli F1F0 ATP synthase are essential for proton translocation: Arg210, Glu219, and His245. In this study, the essential glutamic acid has been relocated to position 252 with retention of function. It had been known that Gln252 can be replaced by Glu without significant effect. To test whether Q252E would function in the absence of Glu219, a "site-directed second-site suppressor" experiment was designed. Saturation mutagenesis was applied to residue Glu219, and 14 different amino acid substitutions were isolated, five of which permitted growth on succinate minimal medium at 37 degrees C: Asp, Lys, Gly, Ala, and Ser. These results indicate that Q252E can provide the essential carboxyl group normally provided by Glu219, but that strict requirements are placed on the residue at position 219. We interpret these results to mean that the Q252E must occupy, at least partially, the normal position of Glu219. We present a novel mechanism of proton translocation by F1F0 ATP synthases that includes a rotating oligomer of c subunits, in which the Asp61 of two c subunits simultaneously interact with Glu219 and Arg210 of the a subunit. This mechanism can be adapted for both mitochondrial and sodium-driven bacterial ATP synthases. PMID- 7982951 TI - Identification of in vivo brain-derived neurotrophic factor-stimulated autophosphorylation sites on the TrkB receptor tyrosine kinase by site-directed mutagenesis. AB - Brain-derived neurotrophic factor (BDNF) interacts with the TrkB receptor tyrosine kinase, the tyrosine kinase domain of which has homology with the insulin receptor subfamily of protein kinases. This includes the conservation of three regulatory tyrosines (residues 670, 674, and 675) known to play a crucial role in signal transmission by the insulin receptor (tyrosines 1158, 1162, and 1163). Wild-type TrkB and TrkB mutants with Y670F, Y674F/Y675F, Y751F (the tyrosine reported to be important in phosphatidylinositol 3-kinase binding (Obermeier, A., Lammers, R., Wiesmuller, K. H., June, G., Schlessinger, J., and Ullrich, A. (1993) J. Biol. Chem. 268, 22963-22966)), and K540R (consensus ATP binding lysine) substitutions were transiently expressed in COS cells for analysis of phosphorylation sites by two-dimensional phosphopeptide mapping. TrkB phosphorylation sites were also studied in MG86 cells stably expressing wild-type TrkB. In addition, the mutants were expressed in Chinese hamster ovary cells for analysis of the ability of the receptor to mediate BDNF-stimulated transcription from a 12-O-tetradecanoylphorbol-13-acetate response element (TRE). BDNF stimulated the phosphorylation of wild-type TrkB on multiple tyrosine and serine residues. This phosphorylation occurred on tyrosines 670, 674, and 675 plus two other tyrosines and at least two serines that were not unequivocally identified. Wild-type TrkB mediated a pronounced stimulation of TRE-dependent transcription. A Y674F/Y675F, but not Y670F, substitution dramatically inhibited this response. Surprisingly, in COS cells, a Y751F substitution induced dramatically lower tyrosine and serine phosphorylation at all sites but mediated a normal BDNF stimulated activation of a TRE. Our results demonstrate a critical role for the phosphorylation of tyrosines 674 and 675 in BDNF-dependent signaling by wild-type TrkB. PMID- 7982952 TI - Assembly of synthetic laminin peptides into a triple-stranded coiled-coil structure. AB - Laminin, a large multidomain glycoprotein specific to basement membranes, is a heterotrimer with alpha, beta, and gamma chains held together in an alpha-helical coiled-coil structure. Synthetic peptides comprising two 51-mers (B1 and B2) from the beta 1 and gamma 1 subunits and a 55-mer (M) from alpha 2 were used to study the molecular mechanisms in laminin chain assembly. Using the synthetic peptides in various mixing experiments, the heterotrimer (B1-B2-M) was preferentially produced. The thermal stability of the heterotrimer increased dramatically (by approximately 20 degrees C) over that of the B1-B2 heterodimer as measured by circular dichroism (CD) spectroscopy. The B1-B1 homodimer (Tm = 60 degrees C) showed higher thermal stability when compared to B1-B2 and B2-B2 dimers. However, the B1 + B2 mixture produced principally the B1-B2 heterodimer. These results suggested that the preferential formations of heterodimer was regulated by kinetic interactions between each chain. The B2 and M peptides have many hydrophobic isoleucine residues which were replaced by leucines. These substitutions were predicted to favor an alpha-helical conformation and a higher propensity for zipper formation. B2L and ML, in which all isoleucine residues were replaced by leucine, showed significantly increased alpha-helicities. While B2L was able to form heterodimers and heterotrimers similar to B2, ML was not able to participate in heterotrimer formation as efficiently as the M peptide. The thermal stability of B1-B2L was comparable to that of B1-B2, but B2L and/or ML containing trimers showed lower thermal stability than B1-B2-M. These results suggest that the isoleucine residues in the alpha 2 and gamma 1 chains are critical for stabilizing the heteromeric triple-stranded coiled-coil structure. PMID- 7982953 TI - Carbohydrate binding specificity of the B-cell maturation mitogen from Artocarpus integrifolia seeds. AB - Artocarpin, a mannose-specific lectin, is a homotetrameric protein (M(r) 65,000) devoid of covalently attached carbohydrates and consists of four isolectins with pI in the range 5-6.5. Investigations of its carbohydrate binding specificity reveal that among monosaccharides, mannose is preferred over glucose. Among mannooligosaccharides, mannotriose (Man alpha 1-3[Man alpha 1-6]Man) and mannopentaose are the strongest ligands followed by Man alpha 1-3Man. Extension of these ligands by GlcNAc at the reducing ends of mannooligosaccharides tested remarkably improves their inhibitory potencies, while substitution of both the alpha 1-3 and alpha 1-6 mannosyl residues of mannotriose and the core pentasaccharide of N-linked glycans (Man alpha 1-3[Man alpha 1-6]Man beta 1 4GlcNAc beta 1-4GlcNAc) by GlcNAc or N-acetyllactosamine in beta 1-2 linkage diminishes their inhibitory potencies. Sialylated oligosaccharides are non inhibitory. Moreover, the substitution of either alpha 1-3 or alpha 1-6 linked mannosyl residues of M5Gn or both by mannose in alpha 1-2 linkage leads to a considerable reduction of their inhibitory power. Addition of a xylose residue in beta 1-2 linkage to the core pentasaccharide improves the inhibitory activity. Considering the fact that artocarpin has the strongest affinity for the xylose containing hepasaccharide from horseradish peroxidase, which differs significantly from all the mannose/glucose-specific lectins, it should prove a useful tool for the isolation and characterization of glycoproteins displaying such structure. PMID- 7982954 TI - Characterization of the myosin-binding subunit of smooth muscle myosin phosphatase. AB - A myosin phosphatase was purified from chicken gizzard smooth muscle. The holoenzyme is a trimer and consists of 130,000-, 38,000-, and 20,000-Da subunits (in agreement with the results of Alessi et al.: Alessi, D., MacDougall, L. K., Sola, M. M., Ikebe, M., and Cohen, P. (1992) Eur. J. Biochem. 210, 1023-1035). The catalytic subunit, 38,000 Da, is the type 1 delta isoform, and its derived amino acid sequence is identical to the rat isoform. The larger subunit bound to myosin and also interacted with the catalytic subunit. cDNA clones encoding the large subunit were isolated from chicken gizzard cDNA libraries. Overlapping clones indicated the presence of two isoforms, and open reading frames of 2889 and 3012 bases were obtained. These encoded proteins of 963 and 1004 amino acids, with masses of 106,700 and 111,600 Da, respectively. The insert in the larger isoform is in the center of the molecule, at residues 512-552. The N-terminal third of the molecule is composed of eight repeat sequences, similar to the cdc10/SWI6 or ankyrin repeat. Myosin binding and binding to the catalytic subunit are properties of a 58,000-Da fragment that represents the N-terminal part of the molecule. PMID- 7982955 TI - The stress response to loss of signal recognition particle function in Saccharomyces cerevisiae. AB - It has been shown previously that growth and endoplasmic reticulum (ER) translocation defects occur in response to depletion of the 54-kDa subunit of signal recognition particle (SRP54) in Saccharomyces cerevisiae (Hann, B. B., and Walter, P. (1991) Cell 67, 131-144). We report here that cells depleted of SRP54p undergo a general stress response, the onset of which is observed almost two-cell doublings after SRP54 protein levels fall below the limits of detection. The stress response to SRP54p depletion occurs in two distinct phases, unlike the response to other stressors such as heat shock. In the initial phase, the cytoplasmic Hsp70 levels are drastically increased coincident with an abrupt slowing of growth and accumulation of untranslocated species of the ER-resident chaperone BiP. During this first response, levels of the yeast DnaJ homolog Ydj1p are also increased. In the second phase, which is detected 5 h later, levels of the cytoplasmic heat shock proteins Hsp82 and Hsp104 are increased. BiP is also induced during this second phase, while the ER levels of the resident foldase protein disulfide isomerase are significantly reduced. Since only those cytoplasmic stress proteins which have been shown to participate in membrane translocation are induced in the first phase, these findings indicate the presence of a stress response specific to accumulation of secretory protein precursors in the cytoplasm. PMID- 7982956 TI - Potential convergence of insulin and cAMP signal transduction systems at the phosphoenolpyruvate carboxykinase (PEPCK) gene promoter through CCAAT/enhancer binding protein (C/EBP). AB - Adenosine 3',5'-monophosphate (cAMP) stimulates phosphoenolpyruvate carboxykinase (PEPCK) gene transcription, whereas insulin has the opposite effect. In H4IIE cells, the effect of insulin is dominant since it represses cAMP-stimulated transcription. Discrete cis-acting elements in the PEPCK promoter that serve as an insulin response sequence (IRS) and cAMP response element (CRE) have been identified. Here we show that common proteins can bind both elements, since: (i) an almost identical pattern of protein binding is seen when oligonucleotides representing either the IRS or the CRE are used as the labeled probe in a gel retardation assay and (ii) the unlabeled wild-type, but not mutated, CRE oligonucleotide competes for protein binding to the labeled IRS probe, and vice versa. Six homo- and heterodimer complexes interact with these DNA elements; the complexes are composed of three individual protein species: (a) 42-kDa C/EBP alpha, (b) 30-kDa C/EBP alpha, and (c) an unidentified 20-kDa factor termed p20- CRE/IRS Binding Protein (p20-C/IBP). These proteins have a 30-fold greater affinity for the CRE at room temperature, a difference explained by the rapid dissociation rate of protein bound to the IRS, since the association rate of protein binding to both the IRS and CRE is the same. Protease digestion experiments suggest that the proteins bind to the CRE and IRS in different conformations. The IRS and CRE both function in the context of a heterologous promoter to mediate effects of insulin and cAMP, respectively, but, although the PEPCK IRS and CRE bind common proteins, the PEPCK CRE is not a functional IRS and the PEPCK IRS is not a functional CRE. PMID- 7982957 TI - Rapid activation of post-hepatectomy factor/nuclear factor kappa B in hepatocytes, a primary response in the regenerating liver. AB - The liver represents one of the few organs in the intact animal that has the capacity to regenerate following injury or partial hepatectomy. One of the earliest responses that has been detected in the remnant liver is the activation of post-hepatectomy factor(s) (PHF), a kappa B site DNA binding activity. We reasoned that understanding the molecular nature of PHF might provide insight into what triggers liver regeneration. We found that PHF is rapidly activated and turned over in the regenerating liver, demonstrating peak activity at 30 min post hepatectomy and virtual disappearance by 1 h. As determined by supershift, cross linking, and cross-linking/immunoprecipitation analyses, PHF contains intact p50/p65nuclear factor kappa B (NF-kappa B) subunits. To explore the basis for activation of PHF/NF-kappa B in the regenerating liver, we determined the level of individual Rel family subunits in the nuclei of normal and regenerating liver cells. We found evidence for nuclear translocation of p65/RelA, but other Rel family proteins including p50/NF-kappa B1 and p52/NF-kappa B2 are present at a low level in the nuclei of cells at a constitutive level pre- and post hepatectomy and appear not to form DNA binding homodimers. The level of I kappa B alpha falls slightly then increases at 3 h post-hepatectomy in concert with the induction of its mRNA. As demonstrated by the induction of I kappa B-alpha mRNA in hepatocytes in situ and identification of PHF/NF-kappa B in cultured hepatocytes, PHF/NF-kappa B is localized primarily in hepatocytes in the regenerating liver. This represents one of the few examples of NF-kappa B activation in the intact animal in a non-hematopoietic cell type. The activation of PHF/NF-kappa B suggests a mechanism by which hepatocytes regulate their mitogenic program during liver regeneration. PMID- 7982958 TI - Conformation-dependent phosphorylation of Na,K-ATPase by protein kinase A and protein kinase C. AB - Phosphorylation of sodium and potassium ion-activated adenosine triphosphatase (Na,K-ATPase) by protein kinase A (PKA) and protein kinase C (PKC) was investigated in vitro, where substrate conformation, kinase activity, and consequent effects on Na,K-ATPase activity could be controlled. With Na, K-ATPase from rat kidney, optimal stoichiometries were close to 1 mol 32P/mol Na,K-ATPase for both kinases. Addition of Na+, K+, P(i), or ouabain is known to stabilize the Na,K-ATPase in different states and was found to affect phosphorylation by the two kinases in a reciprocal way. This indicates that exposure of the phosphorylation sites varies with conformation and suggests a structural basis for the variable responses to kinase activation in intact cells. Further evidence for the importance of Na,K-ATPase conformation in its interaction with kinase came from the autophosphorylation of PKC, which varied in proportion to both the concentration and conformation of rat Na,K-ATPase. With pig and dog Na,K-ATPase, little phosphorylation by PKC was detected, and yet the PKC phosphorylated itself when the Na,K-ATPase was in the optimal conformation. The location of the PKA phosphorylation site was confirmed to be Ser-938 by sequence analysis of a tryptic peptide. Effects of PKA on Na,K-ATPase activity could not be measured because of inhibition by the Triton X-100 needed to obtain phosphorylation. Phosphorylation by PKC, even in optimal conditions, failed to result in inhibition of Na,K-ATPase activity. This suggests that any physiological role of phosphorylation either entails a subtle modulation of enzyme properties, or requires additional regulatory proteins. PMID- 7982959 TI - The role of NFATp in cyclosporin A-sensitive tumor necrosis factor-alpha gene transcription. AB - The tumor necrosis factor-alpha (TNF alpha) gene is an immediate early gene in activated T cells, in that it is rapidly induced without a requirement for protein synthesis. Maximal induction of TNF alpha mRNA can be induced by treatment of T cells with calcium ionophores alone, via a calcineurin-dependent process that is blocked by cyclosporin A. We have previously identified a promoter element, kappa 3, that is required for calcium-stimulated, cyclosporin A sensitive induction of the TNF alpha gene in activated T cells. Here, we demonstrate that the kappa 3 binding factor contains NFATp, a cyclosporin sensitive DNA-binding protein required for interleukin-2 gene transcription. NFATp binds to two sites within the kappa 3 element, and occupancy of both sites is required for TNF alpha gene induction. Thus, although the kappa 3 element has little sequence similarity to other NFATp-binding sites, it appears to function as a cyclosporin-sensitive promoter element in T cells by virtue of its ability to bind NFATp. The involvement of NFATp in transcriptional activation of both the interleukin-2 and TNF alpha genes suggests that this factor plays an important role in the coordinate induction of multiple cytokine genes, starting at the earliest stages of T cell activation. PMID- 7982960 TI - Induction of cholinergic differentiation with neurite sprouting by de novo biosynthesis and expression of GD3 and b-series gangliosides in Neuro2a cells. AB - The expression of a single glycosyltransferase, GD3 synthase, caused cholinergic differentiation with neurite sprouting. The cells that expressed GD3 were established from Neuro2a cells by transfection of a mammalian expression vector into which were carried a cDNA encoding GD3 synthase and the blasticidin-S deaminase gene with a SV40 promoter, followed by selection with blasticidin-S hydrochloride. The blasticidin-S-hydrochloride-resistant colonies derived from the cells transfected with the cDNA encoding GD3 synthase and the clonal cells (N2a-GD3) were spontaneously sprouting neurites but not those derived from cells transfected with only the vector without the cDNA encoding GD3 synthase (N2a bsr). GD3 expression by N2a-GD3 was confirmed by immunostaining of the cells using the anti-GD3 monoclonal antibody, KM643. N2a-GD3 expressed not only GD3 but also GQ1b, one of the b-series gangliosides, whereas N2a-bsr did not express these gangliosides. Cell proliferation of N2a-GD3 was greatly reduced, as compared with that of N2a-bsr, and, after several passages, it completely stopped. In addition, N2a-GD3 expressed acetylcholine esterase, indicating that the differentiation of Neuro2a cells was induced by expression of GD3 synthase and subsequent modification of the biosynthesis and expression of gangliosides. These results strongly suggest that the de novo synthesis and expression of GD3 and/or b-series gangliosides induce neurite outgrowth and differentiation of Neuro2a cells. Exogenous GM1 stimulated the neuritogenesis of N2a-bsr but not differentiated N2a-GD3, indicating that the mechanism of neurite sprouting in this system may be overlapped en route with that of exogenous GM1. PMID- 7982961 TI - Active recombinant rat calpain II. Bacterially produced large and small subunits associate both in vivo and in vitro. AB - cDNA for the C-terminal Ca(2+)-binding domain of rat calpain small subunit was cloned by means of the polymerase chain reaction. The encoded protein (21 kDa), which corresponds closely to the natural autolysis product of the small subunit, was produced in soluble form in Escherichia coli at a level of 20 mg/liter of cell culture. Rat calpain II large subunit (80 kDa) was produced from a cDNA clone in E. coli in soluble form at a level of approximately 1 mg/liter. The 80 kDa subunit alone had no proteinase activity, with or without Ca2+, but Ca(2+) dependent proteinase activity was obtained following association of the two subunits, which was achieved either by co-expression of the two subunit cDNAs in E. coli, or by mixing the two partially purified subunits in the presence of 1 M NaSCN followed by dialysis. The heterodimeric (80 + 21 kDa) proteinase had a Ca2+ requirement for 50% activity of 0.35 mM and a specific activity at 2 mM Ca2+ of approximately 1 unit/microgram, values essentially identical to those of natural (80 + 30 kDa) calpain II. The results establish association and biological activity of the bacterially produced subunits and provide a system for studying structure-function relationships in calpain by means of mutagenesis. PMID- 7982962 TI - Purification of a serine kinase that associates with and phosphorylates human Cdc25C on serine 216. AB - Human Cdc25C is a protein phosphatase that dephosphorylates and activates Cdc2 cyclin B to trigger entry into mitosis. Cdc25C is itself regulated by phosphorylation. In asynchronously growing HeLa cells, we have determined that serine 216 is the major site of Cdc25C phosphorylation. We have isolated a protein kinase that binds to Cdc25C and phosphorylates serine 216. The kinase binds within amino acids 200-256 of Cdc25C. This region is conserved in some Cdc25 homologues and contains a putative bipartite nuclear localization signal just downstream from serine 216. Finally, the Cdc25C-associating kinase was purified over 8000-fold from rat liver as a 36-38-kDa doublet of proteins. PMID- 7982963 TI - Common and divergent peptide binding specificities of hsp70 molecular chaperones. AB - We have studied the binding of synthetic peptides to three hsp70 molecular chaperones, DnaK, BiP, and hsc70, as a model for the interaction of hsp70 proteins with unfolded regions of target polypeptides. We measured the ability of 53 peptides to inhibit the formation of complexes between the hsp70 proteins and denatured lactalbumin. Peptides that bound with highest affinity to all three hsp70 proteins contained stretches of at least 7 residues that included large hydrophobic and basic amino acids, but few or no acidic residues. Amino acid substitutions within one heptameric peptide showed that an important feature for its binding to all three chaperones was a large hydrophobic residue in position 4, while specificity differences between the chaperones were revealed by substitutions at positions 2 and 6. Such specificity differences were frequently observed with other peptides, the most extreme example being a peptide rich in basic residues that bound with high affinity to DnaK, intermediate affinity to hsc70, and negligible affinity to BiP. Substitution of a lysine residue at position 2 in this peptide by tyrosine abolished the specificity difference by increasing the affinities of the DnaK and hsc70 proteins 5- and 20-fold, respectively, and that of BiP by greater than 2 orders of magnitude. Thus, hsp70 proteins can exhibit common or exclusive binding specificities, depending on the peptide sequence. PMID- 7982964 TI - cDNA cloning of the human tumor motility-stimulating protein, autotaxin, reveals a homology with phosphodiesterases. AB - A human cDNA clone encoding autotaxin, a tumor cell motility-stimulating protein, reveals that this protein is an ecto/exo-enzyme with significant homology to the plasma cell membrane differentiation antigen PC-1. ATX is a 125-kDa glycoprotein, previously isolated from a human melanoma cell line (A2058), which elicits chemotactic and chemokinetic responses at picomolar to nanomolar concentrations. Affinity-purified antipeptide antibodies to the ATX peptide, ATX-102, were employed to screen an A2058 cDNA expression library made in lambda gt11. The partial cDNA sequence which was obtained was then extended by utilizing reverse transcriptase on total cellular RNA followed by polymerase chain reaction amplification. The isolated cDNA clone contained 3251 base pairs, and the mRNA message size was approximately 3.3 kilobases. The deduced amino acid sequence of autotaxin matched 30 previously sequenced peptides and comprised a protein of 915 amino acids. Data base analysis of the ATX sequence revealed a 45% amino acid identity (including 30 out of 33 cysteines) with PC-1, a pyrophosphatase/type I phosphodiesterase expressed on the surface of activated B cells and plasma cells. ATX, like PC-1, was found to hydrolyze the type I phosphodiesterase substrate p nitrophenyl thymidine-5'-monophosphate. Autotaxin now defines a novel motility regulating function for this class of ecto/exo-enzymes. PMID- 7982965 TI - Wortmannin inhibits mitogen-activated protein kinase activation induced by platelet-activating factor in guinea pig neutrophils. AB - Stimulation of guinea pig neutrophils with platelet-activating factor (PAF) caused a rapid and transient activation of mitogen-activated protein kinase (MAPK). Wortmannin, an inhibitor of phosphatidylinositol 3-kinase, partially (approximately 50%) inhibited PAF-induced MAPK activation. Half-maximal inhibition was observed with 200-300 nM wortmannin, while it did not inhibit phorbol ester-induced MAPK activation. Neutrophils preloaded with 1,2-bis-(O aminophenoxy)ethane-N,N,N',N'-tetraacetic acid acetoxymethyl ester (BAPTA/AM) failed to raise cytosolic Ca2+ concentrations toward PAF, while they still responded to PAF with a 40-50% activation of MAPK. However, when cells were treated with BAPTA/AM and wortmannin in combination, the MAPK activation was completely inhibited. These results suggest that PAF activates MAPK through two distinct pathways in guinea pig neutrophils, one Ca(2+)-dependent, and the other Ca(2+)-independent but wortmannin-sensitive. PMID- 7982966 TI - DNA glycosylase activities for thymine residues oxidized in the methyl group are functions of the AlkA enzyme in Escherichia coli. AB - The alkA gene of Escherichia coli encodes a DNA glycosylase involved in base excision repair of DNA alkylation damage. In an attempt to define the reactions of the AlkA enzyme with methylated DNA, we discovered that the enzyme released substantial amounts of radioactivity from [methyl-3H]thymidine-labeled DNA even without any exposure of the DNA to methylating agents. The excised material was identified by chromatography as two different oxidized derivatives of thymine, 5 hydroxymethyluracil and 5-formyluracil. These products are formed in such DNA by one and two consecutive decays, respectively, of the tritiums of the labeled methyl group. Kinetic analysis showed that both the apparent Km and Vmax values for 5-formyluracil removal are within the same range as found for 3-methyladenine removal, suggesting that this catalytic property of AlkA is also significant under in vivo conditions. Removal of 5-hydroxymethyluracil proceeds at a rate that is 1-3 orders of magnitude slower. Since both 5-formyluracil and 5 hydroxymethyluracil are major products formed in DNA by exposure to ionizing radiation, these results implicate the alkA gene function also in the repair of oxidative DNA damage. Neither of the two other enzymes involved in the repair of oxidative DNA damage in E. coli, i.e. endonuclease III and formamidopyrimidine DNA glycosylase, has any affinity for oxidized unsaturated pyrimidines in DNA. PMID- 7982967 TI - Phosphorylation and expression of connexin-43 ovarian gap junction protein are regulated by luteinizing hormone. AB - One important role of the junctional communication in the ovarian follicle is to mediate transmission of cAMP, the regulatory signal that maintains the oocyte in meiotic arrest. Luteinizing hormone (LH) interrupts cell-to-cell communication within the ovarian follicle, leading to a decrease in intraoocyte concentrations of cAMP followed by resumption of meiosis. Our experiments were directed at exploration of mechanisms involved in the LH-induced communication breakdown in the preovulatory ovarian follicle. Immunofluorescence and Western blot analysis, using highly specific antibodies, showed that connexin-43 (Cx43), the ovarian gap junction protein, is present in the cytoplasmic membranes of the follicular cells in multiple phosphorylated forms. The relative amounts of the different forms of Cx43 vary in response to LH: short time exposure (10 min) stimulated phosphorylation of Cx43 followed by immediate dephosphorylation, while longer incubations (8 and 24 h) with this hormone resulted in elimination of the protein. Forskolin mimicked the LH-induced phosphorylation/dephosphorylation, as well as the decrease of Cx43 protein level. A gonadotropin-releasing hormone analog (GnRHa) also induced an immediate phosphorylation/dephosphorylation of Cx43 and a later reduction of the amount of Cx43. The direct PKC activator, 12-O tetradecanoylphorbol-13-acetate (TPA), induced phosphorylation of Cx43 that was completely blocked by the protein kinase C inhibitor, staurosporine. This kinase inhibitor partially interfered with LH, but not forskolin-induced phosphorylation of Cx43. Analysis of the effect of LH on Cx43 gene expression revealed a significant decrease (45%) in Cx43 mRNA level at 24 h of incubation. A drop of Cx43 mRNA was also induced by GnRHa. Our results suggest that the LH-induced gating mechanism of the gap junctions in rat ovarian follicles is comprised of two steps: the immediate response is represented by a change in the phosphorylation state of the Cx43 protein, and the later response is manifested by a reduction of Cx43 protein level, due to attenuation of its gene expression. Phosphorylation of Cx43 may occur through PKA-, as well as PKC-dependent pathways. PMID- 7982968 TI - Isolation and characterization of the THI6 gene encoding a bifunctional thiamin phosphate pyrophosphorylase/hydroxyethylthiazole kinase from Saccharomyces cerevisiae. AB - Thiamin-phosphate pyrophosphorylase (TMP-PPase; EC 2.5.1.3) involved in de novo synthesis of thiamin in Saccharomyces cerevisiae is a bifunctional enzyme with 4 methyl-5-beta-hydroxyethylthiazole kinase (Th-kinase; EC 2.7.1.50) activity, which is an octamer of identical 60-kDa subunits (Kawasaki, Y. (1993) J. Bacteriol. 175, 5153-5158). Previous study demonstrated that the activities of both TMP-PPase and Th-kinase are reduced by the mutation of a single nuclear gene, designated THI6. We have cloned the THI6 gene from a yeast genomic library by functional complementation of the thi6 mutant and determined by DNA blot analysis that THI6 is located on chromosome XVI. The nucleotide sequence of the THI6 gene contained an open reading frame of 1,620 base pairs encoding a 540 amino acid polypeptide with a calculated molecular weight of 58,058, which is similar to the determined molecular mass of the purified bifunctional enzyme. Gene disruption demonstrated that the thi6 null strain is auxotrophic for thiamin, indicating that the THI6 protein is essential for thiamin synthesis in yeast. A recently isolated thi6 mutant, thi6-3, bearing a replacement of Glu370 by Lys370, showed a decrease in only Th-kinase activity, proving that the THI6 gene of S. cerevisiae encodes a structural gene of the thiamin biosynthetic bifunctional enzyme. Furthermore, complementation analysis of the thi6 null strain with the modified THI6 DNAs by a 12-nucleotide linker insertion suggested that a region from amino acids 138 to 187 and that from amino acids 370 to 453 are involved in functional domains of TMP-PPase and Th-kinase, respectively, whereas the COOH-terminal region is necessary for both enzyme activities. Strains conferring no Th-kinase but slight TMP-PPase activity could grow in medium without thiamin, suggesting that 4-methyl-5-beta-hydroxyethylthiazole is not involved in the pathway of de novo synthesis of thiamin via 4-methyl-5-beta hydroxyethylthiazole monophosphate. Northern blot analysis demonstrated that THI6 gene expression is regulated at the mRNA level by intracellular thiamin pyrophosphate, a coenzyme form of thiamin, and that it requires the positive regulatory factors encoded by the THI2 and THI3 genes. PMID- 7982969 TI - The delta-subunit of murine guanine nucleotide exchange factor eIF-2B. Characterization of cDNAs predicts isoforms differing at the amino-terminal end. AB - Protein synthesis in mammalian cells is regulated at the level of the guanine nucleotide exchange factor, eIF-2B, which catalyzes the exchange of eukaryotic initiation factor 2-bound GDP for GTP. We have isolated and sequenced cDNA clones encoding the delta-subunit of murine eIF-2B. The cDNA sequence encodes a polypeptide of 544 amino acids with molecular mass of 60 kDa. Antibodies against a synthetic polypeptide of 30 amino acids deduced from the cDNA sequence specifically react with the delta-subunit of mammalian eIF-2B. The cDNA-derived amino acid sequence shows significant homology with the yeast translational regulator Gcd2, supporting the hypothesis that Gcd2 may be the yeast homolog of the delta-subunit of mammalian eIF-2B. Primer extension studies and anchor polymerase chain reaction analysis were performed to determine the 5'-end of the transcript for the delta-subunit of eIF-2B. Results of these experiments demonstrate two different mRNAs for the delta-subunit of eIF-2B in murine cells. The isolation and characterization of two different full-length cDNAs also predicts the presence of two alternate forms of the delta-subunit of eIF-2B in murine cells. These differ at their amino-terminal end but have identical nucleotide sequences coding for amino acids 31-544. PMID- 7982970 TI - Lysyl hydroxylase, a collagen processing enzyme, exemplifies a novel class of luminally-oriented peripheral membrane proteins in the endoplasmic reticulum. AB - Lysyl hydroxylase (LH), an enzyme required early during collagen biosynthesis, appears to be exceptional among proteins that are thought to be residents of the endoplasmic reticulum (ER). It is a homodimer and does not contain either of the two previously characterized ER-specific retention motifs (KDEL or the double lysine motif) in its primary structure. We now show that LH, nevertheless, resides in the lumen of the ER. In immunofluorescence experiments, LH co localizes with a KDEL-containing protein, protein disulfide isomerase (PDI), and also co-sediments with it after fractionation of subcellular organelles by sucrose density gradient centrifugation. In addition, LH seems to be stress inducible. In one respect, however, LH differs from PDI and other known luminal proteins in the organelle. It is found in situ only in association with the ER membranes. Our cell fractionation and Triton X-114 phase separation experiments suggest that it binds to the membranes via weak electrostatic interactions. LH can thus be regarded as a first luminally-oriented "peripheral membrane" protein which has been characterized in the ER. The results suggest a novel possibility by which ER lumen can acquire its specific protein components from the bulk flow. PMID- 7982971 TI - mik1+ encodes a tyrosine kinase that phosphorylates p34cdc2 on tyrosine 15. AB - mik1+ and wee1+ function to regulate the tyrosine phosphorylation of p34cdc2 in Schizosaccharomyces pombe (Lundgren, K., Walworth, N., Booher, R., Dembski, M., Kirschner, M., and Beach, D. (1991) Cell 64, 1111-1122). wee1+ encodes a tyrosine kinase that directly phosphorylates p34cdc2 on tyrosine 15, resulting in the inactivation of the cyclin B/p34cdc2 complex. We have overproduced the mik1+ gene product in insect cells and in S. pombe in order to characterize it biochemically. Immunoprecipitates of Mik1 from both sources catalyzed the phosphorylation of p34cdc2 on tyrosine 15 whereas immunoprecipitates of a kinase deficient mutant of Mik1 were negative in this assay. Mik1 overproduced in insect cells was partially purified by column chromatography, and column fractions were assayed for their ability to phosphorylate p34cdc2 on tyrosine 15. Two major peaks of Mik1 protein were detected by gel filtration chromatography. One peak eluted in the void volume, and a second peak eluted with an apparent molecular mass expected for monomeric Mik1 (approximately 68 kDa). The tyrosine 15 kinase activity co-eluted with the 68 kDa form of Mik1. These results indicate that mik1+ encodes a tyrosine kinase that directly phosphorylates p34cdc2 on tyrosine 15. PMID- 7982972 TI - Identification of functional promoter elements in the rabbit smooth muscle myosin heavy chain gene. AB - Despite the importance of smooth muscle cell proliferation in vascular pathophysiological states, the mechanisms regulating smooth muscle cell growth and differentiation are poorly understood. Previous studies have shown that adult rabbit smooth muscles express two types of myosin heavy chain (MHC) isoforms, SM1 and SM2, which are generated through alternative RNA splicing from a single smooth muscle MHC (SMHC) gene. In the present study, we isolated and characterized the rabbit SMHC gene promoter. DNA sequence analysis of the upstream region of the SMHC gene revealed several putative cis-DNA regulatory elements proximal to the transcription start site. Most notably, cis-acting regulatory elements that closely resemble CC(A/T)6GG (CArG box) and myocyte enhancer binding factor 2 (MEF-2)-type sequence motifs were found in the SMHC 5' flanking region. In addition, six E-box motifs were found in the 5'-flanking region of the SMHC gene between -374 and -2109 base pairs from the transcription start site. A series of transient transfection assays using SMHC promoter deletion constructs indicated that a promoter fragment extending to 2266 base pairs upstream of the transcription start site has the highest reporter activity in cultured rat aortic smooth muscle cells. Gel mobility shift analyses using the MEF-2-like sequence located at -1540 revealed a specific DNA protein complex, whereas the CArG-like element located at -1275 did not show protein binding. The SMHC promoter construct, p509-CAT, which included neither the CArG- nor MEF-2 type motifs, conferred 32% of chloramphenicol acetyltransferase activity in the same cells, whereas the construct p188-CAT, which contained the minimal promoter elements (TATA box), was significantly less active (7%; 2.0-fold over background). This is the first report describing the promoter elements of a gene whose expression is restricted to smooth muscle cells. PMID- 7982973 TI - Differences in signal transduction between platelet-derived growth factor (PDGF) alpha and beta receptors in vascular smooth muscle cells. PDGF-BB is a potent mitogen, but PDGF-AA promotes only protein synthesis without activation of DNA synthesis. AB - Cultured vascular smooth muscle cells (VSMC) from spontaneously hypertensive rats express both alpha and beta isoforms of the platelet-derived growth factor (PDGF) receptors at high levels (100,000 and 240,000 sites/cell, respectively). In this cell type, PDGF-BB elicited a mitogenic response; however, PDGF-AA increased only protein synthesis without activating DNA synthesis. Protein kinase C (PKC) was activated by PDGF-AA as well as PDGF-BB with concomitant translocation from cytosol to membrane fractions. However, the hypertrophic effect of PDGF-AA was not affected by depletion of cellular PKC, whereas the mitogenic action of PDGF BB was partially attenuated by the depletion. Following incubation with PDGF-AA or -BB, phospholipase C-gamma 1 (PLC-gamma 1) and phosphatidylinositol 3-kinase were tyrosine phosphorylated; however, the phosphorylation of Ras-GTPase activating protein was induced only by PDGF-BB. Both PDGF isoforms resulted in a prompt and transient increase in the level of 1,2-diacylglycerol (DAG), presumably through the action of PLC-gamma 1. After returning to basal levels, the rate of DAG synthesis steadily increased for at least 15 min due to activation of phosphatidylcholine-hydrolyzing phospholipase C (PC-PLC). Incubation with PDGF-BB-activated phospholipase D (PLD) in a PKC-dependent manner resulting in the formation of phosphatidic acid (PA). PA was also formed by the sequential reactions of PC-PLC and DAG kinase in the PDGF-BB-stimulated VSMC, and these sequential reactions were not affected by PKC depletion. In contrast, PDGF AA stimulation did not result in increased PA synthesis as neither PLD nor DAG kinase activities were affected. PA may be a significant second messenger in the activation of DNA synthesis by PDGF-BB. These results indicate that signaling mechanisms of the PDGF-alpha and -beta receptors in VSMC are distinctly different in signal transduction in VSMC and that the alpha receptor promotes cellular hypertrophy (but not hyperplasia), whereas a mitogenic response is mediated only through the beta receptor. PMID- 7982974 TI - Different prooxidant levels stimulate growth, trigger apoptosis, or produce necrosis of insulin-secreting RINm5F cells. The role of intracellular polyamines. AB - Increasing concentrations (1-100 microM) of the redox cycling quinone, 2,3 dimethoxy-1,4-naphthoquinone (DMNQ), stimulated growth, triggered apoptosis, or caused necrosis of pancreatic RINm5F cells, depending on the dose and duration of the exposure. Following the exposure of RINm5F cells to 10 microM DMNQ, ornithine decarboxylase activity and polyamine biosynthesis increased. This was accompanied by enhanced cell proliferation. Conversely, exposure to 30 microM DMNQ for 3 h resulted in the inhibition of ornithine decarboxylase, intracellular polyamine depletion, and apoptotic cell killing. Pretreatment of the cultures with the phorbol ester, 12-O-tetradecanoylphorbol-13-acetate, restored polyamine levels and prevented apoptosis. Exposure to the same DMNQ concentration for only 1 h, with subsequent re-incubation in growth medium, neither caused polyamine depletion nor resulted in apoptosis. Finally, exposure to an even higher DMNQ concentration (100 microM) for either 1 or 3 h caused rapid intracellular Ca2+ overload, ATP, NAD+, and glutathione depletion, and extensive DNA single strand breakage, which resulted in necrotic cell death. Our results show that a disturbance of polyamine biosynthesis occurred prior to cell growth or apoptosis elicited by oxidative stress. In addition, we show that effects as opposite as cell proliferation and deletion, by either apoptosis or necrosis, can be induced, in the same system, by varying the exposure to a prooxidant. PMID- 7982975 TI - The binding of immobilized IgG2a to Fc gamma 2a receptor activates NF-kappa B via reactive oxygen intermediates and tumor necrosis factor-alpha 1. AB - The macrophage-like cell line, J774, was found to respond to immobilized mouse monoclonal IgG2a proteins, but not to soluble forms of IgG2a or IgG2b or to immobilized F(ab')2 of IgG2a, by the increase in the nuclear proteins of two different types of NF-kappa B proteins which differed in their electrophoretic mobilities. Fc gamma 2a receptor-mediated activation of NF-kappa B was blocked by the presence of pyrrolidinedithiocarbamate, neutralizing anti-tumor necrosis factor (TNF)-alpha antibodies, various protein kinase inhibitors (H-89, genistein, or heparin) or intracellular calcium chelator (1,2-bis(O-aminophenoxy) ethane-N,N,N',N'-tetraacetic acid tetra-(acetoxymethyl)-ester, BAPTA/AM) during stimulation. J774 cells were also found to respond to immobilized IgG2a, but not IgG2b, by the increased production of superoxide, H2O2, and TNF-alpha. Fc gamma 2aR-induced production of H2O2 was inhibited by pretreatment of the cells with pyrrolidinedithiocarbamate, H-89, genistein, heparin, or BAPTA/AM, but not with anti-TNF-alpha antibody. Fc gamma 2aR-induced production of TNF-alpha was, on the other hand, not inhibited by pretreatment of the cells with BAPTA/AM. Although J774 cells responded to exogenously added rTNF-alpha, but not to H2O2, by activation of NF-kappa B, the recombinant TNF-alpha-mediated NF-kappa B activation was enhanced by simultaneous presence of H2O2. These results thus suggest that macrophages respond to the stimulation of Fc gamma 2aR by the production of both reactive oxygen intermediates and TNF-alpha and that endogenous TNF-alpha activates NF-kappa B via the pathway involving reactive oxygen intermediates. PMID- 7982976 TI - Characterization of sua7 mutations defines a domain of TFIIB involved in transcription start site selection in yeast. AB - The SUA7 gene of Saccharomyces cerevisiae encodes the general transcription factor TFIIB. SUA7 was identified based on the ability of mutations at this locus to shift transcription start site selection at the cyc1 gene downstream of normal. Here, we report the nature of these mutations; the sua7-1 and sua7-2 alleles encode identical E62K replacements, and sua7-3 encodes an R78C replacement. Both Glu-62 and Arg-78 are phylogenetically invariant and occur within the most highly conserved region of TFIIB, immediately distal to a zinc finger motif. A double E62K,R78C mutant was constructed and exhibited the same phenotypes associated with the single mutants, including cold sensitivity and altered start site selection, suggesting that Glu-62 and Arg-78 are functionally related. This observation, and the opposite charge of the 2 residues, suggested that Glu-62 and Arg-78 might interact to form a salt bridge. This was tested by constructing reciprocal E62R and R78E replacements. The E62R mutant is phenotypically identical to the E62K mutant, whereas the R78E mutant is inviable. However, an E62R,R78E double mutant was not only viable but is phenotypically similar to the single mutants. These results define the highly conserved sequence adjacent to the zinc finger of TFIIB as a critical determinant of start site selection and suggest that an Glu-62-Arg-78 salt bridge is an important structural element of that domain. PMID- 7982977 TI - Raf-1 kinase activity is necessary and sufficient for gene expression changes but not sufficient for cellular morphology changes associated with cardiac myocyte hypertrophy. AB - Around the time of birth, cardiac muscle cells lose the capacity to divide and, from this time on, growth of the heart occurs by hypertrophy where each cells gets bigger. The hypertrophic response is characterized by changes in gene expression including expression of the atrial natriuretic factor (ANF) and myosin light chain-2 (MLC-2) genes. In cultured neonatal ventricular myocytes, hypertrophy also involves reorganization of contractile proteins into sarcomeric units. We have investigated the role of the Raf-1 kinase in this response. Activation of an estradiol-regulated Raf-1 protein kinase led to activation of mitogen-activated protein (MAP) kinase and activated expression from the ANF and MLC-2 promoters. Raf-1-induced activation of these genes was inhibited by a kinase deficient mutant of the 44-kDa MAP kinase, Erk1 indicating a requirement for MAP kinases in the Raf-1-induced response. However, activation of Raf-1 was not sufficient to induce the organization of actin into sarcomeric units. Transfection of dominant negative Raf-1 inhibited phenylephrine-induced activation of the ANF and MLC-2 promoters. Transactivation was rescued by the introduction of increased amounts of c-Raf suggesting a role for Raf-1 in the response to alpha-adrenergic agonists. These results suggest that activation of Raf-1 kinase is a critical component of the signal transduction pathway leading to changes in gene expression associated with hypertrophy but that Raf-1 is not sufficient for the regulation of actin organization during the hypertrophic response. PMID- 7982978 TI - Characterization of cis-regulating elements and trans-activating factors of the rat cardiac troponin T gene. AB - To study the transcriptional regulation of the rat cardiac troponin T (cTnT) gene, chimeric genes composed of the upstream region (-757 to +193 base pairs (bp) relative to the transcription initiation site) of the cTnT gene and the bacterial chloramphenicol acetyltransferase (CAT) gene were constructed and transfected into primary cultures of neonatal cardiomyocytes and cardiac fibroblasts. Deletion analysis showed that a 41-bp fragment (-249 to -209 bp) containing the MEF-2-like motif is an essential element for minimal cardiac specific expression of the rat cTnT gene. The proximal promoter (-208 to -1 bp) contains two consensus CArG boxes, one M-CAT motif, one AP2 site, and one TATA box. The construct (cTNT-208) composed of the CAT reporter gene driven by this proximal promoter did not show cardiac muscle-specific expression. Ligation of consensus MEF-2-like sequence into the upstream of this chimera only partially increased its ability to express in cardiomyocytes. These results suggest that the spacing among MEF-2-like motif and proximal promoter and/or the flanking sequences of the MEF-2-like motif are important in determining cardiac muscle specific expression. By footprint analysis with a DNA fragment (-303 to +6 bp), we identified three novel regions (called A, B, and C) protected by protein extract from rat hearts, in addition to the known motifs such as MEF-2, M-CAT, and CArG. Gel retardation with the probe (-235 to -141 bp), containing the MEF-2 like motif, one of the CArG boxes, and the C region, or the 41-bp probe (-249 to 209 bp), containing the MEF-2-like motif, revealed different DNA-protein complexes formed by heart, skeletal muscle, and liver extracts. By using DNA affinity purification, DNA-binding proteins with apparent molecular masses of 22 26 kDa were identified from rat heart extract but not from skeletal and liver extracts, suggesting the involvement of cardiac-specific proteins in regulating the cTnT gene expression. PMID- 7982979 TI - Platelet-derived growth factor (PDGF) B and A homodimers transform murine fibroblasts depending on the genetic background of the cell. AB - The endogenously overexpressed c-sis (platelet-derived growth factor (PDGF) B chain) proto-oncogene and its viral counterpart v-sis effectively transform NIH 3T3 cells by an autocrine mechanism, whereas the PDGF A-chain gene does not. However, PDGF B continuously cultured with confluent NIH 3T3 cells fails to induce phenotypic transformation as would be predicted by the autocrine model. We now have established conditions in which subconfluent, logarithmically growing NIH 3T3 cells are efficiently transformed by exogenous PDGF B but not PDGF A. Clonally selected cells from transformed foci remain transformed when continuously cultured with PDGF B but revert to the non-transformed phenotype without PDGF B or if PDGF A is substituted for PDGF B, suggesting that PDGF B complements a genetically stable NIH 3T3 cell phenotype to induce transformation and initiates a signal different from that of PDGF A required to induce transformation. Neither PDGF A nor PDGF B transform normal rat kidney (NRK) cells under identical conditions of culture. However, we now demonstrate that exogenous PDGF A and PDGF B independently transform NRK cells that endogenously overexpress the anti-apoptotic bcl-2 gene. These results suggest that both PDGF A and PDGF B effectively transform murine fibroblasts with a compatible genotype, that transformation by the PDGF isoforms requires complementation with a compatible genotype in a multistep transformational process, and that the autocrine mechanism is required but not sufficient for transformation of murine fibroblasts by PDGF. PMID- 7982980 TI - The beta-interferon promoter responds to priming through multiple independent regulatory elements. AB - The induction of beta-interferon is markedly enhanced in some cell types by a pretreatment with type I interferon itself (priming). We show that induction in response to double-stranded RNA is completely dependent upon priming in HeLa cells. However, unprimed cells can be partially induced by Sendai virus. This indicates that Sendai virus can provide a signal that is different from, or additional to, that provided by double-stranded RNA. The requirement for priming cannot be localized to a specific sequence element in the beta-interferon promoter, suggesting that priming may induce an essential component for signal transduction in response to double-stranded RNA. PMID- 7982981 TI - In vitro study of functional involvement of Sp1, NF-kappa B/Rel, and AP1 in phorbol 12-myristate 13-acetate-mediated HIV-1 long terminal repeat activation. AB - We examined the cooperative activity between the Sp1 and NF-kappa B/Rel sites of the human immunodeficiency virus type 1 long terminal repeat in response to phorbol 12-myristate 13-acetate (PMA) stimulation in an in vitro transcription assay. Sp1 sites alone do not account for the activation induced by PMA. When mutations in Sp1 sites were combined with mutations in the NF-kappa B/Rel sites, a dramatic reduction in PMA-induced transcriptional activity was observed. This reduction was much greater than the reduction associated with mutations involving only the NF-kappa B/Rel sites. This finding suggests that there is functional cooperation between Sp1 and NF-kappa B/Rel and that this is one possible mechanism for transcription activation by NF-kappa B/Rel. The three AP1 sites in the negative regulatory region of the long terminal repeat, however, seem to be uninvolved in the earliest moments of transcriptional activation by PMA. PMID- 7982982 TI - Spliced leader-associated RNA of trypanosomes. Sequence conservation and association with protein components common to trans-spliceosomal ribonucleoproteins. AB - A spliced leader-associated (SLA) RNA recently identified in Trypanosoma brucei has been proposed as a U5 RNA analog in trans-splicing, based on in vivo psoralen cross-linking to the spliced leader (SL) RNA and a short stretch of homology to a conserved U5 RNA sequence. Here we show that the SLA RNA is in the form of an RNP containing common proteins that also occur in the known trans-spliceosomal snRNPs of T. brucei, the SL, U2, and U4/U6 snRNPs. Therefore the SLA RNP is a member of a larger family of related RNPs. The immunoprecipitation of the SLA RNA by antibodies against common proteins does not require an association between the SLA RNA and the SL RNP. To identify sequences of potential functional importance and to establish a secondary structure model, we have sequenced the SLA RNA and cloned its gene from a related trypanosomatid, Leptomonas seymouri. A sequence comparison between the T. brucei and L. seymouri SLA RNAs reveals that the U5 homologous sequence element is not conserved. PMID- 7982983 TI - The phenotype of a "Cdc2 kinase target site-deficient" mutant of oncoprotein 18 reveals a role of this protein in cell cycle control. AB - Oncoprotein 18 (Op18) is a cytosolic protein that is expressed in all proliferating cells. This phosphoprotein is up-regulated in a variety of human neoplasm, and phosphorylation of its two Cdc2 kinase target sites, Ser-25 and Ser 38, fluctuates dramatically during the cell cycle. We have investigated the potential role of the Cdc2 kinase-mediated phosphorylation of these two sites by expressing a "Cdc2 kinase target site-deficient" mutant of Op18 (Op18-S25,38A), and analyzed the phenotype on the level of cell cycle regulation. The result shows that induced expression of Op18-S25,38A results in rapid accumulation of cells in the G2 phase of the cell cycle. The block in G2 seems transient, since prolonged incubation was found to result in a large fraction of the transfected cells entering S phase in the absence of mitosis, i.e. endoreduplication. In addition, a fraction (30%) of the transfected cells was blocked in mitosis. Whereas the morphology of the G2 arrested cells appeared normal, expression of Op18-S25,38A caused a serious defect during mitotic chromosome segregation. Analyses of the mechanism behind the phenotype of Op18-S25,38A suggest an essential role for Op18 during cell division and that the mutant interferes with the function of the endogenous gene product. PMID- 7982984 TI - The low affinity neurotrophin receptor, p75LNTR, is palmitoylated by thioester formation through cysteine 279. AB - The low affinity neurotrophin receptor, termed p75LNTR, plays a role in increasing the amount of nerve growth factor that becomes bound to the tyrosine kinase receptor, trkA (Barker, P. A., and Shooter, E. M. (1994) Neuron 13: 203 215), possibly by increasing the nerve growth factor concentration in the microenvironment surrounding the trkA receptor. Because protein acylation may be a means by which cell surface receptor distribution may be regulated, we have determined the acylation status of p75LNTR. We find that p75LNTR expressed in PC12, PCNA, or transfected COS cells is metabolically labeled with [3H]palmitic acid. This modification occurs post-translationally, and the incorporated fatty acid is removed by hydroxylamine treatment at pH 7 or 11 and by sulfhydryl reducing agents, suggesting a thioester linkage to palmitic acid. Consistent with this, p75LNTR in which the juxtamembrane cysteine present at position 279 is substituted with alanine is expressed but cannot be metabolically labeled with [3H]palmitic acid. Substitution of other cysteine residues present in the transmembrane or intracellular domain of the receptor has no effect on protein acylation, suggesting that only Cys279 is esterified to palmitate. PMID- 7982985 TI - Palmitoylation of luteinizing hormone/human choriogonadotropin receptors in transfected cells. Abolition of palmitoylation by mutation of Cys-621 and Cys-622 residues in the cytoplasmic tail increases ligand-induced internalization of the receptor. AB - We have examined whether the two cysteine residues (621 and 622) of the carboxyl terminal cytoplasmic domain of the rat luteinizing hormone (LH/hCG) receptor are potential sites for palmitoylation. The full-length LH/hCG receptor cDNA was cloned into an expression vector (hCGR-pCMV4). A human embryonic kidney cell line expressing large T antigen (293T cells) was transiently transfected with hCGR pCMV4 by the calcium phosphate precipitation technique. The functional expression of the receptor was confirmed by 35S-labeled cysteine incorporation into the receptor as well as by 125I-human chorionic gonadotropin (hCG) binding. The transfected cells were then labeled with [3H]palmitic acid, and the labeled receptors purified on hCG-Affi-Gel matrix and subjected to SDS-polyacrylamide gel electrophoresis and autoradiography. The hCGR-pCMV4-transfected cells incorporated [3H]palmitic acid into a 92-kDa band corresponding to the mature form of the LH/hCG receptor; this band was absent in cells transfected with vector alone. Site-directed mutagenesis of either cysteine 621 or 622 to serine residue was partially inhibitory, whereas mutation of both cysteine residues (621 and 622) completely abolished palmitoylation. Scatchard analyses revealed that the mutant and wild type receptors have similar affinities for 125I-hCG. The biological function of palmitoylation was then examined in the transfected cells. The results showed that although the intracellular trafficking of the receptor and the ability to stimulate cyclic AMP production were unaffected, the rate of ligand-induced internalization of the receptor was higher in palmitoylation deficient mutants compared to the wild type receptors. The first order rate constants of internalization of the mutant receptors were over 2-fold higher than the wild type. Intracellular degradation of the receptor-bound ligand was also higher in the mutants. These studies suggest that the native LH/hCG receptor is palmitoylated at cysteine residues 621 and 622, creating a membrane-anchoring site at the putative cytoplasmic domain. This palmitic acid-mediated anchoring decreases the ligand-induced receptor internalization thereby prolonging the retention of the ligand-bound receptor on the cell surface. PMID- 7982986 TI - Prosomatostatin processing in pituitary GH3 cells. Identification and secretion of the intact propeptide. AB - Preprosomatostatin (preproSRIF) is a peptide hormone precursor that undergoes tissue-specific processing at either a single set of paired basic residues to yield SRIF-14 or, alternatively, at a monobasic site to produce SRIF-28, an NH2 terminally extended form of SRIF-14. Mammalian preproSRIFs are a family of precursors that are remarkably conserved from rat to humans. In five species, the signal peptide and propeptides are approximately 96% identical; this high degree of sequence identity may be indicative of functional conservation. Since the propeptide is approximately five times larger than SRIF-14, we hypothesized that it would be secreted as a separate polypeptide following proSRIF proteolytic processing. To test this idea, we raised polyclonal antibodies to the entire propeptide to follow its biosynthesis and secretion. Here we demonstrate that in transfected rat anterior pituitary GH3 cells both SRIF-14 and the intact 9.5-kDa propeptide were processed coordinately from proSRIF with identical kinetics. Treatment of the cells with chloroquine, a weak base which inhibits processing to mature SRIF-14, also inhibited the appearance of the 9.5-kDa propeptide. Approximately 40% of the propeptide was targeted to the regulated secretory pathway as determined by its quantitative secretion in response to secretagogues. We also examined the secretion of the SRIF propeptide independently of SRIF-14 by expressing a truncated "propeptide" in which SRIF-14 was deleted. Significantly, the SRIF propeptide was itself efficiently transported through the secretory pathway and secreted into the culture medium. This suggests that the propeptide possesses all the topogenic information necessary for intracellular transport. The coordinate secretion of the intact propeptide with mature SRIF-14 suggests that it might function as a novel bioactive peptide. PMID- 7982987 TI - Mutational mapping of kinetic and pharmacological properties of a human cardiac cAMP phosphodiesterase. AB - We have created a series of deletion mutants of a human cardiac cAMP phosphodiesterase in order to define sequences necessary for function and to identify residues required for inhibition by cGMP and by the drugs milrinone and trequinsin. These truncated constructs were expressed in yeast cells, and their biochemical properties were analyzed. The mutations define an amino acid sequence that is essential for function. Among the active constructs, there was considerable variability in the level of expression and in the stability of the proteins, with the full-length and near full-length constructs being the least stable. There were, however, no significant changes in Km values among the active enzymes. Cation studies confirmed that Mn2+ is a more efficient cofactor than Mg2+ or Co2+. Interestingly, Mn2+ acts as a more efficient cofactor for cGMP inhibition as well. Although IC50 values for the drugs trequinsin and milrinone were not significantly altered by deletions, there was a decrease in cGMP IC50 values for the smaller constructs, indicating a role for amino acid residues outside the catalytic region in cGMP inhibition. We also demonstrate in vivo inhibition of this enzyme in yeast cells grown in the presence of pharmacological inhibitors, allowing for the selection of drug-resistant mutants. Finally, we have constructed and analyzed chimeric genes in which portions of this phosphodiesterase are replaced with homologous sequences from a closely related phosphodiesterase isozyme that is expressed in brain. Our results demonstrate that sequence variations between related isozymes account for more than just pharmacological distinctions and may reflect significant structural differences. PMID- 7982988 TI - Proteolytically active streptococcal pyrogenic exotoxin B cleaves monocytic cell urokinase receptor and releases an active fragment of the receptor from the cell surface. AB - Urokinase plasminogen activator (u-PA) receptor (u-PAR) is a glycosyl phosphatidylinositol-anchored membrane protein that promotes pericellular proteolysis and cellular migration. This investigation demonstrates that u-PAR is a substrate for the proteolytically active form of streptococcal pyrogenic exotoxin B (SPE B), a potent virulence factor secreted by Streptococcus pyogenes. Treatment of U937 monocyte-like cells with SPE B decreased specific 125I-labeled single-chain u-PA binding by up to 85%. Cysteine proteinase inhibitors neutralized SPE B without affecting the activity of phosphatidylinositol-specific phospholipase C. Due to decreased u-PA binding, SPE B-treated U937 cells expressed decreased activity against a u-PA-specific fluorogenic substrate and plasminogen. SPE B released single-chain u-PA that was noncovalently bound to U937 cells or cross-linked to cellular receptors with bis(sulfosuccinimidyl) suberate. The mass of the released u-PA-receptor complex was 100 kDa. Western blot analysis confirmed that the u-PA receptor that was cleaved by SPE B is u PAR. After deglycosylation, the mass of SPE B-released u-PAR was 35 kDa, slightly smaller than the phosphatidylinositol-specific phospholipase C-derived form of this receptor. SPE B-released u-PAR retained the ability to bind u-PA, as determined by u-PA affinity chromatography. We conclude that SPE B may inhibit u PA binding to monocytic cells by at least two mechanisms: (i) by decreasing the level of functional cell surface u-PAR and (ii) by releasing a soluble form of u PAR that competes with the cellular receptor for ligand. PMID- 7982989 TI - Role of the leucine zipper in the kinetics of DNA binding by transcription factor USF. AB - USF is a transcription factor characterized by a helix-loop-helix (HLH) DNA binding domain that has been highly conserved through evolution. Vertebrate USFs contain an additional C-terminal leucine zipper (LZ) immediately adjacent to the HLH domain. This LZ is essential for efficient DNA binding by human USF. However, sea urchin has a USF family member that lacks a LZ and yet binds DNA efficiently. To clarify the role of the LZ in DNA binding by USF, we compared the properties of human and sea urchin USFs and found that the two proteins interacted with their specific sites on the DNA with identical affinities but very different kinetics. Association and dissociation rate constants of sea urchin USF were about 10-fold those of human USF. Domain-swapping experiments revealed that the LZ was responsible for the slower kinetics of human USF. USF heterodimers containing a single LZ displayed rates intermediate between those of dimers containing either two or no LZ, indicating that zipper-zipper interactions within USF dimers were not important for DNA binding. Temperature effects on DNA-binding parameters revealed a very high energy barrier for binding of human USF to DNA. Presence of a LZ increased the activation energy of the reaction. PMID- 7982990 TI - Purification to homogeneity of UDP-glucose:glycoprotein glucosyltransferase from Schizosaccharomyces pombe and apparent absence of the enzyme fro Saccharomyces cerevisiae. AB - The UDP-Glc:glycoprotein glucosyltransferase was purified to homogeneity from the fission yeast Schizosaccharomyces pombe. The enzyme has been recently suggested to be involved in the mechanism by which unfolded, partially folded, or misfolded glycoproteins are retained in the endoplasmic reticulum. The pure yeast glucosyltransferase formed protein-linked Glc1-Man9GlcNAc2,Glc1Man8GlcNAc2, and Glc1Man7GlcNAc2 when incubated with UDP-Glc and denatured thyroglobulin. The same compounds were formed upon glucosylation of endogenous acceptors by crude microsomes. The enzyme was a soluble microsomal protein that required Ca2+ for activity, used UDP-Glc and not TDP-Glc, ADP-Glc, or UDP-Gal as sugar donor, had an almost neutral optimum pH value, and as the glucosyl-transferase obtained from rat liver, glucosylated denatured but not native glycoproteins or glycopeptides. A similar enzymatic activity could not be detected in Saccharomyces cerevisiae microsomes and transient glucosylation of glycoproteins (addition of a single glucose unit to glucose-free oligosaccharides by the glucosyltransferase followed by its removal by glucosidase II) could not be detected in intact S. cerevisiae cells. These are the only eukaryotic cells described so far in which these processing reactions of the endoplasmic reticulum do not occur. Availability of the pure S. pombe enzyme will eventually allow testing the possible involvement of the glucosyltransferase in sensing glycoprotein tertiary structures in the endoplasmic reticulum. PMID- 7982991 TI - Low density lipoproteins induce parasympathetic responsiveness in embryonic chick ventricular myocytes in parallel with a coordinate increase in expression of genes coding for the M2 muscarinic receptor, G alpha i2, and the acetylcholine sensitive K+ channel. AB - Growth of chick atrial cells in medium supplemented with lipoprotein-depleted serum has been shown to result in an increase in total cell cholesterol, and an increase in the negative chronotropic response to muscarinic stimulation in parallel with an increase in levels of muscarinic receptors and the G-protein alpha-subunits alpha i and alpha o (Haigh, L. S., Leatherman, G. F., O'Hara, D. S., Smith, T. W., and Galper, J. B. (1988) J. Biol. Chem. 263, 15608-15618). In this study we determined whether growth of chick ventricular cells in medium supplemented with lipoprotein depleted serum could alter levels of muscarinic receptors and G-protein alpha-subunits and induce a negative chronotropic response to muscarinic stimulation. We further determined whether levels of mRNA coding for muscarinic receptors, G-proteins, and the acetylcholine-sensitive K+ channel were coordinately regulated. Growth of embryonic chick ventricular cells from hearts 14 days in ovo in medium supplemented with lipoprotein depleted serum resulted in a 21 +/- 5% (n = 3, +/- S.E.) increase in muscarinic receptor number as demonstrated by [3H]quinuclidinyl benzilate binding and a 4.7 +/- 1.0 (+/- S.E., n = 4)-fold increase in G alpha i2 as demonstrated by Western blot analysis. These changes in receptor and G-protein were associated with a coordinate increase in levels of mRNA coding for the M2 muscarinic receptor, G alpha i2 and the acetylcholine sensitive K+ channel as determined by RNase protection. These increases were reversed by addition of 30 microM mevinolin, an inhibitor of HMG-CoA reductase activity. Carbamylcholine (0.1 mM) had no effect on beat rate in ventricular cells grown in medium supplemented with fetal calf serum. Cells grown in medium supplemented with lipoprotein depleted serum demonstrated a 40 +/- 8% (+/- S.E., n = 10, p < 0.0001) decrease in beat rate in response to 0.1 mM carbamylcholine which was reversed by the addition of 30 microM mevinolin. These data suggest that, during growth in medium supplemented with lipoprotein depleted serum, a component of the cholesterol biosynthetic pathway plays a role in the coordinate induction of mRNAs coding for receptors, G proteins, and an effector (ion channel) that results in the induction of a parasympathetic response in the ventricular cell characteristic of the atrial phenotype. PMID- 7982992 TI - How the ribosome moves along the mRNA during protein synthesis. AB - The movement of a ribosome along the mRNA was assessed by the following experimental strategy. mRNAs were synthesized which contained a short coding sequence with at least four codons and a 32P label at one end and an oligo(C) sequence at the other end. When these mRNAs were fixed on the ribosome with tRNAs specific for the defined codons, the oligo(C) stretches were partially outside of the ribosome, whereas the labeled ends were inside the ribosome and thus protected. The overhanging oligo(C) regions were trimmed with the cytidyl specific RNase CL3 identifying the nucleotides of the mRNAs, which emerged from the ribosome. An mRNA enters the ribosome at nucleotide 18 +/- 1, when counting starts at the first nucleotide of the P-site codon, and leaves the ribosome at nucleotide -21 +/- 2. The ribosome does not move at either side upon A-site occupation but does so at both sides simultaneously upon translocation. The results further indicate that most of the mRNA stretches downstream and upstream of the coding region are not required for the translocation reaction. It is therefore likely that the tRNAs are pulling the mRNA through the ribosome via codon-anticodon interactions in the course of translocation. PMID- 7982993 TI - Thiol reducing reagents inhibit the heat shock response. Involvement of a redox mechanism in the heat shock signal transduction pathway. AB - We evaluated the effects of thiol-reducing agents on the heat shock response in human and rodent cells in culture. Using HeLa cells as an example, we demonstrated that dithiothreitol (DTT,2mM) inhibited the heat (42 degrees C) induced increase in the synthesis of heat shock proteins (HSPs), abundance of mRNA of hsp 70, hsp 70 gene promoter activity, and the heat shock factor (HSF) DNA binding activity. This effect of DTT was specific and attributable to its reducing activity; oxidized DTT was ineffective, and other thiol reducing compounds had the same effect as DTT. Time course and dose-response studies showed that DTT significantly inhibited the heat shock induction of heat shock element binding activity with no preincubation and that 0.6 and 1-2 mM DTT gave half-maximal and maximal inhibition, respectively. The effect of DTT was reversible; removal of the DTT-containing medium prior to heat shock rendered the cells fully responsive. Analysis of the effects of DTT on the regulation and function of HSF suggests that DTT blocked an early and important step in the activation process without having a direct effect on the HSF protein. Thus, DTT inhibited the heat-induced trimerization, phosphorylation, and nuclear translocation of HSF and was also effective against a number of other reagents that are known to activate HSF. On the other hand, DTT did not block the response induced by heat shock at 45 degrees C, and in vitro addition of DTT failed to modulate the DNA binding activity of activated HSF present in cell extracts, suggesting that the HSF protein itself is unlikely to be a direct target of action of DTT. These results, together with the observation that activation of HSF DNA binding activity was attenuated under an anoxic condition and that hydrogen peroxide mimicked the effects of heat shock, suggest the involvement of a redox mechanism as an early and important step in the heat shock signal transduction pathway. PMID- 7982994 TI - Triple hydroxylation of tetracenomycin A2 to tetracenomycin C in Streptomyces glaucescens. Overexpression of the tcmG gene in Streptomyces lividans and characterization of the tetracenomycin A2 oxygenase. AB - Nucleotide sequence analysis of the tcmG gene has suggested that the TcmG protein is responsible for the triple-hydroxylation of tetracenomycin (Tcm) A2 to Tcm C in Streptomyces glaucescens (Decker, H., Motamedi, H., and Hutchinson, C.R. (1993) J. Bacteriol. 175, 3876-3886). The heterologous expression of the tcmG gene in Streptomyces lividans and the purification and characterization of TcmG protein, which we have named Tcm A2 oxygenase, are described here. NH2-terminal amino acid analysis of the purified enzyme led to the revision of the translational start site of tcmG to a TTG, 33 base pairs downstream of the GTG site assigned initially on the basis of nucleotide sequence analysis. Tcm A2 oxygenase is a monomeric protein in solution and contains 1 mol of non-covalently bound FAD; the apoenzyme can be partially reconstituted in vitro by addition of FAD. Tcm A2 oxygenase exhibits an optimal pH of 9.0-9.5 and prefers NADPH over NADH as an electron donor. The apparent K'm of the enzyme for Tcm A2, NADH, and NADPH are 1.81 +/- 0.38, 260 +/- 19, and 82.1 +/- 17 microM, respectively, and the apparent V'max for the reaction is 14.7 +/- 1.1 nmol Tcm C/min.mg. Purification and characterization of Tcm A2 oxygenase provide direct evidence to support the notion that the angular hydroxy groups of naphthacenequinones like Tcm C are introduced from 18O2 via a mono- or dioxygenase process. PMID- 7982995 TI - Activation of Na+/H+ exchange by platelet-derived growth factor involves phosphatidylinositol 3'-kinase and phospholipase C gamma. AB - The effect of site-specific mutations in the mouse platelet-derived growth factor (PDGF) beta-receptor on activation of the Na+/H+ exchanger was examined in normal murine mammary gland epithelial (NMuMG) and Chinese hamster ovary (CHO) cells. These cells, which do not normally express PDGF receptors, were stably transfected with PDGF beta-receptor cDNA. Intracellular pH and Ca2+ were monitored using fluorescent probes. In both NMuMG and CHO cells expressing wild type PDGF beta-receptors, PDGF B/B activated the amiloride-sensitive Na+/H+ exchanger. In both cell types, cell alkalinization was reduced by approximately 50% with a receptor mutant Y708F,Y719F which cannot bind phosphatidylinositol (PI) 3'-kinase. An inhibitor of PI 3'-kinase, LY294002, also inhibited alkalinization by 43% in cells with wild-type, but not Y708F,Y719F receptors. PDGF-induced intracellular Ca2+ release was not affected by this mutation. Both alkalinization and Ca2+ release were reduced by nearly 100% with the mutant Y977F,Y989F, which cannot bind phospholipase C gamma (PLC gamma). Y739F, a mutant that fails to bind the GTPase-activating protein did not affect PDGF-induced alkalinization. In protein kinase C (PKC) down-regulated NMuMG cells (wild-type receptor), PDGF no longer activated the Na+/H+ exchanger. In contrast, in PKC down-regulated CHO cells (wild-type receptor), PDGF-induced alkalinization was attenuated by only 37%. This residual activity was unaffected by the Y708F,Y719F mutation, but was completely eliminated by removal of medium Ca2+. These findings indicate that phospholipase C gamma is essential for activation of Na+/H+ exchange. PI 3'-kinase participates in PKC-dependent activation of Na+/H+ exchange by PDGF. In CHO cells, there is a second, Ca(2+)-dependent mechanism for activation of the exchanger. PMID- 7982996 TI - Expression of human thymidylate synthase in Escherichia coli. PMID- 7982997 TI - Guanylyl cyclase receptors. PMID- 7982998 TI - Detergent-insoluble glycolipid microdomains in lymphocytes in the absence of caveolae. AB - Antibody binding to glycolipids and glycophosphatidylinositol (GPI)-anchored proteins of lymphocytes can trigger activation of specific signal transduction pathways. The finding that GPI-anchored proteins are present in detergent insoluble complexes with several tyrosine kinases of the Src family suggested that these complexes may represent membrane microdomains involved in the transduction of signals to the cell interior. Recent work has suggested a link between detergent-insoluble microdomains and plasma membrane invaginations termed caveolae. Here we show that lymphocytes lack plasma membrane domains with the characteristic features of caveolae. Furthermore, VIP21-caveolin was not detectable in four different lymphocyte cell lines at the protein or mRNA level. In addition to the lack of caveolar domains, capping experiments suggested that the bulk of the GPI-anchored protein Thy1 and the glycosphingolipid GM1 were not stably associated in the lymphocyte plasma membrane. Despite this, Thy1 and GM1 were present in detergent-insoluble complexes. We conclude that detergent insolubility does not correlate with the presence of caveolae or of VIP21 caveolin and that caveolae, as defined by a number of different markers, are not involved in signal transduction in lymphocytes. PMID- 7983000 TI - Distinct roles of the intracellular domains of transforming growth factor-beta type I and type II receptors in signal transduction. AB - Transforming growth factor-beta (TGF-beta) transduces signals through binding to type I (T beta R-I) and type II (T beta R-II) serine/threonine kinase receptors. T beta R-I requires T beta R-II for ligand binding, whereas T beta R-II requires T beta R-I for signaling. We generated two different chimeric TGF-beta receptors, i.e. T beta R-1.2 containing the extracellular domain of T beta R-I and the intracellular domain of T beta R-II, and T beta R-2.1 containing the extracellular domain of T beta R-II and the intracellular domain of T beta R-I. T beta R-2.1 bound 125I-TGF-beta 1 alone, whereas T beta R-1.2 bound the ligand only in the presence of T beta R-II or T beta R-2.1. When transfected into a mutant mink lung epithelial cell line that lacks functional T beta R-II, T beta R II cDNA, but not T beta R-2.1 cDNA, restored the responsiveness to TGF-beta 1 with regard to transcriptional activation of plasminogen activator inhibitor-1 gene promoter and 12-O-tetradecanoylphorbol-13-acetate-responsive elements. In a mutant mink lung epithelial cell line lacking T beta R-I, T beta R-I cDNA stimulated promoter activity, but the T beta R-1.2 cDNA did not. T beta R-2.1 formed an oligomer with T beta R-II when transfected into COS cells, but the complex did not transduce the signal after ligand stimulation. On the other hand, co-transfection of T beta R-1.2 and T beta R-2.1 cDNAs restored the responsiveness to TGF-beta 1. These results indicate that an interaction between the intracellular regions of T beta R-I and T beta R-II, triggered by ligand binding to the extracellular domains of these receptors, leads to efficient signal transduction by TGF-beta. PMID- 7982999 TI - Rac translocates independently of the neutrophil NADPH oxidase components p47phox and p67phox. Evidence for its interaction with flavocytochrome b558. AB - When the neutrophil NADPH oxidase is activated to generate superoxide, the cytosolic components, p47phox, p67phox, and the GTP-binding protein Rac, become stably associated with the plasma membrane. The translocation of p47phox and p67phox is dependent on the presence in the membrane of the flavocytochrome b558, itself composed of two subunits, gp91phox and p22phox. In this study we have quantitated Rac1 and Rac2 in human neutrophils and show that > 96% of the Rac protein is Rac2 and that chronic granulomatous disease (CGD) neutrophils contain normal levels of the protein. We used a cell-free translocation system as well as intact normal and CGD neutrophils to determine whether the translocation of Rac2 is dependent upon the presence of the other oxidase components. When cell-free reactions contained any combination of normal, p47phox-deficient or p67phox deficient cytosol and normal or flavocytochrome b558-deficient membranes, the GTP gamma S (guanosine 5'-3-O-(thio)triphosphate)-dependent association of Rac2 with the re-isolated membranes was not significantly different from the control mixture of normal membranes and cytosol. In intact CGD neutrophils lacking p47phox or p67phox and stimulated with phorbol myristate acetate the translocation of Rac2 was also normal, and we conclude that Rac translocation can occur independently of the cytosolic NADPH oxidase components. In contrast, in the absence of flavocytochrome b558 from intact X-chromosome linked CGD neutrophils, Rac2 translocation was reduced to only 25% of the control value. On the basis of these observations we propose that while Rac2 can bind to a site distinct from either gp91phox or p22phox, it depends upon an interaction with the flavocytochrome b558 for maximal stability in the membrane. PMID- 7983001 TI - Specific cleavage of the 70-kDa protein component of the U1 small nuclear ribonucleoprotein is a characteristic biochemical feature of apoptotic cell death. AB - The U1 small nuclear ribonucleoprotein particle is essential for splicing of precursor mRNA, an activity that depends upon both the RNA and protein components of the U1 particle. One of the U1-specific proteins that is functionally important in this splicing reaction is the 70-kDa protein (U1-70kDa). We report here that U1-70kDa is specifically cleaved in apoptotic cells, resulting in the generation of a 40-kDa fragment. The kinetics of this cleavage coincided with the appearance of cells with apoptotic morphology in the population, and the proportion of 40-kDa fragment observed was markedly increased in apoptotic cells that had become detached from the substratum. Although the inhibitor characteristics of the activity cleaving U1-70kDa suggest that interleukin 1 beta converting enzyme (ICE) might be responsible, the specific ICE inhibitor N-(N acetyl-tyrosinyl-valinyl-alaninyl)-3-amino-4-oxob utanoic acid (YVAD-CHO) did not prevent cleavage, and U1-70kDa was not cleaved by purified ICE in vitro. Further study of this novel cleavage and the enzyme responsible will yield information about proteolytic events that might be central in the mechanism and control of apoptosis. PMID- 7983002 TI - CPP32, a novel human apoptotic protein with homology to Caenorhabditis elegans cell death protein Ced-3 and mammalian interleukin-1 beta-converting enzyme. AB - We have cloned a novel apoptotic gene from human Jurkat T-lymphocytes. The new gene encodes a 32-kDa putative cysteine protease (CPP32) with significant homology to Caenorhabditis elegans cell death protein Ced-3, mammalian interleukin-1 beta-converting enzyme (ICE), and the product of the mouse nedd2 gene. The CPP32 transcript is highly expressed and most abundant in cell lines of lymphocytic origin. Overexpression of CPP32 or ICE in Sf9 insect cells resulted in apoptosis. In addition, coexpression of recombinant p20 and p11 derived from the parental full-length CPP32 sequence resulted in apoptosis in Sf9 cells. Our data suggest that similar to ICE, CPP32 is made of two subunits, p20 and p11, which form the active CPP32 complex. The apoptotic activity of CPP32 and its high expression in lymphocytes suggest that CPP32 is an important mediator of apoptosis in the immune system. PMID- 7983003 TI - Fibronectin attachment activates the NF-kappa B p50/p65 heterodimer in fibroblasts and smooth muscle cells. AB - The nuclear factor kappa B, NF-kappa B, is activated by numerous inflammatory mediators, regulating biological responses that in part are dependent on the extracellular matrix. Analyses of the influence of cell-matrix interaction on NF kappa B activation revealed that attachment to fibronectin caused an increase in NF-kappa B activity corresponding to 3-fold the level in cells plated on bare plastic. This effect was dependent on the degree of attachment and appeared to involve both the RGD motif of the cell-binding domain, and the heparin-binding domain of fibronectin. Fibronectin attachment specifically caused activation of the p50/p65 heterodimeric form of NF-kappa B, resulting in an increase of this complex to a level similar to that induced by cytokine stimulation. These data show that cell attachment has a pronounced influence on the level of NF-kappa B activity, affecting specific dimeric complexes, and suggest this to be a pathway through which effects depending on cell-matrix interaction can regulate cell behavior and cytokine responses. PMID- 7983004 TI - Insulin-inducible changes in insulin receptor mRNA splice variants. AB - Alternative splicing of insulin receptor pre-mRNA has been shown to be regulated in a tissue-specific and developmental manner. We investigated whether the receptor ligand might regulate the relative distribution of alternatively spliced mRNA in insulin-sensitive cells and found that changes in the relative expression of the two alternatively spliced insulin receptor RNA isotypes expressed in hepatocytes are regulated by insulin. In addition, we observed significant differences (p < or = 0.001) in insulin receptor isotype expression in subjects who were hyperinsulinemic and insulin-resistant versus subjects who were insulin sensitive. These results support a role for insulin in the regulation of the relative expression of alternatively spliced mRNA expressed in insulin-responsive cells and tissues. PMID- 7983005 TI - The Alzheimer A beta peptide develops protease resistance in association with its polymerization into fibrils. AB - An intriguing property of the polypeptide constituents of amyloid is that they apparently can escape the proteolytic mechanisms that normally catalyze turnover and prevent abnormal tissue accumulation of polypeptides. Here, we demonstrate that the A beta peptide, the principal component of cerebrovascular amyloid deposits in Alzheimer's disease, becomes resistant to an array of proteases as a result of structural changes associated with its polymerization into amyloid fibrils. It is further demonstrated that fibril formation per se does not lead to protease resistance but probably structural changes associated with polymerization. The results suggest that higher order structural changes, regulated by the primary structure, enable amyloidogenic polypeptides to escape proteolytic degradation and accumulate in tissues. PMID- 7983006 TI - The major protein of GLUT4-containing vesicles, gp160, has aminopeptidase activity. AB - A glycoprotein of M(r) 160,000 (gp160) represents the major protein component of GLUT4-containing vesicles other than GLUT4 itself. These vesicles are the tissue specific secretory-like microsomal structures that are responsible for insulin dependent translocation of GLUT4 to the cell surface in fat and muscle cells. Our previous studies demonstrated that the expression of gp160 is also limited to fat and muscle tissues, where it is localized exclusively in GLUT4-containing vesicles, and thus, it represents a marker protein for insulin-activated glucose transport. We demonstrate here that gp160 has structural homology to aminopeptidase N and possesses aminopeptidase activity in vitro. Since aminopeptidase activity has also been found in a variety of secretory type vesicles from other tissues, it may be essential for the organization and functioning of secretory machinery in different cell types. PMID- 7983007 TI - Absolute requirement of cyclic nucleotide in the activation of the G141Q mutant cAMP receptor protein from Escherichia coli. AB - cAMP receptor protein (CRP), when interacting with cAMP, controls the expression of a network of catabolite-sensitive genes in Escherichia coli. To understand the molecular events that lead to the activation of CRP, a combined approach of site directed mutagenesis and thermodynamic analysis was employed to study a member of a specific class of CRP mutant, CRP, which activates the in vivo expression of CRP-dependent operons in cya- strains in the absence of exogenous cAMP. Results from in vitro studies show that the CRP mutant G141Q absolutely requires cAMP for interacting with specific DNA. A quantitative comparison of the thermodynamic parameters governing ligand binding and DNA-protein complex formation in the presence of different cyclic nucleotides leads to the conclusion that this CRP mutant is activated only in the presence of cyclic nucleotides. The specificity toward cyclic nucleotides exhibited by wild-type CRP is lost in this mutant. Furthermore, the binding affinity of the ligand for the first binding site of the mutant is essentially the same as that of wild-type CRP regardless of the identity of the cyclic nucleotide. Hence, the observed in vivo activation of CRP dependent operons by G141Q in the absence of exogenous cAMP is most likely the consequence of the replacement of cAMP by other cyclic nucleotides to activate the mutant. It is also possible that trace levels of cAMP present in the cya- strain could account for the in vivo activation of the mutant. Furthermore, these results indicate that this CRP mutant does not assume the activated conformation in the absence of cyclic nucleotides, in contrast to the current model derived from results of in vivo studies. PMID- 7983008 TI - Identification of discrete segments of human Raf-1 kinase critical for high affinity binding to Ha-Ras. AB - A critical event in a signal transduction pathway downstream of receptor tyrosine kinases is the physical association of GTP-liganded Ras with the serine/threonine kinase, Raf-1. The binding of Raf-1 to Ras results in translocation of the kinase to the plasma membrane and facilitates its activation by an unknown mechanism. A deletion mutagenesis approach was employed to elucidate critical sequences in Raf 1 necessary for binding to Ras and to resolve seemingly contradictory data in the literature. While an N-terminal fragment consisting of residues 2-130 of Raf-1 was able to bind Ras, residues 131-147 were found to be critically important for conferring high affinity binding to Ras. Surprisingly, a second domain between residues 52-64 was an essential element for Raf-Ras interaction, although it did not appear to form an independent binding site for Ras. These findings may prove useful for the design of peptides or peptidomimetic drugs for the modulation of Raf-Ras interaction in neoplastic disorders. PMID- 7983010 TI - Structure and expression of the potato ADP-glucose pyrophosphorylase small subunit. AB - ADP-glucose pyrophosphorylase (AGP) catalyzes a key regulatory step in starch synthesis. To elucidate the molecular basis for the expression of the potato (Solanum tuberosum L.) AGP during tuber development, the structure of the small subunit AGP (sAGP) gene and its patterns of expression were examined. DNA sequence analysis revealed that the sAGP gene is over 5.5 kilobases long and has a complex structure including eight introns. Unlike the situation in other plants where tissue-specific sAGP are found, our Southern and Northern blot analysis indicated that the same sAGP gene is expressed both in tubers (non-photosynthetic tissue) and leaves (photosynthetic tissue). These data were supported by comparing sequences of isolated sAGP leaf cDNAs to the tuber cDNA sequence, by primer extension analysis of leaf and tuber poly(A)+ RNAs, and by the spatial expression patterns of a gusA (beta-glucuronidase) reporter gene driven by the potato sAGP promoter in transgenic potato plants. Although the sAGP gene appeared to be transcriptionally controlled in both developing tubers and in leaves, the relative level of leaf antigen was significantly lower than its level of transcript, indicating that sAGP expression in leaves is primarily regulated post transcriptionally. The observed tissue type-dependent regulation of sAGP expression appears to control the extent of starch biosynthesis by regulating the levels of this enzyme and, thus, alleviate the need for tissue-specific forms of the sAGP in potato. PMID- 7983009 TI - A single promoter directs both housekeeping and erythroid preferential expression of the human ferrochelatase gene. AB - We have isolated and characterized the 5'-flanking region of the gene for human ferrochelatase (HFC), the last enzyme of the heme biosynthetic pathway. The proximal promoter of the gene is contained within a region that structurally resembles a CpG island and is devoid of general cis elements such as TATA and CAAT boxes. Recognition sites for the ubiquitous Sp1 family of transcription factors, as well as for the erythroid-specific trans-acting factors NF-E2 and GATA-1 were found, and binding of regulatory proteins to these elements was analyzed by in vitro DNase I protection assays. The contribution of the various cis elements to both ubiquitous and erythroid preferential expression of the HFC gene was assessed by using transient transfection assays. These showed that a minimal Sp1-driven promoter devoid of the upstream erythroid-specific elements was sufficient for erythroid preferential expression of the HFC gene. However, elimination of a repressor sequence lying between the minimal promoter and the erythroid-specific elements resulted in high levels of expression in human erythroleukemic K562 cells only when the cis elements recognized by GATA-1 and NF E2 were present, suggesting that the activity of these factors is regulated by a downstream repressor in erythroid cells. PMID- 7983011 TI - Identification, molecular cloning, and characterization of dual leucine zipper bearing kinase. A novel serine/threonine protein kinase that defines a second subfamily of mixed lineage kinases. AB - Molecular cloning using a degenerate oligonucleotide-based polymerase chain reaction was undertaken to test the possibility that novel, developmentally regulated protein kinases are expressed in the embryonic mouse kidney. Several receptor tyrosine kinase and serine/threonine kinase cDNA clones were identified. One of these, designated DLK, represented a novel gene product whose 3.6-kilobase transcript was expressed in a tissue-specific and developmentally regulated fashion. Several clones encoding the entire open reading frame were isolated and sequenced. The identified open reading frame encodes an 888-amino acid polypeptide that defines a new subfamily within the mixed lineage protein kinase family. Sequence analysis revealed: 1) a kinase catalytic domain most characteristic of serine/threonine kinases but hybrid between members of the family of microtubule-associated protein kinase kinase kinases and the fibroblast growth factor receptor family; 2) two putative alpha-helical leucine zipper motifs separated by a 25-amino acid charged intermediate segment but lacking an NH2-terminal basic domain; and 3) COOH-terminal and NH2-terminal proline-rich domains suggestive of src homology 3 (SH3) domain binding regions. Rabbit polyclonal immune sera generated against a carboxyl-terminal bacterial fusion protein recognized a protein with an apparent molecular mass of 130 kDa in COS 7 cells that were transiently transfected with a full-length DLK cDNA expression vector. Moreover, COS 7 cells transiently transfected with an epitope-tagged DLK expression vector expressed protein with an apparent molecular mass of 130 kDa that became autophosphorylated on serine and threonine in an in vitro kinase assay. PMID- 7983012 TI - Two types of proton-modulated calcium binding in the sarcoplasmic reticulum Ca(2+)-ATPase. I. A model of two different conformations of chemically equivalent ATPase molecules. AB - Two pools of calcium binding sites of the sarcoplasmic reticulum Ca(2+)-ATPase have been found at 0 degrees C: Half of the calcium sites are in a slow (t1/2 > or = 2 s)/rapid (t1/2 < 2 s) binding site dependent on pH, and the other half are in a slow binding state independent of pH (Nakamura, J. (1989) J. Biol. Chem. 264, 17029-17031). Herein, to clarify the molecular basis of the two calcium sites, the relation between calcium binding to the enzyme and phosphorylation of the enzyme was examined at pH 7.40, where the calcium sites are split into rapid and slow binding states. The enzyme was slowly or rapidly phosphorylated with ATP, accompanied by slow or rapid calcium binding with a stoichiometry of about 1:2. Analysis of the amino acid sequence of lysyl endopeptidase peptides of the ATPase preparation confirmed the homogeneity of the preparation, which was of fast twitch muscle type. These results suggest that each of the two pools of calcium sites belongs to one of the two different conformations of chemically equivalent ATPase molecules, which are in pH-dependent equilibrium between E1 (high affinity state for calcium) and E2 (low affinity state for calcium) and predominantly in E2 independent of pH, respectively, before calcium binding. PMID- 7983013 TI - Two types of proton-modulated calcium binding in the sarcoplasmic reticulum Ca(2+)-ATPase. II. Characteristics of their calcium bindings. AB - The first part of this study reported the existence of two different conformations of chemically equivalent Ca(2+)-ATPase molecules from the sarcoplasmic reticulum, which were in pH-dependent equilibrium between E1 (high affinity state for calcium) and E2 (low affinity state for calcium) and predominantly in E2 independent of pH, respectively, before calcium binding (Nakamura, J., and Furokohri, T. (1994) J. Biol. Chem, 269, 30818-30821). Here, calcium bindings at the ATPase molecules were further studied by varying [Ca2+] and pH at 0 degree C. The molecule, which pre-existed in equilibrium between E1 and E2, noncooperatively (the Hill value (nH) approximately 1) bound calcium with an apparent calcium affinity (K0.5) of 2-6 microM independent of pH. nH of the pH profile of the pre-existing equilibrium was about 2, suggesting participation of two protons in the equilibrium. On the other hand, the molecule, which predominantly pre-existed in E2, cooperatively (nH approximately 2) bound calcium with K0.5, which was increased from about 7 microM to about 0.2 microM by increasing pH from 6.23 to 7.40. Analysis of pH dependency of the K0.5 showed participation of 1 proton/calcium in competition for the binding sites. Calcium bindings at the two ATPase molecules seem to be differently modulated by the proton(s). PMID- 7983014 TI - Glucocorticoids and insulin regulate expression of the human gene for insulin like growth factor-binding protein-1 through proximal promoter elements. AB - Glucocorticoids stimulate, while insulin inhibits, the hepatic transcription of insulin-like growth factor-binding protein-1 (IGFBP-1). In the present studies, human HEP G2 hepatoma cells were transiently transfected with human (h)IGFBP-1 promoter constructs. Activity of a construct containing the first 1205 base pairs (bp) of the hIGFBP-1 promoter was stimulated 6-9.5-fold by dexamethasone, and this increase was inhibited approximately 76% by insulin. Deletion and site directed mutations of the hIGFBP-1 promoter (a) identified two glucocorticoid response elements, located within the first 200 bp of the promoter, which are essential for dexamethasone-stimulated promoter activity and which specifically bind human glucocorticoid receptor; (b) showed that a recently characterized insulin-responsive element, located approximately 110 bp 5' to the transcription start site (Suwanichkul, A., Morris, S.L., and Powell, D. R. (1993) J. Biol. Chem. 268, 17063-17068), confers the entire inhibitory effect of insulin not only on basal but also on glucocorticoid-stimulated promoter activity; and (c) showed that this insulin-responsive element is essential for maximal glucocorticoid stimulated activity. These studies suggest that the interaction of proteins that bind to a cluster of cis elements located in the first 200 bp of the hIGFBP-1 promoter are of major importance in modulating the opposing effects of glucocorticoids and insulin on hepatic hIGFBP-1 expression. PMID- 7983015 TI - Activation of dynamin GTPase is a result of positive cooperativity. AB - Dynamin is a GTP-binding protein thought to be involved in the early stages of endocytosis. Presently, it is not known how dynamin GTP binding and hydrolysis are related to its role in this process. We previously characterized the ability of acidic phospholipid vesicles and microtubules to strongly stimulate the GTPase activity of purified brain dynamin. In a further analysis of dynamin enzymatic properties, we have found that the increase of dynamin GTP hydrolysis in the presence of activating agent depends on enzyme concentration. At low enzyme concentration, little or no activation is observed. Plots of dynamin GTPase activity with increasing enzyme concentration in the presence of either activating agent are strongly sigmoidal, indicating that positive cooperativity is responsible for the increased activity observed. A Hill coefficient of 2.3 was determined, implying that at least two dynamin molecules associate for maximal GTPase activity. No cooperative effects in GTP binding were observed. Linear transformation of reaction velocity versus enzyme concentration data indicate an apparent Km for dynamin-dynamin interactions of 37 nM, which is significantly lower than the physiological concentration of dynamin in brain. These results suggest that cooperative interactions between dynamin molecules are responsible for the apparent activation of GTPase observed and are likely involved in dynamin function in vivo. PMID- 7983016 TI - Transcription factor egr-1 is involved in phorbol 12-myristate 13-acetate-induced megakaryocytic differentiation of K562 cells. AB - Transcription factors play important roles in regulating cell growth and differentiation. egr-1, a transcription factor of the zinc finger family, is rapidly activated in many types of cells after mitogen treatment. In this report, we demonstrate that egr-1 mRNA expression, detected by Northern blotting, is activated within 30 min of treatment of the erythroleukemia cell line K562 with phorbol 12-myristate 13-acetate (PMA), and the increased egr-1 mRNA level is associated with an elevated egr-1 antigen expression detected by Western blotting and with its DNA binding activity shown by the gel mobility shift assay. In addition, PMA-mediated activation of egr-1 mRNA expression involves no new protein synthesis and is followed by sequential down-regulation of the mRNA level of GATA-1 and glycophorin A. On the other hand, CD41a surface antigen expression is dramatically up-regulated. Furthermore, enforced expression of egr-1, through transfection of K562 cells with the egr-1 expression plasmid construct, results in expression of the egr-1 transcript that accompanies a significant accumulation on the cell surface of CD41a but not CD14 nor glycophorin A. These observations suggest that egr-1 is involved in regulating PMA-induced megakaryocytic differentiation of K562 cell line. PMID- 7983017 TI - Thyrotropin-releasing hormone activates Ca2+ efflux. Evidence suggesting that a plasma membrane Ca2+ pump is an effector for a G-protein-coupled Ca(2+) mobilizing receptor. AB - These studies characterize the mechanisms involved in terminating the initial Ca2+ transient stimulated by thyrotropin-releasing hormone (TRH). When TRH was added to GH3 pituitary cells that had been treated with thapsigargin to block any agonist-stimulated increase in [Ca2+]i, TRH caused a decrease in [Ca2+]i. The Ca2+ clearing response was seen in pituitary GH3 cells and in nonexcitable HEK 293 cells transfected with TRH receptor cDNA, was evident at basal or elevated [Ca2+]i, and was mediated by the TRH receptor. The Ca2+ clearing response to TRH was not prevented by thapsigargin, Ca2+ ionophores, nimodipine, or replacement of extracellular Na+ but was inhibited by La3+. La3+ also increased the duration of the TRH-evoked [Ca2+]i transient. TRH-stimulated Ca2+ extrusion was directly demonstrated using extracellular fluo-3 free acid. TRH produced a 5-20-fold increase in Ca2+ efflux that was independent of extracellular Na+ and inhibited by vanadate. TRH stimulation of Ca2+ efflux was not reproduced by phorbol esters or inhibited by down-regulation of protein kinase C or staurosporine. The results suggest that agonist-activated Ca2+ efflux may be a universal component of an agonist-activated Ca2+ response and further suggest that a plasma membrane Ca2+ pump may be an effector for G-protein-coupled receptors linked to Ca2+ mobilization. PMID- 7983018 TI - Molecular structure of redox metal centers of the cytochrome bo complex from Escherichia coli. Spectroscopic characterizations of the subunit I histidine mutant oxidases. AB - A site-directed mutagenesis study on the conserved subunit I histidines of the cytochrome bo complex in Escherichia coli identified ligands of the low spin heme B and CuB centers; however, the assignment of the proximal ligand of the high spin heme O was ambiguous (Minagawa, J., Mogi, T., Gennis, R. B., and Anraku, Y. (1992) J. Biol. Chem. 267, 2096-2104). We have extended this work and characterized the metal centers in the purified histidine mutant oxidases by optical, EPR, and resonance Raman spectroscopies and by biochemical analysis. We found that the H284A and H333A oxidases contain two heme B molecules, which exhibit the gz = 2.99 low spin and cyanide-sensitive g perpendicular = 6 high spin EPR signals, whereas the H419A oxidase contains only low spin heme B, which shows the gz component in a considerably higher magnetic field at g = 2.92. The CuB center was partially retained in the H284A oxidase but was almost completely lost in the H333A and H419A oxidases. Thus, we concluded that His419 is the proximal ligand of the high spin heme O and that His284 is located at the distal side of the high spin heme O. His284 plays an indispensable role in maintaining the structure of the Feo-CuB binuclear site suitable for the exogenous ligand bindings in the reduced state, since its substitution eliminated the CO binding activity. In addition, we found that His106 and His421 are in fact the axial ligands of the low spin heme B, although the H421A mutation perturbed the binuclear metal center seriously. Based upon experimental results with isotopic substitutions on iron in the oxidases, we assigned the Raman band at 208 cm-1 to the iron-histidine stretching mode (vFc(2+)-N(His)) of the wild-type ferrous cytochrome o, which was upshifted slightly by a loss of the CuB center in the H333A oxidase. A molecular structure of the metal centers and a possible mechanism of the electron transfer-coupled proton pumping in the cytochrome bo complex are proposed on the basis of our present findings. PMID- 7983019 TI - The reaction of trimethylamine dehydrogenase with diethylmethylamine. AB - The reductive half-reaction of trimethylamine dehydrogenase has been studied using the substrate diethylmethylamine over the pH range 6-10. It is found that the reaction occurs with three distinct and, under most conditions, fully resolved kinetic phases. The hyperbolic substrate concentration dependence of the observed rate constant for the fast kinetic phase is consistent with a two-step scheme in which free enzyme and substrate are in rapid equilibrium with an enzyme substrate Michaelis complex, which then reacts to produce reduced flavin. The pH dependence of the limiting rate constant for the fast phase of the reaction (klim) exhibits a pKa value of 7.9, whereas klim/Kd exhibits a pKa value of 8.7. The rate constant for the intermediate kinetic phase, which reflects intramolecular electron transfer, is controlled by an ionizable group exhibiting a pKa value of 7.3. The equilibrium distribution of reducing equivalents between the flavin and iron-sulfur center of the enzyme at the end of the intermediate phase is controlled by a different ionizable group exhibiting a pKa value of approximately 6. An overall reductive half-reaction kinetic mechanism is proposed involving formation and decay of a covalent substrate-flavin intermediate, with intrinsically rapid intramolecular electron transfer limited by the rate of decay of the covalent adduct. Under conditions of excess substrate, product release is followed by binding of a second substrate molecule, which results in full development of the spectral properties diagnostic of the spin-interacting state. PMID- 7983020 TI - Fatty acyl transfer by human N-myristyl transferase is dependent upon conserved cysteine and histidine residues. AB - N-Myristyl transferase (Nmt) catalyzes attachment of myristate onto the N terminus of suitable proteins. In order to identify amino acids important for catalytic functions, human Nmt and mutants representing all six conserved cysteine and histidine residues (Cys-169, Cys-214, His-131, His-171, His-218, and His-293) were expressed in Escherichia coli and analyzed for their ability to bind and transfer myristic acid. N-Terminal histidine-tagged fusion proteins displayed varying abilities to form an association with radiolabeled myristic acid indicative of an acyl-enzyme intermediate. When co-expressed with an acceptor substrate protein, pp60v-src, the mutants showed differential incorporation of radiolabeled myristic acid into v-Src protein. In vitro experiments monitoring transfer of myristyl CoA to a peptide homologous to the N terminus of pp60 v-src gave results similar to those obtained in vivo. Our studies showed that mutation at Cys-169, His-171, and especially His-293 interfered with formation of an acyl-enzyme intermediate, while human Nmts containing mutations at Cys-169, His-218, or His-293 showed greatly attenuated abilities to form acylated product. We propose a model for the Nmt reaction mechanism in which Cys-169 serves as the fatty acid attachment site for a covalent myristyl enzyme intermediate, while His-171 acts as a general acid/base and His-293 as a specific acid/base during acyl-enzyme intermediate formation. His-218 could then act as an acid or base needed to catalyze transfer of the acyl group from the acyl-enzyme intermediate to a polypeptide substrate. This working model will be useful for the design of regulators of Nmt function. PMID- 7983021 TI - Recognition of mitochondria-targeting signals by a cytosolic import stimulation factor, MSF. AB - MSF, a mitochondrial import stimulation factor purified from rat liver cytosol, is an ATP-dependent precursor protein conformational modulator. As a step toward understanding the specificity of substrate recognition by MSF, various synthetic peptides were examined for their ability to induce MSF ATPase activity. The peptides corresponding to various mitochondria-targeting signal sequences elicited significant ATPase activity. MSF bound the synthetic mitochondrial signal peptides, and ATP hydrolysis caused dissociation of the peptides from MSF. Basic amino acid residues in the signal peptides seemed to be essential for recognition. Thus, MSF is a member of the polypeptide chain-binding protein family with unique recognition specificity and is distinct from the hsp70 family of proteins. PMID- 7983022 TI - Palmitoylation of a G protein alpha i subunit requires membrane localization not myristoylation. AB - Palmitoylation is a dynamic, post-translational modification of the amino terminus of heterotrimeric G protein alpha subunits. Since myristoylation, beta gamma interactions, and membrane attachment also involve the amino terminus of the G protein alpha i1 subunit, we studied the relationships between palmitoylation and these events. Using COS cell transfection, the turnover of palmitate was slower on alpha i1 subunits co-expressed with beta and gamma subunits than on the alpha i1 subunit expressed alone. Mutation of cysteine 3 of alpha i1 prevented [2H]palmitate but not [3H]myristate incorporation and decreased the membrane localization of this protein. This nonpalmitoylated mutant could form a heterotrimer with co-expressed beta gamma subunits which restored its membrane localization. A nonmyristoylated alpha i1 mutant (glycine 2 to alanine) could incorporate [3H]palmitate when co-expressed with beta gamma subunits and localized to the membrane. The [3H]palmitate turnover of this nonmyristoylated mutant was more rapid than seen with the wild-type alpha i1 subunit. While myristoylation is not required for palmitoylation, both myristoylation and beta gamma association can slow the turnover of palmitate on alpha i1. These results suggest that palmitoylation maintains the membrane attachment of the free alpha subunit and changes in beta gamma association could modulate palmitoylation during signaling. PMID- 7983023 TI - Molecular characterization of a second iron-responsive element binding protein, iron regulatory protein 2. Structure, function, and post-translational regulation. AB - Several genes critical to the uptake, sequestration, and utilization of iron are regulated at the post-transcriptional level. The mRNAs encoded by these genes contain highly conserved stem-loop structures called iron-responsive elements (IREs). IREs function as the nucleic acid-binding sites for a cytosolic RNA binding protein called the IRE-binding protein or IRE-BP. Binding of the IRE-BP to IREs is reversibly regulated by the iron status of the cell. The IRE-BP is highly conserved among human, rat, mouse, and rabbit, and it is identical to the cytosolic form of aconitase. In this study, we demonstrate that a distinct human gene encoding a protein which is 57% identical to the initially described IRE-BP, now referred to as iron regulatory protein 1 or IRP1, is also capable of binding to IREs with the same in vitro affinity and specificity the originally identified protein. This second gene product, which we call IRP2, is expressed in many tissues, but its mRNA abundance and tissue distribution are different from IRP1. In most cell lines tested, levels of IRP2 are inversely regulated by iron levels due to iron-dependent regulation of the half-life of the protein. In addition to changes in total amounts of IRP2, we demonstrate that the IRE binding activity of IRP2 can also vary up to 4-fold in the absence of any change in IRP2 protein levels. The possible reasons for the existence of a second IRP are discussed. PMID- 7983024 TI - Platelet-derived growth factor stimulates growth factor receptor binding protein 2 association with Shc in vascular smooth muscle cells. AB - Platelet-derived growth factor (PDGF) stimulates smooth muscle cell proliferation and migration in vascular disorders such as atherosclerosis and restenosis. Growth factor receptor binding protein-2 (GRB2) and Shc have been shown to link growth factor receptor activation with guanine nucleotide exchange on p21-ras. We have examined this pathway in cultures of rat A10 vascular smooth muscle cells. Our data demonstrate that PDGF stimulates tyrosine phosphorylation on Shc in a concentration- and time-dependent manner that parallels PDGF beta-receptor activation. Immunoprecipitates of Shc from cells exposed to PDGF revealed Shc.GRB2 complexes. Shc immune complexes also contained PDGF beta-receptors. Complex formation was maximal with 30 ng/ml PDGF and peaked within 10 min of exposure. Although PDGF beta-receptors contain a putative GRB2 binding site, activated receptors failed to bind GRB2 directly. Evaluation of Shc from membrane and cytosolic fractions of A10 cells showed little redistribution of Shc following PDGF exposure. Cytosolic Shc bound only GRB2, whereas, membrane associated Shc complexed with GRB2, the PDGF beta-receptor, Src, and additional tyrosine phosphorylated proteins. We conclude that Shc serves as a primary docking protein for GRB2 in smooth muscle cells and is critical for proliferation in response to PDGF. PMID- 7983025 TI - Amino acid sequence of the winged bean (Psophocarpus tetragonolobus) basic lectin. Adenine binding and identification of the active-site tryptophan residue. AB - The complete amino acid sequence of winged bean basic agglutinin (WBA I) was obtained by a combination of manual and gas-phase sequencing methods. Peptide fragments for sequence analyses were obtained by enzymatic cleavages using trypsin and Staphylococcus aureus V8 endoproteinase and by chemical cleavages using iodosobenzoic acid, hydroxylamine, and formic acid. COOH-terminal sequence analysis of WBA I and other peptides was performed using carboxypeptidase Y. The primary structure of WBA I was homologous to those of other legume lectins and more so to Erythrina corallodendron. Interestingly, the sequence shows remarkable identities in the regions involved in the association of the two monomers of E. corallodendron lectin. Other conserved regions are the double metal-binding site and residues contributing to the formation of the hydrophobic cavity and the carbohydrate-binding site. Chemical modification studies both in the presence and absence of N-acetylgalactosamine together with sequence analyses of tryptophan containing tryptic peptides demonstrate that tryptophan 133 is involved in the binding of carbohydrate ligands by the lectin. The location of tryptophan 133 at the active center of WBA I for the first time subserves to explain a role for one of the most conserved residues in legume lectins. PMID- 7983026 TI - Calcium-dependent fusion among endosomes. AB - Fusion among endosomes is an important step for transport and sorting of internalized macromolecules. Working in a cell-free system, we have previously reported that, in the absence of externally added calcium, endosome fusion requires cytosol, ATP, and is sensitive to N-ethylmaleimide (NEM) and to anti-NEM sensitive factor (NSF) antibody. This cytosol-dependent fusion is regulated by monomeric and heterotrimeric GTP-binding proteins. Further studies have revealed, however, that in the presence of micromolar concentrations of free calcium, fusion is observed even in the absence of cytosol and ATP. At the electron microscope level, Ca(2+)-dependent endosome aggregation and fusion were similar to that observed for cytosol-dependent fusion. Calcium-dependent fusion was not affected by non-hydrolyzable analogs of GTP or GDP nor by NEM or anti-NSF antibody. However, Ca(2+)-dependent fusion was abrogated by trypsin treatment of the vesicles or by a membrane wash with 60 mM EDTA indicating that peripheral proteins are required. An anti-annexin II antibody and an annexin II peptide blocked Ca(2+)-dependent fusion by 50%. After the EDTA wash, Ca(2+)-dependent fusion was reconstituted by addition of purified annexin II and arachidonic acid. We conclude that endosomes can fuse by two mechanisms, one that has an absolute requirement for calcium and is probably mediated by annexins, and another that does not require calcium. PMID- 7983027 TI - Delineation of amino acid residues within hTSHr 256-275 that participate in hormone binding. AB - The amino acid sequence 256-275 of the human thyrotropin (TSH) receptor extracellular domain has previously been shown to participate in a high affinity TSH binding site by a synthetic peptide approach as well as by site-directed mutagenesis. To further investigate this binding site, we synthesized a series of peptides with alanine substitutions for each residue in the native sequence. Peptides were also synthesized containing truncations or deletions of the native sequence. Each peptide was tested for its ability to inhibit 125I-bTSH binding to porcine thyroid membrane preparations, and the concentration at which 50% inhibition of binding occurred was determined (EC50). Alanine substitution at residues Tyr258, Cys262, Cys263, Phe265, Lys266, Asn267, Lys269, Lys270, and Arg272 all resulted in statistically significant decreases in activity when compared to the native sequence (p < 0.05). Alanine substitution of the remaining residues did not alter their activity. Comparison of this sequence with the corresponding sequences of the remaining glycoprotein hormone receptors (human lutropin and human follitropin receptors) reveals that these residues lie within one of the most highly conserved regions of the extracellular domain. We conclude that 9 specific amino acids within the sequence 256-275 of hTSHr (-Y--CC-FKN-KK-R -) participate in the interaction of the hTSHr-extracellular domain with TSH. This may represent a site in which the nonconserved residues are involved in the binding of the beta-subunit and the conserved residues are involved in the binding of the common alpha-subunit or a region of the beta-subunit that is common to all glycoprotein hormones. PMID- 7983028 TI - Promotion of cell adhesion by single-stranded and triple-helical peptide models of basement membrane collagen alpha 1(IV)531-543. Evidence for conformationally dependent and conformationally independent type IV collagen cell adhesion sites. AB - Several regions within the triple-helical domain of type IV collagen function as cellular recognition sites. We have demonstrated previously that melanoma cell activities promoted by the alpha 1(IV)1263-1277 sequence are enhanced by triple helicity (Fields, C. G., Mickelson, D. J., Drake, S.L., McCarthy, J.B., and Fields, G.B. (1993) J. Biol. Chem. 268, 14153-14160), whereas Eble et al. reached similar conclusions for alpha 1 beta 1 integrin-mediated fibrosarcoma cell adhesion to [alpha 1(IV)]2 alpha 2(IV)434-472 (Eble, J. A., Golbik, R., Mann, K., and Kuhn, K. (1993) EMBO J. 12, 4795-4802). In the present study, we have examined the cell adhesion activities of a third region in type IV collagen. A single-stranded peptide (SSP) incorporating the alpha 1(IV)531-543 sequence promoted the adhesion of melanoma, ovarian carcinoma, and Jurkat cells in a dose dependent manner, with 40% cell adhesion observed at [SSP] = 1.8, 11.5, and 42.2 microM, respectively. Nearly identical results were obtained for cell adhesion to an all-D-enantiomer of the SSP, suggesting that the cell surface receptor(s) for this site do not discriminate based on chirality. The alpha 1(IV)531-543 sequence maintained its cell adhesion promoting activity when incorporated into a homotrimeric triple-helical polypeptide, although relative levels of adhesion were either slightly enhanced or slightly diminished compared with the SSP. Triple-helical conformation was thus not critical for cellular recognition of the alpha 1(IV)531-543 sequence. Single-site substitution experiments of the SSP showed no overall correlation between the biological effects of substitutions and SSP conformation. The SSP, D-SSP, triple-helical polypeptide, and SSP substitution results suggest that cell recognition of the alpha 1(IV)531-543 sequence is generally independent of substrate conformation. The present and prior studies indicate that "conformationally dependent" and "conformationally independent" cellular recognition sites exist within the triple-helical domain of type IV collagen. PMID- 7983029 TI - Mutations in the thioredoxin sites of protein disulfide isomerase reveal functional nonequivalence of the N- and C-terminal domains. AB - Protein disulfide isomerase (PDI), a foldase of the endoplasmic recticulum, is a multifunctional protein that catalyzes the formation and isomerization of disulfide bonds during protein folding. The wild-type protein contains two redox active thiol/disulfide sites near the N and C terminus that are homologous to the redox center of thioredoxin. Using site-directed mutagenesis, both cysteines of each of the thioredoxin-like centers, (C35S,C38S) and (C379S,C382S) were replaced by serines. In addition, a mutant PDI was constructed with all four of the active cysteines mutated to serine (C35S,C38S,C379S,C382S). The activity of the wild type and mutant proteins in the oxidative renaturation of reduced, denatured RNase was analyzed over a wide range of RNase concentrations, PDI concentrations, and glutathione redox buffers compositions. All mutants, including the construct with no functional thioredoxin centers, have measurable disulfide isomerase activity. Both of the thioredoxin-like sites contribute some to apparent steady state binding (Km) and catalysis at saturating substrate concentrations (kcat); however, their contributions are not equivalent. At saturating concentrations of RNase, the mutant with an inactivated C-terminal active site (kcat = 0.72 +/- 0.06 min-1) retains near wild-type activity (kcat = 0.76 +/- 0.02 min-1), while the N-terminal mutant exhibits a significantly lower kcat (0.24 +/- 0.01 min-1). The Km for RNase is elevated for the C-terminal mutant (Km = 29 +/- 4 microM) while the N-terminal mutant (Km = 7.1 +/- 1.1 microM) exhibits a wild-type Km (6.9 +/- 0.8 microM). The larger Km for the C-terminal mutant (4.2 times wild type) and the lower kcat of N-terminal mutant (32% of wild-type) suggest that the C-terminal region contributes more to apparent steady-state substrate binding, and the N-terminal region contributes more to catalysis at saturating concentrations of substrate. Despite their complementary roles in catalysis, the thioredoxin-like centers exhibit the same dependence on the glutathione redox buffer composition as evidenced by the equivalent K(ox) values for the wild-type (47 +/- 1 microM), N-terminal mutant (43 +/- 3 microM), and C-terminal mutant (44 +/- 1 microM). The mutant with both thioredoxin sites mutated displays a low but detectable level of disulfide-isomerase activity (0.5% of wild-type) that can be observed at high PDI concentrations. At high RNase concentrations (> or = 26 microM), wild-type PDI and all of the mutants catalyze intermolecular RNase aggregation in a nucleation growth reaction that is first order in PDI but fourth order with respect to RNase.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 7983030 TI - Identification of peptide binding residues in the extracellular domains of the AT1 receptor. AB - To locate essential determinants for angiotensin II binding, we have performed a systematic mutational analysis of the exterior domain of the AT1 receptor. Receptor mutants, deficient in peptide binding, were analyzed using radiolabeled nonpeptide ligand as an important tool. Two independent strategies for mutagenesis were employed: conservative segment exchange and point mutagenesis of evolutionarily conserved residues. Results from the conservative segment exchange in which 6-17 residues were replaced with chemically similar, yet different, amino acid sequences of the same length suggested that important peptide ligand binding epitopes are located in the N-terminal extension of the AT1 receptor, in particular adjacent to the top of transmembrane segment I (TM-I), and in the third extracellular loop, close to the top of TM-VII. The substitution of residues from either of these regions resulted in a 5,000-20,000-fold decrease in affinity for the peptide agonist angiotensin II (AII) and the peptide antagonist [Sar1,Leu8]AII without affecting the binding of nonpeptide antagonists. Alanine substitution of evolutionarily conserved residues demonstrated that peptide binding was dependent on several residues in the N-terminal extension, near the top of TM-I, a tyrosine residue located in extracellular loop 1, close to TM-II, and 2 aspartate residues positioned in extracellular loop 3 on the same face of an alpha-helical extension of TM-VII. In all cases the binding of nonpeptide antagonist was unaffected by these substitutions. It is concluded that important epitopes involved in angiotensin II binding are located around the top of transmembrane segments I, II, and VII which conceivably are in close spatial proximity in the folded receptor structure. PMID- 7983031 TI - Microtubule-associated protein kinase-2 phosphorylates and activates tyrosine hydroxylase following depolarization of bovine adrenal chromaffin cells. AB - Depolarization of cultured bovine adrenal chromaffin cells with KCl increased the activity of a proline-directed protein kinase that phosphorylates tyrosine hydroxylase. Characterization of the KCl-activated protein kinase activity revealed that it shared similar biochemical and chromatographic properties with the microtubule-associated protein-2 kinase/extracellularly regulated kinase (MAP/ERK) family of protein kinases. This protein kinase activity was found to elute from Mono Q, Superose, and phenyl-Sepharose columns under conditions described for MAP/ERK kinases, and active fractions were found to react with specific antibodies directed against ERKs. The KCl-activated protein kinase was found to phosphorylate the serine 31 site of endogenous bovine adrenal tyrosine hydroxylase. This phosphorylation resulted in an approximately 2-fold activation of tyrosine hydroxylase. PMID- 7983032 TI - Metabolism of the "Swedish" amyloid precursor protein variant in Madin-Darby canine kidney cells. AB - The 4-kDa beta-amyloid peptide (A beta), a major constituent of parenchymal amyloid deposits in Alzheimer's disease, is derived from larger amyloid precursor proteins (APP). We have examined the metabolism of APP in Madin-Darby canine kidney cells stably transfected with cDNA encoding either wild-type human APP-695 or human APP-695 that harbors the Swedish double mutation associated with familial early-onset Alzheimer's disease. Although approximately 90% of total soluble APP secreted from wild-type cells is secreted basolaterally following cleavage at the alpha-secretase site, soluble derivatives cleaved near or at the amino terminus of A beta (presumably the "beta-secretase" site) are preferentially secreted into the apical compartment of SWE cells. Concomitantly, levels of a specific A beta-containing carboxyl-terminal fragment are elevated in SWE cell lysates. Using domain-specific biotinylation and release assays, we failed to detect a beta-secretase-generated soluble derivative (APPs beta) released from the surface of SWE cells. However, APPs beta can be detected in SWE cell lysates, consistent with "beta-secretase" cleavage occurring in an intracellular compartment. Finally, we demonstrate that A beta is secreted into the basolateral compartment of SWE cells and that the majority of these A beta related species contains an amino-terminal aspartate residue (+1). PMID- 7983033 TI - Beta-NADH decreases the permeability of the mitochondrial outer membrane to ADP by a factor of 6. AB - Mitochondria with intact outer membrane (99% intact based on cytochrome c impermeability) were isolated and used to measure the permeability of their outer membrane to ADP. beta-NADH reduced the permeability in a concentration-dependent manner (KD = 87 +/- 5 microM) by a factor of 6. alpha-NADH and beta-NAD+ cannot mimic the action of beta-NADH. The mitochondrial outer membranes become rate limiting in the presence of beta-NADH at low, physiologically relevant, ADP concentrations (< 30 microM). beta-NADH has been shown to increase the voltage dependence of VDAC (a major pathway for metabolite transport across the outer membrane) in a reconstituted system and this may be the way it acts on the isolated mitochondria. Inhibition of beta-NADH dehydrogenases does not inhibit the action of beta-NADH indicating that it is not acting by delivering reducing equivalents. The ability of beta-NADH, produced by glycolysis, to inhibit mitochondrial function by reducing the permeability of the outer membrane may be one pathway responsible for the Crabtree effect. PMID- 7983034 TI - The phosphorylation state of tau in the developing rat brain is regulated by phosphoprotein phosphatases. AB - The paired helical filaments (PHFs) in Alzheimer's disease neurofibrillary tangles are composed of PHF-tau which is thought to be hyperphosphorylated because several residues in postmortem samples of PHF-tau and human fetal tau are phosphorylated while the corresponding sites are not phosphorylated in autopsy derived normal adult human brain tau. To determine how the phosphorylation of these sites is regulated, we isolated tau from rat brains at different embryonic and postnatal ages in the presence of okadaic acid to obtain tau in its most native in situ phosphorylation state. Fetal tau was highly phosphorylated from embryonic day 18 (E18) until postnatal day 11 (P11). Thereafter, the levels of fetal tau diminished as did its phosphorylation state concomitant with the appearance of the five adult tau isoforms. Several phosphorylation-dependent antibodies (i.e. AT270, AT8, AT180, T3P, and PHF1) that recognize PHF-tau also recognized these tau isoforms, albeit at reduced levels in the mature rat brain. This suggests that Thr172, Ser193, Thr222, Ser387, and Ser395 are normal sites of phosphorylation in rat brain tau. The inclusion of OK in the microtubule assembly buffers did not alter the ability of tau to bind microtubules at any age. However, phosphatases were activated and kinases were down-regulated in the rat brain after P12 since adult tau proteins were partially dephosphorylated at and beyond this time in the absence of OK. Protein phosphatase 2A (PP2A) and 2B (PP2B) activities in the adult rat brain extracts dephosphorylated tau efficiently, but protein phosphatases in extracts of the P6 rat brain did not have a similar effect. This suggests that the sensitivity of tau to OK after P12 may be regulated by the de novo induction of adult brain phosphatases. Finally, PP2A and/or PP2B in adult rat brain extracts dephosphorylated tau in a site specific manner. Thus, PP2A and PP2B (or closely related phosphatases) may regulate the phosphorylation state of adult tau isoforms in vivo, and the generation of PHF-tau in the AD brain may result from the abnormal inactivation of similar phosphatases. PMID- 7983035 TI - Production, purification, and characterization of recombinant maspin proteins. AB - Maspin, a novel mammary serine protease inhibitor, was shown to have tumor suppressing activity (Zou, Z., Anisowicz, A., Hendrix, M. J. C., Thor, A., Neveu, M., Sheng, S., Rafidi, K., Seftor, E., and Sager, R. (1994) Science 263, 526 529). In this paper, we report the production of recombinant glutathione S transferase-maspin fusion protein, expressed in the bacterium Escherichia coli, and recombinant maspin, expressed in the insect Spodoptera frugiperda cells. The fusion protein was purified by glutathione affinity chromatography. Maspin expressed in insect cells was purified by a combination of Bio-Rad AG1-2X anion exchange chromatography and heparin affinity chromatography. The recombinant maspin from insect cells was cleaved at the putative reactive center, as confirmed by protein sequencing. Both recombinant proteins demonstrated strong inhibitory effects on the invasion by two breast tumor cell lines across reconstituted basement membranes and such inhibitory effect was abolished in the presence of the polyclonal antibody made against the reactive center region of maspin. The trypsin-cleaved recombinant maspin did not inhibit invasion, indicating that the inhibitory activity requires the intact putative reactive center. This paper provides evidence that recombinant maspin protein itself inhibits invasion, and supports the role of maspin as a tumor suppressor. PMID- 7983036 TI - Allosteric effectors are required for subunit association in T4 phage ribonucleotide reductase. AB - Bacteriophage T4 encodes its own aerobic ribonucleotide reductase (RNR), which reduces ribonucleoside diphosphates to the corresponding deoxyribonucleoside diphosphates. T4 RNR is composed of homodimeric large (R1) and small (R2) subunits. Intricate regulation of enzymatic activity is accomplished by the binding of nucleotide effectors to R1. Berglund (Berglund, O. (1972) J. Biol. Chem. 247, 7270-7275) described similarities between T4 RNR and the corresponding enzyme from aerobic Escherichia coli. An important difference, however, is that T4 RNR forms a tight R1.R2 complex, while the E. coli R1 and R2 more readily dissociate. In this study we purified the phage R2 subunit from an overexpression vector constructed by Tseng et al. (Tseng, M., Hilfinger, J., He, P., and Greenberg, R. (1992) J. Bacteriol. 174, 5740-5744) and used this as an immunogen to generate polyclonal antiserum. Using co-immunoprecipitation techniques, we probed in vitro for interactions between the phage-induced R1 and R2 subunits. Our studies indicate that tight binding of the phage RNR subunits is completely dependent upon the known allosteric effectors of the enzyme. Once the R1.R2 holoenzyme has been formed it appears to be remarkably stable when in the presence of dATP. However, if dATP is removed, the R1.R2 complex readily dissociates. PMID- 7983037 TI - Sulfolobus acidocaldarius terminal oxidase. A kinetic investigation and its structural interpretation. AB - The thermoacidophilic archaebacterium Sulfolobus acidocaldarius possesses a very unusual terminal oxidase. We report original kinetic experiments on membranes of this microorganism carried out by stopped flow, using time-resolved optical spectroscopy combined with singular value decomposition analysis. The reduced oxidized kinetic difference spectrum of the Sulfolobus membranes is characterized by three significant peaks in the visible region at 605, 586, and 560 nm. The 605 nm peak and part of the 586-nm peak (cytochrome aa3-type quinol oxidase) are reduced synchronously by both ascorbate plus N,N,N',N'-tetramethyl-p phenylendiamine (TMPD) and dithionite, and they are very rapidly oxidized by molecular oxygen. A second pool of cytochromes seems to contribute to the 586-nm peak which is not reduced by ascorbate plus TMPD and reacts very slowly with dithionite. The b-type cytochromes (560 nm peak) are reduced by both reductants and are essentially "non-autoxidizable" at room temperature. Only one CO binding site with spectral features, kinetic properties, and ligand affinity not very dissimilar from those of mammalian cytochrome oxidase can be detected in the ascorbate-reduced membranes. On the contrary, a second CO binding site having unusual properties for aa3 terminal oxidases can be detected in the dithionite reduced membranes. PMID- 7983038 TI - Negative regulation of the human apolipoprotein A-I promoter by fibrates can be attenuated by the interaction of the peroxisome proliferator-activated receptor with its response element. AB - Fibrates have been reported to modulate plasma high density lipoprotein cholesterol and apolipoprotein (apo) A-I concentrations. Therefore, the molecular mechanisms underlying the regulation of human apoA-I gene expression by fibrates was investigated. Fenofibrate reduced the expression of a reporter gene driven by the DNA sequences between -192 and +91 (BC-P-chloramphenicol acetyltransferase; CAT) relative to the apoA-I gene transcription start site approximately 3-fold. The sequences involved in the down-regulation of apoA-I gene transcription by fenofibrate were localized between -41 and +91 (P-CAT) relative to the transcription start site. The reduction of the expression of BC-P-CAT was dose dependent and maximal at 500 microM (20 +/- 7%). Different peroxisome proliferators showed different levels of repression varying from 39 +/- 4% for fenofibrate, 43 +/- 5% for tetradecylthioacetic acid, 48 +/- 4% for bezafibrate, 54 +/- 2% for 5,8,11,14-eicotetraynoic acid, 76 +/- 2% for ciprofibrate, whereas Wy 14643 only marginally inhibited the expression of BC-P-CAT. By contrast, inclusion of sequences between -256 and -192 (ABC-P-CAT) attenuated the repression by fenofibrate. Furthermore, the apoA-IA site (-214 to -192; Awt-P CAT) could counteract the repression of P-CAT by fenofibrate in the presence of cotransfected mPPAR alpha (peroxisome proliferator-activated receptor). In addition, the acyl-CoA oxidase-peroxisome proliferator response element (PPRE) could substitute the wild-type A-site in blocking the fenofibrate-induced reduction of the apoA-I promoter by mPPAR alpha. The protective effect of PPAR on fenofibrate induced inhibition of apoA-I expression was abolished after mutation of the direct repeat in the A site (Am-P-CAT). Consistent with these functional data only the wild-type, but not the mutated A site bound PPAR/retinoic X receptor heterodimers in gel shift assays. These data suggest that certain peroxisome proliferators can reduce the expression of the apoA-I promoter in a PPAR-independent fashion, through modulation of factors interacting with sequences localized between -41 and +91 of the apoA-I gene transcription initiation site. This inhibitory effect can be overcome when PPAR interacts with a functional PPRE, such as the apoA-I A site or the acyl-CoA oxidase-PPRE. PMID- 7983039 TI - Two naturally occurring mutations in the kinase domain of insulin receptor accelerate degradation of the insulin receptor and impair the kinase activity. AB - We identified two novel heterozygous missense mutations of the insulin receptor gene: the Asp1179 mutation in one family and the Leu1193 mutation in two unrelated families with extreme insulin resistance. In these patients, the number of insulin receptors on the cell surface was found to be markedly decreased by insulin binding and surface labeling studies in transformed lymphocytes. Insulin binding to the transfected COS 7 cells and Rat-1 cells with both mutant cDNAs was also decreased to 5-31% of normal, and the mutant insulin receptors showed a markedly decreased kinase activity. Although biosynthetic labeling studies revealed that both mutant receptors were synthesized as 190-kDa proreceptors, the degradation of the mutant proreceptors was 2-fold faster than that of the wild type proreceptors. However, the degradation rate of the mutant receptors on the cell surface was comparable to that of wild type insulin receptor. These results suggest that the Asp1179 and Leu1193 mutations in the kinase domain are unique in causing decreased insulin receptor number on the cell surface by accelerated intracellular degradation, and that insulin resistance in these patients is mainly due to the decreased receptor number rather than impaired kinase activity. PMID- 7983040 TI - Activation of protein kinase C beta gene expression by gonadotropin-releasing hormone in alpha T3-1 cell line. Role of Ca2+ and autoregulation by protein kinase C. AB - The gonadotroph-derived alpha T3-1 cell line was used to investigate the effect of gonadotropin-releasing hormone (GnRH) upon conventional protein kinase C sub types (cPKCs) gene expression. Addition of the stable analog [D-Trp6]GnRH (GnRH A, 0.1 nM) resulted in a rapid increase (30 min) of the steady state levels of PKC beta, but not PKC alpha, mRNA levels, while PKC gamma is not expressed in the cells. The rapid stimulatory effect of GnRH-A was blocked by pretreatment with actinomycin D or with the GnRH antagonist (D-pGlu1, pC1Phe2,D-Trp3,6)GnRH and was not mimicked by thyrotropin-releasing hormone. Addition of the PKC activator 12-O tetradecanoylphorbol-13-acetate (TPA) resulted also in a rapid (30 min) and selective increase in PKC beta, but not PKC alpha, mRNA levels. In contrast, the calcium ionophore, ionomycin, increased rapidly (30 min) both PKC alpha and PKC beta mRNA levels, and its stimulatory effect on PKC beta was not additive with that of TPA. The rapid stimulatory effect of GnRH-A was blocked by the PKC inhibitor bisindolylmaleimide (GF 109203X) or by down-regulation of endogenous PKC. Similarly, the rapid effect of GnRH-A was abolished by the intracellular Ca2+ chelator 1,2-bis(O-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid (BAPTA) or by removal of extracellular Ca2+. Stimulation of PKC beta mRNA levels by ionomycin was only reduced by GF 109203X and was not affected by down-regulation of PKC. In contrast the effect of TPA on PKC beta mRNA levels was reduced by BAPTA and abolished by removal of Ca2+. We conclude that Ca2+ and PKC act sequentially during GnRH-A-induced PKC beta gene expression and that PKC beta gene expression induced by GnRH-A is autoregulated by PKC. PMID- 7983041 TI - Identification of phosphorylation sites unique to the B form of human progesterone receptor. In vitro phosphorylation by casein kinase II. AB - The human progesterone receptor (PR), a member of the steroid/thyroid receptor superfamily of ligand-activated transcription factors, is expressed in most tissues as two forms that exhibit differential transcriptional activation potentials, full-length PR-B and NH2-terminally truncated PR-A. In human breast cancer cells (T47D) both forms of PR are constitutively phosphorylated but phosphorylation is increased in response to hormone treatment, suggesting that this modification has a role in regulating the activation state of the receptor. To more directly define the functional role of phosphorylation in the action of A and B receptors requires knowledge of the phosphorylated amino acid residues and the protein kinase(s) involved. Toward this end we have developed a strategy that combines isolation of PR phosphotryptic peptides by reverse phase high performance liquid chromatography, secondary analytical protease digestion, manual Edman degradation, and release of 32P that resulted in identification of two major phosphorylation sites, Ser81 and Ser162. Both sites are located in the amino-terminal region unique to PR-B, and one of these sites (Ser81) is encompassed in a casein kinase II (CKII) consensus sequence. Although human PR contains 11 potential CKII consensus sequences, CKII in vitro phosphorylated purified PR-B only at Ser81 suggesting that this may be an authentic site for CKII in vivo. PMID- 7983042 TI - Protoporphyrin IX, an endogenous ligand of the peripheral benzodiazepine receptor, potentiates induction of the mitochondrial permeability transition and the killing of cultured hepatocytes by rotenone. AB - The peripheral benzodiazepine receptor (PBzR) is associated with the outer mitochondrial membrane. Protoporphyrin IX (PPIX), an endogenous substance with high affinity for the PBzR, induced the inner membrane permeability transition (MPT) in respiring liver mitochondria de-energized by carbonyl cyanide p trifluoromethoxyphenylhydrazone. Cyclosporin A (CyA), an inhibitor of the permeability transition, prevented this effect. In cultured hepatocytes, the MPT was measured as an increased [3H]sucrose-accessible space sensitive to CyA. Nanomolar concentrations of PPIX potentiated the induction of the MPT and the extent of cell killing in hepatocyte cultures de-energized by rotenone. CyA prevented the enhanced cell killing by PPIX. PPIX did not increase the rate or extent of ATP depletion, the loss of the mitochondrial membrane potential, or the accumulation of long chain acyl-CoA thioesters. The association of the PBzR with the voltage-dependent anion channel of the outer mitochondrial membrane and with the adenine nucleotide carrier of the inner membrane suggests that this complex mediates the transport of PPIX across the mitochondrial membranes. In turn, this same complex participates in the MPT. Thus, the same structural complex (PBzR, voltage-dependent anion channel, and adenine nucleotide carrier) can interact with the endogenous substrate PPIX to result in different functional consequences depending on the state of mitochondrial energization. PMID- 7983043 TI - Low frequency vibrational modes of oxygenated myoglobin, hemoglobins, and modified derivatives. AB - The low frequency resonance Raman spectra of the dioxygen adducts of myoglobin, hemoglobin, its isolated subunits, mesoheme-substituted hemoglobin, and several deuteriated heme derivatives are reported. The observed oxygen isotopic shifts are used to assign the iron-oxygen stretching (approximately 570 cm-1) and the heretofore unobserved delta (Fe-O-O) bending (approximately 420 cm-1) modes. Although the delta (Fe-O-O) is not enhanced in the case of oxymyoglobin, it is observed for all the hemoglobin derivatives, its exact frequency being relatively invariable among the derivatives. The lack of sensitivity to H2O/D2O buffer exchange is consistent with our previous interpretation of H2O/D2O-induced shifts of v(O-O) in the resonance Raman spectra of dioxygen adducts of cobalt substituted heme proteins; namely, that those shifts are associated with alterations in vibrational coupling of v(O-O) with internal modes of proximal histidyl imidazole rather than to steric or electronic effects of H/D exchange at the active site. No evidence is obtained for enhancement of the v(Fe-N) stretching frequency of the linkage between the heme iron and the imidazole group of the proximal histidine. PMID- 7983044 TI - Targeting DNA-binding drugs to sequence-specific transcription factor.DNA complexes. Differential effects of intercalating and minor groove binding drugs. AB - Intercalating, minor groove binding, and covalently bonding drugs were evaluated by mobility shift assays for their ability to interfere with transcription factors binding to their respective DNA recognition sequences. The Cys2His2 zinc finger proteins EGR1, WT1, and NIL2A, the basic leucine-zipper protein wbJun/wbFos, and the minor groove binding protein hTBP were chosen as representative transcription factors. Their DNA recognition sites include G/C rich, mixed, and A/T-rich sequences. The intercalators nogalamycin and hedamycin, and the G/C-specific minor groove binding drug chromomycin A3 were the most potent drugs, preventing transcription factor.DNA complex formation at concentrations less than 1 microM. Similar concentrations of chromomycin A3 disrupted preformed complexes while nogalamycin and hedamycin were 50-fold less potent if proteins were allowed to bind DNA prior to drug treatment. Echinomycin inhibited EGR1.DNA complex formation 50% at 5 microM but had little effect on the formation of NIL2A.DNA complexes. Conversely, doxorubicin was found to inhibit NIL2A complex formation 50% at less than 1 microM, but did not achieve this level of inhibition of EGR1/DNA complex formation even at 50 microM. The A/T-directed minor groove binding drugs, while inhibiting hTBP at submicromolar concentrations, had no effect on either EGR1 or NIL2A. PMID- 7983046 TI - Characterization of a human locus in transition. AB - The spermatid-specific nucleoprotamine genes PRM1 and PRM2 and the transition protein gene TNP2 are clustered at a single site on human chromosome 16p13.2. To begin to understand the mechanism governing their genesis and coordinate regulation the primary sequence of this approximately 40.6 kilobase region was determined. This cluster of genes is embedded within a series of repetitive elements, including numerous Alu elements distributed at a frequency of > 1 Alu element/kilobase. Multiple Alu elements have integrated into separate truncated L1 sequences within this region. Many of these Alu elements are tandemly inserted or clustered. The role of repetitive elements in the genomic organization and evolution of this gene cluster is discussed. Computer-assisted sequence analysis revealed the presence of structural sequence elements often associated with the boundary regions of active transcriptional domains. Further analysis identified a CpG island at the 3' end of this segment of chromosome 16 and other candidate coding segments within this region indicative of an additional linked gene. These sequence landmarks are commensurate with the complexity of the region. PMID- 7983045 TI - Functional studies of P-glycoprotein in inside-out plasma membrane vesicles derived from murine erythroleukemia cells overexpressing MDR 3. Properties and kinetics of the interaction of vinblastine with P-glycoprotein and evidence for its active mediated transport. AB - Active [3H]vinblastine (VBL) transport (efflux) was documented for inside-out plasma membrane vesicles from murine erythroleukemia cells (MEL/VCR-6) resistant to vinca alkaloids and overexpressing MDR 3 P-glycoprotein (P-gp) 80-fold. Uptake of [3H]VBL at 37 degrees C by these inside-out vesicles, but not rightside-out vesicles or inside-out vesicles from wild-type cells, was obtained in the form of a rapid, initial phase (0-1 min) and a slower, later phase (> 1 min). The rapidity of each phase correlated with relative P-gp content among different MEL/VCR cell lines. The initial MDR-specific phase was temperature- and pH dependent (optimum at pH 7), osmotically insensitive, and did not require ATP. The second MDR-specific phase was temperature-dependent, osmotically sensitive, and strictly dependent upon the presence of ATP (Km = 0.37 +/- 0.04 mM). Although other triphosphate nucleotides were partially effective in replacing ATP, the nonhydrolyzable analogue ATP gamma S (adenosine 5'-O-(thiotriphosphate)) was ineffective. This time course appears to represent tandem binding of [3H]VBL by P gp and its mediated transport, with the latter process representing the rate limiting step. In support of this conclusion, both binding and transport were inhibited by verapamil, quinidine, and reserpine, all known to be inhibitors of photoaffinity labeling of P-gp, but only transport was inhibited by C219 anti-P gp antibody or orthovanadate. Although the rate of transport of [3H]VBL was 7-7.5 fold lower than the rate of binding (Vmax = 104 +/- 15 pmol/min/mg protein, Kon = 1.5 - 2 x 10(5) mol-1 s-1) to P-gp, each phase exhibited saturation kinetics and values for apparent Km and KD for each process were approximately the same (215 +/- 35 and 195 +/- 30 nM). Intravesicular accumulation of [3H]VBL was almost completely eliminated by high concentrations of nonradioactive VBL, suggesting that simple diffusion does not contribute appreciably to total accumulation of [3H]VBL in this vesicle system. This could be at least partially explained by the fact that these inside-out vesicles under the conditions employed did not maintain a P-gp mediated pH gradient. However, ATP-dependent, intravesicular accumulation of osmotically sensitive [3H]VBL occurred against a substantial permeant concentration gradient in both a time- and concentration-dependent manner consistent with an active, saturable process. PMID- 7983047 TI - Importance of the region around lysine 196 for catalytic activity of adenylyl cyclase from Escherichia coli. AB - Escherichia coli adenylyl cyclase contains no sequence that corresponds to the previously defined ATP/GTP binding consensus (A,G)XXXXGK(S,T). Using a search for lysine residues located adjacent to glycine residues, three regions that were possible candidates for part of the ATP binding site were identified. These were the residues located at positions 59, 90, and 196. A plasmid vector capable of overexpressing the cya gene under the control of the lambda PL promoter was mutated at these three loci to convert those lysine residues to methionine. Assays for catalytic activity of the mutated hyperexpressed proteins revealed that only the mutation at position 196 led to loss of activity. Photoaffinity labeling experiments using 8-azido-ATP provided evidence that the loss of activity was associated with a loss of the capability of the enzyme to bind ATP. A further series of replacement mutations in the hyperexpression vector was created at position 196. Assays of the adenylyl cyclase activity of the mutated proteins showed that replacement of lysine 196 by arginine led to minimal change in the activity. Replacements by histidine, glutamine, or glutamic acid resulted in approximately 10-20-fold reductions in the activity; replacements by methionine, isoleucine, or aspartic acid resulted in total loss of activity. When the mutated forms of the cya gene were expressed under the control of the cya promoter, the activity of the wild-type protein was higher than that of all the mutants, including the arginine replacement mutant. All of the mutants that retained activity also retained the capability of adenylyl cyclase to be stimulated by either inorganic orthophosphate or GTP. A helical wheel analysis of the region of adenylyl cyclase around lysine 196 revealed a structure compatible with an amphipathic helix with one face enriched with basic amino acid residues. Assays for adenylyl cyclase activity of a series of replacement mutations of residues on the hydrophilic face of the helix (R188I, R192I, G195I) as well as on the hydrophobic face (R197I) indicated that the R188I, G195I, and K196I replacement mutants were inactive, and R192I was approximately 30% as active as the wild-type, while the R197I mutant was equivalent to the wild-type control. A model is suggested for a unique binding motif in E. coli adenylyl cyclase in which there is a repetition of 3 basic residues on one face of a helix where there is an interaction with the three phosphate groups of ATP. PMID- 7983048 TI - Molecular characterization of human and mouse photoreceptor guanylate cyclase activating protein (GCAP) and chromosomal localization of the human gene. AB - Guanylate cyclase-activating protein (GCAP) is a novel Ca(2+)-binding protein that stimulates synthesis of cGMP in photoreceptors. Molecular cloning of human and mouse GCAP cDNA revealed that the known mammalian GCAPs are more than 90% similar, consist of 201-205 amino acids, and contain three identically conserved EF hand Ca2+ binding sites. The sequence homology with recoverin, a related photoreceptor Ca(2+)-binding protein, is less than 35%. In situ hybridization in primate retinas shows that the GCAP gene is expressed exclusively in photoreceptor inner segments. To investigate the GCAP gene structure, we probed 10 eucaryotic genomic DNAs with a bovine GCAP cDNA under stringent conditions. The results demonstrate that the GCAP gene has been well conserved during evolution of vertebrate species and that each gene is most likely present as a single copy. By genomic cloning, polymerase chain reaction, mapping, and direct sequencing, we show that the human GCAP gene spans approximately 6 kilobases of genomic DNA, and consists of four exons (> 250, 146, 94, and 800 base pairs) separated by three introns (4.5 kilobases, 370 base pairs, and 347 base pairs). Using human/hamster hybrid panels and fluorescent in situ hybridization, the GCAP gene was localized to the short arm of chromosome 6 (p21.1). PMID- 7983049 TI - c-Jun represses transcription of the human chorionic gonadotropin alpha and beta genes through distinct types of CREs. AB - Chorionic gonadotropin (CG) is a heterodimeric placental hormone encoded by separate alpha and beta subunit genes that is essential for the maintenance of pregnancy. The production of CG is stimulated by DNA synthesis inhibitors and by cAMP. The present study demonstrates that the proto-oncogene c-jun represses transcription of the human CG alpha and CG beta promoters. c-Jun repressed the CG alpha promoter through a canonical cAMP response element (CRE) that is known to bind c-Jun and other members of the B-Zip transcription factor family. In the CG beta promoter, two adjacent sites, CRE1 (-299 to -289) and CRE2 (-240 to -219), conveyed cAMP responsiveness via sequences that are distinct from the canonical element, TGACGTCA. Mutations within CG beta CRE1 or CRE2 reduced or abolished, respectively, c-Jun-mediated repression. Although the CG beta CREs do not contain consensus sequences previously described to bind c-Jun, CRE2 bound c-Jun and c Fos in electrophoretic mobility shift assays. Supershift assays, using anti-JUN antibody, demonstrated that Jun formed part of the native complex that binds the CRE2 in JEG-3 cells. A series of c-Jun mutants were used to analyze the transcription factor domains required for repression of the CG subunit promoters. The DNA binding and leucine zipper domains of c-Jun as well as the amino terminus, were required for repression of both subunit promoters. Thus, both the CG alpha and CG beta genes are repressed by c-Jun through promoter regions that convey cAMP-induced transcription, although these DNA sequences are unrelated. PMID- 7983050 TI - Visualization and function of vimentin phosphorylation by cdc2 kinase during mitosis. AB - To investigate the role of intermediate filament (IF) protein phosphorylation by cdc2 kinase during mitosis, we developed a monoclonal antibody 4A4 recognizing Ser55-phosphorylated vimentin. Western blotting indicated that this antibody reacted with vimentin phosphorylated by cdc2 kinase but not with non phosphorylated vimentin or with vimentin phosphorylated by other kinases such as cAMP-dependent protein kinase, protein kinase C, or Ca(2+)-calmodulin-dependent protein kinase II. Immunofluorescence and immunoelectron microscopy showed that vimentin Ser55 residues distributed in the entire cytoplasmic vimentin filament system are phosphorylated when the cells enter mitosis and dephosphorylated in cytokinesis. All cell lines examined showed a similar appearance of immunoreactivity with antibody 4A4. Fractionation of mitotic cell extracts on Mono-Q Sepharose revealed a single peak of vimentin Ser55 kinase activity, and the anti-p34cdc2 antibody reacted with the 34 kDa band in the kinase containing fractions. Vimentin Ser55 kinase activities were nil in the interphase cell extract. Immunofluorescent evidence using antibody 4A4 and biochemical analysis using vimentin Ser55 peptide showed that the degree of disassembly of vimentin filament of various cell types at early mitotic phase correlated well with the amount of mitotically activated cdc2 kinase. PMID- 7983051 TI - Insulin receptor substrate-1 (IRS1) and Shc compete for a limited pool of Grb2 in mediating insulin downstream signaling. AB - Expression of the insulin receptor substrate-1 (IRS1) or Shc cDNA resulted in both increased protein and insulin-stimulated tyrosine phosphorylation of IRS1 and Shc proteins, respectively. Although expression of Shc had no significant effect on insulin-stimulated mitogen-activated protein (MAP) kinase gel shift or c-fos transcriptional activation, expression of IRS1 inhibited these responses. The effect of IRS1 expression on the formation of multisubunit signaling complexes was determined by a series of indirect co-immunoprecipitations. Grb2 immunoprecipitation from IRS1-transfected and insulin-treated cells demonstrated an increased coimmunoprecipitation of Syp and the p85 regulatory subunit of the phosphatidylinositol 3-kinase. Similarly, cell extracts immunoprecipitated with a p85 antibody displayed an increased co-immunoprecipitation of Syp and Grb2. However, expression of IRS1 increased the extent of Grb2 associated with IRS1 with a concomitant reduction in the amount of Grb2 associated with Shc. Furthermore, increased expression of Shc reduced the amount of Grb2 bound to IRS1 with a concomitant increase in Grb2 associated with Shc. Together, these data demonstrate that IRS1 and Shc compete for a limited cellular pool of Grb2, and insulin activation of MAP kinase and c-fos transcription predominantly occur through the Shc-Grb2 signaling pathway. PMID- 7983052 TI - Synergistic membrane interactions of the two C2 domains of synaptotagmin. AB - Synaptotagmin, an integral membrane protein localized to secretory vesicles, has been implicated in the docking and fusion steps in calcium-regulated exocytosis. The large cytoplasmic domain contains two C2 motifs, each similar to the Ca2+ and phospholipid binding domain of protein kinase C. To study the membrane binding and aggregating properties of these C2 domains, three recombinant fragments of rat synaptotagmin I were expressed in Escherichia coli and purified. A recombinant protein containing both C2 domains (p65 1-5) was found to bind to and aggregate bovine chromaffin granules in a calcium-dependent manner, with half maximal binding and aggregation occurring at approximately p Ca2+ = 4.2. However, recombinant proteins containing either the first (p65 1-3) or second (p65 3-5) C2 domain alone were not able to bind to the granules, indicating that both C2 domains are required for binding to chromaffin granules. p65 1-5 also bound to and aggregated liposomes made from chromaffin granule lipid extracts, as well as granules treated extensively with trypsin, suggesting that p65 1-5 binding to granules is mediated by the lipids in the granule membrane and not the granule membrane proteins. Although p65 1-3 and p65 3-5 did not bind to granules or lipids extracted from granules, both did bind to phosphatidylserine (PS)/phosphatidylcholine (PC) vesicles (10%-40%PS). Half-maximal binding of p65 1 3 to vesicles occurred at approximately p Ca2+ = 5.2, while p65 3-5 appeared to bind independently of calcium over the range of pCa2+ = 5.5-2.8. p65 1-5 exhibited binding to PS/PC vesicles with characteristics of both the smaller proteins, displaying some binding in EGTA and increased binding in calcium. Larger amounts of p65 1-5 bound to PS/PC vesicles than of either of the smaller fragments. These results suggest that the two C2 domains of synaptotagmin act synergistically to promote binding to biological membranes and to affect calcium sensitivity and membrane binding capacity. PMID- 7983053 TI - An in vivo assay for members of the cAMP response element-binding protein family of transcription factors. AB - The CREB/ATF family of dimeric basic/leucine zipper (bZIP) transcription factors have been implicated in signal transduction by several agents including intracellular cAMP. The ubiquity of the cAMP-signaling pathway in mammalian cells has made it difficult to assay individual family members in their native form and dissect their roles in signal transduction. In light of observations that ATF1 exhibits several cell-specific characteristics and is allosterically regulated, the above problem has represented a particular limitation for studying ATF1. To address this we have exploited the modular nature of the bZIP domain to design fusion proteins that closely resemble native ATF1 but have altered DNA binding and dimerization specificity. The activity of these novel proteins can be monitored following their introduction into a cAMP-responsive cell type. Thus we describe an assay for members of the CREB family that should be generally applicable in a range of cell types and to other bZIP protein families. PMID- 7983054 TI - Molecular cloning and characterization of a cDNA encoding pea monodehydroascorbate reductase. AB - Monodehydroascorbate radicals are generated in plant cells enzymatically by the hydrogen peroxide scavenging enzyme, ascorbate peroxidase, and nonenzymatically via the univalent oxidation of ascorbate by superoxide, hydroxyl, and various organic radicals. Regeneration of ascorbate is achieved by monodehydroascorbate reductase (EC 1.6.5.4) using NAD(P)H as an electron donor or, alternatively, by a set of two coupled reactions requiring dehydroascorbate reductase, glutathione reductase, glutathione, and NAD(P)H. As monodehydroascorbate reductase is a key enzyme in maintaining reduced pools of ascorbate, an important antioxidant, we undertook this study to learn more about its structure, function, and regulation. Herein we report the molecular cloning and characterization of a cDNA encoding monodehydroascorbate reductase of pea (Pisum sativum L.). The cDNA encodes a 433 amino acid polypeptide that shows, respectively, 73 and 87% identity with peptide fragments from soybean and cucumber monodehydroascorbate reductase. Monodehydroascorbate reductase contains the NAD(P)H and FAD binding domains of other flavin oxidoreductases. The cloned enzyme lacks a transit peptide, but the sequence of the carboxyl terminus is Ser-Lys-Ile, similar to the targeting motif found in peroxisomal proteins. When expressed in Escherichia coli fused to maltose-binding protein, monodehydroascorbate reductase has enzymatic properties comparable with purified soybean and cucumber monodehydroascorbate reductase. Northern blot analysis shows that the monodehydroascorbate reductase transcript is 1.6 kilobase in size and is expressed at relatively low levels in all plant tissues examined. PMID- 7983055 TI - Analysis of subunit interaction by introducing disulfide bonds at the dimerization domain of Hin recombinase. AB - The Hin recombinase exists as a homodimer in solution and binds to its recombination site (hix) as a dimer (Glasgow, A. C., Bruist, M. F., and Simon M. I. (1989) J. Biol. Chem. 264, 10072-10082). Previous mutational and structural studies of related proteins suggested the location of a putative dimerization domain. In order to probe the function of this region of the protein, cysteine residues were introduced at each of the seven positions comprising the domain. Proteins containing cysteine substitutions at positions 101 and 104 were able to form disulfide bonds spontaneously in crude extracts. M101C showed wild type inversion activity only if the cysteine residue was not engaged in a disulfide bond. This mutant, which is cross-linked by a disulfide bond at the dimeric interface, was found to be defective in the DNA cleavage step during inversion. H107C displayed the wild type DNA cleavage activity, even though its DNA binding activity was not detected by three different binding assays. This suggests that it maintains specificity for DNA binding but dissociates rapidly after binding. The remaining inversion-defective mutants fell into two groups. One group lost its capacity to specifically bind to DNA (G102C, F105C, and F106C), and the other group (R103C and F104C), while able to bind to DNA, was defective in subsequent steps of the inversion reaction. Characteristics of these mutants led me to postulate that movement of subunits at the dimerization interface is critical during DNA binding and during formation of the invertasome, which is the recombination structure. Furthermore, the relative position of subunits within the dimer may be important for maintaining stable DNA binding. PMID- 7983056 TI - Purification and characterization of UDP-GlcNAc:IV3 beta Gal-Gb4Cer beta-1,6 GlcNAc transferase from mouse kidney. AB - The Gsl-5 gene mapped on mouse chromosome 19 controls the expression of IV6 beta Gal beta 1-4(Fuc alpha 1-3)GlcNAc, IV3 beta Gal-Gb4Cer in mouse kidney through regulation of the activity of UDP-GlcNAc:IV3 beta Gal-Gb4Cer beta-1,6-Glc-NAc transferase (GNT), which transfers GlcNAc to the C-6 position of GalNAc of IV3 beta Gal-Gb4Cer (GL-X). Here we report that GNT has been purified to apparent homogeneity from mouse kidney by means of preparation of a microsomal fraction, solubilization with Triton X-100, and sequential column chromatographies on CM Sepharose, UDP-hexanolamine-Sepharose, and Gg4Ose-Aminocellulo-fine. GNT purified 11,000-fold from the microsomal fraction exhibited a specific activity of 26.15 mumol/min/mg protein and an apparent molecular mass of 50 kDa on SDS polyacrylamide gel electrophoresis. The Km values for UDP-GlcNAc and GL-X were 0.36 and 0.11 mM, respectively. Among glycolipids tested as substrates, GL-X was the best and Gg4Cer the next best, but Lc3Cer, Gb4Cer, and GM1 did not act as a substrate. GNT was also able to transfer GlcNAc to Gal beta 1-3GalNAc beta 1 benzyl and Gal beta 1-3GalNAc alpha 1-p-nitrophenyl at C-6 of GalNAc through beta linkage but not to GlcNAc beta-3GalNAc alpha 1-p-nitrophenyl. The purified GNT was digested with lysyl endopeptidase, and four peptides generated were sequenced. The sequence of four peptides spanning 35 amino acid residues in total exhibited 80% homology with that of the reported human core 2 GlcNAc transferase. PMID- 7983057 TI - Functional analysis of a transactivation domain in the thyroid hormone beta receptor. AB - Hormone-dependent transcriptional activation (AF-2) by the thyroid hormone beta receptor (TR beta) localizes to its carboxyl-terminal domain. A putative transactivation sequence within this domain was analyzed by mutating individual residues to alanine. Mutant receptor carboxyl-terminal domains were tested coupled to the heterologous DNA binding domain of Gal4. A single mutant receptor (E460A) showed normal hormone binding and activation, whereas several others (P453A, F455A, L456A, F459A) exhibited impaired transactivation which correlated with their reduced ligand binding. Two mutations (L454A, E457A) were able to dissociate these properties, generating transcriptionally defective mutant proteins with preserved hormone binding. A further conservative substitution (E457D) was also nonfunctional, and these three mutations were equally deleterious when tested in the context of full-length TR beta with a natural thyroid hormone response element containing promoter. This loss of activity was not due to altered DNA binding or expression of mutant receptors in cultured cells. They also retained the ability to recruit VP16-tagged retinoid X receptor in vivo as well as bind the basal transcription factors TFIIB and TBP in vitro. Our observations indicate that conserved hydrophobic (Leu454) and charged (Glu457) residues mediate AF-2 activity of TR beta, possibly via a co-activator that has yet to be identified. PMID- 7983058 TI - Serum-inducible factors binding to an activating transcription factor motif regulate transcription of the Id2A promoter during myogenic differentiation. AB - Expression of Id, a dominant negative regulator of helix-loop-helix transcription factors, is tightly regulated during cellular differentiation. In this study, we have defined the sequences responsible for the transcriptional regulation of the human Id2A gene. 5' deletion and site-specific mutation analyses of the Id2A promoter showed that both an Sp-1 site and an activating transcription factor (ATF)-like site (referred to as IdATF sites) are required for expression in C2 cells, whereas these sites are not essential for the expression in nonmuscle cells, including HeLa and 10T1/2 cells. Gel shift assays revealed nuclear factors with specific binding to IdATF sites in both C2 and HeLa cells, which are efficiently competed by either legitimate ATF- or AP-1 binding sites. DNA binding activity to IdATF sites was clearly decreased during C2 cell differentiation and rapidly reactivated by treatment with either phorbol 12-myristate 13-acetate or serum, which correlated with the induction of endogenous Id2A mRNA expression. In addition, we show that overexpression of the catalytic domain of protein kinase C leads to the activation of the Id2A promoter through IdATF sites in C2 cells. These results suggest a model in which down-modulation of IdATF site binding activity by mitogen depletion contributes to the down-regulation of Id2A gene expression that is essential for myogenic differentiation. PMID- 7983059 TI - Structure-function studies on recombinant human macrophage colony-stimulating factor (M-CSF). AB - Human macrophage colony-stimulating factor (M-CSF) is a homodimeric cytokine that is a member of a structurally related family of hormones defined by an unusual up up-down-down alpha-helical bundle. To identify regions on the surface of M-CSF that might interact with the M-CSF receptor, single and double amino acid substitutions were introduced into a truncated form of human M-CSF alpha by site directed mutagenesis, and the homodimeric M-CSF analogs were purified and characterized. Certain substitutions in the region before and in helix A and in helix C decreased specific bioactivity and correlated with an approximately equivalent reduction in M-CSF receptor affinity. The most dramatic change was observed in an analog in which residues His-9 and His-15 were replaced with alanines, resulting in a 9,100-fold decrease in specific bioactivity. X-ray crystallographic analysis of this M-CSF alpha H9A,H15A analog at a resolution of 2.5 A revealed no significant changes in structure other than the expected new side chains at residues 9 and 15. Analogs containing only one of these two histidine substitutions exhibited a decrease in specific bioactivity of 6- and 1200-fold for the H9A and H15A mutations, respectively. It appears that selected amino acids in the NH2-terminal region of M-CSF and possibly portions of the surface formed by helices A and C are significantly involved in interactions with the M-CSF receptor. PMID- 7983060 TI - Insulin-induced activation of phosphatidyl inositol 3-kinase. Demonstration that the p85 subunit binds directly to the COOH terminus of the insulin receptor in intact cells. AB - Insulin activates the insulin receptor tyrosine kinase to phosphorylate signaling molecules such as insulin receptor substrate-1 (IRS-1). Phosphorylated IRS-1 binds to SH2 domains in the p85 regulatory subunit of phosphatidyl inositol (PI) 3-kinase, thereby stimulating the catalytic activity of PI 3-kinase. For most growth factor receptor tyrosine kinases (including receptors for epidermal growth factor and platelet-derived growth factor), the p85 regulatory subunit of PI 3 kinase binds directly to phosphorylated YXXM motifs contained in the cytoplasmic domain of the receptor itself. Previous studies in cell-free systems have shown that the phosphorylated YHTM sequence (amino acid residues 1322-1325) in the COOH terminus of the insulin receptor has the ability to bind to the p85 subunit of PI 3-kinase, thereby activating the enzyme. In this investigation, we demonstrate the occurrence of the same direct binding interaction in intact cells. Subsequent to insulin-stimulated phosphorylation of the insulin receptor, a complex is formed that contains the insulin receptor and PI 3-kinase. This complex can be immunoprecipitated by antibodies directed against either the insulin receptor or the p85 subunit of PI 3-kinase. The delta 43 mutant insulin receptor that lacks 43 amino acids at the COOH terminus does not bind p85. In addition, the delta 43 truncation impairs the ability of the receptor to mediate the activation of PI 3 kinase. Thus, by binding directly to p85, the phosphorylated YHTM motif in the COOH terminus of the insulin receptor contributes partially to mediating the effect of insulin to activate PI 3-kinase. PMID- 7983062 TI - Sarcoplasmic reticulum calcium pump in cardiac and slow twitch skeletal muscle but not fast twitch skeletal muscle undergoes phosphorylation by endogenous and exogenous Ca2+/calmodulin-dependent protein kinase. Characterization of optimal conditions for calcium pump phosphorylation. AB - We have demonstrated recently that in cardiac sarcoplasmic reticulum (SR), a membrane-associated Ca2+/calmodulin-dependent protein kinase (CaM kinase) phosphorylates and activates the Ca(2+)-pumping ATPase (Ca(2+)-ATPase) in addition to phosphorylating the previously characterized substrates, phospholamban, and Ca2+ release channel (ryanodine receptor) (Xu, A., Hawkins, C., and Narayanan, N. (1993) J. Biol. Chem. 268, 8394-8397). The present study shows that a CaM kinase regulatory system capable of modulating SR Ca2+ pump activity through direct phosphorylation of the Ca(2+)-ATPase is functional in slow twitch but not fast twitch skeletal muscle. Incubation of SR vesicles isolated from rabbit slow twitch (soleus) and fast twitch (adductor magnus) skeletal muscles in the presence of Ca2+ and calmodulin resulted in phosphorylation of the Ca(2+)-ATPase in slow twitch muscle SR but not in fast twitch muscle SR. Exogenous CaM kinase II, which stimulated phosphorylation of the cardiac and slow twitch muscle SR Ca(2+)-ATPase, failed to phosphorylate fast twitch muscle SR Ca(2+)-ATPase. These observations demonstrate that CaM kinase catalyzed phosphorylation of the Ca2+ pump is isoform-specific since heart and slow twitch muscle express the same Ca(2+)-ATPase isoform (SERCA2a), which is distinct from that of fast twitch muscle (SERCA1). As in the case of cardiac SR Ca(2+)-ATPase, phosphorylation of the slow twitch muscle SR Ca(2+)-ATPase (occurring at a serine residue) resulted in a 2-fold increase in catalytic activity of the enzyme without alteration in its Ca2+ sensitivity. In addition, Ca2+/calmodulin-dependent prephosphorylation of slow twitch muscle SR resulted in a greater than 2-fold increase in its Ca2+ transport activity. In both cardiac and slow twitch muscle SR, phosphorylation of the Ca(2+)-ATPase by the endogenous CaM kinase occurred rapidly (maximum within 2 min at 37 degrees C), had similar pH optimum (8.5-9.0), temperature optimum (30 degrees C), and calmodulin concentration-dependence (k0.5 50-60 nM). cAMP-dependent protein kinase did not phosphorylate the Ca(2+)-ATPase appreciably in either cardiac or slow twitch muscle SR. These findings suggest a muscle-specific role for the membrane associated CaM kinase in the modulation of Ca2+ uptake and release functions of the SR. In cardiac and slow twitch muscle, phosphorylation of the SR Ca(2+) ATPase by CaM kinase might provide a novel mechanism for the modulation of the enzymatic and Ca2+ transport functions of this enzyme. PMID- 7983061 TI - Vaccinia virus DNA polymerase. In vitro analysis of parameters affecting processivity. AB - The polymerization and proofreading activities of the vaccinia virus DNA polymerase reside within a 116-kDa catalytic polypeptide. We report here an investigation of the intrinsic processivity of this enzyme on both natural and homopolymeric DNA templates. Inclusion of the Escherichia coli helix destabilizing protein allowed the viral enzyme, which lacks strand displacement activity, to utilize a singly primed M13 DNA template. In the presence of either 10 mM MgCl2 or 1 mM MgCl2 + 40 mM NaCl, synthesis was achieved in a highly distributive manner. RFII formation required a significant excess of enzyme, and < or = 10 nucleotides (nt) were added per primer-template binding event. The apparent rate of primer elongation varied with the enzyme/template ratio and reached a maximum of 8 nt/s. A similar lack of processivity was observed on a poly(dA390)-oligo(dT12-18) template. In contrast, highly processive synthesis was achieved on both templates in the presence of 1 mM MgCl2 and the absence of NaCl. A primer extension rate of 30 nt/s was observed, and > or = 2000 nt were added per binding event. These studies suggest that the catalytic polypeptide of the vaccinia virus DNA polymerase will require accessory protein(s) to form a stable enzyme-template interaction and direct processive DNA synthesis under isotonic conditions in vivo. PMID- 7983063 TI - Purification and characterization of phosphatidylcholine phospholipase D from pig lung. AB - Phospholipase D, which mediates phosphatidylcholine hydrolysis in response to agonist stimulation, is an important component of signal transduction. We now report the purification of this enzyme to homogeneity from pig lung microsomes. The enzyme was solubilized with heptylthioglucoside and purified 2,200-fold by successive chromatography on sulfate-Cellulofine, ether-Toyopearl, chelate Toyopearl, Q-Sepharose, heparin-Toyopearl, and hydroxyapatite. The final enzyme preparation gave a single protein band of M(r) = 190,000 on SDS-polyacrylamide gel electrophoresis. The enzyme hydrolyzed phosphatidylcholine but not lysophosphatidylcholine, phosphatidylethanolamine, and phosphatidylinositol. Optimum pH was 6.6. Half-maximal activity was obtained at 0.8 mM dipalmitoylglycerophosphocholine. The products were identified as phosphatidic acid and choline, but in the presence of ethanol, phosphatidylethanol was produced at the expense of phosphatidic acid. Ethanolamine and serine were not utilized as the phosphatidyl acceptor. Although not obligatory, Ca2+ and Mg2+ were stimulatory at high concentrations. The enzyme was markedly stimulated by unsaturated fatty acids in the presence of Mg2+ but not in its absence or by saturated fatty acids. N-Ethylmaleimide and detergents were inhibitory. Sucrose monolaurate had an aberrant effect on enzyme activity. PMID- 7983064 TI - Posttranslational regulation of plakoglobin expression. Influence of the desmosomal cadherins on plakoglobin metabolic stability. AB - Desmosomes are adhesive intercellular junctions that act as cell surface attachment sites for intermediate filaments. The desmosomal glycoproteins, desmogleins and desmocollins, are members of the cadherin family of adhesion molecules. In addition, desmoglein has been shown to coimmunoprecipitate with the junctional protein plakoglobin. To characterize further the interaction between plakoglobin and the desmosomal cadherins, stable mouse fibroblast (L-cells) cell lines were generated that express plakoglobin, desmoglein and plakoglobin, or desmocollin and plakoglobin. L-cell lines transfected with a plasmid encoding human plakoglobin expressed plakoglobin mRNA but very little plakoglobin protein. However, plakoglobin protein was expressed at high levels in L-cells coexpressing either desmoglein or desmocollin. In addition, both desmocollin and desmoglein were found to coimmunoprecipitate with plakoglobin. The transient expression of desmoglein in L-cell lines expressing plakoglobin mRNA resulted in the formation of a complex between plakoglobin and desmoglein and in the accumulation of plakoglobin protein. Furthermore, the rate of plakoglobin protein degradation was decreased by 15-20-fold in cell lines expressing either desmoglein or desmocollin. These results demonstrate that the desmosomal cadherins posttranslationally regulate plakoglobin expression by decreasing the rate of plakoglobin degradation. PMID- 7983065 TI - Interactions between collagen-binding stress protein HSP47 and collagen. Analysis of kinetic parameters by surface plasmon resonance biosensor. AB - A 47-kDa heat shock protein (HSP47) is a collagen-binding stress protein which is localized in the endoplasmic reticulum (ER) of collagen-secreting cells. Recent studies have shown that HSP47 transiently binds to newly synthesized procollagens and that conformationally abnormal procollagen is also bound by HSP47 for a much longer time in the ER (Nakai, A., Satoh, M., Hirayoshi, K., and Nagata, K. (1992) J. Cell Biol. 117, 903-914). HSP47 is thus suggested to have a collagen-specific molecular chaperone-like function. In this report, we analyzed the interaction of HSP47 and types I to V collagen using BIAcore system, an optical biosensor based on the principles of surface plasmon resonance. Types I-V collagen were purified from porcine skin, porcine articular cartilage, bovine lens capsule, and porcine placenta and immobilized on sensorchips of the BIAcore system at a surface concentration of 10-15 ng/mm2. Purified recombinant mouse HSP47 (rmHSP47) expressed in Escherichia coli was passed over the sensorchips at a flow rate of 2 microliters/min and binding curves of rmHSP47 to collagens were monitored. Using this approach, accurate association and dissociation rate constants were determined in addition to dissociation constants. rmHSP47 was found to bind to types I-V collagen with similar dissociation constants of the order of 10(-7) M. This relatively low dissociation constant resulted from the rapid dissociation rate constant (kdiss > 10(-2) s-1) and considerably high (kass approximately 2 x 10(4) M-1 s-1) association rate constant. These kinetic parameters may reflect a transient interaction between HSP47 and procollagen in vivo. PMID- 7983066 TI - Stimulation of phosphatidylinositol 3'-kinase association with foca adhesion kinase by platelet-derived growth factor. AB - We have previously described the stable association of the focal adhesion kinase (FAK) with phosphatidylinositol 3'-kinase (PI3K) in NIH 3T3 cells. This interaction was stimulated by cell adhesion in vivo and by autophosphorylation of recombinant FAK in vitro. In this report, we show that platelet-derived growth factor (PDGF) could also specifically stimulate this association in vivo. This stimulation is independent of cell adhesion or the integrity of the cytoskeleton, suggesting potentially different mechanisms by which the cell surface PDGF receptor and integrins regulate PI3K:FAK associations. We also found that this increased association in response to PDGF occurred in the membrane fractions, consistent with the recruitment of PI3K to the cell surface by the activated PDGF receptor. These results provide a novel mechanism of cross-talk between the signaling pathways initiated by PDGF and that initiated by integrins and raise the intriguing possibility that FAK might participate in some of the cellular effects of the growth factors in modulating cell morphology and migration. PMID- 7983067 TI - Activation of the mitogen-activated protein kinase signaling pathway in neutrophils. Role of oxidants. AB - In addition to their role in bacterial killing, reactive oxygen intermediates (ROI) produced by the NADPH oxidase may participate in the regulation of intracellular pathways. We have recently demonstrated that ROI produced by the oxidase regulate tyrosine phosphorylation in neutrophils, possibly by alterations in the cellular redox state. The purpose of the present study was to characterize the identities of certain of the redox-sensitive tyrosine-phosphorylated substrates and the significance of the increased phosphorylation. As a prominent 42-44-kDa phosphorylated band was noted in oxidant-treated cells, we investigated the possible phosphorylation and activation of mitogen-activated protein (MAP) kinase under these conditions. Immunoprecipitation of MAP kinase followed by immunoblotting with anti-phosphotyrosine antibodies indicated that a 42-44-kDa polypeptide was tyrosine-phosphorylated in response to treatment of cells, either with the oxidizing agent diamide or with H2O2 in cells where catalase was inhibited. Using an in vitro renaturation assay with myelin basic protein as the substrate, oxidant-induced stimulation of kinase activity of a 42-44-kDa band was observed in both whole cell extracts and in MAP kinase immunoprecipitates. The mechanism of redox-sensitive activation of MAP kinase was examined. First, exposure of cells to oxidants caused a significant increase in the activity of MEK (the putative activator of MAP kinase), as determined by an in vitro kinase assay using recombinant catalytically inactive glutathione S-transferase-MAP kinase as the substrate. Additionally, oxidant treatment of cells resulted in inhibition of the activity of CD45, a protein tyrosine phosphatase known to dephosphorylate and inactivate MAP kinase. We conclude that oxidant treatment of neutrophils can activate MAP kinase by stimulating its tyrosine and (presumably) threonine phosphorylation via MEK activation, a response that may be potentiated by inhibition of MAP kinase dephosphorylation by phosphatases such as CD45. PMID- 7983068 TI - Regulation of human type II phosphatidylinositol kinase activity by epidermal growth factor-dependent phosphorylation and receptor association. AB - Epidermal growth factor (EGF) stimulates phosphatidylinositol PtdIns) hydrolysis in many cell types by effecting the specific interaction between the EGF receptor and phospholipase C gamma. Several studies have suggested that PtdIns 4-kinase activity can also be regulated by EGF, but the mechanism of this stimulation was unclear. We report here that EGF treatment of intact A431 cells increased the association of type II PtdIns kinase with the EGF receptor within 1 min at 37 degrees C. Phosphorylation of immunoprecipitated EGF receptor also increased the association of PtdIns 4-kinase. Furthermore dephosphorylation of phosphoserine residues on the stimulated receptor immune complex led to inactivation of the bound PtdIns 4-kinase, while dephosphorylation of phosphotyrosine residues led to activation. Unlike the stimulated activity measured in total cell and plasma membrane lysates, the changes in activity of the immunoprecipitates were apparent at high substrate concentration. Metabolic labeling was used to show that a 55 kDa phosphoserine and phosphotyrosine-containing protein comigrated with renatured PtdIns 4-kinase activity on SDS-polyacrylamide gel electrophoresis, while in vitro labeling revealed only serine phosphorylation. These data are discussed with reference to the direct regulation of PtdIns 4-kinase by phosphorylation, PtdIns compartmentalization, and the formation of a multienzyme signal transduction complex. PMID- 7983069 TI - Neuroectodermal tumors expressing c-, L-, and N-myc in transgenic mice that carry the E1A/E1B gene of human adenovirus type 12. AB - Adenovirus early 1 (E1) region gene products, including E1A and E1B, are required for transformation of primary cultured rodent cells. In order to investigate in vivo action of the E1 region, we established a line of transgenic mice carrying the oncogenic E1A and E1B genes of human adenovirus type 12 under control of the human angiotensinogen promoter. Histopathological analyses indicated that transgenic mice heritably develop neuroectodermal tumors arising from the pelvic region with varying degrees of incidence. The transgene was expressed in the neuroectodermal tumors as well as in TNT-1 cells, a cell line established from the tumors, where the human angiotensinogen promoter was constitutively active. The high level expression of c-, L-, and N-myc without gene amplification was notable in the original tumors and TNT-1 cells, but not in another tissue examined. The co-expression of the three sets of myc family genes in both the original tumors and the established cell line provided the possibility that the target cells for transformation may belong to a specific cell type that expresses all these oncogenes during development. PMID- 7983070 TI - Subcellular localization and targeting of cathepsin E. AB - The subcellular distribution and targeting of the non-lysosomal aspartic proteinase cathepsin E have been studied using mouse L cells and monkey Cos 1 cells that were transfected with cDNA encoding cathepsin E. The cathepsin E was retained in L cells for at least 20 h without significant degradation and its single N-linked oligosaccharide remained sensitive to endo-beta-N-acetyl glucosaminidase H. When cathepsin E was overexpressed by transient transfection in Cos 1 cells, it was very slowly secreted into the media. The intracellular form of the enzyme contained a high mannose oligosaccharide which was processed to a complex type species upon secretion. In double label immunofluorescence studies, cathepsin E co-localized with cathepsin D-myc-KDEL, an endoplasmic reticulum (ER) marker. Subcellular fractionation on a Percoll density gradient showed that the cathepsin E co-migrated with membranous vesicles that were distinct from dense lysosomes. Only a trace amount of the enzyme was recovered in the soluble fraction. These findings indicate that in L cells and Cos 1 cells, the intracellular location of cathepsin E is the endoplasmic reticulum. To identify the protein sequences required for ER retention, we made chimeric proteins between cathepsin E and pepsinogen, an aspartic proteinase that is rapidly secreted by Cos 1 cells. We found that amino acids 1-48 of cathepsin E are important for its retention in the ER. Within this region, Cys7, which is involved in covalent dimer formation, plays a significant role in the retention. PMID- 7983071 TI - A GTP-binding protein regulates the activity of (1-->3)-beta-glucan synthase, an enzyme directly involved in yeast cell wall morphogenesis. AB - Synthesis of (1-->3)-beta-D-glucan, the major structural component of the yeast cell wall, is synchronized with the budding cycle. Membrane-bound, GTP-stimulated (1-->3)-beta-glucan synthase was dissociated by stepwise treatment with salt and detergents into two soluble fractions, A and B, both required for activity. Fraction A was purified about 800-fold by chromatography on Mono Q and Sephacryl S-300 columns. During purification, GTP binding to protein correlated with synthase complementing activity. A 20-kDa GTP-binding protein was identified by photolabeling in the purified preparation. This preparation no longer required GTP for activity, but incubation with another fraction from the Mono Q column (A1) led to hydrolysis of bound GTP to GDP with a concomitant return of the GTP requirement. Thus, fraction A1 appears to contain a GTPase-activating protein. These results show that the GTP-binding protein not only regulates glucan synthase activity but can be regulated in turn, constituting a potential link between cell cycle controls and wall morphogenesis. PMID- 7983072 TI - In vivo regulation of the mouse beta myosin heavy chain gene. AB - The interactions of trans-acting factors with their respective cis-acting elements in the 5' upstream region of the beta myosin heavy chain gene (MyHC) regulate its tissue- and developmental stage-specific expression. The role of three conserved elements, an MCAT or TEF-1 binding site, a C-rich region, and a beta e3 region, in muscle-specific gene expression was analyzed in vivo. Each cis acting site was ablated in the context of the beta MyHC promoter, fused to the chloramphenicol acetyltransferase reporter gene, and used to generate transgenic mice. In contrast to results obtained in vitro, the data demonstrate that mutating any one of these cis-acting elements does not affect the level or tissue specificity of transgene expression. Sequences upstream of -600 can functionally substitute for any one of these regulatory cassettes and are important both for high levels of expression as well as for controlled muscle specificity. Mutation of any two of the cis-acting elements also does not affect transgene expression. However, simultaneous mutation of the three sites significantly reduces expression, indicating that these conserved sequences do play an important role and that combinatorial interactions underlie the beta MyHC's regulation. PMID- 7983073 TI - The upstream region is required but not sufficient to control mutually exclusive expression of Paramecium surface antigen genes. AB - Paramecium tetraurelia stock 51 can express at least 11 different surface antigens, yet only one type is found on the surface of a cell at any given time. The mechanism that controls this mutually exclusive expression is unknown. A previous study has shown that the 51A surface antigen gene is regulated at the level of transcription (Gilley, D., Rudman, B. M., Preer, J. R., Jr., and Polisky, B. (1990) Mol. Cell. Biol. 10, 1538-1544). We show here that the 51B surface antigen gene is also transcriptionally regulated, and when the 51A and 51B genes are cotransformed into an A-, B- mutant, the 51A antigen is dominant at 27 degrees C just as in wild type cells. We have utilized this cotransformation system to experimentally determine that 273 base pairs of DNA upstream of the 51A gene is sufficient to allow the dominant expression of A, but 150 base pairs is not adequate. A hybrid gene that contains the upstream region of 51B attached to the 51A transcribed region was cotransformed with the 51B gene into the A-, B- mutant. Despite containing the same upstream sequences, only the hybrid 51B/A was transcribed at 27 degrees C. These results suggest the upstream region is required but not sufficient for mutually exclusive transcriptional control. PMID- 7983074 TI - Identification and immunological characterization of the domain of Actinobacillus actinomycetemcomitans leukotoxin that determines its specificity for human target cells. AB - Although extensive amino acid homology exists among the various Repeats in ToXin (RTX) family of bacterial cytolysins, the cellular and species specificities remain unique for individual toxins (i.e. Actinobacillus actinomycetemcomitans leukotoxin (LtxA) kills human monomyelocytes while a related toxin, Pasteurella hemeolytica leukotoxin (LktA) kills bovine lymphoid cells). To determine the Ltx domain responsible for species specificity, ltxA/lktA chimeric toxin genes were expressed in tandem with the ltxC gene under control of the P lambda promoter. The ability of lysates to kill either HL-60 (human) or BL-3 (bovine) cells was assessed by trypan blue exclusion. The critical area required for the chimeric toxins to recognize human target cells is a 253-amino acid fragment (residue 688 941) that contains the GGXGXDX(L[I[V[W[Y[F)X repeats. A panel of 12 neutralizing anti-LtxA monoclonal antibodies also recognized specificities within the 253 amino acid fragment. Epitope mapping of the monoclonal antibody panel showed that all antibodies bound to one of three sites on the LtxA molecule. One monoclonal recognized epitope A which was composed of LtxA residues 698-709 (KLDYYYTNKGFK), six antibodies recognized epitope B, a peptide composed of residues 746-757 (LIYGYDGDDRLY), whereas the remaining five monoclonals recognized epitope C, which is composed of residues 926-937 (DRARLKRQFELQ). PMID- 7983075 TI - The far upstream chicken lysozyme enhancer at -6.1 kilobase, by interacting with NF-M, mediates lipopolysaccharide-induced expression of the chicken lysozyme gene in chicken myelomonocytic cells. AB - Macrophages respond to lipopolysaccharide (LPS) with the activation of various genes, including the lysozyme gene. Here, we show that the level of lysozyme mRNA increases following treatment of chicken myelomonocytic HD11 cells with LPS. By transient and stable transfection of the chloramphenicol acetyltransferase (CAT) gene controlled by regulatory elements of the lysozyme gene, we identified a subfragment of the -6.1 kilobase (kb) lysozyme enhancer that mediates the LPS induced lysozyme expression. This subfragment contains two elements (D and E), each of which matches the highly degenerate consensus sequence of binding sites for C/EBP-like transcription factors. Furthermore, we found protein complexes to interact with elements D and E whose binding activity to elements D and E is LPS inducible in myelomonocytic HD11 cells. Immunomobility shift assays show that NF M, a myeloid-specific C/EBP beta-related transcription factor is an essential component of these protein complexes. Mutations of the C/EBP binding sites within D and E cause a reduction of basal activity and abolish LPS responsiveness of the -6.1 kb lysozyme enhancer. These results show that the -6.1 kb lysozyme enhancer, in addition to its role in cell type-specific expression, can mediate, by interacting with NF-M, LPS-induced expression of the lysozyme gene in chicken myelomonocytic cells. PMID- 7983076 TI - Purification and characterization of transmembrane forms of heparin-binding EGF like growth factor. AB - Heparin-binding epidermal growth factor-like growth factor (HB-EGF), whose cDNA has a predicted 208-codon open reading frame, is synthesized as a membrane spanning precursor that is processed to release mature mitogenic proteins of approximately 73-87 amino acids in length. Previous work has focused on the structural and biological properties of secreted HB-EGF. In this study, human recombinant transmembrane HB-EGF, produced by expression of HB-EGF1-208 cDNA in a baculovirus system, has been isolated, purified, and characterized structurally and biologically. Two isoforms of transmembrane HB-EGF (HB-EGFTM) were purified from membrane fractions of infected insect cells by a combination of heparin affinity chromatography and reversed-phase high performance liquid chromatography. The isoform designated as HB-EGFTM-1, a 21.5-kDa protein, yielded no N-terminal sequence, suggesting that it is N-terminally blocked. However, HB EGFTM-II, a 24-kDa protein, was N-terminally sequenced and found to be initiated at Asp63 in the 208-amino acid residue primary translation product. This N terminus is the same as that determined for a 18-kDa isoform of secreted HB-EGF purified from the conditioned medium of insect cells expressing HB-EGF1-149 cDNA and is also identical to the N terminus of the longest form of secreted HB-EGF initially purified from human macrophage-like U-937 cell conditioned medium. HB EGFTM-II cross-reacted on a Western blot with an antibody directed against the 16 C-terminal amino acids of the cytoplasmic tail of HB-EGF, indicating that it contains a putative transmembrane domain. HB-EGFTM-II was bioactive and stimulated the proliferation of BALB/c 3T3 cells and smooth muscle cells and the motility of smooth muscle cells, albeit with approximately 10-25% of the specific activity of secreted HB-EGF isoforms. We concluded that transmembrane HB-EGF is bioactive when isolated, consistent with the possibility of its functioning as a juxtacrine growth factor when still tethered to the cell. PMID- 7983077 TI - Complex alternative RNA splicing of epsilon-immunoglobulin transcripts produces mRNAs encoding four potential secreted protein isoforms. PMID- 7983078 TI - Effects of omega-conotoxin GVIA on electrical field stimulation- and agonist induced changes in cytosolic Ca2+ and tension in isolated rat anococcygeus muscle. AB - 1. It has been reported that omega-conotoxin GVIA (omega-CgTx) blocks L- and N type voltage-sensitive Ca2+ channels (VSCCs) in neurones and inhibits neurotransmitter release in various tissues. The present study investigates the effects of omega-CgTx on electrical field stimulation (EFS)- and agonist-induced changes in free cytosolic Ca2+ ([Ca2+]cyt) levels and tension in isolated fura-2 loaded rat anococcygeus muscle. 2. EFS produced frequency-dependent increases in [Ca+]cyt levels and contractions. Phentolamine (1 microM) and omega-CgTx (0.1 microM) significantly inhibited EFS-induced responses and shifted the frequency response curves to the right. 3. alpha-adrenoceptor agonists (noradrenaline and clonidine) and carbachol (in the presence of phentolamine) produced concentration dependent increases in [Ca2+]cyt levels and contractions. Though omega-CgTx (0.1 microM) significantly inhibited the increases in [Ca2+]cyt levels induced by low doses of noradrenaline, the overall concentration-response curves of [Ca2+]cyt and contractions for noradrenaline, clonidine, and carbachol were not affected by omega-CgTx. 4. When the tone of rat anococcygeus muscle was raised with either clonidine (0.1 microM) or carbachol (30 microM, in the presence of 3 microM phentolamine), EFS (2 Hz) produced reproducible decreases in [Ca2+]cyt levels and relaxations. These responses were significantly inhibited by omega-CgTx when the tissue was precontracted with clonidine, but not when it was precontracted with carbachol. 5. The results of the present study suggest that in rat anococcygeus muscle, omega-CgTx inhibits the EFS-induced release of both excitatory and inhibitory neurotransmitters, probably by blocking Ca2+ channels on nerve terminals. Furthermore, the Ca2+ channels present on the smooth muscle cell membrane, which are involved in the agonist-induced Ca2+ influx and contractions, may not be sensitive to omega-CgTx. PMID- 7983079 TI - Atrial natriuretic factor modifies noradrenaline release in a sodium-free medium. AB - 1. The effects of atrial natriuretic factor (ANF) on 3H-noradrenaline (3H-NA) release evoked by a sodium-free medium (SFM) were studied. The experiments were carried out in rat hypothalamic slices incubated in vitro. 2. ANF (1, 10 and 100 nM) decreased NA release evoked by the omission of sodium in a concentration dependent way. When calcium was omitted from a SFM, NA output was partially diminished. However, if ANF was added to the SFM/calcium free medium NA secretion showed no modifications. 3. Present results suggest that, in rat hypothalamus, NA release evoked by Na+ omission is divided into two fractions: one independent of and the other dependent on extracellular calcium. In addition, ANF modifies NA release evoked by SFM dependent on extracellular calcium. PMID- 7983080 TI - Muscarinic M3 receptors mediate contractions in rabbit, endothelium-denuded aorta in vitro. AB - 1. Muscarinic receptors mediating contraction of rabbit endothelium-denuded aorta have been characterized functionally, in vitro, using a range of antagonists (atropine, pirenzepine, methoctramine, himbacine, 4-diphenyl-acetoxy-N-methyl piperidine methiodide (4-DAMP) and para-fluoro-hexahydro-siladifenidol (p-F HHSiD). 2. The non-selective muscarinic agonist, (+)cis-dioxolane, induced concentration-dependent contractions of endothelium-denuded aortic rings. The potency (EC50) of (+)cis-dioxolane was 1.0 +/- 0.4 microM and the maximal increase in isometric tension was 944 +/- 98 mg (mean +/- SEM, n = 25). The concentration-effect curves to (+)cis-dioxolane were shifted to the right in the presence of antagonists, in a concentration-dependent manner. The following affinities (-log KB) were calculated; atropine, 9.4; pirenzepine, 6.6; methoctramine, 5.9; himbacine, 7.1; 4-DAMP, 9.2; and p-F-HHSiD, 7.7. 3. It is concluded that muscarinic M3 receptors mediate contractions of endothelium denuded aorta. The low potency of (+)cis-dioxolane, when compared to its potency in other M3 receptor assays, suggests that the efficiency of receptor coupling, associated with contraction of this tissue, is poor. PMID- 7983081 TI - Renal D1 receptors, and not D2, are upregulated after aortic constriction and may be involved in cardiac hypertrophy. AB - 1. The characteristics of dopamine (D) receptors were studied in kidney using the radiolabelled receptor assay of [3H]-SCH-23390 for D1 and [3H]-sulpiride for D2 receptors during cardiac hypertrophy. Male Sprague-Dawley rats (175-200 g) underwent abdominal aortic constriction above the renal arteries and were studied 28 days thereafter. Sham operated animals without aortic constriction were used as control. 2. Membranes obtained from kidney cortex showed an increase in the number of binding sites (Bmax) of D1 receptors in the aortic banded group. The apparent affinity for the ligand (Kd) was unchanged with D1 receptors, as compared to sham control. Both Bmax and Kd were unchanged for D2 receptors in the aortic banded group. 3. Autoradiographic data further reinforced the findings, showing an increased number of D1 receptors in the kidney at 28 days after abdominal aortic constriction. These changes were associated with an increase in plasma renin activity in the aortic banded group. Further, Na(+)-K(+)-ATPase as measured by fmol of 32Pi released from [gamma-32P]-ATP, was decreased in the kidney cortex of banded animals. 4. Reversal of hypertrophic parameters was observed in the aortic banded group treated for 14 days with SCH 23390 hydrochloride (0.1 mg kg-1 i.p.), a known D1 receptor antagonist. 5. The present study shows an upregulation of renal D1 receptors following abdominal aortic constriction and it is suggested that upregulation of D receptors may be involved in the development of cardiac hypertrophy. PMID- 7983082 TI - In vitro chondrocyte collagen deposition within porous HDPE: substrate microstructure and wettability effects. AB - The effects of microstructure and wettability of porous high density polyethylene (HDPE) substrates on chondrocyte collagen synthesis in vitro were assayed. Three size grades of hydrophilic and hydrophobic HDPE substrates with ranges of pore volumes of 40-60%, pore sizes of 115-335 microns, and surface areas per unit volumes of 7-20 mm2/mm3 were seeded with fetal bovine chondrocytes. After 7 days of incubation, the cells within all substrates remained spherical, and contained mainly type II collagen (as verified by type I and II collagen I-ELISAs). After 21 days, the majority of cells had spread; however, the matrices still contained mainly type II collagen. The hydrophilic matrices contained significantly more type II collagen than the hydrophobic matrices at both 7 and 21 days, whereas the amount of type II collagen was not influenced by the pore attributes. A significantly higher percentage of type II collagen was also observed in all seeded porous substrates as compared with seeded polystyrene culture dishes, perhaps indicating that the three-dimensional particular nature of the HDPE matrices enhanced the maintenance of phenotypically differentiated chondrocytes and entrapment of their extracellular matrix products. PMID- 7983083 TI - The effects of ultrasound irradiation on a biodegradable 50-50% copolymer of polylactic and polyglycolic acids. AB - The aim of this study was to investigate the effects of ultrasound irradiation on a biodegradable drug delivery system. Microporous, disk-shaped specimens of a 50 50% copolymer of polylactic and polyglycolic acids were gel cast from an acetone solution. A protein was incorporated in these specimens, which were then immersed in phosphate buffered saline and subjected to ultrasound irradiation every second day. The investigation was performed in two phases: in the first, a study was performed for 58 days to determine if ultrasonic irradiation affected the kinetics of protein release from the specimens. In the second phase, effects of frequency and duration of the ultrasound signal on the degradation of the implant were studied for 40 days. The results indicate that ultrasound irradiation resulted in almost a threefold increase in protein elution from the specimens. Both the ultrasound frequency and signal duration affected the molecular weight loss and mass loss, and changed the overall degradation kinetics of the polymer. PMID- 7983084 TI - Resistance of hyaluronate coatings to hyaluronidase. AB - Mucopolysaccharides such as hyaluronic acid and its salts are essential components of new hydrophilic bilaminar coatings being developed in these laboratories. The polysaccharide top-coat is covalently bonded by periodic urethane links to a substrate copolymer which in this study has been coated on polymethyl methacrylate slabs. Such coated slabs were exposed for up to 28 months to three levels of hyaluronidase in phosphate buffered saline at 37 degrees C, the enzyme concentration ranging from that normally present in human serum to 60 times that level. The coating survived without damage. The rationale proposed is that the enzyme is unable to position its active site with the immobilized hyaluronate molecule and is therefore unable to catalyze the hydrolysis. PMID- 7983085 TI - The effect of additive hyaluronic acid on animal joints with experimentally reduced lubricating ability. AB - A series of in vitro experiments demonstrated a clear effect of additive hyaluronic acid (HA) on animal joints with experimentally reduced lubricating ability. Eleven canine hip joints were utilized and the experimental conditions tested were: i) intact joints, ii) after washing the joint surfaces, and iii) after adding 1% HA to them. The frictional coefficient of every joint increased after washing and subsequently decreased after adding HA. The mean values were 0.007 (SD 0.004) on the intact joints, 0.020 (SD 0.009) after washing, and 0.013 (SD 0.005) after the addition of HA. The differences between the three values of frictional coefficients were shown to be statistically significant (p < 0.01). PMID- 7983086 TI - In vitro plasma protein adsorption and kallikrein formation on 3 mercaptopropionic acid, L-cysteine and glutathione immobilized onto gold. AB - 3-Mercaptopropionic acid (MPA), L-cysteine (L-cys), and glutathione (GSH) monolayers were immobilized onto gold and used in in vitro protein tests. The surfaces were characterized with ellipsometry, static contact angle measurements, atomic force microscopy, and Fourier transform infrared reflection absorption spectroscopy (FT-IRAS). After incubations in human plasma and antibody solutions, the surface antisera binding patterns were determined with ellipsometry. Using serum instead of plasma, complement activation was studied in the same fashion. Activated coagulation Factor XII and kallikrein formation on the surfaces and in the plasma were studied using a kallikrein-specific colorimetric assay. 3 Mercaptopropionic acid indicated contact activation of coagulation but L-cysteine did not. Glutathione displayed low deposition of plasma proteins, large deposition of proteins from serum, and did not promote kallikrein formation. None of the surfaces could be attributed complement activating properties, as determined by antibody deposition. The present study demonstrates that surface biology in complex model systems can be conveniently studied in vitro through systematic and well defined surface modifications. PMID- 7983087 TI - Joint resurfacing using allograft chondrocytes and synthetic biodegradable polymer scaffolds. AB - Cartilage implants which could potentially be used to resurface damaged joints were created using rabbit articular chondrocytes and synthetic, biodegradable polymer scaffolds. Cells were serially passaged and then cultured in vitro on fibrous polyglycolic acid (PGA) scaffolds. Cell-PGA constructs were implanted in vivo as allografts to repair 3-mm diameter, full thickness defects in the knee joints of adult rabbits, and cartilage repair was assessed histologically over 6 months. In vitro, chondrocytes proliferated on PGA and regenerated cartilaginous matrix. Collagen and glycosaminoglycan (GAG) represented 20 to 8% of the implant dry weight (dw), respectively, at the time of in vivo implantation; the remainder was PGA and unspecified components. Implants based on passaged chondrocytes had 1.7-times as much GAG and 2.6-times as much collagen as those based on primary chondrocytes. In vivo, cartilaginous repair tissue was observed after implantation of PGA both with and without cultured chondrocytes. Six month repair was qualitatively better for cell-PGA allografts than for PGA alone, with respect to: 1) surface smoothness, 2) columnar alignment of chondrocytes, 3) spatially uniform GAG distribution, 4) reconstitution of the subchondral plate, and 5) bonding of the repair tissue to the underlying bone. These pilot studies demonstrate that it is feasible to use cell-polymer allografts for joint resurfacing in vivo. PMID- 7983088 TI - Magnetically directed poly(lactic acid) 90Y-microspheres: novel agents for targeted intracavitary radiotherapy. AB - High energy beta-emitting radioisotopes like Yttrium-90 have a radiotoxic range of about one centimeter. For cancer treatment they must be brought near the tumor cells and kept there for as long as they are radioactive. We developed as carriers for the ionic form of 90Y a matrix-type polymeric drug delivery system, poly(lactic acid) (PLA) microspheres. This radiopharmaceutical could be selectively delivered to the target site after incorporating 10% Fe3O4 (magnetite) which made the magnetic microspheres (MMS) responsive to an external magnetic field. Furthermore, MMS are biodegradable and slowly hydrolyze into physiologic lactic acid after the radioactivity is completely decayed. Previously prepared 10-40 microns MMS were radiochemically loaded to high specific activity with 90Y at a pH of 5.7. Stability studies showed that approximately 95% of added 90Y is retained within the PLA matrix after 28 days (> 10 half-lives) at 37 degrees C in serum, and electron microscopy showed that the microspheres retained their characteristic morphologic appearance for the same time period. Cytotoxicity studies with SK-N-SH neuroblastoma cells growing in monolayer showed that the radiocytotoxicity of the microspheres could be directed magnetically to either kill or spare specific cell populations, thus making them of great interest for targeted intracavitary tumor therapy. We are currently optimizing this system for use in the treatment of neoplastic meningitis. PMID- 7983089 TI - Calcium phosphate plasma-sprayed coatings and their stability: an in vivo study. AB - Several factors playing a possible role in determining coating stability and bone tissue response were studied in in vivo experiments. These factors involving the plasmaspray coating procedure were as follows: 1) plasmaspray powder port 2 or 6; 2) particle size distribution; 3) hydroxylapatite versus fluorapatite coatings; and 4) the effect of post-heat treatment. Coating stability and bone tissue response were examined by measuring coating thickness, coating length, and bone apposition against the coatings. The result was that heat treatment influenced coating stability significantly. Also, bone formation was more intense. Fluorapatite proved to be more stable than hydroxylapatite, which was in agreement with our previous reports. PMID- 7983090 TI - Evaluation of a series of tyrosine-derived polycarbonates as degradable biomaterials. AB - A series of four polycarbonates derived from the ethyl, butyl, hexyl, and octyl esters of desaminotyrosyl-tyrosine was prepared by condensation polymerization. The resulting polymers had weight average molecular weights ranging from 120,000 450,000, and their chemical structure was confirmed by elemental analysis, nuclear magnetic resonance, and Fourier transform infrared spectroscopy. The polycarbonates were evaluated as degradable biomaterials. Their surface properties were determined by electron spectroscopy for chemical analysis, attenuated total reflectance-Fourier transformed infrared spectroscopy, and contact angle measurement. The degree of surface hydrophobicity was related to the length of the alkyl ester pendent chain. The tensile properties were dependent on the chemical structure of the polymers: For thin, solvent cast film specimens, the tensile modulus varied from 1.2-1.6 GPa, and the strength at break from 60-220 MPa. The degradation of polymeric films was followed in vitro by measuring changes in mechanical strength for up to 40 weeks, and the decrease in molecular weight and changes in surface chemistry for up to 80 weeks. The length of the pendent chain affected the degradation behavior and strength retention; the polymers with short pendent chains were more readily hydrolyzable. For sterilization, ethylene oxide treatment was less destructive, as judged by molecular weight retention, than gamma-irradiation. Spin-cast films of all tested polycarbonates were not cytotoxic toward cultured rat lung fibroblasts. The cell response was influenced by the chemical structure of the polymer. The least hydrophobic polycarbonate (having a short ethyl ester pendent chain) was a more stimulating substrate for cell growth than the more hydrophobic polymers (carrying longer alkyl ester pendent chains). PMID- 7983091 TI - The acoustic properties of normal and imbedded bovine bone as measured by acoustic microscopy. AB - The acoustic impedance of bovine femoral cortical bone was measured with a scanning acoustic microscope used in the reflection mode. The bone was measured in the unimbedded state and after plastic imbedding. The acoustic impedance of the unimbedded specimens was also measured with a standard transmission ultrasonic technique. For the unimbedded bovine specimens there was a good correlation between the bulk transmission impedance and the reflection surface impedance (r2 = 0.976) and the values were 9.32 and 9.29 MRayls, respectively. Plastic imbedding produced a consistent and statistically significant increase in the acoustic impedance of the bone (9.71 MRayls). This experiment verified the use of acoustic microscopy as a quantitative materials analysis technique and it demonstrated the potential for material property analysis of imbedded bone. PMID- 7983092 TI - Characterizations of titanium implant surfaces. III. AB - There are several reports in the literature concerning the similarities and the differences between the oxide on cpTi and Ti-6A1-4V alloy; however, their biological sequelae are not entirely known. In this work, a series of surface characterization techniques were used in conjunction with short term in vitro biological assays to assess the effects of materials selection (cpTi and Ti alloy) on osteoblast-like cell responses. Surface analysis indicated that with the exception of oxide thickness, there were no significant differences in surface characteristics between the two implant materials. These results were reflected in the biological studies, where the levels of cell attachment and adaptation of the attached cells to the titanium surfaces were similar. These results are in general agreement with previous in vivo studies and continue to indicate that cpTi and Ti alloy are suitable, biologically compatible materials for fabrication of dental implants. PMID- 7983093 TI - Numerical analysis of extracellular fluid flow and chemical species transport around and within porous bioactive glass. AB - Modeling of the physical phenomena present at the biomaterial-tissue interface provides a valuable tool for examining the underlying mechanisms which influence the overall behavior of the implant-host system. Based on histological data from a previous implantation study (E. Schepers, M. De Clercq, P. Ducheyne, and R. Kempeneers, "Bioactive glass particulate materials as a filler for bone lesions," J. Oral Rehab.; 18, 439-452, 1991, Ref. 1) which documented the differentiation of mesenchymal cells to cells expressing the osteoblastic phenotype in porous bioactive glass, a finite element momentum and mass transport model was constructed. In this analysis, the extracellular compositional variations and fluid flow conditions around and within porous bioactive glass granules were determined. Numerical simulations demonstrated that the interstitial fluid flow around these granules (300-360 microns) is viscosity dominated (low Reynolds number flow) and that the fluid inside the granules remains stagnant. This velocity field results in shear stresses proportional to the velocity gradient at the granule-fluid interface outside the particles and no shear stresses inside the particles. A parametric study on the effect of interstitial fluid flow on chemical species (Na+, Ca+2, HPO(4)-2) transport outside the granules revealed three domains. At low velocities (0-0.1 micron/s), the transport of species is diffusion controlled. At intermediate velocities (1.0-10 microns/s), diffusion and convection contribute to the species transport. The concentration of chemical species is nearly uniform at high velocities (100-800 microns/s). For all three cases, the transport of chemical species within the granules is diffusion controlled. The differences in transport mechanisms and interstitial fluid flow conditions lead to variations in concentrations, reaction rates, and shear stresses between the inside and the outside of the glass granules. These differences may influence cellular migration, attachment, differentiation, and the overall response to these bioactive materials. PMID- 7983094 TI - Features of calcium phosphate plasma-sprayed coatings: an in vitro study. AB - Factors involved with the plasma-spray coating procedure, such as starting powder compound (fluorapatite, hydroxylapatite, magnesium-whitlockite, or tetra-calcium phosphate), powder particle distribution 1-45 or 1-125 microns), powder port gun (port 2 or 6), and post-heat treatment of 1 h at 600 degrees C, were examined for their effects on crystallinity and solubility/stability of the coating. From solubility tests, X-ray diffractometry, and scanning microscopy studies, the solubility and crystallinity were found to be dependent on Ca/P ratio, particle distribution, and post-heat treatment. The post-heat treatment influenced the degree of both crystallinity and solubility. The plasma-spray powder port factor for the hydroxylapatite coatings was not significant. Incubation in buffer of the coatings introduced precipitation at the surfaces of all non-heat-treated coatings except fluorapatite. No precipitation could be observed in any of the heat-treated coatings. PMID- 7983095 TI - Unintended pregnancy and sex education in Chile: a behavioural model. AB - This study analysed factors associated with unintended pregnancy among adolescent and young adult women in Santiago, Chile. Three variations of a behavioural model were developed. Logistic regression showed that the effect of sex education on unintended pregnancy works through the use of contraception. Other significant effects were found for variables reflecting socioeconomic status and a woman's acceptance of her sexuality. The results also suggested that labelling affects measurement of 'unintended' pregnancy. PMID- 7983096 TI - Assortative mating in a Spanish population: effects of social factors and cohabitation time. AB - Assortative mating for 22 anthropometric and body composition characteristics and social indicators was studied in a Spanish sample of 114 married couples. Significant spousal similarity was found for occupation, educational level and number of siblings. Sex-age adjusted spouse correlations were significant for stature, ileospinal height, total arm length, and biacromial breadth. Spouse correlations were not altered after allowance for socioeconomic effects. When couples were grouped according to marriage duration, differences in mate correlations for fatness were detected, suggesting a cohabitational effect on spouse resemblance. PMID- 7983097 TI - Some correlates of child mortality in the refugee populated regions in Tanzania. AB - Data from the 1988 Tanzania census were used to examine child mortality in three regions populated with Burundi refugees. Logistic and least squares analyses show that for both Tanzanian nationals and refugees low levels of maternal education are associated with high child mortality levels. Children born to mothers who are housewives are associated with low levels of mortality compared to those born to employed mothers, though the results were not statistically significant for the refugees. Maternal demographic status, computed from age and parity, has a strong effect on child survival. Unexpectedly, child mortality was lower where the water source was a well outside the village. Tanzanian mothers who are at highest risk of childbearing are roughly 6.4 times more likely to have a child death than those at lowest risk; the corresponding figure for the refugees is 36.8. This emphasises the need to intensify family planning programmes in these regions. PMID- 7983098 TI - Infant mortality in Nigeria: effects of place of birth, mother's education and region of residence. AB - This paper examines the effects of a child's place of birth, mother's education, region of residence and rural and urban residence on infant mortality in Nigeria between 1965 and 1979, using data from the 1981/82 Nigeria Fertility Survey. Infant mortality rates declined in all regions between 1965 and 1979. Children born in modern health facilities, irrespective of their mothers' place of residence, experienced significantly lower rates of infant mortality than those born elsewhere. Logistic regression analysis showed that all other variables tested were also significant, although some to a lesser degree. Efforts to reduce infant mortality in Nigeria should include policies that rectify rural and urban differentials in the distribution of health facilities and encourage their use. PMID- 7983099 TI - Ultradian behaviour cycles in a village community of Colombian Indians. AB - The daily activities observed in a Colombian village community of contemporary hunting and gathering people were analysed with respect to their time structure. Short term cycles of about 2 hours could be detected in both individual and common behavioural patterns. These behaviour cycles of individual group members appear to have been synchronised by social interaction. From temporal variations of individual activities a common ultradian time frame emerged. PMID- 7983100 TI - Religious affiliation and fertility in Liberia. AB - This study examines fertility differentials by religious affiliation in Liberia, within the context of two competing hypotheses: the characteristic and particularised theology. Using a subsample of currently married women from the 1986 Liberian Demographic and Health Survey, the study examines the fertility of five religious groups: Catholic, Protestant, Moslem, traditional, and other women. Overall, the findings are more consistent with the characteristic hypothesis, because the small fertility differentials by religious affiliation are largely accounted for by differences in the socioeconomic and demographic characteristics of these women. PMID- 7983101 TI - Age of mother at last birth in two historical populations. AB - This study uses sets of historical family reconstitutions from all of Quebec and from four villages of the Haut-Jura, France--first marriages of 2226 and 994 women, respectively--to investigate the physiological and social factors affecting age of mother at last birth before and during fertility transition. Age remained high throughout the period covered in Quebec, under 'natural' conditions, but showed a steady decline in the French material which extends to late 19th century generations practising family limitation. Age at marriage had no influence in Quebec; in France, however, women with the most surviving children at age 35 continued childbearing the latest. There was no link between biological ability to achieve a live birth, or in health status or aging rhythm, and age at last birth. Behaviour of mothers and daughters showed no relation. The variability in age at last birth thus appears to be random under natural conditions; with the onset of controls, social differences seem to influence not only the end of childbearing, but all aspects of behaviour governing final family size and child survival. PMID- 7983103 TI - Fertility decline in Tanzania. AB - According to the 1991/92 Tanzania Demographic and Health Survey, a Tanzanian woman has, on average, 6.1 births before she reaches age 50, a decline of about one birth per woman since the early 1980s. The major proximate determinant of fertility is universal and prolonged breast-feeding. An analysis of the social and demographic correlates of fertility shows that infant and child mortality, level of education and age at first marriage are among the factors which significantly influence fertility in Tanzania. PMID- 7983102 TI - Factors related to duration of postpartum amenorrhoea among USA women with prolonged lactation. AB - Duration of postpartum amenorrhoea (PPA) was compared among women who breast-fed for > or = 6 months (breast-feeding group) or < or = 3 months (formula-feeding group) and was found to be significantly shorter among the latter. Associations between maternal factors and duration of PPA were examined. Within the formula feeding group, the only variable associated with duration of PPA was duration of breast-feeding. Among breast-feeding mothers who resumed menstruation after 3 months postpartum, duration of PPA was positively associated with parity and negatively associated with maternal body mass index (BMI) at 3 months postpartum. Among breast-feeding mothers who resumed menstruation after 6 months, duration of PPA was positively associated with parity, pregnancy weight gain, number of night feeds and milk volume at 6 months, and negatively associated with maternal age and BMI at 6 months postpartum. These results indicate that maternal anthropometric status is related to duration of PPA, even in a relatively well nourished population of lactating women. PMID- 7983104 TI - Variability in behavioural risk factors for heart disease in an Australian aboriginal community. AB - The variability of three behavioural risk factors for heart disease--heavy alcohol and tobacco consumption and physical inactivity--was assessed in an Australian Aboriginal community, where heart disease death rates were high. Prevalence levels were assessed by comparison with those experienced by all adult Australians and by evaluating whether Aboriginal rates were influenced by underlying sociodemographic conditions. Relative risk ratios, odds ratios and logistic regression analysis were used. A total of 159 males and 114 females participated. Compared to all Australians, Aborigines are significantly more likely to drink five or more drinks on a drinking day, to be current smokers, and not to participate in vigorous exercise. In the Aboriginal community, univariate analysis indicates that: the odds of being a heavy drinker are significantly higher for those in unsatisfactory health; odds of being a current smoker are significantly higher for those in unsatisfactory health or unemployed; odds of not participating in vigorous exercise are significantly higher for those in unsatisfactory health, unemployed or without secondary education. Multivariate analysis shows unemployed or without secondary education. Multivariate analysis shows that risk of being a heavy drinker is independently associated with sex, age, and health status; risk of being a current smoker is associated with health and employment status. The risk of not participating in vigorous exercise is significantly related to all sociodemographic variables examined. Reasons for these associations are discussed. PMID- 7983106 TI - Recovery from low back injury. PMID- 7983105 TI - The impact of husband's and wife's education and occupation on family size in Zimbabwe. AB - This paper assesses the impact of husband's and wife's education and occupation on family size in Zimbabwe. Results from the 1988 Male Fertility Survey indicate that husband's education had a strong negative effect, and wife's education had a moderate negative effect on the number of children ever born. Contrary to the literature, wives who were not employed had significantly fewer children than those who work in agriculture, and fewer, but not significantly, than those in non-agricultural occupations. Findings show the importance of husband's education and the changing dynamics of wife's occupation in fertility decline. PMID- 7983107 TI - Bioactive ceramics. PMID- 7983108 TI - Early diagnosis of spinal tuberculosis by MRI. AB - MRI was performed at three centres in Bombay on 24 patients clinically suspected of tuberculosis of the spine but with normal radiographs. There were 11 males and 13 females and their average age was 24 years (11 to 60). 99mTc bone scans were done in 16 patients before MRI. Eleven patients had the diagnosis confirmed by biopsy and the remainder all responded rapidly to specific antituberculous chemotherapy. On T1-weighted images there was a decrease in signal intensity of the involved bone and soft tissues; on T2-weighted images there was increased signal intensity. Depending on the stage of the disease, three different patterns of infection were revealed: osteitis, osteitis with an abscess, and osteitis with or without an abscess plus discitis. The anatomical pattern of involvement, particularly of the soft tissues and the discs, is specific for tuberculous disease. The ability of MRI to detect tuberculosis of the spine earlier than other techniques could reduce bone destruction and deformity and diminish the need for surgical intervention. Despite the specificity of the patterns revealed by MRI, biopsy is recommended during the stage of osteitis to confirm the diagnosis. PMID- 7983109 TI - Vertebral growth after posterior spinal fusion for idiopathic scoliosis in skeletally immature adolescents. The effect of growth on spinal deformity. AB - We studied 29 girls and one boy with adolescent idiopathic scoliosis who were at Risser grade 0 at the time of posterior spinal fusion and were followed until maturity (mean 7.8 years). We used serial radiographs to measure the ratio of disc to vertebral height in the fused segments and to detect differential anterior spinal growth and assess its effect on scoliosis, vertebral rotation, kyphosis, and rib-vertebral-angle difference (RVAD). From one year after surgery to the latest review, the percentage anterior disc height decreased by nearly one half and the percentage posterior disc height by nearly one-third in the fused segments (p < 0.001). There was a 4 degree increase in mean Cobb angle (p < 0.001), 11 patients (37%) having an increase of between 6 degrees and 10 degrees. There was a significant increase in mean apical rotation by 2 degrees (p = 0.003), and four patients (13%) had an increase of between 6 degrees and 16 degrees. There was little change in kyphosis. There was an increase in mean RVAD by 4 degrees (p = 0.003), seven patients (23%) showing a reduction by 1 degree to 7 degrees, and 11 (37%) increases of between 6 degrees and 16 degrees. Spinal growth occurs after posterior fusion in adolescents who are skeletally immature, as a result of continued anterior vertebral growth. There is some progression of scoliosis, vertebral rotation, and RVAD, but little change in kyphosis. The increase in deformity is not enough to warrant the use of combined anterior and posterior fusion. The findings are relevant to the management of progressive curves, the timing and extent of surgery, and the prognosis for progression of deformity in this group of patients. PMID- 7983110 TI - Cervical spine injuries in the elderly. AB - We reviewed 41 patients over the age of 65 years (mean 76.5) who had suffered cervical spine injuries, 12 of them with neurological deficit. Eleven patients died during treatment, mostly from respiratory disease. Seven patients were treated by surgical stabilisation, five by halo traction, and the rest by rigid collars or halo-vests. The cervical injury was missed at the first examination in four patients. We conclude that most injuries can be treated by a rigid collar, and that the use of a halo-vest or surgical stabilisation are effective alternatives. Bed rest and traction are poorly tolerated by old people. There should be a high index of suspicion that any elderly patient who presents with a history of a fall or minor trauma may have a cervical spine injury. PMID- 7983111 TI - Sacral insufficiency fractures in the elderly. AB - Sacral insufficiency fractures are not uncommon in elderly patients. We have diagnosed 20 cases in a five-year period, and have reviewed the clinical records, radiographs, CT and bone scans. We also assessed the degree of osteoporosis by measuring bone density using dual-energy X-ray absorptiometry and bone histomorphometry, and monitored the patients' functional outcome. Bone scans were positive in all 20 patients, CT showed a fracture or sclerosis in 7 of 12 patients and was useful in excluding malignancy. Plain radiographs were the least helpful, showing sclerosis in only 4 of the 20 patients. Involutional osteoporosis with a reduced bone formation rate was the most common underlying cause. Seventeen patients had complete resolution of pain within nine months, and no patient lost independence in daily activities. Increased awareness of these fractures may help to avoid unnecessary investigation and treatment. Bedrest and analgesia followed by rehabilitation provide good relief of symptoms. PMID- 7983112 TI - Acute postpartum inflammatory sacroiliitis. A report of four cases. AB - We report four patients with unilateral postpartum sacroiliitis presenting with agonising unilateral pain, an elevated ESR, elevated alkaline phosphatase levels, leucocytosis and positive bone scans. The diagnosis of a non-infectious inflammatory cause was supported by the postpartum onset, the response to non steroidal anti-inflammatory drugs, negative aspiration cultures in two cases and the lack of changes in the sacroiliac joints on long-term follow-up radiographs. PMID- 7983113 TI - Internal fixation or hemiarthroplasty for undisplaced fractures of the femoral neck in octogenarians. AB - We compared the reoperation rate after internal fixation for minimally displaced or impacted intracapsular fractures of the femoral neck in patients aged 80 years and above with that in similar patients aged 65 to 79 years. We also compared the results of internal fixation with those of hemiarthroplasty for displaced intracapsular fracture in an age- and sex-matched group of elderly patients. We found that a significantly greater proportion of the older patients treated by internal fixation required reoperation than either the younger group or the age matched group treated by hemiarthroplasty. Our results indicate that internal fixation may not be the best treatment for extremely elderly patients with minimally displaced or impacted intracapsular fractures of the femoral neck. PMID- 7983114 TI - Low-dose irradiation and indomethacin prevent heterotopic ossification after acetabular fracture surgery. AB - From 1987 to 1991, we treated 53 patients with 54 fractures of the acetabulum by reconstruction through a posterior or an extended iliofemoral surgical approach. For prophylaxis against heterotopic ossification we used perioperative irradiation and indomethacin. Indomethacin was given as daily doses of 25 mg started within 24 hours of operation and continued for four weeks. Irradiation was by either 1200 cGy in three daily doses or by a single 700 cGy dose on the first postoperative day. All patients were followed for at least one year postoperatively and the severity of heterotopic ossification was recorded using the Brooker classification and correlated with hip mobility. The combination therapy proved very effective; 44 fractures showed no heterotopic ossification and ten showed Brooker class I. The functional results were good and there were no complications of this therapy. Irradiation with 1200 cGy did not appear to offer any therapeutic advantage over the 700 cGy dose. PMID- 7983115 TI - Algodystrophy after Colles fractures is associated with secondary tightness of casts. AB - We describe a direct method of measuring the tightness of plaster casts. Tightness was measured weekly in 23 consecutive patients with Colles' fractures. Six had objective signs of algodystrophy nine weeks after the fracture. In these patients the plaster cast was significantly tighter during the first three weeks than in patients who did not develop algodystrophy. The complex relationship between these findings is discussed. PMID- 7983116 TI - Improving the appearance of pin-site scars. AB - Broad, depressed pin-site scars often remain after the use of external fixators. We describe a new method of surgical revision which combines W-plasty to break up the outline of the scar, with burial of a dermal island to improve the surface contour. We obtained excellent results with this technique in five patients (19 scars). PMID- 7983117 TI - Cemented revision Charnley low-friction arthroplasty in patients with rheumatoid arthritis. AB - We assessed 41 patients with rheumatoid arthritis (47 hips) who had had revision hip arthroplasty, at an average follow-up of 7 years 4 months (2 to 19). The clinical results were excellent or satisfactory in 43 hips. Radiologically, 45 stems were secure. Fifteen sockets (36.6%) were radiologically loose. Three hips required rerevision. Socket failure is the predominant problem in rheumatoid patients after cemented revision arthroplasty. PMID- 7983118 TI - Does early micromotion of femoral stem prostheses matter? 4-7-year stereoradiographic follow-up of 84 cemented prostheses. AB - Roentgen stereophotogrammetry was used to measure the migration of the centre of the femoral head in 84 cemented Lubinus SP I hip arthroplasties (58 primary operations, 26 revisions). Four to seven years later, seven femoral components had been revised because of painful loosening. These implants showed greater subsidence, medial migration and posterior migration during the first two postoperative years than did the hips which had not been revised. Six months after operation, subsidence of more than 0.33 mm combined with a total migration of more than 0.85 mm predicted an increased risk of subsequent revision; the amount of subsidence at two years was an even better predictor. The probability of revision was greater than 50% if the subsidence at two years was 1.2 mm or more. PMID- 7983119 TI - Measurement of femoral vein blood flow during total hip replacement. Duplex ultrasound imaging with and without the use of a foot pump. AB - We examined ten femoral veins with duplex ultrasound during total hip replacement to demonstrate the operative manoeuvres which cause venous obstruction and to assess prophylactic measures which may overcome it. Exposure of the acetabulum by distraction of the femur with a hook was less likely to occlude flow than retraction with bone levers. Adequate exposure of the femoral shaft by adduction, flexion and either internal or external rotation caused cessation of flow in all cases. In four cases an A-V Impulse System foot pump was activated during periods of stasis. In each case it overcame the obstruction and produced peak velocities which were twice that of the resting state. In five cases, towards the end of the procedure, debris was seen travelling proximally through the femoral vein. PMID- 7983120 TI - Amyloid bone cysts of the femoral neck. Impending fractures treated by curettage and bone grafting. AB - We performed curettage and bone grafting of amyloid cysts of the femoral neck in five patients on long-term haemodialysis. All had had hip pain on weight-bearing. The duration of haemodialysis before the operation averaged 15 years and the average age of the patients was 53 years. All the large cystic lesions were located in the anterosuperior quadrant of the femoral neck. At operation, they were found to consist of fibrous tissue containing amyloid deposits. Postoperatively, all five patients had painless hips and the grafts had incorporated into the bone defects. PMID- 7983121 TI - Total knee arthroplasty after patellectomy. AB - We compared the outcome of total knee arthroplasty in 19 patients who had had previous patellectomy with the results in a matched series of arthroplasties performed on knees in which the patella was intact. The mean follow-up was 63 months (21 to 114). In the study group, the outcome was poor in five patients. There was instability in the coronal plane in three patients and persistent pain in four. Three supracondylar fractures occurred. The overall complication rate was 36%. In the control group, pain was relieved in every case and there were no complications. Total knee arthroplasty has a higher complication rate and inferior results if the knee has undergone prior patellectomy. PMID- 7983122 TI - Patellar resurfacing or retention in total knee arthroplasty. A prospective study of patients with bilateral replacements. AB - Patellofemoral problems are a common cause of morbidity and reoperation after total knee arthroplasty. We made a prospective study of 52 patients who had bilateral arthroplasty (104 knees) and in whom the patella was resurfaced on one side and not on the other. A movable-bearing prosthesis with an anatomical femoral groove was implanted on both sides by the same surgeon using an otherwise identical technique. The mean follow-up was 5.24 years (2 to 10). In the 30 available patients (60 knees) there was no difference between the two sides in subjective preference, performance on ascending and descending stairs or the incidence of anterior knee pain. Radiographs showed no differences in prosthetic alignment, femoral condylar height, patellar congruency or joint line position. The use of an appropriate prosthetic design and careful surgical technique can provide equivalent results after knee arthroplasty with or without patellar resurfacing. Given the indications and criteria, which we discuss, retention of the patellar surface is an acceptable option. PMID- 7983123 TI - Severe varus and valgus deformities treated by total knee arthroplasty. AB - We report a prospective case-controlled study which compared the outcome of knee replacement in seriously deformed and slightly deformed knees. There were 51 knees with varus or valgus deformity greater than 20 degrees matched for age, gender, disease, type of prosthesis and time of operation with a control group in which the alignment of the leg was within 5 degrees of normal. The clinical outcome at a mean 5.5 years was similar in the two groups. Some deformity persisted in 14 patients in the first group, 13 of whom were initially in valgus. These patients had a significantly poorer mean clinical outcome. Lateral dislocation or subluxation of the patella was found in four knees, all of which had had valgus deformity of 30 degrees or more. PMID- 7983124 TI - Anterior ankle arthrodesis with cross-screw fixation. A dowel graft method used in 20 cases. AB - We report a new method of ankle arthrodesis which combines an anterior approach with a dowel technique of bone grafting and screw fixation. In 20 ankles of 20 patients, ten with osteoarthritis, eight with rheumatoid arthritis and two others, we achieved 19 solid bony fusions and one painless fibrous ankylosis. The average time to union was 12.5 weeks. Patient satisfaction was high and the functional results were as good as for other reported methods, with fewer complications. PMID- 7983125 TI - Supramalleolar tibial osteotomy for haemophilic arthropathy of the ankle. AB - We report the results of supramalleolar varus osteotomy on seven ankles (in six patients) for haemophilic arthropathy and secondary valgus deformity. The operation reduced pain and the frequency of intra-articular bleeding while preserving joint function for a mean of nine years. The procedure is an attractive alternative to the more commonly used surgical option of arthrodesis. PMID- 7983126 TI - The origin of the long head of the biceps from the scapula and glenoid labrum. An anatomical study of 100 shoulders. AB - We dissected 105 cadaveric shoulders to study the origin of the tendon of the long head of biceps, and examined histologically the interrelationship between the tendon, the supraglenoid tubercle and the superior labrum of the glenoid. In all specimens approximately 50% of the biceps tendon arose directly from the superior glenoid labrum with the remainder attached to the supraglenoid tubercle. The main labral origin was from the posterior labrum in more than half of the specimens, and in a quarter this was the only labral attachment. On the basis of the biceps attachment to the anterior or posterior labrum, we distinguished four types of origin. These normal anatomical variations are significant for arthroscopic diagnosis and may help to explain the various patterns of injury seen in partial or complete detachment of the tendon, the labrum or both. PMID- 7983127 TI - Influence of type of medullary nail on the development of local infection. An experimental study of solid and slotted nails in rabbits. AB - Any operation involving the implantation of a foreign body increases the risk of infection. The implant material and its surface, the dead space, and any necrosis or vascular changes play a significant role in susceptibility to infection. We investigated the effect of the dead space in an intramedullary nail on the rate of local infection. We inoculated the intramedullary cavities of rabbit tibiae with various concentrations of a human pathogen, of Staphylococcus aureus strain, and then inserted either a solid or a hollow slotted stainless-steel nail. We found a significantly higher rate of infection after use of the slotted nail (59%) than after the solid nail (27%) (p < 0.05). PMID- 7983128 TI - The effect of intra-articular ACL reconstruction on the growth plates of rabbits. AB - We performed intra-articular reconstruction of the anterior cruciate ligament (ACL) with the semitendinosus tendon placed in 2 mm diameter tunnels in 21 skeletally immature rabbits. The operation caused 11% damage to the physis of the femur on the frontal plane and 3% of its cross-sectional area but no alteration of growth or axial deviation of the bone resulted. In the tibia, the operation caused 12% damage to the physis in the frontal plane and 4% of the cross sectional area. Two tibiae developed valgus deformities and one was shortened. Histological examination showed no areas of epiphysiodesis. There was no abnormality of growth-plate thickness in the two cases of tibia valga. Osseous metaplasia in the grafted tendons did not occur. The results suggest the need for careful evaluation of the percentage of damage to the growth plate before using intra-articular methods for reconstruction of the anterior cruciate ligament in adolescents. PMID- 7983129 TI - Excision of the trapezium for osteoarthritis at the base of the thumb. AB - We have assessed the results of 34 simple excisions of the trapezium, with no additional soft-tissue procedures, in 30 patients. At a median follow-up of five years (2 to 22), 16 thumbs (47%) were completely painfree and a further 10 (29%) were slightly painful after use. Nineteen thumbs (56%) had no functional disability, but thumb-pinch strength was reduced by about 20%. No patient had painful degeneration at the scaphotrapezial pseudarthrosis. PMID- 7983130 TI - Ultrasonic features of acute osteomyelitis in children. AB - The ultrasonic findings in 38 children with osteomyelitis of the limb bones were analysed in four time-related groups based on the interval between the onset of symptoms and the ultrasonic examination. Deep soft-tissue swelling was the earliest sign of acute osteomyelitis; in the next stage there was periosteal elevation and a thin layer of subperiosteal fluid, and in some cases this progressed to form a subperiosteal abscess. The later stages were characterised by cortical erosion, which was commonly present in those who had had symptoms for more than a week. Concurrent septic arthritis was revealed in 11 patients, most frequently in association with osteomyelitis of the proximal femur or the distal humerus. Four weeks after clinical cure, ultrasonic examination showed no abnormalities. Ultrasonography is therefore a useful additional method for the diagnosis and assessment of osteomyelitis and its complications. PMID- 7983132 TI - Imaging the acetabulum in children with cerebral palsy. PMID- 7983133 TI - Curly and overlapping toes in congenital pseudarthrosis of the tibia. PMID- 7983131 TI - Bone-marrow transplantation in Hurler's syndrome. Effect on skeletal development. AB - Between 1980 and 1988, displacement bone-marrow transplantation was performed on 25 children with Hurler's syndrome (type-1 mucopolysaccharidosis). We describe the musculoskeletal development of 11 of the 12 surviving children and the orthopaedic procedures undertaken to treat progressive thoracolumbar kyphosis, hip subluxation and carpal tunnel syndrome. We found abnormal bone modelling, focal failures of ossification and an avascular disorder of the femoral head in every patient and offer an explanation for these phenomena. Increasing valgus deformity of the knees and progressive generalised myopathy caused loss of mobility as the children entered adolescence. The benefit of bone-marrow transplantation as a treatment for the skeletal disorders of Hurler's syndrome is limited by the poor penetration of the musculoskeletal tissues by the enzyme derived from the leucocytes. PMID- 7983134 TI - Pyoderma gangrenosum affecting the hand. PMID- 7983135 TI - Median nerve palsy after posterolateral elbow dislocation. PMID- 7983136 TI - A new operation for reconstruction of the femoral neck. PMID- 7983137 TI - Wedging casts. PMID- 7983138 TI - Imaging in spinal tuberculosis. PMID- 7983139 TI - Proprioception in the knee. PMID- 7983140 TI - Bone-marrow oedema, transient osteoporosis, and algodystrophy. PMID- 7983141 TI - Aetiology of club foot. PMID- 7983142 TI - A calcineurin-like gene ppb1+ in fission yeast: mutant defects in cytokinesis, cell polarity, mating and spindle pole body positioning. AB - A calcineurin (type 2B)-like protein phosphatase gene designated ppb1+ was isolated from the fission yeast Schizosaccharomyces pombe. The predicted amino acid sequence was 57% identical to rat PP2B alpha. ppb1 null mutant could form colonies at 33 degrees C but the size of the colonies was small at 22 degrees C. Cytokinesis was greatly delayed at 22 degrees C, and a large number of multi septate cells were produced. The cell polarity control was impaired, causing branched cells. ppb1 null was virtually sterile. These phenotypes were rescued by a plasmid carrying the ppb1+ gene. Multi-septate cells were also produced in wild type at 22 degrees C by cyclosporin A, an inhibitor of calcineurin. This drug effect was enhanced in stst1 null mutant, which was hypersensitive to various drugs and cations. ppb1 null was not affected by cyclosporin A, consistent with the hypothesis that ppb1 is its target. Double-mutant analysis indicated that ppb1 had a function related to that of two other phosphatases, type 1-like dis2 and 2A-like ppa2.ppb1 null-sts1 null showed the severe multi-septate phenotype in the absence of cyclosporin A. ppb1+ and sts1+ gene functions are related. The double mutant ppb1-sts5 was lethal, indicating that the ppb1+ gene shared an essential function with the sts5+ gene. Overexpression of ppb1+ caused anomalies in cell and nuclear shape, microtubule arrays and spindle pole body positioning in interphase cells. Thus the ppb1+ gene appears to be involved in cytokinesis, mating, transport, nuclear and spindle pole body positioning, and cell shape. PMID- 7983143 TI - Regulation of myosin regulatory light chain phosphorylation via cyclic GMP during chemotaxis of Dictyostelium. AB - Previous studies on the chemotactic movement of Dictyostelium have indicated a role for cyclic GMP in regulating the association of myosin II with the cytoskeleton. In this study we have examined the part played by phosphorylation of the 18 kDa myosin regulatory light chain in this event. Using streamer F mutant NP368 (which is deficient in the structural gene for cyclic GMP-specific phosphodiesterase) we find that, for the regulatory light chain kinase, the major peak of phosphorylation is delayed compared to the parental control strain XP55, occurring at 80 seconds rather than about 30 seconds in XP55. In two independently derived mutants that are unable to increase their cellular concentration of cyclic GMP (above basal levels) in response to a chemotactic stimulus of cyclic AMP (KI-10 and SA219), no increase in the phosphorylation of the light chain occurred, or movement of myosin II to the cytoskeleton. We also find a smaller peak of light chain phosphorylation that occurs within 10 seconds of cyclic AMP stimulation of the amoebae, and which is absent in the cyclic GMP unresponsive strains. We conclude that cyclic GMP is involved in regulating light chain phosphorylation in this system. The possible significance of these findings is discussed and a model that relates these findings to published data on cytoskeletal myosin changes during chemotaxis is presented. PMID- 7983144 TI - Sites in human nuclei where DNA damaged by ultraviolet light is repaired: visualization and localization relative to the nucleoskeleton. AB - The repair of damage induced in DNA by ultraviolet light involves excision of the damage and then repair synthesis to fill the gap. We investigated the sites of repair synthesis using MRC-5 fibroblasts and HeLa cells in G1 phase. Cells were encapsulated in agarose microbeads to protect them during manipulation, irradiated, incubated to allow repair to initiate, and permeabilized with streptolysin O to allow entry of labelled triphosphates; [32P]dTTP was incorporated into acid-insoluble material in a dose-dependent manner. Incubation with biotin-16-dUTP allowed sites of incorporation to be indirectly immunolabeled using a FITC-conjugated antibody; sites were not diffusely spread throughout nuclei but concentrated in discrete foci. This is similar to sites of S phase activity that are attached to an underlying nucleoskeleton. After treatment with an endonuclease, most repaired DNA electroeluted from beads with chromatin fragments; this was unlike nascent DNA made during S phase and suggests that repaired DNA is not as closely associated with the skeleton. However, the procedure destroyed repair activity, so repaired DNA might be attached in vivo through a polymerase that was removed electrophoretically. Therefore this approach cannot be used to determine decisively whether repair sites are associated with a skeleton in vivo. PMID- 7983145 TI - Sites in human nuclei where damage induced by ultraviolet light is repaired: localization relative to transcription sites and concentrations of proliferating cell nuclear antigen and the tumour suppressor protein, p53. AB - The repair of damage induced in DNA by ultraviolet light involves excision of the damaged sequence and synthesis of new DNA to repair the gap. Sites of such repair synthesis were visualized by incubating permeabilized HeLa or MRC-5 cells with the DNA precursor, biotin-dUTP, in a physiological buffer; then incorporated biotin was immunolabeled with fluorescent antibodies. Repair did not take place at sites that reflected the DNA distribution; rather, sites were focally concentrated in a complex pattern. This pattern changed with time; initially intense repair took place at transcriptionally active sites but when transcription became inhibited it continued at sites with little transcription. Repair synthesis in vitro also occurred in the absence of transcription. Repair sites generally contained a high concentration of proliferating cell nuclear antigen but not the tumour-suppressor protein, p53. PMID- 7983146 TI - Transfection of rat dermal papilla cells with a gene encoding a temperature sensitive polyomavirus large T antigen generates cell lines retaining a differentiated phenotype. AB - The dermal papilla is a discrete group of cells at the base of the hair follicle and is implicated in controlling the hair growth cycle. Early passage dermal papilla cells can induce hair growth in vivo, but, upon further culturing, this property is lost. In order to study the events occurring in hair induction, a representative dermal papilla cell line was required. We have transfected passage 1 rat vibrissa dermal papilla cells with a polyomavirus large T gene encoding a temperature-sensitive T antigen, and generated permanent cell lines in which the immortalizing function can be switched off by temperature shift. The cells established without crisis, resembled cells in the starting population, and retained the aggregative properties of early passage dermal papilla cells. Growth studies were performed on the immortalized cell lines, which showed that transferring the cells to the restrictive temperature for the large T gene product resulted in cell senescence or quiescence, and changes in morphology. Implantation of cell pellets into the ears of immunologically compatible rats showed that the immortal cells retained hair-inductive ability. Cytokines are believed to have an important role in the control of hair growth. The pattern of cytokine gene expression in the immortal cell lines was compared with early passage dermal papilla cells and a non-hair-inducing dermal papilla cell line, using reverse transcriptase-polymerase chain reaction. Epidermal growth factor, tumour necrosis factor, and interleukin-1a were detected in the immortalized and non-hair-inducing dermal papilla cell lines, but were absent in passage 2 dermal papilla cells. All other cytokines examined were detected in all the cell types under study. These results demonstrate that the polyomavirus large Ttsa immortalized dermal papilla cell lines are very similar to passage 2 dermal papilla cells and thus provide a good model for hair growth studies. Cytokine expression profiles indicate that the expression of several cytokines may be implicated in hair induction. Further studies are under way to investigate the relationship between cytokine expression and the hair growth cycle. PMID- 7983147 TI - Modulation of alpha-actinin levels affects cell motility and confers tumorigenicity on 3T3 cells. AB - alpha-Actinin is an abundant actin crosslinking protein, also localized at adherens type junctions. In adhesion plaques, alpha-actinin can link the actin filaments to integrin via vinculin and talin, or directly by binding to the cytoplasmic domain of beta 1-integrin. The expression of alpha-actinin is rapidly elevated in growth-activated quiescent cells, and is reduced in SV40-transformed 3T3 cells and various differentiating cell types (reviewed by Gluck, U., Kwiatkowski, D. J. and Ben-Ze'ev, A. Proc. Nat. Acad. Sci. USA 90, 383-387, 1993). To study the effect of changes in alpha-actinin levels on cell behavior, alpha-actinin expression was elevated in 3T3 cells by transfection with a full length human nonmuscle alpha-actinin cDNA. To suppress alpha-actinin levels, 3T3 cells were transfected with an antisense alpha-actinin cDNA construct. Cells overexpressing alpha-actinin by 40-60% displayed a significant reduction in cell motility, as demonstrated by their slower locomotion into an artificial wound, and by forming shorter phagokinetic tracks on colloidal gold-coated substrata. 3T3 cells in which the expression of alpha-actinin was reduced to 25-60% of control levels, after antisense alpha-actinin transfection, had an increased cell motility. Moreover, such alpha-actinin-deficient 3T3 cells formed tumors upon injection into nude mice. The results demonstrate that modulations in alpha actinin expression can affect, in a major way, the motile and tumorigenic properties of cells, and support the view that decreased alpha-actinin expression could be a common regulatory pathway to malignant transformation of 3T3 cells. PMID- 7983148 TI - The mode of anchorage to the cell surface determines both the function and the membrane location of Thy-1 glycoprotein. AB - The surface glycoprotein, Thy-1, when expressed by transfection in NG115/401L neural cells, inhibits their neurite outgrowth over astrocytes. We have investigated the role of the glycosylphosphatidylinositol anchor of Thy-1 in this inhibition. Hybrid molecules, in which the lipid anchor was replaced by polypeptide transmembrane domains, were expressed by transfection. Lines expressing Thy-1 with the transmembrane and full cytoplasmic domains of NCAM-140, or with the transmembrane and truncated cytoplasmic domain of CD8, were not inhibited in their ability to extend neurites over astrocytes. Truncation of the cytoplasmic domain of NCAM-140 to just two amino acids, however, produced a transmembrane form of Thy-1 that, when expressed at high levels, inhibited neurite outgrowth. All forms of Thy-1 were concentrated in clusters that occurred primarily on fine filopodia. In double transfectants expressing normal Thy-1 and Thy-1 with the full NCAM cytoplasmic tail, the clusters of each form were separate, with no instances of the transmembrane form being found within the clusters of lipid-anchored Thy-1. Thy-1 with the two-amino-acid cytoplasmic domain of NCAM also occurred in clusters separate from those occupied by lipid anchored Thy-1, but substantial 'invasion' of the clusters of normal Thy-1 by this transmembrane construct occurred. We suggest that the ability of this hybrid protein to enter the lipid-anchored clusters enables it to activate the signalling pathways that normal Thy-1 uses. Thus the membrane anchor, in targetting Thy-1 to different microdomains on the cell surface, determines its ability to inhibit neurite outgrowth on astrocytes. PMID- 7983149 TI - Nuclear transport of the U2 snRNP-specific U2B'' protein is mediated by both direct and indirect signalling mechanisms. AB - Experiments investigating the nuclear import of the U2 snRNP-specific B'' protein (U2B'') are presented. U2B'' nuclear transport is shown to be able to occur independently of binding to U2 snRNA. The central segment of the protein (amino acids 90-146) encodes an unusual nuclear localization signal (NLS) that is related to that of the U1 snRNP-specific A protein. However, nuclear import of U2B'' does not depend on this NLS. Sequences in the N-terminal RNP motif of the protein are sufficient to direct nuclear transport, and evidence is presented that the interaction of U2B'' with the U2A' protein mediates this effect. This suggests that U2B'' can 'piggy-back' to the nucleus in association with U2A', and thus be imported to the nucleus by two different mechanisms. U2A' nuclear transport, on the other hand, can occur independently of both U2B'' binding and of U2 snRNA. PMID- 7983151 TI - A homologue of the human regulator of mitotic spindle assembly protein (RMSA-1) is present in crane fly and is associated with meiotic chromosomes. AB - In a previous study, we have shown that a newly identified chromosomal protein, RMSA-1 (Regulator of Mitotic Spindle Assembly-1), identified and cloned using a human autoimmune, serum, is essential for mitotic spindle assembly; we proposed that RMSA-1 was a previously unknown physiological substrate for cdc 2 kinase. In the present study, we show that this protein is present in crane fly and is associated with the chromosomes of spermatocytes. A 31 kDa molecule in extracts from crane-fly nuclei, isolated from larvae, pupae and adults, reacts with affinity-purified anti-RMSA-1 autoantibody, shown by immunoblotting. The autoantibody reacts, as shown by immunofluorescence, with crane-fly spermatocyte chromosomes in prophase through anaphase of both meiosis-1 and meiosis-II but does not react with preprophase or telophase nuclei or with spermatid nuclei. In all meiotic stages, the crane-fly sex chromosomes stain more intensely than the autosomes. We conclude that, since RMSA-1 is present in insect and mammalian cells, it is conserved across a variety of animal species. Further, since RMSA-1 binds to chromosomes in meiotic cells, it also may be essential for assembly of the meiotic spindle. PMID- 7983150 TI - Evidence that the 16 kDa proteolipid (subunit c) of the vacuolar H(+)-ATPase and ductin from gap junctions are the same polypeptide in Drosophila and Manduca: molecular cloning of the Vha16k gene from Drosophila. AB - The 16 kDa proteolipid (subunit c) of the eukaryotic vacuolar H(+)-ATPase (V ATPase) is closely related to the ductin polypeptide that forms the connexon channel of gap junctions in the crustacean Nephrops norvegicus. Here we show that the major protein component of Manduca sexta gap junction preparations is a 16 kDa polypeptide whose N-terminal sequence is homologous to ductin and is identical to the deduced sequence of a previously cloned cDNA from Manduca (Dow et al., Gene, 122, 355-360, 1992). We also show that a Drosophila melanogaster cDNA, highly homologous to the Manduca cDNA, can rescue Saccharomyces cerevisiae, defective in V-ATPase function, in which the corresponding yeast gene, VMA3, has been inactivated. Evidence is presented for a single genetic locus (Vha16) in Drosophila, which in adults at least contains a single transcriptional unit. Taken together, the data suggest that in Drosophila and Manduca, the same polypeptide is both the proteolipid subunit c component of the V-ATPase and the ductin component of gap junctions. The intron/exon structure of the Drosophila Vha16 is identical to that of a human Vha16 gene, and is consistent with an ancient duplication of an 8 kDa domain. A pilot study for gene inactivation shows that transposable P-elements can be easily inserted into the Drosophila ductin Vha16 gene. Although without phenotypic consequences, these can serve as a starting point for generation of null alleles. PMID- 7983152 TI - Cleavage furrow: timing of emergence of contractile ring actin filaments and establishment of the contractile ring by filament bundling in sea urchin eggs. AB - Cleavage furrow formation at the first cell division of sea urchin and sand dollar eggs was investigated in detail by fluorescence staining of actin filaments with rhodamine-phalloidin of either whole eggs or isolated egg cortices. Cortical actin filaments were clustered at anaphase and then the clusters became fibrillar at the end of anaphase. The timing when the contractile ring actin filaments appear was precisely determined in the course of mitosis: accumulation of the contractile ring actin filaments at the equatorial cell cortex is first noticed at the beginning of telophase (shortly before furrow formation), when the chromosomal vesicles are fusing with each other. The accumulated actin filaments were not well organized at the early stage but were organized into parallel bundles as the furrowing progressed. The bundles were finally fused into a tightly packed filament belt. Wheat germ agglutinin (WGA) binding sites were distributed on the surface of the egg in a manner similar to the actin filaments after anaphase. The WGA-binding sites became accumulated in the contractile ring together with the contractile ring actin filaments, indicating an intimate relationship between these sites and actin filament anchoring sites on the plasma membrane. Myosin also appeared in the contractile ring together with the actin filaments. The 'cleavage stimulus', a signal hypothesized by Rappaport (reviewed by R. Rappaport (1986) Int. Rev. Cytol. 105, 245-281) was suggested to induce aggregation or bundling of the actin filaments in the cortical layer. PMID- 7983153 TI - The nullo protein is a component of the actin-myosin network that mediates cellularization in Drosophila melanogaster embryos. AB - After the 13th nuclear division cycle of Drosophila embryogenesis, cortical microfilaments are reorganized into a hexagonal network that drives the subsequent cellularization of the syncytial embryo. Zygotic transcription of the nullo and serendipity-alpha genes is required for normal structuring of the microfilament network. When either gene is deleted, the network assumes an irregular configuration leading to the formation of multinucleate cells. To investigate the role of these genes during cellularization, we have made monoclonal antibodies to both proteins. The nullo protein is present from cycle 13 through the end of cellularization. During cycle 13, it localizes between interphase actin caps and within metaphase furrows. In cellularizing embryos, nullo co-localizes with the actin-myosin network and invaginates along with the leading edge of the plasma membrane. The serendipity-alpha (sry-alpha) protein co localizes with nullo protein to the hexagonal network but, unlike the nullo protein, it localizes to the sides rather than the vertices of each hexagon. Mutant embryos demonstrate that neither protein translationally regulates the other, but the localization of the sry-alpha protein to the hexagonal network is dependent upon nullo. PMID- 7983154 TI - Molecular phylogeny of the kinesin family of microtubule motor proteins. AB - The rapidly expanding kinesin family of microtubule motor proteins includes proteins that are involved in diverse microtubule-based functions in the cell. Phylogenetic analysis of the motor regions of the kinesin proteins reveals at least five clearly defined groups that are likely to identify kinesins with different roles in basic cellular processes. Two of the groups are consistent with overall sequence similarity, while two groups contain proteins that are related in overall structure or function but show no significant sequence similarity outside the motor domain. One of these groups consists only of kinesin proteins with predicted C-terminal motor domains; another includes only kinesins required for mitotic spindle bipolarity. Drosophila Nod, presently an ungrouped protein, may represent a class of kinesins that, like the myosin I proteins, function as monomers. The analysis indicates that many types of kinesin proteins exist in eukaryotic organisms. At least two of the five groups identified in this analysis are expected to be present in most, or all, eukaryotes. PMID- 7983155 TI - Movement of membrane tubules along microtubules in vitro: evidence for specialised sites of motor attachment. AB - We have studied the microtubule-dependent formation of tubular membrane networks in vitro, using a heterologous system composed of Xenopus egg cytosol combined with rat liver membrane fractions enriched in either Golgi stacks or rough endoplasmic reticulum. The first step in membrane network construction involves the extension of membrane tubules along microtubules by the action of microtubule based motor proteins. We have observed for both membrane fractions that 80-95% of moving tubule tips possess a distinct globular domain. These structures do not form simply as a consequence of motor protein activity, but are stable domains that appear to be enriched in active microtubule motors. Negative stain electron microscopy reveals that the motile globular domains associated with the RER networks are generally smaller than those observed in networks derived from a crude Golgi stack fraction. The globular domains from the Golgi fraction are often packed with very low density lipoprotein particles (the major secretory product of hepatocytes) and albumin, which suggests that motor proteins may be specifically enriched in organelle regions where proteins for export are accumulated. These data raise the possibility that the concentration of active motor proteins into specialised membrane domains may be an important feature of the secretory pathway. PMID- 7983156 TI - Microtubule tracks can be detected in mouse oocytes with an antibody directed against a calcium transporter. AB - In metaphase II-arrested mouse oocytes, most microtubules are found in the meiotic spindle, a structure that remains stable for hours despite microtubule instability. Microtubule organizing centres (MTOCs) are present at the poles of the spindle and in the cytoplasm, but the latter nucleate very few microtubules. This particular organization of the microtubule network enabled us to observe the unexpected behaviour of a protein that can associate with microtubules. We compared the distribution of a mitosis-activated calcium transport system with that of the microtubule network, by immunofluorescence, using two monoclonal antibodies, one directed against a component of the calcium transport system (7/13), and the other against the common tyrosinated form of alpha-tubulin (YL1/2). The 7/13 staining was associated with the spindle microtubules and with the kinetochore area. In addition, we observed many asters in the cytoplasm, around the cytoplasmic MTOCs. The majority of these asters were not stained with the antitubulin antibody. Moreover, these 7/13 asters either disappeared after nocodazole treatment or were enlarged after taxol treatment. Using a confocal microscope, we observed single fibres that were stained with both antibodies: the extremity furthest from the MTOC (corresponding to the + end of the microtubule) being detected by the 7/13 antibody only. All these observations suggest that the 7/13 antigen is associated with microtubule tracks that persist a few minutes after microtubule depolymerization. The possible role of these tracks in microtubule regrowth is discussed. PMID- 7983157 TI - Molecular characterization of two functional domains of CLIP-170 in vivo. AB - CLIP-170 is a microtubule-binding protein isolated from HeLa cells that is involved in the interaction of endosomes with microtubules. The basic N-terminal domain of CLIP-170 binds to microtubules in vitro. To characterize further the functional domains of this cytoplasmic linker protein, we have transiently expressed intact and mutant forms of CLIP-170 in mammalian cells (HeLa and Vero cells) and show that the tandem repeat present in the N-terminal domain is essential for its binding to microtubules in vivo as previously found in vitro. With increasing levels of expression of CLIP-170, the sites with which the peripheral ends of microtubules interact enlarge, eventually forming large patches, which finally lead to the apparent bundling of microtubules. These patches do not form when the C-terminal domain is absent from the transfected protein. Modification of the microtubule-binding region, particularly of the tandem repeat motif, modulates the binding of CLIP-170 to microtubules. Overexpressed CLIP-170 appears neither to interact with nor to influence the organization of the intermediate filaments, and collapsing the network of intermediate filaments with microinjected antibodies against vimentin has no effect on the distribution of CLIP-170. These data suggest that CLIP-170 has at least two functional domains in vivo, an N-terminal microtubule-binding domain, and a C-terminal domain that is involved in the anchoring of microtubules to peripheral cytoplasmic structures. PMID- 7983159 TI - Actin microfilaments are associated with the migrating nucleus and the cell cortex in the green alga Micrasterias. Studies on living cells. AB - Rhodamine-phalloidin or FITC-phalloidin has been injected in small amounts into living, developing cells of Micrasterias denticulata and the stained microfilaments visualized by confocal laser scanning microscopy. The results reveal that two different actin filament systems are present in a growing cell: a cortical actin network that covers the inner surface of the cell and is extended far into the tips of the lobes in both the growing and the nongrowing semicell; it is also associated with the surface of the chloroplast. The second actin system ensheathes the nucleus at the isthmus-facing side during nuclear migration. Its arrangement corresponds to that of the microtubule system that has been described in earlier electron microscopic investigations. The spatial correspondence between the distribution of actin filaments and microtubules suggests a cooperation between both cytoskeleton elements in generating the motive force for nuclear migration. The function of the cortical actin network is not yet clear. It may be involved in processes like transport and fusion of secretory vesicles and may also function in shaping and anchoring the chloroplast. PMID- 7983158 TI - Structural diversity of band 4.1 superfamily members. AB - Several proteins contain the domain homologous to the N-terminal half of band 4.1 protein, indicating the existence of a superfamily. The members of this 'band 4.1' superfamily are thought to play crucial roles in the regulation of cytoskeleton-plasma membrane interaction just beneath plasma membranes. We examined the structural diversity of this superfamily by means of the polymerase chain reaction using synthesized mixed primers. We thus identified many members of the band 4.1 superfamily that were expressed in mouse teratocarcinoma F9 cells and mouse brain tissue. In total, 15 cDNA clones were obtained; 8 were identical to the corresponding parts of cDNAs for the known members, while 7 appeared to encode novel proteins (NBL1-7: novel band 4.1-like proteins). Sequence analyses of these clones revealed that the band 4.1 superfamily can be subdivided into 5 gene families; band 4.1 protein, ERM (ezrin/radixin/moesin/merlin/NBL6/NBL7+ ++), talin, PTPH1 (PTPH1/PTPMEG/NBL1-3), and NBL4 (NBL4/NBL5) families. The NBL4 family was first identified here, and the full-length cDNA encoding NBL4 was cloned. The deduced amino acid sequence revealed a myristoylation site, as well as phosphorylation sites for A-kinase and tyrosine kinases in its N-terminal half, suggesting its involvement in the phosphorylation-dependent regulation of cellular events just beneath the plasma membrane. In this study, we describe the initial characterization of these new members and discuss the evolution of the band 4.1 superfamily. PMID- 7983160 TI - Identification of two N-terminal non-alpha-helical domain motifs important in the assembly of glial fibrillary acidic protein. AB - The non-alpha-helical N-terminal domain of intermediate filament proteins plays a key role in filament assembly. Previous studies have identified a nonapeptide motif, SSYRRIFGG, in the non-alpha-helical N-terminal domain of vimentin that is required for assembly. This motif is also found in desmin, peripherin and the type IV intermediate filament proteins. GFAP is the only type III intermediate filament protein in which this motif is not readily identified. This study has identified two motifs in the non-alpha-helical N-terminal domain of mouse GFAP that play important roles in GFAP assembly. One motif is located at the very N terminus and has the consensus sequence, MERRRITS-ARRSY. It has some characteristics in common with the vimentin nonapeptide motif, SSYRRIFGG, including its location in the non-alpha-helical N-terminal domain and a concentration of arginine residues. Unlike the vimentin motif in which even conserved sequence changes affect filament assembly, the GFAP consensus sequence, MERRRITS-ARRSY, can be replaced by a completely unrelated sequence; namely, the heptapeptide, MVRANKR, derived from the lambda cII protein. When fused to GFAP sequences with sequential deletions of the N-terminal domain, the lambda cII heptapeptide was used to help identify a second motif, termed the RP-box, which is located just upstream of the GFAP alpha-helical rod domain. This RP-box affected the efficiency of filament assembly as well as protein-protein interactions in the filament, as shown by sedimentation assays and electron microscopy. These results are supported by previous data, which showed that the dramatic reorganization of GFAP within cells was due to phosphorylation dephosphorylation of a site located in this RP-box. The results in this study suggest the RP-box motif to be a key modulator in the mechanism of GFAP assembly, and support a role for this motif in both the nucleation and elongation phases of filament assembly. The RP-box motif in GFAP has the consensus sequence, RLSL-RM PP. Sequences similar to the GFAP RP-box motif are also to be found in vimentin, desmin and peripherin. Like GFAP, these include phosphorylation and proteolysis sites and are adjacent to the start of the central alpha-helical rod domain, suggesting that this motif of general importance to type III intermediate filament protein assembly. PMID- 7983161 TI - Dephosphorylation of the largest neurofilament subunit protein influences the structure of crossbridges in reassembled neurofilaments. AB - Phosphorylation-dependent change in electrophoretic mobility is the most unique characteristic of NF-H, the largest molecular mass subunit of the neurofilament. We dephosphorylated NF-H using Escherichia coli alkaline phosphatase, then reassembled it into neurofilaments with NF-M and NF-L, and into NF-H filaments with NF-H alone. We compared these dephosphorylated filaments with control: projections by low-angle rotary-shadow, crossbridges by quick-freeze deep-etch, and core filament packing density by thin-section electron microscopy. Projections in the dephosphorylated filaments were basically similar in structure to those in control, although there was a tendency for them to be wider and less dense, especially in NF-H filaments. Dephosphorylated filaments were still able to form crossbridges between core filaments, but their crossbridges were significantly wider, less dense, more branched and more irregular than crossbridges in control, and core filaments were more densely packed. These structural differences may be brought about by the removal of phosphate groups from NF-H tail and consequent reduction of electrostatic repulsion between adjacent crossbridges extending from the same core filament. The results indicate that phosphorylation of NF-H is necessary for forming well developed crossbridges, straight and at constant intervals, like those of in vivo axonal neurofilaments. PMID- 7983162 TI - Immunocytochemical detection of extracellular annexin II in cultured human skin keratinocytes and isolation of annexin II isoforms enriched in the extracellular pool. AB - Monoclonal antibodies were raised against trypsinized human skin epidermal cells and selected for their staining of the epidermal cells in a cell periphery pattern. One antibody, CP-1, immunoprecipitated a 36 kDa protein that was identified as annexin II heavy chain by microsequencing of a CNBr-generated peptide fragment from the antigen and by cross-identification with another anti annexin II antibody. In addition to staining a broad cell periphery band in keratinocytes, CP-1 also detected annexin II outside and in between the top layer cells before cell permeabilization. Double-labeling of annexin II and F-actin revealed a distinct topographical relationship between the two, with intercellular annexin II flanked by the submembranously located actin of the juxta-positioned cells. Annexin II was isolated from cultured keratinocytes via immunoaffinity column chromatography in one step, using the same monoclonal antibody CP-1 and was found to be resolved into multiple isoforms when analyzed by two-dimensional gel electrophoresis. The predominant components of annexin II were basic, with pI of 6.5-8.5, and some of them formed disulfide-linked monomeric multimers under non-reducing conditions. Acidic annexin II isoforms with pI 5.4-5.8 were barely detectable among the total annexin II isolated but were selectively enriched in an extracellular pool created by 0.05% ethylenediaminetetraacetic acid (EDTA) dispersion of the cultured cells into single cell suspensions. Furthermore, they can be separated from the rest of annexin II by using a different elution condition. A 46 kDa protein, the identity of which is unclear, co-eluted with the acidic isoforms in the EDTA washes. These acidic isoforms, which co-eluted with the 46 kDa protein, are suspected of corresponding to the extracellular annexin II detected immunocytochemically. PMID- 7983163 TI - Ultrastructural visualization of cross-linked protein features in epidermal appendages. AB - Upon vigorous extraction with ionic detergent under reducing conditions, the macroscopic structures of mammalian hair, bird feather and horny teeth of the hagfish become swollen and flexible but were substantially preserved. In each case, removal in this way of solubilizable constituents, such as disulfide-bonded keratins and associated matrix proteins, left a residue of epsilon-(gamma glutamyl)lysine cross-linked protein. Residual features in hair included cell envelopes in the cortex, cell envelopes and intracellular deposits in the medulla, and nearly the entire cuticle cells. In feather, extraction left largely intact the macroscopic barb structures but caused collapse of the rachis. In both rachis and barbs, considerable material resembling cell envelopes remained. In extracted hagfish teeth the cellular organization was clearly visible microscopically, including cell borders and remnant nuclei. Unlike the cornified envelopes of mature epidermal keratinocytes, which appear as doublets, reflecting their formation immediately beneath each plasma membrane of apposing cells, the borders of cells of hair cortex and hagfish teeth appeared single and continuous from one cell to the next. Thus the observed cross-linked features comprised four types: (i) condensation immediately beneath the plasma membrane (feather, hair medulla and cuticle) similar to cornified envelopes of epidermal keratinocytes; (ii) deposition between cells (hair cortex, horny teeth); (iii) cytoplasmic deposits (hair cuticle and medulla); and (iv) nuclear condensation (hair medulla, horny teeth). The results emphasize the importance of transglutaminases and their substrate proteins for the function of epidermal appendages and may provide a useful diagnostic test for perturbation of their normal structures. PMID- 7983164 TI - Expression and localization of the phosphoglucomutase-related cytoskeletal protein, aciculin, in skeletal muscle. AB - Recently, a 60/63 kDa cytoskeletal protein, highly homologous to the glycolytic enzyme phosphoglucomutase (PGM 1), was isolated from smooth muscle tissue and shown to localize in various adherens-type junctions of muscle and some nonmuscle cells. Since this protein, tentatively named 'aciculin', was enriched in muscle tissues and cells, we have attempted to study its expression and localization during myodifferentiation. C2C12 mouse myoblasts did not express any aciculin before cell fusion in culture. Immediately after cell fusion aciculin became detectable and its content continued to rise during myotube maturation. In early myotubes aciculin appeared first at cell tips and was predominantly localized to focal adhesions of immature myotubes. As myotubes matured in culture, aciculin became associated with growing myofibrils, and finally was found redistributed in striations, corresponding to sarcomere Z-discs. Immunoblotting showed that aciculin content in chicken breast skeletal muscle remained very low until day 11 of embryogenesis, but significantly increased in late prenatal and early postnatal development. By immunofluorescence, aciculin was not revealed in thigh skeletal muscle of day 11 chicken embryos, but was prominently localized at myotendinous junctions in thigh muscle of day 16 embryos. Myotendinous junctions appeared to be major sites of aciculin accumulation in developing and mature skeletal muscle fibers in vivo, suggesting some role for this protein in thin filament-membrane interactions and, potentially, in force transmission at these cell-matrix contacts. In adult skeletal muscle faint aciculin staining appeared at the sarcolemma and as striations in register with Z-discs. Since the protein was not identified in glycerinated myofibrils but was localized to striations in C2C12 myotubes and within the limited areas on skeletal muscle tissue sections, we conclude that aciculin is a component of skeletal muscle costameres. In cultured C2C12 myotubes we found some codistribution of aciculin with clusters of acetylcholine receptors, suggesting its presence at neuromuscular junctions. However, we did not detect any significant concentration of aciculin at neuromuscular junctions in both embryonic and adult skeletal muscle. Taken together, our data show that aciculin expression in skeletal muscle is differentiation-dependent and upregulated during muscle development, and that this novel cytoskeletal protein is a component of various cell-matrix adherens junctions in muscle cells. PMID- 7983165 TI - An LI and ML motif in the cytoplasmic tail of the MHC-associated invariant chain mediate rapid internalization. AB - Invariant chain (Ii) is a transmembrane protein that associates with the MHC class II molecules in the endoplasmic reticulum. Two regions of the 30 residue cytoplasmic tail of Ii contain sorting information able to direct Ii to the endocytic pathway. The full-length cytoplasmic tail of Ii and the two tail regions were fused to neuraminidase (NA) forming chimeric proteins (INA). Ii is known to form trimers and when INA was transfected into COS cells it assembled as a tetramer like NA. The INA molecules were targeted to the endosomal pathway and cotransfection with Ii showed that both molecules appeared in the same vesicles. By labelling the INA fusion proteins with iodinated antibody it was found that molecules with either endocytosis signal were expressed at the plasma membrane and internalized rapidly. Point mutations revealed that an LI motif within the first region of the cytoplasmic tail and an ML motif in the second region were essential for efficient internalization. The region containing the LI motif is required for Ii to induce large endosomes but a functional LI internalization motif was not fundamental for this property. The cytoplasmic tail of Ii is essential for efficient targeting of the class II molecules to endosomes and the dual LI and ML motif may thus be responsible for directing these molecules to the endosomal pathway, possibly via the plasma membrane. PMID- 7983167 TI - The role of transcription factors, chromatin structure and DNA replication in 5 S RNA gene regulation. AB - Differential expression of the oocyte and somatic 5 S RNA genes during Xenopus development can be explained by changes in transcription factor and histone interactions with the two types of gene. Both factors and histones bind 5 S RNA genes with specificity. Protein-protein interactions determine the stability of potentially transcriptionally active or repressed nucleoprotein complexes. A decline in transcription factor abundance, differential binding of transcription factors to oocyte and somatic 5 S genes, and increased competition with the histones for association with DNA during early embryogenesis, can account for the developmental decision to selectively repress the oocyte genes, while retaining the somatic genes in the transcriptionally active state. The 5 S ribosomal genes of Xenopus are perhaps the simplest eukaryotic genes to show regulated expression during development. A large multigene family (oocyte 5 S DNA) is transcriptionally active in oocytes but is repressed in somatic cells, whereas a small multigene family (somatic 5 S DNA) is active in both cell types. A potential molecular mechanism to explain the developmental switch that turns off oocyte 5 S DNA transcription has been experimentally reconstructed in vitro and more recently tested in vivo. Central to this mechanism is the specific association of both transcription factors and histones with 5 S RNA genes. How the interplay of histones and transcription factors is thought to affect transcription, and how their respective contributions might change during development from an oocyte, to an embryo and eventually to a somatic cell is the focus of this review. PMID- 7983166 TI - Lineage-specific regulation of cell cycle gene expression in differentiating myeloid cells. AB - We have analysed the expression of 7 cyclin and cyclin-associated kinase (cdk) genes in the human myeloid cell line HL-60 at different stages of the cell cycle in non-synchronised cells and during terminal differentiation. A clear cell cycle dependent expression was found with cyclins A (S+G2), B (G2) and E (late G1 and S), while other cell cycle genes showed only very weak (cdk2) or no periodic expression (cyclin D1, cyclin D2 and cdk4). Induction of macrophage-like differentiation by TPA or granulocytic differentiation by retinoic acid or DMSO was accompanied by a block in G1 and resulted in distinct patterns of gene expression that were lineage- and inducer-specific. These included: (i) a dramatic decrease in the expression of cyclin A, cyclin B and cdk2, and surprisingly an up-regulation of cyclin D1 in TPA-induced macrophage-like cells; (ii) a down-regulation of cyclin E in retinoic acid-induced granulocytic cells; and (iii) a decreased abundance of cyclin D1 and D2, but high levels of cyclin A, B and E RNA in DMSO-induced granulocytic cells. These observations suggest that the mechanisms leading to a differentiation-associated cell cycle arrest are lineage-specific, and that the sustained expression of cyclin and cdk genes does not interfere with the induction of terminal differentiation. PMID- 7983168 TI - Structural motifs for recognition and adhesion in members of the immunoglobulin superfamily. PMID- 7983169 TI - Microtubules are required in amoeba chemotaxis for preferential stabilization of appropriate pseudopods. AB - Amoebae of Physarum polycephalum exhibit chemotactic responses to glucose and to cAMP. The chemotaxing amoebae exhibit alternating locomotive movements: relatively linear locomotion and movements that change the direction of the locomotion. Such locomotive activity is tightly coupled with the changes in the number and the positions of the pseudopods; cells have one pseudopod at the leading edge during their linear locomotion, while they have multiple pseudopods when they are changing the direction of locomotion. Treatment of cells with microtubule-disrupting reagents inhibited the chemotaxis of the cells. To characterize the role of the microtubule system in chemotaxis, we quantitatively analyzed the relationship between the positions of multiple pseudopods of the amoebae and the relative stability of the pseudopods during reorientation. No significant differences were observed in the pseudopod dynamics between the untreated and the treated amoebae. In both cases, one pseudopod at the leading edge continued to expand during linear locomotion. It then split into two to three pseudopods in the reorientation phase, and the positions of the multiple pseudopods were random. Among multiple pseudopods, however, the pseudopods closer to the microneedle tip were selectively stabilized more often than those distant from the tip in the presence of the microtubule system. By contrast, such preferential stabilization of the appropriate pseudopods was completely abolished by microtubule inhibitors. The microtubule-dependent selection of appropriately located pseudopods enables amoebae to turn correctly at the reorientation step. PMID- 7983170 TI - Identification of coelomocyte unconventional myosin and its association with in vivo particle/vesicle motility. AB - Sea urchin coelomocytes undergo an inducible structural transformation from petalloid to filopodial form during the 'clotting' response in sea urchins. Using a petalloid coelomocyte model, stimulated coelomocytes exhibited bidirectional particle/vesicle motility with a broad distribution of velocities, ranging from 0.02 to 0.12 microns s-1 in the outward bound direction. Coelomocytes treated with the microtubule-disrupting drug, nocodazole, continued to exhibit outward particle/vesicle movements along linear paths with an average velocity of 0.028 +/- 0.006 microns s-1. We partially purified a 110 kDa polypeptide possessing K+EDTA-, Ca2(+)-, Mg2(+)- and F-actin-activated Mg(2+)-ATPase activities characteristic of myosin-like motor proteins. The 110 kDa protein immuno crossreacted with both affinity-purified, anti-brush border unconventional myosin I polyclonal antibodies and anti-Acanthamoeba myosin head monoclonal antibodies. By indirect immunofluorescence, the 110 kDa unconventional myosin was localized to clusters of particles/vesicles within the perinuclear region of unstimulated coelomocytes, an area containing numerous mitochondria, acidic, lysosomal and Golgi organelles. Indirect immunofluorescence of partially transformed and filopodial coelomocytes detected a diminution of perinuclear staining with a concomitant appearance of stained linear arrays of particles/vesicles, enhanced staining of peripheral lamellae, and staining of the entire length of the filopodia. Subfractionation of unstimulated coelomocyte homogenates on linear sucrose gradients identified distinct peaks of ATPase activity associated with fractions containing conventional and 110 kDa unconventional myosin. Unconventional myosin-containing fractions were found to have numerous particles that stained with anti-brush border unconventional myosin-I antibodies and the lipophilic dye, DiOC6. Thus, coelomocytes demonstrate activatable movements of particles/vesicles in cells devoid of microtubules and possess an unconventional myosin, which may be the motor protein driving particle/vesicle translocation. PMID- 7983171 TI - Centrosomal components immunologically related to tektins from ciliary and flagellar microtubules. AB - Centrosomes are critical for the nucleation and organization of the microtubule cytoskeleton during both interphase and cell division. Using antibodies raised against sea urchin sperm flagellar microtubule proteins, we characterize here the presence and behavior of certain components associated with centrosomes of the surf clam Spisula solidissima and cultured mammalian cells. A Sarkosyl detergent resistant fraction of axonemal microtubules was isolated from sea urchin sperm flagella and used to produce monoclonal antibodies, 16 of which were specific- or cross-specific for the major polypeptides associated with this microtubule fraction: tektins A, B and C, acetylated alpha-tubulin, and 77 and 83 kDa polypeptides. By 2-D isoelectric focussing/SDS polyacrylamide gel electrophoresis the tektins separate into several polypeptide spots. Identical spots were recognized by monoclonal and polyclonal antibodies against a given tektin, indicating that the different polypeptide spots are isoforms or modified versions of the same protein. Four independently derived monoclonal anti-tektins were found to stain centrosomes of S. solidissima oocytes and CHO and HeLa cells, by immunofluorescence microscopy. In particular, the centrosome staining of one monoclonal antibody specific for tektin B (tekB3) was cell-cycle-dependent for CHO cells, i.e. staining was observed only from early prometaphase until late anaphase. By immuno-electron microscopy tekB3 specifically labeled material surrounding the centrosome, whereas a polyclonal anti-tektin B recognized centrioles as well as the centrosomal material throughout the cell cycle. Finally, by immunoblot analysis tekB3 stained polypeptides of 48-50 kDa in isolated spindles and centrosomes from CHO cells. PMID- 7983172 TI - Challenge with high concentrations of cyclic AMP induces transient changes in the cytosolic free calcium concentration in Dictyostelium discoideum. AB - Dictyostelium discoideum cells use cyclic AMP (cAMP) for chemotactic signaling as well as for differentiation. The precise regulation of the cytosolic Ca2+ concentration ([Ca2+]i) seems to play a key role for both processes. We performed single cell measurements of [Ca2+]i in amoebae that were starved in suspension for various times and scrape-loaded with the Ca2+ indicator fura-2. Stimulation of cells with cAMP at the concentration required to induce gene expression (> or = 100 microM) elicited a global transient increase in [Ca2+]i that depended on the presence of external Ca2+. Both vegetative and aggregation-competent cells displayed a rise in [Ca2+]i, with aggregation-competent cells responding more often than vegetative cells. Basal [Ca2+]i in the presence of Ca2+ was high in vegetative cells and declined during development; the cAMP-induced rise in [Ca2+]i was higher and lasted longer in vegetative cells than in aggregative cells. The addition of 2'-deoxy-cAMP, which binds to the cAMP receptor, induced an increase in [Ca2+]i, whereas the membrane-permeant analogue 8-bromo-cAMP that has a low affinity for the receptor but activates cAMP-dependent protein kinase had no effect. This indicates that the change in [Ca2+]i is mediated by the cell surface cAMP receptor. Since HC85 mutant cells, which lack the G alpha 2 subunit of the G-protein that couples the receptor to phospholipase C, also responded to stimulation with cAMP, the Ca2+ influx does not seem to be triggered by the phosphoinositide signaling cascade.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7983173 TI - Leishmania donovani-infected macrophages: characterization of the parasitophorous vacuole and potential role of this organelle in antigen presentation. AB - Leishmania donovani amastigotes, the etiological agents of visceral leishmaniasis, are obligate intracellular parasites residing in membrane-bound compartments of macrophages called parasitophorous vacuoles (PV). The study of these organelles is of paramount importance to understanding how these parasites resist the microbicidal mechanisms of macrophages and how they escape the immune response of their hosts. Confocal microscopy of mouse bone marrow-derived macrophages infected with L. donovani amastigotes and stained for various prelysosomal/lysosomal markers and for major histocompatibility complex (MHC) molecules was used to define PV with respect to the endocytic compartments of the host cells and to address the issue of their potential role in antigen processing and presentation. Forty-eight hours after infection, many PV contained cathepsins B, D, H and L and they were all surrounded by a membrane enriched for the lysosomal glycoprotein lgp120/lamp 1 but apparently devoid of the cation independent mannose 6-phosphate receptor, a membrane protein generally absent from the lysosomes. These data suggested that PV acquire within 48 hours the characteristics of a lysosomal compartment. However, both macrosialin and the GTP binding protein rab7p (specific markers of the prelysosomal compartment) were found to be highly expressed in/on PV membrane. Thus, at this stage, PV appear to exhibit both lysosomal and prelysosomal features. Infected macrophages activated with IFN-gamma before or after infection showed PV strongly stained for MHC class II molecules but not for MHC class I molecules. This suggests that, if infected macrophages can act as antigen-presenting cells for class I-restricted CD8+ T lymphocytes, Leishmania antigens must exit the PV. MHC class II molecules reached the PV progressively, indicating that they were not plasma membrane-bound molecules trapped during internalization of the parasites. The redistribution of class II observed in infected cells did not alter their quantitative expression on the plasma membrane at least during the first 48 hours following the phagocytosis of the parasites. The invariant chains, which are transiently associated with class II molecules during their intracellular transport and which mask their peptide-binding sites, did not reach PV or were rapidly degraded in these sites, suggesting that PV-associated class II are able to bind peptides. This last assumption is strengthened by the fact that class II located in PV could bind conformational antibodies that preferentially recognize class II with tightly associated peptides.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 7983174 TI - Visualization and quantification of glycolipid polarity dynamics in the plasma membrane of the mammalian spermatozoon. AB - Seminolipid (sulphogalactosylalkylacylglycerol), the glycolipid that is specific for mammalian germ cells, is located exclusively in the outer leaflet of the sperm plasma membrane. In this study the lateral distribution of seminolipid on sperm heads has been investigated by indirect immunofluorescence labelling and detection with digital imaging fluorescence microscopy. In freshly ejaculated sperm cells this glycolipid was present primarily at the apical ridge subdomain of the plasma membrane of the sperm head. After binding the sperm cells to zona coated coverslips seminolipid migrated, in 40 minutes, from the apical ridge to the equatorial subdomain of the plasma membrane. A similar redistribution of seminolipid was observed during capacitation of sperm cells in vitro induced by Ca2+ or bovine serum albumin. Comparable migration of seminolipid was also found after prolonged storage of ejaculated sperm cells, albeit at a much slower rate. Addition of arylsulphatase A, an enzyme present in seminal plasma that desulphates seminolipid, significantly enhanced the migration of seminolipid during storage of sperm cells. Its breakdown product desulphoseminolipid (galactosylalkylacylglycerol) appeared highly specifically at the equatorial segment. The measured fluorescence intensity over the sperm head surface correlated linearly with the spatial probe distribution as was checked by fluorescence lifetime imaging microscopy. This paper demonstrates and quantifies for the first time the polarity of seminolipid on the surface of the sperm cell and the dynamic alterations that occur in this polarity during post-ejaculatory events. PMID- 7983175 TI - Mutations in the Caenorhabditis elegans beta-tubulin gene mec-7: effects on microtubule assembly and stability and on tubulin autoregulation. AB - We have sequenced 45 mutations in mec-7, a beta-tubulin gene required for the production of 15-protofilament microtubules in the nematode Caenorhabditis elegans, and have correlated sequence alterations with mutant phenotypes. The expression patterns of most alleles have also been determined by in situ hybridization and immunocytochemistry. Most (12/16) complete loss-of-function alleles, which are recessive, result from nonsense mutations, insertions, or deletions; three others disrupt a putative GTP-binding domain. Three of the four loss-of-function, missense mutations result in elevated mec-7 message levels, suggesting a defect in tubulin autoregulation that may be attributable to a loss in the ability to form heterodimers. Most (8/9) mild alleles are caused by missense mutations. Two mild alleles appear to increase microtubule stability and lead to the elaboration of ectopic neuronal processes in mec-7-expressing cells. Most (15/23) mutations that cause severe dominant or semidominant phenotypes are clustered into three discrete domains; four others occur in putative GTP-binding regions. Many of these dominant mutations appear to completely disrupt microtubule assembly. PMID- 7983176 TI - Quantification of low density lipoprotein and transferrin endocytic sorting HEp2 cells using confocal microscopy. AB - Numerous experiments on CHO cells have shown that endosomes are composed of separate vesicular and tubulovesicular compartments, such as the sorting endosome, the recycling compartment, and the late endosome. However, Hopkins et al. (Nature 346, 335-339, 1990) have reported that endosomes in HEp2 human carcinoma cells form an extensive tubular reticulum. To resolve their observations with previous results from CHO and other cells, we examined the sorting and intracellular transport of endocytosed macromolecules in HEp2 cells, using low density lipoprotein (LDL) and transferrin (Tf) to probe the lysosomally directed and recycling pathways, respectively. Fluorescent LDL and Tf were observed with laser scanning confocal microscopy to visualize simultaneously both probes' sorting and subsequent post-sorting behavior in HEp2 cells. Quantifying the 3-dimensional cellular distributions of fluorescent LDL and Tf, after a variety of pulsechase schemes, gave the ligands' trafficking rates. Initially, both ligands appear in the same punctate sorting endosomes, and fingers of Tf start extending from these sorting endosomes. Tf rapidly leaves dual-labeled sorting endosomes (t1/2 approximately 2.5 minutes) and enters a post-sorting recycling compartment from which it is recycled out of the cell (t1/2 approximately 7 minutes). We present both morphological and kinetic data supporting the existence of these two separate compartments along the recycling pathway in HEp2 cells. LDL remains in punctate sorting endosomes that eventually lose the ability to receive newly endocytosed LDL, and mature into late endosomes. The trafficking and sorting of Tf and LDL in HEp2 cells follow the same general scheme as in CHO cells, indicating that the tubular endosomes previously seen may be the tubular parts of the sorting endosomes and recycling compartments in these cells. We propose that the endosomes in the recycling pathway of HEp2 cells, as in CHO cells, are composed of short-lived sorting endosomes, accessible to both Tf and LDL, and long-lived post-sorting recycling compartments, which contain Tf and recycling receptors but not LDL. PMID- 7983177 TI - Replication factories and nuclear bodies: the ultrastructural characterization of replication sites during the cell cycle. AB - Sites of replication in synchronized HeLa cells were visualized by light and electron microscopy; cells were permeabilized and incubated with biotin-16-dUTP, and incorporation sites were immunolabelled. Electron microscopy of thick resinless sections from which approximately 90% chromatin had been removed showed that most DNA synthesis occurs in specific dense structures (replication factories) attached to a diffuse nucleoskeleton. These factories appear at the end of G1-phase and quickly become active; as S-phase progresses, they increase in size and decrease in number like sites of incorporation seen by light microscopy. Electron microscopy of conventional thin sections proved that these factories are a subset of nuclear bodies; they changed in the same characteristic way and contained DNA polymerase alpha and proliferating cell nuclear antigen. As replication factories can be observed and labelled in non-permeabilized cells, they cannot be aggregation artifacts. Some replication occurs outside factories at discrete sites on the diffuse skeleton; it becomes significant by mid S-phase and later becomes concentrated beneath the lamina. PMID- 7983178 TI - Mammalian cells have two functional RCC1 proteins produced by alternative splicing. AB - Previously we cloned two human RCC1 cDNAs that differed in their noncoding region. In this study, we have found new human and hamster RCC1 cDNAs, which have an even more different coding region from that of the previously cloned RCC1 cDNAs yet can complement the RCC1 mutation in the tsBN2 cell line. The newly found RCC1 cDNAs encode a protein (designated as RCC1-I) that has an insertion of 31 (human) and 13 (hamster) amino acids at valine25 in the N-terminal region outside the RCC1-seven repeat. The inserted nucleotide sequence was searched for, within the human RCC1 genomic sequence that had already been determined, and was found to be located between the 6th and 7th exons, designated as the 6' exon. Both the 5' and 3' ends of the 6' exon correspond to the GT-AG rules for splicing, indicating that human RCC1-I mRNAs are produced by alternative splicing. The finding that both humans and hamsters have the insertion at the same RCC1 site suggests that the pattern of alternative splicing in the RCC1 gene has been conserved through evolution. PMID- 7983179 TI - Regulation of chemical stress-induced hsp70 gene expression in murine L929 cells. AB - We have investigated the regulation mechanism of chemical stress-induced hsp70 gene expression in murine L929 cells. Our data show that chemical treatments including sodium arsenite, cadmium chloride and sodium salicylate, induced significant synthesis of hsp70 and its mRNA. The induced hsp70 gene expression appears to be regulated at the transcriptional level. A factor (CHBF), which constitutively binds to the heat shock element (HSE) at 37 degrees C, functions like a negative regulator and the heat-induced heat shock factor (HSF) acts as an activator. The chemical treatments that induce significant hsp70 synthesis activate HSF binding to HSE but also dissociate the HSE-CHBF complex. Some chemical treatments, e.g. IPTG, which fail to activate hsp70 gene transcription, still activate HSF binding to HSE. However, in this case, the HSE-CHBF complex remained like that of untreated control cells. PMID- 7983181 TI - Cell kinetic characterization of growth arrest in cultured human keratinocytes. AB - In this study we have performed a cell kinetic characterization of growth and growth arrest of keratinocytes derived from normal human skin. Proliferative activity of the cell cultures was analysed with a flow cytometric technique, measuring relative DNA content and iododeoxyuridine (IdUrd) incorporation simultaneously. Normal human keratinocytes were grown in keratinocyte growth medium (KGM) and growth arrest was induced by using either keratinocyte basal medium (KBM) or KGM supplemented with TGF-beta 1. It was found that human keratinocytes grown in KGM plus TGF-beta 1 were growth-arrested within 52 hours. The rate of IdUrd incorporation into DNA decreased by more than 95% after 52 hours and paralleled the decrease of cells in S-phase. Within 52 hours after addition of TGF-beta 1, 79% of the growth-arrested cells were in the G0/G1-phase of the cell cycle, a situation that approaches that of the normal epidermis. Growth arrest of human keratinocytes in KBM showed a similar decrease in the rate of IdUrd incorporation. However, the decrease in IdUrd incorporation was not reflected in a decrease in cells in S-phase, suggesting that the cells were blocked in G0/G1, S or G2/M-phase rather than selectively in the physiological growth arrest state of G0/G1. Secondly, we investigated the kinetics of the cells when they were restimulated after growth arrest. We found that after termination of the growth arrest in KGM supplemented with TGF-beta 1 the cells require 6 to 8 hours to initiate DNA synthesis, with a continued decrease in the G0/G1 population, suggesting that the cells are recruited as a cohort. After growth arrest induced by KBM, cells also require 6 to 8 hours in KGM to initiate DNA synthesis, but the cells are not recruited as a cohort. We conclude that growth arrest induced by TGF-beta 1 is the preferred system in which to study induction of keratinocyte proliferation, since it induces a state of quiescence that approaches that of normal human epidermis. PMID- 7983180 TI - Expression of prelamin A but not mature lamin A confers sensitivity of DNA biosynthesis to lovastatin on F9 teratocarcinoma cells. AB - The role of inhibition of prelamin A processing in the inhibition of DNA synthesis by lovastatin was examined by expressing prelamin A in F9 teratocarcinoma cells. These cells, normally lacking expression of the A/C lamins, were transfected with constructs expressing either prelamin A or mature lamin A and the effect of lovastatin on DNA biosynthesis was assessed. It was found that expression of prelamin A specifically conferred sensitivity to inhibition of DNA biosynthesis by lovastatin on F9 cells. PMID- 7983182 TI - Intracellular free calcium oscillations in normal and cleavage-blocked embryos and artificially activated eggs of Xenopus laevis. AB - We have measured levels of intracellular free calcium ([Ca2+]i) in albino Xenopus laevis embryos using recombinant aequorin and a photon-counting system. We observed sinusoidal oscillations in [Ca2+]i that had the same frequency as cleavage, with cleavage occurring when [Ca2+]i was lowest. An increase in calcium was seen to precede first cleavage. The cyclic changes in calcium were superimposed on a secondary pattern that increased, peaked between third and fifth cleavages and then slowly declined to a level similar to that measured before first cleavage. The amplitude of the oscillations was small during the first few cleavages but became larger with each cycle, with the largest oscillations occurring when the secondary pattern peaked (between third and fifth cleavage). As the secondary pattern declined, the amplitude of the oscillations also became smaller. The oscillations are due to release of calcium from intracellular stores, since the signal was the same in calcium-free solution as in normal medium. When cleavage was blocked with the microtubule-disrupting drugs colchicine or nocodazole, the [Ca2+]i oscillations persisted. Calcium oscillations of a similar magnitude and frequency were also present in artificially activated eggs. The secondary pattern was different in cleavage blocked embryos and artificially activated eggs, the baseline increasing until about the third cycle and then remaining elevated for the rest of the recording (> 8 hours). By fixing embryos at various points in the calcium cycle, we determined that mitosis began shortly after calcium levels reached their peak and was complete before the calcium level dropped to its lowest point.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7983183 TI - Isolation and characterization of a sea urchin zygote cortex that supports in vitro contraction and reactivation of furrowing. AB - The isolation of the cortex of the sea urchin blastomere by detergent lysis was explored with the aim of analyzing components important in the structure and function of the cortical cytoskeleton, and their relationship to such phenomena as contraction. Buffered EGTA medium supplemented with isotonic glycerol and with magnesium, at a level close to the reported internal cellular concentration, yields stable cytoskeletal cortices that retain their spherical shape. Cortices prepared this way contain actin, myosin, fascin and spectrin, components normally associated with the cortical cytoskeleton in a similar distribution to that in intact zygotes. They retain the organized cortical filamentous structure, including the actin-fascin bundles that form cores of microvilli. ATP and NaCl caused changes in cortical shape, described as either contraction or expansion, respectively. Spectrin, but not myosin, was partially extracted by NaCl, resulting in expansion of the cortex that suggests a role for spectrin in maintenance of cortical structure. ATP (but not ADP nor ATP gamma S), which caused the partial removal of myosin and spectrin, led to the contraction of the cortex, consistent with a role for myosin in cortical tension. In cortices isolated from dividing eggs, the zygotes retained their cleavage furrows and ATP induced continuation of furrow progression. This preparation appears to be a useful in vitro model for cytokinesis. PMID- 7983184 TI - Isolation of polypeptides with microtubule-translocating activity from phragmoplasts of tobacco BY-2 cells. AB - As part of our efforts to understand the molecular basis of the microtubule associated motility that is involved in cytokinesis in higher plant cells, an attempt was made to identify proteins with the ability to translocate microtubules in an extract from isolated phragmoplasts. Homogenization of isolated phragmoplasts in a solution that contained MgATP, MgGTP and a high concentration of NaCl resulted in the release from phragmoplasts of factors with ATPase and GTPase activity that were stimulated by microtubules. A protein fraction with microtubule-dependent ATPase and GTPase activity caused minus-end headed gliding of microtubules in the presence of ATP or GTP. Polypeptides with microtubule-translocating activity cosedimented with microtubules that had been assembled in vitro from brain tubulin and were dissociated from sedimented microtubules by addition of ATP or GTP. After cosedimentation and dissociation procedures, a 125 kDa polypeptide and a 120 kDa polypeptide were recovered in a fraction that supported minus-end-headed gliding of microtubules. The rate of microtubule gliding that was caused by the fraction that contained the 125 kDa and 120 kDa polypeptides as main components was 1.28 microns/minute in the presence of ATP and 0.50 microns/minute in the presence of GTP. This fraction contained some microtubule-associated polypeptides in addition to the 125 kDa and 120 kDa polypeptides, but a fraction that contained only these additional polypeptides did not cause any translocation of microtubules. Thus, it appeared that the 125 kDa and 120 kDa polypeptides were responsible for translocation of microtubules. These polypeptides with plus-end-directed motor activity may play an important role in formation of the cell plate and in the organization of the phragmoplast. PMID- 7983185 TI - Apical plasma membrane proteins are not obligatorily stored in secretory granules in exocrine cells. AB - Exocrine cells are epithelial cells in which secretory granules undergo fusion with the apical plasma membrane upon secretagogue stimulation. Several apical plasma membrane proteins have been found in secretory granules in cells from pancreas and salivary glands raising the possibility that incorporation into secretory granules followed by exocytosis of the granules accounts for their insertion into the apical plasma membrane. To test this hypothesis, we have expressed the influenza hemagglutinin (HA) in pancreatic AR42J cells, which make zymogen-like granules upon incubation with dexamethasone. The influenza virus HA is known to be specifically targeted to the apical plasma membrane of epithelial cells that lack a regulated pathway and is also known to be excluded from secretory granules in virally-infected pituitary AtT20 cells. Localization of the protein by immunofluorescence microscopy revealed that it accumulated at the plasma membrane of the transfected AR42J cells. HA was not observed in the amylase-rich secretory granules. By immunolabeling of ultrathin cryosections of the transfected cells, HA was also found exclusively on the cell surface, with label over secretory granules not exceeding that seen in control, untransfected cells. In addition, in cell fractionation experiments performed on radiolabeled AR42J cell transformants, HA was not detectable in the secretory granule fractions. These results indicate that HA is not efficiently stored in mature secretory granules and is likely to reach the cell surface via constitutive transport pathways. PMID- 7983187 TI - Dermal fibroblasts activate keratinocyte outgrowth on collagen gels. AB - The effects of dermal fibroblasts on keratinocyte outgrowth on collagen substrata was studied using an in vitro keratinocyte-collagen gel composite model. Skin fibroblasts were seeded inside collagen gels, which remained attached to the cell culture plastic substratum. Fibroblasts incorporated in collagen gels were either kept viable throughout the study, or were lysed hypotonically with water at different time intervals (2 hours and 5 days). Results show that very little keratinocyte outgrowth occurred on either plain collagen gels or gels that had previously contained viable fibroblasts for 2 hours. A 3- to 4-fold increase in keratinocyte outgrowth occurred on collagen gels that had previously contained viable fibroblasts for 5 days. A striking increase (20-fold) in keratinocyte outgrowth was observed on collagen gels that contain viable fibroblasts. The effect of fibroblast diffusible factors on keratinocyte outgrowth was further studied with a co-culture system using Millicell inserts. It was found that the co-culture of fibroblasts with the composite enhanced keratinocyte outgrowth on collagen gels that had previously contained viable fibroblasts for 5 days. Among all, however, the keratinocyte outgrowth was far better on gels containing viable fibroblasts. Addition of keratinocyte growth factor or its neutralizing antibody did not affect keratinocyte outgrowth. These results suggest that dermal fibroblasts can activate keratinocyte outgrowth on collagen matrices through some diffusible factors other than keratinocyte growth factor, and epithelial mesenchymal interactions exert some special effects on keratinocyte outgrowth on collagen gels. PMID- 7983186 TI - Differential calmodulin binding to three myosin-1 isoforms from liver. AB - We have previously purified and characterized two myosin-1 isoforms from rat liver (molecular masses 130 kDa and 110 kDa; L. M. Coluccio and C. Conaty (1993) Cell Motil. Cytoskel. 24, 189-199). Here, we describe the purification and characterization from liver of a third myosin-1 (molecular mass 105 kDa) and determine the number of calmodulin molecules associated with each of these three myosin-1 isoforms. The 105 kDa polypeptide, solubilized from liver homogenates with the addition of ATP, co-sediments with F-actin, co-purifies with calmodulin, and binds calmodulin in the presence of EGTA. Antibodies directed against chicken intestinal brush border myosin-1 cross-react with the 105 kDa polypeptide on immunoblots. Partial peptide sequence analysis indicates that the polypeptide corresponds with an MM1 gamma gene product that represents a myosin-1 isoform cloned from mouse brain (Sherr et al. (1993) J. Cell Biol. 120, 1405-1416). A comparison of calmodulin binding to the now three isolated forms of myosin-1 in liver shows that in solution the 105 kDa and 110 kDa polypeptides bind two molecules of calmodulin each whereas the 130 kDa binds six molecules of calmodulin. PMID- 7983188 TI - The endless story of the glial fibrillary acidic protein. AB - All intermediate filament proteins consist of an alpha-helical rod domain flanked by non-helical N-terminal head and C-terminal tail domains. The roles of the non helical domains of various intermediate filament proteins in the assembly and co assembly of higher-order filamentous structures have been studied by many groups but with quite contradictory results. Type III intermediate filaments are unique in that they can form homopolymers both in vitro and in vivo. The expression and assembly characteristics of carboxy- and amino-terminal deletion mutants of glial fibrillary acidic protein (GFAP), an astrocyte-specific type III intermediate filament protein, were examined by transient transfections of either vimentin positive or vimentin-negative variants of human adrenocarcinoma-derived SW13 cell lines. Whereas complete deletion of the C-terminal tail domain of GFAP results in the formation of polymorphic aggregates, both intranuclear and cytoplasmic in self-assembly experiments, efficient co-assembly of these tail-less GFAP mutants with vimentin can be achieved as long as the KLLEGEE sequence at the C-terminal end of the rod domain is preserved. Up to one-fifth of the C-terminal end of the tail domain can be deleted without affecting the capability of GFAP to self assemble. The highly conserved RDG-containing motif in the tail domain may be important for self-assembly but is not sufficient. The entire head domain seems to be required for self-assembly. All N-terminal deletion mutants of GFAP share the same phenotype of diffuse cytoplasmic staining when expressed in vimentin negative SW13 cells. Although co-assembly with vimentin can still be achieved with completely head-less GFAP, preservation of some of the head domain greatly enhanced the efficiency. Our results form the basis for further, more detailed mapping of the essential regions in filament assembly of GFAP and other type III IFs. PMID- 7983190 TI - National health care reform minus public health: a formula for failure. AB - Universal access to medical services will not address all important health needs. Impending health care reform, guided by public health strategies, could achieve many previously unattainable health goals. However, such a public health role seems unlikely. Public health reaches beyond the current popular notion of prevention focused on individual lifestyle, yet attention to public health authority has waned. The history of immunization, a personal health service effective only within a public health strategy, illustrates the dilemma. Britain required 40 years of National Health Service before it invoked a public health strategy to assure effective immunization. Reformed health care must perform certain functions systematically that in the past were optional for medical practitioners or left to health departments by default. Reformers must rebuild public health authority in states, to assure that medical services we will pay for under health care reform accomplish functions critical to the health of the public. PMID- 7983189 TI - SKALP/elafin is an inducible proteinase inhibitor in human epidermal keratinocytes. AB - Skin-derived antileukoproteinase (SKALP), otherwise known as elafin, is a recently discovered epidermal proteinase inhibitor with specificity for polymorphonuclear leukocyte (PMN)-derived elastase and proteinase-3; in addition to the proteinase-inhibiting domain, SKALP contains several transglutaminase substrate motifs. SKALP is virtually absent in normal human epidermis but is found in a number of inflammatory skin diseases, including psoriasis. Here we report the induction and processing of SKALP in vivo and in vitro. SKALP expression in vivo could be demonstrated following injury in normal human epidermis, using histology, western blotting, northern blotting and a functional assay. In vitro, SKALP expression was studied in conventional submerged keratinocyte culture systems and in keratinocytes cultured in an air-liquid interface model. Induction of SKALP activity in epidermis could be measured as early as 16 hours after skin injury; immunohistological examination showed that SKALP expression was confined to the outer layers of the stratum spinosum and the stratum granulosum. Northern blot analysis revealed a 0.8 kb transcript, both in vivo (psoriatic skin, injured skin) and in vitro (cultured keratinocytes). Western blot analysis showed that the major SKALP form in vivo was a low molecular mass fragment, containing the antiproteinase domain. In all cultures that were positive for SKALP, larger (8-10 kDa) forms of SKALP, containing the N terminal transglutaminase substrate motifs in addition to the antiproteinase domain, were found. SKALP expression in cultured cells was found to be dependent on the system used. In a submerged culture system, SKALP could be induced by fetal calf serum.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7983191 TI - The dynamics of health care organisation in Britain. AB - The National Health Service provides a 'policy puzzle' to British governments: how to cope with rising demands in a service which is extremely popular with the public, whilst maintaining economic orthodoxy with regard to public expenditure. The limited number of options for reconciling these tensions has provided the menu from which successive recent policies for organising and managing the Service have been drawn, and from which governments will continue to have to choose over the next few years. PMID- 7983192 TI - Causal debates in environmentalism. AB - Many public health policy analysts celebrate the renewed popularity of environmentalism and its importance for public health. But few recognize that there are three competing versions of environmentalism. Each one assigns blame for environmental degradation and responsibility for addressing it to a different group of people. It is incumbent upon public health professionals to take note of the debate and to consider the ramifications for policy should one of these versions come to predominate. PMID- 7983193 TI - Restrictions on smoking: growth in population support between 1983 and 1991 in Ontario, Canada. AB - While much progress in curtailing exposure to environmental tobacco smoke has occurred in Ontario, many jurisdictions still do not have any restrictions on smoking. To assess support in Ontario for restrictions, and recent changes in knowledge, attitudes, and behavior, we compared the findings of a population based telephone survey conducted in 1991 (n = 1421) to those of a similar survey conducted in 1983 (n = 1383). Increases were found in the population's reported knowledge of specific health effects. Marked changes occurred in attitudes to restrictions on smoking. In 1991, the population consistently favoured more restrictions on smoking and their enactment by all levels of government. A role for local health departments in enforcement was clearly recognized. Most smokers indicated that they would comply with more restrictions. We also found that the self-reported prevalence of smoking had decreased 8 percentage points between 1983 and 1991. Population-based evidence of strong and increasing support for restrictions, accompanied by predictions of a high level of compliance, especially by smokers themselves, should facilitate legislation aimed at further curtailing smoking. PMID- 7983194 TI - Creating an agenda for research and evaluation: HIV service delivery, the Ryan White CARE Act, and beyond. AB - HRSA, AHCPR and NCAP convened a working meeting in November 1992, to discuss creation of a national agenda for research and evaluation on HIV service delivery systems that are cost-effective, responsive to the needs of the diverse populations affected by the epidemic, and reflective of the lessons learned so far. In this article, the interests and goals of the conveners are described, the meeting's process and outcomes are discussed, and the nine key study areas that were identified and chosen by the meeting participants are presented. It is hoped that this article will stimulate further interest among private and public funders and among the research community in fostering the implementation of HIV service delivery-related research and evaluation studies. If this is accomplished, decision-makers will be better enabled to make informed and responsive policy decisions. PMID- 7983195 TI - Genetic discrimination and screening for hemochromatosis. AB - Recent advances in tests for the genotype for hemochromatosis and suggestions that the tests be used in mass screening programs for the disease raise the possibility of a large increase in the incidence of discrimination against people who are found to be homozygous for hemochromatosis. This paper presents cases of genetic discrimination drawn from a study of discrimination against people with a variety of genetic conditions. The cases discussed here involve employment and several types of insurance discrimination against people diagnosed with hemochromatosis who either are currently asymptomatic or whose condition is controlled by means of phlebotomies. There is no justification for these types of discrimination since people with controlled hemochromatosis suffer no excess mortality or morbidity. Our study suggests that genetic discrimination is already a serious problem and that any proposed screening program for hemochromatosis or other genetic condition must consider and attempt to mitigate its effects. PMID- 7983196 TI - Sense of coherence: its effects on psychological and physiological processes prior to, during, and after a stressful situation. AB - This study examined whether Antonovsky's (1987) stress-resistance construct, sense of coherence (SOC), affected individuals' psychological and/or physiological responses to a controlled stressful situation. Subjects were assessed for SOC level and then completed a battery of questionnaires before and after a stressful situation. Physiological responses were monitored during baseline, anticipation, and recovery periods. Analyses examined differences among low, middle, and high SOC groups and revealed group differences in psychological distress, cognitive appraisal, coping processes, and pulse rate. These results provide some support for the validity and utility of Antonovsky's SOC construct by indicating that low SOC subjects show more distress and appraise and cope with stressful situations in ways less likely to resolve or eliminate their distress. PMID- 7983197 TI - Psychosocial variables that affect the psychological adjustment of IVDU patients with AIDS. AB - The influences of coping strategies and of perceived social support from family and friends on the psychological adjustment of intravenous drug users (IVDUs) with Acquired Immunodeficiency Syndrome (AIDS) were investigated. Twenty-seven male AIDS patients with a history of intravenous drug use completed a demographic questionnaire, Trails-B, the Ways of Coping Questionnaire, Perceived Social Support from Family, Perceived Social Support from Friends, and the Mental Health Inventory. Unexpected results were obtained: The only coping strategy to correlate significantly with psychological adjustment was "Seeking Social Support," and perceived social support from family correlated positively with psychological adjustment, but perceived social support from friends did not. Interpretations and implications of these findings are presented. PMID- 7983198 TI - Cluster analysis of MCMI and MCMI-II on chronic PTSD victims. AB - A cluster analysis was used to identify groups of inpatients with confirmed post traumatic stress disorder (PTSD) due to combat. In Study 1 the MCMI was administered to 256 subjects, in addition to the MMPI, PTSD measures, and background variables. Three clusters resulted: a Traumatic Personality (8-2), Schizoid Influence (8-2-1), and Antisocial Influence (8-6). Comparison on the MCMI symptom scales, MMPI, and PTSD scales showed that the Antisocial Influence cluster was "healthier" on all measures. The Schizoid Influence was most psychopathological. In Study 2 the MCMI-II was administered to 136 new subjects who met the same criteria as in Study 1. Four clusters resulted: Global (1-2-6A 6B-8A-8B), Subclinical (1), Aggressive (6A-6B-8A), and Detached/Self-defeating (1 2-8A-8B). PMID- 7983199 TI - Preliminary development of a questionnaire designed to measure neurotic perfectionism in the eating disorders. AB - The preliminary development and validation of a new self-report questionnaire (the NPQ) for measuring neurotic perfectionism in the eating-disorder population is described. The 42-item instrument demonstrated satisfactory internal consistency. All test items correlated significantly with both SCANS P and SCANS D (subscales of the SCANS [Slade & Dewey, 1986]), thus indicating neurotic perfectionism according to Slade, Newton, Butler, and Murphy (1991), and discriminated well between controls and eating-disorder patients. NPQ scores demonstrated significant group differences on comparison of neurotic perfectionists with normal and non-perfectionists (defined by the SCANS) and with subjects who scored above the EAT-26 (Garner, Olmsted, Bohr, & Garfinkel, 1982) subscale cut-offs when compared with those who scored below. PMID- 7983200 TI - Relationships among clinical and validity scales of the Basic Personality Inventory. AB - In interpreting the results of a self-report inventory it is important to evaluate the extent to which stylistic distortion may have been operative. This task is complicated because validity measures frequently are confounded with content measures. In order to evaluate the potential utility of the validity measures for the Basic Personality Inventory (BPI) the relationships between validity measures and content scales were evaluated in a sample of 71 inmates. While some validity indices had significant correlations with content scales, other validity indices were relatively independent of the content scales. Recommendations are provided for using the BPI validity scales. PMID- 7983201 TI - MMPI profiles in PTSD as a function of comorbidity. AB - A sample of 135 Vietnam veteran inpatients with combat-related PTSD was sorted into three groups, depending upon the presence of concurrent psychiatric disorders: Depression (n = 68), Psychosis (n = 31), and Other (n = 36). Pairwise comparisons were made on the MMPI with respect to the validity indicators, clinical scales, four relevant Harris-Lingoes subscales, the Psychoticism content scale, and the MMPI-PTSD subscale. Results indicate variations in scale elevations as a function of comorbid diagnosis. Various items and scales appear to differentiate the Psychosis group due to greater psychopathology. In general, the results spotlight the heterogeneous aspects that comorbidity brings to PTSD assessment. PMID- 7983202 TI - An analysis of the relationship of gender and age to MMPI scores of patients with chronic pain. AB - This study investigated the relationship of age and gender to the MMPI scores of patients with chronic pain; 1,766 patients with musculoskeletal lumbar and/or cervical pain were evaluated, using the MMPI. Multivariate analysis of variance (p < .001) revealed main effects for gender and age group variables; no interaction effects were found. For the age group variable, significant differences were found on two validity and seven clinical scales. Subjects in the 70- to 90-year age group produced the lowest scores on all scales except L, F, and MF. Linear declines across age groups, and quadratic effects were found on some scales. The authors hypothesize that developmental transitions may account in part for these findings. PMID- 7983203 TI - The Brief Symptom Inventory (BSI) as an outcome measure for adult psychiatric inpatients. AB - In this study the Brief Symptom Inventory (BSI; Derogatis & Spencer, 1982) was administered to 89 males and 128 females at admission and discharge from a private psychiatric hospital. For mean scores, statistically significant decreases were observed on all BSI scales and global indices. Effect sizes ranged from high medium to large. Also, when clinical significance indices were calculated with regard to changes made by individual patients, we found that approximately 50% of all inpatients evidenced a decrease on the Global Severity Index (GSI), which meets the dual criteria of significant change and posttreatment functioning in the normal range. Compared with inpatient norms (Derogatis & Spencer, 1982), our sample generally scored higher at admission and lower at discharge. PMID- 7983204 TI - A Self-Rated Scale for Obsessive-Compulsive Disorder. AB - The Self-Rated Scale for Obsessive-Compulsive Disorder is an objective 35-item questionnaire that measures the severity of obsessive-compulsive disorder (OCD). Scale construction employed both rational and empirical item-selection procedures and utilized the responses of 127 diagnosed obsessive-compulsive subjects. A cross-validation study that used 40 obsessive-compulsive subjects found high internal consistency and significant correlations between the new scale and two clinician-rated measures of OCD. Principal components analysis of the combined subject sample (167 obsessive-compulsive subjects) identified four orthogonal components: distressing thoughts, rituals, perfection, and fear of contamination. In conclusion, the Self-Rated Scale for Obsessive-Compulsive Disorder appears to be a comprehensive, easy-to-use, and psychometrically sound instrument for measuring severity of OCD. PMID- 7983205 TI - Validating Antonovsky's Sense of Coherence Scale. AB - This study empirically supported Antonovsky's predictions that a person's Sense of Coherence is implicated in coping with life stresses and psychological distress. Sense of Coherence scales accounted for as much variance in criterion measures of Life Events stressors, Depression, and Anxiety as did traditional locus of control and social support predictor measures. Sense of Coherence scales emerged as useful additions for studies of personality characteristics implicated in personal reactions to distressing life events. PMID- 7983206 TI - A comparison of MMPI and MMPI-2 in PTSD assessment. AB - A sample of 47 Vietnam veterans with the diagnosis of combat-related Post Traumatic Stress Disorder (PTSD) was administered the MMPI and MMPI-2. Pairwise comparisons were performed on the clinical scales, Harris Lingoes subscales, and scales relevant to the assessment of PTSD. Correlational analyses were performed as well. Hit rates of high-point pairs were compared across the tests. The results suggest a high degree of congruence between tests. Differences were seen on evaluations of some scales between tests that may influence interpretation and treatment. PMID- 7983207 TI - Emotional correlates of fluency test and maze performance. AB - This study tested the hypothesis that depression, anxiety, and bizarre thought content, as measured by MMPI-2 scales, would show a negative relationship with performance on widely used measures of executive functioning. Subjects were 70 male psychiatric patients who were ostensibly free of any neurologic disease or history of substance abuse. Correlational analyses were performed between age and education-corrected scores on the Controlled Oral Word Association Test (FAS), Design Fluency, and WISC-R Mazes, and scores on MMPI-2 scales D, PT, Anxiety, Fears, Obsessional Thinking, Depression, and Bizarre Mentation. The findings suggest that fluency and maze performance is (1) largely independent of measures of depression (D, DEP) and bizarre mentation (BIZ); (2) mildly associated with a measure of generalized anxiety (ANX); and (3) strongly related to an MMPI-2 measure of fearfulness (FRS). PMID- 7983208 TI - The pattern of deficit in different memory components in normal aging and dementia of Alzheimer's type. AB - The study explored differential patterns of deficits in different memory components as a function of dementia severity. Three groups of 58 subjects each were used: (1) highly functioning elderly who are free of neurological or psychiatric symptoms; (2) individuals with early signs of memory disturbance, whose MMSE scores were > or = 24; and (3) individuals with MMSE scores below 24, who meet criteria for DAT. Performance on the tests that assess different memory components was compared for the three groups. Results suggest pronounced change in acquisition component of memory at the onset of dementia, whereas retrieval from remote memory discriminates well between the mild and the more advanced phases of the disease. Retrieval from recent memory deteriorates more gradually. Based on these results, efficiency of different memory mechanisms was discussed. PMID- 7983209 TI - Construct validity of neuropsychological tests of conceptual and attentional abilities. AB - In a mixed sample of community-living adults, this study examined the construct validity of five neuropsychological tests: Category Test (CAT), Wisconsin Card Sorting Test (WCST), Paced Auditory Serial Addition Task (PASAT), Visual Search and Attention Test (VSAT) and Trail Making Test: Part B (TMT-B). Principal components analyses showed that PASAT, VSAT, and TMT-B defined an attention factor and that CAT and WCST defined a conceptual factor. The results were discussed in terms of common interpretations of these procedures as well as in terms of Mirsky's (1989) components of attention. PMID- 7983210 TI - Assessment of motivation and memory with the Recognition Memory Test after financially compensable mild head injury. AB - Warrington's Recognition Memory Test (RMT) was used in the assessment of memory and motivation in a study of 63 adult subjects. Subjects reporting mild head trauma who claimed disability and were seeking financial compensation (MT-Comp) obtained significantly lower scores on both subtests of the RMT than subjects with moderate and severe brain trauma (ST) and subjects with mild head injuries who had returned to work (MT-Work). Of the MT-Comp, 47% and 29% scored below chance on the Faces and Words subtests, respectively, compared to 10% and 6% in ST group and 0% and 0% in the MT-Work group. A discriminant function that consisted of both RMT subtests discriminated between the MT-Work and MT-Comp groups with an overall accuracy of 93%. PMID- 7983211 TI - Head injury and the Satz-Mogel type short form WAIS-R. AB - The current study investigated the efficacy of a Satz-Mogel type short form of the WAIS-R in a closed head injury (CHI) population and whether the short form's effectiveness varied by lesion site. Data were taken from the files of 79 CHI patients, 20 with left hemisphere damage, 15 with right hemisphere damage, 29 with bilateral damage, and 15 with only diffuse damage. Information about IQ scores and age-corrected subtest scores was examined. As expected, correlations between two forms, for both IQ scores and subtest scores were high. However, there was a remarkable percentage of deviation in scaled score points and changes in intellectual classification for some of these scores. No evidence was found to support the notion that usefulness of the short form varied according to the location of lesion. PMID- 7983212 TI - Rater agreement for the Rey-Osterrieth Complex Figure Test. AB - This report assesses the intrarater and interrater reliability of quantitatively scoring the Rey-Osterrieth Complex Figure Test (RCF). The intrarater correlation coefficients were .96, .99, and .96, and the interrater correlation coefficients were .88, .97, and .96 for the Copy, Immediate Recall, and Delayed Recall, respectively. However, statistically significant mean differences in score were found between raters on the Copy, Immediate, and Delayed Recall. Though the majority of structural units within the RCF are reliably scored, several units had a greater magnitude of observed scoring differences compared to the other units after adjusting for expected differences. Overall, reliability estimates demonstrate high intrarater reliability and acceptable interrater reliability except for the potential for systematic scoring differences. PMID- 7983213 TI - Lay theories of psychotherapy and perceptions of therapists: a replication and extension of Furnham and Wardley. AB - This study examined laypersons' perceptions of psychotherapy, the experience of psychotherapy clients, and therapist credibility. Most of Furnham and Wardley's recent findings of positive and realistic lay views on psychotherapy and therapists were replicated. Age, sex, and psychological experience mediated some beliefs about therapy and clients' experience. Although positive views were associated with higher ratings on some aspects of therapist credibility, only the modality of the therapy (behavior vs. client-centered vs. rational-emotive individual therapy) influenced perceptions of overall credibility. Neither the fee charged nor the participant's sex had any effect on perceptions of therapist credibility. PMID- 7983214 TI - The Rorschach and the assessment of impulsivity. AB - The validity of the Rorschach as an instrument to assess impulsivity was examined in a sample of 55 adolescent psychiatric inpatients. The Rorschach variables considered to be related to impulsivity (D, Adjusted D, M, Afr, X + %, FC:CF+C, and L) were used to predict performance on the Gordon Diagnostic System (GDS). Only the discriminant function for the GDS Delay Task (which assesses the ability to formulate response strategies and to benefit from feedback) was statistically significant, with a 76.36% correct classification of subjects. The Rorschach variables with the highest correlations within the discriminant function were D, FC:CF+C, and M. The results of this study appeared to provide some support for the utility of the Rorschach in the assessment of impulsivity. PMID- 7983215 TI - Outcome predictors in a longitudinal study of high-risk boys. AB - This study of "high risk" investigated a 3-year follow-up sample of boys in the University of Rochester Child and Family Study of intact families in which at least one parent had been hospitalized for a psychiatric disorder. These families and their sons were studied in order to identify predictive factors for child outcome. Best-functioning (n = 17) and worst-functioning (n = 13) groups of boys (from a total N = 94) were differentiated successfully by time 1 parent and family interaction predictors. These variables included several measures of parent deviant communication and balanced/warm family interaction, chronicity and level of parent pathology, and socioeconomic class. Parent diagnosis was not associated significantly with outcome. PMID- 7983216 TI - Undergraduates' conflictual independence, adjustment, and alcohol use: the importance of the mother-student relationship. AB - This study investigated conflictual independence from parents (defined as a relationship free of anger and resentment), adjustment, and alcohol use among college students at a midwestern technical university (N = 109). Results showed that adjustment, as measured by the Student Adaptation to College Questionnaire (1989), was associated with having achieved conflictual independence from one's parents as measured by Hoffman's (1984) Psychological Separation Inventory. Additionally, greater alcohol use was associated with having achieved less conflictual independence from parents; the most frequent and strongest relationships occurred with respect to the mother-student relationship. The results suggested that the parent-student relationship has an impact on late adolescent development and that it also may play a role in alcohol use by college students. PMID- 7983217 TI - Raising doubts about claims of malingering: implications of relationships between MCMI-II and MMPI-2 performances. AB - Test results from 90 personal injury claimants were used to explore the relationship between personality disorders (Dependent, Histrionic, Compulsive, Schizoid, Schizotypal, Paranoid, Narcissistic, Borderline, Antisocial, Avoidant, and Passive-Aggressive) as assessed by the MCMI-II and response style measured by MMPI-2 validity scales (F, K, L, F-K, O-S, Es, and FBS). With the exception of the Dependent and Narcissistic scales, all personality disorder scales were found to have a significant relationship with validity indicators in the direction of faking bad. These results suggest that the presence of characterological factors (i.e., a personality disorder), rather than malingering, contributes to exaggerated results in a forensic setting. Implications for future research are addressed. PMID- 7983218 TI - A comparison of the differential diagnostic efficiency of three personality disorder inventories. AB - This study was a comparison of the relative diagnostic efficiency of the Millon Clinical Multiaxial Inventory-II, the MMPI Personality Disorder Scales, and the Personality Disorder Questionnaire-Revised. The Structured Clinical Interview for DSM-III-R, Axis II was used as the criterion measure. The operating characteristics of all three objective instruments revealed a high rate of false positive diagnoses, but negative test results were generally valid. Each instrument was found to possess clinical utility in its ability to improve diagnostic efficiency over base rate predictions for most disorders. It is suggested that many of the psychometric limitations revealed in this study reflect the limitations of DSM-III-R, Axis II. PMID- 7983219 TI - Behavior and cognitive therapies in France: an oral history. AB - Interviews were conducted with French psychologists and psychiatrists among those responsible for the evolution of behavioral and cognitive therapies in France. Their views are combined with information gathered from the literature to trace the history of French behavioral and cognitive therapies from their 19th century clinical precursors, through the 20th century progression from Pavlovian research to current therapeutic trends. Cultural factors favorable and unfavorable to their dissemination are discussed, as are the strategies that have been adopted by the French Association of Behavior and Cognitive Therapy to enhance its public and professional image. Particular emphasis is given to the role of an institutional context dominated by psychoanalysis. PMID- 7983220 TI - Eye movement desensitization and reprocessing in posttraumatic stress disorder: a pilot study using assessment measures. AB - Spectacular claims have been made regarding the efficacy of eye movement desensitization and reprocessing (EMDR) in the treatment of posttraumatic stress disorder (PTSD), but almost entirely on the basis of patients' reports and without objective criteria. This study reports on the treatment of eight patients with a diagnosis of PTSD who received EMDR treatment over four sessions. Assessment measures included two structured interviews, three self-report inventories, and the electromyogram (EMG). Assessments were conducted pre and posttreatment, and at 3-month follow-up. Despite some residual pathology at posttreatment and follow-up, significant improvements were obtained on all measures and across all PTSD symptom clusters. Compared with other treatments of PTSD, change was achieved in far fewer sessions. PMID- 7983221 TI - Pain ameliorating effect of eye movement desensitization. AB - This study explores the efficacy of eye movement desensitization and reprocessing (EMD/R) in the management of acute pain induced by hand exposures to ice water. Thirty participants were randomly assigned to one of the following interventions: (a) eye movement desensitization and reprocessing, (b) eye movement desensitization with music (EMD/M), and (c) control. The EMD/R participants focused on negative experiences associated with exposure to ice water, generated positive self-talk, and diverted their attention away from pain by focusing on a rapidly moving light on a monitor. The EMD with music group received eye movement desensitization coupled with preferred music. Repeated measures univariate and multivariate analysis of covariance was used to analyze the data. Results indicated that both procedures alleviated participants' pain to a similar degree and significantly more than the control, P < 0.05. PMID- 7983222 TI - Anxiety and its determinants in patients undergoing magnetic resonance imaging. AB - This study assessed anxiety reactions in 40 adults outpatients undergoing MRI. Ninety-five percent of the patients completed the procedure although 37% reported moderate to severe anxiety. It is concluded that (a) anxiety in patients undergoing MRI is a multifaceted phenomenon involving fear of enclosed places (claustrophobia), pain, the unknown, as well as apprehension about what the test might reveal, and (b) the best way to avoid traumatizing the patient is to assess these variables in advance of the procedure. Methods to reduce anxiety can then be tailored to the needs of the patient. PMID- 7983223 TI - The influence of life stress, personality, and learning history on illness behavior. AB - Previous research has suggested that prior learning experiences and current reinforcement contingencies account for a substantial portion of the variance in illness behaviors. The present study examined the role of other variables (e.g., stimulus and organismic variables). Two hundred and sixty four college students completed questionnaires that included the Life Events Survey, Hassles Scale, Hypochondriasis Scale (MMPI), Illness Attitude Scale, and a Medical Problems Survey. It emerged that social learning variables accounted for significant portions of variance in symptom reporting behavior even after other demographic, current stressor, and personality variables were accounted for. The advantages of using behavioral assessment models for conceptualizing influential variables is highlighted and directions for future research discussed. PMID- 7983224 TI - A comparison of three assessment instruments for obsessive-compulsive symptoms. AB - The psychometric characteristics and relationship among the Leyton Obsessional Inventory, Maudsley Obsessional-Compulsive Inventory, and Yale-Brown Obsessive Compulsive Scale were examined in a sample of 30 obsessive-compulsive patients diagnosed using a structured interview. The majority of the subscales of the various measures were found to have good internal consistency across gender and the mean scores were similar to those reported in other studies. There were also moderate correlations between several of the measures and clinician ratings of depression. The results suggest that (1) gender differences should be further explored in future research (2) caution should be used when extrapolating the results of treatment studies that use different OCD measures, and (3) a measure of depression should always be included in OCD studies to control for the possible effects of depressed mood. PMID- 7983225 TI - Automatic cueing to reduce drooling: a long-term follow-up with two mentally handicapped persons. AB - A follow-up was carried out on two mentally handicapped persons to check whether automatic cueing remained effective for reducing their drooling. The follow-up data were collected through observation sessions which were spread over a period of 18 months. These sessions together with the posttraining sessions of the original study covered an interval of about 2 years. The results of the follow-up showed that cueing continued to be fairly effective with drooling remaining at relatively low levels. PMID- 7983226 TI - Desensitization of dietary restraint anxiety and its relationship to weight loss. AB - In this weight reduction study, 25 female university students received desensitization treatment to lessen their dietary restraint anxiety, while a control group of 24 female university students received only relaxation training. All participants were instructed to eat less, and to return monthly to be weighed during the six-month follow-up period. Weight loss data furnished qualified support for the use of desensitization of dietary restraint anxiety as part of a comprehensive treatment program for obesity. PMID- 7983227 TI - A stimulus control technique for improving the efficacy of an established toilet training program. AB - Standard toilet training regimens used with children with developmental disabilities have demonstrated effectiveness at achieving bladder and bowel continence. However, in some clinical applications in everyday practice, success has not been achieved, necessitating research into possible modifications of the current approaches. A widely used toilet training program was modified to reduce toileting accidents of a referred child. The modification involved the assessment of the discriminative stimulus for eliminating, namely, his undergarments. By removing the undergarments when an elimination became imminent, an "errorless" learning paradigm was established that allowed for more rapid and enduring acquisition of toileting skills than seen in previous training attempts. The results indicate the present procedure could expedite training for individuals who are difficult to teach appropriate toileting skills through an analysis of the controlling antecedent stimulus for accidents and subsequent manipulation of such stimuli. PMID- 7983228 TI - Treatment and extended follow-up of chronic hand mouthing. AB - This study evaluated the relative effectiveness of differential reinforcement of other behaviors (DRO), differential reinforcement of incompatible behavior (DRI), and contingent watermist (CWM) in treating chronic self-injurious hand mouthing. The participant, a man with profound mental retardation, lived in a large residential facility. Prior to treatment he had participated in ineffective nonaversive treatments and was continuously mechanically restrained by his attending physician to promote healing of his hands. Baseline data collected in daily 30-minute sessions showed a hand mouthing rate of 1.5 responses/minute. Implementing the DRO, DRI, and CWM procedures in combination resulted in an initial 85% rate reduction. Each treatment component subsequently was withdrawn and reintroduced systematically in order to evaluate its relative effective upon hand mouthing. Only CWM plus differential reinforcement (DRO and/or DRI) had a significant effect upon hand mouthing. DRO plus DRI procedures were ineffective. In an effort to promote generalization of treatment effects, subsequent manipulations evaluated the effects of therapist proximity to the participant (one foot, 21 feet, or a random distance between one and 21 feet). Hand mouthing rates were reliably lower in the one-foot condition than in the 21-feet condition. The random proximity condition produced an intermediate performance. Direct care staff have implemented the DRI and CWM procedures throughout the participant's waking hours for nearly 3 years with almost complete elimination of hand mouthing. PMID- 7983229 TI - Treatment of obsessive compulsive disorder in the elderly: a review and case example. AB - Obsessive compulsive disorder (OCD) is a prevalent form of psychopathology in the elderly, yet limited evaluation of the disorder in this age group has occurred. We review the literature and describe a case of OCD effectively treated in an 80 year-old man. Case study reports suggest that elderly persons are responsive to selective serotonin uptake inhibitors, although medication selection and dosage may need to be adjusted as a result of the medical conditions sometimes present in the elderly. Elderly persons appear able to benefit from exposure and response prevention, although behavioral intervention has not been frequently used. We describe here the first case report where exposure and response prevention procedures were successfully used and this intervention was not confounded with psychopharmacologic treatment. PMID- 7983230 TI - Renin inhibition: a new approach to cardiovascular therapy. AB - The renin-angiotensin system (RAS) functions as a primary regulator in the short term and long-term control of blood pressure. Pharmacologic inhibition of the RAS with angiotensin-converting enzyme (ACE) inhibition is effective for treating systemic hypertension and congestive heart failure. As a more specific therapy, the development of renin inhibitors has evolved through various approaches: specific renin antibodies, peptides developed from prosegments of renin precursor, oligopeptides related to pepstatin a universal inhibitor of aspartyl proteinase enzyme, and analogs of angiotensinogen (the renin substrate). Angiotensinogen analogs are promising as therapeutic agents because of high potency, metabolic stability, and good oral bioavailability. Ongoing research is directed towards the application of renin inhibition, the treatment of various cardiovascular disorders, and as a biological probe for understanding the role of the RAS in control of blood pressure and blood volume. PMID- 7983231 TI - Genetic differences in drug disposition. AB - Genetic polymorphisms of drug metabolizing enzymes are well recognized. This review presents molecular mechanisms, ontogeny and clinical implications of genetically determined intersubject variation in some of these enzymes. Included are the polymorphic enzymes N-acetyl transferase, cytochromes P4502D6 and 2C, which have been well described in humans. Information regarding other Phase I and Phase II polymorphic pathways, such as glutathione and methyl conjugation and alcohol and acetaldehyde oxidation continues to increase and are also discussed. Genetic factors effecting enzyme activity are frequently important determinants of the disposition of drugs and their efficacy and toxicity. In addition, associations between genetic differences in these enzymes and susceptibility to carcinogens and teratogens have been reported. Ultimately, the application of knowledge regarding these genetic factors of enzyme activity may guide medical therapy and minimize xenobiotic-induced disease. PMID- 7983232 TI - Lack of hepatotoxicity with naltrexone treatment. AB - Naltrexone, a specific opiate receptor antagonist, is used clinically in the treatment of heroin addiction and more recently, for the treatment of dyskinesia associated with Huntington's disease (HD). Naltrexone may act as a potential hepatotoxin, as reflected in the elevation of transaminase levels. However, one study concluded that, for a brief treatment period of 12 weeks, there is no contraindication to naltrexone treatment based solely on increased hepatic enzyme values. This study monitored liver transaminase levels, in ten HD patients receiving daily doses, between 50 mg/day and 300 mg/day, of naltrexone for periods of 10 to 36 months. Serum glutamic oxalacetic transaminase (SGOT) and serum glutamic pyruvic transaminase (SGPT) levels were obtained before treatment and at intervals of 1 to 4 months during treatment. Only one of the ten patients treated with naltrexone had increased levels of both SGOT and SGPT, whereas one other patient showed elevated levels of SGPT. These elevations, which initially appeared dose related decreased to normal limits with continued treatment. Because many of the patients were receiving other medications, a combination of drugs with naltrexone may contribute to the increased transaminase levels seen in two of the patients. In summary, chronic administration of naltrexone in doses up to 300 mg/day for periods up to 36 months does not significantly change hepatic function, as measured by SGOT and SGPT levels. PMID- 7983233 TI - Cocaine-related sudden cardiac death: a hypothesis correlating basic science and clinical observations. AB - Sudden, unexpected death due to cocaine in young otherwise healthy individuals occurs in an idiosyncratic manner and is commonly felt to be arrhythmogenic in nature, although the exact cause of death is rarely documented. In addition to indirect sympathomimetic actions, cocaine is a potent sodium channel blocking drug and, in this regard, most closely resembles agents such as flecainide. We suggest that sudden death due to cocaine is proarrhythmic in nature, occurring under similar circumstances as that due to specific antiarrhythmic drugs. PMID- 7983235 TI - Controlled study with a new sustained-release formulation of nifedipine in essential hypertensive patients. AB - The authors studied the antihypertensive effect and tolerability of a new sustained-release formulation of nifedipine 50 mg once a day, in comparison with nifedipine retard 20 mg twice a day in patients with mild or moderate primary arterial hypertension. Both treatments significantly lowered blood pressure with no difference in daily blood pressure profile. At steady state, the two drugs determined comparable plasma levels of nifedipine as measured immediately before the morning dose. After a 12-month treatment, the new formulation of nifedipine still displayed satisfactory blood pressure control in both supine and standing positions, with no change in tolerability throughout the study. In conclusion, this new sustained-release formulation of nifedipine has similar efficacy and tolerability to conventional treatment with nifedipine retard 20 mg twice a day. PMID- 7983234 TI - Acute effects of sublingual nitroglycerin on hepatic blood flow in healthy volunteers. AB - Duplex sonography was used to assess the effects on hepatic blood flow after administering 0.6 mg nitroglycerin (NTG) sublingually to ten healthy volunteers. The study was a randomized, placebo-controlled, cross-over study in which subjects were studied on three separate occasions. Each visit involved administering either placebo or NTG followed by estimation of blood flow through a particular branch of the hepatic artery, portal vein, and hepatic vein every minute for 15 minutes after NTG and placebo administration. Two hours later, subjects were crossed over to the other treatment and the same vessel branch was again examined for 15 minutes. Total blood flow increased 7% in the portal vein and 27% in the hepatic vein during NTG treatment, but did not change significantly in the hepatic artery. Vascular resistance was increased in the hepatic artery and decreased in the portal and hepatic veins after NTG. Qualitatively, flow changed dramatically in the hepatic vein after NTG with the disappearance of normal retrograde flow. The results indicate that nitroglycerin effects hepatic blood flow through the portal and hepatic veins with a decrease in vascular resistance in the portal and hepatic veins and an increase in resistance in the hepatic artery. PMID- 7983236 TI - Pharmacokinetic disposition of loracarbef in healthy young men and women at steady state. AB - The pharmacokinetic disposition of 200- and 400-mg doses of a novel carbacephem, loracarbef, was determined over a dose interval on day 8, after ingestion of drug doses twice daily for 7 days, in 20 young, healthy volunteers of both genders. Drug was analyzed in plasma, urine, saliva, vaginal secretions, and fecal filtrate. Peak plasma concentration was proportional to dose for both men (4.0 +/ 1.3 and 8.8 +/- 3.4 mg/L) and women (8.0 +/- 5.6 and 15.3 +/- 3.3 mg/L), and the observed time to peak increased from 1 to 2 hours with the increased dose. Apparent volume of distribution was greater in men than women (0.385 +/- 0.114 versus 0.270 +/- 0.075 L/kg; P < .03). The drug was virtually quantitatively excreted unchanged in urine, and its renal clearance exceeded creatinine clearance in all subjects. Renal loracarbef clearance correlated with neither weight-corrected dose nor creatinine clearance in these healthy subjects. There was no evidence for drug accumulation in the body with chronic ingestion. Loracarbef was detected in the fecal filtrate of seven volunteers, but did not account for more than 7% of the daily dose. Loracarbef was detected in vaginal secretions of two of five volunteers who ingested the 400-mg dose. No drug was detected in saliva obtained just before dose ingestion. These data are consistent with complete bioavailability for an oral beta-lactam antibiotic drug that is virtually completely eliminated unchanged by the kidney. PMID- 7983237 TI - Pharmacokinetics and safety of NM441, a new quinolone, in healthy male volunteers. AB - The safety and pharmacokinetics of NM441, a prodrug of a new thiazeto-quinoline carboxylic acid derivative, NM394, were evaluated in healthy male volunteers given the drug orally in single doses of 20, 50, 100, 200, and 400 mg, and multiple doses of 300 mg twice daily for 6.5 days. No remarkable abnormalities were observed in symptoms, physical tests, laboratory tests, electrocardiogram (ECG), electroencephalogram (EEG), or equilibrium test. The mean plasma concentrations of active metabolite NM394 peaked between 0.5 and 1.0 hours, and the maximum concentrations were 0.68, 1.09, and 1.88 micrograms/mL at doses of 100, 200, and 400 mg, respectively. The mean half-lives were 7.7 to 8.9 hours and were not affected by dose. The mean urinary excretion rates of NM394 were 46.0, 38.3, and 30.6% of the doses within 48 hours, respectively, and other metabolites were excreted in urine by 7% of the doses. The mean salivary concentrations of NM394 were approximately 20% of the plasma concentrations. The mean fecal excretion rates of NM394 and NM441 were 52.9 and 4.2%, respectively within 72 hours after dosing of 400 mg. The Cmax, AUC, and urinary excretion rates were not altered by food intake, whereas the Tmax was prolonged slightly. In the multiple dose study, the steady state of plasma concentration of NM394 was achieved on day 3 or 4, and further accumulation did not occur thereafter. The mean urinary excretion rate of NM394 was 49.0% during and 48 hours after the multiple administration. The acceptable safety and tolerance and defined pharmacokinetic characteristics of NM441 support further testing. PMID- 7983238 TI - Human pharmacokinetic study of immediate-release (codeine phosphate) and sustained-release (codeine Contin) codeine. AB - The authors compared, in a double-blind, randomized, crossover study in 13 healthy adult volunteers, the single- and multiple-dose pharmacokinetics, relative bioavailability, and side effects of a new oral sustained-release formulation of codeine (SRC) containing 150 mg codeine base, with oral immediate release codeine phosphate (IRC). Sustained-release codeine was given at a dose of 150 mg every 12 hours for 5 doses; IRC was given at a dose of 60 mg (2 x 30 mg) every 4 hours for the first 3 doses, and 30 mg every 4 hours thereafter for 12 doses. Plasma codeine levels were determined using a sensitive and specific high performance liquid chromatography method and corrected for dose administered and codeine base equivalent. Mean values for single-dose pharmacokinetic parameters for SRC and IRC, respectively, were: Cmax of 217.8 and 138.8 ng/mL; Tmax of 2.3 and 1.1 hours; AUC0-inf of 1202.3 and 1262.4 ng.mL-1.hour-1; and t1/2el of 2.6 hours for both formulations. Their respective mean steady-state pharmacokinetic parameters were: Cmax of 263.8 and 222.9 ng/mL; Tmax of 3.2 and 1.1 hours; AUC0 12h of 1576.4 and 1379.1 ng.mL-1.hour-1; and t1/2el of 2.8 and 2.3 hours. These results indicate comparable bioavailability between both formulations with SRC providing delayed peak plasma levels. The sustained-release character of SRC can be explained by a delayed absorption, which is not limiting to drug elimination. Sustained-release codeine provides higher plasma codeine levels over a broader time interval and is expected to improve pain management. PMID- 7983239 TI - Critical comparison of novel and existing methods of compliance assessment during a clinical trial of an oral iron chelator. AB - The assessment of compliance is critical in the evaluation of the effectiveness of a new therapeutic agent. Fifteen patients with transfusion-dependent beta thalassemia, many of whom had previously demonstrated erratic compliance with deferoxamine, were enrolled in a clinical trial of a new oral iron chelator, 1,2 dimethyl-3-hydroxypyrid-4-one (L1). Their compliance with this medication was estimated by several existing methods and the novel Medication Event Monitoring System (MEMS). Overall compliance as assessed by the MEMS was 78.5 +/- 13.0% of prescribed doses taken, significantly lower than the corresponding rates calculated by pill counts and diaries (91.5 +/- 9.2% and 94.1 +/- 4.3%, respectively). However, several serious problems were encountered with the MEMS, mostly in the form of incorrect use of the device by the patients. Disclosure of the nature of the MEMS and the compliance monitoring process did not alter the rate of adherence with L1 therapy. Compliance as determined by pill counts did not differ between the 1st and 2nd 6-month periods. Although not reaching statistical significance, a trend towards better L1 compliance occurred in those patients in whom serum ferritin levels decreased. Patients who filled at least 50% of their diaries had significantly better compliance by pill counts than those who completed less than 50% of their diaries (95.9 +/- 4.1% and 86.5 +/- 11.1%, respectively). Steady-state L1 trough concentrations and 24-hour urinary iron excretion did not correlate with L1 compliance.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7983240 TI - Neuropeptide Y immunoreactivity identifies a regularly arrayed group of amacrine cells within the cat retina. AB - Retinal amacrine cells can be divided into subgroups on the basis of morphological properties and chemical content. It is likely that these subgroups have specific connections and serve unique functional roles within the inner plexiform layer. In the present study we show that immunoreactivity to neuropeptide Y (NPY) identifies a group of amacrine cells (165,000-170,000) within the adult cat retina. This is the largest group of peptide-containing amacrine cells identified to date in the cat retina. These neurons have small cell bodies and are regularly spaced at all retinal eccentricities examined. The density of NPY-immunoreactive cells, as well as their regular spacing, suggests that these neurons form a specific subgroup of the amacrine cell class and are likely to serve a unique role in the transfer of visual information through the inner plexiform layer. PMID- 7983241 TI - Effects of vagal afferent nerve stimulation on noxious heat-evoked Fos-like immunoreactivity in the rat lumbar spinal cord. AB - Electrophysiological and behavioral studies have described modulation of nociception by vagal afferent fibers. The objectives of this study were to 1) use Fos-like immunoreactivity as a marker for neuronal activity to examine populations of neurons in the spinal cord that are activated by a noxious heat stimulus, 2) determine whether heat-evoked Fos-like immunoreactivity can be modulated by vagal afferent stimulation, and 3) determine whether vagally mediated effect on heat-evoked Fos-like immunoreactivity can be blocked by intrathecally administered serotoninergic receptor and alpha-adrenergic receptor antagonists. Neurons demonstrating Fos-like immunoreactivity were located in the ipsilateral superficial and deep dorsal horn laminae extending from the caudal L3 through the rostral L6 region of the spinal cord. Stimulation of the right cervical vagus nerve attenuated significantly (42%) heat-evoked Fos-like immunoreactivity in the superficial laminae. The reduction in Fos-like immunoreactivity by vagal stimulation was abolished by intrathecal administration of methysergide, a nonselective serotoninergic receptor antagonist, but not by phentolamine, a nonselective alpha-adrenoceptor antagonist. These results suggest that vagal afferent modulation of spinal nociceptive transmission is mediated, at least in part, by serotonin receptors. PMID- 7983242 TI - Development of calretinin immunoreactivity in the mouse inner ear. AB - Calretinin is a calcium-binding protein of the EF-hand family. It has been previously identified in particular cell types of adult guinea pig, rat, and chinchilla inner ear. Development of calretinin immunoreactivity in the mouse inner ear was investigated from embryonic day 13 (E13) to the adult stage. In the adult mouse vestibule, calretinin immunoreactivity was present in the same structures as described for the rat and guinea pig: the population of afferent fibers forming calyx units and a small number of ganglion neurons. The earliest immunoreactivity was found at E17 in vestibular hair cells (VHCs), then, at E19, in afferent fibers entering the sensory epithelia and in rare ganglion neurons. At postnatal day 4 (P4), a few vestibular nerve fibers and ganglion neurons were reactive. From this stage until P14, immunoreactivity developed in the calyx units and disappeared from VHCs. At P14, immunostaining was adult-like. In the adult mouse cochlea, immunoreactivity was present in the same cell populations as described in the rat: the inner hair cells (IHCs) and most of Corti's ganglion neurons. Calretinin immunoreactivity appeared at E19-P0 in IHCs and ganglion neurons of the basal turn. At P1, outer hair cells (OHCs) of the basal turn were positive. Calretinin immunoreactivity then appeared in IHCs, OHCs, and ganglion neurons of the medial turn, then of the apical turn. At P4, all IHCs and OHCs and most of the ganglion neurons were immunostained. Immunoreactivity gradually disappeared from the OHCs starting at P10 and, at P22, only IHCs and ganglion neurons were positive. The sequences of appearance of calretinin were specific to each cell type of the inner ear and paralleled their respective maturation. Calretinin was transiently expressed in VHCs and OHCs. PMID- 7983243 TI - Intrabulbar associational system in the rat olfactory bulb comprises cholecystokinin-containing tufted cells that synapse onto the dendrites of GABAergic granule cells. AB - The intrabulbar associational system (IAS) originates from tufted cells whose axons terminate in the internal plexiform layer (IPL) on the opposite side of the same olfactory bulb. The postsynaptic targets of the IAS are unknown. Subpopulations of tufted cells contain different neuropeptides and transmitters but it is not known if tufted cells forming the IAS are homogeneous with respect to neurotransmitters. Therefore, the goals of the present study were to identify the postsynaptic targets of the IAS and to determine the major transmitter in this intrabulbar circuit. Biocytin anterograde tracing revealed that the axons of superficially situated tufted cells coursed directly to the IPL where they turned abruptly to run ventrally and dorsally to terminate in the IPL on the opposite side of the olfactory bulb. WGAapoHRP-Au retrograde tracing combined with immunohistochemistry for CCK revealed that all tufted cells retrogradely labeled by WGAapoHRP-Au injection in the IPL were immunoreactive for CCK. Anterograde transport of biocytin combined with postembedding immunocytochemical gold labeling for GABA demonstrated that labeled IAS axons terminate predominantly, if not exclusively, on GABAergic granule cell dendrites in the IPL. These results confirm that the IAS arises from tufted cells and is topographically organized. We further demonstrate that tufted cells forming the IAS use the neuropeptide CCK as a transmitter. In addition, we show that the postsynaptic targets of the CCKergic IAS are the dendrites of GABAergic granule cells coursing through the IPL toward the EPL. As CCK is generally an excitatory neuropeptide, we suggest that the IAS functions to excite topographically discrete populations of granule cells. This action may lead to inhibition of equally discrete populations of mitral/tufted cells. Thus, the IAS may be an intrabulbar inhibitory circuit that coordinates topographically organized neural networks in the olfactory bulb. PMID- 7983245 TI - Development of the retinofugal projections in the embryonic and larval zebrafish (Brachydanio rerio). AB - Studies of the projection from the vertebrate retina have contributed significantly to current concepts of neural development. The zebrafish has recently become a favored system for the study of development in general and neural development in particular. Although the development of both the optic nerve and the retinotectal projection of the zebrafish has been described, the retinofugal projection in its entirety has not. This paper describes it and also addresses the issue of projectional exuberance: i.e., transient projections to targets that are not innervated in the adult. The retinofugal projection of embryonic and larval zebrafish (32 hours to 7 days post-fertilization) was labeled by intraocular injection of DiI (1,1'-dioctadecyl 3,3,3',3',tetramethylindocarbocyanine perchlorate) and then studied in wholemounts and sections. The first optic axons crossed the chiasm at 32 hours post-fertilization and projected in a straight line to reach the tectum at about 44 hours. At 48 hours, a few optic axons deviated along either the tract of the posterior commissure or the tract of the postoptic commissure. By 72 hours (about the time of hatching) optic axons arborized in ten distinct regions, termed arborization fields. At 6-7 days post-fertilization, the same ten arborization fields (nine contralateral, one bilateral) were evident. Most of the arborization fields were located in the superficial neuropil and were not associated with morphologically identifiable clusters of somata. On the basis of various landmarks, the ten arborization fields are identified as precursors of retinorecipient nuclei previously described in other adult cypriniform fishes. The development was characterized by the nearly complete absence of any transient projections. Thus, the idea that axonal outgrowth is initially exuberant and trimmed back later is not supported by these results. PMID- 7983244 TI - Early embryonic expression of a 60-kD glycoprotein in the developing nervous system of the lobster. AB - To investigate the developmental processes that generate the crustacean nervous system, we used a monoclonal antibody that recognises an antigen that is expressed in the developing embryonic nervous system of the lobster, Homarus gammarus. Expression of this antigen commences early in embryogenesis, occurs in all parts of the embryonic central and peripheral nervous systems, and continues into adulthood. Initial expression in the central nervous system correlates with the onset of neuronal process outgrowth. Light microscopic analysis shows that the antigen is found surrounding the cell bodies and processes of all neurons. Biochemical analysis indicates that the antigen is a glycoprotein with an apparent molecular weight of 60 kD. Due to the early embryonic onset of its expression, this antigen is a useful cellular label for visualisation of pattern formation in the developing nervous system; this is documented in detail for the developing stomatogastric nervous system. The fact that the 60-kD antigen is expressed early in embryogenesis throughout the nervous system suggests that it might play an important role in the development of the lobster nervous system. PMID- 7983246 TI - Electrophysiological and morphological properties of light and dark cells isolated from mudpuppy taste buds. AB - Isolated Necturus taste receptor cells were studied by giga-seal whole-cell recording and electron microscopy to correlate electrophysiological properties with taste cell structural features. Dark (type I) cells were identified by the presence of dense granular packets in the supranuclear and apical regions of the cytoplasm. In response to a series of depolarizing voltage commands from a holding potential of -80 mV, these cells exhibited a transient, TTX-sensitive inward Na+ current, a sustained outward K+ current, and a slowly inactivating inward Ca++ current. Light (type II) cells were identified by a lack of granular packets and by an abundance of smooth endoplasmic reticulum distributed throughout the cell. In addition, isolated light cells had clear vesicular inclusions in the cytoplasm and blebs on the plasma membrane. Light cells were divided into two functional populations based upon electrophysiological criteria: cells with inward and outward currents, and cells with outward currents only. Light cells with inward and outward currents had voltage-activated Na+, K+, and Ca++ currents with properties similar to those of dark cells. In contrast, the second group of light cells had only voltage-activated outward K+ currents in response to depolarizing voltage commands. These data suggest that dark cells and light cells with inward and outward currents are capable of generating action potentials and releasing neurotransmitters onto gustatory afferent neurons in response to taste stimulation. In contrast, light cells with outward currents only likely serve a different function in the taste bud. PMID- 7983247 TI - Innervation of footpads of normal and mutant mice lacking sweat glands. AB - Footpads of normal adult mice are innervated by sympathetic and sensory fibers. The sympathetic fibers associated with sweat glands contain acetylcholinesterase and immunoreactivity for vasoactive intestinal peptide. Although catecholamine histofluorescence is absent, the gland innervation exhibits immunoreactivity for tyrosine hydroxylase. A distinct population of sympathetic fibers, which possess catecholamines and neuropeptide Y as well as tyrosinehydroxylase immunoreactivity, innervates blood vessels. Sensory fibers containing immunoreactivity for substance P and calcitonin gene-related peptide course beneath the epidermis and some form endings in it. Treatment of neonatal mice with the adrenergic neurotoxin, 6-hydroxydopamine, results in loss of sympathetic innervation of sweat glands and blood vessels, permits growth of sensory axons into sweat glands, but does not alter the peptidergic sensory innervation of the dermis and epidermis. Three mouse mutations, Tabby (Ta), crinkled (cr), and downless (dl), disrupt the interactions between the mesenchyme and epidermis that are required for normal development of specific epidermal derivatives, including sweat glands. The sympathetic innervation of blood vessels and sensory innervation of footpad skin of the three mutant mice that lack sweat glands is indistinguishable from normal. The sympathetic fibers that normally innervate sweat glands, however, are not present. These results indicate that in the absence of their normal target, the sympathetic fibers that innervate sweat glands are lacking. Furthermore, they suggest that, although sensory fibers may sprout into sympathetic targets in the footpad, the domains occupied by sensory fibers are not normally accessible to sympathetic axons. PMID- 7983248 TI - The composition and function of the pulmonary surfactant system during metamorphosis in the tiger salamander Ambystoma tigrinum. AB - Mammalian lungs secrete a mixture of surface-active lipids (surfactant), which greatly reduces the surface tension of the fluid coating the inner lung surface, thereby reducing the risk of collapse upon deflation and increasing compliance upon inflation. During foetal lung maturation, these lipids become enriched in the primary and active ingredient, a disaturated phospholipid. However, disaturated phospholipids exist in their inactive gel-like form at temperatures below 37 degrees C and thus are inappropriate for controlling surface tension in the lungs of many ectotherms. We examined the development of the composition and function of the surfactant system of the tiger salamander (Ambystoma tigrinum) during metamorphosis from the fully aquatic larva (termed stage I) through an intermediate air-breathing larval form (stage IV) to the terrestrial adult (stage VII). Biochemical analysis of lung washings from these three life stages revealed a decrease in the percentage of disaturated phospholipid per total phospholipid (23.03 versus 15.92%) with lung maturity. The relative cholesterol content remained constant. The increased level of phospholipid saturation in the fully aquatic larvae may reflect their generally higher body temperature and the higher external hydrostatic compression forces exerted on the lungs, compared to the terrestrial adults. Opening pressure (pressure required for initial lung opening) prior to lavage decreased from larval to adult salamanders (7.96 versus 4.69 cm H2O), indicating a decrease in resistance to opening with lung development.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7983249 TI - 5-Hydroxytryptamine2 and 5-hydroxytryptamine3 receptors mediate serotonin-induced short-circuit current in pig jejunum. AB - The purpose of this study was to determine the effect of methysergide, ketanserin, granisetron, cisapride, and renzapride on serotonin (5 hydroxytryptamine-evoked short-circuit current in muscle and myenteric plexus stripped pig jejunum using the Ussing chamber technique. Ketanserin, granisetron, cisapride, and renzapride all reduced the 5-hydroxytryptamine-induced increase in short-circuit current by about 50%. Combination of ketanserin and granisetron only reduced the 5-hydroxytryptamine-induced peak increase in short-circuit current by 25%. Cisapride caused a small concentration-dependent increase in short-circuit current. Atropine and hexamethonium both almost completely suppressed the cisapride-induced peak increase in short-circuit current. Atropine and hexamethonium both almost completely suppressed the cisapride-induced peak increase in short-circuit current. Ketanserin, granisetron, methysergide, and renzapride did not alter the basal short-circuit current. These results suggest that 5-hydroxytryptamine elicits an increase in short-circuit current by activating epithelial and submucosal 5-hydroxytryptamine2 and 5 hydroxytryptamine3 receptor subtypes. Furthermore, the short-circuit current increasing effect of cisapride, is due to activation of at least muscarinic and nicotinic receptors. PMID- 7983250 TI - Liver metabolism in cold hypoxia: a comparison of energy metabolism and glycolysis in cold-sensitive and cold-resistant mammals. AB - The effects of cold hypoxia were examined during a time-course at 2 degrees C on levels of glycolytic metabolites: glycogen, glucose, glucose-1-phosphate, glucose 6-phosphate, fructose-6-phosphate, fructose-1,6-bisphosphate, phosphoenolpyruvate, pyruvate, lactate and energetics (ATP, ADP, AMP) of livers from rats and columbian ground squirrels. Responses of adenylate pools reflected the energy imbalance created during cold hypoxia in both rat and ground squirrel liver within minutes of organ isolation. In rat, ATP levels and energy charge values for freshly isolated livers were 2.54 mumol.g-1 and 0.70, respectively. Within 5 min of cold hypoxia, ATP levels had dropped well below control values and by 8 h storage, ATP, AMP, and energy charge values were 0.21 mumol.g-1, 2.01 mumol.g-1, and 0.17, respectively. In columbian ground squirrels the patterns of rapid ATP depletion and AMP accumulation were similar to those found in rat. In rat liver, enzymatic regulatory control of glycolysis appeared to be extremely sensitive to the decline in cellular energy levels. After 8 h cold hypoxia levels of fructose-6-phosphate decreased and fructose-1,6-bisphosphate increased, thus reflecting an activation of glycolysis at the regulatory step catalysed by phosphofructokinase fructose-1,6-bisphosphatase. Despite an initial increase in flux through glycolysis over the first 2 min (lactate levels increased 3.7 mumol.g-1), further flux through the pathway was not permitted even though glycolysis was activated at the phosphofructokinase/fructose-1,6-bisphosphatase locus at 8 h, since supplies of phosphorylated substrate glucose-1-phosphate or glucose-6-phosphate remained low throughout the duration of the 24-h period.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7983252 TI - The Cochrane Collaboration: oral health group. PMID- 7983251 TI - Anoxia induces changes in translatable mRNA populations in turtle organs: a possible adaptive strategy for anaerobiosis. AB - The effects of anoxic submergence (16 h at 15 degrees C) on cellular mRNA contents were assessed in five organs of anoxia tolerant turtles Trachemys scripta elegans. Poly(A)+ RNA was extracted from liver, red and white skeletal muscle, kidney and heart of control and anoxic turtles, as well as from heart and kidney of turtles allowed 24 h aerobic recovery (at 15 degrees C) after anoxia exposure. Poly(A)+ RNA content increased by 30% in white muscle from anoxic turtles relative to control animals but was unchanged by metabolic state in other organs. Extracted mRNA was translated in vitro in a wheat germ lysate system and the 35S-labelled polypeptides that were produced were separated by sodium dodecyl sulphate-polyacrylamide gel electrophoresis. Overall translational activity of the mRNA pool [cpm 35S-methionine incorporated per microgram poly(A)+ RNA] was altered by anoxia exposure in three organs, increasing by 38 and 18% in liver and kidney and decreasing by 42% in red muscle. Anoxia exposure also led to qualitative changes in the protein products that resulted from in vitro translation. Sodium dodecyl sulphate polyacrylamide gel electrophoresis revealed the presence of a novel 19.5-kDa polypeptide in liver of anoxia-exposed animals as well as increased amounts of two other proteins at 28.6 and 79.9 kDa. In heart a new translation product of 26.8 kDa appeared in anoxia, and in kidney a 32.8 kDa polypeptide was produced during the aerobic recovery period after anoxia exposure. Anoxia stimulated the appearance of a 37.5-kDa protein in red skeletal muscle but anoxic red muscle also lost proteins of 40, 32, and 28.2 kDa that were present in aerobic controls. Anoxia exposure did not change the proteins produced by in vitro translation in white muscle. The results suggest that anoxia exposure triggers rapid cellular responses in T. s. elegans that modify translatable mRNA populations in organs, leading to new protein transcripts.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 7983253 TI - Chewing performance before and after rehabilitation of post-canine teeth in man. AB - Missing teeth are often replaced by fixed or removable prosthodontic appliances to improve masticatory function. However, there have been few studies directly determining the influence of prosthodontic treatment on masticatory function. Our aim was to obtain information on the objective and subjective masticatory function of partially edentulous subjects before and after prosthetic restoration. In this way, the improvement of the masticatory function as a result of the treatment could be quantified. The objective and subjective masticatory function of a group of 15 subjects was determined before and after replacement of an average of 3.1 post-canine teeth. The results were compared with data from a control group of 26 subjects having a complete dentition. The total number of occluding post-canine teeth increased as a result of the prosthodontic treatment, yielding a significantly improved objective masticatory function. The average masticatory performance was found to approach the level of the control group if all occlusal units of the longest posterior side were replaced. Subjects with an incomplete dentition tended to chew predominantly on the side of the longest posterior arch. The average subjective masticatory function improved as a result of the treatment. The appreciation of the masticatory function after treatment was equal to that of the control group, despite an average of 2.7 missing teeth. However, no correlation was found between the additional number of occlusal units and the change in subjective masticatory performance. Rehabilitation of post canine teeth restores some objective masticatory function and leads to an increased appreciation of the masticatory function, although no correlation was found between the changes in objective and subjective masticatory function. PMID- 7983254 TI - An investigation into the pressure transmitted to the pulp chamber on crown cementation: a laboratory study. AB - Pressure changes in the pulp chamber resulting from crown cementation have not been previously quantified. An experiment was designed to investigate the effect of smear layer removal on the peak pressure transmitted to the pulp chamber with crown cementation. Ten matched pairs of single-rooted premolar teeth were collected from adolescents and prepared for full-coverage crowns. The pulp tissue from each tooth was removed. One tooth from each pair had the smear layer removed with the application of 37% phosphoric acid for 30 s. The null hypothesis states that the removal of the dentinal smear layer will not change pressure in the pulp chamber resulting from the cementation. Before cementation, a hydrostatic head of pressure was used to perfuse the tooth, and the perfusion rate was recorded. Crowns were cemented with zinc phosphate cement with a seating force of 100 N. The mean peak pressures recorded were 85 Pa (SE 12 Pa) with the smear layer intact, and 194 Pa (SE 49 Pa) when the dentin was etched. The difference in the peak pressures transmitted to the pulp chamber with the two groups was significant (p < or = 0.05). A significant negative correlation was found between dentin thickness and the peak pressure transmitted to the pulp chamber (r = 0.5531, p < or = 0.01). We have shown that the pressure transmission to the pulp chamber during crown cementation can be measured. Since smear layer removal significantly influences the peak pressure, it is concluded that the pressure detected is at least partially dependent on the fluid flow through the dentin. PMID- 7983255 TI - Clinical status of ten dentin adhesive systems. AB - Laboratory testing of dentin adhesive systems still requires corroboration by long-term clinical trials for their ultimate clinical effectiveness to be validated. The objective of this clinical investigation was to evaluate, retrospectively, the clinical effectiveness of earlier-investigated dentin adhesive systems (Scotchbond, Gluma, Clearfil New Bond, Scotchbond 2, Tenure, and Tripton), and to compare their clinical results with those obtained with four modern total-etch adhesive systems (Bayer exp. 1 and 2, Clearfil Liner Bond System, and Scotchbond Multi-Purpose). In total, 1177 Class V cervical lesions in the teeth of 346 patients were restored following two cavity designs: In Group A, enamel was neither beveled nor intentionally etched, as per ADA guidelines; in Group B, adjacent enamel was beveled and conditioned. Clinical retention rates definitely indicated the improved clinical efficacy of the newest dentin adhesives over the earlier systems. With regard to adhesion strategy, adhesive systems that removed the smear layer and concurrently demineralized the dentin surface layer performed clinically better than systems that modified the disorderly layer of smear debris without complete removal. Hybridization by resin interdiffusion into the exposed dentinal collagen layer, combined with attachment of resin tags into the opened dentin tubules, appeared to be essential for reliable dentin bonding but might be insufficient by itself. The additional formation of an elastic bonding area as a polymerization shrinkage absorber and the use of a microfine restorative composite apparently guaranteed an efficient clinical result. The perfect one-year retention recorded for Clearfil Liner Bond System and Scotchbond Multi-Purpose must be confirmed at later recalls. PMID- 7983256 TI - Orientational micro-Raman spectroscopy on hydroxyapatite single crystals and human enamel crystallites. AB - Single crystals of synthetic hydroxyapatite have been examined by orientational micro-Raman spectroscopy. The observed Raman bands include the PO4(3-)/OH internal and external modes over the spectral range from 180 to 3600 cm-1. The Raman-active symmetry tensors (A, E1, and E2) of crystal-class C6 have been assigned to these bands. Intensities of the Raman bands are invariant to the orientation of the a- or b-axis of a single crystal, but depend solely on the c axis orientation. Changes in the spectral profile thus reflect changes in the c axis orientation, which, with respect to the known excitation/observation coordinates, can be determined through the angular dependencies of Raman bands due to A and E2 symmetries. The useful bands are those of the PO4(3-)v4 vibrational mode, which contains relatively well-defined bands due to E2 (581 cm 1) and A (593 cm-1) symmetries. A preliminary Raman study on crystallites near the intact outer surface of human enamel has also been carried out. Strong orientational dependencies similar to those of hydroxyapatite single crystals have been observed among the bands in enamel spectra. This suggests that the crystallites in the region investigated are highly oriented. The results were consistent with an averaged orientation of the crystallite c-axis being perpendicular to the outer surface. PMID- 7983257 TI - Reduced mercury vapor release from dental amalgams prepared with binary Hg-in liquid alloys. AB - For the past ten years, the amounts of mercury vapor released from dental amalgams and the possibility of side-effects caused by these amounts have been discussed. Although no adverse health effects have been substantiated from these minute amounts, besides rare cases of allergies, this release should be reduced. The aim of this study was to reduce the mercury evaporation from a high-copper amalgam during setting by triturating the alloy powder with binary Hg-In liquid alloys having various indium concentrations set at 0, 5, 10, 20, 30, 40, and 50 wt%. Specimens (n = 4) were made for each amalgam according to ANSI/ADA Specification #1 and placed into a measuring chamber kept at 36.5 +/- 0.5 degrees C, through which a continuous air flow of 0.75 L/min was pumped. The total mercury release was measured during the setting period, according to the method described by Ferracane et al. (1992). Four additional specimens were prepared from a modified 14% Indisperse amalgam powder for the purpose of comparison. The results showed that the release of mercury vapor decreased with increasing indium concentrations, and that the amalgams made with the Hg-In liquid alloy with 10% In or more released significantly less mercury than the modified 14% Indisperse. The method of mixing indium in mercury prior to trituration appeared to be another effective method for reducing mercury evaporation during setting. The reduced mercury release may be explained by a reduction of mercury concentration in the structure, a reduction of vapor pressure for the mercury in the matrix phases, or more efficient formation of a surface oxide layer. PMID- 7983258 TI - Human salivary acidic proline-rich protein polymorphisms and biosynthesis studied by high-performance liquid chromatography. AB - Human salivary acidic proline-rich proteins (PRPs) constitute a significant fraction of the total salivary protein and possess important biological activities. Different genetic and post-translationally processed forms of the PRPs exhibit significant quantitative variations in several of these activities, especially the modulation of salivary calcium phosphate chemistry and oral bacterial adhesion. To quantify and understand these differences, we have developed a high-performance liquid chromatography (HPLC) method to identify and measure individual PRPs in saliva. The data obtained permit the identification of PRP polymorphisms and phenotypes, the determination of the relative amounts of PRPs derived from the two loci, PRH1 and PRH2, and the measurement of the extent of post-translational cleavage of the primary polypeptide products. Substantial inter-gland and inter-individual variations were found in relative amounts of PRPs derived from the two loci (at least two-fold), and in post-translational cleavage (greater than two-fold), both of which are likely to be biologically significant. Also in this study, the presence of what appear to be minor amounts of numerous variant PRPs in glandular secretions was observed, and two uncommon PRP polymorphisms were identified in the 127 subjects studied. PMID- 7983259 TI - The predominant cultivable flora of sound and carious human root surfaces. AB - Little detailed knowledge exists about the composition of the human root flora. Therefore, the predominant cultivable flora (PCF) was determined for samples of: (1) plaque from sound root surfaces (SRS) in eight subjects without root caries, (2) plaque from incipient root lesions (IRL) in eight subjects with root caries, and (3) carious material from advanced root lesions (ARL) in nine other subjects with root caries. Generally, one root surface was sampled per subject, and organisms-358, 512, and 389 for SRS, IRL, and ARL, respectively-were identified by standard methods. It was found that: (1) streptococci, actinomyces, and veillonellae constituted 84.2, 57.8, and 65.7% of the PCF of SRS, IRL, and ARL samples, respectively; (2) a wide variety of other Gram-positive cocci and Gram positive and -negative rods was also present; (3) the PCF of many samples was often dominated by few organisms, the identity of which differed from sample to sample; (4) a negative and no association with root caries existed for the PCF levels of the non-mutans streptococci (non-MS) and the actinomyces; and (5) mutans streptococci (MS) and lactobacilli (L) were not always present among the PCF of IRL and ARL, respectively, and non-MS were isolated from the PCF of most lesions and actinomyces from all lesions. Our findings illustrate the complexity of the root surface flora and suggest that root caries development involves organisms other than MS and L. PMID- 7983260 TI - Maxillary molar extraction decreases stiffness of the mandible in ovariectomized rats. AB - Although osteoporosis is a major public health concern, the effect of this condition on oral bone has not been determined. Using the ovariectomized rat as a model, we examined whether acute estrogen depletion affects the mandible of the ovariectomized rat with and without maxillary molar extraction. Twenty-two ovariectomized and 20 sham-ovariectomized 90-day-old Sprague-Dawley rats were divided into the following groups: (1) sham-ovariectomized, baseline control; (2) ovariectomized, baseline control; (3) ovariectomized; (4) ovariectomized, tooth extraction; (5) sham-ovariectomized; and (6) sham-ovariectomized, tooth extraction. On day eight, sham-ovariectomized and ovariectomized rats had all their maxillary molars extracted, and the baseline control sham-ovariectomized and ovariectomized rats were killed. On day 35, the remaining animals were killed. After teeth were harvested, the right mandible was tested to failure in three-point bending. The bone mineral density of the left mandible was measured with dual-energy x-ray absorptiometry. The area fraction and area moment of inertia of a section of mandible were determined. Neither ovariectomy nor tooth extraction significantly affected the bone mineral density or structural properties of the rat mandible. However, there was an interaction between ovariectomy and maxillary molar extraction on the stiffness of the rat mandible (p < 0.008). Maxillary molar extraction decreased the stiffness of the mandible by 25% (p < 0.05) in the ovariectomized rat, whereas it did not do so in the sham ovariectomized rat. PMID- 7983261 TI - A quantitative study of calcium binding by isolated streptococcal cell walls and lipoteichoic acid: comparison with whole cells. AB - Calcium-binding by surface components of oral bacteria may have important effects on remineralization/demineralization phenomena and plaque cohesion. Additionally, some species export large quantities of lipoteichoic acid, possibly as a protective measure. Measurement of calcium-binding can facilitate prediction of how this will effectively buffer plaque fluid calcium concentration and affect these processes. Using equilibrium dialysis, we measured calcium-binding capacities and affinities at pH 7.0 in isolated cell walls of Streptococcus downei, S. sanguis, and purified lipoteichoic acid (LTA) of S. sanguis. Mean binding capacities were: 56.5 mumol Ca/g wet weight for S. downei cell walls and 47.2 mumol Ca/g wet weight for S. sanguis cell walls, and 1.11 mol Ca/mol LTA phosphate were found. Mean dissociation constants (mmol/L) for cell wall calcium binding were 2.16 mmol/L (S. downei) and 2.69 mmol/L (S. sanguis). These constants were not significantly different from those for whole cells of the same species (Rose et al., 1993), but the dissociation constant for LTA (7.82 mmol/L) was significantly higher and suggested a different mode of binding. At neutral pH, at the known calcium concentration of plaque fluid, whole cells and cell walls are likely to be completely saturated with calcium, whereas free LTA is only 30% saturated. The large amounts of LTA exported by some sucrose-grown streptococci may therefore act as a calcium buffer and so protect the organisms against high local concentrations of calcium produced during demineralization. PMID- 7983262 TI - Chemostat flow cell system: an in vitro model for the evaluation of antiplaque agents. AB - We developed an experimental in vitro model of dental plaque to assess the potential efficacy of antiplaque agents. The model used a chemostat, which provided a continuous source of 5 species of oral bacteria grown in an artificial "saliva-like" medium. This mixture was pumped through six flow cells, each containing two types of surfaces on which plaque formed and was subsequently measured. Formation of bacterial plaque on hydroxyapatite surfaces was assessed by measurement of the DNA and protein content of the plaque film. The amount of bacterial plaque formed on germanium surfaces was measured by attenuated total reflectance (ATR/FT-IR) spectroscopy. Plaque viability was also assessed by a fluorescent staining technique. The quantity of plaque formed on both types of surfaces gradually increased with the duration of flow (from 24 to 72 h) through the cells during a 72-hour experimental period. The flow cells were then pulsed with experimental treatment solutions for 30 s, twice daily. Parallel to results of human clinical studies, the model was capable of discriminating among water, a placebo mouthrinse, and an active antimicrobial mouthrinse formulation containing 0.03% triclosan. It therefore offers a valuable alternative to animal model testing and allows for more rapid evaluations under well-controlled experimental conditions. PMID- 7983263 TI - Ethics in research: current issues for dental researchers and their professional society. AB - Values associated with scientific investigations affect the conduct, evaluation, and reporting of research and lead to ethical issues for scientists engaged in dental research. This essay examines the relationship between scientists and the larger society in which they work, and how that relationship defines the boundaries of scientific freedom and autonomy, on the one hand, and scientific responsibility and accountability, on the other. Values underlie disputes over data sharing, perceptions of conflict of interest, and scientists' commitment to research integrity. Professional societies, such as the IADR, can be a major influence in shaping the moral tone and ethical climate for research through the adoption of standards, the development of educational programs designed to reinforce those standards, and the public recognition of responsible conduct on the part of scientists. PMID- 7983264 TI - Ethics and dental research. AB - Dentistry is a Hippocratic profession and is therefore committed to ongoing research into the causes and treatments of disease. This research embodies ethical standards which place a high value on a respect for persons. Those standards emphasize that we obtain informed consent from individuals selected to participate in research. The relevant information required for informed consent varies from situation to situation but should take into account the need for participants to make a reasoned decision about their involvement. Where community research is involved, there should be consultation with appropriate representatives. In all contemporary medical research, there is an inherent conflict between the ethical requirement that we share information which will help those who are suffering and the need to preserve rights to competitively sensitive information related to product development and academic funding. These various pressures on research emphasize the need for an active and lively appreciation of ethical issues in contemporary biomedical sciences. PMID- 7983265 TI - Ethics in dental research. Ethical use of animals. AB - Based on old nursery rhymes, which are still in vogue, it is apparent that children from an early age receive ambivalent messages concerning relationships with animals. It is also apparent that we as a society have placed a hierarchical structure on animals; it is clear that we value a dog or a cat more than a mouse or a rat. Enormous strides in the prevention and treatment of disease have been made directly or indirectly as a result of experiments carried out on animals. Persons who conduct investigations using animals have an obligation to ensure that valid scientific questions are being explored, and that the minimum numbers of animals are used compatible with achieving a valid scientific result. Animals must always be cared for properly. Research involving induction of pain must receive particular attention. Finally, it is incumbent upon all scientists who use animals in their investigations to ensure that the public is kept fully informed of all scientific advances made by the use of animals. PMID- 7983267 TI - Ethics in dental research. Toward developing a code of ethics. AB - A profession is considered to be ethical by its very nature. Hence, the ability to structure a set of principles that gives one a way to discuss the issues is crucial. However, numerous variables--such as culture, tradition of law, and stage of technological development of a Nation-State--confound issues in which principles may occasionally clash. There may not always be a right and wrong. Hence, for an international organization, a clear explanation of rules will be critical in the development of a code of ethics. PMID- 7983266 TI - Ethics in dental research. Publication of research: the ethical dimension. AB - If science is to achieve its goal, i.e., advancement of human well-being, the results of scientific research must be made available. When such results are presented, that presentation must be 'ethical'; it must conform to recognized standards of honesty, originality, and fairness. Unfortunately, not all such presentations conform to these standards; the public and scientific community alike are becoming ever more concerned about duplication in publication, about illegitimate claims to authorship, and about misleading use of statistics in presentation of experimental results. Certain of these 'unethical' practices can be eliminated or minimized by education, institutional practice, and requirements set by scientific journals. In the end, however, 'ethical publication' will depend on the 'ethical investigator'--an individual who has professed dedication to truth and the well-being of mankind. PMID- 7983268 TI - Descending frequency swept tones have lower thresholds than ascending frequency swept tones for a harbor seal (Phoca vitulina) and human listeners. AB - Many seal vocalizations consist of frequency swept tones. The signal detection thresholds of a harbor seal (Phoca vitulina) and of human listeners were measured using ascending and descending frequency swept tones at 1/3- and 1-oct bandwidths. The swept tones increased or decreased exponentially and traversed the same frequency range. The sweeps were centered on 2, 4, and 8 kHz for the seal study and 0.5, 1, and 2 kHz for the human listeners. The bandwidth of the sweep did not affect signal detection abilities of either the seal or human listeners. The seal had lower signal detection thresholds (1-5 dB) when presented with the descending frequency swept tones (F = 32.04, df = (1,31), p < 0.000001). Human listeners also had lower detection thresholds for descending frequency swept tones (t = -4.78, df = 52, p < 0.0001). Pinniped ascending frequency swept calls may not function as well as descending frequency sweeps for long-distance communicative signals. PMID- 7983269 TI - Tone recognition of continuous Mandarin speech assisted with prosodic information. AB - In this paper, a simple recurrent neural network (SRNN) is employed to model the prosody of continuous Mandarin speech to assist tone recognition. For each syllable in continuous speech, several acoustic features carrying prosodic information are extracted and taken as inputs to the SRNN. If proper linguistic features extracted from the context of the syllable are set as output targets, the SRNN can learn to represent the prosodic state of the utterance at the syllable using its hidden nodes. Outputs of the hidden nodes then serve as additional recognition features to assist recognition of the tone of the syllable. The performance of the proposed tone recognition approach was examined by simulation on a multilayer perception (MLP)-based speaker-dependent tone recognition task. The recognition rate was improved from 91.38% to 93.10%. The SRNN prosodic model is further analyzed to exploit the linguistic meaning of prosodic states. By vector quantizing the outputs of the hidden nodes of the SRNN, a finite-state automata that roughly represents the mechanism of human prosody pronunciation can be obtained. PMID- 7983270 TI - Longitudinal research on adolescent voice change in males. AB - Many of the characteristics and processes associated with adolescence are reasonably well understood; others are not. Still unanswered are questions about adolescent voice change. For example, when does the average child start the process; what changes result and what is their extent; when is it complete? Further, how closely do shifts in vocal level parallel, or even predict, the adolescent process? This project was carried out in order to obtain data which would complement available information on the subject and provide additional specificity about voice change and pubescence--at least for boys. To that end, a longitudinal study was conducted in which 48 males were tracked over a 5-year period. Voice measurements were made--including speaking fundamental frequency (SFF) and phonational frequency range (PFR)--as were others relating to physical size (height, weight, and six body dimensions). It was found that (1) stable adolescent voice change (AVC) measurements could be obtained, (2) maturation patterns appeared predictable on the basis of AVC changes, and (3) both the onset and duration of voice change extended over a longer period of time than had been previously thought. PMID- 7983271 TI - Relation between the growth of loudness and high-frequency excitation. AB - To test the conjecture that cochlear impairment and a masking noise in normal ears produce analogous effects on the growth of loudness, loudness was measured for 21 listeners, all with bilateral symmetrical high-frequency cochlear losses. Beyond the normal-hearing region, thresholds increased by 30-49 dB/octave for 10 listeners in group I and by 51-71 + dB/octave for 11 listeners in group II. Measured by absolute magnitude estimation and production at two frequencies where thresholds were normal, the dynamic range over which loudness grows was not altered by the adjacent hearing loss. This was not true however, for the slope. Whereas the overall shape and slope of the loudness functions were essentially the same for group I, the mid-to-high level slope for group II was noticeably flatter for a tone at the cutoff frequency than for a lower-frequency tone. In contrast, markedly steeper loudness functions, characteristic of loudness recruitment, were obtained for both groups at a frequency in the region of impaired hearing. The reduced rate of loudness growth observed in the region of normal hearing for listeners with steep low-pass losses, like the reduction usually found for a tone masked by an adjacent high-frequency noise, is ascribed to the tone's restricted excitation pattern. These results indicate that high frequency auditory cues are effectively eliminated by a steeply sloping high frequency hearing loss just as they are eliminated by the addition of an external noise. PMID- 7983272 TI - Pitch percepts associated with amplitude-modulated current pulse trains in cochlear implantees. AB - The percepts elicited by electrical stimulation of auditory neurons by trains of amplitude-modulated current pulses were studied in a group of six cochlear implant users. Modulation frequencies of 100, 150, and 200 Hz were studied, with a range of carrier rates up to 1200 Hz. It was found that all but one subject could consistently rank 150- and 200-Hz modulated stimuli by modulation frequency when the carrier rate was more than 800 Hz, but for lower carrier rates the ranking was greatly affected by the harmonic relationship between carrier and modulation frequency. Pitch matching experiments showed that the subjects generally considered the modulated stimuli to be equal in pitch to unmodulated stimuli with rates the same as, or somewhat higher than, the modulation frequency. The results showed that the "pitch" of pulsatile electrical stimulation resulting from periodicities in the time structure of the electrical stimulus has similarities to the "pitch" observed for temporal patterns in acoustic stimulation such as amplitude-modulated noise. There were some differences, however, which may be attributable at least in part to the physiological response differences for electric and acoustic stimulation. PMID- 7983273 TI - Comodulation masking release for elderly listeners with relatively normal audiograms. AB - Thresholds for the detection of a 1.0-kHz pure tone were measured in modulated and unmodulated noise for a group of nine elderly listeners, aged 62-83, with normal or near-normal audiograms, and a reference group of seven younger normal hearing listeners. The masker was either a band of noise 128 Hz wide [approximately one equivalent rectangular bandwidth (ERB) centered at 1.0 kHz], or a band of noise 1505 Hz wide (approximately five ERBs above and five ERBs below 1.0 kHz). The noise was either unmodulated or was square-wave modulated at rates of 10, 20, 30, 40, and 50 Hz. A measure of comodulation masking release (CMR) was derived from the masking data. Because wider filters have been found to be associated with reduced CMR, auditory filter shapes were also estimated for the elderly listeners. The filters were found to be normal at the center frequencies of 800, 1000, and 2000 Hz ruling out possible confounding effects of impaired auditory filters on CMR. Masked detection thresholds were generally significantly higher for the elderly as compared to the younger listeners for both unmodulated and modulated noise. Thresholds were lower in modulated as compared to unmodulated noise masking for both elderly and young listeners. For both groups of listeners and for both narrow- and wideband masking, detection thresholds continued to increase as modulation rates were increased. CMR was not different for the elderly and young listeners and it was similarly decreased, for both groups, at higher rates of modulation. PMID- 7983275 TI - Resetting the pitch-analysis system. 2. Role of sudden onsets and offsets in the perception of individual components in a cluster of overlapping tones. AB - Experiments on young adults studied the effects of suddenness of onset or offset on the discrimination of the order of pitches of individual tones in a 1-s, 4 tone cluster of overlapping pure tones. In experiment 1, the tones, all within a critical band, went on asynchronously. Each rose and decayed linearly in amplitude. Faster onsets, within the range 10 to 640 ms as measured on the first tone, increased the accuracy of the discrimination of the order of onsets, but 10 ms onsets were slightly worse than 40-ms onsets in early sessions. Experiment 2 found similar effects for the abruptness of offsets of tones in clusters whose components came on synchronously but went off asynchronously. Onset order was very much easier to detect than offset order. The auditory system may use neural onset and offset responses to reset itself and carry out new analyses at frequency-by-amplitude points of sudden amplitude change, thereby contributing to auditory scene analysis. PMID- 7983274 TI - Intensity discrimination in normal-hearing and hearing-impaired listeners. AB - Weber fractions (delta I/I) for gated 500-ms tones at 0.3, 0.5, 1, 2, and 3 kHz, and at levels of the standard ranging from absolute threshold to 97 dB SPL, were measured in quiet and in high-pass noise in five listeners with cochlear hearing loss and in three normal-hearing listeners. In regions of hearing loss, the Weber fractions at a given SPL were sometimes normal. When the Weber fractions were normal or near-normal, the addition of high-pass noise elevated the Weber fraction, strongly suggesting the use of spread of excitation to higher frequencies. Inversely, when the Weber fractions were elevated, the addition of high-pass noise produced no additional elevation, suggesting an inability to use spread of excitation. In general, the relative size of the Weber fractions, the effects of high-pass noise, and to a lesser extent, the dependence of the Weber fraction on level, were consistent with expectations based upon the audiometric configuration and the use of excitation spread. There were several notable inconsistencies, however, in which normal Weber fractions were seen at a frequency on the edge of a steep high-frequency loss, and in which elevated Weber fractions were observed in a flat audiometric configuration. Finally, when compared at the same SL, the Weber fraction was sometimes smaller in cochlear impaired than in normal hearing listeners. This was true even in high-pass noise, where excitation spread was limited, and may reflect the unusually steep rate versus level functions seen in auditory nerve fibers that innervate regions of pathology. PMID- 7983276 TI - Frequency and frequency-ratio resolution by possessors of absolute and relative pitch: examples of categorical perception. AB - The methodology derived from the trace-context theory of intensity resolution (Durlach and Braida, 1969; Macmillan et al., 1988) was applied to resolution over an octave range along two continua: a sequential-frequency-ratio continuum for possessors of relative pitch (RP), and a pure-tone frequency continuum for possessors of absolute pitch (AP). The performance of both RP and AP possessors was exceptional in that total identification sensitivity along both continua was much greater than identification sensitivity along unidimensional psychophysical continua characterized by the 7 +/- 2 rule. In addition, the performance of RP possessors was exceptional in that, on average, total sensitivity for identification resolution was greater than sensitivity for resolution in discrimination. Finally, identification sensitivity between category prototypes (chromatic semits) along both continua was approximately the same as identification sensitivity between phonemic category prototypes along speech continua, despite the fact that both the discrimination ranges and the total number of categories are much larger for the two pitch continua. PMID- 7983278 TI - Temporal pattern discrimination and speech recognition under electrical stimulation. AB - Discrimination of temporal patterns has been suggested as a relevant process in speech recognition by subjects with normal hearing [Sorkin, J. Acoust. Soc. Am. 87, 1695-1701 (1990)]. This paper investigates whether performance of Nucleus multichannel cochlear implant subjects on a temporal pattern discrimination task is an efficient and valid psychophysical measure of speech recognition ability. Stimuli consisted of temporal sequences defined by twelve 35-ms tones and eleven randomly generated temporal gaps separating the tones. A fixed-level same/different paradigm was used to measure the discriminability of these sequences as a function of their average correlation across a block of trials. On each trial, the "standard" sequence was generated randomly by drawing gap durations from a Gaussian distribution. The gaps of the comparison sequence were generated in a similar fashion with a specified average correlation with the gaps of the first sequence. Performance of implanted and normal hearing subjects decreased monotonically with increasing average sequence correlation. However, performance across implanted subjects ranged from that observed for acoustically stimulated subjects with audiometrically normal hearing to levels near chance. Comparing these data with measures of speech recognition in the same subjects, we have found that performance on standard speech recognition tests correlates with ability to discriminate among such random temporal patterns. PMID- 7983277 TI - Stimulus classification procedure for assessing the extent to which binaural processing is spectrally analytic or synthetic. AB - A two-dimensional stimulus classification paradigm was used to assess the extent to which listeners' processing of interaural delays at low frequencies is spectrally analytic or synthetic. Listeners were presented with a 753-Hz target with an interaural delay that varied from trial to trial, taking on one of ten values, five leading to the left ear and five leading to the right. A 553-Hz distractor component was simultaneously presented, with its interaural delay also presented at one of ten different values. During a block of 100 trials, each of the possible combinations of target and distractor delay was presented once, and only once, in a random order. Listeners were instructed to make left-right judgments based on the target delay. Each condition was repeated ten times, and the slopes of the best linear boundaries between left and right responses were used to derive the relative weights given to the target and distractor in judgments of laterality. Six of the nine listeners gave increasing weight to the target as the duration of the signals was increased from 25 or 50 to 400 ms. Three listeners showed little change with duration; one consistently gave equal weight to the target and distractor, two consistently gave greater weight to the target than to the distractor. The utility of classification paradigms in the study of multidimensional acoustic signals is discussed. PMID- 7983279 TI - Temperature dependence of two-tone rate suppression in the northern leopard frog, Rana pipiens pipiens. AB - The existence region of two-tone rate suppression in frog low-frequency auditory nerve fibers was found to include a suppressive region below a fiber's characteristic frequency, contrary to previous reports. In response to 3 degrees C rise in core temperature, the area and the best suppressive frequency (BSF) of the low-side suppressive region significantly increased. Increasing core temperature of the frog by 6 degrees C resulted in significant changes in the high-side suppressive region: Its area decreased, and its BSF and best suppressive threshold (BST) increased. Constant-temperature control trials were designed to partially simulate the relative movement of the probe tone within the excitatory tuning curve which occurred during temperature shifts. Lowering the probe tone by 0.5 oct had no effect on the low-side suppressive region, but significantly increased the area and lowered the BSF and BST of the high-side suppressive region. Temperature shifts in the frog appear to have a differential effect on the low-side and high-side suppressive areas of low-frequency auditory nerve fibers. Moreover, excitation and suppression also respond differentially to temperature shifts. PMID- 7983280 TI - Evaluating residual background noise in human auditory brain-stem responses. AB - The nature of the residual background noise in ABR averages was empirically examined in normal hearing objects. The residual noise in the average was estimated with use of the technique described by Elberling and Don [Scand. Audiol. 13, 187-197 (1984)]. Low-level click stimuli were presented in 2-dB steps spanning the range from 30 to 48 dB p-p.e. SPL. For each stimulus level, 10,000 sweeps were acquired and stored for analysis. Shortcomings of the use of artifact rejection and standard averaging are demonstrated. It is further demonstrated how application of the Bayesian estimation technique of Elberling and Wahlgreen [Scand. Audiol. 14, 89-96 (1985)] to form weighted averages can help minimize these shortcomings. Finally, the effects of smaller sweep block sizes on the Bayesian technique's ability to control the destructive effects of nonstationary noise are analyzed. Minimizing the destructive effects increases the value of statistical techniques used to detect objectively or to control the quality of ABR recordings. In all, these techniques in combination improve not only the accuracy of test interpretation but also the efficiency of clinical test time, which is becoming important for the control of medical costs. PMID- 7983281 TI - Discrimination of speech-like contrasts in the auditory thalamus and cortex. AB - The neurophysiologic discrimination of acoustic contrasts was investigated as reflected by the mismatch negativity (MMN) response. Evoked responses were recorded from guinea pig thalamus (medial geniculate nucleus) and epidural surface in response to synthesized speech contrasts /ga/-/da/ and /ba/-/wa/. From the caudomedial portion of the medial geniculate nucleus, /ba/-/wa/ elicited a strong mismatch response, whereas /ga/-/da/ did not. Neither stimulus contrast elicited an MMN from the ventral, or primary, portion of medial geniculate. Both stimulus contrasts elicited an MMN from the midline surface. Neither contrast elicited an MMN from the surface over the temporal lobe. Results indicate a hierarchy of processing of the spectrotemporal changes which characterize formant transitions. Also, results indicate that the nonprimary portions of the auditory pathway contribute substantially to the MMN. PMID- 7983282 TI - Modeling the Dornier HM3 lithotripter. AB - The computational modeling of a Dornier HM3 electrohydraulic, extracorporeal shock wave lithotripter is considered. In order to produce large amplitude shock waves for the purpose of pulverizing renal and ureteric calculi (stones), the HM3 uses a hemi-ellipsoidal bowl to focus the spherical field generated by a high voltage spark gap. The initial propagation of the bowl-focused field is accomplished using a recently developed nonplanar source algorithm. An updated version of an existing nonlinear acoustic beam propagation model is then used to consider the subsequent propagation of the field. The resulting modeling sequence accounts for the effects of diffraction, attenuation, dispersion, nonlinearity, and (planar) reflection and refraction. The water path computed predictions agree well with existing measurements. The computed in vivo predictions suggest that the Dornier HM3's clinical performance is not significantly different than its water path performance. PMID- 7983283 TI - Geriatric home assessment after hospital discharge. AB - OBJECTIVES: To evaluate the feasibility of an intervention involving post discharge geriatric home assessment and follow-up and to describe the spectrum of significant clinical problems identified during the home assessment. DESIGN: Prospective observational study nested within a randomized controlled trial. SETTING: Inpatient service of a large academic medical center in Southern California. PATIENTS: There were 152 adults aged 65 or greater who had one or more specific risk factors for functional decline or increased mortality, who were awaiting discharge from the hospital, and who were assigned to the intervention arm of a randomized controlled trial of post-discharge comprehensive geriatric home assessment. MAIN RESULTS: During the home assessment, the gerontologic nurse practitioner (GNP) identified new or worsening problems in 150 patients (99%); 61 problems (eg, serum sodium 125 mg/dL; severe orthostatic hypotension) were considered by a reviewing physician to require urgent medical attention. Older age, non-white race, and new incontinence were associated independently with a greater number of findings (P < 0.05). Based on the findings, an interdisciplinary team made an average of 3.4 recommendations per patient; only two of 111 requests for written approval of recommendations were rejected. CONCLUSIONS: Post-discharge visitation by a GNP to patients at high risk is capable of detecting a high yield of important and potentially reversible clinical problems. This multidisciplinary approach is acceptable to physicians. Research is needed to identify additional links between short hospital stays, impairment or instability at discharge, and adverse outcomes. PMID- 7983285 TI - Appropriateness of medication prescribing in ambulatory elderly patients. AB - OBJECTIVE: To assess the quality of medication prescribing in ambulatory elderly patients on multiple medications using the Medication Appropriateness Index (MAI). DESIGN: Cross-sectional study. SETTING: General Medical Clinic of the Durham VA Medical Center. PATIENTS: 208 elderly outpatients on five or more regularly scheduled medications. MEASUREMENTS: Medication prescribing appropriateness was measured with the MAI, a reliable method that employs 10 implicit criteria. A weighted MAI score (range 0-18 per drug) served as a summary measure of appropriateness. RESULTS: There were 1644 medications evaluated; 26% received no inappropriate ratings, 37% had one, 19% had two, and 18% had three or more. Of 16,440 ratings, 2295 (14%) were evaluated as inappropriate. The percentage of inappropriate ratings varied across prescribing dimensions: drug drug interactions, 0%; drug-disease interactions, 1.4%; medication effectiveness, 4.7%; therapeutic duplication, 5.7%; indication, 11.5%; duration of treatment, 16.5%; dosage, 17.3%; practical directions, 20.3%; cost, 29.7%; and correct directions, 32.4%. The mean MAI score for all medications was 2.2 +/- 2.1 (range 0-10) and varied by therapeutic class. MAI scores were significantly lower for medications with a high potential for adverse effects compared with those with a low potential (MAI score of 1.8 vs 2.9, P < 0.001). Regression analysis revealed that no patient characteristics were associated with a higher likelihood of inappropriate prescribing. CONCLUSIONS: Medication prescribing for elderly outpatients taking multiple medications was substantially appropriate. Prescribing dimensions with the most room for improvement were more exact directions, less expensive drugs, and practical directions. Drugs at high risk for adverse effects were prescribed more appropriately than those at low risk. PMID- 7983284 TI - Risk factors for non-insulin-dependent diabetes mellitus requiring treatment in the elderly. AB - OBJECTIVE: To examine the relationship of possible modifiable risk factors, including obesity, physical activity level, alcohol consumption, blood pressure, and thiazide diuretic use with the development of non-insulin-dependent diabetes mellitus (NIDDM) requiring treatment among a large cohort of community-dwelling elderly. SETTING: The East Boston Senior Health Project, one of four components of the National Institute on Aging-sponsored Established Populations for the Epidemiologic Study of the Elderly (EPESE). PARTICIPANTS: Residents of East Boston who were 65 years of age or older. MEASUREMENTS: We performed a prospective cohort study with follow-up over two consecutive 3-year time periods beginning in 1982-1983. The main outcome measure was the occurrence of NIDDM, defined as new treatment with a hypoglycemic agent. A total of 2737 study participants contributed 4682 3-year intervals for analysis. MAIN RESULTS: NIDDM requiring hypoglycemic therapy occurred in 185 participants over the duration of the study. High body mass index (> 26 kg/m2) (adjusted odds ratio 2.4, 95% confidence interval 1.3-4.4) and low physical activity level (adjusted odds ratio 1.5, 95% confidence interval 1.0-2.1) were significant predictors of NIDDM in a multiple logistic regression model adjusting for age, sex, blood pressure, and self-report of "high blood sugar" moderate alcohol consumption (0.5-<1 ounce per day) had an inverse relation to NIDDM of borderline significance (adjusted odds ratio 0.4, 95% confidence interval 0.2-1.0). Those receiving one or more non thiazide antihypertensive agents had a higher risk of developing NIDDM in a model including age, sex, body mass index, various antihypertensive regimens, physical activity level, alcohol consumption, blood pressure, and self-report of "high blood sugar." Thiazide diuretic therapy alone or in combination with another antihypertensive was not associated with NIDDM. CONCLUSIONS: Our findings suggest a positive relationship of obesity and low physical activity level with the development of NIDDM requiring treatment in elderly persons. The inverse association of borderline significance between moderate alcohol use and NIDDM deserves further study. Thiazide diuretic therapy conferred no excess risk for developing NIDDM in this older population although selection factors in the choice of antihypertensive therapy may partially explain the absence of a thiazide effect. PMID- 7983286 TI - Incidence of complications after carotid sinus massage in older patients with syncope. AB - OBJECTIVE: To review the incidence of neurological complications occurring after carotid sinus massage performed for diagnostic purposes. DESIGN: Case review and comparison with previously published work. SETTING: Syncope Clinic, Royal Victoria Infirmary, Newcastle-upon-Tyne, and Chelsea and Westminster Hospital, London. PARTICIPANTS: Patients undergoing investigation of dizziness, syncope, or unexplained falls. METHODS: Carotid sinus massage performed for 5 seconds in both supine and erect postures, both before and after atropine. Contraindications to carotid sinus massage were the presence of carotid bruits, recent myocardial or cerebral ischemia, or previous ventricular tachyarrhythmias. RESULTS: Two cases of neurological complications were reported from a total of 500 patients (2000 massage episodes) investigated in one center, giving an incidence of 0.1%. Combining this data with another center performing investigations in a similar fashion, seven neurological complications arose from a total of 5000 massage episodes, an incidence of 0.14%. Reported complications were pyramidal signs in five cases and visual field defects in two. Pyramidal weakness persisted in one case with a pre-existing stroke on the same side, and a visual field loss was permanent in one. CONCLUSIONS: Neurological complications following carotid sinus massage for diagnosis of the carotid sinus syndrome are uncommon and usually transient. Contraindications to carotid sinus massage should be respected and the standardized technique used. PMID- 7983287 TI - Characteristics of nonresponders in a community survey of the elderly. AB - OBJECTIVE: To identify predictors of nonresponse in a community survey of cognitive status in the elderly. DESIGN: Cross-sectional community survey with two stages of recruitment: an initial, less-intensive method, followed by a more aggressive approach that included face-to-face contact. Characteristics of initial nonresponders and responders were compared. SETTING: A close-knit rural community with higher than usual proportions of elderly, especially the very old. Subjects were interviewed in their homes. Collateral informants were subsequently interviewed by telephone. PARTICIPANTS: Utah heads of household aged 75 and older who resided in a noninstitutionalized setting. MEASUREMENTS: Mini-Mental State Examination (MMSE), Dementia Questionnaire, and an autobiographical risk factor and family history questionnaire provided measures for all independent variables. The dependent variable was status as initial responders or initial nonresponders. RESULTS: An initial participation rate of 63% was achieved, but a final rate of 93% was achieved when initial nonresponders were contacted later face-to-face. MMSE score was significantly related to responder status when analyzed alone (beta = -.19, P = 0.02) and remained a significant predictor after adjusting for education and whether born in Cache County (beta = -.16, P = 0.041) or current drinking, diabetes, or "other" health problems (beta = -.18, P = 0.028). After controlling for the informant report of subject's problems with activities of daily living, MMSE score fell just below statistical significance (beta = -.16, P = 0.079). CONCLUSIONS: Nonresponders in community surveys of the elderly appear to be disproportionately cognitively impaired. The increase in participation rates achieved after more persistent recruitment suggests that many initial nonresponders can still be recruited if intensive methods are used. PMID- 7983288 TI - Urinary incontinence knowledge among community-dwelling people 65 years of age and older. AB - OBJECTIVES: We determined elderly persons' knowledge about the epidemiology and treatment of urinary incontinence (UI) as part of a preintervention survey for the Educational Demonstration of Urinary Continence Assessment and Treatment for the Elderly (EDUCATE). DESIGN: An intact-group pretest-posttest design was employed to measure the effects of multimethod educational interventions on the knowledge, attitudes, and practices of physicians and older people concerning UI. PARTICIPANTS: A random sample of community-dwelling people aged 65 years and older from two counties in Massachusetts was selected (n = 1,140). MEASUREMENT: A 14-item urinary incontinence quiz was developed from information presented in the AHCPR UI Guideline Panel's recommendations. Participants answers to the quiz were part of a 20-minute telephone interview. RESULTS: For nine of the fact items, the elderly respondents were more likely to give the correct answer than the incorrect answer. However, for only four of those nine did the percentage of correct responses exceed 50% (there were substantial proportions of "don't know" responses). For several fact items, those who were younger, female, or had more formal education were more likely to provide correct responses. CONCLUSIONS: There are substantial gaps in the knowledge of older persons about urinary incontinence, especially among men, those age 85 and older, and those with lower levels of education. These knowledge gaps may contribute to misinterpretation of symptoms and underreporting of symptoms to health care professionals. This pattern of findings indicates a greater need for community education on urinary incontinence. PMID- 7983289 TI - Prostaglandin E1 as treatment for erectile failure in elderly men. AB - OBJECTIVE: To determine the efficacy of intracavernosal injection of prostaglandin E1 (alprostadil) in elderly men with erectile failure. DESIGN: Prospective study. SETTING: Outpatients at a university-affiliated VA Medical Center. PARTICIPANTS: Ten subjects aged 65 years and older with duration of erectile failure of 6 months or longer. INTERVENTIONS: Subjects received intracavernosal injections of prostaglandin E1 in the office and self administered intracavernosal prostaglandin E1 at home. MEASUREMENTS: Penile rigidity was measured by palpation and by the Rigiscan rigidity monitor. RESULTS: Intracavernosal injection of prostaglandin E1 produced erections adequate for intercourse in 9 of the 10 subjects. Attempts at intercourse were rated satisfactory by two-thirds of the subjects and their spouses. CONCLUSIONS: Intracavernosal injection of prostaglandin E1 is safe and effective for erectile failure in elderly men. PMID- 7983290 TI - The neglected half of Alzheimer disease: cognitive and functional concomitants of severe dementia. AB - OBJECTIVE: Traditional mental status and psychometric assessments bottom out in the late stages of Alzheimer disease (AD). A method adapted from cognitive testing in infants, the Ordinal Scales of Psychological Development was modified (M-OSPD) and applied to a severely demented population. The concurrent validity of this method was tested in comparison with Functional Assessment Staging (FAST). Internal consistency as a measure for reliability was also determined. DESIGN: Cross sectional study. SETTING: Subjects were generally evaluated in their residence, usually a nursing home or a private home. PATIENTS: Severely cognitively impaired subjects who fulfilled criteria for probable AD were studied. MEASUREMENTS: Evaluation consisted of clinical global, mental status, functional, and cognitive assessments including the Global Deterioration Scale (GDS) and the Mini-Mental State Examination (MMSE). RESULTS: Seventy patients were evaluated. Traditional mental status assessments (eg, the MMSE) manifested virtually uniform bottom scores in all GDS stage 7 subjects (n = 46), and GDS stage 6 subjects had MMSE scores within one standard deviation unit of zero. In contrast, the M-OSPD scale continued to show results in the last stages of the disease. The Spearman correlation coefficient between the M-OSPD total score and the 11 FAST substages represented in this sample was -0.77 (P < 0.001). CONCLUSIONS: The results indicate that patients who are functionally more impaired also show continuing increments in cognitive loss. These cognitive and functional assessments for measuring the magnitude of deterioration in AD can be applied to the estimated half-million nursing home residents presently labeled "untestable" with the goal of optimization of care and residual capacities. PMID- 7983291 TI - A multi-center analysis of the use of enalapril and lisinopril in elderly hypertensive patients. AB - OBJECTIVE: To evaluate the clinical use and adverse effects of enalapril and lisinopril in elderly hypertensive subjects. DESIGN: A multi-center, retrospective, drug use evaluation survey. SETTING: Ambulatory care clinics at 14 VA and 14 academic medical centers. PATIENTS: 422 elderly (> 60 years of age) patients with hypertension and no clinical evidence of congestive heart failure. INTERVENTION: At least 3 consecutive months of anti-hypertensive therapy with either enalapril or lisinopril. MEASUREMENTS: Blood pressure, serum creatinine, serum potassium, concomitant disease states, concurrent medications, and documentation of any adverse event that might be related to ACE inhibitor therapy. RESULTS: There were no significant differences in systolic and diastolic blood pressures, serum creatinine, or serum potassium between enalapril- and lisinopril-treated patients at baseline and after 3 months of therapy. Both treatments resulted in a significant reduction in diastolic blood pressure. There was no significant difference in the incidence of adverse effects between the two treatments. Significantly more patients were dosed on a twice daily regimen of enalapril than lisinopril. CONCLUSION: The data from this retrospective study confirm the safe and effective use of enalapril and lisinopril, two long-acting ACE inhibitors, in elderly hypertensive patients. PMID- 7983292 TI - Emergency triage to intensive care: can we use prognosis and patient preferences? AB - OBJECTIVE: To identify predictors of 6-month mortality known before emergent admission to intensive care (IC) and to describe obstacles to the use of patient preferences in emergency triage decisions. DESIGN: Historical cohort. SETTING: A 600-bed university hospital. PATIENTS: 263 consecutive patients triaged in the emergency room to receive intensive care. MEASUREMENTS AND MAIN RESULTS: Medical records were abstracted for age, performance status, and chronic disease severity as predictors of 6-month survival. Acute Physiology Score (APS) in the emergency room was used as a measure of acute illness severity. Deaths during the 6 months following IC admission were determined from record review and death certificate data. Obstacles to communication of patient treatment preferences at the time of triage were described. Six-month mortality was 19 percent, and increased with increasing APS, age > or = 80 (43%), poor performance status (56%), and severe chronic disease (33%) (P < or = 0.01). In multivariate analysis, APS, age > or = 80 and performance status were independent predictors of 6-month mortality. Only APS predicted mortality in hospital. The most common obstacles to use of patient preferences in triage decisions were absence of documented advance directives (95%) and the brief duration of acute illness (72%). Mental status changes were very common in the emergency room for nonsurvivors (61%), but chronic cognitive impairment was rare (3%). CONCLUSIONS: Patients with poor performance status or very advanced age have increased mortality within 6 months of emergent triage to IC. Mental status changes, absence of advance directives, and time constraints are common barriers to communication of patient preferences at the time of triage. Primary care physicians need to elicit and record patients' preferences before the time of emergent decisions about IC. PMID- 7983293 TI - Rehospitalization rates in older depressed adults after antidepressant and electroconvulsive therapy treatment. AB - OBJECTIVE: To determine (1) if a "high risk" period for rehospitalization can be identified in a population of depressed older adults and (2) if age of onset and previous history of depression is associated with an increased risk of rehospitalization. DESIGN: Naturalistic, longitudinal treatment outcome study. SETTING: Medical-psychiatry unit and outpatient clinic at a university hospital. PATIENTS: Ninety-four older adults diagnosed with major depression based on SCID and DSM-III-R criteria who were hospitalized for treatment. INTERVENTIONS: All patients were initially hospitalized on a medical-psychiatry unit and treated with either antidepressants or electroconvulsive therapy. MEASUREMENTS: Patients were initially evaluated with the Structured Clinical Interview for DSM-III-R (SCID), the Hamilton Depression Rating Scale, and a battery of neuro psychological and behavioral tests. Patients were followed over time with an average follow-up interval of 3.09 + 1.45 years, and the date of the first psychiatric rehospitalization (if any) was recorded. RESULTS: Approximately 43.6 percent of the total sample required at least one psychiatric rehospitalization. The greatest risk of rehospitalization occurred in the first 18 months. No significant differences were noted between patient groups treated with ECT and those treated with antidepressants or between patients with a younger and those with an older age of onset of depressive disorder. A statistical trend was observed in which patients without previous episodes of depression had a lower overall rate of rehospitalization compared with patients with one or more previous episodes of depression. CONCLUSIONS: There appears to be a relatively high risk of psychiatric rehospitalization in depressed older adults, particularly in the first 18 months. This rate of rehospitalization underscores the importance of providing maintenance therapy and intensive psychiatric supervision for a minimum of 18 months to 2 years during the course of a depressive episode requiring inpatient hospitalization. PMID- 7983294 TI - Long-term urethral catheterization increases risk of chronic pyelonephritis and renal inflammation. AB - OBJECTIVE: To determine the prevalences of chronic pyelonephritis and chronic renal inflammation in elderly nursing home patients at the time of death and to assess correlation with urethral catheterization and other putative risk factors. DESIGN: Prospective assessment of risk factors with the prevalences of chronic pyelonephritis and renal inflammation at autopsy. SETTING: A 240-bed long-term care facility. PARTICIPANTS: All residents > or = 65 years old who died and were autopsied during a 2-year period. MEASUREMENTS: Antemortem assessment of risk factors for renal inflammation, including a search for any urethral catheterization in the person's life. Prospective assessment of urethral catheterization, catheter obstruction, and use of anti-inflammatory medications and urine cultures. Urinary tract pathology was assessed for gross and microscopic evidence of inflammation and urinary tract stones. RESULTS: The duration of catheterization was significantly associated with increasing prevalence of bacteriuria, polymicrobial bacteriuria, chronic pyelonephritis, and chronic renal inflammation. The prevalence of chronic pyelonephritis at death was 10 percent (5/52) for patients catheterized > 90 days during their last year of life and zero (0/65) when catheterized < or = 90 days (P < 0.02; Fisher's exact test). Chronic pyelonephritis was significantly associated with renal stones and hydronephrosis. The prevalence of chronic renal inflammation without chronic pyelonephritis was significantly greater than that of chronic pyelonephritis: the prevalence was 43 percent (20/47) when catheterized > 90 days and 18 percent (12/65) when < or = 90 days (P < 0.05). Chronic renal inflammation was associated with hydronephrosis, ureteral dilatation, acute pyelonephritis and diastolic hypertension. CONCLUSION: Chronic pyelonephritis and chronic renal inflammation are associated with long-term catheterization. PMID- 7983295 TI - Idiopathic CD4+ T lymphopenia in older persons. AB - OBJECTIVE: Survey of the association of idiopathic CD4+ T cell lymphocytopenia in older persons with protein energy undernutrition and unusual infections/colonizations. METHOD: Retrospective chart analysis. RESULTS: Five subjects aged 61 to 87 years, with unusual organisms and/or either marasmus or kwashiorkor, were noted to have absolute CD4+ and CD8+ T cell lymphocytopenia. All were HIV negative. CONCLUSION: T cell lymphocytopenia may not be a uncommon finding in malnourished older persons, but additional studies to determine its prevalence need to be undertaken. Its role in disease and impact on therapeutic response needs to be further explored. PMID- 7983297 TI - Echocardiography should be performed in all elderly patients with congestive heart failure. PMID- 7983296 TI - Assessing health-related quality of life in elderly outpatients: telephone versus face-to-face administration. AB - OBJECTIVE: While health-related quality of life (HRQOL) is increasingly being used as an outcome in clinical trials, it is unknown whether HRQOL assessments are influenced by the method of administration. Within the context of a randomized, controlled trial evaluating a pharmacist intervention for elderly outpatients prescribed at least five medications, we compared telephone and face to-face administration of the SF-36, a widely used HRQOL measure. DESIGN: Survey. SETTING: General Medicine Clinic, Veterans Affairs Medical Center. PATIENTS: At entry, participants in the randomized trial received continuous care from a general medicine clinic physician, were > or = 65 years of age, and were prescribed > or = 5 regularly scheduled medications. Patients were excluded if they were cognitively impaired and had no caregiver available to participate in the study as a proxy or if they resided in a nursing home. MEASUREMENTS: Subjects completed the SF-36 by telephone at closeout and face-to-face at clinic visits within 1 month (mean = 16.7 days). MAIN RESULTS: Telephone administration required significantly less time than face-to-face interviews (10.2 vs 14.0 minutes, P < 0.001). Although systematic differences between modes of administration were generally small, there were substantial nonsystematic discrepancies for all eight SF-36 scales (mean absolute difference scores ranged from 10.8 to 30.1). Discrepancies were greatest for emotional role functioning, physical role functioning, social functioning, and bodily pain; these four scales also demonstrated low to moderate correlations (.33 to .58). CONCLUSIONS: The two modes of administration may not produce interchangeable results. Researchers should be cautious when mixing modes of administration to elderly patients. PMID- 7983298 TI - Geriatric home assessment after hospital discharge. PMID- 7983299 TI - Risks of long-term urethral catheterization. PMID- 7983301 TI - The status of geriatric medicine. PMID- 7983300 TI - Altered cognitive functions in a population of elderly people hospitalized for fall-related fractures. PMID- 7983302 TI - Fatal primary hyperparathyroidism with myopathy involving respiratory muscles in an old woman. PMID- 7983303 TI - Tetanus in a 74-year-old woman. PMID- 7983304 TI - Metoclopramide-induced extra pyramidal symptoms in a diabetic patient. PMID- 7983306 TI - [Complications of cordocentesis]. PMID- 7983305 TI - [Complications from chorionic villus sampling and amniocentesis]. PMID- 7983307 TI - [Limits of detection, undesirable side-effects, and impact on labor outcome of the use of fetal electronic monitoring and tocography]. PMID- 7983309 TI - [Complications of diagnostic laparoscopy]. PMID- 7983308 TI - [Complications of hysterosalpingography]. PMID- 7983310 TI - [Complications of echoguided gynecological biopsies]. PMID- 7983312 TI - [Complications of echo- or radioguided breast biopsies]. PMID- 7983311 TI - [Complications of hysteroscopy]. PMID- 7983313 TI - [Medical and legal complications]. PMID- 7983314 TI - [Medical and legal implications of exploratory gynecological endoscopies in Belgium]. PMID- 7983315 TI - [Diagnostic hysteroscopy and medical-legal implications]. PMID- 7983316 TI - [The practice of ultrasonography in gynecology-obstetrics: standard performance and results]. PMID- 7983317 TI - [The obstetrician's responsibility as a member of a multidisciplinary prenatal diagnosis team]. PMID- 7983318 TI - [Medical-legal aspects related to use and diffusion of complementary exploratory imaging in gynecology-obstetrics]. PMID- 7983319 TI - [Growth factors and cancer]. PMID- 7983320 TI - [Alternatives to hospitalization in gynecology-obstetrics]. PMID- 7983321 TI - [Our experience and evaluation trial of obstetrical telemonitoring]. PMID- 7983323 TI - [The different surveillance modalities in high risk pregnancies]. PMID- 7983322 TI - [Home care services in gynecology-obstetrics: administrative and economic problems]. PMID- 7983324 TI - [The day hospital in gynecology-obstetrics]. PMID- 7983326 TI - [Home care services and postnatal care. The experience in Grenoble (1985-1993)]. PMID- 7983325 TI - [Fetal telemonitoring]. PMID- 7983327 TI - [Uterine malformations and pregnancy]. PMID- 7983328 TI - [In utero exposure to diethylstilbestrol and pregnancy]. PMID- 7983329 TI - [Endoscopic treatment of the septate uterus]. PMID- 7983330 TI - [Echoguided resection of the septate uterus]. PMID- 7983331 TI - [Longitudinal septate vaginas and pregnancies]. PMID- 7983332 TI - [Vaginal aplasia and functional uterus]. PMID- 7983333 TI - [Bladder exstrophy and pregnancy]. PMID- 7983334 TI - Social support and social structure: a descriptive epidemiology. AB - Despite a very large and growing literature demonstrating the significance of social support for health and well-being, surprisingly little is known about the social distribution of this crucial resource. This paper presents data on the distribution of social support and support resources across social class, marital status, age and gender, with the aims of contributing toward an understanding of the impact of social structures on processes of social support, and of assessing the hypothesis that epidemiological variations in mental health arise partially from social support differences. The epidemiology of perceived social support was found to correspond closely to the epidemiology of psychological distress and disorder. The single exception involved gender, where a positive rather than negative relationship was observed, with women demonstrating the highest levels of both social support and psychological distress. The observed patterns of variation in social support link this significant adaptive resource to one's locations in the social structure and reinforce the conclusion that it represents a promising intervention target. The practical importance of these results, however, are not matched by theoretical significance. Except in the case of marital status, our findings largely discount the hypothesis that the social distribution of mental health is partially attributable to social support differences. PMID- 7983335 TI - The social stratification of aging and health. AB - The way health varies with age is importantly stratified by socioeconomic status (SES)--specifically, education and income. Prior theory and cross-sectional data suggest that among higher SES persons the onset of health problems is usually postponed until rather late in life, while health declines are prevalent in lower SES groups by middle age. Thus, SES differences in health are small in early adulthood, but increase with age until relatively late in life, when they diminish due to selection or greater equalization of health risks and protections. The present paper strengthens our causal and interpretive understanding of these phenomena by showing: (1) that results previously reported for indices of SES hold separately for education and income; (2) that the interaction between age and SES (i.e., education or income) in predicting health can be substantially explained by the greater exposure of lower SES persons to a wide range of psychosocial risk factors to health, especially in middle and early old age, and, to a lesser degree, the greater impact of these risk factors on health with age; and (3) that results (1) and (2) generally hold in short-term longitudinal as well as in cross-sectional data. Implications for science and policy in the areas of aging, health, and social stratification are discussed. PMID- 7983336 TI - Women, work, and well-being: the importance of work conditions. AB - This study investigates the role of work conditions in mediating the effect of employment status on married women's psychological well-being. Employed wives and full-time homemakers are compared on characteristics of their daily work activities and the consequences of these work conditions for psychological well being. Using data from a national survey of employed wives and homemakers, I find that full-time housework involves more autonomy, more interruptions, greater physical effort, more routine, fewer time pressures, and less responsibility for matters outside one's control than paid work. Differences in work activities between employed wives and homemakers also have direct implications for well being. Two of the dimensions examined--the extent to which the worker is responsible for things outside her control, and the amount of routine entailed- are associated with greater depressive symptoms among women, regardless of work status. It appears that, as compared to employed wives, full-time homemakers benefit from having less responsibility for things outside their control. Employed wives appear to benefit from having less routinized work than homemakers. As a result of the different configurations of their work characteristics, employed wives and homemakers experience on average similar levels of depressive symptoms. PMID- 7983338 TI - The macroeconomic context of job stress. AB - Using data from the 1973-1977 Quality of Employment Panel Study, we test a model that conceptually links research on macroeconomic causes of stress with research on job structure causes of stress among employed workers. Results from LISREL 7 (Joreskog and Sorbom 1989) indicate that, while both macroeconomic and job structure variables have significant cross-sectional and longitudinal effects on stress, the macroeconomic effects are almost entirely indirect in their effect on job structures. In particular, higher occupational unemployment rates increased stress and lowered life satisfaction indirectly through reduced decision latitude and increased job demands. Overall, results suggest that macroeconomic changes, such as recessions, can affect individual stress because they lead to changes in routine job structures that represent increased and continued exposure to stressful conditions. PMID- 7983337 TI - Differential influence of parental smoking and friends' smoking on adolescent initiation and escalation of smoking. AB - Smoking-related behaviors and attitudes of significant others (especially friends and parents) are among the most consistent predictors of adolescent smoking. However, theorists remain divided on whether the behaviors of significant others influence adolescent smoking directly or indirectly, and the relative influence of parental and peer smoking on adolescents' own smoking is still a matter of debate. In addition, little research has examined the role of significant others' behavior on different stages of smoking onset. In particular, not much information is available regarding gender and ethnic differences in social influences on smoking behavior. We use structural equation modeling to address these issues. Different theoretical perspectives from cognitive-affective theories (Ajzen 1985; Ajzen and Fishbein 1980) and social learning theories (Akers et al. 1979; Bandura 1969, 1982, 1986) have been integrated into a structural model of smoking influence. The results show that friends' smoking affects adolescent initiation into smoking both directly and indirectly, whereas parental smoking influences smoking initiation only indirectly. The data also show that friends' and parents' smoking affect smoking escalation only indirectly. In general, friends' smoking has a stronger effect on adolescents' smoking behavior, particularly on initiation. Multiple group comparisons of the structural models predicting smoking initiation among males and females reveal that parental approval of smoking plays a significant mediating role for females, but not for males. Comparisons of Whites, Blacks, Hispanics, and other ethnic groups reveal that there are some significant differences in the pathways of friends' influences among the four groups. PMID- 7983339 TI - The interpersonal context of mental health interviews. AB - Little is known about the composition and effects of the interpersonal contexts in which epidemiological interviews are conducted. The Epidemiological Catchment Area (ECA) study affords an opportunity to examine the frequency and impact of third party presence. Almost half of the interviews at the Los Angeles site of the ECA study were conducted in the presence of a third part, typically the spouse or child of the respondent. Results indicate that third party presence is not related either to reports of symptoms or to performance on a test of cognitive impairment. Although findings suggest that respondents are not influenced by the presence of others, they may also reflect a variety of cultural, situational, and methodological processes. PMID- 7983340 TI - Pitfalls in infection control. PMID- 7983341 TI - (0)-(0) = 0. PMID- 7983342 TI - Hospital tuberculosis: beyond the inner city. PMID- 7983343 TI - Changing patterns of mycobacterial disease at a teaching community hospital. AB - OBJECTIVES: To evaluate trends in the occurrence and diagnosis of mycobacterial disease. DESIGN: Prospective surveillance study using a central tuberculosis registry at a 611-bed teaching community hospital. RESULTS: Data pertaining to 715 patients were entered into the registry between 1976 and 1991 on the basis of positive smears or cultures for acid-fast bacilli (AFB). Over time, the ratio of isolates of Mycobacterium tuberculosis to isolates of nontuberculous mycobacteria reversed (from 3.2 to 1 between 1976 and 1981 to 1 to 1.6 between 1986 and 1991). The sensitivity of the sputum AFB smear for diagnosis of pulmonary tuberculosis increased (from 0.73 to 0.96), but the positive predictive value of the sputum AFB smear declined (from 0.72 to 0.59). The acquired immunodeficiency syndrome epidemic accounted for these changes only to a small extent. CONCLUSIONS: The increasing occurrence of non-tuberculous mycobacterial disease and the declining positive predictive value of the sputum AFB smear at this hospital imply that respiratory isolation and antituberculous therapy will be used inappropriately for many patients. The development and use of newer tests for early isolation and specific identification of M tuberculosis should be accelerated. PMID- 7983344 TI - Real and apparent tuberculin skin test conversions in a group of medical students. AB - OBJECTIVE: To evaluate tuberculin skin test (TST) conversions among a group of medical students. DESIGN: Questionnaire sent to a medical school class in whom a cluster of TST conversions was noted, and interview and repeat TST of students with conversion. SETTING: County hospital and associated medical school. SUBJECTS: Medical students, after their third year in medical school. RESULTS: Of 165 students in the class, 115 (70%) responded; 10 reported TST conversions between the beginning of the third and the fourth year. Seven of 10 were interviewed, and all 10 were retested. Five students, all in a cohort who tested each other during a clinical clerkship with a tuberculin material previously reported to be associated with a high rate of false-positive TSTs, were TST negative on repeat. Five had persistently positive TSTs. One was exposed during a psychiatry clerkship to a resident with pulmonary tuberculosis. Four students appeared to have converted their TST during their third year in medical school. All four did their medicine clerkship at a large county hospital (P < 0.02; odds ratio = 16.4) that had few infection control measures in place for tuberculosis isolation during the time of their exposure. CONCLUSIONS: We recommend that medical students, as well as other healthcare professions students, be educated about infection control practices and skin tested at least annually during clinical training years. PMID- 7983345 TI - Plasmid DNA profiles of Acinetobacter baumannii: clinical application in a complex endemic setting. AB - OBJECTIVE: To study the epidemiological, microbiological, and clinical features of infections due to Acinetobacter baumannii in a complex endemic situation over an 18-month period and to determine the clinical usefulness of plasmid DNA analysis of A baumannii in epidemiological investigations. DESIGN: Review of medical and laboratory records. Antibiotic resistance patterns, biotyping, and plasmid profile analysis were used to characterize clinical and environmental isolates. Pulsed-field gel electrophoresis (PFGE) of chromosomal DNA was performed to verify results obtained with the other typing methods. SETTING: Four different intensive care units of an 800-bed tertiary care center in Cologne, Germany. RESULTS: 240 patients were colonized or infected with A baumannii during the study period. No seasonal variations were observed. The majority of isolates (53%) were recovered from the respiratory tract. Major infections occurred in 61 patients; these included 48 bacteremias and eight pulmonary infections. Five different epidemic strains were identified: one each was A baumannii biotype 2 and 6, and three were biotype 9. A baumannii biotype 9 accounted for the vast majority of isolates (88%), which were clustered into three epidemic strains demonstrating distinct plasmid profiles. Two of these were considered genetically related as shown by PFGE. Epidemic strains were multidrug resistant, being uniformly susceptible to imipenem only. An epidemiological investigation failed to identify any point source of infection. Barrier precautions and improved handwashing was instituted in three of the four units and significantly reduced the incidence of colonization and infection in these units. Attack rates remained unchanged, however, in the burns unit where control measures were not implemented. CONCLUSION: Acinetobacter strains representing multiple biotypes and plasmid types were present in this endemic setting. Multidrug resistance in A baumannii is an important concern. Plasmid DNA analysis proved to be useful in epidemiological typing of A baumannii strains and may serve as a complementary typing system to traditional epidemiological methods. PMID- 7983346 TI - Nosocomial legionellosis associated with aspiration of nasogastric feedings diluted in tap water. AB - PROBLEM: Two cases of nosocomial legionellosis due to Legionella pneumophila serogroup 6 (Lp6) were identified in the intensive care unit. Both patients had a history of aspiration of nasogastric tube feedings, developed pulmonary infiltrates, had positive cultures for Lp6, had serological titer rises to Legionella, were treated, and recovered. METHOD: Isolates of Lp6 from the potable water system and patients were characterized by DNA restriction enzyme analyses using pulsed-field gel electrophoresis (PFGE). RESULTS: Water samples grew > 10(4) CFU/L of Lp6, and the same PFGE pattern was observed with the patient and water isolates. Potable water was used only for delivering medications and diluting feeding solutions given through the nasogastric tubes of the patients. Heat shock of the hot water system (140 degrees to 160 degrees F or 60 degrees to 70 degrees C, 4 hours) was performed and the temperature was maintained between 131 degrees to 140 degrees F (55 degrees to 60 degrees C). Surveillance over 18 months revealed a reduction in Legionella to < 10(2) CFU/L. CONCLUSION: We speculate that nosocomial Legionella pneumonia occurred due to aspiration of nasogastric tube solutions diluted with tap water. A nursing practice change to use only sterile water to dilute feedings and flush medications for nasogastric administration was instituted. The hot water temperature at the faucet was increased to > or = 131 degrees F (> or = 60 degrees C) to control Legionella. No further nosocomial cases have occurred. PMID- 7983347 TI - A common source outbreak of gastroenteritis in a teaching hospital. AB - An outbreak of gastroenteritis at a large teaching hospital affected at least 52 workers. Investigation implicated a tuna salad, and the circumstances suggested Clostridium perfringens as the etiologic agent. The risk of such outbreaks may be reduced by cooling of ingredients prior to mixing and refrigeration in small steel containers. PMID- 7983348 TI - Utility of the hospital tuberculosis registry. AB - Emerging guidelines suggest that the management of tuberculosis and suspected tuberculosis in the hospital will become an increasingly costly enterprise. The local hospital registry can be a focal point for determining the extent to which such measures are necessary at individual institutions, that existing infection control recommendations are being carried out, and that patients released from the hospital are not lost to follow-up. Consideration might be given to inclusion of all patients begun on antituberculous therapy, regardless of the results of acid-fast bacilli cultures, in view of renewed concern about patient compliance. PMID- 7983350 TI - Bootstrapping. PMID- 7983349 TI - Scabies epidemic: price and prejudice. AB - Scabies epidemics are not unusual, and the recommended way of stopping them is by simultaneous treatment of everybody in the facility; this has been known since the last century, when Norwegian scabies was a problem in Norway. When this is not done, scabies epidemics can smolder for months. Scabies should not spread with good infection control measures, but we learned that a good infection control service is not enough. Efforts have to be done to educate everybody in the hospital, including laundry workers, and to improve work conditions. PMID- 7983351 TI - The use of molecular typing techniques in the epidemiologic investigation of resistant enterococci. PMID- 7983352 TI - Catheter-associated bacteriuria in long-term care facilities. AB - Catheter-associated bacteriuria is the most common infection acquired in long term care facilities. Complications include fever, acute pyelonephritis, bacteremia, catheter obstruction, urinary stones, chronic interstitial nephritis, renal failure, and death. The closed-catheter system has been the only innovation in this traditional method of care that has led to prevention of bacteriuria. Antimicrobial agents rarely are indicated to prevent or treat bacteriuria in long term catheterized patients, except for those with symptomatic infection. Alternative devices are available and often may be preferable to the indwelling urethral catheter. These patients and their reservoirs of bacteriuric organisms are sources of nosocomial outbreaks. Such outbreaks can be prevented and controlled with attention to catheter hygiene, prevention of patient-to-patient transmission on the hands of caregivers, and possibly use of antimicrobials to diminish bacterial concentrations in the urine. PMID- 7983353 TI - In situ localization and chromosomal mapping of the AG1 (Dmp1) gene. AB - Dentinogenesis is being used as a model for understanding the biomineralization process. The odontoblasts synthesize a structural matrix comprised of Type I collagen fibrils which define the basic architecture of the tissue. The odontoblasts also synthesize and deliver a number of dentin-specific acidic macromolecules into the extracellular compartment. These acidic macromolecules may be involved in regulating the ordered deposition of hydroxyapatite crystals within the matrix. AG1 is the first tooth-specific acidic macromolecule to have been cloned and sequenced. To identify which cells of the rat incisor pulp/odontoblast complex were responsible for synthesis of AG1, in situ hybridization was used. Digoxigenin labeled sense and anti-sense AG1 riboprobes were prepared. The AG1 mRNA was found to be expressed in the mature secretory odontoblasts. Neither pulp cells nor pre-odontoblasts showed any staining with the anti-sense probes. Chromosomal localization studies placed the AG1 gene on mouse chromosome 5q21, in tight linkage with Fgf5. AG1 has been renamed Dmp1 (dentin matrix protein 1) in accordance with present chromosomal nomenclature. Mouse 5q21 corresponds to the 4q21 locus in humans. This is the locus for the human tooth mineralization disorder dentinogenesis imperfecta Type II (DI-II). These data suggest that the Dmp1 gene is involved in mineralization and is a candidate gene for DI-II. PMID- 7983354 TI - Novel in situ double labeling for simultaneous detection of proliferation and apoptosis. AB - We describe a novel double-labeling method to simultaneously investigate proliferation and apoptosis from plastic-embedded biopsy specimens (PEBs). Infusions of bromo- and/or iododeoxyuridine (BrdU/IudR) were given to 10 patients, five with acute myeloid leukemia (AML) and five with myelodysplastic syndromes (MDS), and S-phase cells were measured in PEBs using a monoclonal anti IudR/BrdU antibody. Apoptosis was measured by in situ end-labeling (ISEL) of DNA. The results demonstrate that both AML and MDS are highly proliferative disorders but that there is almost no apoptosis in the former, whereas extensive apoptosis was observed in the latter. Double labeling revealed that large numbers of S phase cells in MDS were simultaneously undergoing apoptosis. We conclude that the high cell death in MDS cancels the high cell birth, resulting in a functionally aplastic marrow and thus accounting for the observed ineffective hematopoiesis. On the other hand, AML is rapidly fatal, probably owing to high cell birth with no or minimal cell death. Therapeutic strategies to prevent intramedullary programmed cell death of hematopoietic precursors should be evaluated in MDS, and efficacy of chemotherapy in AML can be assessed by measuring the induction of apoptosis in post-treatment biopsy specimens. PMID- 7983356 TI - Microwave-stimulated antigen retrieval is pH and temperature dependent. AB - The effects of the pH of solutions used in microwave-stimulated antigen retrieval were investigated for two antibodies commonly used in neurosciences, MAP-2 and SMI-32. A prolonged fixation time (longer than 1 week) prevents good immunohistochemical staining of these and many other antigens in paraffin and vibratome sections. On human brain tissue stored for 17 months in formaldehyde, the effects of different solutions during microwave treatment were compared, i.e., 4% aluminum chloride (pH 2.75), 0.1 N hydrochloric acid (pH 0.98), and citrate buffers (pH 2.5, 4.5, 6.0), together with the influence of temperature and microwave irradiation. We conclude that the pH and temperature of the solutions and the irradiation time are of great importance for the retrieval of antigens, but in a different way for the two antibodies studied. The SMI-32 staining results are optimal with citrate buffer at pH 2.5 and 2-hr irradiation at 90 degrees C, whereas MAP-2 staining results are optimal with citrate buffer at pH 4.5 and 10-min full-power irradiation. In the other conditions the staining is less intensive or less homogeneously distributed over the section. PMID- 7983355 TI - Filipin vs enzymatic localization of cholesterol in guinea pig, mink, and mallard duck testicular cells. AB - To test the validity of filipin cytochemistry for localization of cholesterol in testicular cells, we compared the results obtained by this technique with those obtained by a two-step enzymatic method involving cholesterol esterase and cholesterol oxidase. In all the animals models tested (guinea pig, mink, and mallard duck) the disappearance of subsurface filaments along Sertoli cell junctional membranes was accompanied by a significant increase in the number of filipin-cholesterol complexes/microns 2 in these membranes. Enzyme histochemistry allowed localization of free cholesterol in the limiting membrane of multivesicular bodies, in membranes within lysosomes, in mitochondrial membranes, and in junctional membranes, with or without subsurface filaments. The method also permitted selective visualization of cholesterol esters in lipid droplets. We conclude that filipin mapping of cholesterol induces false-negative cytochemical results. The enzymatic method is superior to filipin because it allows localization of free cholesterol in junctional membranes and of cholesterol esters in lipid droplets. This compartmentalization of the compounds may represent the basis of a system that helps to maintain constant free cholesterol levels in the testis. PMID- 7983357 TI - Quantitation of P450 aromatase immunoreactivity in human ovary during the menstrual cycle: relationship between the enzyme activity and immunointensity. AB - To understand changes associated with the menstrual cycle in the human ovary, it is very important to examine chronological changes in P450 aromatase (P450arom) enzymatic activity in the normal cycling ovary. Therefore, we initially examined the correlation between intensity of P450arom immunoreactivity and its biochemical enzymatic activity in five estrogen-producing human cancer cell lines (HHUA, Ishikawa, HEC-59, OMC-2, and MCF-7). P450arom immunointensity per cell was evaluated by the CAS 200 computed image analysis system, and its catalytic activity per 10(6) culture cells was analyzed by the tritiated water method. A significant correlation (r = 0.959) was demonstrated between P450arom immunoreactivity and enzymatic activity under optimal conditions of tissue fixation and immunohistochemical procedures. We then investigated P450arom immunointensity in 31 specimens of normal cycling human ovaries to examine chronological changes in P450arom activity per cell throughout the menstrual cycle. In the follicular phase, P450arom was observed in the granulosa cells of one selected antral follicle per case during the mid- to late proliferative period, and its immunointensity per granulosa cell in the follicle was not significantly different between mid- and late proliferative periods, although serum estradiol level was markedly elevated in the late proliferative period. In the luteal phase, both P450arom immunointensity per luteinized granulosa cell in a corpus luteum and serum estradiol level reached a peak in the mid-secretory period. These findings indicate that different factors may influence ovarian P450arom activity during the follicular and luteal phases, i.e., an increased number of granulosa cells in the selected follicle during the follicular phase but changes in P450arom activity per luteinized granulosa cell in the corpus luteum during the luteal phase. PMID- 7983358 TI - Localization of copper to afferent terminals in rat locus ceruleus, in contrast to mitochondrial copper in cerebellum. AB - We examined copper localization in the locus ceruleus and cerebellum of rat brain by Timm's sulfide-silver staining, as modified by Danscher. Dense silver particles revealing copper localization were observed in sections of the locus ceruleus and cerebellum after pre-treatment with trichloroacetic acid. In the locus ceruleus, copper appeared to be distributed to neuropil rather than glial or neuronal cell bodies, and at the ultrastructural level copper was mainly localized on synaptic membranes of afferent terminals in contact with somatic spines or dendrites of locus ceruleus neurons, whereas copper was distributed to mitochondria in the granular layers of cerebellum and fine, sparse silver particles were observed throughout ependymal cells and epithelial cells of blood vessels. The specific localization of copper to afferent terminals in the locus ceruleus was confirmed by X-ray microanalysis, which showed a significant level of copper, but not zinc, in synaptic membranes. These results suggest a distinct role of copper depending on its regional distribution. Copper or copper protein may be involved in neurotransmission in the locus ceruleus but in mitochondrial activity in the cerebellum. PMID- 7983359 TI - Altered collagen expression in human dentin: increased reactivity of type III and presence of type VI in dentinogenesis imperfecta, as revealed by immunoelectron microscopy. AB - We used transmission immunoelectron microscopy and polyclonal antibodies to study the reactivities of Types III and VI collagen in dentin of normal human permanent and primary teeth and in primary teeth from five patients with dentinogenesis imperfecta (DI) associated with osteogenesis imperfecta and occurring as a single trait. In the normal permanent tooth, reactivity of Type III collagen was occasional and, where present, peritubular. Staining of normal primary teeth was less occasional but still rare, whereas the abnormal dentin stained more uniformly. Atypical, non-striated fibrillar structures that also showed Type III collagen reactivity were observed in dentin of two of the three patients with DI as a single trait. Later, these two patients proved to be first cousins. Unlike antibodies to the N-terminal pro-peptide of Type I pro-collagen, antibodies to the C-terminal telopeptide of Type I collagen, used for comparison stained the affected dentin homogeneously. Reactivity of Type VI collagen, not detected in normal teeth, was seen in the dentin of all abnormal teeth, in association with non-fibrillar delicate material. This study also shows that although readily detectable in dentin affected by DI, Type III collagen is a minor constituent of normal human dentin matrix. PMID- 7983360 TI - Liver regeneration: a comparison of in situ hybridization for histone mRNA with bromodeoxyuridine labeling for the detection of S-phase cells. AB - We developed an in situ hybridization technique for measurement of proliferative cell numbers through detection of histone mRNA in routinely fixed, paraffin embedded tissue sections. Histone gene expression is coordinated with the cell cycle, and the increase in expression during S-phase permits unambiguous identification of cells undergoing DNA replication. Histone mRNAs were identified in routinely processed rat liver tissue by non-isotopic in situ hybridization with digoxigenin-labeled oligonucleotide probes. Specific hybrids were detected with alkaline phosphatase-labeled anti-digoxigenin antibody and visualized by BCIP-nitroblue tetrazolium indicator substrate. Unequivocal cytoplasmic labeling was observed in various cell types in the liver remnant during the first 72 hr after a two-thirds partial hepatectomy. The spatial and temporal patterns of histone labeling were almost identical to those obtained by staining with an antibody to bromodeoxyuridine. The identification of histone mRNA appears to be a reliable marker of the S-phase fraction, a technique with the further advantage that the tissue does not have to be first exposed to a nucleotide analogue. Hence, retrospective studies are possible. The probes can be applied to human and animal cells and tissues because the nucleotide sequences of histone genes are conserved. PMID- 7983361 TI - Localization of sugar-binding sites in Staphylococcus aureus using gold-labeled neoglycoprotein. AB - We studied post- and pre-embedding staining of sugar-binding sites on thin sections of Staphylococcus aureus with an electron microscopic neoglycoprotein gold technique. Although gold particles of cellobiosyl bovine serum albumin (BSA) glycosylated BSA-, lactosyl BSA-, and melibiosyl BSA-gold did not label, heavy labeling of N-acetylglucosaminide-BSA-gold was observed in both the cell wall and the cytoplasm on Spurr-embedded thin sections of S. aureus. Inhibition of labeling with wheat germ agglutinin-biotin and N-acetylglucosaminidase indicated that the labeling was due to N-acetylglucosamine. These data suggested that molecules that bind specifically with N-acetylglucosamine occur in the cell wall and cytoplasm of S. aureus. Pre-embedding staining revealed that these molecules are abundant at the surface of the cell wall and that the abundance differs depending on the bacterial strain. An N-acetylglucosamine-specific lectin-like substance, glucosaminidase, and toxins are proposed as candidates for molecules responsible for the labeling, and the possible functional significance of the findings is discussed briefly. PMID- 7983362 TI - Use of 1.4-nm immunogold particles for immunocytochemistry on ultra-thin cryosections. AB - We present a new application for the use of small immunogold particles (approximately 1.4-nm diameter) for ultrastructural immunocytochemistry. These small gold particles have been used on ultra-thin cryosections in conjunction with a silver enhancement procedure that does not degrade ultrastructural detail. We have used the human neutrophil as a model system, in which known protein markers of two different cytoplasmic granules were localized, in the development of this procedure. The 1.4-nm immunogold particles coupled with silver enhancement yield intense labeling for localization of lactoferrin, a marker for the specific granules, and myeloperoxidase, a marker for the azurophil granules. Double labeling in which one antigen was visualized with 1.4-nm gold and silver enhancement and a second antigen was detected with colloidal gold-IgG on the same ultra-thin cryosection was successfully achieved. We also show that 1.4-nm diameter immunogold particles penetrate into cryosectioned neutrophils to a greater extent than 5-nm or 10-nm immunogold probes. These results show that small immunogold particles, along with silver enhancement, are a useful addition to the immunolabeling methods available for use with ultra-thin cryosections. PMID- 7983363 TI - Diagnostic utility of quantitating neurofilament-immunoreactive Alzheimer's disease lesions. AB - The diagnosis of Alzheimer's disease (AD) neurodegeneration is based on histopathological detection of paired helical filament-associated lesions. Silver stains are routinely used but the results are fraught with intra- and interinstitutional variability. This study employed monoclonal antibodies to middle and high molecular weight neurofilament subunits in an immunohistochemical assay to assess the extent of paired helical filament-associated lesions in brains with AD, Down's syndrome plus AD lesions (AD+DN), Parkinson's disease dementia (PD), AD+PD, and normal aging changes. The densities of neurofilament immunoreactive (NFI) cortical neurofibrillary tangles and plaques were significantly higher in AD and AD+DN than in PD and aged control brains (p < 0.001), and NFI neurofibrillary tangles and plaques were more abundant in AD and AD+DN compared with AD+PD and PD, yet all patients with AD, AD+PD, or PD died with end-stage dementia. In contrast, the densities of NFI dystrophic neurites (primarily dendrites) in cortical Layer 2 were similar among the AD, AD+DN, AD+PD, and PD groups, and all were significantly higher than control (p < 0.005). Stepwise multivariate regression analysis demonstrated significant correlations between AD diagnosis and high densities of NFI neurofibrillary tangles and plaques (p < 0.001) and between end-stage AD-type dementia and high densities of NFI dystrophic neurites (p < 0.001). This study demonstrates that the histopathological lesions correlated with AD dementia can be readily detected and quantified by immunostaining with monoclonal antibodies to phosphorylated and non phosphorylated neurofilaments. Moreover, the findings suggest that NFI neurite pathology may be an important feature contributing to the clinically manifested AD-type dementia in individuals with Parkinson's disease. PMID- 7983364 TI - cFos immunoreactivity is enhanced with biotin amplification. AB - Through modification of the protocol by Adams, we developed a biotin amplification procedure for immunofluorescence staining of immediate early gene proteins and also applied biotin amplification for metal enhancement of diaminobenzidine staining in an immunoperoxidase protocol. Commercially available anti-cFos antisera were used to compare conventional "Elite" avidin-biotin complex reactions with biotin amplification reactions (visualized with peroxidase staining or streptavidin-Texas Red fluorescence). Biotin amplification and peroxidase staining (with or without nickel salts) enabled detection of cFos in stimulated neurons with primary antibody concentrations five- to tenfold lower than the conventional procedure. With immunofluorescence staining, at primary antibody concentrations too low to detect cFos with the conventional biotin streptavidin fluorescence staining protocol, biotin amplification enabled clear cFos fluorescence staining with both antisera. The fluorescence staining exhibited a high signal-to-noise ratio and enabled antibody concentrations four times lower than those used for conventional ABC "Elite" peroxidase procedures. In conclusion, the application of biotin amplification to cFos immunocytochemical localization has the promise of aiding the scientist in detecting these immediate early gene products. PMID- 7983365 TI - An alternative method for preparation of Schiff-like reagent from osmium-ammine complex for selective staining of DNA on thin Lowicryl sections. AB - Batches of osmium-ammine (OA) complex vary considerably in staining properties when used in a Feulgen-like reaction for selective staining of DNA-containing structures. An alternative procedure for preparation of Schiff-like reagent from OA complex is described. It is based on generation of H2SO3, respectively SO2, within the OA solution and ensures more favorable conditions for production of a Schiff-like stain than bubbling with SO2 does. The method is reproducible and yields high staining intensity. Data obtained suggest that the ability of OA complex to produce Feulgen-like staining is strongly influenced by variations in its chemical composition. Their unfavorable effect can be overcome by selecting suitable conditions for preparation of a Schiff-like reagent. Conditions for obtaining specific and sensitive Feulgen-like staining are determined. PMID- 7983366 TI - Pseudocolor image processing of PEPCK subcellular distribution in rat hepatocytes shown with IGSS and epipolarization microscopy. PMID- 7983367 TI - Serotoninergic supraependymal plexus in the ventricular system of the hedgehog: organization principles and functional implications. AB - The distribution of serotonin (5-HT) immunoreactive fibers in the ventricular system of the hedgehog Erinaceus europaeus was studied by means of specific antibodies against serotonin. Light microscopic examination of immunocytochemically stained coronal sections showed abundant serotoninergic fibers, unevenly distributed along the ventricular wall, both supraependymally and subependymally. No immunoreactivity was evident in the choroid plexus. Serotonin fibers lying supraependymally exhibited distinct morphological and distributional features. They were either found to terminate freely in the ventricular lumen or contributed to the formation of a large number of interconnected basket-like formations, particularly abundant in the lateral and fourth ventricles, where they usually lay opposite to the choroid plexus. In the electron microscopic study of the 5-HT-stained thin sections, the ependymal monolayer was found to be composed of squamous or cuboidal cells protruding into the ventricle. Immunoreactive axons cut in favorable tangential planes formed typical baskets that encircled the apical cytoplasmic process of the ependymal cells. Immunoreactive varicosities containing clear and dense cored vesicles were found either to terminate as "free arborizations" within the ventricles, or contacted the ventricular surface of ependymal cells. In these contacts, junctional specializations resembling those of classical synapses were often observed. The functional significance of the 5-HT baskets which surround individual ependymal cells is briefly discussed. PMID- 7983368 TI - Volumetric comparison of hippocampal regions in 44 primate species. AB - Volumes of retrocommissural hippocampal regions (Subiculum, CA 1, CA 2, CA 3, hilus region, and fascia dentata) were measured using serial sections of 44 species of prosimian and simian brains, including man. The volumes were compared allometrically with those of the least encephalized eutherian mammals, the madagassian tenrecs (Insectivora, Tenrecinae; 4 species). The retrocommissural hippocampus is 2.9 times larger in prosimians, 2.4 times in non-human simians, and 4.1 times in man. The different hippocampal regions do not enlarge uniformly to the same degree as the total hippocampus. The regions can be grouped into three categories, according to the degrees to which they enlarge in primates: a) Structures with the greatest degree of enlargement are the subiculum and the field CA 1. b) An enlargement similar to that of the total retrocommissural hippocampus is seen for the hilus region. c) No or only a slight enlargement as compared to their sizes in tenrecs is observed for the hippocampal fields CA 2, CA 3, and the fascia dentata. PMID- 7983369 TI - Primary trigeminal afferent neuron of the cat: I. Studies on membrane-bound enzyme histochemistry. AB - The localization of some membrane-associated enzymes such as alkaline phosphatase, 5'-nucleotidase, glucose-6-phosphatase, Na+,K(+)-adenosine triphosphatase, adenylate cyclase and guanylate cyclase in the Merkel cell-axon complexes, trigeminal ganglia and the principal trigeminal sensory nucleus of the cat was determined at light and electron microscopic level using cytochemical techniques. In the sinus hair follicles (vibrissae), the reaction end product marking alkaline phosphatase and adenosine triphosphatase activities was visualized on the axons running through external follicle epithelium and the 5' nucleotidase, adenylate- and guanylate cyclase positive reaction was seen to stain the plasma membranes of Merkel cells. In the trigeminal ganglia, the strongest alkaline phosphatase and adenosine triphosphatase activities showed the corresponding areas between the ganglion and satellite cells. 5'-nucleotidase activity was more intense on the neurilemmas and the surrounding glial plasma membranes. In the principle sensory trigeminal nucleus, the central neurons exhibited an intense alkaline phosphatase, 5'-nucleotidase and adenosine triphosphatase activities and much smaller amount of reaction product for adenylate cyclase and guanylate cyclase was observed. In conclusion, membrane bound enzymes could be histo- and cytochemically demonstrated in all components of primary trigeminal afferent units. Our results have confirmed that the receptor function and the nerve impulses conductance need an intensive molecular and cation exchange, and energy supply. PMID- 7983370 TI - A set of early-born neurons is distinctly labeled by several defined antibodies in the adult rabbit retina. AB - Retinal ganglion cells, cone photoreceptor cells, and horizontal cells arise earlier in ontogenesis than the other retinal cell types. Although during the first postnatal week of life much cell proliferation occurs in the rabbit retina, 3H-thymidine labeling shows that these particular neurons are already postmitotic in neonatal animals. We show here that, in the adult retina, these early-born neurons express antigens as neuron-specific enolase, HNK-1 epitope of N-CAM, and PGP 9.5 antigen, which are not expressed by the neurons later born. It is concluded that the mammalian retina contains two genotypically different sets of neuronal cells which can be distinguished by immunocytochemistry. PMID- 7983371 TI - Aberrant visual pathways in microphthalmic mice. AB - We report results obtained in the microphthalmic strain of mice 944. Heterozygotes appear normal, but they produce litters in which typically between 2 and 5 offspring exhibit microphthalmia. As a result these animals are blind. Our investigations using the fluorescent tracer DiI show that in microphthalmic mice there is a small compensation for the missing retinal input by terminals or axon collaterals originating in the somatosensory thalamus. These morphological findings agree with somatosensory responses recorded in the visual cortex (EEG recordings). PMID- 7983372 TI - Ultrastructure of lamellar granules coating glial cell basal lamina in the olfactory bulb and olfactory subtracts of goldfish. AB - Lamellar granules, 35 to 80 nm in diameter, are observed in the pia-arachnoid tissue of regenerated olfactory bulb and olfactory subtracts of the goldfish. The granules correspond to multiple stacks of disks which cover basal lamina of both pial and ependymal cell layers and blood vessels. The granules are also in close association with collagen fibril bundles. The granules are observed only in young goldfish or after bilateral olfactory tract transection in 1 year postoperated animals. Our findings suggest that these granules are secreted by connective tissue cells in response to damage associated with bilateral olfactory tract transection. Coexisting extracellular free granules and the granules covering basal lamina are simultaneously found in regenerated olfactory bulb and olfactory tract. Many of our findings, as far as we know, have not been described previously. The composition and function of these granules are at present unknown. PMID- 7983373 TI - Organization of the motor innervation of craniocervical muscles in the Mallard, Anas platyrhynchos L. AB - The organization of the motorsystem supplying the craniocervical muscles in the mallard was investigated. Firstly, the distribution of peripheral nerves supplying these muscles was macroscopically examined. Each muscle was found to be innervated by several spinal nerves, and each nerve to contact various muscles. Secondly, the position of neck motoneurons was studied by means of retrograde tracer transport. Labeled motoneurons were found in the supraspinal nucleus of the lower brainstem and in the ventral horn of the upper cervical cord. Each of the craniocervical muscles appeared to be innervated by a separate motorpool, and pools supplying different muscles were found to overlap considerably. Despite this overlap, some organization pattern could be recognized: the most ventral muscles are innervated by motoneurons that occupy dorsomedial positions, while more dorsal muscles are innervated by neurons at ventro-lateral positions. Thirdly, the arrangement of motoneurons innervating different parts of three craniocervical muscles was investigated by means of retrograde tracer transport. This indicated that each muscle part is also innervated by a separate motor column, and that columns supplying parts of the same muscle have similar positions in transverse sections but are shifted with respect to each other in the longitudinal direction. The separate columns of one muscle mingle to form one main motorpool. These results are discussed with respect to observations in other animals. PMID- 7983374 TI - Cholecystokinin neurons in the developing visual cortex of normal and dark reared rats. Comparison with other peptidergic populations. AB - The laminar distribution and the density of cholecystokinin-like (CCK) neurons in the developing visual cortical areas (17, 18 and 18 a) were studied in Wistar rats that were reared under normal lighting conditions or in complete darkness. Immunocytochemistry on paraffin sections at postnatal days (P) 7, 14, 21, 30 and 60 showed that the density of CCK neurons in all visual areas of both groups of animals progressively increases from P7 to P21 but declines thereafter, to reach 50-75% of peak densities at P30. From P30 to P60 the density of CCK neurons in the visual cortex remains relatively unchanged in non-deprived animals, but increases slightly again in areas 17 and 18 a of dark reared rats. Fluctuations in the density of CCK neurons reflect changes in the number of immunoreactive neurons mainly present in layers IV-VI. It is concluded that the development of the CCK neurons in the rat visual cortex is minimally affected by light deprivation. PMID- 7983375 TI - Immunization with DNA. PMID- 7983376 TI - Amplified electrochemical immunoassay for thyrotropin using thermophilic beta NADH oxidase. AB - The use of the highly stable, pH insensitive flavoenzyme, reduced nicotinamide adenine dinucleotide oxidase (NADH oxidase) from the thermophilic organism Thermus aquaticus in combination with alcohol dehydrogenase in an amperometric amplified immunoassay for thyrotropin (TSH) is described. NADH oxidase catalyses the oxidation of reduced nicotinamide adenine dinucleotide (NADH) with concomitant two electron reduction of di-oxygen to hydrogen peroxide. Hydrogen peroxide can be detected by oxidation at a platinum electrode poised at +650mV vs. Ag/AgCl. The enzyme amplification system described has advantages over existing amplification techniques in terms of sensitivity, specificity and operational pH dependence. The electrochemical enzyme-amplified assay for TSH was compared with a spectrophotometric enzyme-amplified system and with a non amplified electrochemical immunoenzymometric TSH assay. The dynamic range of the electrochemical enzyme-amplified TSH immunoassay was 0.2-100 mIU/l, which was four times that of the enzyme-amplified spectrophotometric assay while the detection limits of both techniques were comparable. PMID- 7983378 TI - Increased sensitivity of diagnostic latex agglutination tests in an ultrasonic standing wave field. AB - A technique is described which increases the sensitivity of latex agglutination tests for soluble and particulate antigens. The levels of detection of tests for C-reactive protein and E. coli O157 respectively have been improved by x256 and x1024 compared with the standard test procedure of sample rotation on a test card. This new method combines dilution of the test latex particles, a 2 min sample treatment in the ultrasonic standing wave field of a tubular piezo electric transducer and subsequent examination by video-microscopy. Ultrasonic treatment is required to achieve increased localised concentrations of the latex particles in the standing wave field, and dilution of the latex is a critical requirement to allow agglutination to occur at low antigen concentrations. PMID- 7983377 TI - Isolation of mouse complement component C7. AB - Mouse complement component C7 was purified from serum by a sequential procedure of fractionation precipitation by ammonium sulfate, followed by DE-52 anion exchange chromatography. Protein G affinity column chromatography, Mono S cation exchange chromatography and Superdex 200 gel filtration. The final product contained a highly purified mouse C7 component showing a single band on SDS-PAGE at the apparent Mrs of 90 kDa and 100 kDa under non-reduced and reduced conditions respectively. The yield of C7, which was measured by the biological activity, was 7.0% PMID- 7983379 TI - An ear swelling reaction for in vivo monitoring of inflammatory T cell activity in collagen-arthritic rats. AB - T cells play a dominant role in the pathogenesis of collagen-induced arthritis (CIA). The effector mechanism involves a delayed-type hypersensitivity reaction in the synovial joint. Here we describe a new test system, named a flare reaction, to monitor directly this inflammatory T cell function. It is shown that type II collagen (CII) injected into the pinna of the ear is a target for CII reactive inflammatory T cells formed during the early pathogenesis of CIA. The inflammatory swelling of the joint and the CII-injected ear in CIA rats develop in a coordinated manner. This assay greatly facilitates monitoring of in vivo activated inflammatory T cells during the induction of CIA. PMID- 7983380 TI - Cross-reactivity of monoclonal antibodies to a chimeric V3 peptide of HIV-1 with peptide analogues studied by biosensor technology and ELISA. AB - The reactivity of monoclonal antibodies (Mabs) raised against a cyclic peptide representing a chimeric V3 loop of HIV-1 gp120 with different peptide analogues was studied with a biosensor system (BIAcore) and by ELISA. In both assays, the Mabs cross-reacted extensively with the V3 regions of different HIV-1 strains and recognized the cyclic form of the peptide immunogen better than its linear form. The highest degree of cross-reactivity was observed with peptides that shared a Lys312 with the chimeric sequence. Dissociation rate constants of ten Mabs measured with the BIAcore with respect to different peptides increased with increasing numbers of substitutions in the flanking regions of the V3 tip sequence Gly Pro Gly Arg. Immobilization of the cyclic peptide on the sensor chip via a thiol group added near the end of the loop structure preserved the conformation of the peptide. In view of the good correlation between the BIAcore and ELISA results, biosensor data should be useful for selecting peptides to be used in diagnostic solid phase assays. PMID- 7983381 TI - In situ transcription with Tth DNA polymerase and fluorescent nucleotides. AB - We and others have described methods to label specific nucleic acid sequences in fixed cells by reverse in situ transcription (IST). They are simple alternatives to the tedious steps of in situ hybridization with labeled probes. We have favored use of thermostable DNA polymerases after heat denaturation of template secondary structure, accompanied by synthesis of cDNA from an annealed primer, but the approach has been limited by the low reverse transcriptase (RT) activity of Taq polymerase and delayed detection methods. We have improved the technique by the use of recombinant Thermus thermophilus (rTth) DNA polymerase and fluorescein-12-dUTP (FIST). Jurkat T lymphocytes were stimulated with ionomycin + phorbol myristate acetate to produce interleukin-2 (IL-2) mRNA in vitro overnight. They were cytospun onto slides and fixed in 70% ethanol + 30% DEPC treated water, acetone, and air-dried. The slides were placed on a temperature controlled heating block, and the cell spot was covered with a plastic coverslip. The temperature was raised to 95 degrees C, and 5-10 microliters of modified Perkin-Elmer/Cetus rTth RT reaction mix was injected under the edge of the coverslip. Each 10 microliters of mix in DEPC-water contained 10 mM Tris-HCl, pH 8.3, 90 mM KCl, 1 mM MnCl2, 1 mM dithiothreitol, 10 U placental ribonuclease inhibitor, 0.125 mM dA,C,GTPs, 0.1 mM fluorescein-12-dUTP, 2 U rTth DNA polymerase, and 4 pM 22-mer oligonucleotide primer, which spanned the second intron of IL-2. After 3 min at 95 degrees C, 1 min at 50 degrees C and 10 min at 72 degrees C, the slides were washed in 0.5 x phosphate-buffered saline, pH 7.0, at 42 degrees C, in 70% ethanol, 100% ethanol, and air-dried. The cells were mounted in antifade solution (2% n-propyl gallate in 70% glycerol), and could be viewed immediately by fluorescence microscopy. Image analysis showed that stimulated Jurkat cells were brighter than uninduced controls or those treated with RNase or without polymerase or primer. FIST appears to be useful for the detection of specific mRNAs in single cells. PMID- 7983382 TI - Systematic identification of H-2 Kd binding peptides and induction of peptide specific CTL. AB - Most peptides with putative MHC I restricted sequence motifs do not bind to the corresponding MHC I nor induce cytolytic T cells. There exist additional constraints which limit peptide binding and immunogenicity. To identify immunogenic peptides in novel protein sequences, it will be necessary to first evaluate peptide binding to MHC I. In this study, a soluble single chain fusion protein SC-Kd was used to evaluate potential Kd binding peptides from the sequences of mouse mammary tumor virus gag and env proteins. A total of 27 peptides were identified which displayed the reported Kd restricted motif. Of the 27 peptides, six demonstrated strong to moderate binding to SC-Kd. The strongest binding peptides expressed tyrosine or phenylalanine at position 2 and leucine at the C-terminus. The capability of MMTV peptides to induce CTL corresponds to their SC-Kd binding activity. Of the six peptides that demonstrated moderate to strong binding, five induced CTL in BALB/c mice. These peptides induced CTL after 1-3 in vivo immunizations followed by 5 day in vitro stimulation. Furthermore, a single in vitro stimulation of naive lymphocytes with strong-binding G425 was sufficient to induce significant CTL activity. Weak or non-binding peptides did not induce CTL. Therefore, peptide binding to SC-Kd is a predictive indicator of CTL inducing activity. PMID- 7983383 TI - A rapid, single-step purification method for immunogenic members of the hsp 70 family: validation and application. AB - Gelatin affinity chromatography has been developed as a simple one-step procedure for purification of members of the hsp 70 kDa family from MDBK cells (a bovine epithelioid cell line), rat liver microsomes and three different protozoan parasites. The ability of the isolated proteins to bind to denatured proteins like gelatin together with their apparent molecular masses, constitutive and inducible expression and their release from gelatin-agarose beads by ATP suggested that these proteins are molecular chaperones. The identity of a gelatin bound, ATP released, 78 kDa protein isolated from rat liver was confirmed by comparison of its NH2-terminal sequence with that of grp 78/BiP from rat. A 68 kDa protein isolated from Trypanosoma brucei brucei (T.b. brucei) and proteins of 68 and 69 kDa from Leishmania donovani (L. donovani) using gelatin affinity chromatography reacted in Western blot analysis with a monoclonal antibody, 7.10, specific for members of the 70 kDa heat shock protein family derived from a wide variety of species. A different monoclonal antibody, SPA-820, which also recognises members of the hsp 70 kDa family, bound to proteins isolated from Theileria parva Muguga transformed lymphoblastoid cell lines (TpM). The gelatin bound ATP released proteins of 72 kDa from T.b. brucei and of 65, 69 and 72 kDa from TpM were detected by recovery sera of the cattle infected with T.b. brucei and T. parva, respectively. PMID- 7983384 TI - Targeted amplification of alternatively spliced transcripts of major histocompatibility complex class I heavy chain. AB - The RPMI1788 cell line was found to produce soluble form of HLA class I molecules (sHLA) constitutively, due at least in part to an alternative splicing mechanism in which exon 5 of HLA class I heavy chain transcripts is deleted. Reverse transcription-polymerase chain reaction (RT-PCR) of cytoplasmic RNA of RPMI1788 cells using a pair of primers (A,B) complementary to the conserved sequences of HLA class I exon 4 and 6 yielded almost exclusively the full-length class I heavy chain cDNA. In order to amplify the alternatively spliced transcripts, primer C corresponding to the 5' boundary conserved region of exon 6 juxtaposed with three conserved nucleotides in 3' boundary region of exon 4 was synthesized. Using the primers A and C the spliced transcripts of RPMI1788 cells can be selectively or preferentially amplified by RT-PCR with three different DNA polymerases. Cloning and sequencing of the resulting cDNA confirmed that the spliced transcript lacks exon 5. The targeted amplification method may be useful and important for studies with respect to the regulation of class I sHLA expression and the mechanism by which alternative splicing of HLA class I heavy chain mRNA is induced. PMID- 7983385 TI - A microscale method for depleting cross-reactive anti-antibodies used in indirect immunofluorescence microscopy. PMID- 7983386 TI - Technical issues related to checkerboard immunoblotting. PMID- 7983387 TI - Elimination of leprosy as a public health problem. PMID- 7983388 TI - Prospects of elimination of leprosy in India. PMID- 7983389 TI - Elimination of leprosy: forecasts and projections. PMID- 7983391 TI - Eustachian tube functions in lepromatous leprosy: a tympanometric study. AB - Tympanometry was performed in 20 patients with lepromatous leprosy. About 30% showed tympanogram B type indicating middle ear pathology which was shown to be related to the stage of lepromatous rhinitis. The pathogenesis of middle ear malfunction in lepromatous leprosy is discussed. PMID- 7983390 TI - Changing role of voluntary organizations in the context of elimination of leprosy. PMID- 7983392 TI - Oral zinc therapy in recurrent erythema nodosum leprosum: a clinical study. AB - Effect of oral zinc as an immunomodulator was studied clinically in patients with recurrent ENL over a period of one year. In this study, 40 leprosy patients with chronic ENL, requiring more than 30-40 mg of prednisolone/day for the control of their reactions, were given oral zinc sulphate for a period of four months, and, marked improvement in the frequency, duration and severity of reactions was observed after zinc therapy. Also evident was marked reduction in the steroid requirement after oral zinc therapy. It appears that zinc may be a good substitute for the present day anti-reaction treatment which is not free from disadvantages. Further investigations to know the precise action of zinc on immune-system may help to understand the role of zinc therapy and its optimum duration. PMID- 7983393 TI - Dapsone syndrome in Goa. AB - Daspone syndrome was noted within six weeks of starting treatment in 1.3% of about 700 leprosy patients on MDT reporting to the skin department of Goa Medical College. Skin rash, photosensitivity, fever, lymphadenopathy, sore throat, hepatosplenomegaly, abnormal liver function tests and raised reticulocyte count were consistent features in all the patients. Other drugs, infectious mononucleosis and viral exanthemata were considered in differential diagnosis. Withdrawal of dapsone and administration of prednisolone controlled the condition within three to four weeks in majority of the patients. One patient died of ischemic heart disease unrelated to dapsone syndrome. PMID- 7983394 TI - In vitro experiments with Centella asiatica: investigation to elucidate the effect of an indigenously prepared powder of this plant on the acid-fastness and viability of M. tuberculosis. AB - The herb Centella asiatica (Linn.), found throughout India, is acclaimed to have medicinal properties and has been used in leprosy patients from very early times. It is considered that the active compound of this herb, called asiaticoside, probably acts on the waxy covering of M. leprae. The in vitro effect of an indigenously produced dry powder of Centella asiatica (CA) on the acid-fastness and viability of M. tuberculosis was investigated in the present study. The results indicate that CA may not have any direct action on the acid-fastness or viability of M.tuberculosis H37Rv in vitro. Further studies using purified asiaticoside of the plant or in vivo studies are required. PMID- 7983395 TI - Cotrifazide. PMID- 7983397 TI - Detection of smear positive cases--need of the hour. PMID- 7983396 TI - Simpler procedures solve difficult problems. PMID- 7983398 TI - [Significance of emergency endoscopic examination and endoscopic hemostasis]. PMID- 7983399 TI - [Epidemiology of gastrointestinal hemorrhage]. PMID- 7983400 TI - [Esophageal varices]. PMID- 7983401 TI - [Mallory-Weiss syndrome]. PMID- 7983402 TI - [Dieulafoy ulcer]. PMID- 7983403 TI - [Vascular ectasia (angiodysplasia)]. PMID- 7983404 TI - [Acute gastric mucosal lesion]. PMID- 7983405 TI - [Antibiotic-related colitis]. PMID- 7983406 TI - [Ischemic disease of the large intestine and rectal hemorrhage]. PMID- 7983407 TI - [Immunologic occult blood tests--test methods and their evaluation]. PMID- 7983408 TI - [Radiological localization of the sites of gastrointestinal hemorrhage]. PMID- 7983409 TI - [Treatment of gastrointestinal hemorrhage. 1. Drug therapy]. PMID- 7983410 TI - [Treatment of gastrointestinal hemorrhage. 2. Endoscopic hemostatic techniques]. PMID- 7983411 TI - [Treatment of gastrointestinal hemorrhage. 3. Treatment of esophagogastric varices and long-term prognosis]. PMID- 7983412 TI - [Treatment of gastrointestinal hemorrhage. 4. Limitation of conservative treatment--with special reference to peptic ulcer. 1) A view from internal medicine]. PMID- 7983413 TI - [Treatment of gastrointestinal hemorrhage. 4. Limitation of conservative treatment--with special reference to peptic ulcer. 2) From the viewpoint of surgery]. PMID- 7983414 TI - [Management of gastrointestinal hemorrhage. Discussion]. PMID- 7983415 TI - [Acute myelocytic leukemia associated with Clostridium perfringens (CP) septicemia: report of 3 cases]. PMID- 7983416 TI - [Case of kidney cancer presenting an interesting example of paraneoplastic syndrome]. PMID- 7983417 TI - [Case of glycogen storage disease with accentuated myocardial hypertrophy and characteristic ECG changes in a 19-old man]. PMID- 7983419 TI - [Autopsy case of anti-neutrophil cytoplasmic antibody positivity with proven crescent-forming nephritis and interstitial pneumonia, followed by polyarteritis, Shonlein-Henock (S-H) purpura, respiratory insufficiency, and acute renal failure]. PMID- 7983418 TI - [Case of MCTD with recurrent pleuritis and high titers of anti-U1RNP antibody and immune complex in the pleural effusion]. PMID- 7983420 TI - [Case of neoplastic angioendotheliosis (angiotrophic B cell lymphoma)]. PMID- 7983421 TI - [Case of enteric hyperoxaluria resulting in calcium oxalate calculi following ileectomy]. PMID- 7983422 TI - [Parvovirus B19 infection: variable clinical presentations]. PMID- 7983423 TI - [Induction of leukemic cell differentiation]. PMID- 7983424 TI - [Clinical description of toxic shock-like syndrome]. PMID- 7983425 TI - Radiation damage in DNA: physics, chemistry and molecular biology. Proceedings of the 18th L.H. Gray conference. Bath, UK, 10-14 April 1994. PMID- 7983427 TI - RBE-LET relationships for different types of lethal radiation damage in mammalian cells: comparison with DNA dsb and an interpretation of differences in radiosensitivity. AB - Relative biological effectiveness (RBE), as a function of linear energy transfer (LET), is evaluated for different types of damage contributing to mammalian cell reproductive death. Survival curves are analysed assuming a linear-quadratic dose dependence of lethal lesions. The linear term represents lethal damage due to single particle tracks, the quadratic term represents lethality due to interaction of lesions from independent tracks. RBE-LET relationships of single track lethal damage, sublethal damage, potentially lethal damage and DNA double strand breaks (dsb) are compared. Single-track lethal damage is shown to be composed of two components: damage that remains unrepaired in an interval between irradiation and assay, characterized by a very strong dependence on LET, with RBEs up to 20, and potentially lethal damage, which is weakly dependent on LET with RBEs < 3. Potentially lethal damage and sublethal damage depend similarly on LET as DNA dsb. The identification of these different components of damage leads to an interpretation of differences in radiosensitivity and in RBEs among various types of cells. PMID- 7983426 TI - The complexity of DNA damage: relevance to biological consequences. AB - Ionizing radiation causes both singly and multiply damaged sites in DNA when the range of radical migration is limited by the presence of hydroxyl radical scavengers (e.g. within cells). Multiply damaged sites are considered to be more biologically relevant because of the challenges they present to cellular repair mechanisms. These sites occur in the form of DNA double-strand breaks (dsb) but also as other multiple damages that can be converted to dsb during attempted repair. The presence of a dsb can lead to loss of base sequence information and/or can permit the two ends of a break to separate and rejoin with the wrong partner. (Multiply damaged sites may also be the biologically relevant type of damage caused by other agents, such as UVA, B and/or C light, and some antitumour antibiotics.) The quantitative data available from radiation studies of DNA are shown to support the proposed mechanisms for the production of complex damage in cellular DNA, i.e. via scavengable and non-scavengable mechanisms. The yields of complex damages can in turn be used to support the conclusion that cellular mutations are a consequence of the presence of these damages within a gene. Literature data are used to support these statements and to develop overall mechanisms connecting the production of primary species to the production of biologically relevant damages. The consequences of the LET of the radiation on multiplicity of damage are discussed and suggestions made for the cause of the decrease of the oxygen enhancement ratio as the LET increases. PMID- 7983428 TI - Double-strand breaks from 125I incorporated in the DNA and cell death. AB - Track structure calculations of the local energy deposition by electrons emitted during the decay of 125I are used to demonstrate that the range of high energy deposition is small (< 10 nm) and restricted to the DNA and its immediate environment. An experiment in which 125I is incorporated into the DNA of synchronized CHO cells during a pulse and decays are allowed to accumulate a given time after the incorporation is described. Here it is shown that damage from 125I decays in newly replicated DNA (cells frozen for decay accumulation within 1 h after labelling) are relatively non-toxic whereas decays in mature DNA (cells frozen 5 h after labelling) are highly lethal. It is suggested that during DNA maturation the labelled DNA becomes associated with (or reorganized into) a radiosensitive nuclear structure and that damage to this structure is the primary cause of radiation-induced cell death. PMID- 7983430 TI - Modelling of radiation damage by 125I on a nucleosome. AB - Studies of early physical interactions of ionizing radiation in biological medium have evolved from water cylinders or spheres to structured volumes representing nucleosomal DNA, based on spatial co-ordinates for each individual atom. Regarding the physico-chemical and chemical stages, the models of DNA have evolved from inactive geometrical objects to active participation of DNA in the reactions with the radical species. In this paper data are presented on the modelling of the interaction of low energy electrons with nucleosomal DNA. The nucleosome core unit has been modelled as a 146-bp helical DNA, containing > 9000 atoms, wound around the core unit. The yields of strand breaks for low energy electrons has been obtained by placing the nucleosome target in a liquid water environment and introducing a number of assumptions for the induction of strand breaks. The calculated results for the induction of ssb and dsb by 125I decays agree with experimental data, confirming the plausibility of this nucleosome model as well as the characterization of the interaction of ionizing radiation in terms of the energy deposition and the assumptions made for the strand breaks. PMID- 7983429 TI - A comparison of DNA damages produced under conditions of direct and indirect action of radiation. AB - Studies using a 32P-postlabelling assay reveal that at both low and high concentrations of hydroxyl radical scavenger, DNA damage from alpha-irradiation is similar to that from gamma-irradiation. At low concentrations of scavenger the identified damages are predominantly thymine glycol (Tg) and phosphoglycolate (pg) lesions, indicative of indirect hydroxyl radical (.OH) action. However, at high concentrations of scavenger (i.e. where direct effects are expected to dominate) a somewhat different pattern of damage is observed after alpha- and gamma-irradiation, with several novel lesions detected. Further experiments, in which the results of DMSO scavenging of irradiated DNA solutions are compared with glycerol scavenging and irradiation of 'dry' solid DNA, demonstrate that both direct effects and scavenger-derived secondary radicals contribute to the different spectra of lesions observed upon irradiation of highly scavenged DNA systems. Generally, irradiation under conditions that favour direct damage result in a lower relative yield of pg, whilst for the highly scavenged systems Tg damages persist. To account for this we propose that Tg are efficiently produced by direct action in these systems. Differences seen upon irradiation of the 'dry' system, compared with those of dilute aqueous solution, suggest that direct action yields a distinct spectrum of lesions. PMID- 7983431 TI - Modelling of radiation-induced DNA damage: the early physical and chemical event. AB - A Monte Carlo track structure calculation of single- and double-strand breaks induced by direct energy deposition in DNA and by interacting diffusible .OH radicals with DNA has been made for low energy electrons. The .OH radicals generated within 4 nm of linear segments of DNA were diffused in order to mimic the mean diffusion distance in the cellular environment. The reactions of the radical species .OH, .H and e-aq were included in this study. The calculated values for the yield of single- and double-strand breaks have been compared with experimentally determined values from the literature. The calculations indicate, too, that the majority of dsb have additional associated damage, constituting clustered lesions of varying complexity. PMID- 7983432 TI - Molecular damage induced directly and indirectly by ionizing radiation in DNA. AB - We describe the interaction of radiation with a double-stranded DNA molecule and with the structural water surrounding it. The results, which include a detailed picture of DNA molecular alterations, as well as their yield and spatial disposition, were obtained with the aid of Monte Carlo codes that simulate, event by-event and simultaneously, direct and indirect effects. These calculations make use of explicit quantum-mechanical descriptions of the electronic structure of condensed water and of a homopolynucleotide chain. From these we obtain, via the dielectric response function of the two systems, epsilon (q, omega), the interaction probabilities necessary in the transport codes. PMID- 7983433 TI - Simple and complex double-strand breaks induced by electrons. AB - Biophysical modelling of DNA damage based on Monte Carlo simulation of charged particle tracks allows to describe radiation induced double-strand breaks (dsb) in a quantitative and qualitative way. Experimental and calculated data suggest that in the electron energy range from 50 eV to 1 MeV dsb can be grouped in simple and complex dsb. Complex dsb are mainly produced by low energy electrons with initial energies between approximately 200 and approximately 500 eV, whereas simple dsb are preferentially induced by energy transfers < 200 eV, which produce at least two ionizations. PMID- 7983434 TI - DNA structure, hydration and dynamics. AB - Although the double helical model of DNA structure is now 40 years old, there is still considerable effort being made to elucidate the range of conformations that can be adopted by this flexible molecule. We review the current state of our knowledge of DNA structure which is available from both experimental and computational approaches. PMID- 7983435 TI - Metal-ion assisted, radiation-induced conversion of B- to Z-DNA in poly (dGdC) and two natural DNAs. AB - Metal-ion assisted, gamma-radiation-induced B-Z conformation changes have been observed with UV and circular dichroism spectroscopy for poly (dGdC), calf thymus and herring testis DNA. These conformational changes are similar to those induced by increasing multivalent metal ion concentrations in DNA containing alternating purine and pyrimidine base sequences. In both the metal-ion-induced and the metal ion-assisted, radiation-induced conformation changes, the conversions were from the right-handed B-DNA to the left-handed Z-DNA conformation. It is proposed that radiation-induced DNA strand breaks markedly reduce the high activation energy barrier in the metal ion-driven B-Z conformation conversion and allow much smaller metal ion concentrations to induce this conversion than in the absence of strand breaks. The biological importance of such radiation-induced conformational changes is discussed in terms of the potential significance of the Z-DNA conformation in the control of the DNA transcription process. PMID- 7983436 TI - Combination is the dominant free radical process initiated in DNA by ionizing radiation: an overview based on solid-state EPR studies. AB - An overview of the early processes initiated in DNA by ionizing radiation is given from the perspective of studies done by solid-state EPR with the focus on radical combination. Comparisons with free radical formation and trapping in crystalline pyrimidines (1-methylcytosine, thymine, 1-methylthymine, 1 methyluracil, and cytosine monohydrate) provide insight into the processes occurring in DNA. Between 25 and 50% of low LET ionizations in fully hydrated DNA at 4 K lead to trapped free radicals, the remaining unobserved radicals are assumed to have combined. The majority of the radicals trapped in DNA at 4 K (G approximately 0.3 mumol/J) are believed to be in clusters. Based on the value of G, it is argued that the range of holes and bound electrons in DNA at 4 K are, in the main, limited to within the cluster diameter, approximately 4 nm. Proton transfer across hydrogen bonds promotes radical trapping and inhibits combination but is thermally reversible. Warming to room temperature mobilizes the reversibly trapped radicals and gives additional combination (50-80% of those trapped at 4 K). The yield of free radicals, after anneal, is sufficient to account for the yield of single-strand breaks produced by direct effects. PMID- 7983437 TI - Influence of nucleic acid base composition on radiation-induced strand breakage in single stranded DNA: a time resolved study. AB - The following study investigates the pathways involved in the induction of single strand breaks (ssb) in various samples of single stranded (ss) DNA (calf thymus, Micrococcus lysodeikticus, Clostridium perfringens) with differing nucleic acid base composition. The time scale for the induction of ssb was determined from changes in the light scattering intensity following pulse irradiation of aqueous solutions containing these ssDNA samples at pH7.8 under either aerated or deaerated conditions. The induction of ssb under these conditions is predominantly by the hydroxyl radical and shows various kinetically distinct components. The immediate ssb (t < 0.02 s) account for approximately 40-60% of the total yield of ssb. The majority of these ssb are suggested to arise from the 'common' initial attack of the hydroxyl radicals at the sugar phosphate backbone for each of the three DNA samples. Furthermore, slower components for ssb formation (t > 0.02 s) were observed and are suggested to occur through base radical mediated H-atom abstraction from the sugar moiety. The half lives for formation of the majority of ssb, formed through this base radical-mediated H atom abstraction(s), are in the range of 20-43 ms. The yields of these 'base mediated' ssb vary markedly (under both aerobic and anaerobic conditions) and reflect the base composition of the DNA sample. It is suggested from these studies that the OH-induced base radicals of guanine/cytosine are more effective precursors for strand breakage than those from adenine/thymine in ssDNA. PMID- 7983438 TI - Radiation-induced electron migration in nucleic acids. AB - Radiation-induced electron migration along DNA is a mechanism by which randomly produced stochastic energy deposition events can lead to non-random types of damage along DNA manifested distal to the sites of the initial energy deposition. Radiation-induced electron migration in nucleic acids has been examined using oligonucleotides containing 5-bromouracil (5-BrU). Interaction of 5-BrU with solvated electrons results in release of bromide ions and formation or uracil-5 yl radicals. Monitoring either bromide ion release or uracil formation provides an opportunity to study electron migration processes in model nucleic acid systems. Using this approach we have discovered that electron migration along oligonucleotides is significantly influenced by the base sequence and strandedness. Migration along 7 base pairs in oligonucleotides containing guanine bases was observed for oligonucleotides irradiated in solution, which compares with mean migration distances of 6-10 bp for Escherichia coli DNA irradiated in solution and 5.5 bp for E. coli DNA irradiated in cells. Evidence also suggests that electron migration can occur preferentially in the 5' to 3' direction along a double-stranded oligonucleotide containing a region of purine bases adjacent to the 5-BrU moiety. Our continued efforts will provide information regarding the contribution of electron transfer along DNA to formation of locally multiply damaged sites created in DNA by exposure to ionizing radiation. PMID- 7983439 TI - DNA in glasses at 77 K: high energy ionizing radiation versus UV electron ejection. AB - Most in the field of ionizing radiation damage to DNA in frozen aqueous solutions agree that two major types of radical ions are formed, i.e. G+/A+ and T-/C-. The main evidence stems from EPR and strand break studies. Fluid solutions exposed to laser light are known to give G+ and esolv- with low yields of single strand breaks. We have explored this contrast by photoionizing DNA solutions at 77 K, in the expectation that this would prevent the formation of esolv- and hence that the results might be similar to those for high energy radiation. They are not: the results show only the formation of G+ (or) (A+), the fate of the ejected electrons is unclear except for sodium perchlorate glasses when they react to give O-. PMID- 7983440 TI - Nuclear structure and the microdistribution of radiation damage in DNA. AB - Evidence for the roles of proteins and metal ions in the microheterogeneity of DNA damage is reviewed. Decondensation of chromatin in hypotonic buffers markedly sensitizes the DNA to radiation, while treatment of nuclei with hypertonic buffers strips the DNA of histones and other nuclear proteins and enhances the radiosensitivity of the DNA with respect to double-strand break (dsb) formation. Addition of the radical scavenger DMSO reduces the yield of strand breaks, but dehistonized chromatin remains approximately 2.5 times more sensitive to radiation than does native chromatin at 0.1 M DMSO. DNA-protein crosslink (DPC) formation is relatively unaffected by the removal of the majority of histones from chromatin. Most DPC form at or near the nuclear matrix, and matrix is stabilized and radiosensitized by Cu++. To elucidate the role of Cu++, the induction of dsb and DPC by gamma-radiation has been compared with that by hydroxyl radical from Fe(++)-EDTA, or Cu++ catalysed Fenton reactions. Data comparing the size of DNA fragments produced, the effect of expanding or dehistonizing chromatin, and the effects of radical scavengers suggest that gamma radiation and Fe(++)-EDTA produce dsb at open chromatin sites, whereas Cu(++) generated dsb are similar to radiation-induced DPC in their location at the nuclear matrix. Both metal ions appeared to produce damage by site-specific generation of hydroxyl radicals. The nuclear matrix, the proteinaceous skeleton which anchors chromosomal loops and provides sites for DNA replication and transcription, binds metal ions and matrix-attachment DNA regions (MARs) consisting of 300 + bp of AT-rich DNA. The interaction of cloned MARs with isolated nuclear matrices has been found to be hypersensitive to crosslinking upon gamma-irradiation, in comparison with associations formed by similarly sized DNA fragments lacking MAR sequences. Thus, the non-random distribution of radiation damage is partially explained by the protection of DNA afforded by histones and chromatin structure and partially by the hypersensitivity of DNA nuclear matrix associations. PMID- 7983441 TI - A component of DNA double-strand break repair is dependent on the spatial orientation of the lesions within the higher-order structures of chromatin. AB - By the use of a modified neutral filter elution procedure variations in the repair of DNA dsb have been observed between the ionizing radiation sensitive mutant xrs-5 and the parent cell line CHO-K1. Conventional neutral filter elution requires harsh lysis conditions to remove higher-order chromatin structures which interfere with elution of DNA containing dsb. By lysing cells with non-ionic detergent in the presence of 2 mol dm-3 salt, histone-depleted structures that retain the higher-order nuclear matrix organization, including chromatin loops, can be produced. Elution from these structures will only occur if two or more dsb lie within a single-looped domain delineated by points of attachment to the nuclear matrix. Repair experiments indicate that in CHO cells repair of dsb in loops containing multiple dsb are repaired with slow kinetics whilst dsb occurring in loops containing single dsb are repaired with fast kinetics. Xrs-5 cells are defective in the repair of multiply damaged loops. This work indicates that the spatial orientation of dsb in the higher-order structures of chromatin are a possible factor in the repair of these lesions. PMID- 7983442 TI - Effect of radiation quality on lesion complexity in cellular DNA. AB - Understanding the critical lesions induced by ionizing radiation in DNA and their relationship to cellular effects is an important challenge in radiation biology. Much evidence has suggested that DNA double-strand breaks (dsb) are important lesions. Establishing a cause and effect relationship between initial levels of DNA dsb, their repair rate or the level of residual unrepaired breaks, and cellular effects has proved difficult in mammalian cells. Several studies have measured yields of DNA dsb after irradiation with radiations of differing linear energy transfer (LET). In general the RBEs for dsb induction (20-100 keV/microns) have been lower than the RBEs measured for cell survival and in many cases are around 1.0. Several studies have shown differences in the rejoining of dsb with less dsb rejoined after high-LET irradiation in comparison with low-LET radiation. These results suggest that there may be differences in the types of lesions induced by different radiations and scored as DNA dsb using current techniques. Track structure modelling studies have suggested that some lesions induced will be clustered at the sites of energy depositions and that uniquely large energy deposition events are produced by high-LET radiations. Assays need to be developed to measure complex lesions in both model DNA and cellular systems. Different levels of complexity need to be considered such as clustering of radicals close to DNA, localized areas of DNA damage (1-20 bp) and lesions which may be induced over larger distances. Studies using new and existing assays of DNA damage, coupled with irradiation at various LETs, are directed at understanding the role of lesion complexity in relation to cellular effects. PMID- 7983443 TI - Half-life values for DNA double-strand break rejoining in yeast can vary by more than an order of magnitude depending on the irradiation conditions. AB - Yeast cells in stationary phase were exposed under oxic or anoxic conditions to sparsely (30 MeV electrons) or densely (3.5 MeV alpha-particles) ionizing radiation. For all four experimental set-ups postirradiation treatment of cells was the same, i.e. cells were kept under oxic conditions in non-growth medium at 30 degrees C. Double-strand break (dsb) rejoining was measured during this treatment yielding the following results: (1) half-life values ranged from < 60 min (electrons, anoxia) to 3.8 h (low doses of electrons, oxia), 7 h (alpha particles, anoxia), 10 h (high doses of electrons, oxia) and 13 h (alpha particles, oxia). (2) In the case of exposure of oxic cells to electrons a biphasic rejoining kinetics is observed with a dose-dependent increase of the fraction of the slow component. These results suggest that half-life values of dsb rejoining in a given cell depend on physical, chemical and biological parameters. The rejoining of dsb slows down with increasing LET, being probably due to the increasing complexity of dsb. Oxygenation of cells at the time of irradiation affects half-life values, indicating that radiation chemistry plays an important role. The biphasic rejoining kinetics observed for dsb induced by electrons in oxic cells is interpreted in terms of a dose-dependent change of chromatin structure hindering the interaction between damaged chromatin and the rejoining enzymes rather than by two chemically distinct types of dsb with differing half-life values. PMID- 7983444 TI - On the linearity of the dose-effect relationship of DNA double strand breaks. AB - Most radiation biologists believe that DNA double-strand breaks are induced linearly with radiation dose for all types of radiation. Since 1985, with the advent of elution and gel electrophoresis techniques which permit the measurement of DNA double-strand breaks induced in mammalian cells at doses having radiobiological relevance, the true nature of the dose-effect relationship has been brought into some doubt. Many investigators measured curvilinear dose-effect relationships and a few found good correlations between the induction of the DNA double-strand breaks and cell survival. We approach the problem pragmatically by assuming that the induction of DNA double-strand breaks by 125I Auger electron emitters incorporated into the DNA of the cells is a linear function of the number of 125I decays, and by comparing the dose-effect relationship for sparsely ionizing radiation against this standard. The conclusion drawn in that the curvilinear dose-effect relationships and the correlations with survival are real. The problem of why the dose-effect relationship is curvilinear when microdosimetric considerations predict that even for sparsely ionizing radiation energy deposition in and close to the Watson-Crick double helix should give a linear dose-effect relationship remains. PMID- 7983445 TI - Non-reparable DNA strand breaks and cell killing studied in CHO cells after X irradiation at different passage numbers. AB - Non-reparable DNA strand breaks were measured in X-irradiated CHO cells by means of the alkaline unwinding technique and were compared with cell survival measured by the colony assay. The experiments were performed with cells at passage numbers 10, 50 and 110 after thawing from stock culture. Cellular radiosensitivity was found to be identical for all three passage numbers used. By contrast, the dose response of non-reparable DNA strand breaks was only the same for passage numbers 10 and 50 but significantly steeper for cells irradiated in passage number 110. The ratio of non-reparable breaks to lethal events, as calculated from the survival curves, was found close to 1:1 for cells irradiated at passage numbers 10 and 50 but increased to 20:1 at passage number 110. These data indicate that the number of non-reparable strand breaks measured after irradiation not only depends on cellular radiosensitivity but also on other parameters such as the age of the cell culture. PMID- 7983446 TI - p53 status, DNA double-strand break repair proficiency, and radiation response of mouse lymphoid and myeloid cell lines. AB - The p53 status of a panel of 10 mouse lymphoid or myeloid cell lines was determined by immunoprecipitation with mutant- and wild-type-specific antibodies and was compared with the radiation response of the lines. The more rapidly dying cell lines all contained p53 displaying the wild-type epitope. By contrast, four of six more slowly dying cell lines contained either no or mutant p53 protein. It was of interest that radiation-induced apoptosis occurred, albeit at a considerable time after irradiation, in cells ostensibly lacking p53 protein. DNA double-strand break (dsb) repair was examined in both a rapidly and more slowly dying cell line. The rapidly dying cell line was capable of DNA dsb rejoining, however this repair was interrupted by postirradiation DNA degradation. PMID- 7983447 TI - DNA damage induced by vacuum and soft X-ray photons from synchrotron radiation. AB - The recent development of irradiation systems using synchrotron radiation (SR) as a source is enabling researchers to obtain intense monochromatic photons having a narrow bandwidth in the vacuum-UV (VUV) and soft X-ray regions. We can thus systematically study the photon energy dependence of DNA damage formation in these energy regions. The photon energy dependence provides useful information about how energy-absorbing modes--excitations, so-called superexcitations, outer- and inner-shell ionizations--affect the type and amount of DNA damage. Furthermore, low energy electrons produced by low energy photons through photoelectric interactions are useful for studying how the electron energy affects the induction of DNA damage. A report is given on the present status of the SR irradiation systems in Japan as well as some results concerning the formation of DNA damage, in vitro and in vivo, by monochromatic photons in the VUV and soft X-ray regions. PMID- 7983450 TI - DNA damages processed by base excision repair: biological consequences. AB - Base damages, sugar damages, and single-strand breaks produced by free radicals are the preponderant lesions produced in DNA by ionizing radiation. These lesions have been individually introduced into substrate, template, and biologically active DNA molecules and enzymatic processing and biological consequences determined. Free radical-induced DNA lesions are processed by base excision repair and many are potentially lethal in simple viral systems. Furthermore, a number of free radical modifications of purine and pyrimidine bases are premutagenic lesions. The results of the enzymatic and biological processing of a number of the more well-studied and stable lesions are summarized. PMID- 7983448 TI - Action spectra for single- and double-strand break induction in plasmid DNA: studies using synchrotron radiation. AB - Ionizing radiations deposit a wide range of energies in and around DNA and this leads to a corresponding spectrum of complexity of the lesions induced. The relationships between the amount of energy deposited and the yields and types of damage induced are important in modelling the physical and chemical stages of radiation effect and linking them to biological outcome. To study these relationships experimentally, plasmids were mounted as a monolayer and exposed in vacuum to near-monoenergetic photons from the Daresbury Synchrotron. After irradiation, the DNA was washed off and assayed for single-(ssb) and double strand breaks (dsb) using agarose gel electrophoresis. Dose-effect relationships for ssb and dsb induction were obtained at various energies in the range 8-25 eV. The initial responses in the low-dose region allowed damage yields to be estimated. However, a common feature is that the responses showed energy dependent plateaus at higher doses as if a fraction of the DNA were shielded. Various measures were taken both to minimize and to correct for this effect. The data appear to show that the yields of ssb and dsb increase only slowly with photon energies > 10 eV, with a suggestion of similar threshold energies for both lesions. In the energy range covered, the yield of ssb is 12-20-fold greater than that of dsb. The data indicate that ssb and dsb may have a common precursor in this system. Earlier work with low-energy electrons showed that at 25 eV ssb were induced but no dsb were detected. PMID- 7983449 TI - Cloning human DNA repair genes. AB - Many human genes involved in the repair of UV damage have been cloned using different procedures and they have been of great value in assisting the understanding of the mechanism of nucleotide excision-repair. Genes involved in repair of ionizing radiation damage have proved more difficult to isolate. Positional cloning has localized the XRCC5 gene to a small region of chromosome 2q33-35, and a series of yeast artificial chromosomes covering this region have been isolated. Very recent work has shown that the XRCC5 gene encodes the 80 kDa subunit of the Ku DNA-binding protein. The Ku80 gene also maps to this region. Studies with fission yeast have shown that radiation sensitivity can result not only from defective DNA repair but also from abnormal cell cycle control following DNA damage. Several genes involved in this 'check-point' control in fission yeast have been isolated and characterized in detail. It is likely that a similar checkpoint control mechanism exists in human cells. PMID- 7983451 TI - The study of responses to 'model' DNA breaks induced by restriction endonucleases in cells and cell-free systems: achievements and difficulties. AB - The use of restriction endonucleases (RE) as a means of implicating DNA double strand breaks (dsb) in cellular responses is reviewed. The introduction of RE into cells leads to many of the responses known to be characteristic of radiation damage--cell killing, chromosomal aberration, oncogenic transformation, gene mutation and amplification. Additionally, radiosensitive cell lines are hypersensitive to RE, including those from the human disorder ataxia telangiectasia. However, quantitation of response and comparisons of the effectiveness of different RE are difficult, partly because of unknown activity and lifetime of RE in the cell. RE-induced dsb have also been used to reveal molecular mechanisms of repair and misrepair at specific sites in DNA. Dsb have been implicated in recombination processes including those leading to illegitimate rejoining (formation of deletions and rearrangements) at short sequence features in DNA. Also model dsb act as a signal to activate other cellular processes, which may influence or indirectly cause some responses, including cell death. In these signalling responses the detailed chemistry at the break site may not be very important, perhaps explaining why there is considerable overlap in responses to RE and to ionizing radiations. PMID- 7983452 TI - Responses of radiosensitive repair-proficient cell lines to restriction endonucleases. AB - Radiosensitive mutant mammalian cell lines fall into two categories: (1) those exhibiting a deficiency in the rejoining of dsb, e.g. Chinese hamster xrs and XR1, and murine scid cells; and (2) those exhibiting apparently normal rejoining of bulk dsb, e.g. hamster irs mutants and cells from ataxia-telangiectasia individuals. Cells of both types also show hypersensitivity to restriction endonucleases when applied by cell poration techniques. These data are reviewed, and new data are presented for Pvu II treatment of the radiosensitive dsb repair proficient Chinese hamster VC4 mutant, which has been reported to have normal cellular and chromosomal sensitivity to restriction endonucleases and neutrons. We find that VC4 is hypersensitive to blunt-ended dsb generated by PvuII. We conclude that the enhanced sensitivity of this and other repair-proficient mutants to radiation and restriction endonucleases results from a dsb processing defect leading to abnormal conversion of dsb into chromosomal aberrations. PMID- 7983453 TI - Radiation-induced genomic instability. AB - Quantitative assessment of the heritable somatic effects of ionizing radiation exposures has relied upon the assumption that radiation-induced lesions were 'fixed' in the DNA prior to the first postirradiation mitosis. Lesion conversion was thought to occur during the initial round of DNA replication or as a consequence of error-prone enzymatic processing of lesions. The standard experimental protocols for the assessment of a variety of radiation-induced endpoints (cell death, specific locus mutations, neoplastic transformation and chromosome aberrations) evaluate these various endpoints at a single snapshot in time. In contrast with the aforementioned approaches, some studies have specifically assessed radiation effects as a function of time following exposure. Evidence has accumulated in support of the hypothesis that radiation exposure induces a persistent destabilization of the genome. This instability has been observed as a delayed expression of lethal mutations, as an enhanced rate of accumulation of non-lethal heritable alterations, and as a progressive intraclonal chromosomal heterogeneity. The genetic controls and biochemical mechanisms underlying radiation-induced genomic instability have not yet been delineated. The aim is to integrate the accumulated evidence that suggests that radiation exposure has a persistent effect on the stability of the mammalian genome. PMID- 7983454 TI - Chromosomal instability and alterations of telomeric repeats in irradiated human fibroblasts. AB - In recent years, evidence has been presented suggesting that genomic instability can appear several generations after cellular exposure to radiations. Kadhim et al. (1992) have shown that irradiation by alpha-particles of Pu238 (LET = 120 keV/microns) induce a transmissible instability in mouse haematopoietic cells. Working with human dermis fibroblasts irradiated by heavy ions in a large range of LETs (386-13,600 keV/microns), we demonstrated that an instability could also be acquired by human cells and that particular chromosomes (13, 16, 1) were recurrently involved in telomeric associations (Sabatier et al. 1992). This instability resulted in specific chromosome imbalances and in a particular monosomy 13 (Martins et al. 1993). In this study, we wanted to determine whether telomeres are shortened with the appearance of the chromosomal instability. Our results show no drastic shortening of the mean length of telomeres by Southern blot. By in situ hybridization we are looking to see if chromosomes specifically involved in instability have alterations of the telomeres. We have observed large variations of the hybridization signal of individual telomeres with no telomeric sequences detectable at the junction of end to end associations. PMID- 7983456 TI - Influence of radiation quality on the expression of chromosomal damage. AB - The amount of chromosomal damage induced in synchronous V79 cells by either 250 kV X-rays or 4.6 MeV/u Ar ions (LET: 1850 keV/microns) was determined at five successive sampling times. The experiments show that the time course of the appearance of damaged cells is strongly influenced by radiation-induced cell cycle perturbations and mitotic delay and depends on radiation quality and dose. The yield of chromosomal damage was found to increase with sampling time, but this increase was more pronounced for Ar ions. Because of the observed differences in the yield time profiles induced by sparsely and densely ionizing radiation the contribution of each sample to the overall damage was considered, i.e. the total (time integrated) amount of damage was determined. The obtained data are interpreted in terms of differences in the spatial energy deposition by sparsely and densely ionizing radiation. PMID- 7983455 TI - Recent developments in the assessment of chromosomal damage. AB - Ionizing radiation and restriction endonucleases are very efficient in inducing chromosomal aberrations (CAs). These aberrations are mainly consequences of misrepair of DNA double-strand breaks (DSBs). The fast repairing component of DSBs induced by ionizing radiation seems to be responsible for exchange aberration. Use of premature chromosome condensation technique in combination with DNA repair inhibitors such as ara A has given valuable information on the assessment of the frequencies of initial chromosome breaks and the kinetics of their repair following low LET radiation. The recently developed 'chromosome painting' technique using chromosome-specific libraries has also increased considerably the resolution of identifying and scoring of CAs. After low LET radiation, stable chromosome exchanges (translocations) are induced more frequently than unstable chromosome exchanges (dicentrics). Fluorescence in situ hybridization employing telomeric probe has made it possible to score efficiently exchange aberrations involving the acrocentric chromosomes of mouse. Chinese hamster cells have several intercalary telomeric sequences present in most of the chromosomes. These telomeric blocks have been found to be associated with chromosomal aberrations induced by restriction endonucleases and short wave UV and evidence has been obtained for apparent amplification of telomeric sequences at the break points. PMID- 7983457 TI - Identification of X-ray-induced complex chromosome exchanges using fluorescence in situ hybridization: a comparison at two doses. AB - Complex chromosome exchanges are defined as interactions between three or more breaks, in two or more chromosomes. In this study, a sequential hybridisation technique was developed to visualize a given chromosome pair: green (chromosomes 1, 5 and 7), all centromeres red and the remaining chromosomes blue. Primary human fibroblasts were irradiated in G1 with 4 and 6 Gy 250-kV X-rays. After 4 Gy, a total of 387 simple aberrations (defined as translocations or dicentrics with fragments) and 116 complex aberrations were identified. After 6 Gy these aberrations numbered 225 and 110 respectively. Using a break-rejoin scheme, which describes interactions between breaks within a complex as independent events we modelled the complex 'mix' present after 4 Gy. At 6 Gy the same model could be used for chromosomes 5 and 7, but chromosome 1 frequencies could only be explained if we biased the interactions, such that two-breaks-in-one-chromosome events occur predominantly in chromosome 1. From these predicted interactions we also calculated the number of apparently simple exchanges that are actually complex derived. These accounted for 20% of those observed after 4 Gy and 33% after 6 Gy. Therefore, with this FISH assay, an estimated 35 and 54% of all exchanges are derived from complexes after 4 and 6 Gy respectively. PMID- 7983458 TI - Modelling of DNA breaks and the formation of chromosome aberrations. AB - We present results of some calculations that convert double-strand breaks to dicentrics by means of a repair-misrepair model. The method uses Monte Carlo techniques to determine the positions of the double-strand breaks and to determine the dicentric yields for comparison with those obtained experimentally in human lymphocytes following irradiation in G0. The model is able to describe the linear-quadratic curves of dicentric yield following low LET irradiation, but underpredicts by a factor of about 1.5-2.0 the high LET neutron curves. The effects of including corrections for interphase death are demonstrated. The reasons for the discrepancy at high LET are discussed and suggestions for an improvement to the fit are made. PMID- 7983459 TI - Relationship between chromosome aberrations, micronuclei and cell kill in two human tumour cell lines of widely differing radiosensitivity. AB - The relationship between chromosome aberration frequency, micronucleus (MN) formation and cell kill was investigated in two human tumour cell lines, RT112, a radioresistant bladder carcinoma cell line, and HX142, a radiosensitive neuroblastoma cell line. As MN are generally accepted to result from acentric chromosome fragments that are lost at nuclear division and all unstable aberrations result in an acentric fragment, a 1:1 correlation between aberrations and MN might be expected. There was a good correlation between cell kill and aberration frequency in the two cell lines, however the relationship between cell kill and MN formation in the lines was very different. RT112 showed 0.22 aberrations and 0.21 MN per Gy whilst HX142 showed 0.61 aberrations and 0.078 MN per Gy. Possible reasons for the discrepancy observed in HX142 are discussed. PMID- 7983460 TI - Human cancer predisposition and the implications for radiological protection. AB - It is well established from clinical, epidemiological and laboratory studies that specific human germ line mutation can predispose to spontaneously arising cancer. Some of the responsible genes have been characterized at the molecular level and evidence is rapidly accumulating on mechanistic aspects of the problem. A major outstanding issue is the extent to which genetically determined cancer predisposition in man interacts with exposures to environmental genotoxic agents such as ionizing radiation. This brief review considers the current position regarding the different forms and frequencies of cancer-predisposing mutations in the human population and provides an interim view of the possible implications for protection of man from ionizing radiation. PMID- 7983461 TI - Radon-induced cancer: a cell-based model of tumorigenesis due to protracted exposures. AB - In 1982, results with C3H mouse embryo cells showed that the frequency of neoplastic transformation was enhanced when exposures to fission-spectrum neutrons were protracted in time. This finding was unexpected because the opposite was found with low-LET radiations. Similar neutron enhancements were reported with normal life-span Syrian hamster embryo cells, and with human hybrid cells. Because other studies did not confirm the preceding, in 1990--at a conference convened by the US Armed Forces Radiobiological Research Institute--a biophysical model was proposed to explain the basis for the enhancement observed in some experiments but not in others. The model attributed special sensitivities, related to killing and neoplastic transformation, to cells in and around mitosis. Subsequently, it was shown that late G2/M phase cells constituted this window of sensitivity. In the instance of tumorigenesis, the model predicted that protracted exposures to a high-LET radiation would result in enhanced frequencies of transformation providing that susceptible cells were cycling or could be induced to cycle. The model explained data on lung tumour induction in rats breathing radon at different concentrations, and uranium miners working in atmospheres containing different concentrations of radon. The model also explains the anomalous finding that lung cancer deaths are often sublinearly correlated with indoor radon concentration. PMID- 7983463 TI - Comparison-based learning: effects of comparing instances during category learning. AB - When learning about a category, people often compare new instances with similar old instances and notice features common to the compared instances. Five experiments demonstrate that such comparisons cause features common to compared instances to be considered more important for the category than equally frequent features that are not common to compared instances. Experiment 1 shows that what is learned depends on which instances are compared. Experiment 2 investigates the conditions under which comparison-based learning occurs. The next experiments find that these comparisons affect subjective feature frequency (Experiment 3) and sensitivity to feature correlations (Experiment 4). Experiment 5 shows that comparisons during early learning affect what is learned from later instances. The discussion focuses on the implications for models of category representation. PMID- 7983462 TI - Ratio versus difference comparators in choice. AB - Several theories in the learning literature describe decision rules for performance utilizing ratios and differences. The present paper analyzes rules for choice based on either delays to food, immediacies (the inverse of delays), or rates of food, combined factorially with a ratio or difference comparator. An experiment using the time-left procedure (Gibbon & Church, 1981) is reported with motivational differentials induced by unequal reinforcement durations. The preference results were compatible with a ratio-comparator decision rule, but not with decision rules based on differences. Differential reinforcement amounts were functionally equivalent to changes in delays to food. Under biased reinforcement, overall food rate was increased, but variance in preference was increased or decreased depending on which alternative was favored. This is a Weber law finding that is compatible with multiplicative, scalar sources of variance but incompatible with pacemaker rate changes proportional to food presentation rate. PMID- 7983464 TI - Models of the effects of prior knowledge on category learning. AB - When people learn about a new category, they are influenced by prior knowledge of other categories. In 5 experiments, subjects made categorization judgments after observing descriptions of persons from a location referred to as City W. In these experiments, prior knowledge as well as observations within City W were manipulated. The integration, weighting, and distortion models of categorization explain prior knowledge effects in different ways. The integration model, which assumes that categorization is influenced by prior examples from other categories, predicted the results of the experiments. It was found that the effect of prior knowledge was independent of the observed proportion of category membership in City W, that the prior knowledge effect was diminished with more observations, and that learning about City W affected subjects' judgments about the general population. The weighting and distortion models could not account for all of the results. PMID- 7983465 TI - Role of an abstract order schema in conceptual judgment. AB - Ss performed same-different judgments for which order information was logically irrelevant. In Experiments 1 and 2, the stimuli for the judgment task were derived from an ordered set of concepts from long-term memory (U.S. presidents ordered on the dimension of historical time); in Experiments 3 and 4 the stimuli were derived from two ordered sets of concepts. In the stimulus set for each experiment, there were several associate phrases for each concept and the task was to judge whether the phrases were paired with the same concept (Experiments 1, 2, and 3) or the same ordering (Experiment 4). The time to respond "different" decreased with the ordinal distance between the concepts even when the concepts belonged to different orderings. It is concluded that same-different judgments are based in part on amodal order information (i.e., not tied to any particular dimension). Two models of the implicated order schema are proposed and tested. PMID- 7983466 TI - Acquisition of procedural skills from examples. AB - Three experiments were run in which Ss first memorized examples of input-output pairs and then generated the outputs for a series of new inputs by analogy to the original examples. Ss first performed these mappings by explicit analogy to an example, but with practice they learned to make these input-output mappings directly without reference to the examples. Ss sped up as a power function of practice over a day (Experiment 1) or days (Experiments 2 and 3). Ss developed a directional asymmetry such that they were slower to calculate the input from the output than the output from the input (whereas initially they had not been). Ss showed similar speed up in their ability to recall the original examples but did not show the same directional asymmetry. Initially, there was some transfer from practicing the procedure to recalling the examples, but this diminished over days. PMID- 7983467 TI - Receiver-operating characteristics in recognition memory: evidence for a dual process model. AB - Evidence is presented that recognition judgments are based on an assessment of familiarity, as is described by signal detection theory, but that a separate recollection process also contributes to performance. In 3 receiver-operating characteristics (ROC) experiments, the process dissociation procedure was used to examine the contribution of these processes to recognition memory. In Experiments 1 and 2, reducing the length of the study list increased the intercept (d') but decreased the slope of the ROC and increased the probability of recollection but left familiarity relatively unaffected. In Experiment 3, increasing study time increased the intercept but left the slope of the ROC unaffected and increased both recollection and familiarity. In all 3 experiments, judgments based on familiarity produced a symmetrical ROC (slope = 1), but recollection introduced a skew such that the slope of the ROC decreased. PMID- 7983468 TI - Serial position effects in implicit and explicit tests of memory. AB - The effects of serial position at study on implicit and explicit tests of memory were investigated. Both primary and recency effects were observed in implicit tests of word-stem completion. These effects, however, were transient. No serial position effects were found in the second half of testing (Experiments 1 and 3) or when testing followed a 1-min, filled delay (Experiment 2). Serial position effects were also examined in explicit tests of cued recall. When performance on explicit cued recall was below ceiling levels, a primacy effect persisted throughout testing (Experiment 3). Similarly, in explicit tests of free recall, primacy effects were consistently observed, both with immediate testing (Experiments 1 and 3) and when testing followed a filled delay (Experiment 2). PMID- 7983469 TI - Effects of imagery on perceptual implicit memory tests. AB - Four experiments demonstrate that imagery can promote priming on perceptual implicit memory tests. When Ss were given words during a study phase and asked to form mental images of corresponding pictures, more priming was obtained on a picture fragment identification test than from a study condition in which Ss performed semantic analyses of words. Imaginal priming of picture fragment identification occurred for recoverable fragments, but not for nonrecoverable fragments. The imagery effect was restricted to the imaged type of material: Imagining pictures (when presented with words) enhanced priming on a picture fragment identification test but not on word fragment completion. Similarly, when pictures were presented, imagining the corresponding words increased priming on word fragment completion but not on picture fragment identification. Overall, results support the hypothesis that imagining engages some of the same mechanisms used in perception and thereby produces priming. PMID- 7983470 TI - Category-order effects in memory span. AB - When Ss are required to recall lists containing both words and digits, memory span is higher when the digits precede the words than when the words precede the digits. In Experiment 1, both forward and backward recall were tested; it was demonstrated that this category-order effect reflects the input position, and not the output position, of the items. Experiment 2 revealed that this effect was not eliminated by a filled retention interval. Experiment 3 showed that the effect was eliminated when lists were presented at a fast presentation rate. In Experiment 4, the effect was eliminated when Ss engaged in articulatory suppression. A 5th experiment extended the findings of Experiment 4 to the case in which lists are composed of semantically related or unrelated words. These results suggest that category-order effects reflect mnemonic activity that Ss engage in during list presentation and do not arise from structural characteristics of the memory system. PMID- 7983471 TI - Extending the irrelevant speech effect beyond serial recall. AB - The irrelevant speech effect is the impairment of immediate memory by the presentation of to-be-ignored speech stimuli. The irrelevant speech effect has been limited to serial recall, but this series of 8 experiments demonstrates that it is considerably more general. Experiments 1-3 show that (a) irrelevant speech inhibits free recall more than does white noise, (b) irrelevant speech impairs free recall even when the speech occurs after the to-be-recalled items, and (c) free recall is inhibited even when the speech is meaningless. Experiment 4 failed to find an effect in free recall with 16-item lists. Experiments 5A-5C extend the effect to recognition of 8-, 12-, and 16-item lists, with both phonologically related and phonologically unrelated lure items. Experiment 6 extends the effect to a cued recall task that discourages the use of serial rehearsal of the to-be remembered items. PMID- 7983472 TI - Time-course studies of reality monitoring and recognition. AB - Two studies used a response-signal procedure to explore the time course of source monitoring judgments about perceived and imagined events. Ss judged whether probe words corresponded to pictures that had previously been seen or imagined or were new. Old-new recognition accuracy grew to significant levels before reality monitoring accuracy, supporting the notion that source monitoring requires more of or a different type of information than does old-new recognition. Also, source identification accuracy developed more quickly for imagined items than for perceived items. This difference in time-course functions is consistent with the idea that memories for perceived and imagined events differ in the relative amounts of various types of information they include (Johnson & Raye, 1981) and that these different types of information may revive or become available to source attribution mechanisms at different rates or may be differentially salient during reality monitoring. PMID- 7983473 TI - Aging associations: influence of speed on adult age differences in associative learning. AB - Two studies, involving a total of nearly 500 Ss, were conducted to determine the mechanisms by which processing speed contributes to the relations between adult age and associative learning. Results of both studies indicated that increased age was related to poorer associative learning largely because of a failure to retain information about previously correct responses. This in turn was related to the effectiveness of encoding briefly presented information in an associative memory task, which was related to measures of processing speed. It is therefore suggested that age-related decreases in speed of processing lead to less effective encoding or elaboration, which results in a fragile representation that is easily disrupted by subsequent processing. PMID- 7983474 TI - Fragmentary knowledge and the processing-specific control of structural sensitivity. AB - Perruchet (1994) suggested that "neither a specific-item retrieval process nor abstractive capacity" is required to explain Vokey and Brooks (1992) results, which instead can be accounted for in terms of knowledge of item fragments. The literature contains 2 definitions of abstractive. Rejecting abstractive in the sense of nonliteral units requires rejecting the results of studies on changed letter transfer, some of which do not need the control group Perruchet claims and thus stand, confirming nonliteral (relational) abstraction. However, the rejection of pooled across items abstraction even in the form of our proposed retrieval-time pooling is feasible, which we had not previously appreciated. Perruchet's rejection of item retrieval ignores Vokey and Brooks' coding and retrieval variations. The coding and retrieval results cannot be ignored simply because they are nonstandard, however. Integrating this literature with known memory phenomena requires incorporating these processing factors, rather than assuming fixed, literal fragments. PMID- 7983475 TI - Astrocyte associations with nodes of Ranvier: ultrastructural analysis of HRP filled astrocytes in the mouse optic nerve. AB - Astrocytes are implicated in the function of nodes of Ranvier because their perinodal processes form contacts with the axonal membrane at nodes. We have filled astrocytes iontophoretically with horseradish peroxidase in the intact mouse optic nerve to resolve the precise relationship between perinodal processes and astrocyte three dimensional structure. We confirm that nodal contacts were formed either by single processes which almost completely enveloped nodes, or by delicate, finger-like projections from larger processes which made discrete nodal contacts. A single perinodal process can form multiple contacts with a node and nodes were contacted by processes from more than one astrocyte. Perinodal processes emanated from larger processes, which terminated as end-feet on blood vessels and at the pia, as well as collateral branches which subsequently ended at nodes; these latter may specifically subserve nodes. Perinodal contacts were also formed directly by the soma and cytoplasmic expansions of the cell body. Both primary processes and collateral branches formed multiple associations with nodes which often appeared in clusters. Thus, all astrocytes formed multiple contacts with nodes, blood vessels and the subpial glia limitans. We conclude that perinodal processes are not formed by a specialized astrocyte in the mouse optic nerve. PMID- 7983476 TI - Effects of cycloheximide on the structural organization of the nucleolus and the coiled body in normal and stimulated supraoptic neurons of the rat. AB - This study was designed to determine the effects of cycloheximide, a protein synthesis inhibitor that interferes with rRNA synthesis and processing, on the nucleoli and coiled bodies of supraoptic nucleus neurons from normally-hydrated and osmotically-stimulated rats. The number of nucleoli and the nucleolar size were estimated on smear preparations of previously silver-impregnated supraoptic nucleus. No significant differences were registered in the mean number of nucleoli per cell in cycloheximide-treated rats. The number of nucleoli per neuron remained constant, at about 1.3, in all animal groups, suggesting that the nucleoli number is strictly regulated in differentiated neurons. By contrast, a significant reduction in the average nucleolar volume of supraoptic nucleus neurons was detected in cycloheximide-treated groups of rats in comparison with their equivalent non-treated groups. By electron microscopy, most nucleoli and coiled bodies of supraoptic nucleus neurons exhibited cycloheximide-induced alterations in their fine structure and configuration. Nucleolar changes included the occurrence of a few large fibrillar centres, the formation of microspherules and small intranucleolar vacuoles or dilated interstices, and the partial segregation of nucleolar components coupled with the transformation of reticulated nucleoli--a nucleolar configuration characteristic of supraoptic nucleus neurons of non-cycloheximide-treated rats--into compact ones. The redistribution of nucleolar components might reflect the interference with rDNA transcription, and also supports the hypothesis that the normal assembly of these components into the nucleolus depends upon ongoing nucleolar transcription. Concerning coiled bodies, most of them revealed ultrastructural alterations, particularly segregation of the amorphous matrix, compactation of coiled threads and formation of coiled body-derived dense bodies of fibrillar nature. Moreover, cycloheximide also induced the formation of smaller dense bodies--here referred to as dense microbodies--which presumably represent a distinct nuclear entity different from coiled bodies. Ultrastructural silver staining of nuclear bodies showed a selective silver reaction on the dense fibrillar component of normal and altered coiled bodies, as well as on the dense microbodies. The possible relationship between the nucleolus and both coiled bodies and dense microbodies is discussed. PMID- 7983477 TI - Update of STA 1992: the anesthesia workstation. PMID- 7983478 TI - Critical issues relating standards for technology to patient safety. The Committee on Technology, Anesthesia Patient Safety Foundation. PMID- 7983479 TI - Anesthesia workstation for 2010. PMID- 7983480 TI - The radical dude. PMID- 7983481 TI - Anesthesia "R" Us, Inc. PMID- 7983483 TI - Design of a workstation: a team summary. PMID- 7983482 TI - The FAS 2000. PMID- 7983484 TI - Designing the workstation for the immediate future. PMID- 7983485 TI - Proposal for a less cumbersome anesthesia workstation. PMID- 7983487 TI - The anesthesia workstation with autopilot design. PMID- 7983486 TI - A new anesthesia workstation design. PMID- 7983488 TI - Design of the four-component anesthesia workstation. PMID- 7983489 TI - The gas busters anesthesia workstation. PMID- 7983490 TI - Designing a unique workstation: the system is the solution. PMID- 7983491 TI - The anesthesia workstation of the future. AB - This team's concern is that technology is not the primary limitation to developing the anesthesia workstation to its full potential. In some ways, medical equipment lags far behind other industries in technological sophistication, standardization, miniaturization, and human factors engineering. Real obstacles appear to be economic and conceptual. The anesthetic process has not been reduced to a series of rigorously derived equations; what the user does is still poorly understood. Manufacturers whose design engineers do not spend a significant part of their work week in the operating room seem to be so ignorant of the real needs of the clinician that their products are doomed to fail or to be mediocre. Clinicians need to encourage their industrial counterparts in the development process to become partners in developing the anesthesia systems of the future. Progress can only be made by having clinicians and developers spend time with one another. Can this inconvenient and frustrating process possibly be worse than the everyday torment caused by manufacturers building what the clinicians do not need, because the clinicians cannot tell them? PMID- 7983492 TI - Designing the workstation: an innovative concept. PMID- 7983493 TI - The M-15: a truly different workstation. PMID- 7983494 TI - Holographic anesthesia lifeguard. PMID- 7983495 TI - Physiological model solving using TK solver, an equation-solving software package. PMID- 7983496 TI - Genetic and molecular R-plasmid analysis of Enterobacteriaceae hospital strains at Children's Hospitals of the former USSR. AB - R-plasmids from Enterobacteriaceae clinical strains, mainly Klebsiella and Serratia, isolated at different neonatal and children's hospitals of different cities of the former USSR for 10 years, were studied for their possible influence on the bacterial host phenotype. Hospital R-plasmids of stable inheritance persisted in hospitals from 2 to 7 years and were disseminated among strains of different genera (Klebsiella, Serratia, Enterobacter) and among different units. The data showed a possibility of long-term molecular rearrangements of R-plasmids in the hospital settings and an acquisition of genetic determinants encoding enterotoxin production. A novel R-plasmid encoding cytotoxicity to HEp-2 cells involved in two nosocomial outbreaks due to K. pneumoniae strains was reported. K. pneumoniae population heterogeneity was evaluated by using the plasmid parameters of strains. Their heterogeneity of a bacterial population was significantly lower during nosocomial outbreaks than in interepidemic periods. PMID- 7983497 TI - Effect of the inoculum size on susceptibility tests performed on sessily growing bacteria. AB - It has been clearly established that the inoculum size greatly affects the results of antibiotic susceptibility tests performed in both liquid and solid media in standard laboratory growth conditions (i.e. planktonic). Recently methods were developed to perform antibiotic susceptibility tests on bacteria growing in sessile conditions. The present study investigates the effect of the inoculum size on results obtained by these methods. Results show that the inoculum size does not affect tests performed in sessile conditions. A simple and reliable method is proposed to be applied to routine microbiological laboratory procedures. PMID- 7983498 TI - Escherichia coli: effect of fosfomycin trometamol on some urovirulence factors. AB - The aim of our study was to evaluate the interference of fosfomycin trometanol (F.T.), at subinhibitory concentrations (1/4 and 1/8 MICs), on some urovirulence factors of Escherichia coli (12 strains). We tested fimbriae production, adhesion to uroepithelial cells, hydrophobicity, motility and hemolysin production of E. coli grown in the presence or absence of F.T. The strains tested, grown in the presence of F.T. (1/8 MIC), were less capable of adhering to uroepithelial cells, had less hemagglutination and reduced motility. This behavior was enhanced at 1/4 MIC of F.T. The hemolysin production and hydrophobicity properties present in some of our tested strains also were significantly decreased when the E. coli were grown in the presence of sub-MIC concentrations of F.T. These results suggest that F.T. may be of clinical use as treatment for acute urinary tract infection and in pyelonephritis prophylaxis. PMID- 7983499 TI - Comparison of broth dilution and semisolid agar dilution for in vitro susceptibility testing of Cryptococcus neoformans. AB - We compared the in vitro activity of amphotericin B, flucytosine, itraconazole, fluconazole, ketoconazole and miconazole against 18 strains of Cryptococcus neoformans by using two methods: microbroth dilution and semisolid agar dilution. By both of the methods minimum inhibitory concentrations (MICs) showed a wide range for all antifungal agents but not for amphotericin B. Statistically significant differences between the two methods were observed only with amphotericin B and flucytosine, p = 0.048 and p = 0.045 respectively. Our study suggests that azole susceptibility testing for C. neoformans may be performed by the broth microdilution as well as the semisolid agar test. The choice of the method when testing amphotericin B and flucytosine is more problematic. PMID- 7983500 TI - Effect of ceftriaxone on the phagocytosis and intracellular killing of Staphylococcus aureus by human macrophages. AB - The efficacy of an antimicrobial agent in the treatment of infections depends upon the interactions of bacteria, antibiotic and phagocytes. The influence of ceftriaxone on the phagocytic and bactericidal activity of human macrophages in vitro and ex vivo was investigated. At concentrations one-half the minimum inhibitory concentration (1/2 x MIC) the antibiotic caused in vitro a significant enhancement of phagocytosis and a reduction in the survival of intracellular Staphylococcus aureus. The distinction between any effect of ceftriaxone on the staphylococci and the macrophages was made by exposure of each of them to the antibiotic before they were incubated together. The results suggest that ceftriaxone may have a direct positive action on macrophages, possibly by interfering with the cellular membrane functions and hence enhancing engulfment of bacteria. The ex vivo data seem to corroborate this hypothesis. PMID- 7983501 TI - Phage F-116 transduction of antibiotic resistance from a clinical isolate of Pseudomonas aeruginosa. AB - The lysate of phage F-116, propagated in a multiple drug resistant clinical isolate of Pseudomonas aeruginosa No. 131 was used to transduce determinants of antibiotic resistance to susceptible auxotrophic laboratory strains of the same species. The phage preparation, designated F-116/131 was found to transduce four determinants of resistance, i.e. to imipenem, cefotaxime, kanamycin and carbenicillin, but not to streptomycin, gentamicin, ceftazidime nor ciprofloxacin/ofloxacin. No conjugal transfer of any resistance determinants could be demonstrated in mating experiments using strain No. 131 and two rifampicin-resistant strains of P. aeruginosa which were highly susceptible to all antibiotics studied. These results might suggest that transduction could be an additional way to conjugational transfer of antibiotic resistance among P. aeruginosa. PMID- 7983502 TI - Control of the body burden of M. avium complex is associated with improved quality of life and prolonged survival of patients with AIDS: a prospective trial with rifabutin combined with isoniazid, clofazimine, ethambutol. AB - The objectives of this study were to assess whether culture conversion affects quality of life (QoL), survival and Mycobacterium avium complex (MAC)-associated morbidity in patients with AIDS. Data from an open, multicenter, noncomparative trial were analyzed to test the benefit of suppressing mycobacteria: measures of QoL, clinical outcomes and quality-adjusted survival are compared on occasion of culture-negative and positive assessments. The study was conducted at AIDS clinics in France, coordinated by the GETIM, with the participation of 51 AIDS patients with culture-proven Non-Tuberculous Mycobacteria (NTM) disease. Patients underwent a quadruple drug-regimen. The following parameters were investigated: (i) Culture conversion to a negative finding (= suppression) or on > 2 occasions, including each patient's last valid observation (= conversion); (ii) survival after treatment start; (iii) QoL by using the ECOG score, re-coded 0 to 4 for worst to best performance status; (iv) quality-adjusted survival. On treatment, > 1 negative culture was recorded for 69% of the evaluable patients, corresponding to 111 person-months of observation. Positive culture findings accounted for 42 person-months only. Patients' performance status (mean 1.8 at entry) worsened or improved according to whether culture was positive or negative (means 1.2 and 2.2; total scores 109 and 217 person-months, respectively). Similarly, MAC attributable morbidity was significantly reduced when culture was negative. Mean survival was 195 days longer in treatment success patients. These analyses suggest that, in patients with NTM disease occurring as a late complication of AIDS, treatment was effective in improving clinical status and survival, and in suppressing bacterial growth.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7983503 TI - Piperacillin/tazobactam in the treatment of lower respiratory tract infections: an open non-comparative and multicentered trial. Latin American Clinical Research Group. AB - The aim of this study was to determine the clinical and bacteriological efficacy and safety of piperacillin-tazobactam (PT) (4g/500 mg IV tid) in the treatment of 107 adult patients with lower respiratory tract infections (LRTI) requiring hospitalization. Patients included were 66 men and 41 women with a mean age of 55.2 years (range 18-89), enrolled from Mexican (6) and Argentinean (5) hospitals. Ninety-nine clinically evaluable patients (92.5%), 87 with pneumonia and 12 with bronchitis, were treated for a mean period of 9.3 and 7.3 days, respectively. Response to treatment was favorable in 94.3% cases with pneumonia and 100% of cases with bronchitis; 86 cases (80.3%) were bacteriologically evaluable, 77 with pneumonia (eradication 74, persistence 1, superinfection 2), and 9 with bronchitis (eradication in all). Streptococcus pneumoniae was recovered in 24, Klebsiella pneumoniae in 21, Staphylococcus aureus in 8, Haemophilus influenzae in 7, Pseudomonas aeruginosa in 5, Enterobacter spp. in 6, Escherichia coli in 6 and other organisms in 12. Toxicity or intolerance were not observed. Our data suggest that PT is a reliable therapy for severe LRTI. PMID- 7983504 TI - Prognostic significance of serum lactate dehydrogenase in patients with osteosarcoma of the extremities. AB - Six hundred and fifty-six patients with osteosarcoma of the extremities (107 metastatic and 549 with localized disease) were followed from 2.5 to 20 years (average: 10 years) to evaluate whether their pretreatment serum lactate dehydrogenase (LDH) enzyme levels had a clinical value in predicting the course of the disease. The percentage of patients who had an elevated serum LDH at the time of diagnosis was significantly higher in those patients with metastatic disease than those who had localized disease (64% versus 33%, p < 0.0001). For those who presented with localized disease and had an increased serum LDH level, far more ultimately developed a relapse of disease (60% versus 38%, p < 0.0001) than those patients with a normal pre-treatment value. The prognostic significance of the serum LDH was more pronounced for the 247 patients treated with adjuvant chemotherapy (relapse rate of 72% versus 48%; p < 0.0002) than the 271 patients treated with neoadjuvant chemotherapy (relapse rate: 46% versus 28%, p < 0.005). Following treatment, serum LDH levels almost uniformly returned to normal and no correlation between postoperative levels and relapse of disease could be identified. We have demonstrated that in patients with osteosarcoma of the extremities, pretreatment serum LDH levels have a definite prognostic value which should be considered when comparing the results achieved with different therapeutic protocols and in planning new randomized clinical trials. PMID- 7983505 TI - Etoposide, doxorubicin and cisplatin (EAP regimen) in advanced gastric cancer. AB - The treatment of advanced gastric cancer is unsatisfactory. The response rates for single chemotherapy agents: 5-fluorouracil, mitomycin-c, methotrexate, cisplatin, adriamycin, nitrosoureas and etoposide are approximately 10-25% and response duration ranges from 3 to 6 months. Complete responses with single agents are rare. Combination chemotherapy produces higher response rates, but these responses are short. Recently the combination of etoposide, adriamycin and cisplatin (EAP regimen) has been reported to produce results superior to what have been previously reported with other regimens. Twenty-four consecutive patients with locally advanced or metastatic gastric cancer (stage III-IV) were treated between June 1990 and December 1992 with the EAP regimen at our Department. Twenty-two patients were evaluable for response and toxicity. Objective responses were observed in 8 of 22 patients (response rate 36%; 95% confidence interval 17% to 59%). No clinical complete response was found. The median duration of the response was 7 months (range 2 to 22). Myelosuppression represented the primary toxicity associated with the EAP regimen. Grade 4 leukopenia was observed in 4 patients (18%). Grade 3-4 thrombocytopenia was registered in two patients, and grade 3 anemia was detected in 4 patients (18%). The median survival for all patients was 8 months and 12 months for the 8 responding patients. The EAP regimen seems to be an effective chemotherapeutic regimen, but cannot be considered the standard therapy for patients with locally advanced or metastatic gastric cancer, because of the high incidence of moderate to severe myelotoxicity and a response rate and duration of survival similar, but not superior, to those obtained using a less toxic schedule. PMID- 7983506 TI - Voltage-activated potassium currents in isolated motor neurons from the jellyfish Polyorchis penicillatus. AB - 1. We describe two voltage-activated potassium currents in the swim motor neurons (SMNs) of the hydrozoan jellyfish, Polyorchis penicillatus. Recordings from neurons isolated in primary cultures were made using the tight-seal, whole-cell technique. 2. One current, IK-fast, turned on rapidly (time to peak = 6-15 ms), was half-activated at -10 to 0 mV, decayed with two exponential phases (tau were approximately 70 ms and approximately 1 s), and was half-inactivated by prepulses around -53 mV. It likely plays an important role in regulating the duration of SMN action potentials. IK-fast has features shared by delayed rectifiers and A like currents in other invertebrates and vertebrates. 3. Another current, IK slow, elicited from a holding potential of -30 mV, exhibited a slow onset (tau = 65-250 ms), was half-activated approximately +24 mV, exhibited a shallower voltage dependence than IK-fast, and did not inactivate. It was slower than most known delayed rectifiers. PMID- 7983507 TI - Covert attention suppresses neuronal responses in area 7a of the posterior parietal cortex. AB - 1. The effect of covert attention was studied in area 7a of the posterior parietal cortex of rhesus monkeys performing a spatial match-to-sample task. The task required the animals to fixate a central target light, to detect and remember the location of a transient spatial cue, and to respond when one of a series of stimuli appeared at the cued location. Neuronal responses evoked by the visual stimuli were recorded during each behavioral trial. 2. Thirty-eight percent of the neurons isolated and studied in these experiments responded to visual stimuli. The responses of 55% of the neurons tested were suppressed, and 5% enhanced for stimuli presented at the attended location. Responses in the remaining neurons (40%) were unaffected by shifts in attention. 3. Activity in 57% of the suppressed neurons was reduced to rates not significantly different from spontaneous activity. 4. The extent of suppression for individual neurons was often restricted to the attended portion of the receptive field. 5. These data suggest a potential role for these neurons in the redirection of visual attention. PMID- 7983508 TI - Importance of unpredictability for reward responses in primate dopamine neurons. AB - 1. We used single neuron recording techniques in two behaving monkeys to investigate the conditions in which dopamine neurons respond to primary rewarding or potentially rewarding stimuli. Animals received drops of liquid either outside behavioral tasks or as rewards during learning or established performance of an auditory reaction time task. 2. Three quarters of dopamine neurons showed a short latency, phasic response to liquid that was delivered outside the task without being predicted by phasic stimuli. The same neurons responded to liquid reward during learning but not when task performance was established, at which time the neuronal response occurred to the conditioned, reward-predicting, movement triggering stimulus. 3. These data suggest that the responses of dopamine neurons to rewarding or potentially rewarding liquid are due to the temporally unpredicted stimulus occurrence. A known, reward-predicting, tonic context does not prevent dopamine neurons from responding to the rewarding liquid. The responses during learning apparently occur because reward is not yet reliably predicted by a conditioned phasic stimulus. Because the unpredicted occurrence of reward is of central importance for learning, these responses allow dopamine neurons to play an important role in reward-driven learning. PMID- 7983509 TI - Extraocular muscle proprioception functions in the control of ocular alignment and eye movement conjugacy. AB - 1. The function of extraocular muscle proprioception in the control of eye movements is uncertain. We tested the hypothesis that proprioception contributes to the long-term regulation of ocular alignment and eye movement conjugacy. 2. Eye movements were recorded in monkeys with unilateral extraocular muscle palsies, before and after proprioceptive deafferentation of the paretic eye. Following deafferentation, ocular alignment and saccade conjugacy gradually worsened over several weeks. In contrast, disconjugate adaptation induced by habitual binocular viewing with a prism (disparity-mediated adaptation) occurred normally after deafferentation. 3. These results provide the first evidence that proprioception functions in the control of eye movements in primates, and indicate that proprioception contributes to the long-term adaptive mechanisms that regulate ocular alignment during fixation and saccades. The error signal used in this process may be derived from a mismatch between the efference copy and proprioceptive afference. PMID- 7983510 TI - Altered desensitization produces enhancement of EPSPs in neocortical neurons. AB - 1. Neocortical brain slices were prepared from rats (35-50 days of age) and maintained in vitro. Intracellular recordings were obtained from neurons in cortical layers II/III. The effect of bath application of cyclothiazide (CYZ), a potent blocker of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) receptor desensitization, on evoked synaptic activity and passive membrane properties was investigated. 2. Bath application of CYZ did not significantly affect resting membrane potential, input resistance, or repetitive firing. CYZ increased both the amplitude and duration of evoked excitatory postsynaptic potentials (EPSPs). Polysynaptic responses were also augumented. These effects persisted after the blockade of N-methyl-D-aspartate (NMDA) receptors with D-2 amino-5-phosphonovaleric acid (D-APV). The magnitude of these effects appeared to vary directly with stimulation intensity and presumably, amount of glutamate release. 3. Epileptiform activity was induced by bath application of bicuculline methiodide. The amplitude and duration of evoked paroxysmal discharges were increased by CYZ. Similar results were seen in presence of D-APV. 4. These results indicate that CYZ has significant effects on synaptic transmission. Desensitization of non-NMDA receptors may be an important mechanism for determining the time course of EPSPs and in curtailing epileptiform responses in the rat neocortex. PMID- 7983511 TI - Physiologically silent sodium channels in mammalian outer hair cells. AB - 1. Voltage-dependent properties of isolated guinea pig outer hair cells (OHCs) were investigated using whole-cell recording. An inward current was detected in approximately 10% of the cells. This inward current was identified as belonging to the voltage-activated sodium current family on the basis of its high sensitivity to tetrodotoxin and the effect of substitution of impermeant ions. Although this is the first report of a sodium current in the mammalian cochlea, it differs from the classical neuronal sodium current by having a variable magnitude from cell to cell and an inactivation that is shifted to hyperpolarized potentials. The sensory processing role of hair cells in general and outer hair cells in particular could be disrupted by the presence of a regenerative voltage dependent current. The functional role of the OHC sodium channels is puzzling, particularly as they may be silent in vivo. PMID- 7983512 TI - Sensory transduction of head velocity and acceleration in the toadfish horizontal semicircular canal. AB - 1. Sinusoidal mechanical indentation of the long-and-slender limb of the horizontal semicircular canal and/or utricle was used to produce adequate stimulation of the labyrinth. Indentation of the canal increased, while indentation of the utricle decreased the afferent discharge rate. This follows because indentation of the canal and utricle produce oppositely directed mechanical stimuli as defined by endolymph flow, transcupular pressure, and cupular deflection. Simultaneous in-phase indentations of both the canal and utricle, with amplitudes adjusted to produce equal (but opposite) magnitudes of afferent response modulation, generate destructive interaction that minimizes the afferent modulation, whereas sinusoidal indentation 180 degrees out-of-phase generates constructive interaction that maximizes the afferent modulation. This observation correlates directly with analysis of the labyrinthine elasto hydrodynamics which predicts that balanced in-phase indentations minimize macromechanical endolymph flow through the ampullary cross section and maximize the dilatational pressure within the ampulla acting equally on both sides of the cupula and across the labyrinthine wall. 2. Two groups of afferents are identified according to their response to balanced sinusoidal indentation of the canal limb and the utricle. In one group there is complete destructive interaction and the afferent response can be effectively nulled by adjusting the relative amplitude and phase of the two stimuli. In the second group a residual afferent response remains that cannot be nulled. The residual is described in the model as unit-specific sensitivity to dilatational pressure acting equally on both sides of the cupula. PMID- 7983513 TI - Cerebellar control of postural scaling and central set in stance. AB - 1. The effects of cerebellar deficits in humans on scaling the magnitude of automatic postural responses based on sensory feedback and on predictive central set was investigated. Electromyographic (EMG) and surface reactive torques were compared in patients with anterior lobe cerebellar disorders and in normal healthy adults exposed to blocks of four velocities and five amplitudes of surface translations during stance. Correlations between the earliest postural responses (integrated EMG and initial rate of change of torque) and translation velocity provided a measure of postural magnitude scaling using sensory information from the current displacement. Correlations of responses with translation amplitude provided a measure of scaling dependent on predictive central set based on sequential experience with previous like displacements because the earliest postural responses occurred before completion of the displacements and because scaling to displacement amplitude disappeared when amplitudes were randomized in normal subjects. 2. Responses of cerebellar patients to forward body sway induced by backward surface displacements were hypermetric, that is, surface-reactive torque responses were two to three times larger than normal with longer muscle bursts resulting in overshooting of initial posture. Despite this postural hypermetria, the absolute and relative latencies of agonist muscle bursts at the ankle, knee, and hip were normal in cerebellar patients. 3. Although they were hypermetric, the earliest postural responses of cerebellar patients were scaled normally to platform displacement velocities using somatosensory feedback. Cerebellar patients, however, were unable to scale initial postural response magnitude to expected displacement amplitudes based on prior experience using central set. Randomization of displacement amplitudes eliminated the set effect of amplitude on initial responses in normal subjects, but responses to randomized and blocked trials were not different in cerebellar patients. 4. Cerebellar patients compensated for hypermetric responses and lack of anticipatory scaling of earliest gastrocnemius activity by scaling large, reciprocally activated tibialis and quadriceps antagonist activity with the displacement velocity and amplitude. Correlations between these antagonist EMG integrals and displacement amplitudes were preserved when amplitudes were randomized, suggesting that feedback-dependent and not set-dependent mechanisms were responsible for scaling of antagonists by cerebellar patients. Antagonist compensation for initial hypermetric responses also could be induced in normals when they overresponded to unexpectedly small amplitudes of surface displacements. 5. The major effects of anterior lobe cerebellar damage on human postural responses involves impairment of response magnitude based on predictive central set and not on use of velocity feedback or on the temporal synergic organization of multijoint postural coordination.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 7983514 TI - The primate subthalamic nucleus. I. Functional properties in intact animals. AB - 1. The present study tests several key aspects of the current model of the intrinsic circuitry of the basal ganglia, in particular the degree to which basal ganglia-thalamocortical circuits are functionally segregated at the level of the subthalamic nucleus (STN). To this end the responses of STN cells to somatosensory examination (n = 301 cells), the polarity and latencies of neuronal responses to passive and active movements (n = 223 cells), responses to microstimulation (n = 1589 sites), and cross-correlation functions of pairs of neighboring neurons (n = 72 pairs) were studied in STNs of three African green monkeys. 2. The activity of 55% of cells examined in STN was briskly modulated in response to passive movements of individual contralateral body parts. Of these, 86% responded to passive joint rotation of muscle palpation, but in some cases (25% of responding cells) responses were also elicited by light touch. In 91% of the responding cells responses were elicited by manipulations around a single joint only. 3. The caudoventral sector in STN was largely devoid of cells with responses to somatosensory stimulation. Within the rostrodorsal zone a lateral region containing neurons that responded to arm movements and a more medial region with neurons responding to leg movement were found. Cells responding to orofacial movements were located more dorsally and rostrally. Neurons with similar responses to active and passive movements of the limbs tended to be clustered within "arm" and "leg" zones. 4. Of identified arm cells in STN (n = 80), 36% responded to the application of torque pulses to the elbow (43 responses overall). Forty-eight percent of these cells responded to both extension and flexion torques. Ninety-three percent of the responses were initial increases in discharge, which characteristically occurred earlier and were shorter than initial decreases. Fifty-three percent of the responses were biphasic or multiphasic. 5. During active step tracking movements 40% of STN arm cells (n = 53 cells) responded with significant changes in activity. Thirty-six percent of these cells showed responses with both extension and flexion movements. Of the responses, 90% were increases in discharge. Only 14% of all responses were biphasic or multiphasic. Responses tended to occur around the time of movement onset (average latency 2 ms after movement onset). 6. Microstimulation (bipolar pulses, 40 microA, 200-500 ms train duration, 400 Hz) of the core of STN itself did not appear to produce movement.4+ synchronized activity in only 11% of pairs.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 7983515 TI - The primate subthalamic nucleus. II. Neuronal activity in the MPTP model of parkinsonism. AB - 1. The neuronal mechanisms underlying the major motor signs of Parkinson's disease were studied in the basal ganglia of parkinsonian monkeys. Three African green monkeys were systemically treated with 1-methyl-4-phenyl-1,2,3,6 tetrahydropyridine (MPTP) until parkinsonian signs, including akinesia, rigidity, and a prominent 4- to 8-Hz tremor, appeared. The activity of neurons in the subthalamic nucleus (STN) and in the internal segment of the globus pallidus (GPi) was recorded before (STN, n = 220 cells; GPi, n = 175 cells) and after MPTP treatment (STN, n = 326 cells; GPi, n = 154 cells). 2. In STN the spontaneous firing rate was significantly increased from 19 +/- 10 (SD) spikes/s before to 26 +/- 15 spikes/s after MPTP treatment. Division of STN neurons recorded after MPTP treatment into cells with rhythmic bursts of discharge occurring at 4-8 Hz (as defined by autocorrelation analysis) and neurons without 4- to 8-Hz periodic activity revealed an even more prominent increase in the firing rate of the 4- to 8-Hz oscillatory neurons. 3. In GPi overall changes in the average firing rate of cells were inconsistent between different animals and behavioral states. However, the average firing rate of the subpopulation of neurons with 4- to 8-Hz periodic oscillatory activity after treatment with MPTP was significantly increased over that of all neurons before MPTP treatment (from 53 to 76 spikes/s, averaged across monkeys). 4. In the normal state the percentage of neurons with burst discharges (as defined by autocorrelation analysis) was 69% and 78% in STN and GPi, respectively. After MPTP treatment the percentage of cells that discharged in bursts was increased to 79% and 89%, respectively. At the same time the average burst duration decreased (from 121 +/- 98 to 81 +/- 99 ms in STN and from 213 +/- 120 to 146 +/- 134 ms in GPi) with no significant change in the average number of spikes per burst. 5. Periodic oscillatory neuronal activity at low frequency, highly correlated with tremor, was detected in a large number of cells in STN and GPi after MPTP treatment (average oscillation frequency 6.0 and 5.1 Hz, respectively). The autocorrelograms of spike trains of these neurons confirm that the periodic oscillatory activity was very stable. The percentage of cells with 4- to 8-Hz periodic activity significantly increased from 2% to 16% in STN and from 0.6% to 25% in GPi with the MPTP treatment.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 7983516 TI - The primate subthalamic nucleus. III. Changes in motor behavior and neuronal activity in the internal pallidum induced by subthalamic inactivation in the MPTP model of parkinsonism. AB - 1. The effects of reversible and irreversible pharmacological manipulations of the neuronal activity in the subthalamic nucleus (STN) on parkinsonian motor signs and neuronal activity in the internal segment of the globus pallidus (GPi) were studied in African green monkeys rendered parkinsonian by treatment with 1 methyl-4-phenyl-1,2,3,6-tetrahydropyridine. 2. Muscimol injections (< or = 1 microliter, 1 microgram/microliter) into STN reduced neuronal activity recorded at the injection site within minutes. This was immediately followed by reduced akinesia, tremor, and rigidity, as well as the emergence of dyskinesias in contralateral limbs. The motor effects were accompanied by generalized behavioral activation, lasted between 10 and 60 min, and were strongly dependent on the site of injection, with injections into the lateral "arm area" of STN first affecting contralateral arm movements and injections into the "leg" area affecting leg movements first. 3. Bicuculline injections (< or = 1 microliter, 1 microgram/microliter) into STN marginally increased the neuronal activity and induced neuronal discharge in bursts. Rigidity, akinesia, and tremor in the contralateral limbs were not changed. 4. Injections of ibotenic acid in two animals (2 and 7 microliters, 10 micrograms/microliters) resulted in 70 and 51% destruction of STN, respectively. Similarly to the muscimol injections, this resulted in a reduction of the neuronal activity, a reversal of parkinsonian motor signs, and the development of dyskinesias in the contralateral limbs. 5. Although tremor was significantly reduced after STN lesions, periodic oscillatory neuronal activity in GPi persisted. The strength of modulation of the neuronal oscillation was not significantly changed after STN lesion. 6. The percentage of cells in GPi exhibiting increases in discharge in response to torque application was significantly reduced after STN lesion. The magnitude and duration of the responses with increase in firing rate were reduced after STN lesioning. 7. These results support the hypothesis that abnormally increased tonic and phasic activity in STN leads to abnormal GPi activity and is a major factor in the development of parkinsonian motor signs. Furthermore they imply that cells in the basal ganglia have the intrinsic property of discharging in periodic bursts, which is unmasked under parkinsonian conditions. PMID- 7983517 TI - Synchronous bursting in a subset of interneurons inhibitory to the goldfish Mauthner cell: synaptic mediation and plasticity. AB - 1. Presynaptic activity in the inhibitory network impinging on the Mauthner (M-) cell was investigated in the goldfish medulla in vivo using extra- and intracellular recordings. The inhibitory presynaptic volley elicited by stimulation of the contralateral vestibular nerve consisted of multiple successive peaks at high frequency (up to 1,000 Hz). Less pronounced multicomponent responses were recorded after antidromic activation of the M-cell. Such high-frequency "oscillatory" field potentials also occurred spontaneously. 2. In intracellular recordings, a subset of inhibitory interneurons showed evoked and spontaneous burst discharge. Burst action potentials were correlated with the peaks in the extracellular volley, suggesting that repetitive firing of these cells is synchronized. Nonbursting cells, on the other hand, fired single action potentials in response to vestibular stimuli and were not activated via the M cell collateral network. 3. Bursting cells were determined morphologically to be part of the feedback inhibitory circuit. Their responses to stimulation of the contralateral vestibular nerve thus suggest the existence of a crossed excitatory pathway to these interneurons. 4. Vestibular-evoked excitatory postsynaptic potentials (EPSPs) in bursting interneurons had a short latency of 0.781 +/- 0.08 ms (mean +/- SD, n = 18) but reached threshold at 2.25 +/- 1 ms (n = 21). These characteristics are suggestive of a chemically mediated EPSP. Indeed, the evoked synchronous repetitive activity of these cells was prevented by superfusion with excitatory amino-acid receptor antagonists. 5. Bursting neurons showed several characteristics that differentiate them from nonbursting cells, including brief action potentials, plateau responses, and intense spontaneous subthreshold activity. 6. With extracellular recordings, tetanization of contralateral vestibular primary afferents evoked a long-lasting potentiation of oscillatory population responses in 11 of 27 cases. Furthermore in three experiments, the frequency of occurrence of spontaneous bursts was enhanced and a similar facilitation was detected at the intracellular level. 7. We conclude that a subset of interneurons in this inhibitory network is capable of repetitive discharges and that evoked as well as spontaneous firing in this population is synchronized. Although electrical coupling between interneurons may mediate synchronization and intrinsic membrane properties may promote burst activity, our data suggest strongly that repetitive firing requires chemically mediated transmission. Furthermore they indicate that the mechanisms underlying evoked as well as spontaneous bursting in this population show activity-dependent plasticity. PMID- 7983518 TI - Somatosensory, multisensory, and task-related neurons in cortical area 7b (PF) of unanesthetized monkeys. AB - 1. The goal of this study was to quantitatively characterize the response properties of somatosensory and multisensory neurons in cortical area 7b (or PF) of monkeys that were behaviorally trained to perform an appetitive tolerance escape task. Particular emphasis was given to characterizing nociceptive thermal responses and correlating such responses to thermal pain tolerance as measured by escape frequency. 2. A total of 244 neurons that responded to somatosensory stimulation alone or to both somatosensory and visual stimulation (multisensory) were isolated and studied in the trigeminal region of cortical area 7b. Thirty neurons responded only to visual stimulation. Thermoreceptive neurons formed approximately 13% (31 of 244) of the neurons that had somatosensory response properties. Thermal nociceptive neurons made up approximately 9% (21 of 244) of the neurons that had somatosensory response properties or approximately 68% (21 of 31) of the neurons that had thermoreceptive response properties. Thermal nociceptive neurons responded either exclusively to noxious thermal stimuli (high threshold thermoreceptive, HTT) or differentially to nonnoxious and noxious thermal stimuli (wide-range thermoreceptive, WRT). Multimodal HTT neurons had nonnociceptive (low-threshold mechanoreceptive, LTM) and/or nociceptive (nociceptive-specific, wide-dynamic-range) mechanical receptive fields, whereas multimodal WRT neurons had only nonnociceptive (LTM) mechanical receptive fields. Thermal nonnociceptive neurons (low-threshold thermoreceptive, LTT) made up approximately 3% (8 of 244) of the neurons that had somatosensory properties or approximately 26% (8 of 31) of the neurons that were thermoreceptive. The background discharge of two thermoreceptive neurons (6%, 2 of 31) was inhibited by innocuous thermal stimulation. 3. Thermal nociceptive neurons (HTT and WRT) were functionally differentiated by statistical analyses into subpopulations that did encode (HTT-EN, WRT-EN) and did not encode (HTT-NE, WRT-NE) the magnitude of noxious thermal stimulus intensities. The mean slopes and median regression coefficients for the stimulus-response (S-R) functions of HTT-EN and WRT-EN neurons, respectively, were significantly greater than those for the S-R functions of HTT-NE and WRT-NE neurons. In contrast to HTT-NE and WRT-NE neurons, HTT-EN and WRT-EN neurons reliably encoded the magnitude of noxious thermal intensity by grading their mean discharge frequency. 4. The S-R functions of HTT EN and WRT-EN neurons, unlike those of HTT-NE and WRT-NE neurons, closely approximated stimulus intensity-escape frequency functions.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 7983519 TI - N-methyl-D-aspartate receptor-mediated voltage oscillations in neurons surrounding the central canal in slices of rat spinal cord. AB - 1. The present study used the whole-cell patch-clamp technique to record from visually identified neurons surrounding the central canal in 300-microns transverse slices of lumbosacral spinal cord from 7- to 14-day-old rats. Neurons in this location are implicated in rhythmical activity during locomotion. We assessed whether similarly located neurons could produce voltage oscillations by local perfusion of neuroactive substances known to initiate locomotor activity. 2. The sample population had mean values for cell resistance and membrane time constant of 1,020 M omega and 61.5 ms, respectively. Three general categories of oscillatory behavior were observed; spontaneous low-frequency voltage oscillations in the absence of an applied agonist, N-methyl-D-aspartate (NMDA) induced rhythmic low-frequency voltage oscillations in the presence of tetrodotoxin (TTX), and NMDA-induced "unpatterned" low-frequency voltage oscillations in TTX. 3. Three of 42 neurons exhibited spontaneous low-frequency voltage oscillations and one continued to oscillate in the presence of TTX. In 34 other neurons, manual adjustments of membrane voltage in 10 mV increments between -60 and -20 mV failed to elicit voltage oscillations (in TTX). 4. Five of 42 neurons produced rhythmic low-frequency voltage oscillations in the presence of TTX during applications of NMDA (20-100 microM). Oscillation frequency ranged from 0.09 to 1.45 Hz. These neurons were located in a similar region, ventrolateral to the central canal. 5. Thirteen of 42 neurons underwent NMDA evoked "unpatterned" low-frequency voltage oscillations (in TTX) characterized by great variability in depolarized and baseline membrane potential durations. Three neurons produced single depolarizing phases only. Oscillation frequency ranged from 0.03 to 0.47 Hz. These neurons were located predominantly in the dorsal region surrounding the central canal with two others located just ventral to the canal. 6. Low-frequency voltage oscillations demonstrated a dependence on voltage, applied agonist, and agonist concentration. Rhythmic and unpatterned oscillatory events typically arose from membrane voltages ranging from -70 to -55 mV with plateau peaks from -40 to -30 mV. Although NMDA (20-100 microns) evoked voltage oscillations in neurons, kainate (10-50 microns), serotonin (10-200 microns), and noradrenaline (50-100 microns) failed to evoke voltage oscillations in all neurons tested, including those where NMDA induced voltage oscillations.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 7983520 TI - Electrophysiological and morphological characteristics of layer VI pyramidal cells in the cat motor cortex. AB - 1. Intracellular recordings were made from layer VI pyramidal cells in in vitro slice preparations of the cat motor cortex (area 4 gamma). Layer VI pyramidal cells were identified morphologically by intracellular injection of biocytin. 2. Of 22 layer VI pyramidal cells examined, single action potentials were followed by depolarizing afterpotentials (DAP) in 9 cells, but were not followed by DAP in the remaining 13 cells. The amplitude of DAP was 3.4 +/- 1.4 mV (mean +/- SD, n = 9) when measured from the negative peak of fast afterhyperpolarization to the peak of DAP. 3. In response to depolarizing current pulses with a duration of 300 400 ms, pyramidal cells showing DAP displayed a train of action potentials in a phasic-tonic pattern without any appreciable adaptation in the tonic firing, whereas pyramidal cells lacking DAP exhibited a weak adaptation after phasic firing. Anomalous rectification was seen in both pyramidal cells showing DAP and those lacking DAP. 4. Repetitive doublet or triplet spiking was induced in DAP showing pyramidal cells in response to a depolarizing current pulse after injecting strong depolarizing current pulses of 400 ms duration at 1 Hz for 30-60 s, but was never induced in DAP-lacking pyramidal cells. Doublet/triplet spiking lasted 5-10 min and returned to the original single spiking. An application of CsCl induced a burst firing in DAP-showing pyramidal cells. 5. In the nine pyramidal cells showing DAP, seven cells had shorter apical dendrites that arborized extensively at layer V and terminated in the middle part of layer III. In the 13 pyramidal cells lacking DAP, 11 cells had longer apical dendrites that arborized less frequently and extended into layer II or I. Main axons could be traced into the deep white matter in 17 of the 22 layer VI pyramidal cells examined. 6. Ascending recurrent axon collaterals were more prominent in pyramidal cells with longer apical dendrites than in pyramidal cells with shorter apical dendrites. The terminal bouton-like swelling observed along the recurrent axon collaterals arising from the pyramidal cells with longer apical dendrite were distributed most densely at the level between the bottom part of layer III and the top part of layer V. In contrast, those arising from the pyramidal cells with shorter apical dendrite were distributed mainly at the levels of layers V and VI.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 7983521 TI - The reticulospinal glutamate synapse in lamprey: plasticity and presynaptic variability. AB - 1. The glutamatergic synapses formed between the unbranched giant reticulospinal axons onto spinal neurons in lamprey offer a central vertebrate synapse in which the presynaptic element can be impaled with one or several microelectrodes, which may be used for recording as well as microinjection of different substances. To provide a basis for the use of this synapse in studies of release mechanisms, we have examined the use-dependent modulation of the synaptic response under conditions of conventional cell body stimulation, and during direct stimulation of the presynaptic axon. 2. To examine the stability of the mixed electrotonic and chemical reticulospinal excitatory postsynaptic potential (EPSP) over time, action potentials were evoked at a rate of 1 Hz for 800-1000 trials. In three out of seven synapses the chemical component remained at a similar amplitude, while in four cases a progressive decrease (up to 35%) occurred. The electrotonic component remained at a similar amplitude in all cases. 3. During paired pulse stimulation of the reticulospinal cell body (pulse interval 65 ms) the chemical EPSP component showed a net facilitation in all cases tested [from 0.64 +/- 0.35 to 0.89 +/- 0.48 (SD) mV, n = 13], while the peak amplitude of the electrotonic component was unchanged (1.37 +/- 0.68 and 1.36 +/- 0.66 mV, respectively). Recording of the axonal action potential during paired pulse stimulation showed that the width of the first and second action potential did not differ [1/2 width (2.48 +/- 0.39 ms and 2.48 +/- 0.42 ms, respectively; n = 8)]. 4. The degree of facilitation varied markedly between different synapses, ranging from an increase of a few percent to a two-fold increase (24 +/- 16% mean change of total EPSP amplitude, corresponding to 44 +/- 26% mean change of chemical EPSP amplitude). This type of variability was also observed in synapses made from the same unbranched reticulospinal axon onto different postsynaptic cells. 5. When paired pulse stimulation was applied to the reticulospinal axon in the very vicinity of the synaptic area (0.1-1 mm) a net depression of the chemical component occurred in 11 out of 19 cases, and in the remaining cases the level of net facilitation was lower as compared with cell body stimulation (range between +17 and -23% change of total EPSP amplitude; mean -5%; n = 19). 6. To test if the change of the EPSP plasticity during local stimulation correlated with an increased transmitter release, two microelectrodes were placed in the same reticulospinal axon at different distances from the synaptic area.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 7983522 TI - Effects of vestibular stimulation on acetylcholine release from rat hippocampus: an in vivo microdialysis study. AB - 1. The effects of electrical stimulation to the round window of the inner ear and caloric vestibular stimulation on the in vivo release of acetylcholine (ACh) from rat hippocampus were investigated, using brain microdialysis coupled with high performance liquid chromatography-electrochemical detection. 2. Hippocampal ACh release was increased to 152% of the basal release by 1-Hz, 200-ms, and 500 microA electrical stimulation to the round window. This effect was dependent on current intensity. 3. Microinjection of 6,7-dinitroquinoxaline-2,3-dione (DNQX) (10 nmol/0.2 microliter), an antagonist of the non-N-methyl-D-aspartate (non NMDA) type of glutamate receptor, into the medial vestibular nucleus blocked the increase of hippocampal ACh release by electrical stimulation to the round window. In contrast, microinjection of DNQX (10 nmol/0.2 microliter) into the ventral cochlear nucleus did not inhibit the increase of hippocampal ACh release by electrical stimulation to the round window. 4. Electrical stimulation of the round window increased histamine release from the medial septum, which is the origin of the hippocampal cholinergic terminals. However, the depletion of neuronal histamine by alpha-fluoromethylhistidine (100 mg/kg ip) did not suppress the vestibular-evoked release of hippocampal ACh. 5. Although caloric stimulation with water at 37 degrees C did not affect the hippocampal ACh release, the release was increased to 131% of the basal release by caloric stimulation with hot water at 45 degrees C and was also increased to 160% of the basal release by caloric stimulation with ice water, suggesting that the changes in activities of vestibular afferents increased the hippocampal ACh release.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 7983523 TI - Synaptic mediation from cutaneous mechanical nociceptors. AB - 1. Responses of dorsal horn neurons to cutaneous mechanical stimulation were studied in an in vitro preparation of hamster spinal cord with partially intact innervation from an isolated patch of hairy skin. Stable extracellular and intracellular recordings were obtained from cells with different mechanoreceptive properties similar to those reported for other species in vivo. Analyses were made of the intracellular responses of 25 dorsal horn neurons activated selectively by mechanical stimulation to the skin patch. 2. Bath application of the broad spectrum, excitatory amino acid (EAA) receptor antagonist, kynurenic acid (1 mM) blocked excitation of 7 of 8 high-threshold mechanoreceptive units by either cutaneous nerve volleys or mechanical stimulation of the skin. This concentration of kynurenic acid suppressed peripherally evoked responses in 8 of 14 neurons responsive to innocuous mechanical stimuli. 3. High-threshold mechanoreceptive neurons of the superficial dorsal horn exhibited one of three distinctive patterns of postsynaptic potentials in response to electrical stimulation of cutaneous afferent fibers: 1) a simple fast excitatory postsynaptic potential (EPSP), 2) a fast EPSP with a prolonged decay phase lasting between 100 and 1,000 ms, and 3) a multiphasic response dissociable on the basis of stimulus strength consisting of a fast EPSP followed by a hyperpolarizing inhibitory postsynaptic potential (IPSP) (duration 80-100 ms). Gentle mechanical stimuli initiated inhibition from areas adjacent to the high threshold mechanically excitatory field; this suggests that membrane hyperpolarization in these neurons was evoked by input from low-threshold mechanoreceptors. 4. Bath application of 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX, 10 microM), a competitive EAA antagonist selective for non-N-methyl-D aspartate (non-NMDA) receptor subtypes, substantially or completely (56-100%) suppressed EPSPs evoked from cutaneous afferent fibers in high-threshold mechanoreceptive neurons. CNQX also decreased the membrane depolarization, the frequency of EPSPs, and the frequency of action potentials evoked by mechanical stimulation of the receptive field. 5. CNQX (10 microM) or kynurenic acid (1 mM) had considerably weaker effects on IPSPs than on EPSPs evoked from the periphery in superficial dorsal horn neurons. IPSP amplitudes were unchanged by these agents in some neurons and decreased by only 20-25% in others. 6. We conclude that L-glutamate acting on non-NMDA receptors mediates fast synaptic excitation of superficial dorsal horn neurons from peripheral mechanical nociceptors with myelinated fibers. Furthermore, the observations imply either an agent other than L-glutamate or one acting at different membrane receptors is a synaptic mediator for other peripheral afferent units including some activated by innocuous mechanical stimuli. PMID- 7983524 TI - Action potential propagation through embryonic dorsal root ganglion cells in culture. I. Influence of the cell morphology on propagation properties. AB - 1. In this and the companion paper the reliability of action potential (AP) propagation through dorsal root ganglion (DRG) cells was investigated. Experimental data were collected from DRG cells of embryonic rat slice cultures of the spinal cord. A field stimulation electrode was used to elicit an AP in the axon. The propagated AP or, in case of conduction block, its electronic residue (ER), was measured intracellularly in the soma of the DRG cell. 2. The morphological and electrophysiological data combined with published data from voltage-clamp studies were taken to implement a compartmental computer model, which allows a precise description of the propagating AP and the channel kinetics at any point along the axon. 3. The safety factor for conduction was found to be low. Thus failures of AP invasion of the DRG cell soma could occur at sites of impedance mismatch when a hyperpolarizing current was applied, a second stimulus felt into the relative refractory period of the first, or when the axon was repetitively stimulated. 4. The ERs of the failed APs had discrete amplitude levels, suggesting that the failures were always caused at the same site along the axon. These sites of low safety factor were found to be the branch point in the unipolar DRG cell and the entrance of the stem piece into the soma in both cell types, the bipolar as well as the unipolar. 5. A systematic comparison of bipolar and unipolar DRG cells showed that the AP conduction through the latter is more reliable. For large cell bodies, the unipolar configuration is needed for save conduction. 6. Conduction through unipolar DRG cells is faster than through bipolar cells because the electrical load of the soma is masked by the high resistive stem piece. The length of this stem piece is correlated inversely to the delay caused at the branch point, as the electrical load of the soma is more efficiently masked by a long stem piece. PMID- 7983525 TI - Action potential propagation through embryonic dorsal root ganglion cells in culture. II. Decrease of conduction reliability during repetitive stimulation. AB - 1. The reliability of the propagation of action potentials (AP) through dorsal root ganglion (DRG) cells in embryonic slice cultures was investigated during repetitive stimulation at 1-20 Hz. Membrane potentials of DRG cells were recorded intracellularly while the axons were stimulated by an extracellular electrode. 2. In analogy to the double-pulse experiments reported previously, either one or two types of propagation failures were recorded during repetitive stimulation, depending on the cell morphology. In contrast to the double-pulse experiments, the failures appeared at longer interpulse intervals and usually only after several tens of stimuli with reliable propagation. 3. In the period with reliable propagation before the failures, a decrease in the conduction velocity and in the amplitude of the afterhyperpolarization (AHP), an increase in the total membrane conductance, and the disappearance of the action potential "shoulder" were observed. 4. The reliability of conduction during repetitive stimulation was improved by lowering the extracellular calcium concentration or by replacing the extracellular calcium by strontium. The reliability of conduction decreased by the application of cadmium, a calcium channel blocker, 4-amino pyridine, a fast potassium channel blocker, or apamin or muscarine, the blockers of calcium dependent potassium channels. The reliability of conduction was not effected by blocking the sodium potassium pump with ouabain or by replacing extracellular sodium with lithium. 5. In the period with reliable propagation cadmium, apamin, and muscarine reduced the amplitude of the AHP. The shoulder of the action potential was more pronounced and not sensitive to repetitive stimulation when extracellular calcium was replaced by strontium. It disappeared when cadmium was applied. 6. In DRG somata changes of the intracellular Ca2+ concentration were monitored by measuring the fluorescence of the Ca2+ indicator Fluo-3 with a laser scanning confocal microscope. During repetitive stimulation, an accumulation of intracellular calcium occurred that recovered very slowly (tens of seconds) after the AP trains. 7. Computer model simulations performed in analogy to the experimental protocols produced conduction failures during repetitive stimulation only when the calcium currents during the APs were reduced. 8. From these findings it is concluded that conduction failures during repetitive stimulation are dependent on an accumulation of intracellular calcium leading to an inactivation of calcium currents, combined with small contributions of an accumulation of extracellular potassium and a summation of slow potassium conductances. PMID- 7983526 TI - Modulation of the input/output function of rat piriform cortex pyramidal cells. AB - 1. In transverse brain slice preparations of rat piriform cortex, we characterized the repetitive firing properties of layer II pyramidal cells in control conditions (n = 78) and during perfusion of the cholinergic agonist carbachol (n = 26), with the ultimate goal of developing realistic computational simulations of the cholinergic modulation of the input/output function of these neurons. The response of neurons to prolonged (1 s) intracellular current injections was examined at a full range of current injection amplitudes, providing three-dimensional plots of firing frequency versus current amplitude versus time. 2. All neurons showed adaptation in response to intracellular current injection, with repetitive generation of action potentials at frequencies that were highest at the onset of the pulse and that decreased considerably thereafter. Substantial differences were observed between cells with regard to their rates of adaptation and the maximal number of action potentials they could generate during the current pulse. 3. The adaptation characteristics of each neuron were quantified by plotting the number of action potentials generated in 1 s as a function of the normalized current injection amplitude and measuring the area beneath this plot of the number of spikes versus current injection amplitude (S-I plot). This value was termed S-I value and allowed neurons to be plotted on a continuum including neurons showing strong adaptation (S-I value < 8.0) and neurons showing weak adaptation (S-I value > 8.0). The group showing weak adaptation contained 36% of the cells in control solution and 93.8% of the cells in 20 microM carbachol. 4. Neurons showing strong adaptation did not differ significantly from neurons showing weak adaptation in control conditions in measurements of resting potential, input resistance, threshold, and spike amplitude. Only a small difference was found in frequencies of firing measured soon after pulse onset (after 100 ms). This implies that differences in S-I values are primarily due to different rates of adaptation in later parts of the response. 5. Perfusion with solution containing the cholinergic agonist carbachol (2-100 microM) or 0 Ca2+ and 200 microM cadmium resulted in a substantial increase in the S-I values of neurons showing strong adaptation but had only a small effect on their initial firing rates. The effect on weakly adapting cells was smaller. In the presence of 20 microM carbachol, neurons showed a distribution shifted predominantly toward weak adaptation (n = 26).(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 7983527 TI - Effects of insulin and hypoglycemia on the auditory brain stem response in humans. AB - 1. This study aimed to differentiate effects of insulin and hypoglycemia on sensory brain stem functions in humans. Auditory brain stem responses (ABR) were examined in 30 healthy men during euglycemia and after 20 and 50 min of steady state hypoglycemia of 2.6 mM induced with human insulin (HI) in one session and porcine insulin (PI) in another session. 2. Levels of blood glucose and serum insulin were identical in both sessions during HI and PI infusion. 3. Hypoglycemia increased interpeak latencies III-V (+71 microseconds; P < 0.001) and I-V (+123 microseconds; P < 0.001), whereas changes in the latency of wave I were not significant. 4. After 20 min of constant hypoglycemia, increases in the interpeak latencies I-V and III-V were significantly more pronounced during infusion of PI than HI. These differences disappeared with time spent in hypoglycemia, i.e., after 50 min of hypoglycemia. 5. Apart from the delaying effect of hypoglycemia on neuronal transmission within the sensory brain stem, the results provide evidence for a separate influence of insulin on these functions. PMID- 7983528 TI - Protein kinase C inhibitors decrease hyperalgesia and C-fiber hyperexcitability in the streptozotocin-diabetic rat. AB - 1. We have previously demonstrated that although rats with streptozotocin-induced diabetes (STZ-D) have decreased behavioral mechanical nociceptive thresholds (hyperalgesia), their C-fiber primary afferent mechanical (von Frey hair) thresholds are not altered. Instead, when stimulated with a standardized sustained suprathreshold mechanical stimulus, C-fibers from STZ-D rats were found to have an increased number of spikes (hyperexcitability). We suggested that this C-fiber hyperexcitability contributes to the behavioral hyperalgesia and that agents that reverse the hyperalgesia may act by decreasing this hyperexcitability. Because protein kinase C activity contributes to C-fiber afferent excitability, we examined the effect of agents that inhibit protein kinases on behavioral mechanical nociceptive thresholds and on the response of C fiber afferents to sustained mechanical stimulation. 2. The effects of intradermal injection of two protein kinase inhibitors, staurosporine and protein kinase C pseudosubstrate inhibitor peptide [PKC(19-36)], on behavioral mechanical nociceptive thresholds were determined using the Randall-Selitto paw-withdrawal device. These agents increased the mechanical nociceptive threshold of STZ-D rats in a dose-dependent manner but did not alter nociceptive threshold in control rats. 3. The same agents were tested for their effects on single C-fiber mechanical thresholds and excitability in response to suprathreshold (445 g) mechanical stimulation. Intradermal injection of staurosporine or PKC(19-36) significantly reduced the response of C-fibers from STZ-D rats to sustained suprathreshold mechanical stimulation but did not alter the response of C-fibers from control rats to the same stimulation. Neither agent altered mechanical threshold in C-fibers from either STZ-D or control rats. 4. In this study we found that both the mechanical behavioral hyperalgesia and the C-fiber hyperexcitability to mechanical stimuli seen in STZ-D rats are reduced by agents that inhibit protein kinase C. This evidence supports our hypothesis that C-fiber hyperexcitability, in part mediated by PKC activity, contributes to hyperalgesia in this model of diabetic neuropathy. PMID- 7983529 TI - A characterization of excitatory postsynaptic potentials in the avian nucleus magnocellularis. AB - 1. The activation of current-clamped neurons in the chick nucleus magnocellularis (nMAG) by eighth nerve stimulation has been studied in a brain slice preparation using patch electrodes. Single presynaptic stimuli produced rapidly rising, suprathreshold, excitatory postsynaptic potentials (EPSPs) with a synaptic delay of approximately 0.4 ms. Spontaneous, miniature EPSPs (mEPSPs) were evident in control extracellular solution and in the presence of tetrodotoxin (TTX). 2. The EPSP was composed of a large, brief component that was sensitive to antagonists of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors, and a smaller, slowly decaying component that was sensitive to both N-methyl-D aspartate (NMDA) and AMPA receptor antagonists. 3. Injection of depolarizing current steps revealed a strong outward rectification of the membrane conductance at potentials close to the resting potential. Consequently, neurons could fire only a single, TTX-sensitive action potential during a current step. The conductance responsible for this rectification was sensitive to 1 mM 4 aminopyridine but not to 1 mM tetraethylammonium. 4. Following the termination of depolarizing current pulses, membrane potential decayed with a half-time (t1/2) that decreased as the depolarizing current increased, reaching approximately 0.25 ms for a depolarization from rest of 20 mV. The t1/2 for the decay of EPSPs matched the membrane t1/2, indicating that the underlying synaptic conductance decays more quickly than the membrane t1/2. 5. The slow phase of the EPSP was always longer than the membrane t1/2 and increased in size with hyperpolarization. This result is consistent with the contribution of AMPA receptors to the slow, as well as fast, EPSP. 6. The safety factor for transmission with low-frequency stimuli was large, as indicated by the rise time of the EPSP, the extent to which the EPSP shunted the action potential, and the size of EPSPs after prolongation of the synaptic conductance by cyclothiazide. 7. During repetitive synaptic stimulation, the slow EPSPs summated to produce a plateau depolarization of 10-20 mV. The plateau potential was only partially blocked by NMDA receptor antagonists. 8. During trains of stimuli, the faster EPSPs rode atop the plateau potential and could drive action potentials at rates up to 500 Hz for short periods. Synaptic depression was evident during trains, such that EPSPs often fell below threshold after 5-10 stimuli at rates above 200 Hz. EPSPs could remain suprathreshold for several seconds at 50 Hz.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 7983530 TI - Multiple components of voltage-dependent potassium current in normal rat anterior pituitary cells. AB - 1. Voltage-dependent K+ currents were studied in normal rat anterior pituitary cells using the patch-clamp technique. To obtain cultures enriched for lactotrophs, density gradient centrifugation was performed on pituitary cells isolated from lactating rats. 2. Depolarizations to about -30 mV from a holding potential of -80 mV activate a rapidly inactivating [time constant (tau) approximately 15-20 ms at -20 mV]K+ current. This transient current activated at low voltages (termed IA) is abolished by 5 mM external 4-aminopyridine (4-AP) but is largely resistant to external tetraethylammonium (TEA) (< or = 30 mM). 3. Recovery from inactivation of IA is fast, with a tau of 100-200 ms at -80 mV. Deactivation is also fast (tau approximately 2.2 ms at -50 mV). The voltage of half-activation of IA is approximately -20 mV. The current is completely inactivated at a holding potential of -40 mV. 4. Voltage-dependent K+ current activated by depolarizations from a holding potential of -40 mV was first detectable at about -20 mV (high voltage-activated) and had a time course that varied among cells. 5. Deactivation of high voltage-activated K+ current was best described by the sum of two exponentials, with tau of about 3.7 and 30 ms at -50 mV. Both components reversed close to the equilibrium potential for K+. 6. The amplitudes of the two tail currents were independent of each other when variable duration commands were used to activate current. The amplitude of the fast component was largest with 10- to 20-ms commands to +40 mV and was reduced (< or = 50%) with 136-ms commands. The slow component amplitude reached a peak by 40 ms and remained constant for commands < or = 136 ms at +40 mV. 7. The contribution of each component to the total high voltage-activated tail current was variable among cells, with the amount of fast component correlating with the amount of inactivation produced by commands to +40 mV. 8. The two components of tail current activated by depolarizations from the -40 mV holding potential were abolished by external TEA (10 mM). 4-AP (5 mM externally) selectively abolished the fast component of high voltage-activated tail current while only partially reducing the slow component. 9. These results suggest that normal rat anterior pituitary cells possess at least three distinct types of voltage-dependent K+ current: a low voltage-activated, transient current (IA) and two high voltage activated currents.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 7983531 TI - The retinal dopamine network alters the adaptational properties of retinal ganglion cells in the cat. AB - 1. Single-unit extracellular recordings of optic tract fibers were used to study ganglion cell (GC) response properties of the intact cat eye before and after the intravitreal injection of haloperidol or SCH23390, dopamine-specific antagonists. Nearly all of the dopaminergic cells in the cat retina are amacrine cells (ACs); thus the dopamine antagonists are thought to primarily block the postsynaptic effects of these dopaminergic amacrine cells. All GCs encountered were subjected to a battery of receptive-field (RF) tests, including classification as X or Y, and as ON or OFF. 2. The effects of haloperidol were greatest in the light adapted OFF-center pathways and especially in the OFF-center Y-cell. Within 30 min of haloperidol injection, both the spontaneous and light-evoked activity of the OFF-center Y-cell fell to zero, but when the same cell was exposed to lower levels of steady-state background illumination (scotopic levels), the response of the cell once again became robust. 3. OFF-Center Y-cells that had partially recovered from the drug effects and OFF-center X-cells recorded when the drug effect was maximal both possessed intensity-response curves that were shifted to the right of normal. 4. Recovery from the drug effects reflect supranormal responses after the initial response reductions and may be due to haloperidol's action on the dopamine autoreceptor. 5. Of the ON-center cells, only the Y-cells showed response alterations; possessing higher spontaneous activities and slightly reduced amplitudes to RF center (RFC) illumination. 6. The effects of SCH23390 paralleled those of haloperidol except that the onset was faster and the duration of the action of SCH23390 was much shorter, and no supranormal responses followed the initial effects. 7. Dark-adaptation functions of OFF-center GCs revealed a normal rod-cone shift; however, SCH23390 eliminated the rod-cone break, and threshold quickly fell to that of the rod mechanism. 8. The dopaminergic neurons of the cat retina appear to play an important role in regulating the activity of retinal OFF-center pathways in the photopically adapted eye, and one of its functions may be to control the relative contributions of the rod and cone systems to the response properties of light adapted OFF-center GCs. 9. It is argued that dopamine is released in the light and enhances cone pathway activity, perhaps in the outer retina at bipolar and horizontal cells, and suppresses rod pathway activity, perhaps in the inner retina at amacrine cells. PMID- 7983532 TI - Origin of the apparent tissue conductivity in the molecular and granular layers of the in vitro turtle cerebellum and the interpretation of current source density analysis. AB - 1. We determined the origin of the apparent tissue conductivity (sigma 2) of the turtle cerebellum in vitro. 2. Application of a current with a known current density (J) along the longitudinal axis of a conductivity cell produced an electric field in the cerebellum suspended in the cell. The measured electric field (E) perpendicular to the cerebellar surface indicated a significant inhomogeneity in sigma a (= J/E) with a major discontinuity between the molecular layer (0.25 +/- 0.05 S/m, mean +/- SD) and granular layers (0.15 +/- 0.03 S/m) (n = 39). 3. This inhomogeneity was more pronounced after anoxic depolarization. The value of sigma a decreased to 0.11 +/- 0.03 and 0.040 +/- 0.008 S/m in the molecular and granular layers, respectively. The ratio of sigma a S in the two layers increased from 1.67 in the normoxic condition to 2.75 after anoxic depolarization. 4. This difference in sigma a across the two layers was present within the range of frequencies (DC to 10 kHz) studied where the phase of sigma a was small (less than +/- 2 degrees) and therefore sigma a was ohmic. 5. The inhomogeneity in sigma a was in part due to an inhomogeneity in the extracellular conductivity (sigma e) as determined from the extracellular diffusion of ionophoresed tetramethylammonium. Like sigma a, the value of sigma e was also higher in the molecular layer (0.165 S/m) than in the granular layer (0.097 S/m). The inhomogeneity in sigma e was due to a smaller tortuosity and a larger extracellular volume fraction in the molecular layer compared with the granular layer. 6. sigma a was, however, consistently higher, by approximately 50%, than sigma e. A core conductor model of the cerebellum indicated that these discrepancies between sigma a and sigma e were attributable to additional conductivity produced by a passage of the longitudinal applied current through the intracellular space of Purkinje cells and ependymal glial cells, with the glial compartment playing the dominant role. Cells with a long process and a short space constant such as the ependymal glia evidently enhance the effective "extracellular" conductivity by serving as intracellular conduits for the applied current. The result implies that the effective sigma e may be larger than sigma e for neuronally generated currents in the turtle cerebellum because the space constant for Purkinje cells is several times greater than that for the ependymal glia and consequently Purkinje cell-generated currents travel over a long distance relative to the space constant of glial cells.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 7983533 TI - Regulation of glycine-insensitive desensitization of the NMDA receptor in outside out patches. AB - 1. Regulation of desensitization of N-methyl-D-aspartate (NMDA) receptors was studied in outside-out patches from cultured rat hippocampal neurons. The progressive increase in a glycine-insensitive form of desensitization after patch excision did not require extracellular Ca2+ concentration nor was it use dependent, but the initial extent of desensitization after patch formation was reduced by intracellular bis-(o-aminophenoxy)-N,N,N',N'-tetraacetic acid (BAPTA). 2. Preincubation of neurons with 30 microM dantrolene, which can decrease Ca2+ release from intracellular stores, also reduced the degree of NMDA receptor desensitization just after patch excision. Thus the development of this form of desensitization appears to be triggered by a transient increase of intracellular calcium. 3. The extent of glycine-insensitive desensitization was also reduced by intracellular ATP-gamma S, high concentrations of the phosphatase inhibitor, microcystin, or intracellular application of a peptide inhibitor of calcineurin. These data support the hypothesis that glycine-insensitive desensitization of the NMDA receptor in outside-out patches is regulated in part by the phosphorylation state of the receptor or an associated protein. 4. Because the NMDA channel is very permeable to Ca2+, the extent of phosphorylation and thus desensitization of the receptors may be sensitive to synaptic activation and could serve as a feedback mechanism to decrease the intensity of excitation and plasticity. PMID- 7983534 TI - Multiple components of calcium current in acutely dissociated dentate gyrus granule neurons. AB - 1. Specific Ca2+ channel blocker were used to isolate and characterize different components of whole cell Ba2+ current in granule neurons acutely dissociated from guinea pig hippocampal slices. 2. Granule cell Ba2+ current peaked around +5 mV, whether elicited by step or ramp commands, and was completely blocked by 100 microM Cd2+. 3. Saturating doses (> or = 5 microM) of the dihydropyridine antagonist, nimodipine, blocked 39% of the total current, and the inhibition was partially reversible. Nimodipine had a greater effect on current at the end of a depolarizing step, suggesting some voltage dependence of its action. 4. Saturating doses (> or = 3 microM) of omega-conotoxin-GVIA irreversibly blocked 21% of the total current and did not occlude subsequent nimodipine inhibition. 5. High concentrations (> or = 100 nM) of omega-agatoxin-IVA irreversibly blocked another 20% of the total current. The effect of omega-Aga-IVA was quite slow, but saturated after several minutes at 200 nM concentration. A high dose (1 microM) produced rapid effects that were used to quantify the magnitude of block. 6. When applied together, all three blockers inhibited nearly the same amount of total current (77%) as would be expected from the sum of each blocker applied individually (80%), suggesting that the three antagonists blocked different channel types. 7. Quantitatively similar results were obtained for the effect of each blocker alone and in combination on currents elicited by depolarizing ramp commands. Ramp currents blocked by each antagonist (difference ramps) all peaked near the same potential as the initial control ramp, indicating very similar activation properties for the three current components. Difference currents elicited by step commands similarly showed little difference among the three components in their kinetics of inactivation during relatively brief (30 ms) depolarizations. With longer steps, however, the omega-CgTX-GVIA-sensitive component showed some inactivation, whereas the omega-Aga-IVA-sensitive current did not inactivate. 8. The component of current resistant to all three blockers (approximately 23% of total current) was not inhibited by omega-conotoxin-MVIIC, but was half blocked by 50 microM Ni2+. This Ni(2+)-sensitive component showed relatively rapid inactivation and peaked at a somewhat lower potential (-10 mV) than the control current. The resistant current was also inactivated by approximately 50% by holding at -60 compared with -80 mV.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 7983535 TI - Neural analogue of long-term sensitization training produces long-term (24 and 48 h) facilitation of the sensory-to-motor neuron connection in Aplysia. AB - 1. An in vitro analogue of long-term sensitization training was used to gain insights into the mechanisms and time course of the memory for long-term sensitization in Aplysia. The analogue, consisting of four blocks of shocks, was delivered to peripheral nerves of the isolated pleural-pedal ganglia, which contain the sensory neurons and motor neurons that mediate the tail withdrawal reflex. 2. Long-term facilitation of the connections between the sensory neurons and motor neurons was produced by the conjoint stimulation of two peripheral nerves, P8 and P9. Long-term facilitation, however, was not observed after conjoint stimulation of three nerves, P7, P8, and P9. 3. The preparation was viable and stable (no changes in the amplitudes of excitatory postsynaptic potentials (EPSPs) and membrane properties in controls) for at least 48 h. Moreover, the long-term facilitation persisted for at least 48 h. 4. We observed no significant long-term changes in the resting membrane potentials of the sensory and motor neurons or in the input resistance of the motor neurons 24 and 48 h after the conjoint stimulation of nerves P8 and P9. Thus changes in these biophysical properties do not appear to contribute to the expression of long-term facilitation. 5. The finding that conjoint stimulation of three nerves, P7, P8, and P9, produced no long-term facilitation raised the possibility that stimulation of nerve P7 alone might produce long-term inhibition that opposes the facilitatory effects induced by conjoint stimulation of nerves P8 and P9. Stimulation of nerve P7 alone, however, had no long-term inhibitory effect on the EPSPs.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7983536 TI - Effect of muscimol microinjections into the prepositus hypoglossi and the medial vestibular nuclei on cat eye movements. AB - 1. For horizontal eye movements, previous observations led to the hypothesis that the legendary neural integrator necessary for correct gaze holding, adequate vestibuloocular reflex (VOR), and optokinetic nystagmus, was located in the region of the complex formed by the nucleus prepositus hypoglossi (NPH) and the medial vestibular nucleus (MVN). 2. The aim of the present study was to test the respective contributions of the NPH, of the rostral part of the MVN, which contains most second-order vestibular neurons, and of the central part of the MVN to the horizontal integrator. 3. An injection of muscimol was used to inactivate each of these three zones in the cat's brain. Muscimol is a gamma-aminobutyric acid (GABA) agonist. By binding to GABAA receptors, it induces a hyperpolarization of the neurons that nullifies their activity. Muscimol was injected into the brain stem of the alert cat through a micropipette by an air pressure system. 4. The search coil technique was used to record spontaneous eye movements and the VOR induced by rotating a turntable at a constant velocity. VOR was analyzed by a new method: transient analysis of vestibular nystagmus. 5. A unilateral injection of muscimol into the NPH induced a bilateral gaze-holding failure: saccades were followed by a centripetal postsaccadic drift. A vestibular imbalance was also present but it was moderate and variable. The VOR responses were distorted drastically. Through transient analysis of vestibular nystagmus, that distortion was revealed to be due more to a failure of the neural integrator than to an alteration of the vestibular input to the neural integrator. The responses to a rotation either toward the injected side or in the opposite direction were asymmetrical. The direction of that asymmetry was variable. 6. A unilateral injection of muscimol into the rostral part of the MVN caused a vestibular imbalance: in complete darkness, a nystagmus appeared, whose linear slow phases were directed toward the side of injection. 7. A unilateral injection of muscimol into the central part of the MVN induced a syndrome where a severe bilateral gaze-holding failure was combined with a vestibular imbalance. In the light, saccades were followed by a bilateral centripetal postsaccadic drift. In complete darkness, a nystagmus was observed, whose curved slow phases were directed towards the side of injection. The VOR responses were distorted drastically. Here again, that distortion was revealed by our analysis to be due more to a failure of the neural integrator than to an alteration of the vestibular input to the neural integrator.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 7983537 TI - Pre- and postsynaptic components of nicotinic long-term potentiation in the superior cervical ganglion of the cat. AB - 1. In anesthetized, atropine-treated cats we measured the acetylcholine (ACh) release into the venous effluent of the superior cervical ganglion (SCG) and the nictitating membrane (NM) contraction evoked by a 2-Hz, 20-s test train to the ipsilateral cervical sympathetic trunk (CST). We also measured NM contraction produced by injection of ACh (50 micrograms) or 1,1-dimethyl-4-phenylpiperazinium (DMPP, 5 micrograms) into the arterial supply of the ipsilateral SCG. 2. After a 10- to 30-s, 40-Hz conditioning train to CST these responses were all potentiated. The potentiation of the NM response evoked by the test train or by the exogenous agonists was long lasting (90% decay in 64 +/- 10 min, mean +/- SE, for the train-evoked response; 42 +/- 9 min for the response to injected ACh; 61 +/- 18 min for the response to injected DMPP), whereas the potentiation of the ACh release lasted only for 9 min. 3. On the assumption that ACh and DMPP injected into the ganglionic arterial supply acted postsynaptically, these data suggest that the main mechanism of the long-term potentiation (LTP) of nicotinic transmission in SCG is an increase in postsynaptic responsiveness. Because the response to KCl (250 micrograms) injected into the ganglionic arterial supply was not potentiated after the conditioning train, a posttrain increase in excitability of the postsynaptic membrane is not likely to be the cause of the postsynaptic increased responsiveness to ACh and DMPP.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7983538 TI - Ca2+ cooperativity in neurosecretion measured using photolabile Ca2+ chelators. AB - 1. The photolabile Ca2+ chelator DM-nitrophen was injected into crayfish motor neuron terminals and photolyzed with light flashes of different intensity to determine the cooperativity of Ca2+ action in releasing neurotransmitter. 2. Each flash elicited a phasic postsynaptic response resembling an excitatory junctional potential, apparently due to a presynaptic "spike" in intracellular calcium concentration ([Ca2+]i). 3. When postsynaptic currents were measured under voltage clamp, a Ca2+ cooperativity of approximately 3-4 was inferred from a supralinear dependence of responses on changes in peak [Ca2+]i caused by flashes differing in intensity by 32-46%. 4. A similar Ca2+ cooperativity was inferred from postsynaptic potentials in response to flashes of varying intensity. 5. The time course of transmitter release indicated by flash responses had slightly slower rising and falling phases than excitatory postsynaptic potentials. There was also a slow tail of transmitter release lasting for approximately 200 ms after a flash. 6. This time course was explained quantitatively by simulations of DM-nitrophen photolysis and binding reactions and a model of Ca2+ activation of transmitter release. PMID- 7983539 TI - Morphology of primary somatosensory cortical neurons receiving input from the tooth pulp. AB - 1. To elucidate the morphological and electrophysiological characteristics of tooth pulp-driven neurons (TPNs) in the primary somatosensory cortex (SI), we injected neurobiotin into TPNs whose electrophysiological characteristics had been identified. 2. TPNs, responsive to electrical stimulation of the tooth pulp, were recorded intracellularly and injected from areas 3a and 3b of SI. A total of 58 TPNs in SI were successfully injected and reconstructed. Nineteen of these TPNs were located in area 3a and 39 in area 3b. Three area 3a TPNs were identified in lamina II, eight in lamina III, seven in lamina V, and one in lamina VI. Five 3b TPNs were identified in lamina II, 19 in lamina III, 7 in lamina IV, 7 in lamina V, and 1 in lamina VI. 3. Thalamic and tooth pulp latencies of lamina III and IV TPNs were shorter than those of lamina II and V TPNs. On the other hand, lingual and masseteric nerve latencies of TPNs were not consistent with thalamic and tooth pulp latencies. 4. Three of 19 area 3a TPNs and 7 of 39 area 3b TPNs were classified as pulp-specific TPNs, which received only tooth pulp input. Thirteen of 19 area 3a TPNs and 24 of 32 area 3b TPNs were classified as low-threshold mechanoreceptive TPNs, which responded to nonnoxious mechanical stimulation of the receptive field, and only 2 area 3b TPNs were classified as wide-dynamic range TPNs. Six of the area 3a TPNs and 14 of the area 3b TPNs responded to electrical stimulation of the lingual and/or masseteric nerves. Nociceptive-specific TPNs were not recorded in this study. 5. Lamina II TPNs in areas 3a and 3b had small somata, and those in area 3a had dendrites spreading into laminae I-II. Two TPNs in area 3a had axon collaterals extending into area 4. In contrast, area 3b TPNs in lamina II have dendrites spreading into laminae I-III. Their axons did not extend deeply into the subcortical regions, and the axon collaterals reached into area 3a. 6. Lamina III TPNs were classified according to their morphological characteristics as pyramidal or nonpyramidal stellate TPNs. Pyramidal lamina III TPNs had typical pyramidal somata, like those of lamina V pyramidal cells. Furthermore, those in areas 3a and 3b had dendrites with numerous spines spreading into laminae I-III, and some of the area 3a TPNs have axons with collaterals projecting into area 4. Lamina III area 3b TPNs had morphological properties similar to those in area 3a.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 7983540 TI - Time course of locomotor recovery and functional regeneration in spinal cord transected lamprey: in vitro preparations. AB - 1. Previous studies indicate that after transection of the rostral spinal cord, larval lamprey begin to recover locomotor behavior 2 wk posttransection and recovery is complete at approximately 8 wk. To examine the mechanisms underlying behavioral recovery after spinal cord transection, in the present study the time course and extent of recovery of locomotor function was examined in in vitro brain/spinal cord preparations. With these preparations the contributions of functional regeneration of descending brain stem projections to recovery of spinal locomotor function can be examined in the absence of mechanosensory inputs and descending propriospinal relay systems. 2. In in vitro preparations from normal lamprey, stimulation in brain stem locomotor regions resulted in direct descending activation of locomotor networks in the rostral, middle, and caudal spinal cord. 3. At 4 wk posttransection, in vitro locomotor activity was usually confined to the rostral spinal cord a few millimeters below the transection site. At 8 wk posttransection locomotor activity was present in both the rostral and middle spinal cord, and spinal locomotor networks at these levels could be directly activated by restored descending projections from the brain stem. 4. At 16-32 wk posttransection locomotor activity similar to that seen in normal animals was present along the spinal cord. Additional manipulations suggest that at 32 wk posttransection descending axons from brain stem command/initiation neurons had grown for relatively long distances and could directly activate the locomotor networks in the caudal spinal cord. At each recovery time examined the ranges of locomotor parameters (cycle time, burst proportion, and intersegmental phase lag) overlapped with those in normal animals. 5. In vitro locomotor activity in spinal cord-transected animals could be recorded at progressively more caudal levels below the transection site during the course of recovery. However, locomotor activity in in vitro preparations occurred for shorter distances below the lesion than in whole animals at comparable recovery times. 6. Our recent double-labeling experiments suggest that behavioral recovery in spinal cord-transected lamprey is largely due to true regeneration of preexisting descending axons rather than development of new descending projections. Thus, these results in conjunction with our behavioral, in vitro, and anatomic data suggest that functional regeneration of descending axons from the brain, as well as other mechanisms such as descending propriospinal relay systems and mechanosensory inputs, account for the gradual restoration of locomotor function in spinal cord-transected lamprey. PMID- 7983541 TI - Electronic structure of motoneurons in spinal cord slice cultures: a comparison of compartmental and equivalent cylinder models. AB - 1. Voltage-clamp, current-clamp, and morphological data were obtained from visually identified motoneurons in organotypic cocultures of rat embryonic spinal cord, dorsal root ganglia, and skeletal muscle. The cells were injected with Biocytin during whole-cell patch-clamp recordings and stained with horseradish peroxidase. 2. The somata and dendritic trees of the cells were reconstructed with a semiautomatic reconstruction system. The motoneurons had a common multipolar shape. An elliptic soma gave rise to 3-9 stem dendrites with a mean diameter of 2.5 +/- 0.9 (SD) micron terminating in 24 +/- 7 dendritic endings. The mean total dendritic path length was 3,306 +/- 1,075 microns. The mean total membrane surface area was 15,594 +/- 10,404 microns 2 with a dendritic to somatic membrane surface area ratio of 3.4 +/- 1.4 (n = 7 cells). 3. The ratio between the sum of the diameters of the two daughter branches and the diameter of the parental branch each raised to the 3/2 power at all branch points was 1.3 +/- 0.28 (n = 8 cells). The dendritic trees of the cells tapered continuously from the soma to the distal ends. The mean normalized dendritic trunk parameter of all cells was 0.62 +/- 0.22. 4. The motoneurons had a mean input resistance RN of 498 +/- 374 M delta, a mean membrane time constant (tau m) of 22 +/- 4.6 ms, and a mean dendritic dominance (rho) of 2.7 +/- 0.86 (n = 5 cells). The mean electronic length (L) calculated from tau m and the slowest voltage-clamp time constant (tau VC1) was 0.7 +/- 0.04 (n = 7 cells). 5. The specific membrane capacitance (Cm) estimated from the charge of the capacitive current during a voltage step and the total membrane surface area was 1.08 +/- 0.3 microF/cm2 (n = 6 cells). 6. Compartmental computer models were constructed of individual cells. Experimental and simulated voltage transients were matched with Cm = 1 microF/cm2, a uniform membrane resistivity (Rm) = tau m/Cm and a cytosolic resistivity (Ri) of 308 +/- 39 omega.cm (n = 3 cells). 7. The mean electrotonic length of the dendritic paths was 0.83 +/- 0.2 (n = 5 cells). The mean input resistance at the dendritic terminals (RT) was 1,413 +/- 260 M omega. Synaptic conductances were applied at all distal dendritic compartments of the model cells. The resulting synaptic currents were calculated at the input site and at the soma. The mean transient current attenuation ratio was 4.7 +/- 1.7 under idealized voltage-clamp conditions.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 7983542 TI - Multiple modes of activity in a model neuron suggest a novel mechanism for the effects of neuromodulators. AB - 1. Previous examination of the phase space of a mathematical model of a bursting molluscan neuron has demonstrated the existence of multiple stable oscillatory modes. The present study examined the extent to which multistability could be regulated by known modulatory agents, the consequences of that regulation on the response of the neuron to synaptic inputs, the effects of noise, and the potential of multistability to enrich the repertoire of neuromodulatory effects. 2. Coexisting stable attractors may appear when a change is made in a voltage dependent conductance in a manner that simulates the application of a neuromodulator. A small transient perturbation can shift the model neuron between stable modes, greatly amplifying the original perturbation. Thus the model becomes more sensitive to conventional synaptic inputs. These mode shifts are robust in the presence of low-amplitude synaptic noise. 3. In response to random high-amplitude synaptic noise, a model neuron rendered multistable by a simulated application of a neuromodulator produces apparently random activity, whereas in response to the same synaptic noise, a monostable model neuron produces barely perturbed regular activity. Thus an increase in the number of attractors enhances sensitivity to both conventional synaptic inputs and noise. Conversely, a decrease is associated with a reduction in sensitivity. 4. The response of a neuron to a subsequent transient perturbation in the level of neuromodulator depends on the steady-state level of the neuromodulator. For example, if the steady-state level is associated with a multistable neuron, a mode shift produced by such a transient change in the level of neuromodulator (manifested in our model as a conductance change) can persist after the conductance is returned gradually to its original value. Thus multistable dynamic activity permits the effects of a neuromodulator to persist when the neuromodulator is no longer present. 5. The mechanism of mode shifting between coexisting stable oscillatory modes introduces a number of novel possibilities with potentially profound implications for information processing and storage in a single neuron. PMID- 7983543 TI - Identification of muscle afferents subserving sensation of deep pain in humans. AB - 1. Intraneural microstimulation (INMS) and microneurography were used in combination to stimulate and record from muscle nociceptor primary afferent fibers of the common peroneal nerve of healthy volunteers. When pain evoked by INMS was projected to muscle, afferent activity could be evoked by innocuous and noxious pressure applied within the projected painful area. Conduction velocity of single fibers was determined by stimulating the receptive fields (RFs) electrically via needle electrodes inserted into the RF and measuring conduction latency and distance between the RF and recording electrode. 2. Pain projected to muscle during INMS trains 5-10 s in duration at threshold intensity for pain sensation was typically described as cramping and was well localized. Subjects mapped the area of the painful projected field (PF) over the skin using a pointer. 3. Fourteen slowly adaping mechanoreceptors with RF in muscle and with moderate to high receptor threshold were identified within or near the painful PF. Conduction velocities were in the range of Group III (n = 8) and Group IV (n = 6) fibers. Mean RF areas of Group III and Group IV afferents, determined by applying pressure percutaneously, were 2.71 +/- 1.14 (SE) cm2 and 3.40 +/- 1.08 (SE) cm2, respectively. Only one Group III afferent unit exhibited spontaneous activity (< 1 Hz). 4. One additional high-threshold mechanoreceptor was identified, with its RF located in the extensor tendon at the base of the big toe. This fiber had a conduction velocity of 32 m/s. During INMS, a well localized sharp pain was projected to the tendon.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7983544 TI - The onset of response habituation during the growth of the lateral giant neuron of crayfish. AB - 1. The postembryonic development of the crayfish LG tailflip command neuron's response to mechanosensory input was studied with standard electrophysiological techniques in animals between 1 and 12 cm long. 2. LG neurons are present in each abdominal hemisegment where they receive direct and indirect excitatory input from mechanosensory afferents. In both small and large crayfish, electrical stimulation of an abdominal ganglionic nerve containing those afferents evoked a compound excitatory postsynaptic potential (EPSP) with an early, reliable alpha component and a later, depression-prone beta wave. It is known that the alpha and beta components are produced by inputs from primary mechanosensory afferents and interneurons, respectively. 3. In crayfish < 2 cm long, LG was excited by the alpha component. When superthreshold, the alpha component triggered a single spike; additional excitation provided by the later beta wave presumably was preempted by refractoriness following the alpha spike and by recurrent inhibition of LG excited by the spike. LG was excited reliably by the alpha component in response to repeated superthreshold stimulation. 4. In crayfish between 2 and 3 cm, LG was excited more readily by the beta wave than by the alpha component. LG's beta spike response habituated to repeated stimulation at 1 Hz, and the beta EPSP depressed whereas the alpha component was largely unchanged. The appearance of the cellular substrates of habituation correlates with the reported onset of behavioral habituation of the tailflip response. Higher stimulus levels brought the alpha EPSP to threshold. Repetitive stimulation at these levels reliably evoked LG spikes from the alpha EPSP.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7983545 TI - Changes in synaptic integration during the growth of the lateral giant neuron of crayfish. AB - 1. The effect of growth on the electrotonic structure and synaptic integrative properties of the lateral giant (LG) interneuron was assessed from anatomic and electrophysiological measurements of LGs in small (1-2.4 cm) and large (9-11.2 cm) crayfish and from calculated responses of mathematical models of these neurons. Postsynaptic responses of small and large LGs were compared with model responses to determine whether the differences in the neurons' responses result from growth-related changes in their physical characteristics. 2. LG neurons in the terminal abdominal ganglia of small and large crayfish are similar in shape but differ in size according to an approximately isometric pattern of growth. The soma diameter of the large LG is 2.2 times larger than the small LG, the major ipsilateral dendrite is 2.8 times longer and 3.6 times greater in diameter, and the axon is 7.6 times longer and 4.5 times greater in diameter. The projected area of the major ipsilateral dendrite of LG in the horizontal plane of the terminal abdominal ganglion is 27 times larger in the large than in the small crayfish. 3. LG's input resistance was nearly 80% smaller in the large (167 K omega) than in the small (742 K omega) crayfish when measured at or near the initial axon segment. The cell's membrane time constant displayed an opposite relationship, with the value in the large crayfish (20.9 ms) nearly two-and-a half times larger than the value in the small crayfish (8.6 ms). 4. Simultaneous recordings were made from the distal portion of the ipsilateral dendrite and the initial axon segment of small and large LGs to determine how excitatory postsynaptic potentials (EPSPs) are attenuated or filtered by the electrotonic properties of the different sized cells. In the small LG, the fast alpha and the slower beta components of compound EPSPs evoked by sensory nerve stimulation were similarly attenuated. In the large LG, the alpha component of the compound EPSP was much more attenuated and smoothed than the slower beta component. 5. Multicompartment models of small and large LGs were constructed and used to test whether differences in the two neurons' physical properties could account for the differences in their passive response properties.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7983546 TI - Responses during eye movements of brain stem neurons that receive monosynaptic inhibition from the flocculus and ventral paraflocculus in monkeys. AB - 1. We have identified a group of brain stem cells called "flocculus target neurons" (or FTNs) because they are inhibited at monosynaptic latencies by stimulation of the flocculus and the ventral paraflocculus with single electrical pulses. We report the responses of FTNs, as well as those of other brain stem cells, during horizontal eye movements with the head stationary and during natural vestibular stimulation in monkeys. 2. FTNs discharged primarily in relation to eye movements. The majority (71%) showed increased firing for eye movement away from the side of the recording ("contraversive"), which is consistent with their inhibition by Purkinje cells that show increased firing for eye movement toward the side of recording. However, a significant and surprisingly large percentage (29%) of FTNs showed increased firing for eye movement toward the side of recording ("ipsiversive"). 3. The firing rate of FTNs showed strong modulation during pursuit of sinusoidal target motion with the head stationary and during the compensatory eye movements evoked by fixation of an earth-stationary target with sinusoidal head rotation. In addition, firing rate was related to eye position during steady fixation at different positions. Of the FTNs that showed increased firing for contraversive eye motion during pursuit with the head stationary, most had an infection in the relationship between firing rate and eye position so that the sensitivity to eye position was low for eye positions ipsilateral to straight-ahead gaze and high for eye positions contralateral to straight-ahead gaze. 4. When the monkey canceled the vestibuloocular reflex (VOR) by tracking a target that moved exactly with him during sinusoidal head rotation, the firing rate of FTNs was modulated much less strongly than during pursuit with the head stationary. In the FTNs that showed increased firing for contraversive eye motion during pursuit, firing rate during cancellation of the VOR increased for contraversive head motion during sinusoidal vestibular rotation at 0.4 Hz but was only weakly modulated during rotation at 0.2 Hz. 5. The position-vestibular-pause cells (PVP-cells), previously identified as interneurons in the disynaptic VOR pathways, were not inhibited by stimulation of the flocculus and ventral paraflocculus and had response properties that were different from FTNs. The majority (69%) showed increased firing for contraversive eye motion during pursuit and for ipsiversive head motion during cancellation of the VOR, whereas some (31%) showed the opposite direction preferences under both conditions.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7983547 TI - Neural basis for motor learning in the vestibuloocular reflex of primates. I. Changes in the responses of brain stem neurons. AB - 1. We recorded from neurons in the brain stem of monkeys before and after they had worn magnifying or miniaturizing spectacles to cause changes in the gain of the vestibuloocular reflex (VOR). The gain of the VOR was estimated as eye speed divided by head speed during passive horizontal head rotation in darkness. Electrical stimulation in the cerebellum was used to identify neurons that receive inhibition at monosynaptic latencies from the flocculus and ventral paraflocculus (flocculus target neurons or FTNs). Cells were studied during smooth pursuit eye movements with the head stationary, fixation of different positions, cancellation of the VOR, and the VOR evoked by rapid changes in head velocity. 2. FTNs were divided into two populations according to their responses during pursuit with the head stationary. The two groups showed increased firing during smooth eye motion toward the side of recording (Eye-ipsiversive or E-i) or away from the side of recording (Eye-contraversive or E-c). A higher percentage of FTNs showed increased firing rate for contraversive pursuit when the gain of the VOR was high (> or = 1.6) than when the gain of the VOR was low (< or = 0.4). 3. Changes in the gain of the VOR had a striking effect on the responses during the VOR for the FTNs that were E-c during pursuit with the head stationary. Firing rate increased during contraversive VOR eye movements when the gain of the VOR was high or normal and decreased during contraversive VOR eye movements when the gain of the VOR was low. Changes in the gain of the VOR caused smaller changes in the responses during the VOR of FTNs that were E-i during pursuit with the head stationary. We argue that motor learning in the VOR is the result of changes in the responses of individual FTNs. 4. The responses of E-i and E-c FTNS during cancellation of the VOR depended on the gain of the VOR. Responses tended to be in phase with contraversive head motion when the gain of the VOR was low and in phase with ipsiversive head motion when the gain of the VOR was high. Comparison of the effect of motor learning on the responses of FTNs during cancellation of the VOR with the results of similar experiments on horizontal gaze velocity Purkinje cells in the flocculus and ventral paraflocculus suggests that the brain stem vestibular inputs to FTNs are one site of motor learning in the VOR.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 7983548 TI - Neural basis for motor learning in the vestibuloocular reflex of primates. II. Changes in the responses of horizontal gaze velocity Purkinje cells in the cerebellar flocculus and ventral paraflocculus. AB - 1. We made extracellular recordings from Purkinje cells in the flocculus and ventral paraflocculus of awake monkeys before and after motor learning in the vestibuloocular reflex (VOR). Three samples were recorded 1) after miniaturizing spectacles had reduced the gain of the VOR (eye speed divided by head speed) to 0.4; 2) when the gain of the VOR was near 1.0; and 3) after magnifying spectacles had increased the gain of the VOR to 1.6. 2. We studied Purkinje cells that showed stronger modulation of simple-spike firing rate during horizontal than during vertical pursuit. These cells corresponded to the previously identified "horizontal gaze velocity Purkinje cells" or HGVP-cells. During pursuit of smooth target motion with the head stationary, HGVP-cells showed strong modulation of firing rate with increases for ipsiversive eye motion (toward the side of recording). When the monkey canceled his VOR by tracking a target that moved exactly with him during sinusoidal head rotation in the horizontal plane, HGVP cells again showed strong modulation of firing rate with increases for ipsiversive head motion. 3. The responses of HGVP-cells during pursuit with the head stationary and during cancellation of the VOR reveal separate components of firing rate related to eye and head velocity. We used these two behavioral conditions to test for effects of motor learning on the head and eye velocity components of the simple-spike firing of HGVP-cells. Our data confirm the previous observation that motor learning causes the sensitivity to head velocity to be larger when the gain of the VOR is high and smaller when the gain of the VOR is low. Thus we agree with the previous conclusion that changes in the vestibular sensitivity of HGVP-cells, measured during sinusoidal head motion at low frequencies, are in the wrong direction to cause changes in the gain of the VOR. 4. To determine whether the simple-spike output from the HGVP-cells plays a role in the VOR after motor learning, we recorded simple-spike firing during the VOR evoked by transient, rapid changes in head velocity in darkness. When the gain of the VOR was low, firing rate increased during the VOR evoked by ipsiversive head motion and decreased during the VOR evoked by contraversive head motion. When the gain of the VOR was high, the direction selectivity of the responses was reversed.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 7983549 TI - Neural basis for motor learning in the vestibuloocular reflex of primates. III. Computational and behavioral analysis of the sites of learning. AB - 1. We have used a combination of eye movement recordings and computer modeling to study long-term adaptive modification (motor learning) in the vestibuloocular reflex (VOR). The eye movement recordings place constraints on possible sites for motor learning. The computer model abides by these constraints, as well as constraints provided by data in previous papers, to formalize a new hypothesis about the sites of motor learning. The model was designed to reproduce as much of the existing neural and behavioral data as possible. 2. Motor learning was induced in monkeys by fitting them with spectacles that caused the gain of the VOR (eye speed divided by head speed) to increase to values > 1.6 or to decrease to values < 0.4. We elicited pursuit by providing ramp motion of a small target at 30 degrees/s along the horizontal axis. Changes in the gain of the VOR caused only small and inconsistent changes in the eye acceleration in the first 100 ms after the onset of pursuit and had no effect on the eye velocity during tracking of steady target motion. Electrical stimulation in the flocculus and ventral paraflocculus with single pulses or trains of pulses caused smooth eye movement toward the side of stimulation after latencies of 9-11 ms. Neither the latency, the peak eye velocity, nor the initial eye acceleration varied as a consistent function of the gain of the VOR. 3. The computer model contained nodes that represented position-vestibular-pause cells (PVP-cells) and flocculus target neurons (FTNs) in the vestibular nucleus, and horizontal gaze-velocity Purkinje cells (HGVP-cells) in the cerebellar flocculus and ventral paraflocculus. Node FTN represented only the "E-c FTNs," which show increased firing for eye motion away from the side of recording. The transfer functions in the model included dynamic elements (filters) as well as static elements (summing junctions, gain elements, and time delays). Except for the transfer functions that converted visual motion inputs into commands for smooth eye movement, the model was linear. 4. The performance of the model was determined both by computer simulation and, for the VOR in the dark, by analytic solution of linear equations. For simulation, we adjusted the parameters by hand to match the output of the model to the eye velocity of monkeys and to match the activity of the relevant nodes in the model to the firing of HGVP-cells, FTNs, and PVP-cells when the gain of the VOR was 0.4, 1.0, and 1.6.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 7983550 TI - Demonstration of HLA and ABH antigens in fresh and frozen human menisci by immunohistochemistry. AB - The expression of HLA and ABH antigens in fresh, frozen, and twice-frozen normal human meniscal tissue was evaluated with use of immunohistochemistry. A generalized expression of Class-I and Class-II HLA antigens was found in the endothelial and synovial cells of all three forms of tissue. Fibrochondrocytes were Class-I positive and Class-II negative. ABH antigens were expressed by endothelial cells in relationship to the blood group of the patient. Freezing preserved most of the HLA and ABH molecular structure. Although the normal meniscus consists of a relatively few chondrocytes embedded in an extracellular matrix, it also contains Class-II and ABH-positive endothelial cells and Class-II positive synovial cells. These antigens are present at the moment of transplantation and could evoke an immune response in the host that would modulate the results of meniscal allografting. PMID- 7983551 TI - Muscle pathology and clinical measures of disability in children with cerebral palsy. AB - We performed a histologic and morphometric study of spastic muscle from 10 children with diplegic cerebral palsy, comparing muscle structure with the gait parameters of energy expenditure index and dynamic electromyography. Variations in fiber area within and between fiber types were increased significantly in children with cerebral palsy. In each of the control subjects, the combined coefficient of variation for type-1 and type-2 fiber area was less than 25% and the average was 17%; in the subjects with cerebral palsy, the combined coefficient of variation was more than 25% and the average was 36% (p < or = 0.004). The average difference between the mean area of type-1 and type-2 fibers was 26.7 +/- 18.9% for subjects with cerebral palsy and 4.2 +/- 2.4% for control subjects (p < or = 0.004). There was a 67% predominance of one fiber type in the subjects with cerebral palsy compared with a 55% predominance in the control subjects (p < or = 0.03). The difference between the total area of type-1 and type-2 fibers was 57% in the subjects with cerebral palsy and 17% in the control subjects (p < or = 0.002). There was a significant correlation between the combined coefficient of variation of fiber area and the energy expenditure index (r = 0.77, p < or = 0.03). The difference between the mean area of type-1 and type-2 fibers correlated with prolongation of electromyographic activity (r = 0.69, p < or = 0.05). No abnormalities in fiber ultrastructure were found in the subjects with cerebral palsy. Children with cerebral palsy had abnormal variation in the size of muscle fibers and altered distribution of fiber types. The values for variation in fiber area correlated with the energy expenditure index and with prolongation of electromyographic activity during walking. PMID- 7983553 TI - Method for establishing and measuring in vivo forces in an anterior cruciate ligament composite graft: response to differing levels of load sharing in a goat model. AB - In order to determine the appropriate load history for optimal remodeling of an anterior cruciate ligament graft, methods for establishing and measuring the graft force due to an external load could be set to a preselected value in in vivo are required. Our objectives with this study were to (a) develop a method in which the graft force due to an external load could be set to a preselected value in a living animal, (b) show that this force could be maintained after fixation, and (c) determine what happens to the forces after the animal has functioned for as long as 2 weeks postoperatively, when differing levels of load sharing between the segments had been set at surgery. The anterior cruciate ligament was reconstructed in 12 goats with use of a bone-patellar tendon-bone graft and a synthetic augmentation device. The forces in the graft segments were established, at the time of surgical fixation, with use of a force-setting technique. In five animals, the tendon segment was set to carry 90% of the total graft force; in the remaining seven animals, the augmentation segment was set to share 90% of the total graft force. Graft forces were measured, with the use of buckle transducers mounted extra-articularly over the anterior tibia, under a 67 N anterior tibial load at 60 degrees of knee flexion before and after fixation and at 2 weeks postoperatively.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7983552 TI - Three-dimensional knee joint movements during a step-up: evaluation after anterior cruciate ligament rupture. AB - The three-dimensional motions of the knee were analysed during closed kinetic chain knee extension in 13 patients with unilateral chronic injury of the anterior cruciate ligament. The patients ascended a platform, and serial stereophotogrammetric roentgenograms were exposed from about 100 degrees of flexion to full extension. From a position of about 100 degrees of knee flexion and 20 degrees of internal rotation, the tibia rotated externally during the extension. Almost no tibial adduction or abduction was observed. The tibial intercondylar eminence translated laterally, distally, and anteriorly relative to the femur. In knees with absence of the anterior cruciate ligament, the intercondylar eminence had a more posterior position compared with the contralateral normal knees. The proximal tibia was used as a fixed reference segment to evaluate the anteroposterior translations of a central point in the femoral condyles. The femoral point was more anteriorly displaced in the injured than in the contralateral knees. This difference might reflect increased activity of the hamstrings in the injured knees, because it was most pronounced at 80 degrees of flexion and decreased with increasing extension. In the sagittal plane, the mean helical axis was positioned close to the femoral insertion of the ligament at 80 degrees of flexion and was displaced distally and anteriorly during extension. In the frontal plane, the axis had a transverse direction at 80 degrees of flexion. At close to full extension, the axis was positioned distally in the lateral condyle and proximally in the medial condyle. In the horizontal plane, the helical axes ran slightly more anteriorly in the medial than in the lateral femoral condyle but changed inclination at close to full extension and became almost parallel to the transverse axis. PMID- 7983554 TI - Determination of a zero strain reference for the anteromedial band of the anterior cruciate ligament. AB - The objective of this study was to verify a method previously used to determine a reference length for calculations of anterior cruciate ligament strain. In nine knee specimens, an arthroscopic force probe and a Hall effect transducer were placed in the anteromedial band of the ligament. Anteroposterior-directed shear loads then were applied to the knee joint with the knee flexed to 30 degrees. From the sigmoidal curve for shear load versus displacement of the anterior cruciate ligament midsubstance, the length of the transducer at the inflection point was determined graphically by two independent examiners. Previous studies suggested that the inflection point corresponds to the slack-taut transition of the anteromedial band. The force probe was used to determine the actual length of the transducer when the anteromedial band became load bearing. No significant differences were found between the reference lengths determined by the inflection point method and the force probe. The force probe demonstrated that the anterior cruciate ligament became load bearing when an anterior shear load of 8.8 N was applied to the tibia with the knee at 30 degrees of flexion. Furthermore, multiple cycles of anteroposterior shear loading did not influence these values. The force probe verified that the inflection method provides a reasonable estimate of the absolute strain reference (within 0.7% strain). PMID- 7983555 TI - Tensile and viscoelastic properties of human patellar tendon. AB - The tensile and viscoelastic properties of fresh-frozen, nonirradiated human patellar tendon were investigated in two groups of 15 specimens: one group was from individuals 29-50 years old and the other group was from individuals 64-93 years old. The central portion of each patella-patellar tendon-tibia complex was subjected to cyclic preconditioning, stress-relaxation, cyclic stress-relaxation, and load to failure tests. For each age group, stress-relaxation and stress strain curves were obtained, from which percentage relaxation, ultimate tensile strength, strain at failure, modulus, and strain energy density were determined. Viscoelastic behavior was described with use of quasilinear viscoelasticity. The younger group showed a 46 +/- 9% (mean +/- SD) decrease in stress after 15 minutes, whereas the older group exhibited a 50 +/- 6% decrease. The values for ultimate tensile strength and strain at failure, respectively, were 64.7 +/- 15.0 MPa and 14 +/- 6% for the younger group and 53.6 +/- 10.0 MPa and 15 +/- 5% for the older group. Modulus values were 660 +/- 266 MPa for the younger group and 504 +/- 222 MPa for the older group. Except for ultimate tensile strength, which was 17% less for the older group than for the younger one, no statistically significant differences were found in tensile or viscoelastic properties. This study indicated that there were minimal differences in biomechanical properties of the substance of the patellar tendon between younger and older age groups. PMID- 7983556 TI - Compressive stress-relaxation behavior of bovine growth plate may be described by the nonlinear biphasic theory. AB - The compressive behavior of the bovine distal femoral growth plate was studied in vitro. Strain-rate controlled, compression stress-relaxation experiments were performed on cylindrical bone-growth plate-bone specimens from the interior and periphery of the growth plate. The questions addressed in this study were (a) Can the nonlinear biphasic theory, one with strain-dependent permeability, be used to represent the compressive stress-relaxation behavior of bovine growth plate? (b) How do different assumptions concerning the permeabilities of the chondro-osseous interfaces influence the inferred material properties of the growth plate? and (c) Are there any differences in these properties between the periphery and the interior of the growth plate? Intrinsic biphasic material properties--aggregate modulus (HA), Poisson's ratio (v), and nonlinear strain-dependent permeability coefficients (ko and M)--were calculated from the compression stress-relaxation data with use of a finite element model and a least squares curve-fitting procedure. To verify this constitutive model for the growth plate, an independent set of finite element analyses was performed with use of the determined intrinsic biphasic properties, and comparisons were made between these finite element predictions and two additional sets of experimental data subsequently obtained for the same specimens with use of two slower rates of compression. Excellent agreement was achieved between these finite element predictions and the latter two sets of data. The aggregate modulus was found to be insensitive to the permeability of the chondro-osseous interface. The permeability coefficients were very sensitive to, and the Poisson's ratio was only slightly sensitive to the interface permeability condition. Therefore, the periphery of the growth plate is more compliant and permeable than the interior. PMID- 7983557 TI - Tendons attached to prostheses by tendon-bone block fixation: an experimental study in dogs. AB - To develop a method of tendon attachment to a metallic endoprosthesis, we evaluated fixation strength, clinical function of the tendon, and morphological changes in an experimental model. The canine supraspinatus tendon was removed from the greater tubercle of the humerus and attached to a titanium prosthesis. In 12 animals, the bone block underlying the tendon insertion was preserved and attached in one limb; the soft part of the tendon was attached directly to the prosthesis in the contralateral limb. Fixation strength was evaluated after 16 weeks of in vivo implantation (12 specimens) and compared with the in vitro fixation strength (12 specimens) and with intact normal controls (six specimens from cadavera). Function of the tendon in vivo was evaluated by force-plate analysis (at 3-week intervals). All specimens were evaluated histologically. Sixteen weeks after surgery, the tendon-bone block attachment was significantly stronger (mean, 16%) than the direct tendon attachment and not significantly different from the normal control, and the direct tendon attachment was significantly weaker (mean, 68%) than the normal control. There was significantly more weight-bearing on the limbs with a tendon-bone block attachment than on the limbs with a direct tendon attachment at both 3 and 6 weeks postoperatively. Both front legs showed increased weight-bearing with time, but the differences were not statistically significant. Anchorage by tissue ingrowth to the titanium prosthesis was found consistently--there was bone ingrowth in the tendon-bone block attachments and fibrous tissue ingrowth in the direct tendon attachments. When a bone block was preserved, the strength and stiffness were comparable with those of a normal tendon insertion.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7983559 TI - Mechanical evaluation of six types of reconstruction following 25, 50, and 75% resection of the proximal femur. AB - The structural stiffness and the stiffness of the osteotomy site after six types of reconstruction of the proximal femur were compared by testing in axial compression, mediolateral bending, and axial torsion in a canine model. An osteotomy was carried out for 25, 50, or 75% of the length of each femur, and the proximal portion was replaced by one of five allograft/endoprosthetic composites or a segmental replacement. The reconstructions included (a) a composite press fit proximally and cemented distally, (b) a composite cemented proximally and distally, (c) a composite cemented proximally and fixed with two plates at the allograft-host bone interface, (d) a composite cemented proximally and secured distally with bicortical screws, (e) a composite secured proximally and distally with bicortical screws, and (f) a segmental prosthesis cemented into the distal femur. The results showed that the segmental reconstruction and the reconstruction with double-plate fixation and a cemented endoprosthesis were structurally stiffer and had greater stiffness of the osteotomy site than the other reconstructions. In comparison, reconstructions that involved cement alone or cement and press-fit techniques generally were more compliant than the others, both structurally and at the osteotomy site. PMID- 7983558 TI - Estimation of material properties in the equine metacarpus with use of quantitative computed tomography. AB - The purpose of this study was to investigate the relationships between data obtained from quantitative computed tomography and mechanical properties in the equine metacarpus, as measured in vitro in bone specimens. Three hundred and fifty-five bone specimens from the metacarpi of 10 horses were machined into right cylinders aligned with the long axis of the bone. A computed tomographic scan of the specimens, along with a Cann-Genant K2HPO4 calibration standard, was obtained. The specimens then were compressed to failure, and the elastic modulus, yield stress, yield strain, strain energy density at yield, ultimate stress, ultimate strain, and strain energy density at ultimate failure were calculated. The specimens were dried and ashed. Quantitative computed tomography-derived K2HPO4 equivalent density proved to be an excellent estimator (r2 > 0.9) of elastic modulus, yield stress, ultimate stress, wet density, dry density, and ash density; a moderately good estimator (0.4 < r2 < 0.9) of strain energy density at yield and at ultimate failure; and a poor estimator (r2 < 0.2) of yield strain and ultimate strain. It was concluded that the relationships between quantitative computed tomography data and mechanical properties of the equine metacarpus were strong enough to justify the use of these data in automated finite element modeling. PMID- 7983561 TI - Superior displacement of the hip in total joint replacement: effects of prosthetic neck length, neck-stem angle, and anteversion angle on the moment generating capacity of the muscles. AB - The purpose of this study was to determine the effects of superior displacement of the hip center and changes in three prosthetic parameters (neck length, neck stem angle, and anteversion angle) on the capacity of muscles to generate force and moment about the hip. A three-dimensional model that calculates the maximum isometric forces and moments generated by 25 muscles crossing the hip over a wide range of body positions was used to evaluate the effects of a 2 cm elevation of the hip center and changes in the prosthetic parameters. After superior displacement of the hip center, the neck length was increased from 0 to 3 cm, the neck-stem angle was varied between 110 and 150 degrees, and the anteversion angle was varied between 0 and 40 degrees. Our analysis showed that a 2 cm superior displacement of the hip center would decrease the moment-generating capacity of the four muscle groups studied (abductors, adductors, flexors, and extensors) if neck length were not increased to compensate for decreased muscle length. In the computer model of an adult man that we used, a 2 cm increase in neck length restored the moment-generating capacity of the muscles by increasing muscle length and force-generating capacity. However, a 3 cm increase in neck length increased passive muscle forces substantially, which potentially could limit joint motion. An increased neck-stem angle (i.e. a valgus neck) decreased the abduction moment arm but increased the moment-generating capacity of the other muscle groups. A change in the anteversion angle from 0 to 40 degrees had a relatively small effect on the isometric moment-generating capacity of the muscles studied. PMID- 7983560 TI - Systemic immune response to peripheral nerve transplants across major histocompatibility class-I and class-II barriers. AB - The use of peripheral nerve transplantation in limb reconstruction has been limited by tissue rejection. In order to identify the major histocompatibility antigens involved in tissue rejection, mutant strains of inbred mice, differing from the parent strain (C57BL/6) by either major histocompatibility complex Class I (B6.C-H2bml mice) or Class II (B6.C-H2bml2 mice), were used in models of nerve transplantation. One, 2, and 3 weeks after nerve or skin transplantation, the immune response in the recipient animal was monitored with use of lymphocyte dependent cytotoxicity and complement-dependent cytotoxicity assays. Skin transplants were used for comparison as the gold standard of a nonvascularized graft with an easily observable success or failure. There was no significant cellular immune response by the lymphocyte-mediated cytotoxicity assay when nerve or skin transplants involved an isolated Class-I or Class-II mismatch, but there was a significant response 2 weeks after transplantations across a combined Class I and Class-II barrier for nerve (p < 0.04) or skin (p < 0.03). An antibody response to the grafts occurred for both skin and nerve transplants but only when a combined barrier was involved. This preliminary study, using a mouse model, suggests that nerve transplantation-may be performed without systemic evidence of rejection with only a partial cross match of the major histocompatibility complexes, thus decreasing the complexity of tissue typing necessary for tissue banking. PMID- 7983562 TI - Effects of cis-diamminedichloroplatinum II released from D,L-polylactic acid implanted adjacent to cortical allografts in dogs. AB - This study was performed to determine the pharmacokinetics and local and systemic effects of cis-diamminedichloroplatinum II (cisplatin) released from an open-cell polylactic acid polymer when the drug delivery device was placed adjacent to a cortical allograft. Bilateral intercalary femoral allografts were implanted in six normal beagles. The polymer containing cisplatin was implanted adjacent to the allograft in one femur, and the polymer without cisplatin was implanted adjacent to the allograft in the contralateral femur. Systemic toxicity was evaluated clinically by hematologic and serum biochemistry tests and urinalysis. Healing of the allograft was monitored radiographically. The femora were evaluated biomechanically, histologically, and histomorphometrically 7.5 months after surgery. Total serum platinum levels were measured by atomic absorption spectrophotometry, and pharmacokinetic parameters were calculated. Healing was impaired slightly by the presence of the polymer with cisplatin, and systemic and local toxicity was mild and transient. After implantation of the polymer with cisplatin, the mean peak total serum platinum concentration was low (1.71 +/- 0.19 micrograms/ml). However, the area under the curve for total serum platinum concentration versus time for the first 21 days was large (27,050 +/- 3,201 micrograms.min/ml). When cisplatin was given as an intravenous bolus at a dose of 70 mg/m2 to six other beagles, the mean peak total platinum concentration was 8.80 +/- 2.1 micrograms/ml and the area under the curve was 940.3 +/- 256.7 micrograms.min/ml. These results indicate that a sustained release of cisplatin can be delivered safely from an open-cell polylactic acid polymer. This device may be useful in the treatment of solid tumors. PMID- 7983563 TI - Ion resonance electromagnetic field stimulation of fracture healing in rabbits with a fibular ostectomy. AB - Rabbits with a fibular ostectomy were exposed for 28 days to magnetic fields that satisfied the ion resonance conditions for calcium or magnesium. The rabbits were exposed to whole body treatment for 1/2 hour, 3 hours, or 24 hours per day. The fibulae from the experimental and control animals were removed surgically and were subjected to force-deflection testing to establish the stiffness of the healed fracture. The fibulae from the rabbits exposed to the ion resonance magnetic fields were found to be 55-299% (p < 0.01) more robust than the fibulae from the control animals. PMID- 7983564 TI - Gastroesophageal reflux: one reason why baby won't eat. AB - Gastroesophageal reflux (GER) is the movement of gastric contents retrograde into the esophagus. Sometimes the refluxate is seen as emesis, but often reflux is "silent," meaning that there are no discrete symptoms during an episode. In adults, the most common symptom of GER is heartburn, whereas in infancy excessive crying and malaise are symptoms that prompt investigation for GER, with or without esophagitis. Symptoms of esophagitis in infancy may include arching (hyperextension) of the torso and refusal of feedings. Tube feedings may be required to treat infants with failure to thrive who refuse oral feedings. Paradoxically, tube feedings increase the number of GER episodes. A hypothetical explanation for refusal of food in infancy is that pain with swallowing (odynophagia) or heartburn are consequences of peptic esophagitis. As a result, infants will learn to refuse food if it hurts or if they fear that it will hurt to eat. Another possible mechanism is visceral hyperalgesia, a neuropathic condition in which prior experience changes sensory nerves so that previously innocuous stimuli are perceived as painful. Some infants may have especially sensitive sensory nerves in the upper gastrointestinal tract, which predisposes visceral hyperalgesia to develop. Thus pain occurs from luminal distension or acid reflux in the absence of tissue damage. The evaluation of babies who won't eat includes a careful history and physical examination to exclude the possibility of chronic systemic illness. Refusal to feed is an unusual manifestation of a common condition: GER disease. The initial tests for GER usually include a barium swallow study to assess the upper gastrointestinal anatomy, endoscopy and esophageal biopsy to assess esophagitis, and an intraesophageal pH study, which is useful in "silent" reflux to quantitate the duration of esophageal acid exposure and to correlate discrete symptom episodes with periods of reflux. The treatment of infants and toddlers who refuse to eat because of pain resulting from visceral hyperalgesia or reflux esophagitis involves removing the pain associated with eating and making eating a pleasurable experience. Treatment for esophagitis may include maintaining an upright posture after meals and thickened feeds, medication to improve gastrointestinal motility or to decrease acid secretion, or fundoplication. PMID- 7983565 TI - Munchausen by proxy syndrome: a modern pediatric challenge. AB - Munchausen by proxy syndrome is a condition in which a mother pretends her infant or child is ill or causes the infant or child to be ill in order to engage in an intensely ambivalent but often destructive relationships with a physician. Despite appearances to the contrary, evidence indicates that the infant serves as little more than an object to regulate this relationship. The harming of the child takes place in a fully conscious nonpsychotic state and is a by-product of the dynamics of this relationship. We see the mother's actions as an example of imposturing good mothering. Physicians are susceptible to these mothers in ways that lead them to delays in uncovering these dynamics that can have disastrous consequences for the infant. Social and interpersonal forces that contribute to the unfolding of this syndrome are worthy of our study. PMID- 7983566 TI - Feeding disorders in infants and children. PMID- 7983567 TI - Functional vomiting disorders in infancy: innocent vomiting, nervous vomiting, and infant rumination syndrome. AB - Pediatric gastroenterologists have tended to view gastroesophageal reflux (GER) as a disease in and of itself--a disease that can be diagnosed "objectively" with use of numerical data from esophageal pH monitoring and cured with pharmacologic or surgical treatment. What is often forgotten is that the data derived from esophageal pH monitoring and other techniques may identify the presence of abnormal GER but tell nothing about its pathogenesis. The usual approach to infants who feed poorly, vomit, or fail to gain weight is to identify the presence of abnormal GER, rule out underlying organic causes of vomiting, and then diagnosis primary GER disease. The baby is then treated with pharmacologic, dietary, or positional therapy and, ultimately, if these therapies fail to eradicate the symptoms attributed to GER, surgical fundoplication, which stops vomiting regardless of its causes. The pediatric literature on infant vomiting and GER is almost devoid of research into the nature and possible relationships among infant stress, vomiting, feeding difficulties, and failure to grow. Clinically, the quality of the maternal-infant relationship is frequently approached superficially, with psychosocial aspects treated as less important in infants considered to have primary organic disease amenable to medical or surgical treatment. Psychosocial factors in the pathogenesis of the infant's symptoms are often not pursued beyond assessment for possible abuse or neglect. It has been known for centuries that stress or excitement affects gastrointestinal function and symptoms. Although the field of infant psychiatry has produced a substantial literature on the nature of stresses that affect both infants and mothers, the pediatric literature on vomiting and failure to thrive seldom acknowledges the existence or importance of these contributions. In clinical practice, failure to explore psychosocial aspects that may contribute to vomiting, feeding difficulties, or failure to thrive may result in missed opportunities for less invasive, more effective therapy at best, and countertherapeutic treatment at worst. This article describes three functional vomiting disorders of infancy, their distinguishing characteristics, hypotheses regarding their pathogenesis, and principles of comprehensive management. PMID- 7983568 TI - Visceral pain in infants. AB - Visceral pain in infants represents a complexity of interacting neural, developmental, psychosocial, and environmental factors, which must be separately and conjointly evaluated. Inhibitory mechanisms are not fully developed in infants and thus nociception is not readily dampened. Heightened behavioral responses to pain (e.g., crying) are likewise not easily inhibited. Esophageal pain and behaviors perceived by the caregiver to represent pain (e.g., crying and retching) can potentially affect normal growth and development. The response of the infant to pain and other visceral sensory stimuli and the ability to cope with these sensations (painful and nonpainful) are shaped by the relationship of the infant with the primary caregiver, usually the mother. Neural mechanisms of pain transmission and inhibition are reviewed, as well as biopsychosocial and environmental characteristics that can shape or contribute to infant pain syndromes. Proposed multifaceted clinical treatment strategies are aimed at decreasing efforts to dampen excitatory neural sensory signaling and improving the mother/infant relationship and maternal behavioral response to the crying infant. PMID- 7983569 TI - Mycotic keratitis--an underestimated mycosis. AB - Mycotic keratitis, an important ophthalmologic problem, especially in outdoor workers in the tropics, is frequently caused by filamentous fungi such as species of Fusarium, Aspergillus and Curvularia, and by yeast-like fungi such as Candida. A rapid, presumptive diagnosis can be made by recognition of certain typical clinical features and by direct microscopic detection of fungi in corneal scrapings stained by various methods. The diagnosis is confirmed by culture. In difficult cases, microbiological studies on corneal biopsies or histopathological studies on tissue sections may need to be performed. The use of fluorescein conjugated lectins and similar diagnostic tools is aimed at providing rapid, species-specific detection of fungi in corneal tissue. Antifungal therapy must be instituted as soon as the diagnosis is made. While keratitis due to Aspergillus, Candida and dematiaceous fungi can be successfully treated by many of the currently available polyenes and azoles, the treatment of Fusarium keratitis still frequently requires the use of pimaricin or econazole. Treatment by the oral and parenteral routes may prove useful in severe mycotic keratitis. Surgery may need to be performed on cases unresponsive to medical therapy or where serious complications are likely to occur. The pathogenesis of mycotic keratitis appears to involve agent factors, such as invasiveness and toxigenicity, and host factors, such as trauma and intrinsic defects in resistance. Areas for future research include the development of rapid, species-specific diagnostic aids, of broad-spectrum antifungal compounds active by various routes, and of therapeutic modalities which act on the fungus and on molecules involved in the pathogenesis of the condition. PMID- 7983570 TI - Acid proteinase secreted by Candida tropicalis: virulence in mice of a proteinase negative mutant. AB - The relationship between the ability to secrete a specific acid proteinase (ACP) by Candida tropicalis in the presence of bovine serum albumin as a nitrogen source and virulence for mice was studied using two stable proteinase-positive and proteinase-negative strains (DSY68 and DSY65), which were constructed from the wild-type pathogenic yeast C. tropicalis ATCC 750. The inactivation of the gene encoding the secreted acid proteinase was produced by targeted gene disruption. Mortality rate was slightly lower in groups of mice infected with the proteinase-negative mutant. All other parameters analysed were similar for two strains of yeast. Our results therefore conclude that the ACP secreted by C. tropicalis did not contribute significantly to fungal virulence in systemic infections. PMID- 7983571 TI - Comparative in vitro activity of antimycotic agents against pathogenic vaginal yeast isolates. AB - Although numerous antimycotic agents are available for the treatment of yeast vaginitis there is little comparative data on the in vitro activity of these drugs. In the present two-part study, in vitro macro-broth dilution sensitivity tests were performed on a total of 377 clinical vaginal yeast isolates of nine different species. Antimycotics surveyed included amphotericin B, 5 fluorocytosine and eight azole derivatives. Results show that all vaginal Candida albicans isolates were uniformly sensitive at low concentration to all 10 antimycotics tested. However, non-albicans species, especially Candida glabrata and Saccharomyces cerevisiae, manifested several-fold increases in minimal inhibitory concentrations to all azoles tested except butoconazole. In particular, the in vitro potency of fluconazole and terconazole against species other than C. albicans was relatively poor, whereas the drugs demonstrating the best activity were itraconazole, butoconazole and saperconazole. Susceptibility testing of vaginal C. albicans isolates is not routinely indicated, even in patients with recurrent vaginitis and should be reserved for selected organisms, especially non-albicans species, in patients with clinical failure only. PMID- 7983572 TI - New records of nail and skin infection due to Onychocola canadensis and description of its teleomorph Arachnomyces nodosetosus sp. nov. AB - Non-dermatophytic fungi are increasingly being recognized as agents of onychomycosis. In 1990, three cases of chronic infection of the great toenail in adult female residents of Canada were attributed to Onychocola canadensis, a previously unknown hyphomycete. Three additional cases were suspicious but unconfirmed. This report documents seven new records, including six of toenail infection in elderly individuals and one case of glabrous skin infection. Three isolations from New Zealand represent the first report of O. canadensis outside Canada. Treatment with griseofulvin in one New Zealand hallux infection case was found to improve the appearance of the nail, but specimens were culture positive after 6 months. The development in culture of broad, brown, nodose, thick-walled hyphae suggested an affinity to the ascomycete genus Arachnomyces. Although mating experiments were attempted on several different media, ascocarps were produced in six mated pairs on sterilized rice grains or rice extract agar after 7-12 months incubation. Arachnomyces nodosetosus Sigler & Abbott sp. nov. is described and compared with Arachnomyces minimus Malloch & Cain, also rarely isolated from cutaneous specimens. The genus Arachnomyces is placed in the Gymnoascaceae (Onygenales). PMID- 7983573 TI - Regulation of phase-specific genes in the more general switching system of Candida albicans strain 3153A. AB - It was previously demonstrated that the genes PEP1 and Op4 are selectively transcribed in the opaque phase of the white-opaque transition in Candida albicans strain WO-1, and that the gene Wh11 is selectively transcribed in the white phase. However, the white-opaque transition occurs in only a minority of C. albicans strains and the opaque cell phenotype is highly specialized. To test whether these genes are regulated in more mainstream switching systems in C. albicans, their expression was analysed in the switching system of the laboratory strain 3153A. Both PEP1 and Op4 are not expressed in the basic smooth phenotype of 3153A, but they are expressed in switch phenotypes. However, expression is dissociated. Op4 is expressed in irregular wrinkle, star and revertant-smooth cells, while PEP1 is expressed only in star cells. Wh11 is expressed in the basic smooth and three tested variant phenotypes and is again associated with growth in a round budding form. The results support the general conclusion that PEP1 and Op4 are under the strict regulation of switching in C. albicans. PMID- 7983574 TI - Comparison of the metal-binding anticandidal activities of serum and abscess fluid supernatants. AB - Serum transferrin appears to play a role in host defense by competing with invading microorganisms for iron. The purpose of the present study was to compare this activity to a similar one recently described in abscess fluids and based on a calcium- and zinc-binding protein called calprotectin. Serum and abscess fluid supernatants were collected and pooled from groups of five to 10 C57BL/6 mice with experimental Candida albicans abscesses; serum was also collected from normal animals. In four experiments, serum was found to reduce in vitro C. albicans growth in Sabouraud glucose broth by a mean of 97.9% at 10 mg ml-1 of protein; this effect was reversed by adding 3-10 microM FeCl3, but not by similar amounts of ZnSO4. Abscess fluid supernatants had a greater effect, reducing growth by 99.9% at 1 mg ml-1 and 76.1% at 0.1 mg ml-1 of total protein; this effect was reversed by 3-10 microM ZnSO4, but not FeCl3. Although abscess fluid supernatants were effective when high inocula (10,000 yeast cells) were used, serum from the infected mice inhibited growth only with lower inocula (10-100 yeast cells). In a separate study, serum from infected mice (eight pools) reduced growth (by a range of 36 to 97%), whereas serum from normal mice (five pools) actually enhanced growth in this system (by a range of 173 to 595%).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7983575 TI - Melanin-deficient mutants of Cryptococcus neoformans. AB - Cryptococcus neoformans is a significant fungal pathogen in immunocompromised patients. The ability of C. neoformans to produce melanin has been correlated with virulence. The role of melanin in promoting virulence is unclear, although an anti-oxidant function has been suggested. To begin to define the genetic mechanisms responsible for melanin production in C. neoformans, we describe the isolation of seven melanin-deficient mutant classes. Some of the mutants can be suppressed by addition of Cu2+ to media, suggesting that the phenoloxidase of C. neoformans, like other fungal phenoloxidases, contains copper. Other mutants display a recessive sterile phenotype. A genetic and phenotypic characterisation of these mutants is presented. PMID- 7983576 TI - Cryptococcus neoformans vertebral osteomyelitis. AB - A 67-year-old previously healthy woman presented with low back pain of 2 months duration and daily fever of 39 degrees C for 3 weeks. CT scan showed a lytic lesion in the third lumbar vertebra and a small right lower lobe lung infiltrate with mediastinal lymphadenopathy. Culture of material obtained from open biopsy of the vertebra grew Cryptococcus neoformans var. neoformans, which was also demonstrated on histology. Cryptococcal antigen was detected in the patient's serum. Treatment with amphotericin B (1000 mg total dose) and oral 5 fluorocytosine, resulted in complete recovery and resolution of the chest X-ray findings with a follow-up of 2 years. Since this case, as well as most of the previously described cases of cryptococcal osteomyelitis, were in normal hosts, cryptococcal osteomyelitis should be considered in the differential diagnosis even in a normal host, and therefore, prior to possible invasive diagnostic procedures, cryptococcal antigen in the serum should be determined. PMID- 7983577 TI - Dematiaceous--a mycologic misnomer? AB - The term dematiaceous has been used to describe dark fungi. However, the historic and etymologic derivation suggest that the concept of dark coloration attached to the root demat... is epistemologically incorrect. PMID- 7983579 TI - Race of source effects in the elaboration likelihood model. AB - In a series of experiments, we investigated the effect of race of source on persuasive communications in the Elaboration Likelihood Model (R.E. Petty & J.T. Cacioppo, 1981, 1986). In Experiment 1, we found no evidence that White participants responded to a Black source as a simple negative cue. Experiment 2 suggested the possibility that exposure to a Black source led to low-involvement message processing. In Experiments 3 and 4, a distraction paradigm was used to test this possibility, and it was found that participants under low involvement were highly motivated to process a message presented by a Black source. In Experiment 5, we found that attitudes toward the source's ethnic group, rather than violations of expectancies, accounted for this processing effect. Taken together, the results of these experiments are consistent with S.L. Gaertner and J.F. Dovidio's (1986) theory of aversive racism, which suggests that Whites, because of a combination of egalitarian values and underlying negative racial attitudes, are very concerned about not appearing unfavorable toward Blacks, leading them to be highly motivated to process messages presented by a source from this group. PMID- 7983580 TI - An examination of the complementarity of interpersonal behavior. AB - The complementarity of behavior as moderated by the base rates of consequent behaviors, the differences attributable to friendly and hostile antecedent behaviors, and octant versus quadrant codes was examined. Complementarity was defined using 3 different but overlapping models: R. Carson (1969), D. Kiesler (1983), and J. Wiggins (1979). The Interpersonal Communication Rating Scale (ICRS; S. Strong & Hills, 1986) behavioral ratings on 80 female dyads provided by Strong, Hills, Kilmartin, et al. (1988) were analyzed using the randomization test of hypothesized order relations and correspondence analysis. Results demonstrated that (a) complementarity was supported for each of the 3 definitions (Carson's, Kiesler's, and Wiggins's), (b) complementarity fit the data better if account was taken of the base rate of behavior, (c) complementarity was more prominent if the antecedent behavior was friendly rather than hostile, and (d) complementarity of quadrant behavior was fairly strong. Results are discussed with respect to the measurement of interpersonal behaviors and the construct of complementarity. PMID- 7983578 TI - Utility of the triazole D0870 in the treatment of experimental systemic coccidioidomycosis. AB - The new triazole, D0870, was tested for therapeutic efficacy in the treatment of experimental systemic murine coccidioidomycosis. D0870 at 1 or 10 mg kg-1 daily, or 10 or 100 mg kg-1 every other day, and fluconazole at 100 mg kg-1 daily prolonged survival (P < 0.01), but were equivalent to each other. D0870 at 10 mg kg-1 daily or 100 mg kg-1 every other day cured 20 or 30% of mice of residual infection, respectively, and were superior to 100 mg kg-1 of fluconazole daily (P < 0.001). D0870 is approximately 10-fold more active than fluconazole. It is a promising treatment for coccidioidomycosis, which warrants further testing. PMID- 7983581 TI - Relating the Tellegen and five-factor models of personality structure. AB - With 575 college students, the relationship between A. Tellegen's (1985) personality model, assessed with the Multidimensional Personality Questionnaire (MPQ), and the Big Five model, operationalized by Costa and McCrae's (1985) NEO Personality Inventory, was investigated. Correlations and joint factor analyses indicated that the MPQ constructs could be well-organized under the Big Five model, and the NEO constructs could be well-organized under the Tellegen higher order dimensions (plus Absorption). Tellegen's higher-order dimensions relate to components of the Big Five hierarchically: Negative Emotionality encompasses Big Five Neuroticism and Agreeableness, Positive Emotionality encompasses Extraversion and the surgent aspect of Conscientiousness, and Constraint encompasses the controlled aspect of Conscientiousness and much of Openness to Experience. PMID- 7983582 TI - Self-regulation of mood: strategies for changing a bad mood, raising energy, and reducing tension. AB - Four studies evaluated the success of behaviors and strategies used to self regulate bad moods, raise energy, and reduce tension. Study 1 (N = 102) used an open-ended questionnaire to identify behavioral categories. Studies 2 and 4 surveyed a representative sample (N = 308) with a fixed-response questionnaire to quantify behaviors, general strategies, and individual differences. Study 3 used psychotherapist (N = 26) judgments of the likely success of the strategies. Therapist and self-rating converged on success of strategies and gender differences. These studies clarify and confirm previous research findings, particularly gender differences in controlling depression. Exercise appears to be the most effective mood-regulating behavior, and the best general strategy to change a bad mood is a combination of relaxation, stress management, cognitive, and exercise techniques. Results support a 2-dimensional biopsychological model of mood. PMID- 7983583 TI - Desire for control, felt control, and stress inoculation training during dental treatment. AB - Coping style research has typically assessed subjects' desire for a coping resource, but ignored whether subjects possess that resource. In this study 110 dental patients were categorized as to their desire for and feelings of control and were randomly assigned, just prior to dental treatment, to a 20-minute Stress Inoculation Training (SIT) session or a Filler condition. SIT significantly reduced pain and increased control only for patients who initially reported a high desire for control coupled with low perceived control. This finding supports the view that the discrepancy between high desire for control and low perceived control plays a causal role in the elevated distress and pain initially reported by patients with such control perceptions. These data indicate that consideration of patients' perceived coping resources as well as their coping preferences adds to our ability to predict reactions to stress reduction manipulations. PMID- 7983584 TI - Adaptive transparent film dressings. AB - Transparent film dressings have many of the attributes of the ideal wound dressing. However, currently available film dressings are deficient in their ability to handle varying levels of wound exudate. The permeability of polymeric films to water vapor is discussed and techniques are described to produce films in which the moisture vapor permeability is a function of the moisture in the environment. Illustrations are provided showing the variation of permeability with relative humidity and water contact. The unique properties of coextruded films are illustrated and the responsiveness of such a film dressing to varying conditions at the wound are discussed. PMID- 7983585 TI - Histological assessment of sintered metal-fibre-web materials. AB - Recently it has been shown that flexible metal fibre mesh structures can be used for the subcutaneous stabilisation of percutaneous devices. However, for the safe application of fibre mesh structures, it is necessary that these materials possess certain biological properties. The purpose of this paper is to discuss surgical, statistical and histological methods for the testing and evaluation of metal fibre web materials for soft tissue application. The use and potential of the described techniques are demonstrated with two examples. PMID- 7983586 TI - In vitro evaluation of the antimicrobial efficacy and biocompatibility of a silver-coated central venous catheter. AB - Central venous catheter infection presents an important problem in modern medicine, leading sometimes to a life-threatening situation for the patient as well as contributing to prolonged hospital stay and to an increase in costs. We have evaluated the in vitro biocompatibility and antimicrobial activity of a silver-coated polyurethane catheter designed for use as a colonization-resistant, antiinfective catheter. Due to a comparatively low silver release, the catheter performed well in cell toxicity and blood compatibility tests as well as in acute toxicity tests done with mice. The antimicrobial activity was tested in stationary and dynamic bacterial adherence experiments using S. epidermidis, E. coli and P. aeruginosa as test strains. The silver-coated polyurethane catheter showed good ability to prevent microbial colonization of the catheter surface. Currently a clinical trial of the silver-coated catheter is under investigation. PMID- 7983587 TI - Biocompatible polyurethane-based hydrogel. AB - A polyurethane polymer developed at W. R. Grace has been evaluated for a variety of biomedical applications. The primary property of the polymer exploited for these applications is its ability to prevent protein adsorption when coated on a surface. The prepolymer consists of a trifunctional poly(ethyleneoxide-propylene oxide) triol end capped with isophorone diisocyanate. The prepolymer is reactive with water and can be converted to a hydrogel, a thin coating, or a soluble conjugate with another compound. Each category lends itself to separate biomedical applications which are described in detail. The non-toxic nature of the polymer was demonstrated in a number of systems and suggests its utility in biomedical applications. PMID- 7983588 TI - Alkali halide-assisted penetration of neostigmine across excised human skin: a combination of structured water disruption and a Donnan-like effect. AB - The penetration of neostigmine across excised human skin mounted in flow-through diffusion cells, delivered from a 0.28 M aqueous solution, was below detection limits. The presence of either NaCl or LiCl in the donor solution caused significant fluxes of neostigmine, with permeability coefficients (Kp's) in the range of 10(-6) cm min-1. Paradoxically, low concentrations of NaCl or LiCl (0.25 and 0.5 M) were more effective in this respect than the 1 M solution, which was the least effective concentration in the range of 0.25-3 M. Thus, the dependence of the experimental Kp values on inorganic ion concentration followed a biphasic course, suggesting the participation of two distinctive mechanisms in the penetration-enhancement process. The early phase corresponding to 0.25 and 0.5 M NaCl or LiCl is being partly ascribed to a decrease in the viscosity of lamellar water caused by the influx of the respective hydrated ions, hydration of LiCl or NaCl being more extensive at low alkali halide concentration that at higher ones (reference cited). The late phase corresponding to 2 and 3 M LiCl and NaCl is partly ascribed to a Donnan-like effect whereby the presence of a large excess of poorly diffusible common ion (Na+ or Li+) enhances the partitioning into the skin of the more diffusible ion, in this case neostigmine cation. The presence of inorganic ions at different concentrations had no effect on the partial molal volume of neostigmine bromide (Vi infinity = 223.5 cm3 mol-1), which was practically the same for all concentrations of either LiCl and NaCl.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7983589 TI - Dose-dependency of flurbiprofen enantiomer pharmacokinetics in the rat. AB - Flurbiprofen is a chiral 2-arylpropionate used clinically as a racemate. Previously a significant pharmacokinetic interaction between the enantiomers of flurbiprofen has been reported in both rats and humans. The possible mechanism for this interaction was believed to involve competitive protein binding between the enantiomers. In addition, the saturable binding of flurbiprofen enantiomers in vitro in human plasma has been demonstrated. In this study different doses of racemic flurbiprofen were administered to rats to create differing extents of competition for protein binding sites between the enantiomers. There was a statistically significant dose-dependent increase in total body clearance and volume of distribution of both the R and S enantiomers. However, there was no change in either the S/R AUC ratio or the elimination rate constants for (R)- or (S)-flurbiprofen with increasing dose. These results are consistent with the hypothesis that the increasing amount of (R)- and (S)-flurbiprofen in the body causes displacement of flurbiprofen enantiomers from their protein binding sites, resulting in their increased total body clearance and volume of distribution. Further, the data suggest that previously reported extents of R to S enantiomeric inversion for other 2-arylpropionates may not be accurate if the enantiomers exhibit nonlinear kinetics or there is a significant kinetic interaction between the enantiomers. PMID- 7983591 TI - Hydrogen bonding. 32. An analysis of water-octanol and water-alkane partitioning and the delta log P parameter of seiler. AB - A general linear solvation energy equation has been used to analyze published partition coefficients in the systems water-octanol (613 solutes), water hexadecane (370 solutes), water-alkane (200 solutes), and water-cyclohexane (170 solutes). The descriptors used in the equation are R2, an excess molar refraction; phi H2, the solute dipolarity/polarizability; sigma alpha H2 and sigma beta H2, the effective solute hydrogen-bond acidity and basicity; and Vx, the characteristic volume of McGowan. It is shown that the water-octanol partition coefficient is dominated by solute hydrogen-bond basicity, which favors water, and by solute size, which favors octanol, but solute excess molar refraction and dipolarity/polarizability are also significant. For the water alkane partition coefficients, the same factors are at work, together with solute hydrogen-bond acidity as a major influence that favors water. An analysis of 288 delta log P values shows that solute hydrogen-bond acidity is the major factor but that solute hydrogen-bond basicity and, to a lesser extent, solute dipolarity/polarizability and size are also significant factors that influence the delta log P parameter. PMID- 7983590 TI - Preformulation studies with melanotan-II: a potential skin cancer chemopreventive peptide. AB - Melanotan-II (1) is a cyclic heptapeptide analogue of alpha-melanocyte stimulating hormone (alpha-MSH) which tans the skin and is currently being evaluated for the prevention of sunlight-induced skin cancers. The dissociation constants of 1 were determined using potentiometric titration and ultraviolet spectrophotometry. The pKa1 (histidine) and pKa2 (arginine) were estimated to be 6.54 and 11.72, respectively. The apparent partition coefficient (PC) was measured at three pH values using both n-octanol and isooctane as the nonpolar phase. The PC(octanol) and delta log PC at pH 7.35 were 2.82 and 1.05, respectively. These data, together with the observance of a bioavailability of 4.6% in the rat, indicate that 1 may be a suitable candidate for oral delivery. The data presented here are useful in developing an appropriate dosage form for 1. PMID- 7983592 TI - Wound healing after laser injury to skin--the effect of occlusion and vitamin E. AB - The skin of Yorkshire pigs was irradiated with various doses of argon and copper vapor laser and evaluated for effects on healing time of pretreatment with topical or intramuscular vitamin E or the Op-Site wound dressing. Incident irradiance for both lasers was between 3.5 and 4.5 W/cm2 for a 10-14-mm beam diameter with a nearly uniform intensity profile. Minimal erythemic dose for the copper-vapor laser was 35 +/- 2 J/cm2 (10 s exposure) and 22.4 +/- 0.1 J/cm2 (6-s exposure) for the argon laser. Three dose levels were administered: a low dose causing light erythema, an intermediate dose, and a high dose causing dermal stasis. The radiant exposures for low, intermediate, and high doses were 35, 70, and 138 J/cm2 for the copper-vapor laser and 22.4, 55, and 129 J/cm2 for the argon laser. Exposure to argon and copper-vapor lasers generally caused wounds with similar healing times. Healing time was significantly decreased for wounds caused by intermediate exposure of the copper-vapor laser and either pretreated with vitamin E or treated with the wound dressing. Healing times for corresponding argon-laser exposure were significantly decreased with pretreatment of intramuscular vitamin E only or after treatment with the wound dressing. These findings may be valuable in selecting treatment for accidental laser skin injuries in man. PMID- 7983593 TI - Effect of sodium deoxycholate on the dissolution and absorption of copper indomethacin and zinc-indomethacin. AB - The effects of sodium deoxycholate on the dissolution of indomethacin metal complexes were investigated. At pH 7.2, the dissolution of copper-indomethacin was very slow, while the dissolution of zinc-indomethacin was higher but less than that of indomethacin. In the presence of 5 mg of sodium deoxycholate, the dissolution of copper-indomethacin and zinc-indomethacin was significantly enhanced. The absorption of zinc-indomethacin in the rat jejunum was low, but that of copper-indomethacin was high, as compared to indomethacin. The addition of 0.2% sodium deoxycholate significantly enhanced the jejunal absorption of zinc indomethacin in the rat, but did not increase the absorption of copper indomethacin. Results indicated that the in vivo absorption behavior of zinc indomethacin was predictable by in vitro dissolution, but such correlation was not applicable to copper-indomethacin. The absorption of copper-indomethacin was similar to that of indomethacin, in spite of its poor dissolution. PMID- 7983594 TI - Quantitative structure-activity relationships for 1,4-dihydropyridine calcium channel antagonists (nifedipine analogues): a quantum chemical/classical approach. AB - A quantum chemical (AM1) combined with a classical study of structure-activity relationships for 1,4-dihydropyridines (nifedipine analogues) was performed. The biological data were taken from the literature. The quantum chemical parameters tested were energies of HOMO and LUMO, dipole moment (total and partial), hardness, Mulliken electronegativity, frontier orbital indices, and others. Also tested were classical parameters like Hansch hydrophobic constant, tau; Hammett electronic constant for the meta position, sigma m; and the Verloop sterimol parameters, B1 and L. The van der Waals volume was also tested. The pharmacological activities of the para monoderivatives are negatively correlated with the molecular volume, i.e. a steric factor. The meta position of the phenyl ring is affected by steric and electronic parameters, whereas the ortho position seems to be affected by hydrophobic and electronic parameters. PMID- 7983595 TI - Physicochemical characterization of the various solid forms of carbovir, an antiviral nucleoside. AB - Carbovir, which exhibits promising in-vitro activity against HIV, is shown to exist in five forms: I, II, III, IV, and V. Forms I-III and V were characterized by differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), hot stage microscopy (HSM), Karl Fischer titrimetry (KFT), powder X-ray diffraction (PXD), intrinsic dissolution rate (IDR) studies, heat of solution measurements (SC), scanning electron microscopy (SEM), Fourier-transform infrared (FTIR) spectroscopy, and water uptake at various relative humidities (water activities). Form IV could not be characterized fully, as it is stable only over a narrow temperature range (267-275 degrees C) which is immediately followed by melting and decomposition. With increasing temperature in DSC, forms I and V transformed successively to form III (195 degrees C), then to form II (220 degrees C), and then to form IV (275 degrees C). The PXD patterns, FTIR spectroscopy, IDR, and SC showed significant differences between these polymorphs. For each of the forms I, II, and III, there exists a critical value of relative humidity above which absorption of water proceeds steeply, leading to the formation of form V, which is more heavily hydrated than any of the other forms. Forms I and V each showed a two-step weight loss in TGA (24-120 degrees C), suggesting the presence of water molecules with two different binding energies probably corresponding to two different locations in the crystal lattice; HSM confirmed the dehydration.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7983597 TI - First-pass metabolism of omeprazole in rats. AB - To clarify the in vivo first-pass metabolism of omeprazole, the pharmacokinetics were examined after oral, intraduodenal (i.d.), intraportal venous (i.p.v), and intravenous (i.v.) administration at various doses to rats. Extraction ratios in the liver and intestinal tract were determined from the areas under the concentration-time curve (AUC) for i.p.v. and i.v. administration and from those for id and ipv administration, respectively. Assuming that the drug was absorbed from the gastrointestinal tract completely, the hepatic and intestinal extraction ratios were 0.80, 0.63, and 0.59 at doses of 2.5, 5, and 10 mg/kg and 0.70 and 0.73 at doses of 5 and 10 mg/kg, respectively. The bioavailability of orally administered omeprazole was 6.4, 9.6, and 12.6% at the doses of 10, 20, and 40 mg/kg, respectively. There were no differences in the distribution volume of steady state, total clearance, or elimination half-life at any doses. In addition, the AUC value after oral administration (20 mg/kg) in rats acutely intoxicated with CCl4 was 2.4 times larger than that in the control. These findings suggest that omeprazole undergoes a first-pass metabolism in the intestinal mucosa and/or lumen, as well as in the liver, and that the major contribution to the dose-dependent increase in bioavailability is a saturation of the first-pass metabolism in the liver. PMID- 7983596 TI - Cytotoxic evaluation of some 3,5-diarylidene-4-piperidones and various related quaternary ammonium compounds and analogs. AB - A number of 3,5-diarylidene-4-piperidones (1) and some related quaternary ammonium salts (5) as well as closely related analogs were prepared principally as candidate cytotoxic agents in two screens. The first test system used an average of 54 human tumor cell lines from eight neoplastic diseases, namely leukemia, melanoma, colon, non-small-cell lung, small-cell lung, central nervous system, ovarian, and renal cancers. Selective toxicity was demonstrated by some of the compounds, especially toward leukemia. The second screen used L1210 lymphoid leukemia cells. In general, the compounds were less cytotoxic than the reference drug melphalan in both screens. Linear plots were made between the Hammett (sigma), fragment (f), and molar refractivity (MR) constants of the nuclear substituents in series 1 and 5 with the IC50 figures of both the human tumor cell lines and L1210 cells. Evaluation against the human tumor cell lines revealed that increases in the f values were correlated with elevation of cytotoxicity in both series 1 and 5; MR constants were also important in series 5. In the L1210 screen, sigma and MR constants were positively correlated with cytotoxicity. X-ray crystallography was undertaken on 3,5-bis-[[4' (methylthio)phenyl]methylene]-1-methyl-4-piperidone methiodide (5d), which had significant cytotoxicity, and 3,5-bis(4-pyridylmethylene)-1-methyl-4-piperidone methiodide (6), which was virtually inactive in both screens.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7983598 TI - Improved automatic kinetic method for the determination of various corticosteroids. AB - Two reaction-rate methods for the determination of corticosteroids at the micromolar level were developed. The methods are modifications of the widely used Blue Tetrazolium and Porter-Silber reactions which are employed for the automatic kinetic determination of corticosteroids using the continuous-addition-of-reagent (CAR) technique. The CAR technique avoided all technical problems typically associated with these reactions such as long incubation at high temperatures, high blank values, and turbidity. On the basis of its analytical figures of merit, the Blue Tetrazolium method was chosen; it allows corticosteroids to be determined at concentrations from 2.7 x 10(-6) to 1.9 x 10(-4) M at a rate of 25 samples/h (triplicate analyses) with an root mean square deviation of ca. 3%. The proposed method was evaluated in recovery experiments and analyses of commercially available formulations. PMID- 7983599 TI - Solubilization of a tripeptide HIV protease inhibitor using a combination of ionization and complexation with chemically modified cyclodextrins. AB - Kynostatin (KNI-272), an experimental HIV protease inhibitor, is currently undergoing preclinical testing for the treatment of AIDS. This transition state mimetic tripeptide exhibits extremely low aqueous solubility (4 micrograms/mL) making target concentrations (5-50 mg/mL) for parenteral solution formulations difficult to achieve. The presence of an ionizable (5-isoquinolinyloxy)acetyl moiety makes solubilization via pH adjustment possible, but a solubility > 5 mg/mL requires an adjustment in pH below 2.0, which would be physiologically unacceptable. This study examines and compares two approaches for solubilizing kynostatin: (1) inclusion complex formation at chemically distinct hydrophobic binding sites using (2-hydroxypropyl)-beta-cyclodextrin (HPCD) and a sulfobutyl ether derivative of beta-cyclodextrin (beta-CD-SBE) and (2) a combined strategy utilizing ionization of the isoquinoline moiety coupled with inclusion complex formation at the remaining binding site(s). Macroscopic binding constants determined from solubility profiles as a function of pH and HPCD concentration have been compared with the microscopic binding constant for formation of the isoquinoline-HPCD inclusion complex determined by UV difference spectroscopy to examine the independence of binding domains within KNI-272. As demonstrated in this report, combination strategies tailored to the properties of different domains within the molecule may be highly effective in solubilizing compounds such as poorly soluble peptides. PMID- 7983600 TI - A rapid HPLC method for the quantification of tyrothricin, menthol, and benzocaine in pharmaceutical formulations. AB - A rapid, sensitive, and accurate reversed-phase HPLC method has been developed for the analysis and quantification of pharmaceutical formulations containing tyrothricin (1), an antibiotic used in antiseptic buccal compressed tablets for local application. The assay has been carried out under isocratic conditions, using a stationary phase of alumina particles coated with polybutadiene and an alkaline mobile phase (pH = 8.2). No HPLC method was reported for the analysis of 1. So, this new technique is an alternative to the slow and tedious microbiological methods. On the other hand, it allows the simultaneous quantification of 1, benzocaine (2), and menthol (3), an aromatic compound not currently analyzed by liquid chromatography. PMID- 7983601 TI - General treatment of competitive binding as applied to the potentiometric ion probe technique: application to the interaction of nonsteroidal anti-inflammatory drugs with bovine serum albumin. AB - The binding of naproxen, ketoprofen, phenylbutazone, salicylic acid, azapropazone, and indobufen to bovine serum albumin was studied by applying the potentiometric ion probe technique. An ion-selective electrode for the ion probe 1-anilino-8-naphthalene-sulfonate was utilized for the purposes of this study. A modified site-oriented competitive binding model was used for the estimation of the drugs' binding parameters, considering different number of binding sites on the competing binding class(es) for the probe and the drug. Calculations were based exclusively on the concentration data of the free probe. The model's ability for accurate estimations of binding parameters was evaluated by simulation studies. The following values of binding parameters were found at 25 degrees C for the drugs under study; naproxen, n1 = 9.1, k1 = 9.4 x 10(5) M-1; ketoprofen, n1 = 8.8, k1 = 10.8 x 10(5) M-1; phenylbutazone, n1 = 3.2, k1 = 1.4 x 10(5) M-1; salicylic acid, n1 = 2.6, k1 = 1.8 x 10(5) M-1, n2 = 21.5, k2 = 1.0 x 10(4) M-1; azapropazone, n1 = 0.5, k1 = 7.8 x 10(5) M-1, n2 = 26.3, k2 = 1.9 x 10(4) M-1; indobufen, n1 = 5.8, k1 = 5.8 x 10(5) M-1, n2 = 19.9, k2 = 3.8 x 10(5) M-1, where ni the number of binding sites of the i class and ki the corresponding association constant. PMID- 7983602 TI - Nuclear magnetic resonance studies of anticonvulsant enaminones. AB - 1H nuclear magnetic resonance (NMR) spectra of enaminones were determined and compared to the anticonvulsant activity of the compounds. Although the precise employment of the NMR data to predict anticonvulsant activity of the enaminones could not be established, general inferences were made. The NMR data confirmed that the enaminones existed predominantly in the amino tautomer, and no evidence was found for the imino tautomer. The ketamine form of the enaminones was supported by the observed spin-spin splittings of the NH with the alpha-protons on certain enaminones. The NH of secondary enaminones was very important in conferring anticonvulsant activity to the enaminones. The peak for the NH proton which could be seen between delta (ppm) 4.50 and 9.70 was present in all of the active enaminones. The tertiary enaminones, which were devoid of the NH proton, were uniformly inactive. It appeared that a combination of steric and electronic effects, lipophilicity, and hydrogen bonding were necessary for the anticonvulsant activity of the enaminones. The cyclic enaminones existed in the trans-S-trans fixed conformation, and the NMR data supported our hypothesis that enantioselectivity is retained in synthesizing enaminones from cyclic, diasteriomeric 1,3-diketones. In addition, the AB system and many unique features were observed in some enaminones. The para, meta, and ortho substituted patterns were observed for monosubstituted phenyl protons, and the NMR patterns for di- and trisubstituted phenyl groups were elucidated. PMID- 7983603 TI - Comparative pharmacokinetics of morning and evening doses of once-a-day theophylline capsules. AB - The objective of this study was to determine if the theophylline diurnal variation that has been observed primarily between morning and evening doses of twice-a-day products could be overcome by a once-a-day formulation. Eighteen healthy, nonsmoking, adult male subjects were given 900-mg theophylline doses as three 300-mg once-a-day theophylline capsules in the morning or evening for 5 days in a single-blind fashion. Matching placebo capsules were administered midway between each dose of active drug. Predose theophylline serum levels on day 3-6 were statistically equivalent within each treatment, indicating that approximate steady-state conditions were achieved by day 3. Mean serum level profiles over the 24-h interval following the active dose on day 5 were almost superimposable for the morning and evening treatments. All pharmacokinetic parameters were equivalent between the treatments, except for the time to peak serum level (Tmax), which was significantly shorter for the morning dose. Given the flatness of the serum level curves for both treatments, the Tmax difference was judged to be clinically unimportant. A small peak-trough level fluctuation of about 50% was seen with each treatment. We conclude that by designing a dose form in which drug release was the rate-limiting step in drug absorption, the diurnal variation commonly associated with theophylline formulations may be eliminated. PMID- 7983604 TI - FT-IR and near-infrared FT-Raman studies of the secondary structure of insulinotropin in the solid state: alpha-helix to beta-sheet conversion induced by phenol and/or by high shear force. AB - Insulinotropin (glucagon-like peptide I) is a peptide containing 31 amino acid residues. It stimulates the secretion of the hormone insulin. The solubility of this peptide is highly dependent on its environment and the treatment that it has undergone. For instance, synthetic insulinotropin is highly soluble in neutral phosphate-buffered saline (1 mg/mL). However, the application of shear force by stirring renders it extremely insoluble (1 micrograms/mL). This property may be explained in terms of a change in peptide secondary structure with no alteration in primary structure. In order to understand this phenomenon, FT-IR and near-IR FT-Raman were employed to examine four samples prepared under different experimental conditions. It was found that solubility decreases as the alpha helix is converted to an antiparallel beta-sheet structure. PMID- 7983606 TI - Influence of sex on the stereoselective probenecid-ketoprofen interaction in the rat. PMID- 7983607 TI - An in-depth analysis of pharmaceutical cocaine: cocaethylene and other impurities. PMID- 7983605 TI - Metabolic kinetics of nonproductive binding inhibition. PMID- 7983608 TI - Plasma protein binding of highly bound drugs: implications of radiochemical impurities. PMID- 7983609 TI - Rethinking traditional weight management programs: a 3-year follow-up evaluation of a new approach. AB - We evaluated the effectiveness of a nondiet approach designed to reduce restrained eating behaviors and improve self-acceptance and self-esteem. This approach also encourages participants to address eating and exercise behavior separately. Subjects were Conoco employees who participated in the Wellness Department's Eat For L.I.F.E. (Long-term change; Image of self; Fun; Enjoyment of eating) program and completed pre-participation and 3-year follow-up questionnaires (N = 79). Pre- and postsurvey data were used to assess participants eating behavior, dieting behavior, self-acceptance, self-esteem, level of physical activity, and demographic information. Mastery of the internally directed eating style was assessed during the program at 3 months, at the conclusion of the 6-month program, and at the 3-year follow-up. Analysis of variance indicated that Eat For L.I.F.E. participants were able to significantly decrease their restrained eating behavior and increase self-acceptance, self esteem, and level of physical activity. Participants also were able to adopt many aspects of the nonrestrained, internally directed eating style and decrease their frequency of weighing-in behavior. These results indicate that strategies fostering internally directed eating behaviors may be more centrally related to an individual's well-being than programs supporting externally directed eating behaviors. PMID- 7983612 TI - The effects of stereotyping on impression formation: cross-cultural perspectives on viewing religious persons. AB - We examined the effects of stereotyping on impression formation when encountering people dressed to represent a religious faith. We used stimulus photographs of eight male and female models dressed casually and a second photograph of one male and one female model in religious attire that was placed beside the control photos of models dressed causally. From each set of photographs, subjects selected a photo of the person with whom they would associate the various positive personality traits suggested by our stimulus questions. Subjects were students from a U.S. Catholic school, a U.S. public school, and a Malaysian Muslim school. All the subjects attributed more of the positive traits to photos of the models who were religiously attired than to photos of those who were casually dressed, but subjects from U.S. schools attributed more of the positive traits to the photos of religiously dressed models than did the subjects from the Malaysian school. PMID- 7983611 TI - The relationship of satisfaction with life to personality characteristics. AB - We administered a self-report questionnaire to 1,749 adult Australians between 17 and 40 years old to examine the predictive values of self-esteem, depression, locus of control, trait anger, religiosity, psychological reactance, and age in relation to life satisfaction. Results of independent regression analyses showed that all but psychological reactance were significant predictors of life satisfaction. In the stepwise analysis, self-esteem, depression, trait anger, locus of control, and religiosity were significant, and together accounted for 26.3% of the total variance of life satisfaction. In both the stepwise and independent analyses, self-esteem and depression affected levels of satisfaction more than any other variables. PMID- 7983610 TI - Locus of control of Israeli women during the transition to marriage. AB - Sixty Israeli women were administered Rotter's (1966) Locus of Control Scale and Zung's (1965) Self-Rating Depression Scale 1 to 2 months prior to their marriages. Six to 8 weeks after they were married, they responded to Spanier's (1976) Dyadic Adjustment Scale and again to the Zung scale. There was a low but significant correlation between externality and depression following marriage. Mean depression scores for the total sample, and for women with internal, medium, and external locus of control (LOC) were significantly lower after marriage. Women with external LOC manifested significantly more change in depression scores before and after marriage and also rated themselves significantly less satisfied with their marriages. Depression prior to marriage was predictive of later marital dissatisfaction, and depression following marriage was highly correlated with concurrent dissatisfaction. PMID- 7983613 TI - Perceived control, illness status, stress, and adjustment to cardiac illness. AB - A sample of 71 cardiac patients was assessed using the Multidimensional Health Locus of Control Scales (Wallston, Wallston, & DeVellis, 1978) and a measure of outcome expectancies specific to cardiac recovery. Variables included life stress, chronicity of the heart disease, and the level of symptoms reported. Appraisals of control were unrelated to psychological distress when contextual variables were statistically controlled. An interactive effect between the level of life stress and perception of control was significantly associated with psychological distress. These results provide additional support for the inclusion of contextual variables in research on the effects of control appraisals. PMID- 7983614 TI - Extrinsic occupational needs and the relationship between need for achievement and locus of control. AB - Because of contradictory correlations between occupational need for achievement (nAch) and locus of control (LOC), this study tested the extrinsic need for job security (nSec) as a moderator of the association. A total of 383 female subjects in two occupations were studied. A high level of nSec externalized internal LOC beliefs associated with a high level of nAch. Depending on occupational group, nSec, or its absence, could also be the sole predictor of LOC, thus also causing the positive correlation between nAch and LOC. In subjects over 50 years old, internal LOC was associated with presence of a high level of nSec. The correlational association between nAch and LOC is limited and misleading because of the contribution of nSec to the association between these two variables. PMID- 7983615 TI - Does occupational stereotyping still exist? AB - We surveyed 113 college students regarding their views of certain occupational stereotypes. Our results indicated that in this population gender was related to the subjects' views of occupations as either male, female, or neutral, and that the father's primary occupation significantly affected the subjects' views of only one occupation--clinical sociologist. The mother's occupational seemed to have no effect. PMID- 7983616 TI - Locus of control, machiavellianism, and managerial job performance. AB - In this study, we examined the moderating effect of locus of control on the relationship between Machiavellianism and job performance of store managers in a retail setting. Our results indicated a significant moderating effect for managers who perceive that they have an external control orientation but not for managers with an internal control orientation. PMID- 7983617 TI - A survey of public utilization of self-help materials. PMID- 7983618 TI - The effects of n-3 fatty acid supplementation on bleeding time, plasma fatty acid composition, and in vitro platelet aggregation in cats. AB - Dietary supplementation with fish and fish oils rich in the n-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) has been shown to alter eicosanoid metabolism and impair platelet function in several species. As an initial step in evaluating the antithrombotic effect of these n-3 fatty acids in cats, purified EPA and DHA were administered daily to 8 clinically normal cats for 2 months. Platelet function was evaluated biweekly by determining mucosal bleeding time and in vitro platelet aggregation parameters. Plasma fatty acid profiles were obtained before fish oil supplementation and at the termination of the study. In spite of significant increases (P < .0001) in the plasma concentrations of EPA and DHA after n-3 fatty acid supplementation, there were no significant changes in platelet aggregation or bleeding times. Although it is tempting, based on extrapolation of data from other species, to recommend dietary supplementation with fish oil for cats prone to arterial thromboembolism, these results indicate that administration of large doses of purified EPA and DHA once daily does not inhibit platelet function in normal cats and is unlikely to prevent thrombosis in cats with cardiovascular disease. Additional studies are recommended to ascertain whether more frequent administration of these purified n 3 fatty acids or continual feeding of diets high in n-3 fatty acid content will impair platelet function. PMID- 7983619 TI - Evaluation of an additive solution for preservation of canine red blood cells. AB - The effect of an additive preservative solution on canine red blood cell posttransfusion viability (PTV) and on selected canine red blood cell biochemical parameters was studied. One unit (450 mL) of blood was collected from 6 clinically normal dogs into the anticoagulant citrate phosphate dextrose, centrifuged, and the plasma removed. The red blood cells were then suspended in 100 mL of a saline, adenine, dextrose, and mannitol solution and stored at 4 degrees C. Aliquots were removed for study at 1, 10, 20, 30, 37, and 44 days. The 24-hour PTV of autologous red blood cells was determined using a sodium chromate (51Cr) label. Red blood cell concentrations of 2,3-diphosphoglycerate (2,3-DPG), adenosine-5'-triphosphate (ATP), and pH were also determined. Canine red blood cell PTV, pH, ATP, and 2,3-DPG concentrations decreased during storage (P < .05). The PTV decreased from 94% using day 1 red blood cells to 80% and 75% using day 37 and day 44 red blood cells, respectively (P < .05). Although the mean PTV of the day 44 stored units equaled the Food and Drug Administration (FDA) minimum standard for human red blood cells, the PTV was substandard in 75% of the day 44 units. The FDA standard was exceeded in 83% of the day 37 units. It was concluded that 37-day-old canine red blood cells preserved with a saline, adenine, dextrose, and mannitol solution are of acceptable quality for transfusion. PMID- 7983620 TI - Intravascular leukostasis and systemic aspergillosis in a horse with subleukemic acute myelomonocytic leukemia. AB - Leukemia is a neoplastic disease of one or more of the cell types of the hemopoietic system and is rarely diagnosed in the horse. This report describes a case of subleukemic acute myelomonocytic leukemia in an 11-year-old gelding. Preliminary cytological diagnosis was supported by two types of laboratory investigations. Cytochemical characterization of blood and bone marrow neoplastic cells was consistent with a myelomonocytic origin. Neoplastic blast cells in peripheral blood were labeled by monoclonal antibodies specific for cell surface molecules of horse granulocytes, but they were not labeled by antibodies to T- or B-lymphocytes or macrophages. Treatment was attempted but was unsuccessful. At necropsy, intravascular leukostasis was present in all tissues examined. Fungal hyphae were also found in lung interstitium and colonic submucosa, suggesting the presence of a systemic mycosis. Nucleated cells were isolated from peripheral blood and cultured in vitro; they survived for up to 2 weeks and had evidence of cell division that was not sustained. Frozen-thawed cells stored in liquid nitrogen were also successfully cultured in vitro, but no permanent cell lines could be established. PMID- 7983621 TI - A retrospective study of vein thrombosis in horses treated with intravenous fluids in a veterinary teaching hospital. AB - The medical records of 68 horses treated with IV fluids for 24 hours or more were reviewed to determine the risk of vein thrombosis and to determine which factors were associated with the occurrence of vein thrombosis in these horses. Three factors were positively associated with vein thrombosis including use of locally produced fluids and presence of fever and diarrhea. Two factors, having general anesthesia or having surgery, were negatively associated with vein thrombosis. One continuous variable, duration of treatment, was positively associated with vein thrombosis. Factors not associated with vein thrombosis included breed, age, sex, type of catheter, outcome (lived or died), laminitis, colic, other drugs via the catheter, and type of surgery. One type of catheter was used in the majority of horses (57) making it difficult to detect effect of catheter type. Preparation of the catheter site, the person placing the catheter, and technique of catheter maintenance were not evaluated. Like all retrospective studies, this study has limitations to the conclusions that can be made; however, the strong association between source of fluids, fever, diarrhea, anesthesia/surgery, and the occurrence of vein thrombosis merits consideration in the clinician's therapeutic plan. PMID- 7983622 TI - 0-7-21 radiation therapy for the treatment of canine oral melanoma. AB - Eighteen dogs with malignant melanoma of the oral cavity were treated with high dose per fraction (0-7-21) radiation therapy. Eight hundred cGy was administered on days 0, 7, and 21 for a total dose of 2,400 cGy in 3 weeks. Of 17 dogs evaluated, 9 (53%) had a complete remission and 5 (30%) achieved a partial remission with an overall response rate of 83%. Local failure occurred in 2 of the 9 dogs where a complete response was initially observed. One dog died of intercurrent disease, and one died of metastatic disease without evidence of local recurrence. Five dogs are alive and free of disease 9 to nineteen months from the initiation of therapy. The 0-7-21 protocol was well-tolerated, and acute radiation reactions were low-grade and limited to the skin. The results of this study demonstrate that oral melanomas in dogs are responsive to radiation. 0-7-21 radiation therapy offers a viable alternative to radical excision, especially when tumor volume or location would require cosmetically or functionally debilitating surgery. PMID- 7983623 TI - Piroxicam therapy in 34 dogs with transitional cell carcinoma of the urinary bladder. AB - Thirty-four dogs with histopathologically confirmed, measurable, nonresectable transitional cell carcinoma of the urinary bladder were treated with piroxicam (0.3 mg/kg PO sid) and were evaluated for tumor response and drug toxicity. Dogs were evaluated at the Purdue University Veterinary Teaching Hospital by means of physical examination, thoracic and abdominal radiography, cystography, complete blood count, serum biochemistry profile, and urinalysis. In selected cases, prostaglandin E2 (PGE2) concentrations in plasma and in supernatants of stimulated monocytes, and natural killer cell activity were quantified. Dogs were evaluated before therapy and at 28 and 56 days after initiation of therapy. Dogs with stable disease or remission at 56 days remained on the study and were evaluated at 1 to 2 months intervals. Tumor responses were 2 complete remissions, 4 partial remissions, 18 stable diseases, and 10 progressive diseases. The median survival of all dogs was 181 days (range, 28 to 720+ days), with 2 dogs still alive. Piroxicam toxicity consisted of gastrointestinal irritation in 6 dogs and renal papillary necrosis (detected at necropsy) in 2 dogs. Monocyte production of PGE2 appeared to decrease with therapy in dogs whose tumors were decreasing in size, and increased in dogs with tumor progression. A consistent pattern in natural killer cell activity was not observed. In vitro cytotoxicity assays against 4 canine tumor cell lines revealed no direct antitumor effects of piroxicam. In summary, antitumor activity, which was not likely the result of a direct cytotoxic effect, was observed in dogs with transitional cell carcinoma of the bladder treated with piroxicam. PMID- 7983624 TI - Use of the thyrotropin releasing hormone stimulation test to diagnose mild hyperthyroidism in cats. AB - We evaluated serum T4 and T3 concentrations before and after administration of thyrotropin releasing hormone (TRH) in 35 cats with mild to moderate hyperthyroidism, 15 cats with nonthyroidal disease, and 31 clinically normal cats. The TRH stimulation test was performed by collecting blood for serum T4 and T3 determinations before and 4 hours after IV administration of 0.1 mg/kg TRH. Mean basal serum thyroid hormone concentrations in hyperthyroid cats were significantly (P < .05) higher than concentrations in normal cats and in those with nonthyroidal disease, but there was considerable overlap among the 3 groups. After administration of TRH, mean serum T4 concentrations increased significantly in all groups of cats, whereas mean T3 concentrations increased significantly in normal cats and in those with nonthyroidal disease, but not in cats with hyperthyroidism. The absolute difference between mean basal and TRH-stimulated serum concentrations of T4 in cats with hyperthyroidism (10.7 nmol/L) was significantly lower than the difference in the cats with nonthyroidal disease (20.0 nmol/L) and in clinically normal cats (28.3 nmol/L), but there was considerable overlap in values among groups. The mean value for relative change in serum T4 concentration after TRH was significantly lower in cats with hyperthyroidism (18.9%) than in those with nonthyroidal disease (110.0%) and in clinically normal cats (130.2%). Serum T4 concentrations increased by > 50% in all normal cats and cats with nonthyroidal disease, whereas only 4 (11.4%) of the 35 hyperthyroid cats had an increase of > 50% after TRH administration.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7983625 TI - Basal and ACTH-stimulated plasma aldosterone concentrations are normal or increased in dogs with trichuriasis-associated pseudohypoadrenocorticism. AB - We measured plasma concentrations of cortisol and aldosterone before and after administration of adrenocorticotropin (ACTH) in dogs with trichuriasis. These dogs had physical examination, historical, and serum electrolyte findings suggestive of hypoadrenocorticism; trichuriasis-associated pseudohypoadrenocorticism has been reported previously. We found normal basal and ACTH-stimulated plasma cortisol concentrations. Basal and ACTH-stimulated plasma aldosterone concentrations were normal in 2 dogs and increased in 3 dogs, suggesting that the electrolyte abnormalities seen in this clinical syndrome are not due to aldosterone deficiency. PMID- 7983627 TI - Brain stem auditory-evoked response abnormalities in 14 dogs with confirmed central nervous system lesions. AB - Abnormal brain stem auditory-evoked responses (BAER) were recorded on 14 dogs with brain lesions confirmed by necropsy (n = 13) or magnetic resonance imaging and surgical biopsy (n = 1). Lesions included brain stem or cerebellar tumors (6 dogs), brain stem trauma (1 dog), forebrain tumors (3 dogs), hydrocephalus (2 dogs), granulomatous meningoencephalitis (1 dog), and meningoencephalitis (1 dog). Five affected dogs were comatose at the time of recording. BAER abnormalities could be classified as (1) absence of some or all of waves I to V, (2) increased latencies, with wave V being most frequently affected, or (3) a reduction in the amplitude ratio of waves V/I. PMID- 7983626 TI - A tremor syndrome with a central axonopathy in Scottish terriers. AB - A central axonopathy in 2 male and 1 female Scottish Terrier puppies from 3 different but related litters is reported. Clinical signs consisting of severe whole-body tremors and ataxia were first detected at the age of 10 to 12 weeks. They worsened with activity and excitement and diminished during rest or sleep. Two dogs also had paraparesis. In 1 dog the neurological deficits progressed over several months. Neuropathological examination revealed widespread axonal changes, vacuolation, and gliosis in the white matter of the central nervous system. PMID- 7983628 TI - Cytosine arabinoside as a single agent for the induction of remission in canine lymphoma. AB - Cytosine arabinoside (AraC) was administered as a continuous IV infusion to 15 dogs with malignant lymphoma at a dose of 300 mg/m2/d for 2 consecutive days. Dogs were re-examined 7 d after treatment for response to therapy and for hematologic toxicity. Regardless of response, all dogs were started on combination chemotherapy at this time. Other toxicities were reported by owners. No dog responded objectively to Ara-C treatment, although 1 dog with circulating lymphoblasts had partial regression of lymphadenopathy but persistent blastemia. Thrombocytopenia (platelet count < 200,000/microL) 7 days posttreatment was the most commonly encountered hematologic toxicity, occurring in 10 of 14 dogs. Three of these 10 dogs were also mildly neutropenic (neutrophil counts of 2000 to 3000 cell/microL). Nonhematologic toxicity occurred in 8 of 15 dogs and was principally gastrointestinal in nature and mild in severity. Cytosine arabinoside at a dose of 300 mg/m2/day was not considered an active drug for the induction of remission in dogs with lymphoma. PMID- 7983629 TI - Quantitative aspects of thyroid scintigraphy with pertechnetate (99mTcO4-) in cats. AB - Thyroidal 99mTcO4- (pertechnetate) uptake percentages were determined in unanesthetized euthyroid (n = 13) and hyperthyroid (n = 18) cats. Maximal uptakes were observed 60 minutes after IV injection of the radionuclide and ranged from 0.3 to 3.9% of the dose in euthyroid cats (median 2.23%) and from 5.2% to 23.9% of the dose in hyperthyroid cats (median 14.8%) (P < .05). There were no overlaps in pertechnetate uptake percentages during any of the intervals evaluated. It is concluded that the optimal time for visualization of the thyroid by 99mTcO4(-) scanning is 60 minutes after IV injection of the radionuclide. Calculation of the percentage uptake is of additional diagnostic value. PMID- 7983630 TI - Successful treatment of guttural pouch mycosis with itraconazole and topical enilconazole in a horse. PMID- 7983631 TI - Right ventricular cardiomyopathy in a dog. PMID- 7983632 TI - Mitral stenosis in dogs. PMID- 7983633 TI - Rheumatic diseases in China. PMID- 7983634 TI - How many types of patients meet classification criteria for rheumatoid arthritis? PMID- 7983635 TI - Evaluating biologic agents in rheumatoid arthritis: a framework for clinical trials. PMID- 7983636 TI - Osteoarthritis and bone mass. PMID- 7983637 TI - Seronegative and weakly seropositive rheumatoid arthritis differ from clearly seropositive rheumatoid arthritis in HLA class II associations. AB - OBJECTIVE: To study the role of HLA class II genes in conferring susceptibility to seronegative vs seropositive rheumatoid arthritis (RA). METHODS: The distribution of DRB1 and DPB1 alleles in 33 seronegative, 20 weakly seropositive, 79 distinctly seropositive patients with RA, and in 181 healthy controls was determined by genomic typing: IgM rheumatoid factor (RF) seronegativity was ascertained in Waalers' latex, and ELISA tests. RESULTS: DRB1*0101/2 (encoding variants of DR1) was associated with weakly seropositive RA (and possibly seronegative RA) but not the clearly seropositive disease. In contrast DRB1*0401 and DRB1*0408 (encoding the Dw4 and Dw14.2 variants of DR4, respectively) were associated with clearly seropositive RA but were not increased among patients having weakly seropositive or seronegative RA. DRB1*0404 (encoding the Dw14.1 variant of DR4) was increased to some extent in all examined RA subsets. The distribution of DPB1 alleles in the patients was as in the controls. CONCLUSION: Seronegative and weakly seropositive RA differ from clearly seropositive RA in HLA class II associations. PMID- 7983638 TI - Proliferative response of synovial fluid mononuclear cells of patients with rheumatoid arthritis to mycobacterial 65 kDa heat shock protein and its association with HLA-DR+.gamma delta+ T cells. AB - OBJECTIVE: The proliferative response of mononuclear cells (MNC) in synovial fluid (SF) and peripheral blood (PB) of patients with rheumatoid arthritis (RA) to mycobacterial 65 kDa heat shock protein (HSP65) was tested and the response compared with the percentage of HLA-DR+.gamma delta+ T cells in lymphocytes of SFMNC or PBMNC: METHODS: Proliferative response of MNC was measured by means of 3H-thymidine incorporation and expressed by means of the stimulation index. Percentage of HLA-DR+.gamma delta+ T cells in lymphocytes was measured by means of the 2-color flow cytometry method. RESULTS: Higher response of SFMNC than PBMNC to HSP65 was noted in 14 of 19 patients with RA. Stimulation indexes of RA SFMNC correlated significantly with HLA-DR+.gamma delta+ T cell percentage in lymphocytes. CONCLUSION: In the SF of patients with RA, an accumulation of HSP65 reactive and HLA-DR+.gamma delta+ T cells was noted. PMID- 7983640 TI - A comparison of the performance of different methods of disease classification for rheumatoid arthritis. Results of an analysis from a nationwide twin study. AB - OBJECTIVE: We have assessed the importance of the distinction between classification criteria for rheumatoid arthritis (RA) that recognize the presence of currently active disease from those that, in addition, incorporate evidence of past disease activity in ascertaining disease occurrence. We applied 7 classification schemes to a population of twins with inflammatory arthritis to determine (a) the number of individuals classified as RA positive by each scheme and hence the effect on the estimate of disease concordance in the twins and (b) their performance in correctly assigning a diagnosis compared with a physician's opinion. METHODS: The schemes assessed were the 1958 ARA (Rome) criteria which detect active disease, the 1966 New York (using both the 2/4 and 3/4 published cutoffs) which detect "ever" disease and 4 variants of the 1987 ARA criteria. These were the 4/7 and decision tree approaches applied on the basis of the relevant features (1) being present at the time of the study and (2) being present ever and allowing current joint deformity to substitute for absent joint swelling. RESULTS: In all, 283 individuals with a history of joint swelling were assessed, 255 of whom were considered to have RA by their physician. Criteria used to recognize "current" RA identified only about 70% of those which recognized RA ever. These differences in ascertainment level produced a marked effect on the monozygotic twin RA concordance estimates with percentages ranging from 10 to 18%. The results from receiver operating curves confirmed that criteria used to assess only current RA were too insensitive to be of value. Of the criteria that recognized RA status ever the 1987 ARA performed best overall. CONCLUSION: The use of classification methods that incorporate past as well as current evidence of disease activity is essential to avoid important misclassification in epidemiological and family studies. The 1987 criteria, applied retrospectively and allowing joint deformity to substitute for swelling, are of enhanced value over other existing schemes. PMID- 7983639 TI - Synovial fibroblast-like cell transfection with the SV40 large T antigen induces a transformed phenotype and permits transient tumor formation in immunodeficient mice. AB - OBJECTIVE: To understand the intracellular signals leading to transformed-like growth of synovial fibroblast-like cells from patients with rheumatoid arthritis (RA). METHODS: Cell lines stably transfected with one or both of 2 complementary oncogenes, the SV40 large T antigen and the ras oncogene, were studied for phenotypic changes. RESULTS: Synovial fibroblast-like cells stably transfected with the SV40 large T antigen, but not the ras oncogene, showed high levels of growth factor independent proliferation, grew under anchorage independent conditions, expressed cathepsin L mRNA, and formed transient tumors in immunodeficient mice. Synovial fibroblast-like cells stably transfected with both oncogenes appeared phenotypically similar to synovial fibroblast-like cells transfected with the large T antigen alone. CONCLUSION: The SV40 large T antigen confers a phenotype on synovial fibroblast-like cells similar to that stimulated by growth factors, suggesting that it stimulates the same intracellular signalling pathway leading to cytokine induced, transformed synovial fibroblast like cell growth. When injected into immunodeficient mice these transfected cells formed tumors characterized by rapid, transient growth, central necrosis, and neutrophil infiltration. PMID- 7983641 TI - Decreased testosterone levels in men with rheumatoid arthritis: effect of low dose prednisone therapy. AB - OBJECTIVE: To determine whether men with rheumatoid arthritis (RA) have abnormal hypothalamic-pituitary-gonadal axis function and to measure the effects of low dose prednisone therapy in these patients. METHODS: We measured testosterone, follicle stimulating hormone (FSH), and luteinizing hormone (LH) in 36 men aged 38-75 (mean age +/- 1 sd = 62 +/- 10 years) who had longstanding active RA (mean disease duration = 17 +/- 12 years) and in 70 healthy elderly male controls, aged 53-83 (mean age 68 = +/- 6 years). We divided the group with RA into those taking no prednisone (n = 12) and those taking 5 to 10 mg/day of prednisone (n = 24) and analyzed these groups separately to determine whether low doses of prednisone affected testosterone levels. RESULTS: Compared to the healthy controls, patients with RA not taking prednisone had normal testosterone levels but significantly elevated levels of FSH and LH (p < 0.01 for both comparisons). In contrast, patients with RA taking prednisone had significantly lower testosterone levels (p < 0.05), but levels of FSH and LH were only slightly elevated compared to controls. Compared to patients not taking prednisone, patients taking prednisone had lower levels of testosterone, FSH, and LH. CONCLUSION: Male patients with RA who are not taking prednisone have significantly elevated levels of FSH and LH with normal testosterone levels, suggesting a state of compensated partial gonadal failure. Male patients with RA taking low doses of prednisone have lower testosterone and gonadotropin levels, suggesting that prednisone may suppress the hypothalmic-pituitary-testicular axis. Since testosterone affects immune function as well as bone and muscle metabolism, androgen deficiency in some men with RA may predispose these patients to more severe disease and to increased complications of steroid therapy such as myopathy and osteoporosis. PMID- 7983642 TI - More evidence from a community based series of better outcome in rheumatoid arthritis. Data on the effect of multidisciplinary care on the retention of functional ability. AB - OBJECTIVE: To examine the severity of rheumatoid arthritis (RA), as defined by the American Rheumatism Association (ARA) 1987 revised criteria, at the population level. METHODS: The level of functional disability of the 103 patients with RA who represented practically all subjects with RA in a rural community of 13,000 adult inhabitants was assessed by the ARA Functional Classification and the Health Assessment Questionnaire (HAQ). RESULTS: Only one of the 103 patients was bedridden (ARA Class IV). According to the HAQ Functional Disability Index (FDI) two thirds of the patients had mild or at most moderate disability. Overall, less than 10% of the patients in the community were severely disabled. CONCLUSION: The level of disability in our series is lower than that reported earlier in populations with RA. These patients were treated aggressively with a median interval of one year from the first joint symptoms to the start of disease modifying antirheumatic drugs and had a median number of 2 orthopedic operations. How these interventions influenced the result cannot be accurately assessed on the basis of our cross sectional study protocol. However, high grade impairment due to destruction of large joints of lower limbs was in most instances compensated by total joint replacement surgery, performed in 20% of the cases in the series. This may partly explain the low prevalence of totally disabled patients with severe restriction in mobility in this population. PMID- 7983643 TI - Outcome in rheumatoid arthritis. A 1985 inception cohort study. AB - OBJECTIVE: Our purpose was to describe the clinical status and outcome of a 1985 inception cohort of patients with rheumatoid arthritis (RA), retrospectively established. METHODS: All patients with RA in Edmonton, with a possible onset of disease in 1985, and who consulted a rheumatologist at any time from January, 1985 through June, 1991 were considered for inclusion in the cohort. Patients were contacted and assessed between August, 1991 and June, 1992. The following indices were used as outcome measures: joint counts, radiological scores of hand radiographs and the modified Health Assessment Questionnaire for activities of daily living (MHAQ). RESULTS: One hundred and twenty eight patients were included in the cohort (70% were women; age at onset was 52 +/- 13 years). At the time of the assessment, 41 patients (32%) had no articular swelling. Twenty-nine patients (23%) had a radiological score of 0, and 39 (31%) had no erosions. The mean MHAQ score was 0.49 +/- 0.47; 39 patients (31%) had a score of 0 (normal function). Rheumatoid factors and nodules were related to more severe outcomes. Sex, age at onset and mode of onset were not related to prognosis. Most patients had received 2nd line therapy within the first 3 years of RA. CONCLUSION: Our results suggest that the prognosis of RA after 6-7 years of disease is not as ominous as has been suggested by others. Since most of the previous studies have been conducted in prevalent cases attending tertiary centers, a selection bias may be responsible for some of these results. Since these patients were treated early in the course of the disease, the beneficial effects of prompt 2nd line therapy cannot be excluded. PMID- 7983644 TI - Synovial lymphocytes indicate "bacterial" agents may cause some cases of rheumatoid arthritis. AB - OBJECTIVE: To evaluate synovial lymphocyte response data from "rheumatoid" patients, to determine if "bacterial" antigens caused significant stimulation. METHODS: Two-tailed t tests, analysis of variance, and metaanalysis were applied to 3H-thymidine uptake triplicate/quadruplicate counts, resulting from microbiological antigen stimulation of synovial fluid lymphocytes. RESULTS: In 5 patients with rheumatoid arthritis, maximal synovial lymphocyte responses to chlamydial (in 3) and salmonella (in 2) antigens were significantly greater than to other tested antigens. CONCLUSION: The data, associated with other published data from similar studies, suggest that Chlamydia and pathogenic Enterobacteriaceae may be etiologically related to the arthritis of some patients with rheumatoid arthritis. PMID- 7983645 TI - Heterogeneity of the anti-Ro(SSA) response in rheumatic diseases. AB - OBJECTIVE: The immune response to the Ro(SSA) antigen is heterogeneous. Anti Ro(SSA) positive sera may contain antibodies recognizing either a 60 or a 52 kDa polypeptide component of the Ro(SSA) particle. Thus we sought to determine the profile of anti-Ro(SSA) antibodies defined by immunoblotting in patients with rheumatic diseases. METHODS: Immunoblotting against human placenta extract and ELISA against recombinant Ro(SSA) antigen as confirmatory tests were done to detect anti-Ro(SSA) antibodies in 563 sera from patients with systemic lupus erythematosus (SLE). Sjogren's syndrome (SS), rheumatoid arthritis (RA) and other connective tissue diseases. RESULTS: Anti-52 kDa antibodies were more common in primary patients with SS (9/22; 40.9%) than in patients with SLE (29/135; 21.4%) or patients with RA (7/315; 2.2%). Anti-60 kDa antibodies were more frequent in patients with SLE (26/135; 19.2%) than in patients with primary SS (2/22; 9%) or RA (17/315; 5.3%). None of the 22 patients with primary SS had only antibodies to the 60 kDa polypeptide. Among the 153 patients whose sera were positive by ELISA, 73 (47.7%) were negative by immunoblotting. The most frequent diagnoses in these sera were RA and SLE. The anti-52 kDa sera had higher optical density values compared to anti-60 kDa sera. CONCLUSIONS: Our observations indicate the existence of qualitatively and quantitatively different anti-Ro(SSA) responses in the rheumatic diseases. The major responses are anti-52 kDa antibodies in primary SS, both anti-52 and anti-60 kDa antibodies in SLE, and anti-60 kDa antibodies in RA and other connective tissue diseases. PMID- 7983646 TI - Comparison of hydroxychloroquine and placebo in the treatment of the arthropathy of mild systemic lupus erythematosus. AB - OBJECTIVE: To compare the relative safety and efficacy of hydroxychloroquine (HCQ) and placebo (Pl) in the treatment of the articular complaints of systemic lupus erythematosus (SLE). METHODS: Seventy-one patients with mild SLE requiring < or = 10 mg of prednisone or equivalent daily and with arthritis or arthralgias were entered into a 48-week prospective, controlled, double blind multicenter trial and randomly assigned to either HCQ or Pl. RESULTS: Both HCQ and Pl were well tolerated in the 48-week trial. There were no remissions. With the exception of the patient assessment of joint pain, all other joint measures were similar between the groups. Twenty-nine patients withdrew before the end of the trial although only 2 patients withdrew for adverse drug effects. CONCLUSION: Our study found subjective pain relief as the only statistically significant difference in joint count variables from HCQ in the treatment of the articular manifestations of SLE. PMID- 7983647 TI - Late onset lupus: a clinical and immunological study in a predominantly Chinese population. AB - OBJECTIVE: To compare retrospectively the clinical, laboratory, and immunological features between 50 patients with early and 26 with late onset (> 50 years old) systemic lupus erythematosus (SLE) and to observe differences between our predominantly Chinese and Caucasian patients with late onset SLE. METHODS: Case records of 76 consecutive patients (age: 10-73 years) who attended the rheumatology clinic during the study period were reviewed. Chinese constituted 89.4% of the study population. RESULTS: Compared to the early onset patients, the late onset lupus patients tended to have an insidious onset of disease, lower female predominance and less frequent complaints of fever, alopecia, arthritis, and malar rash at presentation (p < 0.05). Peripheral neuropathy, myalgias, pancytopenia, and elevated liver enzymes were more commonly found in the late onset than in the early onset lupus during followup. Major organ involvement was relatively uncommon in late onset patients. No sex related differences could be demonstrated with respect to the mean age of onset of disease and clinical manifestations. No significant serological differences were detected between the 2 groups. The cause of death in the late onset group was often treatment related. CONCLUSION: Differences in disease manifestations were found between the early and late onset lupus patients. The disease expression in our predominantly Chinese elderly patients with lupus also differs from the Caucasian patients. However, the insidious onset and milder disease in the late onset group is in agreement with other studies. PMID- 7983648 TI - Sensitivity to change of 3 Systemic Lupus Erythematosus Disease Activity Indices: international validation. AB - OBJECTIVE: Three indices, the SLE Disease Activity Index (SLEDAI), the Systemic Lupus Activity Measure (SLAM) and the British Isles Lupus Assessment Group (BILAG), have been found to be reliable and valid measures of disease activity in patients with systemic lupus erythematosus (SLE). Our aim was to investigate their use and comparative ability to assess change in disease activity over time. METHODS: Clinical and laboratory features of 8 patients with SLE on each of 3 consecutive visits were abstracted and sent in 3 separate packages to physicians from 8 centers. The order of the patient visit summaries was randomized, and the 3 indices rated in one of 6 specific sequences. RESULTS: The 3 indices were significantly (p < 0.01) correlated: SLEDAI/SLAM = 0.61, BILAG/SLAM = 0.55, SLEDAI/BILAG = 0.35. The sequence presented, the order of patients and order of index scoring did not contribute significantly (p > 0.05) to the variation of any of the 3 indices. All 3 indices detected differences among patients (p < 0.01). Differences between visits were detectable with SLEDAI (p = 0.04) but not with SLAM or BILAG: CONCLUSION: Our study confirms that the SLEDAI, SLAM and BILAG are comparable disease activity measures. SLEDAI appears to be sensitive to change in disease activity over time. PMID- 7983649 TI - Digital pressure responses to cooling in patients with suspected early vs definite scleroderma (systemic sclerosis) vs primary Raynaud's phenomenon. AB - OBJECTIVE: To compare digital vascular responses to local finger cooling in 4 groups of subjects: patients with definite scleroderma (SD, systemic sclerosis) meeting ARA criteria (n = 16), patients with suspected early SD (n = 12), patients with primary Raynaud's phenomenon (RP) (n = 23) and a control group of 29 healthy subjects. METHODS: Their digital systolic pressures were measured at 30, 20, 15 and 10 degrees C finger cuff temperature, in a room kept at 18 degrees C. RESULTS: The results of the digital pressure measurements showed a clearcut difference between the SD, primary RP and control groups, but there was no difference between patients with definite SD and those with suspected early SD. CONCLUSION: Under our experimental conditions, digital pressure response to local cooling separates groups of patients with primary RP and those with secondary RP related to SD from each other and from controls. The similarity between digital pressure responses of patients with suspected early SD and those with definite SD, suggests an early organic involvement of the digital vasculature in SD. PMID- 7983650 TI - Micronutrient antioxidant status in patients with primary Raynaud's phenomenon and systemic sclerosis. AB - OBJECTIVE: To investigate the possibility that micronutrient antioxidant status is an important factor in determining the severity of Raynaud's phenomenon (RP) and in differentiating between patients with primary Raynaud's phenomenon (PRP) and those in whom Raynaud's is secondary to systemic sclerosis (SSc). METHODS: Four micronutrient antioxidants (selenium, vitamin E, beta-carotene and ascorbic acid) and 2 "markers" of free radical associated activity were assayed in peripheral blood from 10 patients with PRP, 9 with limited cutaneous SSc (ISSc), 9 with diffuse SSc (dSSc) and 15 healthy control subjects. RESULTS: Plasma ascorbic acid was reduced in all 3 groups of patients: median level 10.6 mg/l in controls, 4.8 mg/l in PRP (p < 0.01), 2.5 mg/l in ISSc (p < 0.01) and 6.8 mg/l in dSSc (p < 0.05). A reduction in serum selenium was especially found in dSSc (median 75 micrograms/l compared to 100 micrograms/l in controls, p < 0.05). In keeping with these deficiencies, the serum concentration of 9, 11, linoleic acid was elevated in RP patients: median values for the molar ratio of the isomer to the parent fatty acid were 1.91% in controls, 3.70% in ISSc (p < 0.05) and 3.85% in dSSc (p < 0.01). Smoking patients showed lower levels of ascorbic acid and higher levels of the linoleic isomer than nonsmokers. CONCLUSION: Deficiencies of ascorbic acid and selenium may predispose towards irreversible tissue injury in RP patients and cigarette smoke may be an independent risk factor. Micronutrient antioxidant supplements may be of therapeutic value. PMID- 7983651 TI - Rheumatic diseases in China: ILAR-China study comparing the prevalence of rheumatic symptoms in northern and southern rural populations. AB - OBJECTIVE: To determine the prevalence of rheumatic diseases in Han Chinese in north and south China. METHODS: Samples of 4192 adults in the Beijing (north) and 5057 in the Shantou (south) areas, based on village administration registers, were studied. The same questionnaire was administered by doctors who then examined those with rheumatic symptoms. One observer (QYZ) took part in both studies. RESULTS: The prevalence of definite rheumatoid arthritis (RA) was 0.34% (95% CI; 0.20-0.51) in the north and 0.32% (0.16-0.47) in the south. Ankylosing spondylitis (AS) was noted in 0.26% of both samples (95% CI; 0.11-0.42 north and 0.14-0.40 south). Only 3 cases of systemic lupus erythematosus (SLE) in the north and one in the south were identified. General rheumatic pain was reported more frequently in the north. Lumbar problems were recorded on examination 5 times more frequently in the north than in the south [men, 25%:5.3%; women 38%:6.5%] and knee problems 10 times more frequently [men, 24%:1.8%; women, 36%:3.4%] in the north. The difference was greatest in the 55 to 64 year age group. CONCLUSION: The prevalence of RA was similar to that in other rural populations and Japan, but only half that reported from other industrialized communities. The prevalence of AS was similar to that in most Caucasian populations. SLE was too infrequent to establish a prevalence with confidence, but did not differ from that in other populations. A study is planned in the south to assess the contribution of interobserver error and/or differences in cultural response to the north/south differences observed in the prevalence of general rheumatic symptoms and back pain. PMID- 7983652 TI - Experimental arthritis and uveitis in rats associated with Mycobacterium butyricum. AB - OBJECTIVE: To determine if the anterior uveitis associated with adjuvant arthritis (AA) in the rat can be passively transferred with arthritis to syngeneic recipients using spleen cells or T cell lines prepared from animals given complete Freund's adjuvant (CFA) and Mycobacterium butyricum (M. butyricum) in incomplete Freund's adjuvant (IFA). METHODS: Spleen cells from Lewis or Lewis SsN rats given IFA, CFA, type I collagen in IFA (CI-IFA), or type II collagen in IFA (CII-IFA) were administered to naive rats or rats treated with pertussis toxin or bacterial endotoxin. Three CD4+ T cell lines, propagated from CFA injected rats and maintained in vitro with M. butyricum (M-1), bovine proteoglycan (PR-1) or an extract of M. butyricum (MBE-1) were administered to naive or immunosuppressed rats. The arthritogenic and uveitogenic properties of these cell preparations and intradermal MBE-IFA, CII-IFA and intraperitoneal (ip) M. butyricum without adjuvant were evaluated. RESULTS: Uveitis was observed in 15/69 (22%) arthritic rats given CFA. Spleen cells prepared from CFA injected rats caused arthritis in 55 (82%) and uveitis in 2 (3%) of 67 cell recipients. Uveitis occurred in 2/6 cell recipients pretreated with bacterial endotoxin. Neither uveitis nor arthritis was observed in rats given IFA (0/6) or spleen cells prepared from rats given IFA (0/27), CI-IFA (0/6), or CII-IFA (0/28). CII IFA produced polyarthritis in 5/6 rats, but no uveitis. CII-IFA induced arthritis associated uveitis in 1/15 animals receiving spleen cells from rats given CII IFA, but not those given CI-IFA (0/3) or IFA (0/13). Uveitis was observed in one recipient of the M-1 T cell line and in 2 recipients of the PR-1 T cell line. Immunization with 400 micrograms of MBE-IFA induced uveitis but not arthritis in 3/11 animals. The MBE specific T cell line was neither arthritogenic nor uveitogenic. A high frequency (5/6) of uveitis accompanied arthritis in male Lewis rats given ip M. butyricum. Arthritis occurred in 4/10 female Lewis rats given ip M. butyricum and 2 arthritic animals also developed uveitis. CONCLUSION: Uveitis occurs infrequently in arthritic rats given spleen cells from CFA injected animals. The ip administration of M. butyricum constitutes a novel disease model in which the immunopathological relationships between arthritis and uveitis may be more reliably studied. PMID- 7983653 TI - The polymerase chain reaction detects B cell clonalities in patients with Sjogren's syndrome and suspected malignant lymphoma. AB - OBJECTIVE: To investigate the usefulness of the polymerase chain reaction (PCR) to detect B cell clonal expansions in tissues where lymphoproliferative disease was suspected in the course of Sjogren's syndrome (SS). METHODS: Tissue samples from 7 patients with definite (5 cases) or probable (2 cases) SS were subjected to routine histopathologic studies, immunophenotyping, and genotypic analysis, including Southern blotting and PCR amplification of immunoglobulin heavy chain (IgH) variable-diversity-joining (VDJ) region gene rearrangements. RESULTS: Malignant lymphoma was detected in 3 cases, and myoepithelial sialadenitis in the remaining 4. B cell clonal expansion was detected in 7/7 cases by PCR, 5/7 by Southern blotting, and in no case of myoepithelial sialadenitis by kappa/lambda light chain immunophenotyping. CONCLUSION: PCR may represent a quick and powerful tool to detect B cell clonalities in SS. Such information may provide new insights into the pathogenesis of the disease and may improve the clinical approach to the patients. PMID- 7983654 TI - Fibroblast function in psoriatic arthritis. I. Alteration of cell kinetics and growth factor responses. AB - OBJECTIVE: To explore the potential role of fibroblasts in the pathogenesis of psoriasis and its related arthritis. Specifically, we analyzed the cell cycle of psoriatic fibroblasts obtained from skin and synovium by flow cytometry, and we also studied their response to several growth factors. METHODS: Fibroblast cultures were established from normal and psoriatic skin, uninvolved and involved, and synovium. NIH-3T3 cells were also used as indicator cells in some of the experiments. Fibroblasts DNA cell cycle analysis was performed by flow cytometry, and the data was analyzed by using the "Cytologic DNA applications software version 2." In addition, fibroblasts were stimulated with growth factors including epidermal growth factor, transforming growth factor-beta, and platelet derived growth factor. RESULTS: A significant increase of S and G2-M phase values in confluent cultures of psoriatic fibroblasts in both skin and synovium compared to normal fibroblasts was found. Psoriatic fibroblasts also exhibited a greater proliferative response to growth factors compared to normal fibroblasts. CONCLUSION: Data obtained clearly showed a significant intrinsic in vitro alteration in skin and synovium fibroblasts from patients with psoriasis. PMID- 7983656 TI - Arthropathica ulcerosa: a study of reduced ankle movement in association with chronic leg ulceration. AB - OBJECTIVE: To quantify the clinical impression that reduced ankle movement occurs in association with chronic lower leg ulceration, to obtain data on the relation between severity and duration, and to assess the role of other factors such as age, smoking, and lipodermatosclerosis. METHODS: Ipsilateral and contralateral passive range of movement (ROM) of the tibiotalar joint were measured in 38 patients with chronic ulceration of the lower leg. Passive ROM in 40 elderly patients without venous ulceration was also measured. Subjects with chronic ulceration had a mean duration of current ulceration of 3.4 years but a mean total duration of ulcer disease of 19.2 years. RESULTS: A significant difference in passive ROM was noted between ipsilateral and contralateral legs (ROM ipsilateral leg 36.3 +/- 10 degrees; ROM contralateral leg 45.3 +/- 13 degrees, t = -3.27, p = 0.002). No significant difference in equilibrium position at the ankle was observed between normal and affected legs. Multiple regression analysis revealed that for every year of life the patient lost 0.36 degree of tibiotalar movement and for every year of active ulceration the patient lost 0.78 degree of movement. This restriction of movement was not associated with the presence of lipodermatosclerosis nor with smoking history. CONCLUSION: A reduction in movement in the dorsovolar plane occurs in the ankle joint adjacent to chronic ulceration and, the longer the period of ulceration, the greater the restriction of movement. PMID- 7983655 TI - Fibroblast function in psoriatic arthritis. II. Increased expression of beta platelet derived growth factor receptors and increased production of growth factor and cytokines. AB - OBJECTIVE: The main objective was to investigate the expression of platelet derived growth factor (PDGF) receptors, and production of growth factors and cytokines from psoriatic skin and synovium derived fibroblasts. METHODS: Fibroblast cultures were established from normal and psoriatic skin and synovium. Confluent cultures of fibroblasts were used for a receptor binding assay for PDGF, and then extracts were run on Western blot. The amount of immunoreactive A and B chain peptides present was determined with specific A or B chain antisera. Production of interleukin 1 beta and PDGF-beta was accomplished by neutralization with the use of commercially available antisera. A functional assay was used to measure transforming growth factor-beta (TGF-beta). RESULTS: There was an increased expression of the beta PDGF receptor in the psoriatic fibroblasts. Interleukin 1 beta and PDGF-beta production by psoriatic fibroblasts was also increased. However, TGF-beta production was similar in normal and psoriatic fibroblasts. CONCLUSION: Our data demonstrate an increased expression of beta PDGF receptor, and production of IL-1 beta and PDGF by psoriatic fibroblasts. The findings provide further support for an active role of this cell line in the pathogenesis of psoriasis and psoriatic arthritis. PMID- 7983657 TI - Familial hypokalemia/hypomagnesemia and chondrocalcinosis. AB - OBJECTIVE: Familial occurrence of Bartter's syndrome is well known, but the simultaneous occurrence of hypokalemia/hypomagnesemia and chondrocalcinosis in one family has not been described. We present the clinical, laboratory and radiological findings of a family, in which 7 members were affected by disease. METHODS: A total of 43 members of the family could be interviewed concerning their general health, past diseases and joint complaints. Serum potassium and magnesium were determined in all and radiographic studies were performed in those who had hypokalemia and hypomagnesemia or those with merely articular complaints. Urinary excretion of potassium, magnesium and calcium were determined in the affected persons. RESULTS: Seven patients were found with hypokalemia and hypomagnesemia. Urinary potassium and magnesium excretion was inappropriately high when compared to the serum levels of these electrolytes. All patients had hypocalciuria and extensive chondrocalcinosis, mainly in the knees, elbows and shoulders. In one patient, most probably as a result of magnesium supplementation, a striking reduction of chondrocalcinosis was observed during a followup of 10 years. CONCLUSION: A family with familial hypokalemia/hypomagnesemia and chondrocalcinosis is described. The reduction of chondrocalcinosis, after years of magnesium supplementation in one patient, suggests that hypomagnesemia is an important factor in the pathogenesis of chondrocalcinosis in these patients. PMID- 7983658 TI - The C6-7 syndrome--clinical features and treatment response. AB - OBJECTIVES: (1) To confirm association of marked tenderness at the coracoid tip, lateral pectoral and medial elbow sites, with tenderness at the C6-7 level in the cervical spine. This had been observed in subjects with prior neck pain, who lost tenderness at C5-6 and standard upper body sites with neck support during sleep, but remained symptomatic; (2) to document apparent risk and prognostic factors; (3) to observe the effects of a modified treatment strategy. METHODS: A protocol including possible risk and prognostic factors was developed, and a case series assembled. Findings on entry tested the hypothesized pattern of linked tender sites. Subjects consenting to followup became a cohort in which outcomes were studied. RESULTS: In 151 subjects, there were associations among the tenderness scores (mean r value of 0.59, p < 0.001) of points in the 6-7 group on the same side, an intermediate level of association with contralateral but homologous points (mean r value of 0.31), but weak associations (mean r value 0.07) with contralateral and different points. During followup, 47% obtained marked or complete relief at their first followup visit, and a final followup (median 18 months), 84% of those without previous fibromyalgia (FM) achieved this satisfactory outcome, and 63% of those with prior FM. CONCLUSION: This experience supports the hypothesis that mechanical factors determine patterns of symptoms and tenderness in many subjects with regional and general pain syndromes, and points to new strategies of diagnosis and treatment which may be critical for success. PMID- 7983660 TI - Appendicular bone mass and osteoarthritis of the hands in women: data from the Baltimore Longitudinal Study of Aging. AB - OBJECTIVE: The association of appendicular bone mass with hand osteoarthritis (OA) was studied in 238 Caucasian female participants aged 40 and above in the Baltimore Longitudinal Study of Aging. METHODS: Bilateral hand radiographs taken between 1978 and 1991 were read for grade of OA using Kellgren-Lawrence scales. Two measures of appendicular bone mass, percent cortical area of the second metacarpal and bone mineral density of the distal radius measured with single photon absorptiometry, were assessed at the same visit. RESULTS: Bivariate analyses showed that increasing grade of hand OA was associated with increasing age and decreasing bone mass as measured by both techniques. After adjustment for age and body mass index, however, neither of these measures of appendicular bone mass remained significantly associated with grade of hand OA. CONCLUSION: Our data fail to support the hypothesis that increased appendicular bone mass is associated with hand OA in women. PMID- 7983659 TI - Chronic fatigue syndrome--a controlled cross sectional study. AB - OBJECTIVE: To look for signs of immunodeficiencies and/or longstanding infections underlying chronic fatigue syndrome (CFS). METHODS: Twenty-one patients fulfilling the Centers for Disease Control criteria for CFS were compared to 21 age and sex matched controls. A number of viral antibodies as well as the following tests evaluating the immune system were studied: autoantibody profile, cell surface markers on isolated blood mononuclear cells, cytokine production, lymphocyte proliferative responses, natural killer cell activity and quantitation of immunoglobulin secreting cells. RESULTS: Production in vitro of the predominantly T cell derived cytokines interleukin 2 and interferon gamma was significantly higher in patients with CFS compared to the control group. Furthermore, the serum concentrations of IgA and IgE were lower in patients with CFS; however, this difference was caused by a larger number with values of IgA and IgE above the upper limit of the normal range among the controls than among the patients with CFS. All other variables were similar in the 2 groups. CONCLUSION: A pathogenically significant imbalance of the immune system in patients with CFS cannot be excluded. However, evidence of a causal link between abnormal immunity and CFS was not obtained. PMID- 7983661 TI - A comparison of 6 months' compliance of patients with rheumatoid arthritis treated with tenoxicam and naproxen. Use of patient computer data to assess response to treatment. AB - OBJECTIVE: To assess longterm compliance in patients with rheumatoid arthritis (RA) of 20 mg tenoxicam or 500-1000 mg naproxen taken daily and to evaluate patient computer data collection. METHODS: Three hundred and seven patients were treated in a double blind, randomized multicenter study for 6 months. The first 4 weeks of treatment data were collected daily via patient operated computers in parallel with standard assessment at weekly visits to the clinics. RESULTS: Daily patient data collection was more sensitive than weekly clinical assessments. Six months' compliance was 62% for tenoxicam and 67% for naproxen with comparable rates of withdrawal due to lack of efficacy or adverse drug experiences in both groups. The spectra of adverse drug events found were very similar for both drugs but the rates were higher than in short term studies. CONCLUSION: Daily computer data collection by patients is superior to classical clinical evaluation in drug studies. The longterm compliance of tenoxicam and naproxen are comparable when treating patients with RA. PMID- 7983662 TI - Experimental articular toxicity of aluminum compounds in vivo. AB - OBJECTIVE: To investigate the articular toxicity of 2 aluminum derivatives, one insoluble (hydroxide) and/or the other soluble (lactate), after a single administration in rabbits and rats. METHODS: First, aluminum levels in plasma, urine, synovial tissue, liver and kidney were measured in saline treated rabbits and 1 to 2 days after an articular injection of 75 mg of aluminum compounds into their right knee. The methodology used was argon plasma emission spectrometry. Thereafter, the joint toxicity of aluminum lactate at the same dose regimen was evaluated for 2 days by a qualitative histological examination of synovial tissue and articular surfaces and a colorimetric assay (1,9-DMB) of patellar articular cartilage proteoglycan content. Secondly, the single injection of 50 mg of aluminum derivatives as an inducer of inflammation was studied in the rat subcutaneous air pouch, a model for a synovial-like space. Leukocytes and eicosanoids levels were measured in pouch washout fluids from 1 to 72 h after injection. RESULTS: After injection into rabbit knee, aluminum lactate largely distributed within the body while hydroxide remained locally. However, aluminum lactate resulted in perivascular edema, sparse infiltration of inflammatory cells in the synovium and a hemorrhagic effusion. Proliferation of the synovial cell layer coexisted with an apparent loss of proteoglycan in superficial zones of tibial and femoral cartilages when patellar proteoglycan content remained unchanged. Aluminum hydroxide did not affect joint structures. In the air pouch experiment, aluminum lactate increased prostaglandin E2 (PGE2) levels from 3 to 10 h after its injection and less intensively leukotriene B4 (LTB4) levels after 6 h, in the absence of leukocytes migration into the cavity. In contrast, aluminum hydroxide increased leukocytes count in pouch-washout fluid from 3 to 24 h after its injection when PGE2 and LTB4 levels were little modified. CONCLUSION: Although some differences attributable to dissimilarities in the experimental model used, aluminum compounds, even in a soluble form, may damage joint structures either directly or through stimulating the secretion of eicosanoids by synovial-like cells. PMID- 7983663 TI - Seroprevalence of Helicobacter pylori infection is not increased in pediatric inflammatory arthritides. AB - OBJECTIVE: To determine the seroprevalence of H. pylori infection among children with inflammatory arthritides receiving antiinflammatory drug therapy. METHODS: An enzyme linked immunosorbent assay (ELISA) was used to detect H. pylori specific immunoglobulin G antibody in 95 children with inflammatory arthritides, 53 children with chronic inflammatory bowel diseases and 47 parents of children with inflammatory arthritis. RESULTS: The frequency of seropositivity in children with arthritis (9/95, 9.5%) was not significantly higher than in children with chronic inflammatory bowel diseases (1/53, 1.9%; p = 0.16). Serum samples from parents were positive in 16 of 47 (34%), including 4 parents with children who also demonstrated a positive immune response. CONCLUSION: These data do not provide evidence for an increased frequency of H. pylori infection among children with inflammatory arthritides. The therapeutic use of ulcerogenic medications is likely to be an independent risk factor predisposing to dyspeptic symptoms and gastritis in this patient population. PMID- 7983664 TI - Demography of a regional pediatric rheumatology patient population. Affiliated Children's Arthritis Centers of New England. AB - OBJECTIVE: To examine the descriptive epidemiology of a regional cohort of children with rheumatic disease, and to document the variety and frequency of diseases encountered among pediatric rheumatology centers. METHODS: Pediatric rheumatology centers in southern New England participated in a prospective multicenter patient registry. All outpatients attending clinics at 8 pediatric rheumatology centers were enrolled as subjects during the 8-year period of study (n = 4585). Diagnostic criteria defined the rheumatic disease cases which were determined by clinical examination by a pediatric rheumatologist, and record linkage was achieved to avoid duplication of subjects. RESULTS: Rheumatic conditions were diagnosed in 1742 subjects. Juvenile rheumatoid arthritis (JRA) was the most frequently encountered rheumatic condition (53%), followed by spondyloarthropathy syndromes (13%), vasculitis (10%), systemic lupus erythematosus (SLE) (6%), isolated Raynaud's phenomenon (5%), dermatomyositis/polymyositis (DM/PM) (5%), and scleroderma (2%). The mean annual incidence of JRA, spondyloarthropathy syndromes, SLE and DM/PM among children referred to pediatric rheumatology centers in Massachusetts was 4.0, 2.0, 0.4 and 0.4 per 100,000 children at risk, respectively. Nonrheumatic conditions were diagnosed in 2843 subjects, among which musculoskeletal conditions were most frequent (56%) followed by infectious disorders (18%), psychogenic disorders (3%), fever of unknown origin (2%), and abnormal immune serology without a specific diagnosis (2%). CONCLUSION: The use of a multicenter patient registry was successful in allowing the collection of descriptive epidemiologic data on a large and well defined sample of children with rare disorders. PMID- 7983665 TI - Active lupus and preeclampsia: a life threatening combination. AB - A patient with active systemic lupus erythematosus presented with generalized convulsions and acute myocardial infarction during the first trimester. Serial determinations of biochemical variables and liver histology indicated that preeclampsia might be responsible for the life threatening episodes. PMID- 7983666 TI - Onset of polymyositis with autoantibodies to threonyl-tRNA synthetase during pregnancy. AB - A 24-year-old black woman developed polymyositis with autoantibodies to threonyl tRNA synthetase in the 2nd trimester of her 3rd pregnancy. This was complicated by fetal loss and the development of severe relapsing myositis resistant to corticosteroid and azathioprine therapy. These features were also common in other cases in the literature. Antisynthetase antibodies had not been reported in myositis occurring during pregnancy and may be of interest regarding the pathogenesis of inflammatory myopathy complicating pregnancy. PMID- 7983667 TI - Fasciitis (not scleroderma) following prolonged exposure to an organic solvent (trichloroethylene). AB - We describe 2 cases of diffuse fasciitis with eosinophilia (DFE) associated with prolonged exposure to the industrial solvent trichloroethylene (TCE). The medical and personal histories, examinations, and laboratory and pathological investigations were reviewed and summarized. The 2 case reports, representing the first and 2nd cases of DFE associated with TCE, were compared with 8 reported cases of systemic sclerosis associated with TCE and suggest a direct association between TCE exposure and the development of fasciitis (DFE). PMID- 7983668 TI - A swinging heart in limited systemic sclerosis. AB - We describe a 3rd patient with limited cutaneous systemic sclerosis (ISSc) complicated by a pericardial effusion sufficient to cause hemodynamic compromise. Although more commonly appreciated as a complication of diffuse systemic sclerosis, the recognition of hemodynamically compromising pericardial effusion presenting in the limited form of ISSc can be lifesaving. PMID- 7983669 TI - Piroxicam induced pulmonary infiltrates and eosinophilia. AB - We describe 2 patients who developed pulmonary infiltrates while being treated with piroxicam. There was no satisfactory explanation other than drug induced lung disease for their illness. They had no exposure to pneumotoxic drugs or aerocontaminants. Microorganisms were not cultured in sputum or bronchoaveolar lavage. There was no underlying illness with possible lung involvement. Pulmonary infiltrates developed during piroxicam therapy, disappeared after drug withdrawal and recurred following rechallenge. PMID- 7983670 TI - Disabling fibromyalgia: appearance vs reality. PMID- 7983671 TI - Disabling fibromyalgia: appearance vs reality. PMID- 7983672 TI - Decreased perception threshold to electrocutaneous stimulation in a patient with fibromyalgia. PMID- 7983673 TI - The use of methylprednisolone pulse therapy in a severe case of HLA-B27 negative ankylosing spondylitis. PMID- 7983675 TI - Polyarteritis nodosa (PAN) with coronary aneurysms: the kawasaki-PAN controversy revisited. PMID- 7983674 TI - Is spinal tuberculosis back again in developed countries? PMID- 7983676 TI - Biphasic modulation of protein kinase C (PKC) activity by polychlorinated dibenzo p-dioxins (PCDDs) in serum-deprived rat aortic smooth muscle cells. AB - Previous studies in this laboratory have shown that benzo(a)pyrene (BaP) modulates protein kinase C (PKC)-mediated phosphorylation of aortic smooth muscle cell (SMC) proteins. This observation is consistent with the ability of other aromatic hydrocarbons (AHs), such as 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), to modulate kinase activities in cells of hepatic, testicular, and thymic origin. Because all these chemicals share the ability to bind the aryl hydrocarbon receptor (AhR), the present studies were conducted to determine if changes in PKC activity by AHs conform with established structure-activity relationships. Experiments were conducted to examine the effects of TCDD, 2,3,7,8 tetrachlorodibenzofuran (TCDF), and 2,8-dichlorodibenzodioxin (DCDD) on the phosphorylation of exogenous histone type-III under basal and PKC-activating conditions. These congeners exhibit both high (TCDD and TCDF) and low (DCDD) AhR agonist activities. Measurements of kinase activity were conducted in the cytosolic and particulate fractions of growth-arrested (i.e., serum-deprived) cultured rat aortic SMCs incubated with 10 nM TCDD, TCDF, and DCDD for 0.5, 12, or 24 hours. No changes in basal kinase activity were induced by these chemicals at any of the times tested. Significant decreases in cytosolic and particulate PKC activity relative to controls were observed upon exposure of SMCs for 0.5 hours to 10 nM TCDD, TCDF, and DCDD. In contrast, SMCs exposed to TCDD and TCDF for 12 hours exhibited a significant increase in PKC activity in both cytosolic and particulate fractions. The PKC activity in cells exposed to DCDD for 12 hours was not altered.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7983677 TI - Inhibition of S-(1,2-dichlorovinyl)-L-cysteine-induced lipid peroxidation by antioxidants in rabbit renal cortical slices: dissociation of lipid peroxidation and toxicity. AB - Precision-cut, rabbit renal slices were used to examine the effects of three novel antioxidants (U-74006, U-74500, and U-78517) on S-(1,2-dichlorovinyl)-L cysteine (DCVC)-induced lipid peroxidation and toxicity. Slices exposed to DCVC showed a dose- and time-dependent increase in lipid peroxidation (TBARS) and a decrease in cellular viability, as evidenced by the loss of intracellular potassium, during the course of a 3 hour incubation. Subsequent studies employed DCVC concentrations of 100 microM. Microemulsion formulations of U-78517, U 74500, and U-74006 (100 microM) inhibited DCVC-induced lipid peroxidation by 100 +/-, 50 +/-, and < 5% (not significant), respectively. However, none of these antioxidants had a significant effect on DCVC-dependent cytotoxicity, as indicated by intracellular potassium release. The effects of U-78517, the most potent of the three antioxidants, were similar to those observed with two model antioxidants, diphenyl-p-phenylenediamine (DPPD) and the iron chelator, deferoxamine. Aminooxyacetic (AOAA), an inhibitor of renal cysteine conjugate beta-lyase, had only a minimal effect on DCVC-induced lipid peroxidation, and no effect on toxicity. These data represent the first report of DCVC-induced lipid peroxidation in rabbit renal cortical slices, a system which has been widely used to investigate mechanisms of nephrotoxicity, including that induced by DCVC. Our results demonstrate that DCVC-induced lipid peroxidation in renal slices can be inhibited by a variety of antioxidant compounds operating by different mechanisms. Because inhibition of lipid peroxidation had minimal effect on DCVC dependent cytotoxicity, the data suggest that DCVC-induced lipid peroxidation is not a major mechanism in the cytotoxicity induced by this compound. PMID- 7983678 TI - Autoprotection: stimulated tissue repair permits recovery from injury. AB - Autoprotection is a phenomenon whereby prior exposure to a small dose of a chemical results in protection against a subsequently administered lethal dose of the same compound. While CCl4 autoprotection has been studied the most, it has also been demonstrated for other chemicals. Recent studies indicate that the prevailing concept of decreased bioactivation of the normally lethal dose of CCl4 owing to decreased hepatic microsomal cytochrome P-450 content cannot be supported by direct end points of liver injury such as necrosis. These findings suggest a pivotal role for hepatocellular division and tissue healing processes stimulated by the protective dose in the mechanism of autoprotection. Augmentation of hepatocellular regeneration and tissue repair, stimulated by the protective dose, appears to permit timely recovery and restoration of hepatic structure and function. In the absence of the protective dose, hepatocellular division is substantially deficient and it occurs too late to tip the delicate balance between recovery from injury and progression of massive injury in favor of recovery. Abolition of autoprotection by colchicine antimitosis, under conditions where metabolism and disposition of CCl4 are not altered, is supportive of this concept. Selective colchicine antimitotic suppression of the early phase of hepatocellular division and tissue repair induced by a low dose of CCl4 results in progression of toxic liver injury, leading to hepatic failure and mortality. Studies have shown that pretreatment with phenobarbital results in postponed low-dose CCl4-stimulated cell division by 24 hours, which accordingly postpones the optimal autoprotection.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7983679 TI - Long-lasting effects of chronic ethanol administration on the activity of antioxidant enzymes. AB - The aim of this study was to investigate the long-lasting effects of prolonged administration of ethanol doses on oxidative processes of aged rats. We determined the activity of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) in erythrocytes of rats 15, 20, and 24 months old treated with an average daily dose of 1.5 g/Kg of ethanol or saline administered intraperitoneally for 13 weeks and after a 2 month period of withdrawal from treatment. The activity of all three enzymes decreased significantly with aging in the controls, while no age-related changes were found among treated rats. These findings are important since they are the first to show a long-lasting toxic effect of low ethanol doses observed in association with the aging process. PMID- 7983680 TI - Partial characterization of neuropathy target esterase and related phenyl valerate esterases from bovine adrenal medulla. AB - The mechanism by which organophosphorus-induced delayed polyneuropathy is induced relates to the specific inhibition and subsequent modification ("aging") of a protein known as neuropathy target esterase (NTE), operatively defined as paraoxon-resistant and mipafox-sensitive phenyl valerate (PV) esterase activity. This protein has fundamentally been investigated in hen brain, the latter being the habitually employed OPIDP study model. In the present article, a partial characterization is made of the NTE and other related PV esterases in the bovine adrenal medulla and brain; NTE sensitivity to the neurotoxic organophosphorus compound mipafox is investigated, and its subcellular distribution is studied. The NTE activity of the adrenal medulla was found to be the highest of those among the tissues studied to date (5000 +/- 1400 mU/g tissue; +/- SD, n = 12). This activity represented 93% of the PV esterase activity resistant to 40 microM paraoxon in the particulate fraction of the adrenal medulla and approximately 50% of total PV esterase activity. In the bovine brain, these proportions were 72 and 26%, respectively, i.e., similar to those described in hen brain. The mipafox inhibition curve of PV esterase activity resistant to 40 microM paraoxon in the particulate fraction of the adrenal medulla suggests that NTE activity fundamentally comprises a mipafox-sensitive component with an I50 of 6.39 microM at 30 minutes, which is similar to the value reported in hen brain. NTE activity in the bovine adrenal medulla is almost exclusively limited to the particulate fraction, the microsomal fraction, plasma membrane, and chromaffin granule enriched fractions being the highest in terms of specific activity.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7983681 TI - Characterization of the acyl-CoA:amino acid N-acyltransferases from primate liver mitochondria. AB - The acyl-CoA:amino acid N-acyl-transferases were partially purified from human liver mitochondria. The aralkyl transferase (ArAlk) had glycine conjugating activity toward the following compounds: benzoyl-CoA > butyryl-CoA, salicylyl-CoA > heptanoyl-CoA, indoleacetyl-CoA. Its kinetic properties and responses to salt were very similar to those of bovine ArAlk. Further, its molecular weight was found to be similar to that of the bovine enzyme, in contrast to reports from other laboratories. Thus, it was concluded that the human and bovine ArAlk are not significantly different. The human arylacetyl transferase (AAc) had glutamine conjugating activity toward phenylacetyl-CoA, but only 3-5% as much activity toward indoleacetyl-CoA or 1-naphtylacetyl-CoA, respectively. While this was similar to the bovine AAc, the two forms differed in several respects. First, the human liver AAc was insensitive to salts. Second, glycination of phenylacetyl-CoA by human AAc could only be detected at a high concentration of glycine (50 mM), and the rates were < 2% of the rate of glutamination. In contrast, glycine conjugation predominates with bovine AAc. Kinetic analysis of the glutamination of phenylacetyl-CoA by human AAc revealed a KD for phenylacetyl-CoA of 14 microM and a Km for glutamine of 120 mM. These values indicate that the human AAc is not more efficient at glutamination than the AAc from bovine liver. An AAc was purified from rhesus monkey liver and found to have similar kinetic constants to the human form. This indicates that nonprimate enzymes do not have a defect in glutamine conjugation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7983682 TI - Significance of TCDD-induced changes in protein phosphorylation in the adipocyte of male guinea pigs. AB - The chemical TCDD (2,3,7,8-tetrachlorodibenzo-p-dioxin) at very low concentrations has been found to cause a rapid rise in protein phosphorylation activities in the extranuclear fraction (i.e., cytosol and cellular membranes) of the adipose tissue from male guinea pigs. The effect occurred both in vivo and when TCDD was added to adipose in tissue culture (in situ). To study the cause for such a TCDD-induced biochemical change, isolated adipose tissues were treated with TCDD in conjunction with various diagnostic agents known to affect protein synthesis (actinomycin D and cycloheximide) and protein phosphorylation activities (genistein). The stimulatory effect of TCDD on protein phosphorylation was not totally abolished by actinomycin D; however, cycloheximide and genistein partially suppressed the effect of TCDD. Such an action of TCDD was accompanied by a quick rise in ras GTP binding activity as well as a rise in phosphorylation of nuclear c-myc protein product within 10 minutes after TCDD addition, indicating that TCDD is likely to activate the signal transduction pathway for growth factors. In view of the absence of an inhibitory action of actinomycin D and the short time required for TCDD to induce these changes, we have formulated a working hypothesis that stimulation of protein phosphorylation activities by TCDD may not be mediated by a transcriptional process. To test this possibility, an extranuclear fraction was obtained from the homogenate of adipose tissue, and the effect of TCDD was studied in vitro cell- and nucleus-free conditions. It was found that TCDD was capable of activating protein phosphorylation activity under cell free conditions even in the absence of nuclei. Such an action of TCDD is dependent on the action of the Ah receptor. PMID- 7983683 TI - Sensitivity toward visual impairment. PMID- 7983684 TI - Retinopathy of prematurity: diagnosis and management [continuing education credit]. AB - 1. Despite advancements in neonatal and ophthalmic care, over 500 infants per year are blinded by retinopathy of prematurity (ROP). 2. Cryotherapy and laser photocoagulation have greatly improved the prognosis for infants with ROP. 3. Despite timely intervention, some infants with ROP will develop retinal detachment. PMID- 7983685 TI - Soft toric lenses fitting for the ophthalmic technician. AB - 1. Many ophthalmic technicians are familiar with fitting standard soft lenses that correct hyperopia and myopia. There is less confidence, however, in their proficiency with fitting soft toric lenses that correct astigmatism. 2. Performing accurate keratometry and refraction is an essential first step in fitting soft toric lenses. Familiarity with the different types of toric lenses is integral to an effective fit. 3. Knowledge of front and back surface toric lenses and their indications is of primary concern and allows for an effortless and successful fit. PMID- 7983686 TI - Eye disease among the impressionists: Monet, Cassatt, Degas, and Pissarro. AB - 1. Many of the most famous artists working in France late in the 19th century suffered serious eye diseases. 2. The case reports of Monet, Cassatt, Degas, and Pissarro are interesting because of the light they shed on important artists and their methods of dealing with adversity. 3. These case reports also can be useful in consoling patients who have similar problems today. PMID- 7983687 TI - Corneas for the Kikiyu: procurement of tissue in East Africa. AB - 1. By introducing a viable donor tissue procurement, the International Eye Bank has increased the supply of corneal tissue for Kikiyu Mission Hospital's Eye Unit. 2. Tissue procurement can be realistically handled in off-peak times in the United States. 3. The use of modern communication, an excellent surgical staff and well-maintained surgical equipment, and the generosity of medical volunteers and pharmaceutical suppliers have made this project successful. PMID- 7983688 TI - Identifying the nonmedical concerns of patients with ocular melanoma. AB - 1. The task of enhancing patients' quality of life begins with identifying their needs and concerns. This process requires a knowledge base of the needs, problems, and barriers patients face as they struggle with the physical, psychological, and social sequelae of cancer. 2. To enhance knowledge of the psychosocial consequences of ocular melanoma and to facilitate supportive care planning, a study was initiated to identify patients' needs arising from the symptom management and nonmedical concerns of these patients, barriers to resolving these needs, and patients' service preferences. 3. The results indicate that the expressed needs inventory and the scales measuring unexpressed needs represent a valid and reliable approach to needs assessment, and that this approach is able to identify the needs resulting from patients' symptom management and nonmedical concerns. PMID- 7983689 TI - Self-assessment quiz. Coloboma of the optic nerve and retina. PMID- 7983691 TI - Perspective on contact lenses. Increasing compliance by reducing complexity. PMID- 7983690 TI - Silicone oil as a vitreous substitute in vitreoretinal surgery. PMID- 7983692 TI - Study on the children of Kaohsiung with acute viral infection of lower respiratory tract by direct immunofluorescence assay. AB - This study retrospectively reviewed those pediatric patients of acute lower respiratory tract infection with positive virus identification by direct immunofluorescence assay (Direct IF) from Jan, 1992 to Dec, 1993. One hundred and eighteen patients with 133 positive Direct IF results (107 cases with single virus identified, and 11 cases with more than one) were included. The sex ratio was 1.6:1 with males predominant; age, 22.1 (1 approximately 154.8) (months); duration of admission, 5.7 (1 approximately 69) (days); peripheral white blood cell count, 10,600 +/- 3,800/mm3; C-reactive protein, 17.0 (0 approximately 163.3) mu/ml; body temperature, 37.1 +/- 1.1 degrees C in those cases with single virus. The symptoms were cough 105 cases (98.1%), rhinorrhea 46 cases (43.0%), dyspnea and/or tachypnea 43 cases (40.2%) and diarrhea 15 cases (14.0%). The viruses identified were: Adenovirus (52 cases, 39.1%). Influenza B (45 cases, 33.8%), Parainfluenza 1 (28 cases, 20.1%), Parainfluenza 3 (19 cases 14.3%), Respiratory Syncytial virus (17 cases, 12.8%), and Influenza A (9 cases, 6.8%). The seasonal incidence rates were spring (49 cases, 36.8%), summer (46 cases, 34.6%), autumn (23 cases, 17.3%), and winter (15 cases, 11.3%). The results showed much similarity with others, except the commonest viral type (Adenovirus in this study; Respiratory Syncytial virus in others) and the seasonal incidence rate (higher in spring and summer in this study but not in others). In conclusion, most children with acute viral lower respiratory tract infection had an uneventful course and Direct IF is a reliable method for viral detection in that disease. PMID- 7983693 TI - Stressors, personality and mental health: a follow-up study. AB - One hundred and two Taiwanese subjects participated in a questionnaire follow-up study. Measurements of stressors (major life events, minor daily hassles and perceived stress of university life), personality (locus of control, extraversion and neuroticism) and mental health (depression, anxiety and somatic symptoms) were taken at Time 1; mental health was measured again at Time 2 eight months later. Using multivariate analyses, we found that (1) depressive, anxiety and somatic symptoms were all quite stable over an 8-month period; (2) daily hassles could still predict somatic symptoms at Time 2; and (3) locus of control could also predict anxiety symptoms at Time 2. Impacts of life events and daily hassles and the roles of personality in the stress process are discussed. PMID- 7983694 TI - [Effect of aminoglycoside on ascending auditory pathway evaluated by evoked potentials]. AB - Permanent ototoxic injuries frequently occur after long term administration of aminoglycosides (AGs). An attempt was made to evaluate the effects of AGs on both peripheral and central auditory systems in rats by brainstem auditory evoked potentials (BAEPs). A total of 43 Wistar rats were divided into 4 groups, and 4 kinds of AGs (gentamicin, tobramycin, amikacin and streptomycin) were applied respectively to rats in each group with IM injection daily for 9 weeks. BAEPs were recorded pre- and post-injection weekly. Rats with gentamicin administration had no apparent changes in peak latencies until 7 weeks when prolongations occurred. Tobramycin administration in rats caused peak latencies to prolong progressively. Prolongations of peak latencies initially followed by no more evident changes were present in rats with amikacin or streptomycin. However, few consistent changes in interpeak latencies were shown in all rats. These results indicate that ototoxicity occurs at the peripheral auditory system, and the involvement of central auditory pathway was uncertain. PMID- 7983695 TI - [Drug resistance and plasmid analysis in Pseudomonas aeruginosa]. AB - One hundred and ninety seven strains of Pseudomonas aeruginosa were isolated from urine (59 strains), wound pus (60 strains), sputum (30 strains), stool (30 strains) and eye discharge (18 strains) at Kaohsiung medical College Hospital. These strains were serotyped with antisera against O antigens and tested with twelve different antimicrobial agents. The results showed that the most frequently isolated strains were serotype E (41.1%), followed by serotype B (20.3%), serotype F (10.7%) and serotype L (9.1%). In in vitro susceptibility testing, all isolated strains were resistant to chloramphenicol and tetracycline. Otherwise, these isolates were highly susceptible to ceftazidime (95.4%), enoxacin (89.3%) and piperacillin (87.8%). The isolates from urine exhibited more multiple drug resistance patterns than those of other specimens. When plasmid content was analysed from pseudomonas aeruginosa, only 15.2% (30/197) of isolates carried plasmids. By conjugation, transformation and mobilization experiments, it was shown that 13.3% (4/30) of plasmid carrying strains contained R plasmids. PMID- 7983696 TI - Malignant pheochromocytoma associated with Jaccoud's-type arthropathy, Raynaud's phenomenon, positive antinuclear antibody and rheumatoid factor. AB - We describe a patient with malignant pheochromocytoma who developed Jaccoud's type arthropathy and Raynaud's phenomenon as initial manifestations of malignant pheochromocytoma. Serologic findings included positive antinuclear antibody (ANA) and rheumatoid factor (RF) was also found in this patient. To our knowledge, this is the first time Jaccoud's-type arthropathy with positive ANA and RF has been reported as rheumatic manifestations of pheochromocytoma. PMID- 7983697 TI - Pleomorphic adenoma of the lung--report of a case and review of the literature. AB - A male patient, aged 36, was found to have lower lobe collapse of the left lung. A smooth vascularized whitish nodular mass obstructing the orifice of left common basal bronchus was noted through bronchoscopic examination. After left lower lobectomy, the histological features of the tumor were indistinguishable from those of the pleomorphic adenoma of the salivary gland. To our knowledge, only 12 cases of pulmonary pleomorphic adenoma have been reported in the literature. PMID- 7983698 TI - Thallium myocardial scintigraphy in single left coronary artery. AB - A case of single left coronary artery is presented with the correlation between the results of thallium-201 (T1-201) myocardial single photon emission computed tomography (SPECT) and coronary angiographic findings. The chest pain in this case might be partly secondary to the myocardial ischemia, under stress, which could result from the steal phenomenon to normal perfusion myocardium due to anatomical anomaly of single left coronary artery. Our findings suggest that T1 201 myocardial SPECT could be a useful method for detecting myocardial ischemia in patients with single left coronary artery. PMID- 7983699 TI - [Biliary ascariasis--a case report]. AB - A 60-year-old male suffered from abdominal pain, chills and fever for two weeks. A vivid Ascaris lumbricoides in the common bile duct and intrahepatic ducts was identified in operation. Chronic cholecystitis was also noted. We discuss the findings of multiple image modalities in biliary ascariasis and review the literature. PMID- 7983700 TI - A switch region determines the cell type-specific positive or negative action of YY1 on the activity of the human papillomavirus type 18 promoter. AB - YY1 is a zinc finger transcription factor which acts as either a repressor or an activator dependent on the promoter context. YY1 is a potent activator of the genuine human papillomavirus type 18 (HPV-18) upstream regulatory region (URR) in HeLa cells, which are known for high-level expression of the HPV-18 early genes. The activating activity of YY1 is dependent on the presence of a newly identified switch region located upstream of the YY1 binding site. Deletion of this region causes YY1 to act as a repressor of HPV-18 promoter activity. In vivo footprinting of the HPV-18 URR and an in vitro electrophoretic mobility shift assay identified proteins binding to the switch region. Site-directed mutagenesis of the switch region and YY1 binding sites suggests that these two regions work in concert to yield high-level HPV-18 URR activity in HeLa cells but not in HepG2 cells, where HPV-18 is almost inactive. These data identified a novel mode of cell type-specific regulation of HPV-18 promoter activity by positive or negative action of YY1, determined by the switch region binding factor(s). PMID- 7983701 TI - Inhibition of human immunodeficiency virus type 1 replication by a Tat-activated, transduced interferon gene: targeted expression to human immunodeficiency virus type 1-infected cells. AB - We have examined the feasibility of using interferon (IFN) gene transfer as a novel approach to anti-human immunodeficiency virus type 1 (HIV-1) therapy in this study. To limit expression of a transduced HIV-1 long terminal repeat (LTR) IFNA2 (the new approved nomenclature for IFN genes is used throughout this article) hybrid gene to the HIV-1-infected cells, HIV-1 LTR was modified. Deletion of the NF-kappa B elements of the HIV-1 LTR significantly inhibited Tat mediated transactivation in T-cell lines, as well as in a monocyte line, U937. Replacement of the NF-kappa B elements in the HIV-1 LTR by a DNA fragment derived from the 5'-flanking region of IFN-stimulated gene 15 (ISG15), containing the IFN stimulated response element, partially restored Tat-mediated activation of LTR in T cells as well as in monocytes. Insertion of this chimeric promoter (ISG15 LTR) upstream of the human IFNA2 gene directed high levels of IFN synthesis in Tat expressing cells, while this promoter was not responsive to tumor necrosis factor alpha-mediated activation. ISG15-LTR-IFN hybrid gene inserted into the retrovirus vector was transduced into Jurkat and U937 cells. Selected transfected clones produced low levels of IFN A (IFNA) constitutively, and their abilities to express interleukin-2 and interleukin-2 receptor upon stimulation with phytohemagglutinin and phorbol myristate acetate were retained. Enhancement of IFNA synthesis observed upon HIV-1 infection resulted in significant inhibition of HIV-1 replication for a period of at least 30 days. Virus isolated from IFNA producing cells was able to replicate in the U937 cells but did not replicate efficiently in U937 cells transduced with the IFNA gene. These results suggest that targeting IFN synthesis to HIV-1-infected cells is an attainable goal and that autocrine IFN synthesis results in a long-lasting and permanent suppression of HIV-1 replication. PMID- 7983702 TI - RNA binding properties of poliovirus subviral particles. AB - The mechanism of encapsidation of the RNA genome of poliovirus and other picornaviruses is unknown. To test whether any of the putative assembly intermediates of poliovirus could interact directly with the poliovirus RNA genome, poliovirus RNA was attached to magnetic streptavidin beads and incubated with partially purified extracts containing 35S-labeled 14S pentamer and 75S empty-capsid subviral particles from infected cells. The amount of labeled protein bound to the beads was monitored, thus testing the RNA-binding activities of only the labeled viral proteins in the preparations. In this assay, nonspecific RNA-binding activity was displayed by the 14S pentameric particles and mature virons. 75S empty capsids displayed no propensity to associate with RNA. 14S pentamers were demonstrated to form rapidly sedimenting complexes and to undergo a conformational alteration upon RNA binding. These findings are consistent with a direct role for the 14S pentameric particles in RNA packaging during poliovirus morphogenesis. PMID- 7983703 TI - Efficient system of homologous RNA recombination in brome mosaic virus: sequence and structure requirements and accuracy of crossovers. AB - Brome mosaic virus (BMV), a tripartite positive-stranded RNA virus of plants engineered to support intersegment RNA recombination, was used for the determination of sequence and structural requirements of homologous crossovers. A 60-nucleotide (nt) sequence, common between wild-type RNA2 and mutant RNA3, supported efficient repair (90%) of a modified 3' noncoding region in the RNA3 segment by homologous recombination with wild-type RNA2 3' noncoding sequences. Deletions within this sequence in RNA3 demonstrated that a nucleotide identity as short as 15 nt can support efficient homologous recombination events, while shorter (5-nt) sequence identity resulted in reduced recombination frequency (5%) within this region. Three or more mismatches within a downstream portion of the common 60-nt RNA3 sequence affected both the incidence of recombination and the distribution of crossover sites, suggesting that besides the length, the extent of sequence identity between two recombining BMV RNAs is an important factor in homologous recombination. Site-directed mutagenesis of the common sequence in RNA3 did not reveal a clear correlation between the stability of predicted secondary structures and recombination activity. This indicates that homologous recombination does not require similar secondary structures between two recombining RNAs at the sites of crossovers. Nearly 20% of homologous recombinants were imprecise (aberrant), containing either nucleotide mismatches, small deletions, or small insertions within the region of crossovers. This implies that homologous RNA recombination is not as accurate as proposed previously. Our results provide experimental evidence that the requirements and thus the mechanism of homologous recombination in BMV differ from those of previously described heteroduplex-mediated nonhomologous recombination (P. D. Nagy and J. J. Bujarski, Proc. Natl. Acad. Sci. USA 90:6390-6394, 1993). PMID- 7983704 TI - Identification of a Rev-related protein by analysis of spliced transcripts of the human endogenous retroviruses HTDV/HERV-K. AB - The human endogenous retrovirus family HTDV/HERV-K codes for the viral particles observed in teratocarcinoma cell lines. Two types of proviral genomes exist; these differ in the presence or absence of a stretch of 292 nucleotides. This sequence comprises the amino-terminal part of the env gene, the putative signal peptide, which overlaps in part with the carboxy terminus of the pol gene. Type 2 genomes containing this sequence presumably more closely reflect the structure of the infectious, replication-competent retrovirus ancestors of the HERV-K family than do type 1 genomes that lack the sequence. In human teratocarcinoma cell lines, both variants are expressed. Type 1 genomes, in which pol and env genes are fused, are deficient in splicing. Type 2 transcripts are spliced to subgenomic env mRNA and smaller messages. A doubly spliced transcript encodes a short open reading frame, preliminarily designated cORF (R. Lower, K. Boller, B. Hasenmeier, C. Korbmacher, N. Mueller-Lantzsch, J. Lower, and R. Kurth, Proc. Natl. Acad. Sci. USA 90:4480-4484). The genomic organization of cORF resembles that of nonprimate lentivirus rev genes: the first exon comprises nearly the entire signal peptide of env, and the second exon is derived from a different reading frame in the 3' part of the genome. A nucleolar localization signal, which is also a putative RNA binding domain, as well as a sequence with similarities to the Rev effector domain consensus sequence is present in the first exon. Secondary structure analysis reveals similarities to basic helix-loop helix proteins. cORF is a small protein with an apparent molecular mass of 14 kDa which accumulates in the nucleolus as has been described for Rev proteins. PMID- 7983705 TI - Differential Epstein-Barr virus gene expression in B-cell subsets recovered from lymphomas in SCID mice after transplantation of human peripheral blood lymphocytes. AB - We have analyzed the human B-cell tumors that arise spontaneously in SCID mice who have been given transplants of peripheral blood lymphocytes from Epstein-Barr virus (EBV)-seropositive donors to determine if patterns of EBV gene expression are correlated with phenotypic changes in the tumor B cells. Tumor cells were separated into two B-cell subsets by cell sorting on the basis of differential coexpression of membrane CD23 and CD38. One subset showed intermediate levels of CD23 and CD38 expression (CD23intCD38int), while a second subset had low-level CD23 but high-level CD38 expression (CD23loCD38hi). The CD23intCD38int cells had a high proliferative index and secreted little immunoglobulin in vitro; the CD23loCD38hi cells had a low proliferative index and high-level immunoglobulin secretion. We next analyzed the sorted cells for viral transcripts associated with latency (EBNA-1, EBNA-2, and LMP-1) or lytic cycle replication (ZEBRA and gp350 envelope protein). Only latent cycle transcripts were found in CD23intCD38int cells, whereas lytic cycle transcripts and transforming virus were present in the CD23loCD38hi cells. Finally, we generated short-term cell lines from the sorted CD23intCD38int cells and transferred these cells to SCID recipients. The resulting secondary tumors were predominantly CD23loCD38hi, suggesting that the CD23intCD38int lymphoblastoid cells are precursors to the well-differentiated, plasmacytoid CD23loCD38hi cells. These observations are discussed in the context of a three-step model for EBV-associated lymphomagenesis in humans. PMID- 7983706 TI - Early transcription of the ie-1 transregulator gene of Autographa californica nuclear polyhedrosis virus is regulated by DNA sequences within its 5' noncoding leader region. AB - The ie-1 gene of Autographa californica nuclear polyhedrosis virus (AcMNPV) encodes a transregulatory protein (IE1) which accelerates the expression of early and late virus genes. Transcription of ie-1 occurs immediately upon infection from a conserved CAGT motif and continues into the late phases. To examine the mechanisms by which ie-1 expression is regulated, cis-acting control elements within the ie-1 promoter were identified by constructing hybrid early promoters and by using site-directed mutagenesis. The ie-1 upstream activating region, extending from nucleotide -546 to the TATA element at -34, stimulated ie-1 basal promoter activity more than 1,000-fold when transfected into uninfected Spodoptera frugiperda SF21 cells. However, when introduced into the genome of AcMNPV recombinants, the ie-1 upstream activating region had only a minimal twofold effect early in infection. Instead, maximum steady-state levels of early ie-1 RNAs required sequences within the 5' noncoding leader region extending from +11 to +24 relative to the RNA start site (+1). The +11 to +24 noncoding region did not influence the stability of ie-1 transcripts. When assayed by in vitro transcription, deletion of the +11 to +24 region reduced the levels of ie-1 runoff RNAs. Thus, this downstream activating sequence controlled the rate of early ie-1 transcription. A larger overlapping region from +11 to +36 affected steady-state levels of ie-1 RNAs late (24 h) in infection. Deletion of sequences that included the conserved CAGT start site abolished early ie-1 transcription. Thus, ie-1 is the first example of an early baculovirus gene in which essential cis-acting regulatory elements reside within the 5' noncoding region and include sequences comprising the RNA start site. PMID- 7983707 TI - Determinants of human immunodeficiency virus type 1 entry in the CDR2 loop of the CD4 glycoprotein. AB - Various roles for the viral receptor, CD4, have been proposed in facilitating human immunodeficiency virus type 1 (HIV-1) entry, including virion binding to the target cell and the induction of conformational changes in the viral envelope glycoproteins required for the membrane fusion reaction. Here, we compare the structural requirements in the CDR2-like loop of CD4 domain 1, the major contact site of the gp120 envelope glycoprotein, for gp120 binding and virus entry. For every CD4 mutant examined, the level of cell surface expression and the gp120 binding affinity were sufficient to explain the relative ability to function as a viral receptor. The decrease in relative infectibility associated with decreased gp120 binding affinity was more pronounced at lower cell surface CD4 concentrations. These results imply that both receptor density and affinity determine the efficiency of HIV-1 entry and that specific structures in the CD4 residues examined are probably not required for HIV-1 entry functions other than gp120 binding. PMID- 7983709 TI - CCAAT box-dependent activation of the TATA-less human DNA polymerase alpha promoter by the human cytomegalovirus 72-kilodalton major immediate-early protein. AB - Human cytomegalovirus (HCMV) immediate-early (IE) proteins are known potent transregulators of viral and cellular gene expression upon HCMV infection. HCMV is known to activate a number of cellular genes intimately associated with the cell cycle and DNA replication by mechanisms involving the viral major IE 86-kDa protein (IE2). We have recently shown that IE2 mediates this activation in a TATA dependent manner and interacts directly with the TATA-binding protein. However, a number of TATA-less cellular promoters, e.g., DNA polymerase alpha and dihydrofolate reductase, are also activated by HCMV infection. Consequently, we have asked how HCMV mediates this activation. We show that, consistent with its known TATA dependency, IE2 does not activate the DNA polymerase alpha promoter. In contrast, this promoter is strongly activated by the major IE 72-kDa protein (IE1). Whilst deletion of ATF or E2F sites within the DNA polymerase alpha promoter had little effect on IE1-mediated activation, removal of the CCAAT box appeared to abolish high levels of activation by IE1. Consistent with this observation, we also find that IE1 interacts directly with the CCAAT box binding factor CTF1 in vitro and massively augments CTF1-mediated activation of the DNA polymerase alpha promoter in transient transfection assays. PMID- 7983708 TI - The adenovirus E3 10.4K and 14.5K proteins, which function to prevent cytolysis by tumor necrosis factor and to down-regulate the epidermal growth factor receptor, are localized in the plasma membrane. AB - The adenovirus type 2 and 5 E3 10,400- and 14,500-molecular-weight (10.4K and 14.5K) proteins are both required to protect some cell lines from lysis by tumor necrosis factor and to down-regulate the epidermal growth factor receptor. We have shown previously that both 10.4K and 14.5K are integral membrane proteins and that 14.5K is phosphorylated and O glycosylated. The 10.4K protein coimmunoprecipitates with 14.5K, indicating that the two proteins function as a complex. Here we show, using immunofluorescence and two different cell surface labeling techniques, that both proteins are localized in the plasma membrane. In addition, we show that trafficking of each protein to the plasma membrane depends on concomitant expression of the other protein. Finally, neither protein could be immunoprecipitated from conditioned media, indicating that neither is secreted. Taken together, these results suggest that the plasma membrane is the site at which 10.4K and 14.5K function to inhibit cytolysis by tumor necrosis factor and to down-regulate the epidermal growth factor receptor. PMID- 7983710 TI - Substrate determinants for cleavage in cis and in trans by the hepatitis C virus NS3 proteinase. AB - Processing of the hepatitis C virus polyprotein is accomplished by a series of cotranslational and posttranslational cleavages mediated by host cell signalases and two virally encoded proteinases. Of these the NS3 proteinase is essential for processing at the NS3/4A, NS4A/4B, NS4B/5A, and NS5A/5B junctions. Processing between NS3 and NS4A occurs in cis, implying an intramolecular reaction mechanism, whereas cleavage at the other sites can also be mediated in trans. Sequence analysis of the amino termini of mature cleavage products and comparisons of amino acid residues around the scissile bonds of various hepatitis C virus isolates identified amino acid residues which might contribute to substrate specificity and processing efficiency: an acidic amino acid at the P6 position, a Thr or Cys at the P1 position, and a Ser or Ala at the P1' position. To study the importance of these residues for NS3-mediated cleavage we have undertaken a mutational analysis using an NS3'-5B polyprotein expressed by recombinant vaccinia viruses in mammalian cells. For all NS3-dependent cleavage sites P1 substitutions had the most drastic effects on cleavage efficiency, showing that amino acid residues at this position are the most critical substrate determinants. Since less drastic effects were found for substitutions at the P1' position, these residues appear to be less important for proper cleavage. For all cleavage sites the P6 acidic residue was dispensable, suggesting that it is not essential for substrate recognition and subsequent cleavage. Analysis of a series of mutations at the NS3/4A site revealed great flexibility for substitutions compared with more stringent requirements at the trans cleavage sites. On the basis of these results we propose a model in which processing in cis is determined primarily by polyprotein folding, whereas cleavage in trans is governed not only by the structure of the polyprotein but also by specific interactions between the proteinase and the polyprotein substrate at or around the scissile bond. PMID- 7983711 TI - An autoregulated dual-function antitat gene for human immunodeficiency virus type 1 gene therapy. AB - One approach to gene therapy for AIDS is to block the replication of human immunodeficiency virus type 1 (HIV-1) by inhibiting that tat gene, whose product activates the expression of all HIV-1 genes. To accomplish this, we constructed an antitat gene expressing an RNA with dual (polymeric TAR and antisense-tat) function in an attempt to both sequester Tat protein and block its translation from mRNA. A minigene consisting of the antitat gene driven by the HIV-1 long terminal repeat was inserted into a double-copy retrovirus vector, such that antitat expression would be upregulated only in HIV-1-infected cells. After transduction of a T-lymphocytic cell line (Molt-3) the antitat gene inhibited HIV 1 replication. This inhibition was inversely correlated with the virus infections dose. Virus replication was also inhibited for 5 months in two different T-cell lines after they had been infected at a high multiplicity of infection, suggesting that the antitat gene may be effective over long periods. Importantly, antitat blocked the replication and the cytopathic effect of HIV-1 in human peripheral blood mononuclear cells and led to as much as 4,000-fold inhibition of the replication of an HIV-1 field isolate as well as HIV-1 prototypes maintained in culture. These results suggest that antitat gene therapy has potential use for blocking HIV-1 replication in infected individuals. PMID- 7983712 TI - Lymantria dispar nuclear polyhedrosis virus homologous regions: characterization of their ability to function as replication origins. AB - Homologous regions (hrs) were identified in the Lymantria dispar nuclear polyhedrosis virus (LdMNPV) genome. A 1.58-kb region surrounding hr4 was sequenced and found to have two distinct domains. Domain I (about 600 bp) is composed of seven repeats of about 80 bp including a series of palindromes containing MluI sites and overlapping XhoI and SacI sites. Domain II (about 700 bp) is composed of eight partially repeated sequences of 60 to 100 bp containing a 15- to 25-bp sequence that is 80 to 100% A+T in addition to a 6- to 10-bp palindrome containing an NruI site. Hybridization of a domain I sequence to cosmids containing the LdMNPV genome indicated its presence at eight positions (hr1 to -8) on the genome. In contrast, hybridization of domain II indicated that it was present only at the hr4 locus. A DpnI-based transient-replication assay was used to determine if subclones of hr4 transfected into LdMNPV-infected L. dispar cells functioned as replication origins. Subclones of hr4 containing either domain I or domain II replicated at very low or moderate levels, respectively. However, when domain I and domain II were linked on the same plasmid, high levels of replication were observed. A 1.4-kb region containing hr1 was also sequenced. It lies immediately upstream of the polyhedrin gene and contains six domain I-type repeats. Four-hundred-base-pair regions of domain I repeats from hr1 and hr4 showed 89% sequence identity. Plasmids containing the hr1 domain I replicated at low levels. However, hybrid plasmids in which the AT rich hr4 domain II was inserted adjacent to hr1 domain I replicated to high levels, indicating that the AT-rich domain II greatly enhances replication. The orientation and position of domains I and II relative to each other did not have major effects on the levels of replication. PMID- 7983714 TI - Immortalization of human B lymphocytes by a plasmid containing 71 kilobase pairs of Epstein-Barr virus DNA. AB - We have assembled derivatives of Epstein-Barr Virus (EBV) that include 71 kbp of noncontiguous DNA sequences cloned into a prokaryotic F-factor plasmid. These mini-EBVs, when introduced into an EBV-containing lymphoblastoid cell, can be packaged by the endogenous helper virus. One such mini-EBV was found to have a single C residue deleted from its EBNA3a open reading frame. When packaged, this mini-EBV initiates proliferation of infected primary human B lymphocytes only in conjunction with a complementing helper virus. Proliferation of the infected cells, however, was maintained either alone by the mini-EBV containing the mutated EBNA3a open reading frame or alone by its derivative in which the EBNA3a open reading frame had been healed of its lesion by recombination with the helper virus. The mini-EBV with a wild-type EBNA3a open reading frame when packaged alone can both initiate and maintain proliferation upon infection of primary human B lymphocytes. These findings identify 41% of EBV DNA which is sufficient to immortalize primary human B lymphocytes and provide an assay to distinguish virus contributions to initiation or maintenance of cell proliferation or both. They also identify EBNA3a as a transforming gene, which contributes primarily to the initiation of cell proliferation. PMID- 7983715 TI - NF-Y controls transcription of the minute virus of mice P4 promoter through interaction with an unusual binding site. AB - Electrophoretic mobility shift assays performed with nuclear extracts from human fibroblasts revealed the formation of two major protein complexes with an oligonucleotide (nucleotides 78 to 107) from the palindromic region located upstream from the minute virus of mice (MVM) P4 promoter. It was shown that this oligonucleotide bound USF at the enhancer E box CACATG. The second complex contained the transcription factor NF-Y, whose association was surprising because its target sequence lacks the canonical CCAAT motif present in all mammalian NF-Y binding sites identified so far. The MVM NF-Y recognition element instead contains the CCAAC sequence. USF and NF-Y had distinct but overlapping sequence requirements for binding, suggesting that their associations with MVM DNA were mutually exclusive. Because of the palindromic nature of MVM DNA terminal sequences, NF-Y associated with the three nucleotide configurations corresponding to the hairpin structure and to the external and internal arms of the extended duplex replication form, respectively. However, owing to the imperfection of the palindrome, the binding of USF was restricted to the internal arm. Point mutations that suppressed the in vitro binding of NF-Y to the internal palindromic arm reduced the activity of the resident P4 promoter, while those preventing complex formation with USF did not, as determined by transient expression assays using the luciferase reporter gene. The data led to the identification of a novel P4 upstream regulatory region capable of interacting with two transcription factors, from which one (NF-Y) appeared to upmodulate the activity of the promoter. PMID- 7983713 TI - Pol gene quasispecies of human immunodeficiency virus: mutations associated with drug resistance in virus from patients undergoing no drug therapy. AB - The nucleotide sequences of two pol gene regions (codons 41 to 108 and 181 to 219 of reverse transcriptase) of 60 human immunodeficiency virus type 1 genomes obtained directly from primary lymphocytes from infected individuals are reported. In addition, the mutant spectra of several quasispecies have been sampled by repetitive sequencing of molecular clones representing the same pol genomic regions. Average mutation frequencies ranged from 1.6 x 10(-2) to 3.4 x 10(-2) substitutions per nucleotide for independent samples (relative to their consensus nucleotide sequence) and from 3.6 x 10(-3) to 1.1 x 10(-2) substitutions per nucleotide for individual quasispecies distributions. Several mutations leading to amino acid substitutions related to loss of sensitivity to reverse transcriptase inhibitors have been identified in samples from patients not subjected to antiretroviral therapy. Mutation frequencies in the codons previously identified as involved in resistance to reverse transcriptase inhibitors were very similar to the average mutation frequencies in the pol region analyzed. Thus, the finding of mutations related to drug resistance (even in the absence of positive selection by the corresponding drugs) is the expected consequence of the statistical distribution of mutations along the pol gene. The presence of such critical amino acid replacements in human immunodeficiency virus type 1 populations underscores the importance of viral quasispecies as reservoirs of phenotypic virus variants and has a number of implications for AIDS control. PMID- 7983716 TI - Defective RNA replication by poliovirus mutants deficient in 2A protease cleavage activity. AB - 2A protease (2Apro) catalyzes the initial cleavage of the poliovirus polyprotein which separates the P1 structural protein precursor from the P2-P3 nonstructural protein precursor. In addition, 2Apro indirectly induces cleavage of the p220 component of eukaryotic initiation factor 4F, which is thought to contribute to the specific inhibition of host cell protein synthesis observed in virus-infected HeLa cells. However, it is unclear whether the trans function of 2Apro which induces host cell shutoff is essential or merely facilitates efficient poliovirus replication. In this study, three point mutations in 2Apro (D38E, Y88L, and Y89L [S. F. Yu and R. E. Lloyd, Virology 182:615-625, 1991]) which cause specific loss of trans but not cis cleavage function were independently introduced into the full-length poliovirus cDNA. In addition, mutations which caused only partial loss of both cis and trans cleavage activities (Y88S) or resulted in a wild-type phenotype (Y88F) were individually introduced. When each of these mutant poliovirus cDNAs was transcribed and translated in vitro, normal proteolytic processing of the viral polyprotein was observed, and p220 was not cleaved in those reactions containing proteases defective in trans function, as expected. Surprisingly, Northern (RNA) blot analysis and reverse transcriptase-PCRs performed after transfection of COS-7 or HeLa cells with these viral RNAs revealed that Y88S and Y88L RNAs replicated at only very low levels. RNA replication could not be detected at all in cells transfected with D38E and Y89L RNAs. Taken together, the results suggest a correlation between the function of 2Apro and productive poliovirus RNA replication in vivo that may be independent of the ability to cause p220 cleavage. PMID- 7983717 TI - Epstein-Barr virus nuclear protein 2 transactivation of the latent membrane protein 1 promoter is mediated by J kappa and PU.1. AB - Expression of the Epstein-Barr virus (EBV) latent membrane protein 1 (LMP-1) oncogene is regulated by the EBV nuclear protein 2 (EBNA-2) transactivator. EBNA 2 is known to interact with the cellular DNA-binding protein J kappa and is recruited to promoters containing the GTGGGAA J kappa recognition sequence. The minimal EBNA-2-responsive LMP-1 promoter includes one J kappa-binding site, and we now show that mutation of that site, such that J kappa cannot bind, reduces EBNA-2 responsiveness by 60%. To identify other factors which interact with the LMP-1 EBNA-2 response element (E2RE), a -236/-145 minimal E2RE was used as a probe in an electrophoretic mobility shift assay. The previously characterized factors J kappa, PU.1, and AML1 bind to the LMP-1 E2RE, along with six other unidentified factors (LBF2 to LBF7). Binding sites were mapped for each factor. LBF4 is B- and T-cell specific and recognizes the PU.1 GGAA core sequence as shown by methylation interference. LBF4 has a molecular mass of 105 kDa and is probably unrelated to PU.1. LBF2 was found only in epithelial cell lines, whereas LBF3, LBF5, LBF6, and LBF7 were not cell type specific. Mutations of the AML1- or LBF4-binding sites had no effect on EBNA-2 transactivation, whereas mutation of the PU.1-binding site completely eliminated EBNA-2 responses. A gst-EBNA-2 fusion protein specifically depleted PU.1 from nuclear extracts and bound in vitro translated PU.1, providing biochemical evidence for a direct EBNA-2-PU.1 interaction. Thus, EBNA-2 transactivation of the LMP-1 promoter is dependent on interaction with at least two distinct sequence-specific DNA-binding proteins, J kappa and PU.1. LBF3, LBF5, LBF6, or LBF7 may also be involved, since their binding sites also contribute to EBNA-2 responsiveness. PMID- 7983718 TI - Genetic diversity of the envelope glycoprotein from human immunodeficiency virus type 1 isolates of African origin. AB - The genetic diversity of the envelope glycoprotein of human immunodeficiency virus type 1 (HIV-1) isolates was studied. HIV-1 isolates were obtained from eight countries in Africa: Djibouti, Gabon, Kenya, Senegal, Somalia, Uganda, Zaire, and Zambia. The DNA sequences encoding the complete HIV-1 envelope protein were PCR amplified and sequenced. Phylogenetic relationships among the 21 sequences from this study and the 32 previously published full-length env HIV-1 sequences were determined. Twenty of the newly sequenced African isolates could be assigned to envelope subtypes A, C, D, and G. One isolate, collected in Zambia, did not belong to any of the eight previously described subtypes and may represent a prototype sequence of its envelope subtype. The phylogenetic classification of these isolates was strongly supported by bootstrapping and the congruence of trees generated by either distance methods or maximum parsimony analysis. The data presented in this study confirm the existence of several genetic subtypes within the global HIV epidemic and broaden the genetic variability previously observed for envelope subtypes. The geographic spread of different subtypes was shown to be substantial, and the notion of cocirculation of subtypes was reinforced. PMID- 7983719 TI - The effect of two closely inserted transcription consensus sequences on coronavirus transcription. AB - Insertion of an intergenic region from the murine coronavirus mouse hepatitis virus into a mouse hepatitis virus defective interfering (DI) RNA led to transcription of subgenomic DI RNA in helper virus-infected cells. Using this system, we studied how two intergenic regions in close proximity affected subgenomic RNA synthesis. When two intergenic regions were separated by more than 100 nucleotides, slightly less of the larger subgenomic DI RNA (synthesized from the upstream intergenic region) was made; this difference was significant when the intergenic region separation was less than about 35 nucleotides. Deletion of sequences flanking the two intergenic regions inserted in close proximity did not affect transcription. No significant change in the ratio of the two subgenomic DI RNAs was observed when the sequence between the two intergenic regions was altered. Removal of the downstream intergenic region restored transcription of the larger subgenomic DI RNA. The UCUAAAC consensus sequence was needed for efficient suppression of the larger subgenomic DI RNA synthesis. These results demonstrated that the downstream intergenic sequence was suppressing subgenomic DI RNA synthesis from the upstream intergenic region. We discuss possible mechanisms to account for the regulation of this suppression of subgenomic DI RNA synthesis and the ways in which they relate to the general regulation of coronavirus transcription. PMID- 7983720 TI - Dynamic organization of splicing factors in adenovirus-infected cells. AB - Adenovirus infection affects the nuclear distribution of host splicing factors. Late phase-infected cells contain discrete clusters of small nuclear ribonucleoproteins (snRNPs) that are separate from centers containing the viral 72-kilodalton DNA-binding protein (72K protein). In the present study, we demonstrate that these snRNP clusters also contain splicing factors from the SR protein family. We show that a previously described monoclonal antibody, 3C5, detects SR proteins. Furthermore, we demonstrate that late region 3 transcription occurs at a maximal rate in infected cultures in which greater than 90% of the cells contain the snRNP clusters, indicating that such cells are actively transcribing their late genes. During the onset of the late phase, the intranuclear distribution of splicing factors is very different from that seen after the late phase is established. When late viral transcription commences, cells with snRNP clusters are less prevalent than in cultures that are maintaining maximum levels of late transcription. Instead, a cell type which shows snRNPs, concentrated in foci that also contain the viral 72K DNA-binding protein is detected. This cell type disappears from cultures by 18 to 20 h after a high-multiplicity infection. These results suggest a dynamic organization of splicing factors in infected cells that can be correlated to the status of viral gene expression. Our work also provides an explanation for the differing results that have been published concerning the organization of splicing factors in the adenovirus-infected cell nucleus (L. F. Jimenez-Garcia and D. L. Spector, Cell 73:47-59, 1993). During the present study we observed that a monoclonal antibody against the SC-35 protein, which was used by Jimenez-Garcia and Spector to study the localization of the SC-35 splicing factor in adenovirus-infected cells, cross reacts with the adenovirus 72K DNA-binding protein and is thus unsuitable for this type of study. PMID- 7983721 TI - Homologous interference resulting from the presence of defective particles of human immunodeficiency virus type 1. AB - Defective particles are naturally occurring virus mutants that lack one or more genes required for viral replication. Such viruses may affect positively or negatively the symptoms of the disease. Thus, it is of great interest to measure the role played by defective particles in the process of human immunodeficiency virus (HIV) infection since accumulating evidence indicates that a great proportion of HIV genomes are defective. We used defective particles produced by two stable cellular clones (UHC-8 and UHC-18) to investigate whether they can affect replication of infectious viral particles generated by a human T-cell line transfected with a molecular HIV-1 clone. Progeny virus harvested from UHC-8 cells has no reverse transcriptase and integrase proteins, while UHC-18 has no reverse transcriptase protein. We demonstrate here that coinoculation of a T lymphoid cell line and of peripheral blood mononuclear cells with defective and infectious particles leads to a dramatic inhibition of virus replication. Defective particles do not interfere with virus production from proviral DNA. Rather, the inhibition of reinfection events seems to be their mechanism of action. This model closely parallels the in vivo conditions and demonstrates that defective particles may limit the spread of infection and progression of the disease by reducing the yield of infectious virus. PMID- 7983722 TI - A mutant v-rel with increased ability to transform B lymphocytes. AB - We observed that two strains of REV-T differ in the ability to transform bursal cells in vitro. REV-TW, with v-rel derived from a well-characterized clone and considered the prototype of the wild type, fails to generate colonies in soft agar. In contrast, REV-S2A3, derived from the S2A3 cell line, readily transforms bursal cells. With PCR, a 1,591-bp fragment containing v-rel from the REV-S2A3 provirus was cloned into plasmid pREV-0. Except for the absence of v-rel, pREV-0 is identical to pREV-TW. Five clones of pREV-PCR, each produced by an independent amplification, were obtained. The REV-PCR viruses displayed the strong transforming phenotype of REV-S2A3. Two mutations were identified in the 5' region of v-rel from REV-PCR1 to REV-PCR5: a silent mutation and a G-to-T transversion, changing the alanine at position 40 to serine. To confirm the relevance of this amino acid substitution, a 478-bp fragment containing the mutations was exchanged between REV-TW and REV-PCR1. Only the mutant viruses were able to form large colonies of bursal cells in liquid culture and to generate bursal cell colonies in soft agar. When tested on splenocytes, the wild-type viruses induced predominantly non-B-cell colonies while the mutant viruses gave origin mainly to B-cell colonies. The above results indicate that the substitution of serine for alanine at position 40 of v-Rel enhances the ability of REV-T to transform B lymphocytes in vitro. This mutation is close to the DNA binding region, and the variant v-Rel oncoprotein shows increased kappa B-binding activity, thus confirming the relevance of this property for transformation. PMID- 7983724 TI - Transfection of a differentiated human hepatoma cell line (Huh7) with in vitro transcribed hepatitis C virus (HCV) RNA and establishment of a long-term culture persistently infected with HCV. AB - T7 RNA polymerase transcripts of a putative full-length cDNA clone of hepatitis C virus type 1 (HCV-1) were used to transfect a differentiated human hepatoma cell line, Huh7. The transfected genome replicated in cells, as evidenced by the appearance of progeny HCV RNA, detection of negative-strand viral RNA, and incorporation of [3H]uridine into the viral genome. Incubation of naive Huh7 cells with conditioned medium from transfected cells resulted in a new HCV infection, suggesting the production of biologically active virus in the inoculum. Maintenance of the transfected cells under serum-free culture conditions resulted in the selection of persistently infected cells which displayed a distinctive cellular morphology. This is the first demonstration that HCV RNA produced from cloned HCV cDNA is infectious and replication competent. This approach should provide a valuable system for studying HCV replication, persistence, and pathogenicity. PMID- 7983723 TI - Infection of central nervous system cells by ecotropic murine leukemia virus in C58 and AKR mice and in in utero-infected CE/J mice predisposes mice to paralytic infection by lactate dehydrogenase-elevating virus. AB - Certain mouse strains, such as AKR and C58, which possess N-tropic, ecotropic murine leukemia virus (MuLV) proviruses and are homozygous at the Fv-1n locus are specifically susceptible to paralytic infection (age-dependent poliomyelitis [ADPM]) by lactate dehydrogenase-elevating virus (LDV). Our results provide an explanation for this genetic linkage and directly prove that ecotropic MuLV infection of spinal cord cells is responsible for rendering anterior horn neurons susceptible to cytocidal LDV infection, which is the cause of the paralytic disease. Northern (RNA) blot hybridization of total tissue RNA and in situ hybridization of tissue sections demonstrated that only mice harboring central nervous system (CNS) cells that expressed ecotropic MuLV were susceptible to ADPM. Our evidence indicates that the ecotropic MuLV RNA is transcribed in CNS cells from ecotropic MuLV proviruses that have been acquired by infection with exogenous ecotropic MuLV, probably during embryogenesis, the time when germ line proviruses in AKR and C58 mice first become activated. In young mice, MuLV RNA containing cells were found exclusively in white-matter tracts and therefore were glial cells. An increase in the ADPM susceptibility of the mice with advancing age correlated with the presence of an increased number of ecotropic MuLV RNA containing cells in the spinal cords which, in turn, correlated with an increase in the number of unmethylated proviruses in the DNA extracted from spinal cords. Studies with AKXD recombinant inbred strains showed that possession of a single replication-competent ecotropic MuLV provirus (emv-11) by Fv-1n/n mice was sufficient to result in ecotropic MuLV infection of CNS cells and ADPM susceptibility. In contrast, no ecotropic MuLV RNA-positive cells were present in the CNSs of mice carrying defective ecotropic MuLV proviruses (emv-3 or emv-13) or in which ecotropic MuLV replication was blocked by the Fv-1n/b or Fv-1b/b phenotype. Such mice were resistant to paralytic LDV infection. In utero infection of CE/J mice, which are devoid of any endogenous ecotropic MuLVs, with the infectious clone of emv-11 (AKR-623) resulted in the infection of CNS cells, and the mice became ADPM susceptible, whereas littermates that had not become infected with ecotropic MuLV remained ADPM resistant. PMID- 7983725 TI - Synthetic multimeric peptides derived from the principal neutralization domain (V3 loop) of human immunodeficiency virus type 1 (HIV-1) gp120 bind to galactosylceramide and block HIV-1 infection in a human CD4-negative mucosal epithelial cell line. AB - The glycosphingolipid galactosylceramide (GalCer), which binds gp120 with high affinity and specificity, is a potential alternative receptor for human immunodeficiency virus type 1 (HIV-1) in some CD4-negative neural and epithelial human cells, including the human colonic epithelial cell line HT-29. In the present study, we demonstrate that synthetic multibranched peptides derived from the consensus sequence of the HIV-1 V3 loop block HIV-1 infection in HT-29 cells. The most active peptide was an eight-branched multimer of the motif Gly-Pro-Gly Arg-Ala-Phe which at a concentration of 1.8 microM induced a 50% inhibition of HIV-1 infection in competition experiments. This peptide was not toxic to HT-29 cells, and preincubation with HIV-1 did not affect viral infectivity, indicating that the antiviral activity was not due to a nonspecific virucidal effect. Using a high-performance thin-layer chromatography binding assay, we found that multibranched V3 peptides recognized GalCer and inhibited binding of recombinant gp120 to the glycosphingolipid. In addition, these peptides abolished the binding of an anti-GalCer monoclonal antibody to GalCer on the surface of live HT-29 cells. These data provide additional evidence that the V3 loop is involved in the binding of gp120 to the GalCer receptor and show that multibranched V3 peptides are potent inhibitors of the GalCer-dependent pathway of HIV-1 infection in CD4 negative mucosal epithelial cells. PMID- 7983726 TI - Enhancer-mediated role for polyomavirus middle T/small T in DNA replication. AB - A major role for polyomavirus middle T/small T antigens in viral DNA synthesis was uncovered by examining the replication of middle T/small T-deficient mutants (hr-t mutants). hr-t mutants in the A2 genetic background showed a 16- to 100 fold defect in genome accumulation relative to the wild type when infections were carried out in exponentially growing NIH 3T3 cells in medium supplemented with low levels of serum (< 2.0%). A proportional decrease in the level of viral early transcripts was also seen. The replication defect of the hr-t mutants was partially overcome in the presence of the phorbol ester 12-O-tetradecanoylphorbol 13-acetate. The defect was also alleviated by a duplication encompassing the alpha core enhancer domain that contains binding sites for the transcriptional activators PEA1/AP-1 and PEA3/c-ets. Such a duplication is present in all naturally occurring hr-t mutants and absent in the A2 strain. The effects of 12-O tetradecanoylphorbol-13-acetate and alpha core duplication were additive but did not fully complement the absence of middle T/small T. In mixed infection competition experiments with two hr-t mutants, a genome that carried an alpha core duplication had a replication advantage (up to 17-fold) over a genome without duplication. This result demonstrates that one effect of the duplication is exerted directly at the level of DNA replication. The advantage of the duplication-bearing genome was established during the earliest stages of replication and was not further amplified in later rounds of replication. In the presence of middle T/small T, both genomes replicated to high levels and the advantage of the duplication-bearing genome was eliminated. On the basis of these results, we propose that factors that bind the alpha core domain (presumably PEA1 and PEA3) are present in limiting amounts in exponentially growing NIH 3T3 cells and play a crucial role in polyomavirus DNA replication. We further suggest that middle T and/or small T stimulates viral DNA replication by activating these factors. The fact that all middle T-/small T-defective hr-t mutants have evolved to contain enhancer duplications that encompass the PEA1 and PEA3 binding sites in the alpha core domain and partially restore their replication defect (A. Amalfitano, M. C. Chen, and M. Fluck, unpublished data) provides an adequate explanation for the fact that the importance of the role of the middle T and/or small T function in DNA replication has not been recognized previously. Much evidence is available in support of separate elements of this model.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 7983727 TI - Local expression of tumor necrosis factor alpha and interleukin-2 correlates with protection against corneal scarring after ocular challenge of vaccinated mice with herpes simplex virus type 1. AB - To correlate specific local immune responses with protection from corneal scarring, we examined immune cell infiltrates in the cornea after ocular challenge of vaccinated mice with herpes simplex virus type 1 (HSV-1). This is the first report to examine corneal infiltrates following ocular challenge of a vaccinated mouse rather than following infection of a naive mouse. Mice were vaccinated systemically with vaccines that following ocular challenge with HSV-1 resulted in (i) complete protection against corneal disease (KOS, an avirulent strain of HSV-1); (ii) partial protection, resulting in moderate corneal disease (baculovirus-expressed HSV-1 glycoprotein E [gE]); and (iii) no protection, resulting in severe corneal disease (mock vaccine). Infiltration into the cornea of CD4+ T cells, CD8+ T cells, macrophages, and cells containing various lymphokines was monitored on days 0, 1, 3, 7, and 10 postchallenge by immunocytochemistry of corneal sections. Prior to ocular challenge, no eye disease or corneal infiltrates were detected in any mice. KOS-vaccinated mice developed high HSV-1 neutralizing antibody titers (> 1:640) in serum. After ocular challenge, they were completely protected against death, developed no corneal disease, and had no detectable virus in their tear films at any time examined. In response to the ocular challenge, these mice developed high local levels of infiltrating CD4+ T cells and cells containing interleukin-2 (IL-2), IL 4, IL-6, or tumor necrosis factor alpha (TNF-alpha). In contrast, only low levels of infiltrating CD8+ T cells were found, and gamma interferon (IFN-gamma) containing cells were not present until day 10. gE-vaccinated mice developed neutralizing antibody titers in serum almost as high as those of the KOS vaccinated mice (> 1:320). After ocular challenge, they were also completely protected against death. However, the gE-vaccinated mice developed low levels of corneal disease and virus was detected in one-third of their eyes. Compared with KOS-vaccinated mice, the gE-vaccinated mice had a similar pattern of IFN-gamma, but a delay in the appearance of CD4+ T cells, CD8+ T cells, and IL-4-, IL-6-, and TNF-alpha-containing cells. In sharp contrast to those of the KOS-vaccinated mice, no cells containing IL-2 were detected in the eyes of gE-vaccinated mice at any time. Mock-vaccinated mice developed no detectable neutralizing antibody titer and were not protected from lethal HSV-1 challenge.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 7983728 TI - Cytomegalovirus protein substrates are not cleaved by the herpes simplex virus type 1 proteinase. AB - The herpesvirus maturational proteinase, assemblin, is made as a precursor that undergoes at least two autoproteolytic cleavages--one in a sequence toward its carboxyl end, called the maturational (M) site, and one in a sequence toward its midpoint, called the release (R) site. The M- and R-site sequences are both well conserved among the herpesvirus proteinase homologs, suggesting that the proteinase of one herpesvirus might be able to cleave the substrates of another. To test this possibility, we cloned and expressed in human cells the long (i.e., full-length open reading frame of proteinase gene) and short (i.e., proteolytic domain, assemblin) forms of the proteinase from human and simian cytomegalovirus (HCMV and SCMV, respectively) and from herpes simplex virus type 1 (HSV-1), as well as the genes for their respective assembly protein precursor substrates. Data from cotransfections of these proteinase genes with appropriate homologous and heterologous substrates showed that although the SCMV and HCMV enzymes cleaved the M-sites of the assembly protein substrates of all three viruses and an SCMV R-site substrate, the HSV-1 proteinase cleaved only its own substrate. This finding demonstrates that the substrate specificity properties of the HSV-1 enzyme differ from those of the two CMV enzymes. PMID- 7983729 TI - Development of physical forms of unintegrated retroviral DNA in mouse spinal cord tissue during ts1-induced spongiform encephalomyelopathy: elevated levels of a novel single-stranded form in paralyzed mice. AB - ts1 is a murine leukemia virus that causes rapidly evolving hindlimb paralysis in susceptible strains of mice. Following perinatal infection, three physical forms of unintegrated viral DNA were detected in the spinal cord by Southern blot hybridization. Linear and supercoiled closed-circle viral double-stranded DNAs were detected in both the central nervous system and non-central nervous system tissues. An elevated level of a novel minus-sense single-stranded form of viral DNA, which had a very high mobility in agarose gels, was correlated with the onset of symptoms of paralysis. As the severity of paralysis progressed, the level of this single-stranded form increased rapidly, with the highest level in the spinal cords of moribund mice. Since the virulence of a number of cytopathic retroviruses has been associated with the presence of increased amounts of unintegrated viral DNA in the tissues of the infected hosts, this novel form of highly mobile unintegrated single-stranded DNA may have a role in the neuropathogenesis of ts1. PMID- 7983730 TI - Genetic mapping of reovirus virulence and organ tropism in severe combined immunodeficient mice: organ-specific virulence genes. AB - We used reovirus reassortant genetics and severe combined immunodeficient (SCID) mice to define viral genes important for organ tropism and virulence in the absence of antigen-specific immunity. Adult SCID mice infected with reovirus serotype 1 strain Lang (T1L) died after 20 +/- 6 days, while infection with serotype 3 strain Dearing (T3D) was lethal after 77 +/- 22 days. One hundred forty-five adult SCID mice were infected with T1L, T3D, and 25 different T1L x T3D reassortant reoviruses, and gene segments associated with the increased virulence of T1L were identified. Gene segments S1, L2, M1, and L1 accounted for > 90% of the genetically determined increase in T1L virulence. Gene segment M1 was independently important for virulence, with S1, L2, and L1 alone or in combination also playing a role. T1L grew to higher titers in multiple organs and caused more severe hepatitis than T3D. Seventy adult SCID mice, T1L, T3D, and 15 T1L x T3D reassortant viruses were used to map genetic determinants of viral titers in the brain, intestines, and liver, as well as the severity of hepatitis. Different sets of gene segments were important for determining viral titers in different organs. Gene segments L1 (encoding a core protein) and L2 (encoding the core spike of the virion) were important in all of the organs analyzed. The M1 gene segment (encoding a core protein), but not the S1 gene segment, was a critical determinant of reovirus titer in the liver and severity of hepatitis. The S1 gene segment (encoding the viral cell attachment protein and a nonstructural protein), but not the M1 gene segment, was a critical determinant of titers in intestines and brains. These studies demonstrate that viral growth in different organs is dependent on different subsets of the genes important for virulence. The virion-associated protein products of the four gene segments (L1, L2, M1, and S1) important for virulence and organ tropism in SCID mice likely form a structural unit, the reovirus vertex. Organs (the brain and intestines versus the liver) differ in properties that determine which virulence genes, and thus which parts of this structural unit, are important. PMID- 7983731 TI - Human immunodeficiency virus type 1 MA deletion mutants expressed in baculovirus infected cells: cis and trans effects on the Gag precursor assembly pathway. AB - The role of the matrix protein (MA) of human immunodeficiency virus type 1 in intracellular transport, assembly, and extracellular release of Gag polyprotein precursor (Pr55gag) was investigated by deletion mutagenesis of the MA domain of recombinant Gag precursor expressed in baculovirus-infected cells. In addition, three carboxy-terminally truncated forms of the Gag precursor, representing mainly the MA, were constructed. One corresponded to an MA with a deletion of its last 12 residues (amb120), while the others corresponded to the entire MA with an additional sequence from the N-terminal portion of the CA (amb143 and och180). Deletions within the MA central region (residues 41 to 78) appeared to be detrimental to Gag particle assembly and budding from the plasma membrane. A slightly narrower domain, between amino acids 41 and 68, was found to be critical for soluble Gag secretion. Mutations which totally or partially deleted one or the other of the two polybasic signals altered the transport of N-myristylated Gag precursor to the plasma membrane. In coexpression with wild-type Gag precursor, a discrete trans-dominant negative effect on wild-type Gag particle assembly and release was observed with deletion mutants located in the central MA region (residues 41 to 78). A more significant negative effect was obtained with the two recombinant proteins of amb120 and och180, which redirected the Gag particle assembly pathway from the plasma membrane compartment to intracellular vesicles (amb120) and to the nuclear compartment (och180). PMID- 7983732 TI - Human immunodeficiency virus type 1 integrase: effects of mutations on viral ability to integrate, direct viral gene expression from unintegrated viral DNA templates, and sustain viral propagation in primary cells. AB - Integrase is the only viral protein necessary for integration of retroviral DNA into chromosomal DNA of the host cell. Biochemical analysis of human immunodeficiency virus type 1 (HIV-1) integrase with purified protein and synthetic DNA substrates has revealed extensive information regarding the mechanism of action of the enzyme, as well as identification of critical residues and functional domains. Since in vitro reactions are carried out in the absence of other viral proteins and they analyze strand transfer of only one end of the donor substrate, they do not define completely the process of integration as it occurs during the course of viral infection. In an effort to further understand the role of integrase during viral infection, we initially constructed a panel of 24 HIV-1 mutants with specific alanine substitutions throughout the integrase coding region and analyzed them in a human T-cell line infection. Of these mutant viruses, 12 were capable of sustained viral replication, 11 were replication defective, and 1 was temperature sensitive for viral growth. The replication defective viruses express and correctly process the integrase and Gag proteins. Using this panel of mutants and an additional set of 18 mutant viruses, we identified nine amino acids which, when replaced with alanine, destroy integrase activity. Although none of the replication-defective mutants are able to integrate into the host genome, a subset of them with alterations in the catalytic triad are capable of Tat-mediated transactivation of an indicator gene linked to the viral long terminal repeat promoter. We present evidence that integration of the HIV-1 provirus is essential not only for productive infection of T cells but also for virus passage in both cultured peripheral blood lymphocytes and macrophage cells. PMID- 7983733 TI - Human T-cell leukemia virus type II nucleotide sequences between env and the last exon of tax/rex are not required for viral replication or cellular transformation. AB - Human T-cell leukemia virus types I (HTLV-I) and II (HTLV-II) and bovine leukemia virus contain a region of approximately 600 nucleotides located 3' to the env gene and 5' to the last exon of the tax and rex regulatory genes. This region was originally termed nontranslated or untranslated (UT) since it did not appear to be expressed. Several studies have identified novel mRNAs in HTLV-I-, HTLV-II-, a bovine leukemia virus-infected cells that splice into open reading frames (ORFs) contained in the UT region and, thus, have the potential to produce proteins that might contribute to the biological properties of these viruses. The HTLV-II infectious molecular clone pH6neo has several ORFs in the UT region (nucleotides 6641 to 7213) and a large ORF which overlaps the third exon of tax/rex. To investigate the importance of these ORF-containing sequences on viral replication and transformation in cell culture, proviral clones containing deletions in UT (pH6neo delta UT) or a stop codon insertion mutation (pH6neoST) were constructed. Lymphoid cells were transfected with mutant proviral constructs, and stable cell clones, designated 729pH6neo delta UT and 729pH6neoST, were characterized. Viral protein production, reverse transcriptase activity, and the capacity to induce syncytia were indistinguishable from cells transfected with the wild-type clone. Finally, 729pH6neo delta UT- and 729pH6neoST-producer cells cocultured with primary blood T lymphocytes resulted in cellular transformation characteristic of HTLV. These results indicate that putative protein-coding sequences between env and the last exon of tax/rex are not required for viral replication or transformation in cell culture. PMID- 7983734 TI - Adaptation to persistent growth in the H9 cell line renders a primary isolate of human immunodeficiency virus type 1 sensitive to neutralization by vaccine sera. AB - Seven diverse primary isolates of human immunodeficiency virus type 1 (HIV-1) were examined and found to be refractory to neutralization by antisera to recombinant gp120 (rgp120) protein from HIV-1 MN. This stands in marked contrast to the sensitivity exhibited by certain laboratory-adapted viruses. To understand the difference between primary and laboratory-adapted viruses, we adapted the primary virus ACH 168.10 to growth in the FDA/H9 cell line. ACH 168.10 was chosen because the V3 region of gp120 closely matches that of MN. After 4 weeks, infection became evident. The virus (168A) replicated in FDA/H9 cells with extensive cytopathic effect but was unchanged in sensitivity to antibody-mediated neutralization. Thus, growth in cell lines is not sufficient to render primary virus sensitive to neutralization. The 168A virus was, however, partially sensitive to CD4 immunoadhesin (CD4-Ig). Adaptation was continued to produce a persistently infected FDA/H9 culture that displayed minimal cytopathic effect. The virus (168C) was now sensitive to neutralization by MN rgp120 vaccine sera and by MN-specific monoclonal antibodies and showed increased sensitivity to HIVIG and CD4-Ig. 168C encoded three amino acid changes in gp120, including one within the V3 loop (I-166-->R, I-282-->N, G-318-->R). MN-specific monoclonal antibodies bound equally to the surface of cells infected with either neutralization-resistant or -sensitive virus. The coincidence of changes in neutralization sensitivity with changes in cell tropism and cytopathic effect suggests a common underlying mechanism(s) acting through the whole of the envelope protein complex. PMID- 7983735 TI - Negative regulation of the bovine papillomavirus E5, E6, and E7 oncogenes by the viral E1 and E2 genes. AB - Papillomaviruses induce benign squamous epithelial lesions that infrequently are associated with uncontrolled growth or malignant conversion. The virus-encoded oncogenes are clearly under negative regulation since papillomaviruses can latently infect cells and since different levels of viral oncogene expression are seen within the layers of differentiating infected epitheliomas. We used bovine papillomavirus type 1 (BPV-1) to investigate the mechanisms involved in the negative regulation of transformation. We found that the following two distinct and interacting mechanisms negatively regulate BPV-1 transformation effected by virally encoded trans-acting factors: (i) E2 repressors suppress transformation by the E6 and E7 oncogenes, and (ii) E1 and the E2 transactivator suppress transformation by the E6, E7, and E5 oncogenes. These systems interact in that the E2 repressors function to relieve the transformation suppression effected by the E1 and E2 transactivator genes. A BPV-1 mutant that lacked E2 repressors and E1 had greatly augmented transformation capacity. Analysis of this mutant revealed that the enhanced transformation was due to expression of the E6 and E7 genes in the absence of E5, revealing a previously unappreciated potency and synergy for the BPV-1 E6 and E7 oncogenes. PMID- 7983737 TI - Human endogenous retrovirus K10: expression of Gag protein and detection of antibodies in patients with seminomas. AB - The human endogenous retrovirus K10 (HERV-K10) has been identified in the human genome by its homology to retroviruses of other vertebrates (M. Ono, T. Yasunaga, T. Miyata, and H. Ushikubo, J. Virol. 60:589-598, 1986). Using PCR amplification, DNA cloning, sequencing, and procaryotic expression, we were able to demonstrate that HERV-K10 encodes a 73-kDa protein which was processed by a HERV-K10-encoded protease to yield proteins p22/p26, p30, and p15/16. Analysis of the teratocarcinoma cell line Tera 1 or tumor tissues by immunoblotting demonstrated that the 80-kDa polyprotein of HERV-K10 gag and a processed protein of 39 kDa were expressed. In addition, a major protein of 39 kDa and additional species of 30, 22, 19, and 17 kDa could be detected in the supernatant of Tera 1 cells, suggesting that HERV-K10 Gag proteins are either secreted or processed to probably incomplete viral particles. In addition, the gag gene of HERV-K10 was expressed in the baculovirus system. Using this recombinant system to test antisera from patients with different diseases and healthy individuals, we were able to detect antibodies against the N-terminal part of HERV-K10 Gag in 2 to 4% of groups of tumor patients with titers ranging between 1:80 and 1:640, while approximately 0.1 to 0.5% of healthy individuals exhibited antibodies with lower titers. In contrast, patients with seminoma had antibody titers in the range of 1:2,560 at the time when the tumor was detected. Immunohistochemistry using specific rabbit sera or monoclonal antibodies against HERV-K10 Gag revealed that the Gag protein is expressed in the cytoplasm of the tumor cells. Furthermore, an 80-kDa protein corresponding to the HERV-K10 Gag polyprotein could be detected in tumor biopsies. For the first time, these data indicate that HERV-K10 Gag proteins are synthesized in seminoma cells and tumors exhibit relatively high antibody titers against Gag. So far, no information on which role HERV-K10 plays in the development of this tumor exists. PMID- 7983736 TI - The relocalization of v-Rel from the nucleus to the cytoplasm coincides with induction of expression of Ikba and nfkb1 and stabilization of I kappa B-alpha. AB - The v-Rel oncogene induces the expression of major histocompatibility complex class I and II proteins and the interleukin-2 receptor more efficiently than does c-Rel (R. Hrdlickova, J. Nehyba, and E. H. Humphries, J. Virol. 68:308-319, 1994). The kinetics with which these immunoregulatory receptors are induced in B- and T-lymphoid cell lines and chicken embryo fibroblast cultures expressing c-Rel or v-Rel have been examined. v-Rel induced the expression of major histocompatibility complex classes I and II and interleukin-2 receptor more efficiently than did c-Rel at later times after infection. In all three cell types, this increased efficiency was accompanied by a shift in the majority of v Rel from the nucleus of the cytoplasm. The concomitant relocalization of v-Rel was also demonstrated during the in vitro transformation of spleen cells. The translocation coincided with increased steady-state levels of I kappa B-alpha. Coninfection by retroviral vectors expressing v-Rel, I kappa B-alpha, or NF-kappa B1 demonstrated that either I kappa B-alpha can contribute to the shift of v-Rel to the cytoplasmic compartment. The induction of nfkb1 and Ikba mRNA and the stabilization of I kappa B-alpha by v-Rel were shown to be responsible for these effects. In comparison with c-Rel, the expression of v-Rel was associated with lower levels of transcription of these genes. However, the ability of v-Rel to stabilize I kappa B-alpha remained unchanged. The ability of v-Rel to stabilize I kappa B-alpha but poorly induce Ikba mRNA expression relative to c-Rel may play a role in regulating gene expression, thereby leading to transformation. PMID- 7983738 TI - Effect of different donor cells on human immunodeficiency virus type 1 replication and selection in vitro. AB - We sought to determine the effects of different host cells on human immunodeficiency virus type 1 (HIV-1) infection in vitro. First, 17 primary viruses of various phenotypes were examined for replicative capacity in peripheral blood mononuclear cells (PBMC) from 10 healthy donors. While the range of infection was variable over a 40-fold range, it was substantially less than that previously reported (L. M. Williams and M. W. Cloyd, Virology 184:723-728, 1991). In particular, no donor cells demonstrated total resistance to HIV-1 infection. We next cocultured PBMC from an HIV-1-infected patient with stimulated PBMC from three healthy donors to determine the effect of host cells on selection for a particular HIV-1 quasispecies. By using DNA sequencing, it was found that the dominant quasispecies (AD30-15) after culture was nearly identical in the cells of different donors. Furthermore, after 6 months in vivo, the patient developed a dominant proviral population in PBMC that was most closely related to the quasispecies preferentially selected in vitro, although this quasispecies was only a minor fraction of the sequences present earlier in PBMC. In subsequent biological characterizations, it was found that AD30-15 grew much better in PBMC and macrophages than did other related quasispecies. Hence, we conclude that the primary mechanism of in vitro selection for a particular HIV-1 variant in this case is mediated by the phenotypic properties of the virus and is less dependent on host cell origin. The findings reported here have important practical implications for studies of HIV-1 replication in primary cells derived from healthy donors. PMID- 7983739 TI - Viral RNA modulates the acid sensitivity of foot-and-mouth disease virus capsids. AB - Foot-and-mouth disease virus (FMDV) manifests an extreme sensitivity to acid, which is thought to be important for entry of the RNA genome into the cell. We have compared the low-pH-induced disassembly in vitro of virions and natural empty capsids of three subtypes of serotype A FMDV by enzyme-linked immunosorbent assay and sucrose gradient sedimentation analysis. For all three subtypes (A22 Iraq 24/64, A10(61), and A24 Cruzeiro), the empty capsid was more stable by 0.5 pH unit on average than the corresponding virion. Unexpectedly, in the natural empty capsids used in this study, the precursor capsid protein VP0 was found largely to be cleaved into VP2 and VP4. For picornaviruses the processing of VP0 is closely associated with encapsidation of viral RNA, which is considered likely to play a catalytic role in the cleavage. Investigation of the cleavage of VP0 in natural empty capsids failed to implicate the viral RNA. However, it remains possible that these particles arise from abortive attempts to encapsidate RNA. Empty capsids expressed from a vaccinia virus recombinant showed essentially the same acid lability as natural empty capsids, despite differing considerably in the extent of VP0 processing, with the synthetic particles containing almost exclusively uncleaved VP0. These results indicate that it is the viral RNA that modulates acid lability in FMDV. In all cases the capsids dissociate at low pH directly into pentameric subunits. Comparison of the three viruses indicates that FMDV A22 Iraq is about 0.5 pH unit more sensitive to low pH than types A10(61) and A24 Cruzeiro. Sequence analysis of the three subtypes identified several differences at the interface between pentamers and highlighted a His-alpha-helix dipole interaction which spans the pentamer interface and appears likely to influence the acid lability of the virus. PMID- 7983740 TI - Hyperphosphorylation of mutant influenza virus matrix protein, M1, causes its retention in the nucleus. AB - The matrix (M1) protein of influenza virus is a major structural component, involved in regulation of viral ribonucleoprotein transport into and out of the nucleus. Early in infection, M1 is distributed in the nucleus, whereas later, it is localized predominantly in the cytoplasm. Using immunofluorescence microscopy and the influenza virus mutant ts51, we found that at the nonpermissive temperature M1 was retained in the nucleus, even at late times after infection. In contrast, the viral nucleoprotein (NP), after a temporary retention in the nucleus, was distributed in the cytoplasm. Therefore, mutant M1 supported the release of the viral ribonucleoproteins from the nucleus, but not the formation of infectious virions. The point mutation in the ts51 M1 gene was predicted to encode an additional phosphorylation site. We observed a substantial increase in the incorporation of 32Pi into M1 at the nonpermissive temperature. The critical role of this phosphorylation site was demonstrated by using H89, a protein kinase inhibitor; it inhibited the expression of the mutant phenotype, as judged by M1 distribution in the cell. Immunofluorescence analysis of ts51-infected cells after treatment with H89 showed a wild-type phenotype. In summary, the data indicated that the ts51 M1 protein was hyperphosphorylated at the nonpermissive temperature and that this phosphorylation was responsible for its aberrant nuclear retention. PMID- 7983742 TI - Characterization of recombinant murine leukemia virus integrase. AB - Retroviral integration involves two DNA substrates that play different roles. The viral DNA substrate is recognized by virtue of specific nucleotide sequences near the end of a double-stranded DNA molecule. The target DNA substrate is recognized at internal sites with little sequence preference; nucleosomal DNA appears to be preferred for this role. Despite this apparent asymmetry in the sequence, structure, and roles of the DNA substrates in the integration reaction, the existence of distinct binding sites for viral and target DNA substrates has been controversial. In this report, we describe the expression in Escherichia coli and purification of Moloney murine leukemia virus integrase as a fusion protein with glutathione S-transferase, characterization of its activity by using several model DNA substrates, and the initial kinetic characterization of its interactions with a model viral DNA substrate. We provide evidence for functionally and kinetically distinct binding sites for viral and target DNA substrates and describe a cross-linking assay for DNA binding at a site whose specificity is consistent with the target DNA binding site. PMID- 7983743 TI - The 6-kilodalton membrane protein of Semliki Forest virus is involved in the budding process. AB - Alphavirus genomes encode a small hydrophobic protein of 6 kDa (the 6K protein) that is expressed as part of a large polyprotein containing the sequences of the two virus transmembranal glycoproteins which form the spikes of the infectious particle. Although made in amounts equivalent to those of the glycoproteins, very little of the 6K protein is found in secreted infectious virions. The role of this protein in virus replication and structure has been studied by use of a variety of mutationally altered forms of 6K, which yield phenotypically distinct viruses. A complete deletion of the gene encoding the 6K protein (delta 6K) of Semliki Forest Virus (SFV) has been constructed from an SFV infectious cDNA and the transcribed RNA-produced progeny virus that closely resembled the normal virus (P. Liljestrom, S. Lusa, D. Huylebroeck, and H. Garoff, J. Virol. 65:4107 4113, 1991). Further studies of this mutant have now been performed, and they show that growth of delta 6K has a strong dependency on its host cell, varying from 2 to 50% of the rate of formation of the wild-type SFV. Mammalian cells are much more defective than insect and avian cells in replication of the delta 6K mutant. This mutant is not defective in formation and transport of the glycoproteins or in production of nucleocapsids, which accumulate at the plasma cell membrane in infected BHK cells. The major defect, thus, is in the final assembly and budding of new virus. In BHK cells infected with the delta 6K strain, a relatively large fraction of the total infectious virus formed can be recovered by osmotic lysis of exhaustively washed cells. Infectious SFV totally lacking 6K is identical to wild-type SFV in the early stages of virus replication, i.e., binding and uptake. The particles themselves are more thermolabile than those of wild-type SFV, suggesting that the 6K protein may be a part of the structure of wild-type virus or that the slower budding leads to an altered configuration of the trimeric spikes. These data support other studies that implicate the 6K protein as an important but nonessential component in the assembly and budding of the alphavirus particle, perhaps by affecting the packing of the glycoproteins and their interactions with membrane lipid. PMID- 7983741 TI - Long terminal repeat enhancer core sequences in proviruses adjacent to c-myc in T cell lymphomas induced by a murine retrovirus. AB - The transcriptional enhancer in the long terminal repeat (LTR) of the T lymphomagenic retrovirus SL3-3 differs from that of the nonleukemogenic virus Akv at several sites, including a single base pair difference in an element termed the enhancer core. Mutation of this T-A base pair to the C-G C-G sequence found in Akv significantly attenuated the leukemogenicity of SL3-3. Thus, this difference is important for viral leukemogenicity. Since Akv is an endogenous virus, this suggests that the C-G in its core is an adaptation to being minimally pathogenic. Most tumors that occurred in mice inoculated with the mutant virus, called SAA, contained proviruses with reversion or potential suppressor mutations in the enhancer core. We also found that the 72-bp tandem repeats constituting the viral enhancer could vary in number. Most tumors contained mixtures of proviruses with various numbers of 72-bp units, usually between one and four. Variation in repeat number was most likely due to recombination events involving template misalignment during viral replication. Thus, two processes during viral replication, misincorporation and recombination, combined to alter LTR enhancer structure and generate more pathogenic variants from the mutant virus. In SAA induced tumors, enhancers of proviruses adjacent to c-myc had the largest number of core reversion or suppressor mutations of all of the viral enhancers in those tumors. This observation was consistent with the hypothesis that one function of the LTR enhancers in leukemogenesis is to activate proto-oncogenes such as c-myc. PMID- 7983744 TI - Evaluation of colocalization interactions between the IE110, IE175, and IE63 transactivator proteins of herpes simplex virus within subcellular punctate structures. AB - A number of previous studies have implied that three herpes simplex virus-encoded nuclear transactivator proteins, IE175 (ICP4), IE110 (ICP0), and IE63 (ICP27), may cooperate in transcriptional and posttranscriptional stimulation of viral gene expression. Using double-label immunofluorescence assays (IFA) in transient expression assays, we have examined the intracellular localization of these three proteins in DNA-transfected cells. The IE110 protein on its own forms spherical punctate domains within the nucleus, whereas the IE175 and IE63 proteins alone give uniform and speckled diffuse patterns, respectively. In infected cells, the IE110 punctate granules have been shown to correspond to novel preexisting subnuclear structures referred to as ND10 domains or PODs that contain a variety of cellular proteins, including SP100 and the PML proto-oncogene product. Cotransfection experiments with wild-type nuclear forms of both IE175 and IE110 provided direct evidence for partial redistribution of IE175 into the same punctate granules that contained IE110. Surprisingly, nuclear forms of IE110 were found to move a cytoplasmic form of IE175 into nuclear punctate structures, and a cytoplasmic form of IE110 was able to retain nuclear forms of IE175 in cytoplasmic punctate structures. Therefore, the punctate characteristic of IE110 appeared to both dominate the interactions and override the normal nuclear localization signals. The domains responsible for the interaction mapped to between codons 518 and 768 in 1E110 and to between codons 835 and 1029 in IE175. Importantly, a truncated nuclear form of the 1,298-amino-acid IE175 protein, which lacked the C-terminal domain beyond codon 834, was found to be excluded from the IE110 punctate granules. Cotransfection of nuclear or cytoplasmic IE110 with a truncated nuclear form of IE63 also led to partial redistribution of IE63 into either nuclear or cytoplasmic punctate granules containing IE110. Both the IE63-IE110 and IE175-IE110 colocalization interactions were demonstrated in Vero cells but not in 293 cells. Consequently, they differ from IE110 self interactions, which correlate with in vitro dimerization and occur efficiently in both cell types. These interactions may help to explain the altered promoter target specificity and synergism observed when IE175 is cotransfected with IE110 in transactivation studies. PMID- 7983745 TI - Intracellular localization of the herpes simplex virus type 1 major transcriptional regulatory protein, ICP4, is affected by ICP27. AB - Infected-cell protein 4 (ICP4) is the major transcriptional activator of herpes simplex virus (HSV) gene expression during productive infection. ICP0 has broad transactivating activity for all classes of HSV genes as well as cellular genes and genes of heterologous viruses. Together, the transactivating activities of ICP4 and ICP0 are synergistic. ICP27, which alone does not exhibit major transregulatory activity, is able to differentially activate and repress viral gene expression induced by ICP4 and ICP0. Thus, ICP27 plays a modulatory role in viral gene expression. In order to explore the functional relationships among ICP4, ICP0, and ICP27 in the regulation of viral gene expression, we have used indirect immunofluorescence to examine the intracellular localization of ICP4 in cells infected with wild-type virus or with mutant viruses that did not express functional forms of ICP0 or ICP27. Although ICP4 localized to both the nuclei and cytoplasm of cells infected with either the wild-type virus or an ICP0 null mutant virus, this protein was present exclusively in the nuclei of cells infected with an ICP27 null mutant virus, suggesting that ICP27 is able to inhibit the nuclear localization of ICP4 during virus infection. Transient expression assays with pairs of plasmids that express wild-type forms of ICP4 and ICP0 or of ICP4 and ICP27 demonstrated that ICP27 has a significant inhibitory effect on the nuclear localization of ICP4, confirming the observations made with the mutant-virus-infected cells. By using a plasmid expressing wild-type ICP4 and a series of ICP27 mutant plasmids in transient expression assays, the C-terminal half of ICP27 was shown to be required for its inhibitory effect on the nuclear localization of ICP4. In similar studies using a series of ICP4 mutant plasmids, the region of ICP4 responsive to wild-type ICP27 was mapped to the C-terminal portion of the molecule between amino acid residues 820 and 1029. The level of expression of ICP27 was shown to have a significant effect on the intracellular localization of ICP4 in transient assays. These findings are consistent with previous studies in which ICP27 was shown to have an inhibitory effect on the nuclear localization of ICP0 (Z. Zhu, W. Cai, and P. A. Schaffer J. Virol. 68:3027-3040, 1994). Thus, ICP27 has a significant inhibitory effect on the ability of the two major HSV type 1 (HSV-1) regulatory proteins to localize to the nucleus. Collectively, these findings indicate that cooperative regulation of HSV-1 gene expression may well involve intracellular compartmental constraints. PMID- 7983746 TI - Human immunodeficiency virus Tat induces functional unresponsiveness in T cells. AB - Soluble proteins of the human immunodeficiency virus (HIV) might play a significant role in the pathogenesis of HIV infection. The addition of synthetic Tat peptides, but not that of the recombinant Nef or Vif protein, inhibited proliferative responses of CD4+ tetanus antigen-specific, exogenous interleukin-2 (IL-2)-independent T-cell clones in a dose-dependent manner. In addition, Tat peptides inhibited the anti-CD3 monoclonal antibody-induced proliferative responses of both purified CD4+ and CD8+ T cells. Tat did not affect proliferative responses induced by phorbol myristate acetate plus ionomycin. The Tat peptides at the concentrations used (0.1 to 3 micrograms/ml) did not affect the viability of the cells as determined by trypan blue exclusion. Treatment of Tat peptides with polyclonal Tat antibodies abrogated the inhibitory effect of Tat. Soluble Tat proteins secreted by HeLa cells transfected with the tat gene also inhibited antigen-induced proliferation of the T-cell clones. Tat inhibited the anti-CD3 monoclonal antibody-induced IL-2 mRNA expression and IL-2 secretion but did not affect IL-2 receptor alpha-chain mRNA or protein expression on peripheral blood T cells. Finally, treatment of T-cell clones with the Tat peptide did not affect the antigen-induced increase in intracellular calcium, hydrolysis of phosphatidyl inositol to inositol trisphosphate, or translocation of protein kinase C from the cytosol to the membrane. These studies demonstrate that the mechanism of the Tat-mediated inhibition of T-cell functions involves a phospholipase C gamma 1-independent pathway. PMID- 7983747 TI - Congo red prolongs the incubation period in scrapie-infected hamsters. AB - In scrapie-infected cells, Congo red inhibits both the replication of the infectious agent and accumulation of the protease-resistant form of PrP (PrP res). In this report, we show that Congo red prolongs the incubation periods of hamsters experimentally infected with two different strains of scrapie. PMID- 7983748 TI - Isolation of the measles virus hemagglutinin protein in a soluble form by protease digestion. AB - The hemagglutinin (H) glycoprotein was isolated in a soluble form by digesting measles virus particles with an endoproteinase, Asp-N (from a Pseudomonas fragi mutant). Digestion of H with Asp-N brought about glycopeptides in three different forms, depending on the cleaving site: AHD, which has an M(r) of 66,000 as determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and which formed a disulfide-linked homodimer with an M(r) of 132,000, and two monomeric digestion products, AHM-1 (with an M(r) of 64,000) and AHM-2 (with an M(r) of 58,000). The susceptibility of the H glycoprotein to the protease depended on the enzyme concentration. AHD was readily formed at a low concentration of Asp-N, while AHM-1 and AHM-2 required higher and even higher protease concentrations, respectively. All of the cleavage products reacted with monoclonal antibodies to various epitopes of the H protein; however, only AHD showed a significant hemagglutinin activity on African green monkey erythrocytes. The hemagglutinin activities of AHM-1 and AHM-2 were restored after a monoclonal antibody lacking the hemagglutination-inhibiting activity was added to the reaction mixture. AHDs purified by size-exclusion high-pressure liquid chromatography had two associating forms; one had an M(r) higher than and the other an M(r) as high as that of a tetramer. The former was associated noncovalently in addition to having two intermolecular disulfide bonds, and the latter was associated covalently with a single intermolecular disulfide bond and was also duplicated through a noncovalent association. In addition, both AHM-1 and AHM-2, having no intermolecular disulfide bond, were in a dimer form. These results suggest that AHM-1 and AHM-2 are monovalent in the hemagglutinin activity, while AHDs are divalent. Comparative analyses of the N termini of these soluble glycopeptides with the sequence of H suggested that the cysteine residue at position 139 was responsible for the intermolecular disulfide bonding between the monomeric H glycoproteins. The cysteine at position 154 was also suggested to participate in the forming of the intermolecular disulfide bond. PMID- 7983749 TI - Equal levels of gp120 retention and neutralization resistance of phenotypically distinct primary human immunodeficiency virus type 1 variants upon soluble CD4 treatment. AB - Human immunodeficiency virus type 1 (HIV-1) variants passaged in T-cell lines, often called laboratory isolates, are potently neutralized by soluble CD4 (sCD4), whereas primary HIV-1 variants are highly resistant to sCD4 neutralization. Previously, it was demonstrated that the domain from V1 to V3 of the HIV-1 gp120 molecule contains one of the major determinants of sCD4 neutralization sensitivity, and the same region has also been implicated as influencing syncytium-inducing (SI) capacity and T-cell-line tropism. To determine possible differences in sCD4 neutralization sensitivity between phenotypically distinct primary HIV-1 variants, a panel of non-syncytium-inducing (NSI) and SI HIV-1 variants was studied. Primary NSI and SI HIV-1 variants appeared to be equally resistant to sCD4 neutralization. Consistent with this observation, sCD4 did not induce gp120 shedding from either primary NSI or SI HIV-1 variants at 37 degrees C. Thus, it is not the potential of certain primary HIV-1 variants to infect T cell lines but rather their adaptation to T-cell lines that is reflected in specific properties of the viral envelope which influence sCD4 neutralization sensitivity. PMID- 7983750 TI - Human immunodeficiency virus type 1 Nef induces accumulation of CD4 in early endosomes. AB - We have studied the fate of CD4 in CEM T cells expressing a human immunodeficiency virus type 1 HIV-1 Nef protein. Nef triggered a rapid endocytosis and a degradation of CD4, while most of the p56lck was upheld at the cell membrane. In the presence of Nef, CD4 accumulated in acidic intracellular vesicles that were not stained by antibodies against rab6, a marker of the Golgi apparatus complex. Detection of transferrin in CD4-containing vesicles showed that CD4 was trapped in early endosomes, without significant accumulation of CD4 in late endocytic compartments. Internalization pathways taken by CD4 in Nef+ cells may therefore be different from those observed after treatment with phorbol esters. PMID- 7983751 TI - The dual-function hamster receptor for amphotropic murine leukemia virus (MuLV), 10A1 MuLV, and gibbon ape leukemia virus is a phosphate symporter. AB - Previously, we showed that the amphotropic receptor homolog in hamster cells functions as a receptor not only for amphotropic murine leukemia viruses and 10A1 murine leukemia virus but also for gibbon ape leukemia virus (C.A. Wilson, K. B. Farrell, and M. V. Eiden, J. Virol. 68:7697-7703, 1994). Here, we demonstrate that this receptor functions as a sodium-dependent Pi transporter and that Na-Pi uptake can be specifically blocked following infection with either amphotropic murine leukemia virus, 10A1 murine leukemia virus, or gibbon ape leukemia virus. PMID- 7983752 TI - The highly conserved aspartic acid residue between hypervariable regions 1 and 2 of human immunodeficiency virus type 1 gp120 is important for early stages of virus replication. AB - Between hypervariable regions V1 and V2 of human immunodeficiency virus type 1 (HIV-1) gp120 lies a cluster of relatively conserved residues. The contribution of nine charged residues in this region to virus infectivity was evaluated by single-amino-acid substitutions in an infectious provirus clone. Three of the HIV 1 mutants studied had slower growth kinetics than the wild-type virus. The delay was most pronounced in a mutant with an alanine substituted for an aspartic acid residue at position 180. This aspartic acid is conserved by all HIV-1 isolates with known nucleotide sequences. Substitutions with three other residues at this position, including a negatively charged glutamic acid, all affected virus infectivity. The defect identified in these mutants suggests that this aspartic acid residue is involved in the early stages of HIV-1 replication. PMID- 7983755 TI - Functional analysis of the two alternative translation initiation sites of foot and-mouth disease virus. AB - The effect of deletion of each of the two authentic polyprotein translation initiation sites of foot-and-mouth disease virus on viral protein synthesis and replication was analyzed. Deletion of either the first or the second initiation site led to the expression of only one form of the leader protein, L or L', respectively, but in vitro processing of the viral polyprotein and cleavage of eIF-4 gamma were not affected by either deletion. Whereas RNA in which the first translation initiation site had been deleted led to the production of viruses in transfected BHK cells, deletion of the second translation initiation site abolished virus replication. PMID- 7983753 TI - Mouse hepatitis virus receptor activities of an MHVR/mph chimera and MHVR mutants lacking N-linked glycosylation of the N-terminal domain. AB - Mouse hepatitis virus binds to the N-terminal domain of its receptor, MHVR, a murine biliary glycoprotein with four immunoglobulin-like domains (G.S. Dveksler, M. N. Pensiero, C. W. Dieffenbach, C. B. Cardellichio, A.A. Basile, P.E. Elia, and K. V. Holmes, Proc. Natl. Acad. Sci. USA 90:1716-1720, 1993). A recombinant protein with only the anchored N-terminal domain was not a functional receptor, but a recombinant protein with the N-terminal domain of MHVR linked to the second and third immunoglobulin-like domains and anchor from the mouse poliovirus receptor homolog, mph, was a functional receptor for mouse hepatitis virus. The native four-domain MHVR has 16 potential N-linked glycosylation sites, including three on the N-terminal domain. Recombinant proteins lacking each one of these three sites or all three of them were functional receptors. Thus, glycosylation of the N-terminal domain is not required, but a glycoprotein longer than the N terminal domain is required for virus receptor activity. PMID- 7983756 TI - Constitutive phosphorylation and turnover of I kappa B alpha in human T-cell leukemia virus type I-infected and Tax-expressing T cells. AB - Human T-cell leukemia virus type I (HTLV-I) encodes a strong transcriptional activator, Tax, that stimulates transcription indirectly through the viral long terminal repeat and also activates a number of cellular genes via association with host transcription factors. The NF-kappa B/Rel pathway is a target for Tax trans-activation, and Tax has been correlated with increased NF-kappa B-binding activity and NF-kappa B-dependent gene expression in HTLV-I-infected cells. In this study we demonstrate that constitutive phosphorylation and increased turnover of the regulatory I kappa B alpha protein in HTLV-I-infected MT-2 and C8166 cells and Tax-expressing 19D cells contribute to constitutive NF-kappa B binding activity, which consists primarily of c-Rel, p52(NFKB2), and p50(NFKB1). I kappa B alpha mRNA expression is also increased 7- to 20-fold in these cells, although the steady-state level of I kappa B alpha protein is reduced in HTLV-I infected and Tax-expressing T cells. These results indicate that the viral Tax protein, by indirectly mediating phosphorylation of I kappa B, may target I kappa B alpha for rapid degradation, thus leading to constitutive NF-kappa B activity. PMID- 7983754 TI - Retinoid X receptor alpha transactivates the hepatitis B virus enhancer 1 element by forming a heterodimeric complex with the peroxisome proliferator-activated receptor. AB - The hepatitis B virus enhancer 1 contains a retinoic acid responsive element (RARE). We have previously demonstrated that retinoid X receptor alpha (RXR alpha) transactivates enhancer 1 by binding to the RARE. The present study has revealed that a heterodimeric complex composed of RXR alpha and peroxisome proliferator-activated receptor (PPAR) interacts with the hepatitis B virus RARE. Transient transfection studies, in conjunction with in vitro DNA binding data, support the hypothesis that the RXR alpha-PPAR heterodimer transactivates enhancer 1. PMID- 7983757 TI - Amphotericin B derivative blocks human immunodeficiency virus type 1 entry after CD4 binding: effect on virus-cell fusion but not on cell-cell fusion. AB - The antiviral effect of MS8209, an amphotericin B derivative, was studied in CD4+ cells transfected with a lacZ gene inducible upon human immunodeficiency virus type 1 (HIV-1) infection. MS8209 was shown to block virus entry after receptor binding and probably before virus-cell membrane fusion, but it had no effect on syncytium formation, although both processes are mediated by HIV-1 envelope proteins and CD4. PMID- 7983758 TI - Transcription factor Oct1 binds to the AT-rich segment of the simian virus 40 replication origin. AB - A cellular protein that binds to the AT-rich late segment of the simian virus 40 (SV40) origin of replication has been identified as transcription factor Oct1. This conclusion is based on the following observations: the late origin binding protein has a molecular mass of about 100 kDa, like factor Oct1, and shares other biochemical properties with Oct1; its binding to the origin is inhibited by antibodies directed against the POU domain of factor Oct1; the isolated POU domain of Oct1 specifically binds to the SV40 late origin region. Thus, the SV40 genome contains binding sites for transcription factor Oct1 in the origin of replication in addition to the previously characterized octamer sites in the viral promoter enhancer. Oct1, bound to the viral origin, negatively affects the DNA unwinding reaction catalyzed by the viral replication initiator T antigen, suggesting that Oct1 may have a role in the regulation of viral replication. PMID- 7983759 TI - Expression of the human immunodeficiency virus type 1 (HIV-1) nef gene during HIV 1 production increases progeny particle infectivity independently of gp160 or viral entry. AB - The nef gene product of human immunodeficiency virus type 1 (HIV-1) promotes more rapid kinetics of viral replication in primary peripheral blood mononuclear cells. We have previously shown that these enhancing effects of Nef on HIV-1 replication reflect an increase in viral infectivity detectable both in limiting dilution assays and through a single-cycle infection of the HeLa-CD4-long terminal repeat-beta-galactosidase indicator cell line. We now demonstrate that nef-defective HIV-1 can be rescued to near wild-type levels of infectivity by coexpressing Nef in trans in the cell line producing the virus. This observation indicates that HIV-1 virions produced in the presence of Nef are intrinsically different. However, we show that the major viral structural proteins are quantitatively similar in purified viral preparations. We also demonstrate the functional equivalence of the gp120-gp41 envelope glycoprotein complexes of Nef+ and Nef- HIV-1 through an assay for viral entry. Finally, we show that env defective Nef+ HIV-1 pseudotyped with an amphotropic envelope is also more infectious than similarly pseudotyped Nef- HIV-1. Thus, the production of HIV-1 in the presence of Nef results in viral particles that are more infectious, and this increased infectivity is manifested at a stage after viral entry but prior to or coincident with HIV-1 gene expression. PMID- 7983761 TI - Intragenomic linear amplification of human herpesvirus 6B oriLyt suggests acquisition of oriLyt by transposition. AB - We identified some passage lineages of human herpesvirus 6 variant B (HHV-6B) strain Z29 that contain as many as 12 tandem copies of a genomic segment that corresponds almost precisely to a previously identified minimal efficient origin of lytic replication (oriLyt). Analysis of nucleotide sequences in the vicinity of the amplified segment suggests that the amplification occurred as a two-step process, with the first step being a rare sequence duplication mediated through directly repeated sequences located near the termini of the amplified segment and the second step occurring via homologous recombination through the duplicated sequence. These results demonstrate that oriLyt has been amplified in some virus stocks and indicate that (i) origin amplification confers a growth advantage on the virus in cell culture and (ii) laboratory-passaged HHV-6B genomes can accommodate additional nucleotide sequences and thus may be useful gene transfer vectors. The structures of the amplified segment and its adjacent sequences together suggest that HHV-6B or a progenitor virus acquired oriLyt by transposition from an unknown source. PMID- 7983762 TI - Identification and characterization of a temperature-sensitive mutant of human immunodeficiency virus type 1 by alanine scanning mutagenesis of the integrase gene. AB - We have created a temperature-sensitive (ts) mutant of human immunodeficiency virus type 1, using the technique of charge-cluster-to-alanine scanning mutagenesis to introduce specific changes into the integrase coding region. In the ts mutant virus, the lysine at amino acid 136 and the glutamic acid at amino acid 138 of integrase have been replaced with alanines (K136A/E138A). When K136A/E138A is synthesized at 35 degrees C, it replicates to a similar degree as wild-type virus during infection of CEM cells at 35 degrees C on the basis of syncytium formation, levels of core antigen, and reverse transcriptase activity. However, during infection at the nonpermissive temperature of 39.5 degrees C, K136A/E138A is capable of only one round of integration. Mutant virions formed at 39.5 degrees C do not integrate but are indistinguishable from wild-type virions when scored for activity of reverse transcriptase and correct expression and processing of Gag and Pol proteins. We demonstrate that the defect responsible for the ts phenotype of K136A/E138A is localized to a step after proviral formation and integrase protein synthesis but prior to particle maturation. It is the temperature at which the K136A/E138A virion is synthesized, not the temperature at which infection occurs, which determines the ability of the virus to integrate. PMID- 7983760 TI - The Epstein-Barr virus nuclear protein 2 acidic domain can interact with TFIIB, TAF40, and RPA70 but not with TATA-binding protein. AB - The Epstein-Barr virus nuclear antigen 2 (EBNA-2) acidic domain is essential for B-lymphocyte growth transformation and can activate transcription when brought to a promoter by a sequence-specific DNA-binding domain. We now show that the EBNA-2 acidic domain has slightly less activity than the proteotypic acidic transactivator VP16 in depleting nuclear extracts of basal transcription activity. Like VP16, EBNA-2 associates with TFIIB, TAF40, and RPA70. However, EBNA-2 has much less avidity for TATA-binding protein. A Trp-to-Thr mutation within the acidic domain abolishes EBNA-2 transactivating activity and greatly compromises the association with TFIIB, TAF40, and RPA70, establishing a genetic linkage between transactivating activity and these associations. PMID- 7983763 TI - Mutational analysis of the murine AIDS-defective viral genome reveals a high reversion rate in vivo and a requirement for an intact Pr60gag protein for efficient induction of disease. AB - Pr60gag appears to be the only protein encoded by the murine AIDS (MAIDS) defective virus. To study the role of Pr60gag or some other sequences of the viral genome in the pathogenicity of the virus, we have generated mutants of the defective viral genome. These mutant defective viruses, prepared as helper-free stocks, were inoculated into susceptible C57BL/6 mice. Mutant Du5H-A virus, which had a stop codon within gag MA(p15), did not induce target cell proliferation or MAIDS. Mutants Du5H-B and -C encoded truncated Pr60gag proteins containing, respectively, MA(p15)-p12 or MA(p15)-p12 and part of CA(p30). These mutants showed a very limited capacity to induce early cell expansion and were poorly pathogenic. Only recombinant (revertant) viruses were recovered from organs of diseased mice inoculated with these two mutants. Mutant Du5H-D was generated by deleting 1.4 kbp of the 3'-end sequences, outside the gag coding region. The levels of RNA and proteins made by this mutant were low. This mutant also reverting frequently but was nevertheless able to induce MAIDS at a low efficiency without reverting. Our results indicate that the Pr60gag protein is necessary and sufficient to induce MAIDS. These data also suggest that the Pr60gag protein needs to be relatively intact to be fully pathogenic. In addition, our study shows a very high reversion rate of some mutants and emphasizes the need to check for the presence of revertant (recombinant) viruses in diseased organs when working with mutants of the MAIDS-defective virus. PMID- 7983764 TI - Immunization with nonstructural proteins E1 and E2 of cottontail rabbit papillomavirus stimulates regression of virus-induced papillomas. AB - Cottontail rabbit papillomavirus is the major animal model for cancer-associated papillomaviruses. Here we show that vaccination with the nonstructural proteins E1 and E2 induces the regression of virus-induced papillomas and that vaccination is equally effective when proteins are given with and without adjuvant. There was no correlation between antibody levels and regression, suggesting that tumor regression may be due to a cell-mediated response. PMID- 7983765 TI - Major histocompatibility complex class I-restricted cytotoxic T-lymphocyte responses in horses infected with equine herpesvirus 1. AB - An experimental system that permits sensitive and reproducible detection of equine herpesvirus 1 (EHV-1)-specific cytotoxic T-lymphocyte (CTL) activity in the horse was developed. Peripheral blood mononuclear cells (PBMC) collected from immune horses were restimulated in vitro by culture with live EHV-1. Cytotoxic activity against virus-infected, pokeweed mitogen-stimulated lymphoblast targets was assessed in a 4-h 51Cr release assay. The optimal conditions for in vitro stimulation of equine memory CTLs and for preparation of EHV-1-infected target cells expressing viral antigens were systematically identified by individually testing the effects of variations in responder cell concentration, culture medium composition, serum type, incubation time, antigen form, and exogenous mediator content. By using this optimized system for generation and assay of equine CTLs, the development of EHV-1-specific cytotoxic responses in 12 horses was evaluated after experimental viral infection. CTLs with the capacity for killing EHV-1 infected target cells were detected in equine PBMC as early as 1 week postinfection, reached maximal levels by 2 to 3 weeks, and remained detectable for a year after infection. Equine effector cells mediating lysis of EHV-1 infected targets were predominantly CD8+ T lymphocytes, and the cytotoxicity was specific for virus and restricted by major histocompatibility complex class I molecules. The results define a reliable and convenient experimental system for generation and assay of EHV-1 CTLs which can now be used for more-detailed characterization of the equine CTL response to infection by this herpesvirus pathogen. PMID- 7983767 TI - Identification of multirestricted immunodominant regions recognized by cytolytic T lymphocytes in the human immunodeficiency virus type 1 Nef protein. PMID- 7983766 TI - Disulfide bonds between two envelope proteins of lactate dehydrogenase-elevating virus are essential for viral infectivity. AB - Disulfide bonds were found to link the nonglycosylated envelope protein VP-2/M (19 kDa), encoded by open reading frame 6, and the major envelope glycoprotein VP 3 (25 to 42 kDa), encoded by open reading frame 5, of lactate dehydrogenase elevating virus (LDV). The two proteins comigrated in a complex of 45 to 55 kDa when the virion proteins were electrophoresed under nonreducing conditions but dissociated under reducing conditions. Furthermore, VP-2/M was quantitatively precipitated along with VP-3 in this complex by three neutralizing monoclonal antibodies to VP-3. The infectivity of LDV was rapidly and irreversibly lost during incubation with 5 to 10 mM dithiothreitol (> 99% in 6 h at room temperature), which is known to reduce disulfide bonds. LDV inactivation correlated with dissociation of VP-2/M and VP-3. The results suggest that disulfide bonds between VP-2/M and VP-3 are important for LDV infectivity. Hydrophobic moment analyses of the predicted proteins suggest that VP-2/M and VP 3 both possess three adjacent transmembrane segments and only very short ectodomains (10 and 32 amino acids, respectively) with one and two cysteines, respectively. Inactivation of LDV by dithiothreitol and dissociation of the two envelope proteins were not associated with alterations in LDV's density or sedimentation coefficient. PMID- 7983768 TI - Direct interactions between autoantigen La and human immunodeficiency virus leader RNA. PMID- 7983769 TI - Inhibition of dengue virus by novel, modified antisense oligonucleotides. AB - Five different target regions along the length of the dengue virus type 2 genome were compared for inhibition of the virus following intracellular injection of the cognate antisense oligonucleotides and their analogs. Unmodified phosphodiester oligonucleotides as well as the corresponding phosphorothioate oligonucleotides were ineffective in bringing about a significant inhibition of the virus. Novel modified phosphorothioate oligonucleotides in which the C-5 atoms of uridines and cytidines were replaced by propynyl groups caused a significant inhibition of the virus. Antisense oligonucleotide directed against the target region near the translation initiation site of dengue virus RNA was the most effective, followed by antisense oligonucleotide directed against a target in the 3' untranslated region of the virus RNA. It is suggested that the inhibitory effect of these novel modified oligonucleotides is due to their increased affinity for the target sequences and that they probably function via an RNase H cleavage of the oligonucleotide:RNA heteroduplex. PMID- 7983770 TI - Unique insertion sequence and pattern of CD4 expression in variants selected with immunotoxins from human immunodeficiency virus type 1-infected T cells. AB - To study the variability of human immunodeficiency virus type 1 (HIV-1), we used immunotoxins to select for variants within a population of H9 cells persistently infected with a molecular clone of HIV-1 designated NL4-3. Chimeric immunotoxin CD4-PE40 (a chimeric fusion protein consisting of the amino-terminal two domains of CD4 and the carboxy-terminal domains of Pseudomonas exotoxin A) was used to select for cells lacking cell surface expression of HIV Env (envelope proteins gp160, gp120, and gp41). The cells described here (A1, A7, C9, and E9) fail to express HIV proteins because they have markedly diminished transcription of the integrated provirus (A1, A7, and E9) or no HIV provirus (C9). Analysis demonstrated that two different cloned variants, A1 and E9, contain the complementary sequence of tRNA(3Lys) (45 bp) inserted 3' to the primer-binding site, following by a 169-bp deletion through the start of the gag gene. No HIV mRNA was detected by Northern (RNA) blotting, but PCR demonstrated the presence of the viral message. These variants were found very infrequently in the unselected H9/NL4-3 cell population, and they contained proviruses distinct from that found in the dominant population. In addition, all of these variants had similar patterns of CD4 surface expression that allowed them to escape reinfection within the tissue culture. The data are discussed with regard to mechanisms and errors of HIV reverse transcription, as well as the evolution of mutants within a population of persistently infected cells. PMID- 7983772 TI - [The molecular mechanism of insulin biosynthesis and mutant insulin gene syndrome]. AB - The biosynthetic process of insulin in pancreatic beta cells consists of many steps including transcription of insulin gene to mRNA, translation of mRNA to preproinsulin, production of proinsulin by cleavage of signal peptide, and conversion of proinsulin to insulin and C-peptide. This process also includes intra-cellular trafficking (nucleus, cytoplasm, endoplasmic reticulum, Golgi apparatus, secretary granule, and extra-cellular secretion). The factors concerning and regulating these steps are discussed, although some of these have not been fully understood. The possible influences of insulin gene mutations (mutant insulin gene syndrome) to these steps are also discussed. Understanding of the molecular mechanism of insulin biosynthesis might be usefull to explain the defective insulin production of NIDDM. PMID- 7983771 TI - Characterization of nef sequences in long-term survivors of human immunodeficiency virus type 1 infection. AB - Studies with the simian immunodeficiency virus have shown that nef deletion results in a low level of viremia and a lack of disease progression in monkeys. Given the similarity of this clinical profile to that observed in long-term survivors of human immunodeficiency virus type 1 (HIV-1) infection, we sought to examine the nef gene in 10 patients who are clinically healthy and immunologically normal despite 12 to 15 years of infection. PCR and DNA sequencing were used to determine nef sequences in peripheral blood mononuclear cells obtained from long-term survivors. We found that there is no gross deletion within nef in the cases studied; most nef sequences (91.1%) obtained from 10 subjects contained a full-length and intact open reading frame. In addition, at the protein level, there were no discernible differences between the Nef consensus sequences derived from long-term survivors and those from patients with AIDS. We therefore conclude that deletion of or gross sequence abnormality within nef is not likely to be a common explanation for the well-being of long-term survivors of HIV-1 infection. Moreover, phylogenetic analysis of nef sequences suggests that HIV-1 strains found in our study subjects do not have a common origin. PMID- 7983773 TI - [Regulation of human insulin gene expression by cAMP]. AB - Various hormones and neurotransmitters as well as glucose are known to increase the cAMP concentration in pancreatic beta cells. To determine the mechanism by which cAMP augments insulin gene expression, we first identified the cAMP response elements (CREs) of the human insulin gene. In DNase I footprint analysis, the bacterially synthesized CRE-binding protein, CRE-BP1, protected four sites: two sites in the region upstream from the insulin core promoter, one site in the first exon, and one site in the first intron. To examine the roles of those four sites, we constructed a series of DNA plasmids in which the wild-type and mutant insulin promoters were linked to the chloramphenicol acetyltranferase (CAT) gene. Studies of the transcriptional activity of these plasmids after transfection into hamster insulinoma cells (HIT) showed that these four sites contributed additively to the cAMP inducibility of the insulin promoter. PMID- 7983774 TI - [Transcription factors for the insulin gene]. AB - Production of insulin is stringently restricted to the beta cells of the endocrine pancreas. The major mechanism directing this specificity operates at the level of transcription. Previous studies have demonstrated that the tissue specificity in the insulin gene expression results from the cell-specific activity of its 5'-flanking enhancer/promoter, which limits the expression of a linked gene to the beta cell in tissue culture and transgenic mouse. Deletion, mutation, DNase I foot-printing, and gel-shift analyses revealed the presence of multiple cis-acting motifs. A set of positive and, possibly, negative trans acting factors that are found in insulin-producing and noninsulin producing cells bind to these cis-acting elements and thus regulate transcription. Included among those are IEB (E-box)-binding IEF-1, a nuclear protein complex which consists of two basic helix-loop-helix proteins, and CT-box (TAAT box)-binding IPF1/STF-1, a homeodomain-containing transcription factor. PMID- 7983776 TI - [Review for clinical molecular genetics of mutant insulin]. AB - Three types of structurally abnormal insulin "Insulin Chicago, Los Angeles and Wakayama" has been identified in 6 families by the recent development of molecular biology. It has been clarified that a point mutation in the coding region of each patient's insulin gene allele give rise to a substitution of one amino acid of each insulin, resulting in reduced biological activities of these insulins. These abnormal insulin have slow metabolic clearance rate which cause typical hyperinsulinemia accompanying normal level of plasma C-peptide. In this paper, we review insulin gene mutations and discuss its participation to the pathogenesis of NIDDM. PMID- 7983775 TI - [Analysis of the gene encoding human PC2, a prohormone processing enzyme]. AB - Prohormone Convertase 2 (PC2) is a specific endoprotease responsible for the processing of proinsulin to insulin. PC2 is expressed in pancreatic islets, pituitary and brain but is very low or absent in most other tissues, such as liver, spleen and kidney. To evaluate the regulated expression of the human PC2 gene we have analyzed its structure and characterized its promoter. The gene spans > 130 kilobase pairs and consists of 12 exons. Comparison with the structure of the gene encoding human furin, revealed a high degree of conservation of exon-intron junctions. The hPC2 gene was localized to chromosome 20, band p11.2. The promoter region of the PC2 gene is very G + C rich and contains six potential Sp1 binding sites but no TATA or CAAT box. Analysis of the level of chrolamphenicol acetyltransferase activity with several deletion mutants identified the region from -1100 to -539 from the translation start site as essential for the PC2 promoter activity. PMID- 7983777 TI - [Etiology and molecular biology of hyperproinsulinemia]. AB - Clinical hyperproinsulinemia occurs not only in familial hyperproinsulinemia, but also in insulinoma, renal failure, and even in non-insulin-dependent diabetes mellitus (NIDDM). The etiology of hyperproinsulinemia is divided into (1) abnormality of pro-insulin molecules, (2) abnormality of pancreatic beta-cells other than proinsulin molecules, (3) retardation of proinsulin clearance. Hyperproinsulinemia is now thought to be both a result of the above-mentioned diseases and a cause of atherosclerosis in patients with NIDDM. Recent developments in molecular biology have deepened our knowledge of the biosynthesis and role of proinsulin, especially the prohormone sorting mechanism into secretory granules in pancreatic beta-cells. PMID- 7983778 TI - [Organization of the human GLUT2 gene and regulation of the GLUT2 gene expression]. AB - The high Km glucose transporter, termed GLUT2, is expressed in pancreatic beta cells and hepatocytes in a tissue specific manner. Previous studies revealed that higher glucose levels cause increased GLUT2 gene expression in beta-cells and hepatocytes and that 11 exons of human GLUT2 gene are spanning around 30 kilobases in q26.1-->q26.3 region of was has been chromosome 3. While the putative transcriptional start site has been reported, we made a series of deletion analyses of the human GLUT2 gene promoter region and showed that the sequences located downstream of the putative transcriptional start site are essential for transcription not only in a hamster beta-cell line but also in primary cultured rat hepatocytes. PMID- 7983779 TI - [The detection of GLUT2 gene mutation by polymerase-chain reaction single stranded conformation polymorphism (PCR-SSCP) method]. AB - The polymerase chain reaction-single stranded conformation Polymorphism (PCR SSCP) procedure was applied to examine whether the mutation in the liver/islet glucose transporter (GLUT2) gene could be associated with non-insulin-dependent diabetes mellitus (NIDDM) in Japanese. Samples were processed through 30-40 cycles of 1 min denaturation at 94 degrees C, 1 min annealing at 55-68 degrees C for 1-2 min, extention at 72 degrees C for 1 min, and denaturation at 94 degrees C for 1 min. We identified a silent mutation in codon 479 for PheTTT/TTC. PMID- 7983780 TI - [Human glucokinase gene and analysis of its promoter region]. PMID- 7983781 TI - [Analysis of glukokinase gene by SSCP method]. AB - 1. Peripheral blood was obtained. 2. genomic DNA was purified from leukocytes. 3. Glukokinase gene was amplified by PCR using genori. DNA as a tenple. 4. PCR product was analyzed by SSCP. PMID- 7983782 TI - [Glucokinase gene abnormalities in maturity-onset diabetes of the young (MODY) and late-onset NIDDM]. AB - Glucokinase is a key enzyme of glucose metabolism that phosphorylates glucose to glucose-6-phosphate (G-6-P). This is the first step of glucose metabolism after the uptake of glucose by glucose transporter 2 (GLUT 2). Glucokinase is one of the hexo-kinases and is expressed only in pancreatic beta cells and hepatocytes. Recently it was reported that glucokinase gene is associated with some families with MODY (maturity-onset diabetes of the young). As MODY is a subtype of diabetes which is inherited autosomal dominantly, the correlation of diabetes with glucokinase gene was vigorously studied in many laboratories. The first mutation in exon 7 of the glucokinase gene was reported in 1992. Since the first report of the glucokinase gene mutation in exon 7, a number of mutations and a deletion were reported to be associated with MODY or late-onset NIDDM. But investigations by many groups revealed that glucokinase gene abnormalities are responsible for less than one per cent of NIDDM which is relatively small compared with diabetes with mitochondrial gene alterations. PMID- 7983783 TI - [Molecular mechanism of the K+ATP channel in pancreatic beta-cells]. AB - The ATP-sensitive K+ (K+ATP) channel plays a key role in secretion of insulin in response to glucose-stimulation in pancreatic beta-cells. Inhibition of the channel does not require hydrolysis of ATP and results from a direct binding of ATP4- to the channel. MgADP relieves the channel inhibition by ATP by decreasing affinity of the channel to ATP. We suggest two-sites model regarding channel modulations by these nucleotides; one is the ATP-inhibition site which is bound by ATP4-, and the other the modulation site, which is bound by MgADP and thereby decreases the sensitivity of the channel to ATP. Sulphonylureas-binding sites may be different from these nucleotide-binding sites described above. PMID- 7983784 TI - [The alpha 1 subunit of voltage-dependent calcium channel expressed in pancreatic beta cells]. AB - Calcium channels play an important role in insulin secretion from pancreatic beta cells, in which two different L-type voltage-dependent Ca2+ channels (VDCC), the beta cell/neuron type and the cardiac type are expressed. The former pre-dominant subtype gene (hCa CN4) consists of 49 exons spanning 120 kilo-bases. The promoter region of hCaCN4 is similar to that of housekeeping gene, which is extremely G+C rich and lacks a TATA-like sequence but has three possible binding regions for transcriptional factor Sp1. Changes of calcium channel mRNA in rat pancreatic islets after glucose infusion are introduced. It is important to investigate variations or mutations in the hCaCN4 gene, causing insufficient insulin secretion, leading to NIDDM. PMID- 7983785 TI - [Molecular genetics of mitochondria and diabetes]. AB - The molecular genetics of mitochondria relevant to NIDDM is described, because the mutations in mitochondrial DNA cause diabetes. The non-Mendelian genetics, including maternal inheritance, heteroplasmy, stochastic segregation are characteristic of mitochondrial gene. Since aging causes rapid loss of mitochondrial function, which results in the retardation of insulin secretion via ATP-sensitive K-channel. This loss is not caused by the age-dependent mutation in the mitochondrial DNA, but by a nuclear aging, perhaps accompanied by the shortening of telomere. This was shown by the cybrid experiment. The aged mitochondria in cytoplasts are transferred to immortal rho = cells (cells devoid of mitochondrial DNA) and restored its oxidative and transcriptional activities (J. Biol. Chem. 269:6878, 1994). Thus, the control mechanism of transcription in mitochondria has been analyzed. The genes for mitochondrial transcription factor (mtTF1) an MRP-RNA have been sequenced and their regulatory elements are found (BBRC 194:544, 1993 etc.) The mutations in mitochondrial DNA that cause diabetes have been found, and from the stochastic segregation of the heteroplasmic mutated mitochondrial DNA, we could explain why the MELAS mutation is concentrated in some tissue (J. Neurol. Sci. 120:174, 1993). Although there have been many reports on the mitochondrial mutations found in diabetic patients, we have to be careful on polymorphism (J. Biol. Chem. in press). PMID- 7983786 TI - [A pedigree with maternally transmitted diabetes mellitus, deafness and cardiomyopathy]. AB - A pedigree with maternally transmitted diabetes mellitus, deafness, and cardiomyopathy is described. A A-->G mutation at nucleotide pair 3243 in mitochondrial gene was detected by Apa I digestion of PCR amplified genomic DNA from 3 brothers and their mother. The proband, suffering from CHF, showed unique fine granular pattern of hyperechogenic cardiomyopathy as his brother and their mother did. Although he is recently treated with insulin, he was initially NIDDM treated by sulfonylurea. His urinary CPR excretion decreased gradually to as low as less than 10 micrograms/day in these 3 years. The insulin response to oral glucose was decreased in all other family members with the mutation. It is suggested that the defective insulin secretion exists in this family with the mutation and the progressive decrease in insulin secretion might resulted in IDDM in the proband. PMID- 7983788 TI - [Characterization and expression of the insulin receptor gene and its promoter]. AB - Insulin initiates diverse biological effects by binding to the insulin receptor. The insulin receptor gene is located on the short arm of chromosome 19 and is more than 130 kb in length and contains 22 exons. Two species of mRNAs encoding insulin receptors that differ 12 amino acids in length exist by alternative splicing of the exon 11. The promoter region of the human insulin receptor gene is extremely GC rich and lacks typical TATA and CAAT boxes but contains multiple potential binding sites of Sp1, which are the characteristics of a "housekeeping" gene. Possible regulation of the expression of the insulin receptor gene by hormones such as insulin and dexamethasone and some transcription factors including Sp1 and C/EBP have been shown at the mRNA and transcription levels. PMID- 7983787 TI - [The structure function relationship in the human insulin receptor]. AB - The human insulin receptor gene is composed of 22 exons and spans in excess of 130 kb, on chromosome 19. The basic structure of the insulin receptor is a disulfide-linked tetramer, composed of the alpha subunit (135 kDa), which is extracellular and provides the binding site for insulin, and the beta subunit (95 kDa), contains the transmembrane domain, tyrosine kinase domain and C-terminal domain. Insulin binding to the alpha subunit causes the activation of the receptor tyrosine kinase activity that plays a critical role in mediating insulin signal transduction. Site-directed mutagenesis or the gene analysis of the patients with insulin resistant diabetes mellitus has revealed the structure and functional relationship of the insulin receptor to some extent but further investigations required. PMID- 7983789 TI - [Extreme insulin resistance type A]. AB - Extreme insulin resistance Type A is defined as the syndrome with decreased insulin sensitivity associated with decreased insulin binding to the receptor. The patients usually present with acanthosis nigricans, hirsutism and polycystic ovary. The mechanism for deceased insulin binding includes decreased affinity of insulin receptors, abnormal biosynthesis of the receptor i.e. defect of processing from proreceptor to mature receptor and increased degradation of the proreceptors. The same mutation in the insulin receptor does not always necessarily show the same phenotypes of skin lesion or the same glucose intolerance. PMID- 7983790 TI - [Type C insulin resistance]. AB - Type C insulin resistance in insulin receptor mutations is characterized by normal insulin binding to cultured fibroblasts or EB virus transformed lymphocytes from the patients and decreased insulin receptor kinase activities. However, it is sometimes difficult to classify the state of insulin resistance clearly. The intracellular beta-subunit mutations of insulin receptor which showed decreased kinase activities is reviewed here. Moreover, two cases with typical type C insulin resistance reported previously are also described. One is a case with deletion of the tyrosine kinase domain of the insulin receptor and the other is a Glycine-1008 to Valine mutation. Our studies suggest that the insulin resistance associated with these mutated genes in the kinase domain of insulin receptor were inherited, as an autosomal dominant trait. PMID- 7983791 TI - [Rabson-Mendenhall syndrome]. AB - Rabson-Mendenhall syndrome was initially reported in 1956 by Rabson et al., who described three children with familial hyperplasia of pineal gland and diabetes mellitus. Characteristic features of this syndrome are low birthweight, thickened nails, hirsutism, acanthosis nigricans, dental precosity and dysplasia, polycystic ovary, abdominal proturbance, phallic enlargement and insulin resistant diabetes mellitus. Most patients die of ketoacidosis and intercurrent infection associating with extreme insulin resistance during mid-childhood. This syndrome appears to show autosomal recessive inheritance. Recent reports provide evidence that mutations in the insulin-receptor gene are, at least in pant, the cause of this syndrome, and that recombinant IGF-I (insulin-like growth factor-1) reduces hyperglycemia in patients of this syndrome. PMID- 7983792 TI - [Donohue's syndrome (Leprechaunism)]. AB - The syndrome of leprechaunism is characterized by the elfin-like face, hirsutism, acanthosis nigricans, absence of subcutaneous fat, and intrauterine and neonatal growth retardation. Most of the cases have severe insulin resistance with the mutation of the insulin receptor gene. In some cases, patient had two different mutations of the insulin receptor gene, and showed extremely severe insulin resistance. However, the genetic abnormalities responsible for the patient's phenotype, other than the insulin resistance, have not been found. Further study to define the additional genetic defects will be necessary to understand the abnormalities of this disorder. PMID- 7983793 TI - [HAIR-AN syndrome]. AB - Many clinical observations have suggested that there is a strong relationship between hyperinsulinemia and hyperandrogenism. HAIR-AN syndrome is defined as a constellation of hyperandrogenism (HA), insulin resistance (IR), and acanthosis nigricans (AN). Two major mechanisms could account for this syndrome: (i) hyperinsulinemia induced by insulin resistance causes hyperandrogenism, and (ii) hyperandrogenism causes insulin resistance and hyperinsulinemia. Acanthosis nigricans is considered to be an epiphenomenon caused by hyperinsulinemia. The causes of HAIR-AN syndrome include syndromes of extreme insulin resistance due to mutations in the insulin receptor gene, lipoatrophic diabetes, obesity, some endocrinopathies, and genetic and acquired ovarian hyperandrogenism. PMID- 7983794 TI - [Classification of mutations in the insulin receptor gene]. AB - Mutations in the insulin receptor gene can cause insulin resistance by interfering with a step (s) in the life cycle of the insulin receptor. These steps include biosynthesis, posttranslational modifications and transport to plasma membrane, ligand binding, trans membrane signaling, and endocytosis, recycling and degradation. Mutations are functionally classified into five classes: mutations that decrease the rate of receptor biosynthesis (class I), mutations that impair intracellular transport and post-translational processing (class II), mutations that cause defects in insulin binding (class III), mutations that impair receptor tyrosine kinase activity (class IV), and mutations that accelerate receptor degradation (class V). Examples of insulin receptor gene mutations for each of these five classes are shown. PMID- 7983795 TI - [Characterization of the IRS-1 (insulin receptor substrate-1) gene and its promoter]. AB - IRS-1 (insulin receptor substrate-1) is a major substrate of the insulin receptor. Rat and human IRS-1 cDNAs, and human and mouse IRS-1 genes have been cloned so far. They show high homology in nucleic acids and amino acids levels, which indicate the high conservation of IRS-1 across the species. Interestingly, the entire coding region is contained in the 1st exon in the IRS-1 gene. The promoter of the mouse IRS-1 gene lacks TATA and CAAT boxes but contains 9 potential Spl binding sites, indicating that IRS-1 is a "housekeeping" gene. By deletion analysis, two positively and two negatively regulating fragments are identified in the promoter. In cultured adipocytes, insulin and dexamethasone down regulate IRS-1 expression by different mechanisms. Insulin down regulates at the post-translational level by shortening the protein half life, and dexamethasone down regulates at the post-transcriptional level mainly by shortening the mRNA half life. PMID- 7983796 TI - [Molecular mechanisms of insulin-stimulated glucose uptake and PI3-kinase]. PMID- 7983797 TI - [The role of phosphorylation cascade in insulin action]. AB - Insulin induces a wide variety of growth and metabolic response in many cell types. Insulin initiates its biological effects by activation of tyrosine kinase in the beta-subunit and phosphorylates several proteins, such as insulin receptor substrate-1 (IRS-1), Shc. thereby activating phosphatidyl inositol 3-kinase activity, and ras activity. MAP kinase cascade activated by ras, 70kDaS6 kinase lying downstream of PI3-kinase, and the regulation of glycogen synthase have been discussed. PMID- 7983798 TI - [Heterogeneity in pathogenesis of NIDDM and recent advances in research of diabetogenic genes]. AB - Impaired insulin secretion and/or insulin resistance are the primary defect(s) in the pathogenesis of non-insulin-dependent diabetes mellitus (NIDDM). Both seem to be regulated by the genetic factors in addition to environmental factors. Recent Advances are revealing the molecular mechanism how insulin is secreted in response to glucose and how insulin acts on the target tissues. Several genes including glucokinase and mitochondria have been shown to be responsible for the development of NIDDM, but NIDDM is the polygenic disease and most of NIDDM patients may have still-uncharacterized diabetogenic factors. PMID- 7983799 TI - [Candidate gene approach in Japanese NIDDM: liver/pancreatic beta cell type glucose transporter (GLUT2)]. AB - The liver/pancreatic beta cell type glucose transporter (GLUT2) is expressed in the pancreatic beta cell, a glucose carrier with a low affinity for glucose but a high capacity for glucose transport. The expression of GLUT2 in the normal pancreatic islet is increased after exposure to high glucose, while it is decreased in model animal with non-insulin-dependent diabetes mellitus (NIDDM). In Pima Indians, to assess the genetic components of the acute insulin response (AIR) and NIDDM, polymorphic dinucleotide repeat regions in the GLUT2 gene were evaluated. Robust sib-pair linkage analyses suggest linkage between GLUT2 and AIR, but no linkage was observed with NIDDM. The coding region of the GLUT2 gene was screened for mutations using polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) analysis. A single base change was identified in exon 3 in -5% of the study population. Although this base change resulted in an amino acid substitution (Thr110-Ile110), no significant association was noted between AIR and the mutation. We also screened for mutations using PCR-SSCP analysis in Japanese subjects. A single base silent polymorphism (Phe497, TTT-TTC) was identified in exon 10. Significant association was noted between TTC type and NIDDM (N = 78), compared to normal controls (N = 80). These data suggest the possibility that GLUT2 is one of the candidate genes for NIDDM. PMID- 7983800 TI - [Defects of candidate genes in Japanese NIDDM--glucose transporter gene(GLUT1 gene, GLUT4 gene)]. AB - To assess the contribution of GLUT1 and GLUT4 genes to NIDDM susceptibility in Japanese population, we performed population studies using RFLP markers. We found the strong association between XbaI polymorphism at GLUT1 gene and NIDDM, but no association between KpnI polymorphism at GLUT4 gene and NIDDM. Based on these results, molecular scanning of GLUT1 gene was performed using SSCP and direct sequencing in Japanese population, to substantiate the gene defect predisposing to NDDM. Although silent mutations were found, the meaningful mutations within the coding regions were not demonstrated. Thus the positive association observed in population study may be spurious or due to the abnormalities in non-coding regions such as promoter or other regulatory elements at GLUT1 gene. PMID- 7983801 TI - [Mutations of glucokinase gene in Japanese subjects with NIDDM]. AB - Glucokinase has been proposed to play an important role as a glucose sensor in pancreatic beta-cells. Mutations in the glucokinase gene have been shown to be the major cause of maturity-onset diabetes of the young (MODY) in Caucasian subjects. In population-association study with microsatellite DNA polymorphisms in Japanese subjects with NIDDM, a negative association was evident between NIDDM and the glucokinase gene locus, although contradictionary results were present. Using PCR-SSCP analysis, no glucokinase mutation, which induces changes in amino acid residues, was identified in Japanese subjects with classical late-onset NIDDM. These results suggest that mutations in this gene are not the major cause of common form NIDDM in Japanese. PMID- 7983802 TI - [Mutations in the mitochondrial gene in patients with NIDDM]. AB - Since the identification of an A to G mutation at position 3243 of mitochondrial leucine tRNA (3243 bp mutation) in families with diabetes and deafness, the prevalence, clinical characteristics, pathophysiology of diabetes associated with 3243 bp mutation have been studied in Japan. Our study has shown that diabetes cosegregates with 3243 bp mutation in more than 30 Japanese families and that the prevalence of 3243 bp mutation in randomly selected diabetic patients (0.9%, 5 out of 550) is significantly higher than that in non-diabetic controls without family history (0.0%, 0 out of 250). Diabetes mellitus with 3243 bp mutation is often accompanied by distinct clinical features such as maternal inheritance, hearing disturbance, insulin deficiency and tendency to progression and can be regarded as a new subtype of diabetes mellitus. PMID- 7983803 TI - [Insulin receptor gene in an etiology of Japanese NIDDM]. AB - We reviewed 23 Japanese patients with mutation in the insulin receptor gene. In general, patients with two mutant alleles tend to be more severely insulin resistant than those with one mutant allele. Most of the mutations have been identified in patients with genetic syndromes associated with extreme insulin resistance. However, some patients having a mutation in the insulin receptor gene (especially in the tyrosine kinase domain), were moderately insulin-resistant. In these cases, despite having a same mutation in the insulin receptor gene, some individuals exhibited significant clinical differences (e.g. insulin resistance or glucose tolerance). Although mutations in the insulin receptor gene can cause insulin resistance, we assume that other genetic or behavioral factors may alter the clinical phenotype in patients with same mutations in the insulin receptor gene. Nevertheless, mutations in the insulin receptor gene may be a contributory cause of insulin resistance in a subpopulation (approximately 1%) of NIDDM. PMID- 7983804 TI - [DNA polymorphism in the human glycogen synthase gene and non-insulin dependent diabetes mellitus in Japanese]. AB - Using PCR-RFLP analysis, no A2 allele which is related with the frequency of NIDDM in Finland was detected in Japanese patients with NIDDMs and controls. We found out a new microsatellite of CA repeat in the human muscle glycogen synthase (MGS) gene, and the polymorphism of the repeat number detected by the PCR. The allele frequency was not significantly different between NIDDMs and controls. However, the allele frequency in the patients without high total cholesterolemia was significantly different from that of controls, and 19 repeat allele was significantly higher in this group than that in controls. These suggest that the MGS gene or neighboring genes are related with one of the disease genes of diabetes mellitus without high total cholesterolemia. PMID- 7983805 TI - [Glycogen synthase gene-glycogen synthase gene in Japanese patients with NIDDM]. AB - As glycogen synthase is a key enzyme of the non-oxidative pathway of glucose metabolism in the skeletal muscle, and reduced activity of this enzyme is related to insulin resistance, it seems likely that this enzyme is a candidate gene for contributing to the pathogenesis of NIDDM. In this paper, we review recent findings of polymorphism of the human glycogen synthase gene, XbaI restriction enzyme length polymorphism and simple tandem repeat DNA polymorphism, and discuss the possible association between the glycogen synthase gene and NIDDM. PMID- 7983806 TI - [Human glucagon-like peptide-1 receptor gene in NIDDM]. AB - Glucagon-like peptide-1 (GLP-1) stimulate glucose dependent insulin secretion from beta-cells. Human cDNA and the gene of the receptor for the GLP-1 was isolated. Two polymorphic simple tandem repeats were found in the gene. Using these markers, role of GLP-1 receptor mutations in the pathogenesis of NIDDM was studied. No association was found between the marker alleles and NIDDM in African American or in Japanese. Linkage was rejected between the GLP-1 receptor gene and NIDDM in Caucasian late-onset NIDDM families and in French MODY families. Mutations in the GLP-1 receptor gene do not appear to be major genetic determinants of NIDDM. Further studies are required to exclude the minor role of the gene in a fraction of NIDDM patients. PMID- 7983807 TI - [Role of IAPP in the pathogenesis and development of NIDDM]. AB - Islet amyloid deposits are the characteristic lesions of the pancreas of the patients with non-insulin-dependent diabetes mellitus (NIDDM). Islet amyloid polypeptide (IAPP or amylin) is a 37 amino acid peptide, which was extracted and characterized from islet amyloid deposits in patients with NIDDM. Recent studies and characterization of IAPP cDNA suggest that IAPP is a normal islet hormone and is co-secreted with insulin from islet beta cells of the pancreas. In this paper, we review recent advance of the research for IAPP including our results, and discuss the role of IAPP in the development of NIDDM, and we propose a new type of diabetes, "amyloid diabetes". PMID- 7983808 TI - [Construction of transgenic mouse system expressing human islet amyloid polypeptide (IAPP)/amylin]. AB - To investigate the relationship between human islet amyloid polypeptide (IAPP)/amylin expression and islet amyloid deposits in the pathogenesis of human non-insulin-dependent diabetes mellitus (NIDDM), we generated transgenic mice using a human IAPP cDNA connected to an insulin promoter. Analyses by RNA blotting and immunohistochemistry revealed that the transgene was expressed exclusively in the pancreatic Beta-cells. Immunogold electron microscopy showed that the C-terminal flanking peptide of the human IAPP was localized in the Beta secretory granules. Reverse-phase HPLC demonstrated the presence of mature human IAPP. However, glucose tolerance was normal and amyloid formation was not observed in transgenic mice at 7 months of age. A longer time or other factors may be required for islet amyloid deposits and hyperglycemia to develop in mice. PMID- 7983809 TI - [Analysis of HLA-DR, -DQA1, -DQB1 genes in Japanese IDDM patients]. AB - Susceptibility to insulin-dependent diabetes mellitus (IDDM) is determined by both genetic and environmental factors. The major genetic susceptibility to IDDM is conferred by genes in the HLA class II region on chromosome 6. In Caucasians, this susceptibility is thought to be determined by DQA1 and DQB1 genes including the presence of arginine at position 52 of the DQ alpha chain and the absence of aspartic acid at position 57 of the DQ beta chain. In Japanese subjects, IDDM has been found to be associated DR, DQA1, and DQB1 genes. Positive associations with arginine at position 52 of the DQ alpha chain have been demonstrated in Japanese IDDM patients. However, the majority of Japanese IDDM patients do not show positive association to the absence of aspartic acid at position 57 of the DQ beta chain. Susceptibility to IDDM in Japanese subjects appears to be due to combination of DR genes and DQA1-DQB1 haplotypes. PMID- 7983811 TI - [Analysis of TAP gene in IDDM]. AB - Transporter associated with antigen processing (TAP) is a molecule required for endogenous antigen processing and is encoded in MHC class II region. We have typed TAP polymorphism in 95 patients with insulin-dependent diabetes mellitus (IDDM) and 75 normal controls. TAP alleles were typed by PCR-SSO method. There was no significant difference between IDDM patients and normal controls in the frequencies of TAP 1 and TAP 2 alleles. On the contrary, HLA-DQ locus showed strong association with IDDM in the same series of subjects. Positive linkage disequilibrium was observed between HLA-DQB1*0303 and TAP 2C, and HLA-DQB1*0401 and TAP 2B. Negative linkage disequilibrium was observed between HLA-DQA1*0103 and TAP 2A. We conclude that it is not TAP but HLA-DQ that exhibits primary association with IDDM. PMID- 7983810 TI - [Non-MHC susceptibility genes in Japanese subjects with insulin-dependent diabetes mellitus (IDDM)]. AB - Genetic factors clearly contribute to the development of autoimmune destruction of pancreatic beta cell in IDDM. The HLA class II genes have an important role in the pathogenesis of Japanese IDDM as they do in Caucasians. Particular HLA class II alleles and haplotypes contribute to the IDDM susceptibility/resistance in Japanese. In the 5' insulin gene polymorphism, the shorter insertion (class 1 allele) is predominant in Japanese, and thus is not associated with IDDM. Subdivision of the class 1 alleles also failed to show an association with Japanese IDDM. The insulin gene region appears not to be a valuable genetic marker for IDDM in Japanese. Recently, we found an association of polymorphism in the IFN-gamma gene with Japanese IDDM. PMID- 7983812 TI - [Analysis of T cell receptor gene of infiltrating T lymphocytes in the pancreas of insulin-dependent diabetic patients]. AB - Insulin-dependent diabetes mellitus (IDDM) develops mainly from the destruction of pancreatic beta cells by cytotoxic T lymphocytes. One of the key phenomena observed in the pancreas of IDDM patients is the destructive process of beta cells by cytotoxic T cells. In NOD mice, an animal model of IDDM, the T cell receptor (TCR) of the infiltrating T lymphocytes was reported to be variable. Our analysis of RNAs obtained from the pancreas of newly diagnosed IDDM patients using the RT-PCR method indicated that the repertoire of T cell receptor alpha was restricted. Clustering of conservative amino acid sequences was found in each patient. The elucidation of the TCR of T cells recognizing and destructing beta cells in IDDM would enable us to develop a novel method immunologically intervening the occurrence of IDDM. PMID- 7983813 TI - [Current studies on the identification of susceptibility genes for IDDM in NOD mice]. AB - Until recently, localization of genes involved in multifactorial diseases, such as diabetes, was thought to be impracticable. The recent development of microsatellite genetic markers detected by PCR has facilitated detailed genetic analysis of complex traits. Microsatellite markers have been utilized for genetic analysis of NOD mice which spontaneously develop autoimmune IDDM similar to the human disease. There is evidence for ten distinct loci that affect the development of insulitis and diabetes in NOD mice. One of these loci, designated Idd-1, has been linked to the MHC on chromosome 17. Transgenic mouse experiments have shown that Idd-1 is composed of MHC class II genes I-A beta and I-E alpha. PMID- 7983814 TI - [The results of coloesophagoplasty in childhood]. AB - Over a six-year period (1988 through 1993), a total of 380 children with congenital and acquired esophageal diseases undergo treatment in the Second Pediatric Surgery Clinic. Plastic replacement of esophagus using a graft from the colon is performed in 31 children. The indications and procedures for colo esophagoplasty in children are discussed. Two basic operative methods are employed--retrosternal transposition of the colon transplant (with preservation of the esophagus or in children with previous extirpation, as well as in children with esophageal atresia), or transhiatal (transabdominal) esophagectomy with simultaneous placement of the transplant into the esophageal bed. The underlying cases of early and late postoperative complications are analyzed. Emphasis is laid on the good results of the method described (operative lethality amounting to 9.7 per cent) accordingly considered as the most appropriate for children. PMID- 7983815 TI - [Biliary ileus]. AB - This is a report on nine cases presenting biliary ileus. All patients undergo operative management. Two female patients present Bouveret's syndrome. The inference is reached that gallstone induced intestinal obstruction is characterized by atypical clinical patterns, conditioning in turn the diagnostic difficulties encountered, and the necessity to undertake operative treatment against the background of advanced ileus. The latter is one of the rarest forms of intestinal obstruction. Biliary ileus treatment consists in the removal of small intestinal impatency. The concretion is pushed in oral direction, and its evacuation is successfully accomplished by enterotomy, duodenotomy or gastrotomy. Two fatal outcomes due to severe advanced form of ileus are reported. PMID- 7983816 TI - [The results of the long-term follow-up of an expanded variant of selective proximal vagotomy]. AB - This is a report on a long-term follow-up study of the results of an extended variant of proximal selective vagotomy in patients undergoing clinical approbation over periods ranging from 7 to 9 years. The details of technical implementation of the variant are described. At zero lethality and complete recovery of the patients followed up, the late results are estimated as excellent. PMID- 7983817 TI - [Biligenic hepatic and subhepatic abscesses--observations on 9 cases]. AB - This review presents 9 cases with pyogenic hepatic and subhepatic abscesses developed by biliary route. An ultrasonography and computed tomographic scan was performed on 3 patients. Eight patients were treated with open surgical drainage and one with percutaneous drainage under ultrasonic control. All of them received a triple antibiotic therapy. Five patients had diabetes mellitus. Mortality was null. PMID- 7983818 TI - [In situ femorodistal autovenous bypass]. AB - Bypass in-situ surgical technique was applied in 49 cases of femorodistal arterial reconstructions. The operative technical details, as well as intra- and postoperative complications are discussed. A patency of the bypass in 87.5% after 18-month following are documented as well as limb salvation in 97.6%. The technical advantage of the bypass in-situ method are discussed and a recommendation for its appliance in suitable cases is given. PMID- 7983819 TI - [7 cases of liver transplantation with preservation of the vena cava inferior]. AB - Orthotopic liver transplantation (OLT) with preservation of the inferior vena cava (IVC) was performed in 7 patients during a period of 7 weeks. For 5 years in this center are realized 180 OLT, the last 93 of them with preservation VCI (51.6%). This method had important advantages versus standard operation--blood loss and operating time are reduced, IVC does not clamped. This operation can be used in the majority of cases. PMID- 7983820 TI - [The Clinitron fluidized bed--its qualities and use]. AB - The basic properties and characteristic features of a unique therapeutic device- the "Clinitron" fluid bed--are described. Regardless of its comparatively late adoption in the clinic practice of this country, it is successfully used in the management of severe burns at the burn lesion department in the town of Plovdiv. Emphasis is laid on the many-sided qualities of Clinitron-therapy, practicable in the various fields of surgery. PMID- 7983821 TI - [The parascapular fasciocutaneous flap in the surgical treatment of deep burns in the axillary area]. AB - An original operative approach to severe defects of the axilla--periscapular fasciocutaneous flap according to Pontaine--is recommended. It is a matter of a procedure which surgeons dealing with the problems of plastic and reconstructive surgery become acquainted with for the first time. A classification of axillary defects, contributing to the most adequate choice of operative approach, is also suggested. Typical cases where this operative method is used are illustrated. PMID- 7983822 TI - [Mean body temperature during anesthesia in children with burns--its information value and use]. AB - In forty-four children with total body surface amounting to 0.4-0.6 sq. m., and burnt surface ranging from 6 to 60 per cent, measurements of the mean body temperature are done during anesthesia with halothane, methoxyflurane and ketamine. Group one is made of 14 children anesthesized with halothane, nitrous oxide and oxygen in conditions of controlled ventilation; group two--16 children anesthesized with methoxyflurane, nitrous oxide and oxygen under controlled ventilation, and group three--14 children subjected to intravenous ketamine anesthesia with spontaneous respiration. Rectal and skin temperatures are registered at 15-minute intervals in the course of two-hour-long anesthesia. The mean body temperatures are calculated. The study results point to a significant temperature reduction on the first and second hour, and after extubation, but there are no differences between the individual groups. The mean body temperature has low informative value, and is mainly applied in thermal balance assessment. PMID- 7983823 TI - [The intubation and anesthesiological problems of patients with burns and their sequelae]. AB - Patients with specific location of the burn lesion (head, face and neck) developing hypertrophic scars, adhesions, microstoma and other complications, are considered as high-risk patients in terms of analgesia. Not infrequently, it is a matter of the same patients in different developmental phases of the burn disease. Usually, the problems faced occur during intubation and implementation of a give type of anesthetic technique. The anesthesiologist must cope with the patient's individual peculiarities on a daily basis, and accordingly make a correct choice of the type of anesthesia. A male patient with deep facial burn, undergoing repeated surgical interventions using various types of anesthesia, is reported. The intubation and anesthesiologic problems in two children with burn sequels are discussed. PMID- 7983824 TI - [Progress in urology]. PMID- 7983825 TI - [Drug effects on the lower urinary tract to improve bladder emptying]. AB - Literature data about the pharmacologic effect exerted on the lower urinary pathways in various pathologic conditions are discussed with a special reference to the existing knowledge of neuroanatomy of the urinary bladder and proximal urethra. Specific drugs and dosage schemes, contributing to improve the act of miction following diverse operative interventions, leading to retention phenomena, as well as in conditions of the so-called "unstable detrusor", are recommended. The likelihood of a positive effect being exerted in various spastic conditions of the external sphincter urethrae muscle, due to neurologic diseases, is also assayed. PMID- 7983826 TI - [The effect of general anesthesia and its components on free-radical processes]. AB - The problem of free-radical production in biological objects is discussed with emphasis laid on the influence exerted by general anesthesia and its components on free-radical processes. Free radicals are characterized by enhanced biological activity and potentiality to damage cellular structures and composition of the biological membranes, with changes in enzyme activity resulting in cell function and substance metabolism impairment. It is of interest to note the pro-oxidant effect of some anesthetics and drugs used in the course of general anesthesia. Contemporary multicomponent general anesthesia is accomplished with the aid of a large number of drugs, having different physico-chemical properties, and affecting directly or indirectly the processes of peroxide oxidation of lipids in the body. The role of antioxidants in eliminating the adverse sequels of lipid peroxide oxidation disorders id comprehensively discussed under a separate heading. PMID- 7983827 TI - [The anesthesiological risk and treatment characteristics of patients with ischemic heart disease prepared preoperatively with beta-receptor blockers, calcium antagonists and nitro preparations]. AB - The anesthesiologic risk in ischemic heart disease (IHD) patients undergoing noncardiac surgery is determined by the duration of myocardial infarction sustained in the past, and the degree (severity) of stenocardia manifestations. Such risk is estimated as minimal within six months after myocardial infarction in the presence of stenocardia stabilization. In this contingent of patients the anti-ischemic therapy is proceeded with in both pre- and postoperative period. The role of beta-adrenergic blocking agents (propranolol, acebutolol, esmolol, sotalol) and calcium antagonists (nifedipine, diltiazem) in the prophylaxis against intraoperative myocardial ischemia, rhythm disorders and pathologic arterial pressure rise is definitely proved. PMID- 7983828 TI - [A case of urogenital schistosomiasis--a mask of acute scrotum]. PMID- 7983829 TI - [A rare case of malignant mesothelioma of the testicular coverings]. PMID- 7983830 TI - [Malignant lymphomas of the small intestine]. PMID- 7983831 TI - [Clinical studies in prostatic carcinoma]. AB - Carcinoma of the prostate is a widespread disease posing serious problems, especially when patient in stage T3-T4 are concerned. Proceeding from clinical observations on 269 patients presenting the aforementioned condition, and on the basis of thorough clinical, laboratory and histologic studies, a combined therapeutic approach using cyproterone acetate is adopted, supplemented by orchiectomy in some patients, and transurethral resection in others. After 3 month treatment course, changes in the level of microelements, copper, zinc and iron in particular, are recorded. In some cases the level of prostate specific antigen is lowered. Control of the underlying disease is successfully attained in 72 per cent of the patients. PMID- 7983832 TI - [A method for expanding the capacity of the bladder in microbladder]. PMID- 7983833 TI - [The Campos-Freire ureterovesicular anastomosis]. PMID- 7983834 TI - [The use of an absorbable mesh for splenography and reconstruction of the pelvic peritoneum]. PMID- 7983835 TI - [The new possibilities for the endoscopic treatment of malignant esophageal strictures by placing metal endoprostheses. 1]. PMID- 7983836 TI - [A method for reinforcing the cervical anastomosis in total esophagocoloplasty]. PMID- 7983837 TI - [Preoperative immunoprophylaxis in wound and urinary infections in urological patients with Urostim]. AB - In two groups of 25 urological patients each, with and free of urinary infection, Urostim is administered fifteen days before and after the operation. The prophylactic effect of the drug in terms of hospital transmitted wound and urinary infections is recorded on the basis of comparative study with control groups. As shown by the results obtained, Urostim immunoprophylaxis yields positive results in urological practice. In 80 per cent of the cases development of the complication is prevented. Vaccine administration in conjunction with an updated antibiotic broadens the therapeutic scope in patients with urinary infection. PMID- 7983838 TI - Hantavirus: an overview and update. PMID- 7983839 TI - Characterization of cilia-associated respiratory bacillus isolates from rats and rabbits. AB - Isolates of the cilia-associated respiratory (CAR) bacillus were harvested from the trachea of three naturally infected rats and five naturally infected rabbits and were grown on 3T3 mouse fibroblast cells. Isolates were compared by growth characteristics in mammalian cell culture, by use of protein and DNA analyses, and by experimental infections of BALB/c mice. Examination of CAR bacillus isolates by transmission electron microscopy indicated that organisms from rats and rabbits were similar in appearance and had an acidic mucopolysaccharide layer. In culture, the isolates from rats appeared larger than the rabbit isolates and formed large multiorganism aggregates, whereas isolates obtained from rabbits did not. Protein and antigenic analyses and DNA ribotyping revealed minor differences between isolates but could not be used to distinguish the rat from the rabbit isolates. Mice experimentally inoculated with CAR bacillus of rat origin developed interciliary colonization, seroconverted, and developed microscopic pulmonary lesions. Mice inoculated with isolates of rabbit origin did not display intraciliary colonization, seroconvert, or develop pulmonary disease. The findings of this study indicate that CAR bacillus isolates of rat and rabbit origins may be distinct strains and suggest that, in mice, isolates of rat origin may be more virulent than those of rabbit origin. PMID- 7983840 TI - Feline lymphoid tissues engrafted into scid mice maintain morphologic structure and produce feline immunoglobulin. AB - To adapt the feline immune system to a small laboratory animal host, severe combined immunodeficient (scid) mice were engrafted with neonatal feline lymphoid tissues, including lymph node, thymus, spleen, and bone marrow. Lymph node and thymus tissue were implanted subcutaneously within the mammary fat pad, and a single-cell suspension of spleen, thymus, and bone marrow was inoculated intraperitoneally (IP). Seven groups of mice (three mice per group) were engrafted on day 0, and members of one group were euthanatized weekly from 2 to 8 weeks after engraftment. For each mouse, graft morphology was evaluated by light microscopy, feline DNA was detected in peripheral blood by polymerase chain reaction (PCR) amplification of feline-specific DNA sequences, and serum IgG concentration was measured by ELISA. Ten of 13 feline grafts evaluated histologically between 3 and 8 weeks after engraftment contained large focal aggregates of lymphocytes bordered by plasma cells. Of 14 thymus grafts evaluated histologically during the same period, 5 were characterized by dense accumulations of small lymphocytes surrounding thymic epithelial cells. Two of these thymus grafts were indistinguishable from age-matched feline thymus. At 2 weeks after engraftment, feline lymph node and thymus contained extensive central necrosis bordered by a narrow zone of lymphocytes and small-caliber blood vessels.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7983841 TI - Chronic implantation of nonocclusive catheters and flow probes in the splanchnic and hindlimb vasculature of the rabbit. AB - Flow probes and nonocclusive catheters were simultaneously implanted in the splanchnic and hindlimb vasculature to measure regional blood flows and arteriovenous differences of individual organs in the conscious rabbit. Pulsed Doppler flow probes were constructed by modifying the technique of Haywood et al., and nonocclusive catheters were designed and constructed from Silastic tubing (0.6- or 0.9-mm OD) and surgical velour. Laparotomy was performed on rabbits under anesthesia, and the renal, mesenteric, iliac, or hepatic artery and portal vein were isolated and instrumented with a flow probe. A nonocclusive catheter was then inserted into the respective vein. Instrumentation of the hepatic system required probes on the hepatic artery and portal vein, and nonocclusive catheters were placed into hepatic and portal veins. One week later, rabbits were reanesthetized and nonocclusive catheters were inserted into the cranial vena cava via the jugular vein and abdominal aorta to the level of the celiac axis. Probes and catheters were evaluated daily up to 30 days. Implants remained functional for an average of 3 weeks, permitting chronic measurement of velocity and blood variables in individual tissue beds of the conscious rabbit. PMID- 7983842 TI - Porphyrinogenic effects of atracurium, vecuronium, and pancuronium in a primed rat model. AB - Steroidal muscle relaxants might theoretically be contraindicated in acute hepatic porphyrias. Atracurium, on the other hand, has been proposed as the muscle relaxant of choice because of its extrahepatic degradation. To further investigate this problem, equipotent doses of atracurium, vecuronium, and pancuronium were determined in male Sprague Dawley rats, using evoked electromyography. After this pilot study, 64 rats were anesthetized, mechanically ventilated, and randomly allocated to eight groups. Animals in groups 1 through 4 received an intraperitoneal injection of arachis-oil 20 h before the experiments. For groups 5 through 8, an experimental porphyria was induced by use of the chemical substance 3,5-dicarbethoxy-1,4-dihydrocollidine (DDC), which was dissolved in arachis-oil and given 20 h prior to the beginning of the study. Rats of groups 1 and 5 served as controls; they received saline and were not given muscle relaxants throughout the experiment. For groups 2 and 6, atracurium was administered at a dosage of 4 mg/kg of body weight, followed by a continuous infusion of 15 mg/kg/h. Animals of groups 3 and 7 received vecuronium at a dosage of 1.5 mg/kg, followed by 7.5 mg/kg/h. For groups 4 and 8, pancuronium was given (0.75 mg/kg and 2.5 mg/kg/h, respectively). At the end of the 3-h study period, the liver was perfused and excised, and urine was obtained. Activity of the hepatic enzyme delta-aminolevulinic acid synthase (ALAS) and urinary concentrations of delta-aminolevulinic acid (ALA) and porphobilinogen (PBG) were determined.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7983843 TI - Tarsal joint contracture in dogs with golden retriever muscular dystrophy. AB - Golden retriever muscular dystrophy (GRMD) is an X-linked myopathy homologous with Duchenne muscular dystrophy of human beings. Affected dogs have progressive clinical dysfunction due to muscle wasting and contractures. Deficits progress particularly rapidly between 3 and 6 months of age. To better characterize the role of contractures in this deterioration, the flexor surface, nonweight-bearing tarsal joint angle was measured in GRMD-affected dogs and clinically normal littermates at both ages. The mean +/- SD tarsal joint angle for clinically normal dogs decreased from 164.6 +/- 6.09 degrees to 145.6 +/- 8.80 degrees between 3 and 6 months (P < 0.0005). The value for GRMD-affected dogs decreased from 153.3 +/- 11.44 degrees to 117.6 +/- 24.55 degrees (P < 0.005). The angle for clinically normal dogs was greater than that for GRMD-affected dogs at both ages (P < 0.05 at 3 months and P < 0.01 at 6 months). The decrease in tarsal joint angle, at times to less than 90 degrees, correlated well with other phenotypic features of GRMD, such as loss of the ability to walk. PMID- 7983844 TI - Ophthalmologic observations in the young Yucatan micropig. AB - Complete ocular examinations, including external observations of the eye and its adnexae, pupil responses to light stimuli (direct and consensual), anterior ocular segment examinations with the biomicroscope, and fundic examinations performed with an indirect ophthalmoscope were carried out on 112 7- to 12-month old Yucatan micropigs to evaluate the incidence of observed ocular abnormalities. Most of the ocular defects seen were classified as remnants of embryologic vascular tissue. Some findings were considered as congenital changes and the others of indeterminate origin in the absence of further pathologic examinations. The principal ocular abnormalities observed were, in decreasing order of incidence: hyaloid remnants (82.1%), pupillary membrane remnants (66.1%), incomplete pigmentation of the fundus with appearance of choroidal vasculature (tigroid fundus: 50.0%), and posterior cortical pinpoint opacities of the lens (20.5%). Ten older animals (five aged 15 to 18 months and five aged 19 to 33 months) were examined to evaluate any possible evolution of these findings. PMID- 7983845 TI - Granulomatous inflammation of the oropharyngeal cavity as a possible cause for unexpected high mortality in a Fischer 344 rat carcinogenicity study. AB - An unexpected, high, test-substance-unrelated mortality has been found predominantly in female Fischer 344 rats of a 2-year gavage carcinogenicity study, which is still in the active phase. Most of the dead animals (53%) had an impacted food or bedding bolus in the oropharyngeal cavity. Histologic evaluation of this area revealed a calcified, granulomatous inflammation of the sero mucinous glands (60%), frequently accompanied by papillary projections (50%) into the lumen. Additionally, decentral islet formation of the tracheal cartilage was evident in all animals examined. We assume that the partial blockage of the oropharyngeal lumina was the cause of death, because other possible factors were ruled out. To detect a possible strain-related predisposition, Fischer 344 and Sprague Dawley rats that had been used for technician gavage training were studied. Granulomas and papillary projections, as well as the decentral islet formation in the tracheal cartilage, however, were found in gavaged Fischer 344 but not Sprague Dawley rats. We consider the high mortality to be related to three factors: a predisposition of the Fischer 344 rat strain, an unphysiological pH of the solvent (pH 10), and chronic irritation due to an inflexible, metallic gavage tube. PMID- 7983846 TI - Removal of a trauma-inflicting alpha matriline from a group of rhesus macaques to control severe wounding. AB - Wounding in an 83-member group of rhesus macaques (Macaca mulatta) housed at the Yerkes Regional Primate Research Center Field Station became excessive to the point that intervention was deemed necessary. When observations indicated that three females from the group's alpha matriline were principally responsible for the wounding, the matriline (N = 7) was removed from the group. This study was conducted to document an atypical pattern of wounding in this group and to evaluate the effectiveness of removal as a procedure for controlling injuries. The aggression rates of 21 adult subjects and the wounds of all group members were recorded before and after the removal procedure and compared with those in a similar-sized group. Removing the alpha matriline did not alter aggression rates in the group or the rank order among the remaining matrilines. Aggression rates in the experimental group were also not significantly different from those in the comparison group before or after the removal. With the alpha matriline present, wounding levels in the group were significantly higher than those in the comparison group. After removal of the matriline, the frequency of wounds decreased significantly to levels similar to those of the comparison group. The pattern of excess wounding attributed to the extracted alpha females was idiosyncratic, involving removal of large patches of skin from the hindquarters of adult females or removal of the distal portion of the fingers, toes, or tail from juveniles.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7983847 TI - Temperament differences between captive Indian and Chinese-Indian hybrid rhesus macaque neonates. AB - Anecdotal evidence has accumulated from research and animal care personnel regarding the aggressive behavior reported in captive rhesus macaques originating in China. In this study, we compared neonatal temperament, activity, and neuromotor reflexes in 13 Chinese-Indian hybrid and 29 Indian-derived nursery reared infants. Neonatal assessments were conducted on days 7, 14, 21, and 30, using a test based on the Brazelton Neonatal Assessment Scale developed for use in human newborns. Hybrid infants had lower scores for all items pertaining to orientation and ability to sustain attention. They were also rated as more temperamentally reactive and irritable than the Indian-derived infants. These results suggest that constitutional factors may underlie some of the behavioral differences observed in Chinese- and Indian-origin adults and that these qualities emerge very early in life. PMID- 7983848 TI - Cerebrospinal fluid collection in rats: modification of a previous technique. AB - Modification of a previously published technique for cerebrospinal fluid collection in rats is described. This technique uses general anesthesia, a supporting platform to flex the head-neck junction, a surgical approach to the dorsal atlanto-occipital region, and a micromanipulator to hold and control the approach of the collection needle. Critical steps for success of the procedure are correct positioning, avoiding premature incision of the subarachnoid space, and alignment of the collection needle with the midline and longitudinal axis of the head. The authors had a 95% success rate in obtaining > 0.1 ml of cerebrospinal fluid, using this technique. PMID- 7983849 TI - Rapid and simple cannulation technique for repeated sampling of cerebrospinal fluid in the conscious rabbit. AB - A cannulation technique for continuous sampling of cerebrospinal fluid in unanesthetized freely moving rabbits was established. A permanent Teflon catheter constructed easily and inexpensively from commercially available material was placed into the cisterna magna and fixed to the skull by anchoring screws and dental cement. The surgical procedure required a minimum of time and induced minimal trauma, allowing studies in which physiologic conditions are required. The Teflon catheter induced minimal foreign body reaction, the system had minimal dead volume, and its size was small enough to allow the simultaneous implantation of other devices. PMID- 7983850 TI - Ultrasound-guided cholecystocentesis in the owl monkey. AB - Bile samples were obtained from adult owl monkeys by ultrasound-guided percutaneous cholecystocentesis, using a transhepatic approach. Sampling frequency was once weekly over a 5-week period. Clinical recovery from each procedure was rapid. Animal body weights fluctuated within 22% of baseline over the study period, but maximal weight loss in any animal was less than 3% at the study's end. At necropsy, gross lesions in the liver and gallbladder were minimal. Histologic examination revealed mild focal cholecystitis in the gallbladder of four of six animals, focal pericholecystitis in three of six animals, and foci of gallbladder fibrosis in two animals. Changes were consistent with repeated trauma from the centesis procedure. Gallbladder mucosa was judged normal in all animals. Body weight fluctuations were attributed to a change in diet, part of a concurrent study, rather than to the centesis procedure. Ultrasound-guided cholecystocentesis provides a rapid, minimally traumatic, and safe method for repeated bile sampling in a small nonhuman primate. PMID- 7983851 TI - Effects of carbon dioxide-induced anesthesia on cholinergic parameters in rat brain. AB - We report that acetylcholinesterase (AChE) and choline acetyltransferase (ChAT) activities in rat brain were virtually identical whether the rat was anesthetized with carbon dioxide (CO2) before decapitation or decapitated without prior sedation. The AChE and ChAT activities were measured in three brain regions: the hippocampus, cerebral cortex, and cerebellum. Enzyme activities varied significantly by brain region, with the highest values in the hippocampus and the lowest values in the cerebellum. Enzyme activities, however, did not vary with the method of euthanasia, either CO2-induced anesthesia prior to decapitation or decapitation without anesthesia. These data suggest that CO2-induced anesthesia prior to decapitation does not alter activities of these cholinergic markers in rat hippocampus, cerebral cortex, and cerebellum. This method of euthanasia eliminates the need to capture a conscious animal, which reduces stress to the animal and the experimenter. PMID- 7983853 TI - Isolation of Streptococcus equisimilis from abscesses detected in specific pathogen-free mice. PMID- 7983852 TI - Diagnostic exercise: meningoencephalitis in Macaca fascicularis. PMID- 7983854 TI - Malignant melanoma in two rabbits. PMID- 7983855 TI - Imperforate vagina and mucometra in inbred laboratory mice. PMID- 7983856 TI - Increased incidence of diabetes mellitus in specific pathogen-eliminated offspring produced by embryo transfer in NOD mice with low incidence of the disease. PMID- 7983857 TI - Lesions of sternal and growth plate cartilage in beagles. PMID- 7983858 TI - Changes in the cholinergic neurochemical parameters in regional brain areas of Wistar rats aged 3 (weanling), 10 (mature) and 119 (old age) weeks. PMID- 7983859 TI - Metastasizing squamous carcinoma arising in a giant condyloma of Buschke Loewenstein. PMID- 7983860 TI - Prosthetic cranioplasty infection due to Sporobolomyces. AB - I have presented an unusual case of an infected prosthetic cranioplasty due to Sporobolomyces species found to be sensitive to amphotericin B in vitro. The infection was successfully treated with a combination of surgery and antifungal therapy. PMID- 7983861 TI - Transformation of an internal medicine residency program to address the health of the Tennessee public. PMID- 7983862 TI - Detrusor instability--an overview. PMID- 7983863 TI - Isolated blunt renal trauma in a pediatric patient. PMID- 7983864 TI - The varied manifestations of disseminated gonococcal infection. PMID- 7983865 TI - Ehrlichiosis. PMID- 7983866 TI - Physician-to-physician communication. PMID- 7983867 TI - Mitigating the effects of severe weather and prolonged power failure on health care institutions. PMID- 7983868 TI - The Great American Smokeout: helping patients kick the habit. PMID- 7983869 TI - The Great American Smokeout. PMID- 7983870 TI - The St. Jude Medical valve. Experience with 1,000 cases. AB - We analyzed the long-term results of valve replacement with the St. Jude Medical bileaflet valve (St. Jude Medical, Inc., St. Paul, Minn.) in our first 1000 implantations between 1978 and 1992. A total of 399 patients had mitral valve replacement, 471 aortic valve, and 130 double (mitral and aortic) valve replacement. The average patient age was 64 +/- 15 years and the majority of patients (52%) had concomitant coronary disease. With 4328 patient-years of follow-up, 83% of the mitral group, 76% of the aortic group, and 77% of the double valve group were free of thromboembolism at 10 years after operation, and 87% of the mitral group, 82% of the aortic group, and 85% of the double valve group were free of valve-related hemorrhage. At 10 years, 91% of the mitral group, 84% of the aortic group, and 84% of the double valve group were free of valve-related death. However, overall survival at 10 years was only 42% +/- 4% for the mitral group, 43% +/- 4% for the aortic group, and 43% +/- 6% for the double valve group. For all three groups, age was a highly significant factor stratifying survival (p < 0.001), as was the presence of coronary disease (all p < 0.001). The excellent freedom from valve-related death at 10 years of 84% to 91% is in striking contrast to the overall survivals of 42% to 43% at 10 years. This difference suggests that the primary factors limiting long-term survival after valve replacement with the St. Jude Medical valve are not valve-related factors, but other patient factors such as age and concomitant coronary disease. PMID- 7983871 TI - Long-term results of valve replacement with the St. Jude Medical valve. AB - Between 1980 and 1992, 908 patients underwent single aortic (n = 178), single mitral (n = 577), or double aortic and mitral (n = 153) valve replacement with the St. Jude Medical valve at our hospital. There were 392 male patients and 516 female patients whose ages ranged from 1.2 to 74 years (mean, 52 years). The early mortality rate was 5.0% (45 patients). A 94% complete follow-up was accomplished for 863 patients who were discharged from the hospital (4682.3 patient-years). Sixty-nine of these patients died, for a late mortality rate of 8.0%. Fifty-two patients, including four patients (0.3%/100 patient-years) had anticoagulant-related hemorrhage, 4(0.1%/100 patient-years) had prosthetic valve endocarditis, 11 (0.2%/100 patient-years) had nonstructural valve dysfunction, and 16 (0.3%/100 patient-years) underwent reoperation. There were no structural valve failures in this series. The total number of valve-related deaths was 22. Of those patients who survived, 98% were in New York Heart Association functional class I or II at the date of the last follow-up. The probabilities of freedom from thromboembolism and anticoagulant-related hemorrhage at 10 years were 94% +/ 2% and 97% +/- 2% in aortic valve replacement, 89% +/- 2% and 98% +/- 4% in mitral valve replacement, and 89% +/- 6% and 92% +/- 6% in double valve replacement, respectively. Significant hemolysis related to the St. Jude Medical valve occurred in 8 of the 577 patients who received mitral valve replacement in our early experience, and modifying the valve orientation appeared to play an important role in reducing hemolysis. The event-free rate, including all complications and late deaths, at 10 years was 75% +/- 7%, 74% +/- 3%, and 81% +/ 6% in aortic valve replacement, mitral valve replacement, and double valve replacement, respectively. On the basis of these results, the St. Jude Medical valve seems to be an excellent mechanical valve in terms of durability and low thrombogenicity and remains our prosthetic valve of choice when valve replacement with a mechanical valve is indicated. PMID- 7983872 TI - Aortic valve replacement with a stentless porcine aortic valve. A six-year experience. AB - A stentless porcine aortic valve was used for aortic valve replacement in 123 patients from 1987 to 1993. The mean age of 86 men and 37 women was 61 +/- 12 years. Most patients had aortic stenosis; one-third had coronary artery disease and six had mitral valve disease. The stentless valve was secured in the subcoronary position by the same technique used for a freehand aortic valve homograft. The size of valve was based largely on the diameter of the sinotubular junction of the aortic root. The mean valve size was 26.5 mm (range 19 to 29 mm) and 87% were 25 mm or larger. Two operative deaths occurred, one the result of myocardial infarction and the other the result of infective endocarditis. Patients have been followed up from 3 to 77 months, mean 22 months. Three late deaths, none related to the valve, have occurred. The actuarial survival at 6 years was 91% +/- 4%. Four transient cerebral ischemic events have occurred, but two patients had extracranial cerebrovascular disease. One patient had endocarditis late in the postoperative period and required reoperation. All patients had Doppler echocardiographic studies before discharge from the hospital, 3 to 6 months later and annually. Only 15 patients have aortic insufficiency, trivial in 6 and mild in 9. The peak and mean systolic gradients decreased significantly during the first 3 to 6 months after implantation (p < 0.001), and the effective valve areas increased significantly during this time interval (p < 0.001). This improvement in valve hemodynamics is believed to be due to remodeling of the aortic root and regression of left ventricular hypertrophy. The results of aortic valve replacement with this stentless bioprosthesis have been excellent and justify its continued use in older patients. PMID- 7983873 TI - Biomechanics of glutaraldehyde-treated porcine aortic roots and valves. An investigation of the effect of predilation of the elastic aortic root. AB - The biomechanics and function of fresh porcine aortic roots and valves have been compared with those of glutaraldehyde-treated roots prepared in a conventional manner without dilation of the elastic aortic root and with glutaraldehyde treated roots prepared with permanent predilation during fixation. The glutaraldehyde-treated aortic walls were significantly less extensible than fresh walls, with a mean dilation of only 6% compared with 45% for the fresh root at 120 mm Hg pressure. Permanent predilation of the aortic root during fixation allowed the total dilation of the fixed root to be increased to 19% at 120 mm Hg pressure. The effective orifice area of the fresh root and valve was significantly greater than those of the fixed roots and valves, with permanent predilation fixation producing a significantly greater orifice area than conventional fixation. The open-leaflet bending deformations were found to be lower in the valves fixed after permanent predilation than in the standard fixed valves. The glutaraldehyde-treated porcine root and valve does not reproduce the biomechanics and function of the fresh/root, because of the reduced extensibility of the fixed aortic wall. Permanent predilation during fixation helps to partially overcome the shortcomings of the fixed root, producing better function than a standard fixed valve. PMID- 7983874 TI - Cox maze procedure for chronic atrial fibrillation associated with mitral valve disease. AB - Between April 1992 and October 1993, we combined a modified maze procedure with mitral valve repair (n = 26) or replacement (n = 36) in 62 patients with atrial fibrillation, including 16 patients undergoing reoperation. Associated procedures included aortic valve operation (n = 22), tricuspid annuloplasty (n = 28), atrial plication (n = 10), and others (n = 3). Duration of atrial fibrillation varied from 0.1 to 23 years (average 8.3 +/- 6.4 years), the f-wave voltage ranged from 0 to 0.45 mV (0.16 +/- 0.09 mV), and cardiothoracic ratio varied from 46% to 85% (64% +/- 9%). We modified the maze atriotomies to preserve the sinus node artery and used cryoablation to simplify procedures. Aortic crossclamp time was 142 +/- 25 minutes and cardiopulmonary bypass time 226 +/- 34 minutes. No early or late deaths occurred in a total of 783 patient-months of follow-up. In 52 patients (84%) who regained atrial rhythm, an atrial A-wave was detected in 84% for transtricuspid flow and in 71% for transmitral flow. One patient with sinus rhythm had an episode of transient neurologic ischemia 4 months after mechanical valve implantation. The 10 patients who remained in atrial fibrillation had preoperative fibrillation for a significantly longer time than the rest of the patients with atrial rhythm (14.8 versus 7.2 years p < 0.001) and a larger left atrial dimension (70 versus 58 mm, p < 0.01). Nonetheless, no variable alone could have predicted postoperative rhythm for individual patients. The results suggest that the maze procedure is safe and effective and therefore should be considered for patients with chronic atrial fibrillation undergoing mitral valve operations. PMID- 7983875 TI - Indications for and results of single, bilateral, and heart-lung transplantation for pulmonary hypertension. AB - The indications for single, bilateral, and heart-lung transplantation for patients with pulmonary hypertension remain controversial. We retrospectively analyzed the results from 11 single, 22 bilateral, and 24 heart-lung transplant procedures performed between January 1989 and January 1993 on 57 consecutive patients with pulmonary hypertension caused by primary pulmonary hypertension (n = 27) or Eisenmenger's syndrome (n = 30). Candidates with a left ventricular ejection fraction less than 35%, coronary artery disease, or Eisenmenger's syndrome caused by surgically irreparable complex congenital heart disease received heart-lung transplantation. All other candidates received single or bilateral lung transplantation according to donor availability. Although postoperative pulmonary artery pressures decreased in all three allograft groups, those in single lung recipients remained significantly higher than those in bilateral and heart-lung recipients. The cardiac index improved significantly in only the bilateral and heart-lung transplant recipients. A significant ventilation/perfusion mismatch occurred in the single lung recipients as compared with bilateral and heart-lung recipients because of preferential blood flow to the allograft. Graft-related mortality was significantly higher and overall functional recovery as assessed by New York Heart Association functional class was significantly lower at 1 year in the single as compared with bilateral and heart-lung recipients. Thus bilateral lung transplantation may be a more satisfactory option for patients with pulmonary hypertension with simple congenital heart disease, absent coronary arterial disease, and preserved left ventricular function. Other candidates will still require heart-lung transplantation. PMID- 7983876 TI - Heterotopic pig model for direct revascularization and venous drainage of tracheal allografts. Paris-Sud University Lung Transplantation Group. AB - A macrosurgical technique of thyrotracheal harvesting and direct revascularization with and without venous drainage in a heterotopic thyrotracheal and immunosuppressed allograft in the pig model is described. Harvesting included en bloc cervicothoracic exenteration of the aortic arch and its supraortic trunks, anterior vena cava, jugular veins, subclavian vessels, thyroid gland, cervicothoracic trachea, and esophagus. This technique conserves the tracheal arterial supply provided by either the right or left subclavian artery, directly or indirectly via the inferior thyroid artery, and venous return provided by the anterior vena cava, directly or indirectly via the descending cervical vein. In recipients, implantation included (1) arterial end-to-end anastomoses of the proximal and postscalenic stumps of donor's subclavian artery to the proximal and prescalenic stumps of recipient's subclavian artery; (2) end-to-side venous anastomosis of the donor's anterior vena cava to the recipient's brachiocephalic venous trunk; and (3) heterotopic implantation of the proximal and distal orifices of the grafted trachea into the neck. Ten adult Large White pigs underwent direct revascularization of a thyrotracheal allograft with (n = 6, group 1) and without (n = 4, group 2) venous drainage. All grafts of group 2 exhibited a venous infarction, extensive inferior thyroid artery thrombosis, and ischemic and suppurative thyrotracheal necrosis 1 to 2 days after transplantation. In group 1, the length of the grafted trachea and number of rings were 9.75 +/- 1.5 cm and 22.1 +/- 3.3, respectively; ischemic time was 236.3 +/- 338.3 minutes. Group 1 pigs were put to death 4 (n = 4) and 3 (n =2) weeks after transplantation. All tracheal grafts had histologically normal airway epithelium; isolated areas of necrotic ischemia of the chorion and submucosa lasted for the first 7 days after transplantation but disappeared after epithelial regeneration. Premortem angiograms showed that all vascular anastomoses were patent. Grafts were histologically normal at postmortem examinations and all but one had no rejection. This large animal model demonstrates that long tracheal allografts might be transplanted by means of this direct revascularization and venous drainage technique. PMID- 7983879 TI - The direct effects of protamine sulfate on myocyte contractile processes. AB - The use of protamine sulfate in patients has been associated with circulatory collapse and is suspected to directly depress left ventricular function. However, the cellular basis for these changes that occur after protamine administration are unknown. Accordingly, the first objective of this study was to determine the direct effects of protamine on isolated myocyte contractile function. Myocytes were isolated from porcine hearts and contractile function was examined at baseline and then after the administration of protamine in concentrations of 20, 40, or 80 micrograms/ml. These concentrations were chosen because they reflect the serum concentrations of protamine commonly obtained in patients. The presence of protamine resulted in a dose-dependent decline in myocyte contractile function. For example, in the presence of a 20 microgram/ml concentration of protamine myocyte contractile function did not change significantly from baseline values, whereas an 80 microgram/ml protamine concentration caused myocyte percent and velocity of shortening to fall by more than 35% from baseline values. In light of the fact that protamine directly depressed myocyte contractile function, a second objective of this study was to examine potential cellular mechanisms responsible for this effect. Accordingly, in the next series of experiments, the effects of protamine on the myocyte sarcolemmal beta-adrenergic receptor system were examined by measuring myocyte contractile function with the beta-adrenergic agonist isoproterenol (25 nmol/L), as well as with the concomitant addition of protamine and isoproterenol. In the presence of protamine, myocyte beta adrenergic responsiveness was significantly reduced. For example, in the presence of an 80 microgram/ml dose of protamine, both myocyte percent and velocity of shortening fell by greater than 50% when compared with isoproterenol alone values (p < 0.05). To determine the reversibility of these protamine effects, we performed additional experiments in the presence of heparin. Incubation with heparin before protamine addition prevented the negative effects of protamine on myocyte function. However, the addition of heparin after protamine incubation failed to reverse the negative effects of protamine on myocyte function. In a final set of experiments, the effects of protamine on isolated myocyte electrophysiologic properties were examined using microelectrode techniques at baseline and with either 40 or 80 micrograms/ml doses of protamine. Myocyte resting membrane potential changed from baseline with the addition of a 40 micrograms/ml dose of protamine (-79.2 +/- 0.5 versus -75.2 +/- 0.8 mV (p < 0.05), with no further change at an 80 micrograms/ml dose of protamine (-73.0 +/- 1.3 mV).(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 7983877 TI - Comparison of activated coagulation time and whole blood heparin measurements with laboratory plasma anti-Xa heparin concentration in patients having cardiac operations. AB - Previous reports suggest that activated clotting times do not correlate with heparin concentration during cardiopulmonary bypass. This study was designed to compare whole blood heparin concentration and activated clotting time measurements with laboratory-based plasma heparin concentration. Sixty-two patients having cardiac operations requiring cardiopulmonary bypass were enrolled in this study. The study was conducted in two phases. In phase I of this trial, blood specimens were obtained from 30 patients before heparin administration and after each of three heparin doses (20, 80, and 150 U/kg). In phase II, blood specimens were obtained from 32 patients before heparin administration and 10 minutes after each of the following: heparin administration (250 or 300 U/kg), initiation of cardiopulmonary bypass, achievement of hypothermia, initiation of rewarming, and immediately before discontinuation of bypass. Blood specimens were used to measure activated clotting time (kaolin and celite), whole blood heparin concentration, and anti-factor Xa plasma heparin concentration. In phase I, activated clotting time (celite: r = 0.91; kaolin: r = 0.93) and whole blood heparin concentration (r = 0.98) measurements correlated well with plasma heparin concentration. After initiation of cardiopulmonary bypass (phase II), weak correlations for activated clotting time measurements (celite: r = 0.34; kaolin: r = 0.59) and a strong correlation for whole blood heparin concentration (r = 0.95) were evident when compared with plasma heparin concentration. During bypass, activated clotting time measurements also inversely correlated with temperature (celite: r = -0.21; kaolin: r = -0.19) and hematocrit (celite: r = 0.26; kaolin: r = -0.21). A weak correlation between activated clotting time measurements and plasma heparin concentration is evident during the cardiopulmonary bypass period, probably because of the influence of both reduced hematocrit and temperature on the activated clotting time assay. In contrast, whole blood heparin measurements correlate well with plasma heparin concentration before and during bypass. Further studies are needed to determine whether maintaining heparin levels during cardiopulmonary bypass by monitoring heparin concentration is more effective in preventing consumptive activation of the hemostatic system, reducing bleeding, and minimizing the use of blood products after cardiopulmonary bypass when compared with a protocol based on activated clotting time. PMID- 7983878 TI - Pulmonary microvascular responses to protamine and histamine. Effects of cardiopulmonary bypass. AB - Total cardiopulmonary bypass with associated reduced pulmonary blood flow causes significant alterations of endothelium-dependent pulmonary microvascular responses after resumption of normal perfusion. To determine if this change in pulmonary vascular reactivity may influence the responses of pulmonary arterioles to protamine and histamine, we examined isolated pulmonary microvessels after cardiopulmonary bypass. Sheep were heparinized, cannulated, and placed on either total bypass without ventilation or partial bypass (70% of baseline pulmonary arterial flow) with continued ventilation. After 90 minutes, sheep were separated from cardiopulmonary bypass and the lungs were perfused normally for 60 minutes. Vessels from noninstrumented sheep were used as controls. Peripheral pulmonary arterioles (90 to 190 microns) were cannulated, pressurized (20 mm Hg) in a no flow state, and examined with video microscopy. After precontraction of vessels with the thromboxane A2 analog U46619 by 18% to 25% of the baseline diameter, vasoactive agents were applied. Protamine sulfate, histamine, heparin, and the protamine-heparin complex caused significant dose-dependent relaxations of control pulmonary microvessels. These relaxation responses were substantially reduced or converted to contractile responses in endothelium-denuded vessels, which suggests that these relaxations are mediated through endothelium-dependent mechanisms. After partial bypass, responses to protamine and histamine were slightly reduced compared with the respective responses of control vessels, whereas the relaxation to protamine-heparin complex was not significantly altered. After total bypass, relaxation responses to protamine and protamine heparin complex were markedly reduced, whereas histamine induced contraction of pulmonary microvessels. Endothelium-independent relaxation to sodium nitroprusside was not affected by partial cardiopulmonary bypass and was slightly reduced after total bypass. A reduced direct vascular relaxation response to protamine and increased contractile response to histamine (or other humoral substances released during the systemic administration of protamine sulfate) may contribute to the elevation of pulmonary vascular resistance during infusion of protamine after cardiopulmonary bypass. PMID- 7983880 TI - Myocardial distribution of retrograde cardioplegic solution assessed by myocardial thallium 201 uptake. AB - Perfusion of the right ventricular myocardium with retrograde infusion of cardioplegic solution through the coronary sinus has been reported to be less than optimal. To study left and right ventricular perfusion during retrograde and antegrade coronary sinus cardioplegia, we added 0.5 mCi of thallium 201 to 500 ml of hyperkaliemic crystalloid cardioplegic solution injected retrogradely into the coronary sinus at low perfusion pressure (20 to 40 mm Hg) in 14 dogs and antegradely in the ascending aorta in seven dogs. The cardioplegic solution was cold (4 degrees C) in eight animals perfused retrogradely and warm (21 degrees C) in 13 animals. After aortic crossclamping, the ascending aorta and the left and right ventricles were vented and cardioplegic solution was injected retrogradely into the coronary sinus. Antegrade injections were performed after aortic crossclamping and venting of the left and right ventricles and of the left and right atrium. After cardioplegic arrest, the heart was harvested, fixed, and scanned with a gamma camera. With cold retrograde cardioplegia, 82% +/- 5% of the injected thallium 201 activity was identified in the myocardium--71% +/- 9% for warm retrograde perfusion and 80% +/- 3% for antegrade perfusion (p > 0.05). Focal areas of hypoactivity in the septum and in the right ventricular free wall were present at scintigraphic imaging in all animals receiving retrograde perfusion. In conclusion, most thallium 201 activity of cardioplegic solution injected retrogradely in the coronary sinus was identified in the myocardium, but focal areas of hypoactivity in the septum and in the right ventricular free wall were present, indicating uneven distribution. Temperature of the crystalloid solution had no effect on the myocardial distribution of the thallium 201 radiotracer in the myocardium. PMID- 7983881 TI - Evaluation of regional myocardial perfusion in areas of old myocardial infarction after revascularization by means of intraoperative myocardial contrast echocardiography. AB - Because myocardial revascularization to areas of old myocardial infarction brings about functional recovery to some extent to myocytes in those areas, the assessment of regional myocardial perfusion on those areas after myocardial revascularization may allow myocardial viability to be estimated. Using intraoperative myocardial contrast echocardiography by direct injection of 2 ml sonicated 5% human albumin into saphenous vein grafts, we assessed regional myocardial perfusion in 16 revascularized areas of old myocardial infarction. We estimated the myocardial viability of areas with respect to myocardial perfusion, and we compared these results to both the improvement of regional wall motion after myocardial revascularization (increase in segmental wall thickening during systole) and relative thallium 201 activity obtained by quantitative analysis of preoperative exercise myocardial thallium 201 distribution on delayed images. The background-subtracted peak peak intensity of myocardial enhancement and the ratio of endocardial to epicardial intensity were determined in each revascularized area. An inverse correlation existed between peak intensity (18 +/- 7) and the endocardial/epicardial ratio (0.88 +/- 0.17) (r = -0.63, p < 0.01). A good correlation was found between peak intensity and both the percent increase in segmental wall thickening (r = 0.73, p < 0.005) and the relative thallium 201 activity (r = 0.81, p < 0.005). These results suggested that regional myocardial perfusion after myocardial revascularization in areas of old myocardial infarction distributed better to the epicardial halves than to the endocardial halves, and that the peak intensity could be related to myocardial viability. PMID- 7983883 TI - p53 immunoreactivity in Barrett's metaplasia, dysplasia, and carcinoma. AB - Barrett's esophagus is a metaplastic condition with an unpredictable potential for neoplasia. Mutations of the tumor-suppressor gene p53 have been implicated in the evolution of some carcinomas. These mutations frequently result in intranuclear protein accumulation, which can be detected immunohistochemically. This study was undertaken to determine whether p53 immunoreactivity in Barrett's esophagus is a marker of neoplasia and, if so, when it occurs in the metaplasia dysplasia-carcinoma sequence. Twenty-eight esophageal resection specimens were studied. Barrett's mucosa was present in each specimen, low-grade dysplasia in 27, high-grade dysplasia in 26, intramucosal cancer in 18, and submucosal cancer in 5. Immunohistochemical staining with the monoclonal antibody Pab1801 was used to detect the intranuclear protein product of mutated p53. No p53 immunoreactivity was seen in specimens of Barrett's mucosa or low-grade dysplasia. p53 immunoreactivity was found only in specimens of high-grade dysplasia, intramucosal cancer, and submucosal cancer. Sixty-nine percent (18/26) of these specimens exhibited mutated p53; 18 of 26 specimens of high-grade dysplasia (69%), 12 of 18 intramucosal cancer specimens (67%), and two of five submucosal cancer specimens (40%) expressed mutated p53. When p53 staining was observed, the spectrum of neoplastic changes (high-grade dysplasia, intramucosal cancer, submucosal cancer) within the specimen was positive. We conclude that (1) p53 immunoreactivity in Barrett's esophagus is a frequent, but not inclusive, marker for high-grade dysplasia, intramucosal cancer, and submucosal cancer and (2) immunoreactivity occurs late in the metaplasia-dysplasia-carcinoma sequence, during the transition to high-grade dysplasia. PMID- 7983882 TI - Evaluation of leukocyte-depleted terminal blood cardioplegic solution in patients undergoing elective and emergency coronary artery bypass grafting. AB - Leukocyte depletion at reperfusion may have a role in myocardial protection when combined with terminal cardioplegia. We applied this method in a selected group of 68 patients with coronary artery bypass grafting either for elective surgical procedures (n = 38) or emergency surgical procedures with the use of a preoperative intraaortic balloon pump (n = 30) because of developing acute myocardial infarction. Basic cold potassium crystalloid cardioplegic solution was used. During delivery of leukocyte-depleted terminal cardioplegic solution, warm arterial blood delivered from cardiopulmonary bypass was passed through a leukocyte removal filter, mixed with potassium crystalloid cardioplegic solution, and administered to the aortic root for the first 10 minutes of reperfusion. Patients were randomized into three groups for reperfusion: whole blood, terminal cardioplegic solution, and leukocyte-depleted terminal cardioplegic solution reperfusion groups. In elective coronary artery bypass grafting, no significant difference was found in the clinical data. However, in emergency coronary artery bypass grafting, the leukocyte-depleted terminal cardioplegic solution group (n = 10) showed significantly lower peak creatine kinase MB levels (leukocyte-depleted terminal cardioplegic solution versus terminal cardioplegic solution versus whole blood: 27 +/- 11, 56 +/- 13, 74 +/- 18, respectively; p < 0.05) and maximum dopamine doses required at the weaning of cardiopulmonary bypass (6.3 +/- 1.1 versus 11.2 +/- 3.3 versus 9.2 +/- 2.2; p < 0.05) than did the terminal cardioplegic solution (n = 10) and whole blood groups (n = 10). Moreover, the leukocyte-depleted terminal cardioplegic solution group showed significantly lower difference of malondialdehyde between arterial and coronary sinus blood (0.15 +/- 0.09 versus 0.36 +/- 0.06 versus 0.06 +/- 0.12 nmol/ml, p < 0.05) than did the terminal cardioplegic solution or whole blood groups. These results showed that leukocyte-depleted terminal blood cardioplegic solution may have a role in attenuating reperfusion injury in patients with critical conditions such as preoperative myocardial ischemic injury. PMID- 7983884 TI - Esophageal carcinoma. The unusual variants. AB - The clinical behavior and response to therapy of rare histologic variants of esophageal carcinoma are unclear. To evaluate the results of therapy in this group the records of 29 patients treated between 1949 and 1991 with primary rare histologic variants of esophageal carcinoma were retrospectively reviewed. This group represented 1.2% of 2454 cases of esophageal carcinoma treated between 1949 and 1991 and included mucoepidermoid (n = 14), small-cell (n = 12), adenoid cystic (n = 2), and carcinosarcoma (n = 1) carcinomas. Treatment for localized disease consisted of esophagectomy in five of seven patients with mucoepidermoid carcinoma, two of six patients with small-cell carcinoma, two of two patients with adenoid cystic carcinoma, and one of one patient with carcinosarcoma. Patients with stage IV mucoepidermoid carcinoma were treated predominately with radiation therapy (5/7). The majority of small cell carcinomas were treated with multiagent chemotherapy (10/12). The 1- and 3-year disease-specific survivals were 54% and 9% for mucoepidermoid carcinoma (median survival, 5 months) and 16% and 0% for small-cell carcinoma (median survival, 7 months), respectively. Patients with stage III mucoepidermoid carcinoma (median survival, 20.5 months) compared with those with stage III small-cell carcinoma (median survival, 6.2 months) had a significantly longer duration of survival (p < 0.05). Distant disease was present in 86% of patients in whom recurrence developed after esophagectomy Esophagectomy is standard therapy for localized carcinomas of the esophagus. Small-cell carcinoma appears to be a more aggressive variant of carcinoma and is most commonly treated with chemotherapy. PMID- 7983885 TI - Anomalous origin of the left coronary artery from the pulmonary artery. PMID- 7983886 TI - Platelet-rich plasmapheresis in cardiac surgery: efficacy may yet be demonstrated. PMID- 7983887 TI - Donor-recipient size match in heart transplantation. PMID- 7983888 TI - Use of microfibrillar collagen hemostat (Avitene) and thrombin to achieve hemostasis after median sternotomy. PMID- 7983889 TI - Respiratory syncytial virus infection in a cardiac surgery intensive care unit. PMID- 7983890 TI - Use of hyperpolarizing agents for induction of cardiac arrest during cardioplegia. PMID- 7983891 TI - Sequential internal mammary artery grafting. PMID- 7983892 TI - Chylothorax and wound lymphocele formation as a complication of myocardial revascularization with the internal thoracic artery. PMID- 7983893 TI - Chylothorax. PMID- 7983894 TI - Determination of positioning of coronary sinus cannula for retrograde cardioplegia with intraoperative myocardial contrast echocardiography. PMID- 7983895 TI - A simplified blood-perfused isolated heart preparation. PMID- 7983896 TI - Stabilization of the chest with absorbable cord after sternal resection. PMID- 7983897 TI - [Application of molecular epidemiology techniques in the study of food poisoning caused by Staphylococcus aureus]. AB - BACKGROUND: The use of molecular epidemiology techniques has provided better knowledge as to the clonal organization of bacterian populations and thus allows better follow up of epidemics. An alimentary toxiinfection in a Barcelona school produced by Staphylococcus aureus was analyzed by the combination of epidemiologic, phenotype and genotype markers with the aim of determining the source of the alimentary contamination. METHODS: Nine strains of Staphylococcus aureus isolated in 6 food manipulators and 3 patients were studied with the following markers: biotype, antibiotype, phagotype, plasmid profile, polymorphism of the size of the restriction fragments of total DNA and ribotype. RESULTS: Epidemiologic study of the strains analyzed showed that both the phenotype markers and the plasmid profile are thecniques of little discriminatory value. The only clearly discriminatory technique used was ribotyping which defined 3 clones in the 9 strains of Staphylococcus aureus studied. CONCLUSIONS: Molecular study of isolated strains of Staphylococcus aureus was able to identify the causal origin of the alimentary toxiinfection in one of the 6 food manipulators studied. PMID- 7983898 TI - [Risk factors of pregnancy in teenagers using family planning. Work Group on Sexuality and Adolescence]. AB - BACKGROUND: Pregnancy and maternity during adolescence constitutes an obstetric and perinatal risk factor and reason for increased social alarm. Nonetheless, the predisposing factors have been little studied in Spain. METHODS: The demographic data and information on the age of onset of sexual relations, contraceptive methods used, in addition to the reason for the first visit, corresponding to the users of six municipal family planning centers in Barcelona who were under the age of 20 years at the time of the first visit were analyzed. Likewise, the principal incidences in the follow up, including pregnancies, abortions and changes in contraceptive methods were collected. RESULTS: From October 1989 to September 1990 823 first visits corresponding to adolescents were registered. Forty-five percent (380) were under the age of 18 years with 716 (87%) having initiated full sexual relations with more than two years having passed prior to the first visit to the center in 183 cases (26%). The most frequent reason for the visit to the center was to request contraception (48%). The lack of labor and academic activity, in addition to the infrequent use of condoms were associated to pregnancy as the reason for the consultation in 42 cases. Twenty-four adolescents became pregnant during follow up being associated to the early initiation of sexual relations, with an interval of two or more years prior to attending the center and a change in contraceptive method. CONCLUSIONS: The delay in attending family planning centers and the use of little effective contraceptive methods are risk factors for undesired pregnancy in adolescence. PMID- 7983899 TI - [Usefulness of the breath test with urea-13C in the diagnosis of Helicobacter pylori infection]. AB - BACKGROUND: Many diagnostic methods of variable diagnostic profitability are available to detect infection by Helicobacter pylori. The aim of this study was to evaluate the usefulness of the European method of the breath test with urea 13C and compare the results with common histologic methods, the rapid urease test and serology. METHODS: Thirty-six patients who attended the Endoscopy Unit for recurrent symptomatology of the upper digestive tract were included in the study. A patient was considered to present infection by Helicobacter pylori on positivity of 2 of the usual methods: histology, rapid urease test and serology. RESULTS: The breath test with urea-13C was positive in 25 patients (13CO2 > 5 per 1,000) and negative in 10 patients with 100% specificity and 96% sensitivity. The specificity of the rapid urease test, histology and serologic tests were 90, 90 and 80%, respectively with 92, 88, and 88% sensitivity, respectively. CONCLUSIONS: The European method of the breath test with urea-13C is simple, non invasive and achieves the greatest profitability in the determination of Helicobacter pylori. PMID- 7983900 TI - [Acute non-cardiogenic lung edema associated with transfusion. An underestimated complication]. PMID- 7983901 TI - [A National Library of Health]. PMID- 7983902 TI - [Validity of intrathecal secretion formulas of IgG in the follow-up of the response to neurosyphilis treatment]. AB - The different formulas on intrathecal secretion of IgG were evaluated in patients with active neurosyphillis (NS) who did not have HIV infection with the aim of knowing their usefulness and sensitivity in the follow up of response to treatment. Five HIV negative patients with defined criteria of active NS were analyzed. The QAib ratio (albumin LCR/serum x 1,000) and Tourtellotte, Schuller and Reiber formulas of intrathecal secretion and the Link's index were studied prior to and at 15 days and three months following treatment with high intravenous doses of penicillin G over 12 days. A decrease in the QAlb ratio and all the formulas of intrathecal secretion of IgG was observed after treatment. The mean decrease was statistically significant on the third month after treatment for the Tourtellotte formula (116.6 +/- 44 mg/dl in basal control, 60.7 +/- 38 mg/dl at 15 days and 46.5 +/- 59 mg/dl at three months) (p < 0.05). The same evolutive pattern was not observed with the Link's index 1.75 +/- 9 mg/dl in basal control, 1.16 +/- 5 mg/dl at 15 days and 1.79 +/- 1 mg/dl at 3 months) in this series. The formulas of intrathecal secretion of IgG are useful to evaluate the response to treatment of patients with active neurosyphilis. The Tourtellotte formula was shown to be better than the Link index in this evaluation. PMID- 7983903 TI - [Cerebral toxoplasmosis with atypical presentation in a bone marrow transplant patient]. AB - The diagnosis of cerebral toxoplasmosis in an immunosuppressed patient is based on computer tomography (CT) findings and response to specific empiric treatment. Although infrequent, cerebral toxoplasmosis has been described in patients undergoing bone marrow transplantation (BMT) with lesions compatible with this diagnosis always being found on cranial CT. The case of a patient with Burkitt's lymphoma who received BMT and developed convulsive crisis with repeatedly normal cranial CT scans during the course of severe immunosuppression (graft versus host disease and treatment with 3 immunosuppressive drugs) is presented. Post mortem study demonstrated cerebral cysts of Toxoplasma gondii with slight perilesional inflammatory infiltrate. Normal CT in patients with neurologic foci and severe immunosuppression following BMT does not exclude the diagnosis of cerebral toxoplasmosis, therefore more sensitive diagnostic techniques should be performed, particularly in areas in which infection by toxoplasma is endemic. PMID- 7983904 TI - [Protocols for the prevention and treatment of thromboembolic disease (IV). Antithrombotic therapy in thromboembolism of the cranial vessels. The Editorial Committee on Protocols]. PMID- 7983905 TI - [Diarrhea, adenopathies, and pulmonary lesions in a 42-year-old male with common variable immunodeficiency]. PMID- 7983906 TI - [Prevalence of serologic markers of hepatitis B virus in non-hospital health personnel]. PMID- 7983907 TI - [Esophageal candidiasis and possible relationship with pernicious anemia]. PMID- 7983909 TI - [Trigeminal sensitive neuropathy associated with polymyositis]. PMID- 7983908 TI - [Staphylococcus bovis infective endocarditis associated with gastric adenocarcinoma]. PMID- 7983910 TI - [How to improve the vocational rehabilitation? A versatile expert group for the most difficult cases]. PMID- 7983911 TI - [Malnutrition--cause or effect?]. PMID- 7983912 TI - [Avoid mammoth surveys in dementia]. PMID- 7983913 TI - [Computer tomography in scanning of lungs in rheumatoid arthritis and methotrexate therapy]. PMID- 7983914 TI - [Bite analysis in tension headache]. PMID- 7983915 TI - [Antibodies against prolactin. A "new" cause of hyperprolactinemia]. PMID- 7983916 TI - [Current news on liver cancer. Difficult to express an opinion about cancer risk in hepatitis C]. PMID- 7983917 TI - [Violence might be predicted among the mentally ill. Patients with schizophrenia should receive an active care after discharge]. PMID- 7983918 TI - [Obstructive sleep apnea syndrome. Current literature on diagnostic methods]. PMID- 7983919 TI - [Time for a Swedish registry on diabetes]. PMID- 7983920 TI - [A case report. Malrotation with a high ileus in an adult]. PMID- 7983921 TI - [Ultrasound in acute scrotal pain. May testicular torsion be excluded by color Doppler?]. PMID- 7983922 TI - [Heterosexually transmitted HIV. 40 Swedish cases per year]. PMID- 7983923 TI - [The program for scientists from developing countries at the Karolinska Institute. New ideas were tested in a course on health systems]. PMID- 7983924 TI - [Do not scare--encourage! Everyday ethics made easier by with real examples]. PMID- 7983925 TI - [Fraud in cancer studies. More stringent control required. The risk of fraud is increased by commercialization]. PMID- 7983926 TI - [Decentralized continuing education. A successful course in the Southern health care region]. PMID- 7983927 TI - [Cost differences of the occupational health services. A comparative analysis of 2 Volvo companies]. PMID- 7983928 TI - [Neglected care of slow-healing wounds. Increased engagement of physicians is necessary]. PMID- 7983929 TI - [A study among teenagers in Falkenberg: frightening abuse of anabolic steroids]. PMID- 7983931 TI - [Drugs and economics in my perspective. II: Dishonest marketing is a cause of overtreatment]. PMID- 7983930 TI - [Insufficient disinfection in insertion of vascular catheters]. PMID- 7983932 TI - [The Pitea model is a flop considering the costs]. PMID- 7983933 TI - [Patients at nursing homes too have a right to medical care]. PMID- 7983934 TI - [Transfusion in surgery of malignant tumors? Keep routines with atraumatic surgery]. PMID- 7983935 TI - [Hormonal therapy in primary nocturnal enuresis? Enuresis alarms should be tested prior to use]. PMID- 7983936 TI - [Treatment and measures in enuresis. Several good reasons for active treatment]. PMID- 7983937 TI - [Vaccine allergy--does it exist? Type 1-reaction after vaccination of children is uncommon]. PMID- 7983938 TI - [A dreaded complication. Permanent loss of vision in temporal arteritis]. PMID- 7983939 TI - [Anticoagulants in non-valvular atrial fibrillation. A clinical dilemma in practice]. PMID- 7983940 TI - [Deficient knowledge of ventricular carcinoid. A new study will answer the question-marks]. PMID- 7983941 TI - [Teenagers in sparsely populated areas. Bad self image and many unhealthy symptoms]. PMID- 7983942 TI - [Risk of poliomyelitis transmission still exists. Complete poliomyelitis prevention is important]. PMID- 7983943 TI - [A topic for the international conference on population dynamics: women's rights to control their own life]. PMID- 7983944 TI - [Whose criteria will direct the health services? The hospital management must make the strategic choices]. PMID- 7983945 TI - [Continuous quality assurance at an emergency department. Marker diagnoses resulted in a useful method]. PMID- 7983946 TI - Research after death. PMID- 7983947 TI - Cost-of-illness studies: fact or fiction? PMID- 7983948 TI - Single-dose antibiotic treatment for travellers' diarrhoea. PMID- 7983949 TI - Escaping gas: immortality, deflation, and toxic dilation. PMID- 7983950 TI - The land mine crisis: a growing epidemic of mutilation. PMID- 7983951 TI - Prospective randomised trial of atrial versus ventricular pacing in sick-sinus syndrome. AB - In patients with sick-sinus syndrome, single-chamber atrial pacing has been reported, in retrospective studies, to be associated with lower frequencies of atrial fibrillation, thromboembolism, heart failure, and mortality than ventricular pacing; although single-chamber ventricular pacing is most commonly used. We did a prospective randomised trial in 225 consecutive patients (142 women, 83 men; mean age 76 years) with the sick-sinus syndrome, randomised to atrial (n = 110) or ventricular (n = 115) pacing and followed for up to 5 years (mean 40 [SD 18] months). During follow-up, the frequency of atrial fibrillation was higher in the ventricular group, except at the first follow-up at 3 months. Thromboembolic events (stroke or peripheral arterial embolus) occurred in 20 patients in the ventricular group and in 6 patients in the atrial group (p = 0.0083). 25 patients died in the ventricular group compared with 21 in the atrial group (p = 0.74). Heart failure estimated by the New York Heart Association classification and by the daily doses of diuretics did not differ between the two groups. Atrioventricular block occurred in 2 patients in the atrial group. Patients with sick-sinus syndrome should be treated with atrial pacing rather than ventricular pacing because atrial pacing is associated with lower frequencies of atrial fibrillation, thromboembolic complications, and a low risk of atrioventricular block. PMID- 7983952 TI - Sun exposure and melanocytic naevi in young Australian children. AB - Queensland, Australia, has the highest rates of melanoma in the world and Queensland children have the greatest numbers of melanocytic naevi, the strongest risk factor for melanoma. Although both melanoma and naevi are broadly related to sun exposure in childhood, the relation to individual exposure early in life is difficult to study retrospectively in adults. We surveyed 506 children aged 1-6 years who had been born in Townsville, North Queensland. Sun exposure was assessed by questionnaire and melanocytic naevi were counted using a standard international protocol. Very high counts (upper quarter) of melanocytic naevi were significantly associated with sun exposure of more than 4 hours per day (adjusted relative risk ratio 3.29; 95% Cl 1.12-9.69), and with a history of sunburn (1.89; 1.11-3.21). Melanocytic naevus counts increased with age, light skin reflectance, and freckling. With exposure to intense ultraviolet light in Townsville, children develop melanocytic naevi early in life and in large numbers. We found that both acute and chronic exposure to sun are associated with their development. PMID- 7983953 TI - Prevalence of metaplasia at the gastro-oesophageal junction. AB - Specialised columnar epithelium (SCE), a form of intestinal metaplasia usually found in Barrett's oesophagus, cannot be distinguished endoscopically from normal gastric epithelium. Endoscopists seldom obtain biopsy specimens from a normal appearing gastro-oesophageal junction, and therefore short segments of SCE in this region may go unrecognised. We studied patients who had short segments of SCE at the gastro-oesophageal junction. All patients scheduled for elective endoscopic examinations in our general endoscopy unit, irrespective of indication, were questioned for symptoms of gastro-oesophageal reflux disease. At endoscopy, severity of oesophagitis was graded, and biopsy specimens obtained from the squamocolumnar junction, irrespective of its appearance or location in the oesophagus. Among 142 patients without endoscopically apparent Barrett's oesophagus, 26 (18%) were found to have SCE. All patients with SCE were white, and the male/female ratio was 1.9. In contrast, non-whites accounted for 14% of the 114 patients without SCE and the male/female ratio was 0.8. The groups did not differ significantly in the frequency of symptoms and endoscopic signs of gastrooesophageal reflux. We conclude that adults frequently have unrecognised segments of SCE at the gastro-oesophageal junction; this may underlie the rising frequency of cancer of the gastrooesophageal junction in the USA and Europe. PMID- 7983954 TI - Randomised trial of single-dose ciprofloxacin for travellers' diarrhoea. AB - Diarrhoea is the most common illness affecting travellers to developing countries. Our study was designed to compare the efficacy of a single 500 mg dose of ciprofloxacin with placebo for treatment of acute diarrhoea in travellers. British troops who were within their first 8 weeks of deployment in Belize and who presented within 24 h of the onset of diarrhoea, were randomized to receive either ciprofloxacin 500 mg or placebo. Every subject recorded the number and consistency of stools and presence of any other associated symptoms for 72 h or until recovery. Of 88 subjects enrolled, 83 were evaluable, of whom 45 received ciprofloxacin and 38 placebo. Groups did not differ with regard to duration or severity of diarrhoea at randomisation. Mean (SE) duration of diarrhoea, as assessed by time to the last liquid and last unformed stool, was reduced from 50.4 (4.5) h and 53.5 (4.4) h, respectively, in the placebo group to 20.9 (3.4) h and 24.8 (3.8) h in those receiving ciprofloxacin (p < 0.0001). Mean number of liquid stools was reduced from 11.4 (1.2) in the placebo group to 5.0 (0.7) in the ciprofloxacin-treated group (p < 0.0001). The cumulative percentages of subjects with no unformed stool after 24 h, 48 h, and 72 h were, respectively, 64%, 82%, and 93% in the ciprofloxacin group and 11%, 42%, and 79% in the placebo group (p < 0.0001, p < 0.001, and not significant, respectively). A single 500 mg dose of ciprofloxacin was an effective empirical treatment for reducing the duration and severity of diarrhoea in travellers. The regimen should maximise compliance and reduce the cost and duration of therapy. PMID- 7983955 TI - Cellular immune response to common mycobacterial antigens in subjects seropositive for Trypanosoma cruzi. AB - The immune response is impaired in the silent stage of Chagas' disease. We used quadruple skin-testing with new tuberculins in 37 adults who were symptom-free but seropositive for Trypanosoma cruzi and in 37 matched seronegative controls. Whereas 19% of controls responded to common mycobacterial antigens, none of the Chagas' seropositive group responded to them (p < 0.006), demonstrating specificity in their unresponsiveness. The enhanced tuberculin reactivity after BCG vaccination in the control group was suppressed in seropositive subjects (p < 0.002). Selective loss of response to common mycobacterial antigens may have implications for the autoimmune pathology of Chagas' disease, and for susceptibility to tuberculosis, leprosy, and HIV disease. PMID- 7983956 TI - Treatment of exudative fibrinous pericarditis with intrapericardial urokinase. AB - Three male patients with purulent pericarditis, in whom complete drainage could not be obtained by pericardiocentesis, were treated with transcatheter intrapericardial urokinase to prevent the development of chronic constrictive pericarditis. As shown by echocardiography, the intrapericardial fibrin layers disappeared in two cases and were reduced by more than half in the third. Effects on systemic coagulation indices and complications related to intrapericardial lysis were not observed. PMID- 7983957 TI - Clinical data systems, Part 1: Data and medical records. PMID- 7983958 TI - Antimicrobial prophylaxis in neurosurgery and after head injury. Infection in Neurosurgery Working Party of the British Society for Antimicrobial Chemotherapy. PMID- 7983959 TI - Clinical trials with ambulatory blood pressure monitoring: fewer patients needed? Syst-Eur Investigators. AB - We have tested the concept that fewer patients are needed in trials of antihypertensive treatment if blood pressure is measured by ambulatory monitoring rather than by conventional sphygmomanometry. 233 patients (> or = 60 years old) with isolated systolic hypertension were randomly allocated placebo (n = 119) or active treatment (n = 114). Blood pressure measurements were compared by Wilcoxon's test and blood pressure profiles by ANOVA. With either method of measurement, the same number of patients (40 in each treatment group) was required to show a reduction after 1 year in clinic (13/8 mm Hg) or average blood pressure over 24 h (9/5 mm Hg). To detect that the decrease in systolic pressure was not steadily maintained through the day, 40 patients in each treatment group were needed for blood pressure profiles made up of 4-hourly or 2-hourly means and 60 for profiles of 1-hourly means. For diastolic pressure, the corresponding numbers were 80, 100, and more than the number of available patients, respectively. We conclude that parallel-group trials focusing on the average blood pressure over 24 h, rather than on conventionally measured blood pressure, cannot economise on sample size. Moreover, trials studying the full course of blood pressure throughout the day, require more--not fewer--patients than studies of only the conventional or average 24 h blood pressure. PMID- 7983960 TI - Cardiologists rebuked. PMID- 7983961 TI - Hospital mortality league tables. PMID- 7983962 TI - Russia's law on iatrogenic HIV infection. PMID- 7983963 TI - Three cases of hepatocellular carcinoma among cyproterone users. Ad hoc Committee on Androcur Users. PMID- 7983964 TI - Liver tumours in women on oral contraceptives. PMID- 7983965 TI - Progressive renal failure in two breast cancer patients after high-dose ifosfamide. PMID- 7983966 TI - Gastroenteritis associated with Helicobacter pullorum. PMID- 7983967 TI - Mechanism of anti-inflammatory action of retinoids on keratinocytes. PMID- 7983968 TI - Neonatal listeriosis in twins due to cross-infection in theatre recovery room. PMID- 7983969 TI - Differences in heterosexual transmission of HIV-1 and HIV-2. PMID- 7983970 TI - Nocturnal change of heart rate and diurnal blood pressure rhythm. PMID- 7983971 TI - Cost of coronary angioplasty versus coronary artery bypass surgery. PMID- 7983972 TI - Polio outbreaks: a tale of torment. PMID- 7983973 TI - Pertussis vaccination. PMID- 7983974 TI - Information preferences of patients with cancer. PMID- 7983976 TI - Longlasting improvement of Tourette's syndrome with transdermal nicotine. PMID- 7983975 TI - Tumour stimulating effects of recombinant human interleukin-6. PMID- 7983977 TI - Prevention of neural tube defects. PMID- 7983978 TI - Mortality in epilepsy. PMID- 7983979 TI - Mortality in epilepsy. PMID- 7983980 TI - Mortality in epilepsy. PMID- 7983981 TI - Is it possible to catch leukaemia from a cat? PMID- 7983982 TI - Vitamin D receptor genotypes in osteoporosis. PMID- 7983984 TI - Onchocerca volvulus and Schistosoma haematobium infection in southern Sierra Leone. PMID- 7983983 TI - Vitamin D receptor genotypes in osteoporosis. PMID- 7983985 TI - Laparoscopic surgery. PMID- 7983986 TI - Surveillance of ampullary adenomas in familial adenomatous polyposis. PMID- 7983987 TI - Burnished or burnt out: the delights and dangers of working in health. PMID- 7983988 TI - Epilepsy, cerebral calcifications, and coeliac disease. PMID- 7983989 TI - Cardiovascular disease epidemiology in developing countries: ethics and etiquette. PMID- 7983990 TI - Backing off universal childhood lead screening in the USA: opportunity or pitfall? PMID- 7983991 TI - Herbis et orbis: the dangers of traditional eye medicines. PMID- 7983992 TI - Maternal mild hyperphenylalaninaemia: an international survey of offspring outcome. AB - Maternal phenylketonuria (PKU) has adverse effects on the offspring including microcephaly, mental retardation, congenital heart disease, and intrauterine growth retardation. Maternal non-PKU mild hyperphenylalaninaemia (MHP) is believed to be benign, but whether there may be long-term consequences to offspring is unclear. In an international survey we have obtained information about 86 mothers with MHP (blood phenylalanine 167-715 mumol/L), their 219 untreated pregnancies, and 173 offspring. Spontaneous fetal loss (13% of pregnancies), congenital heart disease (2.3% of offspring), and severe non cardiac anomalies (2.9% of offspring) occurred at frequencies within expected limits for the general population. For weight and length at birth the median percentile was the 50th but that for birth head circumference was the 25th. Median z-scores for birth length and head circumference were significantly lower for offspring of mothers with phenylalanine concentrations above 400 mumol/L than for those whose mothers had lower values (p = 0.05 and p = 0.005, respectively). The median intelligence quotient (IQ) of the offspring (3-27 years) was 100 for those whose mothers had higher phenylalanine concentrations and 108 for those of the lower phenylalaninaemia group. However, offspring IQ correlated slightly more closely with maternal IQ (r = 0.53, p < 0.001) than with maternal phenylalanine concentration (r = 0.45, p = 0.02). Maternal MHP does not seem to have serious consequences for the fetus. A maternal phenylalanine concentration of less than 400 mumol/L does not warrant intervention. Nevertheless, maternal blood phenylalanine above this value is associated with slightly lower birth measurements and offspring IQ than lower maternal blood phenylalanine concentrations. PMID- 7983993 TI - Amphotericin versus sodium stibogluconate in first-line treatment of Indian kala azar. AB - Patients do not always respond to treatment of visceral leishmaniasis with pentavalent antimony, and the drug has toxic effects. Amphotericin B might be useful as an alternative first-line treatment for the disease. We compared the efficacy of amphotericin and sodium stibogluconate in a prospective randomised trial in 80 uncomplicated and parasitologically confirmed cases of Indian kala azar. None of the patients had received an antileishmanial agent before. Sodium stibogluconate was given at 20 mg/kg in two divided doses daily for 40 days, and amphotericin in fourteen doses of 0.5 mg/kg infused in 5% dextrose on alternate days. All 40 patients randomised to amphotericin were cured; of the 40 patients assigned to sodium stibogluconate, 28 (70%) showed initial cure and 25 (62.5%) showed definitive cure (p < 0.001). With amphotericin, there was quicker abatement of fever and more complete spleen regression with no serious adverse effects. Amphotericin is effective in the first-line treatment of Indian kala azar and superior to antimony therapy. PMID- 7983994 TI - Is evidence for homoeopathy reproducible? AB - We tested, under independent conditions, the reproducibility of evidence from two previous trials that homoeopathy differs from placebo. The test model was again homoeopathic immunotherapy. 28 patients with allergic asthma, most of them sensitive to house-dust mite, were randomly allocated to receive either oral homoeopathic immunotherapy to their principal allergen or identical placebo. The test treatments were given as a complement to their unaltered conventional care. A daily visual analogue scale of overall symptom intensity was the outcome measure. A difference in visual analogue score in favour of homoeopathic immunotherapy appeared within one week of starting treatment and persisted for up to 8 weeks (p = 0.003). There were similar trends in respiratory function and bronchial reactivity tests. A meta-analysis of all three trials strengthened the evidence that homoeopathy does more than placebo (p = 0.0004). Is the reproducibility of evidence in favour of homoeopathy proof of its activity or proof of the clinical trial's capacity to produce false-positive results? PMID- 7983996 TI - Clinical data systems, Part 2: Components and techniques. PMID- 7983995 TI - Incidence of familial melanoma and MLM2 gene. AB - The overall incidence of melanoma is increasing world wide. We investigated whether there has been an increase in familial melanoma by studying age at onset among different birth cohorts in 18 melanoma kindreds linked to a predisposition gene (MLM2) on chromosome 9. The cumulative incidence of melanoma was 21-fold higher (95% CI 5.2-84.6) among subjects born after 1959 than in those born before 1900. The expected age of onset of the group born after 1959 was 24 years earlier (21.0 vs 45.0 years). These data support the notion that phenotypic penetrance of the MLM2 gene is increasing, presumably as a result of the interaction of sunlight exposure and mutation at this locus. PMID- 7983997 TI - Acute promyelocytic leukaemia. Report of a meeting of Physicians and Scientists, University College London. PMID- 7983998 TI - Three-dimensional video-endoscopy: clinical use in gynaecological laparoscopy. AB - We describe a system that displays the abdominal organs in three dimensions during laparoscopy. The system consists of a single-rod-lens endoscope and two integrated microchip cameras. The surgeon has to wear active-liquid-crystal shutter-glasses to obtain a three-dimensional impression during the operation. Improved orientation in the abdominal cavity allows exact handling of surgical instruments. The three-dimensional system permits surgery with more accuracy, speed, dexterity, and safety than conventional two-dimensional systems. PMID- 7983999 TI - Migraine in doctors: work loss and consumption of medication. PMID- 7984000 TI - New politics of tobacco favours industry. PMID- 7984001 TI - Paris AIDS summit. PMID- 7984003 TI - First 5 years of gene therapy for cancer. PMID- 7984002 TI - World Bank warns of AIDS economic threat. PMID- 7984004 TI - Patent rights and HCV tests. PMID- 7984005 TI - Cohabitation and pregnancy-induced hypertension. PMID- 7984006 TI - Cohabitation and pregnancy-induced hypertension. PMID- 7984007 TI - Cohabitation and pregnancy-induced hypertension. PMID- 7984008 TI - Cohabitation and pregnancy induced hypertension. PMID- 7984009 TI - Dobutamine-atropine stress echocardiography and central anticholinergic syndrome. PMID- 7984010 TI - Isolation of pathogenic hantavirus from white-footed mouse (Peromyscus leucopus) PMID- 7984011 TI - Dangers of bismuth iodoform paraffin paste. PMID- 7984012 TI - Epidemic malaria in India and the El Nino southern oscillation. PMID- 7984013 TI - Influence of ancestral gender on transmission of familial amyotrophic lateral sclerosis. PMID- 7984014 TI - Vaccination against asthma. PMID- 7984015 TI - Treatment for drug dependence. PMID- 7984016 TI - Standards for information systems in the global health network. PMID- 7984018 TI - Placebos in medicine. PMID- 7984017 TI - Medical future for Hong Kong. PMID- 7984019 TI - Reconciliation for Rwanda's children. PMID- 7984020 TI - Placebos in medicine. PMID- 7984021 TI - Placebos in medicine. PMID- 7984022 TI - Placebos in medicine. PMID- 7984024 TI - Pregnancy and prosthetic heart valves. PMID- 7984023 TI - Recurrence rate of oesophageal varices with endoscopic banding ligation followed by injection sclerotherapy. PMID- 7984025 TI - Pregnancy and prosthetic heart valves. PMID- 7984026 TI - Metastatic squamous cell cancer after psoralen photochemotherapy. PMID- 7984027 TI - Emergency endovascular repair of leaking aortic aneurysm. PMID- 7984029 TI - Cardioversion of fetal tachyarrhythmia with adenosine. PMID- 7984028 TI - Parity and Down's syndrome. PMID- 7984030 TI - Encephalopathy with seizures after use of aluminium-containing bone cement. PMID- 7984031 TI - Diabetes and the thrifty gene. PMID- 7984032 TI - Molecular mechanisms of action of bacterial protein toxins. PMID- 7984033 TI - Localization and age-dependent expression of hexokinase mRNA in the rat brain. AB - Localization of mRNA encoding for the enzyme hexokinase and its regulation in aged animals was carried out in rat brain using the in situ hybridization technique. The highest levels of the hybridization signal were observed in the olfactory bulb, piriform cortex, tenia tecta, hippocampus and granular cells of the cerebellum. Other brain areas and nuclei including cerebral cortex, thalamus, hypothalamus, substantia nigra, subiculum, choroid plexus and superior colliculus displayed moderate to low density of transcripts. Correlation between relative hexokinase content and levels of its mRNA was found only for some brain regions such as caudate-putamen, geniculate nucleus, ventral and lateral thalamic nuclei, superior colliculus and granular cells of the cerebellum. In the cerebral cortex and hippocampus of old animals the expression of hexokinase was significantly increased at 18 and 24 months of age. From the present data we conclude that although hexokinase is an ubiquitous enzyme, sites of synthesis display a discrete and uneven localization in rat CNS and expression, in the aging brain, might be regulated to compensate for reduced oxidative phosphorylation in the brain tissue. PMID- 7984034 TI - L-carnitine uptake into primary rat cortical cultures: interaction with GABA. AB - The ability of the primary rat cortical cells to take up L-carnitine increased with the age of the cultures and plateaued at around day 11 up to 25 days in vitro (DIV) when a slight decline was evident and by 32 DIV there was a major decrease in L-carnitine uptake. The uptake of L-carnitine displayed complex components. Elimination of mitochondrial energy supply by NaCN (1 mM), rotenone (1.25 microM) and DNP (50 microM), caused a small but significant decrease in the uptake (21, 11 and 16%, respectively). The uptake was highly dependent on the Na gradient, since ouabain (0.5 mM) and Na free buffer (replaced by 250 mM sucrose), reduced uptake by 54 and 63%, respectively. There was competition of L-carnitine uptake by molecules resembling its structure, e.g. gamma-aminobutyric acid (GABA), acetyl-L-carnitine (ALC), D-carnitine, L-aminocarnitine and L-choline, with GABA being the most potent inhibitor (57% at 50 microM) and L-choline not being significantly active. The Na-dependent uptake of L-carnitine was saturable with a high Km (692 microM) and Vmax (839 pmol/min/mg). This Na-dependent component was not further additive with the GABA (500 microM) or the DNP (50 microM) inhibitable component, suggesting that it represented the same phenomenon, probably the Na gradient dependent transport of L-carnitine. The results indicate that the uptake of L-carnitine occurs by Na-dependent saturable process as well as non-saturable, Na-independent processes. At least the former uptake mechanism is potently inhibited by GABA. PMID- 7984035 TI - Molecular cloning of rat cDNAs for the zeta and theta subtypes of 14-3-3 protein and differential distributions of their mRNAs in the brain. AB - We isolated from the rat brain two cDNA clones encoding the zeta and theta subtypes of the 14-3-3 protein. Both clones encoded 245 amino acid sequences, which share a high sequence homology with each other and also with other subtypes of the 14-3-3 protein. The distribution of their mRNAs was determined in the developing brain, by in situ hybridization with subtype-specific oligonucleotide probes. At embryonic day 18, the zeta and theta subtype mRNAs were expressed at high levels throughout the brain and the spinal cord. Distribution patterns of the two mRNAs were distinct in the brain at postnatal day 21. The zeta subtype mRNA was distributed widely in the brain gray matter, and high levels of the transcripts were detected in various brain regions, including the neocortex, hippocampus, caudate-putamen, thalamus, cerebellar cortex, and several brainstem nuclei. On the other hand, high signal levels of the theta subtype mRNA in the gray matter were restricted to the cerebellar cortex and the hippocampus. In addition, significant signals for the theta subtype mRNA were found over the white matter, where cell bodies of glial cells are populated. The wide gene expression of the zeta and theta subtypes suggests their fundamental and essential role in the brain function, but the degrees of functional involvement by the respective subtypes would be heterogeneous between neuron and glia, and also among neuron types. PMID- 7984037 TI - Drastic and selective hyperinnervation of central serotonergic neurons in a lethal neurodevelopmental mouse mutant, Anorexia (anx). AB - The autosomal recessive lethal anorexia mutation in mice (anx/anx) causes starvation in preweanlings. In addition, this murine neurodevelopmental mutant shows other distinct phenotypic characteristics and dysfunctional behaviors. Previous studies strongly suggested that the mutation results in elevated serotonergic stimulation, because these traits are characteristic of such overstimulation and because brain serotonin is believed to have an inhibitory effect on feeding behavior. In this report, we show extensive serotonergic hyperinnervation in normal target fields (hippocampus, cortex, olfactory bulb and cerebellum) of mutant mice. Despite the extensive hyperinnervation, the normal laminar organization of the brain was retained. The specificity of the mutation to the serotonergic system was confirmed by demonstration of normal catecholaminergic innervation in the central nervous system (CNS), and this specificity was especially striking in a common target field, the cerebellum. Serotonergic hyperinnervation in these mutant preweanling mice may represent the underlying etiology of increased serotonergic stimulation which leads to anorexic starvation, abnormal behavior, and premature death. PMID- 7984036 TI - Cellular distribution of nicotinic acetylcholine receptor subunit mRNAs in the human cerebral cortex as revealed by non-isotopic in situ hybridization. AB - The pharmacology of telencephalic nicotinic acetylcholine receptors (nAChRs) has become an important issue in recent years. While in the human brain a direct pharmacological assessment is difficult to achieve the visualization of nAChRs has been enabled by histochemical techniques providing an ever increasing and improving resolution. Receptor autoradiography was used to visualize binding sites on the level of cortical layers whereas immunohistochemistry has allowed for the cell type-specific and ultrastructural localization of receptor protein. Further investigations have to elucidate the cellular sites of NAChR biosynthesis by visualizing subunit-specific transcripts. Using autopsy samples of the human precentral cortex (Area 4) as a paradigm we have applied digoxigenin-labeled cRNA probes to localize transcripts for the alpha 3- and alpha 4-1-subunits of the nAChR. In accordance with findings in the monkey cortex, the alpha 3-subunit seems to be expressed mainly in pyramidal neurons of layers III-VI of the human cerebral cortex. Transcripts for the alpha 4-1-subunit, by contrast, appear to be present in a large number of neurons throughout all layers of the cerebral cortex, consonant with its ubiquitous distribution in the rodent brain. The present findings show that also in human autopsy brains the cell type-specific detection of nAChR transcripts is possible. For the future, this technique will enable to investigate the expression of receptor transcripts in diseased human brains as compared to controls. PMID- 7984038 TI - Identification of carboxypeptidase H transcripts by antisense RNA. AB - Carboxypeptidase H is a metallopeptidase involved in the processing of neuropeptide precursors and prohormones. In this study, northern analysis with antisense CPH RNA as probe detected the presence of three CPH mRNA transcripts of 2.2, 2.6, and 5.9 kb that are expressed in a tissue-specific manner in several species. Specifically, mouse brain and the mouse AtT-20 corticotroph cell line possess all three transcripts, but mouse pituitary and adrenal possess the 2.2 kb CPH mRNA as the main form. In bovine, the 5.9 kb CPH mRNA was detected in adrenal medulla, but not in pituitary; whereas, both of these bovine tissues possess the 2.2 kb form. Also, in rat brain, adrenal, heart, and pituitary, the 5.9 m,kb form was detected mainly in brain, and the 2.6 kb form was most abundant in pituitary; all rat tissues examined possessed the 2.2 kb form. Additional evidence for the existence of the largest CPH transcript was provided from a bovine adrenal medulla cDNA library by in vitro transcription of total library phage DNA, followed by analysis of resultant RNAs by Northern blot. It will be important in future studies to define the structural similarities and differences among these multiple CPH mRNA transcripts that are expressed in a tissue-specific manner. PMID- 7984039 TI - Dietary calcium deficiency causes a reduction in calretinin mRNA in the substantia nigra compacta-ventral tegmental area of rat brain. AB - Dietary calcium deprivation (3 weeks) affected neuronal gene expression of calretinin. Calcium deprived rats exhibited calcium appetite, weight loss, and a 28% decrease in calretinin mRNA in the substantia nigra compacta-ventral tegmental area, compared to controls. No changes were detected in 2 other mRNAs (tyrosine hydroxylase, beta-actin) and 5 other brain regions examined. This region-specific reduction of calretinin mRNA may relate to the altered physiology or behavior. PMID- 7984040 TI - Somatostatin receptors coupled to the inhibition of adenylyl cyclase in the rat frontoparietal cortex are modulated by alpha 2 adrenoceptors. AB - The administration of an alpha 2-adrenoceptor agonist, clonidine, increased the number of somatostatin (SS) receptors and the affinity constant in frontoparietal cortex membranes. In addition, in the clonidine group, the capacity of SS to inhibit basal and forskolin (FK)-stimulated adenylyl cyclase (AC) activity in the frontoparietal cortex was significantly higher than in the control group. Pretreatment with the alpha 2-adrenoceptor antagonist yohimbine prevented the clonidine-induced changes in SS binding and SS-inhibited AC activity. Yohimbine alone had an opposite effect from clonidine. These experiments provide further evidence that the alpha-adrenergic system modulates the rat frontoparietal cortex somatostatinergic system. PMID- 7984041 TI - Induction of c-fos gene expression is not responsible for increased proenkephalin mRNA levels in the hippocampal dentate gyrus following NMDA stimulation. AB - The increased levels of proenkephalin mRNA in the dentate gyrus following hippocampal stimulation have been assumed to be a consequence of the transient induction of c-fos. Injection of 50 microM NMDA in vivo onto the dendrites of a small number of granule cells causes a pronounced but highly localised elevation in proenkephalin mRNA levels 24 h later, whereas vehicle has no effect. In contrast, there is a widespread induction of c-fos mRNA throughout the dentate gyrus, 45 min after injection of either vehicle or NMDA, suggesting that induction of c-fos expression is unrelated to the subsequent, anatomically discrete, increase in proenkephalin mRNA levels. PMID- 7984042 TI - c-fos mRNA in the suprachiasmatic nuclei in vitro shows a circadian rhythm and responds to a serotonergic agonist. AB - The mammalian suprachiasmatic nuclei (SCN) contain a circadian clock that produces approximately 24 h rhythms of physiology and behavior even during constant dark. Under such conditions, light stimuli applied during the subjective night induce phase shifts of circadian rhythms and increase immediate early gene expression (c-fos) in the SCN. In vitro preparations of the SCN continue to show circadian rhythms of metabolic rate and neuronal firing rates, which can be phase shifted by non-photic stimuli. This study was designed to investigate whether the SCN display a rhythm of c-fos mRNA levels in vitro and whether quipazine, which phase-shifts the SCN circadian clock, induces c-fos expression in vitro. Levels of c-fos mRNA were found to be significantly higher in the subjective day than subjective night in the SCN in vitro. This rhythm parallels other in vivo and in vitro rhythms in SCN metabolic and neuronal activity and is consistent with previous in vivo work showing higher daytime levels of Fos-like immunoreactivity in animals maintained under constant dark conditions. Quipazine treatment during the subjective day (which phase-advances the circadian rhythm of neuronal firing in the SCN) decreased c-fos mRNA levels in the dorsomedial but not ventrolateral SCN, but quipazine did not affect c-fos levels when administered at night. This effect is consistent with serotonergic agonists inhibiting SCN neuronal activity and is the first evidence that a non-photic phase-shifting stimulus alters c-fos in the SCN at a phase-appropriate time. PMID- 7984043 TI - Gene regulation during neuronal and non-neuronal differentiation of NTERA2 human teratocarcinoma-derived stem cells. AB - We constructed cDNA libraries from a clonal human teratocarcinoma-derived cell line and two retinoic acid-induced derivatives: a homogeneous population of neurons and a FACS-isolated, non-neuronal population. These libraries are large and representative of the cells from which they were derived, as determined by colony hybridization. PCR analysis indicates that the transcripts encoding P- and E-cadherin are down-regulated whereas the the prion protein (PrP) transcript is up-regulated in neurons. These cells offer a promising system for investigations of human prion infection and the cDNA libraries provide a source of neuron specific genes. PMID- 7984045 TI - Differential induction of Fos protein and a Fos-related antigen following acute and repeated cocaine administration. AB - The present study examined the effects of a single and five once daily injections of cocaine on the expression of c-fos mRNA, Fos protein and Fos-related antigens (Fra) in the striatum. A single injection (40 mg/kg, i.p.), which induces locomotion, increased the expression of c-fos mRNA, Fos protein and a 35 kDa Fra. In contrast, five injections (40 mg/kg, i.p.) given once a day, which induces even more behavioral stimulation, diminished the increase in c-fos mRNA and Fos protein expression. However, the cocaine-induced Fra expression was sustained and not reduced after the five injections. The results demonstrate that cocaine induced expression of the Fos/Fra gene family is dynamic and the profile of gene transcription and translation in the striatum changes when animals are behaviorally more sensitive to cocaine. PMID- 7984044 TI - Expression and localization of gamma-aminobutyric acid A (GABAA) receptor alpha 1 subunit and L-glutamate decarboxylase (GAD) mRNAs in rat retina: an analysis by in situ hybridization. AB - The localization of the mRNAs encoding gamma-aminobutyric acidA receptor alpha 1 subunit (GABAA alpha 1) and L-glutamate decarboxylase (GAD) was elucidated in the rat retina by in situ hybridization. Soma diameter analysis of signal positive cells in the ganglion cell layer demonstrated that a subpopulation including alpha-cells of retinal ganglion cells expressed GABAA alpha 1 mRNA and a subpopulation of ganglion cells smaller than alpha-cells expressed GAD mRNA. PMID- 7984046 TI - The abundance of mRNA for dopamine D2 receptor isoforms in brain tissue from controls and schizophrenics. AB - The possibility that schizophrenia is associated with a differential expression, in the brain, of the short and long isoforms of the dopamine D2 receptor has been investigated by assessing the abundance of mRNA for each of the isoforms. Using a quantitative RNA-PCR technique, increased mRNA for both isoforms of the D2 receptor were observed in some brain regions, with no differential distribution between the isoforms in the schizophrenics compared to controls. PMID- 7984049 TI - Repeated administration of MDMA down-regulates preprocholecystokinin mRNA expression but not tyrosine hydroxylase mRNA expression in neurones of the rat substantia nigra. AB - The effect of repeated administration of 3,4-methylenedioxymethamphetamine (MDMA) on the expression of tyrosine hydroxylase and preprocholecystokinin (CCK) messenger RNAs in substantia nigra was examined by in situ hybridisation histochemistry. Sections hybridised with 35S-labelled oligonucleotides were subjected to computerised image analysis to determine the density of silver grains above positively labelled cells as an index of steady state mRNA levels. In the substantia nigra pars compacta, CCK mRNA levels were significantly reduced in drug-treated animals 24 h and at 2 weeks after the last dose of MDMA (10 mg/kg i.p., twice daily for 4 days). In the same animals, MDMA caused no change in the level of tyrosine hydroxylase mRNA in this brain region. The results show that MDMA can produce changes in dopamine neurones. Furthermore, since tyrosine hydroxylase and cholecystokinin are co-expressed in substantia nigra pars compacta, these results suggest that the expression of the tyrosine hydroxylase and CCK genes are regulated independently. PMID- 7984047 TI - Expression of basic-helix-loop-helix transcription factor ME2 during brain development and in the regions of neuronal plasticity in the adult brain. AB - We report the isolation of a cDNA encoding the mouse class A bHLH transcription factor ME2 and the analysis of its expression. ME2 is expressed in the cerebral cortex, Purkinje and granule cell layers of the cerebellum, olfactory neuroepithelium, pyramidal cells of hippocampal layers CA1-CA4, and in the granular cells of the dentate gyrus. The specific expression of ME2 during development and in the regions of neuronal plasticity in the adult brain suggest that ME2 may have a regulatory function in developmental processes as well as during neuronal plasticity. PMID- 7984048 TI - Immediate-early gene protein expression in neurons undergoing delayed death, but not necrosis, following hypoxic-ischaemic injury to the young rat brain. AB - A unilateral hypoxia-ischaemia (HI) 21-day-old rat preparation was used to assess the effects of HI on the expression of the immediate-early gene proteins (IEGPs) c-Fos/FRAs, Fos B, c-Jun, Jun B, Jun D, Krox 20, Krox 24, and on the mRNA for the neurotrophic factor, brain-derived neurotrophic factor (BDNF). Moderate HI (15 min hypoxia) produced delayed, selective neuronal death and was associated with a rapid induction of c-Fos, Fos B, Jun B, Jun D, and c-Jun proteins, but not Krox 20 protein or BDNF mRNA, in neurons on the side of HI and also a delayed expression of c-Jun (and to a lesser extent c-Fos/FRA's and Fos B) 24-48 h after HI in neurons that underwent delayed neuronal death. Krox 24 showed an initial induction followed by a long-lasting suppression of its expression in regions undergoing cell loss. Severe HI (60 min hypoxia) resulted in seizures and rapid neuronal loss and infarction (necrotic cell death) on the side of HI, and was associated with early induction of c-Fos, Fos B, c-Jun, Jun B, Jun D, Krox 20 and Krox 24 protein and BDNF mRNA in neurons on the non-ligated side of the brain. Fos, c-Jun, Jun B, Jun D and Krox 24, but not Krox 20, Fos B, or BDNF mRNA, were also induced in non-nerve cells on the damaged side of the brain after both moderate and severe HI, and many of these cells appeared to be dividing. Thus, moderate HI induces IEGP's in neurons and non-nerve cells in damaged regions, whereas severe HI induces IEGP's and BDNF in non-damaged regions. c-Jun (and to a lesser extent c-Fos/FRA's) showed a prolonged expression in neurons undergoing delayed, but not necrotic, cell death suggesting that they may be involved in the biochemical cascade that causes selective delayed neuronal death. BDNF was not induced by HI, and therefore, does not appear to play an endogenous neuroprotective role in the CNS. PMID- 7984050 TI - Upregulation of the pro-opiomelanocortin gene in motoneurons after nerve section in mice. AB - In the normal adult mouse a few of the ventral horn motoneurones were slightly immunoreactive for the pro-opiomelanocortin (POMC)-derived peptides beta endorphin (beta-EP) and alpha-melanotropin (alpha-MSH). After unilateral section of the sciatic nerve the incidence of immunoreactive cells and the intensity of staining increased in both the ipsilateral and the contralateral ventral horns. The proportion of cells which expressed the peptides reached a maximum at approximately 24 h after nerve section, and thereafter declined, but the proportion was still higher than normal at 7 days after the section. Using histochemical in situ hybridization with cDNA oligonucleotide probes for POMC transcript regions which encode for adrenocorticotropin (ACTH) 4-11 and beta endorphin 1-8, POMC mRNA was detected in very few motoneurones in unoperated or sham operated mice. After unilateral sciatic nerve section increases in the proportion of cells which expressed the POMC mRNA were seen in both the ipsilateral and contralateral ventral horns. The increase, like that seen for peptide immunoreactivity, was maximum at around 24 h and thereafter declined but at 7 days after the section the proportion of POMC mRNA-positive cells had returned to normal. Thus injury to the motoneurones is accompanied by synthesis of POMC-derived peptides via upregulation of the POMC gene in the motoneurone. PMID- 7984051 TI - Messenger RNA and protein expression of basic fibroblast growth factor receptor after cortical ablation. AB - In a previous report we demonstrated that basic fibroblast growth factor (bFGF), as a multipotent neurotrophic factor, could prevent retrograde degeneration of the thalamic neurons after ablation of the somatosensory cortex. To elucidate the mechanism of this bFGF action, we examined changes in FGF receptor (FGFR) mRNA (flg) expression with in situ hybridization. The FGF receptor protein was detected with the immunoblotting method. The FGFR mRNA expression was found to be diffusely increased in the affected cortex. Microscopic observation indicated that FGFR mRNA was expressed in several types of cortical cells including neurons and non-neuronal cells. This increase could be observed as early as 6 hours after surgery and lasted for 48 hours. In the thalamus, however no change in FGFR mRNA signals was observed. Western blotting detected a protein immunoreactive to anti FGFR antibody. Samples from the periablated cortex showed an increase in FGFR protein. Samples from the thalamus, however, showed no difference in FGFR protein level between the lesion side and the contralateral side. Application of exogenous bFGF in Gelfoam to the cortical ablation cavity did not show any effect on the gene expression or protein level of FGFR. These results suggest that FGFR is diffusely induced throughout the injured cortex in the early phase after injury and that bFGF may play an important role after injury. Topically applied bFGF might thus modulate cellular responses in the cortex and have a neurotrophic effect on the affected thalamic neurons. PMID- 7984053 TI - Re-examination of the ontogeny in the gene expression of DARPP-32 in the rat brain. AB - By in situ hybridization histochemistry, we have re-examined the ontogeny of the gene expression of mRNA encoding the dopamine- and cyclic AMP-regulated phosphoprotein with a molecular weight of 32,000, termed DARPP-32. On E13 and E15, weak expression signals were detected in the mantle zones and ventricular germinal zones of the fore-, mid-, hind-brain, and spinal cord. In the caudate putamen, the expression signals were first visible at its lateral margin on E15. The ventrolateral region of the caudate putamen expressed the gene intensely, while its ventricular germinal zone expressed it weakly on E18-20. Thereafter, the mRNA for DARPP-32 were expressed over the entire caudate putamen in patchy patterns. After birth, the expression levels in the caudate putamen increased markedly, with the majority of the neurons in the caudate putamen expressing the gene intensely on P7 and thereafter. In addition to the caudate putamen, expression signals were detected, albeit faintly, in the olfactory bulb, cortical plate, hippocampal pyramidal cell layer, and their ventricular zones on E18-20. The olfactory tubercle and medial habenular nucleus expressed the gene at slightly higher levels. In the cerebellum, the Purkinje cells showed progressively increasing gene expression from E20 to P7, whereas the external granule cell layer expressed the gene weakly. The ontogeny of the gene expression is largely consistent with previous immunohistochemical findings by other authors. Furthermore, the present finding suggests that DARPP-32 is involved in the regulation of the mitosis-related dephosphorylation by protein phosphatase 1 in the neuroepithelium. PMID- 7984052 TI - Neural control of dopamine beta-hydroxylase in vivo: acute and chronic effects. AB - Reserpine treatment was used to examine whether short- and long-term neural stimulation regulates rat adrenal medullary dopamine beta-hydroxylase (DBH, EC 1.14.17.1) through transcriptional activation and to examine the extent of coordinate control of DBH and phenylethanolamine N-methyltransferase (PNMT, EC 2.1.1.28). A single dose of reserpine (10 mg/kg i.p.) elevates DBH mRNA 1.5-fold by 6 h post-injection. Chronic treatment (10 mg/kg i.p., 4 alternate day injections) continues the rise in DBH mRNA, with a peak of 3.4-fold control values after 2 doses of reserpine and a plateau at this level thereafter. Even though DBH mRNA is elevated 6 h after a single injection of reserpine, DBH activity does not change in parallel. A 1.3-fold rise in activity occurs at 24 h post-injection. In contrast, chronic reserpine treatment concomitantly increases DBH activity and mRNA. As observed for DBH mRNA, enzyme activity peaks and plateaus after 2 injections on alternate days. However, the rise in enzymatic activity is less than the rise in mRNA (2.4-fold versus 3.4-fold). Ribosomal loading experiments demonstrate that the DBH mRNA pool is fully utilized for protein synthesis with an apparent decrease in the number of ribosomes loaded per molecule of mRNA. Western analysis and thermal denaturation studies indicate that an altered form of DBH may be expressed. With a single dose of reserpine, the enzyme shows a decline in specific activity while repeated treatment leads to an enzyme with higher specific activity. In both cases, the protein appears to be more stable. Reserpine treatment also markedly elevates adrenal glucocorticoids. A 1.5-fold increment in glucocorticoid receptor mRNA accompanies the corticosteroid rise, with the receptor mRNA peaking at 6 h and remaining at this level thereafter. The up-regulation of glucocorticoid receptor mRNA expression, together with the presence of a putative glucocorticoid response element in the 5' flanking region of the DBH gene, suggests that neural and hormonal regulatory mechanisms may work in concert to control DBH gene transcription. Finally, by comparison to PNMT, activation of DBH appears to require sustained stimulation of the neural axis, since acute changes in mRNA lead to only minor changes in enzyme expression. Similar to PNMT, continuous neural stimulation increases both DBH mRNA and enzymatic activity. However, the discordance in the magnitude of these indices suggests that other regulatory controls may be important in setting the ultimate limits on DBH expression, glucocorticoids perhaps being one such influence. PMID- 7984054 TI - Localization of phosphatase inhibitor-1 mRNA in the developing and adult rat brain in comparison with that of protein phosphatase-1 mRNAs. AB - The localization and ontogenic changes in the gene expression for phosphatase inhibitor-1 (I-1) were analyzed by in situ hybridization histochemistry, and they were compared with those for three catalytic subunits of protein phosphatase type 1 (PP-1). At the adult stage, intense expression signals for I-1 were detected in the hippocampal formation, piriform cortex, claustrum, dorsal endopiriform cortex, suprachiasmatic nucleus, choroid plexus, arachnoid membrane, and pineal body. Moderate expression signals for I-1 were observed in the olfactory neuronal layers, caudate putamen, layers II-IV, and VI of the neocortex, and cerebellar granule cells, whereas the expression levels were low in the thalamus, cerebellar Purkinje cells, and brain stem nuclei. Although the expression levels for the three PP-1 mRNAs varied notably in various brain regions, a relatively high and parallel expression of I-1 and PP-1 mRNAs was found in most regions of the forebrain. However, the dissociation in the expression levels between I-1 and PP 1 mRNAs was found in several loci: the laminar expression of I-1 mRNA versus the homogeneous expression of PP-1 mRNAs in the cerebral cortex; low levels of expression of I-1 mRNA versus relatively high expression of PP-1 mRNAs in the brain stem nuclei; high expression of I-1 mRNA in the arachnoid membrane versus low expression of PP-1 mRNAs in it. The unparallel expression was also seen in embryonic brain: No significant expression of I-1 mRNA versus substantial expression of PP-1 mRNAs in the ventricular zone and cerebellar external granular layer; transiently high expression of I-1 mRNA in developing thalamus versus constantly moderate to low expression of PP-1 mRNAs there. These findings suggest that I-1 may play some discrete roles independent of the regulation of PP-1 in certain regions and developing stages of the brain. PMID- 7984055 TI - Nerve growth factor induces expression of immediate-early genes NGFI-A (Egr-1) and NGFI-B (nur 77) in adult rat dorsal root ganglion neurons. AB - We have used primary cultures of adult rat dorsal root ganglia (DRG), enriched in sensory neurons, to investigate the induction of immediate-early genes by NGF and a variety of other growth factors. Using the polymerase chain reaction we have quantitatively amplified specific mRNA transcripts induced by NGF, in the presence and absence of the protein synthesis inhibitor cycloheximide. NGFIA (Egr 1) and NGFIB (nur 77) mRNAs were elevated in level within 60 min of NGF treatment and independently of de novo protein synthesis. This was consistent with the behaviour of immediate-early genes. These kinetics were seen at a range of NGF concentrations. NGFIA and NGFIB mRNAs were also found to be induced in DRG cultures by a variety of other growth factors. Different patterns of induction of NGFIA and NGFIB mRNA observed in DRG cultures suggested that transcript-specific pathways of signal transduction were operating within neurons, dependent upon the particular growth factor stimulus. Comparison of data reported from growth factor treatment of other cell types with data from DRG cultures also revealed patterns of NGFIA and NGFIB mRNA induction specific to DRG neurons. PMID- 7984056 TI - Distinctive rat brain immediate early gene responses to seizures induced by lithium plus pilocarpine. AB - The mRNA levels of four immediate early genes (IEG) were measured in rat brain regions 60 min after administration of pilocarpine (30 mg/kg) to lithium-treated (3 mmol/kg) rats, during generalized convulsive status epilepticus. Northern blots demonstrated induction of the genes in the order of c-fos = jun-B > c-jun > jun-D with large increases in the cerebral cortex, hippocampus, and striatum, a smaller increase in the cerebellum, and less in the brainstem. The mRNA levels of these four IEG were measured in rat cerebral cortex and hippocampus at several times after administration of the cholinergic agonist pilocarpine (5 or 30 mg/kg) with or without lithium pretreatment (3 mmol/kg, 16 h prior, or chronic 4 week dietary administration). Treatment with pilocarpine (30 mg/kg) alone increased mRNA levels in the order of c-fos > jun-B > c-jun but did not change the jun-D mRNA level, and maximal c-fos and jun-B mRNA levels occurred earlier (30 min) in the cortex than in the hippocampus. Treatment with the lower dose of pilocarpine (5 mg/kg) alone caused only small increases in c-fos and jun-B mRNA levels and these responses were unaffected by lithium pretreatment. Lithium pretreatment potentiated IEG expression induced by 30 mg/kg pilocarpine, likely as a result of the seizures caused by this combination of drugs because pretreatment with anticonvulsants (diazepam or MK-801) blocked seizures and the enhanced IEG mRNA levels. The mRNA levels were increased during seizures in the order of c-fos > jun-B > c-jun > jun-D in the hippocampus and jun-B > c-fos > c-jun > jun-D in the cortex, and were increased for a longer duration as well as to a greater extent than after administration of pilocarpine alone. Administration of pilocarpine (30 mg/kg) to rats treated chronically with lithium caused increases similar to those measured with acute lithium pretreatment. Thus the induction of IEG by cholinergic stimulation varied with dose, time, and brain region, and unique responses were observed for each of the IEG. Lithium pretreatment did not impair IEG expression induced by the lower dose of pilocarpine and greatly enhanced expression of IEG after administration of the higher dose of pilocarpine concomitant with seizure activity. PMID- 7984057 TI - The molecular cloning and expression of a human synaptic vesicle amine transporter that suppresses MPP+ toxicity. AB - A synaptic vesicle amine transporter cDNA, termed hSVAT, has been isolated by the reverse transcription and polymerase chain reaction (PCR) technique from human substantia nigra and subsequent screening of a human substantia nigra library. The hSVAT sequence obtained is highly homologous to the rat SVAT sequence (92% homology) and is essentially identical to the human sequence identified recently by Surratt and colleagues [33]. This labelled hSVAT cDNA detected a single band (approximately 5.0 kb) when used as a probe for Northern analysis of human nigral RNA extract. In situ hybridization studies using hSVAT specific antisense oligonucleotides showed a strong hybridization signal concentrated over the cells of the substantia nigra pars compacta. This cDNA sequence when expressed in chinese hamster ovary (CHO) cells conferred resistance to MPP+ the toxic metabolite of MPTP and cells containing it accumulated dopamine. PMID- 7984058 TI - Expression of the anion exchanger (AE) gene family in human brain. Identification of a new AE protein: AE0. AB - We present the first identification of proteins of the anion exchanger (AE) gene family expressed in human brain. Expression was established by the reverse transcriptase-polymerase chain reaction (RT-PCR), performed on RNA isolated from frontal cortex tissue. The erythroid form AE1, the major non-erythroid form AE2, and a novel member of the AE family, which we named AE0, were identified. Immunohistochemical analysis revealed the highest expression of these proteins in large pyramidal neurons in the frontal cortex and hippocampus. The sequence of the membrane domain of AE0 is identical to that of the major erythroid species AE1, except for the third extracellular loop, which contains a 25 amino acid insertion. This insertion is identical to a sequence in the third extracellular loop of AE2. Expression of AE0 is not restricted to brain tissue, since we could also detect AE0-mRNA in T-lymphocytes and reticulocytes. Chromosomal mapping indicates that the AE0 gene is most likely located on human chromosome 22. We did not find any indications for qualitative changes in AE1, AE2, or AE0 in Alzheimer brain tissue. PMID- 7984059 TI - Band-selective spin echoes for in vivo localized 1H NMR spectroscopy. AB - This study describes a new single spin-echo spatial localization sequence, BASSALE or BAnd-Selective Spin echo Acquisition for Localized Editing, that overcomes a number of the limitations of the STEAM and PRESS volume selection pulse sequences. It achieves conformal volume localization in a single shot by spatially tailored suppression of all magnetization outside a 2D region of interest followed by selection of a single orthogonal slice. This separation of spatial localization from the echo formation process has permitted use of a spectrally selective cosine-modulated sinc refocusing pulse to acquire localized 1H spectra with the water suppression efficiency of STEAM and the sensitivity of PRESS. Echoes formed by such spectrally selective pulses have been termed band selective spin echoes. The BASSALE sequence attains shorter echo times than PRESS, inhibits scalar spin-spin interactions to permit localized editing and T2 relaxometry of metabolites with J-coupled spins (e.g., lactate), is insensitive to homonuclear multiple-quantum and polarization transfer effects, and can be made sensitive or insensitive to spin displacement effects. Applications are shown both with phantoms and in situ in the rat brain. PMID- 7984060 TI - Correlation of spectroscopy and magnetization transfer imaging in the evaluation of demyelinating lesions and normal appearing white matter in multiple sclerosis. AB - Magnetization transfer imaging (MT) and localized proton spectroscopy (1H-MRS) were utilized in the evaluation of lesions (high signal abnormalities on T2 weighted images) and normal-appearing white matter (NAWM) in multiple sclerosis (MS). Eleven patients with a clinical diagnosis of MS were independently evaluated with both 1H-MRS and MT. The magnetization transfer ratio (MTR) of lesions was compared with the relative concentration of N-acetyl-aspartate (NAA) and a composite peak at 2.1 to 2.6 ppm termed "marker peaks." The MTR of white matter lesions in the MS patients was markedly decreased (6-34%; normal approximately 42%), and correlated well with increase in the marker peaks region (0.94-3.89). There was no correlation between the relative concentration of NAA and MTR. Increased resonance peaks in the 2.1 to 2.6 ppm range and marked decreases in MTR may be a relatively specific indicators of demyelination. PMID- 7984062 TI - Glucose metabolism in RIF-1 tumors after reduction in blood flow: an in vivo 13C and 31P NMR study. AB - Low pH appears to enhance the effectiveness of therapeutic hyperthermia. 13C and 31P NMR spectroscopy have been employed to examine the possibility that elevating glucose in a solid tumor while simultaneously reducing tumor blood flow would induce a more profound acidosis than either treatment alone. When blood flow in RIF-1 tumors was acutely reduced by administration of hydralazine and additional glucose was delivered locally by intratumoral injection, tumor acidosis (as determined by 31P NMR spectroscopy) during the period of reduced blood flow was not enhanced, relative to administration of hydralazine alone. Tumor NTP/P1 ratios decreased significantly within 20 min of hydralazine administration, whether or not glucose was injected, although NTP/P1 ratios were slightly higher in tumors that received extra glucose. Tumor lactate concentrations were not significantly different in glucose-supplemented tumors, despite glucose concentrations that were 4 to 5 times higher. When the added glucose was labeled with 13C, no correlation was detected between the pH in an individual tumor and the intensity of the 3-[13C]-lactate resonance in the same tumor. PMID- 7984061 TI - Analysis of macromolecule resonances in 1H NMR spectra of human brain. AB - Macromolecule resonances underlying metabolites in 1H NMR spectra were investigated in temporal lobe biopsy tissue from epilepsy patients and from localized 1H spectra of the brains of healthy volunteers. The 1H NMR spectrum of brain tissue was compared with that of cytosol and dialyzed cytosol after removal of low molecular weight molecules (< 3500 daltons) at 8.4 and 2.1 Tesla. The assignment of specific resonances to macromolecules in 2.1 Tesla, short-TE, localized human brain 1H NMR spectra in vivo was made on the basis of a J-editing method using the spectral parameters (delta, J) and connectivities determined from 2D experiments in vitro. Two prominent connectivities associated with macromolecules in vitro (0.93-2.05 delta and 1.6-3.00 delta) were also detected in vivo by the J-editing method. Advantage was taken of the large difference in measured T1 relaxation times between macromolecule and metabolite resonances in the brain spectrum to acquire 'metabolite-nulled' macromolecule spectra. These spectra appear identical to the spectra of macromolecules isolated in vitro. PMID- 7984063 TI - In vitro and in vivo 13C and 31P NMR analyses of phosphocholine metabolism in rat glioma cells. AB - In vivo magnetic resonance spectroscopy (MRS) has revealed that phosphomonoesters (PME) such as phosphocholine (PCho) and phosphoethanolamine (PEth) are elevated in tumors and rapidly proliferating tissues. The regulation of PME levels and their relationship to proliferation are not well known. In the present study, we investigated the regulation of PCho and PEth levels in rat glioma cells grown in vivo and in vitro using 31P and 13C MRS. However, the ability of cells to produce choline endogenously is variable. To fully understand regulation of PCho levels, it is necessary to characterize the activity of the endogenous pathway, if it exists. This was first investigated by following the metabolic fate of 13C labeled methionine of 9L glioma tumors in vivo. Our results indicate that there is a significant amount of de novo choline synthesis in vivo. However, similar experiments performed in vitro using cells cultured in bioreactors indicated that glioma cells themselves are unable to synthesize choline de novo, suggesting that the in vivo results were due to the involvement of extra-tumoral organs, e.g., liver. Further in vitro experiments demonstrated that the uptake and phosphorylation of physiologically relevant concentrations of exogenous choline is very active in these systems. Thus, it appears that the exogenous pathway for PCho biosynthesis predominates and regulates PCho levels in glioma cells. Our results also demonstrate that PCho levels are lowest, and PEth levels are highest, in non-proliferating cells. These observations indicate that there is a decrease in the biosynthesis of PCho concomitant with a reduction in culture growth. The source of the increased PEth is, as yet, undefined. PMID- 7984064 TI - Inversion recovery EPI of bolus transit in rat myocardium using intravascular and extravascular gadolinium-based MR contrast media: dose effects on peak signal enhancement. AB - Inversion recovery gradient recalled echo planar imaging (TI/TR/TE = 700/2000/10 ms) was used to dynamically monitor the first pass of an intravascular (GdDOTA polylysine) and an extravascular (GdDTPA-BMA) contrast agent through normal rat myocardium. It was found that myocardial enhancement increased with dose of the intravascular agent to a limiting value of approximately 50% of fully relaxed intensity, consistent with enhancement of 40% of myocardial water content during the first pass. Larger doses produced no further increase in peak response. On the other hand, the extravascular agent caused incrementally increased enhancement throughout the dose range examined to a final value of 68 +/- 2% of fully relaxed intensity. The profile of dose dependence for both agents was inconsistent with monoexponential T1 relaxation. It was concluded that: (a) compartmentalization of myocardial water combined with restricted myocardial water diffusion limits the peak response during bolus transit; (b) extraction of the extravascular agent during transit elevates the peak response over that obtained from agent confined to the vascular volume; and (c) models that assume simple monoexponential T1 relaxation to derive time-density curves do not adequately describe the relationship between changes in signal intensity, R1 and contrast concentration. PMID- 7984065 TI - Reconstructions of phase contrast, phased array multicoil data. AB - We present a reconstruction method for phased array multicoil data that is compatible with phase contrast MR angiography. The proposed algorithm can produce either complex difference or phase difference angiograms. Directional flow and quantitative information are preserved with the phase difference reconstruction. The proposed method is computationally efficient and avoids intercoil cancellation errors near the velocity aliasing boundary. Feasibility of the method is demonstrated on human scans. PMID- 7984066 TI - Assessment of relative brain iron concentrations using T2-weighted and T2* weighted MRI at 3 Tesla. AB - In this paper a new method is presented for the relative assessment of brain iron concentrations based on the evaluation of T2 and T2*-weighted images. A multiecho sequence is employed for rapid measurement of T2 and T2*, enabling calculation of the line broadening effect (T2'). Several groups have failed to show a correlation between T2 and brain iron content. However, quantification of T2', and the associated relaxation rate R2', may provide a more specific relative measure of brain iron concentration. This may find application in the study of brain diseases, which cause associated changes in brain iron levels. A new method of field inhomogeneity correction is presented that allows the separation of global and local field inhomogeneities, leading to more accurate T2* measurements and hence, T2' values. The combination of T2*, and T2-weighted MRI methods enables the differentiation of Parkinson's disease patients from normal age matched controls based on differences in iron content within the substantia nigra. PMID- 7984068 TI - Modeling and observation of temperature changes in vivo using MRI. AB - Models have been developed for the signal changes occurring in human peripheral muscle after thermal stress for some methods of measuring temperature in vivo. These include the dependency of T1 on temperature, observed by both direct, and magnetization transfer, experiments, and the temperature sensitivity of the diffusion coefficient and the chemical shift of the water proton line. Results show the relative complexity of the T1-dependent models when there are significant variations in, possibly amongst other things, tissue perfusion, and how the predictions made using them match the behavior of the practical values quite well. Using changes in the diffusion coefficient appears less problematic, although there can still be significant errors in temperature calibrations. The problems with this approach are likely to be due to the consequences of anisotropy in tissue. PMID- 7984067 TI - Dual-echo MRI segmentation using vector decomposition and probability techniques: a two-tissue model. AB - We combined a vector decomposition technique with Gaussian probability thresholding in feature space to segment normal brain tissues, tumors, or other abnormalities on dual-echo MR images. The vector decomposition technique assigns to each voxel a fractional volume for each of two tissues. A probability threshold, based on an assumed Gaussian probability density function describing random noise, isolates a region in feature space for fractional volume calculation that minimizes contamination from other tissues. The calculated fractional volumes are unbiased estimates of the true fractional volumes. The contrast-to-noise ratio (CNR) between tissues on the segmented images is the same as the Euclidean norm of CNRs in the original images. The method is capable of segmenting more than two tissues from a set of dual-echo images by sequentially analyzing different pairs of tissues. The model is analyzed mathematically and in experiments with a phantom. Two clinical examples are presented. PMID- 7984069 TI - Noninvasive measurement of renal hemodynamic functions using gadolinium enhanced magnetic resonance imaging. AB - A technique for the assessment of single kidney hemodynamic functions utilizing a novel MR pulse sequence in conjunction with MR contrast material administration is described. Renal extraction fraction (EF) is derived by measuring the concentration of the incoming contrast agent in the renal artery and the outgoing concentration in the renal vein. The glomerular filtration rate (GFR) can then be determined by the product of EF and renal plasma flow. A modified inversion recovery MR pulse sequence is used to measure the T1 of moving blood. This pulse sequence uses a spatially nonselective inversion pulse. A series of small flip angle detection pulses are then used to monitor the recovery of longitudinal spin magnetization in an image plane intersecting the renal vessels. The recovery rate is measured in each vessel and the T1 of blood determined. These T1 measurements are then used to determine the ratio of contrast concentration in the renal arteries and veins. Blood flow measurements can be obtained simultaneously with T1 measurements by inserting flow-encoding magnetic field gradients into the pulse sequence. Preliminary results in human volunteers suggest the feasibility of noninvasively determining hemodynamic functions with magnetic resonance. PMID- 7984070 TI - Analysis and correction of motion artifacts in diffusion weighted imaging. AB - For diffusion-weighted magnetic resonance imaging and under circumstances where patient movement can be modeled as rigid body motion, it is shown both theoretically and experimentally that translations and rotations produce phase errors which are zero- and first-order, respectively, in position. While a navigator echo can be used to correct the imaging data for arbitrary translations, only when the diffusion gradient is applied in the phase encode direction is there sufficient information to correct for rotations around all axes, and therefore for general rigid body motion. Experiments in test objects and human brain imaging confirm theoretical predictions and demonstrate that appropriate corrections dramatically improve image quality in vivo. PMID- 7984071 TI - Relaxivity corrected response modulated excitation (RME): a T2-corrected technique achieving specified magnetization patterns from an RF pulse and a time varying magnetic field. AB - We have reworked the theory of RF excitation to enable correction for relaxivity while designing response-modulated excitation (RME) to achieve specified magnetization targets. This results in a significant improvement in the ability to achieve a specified target magnetization, especially if excitation time is long or T2 is short. The methods presented may also be used to improve the quality of spatial-spectral pulses as well as localized spectroscopy, real-time imaging, real-time localized velocity, and noninvasive pressure measurement. PMID- 7984072 TI - Thin film high temperature superconducting RF coils for low field MRI. AB - We have built and tested a thin-film high temperature superconducting (HTS) surface coil for MRI at 0.064T. When placed as close as possible to a conductive sample, the 6.7-cm outer diameter HTS coil had a measured signal-to-noise ratio (SNR) 1.8 times higher than a room temperature copper coil of similar size and location. Our results predict that in some cases, SNR gains of about a factor of 2 can be attained in low-field MRI systems by substituting HTS surface coils for copper coils. PMID- 7984073 TI - In vivo 31P NMR studies of orientation effects upon rat brain metabolism during mild hypoxia. AB - Energy metabolites in rat brain under the same level of hypoxia were monitored by 31P NMR in both horizontal and vertical magnets. The changes in PCr, Pi, and pHi in the vertical setting toward the end of hypoxia were significantly larger and the recovery in the horizontally held animals was more complete. The results demonstrated quantitatively that the stress of the alignment is superimposed on the stress of hypoxia in the vertical magnet. PMID- 7984074 TI - Metabolic loss of deuterium from isotopically labeled glucose. AB - The isotopically substituted molecule (6-13C, 1, 6, 6-2H3)glucose was evaluated to determine whether metabolic 2H loss would prevent its use in quantitating pentose phosphate pathway (PPP) activity. PPP activity causes the C1 of glucose to be lost as CO2, while C6 can appear in lactate. 2H NMR analysis of the lactate produced from this glucose can distinguish (3-2H)-lactate (from C1 of glucose) from (3-13C, 3, 3-2H2)lactate (from C6 of glucose). 2H NMR spectroscopic analysis of medium containing (6-13C, 1, 6, 6-2H3)glucose after incubation with cultured rat 9L glioma cells suggested a 30.8 +/- 2.1% PPP activity as compared with 6.0 +/- 0.8% from separate, parallel incubations with (1-13C)glucose and (6 13C)glucose. Subsequent experiments with other isotopically labeled glucose molecules suggest that this discrepancy is due to selective loss of 2H from the C1 position of glucose, catalyzed by phosphomannose isomerase. Failure to consider 2H exchange from the C1 and C6 positions of glucose can lead to incorrect conclusions in metabolic studies utilizing this and other deuterated or tritiated glucose molecules. PMID- 7984075 TI - Turbine flow sensor for volume-flow rate verification in MR. AB - A turbine flow sensor for MR flow experiments has been evaluated using reference volume-flow rate measurements obtained using an electromagnetic (EM) flow meter measurements and simultaneous phase contrast (PC) MR acquisitions. After calibration, the device was found to have accuracy (compared with the EM flow meter), linearity, and precision of better than +/- 1%, +/- 3.5%, 3.5%, respectively, in constant flow mode (0 to 30 ml s-1). The frequency response of the flow sensor was flat (within +/- 10%) up to 13.9 Hz. Volume-flow rate measurements on constant and simulated physiologic flow waveforms were in close agreement with both the electromagnetic (EM) flow meter and the gated MR PC estimates. PMID- 7984076 TI - On the field inhomogeneity of a birdcage coil. AB - A mathematical model is developed for the numerical analysis of birdcage coils constructed using capacitors having different capacitance. With the aid of this model, it is shown that the deviation of some capacitance introduced by tune, balance, and drive mechanisms can cause inhomogeneity in the B1 field produced by the coil. Useful curves and formulae are developed to provide a guideline for the design of birdcage coils. PMID- 7984078 TI - Fast volume scanning with frequency-shifted BURST MRI. AB - We introduce a modified BURST imaging technique with reduced saturation effects and improved signal-to-noise ratio. The method applies a frequency shift to the RF excitation pulse on successive repetitions. It allows collection of 3D datasets of human brain within a few seconds, on a standard clinical scanner at 1.5 Tesla. PMID- 7984077 TI - In vivo measurement of water diffusion in the human heart. AB - Existing magnetic resonance methods for diffusion imaging, including echo planar, are ineffective in the beating heart due to motion-induced signal attenuation. To overcome this problem, we used a diffusion-weighted stimulated echo-echo planar magnetic resonance imaging sequence. The two lobes of the diffusion-sensitizing gradient were synchronized to the same point in successive cardiac cycles in order to fix the cardiac position and avoid bulk motion effects. The apparent diffusion coefficients (ADCs) of the interventricular septum in 12 healthy subjects for diffusion gradients along the x-, y-, and z-directions were 1.40 +/- 0.27, 1.48 +/- 0.35, and 1.78 +/- 0.27 x 10(-3) mm2/s. The ADCs of the interventricular septum in a second group of 15 healthy subjects for diffusion gradients along the short axis, horizontal and vertical long axes were 0.92 +/- 0.15, 1.50 +/- 0.15, and 1.10 +/- 0.24 x 10(-3) mm2/s. Because the ADCs were less than the measured values for skeletal muscle and their standard deviations were low, it seems unlikely that bulk motion effects made the dominant contribution to the measured myocardial ADC for the interventricular septum, although motion and/or susceptibility artifacts frequently degraded measurements in the free wall of the left ventricle. Additional evidence that ADC was not predominantly determined by wall motion was obtained in a third group of patients with various cardiac abnormalities, in whom there was only a weak correlation between ADC and ejection fraction.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7984079 TI - Suicide as an outcome for medical disorders. AB - The association between suicide and medical disorder has not received as much attention as the association between suicide and psychiatric disorder. We identified by statistical overview medical disorders with an altered suicide risk. We found reports on the mortality of 63 medical disorders (ICD9 001-289, 320-999) said to have an altered suicide risk. English-language reports were located on MEDLINE with the search terms "disease name with mortality and follow up"; and from the reference lists of these reports. We abstracted 235 reports of mortality studies of medical disorders with 2 years or more of follow-up, less than 10% loss of subjects, observed numbers of suicides given, and either the expected number or the facts from which to derive this. The ratio of the sum of the observed to the sum of the expected suicides, for each disorder, tested by the Poisson distribution gave an assessment of altered risk of death from suicide. Increased risk (p < 0.05) was seen for HIV/AIDS, malignant neoplasms as a group, head and neck cancers, Huntington disease, multiple sclerosis, peptic ulcer, renal disease, spinal cord injury, and systemic lupus erythematosus. Inconclusive evidence for increased risk was observed for amputation, heart valve replacement and surgery, disorders of the intestine (Crohn disease, ileostomy, ulcerative colitis), hormone replacement therapy, alcoholic liver disease, neurofibromatosis, systemic sclerosis, and Parkinson disease. Pregnancy and the puerperium had decreased risks (p < 0.05). There was no evidence of either increased or decreased risk for any of the other disorders studied. PMID- 7984080 TI - Suicide and medical afflictions. PMID- 7984081 TI - Pacemaker endocarditis. Report of 44 cases and review of the literature. AB - We conducted a retrospective study to characterize the clinical course, microbiologic spectrum, and risk factors for endocarditis and for associated mortality in a large series of patients with documented pacemaker endocarditis. Using a computerized search through the medical records of 10 major hospitals in Israel from 1982 to 1992, and carefully reviewing the charts, we identified 44 patients with pacemaker endocarditis. The cases were categorized as definite (n = 25), probable (n = 12), or possible (n = 7) infective endocarditis based on strict case definition. Fever and chills were the most common symptoms. Increased ESR, leukocytosis, microscopic hematuria, and anemia were the most common laboratory findings. A relatively high proportion of the patients were diabetic. The most common source of endocarditis was infection acquired by the placement procedure or infection of the pacemaker pouch. Demographic, clinical, and laboratory features were similar to those of endocarditis patients of a similar age range without pacemakers, although the frequency of fever and chills was higher in our patients than in those patients and splenomegaly, vascular embolic phenomena, and new or changing murmurs were rare in our patients. The major pathogens were Staphylococcus aureus and Staphylococcus epidermidis, similar to other series of pacemaker-associated bacteremia and similar to the microbiologic findings of early prosthetic-valve endocarditis. However, this microbiologic profile is different from that of native-valve endocarditis. Although the present series did not show a statistically significant advantage to electrode removal over conservative treatment, when analyzed together with pooled data from other studies, it suggests that the surgical approach is preferable.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7984084 TI - "Wegener's granulomatosis": the path traveled since 1931. PMID- 7984082 TI - Extracerebral toxoplasmosis in patients infected with HIV. A French National Survey. AB - A French nationwide survey of extracerebral toxoplasmosis (ECT) in HIV-infected patients was performed between January 1990 and September 1992. All French hospitals were surveyed, and all but a few responded. Data collected included epidemiologic, clinical, and biologic features; therapy; and outcome. During the 33-month survey, 199 cases were collected. The prevalence of ECT in patients with AIDS can be estimated at 1.5%-2%. Age, sex, and HIV risk factors were similar to those of the general AIDS population in France. Extracerebral toxoplasmosis appeared mainly in HIV-infected patients with advanced immunosuppression: the mean CD4+ lymphocyte count was 57/mm3(+/- 99). The localizations observed were: eyes (50% of patients); lung (26%); disseminated (at least 2 extracerebral visceral localizations) (11.5%); peripheral blood (acute febrile syndrome with isolated positive parasitemia) (3%); heart (3%); bone marrow (3%); bladder (1%); and isolated cases of rhinopharynx, skin, liver, lymph nodes, conus medullaris, and pericardium. In this survey, muscular and pancreatic localizations were always associated with other extracerebral localizations. A cerebral localization was diagnosed in 41% of cases. Serologic data provided little information. Ocular fundus examination, bronchoalveolar lavage, tissue biopsy, and search for parasitemia were the main diagnostic procedures. Treatment was the same as for cerebral toxoplasmosis. A clinical response was observed in 64% of cases; 19% relapsed. Death occurred in 106 (53%) cases and was related to ECT in 34% of cases.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7984083 TI - Wegener's granulomatosis: studies in eighteen patients and a review of the literature. 1973. PMID- 7984085 TI - Cloning and sequencing of Vibrio cholerae mannose-sensitive haemagglutinin pilin gene: localization of mshA within a cluster of type 4 pilin genes. AB - The mannose-sensitive haemagglutinin (MSHA) pilus that is associated with Vibrio cholerae strains of El Tor biotype has been shown to be a potential colonization factor and protective antigen. The gene encoding the structural subunit of MSHA pili was cloned from size-fractionated SacI-cleaved chromosomal DNA in the expression phage vector lambda ZAPII. Positive clones carried a c. 5.3 kb SacI fragment and were identified on the basis of MSHA expression and hybridization with a synthetic oligonucleotide probe based upon the N-terminus of MshA, the structural subunit of MSHA. The mshA gene was localized to a 2.6 kb SalI-EcoRI fragment, which was subcloned and shown to express MshA from its own promoter in Escherichia coli. Nucleotide sequencing of the entire fragment revealed six open reading frames (ORFs) of which four were complete. The mshA gene encodes an 18,094 Da prepilin protein, which in its mature form has a size of 17,436 Da. MshA is a type 4 (N-MePhe) pilin protein that is more homologous to pilins produced by Pseudomonas aeruginosa and Neisseria gonorrhoeae than to TcpA, the structural subunit of the toxin-coregulated pilus of V. cholerae. The protein seems to be directly involved in receptor binding, as an in-frame mutation in the mshA gene was found to abolish both D-mannose-dependent haemagglutination and binding of V. cholerae bacteria to D-mannose-containing agarose beads. Three additional ORFs, all in the same transcriptional orientation as mshA, were found to encode type 4 pilin-like proteins. A potential promoter with a sequence homologous to that of cAMP-CRP-activated promoters in E. coli was identified upstream of ORF3, the gene preceding mshA. PMID- 7984086 TI - The HAP2,3,4 transcriptional activator is required for derepression of the yeast citrate synthase gene, CIT1. AB - The yeast nuclear gene CIT1 encodes mitochondrial citrate synthase, which catalyses the first and rate-limiting step of the tricarboxylic acid (TCA) cycle. Transcription of CIT1 is subject to glucose repression. Mutations in HAP2, HAP3 or HAP4 block derepression of a CIT1-lacZ gene fusion. The HAP2,3,4 transcriptional activator also activates nuclear genes encoding components of the mitochondrial electron transport chain, and thus it co-ordinates derepression of two major mitochondrial functions. Two DNA sequences resembling the consensus HAP2,3,4-binding site (ACCAATNA) are located at approximately -310 and -290, upstream of the CIT1 coding sequence. Deletion and mutation analysis indicates that the -290 element is critical for activation by HAP2,3,4. Glucose-repressed expression of CIT1 is largely independent of HAP2,3,4, is repressed by glutamate, and requires a DNA sequence between -367 and -348. Evidence is presented for a second HAP2,3,4-independent activation element located just upstream and overlapping the -290 HAP2,3,4 element. PMID- 7984087 TI - Role of hns in the virulence phenotype of pathogenic salmonellae. AB - A TnphoA-generated mutant C5060, attenuated for virulence, was derived from the mouse-virulent Salmonella typhimurium strain C5. This mutation, designated hns 112::TnphoA, harbours the transposon in the 3' end of hns, with the alkaline phosphatase open reading frame in the opposite orientation to that of hns. Bacterial strains harbouring hns-112::TnphoA were mucoid and had altered levels of DNA supercoiling, as monitored using pUC18 as a reporter plasmid. Transduction of hns-112::TnphoA into mouse virulent strains, including S. typhimurium SL1344 and Salmonella enteritidis Se795, resulted in attenuation. When an independent hns mutation, harbouring a kanamycin-resistance cassette inserted into the Kpnl site at base pair 237 of the hns gene, was introduced into S. typhimurium C5, the isolates were also attenuated. S. typhimurium C5 isolates harbouring the multicopy plasmid pGB651, which encodes the Escherichia coli hns gene, were partially attenuated in mice. Transductional analysis, using Tn10 insertions located close to the hns gene, showed that virulence could be restored in genetic crosses that eliminated the resident hns mutations. However, some hns+ transductants were still attenuated, suggesting that secondary attenuating lesions can accumulate in hns-deficient strains. These studies show that the hns locus plays a role in Salmonella virulence. PMID- 7984088 TI - The virulence regulator protein of Listeria ivanovii is highly homologous to PrfA from Listeria monocytogenes and both belong to the Crp-Fnr family of transcription regulators. AB - The two pathogenic Listeria species, L. ivanovii and L. monocytogenes, can be differentiated biochemically and show different host ranges. Virulence of L. monocytogenes is dependent on the integrity of prfA which positively and co ordinately regulates transcription of several virulence genes. Until now, a prfA homologue had not been identified in L. ivanovii. We have now cloned a chromosomal region from L. ivanovii comprising two genes with high homology to the plcA and prfA genes from L. monocytogenes. Distal from prfA, an open reading frame highly homologous to a phosphoribosyl pyrophosphate synthetase gene (prs) was newly identified, defining the border of the virulence gene cluster. Transcription of the gene for ivanolysin O and expression of other genes of the virulence gene cluster in L. ivanovii were dependent on PrfA. The pattern of PrfA dependent proteins (PdPs) expressed in L. ivanovii was similar, but not identical to that of L. monocytogenes. The PrfA proteins, as predicted from nucleotide sequences of both pathogenic Listeria species, are very similar and show significant homology to the Crp-Fnr family of global transcription regulators. PMID- 7984089 TI - The human gastric pathogen Helicobacter pylori has a gene encoding an enzyme first classified as a mucinase in Vibrio cholerae. AB - The human bacterial pathogen Helicobacter pylori has been suggested to be the causative agent of the most common chronic infection of man. Since its first isolation in 1982, H. pylori has been associated with gastric and duodenal ulcer disease, and more recently, gastric cancer. The proteolytic digestion of gastric mucus by this microorganism has been suggested as an important mechanism by which its pathogenicity is at least partly exerted. Here we report the detection of protease activity in H. pylori total-cell and supernatant extracts. On the basis that zinc metalloproteases are common microbial pathogenicity factors, we identified a single protein in H. pylori protein extracts with antibodies to the Pseudomonas aeruginosa elastase (a secreted zinc metalloprotease). This same protein was identified by pooled serum from patients infected with H. pylori. We used the functional and immunological relationship between the P. aeruginosa elastase and the Vibrio cholerae haemagglutinin/protease (HAP) to clone the H. pylori hap gene, which was over 99% similar to the V. cholerae hap gene in the coding region. A 4 kb DNA fragment containing the entire cloned gene was highly unstable in Escherichia coli and Bacillus subtilis cloning vectors. We also demonstrated that a hap-like gene sequence is present in all nine Helicobacter species so far discovered. The V. cholerae HAP was first classified on the basis of its mucinase activity. PMID- 7984090 TI - A small (2.4 Mb) Bacillus cereus chromosome corresponds to a conserved region of a larger (5.3 Mb) Bacillus cereus chromosome. AB - We have determined the sizes of the chromosomes of six Bacillus cereus strains (range 2.4-4.3 Mb) and constructed a physical map of the smallest B. cereus chromosome (2.4 Mb). This map was compared to those of the chromosomes of four B. cereus strains and one B. thuringiensis strain previously determined to be 5.4 6.3 Mb. Of more than 50 probes, 30 were localized to the same half of the larger B. cereus and B. thuringiensis chromosomes. All 30 were also present on the small chromosome. Twenty of the probes present on the other half of the larger chromosomes were either present on extrachromosomal DNA, or absent from the B. cereus strain carrying the small chromosome. We propose that the genome of B. cereus/B. thuringiensis has one constant part and another less stable part which is more easily mobilized into other genetic elements. This part of the genome is localized to one region of the chromosome and may be subject to deletions or more frequent relocations between the chromosome and episomal elements of varying sizes up to the order of megabases. PMID- 7984091 TI - When replication forks stop. AB - DNA synthesis is an accurate and very processive phenomenon, yet chromosome replication does not proceed at a constant rate and progression of the replication fork can be impeded. Several structural and functional features of the template can modulate the rate of progress of the replication fork. These include DNA secondary structures, DNA damage and occupied protein-binding sites. In addition, prokaryotes contain sites where replication is specifically arrested. DNA regions at which the replication machinery is blocked or transiently slowed could be particularly susceptible to genome rearrangements. Illegitimate recombination, a ubiquitous phenomenon which may have dramatic consequences, occurs by a variety of mechanisms. The observation that some rearrangements might be facilitated by a pause in replication could provide a clue in elucidating these processes. In support of this, some homologous and illegitimate recombination events have already been correlated with replication pauses or arrest sites. PMID- 7984092 TI - Nod factors of Rhizobium are a key to the legume door. AB - Symbiotic interactions between rhizobia and legumes are largely controlled by reciprocal signal exchange. Legume roots excrete flavonoids which induce rhizobial nodulation genes to synthesize and excrete lipo-oligosaccharide Nod factors. In turn, Nod factors provoke deformation of the root hairs and nodule primordium formation. Normally, rhizobia enter roots through infection threads in markedly curled root hairs. If Nod factors are responsible for symbiosis-specific root hair deformation, they could also be the signal for entry of rhizobia into legume roots. We tested this hypothesis by adding, at inoculation, NodNGR-factors to signal-production-deficient mutants of the broad-host-range Rhizobium sp. NGR234 and Bradyrhizobium japonicum strain USDA110. Between 10(-7) M and 10(-6) M NodNGR factors permitted these NodABC- mutants to penetrate, nodulate and fix nitrogen on Vigna unguiculata and Glycine max, respectively. NodNGR factors also allowed Rhizobium fredii strain USDA257 to enter and fix nitrogen on Calopogonium caeruleum, a nonhost. Detailed cytological investigations of V. unguiculata showed that the NodABC- mutant NGR delta nodABC, in the presence of NodNGR factors, entered roots in the same way as the wild-type bacterium. Since infection threads were also present in the resulting nodules, we conclude that Nod factors are the signals that permit rhizobia to penetrate legume roots via infection threads. PMID- 7984093 TI - Characterization of broadly pleiotropic phenotypes caused by an hfq insertion mutation in Escherichia coli K-12. AB - The region immediately downstream from the miaA tRNA modification gene at 94.8 min contains the hfq gene and the hflA region, which are important in the bacteriophage Q beta and lambda life cycles. The roles of these genes in bacteria remain largely unknown. We report here the characterization of two chromosomal hfq insertion mutations. An omega (omega) cassette insertion near the end of hfq resulted in phenotypes only slightly different from the parent, although transcript mapping demonstrated that the insertion was completely polar on hflX expression. In contrast, an equally polar omega cassette insertion near the beginning of hfq caused pronounced pleiotropic phenotypes, including decreased growth rates and yields, decreased negative supercoiling of plasmids in stationary phase, increased cell size, osmosensitivity, increased oxidation of carbon sources, increased sensitivity to ultraviolet light, and suppression of bgl activation by hns mutations. hfq::omega mutant phenotypes were distinct from those caused by omega insertions early in the miaA tRNA modification gene. On the other hand, both hfq insertions interfered with lambda phage plaque formation, probably by means of polarity at the hflA region. Together, these results show that hfq function plays a fundamental role in Escherichia coli physiology and that hfq and the hflA-region are in the amiB-mutL-miaA-hfq-hflX superoperon. PMID- 7984094 TI - Rhizobium meliloti DctD, a sigma 54-dependent transcriptional activator, may be negatively controlled by a subdomain in the C-terminal end of its two-component receiver module. AB - Rhizobium meliloti DctD is believed to have three functional domains: an N terminal, two-component receiver domain; and like other sigma 54-dependent activators, C-terminal and central domains for DNA binding and transcription activation. We have characterized a progressive series of N-terminal deletions of R. meliloti DctD. The N-terminal domain was not needed for binding the dctA upstream activation sequence. Only 25% of the C-terminal end of the receive domain was needed to significantly inhibit the central domain, and proteins lacking up to 60% of the N-terminal end of the receiver domain were 'inducible' in R. meliloti cells. We hypothesize that the N-terminal two-thirds of the DctD receiver domain augments and controls an adjacent subdomain for inhibiting the central domain. PMID- 7984097 TI - DNA repair in the extremely radioresistant bacterium Deinococcus radiodurans. AB - Deinococcus radiodurans and other members of the same genus share extraordinary resistance to the lethal and mutagenic effects of ionizing and u.v. radiation and to many other agents that damage DNA. While it is known that this resistance is due to exceedingly efficient DNA repair, the molecular mechanisms responsible remain poorly understood. Following very high exposures to u.v. irradiation (e.g. 500 J m-2, which is non-lethal to D. radiodurans), this organism carries out extremely efficient excision repair accomplished by two separate nucleotide excision repair pathways acting simultaneously. One pathway requires the uvrA gene and appears similar to the UvrABC excinuclease pathway defined in Escherichia coli. The other excision repair pathway is specific for u.v. dimeric photoproducts, but is not mediated by a pyrimidine dimer DNA glycosylase. Instead, it is initiated by a second bona fide endonuclease that may recognize both pyrimidine dimers and pyrimidine-(6-4)pyrimidones. After high doses of ionizing-radiation (e.g. 1.5 Mrad), D. radiodurans can mend > 100 double-strand breaks (dsb) per chromosome without lethality or mutagenesis. Both dsb mending and survival are recA-dependent, indicating that efficient dsb mending proceeds via homologous recombination. D. radiodurans contains multiple chromosomes per cell, and it is proposed that dsb mending requires extensive recombination amongst these chromosomes, a novel phenomenon in bacteria. Thus, D. radiodurans may serve as an easily accessible model system for the double-strand-break initiated interchromosomal recombination that occurs in eukaryotic cells during mitosis and meiosis. PMID- 7984096 TI - A non-directed, hydroxylamine-generated suppressor mutation in the P3 pairing region of the bacteriophage T4 td intron partially restores self-splicing capability. AB - Hydroxylamine (HA) mutagenesis of an HA-induced splicing-defective bacteriophage T4 td intron mutant with a mutation in the intron P3 RNA pairing region was used to generate pseudorevertants. Because HA can only cause GC to AT transitions, the original mutant (H104A) could not undergo true reversion, yet the compensatory mutation on the opposite side of the P3 helix, which was complementary to the original H104A mutation, could occur. A pseudorevertant was isolated that contained both the original H104A mutation and the compensatory mutation HS9. By phenotypic and molecular genetic criteria, this double mutant (H104A-HS9) was shown to be able to undergo significant RNA splicing, thus confirming the existence and functional importance of the long-range P3 pairing region in this phage intron. The second-site suppressor mutation (HS9) was isolated by phage cross and also exhibited some self-splicing ability. A correlation exists between the strength of P3 helix Watson-Crick base pairing and the apparent level of splicing when wild-type, H104A, HS9, and H104A-HS9 are compared. This suggests that the primary role of the P3 RNA pairing region in the T4 td intron is structural in contributing to the critical RNA secondary structure. PMID- 7984095 TI - A conserved DNA sequence is required for efficient gonococcal pilin antigenic variation. AB - Antigenic variation of the Neisseria gonorrhoeae pilus occurs when a variant pilin sequence from a silent locus recombines into the expression locus by predominantly unidirectional, homologous recombination. At the 3' end of all pilin loci lies a conserved DNA sequence, called the Sma/Cla repeat, which has sequence similarity to several recombinase-binding sites, and therefore may be involved in pilin recombination. We have developed a novel reverse transcriptase/polymerase chain reaction (RT-PCR) assay for direct monitoring of pilin recombination, and both RT-PCR and phase variation were used to examine pilin recombination in a gonococcal strain that had had the pilE Sma/Cla repeat removed. Results from these experiments showed a decrease in pilin recombination when the Sma/Cla sequence was deleted from the expression locus, showing that a specialized site (Sma/Cla) is involved in efficient pilin recombination. PMID- 7984098 TI - Structural and functional analysis of the promoter region involved in full expression of the cryIIIA toxin gene of Bacillus thuringiensis. AB - The promoter region of the cryIIIA toxin gene of Bacillus thuringiensis is composed of at least three domains: an upstream region extending from nucleotide positions -635 to -553 (with reference to the translational start codon of cryIIIA), an internal region extending from nucleotide positions -553 to -367, and a downstream region extending from nucleotide position -367 to +18. Deletion analysis and transcriptional fusions to the lacZ gene indicate that full expression of cryIIIA requires the association of the upstream and the downstream region. Primer extension experiments reveal a major cryIIIA transcript (designated T-129) starting at nucleotide position -129 and another transcript (designated T-558) starting at nucleotide position -558. Mutation in the -35 region of the promoter responsible for the initiation of T-558 indicates that the upstream promoter is essential for full expression of cryIIIA, although not sufficient. Deletion of the DNA region carrying the previously described cryIIIA promoter does not affect full expression of cryIIIA and does not modify the 5' end of T-129. Taken together, these results indicate that the 5' end of T-129 is not a trnascriptional start site. Therefore, we propose that T-129 results from the processing of the mRNA initiated at the upstream promoter (T-558), generating a stable mRNA with a 5' extremity at nucleotide position -129. From primer extension analysis and transcriptional fusions to lacZ, it appears that the upstream promoter is weakly but significantly expressed during the vegetative phase of growth, is activated at the onset of sporulation and remains active at least until t5. However, unlike the promoters of other cry genes, this promoter is similar to sigma A-dependent promoters rather than sporulation-specific promoters. This promoter may therefore be transcribed by the E sigma A form of RNA polymerase. Activation at the onset of sporulation could result from the disappearance of a repressor, or the appearance of a stationary-phase-specific activator. PMID- 7984099 TI - The energetics of bacterial growth: a reassessment. AB - The growth yield of microbial cultures can be used to estimate the efficiency of energy generation during a fermentation or respiration. In the past, the assessment of this efficiency in organisms carrying out a respiration has been the subject of many heated debates. This has partly been caused by the complexity of microbial respiratory chains. Strains of Escherichia coli specifically modified in their respiratory chain have been used recently to re-evaluate the energetic efficiency of the bacterial respiration using chemostat cultures. The different strains indeed show different growth efficiencies. The physiological significance of energetically less-efficient branches of the respiratory chain is discussed. PMID- 7984100 TI - The terminal oxidases of Paracoccus denitrificans. AB - Three distinct types of terminal oxidases participate in the aerobic respiratory pathways of Paracoccus denitrificans. Two alternative genes encoding subunit I of the aa3-type cytochrome c oxidase have been isolated before, namely ctaDI and ctaDII. Each of these genes can be expressed separately to complement a double mutant (delta ctaDI, delta ctaDII), indicating that they are isoforms of subunit I of the aa3-type oxidase. The genomic locus of a quinol oxidase has been isolated: cyoABC. This protohaem-containing oxidase, called cytochrome bb3, is the only quinol oxidase expressed under the conditions used. In a triple oxidase mutant (delta ctaDI, delta ctaDII, cyoB::KmR) an alternative cytochrome c oxidase has been characterized; this cbb3-type oxidase has been partially purified. Both cytochrome aa3 and cytochrome bb3 are redox-driven proton pumps. The proton pumping capacity of cytochrome cbb3 has been analysed; arguments for and against the active transport of protons by this novel oxidase complex are discussed. PMID- 7984101 TI - Membrane association and role in DNA uptake of the Bacillus subtilis PriA analogue ComF1. AB - The late competence protein ComF1 is required for genetic transformation in Bacillus subtilis. Because of the sequence similarities of ComF1 to known ATP dependent DNA helicases and translocases, we have hypothesized that this protein either unwinds bound double-stranded DNA or helps in the translocation of the transforming single-stranded DNA across the cell membrane. Two important implications of this hypothesis (the association of ComF1 with the membrane and its specific requirement for DNA uptake) have been tested in this report. Using cell fractionation techniques and Western blotting analysis, we show that ComF1 is located almost exclusively on the cell membrane and that it is membrane targeted independently of other competence proteins. Moreover, ComF1 behaves like an integral membrane protein in extractability and detergent partition assays. We also show that this protein is required for the DNA-uptake step during transformation but not for DNA binding to the cell surface. DNA uptake is blocked in strains with null mutations or in-frame deletions in comF1 but also in strains that overproduce the ComF1 protein under competence conditions. This last observation suggests that ComF1 expression must be balanced with that of other competence proteins, with which it may interact to form a multisubunit complex for DNA uptake. PMID- 7984102 TI - Variable expression of the Opc outer membrane protein in Neisseria meningitidis is caused by size variation of a promoter containing poly-cytidine. AB - Opa proteins of Neisseria meningitidis exhibit translational phase variation via addition or deletion of repetitive coding repeat units within the DNA encoding the protein leader sequence. In contrast, Opc phase variation is the result of transcriptional regulation. Transcription starts 13 nucleotides after the -10 region of an unusual promoter sequence containing a variable number of contiguous cytidine residues and lacking a -35 region. Efficient expression of Opc occurred in strains with 12 to 13 cytidine residues, intermediate expression in strains with 11 or 14 residues and no expression with < or = 10 or > or = 15 residues. This unusual regulation may have evolved because the Opc protein enables meningococcal invasion and is immunogenic. PMID- 7984103 TI - A novel, small endoglucanase gene, egl5, from Trichoderma reesei isolated by expression in yeast. AB - A method is presented for the isolation of genes encoding hydrolytic enzymes without any knowledge of the corresponding proteins. cDNA made from the organism of interest is cloned into a yeast vector to construct an expression library in the yeast Saccharomyces cerevisiae. Colonies producing hydrolytic enzymes are screened by activity plate assays. In this work, we constructed a yeast expression library from the filamentous fungus Trichoderma reesei and isolated a new beta-1,4-endoglucanase gene on plates containing beta-glucan. This gene, egl5, codes for a previously unknown small protein of 242 amino acids. Despite its small size, the protein contains two conservative domains found in Trichoderma cellulases, namely the cellulose-binding domain (CBD) and the linker region that connects the CBD to the catalytic core domain. Molecular modelling of the EGV CBD revealed some interesting structural differences compared to the CBD of the major cellulase CBHI from T. reesei. The catalytic core of EGV is unusually small for a cellulase and represents a new family of cellulases (Family K) and of glycosyl hydrolases (Family 45) together with the endoglucanase B of Pseudomonas fluorescens and the endoglucanase V of Humicola insolens on the basis of hydrophobic cluster analysis. PMID- 7984104 TI - Cloning and molecular characterization of a Legionella pneumophila gene induced by intracellular infection and by various in vitro stress conditions. AB - The synthesis of a global stress protein (GspA) of Legionella pneumophila is induced in the intracellular environment of the phagocytic cell and by various in vitro stress stimuli. We used techniques of reverse genetics to isolate the gspA gene from a genomic library of L. pneumophila. Sequence analysis of approximately 1700 bp of a representative clone (pBSP1) showed the presence of two open reading frames (ORFs). ORF1 encoded for a polypeptide with an inferred molecular mass of 19 kDa and an isoelectric point of 6.1. These predictions correlated with the migration of the GspA protein on two-dimensional SDS-polyacrylamide gels. The predicted amino acid sequence of the GspA protein was identical to 22/23 residues of the N-terminal amino acid sequence derived by Edman degradation of the purified protein. The GspA protein was 41.3% and 36.5% identical to the 16 kDa IbpA and IbpB heat-shock proteins, respectively, of Escherichia coli. Primer extension from mRNA isolated from L. pneumophila showed that transcription of the gspA gene was controlled by two overlapping promoters. One of the promoters was a sigma 70 promoter, while the other was a heat-shock promoter and was regulated by the sigma 32 transcription factor in E. coli. Northern blot analysis showed that the level of gspA mRNA was elevated 3.4-, 5.0-, and 6.7-fold after exposure of L. pneumophila to heat shock, oxidative stress and osmotic shock, respectively. The gspA gene was conserved among 13 serogroups of L. pneumophila. Our data showed that the gspA gene of L. pneumophila, which is induced by intracellular infection and by various stress stimuli, is controlled transcriptionally by two overlapping and separately regulated promoters. PMID- 7984105 TI - The pesticin receptor of Yersinia enterocolitica: a novel virulence factor with dual function. AB - The iron-repressible outer membrane protein FyuA of Yersinia enterocolitica operates as a receptor with dual function: (i) as a receptor for the Y. pestis bacteriocin pesticin, and (ii) as a receptor for yersiniabactin, a siderophore that is produced by mouse-virulent Y. enterocolitica strains of biogroup IB. Cloning of the FyuA-encoding gene was achieved by mobilization of a genomic cosmid library of the pesticin-sensitive and mouse-virulent Y. enterocolitica O:8 strain WA into the pesticin-resistant WA fyuA mutant and subsequent in vivo selection of transconjugants for the ability to survive and multiply in mice (phenotype mouse virulence). The reisolated transconjugants which survived in mice for 3 d harboured a unique cosmid and phenotypically were pesticin sensitive. From this cosmid a 2650 bp SalI-PstI fragment conferring pesticin sensitivity was subcloned. Sequencing of this DNA fragment revealed a single open reading frame of 2022 bp, which encodes a deduced polypeptide of 673 amino acids with a predicted molecular mass of 73,677 Da. Cleavage of a putative signal sequence composed of 22 amino acids should lead to a mature protein of 651 amino acids with a molecular mass of 71,368 Da. The open reading frame is preceded by a sequence which shares homology with the postulated consensus Fur iron-repressor protein-binding site. FyuA shows homology to other iron-regulated TonB-dependent outer membrane proteins with receptor functions (e.g. BtuB, CirA, FepA, IutA, FhuA, FoxA, FcuA). On the basis of multiple alignment of amino acid sequences of FyuA and other TonB-dependent receptors, a phylogenetic tree was constructed, demonstrating that FyuA probably belongs to the citrate subfamily or represents a new subfamily of TonB-dependent receptors. Moreover, by complementation of the WA fyuA mutant by the cloned fyuA gene, yersiniabactin uptake and mouse virulence were restored. These studies demonstrate that the cloned pesticin/yersiniabactin receptor FyuA of Y. enterocolitica has the typical features of iron-regulated TonB-dependent outer membrane receptors for siderophores and bacteriocins and is required for mouse virulence. PMID- 7984106 TI - The dps promoter is activated by OxyR during growth and by IHF and sigma S in stationary phase. AB - Dps is a non-specific DNA-binding protein abundant in starved Escherichia coli cells and is important for the defence against hydrogen peroxide. We found that dps mRNA levels are controlled by rpoS-encoded sigma S, the transcriptional activator OxyR and the histone-like IHF protein. In exponentially growing cells, dps is induced by treatment with hydrogen peroxide in an OxyR-dependent manner. This OxyR-dependent induction occurs only during log phase, although the OxyR protein is present in stationary phase. In the stationary phase cells, dps is expressed in a sigma S- and IHF-dependent manner. The purified OxyR and IHF proteins are also shown to bind upstream of the dps promoter. Our results suggest that the dps promoter is recognized by both sigma 70-holoenzyme and sigma S holoenzyme, since OxyR acts through sigma 70 and the starts of the OxyR- and sigma S-dependent transcripts are identical. PMID- 7984107 TI - Multiple signalling systems controlling expression of luminescence in Vibrio harveyi: sequence and function of genes encoding a second sensory pathway. AB - Density-dependent expression of luminescence in Vibrio harveyi is regulated by the concentration of extracellular signal molecules (autoinducers) in the culture medium. One signal-response system is encoded by the luxL,M,N locus. The luxL and luxM genes are required for the production of an autoinducer (probably beta hydroxybutyl homoserine lactone), and the luxN gene is required for the response to that autoinducer. Analysis of the phenotypes of LuxL,M and N mutants indicated that an additional signal-response system also controls density sensing. We report here the identification, cloning and analysis of luxP and luxQ, which encode functions required for a second density-sensing system. Mutants with defects in luxP and luxQ are defective in response to a second autoinducer substance. LuxQ, like LuxN, is similar to members of the family of two-component, signal transduction proteins and contains both a histidine protein kinase and a response regulator domain. Analysis of signalling mutant phenotypes indicates that there are at least two separate signal-response pathways which converge to regulate expression of luminescence in V. harveyi. PMID- 7984108 TI - Activation of a vmp pseudogene in Borrelia hermsii: an alternate mechanism of antigenic variation during relapsing fever. AB - The relapsing fever agent, Borrelia hermsii, undergoes multiphasic antigenic variation to evade its host's immune response. A frequently observed switch is serotype 7 to 26. Unlike silent vmp genes previously characterized, the transcriptionally silent vmp26 sequence was a pseudogene in lacking a start codon. In serotype 7 the location of the silent vmp26 sequence just downstream of vmp7 on the expression plasmid, as well as on the silent plasmid, was also unique. The demonstration of a predicted circular recombination product in serotype 7 but not serotype 21 populations indicates that the pseudogene was activated by an intramolecular recombination producing a deletion of DNA between 20-nucleotide direct repeats in vmp7 and psi vmp26. PMID- 7984109 TI - Cloning, sequencing, and characterization of multicopy suppressors of a mukB mutation in Escherichia coli. AB - The mukB gene codes for a 177 kDa protein, which might be a candidate for a force generating enzyme in chromosome positioning in Escherichia coli. The mukB106 mutant produces normal-sized, anucleate cells and shows a temperature-sensitive colony formation. To identify proteins interacting with the MukB protein, we isolated three multicopy suppressors (msmA, msmB, and msmC) to the temperature sensitive colony formation of the mukB106 mutation. The msmA gene, which could not suppress the production of anucleate cells, was found to be identical to the dksA gene. The msmB and msmC genes suppressed the production of anucleate cells as well as the temperature-sensitive colony formation. However, none of them could suppress both phenotypes in a mukB null mutation. DNA sequencing revealed that the msmB gene was identical to the cspC gene and that the msmC gene had not been described before. A homology search revealed that the amino acid sequences of both MsmB and MsmC possessed high similarity to proteins containing the cold shock domain, such as CspA of E. coli and the Y-box binding proteins of eukaryotes; this suggests that MsmB and MsmC might be DNA-binding proteins that recognize the CCAAT sequence. Hence, the msmB and msmC genes were renamed cspC and cspE, respectively. Possible mechanisms for suppression of the mukB106 mutation are discussed. PMID- 7984111 TI - Identification and characterization of hitherto unknown Mycoplasma pneumoniae proteins. AB - Eleven hitherto unknown Mycoplasma pneumoniae proteins were identified and characterized with respect to their size and subcellular location. This was carried out through the construction of in vitro gene fusions between a modified mouse dehydrofolate reductase (dhfr) gene and selected regions (cosmid clones) of the M. pneumoniae genome and expressing them in Escherichia coli. Positive clones were identified using antibodies against specific fractions of M. pneumoniae. The deduced protein sequences of 11 out of 30 clones did not show significant homologies to known proteins in protein data-bank searches. Monospecific antibodies against these 11 fusion proteins were used to determine the size and cellular location of the corresponding M. pneumoniae proteins by immunoscreening Western blots of SDS-acrylamide gels from M. pneumoniae cell extracts. PMID- 7984110 TI - The purified SoxABCD quinol oxidase complex of Sulfolobus acidocaldarius contains a novel haem. AB - A respiratory quinol oxidase complex that is encoded by the soxABCD operon has been purified from the thermoacidophilic archaeon Sulfolobus acidocaldarius. The enzyme was solubilized with dodecyl maltoside and purified in the presence of this detergent and ethylene glycol. The complex is hydrodynamically homogeneous and contains at least five different polypeptides. In addition to the major subunits SoxA, SoxB and SoxC, it has two small polypeptides. One of these is the translation product of a short open reading frame (now called the soxD gene) at the end of the operon. The optical and electron paramagnetic resonance spectra of the SoxABCD complex have been characterized. It probably contains four A-type haems which are bound to SoxB and SoxC. The structure of these haems is not identical to haem A. The novel haem As has a 2-hydroxyethyl geranylgeranyl in position 2 of the porphyrin ring whereas haem A has the related farnesyl containing side-chain. PMID- 7984112 TI - Analysis of five tylosin biosynthetic genes from the tyllBA region of the Streptomyces fradiae genome. AB - The tyllBA region of the tylosin biosynthetic gene cluster of Streptomyces fradiae contains at least five open reading frames (ORFs). ORF1 (tylI) encodes a cytochrome P450 and mutations in this gene affect macrolide ring hydroxylation. The product of ORF2 (tylB) belongs to a widespread family of proteins whose functions are speculative, although tylB mutants are defective in the biosynthesis or addition of mycaminose during tylosin production. ORFs 3 and 4 (tylA1 and tylA2) encode delta TDP-glucose synthase and delta TDP-glucose dehydratase, respectively, enzymes responsible for the first two steps common to the biosynthesis of all three deoxyhexose sugars of tylosin via the common intermediate, delta TDP-4-keto, 6-deoxyglucose. ORF5 encodes a thioesterase similar to one encoded in the erythromycin gene cluster of Saccharopolyspora erythraea. PMID- 7984113 TI - Multiplicity of genes encoding secreted aspartic proteinases in Candida species. AB - The secreted aspartic proteinases (SAP) of Candida sp. are presumed to be potential virulence factors. In the opportunistic pathogen Candida albicans the proteinase genes identified to date, SAP1, SAP2, SAP3 and SAP4, constitute a multigene family. Before addressing the possible role of each proteinase in virulence, we sought to isolate all the members of this multigene family by screening a genomic library with a SAP1 probe for additional C. albicans SAP genes using low-stringency hybridization conditions. Three putative new members, SAP5, SAP6 and SAP7 were isolated and sequenced. The N-terminal segments of the deduced amino acid sequences of SAP5 and SAP6 contained secretion signal sequences similar to those of other Candida SAPs. Upon comparison and alignment with the other reported SAP amino acid sequences, SAP7 is not only the most divergent protein but also exhibits a much longer putative pro-sequence with a single Lys-Lys putative processing site. Using SAP1 to SAP7 as probes, the overall number of SAP genes in C. albicans was tentatively estimated by low stringency hybridization to EcoRI-digested genomic DNA. While each isolated SAP gene could be assigned to distinct EcoRI bands, the existence of two additional genes not isolated after screening of the C. albicans gene library was inferred. Furthermore, evidence was obtained for the existence of SAP multigene families in other Candida species such as C. tropicalis, C. parapsilosis and C. guillermondii. PMID- 7984116 TI - Clozapine in three individuals with mild mental retardation and treatment refractory psychiatric disorders. AB - Few investigators have focused on the response of individuals with mental retardation to clozapine. In the general population, some people who have responded to no other psychotropic have had a tremendous positive response, including increased positive scores "quality of life" measures. Clozapine, however, can cause fatal side effects. At least six people in the United States have died from agranulocytosis despite weekly blood counts. The use of clozapine in the general population was reviewed, potential difficulties in prescribing it for individuals with mental retardation discussed, and three relevant case histories presented. PMID- 7984115 TI - A conserved surface-exposed domain in major outer membrane proteins of pathogenic Pseudomonas and Branhamella species shares sequence homology with the calcium binding repeats of the eukaryotic extracellular matrix protein thrombospondin. PMID- 7984114 TI - A copper-transporting P-type ATPase found in the thylakoid membrane of the cyanobacterium Synechococcus species PCC7942. AB - P-type ATPases constitute a large family of cation pumps that play crucial physiological roles in many organisms, including bacteria, plants and mammals. They are postulated to play important roles in a variety of environmental adaptation systems. Recently, we cloned two distinct putative P-type ATPase genes (pacS and pacL) from a photosynthetic cyanobacterium, Synechococcus species PCC7942. In this study, one of the gene products (named PacS) was found to possess a putative metal-binding motif (Gly-Met-X-Cys-X-X-Cys) in its N-terminal portion. Thus we supposed that this ATPase may function as a metal pump. Indeed, the results of Northern blotting analysis showed that pacS-mRNA specifically increases upon addition of copper or silver to the growth medium. The results of Western blotting analysis confirmed the view that PacS accumulates in copper treated Synechococcus cells. Thus we concluded that the expression of PacS ATPase is regulated in response to the change in concentration of external metals, namely copper and silver. Consistent with this, an insertional inactivation mutant of pacS exhibited hypersensitivity in terms of growth to these potentially toxic metals. It was also revealed that PacS was mainly located in the thylakoid membrane, in which the photosynthetic reactions take place. This P-type ATPase in the thylakoid membrane is implicated as a copper-transporting system that may be involved in copper-homeostasis crucial to the photosynthetic thylakoid function. PMID- 7984118 TI - Comprehensive geriatric assessment: applications for community-residing, elderly people with mental retardation/developmental disabilities. AB - The effects of using comprehensive geriatric assessment, a recently developed approach found to be effective in evaluating elderly patients, was explored with 41 community-based elderly individuals with mental retardation/developmental disabilities to determine whether it would reveal a greater number of medical, dental, and psychiatric diagnoses when compared to their previous medical care. Functional status and medication usage of these subjects was assessed and described. Statistically significant increases in the number of medical and dental diagnoses were found. An increased number of psychiatric diagnoses, though not significant, was also found. Results suggest that comprehensive geriatric assessment is useful in the evaluation of the health care needs of individuals with mental retardation/developmental disabilities. PMID- 7984117 TI - Detection of metabolic disorders among selectively screened people with idiopathic mental retardation. AB - Fifth-eight people receiving residential or other services for idiopathic mental retardation were evaluated for evidence of metabolic disease. Five (8%) demonstrated persistent urinary organic acid abnormalities on at least three occasions, which pointed towards specific genetic metabolic defects. Instigation of specific treatment programs may have improved the quality of life for one of these participants. Appropriate genetic counseling was provided but could have been instigated much earlier had these investigations been performed as part of a routine workup for idiopathic mental retardation. This pilot study suggests a need for evaluation of other similar populations with idiopathic mental retardation. PMID- 7984119 TI - Effects on individuals with mental retardation of changing Depakote to Depakene. AB - This study was conducted to determine whether Depakene could be substituted for Depakote, which would represent a significant financial savings, without sacrificing symptom control or drug tolerance. Over an 8-week period of intensive monitoring, we changed 77 patients from Depakote to Depakene. Results showed no change in seizure control, no adverse upper gastrointestinal side effect, no weight change, no sleep disturbance, no change in aberrant behavior, and no change in appetite. Patients were less less lethargic on Depakene than on Depakote. However, there was some increase in diarrhea, of uncertain cause. Some changes in psychiatric symptoms were also noted. Overall, this drug change was well-tolerated. PMID- 7984120 TI - Development and psychometric analysis of an indirect measure of attitudes toward individuals with mental retardation using the error-choice method. AB - The Test of Knowledge About Mental Retardation consists of 20 error-choice items requiring respondents to select one of four incorrect alternatives. The true purpose of the test (measurement of attitudes) is disguised by the inclusion of 20 items of general knowledge about mental retardation. Analyses of data indicated satisfactory item characteristics, adequate reliability and homogeneity, and preliminary support for criterion-related validity. The test should be useful for investigating the attitudes of service providers whose responses to a questionnaire may be biased by respondent sensitization and social desirability responding. PMID- 7984121 TI - Quality care for individuals with dual diagnosis: the legal and ethical imperative to provide qualified staff. AB - An evaluation of the treatment and habilitation services being provided to individuals with dual diagnoses of mental retardation and mental illness was presented. The current status of service delivery is identified as unacceptable. Legal issues relating to the obligation to provide quality services were discussed as were ethical issues relating to where the responsibility for providing such service lies. General ethical principles of nonmaleficence and beneficence were defined, and the codes of ethics for two professional groups were invoked to bolster the position that administrators and supervisors are ultimately responsible for the quality of service provided by their organizations. Recommendations for staff competencies necessary to improve treatment for individuals with dual diagnosis were made. PMID- 7984122 TI - On "good" terms: labeling people with mental retardation. PMID- 7984123 TI - Commentary on Wolfensberger (1994). PMID- 7984124 TI - Comments on "Sexology and social work in a case of Klinefelter (47,XXY) syndrome". PMID- 7984125 TI - Quality assurance in an era of consumer empowerment and choice. PMID- 7984126 TI - Quality of care, quality of life: a rural perspective. PMID- 7984127 TI - Thoughts on the police interrogation of individuals with mental retardation. PMID- 7984128 TI - Trends and milestones. PMID- 7984129 TI - [Precancerous conditions of the oral cavity. Note I. General considerations. Critical review of the literature]. AB - The authors deal with the current topic of precancerous states of the oral cavity, considering various aspects such as etiopathology, diagnosis, the clinical picture and therefore, nosological classifications. The region of the Air Passages and Superior Digestive Tract (APSDT) should be considered as a single system and it is affected by a set of genetic and environmental conditions common to the various anatomical regions of which it consists. The significance of several irritating agents, which are also habitually used (e.g. tobacco), has been demonstrated for some time, whereas, the actual harmful effects of other factors such as immunodepression in particular, are only now being evaluated and detected. The discussion concerning precancerous lesions of the oral cavity, should actually refer to lesions that do not present the histologic, biological and clinical characteristics of malignant neoplasms, but that have the objective possibility of developing them. Some lesions that traditionally belong to this pathological grouping often present dysplastic aspects, if not the actual characteristics of "carcinoma in situ". Therefore, the availability of a set of indexes is of primary importance and it should be capable of providing an orientation for diagnosis and clinical practices in a precise, standardized manner. The authors hold these indexes to be divisible into three groups as follows. The first group is composed of the "parameters of cellular kinetics" and includes the percentage of cells in phase S (LI), phase S time (Ts), cell cycle duration (Tc), and the growth fraction (GF). The second group consists in the "parameters of cellular morphology", including the nuclear content in DNA, the value of the nuclear surface and the ploidy. The third group is more specific for the existence of a pathologic mass. However, given the uncertainties of the borderlines traditionally attributed to precancerous pathology, this group is definitely useful. It is composed of the potential doubling time (Tpot) and the tumor volume doubling time (Td). Moreover, biopsy is held to be an indispensable tool and the procedure should be conducted in the various manners possible according to well-defined conditions. A correct evaluation of these parameters allows for a correct approach to precancerous pathology and the prevention of the clinical risks of "rapid proliferation" even in the diagnostic biopsy phase. PMID- 7984131 TI - [Relationship between nevus and melanoma. Review of the literature]. AB - The main purpose of this paper is to explain the development of the thought and the most updated considerations about the correlations between nevi and melanoma, through a critical review in chronological order of the scientific publications about it since 1969. This leads to the discussion, correction and recovery of thoughts that had been left. In fact we know that a kind of correlation exists but, until now, has not been completely explained. PMID- 7984130 TI - [Precancerous conditions of the oral cavity. Note II--Pathology and clinical course. Critical review of the literature]. AB - The authors examine some specific forms of precancerous states of the oral cavity, selecting them from among the 4 classes defined by the WHO Collaborating Centre for Oral Precancerous Lesions. The immunological system is given particular emphasis. In fact, as studies progress, it appears to be more and more involved not only in the increase in the incidence of such pathologies, but also in the most difficult, if not unknown, genesis of these pathologies. Highly significant examples of this involvement are: Kaposi's Sarcoma, Hairy Cell Leukoplakia, Lichen and Mycoses. Particularly significant aspects for Erythroplasia consist in the following: slow development, frequent and rapid changes in the clinical aspects and its strict connection with Bowen's Disease and Queirat's Erythroplasia. The latter lend further confirmation of its definite precancerous nature and as such, it requires radical surgical treatment. Compared to other forms, the Epidemic variety of Kaposi's sarcoma more frequently affects the oral-salivary glands and structures, the lymph nodes and the laterocervical area. Together with non-Hodgkin tumors, this represents the class of neoplasms most frequently occurring in subjects affected by AIDS. Its "atypical" aggressiveness involves the liver and pancreas and develops over much shorter time periods than the other varieties. In any case, when possible, the treatment required is the excision of the lesions. Neither radiation therapy nor polychemotherapy have yielded encouraging results as yet. In the case of Leukoplakia, it should be kept in mind that today, this pathology is defined "negatively" be exclusion that is the condition must exist that this lesion cannot be clinically or pathologically defined as another lesion. It thus follows that the clinician must maintain an extremely cautious approach in such cases. As concerns prognosis, particular attention should be given to raised, hardened, irregular and fissured forms, which manifest the greatest degenerative capacity. for the classic forms, the treatment adopted is complete exeresis, whereas the use of antiviral drugs is recommended for Hairy Cell Leukoplakia. Lichen Ruber Planus is a papuliferous eruption that is relatively common and affects the skin and mucosa often exclusively involving the oral cavity in the great majority of cases. Besides the clinical picture, the diagnosis of this disease is based on the triad consisting of hyperkeratosis, destruction of the cells of the stratum basale and subepithelial lymphocyte infiltration at distinctly low levels. In uncertain cases, however, the detection of Fluorescent Bodies grouped in large clusters near the hyaline membrane, acquires particular importance for the specification of the diagnosis. PMID- 7984133 TI - [Deep rotated connective tissue flap for the reconstruction of the interdental papilla]. AB - The LCPR or Rotated Connective Flap is a simple mucogingival surgery technique that permits the to recreate, of an interdental papilla by the contribution of the vascularized connective pedicle. Keeping a good vascularization of the flap by its pedicle and its good recovering by some superficial flaps, seems to insure a long dated stability of the reconstruction. PMID- 7984132 TI - [Fractures of maxillo-facial bones in children. Our experience]. AB - A clinic-statistical study of maxillo-facial fractures in a series of 52 children is reported. This group presents a higher involvement of mandibular body and a low rate M:F than in the literature. Factors responsible for increasing of maxillo-facial traumas in little girls and in school age are analyzed. PMID- 7984134 TI - [Gorlin-Goltz syndrome with odontogenic keratosis. Report on a patient followed for 10 years]. AB - A patient with Gorlin-Goltz syndrome (nevoid basal cell carcinoma syndrome) is described. This disease has an autosomal dominant inheritance pattern with complete penetrance and extremely variable expressivity. The case report seems to represent a new mutation. Gorlin-Goltz syndrome is characterized by a lot of symptoms primarily involving the skin, central nervous system, and skeletal system. In 90% of the patients, nevoid basal cell carcinoma syndrome is associated with recurring odontogenic keratocysts. Also our patient showed recurrent jaw and maxillary cysts, for this reasons he has been followed for 10 years to the Oral Pathology Service of Galliera Hospital. PMID- 7984135 TI - [Surgical treatment of hemangioma of bones of the orbito-zygomatic region]. AB - The incidence of intraosseous haemangiomas is very low. The mandible, the zygoma, the maxilla and the frontal bone are the most frequent areas of localization in the craniomaxillofacial region. Pain and swelling are the most important symptoms of these tumors when they are localized in the orbit or in zygoma. Surgery, without preoperative embolization is always the best treatment for intraosseous haemangiomas of the zygoma. The radical removal of the tumor frequently causes a plain aesthetical loss which has to be restored. Calvarial grafts are a good solution to the problem of reconstruction of bone loss. They are easy to prepare, near to the implant zone, and they don't need changes of the patient's position during the operation. The implants fixed by mini- and micro-fixation systems provide a good functional and aesthetical result. The authors, after a review of the literature about intraosseous haemangiomas of the cranio-maxillofacial region, report two cases of intraosseous haemangioma of the zygoma in which removal of the tumor and reconstruction with calvarial grafts has been performed. PMID- 7984136 TI - [Event-related potentials and language processing]. AB - The contribution of cognitive event-related potentials (ERPs) and particularly of the N400 component to the study of language processing is considered. After a general presentation of the various components of cognitive evoked potentials which are differentiated from early potentials (sensitive to perceptive parameters), the neurophysiological and psychological correlates of ERPs are discussed. Before the presentation of the main studies concerned with the correlation between specific late components and linguistic processes, it is proposed an introduction to some theoretical models of language processing which serve as conceptual framework supporting most of the experimental approaches in this field. The results of EPs studies devoted to functional asymetries in language processing are briefly mentioned. Then a number of studies are analysed, these demonstrate the sensitivity of event-related potential measures to linguistic manipulations. Finally, the studies concerned with the N400 are reviewed, this potential appears to be the more specifically language-related ERP component, even if its connection with specific linguistic processes or its differentiation from N200 are still under debate. Nevertheless language-related electrophysiological investigations may become in the near future a useful complementary approach to our understanding of language processing and language disorders. PMID- 7984137 TI - [EEG spike focus topography: study of potential fields]. AB - Mapping study of EEG spike focus was performed on 122 topographic maps, from 88 records of 72 subjects, classified in: F for "functional" (no epileptic seizure); EGI, EGS and EGC: respectively generalized idiopathic, symptomatic and cryptogenic epilepsies; EPI, EPS and EPC: respectively partial idiopathic, symptomatic and cryptogenic epilepsies--epilepsies with centro-temporal spikes (EPR) are predominant in this group--; EI: indeterminate epilepsies. The graphoelements study: morphology, localization, amplitude, time course (sites of appearance, culmination and disappearance) and of electrical fields: distribution, monopolar, bipolar or intermediary aspect was performed. In order to quantify the brain mapping data we established series of numeric parameters: maximal negative and positive values; sum of the negative and positive values; ratio of these values. EGS and EPS groups have very variable map imaging for a patient or from a patient to another, r1 ratio is lower to 0.33. Idiopathic epilepsies are characterised by the stability of imaging, in the EGI group aspect is frequently monopolar with a central negativity, r1 and r2 ratios are high (0.9 and 1.2); in the EPI group the aspect can be monopolar or bipolar, in the EPR the aspect is stable, longitudinal bipolar, r1 and r2 ratios are between 0.33 and 0.99. In the EGC, EPC and EI groups there is no typical imaging, the mapping aspect can be monopolar or bipolar, in EGC and EPC r1 ratio is between 0 and 0.99, in EI r1 and r2 ratios are low (r1 = r2 = 0.2). In the F group the monopolar aspect is frequent. We can note the stability of the electrical fields apportionment in idiopathic epilepsies which is explainable by the integrity of the cerebral potential propagation pathways in spite of a dysfunction responsible of the epileptic seizures, the presence of a lesion is one of the responsible factors of the instability of the brain mapping. PMID- 7984138 TI - Giant somatosensory evoked potentials and pathophysiology of hyperekplexia. Neurophysiological study of one patient. AB - EEG during wakefulness and sleep and somatosensory evoked potentials from the median nerve were recorded in a 3 year-old boy with hyperekplexia and his close relatives (parents and two sisters). Centro-temporal spikes during sleep were found in the patient and in the older sister, while somatosensory evoked potentials, in the patient, showed abnormally high amplitude over the centroparietal regions. Pathophysiological mechanisms of hyperekplexia are discussed and the existence of symptomatic forms is suggested. PMID- 7984139 TI - [Study of the proximal conduction of the arms using SEP and MEP]. AB - The proximal conduction of the upper limb has been studied with the somatosensory evoked potentials (SEP) and motor evoked potentials (MEP) in 40 controls which provided normal data. The SEP allowed the sensory conduction study of the Erb/C7 segment with N9/N13 delay determination after the median nerve stimulation at the wrist, and after the ulnar nerve stimulation at the wrist (20 cases) or above the elbow (20 cases). The N9/N13 delay was 3.24 ms +/- 0.35 for the median nerve, 3.30 ms +/- 0.52 for the ulnar nerve after stimulation at the wrist and 3.30 ms +/- 0.40 after stimulation at the elbow. The Erb point potential amplitude after ulnar nerve stimulation at the elbow was always greater than after the median nerve stimulation at the wrist: 13.2 microV versus 8.8 microV. The MEP allowed the C6/axilla motor conduction study. The recording was performed on the adductor digiti quinti. The proximal motor conduction velocity was 74 m/s +/- 8 (mini 60). The conduction delay was then 3.02 ms +/- 0.3. A constant amplitude loss was observed between the axilla and the cervical spine; it was never greater than 30% in controls. Allthings considered both methods provided very complementary data on the proximal nerve conduction of the upper limb at the brachial plexus. The conduction delay in the brachial plexus was around 3 ms and was very similar to the distal motor and sensory latencies of the median nerve at the wrist. Motor conduction blocks of more than 30% and 1 ms increament of the conduction delay were regarded as pathological. PMID- 7984140 TI - Deaths resulting from residential fires--United States, 1991. AB - Most residential fires occur during December through March--a period of colder weather and longer darkness. During 1991, residential fires were the second leading cause of injury deaths (after motor-vehicle-related injuries) among children aged 1-9 years and the sixth leading cause of such deaths among persons aged > or = 65 years. Because of seasonal variations in the occurrence of residential fires, CDC analyzed death certificate data from U.S. vital statistics mortality tapes maintained by CDC's National Center for Health Statistics and data from the National Fire Incidence Reporting System (NFIRS) to improve characterization of selected residential fires. This report summarizes the analysis of death certificate data for 1991 and data from NFIRS for 1990. PMID- 7984141 TI - Infant mortality--United States, 1992. AB - The final infant mortality (death before age 1 year) rate for the United States for 1992-8.5 infant deaths per 1000 live-born infants--was the lowest rate ever recorded and represented a decrease of 4.5% from the rate of 8.9 for 1991 (Figure 1). Based on provisional data, the trend in declining infant mortality continued through 1993 (rate: 8.3). This report characterizes infant mortality in 1992 using information from birth and death certificates compiled by CDC's National Center for Health Statistics and compares findings with those for 1991. PMID- 7984142 TI - Mortality patterns--United States, 1992. AB - In 1992, a total of 2,175,613 deaths were registered in the United States--6095 more than in 1991 and the most ever recorded in one year . Despite this increase, the overall age-adjusted death rate (504.5 per 100,000 population) was the lowest ever recorded. In comparison, provisional data indicate that the overall rate increased in 1993. This report summarizes an analysis of final mortality data for 1992 and compares patterns with 1991. PMID- 7984143 TI - Update: respiratory syncytial virus activity--United States, 1994-95 season. AB - Respiratory syncytial virus (RSV), a common cause of winter outbreaks of acute respiratory disease, causes an estimated 90,000 hospitalizations and 4500 deaths each year from lower respiratory tract disease in both infants and young children in the United States. Outbreaks occur annually throughout the United States, and community activity usually peaks within 1 month of the national peak. RSV activity in the United States is monitored by the National Respiratory and Enteric Virus Surveillance System (NREVSS), a voluntary, laboratory-based system. This report presents provisional surveillance results from the NREVSS for RSV during July 2-December 9, 1994, and summarizes trends in RSV from July 1, 1990, through July 1, 1994. PMID- 7984144 TI - DNA sequence specificity of the v-erb A oncoprotein/thyroid hormone receptor: role of the P-box and its interaction with more N-terminal determinants of DNA recognition. AB - The viral erb A oncogene is a mutated allele of a normal cell gene for a thyroid hormone receptor. The DNA recognition properties of the v-erb A protein are altered from those of the thyroid hormone receptor, due in part to a point mutation in the P-box of the zinc-finger domain of the viral allele. We report here the effects of systematically varying this P-box codon; our results suggest that this P-box amino acid contributes to DNA specificity not by promoting recognition of the appropriate response elements, but rather by excluding binding of the erb A protein to inappropriate half-sites. In this manner, DNA recognition by the v-erb A protein appears to differ from that by the glucocorticoid receptor. A variety of P-box amino acids were compatible with recognition of the prototypic AGGTCA half-site; intriguingly, several of these mutant erb A proteins could also recognize a variety of alternative half-site sequences. Recognition of these alternative half-sites required a compatible amino acid sequence in the N terminus of the erb A protein. Our results begin to define a code by which the identity of the amino acids in the zinc-finger and N-terminal domains is reflected in the DNA recognition properties of the receptor. PMID- 7984145 TI - The effects of P-box substitutions in thyroid hormone receptor on DNA binding specificity. AB - Three "P-box" amino acids within the DNA recognition alpha-helix of members of the steroid hormone and thyroid hormone families of nuclear receptors are known to determine the identity of two of the six base pairs within the half-sites of cognate DNA elements. We introduced P-box substitutions derived from different members of the thyroid hormone/estrogen receptor (T3R/ER) family into the beta isoform of human thyroid hormone receptor (hT3R beta) and tested the DNA binding and transactivation activities of these mutants using thyroid hormone response elements (TREs) with half-sites composed of different sequences and arranged in different orientations. Different P-box sequences derived from the T3R/ER family resulted in distinct DNA binding specificities determined by the fourth base pair of the half-site. Thyroid hormone receptor mutants containing EGA, EAA, EGS substitutions for the wild type EGG P-box bound with wild type affinity to consensus AGGTCA half-sites, regardless of orientation. TREs composed of AGGACA half-sites bound hT3R beta s with an EGG or EAA P-box sequence, but not those with EGA or EGS P-box sequence. A reversal of this specificity was observed on a direct repeat TRE with AGGGCA half-sites. Additionally, an ESG P-box substitution in hT3R beta prevented the receptor from binding to a direct repeat as a homodimer, but this mutant could bind as a heterodimer with retinoid X receptor or to the everted repeat TRE from the chicken lysozyme promoter. PMID- 7984146 TI - Divergent dimerization properties of mutant beta 1 thyroid hormone receptors are associated with different dominant negative activities. AB - Syndromes of resistance to thyroid hormones are caused by mutations in the T3 binding domain of the c-erbA beta thyroid hormone receptor gene. The S receptor (deletion of THR332) is a potent dominant negative protein cloned from a kindred with generalized resistance to thyroid hormones. The G-H receptor (ARG311HIS) has compromised dominant negative function and was found in both normal individuals and in a patient with severe pituitary resistance to thyroid hormones. We have investigated the mechanism responsible for the difference in receptor phenotypes by analyzing the binding of S and G-H receptors to thyroid hormone response elements with electrophoretic mobility shift analysis. Wild-type human c-erbA beta 1 (WT), S, and G-H receptors were synthesized in reticulocyte lysate, reacted with a thyroid hormone response element consisting of a direct repeat with 4 base pairs (DR+4; AGGTCA CAGG AGGTCA), and the products analyzed by gel shift. G-H receptor homodimerization was greatly impaired; G-H formed predominantly monomeric complex compared with monomeric and homodimeric WT complexes. The G-H receptor was able to form heterodimeric complexes with cellular thyroid hormone receptor auxiliary protein (TRAP) factors including the human retinoid X receptor-alpha. When TRAP was limiting, the levels of G-H heterodimeric complex were 2- to 3-fold reduced compared with WT receptor. In contrast to the WT and G-H receptors, the S receptor formed almost exclusively homodimeric complex with DR+4; the approximate ratio of S:WT:G-H homodimeric complexes at equivalent concentrations of receptors was 60:20:1. A measurable increase (1.2- to 2.6-fold) in heterodimeric complex formation was observed with the S receptor relative to WT when TRAP was at limiting concentration. As reported previously by others, thyroid hormone significantly reduced the WT homodimeric complex with DR+4. There was no effect on the S homodimeric complex. Finally, the WT, S, and G-H receptors formed different complexes with the element consisting of an inverted repeat with 5 base pairs (IR+5; AGGTCA ACAGT TGACCT) and the IR element (AGGTCA TGACCT), which were differently regulated by thyroid hormone. The S receptor bound as a homodimer with IR+5, whereas the WT receptor bound as a homodimer only with thyroid hormone. No homodimeric complex formed with IR+5 and the G-H receptor. Qualitatively similar results were observed with the IR element. We conclude that the ARG311HIS mutation severely perturbs the homodimerization and, to a much less degree, heterodimerization functions of the c-erbA beta 1 receptor. Furthermore, the THR332 deletion mutation augments homodimerization of the c-erbA beta 1 receptor. These results indicate that different mutations in the c-erbA beta 1 thyroid hormone receptor have divergently affected dimerization activities which seem to influence the level of dominant negative activity in man. PMID- 7984147 TI - Identification and characterization of an antisense RNA transcript (gfg) from the human basic fibroblast growth factor gene. AB - Basic fibroblast growth factor (bFGF) is an autocrine growth factor that is overexpressed in glial tumor cells and promotes their unregulated proliferation. We have previously reported that increased messenger RNA (mRNA) stability contributes to the elevated steady state levels of bFGF mRNA in human U87-MG glioma cells. Stability of bFGF mRNA is regulated by a natural antisense transcript in Xenopus oocytes, but the mammalian equivalent of this transcript has not previously been described. We were interested in identifying the human equivalent of this antisense transcript in order to study its role in bFGF mRNA stability. Analysis of the 3'-untranslated region of the 6.7-kilobase human bFGF mRNA revealed two areas of greater than 75% homology to exons 3 and 4 of the Xenopus antisense transcript, separated by 4300 basepairs of nonhomologous sequence. We used reverse transcription-polymerase chain reaction to amplify, clone, and sequence a 301-basepair fragment of the antisense splice variant from U87-MG cells. The clone (gfg-1) is 73% identical to the Xenopus sequence, with a conserved splice junction and an open reading frame. Strand-specific gfg-1 complementary RNA probes detect a 1.5-kilobase mRNA transcript in normal rat tissues and human T47D breast cancer cells, which contain very low levels of bFGF mRNA. In contrast, antisense transcript expression was undetectable by Northern hybridization in U87-MG cells, which overexpress the bFGF sense mRNA. The reciprocal relationship between bFGF sense and antisense expression suggests that antisense transcripts may regulate bFGF expression in mammalian cells, and that disruption of normal sense/antisense mRNA ratios may lead to overexpression of bFGF in some tumors. PMID- 7984148 TI - Activation of the progesterone receptor by the gonadotropin-releasing hormone self-priming signaling pathway. AB - Signal amplification is fundamental to the normal operation of the preovulatory LH surge and is achieved through processes such as GnRH self-priming and augmentation of stimulated LH secretion by progesterone. We have proposed a model for GnRH self-priming that requires cross-communication between a GnRH receptor activated protein kinase A pathway and the progesterone receptor (PR) to achieve amplification of the GnRH signal. We found that a pulse of GnRH administered to gonadotrope-enriched pituitary cells cultured in medium containing charcoal treated serum plus estradiol (E2) potentiated the LH secretory response to subsequent GnRH pulses, and this potentiation could be blocked by a PR antagonist, RU486, in the absence of progesterone. Similarly, exposure of gonadotrope-enriched cultures to forskolin augmented the response to a pulse of GnRH, and the augmentation due to cAMP elevation could be reduced by RU486 in the absence of progesterone. To directly test whether stimulation with either GnRH or a cAMP analog results in transactivation of the endogenous PR, we used rat anterior pituitary cells cultured in the presence of E2 and transfected with reporter plasmids containing progesterone-responsive elements (PRE) and either a E1b or a thymidine kinase (tk) promoter linked to the chloramphenicol acetyltransferase (CAT) gene. For pituitary cells transfected with the PRE-E1b CAT plasmid, exposure to either progesterone, GnRH, or 8-bromo-cAMP (8BrcAMP) for 6 h resulted in an induction of CAT activity which could be suppressed by coincubation with RU486. RU486 by itself had no effect on CAT activity. Similar results were obtained when a plasmid containing a different promoter (PRE-tk-CAT) was used. For cells transfected with a construct lacking a PRE (pSV2CAT), 8BrcAMP was without effect on CAT expression. When cells were made PR-deficient by omission of E2 from the incubation medium and transfected with PRE-E1b-CAT, neither progesterone, GnRH, nor 8BrcAMP was able to induce CAT activity. In summary we found that either GnRH or 8BrcAMP is able to stimulate transcription of reporter genes linked to two different PRE-containing promoters in anterior pituitary cells that contain endogenous PR; this occurred in the absence of progesterone and was suppressed by a PR antagonist. A simple interpretation of these data is that a GnRH-triggered signaling cascade can result in progesterone independent transactivation of the PR. We propose that, in the normal operation of the preovulatory LH surge, the pathways for GnRH self-priming and progesterone augmentation converge at the PR and that the pathways serve as physiological redundancies to ensure the LH surge. PMID- 7984149 TI - Sensitive and specific detection of retinoid receptor subtype proteins in cultured cell and tumor extracts. AB - Subtype-specific antipeptide antibodies have been developed against each of the retinoic acid receptors (RARs alpha, beta, and gamma) and each of the retinoid X receptors (RXRs alpha, beta, and gamma). Each antibody reacts specifically with its respective recombinantly expressed protein but not with any of the other retinoid receptor subtypes, by both immunoblot and immunoprecipitation technology. We describe a sensitive and specific assay that combines the binding of cultured cell and tumor extracts to [3H]all-trans-retinoic acid or [3H]9-cis retinoic acid with immunoprecipitation of the hormone-receptor complexes by the subtype-specific antibodies to determine the levels of functional retinoid receptor subtype proteins that are present. We also report the use of a hormone binding assay that uses RAR- and RXR-selective compounds as competitors of the tritiated retinoids to ascertain the RAR and RXR subfamily profiles of these cells. HeLa cells contain all six retinoid receptor proteins ranging in concentration from 9 fmol/mg total protein for RAR beta and RXR gamma to 50 fmol/mg for RXR alpha. Hep G2 and HL60 cells express RAR alpha and RXR alpha proteins at approximately 20-60 fmol receptor/mg protein, and RAR beta is expressed at lower levels (approximately 5 fmol/mg) in Hep G2 cells. MCF-7 cells in culture express RAR alpha (approximately 32 fmol/mg), RAR gamma (approximately 35 fmol/mg), and RXR alpha (approximately 60 fmol/mg).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7984150 TI - An extracellular congenital nephrogenic diabetes insipidus mutation of the vasopressin receptor reduces cell surface expression, affinity for ligand, and coupling to the Gs/adenylyl cyclase system. AB - The mutation of the type-2 vasopressin receptor (V2R) apparently responsible for X-linked congenital nephrogenic diabetes insipidus (CNDI) in the Q3 family consists of a T to C transition in codon 113, causing the change of Arg-113 to Trp. Arg-113 is located in the putative first extracellular loop of the V2R next to a frequently conserved Cys thought to interact via a disulfide bridge with a Cys of the second extracellular loop. The present study explored whether this mutation may account for the CNDI phenotype. The mutation was excised from the genomic DNA of a Q3 patient and introduced into the V2R cDNA, which was then placed into an expression plasmid and transfected into COS cells for transient expression and murine L cells for stable expression. Studies with L cells expressing similar levels of wild type and Q3 receptors showed that the mutant receptor has a 20-fold reduced affinity for arginine vasopressin (AVP) and stimulates adenylyl cyclase with an EC50 that is increased by a factor of about 60-fold. The same shift in the EC50 for adenylyl cyclase stimulation was obtained when deamino[8-D-Arg]vasopressin was substituted for AVP. Studies with COS cells revealed that at equal levels of transfected DNA, the mutant receptor is expressed at lower levels (about 20%) than the wild type receptor, indicating that the mutation hinders the transport of the receptor to the cell membrane.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7984151 TI - The cyclic adenosine 3',5'-monophosphate- and the glucocorticoid-dependent enhancers are targets for insulin repression of tyrosine aminotransferase gene transcription. AB - The pathway of gluconeogenesis is activated in liver shortly after birth and is controlled by glucagon and glucocorticoids, which stimulate, and insulin, which inhibits, the expression of genes coding for gluconeogenic enzymes. To understand the molecular basis of this cell type-specific and coordinate control, we analyzed the cis-regulatory elements of the tyrosine aminotransferase gene, which confer liver cell-specific expression in dependence of these hormones. The cAMP responsive element (CRE) of the TAT gene is an essential element within a liver specific enhancer and is recognized by the CRE-binding protein (CREB) in a phosphorylation-dependent manner. The glucocorticoid response is mediated by a complex regulatory unit comprised of the glucocorticoid receptor and other transcription factor-binding sites. Here, we show that both the cAMP- and glucocorticoid-inducible enhancers are targets for the antagonistic effects of insulin. The insulin-responsive sequences coincide with the CREB-binding site of the cAMP-responsive enhancer and a hepatocyte nuclear factor-3-binding site within the glucocorticoid-responsive unit. This design of the hormone-dependent enhancers reflects the molecular mechanism underlying the onset of tyrosine aminotransferase expression at birth when insulin levels decrease and concentrations of glucagon and glucocorticoids increase. PMID- 7984152 TI - Insulin-like growth factors activate estrogen receptor to control the growth and differentiation of the human neuroblastoma cell line SK-ER3. AB - The neuroblastoma cell line SK-ER3, which is stably transfected with the estrogen receptor (ER), was used to study the effect of insulin and insulin-like growth factors (IGF-I and IGF-II) on growth and morphological differentiation induced by estrogens. The data demonstrate that insulin and related growth factors control the growth and morphological differentiation of the cell line expressing the ER, but not of the parental cell line. Effects elicited by the growth factors in SK ER3 cells can be blocked by ER antagonists. Transient transfection studies further confirm an effect of the IGFs in modulation of ER-activated promoters. The results presented support the hypothesis of the existence of cross-talk between membrane and intracellular receptors and provide evidence for physiological consequences of the activation of such a pathway of communication. The present study is of particular interest with regard to the theory of prenatal involvement of the ER in maturation of nerve cells. It could, in fact, be hypothesized that IGF-I and IGF-II, present in high concentrations in the developing brain, might activate the ER expressed in several embryonic brain nuclei. PMID- 7984153 TI - Human luteinizing hormone and chorionic gonadotropin are targeted to a regulated secretory pathway in GH3 cells. AB - LH is a dimeric glycoprotein hormone that is stored in the anterior pituitary and is released in response to GnRH, while the placental hormone, human CG (hCG), sharing the same alpha-subunit and a related beta-subunit, is secreted constitutively. In search of a determinant that allows sorting of LH into a regulated secretory pathway, the genes encoding the common alpha- and LH/CG beta subunits were expressed in the GH3 rat pituitary tumor cell line, which contains a regulated secretory pathway. Steady state labeling and subsequent chase experiments showed that not only LH but also hCG can be sorted to a regulated secretory pathway; after an initial period of constitutive secretion, the mature forms of both hormones containing processed oligosaccharides were stored intracellularly, and their release was stimulated by either forskolin or KCl depolarization. In Chinese hamster ovary cells, which lack a regulated pathway and are devoid of storage granules, only hormones containing unprocessed N-linked oligosaccharides were found. In GH3 cells the LH beta-subunit was partially retained in an endoglycosidase H-sensitive form, presumably in the endoplasmic reticulum; the enzyme-resistant fraction was secreted through a regulated secretory pathway. A large fraction of the hCG beta-subunit was released constitutively, although some mature hCG beta-subunit accumulated in secretory granules and was released by forskolin. The common alpha-subunit was secreted constitutively with little intracellular accumulation of the mature forms. We conclude that the LH beta-subunit contains sufficient information to direct LH to a regulated pathway, and alpha:LH beta assembly is not a prerequisite for this targeting. The sorting of hCG to a regulated pathway in GH3 cells presumably reflects a structural similarity between LH and hCG. In addition, we have shown that GH3 cells can recognize the N-linked oligosaccharides on the gonadotropin subunits as substrates for sulfation. PMID- 7984154 TI - Pax-QNR/Pax-6, a paired box- and homeobox-containing gene expressed in neurons, is also expressed in pancreatic endocrine cells. AB - After differential screening of a cDNA library constructed from quail neuroretina cells infected with the v-myc containing avian retrovirus MC29, we have isolated a cDNA clone Pax-QNR, homologous to the murine Pax6 which is mutated in the autosomal dominant mutation small eye (Sey) of the mouse and aniridia in man. Here we report the characterization of Pax-QNR/Pax-6 expression in the chicken, quail, and mouse pancreas. In situ hybridization performed with E3 chick embryos demonstrated that, in addition to the documented expression of Pax-QNR/Pax-6 in the neural tube, this gene is also expressed in the pancreatic bud. This expression is later restricted to discrete parts of the organ. From bacterially expressed Pax-QNR peptides we obtained rabbit antisera (paired domain, serum 11; domain between paired and homeo, serum 12; homeodomain, serum 13; and carboxyl terminal part, serum 14) capable of specifically recognizing Pax-QNR/Pax-6 proteins (48, 46 kilodaltons) in cell lines derived from alpha- and beta pancreatic cells, but not from exocrine derived cell lines. We conclude that Pax QNR/Pax-6 represents another gene expressed both in the endocrine pancreas and neuro-ectodermic tissues. PMID- 7984155 TI - Psychophysiological correlates of emotion regulation. Introduction. PMID- 7984156 TI - Adrenocortical activity and emotion regulation. AB - Activity of the HPA system does appear to be related to emotion regulation processes in children. The conditions known to modulate HPA activity in animals, adults, and children correspond well to the behavioral strategies often discussed in the domain of emotion regulation. Individual differences in emotion processes related to negative emotion temperaments appear to be associated with individual differences in HPA reactivity among normally developing children, with both fearful, inhibited temperaments and distressed, angry temperaments being associated with greater HPA reactivity. Among children exhibiting behavior problems in the clinical range, however, it may be the "internalizing" patterns that are associated with greater HPA reactivity. The body of research concerning the psychobiology of the HPA system strongly suggests that associations between emotion regulation styles and HPA activity are not merely correlations, that they do indeed reflect potential causal connections. HPA activation and regulation has been shown in animals both to influence and to be influenced by emotions and their corresponding behavioral and psychological processes. Despite a reasonable body of research that now exists on children, many questions regarding the relations between HPA activity and emotion processes remain to be examined. In addressing these questions, it may be useful to consider several periods of the HPA response. Most of the work on children involves the interrelations between emotion and adrenocortical systems during the first 10-15 min of the stress response. This would include the initial activation of the system and the subsequent emotion and physiological processes involved in continuing or terminating the response. Little attention has been paid to more slowly developing effects of HPA activity on the central nervous system in children, particularly with regard to its influence on children's memories for stressful events and the emotion regulation strategies that they employed during the event. Studies of change or continuity of these interconnections over several exposures to a stressor, as well as between earlier and later points in the activation and regulation process, will be especially important to our understanding of the regulation of affective behavior. PMID- 7984157 TI - Frontal electroencephalographic correlates of individual differences in emotion expression in infants: a brain systems perspective on emotion. AB - Emotion expressions can be characterized by both the type of emotion displayed and the intensity with which the emotion is expressed. Individual differences in these two aspects of emotion appear to vary independently and may perhaps account for distinct dimensions of temperament, personality, and vulnerability to psychopathology. We reviewed several sets of data gathered in our laboratory that indicate that these two dimensions of emotion expression are associated with distinct and independent patterns of frontal EEG activity in infants. Specifically, whereas the type of emotion expression was found to be associated with asymmetries in frontal EEG activity, the intensity of emotion expression was found to be associated with generalized activation of both the right and the left frontal regions. Moreover, we reviewed and provided evidence that measures of asymmetrical frontal activity are better predictors of individual differences in the tendency to express certain emotions, such as distress and sadness, whereas measures of generalized frontal activity are better predictors of individual differences in emotional reactivity and emotion intensity. The neuroanatomical bases of emotion were discussed with special reference to the role of the frontal lobe in emotion regulation. It was hypothesized that the frontal activation asymmetries that have been found to accompany emotion expressions reflect specific regulation strategies. The left frontal region is specialized for regulation strategies involving action schemes that serve to maintain continuity and stability of the organism-environment relation and of ongoing motor schemes, such as those involved in language and the expression of happiness and interest. In contrast, the right frontal region appears to be specialized for regulation strategies that involve processing novel stimuli that disrupt ongoing activity, such as might occur during the expression of fear, disgust, and distress. Furthermore, it was proposed that individual differences in patterns of frontal EEG asymmetries during emotion may be related to socialization influences rather than solely innate factors. It was speculated that the pattern of generalized frontal lobe activation that accompanies the experience of intense emotions may reflect, in part, the relatively diffuse influence of subcortical structures on the cortex and may serve to increase the infant's general readiness to receive and respond to significant external stimuli. PMID- 7984158 TI - Dynamic cerebral processes underlying emotion regulation. PMID- 7984159 TI - Vagal tone and the physiological regulation of emotion. AB - On the basis of current knowledge of neuroanatomy and our previous research with cardiac vagal tone, we have proposed the vagal circuit of emotion regulation. The vagal circuit of emotion regulation incorporates lateral brain function with the regulation of the peripheral autonomic nervous system in the expression of emotion. The vagus and the vagal circuit do not function independently of other neurophysiological and neuroendocrine systems. Research on brain activity (see Dawson, in this volume; Fox, in this volume) and research on adrenocortical activity (see Stansbury & Gunnar, in this volume) demonstrate that EEG and cortisol are related to emotion states and to individual differences similar to those that we have investigated. The vagal circuit emphasizes not only the vagus but also the lateralization of specific brain structures in emotion regulation. The emphasis of the vagal circuit on right-brain-stem structures stimulates several testable hypotheses regarding the function of specific structures in the right brain in emotion regulation. These speculations are consistent with other reports (see Dawson, in this volume; Fox, in this volume) describing asymmetrical EEG activity during expressed emotions. Moreover, the vagal circuit does not exist independently of the brain structures and peptide systems regulating cortisol (see Stansbury & Gunnar, in this volume). Areas in the brain stem regulating vagal activity are also sensitive to the peptides that regulate cortisol (e.g., vasopressin and corticotropin-releasing hormone). In this essay, we have provided information regarding the relation between vagal tone and emotion regulation. A review of research indicates that baseline levels of cardiac vagal tone and vagal tone reactivity abilities are associated with behavioral measures of reactivity, the expression of emotion, and self-regulation skills. Thus, we propose that cardiac vagal tone can serve as an index of emotion regulation. Historically, the vagus and other components of the parasympathetic nervous system have not been incorporated in theories of emotion. Recent developments in methodology have enabled us to define and accurately quantify cardiac vagal tone. Theories relating the parasympathetic nervous system to the expression and regulation of emotion are now being tested in several laboratories. PMID- 7984160 TI - The psychology and psychobiology of relationships. Introduction. PMID- 7984161 TI - Hidden regulators in attachment, separation, and loss. PMID- 7984162 TI - The effects of mother's physical and emotional unavailability on emotion regulation. AB - In summary, emotion dysregulation can develop from brief or more prolonged separations from the mother as well as from the more disturbing effects of her emotional unavailability, such as occurs when she is depressed. Harmonious interaction with the mother or the primary caregiver (attunement) of the mother's physical unavailability were seen in studies of separations from the mother due to her hospitalization or to her conference trips. These separations affected the infants' play behaviors and sleep patterns. Comparisons between hospitalizations and conference trips, however, suggested that the infants' behaviors were more negatively affected by the hospitalizations than the conference trips. This probably related to these being hospitalizations for the birth of another baby- the infants no longer had the special, exclusive relationship with their mothers after the arrival of the new sibling. This finding highlights the critical importance of emotional availability. The mother had returned from the hospital, but, while she was no longer physically unavailable, she was now emotionally unavailable. Emotional unavailability was investigated in an acute form by comparing two laboratory situations, the still face paradigm and the momentary leave taking. The still face had more negative effects on the infants' interaction behaviors than the physical separation. The most extreme form of emotional unavailability, mother's depression, had the most negative effects. The disorganization or emotion dysregulation in this case is more prolonged. Changes in physiology (heart rate, vagal tone, and cortisol levels), in play behavior, affect, activity level, and sleep organization as well as other regulating functions such as eating and toileting, and even in the immune system persist for the duration of the mother's depression. My colleagues and I have suggested that these changes occur because the infant is being chronically deprived of an important external regulator of stimulation (the mother) and thus fails to develop emotion regulation or organized behavioral and physiological rhythms. Finally, individual differences were discussed, including those related to maturity (e.g., prematurity) and temperament/personality (e.g., uninhibited/inhibited or externalizing/internalizing) and those deriving from degree of mother-infant mismatch, such as dissimilar temperaments. Further investigations are needed to determine how long the effects of such early dysregulation endure, how they affect the infant's long-term development, how their effect differs across individuals and across development, and whether they can be modified by early intervention. Eventually, with increasing age, developing skills, and diversity of experience, infants develop individualized regulatory styles. That process, and how it is affected by the mother's physical and emotional unavailability, also requires further investigation. PMID- 7984163 TI - Emotion regulation: influences of attachment relationships. AB - Emotion regulation and quality of attachment are closely linked. It has been proposed here that one influence on individual differences in emotion regulation may be a child's attachment history. Individuals characterized by the flexible ability to accept and integrate both positive and negative emotions are generally securely attached; on the other hand, individuals characterized by either limited or heightened negative affect are more likely to be insecurely attached. While acknowledging the role of infant temperament, I have focused on the role of social factors in examining the link between emotion regulation and attachment. The approach to emotion regulation taken here--that emotion regulation is adaptive in helping a child attain her goals--is esentially a functionalist approach (Bretherton et al., 1986; Campos et al., 1983), consistent with earlier views of emotions as important regulators of interpersonal relationships (Charlesworth, 1982; Izard, 1977). It has been proposed that patterns of emotion regulation serve an important function for the infant: the function of maintaining the relationship with the attachment figure. Emotion regulation has been described as serving this function in two ways. First, the function of maintaining the relationship is thought to be served when infant emotion regulation contributes to the infant's more generalized regulation of the attachment system in response to experiences with the caregiver. Infants who have experienced rejection (insecure/avoidant infants) are thought to minimize negative affect in order to avoid the risk of further rejection. Infants whose mothers have been relatively unavailable or inconsistently available (insecure/ambivalent infants) are thought to maximize negative affect in order to increase the likelihood of gaining the attention of a frequently unavailable caregiver. Both these patterns of emotion regulation help ensure that the child will remain close to the parent and thereby be protected. Second, the function of maintaining the attachment relationship is thought to be served when the infant signals to the parent that she will cooperate in helping maintain the parent's own state of mind in relation to attachment. The minimizing of negative affect of the avoidant infant signals that the infant will not seek caregiving that would interfere with the parent's dismissal of attachment. The heightened negative emotionality of the ambivalent infant signals to the parent that the infant needs her and thus helps maintain a state of mind in which attachment is emphasized. The approach to emotion regulation presented here is congruent with much work examining the socialization of emotions (Lewis & Saarni, 1985; Thompson, 1990). PMID- 7984164 TI - Emotion regulation: a theme in search of definition. AB - Contemporary interest in emotion regulation promises to advance important new views of emotional development as well as offering applications to developmental psychopathology, but these potential contributions are contingent on developmentalists' attention to some basic definitional issues. This essay offers a perspective on these issues by considering how emotion regulation should be defined, the various components of the management of emotion, how emotion regulation strategies fit into the dynamics of social interaction, and how individual differences in emotion regulation should be conceptualized and measured. In the end, it seems clear that emotion regulation is a conceptual rubric for a remarkable range of developmental processes, each of which may have its own catalysts and control processes. Likewise, individual differences in emotion regulation skills likely have multifaceted origins and are also related in complex ways to the person's emotional goals and the immediate demands of the situation. Assessment approaches that focus on the dynamics of emotion are well suited to elucidating these complex developmental and individual differences. In sum, a challenging research agenda awaits those who enter this promising field of study. PMID- 7984165 TI - A functionalist perspective on the nature of emotion. PMID- 7984166 TI - Definitions and concepts of emotion regulation. Introduction. PMID- 7984167 TI - Origins and outcomes of individual differences in emotion regulation. AB - Recent discussions of emotion regulation in infants and young children have focused on the individual differences that exist in this domain of development. Such differences may be seen at the outcome level, in terms of variations in the development of particular strategies as a result of infant or caregiver effects. In this essay, a general hypothetical pathway to emotion regulation and dysregulation comprising interactions among a number of internal and external factors thought to impinge on the emotion regulation process has been proposed. Relations among these factors were hypothesized, and examples of pathways to particular types of social behavior in a peer setting were advanced. It is suggested that empirical confirmation of these pathways would enhance our understanding of adaptive regulatory behavioral patterns as well as patterns that may be dysregulating and potentially place the child at risk for the development of psychopathological disorders. To be successful, such studies must include consideration of the reciprocal interaction between the infant's behavioral and cognitive traits and the caregiving environment over extended periods of early development. PMID- 7984168 TI - On the nature of emotion. AB - This essay has tried to make three points. First, humans are capable of a large number of affect states (the exact number is not yet known), each marked by a distinct profile of physiology, cognition, and behavior, and each requiring a distinct name. Second, a distinction should be made among acute emotions, chronic moods, and temperamental vulnerabilities to a particular emotion state. Finally, research on human affects will profit from a return to, and a reinterpretation of, Freud's suggestion of unconscious affect states. Such inquiry would provide a corrective to the current reliance on the verbal reports of phenomenal states on questionnaires or in interviews as either the only, or the primary, index of an emotion. Continued use of this strategy will limit analyses to a small number of heterogeneous states that happen to have a popular English name and will retard discovery of the larger number of affect states that are of significance for human function. Discovery of these states will require use of new sources of evidence to supplement popular ones, including facial and postural expressions, muscle tension, EEG, vagal tone, heart-rate changes, blood pressure, GSR, facial temperature, and blood or saliva indexes of norepinephrine, opioids, and cortisol. When the cosmologist James Peebles was asked to guess the exact numerical answers to a series of astronomical puzzles, like the age of the universe or of a distant star, he replied, "If someone gave me on a tablet of clay the answer and the numbers, I would be disappointed. I would throw it away because the great discoveries are not going to be a final number, but the method you come to apply to learn that number." PMID- 7984169 TI - The development of emotion regulation and dysregulation: a clinical perspective. AB - Clinical conceptualizations of emotion that stress its disruptive influences and functional models of emotion that emphasize its adaptive aspects can be integrated into a developmental psychopathology framework. Under certain conditions, emotion regulation may develop dysregulatory aspects that can become a characteristic of an individual's coping style. This style may then jeopardize or impair functioning and become associated with symptomatic, disordered functioning. Emotional development provides a critical vantage point from which to study the development of symptomatology and psychopathology, particularly given the prevalence of emotional symptoms in various forms of psychopathology. Dimensions of emotionality that can be used to characterize dysregulation include access to the range of emotions, flexible modulation of intensity, duration, and transitions between emotions, acquisition and use of cultural display rules, and the ability to reflect on the complexity and value of one's own emotions in a self-supporting manner. Developmental psychopathology provides a framework within which to examine how emotions are regulatory, how their regulation changes over time, and under what conditions an adaptive emotion process can develop into a pattern of dysregulation that then becomes, or sustains, some symptoms of mental disorders. Such research requires samples that include children with and without risk or presence of particular mental health problems, paradigms that allow the examination of dimensions of emotionality in context and provide multiple assessments that include observations of children's reactions beyond what they themselves can report, and analyses that extend beyond simple global aggregates such as positive and negative emotion. We believe that it is particularly important to study children and their families in situations that challenge their emotional adaptation. The developmental tasks of emotional life evolve in exchanges between the child and the world of events and relationships. The emotional conditions of early childhood appear to be very important in optimizing or interfering with how the child's emotionality regulates his or her interpersonal and intrapsychic functioning and how the child learns to regulate emotion. The experiences that accrue around emotional events influence the stable aspects of the developing personality and become trait-like aspects of the person (Malatesta & Wilson, 1988). Dysregulation occurs when an emotional reaction loses breadth and flexibility. If a dysregulatory pattern becomes stabilized and part of the emotional repertoire, it is likely that this pattern is a symptom and supports other symptoms. When development and adaptation are compromised, the dysregulation has evolved into a form of psychopathology. The line between normative variations and clinical conditions is not clearly drawn.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 7984170 TI - Molecular characterisation and localisation of an Onchocerca volvulus pi-class glutathione S-transferase. AB - Glutathione S-transferases (GSTs) constitute a major detoxification mechanism in helminth organisms and are regarded vaccine candidates against helminth infections. Onchocerca volvulus glutathione-binding proteins were purified from the aqueous soluble fraction of homogenised adult females by affinity chromatography on glutathione-agarose. The eluted proteins had a specific GST activity of 1.6 mumol min-1 mg-1. Immunohistochemical studies localised these antigens in the hypodermis, the wall of the seminal receptacle and spermatozoa of adult worms. A lambda gt11 clone was isolated from an expression library of O. volvulus by immunoscreening. Sequence analysis revealed that it encoded a pi class GST with 60% identity with Caenorhabditis elegans and up to 45% identity with mammalian pi-class GSTs. Antibodies affinity selected with recombinant GST demonstrated cross-reactivity between Litomosoides sigmodontis and O. volvulus GSTs. PMID- 7984171 TI - Cloning and characterization of a cDNA encoding phosphofructokinase from Schistosoma mansoni. AB - Schistosoma mansoni, a human parasitic worm, depends on anaerobic glycolysis as the main source of energy. Phosphofructokinase (ATP: D-fructose-6-phosphate 1 phosphotransferase, EC 2.7.1.11; PFK) limits the rate of glycolysis in these organisms and it has been found to be a target for some antischistosomal agents. A cDNA clone from this parasite has been isolated and characterized. The cDNA is 3046 base pairs long, contains an open reading frame of 2346 bp and codes for a deduced protein of 781 amino acids. The putative protein encoded by the clone has an exact match with the human muscle PFK of 58% and a 73% match when conserved amino acid substitutions are considered. ATP and Fructose-6-P sites have been identified by crystallographic data in the Escherichia coli and Bacillus stearothermophilus PFKs. There is excellent homology between those PFKs and the schistosome PFK at those sites. The PFK-coding cDNA was expressed in insect cells and was shown to be enzymatically active. Western blot analysis of the recombinant protein in cell extracts gave a positive band with the expected molecular weight of 86 kDa. PMID- 7984172 TI - An amplified DNA element in Leishmania encodes potential integral membrane and nucleotide-binding proteins. AB - LD1 is a 27.5-kb sequence that occurs in an approx. 2.2-Mb chromosome in all species and strains of Leishmania. In Leishmania infantum MHOM/BL/67/ITMAP263, LD1 is also present as an inverted dimeric repeat in multicopy, 55-kb circular molecules. Sequence analysis of a 7873-nt segment derived from the circular DNA reveals 4 open reading frames (ORFs) with potential protein coding function. One ORF predicts a protein with an ATP/GTP binding site motif. Another ORF predicts a protein with 10-12 potential membrane-spanning domains, suggesting that it encodes an integral membrane protein. This protein also has homology with that predicted by the ESAG10 gene of Trypanosoma brucei. PMID- 7984173 TI - Expression and characterization of a rac family protein kinase of Entamoeba histolytica. AB - We previously reported the isolation from Entamoeba histolytica of a novel rac family protein kinase gene, termed Ehrac1, for "related to cAMP-dependent protein kinases and protein kinase Cs". To study the function and properties of this kinase gene further, we fused the full-length coding region and the truncated catalytic domain of the Ehrac1 gene in frame with the gene encoding glutathione S transferase in the pGEX-KG vector and expressed the fusion in Escherichia coli. The thrombin-cleaved and uncleaved fusion proteins, GST-Ehrac1 and GST-Ehrac1-c (catalytic domain), were purified and found to exhibit similar protein kinase activities. The Ehrac1 fusion kinase was found to phosphorylate serine/threonine residues exclusively in vitro. The preferred substrate for the enzyme was histone H1 with a Km of approx. 14 microM. Histone H3 and kemptide were phosphorylated at about half the rate of histone H1. Protamine, enolase, bovine serum albumin, and poly (Glu:Tyr) were not substrates for the enzyme. The protein kinase activity was higher in the presence of Mn2+ than Mg2+. Neither cAMP, Ca2+, nor Ca2+/calmodulin stimulated enzyme activity. The pH optimum of the enzyme was 7.5. The Ehrac1 kinase can utilize GTP as well as ATP as a phosphate donor with an apparent Km of 80 microM. Enzyme activity was inhibited 30-40% by a crude cAMP dependent protein kinase inhibitor from rabbit and by thiol reagents. The expression and purification of enzymatically active Ehrac1 protein kinase should allow further analysis of the regulation and signal transduction pathways of E. histolytica. PMID- 7984174 TI - Changes in Trypanosoma cruzi infectivity by treatments that affect calcium ion levels. AB - The possible role of the intracellular Ca2+ level in the regulation of Trypanosoma cruzi infectivity was explored by measuring the capacity of trypomastigote forms of this organism to invade mammalian host cells after treatments which decrease or elevate cytoplasmic Ca2+. Parasites loaded with either bis-(o-aminophenoxy)-ethane-N,N,N',N' tetraacetic acid (BAPTA) or 2-([2 bis(carboxymethyl)-amino-5-methylphenoxy]methyl)-6-nethoxy-8 - bis(carboxymethyl)aminoquinoline (Quin-2) to chelate Ca2+ displayed significantly decreased infectivity. This effect was denoted by reductions in both the proportion of rat heart myoblasts invaded by the parasite in vitro and the number of trypanosomes penetrating these host cells, the extents of which were BAPTA or Quin-2 concentration dependent. Consistent with these observations, inhibitory effects were also recorded when the parasite was pretreated with the calmodulin binding phenothiazines trifluoperazine and chlorpromazine or with felodipine, a chemically different type of calmodulin antagonist, for as little as 5 min. In contrast, pretreatment with the Ca2+ ionophore ionomycin, which elevated Ca2+ levels in T. cruzi, significantly enhanced the infective capacity of the parasite. These results point to the existence of a Ca(2+)-dependent mechanism that regulates the invasive capacity of T. cruzi. PMID- 7984175 TI - Analysis of a single-domain P-glycoprotein-like gene in the early-diverging protist Trichomonas vaginalis. AB - We have characterized a gene encoding an Adenosine triphosphate (ATP) Binding Cassette (ABC) transmembrane protein from Trichomonas vaginalis, an early diverging protozoan parasite. This gene, Tvpgp1, encodes a 589-amino acid protein with an amino-terminal hydrophobic region, 6 potential membrane-spanning segments and a carboxy-terminal ATP binding site. Tvpgp1 is most similar in sequence to mammalian P-glycoproteins, 170 kDa transport proteins which are frequently overexpressed in multiple drug-resistant (Mdr) tumor cell lines. However, Tvpgp1 is half the size of typical P-glycoproteins which are tandem duplications. These data suggest that the duplication/fusion events which gave rise to the bipartite structure comprised of 2 similar halves which characterize eukaryotic P glycoproteins may have occurred after the divergence of trichomonads (Parabasalia) from the main line of eukaryotic evolutionary descent. We have examined 7 metronidazole resistant strains of T. vaginalis to determine whether the Tvpgp1 gene is overexpressed or amplified. 2 drug resistant strains show a 2 3-fold overexpression and one shows a 20-fold overexpression of Tvpgp mRNA. The gene is not amplified in any of the drug resistant strains. On the contrary, 4 of the 7 resistant strains lack one of 2 Tvpgp genes found in drug-sensitive strains. PMID- 7984176 TI - Characterization of a DNA-binding factor that recognizes the 22-base pair trans spliced leader sequence in Ascaris lumbricoides. PMID- 7984177 TI - Ascorbate variations and dehydroascorbate reductase activity in Trypanosoma cruzi epimastigotes and trypomastigotes. PMID- 7984178 TI - Genes for histone H3 in Trypanosoma cruzi. PMID- 7984179 TI - An episome of Trypanosoma brucei can exist as an extrachromosomal element in a broad range of trypanosomatids but shows different requirements for stable replication. PMID- 7984180 TI - N-terminal amino acid sequence of the Plasmodium falciparum merozoite surface protein-1 polypeptides. PMID- 7984181 TI - Atomic absorption spectrophotometric measurement of intracellular arsenite in arsenite-resistant Leishmania. PMID- 7984182 TI - Primary structure of the Entamoeba histolytica gene (Ehvma1) encoding the catalytic peptide of a putative vacuolar membrane proton-transporting ATPase (V ATPase). PMID- 7984183 TI - Phylogenetic heterogeneity of three Crithidia spp. vs. Crithidia fasciculata. PMID- 7984184 TI - Host specificity of ribosomal DNA variation in sylvatic Trypanosoma cruzi from North America. PMID- 7984185 TI - An intron-containing gene coding for a novel 39-kilodalton antigen of Entamoeba histolytica. PMID- 7984186 TI - Mapping the genetic locus implicated in cytoadherence of Plasmodium falciparum to melanoma cells. AB - Many lines of Plasmodium falciparum undergo a deletion of the right end of chromosome 9 during in vitro cultivation accompanied by loss of cytoadherence to melanoma cells. The deletion also results in loss of expression of PfEMP1, the putative cytoadherence ligand, suggesting that PfEMP1 or a regulatory gene controlling PfEMP1 expression is encoded in this region. Initially a library of short fragments highly enriched for the right arm of chromosome 9 was constructed in bacteriophage lambda. Clones from this library were obtained randomly by the polymerase chain reaction (PCR) technique, sequenced and used to screen a yeast artificial chromosome (YAC)-P. falciparum library by PCR so that the region could be cloned and physically mapped in detail. We have used probes from this region to demonstrate that clones derived from ITG2 have undergone a deletion of intermediate length on chromosome 9. This could explain the unusual stability of cytoadherence in these clones. PMID- 7984187 TI - Sequence diversity of the erythrocyte membrane antigen 1 in various strains of Plasmodium chabaudi. AB - We have determined the complete genomic sequence of the Plasmodium chabaudi erythrocyte membrane antigen (PcEMA1) in 4 different parasite strains. The gene structure consisted of a short region encoding a signal sequence separated from the main coding region by an intervening sequence. The overall identity of the three P. chabaudi adami deduced protein sequences to their consensus was 100%, 99.8% and 88% for 556KA, DK and DS respectively, with a general pattern of increasing divergence from the N- to the C-terminus. The P. chabaudi chabaudi strain CB was 72% homologous to the P. chabaudi adami consensus sequence. A gene related to PcEMA1, designated PcEMA1-R, has been identified in the genome of P. chabaudi adami but not in P. chabaudi chabaudi. The partial sequence for this gene in P. chabaudi adami strain DS predicts that it could encode a truncated form of PcEMA1, but its status as a pseudogene or an independent, expressed gene has not been resolved. PMID- 7984188 TI - The Plasmodium falciparum protein RESA interacts with the erythrocyte cytoskeleton and modifies erythrocyte thermal stability. AB - The ring-infected erythrocyte surface antigen (RESA) associates with spectrin in the erythrocyte membrane (Foley, M., Tilley, L., Sawyer, W. H. and Anders, R. F. (1991) Mol. Biochem. Parasitol., 46, 137-148). A fragment of the RESA protein, which was expressed in Escherichia coli, was found to bind to inside-out vesicles of erythrocyte membranes in an apparently saturable manner. Upon extraction of inside-out vesicles with Triton X-100, the RESA fragment remained associated with the erythrocyte cytoskeleton. Using the technique of steady-state fluorescence polarisation, we have studied the thermal denaturation of fluorescein-labelled spectrin in the presence of recombinant RESA. We found that the RESA fragment partially protected spectrin against heat-induced conformational changes. Furthermore, erythrocytes infected with a RESA (-) laboratory strain (FCR3) were shown to be more susceptible to heat-induced fragmentation than erythrocytes infected with a RESA (+) strain of the parasite. RESA does not, however, appear to play an essential role in the invasion process per se as erythrocytes resealed to contain anti-RESA antibodies were efficiently invaded. PMID- 7984189 TI - Karyotype analysis of the monogenetic trypanosomatid Leptomonas collosoma. AB - In order to develop a genetic system for the monogenetic trypanosomatids, we have analyzed the molecular karyotype of Leptomonas collosoma based on chromosome separation by clamped homogeneous electric field (CHEF) gel electrophoresis. The chromosome location of 5 RNA coding genes (SL, U6, 5S, 7SL and rRNA) and 2 protein coding genes (for HSP83 and alpha-tubulin) was determined. All of the L. collosoma genes examined were found on at least 2 chromosomes, which differ in size in the range of 100-500 kb, suggesting that the organism is diploid. The weighted sum of L. collosoma chromosomes separated by CHEF analysis was approximately 62 +/- 3 Mb, whereas the genome size determined by FACS was estimated at approx. 80 Mb. This suggests that some of the homologous chromosomes differ in their size. The analysis presented here may facilitate studies on the function of individual genes, and on the genetic stability of this organism. PMID- 7984190 TI - Characterization of trafficking pathways and membrane genesis in malaria-infected erythrocytes. AB - The origin of membraneous structures in the cytoplasm of human erythrocytes infected with the malaria parasite, Plasmodium falciparum, was determined by confocal fluorescence imaging microscopy. When infectious merozoites invaded erythrocytes labeled with the fluorescent, lipophilic, non-exchangeable molecules DiIC16 or DiOC16, a ring of fluorescence was observed surrounding the internal parasite, indicating that the parasitophorous vacuolar membrane (PVM) is formed in part from the erythrocyte membrane. As the parasites matured, fluorescent vesicles were seen to be exported into the erythrocyte cytoplasm, beginning at 6 h post-invasion. During intraerythrocytic development, these dyes were transferred from the PVM to the parasite. When fluorescently labeled merozoites were released from these cells and invaded unlabeled erythrocytes, fluorescence was confined to the parasite throughout the entire erythrocytic cycle. Taken together, these results demonstrate that all vesicles/membranous compartments in the erythrocyte cytoplasm of parasitized erythrocytes (IRBC) contain membrane derived from the PVM. Based on this information, we define pathways that the parasite utilizes to export proteins and lipids to the host cell cytoplasm and surface membrane. When IRBC were labeled post-invasion with DiIC16 or DiOC16 and the parasites allowed to mature for one life cycle, the dyes were confined to the erythrocyte membrane, demonstrating that the host cell membrane of IRBC does not endocytose and there is no membrane exchange from the erythrocyte to the parasite. This investigation helps to resolve two long-standing controversies and provides new insights into the transport pathways that malaria parasites utilize during their development within host erythrocytes. PMID- 7984191 TI - Analysis of expressed sequence tags from Plasmodium falciparum. AB - An initiative was undertaken to sequence all genes of the human malaria parasite Plasmodium falciparum in an effort to gain a better understanding at the molecular level of the parasite that inflicts much suffering in the developing world. 550 random complimentary DNA clones were partially sequenced from the intraerythrocytic form of the parasite as one of the approaches to analyze the transcribed sequences of its genome. The sequences, after editing, generated 389 expressed sequence tag sites and over 105 kb of DNA sequences. About 32% of these clones showed significant homology with other genes in the database. These clones represent 340 new Plasmodium falciparum expressed sequence tags. PMID- 7984192 TI - Transluminal placement of endovascular stent-grafts for the treatment of descending thoracic aortic aneurysms. AB - BACKGROUND: The usual treatment for thoracic aortic aneurysms is surgical replacement with a prosthetic graft, but the associated morbidity and mortality are considerable. We studied the use of transluminally placed endovascular stent graft devices as an alternative to surgical repair. METHODS: We evaluated the feasibility, safety, and effectiveness of transluminally placed stent-graft to treat descending thoracic aortic aneurysms in 13 patients over a 24-month period. Atherosclerotic, anastomotic, and post-traumatic true or false aneurysms and aortic dissections were treated. The mean diameter of the aneurysms was 6.1 cm (range, 5 to 8). The endovascular stent-grafts were custom-designed for each patient and were constructed of self-expanding stainless-steel stents covered with woven Dacron grafts. RESULTS: Endovascular placement of the stent-graft prosthesis was successful in all patients. There was complete thrombosis of the thoracic aortic aneurysm surrounding the stent-graft in 12 patients, and partial thrombosis in 1. Two patients initially had small, residual patent proximal tracts into the aneurysm sac, but both tracts thrombosed within two months after the procedure. In four patients, two prostheses were required to bridge the aneurysm adequately. There have been no deaths or instances of paraplegia, stroke, distal embolization, or infection during an average follow-up of 11.6 months. One patient with an extensive chronic aortic dissection required open surgical graft replacement four months later because of progressive dilatation of the arch. CONCLUSIONS: These preliminary results demonstrate that endovascular stent-graft repair is safe in highly selected patients with descending thoracic aortic aneurysms. This new method of treatment will, however, require careful long-term evaluation. PMID- 7984193 TI - Complications and failures of subclavian-vein catheterization. AB - BACKGROUND: Although catheterization of the subclavian vein is a common procedure, the risk factors for complications and failures, with the exception of the physician's experience, are poorly understood. Ultrasonography has been recommended to help guide the placement of central venous catheters. METHODS: We conducted a prospective randomized trial of ultrasound-guided location of the subclavian vein as compared with standard insertion procedures. In the group of patients undergoing catheterization with ultrasound guidance, the site of the insertion was marked before the catheterization attempt; real-time ultrasound guidance was not used. The 821 eligible patients (411 in the ultrasound group and 410 in the control group) underwent catheterization in a single procedure suite under controlled nonemergency conditions, in most cases for the administration of chemotherapy. RESULTS: Ultrasound guidance had no effect on the rate of complications or failures of subclavian-vein catheterization (risk ratio for complications, 1.00; 95 percent confidence interval, 0.66 to 1.52; risk ratio for failures, 1.04; 95 percent confidence interval, 0.72 to 1.50). In multivariate analyses, prior major surgery in the region (P = 0.002), a body-mass index (the weight in kilograms divided by the square of the height in meters) higher than 30 or lower than 20 (P = 0.009), and previous catheterization (P = 0.043) were associated with failed attempts. Complications were also associated with failed attempts: 52 of the 721 patients (7.2 percent) in whom catheterization was successful had complications, as compared with 28 of the 100 patients (28 percent) in whom physicians were unable to place catheters. The number of needle passes was strongly associated with the rates of failure and complications. The complication rate rose from 4.3 percent with one pass to 24.0 percent with more than two passes. CONCLUSIONS: Ultrasound guidance of subclavian-vein catheterization, as used in this study, was not beneficial. In patients at highest risk for complications and failures, catheterization should be attempted by the most experienced physicians available. PMID- 7984194 TI - Timing of vulnerability of the brain to iodine deficiency in endemic cretinism. AB - BACKGROUND: Endemic cretinism, caused by severe iodine deficiency during pregnancy, is the world's most common preventable cause of mental retardation. It can be prevented by iodine treatment before conception, but whether it can be prevented or ameliorated by treatment during pregnancy or after delivery is not known. METHODS: In a severely iodine-deficient area of the Xinjiang region of China, we systematically administered iodine to groups of children from birth to three years of age (n = 689) and women at each trimester of pregnancy (n = 295); we then followed the treated children and the babies born to the treated women for two years. We used three independent measures of neural development: the results of the neurologic examination, the head circumference (which correlates with brain weight in the first postnatal year), and indexes of cognitive and motor development. Untreated children one to three years of age, who were studied when first seen, served as control subjects. RESULTS: The prevalence of moderate or severe neurologic abnormalities among the 120 infants whose mothers received iodine in the first or second trimester was 2 percent, as compared with 9 percent among the 752 infants who received iodine during the third trimester (through the treatment of their mothers) or after birth (P = 0.008). The prevalence of microcephaly (defined as a head circumference more than 3 SD below U.S. norms) decreased from 27 percent in the untreated children to 11 percent in the treated children (P = 0.006), and the mean (+/- SD) developmental quotient at two years of age increased (90 +/- 14, vs. 75 +/- 18 in the untreated children; P < 0.001). Treatment in the third trimester of pregnancy or after delivery did not improve neurologic status, but head growth and developmental quotients improved slightly. Treatment during the first trimester, which was technically problematic, improved the neurologic outcome. CONCLUSIONS: Up to the end of the second trimester, iodine treatment protects the fetal brain from the effects of iodine deficiency. Treatment later in pregnancy or after delivery may improve brain growth and developmental achievement slightly, but it does not improve neurologic status. PMID- 7984195 TI - Treatment of nevus of Ota with the Q-switched ruby laser. AB - BACKGROUND: Nevus of Ota is a benign bluish or gray-brown lesion of the eye and the surrounding skin that has been reported to occur in about 1 in 200 people in Japan. Prior treatments have either been ineffective or caused scarring. The Q switched ruby laser can produce very short high-energy pulses and can selectively target cells that contain pigment, such as dermal melanocytes. METHODS: We treated the skin lesions of 114 patients (25 male and 89 female) with nevi of Ota with a Q-switched ruby laser set to deliver pulses of 6 J per square centimeter of body-surface area at a wavelength of 694.3 nm, with a pulse duration of 30 nanoseconds. The interval between treatments ranged from three to four months. Five dermatologists who were not familiar with the patients independently compared a full set of pretreatment and post-treatment photographs of each patient and determined the percentage of pigment lightening of the affected areas using standard criteria. RESULTS: Of the 35 patients who received four or five treatments, 33 had an excellent response (lightening of 70 percent or more), and 2 had a good response (lightening of 40 to 69 percent). Of the 31 patients who received three treatments, 4 had an excellent response, 26 a good response, and 1 a fair response (lightening of 10 to 39 percent). Of the 25 patients who received two treatments, 2 had an excellent response, 16 a good response, and 7 a fair response. Of the 23 patients who received one treatment, 3 had a good response, 13 a fair response, and 7 no response (lightening of 9 percent or less). No patient had hypertrophic or atrophic scarring; eight patients had postinflammatory hyperpigmentation for up to two months after the first treatment. CONCLUSIONS: Selective photothermolysis with the Q-switched ruby laser is a safe and effective method for lightening nevi of Ota. Multiple treatments increase the response rate. PMID- 7984196 TI - Images in clinical medicine. Transfemoral repair of abdominal aortic aneurysm. PMID- 7984197 TI - Habitually wandering patients. AB - BACKGROUND: Physicians are sometimes confronted with patients who gain admission to one hospital after another, sometimes referred to as "wandering patients." Little is known about the presenting symptoms of these patients, their use of hospital resources, or the costs of their medical care. We analyzed the demographic and clinical characteristics of wandering patients served by Department of Veterans Affairs medical centers (VAMCs). METHODS: For each patient they admit, all 159 hospitals in the Veterans Affairs medical system submit demographic and diagnostic information to a central data base at the Data Processing Center in Austin, Texas. We searched these records to identify patients who were admitted to four or more VAMCs within each year from fiscal year 1988 through 1992. Patients so identified in any one year were called "wanderers"; those identified in all five years were designated "habitual wanderers." RESULTS: We identified 1013 wanderers in 1988. The number gradually declined each year to 729 in 1993. In 1991 there were 810 wandering patients, who averaged about eight admissions per year and over 100 days of inpatient care; they accounted for about $26.5 million in costs for inpatient and outpatient care in that year. Only 35 patients wandered in all five years from 1988 through 1992. The most common discharge diagnoses of these 35 men were related to substance abuse (mostly alcoholism) and mental disorders. Their 2268 admissions and 7832 outpatient visits cost an estimated $6.5 million over the five-year period. CONCLUSIONS: Patients who are repeatedly admitted to different hospitals- wandering patients--accumulate high numbers of admissions, cause diagnostic confusion, and receive uncoordinated care. Because of the complexity of their disorders, such patients require case management on a regional or national basis. PMID- 7984198 TI - Accidental hypothermia. PMID- 7984199 TI - Case records of the Massachusetts General Hospital. Weekly clinicopathological exercises. Case 46-1994. A 35-year-old smoker with an air-fluid level in an upper lobe bulla. PMID- 7984200 TI - Iodine deficiency and fetal brain damage. PMID- 7984202 TI - The care of injection-drug users with HIV infection. PMID- 7984201 TI - Veterans who return to hospitals again and again. PMID- 7984203 TI - The care of injection-drug users with HIV infection. PMID- 7984204 TI - Management of infections caused by antibiotic-resistant Streptococcus pneumoniae. PMID- 7984205 TI - Insect stings. PMID- 7984206 TI - Management of infections caused by antibiotic-resistant Streptococcus pneumoniae. PMID- 7984207 TI - Case 30-1994: antiendomysial antibodies and celiac disease. PMID- 7984208 TI - Organic osmolytes in the brain of an infant with hypernatremia. PMID- 7984209 TI - Efficacy and safety of cyclosporine in renal-transplant recipients. PMID- 7984210 TI - Efficacy and safety of cyclosporine in renal-transplant recipients. PMID- 7984211 TI - Metabolic mimicry--renal failure with normal renal function. PMID- 7984212 TI - Iturin A: a potential new fungicide for stored grains. AB - The removal of many synthetic fungicides from the market has created a demand for new, environmentally safe fungicides. Iturin A, a cyclic lipopeptide produced by Bacillus subtilis, has strong antifungal properties and low mammalian toxicity. To determine the efficacy of this compound as a potential fungicide on stored feed grains, lots of corn, peanuts and cottonseed were treated with varying concentrations of iturin A. The mycoflora of treated seed was assayed along with that of untreated seed and seed treated with fungicides used commercially for planting seed. Fungal species varied considerably in their sensitivity to iturin A. Significant reductions in total mycoflora occurred in most seed lots tested at iturin A concentrations of 50 to 100 ppm. PMID- 7984213 TI - Curvularia lunata peritonitis complicating peritoneal dialysis. AB - A case of peritonitis due to Curvularia lunata during continuous ambulatory peritoneal dialysis is reported. Diagnosis was established by culture of dialysis effluent and peritoneal exudate, and was also confirmed through histological examination. PMID- 7984214 TI - Alkaline phosphatase at the cell wall of the yeast phase of Paracoccidioides brasiliensis. AB - The activity of alkaline phosphatase demonstrated by histochemical techniques was shown at the cell wall of the yeast form of Paracoccidioides brasiliensis at 3, 6, and 9 days of culture. The results showed a very active deposition at the cell wall as early as 9 days of culture of the fungus which made us think an inactive salt precipitate was also present. PMID- 7984215 TI - Report of chronic subcutaneous abscesses caused by Exophiala spinifera. AB - A case of phaeohyphomycosis with subcutaneous abscesses involving skin, muscle and bone was caused by Exophiala spinifera. This is the first report of E. spinifera causing bone degeneration in Recife-PE, Brazil. PMID- 7984216 TI - Survey of mycotic and bacterial keratitis in Sri Lanka. AB - Over a two-year period (1976-1977 and 1980-1981), 66 cases of bacterial and mycotic cases of keratitis were diagnosed in the Eye Clinic of the General Hospital in Kandy, Sri Lanka. The clinical and microbiologic aspects of these cases are described. Noteworthy was the first known human case caused by Paecilomyces farinosus, a geophilic species, commonly encountered as an insect parasite throughout the world. The bacterial and the other fungal etiologic agents isolated and identified were: Pseudomonas aeruginosa, Streptococcus pneumoniae, Aspergillus flavus, A. niger, Fusarium oxysporum, and Lasiodiplodia theobromae. In vitro the fungi showed sensitivity in decreasing order to flucytosine, nystatin, amphotericin B and econazole. Due to the out-patient status of the patients, their in-vivo response to treatment was not assessable. PMID- 7984217 TI - Class-specific antibody in human dermatophytosis reactive with Trichophyton rubrum derived antigen. AB - Dermatophyte infections induce a humoral immune response and an enzyme linked immunosorbent assay was used to detect specific antibody classes against antigen derived from Trichophyton rubrum. Sera from 19 acute patients, 18 chronic patients, and 27 normal controls were evaluated. Mean IgG titers against dermatophyte antigen were significantly higher in all patients than in controls. Mean IgM levels were significantly higher in acute patients than in controls. No significant difference was detected in IgE titers between the patients and controls. These results do not reveal whether the humoral immune response has a role in the progression of the infection. PMID- 7984218 TI - Systematic evaluation of the adrenocortical function in patients with paracoccidioidomycosis. AB - Limited cortisol response to ACTH stimulation has been documented in 22 to 48% of patients with paracoccidioidomycosis (PM). Different approaches to interpret the test and inadequate selection of patients preclude an accurate appraisal of the actual incidence of adrenal insufficiency in PM. Rapid cosyntropin (ACTH) stimulation tests were performed in 38 consecutive patients (9 with the localized and 29 with the disseminated form of PM) and 40 normal controls. Subnormal cortisol responses to ACTH (60 minutes post-ACTH values below 455 nmol/l, 95% confidence limits) were found in only 4 patients (14%) with disseminated PM. If a retrospective sample of 6 patients studied previously (in whom tests were indicated due to clinical suspicion of Addison's disease) were included, or if the absolute cortisol increment above baseline was used for interpretation, we would find figures closer to those previously reported (23 and 24%, respectively). These data reflect that non-systematic evaluation or selection of a substandard criterion to interpret the test overestimates the frequency of adrenocortical insufficiency in PM. PMID- 7984220 TI - Pitfalls of co-authorship. PMID- 7984219 TI - Isolation and characterization of new chlamydosporol related metabolites of Fusarium chlamydosporum and Fusarium tricinctum. AB - Fusarium chlamydosporum strain T-826 isolated from corn in the USA produced chlamydosporol and two analogs which have been identified by various spectroscopic techniques as: 7,8-dihydro-5-hydroxy-4-methoxy-trans-7,8-dimethyl 2H,5H-pyrano(4, 3-b)pyran-2-one (or isochlamydosporol) and 4-methoxy-5 hydroxymethyl-6-(3-butan-2-ol)-2H-pyran-2-one (or chlamydospordiol). Chlamydosporol (compound a + b) chlamydospordiol (compound c) and isochlamydosporol (compound d) were produced together (up to 6000 micrograms/g) by 3 out of 11 isolates of F. chlamydosporum and by 3 out of 24 isolates of F. tricinctum from various substrates and geographic origin. Three isolates of F. chlamydosporum and one isolate of F. tricinctum produced only chlamydospordiol and 2 isolates of F. tricinctum produced chlamydosporol (a + b), and chlamydospordiol (c). PMID- 7984222 TI - UK 'protects' health research funds. PMID- 7984221 TI - ORI finds Imanishi-Kari guilty of misconduct, proposes 10-year ban. PMID- 7984223 TI - Italian drug firms rethink ban on conference support. PMID- 7984224 TI - Patents stalemate on biotechnology. PMID- 7984225 TI - Court asked to halt inquiry into psychologist's suicide. PMID- 7984226 TI - Salk Institute president is replaced. PMID- 7984227 TI - France plans national gene therapy strategy. PMID- 7984228 TI - UK 'should abandon quarantine law'. PMID- 7984229 TI - Forensic DNA typing dispute. PMID- 7984230 TI - Genetics. In search of a satiety factor. PMID- 7984231 TI - Developmental biology. Insects take a homeotic test. PMID- 7984232 TI - Protein-protein interaction. Complex flexibility. PMID- 7984233 TI - DNA damage and melanogenesis. PMID- 7984234 TI - SNARE motif and neurotoxins. PMID- 7984235 TI - Visual reference. PMID- 7984236 TI - Positional cloning of the mouse obese gene and its human homologue. AB - The mechanisms that balance food intake and energy expenditure determine who will be obese and who will be lean. One of the molecules that regulates energy balance in the mouse is the obese (ob) gene. Mutation of ob results in profound obesity and type II diabetes as part of a syndrome that resembles morbid obesity in humans. The ob gene product may function as part of a signalling pathway from adipose tissue that acts to regulate the size of the body fat depot. PMID- 7984237 TI - Crystal structure at 1.92 A resolution of the RNA-binding domain of the U1A spliceosomal protein complexed with an RNA hairpin. AB - The crystal structure of the RNA-binding domain of the small nuclear ribonucleoprotein U1A bound to a 21-nucleotide RNA hairpin has been determined at 1.92 A resolution. The ten-nucleotide RNA loop binds to the surface of the beta sheet as an open structure, and the AUUGCAC sequence of the loop interacts extensively with the conserved RNP1 and RNP2 motifs and the C-terminal extension of the RNP domain. These interactions include stacking of RNA bases with aromatic side chains of proteins and many direct and water-mediated hydrogen bonds. The structure reveals the stereochemical basis for sequence-specific RNA recognition by the RNP domain. PMID- 7984238 TI - Anaerobic oxidation of hydrocarbons in crude oil by new types of sulphate reducing bacteria. AB - Many crude oil constituents are biodegradable in the presence of oxygen; however, a substantial anaerobic degradation has never been demonstrated. An unusually low content of n-alkanes in oils of certain deposits is commonly attributed to selective utilization of these hydrocarbons by aerobic microorganisms. On the other hand, oil wells and production fluids were shown to harbour anaerobic sulphate-reducing bacteria, but their actual electron donors and carbon sources were unknown. On the basis of nutritional properties of various bacterial isolates it was assumed that fatty acids and H2 are potential electron donors for sulphate reduction in situ. Here we demonstrate that hydrocarbons in crude oil are used directly by sulphate-reducing bacteria growing under strictly anoxic conditions. A moderately thermophilic pure culture selectively utilizes n-alkanes in oil for sulphate reduction to sulphide. In addition, a mesophilic sulphate reducing enrichment culture is shown to oxidize alkylbenzenes in oil. Thus, sulphate-reducing bacteria utilizing aliphatic and aromatic hydrocarbons as electron donors may present a significant source of sulphide in oil deposits and oil production plants. PMID- 7984239 TI - Distinct pathways for autocrine and paracrine Wingless signalling in Drosophila embryos. AB - Two secreted proteins, Wingless and Hedgehog, instruct cell fates within the segmented epidermis of Drosophila embryos (reviewed in ref. 5). Wingless (Wg) is expressed by the most posterior cells in each parasegment; Hedgehog (Hh) is expressed in the most anterior cells of the next parasegment. Immediately after gastrulation, the two cell types are mutually dependent. Local Wg signalling stabilizes Hh expression and local Hh signalling stabilizes Wg expression. Direct Wg autoregulation (autocrine signalling) is masked by its paracrine role in maintaining hh, which in turn maintains wg. I have used zeste-white3 (zw3) and patched (ptc) mutant backgrounds to uncouple genetically this positive-feedback loop and to study autocrine Wg signalling. I report here that direct Wg autoregulation differs from Wg signalling to adjacent cells in the importance of fused (fu), smoothened (smo) and cubitus interruptus (ci) relative to zw3 and armadillo (arm). I also find that Wg autoregulation during this early hh dependent phase differs from later Wg autoregulation by lack of gooseberry (gsb) participation. PMID- 7984240 TI - Regulation of embryonic growth and lysosomal targeting by the imprinted Igf2/Mpr gene. AB - The receptor for insulin-like growth factor type 2, also known as the cation independent mannose-6-phosphate receptor (Igf2/Mpr), is a multifunctional receptor thought to play a role in lysosomal targeting, cell growth and signal transduction. Igf2/Mpr has been mapped to the mouse Tme locus and shown to be an imprinted gene, which further suggests a role in embryonic growth regulation. To define the functions of Igf2/Mpr, we have generated mice lacking this gene. We report here that maternal inheritance of an Igf2/Mpr null allele (-/+) as well as homozygosity for the inactive allele (-/-) is generally lethal at birth and mutants are about 30% larger, indicating that maternal expression of Igf2/Mpr is essential for late embryonic development and growth regulation. The phenotype is probably caused by an excess of Igf2 because the introduction of an Igf2 null allele rescued the Igf2/Mpr mutant mice. Mutant mice also have organ and skeletal abnormalities and missort mannose-6-phosphate-tagged proteins. A few (-/+) mice reactivated their paternal Igf2/Mpr allele in some tissues and survived to adults. But no (-/-) mice survived, indicating a role for the reactivated paternal allele in postnatal survival. PMID- 7984241 TI - A topoisomerase II-dependent G2 cycle checkpoint in mammalian cells/. AB - The enzyme DNA topoisomerase II, which removes the catenations formed between the DNA molecules of sister chromatids during replication and is a structural component of chromosome cores, is needed for chromosome condensation in yeast and in Xenopus extracts. Inhibitors of topoisomerase II arrest mammalian cells before mitosis in the G2 phase of the cell cycle, but also produce DNA damage, which causes arrest through established checkpoint controls. It is open to question whether cells need topoisomerase II to leave G2, or control late-cycle progression in response to its activity. Bisdioxopiperazines are topoisomerase II inhibitors that act without producing direct DNA damage; the most potent, ICRF 193, blocks mammalian entry into but not exit from mitosis. Here we show that checkpoint-evading agents such as caffeine override this block to produce abortively condensed chromosomes, indicating that topoisomerase II is needed for complete condensation. We find that exit from G2 is regulated by a catenation sensitive checkpoint mechanism which is distinct from the G2-damage checkpoint. PMID- 7984242 TI - A polyadenylation factor subunit is the human homologue of the Drosophila suppressor of forked protein. AB - Polyadenylation of messenger RNA precursors is a complex process that requires multiple protein factors (for reviews, see refs 1, 2). Cleavage stimulation factor (CstF) is one of these, functioning together with cleavage-polyadenylation specificity factor, two cleavage factors, and poly(A)+ polymerase. CstF is composed of three subunits of M(r) 77, 64 and 50K. The 64K and 50K subunits contain, respectively, an RNP-type RNA-binding domain that contacts the pre-mRNA and transducin repeats characteristic of G-protein beta-subunits. Here we report the cloning and characterization of the 77K subunit of human CstF (referred to as 77K). We show that the 77K subunit is required for formation of active CstF and bridges the 64K and 50K subunits. Sequence analyses indicate that the 77K subunit is the homologue of the protein encoded by the Drosophila melanogaster suppressor of forked (su(f)) gene. Mutations in su(f) can enhance or suppress the effects of transposable element insertions, and our data indicate that this is due to changes in polyadenylation. Both the 77K subunit and the su(f) protein share homology with Saccharomyces cerevisiae RNA14, previously shown to be involved in mRNA metabolism. Our results thus also indicate that components of the complex polyadenylation machinery are conserved from yeast to man. PMID- 7984243 TI - Protein disaggregation mediated by heat-shock protein Hsp104. AB - The heat-inducible members of the Hsp100 (or Clp) family of proteins share a common function in helping organisms to survive extreme stress, but the basic mechanism through which these proteins function is not understood. Hsp104 protects cells against a variety of stresses, under many physiological conditions, and its function has been evolutionarily conserved, at least from Saccharomyces cerevisiae to Arabidopsis thaliana. Homology with the Escherichia coli ClpA protein suggests that Hsp104 may provide stress tolerance by helping to rid the cell of heat-denatured proteins through proteolysis. But genetic analysis indicates that Hsp104 may function like Hsp70 as a molecular chaperone. Here we investigate the role of Hsp104 in vivo using a temperature-sensitive Vibrio harveyi luciferase-fusion protein as a test substrate. We find that Hsp104 does not protect luciferase from thermal denaturation, nor does it promote proteolysis of luciferase. Rather, Hsp104 functions in a manner not previously described for other heat-shock proteins: it mediates the resolubilization of heat-inactivated luciferase from insoluble aggregates. PMID- 7984244 TI - The X-ray structure of a growth hormone-prolactin receptor complex. AB - The human pituitary hormones, growth hormone (hGH) and prolactin (hPRL), regulate a large variety of physiological processes, among which are growth and differentiation of muscle, bone and cartilage cells, and lactation. These activities are initiated by hormone-receptor binding. The hGH and hPRL receptors (hGHR and hPRLR, respectively) are single-pass transmembrane receptors from class 1 of the haematopoietic receptor superfamily. This classification is based on sequence similarity in their extracellular domains, notably a highly conserved pentapeptide, the so-called 'WSXWS box', the function of which is controversial. All ligands in class 1 activate their respective receptors by clustering mechanisms. In the case of hGH, activation involves receptor homodimerization in a sequential process: the active ternary complex containing one ligand and two receptor molecules is formed by association of a receptor molecule to an intermediate 1:1 complex. hPRL does not bind to the hGH receptor, but hGH binds to both the hGHR and hPRLR, and mutagenesis studies have shown that the receptor binding sites on hGH overlap. We present here the crystal structure of the 1:1 complex of hGH bound to the extracellular domain of the hPRLR. Comparisons with the hGH-hGHR complex reveal how hGH can bind to the two distinctly different receptor binding surfaces. PMID- 7984245 TI - Forewarned is four-armed. AB - A new solution structure of the oligomerization domain of p53 provides a framework for interpreting a wealth of biochemical data but casts doubt on details of an earlier structure. PMID- 7984246 TI - [The pitfalls of the clearance concept in hemodialysis]. AB - The "clearance concept" is rigorously defined by the physicists and bioengineers. However its extension in clinical routine of dialysis therapy is not easy, but essential also to understand the rationale on which is based the currently widely used Kt/V index. The purpose of this paper is to describe the difficulties and pitfalls encountered in measuring the clearance of a substance either provided by a dialyzer or observed in a dialyzed patient. Ambiguities in the definition of clearance may account for sometimes moot estimations of the Kt/V index. PMID- 7984247 TI - [Epidemiology and prognosis of acute renal insufficiency]. AB - The annual incidence of acute renal failure (ARF) in the general population seems close to 150 per million inhabitants. For the past 20 years, there has been an increase in ARF of medical origin and a simultaneous decrease in surgical, traumatic and obstetrical ARF. Drug-induced ARF accounts for 20% of total cases. Factors of poor prognosis include a poor previous health status, the presence of oliguria, cardiac or respiratory insufficiency, sepsis, coma, a need for mechanical ventilation and, most importantly, the number of failing organs. The three main severity scoring systems used are SAPS, APACHE II and OSF. The predictive value of these scoring systems seems acceptable provided the data are collected when ARF is diagnosed and not on the patients' admission. After years, the overall survival rate does not exceed 30% to 50%. Full renal recovery is observed in 1/3 to 2/3 of surviving patients and varies according to the type of nephropathy. The social and financial consequences of these results emphasize the importance of preventing ARF, especially in its iatrogenic form. PMID- 7984248 TI - [Late renal and hypertensive complications of extracorporeal lithotripsy. Myth or reality?]. AB - Extracorporeal shock wave lithotripsy (ESWL) has produced dramatic advances in the surgical management of urinary calculi. However this new procedure could induce deleterious effects as loss of renal function and hypertension. Animal studies show that ESWL induces focal areas of necrosis and subsequent fibrosis in renal tissue. In humans, imaging technics demonstrate renal alterations in 80% of the patients. Acute renal hemodynamic and functional changes is frequent but transient in most of the cases. Some studies have shown a tendancy to an increase in blood pressure related to a decrease in renal plasma flow in one study. However most of these results are based on retrospective surveys of blood pressure and renal function. Therefore prospective clinical trials are needed to investigate the important questions of ESWL-induced hypertension and decrease renal function. PMID- 7984249 TI - [Crescentic glomerulonephritis and primary Gougerot-Sjogren syndrome]. AB - Glomerulonephritis complicating primary Gougerot-Sjogren's syndrome is extremely rare. We report the case of a 72-year old woman with primary Gougerot-Sjogren syndrome complicated by progressive renal failure. Kidney biopsy revealed a crescentic glomerulonephritis. A rapid improvement occurred with corticosteroids. This observation is, at our knowledge, the first case of crescentic glomerulonephritis described during this disease. A review of the literature concerning glomerulonephritis complicating primary Gougerot-Sjogren syndrome is reported. PMID- 7984250 TI - [Ectopic parathyroid gland discovered at physical examination]. PMID- 7984251 TI - [Role of tubular Na-K-ATPase in nephrotic syndrome induced by puromycin in the rat]. AB - Na-K-ATPase is an ubiquitous enzyme involved in the tubular reabsorption process. Na-K-ATPase is specifically controlled in each nephron segment. Sodium retention is one of the main features of the nephrotic syndrome. Hypervolemia is found in most of the nephrotic syndromes in adults, suggesting a primary renal origin. In the puromycin-induced nephrotic syndrome in rats, the collecting duct is the site of sodium retention. We have shown that Na-K-ATPase activity is specifically enhanced in collecting ducts from rats with puromycin-induced nephrotic syndrome. The stimulation of Na-K-ATPase activity was independent of aldosterone and endogenous inhibitors of the Na-K-ATPase, suggesting a primary paracrin or cellular mechanism. We have demonstrated that two different isoforms of the Na-K ATPase are coexpressed all along the rat nephron. In the puromycin-induced nephrotic syndrome, the activity of one isoform is specifically enhanced. These results demonstrate that the different isoforms of the Na-K-ATPase can be individually controlled. PMID- 7984252 TI - [The thick ascending limb of the loop of Henle: a key segment in the renal regulation of acid-base status?]. AB - The thick ascending limb (TAL) of rat kidney has been shown to reabsorb bicarbonate and NH4+. Therefore, in vivo and in vitro studies have demonstrated that bicarbonate absorption by the medullary TAL (mTAL) is influenced by peptide hormones (AVP, PTH), prostaglandin, osmolality and chronic metabolic acidosis. AVP, whose major effect is water balance regulation, also modulates acid-base handling in the mTAL, and then contribute to the regulation of renal acid excretion. These data suggest that the TAL could play an important role in the physiology and pathology of acid-base status. PMID- 7984253 TI - A single cell gel electrophoresis technique for the detection of DNA damage induced by ACNU, an alkylating agent or irradiation in murine glioma cell lines. AB - A simple and convenient technique for in situ quantification of DNA damage induced by 1-(4-amino-2-methyl-5-pyrimidinyl) methyl-3-(2-chloro-ethyl)-3 nitrosourea hydrochloride (ACNU) an alkylating agent, or irradiation was demonstrated in C6 glioma cells using a single cell gel electrophoresis. Treatment with ACNU or irradiation caused a dose dependent DNA damage which was detected by measuring the length of migration of fragmentary DNA in individual cells. Wild type C6 cells treated with ACNU (0, 10, 30, 60 micrograms ml-1) for one hour showed longer distance of migration of DNA than the ACNU-resistant subtype cells (C6R), indicating that ACNU-sensitive C6 cells were more vulnerable to ACNU than C6R cells. The results of DNA migration in C6 and C6R cells treated with ACNU were consistent with that from MTT assay which had been regarded as a standard method for chemosensitivity test. Furthermore, a time course study for DNA repair activity of C6 and C6R cells was also performed by measuring the length of DNA migration after incubation (0, 15, 30, 60, 120 min) of cells treated with 60 micrograms ml-1 ACNU. C6R cells repaired DNA damage more rapidly than C6 cells. In addition, the technique was also used to measure the DNA damage in C6 cells exposed to 0, 2, 6, 8, 10 Gy of x-ray irradiation, and a dose dependent DNA migration after radiation injury was observed. This technique appears to be simple and useful for assessing chemosensitivity or radiosensitivity in individual glioma cells. PMID- 7984254 TI - Neuropsychiatric sequelae of ischaemic cerebrovascular disease: clinical and neuroanatomic correlates and implications for the concept of dementia. AB - Neuropsychiatric disturbances along the continuum of cognitive disturbances in ischaemic cerebrovascular disease are reviewed and their neuroanatomic correspondences are explored. Depression, apathy, disinhibition, and delusions are common in ischaemic, cerebrovascular disease. Delirium, hallucinations, confabulations, akinesia, pathological affect, anxiety, and catastrophic reaction are less common, while manic syndromes appear rarely. Many of these neuropsychiatric syndromes remain poorly delineated. The presence of neuropsychiatric disturbance may not be correlated with the degree of cognitive disturbance. The implications of this finding for the concept of dementia are explored. The authors conclude that neuropsychiatric disturbances should be considered essential features of dementia. PMID- 7984255 TI - Microcystic meningioma: clinicopathological features of 6 cases. AB - The clinical and morphological features of 6 patients with unusual meningiomas with extensive microcystic formation are presented. There were 4 males and 2 females, ranging in age from 30 to 64 years. The clinical and neuro-imaging features of these tumours were identical with those of meningiomas in general. Morphological examinations disclosed that the tumour cells in 4 cases had many ultrastructural characteristics in common with the arachnoid cap cells, viz. prominent and complex interdigitation of the fine cytoplasmic processes, many desmosomes, and intracytoplasmic microfilaments. In contrast, the tumour cells of 2 cases had characteristic structures in common with trabecular arachnoid cells, viz. stellate in shape, a small number of intracytoplasmic filaments, relatively thick cytoplasmic processes, and occasional desmosomes. The tumour cells in these 2 cases were considered to recapitulate the subarachnoid structure and showed microcystic appearance. Although the histogenesis of microcysts in meningiomas is considered not to be uniform, the biological behaviour of these 6 tumours corresponded to those of meningiomas in general. PMID- 7984256 TI - Subcellular localization and cellular pharmacokinetics of MX2, a new morpholino anthracycline in glioma cells using confocal laser scanning microscopy. AB - The cellular uptake, subcellular distribution and retention of MX2, a new morpholino anthracycline, were compared with those of adriamycin (ADM) using confocal laser scanning microscopy (CLSM) in rat C6 and human T98G glioma cell lines. The tumor cells were exposed to 1-30 micrograms ml-1 of MX2 and ADM for 120 min and further incubated without drugs for 120 min after washing twice with medium. During incubation, real-time subcellular distribution of MX2 and ADM in living tumour cells were observed at various intervals using CLSM. For analysis of the in vivo uptake. Wistar rats bearing the C6 glioma were intravenously administered MX2 at a dose of 5 mg per kg body weight 60 min before sacrifice. The fluorescence of MX2 was predominantly seen in the cytoplasm in both C6 cells and T98G cells, although it was also present in the nucleus. In contrast, that of ADM was mainly confined to the nucleus in both cell lines. The fluorescent intensity of ADM in the nucleus after 120 min of exposure was approximately 1.5 fold higher than that of MX2 at the same dose exposure, probably indicating a greater amount of ADM accumulated in the nucleus than MX2. The influx and efflux of MX2 were much more rapid and greater than those of ADM in both cell lines. There was almost no difference in subcellular distribution among the doses tested in this study. The subcellular distribution of MX2 in vivo was almost similar to that of MX2 in vitro. These results suggest other mechanisms by which MX2 exerts its cytotoxic effects on tumour cells together with the inhibition of DNA topoisomerase II, which has been reported previously. It is considered that the CLSM technique is useful for the study of the cellular pharmacokinetics of antitumour agents such as anthracycline derivatives. PMID- 7984257 TI - Intraoperative CT scan findings during resection of glial tumours. AB - Intraoperative computerized tomographic (CT) scan findings in two cases during resection of glial tumor are described. These intraoperative CT images were obtained by an exclusively developed operating CT scanner system for use in the operating room. Repeated intraoperative CT scans taken during tumor removal showed shift of the brain including central structures and displacement of the cortical subarachnoid space in both cases. With contrast medium, the edge of the surrounding brain after resection was enhanced and a round enhanced area was observed in distant white matter. The distant enhancement, which we call 'remote enhancement', probably suggests damage to the blood-brain barrier due to surgical manoeuvre. PMID- 7984258 TI - Effect of 21-aminosteroid pretreatment in compression trauma to the spinal cord. AB - The present work was performed to establish whether pre-injury administration of the 21-Aminosteroid, U-74389F, is beneficial for treatment of acute spinal cord trauma in rats, as it has been demonstrated that the bolus administration of the same compound one hour after injury facilitates the return of the spinal cord function as measured by electrophysiological recordings in this compression animal model of spinal cord trauma. Cortical somatosensory evoked potentials (CSSEPs) were recorded as an indicator of spinal cord function before and after a severe compression injury. Vital signs and the CSSEPs were monitored up to five hours post-injury. U-4389F treatment was given as a single injection (15 mg kg-1) one hour prior to the injury which was followed by a continuous infusion (3 mg kg 1h-1) during the procedure. The CSSEPs were abolished immediately after this injury both, in the untreated and treated animal groups. The majority of the treated animals (80%) demonstrated recovery of the CSSEPs within the second hour post-injury. The control group showed 40% recovery at this time period. At five hours post-injury, recovery rates were 47% and 87% for control and treated groups respectively. We conclude that the administration of the 21-Aminosteroid, U74389F, one hour prior to spinal cord injury facilitates the return of spinal cord function as measured by CSSEPs in a compression rat model of acute spinal cord trauma, supporting and verifying our previous experiences using the same compound as i.v. bolus injections one, two and three hours after the trauma, respectively. PMID- 7984259 TI - Microsurgical anatomy of the trigeminal nerve. AB - We studied the trigeminal nerve in the middle cranial fossa in 20 cadaveric specimens (10 fixed skull base). Specifically, we analysed the relationships among the gasserion or trigeminal ganglion (herein referred to as the gasserion ganglion), the internal carotid artery, and the petrous bone. The dimensions of the trigeminal ganglia, the length from the ganglia to the exit foramina, and the width of the ophthalmic, maxillary, and manidibular nerves were also studied. The foramina of the middle cranial fossa were measured for their diameter and their distance from each other. Our paper compares our study to previous studies and the measurements taken in those studies. The lesions affecting the ganglion and the nerves are discussed and the surgical approaches to the middle cranial fossa, the petrous bone, and the upper clivus are also reviewed. PMID- 7984260 TI - Chronic vascular irritation of the facial nerve causes facial spasm in rats. AB - The abnormal muscle response, elicited by electrical stimulation of one branch of the facial nerve and recorded from muscles innervated by another branch, has been used previously as an objective sign of hemifacial spasm in the development of animal models of this disorder. In the present study we recorded spontaneous electromyographic activity from the orbicularis oculi muscle from both sides in rats in which a demyelination of the peripheral portion of the facial nerve and vascular contact had been made previously. The root mean square value of the electromyographic activity on the affected side was significantly larger than that on the unaffected side in all rats in which the vascular irritation had caused the abnormal muscle response to appear. The results support our earlier finding that vascular contact together with demyelination of the peripheral facial nerve can cause the development of signs of hemifacial spasm, including involuntary muscle contractions. PMID- 7984261 TI - Local cerebral blood flow and glucose metabolism in chronic focal ischaemia of stroke-prone spontaneously hypertensive rats. AB - The relationship between local cerebral blood flow (ICBF) and local cerebral glucose metabolism (ICGU) at the chronic stage of focal cerebral ischaemia was assessed in young stroke-prone spontaneously hypertensive rats (SHRSP) following occlusion of the distal middle cerebral artery (MCA). On day 7 following this occlusion, ICBF and ICGU were measured by autoradiographic methods using 14C iodoantipyrine and 14C-2-deoxyglucose (2DG), respectively. The infarct was limited to the ipsilateral cerebral cortex. A narrow band of increased uptake of 14C-2DG was observed in the border zone at the periphery of infarcted areas. The ICBF in the ischaemic cortex revealed a graded reduction from the ischaemic centre to the surrounding tissues. A significant reduction in ICGU coupled to CBF was also observed in 4 of 13 selected noninfarcted regions ipsilateral to the MCA occlusion. The ischaemic regions had a significant increase in water content. The region with ischaemic oedema was limited to a narrow area compared with the findings regarding ICBF and ICGU. The SHRSP strain has more severe cerebral ischaemia, oedema formation, and metabolic derangement at the chronic stage of focal ischaemia, compared to normo-tensive animals. PMID- 7984262 TI - Morphological characterization of dorsal horn spinal neurons in rats with unilateral constriction nerve injury: a preliminary study. AB - A new animal model of neuropathic pain utilizing loose ligation of a peripheral nerve has been previously reported. In addition to displaying abnormal pain symptoms such as allodynia and hyperalgesia, physiologic and morphologic changes are seen in spinal cord dorsal horn neurons. Two weeks after ligation of the right common sciatic nerve, rat dorsal horn spinal cord neurons with signs of transsynaptic changes (dark neurons) were found on the side ipsilateral to the nerve injury. A few dark neurons were also found in the contralateral dorsal horn. The distribution of dark neurons in lumbar dorsal horn was limited to the superficial laminae (I-III). The following changes which suggest altered cellular activity were seen under the electron microscope. The nuclear envelope appeared ruffled while the mitochondria appeared normal. In addition, the dense cytoplasm was filled with rosettes of ribosomes as well as extensively developed rough endoplasmic reticulum and distended Golgi apparatus cisternae. While dark neurons had normal appearing somatic synapses, a few appeared atypical. The altered activity of these neurons may lead to abnormal sensory experiences and may be a consequence of central changes in response to persistent peripheral nerve injury. The purpose of the present study was to assess morphologic, hence functional, changes in spinal cord neurons in response to peripheral nerve constriction injury which evokes chronic pain-related behaviour. PMID- 7984263 TI - Immunohistochemical localization of basic fibroblast growth factor in choroid plexus of the rat. AB - In the present study, we report that an intense bFGF-immunoreactivity has been detected in the choroid plexus of the brain ventricles of adult rats. These results suggest that epithelial choroid plexus cells may be the source of the cerebrospinal fluid bFGF. PMID- 7984264 TI - Anaplastic ganglioglioma: case report and review of the literature. AB - We present the case of a 13-year-old boy who had a 12 year history of complex partial seizures. Recent CT scan and Magnetic Resonance Imaging (MRI) showed a contrast-enhancing lesion of the left temporal lobe, while CT performed 6 years ago was unconspicuous. Extended lesionectomy was performed according to the results of presurgical epileptological evaluation. Histological examination of the specimen showed an anaplastic ganglioglioma (WHO grade III). The clinical, neuroradiological, and histopathological findings of our patient are presented with respect to the literature on malignant gangliogliomas. PMID- 7984265 TI - Hemifacial spasm and cerebellopontine angle epidermoid: case report and review. AB - A case with hemifacial spasm with tinnitus due to right cerebellopontine angle epidermoid is reported. The tumour was supposed to have caused the displacement of the part of anterior inferior cerebellar artery in the vicinity of the root exit zone of the ipsilateral facial nerve. Near total removal of the tumour along with microvascular decompression was done and the patient was completely relieved of his symptoms. The incidence of hemifacial spasm due to cerebellopontine angle epidermoid is extremely low. The cause of such an association is discussed and relevant literature is reviewed. PMID- 7984266 TI - Receptors for 5-hydroxytryptamine: current perspectives on classification and nomenclature. AB - With the increasing number of 5-HT receptors recently identified, using molecular biology techniques, the classification of 5-HT receptors is under review. An integrated approach is proposed to include operational and transductional as well as structural criteria for definitive receptor characterization. On this basis the existence of as many as seven classes of 5-HT receptor are recognized although only the 5-HT1, 5-HT2 and 5-HT3 receptor classes are well defined. PMID- 7984267 TI - Molecular biology of 5-HT receptors. PMID- 7984268 TI - The molecular evolution of G protein-coupled receptors: focus on 5 hydroxytryptamine receptors. AB - Phylogenetic comparisons between homologous proteins can provide information on the rates of molecular evolution of the proteins. G protein-coupled receptors are a "superfamily" of proteins which exist in species ranging from yeast to man. Based on an analysis of the percentage of amino acid homology between various species, the rate of molecular evolution of G protein-coupled receptors can be estimated at approx 1% per 10 million years. Based on this assumption, the primordial 5-HT receptor must have evolved more than 700-800 million years ago since the 3 major classes of G protein-coupled 5-HT receptors (i.e. 5-HT1, 5-HT2 and 5-HT6 receptors) are less than 25% homologous. 5-HT5, 5-HT7, 5-HTsnail, 5 HTdro and 5-HT1A receptors differentiated approx 600-700 million years ago, the time period during which vertebrates diverged from invertebrates. The mammalian 5 HT receptor subtypes have differentiated over the past 90 million years. Thus, although a recent flurry of "new" 5-HT receptors have appeared in the literature, the first "primordial" 5-HT receptor evolved over 750 million years ago, a date which likely predates the evolution of muscarinic, dopaminergic and adrenergic receptor systems. This analysis also predicts that a significant number of both mammalian and invertebrate G protein-coupled 5-HT receptor subtypes remain to be identified. PMID- 7984269 TI - The ontogeny of tolerance to the 5-HT1A agonist 8-OH-DPAT: a study in the rat. AB - The 5-HT1A receptor agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) induces hypothermia and a flat body posture in rats. Tolerance to 8-OH-DPAT develops in adult rats with regard to these responses. The ontogeny of the ability to induce tolerance to the hypothermia and the flat body posture elicited by 8-OH-DPAT was studied. Rat pups of both sexes were given 8-OH-DPAT, 100 micrograms/kg (0.352 mumol/kg) or saline for 1, 4 or 12 days between 22 and 34 days of age. At 26 days of age no attenuation was induced by treatment during the previous 4 days. In contrast, at 34 days of age there was a clear attenuation of both responses induced by 8-OH-DPAT after an analogous 4 day treatment. The data indicate that the ability to induce tolerance to 8-OH-DPAT is not developed before 26 days of age in the rat. PMID- 7984270 TI - Lack of 5-HT1A autoreceptor desensitization following chronic citalopram treatment, as determined by in vivo microdialysis. AB - Electrophysiological studies suggest that 5-HT autoreceptor desensitization may be responsible for the delayed clinical efficacy of some antidepressant drugs, such as selective 5-HT reuptake inhibitors (SSRI) and certain MAO inhibitors (MAOI). In the present study we have used in vivo microdialysis to test this hypothesis. Rats were treated for 2 weeks with the antidepressant SSRI citalopram (5 mg/kg, s.c., b.i.d.). After 24 hr withdrawal, dialysis probes were implanted in the dorsal hippocampus (DH) and the frontal cortex (FCx). The rats then received as acute challenge, a 5-HT1A autoreceptor-active dose of the reference 5 HT1A agonist 8-OH-DPAT (0.025 mg/kg s.c.). The 8-OH-DPAT-induced changes in dialysate 5-HT from the DH and the FCx were monitored and taken as an index of autoreceptor sensitivity. Chronic citalopram and control animals responded similarly to 8-OH-DPAT with a drop of 5-HT of about 50-65%; no significant difference between the chronic citalopram and control groups were obtained, either in the DH or in the FCx. These data suggest that cell body 5-HT1A autoreceptors do not desensitize in response to repeated administration with antidepressant SSRI drugs such as citalopram. PMID- 7984271 TI - Repeated cocaine exposure inhibits the adrenocorticotropic hormone response to the serotonin releaser d-fenfluramine and the 5-HT1A agonist, 8-OH-DPAT. AB - The influence of cocaine exposure on serotonergic neurons and postsynaptic 5-HT1A receptor-mediated responses was evaluated by measuring neuroendocrine responses to a serotonin (5-HT) releaser or a 5-HT1A agonist. Male rats received cocaine (15 mg/kg, i.p.) or saline twice daily for 7 days. Forty-two hr after the final cocaine injection, the 5-HT releaser d-fenfluramine (0, 0.2, 0.6, 2, or 5 mg/kg, i.p.) or the 5-HT1A agonist, 8-OH-DPAT (0, 10, 50, 200 or 500 micrograms/kg, s.c.) were administered. Blood samples were then collected for analysis of plasma ACTH, prolactin, and renin concentrations. The ACTH responses to d-fenfluramine and 8-OH-DPAT were inhibited in cocaine pretreated rats. However, the prolactin responses to d-fenfluramine and 8-OH-DPAT were not significantly modified by cocaine exposure. Additionally, the renin response to d-fenfluramine was unaltered by repeated cocaine administration, while 8-OH-DPAT did not alter renin secretion in either pretreatment group. In contrast to published reports which show that cocaine exposure produces supersensitive 5-HT2A and/or 5-HT2C receptor mediated responses, the present data suggest that repeated cocaine exposure produces subsensitivity to at least some postsynaptic 5-HT1A receptors. Cocaine induced deficits in the ACTH response to 5-HT releasers may reflect 5-HT1A receptor subsensitivity, but presynaptic deficits cannot be excluded. Examination of the ACTH response to 5-HT1A agonists may represent a valuable approach to determine deficits in 5-HT function in human cocaine abusers. PMID- 7984272 TI - Contrasting behavioural effects of 8-OH DPAT in the dorsal raphe nucleus and ventral hippocampus. AB - Administration of the 5-HT1A receptor agonist (+-)-8-Hydroxy dipropylaminotetralin (8-OH DPAT, 50 ng) into the dorsal raphe nucleus (DRN) increased social interaction but did not change the motor activity of rats tested in high light, thus indicating an anxiolytic response. This effect was blocked by coadministration of the 5-HT1A antagonist, tertatolol (3 micrograms). In contrast, 8-OH DPAT (50 and 100 ng) was without effect on social interaction when administered to the DRN projection area in the ventral hippocampus, but did change locomotor activity. The effects depended on the light level and dose: thus when the rats were tested in low light, 50 ng increased locomotor activity, but in high light a decrease was found with 100 ng and also an induction of wet dog shakes. Thus, our results support the importance of the somatodendritic autoreceptors in the DRN in alleviating anxiety, whereas the post-synaptic receptors in the ventral hippocampus play no role. They do, however, mediate changes in activity and the 5-HT syndrome. PMID- 7984273 TI - Median and dorsal raphe injections of the 5-HT1A agonist, 8-OH-DPAT, and the GABAA agonist, muscimol, increase voluntary ethanol intake in Wistar rats. AB - Low doses of the selective 5-HT1A agonist 8-OH-DPAT increase ethanol intake in a limited access paradigm following peripheral injection. This may be due to a reduction in 5-HT neurotransmission following activation of raphe somatodendritic autoreceptors. In order to test this hypothesis, and to determine the effects of selective reductions in raphe 5-HT activity, experiments examined the effects of injecting 8-OH-DPAT into the dorsal raphe (0, 0.02, 0.1, 1 and 2.5 micrograms) or the median raphe (0, 0.1, 1 and 5 micrograms) in rats trained to drink 12% ethanol for 40 min each day. The effects of the GABAA agonist, muscimol, on ethanol intake were also examined. Ethanol intake was increased at the highest dose of 8-OH-DPAT following injection into either site, with no change in water intake. Thus, the effects of 8-OH-DPAT are selective for ethanol. The selective 5 HT1A antagonist, (+)-WAY100135 (0.3, 1 and 3 mg/kg), blocked the effect of 8-OH DPAT, showing that activation of 5-HT1A receptors underlies the ethanol drinking induced by 8-OH-DPAT. These results are consistent with the idea that reduced 5 HT function increases ethanol intake. Several behavioral mechanisms for this effect are discussed. Muscimol (50-100 ng) also increased ethanol drinking. Following injection into the median raphe, muscimol also stimulated water intake. These effects are probably due to non-specific behavioural activation induced by this treatment. However, the effect of muscimol in the dorsal raphe was specific for ethanol since water intake was not altered.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7984274 TI - In vivo characterization of the putative 5-HT1A receptor antagonist SDZ 216,525 using two models of somatodendritic 5-HT1A receptor function. AB - SDZ 216,525 has been proposed to be a silent 5-HT1A receptor antagonist. The present study examined the potential intrinsic agonist action of SDZ 216,525 using two in vivo models of somatodendritic 5-HT1A autoreceptor function: 5-HT release using microdialysis and feeding behaviour of satiated animals. SDZ 216,525 (1 mg/kg s.c.) and the alpha 1-adrenoceptor antagonist prazosin (1 mg/kg s.c.) significantly decreased hippocampal 5-HT release. In addition, SDZ 216,525 (3 and 10 mg/kg s.c.) and prazosin (3 and 10 mg/kg s.c.) significantly increased food intake in satiated rats. The selective 5-HT1A receptor antagonist (RS) WAY100135 (10 mg/kg s.c.) which has been demonstrated to block the effects of 8 OH-DPAT on 5-HT release and food intake had no significant effect on the response induced by SDZ 216,525. In contrast, the non-selective 5-HT1A receptor antagonist (-)-pindolol (8 mg/kg s.c.) attenuated both SDZ 216,525 responses. The decrease in hippocampal 5-HT release and increase in food intake induced by SDZ 216,525 suggest that the compound may be a 5-HT1A receptor partial agonist. However, the failure of the 5-HT1A receptor antagonist (RS)-WAY100135 to block the SDZ 216,525 responses suggests that SDZ 216,525 decreases 5-HT release and increases food intake by a mechanism other than 5-HT1A receptor agonism. The high affinity of SDZ 216,525 for the alpha 1-adrenoceptor, and the ability of prazosin to decrease 5-HT release and increase food intake, suggest that the effects of SDZ 216,525 may be mediated via an alpha 1-adrenoceptor antagonist action. PMID- 7984275 TI - Localization of 5-HT1B, 5-HT1D alpha, 5-HT1E and 5-HT1F receptor messenger RNA in rodent and primate brain. AB - In situ hybridization histochemistry (ISHH) was used to study the distribution of various 5-HT1 receptor messenger RNAs (mRNA) in the mammalian nervous system. Since the cDNAs encoding the different 5-HT1 receptors, have not been cloned in one single species, brains of the species appropriate for the 5-HT1 receptor messenger RNA (mRNA) have been used. Thus, 5-HT1B and 5-HT1D alpha mRNA were determined in rat and mouse brain, while 5-HT1E and 5-HT1F mRNA were studied in human (and monkey) and guinea-pig brain, respectively. 5-HT1B and 5-HT1D alpha hybridization signals were predominantly present in caudate-putamen and cortical areas; in addition, 5-HT1B mRNA was also detected in hippocampus, cerebellum and cerebral arteries. In general, the distribution of 5-HT1B mRNA was characterized by high densities, whereas 5-HT1D alpha mRNA was expressed at very low levels. Comparison of the localization of the mRNAs to the regional distributions of the 5-HT1B and 5-HT1D binding sites in rat brain (described in a previous study), revealed that both receptor subtypes could be putative presynaptic heteroreceptors, modulating the release of various neurotransmitters in the central nervous system. The mRNA encoding the recently cloned 5-HT1E receptor, which has low affinity for the 5-HT1 receptor ligand 5-carboxamidotryptamine (5 CT), was localized in human brain. It was found to be present in cortical areas, caudate, putamen and amygdala, areas known to contain 5-CT insensitive 5-HT1 binding sites. The regional distribution of the 5-HT1F mRNA was determined in guinea-pig brain: high densities were observed in various cortical areas, the hippocampal formation and claustrum, which are regions known to contain 5-CT insensitive 5-HT1 or non 5-HT1A/1B/IC/ID [3H]5-HT binding sites. Altogether, this ISHH study describes the distribution of mRNAs of recently cloned 5-HT1 receptors in rodent and primate brain and compares these results to the distribution of the heterogeneous population of 5-HT1 binding sites. PMID- 7984276 TI - A single point mutation increases the affinity of serotonin 5-HT1D alpha, 5-HT1D beta, 5-HT1E and 5-HT1F receptors for beta-adrenergic antagonists. AB - The serotonin 5-HT1B and 5-HT1A receptors bind certain beta-adrenergic antagonists, such as propranolol and pindolol, with high affinity. Other 5-HT1 receptors that display very low affinity for beta-adrenergic antagonists, have either a threonine (T) (5-HT1D alpha, 5-HT1D beta and 5-HT1E) or an alanine (A) (5-HT1F) residue in the homologous position in the seventh transmembrane domain. In the case of the human 5-HT1D beta receptor, replacement of this T with asparagine (N), dramatically increases its ability to bind beta-adrenergic antagonists. To assess whether other 5-HT1 receptors would behave similarly, we have used site-directed mutagenesis to replace the T or A in 5-HT1D alpha, 5-HT1E and 5-HT1F receptors with N. Both the wild-type and mutant genes were expressed transiently in COS-7 cells and radioligand binding studies were performed by using [3H]5-HT and [125I]iodocyanopindolol. Using [3H]5-HT, we found that the affinities of all the mutant receptors for propranolol and pindolol were significantly increased by 100-1000 fold, 5-HT1D alpha and 5-HT1F receptors showing the highest and the 5-HT1E receptor displaying the lowest affinity. On the other hand, the affinities for 5-HT were essentially unchanged as compared to the wild-type receptors. All mutant receptors bound [125I]iodocyanopindolol with high affinity, KD values ranging between 0.04 nM (mutant 5-HT1D alpha) and 0.57 nM (mutant 5-HT1E), whereas the wild-type receptors failed to show any specific binding with this radioligand in the same concentration range used for the mutant receptors.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7984277 TI - 5-HT1D as well as 5-HT1A autoreceptors modulate 5-HT release in the guinea-pig dorsal raphe nucleus. AB - 5-Hydroxytryptamine (5-HT) release was measured by fast cyclic voltammetry in guinea-pig dorsal raphe nucleus slices. Release was reproducibly evoked by a single 0.1 msec pulse of electrical stimulation. The 5-HT1A receptor agonist 8 hydroxy-2-(di-n-propylamino) tetralin (8-OH DPAT) produced a concentration related inhibition of the stimulated 5-HT release, with 50% inhibition at 47 nM. This inhibition was competitively antagonized by N-tert-butyl 3-4-(2 methoxypheny)piperazin-1-yl-2- phenylpropanamide dihydrochloride [(+/-)WAY 100135], a selective 5-HT1A receptor antagonist (pA2 = 7.9). The 5-HT1D receptor agonist sumatriptan also produced a concentration-related inhibition of 5-HT release, with 50% inhibition at 40 nM. The effect of sumatriptan on 5-HT release was antagonized by the 5-HT1D receptor antagonist 2'-methyl-4'-(5-methyl [1,2,4]oxadiazol-3-yl)-biphenyl-4-carboxyli c acid [4-methoxy-3-(4-methyl piperazin-1-yl)-phenyl]-amide (GR127935) (pA2 = 8.7). Both (+/-)WAY 100135 and GR127935 increased the 5-HT release evoked by a train of 5 pulses at 1 Hz, suggesting that they were antagonizing the feedback of endogenously released 5-HT onto its autoreceptors. These findings demonstrate for the first time the presence of functional 5-HT1D as well as 5-HT1A autoreceptors in the guinea-pig dorsal raphe nucleus. PMID- 7984278 TI - The cloned human 5-HT1E receptor couples to inhibition and activation of adenylyl cyclase via two distinct pathways in transfected BS-C-1 cells. AB - The pharmacological profile of coupling of the cloned human serotonin [5 hydroxytryptamine] (5-HT)1E receptors to second messengers was studied in African green monkey kidney cells (BS-C-1). At low concentrations (0.1-100 nM), 5-HT inhibited forskolin-stimulated cAMP accumulation (FSCA) by up to 90% whereas at higher concentrations it potentiated FSCA; potentiation was dependent on receptor density. Pretreatment of cells with pertussis toxin (PTx) or cholera toxin (CTx) eliminated agonist-induced inhibition and potentiation of FSCA, respectively. The potentiation of FSCA was not due to activation of phospholipase C and/or phospholipase A2 since 5-HT had no effect on inositol phosphate release, intracellular Ca2+ mobilization or arachidonic acid mobilization; neither was it affected by pretreatment with the nonselective phospholipase A2 inhibitor, quinacrine, or by the removal of extracellular Ca2+. The pharmacological profiles of the 5-HT1E receptor-mediated inhibition and potentiation of FSCA were very similar, although agonists displayed higher affinity for the former. These results indicate that the human 5-HT1E receptors can potentially couple, with similar pharmacological profiles, to multiple effector pathways. However, the potency and intrinsic activity of the compounds eliciting these responses can differ significantly, depending on the receptor density and the effector pathway studied. PMID- 7984279 TI - Biochemical evidence for the regulation of central noradrenergic activity by 5 HT1A and 5-HT2 receptors: microdialysis studies in the awake and anaesthetized rat. AB - Here we have studied the effect of various 5-HT1A and 5-HT2 receptor-selective drugs on noradrenaline release in the hippocampus on anaesthetized and awake rats using microdialysis. In the anaesthetized rat, administration of the 5-HT1A agonists buspirone, gepirone and ipsapirone increased noradrenaline levels in the microdialysates. However, the common metabolite of these compounds, 1-PP (an alpha-2 adrenoceptor antagonist with low affinity for 5-HT1A receptors), also increased noradrenaline efflux whilst the 5-HT1A receptor agonist 8-OH-DPAT and MDL 73005EF, which are not metabolized to 1-PP, did not. In the awake rat, buspirone but also 8-OH-DPAT increased noradrenaline efflux. A similar effect was observed in response to MDL 73005EF and the 5-HT1A ligand NAN-190. Since the latter two drugs have weak intrinsic activity at the post-versus presynaptic 5 HT1A receptor, a presynaptic mechanism (inhibition of 5-HT release) was implicated. The 5-HT2 receptor may be important to this mechanism as noradrenaline increased following administration of the 5-HT2 receptor antagonists, ritanserin and ICI 170,809. In conclusion, our data indicate that there are clear differences in the effects of 5-HT1A and 5-HT2 receptor-selective drugs on noradrenaline efflux in hippocampus of the anaesthetized versus awake rat. Our findings are reconcilable with the hypothesis that in the awake (but not anaesthetized) rat, release of noradrenaline in hippocampus is influenced by an inhibitory tone mediated via 5-HT2 receptors. If this inhibitory tone is removed, either by decreasing 5-HT release through activation 5-HT1A autoreceptors or by blocking postsynaptic 5-HT2 receptors, noradrenaline release increases. PMID- 7984280 TI - Differential effects of N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline (EEDQ) on various 5-HT receptor binding sites in the rat brain. AB - The effects of N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline (EEDQ), an alkylating agent producing irreversible blockade of various membrane bound receptors in brain, were investigated on four different types of serotonin receptors, 5-HT1A, 5-HT1B, 5-HT2A and 5-HT3, in various brain regions in the rat. In addition, the fate of central benzodiazepine- and "R"-zacopride-specific binding sites was also examined in rats treated with EEDQ. Membrane binding assays and/or quantitative autoradiography with appropriate radioligands indicated that EEDQ inactivated 5-HT1A, 5-HT1B and 5-HT2A sites, but was poorly active on 5-HT3, benzodiazepine and "R" sites. Among the receptors affected by EEDQ, hippocampal 5-HT1A sites were the most sensitive to the alkylating agent (ID50 approximately 1 mg/kg i.p.), followed by the cortical 5-HT2A (ID50 approximately 3 mg/kg i.p.) and the striatal 5-HT1B (ID50 approximately 6 mg/kg i.p.) sites. Pretreatment by selective ligands partially protected hippocampal 5 HT1A sites from irreversible inactivation by EEDQ (10 mg/kg i.p.) with the following order of efficacy: WAY 100635 > spiperone > BMY 7378 > ipsapirone. Similarly, pretreatment by spiperone (5 mg/kg i.p.) also reduced the ability of EEDQ to inactivated cortical 5-HT2A receptors. Analyses of the time-course recovery of respective binding sites after EEDQ administration showed that the turnover rate of 5-HT1A sites did not significantly differ in the dorsal raphe nucleus and in various forebrain areas (hippocampus, septum, cerebral cortex; half-life: approximately 4 days), but was lower than that of cortical 5-HT2A sites (half-life: 2.9 days). PMID- 7984281 TI - Lack of effect of antidepressant drugs on the levels of mRNAs encoding serotonergic receptors, synthetic enzymes and 5HT transporter. AB - Serotonergic transmission is thought to be central to the aetiology of depression and the therapeutic actions of antidepressant drugs, and the latters' delayed effect has given rise to the hypothesis that an adaptive change may be involved, possibly at the level of gene expression. We have examined this hypothesis by treating rats over a time course of up to 32 days with either imipramine, mianserin, fluvoxamine, citalopram, amoxapine or saline and measuring the levels of mRNAs encoding the 5HT1A, 5HT1B, 5HT1C and 5HT2 receptors, the enzymes tryptophan hydroxylase and aromatic amino acid decarboxylase, and the 5HT transporter. None of the treatments gave rise to significant changes in any of the mRNA levels at any time point. These results suggest that the reported changes in 5HT receptor numbers do not occur as a result of changes in the abundance of their encoding mRNAs, and that changes to the latter is not central to the therapeutic effects of antidepressant drugs. PMID- 7984282 TI - Multiple serotonin receptor subtypes modulate prepulse inhibition of the startle response in rats. AB - The phenomenon of prepulse inhibition (PPI) of the acoustic startle reflex is widely used as an operational measure of sensorimotor gating mechanisms. Because sensorimotor gating abnormalities have been identified in schizophrenic patients, the exploration of the neural substrates involved in PPI may provide insight into the neural dysfunctions underlying this disorder. Both dopaminergic and glutamatergic systems are involved in the modulation of PPI in rats. In addition, the present studies demonstrate complex serotonergic influences in this phenomenon. Specifically, both the 5-HT2 agonist, DOI, (2,5-dimethoxy-4 iodoamphetamine), and the 5-HT1B agonist, RU 24969, [5-methoxy 3(1,2,3,6)tetrahydropyridin-4- yl]-1H-indole, potently and reversibly disrupted PPI. The 5-HT2C agonist mCPP, [1-(m)-chlorophenyl-piperazine], was ineffective. Furthermore, ketanserin (2.0 mg/kg) and haloperidol (0.1 mg/kg) but not (+/ )propranolol (20.0 mg/kg) blocked the effect of DOI. In addition, the same doses of haloperidol, and, to a lesser extent, (+/-)propranolol, prevented the disruption of PPI induced by RU 24969. Together with previous reports of 5-HT1A involvement in PPI, these results argue for multiple serotonergic mechanisms in the modulation of PPI. PMID- 7984283 TI - Effects of chlorisondamine and restraint on cortical [3H]ketanserin binding, 5 HT2A receptor-mediated head shakes, and behaviours in models of anxiety. AB - A recent study has indicated that ganglionic transmission mediates acute restraint-elicited increases in brain tryptophan (5-HT precursor) levels, 5-HT synthesis and (possibly) release. Because restraint-induced release of 5-HT has been shown to be associated with a paradoxical increase in cortical 5-HT2A receptor binding, we have examined the influence of 5-HT synthesis/release upon cortical 5-HT2A receptor binding and 5-HT2A receptor-mediated head shakes in 3-hr restrained rats pretreated with the ganglionic blocker chlorisondamine. In keeping with past reports regarding the effects of restraint and ganglionic blockade upon anxiety, we have also measured the behavioural effects of restraint and/or chlorisondamine in two animal models of anxiety, the elevated plus-maze and the social interaction test. Chlorisondamine pretreatment (2.5 mg/kg, 20 min beforehand) prevented restraint-elicited defaecation and body weight decreases. Although stress amplified the head shake response to the injection of the 5 HT2A/5-HT2C receptor agonist 1-(4-iodo-2,5-dimethoxyphenyl)-2-aminopropane (DOI, 1 or 2 mg/kg 2 hr after the end of restraint), cortical [3H]ketanserin binding remained unaltered. Chlorisondamine treatment was inactive, except for the amplification of the head shake response to DOI (2 mg/kg) in restrained rats. When exposed to the social interaction test, neither restraint nor chlorisondamine affected social interaction, locomotion, or rearings. In the elevated plus-maze, the percent number of open arms entered and the total number of arms entered were decreased by acute restraint, whilst chlorisondamine pretreatment was inactive. PMID- 7984284 TI - Evidence that mCPP-induced anxiety in the plus-maze is mediated by postsynaptic 5 HT2C receptors but not by sympathomimetic effects. AB - 1-(3-Chlorophenyl)piperazine (mCPP) (0.125-1.0 mg/kg i.p.), previously shown to inhibit social interaction, dose-dependently reduced exploration of the open arms of an elevated plus-maze. These findings suggest anxiogenic properties. The effect of mCPP was more potently inhibited by 1-(1-naphthyl)piperazine than by ketanserin, indicative of its mediation via activation of 5-HT2C rather than 5 HT2A receptors. The 5-HT1B receptor agonist CGS 12066B did not antagonise the anxiety-like response to mCPP, and further reduced exploration at the highest dose tested (10 mg/kg i.p.). Depletion of serotonin (5-HT) by p chlorophenylalanine (PCPA, 150 mg/kg/day x 3) did not prevent the response, although PCPA itself increased open arm exploration. The 5-HT1A/B and beta adrenoceptor antagonist 1-propanolol (5 mg/kg i.p.) and the peripheral beta 1 receptor antagonist atenolol (20 mg/kg i.p.) showed no significant activity on the plus-maze either alone or against the anxiogenic effect of mCPP. These results indicate that mCPP induces anxiety in the rat in the elevated plus-maze primarily by stimulation of postsynaptic 5-HT2C receptors, and suggest that sympathomimetic effects of mCPP are not involved. PMID- 7984285 TI - Slow wave sleep in humans: role of 5-HT2A and 5-HT2C receptors. AB - We studied the effects of the 5-HT2 receptor antagonists, ritanserin and ketanserin, on the sleep of healthy volunteers in order to clarify the role of 5 HT2A and 5-HT2C receptors in the regulation of slow wave sleep (SWS) in humans. Ritanserin, 5 mg, produced a substantially larger increase in SWS (51.4%) than either ketanserin, 20 mg (17.2%) or ketanserin, 40 mg (24.4%). Ritanserin has a significantly higher affinity than ketanserin for 5-HT2C receptor binding sites in the human brain and, based on estimates of per cent occupancy by the two compounds at brain 5-HT2A and 5-HT2C receptors, we conclude that SWS in humans is primarily regulated by 5-HT2C receptors. PMID- 7984286 TI - Pharmacological characterization of the apparent splice variants of the murine 5 HT3 R-A subunit expressed in Xenopus laevis oocytes. AB - The actions of 5-hydroxytryptamine3 (5-HT3) receptor agonists and antagonists have been determined on the recombinant murine 5-HT3 R-A and an apparent splice variant of this subunit, termed 5-HT3 R-AS. When expressed in Xenopus laevis oocytes, both forms of the subunit functioned as a homo-oligomeric complex and exhibited inward current responses to bath applied 5-HT. Analysis of the 5-HT concentration-response curve obtained with either homo-oligomer gave Hill coefficients greater than two, suggesting positive co-operativity within the receptor complex. The rank order of potency of a range of 5-HT3 receptor agonists [m-chlorophenylbiguanide > 5-HT > 2-methyl-5-HT (2-Me-5-HT) > or = phenylbiguanide] was identical for both subunits. Indeed, with the exception of 2 Me-5-HT, for the agonists tested there was little difference across the subunits in either their potency, or the maximal current response that they elicited relative to 5-HT. Although 2-Me-5-HT exhibited a similar potency for both subunits, the maximal response evoked by this agonist at the 5-HT3 R-AS subunit was much reduced when compared to the 5-HT3 R-A subunit. The 5-HT-induced current mediated by either form of the subunit was inhibited by the 5-HT3 receptor selective antagonists BRL 46470, granisetron and ondansetron and the non selective antagonists (+)-tubocurarine, metoclopramide and cocaine in a reversible and concentration-dependent manner. These antagonists did not discriminate between the subunits and their potencies were similar to those reported previously for 5-HT3 receptors native to murine neuronal cells.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7984287 TI - Serotonin3 receptor agonists attenuate glutamate-induced firing in rat hippocampal CA1 pyramidal cells. AB - The techniques of extracellular single cell recording and microiontophoresis were used to study the effect of 5-HT3 receptor agonists on glutamate-activated firing of CA1 hippocampal pyramidal cells. Iontophoretic application of 5-HT3 receptor agonists 2-methyl-5-HT and SR 57227A produced a current (dose)-dependent suppression of the firing of CA1 pyramidal cells; SR 57227A was more effective than 2-methyl-5-HT. The suppressant action of 2-methyl-5-HT and SR 57227A had a slow onset and showed little or no desensitization. This effect was markedly attenuated or completely blocked by the 5-HT3 receptor antagonist BRL 46470A but not by the nonspecific 5-HT1 and 5-HT2 receptor antagonist metergoline or by the 5-HT1A antagonist WAY 100478. Intravenous administration of SR 57227A was effective in reducing the firing rate of CA1 pyramidal cells and this effect was prevented by BRL 46470A administered either i.v. or iontophoretically. Iontophoresis of 2-methyl-5-HT also diminished CA1 postsynaptic field potentials evoked by electrical stimulation of the Schaffer collaterals. Again, BRL 46470A but not metergoline prevented the suppressant action of 2-methyl-5-HT. Taken together, our results indicate that activation of 5-HT3-like receptors in the hippocampal CA1 region effectively reduces the efficacy of glutamatergic neurotransmission. PMID- 7984288 TI - Chlorpromazine and QX222 block 5-HT3 receptors in N1E-115 neuroblastoma cells. AB - The effects of chlorpromazine and the lidocaine derivative QX222, which block nicotinic acetylcholine receptors, were examined on 5-HT3 receptors in N1E-115 mouse neuroblastoma cells, using whole cell voltage-clamp and radioligand binding. Electrophysiological studies examining the effects of chlorpromazine and QX222 on 5-HT3 agonist-induced responses revealed IC50s of 0.2 and 8.5 microM respectively. The action was not voltage- or use-dependent and there was no blocking action when chlorpromazine was applied from inside the cell. Chlorpromazine and QX222 inhibited the binding of a radiolabelled 5-HT3 receptor antagonist, [3H]GR65630, with IC50s of 0.9 and 29 microM respectively. Scatchard plots revealed a decrease in affinity (Kd) in the presence of chlorpromazine, but no change in the maximum number of binding sites (Bmax). The results suggest differential actions of the compounds at 5-HT3 and acetylcholine receptors. PMID- 7984289 TI - Interaction between enantiomers of mianserin and ORG3770 at 5-HT3 receptors in cultured mouse neuroblastoma cells. AB - Stereoselective effects of mianserin and ORG3770 on serotonin 5-HT3 receptors in mouse neuroblastoma N1E-115 cells have been investigated in radioligand binding and in whole-cell voltage clamp experiments. The specific binding of [3H]GR65630 to 5-HT3 recognition sites in N1E-115 cell homogenates is reduced by mianserin and ORG3770 and their enantiomers. The pKi values of the more potent (R)enantiomers of mianserin and ORG3770 are 8.44 and 8.62, respectively. The (R)enantiomers of mianserin and ORG3770 are 15 and 37 times more potent than their respective (S)enantiomers. The racemates are only 1.9 and 3.3 times less potent than the corresponding (R)enantiomers. In voltage clamp experiments the (R)enantiomers block the 5-hydroxytryptamine(5-HT)-induced ion current with pIC50 values of 8.52 for (R)mianserin and 8.26 for the (R)enantiomer of ORG3770. The (R)enantiomers of mianserin and ORG3770 are 24 and 145 times more potent in blocking the 5-HT-induced ion current than their respective (S)enantiomers. The racemates are 6 and 13 times less potent than the corresponding (R)enantiomers. In addition, the block of 5-HT-induced ion current by the (R)enantiomer of ORG3770 is partially reversed by a low concentration of its (S)enantiomer. The results indicate that the two enantiomers block the 5-HT3 receptor-mediated ion current in a mutually dependent manner. PMID- 7984290 TI - Zatosetron, a 5-HT3 receptor antagonist in a multicenter trial for acute migraine. AB - Zatosetron (13 mg or 0.19 mg/kg), a potent and selective 5-HT3 receptor antagonist was studied with a 30 min infusion in a crossover double-blind placebo controlled trial for acute migraine therapy. Groups receiving zatosetron and placebo were demographically similar and zatosetron was well-tolerated in all patients with no clinically significant adverse effects. Migraine severity was reduced in both the placebo and zatosetron groups with no statistically significant differences between zatosetron and placebo. Likewise, no statistically significant differences between placebo and zatosetron treatment groups were identified with regard to migraine duration, overall migraine severity or the relief medication required. Although several limitations of this study exist, these data documenting a lack of benefit of intravenously administered zatosetron in alleviating the acute pain of migraine add to the list of 5-HT3 receptor antagonists that have failed to support efficacy of this therapeutic modality in the acute treatment of migraine. PMID- 7984291 TI - (R) and (S) RS 56532: mixed 5-HT3 and 5-HT4 receptor ligands with opposing enantiomeric selectivity. AB - The pharmacological properties of the (R) and (S) enantiomers of RS 56532 have been studied in vitro and in vivo. In radioligand binding studies at 5-HT4 receptors in guinea-pig striatum, (S) RS 56532 exhibited a higher affinity than (R) RS 56532 (-log Ki = 7.6 and 6.5, respectively). (S) RS 56532 acted as a potent agonist at 5-HT4 receptors mediating relaxation of rat oesophageal muscularis mucosae (-log EC50 = 7.9) while (R) RS 56532 acted as a weaker agonist at this receptor (-log EC50 < 6.0). These data suggest that at 5-HT4 receptors, the enantiomeric selectivity of RS 56532 was (S) > (R). In binding studies at 5 HT3 receptors in rat cortex, (R) RS 56532, conversely, exhibited a higher affinity than (R) RS 56532 (-log Ki = 9.1 and 8.0, respectively). At 5-HT3 receptors in guinea-pig isolated ileum, (R) RS 56532 exhibited an affinity (-log KB) of 7.9, whereas (S) RS 56532 (1 nM-1 microM) was inactive. No agonism was observed at ileal 5-HT3 receptors with either enantiomers. These data suggest that at 5-HT3 receptors in rat and guinea-pig, both enantiomers acted as antagonists, with (R) > (S) RS 56532. At the non-5-HT3, high affinity '(R) zacopride' site, (R) RS 56532 exhibited a higher affinity than (S) RS 56532 (-log Ki = 6.1 and 4.9). This site was insensitive to potent 5-HT3 antagonists such as (R) YM 060 or ondansetron. However, it was recognized with relatively high affinity (-log Ki = 7.5) by the (R), but not (S) enantiomer, of RS 42358 (-log Ki = 4.7). Since (S) RS 42358 is a high affinity 5-HT3 receptor antagonist, these data further highlight the dissimilarity between the 5-HT3 receptor and the '(R) zacopride' site. The '(R) zacopride' site also appeared to be pharmacologically distinct from the 5-HT4 receptor, since 5-HT4 ligands such as renzapride, SDZ 205,557 or RS 23597-190 exhibited low affinities. The enantiomeric selectivity of (R) and (S) RS 56532 in vivo was consistent with findings in vitro. At 5-HT4 receptors mediating tachycardia in the pig, 5-HT induced a dose-dependent tachycardia (ED50 = 3 micrograms kg-1, i.v.; maximum response = 90-100 beats min 1). (S) RS 56532 increased heart rate by 88 min-1 with a potency of (ED50) of 3 micrograms kg-1, i.v.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 7984292 TI - Regional distribution and ontogeny of 5-HT4 binding sites in rodent brain. AB - We have investigated the regional distribution of 5-hydroxytryptamine4 (5-HT4) receptor binding sites in the adult guinea pig, rat and mouse brain using the specific 5-HT4 antagonist [3H]GR113808 as a radioligand. The developmental changes in the expression of these binding sites were also investigated quantitatively in the rat brain (gestational days 16 and 19; postnatal days 1, 3, 7, 9, 12 and 21). In order to compare previously obtained data on primary cultures, semi-quantitative analysis was also performed during mouse brain ontogeny (postnatal days 1, 7 and 11). The main finding of this study is that 5 HT4 receptors have comparable, wide and heterogeneous distributions in the adult brain of the species investigated, with densities reaching adult levels between the second and third postnatal week in most regions of the rat and mouse brain. In contrast, a progressive loss of 5-HT4 binding sites is observed in the pons, whereas a transient peak of receptor expression is seen during the second postnatal week in the globus pallidus and substantia nigra pars lateralis. The developmental pattern of 5-HT4 receptor distribution suggests, except in latter regions, that these receptors probably exert a minor role in developmental processes. In the adult, high densities of [3H]GR113808 binding sites are present in various regions belonging to limbic system (islands of Calleja, olfactory tubercle, fundus striati, ventral pallidum, septal region, hippocampus, amygdala), or known to be components of different pathways, such as the hippocampo-habenulo-interpeduncular and the striato-nigro-tectal pathways. While the regional distributions of [3H]GR113808 binding sites were identical in the mouse and rat, some differences were observed in the guinea-pig, in particular in the globus pallidus, substantia nigra and interpeduncular nucleus. The expression of 5-HT4 receptors in limbic areas is highly suggestive of a role for these receptors in emotional processes, whereas their expression in the striato-nigral tectal pathway might be indicative of a role in the control of visuo-motor activity. PMID- 7984293 TI - Identification of serotonin 5-HT4 recognition sites in the porcine caudate nucleus by radioligand binding. AB - Specific binding for the serotonin 5-HT4 receptor (5-HT4R) radioligand [3H]GR 113808 was identified in pig caudate nucleus and characterized by serotonin subtype selective drugs. Binding was inhibited by serotonin and by synthetic indoles, benzamides and benzimidazolones known to characterize the 5-HT4R in functional tests. Rank order of potency of 5-HT4R antagonists was: GR 125487 (Ki, 0.19 nM) > GR 113808 >> SC 53606 > SDZ 205,557 > RS 235971/190 > DAU 6285 > tropisetron > DAU 6215. GR 125487 and GR 113808 were highly selective with respect to the 5-HT3 receptor (5-HT3R). Rank order of potency of 5-HT4R agonists was: SC 53116 (Ki, 21 nM) > BIMU 1 > cisapride > BIMU 8 > serotonin > renzapride > S-zacopride > metoclopramide > R-zacopride > 5-methoxytryptamine >> 5 carboxamidotryptamine. BIMU 8, renzapride, metoclopramide and the zacopride enantiomers gave shallow competition curves. The agonists were substantially less selective than the antagonists with respect to the 5-HT3R. With only two exceptions, SCH 23390 and metergoline, which bound with sub-microM affinity to the 5-HT4R, binding was not inhibited by compounds selective for other G-protein coupled or channel-gated receptors. Highly significant correlations in affinities of compounds for 5-HT4R in caudata of pigs, guinea pigs and humans were found suggesting no difference among mammalian species. PMID- 7984294 TI - 5-HT1A and 5-HT4 receptor colocalization on hippocampal pyramidal cells. AB - The mixed inhibitory and excitatory effects of 5-HT on hippocampal pyramidal cells were studied on hippocampal slices perfused with a low-Ca2+/high Mg2+ solution that blocked synaptic activity and induced spontaneous pyramidal cell discharge. Extracellular recordings of the spontaneous discharge revealed that, in 65% of the cells, 5-HT (0.5-10 microM) initially inhibited and then, upon washout, facilitated spontaneous discharge. Sometimes the off-stimulation persisted for the duration of the experiment. In 17% of the cells the response to 5-HT was only stimulatory, and in 15% the response was exclusively inhibitory. The 5-HT1 agonists, 8-hydroxy-dipropylamino-tetraline, and 5 carboxamidotryptamine produced inhibition with no excitatory responses upon washout. The inhibition was blocked by spiroxatrine indicating it was mediated by 5-HT1A receptors. The 5-HT3 agonist, 2-methyl 5-HT, had no effect, and the 5-HT2 antagonist, ketanserin, did not alter the excitatory responses to 5-HT. This indicates the excitatory response is not mediated by 5-HT2 or 3 receptors. Cisapride, a 5-HT4 agonist increased pyramidal cell discharge. The 5-HT3 & 4 antagonist, ICS 205-930 antagonized the excitatory responses to 5-HT, alpha methyl 5-HT, and cisapride, indicating the excitatory response is mediated, in part, by 5-HT4 receptors. The phosphodiesterase inhibitor, isobutyl-methyl xanthine, stimulated pyramidal cell discharge and potentiated the response to cisapride. This further suggests 5-HT4 receptor involvement since these receptors are positively coupled to adenylyl cyclase. PMID- 7984295 TI - Tryptophan depletion in normal volunteers produces selective impairments in learning and memory. AB - The amino-acid L-tryptophan is essential in the synthesis of brain serotonin, and its depletion can lead to a widespread reduction in central serotonergic activity. A placebo-controlled cross-over within-subjects design (n = 12) examined the effects of tryptophan depletion on human cognitive performance. A low-tryptophan (low-TRP) drink successfully reduced the levels of plasma and total free tryptophan. Computerized tests of memory, learning and executive function revealed selective and non-sedative impairments on cognitive performance following the active drink. Specifically, low-TRP impaired learning as seen in tests of visual discrimination and paired associates. Furthermore, low-TRP lengthened thinking times during the Tower of London planning task, but only in subjects already familiar with the task, suggesting a retrieval deficit. No evidence was found for an effect of the low-TRP drink on measures sensitive to frontal lobe dysfunction, supporting instead a specific role for the serotonergic system in the processes of memory and learning not directly implicated in frontal lobe function. PMID- 7984296 TI - The incidence of overuse injuries in military recruits during basic military training. AB - A study was undertaken to document the incidence of overuse injuries sustained during basic military training. The injuries in military recruits (N = 1,261) undergoing basic training were documented prospectively over a 9-week period. Injury incidence was expressed as percentage of all recruits injured, weekly incidence (injuries/1,000 recruits/week), and injuries/1,000 training hours. The incidence of six common specific overuse injuries was also recorded. The overall incidence of injuries over the 9-week period was 31.9% (acute, 13.6%; overuse, 86.4%), or 1.8/1,000 training hours. The highest incidence of injuries was recorded in weeks 1 to 3 and week 9 of training, which were weeks characterized by marching ( > 77% of the training time). The highest incidence (injuries/1,000 training hours) of specific overuse injuries were tibial bone stress reaction (0.33), patellofemoral pain (0.22), and the iliotibial band friction syndrome (0.08). The incidence of stress fractures over the 9-week period was 1.2% (0.07/1,000 training hours). Injuries to the knee, lower leg, and ankle accounted for more than 80% of all injuries. A total of 3.6% of training days were lost during this period, mainly due to bone stress injuries. In order to reduce injuries during basic military training, attention must be directed towards (1) modifying the type of training and (2) prevention of bone stress injuries. PMID- 7984297 TI - Treatment of third molars in Finnish conscripts. AB - Third molar-related dental treatment was investigated in 14,500 Finnish 20-year old male conscripts during their 8 to 11 months' time of service. One thousand five hundred ten conscripts needed dental treatment because of third molars. Four hundred thirty-two third molars were filled, whereas 1,881 third molars were extracted. Forty percent of the removed 1,072 mandibular teeth required tooth sectioning and/or buccal bone relief. Forty-eight percent of the patients lost military serving time (at mean 4.2 days per case), most often because of postoperative discomfort. The number of complications was low. PMID- 7984298 TI - Laparoscopically assisted vaginal hysterectomy in an Army medical center. AB - Over the past 5 years, laparoscopic assisted vaginal hysterectomy (LAVH) has progressed from an experimental procedure to an alternative operation when abdominal hysterectomy is indicated. During a 15-month period, 31 patients underwent LAVH at Tripler Army Medical Center for treatment of gynecologic conditions that traditionally required abdominal hysterectomy. The benefits of the procedure and the complications encountered during surgery are discussed. A comparison of our data with data presented in other reports in the literature is considered favorable. While the complication rate was 16%, there was no mortality or serious morbidity. With experience and proper training of gynecologic surgeons, LAVH is an alternative to abdominal hysterectomy in selected cases. PMID- 7984299 TI - Questioning vision readiness in the aviation community of the United States Air Force. AB - A study was conducted to determine the prevalence of substandard visual acuity in a representative sample of the aviation community. In addition, mobility readiness (ocular), ocular diseases, length of time since last visual examination, and adherence to ocular requirements per AFR 160-43 were assessed. Comprehensive eye examinations were performed in the Optometry Clinic on 68 randomly chosen members scheduled by the participating squadron. Of the 68 individuals, 51 (75%) had not had a professional eye examination in the last 2 years, 17 (25%) were not mobility ready, 15 (22%) had inadequate visual acuity per AFR 160-43, and 3 (4%) had ocular disease. The study suggests that comprehensive visual examinations be performed on a regularly scheduled basis by an optometrist or ophthalmologist to ensure that members see properly to perform assigned duties, that members have required optical materials to be deployment ready, and that members who develop ocular diseases be identified in a timely manner. PMID- 7984300 TI - Intensive care of severely wounded military and civilian casualties in Zadar, Croatia. AB - From August 1, 1991, to May 30, 1992, 148 severely wounded military and civilian casualties with the injury severity score of 3 to 5 were treated in the intensive care unit of the Zadar General Hospital. There were 138 male and 10 female patients; their mean age was 32 years. There were 64 wounded civilians and 84 wounded soldiers. The average evacuation time was 3 hours. Twelve (8%) severely wounded persons died. The cause of death was craniocerebral injury in 7 patients (58%) and hemorrhage in 4 patients (33%). Complications following shock-like acute renal failure, gastrointestinal bleeding, coagulopathy, and hepathopathy developed in 18 wounded persons (12%). PMID- 7984301 TI - Illness and injury among U.S. prisoners of war from Operation Desert Storm. AB - United States prisoners of war had to endure a variety of medical problems during Operations Desert Shield and Desert Storm. All but one of the prisoners suffered some form of injury or illness. Orthopedic injuries were most common. Hematologic, dermatologic, neurologic, and infectious disorders were also noted. Some injuries were combat-related and others were due to mistreatment during incarceration. The prisoners' condition upon repatriation reflected their limited access to appropriate medical care, sanitation, and nutritional support. PMID- 7984302 TI - U.S. Army Reserve optometry mobilization in support of Operations Desert Shield and Desert Storm. AB - Reserve participation contributed significantly to the successful optometric support of the U.S. Army in Operations Desert Shield and Desert Storm. This survey profiles the experiences of reserve optometry officers during these operations. Many doctors suffered personal and financial hardship, the latter being particularly common for those in private practice settings. Readiness may be impaired as many responses indicated that a considerable number plan to separate from the reserve in order to avoid future activation. PMID- 7984303 TI - Diarrheal disease aboard a U.S. Navy ship after a brief port visit to a high risk area. AB - In August 1988, a study was conducted to determine the etiology and risk factors associated with travelers' diarrhea among U.S. military personnel after a 5-day port visit to Alexandria, Egypt. Twenty-one percent of the 2,747 evaluated crew members of the USS John F. Kennedy reported an episode of acute diarrhea, which led to 155 sick-call visits and at least 110 lost man-days. The most common pathogen identified was enterotoxigenic Escherichia coli, and all isolated bacterial enteropathogens were sensitive to quinolone drugs. Independent risk factors for the development of diarrhea included: (1) consuming any meal ashore and specifically eating meats, desserts, or a buffet meal; and (2) a recent history of travelers' diarrhea. These data indicate that even brief port visits to developing countries pose a major threat to the health of U.S. shipboard personnel. PMID- 7984304 TI - The Exceptional Family Member Program: views of unit leaders. AB - This survey indicated that unit leaders perceived the Army Exceptional Family Member Program (EFMP) positively and considered the program beneficial to the Army, the soldiers, and their families. Furthermore, the unit leaders considered the EFMP soldiers to be well accepted in their units and their duty performance to be comparable to that of non-EFMP soldiers. PMID- 7984305 TI - Use of inpatient psychiatric services on a U.S. Army combat support post during Operations Desert Shield and Desert Storm: the stress of non-deployment. AB - We studied the utilization of inpatient psychiatric services during Operations Desert Shield and Desert Storm (the Persian Gulf War of 1990-1991) on a U.S. Army combat support post. Inpatient psychiatric admissions and dispositions for the post's catchment area were tallied before, during, and after Operations Desert Shield and Desert Storm. Subjects included active duty soldiers (deployed soldiers were not studied while they were away from the post), their families, and retirees. Overall, there was no increase in psychiatric hospitalizations for active duty soldiers, their family members, or retirees. However, coincident with the return of soldiers from Operations Desert Shield and Desert Storm, the psychiatric proportion of all hospitalizations increased in the subpopulation of soldiers not deployed who had served less than 1 year. These soldiers in training may be more susceptible to increased stress levels associated with the return of soldiers from war because of their inadequate group bonding. PMID- 7984306 TI - Comparisons of casualty presentation and admission rates during various combat operations. AB - Daily casualty rates were analyzed and compared for four ground operations: Okinawa, Korea, Vietnam, and the Falklands. Daily admission rates of wounded-in action (WIA) for combat troops ranged from 1.61 to 5.54 per 1,000 strength. The killed-in-action rates of combat troops ranged from 0.2 to 1.35. Support troop WIA admission rates ranged from 0.05 to 0.43 per 1,000 strength per day. Among wounded combat troops, the mean number of sick days before return to duty were 4.3 and 5.1 days for two different operations. PMID- 7984307 TI - Medical observations of malingering in Iraqi enemy prisoners of war during Operation Desert Storm. AB - The authors, who were at the Al Khanjar enemy prisoner of war (EPW) collection point along the Saudi Arabian-Kuwaiti frontier during Operation Desert Storm, furnish two accounts of malingering and deliberate, manipulative attempts at "conning the doctors" by Iraqi EPWs of the Republican Guard Corps. To some extent, malingering and conning of the doctors with faked illness or complaint expended time and other valuable resources that could have been directed toward EPW patient care and treatment with genuine medical bases. PMID- 7984308 TI - Changes in triiodothyronine mark severe pain syndrome: a case report. AB - Non-thyroidal illness is classically associated with a low total triiodothyronine (T3) level. Episodes of severe recurrent dental pain unassociated with fever or systemic infection in a patient was marked 2 to 3 weeks later by low T3 levels (56 ng/ml). Other thyroid and metabolic tests were normal. T3 levels returned to normal on resolution of pain. Recurrence of a transient, mild episode of pain was not associated with a low T3 2 weeks after its onset. We suggest that T3 levels may be markers for severe pain and suffering or disturbances responsible for pain and suffering in patients receiving analgesics. PMID- 7984309 TI - The use of synthetics in cranioplasty: a clinical review. AB - Materials used to repair cranial defects have evolved tremendously over the past several decades. Advances in metallurgy, the development of acrylics, and the advent of modern imaging and histologic techniques all have played a role in improving cranioplastic materials. Discussed here is a case report depicting the use of synthetics in cranioplasty, followed by a review of the historical development of these materials. PMID- 7984310 TI - Pseudolymphoma of the breast: case report and literature review. AB - Pseudolymphomas of the breast are extremely rare: the etiology of these lesions is unclear, but some believe they may represent a response to local injury. Although morphologically similar to malignant lymphomas, they are benign. Here we report a case of pseudolymphoma of the breast and present a review of the literature. PMID- 7984311 TI - Benign adenoma of the ampulla of Vater presenting as obstructive jaundice. AB - A case of benign villous adenoma of the ampulla of Vater is presented with a review of the literature. Diagnostic modalities and surgical approaches are discussed. PMID- 7984312 TI - [Expired ethane as a non-invasive marker of the course of experimental multiple organ dysfunction syndrome (MODS)]. AB - BACKGROUND AND WORK HYPOTHESIS: The mechanisms of organ damage in MODS are unclear. Given that lipid peroxidation induced by oxygen radicals may play a key role in organ damage, expired ethane, a marker of lipid peroxidation, could be correlated to the entity and evolution of experimental MODS. STUDY DESIGN AND METHODS: Forty wistar male rats (250 +/- 15 g body weight) were intraperitoneally injected with 10 ml of Zymosan mineral oil suspension (2.5%) to provoke MODS. Survival and symptoms were noted daily. On the 2nd, 7th and 14th day the animals underwent thorax CT scanning. CT images were processed to evaluate the relative density of lung parenchima. Expired ethane was measured using mass spectrometer and percentual changes were noted. Relative organ weight (liver and lung) were measured in 2nd, 7th and 14th day. STATISTICAL ANALYSIS: Pearson's linear correlation. RESULTS: The results show that maximal lung damage took place at the same moments as ethane concentrations peaked. A strict correlation (r = 0.93; p < 0.0001) was found between lung density and expired ethane. Strict correlation was found between organ weight, symptoms, survival and ethane production. CONCLUSIONS: Lipid peroxidation, as expressed by ethane production, might be an important cause of organ damage in MODS. PMID- 7984313 TI - [Hemodynamic changes in orthotopic transplantation of the liver]. AB - OBJECTIVE: To evaluate the hemodynamic changes during orthotopic liver transplantation (OLT). DESIGN: Retrospective analysis of the hemodynamic data during OLT. SETTING: National Cancer Hospital. PATIENTS: Thirty-two patients with hepatic neoplasia and various degrees of cyrrhosis classified according to Child Pugh. INTERVENTIONS: Orthotopic liver transplantation. MEASUREMENTS AND MAIN RESULTS: For each of the six phases of the operation a complete hemodynamic profile was reported as general mean and as mean of each Child class. The catecholamins given were also reported. At baseline the Child C showed a cardiac index (CI) and heart rate higher than others. At the end of first phase the blood pressure (BP) of the Child C lowered more than the others'. The anhepatic phase was stable. At reperfusion CI increased, the systemic resistances and BP decreased in all the classes. The Child C needed more catecholamins at this time. In the last profile all tended to return to baseline values. CONCLUSIONS: The baseline hemodynamic was the more hyperdynamic the more sever was the cyrrhosis. The Child C, despite a meticolous fluid therapy, were prone to hypotension in response to even minimal decreases of filling pressures. At reperfusion an hemodynamic disturbance featured by systemic vasodilation occurred. It was more severe in the hyperdynamic patients and it was time limited. The causes of this disturbances have not yet been fully elucidated. PMID- 7984314 TI - [Anesthesia with isoflurane in air and with isoflurane and nitrous oxide]. AB - BACKGROUND: The aim of this study is to control the depth, the quality of recovery of total inhalation isoflurane anesthesia with or without nitrous oxide. DESIGN: Controlled comparative study was carried out on 51 patients, aged 40-54 yr, ASA 1, undergoing saphenectomy, in an University Clinic. METHODS: Induction: thiopental (3.5 mg kg), atracurium (0.6 mg kg) i.v. Patients were randomly assigned to: group 1 (26 patients), 5% isoflurane in air, by mask; group 2 (25 patients), 3% isoflurane and 60% N2O, by mask. Maintenance: group 1, 2% isoflurane in air; group 2, 1.2% isoflurane and 60% N2O. During anesthesia, consciousness and analgesia level were monitored by EEG Compressed Spectral Array, and clinical signs of pain by Evans' test; arousal time evaluation by "Time to correct response test". The subjective impressions, eventual dreams and recalls were collected using a standard set of questions one hour after the end of anesthesia and 24 hours later. One hour before anesthesia and two hours after the end of surgical procedures, a psychomotor performance recovery evaluation was performed using Zazzo's "deux barrages" test. DATA ANALYSIS: Student's "t" test. RESULTS: Adequate anesthetic depth was documented in all patients. Recovery time was statistically longer in isoflurane group (group 1 16.7 sd 2.2 minutes vs 10.3 sd 1.9 minutes group 2, p < 0.01). No patient reported recalls relative to anesthetic period. Two hours after recovery no significant differences in psychomotor performance tests were recorded. CONCLUSIONS: Isoflurane anesthesia in air, in adequate concentrations, provides a sufficient level of analgesia, hypnosis, amnesia, without clinical side effects. PMID- 7984315 TI - [Hemodynamic and metabolic effects of noradrenaline infusion in a case of hyperdynamic septic shock]. AB - AIM: To evaluate the effect of noradrenaline infusion in a case of hyperdynamic septic shock refractory to volume loading, dopamine and dobutamine, on hemodynamic parameters, oxygen transport, lactate and pyruvate levels. DESIGN: Description of a clinical case. SETTING: Postsurgical Intensive Care Unit in a University Hospital. PATIENT: A 48-year-old woman with symptoms of peritonitis due to Enterobacter Agglomerans and refractory hyperdynamic septic shock. INTERVENTIONS: Administration of noradrenaline in doses ranging from 0.03 to 0.14 micrograms/kg/min. MEASUREMENTS AND RESULTS: Before and after noradrenaline infusion the following were evaluated: hemodynamic (parameters) and oxygen transport acid-base status, arterial blood levels of lactate and pyruvate, and lactate/pyruvate ratio. During the administration of noradrenaline an increase was observed over time in oxygen consumption (from 110 +/- 16 to 164 +/- 19 mL/min/m2; p < 0.01), peripheral vascular resistance (from 509 +/- 95 to 1172 +/- 384 dynes.sec.cm-5, p < 0.01) and the oxygen extraction index (from 12.9 +/- 2.1 to 21.2 +/- 2.9%, p < 0.01), together with reduced lactate (from 24.4 +/- 1.5 to 4.9 +/- 5.1 mmol/L) and pyruvate levels (from 945 +/- 62 to 357 +/- 174 mumol/L; p < 0.01) and a reduced lactate/pyruvate ratio (from 26.2 +/- 1.2 to 11.8 +/- 5.9, p < 0.01). No significant increases were found in cardiac output and oxygen delivery. CONCLUSIONS: In the case observed here the infusion of noradrenaline induced an increase in oxygen consumption and the oxygen extraction index associated with a reduction in the lactate/pyruvate ratio and the normalisation of the acid-base status. These changes were not associated with an increase in oxygen which remained delivery > or = 600 mL/min/m2. PMID- 7984316 TI - [Multiple endocrine insufficiency associated with severe pregnancy jaundice. Description of a case and review of the literature]. AB - The case of a patient with postpartum pituitary failure associated with primitive adrenal failure, jaundice and sepsis is described. Radiologic findings, which initially suggested a pituitary necrosis, were normal two months after the admission. Diagnostic and therapeutic approaches are reviewed and discussed. PMID- 7984317 TI - [Multiple organ failure in pre-term pregnancy: gestosis and/or typhoid fever?]. AB - The authors describe a clinical case of Multiple Organ Failure (MOF). Such a pathology was reported, at admission in ICU, in a young woman aged 26 who was in the 30th week of amenorrhoea, formerly hospitalized in Obstetrics, where she had had a Caesarean section because of the met of eclamptic crisis, after a pregnancy substantially normal. At the moment of her admission to the ICU the examination highlighted the sense organ obnubilated, the breath dyspnoic, a systolic and diastolic hypotension and a tachycardia of medium seriousness. From laboratory examinations it was possible to maintain that there was a serious anemia with white cells raised, a coagulative imbalance and above all a serious alteration of hepatic and pancreatic function. The creatininemia had increased a bit, a clear contraction of diuresis was present and a considerable metabolic acidosis had become intelled. Therefore the patient was affected by multiple organ failure. In successive days it was possible to execute an EEG that proved substantially normal, then a Computer Tomography to abdomen showed the presence of vast areas of hepatic necrosis, ascitic hemorrhagic fluid and a volume increased pancreas. Hepatitis markers proved negative, while a positive response was achieved for a typhoid infection (this result was reconfirmed many times later.) Modifying the antibiotic therapy (substituting full dose ampicillin to the cephalosporin) the clinical case was solved. Moreover, also thanks to a very good answer to antibiotic therapy, it was possible to confirm the diagnosis of typhoid fever, not gestosis. PMID- 7984318 TI - [Bellhouse laryngoscope (Belscope). Technical notes and considerations]. PMID- 7984319 TI - [Helicopter assistance in Sicily. Peculiar aspects of a 3-year experience]. AB - OBJECTIVE: To report our experience concerning the first aid effected by helicopter both on scene (primary rescue) and interhospital transport of already treated patients requiring a highest level of diagnosis and treatment (secondary rescue), and the peculiar aspect appeared from the analysis of the obtained results, that is the predominance of the secondary rescue on the primary one. DESIGN: Retrospective evaluation of the interventions effected from August 1990 to February 1993. SETTING: Critical care units of a University teaching Hospital. MAIN RESULTS: 2669 interventions were effected: 2082 were secondary rescues (78%) and 587 primary rescue (22%). The patients actually transported by helicopter were 2419 (M = 1702; F = 717). The leading cause of non effected interventions was the deficiency of illuminated helicopter landing area; for the primary rescue, the main cause was the distance from the scene and the transport with land vehicles. The most frequent admission were for intensive care unit, neurosurgery, cardiac-surgery and neonatology, in only three towns. Indeed, the failing of Specialized Units involves the use of helicopter in interhospital transport for long periods, and this can remove time from primary rescue. CONCLUSION: As mentioned above, the peculiar aspect of our experience is the predominance of the secondary rescue on the primary one. It can be attributed particularly to the geographic and orographical characteristics of our region, together with the organization deficiencies in the field of emergency medical services. PMID- 7984320 TI - [Abuse of Student's t]. PMID- 7984321 TI - [Shoulder dystocia: some guidelines for prevention and treatment]. PMID- 7984322 TI - [Current conservative surgery in cervical intraepithelial neoplasia]. AB - 5 years (1989-1993) experience of cervical conization including 57 cases, has been reviewed. The mean follow-up was 33 (6-60) months. Mean age was 34.6 (range 21-57) years. Mean height and diameter of the cones were 2.5 +/- 0.3 cm and 1.5 +/- 0.4 cm, respectively. In 55 cases there were free margins of the cones. Cytological diagnosis was CIN I for 8 patients, CIN II for 21 patients, CIN III for 22 patients, CIN+HPV for 6 patients. In 40 of the 57 patients suspected of having a cervical intraepithelial neoplasia on cytology and on colposcopy, the histology was confirmative. Bleeding (the most common pre and postoperative complication) was observed in 6 cases (11.7%). In three patients a new conization was necessary and in the other two patients hysterectomy was necessary. No significant differences were noted in the pregnancy outcome following either treatment in five patients. PMID- 7984323 TI - [Discrepancy between histopathological diagnosis based on guided biopsy and cone biopsy of the cervix uteri: analysis of 346 cases of laser conization]. AB - The conservative management of cervical intraepithelial neoplasia (CIN) essentially depended on the introduction and improvement of colposcopy. This technique, allowing to locate the lesion, to estimate its extension and to perform multiple punch biopsies, becomes discriminant in therapeutic choice. Whether colposcopy reveals endocervical involvement or abnormal transformation zone (ANTZ) may be only partially explored, excisional conization should be preferred to ablative therapy since the former advantageously can verify histopathologic diagnosis, confirm completely excision of lesion and rule out invasive carcinoma. The literature shows that cases of invasive lesions can be underestimated and therefore inadequately treated by ablative therapy, emphasizing colposcopy and punch biopsy limitations about suspect and diagnosis of microinvasion. We analyzed data concerning preliminary diagnostic investigations and results of 346 CO2 laser excisional conizations performed between 1984 and 1993. Histopathologic diagnosis on punch biopsy, performed in 111 cases of ANTZ1 and in 235 cases of ANTZ2, shows an agreement with cone biopsy in 30.8% of the cases of CIN1, of 40.9% in cases of CIN2 and of 66.3% in cases of CIN3. Whereas the lesion is overestimated in 30.6% of cases, in which it is likely that punch biopsy has removed the epicenter of the lesion or the lesion in toto, we had an underestimation in 15% of cases, particularly in 4 cases of CIN2, in 38 cases of CIN3 and in all microinvasive processes. The rate of invasive lesions previously ignored and detected only by histopathologic diagnosis on cone biopsy is 2.9%. In only one of these cases colposcopy, even if attributing to each of these the higher grading, shows the suspicion of invasion, whereas the detection of invasive processes is missed in every case by punch biopsy.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7984324 TI - [Vulvo-cervico-vaginal inflammatory pathologies in childhood and adolescence. Our experience]. AB - One hundred and twenty-seven pediatric and adolescent patients suffering from vulvo-vaginitis underwent clinical and instrumental tests. The results of bacterioscopic and cultural test were negative in 39 (31.7%) patients due to the probable intervention of local hormonal, allergic and/or irritative factors. The tests used by the authors revealed phlogosis in 88 patients (68.3%) which was aspecific in 58 cases (65.9%) and specific in 30 (34.1%). While aspecific phlogosis were basically caused by germs of intestinal origin, typical of childhood and the prepuberal period, mycetes, gardnerella vaginalis, protozoa and chlamydia trachomatis were identified as the causes, in order of importance, of specific phlogosis, the exclusive hallmarks of adolescence. PMID- 7984325 TI - [Varicocele and infertility: clinical framework and therapeutic approach]. AB - A diagnostic-therapeutic protocol which can be used in patients affected with varicocele, in order to obtain a complete clinical study of them and try to improve functional results of therapy, is described. The aims of this protocol are: precise diagnosis of venous refluxes, examination of testicular functionality, detection of possible associated pathologies which can cause infertility, establishment of correct indication to hormonal postoperative therapy. The rapid surgical correction of venous stasis, the treatment of prostatic phlogosis, often concomitant, and, in selected patients, the use of hormonal therapy, can improve functional results in the treatment of this pathology. PMID- 7984326 TI - [A new surgical technique to reduce genital-urinary prolapse]. AB - The authors describe a new surgical technique to reduce the prolapse of genitals and urinary organs. In retrospect, we studied 36 women--between the ages of 59 and 85--who had been hospitalized from 1988 through 1990 at the Ospedale di S. Anna of Rome and from 1991 through May 1994 at the Ospedale Sandro Pertini of Rome. Twenty-eight out of 36 patients presented a III prolapse of the uterus with cystorectocele; 4 patients had a prolapse of the cupola vaginae after hysterectomy; 4 patients presented a prolapse of the residual stump after sub total hysterectomy. In addition, 8 out of 36 patients presented a stress incontinence. The technique described adopts a special nylon lace to fix prolapsed organs to the fascia musculorum rectorum abdominis. Its ease and brief execution time, together with the complete lack of relapse, have convinced the authors to promote the diffusion of this technique, which allows relief from these extremely distressing complaints often not fully cured with traditional techniques. PMID- 7984327 TI - [Clinical and instrumental evaluation after Burch's colposuspension in patients with stress urinary incontinence]. AB - The authors performed a retrospective study of 29 patients undergoing Burch's anterior colposuspension to treat stress incontinence. Patients were aged between 32 and 71 years old and before surgery presented a urodynamic picture with low mictional pressure, normal filling and Max P of lower closing at 40 mm. Follow-up monitoring ranged from a minimum of 6 months to a maximum of 5 years (mean length 33 months) and was carried out using a urodynamic examination and transvaginal scan to evaluate the distance of the bladder neck from the posterior face of the pubic symphysis. Seventeen women (65.5%) were fully cured after surgery, whereas 27% improved. In "dry" patients the urodynamic examination showed increased significantly of the functional length of the urethra and the transvaginal scan showed that mean values of the distance between bladder neck and pubic symphysis were lover than those in those patients who still presented symptoms. The authors also used ultrasonography to evaluate the efficacy of the latter in the study of urinary incontinence. As reported in other studies, they affirm that intracavitary ultrasonography using a linea probe is equivalent to radiography using cystography with metallic repere, making the examination less invasive and easily repeatable; in addition, it is also important for studying the dynamics of the pelvic floor to establish effective rehabilitative treatment. PMID- 7984328 TI - [Beta interferon in clinical practice]. AB - Intramuscular interferon beta determines a positive therapeutic effect on the moderate dysplasia of the when associated with infection by HPV. The therapeutic effect is expressed mainly by progressive viral regression. Also our results show a satisfactory answer to the treatment with intramuscular interferon beta: in fact, the patients we treated had a positive reaction in terms of regression of the infection distinctly superior to what is the spontaneous regression of the infection itself. PMID- 7984329 TI - [Use of alpha interferon in microcondylomatosis of the female genitalia]. AB - The Authors report the results of their research into the use of the alpha interferon in the microcondylomatosis of the female genital apparatus. The therapy was successful in 18% of cases. Considering oncological risk connected with the permanency of the HPV in the uterine portio, the Authors consider they must continue the study on new diagnostic and therapeutic protocols. PMID- 7984330 TI - [Use of fibrin glue in premature rupture of membranes]. AB - Following a careful review of the international literature and the rationale underlying the use of fibrin cement in obstetrics, the authors describe the application of this technique in a case of premature rupture of the membranes at week 21 of pregnancy which subsequently concluded positively with spontaneous birth at week. They also underline the need to study and evaluate carefully all contraindications to the use of fibrin cement. PMID- 7984331 TI - [Treatment in the event of antibiotic prophylaxis failure in gynecologic surgery. A retrospective study of 20 cases]. AB - A retrospective study was performed of the type of treatment used in 20 patients undergoing gynecological surgery in whom antibiotic prophylaxis with Mezlocillin (2 g i.v.) had failed. Patients were subdivided into three groups: A) Initial therapy with Mezlocillin (8 patients, 2 g/die i.m.) or Cefotetan (2 patients, 2 g/die i.m.) and subsequent addition of Gentamicin (8 patients, 240 mg/die i.m.) or Tobramycin (2 patients, 200 mg/die i.m.) and subsequently Metronidazole (7 patients, 1.5 g/die per os). B) Therapy with Imipenem/Cilastatin (6 patients, 1.5 g/die i.m.). C) Therapy with Imipenem/Cilastatin (4 patients, 1.5 g/die i.m.) after a variety of antibiotics: Cotrimoxazole (Trimethoprim 160 mg/die and sulphamethoxazole 800 mg/die per os), Pefloxacin (800 mg/die per os), Cefotetan (2 g/die i.m.) and Mezlocillin (2 g/die i.m.). Time taken to lower temperature was shorter in Group B (3.5 days) compared to Group A (6.8 days) and Group C (10 days). Postoperative hospital stay was also shorter in Group B (9 days) compared to Group C (16.5 days) and Group A (11.1 days). The immediate administration of an antibiotic active against Gram+ and Gram- germs, aerobes and anaerobes is therefore useful in the event of failure of antibiotic prophylaxis, rather than the use in succession of associations of antibiotics with a limited spectrum. PMID- 7984332 TI - [The IUD and uterine perforation]. AB - The intrauterine device (IUD) is an effective and relatively safe contraceptive. Approximately 15% of women of child-bearing age in Italy use the IUD. The major health risks associated with IUD use are perforation of the uterus, pregnancy (both intrauterine and ectopic), and pelvic inflammatory disease. Perforation of the uterus by an IUD is a serious complication and this is possible both during the insertion and later. Perforation of the uterus is rare, but potentially fatal. The incidence is of 0.12-0.68/1000 insertion. Although some patients have signs and symptoms suggestive of perforation (pain or bleeding), many are apparently asymptomatic at the time the diagnosis of perforation is made. Perforation is often suspected or diagnosed when the IUD string is no longer visible at the external os. A patient who has sustained a perforation is not protected against pregnancy. Numerous factors affect perforation: the type of IUD, the uterine size and position, timing of the insertion in relation to the last delivery or abortion and the experience of the clinical. Serious consequences have been described, such as severe damage to the viscera (i.e. bowel, kidney) and/or peritonitis. The diagnosis is clinical, ultrasonic, radiological and coelioscopic. Coelioscopic diagnosis makes it possible to choose the method of treatment. In experienced hands, this method is rapid, the hospitalization required short and the sequelae simple. PMID- 7984333 TI - [Heterologous mesodermal adenosarcoma of the endocervix. Description of a clinical case]. AB - We describe a case of an endocervical heterologous mesodermal adenosarcoma, found in a 43 year old woman. Among mesodermal neoplasms, various histological types are distinguished: the carcinosarcoma, the embryonal rhabdomyosarcoma or botryoid sarcoma, and the adenosarcoma; the last is formed by a benign epithelial component and by a malignant stromal component, that may contain heterologous tissues, such as cartilage, skeletal muscle, etc. Adenosarcoma is a tumor of the uterine corpus and seems to be most common among menopausal women. A primitive adenosarcoma of the uterine cervix is very rare; in fact the overall percentage of the uterine cervical sarcoma is 0.2-0.4%. The patient, age 43 years, with regular menstrual bleeding came to an outpatient clinic referring a post coital metrorrhagia. After a control examination, a polyp from the uterine cervix was removed; the histopathologic diagnosis was: fibroangioadenomatous polyp of the isthmus with cartilaginous metaplastic areas. Two months later, the patient was referred to our clinic and another cervical polyp was removed. The histological diagnosis was adenosarcoma with chondrosarcomatous heterologous mesodermal component. Then the patient was operated and the postoperative histological examination confirmed the preoperative diagnosis. A literature review about the uterine adenosarcoma etiopathogenesis is reported, and a suitable diagnostic iter, is discussed. PMID- 7984334 TI - [Diagnosis and treatment of intrauterine pregnancy associated with tubal pregnancy. Description of a clinical case]. AB - Description of a clinical case. In the last decade we have witnessed an increase in both ectopic and twin pregnancies. These events have various causes, such as PID, tubal plastic surgery, the use of agents for the induction of ovulation and many others. The number of intra- and extra-associated pregnancies (phenomenon that was considered quite rare in the past) has also been increasing. A medical case that has come under our observation is being discussed. A woman patient arrived in our ward with typical symptomatology of threatened abortion at the 8th week of amenorrhea. The echographic test showed an intra-uterine pregnancy in regular progress associated with right latero uterine tumefaction. The Douglas cavum was full of liquid of probable hematic nature. The promptly performed laparoscopy confirmed the suspicion of intra and extra uterine associated pregnancy. The consequent right adnexectomy through laparotomy led to the solution of the case. PMID- 7984335 TI - Gustatory cortex of primates: anatomy and physiology. AB - Clinical and physiological studies of patients with ageusia or gustatory hallucination suggest that the primary gustatory area (area G) lies at the anterior insula or at the base of the central sulcus. However, physiological and anatomical studies in subhuman primates, e.g. squirrel monkeys or macaque monkeys, locate area G at the buried frontal operculum (Fop) and dorsal insula. The presence of secondary or higher gustatory areas are claimed because taste neurons are found in the precentral opercular area (PrCO) or orbitofrontal cortex in alert monkeys. Part of the anterior insula is suggested to subserve the interface between area G and the amygdala. Many physiological studies have been conducted lacking knowledge of the histological boundaries of the primary and secondary gustatory areas. Some difference has been found in the physiological properties of taste neurons in the primary and secondary gustatory areas: the primary gustatory area contains various categories of taste neurons, whereas most of the taste neurons in the secondary gustatory areas (e.g., PrCO, area 1-2) are specifically sensitive to one of the four basic tastes, and taste neurons in the orbitofrontal opercular area (OFO), another secondary gustatory area, show sensory-specific hunger as well. PMID- 7984336 TI - Cajal-Retzius neurons identified by GABA immunohistochemistry in layer I of the rat cerebral cortex. AB - By means of immunohistochemistry using anti-gamma-aminobutyric acid (GABA) antibodies, characteristic neurons of pyriform, bipolar or pleomorphic shapes, regarded as the Cajal-Retzius (CR) neurons, were clearly demonstrated in layer I of the rat cerebral cortex at the various experimental periods. On embryonic day 15, ovoid neurons only in the marginal zone indicated immunoreactivity for GABA. They gradually extended thick processes often in parallel with the pial surface and formed a dense GABA fiber network in immature layer I during the early postnatal periods. Some GABA neurons seemed to migrate into the underlying layers to settle as nonpyramidal cells. With the expansion of brain volume, GABA neurons relatively diminished and decreased in number. Nevertheless, a small number of GABA neurons did exist as essential CR neurons in layer I even in the adult rats aged 9 months. PMID- 7984337 TI - Onset and stabilization of NMDA receptor-dependent hippocampal long-term potentiation. AB - This article discusses recent data concerning the temporal development of N methyl-D-aspartate (NMDA) receptor-dependent potentiation in the hippocampus. It argues against a mechanistic subdivision of NMDA receptor-dependent potentiation into an early short-term potentiation (STP) and a slowly developing long-term potentiation (LTP). Thus, the article proposes that LTP starts a few seconds after the induction event, that it is fully developed within a minute, and that its subsequent stabilization is controlled by the degree of NMDA receptor activation, and associated increase of calcium concentration in the spine, during the induction event. It is suggested that most biochemical interventions that have been reported to interfere with the LTP process, for example application of protein kinase inhibitors, might have acted through an impairment of the induction mechanism rather than through an impairment of specific stabilization or maintenance mechanisms. PMID- 7984338 TI - Comparison of brain dopamine depletion induced by low-dose 1-methyl-4-phenyl 1,2,3,6-tetrahydropyridine (MPTP) in young and aged rats. AB - Effects of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) on dopamine levels in the striatum (ST), substantia nigra (SN), olfactory tubercle (OT), ventral tegmental area (VTA) and nucleus accumbens (NA) were studied in young (1 month) and old (21 months) male Long-Evans rats. Following repeated treatment with MPTP at low dose (3 mg/kg i.p. daily for 8 days) both young and old rats showed a marked depletion of dopamine (DA) concentrations in the ST compared to those of age-matched saline-treated controls. However, a significant reduction in DA levels was observed in the OT and NA of old but not young rats treated with MPTP. In contrast, no changes in 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) levels in these three regions were seen in either young or old MPTP-treated rats. However, the ratio of DOPAC/DA and HVA/DA in the ST and NA were significantly higher in old MPTP-treated rats than those in old controls. The concentrations of DA, DOPAC and HVA remained unchanged in the SN and VTA of both young and old rats after MPTP treatment. These results indicate that multiple treatment of low-dose MPTP selectively causes more widespread damage to dopaminergic neurons in old rats than in young ones, and further support the view that effects of MPTP on the dopaminergic system in rats may depend on age. PMID- 7984339 TI - Basal magnocellular and pontine cholinergic neurons coexpress FGF receptor mRNA. AB - By in situ hybridization histochemistry, fibroblast growth factor receptor gene (flg)-expressing neurons were newly identified in the basal magnocellular nuclei (the vertical and horizontal limbs of the diagonal band, and Meynert's nucleus). The present study also confirmed flg localization in the laterodorsal tegmental nucleus and the pedunculopontine tegmental nucleus of the pons. Immuno- and in situ hybridization histochemistry on the same sections demonstrated that choline acetyltransferase and flg were colocalized in single neurons of the diagonal band, Meynert's nucleus and the pontine tegmental areas. The results suggest that a significant number of the basal magnocellular and a majority of the mesopontine cholinergic neurons are directly affected by fibroblast growth factors (FGF) via FGF receptor gene. PMID- 7984340 TI - Distribution of serotonin cells projecting to the pontomedullary reticular formation in the cat. AB - Using immunohistochemistry and retrograde transport techniques, this study demonstrates that serotonin (5-HT) cells in the dorsal tegmental gray of the pons at rostrocaudal from P1 to P6 levels are sources of bilateral serotonergic projections to the gigantocellular tegmental field of the medial pontine and medullary reticular formation in the cat. The cells observed were a relatively homogeneous population of small (30 microns) to medium-sized (40 microns) cells, oval, fusiform or spindle-shaped. Rostrally and caudally located 5-HT cells in the dorsal tegmental gray tended to project to the pontine and medullary reticular formation respectively. The dendrites of these cells spread in a plane perpendicular to the long axis of the brainstem. Thin 5-HT fibers with a series of fine varicosities (0.5-1.0 microns in diameter) surrounded reticular neurons, and some of these varicosities closely apposed the proximal dendrites and somata of the reticular neurons. Both large (50 microns) and small (20-30 microns) reticular neurons were uniformly innervated by 5-HT fibers. As revealed in the present study, the serotonergic system, together with the monoaminergic and cholinergic systems, seems to be involved in behavioral state regulation. PMID- 7984342 TI - Regulation of regional blood flow in the laterodorsal thalamus by ascending cholinergic nerve fibers from the laterodorsal tegmental nucleus. AB - The laterodorsal tegmental nucleus (LDT) is the largest aggregation in the brainstem of cholinergic neurons whose axons reach the thalamus as part of a diffuse projection to the forebrain. We measured the regional blood flow in the thalamus by means of laser Doppler flowmetry, and examined whether the blood flow was regulated by the ascending cholinergic nerve fibers originating in the LDT. Experiments were performed on urethane-anesthetized rats whose upper cervical spinal cord was transected to avoid response of systemic blood pressure following LDT stimulation. The ascending cholinergic nerve fibers were excited by electrical or chemical stimulation applied to the LDT. The regional thalamic blood flow increased in response to repetitive electrical stimulation and chemical stimulation with L-glutamate to the LDT. The response, starting several seconds after the onset of electrical stimulation and lasting as long as 1 min, was reduced by i.v. scopolamine, a cholinergic muscarinic receptor antagonist. The results indicate that regional blood flow in the thalamus is increased by excitation of the ascending cholinergic nerve fibers originating in the LDT mainly through the cholinergic muscarinic receptors. PMID- 7984341 TI - Roles of endogenous cholinergic neurons in the induction of long-term potentiation at hippocampal mossy fiber synapses. AB - To evaluate the functional role of endogenous acetylcholine (ACh) in the induction of long-term potentiation (LTP) at mossy fiber-CA3 synapses, the influence of cholinergic hypofunction on it was investigated. Administration of a cholinergic neurotoxin, ethylcholine mustard aziridinium ion (AF64A; 5 nmol, i.c.v.), to guinea pigs one week prior to preparing slices resulted in a significant decrease in the magnitude of LTP, associated with a significant decrease in cholineacetyltransferase (ChAT) activity and the number of ChAT immunoreactive cells in the hippocampal slices. Bath-application of a cholinesterase inhibitor, physostigmine at 0.1 microM and 10 microM, attenuated and augmented, respectively, the magnitude of LTP in slices prepared from vehicle treated animals (naive slices), whereas that in slices prepared from AF64A treated animals (lesioned slices) was not significantly affected by physostigmine at any concentration tested. The induction of LTP in naive slices was inhibited or facilitated by a muscarinic M1 antagonist pirenzepine (1 microM) and by an M2 antagonist AF-DX 116 (1 microM) alone, respectively, whereas that in lesioned slices was not significantly changed by either of them. Furthermore, bath-applied carbachol (CCh) at 0.01-10 microM augmented the magnitude of LTP in lesioned slices, whereas the induction of LTP in naive slices was inhibited and facilitated by CCh at 0.01-0.1 microM and 1-10 microM, respectively, as reported previously. Such an augmentation of LTP by CCh was reversed by pirenzepine, but not by AF-DX 116. These observations suggest that AF64A induces the defect in ACh release and the hypofunction of M2 receptors, but not of M1, at least during the induction of LTP at mossy fiber-CA3 synapses.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7984344 TI - The nutrition transition in low-income countries: an emerging crisis. AB - Scientists have long recognized the importance of the demographics and epidemiologic transitions in higher income countries. Only recently has it become understood that similar sets of broadly based changes are occurring in lower income countries. What has not been recognized is that concurrent changes in nutrition are also occurring, with equally important implications for resource allocation in many low-income countries. Several major changes seem to be emerging, leading to a marked shift in the structure of diet and the distribution of body composition in many regions of the world: a rapid reduction in fertility and aging of the population, rapid urbanization, the epidemiologic transition, and economic changes affecting populations in different and uneven ways. These changes vary significantly over time. In general, we find that problems of under- and overnutrition often coexist, reflecting the trend in which an increasing proportion of people consume the types of diets associated with a number of chronic diseases. This is occurring more rapidly than previously seen in higher income countries, or even in Japan and Korea. Examples from Thailand, China, and Brazil provide evidence of the changes and trends in dietary intake, physical activity, and body composition patterns. PMID- 7984343 TI - Intracellular calcium increase induced by GABA in visual cortex of fetal and neonatal rats and its disappearance with development. AB - To address the question of whether gamma-aminobutyric acid (GABA) induces a change in the concentration of Ca2+ in neurons of the developing visual cortex, and if so, to elucidate a developmental profile of such a GABA-induced change, we measured intracellular Ca2+ signals using microscopic fluorometry in visual cortical slices loaded with rhod-2. The slices were prepared from rat fetuses of embryonic day 18 (E18) and rat pups of postnatal days 0-30 (P0-P30). Application of GABA through the perfusate at 100 microM induced a marked rise in intracellular Ca2+ signals in the cortical plate and subplate at E18 and P0-P2. After P5 the GABA-induced rise in Ca2+ dramatically reduced, and at P20 and thereafter it became undetectable. At E18 and P0-P2 an agonist for GABAA receptor, muscimol, induced a Ca2+ rise in the same way as did GABA, while a GABAB receptor agonist, baclofen, did not induce any significant rise in Ca2+ signals. Also, a GABAA receptor antagonist, bicuculline, blocked the GABA-induced rise in Ca2+ signals. These results indicate that the Ca2+ rise is triggered by activation of GABAA receptors. The application of Ni2+ at a concentration high enough to block all types of voltage-dependent CA2+ channels prevented the Ca2+ signals from increasing in response to GABA application, suggesting that Ca2+ may be influxed through such channels following depolarization evoked by GABA. PMID- 7984345 TI - Retinoids and the skin. AB - Retinoids are a group of naturally occurring and synthetic compounds with vitamin A-like biological activity. They play an important role in vision, reproduction, growth, and epithelial cell differentiation. Recent discoveries of specific retinoid cellular binding proteins and nuclear receptors have led to a better (although not complete) understanding of the complex mechanisms of retinoid action. Numerous clinical studies have demonstrated beneficial effects of retinoids on skin diseases such as acne, psoriasis, ichthyoses, keratodermas, skin cancers and their precursors, as well as a reversal of the effects of photoaging. PMID- 7984346 TI - Iron-copper interactions: some new revelations. AB - Iron and copper show an uncommon but largely unexplained interdependence, the basis for which is being clarified in hemoglobin-synthesizing cells, yeast, and photosynthetic microorganisms. The interactions of the two metals with membrane transport systems and genetic regulators are more apt to be cooperative than antagonistic. PMID- 7984347 TI - Professional roles of dietitians: do dietitians and physicians agree? AB - In some quarters, dietitians and physicians do not agree on a role for dietetic practitioners. Dietitians seem to be more highly regarded, and their counsel is sought and advice heeded when both health professionals work on developing collegial relationships. Education matters: a course in nutrition for physicians to-be and more depth in the sciences for dietetic students are major factors in establishing partnerships in patient care. PMID- 7984348 TI - Identification of the triggers of celiac sprue. AB - Three theoretically antigenic synthetic peptide subunits of alpha-gliadin were evaluated in vivo in four patients with celiac disease. A sequence of alpha gliadin (amino acids 31-49) was toxic in all patients, suggesting that this sequence is one of the triggers of the immune system in celiac sprue. PMID- 7984349 TI - Bioelectrical impedance and body composition: present status and future direction. PMID- 7984350 TI - Gene expression in suprachiasmatic nucleus and circadian rhythms. AB - The suprachiasmatic nuclei (SCN) contain a circadian system consisting of circadian oscillator (clock) that is normally synchronized by the light/dark cycle (input) and drives circadian rhythms (output) that are intrinsic to the SCN. Gene expression of immediate-early genes, such as c-fos and jun-B, in the ventrolateral SCN is associated with circadian synchronization by light pulses and subjected to circadian control. Vasopressin and somatostatin gene expression shown distinct circadian rhythms intrinsic to the dorsomedial SCN with higher peptide levels occurring during the day. In addition, embryonic SCN grafted into the brain of an SCN-lesioned arrhythmic host define the period of the restored circadian locomotor rhythm. Taken together, these and other findings support the notion that the expression of genes underlying circadian synchronization, oscillation and output takes place within individual SCN neurons. However, no information regarding the nature and number of those neurons as well as the molecular mechanisms of the single cell-circadian oscillator and output is currently available. Therefore, we propose a simple two-neuron model as a framework for critically discussing the molecular genetic strategies to analyze the circadian system in SCN. PMID- 7984351 TI - 5-HT1A receptor influences on rodent social and agonistic behavior: a review and empirical study. AB - Investigations examining the influence of 5-HT1A receptors in murine agonistic and social behavior have reported either specific or nonspecific attenuation of offensive behavior. To clarify this situation, the effects of three 5-HT1A agonists were examined on isolation-induced aggression and social behavior in male mice. 8-OH-DPAT (0.025-1.25 mg/kg) increased social behavior, rearing, and digging. Offensive behavior was reduced, without concomitant sedation. Ipsapirone (0.1-10.0 mg/kg) reduced naso-nasal behavior, whilst enhancing stretched-attend behavior, cage-exploration, and rearing. Offensive and defensive behaviors were attenuated, without reductions in activity. MDL 73005 EF (0.25-8.0 mg/kg) reduced social behaviors, cage-exploration and rearing while maintenance behavior was increased. Offensive and defensive behaviors showed attenuation. Current results corroborate previous findings with respect to 5-HT1A receptor involvement in murine agonistic behavior and anxiety. Data also connote that the behavioral specificity of 5-HT1A ligands should be interpreted in terms of response competition rather than solely concomitant sedation. PMID- 7984352 TI - Neural substrate of defensive behavior in the midbrain tectum. AB - It has been shown that the gradual increase in the intensity of electrical stimulation of the dorsal periaqueductal gray (DPAG), deep layers of the superior colliculus (DLSC) and inferior colliculus of rats induces, in a progressive manner, characteristic aversive responses such as arousal, freezing, and escape behavior. The DPAG-DLSC together with the periventricular gray substance of the diencephalon, amygdala and the inferior colliculus, constitute the neural substrate of aversion in the brain. In general, the behavioral responses induced by midbrain tectum stimulation are accompanied by increases in the mean arterial blood pressure, heart rate, and respiration. Both the behavioral and autonomic consequences of electrical stimulation of the mesencephalic tectum have been shown to be attenuated by minor tranquilizers, probably through enhancement of GABAergic neurotransmission. Besides GABAergic mechanisms several lines of evidence have clearly implicated opioid, serotonergic, and excitatory amino acids mediated mechanisms in the control of the neural substrates commanding defensive behavior in the brain aversive system. PMID- 7984353 TI - Caveats in the study of perinatal behavioral development: utility of fetal study. AB - Study of behavior during development presents psychobiologists and neurobiologists with a unique set of problems that should be addressed in the design and analysis of experiments. Some of these caveats have become apparent only with the recent growth in research with subjects around the time of birth. For example, physiological regulation within the maternal-infant dyad, litter effects, the influence of context at the time of testing on performance, and dissociation of age-related change and experience, all are important experimental considerations in developmental study. Manipulation and measurement of behavioral variables in the fetus in vivo can provide one means for circumventing many of the methodological pitfalls that are associated with behavioral study of newborn subjects. PMID- 7984354 TI - Recent developments in the behavioral pharmacology of benzodiazepine (omega) receptors: evidence for the functional significance of receptor subtypes. AB - Recent research in molecular biology has demonstrated the complexity of GABAA receptors and shown that benzodiazepine (BZ-omega) receptor subtypes have a structural reality. It is therefore appropriate to ask whether the different pharmacological effects produced by benzodiazepines (anticonvulsant activity, anxiety reduction, motor incoordination, learning deficits, characteristic discriminative stimulus effects, tolerance and dependence) are associated with activity at different receptor subtypes. The present paper reviews the literature dealing with the behavioral effects of novel BZ (omega) receptor ligands relevant to the question of the functional significance of the BZ1 (omega 1) and BZ2 (omega 2) receptor subtypes. The only drugs currently available with a considerable degree of selectivity are alpidem and zolpidem. These compounds have relatively high affinity for GABAA receptors containing the alpha 1 subunit (corresponding to the BZ1 (omega 1) subtype) and very low affinity for receptors with the alpha 5 subunit (corresponding to one type of BZ2 (omega 2) receptor). Pharmacological effects observed with these, and other, less selective compounds allow several tentative conclusions to be drawn: (a) Little is known of the role of subtype selectivity in anxiolytic or amnestic effects but compounds with low intrinsic activity may reduce anxiety without giving rise to sedation or motor incoordination and BZ1 (omega 1) selective drugs appear to disrupt memory only at sedative doses; (b) Selectivity for BZ1 (omega 1) receptors may be associated with sleep-inducing activity but not with motor incoordination, suggesting that BZ2 (omega 2) receptors may be of particular importance in mechanisms of muscle relaxation; (c) The discriminative stimulus effects of different BZ (omega) receptor ligands are not identical and differences may be related to receptor selectivity; (d) Compounds with BZ1 (omega 1) selectivity and compounds with low intrinsic activity produce little or no tolerance and dependence. A wider range of selective compounds will be necessary to investigate these factors in detail and many different pharmacological profiles can be expected from drugs with selectivity and different levels of intrinsic activity. PMID- 7984355 TI - Physical dependence produced by central morphine infusions: an anatomical mapping study. AB - Morphine sulfate (1.5 nmoles/h) was chronically infused into various brain regions in rats. After 72 h of continuous infusions, an intraperitoneal injection of naloxone hydrochloride (5 mg/kg) was given to determine if physical dependence had developed. Various withdrawal signs were present following the naloxone challenge in rats chronically infused with morphine into the periventricular gray region. These withdrawal signs included escape behavior, wet-dog shakes, and teeth chattering. Several other brain regions (e.g., amygdala, caudate nucleus, lateral hypothalamus, nucleus accumbens, thalamus) were also tested, but morphine infusions into these areas produced only slight physical dependence. The magnitude of physical dependence produced by morphine infusions into the rostral aspect of the periventricular gray was comparable to that seen following repeated systemic morphine injections, while the physical dependence produced by caudal infusions into the vicinity of the locus coeruleus was considerably less. These data confirm the importance of the periventricular gray region in the development of physical dependence on morphine and reveal that a drug action in the more rostral aspect of this brain region produces the strongest signs of physical dependence. PMID- 7984356 TI - Allostasis, amygdala, and anticipatory angst. AB - Regions of the amygdala are involved in anticipation of negative events. Chronic anticipation of negative events leads to what we call allostatic load, or arousal pathology. Two hormones appear to be involved in arousal pathology; corticotropin releasing hormone in the brain and glucocorticoids. We suggest that increases in corticotropin-releasing hormone, by stress or glucocorticoids, in the amygdala may have functional consequences for allostatic load. Whereas, corticotropin releasing hormone in the parvocellular region of the paraventricular nucleus of the hypothalamus is decreased by glucocorticoids thereby under negative feedback and homeostatic control, the central nucleus of the amygdala is to some extent under positive feedback and is increased by glucocorticoids, and perhaps under allostatic control. The human and animal literature suggest that a variety of psychopathologies (e.g., melancholia) may be tied to neurohormonal signals activating regions of the amygdala. PMID- 7984357 TI - Impaired brain microcirculation may trigger Alzheimer's disease. AB - A working hypothesis on the pathogenesis of Alzheimer's disease (AD) is presented. The model is based on recent ultrastructural and classic histologic findings showing extensive and characteristic distortion of brain capillaries in Alzheimer brains. Brain capillary distortion induces normal laminar flow to become microturbulent or "disturbed", an outcome which over the course of many years can modify hemorheologic and hemodynamic flow patterns. As flow patterns become disturbed, micronutrient delivery to the brain is reduced thus compromising neurono-glial interaction. Catabolic outflow of CNS waste products is also depressed. When ischemic sensitive neurons, particularly in the CA1 sector, are unable to meet energy demands from lowered energy supply, they release astroglial mitogens signalling reactive astrocytes to proliferate. The resulting neuronal energy crisis is consequently complicated by the increased density of reactive astrocytes which ostensibly contribute to senile plaque development and neurofibrillary tangle formation as competition for nerve tissue space increases. The suboptimal delivery of glucose, oxygen, essential nutrients and protease regulators in AD brain becomes progressively unpredictable and in time yields to a linear decline of neurochemical, morphologic and cognitive functions. PMID- 7984358 TI - Interacting brain stem components of opiate-activated, descending, pain inhibitory systems. AB - This is a review of research aimed at elucidating how various opiate analgesia substrates in rat brain stem interact with one another to bring about opiate analgesia. The three substrates studied are the midbrain periaqueductal grey (PAG), the bulbar nucleus raphe magnus (RM), and the bulbar nucleus reticularis paragigantocellularis (PGC). The methods used in the reviewed studies are unique in that behavioral and neuronal responses are assessed in consequence of nanoinjecting opiates (met-enkephalin) into subset pairs of these structures. Responses to single and conjoint injections are compared. Effects on neuronal and behavioral responses in consequence of disruption of these structures with tetracaine block are also discussed. It is seen that PGC cannot serve as an opiate analgesia substrate if the functional integrity PAG is impaired. However PAG does not depend on PGC's functional integrity. PMID- 7984359 TI - Kindled epileptic seizures, postictal refractoriness, status epilepticus, and electrical self-stimulation. AB - A single stimulus applied once daily to the limbic system commonly leads to convulsive seizures yet seizures are relatively infrequent during intracranial self-stimulation (ICSS), a procedure that involves many hundreds of similar stimuli. The present study examined the possible role of electrode site, interstimulus interval, afterdischarge and reinforcement thresholds and postictal refractoriness in accounting for this paradox. Electrode location was an overriding factor: seizures were never seen with hypothalamic implants posterior to the level of the ventromedial nucleus but were elicited by the majority of more rostral reward sites. Frequent repeated stimulation by ICSS did not in itself prevent subsequent kindling or reverse the effects of earlier kindling; on the contrary, seizures induced by ICSS showed a progressive increase in severity similar to the progression produced by conventional kindling. Individual convulsive seizures, as in previous studies, conferred transient protection against further seizures whether from ICSS or from kindling. More prolonged protection occassionally developed after repeated convulsive seizures: protection was accompanied by continuous EEG slow-waves corresponding in presentation to clinical petit mal status. Prolonged resistance to seizures has also been reported after tonic-clonic status epilepticus causing temporal lobe damage. The relative infrequency of seizures during ICSS ordinarily appears to depend on the siting of the electrodes, on distinct short- and long-term postictal refractory states, and on the rat learning to restrict stimulus input to subseizural levels. PMID- 7984360 TI - Growth hormone-regulatory peptides (GHRH and somatostatin) and feeding: a model for the integration of central and peripheral function. AB - The present paper provides an overview of findings that implicate growth hormone releasing hormone (GHRH) and somatostatin (SS), the two peptides that regulate growth hormone secretion, in the central regulation of feeding. Evidence is presented that GHRH and SS increase food intake, in the rat, via a common centrally mediated mechanism involving the suprachiasmatic nucleus. Food intake is increased by increasing motivation to eat as evidenced by facilitation of operant behavior. Macronutrient-choice studies indicate that GHRH (and possibly SS) selectively facilitate protein consumption. Time of day is also important, with evidence that endogenous GHRH and SS-induced feeding is most strong in the early nocturnal period. GHRH and SS, together with other nutrient-specific signals, such as neuropeptide Y, noradrenaline and galanin, may determine the circadian expression of food intake in animals. Other behavioral and physiological effects of these peptides, both central and peripheral, are reviewed in the context of a possible mechanism by which these peptides integrate diverse, but complimentary, central and peripheral functions related to nutrition, metabolism and growth. PMID- 7984361 TI - Practical aspects of indirect calorimetry in laboratory animals. AB - Oxidation of the energetic substrates by the body is associated with oxygen consumption, carbon dioxide production, and heat release specific to the nature of the energetic substrates being oxidized. Therefore, measurement of respiratory exchanges (indirect calorimetry) is a powerful method to investigate heat production of a living organism. In this article, we review the elementary principles of indirect calorimetry and describe the operating principle of the two most typical devices used to perform indirect measurements of energy expenditure in the laboratory animal: the closed-circuit and the open-circuit. We then discuss some practical aspects of the day-to-day use of these devices: respective advantages and limitations of each technique, data processing, calibration, correction for body-size, and computation of the energy expended for activity. In the second part, we review some of the standard formulas of indirect calorimetry that offer the possibility to obtain more precise information such as the rate of oxidation of carbohydrates (CHO), lipids and proteins if some hypotheses are made on the intensity of lipogenic, ketogenic, and gluconeogenic processes. Finally, a practical example of the measurement of energetic cost of activity and thermic effect of food in the rat is given. PMID- 7984362 TI - Jerzy Konorski (1903-1973) on the 20th anniversary of his death. AB - This article describes the pioneer research of Jerzy Konorski on voluntary motor conditioned reflexes type II (CRIIs or instrumental CRs). Some of his publications on topics such as four varieties of CRIIs, switching, and ability of transformation (plasticity) of CRIIs are briefly summarized. Konorski's theoretical views including criticism of some of Pavlov's interpretations are also presented. A few events connected to Konorski's scientific activities are mentioned. PMID- 7984363 TI - Office H&S: what you always wanted to ask. PMID- 7984364 TI - Lightening the load: physiotherapy in industry. PMID- 7984365 TI - Noise: an aggravating quality of sound. PMID- 7984366 TI - Acoustic mechanisms in middle ear sound transfer. AB - This article reviews the mechanisms involved in the sound conduction process. This review includes both the physics of sound energy and the system of sound transmission through the middle ear. Several basic clinical defects of the middle ear are described as to their influence on sound conduction along with typical audiometric patterns associated with these defects. PMID- 7984367 TI - Biomaterials in ossiculoplasty and history of development of prostheses for ossiculoplasty. AB - From 1956 to the present has been a period of surgical expansion into the middle ear for correction of deafness. This article follows the evolution of microscopic implants designed to replace all or part of the ossicular chain, and the use of biocompatible materials of plastic, metal, and ceramics to form prosthetic devices. PMID- 7984368 TI - Experimental models of ossiculoplasty. AB - Measurement of the acoustic properties of middle ear prostheses in an appropriate model prior to insertion in humans should be part of the routine of the prosthesis development and testing process, but it is not. This article describes a human temporal bone model suitable for such testing and discusses the results of several commonly used prostheses evaluated in the model. By comparing existing and new experimental prostheses in such a model, we should be better able to develop prostheses capable of providing improved hearing results following middle ear reconstruction. PMID- 7984369 TI - Incus interposition and ossiculoplasty with hydroxyapatite prostheses. AB - This article traces the evolution of transplant material in ossicular reconstruction of the middle ear. The first transplant consisted of the body and short process of the homograft incus. It was repositioned or wedged between the stapes head and the manubrium of the malleus. Further modification consisted of the sculpture of prostheses from homograft incudes; these were known as the notched incus with short or long process. By means of a notch in the short process, they were locked in place. The final phase is the use of hydroxyapatite as a biocompatible material from which similar prostheses may be precisely manufactured. These hydroxyapatite prostheses, known as the incus and incus stapes replacement prosthesis, appear to be well tolerated and to produce excellent hearing results. PMID- 7984370 TI - Ossicular chain reconstruction. Capitulum to malleus. AB - Ossicular chain reconstruction is most commonly performed for an absent or diseased incus. Reestablishing continuity by placing a strut prosthesis between the stapes capitulum and malleus handle minimizes the possibility of extrusion and displacement. Strut prostheses are made of hydroxyapetite, which is a highly biocompatible material that bonds to living bone. PMID- 7984371 TI - Ossiculoplasty with presculpted banked cartilage. AB - The use of self-stabilizing, presculpted cartilage homografts for middle ear reconstruction has an established track record with long-term results equivalent to reconstruction methods using alloplastic material. This method affords several advantages over other techniques, which will be discussed in detail. PMID- 7984372 TI - Ossiculoplasty with composite prostheses. PORP and TORP. AB - This article discusses the design of a composite prosthesis developed from a desire to combine the advantages of two synthetic materials. Hydroxyapatite can be used directly against the tympanic membrane, and Plastipore can be easily trimmed intraoperatively. The need for any human tissue can be eliminated; hearing results and extrusion rates appear comparable to other implants commonly used. PMID- 7984373 TI - Ossiculoplasty with semibiologic and composite prostheses. AB - The Lippy-modified Robinson prosthesis has been used for years in revision stapedectomy and has proved successful in reconstructing the absent lenticular process. When this technique fails, an ossicle cup prosthesis can be used. The ossicle cup and columella have been used for 20 years with continuing success. The advantages of the semibiologic prostheses are as follows: The prosthesis can be sized as each case requires, giving a variable height above the remaining stapes. The prosthesis is designed not to touch the promontory or facial nerve canal. The synthetic portion of the semibiologic prosthesis does not touch the tympanic membrane. An efficient perpendicular action is achieved from the tympanic membrane to the stapes footplate. The prosthesis remains in place during tympanic membrane movement. A stable dynamic joint is provided with the stapes capitulum (ossicle cup). A safe platform is provided that distributes the weight of the assembly prosthesis over the entire stapes footplate (ossicle columella). Although both semibiologic prostheses are used routinely for partial and total ossicular replacement, other troublesome and technically difficult ossicular reconstruction problems can also be solved by the adaptability of the synthetic portion of the prosthesis. Because the synthetic portion of the prosthesis can be modified by notching, shaping, and trimming, the following problems can be overcome: A laterally healed tympanic membrane can be reached by increasing the length of the synthetic shaft. In the absence of the stapes capitulum, the cup is notched in two places (180 degrees apart) to fit the shoulders of the remaining stapes. Remaining crura on the footplate can be bypassed by trimming the synthetic footplate to fit in between the crura. The stapes with a low profile can be utilized by increasing the length of the synthetic shaft. An abnormal stapedial tendon attachment to the stapes capitulum can be overcome with a single notch in the cup. An overhanging facial nerve can usually be bypassed by the narrow design of the ossicle columella. The future of ossiculoplasty will rest more on the solution of ancillary problems than on ossiculoplasty techniques. These troublesome ancillary problems include eustachian tube dysfunction, cholesteatoma control, mucosa regeneration, and fibrosis during the healing process. The self-correcting process of ossiculoplasty is an evolutionary process, and the small surgical steps taken are slowly incorporated into surgical principles. Incorporating a synthetic prosthesis within a natural or synthetic ossicle is a logical and evolutionary step in the science of ossicular reconstruction. PMID- 7984374 TI - Ossiculoplasty with composite prostheses. Overview and analysis. AB - Aeration of a mucosa-lined tympanic cavity is essential for a functioning middle ear. Extrusions of even the best-designed prostheses occur from abnormal middle ear conditions such as atelectasis, middle ear fibrosis, recurrent cholesteatoma, tympanic membrane perforation, and otitis media. Various polymers have been developed in an attempt to maximize prosthetic biocompatibility and ease of use while minimizing the chance of extrusion. One such polymer is a composite of hydroxyapatite and Silastic, known as Flex H/A. This material has been incorporated into two ossicular prostheses, the Universal Plus and the Causse Flex H/A prostheses. Certainly, refinements will continue to be made in the chemical makeup of the bioceramics in order to achieve optimal biocompatibility. In addition to biocompatibility, cost containment issues have influenced the development of ossicular prostheses. A universal prosthesis eliminates the need to stock multiple designs, thereby reducing the cost to institutions. One of the greatest challenges in the future will be to define the appropriate prosthetic design for optimal sound transmission. Consideration of prosthesis weight, head size, and footplate attachment are future research questions that need to be addressed in a scientific biologic model. PMID- 7984375 TI - Ossiculoplasty with polymaleinate ionomeric prostheses. AB - This article discusses the role of the new Ionomeric middle ear prostheses for ossicular chain reconstruction. Although the prostheses are composed of a rigid alloplastic material, they can be easily sculpted to conform to the middle ear anatomy. PMID- 7984376 TI - Total reconstruction of the ossicular chain. AB - The footplate only situation remains the greatest challenge of ossicular reconstruction. This article discusses the long term results obtained with a new type of columella, the Spandrel, which combines the rigidity necessary for sound transmission with the flexibility required to comply with the dynamic movements of the neotympanum. PMID- 7984377 TI - Ossiculoplasty in congenital hearing loss. AB - We have presented an extensive review of congenital ossicular anomalies. These deformities occur in combination with one another or as isolated problems with equal frequency. They are so rare that even the busiest otologists have limited clinical experience with them. The astute otologist will keep these facts in mind when assessing congenital middle ear problems in the office and in the operating room. Careful, detailed history taking may reveal the presence of familial conductive hearing loss or other congenital syndromes. Complete head and neck examination as well as observation of the extremities may provide clues to the otologic diagnosis. Microscopic examination of the ear reveals abnormalities of the tympanic membrane, malleus, and incus. Audiometric and radiologic evaluation augments physical examination. At surgery, the otologist must be prepared to perform a variety of possible surgical procedures, from traditional ossiculoplasty and stapedectomy to fenestration. Hearing aids are an option for patients with congenital ossicular anomalies, and the possibility of inoperability must be kept in mind; the patient must be prepared for this eventuality. Congenital ossicular anomalies present a challenge to the otologic surgeon, and their successful treatment, the greatest reward. PMID- 7984378 TI - Histopathology of ossicular implants. AB - Ossicular and cortical bone grafts maintain their morphologic structure for long periods of time and show varying amounts of replacement of nonviable bone by new bone through a slow process of creeping substitution. Cartilage grafts develop chondromalacia, lose stiffness, and tend to be resorbed over time. Plastipore prostheses elicit foreign body giant cell responses with microscopic biodegradation of the implants. There is a great need for the study of well documented human temporal bone cases with in situ ossicular implants. PMID- 7984379 TI - Results and outcomes in ossiculoplasty. AB - This article presents a series of goals and questions for future research in ossiculoplasty. Important technical questions include what are the best materials, prosthesis shapes, and techniques of placement for both immediate and long-term success. Important clinical questions include what improvements in communication should we expect, how should cases be selected, and how should patients be counseled. There are many variables that could affect reported results, including the selection of cases, audiometric techniques, the frequencies of hearing measurement, and the methods of data analysis. These are all discussed in this article. PMID- 7984380 TI - Mastering pediatric cardiopulmonary resuscitation. AB - Premature and unexpected death, especially in children, is tragic and very unacceptable. Effective treatments for sudden death of pediatric patients continue to emerge. Modern cardiopulmonary resuscitation function began with the widespread introduction of closed-chest cardiac massage in 1960; however, despite 35 years of research and refinement, more than 90% of children who receive cardiopulmonary resuscitation do not survive. This article summarizes and expands on current treatment concepts for pediatric sudden death. Emphasis is placed on procedures and techniques that likely are accessible in most medical centers caring for critically ill and injured children. PMID- 7984381 TI - Emergency alternatives to intravenous access. Intraosseous, intratracheal, sublingual, and other-site drug administration. AB - Difficulties and delays in establishing intravenous access are not uncommon in emergency situations in pediatrics. Alternatives to venous cannulation exist, including intraosseous access, intratracheal drug administration, sublingual and intralingual injection, the intrapenile route, and intracardiac injection. Each of these emergency alternatives to intravenous access is discussed from the historical, technical, utilitarian, and risk-benefit aspects. It is concluded that the intraosseous effective alternative to intravenous access in emergency situations. PMID- 7984382 TI - The injured child. An approach to care. AB - Injury is the leading cause of childhood death and disability in this country and has been for over a decade. Examination of the current injury statistics clearly demonstrates the failure of our present prevention strategies. Unless definitive steps are undertaken to initiate a comprehensive national injury prevention program, this tragic impact upon children will continue. To ensure that optimal care for injured children is provided, several criteria must be met. Seriously injured children require skillful assessment by clinicians experienced in pediatric trauma and rapid evacuation to a regional pediatric trauma center when appropriate. Their care is best provided by a multidisciplinary team including intensivists, surgeons, and rehabilitation specialists, all thoroughly familiar with the types of injuries children sustain. In the ICU, careful monitoring of circulatory, respiratory, renal, and neurologic status combined with early intervention for physiologic derangements maximizes the injured child's chances for recovery. Finally, it is important to understand that care for the injured child spans a continuum beginning with prevention, continuing through acute care, and ending only after rehabilitation and reintegration into the community is complete, and that each component is no less important than another. Only through these efforts can the loss of our nation's most precious resource be avoided. PMID- 7984383 TI - Therapeutic drug monitoring in the pediatric intensive care unit. AB - Drugs are administered in the pediatric intensive care unit using either a target effect or a target-concentration strategy. In the former, drug dose is escalated until the predetermined target-effect is achieved, no further pharmacologic effect is obtained with incremental increases in dose, or toxicity supervenes. When the target-concentration strategy is used, drug therapy is adjusted to achieve serum/plasma drug concentrations within an accepted therapeutic range. This strategy does not recognize interindividual differences in drug responsiveness. Therapeutic drug monitoring in the pediatric intensive care unit is further confounded by the limited data available concerning the effects of the other technologies used on drug disposition and the paucity of information related to therapeutic agents in pediatric patients. Clearly therapeutic drug monitoring in the pediatric intensive care unit is a daunting challenge. PMID- 7984384 TI - Nosocomial infections in the pediatric intensive care unit. AB - Pediatric intensive care units have contributed considerably to the management of children with severe diseases and life-threatening conditions. The use of mechanical ventilation, invasive monitoring, and indwelling catheters increase the risk for nosocomial infection. Improving infection control practices and surveillance can significantly reduce the incidence of nosocomial infections. PMID- 7984385 TI - The critical care aspects of child abuse. AB - Child abuse is an all too prevalent disorder showing no signs of subsiding. When injuries from abuse or neglect are severe enough to threaten life or organ system function, the victims are admitted to the PICU for management. In this article, we elucidated aspects of caring for abused children that are unique to this entity. A case was presented that illustrates the complexity of the juxtaposition of social and legal and medical issues that invariably occurs in these situations. A general approach to diagnosis and management of these cases was discussed and several more specific conditions were examined in greater detail. This is an effort to clarify findings specific to abused children and to integrate these with accepted pediatric intensive care practices. Above all, however, we the authors hope to have reinforced the reader's understanding of his or her role as an advocate for these unfortunate children. In guiding them through the labyrinth of medical, social service, and legal systems, we as physicians must not forget their helplessness. PMID- 7984386 TI - Pain management and sedation in the pediatric intensive care unit. AB - Several situations arise in the PICU patient that require the administration of drugs for sedation and analgesia. A "cookbook" approach is impossible because of the diversity of patient and clinical scenarios. When amnesia is required, these authors prefer a continuous infusion of a benzodiazepine such as midazolam or lorazepam. Although the majority of clinical experience has been with midazolam, lorazepam either by bolus dose or continuous infusion offers a cost-effective alternative. When analgesia is required, the addition of a continuous infusion of narcotic or the use of a PCA device in the older patient should prove effective. Although fentanyl is frequently chosen, morphine is an effective and cost effective alternative for patients with stable cardiovascular function. The synthetic narcotics are recommended for neonates, especially following cardiac surgical procedures and those at risk for pulmonary vasospasm. Narcotics may also be used for the treatment of agitation in those situations that do not necessarily require analgesia. Our clinical experience suggests that narcotics may be more effective for sedation than benzodiazepines in children less than 1 year of age. When the above agents fail to be effective or are associated with cardiovascular depression, alternatives may include ketamine or pentobarbital. Ketamine may be useful for the unstable patient or those with a bronchospastic component to their disease process. We have found pentobarbital to be effective when the combination of benzodiazepines and narcotics fails to provide the desired level of sedation. Aside from these techniques, regional anesthesia may offer a more effective means of controlling pain in the PICU patient. These techniques may be effective when parenteral narcotics are inadequate or lead to undesired effects. Although most commonly used for postoperative analgesia, their use in patients with pain from other causes (e.g., multiple trauma) may be indicated, especially when parenteral narcotics may interfere with respiratory function or the ongoing assessment of the patient's mental status. PMID- 7984387 TI - Treatment of critical status asthmaticus in children. AB - Status asthmaticus is complex in its etiology and pathophysiology and may be associated with significant morbidity and mortality. Although there are many therapeutic options, specific inhaled beta 2-agonists, corticosteroids, and oxygen remain the mainstay of therapy. Several new drugs and some older drugs are being used in management; their exact role in treatment at present, however, relies largely on personal preferences. Innovative methods of providing ventilatory support are also emerging. What is quite clear is the fact that involvement of specialists (pulmonologists and intensivists) early in the course of severe status asthmaticus is needed to ensure optimal management and possibly favorable outcomes. PMID- 7984388 TI - Novel therapies for acute respiratory failure. AB - Mortality in acute respiratory failure in the non-neonatal pediatric patient has not changed substantially in 20 years, despite advances and refinements in conventional therapeutic strategies and technology. A host of innovative therapies are currently in various stages of investigation, including high frequency ventilation, pressure control ventilation, permissive hypercapnia, extracorporeal membrane oxygenation, exogenous surfactant administration, inhaled nitric oxide, and liquid ventilation. While none of these therapies has yet been prospectively studied in non-neonatal pediatric patients, all show much promise by virtue of their emphasis on either directly addressing pathophysiologic derangements associated with acute respiratory failure or by reducing the complications associated with conventional therapy. PMID- 7984389 TI - Viral respiratory infections. AB - Viral infections constitute more than 60% of acute lower respiratory illnesses. Respiratory syncytial virus (RSV) and parainfluenza viruses are the most frequent etiologic agents. After transmission by large droplet aerosol or direct contact, the viruses gain entry into host cells through specific viral surface proteins; subsequently, pathogenetic mechanisms cause tissue injury and result in clinical disease. In the intensive care unit the mainstay of treatment is primarily supportive. Nonspecific treatment may include nebulized beta-agonists, aminophylline, and steroids. Ribavarin is the only specific antiviral agent approved for respiratory syncytial virus infection but its efficacy remains controversial. New therapies and vaccines offer hope for improved outcome from viral respiratory infections such as RSV. PMID- 7984390 TI - Autopsies and the pediatric intensive care unit. AB - The pediatric autopsy can provide great benefits to families at a time when their world is falling apart. It can be invaluable in the processing of grief that families endure, helping them to plan their future. Autopsy results not only provide information but may also provide consolation by giving the family the opportunity to discuss the disease process that resulted in death. Autopsy results also provide information regarding the future and reassurance that appropriate care was given. Failure to perform a postmortem examination denies the family and the clinician knowledge regarding mechanisms of disease, confirmation or inclusion of unsuspected diagnoses, and the presence of iatrogenic complications. This missed information can be both informative to the current family's situation and potentially therapeutic in future cases. If death is the final chapter of life, then the physician's responsible relationship with the parents of the deceased patient should not end until a conference takes place several weeks or months after the child's death. The results of the postmortem examination provide a beginning point for discussion regarding the child's illness and death, the parents responses and coping, and the opportunity to help the family make sense of and bring closure to one of life's greatest crises. PMID- 7984391 TI - Enhancing communication. The physician and family in the pediatric intensive care unit. AB - How well does the intensivist communicate with the parents of critically ill children? The authors' experience suggests that this process can be enhanced in a number of ways. The article reviews methods to improve communication by emphasizing the importance of the first meeting, trust, and understanding parental needs and coping mechanisms. PMID- 7984392 TI - Ethical issues in the pediatric intensive care unit. AB - Advanced technology and better scientific understanding of mechanisms of disease now permit intensive care personnel to extend life beyond what some patients and families consider reasonable, leading, in part, to the "patients' rights" movement and the articulation of legal and moral guidelines for foregoing life support. In the case of pediatrics, commentaries on a few of the topics that have arisen most frequently or have provided the greatest challenge in the authors' experience are provided. PMID- 7984393 TI - Outcome evaluations as measures of quality in pediatric intensive care. AB - In recent years, interest in assessing quality of care has blossomed. Quality care may be defined as providing the most appropriate treatment and providing it with great technical and managerial skill and proficiency in a manner that gains patient acceptance. For assessment purposes, variation in risk-adjusted outcomes between providers should be attributable to quality of care differences. Some methods for measuring outcomes and risk-adjustment for pediatric intensive care populations have been developed, but additional tools are needed for applications in outcomes management, continuous quality improvement, and outcomes research. PMID- 7984394 TI - Minimal spectral contrast of formant peaks for vowel recognition as a function of spectral slope. AB - In four experiments we investigated whether listeners can locate the formants of vowels not only from peaks, but also from spectral "shoulders"--features that give rise to zero crossings in the third, but not the first, differential of the excitation pattern--as hypothesized by Assmann and Summerfield (1989). Stimuli were steady-state approximations to the vowels [a, i, e, u, o] created by summing the first 45 harmonics of a fundamental of 100 Hz. Thirty-nine harmonics had equal amplitudes; the other 6 formed three pairs that were raised in level to define three "formants." An adaptive psychophysical procedure determined the minimal difference in level between the 6 harmonics and the remaining 39 at which the vowels were identifiably different from one another. These thresholds were measured through simulated communication channels, giving overall slopes of the excitation patterns of the five vowels that ranged from -1 dB/erb to + 2 dB/erb. Excitation patterns of the threshold stimuli were computed, and the locations of formants were estimated from zero crossings in the first and third differentials. With the more steeply sloping communication channels, some formants of some vowels were represented as shoulders rather than peaks, confirming the predictions of Assmann and Summerfield's models. We discuss the limitations of the excitation pattern model and the related issue of whether the location of formants can be computed from spectral shoulders in auditory analysis. PMID- 7984395 TI - Object-based apparent motion. AB - The interpretation of a dynamic visual scene requires integrating information within frames (grouping and completion) and across frames (correspondence matching). Fragmentary views of objects were used in five experiments. These views could not be matched with each other by any similarity transformation on the basis of their explicit visual features, but their completed versions were related by a rotational transformation. When the fragmentary images were successively presented to observers, it was found that they produced apparent motion in the picture plane and in depth. Thus, apparent motion is capable of establishing correspondence at the level of perceptually recovered objects in three-dimensional space. PMID- 7984396 TI - Text-contingent color aftereffects: a reexamination. AB - Five experiments reexamined color aftereffects contingent on the semantic properties of text (Allan, Siegel, Collins, & MacQueen, 1989). The influence of different assessment techniques and the effect of eye movements and overlapping contour information on the induction of color aftereffects by word and nonword letter strings were determined. Experiment 1 showed that no aftereffect was found when a traditional method of assessing color aftereffects was used. Experiments 2 and 4 demonstrated color aftereffects for both words and nonwords, but only when subjects fixated the same locus during induction and testing and only when assessed with the technique described by Allan et al. (1989). If, however, eye movements were made during induction, no color aftereffect was obtained (Experiment 3). Induction to nontext patterns with properties similar to those of text but with fewer overlapping contours resulted in a strong color aftereffect (Experiment 5). These results suggest that the color aftereffect contingent on text is very weak and is not dependent on semantic factors, but that it is a product of induction to local color and orientation information. PMID- 7984397 TI - Absolute memory for musical pitch: evidence from the production of learned melodies. AB - Evidence for the absolute nature of long-term auditory memory is provided by analyzing the production of familiar melodies. Additionally, a two-component theory of absolute pitch is presented, in which this rare ability is conceived as consisting of a more common ability, pitch memory, and a separate, less common ability, pitch labeling. Forty-six subjects sang two different popular songs, and their productions were compared with the actual pitches used in recordings of those songs. Forty percent of the subjects sang the correct pitch on at least one trial; 12% of the subjects hit the correct pitch on both trials, and 44% came within two semitones of the correct pitch on both trials. The results show a convergence with previous studies on the stability of auditory imagery and latent absolute pitch ability; the results further suggest that individuals might possess representations of pitch that are more stable and accurate than previously recognized. PMID- 7984398 TI - Interference in the perceived segregation of equal-luminance element-arrangement texture patterns. AB - Perceived segregation in element-arrangement patterns composed of squares of equal size and luminance, but of two different hues, was investigated in two experiments. Element-arrangement patterns consist of two types of elements, arranged in alternating vertical stripes in the top and bottom regions and in a checkerboard pattern in the center region. Perceived segregation of the striped and checkerboard regions decreased with increasing luminance of the interspaces between the squares, a high-luminance surround, and the increased spacing of the squares. When the luminance of the horizontal interspaces was increased, the decrease in perceived segregation was greater than that when the luminance of the vertical interspaces was increased. Two explanations of the interference of the interspace luminance are discussed. One explanation is in terms of inhibitory interactions among cortical filters tuned to spatial frequency and orientation. A second explanation is in terms of interference with preattentive grouping processes. PMID- 7984399 TI - Switching or sharing in dual-task line-length discrimination? AB - In two experiments, we tested whether subjects switched or shared attention between two simultaneously relevant line-length discrimination tasks. Switching models that allowed within- as well as between-trial switching were considered. In the first experiment, stimulus duration was varied randomly from trial to trial. With varied durations, many switching models predict negative contingencies: for a given duration and attentional allocation, accurate responses on one task should be associated with inaccurate responses on the other task. The results, however, showed no negative contingencies, which is consistent with sharing models. In the second experiment, stimulus duration was reduced to 20 msec, yet responses were more than 75% correct overall. This implies that information was obtained about both of the tasks within single trials, contradicting those switching models which predict that information can be obtained from, at most, one task within a period of 20 msec or less. In short, the results of both experiments support sharing models. PMID- 7984400 TI - The correlation of P-center adjustments with articulatory and acoustic events. AB - To evaluate articulatory models of perceptual center (P-center) location, listeners performed perceptual adjustments on stimuli which were extracted from a corpus of articulatory data. To avoid streaming effects, the stimuli were not edited to obtain temporal variation; instead, they varied in stress and segmental content. Adjustments were evaluated as to their simultaneity with acoustic and articulatory events. The first experiment yielded various articulatory and acoustic correlates of P-center location; the second yielded different articulatory predictors and no acoustic effective predictors. Multiple correlation analyses showed a variation from P-center locations predicted by the articulatory events that were associated with other predictors. Thus, P-center locations do not correspond to any particular kinematic articulatory event, but rather to a complex of events taken from throughout the stimuli. These results are discussed in terms of their relevance to a model of P-centers as indices of underlying gestural timing. PMID- 7984401 TI - Sensitivity to event timing in regular and irregular sequences: influences of musical skill. AB - In two experiments, the performance of listeners with different amounts of musical training (high skill, low skill) was examined in a two-alternative forced choice time-detection task involving simple five-cycle acoustic sequences. In each of a series of trials, all listeners determined which of two pattern cycles contained a small time change. Sequence context was also varied (regular vs. irregular timing). In Experiment 1, in which context was manipulated as a between subjects variable, high-skill listeners performed significantly better than low skill listeners only with regular patterns. In Experiment 2, in which context was manipulated as a within-subjects variable, the only significant source of variance was pattern context: All listeners were better at detecting time changes in regular than in irregular patterns. The results are considered in light of several hypotheses, including the expectancy/contrast model (Jones & Boltz, 1989). PMID- 7984402 TI - Frequency ratios and the discrimination of pure tone sequences. AB - We examined the effect of frequency ratios on the discrimination of patterns of alternating pure tones (ABABA). Listeners heard a repeating pattern presented in transposition (same frequency ratios between successive tones, different absolute frequencies) and were required to indicate when the pattern changed (different frequency ratios and absolute frequencies). Changes from patterns with simple frequency ratios to those with more complex ratios were more readily detected than were changes from complex ratios to simpler ratios. PMID- 7984403 TI - Behavioral estimates of interhemispheric transmission time and the signal detection method: a reappraisal. AB - On the basis of a review of the literature, Bashore (1981) concluded that only simple reaction time experiments with manual responses yielded consistent behavioral estimates of interhemispheric transmission time. A closer look at the data, however, revealed that these experiments were the only ones in which large numbers of observations were invariably obtained from many subjects. To investigate whether the methodological flaw was the origin of Bashore's conclusion, two experiments were run in which subjects had to react to lateralized light flashes. The first experiment dealt with manual reactions, the second with verbal reactions. Each experiment included a condition without catch trials (i.e., simple reaction time) and two conditions with catch trials. Catch trials were trials in which no stimulus was given and in which the response was to be withheld. Both experiments returned consistent estimates of interhemispheric transmission time in the range of 2-3 msec. No differences were found between the simple reaction time condition and the signal detection conditions with catch trials. Data were analyzed according to the variable criterion theory. This showed that the effect of catch trials, as well as the effect of interhemispheric transmission, was situated at the height of the detection criterion, and not in the rate of the information transmission. PMID- 7984404 TI - Nucleolar introns from Physarum flavicomum contain insertion elements that may explain how mobile group I introns gained their open reading frames. AB - Comparison of two group I intron sequences in the nucleolar genome of the myxomycete Physarum flavicomum to their homologs in the closely related Physarum polycephalum revealed insertion-like elements. One of the insertion-like elements consists of two repetitive sequence motifs of 11 and 101 bp in five and three copies, respectively. The smaller motif, which flanks the larger, resembles a target duplication and indicates a relationship to transposons or retroelements. The insertion-like elements are found in the peripheral loops of the RNA structure; the positions occupied by the ORFs of mobile nucleolar group I introns. The P. flavicomum introns are 1184 and 637 bp in size, located in the large subunit ribosomal RNA gene, and can be folded into group I intron structures at the RNA level. However, the intron 2s from both P. flavicomum and P. polycephalum contain an unusual core region that lacks the P8 segment. None of the introns are able to self-splice in vitro. Southern analysis of different isolates indicates that the introns are not optional in myxomycetes. PMID- 7984405 TI - DNA substrate specificity and cleavage kinetics of an archaeal homing-type endonuclease from Pyrobaculum organotrophum. AB - The protein encoded by intron 1 of the single 23S rRNA gene of the archaeal hyperthermophile Pyrobaculum organotrophum was isolated and shown to constitute a homing-type DNA endonuclease, I-PorI. It cleaves the intron- 23S rDNA of the closely related organism Pyrobaculum islandicum near the site of intron insertion in Pb.organotrophum. In contrast, no endonuclease activity was detected for the protein product of intron 2 of the same gene of Pb.organotrophum which, like I PorI, carries the LAGLI-DADG motif, common to group I intron-encoded homing enzymes. I-PorI cleaves optimally at 80 degrees C, with kcat and Km values of about 2 min-1 and 4 nM, respectively, and generates four nucleotide 3'-overhangs and 5'-phosphates. It can cleave a 25 base pair DNA fragment encompassing the intron insertion site. A mutation-selection study established the base pair specificity of the endonuclease within a 17 bp region, from positions -6 to +11 with respect to the intron-insertion site. Four of the essential base pairs encode the sequence involved in the intron-exon interaction in the pre-rRNA that is required for recognition by the RNA splicing enzymes. Properties of the enzyme are compared and contrasted with those of eucaryotic homing endonucleases. PMID- 7984406 TI - Target-specific arrest of mRNA translation by antisense 2'-O alkyloligoribonucleotides. AB - We describe a novel experimental approach to investigate mRNA translation. Antisense 2'-O-allyl oligoribonucleotides (oligos) efficiently arrest translation of targeted mRNAs in rabbit reticulocyte lysate and wheat germ extract while displaying minimal non-specific effects on translation. Oligo/mRNA-hybrids positioned anywhere within the 5' UTR or the first approximately 20 nucleotides of the open reading frame block cap-dependent translation initiation with high specificity. The thermodynamic stability of hybrids between 2'-O-alkyl oligos and RNA permits translational inhibition with oligos as short as 10 nucleotides. This inhibition is independent of RNase H cleavage or modifications which render the mRNA untranslatable. We show that 2'-O-alkyl oligos can also be employed to interfere with cap-independent internal initiation of translation and to arrest translation elongation. The latter is accomplished by UV-crosslinking of psoralen tagged 2'-O-methyloligoribonucleotides to the mRNA within the open reading frame. The utility of 2'-O-alkyloligoribonucleotides to arrest translation from defined positions within an mRNA provides new approaches to investigate mRNA translation. PMID- 7984407 TI - Heterogeneity in the 5' untranslated region of mouse cytochrome cT mRNAs leads to altered translational status of the mRNAs. AB - Previous studies have shown that the differential regulation of mouse somatic cytochrome c (cyt cS) and testicular cytochrome c (cyt cT) during spermatogenesis is accompanied by changes in mRNA length [Hake et al. (1990) Development, 110, 249-257]. When analyzed by polysomal gradient sedimentation, cytochrome cT sediments in two broad size classes: non-polysomal mRNAs are about 0.6 to 0.75 kb and polysomal mRNAs range from 0.7 to 0.9 kb. Both classes of mRNAs shorten to about 0.5 kb following deadenylation. Oligonucleotide-directed cleavage of the cytochrome cT RNAs by RNase H reveals that the size heterogeneity of cytochrome cT mRNAs resides in the 5' untranslated regions (UTRs). Ribonuclease protection assays reveal that multiple cytochrome cT mRNAs are transcribed from six different transcriptional start sites spanning a region of 59 nucleotides in the 5'UTR from +1 to +59. Transcripts derived from the first and second transcriptional initiation sites are not loaded onto polysomes as efficiently as those transcripts initiated from the other start sites. Each of the longer mRNAs has an upstream open reading frame, which starts at +8 and ends at +136 in the 5'UTR of the cytochrome cT transcript. Computer analysis suggests that the lengthened 5'UTR sequences allow additional hairpin structures to be formed. Since the upstream open reading frame and the additional stem loop structure are absent in the 5' UTRs of the cytochrome cT mRNAs initiated from the four downstream start sites, we suggest that these sequences in the two longest cytochrome cT transcripts hinder their loading onto polysomes. PMID- 7984408 TI - Different forms of U15 snoRNA are encoded in the introns of the ribosomal protein S1 gene of Xenopus laevis. AB - Recent cloning and sequencing of one of the two Xenopus gene copies (S1b) coding for the ribosomal protein S1 has revealed that its introns III, V and VI carry a region of about 150 nt that shares an identity of 60%. We show here the presence in Xenopus oocytes and cultured cells of a 143-147 nt long RNA species encoded by these three repeated sequences on the same strand as the S1 mRNA and by at least one repeat present in the S1 a copy of the r-protein gene. We identify these RNAs as forms of the small nucleolar RNA U15 (U15 snoRNA) because of their sequence homology with an already described human U15 RNA encoded in the first intron of the human r-protein S3 gene, which is homologous to Xenopus S1. Comparison of the various Xenopus and human U15 RNA forms shows a very high conservation in some regions, but considerable divergence in others. In particular the most conserved sequences include two box C and two box D motifs, typical of most snoRNAs interacting with the nucleolar protein fibrillarin. Adjacent to the two D boxes there are two sequences, 9 and 10 nt in length, which are perfectly complementary to an evolutionary conserved sequence of the 28S rRNA. Modeling the possible secondary structure of Xenopus and human U15 RNAs reveals that, in spite of the noticeable sequence diversity, a high structural conservation in some cases may be maintained by compensatory mutations. We show also that the different Xenopus U15 RNA forms are expressed at comparable levels, localized in the nucleoli and produced by processing of the intronic sequences, as recently described for other snoRNAs. PMID- 7984409 TI - Identification of a 59 bp enhancer located at the first exon/intron boundary of the human O6-methylguanine DNA methyltransferase gene. AB - The DNA repair enzyme, O6-methylguanine DNA methyltransferase (MGMT) is responsible for repair of damage induced by alkylating agents that produce adducts at O6-guanine in DNA. Although the MGMT gene promoter has housekeeping gene promoter characteristics, unlike these genes which are expressed at a constant level, MGMT transcriptional activity varies between cell types. During an attempt to identify regions of the MGMT regulatory sequence sensitive to variations in transcription factors between cell types, we have identified a 59 bp enhancer which is required for efficient MGMT promoter function. This fragment produced increased transcriptional activity in reporter gene constructs containing either the MGMT or UMP-synthase promoter when transfected into either of two cell lines; it seems therefore that this enhancer may interact with relatively common trans-acting factors. Functional activity is only detected when the enhancer is in 'cis' with respect to the promoter, suggesting that complexes are formed between proteins bound to the enhancer and promoter sequences. We propose that the enhancer-binding protein may be a novel transcription factor since there are no obvious consensus sequences within the 59 bp sequence for known DNA-binding proteins. PMID- 7984410 TI - Inhibition of gene-specific repair of alkylation damage in cells depleted of poly(ADP-ribose) polymerase. AB - The role of the enzyme poly(adenosine diphosphate-ribose) polymerase (PADPRP) in DNA repair at the level of the gene was investigated with human HeLa cells in which PADPRP antisense transcripts are inducible with dexamethasone. After such induction, the cellular content of PADPRP is reduced by 90%. DNA damage and its repair was studied in the essential dihydrofolate reductase (DHFR) gene after exposure of the cells to either ultraviolet (UV) irradiation or the alkylating agent nitrogen mustard. The expression of the antisense construct had no effect on gene-specific repair of UV-induced pyrimidine dimers. In contrast, induced antisense cells were deficient in the gene-specific repair of nitrogen mustard induced lesions. Dexamethasone itself did not inhibit gene-specific repair in control cells. Thus, PADPRP appears to participate in the gene-specific repair of alkylation damage, but not in the repair of UV-induced pyrimidine dimers. Clonal survival assays revealed that cells depleted of PADPRP showed an increased susceptibility to nitrogen mustard, supporting the notion that repair of essential genes is critical for cellular survival. PMID- 7984411 TI - Evidence for intramolecularly folded i-DNA structures in biologically relevant CCC-repeat sequences. AB - The structural behaviour of repetitive cytosine DNA is examined in the oligodeoxynucleotide sequences of (CCCTAA)3CCCT (HTC4), GC(TCCC)3TCCT(TCCC)3 (KRC6) and the methylated (CCCT)3TCCT(CCCT)3C (KRM6) by circular dichroism (CD), gel electrophoresis (PAGE), and ultra violet (UV) absorbance studies. All the three sequences exhibit a pH-induced cooperative structural transition as monitored by CD. An intense positive CD band around 285 nm develops on lowering the pH from 8 to slightly acidic condition, indicative of the formation of base pairs between protonated cytosines. The oligomers are found to melt in a fully reversible and cooperative fashion, with a melting temperature (Tm) of around 50 degrees C at pH 5.5. The melting temperatures are independent from DNA concentration, indicative of an intramolecular process involved in the structural formation. PAGE experiments performed with 32P-labeled samples as well as with normal staining procedures show a predominantly single band migration for all the three oligomers suggestive of a unimolecular structure. From pH titrations the number of protons required for generating the structures formed by HTC4, KRC6 and KRM6 results to be around six. These findings strongly suggest that all the three sequences adopt an intramolecular i-motif structure. The demonstration of i-motif structure for KRC6, a critical functional stretch of the c-ki-ras promoter proto oncogene, besides the human telomeric sequence HTC4, may be suggestive of larger significance in the functioning of DNA. PMID- 7984412 TI - Precise excision of the retrotransposon gypsy from the forked and cut loci in a genetically unstable D. melanogaster strain. AB - The genetically unstable Mutator Strain of D. melanogaster is characterised by a high frequency of spontaneous mutations and their reversions. Three forked mutants were obtained independently and several reversions arose spontaneously with frequency of 10(-3)-10(-4). The sites of integration and excision of the gypsy retrotransposon were analysed by Southern blot analysis and sequencing of PCR fragments. In all cases gypsy had inserted at the end of the third exon of the major transcript of the forked gene, causing the duplication of TCCA target sequence. All the reversions resulted from precise excision of the gypsy. A double mutant containing ct6 and f1, caused by gypsy insertions into untranslated regions of the corresponding genes, was constructed. Two spontaneous ct6f+ revertants as well as one ct+f1 revertant were obtained from this line. Sequence analysis of gypsy integration and excision sites revealed that in all cases gypsy excision was also precise. These experiments constitute the first demonstration of precise excision of LTR-containing elements from their host genomes. PMID- 7984413 TI - NMR evidence of the stabilisation by the carcinogen N-2-acetylaminofluorene of a frameshift mutagenesis intermediate. AB - Two heteroduplexes d(C1A2C3T4C5G6C7A8C9A10C11)-d (G12T13G14T15G16G17A18G19T20G21) containing a bulged guanine either unmodified or modified with the carcinogen N-2 acetylaminofluorene (AAF) have been studied by nuclear magnetic resonance (NMR) as models of slipped mutagenic intermediates (SMI). Conformational equilibria are observed in both the unmodified and the AAF-modified heteroduplexes. The major conformation of the unmodified duplex is one where the extra guanine is stacked in the helix and the major conformation of the AAF-modified heteroduplex is one where the AAF is external to the helix. Unusual sugar proton chemical shifts of C5- and G6-AAF indicate that the AAF ring is pointing out in the 5' direction. A strong increase in the modified heteroduplex melting temperature (+15 degrees C) is observed. Moreover, in contrast to the unmodified heteroduplex, which shows extensive melting in the vicinity of the bulged guanine, the base pairs around the bulge in the AAF-modified heteroduplex remain paired at temperatures up to 30 degrees C. This exceptional stability of the site around the bulged modified guanine is suggested to be responsible for the high rate of -1 mutation induced by AAF at repetitive sequences. PMID- 7984414 TI - Polycytosine regions contained in DNA hairpin loops interact via a four-stranded, parallel structure similar to the i-motif. AB - Thermal denaturation profiles of an oligodeoxynucleotide that forms a hairpin structure with a cytidine-rich loop show an unexpected transition at 60 degrees C at pH 5.0 but not at pH 8.0. Analytical ultracentrifugation shows that this transition reflects dimer formation via the interaction of loops from two molecules to form a novel structure termed the h-dimer. The dependence of this structure on low pH implies the formation of cytosine-protonated cytosine base pairs. NMR spectroscopy, thermal denaturation and ultraviolet absorption spectral analysis suggest a similarity to the i-motif structure recently proposed for the interaction of deoxycytidine oligomers. The use of hairpin loops to form i-motif like structures may prove useful in searches for cognate proteins and possibly in the production of antibodies. PMID- 7984415 TI - Changes in the stem-loop at the 3' terminus of histone mRNA affects its nucleocytoplasmic transport and cytoplasmic regulation. AB - The stem-loop structure at the 3' end of replication-dependent histone mRNA is required for efficient pre-mRNA processing, localization of histone mRNA to the polyribosomes, and regulation of histone mRNA degradation. A protein, the stem loop binding protein (SLBP), binds the 3' end of histone mRNA and is thought to mediate some or all of these processes. A mutant histone mRNA with two nucleotide changes in the loop was constructed and found to be transported inefficiently to the cytoplasm. The mutant histone mRNA, unlike the wild-type histone mRNA, was not rapidly degraded when DNA synthesis is inhibited, and was not stabilized upon inhibition of protein synthesis. The stem-loop binding protein (SLBP) has between a 20-50 fold greater affinity for the wild type histone stem-loop structure than for the mutant stem-loop structure, suggesting that the alteration in the efficiency of transport and the normal degradation pathway in histone mRNA may be due to the reduced affinity of the mutant stem-loop for the SLBP. PMID- 7984416 TI - Start site selection at lacUV5 promoter affected by the sequence context around the initiation sites. AB - The effects of single base pair substitutions at the initiation sites of lacUV5 promoter on the transcription start site selection by E. coli RNA polymerase were systematically studied. Transcription start sites were mapped by sizing the cytosine-specifically terminated transcripts produced in vitro by using a chain terminator 3'-deoxycytidine 5'-triphosphate (3'-dCTP) in transcription reactions. Transcription of a prototype lacUV5 promoter initiated with three purines (-1G, +1A and +2A; +1 representing the predominant start site) located 6-8 bp downstream from the Pribnow box. All the substitutions affected the start site selection, resulting in a change in the number of start sites (from 3 to 2 or 1) and/or a shift of the major start site (to -1 or +2). None of the variants started outside the 3-bp region and at the positions substituted by a pyrimidine. Purine-to-pyrimidine changes suppressed not only initiation at the substituted position but also, in some cases, at the other purine position. Purine-to-purine changes also shifted the major start site or suppressed the initiation at other sites. Changes at -2 and +5 also affected the start site selection. Thus, the sequence context around the initiation sites of lacUV5 promoter strongly influences the selection of initiating nucleotides by E. coli RNA polymerase. PMID- 7984417 TI - CLUSTAL W: improving the sensitivity of progressive multiple sequence alignment through sequence weighting, position-specific gap penalties and weight matrix choice. AB - The sensitivity of the commonly used progressive multiple sequence alignment method has been greatly improved for the alignment of divergent protein sequences. Firstly, individual weights are assigned to each sequence in a partial alignment in order to down-weight near-duplicate sequences and up-weight the most divergent ones. Secondly, amino acid substitution matrices are varied at different alignment stages according to the divergence of the sequences to be aligned. Thirdly, residue-specific gap penalties and locally reduced gap penalties in hydrophilic regions encourage new gaps in potential loop regions rather than regular secondary structure. Fourthly, positions in early alignments where gaps have been opened receive locally reduced gap penalties to encourage the opening up of new gaps at these positions. These modifications are incorporated into a new program, CLUSTAL W which is freely available. PMID- 7984418 TI - Improved biological activity of antisense oligonucleotides conjugated to a fusogenic peptide. AB - Recently several groups reported a dramatic improvement of reporter gene transfection efficiency using a fusogenic peptide, derived from the Influenza hemagglutinin envelop protein. This peptide changes conformation at acidic pH and destabilizes the endosomal membranes thus resulting in an increased cytoplasmic gene delivery. We describe the use of a similar fusogenic peptide in order to improve the antiviral potency of antisense oligodeoxynucleotides (anti TAT) and oligophosphorothioates (S-dC28) on de novo HIV infected CEM-SS lymphocytes in serum-free medium. We observed as 5 to 10 fold improvement of the anti HIV activities of the phosphodiester antisense oligonucleotides after chemical coupling to the peptide in a one to one ratio by a disulfide or thioether bond. No toxicities were observed at the effective doses (0.1-1 microM). No sequence specificity was obtained and the fusogenic peptide possessed some antiviral activities on its own (IC50: 6 microM). A S-dC28-peptide disulfide linked conjugate and a streptavidin-peptide-biotinylated S-dC28 adduct showed similar activities as the free S-dC28 oligonucleotide (IC50: 0.1-1 nM). As expected, all the compounds were less potent in the presence of serum but the relative contribution of peptide coupling was maintained. PMID- 7984419 TI - Transcriptional regulation of the apolipoprotein A-IV gene involves synergism between a proximal orphan receptor response element and a distant enhancer located in the upstream promoter region of the apolipoprotein C-III gene. AB - Apolipoprotein A-IV expression is limited to intestinal and hepatic cells, suggesting a tissue specific transcriptional regulation of its gene. To investigate the mechanism controlling apo A-IV transcription we have analysed its promoter region by in vitro DNA binding and transient transfection experiments. DNase I footprinting analysis of the proximal promoter with rat liver nuclear extracts revealed four protected regions: AIVA (-32 to -22), AIVB (-84 to -42), AIVC (-148 to -92) and AIVD (-274 to -250). Element AIVC which is necessary for maximal promoter activity, binds HNF-4, Arp-1 and Ear-3 with similar affinity in a mutually exclusive manner. HNF-4 transactivated chimeric constructs containing intact AIVC site in the context of either the apo A-IV promoter or the heterologous thymidine kinase minimal promoter, while Arp-1 and Ear-3 repressed this activation. Increasing amounts of HNF-4 alleviated Arp-1 or Ear-3 mediated repression, suggesting that the observed opposing effects is a result of direct competition of these factors for the same recognition site. In transient transfection assays the apo A-IV promoter region (-700 to +10) had a very low activity in cells of hepatic (HepG2) and intestinal (CaCo2) origin. This activity was increased 13 to 18-fold when the upstream elements of the distantly linked apo C-III gene were fused to the proximal promoter. Results obtained with different 5' and 3' deletion constructs indicated that the cis-acting elements F to J between the nucleotides -500 and -890 of the apo C-III promoter were absolutely necessary to drive maximal enhancement in HepG2 and CaCo2 cells. The apo C-III upstream elements enhanced the activity of the minimal AdML promoter or the apo A-IV site C mutant less efficiently than the intact apo A-IV or AdML promoter constructs containing single HNF-4 sites. The findings suggest that the enhancer effect is mediated by synergistic interactions between the trans-acting factors which recognize the apo C-III regulatory elements and HNF-4 which binds to the proximal apo A-IV promoter. PMID- 7984420 TI - Transcription of satellite 2 DNA from the newt is driven by a snRNA type of promoter. AB - The transcriptional promoter of satellite 2 from the eastern newt, Notophthalmus viridescens, was analyzed by assaying the activity of deleted or mutated satellite 2 clones in Xenopus laevis oocytes. Two elements in the promoter were found to be important for transcription. These elements have sequences that are similar to the sequences of the octamer and the proximal sequence element of vertebrate snRNA genes transcribed by RNA polymerase II. Furthermore, the organization of these elements and their respective roles in transcription are the same as their organization and roles in the snRNA genes. To further investigate the relationship between the satellite 2 and snRNA gene promoters, the ability of the satellite 2 promoter to drive transcription of a true snRNA gene was tested. The satellite 2 promoter initiated transcription of the Xenopus U1b2 snRNA gene as efficiently as the native U1b2 promoter, and the 3' ends of the resulting U1b2 transcripts were accurately formed. This latter result confirms that the satellite 2 promoter is a functional analog of the snRNA promoter, since 3'-end formation of snRNA genes transcribed by RNA polymerase II requires that transcription be initiated from a compatible promoter. The structural and functional similarities between the satellite 2 and the snRNA gene promoters suggest that these elements are evolutionarily related. These findings were used to extend a previously proposed model concerning the nature and derivation of satellite 2. PMID- 7984421 TI - Cooperative, non-specific binding of a zinc finger peptide to DNA. AB - The DNA binding and structural properties of Xfin-31 (Lee, M.S., Gippert, G.P., Soman, K.V., Case, D.A. and Wright, P.E., 1989, Science 245, 635-637), a twenty five amino acid zinc finger peptide, in the reduced, oxidized and zinc complex forms, as well as the fourteen residue helical segment of the zinc finger (residues 12-25) have been compared using affinity coelectrophoresis (ACE) and circular dichroism (CD) spectroscopy. The zinc complex and oxidized peptides bind cooperatively to DNA although the cooperativity factor, omega, is more than 15 fold greater for the zinc complex. The reduced peptide in the absence of zinc and the helical segment do not bind cooperatively (omega = 1). Hence, the binding constant for singly contiguous sites (K omega) ranges over 100-fold for the various peptides even though the intrinsic binding constants (K) are similar. An increase in binding order and affinity for the other forms of Xfin-31 is correlated with an increasing similarity of the CD spectrum to that of the Xfin 31 zinc complex. The surprising DNA binding activity of the oxidized peptide may result from hydrophobic interactions between the amino-terminal loop formed by the Cys3-Cys6 disulfide bond and conserved hydrophobic residues in the carboxyl terminal segment. Xfin-31 may be a particularly useful model for studying several poorly understood aspects of cooperative, non-specific DNA binding since it is small, has a stable, well-defined structure, and structures of zinc fingers bound to DNA have been determined. PMID- 7984422 TI - GAGA factor and TBF1 bind DNA elements that direct ubiquitous transcription of the Drosophila alpha 1-tubulin gene. AB - Three DNA regions (TE1, TE2 and the intron) regulate the ubiquitous expression of the alpha 1-tubulin gene of Drosophila melanogaster. In this report, we identify two proteins that bind these DNA regions. One is the previously characterized GAGA transcription factor and the other is a newly identified 62 kDa polypeptide, TBF1 (TE1-binding factor 1). Purified GAGA factor binds three sites in TE2 and at least three in the intron. TBF1 was purified from embryos and binds to both TE1 and TE2. Together, the two proteins produce the same DNase I footprints in TE1 and TE2 as does a nuclear extract that transcribes the gene accurately. These footprints cover most of the TE1 and TE2 DNA. Moreover, one binding site for each protein coincides with a site that activates transcription in vitro. The characteristics of the GAGA factor and the genes it regulates suggest roles these two proteins are likely to play in regulating ubiquitous expression. PMID- 7984423 TI - RNA-binding activities of the different domains of a spinach chloroplast ribonucleoprotein. AB - An RNA-binding protein of 28 kD (28RNP) has been previously isolated from spinach chloroplasts and was found to be required for 3' end processing of chloroplast mRNAs. The amino acid sequence of 28RNP revealed two approximately 80 amino-acid RNA-binding domains, as well as an acidic and glycine-rich amino terminal domain. Each domain by itself, as well as in combination with other domains, was expressed in bacterial cells and the polypeptides were purified to homogeneity. We have investigated the RNA-binding properties of the different structural domains using UV-crosslinking, saturation binding and competition between the different domains on RNA-binding. It was found that the acidic domain does not bind RNA, but that each of the RNA-binding domains, expressed either individually or together, do bind RNA, although with differing affinities. When either the first or second RNA-binding domain was coupled to the acidic domain, the affinity for RNA was greatly reduced. However, the acidic domain has a positive effect on the binding of the full-length protein to RNA, because the mature protein binds RNA with a better affinity than the truncated protein which lacks the acidic domain. In addition, it was found that a stretch of two or three G residues is enough to mediate binding of the 28RNP, whereas four U residues were insufficient. The implications of the RNA-binding properties of 28RNP to its possible function in the processing of chloroplast RNA is discussed. PMID- 7984424 TI - Rev of human immunodeficiency virus and Rex of the human T-cell leukemia virus type I can counteract an mRNA downregulatory element of the transferrin receptor mRNA. AB - Expression of the structural proteins of the human immunodeficiency virus type 1 (HIV-1), the human T-cell leukemia virus type I (HTLV-I), and of the transferrin receptor (TfR) mRNA depends on posttranscriptional regulatory mechanisms involving both positive and negative elements. In these systems the presence of elements decreasing mRNA expression have been demonstrated. The regulatory proteins (Rev, Rex or iron response element binding protein IRE-BP) antagonize the effects of the downregulatory elements by interacting directly with specific mRNA sites (Rev responsive element, RRE, Rex responsive element, RXRE, or iron responsive elements, IREs) resulting in stabilization and efficient expression of the corresponding mRNAs. To investigate whether this strategy involves common pathways of mRNA utilization, we have studied expression from hybrid mRNAs that contained these previously identified HIV-1 or TfR instability determinants and the binding sites of the regulatory proteins Rev, Rex and/or IRE-BP. Our results demonstrate that only low levels of these hybrid mRNAs accumulate in the absence of the positive regulatory factors Rev, Rex or IRE-BP. The presence of these factors counteracts the effect of heterologous downregulatory elements resulting in increased accumulation of the hybrid mRNAs. However, while Rev or Rex regulation also resulted in efficient protein expression, the IRE-BP only affected mRNA levels without significantly affecting protein expression, suggesting that the pathways of mRNA stabilization/expression are different in these systems. PMID- 7984425 TI - Alternative promoter usage and splicing options result in the differential expression of mRNAs encoding four isoforms of chicken VBP, a member of the PAR subfamily of bZIP transcription factors. AB - We previously isolated a set of overlapping cDNA clones that encoded a unique open reading frame for the chicken VBP transcription factor. We now report the isolation of a cDNA clone that encodes a complete open reading frame for a VBP isoform that differs from the previously reported sequence at both the amino terminal and carboxyl-terminal ends. An analysis of the VBP gene revealed that the two different amino-terminal sequences map to alternative first exons and that the two different carboxyl-terminal sequences reflect an optional splicing event which can occur only on transcripts that are polyadenylated at the more distal of two polyadenylation sites. An RT-PCR analysis further revealed that a total of four VBP isoforms are encoded by the combinatorial use of these two splicing options. The mRNAs for these four isoforms are differentially expressed in different tissues and cell types. We provide evidence that one function of the amino-terminal domains is to impose cell type specificity on a core transactivation domain that is present in all four isoforms. Since it is known that VBP can heterodimerize with other members of the PAR subfamily of bZIP factors, our evidence for four VBP isoforms greatly expands the number of complexes that may be used to effect transcriptional regulation through PAR factor binding sites. PMID- 7984426 TI - Oligodeoxyribonucleotide length and sequence effects on intermolecular purine purine-pyrimidine triple-helix formation. AB - The binding of guanosine/thymidine-rich oligodeoxyribonucleotides containing various deletions, extensions, and point mutations to polypurine DNA targets was investigated by DNase I footprinting. Intermolecular purine-purine-pyrimidine triple-helical DNA formation was best achieved using oligonucleotides 12 nucleotides in length. Longer oligonucleotides were slightly weaker in binding affinity, whereas shorter oligonucleotides were considerably weaker. Oligonucleotide extensions had a slight effect on triplex formation, while single point mutations located near the oligonucleotide ends had a greater effect. In the cases of extensions and point mutations, changes to the 3' end of the oligonucleotide had a consistently greater effect on triplex formation than changes to the 5' end. Such differences in triplex-forming ability were not caused by an intrinsic property of these oligonucleotides, since the same point mutated oligonucleotides could bind with high affinity to duplex DNAs containing complementary sites. Taken together, our data suggest that there may be an asymmetry involved in the process of purine-motif triplex formation, with interactions between the 3' end of the oligonucleotide and complementary sequences on the target duplex DNA being dominant. PMID- 7984427 TI - The presence of both negative and positive elements in the 5'-flanking sequence of the rat Na,K-ATPase alpha 3 subunit gene are required for brain expression in transgenic mice. AB - The Na,K-ATPase is an integral plasma membrane protein consisting of alpha and beta subunits, each of which has discrete isoforms expressed in a tissue-specific manner. Of the three functional alpha isoform genes, the one encoding the alpha 3 isoform is the most tissue-restricted in its expression, being found primarily in the brain. To identify regions of the alpha 3 isoform gene that are involved in directing expression in the brain, a 1.6 kb 5'-flanking sequence was attached to a reporter gene, chloramphenicol acetyltransferase (CAT). The alpha 3-CAT chimeric gene construct was microinjected into fertilized mouse eggs, and transgenic mice were produced. Analysis of adult transgenic mice from different lines revealed that the transgene is expressed primarily in the brain. To further delineate regions that are needed for conferring expression in this tissue, systematic deletions of the 5'-flanking sequence of the alpha 3-CAT fusion constructs were made and analyzed, again using transgenic mice. The results from these analyses indicate that DNA sequences required for mediating brain-specific expression of the alpha 3 isoform gene are present within 210 bp upstream of the transcription initiation site. alpha 3-CAT promoter constructs containing scanning mutations in this region were also assayed in transgenic mice. These studies have identified both a functional neural-restrictive silencer element as well as a positively acting cis element. PMID- 7984428 TI - Intrinsic and extrinsic approaches for detecting genes in a bacterial genome. AB - The unannotated regions of the Escherichia coli genome DNA sequence from the EcoSeq6 database, totaling 1,278 'intergenic' sequences of the combined length of 359,279 basepairs, were analyzed using computer-assisted methods with the aim of identifying putative unknown genes. The proposed strategy for finding new genes includes two key elements: i) prediction of expressed open reading frames (ORFs) using the GeneMark method based on Markov chain models for coding and non-coding regions of Escherichia coli DNA, and ii) search for protein sequence similarities using programs based on the BLAST algorithm and programs for motif identification. A total of 354 putative expressed ORFs were predicted by GeneMark. Using the BLASTX and TBLASTN programs, it was shown that 208 ORFs located in the unannotated regions of the E. coli chromosome are significantly similar to other protein sequences. Identification of 182 ORFs as probable genes was supported by GeneMark and BLAST, comprising 51.4% of the GeneMark 'hits' and 87.5% of the BLAST 'hits'. 73 putative new genes, comprising 20.6% of the GeneMark predictions, belong to ancient conserved protein families that include both eubacterial and eukaryotic members. This value is close to the overall proportion of highly conserved sequences among eubacterial proteins, indicating that the majority of the putative expressed ORFs that are predicted by GeneMark, but have no significant BLAST hits, nevertheless are likely to be real genes. The majority of the putative genes identified by BLAST search have been described since the release of the EcoSeq6 database, but about 70 genes have not been detected so far. Among these new identifications are genes encoding proteins with a variety of predicted functions including dehydrogenases, kinases, several other metabolic enzymes, ATPases, rRNA methyltransferases, membrane proteins, and different types of regulatory proteins. PMID- 7984429 TI - A hidden Markov model that finds genes in E. coli DNA. AB - A hidden Markov model (HMM) has been developed to find protein coding genes in E. coli DNA using E. coli genome DNA sequence from the EcoSeq6 database maintained by Kenn Rudd. This HMM includes states that model the codons and their frequencies in E. coli genes, as well as the patterns found in the intergenic region, including repetitive extragenic palindromic sequences and the Shine Delgarno motif. To account for potential sequencing errors and or frameshifts in raw genomic DNA sequence, it allows for the (very unlikely) possibility of insertions and deletions of individual nucleotides within a codon. The parameters of the HMM are estimated using approximately one million nucleotides of annotated DNA in EcoSeq6 and the model tested on a disjoint set of contigs containing about 325,000 nucleotides. The HMM finds the exact locations of about 80% of the known E. coli genes, and approximate locations for about 10%. It also finds several potentially new genes, and locates several places were insertion or deletion errors/and or frameshifts may be present in the contigs. PMID- 7984430 TI - Adenovirus 12-mediated down-regulation of the major histocompatibility complex (MHC) class I promoter: identification of a negative regulatory element responsive to Ad12 E1A. AB - In highly oncogenic adenovirus (Ad) 12-transformed cells, major histocompatibility complex (MHC) class I gene expression is down-regulated by the products of the viral E1A oncogene at the level of initiation of transcription. However, class I gene expression is unaltered or elevated in non-oncogenic Ad2- or Ad5-transformed cells. These changes in class I expression may permit Ad12 transformed cells to escape host immune surveillance and elicit tumour formation. Here we show that the 2kb of 5' flanking region of the mouse H-2Kb class I gene is sufficient to mediate down-regulation of transcription driven from homologous or heterologous (HSV thymidine kinase) basal promoter elements in cells expressing Ad12 E1A, but not in Ad2 E1A-expressing cells. Deletion analysis of the 2kb region showed that sequences from -1.18 to -1.44kb (relative to the cap site) were a target for Ad12 E1A-mediated transcriptional down-regulation. Deletion of this entire region from the 2kb flanking sequence of the H-2Kb gene abolished Ad12 E1A-mediated down-regulation of transcription. Computer analysis of the -1.18 to -1.44kb sequence identified two 6/7bp matches with the AP-1 transcription factor consensus sequence and two matches with the pig MHC class I PD1 repressor element. Gel retardation analysis using overlapping DNA fragments derived from the -1.18 to -1.44kb sequence revealed several DNA:protein complexes formed using nuclear extract derived from Ad12-, but not from Ad2- or Ad5 transformed cells. Some of these DNA:protein complexes were also present, but at lower levels, in nuclear extracts from untransformed rat cells suggesting the possible involvement of cellular factors in the mechanism of down-regulation mediated by Ad12 E1A. A binding site for the AP-1 factor failed to compete for protein binding to fragments within the -1.18 to -1.44 sequence, while the PD1 site competed for binding only in the -1.15 to -1.23 region. These results indicate that novel factors (as well as a previously identified class I repressor, PD1) may be involved in Ad12 E1A-mediated down-regulation of MHC class I transcription. PMID- 7984431 TI - Defining a novel ribonucleotide reductase r1 mRNA cis element that binds to an unique cytoplasmic trans-acting protein. AB - Ribonucleotide reductase is a highly regulated rate-limiting enzyme activity in DNA synthesis, responsible for reducing ribonucleotides to their deoxyribonucleotide forms. Using 3'-end labeled RNA and band-shift and UV cross linking analyses, we have identified a cis-element, 5'-CAAACUUC-3', within the 3' untranslated region of the mammalian ribonucleotide reductase R1 mRNA, which binds a cytoplasmic protein in BALB/c 3T3 mouse cells, to form a 57 kDa RNA protein complex. Sequence-specific binding was observed, and binding was prevented by several different mutations within the cis-element. We suggest that this cis-trans interaction plays a role in R1 mRNA stability. PMID- 7984433 TI - PCR-based immortalization and screening of hierarchical pools of cDNAs. AB - Starting from sequences of at least 60 bp, PCR-based screening has been developed to recover cDNAs from libraries without the necessity for hybridization or extensive DNA extraction steps. The method maintains the indefinite availability of even scarce cDNA libraries and provides an estimate of the relative abundance of the mRNA species. Isolation of a cDNA clone can be done in less than a week. cDNAs were isolated that were cognate for fragments of expressed sequences and for an exon predicted from genomic sequence. PMID- 7984432 TI - Sequence organization of the Acanthamoeba rRNA intergenic spacer: identification of transcriptional enhancers. AB - The primary sequence of the entire 2330 bp intergenic spacer of the A.castellanii ribosomal RNA gene was determined. Repeated sequence elements averaging 140 bp were identified and found to bind a protein required for optimum initiation at the core promoter. These repeated elements were shown to stimulate rRNA transcription by RNA polymerase I in vitro. The repeats inhibited transcription when placed in trans, and stimulated transcription when in cis, in either orientation, but only when upstream of the core promoter. Thus, these repeated elements have characteristics similar to polymerase I enhancers found in higher eukaryotes. The number of rRNA repeats in Acanthamoeba cells was determined to be 24 per haploid genome, the lowest number so far identified in any eukaryote. However, because Acanthamoeba is polyploid, each cell contains approximately 600 rRNA genes. PMID- 7984434 TI - Synthesis and properties of oligodeoxyribonucleotide-polyethylene glycol conjugates. AB - Pools of oligonucleotide conjugates consisting of 10-400 different molecular species were synthesized. The conjugates contained a varying number of ethylene glycol units attached to 3'-terminal, 5'-terminal and internal positions of the oligonucleotides. Conjugate synthesis was performed by phosphoramidite solid phase chemistry using suitably protected polyethylene glycol phosphoramidites and PEG-derivatized solid supports containing polydisperse PEGs of various molecular weight ranges. The pools were analyzed and fractionated by chromatographic and electrophoretic techniques, and the composition of isolated conjugates was revealed by matrix-assisted laser desorption/ionization mass spectrometry. The number and attachment sites of coupled ethylene glycol units greatly influence the hydrophobicity of the conjugates, as well as their electrophoretic mobilities. Conjugation had little effect on the hybridization behavior of oligonucleotide conjugates with unmodified complementary oligonucleotide strands. Melting temperatures were between 67 and 73 degrees C, depending on the size and number of coupled PEG chains, compared to 68 degrees C for the unmodified duplex. Conjugates with PEG coupled to both 3'- and 5'-terminal positions showed a more than 10-fold increase in exonuclease stability. PMID- 7984435 TI - Regulation of collagenase gene expression by IL-1 beta requires transcriptional and post-transcriptional mechanisms. AB - Interleukin-1 beta is believed to contribute to the pathophysiology of rheumatoid arthritis by activating collagenase gene expression. We have used a cell culture model of rabbit synovial fibroblasts to examine the molecular mechanisms of IL-1 beta-mediated collagenase gene expression. Stimulation of rabbit synovial fibroblasts with 10 ng/ml recombinant human IL-1 beta resulted in a 20-fold increase in collagenase mRNA by 12 h. Transient transfection studies using collagenase promoter-CAT constructs demonstrated that proximal sequences responded poorly to IL-1 beta, possibly due to insufficient activation of AP-1 by this cytokine. More distal sequences were required for IL-1 beta responsiveness, with a 4700 bp construct showing approximately 5-fold induction above control. To examine post-transcriptional mechanisms, transcript from a human collagenase cDNA was constitutively produced by the simian virus 40 early promoter. IL-1 beta stabilized the constitutively expressed human transcript. Furthermore, mutation of the ATTTA motifs in the 3' untranslated region of the human gene also stabilized the transcript. Finally, the rabbit collagenase 3' untranslated region destabilized a constitutively transcribed chloramphenicol acetyltransferase transcript. These data indicate that in addition to activating transcription, IL 1 beta increases collagenase transcript stability by reversing the destabilizing effects of sequences in the 3' untranslated region. PMID- 7984436 TI - A method for fast database search for all k-nucleotide repeats. AB - A significant portion of DNA consists of repeating patterns of various sizes, from very small (one, two and three nucleotides) to very large (over 300 nucleotides). Although the functions of these repeating regions are not well understood, they appear important for understanding the expression, regulation and evolution of DNA. For example, increases in the number of trinucleotide repeats have been associated with human genetic disease, including Fragile-X mental retardation and Huntington's disease. Repeats are also useful as a tool in mapping and identifying DNA; the number of copies of a particular pattern at a site is often variable among individuals (polymorphic) and is therefore helpful in locating genes via linkage studies and also in providing DNA fingerprints of individuals. The number of repeating regions is unknown as is the distribution of pattern sizes. It would be useful to search for such regions in the DNA database in order that they may be studied more fully. The DNA database currently consists of approximately 150 million basepairs and is growing exponentially. Therefore, any program to look for repeats must be efficient and fast. In this paper, we present some new techniques that are useful in recognizing repeating patterns and describe a new program for rapidly detecting repeat regions in the DNA database where the basic unit of the repeat has size up to 32 nucleotides. It is our hope that the examples in this paper will illustrate the unrealized diversity of repeats in DNA and that the program we have developed will be a useful tool for locating new and interesting repeats. PMID- 7984437 TI - Affinity capture-polymerase chain reaction for quantitation of hepatitis B virus DNA. PMID- 7984438 TI - A rapid, reliable method for detection of known point mutations: point-EXACCT. PMID- 7984439 TI - Simplified in vivo subcloning for easy handling of large sets of lambda ZAP clones. PMID- 7984440 TI - Direct neutralization of alkaline-denatured plasmid DNA in sequencing protocol by the sequencing reagent itself. PMID- 7984441 TI - Ligation-independent cloning of PCR products with primers containing nonbase residues. PMID- 7984442 TI - Guanine specific chemical sequencing of DNA by osmium tetroxide. PMID- 7984444 TI - The enemy within. PMID- 7984445 TI - Human and indirect costs of home care. PMID- 7984443 TI - Haemophilia A: database of nucleotide substitutions, deletions, insertions and rearrangements of the factor VIII gene, second edition. AB - A large number of different mutations in the factor VIII (F8) gene have been identified as a cause of haemophilia A. This compilation lists known single base pair substitutions, deletions and insertions in the F8 gene and reviews the status of the inversional events which account for a substantial proportion of mutations causing severe haemophilia A. PMID- 7984446 TI - Health promotion: a viable curriculum framework for nursing education. AB - Health care will be increasingly focused on the principles of health promotion and primary health care to better meet society's health needs. Nursing has an opportunity to lead the way in primary health care, however, for nurses to realize their potential, educational programs must be radically revised and be developed to teach nurses to work from a health-promotion perspective. Only when nurses have fully incorporated the principles of health promotion into their repertoire of working with clients and colleagues will they be the desired and appropriate profession to lead health care into the future. PMID- 7984447 TI - A health-promotion perspective of urinary continence. AB - The purposes of this article are to discuss continence in older adults from a public health perspective, to expand a previously reported conceptual model of continence health promotion, and to provide a primary prevention focus to nursing research efforts regarding continence. The conceptual model shows that there has been a strong interest in secondary and tertiary prevention strategies, but little interest in primary prevention. Use of the matrix allows the nurse researcher identify primary, secondary, or tertiary prevention research questions and the target population for study. Historically, nurses have had a central role in the care and management of incontinent people. Nurses will continue to play a critical role in the evolution of research-based practice that includes identification of risks, health promotion, and preventive nursing strategies. PMID- 7984448 TI - Required clinical course in gerontology: the key to providing competent nurse caregivers for the elderly. PMID- 7984449 TI - A survey of educators' activities to empower nurses for practice. PMID- 7984450 TI - Student satisfaction with classroom use of computer-assisted instruction. AB - In summary, the number of schools using CAI is increasing, and available CAI programs are multiplying rapidly. We believe that a critical factor in classroom use of CAI is the selection of appropriate topics for presentation by this method of media instruction. Faculty must know students' reactions and level of satisfaction with CAI to ensure that selection of this teaching methodology is made wisely, and that this methodology is an effective one for the student. Therefore students must be included in the process of evaluating media instruction. PMID- 7984451 TI - Ethical issues in nursing children with HIV. PMID- 7984452 TI - Child sex abuse exclusive report. Benefit of hindsight. PMID- 7984453 TI - Laboratory practice. PMID- 7984454 TI - Private notions. PMID- 7984455 TI - Quality of life of patients with oesophageal carcinoma. AB - 'Quality of life' is a concept of central importance in oncology nursing. This paper discusses a nurse-led audit of the quality of life experienced by patients with oesophageal cancer, and what is hoped to be achieved by it. PMID- 7984456 TI - Detecting colorectal cancer. AB - Although colorectal cancer affects up to 28,000 people in the UK each year, and early detection is associated with a high cure rate, little exists in the way of health promotional literature dealing with the subject. This paper looks at what is needed to make initiatives in this area more useful. PMID- 7984457 TI - BCG in bladder cancer. AB - BCG is usually thought of as a vaccine for tuberculosis. This paper describes how it can be used as an alternative to cytotoxic agents in the treatment of bladder cancer. PMID- 7984458 TI - Working with the health promotion banding scheme. AB - This paper outlines the main health promotion requirements imposed on general practice through the banding programmes. The author describes the role of practice nurses in the delivery of this care and evaluates the effectiveness of the programmes a year on from their introduction. PMID- 7984459 TI - Health promotion. Cervical screening update. AB - Strategies to attract women who have never had, or are long overdue to have, smear tests are explained in this article. The author suggests that refusal to have a smear taken must be an informed decision and that the right to refuse must be respected. PMID- 7984460 TI - Sensitivity and care: vital tools for skill-mix review. AB - The issue of skill mix has become linked in the minds of many nurses with 'skill dilution'. This paper discusses the ideas used in a skill-mix review and looks at the essential differences between skill mix and grade mix. The authors have examined the literature and draw some important lessons, providing pointers for anybody who is charged with, or whose unit is subject to, a skill-mix review. PMID- 7984461 TI - Nurses' attitudes towards management of pain. AB - This research was carried out to discover nurses' attitudes towards and perceptions of post-operative pain management; knowledge of pain assessment; awareness of different methods of pain relief; and view of the necessity for education in post-operative pain management. The major findings of the research correlated with the authors' observations while undertaking audit. That is, that there is a need for conformity of pain assessment and pain scoring. It also showed a need for a focused education programme in postoperative pain management. PMID- 7984462 TI - Promoting the integration of primary care and public health. AB - This fourth paper in our health promotion examines how primary health-care nurses' position at the interface between lay and professional care makes them well placed to influence public health-care policy within the new culture of the NHS. PMID- 7984463 TI - Hospital security. Criminal tendencies. PMID- 7984464 TI - Spirited accounts. PMID- 7984465 TI - Pregnant clauses. PMID- 7984466 TI - Continence. Setting standards. PMID- 7984467 TI - Continence. Achieving good care. PMID- 7984468 TI - Continence. Indwelling urinary catheters. PMID- 7984469 TI - Continence. The tyranny of interstitial cystitis. PMID- 7984470 TI - Continence. Time for action. PMID- 7984471 TI - Professional development. Promoting continence: knowledge for practice (continuing education credit). PMID- 7984472 TI - A lifetime of opportunity? PMID- 7984473 TI - Human response. Interview by Ian McMillan. PMID- 7984474 TI - A study in overwork. Interview by Paul Mangan. PMID- 7984475 TI - Nurses must take lead on HIV care. PMID- 7984476 TI - Healing. Hands-on help. PMID- 7984477 TI - Healing. Keeping in touch. PMID- 7984478 TI - Healing. Centre of balance. Interview by Irene Heywood Jones. PMID- 7984479 TI - Making sense of peak-flow recordings of lung function. PMID- 7984480 TI - Developing an early pregnancy assessment unit. AB - This paper describes the work of a nurse-run early pregnancy assessment service in Sheffield. The authors explain how the unit attempts to reduce the anxieties of women who may be prone to miscarriage by screening them early and offering same-day results. PMID- 7984481 TI - Causes and management of nausea and vomiting. AB - Nausea and vomiting affect large numbers of patients in hospital for a variety of reasons. This paper summarises possible causes, looks at the pharmaceutical methods of management and their modes of action, and concludes with an examination of nursing implications. PMID- 7984482 TI - Effective communication with people with visual disabilities. AB - A little-considered element of visual disability is its impact on communication. This paper discusses ways in which health-care professionals can adapt verbal and non-verbal communication techniques to make nurse/patient interaction more productive. PMID- 7984484 TI - Activating the activists. PMID- 7984483 TI - Hidden dilemma. PMID- 7984485 TI - Private functions. PMID- 7984486 TI - An analysis of critical incidents describing the essence of oncology nursing. AB - PURPOSE: To describe oncology nurses' perceptions of the meaning of their work using particularly relevant anecdotes. DESIGN: Multi-institutional, descriptive, qualitative. SETTING: Six sites in different regions of the United States; rural and urban cancer and noncancer centers. SAMPLE: 38 oncology nurses (mean age = 35 years; average time in nursing = 10 years and in oncology = 7 years; 47% bachelor's degrees in nursing, 29% diploma, 13% associate degree in nursing, and 11% master's prepared). METHODS: Phenomenological; content analysis of interviews. FINDINGS: Nurses described three roles, each characterized by a set of activities: (a) maintaining the values of the healthcare establishment as characterized by monitoring, acting on patients' behalf, protecting patients, and bringing patients into line, (b) participating in patients' experiences as characterized by "being there" for patients, being with dying patients, and, in a sense, becoming part of patients' families, and (c) reconciling healthcare values and the experiences of patients as characterized by teaching and telling the truth. CONCLUSIONS: Nurses not only demonstrated self-confidence, courage, emotional strength, and a desire to be empathetic but also displayed an unexamined belief that they understood their patients' experiences, were isolated in their work, and experienced difficulty dealing with suffering. IMPLICATIONS FOR NURSING PRACTICE: Future research should establish whether nurses' understanding of their patients' experiences correlates with patients' accounts of those experiences and whether nurses' sense of isolation is indicative of a pattern of inadequate supportive resources. PMID- 7984487 TI - Cultivating expertise in oncology nursing: methods, mentors, and memories. AB - PURPOSE: To explore the development of clinical expertise and the role of mentoring experiences in this process for oncology nurses involved in direct patient care. DESIGN: Multi-institutional, descriptive, qualitative. SETTING: Six sites in different regions of the United States; rural and urban cancer and noncancer centers. SAMPLE: 38 oncology nurses (mean age = 35 years; average time in nursing = 10 years and in oncology = 7 years; 47% bachelor of science in nursing, 29% diploma, 13% associate degree in nursing, and 11% master's prepared). METHODS: Phenomenological; content analysis of interviews. FINDINGS: Development of clinical expertise and professional commitment requires a combination of protegee- and mentor-initiated behaviors. Protegee learning included reading, watching, attending, doing, asking questions, seeking peer support, seeking new opportunities, and associating with others. Mentor contributions included modeling standards and beliefs, coping effectively, explaining knowledge, and believing in, challenging, and supporting the protegee personally and professionally. The absence of mentoring also was of concern to nurses. True mentoring required on interpersonal connection and commitment between the protegee and mentor. IMPLICATIONS FOR NURSING PRACTICE: Mentoring enhances the development of expert nurses who combine competent clinical practice with strong interpersonal commitment to their patients and the oncology nursing profession. The benefits of mentoring outcomes for individual oncology nurses, their patients, the institutional setting, and the profession need further exploration, especially given the focus on advanced practice and healthcare reform. PMID- 7984488 TI - The atypical becomes typical: the work of oncology nurses. AB - PURPOSE: To describe a typical day for nurses who work with patients with cancer. DESIGN: Multi-institutional, descriptive, qualitative. SETTING: Six sites in different regions of the United States; rural and urban cancer and noncancer centers. SAMPLE: 38 oncology nurses (mean age = 35 years; average time in nursing = 10 years; and in oncology = 7 years; 47% bachelor of science in nursing, 29% diploma, 13% associate degree in nursing, and 11% master's prepared. METHODS: Phenomenological; content analysis of interviews. FINDINGS: There is no typical day for oncology nurses. As such, the atypical becomes typical. This dialectic influenced how the nurses organized and managed their work. Management became a paradox or a juggling act--an attempt to control the uncontrollable, to manage the unmanageable. Time was a central metaphor used in the descriptions. The amount of time available influenced nurses' abilities to perform a certain quality and quantity of work. Demands on time, whether legitimate or illegitimate, were the context for the day-to-day work. IMPLICATIONS FOR NURSING PRACTICE: It is necessary to recognize the value that nurses continually place on participation in patients' daily care, the unpredictability inherent in cancer and patient care, and the organizational routines that nurses use to accomplish their work. PMID- 7984489 TI - What makes oncology nursing special? Walking the road together. AB - PURPOSE: To identify the factors that influence oncology nurses' decisions to enter nursing and specialize in oncology and to describe the role dimensions of oncology nursing practice. DESIGN: Multi-institutional, descriptive, qualitative. SETTING: Six sites in different regions of the United States; rural and urban cancer and noncancer centers. SAMPLE: 38 oncology nurses (mean age = 35 years; average time in nursing = 10 years and in oncology = 7 years; 47% bachelor's degree in nursing, 29% diploma, 13% associate degree in nursing, and 11% master's prepared). METHODS: Phenomenological; content analysis of interviews. MAIN RESEARCH VARIABLES: Life events, career decision-making, personal and professional rewards, role dimensions of practice, caring behaviors. FINDINGS: Nurses said that their decisions to specialize in oncology were based on family experiences with cancer, the challenges of administering sophisticated cancer therapies, and influential role models. They reported that professional rewards are derived from valuing each patients as a 'whole person' and providing family centered care. Nurses find that personal rewards and career survivorship are embedded in several ongoing discoveries: work offers a unique laboratory for learning about life in general, distancing maneuvers are necessary for self preservation, and the fuzzy boundary between work and personal life must be constantly renegotiated. CONCLUSIONS: Oncology nurses find the best in the worst of situations, live fully the cancer experience by embracing their patients' heartaches and triumphs, share a collective sense of pride in their specialty, and report a high level of job satisfaction. IMPLICATIONS FOR NURSING PRACTICE: Caring for the dying person with cancer is the most difficult aspect of oncology nursing practice and being with--being present in the moment, no matter what the outcome--is the most rewarding and ubiquitous caring behavior of oncology nurses. PMID- 7984490 TI - The meaning of oncology nursing: a phenomenological investigation. AB - PURPOSE: To describe the method used in a multisite study of the meaning of oncology nursing from the oncology nurses' perspectives. DESIGN: Multi institutional, descriptive, qualitative. SETTING: Six sites in different regions of the United States; rural and urban cancer and noncancer centers. SAMPLE: 38 oncology nurses (mean age = 35 years; average time in nursing = 10 years and in oncology = 7 years; 47% bachelor's degree in nursing, 29% diploma, 13% associate degree in nursing, and 11% master's prepared). METHODS: Phenomenological; content analysis of interviews. FINDINGS: Nurses' experiences in caring for people with cancer have many similarities despite the differences among these nurses or their work settings. These similarities are described in this supplement. IMPLICATIONS FOR NURSING PRACTICE: Many nurses said they had not described their experiences to interested listeners before. Providing these descriptions helped the nurses to see their work in new ways and led some of them to make changes in their personal and professional lives. PMID- 7984491 TI - Rewards and difficulties of oncology nursing. AB - PURPOSE: To describe oncology nurses' perceptions of the rewards and difficulties of their work. DESIGN: Multi-institutional, descriptive, qualitative. SETTING: Six sites in different regions of the United States; rural and urban cancer and noncancer centers. SAMPLE: 38 oncology nurses (mean age = 35 years; average time in nursing = 10 years and in oncology = 7 years; 47% bachelor's degree in nursing, 29% diploma, 13% associate degree in nursing, and 11% master's prepared). METHODS: Phenomenological; content analysis of interviews. FINDINGS: Nurses described sources and origins of both job stress and satisfaction. The three most important sources of rewards were patients, co-workers, and new skills. These sources of rewards also were described as sources of difficulties. Additional sources of difficulties include lack of competent administrators, lack of time, and life stresses. IMPLICATIONS FOR NURSING PRACTICE: Nurses' experiences with work are shaped by both common and very individual and personal realities. Aspects that are rewarding also are difficult, and individual experiences and perceptions change the meaning of work and the needs that nurses have. Considering the findings in the context of nurses' lives may yield more fruitful approaches to providing support and resources that nurses need to be able to provide effective care for patients and their families. PMID- 7984492 TI - Callitachykinin I and II, two novel myotropic peptides isolated from the blowfly, Calliphora vomitoria, that have resemblances to tachykinins. AB - Two peptides, related to the locust myotropic peptides locustatachykinin I-IV, were isolated from the blowfly Calliphora vomitoria. Whole, frozen flies were used for extraction with acidified methanol. A cockroach hindgut muscle contraction bioassay was used for monitoring fractions during subsequent purification steps. A series of eight different high performance liquid chromatography column systems was required to obtain optically pure peptides. Two peptides were isolated and their sequences determined by Edman degradation and confirmed by mass spectrometry and chemical synthesis as APTAFYGVR-NH2 and GLGNNAFVGVR-NH2. They were named callitachykinin I and II. The peptides have sequence similarities to the locustatachykinins and vertebrate tachykinins. Both callitachykinins were recognized by an antiserum to locustatachykinin I in enzyme linked immunosorbent assay (ELISA) tests and callitachykinin II was additionally recognized by an antiserum to the vertebrate tachykinin kassinin, suggesting that immunolabeling of blowfly neurons with these antisera is due to neuronal callitachykinins. PMID- 7984493 TI - Beta-endorphin content in HIV-infected HuT78 cell line and in peripheral lymphocytes from HIV-positive subjects. AB - We investigated beta-endorphin (BE) content in an HIV-infected cell line and in peripheral blood mononuclear cells (PBM) from HIV-positive subjects. HIV infection increased BE content in HuT78 cell line compared to uninfected cells. Accordingly, BE content was greater in HIV-positive subjects than in healthy controls, both in fresh PBM and in mitogen-stimulated or unstimulated cultured cells. Further, in PHA-stimulated cultures, BE increase was correlated with disease progression. Opioids are known to decrease immune responsiveness in vivo, and it may be that the increased BE concentrations contribute to HIV-associated immune deficiency. In HIV-positive subjects, but not in healthy controls, intracellular BE concentration was positively correlated with PHA-induced PBM proliferation. The latter data suggest an alternative explanation: that the increased BE content represents a paradoxical response of the host in an attempt to balance virus-induced immunodepression. Thus, BE may be important in fine tuning of the immune response with its up- and downregulation dependent upon differences in immune status. PMID- 7984494 TI - The prothoracicotropic hormone (PTTH) of the commercial silkmoth, Bombyx mori, in the CNS of the tobacco hornworm, Manduca sexta. AB - Immunocytochemistry revealed that a Bombyx mori prothoracicotropic hormone (PTTH) like peptide is expressed by the Manduca sexta big PTTH-producing neurons, the lateral neurosecretory cell group III (L-NSC III). Independent PCR of genomic DNA and a L-NSC III cDNA library yielded products with 99% sequence similarity to the cDNA encoding Bombyx PTTH. This similarity necessitated evaluation of the relationship between Manduca big PTTH and Bombyx PTTH by 1) bioassay of IEF separated Manduca PTTH and 2) direct assessment of Bombyx PTTH biological activity with Manduca prothoracic glands. Together, these studies indicate that Bombyx PTTH and Manduca PTTH are different peptides expressed by the L-NSC III. The possible physiological significance of a Bombyx PTTH-like peptide in Manduca and its coexpression with Manduca big PTTH by the L-NSC III are discussed. PMID- 7984495 TI - Effect of acute stress on the expression of hypothalamic messenger ribonucleic acids encoding the endogenous opioid precursors preproenkephalin A and proopiomelanocortin. AB - In addition to the release of adenohypophysial hormones adrenocorticotropin and beta-endorphin, most types of acute stress induce rapid release of prolactin (PRL) from the anterior pituitary lobe. Endogenous opioid peptides are believed to participate in the stress-induced PRL secretion via an action within the central nervous system. In the present study, we have investigated the effect of acute stress on anterior pituitary PRL secretion and the hypothalamic expression of messenger ribonucleic acids (mRNAs) encoding precursors of the endogenous opioids Met-enkephalin and beta-endorphin. Adult male rats were subjected to 1 h of restraint and the stress-induced rise in plasma PRL was measured both during and after termination of the stress paradigm. Using quantitative in situ hybridization histochemistry, it was observed that levels of proenkephalin A mRNA increased significantly within the medial parvocellular subset of the hypothalamic paraventricular nucleus, and within the arcuate nucleus levels of proopiomelanocortin (POMC) mRNA were slightly, but significantly, increased. The employed stress paradigm also induced an elevation of anterior pituitary levels of PRL and POMC mRNAs. The present data suggest that restraint stress activates gene expression of endogenous opioid systems in the hypothalamus and that the employed stress paradigm is of sufficient magnitude to stimulate both mRNA expression and release of PRL in the anterior pituitary lobe. PMID- 7984496 TI - Lymphoid cell subpopulations containing vasoactive intestinal peptide in the rat. AB - In the present study we describe the cell types containing immunoreactive vasoactive intestinal peptide (IR-VIP) in rat thymus, spleen, and lymph nodes. Indirect immunofluorescence staining and flow cytometry indicated that all lymphoid organs studied contained VIP-positive cells, with the spleen and lymph nodes having a higher proportion than the thymus. Vasoactive intestinal peptide was found in both lymphocytes and nonlymphoid cells, lymphocytes predominating among VIP-positive cells. Double immunofluorescent staining and flow cytometry showed that all lymphoid subpopulations identified contained variable proportions of VIP-positive lymphocytes. Immunocytochemical staining of cell suspensions for both light and electron microscopy showed the cytoplasmic localization of the IR VIP. These findings, coupled to our previous results, are consistent with the idea that VIP may have a lymphoid origin and could be active in local immune responses. PMID- 7984497 TI - In vivo central actions of NPY(1-30), an N-terminal fragment of neuropeptide Y. AB - The purpose of the present study was to examine the possible central actions of a N-terminal fragment of NPY, NPY(1-30), on five measures typically influenced by the native peptide: decreased spontaneous activity, enhancement of muscle tone (increased grasping response), catalepsy, hypothermia, and stimulation of food intake. The peptides were administered ICV in doses ranging from 2.5 to 160 micrograms (0.75-48 nmol) and their effects on the three motor variables as well as thermal and feeding responses were evaluated and compared. Globally, results indicate that, similarly to NPY, the N-terminal fragment NPY(1-30), decreased spontaneous activity and induced hypothermia. However, the fragment displayed approximately half of the potency of NPY for producing these effects. On the other hand, contrary to NPY, NPY(1-30) did not affect muscle tone or food consumption and did not induced catalepsy in animals. These results demonstrate for the first time central actions of a N-terminal fragment of NPY and lend further support to the hypothesis that the receptors mediating the central actions of NPY are pharmacologically different. PMID- 7984498 TI - Gastrointestinal absorption and plasma clearance rates of [D-Arg8]vasopressin analogues in the rat. AB - The gastrointestinal absorption of a series of vasopressin (VP) analogues with enhanced enzymatic stability was determined in chronically catheterized, conscious rats. The following peptides were used: [Mpa1,D-Arg8]vasopressin (dDAVP), [Mpa1,Asn4,D-Arg8]VP, [Mpa1,Val4,D-Arg8]VP, [Mpa1,(CH3)3Ala4,D-Arg8]VP, [Mpa1,Tyr(ethyl)2,D-Arg8]VP, and [Mpa1,D-Tyr(ethyl)2,Ile3,Val4,D-Arg8]VP. The peptides were administered by gavage feeding and blood samples were taken repeatedly for 3 h. In another series of experiments, plasma clearance rates (Clp) were determined using the constant infusion method. Plasma concentrations were measured by use of a cross-reacting dDAVP antiserum in a radioimmunoassay method. The bioavailability of all peptides was below 0.1%. The Clp values differed sevenfold; the lowest was for [Mpa1,D-Tyr(ethyl)2,Ile3,Val4,D-Arg8]VP and the highest was for [Mpa1,Asn4,D-Arg8]VP. With the exception of dDAVP the Clp values of the analogues showed an inverse relationship with hydrophilicity. Incubations in relatively concentrated intestinal contents for 1 h showed extensive degradation of the analogues except for [Mpa1,D-Tyr(ethyl)2,Ile3,Val4,D Arg8]VP. It can be concluded that, in the rat, the bioavailability of dDAVP is lower than in other animal species and in man. Increased resistance to peptide degradation by gastrointestinal contents did not improve absorption. Therefore, the permeability properties of the intestinal mucosa are likely to be a more important factor affecting the gastrointestinal absorption of this group of peptides, although postabsorption events, like hepatic extraction, may also play a role. PMID- 7984499 TI - Characterization of two forms of peptide YY, PYY(1-36) and PYY(3-36), in the rabbit. AB - Peptide YY (PYY) has been purified as a 36 amino acid peptide from intestinal extracts of several mammalian species including pig, rat, dog, and man. The primary structure of rabbit PYY is still unknown, although rabbit tissues have extensively been used for characterization of PYY receptor subtypes and receptor subtype-mediated actions. We report the purification and primary structure of PYY(1-36) (PYY-I) from rabbit intestinal mucosa, and the existence of a second endogenous molecular form of PYY, PYY(3-36) (PYY-II). The amino acid sequence of PYY-I is YPSKPEAPGEDASPEELNRYYASLRHYLNLVTRQRY-amide. Rabbit PYY differs from porcine PYY, which is identical to rat and canine PYY, by two amino acid substitutions at positions 3 (Ser instead of Ala) and 18 (Asp instead of Ser), whereas rabbit PYY and human PYY differ by only one residue at position 3 (Ser instead of Ile). The existence of two endogenous forms of PYY in the rabbit, with PYY-II lacking the amino-terminal dipeptide Tyr-Pro of PYY-I, is consistent with previously reported findings, demonstrating the existence of PYY-II in man and dog (9,11). We have previously demonstrated that PYY-I is an unselective Y1/Y2 agonist, whereas PYY-II is a highly selective Y2 agonist. Thus, proteolytic processing of PYY-I controls the peptide's receptor selectivity. The existence of PYY-I and PYY-II in the rabbit supports the assumption of a physiological role of Y receptor heterogeneity for PYY. PMID- 7984500 TI - Autoradiographic localization and characterization of angiotensin II receptor subtypes in the rat thymus. AB - Angiotensin II (ANG II) receptors were present in the thymus of newborn rats (179 +/- 34 fmol/mg protein). In newborns, binding was predominantly localized in the trabecula, and was selectively displaced by the AT2 ligand CGP 42112A (83-85%) and to a lower extent by the AT1 antagonist losartan (15-17%), indicating a marked predominance of AT2 receptors. Angiotensin II binding was very low in the cortical and medullary areas in the thymus of newborn rats and was no longer detected in the thymus of 4- and 8-week-old rats. No detectable binding for the ACE inhibitor [125I]351A was observed in the thymus of the rat, regardless of the age studied. Our results indicate a possible role for circulating ANG II during development of the thymus with no clear correlation to lymphocyte maturation. PMID- 7984501 TI - Biosynthesis of growth hormone-releasing factor by fetal rat cerebrocortical and hypothalamic cells. AB - The biosynthesis of growth hormone-releasing factor (GRF) by cerebrocortical tissue is controversial. Although several reports have indicated its presence in certain rat cortical areas and in cultured rat hypothalamic cells, no data exist demonstrating its biosynthesis in these areas. In this study, we have investigated the capacity of fetal rat cerebrocortical and hypothalamic cells in culture for synthesizing GRF. Fetal cerebrocortical and hypothalamic cells were exposed to [3H]Arg for 48 h. Medium and cell extracts were processed and [3H]Arg IR-rGRF was isolated by affinity chromatography and characterized by HPLC. Intracellular [3H]Arg-IR-rGRF from both hypothalamic and cerebrocortical cells exhibited four major peaks, one of them coeluting with synthetic rGRF. In cerebrocortical cultures, newly synthesized and released [3H]Arg-IR-rGRF showed a similar pattern to the cell content. However, in media from hypothalamic cells, higher hydrophobicity molecular forms were absent. The data demonstrated that fetal cerebrocortical and hypothalamic cells in primary culture synthesize GRF with similar posttranslational processing, but with different molecular patterns of secretion. PMID- 7984502 TI - Coupling an alpha 2-adrenergic receptor peptide to G-protein: a new photolabeling agent. AB - A photoreactive derivative of a tetradecapeptide G-protein activator (peptide Q) derived from the alpha 2-adrenergic receptor was designed and used to label purified G-protein (Go/Gi). N-bromoacetyl-N'-(3-diazopyruvoyl)-m-phenylene diamine (Br-DAP) was conjugated to the C-terminal cysteine of peptide Q. The DAP modified peptide Q (DAP-Q) specifically incorporated into the a subunit of Go. The incorporation of DAP-Q into alpha o was blocked by unmodified Q peptide (IC50 = 15 +/- 6 microM; n = 4). Photolysis of sixfold higher concentrations of DAP-Q with ovalbumin or bovine albumin failed to produce cross-linked products. Br-DAP should prove useful in detecting mutual contact sites between peptides and their binding proteins. PMID- 7984503 TI - Biological activity and receptor binding properties of some analogues of pQDPFLRFamide. AB - To investigate the role of the N-terminal region of the heptapeptide FMRFamide like peptide, pQDPFLRFamide, three analogues were synthesized. The analogues [pQNPFLRFamide, pQDAibFLRFamide (Aib = aminoisobutyric acid) and pQDGFLRFamide] contained modifications at amino acid residues 2 and 3, which we believed might be critical for maintaining the bioactive conformation of the heptapeptide. The analogues were tested for their ability to bind to receptors in membranes from Helix aspersa circumoesophageal ganglia and for their biological effects on the isolated Helix heart, the Helix tentacle retractor muscle, and extensor-tibiae neuromuscular preparation of the locust. Schistocerca gregaria. The substitution of Asn for Asp2 and that of Aib for Pro3 were conservative with respect to retention of heptapeptide-like biological activity, whereas the substitution of Gly for Pro3 significantly improved the binding affinity of the peptide for the FMRFamide receptors and conferred on the peptide some characteristic FMRFamide like biological activity. Thus, pQDPFLRFamide bioactivity may depend on a bent conformation in solution. PMID- 7984504 TI - Structural requirements for the biological activity of enterostatin. AB - A series of enterostatin analogues were tested to investigate the minimal structure required for activity to suppress the intake of high-fat (HF) diets. The dose-response curve to intracerebroventricular (ICV) enterostatin was U shaped (maximal inhibition at 1 nmol). Removal or modification of the N-terminal valine from enterostatin (Val-Pro-Asp-Pro-Arg) abolished activity, as did C terminal amidation. The tripeptide (Pro-Asp-Pro) and the cyclo-diketopiperazine cyclo-Asp-Pro retained activity whereas the linear Asp-Pro dipeptide was inactive. In rats adapted to a three-choice macronutrient diet, cyclo-Asp-Pro specifically inhibited fat intake and had near maximal inhibition (50%) at the 0.03 nmol dose. The enterostatin inhibitory effect on fat intake may reside in the cyclo-diketopiperazine molecule, cyclo-Asp-Pro. PMID- 7984505 TI - Determinants of potency and temperature-dependent function in the Aplysia bag cell peptides. AB - Structure-activity relationships were determined for the natural bag cell peptides (BCPs) and for a series of synthetic analogues in terms of their ability to stimulate (at 30 degrees C) and to inhibit (at 15 degrees C) bag cell adenyl cyclase. We found that the core RLRF motif shared by all these peptides is active in this assay, and is stimulatory. The histidine residue C-terminal to this motif in beta-BCP is superfluous in this respect. An electronegative residue C-terminal to RLRF is sufficient to induce temperature-dependent function. The Ala-Pro pair that is N-terminal to this motif in alpha-BCP increases potency, but does not alter function. PMID- 7984506 TI - Molecular forms of circulating atrial natriuretic peptides in human plasma and their metabolites. AB - High performance gel permeation chromatography (HP-GPC) followed by four radioimmunoassays (RIAs) devised to amino acids (a.a.) 1-30, 31-67, 79-98, and 99 126 of the 126 a.a. atrial natriuretic factor (ANF) prohormone revealed that the proANF(1-30) assay immunoreactivity in plasma is 50% proANF(1-30) and 50% proANF(1-98). The HP-GPC evaluation of plasma followed by proANF(31-67) and ANF [i.e., proANF(99-126)] assays revealed that proANF(31-67) and ANF circulate as distinct peptides. the HP-GPC plasma examination followed by proANF(79-98) assay immunologically recognized three peaks in plasma consistent with proANF(1-98), (68-98), and -(79-98). Similar HP-GPC evaluation of urine followed by these RIAs indicated that the proANF(1-30), -(79-98), and ANF assays only recognize 500 mol.wt. or less peptides, and the proANF(31-67) RIA recognizes a nearly intact proANF(31-67) with only two to three amino acids removed during processing of this peptide. PMID- 7984507 TI - Chromogranin A(210-301) is the major form of pancreastatin-like material in human gut extracts and endocrine tumors. AB - A radioimmunoassay of human pancreastatin was developed using a rabbit antiserum that selectively recognized the C-terminal amidated end of the peptide, and it was used for the identification of the molecular forms of pancreastatin in human gut (stomach, duodenum, small intestine, colon) and endocrine tumor extracts (liver metastasis of a gastrinoma and a medullary carcinoma of thyroid, one nonsecreting pancreatic tumor, one recurrence of a gut carcinoid, one vipoma and one insulinoma). In all gut extracts, a gel filtration chromatography revealed the presence of three peaks of pancreastatin-like immunoreactivity. The predominant form eluted with an apparent molecular weight higher than that of pancreastatin. This form was also predominant in the endocrine tumors analyzed, except in the insulinoma, where a lower molecular weight form predominated. The high molecular form was further purified from a liver metastasis of a gastrinoma. The pancreastatin-like immunoreactivity eluted in all the chromatographical systems (reverse-phase, ion exchange) as a single peak that was finally purified to homogeneity and sequenced. The sequence of the first 29 N-terminal amino acids was obtained unambiguously and corresponded to the sequence 210-238 of chromogranin A. Considering the selectivity of the assay used for peptide identification, this major form was identified as the fragment 210-301 of chromogranin A. It is likely that the predominant form of pancreastatin in human gut extracts and noninsular tumors is a 92 amino acid peptide. PMID- 7984508 TI - Identification and characterization of two receptors for SchistoFLRFamide on locust oviduct. AB - An in vitro binding assay, using [125I][Y1]SchistoFLRFamide (YDVDHVFLRFamide), an iodinated analogue of SchistoFLRFamide, was developed to demonstrate and characterize putative receptors for SchistoFLRFamide associated with the locust oviduct. Two receptors were revealed by the binding assay. The high-affinity receptor had a Kd of 9.52 +/- 1.15 x 10(-10) M and a Bmax of 14.5 +/- 1.2 fmol/mg membrane protein; the low-affinity receptor had a Kd of 1.86 +/- 0.16 x 10(-7) M and a Bmax of 540 +/- 43 fmol/mg membrane protein. Binding to both receptors was saturable, specific, and reversible, and competitively inhibited by [Y1]SchistoFLRFamide, SchistoFLRFamide, and ADVGHVFLRFamide. Binding was Ca2+ or Mg2+ dependent and was completely inhibited by 2 mM EDTA. The receptors showed a regional distribution, with the majority of the high-affinity receptors associated with the upper lateral oviducts, which receive little or no innervation, and most of the low-affinity receptors associated with the lower lateral and common oviducts, which receive extensive innervation. PMID- 7984509 TI - Ultrastructural evidence for synaptic inputs of enkephalinergic nerve terminals to target neurons in the rat arcuate nucleus. AB - The morphological support of interactions between enkephalins and three systems- beta-endorphin (beta-END), tyrosine hydroxylase (TH), or neuropeptide Y (NPY)- well represented in the arcuate nucleus, was examined by using an electron microscopic double immunostaining combining two sensitive chromogens, diaminobenzidine (DAB) and tetramethylbenzidine (TMB). The first step consisted of visualizing Metenkephalinergic terminals with DAB reaction product, and the second one involved detecting the antigens TH, beta-END, and NPY in their respective neurons with TMB reaction product. Ultrastructural analysis revealed enkephalinergic terminals presynaptic to TH-immunopositive cells and dendrites, principally in the dorsal portion of the arcuate nucleus. Enkephalinergic nerve terminals also contacted synaptically ventrolaterally located beta-END immunoreactive cells. In the ventromedial arcuate nucleus, few synaptic contacts were observed between enkephalinergic boutons and NPY neurons, which were principally in close apposition with glial processes. Enkephalin-immunoreactive synapses were more frequently seen on TH-immunopositive neurons. This TH neuronal group is known to correspond to the dopaminergic tuberoinfundibular neurons implicated in the control of reproductive functions. The pattern of distribution of the different synapses within the arcuate nucleus (TH dorsal, beta-END ventrolaterally; NPY ventromedially) suggests that enkephalins may play a role in the neuroendocrine regulation of gonadotropin and prolactin secretion. The results provide evidence that enkephalins, in the arcuate nucleus, exert a postsynaptic action on the beta-END cells in addition to the presynaptic regulation previously demonstrated in the mediobasal hypothalamus, related to beta-END release. Moreover, the arcuate nucleus is a site of intercellular relationships between enkephalins and dopamine and between enkephalins and other peptides such as NPY. PMID- 7984510 TI - Modulation of active avoidance behavior of rats by ICV administration of CGRP antiserum. AB - The effects of ICV administration of CGRP antiserum on active avoidance behavior were studied in rats. CGRP antiserum dilutions of 1:5, 1:10, 1:20, and 1:40 facilitated the extinction of active avoidance responses in a platform-jumping situation in the 3- and 6-h tests. In the 24-h test, only the CGRP antiserum dilution of 1:5 was effective. The present findings suggest that the endogenous CGRP of the brain may be a physiological modulator in extinction processes of active avoidance behavior. PMID- 7984511 TI - Calcitonin gene-related peptide in medullary thyroid carcinomas: characterization of molecular forms including the amidated C-terminus. AB - CGRP was extracted from three familial and four sporadic medullary thyroid carcinomas (MTC) and was measured by an assay specific for the amidated C terminus. The antibody showed equal affinity for alpha- and beta-CGRP. All tumors contained high concentrations of CGRP (range: 63-7889 pmol/g) compared to spinal cord (86 pmol/g), thyroid gland (4 pmol/g), and two small-cell lung carcinomas (4 and 1 pmol/g, respectively). The concentration of calcitonin (CT) was determined with an assay specific for an epitope involving the midportion and C-terminal end of the molecule. In six of the seven tumors investigated, concentrations of CT were found to be higher than for CGRP. Gel chromatography showed heterogeneity with respect to CGRP immunoreactivity. Thus, in all seven extracts, three peaks were seen with Kd values 0.37, 0.63, and 0.80, respectively. This profile of immunoreactive CGRP was similar to that obtained from human medulla spinalis, thereby indicating normal posttranslational processing of pro-CGRP in MTC tumors. Further characterization of the three main peaks identified by gel chromatography was performed on pooled fractions from one of the tumors using HPLC, sequencing, and mass spectrometry. The immunoreactive peak with Kd 0.37 was identified as human beta-CGRP, the peak with Kd 0.63 as 19-37 beta-CGRP, and the peak with Kd 0.80 as 25-37 beta-CGRP. No alpha-CGRP was identified in this tumor. This indicates selective expression of beta-CGRP, at least in the tumor investigated. PMID- 7984512 TI - Oxytocin augments baroreflex bradycardia in conscious rats. AB - Previous studies have demonstrated augmentation of baroreflex-mediated bradycardia by arginine vasopressin (AVP). However, the specific receptor subtype responsible for mediating this augmentation has not been determined. In the present study, experiments were performed in conscious rats to determine the possible involvement of oxytocin receptors in this response. Infusion of oxytocin at a dose that had no effect on baseline hemodynamic values significantly augmented the bradycardic response to IV bolus doses of methoxamine. Prior treatment with selective antagonists to either oxytocin, V1 vasopressinergic or V2 vasopressinergic receptors reversed this enhancement. In a separate set of experiments, baroreflex-mediated bradycardic responses to IV bolus doses of AVP were assessed. Pretreatment with the selective oxytocin receptor antagonist reversed vasopressinergic augmentation of baroreflex sensitivity. Finally, combined vasopressinergic and oxytocinergic stimulation of the baroreflex was assessed. Treatment with both AVP and oxytocin did not augment baroreflex mediated bradycardia greater than AVP alone. We conclude from these experiments that AVP and oxytocin both augment baroreflex sensitivity, although the receptor type(s) responsible are not clear. PMID- 7984513 TI - Cholecystokinin and estradiol synergistically potentiate satiety in rats. AB - The ability of octapeptide cholecystokinin (CCK), in interaction with ovarian steroid conditions, to decrease 1-h feeding was studied in 5-h food-deprived Sprague-Dawley rats. In Experiment 1, intact, unilaterally ovariectomized, and bilaterally ovariectomized females and intact males were given IP injections of 0, 0.25, 0.50, and 1.0 microgram/kg b.wt. CCK and were assessed for food ingestion at 1, 3, and 19 h. Food intake at 1 h was suppressed in animals receiving CCK compared to saline (0 dose); the threshold dosage was 1 microgram/kg b.wt. (p < 0.01) in this paradigm. No significant sex difference was observed between the four groups; however, animals with decreased ovarian steroids (intact males and bilaterally ovariectomized females) suppressed ingestion less than animals with greater ovarian steroid levels (intact and unilaterally ovariectomized females) at both the 0.25 and 1.0 microgram/kg b.wt. dosages (p < 0.01). Therefore, in a second experiment, sensitivity to CCK was compared in females in early metestrus, when estrogen levels are decreased, and during late diestrus, when estrogen levels are high, using dosages of 0, 0.25, 1, and 2.5 micrograms/kg b.wt. A statistically significant difference was found between sensitivity at early metestrus and late diestrus at the 2.5 micrograms/kg b.wt. dose only, with food ingestion more reliably depressed during periods of increased estrogen (p < 0.05). These results suggest that estradiol and CCK can have a synergistic effect on satiety. PMID- 7984514 TI - Increased expression of angiotensin peptides in the brain of transgenic hypertensive rats. AB - We determined the levels of angiotensin I (ANG I), angiotensin II (ANG II), and the heptapeptide angiotensin(1-7) [ANG(1-7)] in the blood and brain of female Hannover Sprague-Dawley (SD) and transgenic hypertensive rats [mRen-2]27 by radioimmunoassay and high performance liquid chromatography. Hypertension was accompanied by higher plasma concentrations of ANG II, no statistical changes in ANG(1-7), and no differences in plasma ANG I levels. In the hypothalamus of transgenic rats, concentrations of ANG II and ANG(1-7) averaged 827% and 168% above values in SD rats (p < 0.005) whereas both ANG I and ANG II increased in the medulla oblongata. The data showed that the established phase of hypertension in rats harboring the mouse Ren-2 gene is associated with overexpression of the renin-angiotensin system in brain regions participating in the endocrine regulation of blood pressure. PMID- 7984515 TI - Ovarian melanotropic peptides and adaptation in two teleostean species: Sparus aurata L. and Dicentrarchus labrax L. AB - The ovarian tissue of Dicentrarchus labrax and Sparus aurata displays two immunoreactive peaks that correspond to the elution time of human des-acetyl alpha-MSH [ACTH(1-13)-amide] and human alpha-MSH. In view of the close identity between the primary structure of fish and human alpha-MSH, these data demonstrate that two MSH-related peptides are present both in sea bream and sea bass ovary. alpha-MSH-like immunoreactivity was found within both granulosa and thecal layers of mature follicles, as well as in the cytoplasm of oogonia of sea bream and sea bass ovary. Gonadal content of ACTH(1-13)-amide and alpha-MSH display differences with regard to season, showing the highest peptide levels in reproductive animals. Moreover, the alpha-MSH content is significantly higher in the ovary of fish farm animals, whereas that of ACTH(1-13)-amide prevails in wild fish ovary. PMID- 7984516 TI - Hepatic neoformations. AB - The aim of the paper is an accurate histologic description and illustration of those liver lesions that are usually summarized under the heading of "hepatic tumors and related subjects". For in some cases it may be unclear or at least controversial, whether the individual lesion is indeed an autonomous neoplasia or a malformation, regeneration or hyperplasia, the indifferent master term of neoformation is introduced, based on the fact that all of them are characterized by a cellular multiplication. According to common definitory practice the survey distinguishes between mesenchymal (angiomatous and non angiomatous) and epithelial neoformations. Among the latter hepatocellular and cholangiocellular types are distinguished, the criterium for differentiation being a phenomenological one, which is by no means identical with a histogenetical statement. The definition of subgroups mostly adheres to current nomenclatory usage; only occasionally--in the group of endothelial tumors--a novel term is employed, in view of brevity and coordination with the overall system of neoformations. PMID- 7984517 TI - DNA ploidy in carcinoma of the gallbladder. Prognostic significance and comparison of flow and image cytometry on archival tumor material. AB - The aim of this investigation was to determine whether the cytometrically assessed DNA ploidy is a parameter of prognostic significance in gallbladder carcinomas. For this purpose the DNA content of tumor cells from archival tumor material from 80 patients with cholecystic cancer was analysed retrospectively by using comparatively different cytometrical methods, namely flow cytometry (FCM) and image cytometry, using tissue sections (ICM-S) and nuclear suspensions (ICM N). Conventional tumor classifications (according to pTNM and Nevin) were able to predict the further clinical course. DNA ploidy showed a statistically significant correlation only to histological grade (P < 0.001), but not to tumor stage and survival. Only a trend towards a poorer outcome for patients harboring non-diploid tumors became evident especially when no residual tumor was present postoperatively (R 0-stage; P = 0.08). The different cytometrical methods discussed in detail, showed a highly significant concordance in the determination of DNA index values (DI) and in the classification of the tumors as either diploid or non-diploid. In conclusion, our results indicate that cytometrical determination of DNA ploidy provides no further prognostic informations in gallbladder carcinomas as compared to conventional tumor staging. PMID- 7984518 TI - Use of the mitotic counts for the prognosis and grading of breast cancer. Method evaluation study. AB - Reproducibility of the volume fraction-corrected mitotic index (M/VV index) was studied in 144 unselected breast cancer specimens. The influence on decision making of variation in determining the index was also analysed. In the complete series of specimens the correlation between two observers, one subjectively estimating the epithelial fraction of tumor epithelium and the other using point counting (10 x 10 ocular grid), was good (Pearson's r = 0.82, p < 0.001, 95% CI 0.70-0.92). A subset of 30 specimens was used to evaluate the grading efficiency (GE) of the M/VV index method. The mean grading efficiency as estimated from this subset varied between 90% and 93%. The average minimum GE value was 82.8% (SD = 3.4%). The findings suggest that when the M/VV index method is used, the grading is correct on average in 90% or more of the cases, but dependent on the cutoff point. The over-all grading efficiency of the M/VV index method was comparable to that obtained from published S-phase fraction data on breast cancer specimens from three independed laboratories. We conclude that the M/VV index in breast cancer analysis is a sufficiently reproducible method in mitosis counting, and that it can be used with subjective or point count estimation of the area fraction of neoplastic epithelium. PMID- 7984519 TI - Distribution of the VLA family of integrins in normal salivary gland and in pleomorphic adenoma. AB - The extracellular matrix (ECM) and the alterations in tumour stroma affect the biologic behaviour of tumours. These interactions are, at least in part, mediated by the integrin superfamily. In this study we examined the immunohistochemical expression of the "very late activation" (VLA)-integrins in pleomorphic adenomas and in the corresponding normal tissues. Normal salivary gland expresses integrins in the myoepithelial cells (MEC) and in the basal and dark cells of ducts. This pattern is retained in pleomorphic adenoma. Regardless of the straining intensity, these tumour cells have a VLA expression similar to normal basal and dark cells, with only a few cells bearing MEC characteristics. We suggest that the tumour cells of pleomorphic adenoma have a common origin but show different stages of differentiation. Only cells bearing basement membrane (BM)-associated material form typical tubulo-ductal structures. PMID- 7984520 TI - The histological spectrum of acquired nevi. An analysis of the intraepidermal melanocytic proliferation in common and dysplastic nevi. AB - The histological intraepidermal characteristics considered to be specific to dysplastic nevi (radial extension, lentiginous and disordered nest proliferations, cytological atypia or dyskaryosis) were investigated in a series of 114 acquired nevi showing various clinical appearances in an attempt to establish whether dysplastic nevi can be considered a homogeneous class of lesions, clearly distinct from common nevi. On the basis of the distribution of investigated architectural features, found singly or variously associated, the examined lesions were divided into 5 groups, showing an increasing incidence of dyskaryosis. Results suggest that acquired nevi, rather than two distinct classes (common and dysplastic nevi), form a histological spectrum of lesions, within which the border between lesions implying and not implying an increased melanoma risk cannot be objectively fixed. PMID- 7984521 TI - Malignant peritoneal mesothelioma mimicking mesenteric inflammatory disease. AB - A case of malignant peritoneal mesothelioma mimicking mesenteric inflammatory disease (MID) is presented. The patient had mesenteric and omental lesions characterized at biopsy by extensive fibrosis of fat tissue with mild to moderate inflammation. One year later, post-mortem examination revealed a well differentiated epithelial mesothelioma. Immunohistochemical stains for keratin and vimentin were diffusely positive, whereas EMA showed a membranous staining of scattered cells. CEA, Ber-EP4, B72.3 and Leu-M1 were negative. In addition, actin monoclonals decorated groups of cells pertaining to the tumoural component. Immunostains of sections from retrieved paraffin blocks of the previous biopsy showed that the bulk of the spindle-shaped and histiocytic-like cells present in the fibrous streams was strongly labeled by low-molecular-weight keratin, and coexpressed vimentin and actin. EMA showed a membranous staining of sporadic spindle and round cells. The other immunostains were invariably negative. This immunohistochemical pattern closely corresponded to the immunophenotype of the mesothelial tumour detected at autopsy and was very suggestive of myofibroblastic/submesothelial cell origin. The quantitative evaluation of silver nucleolar organizer regions (Ag-NORs) demonstrated high levels of cell proliferation in both surgical and autopsy tissue samples. PMID- 7984522 TI - Blue nevus: classical types and new related entities. A differential diagnostic review. AB - Blue nevus is an uncommon pigmented lesion of dermal melanocytes. By convention, two well defined histologic variants, designated as "common" and "cellular", have been recognised. In the last few years, these lesions have attracted much attention due to the recognition of news entities and to its confusion with malignant melanoma. In the present review, we point out the more striking features of new related entities (combined nevus, deep penetrating nevus, compound blue nevus) and establish the differential diagnosis with conflictive lesions such as atypical blue nevus, locally aggressive blue nevus, congenital giant melanocytic nevus with nodular growth and melanocytic dermal tumor of unpredictable outcome. We also review the concept of malignant blue nevus and the significance of lymph node metastases. The blue nevus is an uncommon pigmented lesion consisting of dermal melanocytes that can appear in diverse forms: dendritic, spindle-shaped, oval-shaped, or polyhedral. Although it usually occurs in skin, it has been reported in other locations, such as oral mucosa, sclera, uterine cervix, vagina, prostate, spermatic cord, pulmonary hilus, orbit, conjunctiva, maxillary sinus, breast, and lymph nodes 3,8,42,49. Generally, it occurs in adults as a single, acquired, intensely pigmented lesion, although familial and multiple nevi have been reported 7,39. By convention, there are two well-defined histologic variants, designated as "common" and "cellular", but lesions often manifest intermediate features. In the last few years, blue nevus has attracted much attention due to the recognition of new (clinical and histologic) entities and to its confusion with malignant melanoma.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7984523 TI - The teaching of organ pathology in European undergraduate programs in medicine, II. PMID- 7984524 TI - [A new cause of familial thrombophilia: resistance to the effect of activated protein C]. AB - An examination of the cascade of events leading to coagulation emphasizes the importance of protein inhibitors. Deficiencies in these proteins have been implicated as playing a possible causal role in familial thrombo-embolic diseases. Recently the discovery of a probable deficiency in protein C cofactor, different from protein S, stimulated much research in this area. Protein C is a 461 amino acid vitamin K-dependent protein with a molar mass of 62,000 Daltons. After transduction the precursor protein is modified into an active form. Circulating protein C is then activated by proteolysis on the endothelial surface under the control of thrombomodulin-bound thrombin. Thus thrombin affects both procoagulation by activating factors V and VIII (and XI) and anticoagulation after being bound to thrombomodulin. Inactivation of factors V and VIII requires calcium, phospholipids and a C-protein cofactor, protein S. On the basis of clinical observations, it was hypothesized then confirmed that deficiency in a non-identified cofactor of protein C could explain resistance to the anticoagulating action of activated protein C. Purification of the plasma fraction carrying the cofactor activity led to the isolation of a protein which has all the biochemical properties of factor V. In addition, adding factor V to affected plasma has been shown to correct for resistance to activated protein C. But paradoxically, patients with resistance to the action of activated protein C have a normal level of factor V. The mutation responsible for activated protein C resistance was found to be a Gln for Arg mutation at position 506 of factor V. The implication of this mutation has been very recently confirmed and led rapidly to the development of molecular biology methods allowing its identification. At present, this new cause of familial hypercoagulable states can thus be identified with polymerase chain reaction and denaturing gradient gel electrophoresis. These advances have increased the number of identifiable hypercoagulable states, yet further work is needed since currently less than 10% of these diseases can be explained by deficiencies in one of the inhibitor proteins, antithrombin III, protein C or protein S. PMID- 7984525 TI - [Measurement of quality of life in intermittent claudication. Clinical validation of a questionnaire]. AB - OBJECTIVES: Functional limitation in patients with intermittent claudication impairs their quality of life. In order to measure this new evaluation parameter, we developed a self-administered questionnaire: Artemis. METHODS: The questionnaire was composed of a general instrument (SF-36) and a specific one. A cross sectional study was performed in 177 patients with intermittent claudication (mean age 68 +/- 10 years, 77% males) who stated their walking distance was limited within 50 to + 2000 meters. The acceptability, reliability and sensitivity of the questionnaire were tested. RESULTS: In patients who had a walking distance greater than 500 m (n = 96), the scores obtained were significantly higher (better quality of life) than in patients whose walking distance was limited to less than 500 m (n = 81) (p < 0.05). Intermittent claudication had a global effect on the different parameters of the quality of life evaluated by the questionnaire including physical performance and psychological and social aspects. CONCLUSION: The Artemis questionnaire as shown its ability to describe patients with intermittent claudication. It can be used in clinical trials as a tool for measuring quality of life. PMID- 7984526 TI - [Acute lymphoblastic leukemia in children. Results of treatment in Sicily 1987 1992]. AB - OBJECTIVES: For several years, children in Sicily with acute lymphoblastic leukaemia have been treated locally at the University of Catania. We compared the results of locally treated children with the results obtained at other centres. METHODS: The diagnosis of acute lymphoblastic leukaemia (ALL) was made in 78 children in the haematology and oncology division of the University of Catania, Sicily, From January 1987 to December 1992. Patients diagnosed before December 1990 were treated with the protocol ALL 87 including prednisone, vincristine, daunorubicine, L-asparaginase and intrathecal methotrexate. Total duration of treatment was 25-26 months. For patients diagnosed after December 1990, the protocol 90-91 used the same drugs for induction and three intrathecal drugs (methotrexate, cytarabine and prednisone) as well as cyclophosphamide to prolong induction in intermediary risk patients. Only high risk patients received cerebral irradiation. Total duration of treatment was 2 years. Full follow-up data were available for 76 patients. RESULTS: Survival rate without relapse was 66% and the 5-year survival rate was 82.7%. These results were comparable with those published by other international groups. In addition, particular attention was given to psychological support to decrease the deleterious effects of both the disease and the treatment protocols. CONCLUSION: These results demonstrate that ALL children can be cared for locally in Sicily without risking poorer outcome. It would be preferable to treat these children as near as possible to their area of residence in order to diminish the psychological trauma resulting from long-term hospitalization far from their family. PMID- 7984527 TI - [Progressive supranuclear paralysis. Quantification of dopamine D2 receptors using radionuclide tomography]. AB - Progressive supranuclear palsy (PSP) may sometimes be misdiagnosed as Parkinson's disease in its early stages, hence an early positive diagnosis of PSP based on dopamine D2 receptor density could be extremely valuable. In the present case report, the absence of dopamine D2 receptors was clearly demonstrated in the striatum using 123I-iodobenzamide (IBZM) tomoscintigraphy. This illustrates the potential use of IBZM tomoscintigraphy to identify Parkinson-like's disease presenting with decreased dopamine D2 receptor density; and hence to predict L Dopa effectiveness. Further studies are needed to evaluate the vaue of IBZM tomoscintigraphy in the different Parkinson's like diseases. PMID- 7984528 TI - [Laparoscopic colpo-suspension by the Burch technique]. AB - The Burch technique is the reference method for the treatment of exertion incontinence related to cervicocystoptosis. We present an original laparoscopic technique equivalent to the classical open approach. This technique is particularly interesting because a wide pneumoretzius allows adequate access for instruments without being hindered by intestinal loops and the free border of the bladder. Suspension is achieved with non-absorbable mesh bands which are attached to the vagina and Cooper ligaments with staples. The anchoring point is thus larger and the space remains blood free. Fifty nine operations were performed with this technique at the Department of Gynaecology of the University Hospital at Caen, France. No failures have been observed. PMID- 7984529 TI - [Hypocholesterolemic statins. Evaluation and prospects]. AB - Statins are a family of compounds which act on cells by inhibiting hydroxymethylglutaryl (HMG) CoA reductase, an enzyme that blocks the intracellular cholesterol synthesis and stimulates the formation and action of LDL receptors. Experience of 3 years after they were introduced in France and 10 years for studies of the first compound (lovastatin) has demonstrated that these drugs are potent hypercholesterolaemia-lowering agents, fairly well tolerated but possibly with some toxicity to muscles. In severe forms of pure hypercholesterolaemia they may be prescribed either alone or combined with biliary acid chelating resins. Their use in mild forms of hypercholesterolaemia will be justified when low-dose preparations are reimbursed by the French Social Security. In mixed hyperlipidaemia, statins are more effective than fibric acid derivatives on cholesterol but weaker on triglycerides. They provide an alternative to fibric acid derivatives when these fail, but they are not indicated in hypertriglyceridaemia. Studies are being carried out to demonstrate that statins have a preventive effect on cardiovascular diseases, in either clinical regression trials or atheromatous plaque regression studies. PMID- 7984530 TI - [Hemorrhagic adrenal gland infarction in thrombopenia caused by heparin]. PMID- 7984531 TI - [Cyclospora, a new coccidium agent of travelers' diarrhea. 11 cases]. PMID- 7984532 TI - [Toxoplasma gondii in the amniotic fluid. Comparison between 2 cell lines for culture isolation]. PMID- 7984533 TI - [Complete arrhythmia caused by auricular fibrillation following epilepsy crisis]. PMID- 7984534 TI - [Neoplastic colonization of trocart paths. Should laparoscopic surgery be stopped for digestive cancers?]. PMID- 7984535 TI - [Recurrent thyrotoxicosis and chronic lymphocytic Hashimoto's thyroiditis]. PMID- 7984536 TI - [Meningoencephalitis, expression of Epstein-Barr virus primary infection in a patient with renal transplantation. Value of the search of the viral genome by PCR]. PMID- 7984537 TI - [Acute necrotizing pancreatitis. When to operate?]. PMID- 7984538 TI - [Measurement of quality of life in rheumatic practice]. AB - Hard, objective data to evaluate outcome in patients with rheumatology diseases is not only difficult to obtain, but often poorly correlated with the degree of the functional incapacity caused by these non-fatal but disabilitating diseases. Soft, subjective data does not meet the traditional criteria for scientific research. However, due to important advances in the field of psychometry and its medical applications, we now have adequate instruments to evaluate quality of life, the major outcome parameter in patients with chronic rheumatic diseases. The Arthritis Impact Measurement Scales is the most widely used and is particularly adapted to patients with rheumatoid arthritis. Other scales include the Health Assessment Questionnaire, the Nottingham Health Profile, and the Sickness Impact Profile. Most of the studies conducted in the field of rheumatology concern patients with rheumatoid arthritis or osteoarthritis of the lower limbs. Quality of life measures can however be applied to most all the different clinical situations including low back pain, ankylosing spondylitis and systemic diseases. Quality of life measures will play an important role in treatment evaluation procedures. They correspond to real progress in responding to the legitimate demand of patient with chronic diseases for effective validated health care. PMID- 7984539 TI - [Cervical plexus block for carotid surgery. 313 consecutive operations]. AB - OBJECTIVES: The optimal method for protecting the brain from ischaemia during carotid surgery is still a matter of debate. The aim of this study was to report our early results after carotid surgery performed with cervical plexus blockade in vigilant patients. METHODS: From 1987 to 1992, 313 consecutive operations were performed on the carotid bifurcation (217 males, 96 females; mean age 67 years; age range 41-87 years). Thirteen underwent bilateral operations at a 1 month interval. There were 118 (38%) asymptomatic patients with carotid narrowing greater than 80% and 195 (62%) symptomatic patients including 96 with temporary cerebral ischaemia, 12 with regressive ischaemic events, 37 with cerebral vascular events and 50 with non-hemispheric events. The contralateral carotid artery was occluded in 30 patients (9.5%). Deep cervical blockade of the C2-C3-C4 roots then superficial blockade was obtained with 0.5% bupivacaine. Operations were endartectomy (n = 301; 96%) including 59 (18.5%) with a prosthetic patch, venous grafts (n = 8; 2.5%) and direct reimplantations (n = 3; 0.9%). All neurological complications observed during the 30 days following operation were recorded. RESULTS: At occlusion, neurological events occurred in 40 patients (12.8%) and required the use of a temporary shunt. In patients with a contralateral occlusion such events occurred in 35.5% of the patients. No cases of myocardial infarction were observed and 1 patient died due to a neurological cause, giving a morbidity of 1.6% and a mortality of 0.3%. CONCLUSION: Cervical plexus blockade was shown to be a simple and effective method for carotid surgery allowing good myocardial haemodynamics and a reliable evaluation of tolerance to occlusion. PMID- 7984541 TI - [Late onset hyperandrogenism caused by 3-beta-hydroxysteroid dehydrogenase deficiency]. AB - OBJECTIVES: Clinical manifestations of hyperandrogenism, including hirsutism and acne with or without dysmenorrhoea are well recognized in late onset hyperandrogenism due to deficiency in 3 beta-hydroxysteroid dehydrogenase (3 beta HSD), yet the frequency of this deficiency in patients with post-puberty hirsutism is not well established. We therefore evaluated retrospectively this deficiency state in women who consulted our unit for manifestations suggestive of hyperandrogenism from 1990 to 1992. METHODS: We included 32 women with clinical manifestations of hyperandrogenism for whom a partial deficit in 3 beta-HSD could be searched for on the basis of hormone assays. Their mean age was 27.5 years (range 14 to 46) and the clinical manifestation was hirsutism in 21 cases, acne in 13, alopecia in 5 and dysmenorrhoea in 11. Diagnostic tests included adrenal stimulation with 0.25 mg beta 1-24 corticotrophin and immunoradioassay of plasma levels of 17-hydroxypregnenolone (17-OHPreg), 17-hydroxyprogesterone (17-OHP), dehydroepiandrosterone (DHA) and cortisol (F). Pang's criteria for the diagnosis of partial deficiency in 3 beta-HSD were retained. We defined deficiency in 3 beta-HSD as certain when the 4 following criteria were present 60 minutes after stimulation: 17-OHPreg > 17.5 ng/ml; DHA > 20 mg/ml; 17-OHPreg/17-OHP > 9; 17 OHPreg/F.10(-3) > 53. Diagnosis was considered probable when only 3 criteria were met and was excluded in all other cases. RESULTS: Positive diagnosis of deficiency in 3 beta-hydroxysteroid dehydrogenase was made in 4 of the 32 patients and probable in 4 others. CONCLUSION: Based on our series of patients, late onset hyperandrogenism due to 3 beta-hydroxysteroid dehydrogenase deficiency would thus appear to be a relative frequent deficiency state. Since therapeutic measures can be taken, this deficiency should be carefully searched for in all young patients presenting with manifestations suggesting hyperandrogenism. PMID- 7984540 TI - [Antihypertensive efficacy and tolerability of diltiazem and enalapril, alone or in combination. DESG. Diltiazem Enalapril Study Group]. AB - OBJECTIVES: Since conversion enzyme inhibitors and calcium inhibitors may have synergic actions, we evaluated the antihypertensive effect and tolerance of prolonged-release diltiazem (300 mg/d) and enalapril (20 mg/d). METHODS: A double blind study included 176 patients with mild to moderate hypertension. Diltiazem was given to 89 (44 males, 45 females, mean age 49.91 +/- 10.50 years, mean resting diastolic arterial pressure 103 +/- 5 mmHg) and 87 (49 males, 38 females, mean age 51.37 +/- 12.13 years, mean resting diastolic arterial pressure 103 +/- 5 mmHg) received enalapril. Single drug therapy was given for 6 weeks and then continued for another 8 weeks in responders. At the end of the first 6-week period non-responders were given a combination regimen (diltiazem 300 mg and enalapril 20 mg). RESULTS: After 6 weeks of single drug therapy, 48 patients in the diltiazem group (61.5%) and 53 in the enalapril group (65.4%) had normal blood pressures which remained normal at the end of the trial 8 weeks later in 36 (76%) and 42 (82%) respectively. After 8 weeks of combined regimen 15 of the 24 non-responders (68%) to single drug diltiazem therapy had normal blood pressures as did 18 of the 23 non-responders (78%) to enalapril alone. Tolerance evaluated clinically, biologically and electrocardiographically was comparable to reports in the literature. CONCLUSION: Delayed prolonged-release diltiazem 300 mg and enalapril 20 mg thus had equivalent antihypertensive effects and were equally well tolerated. Combination therapy increased effectiveness without inducing any additional side effects. PMID- 7984542 TI - [Fluoride therapy. Influence on the microarchitecture and biomechanical properties of bone]. AB - Fluoride, in the form prescribed as sodium or monophosphate fluoride for the treatment of vertebral osteoporosis, modifies the microscopic structure and biomechanical properties of bone tissue. For cancellous bone, the main effect of fluoride is a stimulation of bone formation leading to a hypertrophy of the remaining trabeculae. It may also have a beneficial effect by improving interconnections within the trabecular network. Although the mechanisms have yet to be fully understood, the process is probably dependent on the quality of the remaining network. The biomechanical properties of bone after fluoride therapy also are partly dependent on these modifications in the bone microstructure but also on fluoride's effect on bone minerals. When the concentration of fluoride becomes too high in bone, mineralization defects can occur causing major loss in mechanical resistance despite an increase in bone mass. Thus the beneficial effect of fluoride on wedge fractures of the spine in osteoporosis is probably the result of a balance between the effects of increased trabecular bone mass and modifications in bone mineralization. The respective intensities of these two phenomena also depend on the concentration of fluoride accumulated within the bone. This concentration is a function of the level of fluoride salt intake and its biodisponibility during treatment. PMID- 7984543 TI - [Magnetic resonance imaging in thoracic diseases]. AB - Most all the thoracic structures are visible with magnetic resonance imaging: the mediastin, the myocardium including the endocardium and the pericardium, the pulmonary parenchyma and hile and the pleural walls. In cases of mediastrinal masses, T1 images clearly delimit their relations with neighbouring organs and vessels. The intensity of the signal is compared with that of the muscles on T1 weighted images of the preceding sections and T2 weighted images of fat. Images of aneurysms and chronic dissections can be synchronized with the ECG allowing three-dimensional measurement of the size and thickness of the vessel walls. Thrombi or extension to other vessels can also be recognized. Small hilar tumours can be differentiated from vessels but the scanner is better for analyzing systematization and bronchial lesions. For lung tissue itself, magnetic resonance imaging can detect nodules greater than one centimeter in diameter, but the low proton density and respiratory movements hinder spatial resolution. MRI is indicated for localizing tumours situated anteriorly or posteriorly or at the apex and to identify parietal extension of peripheral cancers. Spinal, vascular, pericardial, diaphragmatic and lymph node metastases can be recognized. MRI is the noninvasive method of choice for evaluating left ventricular masse, intra and paracardiac mass studies and for investigating congenital and acquired cardiomyopathies. Technical advances have made it possible to evaluate myocardial perfusion and heart function. PMID- 7984544 TI - Role of muscle capillarization and morphology in the development of insulin resistance and metabolic syndrome. PMID- 7984545 TI - [Recurrent paralysis disclosing Lyme disease]. PMID- 7984546 TI - [Subhepatic abscess on residual peritoneal biliary calculi after laparoscopic cholecystectomy]. PMID- 7984547 TI - [Early syringomyelia after spinal cord injury]. PMID- 7984548 TI - [Hypercalcemia in an infant caused by exclusive intake of high calcium mineral water]. PMID- 7984549 TI - [Neuromeningeal listeria infection in adults, clinical and therapeutic aspects. Retrospective study of 17 cases]. PMID- 7984550 TI - [Noncovalent immobilization of catalase on antibodies adsorbed on carbon fabric]. AB - Catalase was immobilized on an immunosorbent prepared by anticatalase adsorption on an activated carbon fabric (ACF), and its kinetic parameters were determined. The immobilized catalase activity depended on the binding capacity of anticatalase. Under the optimum conditions (6 micrograms/mg anticatalase, 5.24 nM catalase) the immobilized catalase activity was 1.5-ford higher as compared to soluble catalase. Antibodies stabilized soluble catalase, but decreased its thermostability on immobilization of immunocomplexes on ACF. Noncovalent immobilization of catalase on adsorbed antibodies opens up the way to the use of this approach for immobilization of other oligomeric enzymes. PMID- 7984551 TI - [Isolation of riboflavin-binding apoprotein from chicken egg protein and its use for determining riboflavin in biological samples]. AB - A riboflavine-binding protein has been isolated from egg white and its properties have been characterized. The apoprotein-employing techniques for riboflavine detection in foods, urine, and blood serum are highly competitive with conventional labor-consuming procedures and with the high expensive HPLC method in sensitivity and selectivity, and can be recommended for riboflavine detection in biological objects. PMID- 7984552 TI - [Physiologically active substances from the fungus Coriolus hirsutus (Fr.) Quel]. AB - The fungus Coriolus hirsutus is able to synthesize physiologically active compounds with a high antioxidant activity. The level of the antioxidant activity is mainly determined by phenolic constituents and makes up 90-95% of ionol activity. The experiments carried out in test animals have shown hypolipidemic and hypocholesterolemic effects of the fungus alcohol extract. PMID- 7984553 TI - [The interconnection of the level of unsaturated fatty acids and vitamin E in food product lipids]. AB - The relationship between the contents of unsaturated fatty acids and vitamin E in lipids of cereal and leguminous seeds, vegetable oils, milk and meat has been examined. For all the food products studied the following tendency was observed: the concentration of vitamin E increases in parallel with the concentration of unsaturated fatty acids. PMID- 7984554 TI - [Distribution of nitrate- and nitrite-ions in a two-phase system of water-fat free milk--anionic carboxyl containing polysaccharide]. AB - The distribution of nitrate and nitrite ions between the equilibrium phases in the two-phase water--fat-free milk proteins--polysaccharide system has been studied. The partition coefficient was independent of the structure of the polysaccharide used (pectin, sodium salt of carboxymethylcellulose), its concentration, ionic strength of the solution and temperature, and was equal to 1.20 +/- 0.05. This can be explained by the absence of interactions between nitrate and nitrite ions and bipolymeric components of the system. The deviation of the Kd value from unit may be due to the different proportion of the solvent, water in the phases. The partition coefficient calculated with regard to this proportion was close to unit (1.06 +/- 0.05). PMID- 7984555 TI - [Incidence and duration of recurrence of respiratory tuberculosis in adults]. AB - The relapse-free interval after the primary treatment has been studied in 1165 adults with respiratory tuberculosis (RT) who has developed the recurrent disease. Early recurrences (in follow-up group III) were recorded within 2-3 years since the treatment completion. Late recurrences occurred in group VII-A 9.7 years, in patients crossed off the register 13.1 years after the treatment. New principles of antituberculosis service at specialized dispensaries proposed by the authors promote more efficient regimens of treatment, more rapid cure. It secures a stable rate of recurrences which does not exceed 1.2% from those treated. PMID- 7984556 TI - [Effectiveness of team-expedition examination of adult population epidemiologically at risk for tuberculosis in rural districts]. AB - A team of skilled physicians for 4 years went on field expeditions to examine rural population of a territory epidemiologically unsatisfactory by tuberculosis. The activity of the team contributed to improvement of the epidemiological situation in the region and advancement of the local medical staff qualification. PMID- 7984557 TI - [Tuberculosis in cooperative workers]. AB - Out of 67 cooperators with tuberculosis treated at the city antituberculosis dispensary the advanced disease was found in 68.5% of the cases. Of them 67.7% discharged tubercle bacilli, 38.4% had multiple caverns. Among the reasons for a severe specific process in the lungs are intensive labour, late working hours, lack of social and health protection. PMID- 7984558 TI - [Treatment of patients with pulmonary tuberculosis in a day hospital]. PMID- 7984559 TI - [Characteristics of epidemiology and clinical course of pulmonary tuberculosis in inhabitants of Northern Russia]. AB - Pathogenetic and clinical features of the disease were studied in 126 tuberculous patients living in the North of Russia. Tuberculomas in them were found to form primarily from a caseous-pneumonic focus, clinical symptoms were manifest. Anatomically, homogeneous tuberculomas predominated in the immigrants, while a laminar type occurred more frequently in the native population (34.5 +/- 0.14% against 4.5 +/- 0.16%). PMID- 7984560 TI - [Epidemiological risks of tuberculous infection foci in patients discharging L forms of Mycobacterium tuberculosis]. AB - It is shown that patients from dispensary follow-up groups II, III and VII who discharge M. Tuberculosis L-forms demonstrable after repeated (two) examinations are epidemiologically dangerous to surrounding people. Preventive measures in the families should be based on the duration of the contact with the carrier, social and household conditions, stability and frequency of L-forms isolation. Unstable L-forms are found reversible. In new cases of the above infection from the families at risk the disease runs with scarce symptoms, predominance of respiratory infiltration and solitary destructive lesions, slowly regressive inflammation. PMID- 7984561 TI - [Characteristics of thanatogenesis and pathomorphology of tuberculosis in the Gomel region in relation to the Chernobyl AES accident]. AB - On the basis of 750 autopsy records fatal outcomes were studied in Gomel and Gomel region for the period of 5 years after the Chernobyl accident and for the same period in Minsk and Minsk region. A stereomorphometric method was used for studying thymus morphostructure in 20 fatal cases of tuberculosis among the population of Gomel. Certain specific features of tuberculous thanatogenesis and pathomorphology have been revealed which were most pronounced on the monitored territories of the Gomel region and which manifested themselves in the more remote terms (4-5 years) after the Chernobyl accident. Mortality from fibrocavernous pulmonary tuberculosis with massive destructive components and copious bacilli excretion increased to 63.2% and that from disseminated forms of tuberculosis to 22.5%. In regions under the strict control the frequency of tuberculosis progress among the principal causes of death with the development of caseous pneumonia has grown to 55.5% as against 31.8% on the less contaminated territories (to 1 Ci/km2). The thymus underwent deep reorganization which was inadequate to the severity of the principal disease and age. The evidence of this was overstrain of adaptational-compensatory mechanisms of the immune system that finally led to the development of T-immunodeficiency in 55.3% of the patients. PMID- 7984562 TI - [Serological diagnosis of tuberculosis in children by using erythrocyte preparations]. AB - The results of indirect hemagglutination with phosphatide and protein antigens in children with different manifestations of primary Tb infection point to a high diagnostic potential of the serological method. Specially designed and tested diagnostic preparations made of TB and BCG vaccine strain tuberculin can perfect the diagnosis of tuberculosis and determination of its activity. Employment of the erythrocytic diagnosticum with BCG tuberculin extends the potential of detecting postvaccinal complications in children immunized with BCG vaccine. PMID- 7984563 TI - [Possibilities and prospects of intravascular irradiation of blood by helium-neon laser in patients with pulmonary tuberculosis]. AB - The authors report a bacteriostatic effect of He-Ne laser irradiation on Tb growth. Endovascular blood irradiation used in 85 tuberculous patients induced no side effects. Ten-twelve sessions relieved the symptoms of tuberculosis-related intoxication, reduced the infiltration and destruction, promoted abacillosis. Laser irradiation holds promise in management of torpid infection and hepatotoxicity induced by isoniazid and rifampicin. The highest effect occurred in infiltrative tuberculosis. PMID- 7984564 TI - [Clinical and immunologic characteristics of patients with histiocytosis X]. AB - Characteristic features of the clinical course and immune status were studied in 24 histiocytosis X patients. Immunologic studies were carried out in 15 histiocytosis X patients by the methods that characterize the T- and B-lymphocyte systems, their sensitivity to tuberculin, the receptor apparatus of lymphocytes and neutrophilic granulocytes and autoimmune processes. The immune status of these patients is distinguished by disorders caused by secondary cellular deficit combined with the imbalance of the immunoregulatory cell system. Disorders of the B-cell link of the immune system are less pronounced and there is a drop in the production of natural antibodies and IgM. A high degree of sensitization to tuberculin was detected in the in vivo and in vitro tests, which indirectly testifies to the tuberculous origin of histiocytosis X. PMID- 7984565 TI - [Ultrasound stimulation of the urinary tract in patients with nephrotuberculosis as a method of functional restoration of ureteral capacity]. PMID- 7984566 TI - [Concept of accelerated cure of destructive pulmonary tuberculosis]. PMID- 7984567 TI - [Experience in intensive combined treatment of urogenital tuberculosis]. PMID- 7984568 TI - [Pathogenesis, early diagnosis and treatment in tuberculosis of peripheral lymph nodes]. PMID- 7984569 TI - [Results of a combined use of the tuberculin provocation test and immunoenzyme analysis in phthisis]. AB - In patients with early respiratory tuberculosis serum levels of specific antibodies were measured before and after Koch's test using an enzyme immunoassay (EIA). The latter was most informative in evaluating the baseline level of the antibodies to make a differential diagnosis of tuberculosis. When followed by EIA, the tuberculin provocative test enhances EIA sensitivity thus contributing to more effective detection of specific process of minor activity. PMID- 7984570 TI - [Effects of infrared laser irradiation on immunologic reactivity of patients with infiltrative pulmonary tuberculosis]. AB - Influence of chemo- and laser therapy on the state of immunologic reactivity was studied in 38 patients with infiltrative pulmonary tuberculosis. It was found that the arsenide-gallium laser used in combined therapy of infiltrative pulmonary tuberculosis produces an immune-stimulating action and has a favourable effect on the course and outcomes of the disease. Infra-red laser radiation produces most favourable effect when it is used two times. PMID- 7984571 TI - [Characteristics of biological properties of the causative agent in patients with pulmonary tuberculosis exposed to prolonged low-dose radiation]. AB - Strains of M. tuberculosis isolated from tuberculous patients exposed to low-dose radiation after the Chernobyl accident were compared to those obtained from tuberculous non-irradiated controls for L-forms incidence, L-transformation and virulence. A total of 31 cultures were examined in vivo. In response to L transforming preparations the frequency and rate of L-forms induction in the test strains were much higher than those in the controls. The same tendency was registered for virulence. PMID- 7984572 TI - [Effects of pulmonary surfactant on the activity of interleukin-1 secreted by macrophages in normal state and in pulmonary fibrosis]. AB - The article deals with the study of the influence produced by pulmonary surfactant on the activity of interleukin-1 secreted by macrophages which were isolated from the lungs of Wistar male rats 3 weeks after they were given a one time administration of bleomycin or sodium chloride isotonic solution. Under conditions of prostaglandin synthesis stimulated by lipopolysaccharides and simultaneously inhibited by indomethacin macrophages of the lungs with forming fibrosis secrete an increased amount of interleukin-1. Cultivation of macrophages isolated from fibrosis-affected lungs with surfactant was also accompanied by enhanced activity of this monokine. Interleukin-1 secretion by macrophages of animals with fibrosis was drastically increased in the presence of polymyxin B. Under the same conditions pulmonary surfactant significantly stimulated the activity of monokine which was secreted both by cells of the normal animals and by those obtained from the lungs with fibrosis. Consideration is given to the importance of this phenomenon for the pathogenesis of pulmonary fibrosis. PMID- 7984573 TI - [Gene geography of hereditary glucose-6-phosphate dehydrogenase deficiency and pulmonary tuberculosis in Azerbaijan]. AB - A comparative study of the detection rate for glucose-6-phosphate dehydrogenase (G-6-PDH) deficiency was carried out among the indigenous population of different regions of Azerbaijan with epidemiologic tuberculosis situation. A screening comprising the Bernstein test (for revealing enzymopathy in the erythroid series cells) and the NS test (for revealing enzyme deficiency in leukocytes) was conducted to find hereditary G-6-PDH deficiency. A comparison of the epidemiologic parameters of the pertinent regions revealed the correlation between the detection rate for G-6-PDH deficiency in the republican regions and the epidemiologic tuberculosis situation. These studies have led to the conclusion that one of the measures to reduce tuberculosis morbidity in the republic is to enhance antiepidemiologic measures in the regions whose residents show a high incidence fo hereditary G-6-PDH deficiency. PMID- 7984574 TI - [T-lymphocyte subpopulations in tuberculosis in middle aged and aged patients]. AB - The role of T-lymphocyte subpopulations in regulation of immunity was studied using monoclonal antibodies OKT-4 and OKT-8 in tuberculous patients and healthy subjects of different age. Basing on the examination of 174 patients, it was established that in older subjects pulmonary tuberculosis runs in the presence of aged-related changes in the immune system: an increase in the number of T suppressors, a reduction in that of T-helpers, secondary immunodeficiency dependent on the process severity and forms. These shifts are suggested to be responsible for the inadequate immune response to M. tuberculosis in the elderly. PMID- 7984575 TI - [Level and spectrum of tuberculosis antibodies in mice sensitive and resistant to tuberculosis]. AB - The level and spectrum of antituberculous antibodies (AA) were assessed in mice and their hybrids sensitive or resistant to tuberculosis. The AA level in resistant animals (CBA) and hybrids (CBA x C57Bl/6) F1 surpassed that in the sensitive mice (C57Bl/6). The spectrum in resistant and hybrid mice appeared more varied than that in the sensitive animals. Resistant mice had bands in the range 15-20 kD. PMID- 7984576 TI - [Morphology of changes in bronchial vessels in chronic inflammatory diseases of the lungs and their role in the development of pulmonary hypertension]. AB - Histologic and morphometric examination comprised surgical and autopsy material of 20 patients with bronchiectatic disease and 14 patients with chronic bronchitis, respectively. The control group consisted of 14 autopsy follow-ups of the lungs of subjects who had neither pulmonary diseases nor heart defects. Structural reorganization of the lungs in both diseases was characterized by enlargement of the middle and inner coats of arteries, hyperplasia of their inner elastic membrane and hypertrophy of the middle coat of veins. Changes mainly developed on the level of the subsegmental bronchi and bronchiectases. A direct correlation was seen between the degree of hypertrophy of the walls of bronchial vessels and those of the pulmonary artery. Participation of bronchopulmonary shunting in the development of lung hypertension is discussed. PMID- 7984577 TI - [Course of infiltrating pulmonary tuberculosis depending on the patient's genotype]. AB - To compare the disease course with regard to genetic markers carriage, the authors have examined 84 tuberculous patients. It was established that carriers of antigen HLA-DR2 and haptoglobin phenotype 2-2 have large cavities of destruction and more advanced dissemination. This trend is more evident in combination of above markers. These carriers are also noted to exhibit less advantageous run of pulmonary tuberculosis as shown by longer terms of the bacterial isolation and cavern healing. PMID- 7984578 TI - [Medical and economic standards in antituberculosis services]. AB - To meet the requirements of insurance medicine to be introduced in this country, special medical and economical standards as regards tuberculosis have been developed for antituberculosis services. The standards summarize and systematize the minimum preventive and treatment measures to be provided for the population of the districts and regions. Criteria of the treatment quality have been formulated. The patients of the antituberculosis institutions have been grouped by curability, follow-up duration, operability. The standards are to help in granting licences, opening credits for treatment and prophylactic institutions and in controlling their activities under insurance medicine. PMID- 7984579 TI - [Use of a method of standardization of activity indicators in the evaluation of the antituberculosis aid to the population]. AB - To advance medical management at the regional level, it is recommended to introduce a statistical method of standardization for a comprehensive estimation of the efficacy of the antituberculosis measures. The estimation of the fixed rates and integrated values by groups of homogeneous characteristics is detailed. The latter involve epidemiological situation and its sequelae for the population health, preventive measures against tuberculosis, follow-up and treatment efficacy. Criteria of integrated estimates for regional activities are outlined. PMID- 7984580 TI - [Experience in the use of the automated planning system for fluorographic examinations in a rural area]. AB - A. personal computer-based information system meeting the requirements of the RF Ministry of Health on mass fluorographic examinations is proposed for introduction in wide practice. The system provides significant and complete data on the population subject to preventive check-ups, raises the efficacy of the latter, makes automatic planning. PMID- 7984581 TI - [Bacteriological diagnosis of tuberculosis]. PMID- 7984582 TI - [Level of sanitary-hygienic knowledge and habits of tuberculosis patients and ways of raising it]. AB - The anonymous questionnaire method was used for the study of the level of sanitary-hygienic awareness and habits of 236 tuberculosis patients on admission and during their stay in a antituberculosis dispensary. Studies among the newly admitted patients have revealed significant differences in the level of tuberculosis awareness. More than 40% of the patients had no idea of the infectious nature of the disease on the day of admission, two-thirds of them did not know about a source of infection, factors and ways of tuberculosis transmission and nearly 90% could not handle sputum and use spitoons, toilet accessories and disinfectants. The level of patients' awareness and habits related to tuberculosis prophylaxis undergoes basic changes and reaches 98-100% provided all forms and methods of sanitary education and training are fully employed during their stay at antituberculosis hospitals. Interestingly, the more time the patient stays at a hospital, the less he believes in his cure. Questionnaires revealed a high-risk group of patients (29.7%) who present danger for the subjects around in respect to tuberculosis dissemination due to the infringement of the sanitary-hygienic and therapeutic and preventive requirements and recommendations. PMID- 7984583 TI - [Indicators of systemic and local immunity in patients with spinal tuberculosis]. AB - The examination of 33 patients with tuberculous spondylitis and its sequelae revealed inhibition of T-cell immunity in 40% of the examinees, antituberculous antibodies in the blood of 73% of patients. An enzyme immunoassay detected antituberculous antibodies in cerebrospinal fluid of 70% seropositive sufferers with spinal tuberculosis. Positive results of this test serve a direct indication to spinal decompression and intensive pre- and postoperative antituberculosis treatment. PMID- 7984584 TI - [Improvement of differential diagnosis of tuberculosis and cancer of the lungs based on a mathematical method]. AB - A table differential diagnosis algorithm has been developed to improve the diagnosis of tuberculosis and lung cancer in tuberculosis institutions. The algorithm proved effective already at the stage of primary antituberculosis aid, being a reliable tool in the diagnosis of lung cancer and tuberculosis, contributing to shorter examinations of patients, earlier administration of adequate treatment. PMID- 7984585 TI - [Roentgeno-anatomical correlations in infiltrative pulmonary tuberculosis based on resection materials]. AB - The material of 97 pulmonary resections for large caseous focuses of tuberculosis was compared to relevant x-ray and morphological evidence. Roentgenologically, caseous-necrotic foci may be stable for a long time (6-12 months) in spite of the absence of the fibrous capsule. In view of these findings, x-ray potentialities in the diagnosis of the process form and phase are considered. PMID- 7984586 TI - [Use of levamisole electrophoresis in chemical prophylaxis in adolescents with a change in tuberculin reaction]. AB - Immunological reactivity was assessed in 108 adolescents aged 12-17: 25 healthy subjects, 29 and 54 adolescents with a turn in tuberculin tests. The latter received isoniazid alone for 3 months and in combination with levamisole electrophoresis, respectively. Immunological reactivity responded more advantageously in 54 subjects exposed to adjuvant levamisole electrophoresis. They showed inhibition of immunospecific reactions and enhancement of nonspecific ones as well as of skin tuberculin sensitivity. Levamisole electrophoresis raised the efficacy of secondary prophylaxis in adolescents with a turn in tuberculin tests. PMID- 7984587 TI - [Expression of intoxication syndrome in patients with destructive pulmonary tuberculosis discharging Candida fungi]. AB - The severity of intoxication in tuberculous patients with destructive forms was quantified as the number of middle-size molecules. Diagnostic criteria for Candida infection are provided in the range from Candida carriage to invasive candidiasis basing on enzyme immunoassay and bacteriological examinations findings. Candida carriage is shown to be of little relevance to the intoxication progress and severity, whereas mucosal dissemination on the bronchial tree and subsequent development of the mycotic lesion affect intoxication symptoms aggravating tuberculosis course. PMID- 7984588 TI - [Statistical analysis of liver dysfunction in patients with pulmonary tuberculosis using the data base control system]. AB - A program HEPATOX has been devised for the study of the frequency of hepatic dysfunction signs within the system of data base control FoxPro. The analysis of the data available for 377 tuberculous patients showed a more important role of the laboratory diagnosis compared to clinical symptoms, a predisposing role of prior hepatitides and active inflammation in the onset of hepatic dysfunction in conditions of on-going chemotherapy. The authors present the frequency spectrum for clinical and laboratory findings from tuberculous in patients with liver dysfunctions. The efficacy of computers in phthisiopulmonology is demonstrated. PMID- 7984589 TI - [Use of non-medicamentous methods of treatment with the aim to improve the immune status of patients with suppurative diseases and malignant neoformations of the lungs]. AB - A test group of 40 patients and a control group of 20 matched controls with pulmonary cancer and suppuration were exposed to preoperative and postoperative electromyostimulation (EMS) with adjuvant intravascular laser radiation of the blood (ILRB) to prevent thromboembolism versus conventional chemotherapy, respectively. At the preoperative examination all the patients exhibited secondary immunodeficiency. It was found that introduction of EMS and ILRB corrects immunity and activates fibrinolysis. A positive trend in coagulation is also attributed to immunomodulating effects of EMS and ILRB. PMID- 7984590 TI - [Characteristics of examination and treatment of patients with tuberculous chorioretinitis at the specialized sanatorium]. PMID- 7984591 TI - [Significance of lymphocyte blast transformation reaction in the diagnosis of ocular tuberculosis]. PMID- 7984592 TI - [Clinical and laboratory criteria of endogenous intoxication in patients with pulmonary tuberculosis and effectiveness of detoxification therapy]. AB - Endogenic intoxication (EI) tests were conducted in 191 patients with pulmonary tuberculosis. 40 healthy subjects served control. In tuberculosis patients EI depended on the disease clinical form, dissemination, destruction. Administration of detoxication therapy at the start of the combined treatment promoted rapid EI reduction. Due to detoxication, side effects of the drugs occurred 3 times less frequently, the efficacy of the treatment rose. Minor hemosorption resulted in detoxication effects superior to those of transfusions. EI classification is suggested, the prognostic value of EI tests is ascertained. PMID- 7984593 TI - [Correction of antioxidant defense in patients with bronchial asthma by the method of intravascular laser irradiation]. AB - Adjuvant endovascular irradiation of blood with He-Ne laser was used in addition to conventional treatment for bacterial asthma. Out of 48 asthmatics, 16 had a mild disease, 21 moderate, 11 severe forms. The course of treatment included 8-10 daily sessions lasting 30 minutes. A marked clinical response was achieved in 41 patients. The cessation of the asphyxia attacks in them allowed discontinuation or reduction of glucocorticoids administration. The duration of the exacerbations became shorter. The irradiation also stimulated the blood antioxidant system. PMID- 7984594 TI - [Effects of low-energy laser irradiation on blood biochemical parameters in experimental chronic obstructive bronchitis]. AB - The study established that shifts in oxidant-antioxidant system induced by chronic obstructive bronchitis are correctable by He-Ne laser irradiation. This conclusion was based on biochemical indices of the blood measured in experimental animals: lipid peroxidation, general antitryptic activity of the serum, activity of the enzymes superoxide dismutase, gamma-glutamyl transferase, pseudocholine esterase, alpha-oxybutyrate dehydrogenase, glucose 6-phosphate dehydrogenase. PMID- 7984595 TI - [Changes in human pulmonary receptors in tuberculosis, chronic pneumonia and cancer]. AB - The authors studied changes in beta- and alpha 1-adrenoceptors (beta-AC, alpha 1 AC) as well as in m-cholinoceptors in tuberculosis, pneumonia and cancer. Specimens of the lung parenchyma were obtained at thoracic surgery from 43 patients. Relevant ligands binding to the receptors was evaluated by incubation of the membrane proteins with radioligands varying in concentrations. Irrespective of the inflammation variant, beta-AC and alpha 1-AC levels were found decreased this being an correlation with the scope of fibrous and destructive involvement. The degree of the process chronicity and advance was judged from a decline in the binding parameters for beta-AC and alpha 1 AC. A dramatic fall in alpha 1 AC occurred in tuberculosis. This may be related to microcirculatory failure and vascular deformity. The levels of m-cholinoceptors underwent insignificant changes in pulmonary inflammation, whereas lung cancer displayed their sharp rise. PMID- 7984596 TI - [Evaluation of the severity of tuberculous process in mouse lung]. AB - A method for quantitative evaluation of lung affection degree in experimental tuberculosis mice has been elaborated according to the findings of macroscopic study. Consideration is given not only to the productive changes in the lungs, but also to the manifestation degree of exudative reactions. The proposed criteria are presented in a formalized pattern that is suitable for any mathematical treatment. PMID- 7984597 TI - [Circadian rhythm of pituitary-adrenal and pituitary-gonadal systems in patients with pulmonary tuberculosis]. AB - Circadian rhythms were investigated in the levels of ACTH, FSH, LH, hydrocortisone, testosterone, progesterone and estradiol in 12 healthy subjects against 32 patients suffering from infiltrative lung tuberculosis. It was found out that healthy subjects have fluctuations in the above hormones which come to an acrophase in morning hours (at 7-8 a.m.), have high mean values, stable time and amplitude structure. In contrast, tuberculosis patients exhibited impaired circadian cycle of the hormones with acrophase in day and evening hours (16-20 p.m.), reduced mean levels and amplitude in fluctuation, non-coincidence in time. The derangement in the rhythm was more distinct in disseminated tuberculosis with intoxication symptoms. PMID- 7984598 TI - [Associated lesions of peripheral lymph nodes in tuberculosis and malignant tumors]. PMID- 7984599 TI - [Hypothesis of natural foci of tuberculosis]. PMID- 7984600 TI - [Prevalence of radioactive particles in the territory of Byelorussia and their contents in the lungs]. AB - Examination conducted in 1987--1988 included 200 samples of the autopsy material of subjects who died of various causes in different regions of Byelorussia. It revealed the presence of "hot" particles (i.e. particles with high specific radioactivity) in 50% of the samples taken from the northwest and in 70% of those from the southeast regions. A correlation was found to exist between the radioactive particles content in the soil, air and lungs of residents from the contaminated territory. It was shown that in 1990--1991, in contrast to 1987- 1988, the particles content in a single lung sample reduced, which was associated both with mechanical removal of particles and their disintegration and, as a consequence with the accumulation of plutonium in the body. Study of radioactive particles distribution in the whole lung showed that at present they are found primarily in the lower segments. PMID- 7984601 TI - [SociaL aspects of pulmonology]. AB - A group of new-onset pulmonary tuberculosis patients has been studied and its social characterization is provided in the paper. Comparison of the 1991-1992 findings with those obtained in 1970-1980 has indicated that social aspects are topical as before and have some specific features in recent years. The most important issues are now living conditions, financial status of the patients, their social lifestyle, refugees and rational employment of tuberculosis patients and disabled persons. PMID- 7984602 TI - [Characteristics of clinical course of pulmonary tuberculosis in penitentiary population]. AB - The course of consumption was studied in 374 residents of the Sverdlovsk Region who had been in prison for different periods of time. Among them, there were prevalent young males with lower educational and professional levels, who were single or divorced, and had a poor social status. A third of the patients had fallen ill mainly in the first 5 years of imprisonment. The disease was detected in the half of the remaining persons in the first 3 years after imprisonment. Despite frequent cases with severe tuberculosis, long-term multimodality therapy allowed the tuberculosis process to be adequately treated and the disease to be cured in most patients. The main cause that aggravates the course of tuberculosis is the patients' refusal to take a systematic treatment. PMID- 7984603 TI - [Pregnancy and delivery as risk factors for tuberculosis]. AB - A total of 1,474 females who fell ill with tuberculosis in the reproductive age in 1988-1992 (12% of them fell ill during pregnancy and after labour) and 690 pregnants were examined. The tuberculosis detection rates in pregnants and parturients in Moscow were 1.5-2 times higher than the average rates in the above period. The women who fell ill during pregnancy and just after labour frequently developed acute, frequently complicated forms of the process, which were close to the primary forms in their genesis. Contact film thermoindication is an effective method of detecting respiratory diseases in pregnant females (3/4 of clinical and thermoscopic coincidences). A risk group for tuberculosis was identified among the pregnants, which was 6.5% of the examinees: those who had been registered at the tuberculosis dispensary or had contacts with patients; those who suffered from chronic non-specific respiratory diseases or had steady-state thermal asymmetry. PMID- 7984604 TI - [Effect of chemical environmental factors on risk for various forms of pulmonary tuberculosis]. AB - The correlation-regression analysis, including that on an EC-1036 computer, was used to examine the quantitative dependence of tuberculosis morbidity on the man made pollutants of the air. Prognosis of various forms of tuberculosis have been worked out. Out of the atmospheric pollutants, carbon dioxide heads the list, sulfur dioxide ranks next, the less effects are produced by nitrogen dioxide. The highly determined multiple correlation coefficients suggest that there is a combination of chemical pollutants which can have effects on morbidity due to various types of pulmonary tuberculosis. The calculated multiple determination coefficients are 30.1, 80.2, and 66.1% in disseminated, focal, and fibrocavernous tuberculosis, respectively. PMID- 7984605 TI - [Tuberculosis statistics by sectional data]. AB - Analysis of sectional schedules and autopsy protocols for 1,061 persons who died of tuberculosis in Saint Petersburg in 1984-1991 has provided data on the age and sex distribution of the victims, the distribution of various types of tuberculosis as the underlying or concomitant disease, on the incidence and pattern of its complications, concurrent and competitive abnormalities and the causes of death. Comparison of previous results of the previous studies made regularly since 1981 has revealed stable and labile statistical parameters that characterize the evolution of tuberculosis as a disease, its pathomorphism in Saint Petersburg over the past century. PMID- 7984606 TI - [Effectiveness of chemotherapy combined with ultrahigh-frequency electromagnetic radiation for the treatment of patients with pulmonary tuberculosis]. AB - A procedure was developed to determine the optimum wavelength used for each patient individually. Ultrahigh-frequency electromagnetic radiation was studied in 54 patients with various pulmonary tuberculosis forms for its impact on the course of the disease. Treatment was performed by using a YAVOR device at 6.4 and 7.1 mm. Is was found that following 10 sessions of UHF therapy used in combination with specific chemicals, caverns were closed in 50% of patients 2-3 months after therapy and in the controls 5-6 months later. Infiltrates in the lesion areas were resolved 2-3 weeks after UHF exposure, whereas in the controls 1-2 months following drug therapy alone. PMID- 7984607 TI - [Analysis of various risk factors in high risk groups on development of premorbid conditions in chronic non-specific lung diseases]. PMID- 7984608 TI - [Dynamics in bacterial isolation and antigenemia in patients with infiltrative pulmonary tuberculosis]. AB - A hundred patients with infiltrative pulmonary tuberculosis were studied. They were examined for bacterial isolates and mycobacterial antigens in the immune complexes. The isolates were detected in 76%. In most cases, isolation stopped 3 months following chemotherapy and in the absolute majority of cases (except one) 9 months after. Isolation of L-forms remained for a longer period of time, at month 6 of therapy there was an increase in the number of patients who were found to have L-forms of the bacteria. Most (97%) patients with infiltrative tuberculosis displayed mycobacterial antigens circulating in the immune complexes. Antigenemia retained in a considerable (40%) number of patients long (up to 9 months) and in most cases with the unfavourable course of the disease. PMID- 7984609 TI - [Immunologic methods and their use for diagnosis in the treatment of pulmonary tuberculosis]. AB - The immunological survey of 1,688 patients with tuberculosis and 486 with non specific pulmonary diseases was made. Criteria were identified for immunodiagnosis. The use of current mathematical methods of analysis allowed the development of high performance immunodiagnostic systems for pulmonary abnormalities, which included diagnostic tables and discriminant analysis by employing a computer. The major immunological disorders were determined, which in agreement with the definite direction of a tuberculous process with the subsequent use of data for monitoring the patient's status and correcting the treatment. The most potent immunocorrective drugs were studied, indications for their use were specified, proceeding from the immunological characterization of a specific patient. It was shown that the comprehensive assessment of various links of the immune system is of undoubtful value for the diagnosis and prediction of diseases, and prescription of immunocorrective therapy for pulmonary tuberculosis. PMID- 7984610 TI - [Differential-diagnostic value of detecting L-forms of Mycobacterium tuberculosis]. AB - A clinical and bacteriological study was made of 144 patients with new-onset pulmonary tuberculosis who had been treated within the first 3-4 weeks in the out and in-patient settings for non-specific lung disease. Detailed studies found changed variants of the pathogen as L-forms in 28 (19.4%) patients, bacterial forms being undetectable. The paper shows how difficult to diagnose tuberculosis. PMID- 7984611 TI - [Development of chronic cor pulmonale in restrictive and obstructive pulmonary dysfunctions]. AB - A total of 2840 patients with pulmonary tuberculosis and bronchial asthma were studied. Antigens are shown to induce a systemic vascular response with elevated systolic pressure in the pulmonary artery, peripheral venous spasms. There is activation of the sympathoadrenal system and desensitization of beta adrenoreceptors with lower levels of cyclic adenosine monophosphate (CAMP). There is a direct correlation between the CAMP levels and the cardiac output, between those and the pulmonary systolic pressure (PSP). This determines hyperkinetic hemodynamics in tuberculosis with the volume- and pressure-loaded heart. Paresis of pulmonary circulation, as well as hypokinetic hemodynamics occur as a result of an allergic immunological reaction in severe fibrocavernous processes in the area of tuberculosis. There is a direct correlation between the circulating immune complexes and CAMP. In bronchial asthma microcirculation is impaired due to antigenic exposures and elevated intrathoracic pressure. Pulmonary capillary reduction in restrictive processes results in higher levels of CAMP and right-to left shunt, leading to hypoxemia. In obstructive pulmonary diseases, hypoxemia is caused by hypoventilation and impaired ventilation-perfusion ratios. PMID- 7984612 TI - [Paradoxical respiration in patients with chronic diffuse lung diseases and regional lung rheography for its diagnosis]. AB - The paper shows that some patients with disseminated pneumo- and pleurofibrosis and pulmonary emphysema, which have developed in chronic specific and nonspecific lung diseases, have severe local disorders of respiratory biomechanics, which appear as the paradoxical ventilation phenomenon It also indicates that these abnormalities can be identified by the rather easy-to-use and accessible technique, regional rheography of the lung. The significance of detection of the paradoxical local ventilation phenomenon for clarifying the mechanism responsible for ventilation disorders is illustrated by a clinical note. PMID- 7984613 TI - [Preoperative low energy laser irradiation of the lungs and its effect on prostaglandin and cyclic nucleotide metabolism]. PMID- 7984614 TI - [Comparative evaluation of the methods of reconstructive plastic surgeries for tuberculous arthritis and borderline diseases]. PMID- 7984615 TI - [Effect of tuberculin on the clinical course and healing processes in experimental tuberculosis]. AB - Two procedures for treating experimental tuberculosis were compared. One comprised a rapid administration of tuberculin up to large doses (20,000 TE), the other included weakly stimulating therapy with tuberculin (its maximum dose being 150 TE). Treatment with tuberculin in combination with isoniazid ensures a higher resolution of specific abnormalities than that with isoniazid alone. However, when either procedures were used, the weakly stimulating procedure led to experimental animals' death, which generates the need to take a preliminary account of the body's response to tuberculin in the clinical setting in order to choose tuberculin therapy on an individual basis. PMID- 7984616 TI - [Ultrastructural and radioautographic study of bronchial biopsy in pulmonary tuberculosis during endobronchial laser therapy]. AB - Structural and metabolic changes were explored in 68 main bronchial mucosal biopsy specimens from 31 patients with fibrocavernous pulmonary tuberculosis. It was shown that He-Ne laser endobronchial therapy induced proliferative and metabolic processes (as judged from the level of DNA and RNA syntheses) in the damaged epithelium, which restored its structure and differentiation into celiary and goblet cells with normal ultrastructure having undergone a number of transitional forms. The proliferative and metabolic activity of endotheliocytes and stromal cells increased in the intrinsic layer of the mucosa, which was accomplished by formation of soft fiber connective tissue. PMID- 7984617 TI - [Changes of immune and non-specific reactivity in patients with chronic suppurative obstructive bronchitis in comprehensive treatment with thymogen]. AB - A total of 33 patients with chronic pyoobstructive bronchitis with immunological disorders (of T-cell and other links) and nonspecific responsiveness. The use of thymogen in multi-modality treatment contributed to normalization of T-cell immunity (increases in E-rosette formation, responses of blast cell transformation to phytohemagglutinin, Tx/Tc ratio), as well as nonspecific responsiveness parameters (C3c, NBT-test, natural killers), resulting in higher clinical efficacy. PMID- 7984618 TI - [Quantitative and functional changes of plasma fibronectin in patients with pulmonary tuberculosis]. AB - The plasma levels of immunoreactive fibronectin (IRF) and its functionally full value fraction (FVF) were estimated from the capacity to bind to heparin to form a cold precipitate in 86 patients with various types of active pulmonary tuberculosis on admission, 1, 2-3, and 4-6 months after multimodality treatment. Active pulmonary tuberculosis was found to be accompanied by an acute phasic increase in IRF, which was masked by its increased uptake and regularly detected at early stages of chemotherapy. The levels of FVF sharply dropped. A follow-up of IRF and FVF levels during treatment permits the monitoring of the magnitude of biological effects. PMID- 7984619 TI - [Non-specific resistance of neutrophil granulocytes by cationic protein indices in the development of tuberculosis]. AB - The paper gives cytochemical findings of the lysosomal cationic system of neutrophilic granulocytes in the blood of 188 patients with various pulmonary tuberculoses. In infiltrative pulmonary tuberculosis which was first detected, the decrease in the activity of the lysosomal cationic system of neutrophils was adequate to the extent and severity of the process. The permanent increase in the antimicrobial potential of neutrophilic granulocytes in patients with fibrous and cavernous pulmonary tuberculosis is a defense response of the body, however with constantly progressive tuberculosis, there is inhibition of this defense system, which becomes an unfavourable sign. It can be assumed that the parameters of the activity of bactericidal systems in the neutrophilic granulocytes reflect, to a greater extent, both the activity of this system and the resistance of the whole body. PMID- 7984620 TI - [Lipid peroxidation -- antioxidants -- proteinase inhibitors in osteoarticular tuberculosis]. AB - The multidimensional statistical analysis was used to thoroughly study the status of lipid peroxidation, the antioxidative system and proteolytic inhibitors in 22 patients with an active and 26 with a metatuberculous deforming osteoarticular process. In both cases, enhanced lipid peroxidation is followed by various changes in the systems of endogenous antioxidants and inhibitors of proteolysis. Imbalance of these systems in the active process, unlike the deforming osteoarticular one, requires a differential approach when proteolytic antioxidants and inhibitors are used. PMID- 7984621 TI - [Liver function in patients with aspirin-induced bronchial asthma]. AB - Biochemical and immunological studies were performed to study hepatic function in 137 patients, out of whom 74 were found to have aspirin-induced bronchial asthma, 23 atopic bronchial asthma, 23 infectious allergic bronchial asthma, 17 chronic persistent hepatitis. Cholestatic and hepatodepressive syndromes and hepatic detoxifying and absorptive-excretory dysfunctions were detected in patients with aspirin-induced bronchial asthma. As aspirin-induced bronchial asthma progresses, the rate of hepatobiliary dysfunctions increases, which undoubtedly plays a prominent role in the development of the disease. PMID- 7984622 TI - [Current status and perspectives in hospital treatment of patients with tuberculosis complicated with alcohol abuse]. AB - The authors show a rise in the prevalence of tuberculosis among alcoholics. In the past decade, the specific proportion of these two concurrent diseases has reached 30% among the groups registered in the tuberculosis dispensaries. In a great number of patients, the disease was accompanied by bacterial secretion and decay. The therapeutical efficacy of compulsory treatment inpatients who refuse to take drugs has proved to be low. A daytime hospital can be one of treatments of such patients as the second stage of therapy after tuberculosis patients suffering from alcoholism have stayed in a twenty-four-hour hospital. PMID- 7984623 TI - Where is NMR taking us? PMID- 7984624 TI - Torsion angle dynamics: reduced variable conformational sampling enhances crystallographic structure refinement. AB - A reduced variable conformational sampling strategy for macromolecules based on molecular dynamics in torsion angle space is evaluated using crystallographic refinement as a prototypical search problem. Bae and Haug's algorithm for constrained dynamics [Bae, D.S., Haug, E.J. A recursive formulation for constrained mechanical system dynamics. Mech. Struct. Mach. 15:359-382, 1987], originally developed for robotics, was used. Their formulation solves the equations of motion exactly for arbitrary holonomic constraints, and hence differs from commonly used approximation algorithms. It uses gradients calculated in Cartesian coordinates, and thus also differs from internal coordinate formulations. Molecular dynamics can be carried out at significantly higher temperatures due to the elimination of the high frequency bond and angle vibrations. The sampling strategy presented here combines high temperature torsion angle dynamics with repeated trajectories using different initial velocities. The best solutions can be identified by the free R value, or the R value if experimental phase information is appropriately included in the refinement. Applications to crystallographic refinement. Applications to crystallographic refinement show a significantly increased radius of convergence over conventional techniques. For a test system with diffraction data to 2 A resolution, slow-cooling protocols fail to converge if the backbone atom root mean square (rms) coordinate deviation from the crystal structure is greater than 1.25 A, but torsion angle refinement can correct backbone atom rms coordinate deviations up to approximately 1.7 A. PMID- 7984625 TI - Molecular basis of cooperativity in protein folding. V. Thermodynamic and structural conditions for the stabilization of compact denatured states. AB - The heat-denatured state of proteins has been usually assumed to be a fully hydrated random coil. It is now evident that under certain solvent conditions or after chemical or genetic modifications, the protein molecule may exhibit a hydrophobic core and residual secondary structure after thermal denaturation. This state of the protein has been called the "compact denatured" or "molten globule" state. Recently is has been shown that alpha-lactalbumin at pH < 5 denatures into a molten globule state upon increasing the temperature (Griko, Y., Freire, E., Privalov, P.L. Biochemistry 33:1889-1899, 1994). This state has a lower heat capacity and a higher enthalpy at low temperatures the stabilization of the molten globule state is of an entropic origin since the enthalpy contributes unfavorably to the Gibbs free energy. Since the molten globule is more structured than the unfolded state and, therefore, is expected to have a lower configurational entropy, the net entropic gain must originate primarily from solvent related entropy arising from the hydrophobic effect, and to a lesser extent from protonation or electrostatic effects. In this work, we have examined a large ensemble of partly folded states derived from the native structure of alpha-lactalbumin in order to identify those states that satisfy the energetic criteria of the molten globule. It was found that only few states satisfied the experimental constraints and that, furthermore, those states were part of the same structural family. In particular, the regions corresponding to the A, B, and C helices were found to be folded, while the beta sheet and the D helix were found to be unfolded. At temperatures below 45 degrees C the states exhibiting those structural characteristics are enthalpically higher than the unfolded state in agreement with the experimental data. Interestingly, those states have a heat capacity close to that observed for the acid pH compact denatured state of alpha lactalbumin [980 cal (mol.K)-1]. In addition, the folded regions of these states include those residues found to be highly protected by NMR hydrogen exchange experiments. This work represents an initial attempt to model the structural origin of the thermodynamic properties of partly folded states. The results suggest a number of structural features that are consistent with experimental data. PMID- 7984626 TI - Crystallographic analysis of oxygenated and deoxygenated states of arthropod hemocyanin shows unusual differences. AB - The X-ray structure of an oxygenated hemocyanin molecule, subunit II of Limulus polyphemus hemocyanin, was determined at 2.4 A resolution and refined to a crystallographic R-factor of 17.1%. The 73-kDa subunit crystallizes with the symmetry of the space group R32 with one subunit per asymmetric unit forming hexamers with 32 point group symmetry. Molecular oxygen is bound to a dinuclear copper center in the protein's second domain, symmetrically between and equidistant from the two copper atoms. The copper-copper distance in oxygenated Limulus hemocyanin is 3.6 +/- 0.2 A, which is surprisingly 1 A less than that seen previously in deoxygenated Limulus polyphemus subunit II hemocyanin (Hazes et al., Protein Sci. 2:597, 1993). Away from the oxygen binding sites, the tertiary and quaternary structures of oxygenated and deoxygenated Limulus subunit II hemocyanins are quite similar. A major difference in tertiary structures is seen, however, when the Limulus structures are compared with deoxygenated Panulirus interruptus hemocyanin (Volbeda, A., Hol, W.G.J.J. Mol. Biol. 209:249, 1989) where the position of domain 1 is rotated by 8 degrees with respect to domains 2 and 3. We postulate this rotation plays an important role in cooperativity and regulation of oxygen affinity in all arthropod hemocyanins. PMID- 7984627 TI - Helix-capping interaction in lambda Cro protein: a free energy simulation analysis. AB - The stability mutant Tyr-26-->Asp was studied in the Cro protein from bacteriophage lambda using free energy molecular dynamics simulations. The mutant was calculated to be more stable than the wild type by 3.0 +/- 1.7 kcal/mol/monomer, in reasonable agreement with experiment (1.4 kcal/mol/monomer). Moreover, the aspartic acid in the mutant was found to form a capping interaction with the amino terminus of the third alpha-helix of Cro. The simulations were analyzed to understand better the source of the stability of this helix-capping interaction and to examine the results in light of previous explanations of stabilizing helix caps--namely, a model of local unsatisfied hydrogen bonds at the helix termini and the helix macrodipole model. Analysis of the simulations shows that the stabilizing effect of this charged helical cap is due both to favorable hydrogen bonds with backbone NH groups at the helix terminus and to favorable electrostatic interactions (but not hydrogen bonds) with their carbonyls (effectively the next row of local dipoles in the helix). However, electrostatic interactions are weak or negligible with backbone dipolar groups in the helix further away from the terminus. Moreover, the importance of other local electrostatic interactions with polar side chains near the helix terminus, which are neglected in most treatments of this effect, are shown to be important. Thus, the results support a model that is intermediate between the two previous explanations: both unsatisfied hydrogen bonds at the helix terminus and other, local preoriented dipolar groups stabilize the helix cap. These findings suggest that similar interactions with preoriented dipolar groups may be important for cooperativity in other charge-dipole interactions and may be employed to advantage for molecular design. PMID- 7984629 TI - Crystallization of a scRIP-gelonin isolated from plant seeds Gelonium multiforum. AB - Single crystals of the protein gelonin isolated from the seeds of Gelonium multiforum have been grown at room temperature by vapor diffusion method. The crystals are monclinic with a = 49.4 A, b = 44.9 A, c = 137.4 A, and beta = 98.3 degrees. The space group is P2(1), with two molecules in the asymmetric unit which are related by a noncrystallographic 2-fold axis along psi = 13 degrees and phi = 88 degrees. The crystals diffract X-rays to high resolution, making it possible to obtain an accurate structure of this single chain ribosome inactivating protein. PMID- 7984628 TI - X-ray crystal structure and molecular dynamics simulation of bovine pancreas phospholipase A2-n-dodecylphosphorylcholine complex. AB - The crystal structure of n-dodecylphosphorylcholine (n-C12PC)-bovine pancreas phospholipase A2 (PLA2) complex provided the following structural characteristics: (1) the dodecyl chain of n-C12PC was located at the PLA2 N terminal helical region by hydrophobic interactions, which corresponds to the binding pocket of 2-acyl fatty acid chain (beta-chain) of the substrate phospholipid, (2) the region from Lys-53 to Lys-56 creates a choline-receiving pocket of n-C12PC and (3) the N-terminal group of Ala-1 shifts significantly toward the Tyr-52 OH group by the binding of the n-C12PC inhibitor. Since the accuracy of the X-ray analysis (R = 0.275 at 2.3 A resolution) was insufficient to establish these important X-ray insights, the complex structure was further investigated through the molecular dynamics (MD) simulation, assuming a system in aqueous solution at 310K. The MD simulation covering 176 ps showed that the structural characteristics observed by X-ray analysis are intrinsic and also stable in the dynamic state. Furthermore, the MD simulation made clear that the PLA2 binding pocket is large enough to permit the conformational fluctuation of the n-C12PC hydrocarbon chain. PMID- 7984630 TI - Crystallization and preliminary X-ray diffraction studies of mandelonitrile lyase from almonds. AB - Single crystals of three different isoenzymes of (R)-(+) mandelonitrile lyase (hydroxynitrile lyase) from almonds (Prunus amygdalus) have been obtained by hanging drop vapor diffusion using polyethylene glycol 4000 and isopropanol as co precipitants. The crystals belong to the monoclinic space group P2(1) with unit cell parameters a = 69.9, b = 95.1, c = 95.6 A, and beta = 118.5 degrees. A complete set of diffraction data has been collected to 2.6 A resolution on native crystals of isoenzyme III. PMID- 7984631 TI - Regional ethnopharmacology: Turbina corymbosa (L.) Raf. PMID- 7984632 TI - Heparin-induced thrombocytopenia. PMID- 7984633 TI - Nitric oxide suppression of norepinephrine release from nerves in the superior mesenteric artery. PMID- 7984634 TI - Cytokine studies in allergy and asthma. PMID- 7984635 TI - Release of an alkylating metabolite, dehydromonocrotaline, from the isolated liver perfused with the pyrrolizidine alkaloid, monocrotaline. PMID- 7984636 TI - Relationship between in vitro metabolism of pyrrolizidine alkaloids and extrahepatic toxicity in vivo. PMID- 7984637 TI - The effects of oxytocin and acetylcholine on the uterine smooth muscle fibers of pregnant rats at term with pelvic neurectomy. PMID- 7984638 TI - Ultrastructural alterations in the Sertoli cells of adult mice exposed to diazepam. PMID- 7984639 TI - Cerebellar ultrastructural changes produced by diazepam. PMID- 7984640 TI - Comparative study of ketorolac and dipyrone administered orally in the treatment of postoperative pain. PMID- 7984641 TI - Serotonin may affect hepatic glycogen stores in rats. PMID- 7984642 TI - Effect of para-chlorophenylalanine on brain concentration of monoamines in a bird species. PMID- 7984643 TI - Open study to evaluate the efficacy and safety of intramuscular naproxen in flares of different rheumatic condition. PMID- 7984644 TI - Direct cardiac effects of droperidol and thiopental. PMID- 7984645 TI - Naloxone prevents reduction of pain responses evoked by acupuncture in neuropathic rats. PMID- 7984646 TI - Cross-substitution of diazepam for barbital results in only a low incidence of audiogenic seizures upon withdrawal in dependent rats. PMID- 7984647 TI - Neurochemical quality of nonopioid stress-induced analgesia is not altered by estrous phase in female mice. PMID- 7984648 TI - Anticancer activity of Morinda citrifolia (noni) on intraperitoneally implanted Lewis lung carcinoma in syngeneic mice. PMID- 7984649 TI - Comparison of intravenous ketorolac and butorphanol on ventilatory function and analgesia of pain after surgery. PMID- 7984650 TI - Effect of parachlorophenylalanine on sleep spikes in the iguanid lizard Ctenosaura pectinata. PMID- 7984651 TI - Adenosine metabolism in vivo. PMID- 7984652 TI - Single blind study to evaluate the efficacy and safety of naproxen gel compared with diclophenac emulgel in the treatment of soft tissue injuries. AB - Sixty four adult patients of both genders with injuries such as contusions and sprains were studied. Of these, 34 were treated with 10% naproxen gel and 30 with 1% dichlophenaco gel topically given for 4 days. Various pain modalities, edema and functional alterations of areas involved were studied. Naproxen reduced spontaneous pain slightly better than dichlophenaco. Both drugs resulted in significant reduction of other pain modalities, edema and functional alterations (p < 0.001). A lower percentage (29%) of naproxen patients used paracetamol as additional pain reliever compared to dichlophenaco patients (36%). Local adverse events were minimum for both groups. PMID- 7984653 TI - Symptomatic treatment of common cold in children with a new combination of naproxen sodium plus pseudoephedrine hydrochloride: a comparative trial against pseudoephedrine syrup. PMID- 7984654 TI - Enhancement of striatal lipid peroxidation induced by 1-methyl-4-phenylpyridinium in mouse brain is blocked by MAO-B inhibitors. PMID- 7984655 TI - Bioequivalence study of a new combination of naproxen sodium plus pseudoephedrine capsules in a Mexican sample population. PMID- 7984656 TI - Alpha 1-adrenoceptors: pharmacological subclassification and therapeutic applications. PMID- 7984657 TI - Analgesic interactions produced by combinations of dipyrone and morphine in the rat. PMID- 7984658 TI - Bi-directional control of smooth muscle tension: regulation by tyrosine kinase and tyrosine phosphatase. PMID- 7984659 TI - Mediation of 5-hydroxytryptamine-induced decrease in external carotid blood flow in the dog by 5-HT1-like receptors and a receptor unrelated to the 5-HT1, 5-HT2, 5-HT3 or 5-HT4 types. PMID- 7984660 TI - Anitumoral effect of thallium against N-ethyl-N-nitroso-urea-induced brain tumors. PMID- 7984661 TI - Kynurenine and probenecid prevent quinolinic acid-induced neurotoxicity in rat corpus striatum. PMID- 7984662 TI - Effects of doxycycline in two rat models of ischemia/reperfusion injury. PMID- 7984663 TI - Acetylcholine relaxes the human umbilical artery by an endothelium-independent but ouabain and tetraethylammonium-sensitive process. PMID- 7984664 TI - Compartmentation of NADPH-diaphorase activity in the anterior lobe vermis of the mouse cerebellar cortex. PMID- 7984665 TI - Insulin resistance produced by hepatic denervation or muscarinic cholinergic blockade. PMID- 7984666 TI - Analysis of the cardiodepressor action of 3-nitropropionic acid. PMID- 7984667 TI - Comparison of cobalt edetate and alpha-ketoglutarate as antidotes against cyanide intoxication in mice. PMID- 7984668 TI - Role of vascular endothelium on contractile and pressor responses induced by imidazole-derived alpha-adrenergic agonists. PMID- 7984669 TI - Role of central serotoninergic neuronal systems and the hypothalamic-pituitary thyroid axis in mediating thermogenic effects of thyrotropin-releasing hormone in long-sleep and short-sleep mice. PMID- 7984670 TI - Acute cardiovascular and toxic effects of potassium channel blockers in anesthetized primates. PMID- 7984671 TI - Candida in patients of a surgical intensive care unit. PMID- 7984672 TI - Neuropeptide modulation of cardiac intrinsic nerve activity: neuropeptide Y--a preliminary report. PMID- 7984673 TI - Glutamate agonists evoke glycine release from hippocampal slices from developing mice. PMID- 7984674 TI - Thiol reagents and brain glutamate receptors. PMID- 7984676 TI - Sexual activity in male mice treated prenatally with diazepam. PMID- 7984675 TI - Dapsone administration prevents quinolinate-induced neurotoxicity in rats. PMID- 7984677 TI - Mating behavior of female mice treated prenatally with diazepam. PMID- 7984679 TI - The time course of up-regulation and down-regulation of dihydropyridine binding sites during the development of physical dependence on ethanol. PMID- 7984678 TI - Stress-induced changes in gastrointestinal transit in mice are dependent on gender. PMID- 7984680 TI - Felbamate: interaction with glycine receptors in human cerebral cortex. PMID- 7984681 TI - Influence of Mexican diet on nifedipine pharmacodynamics in healthy volunteers. PMID- 7984682 TI - Phosphodiesterase inhibitors have differential effects on placental versus decidual prorenin release. PMID- 7984683 TI - Haloperidol increases pain behavior following peripheral tissue injury. PMID- 7984684 TI - Vasodilator and hypotensive effects of droperidol. PMID- 7984685 TI - Relationship between plasma levels of naproxen and analgesic efficacy in rats: synergism with caffeine. PMID- 7984686 TI - Canine external carotid vasoconstriction induced by 2-(2-aminoethyl)quinoline (D 1997), a novel agonist at vascular 5-HT1-like receptors. PMID- 7984687 TI - Effects of propofol and thiopental on patient recovery from anesthesia. PMID- 7984688 TI - Systemic absorption of lidocaine via canine carotid artery. PMID- 7984689 TI - Pharmacological and surgical management of pediatric renal injuries. PMID- 7984690 TI - Molecular biological perspectives in treating neuropsychiatric disorders with dopaminergic drugs. AB - This review aims to present perspectives of molecular neuropharmacology in the development of more targeted drugs that modulate dopaminergic functions in various neuropsychiatric disorders. Recent advances in molecular neurobiology have revealed five distinct dopamine receptor (DR) genes and multiple allelic variations encoding DR subtypes with functional diversity. Depending on the different biophysical and pharmacological properties and the various cerebral distributions of the DR subtypes, the action profile of subtype-specific dopaminergic drugs can be predicted. In vitro expression of DR gene variants in mammalian cell lines will facilitate the screening and pharmacological characterization of dopaminergic ligands. Molecular modeling of the DR subtypes by three-dimensional computer models will be useful for establishing structure function relationships between ligands and the DRs, and could provide a template for the design of receptor-specific drugs. In the near future, drugs modulating dopamine turnover and transport or involving the successive effector systems will increase the current therapeutical spectrum. PMID- 7984691 TI - Nerve growth factor: pathophysiological and therapeutic implications. AB - Neurotrophic factors are target-derived proteins capable of affecting survival, target innervation, and/or function of neuronal cell populations. Nerve growth factor (NGF) is the best-studied member of the genetic family called neurotrophins. There is however little knowledge whether other neurotrophins play a pathophysiological role in diseases of the peripheral and central nervous system. An increasing number of animal studies suggest that NGF plays a role in (a) peripheral nerve regeneration, (b) diabetic neuropathy, and (c) age-related neurodegenerative processes within the brain. PMID- 7984692 TI - Multidimensional assessment of acute and long-term effects in antidepressant drug trials. AB - Contrasting the findings from pharmacoepidemiological studies with the status of registration of new compounds and the legal process of reviewing the old compounds indicates a crisis of the preclinical and clinical investigations of "antidepressants". Within the last two decades, the development of more and more formalized guidelines and regulations for the performance of clinical drug trials could be observed. Certainly, this has resulted into an improved internal validity of the findings. On the other hand, there appears to be a broad consensus among practising psychiatrists that published findings of clinical trials often do not concur with the experiences of psychiatric practice indicating unsatisfactory external validity. With regard to the aim of optimizing the antidepressant therapy and to lower the costs for mental health care, it appears to be of particular importance to test the real effectiveness of an "antidepressant" as close as possible to its use in practice. (To avoid misunderstandings: This does not mean to ask for more so-called "naturalistic" study designs!) It is self-evident that also in the future controlled studies, particularly vs. placebo, cannot be dispensed with. However, more promising for a relevant assessment of old and new substances would be the use and development of suitable mathematical procedures, which might imply re-evaluations and re classifications of already published findings; furthermore, it seems essential also to integrate the existing experiences of psychiatrists in hospitals and in private practice.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7984693 TI - Neurobiology of psychotropic drugs: modes of action and therapeutic efficacy. PMID- 7984694 TI - Relapse prevention in alcoholics with an anticraving drug treatment: first results of the Berlin Study. AB - Lisuride--a compound with mainly dopamine d2-agonistic, but also dl-antagonistic and serotonergic properties was choosen in 1.0 mg daily dose as an anticraving drug for keeping alcoholics abstinent who had been included in a randomized double-blind placebo-controlled trial for 6 months. Preliminary results indicate that in the first 55 recruited patients the overall abstinence-rate dropped from 85% after 3 months to 47% after 6 months. Predictors of relapse were early onset of alcohol-related problems, a high number of preceding detoxification and rehabilitation treatments, intermittant drinking habits, less feeling of guilt and low harm avoidance in the TPQ by Cloninger. More details will be given after completing the study when the code is lifted. PMID- 7984695 TI - Electroencephalographic response prediction of antipsychotic drug treatment in acutely ill patients and of long-term prophylactic treatment with lithium salts. AB - The use of the EEG as a pharmacotherapeutic response predictor is still hampered by the largely unsolved problem of extracting the relevant information from the recording in a theory-guided manner and by the likewise largely underestimated fact of pathobiological heterogeneity in diagnostically homogenous groups of patients. Instead of the usual group-statistical designs that rely solely on homogenous psychopathology, we advocate a strategy of single case studies, performed as comprehensive as possible and giving special attention to the baseline condition. It is only a certain number of such single case studies that afford an empirical data base for meaningfully applicating statistical procedures. PMID- 7984696 TI - Evoked potentials, serotonin, and suicidality. AB - The link between suicidality and serotonergic dysfunction is a consistent finding in biological psychiatry. In three independent studies we found weak intensity dependence of auditory evoked potentials, which may be related to high serotonergic activity, in psychiatric patients with a history of suicide attempts. This result seems to contradict studies reporting low serotonergic activity in acute suicidal patients. As an explanation for this discrepancy we propose that serotonergic activity may be low only in acute suicidal states, and that high serotonergic activity, as reflected by a weak intensity dependence, may characterize high-risk patients, in whom a transient decrease of serotonergic activity is accompanied by acute suicidality. PMID- 7984697 TI - Psychopathology and the analysis of therapeutic effects. AB - The different domains of psychopathological research are described. An example of taxonomies that may be relevant for therapy is given. For the apathy scale of the AMDP system it is demonstrated that there is an equivalent severity of this syndrome in acute paranoid hallucinatory schizophrenia and in unipolar depression. In schizophrenia the apathy syndrome may subsume some, if not all, of the negative symptoms, that cause major problems for therapy. A common pathophysiological factor for the syndrome in the two diseases is discussed. A systematic psychopathological approach to the identification of pathophysiological factors of drug effects and their involvement in psychiatric diseases, including experimental variables, is characterized. PMID- 7984698 TI - Implications of the concepts "coping" and "quality of life" for criteria of course and outcome. AB - The Berlin Coping Study is a prospective longitudinal project with schizophrenic patients investigating the relationship between coping strategies and course and outcome. We find that some psychological issues relevant for both clinical practice and psychiatric research, and especially for pharmacological therapy, have been rather neglected up to now. The investigation of coping strategies leads to accentuating the patients' subjective individual views concerning their demands, goals, and coping activities in daily living and their schizophrenic illness. The concept of quality of life is increasingly receiving attention in various domains of professional care and it is very relevant to the issues discussed here. Consequences of this approach for therapy and research are outlined. PMID- 7984699 TI - Reduced mortality, the ultimate indicator of treatment efficacy. Review and perspectives. AB - Since psychiatric patients are at risk for increased mortality, one of the strongest indicators of treatment efficacy is a normalized mortality. The question arises as to whether it is possible to change the mortality by different treatment strategies. Surprisingly, intervention studies using death or survival as an endpoint are relatively rare in psychiatry, although in other medical disciplines this approach is very common. A review of the few existing investigations of the influence of somatic therapy on mortality--these mainly relate to affective disorders--suggests that in principle adequate somatic treatment can reduce the high mortality risk in these disorders. A reduced mortality can be observed, particularly during long-term lithium treatment. The question to what extent a somatic therapy can protect psychiatric patients against premature death cannot be answered in a one-dimensional way. There are various factors that can strengthen or weaken the possible benefits of drug therapy. Such influencing factors are the patient, the physician, and the treatment setting. Mortality studies are important to identify the individual factors that influence treatment efficacy. With reference to the role of the moderating variables, the aims of future research in the area of treatment efficacy in psychiatry will be addressed. PMID- 7984700 TI - 5-HT uptake in platelets of lithium-treated patients with affective disorders and of healthy controls. AB - There is strong evidence that platelet 5-HT uptake is reduced during depressive illness, yet it is an open question whether this abnormality can be reverted to normal by successful treatment. The effect of longterm lithium treatment (> 2 years of continuous therapy) on 5-HT uptake of 37 euthymic affective patients without relevant additional medication was investigated. There was no difference in 5-HT uptake kinetics between the whole group of patients and age- and sex matched healthy controls. The subgroups of unipolar patients and patients with minor recurrences during prophylaxis tended to have lower Vmax values of 5-HT uptake. The results generally support the hypothesis of a relationship between successful lithium treatment and normalization of 5-HT uptake. PMID- 7984701 TI - Therapeutic standards in psychopharmacology and medical decision-making. AB - Treatment surveys regularly show deviations of routine treatment from treatment guidelines. An analysis of the scientific basis of classical treatment standards, as derived from controlled treatment trials, shows that they do not take into account many variables with major impact on routine treatment. A better theoretical framework for understanding medical decision-making under complex stimulus conditions is provided by action theory. Studies that test treatment strategies instead of treatments and field observational studies, for both of which examples are given, are necessary adjuncts to controlled clinical trials in the quest for more scientifically based treatment guidelines. PMID- 7984702 TI - Quality assurance in psychiatric care--the example of routine use of the AMDP system. AB - Quality assurance and continuous monitoring of the quality of delivered care in mental health are going to become a topic of increasing importance. There are several reasons for this process, including increased costs for medical treatment, enhanced possibilities of comparing treatment and outcome success by reimbursement agencies, but also evidence from clinical and epidemiological research of differences in clinical practice that cannot be explained by the current state of psychiatric knowledge. The definition of standards of care and of criteria to indicate the quality of delivered care is a topic of current debate. It is shown that indicators for continuous quality assurance monitoring can be derived from systematized routine psychiatric documentation of patients as in the AMDP system, although this system does not provide comprehensive information to cover the full range of indicators necessary to establish sufficient control for quality of care. Future developments are discussed. PMID- 7984703 TI - Structure and feasibility of a standardized stepwise drug treatment regimen (SSTR) for depressed inpatients. AB - "Standardized stepwise treatment regimes" (SSTR) are one way to rationally guide treatment in cases where the first treatment intervention did not yield satisfactory results. At the Department of Psychiatry of the Free University of Berlin a SSTR has been implemented into routine drug treatment for depressive disorders. The SSTR consists of eight consecutive treatment steps. If there is no sufficient change in the Bech-Rafaelsen Melancholy Scale (< 25% score reduction) in the course of two weeks, treatment has to progress to the next step. This paper describes the overall feasibility and efficacy of the strategy and the progress of the patients within the SSTR. Of those who enter the "antidepressant monotherapy phase" 52% finish treatment successfully at this stage or during the following "lithium augmentation phase". The results of this treatment-monitoring study also show that during consecutive phases of the SSTR a considerable proportion of patients in a university inpatient setting had their treatment modified according to special attitudes and clinical experiences of physicians and patients. The reasons for deviating from the SSTR obviously were more convincing than the rationale for progressing to the next step. SSTR, therefore are an important tool to give complex treatment courses a rational basis, even in patients where clinical case management requires deviations from the outlined sequence of treatment steps. PMID- 7984704 TI - Clinical recognition and drug treatment of depression in cases found by standardized assessment. AB - The determination of need of care is an important problem for public health. In an epidemiological perspective the question is whether the right people get the right treatment. The answer depends on a variety of methodological issues such as case-definition, case-identification, sampling, and treatment assessment. Case definition is done by patients themselves and by experts such as physicians or scientists. This study compares the clinical approach of family physicians with the standardized approach of epidemiologists. In two epidemiological studies, the Berlin Aging Study (BASE) and the WHO Study on Psychological Problems in General Health Care (WHO/PPGHC), diagnosis and treatment of major depression in the field were analyzed. In spite of different methods, both studies showed a high rate of unrecognized major depressions as defined by DSM-III-R criteria. This lack of case-recognition by the primary care physicians corresponds to the fact that less than then percent of these patients were treated with antidepressants and none of them had been seen by a psychiatrist. The question to be discussed is whether these results speak for an underrecognition of cases that are in need of care under clinical conditions or an inflation of the respective numbers by standardized methods. PMID- 7984706 TI - Anhedonia in schizophrenic, depressed, or alcohol-dependent patients- neurobiological correlates. AB - Anhedonia, dysphoria, and avolition are common symptoms of schizophrenic, depressive, and alcohol-dependent patients during withdrawal. These symptoms may be caused by a functional deficit of dopaminergic transmission in the dopaminergic reward system, ascending from the mesencephalon to the ventral striatum (nucleus accumbens). The dopaminergic reward system is functionally and anatomically closely connected with the ascending extrapyramidal pathways from the substantia nigra to the dorsal striatum. A dysfunction of both ascending dopaminergic pathways is therefore expected to cause both psychomotor slowing and dysphoria and anhedonia. This hypothesis is supported by PET and SPECT findings, which show that a reduced striatal density of unoccupied dopamine D2-receptors is correlated with extrapyramidal side-effects in neuroleptic-treated schizophrenics and with craving and dysphoria in drug-dependent patients. In order to further investigate the correlation of anhedonia, psychomotor slowing, and the status of the dopaminergic reward system, the density of striatal dopamine D2-receptors can be measured by IBZM-SPECT and related to psychomotor slowing and anhedonia in different states of schizophrenic, depressive, and alcohol-dependent patients. PMID- 7984707 TI - Nature-nurture reconceptualized in developmental perspective: a bioecological model. AB - In response to Anastasi's (1958) long-standing challenge, the authors propose an empirically testable theoretical model that (a) goes beyond and qualifies the established behavioral genetics paradigm by allowing for nonadditive synergistic effects, direct measures of the environment, and mechanisms of organism environment interaction, called proximal processes, through which genotypes are transformed into phenotypes; (b) hypothesizes that estimates of heritability (e.g., h2) increase markedly with the magnitude of proximal processes; (c) demonstrates that heritability measures the proportion of variation in individual differences attributable only to actualized genetic potential, with the degree of nonactualized potential remaining unknown; (d) proposes that, by enhancing proximal processes and environments, it is possible to increase the extent of actualized genetic potentials for developmental competence. PMID- 7984708 TI - Similarity and discrimination: a selective review and a connectionist model. AB - The 1st part of this article evaluates the extent to which 2 elemental theories of conditioning, stimulus sampling theory and the Rescorla-Wagner (1972) theory, are able to account for the influence of similarity on discrimination learning. A number of findings are reviewed that are inconsistent with predictions derived from these theories, either in their present form or in various modified forms. The 2nd part of the article is concerned with developing an alternative, configural account for discrimination learning. In contrast to previous configural theories, the present version is set within the framework of a connectionist network. PMID- 7984709 TI - The triangle model of responsibility. AB - Responsibility acts as a psychological adhesive that connects an actor to an event and to relevant prescriptions that should govern conduct. People are held responsible to the extent that (a) a clear, well-defined set of prescriptions is applicable to an event (prescription-event link); (b) the actor is perceived to be bound by the prescriptions by virtue of his or her identity (prescription identity link); and (c) the actor is connected to the event, especially by virtue of appearing to have personal control over it (identity-event link). Studies supported the model, showing that attributions of responsibility are a direct function of the combined strengths of the 3 linkages (Study 1) and that, when judging responsibility, people seek out information that is relevant to the linkages (Study 2). The model clarifies prior multiple meanings of responsibility and provides a coherent framework for understanding social judgment. PMID- 7984710 TI - Levels of perceptual representation and process in lexical access: words, phonemes, and features. AB - Three experiments and a simulation study investigate competing featural and phonemic views of the representation of the speech input in access to the mental lexicon. Auditory lexical decision and gating tasks show that the processing consequences of subcategorical mismatches (conflicts between phonetic cues to speech segment identity) depend on the lexical status of the conflicting cues, such that conflicts that only involve nonwords do not disrupt performance. A further study, using a phonetic-decision task with the same stimuli, found the same pattern. A simulation study shows that the interactive activation model TRACE, with top-down feedback to a prelexical phonemic level, does not model these effects successfully. The authors argue instead for a direct access featural model, based on a distributed computational substrate, where featural information is mapped directly onto lexical representations. PMID- 7984711 TI - The lexical nature of syntactic ambiguity resolution [corrected]. AB - Ambiguity resolution is a central problem in language comprehension. Lexical and syntactic ambiguities are standardly assumed to involve different types of knowledge representations and be resolved by different mechanisms. An alternative account is provided in which both types of ambiguity derive from aspects of lexical representation and are resolved by the same processing mechanisms. Reinterpreting syntactic ambiguity resolution as a form of lexical ambiguity resolution obviates the need for special parsing principles to account for syntactic interpretation preferences, reconciles a number of apparently conflicting results concerning the roles of lexical and contextual information in sentence processing, explains differences among ambiguities in terms of ease of resolution, and provides a more unified account of language comprehension than was previously available. PMID- 7984712 TI - The role of probability of reinforcement in models of choice. AB - A general account of choice behavior in animals, the cumulative effects model, has been proposed by Davis, Staddon, Machado, and Palmer (1993). Its basic assumptions are that choice occurs in an all-or-none fashion for the response alternative with the highest probability of reinforcement and that the probability of reinforcement for each response alternative is calculated from the entire history of training (total number of reinforced responses/total number of reinforced and nonreinforced responses). The model's reliance on probability of reinforcement as the fundamental variable controlling choice behavior subjects the cumulative effects model to the same criticisms as have been directed toward other related models of choice, notably melioration theory. Several different data sets show that the relative value of a response alternative is not predicted by the obtained probability of reinforcement associated with that alternative. Alternative approaches to choice theory are considered. PMID- 7984713 TI - Cumulative effects model: a response to Williams (1994) AB - The cumulative effects (CE) model explains free-operant choice by the ratio of total numbers of responses and reinforcements, a probability-like variable. Williams (1994) argues that the model is vulnerable to experiments that disprove melioration, a local probability model. The authors note critical differences between the nonlocal CE model and local probability models that allow the CE model to handle some data with which they are incompatible. All models are simplifications of reality; hence, a model's failures are as revealing as its successes. Williams suggests that simple models may need to be abandoned in favor of a "representational" account. The authors point out that representations must be both acquired and acted on. Acquisition requires processing of responses and reinforcers; action requires decision rules. Models are simply testable suggestions for what these rules and processes might be. PMID- 7984714 TI - Propositional reasoning by mental models? Simple to refute in principle and in practice. AB - Two experiments compared the predictions of mental-models theory with a mental logic theory. Results show that people do not make fallacious inferences predicted by mental-models theory but not predicted by mental-logic theory and that people routinely make many valid inferences predicted by mental-logic theory that should be too difficult on mental-models theory. Thus, the mental-logic theory accounts better for the data. A difference between the two theories concerning predictions about the order in which inferences are made was also investigated. The data clearly favor the mental-logic theory. It is argued that the mental-logic theory provides the more plausible description of the actual psychological processes in propositional reasoning. PMID- 7984715 TI - Religious nonaffiliation in relation to suicide, murder, rape, and illegitimacy. PMID- 7984716 TI - On the relationship of the five-factor personality model to personality disorders: four reservations. AB - McCrae and Costa since 1986 have proferred a five-factor personality model as a lingua franca among different psychometric test users, and they suggest that their operationalization of the five-factor model, the NEO Personality Inventory, may also be useful in the clinical assessment of the abnormal personality. The present study examined the inventory and its relationship to the 11 personality disorders of Axis II of DSM-III-R in a sample of 180 adults. Correlational multivariate analyses appear to indicate a limited usefulness of the five-factor model in the understanding of personality disorders, and four major objections are offered. Further research with clinical samples, other models of personality, and other measures of personality disorders are encouraged. PMID- 7984718 TI - Assertiveness and personality dimensions in Chinese students. AB - In a Chinese sample of 208 the Big Five personality traits profile was compared for 104 assertive and 104 nonassertive students. While assertiveness was associated with higher scores on Neuroticism, Extraversion, and Openness, Nonassertiveness was associated with greater scores on Agreeableness and Conscientiousness. Implications of the findings for cross-cultural counselling were highlighted. PMID- 7984717 TI - Correlation between depression and vision in aged patients before and after cataract operations. AB - To investigate the association between depression and vision, 100 cataract operation patients (25 were men and 75 women) aged 71 to 76 years were studied. One day before the operation and 3 mo. after, the patients' depression was tested with the short form of the Beck Depression Inventory and their personalities with Mini-Mult MMPI. The cataract operation restored visual acuity sufficient for reading (minimum E-test value 0.40) to 79% of the subjects. The analysis indicated that their depression was significantly correlated with vision only after the cataract operation. Depression increased with weakened visual acuity and diminished with improved visual acuity. Part of the postoperation depression was, however, associated with glaucoma and serious somatic diseases (asthma, cerebrovascular disorders, and heart diseases). PMID- 7984719 TI - Could popping air capsules affect state anxiety? AB - The present study examined whether popping air capsules affects students' state anxiety. One group of university students were asked to pop air capsules for 5 min. (experimental group); another group did nothing (the control group). Both groups were tested on the State-Trait Anxiety Inventory. Analyses showed that there was a difference in mean State Anxiety scores between the two groups, with the control group having a lower mean than the experimental group, which was contrary to our expectation. The findings are discussed in relation to an earlier published study of the effects of popping air capsules on changing a person's mood. PMID- 7984720 TI - Another femininity scale? AB - The construction and validation of the Behavioral Self-report of Femininity is described. An initial sample of 32 male and 63 female undergraduates indicated the frequency of engaging in 91 "feminine" behaviors. The 59 items which showed good internal consistency as well as differentiation between genders were retained. Test-retest reliability over a 2-wk. period was .90. Convergent and discriminant validities were examined by comparing our results with those obtained from the Hyperfemininity Scale and the Personal Attributes Questionnaire. Responses of women in traditional and nontraditional majors were significantly different, indicating good within-sex validity. Finally, a principal components analysis identified six primary factors, accounting for 60% of common variance. PMID- 7984721 TI - On the prediction of aggressive behavior from the Rorschach. AB - Research on predicting aggressive or hostile behavior from the Rorschach was reviewed. This overview suggested that the propensity for acting aggressively or in a hostile manner seemed less related to the quantity or quality of aggressive content than to indicators of impoverished control, e.g., CF+C > FC, F + % < 70, what some Rorschachers refer to as 'ego control.' However, methodological issues in the research on content which could have compromised these results were also discussed as was the kind of research still needed. PMID- 7984722 TI - Perceptions of parents' involvement in learning and adolescents' aspirations. AB - Commonality analysis was used to examine relationships between global and perceived measures of parents' involvement in learning and the aspirations of 516 16-yr.-old Australians. Analysis indicated that, while adolescents' perceptions of parents' involvement had strong associations with their aspirations, such relationships should be examined within environmental contexts assessed by more global measures of parents' involvement. PMID- 7984723 TI - Education students' overestimation of the prevalence of learning disabilities. AB - A number of studies have suggested that educators overestimate the prevalence of learning disabilities in the schools. In this study, we found that 339 first- and second-year education students estimated the prevalence of learning disabilities to be four times higher than the upper limits of prevalence established by experts. Given that mislabelling students as 'learning disabled' may have negative consequences for them, the meaning, etiology, and prevalence of students' learning problems should be addressed by training institutions. PMID- 7984724 TI - Time pressure, type A syndrome, and organizational citizenship behavior: a laboratory experiment. AB - Time pressure was manipulated in a laboratory task for 77 undergraduate subjects, who also responded to a measure of Type A syndrome. Afterwards, an occasion for organizational citizenship behavior was presented in the form of participation in a survey. Type A scores were unrelated to those on any measure of organizational citizenship behavior; time pressure acted to depress especially the quality of organizational citizenship behavior. PMID- 7984725 TI - Question effects on question generation and the mediation of attitude change. AB - 80 undergraduates were exposed to arguments advocating supplemental vitamin use. Ending arguments with rhetorical questions (when compared with statements) resulted in more favorable attitudes towards vitamin use and a more favorable profile of questions generated about the message topic. The question profile, principally reflecting uncertainty concerning personal nutrition, mediated the attitudinal effect. PMID- 7984726 TI - Sequoia over Hemlock: life termination's noniatrogenic third alternative. AB - The choice to die with or without dignity based on medical opinion is a restricted field. A third option of not dying at all or at least attempting this outcome via new physicians is proposed. PMID- 7984727 TI - Alexithymia and defense mechanisms in myocardial infarction. AB - The relationship between alexithymia and defense mechanisms was examined among 66 patients with myocardial infarction. Alexithymia was greater among patients with acute myocardial infarction than among those with old myocardial infarction. Alexithymia was correlated with scores on measures of the defense mechanisms of denial, negation, repression, and reaction formation. The results suggest the possibility that alexithymia may be evident when effective coping mechanisms are employed to minimize the severity of perceived threats or conflicts. PMID- 7984728 TI - Bulimic symptomatology and personality factors in a nonclinical sample: a replication. AB - Analysis of 102 undergraduate women's responses replicated the 1993 findings of Janzen, Saklofske, and Kelly considering the relationship between personality characteristics based on the Eysenck Personality Questionnaire--Revised and bulimic symptomatology as measured by the BULIT--R. Consistent with Janzen, et al., the strongest relationship with bulimic symptomatology was for Neuroticism. Also consistent was the lack of relationship with Extraversion scores. At variance with the earlier findings was a weak positive association between reports of bulimic symptoms and scores on Psychoticism. PMID- 7984729 TI - Thought suppression and obsession-compulsion. AB - It was argued that obsession-compulsion might affect the consequences of thought suppression. A group of 35 female students who were first submitted to thought suppression and then to an expression instruction were compared with a group of 38 female students submitted twice to an expression instruction. The emotional character of a target story read by subjects was systematically varied between subjects, and obsession-compulsion was included as a third between-subjects factors. No evidence of rebound or of initial enhancement was found when reported story-related thoughts were compared across instructional conditions. There was an interaction between obsession-compulsion and initial instruction on attempts to avoid target thoughts during the first period. Contrary to expectations obsession-compulsion was related to fewer attempts at suppression in the suppression and more in the expression conditions. Similarly, there was a trend for obsession-compulsion to be related to more frequent target thoughts in the expression and less in the suppression conditions. These findings are discussed in relation to the role of perceived responsibility in obsession-compulsion for thought as a determinant of thought processes of obsessive-compulsive people. PMID- 7984730 TI - Internalized homophobia and psychosexual adjustment among gay men. AB - The present study examined links between internalized homophobia and psychosexual tendencies among 261 homosexual men. Analysis indicated that men who accept their homosexuality less rate themselves higher on sexual anxiety, sexual depression, fear of sexuality, and concern about sexual image and lower on internal sexual control, sexual esteem, and sexual satisfaction. Although no significant differences were found between HIV-seropositive and HIV-seronegative subjects, the associations between internalized homophobia and certain psychosexual tendencies seemed more pronounced in the seropositive respondents. We believe it would be beneficial for homosexual men who are very homophobic to seek psychoeducative or therapeutic consultation to develop more positive attitudes toward their homosexuality and thereby better the quality of their lives. PMID- 7984731 TI - Affective reactions to employment and unemployment as a function of prior expectations and motivation. AB - Self-esteem and depressive affect measures were obtained from 809 employed and 137 unemployed young people and compared with at-school measures taken three years earlier. Scores were analysed in relation to at-school expectations of obtaining employment and expressed importance of getting a job. In both employed and unemployed groups, low prior expectations of getting a job led to a greater increase in self-esteem than high prior expectations. Among the unemployed, those who had rated getting a job as relatively important showed a greater increase in depressive affect than those who had rated getting a job as relatively less important. PMID- 7984732 TI - Convergent validation of the Illness Effects Questionnaire. AB - The Illness Effects Questionnaire, Illness Behavior Questionnaire, and visual analog scales of mood were given to 100 adults with nonmalignant headaches. Using regression analysis, scores on IBQ Disease Conviction, IBQ Irritability, and depression accounted for 50.6% of the variance in predicting IEQ scores. Scores on the Illness Effects Questionnaire correlated with the Illness Behavior Questionnaire subscales of General Hypochondriasis (.33), Disease Conviction (.60), Affective Disturbance (.49), and Irritability (.40), and also with rated depression (.38) and anxiety (.26). PMID- 7984733 TI - Correlates of hysterical symptoms in schizophrenic patients. AB - The correlations of symptoms of hysteria with 87 symptoms relevant for diagnosing schizophrenia were examined in a sample of 112 patients (70 women and 42 men whose mean age was 38.1 yr., SD = 9.8) with DSM-III diagnosis of schizophrenia. Hysterical symptoms were recorded in 37.5% of the schizophrenics. No significant relationships (phi coefficients) were found to key symptoms of schizophrenia. PMID- 7984734 TI - Using incentives to promote workers' participation in worksite research. AB - We designed this study to examine the effects of two types of incentives on the participation rate of workers from two plants in worksite research. There were 186 workers in the study, some of whom received chances for savings bonds. Given reductions in funding and concerns of management, no comparison could be made between the incentives; however, the study provided valuable information regarding planning for incentives in worksite research. PMID- 7984735 TI - The 1989-90 migration of Kashmiri Pandits: focus on children. AB - Analysis of personal interviews from a sample of 42 Kashmiri Pandit families living in large community halls indicated the migration affected the intra- and interfamily interactions. In trying to keep their ethnic identity, they also had to adapt to their new environment. For the Kashmiri Pandits the sense of being uprooted was felt very strongly as there was a complete change in ecology and loss of status, property, and prestige. The community had taken over the role of socialization. The younger children (4-11 years) expressed enjoyment of communal living more than the older group (12-18 years). Children reported being closer to their mothers. Incidence of child abuse was reported as higher since migration. Girls disliked camp living more than boys. Most of the children were performing above average at school. Children preferred to speak in their native language at home. PMID- 7984736 TI - Efficacy of lithium chloride in the taste-aversion conditioning of young-adult and old-age rats. AB - An absolute amount of a LiCl US was administered to 24 young-adult and 24 old-age rats during taste-aversion conditioning to determine whether the superior performance of old-age rats, when a 1% body-weight injection of a LiCl US is administered 3 hr. after a saccharin CS, is due to age-related differences in US intensity or the efficacy of LiCl. The aversion conditioned in old-age rats with a 3-hr. CS-US interval and an absolute amount of LiCl was still significantly greater than that in young adults suggesting that age-related differences in US intensity or the efficacy of LiCl cannot explain the superior performance of old age rats. Possibly, old-age rats forget the specifics of the CS more than young adults and, thus, older animals show greater stimulus generalization to the substantially different test stimuli. PMID- 7984737 TI - Causal attributions for marital violence and emotional response by women seeking refuge. AB - The aim was to examine the association between causal attributions for marital violence and emotional reactions of 15 women from two refuges in Northern Ireland. The women who perceived the cause of the violence as stable and uncontrollable scored higher on the Avoidance and Intrusion subscales of the Impact of Events Scale, respectively. In addition, more global causal attributions were associated with higher scores on Intrusion and Avoidance as well as depressive symptomatology as measured by the Beck Depression Inventory. No evidence was, however, found to support the view that these women were engaged in self-blaming (attributions tended to be overwhelmingly external). PMID- 7984738 TI - Management of anger and its effect on incarcerated assaultive and nonassaultive offenders. AB - Scores of inmates who had been incarcerated for assaultive offenses, property offenses, or a combination of offenses were compared on personality and intelligence inventories. Anger-management programming was given to 57 male offenders two hours per week over five weeks. Self-esteem, anxiety, and aggression, measured before and after the program, showed significant differences. PMID- 7984739 TI - Smokeless tobacco consumption by Mexican-American University students. AB - A modified version of the Illinois Department of Public Health Smokeless Tobacco Survey was administered to 220 women and 134 men attending a state university in New Mexico. The respondents included 65 male and 83 female Mexican-Americans as well as 118 female and 59 male Anglo-Americans. All Mexican-American women identified themselves as nonusers of smokeless tobacco. Of the Anglo-American women, one indicated that she used snuff, and 3 disclosed that they chewed tobacco. 33% of the Anglo-American men and 18% of the Mexican-American men stated that they used smokeless tobacco products. A chi-squared analysis showed this difference was significant. Implications are discussed. PMID- 7984740 TI - Stress reduction in child-abusing families: global and specific measures. AB - This study compared in-home treatment to traditional county services for their ability to reduce stress in child-abusing families. 47 families who were at risk for having at least one child removed from the home for child abuse were referred to Families First for an intensive 6-wk., in-home therapy program. A comparison group of 29 families who were also at risk for having at least one child removed for abuse received traditional county services but no in-home therapy. Stress scores used were derived from a factor analysis of the Family Inventory of Life Events and Changes (FILE) that had identified 10 stress factors. The stress data were analyzed by a series of 2 x 2 analyses of variance, group and time being the independent variables and the stress factors the dependent variables. Total stress was significantly reduced over time for both groups, and several specific stress factors were also significantly reduced over time. In secondary analyses, 2 x 3 (group by time) analyses identified interactions for total stress and three of the individual stress factors. In-home treatment was effective in reducing stress, but traditional services were also effective. Some possible explanations were discussed. A major finding was that, by including analyses using the specific stress factors (rather than just the Total Stress score), a much richer understanding of the role stress plays in abusive families is provided. It was concluded that, although global stress may be reduced by different methods, some specific types of stress are more likely to be reduced than others. PMID- 7984741 TI - Neuroticism and negative affect measures as predictors of psychological distress. AB - In a year-long study, 106 students (78 women and 28 men, mean age 29 yr.) completed both a self-report Neuroticism and Extroversion inventory and a self report positive and negative affect checklist at the beginning of an academic year. At the end of the academic year, prior to final examinations, they completed a self-rating scale for depression. The Neuroticism score was the only significant independent predictor of students' end-of-year levels of psychological distress. PMID- 7984742 TI - Early childhood special educators' perceptions of school psychologists' roles in their programs. AB - Perceived and preferred roles of 67 school psychologists in early childhood special-education programs were examined in a partial replication with 268 respondents in Illinois of Mowder, Willis, and Widerstrom's work. The most commonly cited reason for consultation with school psychologists was related to psychological assessment, with information on children's functioning as the most likely benefit. Respondents preferred the mental health model. Although respondents were satisfied with the roles of school psychologists, they presented several concerns about expanded roles for school psychologists. PMID- 7984743 TI - Adult attachment, love styles, and self-defeating personality characteristics. AB - The present research showed for 79 men and 79 women that people with more characteristics of the proposed self-defeating personality diagnosis had less secure adult attachments. In addition, self-defeating women described their style of loving as game playing and being less romantically involved. Both men and women who were more self-defeating, once in a relationship, reported feeling dependent, jealous, and desperate to maintain it. These results are consistent with the 1993 findings of Williams and Schill that people with more self defeating characteristics were more likely to lack secure attachments with parents. PMID- 7984744 TI - On form level on the Rorschach. AB - Research has established the clinical value of form level assessment. An issue remaining to be addressed involves the scoring of form level. Currently, several systems of scoring form level are in use, e.g., Rorschach's (and, hence, Beck's, Hertz's, and Piotrowski's) 2-category scale (F+, F-), Klopfer's 3-category scale (F+, F, F-), Exner's 4-category scale (F+, Fo, Fu, F-), and Rapaport's 7-category scale (F++, F+, Fo, F +/-, F -/+, Fv, F-). Further, Rorschach scored form level only for responses scored: F; Klopfer, on the other hand, scored form level for any response on which form was dominant, e.g., M+, FC+, F shading +). The question can be raised as to how refined a scaling of form level is needed to yield the most useful information and whether deriving a percentage form level for each determinant yields any more information than an assessment based only on responses scored F or an over-all R + %. The question was raised whether assessing the quality of organizational activity and detailing might contribute more information about personality than the current system of scoring form level in terms of goodness of fit between percept and blot. These questions need to be answered by research. PMID- 7984745 TI - Validation of the Impact of Event Scale on a sample of American Vietnam veterans. AB - The goal of the present report is to validate the Impact of Event Scale for use as a measure of the enduring nature of reactions to combat stress by 60 American Vietnam veterans. Validity was supported through significant correlations with measures of abusive violence and combat exposure. From factor analysis a single factor (general level of distress) supported the validity of the scale and thereby further use with Vietnam veterans. PMID- 7984746 TI - Quality of life in adult recipients of bone marrow transplantation. AB - Quality of life, coping styles, and satisfaction with health care were assessed in 32 bone marrow transplant recipients and 22 conventional chemotherapy recipients. Subjects reported having generally good quality of life with no significant differences in quality of life or coping styles between the two groups. Quality of life was not significantly associated with age, socioeconomic status, time since diagnosis, or time since last treatment, although lower scores were associated with a passive coping style. Interestingly, bone marrow transplant recipients reported greater over-all satisfaction with health care and more contentment with the cost and convenience of health-care delivery than did conventional chemotherapy recipients. PMID- 7984747 TI - Assessment of anxiety in adolescents: concurrent and factorial validities of the Trait Anxiety scale of Spielberger's State-Trait Anxiety Inventory for Children. AB - The purpose of this study was to evaluate the concurrent and factorial validities of the Trait Anxiety scale of Spielberger's State-Trait Anxiety Inventory for Children when given to 157 adolescents. Using a randomly selected subsample of 88, correlations between total and factor scores on the children's inventory and on the Revised Children's Manifest Anxiety Scale were statistically significant but lower than those reported previously for children. Principal component analyses of these adolescents' scores on the Trait Anxiety scale of the children's inventory replicated previous factor analytic studies of this inventory administered to children. Total scores for these adolescents on the children's and adults' Form Y inventories were only moderately correlated. rs between the two sets of factor scores were low. These findings raise the question of whether the Trait Anxiety scale of the children's inventory when completed by adolescents measures the same construct of trait anxiety as the adult inventory. Researchers must evaluate further the validity of the children's inventory Trait Anxiety scale when administered to adolescents. PMID- 7984748 TI - Self-reports of sexual abuse, mental health status, and perceived confusion of family roles: a retrospective study of college students. AB - This study examined the possibility that mental health problems which may result from sexual abuse are exacerbated by a confusion of family roles in the victim's perception of the family of origin. A sample of 234 undergraduate students completed a questionnaire. Analyses confirmed associations between (1) perceived sexual abuse and indicators of mental health problems, (2) confusion of family roles and perceived sexual abuse, and (3) mental health problems and confusion of family roles. A good prediction of the occurrence of mental health problems could only be obtained if both perceived sexual abuse and the confusion of family roles were considered. PMID- 7984749 TI - Economic and social correlates of suicide in Caribbean nations. AB - Using data from the 1970s, it was observed that the gross national product per capita was positively associated with male suicide rates in the Caribbean islands, with sociological variables playing a smaller role. In contrast, sociological variables played the more important role in the associations with female suicide rates. PMID- 7984750 TI - Religious attitudes and obsessional personality traits among UK adults. AB - Recent data of Maltby, McCollam, and Millar were reanalysed to examine the relationship between religious attitudes and obsessional personality traits in a sample of UK adults. For 34 men and 85 women significant correlations were found between the Francis Scale of Attitudes Towards Christianity and the Sandler Hazari Obsessionality Inventory trait scale. This supports previous findings linking religious attitudes and obsessional personality traits in student samples. PMID- 7984751 TI - Making love: Australian adults' rating of its importance as a romantic act in a relationship. AB - A personal opinion survey was administered to 1207 adults assessing attitudes towards 13 romantic acts with regard to age and gender. The present study focused upon attitudes towards the perceived importance of making love as a romantic act in a relationship. The sample was divided into three age groups, 18 to 25 years, 26 to 35 years, and 36 to 45 years. Analysis showed that 600 men's mean rating on a 5-point scale for importance was higher than the 607 women's rating; however, no significant difference was found among age groups and the interaction of age and gender was nonsignificant. PMID- 7984752 TI - Bulimia: an empirical analysis of psychodynamic theory. AB - This study examined two aspects of psychodynamic theory concerning bulimia nervosa, that bulimic patients ascribe to a traditionally feminine sex-role and that bulimic women have difficulty differentiating emotional from visceral sensations. 18 bulimic and 18 control women were administered the Bem Sex-role Inventory and the Eating Disorder Inventory. Contrary to dynamic theory, bulimic women were not more likely classified as traditionally feminine than control subjects; however, significantly more controls than bulimic women were classified as androgynous. Analysis of scores on the Eating Disorder Inventory's Interoceptive Awareness scale indicated a significant difference between bulimic persons and controls, providing strong support for the hypothesis that bulimic women have a difficult time differentiating emotional from visceral sensations. PMID- 7984753 TI - Drug law enforcement expenditures and drug-induced deaths. AB - The association between federal expenditures for drug law enforcement and the number of drug-induced deaths in the USA from 1981 through 1991 was examined. Significant positive associations were found for both numbers of deaths and death rates. PMID- 7984754 TI - Case study of a conduct-disordered youngster: building ego defenses and improving object relations within a therapeutic alliance. AB - The classification of Conduct Disorder, sometimes seen as a nonspecific designation descriptive of antisocial behavior, is illuminated through case study of a youngster admitted for acute hospital treatment. Drawing on psychodynamic theory and treatment, principles are used in illustrating how individual, historical, family, and trauma factors may contribute to disordered self-esteem and behavior, which may become a focus of therapeutic intervention. A concluding section delineates the possibility of two varieties of Conduct Disorder related, respectively, to trauma or failures in socialization. These may have implications for treatment and setting. PMID- 7984755 TI - Effects of gun control on homicide in Canada. PMID- 7984756 TI - Estimation of parental IQ. AB - 217 undergraduates, their parents, and grandparents were asked to estimate the IQs of themselves as well as those of their parents. Previous research has shown the existence of a gender-related bias that affects the ability of younger adults to estimate the IQs of their parents. The results of this survey showed that, in contrast to young and middle-aged individuals, older adults estimated the IQs of their parents to be equal to their own. PMID- 7984757 TI - Psychometric properties of the Brazilian Health Locus of Control Scale. AB - Based on social learning theory, the construct of health locus of control has proven valuable in predicting a wide variety of health-related behaviors. In studying this concept among Brazilians, the psychometric properties of the Multidimensional Health Locus of Control Scale translated into Brazilian Portuguese were investigated in a sample of 280 middle-class persons. Three types of health locus of control were verified, internal, powerful others, and chance. Further refinement of subscales is needed to improve internal consistency reliabilities. PMID- 7984758 TI - Factitious disease. PMID- 7984759 TI - Patients suffering from factitious disorders in the clinico-psychosomatic consultation liaison service: psychodynamic processes, psychotherapeutic initial care and clinicointerdisciplinary cooperation. PMID- 7984760 TI - The biography of the factitious-disorder patient. PMID- 7984761 TI - Countertransference in factitious disorder. AB - In the treatment of patients with factitious disorder it is important to realize that at various levels of their experience these patients are more intimate with death than with life. This requires a particular awareness of resistance mechanisms to countertransference as well as of the importance of clinical procedures, in particular with regard to superego analysis. A requirement for establishing a psychotherapeutic alliance with patients suffering from factitious disorder is a high degree of 'therapeutic eros', hope and trust in one's own capabilities. The emphasis on a 'biophile attitude' does, however, involve the danger that the destructive potential, fantasies of death or killing, but above all feelings of guilt and shame are euphemistically interpreted and played down. A supportive superego analysis is viewed by the patient as playing down her or his 'terror of conscience' and a sense of being left alone. The therapist can be of greater help to the patient by focusing on his or her need and by escorting him or her. This requires that the therapist accept the feelings of relentlessness and hopelessness experienced by the patients in her- or himself. By relinquishing the denial of death-directed tendencies, the therapist is able to establish normality, reality and structure, and is thus in a position to exert a stabilizing effect, initially on her- or himself, but frequently also on the patient, for whom new horizons open. PMID- 7984763 TI - Diagnosis and classification of factitious disorder with operational diagnostic systems. PMID- 7984762 TI - Excerpt from the treatment of a patient with otitis externa artefacta. PMID- 7984764 TI - An internist's view of patients with factitious disorders and factitious clinical symptomatology. PMID- 7984765 TI - Factitious disorders in the field of surgery. PMID- 7984766 TI - Factitious disease in the field of dermatology. PMID- 7984767 TI - Factitious disorders in the field of neurology and psychiatry. PMID- 7984768 TI - Syndromes related to factitious diseases. PMID- 7984770 TI - Munchhausen syndromes and factitious diseases. PMID- 7984769 TI - Diagnosis of narcissistic self-esteem regulation in patients with factitious illness (Munchausen syndrome). AB - A quantitative taxonomy for the identification of patients with narcissistic pathology and with borderline personality disorders based on test results is presented. The quantitative identification of these subgroups was produced using a Q-factor analysis. Based on the correlation of the subjects by means of the 241 questions from the narcissistic inventory of Deneke and Muller [27], three subgroups could be defined. Two of these groups exhibited a pathology of the self system which corresponded to the pathology described by Kernberg [24] for narcissistic and borderline personality disorders. The third group is characterized by reduced observable self-pathology traits from the narcissistic inventory. By means of the reclassification of these three taxonomical groups with the discriminant analysis, two discriminant functions could be calculated, using the weighting of the single test scales for a classification of new patients. These classification functions were used to examine 18 patients suffering from factitious disorders. The evaluation of test profiles with the reduced narcissistic inventory of Deneke and Muller [11] in order to identify the three taxonomical groups showed that 9 patients (50%) had a borderline personality disorder and 6 patients (33%) a narcissistic personality disorder, while 3 patients (17%) could be assigned to the subgroup without self-pathology. In summary, 83% of the examined patients with factitious disorders exhibited a disorder in self-regulation. The previous clinical observations of self regulation for patients with factitious disorders could thus be confirmed. It becomes clear that different high levels of disorder in self-regulation (position in the sphere of the discriminant function) correspond to varying degrees of prognostic significance. PMID- 7984771 TI - The body as a transitional object. PMID- 7984772 TI - Overt self-injury. PMID- 7984773 TI - Structural disturbances in the body self. PMID- 7984774 TI - Inpatient and outpatient long-term psychotherapy of patients suffering from factitious disorders. AB - A favorable therapeutic course is achieved by the combination of an initial clinical psychotherapy and a subsequent analytical long-term treatment implemented as an outpatient therapy or an interval therapy. This form of therapy was offered to all of the patients and was accepted by half of the patient collective, i.e., by 12 out of 24. Only in 1 of these 12 cases, was it possible to dispense with the initial clinical therapy in favor of a primary outpatient therapy. Of these 12 therapies, 2 were terminated by the patients. We were able to continue the other 10 for longer periods, extending up to 4 years. In this setting, a transition from the working phase to the separation phase is possible around the fourth year of therapy. Termination of therapy is almost always based on a negative therapeutic reaction. The patients were generally capable of development, but were not able to take advantage of this opportunity because of the dominance of malignant introjects. In several cases, this pattern has become consolidated on a social as well as an endopsychic level. The therapy is then terminated in favor of a structured mother-child relationship or a similarly structured marriage. In those cases where the therapy was broken off prematurely, the establishment of a sufficiently stable working relationship was prevented by the predominantly negative transference. As a result, it was not possible to conduct a follow-up therapy after the normal end of the clinical psychotherapy, for example. The question remains whether a significant lengthening of the clinical psychotherapy could have changed anything here; in my opinion, this is not the case. In these cases, the inpatient therapy was always terminated by the patients, either by a directly expressed wish or by a symptomatic development making referral or discharge imperative. The 10 cases undergoing long-term therapy all progressed favorably, with a significant, or at least marked, improvement of the symptomatology and the relationship capability. In this context, the results are, in each case, a function of the severity of the illness, the individual capability for growth, and the length of treatment. Even though 6 of the 10 long-term therapies are now in the separation phase, none of them has been finally ended yet. As a result, we have only a small amount of information so far on the possibilities for reaching a final conclusion of the therapy.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 7984775 TI - Structure of viral connectors and their function in bacteriophage assembly and DNA packaging. PMID- 7984776 TI - Specificity and promiscuity in membrane helix interactions. PMID- 7984777 TI - Epidemiology of osteoporosis. AB - Prevention is particularly important in osteoporosis since the loss of bone strength that accompanies bone loss is not known to be reversible. Identification of those at risk by measurement of risk factors may help target prevention efforts. Low bone mass and a propensity for falling are established risk factors for osteoporotic fracture in the elderly; some other risk factors for fracture may operate through these two pathways. There has been little epidemiologic study of other potential causes of fracture such as poor bone quality and trauma biomechanics, and little is known about risk factors that may operate through these pathways. PMID- 7984778 TI - Osteoporosis in patients with rheumatic diseases. AB - Arthritis and other musculoskeletal disorders are common causes of disability in the United States. Osteoporosis is the major nonarthritic musculoskeletal condition affecting postmenopausal women. An increased incidence of osteoporosis is seen in some rheumatic diseases resulting in a potential increase in risk of fracture. Patients with rheumatoid arthritis and spondyloarthropathies appear to have decreased bone mineral density whereas patients with osteoarthritis of the hip have increased bone mineral density. In this article studies of bone mass and related fractures in patients with rheumatic disorders are reviewed. PMID- 7984779 TI - Peptides and growth regulatory factors in bone. AB - All bone is remolded by bone resorbing (osteoclasts) and bone forming (osteoblasts) cells that are under the regulatory control of local factors generated in the bone cell microenvironment. These local factors are comprised of peptides and nonpeptides, including arachidonic acid metabolites such as prostaglandins of the E series and the leukotrines. Most is known of the peptides the stimulate or inhibit osteoclastic bone resorption, but information is also now accumulating on the peptide growth factors that are incorporated into the bone matrix, released in an active form when bone is resorbed, and stimulate those cellular events that result in bone formation. In this article these control mechanisms are reviewed. PMID- 7984780 TI - Biochemical markers of bone turnover for the clinical assessment of bone metabolism. AB - Despite these potential problems, biochemical bone markers are the single most sensitive method for monitoring acute changes in bone metabolism. For example, subcutaneous injections of recombinant human insulin-like growth factor I cause a measurable increase in both procollagen and urinary DPD in as little as 1 day. Similarly, it is possible to measure a significant decrease in bone formation as determined by decreases in serum levels of ALP, OC, and C-PCP within 12 hours after the beginning of a PTH infusion study. Additionally, an increase in DPD/cr was determined within 24 hours of the start of bed rest. These changes, seen within 24 hours, are far earlier than could be detected by any other method of monitoring bone metabolism. Thus, biochemical assays have opened a new era where changes in bone metabolism can be detected in hours to days. This acute detectability should be especially helpful to the development of new drugs and the optimization of the use of approved drugs. Accordingly, definite dose response studies can now be done in a reasonable time. For osteoporosis therapy there are reasons to consider cyclic drug administration, such as avoiding drug resistance (PTH or calcitonin), avoiding overtreatment (bisphosphonates), or avoiding a possible mineralization defect (fluoride). By using biochemical assays, we can determine the optimum amount of "on time" and "off time" in cyclic therapy. Of the bone formation assays, ALP, OC, and PCP, we recommend for routine use the OC assay because of its high discriminant power and because it has been better characterized, in terms of clinical application, than the PCP assays and the ALP IRMA. If, however, the serum cannot be drawn at a specific time in all patients to be studied, we recommend the ALP assay because, unlike the OC assay, it shows no diurnal variation. Of the bone resorption assays, HYP, TRAP, GHYL, and PYD/DPD, we recommend the urine PYD/DPD assay (adjusted for creatinine) because it is commercially available and because, along with the urine GHYL assay, it is the most sensitive bone resorption assay. Established guidelines for the use of assays in patient care is not yet available, largely because of the large intrapatient variation seen with most assays. Once this problem is resolved, it should be possible to apply biochemical assays to routine clinical practice. For example, if the patient has a urine DPD/cr (indicating a high bone resorption rate), the patient would be selected for antiresorptive therapy, and subsequently the urine DPD/cr assay would be repeated during therapy to determine the effective dose of the drug.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 7984781 TI - Bone biopsy and histomorphometry in clinical practice. AB - Transilial bone biopsy after tetracycline labeling coupled with histomorphometry has become an indispensable tool in the clinical research of metabolic bone disease, especially in evaluating the long-term safety and efficacy of therapeutic agents proposed for treatment of bone disease. It is probably not necessary for the majority of patients who seek medical care for bone diseases such as osteoporosis. It is particularly useful in the management of patients with end-stage renal disease who develop symptomatic bone disease because it may be the only means of deciding on proper treatment. The biopsy can be performed safely by nearly any clinician after brief training. Tetracycline labeling must be accomplished before the biopsy, and the specimen must be handled carefully to avoid removal of the mineral or disturbing the label. Embedding, sectioning, staining, and analysis must be performed without removal of the mineral. The difficulty of this methodology has limited its availability. Nevertheless, it can be applied in most situations in which there is clear benefit to patient management. PMID- 7984782 TI - Glucocorticoid-induced osteoporosis. AB - Glucocorticoids are important in the management of rheumatic diseases. Bone loss is one of the most devastating side effects of glucocorticoids because they inhibit calcium transport, cause secondary hyperparathyroidism, hypogonadism, and impairment of osteoblast function. Efforts to control these side effects minimize bone loss. PMID- 7984783 TI - Noninvasive bone mineral density measurement in the evaluation of osteoporosis. AB - Bone densitometry has developed considerably during the past several decades. Because the techniques have become more precise than before, osteoporotic patients can now be followed over time, allowing for assessment of disease or response to treatment. Several densitometry techniques have been shown to allow for the assessment of fracture risk. Factors other than density, however, additionally influence fracture risk. The next step will be the evaluation of microstructure and bone quality. PMID- 7984784 TI - Heterogeneity in osteoporosis. Men versus women. AB - Although osteoporotic fractures have long been considered a special problem for postmenopausal women, osteoporosis is also an important clinical issue in men. The causes and clinical spectrum of osteoporosis is similar in men and women, but there are definite gender differences that reflect sexual differences in skeletal development, age-related bone loss, and secondary causes of metabolic bone disease. PMID- 7984786 TI - Treatment of osteoporosis with bisphosphonates. AB - Several bisphosphonates appear to be effective for preventing bone loss associated with estrogen deficiency, glucocorticoid treatment, and immobilization and for partially reversing bone loss in patients with postmenopausal osteoporosis and steroid-induced osteoporosis. The most promising of these agents are etidronate, alendronate, tiludronate, and risedronate. These agents should have an important role in prevention and treatment of osteoporosis; however, more research is needed regarding optimal doses and regimens (continuous versus intermittent), comparisons with other agents, and use in combination with other agents. PMID- 7984785 TI - Calcium, estrogen, and progestin in the treatment of osteoporosis. AB - An adequate calcium intake is important to attain peak bone mass and to oppose that component of age-related bone loss due to insufficient intestinal calcium absorption. Calcium and appropriate vitamin D supplements are particularly important for preventing cortical bone loss and associated hip fractures in the elderly (Type II osteoporosis). Within the initial 5 years following menopause, there is an accelerated loss of trabecular bone from the spine and distal radius (Type I osteoporosis). At that time, estrogen replacement is most effective for preventing the rapid trabecular bone loss that could otherwise result in vertebral or Colles' fractures. During this early period of estrogen deficiency when excessive bone turnover is releasing large amounts of calcium into the circulation, supplemental calcium is ineffective. Progesterone, often given with estrogen to prevent endometrial carcinoma, may itself have a trophic influence on bone. PMID- 7984787 TI - Current and investigational approaches for reversing established osteoporosis. AB - Osteoporosis is a disease of elderly women marked by low bone mass and increased risk of fracture. Though its prevalence can be reduced by timely estrogen replacement at menopause, many persons present with fragility fractures long after much bone has been lost. Osteoporotic subjects have low bone mass and poor structure but few or no metabolic abnormalities, such as ongoing bone loss, for treatment to normalize. The problem is to increase their bone mass and improve their bone structure. Today's major therapeutic approaches are summarized in Table 2. Ironically, they aim at stopping bone loss. Although preventing the skeleton of an osteoporotic person from growing weaker by stopping bone loss is better than allowing the process to continue, raising her to a significantly higher level of bone mass would be a better aim. Existing agents that stop bone loss by reducing turnover also increase bone mass mildly by filling the remodeling space. The result is a rise in bone mass during the first year or two of treatment to a new steady state 2% to 5% higher than baseline that persists throughout treatment. Fluoride increases spinal bone mass markedly. It decreases vertebral, but not hip fractures, but is associated with side effects and a nonresponse rate that makes pursuing other therapies attractive. Agents that upregulate bone mass through regulatory means have been tested in preclinical and a few clinical trials. PGE2 has been thoroughly tested preclinically. By studying PGE2, the field has learned that marked bone mass increases in the estrogen deplete osteopenic skeleton are possible. The lack of bone specificity for PGE2 will probably limit its use to that of preclinical demonstration agent but leave open the possibility that less potent members of the prostaglandin family with better bone specificity might have promise as osteoporosis treatments. PTH or one of its analogues shows good promise for osteoporosis treatment. The wide availability of cheap PTH or proprietary analogues with similar activity will do much to speed its development. It increases bone formation and cancellous bone mass markedly. If PTH increases bone mass consistently in either large animal or human trials while causing only mild transient cortical bone mass declines, it can be a successful osteoporosis treatment agent. Bone growth factors appear to have much untapped potential for furthering the understanding of local control of bone processes and possibly for treating osteoporosis. Another possibility is biphasic therapy.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 7984788 TI - Role of vitamin D, its metabolites, and analogs in the management of osteoporosis. AB - Vitamin D and its metabolites are well-established regulators of bone mineral homeostasis. Their clearest role is in the prevention and treatment of rickets and osteomalacia, bone diseases characterized by inadequate bone formation, and mineralization. Much of the effectiveness of vitamin D and its active metabolite 1,25(OH)2D in treating such disorders rests with their ability to increase serum levels of calcium and phosphate principally by stimulating intestinal calcium and phosphate absorption. Osteoporosis is not a disease resulting from obvious deficiencies in vitamin D, calcium, and phosphate. More subtle deficiencies, however, may be found, especially among the elderly with decreased intake of dairy products, reduced sunlight exposure, and less efficient intestinal absorption of bone minerals. Such subtle deficiencies may account for the ability of vitamin D and calcium supplementation to have a beneficial effect on bone mineral density in this population. Estrogen administration to postmenopausal females raises 1,25(OH)2D levels, presumably through increased renal production, and this increase is associated with increased intestinal calcium transport. Serum measurements of the vitamin D metabolites in general, however, and 1,25(OH)2D in particular do not consistently show evidence of a decrease at the time of menopause. Although most studies show a fall in intestinal calcium transport with age, which can be reversed with 1,25(OH)2D or estrogen, even these observations have not been found consistently. Thus, some investigators have addressed the issue of tissue resistance to 1,25(OH)2D and have noted decreased VDR in the intestine and reduced 1,25(OH)2D accumulation by bone with age. Despite no obvious deficiency of vitamin D in most patients with osteoporosis, clinical trials with vitamin D or 1,25(OH)2D show promise. Vitamin D treatment will probably prove most efficacious in populations with marginal vitamin D intake and/or limited sunlight exposure; high doses would not be required, and the treatment would be safe. This would be a physiologic and not a pharmacologic use of vitamin D. The use of 1,25(OH)2D for treatment of osteoporosis in individuals with adequate nutrition and sunlight exposure may require somewhat higher than physiologic doses to be effective. Perhaps such doses are necessary to stimulate osteoblast activity and/or differentiation; by raising the serum calcium level, such doses of 1,25(OH)2D might block its otherwise stimulatory effect on osteoclast number and activity. Such doses run the risk of hypercalcemia and hypercalciuria, leading to nephrolithiasis and/or nephrocalcinosis. These undesirable side effects appear to be less common with the use of 1 alpha OHD compared with 1,25(OH)2D, but this may be because of the lower levels of calcium consumption in Japan where 1 alpha OHD is widely prescribed.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 7984789 TI - Calcitonin therapy in osteoporotic syndromes. AB - Since its introduction in 1961, calcitonin has effectively been used to reverse bone loss observed in paraplegic patients, atrophy of bone, and other disorders. This article focuses on the effect of calcitonin therapy in the treatment of osteoporosis. PMID- 7984790 TI - Overview of exercise and bone mass. PMID- 7984791 TI - [Binswanger's disease]. PMID- 7984792 TI - [Binswanger's disease and its relationship with vascular risk factors]. AB - INTRODUCTION: Lesions in the periventricular white matter are a quite common neuroradiological finding in older patients. They are called leukoaraiosis and can be associated to several syndromes. OBJECTIVE: To study the relation between leukoaraiosis and the different vascular risk factors that can be involved in its development. METHOD: Fifty consecutive patients with leukoaraiosis in CT scan were included as well as fifty age and sex-matched controls; all of them belonged to the same population. Previously vascular risk factors were defined according to strict criteria. RESULTS: The commonest vascular risk factor was arterial hypertension, in second place previous cerebrovascular accidents and in third place heart diseases. There was a very significant difference for hypertension in the univariant analysis, which was subsequently confirmed in the multivariant analysis. CONCLUSIONS: The vascular risk factor most strongly associated to leukoaraiosis was arterial hypertension followed by cerebrovascular disease and heart diseases. The remaining of the analysed factors had a insignificant prediction power. PMID- 7984794 TI - [The burn-out syndrome in physicians of the public health system of a health area]. AB - The syndrome of professional exhaustion (burn-out) and the influence of work conditions are studied among 273 physicians of the Public Health System, 143 specialists and 130 Primary Care physicians. All of them answered two questionnaires: the Maslach Burn-out Inventory and another questionnaire related to the job. The results show significantly higher levels of exhaustion in the specialists than their fellow-workers in Primary Care units. Both groups are also compared to the original American sample. The results are commented in the context of a possible influence of a Health Reform. The urgent necessity of managerial measures to stop and prevent the Syndrome is concluded. PMID- 7984793 TI - [Reactive arthritis. Prospective clinico-microbiologic study]. AB - We study with a prospective design all reactive arthritis diagnosed at the Service of Rheumatology in Bellvitge Hospital during a thirty months period, from August 1985 to February 1988; in order to describe its clinical features, etiological factors and prognosis. Thirty patients who fulfilled the admission criteria were admitted to the study. A previously designed protocol of clinical, serological and microbiologic study was applied to all. A microorganism was identified in 21 patients. In 14 cases it was Yersinia enterocolitica, in 4 Chlamydia trachomatis, in 2 Salmonella enteritidis and in 1 a group A beta hemolytic Streptococcus. The averaged length of the disease was 7.6 +/- 8 months. PMID- 7984795 TI - [Follow-up of antitubercular treatment]. AB - Tuberculosis is a first magnitude sanitary problem with several factors that make difficult its eradication, among these are particularly important those derived from the antituberculous therapy: noncompliance and adverse reactions to the drugs used. We have developed a follow-up program for ambulatory patients with antituberculous therapy that includes compliance control and systematical survey or possible adverse reactions. We expose our results after its application to 39 patients with tuberculosis and 24 with tuberculous infection. The compliance level among patients with tuberculous disease was 100% and among those who were receiving chemoprophylaxis 75%, both values much higher than those found in the literature. We detected adverse reactions in 43.6% of the patients with tuberculous treatment and 37.5% of those receiving chemoprophylaxis with isoniazid. Setting up follow-up programs in antituberculous treatments notably helps to improve the compliance and the safety of treatment. PMID- 7984796 TI - [Clinical and serologic course of patients with mixed connective tissue disease]. AB - The so called mixed connective tissue disease (MCTD), continues to be a controversial entity, while some authors considered it a good characterized disease, others think that is an undifferentiated connective tissue disease. OBJECTIVE. To analyse the clinical and serological evolution of a group of patients diagnosed of MCTD, with particular consideration to the meaning of anti nRNP and anti-Sm antibodies. METHOD. We have studied 20 patients diagnosed of MCTD and 112 with systemic lupus erythematosus (SLE). Anti-nRNP and anti-Sm antibodies were detected through counter immunoelectrophoresis, immunoblotting and ELISA. RESULTS. After an average time of evolution of 10 years, 70% (14/20) of the patients diagnosed of MCTD fulfill criteria for SLE (6 cases), scleroderma (6 cases) or polymyositis (2 cases). Anti-nRNP response is persistent, directed mainly against the 70 Kd and A-nRNP polypeptides and qualitatively higher in MCTD in SLE (absorbencies 2.64 vs 1.25. The immunoblotting test detected anti-Sm antibodies in 5 patients (25%) and ELISA test in 14 (70%). CONCLUSIONS. Clinical and serological evolution suggest that MCTD is an undifferentiated connective tissue disease. Anti-nRNP antibodies are characteristic, although anti-Sm antibodies can be detected with ELISA regardless whether on not patients fulfill SLE criteria. PMID- 7984797 TI - [Cryptococcosis with exclusive cutaneous presentation in a patient with AIDS]. AB - We report an exclusively cutaneous case of cryptococcosis, which is exceptional. He was a 33 years old patient with the acquired immunodeficiency syndrome who presented with an ulcer-necrotic lesion at the nasal wings with a long and torpid evolution. Finally, culture and biopsy were diagnostic of cryptococcosis. We ruled out affection of other organs and the cryptococcal antigen was negative in serum and cerebrospinal fluid. The patient was treated with fluconazole and had a good clinical course. Its emphasized the scarcity of this form of presentation as well as the lack of specificity of its lesions and the necessity of ruling out other locations once the fungus is isolated in the skin. Diagnosis is simple through skin biopsy and culture. Its important to determine the cryptococcal antigen. We comment on the current approaches to treatment during acute and maintenance phases, after the appearance of the new imidazolic compounds such as fluconazole. PMID- 7984798 TI - [Nutritional status assessment]. PMID- 7984799 TI - [Energetic, proteinic, mineral, and micronutrient requirements]. PMID- 7984801 TI - [Diagnostic strategy in suspected myasthenia gravis]. PMID- 7984800 TI - [Consequences of malnutrition in the patient]. PMID- 7984802 TI - [Young male with lytic lesion of the calcaneus]. PMID- 7984804 TI - [A 34-year-old woman with back pain and lytic lesions of the vertebrae]. PMID- 7984803 TI - [Renal carcinoma and changes in liver biochemistry]. PMID- 7984805 TI - [Cardiac amyloidosis and light chain myeloma]. PMID- 7984806 TI - [Impact of hospital oxygen therapy on the extrahospital field]. PMID- 7984807 TI - [Asthmatic crisis caused by inhaled heroin]. PMID- 7984808 TI - [Papillary carcinoma of the thyroid and Hurthle++-cell adenoma associated with Graves' disease]. PMID- 7984809 TI - [Diffuse mediastinal lipomatosis and exogenous obesity]. PMID- 7984810 TI - [Treatment of thrombophlebitis with nitroglycerin]. PMID- 7984811 TI - El fenomeno suicida en cepas de Aeromonas mesofilas aisladas de muestras clinicas [The suicide phenomenon in strains of mesophilic Aeromonas isolated from clinical specimens]. AB - A study was carried out to determine the occurrence of the suicide phenomenon in Aeromonas spp strains, isolated from clinical samples, and to establish its relationship with the clinical manifestations of diarrheal diseases. 23 strains were studied: 10, of Aeromonas sobria; 7, of Aeromonas hydrophila; and 6, of Aeromonas caviae. All suicidal strains were isolated from patients with acute diarrheal disease. 3 out of 8, isolated from non-diarrheic feces, showed an intermediate phenotypic profile. Various growth patterns associated to the suicide phenomenon were reported. PMID- 7984812 TI - [The use of ELISA and indirect immunofluorescence technics for the rapid detection of eastern equine encephalomyelitis]. AB - We present the results attained in the identification of Eastern equine encephalomyelitis virus isolations in Vero and XL-2 cell systems, using a double antibody ELISA technique and the indirect immunofluorescence method. The results attained through these two techniques coincided by 100% with identification through neutralization. With the former, the virus was detected within 6-8 hours after inoculation. Better results were attained with XL-2 cells. PMID- 7984813 TI - [The prediction of endemic levels of acute diarrheal diseases in Cuba]. AB - Taking into account the chronological series of weekly report rates of acute diarrheal disease in the 15-64 age group population of each province of the country during the 1986-1989 period, prognosis of the weekly endemic rate and endemic variability limit for the year 1990 were made. Results were compared with the report rates observed during the year. The accurateness of prognosis and the width attained for confidence intervals suggest that report rate values above the saddle point are indicators of a probable outbreak of an acute diarrheal disease epidemic, and thus requiring research. PMID- 7984814 TI - [Laboratory studies of the molluscacidal action of the maguey (Agave legrelliana) on Biomphalaria havanensis]. AB - A study was carried out on the molluscacidal action of agave (Agave legrelliana) on the mollusk Biomphalaria havanensis, host of Schistosoma. Different concentrations of the plant's juice extract were tested to determine lethal doses. 3 experimental series were carried out using 144 mollusks in each. LD50 = 0.14 mL/L and LD90 = 0.47 mL/L were determined using the "probilog" computerized program. The regression equation was Y = 5.29 + 2.53 in X. Density, pH, liquid content and absorbance of the juice were determined. The stability of the A. legrelliana juice extract was compared using LD90 and it was observed that its effectiveness was reduced after long storage periods. The results attained were very encouraging since large volumes of water abounding in intermediate host mollusks can be treated with small quantities of juice at the same time that the toxicity which might be introduced by products of chemical origin is reduced. PMID- 7984815 TI - [A biochemical method for the determination of the altered acetylcholinesterase which confers resistance to organophosphate and carbamate insecticides in Culex quinquefasciatus Say, 1823]. AB - The application of a rapid technique to determine the frequency of the altered acetylcholinesterase gene which confers cross resistance to organophosphate and carbamate insecticides to mosquitoes, was tested. Laboratory strains of Culex quinquefasciatus Say, 1823 were used to apply this technique: A clear differentiation in absorbance values was attained among resistant susceptible homozygous mosquitoes (SS), heterozygous (RS); and homozygous (RR), with residual enzymatic activity values of 10-60; 70-100; and 80-120, respectively. This was clearly differentiated at first sight due to a change of the reaction's yellow color. The gene of the altered acetylcholinesterase was found in the Culex quinquefasciatus strains under study. PMID- 7984816 TI - [The evaluation of the infectious capacity of the parasitic nematode Romanomermis iyengari (Welch, 1964) (Nematoda: Mermithidae) in natural mosquito larval breeding areas]. AB - Field tests were carried out with the nematode parasite Romanomermis iyengari (Welch, 1964) to fight 3 species of mosquito larvae Anopheles albimanus (Wiedeman, 1821); Culex nigripalpus (Theobald, 1901); and Culex quinquefasciatus (Say, 1823) in three ecologically different natural mosquito reservoirs. The release of the nematode embryos (infective stage) in the above-mentioned reservoirs was carried out with a Holder-planta 5 manual sprayer, at 2 atm, and an application dose of 1000 parasite embryos/m2. The parasite embryos were obtained from 6 nematode cultures, soaked in distilled water. Results showed that mosquito larvae were parasitized by R. iyengari as follows: 100% of the A. albimanus and 85% of the C. nigripalpus, in the first reservoir; 85% of the C. nigripalpus, in the second reservoir; and 80% of the C. nigripalpus and 75% of the C. quinquefasciatus in the third one. Thus, the potential use of the nematode parasite Romanomermis iyengari as a biological control agent of mosquito larvae was shown. PMID- 7984817 TI - [Characterization of the influenza epidemic that occurred in 1988 in the Cristobal Labra health area]. AB - A study was carried out on the influenza epidemic which broke out in the 21 804 inhabitant health area of the Cristobal Larra Polyclinic of City of Havana Province on February 29, 1988. It was found that medical consultations for acute respiratory tract infections totalled 2046 during the 30-day epidemic; 1860 of these (90.9%) were first consultations, representing about 9% of the area population. The epidemic peak was reached 22 days after the outbreak. Higher consultation rates were of patients under 5 years, and the highest consultation coefficients were registered on Mondays. The application of the Rvachov-Baroyan model for local epidemic prognosis was not effective in the health area under study. PMID- 7984818 TI - [The identification of Aeromonas species isolated in Cuba]. AB - 100 Aeromonas strains, isolated from children under 5 years with acute diarrheal diseases from various health centers of the country, were studied from January to July, 1990. Using the Janda-modified Popoff's and Veron's model, 63% of the strains were identified in species through primary tests, and 100% of the other 37% were identified in Aeromonas sobria, Aeromonas hydrophila, and Aeromonas caviae, using also supplementary tests. PMID- 7984819 TI - [The infectious etiology of acute diarrheal diseases in the Republic of Cuba, 1991]. AB - This study was carried out in 1991 to learn the behavior of enteropathogenic agents causing acute diarrheal diseases in Cuba. 30 children, admitted in hospitals or seen in outpatient services for acute diarrheal diseases, were selected in each province taking into account that they had not received antibiotic or chemotherapy treatments in the previous 72 hours. Feces samples were taken from all patients for virological, bacteriological, and parasitological studies, and results were sent to the Pedro Kouri Institute of Tropical Medicine. Data were processed in DBASE III. Higher positivity indices were attained in the winter months. The causative agents most frequently found were: rotavirus (8.2%); Entamoeba histolytica (6.1%); and Salmonella (4.2%). Escherichia coli, Campylobacter, Shigella and rotavirus showed higher indices in winter. Shigella flexneri and Shigella sonnei predominated. Salmonella serogroups D, B, and C, and enteropathogenic Escherichia coli 0119 and 026 subsets were the most frequently found. PMID- 7984821 TI - [The presence of mosquitoes (Diptera: Culicidae) and bioregulators in existing breeding grounds in areas served by a family physician in the municipality of Fomento]. AB - Research was made on the presence of mosquitoes (Diptera: Culicidae) in the Fomento municipality health areas attended to by 52 family doctors, in Sancti Spiritus Province. 19 species were found. Culex quinquefasciatus and Anopheles albimanus were the most widely found. Fish and aquatic insect species serving as biological regulators were determined in each reservoir. The Gambusia punctata was the larvivorous fish most frequently found and most widely disseminated. Among predacious insects, those of the Odonata and Hemiptera orders were the most widely found. PMID- 7984820 TI - [The National Toxoplasma Survey. I. Prevalence by sex and age. Cuba, 1987]. AB - A national seroepidemiological survey was carried out to assess the prevalence of anti-Toxoplasma gondii antibodies. 8863 samples taken in filter paper through the ELISA test were analyzed and 29.70% positivity was obtained. No significant differences were found regarding sex. Seropositivity increased with age, up to the 20-29 age group, with a stable behavior in over-29-year age groups. The highest percentage of annual change was registered in the 5-9 age group (1.62%). This parameter reached 0.93% in the women's 25-29 age group. PMID- 7984822 TI - [Biological control of the intermediate mollusk hosts of tropical diseases. A review of the different mechanisms observed and tested in the Western Hemisphere]. AB - A review of various methods for the biological control of tropical diseases intermediate host mollusks is presented. Our study is mainly based on experiences attained in the Western Hemisphere and, particularly, in the Caribbean. PMID- 7984823 TI - [Dengue fever and hemorrhagic dengue in infants with a primary infection]. AB - The aim of this work was to offer a description of the clinical manifestations developed by patients under 1 year who had dengue virus infection and dengue hemorrhagic fever during the epidemic which broke out in 1981, and to determine if the passive transfer of maternal dengue antibodies to the fetuses influenced the occurrence of a severe development of the disease, through a retrospective study. In 20 cases, type 2 dengue virus infection was confirmed. Eight patients showed the clinical manifestations of dengue hemorrhagic fever of dengue shock syndrome (DHF/DSS), and the other 12 had the typical dengue virus infection. The former were of the white racial phenotype, aged under 6 months. There was a predominance of type 1 dengue antibodies in the mothers of children with DHF/DSS. Fever, rash, vomiting and diarrheas (not frequent) appeared in the two clinical manifestations of the infection; blood leukocytes were predominantly lymphocytic; and erythrocyte sedimentation was always normal. Patients with DHF/DSS presented with some bleeding (87.5%); cyanosis and ascites (37.5%); and shock (25%), as well as hepatomegaly. All these infants with DHF/DSS had thrombocytopenia and most of them showed hemoconcentration. No deaths occurred. PMID- 7984824 TI - Myasthenia gravis: pathogenesis and treatment. AB - Much is known about the pathogenesis of MG. This information has provided a rational basis for treatment of the disease, which is very effective. On the other hand, present treatments are limited by significant adverse effects. Our knowledge of pathogenesis also provides clues for the development of new, effective, but less toxic treatments. In addition, knowledge of the autoimmune mechanisms in MG may be useful in devising better treatments for the many human autoimmune diseases that are less well understood. PMID- 7984825 TI - Lambert-Eaton myasthenic syndrome: pathogenesis and treatment. PMID- 7984826 TI - Evaluation and treatment of patients with neuropathy and monoclonal gammopathy. PMID- 7984827 TI - Guillain-Barre syndrome and chronic inflammatory demyelinating polyneuropathy: pathogenesis and treatment. PMID- 7984828 TI - How to diagnose and treat the inflammatory myopathies. AB - The inflammatory myopathies include 3 distinct entities, PM, DM, and IBM. These diseases differ clinically, immunopathologically, and in their response to therapies. Although DM and IBM are easy to diagnose on the basis of characteristic clinicopathologic findings, PM still remains a diagnosis of exclusion. A T cell-mediated cytotoxic process in PM and IBM and a complement mediated microangiopathy in DM, along with the various serologic markers of autoimmunity, are the hallmarks of the underlying autoimmune processes in these groups. Although in uncontrolled studies PM and DM appear to respond to prednisone and immunosuppressive drugs to some degree and for some period of time, IBM is resistant to all therapies. Currently, high-dose intravenous immunoglobulin (IVIG) appears to be an encouraging and safe new modality of treatment for some of these conditions when other therapies have failed. In a controlled study, IVIG has been shown to be effective in DM and, in uncontrolled studies, in some patients with PM or IBM. PMID- 7984830 TI - Stiff-man syndrome. PMID- 7984829 TI - Multiple sclerosis: pathogenesis and treatment. PMID- 7984831 TI - Vasculitis: diagnosis and therapy. PMID- 7984832 TI - Antiphospholipid syndromes and the nervous system. Clinical features, mechanisms, and treatment. PMID- 7984834 TI - Even a blind hog. Robert J. Joynt, M.D., Ph.D. PMID- 7984833 TI - Paraneoplastic disorders: antineuronal antibodies and therapeutic options. PMID- 7984835 TI - Neuroimmunotherapy: a practical approach to the treatment of immune-mediated neurologic diseases. AB - Immunosuppressive drugs and immunomodulating procedures can improve the quality of life in patients with immune-related neurologic diseases, or even be life saving, if properly used to avoid deleterious or irreversible adverse effects. For the successful use of these drugs or procedures, the treating physician must be familiar and comfortable with the drugs' mode of action and consider some important principles: 1. The diagnosis must be secure before starting therapy. 2. It is essential to have a basic understanding of the immunologic dysfunction that is amenable to immunotherapy. 3. The goals and the expectations of therapy must be defined, and the risk/benefit ratio of the drugs or procedures must be well understood. 4. Improvement must be based on objective measurements of muscle strength and a beneficial change in activities of daily living, and not solely on a change in the laboratory test values. 5. The limitations of therapy and the time suitable for starting or stopping a drug should be clear to both the therapist and the patient. 6. The selection of a drug or procedure should be guided on the basis of current knowledge, preferably established in controlled trials. 7. Every effort must be made to prevent the development of adverse effects and to determine the lowest dose of a medication that controls the disease. 8. Drug interactions that can cause adverse effects and conditions that can worsen a disease must be avoided. PMID- 7984836 TI - [Silicosis and primary Gougerot-Sjogren syndrome]. AB - We report three cases of primary Sjogren's syndrome in silicotic coal miners. All patients fulfilled the diagnostic criteria for Sjogren's syndrome recently established by the European Community study group. One patient had cryoglobulinemia and polynevritis. Another had Raynaud's phenomenon, arthralgia, purpura and polynevritis. Capillary microscopy was normal in all the three patients. Antinuclear antibodies were detected only in one patient, who had also anti-SSa and anti-SSb antibodies. The prevalence of systemic sclerosis, rheumatoid arthritis and probably systemic lupus erythematosus is significantly higher after longstanding occupational exposure to silica. On the contrary, any case of Sjogren's syndrome was till now described in the course of pulmonary silicosis. The physiopathological mechanisms of these associations are misunderstood. PMID- 7984837 TI - [Aging and procedural memory. Study of a series of tests on microcomputers]. AB - The authors have assessed perceptual motor tasks involving the learning of the mouse control by locking at a Macinthosh computer screen during three consecutive sessions. Tests were performed by 102 control subjects aged between 16 and 85 years. Concerning age, there was a significant time difference (ANOVA) but improvement was the same for all subjects. Educational level and IQP results didn't influence procedural performance. Men were faster in three tasks. We can argue that implicit learning abilities appear before explicit memory and within the adult life span there appears to be little significant deterioration in implicit memory abilitie. PMID- 7984838 TI - [Portal vein thrombosis: a rare complication of Crohn disease]. AB - Among usual extra digestive manifestations of inflammatory bowel diseases, vascular injuries are rare, but often of excessive gravity. The emergence of a portal thrombosis, often accelerated by infection or traumatism, particularly surgical, remains exceptional. We report the case of a young patient who is followed for a severe crohn's disease and affected with a brutal portal vein thrombosis. Although initial prognosis was bad, the patient now lead a normal life ten months after this episode. It's the third described case of portal thrombosis in crohn's disease. We discuss the predisposing role of an acquired protein S deficiency during a estroprogestative treatment. PMID- 7984839 TI - [Tricuspid insufficiency disclosing carcinoid syndrome]. AB - The authors present a case of tricuspid regurgitation which reveals a carcinoid syndrome in an 68 year-old woman discovered in view of right heart failure. This carcinoid heart disease is early without symptoms of the primitive or the liver metastatic tumors. We see a good evolution with somatostatin's analogue. We review the diagnosis features in trans-thoracic and trans-oesophageal echocardiography, and the possibility of surgical treatment of these lesions. PMID- 7984840 TI - [Clostridium perfringens septicemia in drug-induced aplasia]. AB - Septicemia due to Clostridium perfringens during the course of acute leukemia is rare and often lethal particularly in childhood. Antibiotherapy is necessary but polymorphonuclear activity recovery is helpful. This can be done through transfusion or administration of colony stimulating factors. Here is a new case of such a septicemia in a 12 year-old female treated for acute lymphoblastic leukemia. Of particular interest is the favourable outcome despite a high risk situation. PMID- 7984841 TI - [Sjogren's syndrome and virus]. AB - Virus are suspected to play a role in triggering lymphoid proliferation observed in Sjogren's syndrome (SS). In this paper, attention is focused on the potential role of herpes virus, retrovirus and hepatitis C virus (HCV) in the pathogenesis of SS. Genes and proteins of Epstein-Barr virus (EBV) are detected in epithelial cells of salivary or lacrymal glands more often in SS patients than in controls. However, it could just be a consequence of the destruction of the glands by another mechanism. Endogenous retroviral sequences are detected with a high frequency in salivary glands of SS patients, than in controls. Sicca syndrome may occur in HIV, HTLV-I and HCV-infected patients. We found the expression of the tax gene of HTLV-I in epithelial cells of salivary glands from two patients without any evidence of HTLV-I-associated disease and without any seric anti-HTLV I antibodies. Anti-SSA and anti-SSB antibodies are usually not detected in serum of patients with sicca syndrome occurring during evolution of recognized viral diseases. Thus, this kind of sicca syndrome could be a little different from classical auto-immune SS. However, it is tempting to consider oropharynx like a site of latency of a lot of virus which could infect salivary epithelial cells. In some people with a particular genetic background, this could lead to a lymphoid proliferation and, secondary, to the destruction of the glands. PMID- 7984842 TI - [The stakes of the general knowledge curriculum in the first year of medical school (CPEM 1)]. PMID- 7984843 TI - [A retroperitoneal mass]. PMID- 7984844 TI - [Bone non-Hodgkin's lymphoma, of pseudomyelomatous manifestations, in AIDS]. PMID- 7984845 TI - [Dementia-depression: how are they related? From depressive pseudodementia to pseudodepression in dementia]. AB - Dementia and depression are among the most frequent and disabling conditions in the elderly. The prognosis of depression is similar in young and elderly patients; however, treatment can be more risky in the latter. Incorrect diagnosis of dementia as well as therapeutic relentlessness should be avoided. An attempt is made to clarify the ways dementia and depression can combine. The reality of pure depressive pseudodementia seems doubtful. Depression can worsen a dementia. Cognitive dysfunction can be observed in depression, though it is difficult to estimate the extent and the meaning of this association. Patients with very mild dementia are often referred for a depression, which is ruled out by careful examination. There is no simple mean to differentiate dementia from depression. The proper way remains to perform a strict clinical, neuropsychological and psychiatric examination. PMID- 7984846 TI - [Normal mourning and pathological mourning]. AB - The mourning's function and the usual phases of this process are described. Complicated and pathological kinds of mournings are analysed, as well as their inducing circumstances. Adequate behaviours about the therapeutic relation are discussed. PMID- 7984847 TI - [Pharmacological treatment of depression]. AB - Major depression is a frequent and incapacitating illness. Recent research has established its natural course, often characterised by chronicity or recurrent episodes, leading to long-term pharmacotherapy. Effective pharmacologic treatments are available for depression, including tricyclic antidepressants, monoamine oxidase-inhibiting agents, and newer medications. Successful pharmacotherapy for depression requires consideration of the profile of the antidepressant drugs, to balance their therapeutic effects and side effects profiles. PMID- 7984848 TI - [Chronic fatigue syndrome]. AB - The major and minor diagnostic criteria of the chronic fatigue syndrome are described. The stages of the differential diagnosis, the diagnostic strategies and the controversies, while insisting on certain sleeping disorders are discussed. The cause of the syndrome may be a viral infection, and an anxious depressive state may increase somatic complaints. Patients with chronic fatigue syndrome did not demonstrate a specific response to therapy. Spontaneous remission after a few years is a typical feature of this syndrome. PMID- 7984849 TI - [Bacterial endotoxins: a pathogenic factor in asthma?]. AB - Though the house dust mite allergen is considered as one of the most important factors in perennial asthma, several observations suggest that it could be but one of several factors leading to asthma. Exposure to bacterial endotoxins has been associated with some occupational chronic obstructive bronchial diseases. In the present work, endotoxins were measured in the house dust, and observations of the skin and bronchial challenge tests as well epidemiological studies suggest that they play a role in asthma. PMID- 7984850 TI - [Laparoscopy: new technique in urology]. AB - Laparoscopic surgery in urology is in a testing and development phase. The technique is currently used by some urologists to evaluate non-palpable testes and to perform varicocelectomy or pelvic lymphadenectomy. Other standard open surgical procedures are experimentally being performed with the laparoscope. Owing to technological advances laparoscopic surgery might become a part of routine urological care. We review the current impact of laparoscopy on urology, we emphasise the advantages but also the risks of this new approach, and discuss the benefit of these technical feats. PMID- 7984851 TI - [Assessment of functional status in general medicine: the COOP/WONCA indices]. PMID- 7984853 TI - [Urinary incontinence. Rehabilitation]. PMID- 7984852 TI - [Radiological puzzle. Intracerebral cavernous hemangioma]. PMID- 7984854 TI - [Surgery of urinary incontinence. Treatment in women]. PMID- 7984855 TI - [Treatment in men]. PMID- 7984856 TI - [Surgery of urinary incontinence. Role of the operating room nurse]. PMID- 7984857 TI - [Urinary incontinence in the adult. Epidemiology and therapeutic indications]. PMID- 7984859 TI - ["Biotrol System 2". Contribution on a two piece collecting system with security lock in the life of a stoma patient]. PMID- 7984858 TI - [Treatment of wounds]. PMID- 7984860 TI - [Urinary incontinence. Complementary examinations]. PMID- 7984861 TI - [Urinary incontinence. Drug therapy]. PMID- 7984863 TI - [Nursing care in the operating room. Adenoidectomy, paracentesis, transtympanic drainage]. PMID- 7984862 TI - [Short procedures in otorhinolaryngological surgery. Problems with anesthesia]. PMID- 7984864 TI - [Operating room nursing. Endoscopic balance, amygdalectomy, laser CO2]. PMID- 7984865 TI - [Nursing at the otorhinolaryngological service. Amygdalectomy and adenoidectomy. Plan of care]. PMID- 7984866 TI - [New technique; new organization]. PMID- 7984867 TI - [Endotracheal intubation]. PMID- 7984868 TI - [Ambulatory surgery in otorhinolaryngology. Adenoidectomy, transtympanic aerator, amygdalectomy]. PMID- 7984869 TI - [Prostate. Surgical anatomy and access pathways]. PMID- 7984870 TI - [Paranasal sinus endoscopy]. PMID- 7984871 TI - [Ambulatory surgery in otorhinolaryngology. The laser]. PMID- 7984872 TI - Aryl hydrocarbon or dioxin receptor: biologic and toxic responses. AB - 1. The AhR represents a ligand-activated transcription factor. Receptor agonists include planar aromatic compounds, a variety of heterocyclic plant constituents, and PCDD/PCDF. The latter lead to persistent activation of the receptor due to their strong binding affinity and long biologic half-life of over 10 years in human blood and fat. Practically every person on earth is exposed to these compounds via the diet (> 90%) and by high concentrations in mother's milk. PCDD/PCDF produced toxic responses in exposed people (primarily chloracne and immunosuppression) in the past. However, the present PCDD/PCDF levels (basal levels) in the general population are below those warranting toxicologic concern. 2. The AhR has been characterized as a helix-loop-helix transcription factor related to the Drosophila developmental genes sim and per. The cytosolic form of the receptor is present as an inactive complex with two subunits of HSP90. After ligand binding HSP90 is released and the receptor enters the nucleus as a heterodimer together with a related protein ARNT. It binds with high affinity to certain enhancer elements in the upstream region of several genes such as cytochrome P4501A1 (CYP1A1). The AhR transcriptionally activates several drug metabolizing enzymes and proteins involved in growth/differentiation, such as the plasminogen activator inhibitor PAI-2 and IL-1 beta. In addition, it modulates the action of a number of other nuclear transcription factors such as receptors of the steroid hormone receptor superfamily and of cell surface receptors such as EGF. With the exception of CYP1A1 induction, little is known about the mechanism of transcriptional activation of the AhR-controlled genes. Many AhR-modulated biologic responses (such as modulation of the estrogen and EGF receptor) appear to be indirect. 3. Persistent activation of the AhR is probably responsible for toxic responses in experimental animals and humans. They are markedly tissue and species specific. In rodents a wasting syndrome, immunosuppression, teratogenicity, chloracne, and carcinogenicity/tumor promotion have been well studied. There is good evidence for an involvement for the AhR in these responses. However, the chain of events from receptor activation to the diverse toxic endpoints is largely unknown. Alteration of growth and differentiation of epithelial tissues may underlie most of the toxic responses. A lot has already been achieved, mostly by characterizing the AhR and transcriptional activation of CYP1A1. Still more work lies ahead of us, for example, elucidation of the physiologic roles of the AhR and of the chains of events from receptor activation to the various biologic and toxic endpoints. PMID- 7984873 TI - Calcium as modulator of phototransduction in vertebrate photoreceptor cells. PMID- 7984874 TI - Physiological and metabolic responses to hypoxia in invertebrates. PMID- 7984875 TI - Incorrect adjustment may render study results inaccurate. PMID- 7984876 TI - Ethics in action: a preop mastectomy patient who knows a little about therapeutic touch. PMID- 7984877 TI - When your patient has ovarian cancer. PMID- 7984878 TI - Taxol--new hope for cancer patients. PMID- 7984879 TI - New parameters for cholesterol screening. PMID- 7984880 TI - Preventing needlesticks. A market survey. PMID- 7984881 TI - Preventing needlesticks. One hospital's solution. PMID- 7984882 TI - Gastrostomy and jejunostomy tubes. PMID- 7984883 TI - Violence in the workplace: you're entitled to protection. PMID- 7984885 TI - It's what we do. PMID- 7984884 TI - Evaluating elevated blood sugar in diabetic patients. PMID- 7984886 TI - [Do women still die in childbirth in France?]. PMID- 7984887 TI - [Proton pump inhibitors in the treatment of reflux esophagitis]. PMID- 7984888 TI - [Non-schizophrenic chronic delusions]. PMID- 7984889 TI - [Dermatitis herpetiformis]. PMID- 7984890 TI - [Creutzfeldt-Jakob disease and pituitary extracts]. PMID- 7984891 TI - [Assassination of President Sadi Carnot]. PMID- 7984892 TI - [Pathogeny of sarcoidosis]. AB - Sarcoidosis is a multisystemic granulomatous disorder due to an immune response of unknown etiology. The interactions between monocytes/macrophages and T lymphocytes through direct contact between the cells play a major role in the occurrence of these responses. Factors depending on the host, such as the polymorphism of the major histocompatibility complex molecules could be implicated in sarcoidosis pathogenesis. The factors that regulate the degree of granulomatous reaction, or those that determine the degree of fibrous response observed in some patients with sarcoidosis are poorly understood. Two recent studies, using the high sensitivity of the polymerase chain reaction, have shown the presence of M. tuberculosis DNA in 13 to 50% of biopsy samples from sarcoid patients, suggesting a role of this agent in the disease, at least in certain cases. PMID- 7984893 TI - [Clinical and paraclinical of mediastinal-pulmonary sarcoidosis]. AB - Radiographic and clinical manifestation of mediastinal pulmonary sarcoidosis depend on a number of factors, particularly ethnic origin, and especially the type of chest radiographic change. Clinically, the physician takes into account the age of the patient, the frequent discordance between the absence or presence of only slight functional respiratory signs and discrete alterations of respiratory function on the one hand, and the severity of thoracic lesions on radiography, the presence of hilar and (or) mediastinal adenopathy and occasional extrathoracic localisations. Elevated serum levels of angiotensin converting enzyme, CD4+ T lymphocytosis in the broncho-alveolar lavage fluid and increased pulmonary GA-67 uptake reflect disease activity but are not prognostic. The key to diagnosis is histology. Such diagnosis requires demonstration of noncaseating tuberculoid granuloma, and exclusion of all other aetiologies capable of inducing such a histological lesion. Data obtained by clinical observation, radiography, scanning and functional respiratory and laboratory tests are not, in most cases, predictive of the course. PMID- 7984894 TI - [Thoracic imaging in the diagnosis and surveillance of sarcoidosis]. AB - Imaging is useful at all stages of management of thoracic sarcoidosis. It contributes to diagnosis, prognosis, evaluation of lesions and follow-up in the course of the disease. Chest radiography is essential in initial work-up as well as during the course of well-tolerated forms of the disease. High resolution CT and gallium-67 scintigraphy are useful in severe lung involvement and in chronic forms of sarcoidosis. PMID- 7984895 TI - [Cutaneous manifestations of sarcoidosis]. AB - Skin involvement in sarcoidosis is common and may occur as very early symptoms. Since skin biopsy is easy, these manifestations allow a rapid diagnosis. Erythema nodosum is a non specific symptom, and rare other non specific manifestations may occur. Skin lesions are mostly specific, with an epithelioid granuloma, lack of classification and a few giant cells. The clinical spectrum is very large, and the diagnosis is often made with regards to histopathological features only. PMID- 7984896 TI - [Eye manifestations of sarcoidosis]. AB - Ophthalmologic manifestations of sarcoidosis are multiform, and all parts of the structure of the eyeball can be affected. Involvement of the conjunctiva and of the lacrimal glands is the most frequent and is benign. Uveitis is observed in 20% of patients. It is generally torpid, evolving in chronic fashion. The possibility of uveitis requires routine investigation in all patients with sarcoidosis. Neuro-ophthalmologic involvement is rare but severe. When isolated, it presents difficult problems of diagnosis. PMID- 7984897 TI - [Severe extrapulmonary forms of sarcoidosis]. AB - Severe extrapulmonary sarcoidosis mainly consists of cardiac and neuromuscular involvement, both of which compromise the functional prognosis and survival. Their rare occurrence is a major factor in delayed diagnosis and treatment when they are the presenting signs of the disease, and especially when not associated to the "classic" signs of sarcoidosis. The lack of clinical and paraclinical specificity hinders diagnosis, and in the absence of histological evidence, all clinical and paraclinical factors compatible with sarcoidosis must be taken into account. Since these localisations are often asymptomatic or poorly symptomatic, they should be routinely sought by careful clinical examination and electrocardiogram. The presence of such signs modifies the therapeutic approach and requires treatment with corticosteroids. PMID- 7984898 TI - [Choice and contribution of biopsy in sarcoidosis]. AB - The diagnosis of sarcoidosis is made on both the clinicoradiological presentation and characteristic pathologic features. The pathologic proof is necessary for diagnosis, and is obtained by biopsies as little aggressive as possible, directed by the clinicoradiologic manifestations of the disease, which are often thoracic, bronchial, pulmonary or ganglionnary. PMID- 7984899 TI - [Biological tests in sarcoidosis: contribution to diagnosis and surveillance]. AB - No single laboratory examination is diagnostic. On the other hand, such examinations support the diagnosis and aid in management of treated patients. In the serum, there is lymphopenia with a lowered CD4/CD8 ratio. An increase in beta 2-microglobulin and in the soluble IL-2 receptor reflect T lymphocyte activation. A classic observation is hypercalcaemia with hypercalciuria. The increase in angiotensin I converting enzyme reflects the body granulomatous mass. The results of bronchoalveolar lavage show the characteristics of the alveolitis associated with granulomatosis, accumulation of CD4+ T lymphocytes and activated alveolar macrophages. In practice, biochemical anomalies are of interest in the follow-up of treated patients. PMID- 7984900 TI - [Treatment of sarcoidosis]. AB - The treatment of sarcoidosis remains empirical. In severe cases, it is based on systemic corticosteroid therapy which is highly effective on granulomatous lesions and immune and metabolic disorders. Its limitations are its purely "suspensive" effect, its lack of efficacity on fibrous lesions and its side effects. It is widely accepted in the case of poorly tolerated, recent sarcoidosis and respiratory or extrarespiratory involvement, modification of the general status, or hypercalcaemia. In these cases, its therapeutic effect is spectacular. Corticosteroid treatment is also indicated in most chronic forms having development of fibrosis. Complementary examinations, especially CT scan of the chest, can be useful in treatment decision. Failure or contraindication of corticosteroids suggests the use of synthetic antimalarial drugs or methotrexate. Local corticosteroids are useful in treatment of ophthalmologic or skin localisations. PMID- 7984901 TI - [Splenomegaly. Diagnostic orientation]. PMID- 7984902 TI - [Respiratory distress in newborn infants. Positive diagnosis, emergency treatment]. PMID- 7984903 TI - [Circulatory arrest. Diagnostic orientation and emergency treatment]. PMID- 7984904 TI - [Anemia. Diagnostic orientation]. PMID- 7984905 TI - [Persisting fever (more than 20 days). Diagnostic orientation]. PMID- 7984906 TI - [Mumps. Epidemiology, diagnosis, course, prevention]. PMID- 7984907 TI - [Pelvic pain. Diagnostic orientation]. PMID- 7984908 TI - [Substitution criteria in therapeutic trials]. PMID- 7984909 TI - [Acyclovir and infections caused by varicella-zoster viruses]. PMID- 7984910 TI - [Electroshock therapy today]. PMID- 7984911 TI - [Voronoff's hormonal utopia. Endocrinology in mythological times]. PMID- 7984912 TI - [Epidemiology of primary bacterial meningitis]. AB - In industrialized countries, the incidence of community-acquired bacterial meningitis is between 5 and 10 cases/10(5) population/year. The highest age specific attack rates are recorded between 0 and 2 years of age and can reach 100 cases/10(5) population/year or more in some countries. In this range of age, Streptococcus agalactiae, Listeria monocytogenes and Escherichia coli are responsible for meningitis in neonates whereas Haemophilus influenzae, Neisseria meningitidis and Streptococcus pneumoniae cause meningitis in children older than 1 month. H. influenzae was the leading cause of bacterial meningitis in children but its incidence has declined since the introduction of routine childhood immunization with conjugate vaccines. N. meningitidis is the leading cause of meningitis in teenagers and young adults, whereas S. pneumoniae is responsible for most of meningitis in the elderly. Prognosis of bacterial meningitis mainly depends on the type of causative organism and on the age of onset. Detailed epidemiologic features of Haemophilus, meningococcal and pneumococcal meningitis are provided. PMID- 7984913 TI - [Contributions of experimental models to the physiopathology and treatment of bacterial meningitis]. AB - Access to the cerebrospinal fluid, which is the only objective reflection of the essential parametres, is very limited. Investigators have long tried to design an animal model. Presently, the experimental model of the newborn rat is most often used for studying pathogenic factors in haematogenous meningitis. In contrast, the rabbit model is more adapted to therapeutic investigation The main advances have been therapeutic and pathophysiologic. Good examples are the identification of optimum antibiotic levels in the cerebrospinal fluid, and the demonstration of the responsibility of mediators produced by the host in triggering the inflammation. The principle of corticosteroid treatment before induction of bacterial lysis by antibiotics in Haemophilus meningitis is a result of such work. PMID- 7984914 TI - [Treatment of bacterial meningitis in newborn infants and children]. AB - Third generation cephalosporin as cefotaxime or ceftriaxone is the best first line treatment. Duration of treatment is 7 to 10 days in uncomplicated disease. Dexamethasone used very early--before or at the same time of the antibiotic injection--seems to decrease sensorial sequelae. Amikacin by IV route, decreases short term complications. For bacterial meningitis due to intermediate penicillin pneumococci, an increase in daily dose of beta-lactamin is recommended; for resistant pneumococci, vancomycin by continuous infusion and with large doses is used. Chemoprophylaxis by rifampicine is effective for both Meningococcus and Haemophilus. Haemophilus influenzae b vaccination will decrease systemic infection due to this pathogen. In newborns, morbidity is higher, due in part to brain abscesses. Therapeutic choice is not the same for materno-foetal and postnatal infection. Antibiotherapy duration is, at least, 15 days and 21 days for gram-negative bacteria. PMID- 7984915 TI - [Epidemic bacterial meningitis in adults and the elderly]. AB - Epidemic bacterial meningitis in the adult and the elderly are essentially due to Streptococcus pneumoniae. Neisseria meningitidis and Listeria monocytogenes. Their poor prognosis is mainly due to the severity of the associated encephalitis, responsible for neurological sequelae and for mortality ranging from 20 to 30% in pneumonococcal and Listeria meningitis. Treatment associates an antibiotic having rapid antibactericidal action in the CSF, suppression of possible foci of primary infections and intensive care required by the frequency of associated visceral insufficiency. Present research is centered on: 1. the appearance and progression of pneumococcal lines resistant to penicillin; 2. the trials of modulators of the inflammatory response, notably dexamethasone; 3. the improvement of antibiotic concentrations in the CSF and the cerebral parenchyma, particularly in listeria infection. PMID- 7984916 TI - [Acute viral meningitis]. AB - Viral meningitis are the most frequent cause of clear cerebrospinal fluid (CSF) meningitis and are usually benign. The viral nature is suggested by clinical arguments (context, associated manifestations) and particularly the analysis of CSF, typically lymphocytic. However, problems of CSF interpretation may occur during the polymorphonuclear reaction at the beginning of such meningitis and after elevated protein or low glucose concentration. The main differential diagnosis are: partially treated bacterial meningitis, the beginning of meningococcal meningitis, listeriosis or tuberculous meningitis which need and urgent and specific treatment. The most common agents are the enteroviruses. The etiology can only be detected through careful virological investigations. These studies may be useful in outbreaks or in epidemiological studies. PMID- 7984917 TI - [Meningo-encephalitis with clear cerebrospinal fluid in adults]. AB - Meningitis with a clean cerebrospinal fluid are most often benign and related to a wide variety of viruses with spontaneous favourable outcome. Measles and rubella are dramatically decreasing, because of the systematic vaccination. The main problem is heptic meningoencephalitis, leading to an empiric treatment with aciclovir. The other urgent question is the possibility of Listeria infection, leading also to an empiric antibiotherapy. Tuberculosis should not be neglected, but the treatment is not so urgent. The various hypotheses are often formulated because of epidemiological data or underlying disease. The biological data are most often too late to be interesting for the initial therapeutic decision. PMID- 7984918 TI - [Diagnosis of cerebro-meningeal infections after travel abroad]. AB - Cerebromeningitis after travel abroad is often acute and febrile and is a serious event. The most frequent and severe cause is pernicious malaria due to Plasmodium falciparum; diagnosis is rapid by thick blood film and thin blood smear; it requires specific emergency treatment. Many other aetologies exist but they are rare; they must nonetheless be considered, keeping in mind that cosmopolitan infections can be favoured by travel conditions. PMID- 7984919 TI - [Cerebro-meningeal infections in patients with human immunodeficiency virus infections]. AB - Opportunistic infections of the central nervous system, frequent in AIDS, present essentially in 4 clinical pictures: brain mass lesion(s), meningitis, diffuse encephalitis or prolonged fever. Toxoplasmosis is by far the most frequent cause of brain mass lesion. Therefore, for patients presenting with a brain mass lesion it is recommended to start presumptive antitoxoplasmic therapy with the combination of pyrimethamine and sulfadiazine. Other etiologies (lymphoma and progressive multifocal leukoencephalopathy) should be considered only after failure of this treatment. The other infectious processes are much more uncommon (cryptococcoma, tuberculoma, Candida, Nocardia abscesses). In case of meningitis, cryptococcosis must be searched for, in addition to classic causes of meningitis. Diffuse febrile encephalitis should lead to consider presumptive antitoxoplasmic therapy. Finally, prolonged fever can be the only expression of cerebral toxoplasmosis or cryptococcal meningitis. PMID- 7984920 TI - [Cerebro-meningeal infections and immune deficiencies, excluding AIDS]. AB - Infection of the central nervous system is generally a serious event due to the risk of fatality and the possibility of sequelae. In immune deficient patients, there is a relatively large range of infectious agents that may be responsible for meningoencephalitis or a cerebral lesion, and determining aetiology can be difficult. In some cases, the agent is isolated from the CSF or from a peripheral site, which permits rapid, appropriate treatment. In other cases, when a direct neurosurgical approach to the lesions is precluded, the main elements determining the best probable treatment are the nature of the immunodeficiency and especially results of imaging investigation. PMID- 7984921 TI - [Cerebral abscess and empyema]. AB - Brain abscess and subdural empyema are serious infections which can be metastasis of chronic suppurative diseases (bronchectasia, lung or abdominal abscesses) or of congenital cardiopathy, but they are more frequently seen in healthy adults suffering from chronic sinusitis or otitis. Brain CT scan with contrast media injection is the best tool for diagnosis and follow-up. It has transformed the prognosis of brain abscesses. Anaerobic oropharyngeal microflora is the main source of bacteria responsible for suppurative brain diseases. Surgical treatment consists of aspiration or, rarely now, of excision of the lesion. Medical treatment alone can be successful in selected cases, provided patients are closely monitored and antibiotics with good penetration into the brain parenchyma are used. PMID- 7984922 TI - [Iatrogenic and traumatic cerebro-meningeal infections]. AB - Nosocomial cerebro-meningeal infections have a severe prognosis and are increasing infrequence. Main causes are neurosurgical procedures, ventriculostomies, head trauma and rarely peridural anaesthesia and lumbar punctures. The diagnosis is usually difficult because of the poor specificity of the clinical and laboratory signs. Predominant pathogens are gram-negative bacteria (including Enterobacteriaceae and Pseudomonas) and staphylococci (including Staphylococcus epidermidis). Treatment is based on the use of 3rd generation cephalosporins and sometimes imipenem. An alternative choice is the use of 2nd generation quinolones. If staphylococci are suspected, vancomycin, alone or in combination is prescribed. PMID- 7984923 TI - [Tuberculous meningitis]. AB - The incidence of tuberculosis has been increasing since 1985. Favourable host factors associated with non specific neurologic abnormalities must lead to the hypothesis of a meningeal tuberculosis. Blood analysis and radiological findings rarely contribute to the diagnosis. The diagnosis is established when tubercle bacilli are identified in the cerebral-spinal-fluid, sometimes immediately but most often after 4 to 6 week culture. New faster methodes are being developed, but they are not yet routinely available. The treatment must be started before the identification of the tubercle bacilli. Usually, for immunocompetent patient, short-course treatment is chosen, consisting of an initial 2-month intensive treatment (rifampycin, isoniazid, and pyrazinamide) followed by a 4-month maintenance therapy with isoniadid and rifampicin, ethambutol should be included systematically during the first 16 weeks in prevention of isoniazid resistance. PMID- 7984924 TI - [Acute appendicitis. Pathological anatomy, diagnosis, treatment]. PMID- 7984925 TI - [Complications of acute appendicitis. Diagnostic, treatment]. PMID- 7984926 TI - [Primary bronchopulmonary cancers. Epidemiology, pathological anatomy, etiology, diagnosis, course, treatment]. PMID- 7984927 TI - [Cutaneous ectoparasitic infestations: scabies. Epidemiology, diagnosis, treatment]. PMID- 7984928 TI - [Foci of dental infections and their complications. Etiology, diagnosis, course, prognosis, treatment]. PMID- 7984929 TI - [Hemorrhage at delivery. Diagnosis, treatment]. PMID- 7984930 TI - [A new approach of digestive hemorrhage related to portal hypertension]. PMID- 7984931 TI - [Spasticity: current therapeutic methods]. PMID- 7984932 TI - [Campaign against alcoholism in France (1870-1918)]. PMID- 7984933 TI - [40 years of psychopharmacology]. PMID- 7984934 TI - [Antidepressive agents of recent generation]. AB - In the last decade, progress in psychopharmacology had led to the synthesis of newer antidepressant compounds. Known as "new generation antidepressants", they belong either to classical families of anti-depressants (tricyclics or MAOIs) or to new pharmacological groups. The first ones differ from classical tricyclics or classical MAOIs for the absence of major contraindications for their use (mostly few or no anticholinergic properties for new tricyclics and no dietary restriction rules for new MAOIs). The nontricyclics-non MAOIs antidepressants are, for most of them, particularly well tolerated and safe. The clinical potency of such compounds seems to reach conditions beyond depressive states and they have indeed some specific effects in obsessive-compulsive disorders or other anxiety disorders. In this group, selective serotonin reuptake inhibitors seem to represent a major progress in antidepressive therapy. All these advantages invite now the practitioners to use these "new generation antidepressants" as the first choice medication, when treating uncomplicated depressive disorders. PMID- 7984935 TI - [Antidepressive agents in non-depressive disorders]. AB - The evaluation of effect of psychotropic medications required clarification of operating diagnostic and of scales sensitive to change. In a second time, these allowed to demonstrate that some antidepressant agents act on pure obsessive compulsive disorder and on pure panic disorder, i.e. without associated depression. These antidepressants below to different chemical families, but their common action is to act on two main synaptic transmissions: the noradrenergic and the serotoninergic paths. PMID- 7984936 TI - [What should be the duration of a treatment with antidepressive agents?]. AB - The main clinical factors involved in deciding the length of an antidepressant treatment are briefly reviewed in the framework of current classifications of affective disorders. History of previous episodes and the polarity of depressive illness have a major role in such a process. Current definitions of remission, relapse and recurrence are given. In the context of a single depressive episode, treatment must be continued for at least 4 months after the start of clinical improvement in order to prevent a relapse. In case of recurrent depressive episode, the indications of a long-term treatment must be discussed. Some issues unsettled as to the adequate dosage of such a treatment, as well as to the length of treatment in other types of depressive states. PMID- 7984937 TI - [Mood regulator agents (excluding lithium)]. AB - Several anti-epileptic drugs have been shown to have a thymoregulatory effect and are thus alternatives to lithium treatment. They are mainly carbamazepine and, to a lesser degree, valproate (the use of clonazepam is only anecdotal in this indication). Their indications and contraindications are different from those of lithium, and they are highly useful in treatment. In addition, prescription is easy and tolerance good as long as precautions are respected and laboratory surveillance affords early detection of rare liver or blood complications. PMID- 7984938 TI - [New antipsychotic agents]. AB - In the eighties, the notions of refractory schizophrenia and of atypical neuroleptics have been described. An "atypical" neuroleptic is an effective antipsychotic drug without inducing concomitant extrapyramidal side effects. The concept of atypicity has become a new vista for research of new antipsychotic drugs. The notions of partial dopaminergic agonism, antagonism of D4 receptor, selective 5HT2 antagonism must be viewed as a source of future research and therapeutic improvement. PMID- 7984939 TI - [A new generation of tranquilizing agents]. AB - The newer anxiolytics include compounds whose the molecular structure, the mechanisms, and the pharmacological properties are heterogeneous. Nevertheless, the most of them have clinical and adverse effects like to the most known: buspirone, after the commercial shrinking for hepatic toxicity of alpidem. These anxiolytics are efficacious against generalized anxiety disorder, like the benzodiazepines. The principal interest consists in minimal adverse effects and the safety of the use. These compounds have not a sedative effect, do not induce rebound, dependence, abuse and withdrawal, do not impair the psychomotor, cognitive and memory performances. The big ratio efficacy/tolerance allows to use them in long treatments, old subjects, alcoholic and drug-addicted patients. Nevertheless to become ideal anxiolytics, these compounds must be efficacious in other anxious disorders and increase the efficacy of various psychotherapies. PMID- 7984940 TI - [Proper and improper use of benzodiazepines]. AB - Benzodiazepines are one of the most frequent treatments prescribed by the general practitioner, and anxiety disorders are one of the most important motives for consultation. Actually, benzodiazepines are effective and generally well tolerated. Nevertheless, the existence of adverse reactions such as dependence in addition to the importance of French consumption of benzodiazepines, necessitate the evaluation of good and bad use of benzodiazepines. Pharmacological specificities of benzodiazepines will be proposed in order to outline adverse reactions and contraindications. The authors will describe prescription modalities for benzodiazepines, in order to specify indications and how to get the best posology, frequency and length of treatment. PMID- 7984941 TI - [Drug dependence and psychotropic drugs]. AB - Although the utility of psychotropic drugs has been well demonstrated, caution must still be exercised in their use. Among their potential risks, drug dependency must be kept in mind. This risk is well accepted with regard to benzodiazepines, and it appeared useful to study the potential risk for antidepressants, neuroleptics and thymoregulatory agents. Whatever the drug, the predominant factor appears to be psychological dependency. Prevention of drug dependency is most often achieved by informing the patient, limiting the length of use of the drug, making regular reevaluation of symptoms and of drug indication, and frequently be establishing a "treatment contract". The importance of the patient-physician relationship in the prescription of such treatment must be underlined. PMID- 7984942 TI - [Cognition disorders related to psychotropic treatments]. AB - Evaluation of cognitive disorders induced by treatment with psychotropic drugs is complex due to the involvement of several factors that can intervene in the pathogenesis and the evaluation of these disorders. Nevertheless, studies are numerous in the field, and we present the main reports. Most studies evaluating the influence of psychotropic drugs in healthy subjects indicate the existence of cognitive changes. On the contrary, aside from the effect of tranquillizers, and the sedative effect and/or the anticholinergic action of certain psychotropic drugs, in treated patients the individual responsibility of these drugs in cognitive disorders appears to have been often overestimated. PMID- 7984943 TI - [Value of plasma assays of psychotropic drugs]. AB - An increased use of determinations of psychotropic drug levels has been noted during recent years. The contribution of "biological techniques" has led to a change in the relationship between physician and patient by rationalizing medical prescription and by augmenting the medical nature of this relationship. Follow-up of plasma levels is of interest for psychotropic drugs having therapeutic and (or) side effects that are linked to blood concentrations. Such drugs include the imipraminic antidepressants and regulators of thymic function. There is no consensus concerning the benzodiazepines and neuroleptic drugs. Their clinical effect does not seem to be strictly linked to plasma levels and the range of dosages is greater. Such determinations have proved to be particularly interesting in "resistant" cases, in surveillance of drug interactions and to evaluate treatment compliance. PMID- 7984944 TI - [Natural and synthetic antibacterial antibiotics. Principles and rules of use]. PMID- 7984945 TI - [Accidental hypothermia. Diagnosis, treatment]. PMID- 7984946 TI - [Acute abdominal pain in children. Diagnostic orientation]. PMID- 7984947 TI - [Low back pain. Diagnostic orientation]. PMID- 7984948 TI - [Anticancer chemotherapy (including hormone therapy). Classification, mode of action, main side effects]. PMID- 7984949 TI - [Epidemiology of collective infections and toxic infections originating from food or water. Methods of a survey in relation to an epidemic]. PMID- 7984950 TI - [Medical secrecy]. PMID- 7984951 TI - [Parasympatholytics. Principles and rules of use]. PMID- 7984952 TI - [Infectious temporomandibular arthritis. Apropos of a case in an adult]. AB - Imagery revealed osteitis of the base of the skull in a 37-year-old patient with infectious arthritis of the temporomandibular joint. The characteristics of this rare pathology were recalled from a review of the literature. PMID- 7984953 TI - [Amyloid disease and extreme macroglossia. Apropos of a case]. AB - A case of extreme macroglossia was observed in a patient with amyloid disease and dysglobulinaemia. A medial diamond-shaped glossectomy was required to reduce the size of the tongue. The details of the surgical and anaesthetic procedure are presented. This type of surgery, greatly appreciated by the patient, can only be undertaken after careful preparation. The reported cases are rare and the indication for surgery is difficult due to the unpredictable nature of the local and general clinical course of the disease. PMID- 7984954 TI - [Popliteal pterygium syndrome. A exceptional case]. AB - We report the case of a patient with a popliteal pterygium syndrome, a rare malformation associating, in its complete form, cleft lip and cleft palate, cleft lower lip, intergingival synechia, defects of the genito-urinary tract and popliteal pterygium. Based on this observation and a review of the literature, the phenotypic and genotypic aspects of this malformation were discussed together with adapted therapeutic management and genetic counselling. PMID- 7984955 TI - [Maxillary ameloblastoma. Apropos of a case and review of the literature]. AB - Although ameloblastoma is one of the benign odontogenic tumors, the maxillary localisations often grow more infiltratively and show higher recurrency than the mandibular localisations. The authors report a case of ameloblastoma in maxillary sinus and sketch out the operative methods with a literature review. PMID- 7984956 TI - [Mandibular metastasis disclosing a papillary carcinoma of the thyroid gland]. AB - The thyroid well differentiated carcinoma could be originate of the osseous metastasis and/or pulmonary or others. Sometimes, the cancer of the thyroid stay latent, discovered by the occasion of secondary osseous localisations. We bring back a personally observation of papillary cancer of the thyroid discovered by the occasion of mandibular metastasis. Helping ourselves by literary datum, we will comment on essentially the diagnostic and therapeutic problems breeded by this kind of metastasis. PMID- 7984957 TI - [American Burkitt's lymphoma with mandibular involvement]. AB - Burkitt's tumor is a undifferentiated lymphoma of lymphocytes B with a characteristic histologic pattern often called as "starry sky". It is classified in two groups: endemic Burkitt's lymphoma (African form), and non-endemic Burkitt's lymphoma (American form). The extranodal involvement of the head and neck in the American type is uncommon, so the diagnosis can be delayed. The authors present in this paper a case of American Burkitt's lymphoma in a patient with gingival hyperplasia, and compare the epidemiological, clinical, radiographic, therapeutic and prognostic characteristics of the endemic and non endemic forms of Burkitt's lymphoma. PMID- 7984958 TI - [Oculo-orbital anatomy and nuclear magnetic resonance: use in ocular growth and fetal pathology]. AB - The computation of eyeball growth has a wide field of applications in orbital and ocular pathology. An anatomic, macroscopic, histologic and RMI study has correlated the different oculo-orbital signals with the anatomy: a study of compute eyeball growth has been done. The anatomic study was made to determine the best MRI parameters to calculate the ocular surface. The surface was computed by MRI T2 weighted in the neuro-ocular plane in children aged from 0 to 13 years. The curve of eyeball growth shows rapid growth in utero until 18 months and then a phase of slower growth. A second study with fetuses RMI of pregnant women showed the neuro-ocular plane of fetus. Application in antenatal pathology are interesting. Two cases of orbital tumor, with fetal diagnosis are analysed and histologically explained. PMID- 7984959 TI - [Osteotomy of the median tubercule as a consequence of bilateral complete labio maxillo-palatal cleft]. AB - In the bilateral total labio-maxillary cleft the premaxilla is sometimes very protrusive at the completion of facial growth. This kind of malposition cannot be treated by orthodontics. Surgical repositioning of the premaxilla with simultaneous bilateral alveolar maxillary bone graft is done before the revision of lip and nose. Its goal is the reconstruction of a solid and harmonious dental and maxillary arch, closure of bucconasal fistulas, improvement of facial profile by closure of nasolabial angle. The authors describe the operation technique and illustrate it by two cases. PMID- 7984960 TI - [Lesions of the lingual nerve during extraction of the mandibular wisdom teeth. Consequences--etiopathogenesis--prevention--prognosis--legal medical aspects]. AB - A brief review of the lingual nerve anatomy is followed by an examination of the consequences of injury to the lingual nerve during mandibular wisdom tooth extraction on sensibility and sensorial activities. The circumstances of such injury are described as a function of the position of the tooth together with means of prevention. The clinical course of injury to the lingual nerve is unpredictable and varies over time and in quality of recovery. No prognosis can be made before a reasonable delay of 18 months to 2 years. Prevention remains the best treatment and consists of using a flexible bar to protect the nerve during the operation. Rate of legal disability compensation is estimated at 2 to 5%. PMID- 7984961 TI - [Historical development of the treatment of fractures of the middle third of the face involving occlusion]. AB - In the past decade principles of diagnosis and treatment of complex facial fractures have evolved dramatically. External appliances fixed to a headcap and semi-rigid immobilisation by wire suspensions which impose long term intermaxillary immobilisation have little by little disappeared. Conservative and often delayed fracture management has led to a more surgical and early approach in order to avoid difficult and often frustrating reoperations. The basic principles of fracture treatment are always based on re-establishing the occlusion to assume good function. The improvement in esthetic results are now derived from a better understanding of facial skeleton biomechanics, wide exposure of bony fragments and use of anatomic rigid internal fixation. Consequently, the duration of hospitalisation and job absence have been considerably reduced. This article reviews the historical steps from antiquity to present day, which mark the evolution of middle third fracture treatment. PMID- 7984962 TI - [Our experiences with cerebrospinal fluid rhinorrhea and its surgical treatment using an extracranial approach]. AB - The cerebrospinal fluid rhinorrhea is usually due to a skull lesion and is potentially dangerous for the patient, as it can be followed by an ascending meningitis. The extracranial approach (external ethmoidectomy, osteoplasty of the frontal sinus) has substituted craniotomy, especially in cases where the cerebrospinal fluid rhinorrhea is not due to intracranial lesions. In this study, we describe the surgical treatment of 9 patients treated in our clinic, and we make a brief review of the literature. PMID- 7984963 TI - Mandibular fractures treated by bone plating and intraosseous wiring. A comparative study. AB - We studied 79 cases of mandibular fractures treated with bone plates and 79 cases treated with intraosseous wiring. We encountered 3.8% major and 9% minor complications in the first group and 2.6% major and 31% minor complications in the second group. Bone plates were used in more complicated cases such as comminuted and infected fractures. It is our opinion that internal rigid fixation is a promising method of treating fractures of the facial skeleton, which is better tolerated by the patient but requires a certain experience. PMID- 7984964 TI - Proteus mirabilis bacteremia: a review of 176 cases during 1980-1992. AB - Patients with Proteus mirabilis bacteremia at a large community teaching hospital during a 13-year period (1980-1992) were retrospectively reviewed. There were 176 patients whereof 44 (25%) had polymicrobial bacteremia. The median age of patients was 75 years and 64.2% were 70 years or older. Of the patients 56.8% came from a nursing home, 64.2% had an indwelling Foley catheter, and 20.5% nosocomial bacteremia. The most common source of bacteremia was the urinary tract (52.8%) whereas the lower respiratory tract was an uncommon source. Hypotension was present in 30.1% of patients. The overall mortality rate was 29.0% with an attributable mortality rate of 25.6%. The mortality rate of polymicrobial bacteremia (38.6%) was higher than that of monomicrobial bacteremia (25.8%). For patients with monomicrobial bacteremia, significant increase in mortality was found in patients who had nosocomial infection (p < 0.02), whose source of bacteremia was other than the urinary tract (p < 0.01), who had ultimately fatal underlying conditions (p < 0.01), who had hypotension (p < 0.001), who had increase in serum creatinine (p < 0.05), or who had increase in serum bilirubin (p < 0.05). PMID- 7984965 TI - Cytomegalovirus disease of late onset following renal transplantation: a potentially fatal entity. AB - CMV disease (CMVD) is a recognized problem of the early post-transplant period (PTP) in renal transplant recipients. Information on CMVD in the late (> or = 2 years) PTP is scarce. We have observed 5 cases of CMVD during late (3-8 years) PTP during the last 15 years. Three of these patients died from CMVD. One of the patients with late-onset CMVD recovered spontaneously from mild pneumonitis, 1 patient with severe CMVD after therapy with ganciclovir/anti-CMV-IgG. CMVD was ascribed to primary infection in 4/5 patients, and transmission was attributed to blood products in 2 cases. At the time of CMVD, 4/5 patients were on stable immunosuppression with azathioprine/prednisone; 1 patient who died had received prednisone pulses 1 month prior to CMVD. Late onset CMVD is an underreported disease in renal transplant recipients, which warrants preventive measures and consideration of antiviral therapy. PMID- 7984966 TI - Screening for congenital cytomegalovirus infection among preterm infants born before the 34th gestational week in Finland. AB - 83 infants born before 34 weeks of gestation between 1989 and 1990 and cared for at a neonatal intensive care unit in Kuopio, Finland, were screened for congenital cytomegalovirus (CMV) infection, defined as a positive culture from the sample of urine taken on the first day after birth. Four infants were infected and excreted CMV in the urine. The overall incidence of CMV excretors was 4.8%. The incidence was 1/13 infants born before 28 weeks' gestation and 3/70 infants born between 28 and 34 weeks of gestation. The 4 CMV excretors were followed up for 12-25 months. Two children had normal psychomotor and mental development but exhibited decreasing head growth during follow-up. The other 2 developed severe psychomotor retardation, retinopathy of prematurity, chorioretinitis, and microcephaly. The long-term morbidity was associated not only with congenital CMV infection but to prematurity as well. The incidence of congenital CMV excretors in this preterm population seemed to be higher than reported previously among unselected live-born infants. Early diagnosis of congenital CMV infection would seem to be important in view of forthcoming new therapeutic regimes in the near future. PMID- 7984967 TI - Hemolysis and autoantibodies to triosephosphate isomerase in a patient with acute hepatitis A virus infection. AB - Having returned from a holiday in Southeast Europe, a 30-year-old German woman developed acute hepatitis. Hepatitis A virus (HAV) infection was diagnosed serologically. During the course of the infection, hemolysis was found. IgM antibodies against triosephosphate isomerase (IgM anti-TPI) were detected in the patient's serum from the acute phase of the HAV infection. Affinity purified IgM anti-TPI from the serum reduced the enzyme activity in vitro and caused an increased 51Cr release from erythrocytes. IgM anti-TPI is assumed to be one of the causative agents of hemolysis in HAV infection. PMID- 7984969 TI - Age specific prevalence of antibodies against Chlamydia pneumoniae in Iceland. AB - Chlamydia pneumoniae is a newly recognized common cause of respiratory tract infections. The aim of this study was to examine its prevalence in Iceland. The study was based on 1020 serum samples from individuals 0-99 years old. The samples were divided into 10-year age groups. IgG and IgM antibodies were determined with microimmunofluorescence assay. An IgG titer > or = 32 and IgM titer > or = 16 were considered positive. The prevalence of positive IgG titer in the study population was 53 +/- 16% (mean +/- SD, age group range 14-66%). Neither seasonal nor gender-based difference in IgG antibody prevalence was demonstrated. It was lowest in the youngest group, 0-9 years old (p < 0.001), but rose linearly to age 70 (p < 0.005). 34 samples were IgM positive on initial testing; most from the older age groups. 12 were rheumatoid factor positive as well. After treatment with caprine antihuman IgG antibodies all became negative. The prevalence of C. pneumoniae infections is high in Iceland according to these results and similar to that in neighbouring countries. The presence of IgM rheumatoid factor may cause false positive tests for pathogen-specific IgM by immune complex binding with pathogen-specific IgG, thereby requiring its removal before testing. PMID- 7984968 TI - Long-term histological outcome in patients with chronic hepatitis C treated repeatedly with interferon alpha-2b without sustained response. AB - Nine patients with chronic hepatitis C who responded with normal or near-normal serum alanine aminotransferase (s-ALT) levels during an initial interferon alpha 2b treatment course, but who had subsequent relapses with elevated s-ALT levels after treatment cessation, were retreated once (3 patients) or twice (6 patients). The liver histological findings before the first and after the last treatment course were compared. The mean follow-up time between the initial and the follow-up assessment was 44 months (range 34-53). The histological findings were classified as chronic persistent hepatitis (CPH), chronic active hepatitis (CAH) or cirrhosis (Ci) by using a numerical scoring system assessing each portal zone separately. In the initial biopsy, 2 patients were classified as having CPH and 7 as having CAH, 2 of whom with signs of cirrhosis. According to the conventional classification, 4/9 (44%) patients improved after treatment, 3/9 (33%) remained unchanged, and 2/9 (22%) deteriorated. The mean histological scores for the necro-inflammatory parameters: portal inflammation, piecemeal necrosis, spotty necrosis and fibrosis improved, but the changes did not reach statistical significance. We conclude that repeated interferon alpha-2b treatment courses are probably beneficial in patients with chronic hepatitis C who show a non-sustained response to interferon, since studies on the natural course of chronic hepatitis C have indicated a progressive deterioration of the histological picture in many untreated patients, most marked among those with CAH. PMID- 7984970 TI - Moraxella catarrhalis--an uncommon cause of community-acquired pneumonia in Swedish children. AB - In 284 Swedish children with community-acquired, roentgenologically verified pneumonia, antibodies to Moraxella (Branhamella) catarrhalis were determined in paired serum samples with an enzyme immunoassay using a whole-cell antigen preparation from 10 strains of M. catarrhalis. Only 9 children (3%) had significant increases in antibodies to M. catarrhalis. Among these 9 children, 11 39 months of age, 6 had serologic evidence of concurrent infection with other respiratory pathogens such as S. pneumoniae, non-capsulated H. influenza, RS virus and adenovirus. In 6 (67%) of the 9 children with antibody response and in 74 (27%) of the 275 children without antibody response to M. catarrhalis, nasopharyngeal cultures yielded growth of this bacterium. M. catarrhalis seems to be a common commensal in the upper respiratory tract, but a rare cause of pneumonia in children. PMID- 7984971 TI - Non-typhoid Salmonella meningitis. AB - The epidemiological, clinical and laboratory findings in 8 cases of meningitis due to non-typhoid salmonella were analyzed. Seven out of 8 patients were infants < 12 months old, 2 of whom died, 2 presented with recurrent meningitis. Three infants had reversible neurological sequelae on discharge, not found during follow-up in any. Conversely, one 2-month-old patient who was considered normal on discharge developed severe growth and mental retardation during follow-up. PMID- 7984972 TI - Cluster of multiresistant Escherichia coli O78:H10 in Greater Copenhagen. AB - A multiresistant, lactose-negative Escherichia coli O78:H10 was isolated from 19 patients in Greater Copenhagen over a period of 8 months. At least 14 cases were community-acquired. 18 isolates originated from urine cultures and 1 from a faecal sample. 13 patients were predisposed to urinary tract infection (UTI) and 11 patients showed clinical signs of UTI. This is the first report of E. coli O78:H10 causing human disease. The cluster was probably food-borne, but the source was not identified. This cluster of identical disease associated E. coli was only uncovered because of its multiresistance and lactose-negative phenotype. PMID- 7984973 TI - Polymicrobial and recurrent bacteremia with Shigella in a patient with AIDS. AB - Shigella gastroenteritis is uncommon among HIV seropositive patients and may be complicated in some patients by bacteremia; S. flexneri being the most frequently detected serogroup. While recurrent Salmonella bacteremia is common among HIV seropositive patients, recurrent Shigella bacteremia is not. We report here an HIV-seropositive patient with Shigella gastroenteritis, polymicrobial bacteremia due to S. flexneri and S. boydii, and recurrent gastroenteritis and bacteremia with S. boydii. Relapsing infection with the same strain of S. boydii was determined using pulsed field gel electrophoresis. Thus, HIV-seropositive patients who develop Shigella infections may require prolonged treatment and/or suppressive therapy, similar to those infected with Salmonella. Patients who develop recurrent disease should be suspected as having polymicrobial bacteremia since the incidence of this may be underestimated among patients with AIDS, particularly those with concurrent gastroenteritis. PMID- 7984974 TI - An outbreak of Legionnaires' disease in a Swedish hospital. AB - We report a nosocomial outbreak of Legionella pneumophila serogroup (sg) 1 infection at the general hospital, Varnamo, Sweden. From December 1990 to February 1991, 28 patients and 3 staff fell ill with pneumonia and 3 died. L. pneumophila sg 1 together with several other Legionellae were isolated from the hot water supply to 17 of 20 hospital wards, probably being spread by aerosolization via shower nozzles. Raising the hospital's hot water temperature from 45 degrees C to 65 degrees C, together with heat disinfection of the shower equipment, arrested the outbreak within a week. Keeping the hot water temperature > or = 60 degrees C without chlorination eliminated L. pneumophila from > 75% of the wards. During a period of 2 years after the outbreak we have diagnosed only 1 case of nosocomial legionellosis at the hospital despite an active surveillance program. PMID- 7984975 TI - Seroconversion for Lyme borreliosis among Dutch military. AB - Few prospective studies for Lyme borreliosis (LB) have been conducted among subjects at risk to acquire this disease during their work when wearing well defined protective clothing against tick-bites. We prospectively compared the rate of seroconversion and the occurrence of clinical manifestations of LB among 2 groups of Dutch military. The at risk-group worked predominantly outdoors, and the control-group conducted predominantly indoor activities. During outdoor work, the at risk-group wore long sleeves, long trousers, closed around the ankles and high boots. Initial serum samples from 2158 military were collected immediately after entering the service. From 932 military (at risk-group: 469, control-group: 463) a second sample was drawn 9 to 12 months later. Sera were tested for IgG and IgM antibodies by ELISA. Four persons (0.9%) in the at risk-group and 10 persons (2.2%) in the control-group seroconverted for IgG and/or IgM antibodies against B. burgdorferi. This difference was not statistically significant. Only 1 person who had seroconverted had noticed an erythema migrans. In conclusion, military performing outdoor activities have a low risk for infection with B. burgdorferi, most likely because they wear protective clothing. Among seroconverted persons clinical manifestations of Lyme borreliosis occurred rarely. PMID- 7984976 TI - Serum IgG antibody responses to Shigella invasion plasmid-coded antigens detected by immunoblot. AB - Serum IgG antibody responses to Shigella invasion plasmid-coded antigens (Ipa) from 58 Shigella flexneri, S. sonnei, and S. dysenteriae infected Swedish patients were investigated by immunoblot technique. Intense responses to most components of Ipa (Ipas A, B, C, D, and VirG-virulence determinant on SalI fragment G of the plasmid) were evident in sera from S. flexneri infected patients. The strongest response was to Ipa B and the weakest, to Ipa D. In contrast, there were weaker responses to Ipas A, B, C, and VirG but none at all to Ipa D in sera from S. sonnei infected patients. After absorption of the Ipa positive sera by Ipa expressing strains of S. flexneri and S. sonnei, most IgG antibodies to components of Ipa were removed in sera absorbed by S. flexneri, but IgG antibodies to Ipas--especially to Ipa D--were only slightly reduced in sera absorbed by S. sonnei, suggesting that Ipa D in S. sonnei may not be exposed on the S. sonnei cell surface. PMID- 7984977 TI - Clinical outcome of acute otitis media caused by pneumococci with decreased susceptibility to penicillin. AB - Raw data from 4 clinical studies involving pre-inclusion paracentesis were pooled to assess demographic characteristics and clinical outcome of acute otitis media (AOM) due to S. pneumoniae with decreased susceptibility to penicillin (SpRP). Children in the age range 3 months to 10 years were treated with beta-lactam antibiotics for 10 days. 54 children with SpRP AOM were compared with 182 children with penicillin-susceptible pneumococcal (SpSP) (AOM). The groups were found comparable with regard to sex, age at first AOM, and frequency of earlier bouts of AOM. SpRP AOM was significantly more frequent before age 18 months (40/54 versus 85/166 in the SpSP group; p = 0.003) and associated with more clinical failure on days 4-10 (10/54 versus 14/166; p = 0.03). These results suggest that the antibiotic treatment used to treat AOM in children under 18 months should be reconsidered in areas with a high incidence of SpRP. PMID- 7984978 TI - Effect of erythromycin treatment on antibody responses in pertussis. AB - The effect of erythromycin treatment on antibody responses to Bordetella pertussis filamentous haemagglutinin (FHA) and pertussis toxin (PT) was investigated in convalescent blood samples from 105 children with pertussis. Erythromycin had been given to 59 children, median age 3.2 years (range 0.3-9.9) on median day 7 (range 11-14) after onset of disease while the remaining 46 children, age 3.45 (0.6-8.1) were untreated. No significant differences in IgG antibody concentration were noted to FHA by ELISA and to PT, neither by NT nor by ELISA, but a tendency towards lower median titers was seen to both antigens and by both type of assays in the erythromycin-treated group. Similarly, early erythromycin treatment i.e. within 7 days of onset of symptoms, did not influence significantly of the development of the antibody responses but tended to lead to lower titer levels. A significant response to PT and FHA was found in about 90% of blood samples, irrespective of treatment. All 56 children with culture confirmed B. pertussis infection had a significant response to PT. The study has thus shown a slight but not significant effect of erythromycin treatment on antibody responses in pertussis. PMID- 7984979 TI - Immunity from diphtheria, tetanus, poliomyelitis, measles, mumps and rubella among adults in Lithuania. AB - Health authorities have estimated a low immunity level against diphtheria, tetanus, poliomyelitis, measles, mumps and rubella among adults in Lithuania due to less than optimal vaccine quality. The aim of this study was to evaluate the level of immunity by blood sampling 100 young women, 50 young men and 50 middle aged men and from the immunization history by questionnaire. Lack of protection against diphtheria was found in 0%, 2% and 46% of the young women, young men and middle-aged men respectively. The corresponding data for tetanus were 0%, 0% and 10%. It was found that 85% of the women had antibodies to all 3 types of polioviruses vs. 80% of the young men and 56% of the middle-aged men. A sub protective antibody level against measles was found in 12% of the women, 22% of the young men, but in none of the middle-aged men. A protective titre of rubella antibodies was found among 94% of the young, pregnant women. It can be concluded that the level of immunity in Lithuania is comparable to that in Western Europe for the same age groups and that the launching of adult vaccination programs in Eastern Europe should be preceded by sero-epidemiological studies. PMID- 7984980 TI - Seroconversion after additional vaccine doses to non-responders to three doses of intradermally or intramuscularly administered recombinant hepatitis B vaccine. AB - Hospital staff members who failed to respond (anti-HBs < 10 IU/l) after 3 doses of a recombinant hepatitis B (HBV) vaccine (given either as 20 micrograms intramuscularly (n = 8) or 2 micrograms intradermally (n = 15)) received 1 or 2 additional doses by the same route as the initial vaccination. After the first additional dose, 12/23 responded with anti-HBs levels > or = 10 IU/l and after the second, another 2/5 responded, corresponding to a total response rate of 61%. No significant difference was seen in the response rate according to vaccination route, gender, age, or whether the vaccinee was a smoker or not. In this limited study some 50% of non-responders to 3 intradermal or intramuscular doses of recombinant HBV vaccine seroconverted after an additional 1-2 doses given by the same route as the initial vaccination, suggesting that additional doses can be administered by the same route as the initial one. PMID- 7984981 TI - Immune status and booster effects of low doses of tetanus toxoid in Swedish medical personnel. AB - Of 102 medical staff at a Swedish hospital, 81% had tetanus antitoxin titres > or = 0.01 IU/ml in 1984-85. The unprotected individuals (antitoxin titre < 0.01 IU/ml) were all > 30 years of age. Of this group, one-third lacked a protective antibody level against tetanus toxin. Low booster doses of tetanus toxoid (0.75 or 1.9 Lf) were given to 66 vaccinees with a history of previous basic vaccination and no history of booster vaccination within the previous 5 years. The median titre increased from 0.26 IU/ml before to 3.3 IU/ml after vaccination. Low doses of tetanus toxoid may thus still provide an adequate immune response when given as a booster vaccination to individuals with a reliable history of basic immunization. PMID- 7984982 TI - Detection of Candida albicans DNA in serum by polymerase chain reaction. AB - Polymerase chain reaction (PCR) was applied in order to improve the diagnosis of disseminated candidosis. A nested PCR technique with 2 primer pairs was used to increase the sensitivity. We were able to detect Candida DNA in serum and tissue samples from experimentally infected mice as well as in serum samples from candidemia patients and patients with deep-seated Candida infection. Our PCR could detect as little as 1 pg Candida albicans DNA. The PCR method was more sensitive than culture in both the mouse experiments and the patients with deep candidosis (5/7 were PCR positive and 0/7 blood culture positive), and of similar sensitivity in candidemia patients (11/17 were 15/17 blood culture positive). The relatively short processing time of PCR, when compared with culturing, its sensitivity, as well as the possibility of using serum samples for analysis, all helped improve the diagnostics in deep-seated candidosis and candidemia. PMID- 7984983 TI - Encephalopathy associated with Salmonella enteritidis infection. AB - A 15-year-old boy who presented with a short history of a diarrhoeal illness associated with encephalopathic features is described. Salmonella enteritidis phage type 4 was cultured from his stool. Although encephalopathy in the absence of CNS infection or electrolyte disturbance is well described in enteric fever, it is very rare in infections with non-typhoidal Salmonella serotypes and has not previously been described in association with S. enteritidis infection. PMID- 7984984 TI - Salmonella paratyphi--an unusual cause of primary septic arthritis of the hip. AB - Salmonella paratyphi is an extremely rare cause of primary septic arthritis of the hip, especially in the U.K. The presentation is no different from other causative organisms. A case is described illustrating that uncommon organisms can cause septic arthritis and that for successful treatment correct organism identification is paramount. PMID- 7984985 TI - A case of haemorrhagic fever with renal syndrome complicated by spleen haemorrhage. AB - A case of haemorrhagic fever with renal syndrome (HFRS) complicated by spleen haemorrhage is described. The patient developed progressive anaemia, hypotension and signs of preshock. Computerized tomography demonstrated extensive haematoma in the spleen and splenectomy was performed. This case confirms previous reports that HFRS caused by Puumala virus may be associated with severe haemorrhagic manifestations. PMID- 7984986 TI - Mixed bacteremia with Vibrio metschnikovii in an 83-year-old female patient. AB - An 83-year-old woman suddenly fell ill and was admitted to the hospital on suspicion of a heart attack. After admission she developed high fever, chills and malaise. Vibrio metshnikovii and Staphylococcus hominis were isolated from 2 separately obtained blood cultures. One of the cultures also yielded Escherichia coli. The patient's condition improved rapidly after treatment with ampicillin intravenously. To our knowledge, this is the fourth reported case of V. metschnikovii bacteremia in humans. PMID- 7984987 TI - Bacteroides fragilis arthritis in a sickle cell-thalassaemia patient. AB - Anaerobic arthritis due to Bacteroides fragilis was diagnosed in a 33-year-old patient with prolonged fever suffering from sickle cell/thalassaemia. The causative agent was isolated from blood and purulent synovial fluid from both knee joints. A combination of chloramphenicol plus metronidazole treatment proved effective. Anaerobic arthritis has not previously been described in patients with sickle cell disease, and may reflect the well-known susceptibility of these patients to pathogens. PMID- 7984988 TI - Air crescent sign and fatal haemoptysis in pulmonary mucormycosis. AB - A case of invasive pulmonary mucormycosis complicated by fatal, massive haemoptysis in a patient with acute myeloid leukaemia is reported. This patient represents the twelfth reported case of fatal haemoptysis due to mucormycosis. The other 11 cases are reviewed and the aetiology of cavity formation and massive haemoptysis is discussed. The development of the air crescent sign on chest radiograph is an important clinical indicator of potentially fatal haemoptysis and should lead to appropriate antifungal and surgical therapy. PMID- 7984989 TI - [Questions about amalgam are at the center of attention]. PMID- 7984990 TI - [The modification of the metal ceramic bond by blended gold coating]. AB - The esthetic appearance of porcelain-fused-to-metal restorations is often compromised in areas in which the ceramic veneer has to be kept very thin. In order to overcome this esthetic problem, bonding gold products are offered by dental manufactures which act as an alloy seal, thereby improving the natural color appearance of the ceramic veneer. In addition, the bond strength between ceramic materials and alloys is said to be maintained or in some cases even increased. The present study investigated the effect of various types of bonding gold layers on strength of the bond between ceramic materials and numerous dental alloys as a function of the type of alloy used, using thermocycling over a period of two months with a total of 85,000 temperature changes. The analysis of the results obtained shows that, contrary to manufacturers' claims, only two of the eight bonding gold products can be recommended, and only for three of the twelve alloys tested, as far as the alleged added adhesion is concerned. Only very few combinations of alloys and bonding gold products did not adversely affect adhesion at all or only insignificantly. PMID- 7984991 TI - [Mercury concentrations in the urine of children with and without amalgam fillings]. AB - Studies on adults documented that most of the urinary concentration in occupationally non-exposed persons is determined by the number and extent of their amalgam fillings. Very few data concerning the mercury exposure of children are available. In this study the mercury concentration in the urine of 3-15-year old children with and without amalgam fillings was determined. The mean urinary mercury concentration for the children without amalgam (n = 93) was 0.17 microgram/l, and for the children with amalgam fillings (n = 86) it was 0.70 microgram/l. The creatinine adjusted values were 0.19 microgram/g and 0.64 microgram/g, respectively. This difference was significant (p < 0.001). Also, a significant correlation was found between the number of amalgam points (each amalgam surface had been given 1 to 3 points depending on its extent) and the urinary mercury concentration (r = 0.69). PMID- 7984993 TI - [Clinical and long-term scanning electron microscopic studies of composite inlays]. AB - 24 composite inlays, which were thoroughly documented for postgraduate education purposes were recalled after 13.3 and 30.5 months on average. The clinical evaluation yielded very good results after 13.3 and good results after 30.5 months, respectively. Marginal gaps were observed in 6.6% at the tooth-composite cement and in 27.1% at the composite cement-inlay-interface after 13.3 months using replica technique and SEM. There values were not significantly different from the findings at 30.5 months. The adhesive failures between inlay and composite cement were preferably located in large, multisurfaced restorations. No significant differences were found between direct immediate inlays and lab-made indirect inlays and between molar and premolar restorations, respectively. PMID- 7984992 TI - [Amalgam as the measure in filling therapy. A determination of its place]. AB - As the value of amalgam restorations is increasingly being questioned in modern dentistry, the clinical potential of amalgam restorations in general has been evaluated in this literature review. The major factors limiting the longevity of amalgam restorations are operator- and patient-related. Both factors will likewise influence the longevity of any new restorative concepts. Nevertheless, amalgam restorations remain the standard against which alternative materials are evaluated. Amalgam restorations are slowly loosing ground to the use of tooth colored materials, which are gaining in popularity. However, amalgam can not currently be withdrawn from the list of possible restorative materials used for patients in Switzerland. PMID- 7984994 TI - [Salivary gland diseases. Sialolithiasis in childhood--a report of 2 cases, the current diagnosis and therapy]. PMID- 7984995 TI - [Orthodontic treatment in the adult. The indications, treatment possibilities with and without oral surgery and the demands for and advantages of treatment]. PMID- 7984997 TI - [Periodontology--today and tomorrow. A report on the continuing dental education course in Flims from 2 to 8 October 1994]. PMID- 7984996 TI - [Amalgam under suspicion]. PMID- 7984998 TI - [Oral implantology--the procedures in dealing with different implant systems. A report on the fall seminar of the Swiss Society for Oral Implantology of 3 September 1994 in Zurich]. PMID- 7985000 TI - [The 1st National Congress for Dental Students. A report on the 1st National Congress of the Association for Dental Students of Switzerland on 30 April 1994 in Bern]. PMID- 7985001 TI - [A theoretical and practical introduction to logopedics. A report on the 2-day continuing education course for dentists and physicians on 25 and 26 August 1994 at the Logopedics School St. Gallen]. PMID- 7984999 TI - [Lightspeed--a new mechanical root canal preparation method. A report on 2 continuing education courses of the Clinic for Preventive Dentistry, Periodontology and Cariology, the Center for Dentistry, Oral Medicine and Orthodontics on 16, 17 and 18 June 1994 in Zurich]. PMID- 7985002 TI - [The Neuchatel Society of Dentists facing recession and economic difficulties. Interview by Catherine Strahm]. PMID- 7985003 TI - [About 1000 dentists attended a first. A report on the Annual Congress of the Societe Suisse de Parodontologie (SSP) and of the Societe Suisse de Prothese Dentaire (SSPD) on 15 to 17 September 1994 in Basel]. PMID- 7985004 TI - [The latest findings on bruxism, attrition and overdentures on implants. A report on the 22nd Congress of the Scandinavian Society for Prosthetic Dentistry (SSPD) from 25 to 27 August 1994 in Naadendal, Turku, Finland]. PMID- 7985005 TI - Insights into reproduction. PMID- 7985006 TI - Fighting antibiotic resistance. PMID- 7985007 TI - Imanishi-Kari case: ORI finds fraud. PMID- 7985008 TI - Breast cancer gene. Many mutations may make test difficult. PMID- 7985009 TI - Yale arbovirus team heads south. PMID- 7985010 TI - Large plots are next test for transgenic crop safety. PMID- 7985011 TI - Watching the brain remake itself. PMID- 7985012 TI - Obesity gene discovery may help solve weighty problem. PMID- 7985013 TI - Contraceptive methods go back to the basics. PMID- 7985014 TI - A booster for contraceptive vaccines. PMID- 7985015 TI - Stopping premature births before it's too late. PMID- 7985016 TI - Barriers hold back new contraception strategies. PMID- 7985017 TI - The two faces of hedgehog. PMID- 7985018 TI - Molecular basis of mammalian sexual determination: activation of Mullerian inhibiting substance gene expression by SRY. AB - The pathway of male sexual development in mammals is initiated by SRY, a gene on the short arm of the Y chromosome. Its expression in the differentiating gonadal ridge directs testicular morphogenesis, characterized by elaboration of Mullerian inhibiting substance (MIS) and testosterone. SRY and MIS each belong to conserved gene families that function in the control of growth and differentiation. Structural and biochemical studies of the DNA binding domain of SRY (the HMG box) revealed a protein-DNA interaction consisting of partial side chain intercalation into a widened minor groove. Functional studies of SRY in a cell line from embryonic gonadal ridge demonstrated activation of a gene-regulatory pathway leading to expression of MIS. SRY molecules containing mutations associated with human sex reversal have altered structural interactions with DNA and failed to induce transcription of MIS. PMID- 7985019 TI - The sex determination process in maize. AB - Maize partitions the sexes into different flowers on the plant, a condition called monoecy, which facilitates outcrossing. Sex determination in maize is a complex process involving an interplay between genetic determinants, the environment, and hormones. Unisexuality of flowers is achieved by the process of selective arrest and abortion of the inappropriate organ primordia within a bisexual floral meristem. Floral organ abortion is associated with the degeneration of cells within an immature primordia. Masculinizing genes are required for gynoecial abortion, feminizing genes arrest stamen development, and both types also control secondary sexual traits involving morphological characteristics of floral tissues. Gibberellins, steroid-like plant hormones, appear to play a pivotal role in the stamen abortion process and the feminization of floral tissues. PMID- 7985020 TI - Implantation and the placenta: key pieces of the development puzzle. AB - The mammalian embryo cannot develop without the placenta. Its specialized cells (trophoblast, endoderm, and extraembryonic mesoderm) form early in development. They attach the embryo to the uterus (implantation) and form vascular connections necessary for nutrient transport. In addition, the placenta redirects maternal endocrine, immune, and metabolic functions to the embryo's advantage. These complex activities are sensitive to disruption, as shown by the high incidence of early embryonic mortality and pregnancy diseases in humans, as well as the numerous peri-implantation lethal mutations in mice. Integration of molecular and developmental approaches has recently produced insights into the molecules that control these processes. PMID- 7985021 TI - Fertility decline in East Asia. AB - With the fall of fertility in China to near or below replacement levels in the early 1990s, the whole of East Asia may now be said to have completed a demographic transition. Its experience lies between that of the West and the many developing countries in which demographic transition is now under way. The main features and possible underlying causes of the fertility declines in Japan, Taiwan, South Korea, and China during this century are discussed. Fertility decline in East Asia is interesting both in its own right, as a chapter in the history of human reproduction, and for the light it may shed on fertility decline in the rest of the world. PMID- 7985022 TI - Insights from the study of animals lacking functional estrogen receptor. AB - Estrogen hormones produce physiological actions within a variety of target sites in the body and during development by activating a specific receptor protein. Hormone responsiveness for the estrogen receptor protein was investigated at different stages of development with the use of gene knockout techniques because no natural genetic mutants have been described. A mutant mouse line without a functional estrogen receptor was created and is being used to assess estrogen responsiveness. Both sexes of these mutant animals are infertile and show a variety of phenotypic changes, some of which are associated with the gonads, mammary glands, reproductive tracts, and skeletal tissues. PMID- 7985023 TI - Autoproteolysis in hedgehog protein biogenesis. AB - Extracellular signaling proteins encoded by the hedgehog (hh) multigene family are responsible for the patterning of a variety of embryonic structures in vertebrates and invertebrates. The Drosophila hh gene has now been shown to generate two predominant protein species that are derived by an internal autoproteolytic cleavage of a larger precursor. Mutations that reduced the efficiency of autoproteolysis in vitro diminished precursor cleavage in vivo and also impaired the signaling and patterning activities of the HH protein. The two HH protein species exhibited distinctive biochemical properties and tissue distribution, and these differences suggest a mechanism that could account for the long- and short-range signaling activities of HH in vivo. PMID- 7985024 TI - Scanning tunneling microscopy of insulators and biological specimens based on lateral conductivity of ultrathin water films. AB - Scanning tunneling microscopy is based on the flow of an electrical current and thus cannot be used to directly image insulating material. It has been found, however, that a very thin film of water (about one monolayer) adsorbed to a surface exhibits a surprisingly high conductivity that is sufficient to allow scanning tunneling microscope imaging at currents below 1 picoampere. Hydrophilic insulators, such as glass and mica, can thus be imaged in humid air. The same is true for biological specimens deposited on such surfaces, as demonstrated by the scanning tunneling microscope imaging of plasmid DNA on mica. PMID- 7985025 TI - Requirement for intron-encoded U22 small nucleolar RNA in 18S ribosomal RNA maturation. AB - The nucleoli of vertebrate cells contain a number of small RNAs that are generated by the processing of intron fragments of protein-coding gene transcripts. The host gene (UHG) for intro-encoded human U22 is unusual in that it specifies a polyadenylated but apparently noncoding RNA. Depletion of U22 from Xenopus oocytes by oligonucleotide-directed ribonuclease H targeting prevented the processing of 18S ribosomal RNA (rRNA) at both ends. The appearance of 18S rRNA was restored by injection of in vitro-synthesized U22 RNA. These results identify a cellular function for an intron-encoded small RNA. PMID- 7985026 TI - DNA bending by Cro protein in specific and nonspecific complexes: implications for protein site recognition and specificity. AB - Scanning force microscopy was used to resolve lambda Cro protein when bound as a single dimer or multiple dimers to its three operator (OR) sites. The bend angles induced by binding of Cro to specific and nonspecific sites were determined and are 69 degrees +/- 11 degrees for specific and 62 degrees +/- 23 degrees for nonspecific complexes. Bending of the nonspecific sites is advantageous for a protein such as Cro that bends its specific site, because it increases the binding specificity of the protein and it can be used by the protein to sample contacts required for the recognition of its target sequence. It is proposed here that bending of nonspecific DNA may be a general property among DNA binding proteins that bend their specific sites. PMID- 7985027 TI - Accumulation of HLA-DM, a regulator of antigen presentation, in MHC class II compartments. AB - The HLA-DM genes encode an unconventional HLA (human leukocyte antigen) class II molecule that is required for appropriate binding of peptide to classical HLA class II products. In the absence of DM, other class II molecules are unstable upon electrophoresis in sodium dodecyl sulfate and are largely associated with a nested set of peptides derived from the invariant chain called CLIP, for class II associated invariant chain peptides. DMA and DMB associated and accumulated in multilaminar, intracellular compartments with classical class II molecules, but were found infrequently, if at all, at the cell surface. Thus, DM may facilitate peptide binding to class II molecules within these intracellular compartments. PMID- 7985028 TI - Reconstitution of an operational MHC class II compartment in nonantigen presenting cells. AB - Professional antigen-presenting cells (APCs) have a distinct compartment in which class II molecules are proposed to acquire antigenic peptides. Genetic evidence suggests that human leukocyte antigen (HLA)-DM, an unusual class II molecule, participates in this process. Peptide acquisition was reconstituted in nonprofessional APCs by transfection of class II, invariant chain (li), and H-2M, the murine equivalent of DM. The H-2M heterodimer appeared in an endosomal compartment, not at the cell surface, and the localization was independent of li. The data presented show that H-2M, class II, and li are the minimally required components for efficient formation of stable class II-peptide complexes, and thus for a functional class II compartment. PMID- 7985029 TI - Reversion of the mouse pink-eyed unstable mutation induced by low doses of x rays. AB - Deletions and other genome rearrangements can be caused by radiation and are associated with carcinogenesis and inheritable diseases. The pink-eyed unstable (p(un)) mutation in the mouse is caused by a gene duplication and reverts to wild type by deletion of one copy. Reversion events in the mouse embryo were detected as black spots on the fur of the animals or microscopically as partially black hair in a background of colorless hair. The frequency of partially black hair was increased by x-rays at very low doses. A linear dose-response relation was found between 1 and 100 centigray. PMID- 7985030 TI - Exocytosis in spermatozoa in response to progesterone and zona pellucida. AB - Exocytosis in mammalian spermatozoa (the acrosome reaction) is a process essential for fertilization. Both progesterone and zona pellucida induce exocytosis in spermatozoa, which may encounter both during penetration of the oocyte's vestments. When mouse spermatozoa were exposed first to progesterone and then to zona pellucida, exocytosis was enhanced to a greater degree than that seen when the agonists were presented together or in the inverse order, which suggests that the steroid exerts a priming effect. Progesterone similarly primed the generation of intracellular messengers evoked by zona pellucida. The effects triggered by progesterone were mimicked by gamma-aminobutyric acid (GABA) and were blocked by bicuculline, which indicates that the steroid acts on a GABAA receptor. PMID- 7985031 TI - Mutant mice, Cu,Zn superoxide dismutase, and motor neuron degeneration. PMID- 7985032 TI - Survival of Chilean patients with systemic lupus erythematosus. AB - Environmental, genetic, and ethnic factors seem to be involved in the expression of systemic lupus erythematosus (SLE). It has been reported that SLE in the Spanish-heritage population is more common and severe than in the white population in the United States. Data on the population with SLE in South America are scarce, however. The survival of 218 Chilean patients with SLE was studied. General features of the disease were similar to those in most reports. Survival at 10 years was 79%. Prognostic factors (P < .01) were the clinical markers of renal severity, including clinical stratification of renal disease, SLE disease activity index, thrombocytopenia, thromboembolism, and the use of "megadose" corticosteroids. Multivariate analysis suggested that the disease activity index had the strongest association with outcome (P = .0007); thrombocytopenia added a marginal risk (P = .04). Renal histology was analyzed in 127 patients. Risk factors for survival were clinical renal stage, elevated serum creatinine levels, and high activity index. Chronicity index was not a risk factor. Survival curves for World Health Organization types II and III were better than for type IV (P = .06). Multivariate analysis showed that creatinine levels correlated inversely with outcome (P = .0363). Disease expression of Chilean patients with SLE was similar to that in most reports. Survival was somewhat lower than in developed countries, which may be attributable to socioeconomic and racial factors. PMID- 7985033 TI - Hypoprothrombinemia in childhood systemic lupus erythematosus. AB - Three children with systemic lupus erythematosus who developed hemorrhagic tendencies as a consequence of a clotting factor II (prothrombin) deficiency are described. All three responded rapidly to treatment with corticosteroids. A literature review added 25 case reports, with the following findings. First, factor II deficiency occurs in the presence of the lupus anticoagulant, although the interrelationship between the two is not understood. Second, the deficiency is presumed to be secondary to rapid clearing of the antigen/antibody factor II complex in the liver. Finally, most cases respond to corticosteroid therapy with or without the coadministration of vitamin K or fresh frozen plasma. In corticosteroid-dependent patients, the addition of antimetabolites such as azathioprine has enabled reduction in steroid doses. PMID- 7985034 TI - Twin studies in rheumatic diseases. AB - Twin studies attract both clinicians and geneticists because of the value of the twin method in helping unravel the genetic predisposition to diseases and the role of environment in their causation. In the field of rheumatology, there are many case reports on twins concordant or discordant for diseases. Interesting as such reports may be, very few generalizations can be made from them. The concordance rate among monozygotic (MZ) twins indicates the maximum level of genetic contribution. Based on studies of systematically compiled twin series, the concordance rate is about 15% for rheumatoid arthritis; the rate is probably of the same order of magnitude for systemic lupus erythematosus (SLE). The fine specificity of antinuclear antibodies of MZ twins at least one of whom is affected by SLE is very similar, despite somatic generation of immune diversity. Up to now, twin studies have provided little information on the role of environmental factors in rheumatic diseases. A notable exception is a case control study of MZ twins discordant for smoking that reinforced the role of smoking as a cause of lumbar intervertebral disc degeneration. PMID- 7985035 TI - Gastrointestinal manifestations of systemic sclerosis. AB - Gastrointestinal (GI) manifestations of systemic sclerosis (SSc) were found in 82% of 262 patients followed up prospectively. Esophageal dysmotility, lower esophageal sphincter laxity, bacterial overgrowth, and wide mouth diverticuli were the most common findings. The disease is usually diffuse with multiple levels of involvement. Gastrointestinal involvement was not significantly correlated with gender, age at SSc diagnosis or disease type (limited or diffuse scleroderma). Upper GI symptoms develop early in the course of SSc and may not correlate with objective findings. Various investigations, treatment regimens, and less frequent disease manifestations are reviewed and discussed. PMID- 7985036 TI - Serial nailfold capillary microscopy in primary Raynaud's phenomenon and scleroderma. AB - Eighty-four patients with long-standing Raynaud's phenomenon (RP) were evaluated by nailfold capillary microscopy (NCM) in a cross-sectional and longitudinal study. The patients were classified in five diagnostic groups: primary familial RP (n = 16), primary nonfamilial RP (n = 20), possible scleroderma (n = 27), scleroderma (n = 16), and the CREST (calcinosis, Raynaud's phenomenon, esophageal dysmotility, sclerodactyly, and telangiectasia) syndrome (n = 8). In the cross sectional study, NCM showed gradually decreasing numbers of capillary loops and increasing numbers of widened and giant loops in the following order: primary RP, possible scleroderma, and scleroderma/CREST, suggesting that these diseases are part of a continuing spectrum of RP. In the longitudinal study there was a decrease in the total number of nailfold capillary loops in scleroderma/CREST but not in primary RP and possible scleroderma. PMID- 7985037 TI - Leukemic arthritis. AB - Leukemic arthritis (LA) is an uncommon complication of both acute and chronic leukemias. LA occurs in 12% to 65% of childhood leukemia cases and 4% to 13% of adult leukemia cases. Involved joints usually are warm, swollen, and tender. This arthritis often is pauciarticular and preferentially involves large joints. LA occurs at any time during the course of leukemia and may be the presenting manifestation. Therefore, LA should be considered in the differential diagnosis of both adult and childhood rheumatic diseases. Establishing a diagnosis may be difficult and usually requires tissue biopsy. Newer immunochemical methods may help in the diagnosis of LA by demonstrating leukemic cells in synovial fluid. Therapy for the underlying leukemia is the treatment of choice. Decreasing joint pain often is the first sign of a clinical response to chemotherapy. A case report is presented and the literature on the subject is reviewed. PMID- 7985038 TI - Posterior interosseous nerve entrapment in rheumatoid arthritis. AB - Posterior interosseous nerve (PIN) entrapment is a rare complication of rheumatoid arthritis (RA) which, together with extensor tendon rupture and metacarpophangeal joint dislocation, should be considered in the differential diagnosis of inability to extend the fingers. The inability to extend the thumb in PIN entrapment is a useful distinguishing clue on physical examination, and nerve conduction studies confirm the diagnosis. Elbow joint swelling and compression of the PIN at the arcade of Frohse are the main reasons for PIN entrapment in RA. Intraarticular steroid injections and surgical intervention resolve symptoms of PIN entrapment in RA. In our case, the addition of methotrexate, which induces a rapid antiinflammatory effect, resulted in resolution of weakness with complete recovery in the extensor muscles of the fingers. PMID- 7985039 TI - Synovial cysts and ganglia: the value of magnetic resonance imaging. AB - Synovial and ganglion cysts commonly present in close proximity to joints and skeletal structures in rheumatic disorders. Familiarity with the presentation of these soft tissue masses can facilitate timely diagnosis and effective management, thus avoiding costly and potentially high-risk procedures to patients. Management usually consists of local, nonsurgical approaches. A patient with chronic joint deformities and clinical features primarily consistent with mixed connective tissue disease is described. Multiple localized masses developed at her right elbow and were identified on T2-weighted magnetic resonance imaging as multiloculated cysts that dissected from the elbow joint. The cysts were treated successfully by needle aspiration and intraarticular corticosteroid injection. The clinical associations, diagnosis, treatment, and management of synovial cysts and ganglions are reviewed. PMID- 7985040 TI - Disorders of the central nervous system. AB - In this article, we have reviewed the most common CNS abnormalities seen in perinatal medicine. The prognosis in ventriculomegaly is most closely related to the presence or absence of associated anomalies. The current treatment for DWM consists of shunting of either the posterior fossa cyst or lateral ventricles. Facial abnormalities can frequently aid in distinguishing holoprosencephaly from other CNS lesions. Anencephaly is one of the most severe fetal anomalies and is incompatible with life. Spina bifida represents a spectrum of NTDs with a variable outcome depending on the size and location of the defect, as well as the presence of other anomalies. PMID- 7985041 TI - Diagnosis and management of skeletal dysplasias. AB - The prenatal diagnosis of skeletal dysplasias is a challenging task due to the varied manifestations of the disorders and the great number of possible diagnoses. This difficulty will likely remain until DNA mutations are identified that will permit a specific diagnosis. Until then, the use of a multidisciplinary team is suggested for clinical diagnosis and management. Use of a systematic approach to diagnosis such as our "10-step" system is a valuable tool to decrease the complexity of the diagnostic process. Even if it does not lead to a specific diagnosis, it allows one to predict the likelihood of a severe or lethal disorder. A cautious approach to prenatal diagnosis of skeletal dysplasias is warranted due to the uncertainties inherent in clinical diagnosis of these disorders. Until specific DNA testing or rapid collagen analysis are available for the more common defects, errors in diagnosis and counseling that follow may result in termination of normal fetuses and, conversely, in continuation of pregnancies with lethal anomalies or severely affected fetuses. PMID- 7985042 TI - The role of ultrasound in the diagnosis and management of intrauterine growth retardation. AB - Ultrasonography has contributed greatly to our ability to diagnose and evaluate fetuses with IUGR. This tool has helped us begin to understand the pathophysiology of the spectrum of disorders we group as growth restriction. The heterogeneity of the syndrome contributes to our inability to find perfect sonographic diagnostic markers, but the information gained from ultrasound still far surpasses that available from other clinical methods. Sonographic estimated fetal weight seems to be the best parameter for diagnosing IUGR, although weight percentiles alone will lead to misdiagnosis or missed diagnosis in some cases. Umbilical artery velocimetry may be the best diagnostic tool in cases in which gestational age is unclear, but sensitivities are not adequate for general screening. Growth measured by change in abdominal circumference also shows promise for diagnosis of IUGR, but is dependent on serial examination. Doppler velocimetry has provided insight into the hemodynamic changes which occur with growth restriction, but findings are poorly predictive of outcome when used for screening. When end diastolic flow is absent or reversed, the incidence of adverse outcome can be high, but adverse outcome can occur without these findings and normal outcomes can occur despite them. The search for methods to improve assessment of fetal status and manage pregnancies with IUGR to maximize fetal outcome will continue. PMID- 7985043 TI - Management strategies for infectious diseases in pregnancy. AB - This review presented the clinical manifestations, diagnostic and therapeutic options, and preventive strategies for several congenital infections. The infections discussed show the spectrum of modes of vertical transmission and severity of fetal disease encountered, in addition to the successes and limitations of the current medical interventions. Further improvements in diagnostic techniques and therapies for managing the infected fetus are likely to occur during the next decade. Similarly, the widespread adaptation of new and sensitive diagnostic assays, such as the polymerase chain reaction, is likely to further improve our ability to identify infectious agents as the primary cause of certain abnormal fetal conditions. Where specific diagnostic tests and therapies have proven successful in preventing or treating fetal infections, universal screening programs should be given serious consideration. Of paramount importance, however, is the active research on the development of preventive interventions designed to prevent maternal infections and vertical transmission. Although specific immunotherapies, vaccines, and drug therapies hold great promise for controlling the spread of some infections, it cannot be overemphasized that some serious infectious complications of pregnancy may be avoided by simple preconception or early antenatal maternal counseling. PMID- 7985044 TI - Nonimmune hydrops fetalis. AB - In summary, NIHF is a heterogenous disorder resulting from a vast number of underlying pathologies. A thorough evaluation should be performed in all cases to attempt to establish the etiology. This requires a systematic approach that should logically proceed from least to most invasive testing. Despite increasing availability of treatment for some causes of NIHF, the prognosis for this condition in general remains poor. In cases of fetal or neonatal demise, autopsy should be encouraged to aid in confirming or making a diagnosis. It is especially important to rule out potentially treatable conditions, as well as genetic disorders with a risk of recurrence in future pregnancies. PMID- 7985045 TI - Rhesus sensitization and alloimmune thrombocytopenia. AB - Significant progress has unquestionably occurred in the diagnosis and treatment of fetal and neonatal alloimmune thrombocytopenia. However, fundamental aspects of this disease are still not fully understood, especially those factors that account for the diverse clinical spectrum of this disease. This impacts our ability to counsel patients regarding the ultimate outcome of fetuses affected with AIT. IVIG appears to be a promising treatment for fetuses affected with this disease. In all likelihood, fetuses affected with AIT are at higher risk for serious bleeding complications related to fetal blood sampling procedures, but this risk remains to be further defined. PMID- 7985046 TI - Prenatal diagnosis and management of fetal tumors. PMID- 7985047 TI - Prenatal genetic diagnosis by isolation and analysis of fetal cells circulating in maternal blood. AB - In recent years, considerable progress has been achieved in the genetic analysis of fetal cells isolated from maternal blood. The goal of clinical diagnosis of either fetal chromosome abnormality or Mendelian DNA mutation has already been realized in an ever-increasing number of cases. The remaining challenges involve increasing the yield and visual identification of fetal cells while decreasing the remaining numbers of maternal cells. It is presently unknown whether the frequency of fetal cells in maternal blood differs in cytogenetically abnormal pregnancies as compared with normal pregnancies. Although fetal cells in maternal blood have a practical role in prenatal diagnosis, their very existence and persistence in the mother raise many new questions regarding maternal-fetal interaction. PMID- 7985048 TI - In utero hematopoietic stem cell transplantation and gene therapy. PMID- 7985049 TI - Invasive fetal therapy: current status and future directions. PMID- 7985050 TI - [Oral anticoagulation today: between Scylla and Charybdis]. PMID- 7985051 TI - [Effect of treatment with 13-cis-retinoic acid and ara-C on the hematopoietic stem cells of patients with myelodysplastic syndromes]. AB - PURPOSE: To assess the "in vivo" effect of 13-cis-retinoic acid and low dose Ara C in MDS as well as to establish "in vitro" advantage of retinoid dose-related growth pattern on bone marrow cultures as defined by culture timing and CFU-GM proliferative response. PATIENTS AND METHODS: We evaluated 28 patients diagnosed of MDS according to FAB classification, of whom 4 cases had RA, 8 cases SRA, 14 cases RAEB and 2 cases RAEB-T. Patients who had RA and SRA were treated with oral 13-cis-retinoic acid at doses of 20-40 mg daily for 4 months and those cases with RAEB and RAEB-T had subcutaneous Ara-C at doses of 3 mg/m2 twice a day for 21 days. The "in vivo" and "in vitro" effect of retinoic acid on the haemopoietic differentiation was evaluated by the growth CFU-GM in semisolid cell culture methods. RESULTS: Increasing in vitro concentrations of 13-cis retinoic acid did not enhance the growth of myelodysplastic progenitors. Nevertheless, our study did not find any beneficial therapeutic effect of retinoic compounds in MDS patients. In this study, low-dose Ara-C (3 mg/m2) showed similar effects when compared with higher doses reported by others. Furthermore, in terms of CFU-GM proliferation the concentration of colonies before and after treatment were fairly similar in all but two patients. CONCLUSIONS: The results drawn from our study demonstrated that there is no beneficial advantage of 13-cis-retinoic acid as a differentiation inducing agent on myelodysplastic patients. In contrast, lower doses of Ara-C showed similar effects on haemopoiesis of MDS patients than standard doses of 10-20 mg/m2 but with less side effects. PMID- 7985052 TI - [Comparative multicenter study of a rabbit high-sensitivity thromboplastin and a recombinant thromboplastin with synthetic phospholipids]. AB - PURPOSE: The purpose of the present study was to compare the results obtained with a human recombinant thromboplastin (Innovin, Baxter) (IN) and a high sensitivity rabbit brain reagent (Thromboplastin IS, Baxter) (IS), on the performance of prothrombin time (PT) test and the functional assay of factors included in the extrinsic coagulation system, in order to establish possible differences on imprecision, diagnostic accuracy and sensitivity to the oral anticoagulant defect, between the two products. MATERIAL AND METHODS: Six Spanish hospital took part in the study. Plasma samples from 221 healthy subjects, 100 patients with severe liver disease, 27 with dysfibrinogenaemia, 10 with lupus anticoagulant and from 13 individuals propositus and their relatives with congenital deficiencies of the extrinsic coagulation pathway, and their relatives were studied; 188 patients stabilized on oral anticoagulant therapy and 82 on heparin therapy were also included. The in vitro effect of heparin was tested by addition of increasing amounts of heparin (0.3 to 10.0 IU/mL) to aliquots of normal plasma. RESULTS: Both in the intra-assay and in the inter-assay imprecision study, a better coefficient of variation was obtained with IN when the PT was performed on abnormal samples. Prothrombin time ratio from patients with liver disease had significantly higher values with IS. On the contrary, IN had a higher sensitivity in samples from patients with dysfibrinogenaemia or from those stabilized on oral anticoagulant therapy. In showed a very low sensitivity to heparin at concentrations corresponding to the therapeutic range. CONCLUSIONS: The results of this field study indicate that IN, compared with a high sensitivity rabbit brain thromboplastin, is a suitable reagent for PT determination in normal subjects, patients with liver disease or with congenital deficiencies of clotting factors. It shows a higher sensitivity in cases of dysfibrinogenaemia and in patients on oral anticoagulant therapy. In addition, the recombinant reagent had better reproducibility when the PT was performed on abnormal samples, and it was hardly affected by heparin within the therapeutic range. PMID- 7985053 TI - [Frequency of molecular alterations in heterozygous beta-thalassemia in southern Spain and their relation to the hematologic phenotype]. AB - INTRODUCTION: Heterozygous beta-thalassemia manifests hematologically with microcytosis, reduced red blood cell hemoglobin concentration and high hemoglobin A2 levels. Almost all molecular alterations are due to point mutations. We attempt to determinate the frequency of that mutations in the Oriental Andalusia Area, and its relationship with the hematological phenotype. PATIENTS AND METHODS: We have studied 45 heterozygous patients. DNA samples were amplified by PCR, using the printers CD7 and HI1. A 16 Kb fragment corresponding to beta globin gene was obtained and analyzed by Dot Blot assay and hybridized with allelic specific oligonucleotide (ASO) probes to detect the 6 more frequent mutations found in the South of Spain. RESULTS: Codon 39 nonsense mutation (31.1%) was the most frequent finding followed by IVS-1 NT 110 (26.7%). The relationship between hematological parameters and molecular mutations concluded that IVS-I NT 6 mutation developed a minimal anemia. DISCUSSION: From the practical point of view, this study indicates that we were able to detect more than 90% of heterozygous beta-tal. with 5 out of 6 ASO probes used in this work. Thus, our data also provides a further implication in prenatal diagnosis. PMID- 7985054 TI - [Checking oral anticoagulation in capillary blood]. AB - PURPOSE: To check out the reproducibility and costs of prothrombin time (PT) determination as a control of oral anticoagulant therapy (OAT) in plasma and capillary blood. PATIENTS AND METHODS: The study was carried out in two phases: along two years, 1,700 patients with OAT were controlled, 700 of them in the hospital outpatient clinic. In 149 patients INR was simultaneously determined in both capillary and venous blood. The 700 patients receiving acenocoumarin who had been controlled in 1991 according to the conventional plasma-sample fashion, were controlled in the second year (i.e., 1992) by means of capillary blood testing, a comparison of the costs of each method and the need for anticoagulant drugs being undertaken. Venous blood PT was assessed with reagent thromboplastin (Tromborel S) in an Electra-1000 (MLA) system. An automated Trombotrack system was used for the capillary blood tests using Thrombotest as current procedure. The results were expressed as INR in both methods. The statistical evaluation of the results was carried out by means of Student's t, variance analysis, and correlation study. RESULTS: No significant differences were found in the anticoagulation intervals attained from venous or capillary blood samples. No significant differences were seen in 87 patients on whom the test was repeated in two samples drawn from a single capillary puncture. The weekly OAT doses of 30 patients along six months were analysed. The need for anticoagulant drugs was similar (17.4 vs 17.2 mg/patient/week). The mean INR in 1991 was 2.82 and the mean drug-need was 15.24 mg/week, whereas in 1992 the mean INR was 2.86 and the need for anticoagulant was 15.49 mg/week. The costs of the conventional method were 103.6 Pta, this being 70 Pta for capillary blood, which means a 32% savings. CONCLUSIONS: OAT control by means of PT performed on capillary blood must be considered a substitutive method for the venous blood assay due to its efficacy, simplicity and lower costs. PMID- 7985056 TI - [Epidemiology of non-Hodgkin's lymphomas]. PMID- 7985055 TI - [Functional characterization of a monoclonal antibody which interferes with the binding of t-PA to fibrin]. AB - PURPOSE: Development of monoclonal antibodies capable of inhibiting the specific binding of t-PA to fibrin. MATERIAL AND METHODS: After immunization of Balb/c mice with recombinant t-PA (rt-PA) we selected the monoclonal antibody MA3B5 by its ability to inhibit the binding of t-PA to fibrin, and the MA2C1 devoid of this property. The influence of such antibodies was evaluated on fibrin plates, amidolytic assays and clot lysis assays. Furthermore, their interference with the activator bound to fibrin was assayed with a spectrophotometric solid phase assay (SOFIA). RESULTS: The results showed that MA3B5 totally inhibited the t-PA induced fibrinolytic activity on fibrin plates, reduced amidolytic activity by 86.5% and inhibited the clot lysis induced by t-PA in a dynamic system. In contrast, the MA2C1 showed no inhibition. By assessing the binding of t-PA to fibrin with the SOFIA assay we could demonstrate that only the MA3B5 reduced significantly (up to 90% with 100 micrograms/mL of antibody) the amount of t-PA bound to fibrin surface. CONCLUSION: We have purified and characterized a monoclonal antibody which specifically blocks the fibrin binding site of t-PA. PMID- 7985057 TI - [Phenotypic characterization of normal myeloid differentiation]. PMID- 7985058 TI - [Familial thrombophilia due to resistance to activated protein C]. AB - Resistance to activated protein C (RAPC) has been described recently as a cause of trombophilia; this may justify up to 50% of thromboembolic disease without predisposing cause in patients under 45 years. A 29 years-old male with a previous deep venous thrombosis (DVT) in the lower left limb three years earlier, developed a DVT in the right lower limb after a trauma of the knee that required immobilization, was associated to pulmonary thromboembolism diagnosed by gammagraphic methods. The phlebographic study showed femoro-iliaco-caval venous thrombosis. The proband's father and a younger brother had a previous history of thrombotic episodes. The following tests, were performed in the proband and relatives: prothrombin time, aPTT, thrombin time, fibrinogen, (Von Clauss), antithrombin III (chromogenic), protein C and protein S (coagulometry and ELISA), plasminogen (chromogenic) and lupus anticoagulant (ITT, dRVVT, aCL). RAPC was evaluated in two different samples. The proband study was performed under oral anticoagulation treatment (OAT). Control groups were: 21 blood donors and 12 OAT patients. The results showed a decreased response to APC in the proband (ratio 1.5) and relatives: father (1.4), brothers (1.5 and 1.5), while the mother was within the normal range (> or = 2). In normal controls and OAT patients the ratio was over 2. No other abnormalities were detected in the assays performed. It is concluded that RAPC is the cause of this familial trombophilia. RAPC should be included in the evaluation study of trombophilia. PMID- 7985059 TI - [Gray-platelet syndrome associated with Marfan disease in a Mexican family]. AB - Grey-platelet syndrome is a rare familial platelet impairment characterised by lack of alpha granules and giant vacuolated platelets. A Mexican family with grey platelet syndrome associated to Marfan disease is presented. The family was comprised of 22 members, of whom 3 (the propositus and two of his nephews) could be studied. Two of them, with haemorrhagic symptoms since childhood, had moderate prolongation of the Ivy bleeding time which improved after DDAVP administration, plus moderate thrombocytopenia, giant platelets and abnormal platelet aggregation induced by adrenalin, ADP and collagen. Platelet factor 4 was normal. Electron microscope examination of platelets showed lack of alpha granules and increased dense bodies. The rarity of the casual association of two low-frequency genetic diseases, namely Marfan disease and the grey-platelet syndrome, is commented, along with the response attained with DDAVP in the two affected individuals. PMID- 7985060 TI - [Acute thoracic syndrome]. AB - The acute chest syndrome is a clinical entity appearing in patients suffering from sickle cell anaemia. It presents with pleuritic pain, fever, leucocytosis and pulmonary infiltrates in the thoracic radiology. The etiological diagnosis is difficult, and it is necessary to distinguish between pneumonia and pulmonary infarction. This syndrome is quite frequent among the patients at risk, and can be lethal according to the severity and the etiology of the event. A case of acute chest syndrome due to a S. pneumoniae sepsis is presented. The interest of the case lies in the rareness of this disease in our population and the peculiar evolutive clinical features of this case, with the development of intracranial hypertension and death. PMID- 7985061 TI - r-huEPO in MDS: the day after. PMID- 7985062 TI - [Familial autoimmune thrombocytopenic purpura]. PMID- 7985063 TI - [Chronic myeloid leukemia in a 65-year-old man with early appearance of an intermediate-phenotype extramedullary blast crisis]. PMID- 7985064 TI - Hemorrhoids, fissures, and pruritus ani. AB - The diagnosis and management of hemorrhoids, fissures, and pruritus ani probably accounts for more than 81% of the complaints centered on this part of the human anatomy. This brief treatise offers a safe and practical approach to the management of these three diseases. PMID- 7985065 TI - Anorectal abscess-fistulae. AB - Anal abscess-fistulae have a tendency to recur based on variations in anatomic configuration and complexities of operative treatment and problematic postoperative healing. A classification of superficial, simple, complex, and recurrent fistulae was used to track outcome. Recurrence rates are substantially higher for those fistulae classified as complex. The reasons for this are discussed in this article. PMID- 7985066 TI - Pilonidal disease. AB - It is the author's preference and recommendation that an acutely infected pilonidal abscess be urgently drained with a simple incision and drainage procedure that is not necessarily viewed as definitive treatment. The patient should be so instructed. The definitive treatment of chronic pilonidal disease can be accomplished in a variety of ways, but our recommendation is excision of all infected tissue and sinus tracts through an elliptical incision with either marsupialization of the wound or beveling of the skin edges. Both marsupialization and beveling serve to minimize the chance of premature skin closure and promote complete healing of the site from the inside out. Weekly postoperative follow-up is strongly encouraged to assess progress and promote proper wound healing. PMID- 7985067 TI - Perianal hidradenitis suppurativa. AB - The management of hidradenitis suppurativa is individualized according to the site and extent of the disease. Initially, short-term antibiotics, local care, and incision and drainage are helpful. Unroofing of sinus tracks, total disease excision, and vigorous physical therapy are more beneficial. Primary or secondary closure or closure by an advancement flap or selective split-thickness skin grafting should be considered in some refractory cases. In most areas, recurrence rates are high unless wide excisions are performed, but perianal hidradenitis can usually be managed more conservatively. Patients with intra-anal disease are better allowed to heal secondarily than by grafting. Split-thickness grafts may contract and lead to anal stenosis, and grafts that are rejected may lead to deep scarring and anal dysfunction. The perianal region is best treated by local excision with secondary closure or by unroofing and curettage when the perianal region is more extensively involved. PMID- 7985068 TI - Perianal condylomata acuminata. AB - Perianal condylomata, a result of clinical infection with human papillomavirus, are an increasing problem. The warts lead to bleeding, itching, and discomfort in the anal region and also may be associated with anal canal neoplasia. Treatment options are numerous and include chemical caustic agents, surgical ablative methods, and immunotherapy. A high rate of recurrence is encountered despite the best of efforts. PMID- 7985069 TI - Fournier's gangrene. AB - Fournier's gangrene is the result of a highly lethal and rapidly progressive necrotizing infection of the perineal and genital fascia, with gangrene of the overlying skin. The infection is generally polymicrobial and probably synergistic in nature. Anorectal, genitourinary, and traumatic infections are the most common causes of Fournier's gangrene. The cutaneous manifestations of Fournier's gangrene are merely "the tip of the iceberg" because the infection spreads aggressively along recognized fascial planes. Perioperative fluid resuscitation, cardiopulmonary support, antibiotic therapy, and nutritional support are of major importance in management of the disease; however, examination under anesthesia with aggressive surgical debridement remains the most important aspect of treatment. Multiple surgical procedures may be necessary to bring the infection under control. In the majority of instances, the testes, glans penis, bladder, and rectum are spared destruction because of their separate blood supplies. Diversion of the fecal and urinary streams may not always be necessary but should always be considered on a case-by-case basis. The value of hyperbaric oxygenation in Fournier's gangrene remains unproven, but there are theoretical reasons why it may be beneficial, at least in some cases. Despite optimal medical and surgical management, the mortality rate in Fournier's gangrene still exceeds 40% in many series. PMID- 7985070 TI - Anal stenosis. AB - Anal stenosis is an abnormally tight inelastic anal opening that resists digital examination and is most commonly the result of excessive scarring following anorectal surgery. Surgical correction consists of excision of scar tissue, judicious internal sphincterotomy, and replacement of tissue with healthy skin or mucosa. The author's preferred procedure of advancement mucosal anoplasty is described in detail. PMID- 7985071 TI - Anovaginal fistulae. AB - Anovaginal fistulae are an uncommon type of anal fistulous disease. The symptoms can be minimal but frequently are disabling. Obstetric injury is the most common cause, but many other disease states can produce this communication. It is important to completely evaluate the patient before any consideration is given to surgical correction. This includes evaluation of the function of the anal sphincter, involvement of any other organ systems, and tissue diagnosis if the cause is uncertain. It is also important to delay surgical correction until any inflammation and infection have subsided. Many different surgical procedures have been reported in the literature for repair of these fistulae, most with success rates of at least 75%. It is important to remember the physiologic high-pressure zone in the anal canal when planning surgical correction. Fistulae secondary to inflammatory bowel disease have a markedly reduced success rate, and the presence of anal Crohn's disease should be suspected, especially when a previous surgical repair has failed. Medical management should be used either to heal the fistula nonoperatively or to improve the surgical result. Finally, some fistulae secondary to neoplasia, radiation, anastomotic leaks, or inflammatory bowel disease require diversion of the fecal stream either as an adjunct to repair or as definitive treatment. Proper preoperative evaluation of the patient and selection of the operation provide the optimum result. PMID- 7985072 TI - Fecal incontinence. AB - Fecal incontinence is a common but infrequently reported, imperfectly understood, multifactorial disease with far-reaching socioeconomic and psychological implications. Limited success with somewhat empirical surgical procedures implies that patients should be investigated fully, indications for surgery should be clear, and disability should be serious enough to demand surgical intervention. Dietary adjustments and medical treatment should be tried first. Unwelcome though it is, colostomy may be the ultimate remedy in some patients. PMID- 7985073 TI - Pelvic floor disorders. AB - The pelvic floor conditions form a diverse array of primarily functional conditions that are rarely life-threatening but may be severely debilitating. Reassurance combined with initial medical and dietary management of most of these conditions greatly ameliorates the suffering of most patients. Surgical intervention is most successful in patients with demonstrable defects such as mechanical sphincter disruption or obvious complete rectal prolapse. Surgery should be offered only to patients with other functional pelvic floor disorders who manifest intractable symptoms. PMID- 7985074 TI - Lasers in anorectal surgery. AB - Laser technology has been applied widely in the treatment of hemorrhoids, condylomas, and anorectal neoplasms. It is claimed by its proponents to result in less pain, improved healing, and more rapid recovery as compared with conventional surgery. Laser therapy, however, is expensive and potentially dangerous, and advantages generally have not been substantiated by controlled clinical trials. The possible benefits and potential risks of laser treatment of anorectal disorders are examined. PMID- 7985075 TI - Sexually transmitted diseases and anal manifestations of AIDS. AB - During the past 20 years, there has been an increased use of the anorectum for erotic pleasure. Consequently, this has led to an overwhelming rise in sexually transmitted diseases (STDs) of the anus and rectum. It is important that surgeons involved with the care of colon and rectal disorders be familiar with each of these diseases. The recent AIDS epidemic has been a challenge to the medical community. Equally as challenging is the management of common anorectal disorders in the AIDS patient. AIDS not only influences the manner in which STDs present but is associated with its own spectrum of anorectal disorders. Discussion and management of STDs and anorectal disorders of AIDS patients are presented. PMID- 7985076 TI - Intrarectal and intra-anal ultrasonography in the evaluation of colorectal pathology. AB - Recent advances in ultrasonography have improved significantly the accuracy and applicability of this technology to the management of anorectal pathology. Intrarectal ultrasonography has demonstrated a high degree of accuracy in the assessment of extent of local invasion of rectal carcinomas as well as the degree of regional lymph adenopathy. It also is capable of playing a significant role in the management of anorectal suppurative disorders by allowing identification of deep-seeded abscesses. This technology will play an expanding role in the management of anorectal disorders and should be in the armamentarium of the surgeon managing these problems. PMID- 7985077 TI - Neoplasms of the anus. AB - Anal cancers can be grouped into three major categories. First, anal margin lesions are usually well-differentiated, keratinized squamous cell carcinomas that are amenable to local treatment measures. Second, anal canal cancers distal to the dentate line are mostly epidermoid, nonkeratinizing, moderately differentiated tumors. They are usually best treated with a multimodality approach using chemoradiotherapy and reserving surgery for clinical failures. Third, cancers arising in the ATZ are usually adenocarcinomas, and their treatment depends upon local factors. APR is in order for locally aggressive lesions, but newer protocols are studying multimodality therapy for this entity as well. Other, less common cancers of this region should be evaluated based upon their biologic potential and local involvement, with treatments selected accordingly. PMID- 7985078 TI - Anorectal trauma and foreign bodies. AB - The causes of rectal trauma are many and varied. The most frequent cause is iatrogenic. Treatment depends on the severity of the injury; and the accurate assessment of the injury is essential. Rectal foreign bodies are either ingested or inserted through the anus. Foreign bodies usually can be extracted by nonsurgical methods but appropriate technique is required to avoid rectal or sphincteric laceration. PMID- 7985079 TI - Fine-needle aspiration of normal thyroid tissue may result in the misdiagnosis of microfollicular lesions. AB - BACKGROUND: Inadvertent sampling of normal thyroid tissue surrounding a nodule may occur when clinically inexperienced personnel perform fine-needle aspiration (FNA) or when a nodule is small. Because the cytologic characteristics of normal thyroid tissue are not well known, we prospectively studied 42 patients undergoing thyroidectomy. METHODS: FNA was performed from the grossly normal contralateral lobe during thyroidectomy. Cytopathologists examined the slides without knowing the source of the tissue. RESULTS: FNA of grossly normal thyroid tissue was adequate for interpretation in 32 of 42 patients, and in nine of 42 cases it was interpreted as unremarkable. However, the remaining specimens were classified as microfollicular lesions (18), mixed macromicrofollicular lesions (three), Hurthle cell lesion (one), and papillary thyroid carcinoma (one). CONCLUSIONS: FNA of grossly normal thyroid tissue suggested a microfollicular lesion in 18 (56%) patients, a result that would raise the possibility of a follicular carcinoma and often lead to the recommendation for operation. When FNA is performed, normal thyroid tissue surrounding a nodule should be avoided, and the possibility of a sampling error should be considered when a microfollicular pattern is obtained in a patient with a small nodule. PMID- 7985080 TI - N-ras mutation: an independent prognostic factor for aggressiveness of papillary thyroid carcinoma. AB - BACKGROUND: The clinical importance of point mutations of ras oncogene in differentiated thyroid cancers has not been fully clarified. The purpose of this study is to determine the prognostic importance of ras mutation in papillary thyroid carcinoma. METHODS: Tumors of 91 patients with papillary carcinoma were studied; mean follow-up was 14.1 years (range, 1 to 40 years). Patients were grouped as follows: class I, intrathyroidal disease, n = 21; class II, cervical node metastases, n = 22; class III, extrathyroidal disease, n = 19; and class IV, distant metastases, n = 29. DNA was analyzed with polymerase chain reaction, oligonucleotide hybridization, and DNA sequence analysis techniques. RESULTS: Thirteen (14.3%) of 91 tumors showed an N-ras point mutation: 4.8% (1 of 21) patients in class I; 4.5% (1 of 22) patients in class II; 15.8% (3 of 19) patients in class III; and 27.8% (8 of 29) patients in class IV. Each mutation changed codon 61 from glutamine to arginine. Patients with distant metastases (8 of 29) had a significantly higher incidence of ras mutations than others (5 of 62, p = 0.01). Patients in classes III and IV also had a higher incidence of mutations (11 of 48) than patients in classes I and II (2 of 43, p = 0.01). The incidence of ras mutations was significantly higher in patients who died of papillary cancer (5 of 15, 33.3%) than in patients who are still alive (8 of 76, 10.5%) (p = 0.02). Kaplan-Meier survival curves also showed a greater mortality from tumor (p < 0.05) and a higher recurrence rate (p < 0.01) in ras-positive tumors than in the ras-negative group. Finally, in studies by multivariate analyses, positive ras mutation and age were shown to be two independent prognostic factors for prediction of death from papillary cancer and recurrence of cancer. CONCLUSIONS: Mutation of N-ras gene at codon 61 is an independent prognostic factor for aggressiveness of papillary thyroid carcinomas. PMID- 7985081 TI - Medullary thyroid carcinoma in multiple endocrine neoplasia types 2A and 2B. AB - BACKGROUND: Considerable emphasis has been placed on early diagnosis and surgery for multiple endocrine neoplasia (MEN)-related medullary thyroid carcinoma (MTC) during the past two decades. Genetic screening now promises earlier and more accurate diagnosis. We examine our experience with MTC in MEN 2A and MEN 2B and assess the benefits of biochemical screening during the past 20 years. PATIENTS AND METHODS: Seventy-seven patients undergoing 63 primary total thyroidectomies and 14 reoperative procedures for MEN-related invasive MTC and/or preinvasive C cell hyperplasia are reported. Fifty-eight patients had MEN 2A and 19 had MEN 2B; 79% of patients had a family history of MTC; 27% had pheochromocytoma, and 25% had hyperparathyroidism. RESULTS: Patients with MEN 2B had more advanced disease than those with MEN 2A, in spite of presentation at a younger age (15 years versus 24 years). Every patient with MEN 2B had invasive carcinoma, whereas 14% of patients with MEN 2A had C-cell hyperplasia without invasive disease. Nodal metastases were found less frequently in MEN 2A (14%) than MEN 2B (38%), and biochemical cure was achieved in 56% of patients with MEN 2A compared with none in patients with MEN 2B. Among patients with MEN 2A the occurrence of invasive carcinoma increased with age (p = 0.0003); 40% of patients for less than 5 years had invasive MTC compared with 100% at more than 20 years. Cause-specific mortality among patients with MEN and invasive tumors at 6, 12, and 18 years was 2%, 4%, and 7%, respectively, lower than that of patients with sporadic MTC (12%, 17%, and 23%, respectively) treated during the same time period (p = 0.028). CONCLUSIONS: Intensive biochemical screening of MEN 2 kindreds for MTC can result in detection of early disease and a significant prospect of surgical cure. Genetic testing promises additional benefits through more reliable detection of preinvasive disease, allowing prophylactic thyroidectomy in infancy. In MEN 2B, MTC is considerably more aggressive than in MEN 2A. A policy of routine thyroidectomy in infants with MEN 2B, regardless of serum calcitonin levels, is justified. PMID- 7985082 TI - Comparative analysis of complications from I-131 radioablation for well differentiated thyroid cancer. AB - BACKGROUND: The decision to extend thyroidectomy to the opposite lobe during resection of well-differentiated thyroid cancer should include an analysis of complications of I-131 radioablation directly related to the thyroid remnant. If significant, then contralateral resection would be indicated. To clarify this issue we studied the incidence of complications of I-131 radioablation in 63 cases of well-differentiated thyroid cancer. METHODS: Retrospective reviews of operative notes, pathology reports, office records, and physician interviews were made. We analyzed operations, complications, and radiation dosing. RESULTS: Procedures included unilateral thyroidectomy, 10 (15.9%); subtotal thyroidectomy, seven (11.1%); near-total thyroidectomy, 25 (39.7%); and total thyroidectomy, 21 (33.3%). The average ablative dose was 101 mCi (range, 30 to 208 mCi). Nineteen percent (12 of 63) of patients had complications including radiation thyroiditis (eight), chronic sialoadenitis (one), odynophagia (one), facial edema (one), and shingles (one). Near-total or total thyroidectomy resulted in significantly fewer complications compared with lesser resections (8.7% versus 47.1%, p < 0.005). CONCLUSIONS: The incidence of complications of I-131 radioablation after thyroidectomy for well-differentiated thyroid cancer is related to the extent of thyroidectomy performed. We recommend contralateral thyroid resection (resulting in a near-total or total thyroidectomy) in patients likely to receive postoperative I-131 radioablation. PMID- 7985083 TI - Fine-needle aspiration of thyroid follicular neoplasm: diagnostic use of thyroid peroxidase immunocytochemistry with monoclonal antibody 47. AB - BACKGROUND: We previously demonstrated that thyroid peroxidase (TPO) immunocytochemistry with monoclonal antibody 47 can help to differentiate benign (staining score, 80% or more) from malignant (staining score, less than 80%) thyroid nodules on fine-needle aspiration (FNA) samples. In the present study we assessed the use of TPO immunocytochemistry in the cytologic diagnosis of thyroid follicular neoplasms. METHODS: A total of 109 histologically proven follicular tumors were studied. There were 60 microfollicular adenomas, 23 atypical adenomas, 17 oncocytic adenomas, and 9 follicular carcinomas. Adequate preoperative FNA samples were available in all cases. TPO immunocytochemistry was performed on one half of the slides. RESULTS: The staining score was less than 80% in all follicular carcinomas, whereas it was 80% or more in 68 of 100 benign tumors. There was no false negative and 32 false positives for diagnosis of malignancy. The false positives were 10 microfollicular adenomas, 13 atypical adenomas, and 9 oncocytic adenomas. TPO immunocytochemistry has a sensitivity of 100% and a specificity of 68% for screening of follicular cancer. CONCLUSIONS: TPO immunocytochemistry with monoclonal antibody 47 on FNA samples is a highly sensitive and fairly specific method to distinguish benign from malignant follicular neoplasms. This technique can help to reduce the number of surgical procedures for benign thyroid nodules without increased risk of overlooking malignancy. PMID- 7985084 TI - Intermediate-risk group for differentiated carcinoma of thyroid. AB - BACKGROUND: We have previously described prognostic factors in differentiated carcinoma of the thyroid gland relating to age, size and extrathyroid extension of the tumor, histologic grade, gender, and distant metastasis. These factors have identified patients in the low-risk group with excellent prognosis and the high-risk group with significant mortality. However, some patients fall within the intermediate-risk category where due deliberation in decision making is required for selection of appropriate treatment. METHODS: A retrospective review of a consecutive series of 1038 previously untreated patients with differentiated carcinoma of thyroid treated during a period of 55 years was undertaken. Data gathered from review of the charts were subjected to univariate and multivariate analysis to assess prognostic factors. On the basis of the patient's age, presence of distant metastasis, and size, grade, and histologic characteristics of the tumor they could be classified into low-, intermediate-, and high-risk categories. Thus 403 (39%) patients were in the low-risk group, 232 (22%) patients in the high-risk category, and 403 (39%) patients in the intermediate risk category. RESULTS: With a median follow-up of 20 years, 99% survival was achieved in the low-risk group, whereas only 57% survived in the high-risk group. Interestingly, in the intermediate-risk category of 403 patients, the 20-year survival was only 85%. Our results clearly identify a distinct intermediate-risk category that includes low-risk patients with high-risk tumor or high-risk patients with low-risk tumor. CONCLUSION: Patients in the intermediate-risk category should be considered for an aggressive treatment approach based on individual prognostic factors. PMID- 7985085 TI - Clinical value of direct DNA analysis of the RET proto-oncogene in families with multiple endocrine neoplasia type 2A. AB - BACKGROUND: The multiple endocrine neoplasia type 2A gene is the RET proto oncogene located on the long arm of chromosome 10, and many mutations within this gene have been reported. METHODS: Peripheral blood DNA was analyzed from 95 members of twelve families with multiple endocrine neoplasia type 2A and known mutations in codon 634 (of exon 11) of the RET proto-oncogene. This region was amplified by the polymerase chain reaction, followed by digestion with Cfo I, which detects restriction sites created by the most common TGC- > CGC mutation and by a TGC- > TGG mutation or with Rsa I, which detects a restriction site created by a TGC- > TAC mutation. RESULTS: Diagnoses were confirmed in 39 patients; 15 of 56 at-risk persons were gene carriers and 41 were noncarriers. The noncarriers included seven persons who had previously undergone thyroidectomies for suspected C-cell hyperplasia but were negative for the RET mutation present in affected members of their families. CONCLUSIONS: Identification of the specific gene alterations within families permits direct DNA diagnosis of at-risk family members. The 41 noncarriers will not require further testing nor need to be concerned about transmitting multiple endocrine neoplasia type 2A to their descendants. The normal DNA findings in seven of these persons emphasize the importance of DNA studies in patients with C-cell hyperplasia but no medullary thyroid cancer at operation. PMID- 7985086 TI - An in vitro model of thyroid neoplasia: permanently transfected FRTL-5 cells with thyroglobulin promoter-cholera toxin A1 subunit minigene. AB - BACKGROUND: Activating mutations of protein Gs alpha that stimulates adenylyl cyclase are present in a subset of thyroid adenomas. Cholera toxin A1 subunit (CT) mimics these mutations via adenosine diphosphate-ribosylation of Gs alpha. METHODS: To test the role of activated Gs alpha in thyroid neoplasia we developed an in vitro model. With molecular genetic techniques a transgene (TG-CT) in which the thyroglobulin gene (TG) promoter directs expression of CT was made. This transgene was transfected into rat thyroid follicular cells (FRTL-5). Integration of TG-CT transgene and its expression were examined. RESULTS: Polymerase chain reaction of DNA from transfected FRTL-5 cells identified the TG-CT transgene in six cell lines. The TG-CT transfected clones exhibited up to a 65-fold (1.29 +/- 0.37 pmols cyclic adenosine monophosphate (cAMP)/micrograms DNA) increase in cAMP over nontransfected FRTL-5 cells (0.02 +/- 0.001 pmols cAMP/micrograms DNA). Insulin, a known stimulator of the TG promoter, further induced CT gene expression and led to a 209-fold (10.43 +/- 0.10 pmols cAMP/micrograms DNA) increase in cAMP over nontransfected cells (0.05 +/- 0.00 pmols cAMP/microgram DNA). CONCLUSIONS: By mimicking a known mutation associated with thyroid neoplasms, these permanently transfected FRTL-5 cell lines will serve as a model to examine the long-term potential neoplastic effects of activated Gs alpha on thyroid follicular cells. PMID- 7985087 TI - Indeterminate fine-needle aspiration biopsy of the thyroid: identification of subgroups at high risk for invasive carcinoma. AB - BACKGROUND: We examined the various cytologic features of indeterminate thyroid fine-needle aspirates along with known clinical and radiologic risk factors to determine whether any parameters were predictive of malignancy. METHODS: Indeterminate fine-needle aspirates were prospectively categorized into four subgroups: (1) suspicious for papillary carcinoma, (2) follicular neoplasm, (3) Hurthle cell neoplasm, and (4) hypercellular follicular aspirates with colloid. Several clinical risk factors were examined, and subgroup comparisons were performed with Fisher's exact test. RESULTS: Of 571 fine-needle aspirate cytologic findings 104 were interpreted as indeterminate for malignancy, and 81 patients underwent thyroidectomy. Invasive cancer was diagnosed in 9 of 10 lesions cytologically suspicious for papillary carcinoma, 8 of 43 follicular neoplasms, 5 of 18 Hurthle cell neoplasms, and 0 of 10 hypercellular aspirates. Cytologic subgroup (p < 0.0001) and age of 50 years or older (p = 0.008) were the only significant predictors of malignancy. When used together, age of 50 years or older and a cytologic diagnosis of follicular or Hurthle cell neoplasm also identified a subgroup of patients at high risk (9 of 20) of invasive malignancy (p = 0.01). CONCLUSIONS: The majority of invasive cancers (18 of 22, 82%) were found in patients whose lesions were suspicious for papillary carcinoma or in patients 50 years or older with follicular or Hurthle cell neoplasms. The risk of carcinoma in these combined subgroups (18 of 30, 60%) warrants early surgical intervention. PMID- 7985088 TI - Role of surgery in stage IE non-Hodgkin's lymphoma of the thyroid. AB - BACKGROUND: Controversy persists regarding the role of surgery in the treatment of stage IE non-Hodgkin's lymphoma of the thyroid. Treatment options vary from complete surgical resection only to needle biopsy as the only invasive procedure required. METHODS: During a 29-year period 15 patients with stage IE non Hodgkin's lymphoma were treated, with complete follow-up available in all patients. All patients had surgical exploration, followed in most cases by radiation therapy and/or chemotherapy. RESULTS: After operation six patients exhibited no gross residual tumor, all with intrathyroid disease, and all remained disease free; five of nine patients with residual disease, all with extrathyroid lesions, had persistent or recurrent disease (p < 0.04). Among patients with residual disease after operation five of six receiving postoperative radiation therapy exclusively have died of or had recurrence of disease, whereas no further persistent or recurrent disease occurred in the three patients who received adjuvant chemotherapy (p < 0.02). CONCLUSIONS: Surgery permitted the distinction between intrathyroid tumor, which may be treatable by local therapy alone, and extrathyroid lesions, which appear to require systemic chemotherapy. Surgery provides not only the same diagnostic ability as needle biopsy but also important therapeutic implications regarding adjuvant therapy. PMID- 7985089 TI - Total thyroidectomy in therapy-resistant Graves' disease. AB - BACKGROUND: Influences of total thyroidectomy have not been evaluated in patients with severe Graves' disease who might respond less satisfactorily to subtotal thyroid resection. METHODS: Thirty-three patients with Graves' disease underwent total thyroidectomy because of persistent endocrine ophthalmopathy (n = 28) or elevated thyrotrophin receptor antibody titers (n = 25) despite a mean of 2 years of thyrostatic therapy. Moreover, six and four patients had undergone radioiodine treatment and subtotal thyroid resection, respectively. Perioperative findings and complications have been investigated, as have influences on endocrine ophthalmopathy and thyrotrophin receptor antibody titers during a mean of 2.5 postoperative years. RESULTS: Total thyroidectomy substantiated mean thyroid weights of 17 gm, 2.3 hours of operating time, and total blood loss of 264 cc. Vocal cord paralysis and vitamin D-treated hypocalcemia occurred in two and three patients, respectively, and invariably persisted less than 6 months. Normalization of elevated thyrotrophin receptor antibody titers occurred in 86% of patients without radioiodine exposure, and stable or improved signs of endocrine ophthalmopathy were found in 96% of patients examined 6 or more months after the operation. CONCLUSIONS: Total thyroidectomy seems to be a surgically safe procedure in complicated Graves' disease and to provide normalization of therapy-resistant thyrotrophin receptor antibody titers. Because favorable influences might also encompass severe endocrine ophthalmopathy, prospective analysis on its efficiency is warranted. PMID- 7985090 TI - Pheochromocytoma as the first manifestation of von Hippel-Lindau disease. AB - BACKGROUND: von Hippel-Lindau disease is an autosomal dominant disorder characterized by the development of hemangioblastomas in the cerebellum, spinal cord, and retina, renal cell carcinoma and cysts, pancreatic cysts, and pheochromocytoma. METHODS: We have studied a series of 36 French patients affected with von Hippel-Lindau disease pheochromocytoma. Thirty (83%) of them were diagnosed as having von Hippel-Lindau disease because the disease occurred in a familial von Hippel-Lindau disease setting; six (17%) were diagnosed as having von Hippel-Lindau disease because they displayed another characteristic manifestation of that disease. RESULTS: The mean age at pheochromocytoma diagnosis was 29 +/- 14 years (5 to 62 years). Bilateral tumors were documented in 15 (42%) cases, paraganglioma was associated with adrenal pheochromocytoma in four cases, and malignant pheochromocytoma occurred in three cases. Prevalence of pheochromocytoma revealing von Hippel-Lindau disease was 20 (53%) out of 36. In six cases pheochromocytoma was the only manifestation of the disease. CONCLUSIONS: In the interest of the patients themselves and of family members who are at risk, search for von Hippel-Lindau disease must be systematic in the presence of pheochromocytoma. Basic checkup may be completed with familial inquiry, ophthalmoscopy, cerebral magnetic resonance imaging, abdominal ultrasonography, and computed tomography-scan for detection of latent lesions. In the future, after characterization of von Hippel-Lindau disease gene mutations, molecular diagnosis is going to be possible in individual patients. PMID- 7985091 TI - Impaired wound healing in Cushing's syndrome: the role of heat shock proteins. AB - BACKGROUND: Glucocorticoids impair wound healing and cause surgical morbidity. Heat shock proteins are essential to cellular stress tolerance and are associated with glucocorticoids. The adrenal heat shock protein response is under hypothalmic-pituitary-adrenal-axis control, whereas the vascular response is associated with alpha-1 receptors. Because heat shock proteins affect cellular stress responses and are under hypothalmic-pituitary-adrenal-axis control in other tissues, we postulated an association between heat shock proteins and glucocorticoids in healing wounds. METHODS: Modified Hunt-Schilling wound chambers were implanted subcutaneously in rats. They received subcutaneous time release dexamethasone (25 mg) or placebo pellets. Wound chamber heat shock protein 25 and heat shock protein 72/73 were serially assayed for 21 days with western analysis and immunocytochemistry. RESULTS: Dexamethasone caused Cushing's syndrome with approximately 10% weekly weight-loss and adrenal atrophy. Total wound tissue decreased 90% with profound differences in molecular wound responses manifested by decreased heat shock protein 25, 72, and 73 in animals treated with dexamethasone despite equal protein loads. Furthermore, dexamethasone caused heat shock protein 72 redistribution by immunocytochemistry. CONCLUSIONS: This study represents the first description of heat shock proteins in a wound healing model and demonstrates tissue-specific decrease of heat shock proteins with glucocorticoid therapy. Thus the heat shock protein response is intimately associated with normal wound healing and is profoundly altered in subjects with Cushing's syndrome. Manipulation of this response may have clinical importance in wound healing. PMID- 7985092 TI - Long-term outcome of bilateral adrenalectomy in patients with Cushing's syndrome. AB - BACKGROUND: Bilateral adrenalectomy provides an effective surgical option for patients with Cushing's syndrome. Knowledge of the long-term outcome of the patient who has undergone adrenalectomy is an important factor in determining management strategy in this situation. METHODS: Fifty consecutive patients undergoing bilateral adrenalectomy (1980 to 1991) were studied. Twenty-five had Cushing's disease, 18 ectopic adrenocorticotrophic hormone production, and seven primary adrenal hyperplasia. Median age was 43 years (range, 14 to 82 years); male-to-female ratio was 13:37. At follow-up 17 patients had died; the remaining 33 were interviewed at a median of 62 months after operation. RESULTS: Operative mortality was 4%. Late mortality included two patients with Cushing's disease who died of progressive pituitary disease and eight patients with ectopic adrenocorticotrophic hormone production who died of metastatic disease. Five-year survival was: 100% for patient with adrenal hyperplasia, 86% for patients with Cushing's disease, and 39% for patients with ectopic adrenocorticotrophic hormone production. Of 33 survivors followed for a median of 62 months, three (9%) were hospitalized with acute steroid deficiency. The principal complaint among survivors was chronic fatigue (60%). Only 10 (30%) patients had no symptoms. No steroid-related complications resulted after 16 surgical procedures subsequently performed. Of 20 survivors of Cushing's disease, three had Nelson's syndrome. CONCLUSIONS: Bilateral adrenalectomy for Cushing's syndrome is associated with occasional morbidity and mortality consequent to adrenal insufficiency. These patients suffered a high incidence of chronic physical complaints that may reflect the residual sequelae of chronic Cushing's syndrome. An active program of long-term rehabilitation is essential. PMID- 7985093 TI - Postoperative acute adrenal failure caused by transient corticotropin deficiency. AB - BACKGROUND: Acute adrenal insufficiency after a surgical procedure or trauma is rarely reported. In recent years, however, we have treated seven patients with acute primary adrenal insufficiency and three patients with secondary adrenal insufficiency who presented with shock after a surgical procedure or trauma. The standard cosyntropin test was misleading for the diagnosis of corticotropin deficiency. METHODS: In this study we measured serum cortisol in patients older than 65 years who had unexplained hypotension after an abdominal surgical procedure. If the serum cortisol was less than 15 micrograms/dl, we performed 1 microgram and standard (250 micrograms) cosyntropin tests and measured thyroxine, thyrotropin, leutinizing hormone in all patients, and free testosterone in men. RESULTS: We identified five (5%) of 105 patients after an operation who displayed evidence of corticotropin deficiency (i.e., serum cortisol < 15 micrograms/dl during hypotension, prompt hemodynamic improvement with glucocorticoid therapy, and normal response to standard dose cosyntropin). In these patients 1 microgram cosyntropin produced abnormal peak cortisol levels. These patients also had thyrotropin or leutinizing hormone deficiency. After recovery the low hormone levels improved or became normal. CONCLUSIONS: Postoperative adrenal insufficiency, particularly that caused by transient corticotropin deficiency, is more common in patients than currently recognized. The 1 microgram cosyntropin test may be more sensitive than the standard test for identifying secondary adrenal insufficiency. PMID- 7985094 TI - The predictive value of diagnostic tests for pheochromocytoma. AB - BACKGROUND: Ascertaining or excluding a pheochromocytoma may be difficult. The purpose of this study is to identify preoperative tests that are good predictors of a pheochromocytoma. METHODS: Patients presumptively diagnosed with a pheochromocytoma based on clinical assessment, plasma or urinary catecholamines, computed tomography, or magnetic resonance imaging were analyzed. The sensitivity, specificity, positive, and negative predictive values were determined for each test based on the pathologic finding of a pheochromocytoma. Data were analyzed with Student's t test or Fisher's exact test. RESULTS: Of 14 patients, seven had pathologically proven pheochromocytomas, whereas three had cortical adenomas. In four patients, a pheochromocytoma was excluded by repeat testing. The 24-hour urinary mean metanephrine levels were significantly different between patients with and without pheochromocytomas (5.8 micrograms vs 0.5 micrograms, p = 0.05) and had the best positive predictive value (83%) and negative predictive value (100%) of the biochemical tests. T2-weighted magnetic resonance imaging had a 100% positive and negative predictive value. Age, sex, symptoms, blood pressure, tumor location, tumor size, and plasma catecholamine levels could not accurately predict or exclude a pheochromocytoma. CONCLUSIONS: T2-weighted magnetic resonance imaging is the imaging study of choice for predicting a pheochromocytoma. The 24-hour urinary metanephrine level is the single best biochemical indicator of a pheochromocytoma. Plasma catecholamine levels and computed tomography are not helpful in diagnosing or excluding a pheochromocytoma. PMID- 7985095 TI - Hepatic arterial chemoembolization for metastatic neuroendocrine tumors. AB - BACKGROUND: Patients with neuroendocrine neoplasma, even with metastases to the liver, often have indolent disease and are treated conservatively. However, when debilitating symptoms from hormonal syndromes or mass effect arise, more aggressive treatment may be warranted. METHODS: Thirty-nine chemoembolization procedures were performed in 30 patients with significant symptoms, with carcinoids and islet cell tumors. An emulsification of intraarterial doxorubicin, iodized oil, and water-soluble contrast was followed by embolization with absorbable gelatin powder or pledgets. RESULTS: Twenty-seven patients exhibited subjective improvement in clinical symptoms. Hormonal markers and/or tumor size decreased by at least 50% in 79% of patients. Inclusion of minor responses raises this to 92%. Seven complications were noted, and no procedure-related deaths occurred. Median survival was 24 months after chemoembolization or 53 months after diagnosis. Computed tomographic features of tumor vascularity, distribution of metastatic lesions, and distribution of ethiodized oil were not clearly correlated with outcome. Presence of a nonresected primary tumor had a negative effect on survival. CONCLUSIONS: Compared with previously described treatments for neuroendocrine liver metastases, this technique appears to be more effective and to be associated with less morbidity, and is recommended for patients with significant symptoms who have failed to respond to more conservative therapy and who are not surgical candidates. PMID- 7985096 TI - Scintiscans and carcinoid tumors. AB - BACKGROUND: The presence of somatostatin receptors on carcinoid tumors mediates imaging of tumor extent and inhibition of tumor growth and marker secretion. This prospective study aimed to evaluate radiolabeled somatostatin analog scans in the therapeutic workup of carcinoids. METHODS: Twenty-one patients with carcinoids underwent 26 scans with iodine octreotide or indium pentetreotide. The results for tumor and metastases imaging were analyzed and compared with those of a short inhibition test of marker secretion and with those of metaiodobenzylguanidine scan. RESULTS: The sensitivity for obtaining images of the overall 43 tumor sites was 72%. We had no false-positive results. Unknown tumor sites were discovered in three patients. The results were slightly better with indium pentetreotide and metastases imaging. A positive scan did not always preclude responsiveness to the functional effect of octreotide. Results of somatostatin analog scans were better than those with metaidobenzylguanidine. The two techniques were complementary in one patient. CONCLUSIONS: The choice of treatment for patients with carcinoid tumors should benefit from functional inhibition test with octreotide and from indium pentetreotide and metaidobenzylguanidine scans. PMID- 7985097 TI - Apparent lymph node primary gastrinoma. AB - BACKGROUND: The existence of lymph node (LN) primary gastrinoma as a cause of Zollinger-Ellison syndrome is controversial. We reviewed our experience with patients in whom gastrinomas were identified and excised only from LNs. METHODS: From 1982 to 1992, 110 patients with ZES underwent exploration for gastrinoma and 21 (19%) had disease limited to one or more LNs. Standardized exploration included intraoperative ultrasonography, intraoperative endoscopy with transillumination and exploratory duodenotomy in 86%, 67%, and 24% of patients, respectively. Each patient underwent yearly biochemical and radiologic follow-up. RESULTS: Thirteen patients (62%) with a median follow-up period of 5.8 years had an initial biochemical cure, whereas eight patients (38%) with a median follow-up period of 3.6 years had persistent disease. Of the 13 patients whose condition initially returned to normal, four have had biochemical recurrence, with a median time to recurrence of 4.2 years and a median follow-up period of 7.4 years. Nine patients (43%) remain biochemically cured, with a median follow-up period of 5.3 years. CONCLUSIONS: Resection of apparent LN primary gastrinoma is warranted, because 43% of those who underwent resection had no evidence of disease, with a median follow-up period of 5.3 years. PMID- 7985098 TI - Role of endoscopic ultrasonography in the localization of insulinomas and gastrinomas. AB - BACKGROUND: We have previously found selective venous sampling to be the most sensitive method to localize otherwise occult functioning endocrine tumors. However, recently we have used endoscopic ultrasonography (EUS) as the initial and in some cases the only localization study in the preoperative evaluation of proven insulinomas and of selected cases of gastrinoma. METHODS: All patients referred between April 1993 and April 1994 with a subsequently confirmed diagnosis of organic hyperinsulinism or Zollinger-Ellison syndrome (ZES) underwent EUS. Ten patients with insulinomas and six with gastrinomas were studied. Only one patient with ZES had multiple endocrine neoplasia type I. Patients with negative EUS findings had additional localization procedures including angiography and arterial stimulation tests. All but one patient underwent surgical exploration. RESULTS: Solitary insulinomas were found in all 10 patients. EUS correctly identified and localized the insulinoma in seven (70%) of 10 patients but failed to identify two pedunculated insulinomas that were easily found at exploration. Because of an incomplete examination, a single insulinoma was not detected within the parenchyma. The EUS examination correctly excluded the pancreatic gastrinomas in five patients. The sixth patient, who had multiple endocrine neoplasia type I, had two 0.5 cm tumors in the head. CONCLUSIONS: EUS is a sensitive and cost-effective technique for localization of insulinomas and may be the only study needed. In patients with ZES a negative pancreatic result suggests the likelihood of a duodenal or other extrapancreatic tumor. PMID- 7985099 TI - Detection of occult gastrinomas with iodine 125-labeled lanreotide and intraoperative gamma detection. AB - BACKGROUND: Surgical exploration for gastrinoma has a high failure rate because of small primary tumors and occult metastasis. Despite extensive preoperative and intraoperative tumor localization, only 30% to 40% of patients with gastrinoma are cured by surgery. Two patients with unlocalized gastrinomas were studied with intraoperative gamma detection of an iodine 125-labeled somatostatin analog, lanreotide, to localize their tumors. METHODS: Both patients were challenged before operation with 100 micrograms of octreotide acetate, and both had circulating gastrin levels suppressed by greater than 50%. Iodine 125-labeled lanreotide (100 to 150 muCi) was injected during exploration, and an intraoperative gamma detector was used to detect tumor binding of the analog. RESULTS: In patient 1 a single source of increased counts was discovered in a retroduodenal lymph node, which was excised; no other tissue was removed. Histologic study of this node failed to demonstrate tumor; however, the patient's gastrin level was normal (63 pg/ml) 4 months after operation. In patient 2 five areas of increased counts were discovered and excised. Three of these five areas had visible tumor on microscopic examination. Three months after operation the patient's fasting gastrin level was 103 pg/ml. CONCLUSIONS: Intraoperative gamma detection of radiolabeled peptides may allow the localization of occult tumors that contain specific peptide receptors. PMID- 7985100 TI - Peptide YY immunoneutralization inhibits meal-induced absorption in vivo. AB - BACKGROUND: Plasma peptide YY (PYY) levels rise after a meal and have recently been shown to increase small bowel-absorption. The purpose of this study was to determine whether immunoneutralization of PYY would block postprandial absorption in vivo. METHODS: Exteriorized, neurovascularly intact jejunal and ileal segments (25 cm) were created in six mongrel dogs. After a 2-week recovery luminal perfusion with an isotonic buffer, containing [14C]-polyethylene glycol as a volume marker, was used to analyze water and sodium flux after an oral meal. Each meal was accompanied by either intravenous anti-PYY (0.5 mg.kg-1.h-1) or nonspecific immunoglobulin IG (control). PYY antibody binding was determined by radioimmunoassay. RESULTS: Displacement studies showed complete PYY neutralization. In control experiments feeding increased absorption of sodium and water in both segments. PYY immunoneutralization had no effect on jejunal absorption but significantly diminished ileal absorption (p < 0.05). CONCLUSIONS: These results suggest that PYY acts selectively in the ileum to increase postprandial fluid and electrolyte absorption after a meal. Agents directed at PYY-stimulated absorption may prove to be of therapeutic benefit in patients with malabsorptive conditions. PMID- 7985101 TI - "Asymptomatic" primary hyperparathyroidism: is parathyroidectomy indicated? PMID- 7985102 TI - Cost of unsuccessful surgery for primary hyperparathyroidism. AB - BACKGROUND: Surgery for primary hyperparathyroidism demands skill and experience. The monetary and personal costs of unsuccessful surgery are investigated here. METHODS: We reviewed 47 consecutive patients operated on by one surgeon during a period of 16 months, including their clinical data and medical costs of their treatment. RESULTS: All 39 patients without previous operation were normocalcemic after operation, with no recurrent nerve injury nor hypoparathyroidism. Of the eight who had undergone previous operation elsewhere, seven had abnormal glands that should have been resected at the initial operation, and hypoparathyroidism developed in two patients. Total costs of reoperative parathyroid surgery were more than twice the cost of an initial operation (median, $8383 versus $3948, p < 0.001) because of the cost of radiologic studies (median, $3378 versus $43, p < 0.001). CONCLUSIONS: (1) An experienced parathyroid surgeon can consistently cure hyperparathyroidism at the initial operation. (2) The majority of patients referred for hyperparathyroidism not cured by previous operation have glands in usual anatomic locations. (3) The cost to the patient of an inadequate initial operation includes the physical effects of remaining hyperparathyroid, additional time off work, potentially invasive localization testing, reoperative surgery with increased risk of complications, and substantial expense. Initial parathyroid surgery should be performed by surgeons experienced and proficient in its practice. PMID- 7985103 TI - Use of preoperative fine-needle aspiration in patients undergoing reoperation for primary hyperparathyroidism. AB - BACKGROUND: Neck reexploration for primary hyperparathyroidism has a lower success rate and greater morbidity than initial exploration because of scarring and distortion of tissue planes and the possibility of a parathyroid neoplasm located in an ectopic or unusual position. Although the use of standard noninvasive imaging studies for reoperative parathyroid surgical procedure is well accepted, the use of invasive studies to localize parathyroid neoplasms, particularly percutaneous aspiration of potential lesions, is controversial. In this report we analyze the results and morbidity in patients undergoing fine needle aspiration before neck reexploration. METHODS: From 1982 to 1993, 255 patients underwent reexploration for persistent or recurrent hyperparathyroidism at the National Institutes of Health. Of these 255 patients 42 underwent 44 preoperative fine-needle aspirations by ultrasonography or computed tomography guidance in an attempt to localize a parathyroid neoplasm. The aspirated contents were then analyzed for parathyroid hormone content. RESULTS: Of the 44 aspirations 26 (59%) were true positives with no false positives. Of 18 negative fine-needle aspirations, 11 (25%) were false negatives, and seven (16%) were true negatives. The specificity and sensitivity of percutaneous fine-needle aspiration were 100% and 70%, respectively. CONCLUSIONS: Percutaneous fine-needle aspiration for parathyroid hormone is a safe, well-tolerated technique that is highly specific and allows a directed surgical resection avoiding further invasive workup when the aspirate is positive. PMID- 7985104 TI - Parathyroid imaging with technetium-99m-sestamibi: an initial institutional experience. AB - BACKGROUND: The ideal method for preoperative localization of abnormal parathyroid glands has yet to be determined. Technetium-99m-sestamibi, previously used for myocardial perfusion studies, has recently been introduced for parathyroid imaging. METHODS: From August 1991 to September 1993, 44 patients underwent Tc-99m-sestamibi scanning (45 scans) and surgical exploration for hyperparathyroidism at our institution. These 44 patients form the database for this retrospective study. Twenty-eight patients had persistent hyperparathyroidism, six had recurrent disease, three had prior thyroid operation, and seven underwent first time neck operations. The nature of disease was complex and varied: single gland, 26; primary hyperplasia, 5; multiple endocrine neoplasia type 1, 5; familial, 3; secondary or tertiary, 5. One patient with single gland disease and one patient with multiple endocrine neoplasia type 1 had parathyroid carcinoma. All patients had biochemical confirmation of hyperparathyroidism. RESULTS: Twenty-six (58%) of 45 scans accurately predicted the location(s) of all abnormal gland(s) involved (true positive). Surgical removal of these glands was curative. Sixteen (36%) of 45 scans were false negative because they did not show all abnormal glands involved; however, 7 of these 16 scans did localize at least one abnormal gland. The overall sensitivity of this test was 62% when all abnormal glands were considered but increased to 79% with the demonstration of at least one abnormal gland. These values increased to 80% and 90% (p = 0.03), respectively, in the last 20 patients when the injected dose of Tc-99m-sestamibi was increased from 10 to 15 mCi. Thirty-seven of 44 patients were cured after operation. Six of the seven patients who experienced surgical failure had multigland disease, one of which was malignant. Sestamibi scans correctly identified abnormal cervical glands in 18 (58%) of 31 patients and abnormal mediastinal glands in six (75%) of eight patients. CONCLUSIONS: Tc-99m-sestamibi scanning is helpful in the reoperative setting as an adjunct to localizing abnormal parathyroid tissue. A higher percentage of positive tests occurs in patients with mediastinal and single gland disease. A higher dose of Tc-99m-sestamibi (15 mCi) significantly improves test sensitivity. PMID- 7985105 TI - Positron emission tomography with 11C-methionine in hyperparathyroidism. AB - BACKGROUND: Positron emission tomography (PET) has not been evaluated for preoperative localization and functional characterization of the parathyroid tissue in hyperparathyroidism. METHODS: Images of the neck and upper mediastinum of 23 patients with hyperparathyroidism were obtained by PET after intravenous administration of 400 to 800 MBq L-[methyl-11C]-methionine. The investigation was repeated in six patients after Na2-ethylenediamine tetraacetic acid infusion, whereby stable 65% to 157% rise in intact serum parathyroid hormone values was attained. RESULTS: Parathyroid surgical procedure revealed single (21 patients) or two enlarged parathyroid glands (two patients) that were characterized as chief cell adenoma (n = 13), hyperplasia (n = 10), or carcinoma (n = 2) and weighed 80 to 6000 mg. Twenty (80%) of these glands were localized by PET. The remaining examinations (20%) were false negative and mainly encompassed small parathyroids in juxtathyroid position. Among 15 patients undergoing parathyroid reoperation true-positive localizations were obtained for 87% of the glands. The images displayed lower tracer uptake in residual thyroid lobes (n = 40), esophagus, and cervical vertebrae. Na2-ethylenediamine tetraacetic acid infusion failed to enhance parathyroid uptake values. Ultrasonography, computed tomography, technetium-thallium scintigraphy, and venous sampling revealed 25% to 53% of the pathologic parathyroid tissues of the patients undergoing reoperation and was largely complementary to PET. CONCLUSIONS: The results suggest that PET may provide novel possibilities for the imaging of pathologic parathyroid glands in hyperparathyroidism. PMID- 7985106 TI - Localization and operative management of undescended parathyroid adenomas in patients with persistent primary hyperparathyroidism. AB - BACKGROUND: Between 5% and 10% of patients who undergo cervical exploration for primary hyperparathyroidism will have persistent or recurrent hyperparathyroidism. Many of these patients have parathyroid tumors in unusual locations. One such site of ectopic parathyroid tissue is an undescended parathyroid adenoma at or superior to the carotid bifurcation. We describe our experience with the preoperative localization and surgical management of undescended parathyroid adenomas. METHODS: From 1982 to 1993 a consecutive series of 255 patients have undergone localization studies and surgical exploration for persistent or recurrent hyperparathyroidism at the Clinical Center of the National Institutes of Health. Operative strategy was determined by review of the patient's surgical history, disease reports, and data from localizing studies. Patients with an undescended parathyroid adenoma identified before the operation were examined with a direct approach high in the neck. Patients who did not have definitive preoperative localization were explored with the previous transverse cervical incision. RESULTS: Seventeen undescended parathyroid adenomas were identified in 255 patients. Thirteen (76%) of 17 patients had an undescended parathyroid adenoma precisely localized before the operation and were examined via a limited, oblique incision high in the neck anterior to the sternocleidomastoid muscle. In the 13 patients who had undergone accurate localization before the operation, the median operative time was 75 minutes compared with 235 minutes for four patients who did not have an undescended parathyroid adenoma identified before the operation and were examined via a previous transverse cervical incision. All patients were cured of their hyperparathyroidism. CONCLUSIONS: Undescended parathyroid adenomas were the cause of failed cervical exploration in 17 (7%) of 255 patients. Accurate preoperative localization of these lesions is possible in most cases with a combination of noninvasive and invasive modalities. Successful preoperative localization can convert a prolonged exploration of the neck and mediastinum into a brief, curative procedure with minimal morbidity. PMID- 7985107 TI - Persistent and recurrent sporadic primary hyperparathyroidism: histopathology, complications, and results of reoperation. AB - BACKGROUND: Our purpose was to analyze the causes of persistent and recurrent sporadic primary hyperparathyroidism (PD and RD). METHODS: The histopathology, complications, and results of reoperation were studied. Five hundred sixty-eight patients with primary hyperparathyroidism were operated on initially by one surgeon and underwent follow-up examination for 3.7 +/- 3.8 years. During the operation, all parathyroids were sought and confirmed by biopsy. Enlarged glands were resected, and subtotal parathyroidectomy was done for multiglandular disease (hyperplasia). RESULTS: The cure rate after the initial surgical procedure was 96.4%, PD = 2.8% (16 of 568). At reoperation (10 of 16), nine of 10 were cured (90%) (two adenomas, six hyperplasias, one lung carcinoma). RD was documented (at years 4, 4, 10, 15, 16) in five (0.9%) patients, one with parathyroid carcinoma and four with hyperplasia. Thirty-five patients with PD and two patients with RD were referred for reoperation: 17 with adenomas (eight mediastinal) and 18 with hyperplasias (one mediastinal gland). Preoperative calcium level was higher for PD (12.57 mg/dl) and RD (13.89 mg/dl) versus all cases (12.19 mg/dl) (p < 0.03 and p < 0.0005, respectively). After reoperation, normocalcemia was achieved in 47 (92.%) of 51 patients with PD or RD. Transient hypocalcemia occurred in 22% of patients (permanent, 2.0%) and transient hoarseness in 2.0% of patients (no permanent nerve damage). Permanent hypocalcemia and nerve damage after 568 initial operations were 0% and 0%, respectively. Two perioperative deaths occurred. CONCLUSIONS: We conclude that inadequate neck exploration or resection of hyperplastic tissue accounts for most cases of PD and RD. Optimal results necessitate intraoperative identification of all parathyroids whenever possible, with minimal morbidity. PMID- 7985108 TI - Thoracoscopic excision of enlarged mediastinal parathyroid glands. AB - BACKGROUND: Most abnormal parathyroid glands can be removed through the neck, but those deep in the chest have required sternotomy or thoracotomy. To avoid the morbidity of these open procedures, ectopic parathyroid glands deep in the chest were removed with video-assisted thoracoscopy. METHODS: Two patients with persistent primary and two with persistent secondary hyperparathyroidism had technetium-thallium scintigraphy and computed tomography of the chest to localize their ectopic glands. Video-assisted thoracoscopy was used for operative removal of these glands in each patient. RESULTS: Parathyroid scans identified a mediastinal gland that was confirmed and localized precisely by the computed tomography scan. An enlarged ectopic gland weighing 1 to 2 gm was removed from each patient with normalization of serum calcium level. Glands were found by the main pulmonary artery, aortopulmonary window, ascending aorta, and aortic arch. One patient had recurrent disease 9 months later. CONCLUSIONS: Removal of parathyroid glands deep in the chest with video-assisted thoracoscopy is a safe and successful alternative to median sternotomy. PMID- 7985109 TI - [Congress: Minister: no ideological experiments]. PMID- 7985110 TI - [Breast feeding should be reinforced]. PMID- 7985111 TI - [Priority setting. Card file cabinet in a rare blue color]. PMID- 7985112 TI - [Professional nursing guidance--also for somatic nurses]. PMID- 7985113 TI - [Health administration's role as a rattle shaker?]. PMID- 7985114 TI - [Refugees--a successful cultural meeting]. PMID- 7985115 TI - [Buffet service--a dubious success]. PMID- 7985116 TI - [Congress: nurses are bearers of development]. PMID- 7985118 TI - [Congress: management let us down]. PMID- 7985117 TI - [Congress: pools instead of local wages]. PMID- 7985119 TI - [Congress: the fight goes on]. PMID- 7985120 TI - [The results of a multicenter cooperative study on treating acute myeloid leukemias in adults]. PMID- 7985121 TI - [The efficacy of artificial pulmonary ventilation in acute respiratory failure in patients with hemoblastoses]. AB - The authors review pulmonary effects achieved for 3 years in hemoblastosis patients subjected to artificial lung ventilation (ALV). Out of 44 patients treated the response to ALV was obtained in 7 (16%). Prior to ALV, two of them had granulocyte count under 0.5 x 10(-9)/1. ALV was discontinued in them after recovery of normal granulocyte count. Three patients (7%) survived 6 months and longer. Problems of differential diagnosis in different variants of acute respiratory failure in hemoblastosis patients and ALV potentialities are discussed. PMID- 7985122 TI - [Experience with the use of different methods of bone marrow separation and cryopreservation at the bone marrow transplantation centers of the Regional Hospital of the City of Bolzano (Italy) and of the Saint Petersburg Institute of Hematology and Blood Transfusion]. PMID- 7985123 TI - [Kidney involvement in idiopathic myelofibrosis]. AB - Functional potential of the kidneys, principal causes of nephrolithiasis and chronic renal failure were investigated in 30 idiopathic myelofibrosis (IMF) patients by combination of different modalities, sonography, in particular. Sonography proved highly informative in diagnosis of nephroliths the formation of which is attributed to derangement of uric acid metabolism, of renal elimination, and anatomical features of the urinary system. A correlation analysis between various factors showed that in IMF hyperuricemia, hyperfiltration and proteinuria damage cortical and medullary layers of the kidneys provoking their functional defects and development of chronic renal failure. PMID- 7985124 TI - [Cumulative radiation dosage and epidemiological research in the Chernobyl region]. AB - Individual biological dosimetry covering chromosomal analysis and electronic paramagnetic resonance spectrometry has been performed in 1300 subjects exposed to ionizing radiation after the Chernobyl accident. Cumulative radiation doses above 40 ImC were registered in 5%, about 100 ImC in 1% of the examinees. In 1% of cytogenetic investigations there appeared multiaberrant cells indicative of hot particle incorporation. Regional epidemiologists do not record changes in the incidence of hematological diseases. This may be explained by a small percent of the dose carriers, rare occurrence of hematological disorders and the time of radiation-induced oncogenic effects. The above representative group exposed to definite radiation doses may serve the subject of epidemiological surveys on the role of low-dose and low-rate radiation in pathogenesis of human diseases. PMID- 7985125 TI - [The intensification of the therapy of chronic myeloleukemia by taking into account the factors prognostic of the course of the disease]. AB - A multifactorial computer analysis of current modalities in relevant treatment performed for 208 patients with chronic myeloid leukemia (CML) has revealed a close relationship between the set of unfavourable factors upon the diagnosis, choice of treatment and the patients' survival. For groups of patients with a standard CML risk it is preferable to use monotherapy. More intensive treatment (polychemotherapy) is indicated in the disease progression. The patients at moderate and high CML risk are recommended to be treated intensively (polychemotherapy, polychemotherapy+leukocytapheresis, splenectomy) from the start, that is upon CML diagnosis. The above approach promotes longer survival of CML patients. PMID- 7985126 TI - [The clinicoimmunological characteristics of blast transformation in lymphosarcomas]. AB - The authors studied a blast cell immunological phenotype in 50 adults with lymphosarcoma undergoing leukemization following the pattern of acute leukemia. Among the patients there were 12 females and 38 males aged 14-61. Immunological phenotyping of tumor cells was performed using a panel of monoclonal antibodies to T- and B-lymphocyte antigens, to myelomonocytic cells, some nonlinear and activation antigens. T, B and zero variants of blast cells were identified. Occasionally, blast cells carried nonlymphoid antigens and those corresponding to the common lymphosarcoma subvariant. Leukemization in the direction of lymphoblastic leukemia is associated with greater frequency of lymphosarcoma T subvariant (46%). B-cell and zero subvariants occurred in 28% and 20% of the patients, respectively. The number of complete remissions in the group of patients with T-cell subvariant was greater than in the group with B-cell subvariant. The survival in these two groups, however, was almost similar (median up to 8-12 months). Further studies into lymphoblastic leukemization immunophenotyping can help design programs of differentiated polychemotherapy. PMID- 7985127 TI - [The degree of malignancy of lymphomas and the adequacy of cytostatic treatment]. PMID- 7985128 TI - [Hairy-cell leukemia (a review of the literature and the authors' own data)]. AB - Gene engineering interferon made in Russia (reaferon, realdiron) was given to 40 patients with hairy-cell leukemia. Complete and partial remissions were achieved in 56% and 28% of the patients, respectively. Minimum effect was reported in 3% of the cases. In 5 cases with primary resistance or recurrences the authors used pentostatin which produced complete remissions in all the five patients. PMID- 7985129 TI - [The morphofunctional characteristics of the mononuclear phagocytes in the concentrated venous blood leukocytes of patients with histiocytosis]. AB - Morphological and cytochemical examinations of mononuclear phagocytes (MP) from venous blood leukoconcentrate were carried out in 25 patients with chronic monocytic leukemia, 7 patients with malignant histiocytosis, 3 patients with Langerhans' cell histiocytosis and 26 patients with reactive proliferations of the cells belonging to MP system associated with autoaggressive, infectious diseases or tumors. Morphofunctional features of MP from the patients with tumor and reactive histiocytosis may serve additional criteria in differential diagnosis of the diseases in which pathological process runs with participation of MP system cells. PMID- 7985131 TI - [The use of a daily dose of methylprednisolone (Medrol) once in treating hemoblastoses]. PMID- 7985130 TI - [The use of Cardioxan as a cardioprotective agent during antitumor chemotherapy]. PMID- 7985132 TI - [The characteristics of iron metabolism in B12-deficient anemias (an evaluation of the functional status of megaloblastic erythropoiesis)]. AB - The review of the literature data and the evidence obtained on 85 own patients with B12-deficiency anemia concerning iron metabolism underlie 3 variants proposed by the authors: pronounced manifestations of secondary sideroachresia before B12 therapy, utilization iron deficiency upon B12 introduction, dimorphic anemia (development of megaloblastic erythropoiesis in prior iron deficiency). The causes of megaloblastic erythropoiesis incompetence (slow rate, hemolytic component, secondary sideroachresia) are discussed. PMID- 7985133 TI - [Changes in the composition and properties of the joint contents in hemophilic arthropathies during local invasive therapy]. AB - An immunological study has been made in 47 hemophiliacs with arthropathies receiving local invasive therapy. Joint contents were examined in 20 patients with acute hemarthrosis, 10 patients with exudative synovitis and 11 ones with proliferative synovitis. Under the protection of cryoprecipitate (5 U/kg) all the patients underwent joint puncture with removal of the contents, lavage of the synovial cavity and intraarticular injection of 50 mg of hydrocortisone. Arthropathy activity proved most active in patients with proliferative synovitis. Introduction of local invasive therapy early in hemarthrosis course arrests immune inflammation. Delayed punctures are less effective. Local immunological responses, as shown by repeated punctures, noticeably reduced, at puncture 3-4 the contents were small, immune complexes and immunoglobulins decreased significantly. PMID- 7985134 TI - [Autoimmune thyroiditis in patients with hematologic diseases]. PMID- 7985135 TI - [The current possibilities for using plasmacytapheresis (hemapheresis) methods]. PMID- 7985136 TI - [The current diagnosis of acute nonlymphoblastic leukemias]. AB - The paper presents the results of the retrospective study of blast cells from 377 patients with acute nonlymphoblastic leukemia (ANLL). Morphocytochemical, immunological, cytogenetic assessments and cloning in semisolid agar were employed. The authors specify blast characteristics with reference to ANLL variants according to the FAB classification, define diagnostic criteria for poorly differentiated myeloblastic (MO), erythroblastic (M6) and megakaryoblastic (M7) leukemia, hybrid variants. PMID- 7985137 TI - [Therapeutic plasmapheresis in immune complex diseases]. AB - We studied the dependence of the plasma protein and volume on the exfusion volume, type and composition of the substitution solution in 140 plasmapheresis procedures given to patients with immune thrombocytopenic purpura and bronchial asthma. The change of blood protein system corresponded to the procedure regime. The procedure does not entail adverse reactions if it removes up to 30% of the plasma circulating volume (replacement with salt solution), 50% of the plasma circulating volume (replacement with dextran solution) or 95% of that with replacement with albumin. We have tested 3 simple mathematic models for postplasmapheresis proteinemia and recommend the regression equation Ct = a0 + a1.Co as the most adequate model. PMID- 7985138 TI - [Hyperlipidemia and glomerulosclerosis in nephropathies: clinicomorphological comparisons]. AB - An extracellular matrix (collagens I, III, IV) was studied in the glomeruli of patients demonstrating glomerular low density lipoproteins (LDL) and free of them. These two patients' groups were not found significantly different by age, nephropathy duration, blood pressure, serum concentrations of creatinine, triglycerides, HDL cholesterol. The LDL deposit group differed by longer duration of the nephrotic syndrome, higher 24-h proteinuria, lower serum albumin levels, higher total cholesterol in the serum and the proportion VLDL and LDL cholesterol to HDL cholesterol. They had noninflammatory nephropathies more frequently, collagen IV accumulated in the glomerulus more actively, there appeared interstitial collagens I and III. The discussion concerns the role of hypercholesterolemia with the above proportion of cholesterols, its duration, a type of cells dictating mesangial proliferation, in the development of LDL deposit-induced glomerulosclerosis. PMID- 7985139 TI - [The organization of ambulatory services for patients with rheumatoid diseases at an industrial enterprise]. AB - The authors have elaborated a complex of economically profitable organizational and medical measures aimed at stabilization or reduction of temporary disability due to osteoarthrosis (OA) in workers of an industrial enterprise. As a result of epidemiological studies it has been established that at the enterprise under study the OA incidence exceeded the general populational one more than 5-fold, with the number of cases and days of temporary disability due to OA ranking the first among the leading causes of temporary disability. The complex of medico organizational and treatment-and-prophylactic measures closely related to the industrial process and taking account of the patients' interests made it possible to stabilize, within a period of 6 months, the characteristics of temporary disability and to reduce economic losses due to OA. PMID- 7985140 TI - [The manifestation of immune reactions and the chromium content of the blood in patients with occupational allergic dermatoses]. AB - One of the mechanisms responsible for occupational dermatoses of constructors in contact with Cr-containing substances is supposed to be antibodies production as a result of Cr ion migration in the blood. The authors' measurements led them to the conclusions that no significant rise in blood Cr content occurs with an increase in the service duration, there is a close relationship between Cr blood concentrations and specific skin tests as well as between blood Cr and allergic manifestations. In patients with initial and established forms of occupational dermatosis the number of positive responses to Cr skin tests and frequency, intensity of allergic reactions grow with elevation of Cr concentrations in the blood. It is inferred that the test for blood chromium may serve an additional criterium of early diagnosis of occupational dermatosis. PMID- 7985141 TI - [Protracted hypochondriacal reactions (based on the type of hypochondriacal development) in myocardial infarct patients]. AB - Clinical follow-up, MPT, clinical and instrumental cardiological evidence is available for 30 postmyocardial infarction patients. They exhibited hypochondriac reactions which persisted for more than 6 months. Three types of such reactions were recognized: somatization (I), cenesthetic (II), overvalued (III). I reactions were associated with homonomous body sensations, anxious and conversion disorders, avoidance behavior. II reactions cover heteronomous sensations with attendant autoaggressive behavior. Patients with reactions III had dominant ideas of complete health recovery, delirium-like fantasies. It is established that I reactions arise in personalities with neurotism radical, reactions II in those with rigidity and eccentric behavior, reactions III in patients with rigidity and conformity. PMID- 7985142 TI - [A case of an attempt on the life of an individual by the use of a gamma irradiator]. PMID- 7985143 TI - [The Conference on Mental Disorders and Cardiovascular Pathology]. PMID- 7985144 TI - [The possibilities of using intermittent normobaric hypoxia for treating hypertension patients]. AB - The response to intermittent normobaric hypoxia (INH) created in breathing gas hypoxia mixture (10% oxygen, 90% nitrogen) was evaluated in 123 patients with essential hypertension stage I and II. Hypoxia adaptation effects on central hemodynamics, physical performance, kinetics of oxygen exchange were studied. A pronounced response to INH persistent for 6 months was demonstrated in 80.5% of the patients. The reduction of the arterial pressure resulted from different mechanisms depending on hemodynamic type. Physical performance of the patients rose, oxygen consumption and transport normalized. PMID- 7985145 TI - [The clinical and hemodynamic effects of enalapril and its influence on the peri infarct area in patients with an acute myocardial infarct]. PMID- 7985146 TI - [The effect of transcardiac galvanization on the size of the necrotic mass and on the central hemodynamic indices in patients with an acute myocardial infarct]. AB - The authors examined 110 males and females admitted to hospital within 6 hours since the onset of new macrofocal anterior myocardial infarction running without complications. All the patients underwent transcardiac galvanization (TG) in the initial disease hours. Precardiac mapping, tetrapolar rheography and clinical observation provided evidence on TG course action on the necrosis mass, central hemodynamics and clinical appearance of the disease in the acute and postinfarction periods. TG promoted faster and more marked improvement of cardiac muscle contractility, attaining higher functional level of inotropic myocardial activity up to the disease month 6. This was associated with alleviation of circulatory disorders both at the hospital and postinfarction stage. The response to course TG results from cardioprotective action of constant electric current on ischemic myocardium which limits the zone of the lesion thus reducing early fatal cases number and preventing cardiogenic shock. PMID- 7985147 TI - [The efficacy of 2 new drug forms of isosorbide-5-mononitrate in patients with stable stenocardia of effort]. PMID- 7985148 TI - [The chronobiological trend in medicine: biologically controlled chronophysiotherapy]. PMID- 7985149 TI - [The effect of molsidomine preparations on the coronary and myocardial reserves of patients with IHD complicated by circulatory failure]. AB - Molsidomine drugs corvaton and sidnopharm were given as monotherapy to 95 coronary heart disease (CHD) patients with circulatory defects. Positive effects on coronary and myocardial reserves were reported in 70,8 and 58.3%, 68,4 and 56.8% of cases, respectively. Corvaton caused side effects in 3.1%, sidnopharm in 12.5% of the patients. Corvaton is more potent as regards hemodynamics, myocardial contractility and reserves. PMID- 7985150 TI - [The use of hemosorption and plasmapheresis for treating cardiac arrhythmias (a preliminary report)]. AB - The authors present pilot experience in extracorporeal blood purification (hemosorption, plasmapheresis) aimed at correction of cardiac arrhythmia. Seven responders of 8 patients treated had less frequent episodes of cardiac fibrillation the severity of which decreased, they suffered no more from high grade extrasystoles, were put on reduced doses of antiarrhythmic drugs. The response is attributed to improvement of blood rheology and elimination of arrhythmogenic substances. PMID- 7985151 TI - [The therapeutic effect of licorice in patients with primary arterial hypotension]. PMID- 7985152 TI - [The mechanisms of the therapeutic action and the basis for the frequency of performing sessions of ultraviolet blood irradiation in treating acute pneumonia. 1]. AB - Mechanisms of therapeutic action of UV blood irradiation and optimal irradiation scheduling were studied in the course of UV-irradiated blood transfusions capable of correcting lipid peroxidation (LPO) and antioxidant system (AOS) in acute pneumonia (AP) patients. Single and multiple measurements of LPO and AOS parameters (malonic dialdehyde, diene conjugates, red cell resistance to peroxide hemolysis, catalase, superoxide dismutase, cerulloplasmin, plasma total estrogens, progesterone and testosterone) were made in 10 young males with moderate AP and 20 healthy controls. UV blood irradiation in AP is shown to be pathogenetically validated. It works via effective stabilization of LPO as a result of early adequate stimulation of endogenic AOS. Positive changes were also induced in the system of hormonal regulation. It is suggested that hyperestrogenemia plays a compensatory role in AP pathogenesis. PMID- 7985153 TI - [The relationship of the theophylline concentration in the saliva and the blood serum in patients with a broncho-obstructive syndrome]. AB - Theophylline salivary and serum concentrations (Tser and Tsal) were quantified after a single dose administration of theophylline drugs: euphylline (2.4% solution, 10 ml i.v. jet and 0.15 orally), theo-dur, retaphil, theopek, theobilong (0.3 g orally). The drugs were given to patients with broncho obstructive syndrome. The samples were obtained within 6 and 24 hours upon administration for euphylline and other drugs, respectively. Tser and Tsal were determined at high-performance liquid chromatography. The authors revealed a linear relationship between Tser and Tsal in different time intervals. The percentage factors and formulas of Tser calculation by its Tsal values have been estimated. PMID- 7985154 TI - [A comparative evaluation of the antacid properties of the preparations Maalox and Almagel]. AB - Basic modes of action and indications for aluminium and magnesium-containing antacids are reviewed. Antacid properties of Maalox were studied versus those of Almagel in 24 duodenal ulcer patients by the following indices of pH-metry: time of pH response onset, "alkaline time", alkalification area and index. All the features were significantly different when assessed in the body of the stomach. Regular Maalox intake as a main medicine provided good results in the treatment of duodenal ulcer (25 responders), gastric ulcer (14 responders), erosive gastroduodenitis (14 responders), erosive reflux-esophagitis (9 responders). Maalox displayed high symptomatic efficacy, safety, insignificant side effects. PMID- 7985155 TI - [The effect of calcium antagonists and beta-adrenoblockaders on disordered stomach functions in patients with duodenal peptic ulcer]. AB - The effect of a single dose of nifedipine or propranolol hydrochloride on gastric acid production and motility has been assessed in 90 duodenal ulcer (DU) patients having the relapse. Intragastric pH-metry showed that the drugs in a dose 20 mg significantly inhibit basal acid production. As indicated by electrogastromyography, nifedipine effect on gastric motility depends on its baseline level. The drug displays a moderate normalizing action (modulating effect) on the dominating frequency, amplitude of motor oscillations and overall capacity of gastric biopotentials. Propranolol hydrochloride noticeably lowered initially high frequency of gastric contractions. Due to nifedipine gastric evacuation inhibits and makes more regular. The authors recommend introduction of nifedipine and propranolol hydrochloride in correction of gastric dysfunction in DU patients. PMID- 7985156 TI - [Changes in the filtration function of the kidneys during the treatment of chronic glomerulonephritis]. AB - The implications of the treatment variant and chronic glomerulonephritis (CGN) characteristics in the changes of renal function were evaluated by 220 treatment courses for CGN aggravation. A number of statistical methods were employed. In CGN patients free of renal insufficiency glomerular filtration was either unaffected or recovered after transitory decline. In chronic failure further creatinine clearance diminution was observed, serum creatinine levels went up. Corticosteroid treatment was much safer for the kidneys than cytostatics. With increasing duration of CGN, functional affection of the kidney becomes more frequent irrespective of the treatment kind. The same is true for the number of exacerbation and hypertension which are also involved in renal functional decline. PMID- 7985157 TI - [Changes in the hemostatic system indices of patients with chronic kidney failure under the influence of enterosorption and plasmapheresis]. AB - A total of 83 patients with chronic renal failure (CRF) at azotemia stage (S. I. Riabov's classification) complicating pyelonephritis were treated: 19 patients received symptomatic standard therapy (group 1), 29 patients received combined therapy with enterosorption (group 2), 35 patients received combined treatment with plasmapheresis (group 3). The efficacy of the treatments was controlled by platelet tests (platelet, coagulative hemostasis, fibrinolytic plasma activity) and parameters of kallikrein-kinin system. Treatment results in group 1 are characterized as poor: insignificant improvement of uremia, DIC syndrome against unchanged inhibition of kallikrein-kinin system. Group 2 patients achieved moderate response: uremia reduced to normal azotemia values, DIC syndrome and inhibition of kallikrein-kinin system reduced. Patients of group 3 got disappeared DIC syndrome and normal kallikrein-kinin system against high azotemia. PMID- 7985158 TI - [The pharmacokinetics of recombinant human erythropoietin]. PMID- 7985159 TI - [Laser therapy in the treatment of tuberculosis of the urinary tract]. PMID- 7985160 TI - [The combined treatment of relapsing polychondritis (systemic chondromalacia) developing against a background of severe diabetes mellitus]. PMID- 7985161 TI - [The clinical efficacy of the intra- and periarticular administration of drugs with the ISI-1 jet-needle injector for treating rheumatoid arthritis]. PMID- 7985162 TI - [The optimization of Capoten treatment by taking into account its chronosensitivity in hypertension patients]. AB - The trial was made of Capoten used according to the conventional scheme (14 patients) against the drug regimen chronosensitivity-adjusted (15 patients). All the patients had essential hypertension stage II. When used at the hours of the greatest sensitivity, Capoten proved more effective this permitting lower single, daily and course doses administration, hypotensive effect occurred in shorter period of time. The effect was produced via a marked fall in peripheral vascular resistance. PMID- 7985163 TI - [Blood pressure variability (based on 24-hour monitoring data) in mild arterial hypertension]. AB - To evaluate the condition of target organs in patients with mild arterial hypertension (MAH) under normal and high arterial pressure variability (APV), the authors examined 84 MAH males aged 40-60 and 14 matched healthy controls. At 24-h monitoring it was revealed that 32% of MAH patients had high variability of daytime and night arterial pressure which occurred more frequently in atherosclerotic lesion of extracranial carotid artery portions. MAH patients with high APV against those with normal APV develop carotid artery atherosclerosis 3.5 times more frequently, vascular disorders of the fundus of the eye stage II with angiosclerosis and thickening of the interventricular septum 2.5 and 1.8 times more frequently, respectively. PMID- 7985164 TI - [The clinical trial of a Russian membrane plasma filter in patients under therapy]. AB - 35 procedures of plasmofiltration were conducted on the test series of domestic membrane plasmofilter in 25 patients suffering from atopic diseases, systemic affections of connective tissue, advanced atherosclerosis, etc. The filter proved promising in therapeutic patients. The procedure is easier to perform compared to centrifuge plasmapheresis, it can work under thin blood flow. However, centrifuge plasmapheresis has advantages over the above filtration in patients with hyperhydration, hemorrhagic syndrome, contraindications to large-dose anticoagulants. PMID- 7985165 TI - [Diaphragmatic muscle fatigue--its diagnosis and treatment]. AB - Transcutaneous stimulation electromyography of the diaphragm was performed in 64 patients suffering from chronic obstructive bronchitis (COB) to evaluate the function of the diaphragmatic muscle. Increased amplitude, area and shorter M response gave evidence for the muscle fatigue. Changes in the above parameters correlated with the degree of the respiratory insufficiency and pulmonary hypertension. The authors included subcutaneous electrostimulation of the diaphragm in combined treatment of COB patients free of clinical manifestations indicating circulation decompensation. These patients benefited from the stimulation in contrast to COB patients with decompensated circulation who failed to respond to the procedure. PMID- 7985166 TI - [The suppression of the renin-angiotensin system during the treatment of cardiovascular diseases]. PMID- 7985167 TI - [The use of beta-adrenoblockaders during and after an acute myocardial infarct]. PMID- 7985168 TI - [The use of enterosorption in IHD and lipid metabolic disorders]. PMID- 7985169 TI - [Pathogenetic approaches to the therapy of hypertension in old age]. PMID- 7985170 TI - [Gastrointestinal endoscopy and endoscopic ultrasonography in diagnosis and therapy]. PMID- 7985171 TI - [Balanced vegetarian diet is healthy]. PMID- 7985172 TI - [Data--quality--quality of data]. PMID- 7985173 TI - [Registration of activities at Norwegian anesthesia departments]. AB - Documentation and quality control of anaesthesiologic activity based on electronic data processing is less than optimal in Norwegian departments of anaesthesia. Major efforts have been made to register and store information in large data bases. It has been difficult, however, to put the collected data to practical use. The Norwegian Association of Anaesthesiologists has developed and distributed a data program, NAFREG, which is designed to take care of a minimum set of basic data to serve our needs. In order to obtain data of relevance to quality, a special code list has been developed to facilitate registration of problems related to anaesthesiologic activity. NAFREG has been in use for more than three years, and has been distributed to more than 30 hospitals in Norway. The article evaluates the registration system as practised in six hospitals participating in an evaluation project. PMID- 7985174 TI - [Colonoscopy. In investigation, treatment and control of gastrointestinal diseases]. AB - Colonoscopy is the initial examination for patients with manifest or occult rectal bleeding, inflammatory bowel disease and colorectal polyps. In addition to polypectomy, colonoscopy is useful in decompression of adynamic colonileus and laser palliation of intractable tumours. In adenoma patients controls should be limited to high risk patients, i.e. those with large and multiple tubular adenomas, villous adenomas, multiple hyperplastic polyps (> 30), and first degree relatives of patients with colorectal carcinomas. Control after radical surgical treatment of colorectal cancer is offered during the first two years after the operation and to persons younger than 40 years. The efficacy of control programmes for hereditary nonpolyposis colorectal cancer families have to be evaluated in controlled series. Rectosigmoidoscopies could probably replace some total colonoscopies to examine ulcerative colitis patients for cancer, since cancer usually occurs in the distal colon. Complications are rare after diagnostic and therapeutic colonoscopies, but perforation, bleeding and injury to surrounding organs can be experienced. PMID- 7985175 TI - [Vegetarians and vitamin B12. A controlled trial of vitamin B12 status in 63 lactovegetarians]. AB - In this study vitamin B12 status was assessed in 63 adult long-term lactovegetarians and 63 controls. No significant difference in mean plasma levels of vitamin B12 was found between the two groups. In contrast to what might have been expected, the vegetarians showed a slight increase in the vitamin B12 levels with increasing number of years as vegetarians. There was a significant (r = 0.34, p = 0.01) correlation between oral intake of vitamin B12 in the lactovegetarians and the plasma levels of the vitamin. Folate in plasma and whole blood were significantly higher (p < 0.001) in the vegetarian group than in the control group. The findings do not indicate that lactovegetarians risk developing dietary-induced vitamin B12 deficiency. PMID- 7985177 TI - [Physiotherapy in chronic obstructive pulmonary disease with and without mask training]. AB - 16 patients with chronic obstructive lung disease were randomized into two groups which were treated with physiotherapy for six weeks. In one group the treatment also involved using a respiratory training mask. Six patients in both groups completed the study. Both groups experienced an improvement for most parameters. The study showed that physiotherapeutic treatment with physical training improved the patients working capacity. However, the treatment with a mask gave no significant additional effect. 46 outpatients who were treated with a mask were asked later if they still used the mask. Only 28% used it regularly and 35% had stopped using the mask because they did not feel any effect. PMID- 7985176 TI - [Surgical treatment of cervix cancer. A 6-year material from a regional hospital]. AB - The results are reported for 75 patients treated with radical hysterectomy and pelvic lymphadenectomy (Wertheim-Meigs' operation) for cervical carcinoma. There was no per- or postoperative death. Ten patients suffered immediate postoperative complications. One case of lower limb lymphoedema was observed. 17 patients (23%) had pelvic lymph node metastases. In eight patients the disease has recurred (median observation time 43 months). Overall recurrence-free survival was 89%: for patients without lymph node metastases 91%, and for patients with metastases 82%. Using a prognostic score based on stage, presence of lymph node metastases, blood or lymph vessel invasion, low differentiation, and tumour-involved resection margins; two groups could be identified, with a recurrence-free survival of 94% (score < or = 2) and 75% (score > or = 3), respectively (p < 0.02). PMID- 7985178 TI - [Atypical sciatica. Decreasing pain and increasing paresis--a serious sign]. AB - During the last seven years 14 patients with lumbar disc hernias were admitted who presented with a short period of sciatica before experiencing relief of pain accompanied by paresis. Ten patients had marked paresis and were operated on, most of them during the first week after the start of paresis. Three patients had minor paresis in regression, and one patient suffered complete paralysis for five months. These four patients were not operated on. Motor function improved significantly in nine out of ten operated patients. Four of them had no paresis at all. The three patients with mild paresis in regression still showed some motor impairment 9-24 months later, and the condition of the patient with paralysis remained unchanged. In conclusion, patients who develop painless sciatica and marked paresis deteriorate seriously, and early surgery is necessary in order to avoid permanent disturbance of motor function. PMID- 7985179 TI - [Scleroderma with an unusual complication]. AB - A 30 year-old woman who had had progressive systemic sclerosis for seven years was admitted to our hospital with a history of one week of increasing abdominal girth and one month's history of increasing peripheral oedema, especially in the lower limbs, and a weight loss of 10 kilograms in the course of five months. On admission she had oedema of the lower limbs, lower back and abdomen, and had ascites but no signs of peritonitis. An abdominal X-ray examination revealed distended bowels with elevated air fluid levels and pneumoperitoneum. The combination of the clinical and radiological findings, as well as the history, strongly suggested a diagnosis of pneumocystosis cystoides intestinalis as a complication to progressive systemic sclerosis. The symptoms improved on treatment and no signs of recurrence were found at follow-up after four years. We discuss the underlying pathology and management of this condition. PMID- 7985180 TI - [Delirium (acute confusion) among elderly patients after admission to a medical department]. AB - Delirium is a common mental disorder among the elderly. In this study we examined the prevalence of delirium among patients older than 75 years of age who had been admitted to an acute medical ward. 14 of 58 patients (24%) received a diagnosis of delirium. For these patients we recorded in all 58 factors possibly associated with its occurrence, four on average per patient. Drugs, cerebrovascular disease, and congestive heart failure were the most common factors. The large number of possibly contributing factors precludes a definite conclusion regarding precipitating factors. Mini-Mental State Examination, which is a commonly used screening-instrument for detecting cognitive impairment, was of minor value in detecting delirium. PMID- 7985181 TI - [Endoscopic ultrasonography in the diagnosis and follow-up of gastrointestinal diseases]. AB - Endoscopic ultrasonography provides detailed images of gastrointestinal structures by means of high frequency ultrasound transducers placed within the gastrointestinal tract. In this paper, the authors describe various systems and discuss their clinical potential and indications for use. Endoscopic ultrasonography allows imaging of various small pathological lesions in the visceral wall and adjacent structures, such as the mediastinum, pancreas and distal parts of the bile duct. Experience in endoscopy and ultrasonography is necessary for a proper management of the technique. PMID- 7985182 TI - [Gastrointestinal diseases--the place of endoscopy in examination, treatment and control]. AB - Dyspepsia, defined as discomfort in the upper abdomen after a meal, is the most frequent indication for gastroscopy. Such dyspepsia was earlier considered to be an element of the ulcer disease, Moynihan's disease. Whether examination showed an ulcer or not was of minor importance as long as the treatment was the same. Similar opinions still contribute to a negative attitude towards the need to obtain a more specific diagnosis, especially in young patients where risk of cancer is low. We are of the opinion that dyspepsia is a non-specific symptom of several different diseases, and that curative therapy is often available today provided the diagnosis is correct. It is therefore necessary to make an active effort to diagnose the cause of the dyspepsia, also in younger persons. In practice, this means that there are many different indications for gastroscopy. We try, however, to practice a restrictive policy with respect to control gastroscopy. PMID- 7985183 TI - [Diagnosis and treatment with endoscopic retrograde cholangiopancreatography]. AB - Endoscopic retrograde cholangiopancreatography (ERCP) was carried out for the first time in 1968. Five years later endoscopic sphincterotomy was performed. Since then both modalities have become established as necessary adjuncts in the diagnosis and treatment of patients with pathology in the bile duct or pancreas. The main indication is common bile duct stone, and as a consequence of this treatment fewer patients are now treated surgically. Patients with malignant bile duct obstruction can be given reasonable palliation of both jaundice and pruritus and therefore improved quality of life. Some reports indicate that endoscopic drainage may be useful for pancreatic stenosis. Complications are few, but vigilance and prompt treatment is necessary to keep morbidity at a minimum. Follow-up after several years shows that sphincterotomy is successful also in the long term. The authors discuss the present diagnostic and therapeutic situation. PMID- 7985184 TI - [Night calls for general practitioners]. AB - We examined night calls in each of four rural Norwegian municipalities with 6,000 7,000 inhabitants during three months in winter 1992/1993. Most out-of-hours calls were covered by general practitioners on rota. The overall rate of night calls (2300-0700) was 55 per 1,000 inhabitants per year, varying from 39 to 77 in the municipalities (p < 0.01). In 42% of the night calls the patient was advised over the telephone, 23% were seen in the surgery and 34% were visited at home. We found a higher rate of night calls in our material than found in previous studies on the subject. We assume that this difference in the number of night calls can be explained to some extent by the different attitudes signalled by the doctors to their patient populations. PMID- 7985185 TI - [Do we endure more safety? On labor, care and changes in midwifery]. PMID- 7985186 TI - [Good improvement, health care]. PMID- 7985187 TI - [What attitude do physicians have towards risk?]. PMID- 7985189 TI - [Esophageal lesions induced by iron tablets]. PMID- 7985188 TI - [Chemical working environment among car painters in Bergen]. PMID- 7985190 TI - Bibliography of toxinology. PMID- 7985191 TI - Acute-phase response in snakebite. PMID- 7985192 TI - The epidemiology of ciguatera fish poisoning. AB - Ciguatera is a toxin-related disease caused by ingestion of a variety of toxic fish living in tropical or subtropical areas. This article aims to look at the epidemiology of the disease, from both the descriptive and analytical points of view, and to discuss them in relation to environmental aspects and socioeconomic impact. PMID- 7985193 TI - Growth inhibition of Trypanosoma cruzi and Leishmania donovani infantum by different snake venoms: preliminary identification of proteins from Cerastes cerastes venom which interact with the parasites. AB - Venom from three different snake species was tested in vitro against the protozoan parasites Trypanosoma cruzi and Leishmania donovani infantum. Two of them, Cerastes cerastes and Naja haje, exerted a significant growth inhibition of T. cruzi and L. d. infantum parasites. Heating of the venoms abolished their activity, suggesting that the active factors are thermolabile. Incubation of parasites with 125I-labelled C. cerastes venom proteins allowed preliminary identification of components which interact preferentially with the pathogens. PMID- 7985194 TI - Toxicity and carcinogenicity of riddelliine following 13 weeks of treatment to rats and mice. AB - Toxicity studies of riddelliine, a member of a class of pyrrolizidine alkaloids, were conducted because riddelliine has been found to contaminate human food sources. Groups of male and female Fischer rats were administered riddelliine by gavage in phosphate buffer at doses up to 10 mg/kg, and B6C3F1 mice at doses up to 25 mg/kg, five times a week. The animals were necropsied after 13 weeks of treatment or after a 7 or 14 week recovery period. Body weight gains were inversely related to dose in both rats and mice. Body weight of the 1.0 and 3.3 mg/kg female rats and 10.0 and 25.0 mg/kg mice remained depressed during the 14 week recovery period. At 13 weeks, significant findings included dose-related hepatopathy and intravascular macrophage accumulation in rats and hepatocytomegaly in mice. During the 14 week recovery period these lesions persisted and hepatic foci of cellular alteration in male rats and bile duct proliferation in female rats and male and female mice increased in severity. In the 10 mg/kg group of female rats adenomas of the liver occurred in two of ten at 13 weeks and in one of five at the 14 week recovery period. In separate studies, the frequency of micronucleated erythrocytes in peripheral blood was increased in male mice administered a single dose (150 mg/kg) of riddelliine. Increases in unscheduled DNA and S-phase syntheses were detected in primary hepatocytes from rats and mice treated with riddelliine at doses up to 25.0 mg/kg for 5 or 30 days. In mating trials in rats and mice, pup weights from treated dams at birth and during suckling were lower than controls. Thus, riddelliine is genotoxic and carcinogenic and may cross the placenta and/or be found in milk, causing developmental toxicity in rodents. PMID- 7985195 TI - Qualitative and quantitative determination of fluoroacetic acid in Arrabidea bilabiata and Palicourea marcgravii by 19F-NMR spectroscopy. AB - Qualitative and quantitative examination of Arrabidea bilabiata and Palicourea marcgravii by 19F-NMR spectroscopy has shown the presence of fluoroacetic acid. By acid-base enrichment it is possible to detect amounts of fluoroacetic acid which otherwise are below detection rate. The detection limit (without enrichment) is estimated to be about 4 micrograms/g. Disturbing metal ions of higher oxidation states are also removed by this way. Arrabidea bilabiata contains 64.1 micrograms/g (seeds) and 3.0 micrograms/g (leaves), and Palicourea marcgravii contains 5.4 micrograms/g (leaves). PMID- 7985196 TI - Biological properties of the venom of the Papuan black snake (Pseudechis papuanus): presence of a phospholipase A2 platelet inhibitor. AB - The whole venom of Pseudechis papuanus, in addition to its anticoagulant activity, powerfully inhibited platelet aggregation induced by ADP, adrenaline, collagen, ristocetin and thrombin. High levels of phospholipase A2 (PLA2) activity were detected. A mild procoagulant activity was also observed. Following exposure of platelets to P. papuanus venom, platelet factor 3 (procoagulant platelet phospholipid) showed decreased cofactor activity in factor X activation by Russell's viper, venom suggesting that the venom PLA2 plays a major role in the inhibition of the coagulation mechanism. In vivo rodent assays confirmed the inhibitory effect on platelets and the haemorrhagic and neurotoxic activities. It is possible that PLA2 is responsible for anticoagulation and that this, combined with the effect on platelet aggregation, a mild procoagulant and a moderately potent haemorrhagin, is responsible for the haemorrhagic diathesis observed in systemically envenomed patients. Polyvalent (Australia-Papua New Guinea) Commonwealth Serum Laboratories antivenom, currently used for clinical treatment of snakebite in Papua New Guinea, proved highly effective against P. papuanus venom in rodent and in vitro assays, despite the absence of this particular venom from the immunising mixture. PMID- 7985197 TI - Neurotoxicity and haemostatic disturbances in patients envenomed by the Papuan black snake (Pseudechis papuanus). AB - Among 335 patients presenting with snakebites in Central Province, Papua New Guinea, nine were proved by enzyme immunoassay to have been bitten by Papuan black snakes (Pseudechis papuanus). Seven showed clinical evidence of envenoming. Early symptoms included vomiting and tender local lymph nodes. Five patients had neurotoxic signs and one required mechanical ventilation. Spontaneous systemic bleeding occurred in two patients. Coagulation studies in four patients showed thrombocytopenia, prolongation of prothrombin time, mild defibrination and depletion of other clotting factors with elevated fibrin(ogen) degradation products and other evidence of fibrinolysis. One patient developed mild renal dysfunction. There was no evidence of intravascular haemolysis or rhabdomyolysis. These clinical observations, which do not distinguish victims of P. papuanus from those of taipans (Oxyuranus scutellatus canni), suggest that the venom contains neurotoxic, haemorrhagic and mild procoagulant activities. Only two other cases of proven envenoming by this species have been reported. There appears to have been a decline in the abundance of this species, and hence its medical importance, over the last 25 years. PMID- 7985198 TI - Neurotoxicity, haemostatic disturbances and haemolytic anaemia after a bite by a Tunisian saw-scaled or carpet viper (Echis 'pyramidum'-complex): failure of antivenom treatment. AB - A young man in Germany was bitten by a large captive saw-scaled viper (Echis 'pyramidum'-complex) of Tunisian origin. During the first few hours after the bite he developed evidence of disseminated intravascular coagulation and fibrinolysis, and bled spontaneously. Despite being given a total of 310 ml of three different Echis-specific antivenoms (together with large amounts of fresh frozen plasma and concentrated clotting factors), venom antigenaemia (measured by enzyme immunoassay) and coagulopathy persisted for more than 10 days, and he developed a haemolytic anaemia and mild renal dysfunction. Transient bilateral ptosis was attributed to envenoming. The venom of the snake responsible for the bite was immunologically distinct from that of Nigerian E. ocellatus and was clearly not neutralised by the three monospecific antivenoms which had been administered. This case is another illustration of the geographical variation in snake venoms and the need for pooling venoms from snakes from different parts of the geographical range in the preparation of antivenoms. Envenoming by North African Echis species may not be reversible by available antivenoms. PMID- 7985199 TI - Presence of heat-stable hemorrhagic toxins in snake venoms. AB - Twenty-eight snake venoms (seven Agkistrodon venoms, six Bothrops venoms, 13 Crotalus venoms, one Sistrurus venom, and one Bitis venom) were examined for the presence of heat-stable (100 degrees C, 5 min) hemorrhagic toxins. Both heated and unheated venoms were analyzed for their protein composition by SDS-PAGE, and tested for their hemorrhagic activity in vivo in mice and for their proteolytic activity on two different substrates. Heating all venoms led to the denaturation and loss of some proteins; however, most of the venoms retained a significant number of proteins. Seventeen venoms contained more than seven proteins after heating, whereas five venoms contained only one to three proteins. All but nine of the heated venoms had substantial hemorrhagic activity, and Agkistrodon piscivorus piscivorus venom had very high activity, almost four times that of the second most hemorrhagic venom from Crotalus viridis lutosus. Most venoms, heated or unheated, had activity on the two protease substrates. Using succinylated casein as the substrate, there was a wide range of activity, and heating drastically reduced the activity of all venoms except that of Crotalus ruber and Crotalus molossus molossus. With azocoll as substrate, all but two of the unheated venoms (Crotalus adamanteus and Crotalus viridis concolor) had very high activity, whereas upon heating, all except five venoms lost essentially all of their activity. Heated venoms from snakes in the Agkistrodon genus (except for Agkistrodon blomhoffi blomhoffi, an Asian snake) retained activity on azocoll, and this activity tended to correlate better with hemorrhagic activity of the venom than did proteolytic activity on casein. PMID- 7985200 TI - Monoclonal antibodies to VRV-PL-VIIIa, a basic multitoxic phospholipase A2 from Vipera russelli venom. AB - VRV-PL-VIIIa, the most basic phospholipase A2 (PLA2) from the venom of Vipera russelli, induces multiple toxic effects, including neurotoxicity, myotoxicity, edema and hemorrhage. Rabbit polyclonal anti-serum was raised against VRV-PL VIIIa. The antiserum cross-reacted in enzyme-linked immunosorbant assay (ELISA) with two other PLA2 from the same venom, VRV-PL-V and VRV-PL-VI, and with ammodytoxin A, caudoxin and crotoxin. Twenty-two hybridoma cell lines secreting monoclonal antibodies against VRV-PL-VIIIa were isolated. The monoclonal antibodies exhibited apparent binding affinities in ELISA with VRV-PL-VIIIa ranging over two orders of magnitude. Most of the monoclonal antibodies cross reacted moderately with VRV-PL-V and weakly with VRV-PL-VI. None of the antibodies cross-reacted with ammodytoxin, caudoxin or crotoxin. Reducing the disulfide bonds of VRV-PL-VIIIa lowered the ELISA signals of each monoclonal antibody to nonspecific levels, suggesting that all the antibodies recognize conformational epitopes. Four of the 22 antibodies neutralized the enzymatic activity of VRV-PL-VIIIa. Interestingly, two of the four exhibited the lowest affinities of the monoclonal antibody library for VRV-PL-VIIIa in ELISA, while the other two exhibited the highest. Each of the monoclonal antibodies was biotinylated and spatial binding relationships were evaluated by competition ELISA. PMID- 7985202 TI - Pathological changes induced by BaH1, a hemorrhagic proteinase isolated from Bothrops asper (Terciopelo) snake venom, on mouse capillary blood vessels. AB - The pathological changes induced in capillaries by BaH1, a hemorrhagic metalloproteinase isolated from the venom of Bothrops asper, were studied after i.m. injection in mouse gastrocnemius. Hemorrhage was observed macroscopically, and corroborated histologically, within the first 5 min. At the ultrastructural level, the earliest changes in endothelial cells, observed 1 min after toxin administration, consisted of a decrease in the number of pinocytotic vesicles, the presence of blebs and cytoplasmic projections pinching off to the vascular lumen and the detachment of endothelial cells from the surrounding basal lamina. These processes occurred concomitantly with a thinning of endothelial cells. In capillaries undergoing more advanced degenerative stages, there were gaps or breaks in endothelial cells through which erythrocytes were escaping to the extravascular space. In these cells, the basal lamina was usually absent. Throughout this process, intercellular junctions remained apparently intact and no evidence was found of extravasation through widened intercellular junctions. In addition to this morphological pattern of degeneration, some capillaries presented swollen endothelial cells with dilated endoplasmic reticulum and lacking pinocytotic vesicles. Many capillaries contained platelet plugs and fibrin. Thus, hemorrhage induced by BaH1 occurs per rhexis, as has been also described for other venoms and hemorrhagic toxins. PMID- 7985201 TI - Palytoxin-induced transmitter release in the autonomic nervous system of the rat. AB - A combination of pharmacological, histochemical, immunocytochemical, neurochemical and microscopic techniques has been used to test the hypothesis that smooth muscle contractions caused by palytoxin are primarily a response to toxin-induced release of transmitter from motor nerve terminals. In the anococcygeus, palytoxin caused a dose-dependent contraction; the dose-response curve was particularly steep in the dose range 0.3-100 nM. This part of the response was abolished by phentolamine and absent in the muscles of reserpinized animals. A single, large dose of palytoxin (100 nM) caused a biphasic contraction. Phentolamine blocked the first phase by 50% and the second by > 80%. Transmitter overflow studies showed that the toxin enhanced the release of 3H after loading with 3H-NA, and immunofluorescence showed the loss of adrenergic transmitters from the innervation. In the vas deferens, palytoxin caused a biphasic contraction of the muscle. Phentolamine blocked first phase by > 80% and the second by 47%. Immunofluorescence studies showed that stores of adrenergic transmitter were depleted but stores of NPY were not greatly affected. Indirect evidence suggested that palytoxin did not cause the release of purinergic transmitters. A direct component to the contraction was apparently present in most preparations, but though variable in extent it was usually slight. It is concluded that the contractions of smooth muscle caused by palytoxin are primarily the result of toxin-induced transmitter release. PMID- 7985203 TI - Antigenic cross-reactivity among the venoms from several species of Brazilian scorpions. AB - The venoms of seven species of scorpions living in different regions of Brazil were analysed with regard to their lethality, antigenic cross-reactivity and ability to induce antibody production. In mice, the tested scorpion venoms can be grouped as: (a) highly toxic: Tityus stigmurus Thorell (LD50 = 0.773 mg/kg), Tityus bahiensis (Perty) (LD50 = 1.062 mg/kg), Tityus serrulatus Lutz and Mello (LD50 = 1.160 mg/kg), and Tityus costatus (Karsch) (LD50 = 1.590 mg/kg); (b) moderately toxic: Tityus cambridgei Pocock (LD50 = 12.136 mg/kg); and (c) practically nontoxic: Rhopalurus agamemnon (Koch) (LD50 = 36.363 mg/kg), and Brotheas amazonicus Lourenco (LD50 = 90.909 mg/kg). On electrophoresis the venoms showed many protein bands displayed along the chromatogram, most of them cross reacting in immunoelectrophoresis and immunoblotting using horse anti-T. serrulatus, anti-T. bahiensis or anti-T. serrulatus+T. bahiensis sera as probes. The antibodies present in these antivenoms combine with venom components as measured in vitro by the ELISA assay, and neutralize their lethal effects in vivo. These results indicate that horse anti-venoms against a mixture of T. serrulatus and T. bahiensis venoms or only against T. serrulatus venom yield an antibody population able to neutralize the toxic effects found in all venoms studied. PMID- 7985205 TI - An overview of four plus decades of research in estrogens: a personal history. PMID- 7985204 TI - Scorpion sting-induced pulmonary oedema: evidence of increased alveolocapillary membrane permeability. AB - A 16-year-old boy died with acute pulmonary oedema and shock after Tityus serrulatus scorpion sting. The patient showed evidence of cardiac dysfunction and damage, an increase in tracheobronchial aspirate/plasma protein concentration, light microscopic features of the lung compatible with the adult respiratory distress syndrome and electron microscopic findings compatible with acute lung injury and increased alveolocapillary membrane permeability. PMID- 7985206 TI - Synthesis of new brassinosteroids with potential activity as antiecdysteroids. AB - The synthesis of four new brassinosteroids with 2 beta,3 beta-diol functionality and A/B cis and A/B trans ring junction is reported. These brassinosteroids could present activity as antiecdysteroids. PMID- 7985207 TI - Secretion of progesterone and 20 alpha-dihydroprogesterone during pregnancy in goats. AB - The relationships between the secretion of progesterone and 20 alpha dihydroprogesterone and the sites of their production in pregnant goats were investigated. The progesterone concentration in the peripheral plasma increased after the goats mated, and was high from day 10 to day 140 of pregnancy. The 20 alpha-dihydroprogesterone concentration increased gradually from day 0 to day 140 after mating. The progesterone concentration before parturition decreased rapidly on day 1 prepartum, but the 20 alpha-dihydroprogesterone concentration remained high until the day of parturition and then began to fall. The ratio of progesterone to 20 alpha-dihydroprogesterone decreased and fell to less than one on day 1 prepartum. The plasma concentrations of progesterone in ovarian vein and of 20 alpha-dihydroprogesterone in the ovarian vein, umbilical vein, and umbilical artery were higher than those in the jugular vein. The ratio of progesterone to 20 alpha-dihydroprogesterone in placental tissue was less than one. These results suggest that in pregnant goats the main production site is the ovary for progesterone and the ovary and feto-placental unit for 20 alpha dihydroprogesterone, and 20 alpha-dihydroprogesterone may take help to regulate progesterone production within the ovary and the feto-placental unit. PMID- 7985208 TI - Syntheses of europium-labeled digoxin derivatives and their use in time-resolved fluoroimmunoassay. AB - A simple and efficient method of derivatizing and labeling the terminal sugar ring of digoxin (and other steroid glycosides) is described. The terminal sugar ring was oxidized by periodate to dialdehyde, followed by a reaction with the aminooxy group of heterobifunctional spacer reagent. Usually, reductive amination is needed to stabilize the Schiff base-type compounds produced in reactions between amino and aldehyde groups. Here the oxime compounds produced are stable wherefore the reductive amination step can be avoided and the reaction gives high yields without significant side reactions. After characterization the digoxin dioxime derivatives formed were labeled with europium chelates. These labeled digoxin derivatives bearing one or two europium-containing chelates, coupled via different spacers, were purified and tested in a competitive time-resolved fluoroimmunoassay. Several digoxin-specific monoclonal antibodies were also tested to determine the most suitable antibody-tracer combination, which was then employed to develop a simple competitive time-resolved fluoroimmunoassay for digoxin. PMID- 7985209 TI - Synthesis of steroidal D-ring fused pyrazolines: study of regiochemistry of addition. AB - The addition of diphenylnitrilimine and C-o-chlorodiphenylnitrilimine to 3 beta hydroxyandrost-5,16-diene (3b) produced a 1/1 ratio of regioisomeric, 1,3-diaryl 2-pyrazolines (6a, 7a and 6b, 7b), whereas the addition of N-o chlorodiphenylnitrilimine gave a 5/1 ratio in favor of the [17 alpha, 16 alpha-d] regioisomer (7c). To further delineate the factors governing the regiochemistry of addition of diphenylnitrilimines to steroid 16-enes, additions were carried out on 16-acetyl-5 alpha-androst-16-ene (5b) and 1-acetylcyclopentene (10). PMID- 7985210 TI - High concentrations of conjugated bile acids inhibit bacterial growth of Clostridium perfringens and induce its extracellular cholylglycine hydrolase. AB - To investigate the effects of conjugated bile acid on bacterial growth and cholylglycine hydrolase activity, Clostridium perfringens from human feces was exposed to varying concentrations of taurine- or glycine-conjugated chenodeoxycholic acid. Extracellular enzyme activity was determined by deconjugation of radiolabeled taurocholic acid and viable cells were counted after anaerobic culture at 37 degrees C for 24 h. Viable cells were decreased with more than 1.0 mg of conjugated chenodeoxycholic acid per mL and there were no viable cells with 10.0 mg of bile acid per mL. Although total enzyme activity was decreased according to the bile acid concentration, enzyme activity per bacterium was increased between 1.0 and 4.0 mg/mL. There were no statistically significant differences between the types of conjugation. It was concluded that conjugated bile acids may exert inhibitory effect on bacterial growth and extracellular cholylglycine hydrolase activity in Clostridium perfringens. However, under the physiologic condition in the human intestine, conjugated bile acid might induce production of extracellular cholyglycine hydrolase per bacterium. PMID- 7985211 TI - Regional distribution of estradiol receptors in growing antlers. AB - This study of estrogen receptors (ER) was carried out to confirm their presence and to determine their localisation in antler bones. Partially grown antlers were amputated from red deer (Cervus elaphus) stags, the skin removed, and samples taken of periosteum, cartilaginous tissue including perichondrium, and bone. Capacity and binding of free ER in the samples were calculated by Scatchard analysis of data obtained from a radioreceptor assay which utilised [3H]estradiol as tracer. High affinity ER (ka 1.3-3.4 x 10(10)/M) were detected in all tissues sampled with the exception of bone. Receptor capacity ranged from 12-74 fmol/mg protein, ranking the tissues for capacity in the following descending order: periosteum, cartilage, calcified cartilage. These results demonstrate the presence of ER in growing antlers and indicate regional localization of the receptors within these structures. The absence of ER in bone tissue within the antler suggests that the effect of estradiol on stimulation of mineralization in this tissue is indirect and must occur via its binding to the non-calcified tissues of antlers, e.g., periosteum, perichondrium, and cartilage. PMID- 7985212 TI - 1H and 13C nuclear magnetic resonance assignments and stereochemistry of N-n butyl-N-methyl-11-(16'alpha-chloro-3',17'beta- and 17'alpha-dihydroxyestra 1',3',5'(10')-trien-7'alpha-yl) undecanamide. AB - The stereochemistry of N-n-butyl-N-methyl-11-(16'alpha-chloro-3',17'beta dihydroxyestra-1 ',3',5'(10')- trien-7'alpha-yl) undecanamide (4) and N-n-butyl-N methyl-11-(16'alpha-chloro-3',17'alpha-dihydroxyestra- 1',3',5'(10') - trien 7'alpha-yl) undecanamide (5) at the 17'-position was unambiguously established by one dimensional nuclear Overhauser enhancement (NOE difference spectroscopy). Irradiation of H-18' led to the increase in the signal of H-11'beta, H-12'beta, H 8'beta, H-15'beta, and H-16'beta for compound 4 and a very small increase in the signal of H-17' indicating the beta-orientation of the 17'-OH. In contrast, for compound 5, the increase in the signal of H-17' indicated the alpha-orientation of the 17'-hydroxy group. Complete assignment of the 1H and 13C resonances is facilitated by the following one- and two-dimensional NMR experiments: 1H homonuclear correlated spectroscopy (COSY), 1H-13C heteronuclear shift correlation (HSC), 1H-13C heteronuclear shift correlation via long range couplings (COLOC), and distortionless enhancement by polarisation transfer (DEPT). Comparison of the 1H and 13C NMR chemical shifts indicates that the stereochemistry at the 17' position is more easy to determine by analysing the chemical shifts of C-17', C-12', and C-18'. PMID- 7985213 TI - Two polyhydroxylated steroids from the Chinese soft coral Litophyton arboreum. PMID- 7985214 TI - Management of community distribution programs in Bangladesh. AB - In Bangladesh, five high- and five low-performing nongovernmental organization supported community distribution projects were studied to determine which management, supervisory, and field activities differed between the better and poorer performers. A total of 37 variables were studied, and differences between the higher- and lower-performing projects were noted for nearly all of the variables. In general, project effectiveness was associated with higher service quality, more proactive field supervision, and greater organizational clarity. No project performed all of the 37 activities well. No one or two variables predicted project success, and none of them was found to be a necessary condition for project success. Higher performance was associated with doing well on many of these variables. PMID- 7985215 TI - Misinformation, mistrust, and mistreatment: family planning among Bolivian market women. AB - Results of an ethnographic study suggest that, despite stereotypes to the contrary, urban Aymara women in Bolivia want to regulate their fertility, and sociocultural norms support fertility regulation. However, the norms also make such regulation difficult to achieve. One barrier is a deep suspicion of modern medicine and medical practitioners, who are not seen as reliable sources of information. This suspicion is reinforced when the quality of health services is inadequate. Among urban Aymara, the level of acceptability of most modern methods of contraception is low. Many would prefer to use traditional methods, even when use of these methods entails considerable sacrifice and risk of conflict with their partners, unwanted pregnancies, and recourse to unsafe abortion. PMID- 7985216 TI - Do fertility intentions predict subsequent behavior? Evidence from Peninsular Malaysia. AB - Data from the 1984 Malaysian Population and Family Survey were matched with birth registration records for 1985-87 to determine the accuracy of statements regarding desired family size that were reported in a household survey in predicting subsequent reproductive behavior. The findings of this study were that stated fertility intention provides fairly accurate forecasts of fertility behavior in the subsequent period. In other words, whether a woman has another child is predicted closely by whether she wanted an additional child. Informational, educational, and motivational activities of family planning programs would, therefore, have greater success in reducing family size if fertility intentions were taken into account. PMID- 7985217 TI - A test of alternative supervision strategies for family planning services in Guatemala. AB - This report presents results of an operations research project that tested the impact and cost-effectiveness of alternative supervision schemes of reproductive health services in Guatemala. The strategies tested were (1) indirect supervision, in which one of the two annual supervised visits to each health unit was replaced by a one-day meeting at the district level with the supervisor; and (2) self-assessment, in which one supervised visit was replaced by a two-day workshop where participants filled out self-assessment checklists identifying quality of care problems and made a plan to solve identified problems during the following months. Health units in the two experimental groups showed greater increases in productivity than units receiving traditional supervision. In both alternative strategies, supervisors were able to reach a larger proportion of health units and service providers than through the traditional supervision system. The supervised cost per unit was also lower in the two experimental groups than in the control group. Few differences were observed between the experimental and control groups in terms of the satisfaction of service providers with their jobs and of clients with services received. PMID- 7985218 TI - Abortion and women's rights in Poland, 1994. PMID- 7985219 TI - Egypt 1992: results from the demographic and health survey. PMID- 7985220 TI - Syria 1993: results from the PAPCHILD survey. Pan Arab Project of Child Development. PMID- 7985221 TI - Role of thymic stromal cells in thymocyte education: a comparitive analysis of different models. AB - The thymus is the privileged lymphoid organ for T-cell differentiation, including clonal selection. Precursor thymocytes are selected on the basis of their ability to recognize self-major histocompatibility complex molecules (MHC) that are expressed on thymic stromal cells, including epithelial cells, macrophages, and interdigitating cells/dendritic cells (IDCs/DCs). Epithelial cells have been associated with positive selection, and dendritic cells with negative selection, but the exact role played by these stromal elements is still unresolved. This review focuses on the different in vitro and in vivo approaches that have been used to elucidate the role of thymic stromal cell types in thymic function, and on a critical evaluation of these approaches. PMID- 7985222 TI - Programming for recognition and programming for response. Separate developmental subroutines in the murine thymus. AB - Pre-T cells become programmed with the capacity to make functional responses to activating stimuli in a process that occurs prior to, and independently of, T cell receptor gene rearrangement and T-cell receptor-dependent positive selection. In spite of this early programming, as differentiation proceeds further the cells enter a stage in which they appear to be unable to make any functional responses. This 'eclipse' phase begins when the cells undergo successful T-cell receptor beta-chain rearrangement and ends, with the return of their functional competence, only when they successfully traverse positive selection. These results suggest that pre-T cells are subject to two distinct subroutines of differentiation, which cannot operate at the same time: one which confers function and one which confers and selects recognition specificity. To provide a possible molecular basis for the relationship between these two processes, we consider specific alterations in response-associated transcription factors that may cause the changes in responsiveness observed during programming for recognition. The interplay of the two differentiation subroutines is proposed to be a consequence of the use of common transcription factors in different combinatorial contexts for functional responses, assembly of T-cell receptor complexes, and selection. PMID- 7985223 TI - Expression of antigens homologous to human retrovirus molecules in normal and severely atrophic thymus. AB - An immunopathologic study of normal and severely atrophic thymuses (STA) was undertaken in order to evaluate the expression of human retrovirus (envelope and core) molecules in thymic epithelial cells (TEC) in HIV negative children. Both normal and STE thymuses disclosed p19, p24, p39, p45 and p55 viral core proteins as well as gp46, gp63 glicoprotein of envelope origin. No evidence of gp160, gp120 and gp41 molecules were observed in TEC which suggested endogenous lack of receptor molecules for HIV. The results are discussed in the context of possible thymus oriented autoimmune reaction in HIV and non-HIV bearing patients and in consequence, severe injury of TEC forming microenvironment. PMID- 7985224 TI - CD8 requirements for negative selection events are directly related to the TCR antigen interaction. AB - Positive selection of class I-restricted T cells has been suggested to always require the surface expression of CD8 molecules on CD4+8+ thymocytes, whilst negative selection was found to be differentially dependent, relating to the antigen being engaged by the T cell receptor (TCR). We have studied the CD8 dependency of positive and negative selection using two TCR-transgenic (Tg) mice models, which both react against the same allo-antigen, H-2kb, back crossed with mice which are deficient for the expression of CD8. Whilst CD8 expression was always required for positive selection of cells expressing high levels of the Tg TCR, events of negative selection were differentially dependent upon CD8, reflecting the CD8-dependency of the original CTL clones. For one TCR-Tg model (derived from a CD8-dependent CTL clone), deletion of CD4+8+ thymocytes was partially dependent upon the expression of CD8, though there was still selection against Tg-TCR positive CD4+ cells, which normally exit to the periphery expressing low levels of Tg-TCR. For the other model (derived from a CD8 independent CTL clone) negative selection was unaffected by the absence of CD8. For both models the CD4-8- Tg-TCR positive population was unaffected by the absence of CD8, including, for the CD8-independent model, reduced expression of the Tg-TCR/CD3 complex. These results suggest that CD8 expression may be a prerequisite for positive selection, whilst negative selection events can occur in the absence of CD8, depending directly upon the TCR-antigen interaction. PMID- 7985225 TI - PH domain: the first anniversary. PMID- 7985226 TI - Transient intercellular adhesion: the importance of weak protein-protein interactions. AB - Intercellular adhesion is a complex phenomenon central to the development, structure and functioning of all multicellular organisms. Adhesion is mediated by distinct families of cell-adhesion molecules (CAMs), and recent studies have identified key characteristics of CAMs that influence their function. Affinity and kinetic analyses using a novel technique based on surface plasmon resonance have shown that CAM interactions that mediate transient cell adhesion may have surprisingly low affinities and extremely fast dissociation rate constants. PMID- 7985227 TI - Many an error by the same example. PMID- 7985228 TI - Protein-protein recognition mediated by a mini-protein domain: possible evolutionary significance. PMID- 7985229 TI - The biochemical basis of the regulation of smooth-muscle contraction. AB - The primary signal for smooth-muscle contraction is an increase in sarcoplasmic free Ca2+ concentration ([Ca2+]i). This triggers activation of calmodulin dependent myosin light-chain kinase, which catalyses myosin phosphorylation, thereby activating crossbridge cycling and the development of force or contraction of the muscle cell. Restoration of resting [Ca2+]i deactivates the kinase; myosin is dephosphorylated by myosin light-chain phosphatase and the muscle relaxes. Recent evidence suggests that other signal-transduction pathways can modulate the contractile state of a smooth-muscle cell by affecting specific steps in the myosin phosphorylation-dephosphorylation mechanism. PMID- 7985230 TI - The protein import machinery of the mitochondrial inner membrane. AB - Mitochondria import most of their proteins from the cytosol. Although considerable information is available on the import machineries of the mitochondrial outer membrane and matrix, until recently little was known about the machinery of the inner membrane. Recent studies have identified three mitochondrial inner membrane proteins (MIMs) as essential components of the import machinery. MIM17 and MIM23 seem to form part of a channel, while MIM44, in cooperation with the heat-shock protein Hsp70, binds the preproteins in transit. The electrical membrane potential and ATP are needed to drive protein translocation through the MIM import machinery. PMID- 7985231 TI - Nuclear protein tyrosine kinases. AB - Protein tyrosine phosphorylation plays an important role in the transduction of extracellular signals. The prototypical protein tyrosine kinases are localized at the plasma membrane and are coupled to receptors that bind extracellular factors. Thus, protein tyrosine phosphorylation was previously thought to occur only in the cytoplasm. However, several cytoplasmic tyrosine kinases have recently been found to enter the nucleus; and resident nuclear proteins, such as the catalytic subunit of RNA polymerase II, have been found to be phosphorylated on tyrosine. Nuclear tyrosine kinases may participate in the regulation of transcription, the cell cycle and possibly other nuclear processes. PMID- 7985232 TI - Proteasomes: protein degradation machines of the cell. AB - 20 S proteasomes are cylinder-shaped protein complexes that play an important role in intracellular protein degradation in eukaryotes and certain archaebacteria. Although 20 S proteasomes were first described many years ago, it has been discovered only recently that these particles can assemble with other protein complexes, presumably of regulatory function. One of the macromolecular assemblies formed, the 26 S proteasome complex, functions as an ATP-dependent protease in the ubiquitin pathway, which has been implicated in the degradation of abnormal proteins, degradation of short-lived regulatory proteins and antigen presentation. PMID- 7985233 TI - Recovering DNA from agarose gels. AB - Methods and reagents is a unique monthly column that highlights current discussions in the newsgroup bionet.molbio.methds-reagnts, available on the internet. A commonly occurring theme on the net is the recovery of DNA, and this month's column discusses the pros and cons of various methods used to extract DNA fragments directly from agarose gels. For details on how to partake in the newsgroup, see the accompanying box. PMID- 7985234 TI - Homeosis: the first 100 years. PMID- 7985235 TI - Rapid elution of DNA from agarose gels using polyester plug spin inserts (PEPSIs). PMID- 7985236 TI - Problems with ligating and cloning pYAC-RC DNA digested with SalI. PMID- 7985237 TI - Refusing the ovarian time bomb. PMID- 7985238 TI - Refusing the ovarian time bomb. PMID- 7985239 TI - Fishing for complements: finding genes by direct selection. AB - Deriving a saturated gene map of a complex genome is a daunting undertaking. By current methods, finding all the genes in even a single megabase of the human genome is technically difficult. Direct selection is a technique focussed upon the isolation of cDNAs encoded by such large genomic regions and involves hybridization-based selection and PCR methods. It is particularly useful in the positional cloning of loci associated with genetic disease and for rapidly searching large genomic regions for transcriptional units that are normally expressed at low levels. Direct selection can produce up to 100,000-fold enrichment of specific cDNAs, and allows simultaneous searches to be conducted on many complex tissues. The applications of this technique extend to many approaches that involve cDNA cloning, including isolating related genes from complex pools of cDNA. PMID- 7985240 TI - Colinearity and functional hierarchy among genes of the homeotic complexes. AB - Homeotic genes identify structures along the anterior to posterior axis during the development of most animals. These genes are clustered into complexes, and their positions within the cluster correlates with their time of expression and the positions of the anterioposterior boundaries of their expression domains. Functional analyses have revealed that this specific genetic order also coincides with a functional hierarchy among members of these complexes, so that the products of more posterior genes in the cluster tend to be prevalent over those of more anterior genes. PMID- 7985241 TI - Genetic control of host resistance to infection. AB - Human resistance to infectious diseases is often regulated by multiple genes that control different aspects of host-parasite interaction. Genetically distinct inbred strains of mice that differ in their susceptibility to specific pathogens are invaluable for dissecting such complex patterns and have allowed the identification of several host-resistance loci that regulate natural and acquired immunity in response to infection. Cloning these genes is the first step in elucidating their roles in host defense. PMID- 7985242 TI - Vg1 and regional specification in vertebrates: a new role for an old molecule. AB - The Vg1 protein was discovered some ten years ago in a screen for localized maternal RNA molecules involved in early embryonic patterning in the frog Xenopus laevis. The localization of this molecule to the vegetal pole suggested that Vg1 might function as a determinant of embryonic cell fate, and its DNA sequence revealed that it is related to factors involved in induction of the mesoderm. However, it is only in the past year that evidence hinting at the role of Vg1 in early development has emerged. It now seems that although the key component for specifying a vertebrate dorsal axis has been known to us for a decade, cryptic processing pathways have kept its role in this important process hidden from view. PMID- 7985243 TI - How flies make one equal two: dosage compensation in Drosophila. AB - Dosage compensation is the process by which the expression of X-linked genes is equalized in males and females. In Drosophila, dosage compensation occurs by coordinately upregulating the transcription rates of all the genes on the single X chromosome in males. This hypertranscription requires the functioning of four autosomal male-specific lethal (msl) genes and is under the control of the Sxl gene. Recent genetic and molecular studies have suggested that the msl proteins may associate with one another in a sex-specific heteromeric complex on the male X chromosome, where they may function to alter its chromatin structure. PMID- 7985244 TI - [What happened to the patients with dementia?]. PMID- 7985245 TI - [Colles' fracture--new therapeutic possibilities]. PMID- 7985246 TI - [Admission patterns of patients with dementia to psychiatric hospitals. A registry study over the period 1972-1988]. AB - This paper describes the admission and discharge pattern in Danish psychiatric hospitals for first-ever admitted demented patients (290, 293.09, 293.19 ICD-8) aged 65 years and over admitted in the period 1972 to 1988. The results are based on data from the Danish Psychiatric Register. The admission rate, the commitment rate and the length of stay decreased significantly from 1972 to 1988. The readmission frequency did not change during the period. A significantly increasing proportion of the patients were admitted from somatic hospitals, and there was a tendency to a higher discharge rate to somatic hospitals. Two factors may have caused the decline in admission rate, the improvement of the psychogeriatric services in the eighties and the decline in the number of psychiatric beds. The psychiatric hospitals no longer serve as nursing homes for demented patients. The results also seem to indicate that for institutional care for demented patients may have been transferred from the psychiatric hospitals to other services e.g. the somatic departments and nursing homes. PMID- 7985247 TI - [Endothelium-derived relaxing factor/nitrogen oxide. Pharmacological and clinical cardiovascular aspects]. AB - The potent vasodilator endothelium derived relaxing factor (EDRF) is released by the vascular endothelium both under basal conditions and upon stimulation by acetylcholine and other endothelium dependent vasodilators. EDRF has been identified as nitric oxide (NO) and provides communication between endothelial and smooth muscle cells in the vascular wall. Injured and/or dysfunctional endothelium as seen in a variety of cardiovascular diseases may result in decreased production of NO leading to unfavorable vasoconstriction and vasospasm whereas its overproduction may cause pathological vasodilation. Understanding the role of nitric oxide in regulation of vascular tone may facilitate novel strategies for prevention and treatment of cardiovascular disorders. PMID- 7985249 TI - [Renaissance of the reticulocyte]. AB - Flowcytometric enumeration of reticulocytes using RNA-binding fluorochromes, a method both sensitive and reproducible, is rapidly gaining ground. It performs conspicuously better than the traditional manual method of reticulocyte counting, which is unacceptably inaccurate. The reticulocyte count is a valuable indicator of erythropoietic activity, of essential importance in discerning between the aregeneratory anaemias and anaemias accompanied by an adequate, partial or complete compensatory erythropoietic response. The reticulocyte count can be applied to the monitoring of the response to treatment including both allogeneic and autologous bone marrow transplantation, as well as to the evaluation of the response to recombinant human growth factors. The mean fluorescence intensity of reticulocytes enumerated by the flowcytometric analysis, is a variable possessing an independent clinical value for calculation of a reticulocyte production index and an erythropoiesis index. PMID- 7985248 TI - [Prevention of postoperative thrombosis with low-molecular-weight heparins]. AB - To evaluate the efficacy and safety of low molecular weight heparins (LMWHs) in thromboprophylaxis, 28 orthopaedic trials and 38 trials of patients undergoing general or gynaecological surgery were studied and subjected to a partial meta analysis. In orthopaedic surgery the LMWHs were superior to placebo/dextran, and were at least as efficient as unfractionated heparin (UH) in the prevention of deep venous thrombosis (DVT). Compared with UH, one of the LMWH preparations significantly reduced the total incidence of DVT. The rate of non-fatal pulmonary embolism (PE) was 0.5% in the LMWH group and 1.2% among the controls receiving UH, dextran or vitamin K-antagonists. Seven orthopaedic patients died from PE (0.14%), none of whom received LMWH. In general surgery, the LMWHs were at least as efficient as UH with a trend towards a lower risk of pulmonary embolism. Compared with UH, LMWHs did not reduce the postoperative mortality rate, nor did they cause haemorrhage. LMWHs provide a safe and efficient prophylaxis by administration once daily. PMID- 7985251 TI - [Laparoscopically treated extrauterine pregnancy]. AB - During a period of 12 months 55 women were treated for 56 ectopic pregnancies. Forty of the 56 (71%) procedures were performed laparoscopically. The duration of operation was 74 minutes when a conservative procedure was used, and 83 minutes where a salpingectomy was performed. The median duration of a diagnostic laparoscopy followed by laparotomy in 12 women was 83 minutes. Four women (13%) had persistent trophoblast, which necessitated a second operation. Two patients had a second laparoscopy because of lower abdominal pain, but did not need further treatment. Median hospitalization time (including diagnosis and second procedures) for the laparoscopically treated women was three days (range one to 16 days). PMID- 7985250 TI - [Brachial plexus blockade via the interscalene port--for regional anesthesia/analgesia of upper extremities; use, application and risks]. AB - The interscalene technique for brachial plexus anaesthesia is described. The method is suitable for anaesthesia of the upper extremity, especially when anaesthesia of the proximal part of the arm and the shoulder region is desired. The technique is also useful in paediatric cases. Side effects are few, but the risk of paralysing of the diaphragm makes this method inappropriate for patients with severe respiratory disease. PMID- 7985252 TI - [Varicocele of the testis. A comparison between laparoscopic and conventional surgery]. AB - We compared the results of laparoscopic varicocelectomy in 11 patients with those of 11 conventional varicocelectomies. There was a significantly longer operating time for laparoscopic surgery (45 versus 35 minutes), but a shorter hospital stay (one versus two days) and a quicker return to normal activity (two versus four days). There was no statistically significant difference in the outcome of surgery in the two groups concerning symptomatology and objective findings, but three patients, all conventionally operated, had no effect of the operation. One patient, operated laparoscopically, had signs of genitofemoral nerve injury. We conclude that laparoscopic varicocelectomy may be superior to conventional surgery, but further evaluation in larger, prospective studies is warranted. PMID- 7985253 TI - [Time consumption at an orthopedic operating theatre. Physicians' ability to predict their own time consumption]. AB - The aim of the study was to investigate the time spent on different procedures in an orthopaedic operating theatre, and to evaluate the ability of doctors to predict their own time consumption. Time schedules were registered for 146 operations, of these 104 were either knee or hip replacements. Sixty percent of the total time was spent on surgery. The median misjudgment was 15 minutes for surgeons and five minutes for anaesthetists. An improvement in the doctors' ability to predict their own time consumption in the course of the study period could not be demonstrated. Comparing the study period with the similar period the year before it was not possible to demonstrate a change in the number of cancelled operations or the number of days with overtime. Epidural anaesthesia with bupivacaine was the most time consuming anaesthesia, the differences between the other forms of anaesthesia used were insignificant. PMID- 7985254 TI - [Prevention of postoperative pulmonary complications after heart-lung surgery. Comparison of 3 different mask physiotherapy regimens]. AB - The object of the investigation was to compare the effect of three different physiotherapy masks on the incidence of postoperative complications after thoracic surgery. It was carried out as a prospective, consecutive, randomized comparison at a Department of Thoracic and Heart Surgery at a University Hospital. The therapy was performed by experienced and specially trained physiotherapists. One hundred and sixty patients were evaluated; 60 patients undergoing heart surgery, 59 patients having pulmonary resection, and 41 patients with exploratory thoracotomy. In each operative category the patients were treated with one of three face mask systems used in addition to routine chest physiotherapy. These were either continuous positive airway pressure (CPAP), positive expiratory pressure (PEP), or inspiratory resistance--positive expiratory pressure (IR-PEP). Postoperative pulmonary complications were assessed by forced vital capacity (FVC), arterial oxygen tension (PaO2), and chest X-ray examination, all parameters were measured preoperatively and on the fourth and ninth postoperative day. The patients filled in a questionnaire concerning their opinions about their mask treatment. IR-PEP showed a lesser decrease in PaO2 on day nine. Otherwise there was an equal decrease in FVC and PaO2, and equal frequency of atelectasis in the three mask treatments. It is therefore concluded that any of the three therapies: continuous positive airway pressure (CPAP), positive expiratory pressure (PEP), and inspiratory resistance--positive expiratory pressure (IR-PEP) may be used as supplement to standard chest physiotherapy. PMID- 7985255 TI - [Exercise-induced asthma in children and oral terbutaline. A dose-response relationship study]. AB - We wanted to assess the protective effects on exercise-induced asthma as well as the clinical efficacy and safety of increasing doses of a new sustained-release formulation of terbutaline sulphate in 17 asthmatic children aged 6-12 years (mean 9 years). Placebo, 2, 4, and 6 mg terbutaline were given b.i.d. for 14 days in a randomized, double-blind, cross-over design. At the end of each two week period, an exercise test was performed and plasma terbutaline was measured. Compared with placebo, no significant effect was seen on asthma symptoms monitored at home, or on exercise-induced asthma. The percentage falls in FEV1 after the exercise test were 36, 35, 27 and 28%, after placebo, 4, 8 and 12 mg terbutaline/day, respectively. A small but statistically significant dose-related increase was seen in morning and evening peak expiratory flow (PEF) recordings. It is concluded that continuous treatment, even with high doses or oral terbutaline, does not offer clinically useful protection against exercise-induced asthma. PMID- 7985256 TI - [Theophylline treatment of irreversible, chronic obstructive pulmonary disease]. AB - Even though the clinical efficacy is not well established, theophylline is commonly prescribed as a second or third line drug after inhaled beta 2-agonists and corticosteroids for patients with chronic obstructive pulmonary disease (COPD). The therapeutic index is narrow, and therefore theophylline is often given in a "safe standard dose", e.g. 300 mg b.i.d. We studied the long-term effect of sustained-release theophylline 300 mg b.i.d. over four weeks in 48 patients with severe irreversible COPD (FEV1: 0.99 +/- 0.45 l, FVC: 2.21 +/- 0.68 l) in a randomized, double-blind crossover study. During theophylline treatment there was significant improvements in dyspnoea score (p < 0.001) and morning peak flow (p < 0.05). In spite of this, there was no significant change in the patients' "sense of well-being" or their daily use of inhaled beta-agonist. Spirometric tests or arterial blood gas values did not change significantly either. It is concluded that addition of theophylline in a "safe standard dose" (i.e. 300 mg b.i.d.) has only limited value in these patients. PMID- 7985257 TI - [Long-term effect of 131I therapy of multinodular non-toxic goiter]. AB - The aim of this study was to investigate the long term effect of 131I treatment on thyroid function and size in patients with non-toxic multinodular goitre. The subjects were 69 consecutive patients with multinodular non-toxic goitre selected for 131I treatment and followed for a minimum of 12 months. Outcome measures were standard thyroid function variables and ultrasonically determined thyroid volume before and after treatment. Fifty-nine patients were treated with a single dose of 131I, 12 with two doses, and one with four doses. In 45 patients treated with one dose who remained euthyroid the median thyroid volume was reduced from 73 (interquartile range 50-106) ml to 29 (interquartile range 23-48) ml at 24 months. The median reduction was 40 (22-48) ml, half of which occurred within three months. Patients treated with two doses as well as those developing hypo- or hyper-thyroidism also had a significant reduction in thyroid volume. Eleven patients developed hypothyroidism (cumulative five year risk 22%). Side effects were few. In conclusion we find that 131I treatment of multinodular non-toxic goitre is an attractive alternative to surgery. PMID- 7985258 TI - [Clinical microbiological study of sputum and aspirates from larynx or trachea. An evaluation of exact criteria for assessment by direct microscopy]. AB - A prospective study of specimens of lower airway secretions was carried out in order to investigate the association of specimen quality and results of microbiological culture. The quality of expectorates (EXP) or aspirates from larynx/trachea (ALT) was assessed on the basis of numbers per low power field (< 1, 1-10, 11-25, and > 25) of squamous epithelial cells (SEC) and leukocytes, respectively. Specimens were classified as either acceptable, A (< or = 10 SEC), partly acceptable, B (11-25 SEC, > 25 leukocytes), or not acceptable, C (the remaining specimens). Six hundred and six specimens (385 EXP, 221 ALT) from 408 patients were included, and the distribution among categories was A 373 (62%), B 88 (15%), and C 144 (24%). For isolates of Streptococcus pneumoniae (n = 42) and Haemophilus influenzae (n = 51) there was a statistically significant association with specimen quality, and for aerobic bacteria including Pseudomonas aeruginosa a trend was noted. However, isolates of Enterobacteriaceae (n = 105), Staphylococcus aureus (n = 61), yeasts (n = 45) and Branhamella catarrhalis (n = 7) were not associated with specimen quality. It is concluded that a defined set of criteria allows a useful classification of EXP and ALT by direct microscopy and that it is justifiable not to cultivate specimens found not to be acceptable (category C). PMID- 7985259 TI - [Laparoscopic varicocele surgery. A contribution to a debate on minor urological laparoscopic interventions]. AB - Results of laparoscopic varicocelectomy in three patients are presented. The indications for minor laparoscopic procedures are discussed. In order to see if laparoscopic treatment (LT) can reduce the recurrence rate, a prospective trial of LT versus the Ivanissewish method is suggested. PMID- 7985260 TI - [Unilateral ectopic twin pregnancy]. AB - A case of a 12 week unilateral ectopic twin pregnancy is presented. The condition is rare with less than one hundred reported cases. Only three reported cases of unilateral ectopic twin pregnancy have been diagnosed sonographically. In this case the diagnosis of ectopic pregnancy was made by ultrasound, but, despite the length of the pregnancy only one fetus was seen. PMID- 7985261 TI - [Bilateral iliac artery aneurysms in a Behcet-like disease]. AB - A case of bilateral iliac artery aneurysms in a 24 year old patient with a Behcet like disease is presented. Behcet's disease is characterized by multiple organ involvement. Primary manifestations are genital and oral mucosal ulcerations and eye and skin affections. Among secondary manifestations are non-specific arteritis causing thrombosis as well as aneurysmal disease of the medium-sized and large arteries. Behcet's disease should be considered in young patients with arterial aneurysms. PMID- 7985262 TI - [Congenital abnormalities--change the partner or the address]. PMID- 7985263 TI - [The number of suicides in Denmark is not increasing]. PMID- 7985264 TI - [Headache after spinal puncture]. PMID- 7985265 TI - [The choice of cannule for myelography]. PMID- 7985266 TI - [The natural P-pill]. PMID- 7985267 TI - [Late potentials after acute myocardial infarction]. PMID- 7985268 TI - [Great scientific potential in Danish registries]. PMID- 7985269 TI - [Should children on milk-free diet receive calcium supplementation?]. PMID- 7985270 TI - [Late ventricular potentials after myocardial infarction]. AB - Late potentials in the QRS complex can be detected with signal-averaged electrocardiography and are associated with delayed and disorganized ventricular activation. This article reviews the technique, describes the pathophysiological basis of late potentials, and assesses the prognostic value of late potentials for subsequent development of ventricular tachyarrhythmias and sudden cardiac death in postmyocardial infarction patients. PMID- 7985271 TI - [Acute epididymitis in boys]. AB - Acute scrotum in children frequently causes diagnostic difficulties. Instantaneous treatment is essential especially in cases of torsion of the testis. Acute epididymitis (AE) is relatively frequent also in prepubertal boys but is probably underdiagnosed. Two cases and a review of AE and the differential diagnoses towards other acute scrotal diseases are presented. It is stressed that immediate diagnosis and treatment is important, and that referral to hospital is mandatory. PMID- 7985272 TI - [Viral encephalitis after tick bite]. AB - TBE is caused by a Flavivirus and is endemic in certain areas of Central and Eastern Europe, such as Austria, the south of Germany, Hungary, Czechoslovakia, Poland, the former Yugoslavia and SNG and certain areas of Sweden and Finland. Recent developments in the Eastern European countries have made them popular with Danish travellers, who are thus exposed to infection. Until now TBE has been a very rare disease in Denmark. The clinical course is biphasic being preceded by an incubation period of ten days. After the initial phase with uncharacteristic symptoms, a period af about five days follows where the patient has no symptoms. About one-third of the patients develop meningo-encephalitis where paresis can be seen. The course of the disease is often prolonged. The prognosis is good in terms of full recovery and low mortality. The diagnosis is made serologically with haemagglutination-inhibition test or ELISA-technique. Differential diagnosis includes other causes of viral encephalitis and Lyme disease with neurological manifestations, when there is a history of tick-bites. Vaccination provides good protection and is recommended for certain travellers with trips of some duration in endemic areas. PMID- 7985273 TI - [Prehospital pain relief with nitrous oxide (Entonox)]. AB - Many patients suffering from trauma or acute illness are in need of pain treatment in the prehospital phase, a treatment they seldom receive. In Denmark, it has been considered whether ambulance personnel should be allowed to administer pain treatment. Inhalation of 50% nitrous oxide and 50% oxygen has been administered for many years by non-physicians around the world. Therefore considerations concerning implementation of this treatment in Denmark are relevant. The aim of this paper was to evaluate the available knowledge about and experiences in using nitrous oxide outside the hospital for patients suffering from acute pain. The papers so far published are positive, but give no definite background for uncritical recommendation of prehospital pain treatment with nitrous oxide. There are no controlled studies concerning the effect of pain treatment in the prehospital phase. The few available controlled studies conducted inside the hospital have not shown significant pain-relieving effects of nitrous oxide for patients suffering from pain of acute medical of surgical origin when compared to other methods of pain treatment. Controlled studies of the effects of prehospital treatment with nitrous oxide need to be done. Technical problems and problems concerning indications, side effects, complications, pollution and possible addiction remain to be fully elucidated before prehospital treatment with nitrous oxide can be recommended for routine use in the Danish ambulances. PMID- 7985274 TI - [Bone-anchored auricular prosthesis]. AB - During the period February 1989-September 1991, 15 patients with absent or defective pinna were treated with a bone-anchored auricular prosthesis at the ENT department, Rigshospitalet, Copenhagen. These patients were followed up from the hospital records and by means of a questionnaire. Altogether 40 titanium implants have been inserted, of which one implant was found not to be integrated at the time of the second-stage surgery. Five patients underwent additional surgery, one patient because of non-integration of a screw, and four patients on account of soft-tissue reactions. From the questionnaire replies it appears that all patients found the cosmetic result and the technique concerning mounting of the prosthesis very satisfactory. Nearly half the patients found that the care of the skin around the abutments caused considerable problems. Three patients had experienced unintended losses of the prosthesis. In conclusion, treatment with a bone anchored auricular prosthesis has considerable advantages compared to treatment with a prosthesis attached by adhesive. Furthermore the use of a bone anchored prosthesis should be considered a viable alternative to surgical reconstruction because of the outstanding aesthetic result and because the surgical procedure puts less strain on the patient. The disadvantage of the method is the lifelong daily care of the skin and the dependence on the health services. PMID- 7985275 TI - [Colorectal cancer in Denmark 1943-1988]. AB - Nation-wide incidence rates are presented of colorectal cancer in Denmark from 1943 to 1988. In Denmark notification of malignant and related diseases is mandatory. The percentage of histologically confirmed tumours is now 95. The annual incidence rate of colon cancer in Denmark has been increasing among men and women combined from 684 cases in 1943-1947 to 2020 cases in 1988. In the same period the incidence of rectal cancer has increased from 762 cases in 1943-1947 to 1108 cases in 1988. We analyzed the effects of age, calender time, and birth cohort with multiplicative Poisson models. We did not find consistent period effects in the models. We suggest an etiologic distinction between carcinoma of the rectum, the left colon and the right colon. PMID- 7985276 TI - [Low molecular weight heparin versus unfractionated heparin in the treatment of deep venous thrombosis--a meta-analysis]. AB - A review based on 17 randomised studies on low molecular weight heparin (LMWH) versus unfractionated heparin (UFH) in the treatment of objectively verified deep venous thrombosis (DVT) is presented. Long-term treatment with LMWH was compared with long-term UFH in two studies and with warfarin in one study. In the rest of the studies LMWH and UFH were used during initiation of oral anticoagulant therapy, and these studies were included in a meta-analysis. The relative risk of progression of DVT during LMWH treatment compared with UFH was 0.63 (95% confidence interval: 0.39-1.00) and the relative risk of major bleeding was 0.41 (95% confidence interval: 0.24-0.70). There was no significant difference in the reduction of Marder score during treatment (LMWH 5.0 versus UFH 3.8) or in the frequency of new symptomatic, scintigraphically or angiographically verified pulmonary embolism (LMWH 0.6% versus UFH 1.1%). The frequency of complications seemed independent of whether LMWH was administered once or twice daily. Monitoring of LMWH treatment is not considered necessary but determination of anti-factor Xa in plasma is recommended if bleeding occurs during treatment with LMWH. PMID- 7985277 TI - [Effect of growth hormone on sleep energy]. AB - The purpose of the study was to examine REM and delta sleep energy in adults with high and normal plasma growth hormone (GH) concentration by means of power spectrum EEG analysis. After a three-day regular sleep/waking schedule, all-night polysomnographic recordings were performed on two consecutive nights before as well as one year after treatment for acromegaly by adenomectomy. The sleep energy was calculated by power spectrum analysis. We studied nine patients aged 24-45 years with untreated active acromegaly. The same patients were re-examined one year after adenomectomy when plasma GH concentrations were normal. The acromegaly was verified biochemically by measuring basal plasma GH concentration and plasma GH during hyperglycaemia as well as insulin-like growth factor. Cerebral computer tomography (CT) and magnetic resonance (MR) scans revealed an intrasellar adenoma in all patients. The resulting sleep records obtained before and after adenomectomy were subjected to power spectrum analysis and a manually blinded sleep scoring. The power spectrum analysis showed that when circulating GH was elevated the energy in the REM sleep per minute was significantly higher compared to the REM energy/min after surgery when GH concentrations had normalized. A similar relation was found for delta sleep (stage three and four, deep sleep) where the energy per minute was higher before treatment than after. The study demonstrates that plasma GH concentration was correlated to sleep energy. During high GH concentration the REM and delta sleep energies were high and normalization of plasma GH was followed by normalization of REM and delta sleep energy per time unit. PMID- 7985278 TI - [Poisoning accidents with household chemicals among children]. AB - A review is presented of the registration of all poisoning accidents among children aged 0-6 years treated at the University Hospital, Odense, Denmark during the period 1.1.1980-31.12.1992. There were 1751 poisoning accidents of which 482 were accidents with household chemicals. There were 69 accidents with lamp oil (Petroleum) of which 67 were in the age group 0-3 years. A peak incidence in the age group 0-3 years old is seen in 1986. In 1992 the incidence is at about the same level as in 1980. The incidence in the age group 4-6 years is at almost the same level throughout the entire period. We conclude that it is necessary to continue with campaigns to prevent accidents with household chemicals among children. PMID- 7985279 TI - [Measles vaccination and age]. AB - Recent studies have found administration of high-titre measles vaccine before 9 months of age to be associated with reduced survival. Since this suggests that early immunization could be unsafe, we examined the results of immunization campaigns with Schwarz standard measles vaccine carried out in 1980-1983 in three areas of Guinea-Bissau. Children were followed to death, migration or the age of five years. Children immunized at 4-8 months of age, of whom many were later re immunized, had lower mortality between nine months and five years of age compared with children vaccinated at 9-11 months of age. The improved survival was unrelated to better protection against measles. There was no sign of socio cultural differences between children immunized at different ages. Vaccination before 9 months of age is apparently safe and it may reduce childhood mortality compared with the currently recommended strategy of immunizing from nine months of age. Randomized trials are needed to confirm these observations which may have implications for the measles immunization strategy for developing countries. PMID- 7985280 TI - [Cheese-packers' disease--respiratory complaints at a cheese-packing dairy]. AB - Twenty-one present and three former employees working in the paching room of a cheese-making dairy underwent clinical examinations including symptom history, smoking habits, chest examination, and pulmonary function tests. Blood samples were drawn to determine level of peripheral eosinophil count and antibodies to microorganisms detected by air samples. Air sample concentrations of Penicillium camemberti var. candidum, used in the cheese-production, were very high (> 6000 colony forming units per cubic metre of air). In 15 of the 24 exposed workers, precipitating antibodies towards this fungus were detected, but no antibodies were detected in a reference consisting of pooled blood from 1000 donors. Of the sixteen workers with airway symptoms five had asthma requiring treatment. Two thirds of the symptomatic cheeseworkers but only half of those without symptoms had precipitating antibodies. The high frequency of precipitating antibodies together with the clinical causes of the airway symptoms indicates an aetiological relationship between airway symptoms and heavy exposure to Penicillium camemberti. PMID- 7985281 TI - [Continuous monitoring of pulse and blood pressure among telephone operators]. AB - The purpose of the study was to evaluate a) whether the monitoring device was usable during ordinary working conditions, b) whether job-strain and self reported stress influenced the blood pressure and pulse and c) whether there was a correlation between job-strain and self-reported stress. Twenty-six female telephone-operators were monitored during a working day. Job-strain was defined as the number of calls to the telephone operator. Eighty-nine percent of the monitoring measurements were usable. No difference was found between the blood pressure and pulse during rest and during work. A significant negative correlation was found between the number of calls and the blood pressure, and a significant positive correlation between the number of calls and self-reported stress. The device can give information about variations in blood-pressure and pulse during physically quiet work. The results show surprisingly that the quantitative workload is in itself not necessarily a stress factor at work. Perhaps waiting time and unpredictability are of greater importance. PMID- 7985282 TI - [Incarceration of the ventricle through a right-sided Bochdalek hernia with symptoms of tension pneumothorax]. AB - Acute herniations through a posterolateral diaphragmatic defect (Bochdalek hernia) are rare in adults. Most of these hernias are on the left side causing gastrointestinal symptoms. We present af case of a Bochdalek hernia on the right side, where incarceration and distension of the stomach was followed by dyspnoea and haemoptysis. Aetiology, symptoms, diagnosis and treatment are discussed. PMID- 7985283 TI - [Side-effects and doping control of anabolic steroids]. AB - We present a case of a 26 year-old male body-builder who had used the anabolic steroids (AS) trenbolone and stanozolol for 10 weeks. After four weeks creatine kinase (CK) including CK-B (cardiac specific isoenzymes) levels were elevated five to ten times. He was without cardiac symptoms and electrocardiography was normal. Three weeks after he stopped using AS, CK and CK-B levels had normalized. One of the drugs, stanozolol could not be detected by the doping-control, maybe because of a fast excretion time. Sale, use and delivery of AS is prohibited in Denmark, but is used in spite of the prohibition. It is important to spread knowledge about the risks of AS among the users. PMID- 7985284 TI - [Satiation]. PMID- 7985285 TI - [Is the academic arguer a forgotten figure?]. PMID- 7985286 TI - [Women in medical research. National Institutes of Health]. PMID- 7985287 TI - [Neck pain, for the last time]. PMID- 7985288 TI - [Beta 2 agonists: were they nevertheless not dangerous?]. PMID- 7985289 TI - [The pathogenesis of vesicoureteral reflux in children (the morphological changes in the kidneys in refluxogenic nephropathy in patients with congenital and acquired vesicoureteral reflux)]. PMID- 7985290 TI - [The surgical treatment of staghorn nephrolithiasis in children and its effect on kidney function]. AB - 29 children with coral nephroliths were examined by dynamic nephroscintigraphy before surgery, after it and on postoperative month 6-24. The patients whose age ranged from 5 to 15 years underwent sectional nephrolithotomy (22 cases) or partial nephrolithotomy (7 cases). The findings led the authors to the following conclusions: the reduction in the renal function following sectional nephrolithotomy is inversely proportional to preoperative functional deficiency of the affected kidney; application of partial and sectional nephrolithotomy in children with coral and multiple nephroliths is justified only in case of contraindications to extracorporeal impulse lithotripsy; sectional nephrolithotomy in children with coral nephroliths is indicated in initial deficiency of the affected kidney function more than 50%. PMID- 7985291 TI - [The diagnosis of vesicopelvic reflux in pregnant women]. AB - The diagnosis of vesicopelvic reflux (VPR) in pregnancy is not a simple task because of the requirements of noninvasiveness, safety, minimum radiation load, informative value. The authors suggest urinalysis and ultrasound (US) investigation as VPR screening tests in pregnancy. US VPR diagnosis meets the requirements of a screening method, has the advantages of a high VPR detection capacity, noninvasiveness, feasibility of further US monitoring, simultaneous study of the urological and obstetric status. High frequency of pre- and postnatal urinary reflux, the gape of the ureteral ostia as indirect signals of VPR in pregnant patients suggest that VPR may be characteristic of pregnancy, specific "pregnancy phenomenon". The authors provide US VPR classification the stages of which are usable in VPR and its complications prophylaxis. PMID- 7985293 TI - [Current achievements in pediatric urology]. PMID- 7985292 TI - [Retrograde infusion urethrocystography in the diagnosis of urethral strictures in men]. AB - To correct urination the authors used retrograde infusion urethrocystography (RIU) in 102 males. 57 of them had an urethral stricture. A novel urethrocystography device is proposed which facilitates the procedure and is more safe in relation to complication danger. The advantages of the modified RIU over routine one are demonstrated. PMID- 7985295 TI - [The prognostic value of flow cytometry in prostatic cancer]. AB - DNA quantitation by flow cytometry was made in 36 patients with morphologically diagnosed prostatic cancer (PC) in stage II, III and IV (4, 14 and 18 patients, respectively). All the patients received adequate treatment. Aneuploid tumours were found in 25 patients (group 1), diploid ones in 11 patients (group 2). A 3 year survival in group 1 made up 65.5%, in group 2 all the patients survived 3 years. The recurrence-free survival was 22.2% and 78.8%, respectively. The above findings make it possible to regard flow cytometry DNA estimation as a reliable prognostic indication in PC. PMID- 7985294 TI - [The choice of the treatment method in kidney cancer in middle-aged and elderly patients]. AB - Long-term results of the treatment outcomes in 108 nephrectomized and 107 conservatively treated patients of presenile and senile age provided the data for the mathematical model which the authors developed for renal carcinoma survival under surgical and conservative management in the above patients. The model allows optimal case-by-case approach. The trial showed high prognostic capacity of the method. Retrospective evaluation of the treatment choice validity in 215 patients ascertained that the choice was correct only in 29.8% of the patients. For 24 patients who died early after surgery, only 20.8% of cases appeared to have the prognosis of surgery preferable. The prognostic potential of the method was tested on the control group of 60 patients. The prognosis was correct in 80% of cases. The authors hold that the proposed novel approach to therapeutic policy in renal carcinoma in pre- and senile patients may prevent unnecessary hospitalizations, decrease hospital stay duration, save medical and material resources, reduce postoperative lethality, improve treatment results. PMID- 7985296 TI - [The use of laser irradiation in nephrological practice]. AB - The authors studied therapeutic potential and mechanism of action of low intensity low-energy laser irradiating the skin at the site of the projection of the transplanted kidney poles through the development of chronic rejection or chronic pyelonephritis. The trial included 7 kidney recipients and 9 controls with primary chronic pyelonephritis. The treatment course implied 10 daily session of 20 minutes duration of He-Ne laser irradiation which was preceded by clinical-laboratory evaluation of the blood and urine, cellular and humoral immunity, hemostasis, central hemodynamics, local and mediator hormones, factors of nonspecific resistance, spin probe characteristics. The effect appeared contradictory. It is thought valid to combine quantum and drug therapy thus achieving optimal therapeutic effects and preventing side effects. PMID- 7985297 TI - [Accelerated elimination of the stone fragments after extracorporeal shockwave lithotripsy]. AB - As shown in experiments on 40 Chinchilla male rabbits, sinusoidal modulated currents (SMC) and ultrasound (US) are able to enhance bioelectrical activity of the ureteral smooth muscles. Activation of the muscular wall biopotential is followed by 0.15-0.2 s contraction. The above effect was used by the authors in rehabilitation of 120 patients after ECIL. SMC and US were included into the physiotherapeutic complex. The above patients whose concrements after the fragmentation diminished to less than 7 cm in size were divided into 2 groups. Sixty patients of group 1 received spasmolytic drugs, sodium chloride or iodine bromine baths and dynamic amplipulse therapy. Sixty patients of group 2 in addition to the above treatment were exposed to local vibration and US. All the patients were given antibacterial drugs. The percent of patients with complete urolith evacuation in group 1 amounted to 91.7%, with partial evacuation 8.3% (96.7 and 3.3% in group 2, respectively). Dynamic nephroscintigraphy demonstrated that after relevant physiotherapy renal function improved, leukocyte and red cell count in the urine and ferrum, alkaline phosphatase levels in the serum decreased. PMID- 7985298 TI - [The determination of the chemiluminescence of stimulated blood leukocytes in assessing the activity of chronic pyelonephritis]. AB - The activity of oxidant metabolism was studied in leukocytes from the whole blood of 23 patients diagnosed to have urolithiasis, chronic pyelonephritis in remission. Leukocyte function was evaluated by registration of luminol-dependent chemiluminescence. Barium sulfate microcrystals served leukocyte stimulator. Chemiluminescence was registered by chemiluminometer NPA-02. Diagnostic implication of chemiluminescence and other clinical-laboratory parameters was derived from the equations of multiple linear regression arranged in a model. It is shown possible to significantly assess chronic inflammation activity in renal tissue by whole blood chemiluminescence and ESR. Low functional activity of neutrophils recorded by chemiluminescence may indicate chronicity of renal tissue inflammation. PMID- 7985300 TI - [A ureteral papilloma on the same side as kidney aplasia]. PMID- 7985299 TI - [The evaluation of the efficacy of efferent therapy in patients with acute and chronic kidney failure by the spectrum of blood middle-molecule fractions]. AB - Blood serum endotoxins were studied in patients with acute and chronic renal failure in order to correlate this spectrum with the treatment efficacy. Gel [correction of Liquid] chromatography tests of the serum samples were made in 106 patients on hemodialysis, hemodiafiltration and hemosorption. Hemodialysis was found to significantly reduce concentration of middle-mass molecular fraction (C, D, F with molecular mass from 300 to 2000 D). Hemodiafiltration produced the same effect, but more rapidly. A single procedure of hemosorption was able to improve the patients condition in the course of 2 postprocedure weeks. The authors attribute this effect to removal of the molecular fraction A which is highly toxic. PMID- 7985301 TI - [Difficulties in the diagnosis of hormonally active tumors of the parathyroid gland]. PMID- 7985302 TI - [Percutaneous puncture diagnosis and treatment in suppurative-inflammatory lesions of the kidneys and pararenal tissues, obstructive uropathies and in kidney transplantation study]. PMID- 7985303 TI - [The role of pesticides in the occurrence of pathological changes in the kidneys]. PMID- 7985304 TI - [Acute urinary retention]. PMID- 7985305 TI - [The treatment of hydronephrosis in children]. AB - The paper presents the analysis of hydronephrosis treatment performed within 1987 1993 in 76 children. Special attention is paid to surgical techniques, methods of drainage with regard to hydronephrosis degree and pelvic contractility. The drainage system of the renal calicopelvic system using double-opening tube with continuous drop lavage is designed, the scheme of the patients' postoperative management is described. Good outcomes of pelvic electrostimulation are reported. PMID- 7985306 TI - An economic rationale for prostate cancer screening. PMID- 7985307 TI - An opportunity to determine optimal treatment of pT3 prostate cancer: the window may be closing. PMID- 7985308 TI - Children's genitourinary laparoscopic surgery: the pro side. PMID- 7985309 TI - Current thoughts on the place of laparoscopy in pediatric urology. PMID- 7985310 TI - The spectrum of acquired immune deficiency syndrome-associated testicular disorders. PMID- 7985311 TI - Hypothermia associated with percutaneous nephrolithotomy. AB - OBJECTIVES: To characterize the perioperative fall in core body temperature associated with percutaneous nephrolithotomy, and to identify patients at greater risk of hypothermia. METHODS: A retrospective review was undertaken of core body temperatures in 77 patients who underwent 95 percutaneous nephrolithotomy (PNL) procedures using room temperature irrigants over a 3 year period. Intraoperative temperature measurements were obtained via an esophageal thermistor probe. RESULTS: Mean core body temperature fell from 36.7 degrees C preoperatively to 35.8 degrees C after retrograde manipulations and subsequent patient positioning before commencing the renal puncture. The mean core temperature fell an additional mean 1.0 degrees C during the percutaneous nephrolithotomy. This additional temperature drop was proportional to the length of the procedure. Female patients had a significantly greater decline in intraoperative core body temperature than male patients (p < 0.01). Obese patients preserved their preoperative temperature more efficiently. Blood loss and advanced age had no impact on the occurrence of hypothermia. Mean preoperative temperature was regained on average within 3 hours postoperatively. CONCLUSIONS: Hypothermia occurs in the majority of patients undergoing PNL. Nearly an equivalent fall in temperature is seen during presurgical preparation, induction of anesthesia, and patient positioning as is seen during the surgical procedure itself. Efforts to preserve core body temperature both before and during the percutaneous procedure may reduce the degree of hypothermia and its potential complications. PMID- 7985312 TI - Fluorescence photodetection of neoplastic urothelial lesions following intravesical instillation of 5-aminolevulinic acid. AB - OBJECTIVES: Tiny papillary tumors and flat urothelial lesions such as dysplasia or carcinoma in situ can easily be missed during routine cystoscopy. Various methods for in vivo detection of fluorescing agents (preferentially localized in malignant tissue) have been developed. Most of them are based on systemically administered synthetic porphyrin compounds and require sensitive detection devices and image processing units for fluorescence visualization. The usefulness of intracellularly accumulated endogenous protoporphyrin IX (PPIX), induced by 5 aminolevulinic acid (ALA), for diagnosis of early bladder cancer and the correlation with cystoscopic, microscopic, and fluorescence findings was investigated. METHODS: ALA was instilled intravesically in 68 patients, followed by fluorescence cystoscopy with violet light from a krypton ion laser that produced fluorescence excitation. There were 299 biopsies obtained from fluorescing and nonfluorescing areas of the bladder. RESULTS: ALA-induced fluorescence could be easily observed with the naked eye during cystoscopy under violet light illumination. All tumor lesions were sharply marked with brightly shining red fluorescence. Correlation of fluorescence and microscopic findings gave a sensitivity of 100% and a specificity of 68.5%. There were 26 malignant or precancerous lesions that were missed during routine cystoscopy but were detected only by ALA-induced fluorescence. CONCLUSIONS: Labeling of urothelial lesions by PPIX fluorescence induced by intravesically instilled ALA seems to be a promising diagnostic procedure for malignant lesions that are difficult to visualize with standard cystoscopy. PMID- 7985313 TI - Methoxypsoralen phototherapy of transitional cell carcinoma. AB - OBJECTIVES: The goal of this research was to assess whether methoxypsoralen compounds in combination with ultraviolet light were effective in preventing cellular proliferation in an in vitro model of human transitional cell carcinoma. METHODS: Three methoxypsoralen compounds, 5-methoxypsoralen (5-MOP), 8 methoxypsoralen (8-MOP), and 4'-aminomethyl 4,5'-8'-trimethylpsoralen (AMT), were added in vitro to T-24 transitional cell carcinoma cells. Psoralens directly bind to DNA, cross-linking the strands when exposed to ultraviolet light and thereby prevent cellular division. RESULTS: In vitro activity was demonstrated utilizing AMT and ultraviolet radiation at 320 to 340 nm, preventing cellular proliferation in T-24 transitional cell carcinoma. CONCLUSIONS: Methoxypsoralen compounds in combination with ultraviolet light are effective in preventing proliferation of bladder carcinoma cells in vitro. This therapy may prove to be effective in clinical early stage transitional cell carcinoma and warrants further assessment. PMID- 7985314 TI - The optimization of laser prostatectomy. Part I: Free beam side fire coagulation. AB - OBJECTIVES: To study laser-tissue interaction and develop unifying principles for the optimization of free beam side fire neodymium:yttrium-aluminum-garnet (Nd:YAG) laser coagulation prostatectomy. METHODS: The heating patterns and coagulation volumes created by different right angle deflecting fibers were studied at different wattages and times in potato and canine models. RESULTS: In the potato, higher wattage resulted in deeper and more rapid heating. The high power density fibers created lesions of smaller volume which increased less with rising wattage than those fibers of lower power density. In the canine model, carbonization decreased heat penetration, and "popcorn" decreased superficial temperature without altering lesion size as long as it occurred without carbonization. As lasing progressed, smaller incremental increases in coagulation depth were achieved. CONCLUSIONS: To optimize coagulation laser prostatectomy, the surgeon should operate at the highest wattage which does not cause carbonization. The visualized intraoperative laser-tissue interaction allows the adjustment of laser power during the case as needed. PMID- 7985315 TI - The optimization of laser prostatectomy. Part II: Other lasing techniques. AB - OBJECTIVES: To evaluate the laser-tissue interaction during neodymium:yttrium aluminum-garnet (Nd:YAG) irradiation using right angle firing fibers in motion, contact vaporization applicators, and interstitial lightguides. METHODS: The heating patterns and coagulation volumes created during right angle firing fiber pulling and painting, contact tip vaporization, and interstitial thermotherapy were studied in potato and canine models. RESULTS: High power density right angle firing fibers can be used in motion to create coagulation lesions at 40 and 60 watts (W). The depth of such lesions was less than that obtained during fixed free beam side fire coagulation. Contact vaporization applicators caused tissue vaporization without creating concurrent coagulation lesions. Interstitial lightguide thermotherapy created coagulation lesions without carbonization using A step power reduction approach during irradiation. CONCLUSIONS: Each of the investigated methods had the ability to destroy prostate tissue, and therefore may have a role in the evolution of laser prostatectomy. PMID- 7985316 TI - Sequelae of definitive radiation therapy for prostate cancer localized to the pelvis. AB - OBJECTIVES: To evaluate sequelae and estimate quality of life utilizing a survey instrument in 133 consecutive patients who have undergone definitive radiation therapy for localized prostate cancer. METHODS: All patients reported on have been followed for 14 to 60 months (median, 31 months) after radiation therapy and only patients with definitive prostate radiation therapy are included. Of the patients still alive at time of follow-up, 115 were mailed the questionnaire. Data regarding tumor grade and stage as well as treatment were extracted from patient files. RESULTS: Of the 91% of patients who returned the questionnaire, 11% used a pad and 13% leaked more than a few drops of urine daily. Of all the respondents, 9% stated that incontinence was a problem, and 31% found urinary leaking significantly worsened after radiation therapy compared with before their diagnosis of prostate cancer. With respect to sexual function, 77% recalled being able to have full or partial erections prior to radiation therapy. At some time after radiation therapy, 22% of previously potent respondents were able to have a full erection and 41% were able to have a partial erection. Twenty-nine percent of all patients who were able to establish an erection prior to radiation therapy reported that impotence was a problem at the time of follow-up. Forty-nine percent of patients had abdominal pain, diarrhea, or abdominal cramping during or after radiation therapy and 31% of all patients still had some intestinal symptoms at the time of follow-up. Eighteen percent of all patients were significantly bothered by one or more of these bowel problems. Overall, 31% of all patients reported a persistent degree of physical discomfort that they believed was secondary to their prostate cancer or the effect of treatment. Eighty-one percent were satisfied with radiation therapy and 97% of the patients said they would have radiation therapy again if faced with the decision. CONCLUSIONS: Utilizing a sensitive questionnaire on patients who had definitive radiation therapy for prostate cancer, we found the incidence of patients bothered by incontinence to be surprisingly frequent and higher than previously reported. The frequency of impotence is similar to previous studies. However, when our incontinence and impotence data were compared to Medicare patients who had undergone radical prostatectomy, the frequencies after radiation therapy were significantly lower. Despite the rates of sequelae, the patients were generally satisfied with the decision to undergo radiation therapy and with the medical treatment received. PMID- 7985317 TI - Vesicourethral healing following radical prostatectomy: is it related to surgical approach? AB - OBJECTIVES: To explore how the occurrence of vesicourethral anastomotic strictures (bladder neck contractures [BNC]) following radical prostatectomy was dependent on these variables: postoperative urine extravasation, type of anastomosis, size of prostate, and surgical approach. METHODS: We retrospectively reviewed 143 cases over 36 months for the occurrence of early BNC (6 to 12 months follow-up). Voiding cystourethrograms (VCUC) were performed in all patients at 3 weeks. Radical retropubic prostatectomy (RRP) with direct anastomosis was performed in 93 cases, RRP and Vest anastomosis in 35 cases, and radical perineal prostatectomy (RPP) in 15 cases. RESULTS: The overall incidence of extravasation was 14.1%. Procedure-specific rates of incidence of extravasation were RPP 33.3%, RRP 18.1%, and radical retropubic with Vest anastomosis (Vest) 6.1%. Mean prostate weight was not significantly different between patients with or without extravasation. The anastomotic site was classified as being irregular (plicated) or smooth in appearance on the VCUG images. An irregular appearance was noted among 81% of the RRP, 42.4% of the Vest, and 40% of the RPP. Bladder neck contractures occurred in 29% of patients with Vest anastomosis, 14.1% with RRP, and none of the patients undergoing RPP. Only 1 patient in both the Vest and RRP group who experienced BNC was noted to have extravasation on VCUG at 3 weeks. CONCLUSIONS: We have noted that the type of anastomosis (Vest traction sutures) significantly increases the likelihood of early bladder neck contracture following radical prostatectomy. The presence of contrast extravasation on the postoperative VCUG study (implying urinary extravasation) did not influence the formation of an anastomotic stricture as long as patients were maintained with catheter drainage until resolution of extravasation. The appearance of the newly constructed bladder neck on the postoperative VCUG image was not predictive of a subsequent contracture. PMID- 7985318 TI - Incidence of external spermatic veins in patients undergoing inguinal varicocelectomy. AB - OBJECTIVES: To determine the incidence of external spermatic veins at inguinal varicocelectomy. METHODS: A prospective study was performed by making intraoperative observations on 78 varicocelectomies (47 patients) performed by a single surgeon. All patients were referred for evaluation of male infertility and had a palpable varicocele present when examined while performing a Valsalva maneuver in the upright position. Varicocelectomies were performed via the inguinal approach using x 2.5 loupe magnification. Presence of external spermatic veins was defined as visualization (with x 2.5 loupe magnification) of veins on the floor of the inguinal canal traveling posterolateral to the spermatic cord that then subsequently exited the spermatic cord before passing through the internal inguinal ring. Age, anesthetic technique, and need for incision of the external inguinal ring were also recorded for each patient. RESULTS: One third of patients had undergone left-sided varicocelectomies, while two thirds had undergone bilateral procedures. External spermatic veins were identified in 15% of left-sided varicoceles and 19% of right-sided ones. Of 31 patients undergoing bilateral varicocelectomies, 19% had at least 1 external spermatic vein. Of these patients, only 2 (7%) had a unilateral right external spermatic vein, none had a unilateral left external spermatic vein, and 4 (13%) had bilateral external spermatic veins. Overall, of all patients studied, 16% had at least 1 external spermatic vein. Follow-up at 1 year showed no evidence of clinical recurrence in any patient. CONCLUSIONS: These results emphasize the importance of distal gonadal venous anatomy in the surgeon's choice of the proper approach to varicocele repair, since external spermatic veins are only accessible via an inguinal approach. PMID- 7985319 TI - Distribution and variability of resistive index values in undilated kidneys in children. AB - OBJECTIVES: To assess better the utility of duplex Doppler sonography in the diagnosis of obstructive hydronephrosis in children, we specifically studied undilated urinary tracts with the intention of establishing a nomogram of resistive index (RI) values and determining if the RI value of 0.7 reliably precludes an undilated collecting system. METHODS: Renal duplex Doppler ultrasound was performed in a standard fashion on 47 children more than 12 months of age (93 renal units) where there was no suspicion of upper urinary tract dilation. RI and RI ratio (RIR) were calculated and statistical analysis performed. RESULTS: There were 27 males and 20 females 12 to 180 months old (mean, 63.9 months). Kidney size ranged from 5.0 to 9.8 cm (mean, 7.28 cm), RI ranged from 0.34 to 0.94 (mean, 0.65), and RIR ranged from 1.00 to 1.76 (mean, 1.14). There was no statistically significant relationship between the RI and renal size or laterality, gender, or age (p > 0.05). However, between the ages of 24 and 108 months, the RI was significantly higher in females compared with males (p = 0.002). If one were to use 0.7 and 1.10 as discriminatory values for RI, 37% of renal units had values above 0.7, and 41% of RIR values were above 1.10. CONCLUSIONS: We believe that RI values in undilated kidneys of children vary significantly and its routine use and reliability need to be evaluated further in the pediatric population. PMID- 7985321 TI - Normal and abnormal pelviscopic anatomy at the internal inguinal ring in boys and the vasal triangle. AB - OBJECTIVES: We sought to explain and define normal and abnormal laparoscopic pelvic anatomy, which has only recently become the target of much attention. METHODS: The embryology, normal anatomic landmarks, and abnormal findings of the male pelvis, as discerned from more than 350 laparoscopic investigations in boys, were analyzed. RESULTS: The medial umbilical ligament, the wishbone at the internal inguinal ring, the transverse vesical fold, and the vasal triangle are principal laparoscopic landmarks of the male pelvis. Deficient spermatic vessels, abnormal gonadal locations, patent processus vaginalis, single medial umbilical ligament, and transverse testicular ectopia were the abnormal findings. CONCLUSIONS: Laparoscopic familiarity with the male pelvis permits safe and efficient diagnostic and therapeutic navigation in this new surgical arena. PMID- 7985320 TI - Endoscopic management of bladder calculi following augmentation cystoplasty. AB - OBJECTIVES: We sought to evaluate the effectiveness and utility of an endoscopic approach to calculi that develop in the bladders of children following augmentation cystoplasty. In addition, we aimed to determine the indications for open vesicolithotomy. METHODS: We reviewed our experience between 1981 and 1993 with 26 children who formed bladder calculi following augmentation cystoplasty. Data were retrieved retrospectively with respect to management approach and outcome. RESULTS: Nineteen cases were managed cystoscopically using simple extraction and/or electrohydraulic lithotripsy; 3 cases required open vesicolithotomy and four calculi passed spontaneously. Complete stone extraction was achieved after a single endoscopic treatment in every case approached in this fashion. Every patient resumed preoperative voiding patterns and there were no infections, strictures, or other complications. Calculi reformed in 4 patients and were successfully managed endoscopically. CONCLUSIONS: An endoscopic approach to bladder calculi is a safe and effective method of managing this increasingly prevalent problem in children following augmentation cystoplasty even in the presence of a reconstructed bladder neck. Open vesicolithotomy should be reserved for the very large stone burden. PMID- 7985322 TI - Modified resectoscope loop for transurethral resection of the ejaculatory duct. AB - We report the design of a modified resectoscope loop for transurethral resection of the ejaculatory ducts. The loop is a modification of a standard 24 F resectoscope loop. Cutting dimensions are 2.5 mm in width and 3 mm in depth for the modified loop versus 6 mm in width and 5 mm in depth for the conventional loop. This modification allows precise resection of obstructed ejaculatory ducts with minimal trauma to the prostatic fossa, reducing the potential for troublesome bleeding. PMID- 7985323 TI - Congenital renal arteriovenous malformation in pregnancy presenting with hypertension. AB - Congenital renal arteriovenous malformations (AVMs) are rare, with approximately 50 cases reported in the literature. Typically, they are small (1 to 2 cm) and the majority present with hematuria and symptoms and signs of congestive heart failure. Review of the literature revealed only 4 cases reported in pregnant patients and their presentation was with hematuria and rupture of the AVM. We present a case of a young female patient with a 6 cm congenital renal AVM who was otherwise asymptomatic until her first pregnancy, when she developed and presented with symptoms of hypertension and an abdominal bruit. Her symptoms persisted postpartum. Hematuria and rupture of the AVMs were not part of her clinical course. A partial nephrectomy was curative. PMID- 7985324 TI - Percutaneous nephrolithotomy directly through an angiomyolipoma. AB - We present a patient with tuberous sclerosis and bilateral angiomyolipomas with a right partial staghorn calculi in which the calculi was managed with a percutaneous nephrolithotomy. Despite the inherent risk of hemorrhage with a percutaneous approach compounded by the fact that this was done directly through a tumor, we were able to render the patient stone free with no intraoperative bleeding, complications, or the need for postoperative blood transfusion. To our knowledge, this is the first reported case of percutaneous nephrolithotomy directly through a renal angiomyolipoma. PMID- 7985325 TI - Pudendal enterocele with bladder involvement. AB - A 72-year-old diabetic women presented with a large left labial mass following multiple prior vaginal surgeries to correct vaginal vault prolapse, including two failed right-sided sacrospinalis fixation procedures and a near total colpocleisis. After failure of conservative management, a translabial repair of this pudendal hernia containing bladder was performed. Return of the labial mass 9 months later prompted a more extensive abdominal approach. To close the defect in the urogenital diaphragm and prevent its recurrence, an absorbable mesh was used. Then, to prevent enterocele recurrence, vaginal vault suspension to the sacral promontory and closure of the Douglas pouch were performed. A review of the literature is presented, with an analysis of risk factors and corrective surgical techniques. PMID- 7985326 TI - Parapubic hernia following radical retropubic prostatectomy. AB - We report a parapubic hernia in a 54-year-old patient following radical retropubic prostatectomy. This complication can occur when the musculotendinous insertions of the rectus abdominis muscle are divided from the pubis. Bowel contents herniate over the pubic crest and can be misdiagnosed as an incisional or inguinal hernia. Successful repair depends on closure of the entire defect. Elective repair necessitates the use of prosthetic mesh. PMID- 7985328 TI - Testicular seminoma presenting with features of androgen excess. AB - A 32-year-old white man presented with worsening acne and noticeable increase in muscle bulk. On examination, a firmer area with a granular consistency was noted in the right testis. A right radical orchiectomy was performed and the histologic findings were those of a typical seminoma associated with marked Leydig cell hyperplasia. A solitary right iliac lymph node metastasis, but not the primary seminoma, contained human chorionic gonadotrophin- (HCG) producing syncytiotrophoblast, which was regarded as the hormonal stimulus for Leydig cell hyperplasia and elevated serum testosterone. This seems to be the first report of testicular seminoma presenting with symptoms of androgen excess. PMID- 7985327 TI - Metastatic malignant melanoma: an unusual case presentation. AB - Secondary involvement of the genitourinary tract with malignant melanoma is a common autopsy finding, but rarely evident clinically. We report a rare case involving a previously asymptomatic patient presenting with gross hematuria and a large renal mass, which was found to be metastatic melanoma. We propose that metastatic melanoma to the kidney, although rare, be considered in the differential diagnosis of disease processes causing hematuria. PMID- 7985329 TI - Asynchronous bilateral non-Hodgkin's lymphoma of the testis: report of three cases. AB - Asynchronous involvement of both testes by non-Hodgkin's lymphoma was observed in 3 patients ranging in age from 38 to 82 years. According to the Working Formulation, all cases were classified as large cell immunoblastic lymphomas, and immunohistochemical studies demonstrated a T-cell phenotype in 1 patient and a B cell phenotype in 2 patients. Relapse to the contralateral testis occurred after a mean interval of 6 months. The negative prognostic impact of these neoplasms is confirmed in the present series, since 2 patients died of disease 7 and 9 months after diagnosis and 1 patient had a laterocervical and Waldeyer's ring recurrence after 1 year. PMID- 7985330 TI - Treatment of urinary calculi in a porcine and canine model using the Browne Pneumatic Impactor. AB - OBJECTIVES: To define the safety and efficacy of a pneumatically driven, mechanical lithotriptor using nitinol probes through semirigid and actively deflectable, flexible fiberoptic endoscopes. METHODS: The Browne Pneumatic Impactor (BPI) uses standard compressed air to drive a nitinol wire along its long axis onto a calculus, fragmenting it. Bench top and in vivo experiments were designed to explore variables, including the effects of various nitinol probe tip designs, outer diameters, excursion distances, and sheathing materials as well as the efficiency of fragmentation with active endoscope deflection. In vivo experiments in two animal models (porcine and canine) were performed using small diameter, fiberoptic semirigid, and actively deflectable, flexible ureteroscopes. Surgically placed calculi were fragmented with the BPI and representative tissue was obtained immediately and up to 2 weeks postoperatively to define histologic changes. A panel of human urinary calculi was chosen for their relative difficulty in fragmentation with other modalities. RESULTS: Calculi, including pure calcium oxalate monohydrate, brushite, cystine, and triamterene, were fragmented with the BPI used through both semirigid and actively deflectable, flexible endoscopes. A rounded tip design and excursions of 1 mm fragmented calculi most efficiently with minimal histologic reaction. Retrograde stone migration before fragmentation was noted in dilated upper urinary tracts. This was prevented by first entrapping the calculus within a standard basket. Ureteral calculi were fragmented with the nitinol probes deflected up to 45 degrees by the flexible endoscope. With increased active deflection, the efficiency of fragmentation decreased. CONCLUSIONS: The BPI represents a safe, thermal-free endoscopic lithotrite able to fragment the hardest calculi through semirigid and flexible ureteroscopes. PMID- 7985331 TI - Role of multidrug resistance in tumors of the genitourinary tract. PMID- 7985332 TI - An unusual manifestation of malignant catarrhal fever in a yearling bull. PMID- 7985333 TI - Use of transrectal ultrasound for the detection of seminal vesiculitis in a bull. PMID- 7985334 TI - Caprine contagious agalactia caused by Mycoplasma agalactiae in the Canary Islands. PMID- 7985335 TI - Immunoglobulin concentrations in colostrum and serum of lambs of dairy sheep breeds. PMID- 7985336 TI - Slaughter of animals without pre-stunning. PMID- 7985337 TI - Slaughter of animals without pre-stunning. PMID- 7985338 TI - Eye flickering in a calf. PMID- 7985339 TI - Poultry inspection assistants. PMID- 7985340 TI - Veterinarians and zoological medicine. PMID- 7985341 TI - Prevention of the spread of porcine reproductive and respiratory syndrome virus in endemically infected pig herds by nursery depopulation. AB - An attempt was made to prevent the spread of the virus of porcine reproductive and respiratory syndrome (PRRS) on three Minnesota pig farms that had been experiencing chronic nursing pig problems, including poor growth rates and increased mortality of post weaning pigs. The PRRS virus and different bacterial pathogens were isolated from all three farms during the initial investigation, and all the farms had a high prevalence of PRRS virus-seronegative breeding animals. All the pigs tested within one week after weaning when they were 18 to 22 days old, were seronegative, whereas 80 to 100 per cent of the pigs tested at eight to nine weeks had antibody titres ranging from 1:64 to 1:1024 by an indirect fluorescent antibody method. The seroprevalence among the finishing pigs on the three farms ranged from 25 to 50 per cent. An eradication protocol was established on each farm, involving emptying the nurseries, followed by pumping out the slurry pits and cleaning, washing and disinfecting three times in 14 days. After the nurseries were repopulated there were improvements in nursery mortality and average daily weight gain, and no seropositive animals were detected in the nurseries on any of the farms; the seronegative status was maintained for the six-month testing period. PMID- 7985342 TI - An evaluation of some breeding management options in beef herds in the United Kingdom. AB - The feasibility of replacing natural service in the suckler herd with artificial breeding (artificial insemination or embryo transfer), following synchronisation of oestrus in breeding animals, was investigated. In 1991 a herd of 143 spring calving beef cows, matched for date and ease of calving, sex of calf, parity, body condition score and liveweight, were assigned to one of five controlled breeding programmes: natural service (group 1); single oestrus synchronisation using a norgestomet implant and fixed time insemination followed by natural service (group 2); double synchronisation with two consecutive norgestomet implants each with fixed-time insemination followed by natural service (group 3); synchronised as for group 2, but subjected to a movement stress two days after insemination (group 4); and cows synchronised by intravaginal progesterone/prostaglandin regimen with non-surgically transferred in vitro fertilised embryos followed by natural service (group 5). The percentage pregnancy rates to the first and second heats and overall were, respectively: group I, 55.5, 66.7 and 92.6; group 2, 44.4, 71.4 and 89.9; group 3, 52.0, 78.0 and 96.0; group 4, 55.0, 58.3 and 81.5, and group 5, 40.0, 68.2 and 85.7 per cent. In groups 2, 3, 4 and 5 the costs per pregnancy for artificial insemination or embryo transfer were 40.50 pounds, 56.62 pounds, 32.40 pounds and 149.98 pounds, respectively, and the calf weaning weights for groups 1, 2, 3, 4 and 5, adjusted for date of calving, were 250 kg, 255 kg, 252 kg, 261 kg and 259 kg, respectively. PMID- 7985343 TI - Veterinary education for wildlife conservation, health and welfare. PMID- 7985344 TI - A field study of ovine bacterial meningoencephalitis. AB - Bacterial meningoencephalitis most commonly affected lambs two to four weeks old (median three weeks, range three days to six months) with clinical signs of episcleral congestion, lack of suck reflex, weakness, altered gait and depression extending to stupor, but hyperaesthesia to auditory and tactile stimuli. Opisthotonos was observed during the agonal stages of the disease. Analysis of lumbosacral cerebrospinal fluid revealed a highly significant increase in protein concentration (P < 0.01) with a neutrophilic pleocytosis, but bacteriological culture yielded organisms in only a few cases. A response was achieved with high doses of dexamethasone and chloramphenicol in only one of 20 cases. Polyarthritis and liver abscesses in a number of lambs provided evidence of a previous bacteraemic or septicaemic episode but no definite source of the central nervous system infection was identified. In common with other infectious bacterial conditions which are prevalent during the early life of sheep, control measures should ensure an adequate transfer of passive antibody, repeated treatments of the navel, and hygienic conditions in the lambing and rearing environments. PMID- 7985345 TI - Dystrophy-like myopathy in a foal. AB - Two muscle biopsies from the gluteus medius and semitendinosus muscles of a six month-old male standardbred trotter with clinical signs of hypertrophy and hypertonicity, and an electromyogram showing myotonic discharges in the glutei, semitendinosus and semimembranosus muscles, were examined by histological, histochemical and ultrastructural methods. Histologically, the main findings were variations in fibre size and shape, vacuolisation, hyalinisation and the splitting of fibres, an increase in the numbers of internal nuclei, infiltration by connective tissue and fat, hypertrophy and the predominance of type I fibres, and clusters of one type of fibre. These histological results resembled those in human muscular dystrophy. PMID- 7985346 TI - Cold resistance of live boar spermatozoa during incubation after ejaculation. PMID- 7985347 TI - Control of venereal campylobacteriosis in a beef herd. PMID- 7985349 TI - Docking puppies' tails. PMID- 7985348 TI - Oestrus synchronisation and superovulation using equine FSH in crossbred ewes. PMID- 7985350 TI - Psittacine polyomavirus in Britain. PMID- 7985351 TI - Return to oestrus after first insemination in sow herds (incidence, seasonality, and association with reproductivity and some blood parameters). AB - As no systematic study has been done to get an accurate estimate of the incidence of return to oestrus after first insemination in sows in the Netherlands, the objectives of this investigation were: 1) to obtain an estimate of the incidence of return to oestrus after insemination at the herd level; 2) to investigate the association between incidence of return to oestrus after first insemination and reproduction characteristics in order to get an impression of the economic importance of reproductive failure. These objectives were investigated by using the reproduction results of 240 swine breeding herds in the Southern Netherlands in 1987. This information was obtained from CBK plus computerized herd management records. The average incidence rate of return to oestrus after first insemination at a herd level was 16.9 per 100 first inseminations. The occurrence of return to oestrus after first insemination was distinctly higher in the insemination months July and August compared to the rest of the year. An increased incidence, with 10 returns per 100 first inseminations corrected for confounders in a multiple linear regression model, was associated with a decrease of approximately 0.3 live born piglets/sow/year. A prospective longitudinal study was started in 1988 and 1989 in 37 sow herds. Individual sows were monitored from weaning to first insemination, to the occurrence of return to oestrus, or not, after first insemination, and to farrowing. The investigation focused in particular on the relationship between return to oestrus after first insemination and seroconversion against porcine parvovirus (PPV) and Leptospira interrogans serovar bratislava (L. bratislava).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7985352 TI - Clinical consequences of a bovine virus diarrhoea virus infection in a dairy herd: a longitudinal study. AB - The clinical consequences of infections with bovine virus diarrhoea virus (BVDV) were studied in a herd of dairy cattle, where BVDV circulated for approximately 2.5 years. Of the 136 cows that were subject to a primary infection, 129 remained healthy, 5 had mild signs, and 2 became severely ill; 1 of these 2 died from a concurrent puerperal infection. In spite of the predominantly subclinical infection, a gradual decrease of 10% or more in milk production, occurring within 10 days, was observed significantly more often in cows that seroconverted than in cows that did not seroconvert over the same period. Percentages of abortion, stillbirth, and birth of weak calves were not significantly higher in cattle that seroconverted during gestation than in cattle that did not seroconvert during gestation. Abnormal return oestruses after insemination, a possible sign of early embryonic death, and congenital abnormalities were not associated with the BVDV infection. In calves that had ingested colostrum from their seropositive dams, respiratory disease ran a significantly milder course than in calves from seronegative dams. The results indicate that, in addition to the known losses associated with the birth of persistently viraemic offspring, a 'subclinical' BVDV infection in a dairy herd may also result in substantial economic losses due to decreased milk yield and more severe respiratory disease in calves. PMID- 7985353 TI - Integrated quality control project: introduction to a farm visit protocol for growing and finishing pigs. AB - A protocol for veterinary herd-health management is proposed to support veterinary surgeons at their work with growing and finishing pig herds. The protocol is divided into preparation for the herd visit, anamnesis, selection of priority items, clinical investigation, planning, and evaluation. To prepare the visit the veterinary surgeon needs technical, medical, transport and mortality data, zootechnical observations, and clinical observations made by the farmer. From these data, monthly performance figures can be calculated. The mean of the three best monthly averages of these figures over the past 12 months can serve as target value for the herd. Recent performance figures that deviate from target values are analysed and calculated for groups of pigs in a herd. Groups can be sorted for breeding stocks, for compartments, for pens, for sex, or for age. Performance figures that deviate from target values pinpoint the main goals of the farm visit. After the anamnesis at the farm, the veterinary surgeon decides which groups of pigs have to be clinically examined. He or she then defines further steps for diagnostic research and/or treatment of herd-health problems. PMID- 7985354 TI - Integrated quality control project: relationships between pathological findings detected at the slaughterhouse and information gathered in a veterinary health scheme at pig farms. AB - In September 1986 an Integrated Quality Control Project (IQC) was started in the Netherlands. Over a period of 2 years a veterinary herd health scheme was applied to 21 growing and finishing pig herds. Information was collected concerning medical treatment, classified as group treatment and individual treatment, clinical observations, and housing factors. The main purpose of this project was to investigate relationships between pathological findings detected at the slaughterhouse and information gathered on the farm. Medical group treatments, clinical observations and housing did not reliably predict pathological findings. Individual medical treatment for respiratory disorders, started in the last 30 days before slaughter, proved to be positively related to the pathological findings 'pneumonia' and 'pleuritis' detected at the slaughterhouse. This may be useful for selecting pigs at the slaughterhouse that will require special treatment for the removal of the pleura parietalis. During the first year of the project the average daily gain (ADG) was 27.2 g. more than during the preceding 2 years (P < 0.0001). Coughing was negatively related with the ADG. More than 75 coughs per compartment during 10 minutes, recorded more than 50 days before slaughter, was positively related to a depression of the ADG (20 g; P < 0.05). Relationships between group medical treatments and ADG were statistically significant, when the group medical treatment was started more than 20 days before slaughter. Negative influences on the ADG were higher if the treatment was started closer to the slaughter date.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7985355 TI - Behavioural, household, and social problems associated with companion animals: opinions of owners and non-owners. AB - The goal of this investigation was to determine the extent to which owners of companion animals experienced problems with their animals, such as behaviour problems, and to discover their opinion about household problems such as the shedding of hairs and/or feathers. Furthermore, an attempt was made to discover the opinions of owners and non-owners about social problems such as 'companion animals make noise'. The findings are the result of a survey among 871 Dutch respondents. It was found that 43% of all companion animal owners had one or more problems with their animals. Dog and cat owners experienced many problems with the illness and the behaviour of their animals. The higher the income of the owner, the more likely he/she is to have problems with his/her animal's behaviour. Because animals with behaviour problems are a risk group, more should be done to prevent these problems. Owners of companion animals found shedding of hair or feathers the biggest disadvantage of keeping an animal. People in paid employment found cleaning the cage of the animal a bigger nuisance than did people not in paid employment. There were no differences in owner characteristics with regard to the household problems. The opinions of owners of certain species of animals, owners of other species, and non-owners about behavioural traits and the nuisance caused by that species of companion animal differed, which could lead to misunderstandings between these groups. PMID- 7985356 TI - Clustering in canine malignant lymphoma. AB - A clustering of generalized malignant lymphoma is reported in a single household of Rottweiler dogs (both parents and three of the four sibling in one litter) and in a breeding pair of unrelated Scottish terriers. In addition, malignant lymphoma of the myocardium was found in three directly related otterhounds (the sire and two sibling offspring). Possible genetic and viral factors in the aetiology of canine malignant lymphoma are discussed. PMID- 7985357 TI - Bovine leukocyte adhesion deficiency--clinical course and laboratory findings in eight affected animals. AB - The clinical course of Bovine Leukocyte Adhesion Deficiency (BLAD) in eight Holstein Friesian cattle is described. Affected animals were presented with a history of poor thriving and recurrent bacterial infections. Five of these animals had to be killed because of severe respiratory disease shortly after admittance. Three affected animals survived calfhood only as a result of frequent antibacterial treatments. At one year of age, failure to thrive and stunted growth were still evident, but infections requiring antibiotic treatments occurred only sporadically. Clinical manifestations of BLAD were found in the digestive system (gingivitis, periodontitis, alveolar periostitis, diarrhoea), the respiratory system and the skin (impaired wound healing, chronic dermatitis). A leukocytosis based on a mature neutrophilia, which persisted during infection free periods, was observed in all animals. Granulocytes were substantially deficient of beta 2-integrin expression on their membranes. Anaemia, which was noted in four animals, may be related to the Anaemia of Inflammatory Disease Complex (AID). The serum total protein content increased with time and was associated with elevated gamma-globulin levels. We suggest that, at a certain age, animals affected with BLAD are able to cope with environmental agents due to compensatory mechanisms of the immune system. PMID- 7985358 TI - Prevalence of Streptococcus bovis in racing pigeons. AB - The prevalence of S. bovis in the intestinal tract of healthy racing pigeons was determined. Crop and cloaca swab samples obtained from 810 pigeons from 14 different lofts and from 122 pigeons that were presented for routine health control were examined for the presence of S. bovis. Pooled faecal samples were also obtained from pigeons in 82 different pigeon lofts. S. bovis was isolated from crop or cloaca samples of approximately 40% of pigeons of all ages by direct culture and from 80% of the pooled faecal samples by enrichment culture. In a longitudinal study, crop and cloaca samples were collected every 3 months from pigeons in seven different pigeon lofts. The prevalence of S. bovis in these pigeons ranged from 0 to 100%. The carriage rate was not related to the season or to the age of the pigeons. The prevalence of S. bovis in organ lesions of pigeons examined at necropsy was investigated over a 35-month period. S. bovis was isolated from 10% of the birds examined. The incidence of S. bovis septicaemia was significantly higher in January to August than in September to December. It was concluded that S. bovis is an opportunistic pathogenic agent in pigeons. PMID- 7985359 TI - Determination of C-reactive protein in serum and plasma from healthy dogs and dogs with pneumonia by ELISA and slide reversed passive latex agglutination test. AB - The concentrations of C-reactive protein (CRP) in serum from dogs diagnosed as normal by clinical, haematological, and biochemical examination were determined by enzyme-linked immunosorbent assay (ELISA) and slide reversed passive latex agglutination (RPLA), using IgG antibody isolated from rabbit anti-canine CRP serum. The mean value of CRP in 66 normal dogs kept in private households was 8.4 +/- 4.9 micrograms/ml by ELISA and 8.5 +/- 6.3 micrograms/ml by RPLA. Thus, no significant difference was demonstrated between the values obtained by ELISA and RPLA. No significant age and sex-related differences were found in the CRP values. The mean concentration of CRP in 84 6-month-old Beagle dogs kept in kennels by breeders was 6.2 +/- 3.9 micrograms/ml by ELISA and 8.0 +/- 4.0 micrograms/ml by RPLA. Again no significant difference was found. The CRP values determined by ELISA and RPLA were closely correlated (r = 0.913). The serum and plasma concentrations of CRP measured by RPLA were also closely correlated (r = 0.994). This indicates that plasma can be used as well as serum to determine CRP concentrations by RPLA. PMID- 7985360 TI - Isolation and characterization of preantral follicles from foetal bovine ovaries. AB - A simple, mechanical method is described for the isolation of preantral follicles from bovine foetuses of 220-280 days of gestation. On average, 2918 + 621 (s.d.) preantral follicles were isolated per ovary. The isolated preantral follicles were characterized on the basis of the morphological appearance of the surrounding granulosa cells, the number of granulosa cell layers, and their diameter. The results show that primordial, primary, and secondary follicles differ morphologically and that they can be classified by their diameter. PMID- 7985361 TI - Productivity of trypanotolerant cattle kept under traditional management conditions in The Gambia. AB - The productivity of trypanotolerant N'Dama cattle, kept under traditional management conditions in The Gambia, West Africa, was assessed by the regular, monthly collection of health and production parameters in two study areas. The study areas were selected because of differences in tsetse challenge. Performance traits were used to build up an index to estimate the productivity of village N'Dama cattle. The productivity index per 100 kg cow maintained per year varied from 37.2 kg in the study area of Keneba village (with a low tstse challenge) to 21.4 kg for cattle kept near the villages of Tuba and Sambelkunda, an area which had a high tsetse challenge. Average age at first calving was 4.5 or 5.0 years depending on the study area, calving intervals were 623 or 703 days and there was an average 12% loss of body weight in adult females during the dry season. The productivity indices of village N'Dama cattle in The Gambia compare favourably with similar indices for trypanotolerant and trypanosusceptible breeds elsewhere in Africa, and show that even under harsh conditions and with high tsetse challenge, they are able to effectively produce milk and meat for the rural population. PMID- 7985362 TI - Chemiluminescence properties of porcine pulmonary alveolar macrophages and polymorphonuclear cells. AB - A luminol-enhanced chemiluminescence (CL) technique was developed for porcine pulmonary alveolar macrophages (PAM) and polymorphonuclear cells (PMN). PAM were obtained from lung washings of 3 week old gnotobiotic pigs. PMN were obtained from peripheral blood by separation on a discontinuous Percoll gradient. Optimum CL signals were obtained with 10(5) PAM/tube and 5 x 10(4) PMN/tube. Stimulation indexes (SI) for PAM were approximately 10 for phorbol myristate acetate (PMA), 8 for opsonized Actinobacillus pleuropneumoniae and 3 for opsonized zymosan. SI for PMN varied from 100 to 180 for complement opsonized zymosan, from 50 to 100 for opsonized A. pleuropneumoniae and from 10 to 20 for PMA. Formyl-methionyl phenylalanine and calcium ionophore A23187 did not stimulate the oxidative activity of PAM or PMN. PAM that had been frozen and stored in liquid nitrogen reacted as freshly obtained PAM in the CL assay; however, PMN that had been frozen lost a great deal of their ability to produce oxygen radicals after thawing. The CL technique offers new perspectives for the study of immune mechanisms in swine. PMID- 7985363 TI - Pharmacokinetics and bioavailability of folic acid and plasma levels of bioactive folates after folic acid administration to pigs. AB - After intravenous (1 mg/kg body weight), intramuscular (1 mg/kg body weight) and oral (1 and 50 mg/kg body weight) administration of folic acid (FA) to pigs, plasma levels of FA, tetrahydrofolic acid (THF), 5-methyltetrahydrofolic acid (5MF) were determined by using high-performance liquid chromatography. The pharmacokinetic profile of plasma FA after oral administration indicated an absorption rate-limited elimination, i.e., so called 'flip-flop' phenomenon. The bioavailability of FA was quite low after a high oral dose (F = 0.01), in contrast to a high value after intramuscular administration (F = 0.95). The plasma levels of biologically active, reduced forms of folates (THF and 5MF) were significantly increased over their basal levels after IV and IM administration to FA. The levels of these active folates were not increased after oral administration of a similar dose of FA. A 50 times higher dose was required to increase the active folates to the levels observed after IV and IM administration. PMID- 7985364 TI - PRRS: effect on herd performance after initial infection and risk analysis. AB - In early 1991, the Dutch pig industry was struck by Porcine Reproductive and Respiratory Syndrome (PRRS). Data from 91 breeding and/or farrow to finish herds that were positive for PRRS were used to investigate the impact of PRRS on productivity and to evaluate the relationship between PRRS and farm and management factors. The farms involved used the CBK management information system. Results show that herd performance was severely affected by PRRS over a period of 4-6 months. A rough economic evaluation, using a fixed price for piglets, indicated that the economic loss on the 91 farms averaged Hfl. 215,- (= 65 pounds) per sow per year due to a decreased number of piglets raised per sow per litter, a prolonged farrowing interval and a higher replacement rate of sows. The analysis of possible risk factors did not reveal major factors that could be helpful in reducing the negative effect of PRRS on Piglets Reared per Sow per Year and on the Economic Index of farms experiencing an outbreak of PRRS. PMID- 7985365 TI - [Diagnostic value of ultrasonographic evaluation of thoracic and cervical organs in lymphogranulomatosis and lymphosarcoma]. AB - Examinations of 65 patients with Hodgkin's disease (n = 61) and with non Hodgkin's (n = 4) by x-ray method, computer-aided tomography, and sonography were carried out and the potentialities of sonography in detection of the lymph node lesions in lymph collectors above the level of the diaphragm analyzed. Sonography helped detect signs of envolopment of small palpated and nonpalpated lymph nodes, differentiate individual nodes, conglomerations, specify the volume an localization of changes in the mediastinal lymph nodes and in the adjacent anatomical structures, and choose an approach to collection of material for morphologic examination. Ultrasonic examination is informative as a method for monitoring the treatment results and for disease recurrences during the period of postirradiation changes in the mediastinum. PMID- 7985366 TI - [Computed tomography in the diagnosis of abdominal and retroperitoneal lymphosarcomas]. AB - Analysis of the data of 87 computer-aided tomographic examinations of patients with peritoneal and retroperitoneal lymphosarcomas permitted the authors single out a peculiar computer-tomographic "semeiotics" of this condition. Four states in computer-tomographic changes of the lymph nodes in this area were distinguished, each of them corresponding to specific clinical manifestations of the suffering. The authors came to such a conclusion as a result of detecting in the same 18 patients of a clear-cut correlation between the type of computer tomographic semeiotics and lymphosarcoma phase in the process of therapy and after it, during remission. Not denying a high value of computer-aided tomography in the diagnosis of peritoneal and retroperitoneal lymphosarcomas, the authors confirm the well-known diagnostic potentialities of ultrasonic examination and consider that ultrasound should remain the primary diagnostic instrument in such conditions. PMID- 7985367 TI - [Magnetic resonance tomography and magnetic resonance angiography in the clinical diagnosis of extra- and intracranial arterial pathology in patients with arterial hypertensions]. AB - The authors analyze diagnostic potentialities of magnetic resonance (MR) angiography of the extra- and intracranial arteries in healthy volunteers and patients with arterial hypertension of various origins and course. Fifteen healthy subjects aged 18 to 40 and 33 patients with arterial hypertension were examined; 13 of these patients presented with essential hypertension, eleven with that combined with extracranial arteries atherosclerosis, and nine with nonspecific aortoartheritic. The most informative images were those of extra- and intracranial arteries in three-dimensional reconstruction making use of programs with a decreased magnetization vector angle and a short TR period when the vessel was characterized by a high intensity of the signal against the background of low intensive adjacent tissues. MR angiography provides diagnostically reliable information on the status of extra- and intracranial arteries, permits imaging of vascular stenoses and occlusions, as well as of aneurysms and arteriovenous malformations. Analysis of MR angiographic and tomographic data permits a sufficiently accurate assessment of the relationships between MR tomographic picture of the brain and changes in extra- and intracranial arteries. MR angiography extends the potentialities of other MR tomographic methods in assessment of changes in small vessels and helps in a number of cases reduce the number of invasive interventions in examination of a patient. PMID- 7985368 TI - [First clinical experience of radio-endovascular functional thyroidectomy in the treatment of diffuse toxic goiter]. AB - To suppress Thyroid pathologic activity in diffuse toxic goitre the authors have for the first time resorted to roentgenoendovascular functional thyroiedctomy. This method consists in vascular isolation of the thyroid by superselective catheterization of the left and right thyroid arteries followed by their material occlusion. For embolization a wide spectrum of nonlyzed synthetic, organic, and inorganic materials were used. The operation was carried out in 32 patients with stages III-IV diffuse toxic gotre. The advantages of this technique over subtotal thyroidectomy are emphasized. A stable clinical and hormonal remission and reduction of thyroid size to first degree were observed in all the patients for more tham 1.5 years after roentgenoendovascular intervention. PMID- 7985369 TI - [Radiodiagnosis of tooth diseases, periodontosis and parodontosis (lecture)]. PMID- 7985370 TI - [Vacuum cassette for radiography and its possibilities]. AB - A new x-ray vacuum universal cassette is described. The basic technologic parameters of image quality obtained with this cassette are described as is the cassette design. The informative value of images obtained with vacuum and common mechanical cassettes is compared. Technologic parameters of the quality of all types of Russian commercial amplifying screens are presented and the types of screens distinguished preferable for use with vacuum cassettes. PMID- 7985371 TI - [Trends in the development of radiologic equipment and technology]. PMID- 7985372 TI - [Bronchogenic cyst of atypical localization in a 10 year old child]. PMID- 7985373 TI - [A case of infiltrative lipoma of retroperitoneal space]. PMID- 7985374 TI - [Good is changing to the best]. PMID- 7985375 TI - [Interventional radiology today and tomorrow]. PMID- 7985376 TI - Isolation, characterization and protection studies in mice of a streptomycin dependent mutant of Streptococcus suis type 1/2. AB - An avirulent, streptomycin-dependent (Str-D) mutant of Streptococcus suis type 1/2 was produced and characterized by its antimicrobial susceptibility, growth kinetics, biochemical reactions and reversion rate. Homologous and heterologous vaccine trials in mice resulted in complete protection against challenge with S. suis types 1 and 1/2 and partial protection against challenge with S. suis type 2. PMID- 7985377 TI - Estimation of the genome size of five strains of Taylorella equigenitalis isolated in Japan. PMID- 7985378 TI - Aldrin epoxidase and 7-ethoxyresorufin-O-deethylase (EROD) activity in livers from lambs of three different breeds of Norwegian sheep. AB - The concentration of aldrin epoxidase was significantly greater in the livers of Norwegian Pelt lambs than in those of Rygja lambs but did not differ significantly between either of these two breeds and Spael lambs. Conversely, although there was no detectable EROD activity in the livers of many of the lambs in all three breeds, the median activity was greater in the livers of Rygja lambs than was the case for Spael lambs. PMID- 7985379 TI - Impaired local deiodination of thyroxine to triiodothyronine in dogs with symmetrical truncal alopecia. AB - Thyroid dysfunction causes certain dermatological alterations in dogs. Insufficient delivery of thyroid hormone to the skin may originate not only from inadequate thyroid function but also from impaired local activation of thyroxine in the target organ. Thyroid parameters and deiodination were investigated in healthy dogs (group C) and in dogs with cutaneous lesions associated with hypothyroidism (group H) or with a low-T3 syndrome (group LT). The ability of the skin to convert T4 to T3 was impaired in both groups H and LT but not in the controls. It is concluded that impaired local deiodination may contribute to skin problems in dogs. PMID- 7985380 TI - Sterol composition in polyene antibiotic-sensitive and resistant strains of Malassezia pachydermatis. AB - The membrane sterol compositions of ten strains of Malassezia pachydermatis were analysed by gas-liquid chromatography. Six of these were wild-type strains from clinical sources that were sensitive to polyene antibiotics, whereas the other four strains were resistant mutants that had arisen after treatment with N-methyl N'-nitrosoguanidine or UV radiation. The wild-type strains contained 838.8 to 1291.7 micrograms of sterol per gram of freeze-dried mycelium. The sterols were composed of 79% ergosterol, 19% fecosterol and 2% lichesterol. The mutant strains contained 277.1 to 348.8 micrograms/g of sterols composed of 76% ergosterol and 24% fecosterol. PMID- 7985381 TI - Safety of the attenuated anticoccidial vaccine 'Paracox' in broiler chickens isolated from extraneous coccidial infection. AB - A trial was carried out in 1-day-old broiler chicks raised for 54 days in floorpens under simulated commercial conditions, but isolated from all extraneous virulent coccidial infections, to demonstrate the safety of 'Paracox' attenuated vaccine administered at the recommended dose when chicks were 7 days old. The vaccine did not adversely affect the water consumption, faecal moisture or litter condition of the broilers. Recycling of the attenuated coccidia occurred in vaccinated birds, oocysts being present in the litter between 5 and 33 days after vaccination; a single peak of oocysts was detectable 5 or 12 days after vaccination. Unvaccinated medicated control birds did not produce oocysts, indicating freedom from both between-pen contamination by the vaccine and invasion of the chicken-house by extraneous coccidial infection. A small proportion (4%) of vaccinated birds had mild coccidial lesions when sampled at 26, 33 or 40 days after vaccination. Despite this, the vaccinated birds performed better than control (unvaccinated, nicarbazin-treated) birds and there was no post-vaccinal check in their weight gain. Their mean finishing weight was 10.4% greater, their food conversion ratio 7.2% lower and their mortality 44.4% lower than the unvaccinated control birds, reflecting the safety of 'Paracox' vaccine. PMID- 7985382 TI - Cholinergic activity of intestinal muscle in vitro taken from horses with and without equine grass sickness. AB - Equine grass sickness (EGS) is a pan-dysautonomia of horses that involves central and peripheral neuronal degeneration and ultimately depletion. This is the first reported functional study on the motility of equine intestine taken immediately post mortem from horses with EGS. Strips of smooth muscle from the small intestine of healthy and EGS-affected horses were suspended in an organ bath and their motility was measured isometrically. The activity of the cholinergic system was studied. Physostigmine enhanced the motility of all muscle strips. Tissues taken from horses suffering from acute grass sickness (AGS) had the longest latency before a measurable response could be obtained (p < 0.05). The ileum appeared to be damaged by EGS to a greater extent than the duodenum. For the duodenal strips the enhanced rate of spontaneous contractions was significant (p < 0.05) for both normal tissue and that affected by grass sickness but this was not the case for the ileal strips. Muscarinic receptor sensitivity investigation using bethanecol suggested a hypersensitivity of receptors with AGS material. PMID- 7985383 TI - Comparative pharmacokinetics of fenbendazole in buffalo and cattle. AB - Swamp buffalo (Bubalus bubalis) and Droughtmaster cattle (Bos indicus x B. taurus), fitted with gastrointestinal cannulae, were dosed intraruminally with fenbendazole at 7.5 mg/kg liveweight, together with a chromium oxide capsule and a pulse dose of NaCoEDTA, to estimate the flow dynamics of the digesta in the rumen and duodenum. The concentrations of fenbendazole (FBZ) metabolites were measured in plasma and duodenal fluid collected over 120 h. In plasma, significantly lower peak concentrations and earlier disappearance of FBZ and its sulphoxide (OFZ) metabolite were observed in buffalo, which considerably reduced systemic availability in comparison with cattle. The availability of OFZ in the duodenal fluid of buffalo was significantly lower, whereas FBZ disposition was similar to that in cattle. The turnover rate of fluid in the rumen was higher in buffalo than in cattle, while the flow parameters for other digesta were similar in the two species. It is concluded that the decreased absorption of drug in buffalo was attributable to the shorter residence time of the dose in the rumen, and probably in the entire gastrointestinal tract. This may reduce the efficacy of treatment and indicate the need for higher dose rates for benzimidazole anthelmintics in buffalo than in cattle. PMID- 7985386 TI - [13th Austrian Geriatrics Congress on Healthy Aging. Bad Hofgastein, 19-25 March 1994. Abstracts]. PMID- 7985384 TI - Preliminary observations on the effects of meloxicam in a new model for acute intra-articular inflammation in dogs. AB - The effects of intra-articular injection, on two occasions, 3 weeks apart, of the contrast agent Urografin on the cytological and biochemical characteristics of synovial fluid (SF) were examined in two studies in dogs. The first study provided baseline data in two non-medicated dogs. The second study used a cross over design whereby 4 dogs received a 7-day oral treatment with either a placebo or meloxicam (0.2 mg/kg body weight daily) with a washout period of 3 weeks, in order to determine the effect of this new non-steroidal anti-inflammatory drug (NSAID) on the response to Urografin injection. SF samples were collected under general anaesthesia prior to and at 24 and 72 h after each Urografin injection. The volume, relative viscosity, white blood cell count and concentrations of protein, lactate dehydrogenase (LDH) and hyaluronic acid of these samples were determined. The results from both studies indicate that intra-articular injection of Urografin provoked a mild local transient inflammatory response, the most dramatic evidence of which was an increase in the white blood cell count in the SF after 24 h. In the second study, comparison of the synovial fluid measurements of the placebo-treated dogs at 24 h after Urografin injection with those prior to injection revealed significant increases in SF volume, white blood cell count, protein concentration and LDH activity and a significant reduction in relative viscosity. At 72 h after injection, only the white blood cell count and relative viscosity were significantly different from the pre-injection values.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7985385 TI - Electrophysiological characteristics of tension receptors in the abomasal antrum of sheep. AB - Unitary impulse activity from tension receptors in the abomasal antrum in sheep anaesthetized with chloralose was studied with concurrent measurements of isometric tension in the antral wall, intraluminal pressures and electromyography (EMG). Rhythmical background activity had a close correlation with intraluminal pressure changes and usually a close correlation with local increases in EMG activity and isometric tension. Impulse frequencies increased, but were not sustained, following changes from isotonic to isometric conditions. Tension receptors were excited by transmural compression, by antral distension and by local intra-arterial injections of acetylcholine (2.5-25 micrograms), pentagastrin (10-20 micrograms), 5-hydroxytryptamine (1-20 micrograms), adrenaline (10 micrograms) cholecystokinin-8 (1-5 micrograms) or bradykinin (0.5 20 micrograms), and by systemic injections of bethanecol (5-1000 micrograms). Local intra-arterial perfusions of atropine (50 micrograms) and hexamethonium (100 micrograms) did not abolish spontaneous antral movements or affect the enhanced impulse activity evoked by acetylcholine or 5-hydroxytryptamine. Most antral tension receptors were excited by increases in antral tension or passive distension; they therefore functioned 'in series' with the muscularis externa. The discharges of three tension receptors were 'off-loaded' early during the contraction evoked by local injections of pentagastrin (10-20 micrograms). PMID- 7985387 TI - Adrenal hyperechogenicity in hemolytic uremic syndrome. AB - Hemolytic uremic syndrome is characterized by an abrupt onset of a microangiopathy, thrombocytopenia, hemolytic anemia and renal failure. These abnormalities present in varying degrees. The vascular abnormalities include endothelial swelling and thrombus formation. The kidney is the major target of involvement, although intestines, lung and brain may also be affected. It is considered a disease of the infant, although it occurs in older children and adults as a component of thrombotic thrombocytopenic purpura. We present the sonographic findings of adrenal involvement in a child with hemolytic uremic syndrome, which seems to be a rare occurrence. The patient developed adrenal insufficiency during the acute phase of the disease. PMID- 7985388 TI - Pedal radiocolloid lymphoscintigraphy in demonstration of a post-surgical lymphatic leak. AB - Radiocolloid lymphoscintigraphy is a very effective diagnostic procedure for dynamic evaluation of lymphatic flow. In this case report, the use of radiocolloid lymphoscintigraphy in detection of a post-surgical lymphatic leak is presented. Dynamic pedal lymphoscintigraphy with Tc 99m-antimony trisulfide colloid clearly demonstrated the site of the leak. PMID- 7985389 TI - Issues of domestic violence unique to rural areas. AB - Domestic violence against women occurs within and across all socioeconomic, demographic, and geographic regions of the United States. Many of the dynamics related to domestic violence, and which trap women in violent relationships, also cross these boundaries. These dynamics include societal and community attitudes toward violence, isolation, fear of exposure, lack of resources to facilitate leaving a violent relationship, and lack of sufficient accessible services for victims of violence. This paper highlights that these and other issues of domestic violence are intensified in rural settings. As such, physicians working in rural areas may face unique challenges in helping battered women. Such challenges will require solutions based on knowledge of specific rural location. A number of rural-based solutions for physician interventions with rural battered women are discussed. PMID- 7985390 TI - In situ breast cancer: a local area analysis of Dane County, Wisconsin. PMID- 7985391 TI - In situ breast cancer correlates with mammography use, Wisconsin: 1980-1992. PMID- 7985393 TI - [Diagnosis and therapy of osteoid osteoma of the vertebral lamina--a literature review and personal experiences]. AB - Osteoid-osteoma is a benign tumor which is rarely situated in the spine. Five patients with osteoid-osteoma of the lamina treated surgically at the Department of Orthopaedic Surgery of the University of Mainz between november 1990 and january 1992 are reviewed. The combination of pain, painful reactive scoliotic position of the spine or torticollis, hot spot in scintigraphy and nidus in computer tomography is the typical feature of the tumor. The average delay between the onset of symptoms and definitive diagnosis was 10 months. In all cases the tumor was completely removed. In one case with localization in the axis in a 15 year old boy a laminoplastic was performed. The average follow-up was 16 months. Surgical treatment afforded immediate relief of pain and an early return to full spinal mobility. In case of persisting backache especially in children or young adults osteoid-osteoma of the spine must be suspected. The scintigraphy represents the most sensitive method of diagnosis in the early stage. PMID- 7985392 TI - [Malformations of the human tail bud or: caudal agenesis syndrome. A review]. AB - This study presents radiological and clinical findings in 70 patients with aplasia of caudal spinal segments and associated anomalies of the lower extremities and the inner organs. From a functional point of view 5 different types can be classified--unilateral hemi-aplasia, bilateral aplasia with or without sacral plateau, complex malformations of the caudal spine and medial spinal aplasia. Foot deformities and anomalies of the inner organs are common findings regardless to the extent of spinal aplasia, whereas popliteal webbing is only seen in cases with involvement of the lumbar spine. The lack of osseous junction between the spine and the pelvis leeds to a lumbopelvic kyphosis. Additionally the iliac wings are rotated in the frontal plane with the result of a narrow pelvic outlet and a change in the geometry of the hip joints. Embryologically all types of caudal spinal aplasia can be referred to a damage of the human tail bud. However, the term "Syndrome of Caudal Regression" is misleading; with respect to the presented results it is proposed to call this type of spinal malformation "Syndrome of Caudal Aplasia". PMID- 7985394 TI - [Course and prognosis of congenital scoliosis]. AB - 75 patients (33 male, 42 female) with congenital scoliosis, diagnosed first time between birth and 40 years were examined. Type and site of the anomaly were classified and evaluated in accordance with a standardized scheme. The prognosis of congenital scoliosis depends strongly on the type of the anomaly. The differences of progression in the site of the abnormality are therefore minor. Unilateral unsegmented bars showed the most severe progression: the yearly rate of deterioration of the curve averages 7.6 degrees. Unilateral hemivertebrae showed 1.5 degrees (upper thoracic region) and 2.3 degrees (lower thoracic region). Two contralateral hemivertebraes and block vertebraes had a yearly rate of deterioration less than 1 degree. Operation is the treatment of choice in case of unilateral unsegmented bars. A conservative treatment is sufficient in most cases of other abnormalities. PMID- 7985395 TI - [Value of imaging techniques in the diagnosis of lumbar intervertebral disk prolapse]. AB - As a seeming law of nature the possibility of making use of various multiplanar sectional imaging techniques is accompanied by diagnostic exaggeration. Simple and cost effective procedures with low radiation dosage such as plain x-rays of the spine are being thrust into the background. Not seldom are patients referred to the spine surgeon with MRI or Cat scan at hand but lacking standard radiographs. As far as the assessment of intervertebral disc disease is concerned the combination of plain X-rays of the spine and computed tomography of the level in question turned out to be sufficient for indication of the operation in more than 90% of 450 patients after nucleotomie at the Orthopedic University Clinic Mainz. To our mind MRI should be restricted to cases in whom disc surgery had failed to relieve sciatica. Here it allows to distinguish between a recurrent HNP and postoperative scar tissue. In our patients myelography, an invasive procedure, has its role only in emergency diagnostics, and in the dynamic functional examination. PMID- 7985396 TI - [Multi-segmental fusion of scoliosis in Duchenne's muscular dystrophy]. AB - Operations in scoliosis in patients suffering from an advanced stage of Duchenne muscular dystrophy are associated with a higher risk due to the extent of the curves, the respiratory insufficiency and frequent cardiomyopathia. Progressive scolioses in 20 wheelchair patients with an age between 10.5-18.3 years (mean 14.6 years) were treated by CDI. The mean preoperative angle in this group was 70.6 degrees, the postoperative angle 31.2 degrees (mean correction 39.4 degrees or 55.8%). The preoperative lordosis of the lumbar spine (mean angle 4.1 degrees) was corrected to 17.8 degrees postoperatively. The average intraoperative blood loss (2300 ccm) was evident more compared with idiopathic scoliosis. One neurologic complication (postoperative disturbance of bladder function) was observed. Nowadays early surgical correction and stabilization (Cobb angle > 20 degrees) has to be recommended as the treatment of choice for scolioses in Duchenne muscular dystrophy using multisegmental instrumentation methods to enable rapid mobilisation and a postoperative care without brace or cast. This conception allows a prophylactic operation including the following targets: prolongation of life expectancy, improvement of sitting position and prevention of rapid deterioration of lung function including assisted mechanical ventilation in late stages. PMID- 7985397 TI - [Augmentation of VDS (ventral derotation spondylodesis) using double rod instrumentation: surgical method and early results]. AB - INTRODUCTION AND AIM OF THE STUDY: The advantages of the VDS according to Zielke with excellent three dimensional correction and shorter fusion levels in comparison to posterior instrumentation techniques are well known. A disadvantage is the postoperatively necessary long immobilisation in a body cast due to lack of primary stability. Aim of the presented double-rod-VDS is to optimize the system by augmentation and allow a postoperative plaster cast- and brace-free treatment. METHOD AND MATERIAL: Following thoracolumbar phrenotomy and ligation of the segmental vessels Kaneda-clamps are inserted. First VDS-screws are implanted into the posterior holes of these clamps. Using a M-4 compression rod, correction is obtained by centripetal compressive forces to the nuts. Next VDS screws for the M-5 treated rod are inserted into the anterior holes of the Kaneda clamps. The rod is implanted in a slightly compressive manner and augments the system. Within a prospective study 12 patients with idiopathic and neuromuscular scoliosis underwent this surgical procedure. Three patients with thoracolumbar scoliosis have been followed for 12 months postoperatively and are presented as case reports. All patients were treated brace-free postoperatively, only using a semi-elastic vest for 4 months. RESULTS: Remarkable intra- and postoperative complications have not been noted. Curve correction ranged from 75 to 86%. Implant related complications and loss of correction have not been noted so far. The sagittal plane was within physiological limits postoperatively. Scanning stereography demonstrated excellent three dimensional correction. CONCLUSION: The results of the Double-rod-VDS allow the statement, that the advantages of the VDS according to Zielke are optimized by augmentation of the system with the possibility of plaster cast and brace-free postoperative treatment. Larger operation numbers and a longer follow-up period are needed for further assessment. PMID- 7985399 TI - [Atlas fractures with paralysis of the caudal cranial nerves. A case report]. AB - The fracture of the Atlas is a serious trauma, associated with important diagnostic traps. Whether operative or noninvasive treatment should be used depends on the type of fracture. Paralysis of brain nerves are exceptionally rare. We present a case in which fracture of the atlas was associated with paralysis of the 9th through 12th brain nerves, to which differential diagnostic considerations are discussed. PMID- 7985398 TI - [Spastic paraparesis in Scheuermann disease: a case report]. AB - A case of paraparesis due to Scheuermann's disease in a 17.5 years old boy suffering from a moderate dorsal kyphosis (Cobb angle 64 degrees) is reported. Etiologically, spastic paraparesis can be caused either by myelon compression due to extradural cysts, herniated dorsal discs, or direct myelon compression from the vertebral bodies. Radiologically, in addition an intraspinal lipom was suspected. Because of the neurological deficits surgical treatment was performed. Ventral release followed by an anterior spondylodesis was combined with a dorsal spondylodesis using the Harrington compression system. An intraspinal lipom could be excluded intraoperatively after laminectomy of the suspicious region. Three months postoperatively, no signs of any neurological deficits were observable. X ray control demonstrated a solid spondylodesis with an Cobb angle of 38 degrees. Direct myelon compression or indirect myelon damage due to a reduced blood supply at the apex of kyphosis are supposed to be the pathophysiological pathway. PMID- 7985401 TI - [The distribution of cartilage degeneration of the human patella in relation to individual subchondral mineralization]. AB - According to Pauwels and Kummer the distribution of the subchondral mineralisation can be taken as a measure of the long-term mechanical loading in the joints. Based on a previous study concerning the density distribution of the subchondral bone of the human patella, these results were compared in the following paper with the macroscopically visible cartilage lesions. Degenerative changes on the lateral facet of the patella coincide with regions of high bone mineralisation, those on the "odd facet" on the other hand with areas of low subchondral density. The cartilage lesions on the lateral facet are seen as being due to high and constant mechanical stress, those on the "odd facet" to short infrequent stress-peaks. PMID- 7985400 TI - [A new plate for dorsal occipito-cervical fusion. Design, surgical technique, initial clinical results]. AB - A survey of actually practiced methods for cranio-cervical fusion is presented, followed by the description of a new osteosynthesis-plate to solidly fuse this region. The new plate offers a number of advantages when compared with competing procedures. It is rigidly fixed to the occipital bone by five screws, sublaminar wireloops bond the vertebrae to be fused to both branches of the U-shaped plate where the individual loops are positioned into obliquely ascending slots. This safely prevents migration and disengagement resulting in a high initial horizontal and vertical stability allowing for a postoperative care without external support. During the procedure tightening of the wire loops may succeed on reposition of the deformity. The plate exists in two lengths allowing fusion of C0-C2 or more segments of the cervical spine. The typical indication is instability of C0-C2 in rheumatoid arthritis or tumoral lesions of the area. Clinical experience in 7 patients suffering from rheumatoid arthritis (follow-up: 6-31 months) is very positive, fusion has occurred in all cases. PMID- 7985402 TI - [Results in patello-femoral joint replacement in various knee endoprostheses (Type GSB and ES)]. AB - 105 patients with 137 total knee replacements (105 model GSB, 32 model ES) were reexamined 4.3 years (2 to 9.7 years) postoperatively. 63.9 percent suffered from chronic polyarthritis. The clinical result (Insall 100-point score) averaged 73.6 points (78.2 ES-, 71.7 GSB II-knees). In 28.6 percent of the GSB- and 3.1 percent of the ES-knees osteolyses of the patella were apparent. Subluxation or complete dislocation of the patella was present in 85.7 percent of the GSB- and 25 percent of the ES-knees. The result was dependent on the preoperative knee axis, patellar height and the implant site of the tibial component. Revisions with complete removal of the inlay were most successful. PMID- 7985403 TI - [Treatment of foot deformities in diastrophic dysplasia--a case report]. AB - We report the follow-up of a neonate with Pes equinovarus et adductus due to diastrophic dysplasia. The feet have been treated operatively by lengthening of the calcaneal tendon after initial redressement and casting. The normalized position is maintained by means of an removable plastic cast and later an instep raiser. Instructions for the maintenance are given. PMID- 7985404 TI - [Histological findings of the femoral quadriceps muscle in varus and valgus gonarthrosis]. AB - A pronounced valgization or varization of the lower extremity leads to changes in skeletal muscle which are histologically and morphometrically demonstrable in biopsies of Mm. vastus lateralis et medialis of patients with chronically anomalous stressing of the knee joint. During chronic over-stressing, increased thickness in type I and type II muscle fibers can be observed in both Mm. vastus medialis and lateralis, whereas type II fibers demonstrate a greater variability and there is a greater occurrence in type I fibers. Our investigations show that a chronic anomalous stressing influences both the size and energy metabolism of a skeletal muscle cell in a manner which can be interpreted as a functional adaptation. PMID- 7985405 TI - [Clinical aspects and therapy of carpal tunnel syndrome]. AB - In a retrospective study the clinical symptomatology and the clinical results of carpal tunnel syndrome is evaluated by means of 1000 patients. The results of 1047 operated hands assessed by the patients were rated as very good 72%, good 21.2% and satisfactory 5.6%. PMID- 7985406 TI - [Diagnosis and therapy of tendovaginitis of the extensor carpi ulnaris (stenosis of the 6th extensor compartment)]. AB - Stenosing tenosynovitis over the dorsum of the wrist in the sixth compartment is seldom mentioned in literature. We have collected 28 cases in a four-year period which demonstrate that the incidence is quite high. This condition should be considered in the differential diagnosis of pain over the dorso-ulnar aspect of the wrist. On examination firm, fusiform swelling in the sixth compartment was present. Pain was elicited by active ulnar deviation against resistance. All 28 patients had local infiltration with cortisone, but only 8 patients obtained complete relief. 18 of 20 patients had complete relief of their symptoms after surgical release of the sixth compartment. We conclude that stenosing tendovaginitis of extensor carpi ulnaris is a relatively common condition. Awareness of the syndrome allows accurate diagnosis and treatment. PMID- 7985407 TI - [Ulnar groove syndrome following elbow injuries]. AB - For a large scaled test 52 patients with anterior transposition of the ulnar nerve and 62 patients with elbow injuries were examined by questionnaire, physical examination and electroneurography. In conformity with existing literature 24 patients out of 52 suffering from cubital tunnel syndrome had an elbow trauma previously. To our great surprise in seven patients out of 46 with elbow injuries a cubital tunnel syndrome could be found for the first time. The cubital tunnel syndrome appears to be a frequent complication of elbow injuries. Besides the well known fractures of the medial epicondyle and pericondylar fractures leading to cubital tunnel syndrome, in our study fractures of the head of the radius and processus coronoideus were found quite often. Patients having typical anamnesis and complaints should be checked by electroneurography in order to permit a quick operation and to prevent incurable damages of the nerve. The diagnosis leading to operation of the elbow should however be made with greatest care. In case the operation is unavoidable, the ulnar nerve should be thoroughly checked and anterior transposition should be carried out. PMID- 7985408 TI - Genetic heterogeneity of the attachment glycoprotein G among group A respiratory syncytial viruses. AB - Fifteen independent group A respiratory syncytial virus (RSV) isolates were compared by sequencing a 300-nucleotide interval encoding a variable region of the attachment glycoprotein G. The viruses compared included the reference strains Long (USA 1956), A2 (Australia 1961), and 669 (Sweden 1959), along with 13 clinical isolates obtained at different times and locations throughout the United States. Representatives of all six antigenic subgroups, recognized by reactivity patterns with monoclonal antibodies, were compared. The maximum sequence heterogeneity within the G glycoprotein region compared was 15.7% of nucleotide sequences and 26% of amino acid sequences, more than twice the difference observed between Long and A2. Half of the nucleotide changes encoded amino acid substitutions, possibly indicating that the protein interval compared was subject to immune selection. Because the ratio of nucleotide to amino acid substitutions was nearly constant for all degrees of genetic divergence, the potential range of sequence divergence among group A RSV has probably not yet been attained. There was little correlation between the patterns of reactivity against a panel of monoclonal antibodies and sequence relationships among the 15 isolates. The sequence information showed multiple genotypes circulating simultaneously in the same community and very similar genotypes circulating in widely separated communities and during different years. Genetic analyses of RSV strains can provide important information about the relationships between RSV infections. PMID- 7985409 TI - Nucleotide sequence analysis of the structural gene coding region of the pestivirus border disease virus. AB - Border disease virus (BDV) of sheep, an important ovine pathogen, is serologically related to the two other well characterized members of the Pestivirus genus of the Flaviviridae family, namely bovine viral diarrhea virus (BVDV) and hog cholera virus (HoCV). To determine its genetic relationship to BVDV and HoCV, the genome of BDV strain, BD-78 encompassing the 5' untranslated region (UTR) and structural gene coding region was molecularly cloned and the nucleotide sequence determined. The sequenced region of 3,567 nucleotides contained one open reading frame encoding 1063 amino acids. The nucleotide and amino acid sequences of BD-78 were compared with those of two BVDV strains NADL and SD-1, and the Alfort and Brescia strains of HoCV. The overall nucleotide sequence homologies of the region sequenced of BD-78 are 68.3% with BVDV-NADL, 67.8% with BVDV-SD-1, 69.0% with HoCV-Brescia, and 65.8% with HoCV-Alfort. The overall amino acid sequence homologies of BD-78 are 76.1% with NADL, 76.5% with SD-1, 74.2% with Brescia, and 72.9% with Alfort. The most conserved nucleotide and amino acid sequences between BD-78 and the other pestivirueses are in the 5' UTR and the capsid protein coding region (p14), where as the most divergent sequences are in the E2 coding region. These findings suggest that BDV is a unique virus in the Pestivirus genus. PMID- 7985410 TI - Impaired Ca2+ response to glucose in mouse beta-cells infected with coxsackie B or Echo virus. AB - Five strains of Coxsackie B4 virus and one of Echo 11 virus were tested with regard to their ability to replicate in pancreatic mouse beta-cells and interfere with the alterations of the cytoplasmic Ca2+ concentration ([Ca2+]i) induced by glucose. All strains except one both multiplied and caused cytopathic effect. In a control group 68% of the beta-cells responded to 11 mM glucose with large amplitude oscillations of [Ca2+]i. After inoculation with the infectious strains these oscillations appeared in only 5% of the beta-cells, whereas the non infectious strain did not modify the glucose effect on [Ca2+]i. Despite the virus interference with the glucose response, [Ca2+]i was increased after depolarization with excessive extracellular K+ and the oscillations were induced in most beta-cells when glucose was combined with the insulin-releasing sulfonylurea tolbutamide. PMID- 7985411 TI - Attenuated temperature-sensitive respiratory syncytial virus mutants generated by cold adaptation. AB - Two strains of respiratory syncytial virus (RSV), RSV 2B and RSV 3A (representing subgroup B and A virus respectively) were cold-adapted by passaging in Vero cells for up to 42 weeks at successively lower temperatures down to 20 degrees C. Successful cold adaptation of the virus population was dependent on the amount of time the cultures were maintained at the various low temperatures, as well as on the strain of virus used. Temperature-sensitive (TS) mutants appeared in the cold passaged virus populations; however, the majority of the virus variants remained predominantly non-TS. Four RSV 2B and three RSV 3A TS mutants were selected for further characterization. These seven TS mutants retained their fusion phenotype and two major neutralizing antibody epitopes, and displayed varying levels of temperature sensitivity. Six of the seven mutants had a cold-adapted (CA) phenotype. All of the RSV 2B mutants were highly attenuated in cotton rats and two of the mutants elicited relatively high levels of neutralizing antibody and were able to protect rats against virus challenge. The RSV 3A TS mutants grew well in the nose but poorly in the cotton rat lungs, as did the parental 3A virus. All 3A mutants elicited high titers of neutralizing antibody and provided complete protection against virus challenge. These mutants showed varying levels of temperature sensitivity in vitro and attenuation in vivo and represent potential vaccine candidates. PMID- 7985412 TI - Virus-like particles in MDCK cells persistently infected with Borna disease virus. AB - A line of Madin Darby canine kidney (MDCK) cells persistently infected with Borna disease virus was examined by electron microscopy. Thin sections revealed the presence of intracytoplasmic virus-like particles ranging from 50-100 nm in diameter. Nuclei of the infected cells exhibited accumulation of electron-dense granular structures 15-18 nm in diameter. The intracytoplasmic particles were roughly spherical with a limiting membrane, suggesting the presence of a lipid containing envelope. The internal structure consisted of strand-like material which in some cases was condensed underneath the envelope. The possible relationship of these particles to Borna disease virions is discussed. PMID- 7985413 TI - Nucleotide sequence and infectious in vitro transcripts of RNA 3 of tomato aspermy virus pepper isolate. AB - The nucleotide sequence of a cDNA clone corresponding to the entire RNA 3 of a pepper isolate of tomato aspermy cucumovirus (P-TAV) was determined. The 2222 nucleotides (nt) long RNA 3 is dicistronic and codes a 3a (280 amino acids) and a coat protein (cp, 218 amino acids). The nucleotide sequence of P-TAV RNA 3 shows a high sequence identity (99%) with that of C-TAV RNA 3 and the amino acid sequences of the 3a and the coat proteins between these two TAV strains are also very similar. The transcription start site of the subgenomic RNA 4 was mapped to the G at the position of 1148 of RNA 3. A full-length cDNA copy of P-TAV RNA-3 was cloned downstream of the phage T7 promoter. Transcripts synthesized in vitro had no extra nucleotides at the 5' end, but there were nine non-viral nucleotides at the 3' terminus. The transcripts of TAV RNA 3 were infectious when coinoculated into test plants in the presence of purified RNA 1 and 2 of P-TAV or Trk7-CMV respectively. Northern blot analysis of RNA extracted from inoculated plants showed the expected genomic and subgenomic RNAs. PMID- 7985414 TI - Review: cell wall assembly in yeast. PMID- 7985415 TI - Genetic interrelationship among species of the genus Zygosaccharomyces as revealed by small-subunit rRNA gene sequences. AB - The phylogenetic interrelationship of species of the genus Zygosaccharomyces was examined by 18S rRNA gene sequencing. Comparative analysis of the sequence data revealed the genus to consist of a number of distinct subdivisions. The most prevalent species associated with food spoilage, Z. bailii, Z. bisporus and Z. rouxii, along with Z. mellis were found to form one subdivision. Zygosaccharomyces cidri and Z. fermentati formed a distinct species pair, as did Z. microellipsoides and Z. mrakii. Zygosaccharomyces florentinus formed a separate line displaying no specific relationship with any of the other Zygosaccharomyces species examined. Comparison with nine published ascosporogenous yeast 18S rRNA gene sequences showed that Z. microellipsoides and Z. mrakii were genealogically very close to Torulaspora delbrueckii (both displaying 99.8% 18S rRNA sequence similarity), raising the possibility that these two Zygosaccharomyces species should be moved to the genus Torulaspora. The topologies of trees derived from complete 18S rRNA gene sequences and from individual domains within the gene were compared and the implications of using partial sequence data for inferring phylogenetic relationships discussed. PMID- 7985416 TI - A fission yeast gene encoding a protein that preferentially associates with curved DNA. AB - We searched for fission yeast (Schizosaccharomyces pombe) proteins that preferentially bind to a synthetic curved DNA sequence, by means of a DNA-binding gel shift assay in the presence of an excess amount of a non-curved DNA sequence as a competitor. We identified such a protein in S. pombe. The protein, thus purified, has an apparent molecular weight of 42,000, as estimated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. It was suggested that this protein (42 K-protein) recognizes and binds to a curved DNA structure in a given nucleotide sequence, although it also binds to a non-curved DNA sequence with lower affinity. As its putative coding sequence, a 1.9-kilobase genomic DNA from S. pombe was cloned and sequenced. Sequencing of a cDNA clone also revealed the existence of an open reading frame, with no intron, encoding a 381-amino-acid protein with a calculated molecular mass, 41,597. This protein appears to be located in the nucleus. The predicted protein sequence revealed that the 42 K protein exhibits no significant similarity to any other known proteins, except to a hypothetical protein of Caenorhabditis elegans. PMID- 7985417 TI - Mating in the heterothallic haploid yeast Clavispora opuntiae, with special reference to mating type imbalances in local populations. AB - Mating was studied in the haploid, heterothallic yeast Clavispora opuntiae to assess the importance of nutritional, genetic, and other factors that may favour mating and recombination. Local populations of this yeast generally exhibit dramatic inequalities in mating type distributions, suggesting that mating is rare in nature even though most isolates mate freely in the laboratory. The absence of assimilable nitrogen is prerequisite to mating competence, presumably by causing G1 arrest. Maximum mating competence is found in cells entering stationary phase in nitrogen-limited media. Unlike the vast majority of mating yeasts, C. opuntiae does not appear to produce diffusible mating factors (sex pheromones), and mating-competent cells do not undergo sexual agglutination. Pairwise cell contact appears to be the only signal that triggers the sexual process in this case. In order to determine if mating type imbalances in nature are caused by reduced fertility of 'consanguine' crosses, meiotic recombination was measured in pairs of strains that varied in their genetic distances as indicated by restriction mapping. That hypothesis was rejected, as recombination efficiency decreased with increasing genetic distance. We conclude that the rarity of mating in local populations is exacerbated by the stringent physical (pairwise cell contact) and nutritional (nitrogen depletion) conditions that will allow mating to proceed. Parallels are drawn with mating patterns observed in Clavispora lusitaniae. PMID- 7985418 TI - Formation of poliomyelitis subviral particles in the yeast Saccharomyces cerevisiae. AB - The sequence of the poliovirus genome encoding 3CD (a protease) was transferred to the yeast Saccharomyces cerevisiae on expression vectors with either a constitutive or an inducible promoter. Transformants could only be obtained with vectors carrying the inducible transcription unit. Extracts of induced cells were able to cleave cell-free synthesized P1, the precursor of the poliovirus capsid proteins, into VP0, VP3 and VP1. In yeast cells constitutively expressing P1, induction of 3CD expression resulted in only trace amounts of processed products. Processing could be improved considerably by simultaneous induction of both P1 and 3CD expression. Analysis of extracts of such induced cells revealed the presence of particles that resembled authentic subviral particles. PMID- 7985419 TI - Cloning and sequencing of Schizosaccharomyces pombe car1 gene encoding arginase. Expression of the arginine anabolic and catabolic genes in response to arginine and related metabolites. AB - We report here the cloning and sequencing of the gene encoding arginase (car1) from Schizosaccharomyces pombe. Since no arginase-less strain exists in this organism, we cloned the gene by functional complementation of a car1 mutant strain from Saccharomyces cerevisiae. The S. pombe car1 gene encodes a 323 amino acids polypeptide sharing identity with arginases from different organisms. Measurements of arg3, arg11 and car1 mRNA under different growth conditions confirm the very weak repression by arginine of the two anabolic genes and show that the induction of arginase synthesis operates at a transcriptional level. The promoter of S. pombe car1 gene does not contain the 'arginine boxes' defined as the target of the ARGR-MCM1 proteins in the promoters of the arginine co regulated genes in S. cerevisiae. The heterologous expression of S. pombe car1 gene in S. cerevisiae is independent of the ARGRII gene product (ArgRIIp/Arg81p). Determination of arginine, ornithine and citrulline intracellular concentrations shows the efficiency of the different controls operating in S. cerevisiae, and also indicates that in S. pombe enzyme compartmentation is not always sufficient to control the arginine metabolic flux. PMID- 7985420 TI - The peroxisomal targeting signal of 3-oxoacyl-CoA thiolase from Saccharomyces cerevisiae. AB - All peroxisomal 3-oxoacyl-CoA thiolases identified so far do not contain the previously identified tripeptide peroxisomal targeting signal at their carboxy termini. For the two rat thiolases it was shown that their peroxisomal targeting signals are localized within the amino-terminal region of the proteins and are cleaved upon import. This report demonstrates that the N-terminal region of the peroxisomal 3-oxoacyl-CoA thiolase from Saccharomyces cerevisiae is essential for its peroxisomal targeting, and that the N-terminal 16 amino acids of yeast thiolase are sufficient to target the otherwise cytosolic small subunit of ribulose-1,5-bisphosphate carboxylase to peroxisomes for import. PMID- 7985421 TI - Nucleotide sequence analysis of an 8887 bp region of the left arm of yeast chromosome XIV, encompassing the centromere sequence. AB - The nucleotide sequencing of 8887 bp of the left arm of chromosome XIV is described. The sequence includes the centromeric region. Both strands were sequenced with an average redundancy of 5.09 per base pair. The overall G+C content is 37.3% (39.2% for putative coding regions versus 32.5% for non-coding regions). Six open reading frames (ORFs) greater than 100 amino acids were detected, all of which are completely confined to the 8.9 kbp region. Codon frequencies of the six ORFs agree with codon usage in Saccharomyces cerevisiae and all show the characteristics of low-level expressed genes. Comparison of the translated sequences with protein sequences in data bases suggests the presence of two ORFs (N2014 and N2007) encoding ribosomal proteins, the latter of which is the previously sequenced MRP7 gene. Another ORF (N2012) could encode a membrane associated protein since it contains secretory signal sequence and two presumed transmembrane helices. This protein might be involved in mitochondrial energy transfer. ORF N2016 is immediately adjacent to the centromere, suggesting that it corresponds to the SPO1 gene, which is very tightly linked to the centromere at the left arm side of chromosome XIV (Mortimer et al., 1989). PMID- 7985422 TI - LTE1 of Saccharomyces cerevisiae is a 1435 codon open reading frame that has sequence similarities to guanine nucleotide releasing factors. AB - The DNA sequence of the LTE1 gene on the left arm of chromosome I of Saccharomyces cerevisiae has been determined. The LTE1 open reading frame comprises 4305 bp that can be translated into 1435 amino acid residues. The position of this open reading frame corresponds well to that of a 4.7 kb transcript that has been mapped to this position. The derived amino acid sequence has significant similarities to the amino acid sequence of the guanine nucleotide releasing factor isolated from a rat brain library. The carboxy-terminus of the LTE1 protein also shows similarities to other guanine nucleotide exchange factors of the S. cerevisiae CDC25 family. PMID- 7985423 TI - Sequence analysis of a 31 kb DNA fragment from the right arm of Saccharomyces cerevisiae chromosome II. AB - The nucleotide sequence of a 31,352 bp fragment from chromosome II of Saccharomyces cerevisiae has been determined and analysed. The fragment originates from the right arm of chromosome II, located between the GAL7,10,1 and the PHO3,5 loci, at a distance of about 130 kb from the centromere. The sequence contains a tRNA tandem repeat and 17 open reading frames (ORFs) larger than 100 amino acids. One of them extends into adjacent DNA and is incomplete. The two tRNA genes, coding for a tRNA(asp) and a tRNA(arg), and three of the ORFs, had been sequenced previously, i.e. HSP26, SEC18, and UBC4. Four other ORFs showed similarity with yeast genes; amino acid transporter genes, the RAD54, SNF2 and STH1 family, the SPS2 gene and the bromodomain of SPT7, respectively. Two showed homology with sequences from other organisms, i.e. with a Plasmodium falciparum gene encoding a surface antigen and with a gene from Saimirine herpes virus respectively. Three ORFs, YBR0726, YBR0735 and YBR0740 are completely contained in YBR0727, YBR0734 and YBR0739 respectively, and thus probably do not represent real genes. Two ORFs, YBR0727 and YBR0745 most likely contain an intron. PMID- 7985424 TI - Sequence and function analysis of a 9.46 kb fragment of Saccharomyces cerevisiae chromosome X. AB - In the framework of the European yeast genome sequencing project, we have determined the nucleotide sequence of the cosmid clone 233 provided by F. Galibert (Rennes Cedex, France). We present here 9464 base pairs of this cosmid located on the left arm of Saccharomyces cerevisiae chromosome X. This sequence contains two new open reading frames and includes the published sequences of the RADH gene (also identified as SRS2/HPR5) and the 3'-end of the gene BCK1/SLK1/SSP31. Deletion mutants of the two unknown genes J0909 and J0911 are viable. PMID- 7985426 TI - Current awareness on yeast. PMID- 7985425 TI - Obituary. In memory of Seymour Fogel. PMID- 7985427 TI - [10th Annual meeting of the German Association for Vascular Surgery. Dusseldorf, 11-14 May 1994. Proceedings]. PMID- 7985428 TI - Lymphocyte subpopulations in jejunal and ileal Peyer's patches of calves with experimental Salmonella dublin infection. AB - Changes of lymphocyte subpopulations in jejunal and ileal Peyer's patches (JPP and IPP) of six calves inoculated with Salmonella dublin were investigated at 9 hours, 1, 2, 3 and 7 days post inoculation (p.i.) using immunohistochemistry. Reactive areas and area percentages of B-lymphocytes, as well as CD4+, CD8+ and gamma delta T-lymphocytes within the different compartments of PP were estimated using computer-assisted morphometric analysis. A significant, linear decline of the areas of lymphoid follicles and domes in JPP and IPP due to depletion of B lymphocytes was found. The rate of decline was similar in JPP and IPP, but more severe in lymphoid follicles than in domes. Intraepithelial cells in follicle associated epithelium changed from predominantly B-lymphocytes in controls to CD8+ T-lymphocytes in inoculated calves and clusters of B-lymphocytes were observed above domes at days 1 and 2 p.i. Areas of CD4+ and CD8+ T-lymphocytes within lymphoid follicles and domes were increased at 3 and 7 days. p.i. resulting in decreased compartmentalization of the normally segregated T- and B lymphocyte populations. The increase of CD4+ and CD8+ T-lymphocytes was, however, significant in lymphoid follicles in the JPP only. No significant changes in the amount and distribution of gamma delta T-lymphocytes were observed. PMID- 7985429 TI - [Scanning electron microscopic studies of the urinary bladder of sows with special reference to a Eubacterium suis infection]. AB - Scanning electron microscopy was performed on bladder biopsies from 20 sows with cystitis. Results were compared with those of healthy control animals. Biopsy specimens were taken from nine sows infected only with commensal bacteria (E. coli, streptococci, staphylococci) and from 11 sows, where Eubacterium suis (E. suis) was involved in urinary tract infection and had caused a haemorrhagic cystitis. Increased losses of normal superficial cells covered with microplicae could be seen depending on the degree of cystitis. Desquamation of the surface layer exposed smaller cells patterned with short microvilli. These cells were presumed to be immature intermediate cells and goblet cells. Goblet cells were found only in infected organs. The varying surface structure of epithelial cells in relation to receptor quality is important for the bacterial adherence to bladder mucosa. All examined bladders infected with E. suis showed a total loss of superficial cells. Luminal cells covered with multiple short microvilli were accompanied by cells with long pleomorphic processes. Accumulating cell necrosis was indicated by a smooth surface structure. Funnel-shaped orifices between the epithelial cells were identified as excretory ducts of mucus-filled cysts, which are formed by the confluence of degenerating goblet cells. E. suis infection of the porcine bladder causes more severe alterations than infections due to other bacteria. However, debilitation of the urothelium due to previous infection is necessary to support infection of the bladder with E. suis. PMID- 7985430 TI - Effect of adjuvant formulations on the induction of virus-neutralizing and virus binding antibodies by chemosynthetic peptides of VP1 of foot-and-mouth-disease virus. AB - Synthetic peptides corresponding to the 141-160 amino acid sequence of the protein VP1 of virus type O1 Kaufbeuren (O1K) and A5 Riems (A5R) were conjugated to thyroglobulin and mixed with complete Freund's adjuvant (CFA) or incomplete Freund's adjuvant (IFA) together with Quil A. Although the peptide of A5R, together with IFA and Quil A, or with CFA, elicited a high antibody response to the virus in the ELISA, formula containing both IFA and Quil A induced only high titres of virus-neutralizing antibodies in rabbits. These adjuvant formulas did not display significant differences with regard to side effects. PMID- 7985431 TI - Isolation of mycoplasmas from clinically healthy adult breeding geese in Germany. AB - Cloacal swabs from adult breeding geese of both sexes from six separate farms were culturally examined for mycoplasmas. Geese from these flocks did not show any clinical signs of illness, increased mortality or drop in egg production during the reproductive season. The results revealed the presence of mycoplasmas in all the flocks tested. Mycoplasma (M.) cloacale was found in 6 flocks, M. anseris in 4 flocks, Mycoplasma species 1220 in 3 flocks and non-identifiable Mycoplasmas in 2 flocks. More than one Mycoplasma species was simultaneously isolated from 14 out of 37 geese. PMID- 7985432 TI - Detection of canine parvovirus DNA in paraffin-embedded tissues by polymerase chain reaction. AB - Canine Parvovirus (CPV) is seemingly a 'new' virus which suddenly appeared during the mid-1970's in an epizootic of disease in dogs. The virus is very similar to the feline panleukopenia virus (FPV), and recent studies have underlined the possible emergence of CPV as a variant of a virus from some other carnivore- possibly from FPV (Parrish, 1990). Several conserved amino-acid changes between CPV and FPV isolates have been defined by cloning and sequencing the capsid protein gene. An alternative to cloning and sequencing the entire capsid-protein gene would be to use PCR amplification of short regions of the gene containing the appropriate variable amino-acid codons. In addition, use of PCR would also facilitate the study of virus samples which cannot be recovered as infectious agents, e.g. after having undergone formalaldehyde fixation and paraffin embedding procedures. This study reports on the amplification of CPV DNA from 15 year-old tissue sections which have been prepared by formaldehyde or paraformaldehyde-lysine-periodate-glutaraldehyde fixation, using PCR with various primer pairs within the capsid-protein gene of CPV. PMID- 7985433 TI - Effects of concurrent oral administration of lead, selenium or monensin on hepatic porphyrin levels in broiler chickens during sub-acute toxicosis. AB - Liver-porphyrin levels were found to have increased during sub-acute lead toxicosis. The presence of selenium or monensin in the diet of lead-intoxicated birds resulted in a further increase of liver-porphyrin levels. The results of this study indicate the presence of an interaction between lead and selenium or monensin in producing an increase in porphyrins in the liver tissue of broiler chickens. PMID- 7985434 TI - A 'novel' infectious bronchitis strain infecting broiler chickens in Italy. AB - An outbreak of severe respiratory disease in flocks of broiler chickens was associated with the isolation of a 'novel' strain of infectious bronchitis virus (IBV). The isolate, designated 624/I, was isolated from 9 of the 11 flocks sampled. The results of cross neutralisation and haemagglutination-inhibition tests showed isolate 624/I to be antigenically distinct from several European and American strains. In a serological survey carried out on affected flocks, specific antibodies to IBV strain 624/I and turkey rhinotracheitis (TRT) virus were detected. PMID- 7985435 TI - Prepartum antibiotic therapy with a cephapirin dry-cow product against naturally occurring intramammary infections in heifers. AB - Intramammary infusion of a dry-cow antibiotic preparation containing 300 mg of cephapirin benzathine into 18 Jersey heifers, 10-12 weeks prepartum, resulted in cure rates of existing intramammary infection (IMI) of 96% (24/25), 100% (4/4), and 90% (28/31) for Staphylococcus aureus, Streptococcus species, and Staphylococcus species, respectively. Cure rates of IMI that had been treated with a lactating-cow therapy containing 200 mg cephapirin benzathine at parturition were 62.5% (15/24), 100% (22/22), and 100% (3/3) for Staphylococcus aureus, Streptococcus species, and Staphylococcus species, respectively. Initial somatic cell counts (SCC) of secretions from infected quarters were greater than from uninfected quarters. At 2 months postpartum, the SCC of milk from treated and cured quarters were reduced in comparison with quarters that remained infected. Cephapirin benzathine was present at detectable concentrations in 94, 80, 68, and 61% of treated quarters at 1, 2, 3, and 4 weeks after infusion of the cephapirin dry-cow product, respectively. At parturition, 24% of treated quarters were positive for antibiotic, however, no quarters remained positive for antibiotic at 5 days postpartum. An additional 40 heifers from a commercial herd were sampled and infused in all quarters with the cephapirin dry-cow product at 16-20 weeks prepartum. Cure rates for the commercial herd were 94% (29/31), 94% (16/17), 100% (44/44), and 100% (3/3), respectively, for quarters infected by S. aureus, Streptococcus species, Staphylococcus species, and coliforms. PMID- 7985436 TI - [Immune status dynamics in different lateralizations of focal traumatic brain lesions]. AB - The changes occurring in the immunity of 118 patients with focal brain injuries verified at surgery and during computed tomography were studied in relation to hemispheric lateralization. Patients with left-sided brain injuries showed more severe abnormalities of immunity and had a considerable lot of pyoinflammatory complications, including extracerebral ones. In patients with right-sided brain injuries, compensation of the changed immune responses occurred more rapidly, but intracranial pyoinflammatory complications took place more frequently. The magnitude and changes in immunity were found to depend upon the hemispheric lateralization of focal brain injuries, which characterizes that the brain regions play unequal role in the formation of an immune response. Differences become significant at week 3 at the peak of secondary immunodeficiency. PMID- 7985437 TI - [External respiratory functions and pulmonary hemodynamics in patients with neurotrauma]. AB - To study abnormal external respiration function and pulmonary circulation in patients with severe brain injury, a total of 120 victims were examined. The static and dynamic parameters of external respiration function and pulmonary hemodynamics were determined every day within the first week and on days 10, 14, 21, and 28 of postinjury. The findings indicated that the causes of impaired external respiration function and circulation in brain injuries were decreases in lung volumes and capacities, disturbances in bronchial patency and alveolar ventilation uniformity followed by the development of lung and lung shunt atelectasis, changes in pulmonary circulation and elevations in pulmonary diastolic pressure, which depend upon the severity of an injury. At the same time it was found that patients with severe brain contusion developed bronchospasm, pulmonary hypertension with lesser pulmonary circulation twice more frequently than did those with moderate injuries. PMID- 7985438 TI - [The surgical treatment of meningiomas of the superior sagittal sinus (the surgical approach and technic)]. AB - The authors analyze the results of surgical management of 242 patients with upper sagittal sinus meningiomas who have been treated in the past 20 years. All the patients were divided into 3 groups in accordance with the surgical policy and techniques of interventions and anesthesiological support. The type of sinus wall tumor lesion and its associated cerebral blood outflow disorders detected by electrophysiological studies in pre- and intraoperative periods determined surgical policy which along with microsurgical technique of recovery of the intact sinus and superficial veins of the brain enhanced the efficiency of operations up to 92.2% and reduced fatal outcomes to zero. PMID- 7985439 TI - [The immunobiochemical composition of the blood and cerebrospinal fluid in the recurrence of meningeal tumors]. AB - The analysis of immunological responsiveness and factors of nonspecific resistance in patients with relapsing meningiomas shows that there are prevalent autoimmune responses in the preoperative period and their gradual, but not final overcoming by the body after elimination of neoplastic relapse. At the same time the pathogenesis is closely associated with the formation of the autoimmune status in the peripheral system to a lesser extent and in the local immune one, to a greater extent after removal of primary meningioma in a patient. PMID- 7985440 TI - [The anatomical x-ray validation of microsurgical treatment methods in intervertebral hernias of the lumbosacral spine]. AB - The microsurgical anatomy of the lateral region of the lumbosacral region of the vertebral canal was studied in 15 human cadavers. The vertebral canal and intervertebral foramina were X-ray studied in 10 healthy subjects and in 50 patients with lumbar osteochondrosis. The morphological and X-ray findings were used in the development of microsurgical methods for removing lumbar discal hernias, which were employed in 40 patients with this abnormality. The control group included 50 patients with discal hernias who had been operated on by the conventional methods. The advantages of microsurgical methods have been indicated. PMID- 7985441 TI - [The transplantation of embryonic nerve tissue in syringomyelia: initial clinical experience]. AB - The paper gives clinical findings of 5 cases of syringomyelia surgical treatment using neurotransplantation of embryonal spinal marrow nerve tissue into the intramedullary cavity. It also discusses problems of sampling, culture and transplantation of embryonal spinal marrow nerve tissues, as well as the results and prospects of this method application. PMID- 7985442 TI - [Ethical and judicial problems and the late results in patients with psychopathological disorders]. PMID- 7985443 TI - [Surgical results in intracerebral hematomas using stereotaxic puncture aspiration under guided ultrasonic brain scanning]. AB - The paper outlines experience gained in stereotaxic aspiration of intracerebral hematomas in 27 patients within 1 to 20 days after hemorrhage. Hematomas of hypertensive and traumatic origin were present in 24 and 3 patients, respectively. Puncture and decision to remove hematomas were made according to operative ultrasonic scanning evidence. Aspiration was performed by an electric mechanical aspirator. Seven patients with hypertensive hematomas died after surgery. The advantage of the procedure is that the completeness of hematoma removal can be monitored just during an operation. PMID- 7985444 TI - [The surgical treatment of an aneurysm of the unpaired anterior cerebral artery]. PMID- 7985445 TI - [Mutism following neurosurgical operations in children]. PMID- 7985446 TI - [Surgery of the femoral nerve with an injury in the retroperitoneal space]. PMID- 7985448 TI - [A hydrodynamic model of shunting systems in the treatment of hydrocephalus]. PMID- 7985447 TI - [The microsurgical revascularization of foci of cerebral ischemia with an autograft of the greater omentum]. PMID- 7985449 TI - [Hydrocephalus and its significance in the early surgical treatment of cerebral aneurysms]. AB - The clinical course of acute arterial aneurysm rupture and computed tomographic findings of the brain were analysed in 100 patients. Hydrocephalus was detected in 27% of cases. There was a relationship between the development of hydrocephalus and the nature of intracranial hemorrhage, the site of aneurysm, as well as the specific features of neurological symptomatology in hydrocephalus. Analyzing the results of surgical treatment of aneurysms in 85 patients indicated that there was an increase in the number of unfavourable functional outcomes and a decrease in good ones after early operations made in the presence of hydrocephalus. PMID- 7985450 TI - [The differential treatment of focal lesions of the frontal lobes]. AB - The differential policy of surgical and drug therapies was evidenced by comprehensive clinical, computed and magnetic resonance tomographic studies and follow-up of 113 patients with focal frontal lobar lesions. Five-year follow-up findings show that mild and moderate posttraumatic focal changes and mild posttraumatic diffuse changes detected by CT and MRT data favour a better clinical recovery and satisfactory social and working rehabilitation in most victims with crushing foci and intracerebral hematomas of the frontal lobes. PMID- 7985451 TI - Fertilization of oocytes by testicular spermatozoa and pregnancy in the human. PMID- 7985452 TI - LUF-syndrome biological diagnosis by basal body temperature (BBT) graph. AB - 73 consecutive patients were monitored and submitted to ambulatorial screening for primary infertility. In all of them was also performed a study of the BBT behaviour and the results reported on a graph. All these with LUF syndrome had substantial deviation of the BBT graphs. This observation can make us obtain a new parameter and a first diagnostic approach in the study of the ovulatory infertility. PMID- 7985453 TI - Reproductive performance in women with bicornuate uterus. AB - The medical records of 21 patients with bicornuate uterus were analyzed. Thirteen patients did not undergo corrective surgery, whereas eight underwent metroplasty. The pregnancies in patients who did not undergo surgery, and the outcome evaluated. The outcome of pregnancies after corrective surgery was also analyzed. The cumulative pregnancy rates at 12 and 24 months were 67% and 95% in patients without surgical correction and 63% and 88% in patients after surgical correction. The probability of giving birth to a live-born infant with no corrective surgery was 30%, 58% and 79% for the first, second and third pregnancy respectively; the probability of giving birth to a live-born infant after corrective surgery was 71% for the first and 86% for the second pregnancy. Fertility is not impaired in patients with bicornuate uterus, but gestational capacity is. A prognostic estimate of the likelihood of giving birth to a live born infant can be formulated according to the number of pregnancies and/or surgical correction. PMID- 7985455 TI - Intrauterine insemination as a successful method in the treatment of infertility caused by oligospermia. AB - Intrauterine insemination combined with controlled ovarian hyperstimulation was used in treating couples with infertility problem caused by oligospermia. We reported 85 cases, with sperm number less than 20.0 x 10(6) per insemination sample. We obtained successful insemination with 0.7 x 10(6) motile sperm cells per insemination sample. We were particularly successful in treating severe oligospermia. Most of the pregnancies in our population of patients ended in delivering singletons. In conclusion, infertility caused by oligospermia may be successfully treated using IUI with controlled ovarian stimulation. Our opinion is that the accuracy of IUI timing is critical, especially when severe oligospermia is concerned. PMID- 7985454 TI - The surgical correction of varicocele: multidisciplinary study on semen evaluation and prognostic factors for fertility. AB - The seminal pattern was studied in a group of 52 patients before and six months after sclerotherapy of varicocele. In this series, we studied the differences in clinical and seminal characteristics between the group that succeeded in obtaining a pregnancy and the group that remained infertile after 1 year follow up. The difference in pregnancy rate is discussed between the operated group and a control group of pz, who refused any form of surgery, after 1 year follow-up. PMID- 7985456 TI - Hypothesis: improving the semen quality. AB - Author proposes repeated ejaculations as a method for improving the semen quality in terms of total spermatozoa count and the percentage of motile spermatozoa. This must be helpful to many oligozoospermic, oligoasthenozoospermic and asthenozoospermic patients. PMID- 7985457 TI - The hormonal control of endometrial receptivity in egg donation and IVF: from a two to a multi-player senario. PMID- 7985458 TI - Evaluating endometrial adequacy for oocyte donation. PMID- 7985459 TI - Embryo implantation rates in stimulated and hormonal replacement cycles: uterine versus tubal transfers. PMID- 7985460 TI - Ovum donation in postmenopausal women: what are the limits? PMID- 7985461 TI - Pregnancy "quality" in older women: risks and complications related to age. PMID- 7985462 TI - Adoption vs. gametes donation: analysis of a dilemma. PMID- 7985463 TI - Effects of controlled ovarian hyperstimulation on corpus luteum and endometrial function. PMID- 7985464 TI - Markers for establishing the adequacy of embryonal development in assisted conception. PMID- 7985466 TI - Assisted hatching: indications and techniques. PMID- 7985465 TI - Factors affecting human blastocyst formation in vitro and freezing at the blastocyst stage. AB - Whatever the culture medium, embryo culture generally leads to a major loss of viability in mouse, rabbits even if the morphological development of the embryo is preserved. Moreover, Embryo metabolism is commonly depressed in culture media. The protein turnover is accelerated and the quality of the metabolites transport systems is impaired. Various coculture systems have been designed to avoid this loss of viability and in some animal species, to overcome the so called "embryo developmental arrest" usually observed at the approximate time of genomic activation. Moreover, it is clear now that cocultured embryos have usually higher cells numbers than those observed for embryos cultured in classical culture media. In the human, the problems seem less complicated because embryos can be transferred into the uterus on the second day post fertilization, at a time when they would normally be in the Fallopian tube: this is not possible in animal species. Also, blastocysts can be obtained, even at low rates, in conventional culture media and there is no apparent block of development. In this paper, we will present an overview of Cocultures in different species. Then, we will focus on the Human including the blastocyst formation rate and freezing at the Blastocyst stage. At the beginning of the Story, For coculturing, 2 ideas were put forward: The use of embryonic tissue (trophoblast) to help the embryo through an autocrine effect. The use of female genital tract cells, to assist the embryo through a paracrine effect. PMID- 7985467 TI - Mechanisms involved in the decidualization of human endometrial stromal cells. AB - Nearly homogeneous preparations of stromal cells derived from human proliferative endometrium can be obtained by treating endometrial fragments with collagenase in order to disperse stromal elements, filtering the mixture a 25 microns opening sieve to separate them from gland, and incubating the dispersed cells to culture dishes. Exposure of stromal cell cultures to db-cAMP, 8-Br-cAMP or forskolin in RPMI 1640 medium containing 2% ct-FCS and 0.1 U/ml insulin induces the expression of prolactin (PRL), evident from 1) its secretion to the culture medium, measured by radioimmunoassay and by Western blot analysis, 2) the incorporation of 35S methionine in a protein precipitated with a PRL antibody and co-migrating with authentic PRL during electrophoresis, and 3) the synthesis of PRL mRNA determined by Northern blot analysis. The cAMP effect on PRL production is enhanced by progestins, which by themselves are weak PRL inducers under similar experimental conditions. As expected from previous findings in our laboratory, showing that addition of PRL to the culture medium induces decidualization of endometrial stromal cells, cAMP derivatives not only induce PRL but also provoke differentiation of the fibroblast-like stromal cells to the decidual phenotype, as evident from morphologic changes and by the expression of products characteristic of decidual cells, e.g. IGFBP-1, desmin, hsp 27 and laminin. These findings suggest a PRL-mediated, progesterone-enhanced decidualization mechanism initiated by physiologic agents increasing cAMP levels in stromal cells. PMID- 7985468 TI - Endometrial protein secretion during the peri-implantation phase and early pregnancy. PMID- 7985469 TI - Sperm physiology: new developments. PMID- 7985470 TI - Clinical evaluation of male factor: what is critical? PMID- 7985471 TI - Pharmacologic treatment of idiopathic oligoasthenoteratozoospermia. PMID- 7985472 TI - Enhancing sperm fertilizing capacity in vitro: indications and limits. PMID- 7985473 TI - Gametes micromanipulation. PMID- 7985474 TI - Epididymal aspiration of nemasperms (MESA). PMID- 7985475 TI - Selection of patients with monoclonal gammopathy of undetermined significance is mandatory for a reliable use of interleukin-6 and other nonspecific multiple myeloma serum markers. AB - Serum levels of various immunochemical markers of clinical interest, as interleukin-6 (IL-6), C-reactive protein (CRP) and beta 2-microglobulin (beta 2M), were measured in sera from 98 subjects affected with monoclonal gammopathy of undetermined significance (MGUS; 80% of which bearing cancer too) and from 39 patients with multiple myeloma (MM). In addition, the ratio between serum IgG/IgA amounts (GAR) was also calculated in monoclonal gammopathies of IgG type. Consistent with our previous investigations, we found that tumor presence significantly influenced the serum levels of the various markers (except GAR) in MGUS patients; in fact, only when comparing MGUS without tumor and MM patients, was a clear difference observed for all markers considered. The data presented discourage the use of IL-6, CRP and beta 2M as discriminant indices between MGUS and MM patients, unless a careful selection of MGUS subjects is performed. Further investigations on these potential markers are therefore needed for a more rational clinical application. PMID- 7985476 TI - Mitoxantrone and standard dose cytosine arabinoside therapy in refractory or relapsed acute leukemia. AB - Thirty adult patients with relapsing or refractory acute leukemia were treated with mitoxantrone 10 mg/m2 daily by 20-min intravenous infusion for 5 days and cytosine arabinoside (Ara-C) 200 mg/m2 daily by continuous infusion for 5 days. Complete remission was obtained in 9 of 15 patients (60%) with acute myeloblastic leukemia (AML), with a mean duration of 6 months (range 2-12 months). Among 15 patients with acute lymphoblastic leukemia (ALL), complete remission was obtained in 5 patients (33.3%), with a mean duration of 2 months. Partial remission was achieved in 2 patients with AML and 1 patient with ALL. Myelosuppression developed in all patients following chemotherapy. Nonhematologic side effects consisted of nausea, vomiting, mild alopecia, stomatitis and transient hepatic dysfunction. No cardiopulmonary toxicity or neurotoxicity was observed. Our therapeutic responses are similar to those obtained with high-dose Ara-C and mitoxantrone but with less toxicity. PMID- 7985477 TI - Acute myeloid leukemia subtypes and response to treatment among ethnic minorities in a large US urban hospital. AB - From January 1, 1987, to August 30, 1991, 86 consecutive new cases of AML diagnosed at the LAC-USC Medical Center were analyzed. A significant difference in the FAB subtypes of AML was observed among different racial groups, with AML M3 more common in Latinos (40%) and AML-M2 in Orientals (52%). Sixty-seven patients received induction chemotherapy with TAD (thioguanine-cytosine arabinoside-daunorubicin) or like regimens. Median follow-up time of all patients was 16 months. Forty-three patients (64%) achieved complete remission. The median overall survival of those who received induction was 10.5 months. The complete remission rates and overall survival were similar among patients of different ethnic backgrounds. PMID- 7985478 TI - Pure red cell anemia with erythropoietic maturation arrest and spontaneous recovery. AB - We report the case of a 21-year-old male who presented with severe anemia and hypercellular bone marrow, without known cause. The dominant feature of the bone marrow was that of a maturation arrest in the erythroid series, with absolute reticulocytopenia in the peripheral blood. Immunosuppressive therapy was withheld, but transfusions were given to maintain his hemoglobin prior to full recovery. The patient had features of both pure red cell anemia and of transient erythroblastopenia of childhood. PMID- 7985479 TI - Myelodysplastic syndrome with t(9;11)(p22;q23) after treatment for B-cell acute lymphoblastic leukemia without epipodophyllotoxins. AB - Secondary myelodysplastic syndrome (MDS) with t(9;11)(p22;q23) developed in a child after intensive treatment for B-cell acute lymphoblastic leukemia diagnosed 12 months earlier. His chemotherapy had consisted mainly of cyclophosphamide and methotrexate, but no epipodophyllotoxins. The combination of MDS, the cytogenetic anomaly involving bands at 11q23 and no previous exposure to epipodophyllotoxins represents a unique case of therapy-related leukemia. PMID- 7985480 TI - Monosomy 7 myelodysplasia in childhood. Two case reports. AB - Monosomy 7 myelodysplasia is a rare hematological entity and is associated with morphological abnormalities in bone marrow and peripheral smear, and poor prognosis in children. We describe 2 children with infantile monosomy 7 myelodysplasia which evolved to leukemia. One of them died after 1 month, and the other is still on therapy for acute myelocytic leukemia (M4) which has evolved from chronic myelomonocytic leukemia. We concluded that chromosomal analysis must be done routinely in patients with myelodysplasia, in acute myeloid leukemia and chronic myelomonocytic leukemia. PMID- 7985481 TI - Hemolytic anemia with positive direct antiglobulin test secondary to spontaneous cytomegalovirus infection in healthy adults. AB - Hemolytic anemia with positive direct antiglobulin test in association with spontaneous cytomegalovirus (CMV) infection is a very rare event in healthy adults. We report here 2 patients who have recently suffered from this complication and review similar cases previously reported in the literature. Because CMV serology is not routinely obtained as a part of hemolysis work-up, the true incidence of this complication may be underestimated. We believe that CMV infection should be considered in the differential diagnosis of hemolytic anemia in adults. PMID- 7985482 TI - Successful treatment of refractory pure red cell aplasia by buserelin acetate. AB - A 39-year-old female with autoimmune hemolytic anemia suffered from pure red cell aplasia. She received immunosuppressive agents including prednisolone, azathioprine, cyclophosphamide and methotrexate, resulting in a little improvement of the anemia for only short term. Consequently, she required multiple red cell transfusions for 3 years. She received buserelin acetate, a gonadotropin-releasing hormone analogue. Thereafter, the anemia dramatically improved. The direct effect of buserelin on hemopoietic progenitors was not detected in the in vitro culture study. It is most likely that buserelin enhanced erythropoiesis through the alteration of hormonal milieu. The usefulness of buserelin in the treatment of refractory pure red cell aplasia is discussed. PMID- 7985483 TI - Capnocytophaga bacteremia in neutropenic patients: report of two cases. PMID- 7985484 TI - Both parents as donors for bone marrow transplantation: failure to induce tolerance and improve outcome in rabbits. PMID- 7985485 TI - Surface membrane immunoglobulin expression in chronic lymphocytic leukemia. PMID- 7985486 TI - Resolution of thrombocytopenia in a patient with lupus anticoagulant who received warfarin therapy. PMID- 7985487 TI - Marked but transitory elevation of hepatic transaminases after subcutaneous calcium heparin administration. PMID- 7985488 TI - Idiopathic thrombocytopenic purpura (ITP) PMID- 7985489 TI - Ovarian relapse and cutaneous involvement in a case of acute lymphoblastic leukaemia. PMID- 7985490 TI - New cell line from hairy-cell leukaemia producing interleukin-6 after Epstein Barr virus immortalization. AB - A hairy-cell leukaemia (HCL) cell line, HCL-O, was established from the peripheral blood of a 62-year-old Japanese patient with a unique variant of HCL strongly expressing CD21, the receptor for the Epstein-Barr virus (EBV). The HCL O cells expressed antigens similar and dissimilar to those expressed with the original hairy cells. The HCL-O cells were more mature than the original cells in their degree of B-cell differentiation, as indicated by a decrease of CD19 and surface immunoglobulin (sIg) expression together with the appearance of CD38 and cytoplasmic Ig (cIg). In addition, the cells expressed CD11c recognized by Leu M5, a monoclonal antibody usually positive for HCL. Their karyotype and Ig gene rearrangement pattern were identical to those of the original cells. The EBV genome was detected in the HCL-O cells but not in the original cells. The HCL-O cells spontaneously produced a large quantity of interleukin-6 (IL-6) in the conditioned medium, whereas IL-6 serum level was not so high. These findings indicate that the HCL-O cell line is derived from the leukaemic hairy cells and possibly, in vitro EBV infection took place easily in the original hairy cells through their CD21, resulting in subsequent immortalization. IL-6 production by HCL-O cells may be induced or enhanced by EBV, and the secreted IL-6 might play a role in their own growth or differentiation. PMID- 7985491 TI - Corticobasal degeneration: a disease with widespread appearance of abnormal tau and neurofibrillary tangles, and its relation to progressive supranuclear palsy. AB - The neuropathological findings, including immunohistochemistry and electron microscopy, of two patients with clinical findings consistent with corticobasal degeneration (CBD) are reported. Both patients showed degeneration of the precentral cortex, the substantia nigra, the pallidum, and the thalamus. Many ballooned neurons were seen in the cerebral cortex, and argentophilic, skein-like inclusions suggesting neurofibrillary tangles (NFTs) were found in the brain stem and precentral cortex in patient 1. In contrast, patient 2 clearly showed NFTs in the brain stem and dentate nucleus which were indistinguishable from those seen in progressive supranuclear palsy (PSP), while only a few ballooned neurons were found in the cerebral cortex. Gallyas silver stain showed many argentophilic inclusions suggesting NFTs in the brain stem, subcortical nuclei, and cerebral cortex in both patients. Immunohistochemistry for tau showed tau-positive neurons in the cerebral cortex, brain stem, subcortical nuclei and spinal cord, and tau positive glial cells were seen in the cerebral cortex, white matter and subcortical nuclei, and thread-like structures were seen in the cerebral cortex and white matter. Electron microscopy of the brain stem showed NFTs consisting of paired helical filaments in patient 1, and paired helical filaments and straight tubules in patient 2. Immunoelectron microscopy revealed parallel tau-positive filaments in the cerebral cortex in patient 1. From the two patients, the wide spread appearance of abnormal tau and NFTs is one of the essential pathological features in CBD, and it also appears that CBD and PSP have some common underlying pathological processes. Patient 2 is closer to PSP than patient 1 and suggests CBD would link to PSP. PMID- 7985492 TI - The neostriatum and nucleus accumbens in parkinsonism-dementia complex of Guam: a pathological comparison with Alzheimer's disease and progressive supranuclear palsy. AB - The neostriatum, nucleus accumbens and basal nucleus of Meynert (bnM) in the parkinsonism-dementia complex of Guam (Guam PDC) were examined immunohistologically, ultrastructurally, quantitatively and topographically, and the results were compared with those in Alzheimer's disease (AD) and progressive supranuclear palsy (PSP). Compared to neurologically normal controls, the number of large neurons in Guam PDC was reduced by approximately 70% in the caudate nucleus and putamen and by more than 90% in the nucleus accumbens. The decreased number of large neurons in the neostriatum was significantly correlated to that in the bnM. The remaining large neurons and many of the medium-sized neurons in the neostriatum and nucleus accumbens were immunopositive for tau protein and contained varying amounts of 21- to 25-nm-wide paired helical filaments (PHFs) admixed with straight tubules. Curly fibers and circularly arranged reactive astrocytes were seen in the nucleus accumbens of many PDC patients. Collectively, these findings, which are similar in part to those of AD and differ from those of PSP, suggest that the large neurons in the neostriatum and nucleus accumbens in Guam PDC degenerate through PHF formation, and that extremely severe loss of large neurons in the nucleus accumbens may be linked to marked degeneration of the limbic and ventral tegmental areas and nucleus dorsal raphe. PMID- 7985493 TI - Neuronal and glial tau-positive inclusions in diverse neurologic diseases share common phosphorylation characteristics. AB - Tau accumulating as paired helical filaments (PHF) in Alzheimer's disease brain is considered to be abnormally phosphorylated on distinct sites. To compare the phosphorylation state of tau-positive neuronal inclusions among diverse neurologic diseases, we have probed these lesions with three well-defined PHF/tau monoclonals, C5, M4 and tau 1, that most likely recognize three proline-directed phosphorylation sites in PHF-tau. In Alzheimer's disease brain all three monoclonals intensely immunostained intracellular neurofibrillary tangles, neuropil threads, senile plaque neurites, and "pretangle neurons" in a phosphorylation-dependent manner. They also stained, in the same manner, Pick bodies in Pick's disease, and neurofibrillary tangles and neuropil threads in various tangle-forming neurologic diseases. In most of these diseases (including Pick's disease, progressive supranuclear palsy, subacute sclerosing panencephalitis, and Alzheimer's disease) astrocytes and oligodendrocytes were found to contain tau-positive inclusions which showed the same immunocytochemical characteristics. Thus, the widely occurring tau-positive inclusions share common phosphorylation characteristics irrespective of underlying diseases or cell types. PMID- 7985494 TI - Age-related changes of the myelinated fibers in the human corticospinal tract: a quantitative analysis. AB - A quantitative analysis was made of the myelinated fibers in the lateral corticospinal tract (LCST) at the levels of the 6th cervical, 7th thoracic and 4th lumbar spinal segments in 20 patients between 19 and 90 years old, and who died of non-neurological diseases. The diameter frequency histograms of myelinated fibers of LCST showed a bimodal pattern with a sharp peak of the small myelinated fibers and broad slope of the large myelinated fibers. The ratio of small fiber to large fiber densities was significantly higher in the 6th cervical (P < 0.05) and 4th lumbar segments (P < 0.01) than in the 7th thoracic segments. The density of small myelinated fibers was significantly lowered with advancing age (P < 0.05-0.001), while that of large myelinated fibers was not significantly decreased in the aged patients, although it showed a slight age-dependent declining tendency. Age-dependent decline of small fiber density was more prominent in the cervical and lumbar segments. Retraction of the axon-collaterals from large-diameter myelinated fibers, which are abundant in the cervical and lumbar segments, may contribute to the age-related diminution of the small myelinated fibers in the LCST. PMID- 7985495 TI - An immunohistochemical study of the neuronal expression of manganese superoxide dismutase in sporadic amyotrophic lateral sclerosis. AB - Neuronal expression of manganese superoxide dismutase (MnSOD) in sporadic amyotrophic lateral sclerosis (sALS) was investigated by an immunohistochemical method. The brains and spinal cords from 11 patients with sALS and 20 normal controls (NCs) were used, and the following four nuclei (three motor nuclei and one autonomic nucleus) were examined: the oculomotor nucleus; the hypoglossal nucleus; the cervical motor nucleus; and Onuf's nucleus. Serial sections were stained by the Kluver-Barrera (KB) method and with human-MnSOD-specific antibodies. We counted the total number of neurons visible after KB staining and the total number of positive neurons after immunostaining. The average total number of neurons after KB staining was similar in sALS patients and NCs in both the oculomotor nucleus and Onuf's nucleus, but the number in the hypoglossal and cervical motor nuclei was significantly lower in sALS. The ratio of MnSOD positive neurons to total neurons visible after KB staining, calculated as an index of the expression of MnSOD, was significantly higher in the oculomotor nucleus and Onuf's nucleus, and lower in the hypoglossal nucleus in sALS patients than in NCs. In the cervical motor nucleus, the ratio in sALS patients did not differ from that in NCs. These results suggest that production of toxic superoxide radicals might be increased in sALS, and that neurons that successfully induce the expression of sufficient MnSOD can survive the disease process, while those failing to activate adequate expression of the enzyme succumb to the toxic effects of the radicals and die. PMID- 7985496 TI - Fine structural and immunohistochemical identification of perineurial cells connecting proximal and distal stumps of transected peripheral nerves at early stages of regeneration in silicone tubes. AB - Perineurial cells are specialized connective tissue cells that form a barrier between endoneurium and epineurium in normal nerves. In the present study, the formation of the perineurium after transection of rat sciatic nerves was investigated. The cord bridging the gap between proximal and distal stumps through silicone tubes was studied 3, 7, 12, 18, and 21 days after surgery using electron microscopy and antibodies against epithelial membrane antigen (EMA), a marker for perineurial cells that has thus far not been applied to the study of differentiating cells in nerve tubulation systems. Initially, a thin cord consisting of fibrin bridged the gap between the stumps. At 7 days, longitudinal cells had migrated from both stumps toward the center of the tubes on the surface of the fibrin cord. These cells were immunoreactive with anti-EMA. At 12 days, ultrastructural features of perineurial cells (desmosomes, tight junctions, actin filaments with dense bodies, tonofilaments) were prominent in these cells. Subsequently, the gap was bridged through the perineurial tube by endothelial cells, pericytes, fibroblasts, Schwann cells, and axons. At 21 days, a single large nerve fascicle ensheathed by a mature perineurium was found between the stumps. Thus, the first cells to connect proximal and distal stumps in the investigated nerve regeneration silicon chamber system are perineurial cells. Through the tube formed by these cells, blood vessels and nerve fibers bridge the gap. Therefore, establishment of a perineurial connection between nerve stumps appears to be important in the sequence of events during nerve regeneration. PMID- 7985497 TI - Ganglioglioma: a detailed histopathological and immunohistochemical analysis of 61 cases. AB - Gangliogliomas are tumors composed of intimately admixed neuronal and glial components and account for approximately 1% of all brain tumors. Here we report the histopathological findings in 61 gangliogliomas. Epilepsy was the most common presenting symptom. Most gangliogliomas were located in the temporal lobes (74%). Thirteen percent of the gangliogliomas were associated with glioneuronal hamartias. There was considerable variation in neuronal size and density, presence of binucleated neurons, calcifications, desmoplasia, lymphocytic infiltrate, pilocytic differentiation, Rosenthal fibers, location, or histological uniformity. Fifteen percent of the gangliogliomas contained areas of purely astrocytic differentiation. All tumors were examined immunohistochemically for an aberrant p53 tumor suppressor gene product and for the presence of nuclear antigens associated with cell proliferation (Ki-67, Ki-S1, proliferating cell nuclear antigen). In 45 of 61 cases (74%) labeling indices for Ki-67 were less than 1%. Nuclear labeling for Ki-67 was observed exclusively in the astrocytic component. Gangliogliomas with very large neurons had higher Ki-67 labeling indices and occurred in younger patients than gangliogliomas with small- or intermediate-sized neurons. None of the tumors had an aberrant expression of p53. The observations suggest that gangliogliomas may arise from glioneuronal hamartias through neoplastic transformation of the astrocytic component. PMID- 7985498 TI - Unmyelinated fibers in human greater auricular and sural nerves: a comparative morphometric study. AB - Since normal structural details of human greater auricular nerve (GAN) have not as yet been studied with modern techniques, light and electron microscopic findings of seven presumably normal GANs, obtained from five patients during radical neck dissection, were compared with those of normal sural nerves (SNs). In GANs there was a tendency to higher densities per mm2 and a larger number of small-diameter fibers in myelinated fibers (MFs) and unmyelinated fibers (UFs) without obvious signs of de- or regeneration. UF histograms were unimodal in both groups, with mean UF diameters being somewhat smaller in GANS than in SNs. Schwann cell complexes containing several or even numerous UFs were more frequent in GANs than in SNs. In GANs, UF often occurred focally in great numbers within large Schwann cell complexes (polyaxonal complexes), not commonly seen in normal SNs. It is concluded that these structural peculiarities in GANs reflect natural conditions in short sensory nerves irrespective of any specific function. PMID- 7985499 TI - Demonstration of neurofibrillary tangles and neuropil thread-like structures in spinal cord white matter in parkinsonism-dementia complex on Guam and in Guamanian amyotrophic lateral sclerosis. AB - This report concerns the demonstration and distribution of neurofibrillary tangles (NFTs), immunoreactive neuropil thread-like structures and dots in the spinal cord gray and white matter of six patients with parkinsonism-dementia complex on Guam and five patients with Guamanian amyotrophic lateral sclerosis (ALS). A monoclonal antibody to Alzheimer NFTs was used. NFTs were found in the spinal cord gray matter and white matter and all patients had immunoreactive neuropil thread-like structures and dots in the gray matter as well as in the white matter. They were particularly numerous in the lateral funiculus of patients with Guamanian ALS. PMID- 7985500 TI - Familial amyotrophic lateral sclerosis with a mutation in the Cu/Zn superoxide dismutase gene. AB - Several missense mutations within exons 1, 2, 4 and 5 of the gene for Cu/Zn binding superoxide dismutase (SOD1) have been discovered to be involved in the development of chromosome 21q-linked familial amyotrophic lateral sclerosis (FALS). We describe here an autopsied patient with FALS, in whom we have recently identified a novel missense mutation in exon 1 of the SOD1 gene. The neuropathological findings were compatible with those described previously in patients with FALS with posterior column involvement. This suggests that mutations of the SOD1 gene may be responsible for this form of FALS. PMID- 7985501 TI - Myopathy with ragged red fibres following renal transplantation: possible role of cyclosporin-induced hypomagnesaemia. AB - A 65-year-old man developed a painless proximal myopathy 7 years after commencing cyclosporin therapy following a successful cadaveric renal transplant. Muscle histology showed ragged red fibres and biochemical studies suggested mitochondrial dysfunction. The possible pathogenesis of this mitochondrial myopathy, particularly its relationship to cyclosporin-induced hypomagnesaemia, is discussed. PMID- 7985502 TI - Prevalence of occlusal tooth wear and its relationship to lateral and protrusive contact schemes in a young adult Indian population. AB - The aim of the present study was to investigate the prevalence and severity of occlusal tooth wear and their interrelationships with lateral and protrusive occlusal contact schemes in a young adult Indian population. The material comprised 64 individuals (age: mean = 19 years; range, 17-24 years). Assessment of wear was performed by means of a tooth-by-tooth evaluation of casts. Lateral excursive and protrusive contact relationships were recorded at the clinical examination. There was no difference in the degree of wear between women and men. Mean occlusal wear was low for the population studied compared with similarly aged Scandinavians and Saudis. No differences in the severity of wear were found in relation to lateral excursive and protrusive contact schemes. Whereas the low wear experience in the present Indian sample may be related to dietary factors, more must be understood about the various other causes of occlusal tooth wear before its functional interdependence becomes clear. PMID- 7985503 TI - A comparative histologic study of the pulp-dentinal interface in undemineralized and demineralized tooth sections. AB - This study examines cellular differences between undemineralized and demineralized tooth sections. The material comprised unerupted and partly erupted third molars. After fixation for 24 h, 10- to 15-microns ground sections were prepared from half of the tooth, using a cutting-grinding system. The sections were compared with demineralized routine sections from the other half of the tooth. Undemineralized sections showed a better capacity for preserving the tissue integration. Especially between the odontoblast layer and the predentin a low frequency of disjunctions or tears were noted. At this level of examination fixation quality and vacuole frequency (intra-cellular spaces) did not show any differences between the two methods. PMID- 7985504 TI - Influence of arch bar splinting on periodontium and mobility of fixed teeth. AB - Altogether 17 patients treated with arch bar splints fixed onto teeth were tested at the time of splint removal and approximately 5 months later. Patients were treated with intermaxillary fixation (IMF) because of either orthognathic surgery (7 patients) or mandibular fractures (10). The CPITN index was used for estimating the periodontal status, and tooth mobility was measured with Periotest. Seven patients in the orthognathic surgery group could also be examined before splinting. Periodontal status, as shown with relative proportions of various CPITN indexes, worsened due to splinting but regained its original level at control examination a minimum of 5 months after splint removal. Since the mean Periotest values did not differ between the first and control examinations in the seven patients undergoing orthognathic surgery, the analysis of the effect of splinting on tooth mobility was performed from the values obtained immediately after splint removal and at control visit. Splinting was shown to increase Periotest values more in female patients, in younger ones, and in those who were splinted for a shorter period. Teeth with the smallest roots showed greater differences in Periotest values than those with large roots, and the greatest differences in mobility were observed in incisors. PMID- 7985505 TI - Influence of phytic acid on zinc phosphate cement. AB - The influence of phytic acid on the properties of zinc phosphate cement was studied by adding 2-13 wt% phytic acid to the liquid. Improved mechanical strength and stability were found for some cements prepared from commercial powders when liquids with increased phytic acid content were used. The results indicate that the formation of increased amounts of zinc phytate has a favorable effect on the properties of zinc phosphate cement. PMID- 7985506 TI - Temporomandibular joint osteoarthrosis. Correlation of clinical and arthroscopic findings with degree of molar support. AB - The prevalence of temporomandibular joint (TMJ) osteoarthrosis and synovitis was compared in 60 patients with painful chronic locking of the TMJ. Thirty patients had reduced molar occlusion, and as controls, 30 age-matched fully dentate patients were examined. Assessment comprised clinical examination (crepitation), tomography (sclerosis and erosions), and arthroscopy (cartilage involvement) of the TMJ. Arthroscopic signs of osteoarthrosis and synovitis were frequent in both groups. The highest frequency of osteoarthrosis was diagnosed by arthroscopy. With regard to clinical signs and symptoms, tomographic signs of osteoarthrosis, and arthroscopic diagnoses, no statistical differences were found between fully dentate subjects and those with reduced molar occlusion. The results do not support the concept that prevention of TMJ osteoarthrosis is an indication for prosthetic replacement of lost molars. PMID- 7985507 TI - Psychologic factors in the etiology of amalgam illness. AB - Eleven patients with amalgam illness aged 33-50 years were investigated by psychodynamic methods. Six of them, all women, were dental nurses and hygienists exposed to amalgam/mercury both from their own dental fillings and occupationally. Four men and one woman were exposed only to amalgam/mercury from their own fillings. Assays of mercury in urine samples and in the ambient air during work routines involving the heaviest exposure indicated that the exposure was far below the levels at which even subclinical symptoms could be indicated by psychometric tests. The psychologic investigation indicated that the symptoms of amalgam illness were psychosomatic. All patients had experienced important psychic traumata in close connection with the first appearance of symptoms. It can be concluded from the psychodynamic dialogues that they had not been able to mourn for a loss in an adequate manner and that the body had been forced to symbolize the great pain in their souls. PMID- 7985508 TI - Radiographic findings in the jaws of clinically edentulous old people living at home in Helsinki, Finland. AB - In the present survey the radiographic findings in the jaws of 124 clinically edentulous old people living at home in Helsinki, Finland, were studied, using panoramic radiography supplemented by intraoral radiographs. Only 9% of the subjects had root remains. Impacted teeth were found in 4%, radiolucent lesions in 3%, and radiopaque findings in 13%. Deviations from normal condylar structure were found in 17% and mucosal thickenings in the maxillary sinuses in 7%. The mental foramen was situated at the top of the residual ridge in 42% of the subjects. Topically situated mental foramen and condylar changes were commoner in women. The radiographic oral health status of the population studied was good. PMID- 7985509 TI - The age of restorations in situ. AB - In a cross-sectional survey the age of restorations in situ was recorded in three patient groups. Group A were randomly examined regular attenders, group B were irregular attenders randomly chosen from patient treatment records, and in group C the age of posterior gold and composite resin restorations was recorded in selected regular attenders. The study material included 8310 restorations in group A, 1281 in group B, and 500 restorations in group C. The three materials amalgam, composite, and gold accounted for more than 90% of all restorations. In group A 3.3% of the restorations were scheduled for replacement. The most prevalent reasons for replacement were secondary caries, bulk fractures of the restoration, and tooth fractures. The median age of the failed restorations was fairly similar to the median age of the acceptable restorations in situ among the regular patients (group A). The data indicate median ages of 20 years for gold restorations, 12-14 years for amalgam restorations, and 7-8 years for composite resin restorations. The restoration ages were influenced by the type and size of the restoration, the restorative material used, and possibly also the intra-oral location of the restorations. PMID- 7985511 TI - Evaluation of a training program intended to calibrate examiners of temporomandibular disorders. AB - The adequacy of a training program intended to calibrate examiners of temporomandibular disorders (TMD) was evaluated. Eight examiners blindly rated 12 subjects with various TMD signs and symptoms after participating in a 5-h intense training procedure. Some examiners had earlier experience of TMD examinations, and some were newly trained. The Craniomandibular Index was used as the assessment instrument. Agreement within the whole group of examiners was low. Training tended to increase the probability of correctly registering signs. It is concluded that the program was not sufficient to create reliability among multiple examiners. More extensive training, not only to a standard but also between the different examiners, appears necessary. Revision of the examination technique is suggested, and recommendations for strengthening the calibration procedures are made. PMID- 7985510 TI - Dental radiographic findings in the elderly in Helsinki, Finland. AB - A total of 169 dentate persons, aged 76, 81, and 86 years, living at home in Helsinki, Finland, were examined by means of panoramic radiography supplemented by intraoral radiographs. The older the age group, the fewer teeth remained. Altogether 75% of the subjects had radiographically detectable caries. A high proportion of the carious teeth (62%) was found in a relatively small number (24%) of subjects. The number of carious teeth and their percentage of the total number of teeth were greater in the older age groups. The proportion of endodontically treated teeth was 19% in the 76-year-olds and 26% in the 86-year olds. Of the subjects 41% had periapical periodontitis, which was commoner in root-filled teeth (18%) than in other teeth (4%). Caries and periapical radiolucent and radiopaque findings were commoner in men. Vertical bone pockets (3 mm or deeper) were found in 51% and furcation lesions in 28% of the subjects. Compared with earlier Finnish studies, the results indicate an improving oral health status among elderly Finns. PMID- 7985512 TI - Reliability and validity of the Swedish version of the Dental Subscale of the Children's Fear Survey Schedule, CFSS-DS. AB - A Swedish version of the Dental Subscale of Children's Fear Survey Schedule (CFSS DS) was designed to be answered by parents on behalf of their children. The instrument was administered twice to the parents of 52 children aged 4 to 14 years. The children's behaviors were rated during the dental appointment immediately after the second administration. The CFSS-DS reached high values for test-retest reliability and validity. Scores equal to or exceeding 38 were found to be related to dental fear. PMID- 7985513 TI - [Pharmacokinetics of levonorgestrel after a single dose of biodegradable microspheres containing levonorgestrel in rats]. AB - Pharmacokinetics of levonorgestrel (LNG) in the form of injectable microspheres made of biodegradable co-polymer of polylactic acid and polyglycolic acid(9: 1 PLGA) that contained 17.76% LNG, were tested in rats. Rats were given a single intramuscular injection (im) of LNG microspheres at doses of 20.4, 41.1 and 83.3 mg.kg-1. Six rats were treated with a single im of LNG microcrystals at dose of 35.0 mg.kg-1. Plasma samples obtained before injection and at various time after injection were analyzed for LNG by RIA method. Peak plasma LNG level of 67.66 nmol.L-1 was obtained 4.88 h after im of LNG microcrystals, T1/2 = 5.78 d, MRT = 10.16 d and T < 0.32 nmol.L-1 = 41.50 d. Plasma LNG levels among rats after im of three different doses of LNG microspheres showed similar biphasic changes. Cmax1 (the first phase) were 15.19, 33.61 and 38.55 nmol.L-1; Tp1 were 6, 4.67 and 4.33h; Ctrough were 1.21, 4.36 and 9.06 nmol.L-1; Ttrough were 55, 53.67 and 54.83 d; Cmax2 (the second phase) were 3.80, 9.48 and 19.68 nmol.L-1; Tp2 were 100.49, 102.21 and 89.27 d; AUC were 440.27, 1082.82 and 1931.47 nmol.d.L-1; MRT were 69.23, 65.12 and 63.25 d; T < 0.32 nmol.L-1 were 167.81, 169.73 and 167.23 d after im of LNG microspheres in doses of 20.4, 41.1 and 83.3 mg (LNG).kg-1, respectively. Cmax1, Ctrough, Cmax2 and AUC showed significantly positive correlation with LNG dose, while Tp1, Tp2, Ttrough, MRT and T < 0.32 nmol.L-1 did not.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7985515 TI - [Methodological study on the determination of oxiracetam concentration in serum and urine by HPLC]. AB - A method was developed for the determination of oxiracetam concentration in serum and urine by HPLC. Acyclovir was used as an internal standard. The analytical column was a stainless-steel column (30 mm x 4.6 mm ID) filled with 10 microns Bondapak NH2. A mixture of acetonitrile and water (80: 20) as mobile phase was used at a flow rate of 1 ml.min-1. Detection was performed at 210 nm. The retention times were 6.3 min for oxiracetam and 8.1 min for the internal standard. The lower detection limits were 1 microgram.ml-1 for serum and 20 micrograms.ml-1 for urine. The precision and accuracy within-day and day-to-day for both serum and urine samples ranged from 5.0 to 10.7%. The mean recoveries were 99.7 +/- 5.9% and 99.0 +/- 5.6% for human serum and urine, respectively. The results showed that the method is simple, rapid, sensitive, reliable and good enough to be used in studying the clinical pharmacokinetics of oxiracetam. PMID- 7985514 TI - Ethnic differences in disposition of antipyrine and acetaminophen between Tibetan and Han healthy volunteers. AB - The differences in disposition of antipyrine and acetaminophen between Tibetan and Han healthy volunteers were studied in a randomized crossover design. The half-life of antipyrine was found to be 18.8 +/- 4.89 h in 16 Han and 15.0 +/- 3.02 h in 17 Tibetan (P < 0.05) and the clearance was 1.35 +/- 0.37 L.h-1 in Han and 1.71 +/- 0.44 L.h-1 in Tibetan (P < 0.05). The half-life of acetaminophen was 3.1 +/- 0.86 h in Han and 3.2 +/- 1.12 h in Tibetan (P > 0.05). The experimental results indicate that the disposition of antipyrine between Tibetan and Han healthy volunteers significantly differed, the clearance of antipyrine in Tibetan increased by 20%, but the disposition of acetaminophen between the two ethnic groups showed no difference. PMID- 7985516 TI - [Inhibitory effect of berberine on potassium channels in guinea pig ventricular myocytes]. AB - The effects of berberine on potassium channel subtypes were investigated by using patch-clamp whole cell recording techniques. Berberine is known to be effective in lowering blood glucose and ameliorating arrhythmia. Our results indicate that, berberine can prolong action potential duration (APD), decrease IK1 and outward Itail, but showed no effect on IK. In addition, berberine was also shown to antagonize cromakalim (BRL-34915) induced inhibition of APD and the increase of KATP. These suggest that berberine can inhibit voltage- dependent and ATP sensitive potassium channels. It appears that the mechanisms of antiarrhythmic and antidiabetic action of berberine might be due to its potassium channel blocking effects. PMID- 7985517 TI - [Effect of gonadotropin-releasing peptide (GRP) on LH secretion of mouse pituitary in vitro]. AB - Synthetic GRP and its analogues, GRP-NH2, [Glu7.9.14 Lys6.10] GRP (6-14), [Phe14] GRP (5-14) and [Phe14] GRP, at the concentration of 0.05 mmol.L-1 were shown to have stimulatory effect on LH secretion in cultured mouse pituitary in vitro. The luteotropin releasing activity of GRP and its analogues was estimated to be 115.4, 114.2, 140.0, 162.0 and 179.0% of the control group, respectively. Subcutaneous administration of [Phe14] GRP on days 7-9 and 1-5 of pregnancy and [Phe14] GRP (5-14) on days 2-4 of gestation at dosage of 1 mg.d-1 (each mouse) caused fetal death in 40-60% of mice. PMID- 7985518 TI - [Quantitative structure-activity relationship of P-amino-diphenyl ether analogues to inhibit cytochrome P-450]. AB - A group of p-amino-diphenyl ether analogues were tested for their activities to prolong the pentobarbital sleeping time in mice and to inhibit the demethylation of p-nitro-anisole catalyzed by untreated mouse hepatic microsomes in vitro. The stepwise multiple regression analyses were used to obtain the quantitative structure-activity relationships between the activities of inhibiting cytochrome P-450 in vitro or in vivo for the analogues and their quantum chemical indexes. The results showed that the inhibiting activities both in vitro and in vivo were correlated with the energy level of the lowest unoccupied molecular orbital (ELUMO), the nucleophilic superdelocalizabilities of the nitrogen (SN(N)) and the oxygen (SN(O)). The inhibiting activities of the analogues to cytochrome P-450 may mainly come from their ability to form cytochrome P-450 metabolic intermediate complex. PMID- 7985519 TI - Determination of methaqualone and its metabolites in urine and blood by UV, GC/FID and GC/MS. AB - A systematic procedure for the determination of methaqualone and its metabolites in blood and urine by UV spectrophotometry, GC and GC/MS was developed. Urine and blood samples were from a suicidal patient who ingested 18 tablets of methaqualone. Both solid phase and liquid-liquid extractions were used in the extraction and clean-up of the samples. The total amount of methaqualone and its metabolites was measured by UV spectrophotometry. The amount of parent methaqualone was quantitated by GC/FID. Methaqualone and its 10 metabolites including two acetyl metabolites were found in urine and blood. This procedure is useful for monitoring drugs in emergency treatment. PMID- 7985520 TI - [Determination of mephenytoin and 4'-hydroxymephenytoin in urine by high performance liquid chromatography]. AB - A simple, sensitive and reproducible HPLC assay is described for the determination of mephenytoin and 4'-hydroxymephenytoin in human urine. Phenobarbital was used as an internal standard. The compounds were separated on a mu-Bondapack RP-C18 column using a mobile phase of acetonitrile-distilled water (40:60, v/v). The temperature of the column was maintained at 50 degrees C, and the UV detector was set at 210 nm. Calibration curves in the range 0.05-1.00 micrograms/ml for mephenytoin and 0.5-100.0 micrograms/ml for 4' hydroxymephenytoin were linear (r = 0.9998 and r = 0.9992, respectively). The average recovery was 95.10 +/- 2.95%, and the relative standard deviation within day and day to day was less than 10%. The detection limit for mephenytoin was 25 ng/ml and 4'-hydroxymephenytoin was 50 ng/ml. The method was used to study the metabolism of S-mephenytoin 4'-hydroxylatoin in 10 healthy volunteers. The 12 h urinary metabolic ratio (MR) and hydroxylation index (HI) were calculated to express interindividual variation in metabolism. Two of them exhibited defective 4'-hydroxylation of S-mephenytoin as poor metabolizers (HI: 1349.18 and 409.57; MR: 105.29 and 8.52). In the remaining 8 subjects, the HI ranged from 1.68 to 6.71 and the MR ranged from 0.002 to 0.015, as extensive metabolizers of S mephenytoin. PMID- 7985521 TI - [Gas chromatographic method with EC detection to determine isosorbide-5 mononitrate (IS-5-MN) in human serum and its pharmacokinetic parameters]. AB - A simple, sensitive and precise capillary GC-ECD method was developed for the determination of isosorbide-5-mononitrate in human serum. Pharmacokinetic parameters of the drug was obtained from the human serum level-time curve measured. Serum samples were extracted with a mixture of ethyl ether-ethyl acetate (4:1), the upper phase was collected and evaporated to about 100 microliters under a gentle nitrogen stream. Isosorbide dinitrate was used as internal standard. With a human serum sample size of 200 microliters, the detection limit of IS-5-MN was found to be about 5 ng/ml, and the absolute recovery from 74% to 85%. The within-day and between-day relative standard deviation were less than 7% and 9%, respectively. This method was applied to the pharmacokinetic studies of IS-5-MN tablets from two different sources. Two sets of t1/2 (Ke), Tmax and AUC values obtained from 8 volunteers were tested statistically and no significant difference was found. PMID- 7985522 TI - A test of an interruption/temporal-uncertainty theory of auditory backward recognition masking of target duration. AB - The present study examined auditory backward masking in a task requiring subjects to label a target sound as having a long or short duration. Perception of target duration was influenced by the interaction of the effects of (1) the similarity of the target/mask duration, (2) the acoustic similarity of the target and mask (tone vs. white noise), and (3) the interstimulus interval (ISI) between the target and mask. Specifically, relative to the long duration (100 ms) mask, the short duration (40 ms) mask helped performance for the target having a similar short duration (55 ms) but hurt performance for the target having a dissimilar long duration (85 ms). This effect of the similarity of target/mask duration was greater for acoustically similar targets and masks than for acoustically dissimilar targets and masks, and particularly so at the intermediate (45, 105, 165, 205 ms) ISIs. These results can be explained within the framework of Massaro and Idson's (1976) two-stage model by assuming that masking of perceived auditory duration is the result of two processes: (a) the mask's interruption of target processing in a peripheral auditory processing stage, and (b) a confusion of which item is the target vs. the mask, due to temporal uncertainty in the transfer of the target and mask into a central auditory processing stage. PMID- 7985523 TI - Women's deficiency in water-level representation: present in visual conditions yet absent in haptic contexts. AB - The present experiment studied horizontality representation among men and women performing the water-level task either in visual conditions (the subjects saw outlines of tilted containers in which they respectively drew or set the water line) or in partially and totally haptic conditions (respectively, the subjects both saw and felt or merely felt the contours of the containers cut out of metal plates, and positioned a rod on the underside of the plates to indicate the water line). It was expected that, as the visual components of the setting were replaced by haptic ones, a reduction of the typical gender difference in proficiency would ensue. It was found that men surpassed women under visual conditions, whereas both genders were equivalent in haptic conditions. There were no gender or condition differences in a control task in which a line had to be placed horizontally in tilted containers. Forced reliance on proprioceptive cues among both men and women under the totally haptic condition was contrasted with the critical role played in visual conditions by visual references; those used by men were correct, whereas the ones used by women were incorrect. PMID- 7985524 TI - Why do ambiguous figures reverse? AB - For much of this century the dominant theory of reversal of ambiguous figures has been neural satiation. We suggest a very different kind of theory based on the consequences of the typical instructions given to subjects in experiments on reversal. In analyzing these instructions in preliminary experiments we conclude that what matters is the subject's knowledge that the figure is reversible and specific knowledge of how its alternative construals appear. This leads to an intention to reverse the figure. In one experiment we demonstrate that recent experience with the ambiguous figure and its two modes of appearance does not lead to its reversal if the subject does not know the figure is reversible. In another experiment we demonstrate that when the subject does know the ambiguous figure is reversible, it nonetheless will not tend to reverse if the intention to do so is contravened by a different intention. We suggest that the intention to reverse cannot succeed unless the subject "knows" how to carry it out and, further, that the intention may become involuntary and automatic. PMID- 7985525 TI - The enhancement of iron-dependent luminol peroxidation by 2,2'-dipyridyl and nitrilotriacetate. AB - The generation of radicals from luminol and H2O2, in the presence of iron and iron chelates was monitored by measuring the chemiluminescence produced by further oxidation of these radicals. 2,2'-Dipyridyl enhanced the production of chemiluminescence in the presence of FeSO4, ferritin and haemosiderin but not FeCl3 or horseradish peroxidase. Nitrilotriacetic acid (NTA) enhanced chemiluminescence in the presence of both FeSO4 and FeCl3 but not ferritin or haemosiderin. The enhancement of chemiluminescence by iron chelation may have analytical applications and the process by which these iron chelates are able to generate radicals from the nitrogenous base luminol may be similar to that responsible for their toxic effects on DNA. PMID- 7985526 TI - Bioluminescent determination of 0.1 picomole amounts of guanine nucleotides. AB - A bioluminescence procedure for the determination of the guanylates has been optimized to allow measurement of 0.1 pmol amounts. Modifications of the Karl procedure include the use of purified firefly luciferase and nucleoside diphosphate kinase instead of a crude extract of firefly tails, the use of Tricine buffer instead of the inhibitory arsenate buffer, and optimization of the amounts of reagents and incubation times for each of the partial reactions. In the determination of GMP, background values varied widely with different lots of bovine guanylate kinase. Careful selection of a suitable lot of bovine brain guanylate kinase was essential for determination of lower amounts of guanylates. This establishes that selection of guanylate kinase must be based on experimental determination and not reported adenylate kinase activity. The wide variation in background was not eliminated by the inclusion of adenylate kinase inhibitors. PMID- 7985527 TI - Measurement of endogenous and TNF alpha-mediated H2O2 production in supernatants of SK-N-SH neuroblastoma cells with an enhanced chemiluminescence assay. AB - A sensitive peroxidase-dependent luminol-enhanced chemiluminescence (ECL) assay for determination of hydrogen peroxide (H2O2) generation by tumour cells was established. This test system allows determination of H2O2 in concentrations as low as 25 pmol (50 nmol/L) and yields results which are comparable to those obtained using a less sensitive photometric method and a previously described scopoletin fluorescence assay. After 3 h incubation time 10(4) SK-N-SH neuroblastoma cells released 60 +/- 5 pmol H2O2 in the supernatant and this level was significantly (p < 0.025) increased by about 70% in the presence of 5 pmol (100 ng/mL) recombinant tumour necrosis factor alpha (TNF alpha). In contrast, H2O2 production was slightly reduced by TNF alpha at a very low concentration of 0.5 fmol (0.01 ng/mL). PMID- 7985528 TI - Effect of oxygen abstraction on the peroxidase-luminol-perborate system: relevance to the HRP enhanced chemiluminescence mechanism. AB - Abstraction of oxygen from the HRP enhanced chemiluminescence system has no significant effect on the chemiluminescence generated. It is, therefore, proposed that in the peroxidase-luminol-perborate system at pH 7.3, chemiluminescence is generated by a direct reaction of diazaquinones with hydrogen peroxide and not, as generally assumed, from the reaction of luminol radicals with the molecular oxygen. PMID- 7985530 TI - Antigen and antibody molecular engineering in breast cancer diagnosis and treatment. 5th International workshop on breast cancer research and immunology. San Francisco, California, November 16-17, 1992. Proceedings. PMID- 7985529 TI - Characterization of peroxidases in luminol chemiluminescence coupled with copper catalysed oxidation of cysteamine. AB - Hydrogen peroxide formed during the course of the copper(II)-catalysed oxidation of cysteamine with oxygen was continuously determined by a peroxidase (POD) catalysed luminol chemiluminescence (CL) method. Horseradish peroxidase (HRP), lactoperoxidase (LPO) and Arthromyces ramosus peroxidase (ARP) were used as a CL catalyst. The respective PODs gave specific CL intensity-time profiles. HRP caused a CL delay, and ARP gave a time-response curve which followed the production rate of H2O2. LPO gave only a weak CL flash which decayed promptly. These differences of CL response curves could be explained in terms of the different reactivities of PODs for superoxide anion and the different formation rate of luminol radicals in the peroxidation of luminol catalysed by POD. PMID- 7985531 TI - Vaccination against breast cancer--studies in an animal model. PMID- 7985533 TI - The simultaneous expression of c-erbB-2 oncoprotein and laminin receptor on primary breast tumors has a predicting potential analogous to that of the lymph node status. PMID- 7985532 TI - Anti-idiotype antibodies as potential therapeutic agents for human breast cancer. PMID- 7985535 TI - The use of monoclonal antibody immunoconjugates in cancer therapy. PMID- 7985534 TI - Multivariate prognostic model for infiltrating ductal carcinoma of the breast in the axillary node-free patient. PMID- 7985536 TI - Does a novel form of the breast cancer marker protein, MUC1, act as a receptor molecule that modulates signal transduction? AB - Molecular analysis of a protein highly expressed in human breast cancer, indicates the presence of a polymorphic tandem repeat domain that encodes a conserved 20 amino acid repeat motif rich in serine and threonine residues that in the mature protein, designated MUC1, are linked via O-glycosidic linkages to sugar residues. Recent studies performed in our laboratory have led to the molecular characterization of a novel MUC1 repeat array minus mRNA, generated by an alternative splicing event that deletes the central tandem repeat array and its flanking sequences. The conceptually derived amino acid sequence of the novel MUC1 protein shows that it is identical with the previously reported transmembrane MUC1 amino acid sequence except for the deletion of the central 20 amino acid tandem repeat array and sequences immediately flanking the repeat array. This indicates that the novel MUC1 protein, which is devoid of the "hallmark" feature of mucins, the tandem repeat array, may be functionally different to the much larger, heavily glycosylated polymorphic repeat array containing MUC1 proteins, that affect cell-cell interactions. Based on an analysis of its peptide sequence, we propose the hypothesis that the novel MUC1 protein may act as a receptor molecule that modulates signal transduction. Preliminary experimental data supports this hypothesis. It appears, therefore, that the MUC1 gene is multifunctional with regard to its protein products- the repeat array containing MUC1 proteins may alter cellular adhesion processes whereas the novel MUC1 protein could be acting as a receptor-like molecule participating in signal transmission. PMID- 7985537 TI - Radioimmunolocalization of breast cancer using BrE-3 monoclonal antibody. PMID- 7985538 TI - Suppression of human anti-mouse antibody response to murine monoclonal antibody L6 by deoxyspergualin: a phase I study. PMID- 7985539 TI - Cancer metastasis determined by carbohydrate-mediated cell adhesion. PMID- 7985540 TI - Experimental immunotherapy of breast cancer using alpha interferon conjugated to monoclonal antibody Mc5. PMID- 7985541 TI - Circulating and tissue markers in the longitudinal management of breast cancer patients. PMID- 7985542 TI - Engineering of antibodies for breast cancer therapy: construction of chimeric and humanized versions of the murine monoclonal antibody BrE-3. PMID- 7985543 TI - Humanization of an anti-mucin antibody for breast and ovarian cancer therapy. AB - Antibody-drug conjugates utilize the targetting potential of antibodies to improve the potential of cytostatic or cytocidal drugs. One such murine monoclonal antibody, CTM01 (mCTM01), which recognizes an epitope on breast epithelial mucin, has potential for the treatment of breast and ovarian cancers. We examine in this paper the comparative properties of mCTM01 against a number of other anti-mucin antibodies. We then describe the humanization and high level re expression of humanized CTM01 (hCTM01), a process designed to avoid the immune response to administered murine antibodies in human patients and to produce sufficient material for clinical studies. We show that the humanized form has properties superior to mCTM01 in terms of binding affinity to antigen presented on tumour cells. PMID- 7985544 TI - Towards an immunotherapy for p185HER2 overexpressing tumors. PMID- 7985546 TI - Evaluating agency initiatives: building social science capability in tropical disease research. AB - In recent years, in an endeavour to increase social and economic research in tropical diseases, WHO/TDR has used a number of alternative models to develop social science research capability in countries endemic for the designated tropical diseases. These have included small grants schemes to encourage junior researchers to gain familiarity with the subject area and methods, and protocol development and methodology workshops, either for specific research topics (e.g. adolescent women's health; community perceptions of schistosomiasis) or for any topic of interest to the participants. Participants have included medical researchers, social science researchers, and interdisciplinary teams (e.g. a medical researcher and a collaborating social scientist). This paper develops a typology and critically analyses these alternative approaches to developing research capability, and assesses their effectiveness in terms of cost, short term effectiveness, and sustainability of the initiative. PMID- 7985545 TI - Branching N-linked oligosaccharides in breast cancer. AB - Tumor progression in rodent and human tumors is commonly associated with changes in glycoprotein glycosylation, in particular increased beta 1-6GlcNAc-branching, a regulatory step in expression of polylactosamine and extended-chain Lewis antigens. Loss of the branched oligosaccharides in murine tumor cells either due to somatic mutation, or treatment of the cells with the oligosaccharide processing inhibitor swainsonine, blocks tumor cells invasion in vitro and reduces solid tumor growth in vivo. Swainsonine and other inhibitors of N-linked oligosaccharide processing may be useful anti-cancer drugs, a premise which has begun to be tested in humans. PMID- 7985547 TI - Capacity building for health social science: the International Clinical Epidemiology Network (INCLEN) social science program and the International Forum for Social Science in Health (IFSSH). AB - This paper describes the unfolding of two complementary efforts to build global capacity in health social science. The INCLEN model aims to infuse a genuine transdisciplinary perspective into international health through equipping social scientists to speak a common language with clinical epidemiologists and sensitising clinicians to the ways social sciences contribute to research and policy. Issues are raised pertinent to the model's viability, including recruitment of scholars for fellowships, curriculum substance, and mechanisms for integrating social science fellows when they return home. The future success of the INCLEN program, and comparable donor initiatives, depends upon a wider infrastructure of career supports played out at the international level in which donor and operating agencies nourish the emergence of an expanded body of health social scientists. The International Forum for Social Sciences in Health (IFSSH) has been formed to help build this infrastructure and provide impetus for a viable scientific community of health social scientists. The IFSSH 'global agenda' is portrayed and an illustration is given of how this agenda is being implemented in the Asia and Pacific region. PMID- 7985548 TI - Institutional linkages: strategic bridges for research capacity strengthening. AB - The establishment and strengthening of research capacity in developing countries is of prime importance in empowering these countries to find rational and efficient solutions to their health problems through scientific research. Institutional linkages with other researchers in the North and South greatly facilitate the process of research strengthening through graduate study programs, technology transfer, 'hands-on' research training in the field, expanded networking with partners' contacts, and continued scientific exchanges in the context of actual research programs. This paper describes the experiences of the Research Institute for Tropical Medicine, the Philippines, in the area of research capacity development. Strengths and weaknesses of various approaches in institutional strengthening are discussed. PMID- 7985549 TI - Transdisciplinary research: research capacity building in developing countries at low cost. AB - Transdisciplinary research within the context of The Medical Research Council Programme on AIDS (MRCPA) has proven to be a way of research capacity building requiring relatively few additional costs. In developing countries where funds for specialised training are not always or easily available, encouraging multidisciplinary research teams is worthwhile, particularly for grooming into research relatively junior national researchers by providing them with opportunities to work with more senior international scientists. PMID- 7985550 TI - Developing health research capability in Tanzania: from a Swiss Tropical Institute Field Laboratory to the Ifakara Centre of the Tanzanian National Institute of Medical Research. AB - The paper summarizes the evolution of a biomedical field research station in Tanzania, established by a European institute, into a national health research and resource centre. The Swiss Tropical Institute Field Laboratory was founded in Ifakara in the Kilombero District in southeastern Tanzania in 1957. It has evolved into the Ifakara Centre, a national but peripherally located research centre involved in applied, operational and health systems research, training, and direct health sector support activities. Since 1991, the centre has been an affiliate of the National Institute for Medical Research in Tanzania. It has achieved an autonomous status and attracts frontline priority research and high quality research teams; the ongoing phase 3 malaria vaccine trial is a recent major activity. Starting from biomedical priorities in research and training, the centre has broadened its spectrum to include social science disciplines including economics. The major determinants for this development were (i) the long-term partnership between the executing agency in the north and the partners in the south at the national level, (ii) the support of this partnership by a long-term commitment of the major funding partners, (iii) the concept that local priorities form the basis of all activities, and (iv) the linking of research and training to public health action. The last two elements are considered to be crucial for the centre's multidisciplinary approach to health research and the support of public health in Tanzania and in eastern and southern Africa. PMID- 7985551 TI - Promoting interdisciplinary collaboration in health research in developing countries: lessons from the Triangle Programme in Sri Lanka. AB - The Triangle Programme (1989-1992) aimed at strengthening the institutional capacity for health social science research and intervention in Sri Lanka through the promotion of appropriate international and national partnerships. First, it involved an international partnership (Triangle 1) among two universities in the developed world, i.c. University of Antwerp in Belgium and the University of Connecticut in the USA, and one university in the developing world, i.c. the University of Peradeniya, Sri Lanka. This partnership facilitated the transfer of knowledge, experience, skills across national boundaries and the North/South divide. Second, it developed a national/local partnership (Triangle 2) among the Faculties of Arts, Agriculture and Medicine at the University of Peradeniya by involving them in a joint programme of health social science research and training covering the entire range of activities from proposal development to dissemination of research results. Focusing on the latter aspect (Triangle 2) this paper reviews the results of the programme from the angle of cross fertilization of disciplines through their collaboration in applied health research in a developing country setting. PMID- 7985552 TI - Reproductive health research in China: the Ford Foundation initiatives. AB - Increasing demographic and epidemiological evidence shows that maternal health problems are widespread and are linked to social, cultural, and economic factors, in particular, to women's status in society. Thus, there is an urgent need to expand existing knowledge about these influences on reproductive health and to empower women to gain control over them. To this end, there is a need for a comprehensive, interdisciplinary approach with an emphasis on social science research and training. The Ford Foundation, after an extensive review of its work in population and development, embarked on a new, ten-year, comprehensive reproductive health program for the 1990s. This paper describes one component of that program, a partnership with the All China Women's Federation to sponsor a series of reproductive health research activities. It examines the development and evaluates the positive and negative outcomes of the project, which commenced in 1991, from the perspective of a consultant involved in the process. So far, the project has generated interest in reproductive health in at least twenty-one Chinese provinces and has fostered a real partnership between the sponsoring and the collaborating agency. Based on the immediate outcomes of a research competition designed to identify research projects and investigators, of participant evaluation of the methodology training course, and of the strategies aimed at building capabilities and strengthening institutions in order to ensure future success, I conclude that the Ford Foundation's reproductive health initiative in China is a worthwhile and sustainable project. PMID- 7985553 TI - Setting up a scientific community by means of a small grants program: the Latin American experience. AB - The study of tropical diseases in Latin America has been dominated by the biomedical sciences, and whilst recently social science health research has been developed, there has been little collaboration between the two. The Latin American Small Grants Programme for Social and Economic Aspects of Tropical Diseases, launched by WHO/TDR in 1990, aimed to attract junior researchers into the area of social sciences and tropical diseases, and to create among them a scientific community. The program is unique in that it has involved the transfer of decision-making power from an international organisation (WHO/TDR) to a regional group. This article discusses the organisational structure of the program, the methods by which the program handled proposals, the evaluation process, the types of research proposals received, a profile of applicants, and the results of the applications. There was a balance of biomedical and social science applications. We conclude that the Small Grants Programme has been successful in fulfilling its objectives, due to the design of the grants scheme itself. PMID- 7985554 TI - Institutional constraints to building social science capability in public health research: a case study from Indonesia. AB - The promotion of social sciences capabilities in public health research in universities frequently encounters unexpected barriers. This paper argues that, in Indonesia, historic factors and institutional structures of public health research have created constraints to success in public health research and international technical assistance. Donors are often frustrated by apparent inconsistencies between agreed intentions and the subsequent behaviour of recipient colleagues, thus resulting in poor relations and failure of collaborative links. For social sciences to be integrated into public health research, assistance is needed in graduate education, library development, computerisation, and research methodology. Contributions in these areas may be ineffectual if they are not preceded or accompanied by efforts by recipients to reform or circumvent existing institutional weaknesses. Some important barriers to the development of research capabilities in Indonesia are beyond the control of individual faculties of public health, or even universities, and are affected by regulations and budgeting procedures of the National Department of Education and Culture, or the civil service administration. There are, however, changes that can be made at faculty or university level to encourage a more productive 'research culture' and promote linkages between the social and health sciences. PMID- 7985555 TI - Strengthening research capability, funding and sustainability: a personal perspective. AB - The need to strengthen research capability has led organizations to provide research-oriented training programs, including various short courses and protocol development workshops, at the end of which it is anticipated that the participants will be able to carry out the research work. However, to do research needs more than just training; it also requires funds, a research infrastructure, technical back-up and other support. This paper compares two of these programs from the perspective of an attendant: WHO/TDR's Fieldlincs program and the CAPS (Center for AIDS Prevention Studies) International Program. The paper also describes the experience of the approaches that have been used to get research funding. In addition, issues related to sustaining researchers in the field are discussed. PMID- 7985556 TI - Incorporating social sciences into health research. PMID- 7985557 TI - Neurologic complications of cerebral angiography. AB - PURPOSE: To examine the incidence of neurologic complications associated with modern cerebral angiography and to assess patient characteristics associated with an increased risk of complications. METHODS: One thousand consecutive cerebral angiographic procedures were evaluated prospectively. Examinations were performed using transfemoral catheterization and film-screen methods. For purposes of this trial, a neurologic complication was defined as any new focal neurologic deficit or change in mental status occurring during the angiogram or within the following 24 hours. Patients were evaluated during and at the completion of angiography. Follow-up evaluations were performed on the day of and the day after angiography. RESULTS: There were a total of 10 neurologic complications within 24 hours of angiography, 5 of which were persistent. Onset of 5 of the deficits occurred during angiography, the other 5 (3 persistent) were delayed. All complications occurred in patients being evaluated for stroke/transient ischemic attack or (in one case) asymptomatic bruit. A higher average age, longer average procedure time, and greater volume of radiographic contrast was noted in these patients than in the study population. CONCLUSION: Cerebral angiography was associated with a 1% overall incidence of neurologic deficit and a 0.5% incidence of persistent deficit. All complications occurred in patients presenting with a history of stroke/transient ischemic accident or carotid bruit, which may reflect the difficulty of performing angiography in this population at risk for atherosclerotic changes. PMID- 7985558 TI - Contrast enhancement of brain tumors at different MR field strengths: comparison of 0.5 T and 2.0 T. AB - PURPOSE: To compare the degree of MR contrast enhancement of 0.5 T and 2.0 T in various brain tumors. METHODS: MR images were studied prospectively in each of 31 patients with brain tumors (11 gliomas, 6 meningiomas, 6 neurinomas, and 8 others) before and after intravenous injection of gadopentetate dimeglumine. In every patient, both 0.5-T and 2.0-T MR studies were done within 1 week. Each patient received an initial standard dose (0.1 mmol/kg) of gadopentetate dimeglumine, followed by a subsequent 0.1-mmol/kg dose (total, double dose) in MR of each field strength. MR was done before and after each injection of the contrast agent. Degree of contrast enhancement in the lesions was assessed both visually and quantitatively. RESULTS: With standard-dose study, the tumor enhancement was visually stronger at 2.0 T than at 0.5 T in 9 gliomas. In extraaxial tumors there was visually no or minimal difference between 0.5 T and 2.0 T. Overall mean contrast-enhancement ratio and tumor and brain contrast-to noise ratio were higher at 2.0 T than at 0.5 T by 53% and 108%, respectively. The double-dose study showed higher contrast-enhancement ratio and contrast-to-noise ratio than the standard-dose study at both field strengths, and the differences between 0.5 T and 2.0 T were almost similar to those of the standard-dose study. The degree of contrast enhancement with the standard dose at 2.0 T was comparable to that of the double dose at 0.5 T in most intraaxial tumors. CONCLUSION: The results suggest that effect of contrast enhancement increases with the field strength. Therefore, reevaluation of optimal doses of contrast media may be needed in a variety of brain lesions at each field strength. PMID- 7985559 TI - Postoperative evaluation for intracranial recurrence of medulloblastoma: MR findings with gadopentetate dimeglumine. AB - PURPOSE: To characterize the gadopentetate dimeglumine-enhanced MR features of recurrent medulloblastoma. METHODS: The postsurgical gadopentetate dimeglumine enhanced MR images of 48 patients (206 head examinations) with prior resection of medulloblastoma were retrospectively evaluated for enhancement in the brain parenchyma, meninges (dura, pia-arachnoid), and ventricles. RESULTS: Nineteen patients had recurrent tumor as determined by clinical course and positive imaging studies. Seventeen patients with recurrent disease had intracranial enhancement predominating in the pia-arachnoid (63%) or as a focal nodular brain lesion (26%). Three of these patients also had intraventricular metastases. None of the clinically healthy patients had these findings. One patient had recurrent tumor presenting within the fourth ventricle. Only 3 of 8 intraventricular lesions observed in the 4 patients initially enhanced with gadopentetate dimeglumine. Another patient with recurrent disease had extensive skeletal metastases without involvement of the central nervous system. Dural enhancement was observed in patients both with (42%) and without (38%) recurrent tumor. CONCLUSION: The MR findings of pia-arachnoidal or focal nodular brain enhancement are highly specific in the diagnosis of recurrent medulloblastoma. Pia arachnoidal or focal brain enhancement were also the most frequent patterns associated with recurrent tumor. Dural enhancement alone is not a reliable indicator of recurrent medulloblastoma. Not all intraventricular metastases enhance with gadopentetate dimeglumine, and careful evaluation for nonenhancing lesions within the ventricles should be made on postoperative MR examinations. PMID- 7985560 TI - Germinoma originating in the basal ganglia and thalamus: MR and CT evaluation. AB - PURPOSE: To describe MR and CT features of germinoma originating in the basal ganglia and thalamus and to discuss the roles of each modality for its diagnosis. METHODS: MR and CT studies of six cases of germinomas, five of which were histologically proved, were retrospectively reviewed. T1-weighted, T2-weighted, and contrast-enhanced T1-weighted conventional spin-echo images, and unenhanced and contrast-enhanced CT images were evaluated. RESULTS: Typically, the tumor consisted of an irregular solid area with contrast enhancement and various-size cysts. Cystic components were found in five cases and calcification in four. Intratumoral hemorrhage was noted in one. Ipsilateral cerebral hemiatrophy and brain stem hemiatrophy were noted in three cases each. MR was superior to CT in evaluating precise tumor extension, cystic components, and intratumoral hemorrhage, although in one case, extension of the tumor was better defined on CT in its early stage. Calcification was difficult to identify by MR alone. The solid components of the tumors generally showed slightly high density on CT, which seemed to be characteristic compared with nonspecific intensity pattern on MR. CONCLUSION: The combination of CT and MR findings allows early detection and appropriate diagnosis of the mass in the basal ganglia and/or thalamus. PMID- 7985561 TI - Early differential diagnosis of infantile neuronal ceroid lipofuscinosis, Rett syndrome, and Krabbe disease by CT and MR. AB - PURPOSE: To compare early radiologic findings in three clinically similar progressive encephalopathies of childhood. METHODS: Brain CT and/or MR studies were done in 57 children 3 to 36 months of age: 16 with infantile neuronal ceroid lipofuscinosis, 5 with Rett syndrome, 6 with Krabbe disease, and 30 control subjects with normal neurologic status. In addition, previous descriptions in the literature were collected. RESULTS: No significant changes were seen in Rett syndrome. Early atrophy was found in infantile neuronal ceroid lipofuscinosis and in Krabbe disease, being more severe in the latter. The thalami were hyperdense in 4 of 13 patients with infantile neuronal ceroid lipofuscinosis and in 1 of 4 patients with Krabbe disease (in the literature in 12 of 30 examinations). Cerebral calcifications and density abnormalities in the cerebral and cerebellar white matter were seen in Krabbe disease only. On MR, the white matter changes in the two diseases were differently located. In every patient with infantile neuronal ceroid lipofuscinosis, decreased T2 signal was seen in the thalami and periventricular high-signal rims after the age of 13 months. Hypointensity of the thalami and basal ganglia was seen in both diseases, but Krabbe disease showed more variations. Abnormalities of cerebellar intensity were found in Krabbe disease only. CONCLUSIONS: CT and MR are of value in the differential diagnosis of these three diseases. MR especially facilitates the early diagnosis of infantile neuronal ceroid lipofuscinosis. PMID- 7985562 TI - Early infantile form of Krabbe disease with optic hypertrophy: serial MR examinations and autopsy correlation. AB - The development of white matter lesions in a case of autopsy-proved early infantile form of Krabbe disease was monitored by serial MR examinations. Hypertrophy of the optic nerves was present late in the course of the patient's disease and is a remarkable feature in this case. PMID- 7985563 TI - CT and MR of the brain in disorders of the propionate and methylmalonate metabolism. AB - PURPOSE: To present the CT and MR findings in children with propionic and methylmalonic acidemia. METHODS: Twenty-three new patients with methylmalonic and 20 with propionic acidemia were examined with CT and/or MR of the brain. In total 52 CT and 55 MR studies were done. Twenty-six previously published cases were also reviewed. RESULTS: The findings were similar in the two syndromes. During the first month of life the examinations were either normal or showed white matter attenuation. Later during the first year moderate or even severe widening of sulci and fissures was seen, especially in infants with propionic acidemia. During therapy, these changes often resolved, especially in the patients with methylmalonic acidemia. Mild to moderate delay in myelination was also a common finding in both disorders. Basal ganglia changes, predominately in the globus pallidus, were seen in five patients with methylmalonic acidemia and in two children with propionic acidemia; in two patients these changes were transient. CONCLUSION: Children who have methylmalonic or propionic acidemia, in addition to widening of cerebrospinal fluid spaces and some delay in myelination, also often show symmetric involvement of the basal ganglia. PMID- 7985564 TI - CT and MR of 3-hydroxy-3-methylglutaryl-coenzyme A lyase deficiency. AB - Siblings with 3-hydroxy-3-methylglutaryl-coenzyme A lyase deficiency were evaluated with CT and MR. Both imaging studies demonstrated a leukodystrophy with preferential involvement of the deeper arcuate fibers. PMID- 7985565 TI - Neonatal hypoglycemia: CT and MR findings. AB - A case of neonatal hypoglycemia with extensive occipital cortical loss is presented. Imaging studies revealed a predominance of brain parenchymal loss in the occipital lobes bilaterally with nearly complete absence of cortex in the posterior parietal and occipital regions and generalized thinning of the cortex throughout the brain. PMID- 7985566 TI - Hemimegalencephaly: a longitudinal MR study. AB - An infant with hemimegalencephaly was studied with MR at 5 days and again at 10 months of age. The initial scan showed an abnormally large left cerebral hemisphere. At the age of 10 months, the left cerebral hemisphere was smaller than the right--an apparent left-sided micrencephaly caused by normal growth of the right hemisphere and arrested growth of the left. The age of imaging of a patient with hemimegalencephaly can be important if the correct diagnosis is to be made. PMID- 7985567 TI - Neonatal pontomedullary disconnection with aplasia or destruction of the lower brain stem: a case of pontoneocerebellar hypoplasia? AB - We report a neonate who presented with marked hypotonia and absent suck reflex. MR demonstrated complete absence of the pons as well as absence of a basilar artery flow void. Our case exhibits features similar to those described in previous reports of pontoneocerebellar hypoplasia, but with a more severe degree of pontine involvement. The associated vascular findings suggest a vascular insult to the brain stem as the cause. PMID- 7985568 TI - Vein of Galen aneurysms: a review and current perspective. AB - Our approach to treating a patient with a vein of Galen aneurysm is, of course, influenced greatly by the age of the patient, the clinical symptoms, and the angiographic architecture of the malformation. Therapeutic options are primarily based on whether a true AVM is present or if the malformation represents an arteriovenous fistula involving the vein of Galen. Arterial endovascular approaches, microneurosurgery, and/or radiosurgery are preferred for management of the former; the transvenous endovascular approach has become the cornerstone of treatment in the latter. The most critical group, however, is the neonates in extreme cardiovascular distress. In this case our therapeutic intervention is initially endovascular from the venous side, either transfemoral or transtorcular. The immediate goal is to increase resistance to right ventricular output. Advantages of this approach over a transarterial approach include a shorter anesthesia time, minimal fluid and/or contrast administration, and creation of a wire "basket" or "bird's nest" on the venous side that helps prevent emboli that may be deposited on the arterial side in subsequent embolizations from passing through the malformation. The transvenous approach can be easily repeated multiple times and may be supplemented by transarterial embolizations. Endovascular coils have been the mainstay for such venous embolizations. The end point of treatment is not complete occlusion of the fistula but improvement in cardiac function. Often, more than one stage is required to reach our goal. The results in recent years have been encouraging and are to a large degree attributable to the advances in endovascular approaches. With future improved tools for diagnosis and treatment, perhaps the prognosis for this difficult malady also will continue to improve. PMID- 7985569 TI - The magnetization transfer effect in cerebral infarction. AB - PURPOSE: To estimate the age of cerebral infarcts using magnetization transfer. METHODS: Twelve patients with radiographically and clinically documented cortical and subcortical cerebral infarctions underwent MR imaging on a 0.1T magnet. Magnetization transfer contrast images were generated by application of off resonance pulses to every other repetition time on intermediate-weighted images. The magnetization transfer effect was calculated by obtaining an intensity value in the region of interest within the infarcted area. RESULTS: The data show a pattern in which the magnetization transfer effect decreases as the chronicity of the infarct increases. Infarcts less than 1 week old had an average magnetization transfer effect of 0.35. Those more than 1 week and less than 1 month old average 0.30. Infarcts more than 1 month and specifically those more than 1 year old averaged 0.16 or less. CONCLUSION: Magnetization transfer offers the potential to estimate the age of cerebral infarcts. PMID- 7985570 TI - Venous congestion: an MR finding in dural arteriovenous malformations with cortical venous drainage. AB - PURPOSE: To present the MR findings of intracranial dural arteriovenous malformations with cortical venous drainage, emphasizing the parenchymal changes. METHODS: Conventional MR and x-ray angiograms in 13 patients with dural arteriovenous malformations and cortical venous reflux were reviewed. The site of the shunt, location of the venous reflux, and presence of venous stenosis were assessed on the angiograms. Parenchymal changes, dilated vessels, and venous occlusive disease were assessed on MR. RESULTS: On MR, 10 of the 13 patients (77%) had dilated pial vessels. Two patients had hydrocephalus. Two patients presented with parenchymal bleeds, one with a subdural component, both remote from the nidus. Two patients presented with subarachnoid hemorrhage. One patient had a parenchymal bleed 9 months after presentation. Venous occlusion was evident on MR in 2 patients. Diffuse white matter edema in the cerebellar or cerebral hemispheres was present on MR in 4 patients and correlated with neurologic deficits. In 2 of these 4 patients, gadolinium enhancement was seen in the periphery of the involved hemisphere. CONCLUSIONS: On MR a surplus of pial vessels suggests a dural arteriovenous malformation with cortical venous drainage. The MR finding of white matter edema deep in the cerebral or cerebellar hemispheres is direct evidence of a venous congestion. PMID- 7985571 TI - Radiologic-clinical correlation. Isolated third nerve palsy caused by midbrain hemorrhage. PMID- 7985572 TI - Neurofibromatosis type 1: the evolution of deep gray and white matter MR abnormalities. AB - PURPOSE: To investigate the evolution of deeply located high-signal-intensity abnormalities of the brain on T2-weighted MR images of patients with neurofibromatosis type 1 (NF-1). METHODS: The study consists of two patient groups: 1) retrospective evaluation of MR scans of 24 symptomatic NF-1 patients, 10 of whom were sequentially studied, and 2) prospective MR evaluations of 20 asymptomatic NF-1 subjects from 14 families; 2 of these families were sequentially studied. RESULTS: Deeply located, high-signal-intensity abnormalities on T2-weighted images were noted in 34 of 44 NF-1 subjects (77%). If NF-1 patients are grouped according to age, 28 of 30 subjects (93%) younger than 15 years had the lesions, whereas 4 of 7 subjects (57%) between 16 and 30 years, and 2 of 7 subjects (29%) older than 31 years had lesions. High-signal lesions in basal ganglia and brain stem were demonstrated in all decades with relatively high frequency. Lesions in the cerebellar white matter and dentate nuclei were mainly found in the patients younger than 10 years, and never found after the third decade. In 13 sequential studies (mean interval, 24 months), lesions appeared to increase in size in 3, remain unchanged in size in 2, and decrease in size in 7. One subject showed a mixed pattern of lesion size change. CONCLUSIONS: Deeply located high-signal-intensity lesions on T2-weighted MR images are more evident in young NF-1 patients. The underlying brain abnormality, while pathologically unproved, is probably transient. PMID- 7985573 TI - Incontinentia pigmenti: MR demonstration of brain changes. AB - PURPOSE: To describe the MR findings in eight girls and women with incontinentia pigmenti, from two families. Four had skin lesions and neurologic disease, and four had only skin lesions. METHODS: Eight patients had physical examination, family history, electroencephalogram and MR examination of the brain. MR was repeated in the two cases with more severe changes several years after the first study. RESULTS: MR revealed brain changes only in the four patients who had neurologic disease associated with the cutaneous lesions of incontinentia pigmenti. Abnormalities were located in the cerebral hemisphere contralateral to the most affected side of the body. In two cases, the MR changes were subjacent to the scalp areas where the most severe cutaneous lesions were located in the neonatal period. Hypoplasia of the corpus callosum, probably secondary to atrophy of one or both cerebral hemispheres, and abnormal signal and atrophy of the lateral regions of one of the cerebellar hemispheres also were found in all four cases. Although the changes were seen in both the T1- and T2-weighted images, they were most evident in the latter. The four patients in the fourth stage who had only cutaneous lesions without neurologic problems did not reveal any MR abnormalities. CONCLUSIONS: This study demonstrates MR signal changes and focal atrophy of the cerebrum, cerebellum, and corpus callosum in patients with incontinentia pigmenti and neurologic disorders. The MR images appear normal in patients with incontinentia pigmenti who have no neurologic abnormalities. PMID- 7985574 TI - Potential toxic effects of superselective injection of amobarbital sodium on microvasculature: a study in an animal model. AB - PURPOSE: To determine whether microvascular damage occurs from superselective intraarterial injection of amobarbital sodium using the swine endovascular embolization model. METHODS: Thirty-four swine underwent percutaneous femoral puncture for superselective catheterization of the proximal artery of the rete. Varying concentrations of amobarbital sodium were prepared (12.5 to 100 mg/mL solution) in either normal saline or sterile water (105 mOsm/L to 1138 mOsm/L) of which one concentration was infused slowly into one ipsilateral rete. Control infusions were also performed. Histopathologic changes were evaluated at 30 minutes and 10 days after infusion, using standard light and electron microscopy techniques. RESULTS: Moderate vasospasm occurred only in three swine at 100 mg/mL amobarbital sodium in normal saline. Light microscopy showed no significant histologic changes in the retia at any of the tested concentrations of amobarbital sodium. Electron microscopy showed ultrastructural alterations in the intima only at the higher amobarbital sodium concentrations. CONCLUSIONS: Concerns for inducing significant damage to cerebral microvasculature by superselective injection of amobarbital sodium at the usually recommended concentrations and doses are probably not justified. PMID- 7985575 TI - An experimental arteriovenous malformation model in swine: anatomic basis and construction technique. AB - We assessed the feasibility of creating an experimental arteriovenous malformation model in swine by diverting and increasing blood flow through bilateral retia mirabilia. This was achieved by surgical formation of a large right-sided carotid-jugular fistula, in combination with endovascular occlusion of several neck arteries ipsilateral to the fistula. Using this technique, 11 of 13 swine demonstrated an acute-phase angiographic simulation of an arteriovenous malformation. There was rapid circulatory diversion from the left ascending pharyngeal artery ("feeder"), across both retia ("nidus"), and fast retrograde flow into the right ascending pharyngeal and common carotid arteries ("draining vein") toward the fistula. The relevant vascular anatomy of the swine head and neck is outlined, and steps in the construction of this arteriovenous malformation model are detailed. PMID- 7985577 TI - Short versus long echo time for cranial MR angiography in children and adults. AB - PURPOSE: To evaluate the ability of short-echo-time (TE) versus long-TE three dimensional time-of-flight MR angiography sequences to decrease phase-related signal loss and refocus signal from blood in intracranial MR angiography of adults and children. METHODS: We evaluated 3-D time-of-flight cranial MR angiography in 33 cases (18 children and 15 adults) using two sequences. The longer-echo reference sequence had a TE of 8.0 milliseconds and a field echo of 6.5 milliseconds; the shorter-echo sequence had a TE of 5.1 and a field echo of 4.2 milliseconds. Repetition time, flip angle, and matrix were constant. The bandwidth for the longer-echo sequence was 130 Hz, 195 Hz for the shorter-echo sequence. RESULTS: The greatest improvement in diagnostic images was for children; significant and mildly improved signal recovery was demonstrated in 15 and 2 cases, respectively, of a total of 18 studies. This allowed improved diagnostic assessment. However, in the adult group significantly and mildly improved signal recovery were present in only 2 and 6 cases, respectively, of a total of 15 studies. In the group of children and adults combined, decreased lumen definition and peripheral vessel visibility were present in 24 and 30 of 33 cases, respectively, because of higher signal from background tissue when the shorter-TE field-echo sequence was used and, hence, reduced vascular contrast. CONCLUSION: The use of a short-field-echo/TE sequence is therefore recommended as the initial study in children but as a secondary examination in areas of abnormality in adults. This study illustrates the improved signal recovery from phase-related sources and improved visibility of intracranial stenosis in children with the use of a short-echo sequence. In adults, the short-echo sequence should not be used for the initial screening but reserved for secondary evaluation. PMID- 7985576 TI - Temporal lobe epilepsy: the various MR appearances of histologically proven mesial temporal sclerosis. AB - PURPOSE: To determine the frequency of appearance of various MR signs in mesial temporal sclerosis, to determine the optimal scanning planes for their visualization, and to propose a histologic explanation for the diminished demarcation between gray and white matter in the temporal lobe, a frequent MR finding in patients with mesial temporal sclerosis. METHODS: MR scans of 14 surgically treated patients with epilepsy and histologically proven mesial temporal sclerosis were assessed for the presence of six features: feature 1, high signal intensity in the hippocampus; 2, reduced hippocampal size; 3, ipsilateral atrophy of the hippocampal collateral white matter; 4, enlarged temporal horn; 5, reduced gray-white matter demarcation in the temporal lobe; and 6, decreased temporal lobe size. RESULTS: Feature 1 was present in 14 patients and was best appreciated on the T2-weighted images in planes parallel to the long axes of the hippocampi. Feature 2, present in 12 patients, and feature 6, present in 9 patients, were optimally seen in the coronal planes and on the inversion recovery sequences in particular. Feature 3, present in 12 patients, was optimally seen on the coronal T2-weighted images. Feature 4, seen in 11 patients, was equally well seen in all planes (transverse, coronal, and parallel to the long axes of the hippocampi). Feature 5, seen in 10 patients, was best appreciated on the T2-weighted images in the planes of the long axes of the hippocampi. Histologic investigation of the temporal lobe white matter in the 10 patients with feature 5 demonstrated on the MR scan showed abnormalities in 7 cases. Oligodendroglia cell clusters were found in 6, with concomitant corpora amylacea in 1 case and perivascular macrophages with pigment a sole finding in another case. CONCLUSION: Of the six features found in cases of mesial temporal sclerosis on MR, increased hippocampal signal intensity is the most consistent. A decreased gray-white matter demarcation in the temporal lobe parenchyma is also a frequent feature of this disease. A combination of multiple scanning planes results in an optimal demonstration of lesions. PMID- 7985578 TI - Words and things: paradigms lost or never found. PMID- 7985579 TI - Magnetization transfer: a potential method to determine the age of multiple sclerosis lesions. AB - PURPOSE: To determine whether magnetization transfer contrast can differentiate acute from chronic lesions in multiple sclerosis. METHODS: Thirteen patients with multiple sclerosis and eight healthy patients were studied with MR using a 0.1-T system. Relatively T2-weighted spin-echo images were obtained without and with magnetization transfer contrast. The magnetization transfer effect of multiple sclerosis lesions was calculated and compared with the ages of the lesions. The magnetization transfer effect of normal-appearing white matter in patients with multiple sclerosis was calculated and compared with the magnetization transfer effect of white matter in healthy volunteers. Statistical analysis was performed. RESULTS: White matter in the healthy volunteers had values from 0.40 to 0.45. Normal-appearing white matter in the patients with multiple sclerosis had magnetization transfer effect values ranging from 0.41 to 0.45. Multiple sclerosis plaques of less than 1 year's duration had magnetization transfer effect values ranging from 0.05 to 0.26; older plaques had values from 0.25 to 0.41. The difference in the distributions of these values for acute and chronic multiple sclerosis plaques is statistically significant. CONCLUSION: Current imaging modalities do not differentiate acute multiple sclerosis lesions from chronic ones. Our data on magnetization transfer show a statistically significant difference in magnetization transfer effect values between lesions of less than 1 year's duration and older lesions. The different values may correspond to the histologic changes of multiple sclerosis plaques over time. Magnetization transfer may be a reliable method for determining the age of multiple sclerosis lesions. PMID- 7985580 TI - MR findings in seven patients with organic mercury poisoning (Minamata disease). AB - PURPOSE: To study the long-term MR findings in seven patients with Minamata disease. METHODS: All patients examined were affected after eating daily considerable amounts of the methylmercury-contaminated seafoods from 1955 through 1958 and showed typical neurologic findings. T1- and T2-weighted images were obtained in axial, coronal, and sagittal sections. RESULTS: The visual cortex, the cerebellar vermis and hemispheres, and the postcentral cortex were significantly atrophic. The visual cortex was slightly hypointense on T1-weighted images and hyperintense on T2-weighted images, probably representing the pathologic changes of status spongiosus. CONCLUSION: MR demonstrated the lesions, located in the calcarine area, cerebellum, and postcentral gyri, which are probably related to three of the characteristic manifestations of this disease: the constriction of the visual fields, ataxia, and sensory disturbance, respectively. PMID- 7985581 TI - Spiral CT of the larynx. AB - PURPOSE: To compare conventional and spiral CT studies of the larynx. METHODS: Ten patients had both conventional and spiral CT studies of the neck using 5-mm section collimation and 5-mm increments. The spiral scans also were reconstructed at 2-mm increments. Five patients had two spiral CT larynx studies with 5-mm and 2-mm collimation. Two observers independently rated the visibility of laryngeal structures and absence of motion artifact in the studies and assigned values from 1 (poor) to 4 (excellent). RESULTS: The spiral scan images showed less motion artifact (1.9 versus 3.6) and better anatomic detail (2.3 versus approximately 2.6). Thinner reconstruction intervals and sections gave better anatomic detail (2.3 versus approximately 3.3). Interobserver kappa was 0.65. CONCLUSION: Spiral is better than conventional CT scanning when studying the larynx. PMID- 7985583 TI - Just the artifacts, ma'am. PMID- 7985582 TI - Prevalence of MR evidence of diffuse axonal injury in patients with mild head injury and normal head CT findings. AB - PURPOSE: To assess the prevalence of MR evidence for diffuse axonal injury at 1.5 T in patients with normal head CT findings after mild head injury. METHODS: Twenty consecutive patients with mild head injury (Glasgow Coma Scale, 13 to 15; no subsequent deterioration, loss of consciousness < 20 minutes) and normal head CT findings were examined with MR at 1.5 T. Pulse sequences included a conventional T2-weighted spin-echo sequence (2500-3000/30,80/1[repetition time/echo time/excitations]) and a T2*-weighted gradient-echo sequence (750/40/2, 10 degrees flip angle). Each sequence was read independently by two blinded readers. RESULTS: The readers agreed that abnormalities compatible with diffuse axonal injury were present in the white matter of 6 (30%) of 20 patients (95% confidence interval, 12% to 54%). Both readers agreed that foci of high signal intensity were present on the T2-weighted spin-echo sequence in 3 (15%) of the 20 cases (95% confidence interval, 3% to 38%) and that foci of hypointensity compatible with hemorrhagic shear injury were present on the T2*-weighted sequence in 4 (20%) of the 20 patients (95% confidence interval, 6% to 44%). Both types of abnormality were noted by the readers in one patient. CONCLUSIONS: MR shows evidence of diffuse axonal injury in some patients with normal head CT findings after mild head injury. These lesions may represent the pathologic substrate underlying the postconcussion syndrome that occurs in many patients with moderate to severe head injury. PMID- 7985584 TI - MR of corticotropin-secreting pituitary microadenomas. AB - PURPOSE: To assess the accuracy of MR in the preoperative identification of corticotropin-secreting pituitary microadenomas. METHODS: Twenty-six patients with clinical and biochemical evidence of pituitary-driven Cushing disease in whom MR of the seller region was performed were selected for this study. The MR examinations were retrospectively evaluated by a neuroradiologist who was aware of the presence of an adenoma at surgery but not of location and size of the lesion. RESULTS: Considering the whole group of MR examinations performed either without (n = 26) or without and with intravenous injection of gadopentetate dimeglumine (n = 16), overall 20 MR studies were judged to show disease. Seventeen of 26 microadenomas were adequately shown and located by MR (true positive, 65.4%). In three cases the sides of the microadenomas were misjudged (false-positive, 11.5%). Six patients had negative MR studies (false-negative, 23%). Twelve of the 16 patients studied after gadopentetate dimeglumine injection had true-positive MR findings (75%). CONCLUSIONS: In our experience the accuracy of MR in detecting corticotropin-secreting microadenomas as small as 2 to 3 mm is 65% to 75%. Although precontrast images provide diagnostic information, the microadenoma can be better seen with administration of contrast material. PMID- 7985585 TI - Annotated bibliography. PMID- 7985586 TI - Pharmacologic stress dual-isotope myocardial perfusion single-photon emission computed tomography. AB - Separate-acquisition rest thallium-201/exercise technetium-99m sestamibi (sestamibi) dual-isotope single-photon emission computed tomography (SPECT) has been shown to be effective for assessment of myocardial perfusion and viability. The present study was designed to validate the dual-isotope approach when used in conjunction with pharmacologic stress. All patients had rest 201TI SPECT followed immediately by adenosine (n = 82) or dipyridamole (n = 50) infusion and sestamibi injection. Sestamibi SPECT was performed 1 hour later. The entire study lasted < 2.5 hours. The patient population was categorized into three groups: 51 consecutive patients with coronary angiography and no previous myocardial infarction (group I), 58 consecutive patients with a low prescintigraphic test likelihood of coronary artery disease (group II), and 23 consecutive catheterized patients with remote Q-wave myocardial infarction (group III). For group I patients, the sensitivity and specificity for dual-isotope SPECT were 92% (35 of 38) and 85% (11 of 13), respectively, when > or = 50% coronary artery narrowing was considered significant and were 97% (34 of 35) and 81% (13 of 16) respectively, when > or = 70% narrowing was considered significant. The normalcy rate among the 58 patients of group II was 96%. Comparisons for pattern of stress defect reversibility demonstrated that of the 97 stress defects within the infarct zones (group III), 15% were reversible and 85% were nonreversible. In contrast, of the 227 stress defects within the diseased (> or = 50% stenosis) vessel zones of the group I patients, 93% were reversible and 7% were noreversible (p < 0.001 vs group III). In conclusion, separate acquisition rest 201-TI/pharmacologic stress sestamibi dual-isotope SPECT is an efficient myocardial perfusion imaging protocol with high accuracy for detection and assessment of angiographically significant coronary artery disease. PMID- 7985587 TI - Effect of angiographic and hemodynamic results of coronary balloon angioplasty on late angiographic outcome. AB - A small residual stenosis and a low residual translesional pressure gradient after percutaneous transluminal coronary angioplasty (PTCA) are thought to be associated with lower rates of restenosis. However, these two posprocedure parameters have not been studied simultaneously in relation to late angiographic outcome. Restudy angiograms after successful single-vessel and single-lesion PTCA were performed in 1261 patients, who were divided into three groups according to final residual stenosis: group 1, 0% to 19%, group 2, 20% to 34%, and group 3, 35% to 49%. This study population also was divided into two groups by final residual pressure gradient: < or = 17 and > or = 18 mm Hg. Luminal patency at restudy and restenosis rates by these definitions were studied. By the definition of > or = 50% stenosis at restudy, group 1 had the lowest restenosis rate, and group 3 had the highest. By the definition of an increase of > or = 30% stenosis compared with the immediate post-PTCA result, group 1 had the highest restenosis rate, and group 3 had the lowest. Although it had the greatest loss of luminal diameter over the follow-up period, group 1 maintained the greatest luminal patency at restudy. A residual pressure gradient < or = 17 mm Hg was associated with lower restenosis rate regardless of the definition used. Despite greater loss of luminal diameter over the follow-up period, optimal postprocedure angiographic results may result in better long-term luminal patency. Transluminal pressure gradient is more predictive of late angiographic results regardless of the definition used. Further studies, with hemodynamic measurements, may reveal potential clinical implications. PMID- 7985588 TI - Impairment of myocardial vascular responsiveness after transient myocardial ischemia and reperfusion. AB - Coronary vascular responses after brief periods of myocardial ischemia are impaired. Whereas some studies suggest that the ischemic insult selectively depresses endothelium-dependent vasodilator mechanisms, other studies indicate that even responses to direct vascular smooth-muscle relaxants such as adenosine may be decreased. This study was undertaken to measure regional myocardial blood flow (RMBF) responses to adenosine (a direct coronary vasodilator) and serotonin (an indirect, endothelium-dependent vasodilator) in myocardium subjected to regional ischemia followed by reperfusion. Temporary regional ischemia was achieved by 20 minutes of occlusion of the left anterior descending coronary artery (LAD) followed by 20 minutes of reflow in 10 open-chest anesthetized dogs. In the left circumflex coronary artery (LCX) territory, which served as a nonischemic control, RMBF (measured with radioactive microspheres) increased significantly in response to left atrial infusions of adenosine (1.29 +/- 0.27 to 3.89 +/- 3.89 +/- 2.15 ml/min/gm; p < 0.001) and serotonin (1.29 +/- 0.27 to 3.29 +/- 1.49 ml/min/gm; p < 0.001) and the percent reduction in coronary vascular resistance (% delta CVR) was comparable for these two pharmacologic probes (65% +/- 26% vs 62% +/- 19%; difference not significant [NS]). In contrast, in the myocardium supplied by the LAD, which was subjected to ischemia followed by reperfusion, the augmentation of RMBF by adenosine (1.07 +/- 0.29 to 1.82 +/- 1.35 ml/min/gm; p < 0.001) and serotonin (1.07 +/- 0.29 to 2.37 +/- 1.21 ml/min/gm; p < 0.001) was blunted.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7985589 TI - Suppression of hyperventilation-induced attacks with infusion of B-type (brain) natriuretic peptide in patients with variant angina. AB - B-type (brain) natriuretic peptide (BNP) forms a peptide family with A-type (atrial) natriuretic peptide (ANP), which is involved in the regulation of blood pressure and fluid volume. We have demonstrated that BNP is a novel cardiac hormone secreted predominantly from the ventricle and that plasma levels of BNP markedly increase in proportion to the severity of congestive heart failure. Spasm of a major coronary artery (coronary spasm) is the cause of variant angina and can be induced by hyperventilation. We examined whether BNP infusion suppresses coronary spasm in patients with variant angina. The effect of BNP infusion on anginal attacks induced by hyperventilation was studied in 11 patients with variant angina in whom the attacks were reproducibly induced by hyperventilation. This study was performed in the early morning on 3 consecutive days. Fourteen minutes after infusion of BNP was begun (day 2, 0.05 micrograms/kg/min) or saline (days 1 and 3), hyperventilation was started and continued for 6 minutes. Anginal attacks were induced in all 11 patients by hyperventilation on days 1 and 3, respectively. Anginal attacks were not induced in any patient on day 2 (BNP infusion). Fourteen minutes after BNP infusion was begun, plasma BNP levels increased from 23.7 +/- 6.7 pg/ml to peak levels of 2591 +/- 255 pg/ml (p < 0.01) and plasma ANP levels increased from 28.9 +/- 7.5 pg/ml to peak levels of 69.2 +/- 13.2 pg/ml. Five minutes after BNP infusion was finished, plasma levels of cyclic guanosine monophosphate (cGMP) increased from 20.3 +/- 7.4 pg/ml to peak levels of 63.5 +/- 13.7 pg/ml (p < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7985590 TI - Patients with high baseline exercise capacity benefit from cardiac rehabilitation and exercise training programs. AB - Despite the well-proven benefits of cardiac rehabilitation and exercise training, no data are available on the benefits of this therapy in patients with preserved baseline exercise capacity. Therefore we assessed data before and after phase II cardiac rehabilitation and exercise programs at two large teaching institutions to determine the benefits in 163 patients with high baseline exercise capacity (> or = 6 estimated [mean 8.8 +/- 2.4] metabolic equivalents [METs]) compared with 125 patients with low baseline functional capacity (< 6 estimated [mean 4.6 +/- 0.8] METs). After cardiac rehabilitation and exercise training, patients with high baseline exercise capacity had significant improvements in triglyceride ( 10%; p < 0.05), high-density lipoprotein cholesterol (+7%; p < 0.001), and low density lipoprotein cholesterol (-4%; p = 0.09) levels; low-density lipoprotein/high-density lipoprotein ratio (-10%; p < 0.01); body mass index ( 1.5%; (p < 0.001); percent body fat (-6%; p < 0.0001); and exercise capacity (+22%; p < 0.0001). Patients with high baseline exercise capacity had less relative improvement in exercise capacity (p < 0.0001) after cardiac rehabilitation but had greater relative improvement in low-density lipoprotein cholesterol level (p < 0.05) and low-density lipoprotein/high-density lipoprotein ratio (p < 0.05) than did patients with low baseline exercise capacity. These data demonstrate the benefits of cardiac rehabilitation and exercise training in patients with preserved exercise capacity and support routine referral of these patients to these programs after major cardiac events. PMID- 7985591 TI - Differential therapeutic responses of patients with isoproterenol-dependent and isoproterenol-independent vasodepressor syncope. AB - Orthostatic stress during tilt table testing (TTT) is used to examine patients who may have vasodepressor syncope. This response is thought to be mediated by activation of left ventricular mechanoreceptors. Isoproterenol, by increasing the rate of discharge of these mechanoreceptors, has been proposed to increase the sensitivity of TTT without decreasing its specificity. This mechanism is not, however, totally consistent with recent observations of vasodepressor responses after cardiac transplantation in patients with denervated hearts. These reports and data showing that not all sympathomimetic agents increase the sensitivity of TTT suggest that more than one mechanism may be responsible for a positive TTT result. Therefore we hypothesized that patients with positive TTT results tests not requiring isoproterenol (iso-independent) would have a different clinical and therapeutic response than patients who required isoproterenol (iso-dependent). One hundred sixty-one consecutive patients who underwent TTT for the evaluation of unexplained syncope were included in the study. TTT was performed without and during isoproterenol infusion. A positive TTT result was defined as syncope or presyncope with a sudden decrease in systolic blood pressure and reproduction of the patient's clinical symptoms. Patients with a positive TTT result underwent a second test after 1 to 2 weeks of therapy with an oral beta-blocking agent; if the result remained positive, TTT was performed again with other agents until a satisfactory therapeutic response was obtained. Sixty-six (41%) of 161 patients had a positive result; 18 (27%) were iso-independent, and 48 (73%) were iso dependent. There were no significant differences in age, gender, or presence of underlying heart disease between these two groups.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7985592 TI - Acute cocaine administration induces ventricular regional wall motion and ultrastructural abnormalities in an anesthetized rabbit model. AB - Whether acute doses of cocaine can induce left ventricular (LV) regional wall motion abnormalities in animals with otherwise normal coronary arteries is unknown. We studied rabbits receiving constant cocaine infusions (group I: 0.025 to 1.5 mg/kg/min, n = 10), multiple cocaine boluses (group II: 3-5 mg/kg each bolus, n = 10), or saline (group III; n = 8). In group I rabbits, short-axis LV area and diameter increased by 15% to 40% at 60 minutes compared to baseline and to controls (p < 0.01), but percentage of global area fractional shortening was unchanged. Eight rabbits in each of groups I and II, but no controls, developed LV regional wall motion abnormalities as detected by echocardiography: 15 (7 hypokinesis and 8 akinesis or dyskinesis) in the anteroseptal and 2 (hypokinesis) in the posterior LV wall. Among rabbits showing LV wall motion abnormalities, anteroseptal fractional shortening and % area reduction averaged > 20% less (p = 0.03 for area reduction) at 30 minutes versus controls. Only 50% of group I or II rabbits with LV anteroseptal wall motion abnormalities had intraventricular conduction disturbances. Radioactive microsphere flow studies (n = 6) 1 minute after a 4 mg/kg cocaine bolus revealed an equivalent decrease (10% to 20%, average) in septal and LV free wall perfusion (p value not significant). Electron microscopy revealed myocardial cell contraction band necrosis in 3 and sarcoplasmic reticular edema in 7 of 10 cocaine rabbits (unrelated to dose). We conclude that acute cocaine administration in rabbits frequently produces LV anteroseptal wall motion abnormalities even in the absence of differentially decreased perfusion or intraventricular conduction disturbances and produces ultrastructural abnormalities of the myocytes. These findings suggest a direct, nonuniform effect of cocaine on the LV myocardium. PMID- 7985593 TI - Three-dimensional visualization of velocity profiles in the human main pulmonary artery with magnetic resonance phase-velocity mapping. AB - Detailed data on blood velocity fields in the normal human main pulmonary artery are an essential platform for discriminating physiologic from pathologic pulmonary flow patterns. Over the years, many studies have revealed quite inconsistent data mainly because of lack of suitable measuring techniques. By using combined cardiac- and respiratory-triggered magnetic resonance phase velocity mapping, very consistent data were obtained in 12 volunteers. In all subjects the location of the highest axial velocities was shifted from the inferior-right toward the superior-left part of the vessel area during the right ventricular contraction, with rapidly decreasing velocities to the inferior right evolving into retrograde flow in the deceleration phase. The mean temporal velocity profile was consistently skewed with a low flow region also toward the inferior-right vessel wall. The magnetic resonance phase shift method used in this study provided remarkably consistent high-quality data about human pulmonary artery velocity fields. This is most likely because of the use of combined cardiac and respiratory triggering. PMID- 7985594 TI - Postoperative evaluation of pulmonary arteries in congenital heart surgery by magnetic resonance imaging: comparison with echocardiography. AB - Palliative and corrective operations for the treatment of cyanotic congenital heart disease frequently involve or potentially influence the size of the pulmonary arteries. Echocardiography and magnetic resonance imaging (MRI) are two noninvasive imaging techniques currently used to assess morphologic abnormalities of the pulmonary arteries. The purpose of this study was to evaluate the role of MRI in comparison with echocardiography for defining morphologic changes of the pulmonary arteries after congenital heart surgery. The MRI scans and echocardiograms of 33 patients with surgery involving or affecting the pulmonary arteries were compared. The pulmonary outflow tract, pulmonary confluence, right and left pulmonary arteries, and surgical shunts were separately evaluated. Cineangiography and surgical reports were used to confirm findings. MRI and echocardiography were equivalent for demonstrating abnormalities of the right ventricular outflow tract, main pulmonary artery, and a variety of pulmonary shunts. MRI was superior to echocardiography in demonstrating abnormalities of the right and left pulmonary arterial branches (p < 0.001). MRI is effective for monitoring pulmonary arterial status after surgery and is superior to echocardiography for the evaluation of the right and left pulmonary arteries. PMID- 7985595 TI - Influence of flosequinan on autonomic tone in congestive heart failure: implications for the mechanism of the positive chronotropic effect and survival influence of long-term vasodilator administration. AB - The vasodilator flosequinan has been shown to be effective in the management of symptoms of congestive heart failure but has been found to influence survival adversely when administered in selected doses. A moderate positive chronotropic response accompanies long-term administration of this agent, which may be associated with an activation of the neurohormonal axis that itself may contribute to the reported increase in mortality. This investigation used the technique of spectral analysis of heart rate variability to examine the autonomic response to long-term flosequinan administration in 39 patients enrolled in a double-blind placebo-controlled trial of this vasodilator to determine whether autonomic mechanisms account for the observed changes in heart rate. Although heart rate significantly increased in the flosequinan-treated patients, parasympathetic tone increased and sympathetic drive decreased compared with placebo, as reflected by high- and low-frequency heart rate variabilities, respectively. It is concluded that (1) autonomic inputs to the myocardium that would be expected to produce increases in heart rate do not result from long-term flosequinan administration; (2) accordingly, a direct positive chronotropic effect must account for the heart rate changes observed with this vasodilator; and (3) the increased mortality associated with the administration of this agent in the doses examined does not appear to result from reflex changes in autonomic tone and must result from other properties of this vasodilator. PMID- 7985596 TI - Effects of a novel inotropic agent (OPC-18790) on systolic and diastolic function in patients with severe heart failure. AB - A double-blind placebo-controlled study to determine the acute hemodynamic and cardiac mechanical effects of the quinolinone derivative OPC-18790 was performed in 12 patients with New York Heart Association class III or IV congestive heart failure. Simultaneous echocardiographic, Doppler, and invasive hemodynamic studies were performed before and after a 6-hour intravenous infusion of drug at 2.5, 5.0, or 10.0 micrograms/kg/min or of placebo. OPC-18790 (mean dose 5.9 +/- 3.5 mg) caused significant increases in left ventricular (LV) ejection fraction (15% +/- 4% vs 23% +/- 5%; p < 0.05) and cardiac index (1.7 +/- 0.4 vs 2.5 +/- 0.6 L/min/m2; p < 0.05) and a rightward and upward shift in the stress-shortening relation. LV end-diastolic volume and heart rate were unchanged. LV filling and posterior LV wall thinning rates from digitized M-mode echocardiographic studies (0.49 +/- 0.16 vs 0.75 +/- 0.21 cm/sec and 2.0 +/- 0.9 vs 3.0 +/- 1.4 cm/sec, respectively; both p < 0.05), transmitral deceleration time (67 +/- 24 vs 81 +/- 19 msec, p < 0.05), and atrial filling fraction (31.0% +/- 11.2% vs 38.9% +/- 13.9%, p < 0.05) increased with OPC-18790 infusion. Despite a significant decrease in pulmonary capillary wedge pressure (28 +/- 9 vs 18 +/- 10 mm Hg) there was no change in the velocity-time integral of early diastolic filling (53 +/- 12 vs 59 +/- 22 cm), suggesting improved LV relaxation. Hemodynamics and parameters of LV function were unchanged in the 3 patients receiving placebo.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7985597 TI - Attenuated endothelium-dependent peripheral vasodilation and clinical characteristics in patients with chronic heart failure. AB - Impairment of endothelium-dependent vasodilation has recently been reported in the peripheral vascular bed in patients with chronic heart failure. However, the clinical implications of this type of vascular dysfunction have yet to be elucidated. We have determined the degree of impairment of endothelium-dependent vasodilation as evaluated by acetylcholine-induced changes in forearm blood flow and compared this to various clinical parameters in 23 patients with chronic heart failure. Cumulative changes in forearm blood flow induced by acetylcholine (3.0 and 4.5 micrograms/min/dl tissue volume) were significantly lower in patients with chronic heart failure than in normal controls (10.1 +/- 8.0 ml/min/100 ml vs 20.4 +/- 11.7 ml/min/100 ml tissue volume; p < 0.01). In patients with heart failure, no significant relation was found between acetylcholine-induced changes in forearm blood flow and age, sex, duration of symptoms, duration of hospital stay, or resting hemodynamic parameters, although a significant positive correlation was observed with peak oxygen uptake (r = 0.53, p < 0.05) and ventilatory threshold (r = 0.42, p < 0.05). These observations suggest that the impairment of endothelium-dependent peripheral vasodilation may be one of the factors contributing to exercise intolerance in patients with chronic heart failure, probably resulting from its limiting effect on nutritive skeletal muscle blood flow during exercise. PMID- 7985598 TI - Use of skin conductance changes during mental stress testing as an index of autonomic arousal in cardiovascular research. AB - Mental stress testing is used to study the cardiovascular changes caused by psychologic stress. To examine the effects of cardiac drugs on mental stress induced changes, it is useful to attain a degree of arousal that can be replicated in serial studies. Skin conductance level, a cholinergically mediated index of arousal, was assessed for its stability in serial studies and under conditions of beta-blockade. In normal subjects, skin conductance increased in response to mental stress (p < 0.001) and was stable across three sessions. In patients with mild hypertension, skin conductance was elevated during mental stress during both placebo and nadolol therapy (p < 0.001). As expected, nadolol reduced baseline and stress-induced peak arterial pressure and heart rate but had no significant effect on skin conductance. Thus skin conductance level can serve as a stable and useful index of autonomic arousal in clinical trials, even in patients using beta-blocking medications. PMID- 7985599 TI - Long-term metabolic effects of antihypertensive drugs. AB - In short-term studies (4 to 6 months) we have reported that antihypertensive treatment with beta-adrenergic blockade and thiazide diuretics induced insulin resistance, hyperinsulinemia, and a deranged lipid profile; the ACE inhibitor captopril increased insulin sensitivity without affecting serum lipids. In the present study, 65 of the original 149 patients with essential hypertension included in the short-term studies were reexamined after treatment for 2 to 3 years. The hyperinsulinemic euglycemic clamp method showed that the significant decrease in insulin sensitivity (p < 0.01) induced by treatment with pindolol, propanolol, metoprolol, atenolol, or hydrochlorothiazide after 4 to 6 months persisted after 2 to 3 years of treatment. Furthermore, the increase in insulin sensitivity reported for captopril after 6 months (p < 0.05) was not significantly altered during long-term treatment. Also, the raised levels of very low-density lipoprotein triglycerides (p < 0.01) and reduced levels of high density lipoprotein cholesterol (p < 0.01) induced by most of the beta-adrenergic blockade without intrinsic sympathomimetic activity and hydrochlorothiazide persisted. Captopril, on the other hand, did not significantly affect the lipids during prolonged treatment. In conclusion, the magnitude of the metabolic effects induced by antihypertensive treatment during short-term studies was of the same order after long-term treatment over 2 to 3 years and were not significantly different from the results in the short-term studies. PMID- 7985600 TI - Effect of age on mortality in coronary artery bypass surgery in New York, 1991 1992. AB - The purpose of this study was to determine the effect of age on the in-hospital mortality of all 30,972 patients undergoing coronary artery bypass graft (CABG) surgery in New York in 1991 and 1992. Mortality rates were relatively low for patients 40-49, 50-59, and 60-64, 65-69, and 70-74 years old (1.10%, 1.65%, 2.17%, 2.76%, and 3.36%, respectively). However, CABG surgery mortality increased rapidly for patients 75 to 79 years old (5.28%) and patients > or = 80 years old (8.31%). To examine the independent effect of age on mortality after accounting for the effects of other significant risk factors, a multivariate statistical model was developed to identify the significant independent predictors of mortality. Age emerged as 1 of 24 significant predictors, with age > or = 75 demonstrating much higher mortality risk than lesser age. For example, the odds of an 80-year-old patient's dying in the hospital were 3.25 times the odds of a 50-year-old patient's dying in the hospital, assuming all other significant risk factors were identical. PMID- 7985601 TI - Failure of brief ischemic episodes to protect against myocardial dysfunction caused by ischemia and reperfusion in isolated rat hearts. AB - Brief periods of ischemia have been suggested to protect against myocardial injury caused by a subsequent episode of prolonged ischemia and reperfusion. However, the protective effects of brief ischemic periods against myocardial dysfunction after prolonged myocardial ischemia are controversial. To examine whether the protective effects of brief ischemic episodes relate to the extent of prior ischemic events, isolated rat hearts were subjected to either no preischemia (group A); one 5-minute episode of preischemia and 10 minutes of reperfusion (group B); or two 1-minute episodes of ischemia, each followed by 5 minutes of reperfusion (group C). All hearts were then subjected to 15 minutes of total ischemia and 10 minutes of reperfusion. In group A, after 10 min of reperfusion coronary perfusion pressure (CPP) was 31% +/- 10% (mean +/- SEM) higher than the control value, peak force of cardiac contraction (FCC) was 64% +/ 5% lower, and heart rate was 18% +/- 3% lower. In group B, CPP increased 26% +/- 6%, FCC fell 58% +/- 7%, and heart rate decreased 22% +/- 8% (group B vs group A, P value not significant) after ischemia and reperfusion. In group C, CPP increased 23% +/- 7%, FCC decreased 57% +/- 8%, and heart rate fell 8% +/- 4% on reperfusion (group C vs groups A and B, P value not significant). Creatine kinase (CK) was measured in the hearts from different groups and was found to be similar. Release of the adenosine triphosphate (ATP) metabolites hypoxanthine, inosine, and adenosine was also not different in the coronary effluents of the three groups of hearts.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7985602 TI - Natural history of vegetations during successful medical treatment of endocarditis. AB - Although initial morphologic features of vegetations have been related to the risk of early complications, there is little information about the natural history of the vegetations during medical treatment or the relation of morphologic changes in vegetation to late complications. To assess the evolution of valvular vegetations by echocardiography during treatment of infective endocarditis and to relate the morphologic changes in vegetation to late prognosis, serial echocardiograms of patients with successful medical treatment for native valve infective endocarditis were reviewed to assess the presence and morphologic features of valvular vegetations at the onset and at the end of therapy. The evolution of vegetation size, mobility, consistency, the extent of the disease, and the severity of valvular regurgitation were related to late complications such as embolism, valve replacement, or death occurring after the end of therapy. Forty-one vegetations were identified in 32 patients on initial echocardiograms. At the end of treatment, 29 vegetations were still present; 59% had no significant change in size and 52% appeared to be denser in consistency. Morphologic changes did not relate to late complications, but the presence of severe valvular regurgitations was associated with late valve replacement. The echocardiographic persistence of vegetations is common after successful medical treatment of infective endocarditis. In the absence of severe valvular dysfunction, however, persistent vegetations are not independently associated with late complications. PMID- 7985603 TI - Penetrating atherosclerotic aortic ulcers. AB - Penetrating atherosclerotic aortic ulceration is a unique disease with distinct management and prognostic implications. It is an important clinical entity that must be distinguished from classic aortic dissection and rapid expansion or contained rupture of a thoracic aortic aneurysm. Although symptoms of penetrating aortic ulceration may mimic dissection, the characteristic signs of dissection are absent. New imaging modalities have made it possible to establish the diagnosis of penetrating aortic ulceration with a high degree of accuracy and to tailor management according to the presence of complications. Physicians should be aware of the possibility of atherosclerotic aortic ulceration, particularly in elderly patients with systemic atherosclerosis and hypertension who have sudden onset of chest or back pain. PMID- 7985604 TI - Three-dimensional transesophageal echocardiography in the diagnosis of mitral valve prolapse. AB - Because the anulus of the mitral valve is nonplanar in systole, false-positive diagnosis of mitral valve prolapse may result from two-dimensional transthoracic echocardiography. Because of the superior image quality of TEE, we used the three dimensional TEE technique to evaluate the mitral valve in both normal subjects and patients with mitral valve prolapse and with ruptured chordae tendineae. After a conventional TEE examination, sequential images of longitudinal views were obtained by probe rotation. The images at 5-degree intervals were stored in machine cine memory loop; the special temporal images were selected with ECG gating and videorecorded. During the examination, 6 to 8 images of the left heart were recorded for later off-line, three-dimensional reconstruction. A total of 42 subjects were studied: 32 normal, 9 with mitral valve prolapse, and 1 with ruptured chordae tendineae. In normal subjects, three-dimensional TEE showed nonplanarity of the entire mitral valve, which assumes a saddle shape. In mitral valve prolapse, either the anterior or posterior leaflet protruded into the left atrium like a spoon; when both leaflets are involved, they prolapse like two spoons. The anterior and posterior leaflets coapted poorly, and there was a seam between them. In ruptured chordae tendineae the tip of the mitral leaflet protruded during systole into the left atrium far from the coaptation point and was perpendicular to the body of the mitral valve and parallel to the anterior and posterior walls of the left atrium.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7985605 TI - Pediatric biplane transesophageal echocardiography: preliminary experience. AB - Recent development of prototype pediatric biplane transducers has extended the use of biplane TEE imaging to the neonate. One such TEE probe with 64 imaging elements in each pallet was used perioperatively in 46 infants and children (weight 2.9 to 32 kg) undergoing surgery for complex congenital heart disease. The success rate for passing the transducer, complications of the procedure, and the number of cases in which the vertical plane provided information that was not available from the horizontal plane were determined. Probe insertion was successful in all patients. Imaging was discontinued in one neonate because of possible airway compression by the probe. Image quality was excellent in the other 45 patients. The vertical plane added information over that obtained from the horizontal plane in 58 (44%) of the 132 anomalies identified. The addition of the vertical plane was especially useful in imaging abnormalities of the ventricular outflow tracts. PMID- 7985606 TI - Myocardial infarction, aortic dissection, and thrombolytic therapy. PMID- 7985607 TI - Acute myocardial infarction resulting from amphetamine abuse: a spasm-thrombus interplay? PMID- 7985608 TI - Urokinase resolution of impending paradoxic embolus in transit: evaluation by multiplane transesophageal echocardiography. PMID- 7985609 TI - Syncope as the initial symptom of silent coronary vasospasm. PMID- 7985610 TI - Primary antiphospholipid syndrome and mitral valve thrombosis. PMID- 7985611 TI - Lactobacillus isolated pulmonic valve endocarditis with ventricular septal defect detected by transesophageal echocardiography. PMID- 7985612 TI - Development of ventriculogastric fistula after left ventricular aneurysmectomy. PMID- 7985613 TI - Transthoracic and transesophageal echocardiographic diagnosis of severe subaortic obstruction produced by an abscess cavity. PMID- 7985614 TI - Theophylline reverses high-grade atrioventricular block resulting from cardiac transplant rejection. PMID- 7985615 TI - Revisiting carotid sinus denervation in carotid sinus hypersensitivity. PMID- 7985616 TI - Alteration of phasic flow-velocity pattern during occlusive coronary artery spasm. PMID- 7985617 TI - Becker-type muscular dystrophy associated with hypertrophic cardiomyopathy. PMID- 7985618 TI - Dental disease and coronary artery disease. PMID- 7985619 TI - Limb-compartmental syndrome with thrombolysis. PMID- 7985620 TI - Calcium and osteoporosis. AB - Skeletal size and mass are genetically programmed. Optimum skeletal size can be attained if the nutrient supply, ie, calcium, is ample, but the age-dependent decrease in skeletal mass that begins in the third decade cannot be arrested by adequate calcium intake alone. The decrease in skeletal mass is primarily caused by the age-dependent decrease in gonadal hormones. The dramatic drop in hormones in menopause is associated with a sharp decrease in trabecular bone and a slower decrease in cortical bone. In men this decrease is gradual. Replacement therapy with gonadal hormones can markedly slow this decrease in bone mass, provided calcium intake is adequate. Soluble forms of calcium are preferred to ensure adequate calcium absorption. Vitamin D supplementation beyond the recommended dietary allowance does not appear beneficial in osteoporosis, but may be so in cases of senile hyperparathyroidism. Calculations based on bone calcium turnover indicate that the recommended dietary allowance for calcium is adequate for boys and men, but is insufficient for adolescent girls. Calcium intake by women is probably too low to slow bone calcium turnover to its programmed minimum. Adequate calcium intake in childhood and adolescence is essential to attain the optimal bone mass and size. PMID- 7985621 TI - Uncritical use of bone mineral density in absorptiometry may lead to size-related artifacts in the identification of bone mineral determinants. AB - Epidemiological studies of bone mineral determinants rely heavily on measurements made with absorptiometric techniques such as single-photon absorptiometry and dual-energy x-ray absorptiometry. In general, absorptiometric data are expressed as areal densities (bone mineral density, BMD), obtained by dividing bone mineral content (BMC) by bone area or width (BA, BW). This size correction assumes that BMC and BA (BW) are directly proportional to one another, such that a 1% change in BA (BW) is matched by a 1% change in BMC. This is rarely the case, and the exact relationship depends on the population group, skeletal site, body size, instrumentation, and scanning conditions. Size adjustment determined by using predefined indexes, such as BMD and body mass index (BMI, wt/ht2), may fail to correct BMC fully for bone and body size, and may lead to spurious associations with other size-related variables such as calcium intake, energy expenditure, and grip strength. A general approach to size adjustment is described, in which BA (BW), weight, and height are incorporated in all regression models of BMC. Although BMD plays a valuable role in fracture-risk assessment and clinical management, we advocate that its use in epidemiological research be discontinued. PMID- 7985622 TI - Total and regional body-composition changes in early postmenopausal women: age related or menopause-related? AB - Total and regional body composition were measured in 373 early postmenopausal women aged 49-60 y by dual-energy x-ray absorptiometry to evaluate whether the changes in body composition in the early postmenopausal years are related to menopause itself or merely to age. Both fat mass and fat distribution correlated with age (r = 0.12-0.21, P < 0.05-P < 0.001), but not with years since menopause (YSM). Lean tissue mass, on the other hand, decreased with YSM (r = -0.17, P < 0.001) but was not related significantly to age. Total body bone mineral density decreased with both YSM (r = -0.30, P < 0.001) and age (r = -0.21, P < 0.001). Our study suggests that postmenopausal changes in body fat and fat distribution are more dependent on age than on menopause, but we cannot exclude a separate effect of the menopause. Changes in fat-free mass, including a postmenopausal decline in both soft lean tissue mass and bone mass, are, however, mainly menopause-related PMID- 7985623 TI - Reproducible measurement of postprandial energy expenditure in young healthy males. AB - The reproducibility of measurements of postprandial energy expenditure (PEE) was determined by assessing, for 345 min, the diet-induced thermogenesis (DIT) of a 4055-kJ mixed meal in 10 lean young men on four occasions. The DIT was determined by using either a 20-min premeal baseline metabolic rate (method 1) or a single resting metabolic rate (RMR) measured on a separate day (method 2). The DIT, in kilojoules, for a given subject calculated by method 1 varied significantly between occasions, CV 15.4% (P < 0.05). The D peak (PEE peak minus baseline) did not vary significantly between the four trials (CV 13%). The results obtained by using method 2 were much more reproducible for both the DIT (CV 4.2%) and the D peak (CV 4.8%). Thus, the reproducibility of the PEE measurement is enhanced by using an RMR measured on a separate day and by using the postprandial peak value instead of the DIT. PMID- 7985624 TI - Underestimation of energy intake by 3-d records compared with energy intake to maintain body weight in 269 nonobese adults. AB - We assessed how accurately participants in dietary trials reported their free living energy intake. We compared self-reported energy intake, calculated from 3 d food records, with actual intakes needed to maintain body weight during controlled trials lasting 6-9 wk. In 269 free-living healthy male (n = 119) and female (n = 150) adults with mean body weights close to ideal values (mean +/- SD body mass index in kg/m2, 22.1 +/- 2.4), energy intake reported in food records was 1.2 +/- 1.6 MJ/d (277 +/- 378 kcal/d) lower than actual energy requirements during the experiments. The relative bias was significantly smaller (P = 0.01) for men (-8.0 +/- 13.4%) than for women (-12.2 +/- 13.7%). Body mass index, daily energy intake, and age were not significantly related to the extent of underestimation. We conclude that food records systematically underestimate energy needs in young, nonobese well-educated adults. PMID- 7985625 TI - Recovery of initial body weight and composition after long-term massive overfeeding in men. AB - To verify the existence of a set point for body mass, the spontaneous evolution of body weight and composition after massive overfeeding was observed in nine lean young Cameroonian (Massa) men participating in a 4-6 mo traditional fattening session (Guru). Anthropometry (skinfold thicknesses) was used to estimate body composition. Peak weight and fat gains were found to be 19 +/- 3.2 (mean +/- SD) kg and 11.8 +/- 2.5 kg, respectively. Two and one-half years after cessation of fattening and a return to daily life and food habits, there was a spontaneous return to initial body weight and body composition of the overfed subjects. Because the subjects were not under social or other stimuli to lose weight, this finding argues in favor of the existence of a biological control of energy balance at a "preferred" level in nonobese individuals. PMID- 7985626 TI - Eating behavior in bulimia nervosa: multiple meal analyses. AB - Ten bulimic individuals were admitted to an inpatient unit and for 7 consecutive days eating behavior was observed and recorded. Age, sex, and weight-matched control subjects (n = 10) were admitted to the same unit for 4 d. All food and fluid intake, frequency of binge eating and purging, and ratings of appetite and mood before and after eating were recorded every 24 h. Bulimic patients demonstrated chaotic eating patterns that varied within as well as between individuals. Total daily energy intake was significantly higher for bulimic patients (41982 +/- 113 kJ; 10,034 +/- 2701 kcal) than for control subjects (8050 +/- 0427 kJ; 1924 +/- 102 kcal). On average, patients binged 1.6 times, purged three times, and ate one snack or meal without purging daily. Macronutrient analyses of intake revealed significantly less energy from protein and more energy from fat in bulimic patients compared with control subjects. Some improvement of mood was noted after binges, the magnitude of which was greatest after purging. PMID- 7985627 TI - Influence of degree of obesity on loss of fat-free mass during very-low-energy diets. AB - This study examined the influence of initial degree of obesity on loss of fat free mass (FFM). One hundred twelve obese females participated in a series of very-low-energy diet (VLED) clinical trials. Obesity groups were determined by three common methods: percent body fat, body mass index, and weight. Within each group, subjects were classified into low-, intermediate-, and high-obesity groups. As expected, the high-obesity group lost comparable amounts or more weight and more fat weight than the low- and intermediate-obesity classifications for each group. The high-obesity group lost approximately 2% more FFM (P < 0.05) compared with the low and intermediate group when subjects were grouped by body mass index and weight and showed no differences between classifications when subjects were grouped by percent body fat. No differences were found between classifications for ratios of FFM to weight loss regardless of how subjects were grouped. Thus, the degree of obesity does not seem to affect loss of FFM. PMID- 7985628 TI - Effects of feeding on the small intestinal mucosa of beagle pups during the first 5 d of life. AB - To further define the effects of feeding on small intestinal ontogeny, naturally suckled and formula-fed beagle pups were studied over the first 120 h of life. In suckled animals, proximal jejunal and midintestinal mucosal weight and protein and DNA contents increased > 75% by 24 h (P < 0.005), with no further increases at 120 h. In formula-fed pups, no mucosal mass changes were found between 0 and 72 h of life. At 120 h, proximal jejunal mucosal weight and protein and DNA contents were significantly greater than in newborns (P < 0.005) and were similar to values for suckled animals at the same time. No significant mid-intestinal or terminal ileal growth was noted in formula-fed pups at any time. Specific and total activities of proximal jejunal brush border lactase, sucrase, and alkaline phosphatase were significantly greater in suckled vs formula-fed animals at 120 h. In a parallel study to assess postnatal effects of mature milk vs colostrum, significant mucosal growth at 24 h of life was demonstrated in pups suckled by surrogate dams who had whelped 21 d previously. These data indicate that both natural suckling (colostrum or milk) and formula feeding support enteric mucosal growth in newborn dogs; however, the two feeding regimens are characterized by unique ontogenic patterns of intestinal mucosal growth and function. PMID- 7985629 TI - Vegetarian vs nonvegetarian diets, dietary restraint, and subclinical ovulatory disturbances: prospective 6-mo study. AB - Ovulatory function was prospectively assessed over 6 mo in 23 vegetarians and 22 nonvegetarians with clinically normal menstrual cycles. Subjects were 20-40 y of age, of stable weight (body mass index, in kg/m2, of 18-25), on current diets for > or = 2 y, and not using oral contraceptives. Quantitative analysis of basal body temperature records classified cycles as normally ovulatory, short luteal phase (< 10 d), or anovulatory. Subjects completed the Three-Factor Eating Questionnaire (subjects completed the Three-Factor Eating Questionnaire (subscales for restraint, hunger, and disinhibition) and kept three 3-d food records. Vegetarians had lower BMIs (21.1 +/- 2.3 vs 22.7 +/- 1.9, P < 0.05), percentage body fat (24.0 +/- 5.5% vs 27.4 +/- 5.1%, P < 0.05), and restraint scores (6.4 +/- 4.4 vs 9.5 +/- 3.7, P < 0.05). Mean cycle lengths were similar, but vegetarians had longer luteal phase lengths (11.2 +/- 2.6 vs 9.1 +/- 3.8 d, P < 0.05). Cycle types also differed (chi 2 = 9.64, P < 0.01): vegetarians had fewer anovulatory cycles (4.6% vs 15.1% of cycles). Compared with those with restraint scores below the median, highly restrained women had fewer ovulatory cycles (3.6 +/- 2.3 vs 5.0 +/- 1.4, P < 0.05) and shorter mean luteal phase lengths (7.4 +/- 4.1 vs 10.7 +/- 3.1 d, P < 0.05). We conclude that ovulatory disturbances and restrained eating are less common among vegetarians, and that restraint influences ovulatory function. PMID- 7985630 TI - Effect of the menstrual cycle on energy and nutrient intake. AB - Midfollicular and midluteal dietary intakes of 18 women were evaluated between four and six ovulatory menstrual cycles. Phase lengths were established by basal body temperatures and urinary luteinizing hormone excretion. Midfollicular and midluteal diet records were collected 6-8 d after menstrual onset and 6-8 d after ovulation, respectively. Significant increases in energy [0.66 MJ (159 kcal), P = 0.003], protein (6.1 g, P = 0.02), carbohydrate (15.3 g, P = 0.04), and fat (8.6 g, P = 0.002) intakes were observed in midluteal phase when compared with midfollicular phase. Intakes of vitamin D, riboflavin, potassium, phosphorus, and magnesium also were significantly higher during midluteal phase (P < 0.05). These results support the regulation of food intake by menstrual cycle hormones and suggest that it is essential to consider phase of menstrual cycle in studies of nutrient intake performed in premenopausal women. PMID- 7985631 TI - Postnatal changes in plasma chain-breaking antioxidants in healthy preterm infants fed formula and/or human milk. AB - Concentrations of chain-breaking antioxidants were studied in the first 6 postnatal weeks in 29 healthy preterm infants (gestational age 30-35 wk). Vitamin C, uric acid, and sulfhydryl groups declined, whereas vitamin E rose and bilirubin followed its typical biphasic postnatal course. The influence of these changes on the plasma peroxyl radical trapping capacity was assessed in vitro (TRAP assay). The trapping capacity decreased postnatally and this appeared to be related to the coincident fall in uric acid concentrations. Results did not differ between babies fed with only preterm formula (n = 12) and those fed predominantly with human milk (n = 6), except for higher bilirubin and TRAP values in the breast-fed infants. There are major postnatal changes in the concentrations of the plasma chain-breaking antioxidants and this may influence the susceptibility of the preterm baby to oxygen toxicity. PMID- 7985632 TI - Infant vitamin B-6 status changes with age and with formula feeding. AB - To study the effect of type of feeding on infant vitamin B-6 status, we determined erythrocyte pyridoxal 5'-phosphate concentration (EPLP) and erythrocyte aspartate aminotransferase basal activity (EASTo) and its activation coefficient (alpha EAST) in 109 infants at 2, 4, 6, 9, and 12 mo of age. Thirty six infants were exclusively breast-fed for 9 mo. Forty-six infants were exclusively breast-fed for 6 mo, and then given solid foods in addition. Twenty seven infants were weaned by 2-3 mo to an adapted cow milk-based formula (15 g protein/L and 0.6 mg pyridoxine/L) and given solid foods from 3 to 4 mo. Infant vitamin B-6 status was age-dependent; it was highest at 4 mo and thereafter gradually approached adult values. The larger the intake of formula, the higher the vitamin B-6 status. In formula-fed infants at ages 2-6 mo, 71-96% of the EPLP values and 57-70% of the EASTo values were above the 95th percentile, and 35-53% of the alpha EAST values were below the 5th percentile for these values in breast fed infants. These findings raise the question of whether the vitamin B-6 content of formulas, especially in relation to protein content, should be reduced. PMID- 7985633 TI - Effects of a diet restricted in saturated fatty acids and cholesterol on the composition of apolipoprotein A-I--containing lipoprotein particles in the fasting and fed states. AB - To test the hypothesis that diet may exert differential effects on apolipoprotein (apo) A-I--containing high-density-lipoprotein (HDL) particles with (w) and without (w/o) apo A-II [Lp(A-I w A-II) and Lp(A-I w/o A-II)], the effects of a diet low in saturated fatty acids and cholesterol [National Cholesterol Education Panel (NCEP) Step 2 diet] on these lipoproteins were determined in eight normolipidemic subjects, aged 53-74 y, in both the fasting and nonfasting states. Compared with a diet high in saturated fatty acid and cholesterol, consumption of an NCEP diet (6 mo) lowered fasting plasma, low-density-lipoprotein, and HDL cholesterol, and nonfasting plasma cholesterol, triglyceride, and HDL cholesterol (P < 0.05- < 0.005). Phospholipid in fasting and nonfasting Lp(A-I w A-II) and Lp(A-I w/o A-II) was lower during the NCEP diet (P < 0.05-0.001), but reductions in apo A-I or A-II were observed only in Lp(A-I w A-II). In contrast, differences in particle-size profiles were detected in Lp(A-I w/o A-II) but not in Lp(A-I w A II). These observations provide further evidence that Lp(A-I w A-II) and Lp(A-I w/o A-II) are distinct metabolic entities. PMID- 7985634 TI - Effect on blood lipids, coagulation, and fibrinolysis of a fat high in myristic acid and a fat high in palmitic acid. AB - The hypothesis that myristic acid (C14:0) has a stronger cholesterol-increasing potential than does palmitic acid is based on very few experimental observations. A randomized, strictly controlled dietary study was therefore designed to investigate the effect of a synthetic fat that was high in myristic acid, and palm oil, which is high in palmitic acid, on lipoproteins and hemostatic variables. Twelve men were served two diets (40% of energy as fat) with 41% of fat as myristic (diet M) or palmitic acid (diet P) for 3 wk with 1 mo between the two dietary schedules. Plasma HDL cholesterol was 8% higher with diet M than with diet P: 1.10 +/- 0.06 (mean +/- SEM) vs 1.01 +/- 0.05 mmol/L (P < 0.006). Diet M raised factor VII coagulant (F VIIc) activity to 98% (77-117%) vs 96% (71-109%) (medians and ranges) after diet P (P = 0.02). Total and LDL-cholesterol concentrations did not differ between the diets. In conclusion, the myristic acid test fat was not more cholesterolemic than was palm oil, but it did induce a minor rise in F VIIc activity. PMID- 7985635 TI - Tolerance and absorption of lactose from milk and yogurt during short-bowel syndrome in humans. AB - This study aimed to compare the absorption and tolerance of 20-g lactose loads as milk and yogurt in 17 patients with short-bowel syndrome with either a terminal jejunostomy (group A, n = 6) or a jejunocolic anastomosis (group B, n = 11). Records and measurements during the 8 h after the meals included fecal weight, symptoms, lactose and hexose flow rates in stomal effluents (group A), and breath hydrogen excretion (group B). In group A lactose was better absorbed in the form of yogurt than in the form of milk (mean +/- SE: 76 +/- 6% vs 50 +/- 9%, P < 0.05), whereas no significant difference could be detected by using the breath hydrogen test in group B. The excellent tolerance to 20 g lactose from milk and yogurt suggests that lactose should not be excluded from the diet of these subjects. PMID- 7985636 TI - Premature infants require additional folate and vitamin B-12 to reduce the severity of the anemia of prematurity. AB - One hundred eighty-four premature infants, < 1800 g at birth and < 36 wk gestation, were entered into a study investigating the role of additional folate and vitamin B-12 supplementation of the anemia of prematurity. All patients initially received vitamin E and iron in accordance with accepted standards. Patients were randomly assigned to four groups to receive orally 0.1 mg folate/d for 4 mo, 100 micrograms vitamin B-12 intramuscularly monthly for 4 mo, both supplements, or neither. All other activities including parenteral nutrition were carried out according to established practices, irrespective of study group. By 10-12 wk, infants treated with vitamin B-12 alone or combined with folate had higher hemoglobin values than the untreated (P < 0.0005) or solely folate-treated (P < 0.01) groups. These findings held true irrespective of wide variations in treatment and feeding practices. The only uncontrolled hematologic nutritional factor, selenium, showed a similar pattern of decline for 10-12 wk in all study patients, whether or not they received additional vitamin supplements. PMID- 7985637 TI - Changes in serum carotenoids in subjects with colorectal adenomas after 24 mo of beta-carotene supplementation. Australian Polyp Prevention Project Investigators. AB - The effect of beta-carotene supplementation on major serum carotenoid fractions (lutein/zeaxanthin, beta-cryptoxanthin, lycopene, alpha-carotene, and beta carotene) was investigated in 224 people with colorectal adenomas (139 men, 85 women) recruited for the Australian Polyp Prevention Project (APPP). Each subject was randomly assigned to take either 20 mg beta-carotene/d or placebo over 24 mo. Besides the expected increase in serum concentration of beta-carotene (1073% in men, 839% in women), lycopene (176% in men) and alpha-carotene (211% in men and 166% in women) concentrations were also increased after body mass index, baseline concentration, change in respective carotenoid intake, and other confounding factors were adjusted for. The increase in serum concentrations of these carotenoids after beta-carotene supplementation suggests that beta-carotene may interact biologically with other carotenoids and such interaction would need to be taken into consideration when the protective effect of beta-carotene supplementation for cancer or other diseases is examined. PMID- 7985638 TI - Calcium requirement--a reappraisal of the methods used in its determination and their application to patients with osteoporosis. AB - The accepted practice of calculating the dietary calcium requirement from the relationship between calcium balance and intake was recently criticized on mathematical grounds. To try to determine the appropriate calcium intake in patients with osteoporosis, I examined the relationships between calcium intake, output, and balance in a group of such patients. Calcium-balance studies were performed on 25 patients with untreated osteoporosis: intake (x +/- SEM) was 30.34 +/- 3.02 mmol/d, output was 30.59 +/- 2.69 mmol/d, and calcium balance was 0.25 +/- 0.64 mmol/d. There was a significant correlation between intake and both output and balance (r = 0.98, P < 0.001 and r = 0.61, P < 0.01, respectively). Intake and output became equal at 31.7 (95% CI 27.9, 35.5) mmol/d. This value is the same as that obtained when the conventional method of calculation is used. Furthermore, if random values for calcium output are assigned to the observed values of intake it can be demonstrated that the same values will always be obtained by both methods The only difference is that the calculation based on balance and intake results in a narrower confidence interval. PMID- 7985639 TI - Sex affects manganese absorption and retention by humans from a diet adequate in manganese. AB - Men (n = 20) and women (n = 20) consuming a diet adequate in manganese were fed 0.037 mBq 54Mn in a test meal. Subjects were counted in a whole-body counter for 70 d to determine whole-body retention of 54Mn. Data from days 10 to 20 and from days 19 to 70 were analyzed by linear regression to calculate absorption and biological half-life. Men absorbed significantly less 54Mn than women, but the 54Mn absorbed had a longer half-life in men. Estimates of absorption were higher, and estimates of half-life were lower, when data from days 10 to 20 were used compared with days 19 to 70. There was a significant association between manganese absorption and plasma ferritin concentrations and between manganese absorption and biological half-life. We conclude that men and women differ in manganese metabolism and that such differences may be related to iron status. We also conclude that regression estimates of absorption determined by using whole body retention curves depend on the portion of the data used. PMID- 7985640 TI - Energy balance and expenditure while consuming guar gum at various fat intakes and ambient temperatures. AB - We devised a new model to evaluate whether dietary composition affects whole-body energy metabolism in rats. Dietary guar gum, but not corn starch, elevates both fecal energy excretion and energy expenditure. Neither ambient temperature (21 vs 28 degrees C) nor fat content of the basal diet (15% vs 33% metabolizable energy) has a marked effect on guar gum's thermogenic stimulus. Starch and guar gum each contribute 17.5 kJ/g to gross energy intake. This energy is fully available from the starch but guar gum contributes only 9-13 kJ/g to digestible energy intake on the low-fat diet (15% of energy), only 6 kJ/g to digestible energy on the higher fat diet (33% of energy) (because of a fat-gum interaction), decreases urinary energy loss by 1.4-2.7 kJ/g gum, and elevates energy expenditure by 11.6-14.8 kJ/g. The thermogenic effect of the guar gum is highly reproducible. Several potential mechanisms to explain such elevated energy expenditure are considered. The model used to quantify the thermogenic stimulus is highly sensitive and could be applied to the trial of potentially thermogenic drugs as well as dietary ingredients. PMID- 7985641 TI - Oral calcium suppresses biochemical markers of bone resorption in normal men. AB - Calcium supplementation decreases bone resorption and retards bone loss in women. There is little information about the effects of calcium supplementation in men. The effects of a 1-g oral calcium load at 0900 on bone-related biochemical variables were evaluated in 13 normal men (aged 51-70 y). Calcium administration was associated with increases in plasma ionized calcium (P < 0.001) and urinary calcium (P < 0.001), and a decrease in plasma parathyroid hormone (P < 0.001). There was a nonsignificant trend (r = -0.47, P = 0.11) for the decrease in plasma parathyroid hormone to be related to radiocalcium absorption. After the calcium load there were decreases in the urinary hydroxyproline-creatinine ratio from 11 +/- 1.1 to 7.9 +/- 0.6 (P < 0.01), the urinary deoxypyridinoline-creatinine ratio from 14.0 +/- 1.8 to 10.1 +/- 0.9 (P < 0.05), and the urinary pyridinoline creatinine ratio from 52 +/- 5 to 40 +/- 3 (P < 0.01) between baseline and 6 h. There was no change in plasma osteocalcin. These observations indicate that a 1-g calcium load suppresses biochemical markers of bone resorption for > or = 6 h in normal men and support the concept that calcium supplementation may be useful in the prevention of bone loss in men. PMID- 7985642 TI - Effect of a low beta-carotene diet on the immune functions of adult women. AB - We examined the effect of beta-carotene depletion and repletion on the immune status of nine healthy women who lived in the metabolic suite for 100 d. For the first 4 d all women were fed a basal diet supplemented with 1.5 mg beta carotene/d (baseline). During the next 68 d, the basal diet without beta-carotene supplementation was fed to all subjects (depletion), and during the last 28 d the diet of each women was supplemented with 15.0 mg beta-carotene/d (repletion). Neither beta-carotene depletion nor repletion significantly (P < or = 0.05) altered proliferation of peripheral blood mononuclear cells cultured with phytohemagglutinin or concanavalin A, in vitro production of soluble interleukin 2 receptor, or the concentration of circulating lymphocytes and their subsets. Thus, in healthy adults consuming adequate vitamin A, beta-carotene depletion had no adverse effect on the indexes tested, nor was there any beneficial effect of modest beta-carotene supplementation. PMID- 7985643 TI - Role of essential fatty acids: dangers in the US Department of Agriculture dietary recommendations ("pyramid") and in low-fat diets. PMID- 7985644 TI - Which study group is which? PMID- 7985645 TI - Glucose diffusion as a rate-limiting step in glucose absorption. PMID- 7985646 TI - Is leucine produced by the colonic microflora? PMID- 7985647 TI - Cigarette smoking: an independent risk factor for impotence? AB - The authors sought to determine whether current cigarette smoking was associated with impotence among middle-aged men. This is a secondary analysis of a cross sectional survey of 4,462 US Army Vietnam-era veterans aged 31-49 years who took part in the Vietnam Experience Study in 1985-1986. The main outcome measurement was the odds ratio for reported impotence, which was calculated by comparing current smokers with nonsmokers while controlling for multiple confounders. The study sample consisted of 1,162 never smokers, 1,292 former smokers, and 2,008 current smokers. The prevalence of impotence was 2.2% among never smokers, 2.0% among former smokers, and 3.7% among current smokers (p = 0.005). The unadjusted odds ratio (OR) of the association between smoking and reported impotence was 1.8 (95% confidence interval (CI) 1.2-2.6). The association held even after adjustments were made for confounders, including vascular disease, psychiatric disease, hormonal factors, substance abuse, marital status, race, and age (OR = 1.5, 95% CI 1.0-2.2). Neither years smoked nor cigarettes smoked daily were significant predictors of impotence in current smokers. The authors concluded that, among the men in this study, a higher percentage of cigarette smokers reported impotence than did nonsmokers. This observation could not be totally explained by comorbidity factors related to smoking. PMID- 7985648 TI - Cohort study of silicon carbide production workers. AB - Silicon carbide is produced by a chemical reaction at high temperature between free crystalline silica and petroleum coke. The process generates airborne fibers and fibrogenic dusts such as alpha-quartz and cristobalite, which are also potentially carcinogenic. The authors report that this is the first cohort study in this industry. The study was carried out among 585 Quebec silicon carbide production workers who had worked at any time from 1950 to 1980. Follow-up was to December 31, 1989, and 167 deaths were observed. The standardized mortality ratio (SMR) for all causes of death was 1.05 (95% confidence interval (CI) 0.90-1.23); for nonmalignant respiratory diseases it was 2.03 (95% CI 1.21-3.22); and for lung cancer it was 1.69 (95% CI 1.09-2.52). Controlling for smoking status using a Cox regression analysis, the risk for nonmalignant respiratory diseases and for lung cancer increased with exposure to total dust; in the highest exposure category, rate ratios (RR) were 4.08 (95% CI 1.11-14.96) for nonmalignant respiratory diseases and 1.67 (95% CI 0.57-4.83) for lung cancer. Results were in the expected direction, but the power of the study was low, because of small sample size and use of cumulative total dust as the exposure variable, which may be a poor indicator of lung irritants and other potential carcinogens in this industry, notably silicon carbide ceramic fibers. PMID- 7985649 TI - Test of the National Death Index and Equifax Nationwide Death Search. AB - The authors compared the ability of the National Death Index and the Equifax Nationwide Death Search to ascertain deaths of participants in the Nurses' Health Study. Each service was sent information on 197 participants aged 60-68 years in 1989 whose deaths were reported by kin or postal authorities and 1,997 participants of the same age who were known to be alive. Neither service was aware of the authors' information regarding participants' vital status. The sensitivity of the National Death Index was 98 percent and that of Equifax was 79 percent. Sensitivity was similar for women aged 65-68 years; however, for women aged 61-64 years, the sensitivity of the National Death Index was 97.7 percent compared with 60.2 percent for Equifax. The specificity of both services was approximately 100 percent. The contrast between the sources of these databases and the matching algorithms they employ has implications for researchers and for those planning health data systems. PMID- 7985650 TI - Objective system for interviewer performance evaluation for use in epidemiologic studies. AB - In this paper, the authors present an objective system to evaluate interviewer performance for use in epidemiologic studies. With this quality control system, all study interviews are audio-taped, and a random sample of interviews are coded according to interviewer behaviors, such as whether the interviewer asked the questions exactly as written and used the probes appropriately. With the use of data obtained from a large case-control study of colon cancer, the authors observed that 94.2% of all questions were asked in the same manner by all interviewers and that 89.5% of all probing behaviors were appropriate. They show that questions that required additional interviewer behaviors were more likely to result in variation in response that can be attributed to the interviewer. These findings have implications for study design and interpretation of study results. From simulations, the authors have estimated the impact of uncorrected interviewer variability on study power and ability to detect disease associations. Uncorrected interviewer variability could decrease study power from 84% to 56%. From simulations, the authors observed that odds ratios could be biased downward from 1.8 to 1.3. These findings illustrate the importance of using a continuous quality control program in epidemiologic research. PMID- 7985651 TI - Minimum sample size estimation to detect gene-environment interaction in case control designs. AB - As genetic markers become more available, case-control studies will be increasingly important in defining the role of genetic factors in disease causality. The authors estimate the minimum sample size needed to assure adequate statistical power to detect gene-environment interaction. One assumption is made: the prevalence of exposure is independent of marker genotypes among controls. Given the assumption, six parameters (three odds ratios, the prevalence of exposure, the proportion of those with the susceptible genotype, and the ratio of controls to cases) dictate the expected cell sizes in a 2 x 2 x 2 table contrasting genetic susceptibility, exposure, and disease. The three odds ratios reflect the association between disease and 1) exposure among non-susceptibles; 2) susceptible genotypes among nonexposed individuals; and 3) the gene environment interaction itself, respectively. Given these parameters, the number of cases and controls needed to assure any particular Type I and Type II error rates can be estimated. Results presented here demonstrate that case-control designs can be used to detect gene-environment interaction when there is both a common exposure and a highly polymorphic marker of susceptibility. PMID- 7985652 TI - Intraclass correlation among common measures of adolescent smoking: estimates, correlates, and applications in smoking prevention studies. AB - Most adolescent smoking prevention studies employ designs in which classrooms, schools, school districts, or sometimes whole communities are assigned to treatment conditions while observations are made on individual students. The critical design feature in such community trials is the nesting of intact social groups within treatment conditions. This combination requires that the treatment effect be assessed against the between-group variance; unfortunately, that variance is usually larger than for randomly constituted groups and its precision is usually less than that for the within-group variance. These factors often combine to reduce power so that it is almost impossible to detect important treatment effects in an otherwise well designed and properly executed study. To address these problems, investigators need good estimates of the intraclass correlation for the variables of interest, which together with the number of observations per unit determine the magnitude of the extra variation in the nested design. The purpose of this paper is to describe the methods and results from a study designed to generate estimates of intraclass correlation for common outcomes in adolescent smoking prevention studies and to discuss the use of these estimates in the planning of new studies. PMID- 7985653 TI - Re: "Risk attribution and tobacco-related deaths". PMID- 7985654 TI - Re: "Risk attribution and tobacco-related deaths". PMID- 7985655 TI - Re: "Should we consider a subject's knowledge of the etiologic hypothesis in the analysis of case-control studies?". PMID- 7985656 TI - Re: "Should we consider a subject's knowledge of the etiologic hypothesis in the analysis of case-control studies?". PMID- 7985657 TI - "Farming and prostate cancer mortality". PMID- 7985658 TI - Heterogeneity of melanoma risk in families of melanoma patients. AB - While it is recognized that relatives of melanoma patients are at increased risk for this disease, the source and extent of variation in melanoma risk between families of melanoma cases is unknown. Heterogeneity of familial melanoma risk was assessed among the families (comprising 7,666 first-degree relatives) of 1,149 cutaneous melanoma cases diagnosed in Queensland, Australia, between 1982 and 1987. The measure of familial melanoma risk was based on the number of cases of melanoma in the family in excess of those predicted from the age-, sex-, and birth cohort-specific cumulative incidences of melanoma among all relatives in the sample. Probands over-reported melanoma occurrence among their relatives, with a false positive reporting rate of 44.5% (216 false reports out of 485). Only medically verified cases among relatives were included in the analysis. There was statistically significant heterogeneity in family risk, with 53 (4.7%) of the total 1,116 unrelated families containing significantly more melanoma cases than expected considering the size of the family, and the age, sex, and birth cohort distributions of family members. In univariate analyses, members of the high-risk families were significantly more likely to have poor ability to tan, a propensity to sunburn, fair skin color, red hair, and many melanocytic nevi. When all variables were included simultaneously in a multiple logistic regression model, only the associations with tanning ability, skin color, and number of nevi remained significant. There were no significant differences overall between high-risk and other families in the sites and ages at diagnosis of melanoma, although melanomas on variably sun-exposed sites (trunk and legs) were diagnosed earlier in the high-risk families, independent of the stage at diagnosis. PMID- 7985659 TI - Risk of premenopausal breast cancer and use of electric blankets. AB - Electric blanket use, estimated to significantly increase background exposure to 60-Hz electromagnetic fields, has been hypothesized to increase breast cancer risk. From 1986 to 1991 in western New York State, the authors investigated the use of electric blankets as a risk factor for breast cancer in a case-control study of premenopausal women. A total of 290 premenopausal breast cancer cases and 289 age-matched randomly selected community controls were queried in regard to their use of electric blankets in the previous 10 years, including frequency of use in season and mode of use. After adjusting for age, education, and other risk factors, the odds ratio for use of an electric blanket at any time in the previous 10 years (40% of cases and 37% of controls) was 1.18 (95% confidence interval (CI) 0.83-1.68). Estimates of risk did not differ in a dose-response fashion for number of years of electric blanket use. The risk associated with daily use in season relative to nonuse was 1.27 (95% CI 0.86-1.88). The risk of breast cancer among those who reported use of the blanket through the night was 1.43 (95% CI 0.94-2.17). However, the risk for those who reported daily use in season, continuously throughout the night for the previous 10 years was 1.10 (95% CI 0.59-2.05). These findings do not support the hypothesis that electric blanket use is associated with an increased risk for breast cancer. Studies with improved measures of more highly exposed individuals with quantification of total electromagnetic field exposure might clarify the uncertainties regarding risk of breast cancer associated with such exposure. PMID- 7985660 TI - Alcohol consumption and breast cancer: estrogen receptor status and histology. AB - Data from a case-control study conducted in New York State during 1982-1984 were used to evaluate the relation between alcohol consumption and estrogen receptor positive and estrogen receptor-negative breast cancers and alcohol and various histologic subtypes. The cases were women between 20 and 79 years of age with a diagnosis of primary breast cancer. A total of 794 estrogen receptor-positive and 358 estrogen receptor-negative breast cancer cases were available for study. Controls (n = 1,617) were selected from driver's license files of the New York State Department of Motor Vehicles. Information on estrogen receptor status and histology was obtained from hospital records. The risk of estrogen receptor positive breast cancer was shown to increase with increasing amounts of alcohol consumption in grams per day (odds ratio (OR) = 1.18 (95% confidence interval (CI) 0.88-1.57) for < 1.5 g/day, 1.28 (95% CI 0.91-1.80) for 1.5-4.9 g/day, 1.28 (95% CI 0.96-1.70) for 5.0-14.9 g/day, and 1.35 (95% CI 0.99-1.85) for > or = 15.0 g/day). There was no relation between alcohol consumption and estrogen receptor-negative tumors (OR = 0.92 (95% CI 0.62-1.36) for < 1.5 g/day, 1.19 (95% CI 0.77-1.83) for 1.5-4.9 g/day, 0.94 (95% CI 0.64-1.35) for 5.0-14.9 g/day, and 1.05 (95% CI 0.70-1.59) for > or = 15.0 g/day). The risk for each of the histologic subtypes studied increased with increasing daily alcohol consumption. These findings suggest that alcohol may only increase a woman's risk of estrogen receptor-positive breast cancers. PMID- 7985662 TI - Influence of co-morbidity on mortality and morbidity in patients treated with hemodialysis. AB - It has been established that mortality among US end-stage renal disease patients is higher than in many other developed countries. The explanation for this apparent difference in outcome results has caused considerable concern. The explanations for this difference are complex and could include differences in case mix as well as indices of severity of illness. To evaluate potential patient based explanations for these discrepancies, we have evaluated existing reports as well as the available database at the Regional Kidney Disease Program at Hennepin County Medical Center, with particular emphasis on medical co-morbidity present in US end-stage renal disease patients. These data indicate that increasing age, a greater prevalence of diabetes mellitus patients, and a greater proportion of end-stage renal disease patients with complex medical co-morbidity contribute to the higher mortality seen in US patients receiving hemodialytic therapies. PMID- 7985661 TI - Effect of nutrition on morbidity and mortality in maintenance dialysis patients. AB - Protein-calorie malnutrition is common in maintenance dialysis patients. Malnutrition is mild to moderate in approximately 33% of maintenance dialysis patients and severe in approximately 6% to 8%. There are many causes of protein calorie malnutrition in maintenance dialysis patients; the three major causes are probably low nutrient intakes, intercurrent or underlying illnesses, and the dialysis procedure itself. Malnutrition is a major risk factor for mortality in maintenance dialysis patients. This has been shown most clearly for serum albumin, which is the nutritional parameter that has been most heavily studied. Low dietary of protein or other nutrients and protein-calorie malnutrition revealed by the results of different chemistry analyses are also directly correlated with mortality rates. These data do not prove that poor nutritional intake or malnutrition is a cause of the high morbidity and mortality in maintenance dialysis patients, and randomized, prospective controlled clinical trials are necessary to answer this question. However, the data are consistent with the thesis that malnutrition or inadequate nutrient intake do contribute to high morbidity and mortality in these patients. Although it is possible that increasing the dose of dialysis (eg, Kt/V) will lead to increased appetite and nutrient intake, experience suggests that raising the dose of dialysis, by itself, will not optimize nutritional intake in these individuals. To achieve satisfactory nutritional intake and healthy nutritional status, other interventions will need to be developed. PMID- 7985663 TI - Role of bioincompatibility in dialysis morbidity and mortality. AB - This review examines the mechanisms by which bioincompatibility in dialysis systems may have an effect on morbidity and mortality in the dialysis population. Direct toxic effects of membrane materials and various chemical substances have been well demonstrated in the chronic dialysis population. Activation of the complement cascade and stimulation of cytokine production may have autocrine effects on leukocyte function with sequelae such as enhanced rates of infection and the development of B2-microglobulin amyloidosis. The variable effect of different membrane materials on each of these effector systems is examined. Bioincompatibility may effect the incidence of infection, malignancy, cardiopulmonary disease, and malnutrition as well as induce novel disease processes. All these confounding variables must be considered when evaluating the effect of dialysis on mortality and morbidity. PMID- 7985664 TI - Hypertension in pregnancy: the incidence of underlying renal disease and essential hypertension. AB - The objective of this study was to ascertain the likelihood of underlying renal disease or essential hypertension in women diagnosed antepartum as having pre eclampsia. One hundred eighty-six women (antepartum diagnosis of pre-eclampsia in 87 women and gestational hypertension, also known as "mild pre-eclampsia" by other definitions, in 99 women) in whom no underlying disorder was apparent during pregnancy or the early puerperium were entered into the study. Women were reviewed between 3 and 60 months postpartum. All patients were assessed by measurement of blood pressure, urinalysis, and phase-contrast urine microscopy, and those with pre-eclampsia also had plasma urea, electrolyte, and creatinine concentrations determined and underwent renal imaging with either intravenous pyelography or ultrasound. The kidneys were also imaged in the gestational hypertension group if there was any clinical suspicion of underlying renal disease on review. Essential hypertension was diagnosed if systolic blood pressure was higher than 140 mm Hg and/or diastolic blood pressure was higher than 90 mm Hg after 3 months postpartum and the results of other investigations were normal. Renal disease was diagnosed in the presence of abnormal findings on urinalysis, urine microscopy, or renal imaging, or by elevated plasma creatinine concentration. Seven (8%) of the 87 women with pre-eclampsia had underlying disease (essential hypertension, five patients; renal disease, two patients [one with reflux nephropathy and one with medullary sponge kidney]), as did 16 (16%) of the 99 women with gestational hypertension (essential hypertension, 14 patients (14%); renal disease, two patients (2%) [one with medullary sponge kidney and one with thin basement membrane disease]).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7985665 TI - Increased immunoglobulin A and immunoglobulin A1 cells in bone marrow trephine biopsy specimens in immunoglobulin A nephropathy. AB - The origin of mesangial immunoglobulin A (IgA) in IgA nephropathy remains unknown. To investigate potential abnormalities within the bone marrow in this condition, bone marrow trephine biopsy specimens from seven patients and matched controls were studied using two-color immunofluorescence. In addition, serum levels of IgA and IgA1 were determined by radial immunodiffusion. Serum levels of IgA and IgA1 were higher in patients than in controls (4.53 +/- 1.38 g/L v 2.56 +/- 1 g/L, P < 0.01 and 3.68 +/- 1.11 g/L v 1.92 +/- 0.7 g/L, P < 0.005, respectively). In addition, patient trephine biopsy specimens contained an increased percentage of IgA plasma cells (61.6% +/- 4.4%) compared with controls (47.3% +/- 2.5%) (P < 0.02). The proportion of IgA plasma cells bearing subclass IgA1 was also greater in the patient biopsy specimens (91.6% +/- 1.9%) compared with controls (81.4% +/- 2.7%) (P < 0.01). In patients a positive correlation between the percentage of marrow IgA plasma cells and serum IgA levels was found (r = 0.94, P < 0.002). However, our studies failed to demonstrate a similar correlation between serum IgA1 levels and IgA1 marrow cells. These findings support the hypothesis that mesangial IgA may derive from the bone marrow. PMID- 7985666 TI - Calcium oxalate stone agglomeration reflects stone-forming activity: citrate inhibition depends on macromolecules larger than 30 kilodalton. AB - To evaluate the clinical utility of in vitro calcium oxalate monohydrate (COM) crystallization kinetics measurements and to determine the effect of quantitative removal of urinary Tamm-Horsfall glycoprotein on such measurements, we examined 24-hour, room temperature urine collections of patients from our Stone Clinic and of normal subjects from our research laboratories at Ochsner Medical Institutions in New Orleans, LA, and compared their COM kinetic parameters in vitro before and after urine ultrafiltration (30 kd). Data from 53 calcium oxalate stone-forming patients (26% women; mean age, 47 years) who demonstrated radiographic or other evidence of forming at least one stone were compared with data from 22 healthy volunteers (25% women; mean age, 40 years). Hypercalciuria (> 7.5 mm/24 hr), hyperoxaluria (> 0.5 mm/24 hr), and hypocitraturia (< 2.0 mm/24 hr) were present in 38%, 26%, and 26% of the patient population, respectively. Urinary creatinine, urate, calcium, citrate, phosphate, oxalate, pH, volume, total immunoreactive disaggregated Tamm-Horsfall glycoprotein, and the urine's effects on COM solubility, percent crystal growth inhibition, and crystal agglomeration inhibition [tm] were determined. Calcium oxalate monohydrate agglomeration inhibition, [tm], was reduced in stone-forming patients. It decreased with increasing stone frequency, making [tm] a useful tool for measuring the risk of stone recurrence. Urinary Tamm-Horsfall glycoprotein and citrate concentrations were linearly related to COM agglomeration inhibition. Their effects were synergistic. Tamm-Horsfall glycoprotein removal from urine reduced COM agglomeration inhibition dramatically. Alkali therapy increased urinary citrate concentration and increased [tm].(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7985667 TI - Lack of efficacy of angiotensin-converting enzyme inhibitors in reducing interdialytic weight gain. AB - Angiotensin-converting enzyme inhibitors (ACEIs) have been suggested to reduce interdialytic fluid weight gain, presumably via suppression of the dipsogenic angiotensin II. We retrospectively studied 25 (76% black) chronic hemodialysis patients who received ACEIs for blood pressure control. The mean arterial blood pressure decreased from 115.4 +/- 10.4 mm Hg to 112.7 +/- 9.0 mm Hg (mean +/- SD; P = NS) and there was no change in the interdialytic weight gain (3.74 +/- 1.5 kg v 3.72 +/- 1.5 kg; P = NS). Only 10 (40%) patients had some reduction in their interdialytic weight gain; in four of them the reduction was more than 20% of the pre-ACEI weight gain. When nine patients who had no decline in blood pressure were excluded due to possible noncompliance, the mean arterial blood pressure in the remaining 16 patients (75% black) declined from 119.3 +/- 9.9 mm Hg to 111.6 +/- 9.9 mm Hg (P < 0.0001), but there was no change in the interdialytic fluid weight gain (3.7 +/- 1.4 kg v 3.8 +/- 1.4 kg; P = NS). There was no correlation between age, race, etiology of renal failure, or blood pressure response and change in the interdialytic weight gain after ACEI treatment. Our results do not support the previous report that ACEIs significantly decrease the interdialytic weight gain in chronic hemodialysis patients. The multifactorial nature of excessive fluid intake in the hemodialysis patients and the differences in patient population and study design may account for this discrepancy. PMID- 7985668 TI - The association of intradialytic parenteral nutrition administration with survival in hemodialysis patients. AB - Hemodialysis patients who had received intradialytic parenteral nutrition (IDPN) during 1991 were identified. These patients were compared with unexposed controls after adjusting for demographic variables, baseline renal diagnosis, diabetic status, serum albumin (ALB), creatinine (CRE), and urea reduction ratio. At lower levels of ALB (< or = 3.4 g/dL), treatment with IDPN was associated with a reduction in the odds of death at 1 year, an effect that became stronger at lower levels of CRE (< or = 8.0 mg/dL). In contrast, treatment with IDPN in patients with normal ALB was associated with increased mortality. Time trend analyses of ALB and CRE demonstrated progressive increases toward pretreatment levels in IDPN recipients that were not evident in control subjects. These time trend data suggest that in undernourished hemodialysis patients, IDPN can effect the serum levels of valid biochemical surrogates of visceral and somatic protein nutrition. Albeit retrospective, the improvement in survival at year's end among patients with ALB < or = 3.4 g/dL suggests that malnutrition and its attendant ill effects in hemodialysis patients may respond to aggressive therapeutic intervention, such as IDPN. These important findings should be prospectively confirmed in a randomized clinical trial. PMID- 7985669 TI - Deficiencies in delivered hemodialysis therapy due to missed and shortened treatments. AB - The frequency of missed and shortened hemodialysis treatments was assessed in a randomly selected sample of 860 ESRD patients from 54 dialysis units. Data were collected for three sequential 4-week periods covering 28,108 treatments. During each of these 4-week periods, 5.1% to 7.6% of patients missed at least one treatment, 26.8% to 32.3% of patients had at least one shortened treatment, and 6.6% to 7.9% of patients missed 10% or more of their prescribed therapy. Over the entire 12-week period, 50% of patients had either missed or shortened treatments (or both). Missed and shortened treatments are prevalent enough to account for clinically important deficiencies in delivered dialysis for a significant number of patients. PMID- 7985670 TI - The effect of dialyzer reuse on dialysis delivery. AB - It is well documented that the reprocessing of dialyzers may reduce their solute clearance capabilities. However, the effect of dialyzer reuse has never been assessed in an uncontrolled clinical practice setting. We addressed this issue in a prospective 436-patient, 34-center study. All patients underwent formal urea kinetic modeling monthly, usually for 3 sequential months. Dialyzers were reprocessed and reused in the usual manner for each unit. As a result, urea kinetic modeling was performed in individual patients using dialyzers with differing numbers of prior uses. For each patient, Kt/V urea for the treatment using the dialyzer with the most reuses (mean, 13.8) was compared with that with the treatment using the dialyzer with the fewest reuses (mean, 3.8). The mean Kt/V delivered for high reuse treatments was significantly lower than that for low reuse treatments (1.05 v 1.10, P = 0.002). Prescribed Kt/V in high and low reuse treatments was identical. Individual centers appeared to differ substantially (P = 0.06) in the effect of reuse on delivered Kt/V. Of the 23 centers using formalin-based reprocessing, an average difference of > or = 0.12 (mean, 0.17) in Kt/V between high and low reuse treatments was seen in 10 centers. Dialyzer reprocessing significantly impairs dialysis delivery, an effect that may be related to the methods and procedures in individual dialysis centers. PMID- 7985671 TI - Glomerular barrier function following conversion from cyclosporine to azathioprine in renal transplant recipients. AB - The renal side effects are the major limitation of the use of cyclosporine in clinical transplantation. We studied the reversibility of changes in renal hemodynamics and glomerular barrier function in 17 patients with moderately impaired renal function at least 1 year after kidney transplantation. All patients were studied both during cyclosporine treatment and 3 months after conversion to azathioprine. During azathioprine treatment both glomerular filtration rate and effective renal plasma flow increased significantly (from 44.3 +/- 4.2 mL/min to 63.5 +/- 5.4 mL/min and from 192 +/- 12.8 mL/min to 260 +/ 14.6 mL/min, respectively). Despite the marked changes in renal hemodynamics, no significant changes were observed in the fractional clearances of uncharged dextrans. When calculating the characteristics of the filtration barrier, we observed a trend toward an increase in the ultrafiltration coefficient (Kt). This trend was abolished when an increase in net filtration pressure (delta P) was assumed to result from reduced prerenal vasoconstriction. We conclude that despite marked improvement of renal perfusion and glomerular filtration, conversion from cyclosporine to azathioprine did not significantly alter the permeability characteristics of the glomerular filtration barrier in renal transplant recipients with moderately reduced renal function. Improvement in renal function following conversion could result from an increase in either Kf or delta P. Since renal plasma flow was increased significantly, the observed improvement in glomerular filtration rate is likely to be, at least in part, due to an increase in glomerular capillary plasma flow. PMID- 7985672 TI - Acute muscular paralysis in an adult with subclinical Bartter's syndrome associated with gentamicin administration. AB - We report an adult case of asymptomatic Bartter's syndrome with the first presentation of hypokalemic paralysis triggered by gentamicin injection. Marked hypokalemia and hypomagnesemia associated with excessive kaliuresis and magnesiuria were found. Plasma renin activity and aldosterone concentration were high, but blood pressure was normal. Renal biopsy revealed hypercellularity of the renin-producing cell of the juxtaglomerular apparatus. Muscular paralysis subsided after potassium chloride supplementation. Hypokalemia was corrected with potassium and magnesium supplements and the use of diclofenac. To the best of our knowledge, there have been no reports of muscular paralysis associated with gentamicin in Bartter's syndrome. PMID- 7985673 TI - Familial hemolytic-uremic syndrome and homozygous factor H deficiency. AB - Inherited hemolytic-uremic syndrome (HUS) is unusual. We report the occurrence of HUS in two siblings; one died at an early age while the other (the proband) has presented with three episodes of HUS since the age of 19 years. The finding of a persistently low serum C3 level in this patient led to a thorough evaluation of her complement cascade and a family investigation. The proband and her asymptomatic younger sister were found to have very low serum levels (5% of normal) of factor H, a regulatory protein of the alternative complement pathway. Both patients had low levels of serum C3, factor B, CH50 and VAH50, reflecting persistent alternative pathway activation. The father and mother both had half normal serum factor H levels but an otherwise normal complement profile. Other members of the extended pedigree were also found to have half-normal serum factor H levels. In conclusion, in this family, factor H deficiency appears to be associated with HUS and is transmitted as an autosomal recessive trait. Persistent C3 hypocomplementemia in the setting of familial and/or recurrent HUS should be a clue to a possible inherited complement deficiency. PMID- 7985674 TI - Lipoprotein glomerulopathy: first report in a Chinese male. AB - Only seven patients with lipoprotein glomerulopathy have been reported, all in Japanese subjects. We describe the first Chinese patient with lipoprotein glomerulopathy, a 28-year-old man followed for 8 years. As in all patients described thus far, our patient has hyperlipoproteinemia phenotypically similar to the familial type III hyperlipoproteinemia, a high serum level of apolipoprotein E (apo E) (but with the heterozygous E 2/3 isoform instead of the E 2/2 isoform), and the absence of the typical clinical features associated with type III hyperlipoproteinemia. The common clinical presentation is the nephrotic syndrome. The characteristic pathologic features are concentrically layered vacuolated lipid "thrombi" in distended glomerular capillary lumens that contain beta/pre-beta lipoprotein. Immunofluorescence studies demonstrate lipoprotein "thrombi" staining for apo E and apo B, but not apo A-I, apo A-II, or apo J. Immunoglobulins, complement, and fibrin are absent or present in trace amounts. The long-term follow-up demonstrates progressive deterioration of renal function despite lipolytic therapy. The apparent predilection of lipoprotein glomerulopathy in Orientals, particularly Japanese subjects, is poorly understood, but appears to be related to genetic factors. The cause of the hyperlipoproteinemia and lipoprotein "thrombi" containing apo E and apo B is unknown, but is possibly related to defective receptor-binding mechanisms. PMID- 7985675 TI - Secondary hyperparathyroidism, and not beta 2-microglobulin amyloid, as a cause of spontaneous tendon rupture in patients on chronic hemodialysis. AB - Spontaneous bilateral rupture of the extensor mechanisms of the knees, without significant history of trauma, has been reported rarely, generally in association with chronic metabolic disorders, such as chronic renal failure and secondary hyperparathyroidism. We report spontaneous tendon rupture in two patients on chronic hemodialysis for 4 and 11 years, with documented severe secondary hyperparathyroidism. One patient had spontaneous bilateral rupture of his quadriceps and partial avulsion of the left triceps tendons. The other patient had spontaneous rupture of his right quadriceps tendon. Both patients had markedly elevated serum intact parathyroid hormone and moderately elevated serum beta 2-microglobulin levels. Pathologic examination revealed diffuse immunohistochemical staining for beta 2-microglobulin but negative Congo-red staining of the ruptured tendon specimens. These cases and the previous reports in the literature suggest that secondary hyperparathyroidism may play a role in the pathogenesis of this clinical entity. PMID- 7985676 TI - Nephritic factors predispose to chronic glomerulonephritis. AB - Chronic glomerulonephritis has been reported in three rare conditions in which factor H of the complement system does not function normally. Factor H is essential for the inactivation of the C3b-dependent convertase, C3b,Bb, which is constantly being formed in vivo. With factor H dysfunction, this convertase accumulates and produces hypocomplementemia. Twenty-two individuals have been reported with the three forms of H dysfunction, and 12 have displayed evidence of chronic glomerulonephritis. In addition, matings of certain Yorkshire pigs result in offspring that are homozygous deficient in factor H and have a high incidence of a severe hypocomplementemic glomerulonephritis closely resembling membranoproliferative glomerulonephritis type II. The hypothesis proposed is that the nephritis that develops with these forms of H dysfunction is in some way the result of circulating convertase. The corollary is that nephritic factors, also producing H dysfunction and higher than normal circulating levels of the C3b dependent convertase, are responsible for the glomerulonephritides with which they are associated, mainly membranoproliferative glomerulonephritis types II and III. Nephritic factors are autoantibodies that bind to the C3b-dependent convertase and render it resistant to dissociation by factor H. Although nephritic factors are currently considered epiphenomena, their role in the pathogenesis of membranoproliferative glomerulonephritis should be reconsidered based on the evidence that circulating convertase is nephritogenic. PMID- 7985677 TI - Are nephritic factors nephritogenic? PMID- 7985678 TI - Recommendations for reducing the high morbidity and mortality of United States maintenance dialysis patients. The National Kidney Foundation. PMID- 7985679 TI - Hemodialysis therapy in the United States: what is the dose and does it matter? AB - There is an ongoing discussion in the renal community about how to monitor the treatment of hemodialysis patients in the United States. Comparison of the US patient experience to that of other countries with populations of similar health status is one way to assess treatment. Another technique involves examining the level of dialysis therapy US patients receive. This paper reviews recent studies which found that the United States has higher mortality than both Japan and Europe and provides additional information as to why those comparisons might be underestimating the mortality differences. We also examine the data on the level of dialysis US patients receive, both as a prescription and as delivered care. We conclude that US patients receive less hemodialysis therapy than their European and Japanese counterparts, and that in general US patients are not receiving the level of dialysis they were prescribed. These factors are correlated with an increased mortality among US hemodialysis patients. PMID- 7985680 TI - Role of dialysis dose on morbidity and mortality in maintenance hemodialysis patients. AB - The United States dialysis population has an excessive mortality rate that cannot be fully explained by comorbid conditions or demographic factors. The quantity of dialysis has been suggested to be insufficient. This report reviews the several dialysis-related factors that impact on mortality. Since the National Cooperative Dialysis Study in 1983, there have been no controlled trials. However, numerous retrospective and two recent larger prospective studies indicate that increasing the quantity of dialysis by 40% to 50% of that traditionally provided in the United States will significantly improve survival. This is equivalent to a Kt/V of less than 1.2 and possibly less than 1.4 using single pool urea kinetics. It is estimated that this would save an additional 8,000 to 16,000 lives per year. PMID- 7985681 TI - Adequacy of continuous ambulatory peritoneal dialysis: morbidity and mortality in chronic peritoneal dialysis. AB - Mortality for hemodialysis patients tends to be in excess of 20% per year, and it is generally agreed that outcome for continuous ambulatory peritoneal dialysis patients is comparable. Several investigators have suggested recently that continuous ambulatory peritoneal dialysis, as commonly practiced, may not provide adequate therapy, especially for larger patients and for those with no residual renal function. Unfortunately, a dose-response curve relating the amount of dialysis delivered and clinical outcome for continuous ambulatory peritoneal dialysis patients has not been constructed. Several methods of quantifying the dose of peritoneal dialysis are described. Both cross-sectional and longitudinal studies are reviewed. The conclusions of these studies are of limited value, however, because of their retrospective nature and the limited number of patients enrolled. Nevertheless, in aggregate, these studies suggest that survival may be improved by higher doses of dialysis. They also suggest that while malnutrition is relatively common in this patient population, higher doses of Kt/V are associated with higher protein intake (as measured by protein catabolic rate). Serum albumin is recognized as a strong predictor of clinical outcome and the protein catabolic rate may correlate directly with Kt/V, but there are studies that support and others that refute a correlation between Kt/V and serum albumin. Definitive answers to these questions are likely to be available in the near future. Two large multicenter studies are currently under way. Preliminary results may be available in the near future. PMID- 7985682 TI - Diagnostic and treatment mistakes add to costs of heart failure care. PMID- 7985683 TI - Stavudine approved under accelerated drug-approval process. PMID- 7985684 TI - Misrepresenting an ASHP practice standard for commercial purposes. PMID- 7985685 TI - When the prescription says "leeches". PMID- 7985686 TI - Preserving pharmacy's public image. PMID- 7985687 TI - Creatinine-clearance estimates for predicting gentamicin pharmacokinetic values in obese patients. AB - The Cockcroft-Gault and Salazar-Corcoran equations were compared with respect to prediction of gentamicin pharmacokinetic values in obese and nonobese patients, and the results were used to formulate guidelines for calculating initial gentamicin dosages in obese patients. Creatinine clearance (CLcr) was estimated by applying the Cockcroft-Gault equation using total body weight (TBW), ideal body weight (IBW), and dosage weight (DW) and with Salazar-Corcoran equations using fat-free body mass (FBM) in 100 obese and 100 nonobese patients. Gentamicin pharmacokinetic values (k, CL, and t1/2) were estimated by using CLcr estimated by each method and standardized to a body surface area of 1.73 sq m. Actual pharmacokinetic values were determined by using steady-state gentamicin concentrations and a modified Sawchuk-Zaske equation; these values were compared with the predicted values. In the obese patients, pharmacokinetic values predicted from standardized CLcr by the Cockcroft-Gault equation using estimated DW were not significantly biased, compared with actual values; most predictions produced by the other methods were significantly biased. Predictions produced by the DW method were generally more precise than those resulting from the other methods. In nonobese patients, k values estimated by the Cockcroft-Gault equation using IBW were not significantly biased, while values obtained with all other methods were biased. All methods were biased when predicting CL and t1/2 in nonobese patients. Significant correlations existed between standardized estimates of CLcr (by all methods) and pharmacokinetic values in both groups. Predictions of gentamicin k, CL, and t1/2 were best overall when CLcr was estimated by the Cockcroft-Gault equation using DW, rather than by other methods.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7985688 TI - Computerized documentation of pharmacists' interventions. AB - A computerized system for documenting interventions, developed by the pharmacy department at a 695-bed tertiary care university teaching hospital, is described. A computerized system was developed to better gain the needed details on pharmacists' recommendations, to capture a greater number of such recommendations, and to prepare for recent changes in standards of the Joint Commission on Accreditation of Healthcare Organizations. Only clinically important recommendations or those that involve cost savings are documented. Data can be entered and retrieved from any medical information system terminal in the hospital, and each entry becomes part of the patient's permanent record. A hard copy of all recommendations and a data file are generated daily. Analysis of the data has provided numerous opportunities for improving both patient care and the quality of pharmaceutical services. The system has been well received by pharmacists and has resulted in physician support of pharmacists' recommendations, as well as substantial cost savings. A convenient, easy-to-use computerized program for reporting interventions has helped a pharmacy department conduct departmental and institutional quality assurance activities and decrease costs. PMID- 7985689 TI - Stability of labetalol hydrochloride with selected critical care drugs during simulated Y-site injection. AB - The compatibility and stability of labetalol hydrochloride in combination with various critical care drugs was evaluated. Labetalol hydrochloride 1.0 mg/mL was combined in 5% dextrose injection with equal volumes of each of the following drugs: dobutamine 2.5 mg/mL (as the hydrochloride salt), dopamine hydrochloride 1.6 mg/mL, morphine sulfate 0.5 mg/mL, nitroglycerin 0.2 mg/mL, and ranitidine 0.6 mg/mL (as the hydrochloride salt). The mixtures were placed in duplicate Y site administration sets. Visual inspection, pH determination, and high performance liquid chromatography were performed in duplicate on samples removed at zero, two, and four hours. No change in pH or appearance occurred throughout the study. All drug concentrations remained above 90% of the initial concentration in each combination. Labetalol hydrochloride 1.0 mg/mL and dobutamine 2.5 mg/mL (as the hydrochloride salt), dopamine hydrochloride 1.6 mg/mL, morphine sulfate 0.5 mg/mL, nitroglycerin 0.2 mg/mL, or ranitidine 0.6 mg/mL (as the hydrochloride salt) in 5% dextrose injection were stable and compatible for up to four hours at 20-25 degrees C during simulated Y-site injection. PMID- 7985690 TI - Metropolitan network of drug-use evaluation and quality assurance pharmacists. PMID- 7985691 TI - Updated bedside charts for calculating pediatric doses of emergency medications. PMID- 7985692 TI - Pharmacist adjustment of H2-receptor antagonist dosage to meet medical staff approved criteria. PMID- 7985693 TI - Pharmacist-directed program for monitoring foscarnet therapy. PMID- 7985694 TI - Stability of diluted methylprednisolone sodium succinate injection at two temperatures. PMID- 7985695 TI - Stability of ceftriaxone sodium in injectable solutions stored frozen in syringes. PMID- 7985696 TI - High-performance liquid chromatography for small-scale studies of drug stability. AB - The fundamentals of high-performance liquid chromatography (HPLC), as applied in small-scale studies of drug stability, are presented. Chromatography is the separation of a complex mixture into its individual compounds through partitioning between a mobile phase and a stationary phase. A high-performance liquid chromatograph consists of mobile-phase reservoirs, pumps, a mixer to mix the solvents, a valve into which the sample is injected, a guard column, a column containing the stationary phase, a detector, and a recorder. Once compounds have been separated in the column, they pass into the detector, where an electronic signal corresponding to the amount of compound present is recorded as a peak in a chromatogram. The most common detection method is ultraviolet and visible light spectroscopy. Key concepts in HPLC theory are retention time, the time from injection of the sample to detection of a peak; capacity factor, a measure of retention corrected for the elution of an unretained compound; resolution, a measure of how well two peaks are separated; the selectivity of the method; efficiency, or resolving power; and the degree of symmetry of the peaks produced. Most HPLC separations are performed in the reverse-phase mode, which involves a nonpolar stationary phase and a largely polar mobile phase. Other modes are normal phase, ion exchange, and size exclusion. Before a drug stability study is carried out, an HPLC method must be developed that suits the needs of the proposed experiment. A thorough literature search is essential. Literature procedures serve as useful starting points but may require a great deal of manipulation. After the HPLC separation has been performed, it is necessary to validate the method used. It must be proved that the method is stability indicating, that the chromatographic standards were properly prepared, that the standard curve is acceptable, and that the method is both precise and accurate. Pharmacists who ensure that reliable, reproducible HPLC methods are used throughout studies of drug stability will obtain sound data that may be of great value in pharmacy practice. PMID- 7985697 TI - Hospital's independent responsibility to obtain informed consent. PMID- 7985698 TI - Summary of the final report of the Scope of Pharmacy Practice Project. PMID- 7985699 TI - Beyond pharmaceutical care. PMID- 7985700 TI - Criteria for use of cladribine in adults. PMID- 7985701 TI - Antiretroviral therapy during pregnancy. PMID- 7985702 TI - A hospital in rural Zimbabwe: and we think we have problems here. PMID- 7985703 TI - Relative costs of granisetron and ondansetron. PMID- 7985704 TI - Stability of cefazolin sodium-famotidine admixture. PMID- 7985705 TI - More on prophylaxis with aztreonam plus metronidazole during appendectomy. PMID- 7985706 TI - Long-term impact of initial and surgical therapy on papillary and follicular thyroid cancer. PMID- 7985707 TI - Efficacy of dietary fiber in lowering serum cholesterol. PMID- 7985708 TI - Long-term treatment of hypercholesterolemia with dietary fiber. AB - PURPOSE: To evaluate the hypocholesterolemic effects of long-term treatment (36 to 51 weeks) with a mixture of dietary fibers (guar gum, pectin, soy, pea, corn bran) administered twice a day. PATIENTS AND METHODS: Fifty-nine subjects with moderate hypercholesterolemia who completed a 15-week, placebo-controlled study with the dietary fiber were treated for an additional 36 weeks with 20 g/day of fiber. Subjects were counseled and monitored on a National Cholesterol Education Program (NCEP) Step-One Diet before starting and during treatment. Analyses of changes in lipoprotein values during the additional 36 weeks of treatment took into account changes in weight, diet, and other variables that might have affected the response to treatment. RESULTS: There were no significant effects on the levels of either triglycerides or high-density lipoprotein cholesterol (HDL C). Levels of total cholesterol (TC) and low-density lipoprotein cholesterol (LDL C) and the LDL/HDL ratio were significantly reduced during treatment. The mean percentage reductions from baseline after 51 weeks of treatment were approximately 5% for TC, 9% for LDL-C, and 11% for the LDL/HDL ratio. Changes were apparent after 3 weeks of treatment, with the maximum reductions occurring by the 15th week of treatment. CONCLUSIONS: For subjects on a Step-One Diet who complied with the treatment regimen, the moderate cholesterol-lowering effects of the fiber persisted throughout the 36-to-51 week treatment period. PMID- 7985710 TI - The continuing utility of bronchoalveolar lavage to diagnose opportunistic infection in AIDS patients. AB - PURPOSE: To determine whether bronchoalveolar lavage (BAL) remains a useful technique in assessing human immunodeficiency virus (HIV)-infected patients with pulmonary symptoms. PATIENTS AND METHODS: All HIV-infected patients with pulmonary symptoms referred to a university hospital-based pulmonary service underwent bronchoscopy and BAL within 24 hours of referral. All samples were handled in a standardized fashion. The results of the lavage were compared with chest roentgenograms and clinical results. RESULTS: A total of 894 lavages were performed on HIV-infected patients over a 7-year period. The overall diagnostic yield was 60%, with 420 patients having Pneumocystis carinii. Infections other than P carinii were found in 185 cases, including 75 lavages with P carinii and another infection. The other infections included Mycobacterium tuberculosis (17 patients), Mycobacterium kansasii (15 patients), Histoplasma capsulatum (24 patients), Cryptococcus neoformans (17 patients), and bacterial infection (103 patients). For 364 lavages, no diagnosis was made. Chest roentgenograms were not useful in predicting what infection would be diagnosed. There was no difference in the yield of BAL over the 7-year period, despite the introduction of aerosol pentamidine prophylaxis and antiretroviral therapy. CONCLUSION: Bronchoscopy with BAL continues to have a role in the evaluation of HIV-infected patients with pulmonary symptoms. PMID- 7985709 TI - The prophylactic use of low-dose amphotericin B in bone marrow transplant patients. AB - PURPOSE: To evaluate the efficacy of prophylactic low-dose amphotericin B (0.1 mg/kg per day) (LDA) in preventing fungal infections in patients who have had a bone marrow transplant (BMT). MATERIALS AND METHODS: Double-blind, randomized, controlled trial in which patients undergoing bone marrow transplantation received intravenous LDA or similar-appearing placebo from the onset of neutropenia until the absolute neutrophil count remained > 0.5 x 10(9)/L, or until high-dose amphotericin B was initiated. Weekly surveillance cultures were obtained from all patients. RESULTS: Five of 18 patients (28%) randomized to placebo developed documented systemic fungal infections within the first 30 days after transplantation, compared to none of 17 patients who received LDA (P = 0.045). LDA recipients received fewer days of high-dose amphotericin B (P = 0.04) and fewer days of antibiotics (P = 0.008). There were trends towards fewer days of hospitalization (P = 0.14) and improved survival (P = 0.08); these differences were statistically significant among recipients of allogeneic BMT. No adverse effects occurred with LDA therapy. CONCLUSIONS: LDA appears to be safe and to reduce early systemic fungal infections in BMT recipients. Improved survival was observed among LDA recipients, but this was not directly attributable to the prevention of fungal infection. PMID- 7985711 TI - Vitamin A hepatotoxicity: a cautionary note regarding 25,000 IU supplements. AB - Vitamin A hepatotoxicity has been reported at doses exceeding 50,000 IU/day. At 25,000 IU vitamin A per day, although elevated liver enzymes may be seen, hepatotoxicity is rare. We report a case of severe hepatotoxicity associated with the habitual daily ingestion of 25,000 IU of vitamin A bought as an over-the counter dietary supplement. With the general availability of high-dose supplements and recent literature emphasizing the importance of vitamin A adequacy, the potential for vitamin A hepatotoxicity may increase. Health professionals should remain aware of the potential for vitamin A hepatotoxicity and elicit a vitamin A history in all patients being evaluated for liver dysfunction. PMID- 7985712 TI - Angiographic ablation of mediastinal parathyroid adenomas: local experience and review of the literature. AB - PURPOSE: To evaluate local experience with a modified technique for angiographic ablation of mediastinal parathyroid adenomas. PATIENTS AND METHODS: Three patients with likely mediastinal parathyroid adenomas that had single feeding arteries underwent attempted arteriographic ablation with a slow continuous infusion of contrast medium. Patients were closely monitored for symptoms and calcium dynamics immediately postprocedure and then on a long-term outpatient basis. RESULTS: All three patients were cured (follow-up 22 to 68 months) with no long-term complications. CONCLUSION: Percutaneous angiographic ablation with contrast medium is a reasonable alternative for patients with hyperparathyroidism due to a mediastinal adenoma who can be treated in centers with well-trained interventional radiologists. PMID- 7985713 TI - Recovery of epinephrine response but not hypoglycemic symptom threshold after intensive therapy in type 1 diabetes. AB - PURPOSE: Patients with intensively treated insulin-dependent diabetes mellitus (IDDM) exhibit more severe defects in counterregulatory hormone secretion and symptom recognition during hypoglycemia than do conventionally treated patients. In this prospective study in patients with preexisting defects in counterregulation, we examined the induction and reversibility of impaired symptomatic and adrenomedullary responses to hypoglycemia in 5 patients with IDDM (diabetes duration of 2 to 16 years; aged 19 to 36 years; 3 women, 2 men) who were receiving intensive therapy. METHODS: Counterregulatory responses were assessed by using a single-step (approximately 2.8 mmol/L plasma glucose) and multiple-step (from approximately 5 mmol/L to 2.2 mmol/L plasma glucose) clamped hypoglycemia procedure. Patients were first studied after a stable period of conventional insulin therapy (glycosylated hemoglobin [HbA1c] 9.5 +/- 1.2%), then after 3 to 5 months of intensive therapy (HbA1c 6.6 +/- 0.2%), and a third time after resuming conventional therapy (HbA1c 8.7 +/- 0.9%). RESULTS: Intensive therapy was associated with a 44% decline (P < 0.01) in the average plasma epinephrine increase during hypoglycemia, and the plasma glucose level required to stimulate epinephrine secretion fell from 3.7 +/- 0.2 to 3.0 +/- 0.1 mmol/L (P < 0.01). The threshold, but not the magnitude, of the plasma norepinephrine response was similarly altered. Hypoglycemic symptoms also decreased in intensity (by 67%, P < 0.01), and the glucose level required for symptom activation fell from 3.4 +/- 0.3 to 2.7 +/- 0.2 mmol/L, P < 0.01). When conventional therapy was resumed, the abnormalities in the epinephrine response due to intensive therapy were almost completely reversed. However, the reduction in symptoms and the altered thresholds for plasma norepinephrine were not reversed. CONCLUSIONS: There is dissociation between the treatment-associated defects in hypoglycemia counterregulation in IDDM, and an increase in average glycemia produced by a return to conventional insulin therapy is not sufficient to reverse hypoglycemia unawareness worsened by intensive therapy. PMID- 7985714 TI - POEMS syndrome: a study of 25 cases and a review of the literature. French Study Group on POEMS Syndrome. AB - OBJECTIVE: To determine whether there are peculiarities of the POEMS syndrome (a multisystemic disorder associated with polyneuropathy, organomegaly, endocrinopathy of various forms, production of a monoclonal [M] component, and skin changes) in Caucasian patients, especially signs and symptoms absent in other series; and to attempt a reappraisal of the neuropathy and endocrinopathy to find a unifying mechanism. DESIGN: A retrospective, cooperative study compared 25 cases, observed over a 15-year period, with two published series of patients, one of Japanese patients and one of American patients, and with a review of the literature on non-Asian cases. Details were obtained of patients' medical history, physical examination, immunochemical and hormonal testing, roentgenographic examination, computed tomography imaging, and electromyography. RESULTS: The main features of the syndrome found in these patients were those first described in Japan: polyneuropathy, enlargement of the lymph nodes, liver, and spleen, endocrine disturbances, low concentration of the monoclonal component, hyperpigmentation, and hypertrichosis. Three other symptoms were found more frequently than previously reported: skin angiomas, scleroderma changes of the hands, and thrombocytosis. Electromyography and nerve biopsy showed a variety of abnormalities ranging from demyelination to axonal degeneration. Nerve deposits of immunoglobulin were absent. Organomegaly seemed to be heterogeneous. Pathologic findings in the enlarged lymph nodes and spleen were compatible with Castleman's disease. Liver biopsies were usually normal. The endocrine changes were surprisingly diverse, with some observations combining unrelated primary and secondary insufficiencies. No single hypothesis emerged regarding their mechanism. All M components had a lambda-light chain. An IgG M component was found more frequently in solitary lesions. An IgA M component was found more frequently in patients without bone lesions. Sedimentation rate was usually normal. Radiotherapy of solitary plasma-cytomas was followed by dramatic improvement of extramedullary signs and symptoms in all cases. CONCLUSIONS: The symptoms, clinical course, and management of the patients reported here were similar to those observed in the literature. This study confirms the existence of a close link between symptoms and lambda-light-chain production. There are indications that a plasma cell growth factor that does not cross-react with interleukin-6 (IL-6) may be involved. PMID- 7985715 TI - Generalist physicians and the new health care system. PMID- 7985716 TI - Amphotericin B-induced dilated cardiomyopathy. PMID- 7985717 TI - Risk factors for hepatosplenic abscesses in patients with acute leukemia receiving empiric azole treatment. AB - The authors retrospectively evaluated 63 febrile neutropenic episodes in 33 consecutive patients with leukemia who received empiric azole treatment for refractory or relapsing fever that occurred despite broad-spectrum antibiotics. In 8 patients (24%), hepatosplenic abscesses (HSA) developed. To identify the risk factors for the development of HSA, the authors compared various characteristics of febrile episodes in those with and without HSA. The risk factors included relapsed status of leukemia (P = 0.04) and Candida colonization of surveillance cultures from the throat (P = 0.03) and stool (P = 0.03). However, the duration of neutropenia, gastrointestinal symptoms, types of chemotherapy, and leukemia subtypes were not correlated with the development of HSA. Based on these results, the authors identified the high risk group for the development for HSA as patients with relapsed leukemia with fungal colonization of gastrointestinal tract during neutropenia despite empiric antifungal treatment with azoles. PMID- 7985719 TI - Distinguishing between the catalytic potential and apparent expression of tyrosinase activities. AB - Assays were developed to investigate the catalytic potential and apparent expression of tyrosinase activities. Tyrosine hydroxylase activity determined with cell lysates (in vitro), entire fixed cells (postfixation), or intact living cells (in situ), and 3,4-dihydroxyphenylalanine oxidase assayed spectrophotometrically or by 3,4-dihydroxyphenylalanine staining on sodium dodecyl sulfate-polyacrylamide gel electrophoresis, demonstrated the following results: 1) The in situ assay displayed reduced tyrosine hydroxylase activity in all three tyrosinase-positive oculocutaneous albino (OCA) lines except for Chediak-Higashi Syndrome melanocytes, which displayed normal activity; 2) The in vitro assay had comparable activity of tyrosinase-positive OCA melanocytes as controls, except for one tyrosinase-positive OCA cell line, which demonstrated increased activity; 3) The postfixation assay, compared with the in situ assay, had elevated activity (ie. normalization) of tyrosinase in OCA cells but reduced activity in controls; 4) The spectrophotometric assay for 3,4 dihydroxyphenylalanine oxidase activity correlated very well with the tyrosine hydroxylase activity determined by the in vitro assay; 5) sodium dodecyl sulfate polyacrylamide gel electrophoresis of melanocyte lysates either stained with 3,4 dihydroxyphenylalanine or immunoblotted with anti-tyrosinase detected abnormal tyrosinase bands in the Chediak-Higashi Syndrome and one line of tyrosinase positive OCA melanocytes, and both lines had release of tyrosinase into the growth media. In conclusion, the selection and combination of these tyrosinase assays would be informative for differentiation and characterization of human albinism. PMID- 7985718 TI - A clinically applicable technique to study cytoskeletal dynamics in normal and abnormal polymorphonuclear leukocytes isolated from small volume blood samples. AB - Shape change and motility of polymorphonuclear leukocytes (PMNs) are essential for host defense and require dynamic reorganizations of microfilamentous cytoskeleton by reversible polymerization of G-actin into filaments (F-actin). Although clinical disorders of actin polymerization are rare, recently described simple methodologies for assaying actin dynamics in PMNs make the technique readily applicable to clinical studies. To develop a clinically useful F-actin assay, the authors investigated the optimal preparation conditions for PMN isolation that resulted in the least in vitro cytoskeletal activation and evaluated the variability in actin dynamics in acutely and chronically infected patients. Basal and chemotactic factor-activated PMN F-actin content was measured by a previously described flow cytometric technique in fixed, permeabilized, NBDphallacidin-stained PMNs isolated by centrifugation in Percoll or Ficoll Hypaque density gradients or by countercurrent elutriation. F-actin content is expressed as mean fluorescent channel or relative fluorescence intensity. Basal F actin in PMNs prepared from countercurrent elutriation (mean fluorescent channel = 79.0 +/- 4.5, n = 6) or by Ficoll Hypaque (82.0 +/- 3.5, n = 4) was significantly higher than endotoxin free, Percoll purified PMNs, whether purified in bulk (56.1 +/- 7.9, n = 8) or by the small volume modification applicable to clinical studies (53.3 +/- 8.7, n = 15). Basal Ficoll Hypaque purified PMNs have evidence of shape change, whereas endotoxin free, Percoll purified PMNs are smooth and round and represent the most basal cell equivalent in F-actin content to a circulating PMN.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7985720 TI - Intrarenal hemodynamics in low- and high-output cardiac failure in rats. AB - Cardiac failure is multifactorial in causation, and the underlying physiologic mechanisms are variable, yet their renal effects have been considered more homogeneous. To investigate and compare the intrarenal hemodynamic characteristics in two experimental types (low- and high-output) of cardiac failure, renal micropuncture studies were performed in rats after myocardial infarction (MI) and arteriovenous fistula, respectively. Myocardial infarction was produced by ligation of the left main coronary artery and arteriovenous fistula by direct puncture of the aorta and inferior vena cava below the renal arteries. Pressures and interrenal and glomerular dynamics were obtained using classic micropuncture techniques. Both forms of cardiac failure were characterized by elevated left ventricular end-diastolic pressure (LVEDP), reduced mean arterial pressure, and increased cardiac mass. Left ventricular end diastolic pressure was higher in MI rats, and effective renal plasma flow (ERPF) tended to be reduced in both forms of cardiac failure. There were no apparent differences in effective renal plasma flow between two models. In addition, single-nephron plasma flow and single-nephron glomerular filtration rate were reduced, and single-nephron filtration fraction and glomerular capillary pressure (PG) were increased in both models. These changes were associated with higher afferent and efferent arteriolar resistances and lower ultrafiltration coefficients. Despite these similarities, PG was higher in MI rats, yet LVEDP correlated directly with PG (r = 0.73; P < 0.001) and efferent arteriolar resistances (r = 0.72; P < 0.01). Therefore, although systemic arterial pressure and effective renal plasma flow were similar in both models of cardiac failure, PG was significantly higher in MI rats with higher LVEDP than in arteriovenous fistula rats.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7985721 TI - Treatment of aplastic anemia with an investigational antilymphocyte serum prepared in rabbits. AB - The authors evaluated antilymphocyte serum prepared in rabbits (ALS-R) as an alternative to antilymphocyte serum prepared in horses (ALG-H) in the therapy of aplastic anemia. Between 1980 and 1993, 57 evaluable patients received ALS-R and prednisone +/- cyclosporine +/- androgens. Standard response criteria were used and patients were evaluated at 3 months from the start of therapy. Median age was 43 years. Disease was present for up to 2 months in 24 patients, 2-5 months in 14 patients, and 6 months or more in 19 patients. Disease was severe in 30 patients and moderate in 27. Responses occurred in 16 (28%) of 57 patients. Responses were more frequent in females, in patients treated within 6 months of diagnosis, and in patients with severe disease. Among patients receiving ALS-R and cyclosporine within 2 months of diagnosis, 46% responded. After ALS-R therapy, 20 patients received ALG-H; 8 (40%) of 20 responded. Eight patients receiving ALS-R previously had received ALG-H; 2 (25%) of these 8 patients responded. Toxicity of ALS-R was minimal. Antilymphocyte serum prepared in rabbits, in conjunction with other immunosuppressive agents, represents an effective alternative to ALG-H in aplastic anemia, especially in patients previously treated with ALG-H. PMID- 7985722 TI - Thyrotoxicosis-induced congestive heart failure in an urban hospital. AB - Thyrotoxicosis has been associated with several cardiac complications, including atrial fibrillation (AF), functional cardiomyopathy, and congestive heart failure (CHF). Thyrotoxicosis-induced CHF has been considered an unusual complication of thyrotoxicosis, occurring generally in older patients. To determine the nature and frequency of this complication of thyrotoxicosis in an adult, hospitalized population, the authors consecutively evaluated all admissions to a 535-bed urban hospital during a 14-month period. Admitted during the study period were 177 individuals with a principal diagnosis of AF and 21 individuals with a principal diagnosis of thyrotoxicosis. Eleven of these individuals had concomitant AF and thyrotoxicosis, which was 6% of the AF group. Of these 11 patients, 5 had clinically apparent CHF without evidence of other organic heart disease (Group A) and 6 had only AF without clinical CHF (Group B). The 5 patients with CHF had a significantly lower mean age (36) than the 6 with thyrotoxicosis and AF only (P < 0.03). Echocardiography revealed Group A to have a mean of 2.8 cardiac chambers enlarged compared with a mean of 1 in Group B (P < 0.008). Four of the five patients with CHF had normal left ventricular function. Mean levels of serum thyroxine, albumin, hematocrit, left ventricular percent shortening, and left atrial diameter were similar in groups A and B. Based on the authors' data, thyrotoxicosis-induced CHF is not as rare a complication of thyrotoxicosis in young individuals as reported previously. Thyrotoxicosis-induced CHF most commonly has a dilated cardiomyopathy and high output failure. PMID- 7985723 TI - Can you hold please? How internal medicine residents deal with patient telephone calls. Telephone Encounters Learning Initiative Group. AB - Little is known about the mechanisms used in internal medicine residency programs to handle patient telephone calls. To address this, a survey of internal medicine residents was conducted at 10 different internal medicine residency programs. The response rate was 76% (N = 388). Approximately 90% of the residents handled patient telephone calls. The residents saw a mean of 7 patients per week in clinic (standard deviation +/- 2) and received an average of 2 patient calls daily (standard deviation +/- 2). The mean number of patient calls received each night on-call was 3 (standard deviation +/- 6) and on weekend call days, an average of 4 patient calls were received (standard deviation +/- 8). Internal medicine residents reported spending an average of 7 minutes per call talking to the patient (standard deviation +/- 5) and 8 minutes in follow-up activities (standard deviation +/- 6). Residents reported documenting calls less than 35% of the time. Residents disagreed with the statements "I am very satisfied with my patient telephone call system" and "My patients are very satisfied with my telephone call system." Most internal medicine residents handle a significant amount of patient telephone calls, and the systems for handling these calls are less than satisfactory. The procedures used to manage patient calls and the training for this component of practice should be improved. PMID- 7985724 TI - Internal medicine preceptorships: three successful programs. AB - Undergraduate medical education is evolving to include community physicians in the training of students in the outpatient setting. The task of designing and implementing such preceptorships can be hindered by financial, institutional, and logistic factors. Nonetheless, several institutions have successfully begun such preceptorships, even in the absence of major federal or philanthropic funding. In this article, three institutions offer suggestions for overcoming the factors hindering the development of a successful preceptorship. PMID- 7985725 TI - Clinical validation of the Welch-Allyn Pneumocheck hand held spirometer. AB - Pulmonary function is predictive of morbidity and mortality. Therefore, in epidemiologic studies, researchers seek to measure pulmonary function with portable spirometers feasible for use in clinics or participants' homes. The purpose of this study was to validate a hand held spirometer, the Welch-Allyn Pneumocheck, against standard pulmonary function tests. The authors used a convenience sample of 66 subjects. All subjects were asked to perform three vital capacity maneuvers with the Welch-Allyn Pneumocheck and then either a water seal spirometer or heated pneumotach in a hospital pulmonary function laboratory. The mean forced vital capacity (FVC) obtained with the Pneumocheck was 3.50 liters (standard deviation (SD) = 1.28) compared with 3.31 liters (SD = 1.24) for the pulmonary function laboratory. The correlation between the two measures was 0.98; the mean difference was 0.19 L (95% confidence interval = 0.12 to 0.26). The mean forced expiratory volume at one second (FEV1) was 2.31 L (SD = 1.07) for the Pneumocheck compared with 2.32 L (SD = 1.06) for the pulmonary function laboratory values. The correlation between the two measures was 0.99; the mean difference was 0.01 L (95% confidence interval = -0.03 to 0.04). Of the 46 subjects originally classified by the Pneumocheck as having FEV1/FVC ratios of less than 0.75, 10 (22%) had ratios greater than or equal to 0.75 after correcting for the FVC difference between methods. Therefore, there was an excellent correlation between the Welch-Allyn Pneumocheck and pulmonary function laboratory values for FVC and FEV1. Small systematic differences in FVC measures can lead to substantial misclassification rates when evaluating FEV1/FVC ratios. PMID- 7985726 TI - The role of the hematologist/oncologist as a primary care provider. AB - To determine the role of the hematologist-oncologist as a primary care provider, a survey was administered to a consecutive sample of 238 hematology-oncology patients. Patients were selected at random from the outpatient hematology oncology clinics at three institutions: 66.1% from a university medical center, 22.5% from a private hospital, and 11.4% from a health maintenance organization affiliated clinic. A total of 73 (30.9%) respondents reported they would see their hematologist-oncologist (heme/onc) for routine illnesses, such as sinus or bladder infections. Of the respondents who did not have a family doctor, the percentage increased to 45.5%. Of those patients who had other medical problems, such as hypertension or diabetes, 46 (43.0%) were followed by their heme/onc for these other medical problems. If the respondent did not have a family doctor, the percentage increased to 66.0%. Patients at the university medical center more frequently did not have a family doctor and used their heme/onc for primary care to a greater degree than patients at the private hospital and health maintenance organization (HMO)-affiliated clinic. A total of 55.9% of the respondents reported having the best physician-patient relationship with their heme/onc, whereas only 8.5% had the best relationship with their family doctor. The heme/onc does provide primary care for their patients. If the patient does not have a family doctor, the amount of primary care administered by the heme/onc greatly increases. It is likely that patients rely on their heme/onc for this care because of the close physician-patient relationship that develops as a result of the frequent clinic visits required by many patients with cancer or blood disorders. PMID- 7985728 TI - Management of acromegaly: a review. PMID- 7985727 TI - Identification and activity of cytosol creatine phosphokinase enzymes in normal and diseased skin. AB - Phosphocreatine molecules (PCR) in skin regenerate adenosine triphosphate and help cutaneous tissue survive ischemia associated with skin flaps, grafts, and hair transplantation procedures. In addition, PCR concentration in psoriasis is elevated many times above normal, indicating either overproduction of PCR by mitochondrial creatine phosphokinase (CPK) enzymes or a defect in cytosol CPK enzymatic activity. Skin CPK isoenzymes, before this study, have not been identified. Herein, for the first time, cytosol CPK enzymatic activity was measured in normal and psoriatic, involved and uninvolved skin, skin tumors, and mouse skin and keratinocyte cell cultures. Creatine phosphokinase MM is the major isoenzyme in normal, uninvolved psoriatic and mouse skin. Total CPK enzymatic activity was increased in psoriasis and skin tumors. These data clearly indicate that increased PCR concentration in a psoriatic skin is not a result of decreased cytosol CPK enzymatic activity. PMID- 7985729 TI - Can computers stop errors? PMID- 7985730 TI - Critical incidents. PMID- 7985731 TI - Recognizing depression in elderly patients. PMID- 7985732 TI - Atrial fibrillation. PMID- 7985733 TI - How to protect your patient from DVT. PMID- 7985734 TI - The nursing life. 'I know I hurt, Gram'. PMID- 7985735 TI - The power of hope. PMID- 7985736 TI - Ruptured Achilles tendon. PMID- 7985737 TI - Stavudine (Zerit). New antiretroviral joins arsenal against HIV. PMID- 7985738 TI - A child too bright. PMID- 7985739 TI - Cruising the 'information superhighway'. PMID- 7985740 TI - Entrepreneurship: a global movement. PMID- 7985741 TI - Feliz Navidad. PMID- 7985743 TI - Predicting outcome in malaria: correlation between rate of exposure to infected mosquitoes and level of Plasmodium falciparum parasitemia. AB - The level of Plasmodium falciparum parasitemia at clinical presentation has repeatedly been shown to correlate with severity of disease. Using data collected in western Kenya over 21 months, we examined associations between exposure variables, especially exposure to infective mosquitoes, and prevalence and density of P. falciparum parasitemia among 1,007 children six months to six years of age. The prevalence of P falciparum infection was similar at all exposure levels, but there was a correlation between exposure to sporozoite-infected mosquitoes over the previous 28-day period, and geometric mean parasite density of each cohort (Spearman rank coefficient = 0.724, P = 0.002). The relative odds of having a parasite density > or = 5,000/microliters was increased almost two fold among individuals exposed to more than 10 infective bites during the prior 28-day period. Children enrolled during the highest incidence period were 80% more likely to have a density > or = 5,000/microliters relative to individuals enrolled during periods of lower incidence. The data suggest that measures, such as malaria vaccines, that reduce parasite densities by limiting numbers of sporozoites reaching the liver, or merozoites released from the liver, will reduce malaria-associated morbidity and mortality, even when they do not prevent all infections. PMID- 7985742 TI - The efficacy of antimalarial regimens containing sulfadoxine-pyrimethamine and/or chloroquine in preventing peripheral and placental Plasmodium falciparum infection among pregnant women in Malawi. AB - To define an effective and deliverable antimalarial regimen for use during pregnancy, pregnant women at highest risk of malaria (those in their first or second pregnancy) in an area of Malawi with high transmission of chloroquine (CQ) resistant Plasmodium falciparum were placed on CQ and/or sulfadoxine pyrimethamine (SP). Of 38 pregnant women who received CQ treatment followed by weekly CQ prophylaxis (CQ/CQ) for at least 45 days prior to delivery, 32% had placental malaria infection, compared with 26% of 50 pregnant women who received a treatment dose of SP followed by weekly CQ prophylaxis (SP/CQ), and only 9% of 71 pregnant women who received a two-dose SP regimen (SP/SP; given once during the second trimester and repeated at the beginning of the third trimester) (P = 0.006, by chi-square test). During the peak transmission season from April to July, 47% of the women who received CQ/CQ had placental malaria infection at delivery, as compared with 37% of the women who received SP/CQ, and 10% of women who received SP/SP (P = 0.004, by chi-square test). Among women in their first or second pregnancy, two treatment doses of SP were highly effective in decreasing the proportion of women with placental malaria infection at delivery. PMID- 7985744 TI - Leishmania (Viannia) lainsoni: first isolation in Peru. AB - Surveys were conducted from 1986 through 1992 to define the etiology and geographic distribution of human leishmaniasis in Peru. Lesion aspirates and skin biopsies were obtained from clinically diagnosed cases of leishmaniasis and tested for promastigotes by standard culture techniques. The isozyme profile of the isolates was determined by the cellulose acetate electrophoresis technique. Data indicated that the isozyme profiles for Leishmania isolates from six patients were similar to that of reference strains of L. lainsoni. These results are the first reported evidence of L. lainsoni and the first association of this parasite with human cases of cutaneous leishmaniasis in Peru. PMID- 7985745 TI - Predicting Ixodes scapularis abundance on white-tailed deer using geographic information systems. AB - We collected 1,410 Ixodes scapularis from 139 white-tailed deer in Kent County, Maryland during the 1990 hunting season. A geographic information system was used to extract 41 environmental variables in the areas surrounding the collection sites of the deer. Stepwise linear regression was used to evaluate the association between the abundance of ticks on deer and the environmental data. A significant statistical association was observed between the abundance of I. scapularis and seven environmental variables (R = 0.69). Tick abundance was negatively correlated with urban land use patterns, wetlands, the amount of privately owned land, soils that tended to be saturated with water, and one drainage system. Tick abundance was positively correlated with well-drained, sandy soils having low water tables. These results indicate that geographically referenced environmental data may be useful in anticipating the risk of exposure to vectors over large areas. PMID- 7985746 TI - The first epidemic of dengue hemorrhagic fever in French Guiana. AB - From July 1991 to October 1992, an outbreak of dengue spread into the main urban areas of French Guiana, where 90% of the country's 114,808 inhabitants live. In mid-July 1991 dengue-2 virus was identified as being responsible for most cases, while dengue-1 virus was rarely isolated and circulated at a low level. The number of dengue cases during this period was unknown because there was no clinically based dengue surveillance system. The only available data were for the number of suspected cases as indicated by the number of patients for whom blood samples were submitted to a laboratory for dengue diagnosis. Eight hundred forty seven of the 2,948 suspected cases were diagnosed in the laboratory as dengue cases. Six fatal cases were reported. This outbreak was marked by the appearance of the first clinical cases of dengue hemorrhagic fever (DHF) in French Guiana. Forty cases met the World Health Organization definition of clinical DHF: 32 were grade II, seven were grade III, and one was grade IV and fatal. Eighteen cases were confirmed in the laboratory and 12 were probable; there was no proof of the dengue etiology for the remaining patients. PMID- 7985747 TI - Prevalence of infection with Junin virus in rodent populations in the epidemic area of Argentine hemorrhagic fever. AB - We report the results of indirect fluorescent antibody screening for antibody to Junin virus in 1,101 sera from small mammals captured on two mark-recapture grids in the epidemic area of Argentine hemorrhagic fever. Twenty-six of 29 seropositive animals were the cricetid rodent Calomys musculinus, for a 30-month prevalence of 7.9% in that species. Combining these data with previously published data on antigen detection provided an estimated total prevalence of infection of 10.9% for this, the principal reservoir species. Other infected species included two cricetids, C. laucha and Bolomys obscurus, and a predatory carnivore, Galictis cuja. Approximately half of infected animals simultaneously carried serum antibody and antigen in blood and saliva, some for 29-61 days. Except for C. laucha, which was associated with crop habitats, seropositive animals were strongly associated with the relatively rare roadside and fence-line habitats. Seropositive C. musculinus were predominantly males in the oldest age and heaviest body mass classes, and seropositive males were twice as likely to have body scars as seronegative males. These observations suggest that most infections were acquired through horizontal transmission and that aggressive encounters among adult, male C. musculinus in relatively densely populated roadside and fence-line habitats are an important mechanism of transmission of Junin virus within reservoir populations. PMID- 7985748 TI - Evidence of natural bluetongue virus infection among African carnivores. AB - Bluetongue is an International Office of Epizootics List A disease described as the century's most economically devastating affliction of sheep. Bluetongue (BLU) viruses were thought to infect only ruminants, shrews, and some rodents, but recently, inadvertent administration of BLU virus-contaminated vaccine resulted in mortality and abortion among domestic dogs. We present evidence of natural BLU virus infection among African carnivores that dramatically widens the spectrum of susceptible hosts. We hypothesize that such infection occurred after ingestion of meat and organs from BLU virus-infected prey species. The effect of BLU virus on endangered carnivores such as the cheetah and African wild dog requires urgent investigation. Also, the role of carnivores in the epizootiology of this disease needs elucidation. PMID- 7985749 TI - Respiratory syncytial virus infection in hospitalized patients and healthy children in El Salvador. AB - Nasopharyngeal specimens from 42 children less than one-year old hospitalized with bronchiolitis or pneumonia in El Salvador were analyzed for the presence of subgroup-specific respiratory syncytial virus (RSV) antigens by the indirect immunofluorescence technique. The antigen RSV-A was demonstrated in 28 children, RSV-B in three, and in one child subgroup, specificity could not be determined. The male:female ratio in the RSV-infected children was 1.9:1. The most severe disease, requiring intensive care, was observed in two infants with RSV-B infection. Determination of serum IgG, IgA, and IgM antibodies in acute and convalescent sera showed that none of the tests alone had sufficient sensitivity for routine diagnostic purposes, although, in combination, they provided a correct diagnosis in 86% of the RSV-infected children. A seroprevalence study of IgG, IgA, and IgM antibodies in 206 healthy children showed that a primary RSV infection is usually acquired during the first year of life in El Salvador. These results also indicated that reinfections with RSV frequently occur during the first 3-4 years of life and suggest that the occurrence of serum RSV IgA antibodies may be a marker of reinfection. PMID- 7985750 TI - Diarrheal disease in Peru after the introduction of cholera. AB - Surveillance was conducted one day each week from December 1992 through May 1993 to determine the clinical features and etiology of diarrhea among a population in a suburban community of Lima, Peru. Patients who had had three or more loose stools during the previous 24 hr were enrolled at a clinic located in the community or at a nearby regional hospital. A total of 143 cases of diarrhea were detected for an overall rate of 7.1 cases per 1,000 population. The enteropathogens isolated were Vibrio cholerae 01 (31%), enterotoxigenic Escherichia coli (22%), and Salmonella, Shigella, Campylobacter, and Aeromonas species (10%). Specimens from the remaining cases were negative for enteropathogens. All isolates of V. cholerae were susceptible to tetracycline, doxycycline, nalidixic acid, norfloxacin, trimethoprim-sulfamethoxazole, trimethoprim, gentamicin, chloramphenicol, and cephalothin. Cases of diarrhea associated with V. cholerae were more common among adults, and more likely to experience severe dehydration and require hospitalization than the non-cholera cases. Data indicated that among the cases diagnosed, V. cholerae and enterotoxigenic E. coli were the more common causes of diarrhea in a suburban community of Lima during the summer season. PMID- 7985751 TI - Dirofilariasis in Kuwait: first report of human infection due to Dirofilaria repens in the Arabian Gulf. AB - Zoonotic dirofilariasis has been reported sporadically from many areas of the world but thus far, there are no such reports from the Arabian Peninsula. We present the first report of human dirofilariasis from this region in the Middle East and discuss the significance of the finding. A fixed, elongated mass in the abdominal wall of a 50-year-old Kuwaiti man was excised and a worm was identified in an abscess in tissue sections. The location of the nodule in subcutaneous tissue, the diameter of the worm in section, the multilayered cuticle with fine longitudinal ridges on the external layer, prominent internal cuticular ridges, and abundant somatic muscles suggested the diagnosis of the worm as Dirofilaria (Nochetiella) repens, a natural parasite of dogs and cats in Asia, Africa, and Europe. PMID- 7985752 TI - Relationship between humoral response to Plasmodium falciparum merozoite surface antigen-2 and malaria morbidity in a highly endemic area of Papua New Guinea. AB - The prevalence and concentration of antibodies to merozoite surface antigen-2 (MSA-2) were measured in blood samples collected during a cross-sectional survey. Antibodies were measured by enzyme-linked immunosorbent assay using two recombinant proteins that closely approximated the full-length mature MSA-2 polypeptides expressed by the Plasmodium falciparum isolate FC27 and the cloned line 3D7 and that were representative of the dimorphic forms of MSA-2. Antibodies were also measured to a form of the 3D7 MSA-2 lacking the central repetitive sequences (d3D7). High antibody prevalence was observed to all three antigens: the overall prevalence of IgG to FC27, 3D7, and d3D7 was 91%, 90%, and 90%, respectively. The majority of individuals > or = 5 years of age had antibodies to both forms of MSA-2. The geometric mean antibody units increased with age with a plateau being reached by 15-20 years of age. There was a significant positive association of antibody prevalence with both the presence of the parasite and an enlarged spleen in children. This study provides the first evidence that antibodies against nonrepeat regions of MSA-2 are associated with fewer fever episodes and less anemia, both known to be indicators of malaria morbidity. PMID- 7985753 TI - Safety, immunogenicity, and efficacy of a malaria sporozoite vaccine administered with monophosphoryl lipid A, cell wall skeleton of mycobacteria, and squalane as adjuvant. AB - A Plasmodium falciparum circumsporozoite protein (PfCSP) recombinant fusion protein, R32NS1(81), formulated with monophosphoryl lipid A, cell wall skeleton of mycobacteria, and squalane (Detox) was administered to 12 volunteers. One volunteer had malaise and self-limited painful induration at the injection site after the second dose and declined further immunization. The other 11 volunteers tolerated the three doses of 1,230 micrograms of vaccine, but most complained of sore arms; in five cases the pain or malaise was severe enough to interfere with work or sleep. Two weeks after the third dose of vaccine, four of the 11 immunized volunteers had > or = 14 micrograms/ml of antibodies to the repeat region of the PfCSP in their serum. Two of these four volunteers did not develop P. falciparum parasitemia when challenged by the bite of five mosquitoes carrying P. falciparum sporozoites. The seven volunteers with lower levels of antibodies and 11 of 11 controls developed parasitemia. These data are consistent with other studies, and indicate that vaccine-induced antibodies against the repeat region of PfCSP can prevent effective sporozoite infection of hepatocytes in humans. The challenge is to improve the immunogenicity of PfCSP-based vaccines, and to develop methods for including PfCSP peptides as components of multitarget malaria vaccines. PMID- 7985754 TI - Acridine orange diagnosis of Plasmodium falciparum: evaluation after experimental infection. AB - The value and role of the acridine orange/microhematocrit tube method (quantitative buffy coat [QBC] analysis) in the diagnosis of malaria remains controversial. To establish the true sensitivity of this test in comparison with the thick blood film, we studied 49 subjects who were experimentally infected with Plasmodium falciparum in 10 malaria vaccine and infectivity trials. Diagnosis was made by the acridine orange staining method 1-3 days earlier than by the thick blood film in 23 subjects (47%) and at the same time as the thick blood film in 20. On the other hand, diagnosis was made by thick blood film earlier than by the acridine orange staining method in six individuals. There were no false positive results using acridine orange among 584 specimens studied. Diagnosis was made using acridine orange at a parasitemia of less than 11 parasites/microliters of blood in 65% of cases. Where available, the acridine orange assay is clearly preferable in terms of speed and accuracy to the thick blood film for diagnosis with parasitemias of less than 150/microliters of blood, and perhaps as important, for ruling out infection with P. falciparum in a symptomatic patient. PMID- 7985755 TI - Detection of Plasmodium falciparum in human blood by a nested polymerase chain reaction. AB - We have developed a simple method for direct detection of Plasmodium falciparum parasites in infected human blood using a nested polymerase chain reaction. Whole blood (10 microliters) was obtained by finger puncture and suspended in a microcentrifuge tube containing phosphate-buffered saline. For removal of components that might inhibit the PCR, blood samples were treated with saponin and washed by centrifugation. After three cycles of a two-step incubation (3 min at 94 degrees C and 3 min at 55 degrees C), the first amplification was done with oligonucleotide primers specific for the junction region of the gene coding for the dihydrofolate reductase-thymidylate synthase in P. falciparum. A 1-microliter portion of the first amplification was then amplified again with a second set of primers, and 226-basepair fragments were generated. The amplified products were analyzed by agarose gel electrophoresis with ethidium bromide staining. Experiments with cultured parasites showed that the method could detect as few as 13 parasites in 10 microliters of whole blood. In 1991, 101 samples from 98 donors were collected in Guadalcanal, Solomon Islands. Eight of these samples gave positive results by both examination of thin blood smears and by the nested PCR. There was a correlation between parasite densities and the intensity of the results by the nested PCR. The method is suitable for detection of asymptomatic parasite carriers and evaluation of medical treatment on clinical cases. PMID- 7985756 TI - Impact of repeated community-based selective chemotherapy on morbidity due to schistosomiasis mansoni. AB - The impact of repeated chemotherapy on morbidity due to schistosomiasis mansoni was evaluated in Gihungwe (initial prevalence 58%) and Buhandagaza/Kizina (33%), two village clusters in Burundi. Surveys were carried out with reference to the first treatment (month 0) at months -6, -3, 0, 3, 6, 9, 12, 24, and 36. Praziquantel (40 mg/kg) was given at months 0, 12, 24, and 36 to those showing eggs in the feces with a single 28-mg Kato slide. At each survey, duplicate Kato smears were examined, and all participants responded to a standardized medical history interview and underwent a clinical examination. In the three preintervention surveys, spleen and liver rates remained stable at the community and the individual level. The frequencies of diarrhea and abdominal pain varied to some extent, but they were consistently higher in the most heavily infected villages and age groups and remained relatively stable at the individual level. At the final survey, the prevalence of infection had decreased to 25%, and the frequency of diarrhea from 19-26% to 10% in both village clusters. This impact was strongest in the younger age groups. The frequency of abdominal pain was reduced only at the short term and in selected age groups. Organomegaly decreased only to a limited extent in those treated, and increased in those not treated, possibly due to the impact of malaria. The net result was that no measurable impact of the treatments on organomegaly at the community level could be demonstrated. In the light of these results, the relevance of community-based chemotherapy in moderate foci is questioned. PMID- 7985757 TI - Vascular clogging, mononuclear cell margination, and enhanced vascular permeability in the pathogenesis of human cerebral malaria. AB - To document histopathologic evidence on the pathogenic mechanism of human cerebral malaria, we used light microscopy to study brain specimens from 23 patients who died of central nervous system involvement with Plasmodium falciparum. Sequestration of parasitized red blood cells (PRBCs) leading to cerebral capillary clogging was seen. In a few specimens, vascular clogging by PRBCs was associated with margination of mononuclear cells. In others, capillaries were virtually empty and lymphocytes and monocytes were seen in apposition (marginated) to the capillary endothelial surface. The endothelial cells appeared plump, hypertrophied, and prominent. The capillary wall appeared thickened by fibrinous material. Massive intercellular brain edema along with extravasated red blood cells, mononuclear cells, and plasmatic fluid was also noticed. In addition to hypoxia induced by PRBC-mediated vascular clogging, marginating mononuclear cells may contribute to the pathogenesis of cerebral malaria. The precise role played by this phenomenon needs further evaluation. PMID- 7985758 TI - A strong association between mefloquine and halofantrine resistance and amplification, overexpression, and mutation in the P-glycoprotein gene homolog (pfmdr) of Plasmodium falciparum in vitro. AB - Stepwise selection for increased mefloquine resistance in a line of Plasmodium falciparum in vitro resulted in increased resistance to halofantrine and quinine, increased sensitivity to chloroquine, and amplification and overexpression of the P-glycoprotein gene homolog (pfmdr1). A point mutation (tyrosine to phenylalanine) noted at amino acid 86 in pfmdr1 in the mefloquine-resistant line W2mef was amplified in more resistant lines derived from it by in vitro selection pressure with mefloquine. Conversely, lines selected for increased chloroquine resistance exhibited a revertant phenotype that was sensitive to mefloquine and halofantrine. These lines also demonstrated increased sensitivity to quinine, loss of amplification of pfmdr1, loss of the mefloquine/halofantrine phenylalanine-86 mutation, and selection for a tyrosine-86 mutation previously associated with chloroquine resistance. These findings provide strong evidence for pfmdr1 mediating cross-resistance to halofantrine and mefloquine in P. falciparum in vitro. PMID- 7985759 TI - Allelic variation in the circumsporozoite protein of Plasmodium falciparum from Thai field isolates. AB - Allelic variation in the Plasmodium falciparum circumsporozoite (CS) protein gene has been examined by sequencing the entire gene in 15 isolates from an endemic area of Thailand. The isolates contain a total of six new allelic forms of the tetrapeptide repeats and eight variants of the T cell epitope (TCE) region of the CS gene. All nucleotide substitutions in the TCE are nonsynonymous. There is no apparent association between the sequence patterns in the repeats and in the TCE. Comparison of the TCE with published sequences has shown that most variants of our isolates are not identical to those found in different geographic areas, suggesting geographic variation in genetic diversity of the CS protein. In a phylogenetic tree, the new Thai alleles did not cluster together, suggesting a considerable heterogeneity within some geographic areas. Furthermore, analyses of tetrapeptide repeats from a number of isolates and strains showed evidence of three genetic mechanisms for the generation of variation in the repeats of the CS gene: point mutation, duplication of one or more repeat units, and intragenic recombination. PMID- 7985760 TI - Coexistence of two species of Leishmania in the digestive tract of the vector Lutzomyia ovallesi. AB - Leishmania isolated from the digestive tract of a naturally infected Lutzomyia ovallesi sand fly were cultured in blood agar for rapid growth, cloning, and subsequent identification through schizodeme analysis, dot-blot hybridization, use of monoclonal antibodies with various specificities and absorbed polyclonal antibodies. Twenty-three clones isolated from the primary culture were identified. The results showed that parasites belonging to some clones corresponded to the L. mexicana complex, while others belonged to the L. braziliensis complex. These results clearly establish the coexistence of two Leishmania species in the digestive tract of a single Lu. ovallesi sand fly. PMID- 7985761 TI - DNA probe-based classification of Simulium damnosum s. l.-borne and human-derived filarial parasites in the onchocerciasis control program area. AB - The development of polymerase chain reaction-based methods using strain- and species-specific DNA probes for Onchocerca volvulus has permitted classification of individual parasites from every stage of the parasite's life cycle. This technology has been applied on a large scale basis by Onchocerciasis Control Program (OCP) in West Africa. The primary objective of the OCP in using the DNA probes was to obtain accurate estimates of the annual transmission potential of the blinding strain of O. volvulus. The DNA probe classification of larvae collected throughout the OCP area demonstrated that larvae of less pathogenic strains of O. volvulus and other filarial parasites carried by Simulium damnosum s.l. have resulted in a significant overestimation of the annual transmission potential for blinding onchocerciasis. This effect is particularly pronounced along the southern border of the OCP, where the blinding and less pathogenic strains of O. volvulus coexist, and in the north of the control area, where animal parasites, particularly O. ochengi, may even predominate. A second objective of the OCP in applying the DNA probe technology was to determine the distribution of blinding and less pathogenic O. volvulus in infected individuals along the southern border of the control area. Results obtained from these studies have generally confirmed the distribution pattern established by previous epidemiologic studies. In addition, DNA probe classifications have demonstrated that in areas where the blinding and less pathogenic strains of O. volvulus coexist, a single individual may simultaneously be infected with both strains of the parasite. PMID- 7985762 TI - Identification of genes that encode Fasciola-specific arc 2 antigens. AB - Previous studies have shown that serum from humans with fascioliasis had precipitating antibodies that identified a line of precipitation as specific for Fasciola. This Fasciola-specific band was designated arc 2. The specificity of a Fasciola-specific anti-arc 2 antiserum, evaluated by Western blot analysis, reveals a mosaic of antigens with molecular weights in the range of 10-43 kD. In the current study, the antibodies reacting with a subset of antigens in the 10-21 kD range were eluted from nitrocellulose and used to probe an F. hepatica cDNA library. Four clones were purified and amplified by the polymerase chain reaction. The DNA hybridizations among these clones revealed different groups of clones derived from different mRNAs. The finding of multiple genes supports the observation that F. hepatica arc 2 is a mosaic of antigens. The studies show that molecular cloning technology can be used to identify potential genes, each of which encode distinct antigens that may be used for the specific immunodiagnosis of fascioliasis. PMID- 7985763 TI - Differential modulation of murine cellular immune responses by salivary gland extract of Aedes aegypti. AB - The ability of salivary gland extract (SGE) of Aedes aegypti to modulate cellular immune responses was investigated in a mouse model. Cytokine production was induced in naive and antigen-primed murine (BALB/c) spleen cells in vitro by stimulation with the T cell mitogen concanavalin A or the T cell-dependent antigen ovalbumin (OVA), respectively. Inclusion of Ae. aegypti SGE in in vitro culture with naive cells caused significant suppression of the cytokines interleukin-2 (IL-2) and interferon gamma in culture supernatants, while levels of other cytokines (IL-4 and IL-5) were unaffected by SGE. In contrast, SGE did not affect cytokine production by antigen-activated cells derived from OVA-primed mice. To determine whether SGE could inhibit the responsiveness of cells to exogenous cytokine stimuli, optimized quantities of lymphocyte growth factor cytokines IL-2 and IL-4 were added to SGE-treated spleen cells and the degree of cellular proliferation was determined. Cellular proliferation in response to IL-2 was markedly suppressed by prior exposure of cells to SGE, while the proliferative response to IL-4 was also affected by SGE but to a lesser extent. These results confirm that mosquito SGE can modulate host immune responses, and suggest that in Ae. aegypti modulation is directed primarily against cytokines associated with type 1 lymphocyte responses. The mode of immunomodulation and the possible relevance of these results to vector-borne disease research are discussed. PMID- 7985764 TI - Astrakhan fever rickettsiae: antigenic and genotypic analysis of isolates obtained from human and Rhipicephalus pumilio ticks. AB - Two spotted fever group rickettsia strains, A-108 and A-167, were isolated from the hemolymph of Rhipicephalus pumilio ticks collected in the Astrakhan region of Russia, which is area endemic for Astrakhan fever. These tick isolates were compared with a strain isolated from a patient suffering from Astrakhan fever and with reference spotted fever group rickettsiae strains. New tick isolates and the human strain were identical in their serologic, antigenic, and genetic characteristics by several methods: microimmunofluorescence, protein gel electrophoresis with immunoblotting, polymerase chain reaction followed by restriction endonuclease fragment length polymorphism analysis, and pulsed-field gel electrophoresis (PFGE). Astrakhan fever rickettsiae were found to be serologically and antigenically similar to Israeli spotted fever rickettsiae. Both of them probably belong to a single Rickettsia conorii pathotype complex. Only PFGE pattern analysis could clearly discriminate Astrakhan fever rickettsiae from other isolates. PMID- 7985765 TI - Annual directory of international opportunities. PMID- 7985766 TI - [Spontaneous abortion]. PMID- 7985767 TI - [Intrauterine bacterial and viral infections of the fetus and newborn]. PMID- 7985768 TI - [Perinatal pathology in newborns]. PMID- 7985769 TI - [50 years to the Scientific Center of Obstetrics, Gynecology and Perinatology of the Russian Academy of Medical Sciences]. PMID- 7985770 TI - [Antenatal diagnosis of the fetus]. PMID- 7985771 TI - [Medical and social aspects of maternal and newborn health]. PMID- 7985772 TI - [Development of experimental and theoretical research in obstetrics]. PMID- 7985773 TI - [Age-specific pathology in female reproductive system]. PMID- 7985774 TI - [Reconstructive surgery in gynecology]. PMID- 7985775 TI - [Infertile marriage]. PMID- 7985776 TI - [Contraception in the family planning]. PMID- 7985777 TI - [Development of alternative method, extracorporeal fertilization and embryo transfer, for the treatment of infertility]. PMID- 7985778 TI - [High risk pregnancy and labor]. PMID- 7985779 TI - From electrophoretically separated protein to identification: strategies for sequence and mass analysis. PMID- 7985780 TI - Deoxyhypusine synthase assay based on the use of polyhistidine-tagged substrate and metal chelate-affinity chromatography. AB - Hypusine formation on the eukaryotic initiation factor 5A (eIF-5A) precursor is a unique spermidine-dependent post-translational modification that appears to be ubiquitous in eukaryotic cells. In this modification, a specific lysine residue of eIF-5A precursor protein is first converted to deoxyhypusine by an addition of a butylamino group derived from spermidine; the deoxyhypusine residue is then hydroxylated to form hypusine. Deoxyhypusine synthase, an NAD(+)-dependent enzyme, catalyzes the first step of hypusine formation on the eIF-5A precursor. Since deoxyhypusine formation represents one of the most specific polyamine dependent reactions in eukaryotic cells, the reaction may play an important role in cellular growth regulation. To facilitate the study of the function and significance of deoxyhypusine formation, we have developed a rapid and sensitive assay for deoxyhypusine synthase. The assay relied on the use of hexahistidine tagged recombinant Neurospora 21-kDa eIF-5A precursor protein as the substrate protein. The radiolabeled polyhistidine-tagged protein, once modified by [3H]spermidine, was separated from free [3H]spermidine by a microscale metal affinity chromatography in a dot blot filtration apparatus and quantified by liquid scintillation counting. The assay procedure is quick and simple compared to other methods reported in the literature. The sensitivity is limited by the specific activity of [3H]-spermidine in the reaction mixture. The metal-affinity chromatographic assay for deoxyhypusine synthase should facilitate the purification, characterization, and functional studies of this enzyme. PMID- 7985781 TI - Simultaneous quantitation of endogenous levels of cortisone and cortisol in human nasal and bronchoalveolar lavage fluids and plasma via gas chromatography negative ion chemical ionization mass spectrometry. AB - Investigation of the influence of pulmonary disease upon local catabolism of cortisol in vivo is limited by the lack of availability of a selective and sensitive assay for simultaneous quantitation of cortisol and cortisone in lung and nasal lavage fluids as well as in plasma. Synthesis of bispentafluorobenzylcarboxymethoxime derivatives of cortisone and cortisol followed by trimethylsilylation yields compounds with almost ideal gas chromatographic properties. The derivatized steroids generate intense M(-.)-181 fragment ions in negative ion chemical ionization mass spectrometry. Monitoring of ions at m/z 829 and m/z 903, respectively, for cortisone and cortisol and corresponding fragment ions generated from multideuterated internal standards provides the analytical basis for assessment of local in vivo conversion of cortisol to cortisone in the respiratory system of human subjects. The assay method displays excellent reproducibility with variations < or = 10%. Detection limits are < or = 1 pg of steroid analyte per injection (S/N > 3). Endogenous levels of cortisone and cortisol, respectively, measured in human samples were as follows: nasal lavage fluid, 47 and 25 pg/ml; bronchoalveolar lavage fluid, 380 and 153 pg/ml; plasma 12.8 and 61.6 ng/ml. PMID- 7985782 TI - A protein/peptide assay using peptide-resin adduct: application to the calmodulin/RS20 complex. AB - To obtain equilibrium and kinetic constants of a protein/peptide complex, we have developed a rapid procedure which uses peptides specifically linked to a resin. With this peptide-resin adduct, bound and free 125I-labeled protein could be easily separated by simple centrifugation. The feasibility of the method was demonstrated with the calmodulin/RS20 complex, where RS20 is the putative calmodulin binding peptide of the smooth muscle myosin light chain kinase (smMLCK). In addition to the wild-type calmodulin (SYNCAM) expressed in Escherichia coli, we also examined calmodulin mutants with charge reversals called SYNCAM12A (DEE 118-120-->KKK) and SYNCAM18A (EEE 82-84-->KKK and DEE 118 120-->KKK). The kinetic analysis of the interaction between SYNCAM and RS20 associated with titration experiments allowed us to measure dissociation constants (KD) in the range of 10(-9) M, in good agreement with previously published data. Moreover, the binding assays showed that SYN-CAM18A did not interact with RS20, whereas SYN-CAM12A did with a KD around 10(-8) M. The lack of binding of SYNCAM18A to RS20 provides an explanation for the lack of smMLCK activation by SYNCAM18A. Altogether, these results demonstrate that peptide-resin can be used as a tool for separating bound from free protein, thus enabling a rapid and reliable quantification of the protein/peptide interaction. PMID- 7985783 TI - Assembly of 18-nucleotide primers by ligation of three hexamers: sequencing of large genomes by primer walking. AB - A novel method (SPEL-6) for sequencing large genomes permits 10-min synthesis of 18-mer primers and their immediate use in DNA sequencing by primer walking. Primers are ligated from three contiguous hexamers complementary to the single stranded or denatured DNA (150:1 ratio), which is used both as the template for ligation and as the DNA to be sequenced. The complete library consists of 4096 hexamers, but sequencing remains very efficient with a fourfold smaller library composed of 1024 degenerate hexamers containing all four nucleotides at their position 3. The SSB protein (which binds to single-stranded DNA) greatly enhances the quality of sequencing ladders. The SPEL-6 method eliminates the need for subcloning, permits direct sequencing of large DNA fragments (of 50 kb or larger), is ideally suited for automation, and should accelerate the sequencing of large genomes by more than one order of magnitude. PMID- 7985784 TI - DNA sequencing with a hexamer string primer and dye-labeled terminators. AB - A method for fluorescence-based DNA sequencing using a hexamer string primer and dye-labeled terminators is described. Sequencing protocols have been determined that provide an average read length of 393 bases with 99.6% base-calling accuracy for single-stranded M13mp18 DNA, and an average read length of 367 bases with 99.4% base-calling accuracy for double-stranded M13mp19 DNA. The signal intensity is stronger than that obtained with a standard 18-mer primer, while the resolution and length of readable sequence are comparable. PMID- 7985785 TI - Real-time competitive kinetic analysis of interactions between low-molecular weight ligands in solution and surface-immobilized receptors. AB - With surface plasmon resonance detection it is possible to measure the binding kinetics between a macromolecule in solution and a receptor immobilized on a sensor surface. The detector response is proportional to the mass of the analyte that binds to the surface, and therefore, a direct observation of a low-molecular weight (lmw) analyte ( < 5000 Da) interacting with its immobilized binding partner is normally not possible. I describe here a competitive approach in which a lmw analyte and a high-molecular-weight analyte react at the same time with the immobilized receptor. Using this approach it is possible to extend kinetic analysis to lmw analyte-receptor interactions. A qualitative analysis allows rapid affinity ranking of different lmw analytes interacting with the same receptor, and a quantitative analysis of binding data allows the calculation of rate constants for the lmw analyte-receptor interaction. The competitive kinetics approach may therefore be used as an alternative to other affinity techniques for the characterization of lmw ligands, for identification of inhibitors, and for drug screening. PMID- 7985786 TI - A continuous fluorometric assay for phospholipases using polymerized mixed liposomes. AB - A versatile continuous fluorometric assay for phospholipases A2, C, and D has been developed utilizing polymerized mixed liposomes made of pyrene-containing phospholipids (5 mol%) uniformly inserted in the polymerized liposomes of 1,2 bis[12-(lipoyloxy)dodecanoyl]-sn-glycero-3-phosphoglycerol (BLPG) and its derivatives. 1-Hexadecanoyl-2-(1-pyrenedecanoyl)-sn-glycero-3-phosphocholine was used for phospholipase A2 and N-(1-pyrenesulfonyl)-egg phosphatidyl ethanolamine for phospholipases C and D. Fluorescence emission of pyrene moieties in polymerized mixed liposomes was strongly quenched by BLPG molecules and, thus, the hydrolysis of pyrene-containing phospholipids and the subsequent displacement of pyrene moieties from the liposomes resulted in a large increase in fluorescence intensity. All the phospholipases tested selectively and rapidly hydrolyzed the inserted pyrene-containing phospholipids, which were readily monitored by measuring an increase in fluorescence emission at 380 nm. Assay conditions for individual phospholipases were optimized by altering interfacial properties of polymerized liposomes, such as surface charge, and subsequently by changing the chemical structure of hydrolyzable phospholipids. Phospholipase activities were linearly proportional to enzyme concentrations in the range from 0.1 to 50 ng. Specific activity determined for phospholipases from a wide variety of sources ranged from 0.5 to 100 mumol/min/mg. Polymerized mixed liposomes are exceptionally stable against chemical and physical degradation and the assay requires only a small amount of pyrene-containing phospholipids. In addition, the polymerized matrix of BLPG (and its derivatives), due to its inertness to the phospholipase hydrolysis, allows the direct measurement of the equilibrium dissociation constant for a protein-liposome complex. PMID- 7985787 TI - Characterization of chain-shortened oxidized glycerophosphocholine lipids using fast atom bombardment and tandem mass spectrometry. AB - Oxidized glycerophosphocholine (GPC) lipids produced by free-radical-initiated lipid peroxidation have been reported to activate human polymorphonuclear leukocytes exerting an effect through the platelet-activating factor receptor, yet few methods have been developed to characterize intact oxidized phospholipids, which may be present in small quantities. In this paper we detail the fast atom bombardment and collision-induced dissociation behavior of 1 hexadecanoyl-2-(5-oxopentanoyl)-GPC and 1-hexadecanoyl-2-pentanedioyl-GPC, two prototypic oxidized glycerophosphocholine lipids produced by hydroxyl radical initiated peroxidation of 1-hexadecanoyl-2-arachidonoyl-GPC. Identities of these two products were established first using EI-GC/MS to analyze the corresponding diglyceride tert-butyldimethylsilyl ether derivatives. The aldehyde moiety of 1 hexadecanoyl-2-(5-oxopentanoyl)-GPC was found to react with FAB amine-containing liquid matrices (e.g., diethanolamine) to form an oxazolidine derivative (87 u increase in mass). No reaction was observed with matrices such as glycerol, thioglycerol, and 3-nitrobenzylalcohol. This derivatization can be used to distinguish an aldehyde-containing oxidized phospholipid from isobaric species not containing an aldehyde moiety. Results also showed that 1-hexadecanoyl-2 pentanedioyl-GPC formed primarily [M-H]- ions rather than the [M-15], [M-60], and [M-86] negative ions expected for GPC lipid species. The ionized omega-carboxyl group of the sn-2 substituent allowed the phosphocholine moiety to remain as a zwitterion. Following collision-induced dissociation, a N-methyl group from the choline was transferred to the omega-carboxyl of the sn-2 substituent prior to generation of the carboxylate anions, which resulted in a 14-u increase in the observed sn-2 carboxylate anion.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7985788 TI - Nucleotide imbalance and polymerase chain reaction: effects on DNA amplification and synthesis of high specific activity radiolabeled DNA probes. AB - Synthesis of radiolabeled DNA probes via polymerase chain reaction (PCR) is a convenient alternative to the more conventional methods of random primer-labeling and nick translation. PCR requires less template and allows the synthesis of radiolabeled probes from specific sequences contained within cloning vectors and genomic DNA. Under nucleotide imbalance conditions where the concentration of the radiolabeled nucleotide was 0.825 microM and the other dNTPs were each > 25 microM, amplification by Taq DNA polymerase was inhibited. Reducing the concentrations of the unlabeled dNTPs resulted in greater yields of amplification product with maximal yield obtained when the concentration of three unlabeled nucleotides was two- to eightfold higher than that of the limiting labeled nucleotide. When we utilized this amplification method for synthesis of an 800-bp glyceraldehyde-3-phosphate (GAPDH) dehydrogenase probe, 87% of the added [32P]dCTP was incorporated into amplification product. Application of this method for synthesis of high specific activity probes ( > 4 x 10(9) cpm/micrograms) up to 2.6 kb in length is demonstrated and utility of the 800-bp GAPDH probe for hybridization to Northern blots for detection of GAPDH mRNA is presented. PMID- 7985789 TI - Batchwise purification of specific tRNAs by a solid-phase DNA probe. AB - A simple and efficient method for purifying a specific tRNA in a single microcentrifuge tube was developed. Oligodeoxyribonucleotides (about 30 mer) with sequences complementary to the 3' side of target tRNAs were synthesized with an aminohexyl linker at the 5' end, immobilized on a silica gel at a high concentration, and used as a solid-phase probe. A mixture of tRNAs was added to a suspension of the solid-phase probe in 2.4 M tetraethylammonium chloride and incubated for 10-30 min. Only a target tRNA hybridized with the immobilized probe at appropriate temperatures and was eluted out by heating. The solid-phase probe showed a large hybridization capacity (up to 17 A260 units/g dry gel) and specific and quantitative recovery of the target tRNA. The intactness of recovered tRNAs was ascertained by both Donis-Keller sequencing and aminoacylation experiments. These features show the usefulness of the solid-phase probe method as a reliable tool for purifying tRNAs whose gene sequences are known. PMID- 7985790 TI - Changes in free calcium in the endoplasmic reticulum of living cells detected using targeted aequorin. AB - The Ca(2+)-activated photoprotein aequorin has been engineered with the endoplasmic reticulum (ER)-targeting sequence from calreticulin at the N-terminus and the KDEL sequence at the C-terminus so that it locates in the ER of living cells. Targeting of apoaequorin to the ER of COS7 cells was demonstrated by immunolocalization. Selective permeabilization of cells expressing the modified protein suggested that targeting was highly efficient. Functional photoprotein was reconstituted in live cells by incubating them with coelenterazine. Light emission from cells expressing ER aequorin showed that the estimated free Ca2+ within the ER of live cells at 37 degrees C was 0.3-1.0 microM, some 10 times that in the cytosol. An increase in the rate constant for aequorin light emission was demonstrated when the cells were warmed from 4 degrees C. This increase could be in part, but not wholly, explained by an increase in rate constants for aequorin at higher temperatures and a change in kinetics as a result of the ER targeting of aequorin. The increase in rate constants in the cells was inhibited by thapsigargin and occurred in the presence or absence of extracellular Ca2+. These results highlight the importance of converting aequorin light emission to rate constants and of calibrating any variants if qualitative and quantitative conclusions are to be drawn about free Ca2+ in intracellular compartments. PMID- 7985791 TI - Separation of glycosaminoglycan-derived oligosaccharides by capillary electrophoresis using reverse polarity. AB - A comparative study on compositional analysis of two sets of eight unsaturated disaccharide standards derived from heparin/heparan sulfate and chondroitin/dermatan sulfate was carried out using capillary electrophoresis performed in both normal and reverse polarity modes. While these heparin/heparan sulfate disaccharides (S. A. Ampofo, H. M. Wang, and R. J. Linhardt (1991) Anal. Biochem. 199, 249-255) and chondroitin/dermatan sulfate disaccharides (A. Al Hakim and R. J. Linhardt (1991) Anal. Biochem. 195, 68-73) have previously been fractionated using normal polarity capillary electrophoresis, multiple buffer systems and conditions were required to separate certain disaccharide isomers and these separations often resulted in poor peak symmetry and significant tailing. This paper demonstrates that reverse polarity capillary electrophoresis completely resolves disaccharide mixtures into all components using a single buffer, 20 mM phosphoric acid-sodium phosphate at pH 3.48. This improved resolution is due primarily to an increase in the sharpness of peaks and improved peak symmetry. Separation of heparin-derived oligosaccharides, ranging from disaccharide to hexasaccharide, had also previously been reported using normal polarity capillary electrophoresis (U.R. Desai, H.M. Wang, S.A. Ampofo, and R.J. Linhardt (1993) Anal. Biochem. 213, 120-127). This paper now demonstrates the separation of 13 heparin-derived oligosaccharides of sizes ranging from disaccharide to tetradecasaccharide using both reverse and normal polarities. An enzymatic digestion of bovine lung heparin containing many of these larger oligosaccharides was also compared in both normal and reverse polarity modes. Mixtures containing oligosaccharides primarily differing in size (number of saccharide units) were better resolved using normal polarity. PMID- 7985792 TI - Determination of 24 variously sulfated galactosaminoglycan- and hyaluronan derived disaccharides by high-performance liquid chromatography. AB - In this report we describe a very sensitive high-performance liquid chromatographic method for the determination of 24 nonsulfated and variously sulfated disaccharides present in chondroitin sulfates, dermatan sulfates, and hyaluronic acid. The method is superior to others in that monosulfated disaccharides at either C-2 or C-3 of the uronic acid moieties and mono-, di-, and trisulfated disaccharides containing N-sulfated galactosamine as well as non , mono-, and oversulfated disaccharides derived from iduronic acid can be determined. Following chondroitinase digestions of tissue extracts or purified hyaluronic acid, chondroitin sulfate, and dermatan sulfate, the non-, di-, and trisulfate delta-disaccharides, are separated by direct injections into HPLC, whereas the monosulfated delta-disaccharides are chromatographed after a simple reduction of the galactosamine carbonyl group with sodium borohydride. The various sulfated delta-disaccharides are separated on an amino column (Econosphere NH2) and recorded at 231 nm. The column is eluted isocratically with 5 mM sodium dihydrogen orthophosphate, pH 2.55, for nonsulfated delta disaccharides; 50 mM sodium dihydrogen orthophosphate, pH 2.50, for reduced monosulfated; and 50 mM sodium sulfate-10 mM sodium acetate, pH 5.0, for the separation of di- and trisulfated delta-disaccharides. A linear detector response was obtained for injections up to 50 micrograms of delta-disaccharides. As little as 5-8 ng of nonsulfated, 8-11 ng of monosulfated, 12-15 ng of disulfated, and 25 30 ng of trisulfated delta-disaccharides can be reliably detected. Application of this HPLC method to the analysis of various glycosaminoglycans in conjunction with chondroitinase AC, ABC, or B digestions and sulfatase hydrolysis adds to the knowledge of the structural spectrum of the galactosaminoglycans. It was thus possible to identify 24 different disaccharides in chondroitinase-susceptible glycosaminoglycans, including all C-5 epimeric disaccharides and those sulfated at C-2 or C-3 of the uronic acids and at the amino group of the galactosamine. PMID- 7985793 TI - Direct detection of pullulanase activity in electrophoretic polyacrylamide gels. PMID- 7985794 TI - Fluorometric nuclear run-on assay with oligonucleotide probe immobilized on plastic plates. PMID- 7985795 TI - Multiple in vitro site-directed mutagenesis using asymmetric polymerase chain reaction. PMID- 7985796 TI - Mobility of digoxigenin-dUTP polymerase chain reaction products and detection of single-stranded products in agarose electrophoresis. PMID- 7985797 TI - A method of using heavy mineral oil for performing "hot-start" amplification of rare nucleic acids. PMID- 7985798 TI - Direct spectrophotometric measurement of enzyme activity in heterogeneous systems with insoluble substrate or immobilized enzyme. PMID- 7985799 TI - Protein purification for microsequencing by sequential native and denaturing polyacrylamide gel electrophoresis: application to one chitinase. PMID- 7985800 TI - Multiple use of blotted polyvinylidene difluoride membranes immunostained with nitro blue tetrazolium. AB - A simple procedure for reusing polyvinylidene difluoride membranes with bound proteins reacted with antibodies and developed by the nitro blue tetrazolium method (M. S. Blake, K. H. Johnston, G. J. Russell-Jones, and E. C. Gotschlich (1984) Anal. Biochem. 136, 175-179) is described. The blue diformazan precipitate produced by the reduction of the nitro blue tetrazolium salt was dissolved by soaking the membrane in dichloro- or trichloromethane for 10-60 min at room temperature. After equilibration in methanol and then in distilled water the first and second antibodies were removed by incubating the membrane in 0.2 M glycine-HCl buffer, pH 2.2, for 90 min at room temperature. These cleaned membranes could be successively reused with different monoclonal antibodies or preimmune serum up to 21 times. The intensity of the spots or electroblotted bands and their specific reaction pattern with different monoclonal antibodies remained unchanged, and no background was observed when the membranes were reacted with preimmune serum. This procedure makes it possible to reuse membranes freshly developed or stored for long periods without loss of resolution. PMID- 7985801 TI - The measurement of beta-phenylethylamine in human plasma and rat brain. AB - A sensitive and specific analytical method has been developed for the measurement of beta-phenylethylamine (PEA) in human plasma and rat brain extracts. The method involves solvent extraction of PEA with cyclohexane in the presence of amphetamine or phenylpropylamine (PPA) as internal standards. Automated precolumn derivatization with o-phthalaldehyde and 2-mercaptoethanol followed by reverse phase HPLC separated PEA and PPA from endogenous interferences. Detection and quantification were carried out by amperometric detection at +0.75 V relative to a Ag/AgCl reference electrode or by coulometric detection with analytical cell potentials set at +0.29 and +0.50 V. The limit of detection for PEA was 10 pg and the limit of quantification in plasma was 60 pg/ml. The within-day and day-to-day coefficients of variation were 16.1% (n = 3) and 40.6% (n = 8), respectively, at a plasma concentration of 154 pg/ml and 15.2% (n = 5) and 28% (n = 10) at a brain extract concentration of 110 pg/ml. Basal endogenous plasma PEA concentrations of 335 +/- 255 pg/ml (n = 12, range 127-1002 pg/ml) were found for normal volunteers and single, daily doses of 24 mg but not 12 mg of the MAO-B inhibitor, mofegiline, were shown to increase plasma PEA significantly. Basal whole brain and striatal concentrations were 0.584 +/- 0.243 ng/g wet wt (n = 3) and 2.89 +/- 1.03 ng/g wet wt (n = 4), respectively. Statistically significant increases (5.7 fold) in rat whole brain PEA concentrations were seen 3 and 6 h following the administration of a single dose of 0.3 mg/kg mofegiline to rats. PMID- 7985802 TI - Quantitative analysis of residual detergent in proteoliposomes by Fourier transform infrared spectroscopy. AB - An infrared spectroscopic method has been developed to quantify the residual amount of detergent present in membranes, e.g., after reconstitution of a membrane protein in phospholipids. A detergent-specific band is selected in the ir spectrum and the intensity is ratioed against a phospholipid-specific band (around 1235 cm-1, vas (P = O)). This ratio shows a linear relation with the molar ratio of detergent of phospholipid, down to as low as 1 to 10. The new method is illustrated in two case studies, viz., tris(hydroxyethyl)ammonium cholate in Na+/K(+)-ATPase proteoliposomes and n-dodecyl-beta-D-maltoside in rhodopsin proteoliposomes. PMID- 7985803 TI - Kinetic applications using high substrate and competitive inhibitor concentrations to determine Ki or Km. AB - Conventional procedures for determining Km or Ki values generally employ subsaturating concentrations of substrate and competitive inhibitor; however, this is impractical in some cases if a significant percentage would be enzyme bound or metabolized. Applications employing high and competing concentrations of substrates and inhibitors are described. Ki or Km values can be calculated from the equations. Ki = [I]/((V0)/V - 1)(1 + [S]/Km)) Km = [S](V0/V - 1)/(1 - V0/V + [I]/Ki), where V0 and V are the rates in the absence and presence of inhibitor. This is illustrated by measurements of inhibition of human urinary kallikrein by synthetic peptides. PMID- 7985804 TI - Colorimetric detection of DNA polymerase activity after sodium dodecyl sulfate polyacrylamide gel electrophoresis. AB - A nonradioactive method is developed to detect DNA polymerase activity after sodium dodecyl sulfate (SDS)-polyacrylamide gel electrophoresis containing gapped DNA as template. The technique is based on the use of digoxigenin- or biotin labeled deoxynucleotides during DNA synthesis, and their detection by means of an anti-digoxigenin antibody-alkaline phosphatase conjugate or by a streptavidin alkaline phosphatase conjugate. The detection of the DNA polymerase catalytic subunit is achieved after incubation of the gels with colorimetric alkaline phosphatase substrates. The technique is able to detect nanogram amounts of Escherichia coli DNA polymerase I and picogram amounts of its Klenow fragment. The results with other DNA polymerases and E. coli extracts suggest that this colorimetric detection system could be used for the analysis of an extended range of DNA polymerase enzymes. The method presented in this report offers an alternative to the already described radioactive techniques for detection of DNA polymerase activity after SDS-polyacrylamide gel electrophoresis. PMID- 7985805 TI - High-pressure liquid chromatography assay for quantitatively monitoring spore photoproduct repair mediated by spore photoproduct lyase during germination of uv irradiated Bacillus subtilis spores. AB - The major DNA photoproduct formed upon uv irradiation of Bacillus subtilis spores is the thymine dimer 5-thyminyl-5,6-dihydrothymine, informally referred to as spore photoproduct (SP). A rapid separation technique for detecting and quantitating SP by HPLC was developed to replace traditional paper chromatography. Tritiated thymine and thymine-containing photoproducts from trifluoroacetic acid-hydrolyzed DNA purified from uv-irradiated cells or spores of B. subtilis were identified and isolated from paper chromatograms, subjected to HPLC on a Microsorb phenyl 5-microns column using 100% water as the mobile phase, and detected by scintillation counting of collected fractions. At a flow rate of 1.8 ml per minute, thymine-containing compounds eluted in the order thymine (T; 5.5 min), cis-syn cyclobutyl thymine-thymine dimers (TT; 7.5 min), cyclobutyl uracil-thymine dimers (UT, the acid breakdown product of cytosine thymine (CT) dimers; 9.5 min), and SP (14.5 min). The method was used to quantitate the amount of SP produced upon irradiation of B. subtilis spores and to monitor repair of SP in vivo by the enzyme SP lyase during spore germination. PMID- 7985806 TI - Analysis of glycoproteins separated by two-dimensional gel electrophoresis using lectin blotting revealed by chemiluminescence. AB - The carbohydrate structures of blotted glycoproteins can be analyzed by probing with lectins. The objective of the present work was to optimize the lectin blotting of human plasma glycoproteins separated by two-dimensional gel electrophoresis and the detection by the sensitive chemiluminescence method. The proposed detection method was found to be ten times more sensitive than a standard colorimetric reaction. Furthermore, the generated signals are detected on a X-ray film and provide a permanent record. The method is also very reliable when compared to the colorimetric detection. The present procedure for glycoprotein analysis is particularly well suited for screening changes in glycosylation of proteins in biological samples. PMID- 7985807 TI - Isolation of myosin heavy chain from small skeletal muscle samples by preparative continuous elution gel electrophoresis: application to measurement of synthesis rate in human and animal tissue. AB - A convenient procedure for the isolation of milligram quantities of myosin heavy chain (MHC) from small samples of muscle tissue using preparative gel electrophoresis is described. Application of the methodology to measurements of the fractional synthesis rates (ks) of MHC using skeletal muscle biopsy samples from humans and cardiac tissue from pigs following continuous intravenous infusions of stable isotope (L-[1-13C]-leucine) is demonstrated. The sensitivity and reproducibility of the determination of stable isotope enrichment are also defined. In addition, measurements of the ks of MHC in skeletal muscle of rats in vivo using radioisotope-tracer methodologies are described. PMID- 7985808 TI - Proteolyses of a fluorogenic insulin derivative and native insulin in reversed micelles monitored by fluorescence emission, reversed-phase high-performance liquid chromatography, and capillary zone electrophoresis. AB - The preparation and substrate properties of the fluorogenic insulin derivative N alpha A1-aminobenzoyl-N epilson B29-Tyr(NO2)- insulin are described. This semisynthetic protein intramolecularly quenched by long-range resonance energy transfer between the donor/acceptor pair 2-aminobenzoic acid and 3-nitrotyrosine was used to prove the activity of serine proteases toward substrates of high molecular weight after incorporation in reversed micelles. The proteases investigated, trypsin and alpha-chymotrypsin, were shown to be hydrolytically active in reversed micellar solvent systems stabilized by cetyltrimethylammonium bromide or sodium-1,2-bis(2-ethylhexylcarbonyl)-1- ethane sulfonate. Apart from fluorometric enzyme assays, methods for monitoring proteolyses in reversed micelles were elaborated using either reversed-phase high-performance liquid chromatography or capillary zone electrophoresis. Enzymatic digestions of native insulin by the specific protease trypsin and the less specific protease alpha chymotrypsin were performed. In contrast to aqueous solution, high but still variable specificity of alpha-chymotrypsin which was dependent on the micellar environment was observed. The results promise further insight into the influence of interfacial environments on enzyme action and a novel approach to enzyme mediated protein modifications by the use of microstructured solvent systems. PMID- 7985809 TI - The rostrocaudal organization in the dorsal root ganglia of the rat: a consequence of plexus formation? AB - The dorsal root ganglia (DRGs) of the rat have a rostrocaudal organization. This organization can most easily be demonstrated in fetal and neonatal rats because the spatial relationships of their DRGs are maintained better in tissue sections than those of mature rats. This review is concerned with the way in which the rostrocaudal organization of the DRGs is generated. Wheat germ agglutinin- horseradish peroxidase/horseradish peroxidase labeling of peripheral nerves of the brachial and lumbar plexuses shows that the position of the somata of the sensory neurons of the labeled nerves can be restricted to rostral or caudal halves of DRGs. Labeling of the thoracic nerve or its branches always results in labeling throughout the entire thoracic DRG. After application of the marker to forelimb nerves, it was observed that whenever a DRG is labeled only partially, its spinal nerve is correspondingly labeled partially as well. These data suggest that the rostrocaudal organization in the DRG is related to the formation of the plexuses. During development nerve fibers can be segmentally labeled, using the subdivision of the DRGs into a rostral and a caudal half to keep together as they find their way through the plexus. Application of label to forelimb skin, hindlimb skin and even thoracic skin can result in labeling of rostral or caudal halves of a DRG. A possible explanation might be that each dermatome can be divided into a skin area innervated by the rostral half of a DRG and a skin area innervated by the caudal half of the same dorsal root ganglion. In the rat, the segmental sensory innervation of muscles during development has not yet been investigated. The question of whether the segmental unit of innervation of a muscle is a whole DRG or half a DRG therefore still remains unanswered. PMID- 7985810 TI - Ectopic ossicles associated with metacercariae of Apophallus brevis (Trematoda) in yellow perch, Perca flavescens (Teleostei): development and identification of bone and chondroid bone. AB - This paper describes the development and tissues in mineralized ossicles in the musculature of Perca flavescens infected with metacercariae of the trematode Apophallus brevis. Analysis involved light microscopy, transmission and scanning electron microscopy, X-ray scanning electron microprobe analysis, and tetracycline labelling. Two to 14 days post-infection, fibroblast-like host cells stream towards the parasite cyst forming a fusiform cellular capsule. By 14 days post-infection the capsule differentiates into an inner hypertrophied layer, an extensive middle layer of fibroblast-like cells, and a thin outer layer of flattened fibroblast-like cells forming a fibrous sheath at the capsule/muscle interface. From 21-35 days post-infection, a bony tissue is deposited periosteally in an equatorial ring around the cyst. With time, additional tissue is secreted over the ring increasing its thickness and advancing the matrix front towards the poles of the ossicle. Plump osteoblast-like cells cover the developing ossicle and may become trapped within the matrix in lacunae encapsulated by collagen. By 63 days post-infection, medium-sized ossicles are morphologically similar to large cysts from perch captured in the wild; ovoid with two polarized canals, but lacking acellular or lamellar bone-like tissue. Mineralized ossicles contain calcium, phosphorus and oxygen. Large ossicles retrieved from perch given multiple doses of tetracycline revealed discrete fluorescent bands, indicative of incremental growth. Fully developed ossicles are composed of two skeletal tissues, an inner region of chondroid bone and an outer region of acellular, lamellar bone. PMID- 7985811 TI - An immunohistochemical study of protein kinase C distribution in fetal mouse vertebral column. AB - Using polyclonal antibodies we have studied the distribution of protein kinase C in fetal mouse low thoracic vertebrae. By means of a pan protein kinase C antiserum recognizing the catalytic domain of the enzyme, we show that protein kinase C is markedly expressed in chondrocytes before birth. The enzyme seems to be very abundant in the more mature cells that are close to ossification centres as well as the periphery of the intervertebral disc, although it can also be detected in chondrocytes. In order to establish which protein kinase C isoenzyme(s) the chondrocytes produce, we employed polyclonal isoenzyme-specific antisera developed against three calcium-dependent isoforms (alpha, beta, gamma) and three calcium-independent isoforms (delta, epsilon, zeta). Secondary antibody conjugated to alkaline phosphatase revealed that chondrocytes markedly express the beta-isoform. Cells were also weakly stained by the anti-epsilon serum. The immunostaining was completely abolished by pre-incubating primary antibodies with the peptide antigens to which they were raised. These results suggest that protein kinase C (and particularly the beta isoform) could play an important role in mouse fetal chondrogenesis of the vertebral column. PMID- 7985812 TI - Neuropeptide Y immunoreactive axons in the corpus callosum of the cat during postnatal development. AB - Many immunocytochemical studies have identified different types of neurotransmitters localized in the corpus callosum (CC) axons in the adult mammal. Few studies have looked at the development of different neurochemically identified CC systems. Previous studies on the development of cat CC axons have indicated that a large number of transitory CC axons project to the cortex during early postnatal development. The present study focuses on the development of one neurochemically identified group of CC axons in the cat, labeled with an antibody against neuropeptide Y (NPY), to determine if this group participates in transitory CC axonal growth. Cats at specified ages from birth to adulthood were studied with a routine method of immunocytochemistry for antiserum to NPY. NPY immunoreactive (ir) CC axons were detected at all stages examined, from newborn to adult; the peak density occurred during postnatal weeks (PNW) 3-4. During PNW 1-2, the density of NPY-ir CC axons increased gradually; some NPY-ir axons at this age had growth cones located within the CC bundle between the cerebral hemispheres. The density of the NPY-ir CC axons decreased gradually during PNW 5 7, and from PNW 8 to maturity only a few NPY-ir CC axons were observed. These results indicate that at least two types of NPY-ir CC axons (i.e., transitory and permanent) exist during development, and that most of these axons are eliminated or only express NPY-ir for a short period during development. The results also indicate that neurochemical subsets of CC axons participate in the extensive transitory growth observed by means of the membrane tracer DiI but they may follow unique developmental timetables. PMID- 7985813 TI - Ooplasmectomy has no influence on FSH-induced expansion of bovine cumulus investment in vitro. AB - Bovine cumulus-oocyte complexes with or without attached pieces of the mural stratum granulosum were matured with or without FSH in vitro for 24 h. Some complexes were ooplasmectomized (removal of ooplasm) at the onset of culture or after 9 h of culture, and in others the complete oocyte, including the zona pellucida, was removed. At the end of culture, the degree and morphology of corona and cumulus expansion were determined by a subjective scoring system, transmission electron microscopy followed by computerized image analysis, or scanning electron microscopy. In the absence of FSH no expansion was seen. In the presence of FSH, hyaluronidase-sensitive cumulus expansion was observed in intact complexes and complexes ooplasmectomized after 9 h of culture. In complexes ooplasmectomized at the start of culture, hyaluronidase-insensitive expansion of the corona compartment was seen as well. A similar reaction was found in free corona and cumulus cell masses cultured in the presence or absence of oocytes. Mural granulosa in intact and ooplasmectomized complexes expanded only slightly under the influence of FSH and exhibited no hyaluronidase sensitivity. Ooplasmectomy at the start of culture increased the frequency of ruffled cell membranes and decreased the occurrence of intercellular bridges as compared with unmanipulated complexes cultured under corresponding conditions. It is concluded that FSH-induced cumulus expansion and hyaluronidase-sensitive extracellular mucus production of bovine cumulus investment in vitro are not dependent on the oocyte, except for minor changes in the surface morphology of the cumulus cells. PMID- 7985814 TI - Developmental changes in nerve growth factor (NGF) binding and NGF receptor proteins trkA and p75 in the facial nerve. AB - This study characterizes the temporal-spatial distribution of nerve growth factor (NGF) low (p75) and high-affinity (trkA) receptors in the facial nerve and geniculate ganglion (GG) of developing quail embryos (E-3 to E-14). We used 125I labeled NGF (125I-NGF) to study binding dynamics in a temporal series of isolated primordia and an autoradiographic series of staged specimens to characterize the occurrence and distribution of NGF receptors in this cranial nerve and its ganglion. In addition, expression of trkA and p75 protein-like immunoreactivity in the facial nerve and GG was studied by Western blot, in order to distinguish between high- and low-affinity NGF receptors respectively. The quantitative study of binding show that isolated facial primordia ranging from E-3 to E-14 exhibit different levels of specific binding. High initial binding levels were observed on E-3 specimens, then an initial decrease on day 4 (E-4) followed by a steady increase from days E-4 to E-7. Maximum 125I-NGF binding was achieved on E-7, followed by a steady decline in binding on days 8 (E-8) and 9 (E-9), reaching near background levels on day 10 (E-10) of development and until the oldest stage assayed (E-14). Most of the cells bearing NGF receptors appeared to be non neuronal crest-derived cells, but some placode-derived neurons and motor fibers of the VIIth cranial nerve transiently expressed the ability to bind 125I-NGF. The temporal pattern of p75 expression matches the pattern of quantitative binding of NGF, while the trkA expression is restricted to a few stages mainly E7 and E9, implying that most of the binding detected is via low-affinity receptors, except for a proportion of high-affinity receptors present at stages of maximum binding. This temporal pattern of NGF binding sites suggests that cells within the VIIth cranial nerve are responsive to and/or dependent upon NGF in vivo, so NGF may play a biological role during normal development of the facial nerve. In view of the developmental events that parallel the occurrence and type of NGF binding sites, we suggest that this role may be to modulate from earlier chemotaxis and cell proliferation to much later events, such as neuronal differentiation and neuron-glia interactions. The significance of these findings in regeneration during adult life remain to be investigated. PMID- 7985815 TI - Organization of the serotoninergic system in the brain of two amphibian species, Ambystoma mexicanum (Urodela) and Typhlonectes compressicauda (Gymnophiona). AB - An immunocytochemical investigation was made of the distribution of serotonin (5 HT) in the brain of larval and adult Ambystoma mexicanum and adult Typhlonectes compressicauda. Immunoreactive perikarya can be identified in the caudal diencephalon (paraventricular organ and infundibular nucleus), in the ventral mesencephalon (interpeduncular nucleus) and in the raphe of the rhombencephalon. Immunopositive fibers and terminal arborizations are widely distributed, extending from the whole telencephalon to the spinal lemniscus area. However, the retinorecipient structures of the thalamus and mesencephalon are either very weakly innervated (Ambystoma) or completely immunonegative (Typhlonectes). The habenular system also exhibits very few 5-HT-positive structures. The major serotoninergic neuron clusters, in both Urodela and Gymnophiona, tend to gather, from the paraventricular organ to the raphe, on both sides of the sagittal plane, showing no tendency to "lateralization". A new interpretation of the limited development of the serotoninergic system in amphibians is given. PMID- 7985816 TI - Antibiotic resistance: will infection control meet the challenge? PMID- 7985817 TI - Epidemiologic perspectives on Enterobacter for the infection control professional. AB - Enterobacter species have emerged as important nosocomial pathogens. Common reservoirs for these organisms include wounds and the gastrointestinal, urinary, and respiratory tracts. Enterobacter bacteremia typically occurs in patients with long-standing underlying illnesses who received antimicrobial agents before their bacteremia. The wide use of broad-spectrum antibiotics has contributed to the increased prominence of Enterobacter infections. Enterobacter species have a propensity to emerge resistant to the antibiotic therapy administered. Plasmid analysis, restriction endonuclease analysis of total cellular DNA, pulsed-field electrophoresis, and ribotyping can be valuable in investigating the spread of antibiotic-resistant strains. PMID- 7985818 TI - Colonization pattern of vancomycin-resistant Enterococcus faecium. AB - BACKGROUND: Vancomycin-resistant Enterococcus faecium is increasingly recognized as a serious problem by hospital epidemiologists. Understanding its colonization patterns may help in designing strategies to control its nosocomial spread in the hospital. METHODS: Twenty patients, selected at random, with vancomycin-resistant E. faecium isolated from cultures of various body sites were studied to determine sites of colonization. For 12 of these patients, cultures of environmental surfaces of their rooms and wards were also obtained. RESULTS: Eighteen patients (90%) had vancomycin-resistant E. faecium grown in stool cultures. In five patients (25%), vancomycin-resistant E. faecium was cultured from other sites: groins (four), popliteal fossae (three), mouth (one), and an open wound site (one). Patients with positive cultures from the groins and popliteal fossae also had growth of vancomycin-resistant E. faecium in cultures of diarrhea soiling those sites. No patients had the organism isolated from their nares. Vancomycin resistant E. faecium grew in cultures obtained from bedside stand tables, over bed tables, used linen, and bedside rails. CONCLUSIONS: In the 20 patients studied, colonization of vancomycin-resistant E. faecium was limited chiefly to the enteric tract. Absence of colonization of such a secluded area with poor antibiotic penetrability as the nares is encouraging. In our study, vancomycin resistant E. faecium was isolated from various environmental surfaces from the rooms and wards of patients with vancomycin-resistant E. faecium in their stools. PMID- 7985819 TI - Demand for isolation beds in a pediatric hospital. AB - OBJECTIVE: To determine isolation bed use for community-acquired and nosocomial infections in a pediatric hospital. DESIGN: A prospective repeated point prevalence survey was conducted during a 14-month period. A questionnaire was sent to other free-standing Canadian children's hospitals to determine isolation practice and perceived needs. SETTING: A university-affiliated, 218-bed pediatric hospital in Halifax, Nova Scotia, Canada. PATIENTS: All inpatients on surveyed wards during the study period (n = 1634). RESULTS: Overall, 13.5% of patients required isolation (range 5.6% to 31% per month). Demand was seasonal, with 71% of isolation occurring from November to April. Demand exceeded supply by 2 to 22 beds (11% to 122%). Respiratory and enteric infections requiring contact isolation accounted for 80% of use (53% and 27%, respectively). Children younger than 24 months comprised 28% of admissions and used 57% of isolation beds. Of patients isolated, 25% had nosocomial infections and 75% had community-acquired infections. The percentage of infant rooms in Canadian children's hospitals that were single bed (considered optimal for infant isolation) varied: 0% to 20% for hospitals built before 1965 and 25% to 47% for newer hospitals. All hospitals with less than 33% single-bed infant rooms perceived this allocation to be inadequate (p < 0.01 Fisher Exact Test). CONCLUSIONS: Pediatric isolation bed use varies with patient age, season of year, and category-specific isolation requirements. An increasing need for single-bed rooms is identified. Isolation requirements must be considered during the design of new hospitals or renovation of existing ones. PMID- 7985820 TI - Hospital carpeting and epidemiology of Clostridium difficile. AB - BACKGROUND: Clostridium difficile is the usual and most important cause of antibiotic-associated pseudomembranous enterocolitis. The source of nosocomial acquisition of the organism in nonepidemic settings has not been determined. METHODS: Epidemiologic and microbiologic studies were conducted in a community teaching hospital complex to assess the impact of carpeting in patient rooms on environmental contamination with C. difficile, along with the prevalence of pseudomembranous enterocolitis. All C. difficile isolates were typed by means of a bacteriophage-bacteriocin typing scheme. RESULTS: No clear evidence of environmental acquisition of C. difficile in a nonepidemic setting of pseudomembranous enterocolitis was found. Carpeted floors were significantly more heavily contaminated for prolonged periods with clinical strains of C. difficile than were noncarpeted floors. CONCLUSION: There was no evidence that contamination of carpeting resulted in increased frequency of pseudomembranous enterocolitis in patients residing in carpeted rooms. Because there is strong evidence of exogenous acquisition of C. difficile during outbreaks, however, room carpeting should be considered a potential reservoir of this organism. PMID- 7985821 TI - Use of image analysis to measure handwashing effectiveness. AB - BACKGROUND: This study tested a unique quantification technology (image analysis of fluorescent particles) for the measurement of handwashing effectiveness, comparing an automated system with traditional manual handwashing. In this instance, handwashing "effectiveness" was defined as ability of the technique to remove surface soil, as opposed to removal of microorganisms. METHODS: Sixty-five subjects washed their hands by manual handwashing (day 1) and automated handwashing (day 2). Hands were coated with an oil-based fluorescent suspension, photographed under controlled conditions, washed for 10 seconds, and rephotographed. Photographs from before and after handwashing were subjected to image analysis. RESULTS: Manual handwashing removed 73.1% of the particles; the automated method removed 23.2%. Parameters for use of image analysis as a technique to examine removal of gross contamination from the hands are given in the text. CONCLUSIONS: Although this method will not replace traditional culture methods for examining microbial removal, it is useful for measuring removal of particles (gross contamination) from skin or other surfaces. Under the conditions tested, manual handwashing was found to be decidedly superior to use of an automated system for removal of oil-based soil on the hands. PMID- 7985822 TI - Comparative effectiveness of hand-cleansing agents for removing methicillin resistant Staphylococcus aureus from experimentally contaminated fingertips. AB - BACKGROUND: Five subjects participated in a study of optimal conditions for removing methicillin-resistant Staphylococcus aureus from contaminated fingertips. METHODS: Fingertips were contaminated experimentally and cleaned by various methods. Bacterial removal was measured as percentage and is given as mean +/- standard error of the mean. RESULTS: Rinsing the fingertips with tap water for 20 seconds and drying them with paper towels removed 95.2% +/- 1.6% of the contamination. Application of hand-cleansing agents to fingertips for 20 seconds, followed by a 20-second tap-water rinse and towel drying, removed bacteria as follows: povidone-iodine detergent, 99.2% +/- 0.4%; chlorhexidine detergent, 97.2% +/- 0.8%; and liquid soap, 96.1% +/- 1.1%. In a modification of the method, 80% ethyl alcohol applied to the fingertips for 20 seconds, followed by air drying for 40 seconds, removed 99.1% +/- 0.8% of the bacteria. Statistical analyses indicated that povidone-iodine and 80% ethyl alcohol were more effective than the other agents. CONCLUSIONS: Rinsing contaminated fingertips with tap water and towel drying them is sufficient to reduce contamination with methicillin-resistant S. aureus by 95%. Washing with povidone-iodine or 80% ethyl alcohol further reduces contamination by an additional 99%. PMID- 7985823 TI - Handwashing machines, handwashing compliance, and potential for cross contamination. AB - Although handwashing is considered an important factor in the prevention of nosocomial infections, the optimal technique has not been determined and compliance is often difficult to obtain. Handwashing compliance is particularly important in intensive care areas of the hospital. In an effort to improve HW compliance, the surgical intensive care unit in our hospital purchased three handwashing machines. Four months after installation of the handwashing machines, an outbreak of methicillin-resistant Staphylococcus aureus occurred in the intensive care unit. As part of evaluating the outbreak, we cultured the handwashing machines, including the portholes and the paper towel dispenser. Cultures were positive for methicillin-resistant Staphylococcus epidermidis, Achromobacter species, and Streptococcus viridans. The design of the handwashing machines made contamination of sleeves and already-washed hands possible. An observational study revealed that handwashing compliance was poor but improved from 22% to 38% when the handwashing machines were in use. Nurses preferred handwashing at the sink and physicians preferred the handwashing machine. Handwashing machines may increase handwashing compliance because of their novelty, but they may also result in novel problems. PMID- 7985824 TI - Surveillance of intravenous catheter-related infections among home care clients. AB - BACKGROUND: Infection control in home care is an important area of study, and infection related to home infusion therapy is one component. METHODS: According to billed supplies from a 6-month period, we identified clients receiving intravenous care and conducted a chart review to determine characteristics and infection status. We reviewed each client from the start of a continuous home care period through April 30, 1992. RESULTS: Care of the catheters was done by nurses, family care givers, or the clients themselves. Intravenous catheter related infections-site infections and bacteremia-occurred in three (4.5%) of the sample of 67; bacteremia occurred in one (1.5%). Incidence density was 12.5 infections per 10,000 catheter days (4.2 bacteremias per 10,000 days). Among those with central lines who remained without infection, 22.9% had the same line in place for 90 days or more. Among those with peripheral lines who remained without infection, 14.3% had a peripheral line, which was changed during home care, for 30 days or longer. CONCLUSIONS: Home care agencies seeking accreditation from the Joint Commission on the Accreditation of Healthcare Organizations need to establish surveillance systems; this may be one method to monitor device-related infections and to determine baseline rates. PMID- 7985825 TI - Tuberculosis surveillance: lessons from a cluster of skin test conversions. AB - Mycobacterium tuberculosis has reemerged as a significant public health problem. Elderly persons, especially those in long-term care facilities, are among those at high risk for infection with M. tuberculosis. Frequently, their symptoms are not clearly indicative of M. tuberculosis, and the diagnosis may thus be missed. We discuss the investigation of a cluster of skin test conversions on one locked unit in our long-term care facility. During the epidemiologic investigation, four of 25 patients who had previously had negative results of purified protein derivative testing (16%) and eight of 95 employees (11%) had skin test conversions. Despite a comprehensive, costly evaluation, the index case was not found. We identified weaknesses in our employee and patient M. tuberculosis surveillance programs. Employee baseline purified protein derivative testing data were inadequate. Annual skin tests for employees with previously negative results were not mandatory. There was no mechanism in place to encourage compliance. We developed a plan to educate personnel about the reemergence of M. tuberculosis, signs and symptoms in elderly patients, and the placement and interpretation of purified protein derivative skin tests. Documentation of purified protein derivative surveillance of both patients and employees was computerized. The number of inpatient and outpatient negative-pressure rooms was increased. Appropriate personal protective equipment was made available for use in high-risk situations. PMID- 7985826 TI - Guideline for prevention of nosocomial pneumonia. The Hospital Infection Control Practices Advisory Committee, Centers for Disease Control and Prevention. PMID- 7985827 TI - Inferior vena caval thrombosis associated with acute pancreatitis: an unusual vascular complication--its presentation and management. AB - Vascular thrombosis and systemic hypercoagulable states are known complications of acute pancreatitis. They are thought to be secondary to the release of proteolytic enzymes of the pancreas. Inferior vena caval thrombosis is an extremely rare complication of chronic pancreatitis and has, to the authors' knowledge, never been reported in acute pancreatitis. The clinical presentation and radiographic findings are reviewed to illustrate the disease spectrum. Early treatment with intravenous heparin appears to be an effective therapy. Familiarity with this complication will aid physicians in its early diagnosis. However, a high degree of suspicion for this complication is necessary to make a diagnosis. PMID- 7985828 TI - Plasma levels of tumor necrosis factor and endothelial response in patients with chronic arterial obstructive disease or Raynaud's phenomenon. AB - Tumor necrosis factor alpha (TNF-alpha) is a cytokine that affects endothelial cells' function by changing their antithrombotic potential to a net procoagulant effect. Only a few data have so far been reported for the pathophysiologic role of TNF in vascular diseases in the involvement of microvessels and/or macrovessels and a prothrombotic state. In the present study the authors evaluated plasma TNF (and interleukin-1) levels in 20 patients with chronic arterial obstructive disease (CAOD) with intermittent claudication and 10 CAOD patients with more severe disease (pain at rest/skin ulcers). In addition, they studied 10 patients with Raynaud's phenomenon (RP), suspected to be secondary to a collagen disease. The control group consisted of 20 subjects matched for sex and age with the three groups of patients. TNF levels were assayed by enzyme linked immunosorbent assay. The antigen levels of von Willebrand factor (vWF), tissue plasminogen activator (t-PA), and its inhibitor (PAI) were also determined as markers of release from the endothelium, while the fragment 1 + 2 of prothrombin (F1 + 2) and thrombin-antithrombin III (TAT) complexes were assessed as indexes of systemic thrombin generation. TNF levels were significantly higher in both groups of CAOD patients than in controls or RP patients, and the same was true for vWF. t-PA was significantly higher only in the CAOD subjects with more severe disease. No differences among groups were seen in PAI antigen/activity or thrombin generation. When data were corrected for age, TNF no longer differentiated CAOD patients from controls and RP subjects.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7985829 TI - Effects of a low-dose fish oil concentrate on angina, exercise tolerance time, serum triglycerides, and platelet function. AB - Fish oils have shown beneficial effects on various parameters in patients with coronary artery disease (CAD). The purpose of this study was to investigate whether the same effects can be demonstrated with a low dose of fish oil concentrate (FOC). Thirty-nine patients were studied and divided into two groups. Twenty were given 10 g fish oil (group A) and 19 were given 10 g placebo Italian olive oil (group B). Weekly anginal attacks (AA), weekly glyceryl trinitrate consumption (GTN), exercise tolerance time (ETT), serum triglycerides (ST), platelet aggregation ratio (PAR), and beta-thromboglobulin were measured at eight and twelve weeks after start of treatment. 1. The number of anginal attacks recorded by both groups decreased by 41% in group A reaching statistical significance (P < 0.05). No change was observed in group B. 2. GTN consumption decreased in group A (P < 0.05) with no significant change in group B (P:ns). 3. ETT increased significantly in group A eight and twelve weeks after start of treatment (20.6% P < 0.01, 22.6% P < 0.01). A smaller but insignificant increase was observed in group B (P: ns). 4. ST decreased significantly in group A by 22% eight weeks after start of treatment (P < 0.01) and to a lesser degree (11%) twelve weeks after start of treatment (P: ns). In group B, ST slightly increased (P: ns). 5. No statistically significant change was observed in either group in regard to PAR and beta-thromboglobulin (P: ns). These observations suggest that dietary supplementation with a low dose of FOC may have beneficial effects on the clinical status of patients with CAD.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7985830 TI - Left ventricular remodeling and function in adult aortic stenosis. AB - The aim of this study was to analyze the left ventricular (LV) geometric changes occurring in chronic pressure overload due to valvular aortic stenosis (AS). Fifty-six adult patients (30 women, 26 men, mean age seventy-two +/- nine years, range forty-five to eighty-five years) with isolated AS (mean valve area by Doppler = 0.6 +/- 0.2 cm2) underwent a complete Doppler echocardiographic examination. According to the value of relative wall thickness (RWT = 2 x posterior wall thickness/LV end-diastolic diameter) and LV mass index (LVMI) in normal subjects (RWT < or = 0.44, LVMI < or = 125 gr/m2) AS patients were subdivided into four groups: Normal: no patients; Concentric Remodeling RWT > 0.44, LVMI < or = 125 gr/m2): 4 patients (7%); Concentric Hypertrophy (RWT > 0.44, LVMI > 125 gr/m2): 39 patients (70%); and Eccentric Hypertrophy (RWT < or = 0.44, LVMI > 125 gr/m2): 13 patients [23%]. Eccentric hypertrophy patients had, as compared with those with concentric hypertrophy, a larger left ventricle (61 +/- 6.5 mm vs 47.6 +/- 6 mm, P < or = 0.001), a smaller mean wall thickness (11.3 +/- 1.2 vs 14.7 +/- 1.7 mm, P < 0.001) and reduced LV fractional shortening (FS% = 22.9 +/- 11 vs 42.6 +/- 8.7%, P < 0.001). Furthermore, most patients (11/13) of the former group had heart failure due to LV systolic dysfunction, while only 16 of 39 patients of the latter group had heart failure and all but 2 had normal LV systolic function.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7985831 TI - Compressions of carotid and vertebral arteries in assessment of intracranial collateral flow: correlation between angiography and transcranial Doppler ultrasonography. AB - The authors examined 61 subjects with carotid angiography and 50 with vertebral angiography. Angiograms were evaluated for collateral flow through the ophthalmic, anterior communicating, and posterior communicating arteries. The authors evaluated the patency of collateral vessels directly using transcranial Doppler ultrasonography; they made indirect detection after the compression of carotid and vertebral arteries while monitoring flow velocities in the middle cerebral artery. They established criteria for the hemodynamic significance of tested collateral vessels. A combination of carotid compressions and transcranial Doppler ultrasonography detected the patency of the ophthalmic and anterior communicating arteries with a specificity and sensitivity of 1.00. Examination of the posterior communicating artery had a sensitivity of 0.97 and specificity of 0.98. Indirect evaluation of collateral vessels can not only detect their presence but also establish their hemodynamic significance with high accuracy. PMID- 7985833 TI - Temporal arteritis associated with acute Q fever. A case report. AB - The authors describe the case of a sixty-four-year-old man who presented with clinical and histopathologic evidence of temporal arteritis associated with acute Q fever. This association, which has not been previously reported, supports the possible infectious etiology in temporal arteritis. PMID- 7985832 TI - Prevalence of infection from subclavian dialysis catheters with two different postinsertion catheter cares: a randomized comparative study. AB - A comparison of the outcome of two different protocols concerning the postinsertion catheter care are reported and the literature of the subject is reviewed. Forty patients had the "Quinton" double-lumen catheter in the subclavian vein for hemodialysis. These catheters were kept in place for a total of 1392 days. The patients were divided randomly into two groups (A and B), each consisting of 20 patients. The care of group A catheters was done by the hospital intravenous (IV) team using heparin flushing three times/day. The care of group B catheters was done by dialysis nurses using heparin 1 mL of 2500 units in each lumen only after dialysis, ie, three times/week. The bacteremia rate of group A was 15% while that of group B was 5%. In conclusion, flushing the catheter with heparin 1 mL/2500 units in each lumen of the catheter at the end of dialysis, ie, three times/week along with changing the dressing once per week were found valuable in decreasing the rate of bacteremia from catheter infection. PMID- 7985834 TI - Measurements of human coronary vascular impedance. AB - The aim of this study was to develop a method of measuring human coronary circulation impedance in a clinical setting. The authors measured coronary flow reserve (CFR) in 27 patients with chest pain and normal coronary arteries. A Judkins-style, 8F Doppler-tipped angiographic catheter was positioned in the left coronary ostium. Resting coronary flow velocity (RFV) and response to a hyperemic 12 mg intracoronary dose of papaverine (PFV) were measured. The signals were recorded by a recorder connected to a microprocessor with analogue-to-digital converter and a maths coprocessor. Using this the authors could obtain values for impedance at RFV (IR) and at PFV (IP). The CFR was defined as the ratio: PFV/RFV. An impedance index (II) was obtained as the ratio of coronary vascular impedance at peak hyperemia to the impedance at rest. The CFR was 3.2 +/- 1.2 and the II was 0.33 +/- 0.11. There was a strong inverse correlation between the CFR and the II (r = -0.9). The authors conclude that this new approach may allow a further insight into the coronary pathophysiology and may become useful in clinical cardiology, eg, in the assessment of heart transplant and Syndrome X patients. PMID- 7985835 TI - Antihypertensive therapy with isradipine in patients with special safety concerns. AB - Treatment of hypertension in the complicated patient requires a specialized approach focusing on the treatment of the blood pressure and concurrent medical problems. Therapy must be chosen in consideration of the patient's age, multiple illnesses, declining organ function, and possible drug interactions. This requires that the antihypertensive agent chosen have a demonstrated safe profile. In clinical trials, monotherapy with the calcium channel blocker (CCB) isradipine (ISR) at a recommended therapeutic dosage has controlled blood pressure with an excellent level of safety. In these studies, ISR had no significant effect on heart rate, cardiac conduction, or cardiac contractility and no negative effect on renal function. In hypertensive patients with both normal and impaired renal function, ISR significantly increased renal plasma flow while decreasing renal vascular resistance without decreasing glomerular filtration rate and filtration fraction. ISR has long-term natriuretic effects that may provide additional benefits in antihypertensive therapy. Most adverse effects associated with ISR are mild, transient, and related to vasodilation. The most frequently reported adverse reactions are headache, dizziness, and edema. ISR does not affect glycemic control or lipid metabolism in either diabetic or nondiabetic patients. It has no reported adverse interaction with some of the most commonly used medications for elderly patients, including digoxin, nitroglycerin, oral hypoglycemics, and hydrochlorothiazide. ISR may be used as a first-line agent for the treatment of hypertension in complicated patients. PMID- 7985836 TI - Direct characterization of bovine microsatellites from cosmids: polymorphism and synteny mapping. AB - A (TG)8 oligonucleotide probe was used to screen 186 cosmids from a commercial bovine cosmid library. Of the 56 positive discovered, 7 were sequenced in the region of the microsatellite and analysed for polymorphism. These microsatellites, IDVGA-2, -3, -7, -8, -9, -10, -11 showed the following number of alleles and polymorphism information content (PIC) values (7/0.616, 8/0.693, 6/0.641, 5/0.643, 2/0.239, 10/0.844, 6/0.720). The microsatellites were also assigned to synteny groups as follows: IDVGA-2/U17, IDVGA-3/U16, IDVGA-7/U7, IDVGA-8/U29, IDVGA-9/U3, IDVGA-10/U19, IDVGA-11/A (probably U18). PMID- 7985837 TI - Polymorphic sequence in the D-loop region of equine mitochondrial DNA. AB - The D-loop regions in equine mitochondrial DNA were cloned from three thoroughbred horses by polymerase chain reaction (PCR). The total number of bases in the D-loop region were 1114 bp, 1115 bp and 1146 bp. The equine D-loop region is A/T rich like many other mammalian D-loops. The large central conserved sequence block and small conserved sequence blocks 1, 2 and 3, that are common to other mammals, were observed. Between conserved sequence blocks 1 and 2 there were tandem repeats of an 8 bp equine-specific sequence TGTGCACC, and the number of tandem repeats differed among individual horses. The base composition in the unit of these repeats is G/C rich as are the short repeats in the D-loops of rabbit and pig. Comparing DNA sequences between horse and other mammals, the difference in the D-loop region length is mostly due to the difference in the number of DNA sequences at both extremities. The similarities of the DNA sequences are in the middle part of the D-loop. In comparison of the sequences among three thoroughbred horses, it was determined that the region between tRNA(Pro) and the large central conserved sequence block was the richest in variation. PCR primers in the D-loop region were designed and the expected maternal inheritance was confirmed by PCR-RFLP (restriction fragment length polymorphism). PMID- 7985838 TI - A microsatellite within the bovine kappa-casein gene reveals a polymorphism correlating strongly with polymorphisms previously described at the protein as well as the DNA level. AB - The polymorphism of a (TA)n(CA)n repeat microsatellite present in the third intron of the bovine kappa-casein gene (CASK) has been investigated. The existence of six alleles differing only in the number of dinucleotide repeats has been established. A total of 330 animals belonging to nine different pure bred Bos taurus French breeds or to a cross-bred Bos taurus x Bos indicus population (Creole) were genotyped. The distribution of the microsatellite alleles was examined and clear breed differences were noted. Genotyping of animals by isoelectric focusing (IEF) or restriction fragment length polymorphism (RFLP) (TaqI) was performed, in order to examine the relationship of the microsatellite polymorphism to other previously described CASK polymorphisms, at the protein and DNA levels. Strong correlation was seen, indicating that evolution of the various polymorphisms was not independent, and nine CASK haplotypes were observed. PMID- 7985840 TI - Mapping and characterization of the DQ subregion of the ovine MHC. AB - A map of the ovine MHC class II DQ subregion has been constructed from overlapping cosmid clones. This region consists of two loci linked on a linear tract of 130 kb DNA. Each locus consists of a DQA and a DQB gene in a tail-to tail orientation. The genes in each locus are transcribed but only those designated DQ1 express class II molecules at the surface of mouse L cells following DNA-mediated gene transfection. The DQA1 and DQB1 genes are separated by 11 kb while the DQA2 and B2 genes are 25 kb apart. The loci are separated by 22 kb. PMID- 7985839 TI - Expression pattern, genomic cloning and RFLP analyses of the swine PIT-1 gene. AB - The swine PIT-1 POU domain cDNA was used to study PIT-1 expression and to clone the PIT-1 genomic region to identify additional PIT-1 polymorphisms. PIT-1 was expressed only in the pituitary, confirming the swine cDNA identity. To study the PIT-1 genomic region, a clone containing 13.7 kb DNA was isolated. EcoRI fragments hybridizing to PIT-1 were sequenced, and the 3' portion of PIT-1 gene identified. Primers for polymerase chain reaction (PCR)-restriction fragment length polymorphism (RFLP) analysis were then designed. Restriction analysis of PCR products identified a RsaI RFLP. In contrast to other PIT-1 RFLPs, the RsaI PCR-RFLP was widely distributed in American breeds. Thus, the RsaI RFLP and the previously reported PIT-1 RFLPs allow detection of PIT-1 alleles in most, if not all, breeds currently used in the US and European reference/resource pig mapping families. PMID- 7985841 TI - Divergent selection for antibody production in common carp (Cyprinus carpio L.) using gynogenesis. AB - A base population (n = 101) of carp, consisting of a single hybrid cross, was immunized with the hapten-carrier complex DNP-KLH, to perform a divergent selection for antibody response. Measurement of the DNP-specific antibody response at 12 and 21 days postimmunization, allowed the classification of a low number of individual carp as early/high (10%) or late/low (13%) responders. Three individuals defined as early/high and three defined as late/low responding, were gynogenetically reproduced to obtain corresponding homozygous progenies within one generation only. Upon immunization with DNP-KLH, the antibody response was found to be significantly higher in the early/high responder homozygous offspring. Although the homozygosity of the offspring apparently caused a (s)lower antibody response (compared with the base population), the differences between the high and low responder offspring to indicate a genetic influence on the antibody response. The realized heritability (h2) for antibody production was estimated at 0.37 +/- 0.36. The present study provides the basis for a divergent selection of homozygous inbred carp lines with a genetically controlled difference in antibody response. These inbred lines will allow us to investigate relationship(s) between immune responsiveness and resistance to infectious diseases in fish. PMID- 7985842 TI - Mapping quantitative trait loci with DNA microsatellites in a commercial dairy cattle population. AB - Individual loci affecting economically important traits can be located using genetic linkage between quantitative trait loci and genetic markers. In the 'granddaughter' experimental design, heterozygous grandsires and their sons are genotyped for the genetic marker, while the quantitative trait records of the granddaughters are used for statistical analysis. Ten DNA microsatellite markers were used to look for associations with quantitative trait loci affecting milk production traits in seven Israeli Holstein grandsire families. At least 60% more grandsires were heterozygous, and 40% fewer individuals were discarded because of unknown paternal allele origin, as compared with diallelic markers. The effects of paternal alleles for locus D21S4 on kg milk and protein were significant (P < 0.025). The allele substitution effects for sire 783 were 283 kg milk and 5.7 kg protein. For both traits, progeny of sire 783 that inherited allele '18' had higher evaluations than progeny that inherited allele '21'. These results were verified by genotyping 151 of his daughters. Thus, the rate of genetic gain for protein production can be increased by selecting progeny of sire 783 carrying allele '18' at this locus. PMID- 7985843 TI - Mitochondrial genetic variation in European, African and Indian cattle populations. AB - Mitochondrial DNA from representative animals of 13 different cattle breeds was assayed for restriction fragment length polymorphisms (RFLP) to determine phylogenetic relationships and levels of variation among breeds; 16 different mitotypes were found, described by 20 polymorphisms. Within these 16 mitotypes two major lineages were apparent: an Afro-European and an Asian type. These were found to differ at over 2.3% of sites surveyed. None of the mitotypes found in the Asian lineage was detectable in the Afro-European lineage and vice versa. Within each of the major mitotypes there were no further significant differences within or among breeds. Using rates of mitochondrial evolution estimated from other species, the two lineages were estimated to have diverged between 575,000 and 1,150,000 years ago; well outside the 10,000 years bp timeframe postulated by a single domestication hypothesis. The results presented are concordant with those generated in other studies and provide strong evidence for an independent domestication of Asian Bos indicus. Furthermore, the grouping of all African indicine populations within the clade containing all Bos taurus lineages points to the hybrid origins of the humped cattle of that continent. PMID- 7985844 TI - Repetitive plasmid sequences generate DNA fingerprinting patterns in mammals. AB - Bacterial plasmids with stringently regulated copy numbers have directly repeated DNA sequences, termed iterons, in the vicinity of their replication origins. These sequences bind a specific protein exerting a key role in the initiation of plasmid replication. Plasmids P1, pSC101 and RFS1010 have different iteron sequences and belong to three different incompatibility groups. Used as DNA probes each of these plasmids generates specific patterns in mammals similar to those obtained by the DNA fingerprinting technique. The iteron-containing regions were identified as the part of the plasmids responsible for those patterns by using polymerase chain reaction (PCR) amplified DNA segments that contained the iteron regions as probes. PMID- 7985845 TI - Red cell reduced glutathione concentrations in Spanish Churra sheep. AB - Erythrocyte reduced glutathione (GSH) levels were investigated in Spanish Churra sheep. GSH deficiency appeared in a high frequency, a clear bimodal distribution being apparent. No significant concentrations of amino acids were detected in the samples and no significant differences were found in potassium concentrations between the low-GSH and the high-GSH type animals. Such results indicate that erythrocyte GSH deficiency in Churra sheep may be similar to the 'Merino type' GSH deficiency. Furthermore, limited inheritance data suggested that a second type of GSH deficiency might be present also in Churra sheep. PMID- 7985846 TI - Isolation of polymorphic AGC repeats located 3' to bovine SINEs. AB - A bovine genomic library was screened for the presence of (AGC)n repeats. All isolated AGC repeats were located adjacent to the 3' end of bovine short interspersed nuclear elements (SINE). Polymerase chain reactions (PCR) using either two unique primers or one unique and one SINE primer produced high resolution products without the secondary artifact ladders typical of dinucleotide microsatellites. Four AGC microsatellites were found to be polymorphic with 2-4 alleles each and polymorphism information context (PIC) values ranging between 0.26 and 0.49. One microsatellite, ARO25, was mapped to chromosome 26 with the CSIRO reference families. Because of their strong association with AGC repeats and high frequency in the genome, SINE-3' PCR may prove to be a novel source of polymorphic trinucleotide markers in the bovine genome. PMID- 7985847 TI - A PstI RFLP at the porcine orosomucoid locus (ORM). PMID- 7985848 TI - Two new equine dinucleotide repeat microsatellites at the EA2C4 and EB2E8 loci. PMID- 7985849 TI - A dinucleotide repeat in the ovine interleukin-3 gene of limited polymorphism. PMID- 7985850 TI - An EcoRI RFLP at the porcine endothelin-1 locus (EDN1). PMID- 7985852 TI - Detection of aberrant alleles in the D-loop region of equine mitochondrial DNA by single-strand conformation polymorphism (SSCP) analysis. PMID- 7985851 TI - An ApaI polymorphism at the ovine tissue inhibitor of metalloproteinase locus (TIMP). PMID- 7985853 TI - A BglII polymorphism at the ovine phosphorylase kinase alpha subunit locus (PHKA1). PMID- 7985854 TI - The ovine esterase D (ESD) locus carries a high-frequency EcoRI polymorphism. PMID- 7985855 TI - UWCA21: a polymorphic bovine microsatellite. PMID- 7985856 TI - An XbaI RFLP at the locus encoding the chicken homologue of ANX5. PMID- 7985857 TI - Dinucleotide repeat polymorphism near a bovine MHC class I sequence. PMID- 7985858 TI - An ostrich dinucleotide repeat polymorphism at the VIAS-OS2 locus. PMID- 7985859 TI - Equine dinucleotide repeat polymorphism at the VIAS-H7 locus. PMID- 7985860 TI - A TaqI RFLP at the PLAT (plasminogen activator, tissue) locus of sheep. PMID- 7985861 TI - An EcoRV polymorphism at the ovine Menkes disease locus (ATP7A). PMID- 7985862 TI - Ovine microsatellites at the OarHH30, OarHH51, OarVH54, OarCP88, OarCP93, OarCP134 loci. PMID- 7985864 TI - Hourly vs. salaried. Protecting RNs with the Fair Labor Standards Act. PMID- 7985863 TI - Five bovine dinucleotide repeat polymorphisms: RM026, RM029, RM032, RM033 and RM038. PMID- 7985865 TI - Employers use Supreme Court decision against RNs; ANA devises legal, legislative strategies. PMID- 7985866 TI - RNs strike back against unfair staffing and jeopardized patient care. PMID- 7985867 TI - Beginning a job search: take six steps to ensure success. PMID- 7985869 TI - Continuing education program: integrating and understanding of sleep knowledge into your practice (continuing education credit). PMID- 7985868 TI - GNs reap benefits of computerized NCLEX, but at what cost? PMID- 7985870 TI - Boosting careers through CE. PMID- 7985871 TI - Finding opportunity in change: public health, home health and school nursing hold promise for nurses. PMID- 7985872 TI - Community wellness nursing gives older Americans independence. PMID- 7985873 TI - USP and ANA join forces to prevent med errors. PMID- 7985874 TI - Commonly asked questions about ANCC certification. PMID- 7985875 TI - Nurses volunteer for White House communications work. PMID- 7985876 TI - Our career, nursing's future. PMID- 7985877 TI - Grassroots lobbying: a nurse's responsibility. PMID- 7985878 TI - Two nurses tell their stories of the bus trip with a message. PMID- 7985879 TI - Nurses worldwide speak the same language. PMID- 7985880 TI - Embracing and shaping change. PMID- 7985881 TI - Restructuring health care delivery: economically streamlined or simply cheapened? PMID- 7985882 TI - Restructuring: affecting the workforce and workplace for new grads. PMID- 7985883 TI - Wondering if you should join a professional association? ANA has the answers. PMID- 7985884 TI - ANA's strong voice in politics gets results. PMID- 7985885 TI - Memory. When less is more. AB - Loss of memory for the characteristics of stimuli (i.e., forgetting of stimulus attributes) can lead to increases in behavior, a consequence quite different from the impairments associated with the forgetting of responses. Evidence from animal and human research for the forgetting of stimuli as a distinct memory principle is presented, and the methodological and conceptual implications of this pervasive type of memory loss are considered. Malleability of eyewitness memory, cognitive confusions, sleeper and familiarity effects, and temporal distortions in inferences and attributions are among the varied behavioral phenomena that can be accounted for in terms of forgetting of stimulus attributes. PMID- 7985887 TI - The science and politics of race-norming. AB - Disparate impact (racial imbalance) in employee selection constitutes prima facie evidence of unlawful discrimination. Research in personnel psychology has shown, however, that valid and unbiased selection procedures often guarantee disparate impact and that they will continue to do so as long as there remain large racial disparities in job-related skills and abilities. Employers are in a legal bind because often they can avoid disparate impact only by engaging in unlawful disparate treatment (racial preferences). Some personnel psychologists have argued that there is scientific justification for race-based adjustments in test scores that eliminate disparate impact. Analyses of their seemingly scientific reasoning illustrate how personnel selection science is being compromised in an effort to reconcile contradictory legal demands. PMID- 7985886 TI - Within-group norming and other forms of score adjustment in preemployment testing. AB - Various forms of score adjustment have been suggested and used when mean differences by gender, race, or ethnicity are found using preemployment tests. This article examines the rationales for score adjustment and describes and compares different forms of score adjustment, including within-group norming, bonus points, separate cutoffs, and banding. It reviews the legal environment for personnel selection and the circumstances leading to the passage of the Civil Rights Act of 1991. It examines score adjustment in the use of cognitive ability tests, personality inventories, interest inventories, scored biographical data, and physical ability tests and outlines the implications for testing practice of various interpretations of the Civil Rights Act of 1991. PMID- 7985888 TI - Neuroticism and the illusion of mental health. PMID- 7985889 TI - "Illusion" of mental health does not explain positive illusions. PMID- 7985890 TI - Levothyroxine and potassium iodide are both effective in treating benign solitary solid cold nodules of the thyroid. AB - OBJECTIVE: To determine the effectiveness of levothyroxine and potassium iodide in treating patients with benign solitary cold thyroid nodules. DESIGN: Randomized controlled study. SETTING: Outpatient clinic at a university hospital. PATIENTS: 80 patients with solitary solid cold thyroid nodules found to be benign at cytologic examination were randomly assigned to no treatment, suppressive levothyroxine (thyroid-stimulating hormone level, < 0.3 mU/L), or low-dose potassium iodide (2 mg every 2 weeks). Seventy patients completed the 1-year study. After 1 year, patients receiving treatment discontinued drug therapy and were re-evaluated 4 months later; patients receiving no treatment were given levothyroxine and were followed for a second year. MEASUREMENTS: Nodule volume was measured by ultrasonography at 4-month intervals by an observer masked to treatment assignment. RESULTS: Mean nodule volume decreased by 40% of the basal volume in the 23 patients receiving levothyroxine (P < 0.001) and by 23% of the basal volume in the 25 patients receiving potassium iodide (P = 0.053). Volume slightly increased in the 22 untreated patients (P = 0.085). A clinically relevant reduction in nodule volume (> or = 50%) was observed in 9 of 23 patients treated with levothyroxine, in 5 of 25 patients treated with potassium iodide, and in none of 22 untreated patients (P = 0.004). Only nodules with a volume of 10 mL or less were reduced; nodules with volumes of 5 mL or less shrank most frequently. Nodule volume did not relevantly increase in treated patients but did increase in 3 of the 22 untreated patients. Drug withdrawal resulted in an increased mean nodule volume (P = 0.004) after 4 months. CONCLUSIONS: Levothyroxine and, to a lesser extent, potassium iodide are effective in arresting the growth or in reducing the volume of benign solitary solid cold thyroid nodules, especially small ones; discontinuation of therapy may result in resumed nodule growth. PMID- 7985891 TI - Type III procollagen peptide in the adult respiratory distress syndrome. Association of increased peptide levels in bronchoalveolar lavage fluid with increased risk for death. AB - OBJECTIVE: To determine whether bronchoalveolar lavage fluid levels of the N terminal peptide of type III procollagen (procollagen III) are increased in patients with the adult respiratory distress syndrome and, if so, whether increased procollagen III levels in lavage fluid are associated with increased fatality rates. DESIGN: Prospective cohort study. SETTING: Intensive care units of a tertiary care hospital affiliated with a medical school. PATIENTS: 117 consecutive patients with the adult respiratory distress syndrome prospectively identified on admission; 6 healthy volunteers served as controls. MEASUREMENTS: Bronchoalveolar lavage fluid procollagen III levels in 117 patients at 3, 7, and 14 days after onset of the adult respiratory distress syndrome (total of 196 lavage samples). RESULTS: The median procollagen III level was 1.75 U/mL (range, 0 to 13.4 U/mL) in lavage fluid obtained from patients with the adult respiratory distress syndrome. We detected procollagen III levels in lavage fluid from 80% of patients (94 of 117) but not in 6 normal volunteers. The overall fatality rate was 41% (48 of 117 patients). In a univariate analysis, the relative risk (RR) for death was increased in patients with procollagen III levels of 1.75 U/mL or more obtained on day 3 (RR, 2.4; 95% CI, 1.3 to 4.3), day 7 (RR, 2.7; CI, 1.4 to 5.4), and day 14 (RR, 2.7; CI, 1.1 to 6.3). Inclusion of other variables in a multivariate model only minimally decreased the risk associated with increased procollagen III levels. CONCLUSION: Increased levels of type III procollagen in bronchoalveolar lavage fluid are frequently detected in patients with the adult respiratory distress syndrome and are strongly associated with increased risk for fatal outcome independent of other variables related to fatality in patients with the syndrome. PMID- 7985892 TI - Combination and monotherapy with zidovudine and zalcitabine in patients with advanced HIV disease. The NIAID AIDS Clinical Trials Group. AB - OBJECTIVE: To compare the safety and efficacy of continuing zidovudine therapy with that of zalcitabine alone or zalcitabine and zidovudine used together. DESIGN: A randomized, double-blind, controlled trial. SETTING: AIDS Clinical Trials units and National Hemophilia Foundation sites. PATIENTS: 1001 patients with symptomatic human immunodeficiency (HIV) disease and 300 or fewer CD4 cells/mm3 or asymptomatic HIV disease and 200 or fewer CD4 cells/mm3 who had tolerated zidovudine therapy for 6 months or more. INTERVENTION: Patients were randomly assigned to receive zidovudine, 600 mg/d; zalcitabine, 2.25 mg/d; or zidovudine, 600 mg/d, and zalcitabine, 2.25 mg/d. MEASUREMENTS: The primary end point was time to disease progression or death. RESULTS: The median follow-up time was 17.7 months. The estimated 12-month event-free rates were 70%, 67%, and 73%, respectively, for the zidovudine, zalcitabine, and combination groups (P = 0.26). A trend analysis showed significantly lower progression rates for combination therapy compared with zidovudine therapy as the pretreatment CD4 cell count increased (P = 0.027). For patients with 150 or more CD4 cells/mm3, those receiving combination therapy were less likely to have disease progression or to die than were those receiving zidovudine (relative risk, 0.51; 95% CI, 0.28 to 0.93; P = 0.029). We observed no difference between the zalcitabine and zidovudine groups (relative risk, 0.74; CI, 0.40 to 1.36; P = 0.33). For patients with 50 to 150 CD4 cells/mm3 or fewer than 50 CD4 cells/mm3, we found no differences among the treatment groups (P = 0.69 and P = 0.57, respectively). Severe toxic effects occurred less frequently among patients with 150 or more CD4 cells/mm3. CONCLUSIONS: We found no overall benefits of zalcitabine used alone or with zidovudine. However, a trend analysis suggested a better outcome for combination therapy compared with zidovudine as the pretreatment CD4 cell count increased. PMID- 7985893 TI - Enzyme therapy in type 1 Gaucher disease: comparative efficacy of mannose terminated glucocerebrosidase from natural and recombinant sources. AB - OBJECTIVE: To compare the efficacy of mannose-terminated glucocerbrosidase prepared from natural (alglucerase; Ceredase, Genzyme Corp., Cambridge, Massachusetts) and recombinant (imiglucerase; Cerezyme, Genzyme Corp.) sources in treating type 1 Gaucher disease. DESIGN: Double-blind, randomized, parallel trial. SETTING: University medical center and clinical research hospital. PATIENTS: 15 patients (4 children and 11 adults) randomly assigned to receive Ceredase and 15 patients (3 children and 12 adults) assigned to receive Cerezyme. INTERVENTION: Ceredase and Cerezyme were infused every 2 weeks for 9 months at a dose of 60 U/kg body weight. OUTCOME MEASURES: Hemoglobin levels, platelet counts, and serum acid phosphatase and angiotensin-converting enzyme activities were monitored every 2 weeks during the trial. Hepatic and splenic volumes were assessed at the time of randomization and after 6 and 9 months of enzyme infusion. Formation of IgG antibodies to Ceredase or Cerezyme was monitored every 3 months by radioimmunoprecipitation assay. RESULTS: No significant differences were found in the rate or extent of improvement in hemoglobin levels, platelet counts, serum acid phosphatase or angiotensin-converting enzyme activities, or hepatic or splenic volumes between either treatment group. The incidence of IgG antibody formation was greater in the Ceredase group (40%) than in the Cerezyme group (20%). No major immunologic adverse events occurred in either group. CONCLUSIONS: Our study shows the therapeutic similarity of Ceredase and Cerezyme. Cerezyme has the advantage of being theoretically unlimited in supply and free of potential pathogenic contaminants. PMID- 7985894 TI - Temporary discontinuation of warfarin therapy: changes in the international normalized ratio. AB - OBJECTIVE: To measure the rate of decrease of the international normalized ratio (INR) after temporary discontinuation of warfarin therapy. DESIGN: Prospective evaluation of an outpatient cohort. SETTING: University medical center anticoagulation clinic. PATIENTS: 22 patients receiving a fixed evening dose of warfarin for whom temporary discontinuation of therapy was deemed safe. MEASUREMENTS: Serial plasma samples were drawn for INR measurements approximately 20, 65, 115, and 185 hours after patients received the last dose of warfarin. In five patients, INR was measured twice daily for 5 days. RESULTS: For patients with a mean steady-state INR of 2.6, the mean INR 65 hours (2.7 days) after discontinuation of warfarin therapy was 1.6 (range, 1.11 to 2.16); 20 of 22 patients (91%) had an INR greater than 1.2. The mean INR 115 hours (4.7 days) after discontinuation of warfarin therapy was 1.1; 5 of 22 patients (23%) had an INR of 1.2 or greater. In 5 patients studied in detail, the INR decreased exponentially and had a half-life that ranged from 0.52 to 1.2 days; the onset of maximal decrease began 24 to 36 hours after discontinuation of warfarin therapy. In the total cohort, age was a significant (P < 0.005) independent predictor of smaller decreases in the INR between day 1 and day 3 (regression coefficient = 6.8% +/- 2%/2 days per decade of age; R2 = 0.34). CONCLUSIONS: By simulating preoperative discontinuation of warfarin therapy, we found that the INR decreases exponentially, with wide interpatient variation in the rate of decrease. Age is associated with a slower rate of decrease. To be certain that the INR at the time of the surgery is less than 1.2, warfarin should be withheld for 96 to 115 hours (4 doses) in patients with a steady-state INR between 2.0 and 3.0. For patients with a higher steady-state INR, a longer wait is necessary. PMID- 7985895 TI - Allergy to latex rubber. AB - OBJECTIVE: To summarize the clinical symptoms of latex rubber allergy and provide guidelines for the management of this allergy. DATA SOURCES: The English-language literature was searched from 1979 through 1994 manually and using MEDLINE. Conference proceedings and reference lists of relevant articles were reviewed. DATA EXTRACTION: Studies clinically relevant to latex allergy were selected. RESULTS: The most common clinical presentation of latex allergy is a nonimmunologic, irritant dermatitis of the hand. Contact dermatitis (type IV delayed hypersensitivity reactions to rubber additives) is the most common immunologic manifestation of latex rubber allergy. Type I allergic responses are less common and include contact urticaria, rhinoconjunctivitis, asthma, and anaphylaxis. Seven percent to 10% of health care workers regularly exposed to latex and 28% to 67% of children with spina bifida have a positive skin test result to latex proteins indicating increased blood levels of IgE antibody. About one third of patients with positive skin test results, however, do not yet have symptoms of latex allergy. Systemic (life-threatening) anaphylactic shock can occur intraoperatively in highly sensitive patients because of mucosal absorption of latex protein allergens from the surgeon's gloves. The present treatment for latex allergy is careful avoidance of latex materials. In addition, the use of powder-free latex gloves can eliminate airborne latex exposure and can allow health care workers with inhalant allergic reactions to return to work. CONCLUSION: Latex allergy currently affects thousands of people. These persons have IgE-mediated cutaneous, respiratory, and systemic allergic reactions. A reduction of the total protein level on latex rubber devices may prevent further sensitization and eliminate latex allergic reactions. PMID- 7985896 TI - Accuracy of ultrasound for the diagnosis of deep venous thrombosis in asymptomatic patients after orthopedic surgery. A meta-analysis. AB - OBJECTIVE: To evaluate, by meta-analysis, the accuracy of ultrasound screening for deep venous thrombosis in patients after orthopedic surgery. DATA SOURCES: The MEDLINE database from January 1982 to October 1993. Bibliographies of retrieved articles and recent journal publications were searched independently and using Current Contents. STUDY SELECTION: All articles evaluating the use of venous ultrasound imaging (B-mode, duplex, and color Doppler) compared with standard contrast venography for detecting deep venous thrombosis. We excluded abstracts, early reports of studies later reported in full, and studies in which venography was not done in all patients. Seventeen of 30 identified studies were eligible. DATA EXTRACTION: Eligible articles were reviewed for the presence of three key criteria necessary for evaluating the accuracy of the diagnostic tests: 1) previously established objective criteria for venography and ultrasound, 2) independent blinded comparisons of venography and ultrasound, and 3) prospective evaluations of consecutive patients. Studies including all three key criteria were defined as level 1 (minimized bias) studies; otherwise, they were defined as level 2 studies. DATA SYNTHESIS: In level 1 studies, ultrasonography had a sensitivity of 62% (95 of 153; 95% CI, 54% to 70%), a specificity of 97% (CI, 96% to 98%), and a positive predictive value of 66% (95 of 144; CI, 58% to 74%) for detecting proximal thrombi. For level 2 studies, the sensitivity was 95% (CI, 87% to 99%), the specificity was 100% (CI, 99% to 100%), and the positive predictive value was 100% (CI, 94% to 100%). Differences between level 1 and level 2 studies appeared to be related to bias in study design. CONCLUSIONS: Venous ultrasound imaging has only moderate sensitivity and a moderate positive predictive value when used to screen for deep venous thrombosis in patients after orthopedic surgery; thus, ultrasound imaging may have limitations as a screening test. PMID- 7985897 TI - Modulation of collagen gene expression: its relation to fibrosis in systemic sclerosis and other disorders. AB - Fibrosis is the pathologic hallmark of many common diseases. Much information has recently emerged about the cellular and biochemical events that result in its development and progression. It is now known that in affected tissues, chronic inflammation generally precedes fibrosis and that inflammatory cell-derived cytokines are crucial mediators of fibrogenesis. Several cytokines have been identified that influence wound healing and tissue repair processes in vivo and that modulate the production of collagen in vitro. Of these, transforming growth factor-beta is of the most interest because this pleiotropic cytokine is expressed at high levels during tissue remodeling and greatly affects the formation of connective tissue. Furthermore, it has been recently shown that transforming growth factor-beta can stimulate the transcription of collagen genes through the production or activation of specific DNA-binding trans-acting factors. A precise understanding of the molecular mechanisms responsible for the effects of this cytokine on collagen gene expression may allow the design of selective therapeutic interventions aimed at retarding or preventing the development of fibrosis. PMID- 7985898 TI - Why do clinicians continue to debate the use of levothyroxine in the diagnosis and management of thyroid nodules? PMID- 7985899 TI - Fibrosing alveolitis in the adult respiratory distress syndrome. PMID- 7985900 TI - Restriction isotyping of apolipoprotein E. PMID- 7985902 TI - Clinical use of apolipoprotein quantitation. PMID- 7985901 TI - Clinical use of apolipoprotein quantitation. PMID- 7985903 TI - Clinical use of apolipoprotein quantitation. PMID- 7985904 TI - Respirators and tuberculosis. PMID- 7985905 TI - Respirators and tuberculosis. PMID- 7985906 TI - Cutaneous alternariosis after renal transplantation. PMID- 7985907 TI - Collagenous colitis and systemic lupus erythematosus. PMID- 7985908 TI - Training general internists and "STARS". PMID- 7985909 TI - Training general internists and "STARS". PMID- 7985910 TI - Training general internists and "STARS". PMID- 7985911 TI - In-training examination in internal medicine. PMID- 7985912 TI - In-training examination in internal medicine. PMID- 7985913 TI - In-training examination in internal medicine. PMID- 7985914 TI - Estrogen replacement therapy and fractures in older women. Study of Osteoporotic Fractures Research Group. AB - OBJECTIVE: To determine the relation between estrogen replacement therapy and fractures. DESIGN: Prospective cohort study. SETTING: Four clinical centers in Baltimore County, Maryland; Minneapolis, Minnesota; Portland, Oregon; and the Monongahela Valley, Pennsylvania. PARTICIPANTS: 9704 ambulatory, nonblack women 65 years of age or older. MEASUREMENTS: Estrogen use, medical history, and anthropometric data were obtained by questionnaire, interview, and examination. Appendicular bone mass was measured by single-photon absorptiometry. Incident fractures were validated by radiographic report. RESULTS: After adjustment for potential confounders, current estrogen use was associated with a decrease in the risk for wrist fractures (relative risk [RR], 0.39; 95% CI, 0.24 to 0.64) and for all nonspinal fractures (RR, 0.66; CI, 0.54 to 0.80) when compared with no estrogen use. Results were similar for women using unopposed estrogen or estrogen plus progestin, for women younger or older than 75 years of age, and for current smokers or nonsmokers. The effect of estrogen remained after adjustment was made for appendicular bone mass. The relative risk for hip fracture tended to be lower among current users (RR, 0.60; CI, 0.36 to 1.02) than among never-users. Estrogen was most effective in preventing hip fracture among those older than 75 years. Current users who started estrogen within 5 years of menopause had a decreased risk for hip fractures (RR, 0.29; CI, 0.09 to 0.92), wrist fractures (RR, 0.29; CI, 0.13 to 0.68), and all nonspinal fractures (RR, 0.50; CI, 0.36 to 0.70) when compared with women who had never used estrogen. Previous use of estrogen for more than 10 years or use begun soon after menopause had no substantial effect on the risk for fractures. CONCLUSIONS: Current use of estrogen appears to decrease the risk for fracture in older women. These results suggest that for protection against fractures, estrogen should be initiated soon after menopause and continued indefinitely. PMID- 7985915 TI - Chronobiology: principles and methods. AB - Chronobiology is a discipline whose principles consider time as an essential dimension of biological phenomena. The reason of this resides in a relativistic vision of biological dynamism for which space, mass, energy and time are properties of dynamic events. Biological time may be linear (chronological time) and cyclical (period time). Chronobiology considers the biological events whose expression is periodic with several kinds of periodicities (biological rhythms). Because of bioperiodic events, a methodology for approaching cycling functions is needed. Chronobiometry is illustrated as an important part for understanding how biological rhythms can be investigated. PMID- 7985916 TI - Chronobiology: neural pacemakers of biological rhythms. AB - Biological rhythms are ubiquitous being demonstrable of any level of organization in living matter. However, the myriad of biological oscillators in peripheral organs are organized and synchronized by special structure, i.e., biological clocks, mostly located in central nervous system. Neural pacemakers show intrinsic properties which are illustrated and discussed. Understanding the meaning and function of neural oscillators is fundamental for those who wants to know how the biological structure of time is processed in living systems. PMID- 7985917 TI - A feeding-entrainable circadian oscillator system in the rabbit. AB - One of the most important properties of biological oscillators is their entrainment by exogenous forces acting cyclically in the environment. Among the environmental cycles, the phenomena recurring with a circadian periodicity are very prominent. The role of circadian zeitgebers is discussed giving a particular importance to the effects of feeding as a cause of masking and entrainment. PMID- 7985918 TI - Historical comments on chronobiology with emphasis on cell proliferation, the concept of free running, cancer chemotherapy and experimental design. AB - A brief historical summary is presented regarding the emergence, over the past several decades, of chronobiology as the newest of the integrating discipline of biology. The emphasis is on the circadian system which normally is synchronized to the 24 h environmental light-dark cycle. In the absence of a suitable synchronizer, the system free runs on its own endogenous genetically determined frequency, which usually only approximates 24 h. Since the metabolic system changes rhythmically in time it follows that an organism such as man is biochemically and physiologically a different entity at different circadian stages; therefore it reacts differently to an identical stimulus given at different times. Different stimuli such as anticancer agents are examples considered clearly timed treatment has been shown to significantly improve therapeutic efficacy, data will be presented using the L1210 mouse leukemic model. Moreover data is presented showing that to ignore such rhythmic fluctuation when designing experiments that such can bring about experimental error and false interpretation. The common "same time of day" sampling does not take care of the rhythmic problem! PMID- 7985919 TI - Time and body chemistry: questions and answers. AB - This is an article based on questions and answers which are aimed at explaining of chronobiological principles from rhythms of chemical compounds of living matter. The chemical aspect of biological rhythms is important considering that any biological event is guided by chemical phenomena. The dialogue helps us to understand how biochemical rhythmicities are fundamental for clinical health, their deviations being demonstrable in pathophysiological conditions. PMID- 7985920 TI - Reactive modifications of the autonomous time structure of biological functions in man. AB - The spectrum of biological rhythms exhibits characteristic principles of biological time structure which also rule the functional behaviour. With increasing period lengths the rhythms become increasingly complex. In the long wave section the rhythmic functions find their corresponding cycles in the environment, whereas the shorter waves represent only endogenous autonomous rhythms, which maintain an internal time order by means of frequency- and phase coordination. Under resting conditions and in a state of complete adaptation only a few spontaneous rhythms dominate in the spectrum. However, under loading conditions as well as in pathological situations further periodicities come up. The spectrum of rhythms can be divided into certain blocks, with the period lengths predominating in each of these whole number frequency ratios forming a harmonic system. Frequency- and phase-coordination establish a system of co action which favours the functional economy of the organism. A tripartite organization of the autonomous rhythms involves different functional behaviours with regard to frequency, amplitude, and phase. Slower rhythms act upon the faster rhythms preferably by modulating their frequencies, while changes of the faster rhythms influence the slower ones by enhancing their amplitudes, multiplying their period lengths and shifting their phases. In principle the reactions of living systems are periodically structured. Reactive periodicity brings to appearance an endogenous time structure, which prefers whole number relationships with the spontaneous rhythms. The phase position of reactive periods depends on the stimulus. The amplitudes dampen down with increasing compensation. From the medical point of view so-called circaseptan (about 7 days) reactive periods are of predominant interest. This periodicity can be observed in numerous adaptive and compensating processes. It does not depend on the external week cycle and was already known to the antiquity. PMID- 7985921 TI - Chronobiology in epidemiology and preventive medicine. AB - Many of the known cardiovascular risk factors, such as hormones, metabolic parameters, lifestyle, blood pressure, fibrinogenesis, fibrinolytic activity, etc., and also the reactivity of the organism to stimuli, are periodical and therefore require adequate measures at specific times in appropriate frequencies. The presence of circadian, circannual or other wide frequency rhythms may lead to contradiction in the evaluation of a potential risk factor. Chronobiological analysis shows fine differences within a "risk variable", defining some characters which may imply the alteration of a parameter only at certain times. Periodical risk factors may therefore be foreseen and sometimes prevented. Moreover, chronobiological approach may show another peculiar relation between risk factors; this is the so-called chronorisk. The convergence, in certain periods of time, of the phases of various risk factors, may strengthen their combined value. On the other hand, the phases of the protective factors, in the same period of time, may contribute to reduce or strengthen this combined value. From this point of view combined risk, apparently unimportant, appears highly increased, as compared with the normal homeostatic value. At equal levels of risk factors, different distribution and amplitude of the phases implies great differences in final combined risk values. Acute heart attack has a daily, seasonal and perhaps ultradian rhythm; other cardiological events, such as angina pectoris and sudden death, have circadian rhythms. Also cerebral vascular events have daily, seasonal, weekly and monthly variations. The periodical variations of acute vascular events and of the related risk factors, near and far, implies many complex interrelations in timing of biological structures, which are still perceived by the physician only as "noise". PMID- 7985922 TI - Chronoepidemiology in human diseases. AB - Current knowledges about time-dependent variations in onset of several acute medical diseases are briefly reviewed. Moreover, temporal variation in relative risk factors are also discussed. Any clue to the increased likelihood of a given event can heighten suspicion and shorten time of effective action. The predictability of a certain event, due to the periodicity of cyclic changes, can be of a practical interest in everyday medical practice. PMID- 7985923 TI - Chronobiology in laboratory medicine. AB - A critical amount of information has accumulated over the last decades to allow the application of chronobiology to clinical and laboratory medicine. The tasks faced in laboratory medicine include the quantitative measurement of the multifrequency human time structure in health and disease. For this purpose, it is essential to choose an adequate sample size in order to obtain meaningful results and quantitative endpoints which can be interpreted by inferential statistical techniques. No statistical technique is applicable for all purposes and it is essential that the assumptions underlying each technique and its limitation are well known to the investigator. The multifrequency nature of the human time structure has to be kept in mind in order to avoid erroneous results. Time qualified reference ranges have to be established for high amplitude rhythms. Circadian and/or circannual rhythm alterations have been described as group phenomenon in subjects with epidemiologically determined risk states for common diseases, but will require much further studies for the application to individual subjects. Rhythm parameters are new endpoints in the evaluation of the human time structure in health. Alterations of these parameters may occur as cause or as consequence of disease. Recognition of rhythm abnormalities in disease are critical for a meaningful application of chronopharmacology. Time dependent changes in pharmacokinetics and pharmacodynamics have to be taken into account in the interpretation of drug level determinations. A considerable degree of individuality of timing has been documented in some frequencies. This individuality and the rhythm abnormalities found in disease require the study of reference or marker rhythms. If the complexity of the human time structure is clearly understood and its study pursued in a critical manner with quantitative endpoints, chronobiology opens a new dimension in laboratory and clinical medicine. PMID- 7985924 TI - Saliva as a medium for chronobiological studies: its particular potential in steroid endocrinology. AB - This paper indicates the potential of saliva as a medium for chronobiological studies. It has principally focussed on the work of the Tenovus Institute for Cancer Research, at the University of Wales College of Medicine over the past decade or more, particularly for steroid hormones, so as to give an authoritative viewpoint based on practical experience. The article discusses issues ranging from technical to clinical aspects of hormone assay in saliva, showing disadvantages and limitations of use. Increasingly, many other investigators are developing and applying assays for salivary steroids and it is timely that such assays become tools in the hands of the chronobiologist. The clinical-biochemical importance of saliva resides also in the fact that in its context it is possible to assay enzymes, toxic substances and drugs. PMID- 7985925 TI - Chronobiology in endocrinology. AB - Temporal endocrine structure (TES). It can be defined as a combination of predictable hormonal changes that are time-related. Regarding their frequency, endocrine rhythms may be circadian, ultradian and infradian. In this context, the endocrine circadian time structure (ECTS), that is closely dependent of some areas of the hypothalamus, is of particular interest. Long and short loop feedback link together the various components: central nervous system (CNS), hypothalamus and anterior pituitary with target glands and tissues. The hypothalamic neuropeptides (releasing hormones or factors - RH or RF - or inhibiting hormones or factors IH or IF) presently known are: thyrotropin releasing hormone (TRH); luteinizing releasing hormone (LH RH); prolactin releasing factor (PRF); Prolactin Inhibiting Factor (PIF); Corticotropin Releasing Factor (CRF); Growth Releasing hormone (GH RH). Some general remarks on endocrine rhythms should be noted: the circadian changes in hormones may depend on each other; even an apparently subordinate rhythm should be considered a true independent rhythm; accurate studies have shown that hormonal secretion occurs in all cases according to a rhythmic organization at many levels; these rhythms may not be evident at a first analysis. The hormone secretion is basically pulsating which makes it difficult to draw standard reference values. Although an ECTS is present at the cell level, in organs etc., it is evident that a rhythm hierarchy exists. Hormonal secretion and sleep-wake cycle. Although several reports state that no rhythm is totally dependent on the sleep-wake cycle, from a general point of view the hormone secretion rhythms can be divided in: sleep-dependent rhythms and sleep-independent rhythms. Meal-timing and hormonal secretion. In animals, meal-timing is a powerful synchronizer; however, there are no definitive and conclusive data to prove that meal-timing is a true synchronizer also in humans, although there have been some reports suggesting it. Endocrine rhythms. Data regarding the endocrine rhythms (circadian-ultradian-infradian) of the numerous hormones as GH; prolactin; aspects of temporal pattern of CRF-ACTH-corticosteroid and of hypothalamic - pituitary - thyroids axis; hypothalamic - pituitary - ovaric steroid and testosterone axis are reported. The study of a possible rhythmic pattern of insulin has been approached from many points of view as the basal rhythmicity of insulin; the diurnal variation of efficacy of injected insulin and of insulin responsiveness to insulinogenic stimuli. PMID- 7985926 TI - Chronobiology in cardiology. AB - In these years, circadian periodicity in the onset of myocardial ischemia, myocardial infarction, sudden cardiac death and ischemic stroke has been confirmed by several investigators. There has also been reported that there exists a significant circadian rhythm in ventricular arrhythmias in patients with myocardial infarction. These recent advances in chronocardiology depend on a development of a high quality built-in A/D converter in ambulatory ECG monitoring system and a remarkably developed sophisticated software. One of the most current topics in recent years is heart rate (HR) variability. As an index of HR variability, RR50 is frequently estimated by the cosine fitting technique. Next, we analyzed the so-called Lorenz plot for another index of HR variability, that is preceding R-R intervals and coupling intervals were plotted sequentially every 3 hours on the abscissa and ordinate, respectively. Finally, we investigated HR variability by power spectral analysis of R-R intervals both by the maximum entropy method and the fast Fourier transform. Mainly, in this paper, we introduced current topics in HR variability, but recent advances in ambulatory blood pressure (BP) monitoring system are also strikingly remarkable. Our newly developed monitoring system of physical activity donated quite a few informations evaluating episodic changes of HR and BP. This device was also useful for finding out the difference between the individual life styles, such as the eveningness versus morningness. In conclusion, these very recent advances in ambulatory monitoring system should be really available for the clinical practice from this time onward. PMID- 7985928 TI - Blood pressure rhythms and salt. PMID- 7985927 TI - Rhythms and blood pressure. AB - The time (chronos) structure of life (bios) is the topic of a computer implemented science (logos), chronobiology. Chronobiologic methods for resolving physiologic time structure provide a more reliable mean, the MESOR, and other parametric dynamic measures of blood pressure variability. The amplitude is a measure of predictable extent of change and the acrophase a measure of timing of overall high values within each cycle of the rhythmic function. Such chronobiologic endpoints are often more sensitive than the mean for separating groups at different risk of developing high blood pressure. About 24-h (circadian) rhythms account for a sizeable part of predictable variability in blood pressure. Methodology to assess the characteristics of circadian blood pressure rhythms also provides time-varying reference limits for the interpretation of single measurements. Deviant blood pressures can be quantified by reference to such circadian-stage-dependent limits, derived from the automatically monitored blood pressure profiles of healthy peer groups. Excess or deficit in blood pressure can also be assessed as a hypertensive or hypotensive index integrated over 24 h. Chronobiologic monitoring has wide uses in practice as well as research, whether it is carried out by self- or automatic measurements, once the data are analyzed by appropriate computer methods that are now readily available. PMID- 7985929 TI - Chronobiology approach to human hypertension. AB - The present article is aimed to make the status of the art on the diagnosis of hypertension using the non-invasive automated devices for measuring blood pressure (BP) over the 24 h span. The diagnostic procedure is based on specific criteria eminently devoted to the temporal evaluation of the BP 24 h pattern in its variability, either discrete or periodic. The procedure, called "chronodiagnosis of hypertension", is articulated in three procedural levels, each corresponding to a particular chronobiometry of the BP 24 h pattern. The chronodiagnostic procedure is detailed step by step. PMID- 7985930 TI - Chronobiologic assessment of antihypertensive therapy. AB - This paper is an example of the clinical application of chronobiologic methods to the diagnosis of the major killers of modern societies, i.e., hypertension. Passing from the description of the methodology to clinical examples, the article provides convincing evidence of the importance of the chronodiagnostic approach to ambulatory blood pressure monitoring not only for a more accurate diagnosis, but also for a more appropriate therapy. PMID- 7985932 TI - [Mechanisms of autoimmunity]. PMID- 7985931 TI - Circadian cancer pharmacodynamics. AB - After a large recognition of experiments and concepts developed in the centuries on the pharmacological treatment of human diseases, the article concisely provides the state of the art on chronotherapy of cancer. The techniques and results are illustrated. The perspectives of optimizing cancer therapy via optimal circadian schemes of pharmacological agents are clearly suggested. PMID- 7985933 TI - Combined use of plasma exchange and intravenous immunoglobulins. PMID- 7985934 TI - The Guillain-Barre syndrome: plasma exchange or immunoglobulins intravenously? PMID- 7985935 TI - Plasmapheresis and subsequent pulse cyclophosphamide in severe systemic lupus erythematosus. An interim report of the Lupus Plasmapheresis Study Group. AB - The rarity with which therapy-free remission is achieved in patients with severe SLE demand the continued search for improved treatment strategies. Possibly, therapeutic results can be improved by means of a "synchronized" combination of plasmaphereses followed by pulse cyclophosphamide (Ctx). If the hypothesis is correct, that plasmapheresis induces a compensatory "rebound" proliferation of pathogenic clones, then pulse Ctx applied immediately after plasmapheresis should attack these activated clones when they are most vulnerable and, ideally, eliminate them. Employing a strict variant of this strategy in a pilot study, treatment-free remission lasting now for up to 7 years were achievable in 8 of 14 SLE patients. The Lupus Plasmapheresis Study Group (LPSG) is currently conducting a randomized international multicenter trial comparing a synchronized procedure with the administration of pulse Ctx alone. The present paper explains the rationale of synchronization and reports on the interim status of the LPSG Study. PMID- 7985936 TI - Elimination of an artificial immune complex by plasmapheresis in rabbits. AB - The behaviour of an artificial immune complex was investigated in 15 rabbits. The immune complex was labelled with iodine-125 (125I). The advantage was that the immune complex could not be metabolized without being eliminated by the kidney. This artificial immune complex was injected in different dosages (0.8 micrograms 40 micrograms/rabbit) on 2 consecutive days. One group (n = 9) was treated with plasmapheresis: the other (n = 6) was a control group that did not undergo plasmapheresis. A miniaturized plasmapheresis system eliminated the immune complex very effectively. The increasing concentration of the immune complex in the blood before the next plasmapheresis treatment was probably an expression of mobilization of the immune complex from different organs. The animals of the plasmapheresis group were in better condition than the control group. PMID- 7985937 TI - Therapy of lupus nephritis. A two-year prospective study. AB - The aim of our study was to compare the efficacy of 3 different therapeutic protocols in the treatment of patients with WHO class IV lupus nephritis and normal renal function. We carried out a randomized prospective trial. The treatment programs consisted of a standard therapy regimen alone (protocol A), plus plasmapheresis (protocol B) or pulse methylprednisolone (protocol C), followed by a slow (protocols A and B) or fast (protocol C) prednisone tapering schedule. Statistical analysis was performed, using univariate survival analysis according to Kaplan Meier and Breslow's test to compare survival curves. Eighteen patients entered the study: 6 protocol A, 5 protocol B and 7 protocol C. No patients developed renal insufficiency. Moreover, no statistical differences in the probability of inducing partial or complete disease remission and in reducing 24-hour urinary protein excretion to < or = 2 g per day were observed among the groups. Protocols A and B were more effective in comparison with protocol C in decreasing 24-hour urinary protein excretion to < or = 0.5 g and < or = 0.2 g per day. In conclusion, a slow prednisone tapering schedule is more effective in reducing 24-hour urinary protein excretion to < or = 0.5 and < or = 0.2 g per day as compared with a fast prednisone tapering schedule, even if it is preceded by methylprednisolone pulse therapy. PMID- 7985938 TI - [Treatment of organ graft rejection by extracorporeal photochemotherapy]. AB - Extracorporeal photochemotherapy is a recently developed immunomodulator treatment against heart and lung graft rejection. The recipient's mononuclear cells are screened and irradiated with UV-A in the presence of 8-methoxy psoralene (8-MOP), then reinjected. We treated 4 patients who had begun to reject their heart and/or lung grafts, with this technique, using one session per week for 4 weeks, followed by one session every 2 weeks for 2 months, then one session per month. In all cases, extracorporeal photochemotherapy appeared to improve the clinical and biological status of these patients. Episodes of rejection which could not be reversed with immunosuppressor treatment alone were controlled. PMID- 7985939 TI - [Fundamental bases for the use of immunoadsorption. Its value among hemapheresis techniques]. PMID- 7985940 TI - [Technological development of plasma epuration: treatment of the plasma]. PMID- 7985941 TI - [Immunoadsorption of anti-HLA antibodies on protein A-sepharose columns in hyperimmunized recipients waiting for transplantation]. AB - In an attempt to reduce anti-HLA immunization in 15 patients awaiting for renal grafts and who were immunized against 65% of a panel of lymphocytes (titre 1/8 to 1/128), were given 5 to 7 sessions of immunoadsorption on protein A columns, immunosuppressor drugs (corticosteroids: 1 mg/kg/day + cyclophosphamid: 2 mg/kg/day) and intravenous polyclonal immunoglobulins. The antibody titres decreased in all patients, but this protocol did not sufficiently block resynthesis of antibodies. Among the 12 patients who were transplanted, the graft functioned correctly in 8 after a follow-up of 3 months to 3 years. Three early graft failures occurred in the group of 5 patients whose had had a positive cross match before treatment. This treatment did not appear to increase the frequency of infectious complications immediately after transplantation. PMID- 7985942 TI - [Biological efficacy of LDL apheresis in major hypercholesterolemia]. AB - Severe hypercholesterolaemia include familial homozygous hypercholesterolaemia and certain heterozygous hypercholesterolaemias which become severe, due to spontaneous non-response to treatment or to iatrogenic side effects. Other causes include an associated overload in Lp(a) or uncontrolled atheromatous disease. Surgical treatment has been replaced by iterative LDL apheresis in these severe forms. Mean cholesterol and LDL cholesterol levels can be reduced by 41 to 63% and 49 to 68% respectively with LDL apheresis. In general, HDL cholesterol is protected in selective LDL apheresis. We observed similar decrease for apo B and LDL cholesterol levels. Fifty percent of the Lp(a) was removed in the 3 groups of patients studied. PMID- 7985943 TI - [Influence of the primary membrane on lipid apheresis selectivity in cascade filtration]. AB - In apheresis, plasma separation from whole blood may be achieved by filtration. Some plasmapheresis membranes do not seem to be totally permeable to proteins: for instance, polyvinyl alcohol membrane presents apparent sieving coefficients significantly lower than 1, especially for apolipoproteins B (S' = 0.74 +/- 0.15). Moreover, severe membrane fouling is noticed during the treatment. The low permeability of the primary membrane for ApoB induces direct recirculation of this lipoprotein to the patient, without any chance of removal by the second membrane. In order to increase double filtration performance, it seems necessary to use plasmalfilters with a pore diameter of 0.5 microns. These filters are more permeable to plasma proteins and eliminate pathogenic protein better during the second stage of the process. PMID- 7985944 TI - Effects of LDL apheresis on coronary heart disease. PMID- 7985945 TI - Excel: a new frontier in haemapheresis. AB - Haemapheresis is moving towards new prospects. The growing interest in stem cell collection, the increasing demand of single donor platelet units lead to a definition of a "new concept" of cell separator which can offer higher performance, higher selectivity and higher yield in order to guarantee superior quality and pureness of the collected product, but also higher treatment speed and easier usage, for improving user patient donor acceptability and safety level. For these reasons Dideco has developed the new Excel, an extremely innovative automatic blood cell separator, which opens new frontiers in the Haemapheresis field. The main technical features are summarized as following: automatic buffy coat level control through a CCD (charged coupled device), double eccentric-plate separation chamber (1 plate for every procedure), multi-processor system management, advanced user interface through a touch screen display, automatic fluid balancing system through load cell transducers, high-tech ergonomic design. All these innovative technologies are permitting an extremely high performance level higher PLT yield and lower WBC contamination (> 5 x 10(11) PLT with < 5 x 10(6) WBC--double leukodepleted PLT unit easy recoverable), lower procedure time (60 min for one PLT unit, 120 min for 2 unit), higher product quality (lower PLT activation, higher PLT reliability, lower complement activation-C3a), lower ACD consumption (higher withdrawal flow rates are possible), completely automatic procedure management, higher safety level, friendly and guided usage, customized protocols through a complete programmability. All these features and results also offer new standards for the field of haemapheresis through a new generation cell separator: Dideco Excel. PMID- 7985946 TI - [Study of the platelet concentrate obtained with the MCS cell separator of the Society of Haemonetics]. AB - The purpose of this work is to propose several platelets MCS programs which could be included in Haemapheresis Units. In the near future, one of our target is to decrease the transfusion risk. To reach this goal, it is very important to decrease the production of standard platelet concentrates from blood units by replacing them with platelet concentrates. For this work, we used MCS monitor from Haemonetics, equipped with two pumps. We have tested the platelet procedures by the mean of three programs (2.61, 3.61, 4.11 whole blood processed). The results showed good platelet yield (3.55, 4.82 and 5.37 1.10(11) for each program) with good quality of platelets up to 3 days storage (aggregation, beta thromboglobulin release). The MCS machine could complete platelet apheresis systems and might in the future replace the classical standard platelet concentrates. PMID- 7985947 TI - [Platelet transfusions, refractory states, contribution of laboratories]. PMID- 7985948 TI - [Fundamental aspects of the binding of drugs to circulating proteins]. PMID- 7985949 TI - Treatment of drug-related diseases by plasma exchanges. PMID- 7985950 TI - [Erythrocyte aggregation in patients treated by plasma exchange or plasma administration]. AB - The kinetic (aggregation times) and rheological (dissociation threshold) parameters or erythrocyte aggregation were determined before and immediately after each plasma epuration, using a device based on the analysis of the back scattered light by a blood suspension. We used two techniques of plasma epuration: a) classical plasma exchange: 8 multiple myelomas, 6 Waldenstrom diseases, with 42 procedures tested; b) plasma treatment/cascade filtration: one Waldenstrom disease with 9 procedures tested and 37 procedures in one patient suffering from hypercholesterolemia. We have completed this study by checking the rheological parameters in 46 procedures applied in 6 patients with hypercholesterolemia. In these patients, we have used the Kaneka technique (dextran sulfate). The parameters studied were: primary (Ta) and final (Tf) aggregation times, total (gamma D) and partial (gamma S) dissociation parameters. In all cases, the results showed an important decrease of Ta and Tf (with good improvement) and an increase of dissociation parameters showing the efficacy of such therapies. Erythrocyte aggregation constitutes a good panel of parameters to appreciate abnormalities before and after plasma epuration. PMID- 7985951 TI - [Microangiopathic hemolytic anemia associated with cancers. Symptomatic treatment by plasma exchange]. AB - OBJECTIVE: To determine the interest of plasmapheresis in the management of cancer-associated microangiopathic haemolytic anaemia (MHA) not due to cancer treatment. MATERIAL AND METHODS: [corrected] National retrospective study using the file of the French Hemapheresis Society. RESULTS: We isolated 6 patients (5 men and a woman aged 32 to 69-year-old) who had prostatic (4 cases) or breast carcinomas or Hodgkin's disease. Diagnosis of cancer preceeded MHA in 3 patients (from 2 to 4 years). Bone or bone marrow metastases were demonstrated in 5 patients. The clinical presentation included anuria (4 cases), bleeding (4 cases), and laboratory findings were consistent with microangiopathic haemolysis and thrombopenia in all cases and intravascular coagulation (2 cases) and/or renal failure (4 cases). MHA symptomatic treatment included 4 to 10 courses of plasmapheresis, extra-renal epuration (4 patients), anticoagulation (4 patients) and/or antiagregant (3 cases), haemodialysis (4 cases) and vincristine (2 cases). Cancer treatment consisted of antitumoural chemotherapy (2 cases) and/or hormonotherapy (5 cases). In all cases, haemolysis, thrombopenia and intravascular coagulation were controlled within 30 days. MHA treatment was effective alone in 3 patients. No relapse were observed in 3 patients whereas the course of cancer continued in 2 patients. Two patients relapsed and died from MHA after 4 and 36 months. Two patients relapsed and died from MHA within a few months and 1 was lost to follow-up. CONCLUSION: Symptomatic treatment of cancer associated MHA including plasmapheresis may be useful while waiting for an aetiologic management of the tumour. PMID- 7985952 TI - A kidney biopsy is clearly mandatory to confirm the indication of plasma exchanges in adult haemolytic uraemic syndrome. AB - In case of haemolytic uraemic syndrome, it is not always possible to identify on a pure clinical basis the different kidney lesions responsible for the syndrome. We report a series of six cases without thrombotic microangiopathy, which emphasizes the need to perform a kidney biopsy as early as possible, so as to confirm the actual usefulness of plasma exchanges (PE) commonly carried out in emergency in every case of adult haemolytic uraemic syndrome. PATIENTS AND METHODS--Files of patients who were treated for haemolytic uraemic syndrome over the past 14 years were reviewed. Patients in whom thrombotic microangiopathy had been excluded by renal histology data were studied. Every patient was promptly treated with hypotensive drugs, so as to obtain blood pressure levels not exceeding 160-90 mmHg. Dialysis was performed in two patients. Daily PE with fresh frozen plasma were carried out in three patients as early as the first 24 hours after admission, and discontinued immediately after thrombotic microangiopathy could be excluded. RESULTS--All the patients met the usual criteria for diagnosis of haemolytic uraemic syndrome. Elevated liver enzymes were also found in the four cases of preeclampsia, consisting with diagnosis of severe HELLP syndrome. One case was associated with oestrogen therapy. Glomerular lesions were seen in four patients: slight endotheliosis in three cases of preeclampsia; marked lesions of IgA mesangial deposits in the patient who had been treated by contraceptive pill. Three patients had acute tubular necrosis and three had intense lesions of nephrosclerosis. Complete remission was obtained in every case of preeclampsia. Renal failure persisted in two cases (IgA glomerulopathy and one case of nephrosclerosis). DISCUSSION--The histological heterogeneity of haemolytic uraemic syndrome has been already well demonstrated. Typical lesions of thrombotic microangiopathy are usually classified into predominant glomerular lesions, pure arteriolar and mixed lesions. In other cases, thrombotic microangiopathy is not found: kidney lesions may be glomerular (endotheliosis, various subtypes of glomerulonephritis), tubular (acute tubular necrosis) or vascular (nephroangiosclerosis). In every aetiological circumstance, several different lesions may be found together. The usefulness of PE has been proved in thrombotic thrombocytopenic purpura, has been suggested in haemolytic uraemic syndrome and to a lesser extent in persistently severe HELLP syndrome. Unfortunately, none of these reports gave any information about kidney lesions responsible of acute renal failure. CONCLUSION--The haemolytic uraemic syndrome is a syndrome: thrombotic microangiopathy has to be proven when treatment by PE is planned, except in some severe clinical circumstances. PMID- 7985953 TI - Long-term plasma exchange. Analysis of indications, outcome and side effects. AB - In order to determine the characteristics and the course of diseases treated with long-term plasmapheresis (e.g., more than 25 plasma exchanges), we retrospectively studied 850 patients who underwent plasmapheresis. Long-term plasma exchange was prescribed to 38 patients who failed to respond to conventional therapy; cryoglobulinemias, peripheral neuropathies and monoclonal gammopathies were their most frequent underlying diseases. Improvement was noted in 65.8% cases. Only minor side effects were observed and the risk/benefit ratio for such therapy was excellent. PMID- 7985954 TI - [Rapidly progressive glomerulonephritis treated by apheresis. A major economic challenge]. AB - Since 1983, 28 patients with a rapidly progressive glomerulonephritis were treated with apheresis. Seventeen patients had a primary glomerulonephritis, while 11 had a secondary form. Pathological pattern showed crescentic glomerulonephritis in all cases but one. In 23 cases of 28, renal survival was compromised within a few months. Apheresis were performed with the filtration technique, using a single needle device and central venous catheter. Plasmafilters were reused since 1984. In 1987, cascade filtration was introduced. The procedure was under permanent medical control. Mean reuse rate was 6 time. Renal actuarial survival curve showed a 60%, 42% and 21% survival rate at respectively 1, 2 and 5 years. Five deaths were noted. No death occurred during the apheresis procedure. The mean cost of filters and blood lines was 490 French francs (FF) per session; the mean cost of an haemodialysis session was 1900 FF. When the real survival time was compared to the expected renal failure without apheresis (assuming a linear progression of the disease), patients with a positive response to apheresis saved 488 dialysis months. The amount saved was 12 MFF. The additive cost of inefficient apheresis was 0.06 MFF. These data have to be considered on a 0.5 M inhabitants population basis during a 10 year survey. PMID- 7985955 TI - [Hemolytic-uremic syndrome disclosing lymphoma]. PMID- 7985956 TI - [Multiple autoimmune syndrome: succession of bullous pemphigoid, endocapillary proliferative glomerulonephritis, Guillain-Barre syndrome and idiopathic thrombocytopenic purpura: cascade-apheresis or "the panacea"?]. PMID- 7985957 TI - [Severe hyperviscosity syndrome in a HIV-seropositive patient. Value of plasma exchange]. PMID- 7985958 TI - The vast "waistland": a rediscovered area in liposuction. PMID- 7985959 TI - Clinical impact of breast implant magnetic resonance imaging. AB - Magnetic resonance imaging has become the state-of-art technique to diagnose the loss of silicone gel-filled mammary implant integrity (rupture, gel leak). In a series of 39 patients considering implant removal (40 procedures, 74 devices), the impact of magnetic resonance imaging on the decisions made by the patient and surgeon was examined. In this selected group of patients, implant rupture or gel leak was found in 17 patients (16 grossly ruptured devices and 7 with gel leak). In 9 (53%) of these patients, magnetic resonance imaging was the decisive factor leading to the request for explantation by the patient. Diagnosis of implant rupture based on history and physical examination was made in 4 patients (confirmed in 3 and negated by magnetic resonance imaging and intraoperatively in 1). In 10 of the 14 remaining patients (26%) with "unexpected" loss of implant integrity (negative history and physical examination), magnetic resonance imaging evidence was the decisive factor for advising explantation by the surgeon. Negative magnetic resonance imaging results did not influence the patient's or surgeon's decisions. Magnetic resonance imaging appears to be a sensitive and specific technique, and there were no false-negative and one false-positive (gel leak diagnosis) findings in this series. PMID- 7985960 TI - Comparison of mammography, sonography, and magnetic resonance imaging in the detection of silicone-gel breast implant rupture. AB - Silicone-gel breast implant rupture is difficult to diagnose preoperatively. A variety of radiological methods have been used for diagnosis. This study prospectively compares film-screen mammography, high-resolution sonography, and magnetic resonance imaging in the diagnosis of implant rupture using predetermined diagnostic criteria. Thirteen patients (24 implants) underwent film screen mammography, sonography, and magnetic resonance imaging to evaluate the integrity of their implants. All patients subsequently underwent surgical removal of the implants. Preoperatively, the integrity of each implant was rated on a three-level classification system on the basis of one modality by a reviewer who was unaware of the results of the other two modalities. The three imaging modalities achieved the following sensitivities and specificities, respectively: mammography, 69% and 82%; sonography, 54% and 64%; MRI, 69% and 55%. Even though each modality addresses some of the limitations of the others, in this group of patients, there was no clearly superior imaging tool. PMID- 7985961 TI - Magnetic resonance imaging of in situ mammary prostheses. AB - A study was conducted at the University of Virginia Health Sciences Center to examine the effectiveness of magnetic resonance imaging in detecting rupture or deflation of in situ mammary prostheses. Thirty-three women with 59 prostheses were included in the study. Fifteen of the 33 patients had undergone surgery for removal or replacement of 21 implants. Positive findings for rupture were accurately predicted for 15 implants and confirmed at surgery. Negative findings for rupture were accurately predicted in the remaining 6 implants and confirmed at surgery. Although it is a more costly procedure than either mammography or ultrasonography, we believe that magnetic resonance imaging is also more accurate in detecting damaged implants, particularly when they are contained within an intact capsule or when the implants are stacked. Unlike mammography, magnetic resonance imaging requires no ionizing radiation or breast compression. Magnetic resonance imaging of the in situ breast prosthesis may be a useful adjunct when other modalities yield inconclusive results or when a contained rupture is suspected. PMID- 7985962 TI - Treatment considerations in postmastectomy reconstruction: their relative importance and relationship to patient satisfaction. AB - Although studies concerning motivation for and satisfaction with breast reconstruction after mastectomy have proliferated, little information is available concerning the relative importance of motivating factors and satisfaction with treatment choice in nonreconstructed and reconstructed mastectomy patients. We studied this by questioning 144 women in four groups: mastectomy patients who had reconstruction; mastectomy patients who did not have reconstruction; and two control groups composed of women who had not had any cancer or who had undergone hysterectomy for uterine cancer. This study was conducted just before the reports of alleged risks of silicone to the patients and reflects the opinions of patients without such bias. This study shows that, although women who opted for reconstruction reported greater concern about appearance than women who did not have reconstruction, both groups described concerns about surgical discomfort and possible complications. Also, women's concerns about appearance did not seem to fall solely into public (others' evaluations) or private (patients' own evaluation) domains. Rather, personal attitudes about appearance may affect interpersonal experiences. Finally, concerns about the possibility of recurrence may reduce patient satisfaction for some women who have reconstruction, so postsurgical education regarding cancer risk may be needed. Reconstructed and nonreconstructed mastectomy patients do not appear to differ in postoperative behaviors promoting personal health. This information, analyzed before the silicone controversy, may serve as a baseline for future research on the impact of the silicone crisis on women's perceptions regarding reconstruction. PMID- 7985963 TI - Use of previously burned skin in local fasciocutaneous flaps for upper extremity reconstruction. AB - Thermal injuries are characterized by varying degrees of damage to the skin and underlying structures. In the vast majority of patients, the initial thermal injury is limited to the skin and subcutaneous fat. The underlying fascia and its vasculature usually are spared. Flaps are required to cover nongraftable wounds (exposed tendon, bone, joints, and so on) and also are used to release joint and web space contractures. Contrary to frequent opinion, previously burned skin or skin-grafted fascia can safely be used as fasciocutaneous flaps when necessary. We present our series of burned patients in whom local flaps originating from within the burned area were used, avoiding the need for more distant or free flaps to accomplish appropriate wound coverage. This series consists of 40 fasciocutaneous flaps in 22 patients. The flaps included lateral arm (4), posterior interosseous (7), radial forearm (4), ulnar forearm (2), metacarpal (3), and digital (20). PMID- 7985964 TI - Reverse dorsometacarpal flap in digits and web-space reconstruction. AB - Skin defects in some areas of the digits are difficult to reconstruct, such as the ulnar aspect of the little or ring finger, radial aspect of the index, dorsal or volar aspect of fingers with proximal interphalangeal or metacarpophalangeal joint involvement, and proximal phalanx of the thumb. Moderate or severe contracture of the web space and multiple finger injuries without an available cross-finger flap are also a challenge to reconstructive surgeons. The reverse dorsometacarpal flap presents an option for reconstruction because of these difficulties. It is reliable and versatile in design. The donor site can be closed primarily provided the flap is less than 2 cm wide. PMID- 7985965 TI - Successful transplantation of cultured human outer root sheath cells as epithelium. AB - We used sheets of cultured outer root sheath cells derived from plucked human hair follicles for the epidermal reconstruction of a burn wound of a patient and prepared wounds of athymic mice. The outer root sheath cells obtained from plucked human follicles can grow in serial culture in a defined medium without serum. After seven subcultures within 5 weeks, outer root sheath cells obtained from a single follicle grew approximately 1 x 10(7) cells, which covered a 360 cm2 area of a monolayer sheet. These cultured outer root sheath cells, carried on a bovine atelocollagen sheet (Meipac) or a polyurethane sheet (Tegaderm), were transplanted on a graft bed prepared on the backs of athymic mice. Contraction of the graft beds was prevented by the use of these carriers. Histological examination of the graft removed 2 weeks after transplantation showed four to seven layers of epithelial cells. Both the epidermal granular and horny cell layers were well developed, although the rete ridges were absent. Using the same technique, the sheet of outer root sheath cells with an atelocollagen as a carrier was successfully transplanted onto the granulating site in a burn patient. PMID- 7985966 TI - Light microscopic and immunohistochemical features in serial biopsies of epidermal versus dermal allografts. AB - The local immune response to allograft dermis and epidermis was studied in a rat skin-graft model. Biopsies taken at varying times after transplantation were analyzed using routine light microscopy and a panel of monoclonal antibodies. The dermis appeared to be spared by the rejection process, whereas the epithelium and adnexal elements of the dermis were destroyed. The persistence of dermis transplanted across major histoincompatibilities may allow it to be useful in reconstructing large skin losses. PMID- 7985967 TI - Subungual glomus tumors: an algorithmic approach. AB - Glomus tumors of the hand are benign lesions that historically have often eluded a timely diagnosis and effective therapy. The reason for this difficulty in diagnosis lies partially in the rarity of these lesions. A certain degree of suspicion as well as a knowledge of the appropriate workup are necessary. In this article we submit an algorithmic approach to the diagnosis and treatment of these lesions as a guideline for clinical management. A description of our preferred method of extirpation is provided. PMID- 7985968 TI - Vertical preputial flap with double skin island for correction of hypospadias with severe recurvatum. AB - Eight patients presenting with a proximal hypospadias and penis recurvatum have been operated on. A one-stage procedure, based on the vertical preputial island flap operation, was the option for surgery. To reconstruct the missing urethra and the ventral skin defect, after the correction of the curvature, a single flap carrying two skin islands, useful for both goals, was planned. The urethroplasty was performed using the dorsal aspect of the island flap, according to Scuderi's operation, and the skin defect was reconstructed by means of the ventral aspect. No postoperative complication occurred. In all patients it was possible to place the meatus at the apex of the glans and to reconstruct the ventral skin continuity. The use of the vertical, "double-face," preputial island flap technique is suggested for single-stage repair of proximal hypospadias with severe recurvatum, presenting long urethral and large ventral skin defects. PMID- 7985969 TI - Clostridial infection following severe facial trauma. AB - Severe posttraumatic wound infections are uncommon occurrences in the craniofacial region. Although most reported cases have occurred following an odontogenic infection or minor soft-tissue trauma, the potential for the development of this type of infection exists following complex facial fractures. We report a case with clostridial infection in the temporalis fascia complicating a complex facial fracture. The implications regarding antibiotic usage and delay of surgical treatment are discussed. PMID- 7985971 TI - Congenital epulis: evidence against the intrauterine estrogen stimulus theory. AB - A rare case of congenital epulis is presented. The tumor growth, as a result of intrauterine hormonal stimuli, is discussed along with evidence against the intrauterine estrogen stimulus theory. PMID- 7985970 TI - The combined latissimus dorsi and scapular free flap for the complex anterior neck defect after enlarged total laryngectomy. AB - Combined latissimus dorsi musculocutaneous and scapular fasciocutaneous free flap were successfully used to reconstruct two complex pharyngolaryngectomy defects with no anterior neck skin. The cervical esophagus and hypopharynx were reconstructed with the scapular portion, and the latissimus segment restored the anterior neck skin. One defect was reconstructed immediately, and the other followed an earlier ablation. PMID- 7985972 TI - Pilonidal sinus of the axilla: report of five patients and review of the literature. AB - Five patients with a pilonidal sinus of the axilla--thought to be the 9th to 13th described in the literature--are reported. All patients were nonhirsute, healthy women aged 17 to 30 years. One or two hairs were seen macroscopically and histologically in 3 of 5 patients, and 1 hair was seen macroscopically in the remaining 2 patients. Friction (abduction-adduction) or suction, as well as assorted factors such as shaving, minor infection, and maceration, seemed to be the most probable cause of pilonidal sinus of the axilla. Complete resection, including the openings of 1 or 2 sinuses, is the only suitable treatment for axillary suppuration. PMID- 7985973 TI - "Congenital" common peroneal nerve compression. AB - Common peroneal nerve palsies may arise from numerous causes. We report an unusual case of common peroneal nerve palsy secondary to a previously unreported congenital band crossing the nerve at the level of the fibular head. PMID- 7985975 TI - Thomas Dent Mutter, MD: early reparative surgeon. AB - Thomas Dent Mutter (1811-1859) was one of the early American pioneers of plastic surgery. He studied under some of the great teachers in Europe during the early 19th century and returned to the United States as a professor of surgery at Thomas Jefferson University in Philadelphia. He was renowned for his operations on clubfoot, cleft lip and palate, congenital anomalies, and mutilating injuries. He is best known for the cervical flap that bears his name. His contributions include an endowment for a medical museum that bears his name to which he donated a large collection of his medical specimens. The Mutter Museum prospers to this day. His ideas and innovations have influenced many students of plastic surgery both during his lifetime and today. PMID- 7985974 TI - Blastomycosis infection of the hand. AB - Blastomycosis is an uncommon cause of infection in the hand. Fungal infection should be suspected in any case when expected improvement does not occur with appropriate antibiotic therapy and wound care. We describe a rare case of primary blastomycosis of the hand that progressed to severe soft tissue destruction and significant loss of hand function. PMID- 7985976 TI - Role of human papillomavirus in cutaneous oncogenesis. AB - There is a strong association between the human papillomavirus and cutaneous squamous cell carcinoma. If this association was merely random, one would expect an equal distribution of human papillomavirus types among affected individuals. However, only specific types of human papillomavirus are consistently found in cutaneous and genital squamous cell carcinomas. Immunosuppressed individuals clearly have a much higher incidence of cutaneous carcinomas. Immunosuppression, either local or systemic, not only decreases immune surveillance but may also dictate the amount and type of virus each individual may carry. Epidermodysplasia verruciformis and other rare hereditary disorders that combine specific immune defects and an increased incidence of malignancy are very useful models that clearly fulfill a multistep theory of oncogenesis. The precise mechanism of oncogenesis in these select human papillomavirus types is not yet fully understood. Intracellular interactions with the recently described tumor suppressor proteins may prove to be the primary site of action of these oncogenic viruses. Environmental cocarcinogens and activation of oncogenes are clearly important if not essential factors in human papillomavirus-associated tumors. As our knowledge and understanding of malignant transformation grows, it becomes apparent that this is a complex multistep process. PMID- 7985977 TI - First we are physicians. PMID- 7985978 TI - [Genetic instability in Portulaca grandiflora (Hook)]. AB - Portulaca grandiflora, a member of the Centrospermae, produces the alkaloid-type betalain pigment in its petals and stems. Variegation patterns were observed on the corolla of some clones. The authors postulate that in Portulaca grandiflora a relation exist between unstable mutations and the presence of transposable elements in the genome. Experiments with unstable mutants of Portulaca grandiflora having variegated flowers were done. The unstable loci cmI and rmI, which are involved in betalain synthesis were genetically analysed. PMID- 7985979 TI - Molecular cytogenetic analysis of a series of 23 DiGeorge syndrome patients by fluorescence in situ hybridization. AB - The authors have studied a series of 23 DiGeorge syndrome patients by prometaphase chromosome analysis and/or by FISH with a set of 6 cosmid probes spanning the previously described commonly deleted region. Four patients display a cytogenetically visible interstitial deletion in band 22q11.2, whereas the other 18 patients exhibit a molecular deletion evidenced only by FISH analysis. For 21 of the patients studied, the deletion encompasses the 6 loci tested, while for one, only the most telomeric of these loci is conserved. The last patient does not show any deletion with the probes used. PMID- 7985980 TI - [Rapid in situ detection of chromosome 21 by the PRINS technique]. AB - The PRINS technique has been used to rapidly detect chromosomes 21 in both metaphases and interphase nuclei. A specific labeling was obtained in preparations from lymphocytes and amniotic fluid cells. The method is based on annealing of specific oligonucleotide primers and subsequent primer extension by a Taq DNA polymerase. PRINS is an interesting alternative to in situ hybridization for cytogenetic diagnosis and physical mapping. PMID- 7985981 TI - [Familial thymoma and translocation t (14;20) (q24;p13)]. AB - A familial lympho-epithelial thymoma with constitutional chromosomal translocation t (14;20) (q24;p13) is presented: the thymoma and its particular translocation are present in the mother and the two sons of her offspring. The small number of cases do not allow establishing any relation between thymoma and this particular translocation. Concerning genetic counseling, an annual thoracic radiography is necessary for all the other family members, carriers or not of the translocation. PMID- 7985982 TI - Optic atrophy, microcephaly, mental retardation and mosaic variegated aneuploidy: a human mitotic mutation. AB - A 12-year-old girl presents with optic atrophy, pale papilla, amblyopia and microcephaly (-3 s.d.) with mild mental retardation and facial dysmorphism. She had mitral insufficiency with mitral prolapse and moderate short stature (-2.5 d.s.). She had normal flash visual evoked potentials, normal electroretinograms and electrooculograms and normal cranial CT scan as well as other lab tests to rule out malformations, tumors or multiple sclerosis. Her lymphocyte karyotype showed a variegated mosaicism with: 2 cells with 49, XX, +mar,+mar,+mar; 21 cells with 48, XX, +mar,+mar; 57 cells, with 47, XX,+mar; 20 cells with 46,XX; while parental karyotypes were normal. This syndrome therefore associates optic atrophy, mental retardation and microcephaly and short stature with chromosomal instability in the form of variegated mosaicism. PMID- 7985983 TI - Isochromosome-formation in chromosome 9. AB - A new case of de novo isochromosome-formation in chromosome 9 associated with the translocation of long arm material of chromosome 9 onto chromosome 1 is described. The female patient is mentally retarded and shows only minor dysmorphisms. The cytogenetic investigation revealed a two-cell-line mosaicism with different isochromosomes of chromosome 9. In both cell lines, a translocation of 9qter-9q13 onto the short arm of chromosome 1 is observed. PMID- 7985984 TI - Consanguinity and kinship in Down syndrome in Saguenay Lac-Saint-Jean (Quebec). AB - Genealogies of 67 cases of Down syndrome (DS) cytogenetically proven as trisomy 21 born in Saguenay-Lac-Saint-Jean were reconstructed using a population register. Genealogies of three controls for each patient matched on sex, date and place of birth were also reconstructed. The mean kinship coefficient was slightly, but not significantly (p > 0.05), increased in the DS group compared to the control group (0.000222 versus 0.000165). The increase was mostly the result of two patients being related as uncle-nephew. The mean inbreeding coefficient was also higher, although not significantly (p > 0.05), in the DS group than in the control group (0.001348 versus 0.000848). Nine consanguineous marriages (13.4%) were identified in the DS group compared to 17 of 201 (8.5%) in the control group. These results may suggest, as previously reported by Roberts et al. in Shetland, that some recessive element is involved in the etiology of DS, possibly in preventing the loss of the trisomic 21 fetus. PMID- 7985985 TI - Disease knowledge and reproductive attitudes of parents having a child with cystic fibrosis. AB - Saguenay Lac-Saint-Jean (SLSJ), a geographically isolated region located in northeastern Quebec, has an incidence of cystic fibrosis (CF) of 1 in 902 live births and a carrier rate of 1 in 15 inhabitants. Forty two families among those registered at the local chapters of the Canadian CF Foundation were randomly selected. A multiple-choice questionnaire was applied during an interview. It included 102 questions pertaining to the sociodemographic status of the participants, their knowledge of the disease and their reproductive attitudes. All the educational and socioeconomic levels were represented in the sample; 76% of the respondents were married. Before answering the questionnaire, 86% estimated their knowledge of the transmission of CF to be good or excellent; in fact, the rate of good answers to various questions ranged from 71 to 95%. The birth of a child with CF had a major impact on further pregnancy planning (a 69% reduction or arrest). Seventy one percent of the respondents used a more effective contraception method (including vasectomy and tubal ligation) after the birth of the CF child; in 63% of them, the decision was a direct consequence of the presence of the disease in the family. Thirty four respondents (81%) knew that prenatal diagnosis was available; 90% were in favor of such a prenatal test but only 17% would have required an abortion should the fetus be affected. PMID- 7985986 TI - A comment on the Who's Who on Mount Olympus. PMID- 7985987 TI - Chromosomal mosaicism limited to fibroblasts and MCA/MR syndrome with fetal hypokinesia of central nervous origin. PMID- 7985988 TI - Comparative length and weight growth in Khartoum infants. AB - First-year postnatal growth of supine length and body weight of a group of Khartoum infants is analysed in terms of the correlation coefficients between birth dimension on the one hand and (1) subsequent distance growth at monthly intervals and (2) the 11-monthly increments on the other. It is shown that the whole of the first-year length growth is dominated by catch-up/catch-down processes which must equally affect the infants. Weight growth is similarly affected, but to a lesser degree and for a shorter time. After 6 months of age some of the influences that determined prenatal weight growth reappear. Using data extracted from fitting growth curves to each individual the correlational analysis suggests a growth pulse in both length and weight, which is responsible for distance catch-up. PMID- 7985989 TI - Menarche in intensively trained gymnasts, swimmers and tennis players. AB - It has been hypothesized that young athletes, undertaking intensive training, have delayed menarche due to the effects of training at an early age, although it is known that other genetic and environmental factors contribute to this observed later menarche. As part of a longitudinal study of the effects of intensive training during puberty and adolescence we investigated age of menarche in 222 athletes and their mothers. All the sports studied (gymnastics, swimming and tennis) had later mean ages of menarche (14.3, 13.3 and 13.2 years respectively) than the previously reported UK reference value of 13.00 years. A positive correlation was found between menarcheal age in mothers and daughters (r = 0.27, p < 0.01). Analysis of covariance, using maternal menarcheal age, socioeconomic group, duration of training and type of sport, confirmed that maternal menarcheal age and type of sport were having a significant influence on subject's age of menarche. As maternal menarcheal age and sport were the best predictors of menarcheal age in the athletes we studied, it would appear that menarche was intrinsically late rather than delayed. This suggests that some form of sport specific selection may have occurred. It therefore seems likely that late maturation of gymnasts contributes to a girl's decision to continue participating in the sport rather than intensive training delaying menarche. PMID- 7985990 TI - Age at menarche in athletes and their mothers and sisters. AB - Retrospective ages at menarche were obtained from 109 university athletes and their mothers, and from 77 sisters of the athletes. The athletes were participants in seven sports. Mean age (+/- SD) at menarche of the 109 athletes was identical with that of the total sample of 338 athletes from which they were drawn, 13.8 +/- 1.5 years. Mean age at menarche in the mothers was 13.4 +/- 1.7 years. When mothers were grouped as having been athletes (n = 52) or non-athletes (n = 57), menarcheal ages were, respectively, 13.7 +/- 1.8 years and 13.2 +/- 1.5 years. The mother-daughter correlation for age at menarche was 0.25. Corresponding correlations between athletes and mothers who were athletes and between athletes and mothers who were not athletes were 0.24 and 0.22, respectively. Ages at menarche in athletes who had sisters (n = 62) and their sisters (n = 77) were 14.0 +/- 1.4 and 13.6 +/- 1.6 years, respectively. The intraclass sister-sister correlation was 0.44. Familial resemblance in age at menarche in athletes, their mothers and sisters, is identical with that in the general population, and suggests that later menarche commonly observed in athletes is to a large extent familial. PMID- 7985992 TI - Adolescent height growth of US children. PMID- 7985991 TI - MZ twinning: chance or determinism? An essay in nonlinear dynamics (chaos). AB - Classically, researchers considered monozygotic twinning (MZT) a random phenomenon. This paper tests the hypothesis with the aid of nonlinear dynamics techniques. The latter can tell true randomness from chance-like variation. Chaos, the endpoint of the threshold state of a nonlinear deterministic system, can mimic constrained randomness. From a practical standpoint, recognizing chaos in a time series data set means that the paradigmatic multifactorial model of causation is essentially ruled out. Specifically, time series of MZ, DZ, and single maternities were analysed. First, spectral analysis was used to uncover periodicities embedded in the series. Second, a singular value decomposition was undertaken to reduce noise from the series. Third, phase space attractors were drawn up that describe the 'asymptotic' trajectory of the system at any time. Results suggested that DZ, MZ, and single maternities shared a similar 32-year periodicity. Owing to two interwoven similar periodicities, the single-maternity cycle kinetics proved to be faster than that of DZ's. The MZ series was the only one to display secondary interacting harmonics, thus eliciting a rather unusual trajectory in the bidimensional phase space. The MZ time points were not spread in a haphazard fashion; on the contrary, a fine structure was present that did not reduce to a limit cycle such as the one characterizing the DZ- or the single maternity trajectory. It was concluded that a complex nonlinear dynamic underlies MZ twinning. Therefore, calling for extrinsic causes to account for what appears to be random variation overtime would be pointless. MZ twinning should rather be traced to a limited number of intrinsic and deterministic interacting system components. The most likely candidates are presented and discussed. PMID- 7985993 TI - Distribution of plasma alpha-1-B-glycoprotein (A1BG) polymorphism in several populations of the Indian subcontinent. AB - The distribution of plasma alpha 1B-glycoprotein (A1BG) was determined by a two dimensional electrophoresis (agarose-polyacrylamide gel) followed by protein staining in a group of 1099 individuals from 11 populations of the Indian subcontinent. The sample comprised 454 from several tribes of Arunachal Pradesh; 76 Bengali Hundus and 88 Bengali Muslims; 179 Tamil Hindus from Singapore and 107 from India; 81 Tamil Muslims, 48 Sinhalese from Sri Lanka and 66 North Indians. Three common A1BG phenotypes (1-1, 1-2 and 2-2) were observed in this study. One each of a new allele (A1BG*7) in heterozygous form (1-7) was detected respectively among Tamil Hindus of India and Singapore. The phenotypic distribution of A1BG alleles was at Hardy-Weinberg equilibrium in all the populations. The frequency of A1BG*2 was in general lower in the Mongoloid tribes of Arunachal Pradesh (0.043-0.104) and North Indians (0.068) compared to that in other Indian populations (0.130-0.171) and Sinhalese (0.208). PMID- 7985994 TI - Growth in length and weight from birth to 2 years of a representative sample of Netherlands children (born in 1988-89) related to socioeconomic status and other background characteristics. AB - Of nearly 1900 live-born singletons, born from April 1988 to October 1989 inclusive, nine measurements of length and weight have been taken between the ages of 1 and 24 months. In the first part of the study, differences in attained length and weight at 1 and 2 years of age are analysed according to socioeconomic status (SES). Multiple regression analyses are used to investigate the association of SES and other background characteristics with length and weight. The second part focuses on the analysis of differences in linear length and weight gain in the first 2 years of life, using a two-step regression technique. At 1 and 2 years of age, differences in attained length and weight and in length and weight gain according to SES are small and not significant, except for the children of Mediterranean parents in the low-SES group, who are significantly heavier than children of all other groups and gain significantly more in weight compared to children of Dutch parents in the low-SES group. Of all the factors studied it appears that parental height, birthweight, parity and ethnic descent of the parents are associated with attained length and weight at 1 and 2 years of age. Of these factors, ethnic descent, however, is not associated with length gain. A small but statistically significant catch-up growth is found in children of mothers who smoked during pregnancy. PMID- 7985995 TI - Further blood genetic studies on Amazonian diversity--data from four Indian groups. AB - Information related to 31 protein genetic systems was obtained for 307 individuals affiliated with the Cinta Larga, Karitiana, Surui and Kararao Indians of northern Brazil. In terms of genetic distances the Cinta Larga showed more similarities with the Karitiana (both are Tupi-speaking tribes), while at a more distant level the Surui clustered with the Kararao. The latter, a Cayapo subgroup, showed a completely different genetic constitution from the other subgroups of this same tribe. Both the Kararao and Karitiana are small, remnant populations, and their gene pools have presumably been severely affected by random and founder effects. These results were incorporated with those of 25 other Amazonian Indian tribes, and analysis by two multivariate techniques confirmed a previously observed geographical dichotomy, suggesting either that the Amazon river constitutes a barrier to north-south gene flow or that latitudinally different past migrations entered the region from the west. PMID- 7985996 TI - A physiological adaptation to undernutrition. AB - A total of 432 children under the age of 10 years were measured for height and weight, and the morbidity and mortality indices were studied in six counties of the maize region of the state of Yucatan, Mexico. Undernutrition, because of its relationship to morbidity and mortality, was considered an important selection factor operating between the ages of 6 and 24 months. It was also observed that short stature was an adaptive response to the first years of undernutrition, that allowed children to maintain an adequate body weight under conditions of nutritional stress during the first 10 years of life. PMID- 7985997 TI - Serum therapy revisited: animal models of infection and development of passive antibody therapy. PMID- 7985998 TI - Teicoplanin alone or combined with rifampin compared with vancomycin for prophylaxis and treatment of experimental foreign body infection by methicillin resistant Staphylococcus aureus. AB - The prophylactic and therapeutic activities of teicoplanin were evaluated in two different experimental models of foreign body infections caused by methicillin resistant Staphylococcus aureus (MRSA). In a guinea pig model of prophylaxis, subcutaneously implanted tissue cages were infected at a > 90% rate by 10(2) CFU of MRSA in control animals. A single dose of 30 mg of teicoplanin per kg of body weight administered intraperitoneally 6 h before bacterial challenge was as effective as vancomycin in preventing experimental infection in tissue cages injected with either 10(2), 10(3), or 10(4) CFU of MRSA. In a rat model evaluating the therapy of chronic tissue cage infection caused by MRSA, the efficacy of a 7-day high-dose (30 mg/kg once daily) regimen of teicoplanin was compared with that of vancomycin (50 mg/kg twice daily). Whereas high levels of teicoplanin were found in tissue cage fluid, continuously exceeding its MBC for MRSA by 8- to 16-fold, no significant reduction in the viable counts of MRSA occurred during therapy. In contrast, either vancomycin alone or a combined regimen of high-dose teicoplanin plus rifampin (25 mg/kg twice daily) could significantly decrease the viable counts in tissue cage fluids. Whereas the bacteria recovered from tissue cage fluids during therapy showed no evidence of teicoplanin resistance, they failed to be killed even by high levels of this antimicrobial agent. The altered susceptibility of in vivo growing bacteria to teicoplanin killing might in part explain the defective activity of this antimicrobial agent when used as monotherapy against chronic S. aureus infections. These data may indicate the need for a combined regimen of teicoplanin with other agents such as rifampin to optimize the therapy of severe staphylococcal infections. PMID- 7985999 TI - Molecular and genetic analysis of the Bacteroides uniformis cephalosporinase gene, cblA, encoding the species-specific beta-lactamase. AB - The gene, cblA, encoding the species-specific, clavulanate-susceptible, endogenous cephalosporinase was cloned from Bacteroides uniformis WAL-7088. The nucleotide sequence was determined, and the cblA structural gene was found to be 891 nucleotides, with a 48% G+C composition, which is similar to that of the B. uniformis genome. The cblA open reading frame encoded an Ambler class A beta lactamase polypeptide precursor of 296 amino acid residues with a predicted molecular weight of 33,450. A beta-lactamase-deficient B. uniformis mutant with increased beta-lactam susceptibility was constructed by insertional inactivation of the chromosomal gene. This mutant was complemented by plasmids bearing the cblA gene, and the resulting strains were resistant to cephaloridine and had a beta-lactamase that comigrated with the parental beta-lactamase on sodium dodecyl sulfate-polyacrylamide gel electrophoresis (30,500 Da) and in isoelectric focusing gels (pI 4.6), confirming a role for this beta-lactamase in resistance. PMID- 7986001 TI - Intermittent azithromycin for treatment of Mycobacterium avium infection in beige mice. AB - The activity of azithromycin (AZI) was evaluated in the beige mouse model of disseminated Mycobacterium avium infection. Mice were infected intravenously with approximately 10(7) viable avium ATCC 49601. AZI at 50, 100, or 200 mg/kg of body weight or clarithromycin (CLA) at 200 mg/kg was given by gavage 5 days per week for 4 weeks. Groups of treated mice were compared with untreated control animals. A dose-related reduction in cell counts in organs was observed with AZI treatment. AZI at 200 mg/kg was more active than CLA at 200 mg/kg against organisms in spleens. The activities of these two agents at 200 mg/kg were comparable against organisms in lungs. In a second study, AZI at 200 mg/kg was given daily for 5 days; this was followed by intermittent AZI treatment for the next 3 weeks. The activities of AZI given on a three-times- and five-times-per week basis in the continuation phase were comparable. AZI given on a once-weekly basis was less active. The regimen of AZI given in combination with rifapentine on a once-weekly basis for 8 weeks showed promising activity. Clinical evaluation of AZI and rifapentine will help to define the roles of these agents in the treatment of disseminated M. avium complex infection. PMID- 7986000 TI - Comparison of ofloxacin and ceftriaxone for short-course treatment of enteric fever. AB - An open, randomized comparison of ofloxacin (200 mg, every 12 h) given orally for 5 days and ceftriaxone (3 g, once daily) given intravenously for 3 days in the treatment of uncomplicated enteric fever was conducted in Ho Chi Minh City, Vietnam. Salmonella paratyphi type A was isolated from six patients. Salmonella typhi was isolated from 41 patients; 63% of these isolates were resistant to multiple antibiotics: ampicillin, chloramphenicol, sulfamethoxazole, trimethoprim, and tetracycline. Of the culture-confirmed cases, treatment with ofloxacin resulted in complete cure of all 22 patients, whereas 18 of 25 patients treated with ceftriaxone were completely cured (P < 0.01). In the ceftriaxone group, there were six acute treatment failures and one relapse. Mean +/- standard deviation fever clearance times were 81 +/- 25 h for ofloxacin and 196 +/- 87 h for ceftriaxone (P < 0.0001). Short-course treatment with oral ofloxacin (5 days) is significantly better than that with ceftriaxone (3 days) and will be of particular benefit in areas where multiresistant strains of S. typhi are encountered. PMID- 7986002 TI - Quantitative relationships between zidovudine exposure and efficacy and toxicity. AB - We examined the relationship between the concentrations of zidovudine in plasma given by continuous intravenous infusion to human immunodeficiency virus-positive pediatric patients and a surrogate marker of outcome (measured by the increase in the number of CD4-positive T cells) as well as drug-mediated toxicity (change in granulocyte count). The return of CD4-positive T cells was most strongly related to the number of these cells present at the start of therapy. Drug concentration data added little explanatory power to this relationship, indicating that the effect of zidovudine was near maximal throughout the range of concentrations examined. The change in granulocyte count was significantly correlated with zidovudine concentration both from weeks 1 through 8 and from weeks 8 through 12. These findings imply that it may be wise to stratify phase I antiretrovirus drug trials for the entry level of CD4-positive T cells if pharmacodynamic relationships with this marker as the dependent variable are to be sought. Continued efforts need to be made to derive quantitative relationships between drug exposure and measures of both efficacy and toxicity so that the maximal amount of information is derived from small phase I studies. PMID- 7986003 TI - Role of efflux pump(s) in intrinsic resistance of Pseudomonas aeruginosa: resistance to tetracycline, chloramphenicol, and norfloxacin. AB - Most strains of Pseudomonas aeruginosa are significantly more resistant, even in the absence of R plasmids, to many antimicrobial agents, including beta-lactams, tetracycline, chloramphenicol, and fluoroquinolones, than most other gram negative rods. This broad-range resistance has so far been assumed to be mainly due to the low permeability of the P. aeruginosa outer membrane. The intrinsic resistance phenotype becomes further enhanced in "intrinsically carbenicillin resistant" isolates, which were often assumed to produce outer membranes of even lower permeability. It has been shown, however, that this hypothesis cannot explain the beta-lactam resistance of these isolates (D.M. Livermore and K.W.M. Davy, Antimicrob. Agents Chemother. 35:916-921, 1991). In this study, we examined the uptake of tetracycline, chloramphenicol, and norfloxacin by intact cells using strains showing widely different levels of intrinsic resistance. Their accumulation and the response to the addition of a proton conductor showed that even relatively susceptible strains of P. aeruginosa actively pump out these compounds from the cell and that the efflux activity becomes much stronger in strains showing higher levels of intrinsic resistance. We conclude that the efflux mechanism(s) are likely to contribute significantly to the intrinsic resistance of P. aeruginosa isolates to tetracycline, chloramphenicol, and fluoroquinolones, as does the low permeability of the outer membrane. This conclusion is supported by the observation that the hypersusceptibility to various agents of the mutant K799/61 (W. Zimmermann, Antimicrob. Agents Chemother. 18:94-100, 1980) was apparently caused by the lack of active efflux. Although the hypersusceptibility of this mutant has hitherto been assumed to be solely due to its higher outer membrane permeability, its outer membrane was shown to have a coefficient of permeability to cephaloridine that was not significantly different from that of the parent, resistant strain K799/WT. The strains with elevated intrinsic resistance overproduced two cytoplasmic membrane proteins and one outer membrane protein; at least two of these proteins appeared different from the proteins overproduced in the recently described mutant with a derepressed multidrug efflux system, MexA-MexB-OprK (K. Poole, K. Krebes, C. McNally, and S. Neshat, J. Bacteriol. 175:7363-7372, 1993). PMID- 7986004 TI - Role of efflux pump(s) in intrinsic resistance of Pseudomonas aeruginosa: active efflux as a contributing factor to beta-lactam resistance. AB - Wild-type strains of Pseudomonas aeruginosa are more resistant to various beta lactam antibiotics as well as other agents than most enteric bacteria. Although resistance to compounds of earlier generations is explained by the synergism between the outer membrane barrier and the inducible beta-lactamase, it was puzzling to see significant levels of resistance to compounds that do not act as inducers or are not hydrolyzed rapidly by the chromosomally encoded enzyme. This intrinsic-resistance phenotype becomes enhanced in those strains with the so called intrinsic carbenicillin resistance. In the accompanying paper (X.-Z. Li, D. M. Livermore, and H. Nikaido, Antimicrob. Agents Chemother. 38:1732-1741, 1994), we showed that active efflux played a role in the resistance, to various non-beta-lactam agents, of P. aeruginosa strains in general and that the efflux was enhanced in intrinsically carbenicillin-resistant strains. We show in this paper that, in comparison with the drug-hypersusceptible mutant K799/61, less benzylpenicillin was accumulated in wild-type strains of P. aeruginosa and that the accumulation levels were even lower in intrinsically carbenicillin-resistant strains. Deenergization by the addition of a proton conductor increased the accumulation level to that expected for equilibration across the cytoplasmic membrane. In intrinsically carbenicillin-resistant isolates, there was no evidence that either nonspecific or specific permeation rates of beta-lactams across the outer membrane were lowered in comparison with those of the more susceptible isolates. Furthermore, these carbenicillin-resistant isolates were previously shown to have no alteration in the level or the inducibility of beta lactamase and in the affinity of penicillin-binding proteins. These data together suggest the involvement of an active efflux mechanism also in the resistance to beta-lactams. Hydrophilic beta-lactams with more than one charged group did not cross the cytoplasmic membrane readily. Yet one such compound, ceftriaxone, appeared to be extruded from the cells of more-resistant strains, although with this compound effects of proton conductors could not be shown. We postulate that wild-type strains of P. aeruginosa pump out such hydrophilic beta-lactams either from the periplasm or from the outer leaflet of the lipid bilayer of the cytoplasmic membrane, in a manner analogous to that hypothesized for multidrug resistance protein of human cancer cells (M.M. Gottesman and I. Pastan, Annu. Rev. Biochem. 62:385-427, 1993). PMID- 7986005 TI - Antimalarial activity of WR 243251, a Dihydroacridinedione. AB - WR 243251 is a dihydroacridinedione that was evaluated for antimalarial blood schizonticidal activity in vitro and in vivo. The in vitro doses calculated to kill 50% of organisms were 11 nM for a chloroquine-susceptible, mefloquine resistant standard strain and 25 nM for a chloroquine- and pyrimethamine resistant standard strain. The total dose needed to cure 100% of mice infected with a drug-susceptible strain of Plasmodium berghei was 12 to 20 mg/kg of body weight for both oral and subcutaneous administration. The regimen needed to cure 100% of Aotus monkeys infected with Plasmodium falciparum was 8 mg/kg/day for 3 days (chloroquine-susceptible strain) and 16 mg/kg/day for 3 days (chloroquine resistant strain). The 100% curative doses for Aotus monkeys did not increase for parasites previously exposed to subcurative doses. The absolute value of the curative doses of WR 243251 was comparable to or lower than the values for clinical antimalarial agents. The high absolute activity, comparability of activities against susceptible and resistant parasites, and inability to induce resistance by exposure to subcurative doses suggest that WR 243251 has strong potential as a blood schizonticidal agent. PMID- 7986006 TI - Protective effects of sparfloxacin in experimental pneumonia caused by Chlamydia pneumoniae in leukopenic mice. AB - The in vivo antichlamydial activities of sparfloxacin and reference drugs were examined in a experimental model of pneumonia caused by Chlamydia pneumoniae in leukopenic mice; their in vitro activities were also examined. The most potent agents in vitro were sparfloxacin (MICs for C. pneumoniae Kajaani and IOL 207, (0.031 and 0.031 micrograms/ml, respectively), clarithromycin (0.031 and 0.031 micrograms/ml, respectively), and minocycline (0.031 and 0.031 micrograms/ml, respectively); these were followed by tosufloxacin (0.063 and 0.125 micrograms/ml, respectively) and ofloxacin (0.5 and 0.5 micrograms/ml, respectively). The MBCs of sparfloxacin, tosufloxacin, ofloxacin, clarithromycin, and minocycline for these two strains were 0.063 and 0.063 micrograms/ml, 0.125 and 0.25 micrograms/ml, 1.0 and 1.0 micrograms/ml, 0.125 and 0.125 micrograms/ml, and 0.25 and 0.25 micrograms/ml, respectively. Fatal pneumonia was induced by intranasal inoculation of cyclophosphamide-treated leukopenic mice with C. pneumoniae IOL 207; infiltration of neutrophils and lymphocytes was observed in the lungs of these mice by histopathological examination. The 50% effective dose of sparfloxacin (oral dose of 0.97 mg/kg of body weight) against the pneumonia was the lowest among the drugs tested; this was followed by those of minocycline (2.22 mg/kg), tosufloxacin (3.47 mg/kg), clarithromycin (4.66 mg/kg), and ofloxacin (16.6 mg/kg). The results indicate that it may be worthwhile to use sparfloxacin against C. pneumoniae infections in humans. PMID- 7986007 TI - Genetic relationship between soxRS and mar loci in promoting multiple antibiotic resistance in Escherichia coli. AB - Multiple antibiotic resistance in Escherichia coli has typically been associated with mutations at the mar locus, located at 34 min on the E. coli chromosome. A new mutant, marC, isolated on the basis of a Mar phenotype but which maps to the soxRS (encoding the regulators of the superoxide stress response) locus located at 92 min, is described here. This mutant shares several features with a known constitutive allele of the soxRS gene, prompting the conclusion that it is a highly active allele of this gene. The marC mutation has thus been given the designation soxR201. This new mutant was used to examine the relationship between the mar and sox loci in promoting antibiotic resistance. The results of these studies indicate that full antibiotic resistance resulting from the soxR201 mutation is partially dependent on an intact mar locus and is associated with an increase in the steady-state level of mar-specific mRNA. In addition, paraquat treatment of wild-type cells is shown to increase the level of antibiotic resistance in a dose-dependent manner that requires an intact soxRS locus. Conversely, overexpression of MarA from a multicopy plasmid results in weak activation of a superoxide stress response target gene. These findings are consistent with a model in which the regulatory factors encoded by the marA and soxS genes control the expression of overlapping sets of target genes, with MarA preferentially acting on targets involved with antibiotic resistance and SoxS directed primarily towards components of the superoxide stress response. Furthermore, compounds frequently used to induce the superoxide stress response, including paraquat, menadione, and phenazine methosulfate, differ with respect to the amount of protection provided against them by the antibiotic resistance response. PMID- 7986008 TI - Inhibition of alpha-glucosidase I of the glycoprotein-processing enzymes by 6-O butanoyl castanospermine (MDL 28,574) and its consequences in human immunodeficiency virus-infected T cells. AB - The 6-O-butanoyl derivative of castanospermine (MDL 28,574) was previously shown to be approximately 30-fold more potent than the naturally occurring molecule at inhibiting the replication of human immunodeficiency virus (HIV) (D. L. Taylor, P. S. Sunkara, P. S. Liu, M. S. Kang, T. L. Bowlin, and A. S. Tyms, AIDS 5:693 698, 1991). We now report that consistent with its improved anti-HIV activity, MDL 28,574 is more effective (50% inhibitory concentration [IC50], 20 microM) than the parent molecule (IC50, 254 microM) at causing the accumulation of glucosylated oligosaccharides in HIV-infected cells by inhibition of glycoprotein processing. These were predominantly of the glucose 3 type, as determined by P4 Bio-Gel analysis after digestion with purified alpha-glucosidase I, indicating that, intracellularly, this enzyme is the major target for inhibition. MDL 28,574, however, was less active (IC50, 1.27 microM) than castanospermine (IC50, 0.12 microM) against the mutual target enzyme, cellular alpha-glucosidase I, in a cell-free assay system. The increased effects of MDL 28,574 against alpha glucosidase I in cell culture were attributed to the improved cellular uptake of the more lipophilic derivative. Inhibition of this enzyme activity in HIV infected H9 cells impaired viral glycoprotein processing and resulted in the expression of abnormally configured gp120. This did not affect virus production, but the virions had decreased infectivity which was partially related to a reduced ability to bind to CD4+ T cells. PMID- 7986009 TI - Analysis of genes encoding D-alanine-D-alanine ligase-related enzymes in Enterococcus casseliflavus and Enterococcus flavescens. AB - Using degenerate oligonucleotides complementary to sequences encoding conserved amino acid motifs in D-alanine-D-alanine (Ddl) ligases, we have amplified ca. 600 bp fragments from Enterococcus casseliflavus ATCC 25788 and Enterococcus flavescens CCM439. Sequence analysis of the amplification products indicated that each strain possessed two genes, ddlE. cass. and vanC-2, and ddlE. flav. and vanC 3, respectively, encoding Ddl-related enzymes. The fragments internal to the vanC genes were 98.3% identical. The vanC-2 gene was cloned into Escherichia coli and sequenced. Extensive similarity (66% nucleotide identity) was detected between this gene and vanC-1 from Enterococcus gallinarum (S. Dutka-Malen, C. Molinas, M. Arthur, and P. Courvalin, Gene 112:53-58, 1992), suggesting that the vanC genes are required for intrinsic low-level resistance to vancomycin. The partial deduced amino acid sequences of ddlE. cass. and ddlE. flav. were identical and closely related to that of the Ddl ligase of Enterococcus faecalis (79% identity). In Southern hybridization experiments, only DNA from E. casseliflavus and E. flavescens hybridized to probes internal to the vanC-2 and ddlE. cass. genes. PMID- 7986010 TI - In vitro anti-Mycobacterium avium activities of quinolones: predicted active structures and mechanistic considerations. AB - The relationship between the structures of quinolones and their anti Mycobacterium avium activities has been previously derived by using the Multiple Computer-Automated Structure Evaluation program. A number of substructural constraints required to overcome the resistance of most of the strains have been identified. Nineteen new quinolones which qualify under these substructural requirements were identified by the program and subsequently tested. The results show that the substructural attributes identified by the program produced a successful a priori prediction of the anti-M. avium activities of the new quinolones. All 19 quinolones were found to be active, and 4 of them are as active or better than ciprofloxacin. With these new quinolones, the updated multiple computer-automated structure evaluation program structure-activity relationship analysis has helped to uncover additional information about the nature of the substituents at the C5 and C7 positions needed for optimal inhibitory activity. A possible explanation of drug resistance based on the observation of suicide inactivation of bacterial cytochrome P-450 by the cyclopropylamine moiety has also been proposed and is discussed in this report. Furthermore, we confirm the view that the amount of the uncharged form present in a neutral pH solution plays a crucial role in the drug's penetration ability. PMID- 7986011 TI - Activity of epiroprim (Ro 11-8958), a dihydrofolate reductase inhibitor, alone and in combination with dapsone against Toxoplasma gondii. AB - We examined the effect of epiroprim (Ro 11-8958), a dihydrofolate reductase inhibitor, alone and in combination with dapsone, against Toxoplasma gondii. In vitro, the anti-T. gondii effects of epiroprim and dapsone were observed at nanogram-per-milliliter levels when a 72-h uracil assay and an infection rate of one parasite per 120 macrophages were used. In combination, these drugs exerted a synergistic effect that, however, was only parasitostatic. In a model of acute infection, mice were infected intraperitoneally with 10(4) parasites of the RH strain of T. gondii and were treated for 14 days by gavage (therapy divided into two daily dosages), starting 24 h after infection. Used alone, dapsone and epiroprim, each at a dose of 50 mg/kg of body weight per day, protected 10 and 0% of the mice, respectively. When these drugs were administered simultaneously, a 100% survival rate was observed. Pyrimethamine-sulfadiazine (4 and 250 mg/kg/day, respectively) protected 100% of the mice. A 3-week therapy of chronically infected mice with either epiroprim (50 mg/kg/day), dapsone (50 mg/kg/day), or pyrimethamine (15 mg/kg/day) reduced the numbers of T. gondii cysts and the inflammation in their brains. A combination of epiroprim and dapsone, both at 50 mg/kg/day, further reduced the number of brain cysts in comparison with the number after the corresponding monotherapies. Epiroprim may have a role in the prophylaxis or therapy of human toxoplasmosis, especially when combined with other drugs active against T. gondii, such as dapsone. PMID- 7986012 TI - Neurotoxicity of artemisinin analogs in vitro. AB - The sesquiterpene endoperoxide antimalarial agents arteether and artemether have been reported to cause neurotoxicity with a discrete distribution in the brain stems of rats and dogs after multiple doses. The nature and distribution of the brain lesions suggest a specific neuronal target, the identity of which is unknown. In order to further investigate artemisinin analog-induced neurotoxicity, we evaluated several in vitro models: fetal rat primary neuronal cultures, fetal rat secondary astrocyte cultures, and transformed neuronal cultures (rat-derived neuroblastoma NG108-15 and mouse-derived neuroblastoma Neuro-2a). Results indicate that toxicity was specific for neuronal cell types but not glial cells. Neurotoxicity, as indexed by liberation of lactate dehydrogenase and/or inhibition of radiolabelled-leucine uptake, was seen in all three neuronal culture types, implicating a common target. In vitro neurotoxicity was dose and time dependent. Acute exposure to drug results in delayed, but not immediate, manifestations of cell toxicity. Structure-activity comparisons indicate that substitutions at positions 9 and 10 and stereoisomerism at position 10 of the artemisinin backbone influence the degree of toxicity. The endoperoxide is necessary but not sufficient for toxicity. Sodium artesunate and dihydroartemisinin, a metabolite common to all artemisinin analogs currently being developed for clinical use, are the most potent of all analogs tested. These results are consistent with a specific neuronal target, but the identity of the target(s) remains unknown. PMID- 7986013 TI - Biological activity of amoebicin m4-A from Bacillus licheniformis M-4. AB - Amoebicin m4-A from Bacillus licheniformis M-4 exerts a bactericidal and bacteriolytic action on Bacillus megaterium GR10. Protein, DNA, and RNA synthesis are inhibited, and the membrane electrical potential of this bacterium is depleted by amoebicin. Synthesis of DNA and RNA by Naegleria fowleri HB-1 is also inhibited. Liposomes constructed from L-alpha-phosphatidylcholine become permeable to ions, low-molecular-weight solutes, and high-molecular-weight polymers after treatment with amoebicin. PMID- 7986014 TI - Comparison of mitochondrial morphology, mitochondrial DNA content, and cell viability in cultured cells treated with three anti-human immunodeficiency virus dideoxynucleosides. AB - The toxic effects of various concentrations of 2',3'-dideoxycytidine (ddC), 2',3' dideoxy-2',3'-didehydrothymidine (D4T), and 2',3'-dideoxyinosine (ddI) on CEM cells after 4 days of culture were assessed by measuring cell viability, mitochondrial DNA (mtDNA) content, and mitochondrial morphology. Cell viability and mtDNA content in drug-treated cultures were significantly reduced in a concentration-dependent fashion in comparison with cell viability and mtDNA content in untreated cultures. Cells in the treated cultures also showed significant changes in their mitochondrial morphologies which included distortion and reduction of the cristae and numerous vesicles. Unique features of the morphological changes were associated with each drug. The decrease in cell viability and mtDNA content and the increase in mitochondrial ultrastructural changes were directly related to the concentrations of the drugs used. The potencies of these compounds in reducing cell viability, mtDNA content, and normal mitochondria were in the order ddC > D4T > ddI. Comparison of the three assays used demonstrated that mtDNA content is a significantly more sensitive measure of drug toxicity than cell viability and mitochondrial morphology for the three compounds studied. PMID- 7986015 TI - Effects of peroxides on susceptibilities of Escherichia coli and Mycobacterium smegmatis to isoniazid. AB - Escherichia coli strains were previously found to be susceptible to the antituberculosis drug isonicotinic acid hydrazide (isoniazid [INH]) when they carried certain mutations that also sensitize them to peroxides: a deletion in oxyR, a redox-sensitive regulator of hydrogen peroxide-inducible genes, or mutations in both katG and ahpCF, OxyR-regulated genes encoding hydroperoxidase I, and an alkyl hydroperoxide reductase. To test whether INH, like peroxides, activates OxyR, the effect of INH on OxyR regulation was examined. Primer extension assays showed that transcription of the OxyR-regulated oxyS gene was not significantly induced by INH in wild-type cells, indicating that INH does not activate OxyR. However, the INH-susceptible katG ahpCF mutant strain was found to have constitutively high levels of oxyS transcription. This suggested that the lack of peroxidase expression in these strains allows endogenous oxidants to accumulate, and this leads not only to constitutive OxyR activation but also to INH susceptibility. Consistent with this concept, hydrogen peroxide or cumene hydroperoxide potentiated the INH susceptibilities of wild-type cells, while the antioxidant ascorbic acid protected the susceptible katG ahpCF mutant strain from INH. Superoxide radicals, generated by paraquat, did not enhance the INH susceptibilities of wild-type cells. Hydrogen peroxide also potentiated the INH susceptibilities of susceptible and resistant (katG mutant) Mycobacterium smegmatis strains. Our results suggest that INH is converted to a more active drug by reaction with peroxides and that the INH susceptibilities of enterobacteria and mycobacteria are mechanistically related. PMID- 7986016 TI - Albendazole inhibits Pneumocystis carinii proliferation in inoculated immunosuppressed mice. AB - Albendazole, a benzimidazole derivative widely used for treating helminth infections, was successfully used to treat and prevent development of Pneumocystis carinii pneumonia in transtracheally inoculated immunosuppressed mice. For treatment, 3 weeks postinoculation, albendazole at 300 and 600 mg/kg of body weight per day was administered in food for 3 weeks. For prophylaxis, albendazole was begun on the same day as inoculation at 300 mg/kg/day for 7 days, and then the dose was reduced to 150 mg/kg/day for 35 additional days. With these regimens, albendazole was effective both for treatment and prophylaxis. Both dexamethasone-immunosuppressed and L3T4+ monoclonal antibody-immunosuppressed mouse models were used, and albendazole inhibited P. carinii infection in both. PMID- 7986017 TI - Activities of the benzoxazinorifamycin KRM 1648 and ethambutol against Mycobacterium avium complex in vitro and in macrophages. AB - KRM 1648 is a 4-aminobenzoxazine derivative of rifamycin S with potent in vitro activity against the Mycobacterium avium complex (MAC); the MIC for 90% of 24 MAC isolates from AIDS patients was 0.25 microgram/ml as determined by a radiometric broth macrodilution assay. KRM 1648 was bactericidal for MAC isolates in Middlebrook 7H9 broth, with a reduction in viability of 1 to 4 orders of magnitude over 72 h. In human macrophages, KRM 1648 also was bactericidal, with a reduction of 3 to 4 orders of magnitude in CFU per ml of macrophage lysate at a concentration of 1 microgram/ml; however, the bactericidal activity varied approximately 10-fold among the three MAC serovars tested. In growth medium, ethambutol potentiated the effect of KRM 1648, but this potentiation was modest when tested against MAC in macrophages and also varied between MAC strains. KRM 1648 has potential as an antimycobacterial agent for MAC disease, perhaps in combination with other agents so that the use of lower dosages of KRM 1648 than are needed with other rifamycins may be possible. PMID- 7986018 TI - Activity of KRM 1648 alone or in combination with ethambutol or clarithromycin against Mycobacterium avium in beige mouse model of disseminated infection. AB - Rifamycins are active against slowly growing mycobacteria, such as Mycobacterium tuberculosis and Mycobacterium kansasii, but the majority of rifamycins thus far investigated both in vitro and in vivo are inactive or have only modest activity against the Mycobacterium avium complex (MAC). We investigated the activity of three doses of the semisynthetic benzoxazinorifamycin KRM 1648, alone or in combination with ethambutol or clarithromycin, in beige mice challenged with the MAC strain 101. Our results show the following. (i) KRM 1648 was significantly effective against MAC infection as determined by the reduction of the number of bacteria in the blood, liver, and spleen when administered at doses of 20 and 40 mg/kg of body weight per day but not at 10 mg/kg/day, compared with untreated controls. (ii) KRM 1648 (40 mg/kg/day) administered in combination with ethambutol (100 mg/kg/day) resulted in significant reduction in bacteremia compared with values for untreated controls (P 0.001), KRM 1648 alone (P = 0.019), and ethambutol alone (P = 0.003). Furthermore, the combination of KRM 1648 and ethambutol was associated with a significant decrease of the number of bacteria in the spleen and the liver compared with values for both untreated controls and each drug alone (P < 0.001 for all comparisons). (iii) KRM 1648 (40 mg/kg/day) administered in combination with clarithromycin (200 mg/kg/day) resulted in a significant decrease of the number of bacteria in the blood and the spleen compared with the number for untreated controls (P < 0.001 for all comparisons). In our experience, using MAC 101 as the challenging organism, KRM 1648 is the first the number of bacteria in the blood and spleen compared with the number for untreated controls (P >0.001 for all comparions). In our experience, using MAC 101 as the challenging organism, KRM 1648 is the first rifamycin with significant activity in vivo against MAC infection in beige mice. PMID- 7986019 TI - Kinetics of ofloxacin and its metabolites in cerebrospinal fluid after a single intravenous infusion of 400 milligrams of ofloxacin. AB - Ofloxacin has been reported to diffuse readily into the cerebrospinal fluid (CSF) in subjects with both inflamed and uninflamed meninges. However, with moderately susceptible bacteria, ofloxacin concentrations in CSF may be subtherapeutic after administration of an intravenous (i.v.) dose of 200 mg. For this reason, the kinetics of a higher dose of ofloxacin in CSF was studied with humans. Six patients with occlusive hydrocephalus caused by cerebrovascular diseases who had undergone external ventriculostomy received 400 mg of ofloxacin i.v. over 30 min. Serum and CSF samples were drawn repeatedly. Serum from 12 healthy volunteers was sampled repeatedly after they had received 400 mg of ofloxacin i.v. over 60 min. Ofloxacin, ofloxacin-N-oxide, and N-desmethyl-ofloxacin concentrations were determined by high-pressure liquid chromatography with fluorescence detection. The maximum ofloxacin concentrations in the serum of the patients ranged from 7.36 to 11.6 mg/liter (mean, 9.55 mg/liter), the apparent volume of distribution/body weight was 0.96 to 1.19 liters/kg (mean, 1.11 liters/kg), and the total body clearance was 115 to 280 ml/min (mean, 192 ml/min). In healthy volunteers, the volume of distribution/body weight and the total body clearance were higher and amounted to 1.27 +/- 0.18 liters/kg and 217 +/- 43 ml/min (means +/- standard deviations), respectively. These differences were attributed to the older ages of the patients than the volunteers. In the CSF of patients, maximum concentrations of 1.00 to 2.85 mg/liter (mean, 2.04 mg/liter) were observed 0.5 to 4 h following the completion of the ofloxacin infusion. Ofloxacin elimination from CSF was slightly slower than that from serum (half-lives, 4.33 to 10.02 versus 4.27 to 9.14 h). The overall penetration of ofloxacin into CSF, as expressed by the ratios of the areas under the concentration-curves, amounted to 0.59 to 0.81 (mean, 0.65). The more hydrophilic metabolites ofloxacin-N-oxide and N-desmethyl-ofloxacin passed less readily than ofloxacin into the CSF. In conclusion, the concentrations in CSF attained after a single i.v. infusion of 400 mg of ofloxacin in the absence of meningeal inflammation appear to be high enough to inhibit the growth of most staphylococci and members of the family Enterobacteriaceae, which are often involved in CSF shunt infection. Yet, in view of pharmacodynamic studies suggesting a peak concentration in CSF of at least 10 fold the MIC, the use of ofloxacin for central nervous systems infections is optimal only with highly susceptible pathogens (MIC, less than or equal to 0.12 mg/liter). PMID- 7986020 TI - Reaction of antimalarial endoperoxides with specific parasite proteins. AB - The endoperoxides are a new class of antimalarial agents, of which artemisinin (qinghaosu) is the prototype. We have previously shown that artemisinin is capable of alkylating proteins in model reactions. In the present study, we showed that when Plasmodium falciparum-infected erythrocytes are treated with a radiolabeled antimalarial endoperoxide, either arteether, dihydroartemisinin, or Ro 42-1611 (arteflene), the radioactivity is largely coverted into a form which can be extracted with sodium dodecyl sulfate (SDS). Autoradiograms of SDS polyacrylamide gels showed that six malarial proteins are radioactively labeled by the three endoperoxides. This labeling occurs at physiological concentrations of drug and is not stage nor strain specific. The labeled proteins were not the most abundant proteins seen on Coomassie-stained gels. No proteins were labeled when uninfected erythrocytes were treated with these drugs, nor when infected erythrocytes were treated with the inactive analog deoxyarteether. Thus, the antimalarial endoperoxides appear to react with specific malarial proteins. PMID- 7986021 TI - Pneumocystis carinii is resistant to imidazole antifungal agents. AB - Because Pneumocystis carinii is closely related to fungi, drugs useful for treating mycoses have been considered for use in the treatment of P. carinii pneumonia. Six antifungal imidazole drugs were tested for their activities against P. carinii in a short-term culture screen and in animals. None of the imidazoles tested was effective in inoculated infected rats, and only miconazole showed slight effects in culture at the high concentration of 10 micrograms/ml. Analysis of cell membranes from culture-grown P. carinii showed that ergosterol, the target for this class of antifungal agents, was absent, so that the lack of effect of these agents is rational. PMID- 7986022 TI - Efficacy of azithromycin as a causal prophylactic agent against murine malaria. AB - The efficacy of the newly marketed azalide azithromycin was compared with that of the clinical agent doxycycline in a murine model of sporozoite-induced malaria. Drug was administered once; Plasmodium yoelii sporozoites were administered 2 h later; survival at day 60 was determined. For parenterally administered drug, 160 mg of azithromycin or doxycycline per kg of body weight was 100% effective; 40 mg of azithromycin per kg was 80% effective, but 40 mg of doxycycline per kg was 40% effective. Orally administered azithromycin was somewhat less effective than parenterally administered drug, consistent with the 37% clinical oral bioavailability of this agent. For orally administered azithromycin, 160 mg/kg was 100% effective and 40 mg/kg was 40% effective. The efficacy of azithromycin in comparison with that of doxycycline and the known prolonged levels of azithromycin in the livers of humans suggest that azithromycin has potential as a clinical causal prophylactic agent for malaria. PMID- 7986023 TI - Efficacy of 2'-deoxy-2'-fluororibosides against influenza A and B viruses in ferrets. AB - Single-dose treatments (5 to 40 mg/kg of body weight given intraperitoneally) of ferrets with 2'-deoxy-2'-fluoroguanosine or its prodrug, 2,6-diamino-purine-2' fluororiboside, 1 h after infection with influenza A virus significantly inhibited replication of virus in the upper respiratory tract, resulting in amelioration of fever and nasal inflammation. Replication of virus in the lower respiratory tract was also reduced > 100-fold, but three doses were required to prevent replication in the lungs. In ferrets infected with influenza B virus, single-dose treatment (40 mg/kg given intraperitoneally) produced a similar but reduced response in comparison with that in ferrets infected with influenza A virus, indicating that dosing was not optimal for this virus. PMID- 7986024 TI - Bactericidal activities of DU-6859a and clinafloxacin (CI-960) against staphylococci. AB - Time killing curves were calculated at concentrations of 2 and 8 times the MICs of DU-6859a and clinafloxacin against six isolates of Staphylococcus aureus. Both quinolones produced a decrease in the log10 CFU per milliliter of > or = 3 within 3 h at 2 and 8 times the MIC for the ciprofloxacin-susceptible isolates and at 8 times the MIC for the ciprofloxacin-resistant isolates; however, only 8 times the MIC of DU-6859a consistently prevented regrowth of all isolates after 24 h of incubation. PMID- 7986025 TI - Treatment of severe pneumonia with ciprofloxacin or imipenem. PMID- 7986026 TI - Production and release of polyphosphate by a genetically engineered strain of Escherichia coli. AB - A recombinant strain of Escherichia coli MV1184, which contains plasmid-borne genes encoding the phosphate-specific transport (Pst) system and polyphosphate (polyP) kinase, accumulated high levels of Pi and released polyP into the medium. PolyP could be separated from the culture supernatant by DEAE-Toyopearl 650M chromatography and identified by high-resolution 31P nuclear magnetic resonance spectroscopy. Once E. coli recombinants accumulated high levels of polyP, they released polyP concomitantly with Pi uptake. PolyP release did not accompany the decrease in the cell density, indicating that it is not simply a result of cell lysis. PolyP release ceased when Pi became depleted in the medium and resumed upon addition of Pi to the medium. When Pi uptake was inhibited by 0.1 mM carbonyl cyanide m-chlorophenylhydrazone (CCCP), no polyP release was observed. Furthermore, neither Pi uptake nor polyP release occurred when cells were incubated at 4 degrees C. These findings suggest that the occurrence of polyP release is a possible mechanism that limits a further increase in the cellular polyP concentration in E. coli recombinants. High-resolution 31P nuclear magnetic resonance spectroscopy also detected a surface pool of polyP in intact cells of the E. coli recombinant. The polyP resonance increased when cells were treated with EDTA and broadened upon the addition of a shift reagent, praseodymium. Although the mechanism of surface polyP accumulation is unclear, surface polyP seems to serve as the source for polyP release. PMID- 7986027 TI - Construction from a single parent of baker's yeast strains with high freeze tolerance and fermentative activity in both lean and sweet doughs. AB - From a freeze-tolerant baker's yeast (Saccharomyces cerevisiae), 2,333 spore clones were obtained. To improve the leavening ability in lean dough of the parent strain, we selected 555 of the high-maltose-fermentative spore clones by using a method in which a soft agar solution containing maltose and bromocresol purple was overlaid on yeast colonies. By measuring the gassing power in the dough, we selected 66 spore clones with a good leavening ability in lean dough and a total of 694 hybrids were constructed by crossing them. Among these hybrids, we obtained 50 novel freeze-tolerant strains with good leavening ability in all lean, regular, and sweet doughs comparable to that of commercial baker's yeast. Hybrids with improved leavening ability or freeze tolerance compared with the parent yeast and commercial baker's yeasts were also obtained. These results suggest that hybridization between spore clones derived from a single parent strain is effective for improving the properties of baker's yeasts. PMID- 7986028 TI - Role of Na+ in transport of Hg2+ and induction of the Tn21 mer operon. AB - The effects of sodium ions on the uptake of Hg2+ and induction of the Tn21 mer operon were studied by using Escherichia coli HMS174 harboring the reporter plasmids pRB28 and pOS14. Plasmid pRB28 carries merRT', and pOS14 carries merRTPC of the mer operon, both cloned upstream of a promoterless luciferase gene cassette in pUCD615. The bioluminescent response to 1 microM Hg2+ was significantly inhibited in E. coli HMS174(pRB28) in minimal medium supplemented with sodium ions at 10 to 140 mM. After initial acceleration, light emission declined at 50 nM Hg2+ in the presence of Na+. The mer-lux assay with resting cells carrying pRB28 and 203Hg2+ uptake experiments showed increased induction and enhanced mercury uptake, respectively, in media supplemented with sodium ions. The presence of Na+ facilitated maintenance of bioluminescence in resting HMS174(pRB28) cells induced with 50 nM Hg2+. External K+ stimulated bioluminescent response in HMS174(pRB28) and HMS174(pOS14) grown in sodium phosphate minimal medium devoid of potassium ions. Sodium ions appear to facilitate mercury transport. We propose that sodium-coupled transport of mercuric ions can be one of the mechanisms for mercury uptake by E. coli and that the Na+ gradient may energize the transport of Hg2+. PMID- 7986029 TI - Identification and purification of a protein that induces production of the Lactobacillus acidophilus bacteriocin lactacin B. AB - Lactacin B is a heat-stable bacteriocin produced by Lactobacillus acidophilus N2 that is active against closely related lactobacilli, including Lactobacillus delbrueckii subsp. lactis (formerly Lactobacillus leichmannii) ATCC 4797. Pure producer cultures propagated in MRS broth (initial pH 6.5) contain no lactacin B; it is detected only in cultures maintained at pH 5.0 to 6.0 and produced optimally at pH 6.0 S. F. Barefoot and T. R. Klaenhammer, Antimicrob. Agents Chemother. 26:328-334, 1984). Associative growth of producer and indicator, L. delbrueckii subsp. lactis ATCC 4797, resulted in production of an inhibitor identical to lactacin B. Associative growth increased lactacin B production from nondetectable levels (< 100 activity units [AU]/ml) to between 3,200 and 6,400 AU/ml in MRS broth (initial pH 6.5) and resulted in early but equal production of lactacin B (approximately 25,600 AU/ml) in broth maintained at pH 6.0. Indicator cells, but not spent culture filtrates, induced lactacin B production. Indicator cells disrupted by a French pressure cell yielded cell-free filtrates containing inducing activity. Chromatofocusing and gel filtration high-performance liquid chromatography of cell-free filtrates yielded a protein with a pI of 4.1 and a molecular size of approximately 58 kDa that induced lactacin B production. Analytical isoelectric focusing yielded a single protein band. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis gels contained a 28-kDa protein suggesting a two-subunit structure. Protein sequencing identified an N-terminal serine and 18 additional amino acids. To our knowledge, there are not previous descriptions of proteins that induce bacteriocin production in lactic acid bacteria. PMID- 7986031 TI - Monoclonal antibodies with a high degree of specificity for Listeria monocytogenes serotype 4b. AB - Strains of Listeria monocytogenes serotype 4b account for a large fraction of sporadic listeriosis cases, as well as all major food-borne epidemics attributed to this pathogen. We have identified a set of three monoclonal antibodies which showed a high degree of specificity for strains of L. monocytogenes serotype 4b. Two of these antibodies (c74.33 and c74.180, isotypes immunoglobulin M [IgM] and IgG3, respectively) recognized all serotype 4b strains, whereas antibody c74.22 (isotype IgG1) failed to recognize certain epidemic-associated strains. The corresponding antigens were located on the surface of the bacteria and were expressed following bacterial growth in different media and over a wide range of temperatures (4, 22, and 37 degrees C). Heating L. monocytogenes cells at 80,90, or 100 degrees C abolished reactivity for c74.22 but not for c74.33 MAb. These MAbs were negative for all of the non-Listeria strains tested, including representatives of several gram-negative and gram-positive species. The surface antigen recognized by c74.22 appeared to be associated with the ability of the bacteria to enter (invade) mammalian cells in culture. PMID- 7986030 TI - Development of an amylolytic Lactobacillus plantarum silage strain expressing the Lactobacillus amylovorus alpha-amylase gene. AB - An amylolytic Lactobacillus plantarum silage strain with the starch-degrading ability displayed by Lactobacillus amylovorus was developed. An active fragment of the gene coding for alpha-amylase production in L. amylovorus was cloned and integrated into the chromosome of the competitive inoculant strain L. plantarum Lp80 at the cbh locus. The alpha-amylase gene fragment was also introduced into L. plantarum Lp80 on an autoreplicative plasmid. Both constructions were also performed in the laboratory strain L. plantarum NCIB8826. All four recombinant strains secreted levels of amylase ranging from 23 to 69 U/liter, compared with 47 U/liter for L. amylovorus. Secretion levels were higher in L. plantarum NCIB8826 than in L. plantarum Lp80 derivatives and were higher in recombinant strains containing autoreplicative plasmids than in the corresponding integrants. The L. plantarum Lp80 derivative containing the L. amylovorus alpha-amylase gene fragment integrated into the host chromosome secreted alpha-amylase to a level comparable to that of L. amylovorus and was stable over 50 generations of growth under nonselective conditions. It grew to a higher cell density than either the parent strain or L. amylovorus in MRS medium containing a mixture of starch and glucose as the fermentable carbohydrate source. This recombinant alpha-amylolytic L. plantarum strain would therefore seem to have considerable potential as a silage inoculant for crops such as alfalfa, in which water-soluble carbohydrate levels are frequently low but starch is present as an alternative carbohydrate source. PMID- 7986032 TI - Antibody-direct epifluorescent filter technique for rapid, direct enumeration of Escherichia coli O157:H7 in beef. AB - Artificially inoculated Escherichia coli O157:H7 was directly enumerated in ground beef and beef exudate, without enrichment or selection, by the antibody direct epifluorescent filter technique (Ab-DEFT). The total assay time of the Ab DEFT was less than 1 h. The beef was homogenized, treated for 15 min with trypsin and Triton X-100, and passed through a 5-microns-pore-size prefilter and then through a 0.2-microns-pore-size black polycarbonate filter. The final filter was stained directly with fluorescein-labeled anti-O157 polyclonal antibody, rinsed, and examined by epifluorescence microscopy. The sensitivity of the Ab-DEFT was compared with that of a standard enrichment culture technique. Both methods reliably determined the presence of the pathogen in beef at 16 CFU/g. The Ab-DEFT was also useful for quantifying the pathogen and monitoring its growth in beef. PMID- 7986033 TI - Influence of preadsorbed milk proteins on adhesion of Listeria monocytogenes to hydrophobic and hydrophilic silica surfaces. AB - The adsorption of beta-lactoglobulin, bovine serum albumin, alpha-lactalbumin, and beta-casein for 8 h and beta-lactoglobulin and bovine serum albumin for 1 h at silanized silica surfaces of low and high hydrophobicity, followed by incubation in buffer and contact with Listeria monocytogenes, resulted in different numbers of cells adhered per unit of surface area. Adhesion to both surfaces was greatest when beta-lactoglobulin was present and was lowest when bovine serum albumin was present. Preadsorption of alpha-lactalbumin and beta casein showed an intermediate effect on cell adhesion. Adsorption of beta lactoglobulin for 1 h resulted in a generally lower number of cells adhered compared with the 8-h adsorption time, while the opposite result was observed with respect to bovine serum albumin. The adhesion data were explainable in terms of the relative rates of arrival to the surface and postadsorptive conformational change among the proteins, in addition to the extent of surface coverage in each case. PMID- 7986034 TI - In vivo monitoring system for structure-function relationship analysis of the antibacterial peptide apidaecin. AB - A unique antibacterial peptide derivative found in immune honeybee lymph, apidaecin 1b (AP1), was randomly mutagenized and characterized by a newly established system to analyze in vivo its structure-function relationship. Initially, a high-level expression host-vector system for AP1 in Escherichia coli was constructed by creating a fusion protein with the highly stable Streptomyces subtilisin inhibitor (SSI) molecule. Expression of the SSI-AP1 fusion protein was found to depend on the concentration of the transcriptional inducer isopropyl beta-D-thio-galactopyranoside (IPTG) and to parallel the degree of growth inhibition of the transformant cells. Subsequently, apidaecin derivatives produced by localized random mutagenesis were screened with this IPTG concentration-controlled in vivo system by monitoring the growth inhibition patterns of the transformant cells. One mutant apidaecin (P9L) that had reduced activity was purified and isolated from the periplasmic fraction of an E. coli transformant. Its antibacterial activity was reduced to one-third of that of wild type apidaecin. When considered together with the other mutations, it was concluded that several Pro residues, including that at the ninth position, are responsible for expression of the antibacterial action of apidaecin. PMID- 7986035 TI - Methionine uptake and cytopathogenicity of viable but nonculturable Shigella dysenteriae type 1. AB - A pathogenic strain of Shigella dysenteriae type 1 was selected for study to elucidate the physiology and potential pathogenicity of organisms in the viable but nonculturable (VBNC) state in the environment. Studies in our laboratory have shown that S. dysenteriae type 1 survives in laboratory microcosms in the VBNC state for long periods of time, i.e., more than 6 months. VBNC cells of S. dysenteriae type 1 were found to retain cytopathogenicity for cultured HeLa cells. To determine whether VBNC S. dysenteriae type 1 expressed protein after loss of culturability, 35S-labelled methionine was added to suspensions of VBNC cells. Total cellular proteins were extracted and examined by autoradiography. Results indicate that VBNC S. dysenteriae type 1 is capable of both active uptake of methionine and incorporation of methionine into protein. Amino acid uptake and protein synthesis substantiate the viability of cells of S. dysenteriae type 1 in the VBNC state, i.e., although the cells are unable to be cultured on laboratory media by standard bacteriological methods, the cells remain metabolically active. Furthermore, VBNC cells of S. dysenteriae type 1 may pose a potential public health hazard that has not yet been recognized. PMID- 7986036 TI - Stabilization and rational design of serine protease AprM under highly alkaline and high-temperature conditions. AB - Rational shift of the optimum pH toward alkalinity and enhancement of thermostability were investigated by using a thermostable extremely alkaline protease (optimum pH, 12 to 13) from the alkaliphilic and thermophilic Bacillus sp. strain B18'. The protease gene (aprM) was cloned, and the sequence analysis revealed an open reading frame of 361 amino acids that was composed of a putative signal sequence (24 amino acids), a prosequence (69 amino acids), and a mature enzyme (268 amino acids) (molecular weight, 27,664). The amino acid sequence of this protease was compared with those of other serine proteases. A direct correlation of higher optimum pH with an increase in the number of arginine residues was observed. An even more thermostable mutant enzyme was created by introducing a point mutation. When the position of the beta-turn, Thr-203, was replaced by Pro, the residual activity of this mutant enzyme at 80 degrees C for 30 min was higher than that of the wild-type enzyme (50% versus 10%). The specific activity of this mutant enzyme at 70 degrees C was 105% of that of the wild-type enzyme under nondenaturation condition. These data suggest that the higher content of Arg residues favors the alkalinity of the serine protease and that introduction of a Pro residue into the beta-turn structure stabilizes the enzyme. PMID- 7986037 TI - Electroporation of Alcaligenes eutrophus with (mega) plasmids and genomic DNA fragments. AB - Electroporation was used as a tool to explore the genetics of the heavy-metal resistant strain Alcaligenes eutrophus CH34. A 12.9-kb A. eutrophus-Escherichia coli shuttle vector, pMOL850, was constructed to optimize electroporation conditions. This vector is derived from the E. coli plasmid pSUP202 and contains the replication region of the A. eutrophus megaplasmid pMOL28. Electroporation was used to transform A. eutrophus CH34 derivatives with megaplasmids (sizes up to 240 kb), and transformants were selected for resistance to heavy metals. Electroporation was also performed with endonuclease-digested genomic DNA. Transformation of markers affecting lysine biosynthesis (lysA194) and biosynthesis of the siderophore alcaligin E were observed. Transfer of the nonselected markers pheB332 and aro-333, linked to lysA194, confirmed the intervention of homologous recombination. However, during transformation of ale::Tn5-Tc, illegitimate recombination and transposition were also observed as an alternative for the inheritance of the Tn5-Tc markers. PMID- 7986038 TI - The NodD proteins of Rhizobium sp. strain BR816 differ in their interactions with coinducers and in their activities for nodulation of different host plants. AB - The early steps of symbiotic nodule formation by Rhizobium spp. on plants require coordinate expression of several nod gene operons, which is accomplished by the activating protein NodD. Rhizobium sp. strain BR816, isolated from Leucaena leucocephala, contains four nodD genes which differ in their interaction with flavonoids. Two of the four NodD proteins, namely, NodD1 and NodD2, obey the LysR rule regarding the need of a coinducer. NodD3 shows hardly any inducing activity, and NodD4 contains a high basal activity and no response to any of the flavonoids tested. Complementation experiments with the NGR234 nodD mutant by the different nodD genes of BR816, as well as the analysis of the nodulation phenotype of different nodD mutants of BR816, revealed that all the nodD genes of BR816 are functional, but differences can be noticed when different host plants are tested. Whereas the nodD2 and nodD4 genes of BR816 have a great impact on the nodulation of L. leucocephala, nodD3 and nodD4 appear to be important for the nodulation of Phaseolus vulgaris. It appears that NodD1 of BR816 can function as a transcriptional activator in bean nodulation but not in nodulation of L. leucocephala. PMID- 7986039 TI - Degradation of methyl bromide by methanotrophic bacteria in cell suspensions and soils. AB - Cell suspensions of Methylococcus capsulatus mineralized methyl bromide (MeBr), as evidence by its removal from the gas phase, the quantitative recovery of Br- in the spent medium, and the production of 14CO2 from [14C]MeBr. Methyl fluoride fluoride (MeF) inhibited oxidation of methane as well as that of [14C]MeBr. The rate of MeBr consumption by cells varied inversely with the supply of methane, which suggested a competitive relationship between these two substrates. However, MeBr did not support growth of the methanotroph. In soils exposed to high levels (10,000 ppm) of MeBr, methane oxidation was completely inhibited. At this concentration, MeBr removal rates were equivalent in killed and live controls, which indicated a chemical rather than biological removal reaction. At lower concentration (1,000 ppm) of MeBr, methanotrophs were active and MeBr consumption rates were 10-fold higher in live controls than in killed controls. Soils exposed to trace levels (10 ppm) of MeBr demonstrated complete consumption within 5 h of incubation, while controls inhibited with MeF or incubated without O2 had 50% lower removal rates. Aerobic soils oxidized [14C]MeBr to 14CO2, and MeF inhibited oxidation by 72%. Field experiments demonstrated slightly lower MeBr removal rates in chambers containing MeF than in chambers lacking MeF. Collectively, these results show that soil methanotrophic bacteria, as well as other microbes, can degrade MeBr present in the environment. PMID- 7986040 TI - Metabolic activity of pathogenic bacteria during semicontinuous anaerobic digestion. AB - In natural environments such as anaerobic digesters, bacteria are frequently subjected to the stress of nutrient fluxes because of the continual changes in the flow of nutrients, and to survive, they must be capable of adapting readily to nutrient changes. In this study, the metabolic activities of Escherichia coli, Salmonella typhimurium, Yersinia enterocolitica, Listeria monocytogenes, and Campylobacter jejuni were studied within culture bags (Versapor-200 filters, 0.22 microns pore size) in laboratory anaerobic digesters. The metabolic activity of these bacteria was indicated by their adenylate energy charge (EC) ratios and their ability to incorporate [3H]thymidine, which was related to the respective changes in viable numbers within the culture bags during anaerobic digestion. Fluctuations in the adenylate EC ratios, the uptake of [3H]thymidine, and the viable numbers of E. coli, S. typhimurium, Y. enterocolitica, and L. monocytogenes cells were probably due to constant changes in the amount of available nutrients within the anaerobic digesters. The viability of S. typhimurium increased quickly after a fresh supply of nutrients was added to the system as indicated by the uptake of [3H]thymidine and an increase in the adenylate EC ratios. The viable numbers of E. coli, S. typhimurium, Y. enterocolitica, and L. monocytogenes organisms declined rapidly from 10(7) to 10(8) CFU/ml to 10(3) to 10(4) CFU/ml and remained at this level for an indefinite period. The decimal reduction time calculated during the period of exponential decline ranged from 0.8 to 1.2 days for these bacteria. C. jejuni had the greatest mean decimal reduction time value (3.6 days).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7986041 TI - Detection of hepatitis A virus, rotavirus, and enterovirus in naturally contaminated shellfish and sediment by reverse transcription-seminested PCR. AB - A reverse transcription-PCR method was developed to detect enterovirus (EV), hepatitis A virus (HAV), and rotavirus (RV) RNAs in shellfish and sediment. The method was first tested under experimental conditions by using virus-spiked shellfish to evaluate assay sensitivity. The use of CC41 cellulose was found to be efficient for removing inhibitors of RV detection. For sediment samples, a Sephadex column was used to allow the detection of EV and HAV RNAs. The specificity of amplified products was controlled by hybridization with digoxigenin-labeled oligoprobes. The method was then applied to naturally contaminated shellfish and sediments. EV, HAV, and RV RNAs were detected in 22, 14, and 20% of the shellfish samples, respectively. No relationship between viral contamination and bacterial contamination was found. When viral RNAs (HAV or EV) were detected in sediments, they were also detected in shellfish. PMID- 7986042 TI - Cloning and heterologous expression of a gene encoding an alkane-induced extracellular protein involved in alkane assimilation from Pseudomonas aeruginosa. AB - Pseudomonas aeruginosa PG201 produces a 16-kDa extracellular protein in media containing n-hexadecane as a carbon source but not in media containing glycerol or glucose. This protein was purified, and the N-terminal amino acid sequence was determined. The amino acid composition of the protein was found to be very similar to that of the so-called protein-like activator for n-alkane oxidation (PA) from P. aeruginosa S7B1. This extracellular protein was previously characterized (K. Hisatsuka, T. Nakahara, Y. Minoda, and K. Yamada, Agric. Biol. Chem. 41:445-450, 1977) and found to stimulate the growth of P. aeruginosa on n hexadecane and to possess emulsifying activity. To study the role(s) of the PA protein and to make it accessible for possible future applications, we have cloned the PA-encoding (pra) gene and determined its nucleotide sequence. This analysis revealed a protein-coding region of 162 amino acids, with the first 25 residues being reminiscent of those of a typical bacterial signal sequence. The pra gene was inactivated by insertional mutagenesis, and the resulting strain was found to lack extracellular PA protein and to be retarded in its growth in n hexadecane-containing media. These results are consistent with the growth stimulatory role of the PA protein. The pra gene was expressed in Escherichia coli, and substantial amounts of the recombinant protein were found in the extracellular growth medium. The recombinant protein was purified by metal chelate affinity chromatography. The ability to produce secreted PA protein by E. coli provides a simple and safe means to analyze its function(s) in alkane assimilation in the future. PMID- 7986043 TI - Survival of enteric viruses on environmental fomites. AB - The survival of human enteric viruses on several porous (paper and cotton cloth) and nonporous (aluminum, china, glazed tile, latex, and polystyrene) environmental surfaces has been evaluated. Viruses persisted for extended periods on several types of materials commonly found in institutions and domestic environments. The stability of the viruses was generally influenced by environmental factors such as relative humidity (RH), temperature, and the type of surface contaminated. Overall, hepatitis A virus (HAV) and human rotavirus (HRV) were more resistant to inactivation than enteric adenovirus (ADV) and poliovirus (PV). The resistance to the desiccation step appears to be of major significance in determining the survival of a virus dried on fomites. ADV and PV showed a pronounced decrease in titer at this stage, whereas HAV and HRV displayed little decay at the desiccation step. HAV and HRV persistence was not affected by the presence of fecal material. On nonporous surfaces, PV and ADV persisted better in the presence of feces. However, on porous fomites the presence of fecal material had a negative influence on the survival of PV and ADV. Except for HRV, greater virus survival was observed at 4 degrees than at 20 degrees C. PV and HAV survival was enhanced at high RH; the survival of the latter was enhanced at least for nonporous materials. When dried on porous materials, HRV also exhibited greater persistence at high RH. The survival of ADV was not affected by RH. The validity of using bacteriophages of Bacteroides fragilis as indicators of human viruses dried on fomites was evaluated.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7986044 TI - Effects of ruminal protozoa on cellulose degradation and the growth of an anaerobic ruminal fungus, Piromyces sp. strain OTS1, in vitro. AB - An anaerobic rumen fungus, Piromyces sp. strain OTS1, was incubated in the presence or absence of a mixed, A-type, protozoal population obtained from a goat, in a medium containing filter paper cellulose as energy source and antibiotics to suppress bacterial growth. Fermentation end products, cellulose degradation, and chitin as an indicator of fungal biomass were examined. In the presence of protozoa, total volatile fatty acids, notably propionate and butyrate, increased, and lactate decreased. In fungus-protozoan coincubations, formate was not detected at the end of the experiment and the amount of reducing sugars remained low throughout the incubation period. The fungal growth in the coincubations was negatively affected. While protozoal predation on zoospores was one mechanism of inhibition, mature fungal cells were also affected. Total cellulose degradation was greater in fungal monocultures, but the amount of cellulose degraded per unit of fungal biomass was 25% larger in the coincubations. The negative effects that the protozoal predatory activity had on the fungal growth and subsequently on the amount of cellulose degraded by Piromyces sp. strain OTS1 were partially attenuated by the protozoal fibrolytic activity or by an enhanced fungal activity due to a more favorable environment. PMID- 7986045 TI - Stoichiometric flux balance models quantitatively predict growth and metabolic by product secretion in wild-type Escherichia coli W3110. AB - Flux balance models of metabolism use stoichiometry of metabolic pathways, metabolic demands of growth, and optimality principles to predict metabolic flux distribution and cellular growth under specified environmental conditions. These models have provided a mechanistic interpretation of systemic metabolic physiology, and they are also useful as a quantitative tool for metabolic pathway design. Quantitative predictions of cell growth and metabolic by-product secretion that are experimentally testable can be obtained from these models. In the present report, we used independent measurements to determine the model parameters for the wild-type Escherichia coli strain W3110. We experimentally determined the maximum oxygen utilization rate (15 mmol of O2 per g [dry weight] per h), the maximum aerobic glucose utilization rate (10.5 mmol of Glc per g [dry weight] per h), the maximum anaerobic glucose utilization rate (18.5 mmol of Glc per g [dry weight] per h), the non-growth-associated maintenance requirements (7.6 mmol of ATP per g [dry weight] per h), and the growth-associated maintenance requirements (13 mmol of ATP per g of biomass). The flux balance model specified by these parameters was found to quantitatively predict glucose and oxygen uptake rates as well as acetate secretion rates observed in chemostat experiments. We have formulated a predictive algorithm in order to apply the flux balance model to describe unsteady-state growth and by-product secretion in aerobic batch, fed batch, and anaerobic batch cultures. In aerobic experiments we observed acetate secretion, accumulation in the culture medium, and reutilization from the culture medium. In fed-batch cultures acetate is cometabolized with glucose during the later part of the culture period.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7986046 TI - Evaluation of counting error due to colony masking in bioaerosol sampling. AB - Colony counting error due to indistinguishable colony overlap (i.e., masking) was evaluated theoretically and experimentally. A theoretical model to predict colony masking was used to determine colony counting efficiency by Monte Carlo computer simulation of microorganism collection and development into CFU. The computer simulation was verified experimentally by collecting aerosolized Bacillus subtilis spores and examining micro- and macroscopic colonies. Colony counting efficiency decreased (i) with increasing density of collected culturable microorganisms, (ii) with increasing colony size, and (iii) with decreasing ability of an observation system to distinguish adjacent colonies as separate units. Counting efficiency for 2-mm colonies, at optimal resolution, decreased from 98 to 85% when colony density increased from 1 to 10 microorganisms cm-2, in contrast to an efficiency decrease from 90 to 45% for 5-mm colonies. No statistically significant difference (alpha = 0.05) between experimental and theoretical results was found when colony shape was used to estimate the number of individual colonies in a CFU. Experimental colony counts were 1.2 times simulation estimates when colony shape was not considered, because of nonuniformity of actual colony size and the better discrimination ability of the human eye relative to the model. Colony surface densities associated with high counting accuracy were compared with recommended upper plate count limits and found to depend on colony size and an observation system's ability to identify overlapped colonies. Correction factors were developed to estimate the actual number of collected microorganisms from observed colony counts.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7986047 TI - Detection of Pseudomonas aeruginosa from clinical and environmental samples by amplification of the exotoxin A gene using PCR. AB - PCR was used to detect Pseudomonas aeruginosa from water samples by amplifying a 396-bp region of the exotoxin A (ETA) structural gene sequence. The identify of the amplified 396-bp fragment was confirmed by digesting it with PvuI restriction endonuclease, which produced the predicted 246- and 150-bp fragments. Specific primers amplified ETA-positive P. aeruginosa DNA, whereas other species of Pseudomonas and GC-rich bacteria did not yield any 396-bp fragment. The specificity and sensitivity of the assay were 100 and 96%, respectively, which confirms the assay's reliability for diagnostic and epidemiological studies. The assay can detect as few as 5 to 10 cells in a 10-ml water sample or 0.1 pg of P. aeruginosa DNA per reaction mixture (5 microliters) by ethidium bromide staining of an agarose gel. Ten-times-lower concentrations were detected by hybridization with a digoxigenin-labeled oligonucleotide probe internal to the PCR product. With this PCR method, ETA-positive P. aeruginosa was detected in animal cage water samples at a level of 40 cells per ml. This method is rapid and less cumbersome than other diagnostic methods for the identification of P. aeruginosa strains. The method described can be used to detect a low level of P. aeruginosa from environmental and clinical samples without the use of selective media or additional biochemical tests. PMID- 7986048 TI - A conditional suicide system in Escherichia coli based on the intracellular degradation of DNA. AB - The potential risks associated with the intentional or unintentional release of genetically engineered microorganisms led to the construction of biological containment systems by which bacteria are killed in a controlled suicide process. In previously published suicide systems, cell killing was caused by proteins destroying the cell membrane or cell wall. Here a conditional cell killing system based on the intracellular degradation of cellular DNA is presented. The nuclease gene used was that of the extracellular nuclease of Serratia marcescens. The nuclease gene was deleted for the leader-coding sequence, and the truncated gene was put under the control of the lambda pL promoter. Following thermoinduction of the nuclease gene cassette in Escherichia coli, cell survival dropped to 2 x 10( 5), and more than 80% of the radioactively labeled DNA was converted to acid soluble material within 2.5 h in the absence of cell lysis. The majority (84%) of clones which survived thermoinduced killing turned out to be as sensitive to a second thermoinduction as the original strain. The other clones showed somewhat slower killing kinetics or slightly higher final levels of survivors. The suicide system described combines the regulated killing of cells with the destruction of intracellular DNA otherwise potentially available for horizontal gene transfer processes. PMID- 7986049 TI - Cloning of the aapT gene and characterization of its product, alpha-amylase pullulanase (AapT), from thermophilic and alkaliphilic Bacillus sp. strain XAL601. AB - A thermophilic and alkaliphilic Bacillus sp. strain, XAL601, was isolated from soil. It produces a thermostable and alkaline-stable enzyme with both alpha amylase and pullulanase activities. The alpha-amylase-pullulanase gene (aapT) from this Bacillus strain was cloned, and its nucleotide sequence was determined (GenBank accession number D28467). A very large open reading frame composed of 6,096 bases, which encodes 2,032 amino acid residues with an M(r) of 224,992, was found. The deduced amino acid sequence revealed that the four highly conserved regions that are common among amylolytic enzymes were well conserved. These include an active center and common substrate-binding sites of various amylases. In the C-terminal region, a six-amino-acid sequence (Gly-Ser-Gly-Thr-Thr-Pro) is repeated 12 times. The aapT gene was then subcloned in Escherichia coli and overexpressed under the control of the lac promoter. Purification of AapT from this recombinant E. coli was performed, and it was shown that the aapT gene product exhibits both alpha-amylase and pullulanase activities with one active site. The optimum temperature and pH for enzyme activity were found to be 70 degrees C and pH 9, respectively. Furthermore, AapT was found to strongly adsorb to crystalline cellulose (Avicel) and raw corn starch. Final hydrolyzed products from soluble starch range from maltose (G2) to maltotetraose (G4). Only maltotriose (G3) was produced from pullulan. The enzyme also hydrolyzes raw starch under a broad range of conditions (60 to 70 degrees C and pH 8 to 9). PMID- 7986050 TI - Isolation and characterization of Linocin M18, a bacteriocin produced by Brevibacterium linens. AB - Brevibacterium linens M18, isolated from red smear cheese, produces a substance that inhibits the growth of Listeria spp. and several coryneform and other gram positive bacteria. No gram-negative bacteria were inhibited. The substance is heat labile, sensitive to proteolytic enzymes, and stable between pH 3 and 12. High levels of this bacteriocin, named Linocin M18, were obtained in the stationary growth phase. Linocin M18 was purified by ultrafiltration, ultracentrifugation, and gel filtration chromatography. In its native form, it is a proteinaceous aggregate with a high molecular weight. Fractions with Linocin M18 activity contained particles of 20 to 30 nm in diameter. The bacteriocin consists of a single protein subunit with a molecular mass of 31 kDa and an isoelectric point of 4.5 N-terminal sequence analysis yielded Met-Asn-Asn-Leu-Tyr Arg-Glu-Leu-Ala-Pro-Ile-Pro-Gly-Pro-Ala-Ala-Ala-Glu- Ile. Significant homology with published sequences was lacking. PMID- 7986051 TI - Alfalfa yield response to inoculation with recombinant strains of Rhizobium meliloti with an extra copy of dctABD and/or modified nifA expression. AB - The construction of rhizobial strains which increase plant biomass under controlled conditions has been previously reported. However, there is no evidence that these newly constructed strains increase legume yield under agricultural conditions. This work tested the hypothesis that carefully manipulating expression of additional copies of nifA and dctABD in strains of Rhizobium meliloti would increase alfalfa yield in the field. The rationale for this hypothesis is based on the positive regulatory role that nifA plays in the expression of the nif regulon and the fact that a supply of dicarboxylic acids from the plant is required as a carbon and energy source for nitrogen fixation by the Rhizobium bacteroids in the nodule. These recombinant strains, as well as the wild-type strains from which they were derived, are ideal tools to examine the effects of modifying or increasing the expression of these genes on alfalfa biomass. The experimental design comprised seven recombinant strains, two wild type strains, and an uninoculated control. Each treatment was replicated eight times and was conducted at four field sites in Wisconsin. Recombinant strain RMBPC-2, which has an additional copy of both nifA and dctABD, increased alfalfa biomass by 12.9% compared with the yield with the wild-type strain RMBPC and 17.9% over that in the uninoculated control plot at the site where soil nitrogen and organic matter content was lowest. These increases were statistically significant at the 5% confidence interval for each of the three harvests made during the growing season. Strain RMBPC-2 did increase alfalfa biomass at the Hancock site; however, no other significant increases or decreases in alfalfa biomass were observed with the seven other recombinant strains at that site. At three sites where this experiment was conducted, either native rhizobial populations or soil nitrogen concentrations were high. At these sites, none of the recombinant strains affected yield. We conclude that RMBPC -2 can increase alfalfa yields under field conditions of nitrogen limitation, low endogenous rhizobial competitors, and sufficient moisture. PMID- 7986053 TI - Immobilization of Escherichia coli expressing the lux genes of Xenorhabdus luminescens. AB - The luxCDABE operon of Xenorhabdus luminescens was cloned into pUC18 to make pLITE27. Expression of the lux genes from the lac promoter resulted in strong constitutive light emission by Escherichia coli DH5 carrying the recombinant lux plasmid, pLITE27. When strain DH5(pLITE27) was immobilized with sodium alginate CaCl2, the embedded cells retained their luminescence up to 2 weeks under appropriate storage conditions. PMID- 7986052 TI - Sensitization of heat-treated Listeria monocytogenes to added lysozyme in milk. AB - Listeria monocytogenes was highly resistant to hen egg white lysozyme in whole milk but was sensitive in media and in phosphate buffer. Methods to sensitize the pathogen to lysozyme in milk were investigated. Treatment of whole milk by cation exchange to remove minerals, particularly Ca2+ and Mg2+, slightly promoted inactivation of L. monocytogenes by lysozyme at 4 degrees C over a period of 6 days. Heat treatment (62.5 degrees C for 15 s) strongly sensitized L. monocytogenes to lysozyme in demineralized milk and in MES [2-(N morpholino)ethanesulfonic acid] buffer. Addition of Ca2+ or Mg2+ to the demineralized milk restored resistance to lysozyme. Cells were more rapidly heat inactivated at 55 degrees C in demineralized milk containing lysozyme, and addition of Ca2+ to the demineralized milk restored the resistance to heat. The results indicate that minerals or mineral-associated components protect L. monocytogenes from inactivation by lysozyme and heat in milk, probably by increasing cell surface stability. The heat treatment of foods containing added lysozyme can probably play a significant role in producing microbiologically safe foods. PMID- 7986054 TI - Decreased susceptibility of melanized Cryptococcus neoformans to UV light. AB - Melanized Cryptococcus neoformans cells were less susceptible than nonmelanized cells to the fungicidal effects of UV light. Phenoloxidase-catalyzed production of melanin-like pigments may serve to protect the fungus against ionizing radiation. PMID- 7986055 TI - A transcriptional reporter for in vivo promoter analysis in the archaeon Haloferax volcanii. AB - We have used a modified intron-containing tRNA(Pro(UGG) gene (tRNA(ProM), derived from the Saccharomyces cerevisiae tRNA(Pro(UGG) gene, as a reporter to measure in vivo transcription from a halophilic archaeon promoter. Coupling of the yeast tRNA(ProM) gene to the Haloferax volcanii tRNA(Lys) promoter on the H. volcanii plasmid pWL201 led to the production of a single stable transcript that was readily quantitated by Northern (RNA) blot analysis. Comparison of tRNA(ProM) RNA production from constructs containing the wild-type tRNA(Lys) promoter and those containing mutant tRNA(Lys) promoters demonstrated that this assay system can be used to measure expression from strong and weak promoters. PMID- 7986056 TI - Glucose uptake by Listeria monocytogenes Scott A and inhibition by pediocin JD. AB - Glucose uptake by Listeria monocytogenes Scott A was inhibited by the bacteriocin pediocin JD and by the protonophore carbonyl cyanide m-chlorophenyhydrazone. Experiments with monensin, nigericin, chlorhexidine diacetate, dinitrophenol, and gramicidin, however, showed that glucose uptake could occur in the absence of a proton motive force. L. monocytogenes cell extracts phosphorylated glucose when phosphoenolpyruvate (PEP) was present in the assay mixture, and whole cells incubated with 2-deoxyglucose accumulated 2-deoxyglucose-6-phosphate, indicating the presence of a PEP-dependent phosphotransferase system in this organism. Glucose phosphorylation also occurred when ATP was present, suggesting that a proton motive force-mediated glucose transport system may also be present. We conclude that L. monocytogenes Scott A accumulates glucose by phosphotransferase and proton motive force-mediated systems, both of which are sensitive to pediocin JD. PMID- 7986057 TI - Identification of a heroin esterase in Rhodococcus sp. strain H1. AB - A strain of a Rhodococcus sp. (termed H1) capable of utilizing heroin as its sole carbon and energy source was isolated by selective enrichment. An inducible heroin esterase was partially purified and shown to catalyze the hydrolysis of both of the acetylester groups of heroin. The enzyme displays optimum activity at pH 8.5 and appears to be a trimer of identical subunits with an M(r) or 39,000 and a native M(r) of 120,000. PMID- 7986058 TI - Production of beauvericin by a strain of Fusarium proliferatum isolated from corn fodder for swine. AB - Beauvericin, a cyclodepsipeptide, was produced by cultures of three strains of Fusarium proliferatum, M-5991, M-6992, and M-6993, grown on cracked corn. M-5991 produced approximately 1,000-mg/kg levels of fumonisins, moniliformin, and beauvericin. PMID- 7986059 TI - Pertinence of indicator organisms and sampling variables to Vibrio concentrations. AB - Vibrio-indicator relationships and effects of day, depth, and tidal levels on the density of vibrios enumerated by the most probable number technique were investigated. Counts of vibrios taken monthly from Apalachicola Bay, Fla., were either negatively correlated or showed no correlation with counts of indicator bacteria (Escherichia coli, enterococci, fecal coliforms, and total coliforms). Water samples collected on two days from the surface and bottom over a complete tidal cycle on each day were analyzed for differences in vibrio concentrations. Concentrations of vibrios in samples taken on different days, in those taken at different depths, and in those taken at different tidal levels were significantly different, indicating that these factors need to be taken into account in health related studies. PMID- 7986060 TI - Evaluation of alternariol and alternariol methyl ether for mutagenic activity in Salmonella typhimurium. AB - Alternariol and alternariol methyl ether were tested in the Ames Salmonella typhimurium assay, and both were shown, with and without metabolic activation, to be nonmutagenic to strains TA98 and TA100. The finding of other investigators that alternariol methyl ether is weakly mutagenic to TA98 without metabolic activation could have resulted from the presence of a small amount of one of the highly mutagenic altertoxins in the alternariol methyl ether originally tested. PMID- 7986061 TI - Phagocyte-generated superoxide reduces Fe3+ to displace it from the surface of asbestos. AB - Injury after exposure to mineral oxide dusts is considered to be mediated by free radical generation. In vitro production of hydroxyl radical by a fibrous silicate increases with the [Fe3+] complexed to the dust surface. The study hypothesis tested was that extracellular fluids and phagocytic cells can decrease concentrations of iron complexed to the surface of a fibrous silicate by employing host chelators and reductants. Such a depletion of surface [Fe3+] would predict decrements in both oxidant generation and the resultant injury after inhalation and instillation of these mineral oxides. Crocidolite (2.0 mg) which was exposed to either 5.0 ml rat plasma or 10.0 ml rat lavage fluid for 1 h had diminished surface [Fe3+]. Similarly, incubations of crocidolite (2.0 mg) with either 10.0 ml rat alveolar macrophages (1.0 x 10(6) cells/ml) or 10.0 ml rat neutrophils (1.0 x 10(7) cells/ml) decreased concentrations of surface iron. In vivo exposures of asbestos contained in chambers allowing or precluding inflammatory cell entry revealed that the influx of phagocytes was associated with greater decreases in surface [Fe3+]. The body chelators transferrin and lactoferrin were unable to extract the metal from fiber surface in vitro. However, superoxide generated by phagocytes did displace the iron from the crocidolite surface. We conclude that extracellular fluids and phagocytic cells have a capacity to diminish [Fe3+] complexed to the surface of asbestos and therefore decrease the potential for oxidative stress and injury to a living system after exposure to these dusts.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7986062 TI - Studies on the reversibility of protein S-thiolation in human endothelial cells. AB - Exposure of human umbilical vein endothelial cells to oxidants, such as hydrogen peroxide and diamide, has been shown to induce protein-specific S-thiolation of cellular proteins. In this study we have now identified glutathione (reduced form) as the major low molecular-weight thiol that is bound to protein substrates in human umbilical vein endothelial (HUVE) cells during oxidative stress and investigated the dose- and time-response relationship of diamide- and hydrogen peroxide-induced 8-thiolation of HUVE cell protein. Intact HUVE cells are able to rapidly reduce S-thiolated proteins with almost quantitative reappearance of reduced glutathione in the cells and protection from acute, lytic cytotoxicity. Additionally, studies were performed with detergent-solubilized cell extracts to determine the nature of the reductants operating in HUVE cells to maintain protein thiol homeostasis. The results clearly show the involvement of NADH- and NADPH-dependent systems. These data suggest that the reversible S-thiolation of proteins in these human endothelial cells may represent a significant cellular antioxidant and regulatory mechanism during oxidative stress. PMID- 7986063 TI - Catechol adrenergic agents enhance hydroxyl radical generation in xanthine oxidase systems containing ferritin: implications for ischemia/reperfusion. AB - Iron chelators have been reported to protect tissues against reperfusion injury. This implies that iron is being released into the plasma or is made accessible in tissues for oxidation-reduction reactions. It has been postulated that ferritin is a likely source for this iron. This report demonstrates that adrenergic agents with the catechol structure, which includes the endogenous catecholamines norepinephrine and epinephrine, are capable of releasing iron from ferritin. It is shown that the net release of iron from ferritin by epinephrine is significantly enhanced under anaerobic conditions. The findings suggest that catecholamines can mediate iron release from ferritin under conditions that can occur during ischemia/reperfusion. Catecholamines are also shown to interact with the released iron and xanthine oxidase to produce highly reactive hydroxyl radicals. The implications of this interaction for ischemia/reperfusion are discussed. PMID- 7986064 TI - Involvement of preexisting lipid hydroperoxides in Cu(2+)-stimulated oxidation of low-density lipoprotein. AB - Oxidative modification of human low-density lipoprotein (LDL) is thought to play an important role in the development of atherosclerosis. LDL oxidizability is believed to be strongly influenced by factors such as (a) content of preexisting lipid hydroperoxides (LOOHs) and (b) content of endogenous antioxidants such as alpha-tocopherol and beta-carotene. The purpose of this study was to examine the prooxidant role of preexisting LDL-LOOHs, using a recently developed method for ultrasensitive and selective LOOH analysis: high-performance liquid chromatography with mercury drop electrochemical detection (HPLC-EC). Exceedingly low detection limits for LDL-LOOHs have been achieved by HPLC-EC, e.g., approximately 100 fmol for cholesteryl ester hydroperoxide (CEOOH). This sensitivity has allowed us to monitor LDL-LOOHs at levels that are undetectable by most other methods. Fresh LDL prepared with the utmost care to prevent autoxidation was found to contain small, yet significant amounts of CEOOH, 6-12 pmol/mg protein. Our data suggest that these peroxides could not have arisen during LDL isolation or sample work-up for HPLC-EC. Incubation with GSH and phospholipid hydroperoxide glutathione peroxidase resulted in nearly complete reduction of the CEOOH. This LDL was found to be much more resistant to Cu(2+) induced peroxidation than starting material, exhibiting a lag period that was at least six times greater. We have also determined that LDL becomes progressively more susceptible to Cu(2+)-induced lipid peroxidation (as evidenced by a shortened lag) when it is preloaded with increasing amounts of photochemically generated LOOHs. Taken together, these results provide strong support for the idea that preexisting LOOHs in LDL are important determinants of its overall oxidizability. PMID- 7986065 TI - Tartrate dehydrogenase-oxalate complexes: formation of a stable analog of a reaction intermediate complex. AB - Oxalate has been shown to form a stable complex with Mn-tartrate dehydrogenase NADH complexes which are proposed to mimic an intermediate formed during catalytic turnover. The formation of this complex can be detected under turnover conditions, where oxalate acts as a time-dependent inhibitor, and under equilibrium conditions, where oxalate binding triggers a slow protein conformation change detectable by fluorescence spectroscopy. Both the rate constant for the change in fluorescence intensity upon oxalate binding and the magnitude of the fluoresence change show a hyperbolic dependence on oxalate concentration. The time-dependent inhibition by oxalate is not consistent with a model in which oxalate binds to enzyme-NAD; rather, it is proposed that inhibition arises from binding to enzyme-NADH. The apparent dissociation constants of oxalate from enzyme-NAD+ and the enzyme-NADH complexes are 80 and 1 microM, respectively. The fluorescence changes which accompany oxalate binding are suggested to arise from a protein conformational change which serves to sequester reactants in the active site. Consistent with this hypothesis, it was observed that although some alternative pyridine nucleotide cofactors supported the multistep tartrate dehydrogenase-catalyzed net nonoxidative decarboxylation of meso-tartrate only at drastically reduced rates, none of the intermediate hydroxypyruvate was released into solution. In addition, fluorescence anisotropy measurements were conducted to investigate the mode of NADH binding. PMID- 7986066 TI - Characterization of flavocytochrome C552 from the thermophilic photosynthetic bacterium Chromatium tepidum. AB - A M(r) 68 kDa flavocytochrome c552 has been isolated from the thermophilic photosynthetic purple sulfur bacterium Chromatium tepidum and shown to consist of a M(r) 25 kDa subunit that contains two covalently bound heme c and a M(r) 43 kDa subunit that probably contains a single FAD. The prosthetic group content, absorbance spectra, and subunit composition of the C. tepidum flavocytochrome are quite similar to those previously reported for the flavocytochrome c552 isolated from a mesophilic Chromatium species, Chromatium vinosum. The oxidation-reduction properties of the hemes present in the C. tepidum flavocytochrome have been characterized by titrations, the effect of temperature on the catalytic activity of the protein has been investigated, and the heme environment has been characterized using resonance Raman spectroscopy. PMID- 7986067 TI - The role of oxalate in lignin peroxidase-catalyzed reduction: protection from compound III accumulation. AB - Reduction may be an important step in the degradation of some highly oxidized environmental pollutants by Phanerochaete chrysosporium. Lignin peroxidases (LiP) from P. chrysosporium are able to catalyze reductive reactions using veratryl alcohol (VA) as a mediator and either oxalate or EDTA as electron donors. Reduction of oxygen to superoxide, monitored by oxygen consumption, was used as a measure of the reductive activity of LiP. In the presence of EDTA, the rate of O2 reduction catalyzed by LiP decreased with time and increasing concentrations of H2O2. When oxalate replaced EDTA, LiP-catalyzed O2 reduction did not decrease with time, and increasing concentrations of H2O2 increased the duration and extent of O2 reduction. LiP was converted to the compound III state in the presence of EDTA, H2O2, and veratryl alcohol. When oxalate replaced EDTA, compound II was observed. The importance of the veratryl alcohol cation radical (VA.+) in the conversion of LiP compound III to active enzyme has been previously examined (D.P. Barr and S.D. Aust, 1994, Arch. Biochem. Biophys. 311, 378-382). We propose that rapid reduction of VA.+ by EDTA results in accumulation of LiP compound III and the loss of activity resulting in a decrease in LiP-catalyzed reduction reactions. Oxalate is less effective in reducing the VA.+, therefore, some VA.+ remains to convert compound III to active enzyme and maintain LiP catalyzed reduction reactions. Thus oxalate, a normal secondary metabolite of P. chrysosporium, is a suitable candidate for mediating reduction reactions by LiP in vivo. PMID- 7986068 TI - Alternate splicing of human thromboxane synthase mRNA. AB - Two species of human thromboxane synthase (TXS) cDNA, called TXS-I and -II, were previously isolated (K. Ohashi, K.-H. Ruan, R. J. Kulmacz, K. K. Wu, and L.-H. Wang, 1992, J. Biol. Chem. 267, 789-793). TXS-II differs from TXS-I by a 163-bp deletion near the 3'-end of the coding region. Both types of TXS mRNA have now been demonstrated to be present in various blood and lung cultured cells. Analysis of the exon-intron boundaries of TXS genomic DNA revealed that the two mRNAs are generated via alternate splicing: TXS-II is produced by skipping an entire 163-bp exon which encodes the polypeptide segment containing the heme binding cysteine conserved among other P450s. The mechanism by which alternate splicing occurs is probably due to the presence of a more powerful potential as the 3' acceptor site in the intron following the 163-bp exon. When expressed in baculovirus system, recombinant TXS-I catalyzed the formation of thromboxane A2 and 12-hydroxyheptadecatrienoic acid (HHT), whereas recombinant TXS-II did not synthesize thromboxane A2 or HHT. Alternate splicing of TXS RNA transcript thus may provide a mechanism for limiting cellular biosynthesis of thromboxane A2. PMID- 7986069 TI - Ah receptor in different tissues of C57BL/6J and DBA/2J mice: use of competitive polymerase chain reaction to measure Ah-receptor mRNA expression. AB - A competitive polymerase chain reaction (PCR) method was used to determine the Ah receptor mRNA content in several tissues of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-sensitive C57BL/6J and less susceptible DBA/2J mice. Total RNA from liver, lung, thymus, spleen, heart, kidney, brain, muscle, and placenta was isolated and reverse-transcribed. Each cDNA was coamplified with a known amount of homologous competitor fragment, and PCR products were quantified by extrapolating against a standard curve. The Ah-receptor mRNA was expressed in all tissues examined. The highest mRNA level was found in lung, yielding concentrations of 31.7 +/- 11.0 X 10(3) molecules/100 ng RNA and 20.3 +/- 8.9 X 10(3) molecules/100 ng RNA in C57BL/6J and DBA/2J mice, respectively. In heart, liver, thymus, brain, and placenta the Ah-receptor mRNA content was about 5-10 times lower than in lung. Low levels were found in spleen, kidney, and muscle. Statistical analysis of the data revealed no significant differences regarding the Ah-receptor mRNA expression between C57BL/6J and DBA/2J mice. From these results it is suggested that factors other than differences in Ah-receptor mRNA content may be responsible for different susceptibility of C57BL/6J and DBA/2J mice toward TCDD. PMID- 7986070 TI - Development of an in vitro model for investigating the formation of the nuclear Ah receptor complex in mouse Hepa 1c1c7 cells. AB - An in vitro assay for investigating factors which modulate formation of the nuclear aryl hydrocarbon (Ah) receptor complex was developed using 9S cytosolic Ah receptor isolated from wild-type Hepa 1c1c7 cells treated with 2,3,7,8 [3H]tetrachlorodibenzo-p-dioxin (TCDD) at 4 degrees C and nuclei from Ah responsive and -nonresponsive wild-type and mutant Hepa 1c1c7 cells. Incubation of the radiolabeled ([3H]TCDD) 9S cytosolic Ah receptor with nuclei from untreated wild-type Ah-responsive mouse Hepa 1c1c7 cells resulted in a time- and temperature-dependent formation of the nuclear Ah receptor complex as determined by either velocity sedimentation analysis or gel mobility shift assays using a consensus 32P-labeled dioxin-responsive element. Maximal levels of the nuclear Ah receptor formed within 30 min at 37 degrees C and significantly lower levels were observed after incubation at 4, 15, or 25 degrees C. Complementation studies using nuclei from untreated wild-type and Ah-nonresponsive class II mutant (translocation-deficient) cells and radiolabeled 9S cytosolic receptor (bound with [3H]TCDD) from both wild-type and mutant cell lines were also carried out. The results indicated that nuclear translocation was primarily inhibited using cytosol from mutant cells confirming the requirement for the aryl hydrocarbon receptor nuclear translocator protein for formation of the nuclear Ah receptor complex. The effects of a series of Ah receptor antagonists, ATP, vanadate apyrase, phosphatases, and lectin WGA, on formation of the nuclear Ah receptor complex were also investigated in the in vitro model using radiolabeled cytosolic Ah receptor and nuclei from untreated wild-type Hepa 1c1c7 cells.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7986071 TI - Selenocysteine tRNA and serine tRNA are aminoacylated by the same synthetase, but may manifest different identities with respect to the long extra arm. AB - Selenocysteine (Sec) tRNA([Ser])Sec donates Sec to protein, but interestingly, this amino acid is synthesized on tRNA which is first aminoacylated with serine. Thus, the identity elements in tRNA([Ser])Sec for aminoacylation correspond to elements for seryl-tRNA synthetase recognition. As tRNA([Ser])Sec has low homology to the tRNA(Ser) isoacceptors, it would seem then that the identity elements in tRNA([Ser])Sec involve (1) very specific sequences, (2) conformational features, and/or (3) different points or domains for tRNA[Ser]Sec:synthetase and tRNASer:synthetase recognition. Initially, we confirmed that the same synthetase aminoacylates both tRNAs by showing that a mutant tRNA[Ser]Sec which has a blocked 3'-terminus is a competitive inhibitor of tRNASer aminoacylation with a partially purified and a highly purified seryl-tRNA synthetase preparation. The discriminator base (base G73) is essential for aminoacylation of tRNA([Ser])Sec and tRNA(Ser), while the long extra arm plays an important role which seems to be orientation- and length-specific in tRNA(Ser) and, in addition, may manifest sequence specificity in tRNA([Ser])Sec. This difference in the tRNA recognition specificity is discussed. The acceptor stem, DHU stem, and T phi C stem contribute to the recognition process, but to a lesser extent than the discriminator base and the long extra arm. PMID- 7986072 TI - Glucose-induced phosphorylation of the MDH2 isozyme of malate dehydrogenase in Saccharomyces cerevisiae. AB - The cytosolic isozyme of malate dehydrogenase, MDH2, was previously shown to be subject to rapid inactivation and proteolysis following the addition of glucose to yeast cultures growing on nonfermentable carbon sources. In this report, we show that MDH2 is phosphorylated during the process of glucose-induced degradation. A truncated active form of MDH2 lacking the first 12 residues of the amino terminus was previously found to be resistant to glucose-induced degradation and, as shown in this study, is not subject to phosphorylation. Site directed mutagenesis was conducted to change Ser-12 in the authentic enzyme to Ala-12 and to Asp-12. The S12A substitution has little effect on glucose-induced phosphorylation and degradation, whereas the enzyme with the S12D substitution is subject to phosphorylation and inactivation but not to rapid degradation. This provides clear evidence that inactivation is not simply a result of degradation. Additional mutagenesis was conducted to change His-214, a critical active site residue, to Leu-214. Analysis of expression of full-length and truncated forms of the H214L enzyme demonstrated that catalytic inactivity is not a prerequisite for degradation and confirmed an essential role for the amino terminus of the authentic enzyme in this phenomenon. PMID- 7986073 TI - Catalysis of the oxidation and reduction reactions of steroid and stilbene estrogens by nuclear enzymes. AB - We demonstrated for the first time that nuclei were able to convert a stilbene estrogen (diethylstilbestrol) to reactive metabolites, which covalently bind to nuclear proteins and DNA. Depending on the cofactor used, nuclear enzymes catalyzed oxidation and/or reduction of stilbene and steroid estrogens. 2 Hydroxyestradiol (a major metabolite of steroidal estrogen, 17 beta-estradiol) and diethylstilbestrol (DES) were oxidized to 2,3-estradiol quinone and DES quinone, respectively, by peroxide-supported nuclear cytochromes P450. A Lineweaver-Burk plot of rate of formation of DES quinone at various substrate concentrations yielded a Km = 15 microM and Vmax = 10 nmol/mg protein/min. The oxidation of DES to DES quinone by nuclei was drastically decreased by known inhibitors of cytochromes P450. DES quinone was reduced back to DES by nuclei in the presence of NADPH, presumably through cytochrome P450 reductase. The reduction of DES quinone to DES by nuclei was significantly inhibited by antibodies and inhibitors of cytochrome P450 reductase. Under reaction conditions similar to oxidation of DES to DES quinone by nuclei, it was observed that nuclear metabolic products of DES were able to covalently bind to nuclear proteins and DNA. The data reported here establish that DES and a catechol estrogen can be oxidized to quinones and that the quinones may be reduced back to the hydroquinones by nuclear preparations when fortified with an appropriate cofactor and that reactive intermediates are involved based on observed covalent binding to macromolecules. The significance of these events, and their possible role in toxicity/cancer/teratogenicity, however, is not at all clear. PMID- 7986074 TI - Investigation of the active site of the cyanogenic beta-D-glucosidase (linamarase) from Manihot esculenta Crantz (cassava). II. Identification of Glu 198 as an active site carboxylate group with acid catalytic function. AB - The broad-specificity cyanogenic beta-D-glucosidase (beta-D-glucoside glucohydrolase, EC 3.2.1.21) (linamarase) from Manihot esculenta Crantz (cassava) was irreversibly inactivated by N-bromoacetyl-beta-D-glucopyranosylamine according to pseudo-first-order kinetics with a second-order efficiency constant (ki/Ki = 0.1 min-1 M-1) identical for p-nitrophenyl-beta-D-glucopyranosidase, p nitrophenyl-beta-D-galactopyranosidase, and linamarase activities of the enzyme. The competitive inhibitor p-nitrothiophenyl-beta-D-glucopyranoside protected the enzyme from inactivation. pH dependence of the pseudo-first-order rate constant of inactivation revealed the involvement of an amino acid side chain in the inactivation process with pKa 7.0, which is very similar to that of the acid catalyst group of the enzyme (pKE2 = 7.2). The involved amino acid, which has to be ionized for the inactivation, was identified as Glu-198 using 14C-labeled inactivator to label the enzyme, cleaving the labeled protein into peptides and then purifying and sequencing the labeled peptide. This residue is highly conserved in the homologous family A beta-glucosidases and family A1-A5 cellulases and lies in a consensus Asn-Glu-Pro motif occurring in all of these enzymes. PMID- 7986075 TI - Demonstration of glutathione peroxidase in rat liver peroxisomes and its intraorganellar distribution. AB - Earlier, we reported that rat liver peroxisomes contain Cu-Zn superoxide dismutase (J. Biol. Chem. 267, 6870), thereby suggesting a new antioxidant role for this organelle in free radical metabolism. In this study, we report for the first time that mammalian peroxisomes also contain glutathione peroxidase. Using highly purified rat liver peroxisomes isolated by Nycodenz gradient, we found that peroxisomes contain glutathione peroxidase which shows enzymatic activity with different substrates such as hydrogen peroxide, cumene hydroperoxide, and t butyl hydroperoxide. This activity could be inhibited in vitro by mercaptosuccinate. Western blot analysis revealed that peroxisomes from control and ciprofibrate-treated livers show immunoreactive bands with antibodies raised against glutathione peroxidase. The intraperoxisomal distribution of glutathione peroxidase was investigated by using peroxisomal membrane and matrix proteins. The results revealed that glutathione peroxidase is a matrix enzyme. The presence of glutathione peroxidase in peroxisomes provides an alternate enzyme system responsible for the degradation of organic peroxides and the degradation of H2O2 under conditions in which catalase is inactivated (e.g., ischemia-reperfusion and endotoxemia). These findings suggest that glutathione peroxidase in peroxisomes may play a novel role in the cellular antioxidant responses to various oxidative stress conditions. PMID- 7986076 TI - Endocytosis and recycling of gangliosides in a human melanoma cell line: inhibitory effect of brefeldin A and monensin. AB - The internalization and recycling of glycosphingolipids (GLs), added exogenously to cells, has been shown in a number of systems. In addition, a portion of the internalized GLs becomes elongated by further glycosylation, presumably by passage through the Golgi apparatus, and is recycled to the plasma membrane. We have previously shown (K. Furukawa, I. Thampoe, H. Yamaguchi, and K. O. Lloyd J. Immunol. 142, 848, 1989) that NeuGc-LacCer (GM3), added exogenously to cultured human melanoma cells, is converted to NeuAc-NeuGc-LacCer (GD3) and appears at the cell surface where it can be recognized by a monoclonal antibody (32-27M) specifically recognizing this structure. The mechanism of this process has been investigated by analyzing the effect of monensin and Brefeldin A (BFA), two drugs known to affect vesicular transport and Golgi function, on the recycling of NeuGc LacCer. Using two different serological assays, BFA was shown to specifically inhibit the recycling process. BFA probably achieves this effect by inhibiting the transfer of endocytosed GL from endosomes and the trans Golgi network to the Golgi stacks by a retrograde route and thus prevents its entry into the biosynthetic compartments. Monensin had a similar, but less clear-cut, effect on GM3 recycling. These results have important implications for understanding the modulation of cell surface glycolipids. PMID- 7986077 TI - Purification of a phenobarbital-inducible morphine UDP-glucuronyltransferase isoform, absent from Gunn rat liver. AB - A morphine UDP-glucuronyltransferase (morphine UGTPB) was purified from liver microsomes of Sprague-Dawley rats treated with phenobarbital. UDP-glucuronyl transferases in the liver microsomes were solubilized with Emulgen 911 and separated by omega-(beta-carboxypropionyl-amino)octyl Sepharose 4B column chromatography, which has been developed in our laboratory. Morphine UDP glucuronyltransferases were eluted into two fractions, Peak I and Peak II, which have different substrate specificities. Morphine UGTPB was purified by two times of Chromato-focusing from Peak II which was more specific to morphine. The purified morphine UGTPB gave an apparent pI of 8.0 on chromatofocusing and displayed a subunit molecular weight of 55 kDa after sodium dodecyl sulfate polyacrylamide gel electrophoresis. The purified enzyme catalyzed the glucuronidation of 3-hydroxyl group of morphine and small extent of 4 hydroxybiphenyl, but not of androsterone, bilirubin, chloramphenicol, codeine, 4 methylumbelliferone, 4-nitrophenol, testosterone, and 6-hydroxyl group of morphine. The N-terminal amino acid sequences of morphine UGTPB were identical to those of UGT1*01P which is deficient to homozygous Gunn rat. Peak II was absent from the fraction of omega-(beta-carboxypropionylamino)octyl Sepharose 4B column chromatography of liver microsomes of Gunn rats treated with phenobarbital, whereas morphine UGT in Peak I was PB-inducible in Gunn rats. Present results suggest that an isoform of morphine UDP-glucuronyltransferase belongs to the UGT1 family and is phenobarbital-inducible. PMID- 7986079 TI - Sheep uterus dual lipoxygenase in the synthesis of 14,15-leukotrienes. AB - Lipoxygenase was purified to homogeneity from sheep uterus cytosol using a combination of ion exchangers, ammonium sulfate fractionation, and gel filtration. The purified enzyme was found to be a homodimeric protein with monomer molecular weight of 66 kDa. When incubated with arachidonic acid, the enzyme showed two lipoxygenase activities producing both 12- and 15-HPETEs at the optimum pH of 5.5. The relative concentration of 12- and 15-HETEs, however, changed with the pH of the reaction, 12-HETE being higher in the alkaline range and 15-HETE being higher in the acidic range. Furthermore the enzyme showed the expected dual lipoxygenase based 14,15-LTA4 synthase activity as evidenced by the formation of 8,15-diHETEs, the hydrolysis products of 14,15-LTA4. Isolation of 14,15-LTC4 from the homogenates of sheep uterus gave further evidence on the formation of leukotrienes. This is the first report of the formation of 14,15 series leukotrienes in mammalian reproductive tissue. PMID- 7986078 TI - Cyclic-AMP-dependent protein kinase activity is not required by parathyroid hormone to stimulate phosphoinositide signaling in chondrocytes but is required to transduce the hormone's proliferative effect. AB - Parathyroid hormone (PTH), an activator of both cAMP and phosphoinositide (PI) signaling in growth plate chondrocytes (GPCs), is generally believed to trigger each of these pathways through interactions with separate G proteins. Recently, however, activation of cAMP-dependent protein kinase (pkA) has been found to cause a stimulation of the PI cascade in hepatocytes. This finding raises the possibility that PTH stimulation of PI metabolism in GPCs may really be a secondary event, mediated through a primary stimulation of pkA. Experiments discussed in the present report indicate that the PTH stimulation of PI metabolism in GPCs is independent of pkA activity. The data show that (1) unlike the Ca2+ response evoked by PTH, the responses evoked by dibutyryl-cAMP or Sp diastereomer of cyclic adenosine-3',5'-monophosphothioate, two activators of pkA, require an extracellular Ca2+ source; (2) also unlike PTH, activation of pkA by these same cAMP analogs does not cause an increase in cellular inositol-1,4,5 trisphosphate; and (3) specific inhibition of pkA with N-[2-(p bromocinnamylamino)ethyl]-5-isoquinolinsulfanomide (H-89) or Rp diastereomer of cyclic adenosine-3',5'-monophosphothioate (Rp cAMPS) has no effect on the ability of PTH to evoke its normal Ca2+ response. Furthermore, data presented indicate that the PTH stimulation of GPC proliferation does not require Ca2+ signals, but rather is at least partially dependent on pkA. The data show that either loading the cells with the Ca2+ buffer bis-(o-aminophenoxy)ethane-N,N,N',N'-tetracetic acid or depleting the cells of intracellularly stored Ca2+ is without effect on the stimulation of DNA synthesis by the hormone. Inhibition of pkA activity with H-89 or Rp-cAMPS, in contrast, leads to a significant reduction in the ability of PTH to stimulate its proliferative effect. PMID- 7986080 TI - Glutamine transport in normal and acidotic rat kidney mitochondria. AB - Glutamine transport in both normal and acidotic rat kidney mitochondria was investigated using both isotopic techniques and by spectroscopic measurements in which glutamine metabolism was allowed to occur. Widely used criteria for demonstrating the occurrence of carrier-mediated transport were successfully applied in both cases. Three transport mechanisms were found to occur, namely glutamine uniport, active only during acidosis and glutamine/glutamate and glutamine/malate antiports, active in both normal and acidotic mitochondria. Efflux of glutamate, via a glutamate/OH- translocator, following glutamine uptake by mitochondria was experimentally ruled out. Glutamine uniport in acidotic mitochondria and glutamine/glutamate and glutamine/malate antiports in both normal and acidotic mitochondria were investigated in detail: differences found in Km and Vmax values, in pH and temperature dependence, and in the pattern of inhibitor sensitivity of glutamine transport demonstrated the existence of five different translocators whose activities were found to fit with the physiological requirements of renal ammoniogenesis. PMID- 7986081 TI - Insertion of hydrophilic amino acid residues in the signal peptide/membrane anchor domain of neprilysin (neutral endopeptidase-24.11) results in its cleavage: role of the position of insertion. AB - We have expressed in COS-1 cells mutants of neprilysin (neutral endopeptidase 24.11; NEP) in which the hydrophilic sequence S-Q-N-S was either substituted for V42-T-M-I or inserted after T38 in the signal peptide/membrane anchor (SA) domain. These mutations were introduced in full-length NEP (mutants NEP(H1) and NEP(H2), respectively) and a form of NEP lacking its cytosolic tail (mutants NEP delta cyto(H1) and NEP delta cyto(H2), respectively). Immunoblotting showed that NEP(H1) was membrane-bound while NEP delta cyto(H1), NEP(H2), and NEP delta cyto(H2) were secreted. Furthermore, carbonate treatment of isolated intracellular membranes suggested that cleavage of the SA domain was performed in the endoplasmic reticulum, presumably by signal peptidase. Sequencing of the secreted proteins indicated that cleavage of the SA domain mostly occurred at the carboxy side of Ala46 but also at the carboxy side of Ala41 in NEP(H2) and NEP delta cyto(H2). We conclude that the position of the S-Q-N-S sequence influences the accessibility of the cleavage site and, in the case of NEP(H1) and NEP(H2), the efficiency of cleavage of the SA domain. PMID- 7986082 TI - Glucose-induced oscillations of Ba2+ in pancreatic beta-cells occur without involvement of intracellular mobilization. AB - Ba2+ was used as a substitute for Ca2+ in analyzing the mechanisms responsible for glucose-induced Ca2+ oscillations in pancreatic beta-cells. The 340/380-nm fluorescence excitation ratio was recorded in individual mouse beta-cells loaded with the indicator fura-2. In 3 mM glucose, Ba2+ entered the cell in a concentration-dependent manner and was partially extruded when the ion was removed from the medium. The extrusion of Ba2+ from the beta-cell was dependent on external Na+, suggesting that Ba2+ can substitute for Ca2+ in Na+/Ca2+ countertransport. When extracellular Ba2+ was kept between 0.3 and 0.5 mM, large amplitude oscillations (0.1-0.4 min-1) were induced by glucose at concentrations above 7 mM. The oscillations were often transformed into a sustained elevation either by increase of the glucose or Ba2+ concentrations or by the additions of glucagon, forskolin, or carbachol. Although Ba2+ could substitute for Ca2+ in the glucose-induced large amplitude oscillations, there were no Ca(2+)-like pronounced spikes superimposed on an elevated cytoplasmic Ba2+ after elevation of cyclic AMP. Neither could Ba2+ substitute for Ca2+ in being incorporated in response to glucose into a pool mobilizable by carbachol. The studies indicate that cations other than Ca2+ can oscillate in response to glucose, and that such oscillations do not require mobilization from internal pools sensitive to inositol 1,4,5-trisphosphate. PMID- 7986083 TI - Characterization of two distinct allyl pyrophosphatase activities from rat liver microsomes. AB - We have identified and characterized two novel allyl pyrophosphatase activities from rat liver microsomes. One specifically hydrolyzes farnesyl pyrophosphate (FPP) to farnesol and the other converts geranylgeranyl pyrophosphate (GGPP) to geranylgeranol. Hence, we named them farnesyl pyrophosphatase (FPPase) and geranylgeranyl pyrophosphatase (GGPPase) activities, respectively. Other allyl pyrophosphates, i.e., isopentenyl pyrophosphate, dimethyl allyl pyrophosphate, and geranyl pyrophosphate, did not act as substrates for these activities. Both activities are metal ion independent and exhibit acidic pH optima (5.5 and 6.0). Microsomal FPPase has a Km for FPP of 7 microM and a specific activity of 6.8 nmol/min/mg protein at pH 5.5. GGPP is a potent noncompetitive inhibitor of FPPase. FPP has no inhibitory effect on GGPPase activity. Microsomal GGPPase has a Km for GGPP of 12 microM and a specific activity of 14 nmol/min/mg protein. The Km of FPPase activity for FPP increases with an increase in pH. The GGPPase activity remains unaffected with an increase in pH. Metal ions Zn2+ and Mn2+ are potent inhibitors of GGPPase activity. Zaragozic acid B is a weak inhibitor of FPPase/GGPPase activities as compared to squalene synthase. GGPPase activity is inhibited with a fourfold higher IC50 (20 microM) as compared to FPPase (5 microM). Hence, the FPPase and GGPPase activities can be differentiated by zaragozic acid B inhibition. Kinetic analysis of inhibition of FPPase by zaragozic acid B further indicates that it is a mixed type noncompetitive inhibitor. PMID- 7986084 TI - The electron transfer reactions of NADPH: cytochrome P450 reductase with nonphysiological oxidants. AB - The steady-state kinetics of oxidation of rat liver NADPH: cytochrome P450 reductase (EC 1.6.2.4) by quinones, aromatic nitrocompounds, ferricyanide, Fe(EDTA)-, and cytochrome c has been studied. The logarithms of bimolecular rate constants of reduction (kcat/Km) of quinones and nitrocompounds increase with the increase in their single-electronreduction potential (E1(7)), reaching a maximum value at E1(7) > -0.15 V. The reactivities of nitroaromatics are about by an order of magnitude lower than the reactivities of quinones. For a series of nitroaromatics including the compounds with previously undetermined E1(7) values, an orthogonality was found between their reactivities toward cytochrome P450 reductase, flavocytochrome b2 (EC 1.1.2.3), and the NADPH: adrenodoxin reductase (EC 1.18.1.2)-adrenodoxin system. This indicates the absence of significant specific interactions during these reactions. The effects of ionic strength on reaction kinetics and the character of inhibition by a product of reaction, NADP+, are in accordance with the reduction of oxidants at the negatively charged site in the surroundings of FMN of P450 reductase. Quinones inactivate oxidized reductase modifying the NADP(H) binding site. The redox cycling of quinones markedly slows the inactivation. The kinetic data presented are consistent with an outer-sphere electron transfer mechanism. The analysis of kinetics of reduction of cytochrome c, ferricyanide, and Fe(EDTA)- using the model of Mauk et al. (A. G. Mauk, R. A. Scott, and H. B. Gray (1980) J. Am. Chem. Soc. 102, 4360 4363) gives calculated distances of FMN from the surface of protein globule, 0.33 0.63 nm. The data from nitroreductase reactions of cytochrome P450 reductase, flavocytochrome b2, and adrenodoxin were used for approximate evaluation of previously unknown E1(7) of nitrocompounds. PMID- 7986085 TI - Site-directed mutagenesis of tryptophan residues to conserved hydrophobic residues inhibits the processing of human KB cell folate receptor. AB - We are interested in identifying the ligand binding site of the human folate receptor (hFR). Previous reports have suggested a role of tryptophan(W) residues in ligand binding. We used site-directed mutagenesis to change the conserved W residues in positions 86, 116, 142, 143, 156, 160, and 193 of the hFR to either leucine(L) or phenylalanine(F) to examine the role of these W residues in hFR function. Although all W to L changes except W86L produced unstable proteins, W to F changes were tolerated. Based on total folate binding and transport studies, Chinese hamster ovary (CHO) cells transfected with W86L, W116F, and W143F expressed high levels of functional hFR, equivalent to cells transfected with wt hFR. CHO cells transfected with W142F, W156F, W160F, and W193F expressed low or undetectable levels of functional hFR although mRNA was present. Of these four mutants, only W142F expressed easily detectable immunoprecipitable protein but it was not fully glycosylated. Since glycosylation may affect the ability of hFR to bind folate, we expressed W142F in Xenopus oocytes which glycosylate the mutant and wild type proteins to the same apparent extent. In oocytes, the stoichiometry of folate binding was identical between the fully processed mutant protein and the wild type hFR. These results indicate that in CHO cells three of the seven W mutations (W86L, W116F, and W143F) function normally, whereas four of the seven W mutations (W142F, W156F, W160F, and W193F) produce unstable or abnormally processed protein.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7986086 TI - Substrate specificity of CDC2 kinase from human HeLa cells as determined with synthetic peptides and molecular modeling. AB - A systematic study was undertaken in order to assess the substrate specificity of cyclin-B/cell division control protein kinase (CDC2) isolated from human HeLa cells, using 13-15 residue peptides with a central histone-like KKSPKK motif as a model. Replacement of the proline residue by any of the other 19 amino acids or D proline drastically reduces or abolishes phosphorylation by CDC2. Changing the basic residues to Ala on either side of the -SP- structure differentially reduces phosphorylation. Molecular modeling and dynamics simulation indicated that the phosphorylation site of the peptide may have to adopt a turn-like conformation that will orientate the charged and hydrophobic residues so as to allow interaction with postulated binding surfaces within the CDC2 active site. It thus appears that, of the 20 coded amino acids, only proline can provide this conformation in short peptides. This is in agreement with the finding that sarcosine can replace proline in this respect (S. Ando et al. Biochem. Biophys. Res. Commun. 195, 837-843, 1993). PMID- 7986088 TI - Characterization of the group B streptococcal hyaluronate lyase. AB - Hyaluronate lyase is one of several proteins secreted by group B streptococci which are believed to contribute to strain virulence. Characterization of the purified enzyme revealed that it degrades hyaluronan by a mechanism different from that of other previously studied hyaluronidases. Instead of randomly cleaving hyaluronan chains leading to a continuous decrease in average chain size, the group B streptococcal enzyme initially yields primarily unsaturated disaccharides. The observation that most of the free reducing ends generated during group B streptococcal hyaluronate lyase digestion are present in the unsaturated disaccharide units supports the conclusion that they are released primarily from the ends of the hyaluronan chains. Furthermore, the experimental evidence is consistent with a mode of action by which the enzyme initially makes a random cut in a hyaluronan chain and then processively moves along the chain releasing disaccharide units. Group B streptococcal hyaluronate lyase also slowly degrades chondroitin sulfate, and its desulfation greatly increases the reaction rate. A preferential cleavage of unsulfated residues is consistent with the observed extensive release of free chondroitin sulfate chains following very limited digestion of aggrecan from bovine nasal cartilage. PMID- 7986087 TI - The effect of pH on the covalent and metabolic control of C4 phosphoenolpyruvate carboxylase from Sorghum leaf. AB - The influence of pH on the in vitro activity and regulatory properties of Sorghum leaf C4 phosphoenolpyruvate carboxylase (PEPC) was investigated with respect to the phosphorylation status of the enzyme. In vitro protein phosphorylation was achieved using the catalytic subunit of a cAMP-dependent protein kinase (PKA) and a recombinant, immunopurified PEPC (0.9 mol of covalent Pi/mol PEPC subunit). Between pH 6.8 and 8, velocity and IC50 for L-malate increased for both the nonphosphorylated and the phosphorylated forms. With respect to the nonphosphorylated PEPC, the phospho-PEPC always gave high values for these kinetic parameters at the pH range investigated, especially between pH 7 and 7.3. The phosphorylation-induced stimulation of PEPC activity was four- to fivefold at pH 7.1 and approximately twofold at pH 7.3. The IC50 for L-malate showed a two- to threefold increase at pH 7.3, but varied less at pH 7.1 upon PEPC phosphorylation. Thus, phosphorylation of PEPC caused a predominant V effect or a mixed (V/IC50) effect at pH 7.1 or 7.3, respectively. This was also observed with the enzyme from desalted crude protein extracts from dark or light-adapted Sorghum leaves and leaf-derived mesophyll protoplasts illuminated in the presence of methylamine, a compound known to increase cytosolic pH (pHc). At pH 7.3, desensitization to L-malate of phospho-PEPC was due to an enhanced ability of PEP to compete with the inhibitor. The positive effector glucose-6P acted similarly to phosphorylation; however, a combination of both factors (glucose-6P and phosphorylation) led to a much larger increase in the IC50 for L-malate than that observed by a single factor.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7986089 TI - Fractionation of liver microsomes with polyethylene glycol and purification of NADH-cytochrome b5 oxidoreductase and cytochrome b5. AB - A simplified, rapid procedure for the purification of NADH-cytochrome b5 oxidoreductase and cytochrome b5 from either rat or rabbit liver is described. Microsomes were prepared by fractionation with polyethylene glycol and solubilized with Triton X-100. Cytochrome b5 was purified by a two-column procedure, anion exchange chromatography using DEAE-cellulose, and hydrophobic chromatography on phenyl-Sepharose. The final preparation of cytochrome b5 was purified more than a 120-fold from rat or rabbit liver microsomes, with specific content of about 50 nmol per mg protein, and overall yield of 22 to 32%. Only a single band with mol wt of 18,600 was found on sodium dodecyl sulfate (SDS)-gels or on Western blots using a polyclonal antibody raised against the purified b5. NADH-cytochrome b5 oxidoreductase was purified by a three-column procedure, DEAE cellulose, hydroxylapatite, and ADP-agarose. The final product was purified more than 400-fold from rat or rabbit liver microsomes with a yield of about 25% and final specific activity of about 1600 mumol ferricyanide reduced per minute per milligram of protein. A single band with mol wt of 33, 100 was found on SDS-gels. The reductase catalyzed reduction of ferricyanide, dichlorophenol-indophenol, and cytochrome b5. Cytochrome c was reduced in the presence of reductase plus cytochrome b5, and this was inhibited by the anti-b5 IgG. The reductase catalyzed a rapid rate of reduction of ferric-ATP, which was slightly elevated by cytochrome b5. Ferric-histidine and ferric-ammonium sulfate were slowly reduced by reductase; addition of cytochrome b5 markedly stimulated reduction of these ferric complexes but inhibited reduction of ferric-EDTA.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7986090 TI - Cloning and expression of rabbit and human brain tryptophan hydroxylase cDNA in Escherichia coli. AB - Rabbit and human brain tryptophan hydroxylase were cloned and expressed in Escherichia coli. Each of the respective cDNAs, including the complete coding sequence of tryptophan hydroxylase, was obtained by reverse transcription of rabbit or human brain mRNA and subcloned into the expression vector pET-3C. The expressed rabbit brain tryptophan hydroxylase activity, measured in the presence of tetrahydrobiopterin, represents approximately a 50-fold enhancement in yield (units/g tissue (wet wt) over that of a rabbit brain extract. Likewise, the level of expressed human brain tryptophan hydroxylase is approximately 57 times the average yield previously reported for a human brain homogenate and approximately 10-times the activity of homogenates of human raphe nucleus. The rabbit brain and pineal-derived tryptophan hydroxylase sequences varied by disparities in six amino acid residues (99% identity). The human carcinoid and brain peptide sequences varied by disparities in 18 amino acid residues (96% identity). Several properties of both expressed enzymes were studied and compared with those of native tryptophan hydroxylases. PMID- 7986092 TI - Derivatization and purification of bisecting tyrosinamide-oligosaccharides from ovotransferrin. AB - The major N-linked oligosaccharides from ovotransferrin were purified on a large scale. The oligosaccharides were released from 5 g of the glycoprotein using N glycosidase F and isolated from a mixed bed ion exchange column. Reducing oligosaccharides were reacted with ammonium bicarbonate to form a reducing-end glycosylamine which coupled with the N-hydroxysuccinimidyl ester of Boc-tyrosine, resulting in tyrosinamide-oligosaccharides. Resolution of tyrosinamide oligosaccharides on reverse-phase (RP)-HPLC necessitated the removal of Boc by treatment with trifloroacetic acid. Two major tyrosinamide-oligosaccharides were isolated from preparative RP-HPLC and were characterized by 500 MHz proton NMR and FAB-MS. These were a biantennary and triantennary oligosaccharide, each possessing a bisecting GlcNAc residue extending from the central core Man residue. Thus, ovotransferrin represents an abundant glycoprotein source from which to prepare multi-micromole quantities of bisecting complex oligosaccharides which may find utility in exploring the ligand specificity of mammalian lectins or may be used as synthons to prepare novel glycoconjugates. PMID- 7986091 TI - Steroid metabolism by rabbit olfactory-specific P450 2G1. AB - Cytochrome P450 2G1 (2G1), which is uniquely expressed in the olfactory mucosa in mammals, may have important physiological functions. In the present study, we have examined the catalytic activity of rabbit 2G1 toward a number of steroid sex hormones, including androstenedione, estradiol, progesterone, testosterone, and 5 alpha-dihydrotestosterone; the purified cytochrome is active toward all of these compounds in a reconstituted enzyme system with turnover numbers of 1.84, 0.34, 1.46, 1.04, and 0.84, respectively, at a substrate concentration of 5 microM. In the presence of cytochrome b5, the turnover numbers are 1.58, 0.66, 1.66, 2.74, and 1.34, respectively. Estradiol is converted to the 2-hydroxy compound (major product) and 4-hydroxy compound (minor product) by 2G1, and progesterone is converted to the 16 alpha-hydroxy derivative as well as the corresponding keto compound as a secondary product. The same products are formed in olfactory microsomal suspensions as major metabolites of progesterone, and the reactions are inhibited strongly by anti-2G1 IgG. In a reconstituted system, 2G1 has an apparent Km of 2.0 microM and a Vmax of 1.8 nmol/min/nmol P450 for the formation of the 16 alpha-hydroxyprogesterone. Of particular interest, 2G1-catalyzed progesterone metabolism is effectively inhibited by the boar pheromones, 5 alpha androst-16-en-3-one and 5 alpha-androst-16-en-3 alpha-ol, and to a lesser extent by a variety of odorant compounds as well as by known P450 inhibitors, including ketoconazole and alpha-naphthoflavone. The broad substrate specificity and relatively high catalytic efficiency of 2G1 in sex steroid metabolism suggest a role for this unique P450 isozyme in the maintenance of steroid hormone homeostasis in the olfactory mucosa. PMID- 7986093 TI - Effect of tubulin on the activity of the muscle isoenzyme of lactate dehydrogenase. AB - The interaction between muscle-type lactate dehydrogenase (LDHm) and tubulin was investigated by monitoring the combined effect of NADH and tubulin on steady state kinetics and the combined effect of NADH and pH on complex formation between tubulin and the enzyme. Steady-state kinetics showed that LDHm is inhibited by tubulin. Experiments with heart-type lactate dehydrogenase (LDHh) showed that the inhibition is unique to the muscle-type enzyme. The magnitude of the inhibition is dependent upon the concentration of NADH as well as the pH of the buffer medium. The enzyme was less sensitive to inhibition at 50 microM NADH than at 10 microM NADH. Since this effect of NADH is not due to an ionic strength contribution, it is deemed to be specific. In contrast to the absence of tubulin, its presence induced a modification of the kinetic behavior of LDHm; i.e., the velocity dependence on NADH concentration displayed a marked sigmoid response. The inhibition of LDHm by tubulin is more pronounced at lower pH values than at higher pH values. The pH-dependent inhibitory profile is shifted to the left (i.e., pKa is decreased) with increasing concentrations of NADH. This pattern is remarkably similar to that observed for the binding of the enzyme on Sepharose immobilized tubulin and is consistent with the premise that inhibition is a result of interaction between these proteins. NAD+ was much less effective than NADH in dissociating LDHm from immobilized tubulin. Results from these in vitro studies are consistent with similar observations dealing with other glycolytic enzymes and cytoskeleton proteins, which show that enzyme catalytic properties are modified upon binding. PMID- 7986094 TI - Comparison of the effects of cholesterol and oxysterols on phospholipid bilayer microheterogeneity: a study of fluorescence lifetime distributions. AB - The homogenizing effect of cholesterol and its oxidative derivatives, 7 ketocholesterol, cholesterol 5 alpha, 6 alpha-epoxide and 25-hydroxycholesterol, in liquid-crystalline 1,2-dioleoyl-sn-glycero-3-phosphocholine(DOPC) bilayer vesicles was studied using the fluorescence lifetimes of 2-(3 (diphenylhexatrienyl)propanoyl)-1-hexadecanoyl-sn-glycero-3-p hosphocholine (DPH PC). The phase and modulation data were fitted either to discrete exponential models or to models characterized by continuous distributional lifetimes. Among all the models tested, it was found that the best one to account for the experimental data was the unimodal Lorentzian distribution. Thus, the DPH-PC lifetime was adequately described by a distributional center and a full width at half-maximum, for DOPC vesicles these values being 6.23 and 0.48 ns, respectively. Increasing the concentration of cholesterol, 7-ketocholesterol, or cholesterol 5 alpha, 6 alpha-epoxide from 0 to 30 mol% resulted in an increase of the lifetime center (e.g., 7.16 ns at 30 mol% cholesterol) and a decrease of the distributional width (e.g., 0.05 ns at 30 mol% cholesterol). On the other hand, up to 30 mol% of 25-hydroxycholesterol incorporated into the bilayer vesicles showed little influence on both lifetime parameters. Our results support the use of lifetime distributional width to evaluate membrane heterogeneity and suggest that oxysterols, depending on their molecular structural particulars, may exert cholesterol-like homogenizing effect in membranes. PMID- 7986095 TI - Hydrogen peroxide metabolism in skeletal muscle mitochondria. AB - The presence of catalase in heart mitochondria may prevent excessive H2O2 from reaching the cytosol, eventually reacting with myoglobin (R. Radi et al., 1991, J. Biol. Chem. 266, 22028-22034). In this report we investigated whether catalase was also present in the mitochondrial matrix of skeletal muscle as it also contains myoglobin which could react with H2O2 produced by mitochondria. Catalase content of skeletal muscle tissue was about 1.4% of that in liver. Simultaneous determinations of citrate synthase (a mitochondrial marker) and catalase in intact mitochondria and mitoplasts indicated that catalase is not associated with muscle mitochondria. The lack of catalase in muscle mitochondria is not due to a limited H2O2 production by these organelles. Rat skeletal muscle mitochondria generated H2O2 (0.64 +/- 0.04 nmol/(min.mg protein), approximately 40% the rate in heart mitochondria. Other groups have shown that training causes an increase in the concentration of mitochondrial electron carriers as well as an increase in the activity of mitochondrial glutathione peroxidase and mitochondrial electron carriers. The increased concentration of mitochondrial electron carriers and the sudden changes in oxygen supply may lead to increased intracellular H2O2 during exercise. PMID- 7986096 TI - Purification and characterization of the bcl-2 protein. AB - The oncogene product bcl-2 functions as a repressor of programmed cell death and is a 26-kDa protein with a single predicted transmembrane segment located at the carboxyl terminus. The bcl-2 protein seems to function in different subcellular compartments, as evidenced by several biochemical and ultrastructural studies. The present study was performed to purify bcl-2 protein in significant quantities necessary for structural and functional studies. For this purpose, the bcl-2 gene was over-expressed in either baculovirus system or lymphocytes. Initially, attempts were undertaken to purify bcl-2 protein using conventional methods such as ion exchange or gel filtration chromatography. During these purification attempts we determined that bcl-2 protein is highly hydrophobic and prone to aggregation as might be expected for an integral membrane protein. By ion exchange and gel filtration chromatography, this protein could be partially purified. In order to purify bcl-2 to apparent homogeneity and avoid the aggregation problem, we prepared immunoaffinity columns using a monoclonal antibody developed against a synthetic peptide chosen from residues 61-76 of the amino acid sequence of human bcl-2. The antibody was either coupled to CNBr activated Sepharose 4B or cross-linked into protein A-Sepharose by dimethylpimelimidate dihydrochloride. Cellular extract equivalent to 10(8) bcl-2 overexpressing insect cells or lymphocytes was applied to immunoaffinity columns. Approximately 500 micrograms purified bcl-2 protein could be recovered as estimated by silver staining and immunoblotting. Furthermore, purified bcl-2 protein was electroporated into Pre-B lymphocytes which do not express this protein in sufficient quantity to delay the onset of glucocorticoid-induced apoptosis.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7986097 TI - Baculovirus expression of bovine cytochrome P450c17 in Sf9 cells and comparison with expression in yeast, mammalian cells, and E. coli. AB - Expression of bovine 17 alpha-hydroxylase cytochrome P450 (P450c17) in insect Sf9 cells using baculovirus is the fourth heterologous expression system developed for studying this enzyme. The enzyme in Sf9 cell membranes has all the expected activities and closely resembles that from the other systems: COS1 cells, yeast, and Escherichia coli. One curious feature of baculovirus expression of this hemoprotein is that the immunodetectable P450c17 is present in an insoluble pellet when produced in the absence of added hemin and in a 10,000 g supernatant when expressed in the presence of added hemin. When comparing the level of expression of bovine P450c17 in these different expression systems, E. coli produces the largest quantity per liter culture, while baculovirus produces the most molecules of P450c17 per cell. PMID- 7986098 TI - Purification and characterization of two rat liver microsomal carboxylesterases (hydrolase A and B). AB - The enzymatic hydrolysis of para-nitrophenylacetate by rat liver microsomes is predominantly catalyzed by two esterases: one with high affinity (Km approximately 25 microM) and one with low affinity (Km approximately 400 microM) for the substrate. Two kinetically distinct esterases were similarly detected in liver microsomes from mouse, hamster, guinea pig, rabbit, cat, cynomolgus monkey, and human, but only the high-affinity enzyme was detectable in dog liver microsomes. The tissue distribution of these kinetically distinct esterases was examined in rats. High-affinity (Km 20-35 microM esterase activity toward para nitrophenylacetate was detected in testis, lung, prostate, and pancreas. The activity in testicular microsomes was comparable to that in liver microsomes. Low affinity (Km 200-700 microM) esterase activity was detected in kidney, small intestine, lung, spleen, heart, and brain. The activity in kidney microsomes was comparable to that in liver microsomes. The high-affinity esterase in testicular and liver microsomes was highly sensitive to the inhibitory effects of phenylmethylsulfonyl fluoride (PMSF), whereas the low-affinity esterase in kidney and liver microsomes was relatively resistant. These results suggested that rat liver microsomes contain two esterases with high activity toward para nitrophenylacetate, a PMSF-sensitive esterase with high substrate affinity, and a PMSF-insensitive esterase with low substrate affinity. In support of the hypothesis, we have purified and characterized two esterases, designated hydrolases A and B, which appear be the only abundant enzymes in rat liver microsome that rapidly hydrolyze para-nitrophenylacetate. Hydrolase A hydrolyzed para-nitrophenylacetate with high affinity (Km approximately 25 microM), and was inhibited by extremely low concentrations of PMSF (IC50 approximately 100 nM). In contrast, hydrolase B hydrolyzed para-nitrophenylacetate with low affinity (Km approximately 400 microM) and was inhibited only by relatively high concentrations of PMSF (IC50 approximately 100 microM Paraoxon, the active metabolite of parathion, and cresylbenzodioxaphosphorin oxide, the active metabolite tri-ortho-tolylphosphate, completely inhibited the hydrolysis of pra nitrophenylacetate by rat liver microsomes and by hydrolases A and B, whereas the sulfhydryl agent, para-chloromercurobenzoate, was not inhibition. These results suggest that hydrolases A and B are both serine esterases. The N-terminal amino acid sequence of hydrolases A and B were similar but distinct (23 the first 30 amino acid residues were identical), indicating that these two esterases are isozymes.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 7986099 TI - Regulation of two rat liver microsomal carboxylesterase isozymes: species differences, tissue distribution, and the effects of age, sex, and xenobiotic treatment of rats. AB - The preceding paper described the purification of two rat liver microsomal carboxylesterases, designated hydrolases A and B, that have high affinity (Km approximately 25 microM) and low affinity (Km approximately 400 microM) for para nitrophenylacetate, respectively. The present study describes the preparation and purification of polyclonal antibodies against these purified enzymes. Each antibody was subjected to immunoabsorption chromatography to remove antibodies against epitopes common to both hydrolases A and B. The resulting isozyme specific antibodies were used to study the regulation of hydrolases A and B by Western immunoblotting and Ouchterlony immunodiffusion. Liver microsomes from mouse, hamster, rabbit, guinea pig, cat, dog, cynomolgus monkey, and humans contained one or more proteins that were immunochemically related and similar in size (M(r) approximately 60 kDa) to hydrolase A and/or hydrolase B. These proteins were preferentially recognized by the antibody against hydrolase A, except for cat liver microsomal esterase, which was preferentially recognized by antibody against hydrolase B. In rats, the levels of hydrolases A and B in liver microsomes were coregulated as a function of age, sex, and xenobiotic treatment of rats. The levels of both enzymes were very low in 1- and 2-week-old rats, but increased abruptly at 3 weeks of age in both male and female rats. Treatment of mature male rats with 11 known microsomal enzyme inducers caused little (< 35%) or no induction of hydrolase A or B, whereas treatment of rats with beta naphthoflavone, pregnenolone- 16 alpha-carbonitrile or dexamethasone suppressed the levels of both enzymes. The kinetic analysis of para-nitrophenylacetate hydrolysis described in the preceding paper identified a high-affinity esterase (Km 20-35 microM) in rat liver, testis, lung, prostate, and pancreas and identified a low-affinity enzyme (Km 300-800 microM) in liver, kidney, small intestine, lung, brain, spleen, and heart. Immunoblot analysis established that hydrolase A was present in liver, testis, lung, and prostrate at concentrations that accounted for the high-affinity esterase activity in these tissues. Hydrolase A was not detected in the pancreas, even though this tissue contained low levels of a high-affinity esterase. Hydrolase B was detected in liver and kidney at concentrations that accounted for the low-affinity esterase activity in these tissues. Hydrolase B was not detected in the other tissues examined, some of which (e.g., small intestine) contained high levels of a low-affinity esterase. These results indicate that hydrolases A and B are independently expressed in a wide variety of extrahepatic tissues in rats.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 7986100 TI - Expression of a plant sesquiterpene cyclase gene in Escherichia coli. AB - 5-Epi-aristolochene synthase is a sesquiterpene cyclase activity found in pathogen-challenged tobacco cells, but not in nonchallenged tissues, and appears to be encoded by a complex gene family. As a prerequisite to assessing the functional significance of these multiple genes, bacterial expression systems were examined for their capacity to express a tobacco sesquiterpene cyclase cDNA. Insertion of full-length 5-epi-aristolochene synthase cDNA into two commonly used expression vectors, pET-11d and pGBT-T19, resulted in high level expression of the cyclase activity. The highest level of expression occurred 3 h after induction with low concentrations (0.1-0.5 mM) of IPTG, incubation at 27 degrees C instead of 37 degrees C, and in the bacterial host strain BL21(DE3). Under these conditions, the cyclase protein constituted 5 to 8% of the soluble and 35% of the total Escherichia coli proteins. Enzyme reaction products of the native tobacco and recombinant enzyme were identical, based on argentation-thin layer chromatography. Deletion mutants of the cyclase gene corresponding to the amino and carboxy termini of the enzyme were prepared. The cyclase proteins resulting from bacterial expression of these mutant constructs were found largely in the insoluble protein fraction and no soluble enzyme activity was detected. PMID- 7986101 TI - Comparison of thermodynamic and kinetic effects between the Leu32-->norvaline and Leu35-->norvaline substitutions of the three-fragment complex of cytochrome c. AB - The three fragment complex (1-25)H.(28-38).(39-104) of horse cytochrome c (e.g., (1-25)H, the heme fragment containing residues 1 to 25) closely resembles the native protein except for residues 39 to 55, which are flexible. We have investigated how the Leu35-->Nva (norvaline) substitution differs from the Leu32- >Nva in the perturbation of the stability of this complex. The side chains of Leu32 and Leu35 are adjacent in the well-packed hydrophobic core of tuna cytochrome c (T. Takano and R. E. Dickerson (1981) J. Mol. Biol. 153, 95-115). We measured the effects of the substitutions on (i) the binding of (28-38) with ferri- and ferrocomplexes on the right side of the heme (Dickerson's orientation); (ii) the heat stability of the 695-nm band which monitors the Fe-S bond on the left side of the heme (cf. Takano and Dickerson, 1981); and (iii) the rate constant for the direct dissociation of (39-104) of the ferrous complex as a function of temperature. The results suggest that the Leu32-->Nva is unique in that the stabilizing energy associated with the ground state is markedly more perturbed in the Leu32-->Nva than in the Leu35-->Nva. This is true despite the fact that both substitutions introduce no stereochemical conflict and remove only the gamma-methyl groups of the Leu side chains which are presumably positioned adjacently with respect to each other in the core. Furthermore, the effect of the perturbation of the structure imposed by the removal of the Leu32 gamma-methyl group propagates itself perhaps through the core and affects the stability of the Fe-S bond and the binding strength of (39-104). These properties resemble the core domain-domain interaction (A. Fisher and H. Taniuchi (1992) Arch. Biochem. Biophys. 296, 1-16). PMID- 7986102 TI - The reconstituted mitochondrial adenine nucleotide translocator: effects of lipid polymorphism. AB - This study investigates the role of polymorphic or nonbilayer lipids in the function of an integral membrane protein which is a key component of the mitochondrial energy transduction apparatus. The adenine nucleotide translocator (AdNT) has been isolated from rat heart mitochondria and reconstituted into ATP containing liposomes composed of dioleoylphosphatidylcholine (DOPC), dioleoylphosphatidylethanolamine (DOPE), and cardiolipin (CL). CL content was held constant at 11.1 mol%; the ratio of DOPC:DOPE was varied to manipulate R0, the intrinsic radius of curvature of the bilayer [S. M. Gruner (1985) Proc. Natl. Acad. Sci. USA 82, 3665-3669]. Translocator activity was determined fluorometrically, using a coupled enzyme system to measure ADP-induced efflux of ATP. Specific activity was calculated based on the number of functional translocators in each preparation, quantified using the tight-binding inhibitor carboxyatractylate (CAT). AdNT specific activity was a smooth function of R0, with a maximum at a lipid composition similar to that of the inner mitochondrial membrane. Protein incorporation was constant at DOPC:DOPE ratios > 1, but appeared to increase at ratios < or = 1. The fraction of reconstituted AdNT incorporated in the native mitochondrial orientation, estimated from inhibition by 10 microM CAT, was independent of lipid composition and > 85%. Leakage of encapsulated ATP increased at low R0 values both in the presence and absence of protein. PMID- 7986104 TI - [The present status and prospects for clinical oncology in Japan]. AB - The present status and prospects for clinical oncology in Japan were reported. Clinical oncology in Japan is still developing, although some research has attained the international level. This is because there are some problems in ethics of clinical trials, education of medical oncologists in medical schools, systems of cancer-related associations and the research system of clinical trials for cancer treatment. The education of medical oncologists and improvement of the research system in clinical oncology are required in order to develop clinical oncology in Japan. PMID- 7986103 TI - Hormonal modulation of peroxisomal enzyme induction caused by peroxisome proliferators: suppression by growth and thyroid hormones in cultured rat hepatocytes. PMID- 7986105 TI - [The introduction of new drugs from the basic research to clinical application- issues in the drug development]. PMID- 7986106 TI - [Recent proposals for early stage clinical trials of cancer]. AB - Statistical designs for early stage cancer clinical trials, which include continual reassessment method for phase I and I-II studies, early stopping of phase II studies, randomized phase II and multi-stage phase II studies, are shortly reviewed. These recent proposals should be examined further as regards to their statistical characteristics as well as their ethical implication. PMID- 7986107 TI - [Current status and issues in clinical trials of anticancer agents]. AB - NDA filing and government approval for drug manufacturing marketing rights are processes based on collaboration among the concerned parties; a drug manufacturer (or importer), a medical institution and a government agency. However, quality guidelines are necessary for a scientific, ethical and economically efficient clinical study to be conducted. It is more than 3 years since the Ministry of Health and Welfare of Japan introduced "The Guidelines on Clinical Evaluation for Anti-tumor Drugs" in February, 1991. However, some practical problems have been pointed out by clinicians for revision. Among them we discuss the following items for revision of the Guidelines and made suggestions and opinions from the manufacturers' point of view: Phase I: Number of institutions for clinical study, determination of MTD and study design. Phase II: Introduction of foreign data, late phase II study for plural numbers of indications at time of NDA filing and evidence of usefulness in concurrent therapy. PMID- 7986108 TI - [Preclinical studies for development of anti-cancer drugs: current and historical status and problems]. AB - In this review, we present the current and historical status of preclinical studies for development of new anti-cancer drugs. In our company, especially focusing on the stage of drug screening, pharmacology, toxicology and pharmacokinetic studies. We have discovered numerous new compounds with anti cancer potential mainly with microbial origins, from which some drugs have been developed to clinical trials. We hope that clinical trials of drugs with a new mode of action will be designed and conducted with a more rational basis, and followed by analysis of the pharmacokinetics and pharmacodynamics so as to predict the toxicity and efficacy of the drugs in humans. PMID- 7986109 TI - [Clinical pharmacology in development of new anticancer agents]. AB - The role of clinical pharmacology in the development of new anticancer agents is discussed. In phase I studies, analysis of pharmacokinetic (PK) and pharmacodynamic (PD) relationship, in other words, the relationship among dose administered, pharmacological parameters and pharmacodynamic effects, is essential in the dose escalating process. In addition, we must pay careful attention to whether linearity between the dose administered and the pharmacological parameters is observed or not so as to assure a safe dose escalation strategy. Comparative analysis of the pharmacokinetics and pharmacodynamics between animal models and patients are also an important factor in safe dose escalation. A simple dose escalation strategy will be possible in such agents as the results of phase I are available in other countries. The concept of pharmacokinetic and/or pharmacodynamic drug interactions is essential in a combination phase I study, although this is not covered in the Good Clinical Practice (GCP) guideline. Pharmacological analysis should continue phase II studies to obtain a more accurate PK/PD relationship not only as to the side effects but also the clinical response, in order to analyze intra- or inter patient variability in pharmacokinetics as well as pharmacodynamics. This would also be useful to establish population pharmacokinetic model or limited sampling strategy for phase III evaluation. PMID- 7986110 TI - [Present strategy for new drug development in the USA]. AB - Development of new anticancer drugs is essential to improve the response and survival of cancer patients. Nationally supported organizations have a key role in conducting very experimental expensive and ethical clinical trials. In the U.S., the NCI-US has designated six cancer centers as "phase I institutes for new drug evaluation," supported by NCI funding. CTRC and JHOC are active centers for phase I trials. They have evaluated more than 10 new drugs a year. Their team consists of younger physicians, research nurses, data managers, pharmacologists, technicians and the primary investigator under strong leadership. Recently, international harmonization of the U. S., -Europe and Japan is postulated politically, However, we have to recognize that this interrelationship has another meaning, that of "international competition and comparison" with each other in the field of new drug development. PMID- 7986111 TI - [Clinical trials of new antitumor drugs in hematopoietic malignancies]. AB - Although there is general agreement regarding the overall research goals of clinical trials of new antitumor drugs, there is a difference between the goal for chemotherapy sensitive tumors such as hematopoietic malignancies or germ cell tumors and the insensitive tumors such as most solid tumors. Hematopoietic malignancies like leukemia or malignant lymphoma are highly responsive to chemotherapy, approximately 70% of patients can reach complete remission, and some can survive for a long time. Furthermore, hematopoietic malignancies have a low incidence and the disease progresses rapidly. In this situation, clinical trials of new drugs for hematopoietic malignancies should be designed in the most efficient and ethically appropriate way. In this paper, we reviewed the recent clinical trials of new drugs for acute leukemia or malignant lymphoma. On the basis of these reviews, we proposed a frame-work that may improve the protocol design and address the ethical issues of phase studies for the development of new drugs for hematopoietic malignancies. PMID- 7986112 TI - [Principles for adjuvant and neoadjuvant chemotherapy]. AB - Early systemic therapy, either immediately after treatment of the primary tumor with surgery (adjuvant chemotherapy) or as initial treatment before local control (neoadjuvant chemotherapy) has been carried out to attempt to eliminate occult micrometastatic disease. The principal goal of adjuvant/neoadjuvant treatment is to increase the effectiveness of treatment over what can be obtained from surgery alone. The primary endpoint of interest is survival. Disease- or recurrence-free survival is often used as a surrogate measure of survival. Adjuvant/neoadjuvant chemotherapy studies generally employ regimens that have appeared most active against the same tumor in advanced stages. The doses and schedules used in the adjuvant setting have also paralleled those for advanced disease. Recently, a prospective randomized study of adjuvant chemotherapy in the patients with breast cancer have shown that the increase of dose intensity of chemotherapy lead to improved disease-free and overall survival. Moreover, prospective randomized studies are needed to support timing decisions for adjuvant/neoadjuvant chemotherapy. While awaiting the appearance of more effective drugs and more sensitive staging techniques, we should continue to investigate variations of dose and schedule of adjuvant/neoadjuvant chemotherapy. PMID- 7986113 TI - [Current status of clinical trials on pre- and postoperative chemotherapy for head and neck cancer]. AB - The purpose of this paper is to discuss the current status and issues of clinical trials in pre- and post-operative chemotherapy for head and neck cancer, focusing on 1) neo-adjuvant chemotherapy, 2) concurrent radiotherapy and chemotherapy, and 3) adjuvant chemotherapy. Although neo-adjuvant chemotherapy did not increase survival, it produced a higher rate of organ preservation in some sites such as the larynx and maxilla. Concurrent radiotherapy and chemotherapy is the most promising primary chemotherapy approach to prolong survival of patients with locally advanced resectable and unresectable disease. It is the only systemic approach consistently shown to improve local-regional control and survival in randomized trials. No survival benefit is evident in trials of adjuvant chemotherapy, the third major treatment category, but some randomized trials produced a significant reduction in distant relapse rate. Based on the results obtained so far, future clinical trials should be continued to search for more effective programs in the systemic control of advanced head and neck cancer. PMID- 7986114 TI - [Problems and present status of clinical trials for esophageal carcinoma]. AB - This paper reviews clinical trials for esophageal carcinoma, mainly from the results of the JEOG (Japanese Esophageal Oncology Group) study. Preoperative radiotherapy was not conducive to survival of esophageal cancer patients. On the third JEOG trial, postoperative chemotherapy of CDDP+VDS was equivalent to survival as 50Gy of postoperative irradiation. And on the further fourth trial, survival was also equivalent between the two groups treated with surgery alone or postoperative chemotherapy of CDDP+VDS. This fact reveals the in effectiveness of these therapies. The response rate from JEOG phase II study of CDDP and 5-FU was 35.9%, and RCT of surgery alone versus surgery + postoperative chemotherapy with CDDP+5-FU was ongoing as the fifth JEOG trial. Chemo-radiotherapy seemed to be very effective for esophageal cancer patients, and it may provide a complete cure for them in the future. PMID- 7986115 TI - [Adjuvant chemotherapy for non-small cell lung cancer. WJSG: West Japan Study Group for Lung Cancer Surgery]. AB - Surgery is the treatment of choice for non-small cell lung cancer (NSCLC). But even for potentially curative resection, patients often die of relapse, and five year survival rates are about 70 percent even for stage I patients. Hence, considering the necessity of post-operative adjuvant chemotherapy, many comparative trials have been undertaken internationally as well. It is important to undertake randomized comparative trials with the survival endpoint, comparing with surgery alone, and to assess the efficacy of adjuvant chemotherapy. Cisplatin-based regimens, which are effective for anti-tumor results as a surrogate endpoint, are used routinely in adjuvant settings. However, the reliability of these adjuvant trials is not yet verified at present. This paper reports on the adjuvant chemotherapy results for NSCLC patients who had undergone a completely curative resection, considering QOL (Quality of Life) and immunity. PMID- 7986116 TI - [Neoadjuvant and adjuvant chemotherapy of bladder cancer]. AB - Conventional treatments such as surgery and radiotherapy for deeply invasive, clinically non-metastatic bladder cancer are associated with cure in less than 30% of cases. This has led to the search for new approaches to therapy. Based on the excellent results with combination chemotherapy such as M-VAC in patients with advanced disease, neoadjuvant or adjuvant chemotherapy has been advocated to improve survival. Twenty patients with primary invasive bladder cancer who underwent radical cystectomy received postoperative adjuvant chemotherapy using a CAP (cyclophosphamide, doxorubicin and cisplatin) or modified M-VAC (methotrexate, vinblastine, pirarubicin and cisplatin) regimen. Sixteen of the patients were treated with CAP and four with the modified M-VAC. Of the 20 patients, 17 had transitional cell carcinoma with or without non-transitional cell elements. All of the patients had tumors with a histological grade of G2 (six cases) or G3 (14 cases). As for lymph node metastasis, there were 10 N0 cases, three N1 cases, six N2 cases, and one N3 case. The five-year survival rate of these 20 patients was 65.9%, while that of 49 patients not administered any adjuvant chemotherapy was 29.9%. Regarding toxicity, both adjuvant chemotherapy regimens in this study were generally well tolerated. The most common toxic effects were gastrointestinal symptoms, alopecia and myelosuppression. Twenty other patients with invasive transitional cell carcinoma of the bladder received two or three cycles of neoadjuvant chemotherapy using the modified M-VAC or MEC (methotrexate, epirubicin and cisplatin) regimen prior to radical cystectomy or partial cystectomy. Of 19 evaluable patients who received neoadjuvant chemotherapy, a complete response was observed in two (10%), a partial response in 11 (55%), and no change in six (30%). The overall response rate was 65%. The five-year survival rate of 20 patients who received neoadjuvant chemotherapy was 74.2%. Regarding toxicity, one patient died of a bowel complication after surgery, and the complication was suggested to be drug-induced. PMID- 7986117 TI - ["State of the art" of adjuvant chemo-endocrine therapy for breast cancer in Japan]. AB - Breast cancer is a solid tumor moderately responsive to chemotherapy and/or endocrine therapy. Based upon meta-analysis covering 233 prospective randomized clinical trials, a consensus about adjuvant chemo and endocrine therapy has been reached according to prognostic factors, including nodal status, tumor size, estrogen receptor and histological grade. The preventive effect of tamoxifen against recurrence has been also proven in Japanese ACETBC (adjuvant chemoendocrine therapy for breast cancer) trials and KEIO BR1 trial. Several other prospective randomized trials have been run in Japan, and the results will be obtained within several years. The features of breast cancer in Japan are low incidence and good prognosis. In these circumstances, the accrual of a vast number of patients and multi-institutional collaboration are essential. The issues under investigation include best chemotherapy dosage and duration, identification of risk factors and the role of preoperative chemotherapy. PMID- 7986118 TI - [Chemotherapy of brain tumors]. AB - Despite recent attempts to improve chemotherapeutic approaches for the treatment of malignant gliomas, results remain limited and palliative. The development of effective chemotherapy for tumors of the central nervous system (CNS) is complicated in that the blood-brain barrier (B.B.B.) hampers the penetration of most drugs into the brain and cerebrospinal fluid. The factors governing delivery in the brain are the drug's molecular weight, lipophilicity and degree of ionization. Now the standard therapy for malignant glioma is maximal tumor resection followed by combination radiotherapy plus chemotherapy. Nitrosoureas are representative drugs which easily cross the B.B.B.. It has been shown that nitrosourea compounds have an additive effect to radiotherapy. The toxicity profile of nitrosoureas is leukocytopenia and thrombocytopenia as a dose-limiting factor. Furthermore, the great heterogeneity of malignant glioma tissues offered a rationale for the use of multiple drugs. Many studies were reported to show a substantial advantage for the multidrug regimen over control series utilizing single drugs alone. Despite clear examples of the effectiveness of chemotherapy, we are still far from improving the cure rate for the vast majority of patients with primary malignancies of the CNS. Further improvement in patient survival may depend upon understanding and manipulating the pathways that regulate aberrant growth in these tumors. The development of new anticancer agents, which are sensitive to malignant glioma and can reach a high concentration in glioma tissue, is warranted. PMID- 7986119 TI - [Overview of clinical trials on adjuvant chemotherapy for curatively resected gastric cancer]. AB - Reports of the results of clinical trials on adjuvant chemotherapy for curatively resected gastric cancer were reviewed. All but two trials did not show its efficacy. In spite of this, understanding some results of subset analysis as definite proof, a consensus was achieved in Japan on its efficacy due to lack of proper knowledge of medical statistics among surgeons. Recently it has been recognized that this consensus was groundless and that evaluation of adjuvant chemotherapy should be carried out again. The results of the trial of JCOG, comparing adjuvant chemotherapy versus control (surgery alone) are therefore awaited. For the moment, all clinical trials on adjuvant chemotherapy for curatively resected gastric cancer should have an arm of surgery alone as control. PMID- 7986120 TI - [Clinical trials for gynecological cancers (especially ovarian cancers) in Japan, current situation and problems--focusing on differences in the system of study used by Japanese Study Group and the Gynecologic Oncology Group in the United States]. AB - One of the major problems in treating ovarian cancers at present is how to cure patients with platinum-resistant tumors. Although clinical trials for ovarian cancers in both Japan and the United States have focused on this issue, most Japanese clinical studies in this field have been of poor quality because group studies have not been functioning efficiently. In spite of a tremendous effort, there are several obstacles to overcome before establishing an efficient study group. Keys to perform productive group studies would be as follows: 1) Since most cancer patients in Japan have been treated by physicians whose subspecialty is not oncology, the organization of cancer centers in major local hospitals or the establishment of qualifications for cancer practice is necessary. 2) Because the term "clinical trial" raises the fears of being a "guinea pig" among Japanese, better education of the public, including patients, families, government bodies and even physicians, is necessary to make them understand that only through clinical trials can effective treatment be achieved in the future. 3) Qualification of research nurses and research secretaries is required to save time and make for competent trials. 4) Sufficient government treating is required to keep any commercial bias out of the trials. Finally, 5) strict quality control by the protocol committee of the study groups is mandatory. PMID- 7986121 TI - Clearing of melanoma in situ with intralesional interferon alfa in a patient with xeroderma pigmentosum. PMID- 7986122 TI - Erythroderma. A clinicopathological study of 56 cases. AB - BACKGROUND AND DESIGN: Erythroderma may be the result of many different causes. There are several publications on this subject, most of them from England, the United States, and the Scandinavian countries reporting a different incidence of each etiologic group. Our objective has been to determine the frequency of erythroderma in our environment, its cause, and patient evolution. We reviewed the clinical, laboratory, and biopsy material of 56 patients diagnosed with erythroderma who were treated in our department in the last 8 years (1984 through 1991). Patients were followed up to know the evolution of the erythroderma. RESULTS: The male-female ratio was 4:1. The mean age at diagnosis was 57 years. Dermatoses were the most frequent cause of erythroderma (62.5%), followed by topical or systemic drug reactions (16%), and cutaneous T-cell lymphomas (12.5%). Follow-up information was obtained from 42 patients (66%). Eight patients died (19%), but only in three cases was death directly related to erythroderma (7.14%). The group associated with the best prognosis was that related to drugs. The best clinicohistologic correlation was found in cutaneous T-cell lymphoma related erythroderma. CONCLUSIONS: Erythroderma of unknown cause and protracted course may be secondary to senile atopic dermatitis, intake of drugs overlooked by the patients, and patients who are in slow progression to cutaneous T-cell lymphoma. Close follow-up of erythrodermas of unknown cause by repeating cutaneous biopsies will in time allow an early diagnosis in patients in the latter group. PMID- 7986123 TI - Tattoo removal using the alexandrite laser. AB - BACKGROUND: Until the recent development of the Q-switched lasers, it was not possible to remove tattoos without causing scarring, sometimes very disfiguring. Variations in wavelengths and pulse widths used may result in different clinical effectiveness or risks. The objective of this study was to determine the effectiveness of the alexandrite laser in removing professional and amateur tattoo pigment without adverse tissue response. RESULTS: We describe the clinical and histologic effects of the use of a new Q-switched laser for treatment of tattoos, the alexandrite laser (wavelength, 755 nm; pulse width, 100 nanoseconds). The results of treatment of 17 patients with professional tattoos and eight patients with amateur tattoos are analyzed. Greater than 95% removal of tattoo pigment averaged 8.9 treatment sessions. Transient hypopigmentation occurred in approximately 50% of patients, and transient textural surface changes occurred in 12%. CONCLUSIONS: The alexandrite laser is a safe and effective treatment modality for removal of black and blue-black tattoo pigment. PMID- 7986124 TI - Treatment of epidermal pigmented lesions with the frequency-doubled Q-switched Nd:YAG laser. A controlled, single-impact, dose-response, multicenter trial. AB - BACKGROUND AND DESIGN: The removal of benign, aesthetically important, pigmented lesions can be effectively treated with multiple modalities. Selective removal of the pigment by lasers is becoming increasingly popular. A three-center trial evaluated the effectiveness of the frequency-doubled Q-switched neodymium (Nd):YAG laser (532 nm, 2.0-mm spot size, 10 nanoseconds) in removing benign epidermal pigmented lesions with a single treatment. Forty-nine patients were treated for multiple lentigines (n = 37), for cafe au lait macules (n = 7), and for miscellaneous lesions (n = 5). Treatment areas were divided into four quadrants, irradiated with fluences of 2, 3, 4, or 5 J/cm2 and evaluated at 1- and 3-month intervals following treatment. RESULTS: For lentigines, response was related to dose with a greater than 75% pigment removal achieved in 60% of those lesions treated at higher energy fluences. Responses were more variable with other lesions, with fair-to-good improvement noted in most cases. Mild, transient erythema; hypopigmentation; and hyperpigmentation were noted in several patients, but resolved spontaneously within 3 months. No other textural changes, scarring, or other side effects were noted. CONCLUSION: The frequency-doubled Q-switched Nd: YAG laser (532 nm) safely and effectively treats benign epidermal pigmented lesions. PMID- 7986126 TI - Acute erythroderma as an exclusion criterion for idiopathic CD4+ T lymphocytopenia. AB - BACKGROUND: Idiopathic CD4+ T lymphocytopenia is defined as a CD4+ T lymphocytopenia of less than 0.3 x 10(9)/L that is not associated with human immunodeficiency virus, other immunodeficiency, or immunosuppressive therapy. The associated clinical course and laboratory findings are variable. We describe a subset of patients whose peripheral CD4+ T-lymphocytopenia was transient, and suggest a pathomechanism for this phenomenon. OBSERVATIONS: We describe three patients with cutaneous T-cell lymphoma, atopic dermatitis, or psoriasis in whom acute erythroderma was concomitant with a peripheral CD4+ T lymphocytopenia that normalized after resolution of the erythroderma. Immunoperoxidase staining of skin biopsy specimens and quantitative estimation of CD4+ T lymphocytes in the cutaneous and peripheral blood compartments demonstrated that the peripheral CD4+ T lymphocytopenia in these cases most probably resulted from sequestration of CD4+ T lymphocytes in the skin. The skin of an erythrodermic patient appears capable of sequestering 10(10) to 10(11) CD4+ T lymphocytes, whereas the peripheral blood compartment contains in the range of 10(9) CD4+ T lymphocytes. CONCLUSIONS: We propose that CD4+ T lymphocytopenia can occur as a result of acute erythroderma of multiple causes and that acute erythroderma associated with transient CD4+ T lymphocytopenia be considered as an exclusion criterion for idiopathic peripheral blood CD4+ T lymphocytopenia. PMID- 7986127 TI - Changes in clinical features, histologic findings, and antigen profiles with development of pemphigus foliaceus from pemphigus vulgaris. AB - BACKGROUND AND DESIGN: Several articles have described patients with pemphigus who showed a transition from pemphigus vulgaris (PV) to pemphigus foliaceus (PF) or vice versa. However, there have been no adequate reports in the literature on the association between transition in disease type and change in autoantibody reactivity against the pemphigus antigens. We investigated the antigen profiles of the serum samples obtained from two patients with pemphigus who were demonstrated to shift from PV to PF with evidence from clinical, histologic, and immunohistologic findings. Western blot technique was performed using normal human epidermal extracts as an antigen source. RESULTS: The serum samples of both cases at the PV stage reacted with the 130-kd antigen and the serum samples at the PF stage reacted with the 150-kd antigen. Accordingly, the dermatologic, histologic, and immunohistologic findings before and after the transition from PV to PF were clearly related to changes in the serum reactivity with the pemphigus antigens. CONCLUSIONS: This was the first investigation completely demonstrating changes in antigen profiles at the molecular level consistent with transition from the PV to the PF form of the disease. Moreover, the findings of this study confirmed the existence of a close correlation between the 130- and the 150-kd antigens, with the onset of each form of the disease. PMID- 7986125 TI - Antiepiligrin cicatricial pemphigoid. A subepithelial bullous disorder. AB - BACKGROUND: Epiligrin is a glycoprotein complex deposited in extracellular matrix by cultured human keratinocytes that serves as the major integrin ligand of these cells. In human skin, epiligrin is found at the interface of the lamina lucida and lamina densa in epidermal basement membrane where it is believed to be associated with anchoring filaments and plays an important role in keratinocyte adhesion. METHODS AND RESULTS: We have identified six patients with a subepithelial bullous disorder of mucous membranes and skin who have IgG anti basement membrane autoantibodies that immunoprecipitate epiligrin from human keratinocyte extracts and culture media. These patients' IgG autoantibodies also bind epiligrin in human keratinocyte extracellular matrix and epidermal basement membrane as determined by immunofluorescence and immunoelectron microscopy. Studies of 10 patients who are clinically indistinguishable from subjects with anti-epiligrin autoantibodies (ie, cicatricial pemphigoid patients) found that while seven had anti-basement membrane autoantibodies, the latter are directed exclusively against a region of epidermal basement membrane that does not contain epiligrin, are present in low titer (ie, < or = 1:10), do not react with keratinocyte extracellular matrix, and do not bind epiligrin (or any other specific antigen) in immunoprecipitation studies of human keratinocyte extracts or media. Antiepiligrin autoantibodies were also not detected in studies of 36 additional patients with bullous diseases or six normal volunteers. CONCLUSIONS: Cicatricial pemphigoid is a disease phenotype in which patients' autoantibodies may target different constituents of epidermal basement membrane. Antiepiligrin autoantibodies are a specific immunologic marker for a group of patients with a disease entity that we propose to designate antiepiligrin cicatricial pemphigoid. PMID- 7986128 TI - Managed care in California. Daunting new realities for dermatology and academic medicine. AB - Managed care is the predominant method of health care delivery in Sacramento, Calif; the effect on our academic medical center is profound. The lessons we are learning in the development of a university-based health care network have applicability to dermatology. The future of dermatology demands that all practicing dermatologists have an understanding of the challenges and that they participate in the design of appropriate cost-effective strategies for the future. PMID- 7986129 TI - Erythroderma. Who, where, when, why, and how ... PMID- 7986130 TI - Bullae on the legs of an elderly man. Mycosis fungoides bullosa. PMID- 7986131 TI - Fever, maculopapular eruption, and lymphadenopathy. Angioimmunoblastic lymphadenopathy (AILD). PMID- 7986132 TI - Coalescing violaceous plaques forming leonine facies. Lymphocytoma cutis (pseudolymphoma). PMID- 7986133 TI - Rapidly progressing nodule in a patient with the acquired immunodeficiency syndrome. Primary cutaneous B-cell lymphoma. PMID- 7986134 TI - Use of animal skin substrates for indirect immunofluorescence diagnosis of subepidermal autoimmune bullous diseases. PMID- 7986135 TI - Laparoscopic ultrasonography. Enhancing minimally invasive surgery. PMID- 7986137 TI - Video-assisted thoracic surgery. Current state of the art. AB - OBJECTIVE: The author reviews the current state of the art of video-assisted thoracic surgery in the context of modern thoracic surgical practice. SUMMARY BACKGROUND DATA: Thoracoscopy has been a part of thoracic surgical practice for many years, but was used mainly for diagnosis of pleural disease. The development of laparoscopic cholecystectomy awakened a new interest in this technique and led to the development of many new therapeutic and diagnostic applications of video assisted thoracic surgery. METHODS: Current literature and the author's personal experience with more than 500 cases are reviewed. RESULTS: Video-assisted techniques have proven useful for the performance of a broad spectrum of thoracic surgical procedures. Patients may experience less pain and have a shorter hospital stay after a video-assisted procedure. Definitive proof of less morbidity when compared with the analagous open procedure remains to be determined. Patient acceptance has been high, and most thoracic surgeons use these techniques in their practice. CONCLUSIONS: Video-assisted thoracic surgical procedures have made a significant impact on the practice of thoracic surgery. Advantages and disadvantages of specific procedures remain to be definitively determined. Surgeons have learned these techniques and have kept morbidity to acceptance levels during the learning phase. Where these techniques ultimately fit into the overall practice remains to be determined as more experience is gained. PMID- 7986138 TI - Local anesthesia for inguinal hernia repair step-by-step procedure. AB - OBJECTIVE: The authors introduce a simple six-step infiltration technique that results in satisfactory local anesthesia and prolonged postoperative analgesia, requiring a maximum of 30 to 40 mL of local anesthetic solution. SUMMARY BACKGROUND DATA: For the last 20 years, more than 12,000 groin hernia repairs have been performed under local anesthesia at the Lichtenstein Hernia Institute. Initially, field block was the mean of achieving local anesthesia. During the last 5 years, a simple infiltration technique has been used because the field block was more time consuming and required larger volume of the local anesthetic solution. Furthermore, because of the blind nature of the procedure, it did not always result in satisfactory anesthesia and, at times, accidental needle puncture of the ilioinguinal nerve resulted in prolonged postoperative pain, burning, or electric shock sensation within the field of the ilioinguinal nerve innervation. METHODS: More than 12,000 patients underwent operations in a private practice setting in general hospitals. RESULTS: For 2 decades, more than 12,000 adult patients with reducible groin hernias satisfactorily underwent operations under local anesthesia without complications. CONCLUSIONS: The preferred choice of anesthesia for all reducible adult inguinal hernia repair is local. It is safe, simple, effective, and economical, without postanesthesia side effects. Furthermore, local anesthesia administered before the incision produces longer postoperative analgesia because local infiltration, theoretically, inhibits build up of local nociceptive molecules and, therefore, there is better pain control in the postoperative period. PMID- 7986136 TI - Superior staging of liver tumors with laparoscopy and laparoscopic ultrasound. AB - OBJECTIVE: The authors describe the technique of staging laparoscopy with laparoscopic contact ultrasonography in the preoperative assessment of patients with liver tumors, and assess its impact on the selection of patients for hepatic resection with curative intent. SUMMARY BACKGROUND DATA: Laparoscopy may be useful in the selection of patients with a variety of intra-abdominal malignancies for operative intervention. Laparoscopic ultrasonography is a new technique that combines the principles of high resolution intraoperative contact ultrasound with those of the laparoscopic examination, and thus, allows the laparoscopist to perform detailed assessment of the liver. METHODS: This study analyzes a cohort of 50 consecutive patients who were diagnosed as having potentially resectable liver tumors, and in whom staging laparoscopy was successfully undertaken. Laparoscopic ultrasonography was performed in 43 patients, and the impact of the ensuing findings on the decision to proceed to operative assessment of resectability is examined. The resectability rate in those patients assessed laparoscopically and subsequently submitted to laparotomy is compared with a preceding group of patients in whom no laparoscopic assessment was performed. RESULTS: Laparoscopy demonstrated factors precluding curative resection in 23 patients (46%). Laparoscopic ultrasonography identified liver tumors not visible during laparoscopy in 14 patients (33%), and provided staging information in addition to that derived from laparoscopy alone in 18/43 patients (42%). The resectability rate was significantly higher among those patients undergoing laparoscopic staging (93%) compared with those in whom operative assessment was undertaken without laparoscopy (58%). CONCLUSIONS: Staging laparoscopy with laparoscopic ultrasonography optimizes patient selection for liver resection with curative intent. PMID- 7986139 TI - The effect of length of stay on complications. PMID- 7986140 TI - The effect of complications on length of stay. AB - OBJECTIVES: The authors determined the effect of complications on length of stay (LOS) in surgical patients. SETTING: From 1987 to 1990, in the Professional General Surgical Unit of Royal Victoria Hospital, a retrospective survey was conducted on 5128 consecutively admitted patients with 396 different diagnosis; 228 different operations were examined. MAIN OUTCOME MEASURES: Patient LOS during a 3-year period in a general surgical ward was analyzed from hospital activity analysis, case notes, ward audit notes, and sepsis audit notes. Readmission rates for complications in patients with a short LOS were examined. Comparison were made between LOS and age, type of surgery, and complication type. RESULTS: Pressure on beds resulting from an increased demand on surgical care decreases patient's hospital LOS; increasing age increases LOS. In general, complications double the average LOS. The authors calculated that a surgical complication can be given a numerical ratio that directly reflects the severity of the complication and increases the patient's LOS. The ration of the infective complication corresponds with the clinical severity of the complication. However, a short LOS may lead to readmission of patients for further treatment. For patients readmitted with complications, 41% had been discharged earlier than the average LOS for their diagnosis. CONCLUSION: Length of stay is increased by complications and can be used to implement discharge planning in general surgical patients. Furthermore, a complication of their treatment can be given a numerical ratio that corresponds to the clinical severity of the complication and the increased LOS in hospital. PMID- 7986141 TI - Of mice and men. Honesty and integrity in medicine. PMID- 7986142 TI - Candida colonization and subsequent infections in critically ill surgical patients. AB - OBJECTIVE: The authors determined the role of Candida colonization in the development of subsequent infection in critically ill patients. DESIGN: A 6-month prospective cohort study was given to patients admitted to the surgical and neonatal intensive care units in a 1600-bed university medical center. METHODS: Patients having predetermined criteria for significant Candida colonization revealed by routine microbiologic surveillance cultures at different body sites were eligible for the study. Risk factors for Candida infection were recorded. A Candida colonization index was determined daily as the ratio of the number of distinct body sites (dbs) colonized with identical strains over the total number of dbs tested; a mean of 5.3 dbs per patient was obtained. All isolates (n = 322) sequentially recovered were characterized by genotyping using contour-clamped homogeneous electrical field gel electrophoresis that allowed strain delineation among Candida species. RESULTS: Twenty-nine patients met the criteria for inclusion; all were at high risk for Candida infection; 11 patients (38%) developed severe infections (8 candidemia); the remaining 18 patients were heavily colonized, but never required intravenous antifungal therapy. Among the potential risk factors for candida infection, three discriminated the colonized from the infected patients--i.e., length of previous antibiotic therapy (p < 0.02), severity of illness assessed by APACHE II score (p < 0.01), and the intensity of Candida spp colonization (p < 0.01). By logistic regression analysis, the latter two who were the independent factors that predicted subsequent candidal infection. Candida colonization always preceded infection with genotypically identical Candida spp strain. The proposed colonization indexes reached threshold values a mean of 6 days before Candida infection and demonstrated high positive predictive values (66 to 100%). CONCLUSIONS: The intensity of Candida colonization assessed by systematic screening helps predicting subsequent infections with identical strains in critically ill patients. Accurately identifying high-risk patients with Candida colonization offers opportunity for intervention strategies. PMID- 7986143 TI - The orderly progression of melanoma nodal metastases. AB - OBJECTIVE: The aim of this study was to determine the order of melanoma nodal metastases. SUMMARY BACKGROUND DATA: Most solid tumors are thought to demonstrate a random nodal metastatic pattern. The incidence of skip nodal metastases precluded the use of sampling procedures of first station nodal basins to achieve adequate pathological staging. Malignant melanoma may be different from other malignancies in that the cutaneous lymphatic flow is better defined and can be mapped accurately. The concept of an orderly progression of nodal metastases is radically different than what is thought to occur in the natural history of metastases from most other solid malignancies. METHODS: The investigators performed preoperative and intraoperative mapping of the cutaneous lymphatics from the primary melanoma in an attempt to identify the "sentinel" lymph node in the regional basin. All patients had primary melanomas with tumor thicknesses > 0.76 mm and were considered candidates for elective lymph node dissection. The sentinel lymph node was harvested and submitted separately to pathology, followed by a complete node dissection. The null hypothesis tested was whether nodal metastases from malignant melanoma occurred in equal proportions among sentinel and nonsentinel nodes. RESULTS: Forty-two patients met the criteria of the protocol based on prognostic factors of their primary melanoma. Thirty-four patients had histologically negative sentinel nodes, with the rest of the nodes in the basin also being negative. Thus, there were no skip metastases documented. Eight patients had positive sentinel nodes, with seven of the eight having the sentinel node as the only site of disease. In these seven patients, the frequency of sentinel nodal metastases was 92%, whereas none of the higher nodes had documented metastatic disease. Nodal involvement was compared between the sentinel and nonsentinel nodal groups, based on the binomial distribution. Under the null hypothesis of equality in distribution of nodal metastases, the probability that all seven unpaired observations would demonstrate that involvement of the sentinel node is 0.008. CONCLUSIONS: The data presented demonstrate that nodal metastases from cutaneous melanoma are not random events. The sentinel lymph nodes in the lymphatic basins can be mapped and identified individually, and they have been shown to contain the first evidence of melanoma metastases. This information can be used to revolutionize melanoma care so that only those patients with evidence of nodal metastatic disease are subjected to the morbidity and expense of a complete node dissection. Because sentinel node histology accurately reflects the histology of the remainder of the lymphatic basin, information gained from the sentinel node biopsy can be used as a prognostic factor for melanoma. These findings demonstrate effective pathologic staging, no decrease in standards of care, and a reduction of morbidity with a less aggressive, rational surgical approach. PMID- 7986144 TI - Detection of submicroscopic lymph node metastases with polymerase chain reaction in patients with malignant melanoma. AB - BACKGROUND: The presence or absence of lymph node metastases in patients with malignant melanoma is the most powerful prognostic factor for predicting survival. If regional nodal metastases are found, the 5-year survival for the patient decreases approximately 50%. If the presence or absence of regional nodal metastases will determine which patients receive formal dissections or which patients enter adjuvant trials, then a technique is needed to accurately screen lymph node samples for occult disease. Routine histopathologic examination routinely underestimates the number of patients with metastases. This study was initiated to develop a highly sensitive clinically applicable method to detect micrometastases by examining lymph nodes for the presence of tyrosinase messenger RNA (mRNA). The hypothesis was that if mRNA for tyrosinase is found in the lymph node preparation, that finding is good evidence that metastatic melanoma cells are present. METHODS: The assay is accomplished using the combination of reverse transcription and double-round polymerase chain reaction (RT-PCR). The amplified samples are examined on a 2% agarose gel and tyrosinase cDNA is seen as a 207 base pair fragment. Lymph node preparations from 29 patients who were clinically stage I and II and undergoing elective node dissections were analyzed both by standard pathologic staining and RT-PCR. RESULTS: Eleven of 29 lymph node (38%) samples from 29 patients with intermediate thickness melanoma were pathologically positive. Nineteen of the 29 lymph node preparations (66%) were RT-PCR-positive, and these included all of the pathologically positive samples, so that the false negative rate was 0. In a spiking experiment, one SK-Mel-28 melanoma cell in a background of one million normal lymphocytes could be detected, thus indicating the sensitivity of this method. In addition, analysis by restriction enzyme mapping showed that the amplified 207-bp PCR product produced is part of the tyrosinase gene sequence. CONCLUSION: The RT-PCR method is an extremely sensitive, reproducible, and efficient technique for the identification of micrometastases in patients with melanoma and could be widely applicable. If clinical correlation is obtained, staging of the melanoma patient becomes more accurate, and treatment becomes more standardized and rational, because all those patients who have evidence of nodal disease can be identified so that they may benefit from more extensive surgery (formal node dissections) or adjuvant therapies. Based on these results, RT-PCR could be a powerful tool to detect micrometastatic melanoma. PMID- 7986145 TI - Clinical implications of cervical lymph node metastasis patterns in thoracic esophageal cancer. AB - OBJECTIVE: The authors attempt to clarify the clinical implications of cervical lymph node metastases from thoracic esophageal cancers. SUMMARY BACKGROUND DATA: Cervical lymph node metastases from thoracic esophageal cancer have been considered to be incompatible with curative resection. However, recent studies have demonstrated that cure is achievable in patients with such metastases. METHODS: Patterns of esophageal cancer metastasis to the cervical nodes and long term results after tumor resection were investigated in 23 patients undergoing bilateral cervical lymphadenectomy for treatment of thoracic esophageal cancer. RESULTS: The number of positive nodes per patient was significantly greater (p < 0.05) in lower esophageal cancers (median: 15) than in upper or mid esophageal cancers (median: 2.5). Simultaneous metastases to three nodal regions (the neck, mediastinum, and abdomen) were significantly more common (p < 0.001) in lower esophageal tumors (88.9%) than in upper and mid esophageal lesions (7.1%). Although the overall 5-year survival rate was 16.5%, long-term survival was achieved only in patients with upper or mid esophageal cancer. PMID- 7986146 TI - Weight loss and dietary intake after vertical banded gastroplasty and Roux-en-Y gastric bypass. AB - OBJECTIVE: The purpose of this study was to learn whether preoperative eating habits can be used to predict outcome after vertical banded gastroplasty (VBG) and Roux-en-Y gastric bypass (RYGB). BACKGROUND SUMMARY: Several independent randomized and sequential studies have reported significantly greater weight loss after RYGB in comparison with VBG. Although the mechanism responsible for weight loss after both procedures is restriction of intake rather than malabsorption, the relationships between calorie intake, food preferences, and postoperative weight loss are not well defined. METHODS: During the past 5 years, 138 patients were prospectively selected for either VBG or RYGB, based on their preoperative eating habits. All patients were screened by a dietitian who determined total calorie intake and diet composition before recommending VBG or RYGB. Thirty patients were selected for VBG; the remaining 108 patients were classified as "sweets eaters" or "snackers" and had RYGB. Detailed recall diet histories also were performed at each postoperative visit. RESULTS: Early morbidity rate was zero after VBG versus 3% after RYGB. There were no deaths. Mean follow-up was 39 +/- 11 months after VBG and 38 +/- 14 months after RYGB. Mean weight loss peaked at 74 +/- 23 lb at 12 months after VBG and 99 +/- 24 lb at 16 months after RYGB (p < or = 0.001). Twelve of 30 VBG patients lost > or = 50% of their excess weight versus 100 of 108 RYGB patients (p < or = 0.0001). Milk/ice cream intake was significantly greater postoperatively in patients who underwent VBG versus patients who underwent RYGB after 6 months (p < or = 0.003), whereas solid sweets intake was significantly greater after VBG during the first 18 months postoperatively (p < or = 0.004). Revision of VBG was performed in 6 of 30 patients (20%) for complications or poor weight loss, whereas only 2 of 108 patients who underwent RYGB required surgical revisions (p < or = 0.001). CONCLUSIONS: These data show that VBG adversely alters postoperative eating behavior toward soft, high-calorie foods, resulting in problematic postoperative weight loss. Conversely, RYGB patients had significantly greater weight loss despite inferior preoperative eating habits. The high rate of surgical revision in conjunction with inconsistent postoperative weight loss has led us to no longer recommend VBG as treatment for morbid obesity. PMID- 7986147 TI - Blood transfusions and local tumor recurrence in colorectal cancer. Evidence of a noncausal relationship. AB - OBJECTIVE: The authors analyzed the effect of blood transfusions on the pattern of colorectal cancer recurrence. BACKGROUND: Retrospective studies suggest that blood transfusions are associated with a poor prognosis in patients who undergo operations for colorectal malignancies. In a previously published, randomized trial, it was investigated whether autologous blood transfusions could overcome this putative detrimental effect. However, this did not appear to be the case. METHODS: In the current study, the authors analyzed the patterns of recurrence in 420 patients who underwent curative operations for colorectal cancer. RESULTS: Patients who did not require transfusions (N = 143) had significantly better disease-free survival than those who did need transfusions (N = 277); percentages at 4 years were 73% and 59%, respectively (p = 0.001). No difference was found between both groups in comparing cumulative percentages of patients having metastases; percentages at 4 years were 25% in the group that did not undergo transfusion and 27% in the transfused group. The percentage of cases having local recurrence, however, was significantly increased (p = 0.0006) in the transfused group as compared with the group that did not undergo transfusion; percentages at 4 years were 20% and 3%, respectively. The groups of patients receiving only allogeneic, only autologous, or both types of transfusions all had a significantly higher incidence of local recurrence than the patients who did not receive transfusions, but no differences were found between these three groups. CONCLUSIONS: These findings suggest that the association between blood transfusions and prognosis in colorectal cancer is a result of the circumstances that necessitate transfusions, leading to the development of local recurrences, but not of distant metastases. PMID- 7986148 TI - Secretory immunoglobulin A, intestinal mucin, and mucosal permeability in nutritionally induced bacterial translocation in rats. AB - OBJECTIVE: The authors investigated the role of mucin and secretory immunoglobulin A (slgA) in a model of nutritionally induced bacterial translocation. BACKGROUND: Parenteral and certain elemental diets have been shown to impair intestinal barrier function, whereas fiber has been shown to protect against nutritionally induced bacterial translocation. However, the factors responsible for these phenomenon have not been fully determined. METHODS: Intestinal mucin levels, mucosal protein content, slgA, intestinal morphology, and permeability to horseradish peroxidase, bacterial translocation, and intestinal bacterial population levels were measured in rats 7 days after receiving total parenteral nutrition (TPN) solution (28% glucose, 4.25% amino acids; 307 kcal/kg/day) enterally (ORAL-TPN) or parenterally (IV-TPN) with or without enteral bulk fiber supplementation. Chow-fed rats served as control subjects. RESULTS: The incidence of bacterial translocation in the ORAL-TPN and IV-TPN groups was reduced significantly by the provision of fiber (p < 0.05). Mucosal protein, slgA, and insoluble mucin levels were decreased in the jejunum of the ORAL-TPN and IV-TPN groups, with mucosal protein levels being decreased to a greater extent than slgA or mucin. Although similar decreases in these parameters were observed in the fiber-fed groups, fiber appeared to improve intestinal barrier function as measured by horseradish peroxidase permeability. CONCLUSIONS: The provision of bulk-forming fiber improves intestinal barrier function as measured by peroxidase permeability and bacterial translocation, but does not restore mucosal protein content, intestinal mucin, or slgA levels to normal. PMID- 7986149 TI - Surgical treatment of diabetes mellitus with pancreas transplantation. AB - OBJECTIVE: The authors compared results and morbidity in insulin-dependent diabetes mellitus (IDDM) patients undergoing preemptive pancreas transplantation (PTx) either before dialysis or before the need for a kidney transplant with IDDM patients undergoing conventional combined pancreas-kidney transplantation (PKT) after the initiation of dialysis therapy. SUMMARY BACKGROUND DATA: Combined PKT has become accepted generally as the best treatment option in carefully selected IDDM patients who either are dependent on dialysis or for whom dialysis is imminent. With improving results, the timing of PKT relative to the degree of nephropathy is evolving. However, it is not well established that the advantages of preemptive PTx can be achieved without incurring a detrimental effect on graft function or survival. METHODS: Over a 4-year study period, data on the following 3 recipient groups were collected prospectively and analyzed retrospectively: 1) 38 IDDM patients undergoing combined PKT while on dialysis (PKT:D); 2) 44 IDDM patients undergoing preemptive PKT before dialysis (PKT:ND); and 3) 20 IDDM patients undergoing solitary PTx. All patients underwent whole organ PTx with bladder drainage and were treated with quadruple immunosuppression. RESULTS: Actuarial 1-year patient survival is 100%, 98%, and 93%, respectively. One-year actuarial PTx survival (insulin-independence) is 92%, 95%, and 78%, respectively. The incidence of rejection, infection, operative complications, readmissions, and total hospital days was similar in the three groups. Long-term renal and pancreas allograft function and quality of life were similarly comparable. Rehabilitation potential favored the solitary PTx and PKT:ND groups. CONCLUSIONS: Preemptive PKT or solitary PTx performed earlier in the course of diabetes is associated with good results, facilitated rehabilitation, and may prevent further diabetic complications. PMID- 7986150 TI - Glucocorticoid receptor blockade reverses postinjury macrophage suppression. AB - OBJECTIVES: To study the effects of the stress-induced surge of endogenous glucocorticoids on macrophage function and the role of inhibiting glucocorticoids with a receptor antagonist, mifepristone (RU 486). DESIGN: One hundred thirty female Swiss-Webster mice were randomly assigned to either injury by femur fracture or uninjured anesthesia control in this intervention study. SETTING: A university-based surgical laboratory and animal facility. INTERVENTION: Injured mice were randomized to receive either the glucocorticoid receptor antagonist mifepristone (10 mg/kg by oral gavage) or its vehicle. Mifepristone or its vehicle were given either 2 hours before or 2 hours after the injury. MAIN OUTCOME MEASURES: Peritoneal macrophages were harvested 24 hours after the injury. Macrophages were assayed for the stimulated (phorbol myristate acetate, 1 microgram/mL) production of superoxide anion, secretion of interleukin-6, tumor necrosis factor alpha, and prostaglandin E2 in response to endotoxin (lipopolysaccharide at 10 micrograms/mL) and killing of Candida albicans. RESULTS: Pretreatment with mifepristone significantly prevented or reduced suppression of several macrophage functions following injury, including superoxide production and C albicans killing. Treatment after the injury preserved only C albicans. Mifepristone failed to block the increased secretion of prostaglandin E2 after injury. CONCLUSION: Pretreatment with mifepristone before an injury prevented suppression of several macrophage functions. Further studies are required on the effects of glucocorticoid inhibition on other aspects of the immune and metabolic responses to injury to define the potential clinical applications of mifepristone trauma. PMID- 7986151 TI - The pulmonary effect of nitric oxide synthase inhibition following endotoxemia in a swine model. AB - OBJECTIVE: To evaluate the pulmonary effect of treatment with N-nitro-L-arginine methyl ester (NAME) with and without inhaled nitric oxide (NO) in a swine model of endotoxemia. DESIGN: Randomized controlled trial. SETTING: Laboratory. INTERVENTIONS: Following a 20-minute intravenous infusion of Escherichia coli lipopolysaccharide (LPS) (200 micrograms/kg), animals were resuscitated with saline solution (1 mL/kg per minute) and observed for 3 hours while mechanically ventilated (fraction of inspired oxygen [FIO2], 0.6; tidal volume, 12 mL/kg; positive end-expiratory pressure, 5 cm H2O). Group 1 (LPS, n = 6) received no additional treatment; group 2 (NAME, n = 5) received NAME (3 mg/kg per hour) for the last 2 hours; group 3 (NO, n = 6) received NAME (3 mg/kg per hour) and inhaled NO (40 ppm) for the last 2 hours; and group 4 (control, n = 5) received only saline solution without LPS. MAIN OUTCOME MEASURES: Cardiopulmonary variables and blood gases were measured serially. The multiple inert gas elimination technique was performed at 3 hours. The wet-to-dry lung weight ratio was measured following necropsy. RESULTS: Administration of LPS resulted in pulmonary arterial hypertension, pulmonary edema, and hypoxemia with increased ventilation perfusion ratio mismatching. None of these changes were attenuated by NAME treatment alone but all were significantly improved by the simultaneous administration of inhaled NO. CONCLUSIONS: Systemic NO synthase inhibition failed to restore hypoxic pulmonary vasoconstriction following LPS administration. The deleterious effects of endotoxemia on pulmonary function can be improved by inhaled NO but not by systemic inhibition of NO synthase. PMID- 7986153 TI - The local role of tumor necrosis factor alpha in the modulation of neutrophil function at sites of inflammation. AB - OBJECTIVE: To examine the hypothesis that tumor necrosis factor alpha (TNF-alpha) is an important local modulator of neutrophil function in the inflammatory microenvironment. DESIGN: In vitro studies of host defense. PATIENTS: A volunteer sample of healthy subjects. INTERVENTION: Exudative neutrophils were collected from skin-blister chambers and functionally compared with blood neutrophils. METHODS: Tumor necrosis factor alpha levels at sites of inflammation and neutrophil exudation were determined and compared with serum concentrations. Flow cytometry was used to evaluate neutrophil microbicidal activity and N-formyl methionyl-leucyl-phenylalanine-induced changes in intracellular calcium and superoxide production. In vitro TNF-alpha was used to evaluate the nature and dose response of TNF-alpha-induced changes in neutrophil function. RESULTS: Exudative neutrophils have an increased responsiveness to subsequent N-formyl methionyl-leucyl-phenylalanine stimulation, as determined by changes in intracellular calcium. Microbicidal activity and superoxide production are also up-regulated compared with circulating neutrophils. The exudative microenvironment contains TNF-alpha at local levels that are capable of significantly enhancing neutrophil host defense. CONCLUSIONS: Tumor necrosis factor alpha may serve to enhance neutrophil function at sites of inflammation. Neutrophils become more cytotoxic and have an enhanced ability to respond to weak environmental signals. PMID- 7986152 TI - Immune function in patients undergoing open vs laparoscopic cholecystectomy. AB - BACKGROUND: Abnormal release of inflammatory mediators following surgical injury is associated with immunological alteration, which may predispose to sepsis. Laparoscopic surgery is associated with reduced postoperative complications, but mechanisms are unclear. We hypothesized that early recovery following laparoscopic surgery may relate to minimal impairment of immune function. DESIGN: Analysis of the temporal immune responses in two similar groups of patients randomized to open (n = 22) vs laparoscopic (n = 22) cholecystectomy. Patients were matched for age, height, weight, and operation time. Immune parameters, including monocyte superoxide anion (O2-) and tumor necrosis factor release, neutrophil O2- levels and chemotaxis, total white blood cell counts, partial arterial oxygen pressure, and serum cortisol and C-reactive protein levels were assessed preoperatively and on postoperative days 1 and 3. RESULTS: There were significant increases (P < .001) in monocyte release of O2- and tumor necrosis factor, neutrophil release of O2- and chemotaxis, and white blood cell count in the open vs laparoscopic cholecystectomy study groups, with a concommitant decrease in partial arterial oxygen pressure. These findings correlated with significantly higher postoperative septic complications in the open cholecystectomy group (P < .05). There were no significant differences in either plasma cortisol or C-reactive protein levels between groups. All measurements were carried out in a blinded fashion. CONCLUSIONS: This study demonstrates that laparoscopic surgery appears to be associated with similar metabolic responses compared with open surgery, while immune parameters vary greatly between groups. The beneficial effects of laparoscopic surgery may relate, in part, to preservation of immune function in the postoperative period. PMID- 7986154 TI - The role of programmed cell death (apoptosis) in thymic involution following sepsis. AB - OBJECTIVE: To test the hypothesis that thymic involution following peritoneal sepsis is secondary to thymocyte programmed cell death. DESIGN: We investigated the temporal response of thymic weight and thymic DNA fragmentation following peritoneal sepsis induced by cecal ligation and puncture in a rat model. We investigated the possible role of decreased interleukin (IL)-2 synthesis in the induction of apoptosis using rat thymocytes in primary culture. Finally, we studied IL-2 gene expression and IL-2 protein synthesis in phytohemagglutinin and IL-1 beta-treated thymocytes derived from the cecal ligation and puncture model of sepsis. RESULTS: We demonstrated that (1) there is a significant decrease in thymic weight and an increase in thymic DNA fragmentation with the characteristic apoptotic DNA "ladder" fragmentation pattern on agarose gel electrophoresis following peritoneal sepsis; (2) thymocytes in primary culture sustain a significant increase in thymocyte apoptosis following IL-2 withdrawal; and (3) peritoneal sepsis results in inhibition of phytohemagglutinin and IL-1 beta induced thymocyte IL-2 messenger RNA accumulation and protein synthesis. CONCLUSIONS: Thymic involution following peritoneal sepsis is associated with increased thymocyte programmed cell death. Thymocyte apoptosis induced by sepsis may be the result, in part, of inhibition of IL-2 gene expression. PMID- 7986155 TI - Macrophage endotoxin tolerance. Tumor necrosis factor and interleukin-1 regulation by lipopolysaccharide pretreatment. AB - OBJECTIVE: To correlate cytokine gene expression with the release of protein product by murine peritoneal macrophages rendered tolerant by sequential endotoxin stimulation in vitro. DESIGN: In vitro investigation of the regulation of endotoxin-stimulated cytokine production following endotoxin pretreatment using cytokine bioassays, polymerase chain reaction, and Northern blot analyses. SETTING: In vitro cell culture model of sequential endotoxin stimulation of murine macrophages. INTERVENTIONS: Macrophages were pretreated with 0 or 100 ng/mL of lipopolysaccharide (LPS1) for 24 hours and then stimulated with 0 or 100 ng/mL of LPS (LPS2) for 4 or 24 hours. After stimulation, supernatant tumor necrosis factor (TNF) and interleukin-1 (IL-1) levels were measured by bioassay. Total RNA was extracted and messenger RNA (mRNA) corresponding to TNF and IL-1 was amplified by reverse transcription-polymerase chain reaction or analyzed by Northern blot. RESULTS: Endotoxin pretreatment resulted in the augmentation of IL 1 (mean +/- SD, 78 +/- 9 vs 596 +/- 42 pg/mL, P < .01) and the inhibition of TNF (274 +/- 63 vs 61 +/- 3 pg/mL, P < .01) release 4 hours after stimulation with 100 ng/mL of LPS2. A similar pattern of cytokine release was observed 24 hours after LPS2 stimulation. Pretreatment produced an increased IL-1 message in response to 100 ng/mL of LPS2. The TNF message was detectable in all groups receiving LPS2 alone, but the highest levels of TNF mRNA were seen in LPS1 pretreated cells stimulated with LPS2. CONCLUSIONS: Endotoxin pretreatment produced increased IL-1 message that paralleled the augmentation of IL-1 protein, whereas abundant TNF message was present even though TNF protein release was significantly inhibited. In this model of in vitro endotoxin tolerance, pretreatment initiates divergent pathways of cytokine regulation. PMID- 7986156 TI - Nitric oxide inhibition normalizes splenocyte interleukin-10 synthesis in murine thermal injury. AB - OBJECTIVE: To examine the effect of nitric oxide inhibition on cytokine production and immunologic function in a murine thermal-injury and an alcohol (ETOH)-ingestion model. DESIGN: Randomized controlled experiment. SETTING: University surgical research laboratory. ANIMALS: Forty male Balb/C mice. INTERVENTIONS: Animals were randomized to four groups: normal saline solution sham (NS-sham), ETOH-sham, NS-burn, and ETOH-burn. Animals received 20% ETOH or NS daily for 14 days by gavage. A 20% full-thickness burn was induced 4 hours after the last dose of ETOH or NS was administered. Animals were killed 4 days after the burn was induced. MAIN OUTCOME MEASURES: Splenocytes were harvested and stimulated with the mitogens lipopolysaccharide or concanavalin A. These mitogen stimulated splenocyte cultures had the addition of exogenous N-monomethyl-L arginine (2.5 or 10 micrograms/mL), a nitric oxide synthase inhibitor. Splenocyte production of interleukin-10 (IL-10), interferon-gamma, nitrite, and prostaglandin E2 were measured, and lymphocyte proliferative response was examined. RESULTS: Interleukin-10 and interferon-gamma production were significantly suppressed in thermal injury, and lymphocyte proliferative response was markedly reduced. Exogenous N-monomethyl-L-arginine normalized splenocyte IL 10 production in a dose-dependent manner in NS-burn and ETOH-burn groups, improved lymphocyte proliferative response, and significantly decreased splenocyte nitrite production. Interferon-gamma release was not up-regulated by N monomethyl-L-arginine. CONCLUSIONS: Thermal injury is associated with a suppression of splenocyte IL-10 production and lymphocyte proliferative response. Inhibition of nitric oxide synthesis normalized IL-10 production and significantly improved splenocyte proliferative response. These data suggest that nitric oxide is an important modulator of cytokine regulation and immunologic function in thermal injury, thereby ultimately influencing host defense. PMID- 7986157 TI - The role of cyclic adenosine monophosphate in the suppression of cellular immunity after thermal injury. AB - BACKGROUND AND OBJECTIVE: Cyclic adenosine monophosphate (cAMP) is an intracellular second messenger that is known to convey inhibitory signals for T cell proliferation and function. We investigated the association between this molecule and the profound immunosuppression that accompanies thermal injury. DESIGN: Mice were randomized into two groups: one group was subjected to a 20% full-thickness scald burn; the second to a sham burn (control). The mice were killed on days 4, 7, or 10 after the burn injury and splenocytes were pooled and cultured for 15 minutes in the presence or absence of prostaglandin E2 (PGE2). RESULTS: Levels of cAMP in splenocytes were significantly elevated on day 7 after burn in the burn group compared with the sham controls (P < .05, Wilcoxon Rank Sum Test). Incubation of splenocytes with PGE2 resulted in significantly greater levels of intracellular cAMP in cells from the burn group compared with controls on days 4, 7, and 10. Incubation of normal splenocytes with dibutyryl cAMP in the presence of concanavalin A significantly decreased cell proliferation and the production of interleukin-2. The decrease in interleukin-2 production was evident at the level of messenger RNA expression. Stimulation of splenocytes with a combination of phorbol ester and calcium ionophore, bypassing all membrane associated events prior to protein kinase C activation, reversed the inhibitory effects of dibutyryl cAMP. Incubation of splenocytes from burned animals with H 8, a selective inhibitor of cAMP-dependent protein kinases, restored the proliferative response to that of sham controls on days 4, 7, and 10 after thermal injury. CONCLUSIONS: These data indicate that elevated levels of intracellular cAMP, combined with an increased production of cAMP in response to circulating PGE2, may play a fundamental role in suppression of the immune response following thermal injury and that cAMP exerts its immunomodulatory effects prior to protein kinase C activation. PMID- 7986158 TI - Endotoxin stimulates interleukin-6 production in intestinal epithelial cells. A synergistic effect with prostaglandin E2. AB - OBJECTIVE: To test the hypothesis that endotoxin stimulates the release of interleukin-6 (IL-6) from intestinal epithelial cells and that this effect of endotoxin is regulated by prostaglandin E2 (PGE2). DESIGN: A rat intestinal crypt cell line, IEC-6, was cultured in the presence of lipopolysaccharide (LPS), 0.1 to 1.0 microgram/mL, and/or PGE2, 1 mumol/L. In other experiments, indomethacin, 20 mumol/L, was added to LPS-treated cells to block the effects of prostaglandins. Control wells contained medium alone. Levels of IL-6 were determined by the B9 murine hybridoma bioassay. Polymerase chain reaction was performed on RNA from control and LPS-treated cells to examine IL-6 message. RESULTS: Lipopolysaccharide and PGE2 induced IL-6 release from IEC-6 cells in a dose- and time-dependent fashion, and the substances interacted synergistically. Addition of indomethacin blunted the effect of endotoxin on IL-6 production, consistent with a stimulatory role of PGE2. Polymerase chain reaction demonstrated increased IL-6 messenger RNA in endotoxin-treated cells. CONCLUSIONS: Endotoxin and PGE2 stimulate IL-6 production in IEC-6 cells and interact synergistically. The endotoxin-stimulated IL-6 release may be regulated at the transcriptional level. PMID- 7986159 TI - Endotoxin-induced nitric oxide production in pulmonary artery endothelial cells is regulated by cytokines. AB - BACKGROUND: L-Arginine is the sole precursor of nitric oxide (NO). Bacterial lipopolysaccharide (endotoxin) (LPS) stimulates carrier-mediated L-arginine transport in porcine pulmonary artery endothelial cells (PAECs) through an autocrine pathway that involves interleukin-1 alpha (IL-1 alpha) and tumor necrosis factor alpha (TNF-alpha). OBJECTIVES: To determine if Escherichia coli LPS stimulates NO synthesis in PAECs and, if so, if LPS stimulation of NO production is also mediated by autocrine secretion of IL-1 alpha and TNF-alpha. DESIGN: Monolayers of PAECs were incubated with various concentrations of LPS, recombinant human TNF-alpha, or IL-1 alpha, and total nitrate-nitrite accumulation was measured at different time points with the Greiss reagent following cadmium reduction. Release of TNF-alpha and IL-1 alpha release by LPS stimulated PAECs were measured using the WEHI (for TNF-alpha) and A375.S2 (for IL 1 alpha) bioassays. The PAECs were then incubated with saline solution or LPS in the presence or absence of either a polyclonal antibody to human TNF or IL-1 receptor antagonist, and nitrate-nitrite accumulation was measured at 48 hours. RESULTS: Production of NO by PAECs was increased 230% by LPS (1 microgram/mL), 350% by TNF-alpha (1000 U/mL), and 240% by IL-1 alpha (1000 U/mL) (P < .05 vs control). The LPS-stimulated NO production was inhibited by IL-1 receptor antagonist (100 micrograms/mL) or antibody to TNF (10 micrograms/mL) to control levels (P < .05 vs LPS; difference vs saline solution was not significant). The LPS-stimulated TNF-alpha secretion by PAECs and TNF-alpha activity were maximal at 6 hours (400 +/- 42 pg/mL). The IL-1 alpha activity was not detectable in LPS stimulated PAECs by the A375.S2 bioassay. CONCLUSIONS: Endotoxin, TNF-alpha, and IL-1 alpha stimulated NO synthesis in PAECs. Endotoxin-stimulated NO synthesis through an autocrine pathway involving the cytokines TNF-alpha and IL-1 alpha. PMID- 7986160 TI - Lipolysis in burned patients is stimulated by the beta 2-receptor for catecholamines. AB - OBJECTIVE: To determine if the cardiovascular effects of excessive catecholamines could be selectively blocked in severely burned patients without adversely affecting protein or fat kinetics. DESIGN: Prospective cohort study. SETTING: A large tertiary care referral center in Galveston, Tex. PATIENTS: Sixteen patients with greater than 40% body surface area burns. INTERVENTIONS: Patients were randomly selected to receive propranolol hydrochloride, a nonselective beta 1- and beta 2-blocker, or metoprolol tartrate, a selective beta 1-blocker. MAIN OUTCOME MEASURES: Heart rate; rate-pressure product; rate of appearance of urea, glucose, and leucine; and leucine oxidation were measured before and after selective or nonselective beta-adrenergic blockade. RESULTS: Propranolol and metoprolol caused a significant decrease in heart rate, from a mean (+/- SD) of 143 +/- 15 to 115 +/- 11 and from 147 +/- 17 to 120 +/- 9 beats per minute, respectively, during the 5-day study period. Neither the rate of appearance of urea nor the rate of urea production were significantly altered by propranolol or metoprolol therapy. Only propranolol produced a significant decrease (P < .05) in the rate of appearance of glycerol, from a mean (+/- SD) of 5.54 +/- 0.62 to 3.07 +/- 0.7 mumol/kg per minute. The rate of appearance of leucine, used as an index of total body protein catabolism, was not significantly altered by either beta blocker. CONCLUSIONS: Selective beta 1-adrenergic blockade did not reduce lipolysis; however, a beta 1- and beta 2-adrenergic blockade significantly reduced lipolysis. Thus, the increased lipolysis, characteristic of severely burned patients, is caused by stimulation of the beta 2-adrenergic receptors for catecholamines. PMID- 7986161 TI - A decade of reduced gram-negative infections and mortality associated with improved isolation of burned patients. AB - OBJECTIVE: To compare the incidence of gram-negative bacteremia (GNB) and mortality in patients with large burns (> or = 20% of total body surface) hospitalized in either an open ward (OW) or a single-bed isolation (IW) environment. DESIGN: Retrospective cohort study. SETTING: The US Army Institute of Surgical Research, Burn Center, Ft Sam Houston, Tex. PATIENTS: Two thousand five hundred nineteen consecutive patients with large burns divided into two 10 year cohorts. Patients in the first cohort period were treated under OW conditions; patients in the second cohort period, under IW conditions. Infection (bacteremia) data were from a laboratory database. A microbial surveillance system was used to monitor patient isolation. Mortality was compared with predicted mortality derived by logistic regression of outcome, burn size, and age of patients without bacteremia in the study. MAIN OUTCOME MEASURES: Presence of GNB and survival. RESULTS: The incidence of GNB was higher in the OW cohort (31.2%) than the IW cohort (12.0%) (P < .001). The postinjury time of first GNB was delayed in the IW vs the OW cohort (28.9 days vs 11.8 days, respectively) (P < .001). For patients who had GNB in the OW cohort, mortality was higher than predicted (observed-predicted mortality ratio, 1.61) (P < .001). Such increased mortality was not present in the IW cohort. Multiple antibiotic-resistant gram negative pathogens were endemic in the OW cohort. There was no evidence of cross infection or endemic conditions with multiple antibiotic-resistant gram-negative pathogens in the IW cohort. CONCLUSION: Improvements in isolation of burned patients were associated with decreased incidence of GNB, delayed postinjury time of GNB, and improved survival. Improved survival is likely related to decreased susceptibility as a result of longer exposure to the benefits of treatment and wound closure. These results suggest that, in patients with severe burn injuries, gram-negative infections and the related mortality can largely be prevented. PMID- 7986162 TI - Characterization and impact of wound infection after pancreas transplantation. AB - OBJECTIVE: To characterize the incidence, microbial pathogenesis, risk factors, and impact of wound infection after pancreas transplantation. DESIGN: Retrospective analysis. SETTING: A large university hospital. PATIENTS: From January 1, 1990, to September 30, 1993, 197 patients underwent 207 consecutive pancreas transplantation procedures. MAIN OUTCOME MEASURES: Wound infection and patient and allograft survival rates at 1 year. RESULTS: Sixty-nine patients (33%) suffered wound infections: 21 (10%) were superficial; 31 (15%), deep; and 17 (8%), combined. Most (74%) wound infections were monomicrobial. Staphylococcus epidermidis and Candida species were the most common pathogens. Prolonged operating time, older donors, and enteric drainage were associated with higher wound infection rates. Deep and combined wound infections led to allograft loss despite subsequent salvage procedures. Combined wound infection was associated with significantly higher mortality. CONCLUSIONS: A deep wound infection should be an indication for allograft removal. Antifungal prophylaxis, stringent donor criteria, and delayed primary wound closure should lower the incidence of wound infection. PMID- 7986163 TI - Glutamine kinetics in burn patients. Comparison with hormonally induced stress in volunteers. AB - OBJECTIVE: To assess the acute and protracted adaptive response of peripheral glutamine kinetics to a severe injury. DESIGN: Comparison study. SETTING: Clinical research center at a university-affiliated hospital. PATIENTS: Six severely burned men and five young healthy men. INTERVENTIONS: The catabolic hormones epinephrine, cortisol, and glucagon were infused simultaneously into the femoral artery of five healthy volunteers, thus acutely simulating the hormonal milieu associated with a severe injury. MAIN OUTCOME MEASURES: Whole-body glutamine flux and peripheral glutamine kinetics were determined using glutamine labeled with nitrogen 15 and net balance measurements in patients 2 weeks following a severe burn injury. Identical measurements were made in the healthy volunteers before and following 4 hours of catabolic hormone infusion. RESULTS: Whole-body glutamine flux increased to a similar extent in both the burn patients and in volunteers following catabolic hormone infusion. In comparison with their basal kinetics, the hormonally simulated acute stress in the volunteers induced a significant efflux of glutamine from the leg by greatly increasing the rate of glutamine appearance. In contrast, burn patients had a significant decrease in their rate of glutamine appearance and achieved a similar net loss of glutamine from the leg only by a compensatory decrease in peripheral glutamine consumption. CONCLUSIONS: These findings suggest that in the acute stress response, skeletal muscle preferentially releases glutamine from its free intracellular pool. As this reserve becomes depleted, net glutamine efflux is maintained by decreasing its rate of muscle glutamine utilization. These results suggest a failure of muscle to augment de novo glutamine synthesis and support the conclusion that glutamine is a conditionally essential amino acid during critical illness. PMID- 7986164 TI - Activation of Kupffer cells in vivo following femur fracture. AB - OBJECTIVE: To test the hypothesis that Kupffer cells are activated after blunt femur fracture leading to altered hepatic oxygen (O2) consumption. DESIGN: Prospective randomized experimental trials. SETTING: Laboratory. MATERIALS AND METHODS: Male Sprague-Dawley rats underwent closed femur fracture with associated soft-tissue injury. Control animals received only anesthesia. After 30 minutes and 2 hours, livers were perfused and fixed. Tissue was processed for scanning and transmission electron microscopy. In separate experiments, hepatic O2 consumption was measured in isolated perfused livers 2 and 48 hours after femur fracture using a Clark-type electrode. Oxygen consumption was calculated from the influent-effluent concentration difference, flow rate, and liver weight. RESULTS: In femur-fractured animals, scanning electron microscopy revealed alterations in Kupffer cell surface characteristics, including increases in cell volume and complex foldings and extensions of the plasma membrane. Transmission electron microscopy showed internal vacuolization and dark-staining granule formation. The changes were more pronounced 2 hours after femur fracture. Hepatic O2 consumption increased significantly at both 2 and 48 hours after femur fracture. Morphologic and functional activation of Kupffer cells were not seen in control animals. CONCLUSION: In vivo ultrastructural evidence shows Kupffer cell activation after closed femur fracture. This activation is associated with increased hepatic O2 consumption, which is present at 2 hours and persists 48 hours following injury. The results suggest that Kupffer cell activation may be related to the acute phase response following trauma. PMID- 7986165 TI - Increased release of soluble tumor necrosis factor receptors into blood during clinical sepsis. AB - OBJECTIVES: To examine the kinetics of altered soluble tumor necrosis factor receptors (sTNFRs) released in patients with severe sepsis, their correlation with the morbidity and mortality of these patients, and the role of endotoxin to induce cleavage of sTNFRs. DESIGN: Soluble TNFR levels in plasma obtained from 40 patients with severe sepsis (mean [+/- SD] Acute Physiology and Chronic Health Evaluation [APACHE] II score, 27.9 +/- 7.0 points) on days 0, 1, 3, 5, and 10 after sepsis diagnosis were measured using specific enzyme-linked immunological binding assays and compared with levels in 75 control patients without infection. In addition, an ex vivo model consisting of lipopolysaccharide stimulation of human whole blood as a relevant physiological milieu was used. Blood from patients with sepsis and control patients was incubated in the presence or absence of lipopolysaccharide (1 mg/L) for 0, 1, 2, 4, 8, and 24 hours. Plasma levels of sTNFRs from both groups were determined using the enzyme-linked immunological binding assays. RESULTS: In patients with sepsis, plasma levels of both sTNFRs were markedly (P < .01) increased during the whole observation period, compared with those of control patients, and correlated (P < .001) with the simultaneously obtained APACHE II and multiple organ failure scores, as well as with mortality. Although incubation of whole blood with lipopolysaccharide increased the release of sTNFR p55 and p75 in both groups, sTNFR concentrations in blood from control patients remained low compared with those of patients with severe sepsis, despite stimulation of whole blood with a maximum lipopolysaccharide concentration. CONCLUSIONS: These data indicate that an enhanced release of sTNFRs during severe sepsis is not solely induced by endotoxin. Since the degree of increased sTNFR levels portended poorly for patient survival, elevated sTNFR levels may represent a good marker for severity of sepsis, thus predicting outcome. PMID- 7986166 TI - Treatment of burned mice with hyperbaric oxygen reduces mesenteric bacteria but not pulmonary neutrophil deposition. AB - OBJECTIVE: Hyperbaric oxygen (HBO) is used but unproven for many conditions, including burns. We hypothesized that HBO therapy might increase oxygen delivery to intestine during burn shock and decrease mucosal injury. SETTING: University research laboratory. DESIGN AND STUDY PARTICIPANTS: We studied the effects of HBO therapy (100% oxygen at 2.4 atm absolute) on mesenteric bacterial colonies (MBCs) in mice following 32% total body surface area burns. MBCs were counted 24 or 48 hours postburn by culturing mesenteric tissue. Intestinal histologic features were examined, acid-base balance was measured, and pulmonary neutrophil deposition was estimated by lung myeloperoxidase content. INTERVENTIONS: HBO delivered in a compression chamber. MAIN OUTCOME MEASURE: Numbers of mice with MBCs. RESULTS: With twice-daily HBO treatments, each treatment lasting 1.5 or 2 hours, fewer burned mice had MBCs. Three HBO treatments within 24 hours produced seizures, death, and increased numbers of mice with MBCs. Numbers of mice with MBCs were not influenced when compressed air (2.4 atm absolute) or 100% oxygen (1 atm absolute) was used. Villus histologic findings showed less damage in burned mice that received HBO therapy than in controls. Metabolic acidosis was not affected by HBO therapy, nor were lung myeloperoxidase levels. CONCLUSION: HBO therapy was associated with reduced numbers of mice with MBCs after burn injury and reduced histologic evidence of mucosal damage, but lung myeloperoxidase levels and metabolic acidosis were not affected. HBO therapy may increase oxygen delivery to ischemic intestine and improve cellular metabolism; alternatively, increased tissue oxygen may augment killing of translocated bacteria by phagocytic cells. HBO deserves further investigation for burn treatment, but because of the narrow therapeutic window and continued neutrophil sequestration in the lungs, we should proceed cautiously. PMID- 7986167 TI - Survival superiority of females with melanoma. PMID- 7986168 TI - Serum homocysteine levels in multiple sclerosis. PMID- 7986169 TI - Propranolol in prophylaxis of migraine. PMID- 7986170 TI - Parkinson and the plum tree. PMID- 7986171 TI - Iatrogenic neurological complications. PMID- 7986172 TI - Lower cognitive performance in normal older adult male twins carrying the apolipoprotein E epsilon 4 allele. AB - OBJECTIVE: Given the strong association of the apolipoprotein E (apoE) allele epsilon 4 with late-onset Alzheimer dementia or multi-infarct dementia, we tested whether normal older adult men with at least one epsilon 4 allele demonstrate subclinical changes in cognition and perform more poorly on tests of cognitive function compared with subjects without the epsilon 4 allele. DESIGN: Matched pair design of normal adult male (average age, 63 years) fraternal twins. SETTING: Subjects voluntarily participated on an outpatient basis at a research or medical center facility. PARTICIPANTS: Members of the National Heart, Lung, and Blood Institute twin panel third examination previously genotyped for apoE. MAIN OUTCOME MEASURE: Education-adjusted scores on several neuropsychological tests were compared in twins discordant for the apoE epsilon 4 allele. Subjects with documented cerebrovascular disease were excluded. RESULTS: Among 20 fraternal twin pairs discordant for the presence of epsilon 4, twins with the epsilon 4 allele demonstrated poorer mean performance than their co-twins without the epsilon 4 allele. This relationship was also noted cross-sectionally where age- and education-adjusted scores of 50 individual twin subjects with at least one epsilon 4 allele demonstrated poorer performance compared with 138 individual twins without an epsilon 4 allele. CONCLUSIONS: The apoE epsilon 4 allele may be associated with decreased cognitive function in discordant twin pairs. Our results suggest that epsilon 4 may represent a potential marker for accelerated cognitive aging and such individuals may be at greater risk for development of late-onset Alzheimer dementia or multi-infarct dementia. PMID- 7986173 TI - A large Swedish family with Alzheimer's disease with a codon 670/671 amyloid precursor protein mutation. A clinical and genealogical investigation. AB - OBJECTIVE: To describe clinical and genealogic features in a Swedish family with Alzheimer's disease with a double mutation of the amyloid precursor protein gene at codon 670/671 and to study the effects of anticipation and imprinting. DESIGN: Interviews with relatives, clinical investigations of the diseased, pedigree analysis, studies of medical records, and comparison with other families affected by Alzheimer's disease with amyloid precursor protein mutations. SETTING: The Alzheimer's Disease Research Centre, Department of Clinical Neuroscience, Section of Geriatric Medicine, Karolinska Institute, Huddinge (Sweden) University Hospital. PATIENTS AND OTHER PARTICIPANTS: Individuals with the amyloid precursor protein codon 670/671 mutation and their relatives (N = 66). RESULTS: The trait was traced through eight generations, and an autosomal dominant inheritance with very high penetrance was observed. Onset occurred between 44 and 61 years of age (mean, 53 years). The mean duration of disease was 8.5 years (range, 3 to 13 years). The earliest clinical manifestations were deficits in memory function and abstract reasoning. Myoclonic jerks and seizures were common symptoms late in the disease. Anticipation and imprinting effects were not found in this family. CONCLUSIONS: The disease in this family has a single origin--a double mutation in the amyloid precursor protein gene at codon 670/671 transmitted as an autosomal dominant trait. The wide range in age at onset and the clinical symptoms in this pedigree give a characteristic phenotype similar to that seen in some of the other pedigrees with amyloid precursor protein mutations. PMID- 7986174 TI - Reliability and validity of NINCDS-ADRDA criteria for Alzheimer's disease. The National Institute of Mental Health Genetics Initiative. AB - OBJECTIVE: To assess interrater reliability and validity of NINCDS-ADRDA (National Institute of Neurological and Communicative Diseases and Stroke/Alzheimer's Disease and Related Disorders Association) criteria for Alzheimer's disease (AD). DESIGN: A multisite reliability and validity study in which clinicians from each site diagnosed 60 case summaries yielding a preconsensus estimate of reliability and validity. A consensus conference was conducted for each disagreement, leading to a postconsensus estimate of validity. The criterion standard was a diagnosis of AD by autopsy. SETTING: Three academic medical centers. SUBJECTS: A convenience sample of 60 detailed case summaries, 40 with AD and 20 with other dementing disorders. MAIN OUTCOME MEASURES: The kappa coefficient, sensitivity, and specificity. RESULTS: The kappa coefficient for preconsensus agreement on a diagnosis of probable or possible AD vs non-AD was 0.51; the sensitivity of a diagnosis of probable or possible AD for a pathological diagnosis of AD was 0.81, and the specificity was 0.73. The postconsensus sensitivity was 0.83, and the specificity was 0.84. CONCLUSIONS: The results support the reliability and validity of NINCDS-ADRDA criteria and show that the consensus process may improve diagnostic accuracy. The cases are reviewed with a focus on the sources of diagnostic disagreements and errors and possible changes that might improve the accuracy of the criteria. PMID- 7986175 TI - Neurologic evaluation of the optimally healthy oldest old. AB - OBJECTIVE: Individuals aged 85 years or older (the "oldest old") are the fastest growing age group in the United States. Because there is little information characterizing expected neurologic function in this group, our goal was to determine clinical neurologic traits characteristic of the optimally healthy oldest old. DESIGN: Standardized neurologic evaluation findings of optimally healthy persons older than 84 years compared with those of equally healthy control subjects aged 65 to 74 years. SETTING: Community-based, longitudinal aging study. PARTICIPANTS: Community-residing, consecutively recruited volunteers who were screened for the absence of chronic disease or medication use. MAIN OUTCOME MEASURE: Standardized neurologic examination coded into ordinal or interval variables. RESULTS: Significant between-group differences were greatest for tests of mental status, sensory function (ie, smell, hearing, vibratory discrimination, and stereognosis), oculomotor function, distal movement speed, and balance. Discriminant function analysis suggests that of these changes, membership in the oldest group is best predicted by poor performance on clinical tests of balance (heel-toe walking and one-leg balancing with eyes closed), smell, and visual pursuit. CONCLUSIONS: Many neurologic signs appear with aging that cannot be attributed to disease, even in the very old. Deficits in balance, olfaction, and visual pursuit discriminate best between the aging changes of the healthy very old and changes seen in younger elderly persons. PMID- 7986176 TI - Factors affecting course and survival in Alzheimer's disease. A 9-year longitudinal study. AB - OBJECTIVE: To evaluate mean survival and to identify prognostic factors in a cohort of patients with Alzheimer's disease (AD). DESIGN: Multicentric 9-year cohort analytic study. SETTING: Seven neurology departments throughout Italy between April 1982 and January 1984. PATIENTS: We recruited a consecutive sample of 145 patients affected by probable AD (Multicenter Italian Study on Dementia protocol, National Institute of Neurological Disorders and Stroke-Alzheimer's Disease and Related Disorders Association criteria). Five were misdiagnosed, and 21 could not participate in the longitudinal study. The clinicodemographic characteristics of the 119 enrolled patients (49 men, 70 women; mean age, 64.7 years; SD, 4.1 years; mean duration of disease, 3.1 years; SD, 1.8 years) did not differ from those of the 26 excluded patients. All underwent extensive cliniconeuropsychological testing every 6 months for at least 2 years until the patient died or our survey ended (April 30, 1991). Mean follow-up was 5.1 years (SD, 2.5 years). MAIN OUTCOME MEASURES: Death, severe functional impairment (a score > or = 17 on the Blessed Dementia Scale), and severe cognitive impairment (a score of < or = 7 on the Information-Memory-Concentration Test). RESULTS: Survival curves obtained by the Kaplan-Meier method indicated that (1) patients with early- and late-onset disease (ie, before or after age 65 years) showed no difference either in relative survival or in time to reach predetermined functional and cognitive end points; (2) severely aphasic patients became profoundly demented significantly sooner than those with mild to moderate aphasia (P < .0001). Among clinicodemographic variables analyzed by a Cox model, severe language disability and functional loss proved to be the best predictors of death independent of age at onset or degree of dementia. CONCLUSIONS: Age at onset did not influence course and survival in AD. Severe aphasia appears to be the best predictor of death and unfavorable course. PMID- 7986177 TI - The malignancy of dementia. Predictors of mortality in clinically diagnosed dementia in a population survey of Shanghai, China. AB - OBJECTIVE: To evaluate the effect of dementing illnesses on the risk of dying, taking into account other conditions that would shorten survival. DESIGN: Five year follow-up of community survey of dementia. SETTING: Five-year data were obtained for the 3531 subjects, aged 65 years and older, who participated in the 1987 population survey of dementia in Shanghai, China. MAIN OUTCOME MEASURE: Time to death. Relative risks of dying were calculated for demographic variables, dementia diagnoses based on findings of clinical evaluations, and 15 reported prevalent medical conditions using the proportional hazards model. RESULTS: In those subjects aged 65 to 74 years, the mortality risk ratio was 5.4 (95% confidence interval, 2.0 to 14.6) for Alzheimer's disease and 7.2 (95% confidence interval, 3.6 to 14.4) for vascular dementia. The risk ratio for Alzheimer's disease was similar to the mortality risk ratio for cancer (5.6 [range, 2.9 to 10.9]). In this age group, dementing illnesses were uncommon, and few deaths were therefore attributable to the dementing illnesses. In those subjects aged 75 years and older, the mortality risk ratios were 2.8 (95% confidence interval, 2.1 to 3.6) for Alzheimer's disease, 3.5 (95% confidence interval, 2.4 to 5.1) for vascular dementia, and 3.6 (95% confidence interval, 2.0 to 6.7) for "other dementias." Because these dementing disorders were common in those subjects aged 75 years and older, 23.7% of the risk of death could be attributed to these disorders. CONCLUSIONS: Both Alzheimer's disease and vascular dementias are truly malignant and constitute major risk factors for death in persons older than 75 years. PMID- 7986178 TI - Neuropsychological deficits in vascular dementia vs Alzheimer's disease. Frontal lobe deficits prominent in vascular dementia. AB - OBJECTIVE: To detect neuropsychological differences between Alzheimer's disease (AD) and vascular dementia (VAD). DESIGN: Neuropsychological measures were compared in clinically defined AD and VAD patient groups. SETTING: Ambulatory and hospitalized patients were referred to a behavioral neurology clinic and to the neuropsychology department of a teaching hospital. PATIENTS: Consecutive, referred patients who fulfilled National Institute of Neurological Disorders and Stroke/Alzheimer's Disease and Related Disorders Association and Diagnostic and Statistical Manual of Mental Disorders, Revised Third Edition, criteria for AD and VAD were selected to participate in the study based on the history and clinical findings. A modified ischemic score of 3 or less was an independent selection criterion for AD (n = 103) and a score of 4 or more for VAD (n = 25). Computed tomography or magnetic resonance imaging was used to exclude other structural causes. Patients with cognitive changes related directly to a stroke were excluded. Patients were matched for age, education, age at onset, and severity of dementia. MEASURES: The variable measures were the subtests of the Wechsler Adult Intelligence Scale-Revised (WAIS-R), Wechsler Memory Scale Revised, Mattis Dementia Rating Scale (MDRS), and Western Aphasia Battery (WAB). Patients were further stratified into mild and severe dementia categories, based on their performance on the MDRS. RESULTS: Variables that were significantly different were selected for discriminant function analysis. The Writing subtest of the WAB, the Picture Arrangement subtest of the WAIS-R, and the Motor Performance subtest of the MDRS were the best discriminators of AD and VAD in the overall and severely affected populations. Patients with VAD performed significantly worse on the MDRS Motor Performance subtest, the WAIS-R Picture Arrangement subtest, the WAB Writing subtest, the WAIS-R Object Assembly subtest, and the WAB Block Design subtest. The AD group performed significantly worse on the WAB Repetition subtest, and patients with severe AD performed significantly worse on the Story Recall test. CONCLUSIONS: Patients with VAD performed worse on tests that are influenced by frontal and subcortical mechanisms. Patients with AD performed worse on memory and some language subtests. PMID- 7986179 TI - Control of posture in patients with neurologically asymptomatic HIV infection and patients with beginning HIV-1-related encephalopathy. AB - OBJECTIVE: Stance control measurements (sway velocity, sway area, and postural reflexes) were performed in 36 patients with neurologically asymptomatic human immunodeficiency virus infection (HIV) and in 10 patients with beginning HIV type 1 (HIV-1)-related encephalopathy. All recordings were performed using a movable platform system. OBSERVATIONS: Static posturography and postural reflexes revealed pathologic results in patients with beginning HIV-1-related encephalopathy and in about 25% of patients with nonsymptomatic HIV infection in comparison with age- and sex-matched control subjects. CONCLUSIONS: Postural control is well preserved in early HIV infection; thus, it is not an appropriate measure for detecting subclinical deficits, but disturbances of postural control seem to be one of the first neurological abnormalities in patients with beginning HIV-1-related encephalopathy. PMID- 7986180 TI - Fluctuating Parkinson's disease. Treatment with the long-acting dopamine agonist cabergoline. AB - OBJECTIVE: Assessment of the very long-acting dopamine agonist medication cabergoline in the control of motor fluctuations in Parkinson's disease. DESIGN: Open-label trial (13 weeks). SETTING: Referral centers (Mayo Clinic, Rochester, Minn, and Scottsdale, Ariz). PATIENTS: Volunteer sample of 41 patients with idiopathic Parkinson's disease who were experiencing motor fluctuations while receiving stable doses of carbidopa and levodopa. INTERVENTION: Adjunctive oral cabergoline was incrementally administered once daily with the maintenance dose determined by the clinical response (maximum dose, 5 mg/d). MAIN OUTCOME MEASURES: Standardized serial motor examinations were performed, beginning anywhere from 30 minutes before and continuing to 6 hours after test doses of medications were administered. Scores during adjunctive cabergoline therapy were compared with the prestudy baseline scores during therapy with carbidopa and levodopa without cabergoline. RESULTS: Adjunctive cabergoline therapy significantly improved mean motor scores at the time of each standardized serial examination, from 30 minutes to 6 hours after the administration of test doses of medications. Significant motor score improvement was also measured 24 hours after the last cabergoline dose was administered, suggesting a very long-acting antiparkinsonian effect. Mean dyskinesia scores were slightly but nonsignificantly elevated. Diary card "off-time" was improved by 42%, whereas the levodopa dosage was reduced by 18%. Only three patients dropped out (7% of the total), which contrasts with much higher dropout rates owing to adverse events in previous clinical trials of other antiparkinsonian dopamine agonists. CONCLUSIONS: Cabergoline improved motor control in patients with Parkinson's disease who were experiencing clinical fluctuations. Possible advantages of this medication include an extended clinical response (persisting to 24 hours), tolerability, and ease of use (once per day administration). PMID- 7986181 TI - A brief history of the use of interferons as treatment of multiple sclerosis. AB - Interferons (IFNs) are a family of glycoproteins that are naturally secreted by certain cells in response to viral infection. The naturally occurring IFNs confer protection on other cells, preventing them from becoming infected, a phenomenon referred to as "virus interference" by Isaacs and Lindenmann in the first description of these proteins. In addition to their antiviral properties, the IFNs also have complex immunomodulatory, antiproliferative, and hormonelike activities, which are not completely understood. PMID- 7986182 TI - Clinical experiences from Sweden on the use of subcutaneously administered sumatriptan in migraine and cluster headache. AB - This article reviews, from the practitioner's point of view, more than 1 year of clinical experience of the use of subcutaneously administered sumatriptan succinate in the short-term treatment of migraine and cluster headache with regard to advantages and disadvantages of the drug. In accordance with the results of clinical trials, subcutaneous sumatriptan, also in the practitioner's hands, was found to relieve migraine headaches and all other symptoms associated with migraine in most patients and within a reasonable period. Adverse events, however, are common and were perceived by about 70% of the patients. The most common adverse events were pressure/stiffness in the neck and throat (32%), general tiredness (22%), pressure/tightness over the chest (21%), injection site reactions (16%), and tingling sensations in the head and arms (14%). Headache recurrence within 24 hours is a clinical problem not only for the patient but also for the prescribing physician. About every second (53%) migraineur using subcutaneous sumatriptan reports headache recurrence. Headache recurrence appears to be effectively treated by a second injection. Pending valid information about effects, adverse events, headache recurrence, and how to handle the autoinjector, the compliance and tolerability of subcutaneous sumatriptan appear to be most satisfactory among eligible patients with migraine. PMID- 7986183 TI - Superior check ligament desmotomy for treatment of superficial digital flexor tendonitis in thoroughbred and standardbred horses. AB - Bilateral superior check ligament desmotomy was performed on 31 Thoroughbred and 17 Standardbred horses as the sole method of treatment for superficial digital flexor tendonitis. Horses resumed racing between 6 and 19 months after surgery. Horses that were able to compete in 5 or more races without injury to the tendon again were considered to have had a successful return to racing. Twenty-five Thoroughbreds were suitable for later study and 13 of these (52%) raced on 5 or more occasions. Fifteen Standardbreds were suitable for later study and 10 of these (66%) raced on 5 or more occasions. Within the racing industry it is generally thought that about 20 to 30% of horses with superficial digital flexor tendonitis can return to racing after a prolonged rest. The results of this study suggest that bilateral superior check ligament desmotomy may improve the prognosis for a horse returning to racing after injury to the superficial digital flexor tendon. PMID- 7986184 TI - Immunological detection of cardiac glycosides in plants. AB - Australian native and introduced plants were examined, using digoxin immunoassays, to detect the presence of cross-reacting cardiac glycosides. These compounds were found in 27 species from 20 genera. The assay technique can also be used on serum samples to confirm cardiac glycoside ingestion. PMID- 7986185 TI - Comparison of tiletamine-zolazepam-ketamine and tiletamine-zolazepam-ketamine xylazine anaesthesia in sheep. AB - The anaesthetic effects of intravenous tiletamine-zolazepam 6.6 mg/kg-ketamine 6.6 mg/kg (TK) and tiletamine-zolazepam 6.6 mg/kg-ketamine 6.6 mg/kg-xylazine 0.11 mg/kg (TKX) were evaluated in six wethers. Heart rate, respiration rate, arterial blood pressure, and the electrocardiogram were monitored during anaesthesia. Analgesia was tested by electrical stimulation in the left flank. Atropine (0.03 mg/kg) was given intramuscularly before induction, but after recording of baseline heart rate and respiratory rate. The duration of analgesia was 28.7 +/- 6.9 min with TK and 82.8 +/- 26.6 min with TKX. Heart rate increased significantly within 5 min after TK or TKX administration. Respiratory rate remained unchanged after TK administration, but increased significantly from 5 to 45 min after TKX administration. Arterial blood pressure decreased significantly at 15 min with TK and 30 min with TKX. Sheep remained recumbent for 201 min with TK and 166 min with TKX. All recovered uneventfully. We conclude that either TK or TKX may be used for anaesthetising sheep. PMID- 7986186 TI - The growth of the livestock industries and the veterinary profession in Australia to 1850. PMID- 7986187 TI - Frequency of pancreatic amyloid deposition in cats from south-eastern Queensland. AB - Stereological procedures were used to estimate the amount of amyloid deposition in the pancreatic islets of 83 cats from random sources in south-eastern Queensland. Most had only minor deposits of less than 20% of islet volume (median 9%), but deposits equal to more than 50% of the islet volume were found in 10% of the cats. Amyloid deposition in pancreatic islets was correlated with the age of the cat. Although similar observations have been made previously in cats from the USA, the frequency of amyloid deposition was higher in this population of cats from south-eastern Queensland. PMID- 7986188 TI - Reactions to strangles vaccination. PMID- 7986189 TI - Strain variation in the killing of staphylococci by avian heterophils. PMID- 7986190 TI - Lupin supplements for rams during mating. PMID- 7986191 TI - Isolation of Haemophilus taxon D from pigs in Australia. PMID- 7986192 TI - Severe haemorrhage in Dobermann dogs with von Willebrand's disease and its control during surgery. PMID- 7986193 TI - Rabbit haemorrhagic disease virus: a calicivirus with differences. PMID- 7986194 TI - The prevalence of lice (Bovicola ovis) infested sheep flocks in Western Australia (1987-1993) PMID- 7986195 TI - Transport pathways in the malaria-infected erythrocyte. Their characterization and their use as potential targets for chemotherapy. AB - The intraerythrocytic malarial parasite is involved in an extremely intensive anabolic activity while it resides in its metabolically quiescent host cell. The necessary fast uptake of nutrients and the discharge of waste products are guaranteed by parasite-induced alterations of the constitutive transporters of the host cell and the production of new parallel pathways. The membrane of the host cell thus becomes permeable to phospholipids, purine bases and nucleosides, small non-electrolytes, anions and cations. While the new pathways are quantitatively unimportant for the translocation of a particular solute, classical inhibitors of native transporters can be used to inhibit parasite growth. Several compounds were found to inhibit effectively the new pathways and, consequently, parasite growth. The pathways have also been used to introduce cytotoxic agents. The parasitophorous membrane consists of channels that are highly permeable to small solutes and display no ion selectivity. Transport of some cations and anions across the parasite membrane is rapid and insensitive to classical inhibitors, and in some cases it is mediated by specific antiporters that respond to their respective inhibitors. Macromolecules have been shown to reach the parasitophorous space through a duct contiguous with the host cell membrane, and subsequently to be endocytosed at the parasite membrane. The simultaneous presence of the parasitophorous membrane channels and the duct, however, is incompatible with experimental evidence. No specific inhibitors have been found as yet that would efficiently inhibit transport through the channels or the duct. PMID- 7986197 TI - The reaction of methylglyoxal with aminoguanidine under physiological conditions and prevention of methylglyoxal binding to plasma proteins. AB - Increased formation of methylglyoxal in clinical diabetes mellitus and metabolism by the glyoxalase system has been linked to the development of clinical complications of diabetes: retinopathy, neuropathy and nephropathy. Aminoguanidine has been proposed as a prophylactic agent for preventive therapy of diabetic complications. Methylglyoxal reacted with aminoguanidine under physiological conditions to form two isomeric triazines, 3-amino-5-methyl-1,2,4 triazine and 3-amino-6-methyl-1,2,4-triazine. The mean second order rate constant for the reaction of methylglyoxal with aminoguanidine, kMG.AG = 0.39 +/- 0.06 M-1 sec-1 at pH 7.4 and 37 degrees. Under these conditions, no methylglyoxal bisguanylhydrazone was detected. Aminoguanidine prevented the irreversible modification of human plasma protein by a physiological concentration of methylglyoxal (1 microM); the median inhibitory concentration IC50 value of aminoguanidine was 203 +/- 16 microM (N = 28). The scavenging of methylglyoxal by aminoguanidine may contribute to the beneficial effects of aminoguanidine in the prevention of vascular pathogenesis in diabetes. PMID- 7986196 TI - Differential activation of dibutyryl cAMP-differentiated HL-60 human leukemia cells by chemoattractants. AB - Dibutyryl cAMP-differentiated HL-60 human leukemia cells possess receptors for the chemoattractants N-formyl-L-methionyl-L-leucyl-L-phenylalanine (fMLP), C5a and leukotriene B4 (LTB4). We compared the effects of these chemoattractants in HL-60 membranes and in intact HL-60 cells. fMLP, C5a and LTB4 stimulated GTP hydrolysis and guanosine 5'-O-[3-thio]triphosphate (GTP[gamma S]) binding in HL 60 membranes with similar effectiveness and in a pertussis toxin (PTX)-sensitive manner. They also stimulated photolabeling of the alpha-subunits of the guanine nucleotide-binding proteins (G-proteins), Gi2 and Gi3 with similar effectiveness. Chloride salts of monovalent cations differentially enhanced and inhibited chemoattractant-induced GTP hydrolyses. C5a was less effective than fMLP in enhancing cholera toxin-catalysed ADP-ribosylation of Gi alpha 2 and Gi alpha 3, and LTB4 was ineffective. fMLP was more effective than C5a and LTB4 in stimulating Ca2+ influx in HL-60 cells. C5a- and LTB4-induced rises in cytosolic Ca2+ concentration ([Ca2+]i) were PTX-sensitive, whereas the effect of fMLP was partially PTX-insensitive. LTB4-induced rises in [Ca2+]i were more sensitive towards homologous desensitization than those induced by C5a, and the effect of fMLP was resistant in this regard. C5a was considerably less effective than fMLP in activating superoxide anion formation and azurophilic granule release, and LTB4 was ineffective. Our data suggest that fMLP, C5a and LTB4 effectively activate the G-proteins, Gi2 and Gi3, in HL-60 cells and that fMLP may additionally activate PTX-insensitive G-proteins. fMLP, C5a and LTB4 are full, partial and incomplete secretagogues, respectively, and these differences may be due to differences in homologous receptor desensitization and qualitative Gi protein activation. PMID- 7986198 TI - Comparison of mechanisms responsible for resistance to idarubicin and daunorubicin in multidrug resistant LoVo cell lines. AB - Two human colon carcinoma drug resistant clones (LoVo-IDA-1 and LoVo-IDA-2) were selected by continuous pressure of LoVo parent cell lines to idarubicin (IDA). Both cell sublines exhibited a typical multidrug resistance (MDR) phenotype but, despite IDA selection, the resistance index (RIext) was higher for daunorubicin (DAU) (RIext = 101-112) than for IDA (RIext = 20-23). A similar pattern of cross resistance was also observed in two (DOX) doxorubicin-selected LoVo cell lines (LoVo-DOX-1 and LoVo-DOX-2). All the MDR cell lines exhibited decreased drug accumulation and increased intracellular drug tolerance as evidenced by the greater intracellular amount of drug required to cause a 50% growth inhibition (IC50int) compared to their parent cell line. The differences between DAU and IDA RIext exhibited by MDR cells were a function of intracellular resistance. DAU IC50int was 13.9 and 14.9 times higher in LoVo-IDA-1,2 and 6.4 and 6.2 in LoVo DOX-1,2 cell lines, respectively, than in LoVo-sensitive cells, whereas IDA IC50int was only 3.6 and 3.2 times higher in LoVo-IDA-1,2 and 2.2 and 2.3 in LoVo DOX-1,2 cell lines, respectively. Conversely, variations in IDA accumulation between resistant and sensitive cells were similar to those observed for DAU [the ratios between DAU uptake in sensitive and resistant cells were almost identical (P = NS) to those observed for IDA]. Differences between IDA and DAU intracellular distribution accounted for the relatively higher DAU intracellular resistance. In fact nuclear/cytoplasmic (N/C) DAU fluorescence ratio was higher (P < 0.01) in sensitive (N/C = 3.4 +/- 2.7) than in MDR cells (N/C ranging from 0.31 +/- 0.2 to 0.41 +/- 0.1). In contrast, no significant (P = NS) differences were observed in IDA N/C ratios between sensitive and MDR cells (N/C ranging from 0.16 +/- 0.1 to 0.20 +/- 0.1). In MDR cells, 1-hr VER (10 microM) treatment partially reverted both DAU N/C ratios and intracellular DAU resistance but neither changes in IDA N/C ratios nor variation in intracellular IDA resistance were observed following VER exposure. In conclusion, the greater intracellular drug tolerance that MDR cells show for DAU compared to IDA makes IDA more effective than DAU in MDR cells overexpressing P-glycoprotein (P-gp). PMID- 7986199 TI - Pyrrolidine dithiocarbamate, a potent inhibitor of nuclear factor kappa B (NF kappa B) activation, prevents apoptosis in human promyelocytic leukemia HL-60 cells and thymocytes. AB - We examined the effect of pyrrolidine dithiocarbamate (PDTC), which potently blocks the activation of nuclear factor kappa B (NF-kappa B), on the induction of apoptosis by a variety of agents. Treatment of a human promyelocytic leukemia cell line, HL-60, with 10 micrograms/mL etoposide or 2 microM 1-beta-D arabinofuranosylcytosine induced NF-kappa B activation within 1 hr and subsequently caused apoptosis within 3-4 hr. The simultaneous addition of 50-500 microM PDTC with these agents blocked NF-kappa B activation and completely abrogated both morphologically apoptotic changes and internucleosomal DNA fragmentation for up to 6 hr. However, PDTC failed to inhibit the endonuclease activity contained in the whole cell lysates. The inhibitory effect of PDTC was also observed in etoposide- and dexamethasone-induced apoptosis in human thymocytes at a concentration of 1-10 microM. Since PDTC has both antioxidant and metal-ion chelating activities, we tested the effects of N-acetyl-L-cysteine (NAC) (antioxidant) or o-phenanthroline (OP) (metal-ion chelator) on the induction of apoptosis. Pretreatment of HL-60 cells or thymocytes with 100-500 microM OP for 2 hr, but not 10-60 mM NAC, suppressed subsequent occurrence of apoptosis induced by etoposide. These results suggest that the activation of NF kappa B plays an important role in the apoptotic process of human hematopoietic cells. PMID- 7986200 TI - Role of the CYP2D subfamily in metabolism-dependent covalent binding of propranolol to liver microsomal protein in rats. AB - In vitro covalent binding of a chemically reactive metabolite of propranolol to microsomal macromolecules, which is presumed to cause inhibition of its own metabolism in rats, was diminished in liver microsomes from rats pretreated with propranolol. Covalent binding was suppressed by the addition of an antibody against P450BTL, which is a cytochrome P450 (P450) isozyme belonging to the CYP2D subfamily. SDS-PAGE of microsomal proteins after incubation with [3H]propranolol and NADPH indicated that the binding was non-selective but prominent at the molecular mass of approx. 50 kDa, corresponding to those of the P450 protein. The radioactivity peak was markedly but not completely diminished by the addition of reduced glutathione. In a reconstituted system containing P450BTL, NADPH cytochrome P450 reductase (fp2) and dilauroylphosphatidylcholine, propranolol 4-, 5- and 7-hydroxylase activities decreased time dependently following preincubation with propranolol in the presence of NADPH, indicating time dependent inactivation of P450BTL. The covalent binding of a reactive metabolite of [3H]propranolol to the proteins was also observed in this system. SDS-PAGE showed that among the three proteins in the reconstituted system, fp2 and P450BTL consisting of two polypeptides with molecular masses of 49 and 32 kDa, the binding was specific for a polypeptide corresponding to the P450 isozyme with a molecular mass of 49 kDa. In addition, the ratio of the amount of covalently bound radiolabelled materials to that of P450BTL which was estimated from each impaired propranolol hydroxylase activity under the same reconstitutional conditions was calculated to be approx. 1.0. These findings indicate that propranolol is a mechanism-based inactivator of a cytochrome P450 isozyme(s) belonging to the CYP2D subfamily. PMID- 7986202 TI - Platelet-activating factor (PAF)-induced platelet aggregation. Modulation by plasma adenosine and methylxanthines. AB - This study examined the role of plasma adenosine in the modulation of platelet activating factor (PAF) activity on platelet aggregation and serotonin (5-HT) release in human platelet-rich plasma (PRP). In addition, the effects of methylxanthines (e.g. theophylline and caffeine) were studied on PAF-induced platelet aggregation in PRP isolated from blood samples from healthy subjects. Also, PAF-induced platelet aggregation was examined in PRP samples of patients receiving theophylline treatment. These studies demonstrate that plasma adenosine levels (0.1 to 0.3 microM) play a key role in negative modulation of PAF activity on platelet aggregation and 5-HT release. After depletion of plasma adenosine, the platelet-aggregating activity of PAF was increased greatly (> 10-fold). PAF at concentrations of 0.1 to 12 microM caused no 5-HT release in PRP containing normal amounts of adenosine (blood collected in the presence of 2' deoxycoformycin and dilazep), whereas PAF at 0.1 microM caused 5-HT release (45%) in adenosine-depleted PRP, demonstrating that plasma adenosine is much more inhibitory of 5-HT release than platelet aggregation. The adenosine antagonists theophylline (50 microM), caffeine (50 microM) and a xanthine derivative, 3,7 dimethyl-l-propargylxanthine (DMPX, 10 microM) (a more specific adenosine A2 receptor antagonist), potentiated PAF activity on platelet aggregation in PRP samples containing adenosine. Also, patients receiving theophylline treatments showed significantly greater platelet aggregation induced by PAF in their PRP samples. PAF induced a rapid increase (80% in 15 sec) in intracellular Ca2+ mobilization, which was strongly inhibited by adenosine (IC50, 0.3 microM). Our studies suggest that agents that can increase plasma adenosine levels (e.g. inhibitors of adenosine uptake and adenosine metabolism) or methylxanthines may be useful in altering (inhibiting or enhancing, respectively) PAF actions on platelets and other tissues. PMID- 7986201 TI - Suppression of the humoral immune response by cannabinoids is partially mediated through inhibition of adenylate cyclase by a pertussis toxin-sensitive G-protein coupled mechanism. AB - Cannabinoid compounds, including the major psychoactive component of marihuana, delta 9-tetrahydrocannabinol (delta 9-THC), have been widely established as being inhibitory on a broad array of humoral and cell-mediated immune responses. The presence of cannabinoid receptors has been identified recently on mouse spleen cells, which possess structural and functional characteristics similar to those of the G-protein coupled cannabinoid receptor originally identified in rat brain. These findings, together with those demonstrating that delta 9-THC inhibits adenylate cyclase in splenocytes, strongly suggest that certain aspects of immune inhibition by cannabinoids may be mediated through a cannabinoid receptor associated mechanism. The objective of the present studies was to determine whether inhibition of adenylate cyclase is relevant to mouse spleen cell immune function and, if so, whether this inhibition is mediated through a Gi-protein coupled mechanism as previously described in neuronal tissue. Spleen cell activation by the phorbol ester phorbol-12-myristate-13-acetate (PMA), plus the calcium ionophore ionomycin, produced a rapid but transient increase in cytosolic cAMP, which was inhibited completely by immunosuppressive concentrations of delta 9-THC (22 microM) and the synthetic bicyclic cannabinoid CP-55940 (5.2 microM), which produced no effect on cell viability. Inhibition by cannabinoids of lymphocyte proliferative responses to PMA plus ionomycin and sheep erythrocyte (sRBC) IgM antibody-forming cell (AFC) response, was abrogated completely by low concentrations of dibutyryl-cAMP (10-100 microM). Inhibition of the sRBC AFC response by both delta 9-THC (22 microM) and CP-55940 (5.2 microM) was also abrogated by preincubation of splenocytes for 24 hr with pertussis toxin (0.1-100 ng/mL). Pertussis toxin pretreatment of spleen cells was also found to directly abrogate cannabinoid inhibition of adenylate cyclase, as measured by forskolin stimulated accumulation of intracellular cAMP. These results indicate that inhibition of the sRBC AFC response by cannabinoids is mediated, at least in part, by inhibition of adenylate cyclase through a pertussis toxin-sensitive Gi protein coupled cannabinoid receptor. Additionally, these studies further support the premise that cAMP is an important mediator of lymphocyte activation. PMID- 7986203 TI - Photolysis of sulfiram: a mechanism for its disulfiram-like reaction. AB - Sulfiram, a drug applied topically to treat scabies, produces effects similar to those of disulfiram after subsequent ingestion of ethanol. Disulfiram, used in aversion therapy in the treatment of alcoholism, inhibits hepatic aldehyde dehydrogenase (ALDH) causing an accumulation of acetaldehyde after ethanol ingestion. The increased tissue levels of acetaldehyde cause a spectrum of undesirable side-effects including flushing, nausea, vomiting, and tachycardia, which are referred to as the disulfiram reaction. Previous studies have shown that in vitro sulfiram is a very weak inhibitor of ALDH, but solutions of sulfiram markedly increase in potency with time. In the present study, fresh solutions of sulfiram were exposed to fluorescent room light under ambient conditions and analyzed at timed intervals by HPLC. At least eight products, including disulfiram, were formed in the light-exposed sulfiram solutions, but not in solutions kept in the dark. Structural characterization of two of the photolysis products was obtained by on-line microbore HPLC-mass spectrometry (mu LC-MS) and on-line microbore HPLC-tandem mass spectrometry (mu LC-MS/MS) using continuous flow-liquid secondary ion mass spectrometry (CF-LSIMS) as the primary ionization method. Sulfiram was converted to disulfiram at an initial rate of 0.7%/hr, and the formation of disulfiram correlated with the increase in ALDH inhibition in vitro. The results of this investigation show that while sulfiram is a weak inhibitor of ALDH in vitro, it is readily photoconverted to disulfiram, a very potent inhibitor of ALDH, which may explain the adverse reaction to ethanol after sulfiram therapy. PMID- 7986204 TI - Differential induction of gene expression of catecholamine biosynthetic enzymes and preferential increase in norepinephrine by forskolin. AB - We examined the effect of forskolin, an adenylate cyclase activator, on gene expression and the activities of the three enzymes specific for catecholamine biosynthesis [tyrosine hydroxylase (TH), dopamine beta-hydroxylase (DBH) and phenylethanolamine N-methyltransferase (PNMT)] and on the amounts of available catecholamines in primary cultured bovine adrenomedullary chromaffin cells. The results showed that TH was increased by 4.7 +/- 0.7-fold and 69% in mRNA and activity levels, respectively, compared with the untreated control. DBH was elevated by 3.2 +/- 0.2-fold in mRNA and 45% in activity. The increase in PNMT, on the other hand, was smaller: 1.7 +/- 0.2-fold in mRNA and 13% in activity. This relatively small increase in PNMT was reflected in the catecholamine levels in that the total epinephrine (EPI) was elevated by only 16% while norepinephrine (NE) was elevated by 99%, which caused a shift in the molar ratio of EPI to NE from 7.0 in the untreated control to 4.1 after forskolin treatment. A large portion of the elevated catecholamines was found in the medium, which represented a 10.1-fold increase for NE and a 6.4-fold increase for EPI compared with the control. Interestingly, this caused the remaining intracellular NE and EPI to be only 117 and 66% of the control, respectively. Thus, forskolin caused coordinate up-regulation of gene expression and enzyme activities of the three catecholamine synthesizing enzymes but to different degrees, resulting in a relatively larger increase in NE than in EPI, both of which were released dramatically. This large enhancement of catecholamine release, as well as the dramatic shift in their ratio, implicates an important physiological role for cAMP in the regulation of in vivo sympathetic activities. PMID- 7986205 TI - Inhibition of tumoral cell respiration and growth by nordihydroguaiaretic acid. AB - The effects of nordihydroguaiaretic acid (NDGA), best known as an inhibitor of lipoxygenase activities, on the culture growth, oxygen consumption, ATP level, viability, and redox state of some electron carriers of intact TA3 and 786A ascites tumor cells have been studied. NDGA inhibited the respiration rate of these two tumor cell lines by preventing electron flow through the respiratory chain. Consequently, ATP levels, cell viability and culture growth rates were decreased. NDGA did not noticeably inhibit electron flow through both cytochrome oxidase and ubiquinone-cytochrome b-c1 complex. Also, the presence of NDGA changed to redox state of NAD(P)+ to a more reduced level, and the redox states of ubiquinone, cytochrome b and cytochromes c + c1 changed to a more oxidized level. These observations suggest that the electron transport in the tumor mitochondria was inhibited by NDGA at the NADH-dehydrogenase-ubiquinone level (energy-conserving site 1). As a consequence, mitochondrial ATP synthesis would be interrupted. This event could be related to the cytotoxic effect of NDGA. PMID- 7986206 TI - Intrinsic cellular resistance to oxazaphosphorines exhibited by a human colon carcinoma cell line expressing relatively large amounts of a class-3 aldehyde dehydrogenase. AB - A cultured human colon carcinoma cell line, viz. colon C, exhibiting intrinsic cellular resistance to mafosfamide mediated by relatively elevated levels of a cytosolic class-3 aldehyde dehydrogenase was identified. Colon C cells were found to be much less sensitive/more resistant (about 10-fold as judged by LC90 values) to mafosfamide than were two other cultured human colon carcinoma cell lines, viz. RCA and HCT 116b, and, as compared to the barely detectable aldehyde dehydrogenase activity (NADP-dependent enzyme-catalyzed oxidation of benzaldehyde to benzoic acid) in RCA and HCT 116b cells, that in colon C cells was about 200 fold greater. The three cell lines were equisensitive to phosphoramide mustard. Aldehyde dehydrogenase activity was confined to the cytosol in colon C cells (as well as in the other two cell lines) and, on the basis of its physical, immunological and catalytic characteristics, the operative enzyme was judged to be a Type-1 ALDH-3 identical to the Type-1 ALDH-3 expressed in methylcholanthrene treated human breast adenocarcinoma MCF-7/0 cells and very nearly identical to the Type-1 ALDH-3 expressed in human normal stomach mucosa. Class-1 and class-2 aldehyde dehydrogenases were not found in these cells. The relative insensitivity to mafosfamide on the part of colon C cells was not observed when exposure to mafosfamide was in the presence of benzaldehyde or 4-(diethylamino)benzaldehyde, each a relatively good substrate for ALDH-3, whereas it was retained when exposure to mafosfamide was in the presence of acetaldehyde, a relatively poor substrate for this enzyme. Sensitivity to mafosfamide on the part of HCT 116b and RCA cells, and to phosphoramide mustard on the part of all three cell lines, was unaffected when drug exposure was in the presence of any of the three aldehydes. Together with earlier reports from our laboratory, these observations demonstrate that intrinsic, as well as stable and transient acquired, resistance to oxazaphosphorines, such as mafosfamide and cyclophosphamide, can be mediated by relatively increased levels of cytosolic class-3 aldehyde dehydrogenases. PMID- 7986207 TI - Induction, suppression and inhibition of multiple hepatic cytochrome P450 isozymes in the male rat and bobwhite quail (Colinus virginianus) by ergosterol biosynthesis inhibiting fungicides (EBIFs). AB - Ergosterol biosynthesis inhibiting fungicides (EBIFs) have complex effects on the hepatic microsomal monooxygenase systems of vertebrate species, having been described as mixed inducers and inhibitors of cytochrome P450. In the current study, we examined the effects of two EBIFs in clinical use, clotrimazole and ketoconazole, and two agricultural EBIFs, propiconazole and vinclozolin, on hepatic monooxygenase activities and P450 apoprotein expression in the male Sprague-Dawley rat and the male bobwhite quail. EBIFs produced Type II binding spectra with hepatic microsomes from both species and were effective inhibitors of methoxyresorufin O-demethylase, an activity selective for P450 isozymes in gene family 1. However, the EBIFs varied widely in their effectiveness as inducers of P450 isozymes in gene families 1, 2, 3 and 4, both within the same species and between species. In the rat, clotrimazole was the most effective inducer, increasing expression of CYP 3A isozymes over 450-fold, CYP 2B1/2 30 fold and CYP 1A1/2 12-fold and suppressing expression of CYP 2C11 nearly 70%. By contrast, in the quail, clotrimazole was the least effective inducer. In quail, vinclozolin and propiconazole elevated total P450 content 10- and 7-fold, respectively. The induction response also appeared to be mixed, but in this case consisted of a 5-fold induction of P450s in gene family 1A, a 3-fold induction of P450s in gene family 3A and 4A, and induction of protein(s) from gene family 2, cross-reactive with antisera against rat CYP 2C11 and CYP 2A1. A protein that was cross-reactive with antibodies raised against rat CYP 2B1 was decreased with EBIF treatment. In conclusion, EBIFs have complex patterns of induction, suppression and inhibition of cytochrome P450 isozymes in both mammals and birds, which vary according to both the fungicide and the species. PMID- 7986208 TI - Measurement of superoxide anion production using maximal rate of cytochrome (III) C reduction in phorbol ester stimulated neutrophils, immobilised to microtiter plates. AB - In the present investigation, a method of studying the maximal rate of superoxide anion (O2.-) production in immobilised human neutrophils using a microtiter plate technique has been developed. The rate of O2.- production was determined from the rate of reduction of cytochrome (III) C, studied as the increase in absorbance at 550 nm. The protein kinase C activator, phorbol 12-myristate 13-acetate, was used to stimulate O2.- production. Neutrophils were evenly immobilised as a monolayer to microtiter culture plates to provide a reproducible exposure to the medium. Phorbol ester stimulated O2.- production was inhibited by staurosporine, a well known inhibitor of protein kinase C, and by diphenylene iodonium, a potent NADPH oxidase inhibitor, with IC50-values in this assay of 20 and 220 nm, respectively. The extracellularly produced O2.- was removed by superoxide dismutase with a half maximal effect of 0.6 microgram/mL. The maximal production rate of O2.- could therefore be estimated by addition of 20 micrograms/mL superoxide dismutase. Several antioxidants, including butylated hydroxytoluene, nordihydroguairetic acid, probucol and alpha-tocopherol, were studied and showed neither an effect on O2.- production nor a scavenging effect. This new method was highly reproducible, and the continuous measurement of O2.- production was very useful for validating the effect of inhibitors. The developed microtiter technique using immobilised cells has a large capacity and allows different compounds to be tested under comparable conditions, since they are exposed to the cells in a similar way. This is also the first test model which describes O2.- production as the maximal rate of cytochrome (III) C reduction. PMID- 7986209 TI - Aminotriazole is a potent inhibitor of alpha-oxidation of 3-methyl-substituted fatty acids in rat liver. AB - The production of CO2 and formate in isolated rat hepatocytes incubated in the presence of 3-methyl[1-14C]margaric acid was investigated. Production rates of formate were approximately 4-fold lower than those of CO2. Aminotriazole (3-amino 1, 2, 4-triazole), an irreversible inhibitor of catalase, potently suppressed alpha-oxidation of 3-methylmargaric acid, whereas beta-oxidation of palmitate, 2 methylpalmitate and trihydroxycoprostanic acid and conversion of exogenously added formate to CO2 were not or only slightly affected. This shows that aminotriazole is not only an inhibitor of catalase, but also of alpha-oxidation of 3-methyl-substituted fatty acids. PMID- 7986210 TI - The influence of picolines on glutathione transferase activity and subunit composition in human liver derived Hep G2 cells. AB - Hep G2 cells, an established cell line derived from a human hepatoma, have retained a number of hepatocytic phase I and II reactions. The influence of picolines (2-, 3- and 4-methylpyridine), related compounds and some classical enzyme inducers on specific glutathione transferase (GST) activity and its subunit composition in Hep G2 cells was investigated. Increased GST activity was observed for rifamycin, phenobarbital, pyrazine and the picolines, of which the 4 isomer was the strongest inducer. The GST subunits were analysed by HPLC. GSTP1, GSTM1a, GSTA1 and GSTA2 were present in control Hep G2 cells. GSTM1a disappeared or was strongly reduced under the influence of the test chemicals. All GST increases were due to augmented GSTA1 expression. Thus, picolines stimulate GST activity in Hep G2 cells by influencing the class alpha GSTA1. PMID- 7986211 TI - Panaxynol, a polyacetylene compound isolated from oriental medicines, inhibits mammalian lipoxygenases. AB - Panaxynol is a polyacetylene compound isolated from commonly used oriental medicines, and its effects on various cyclooxygenases and lipoxygenases were investigated. The compound had only a marginal effect on cyclooxygenase activities (IC50 values >> 100 microM), but inhibited lipoxygenases; 5 lipoxygenase (IC50, 2 microM), two isoforms of 12-lipoxygenase (leukocyte-type, 1 microM; platelet-type, 67 microM) and 15-lipoxygenase (4 microM). Thus, panaxynol inhibited leukocyte-type 12-lipoxygenase much more effectively than platelet-type 12-lipoxygenase. Falcarindiol, an analogue of panaxynol, inhibited these lipoxygenases with higher IC50 values than panaxynol. These compounds could provide a clue to develop a selective inhibitor of one isoform of 12 lipoxygenase. PMID- 7986212 TI - Muscarinic receptor-mediated calcium efflux from cultured bovine adrenal chromaffin cells. AB - The effect of stimulation of the muscarinic receptor on Ca2+ mobilization in cultured bovine adrenal chromaffin cells was examined. Acetylcholine (ACh) increased the uptake of 45Ca2+ and [Ca2+]i whose levels decreased with time after reaching peaks. It also enhanced the efflux of 45Ca2+ from the cells. Its effect was inhibited by the specific muscarinic receptor antagonist atropine (Atr), but not by the nicotinic receptor antagonist hexamethonium (C6). The increase in muscarine (Mus)-stimulated 45Ca2+ efflux was reduced concentration-dependently by deprivation of extracellular Na+. These results suggest that muscarinic stimulation of the ACh receptor stimulates Na+/Ca2+ exchange in cultured bovine adrenal chromaffin cells. PMID- 7986213 TI - Kinetic analysis of the interaction between the diphosphate of (S)-1-(3-hydroxy-2 phosphonylmethoxypropyl)cytosine, ddCTP, AZTTP, and FIAUTP with human DNA polymerases beta and gamma. AB - The inhibitory effects of the diphosphate of (S)-1-(3-hydroxy-2-phosphonylmethoxy propyl)cytosine (HPMPCpp) toward human DNA polymerases beta and gamma were studied. The Ki values of HPMPCpp were compared with the Ki values of the triphosphates of 3'-azidothymidine (AZTTP), 2',3'-dideoxycytidine (ddCTP) and 5 iodo-2'-fluoroarabinosyluridine (FIAUTP). The Ki values toward DNA polymerase beta in increasing order were 1.32, 1.43, 140, and 520 microM for ddCTP, FIAUTP, AZTTP and HPMPCpp, respectively. The Ki values toward DNA polymerase gamma in increasing order were 0.034, 0.031, 18.3 and 299 microM for ddCTP, FIAUTP, AZTTP and HPMPCpp, respectively. Therefore, HPMPC would be expected to have less inhibitory effects on DNA repair (DNA polymerase beta) and mitochondrial DNA synthesis (DNA polymerase gamma) than ddC, FIAU or AZT. PMID- 7986214 TI - In vivo evidence for ATP-dependent and P-glycoprotein-mediated transport of cyclosporin A at the blood-brain barrier. AB - To evaluate the significance of P-glycoprotein (P-gp)-mediated active efflux on the blood-brain barrier (BBB) permeability of cyclosporin A (CsA) in vivo, we investigated the effects of ATP depletion in the brain and of a multidrug resistant (MDR) reversing agent on the transport of CsA across the BBB. Using transient brain ischemia obtained by 4-vessel occlusion of vertebral and common carotid arteries in rats to deplete ATP content in the brain, the estimated permeability surface area product (PS) value of [3H]CsA was increased 2.7-fold compared with that in normal rats, whereas the PS value of [14C]sucrose was not altered. Additionally, when quinidine hydrochloride (QND) was infused into the brain through a microdialysis probe implanted in the rat hippocampus, the extravascular extraction of CsA was increased to approximately 2.5-fold of the control, whereas no difference in the extravascular extraction between control and normal rats having no implanted dialysis probe was observed. Furthermore, the efflux rate from brain to blood of CsA was decreased remarkably to 5% of control at steady-state by co-administration of CsA with QND directly into the brain through the dialysis probe. The ATP-dependent and QND-sensitive efflux of CsA from the brain strongly indicates that P-gp in the brain capillary endothelial cells functions as an efflux pump under the physiological state, and that P-gp mediated efflux of CsA is a major mechanism of the restricted transfer from blood into the brain. PMID- 7986215 TI - Angiotensin II binding activity in cultured porcine arterial endothelial cells. AB - Angiotensin II (A II) binding activity was detected in the particulate fraction (100,000 g, 60 min precipitate) of cultured porcine aortic endothelial cells. Scatchard analysis of the binding activity indicated a single class of binding sites with a dissociation constant (Kd) of 1.1 nM and a total binding capacity (Bmax) of 125 fmol/mg protein. The binding of [125I]A II was inhibited by excess unlabelled A II, A II analogues ([Sar1, Ile8]A II and [Sar1, Ala8]A II), A I (angiotensin I) and A III (angiotensin III), but not by bradykinin. Type specific A II receptor antagonists, losartan (type 1 angiotensin II receptor) and PD123319 (type 2 angiotensin II receptor), did not inhibit the binding. These results suggest that the A II specific binding protein(s) or receptor(s) is present in arterial endothelial cells, and that it is different from typical type 1 and type 2 angiotensin II receptors. PMID- 7986217 TI - Relationship between alpha 1-antitrypsin inactivation and tumor necrosis factor alpha concentration in the synovial fluid of patients with rheumatoid arthritis. AB - OBJECTIVE: To examine the relationship between alpha 1-antitrypsin (alpha 1AT) specific activity and tumor necrosis factor alpha (TNF alpha) concentration in synovial fluid from 48 patients with rheumatoid arthritis. METHODS: The specific activity of alpha 1AT was calculated from the measurement of alpha 1AT concentration (by rocket immunoelectrophoresis) and elastase inhibitory capacity. TNF alpha was detected by enzyme-linked immunosorbent assay. RESULTS: TNF alpha concentrations correlated with the extent of alpha 1AT inactivation. CONCLUSION: Our findings are consistent with a role of elastase in TNF alpha release within the inflamed joint. PMID- 7986216 TI - Interleukin-4 inhibits bone resorption through an effect on osteoclasts and proinflammatory cytokines in an ex vivo model of bone resorption in rheumatoid arthritis. AB - OBJECTIVE: To assess local bone resorption in the context of rheumatoid synovitis and its modulation by interleukin-4 (IL-4). METHODS: We developed an ex vivo model of bone resorption using juxtaarticular samples of bone obtained during joint surgery. We studied the histomorphometric parameters of bone resorption and the regulation of the production of IL-6, leukemia inhibitory factor (LIF), and the collagen cross-link pyridinoline, which is released during bone resorption in vivo. RESULTS: This was a sensitive and dynamic model of bone resorption. The bone samples produced high levels of pyridinoline and as much cytokine as synovium pieces obtained from the same joint. IL-4 induced a 70% reduction of IL 6 and LIF production by bone pieces and reduced pyridinoline levels. Histomorphometric studies performed on bone samples indicated a 35% increase in the mean total bone area after 7 days of treatment with IL-4. More importantly, with IL-4, osteoclasts were not detectable in the bone sections. CONCLUSION: The inhibitory effect of IL-4 on bone resorption extends our knowledge of its antiinflammatory properties and suggests that the inflammatory cytokine imbalance in rheumatoid synovium also contributes to defects in bone resorption in RA. PMID- 7986218 TI - Doxycycline disrupts chondrocyte differentiation and inhibits cartilage matrix degradation. AB - OBJECTIVE: The effects of doxycycline were tested in an in vitro system in which the cartilages of embryonic avian tibias are completely degraded. METHODS: Tibias were cultured with 5, 20, or 40 microgram/ml doxycycline. Control tibias were cultured without doxycycline. Conditioned media and tissue sections were examined for enzyme activity and matrix loss. RESULTS: Cartilages were not resorbed in the presence of doxycycline, whereas control cartilages were completely degraded. Collagen degradation was reduced in association with treatment with doxycycline at all doses studied. Higher concentrations of doxycycline reduced collagenase and gelatinase activity and prevented proteoglycan loss, cell death, and deposition of type X collagen in the cartilage matrix; in addition, treatment with doxycycline at higher concentrations caused increases in the length of the hypertrophic region. CONCLUSION: The effects of doxycycline extend beyond inhibition of the proteolytic enzymes by stimulating cartilage growth and disrupting the terminal differentiation of chondrocytes. PMID- 7986219 TI - Granzyme-positive cytotoxic cells are specifically increased in early rheumatoid synovial tissue. AB - OBJECTIVE: To define the expression and the phenotype of granzyme (Gran) A and B positive cytotoxic cells in synovial tissue (ST) from patients with rheumatoid arthritis (RA) with respect to disease duration and activity. METHODS: Using antibodies against GranA and GranB, which serve as markers of activated natural killer (NK) cells and cytotoxic T lymphocytes, ST sections from 10 patients with early RA, 10 patients with longstanding RA, and 10 patients with osteoarthritis were examined. The phenotype of Gran+ cells was determined with double-labeling techniques. RESULTS: Gran+ cells, the majority of which were NK cells, were found in ST from patients in all groups. Several of these cells did not express the surface markers CD16, CD56, and CD57. The highest ST expression of GranB was found in patients with early RA. In RA patients, there was a positive correlation of GranB expression with serum levels of acute-phase reactants, but not with histologic scores for inflammation. CONCLUSION: Gran+ cells are mainly NK cells, a substantial proportion of which do not express conventional NK cell surface markers. GranB expression is specifically increased in the synovial tissues of patients with RA of short duration. PMID- 7986220 TI - Elevated serum levels of interleukin-1 receptor antagonist in polymyositis/dermatomyositis. A biologic marker of disease activity with a possible role in the lack of acute-phase protein response. AB - OBJECTIVE: To determine whether the lack of acute-phase protein (APP) response in numerous patients with polymyositis/dermatomyositis (PM/DM) is related to an imbalance between cytokines and cytokine inhibitors. METHODS: Levels of C reactive protein (CRP), interleukin-1 beta (IL-1 beta), tumor necrosis factor alpha (TNF alpha), IL-6, IL-1 receptor antagonist (IL-1ra), TNF soluble receptor 55 kd (sTNFR 55 kd), and sTNFR 75 kd were tested in the serum of 15 patients with PM/DM, 14 patients with spondylarthropathies (SPA), and 12 healthy blood donors. Serum IL-1 beta, TNF alpha, IL-6, IL-1ra, sTNFR were measured by specific immunoassays. RESULTS: Serum levels of CRP were lower in PM/DM patients than in SPA patients. Normal or slightly elevated CRP values were found in 10 of the 15 PM/DM patients, 7 of whom had active myositis. Serum IL-6 levels were significantly higher in SPA patients than in PM/DM patients, whereas serum IL-1ra and sTNFR levels were significantly higher in PM/DM than in SPA patients. IL-1ra levels were particularly elevated in patients with active myositis and decreased in response to treatment. CONCLUSION: These differences in cytokine levels, particularly IL-1ra, between PM/DM and SPA patients are indicative of distinct pathogenic mechanisms. High levels of IL-1ra may account for the weak APP response in some PM/DM patients. Our results suggest that measurement of IL-1ra, together with clinical examination, may provide useful information for the followup of PM/DM patients. PMID- 7986221 TI - Combined treatment with terbutaline and aminophylline inhibits experimental amyloidosis in mice. AB - OBJECTIVE: To investigate the effects of drugs known to elevate adenosine 3':5' cyclic monophosphate (cAMP) on experimental amyloidosis. METHODS: A beta 2 agonist, terbutaline, and a phosphodiesterase inhibitor, aminophylline, were administered in combination in a mouse model of amyloidosis induced by inflammatory stimulation with silver nitrate. Amyloidosis was quantitated by radioimmunoassay for splenic amyloid A (AA) protein. RESULTS: At the doses selected, aminophylline/terbutaline inhibited splenic amyloid deposition more potently than did colchicine, a known inhibitor of amyloidosis. CONCLUSION: Drugs known to elevate cAMP inhibit experimental mouse AA amyloidosis. PMID- 7986222 TI - Measurement of health status in children with juvenile rheumatoid arthritis. AB - OBJECTIVE: To develop and validate a self- or parent-administered instrument for measuring functional status in children with juvenile rheumatoid arthritis (JRA). METHODS: We adapted the Stanford Health Assessment Questionnaire (HAQ) for use in children ages 1-19 years, by adding several new questions, such that for each functional area, there was at least 1 question relevant to children of all ages. The face validity of the instrument was evaluated by a group of 20 health professionals and parents of 22 healthy children. The questionnaire was then administered to parents of 72 JRA patients (mean age 9.1 years, onset type systemic in 16, polyarticular in 21, pauciarticular in 35). RESULTS: The instrument showed excellent internal reliability (Cronbach's alpha = 0.94), with a mean inter-item correlation of 0.6. The convergent validity was demonstrated by strong correlations of the Disability Index (average of scores on all functional areas) with Steinbrocker functional class (Kendall's tau b = 0.77, P < 0.0001), number of involved joints (Kendall's tau b = 0.67, P < 0.0001), and morning stiffness (Kendall's tau b = 0.54, P < 0.0001). Spearman's correlation coefficient between Disability Index scores from questionnaires administered to parents and those from questionnaires administered to older children (> 8 years) was 0.84 (n = 29; P < 0.001), showing that parents can accurately report for their children. The test-retest reliability, studied at a 2-week interval, revealed virtually identical Disability Index scores measured on the 2 occasions (0.96 versus 0.96; P > 0.9 by paired t-test; Spearman's correlation coefficient = 0.8, P < 0.002). CONCLUSION: The Childhood HAQ, which takes less than 10 minutes to complete, is a valid, reliable, and sensitive instrument for measuring functional status in children with JRA. PMID- 7986223 TI - Methotrexate concentrations in synovial membrane and trabecular and cortical bone in rheumatoid arthritis patients. AB - OBJECTIVE: To determine methotrexate (MTX) concentrations in the synovial membrane (SM) and cortical and trabecular bone of rheumatoid arthritis (RA) patients. METHODS: Ten RA patients (9 women, 1 man; mean +/- SD age 49.2 +/- 10.6, mean disease duration 13.2 +/- 9.9 years) undergoing surgical procedures for rheumatoid articular lesions participated in this study. Mean +/- SD MTX treatment duration was 26.4 +/- 21.3 months. The day preceding surgery, 10 mg of MTX was administered intramuscularly. During surgery, a mean +/- SD of 19.7 +/- 2.6 hours after MTX administration, SM, bone fragments, and blood were collected simultaneously. MTX was assayed by fluorescence polarization immunoassay in plasma and tissues. RESULTS: The mean +/- SD plasma concentration was 0.0252 +/- 0.01 nmoles/ml at the time of tissue sampling. The mean MTX concentration in SM was 0.285 +/- 0.159 nmoles/gm. The mean MTX concentrations in trabecular and cortical bone were 0.292 +/- 0.164 and 0.286 +/- 0.126 nmoles/gm, respectively. CONCLUSION: After intramuscular administration, high MTX concentrations are found in SM and cortical and trabecular bone of RA patients. PMID- 7986224 TI - Serum levels of collagenase, stromelysin-1, and TIMP-1. Age- and sex-related differences in normal subjects and relationship to the extent of joint involvement and serum levels of antigenic keratan sulfate in patients with osteoarthritis. AB - OBJECTIVE: To measure serum levels of collagenase (MMP-1), stromelysin-1 (MMP-3), and tissue inhibitor of matrix metalloproteinases-1 (TIMP-1) in normal subjects and in patients with osteoarthritis (OA), and to assess how these correlate with biochemical and clinical indicators of disease activity in OA. METHODS: Specific immunoassays were used to measure MMPs, TIMP-1, and antigenic keratan sulfate (KS). The total area of cartilage affected by the disease was measured (expressed as an articular index). RESULTS: In the normal population (n = 118), the serum concentration of MMP-3, but not of MMP-1 or TIMP-1, increased with age and was approximately 2 times higher in males than in females. In the OA patients (n = 33), the serum levels of MMP-3, but not of MMP-1 or TIMP-1, were significantly elevated and correlated strongly with the articular index but poorly with objective and subjective functional capacity scores as well as with serum levels of antigenic KS and systemic parameters of inflammation. CONCLUSION: These findings illustrate the importance of matching patients and normal controls for age and sex in further studies of MMP-3 and are consistent with the hypothesis that MMP-3 might play an important role in the degradation of joint cartilage in OA. Further, serum levels of MMP-3 may prove useful for monitoring therapy for OA. PMID- 7986225 TI - Treatment-free remission in severe systemic lupus erythematosus following synchronization of plasmapheresis with subsequent pulse cyclophosphamide. AB - OBJECTIVE: To investigate the effect of an intensified treatment protocol synchronizing plasmapheresis with subsequent pulse cyclophosphamide for severe systemic lupus erythematosus (SLE). METHODS: A protocol of plasmapheresis (3 x 60 ml/kg) and subsequent high-dose pulse cyclophosphamide (36 mg/kg) followed by 6 months of peroral immunosuppression was used to treat 14 patients with severe SLE. RESULTS: Rapid improvement was achieved in all patients. Immunosuppressants, including corticosteroids, were withdrawn at month 6 in 12 patients. Eight patients continued without treatment for a mean observation period of 5.6 years (46-91 months). CONCLUSION: The results demonstrate that treatment-free clinical remission can be achieved in some patients with severe SLE. PMID- 7986226 TI - Antibodies to histone (H2A-H2B)-DNA complexes in the absence of antibodies to double-stranded DNA or to (H2A-H2B) complexes are more sensitive and specific for scleroderma-related disorders than for lupus. AB - OBJECTIVE: To assess the role of antibodies to histones H2A, H2B, and anti-double stranded DNA which form (H2A-H2B)-DNA complexes in patients with scleroderma related disorders. METHODS: Antihistone antibodies were measured, by enzyme immunoassay, in 26 patients with scleroderma-related disorders, 100 patients with systemic lupus erythematosus (SLE), and 24 patients with rheumatoid arthritis. RESULTS: Antibodies to histone (H2A-H2B)-DNA complex were more commonly seen in patients with scleroderma-related disorders than in those with SLE (P < 0.0001). CONCLUSION: Scleroderma-related disorders should be included among conditions in which various types of antihistone antibodies are produced. A hypothesis to account for this finding is discussed. PMID- 7986227 TI - Outcome of polyarteritis nodosa and Churg-Strauss syndrome. An analysis of twenty five patients. AB - OBJECTIVE: To compare outcome in patients with polyarteritis nodosa (PAN) and patients with Churg-Strauss syndrome (CSS) followed up at a single center. METHODS: A retrospective data review of 13 patients with PAN and 12 patients with CSS who were followed up at a vasculitis clinic. Outcome measures included a global damage index, disability and pain dimensions of the Health Assessment Questionnaire, and mortality rate. RESULTS: Compared with patients with CSS, patients with PAN had a significantly higher mean damage index score (5.15 versus 2.42; P = 0.011), a higher disability score (1.09 versus 0.16; P = 0.007), and a higher pain score (1.04 versus 0.01; P = 0.017). Patients with PAN had more relapses (relative risk = 5.07; P < 0.000) and a higher mortality rate (31%) compared with patients with CSS (8%). CONCLUSION: PAN and CSS differ in their morbidity and mortality; therefore, they should be considered as distinct clinical entities. PMID- 7986230 TI - Arthritis and autoimmunity. The Fifteenth Sigrid Juselius International Symposium. PMID- 7986229 TI - Painful acral purpuric nodules. PMID- 7986228 TI - Colchicine treatment of AA amyloidosis of familial Mediterranean fever. An analysis of factors affecting outcome. AB - OBJECTIVE: To elucidate factors possibly influencing the outcome of colchicine therapy in patients with amyloidosis of familial Mediterranean fever (FMF). METHODS: Retrospective analysis of data abstracted from the charts of all 68 FMF patients with amyloidosis who presented during the study period (1974-1992) with proteinuria (> or = 0.5 gm/24 hours) and creatinine values < or = 2.5 mg/dl, received colchicine, and were followed up for > or = 5 years. RESULTS: At the end of the study period, kidney disease had worsened in 31 patients and remained stable in 22. Proteinuria had regressed in 15 patients. Deterioration was related to initial serum creatinine values > or = 1.5 mg/dl (P < 0.01) and to mean colchicine dosage < or = 1.5 mg/day (P < 0.001). The 3 groups were comparable in terms of initial urinary protein levels, duration of proteinuria, presence of hypertension, occurrence of febrile attacks, sex distribution, and proportion of non-compliant patients. CONCLUSION: The therapeutic dosage of colchicine for amyloidosis of FMF is > 1.5 mg/day. This dosage is effective only in patients with initial serum creatinine levels < 1.5 mg/dl. PMID- 7986231 TI - Cushing's disease-induced remission of severe rheumatoid arthritis. PMID- 7986232 TI - Can an earthquake cause flares of rheumatoid arthritis or lupus nephritis? PMID- 7986233 TI - Suggested guidelines for monitoring liver toxicity in rheumatoid arthritis patients treated with methotrexate: comment on the article by Kremer et al. PMID- 7986234 TI - Effects of training and experience on rheumatology reimbursement: comment on the article by Mazzuca and Brandt. PMID- 7986235 TI - Collagenase and stromelysin expression in rheumatoid synovium and cartilage: comment on the article by Wolfe et al. PMID- 7986236 TI - [Evidence for a therapeutic effect of Ginkgo biloba special extract. Meta analysis of 11 clinical studies in patients with cerebrovascular insufficiency in old age]. AB - Eleven controlled clinical trials were evaluated in a meta-analysis in order to proof the effectiveness of the ginkgo biloba special extract LI 1370 (Kaveri forte). All included studies were placebo controlled randomized double blind studies, using in most of the cases a daily dosage of 150 mg extract. The requirements for the quality of the studies were the basic criteria for the performance of clinical drug tests analysed from the biometrical scope. The analysis of the individual studies revealed that three studies had to be excluded from the meta-analysis according to methodological or objective reasons. In two further studies the evaluation of the physician or the patients was missing, therefore the studies could not be used for the analysis of the "global effectiveness". All other studies were comparable with regard to diagnoses, inclusion and exclusion criteria as well as methodology. Therefore a statistical meta-analysis could be performed for them, analysing the parameters "single symptoms", total score of clinical symptoms and "global effectiveness". For all analyzed single symptoms significant differences could be concluded, indicating the superiority of ginkgo biloba in comparison to placebo. The analysis of the total score of clinical symptoms from all relevant studies indicated that 7 studies confirmed the effectiveness (Ginkgo biloba being better compared to placebo) while only one study was inconclusive (the medications were not different). This relation confirms the therapeutical effectiveness of ginkgo biloba regarding the clinical symptom complex. Finally the parameter "global effectiveness" was evaluated.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7986237 TI - Uncoupling of G-protein mediated fluoride contractions of vascular smooth muscle by pHi perturbations. AB - In the presence of extracellular Ca2+ (Cao), isolated preparations of rabbit aortas (RA) and epicardial porcine coronary arteries (PCA) contracted dose dependently to the cumulative addition of NaF (2.5-12 mmol/l); the EC50 values were resp. 6.87 +/- 0.25 (n = 6) and 6.35 +/- 0.42 (n = 11) mmol/l. In Cao-free EGTA-containing solution, the vessel preparations were also contracted by NaF in the same concentration range; however, the maximum effect was only about 20-35% of the fluoride-induced contractions in Ca(2+)-containing solutions. Contractions induced in PCA by 10 mmol/l NaF in the presence and absence of Cao were unaffected by pretreatment with 0.5 mmol/l deferoxamine mesylate. These specific fluoride effects, not mimicked by other halogenides, seem to be only partly mediated by activation of G-protein; they were inhibited in 1.5 mmol/l Cao by verapamil and sodium nitroprusside (NaNP), in Ca(2+)-free solution only by NaNP. Slow developing and sustained contractions, similar in time course and amplitude to fluoride contractions, were induced in RA byy phorbol 12,13-dibutyrate. Contractions induced by depolarization (50 mmol/l KCl) and by NaF were additive, suggesting distinct mechanisms of action; NaF (2.5 and 10 mmol/l) shifted cumulative concentration-response (CCR) curves for PCA contractions to KCl (20 100 mmol/l) to the left and also potentiated the maximum response.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7986238 TI - Biotransformation of the organic nitrate trans-N-(4-nitroxycyclohexyl)acetamide in dogs. AB - The biotransformation of BM 12.1307 (trans-N-(4-nitroxycyclohexyl)acetamide, CAS 137291-91-3) in the dog was examined after oral and intravenous administration. For that purpose, the organic nitrate was synthesized as radioactive [14C]- and as [13C]-labeled compounds. The defined isotopic mixture was administered to the dogs. Within the examined period of 168 h, the elimination of BM 12.1307 and its metabolites via urine and feces amounted to 76.5% after oral application, and to 80.7% of the applied dose after intravenous application. The major amount of radioactivity was eliminated via urine (69.4% and 73.6% of the dose, respectively), whereas the fecal elimination was found to be negligible. Investigations of the urinary samples showed that the drug is metabolized to a high percentage trans-N-(4-Hydroxycyclohexyl) acetamide is the main metabolite; 73% of the radioactive compounds (after p.o.-administration and 69% after intravenous application could be identified as the alcohol of BM 12.1307; the amounts of the drug totalled 9% and 13%, respectively. The quantitative determination of BM 12.1307 in urine and plasma was performed by gas chromatography; the amount of the main metabolite excreted in urine was determined by high-pressure liquid chromatography. Trans-N-(4-hydroxycyclohexyl) acetamide, N-(4-oxocyclohexyl)acetamide, and 3-acetamido-7-oxa-bicyclo [4.1.0]heptane were formed as metabolites. For the identification and characterization of the possible metabolic structures, these compounds were synthesized and used in comparison with the detected drugs. PMID- 7986239 TI - Synthesis and characterization of some novel substituted benzenesulphonamides of potential hypoglycemic activity. AB - Two series of substituted benzenesulphonamides (Va-e and VIa-e) have been synthesized from 4-methoxycarbonyl-1-[p (acetylamino)benzenesulphonylimino]pyridini um ylide (II) with a view to investigate their pharmacological activity. The structure of the synthesized products was inferred from elemental and spectral data. The hypoglycemic effect, antimicrobial activity and toxicity of the possible chemotherapeutic agents were evaluated. Six of these products were effective, when administered at an oral dose of 100 mg/kg b. wt., inducing marked reduction in blood glucose level. PMID- 7986240 TI - Sorbitol-accumulating pyrimidine derivatives. AB - The novel compounds SDI 157 (2-methyl-4(4-N,N-dimethylaminosulfonyl-1 piperazino)pyrimid ine, CAS 131816-54-1) and SDI 158 (2-hydroxymethyl-4-(4-N,N dimethylaminosulfonyl-1- piperazino) pyrimidine, CAS 140687-51-0) have been found to be inhibitors of sorbitol dehydrogenase. In normal and diabetic animals both compounds induced a dose-dependent increase of tissue sorbitol, especially in the peripheral nerve, without alteration of the blood glucose. In contrast to SDI 158, SDI 157 does not act in vitro. However, in the isolated perfused rat liver SDI 157 induced a high sorbitol release and plasma samples of animals treated with SDI 157 induced a sorbitol accumulation in vitro in erythrocytes like SDI 158. SDI 157 seems to be a prodrug. In accordance with the polyol theory, the chronic administration of SDI 157 to diabetic rats accelerated the cataract development and depleted the lens of total and oxidized glutathione. Surprisingly, however, it accelerated the motor nerve conduction velocity in normal and diabetic rats, normalized the glomerular filtration rate in diabetic rats and did not induce retinal capillary lesions in normal rats or aggravate those in diabetic rats. At single oral doses up to 100 mg/kg, SDI 157, was well tolerated by diabetic and normal rats. Except for a reduction of drinking water consumption, the chronic administration of SDI 157 in drinking water at doses up to 100 mg/kg per day had no side effects in normal, diabetic and galactoselfructose-rich diet rats. PMID- 7986241 TI - Penetration of spin-labeled dihydrolipoate into the skin of hairless mice. Modification of epidermal and dermal polarity. AB - Electron paramagnetic resonance (EPR) imaging with the modulated field gradient technique is a novel method to investigate skin biophysical and biochemical properties employing specific nitroxide spin probes. Using this method, a distinct increase in polarity from epidermis towards lower dermis is observed with the spin label dit-butylnitroxide (DTBN). With proxylmaleimide a considerable increase in mobility is found, when epidermis is compared with dermal compartments. The effect of the natural antioxidant dihydrolipoate on skin membrane polarity was studied. Skin penetration of spin labeled dihydrolipoate was investigated by EPR imaging. The results indicate that dihydrolipoate also increases membrane polarity. The biophysical and biochemical changes in the epidermis and dermis as revealed by spatial imaging, provide indirect evidence for skin penetration of dihydrolipoate. This conclusion was supported by the finding that spin labeled derivatives of dihydrolipoate and lipoate were detected inside epidermis and dermis by EPR imaging. This study demonstrates the feasibility of EPR imaging to investigate pharmacodynamic and pharmacokinetic properties of spin labeled drugs in skin. PMID- 7986242 TI - Relative bioavailability of oral dosage forms of tenoxicam. AB - The bioavailability of tenoxicam (Ro 12-0068, Tilcotil, CAS 59804-37-4) from an effervescent tablet and an instant milk drink formulation relative to the commercial 20 mg tablet was investigated in a randomized cross-over study. Twelve healthy male volunteers (age 18-35 years; weight 63-95 kg) received on three different occasions a single oral tablet, an effervescent tablet or an instant milk drink (dissolved in water) with each dose containing 20 mg of tenoxicam. The wash-out period between two consecutive treatments was at least 5 weeks. Plasma concentrations after dosing were determined with a specific HPLC method. With the effervescent tablet and the milk drink, maximum concentrations were obtained at the same time (0.5-3.0 h) as with the reference tablet (0.5-4.0 h). Plasma peak concentrations appeared highest after the commercial tablet (mean +/- SD: Cmax 2.8 +/- 0.55 mg/l), but the difference to the effervescent tablet (2.7 +/- 0.41 mg/l) and the milk formulation (2.5 +/- 0.41 mg/l) was negligible. Similar mean elimination half-lives of 73, 77, and 77 h were obtained with the effervescent tablet, the milk drink, and the commercial tablet, respectively. Average bioavailability relative to the tablet was for the effervescent tablet and for the milk drink 96% with a coefficient of variation of 8%. The 90%-confidence intervals of the mean differences between the test and standard preparations in log-transformed AUC0-infinity and Cmax were within 20% around the respective mean parameter value calculated for the standard preparation allowing to conclude bioequivalence of the three oral formulations. PMID- 7986243 TI - Effects of essential phospholipids on the amino acid metabolism in whole body irradiated rats. AB - Ionizing radiation induces injury to cell membranes resulting in an increase of plasma amino acids concentration and catabolic response of the body. Essential phospholipids (EPL) administered before radiation protect the cell structures and can be used for their renewal. For this reason EPL are expected to have some effect on amino acid metabolism in radiation sickness. The adult male Wistar rats were injected with EPL in a dose of 125 mg EPL/kg b.w. (Essentiale) or saline solution. Three h later whole-body gamma irradiation with a single dose of 10 Gy was performed. Untreated pair-fed rats served as control. The rats were sacrificed 2 days after irradiation. In irradiated rats a decrease in body weight, increased concentrations of plasma amino acids, higher oxidation of branched chain keto acids in liver mitochondria, higher incorporation of leucine into liver proteins and decreased leucine incorporation into proteins of small intestine were observed. In EPL pretreated rats a longer survival time, a higher body weight, lower levels of plasma amino acids and higher protein synthesis in small intestine and in liver when compared with irradiated, saline treated rats were found. No significant changes were observed in branched chain amino acid oxidation measured by means of labeled ketoisocaproate in liver mitochondria. PMID- 7986244 TI - Effects of dietary fat levels on the absorption and tissue accumulation of probucol in the rat. AB - The effects of dietary fat level on the absorption and tissue accumulation of probucol (PB, CAS 23288-49-5) were studied in male Wistar rats. Addition of 1% PB (w/w) to the diets as compared to the diets without an addition (P) resulted in a decrease in the concentration of both serum and high-density lipoprotein (HDL) cholesterol as well as TBA-reactive substances (TBARS), without influencing food intake or growth. When rats were fed with the PB diet, the apparent intestinal absorption of PB was 7.9%, while the serum PB level was 5 micrograms/ml. The tissue distribution of PB, when expressed per g of tissue, was highest in the adrenal glands, followed by the liver, heart, epididymal adipose tissues, kidneys, lung, spleen, and testes. The addition of 10% olive oil (PBO) to the PB diet (w/w) appeared to double the PB diet-induced increase in apparent intestinal absorption and the serum concentration of PB. Furthermore, compared with the PB diet, the PBO diet caused 3- to 4-fold higher accumulation of PB in the liver and its subcellular fractions and 2-fold higher accumulation in the spleen. However, there was no further accumulation of the drug in the heart, kidneys, lungs, and testes. Incorporation of the drugs into adipose tissues was significantly lower with the PBO diet than with the PB diet. These results suggest that dietary manipulation leads to changes in the intestinal absorption and serum level of PB. PMID- 7986245 TI - [Absolute bioavailability of folic acid after oral administration of a folic acid tablet formulation in healthy volunteers]. AB - 5 mg folic acid were administered in two sessions to 9 female and 8 male healthy subjects within a balanced 2-way crossover trial either as one Folsan tablet (CAS 59-30-3, test preparation A) or as 2.5 ml of an injection solution (Folsan 2, reference preparation B). Folic acid was determined in serum and urine collected in fractions over 12 h after administration by means of a radioassay. Before each session a saturation period of 9 days duration was performed by administering 1 tablet per day containing 5 mg folic acid followed by a 4-day wash-out period. The mean predose serum level of folic acid amounted to 17.9 +/- 5.62 ng/ml before the oral and 18.2 +/- 5.73 ng/ml before the intravenous administration. The post dose serum levels were corrected with the individual predose levels. After oral administration of test preparation. A a mean peak serum concentration of 243 +/- 33.0 ng/ml (Cmax) was obtained after 2.24 +/- 0.85 h (tmax). The mean area under the corrected serum level time curve was determined with 1160 +/- 177 ng x h/ml (AUC(0-12)). 6 min after intravenous administration serum levels ranged from 559 to 1490 ng/ml. Following correction with the individual predose levels the mean area under the curve amounted to 1550 +/- 249 ng x h/ml. The individual bioavailability ratios of AUC(0-12) (A versus B) varied between 49.3% and 96.7%. The mean absolute bioavailability of folic acid was 76.2% +/- 13.8% (p < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7986246 TI - Evidence for a second site of absorption of veralipride in the human small intestine. Use of a new drug delivery telemetric shuttle. AB - A new telemetric shuttle was used to coadminister veralipride (CAS 66644-81-3) and veralipride-D3 in order to test the assumption that veralipride is absorbed at two sites of the small intestine. Two different pharmacokinetic approaches were used to interpret the obtained data. According to the results, the second site of absorption of veralipride is located at a distance corresponding to 2/3 of the total length of the small intestine. PMID- 7986247 TI - Synthesis and activity of new linear and cyclic peptide T derivatives. AB - Linear and head to tail cyclic hexapeptide analogs (Xaa-Thr-Thr-Asn-Tyr-Thr, Xaa = D-Asp or D-iso-Asp) of peptide T were prepared and tested for human monocyte chemotaxis. All new compounds showed significant bioactivity. In particular, the conformational restriction introduced into cyclo(-D-iso-Asp-Thr-Thr-Asn-Tyr-Thr-) was very suitable for CD4 receptor binding. The cyclic peptides also proved to be highly resistant to degradation by plasma or brain enzymes. PMID- 7986248 TI - Synthesis and antimicrobial activity of dihydrofurobenzoxazolin-2(3H)-ones and their derivatives. AB - A series of dihydrofurobenzoxazolin-2(3H)-ones and their derivatives were synthesized. The structures of the compounds have been elucidated by IR, mass, 1H NMR spectra and elementary analysis. The in vitro activity of these compounds was investigated against Gram-positive and Gram-negative bacteria and also against Candida albicans. 7,7-Dimethyl-7,8-dihydro-furo[2,3-g]benzoxazolin-2(3H)-one (compound 2) proved to be more potent than compound 1. Compound 3 also showed significant activity against all the microbes tested. Compounds 4 and 5 were more effective against Gram-positive bacteria than Gram-negative bacteria but inactive against C. albicans. PMID- 7986249 TI - General pharmacology of cis-malonato[4R,5R)-4,5-bis-(aminomethyl)-2-isopropyl-1,3 dioxolane]platinum(II). AB - The general pharmacological properties of cis-malonato-[(4R,5R)-4,5- bis(aminomethyl)-2-isopropyl-1.3-dioxolane]platinum(II) (SKI 2053R, CAS 146665-77 2), a new potential anticancer agent, were investigated in mice, rats, guinea pigs, rabbits, cats and dogs. Intravenous administration of SKI 2053R had no effect on the central nervous system. SKI 2053R had no effect on the autonomic nervous system and smooth muscles except that it slightly inhibited the spontaneous motility of isolated rabbit ileum at a concentration of 5 x 10(-5) g/ml. SKI 2053R did not adversely affect the respiratory-cardiovascular system, gastrointestinal system, neuromuscular junction, or renal function. SKI 2053R did not significantly alter the levels of serum glucose, serum free fatty acid and plasma lactate, and did not induce hemolysis. SKI 2053R did not affect blood coagulation mechanism and liver function. SKI 2053R did not exhibit anti inflammatory activity. It was observed that SKI 2053R increased the formation of hemolytic plaque by spleen cells of sensitized mice at high doses (10 mg/kg and 35 mg/kg). Therefore, it is concluded from these general pharmacological studies that SKI 2053R at the doses showing antitumor activity does not induce severe adverse effects on the central nervous, autonomic nervous, respiratory cardiovascular, gastrointestinal, peripheral nervous, and other systems in experimental animals. PMID- 7986250 TI - General pharmacology of gemcitabine hydrochloride in animals. AB - Gemcitabine (2',2'-difluorodeoxycytidine monohydrochloride, LY188011 hydrochloride, CAS 122111-03-9) is a nucleoside analog with a broad spectrum of antitumor activity in murine models and is currently undergoing clinical evaluation. The profile of the pharmacological effects of this agent was assessed in studies evaluating the cardiovascular and respiratory systems, renal function, the gastrointestinal system, the central nervous system, and the autonomic nervous system. In vivo doses ranged from 0.15 to 300 mg/kg given by the intravenous route, while in vitro concentrations up to 1 x 10-3 mol/l were used. Gemcitabine was inactive in the autonomic nervous system, gastrointestinal function, and central nervous system studies. Only minimal changes were seen in the cardiovascular and respiratory study, with a slight decrease in pulmonary arterial pressure at the mid dose and a stroke volume increase at the high dose. In the renal function studies, a slight decrease in the urine pH at the high dose and decreased serum creatinine at the mid dose levels were observed. In summary, gemcitabine had minimal effect in these pharmacodynamic studies. These results indicate that gemcitabine has a low potential to produce adverse pharmacologic effects. PMID- 7986251 TI - General pharmacology studies on recombinant human follicle stimulating hormone. AB - Follicle stimulating hormone (FSH) is a heterodimeric glycoprotein secreted by anterior pituitary cells. Its main actions are to lead ovarian follicles to maturation and to maintain spermatogenesis. Up to now the FSH preparations used in clinical practice (CAS 9002-68-0 and CAS 97048-13-0) have been purified from human postmenopausal urine. Only recently, a product was successfully obtained by recombinant-DNA technology, r-hFSH (Gonal-FTM). This recombinant protein is highly pure and has a very high specific activity. In view of its clinical use, this hormone has been submitted to an extensive panel of general pharmacology studies with the aim of defining its pharmacological profile and determine possible side effects not related to the main therapeutic action. Subcutaneous or intravenous doses of 5 to 500 IU/kg were assayed in several tests for their effects in vivo on various systems in different animal species. The substance under study was also tested in vitro on isolated guinea-pig ileum preparations at final concentrations of 0.05 to 2 IU/ml of bath. The results of this study showed that r-hFSH does not influence the general activity and behaviour of mice, as measured by the multidimensional Irwin's test. Similarly, the drug was not found to affect the normal body temperature in rats nor the locomotor activity in mice for as long as 7 h post-injection; in addition, it was not found to induce pharmacologically significant alterations of the cardiovascular and respiratory parameters in rats and dogs.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7986252 TI - New 4-arylaminopiperidines with antihypoxic and anticonvulsive activity. AB - Several new bioanalogues of (+/-)-N-methyl-N-(1-[3-(4-fluorophenoxy)-2-hydroxy propyl]piperidin++ +-4-yl) benzothiazol-2-amine (1, sabeluzole, CAS 104383-17-7) were prepared by reacting 1,2-epoxy-3-aryloxypropanes with 4 arylaminopiperidines. Some of these derivatives showed enhanced activity in the potassium cyanide hypoxia test and in the pentetrazol convulsion test in mice compared to 1. PMID- 7986253 TI - Synthesis and effect on free radical processes on some substituted morpholine derivatives with potential biologic activity. AB - Since a number of 2-hydroxy(alkoxy)-2-phenyl-4(5,6)-(tri)alkyl-morpholines presented antioxidant and interesting biologic activity which may implicate free radical processes, some 2-hydroxy(alkoxy)-2-biphenyl-4-methyl-morpholine derivatives were prepared in an attempt to synthesize more potent antioxidants with interesting biologic action. The 2-hydroxy-2-biphenyl-4-methyl-morpholine was prepared by reacting the N-methyl-ethanolamine with the p-phenyl phenacylbromide, the 2-hydroxy-derivative formed after spontaneous cyclisation gave the 2-alkoxy-2-biphenyl-4-methyl morpholines by an acid catalyzed ketal formation. The lipophilicity of the synthesized compounds was determined by the reversed phase TLC technique as RM values. The synthesized 2-biphenyl substituted morpholines were evaluated for their antioxidant activity on hepatic microsomal lipid peroxidation and on hydroxyl radical mediated oxidation of dimethylsulfoxide. The synthesized compounds were found to possess potent antioxidant activity. A possible mechanism was proposed for the antioxidant properties while lipophilicity was found not to be an important determinant of this property. PMID- 7986254 TI - Effects of L-ascorbic acid 2-[3,4-dihydro-2,5,7,8-tetramethyl-2-(4,8,12 trimethyltridecyl)-2H-1- benzopyran-6yl-hydrogen phosphate] potassium salt on cerebral energy state and consciousness recovery following transient forebrain ischemia in gerbils. AB - Effect of L-ascorbic acid 2-[3,4-dihydro-2,5,7,8-tetramethyl-2-(4,8,12 trimethyltridecyl)-2H -1- benzopyran-6yl-hydrogen phosphate] potassium salt (EPC K1, CAS 127061-56-7), a diester of alpha-tocopherol and ascorbic acid, on transient cerebral ischemia was studied in Mongolian gerbils. Cerebral energy metabolism and intracellular pH (pHi) were estimated employing in vivo 31P nuclear magnetic resonance (NMR) spectroscopy. Intraperitoneal injection of EPC K1 (5 or 10 mg/kg) prior to ischemia significantly ameliorated pHi reduction in a dose dependent manner during ischemia. After reperfusion, energy and pHi recoveries were significantly faster in the EPC-K1 groups than in the control group. EPC-K1 (10 mg/kg) significantly reduced the extent of cerebral edema. Moreover, administration of EPC-K1 immediately after reperfusion significantly shortened the consciousness recovery in a dose dependent manner. The results suggest that EPC-K1 may exert protective effects on ischemic brain and may have therapeutic value in ischemic stroke. PMID- 7986255 TI - [Evidence of a pharmacokinetic-pharmacodynamic relationship between pharmaco-EEG in healthy subjects after administration of cyclandelate]. AB - In an open randomized cross-over study 800 mg cyclandelate (Natil, CAS 456-59-7) was applicated to 24 young, male volunteers. Before and during 24 h after application of a single dose a 17-channel, quantitative topographical pharmaco EEG was recorded. A significant increase of the spectral power density was observed in the alpha 2, beta 1 and beta 2 frequency bands starting 2 h after application until 4.5 h. The increase in beta 1 and beta 2 power was observed in the parietocentral area of the cortex. The difference between the circadian development of the EEG power and the development after medication was obvious after 3 until 4.5 h. For the beta frequencies only a weak statistical confirmation could be obtained, but for the alpha 2 frequency a significant difference between the circadian and the EEG power under cyclandelate was found using the sign test. Altogether a quantitative effect on brain activity was detected after oral application of cyclandelate, reaching its maximum before the blood concentration of the metabolites cyclandic glucuronide and mandelic acid reached their peak heights. PMID- 7986257 TI - Milestones in the treatment of acute myocardial infarction. AB - The last half-century has witnessed momentous improvement in the treatment of acute myocardial infarction resulting in significantly reduced mortality. The most significant advances are suggested to be "chair" treatment, coronary care units, anticoagulation and thrombolytic therapy. PMID- 7986256 TI - Distribution of the 75-kD low-affinity nerve growth factor receptor in the primate peripheral nervous system. AB - Disruption of the 75-kD low-affinity nerve growth factor (NGF) receptor (p75) has been shown to result in sensory and sympathetic nervous system deficits (Lee et al., 1992a,b). In order to establish precisely which subsets of neurons are capable of responding to neurotrophins (NTs) through the low-affinity NGF receptor, p75 was localized in the primate autonomic and somatic sensory nervous systems. In the autonomic system, cell bodies of some parasympathetic and enteric neurons expressed detectable levels of p75, whereas all sympathetic neurons expressed the protein. In the sensory system, some, but not all, cell bodies were labeled in cranial and spinal sensory ganglia and in the mesencephalic nucleus. Some peripheral and central projections of the sensory neurons were also labeled. Centrally, most of the labeled processes were found in regions containing primarily small unmyelinated fibers, including lamina II of Rexed and areas of the solitary tract and nucleus. Peripherally, labeled processes were associated with unmyelinated nerves and specialized structures such as taste buds and Meissner corpuscles, but not with myelinated processes. This study indicates that the subset of neurons in the autonomic nervous system likely to be capable of responding to neurotrophins is broader than generally thought, and that p75 expressing neurons tend to be clustered. Moreover, in the sensory nervous system p75 is expressed by most cell bodies, but expression in their projections is restricted both peripherally and centrally to unmyelinated processes and nerve terminals. PMID- 7986258 TI - Uptake and storage of retinol and retinyl esters in bone marrow of children with acute myeloid leukemia treated with high-dose retinyl palmitate. AB - Twenty-one children with AML, who achieved complete remission with cytostatics, were treated with high doses of retinoids after remission was achieved. They were given 52 mumol retinyl palmitate/m2 (50,000 International Units/m2) daily for at least 2 years thereafter. Thirteen of the children are still in complete remission with a mean observation time of 103 months. Due to the positive effects of retinoids seen in the treatment of AML, we have studied uptake of lipoprotein associated retinyl esters in bone marrow cells and peripheral leukocytes in vivo. An oral load of 104 mumol/m2 (100,000 International Units/m2) retinyl palmitate resulted in a doubling of the concentration of total retinol in bone marrow cells and peripheral leukocytes after 5 hours. However, in the fasting state no significant difference was observed between the content of total retinol in bone marrow cells from controls and from patients receiving retinyl palmitate daily for years. Our study suggests that bone marrow cells take up retinyl esters postprandially, but do not store retinoids. PMID- 7986260 TI - Acute myeloblastic leukemia with a pericentric inversion of chromosome 6 in a child with Down syndrome. AB - Cytogenetic analysis of bone marrow cells demonstrated a pericentric inversion of chromosome 6 when acute myeloblastic leukemia (AML) was diagnosed in a 15-month old child with Down syndrome. The abnormal clone with inv(6)(p24q16) was associated with FAB-M1 AML and disappeared when a complete remission was achieved. This is a unique cytogenetic abnormality for FAB-M1 AML in a child with Down syndrome and, to our knowledge, is only the second case of a pericentric inversion of chromosome 6 reported in AML. PMID- 7986259 TI - Differential effects of transferrin receptor antibodies on growth and receptor expression of human lymphocytic and myelocytic cell lines. AB - J64, a monoclonal antibody against the human transferrin receptor, has been shown to induce interleukin-2 production by HUT78 cells. It also causes growth inhibition of several cell lines and stimulated lymphocytes. These effects were also present using transferrin-free culture conditions. In this paper, we dissect cell membrane and intracellular events after binding of J64 and other transferrin receptor antibodies. Incubation of HUT78 and several other cell lines with J64 resulted in an increased number of receptor molecules expressed on the cell surface in contrast to a downmodulation seen with other monoclonal antibodies to the transferrin receptor. This upregulation after treatment with J64 was not due to an increased concentration of transferrin receptor mRNA in these cells or a higher protein synthesis rate. We therefore suggest that J64 causes a redistribution of transferrin receptor molecules from intracellular pools to the cell surface. Additional experiments investigating signal transduction mechanisms revealed no influence of J64 on intracellular Ca2+ concentrations or translocation of protein kinase C. However, an increase of transferrin receptor phosphorylation was seen in HL60 cells after treatment with phorbolester or J64. This phosphorylation of the transferrin receptor might be a signal transduction pathway involved in activation and growth control. PMID- 7986261 TI - Maturation of the behavioral and neuroendocrine differences between the Roman rat lines. AB - The behavioral and/or neuroendocrine reactivity to psychological (open-field exposure) and physiological (CRF challenge) stimulations, as well as adrenal tyrosine hydroxylase (TH) and phenylethanolamine N-methyl transferase (PNMT) activities were measured, at different ages, in the Roman high avoidance (RHA) and Roman low avoidance (RLA) rat lines that have been genetically selected on the basis of their divergent active avoidance behavior. The highest locomotor activity in the open field, associated to blunted prolactin and renin reactivity to an emotional stress and lower specific TH and PNMT activities, characterized the RHA rats of all ages. HPA axis reactivity to psychological and/or physiological stimulations was identical in young animals (14 weeks old) of the two lines. Nevertheless, it displayed with age maturation processes, since the amplitude of postopen-field secretion peak for ACTH was larger in RLA rats from 20 weeks on, the response to CRF being not increased until 42 weeks. These maturation processes could result from genetically influenced changes related to environmental stimulations. Therefore, the Roman lines may be an excellent model to study the interactions between the genetic and developmental factors controlling the coupling between both behavioral and neuroendocrine functions. PMID- 7986262 TI - Microparticle release from platelets by leukemic cell lines. PMID- 7986263 TI - ATP/ADP antiporter is involved in uncoupling of plant mitochondria induced by low concentrations of palmitate. AB - Carboxyatractyloside partially restored the transmembrane electrical potential difference (delta psi) dissipated by low concentrations of palmitate in pea stem mitochondria. This effect was more marked when mitochondria from sunflower were assayed. It is suggested that the ATP/ADP translocator is involved in the free fatty acid-induced uncoupling of oxidative phosphorylation in plant mitochondria, only when its level is sufficiently high and the concentration of the fatty acid is low to collapse only partially delta psi. PMID- 7986264 TI - Treatment of orbital capillary haemangioma with interferon. AB - BACKGROUND: Capillary haemangiomas are vascular tumours of childhood characterised by proliferative and involutional phases and affecting 1% to 2% of newborns. Recently, recombinant interferons have been used in the treatment of life and sight threatening complications of these tumours. METHODS: The history, results of examination, investigations, management and outcome of two patients with sight-threatening orbital capillary haemangiomas treated with recombinant interferon alpha-2a and 2b respectively were reviewed. RESULTS: Orbital and systemic lesions displayed good response to interferons. Side effects noted were transient pyrexia and elevated serum aminotransferase levels. Disturbed liver function test results occurred in one case and normalised with temporary cessation of therapy. CONCLUSIONS: The interferons are a useful alternative treatment of orbital capillary haemangioma in selected cases. PMID- 7986265 TI - Gastric vascular ectasia in patients undergoing bone marrow transplantation. AB - The authors reviewed all gastric biopsy specimens from patients who had undergone bone marrow transplantation at our institution between 1986 and 1991. Ten of 28 patients had gastric vascular ectasia (GVE), a distinct lesion consisting of telangiectatic vessels within the superficial gastric mucosa. All patients undergoing bone marrow transplantation had received a standard chemotherapeutic transplantation regimen consisting of busulfan and cyclophosphamide without total body irradiation. Eight of the 10 patients with GVE had evidence of upper gastrointestinal tract bleeding, as compared with 4 of 18 patients without GVE. In all 10 patients with GVE, the results of liver chemistry analyses were abnormal. Five patients had hepatic veno-occlusive disease, and 8 patients had graft-versus-host disease. Endoscopic biopsy samples of GVE showed markedly dilated vascular spaces similar to those seen in gastric antral vascular ectasia and diffuse antral vascular ectasia. However, no thrombi were identified in these enlarged vessels. Digital morphometry showed the mean cross-sectional area of GVE vessels was significantly greater (P < .001, Wilcoxon's rank-sum test) than the mean vessel areas of 10 chemical gastritis and 10 normal antral (control) biopsy samples. Gastric vascular ectasia may be a significant cause of gastrointestinal bleeding in patients undergoing bone marrow transplantation. The pathogenesis of GVE is unknown; transplantation regimen toxicity may play a role. PMID- 7986266 TI - Motility and chemotaxis in Bacillus sphaericus. Dependence upon stage of growth. AB - Chemotaxis and motility of B. sphaericus 2362 were monitored as the function of a batch culture age. It was found that both functions changed independently during growth of the culture. Motility was low until the late logarithmic stage ensued, whereafter it increased sharply. The ability of cells to respond to chemoeffectors peaked at the mid-logarithmic phase. A major methyl-accepting chemotaxis protein (P53, M(r) = 53 kDa) was identified. The extent of label incorporation in this protein from L-[methyl-3H]methionine was maximal in mid- and late logarithmic phases of the growth. Cells in stationary cultures incorporated very low amounts of the label. At any stage, the labeling was maximal in starved cells; it was almost abolished in cells pre-incubated with amino acids. Although extents of P53 labeling in mid- and late logarithmic cells were similar, late logarithmic cells demonstrated a considerably impaired chemotaxis. Supermotile sporulating cells were practically insensitive to environmental stimuli. The difference in development of sensory and locomotive functions may be interpreted as an adaptive response. A well developed sensory apparatus would allow vegetative cells to adapt efficiently to fluctuating attractant gradients. Insensitive sporulating cells would tend to disperse randomly from the nutrient-exhausted area. Thus, spore formation would occur in larger volume of the habitat, increasing the chance of the microbial population to survive. PMID- 7986267 TI - WH14, a marker of precursor-B leukemia/lymphoma is available for paraffin embedded section. PMID- 7986268 TI - [Female and male nurses in child and juvenile psychiatry. Chances for further education in a new specialty]. PMID- 7986269 TI - The myth of suicide prevention by general practitioners. PMID- 7986270 TI - Apoptosis or retinoblastoma: alternative fates of photoreceptors expressing the HPV-16 E7 gene in the presence or absence of p53. AB - A transgenic mouse model for retinoblastoma was produced previously by directing SV40 T antigen expression to retinal photoreceptor cells using the promoter of the interstitial retinol-binding protein (IRBP) gene. This gene becomes active prior to the terminal differentiation of photoreceptors. Because T antigen transforming activity is attributable, at least in part, to the inactivation of the retinoblastoma (pRb) and p53 tumor suppressor proteins, we addressed the role of p53 in the development of retinoblastoma in mice. Transgenic mice expressing HPV-16 E7 under the control of the IRBP promoter were generated to inactivate pRb in photoreceptors while leaving p53 intact. Rather than developing retinoblastomas, the retinas of these mice degenerate due to photoreceptor cell death at a time in development when photoreceptors are normally undergoing terminal differentiation. The dying cells exhibit the histological and ultrastructural features of apoptosis and contain fragmented DNA. p53 is required for the induction of apoptosis in this model, because mice expressing E7 in a p53 nullizygous background develop retinal tumors instead of undergoing retinal degeneration. PMID- 7986271 TI - ESBRA award 1994. 11-12 May, Cardiff. PMID- 7986272 TI - Alcohol treatment services in Russia: a worsening crisis. AB - This paper reviews the state of alcohol treatment services in Russia. There have been some recent improvements, for example the introduction of confidentiality in treatment, the closure of correctional centres, and the payment of state benefits to in-patients. However, there remains a considerable stigma attached to a diagnosis of alcoholism. Although new approaches to treatment have been promulgated, in practice Russian treatment methods remain idiosyncratic with little in the way of psychotherapy. Many techniques utilise placebos and persuasion, with the patient as a passive recipient. Services are generally of a poor quality, and underfunded and medical specialists are poorly trained. To improve matters it is suggested that there will need to be: (1) changes in knowledge and attitude among the general population and within the specialist services; and (2) a continuing exchange of ideas and specialists between Russia and the West. PMID- 7986273 TI - Early diagnosis and treatment of alcoholism: the Japanese experience. AB - The current status and problems concerning the early identification, diagnosis and treatment of alcoholism in Japan are outlined in this article. With regard to the early diagnosis of alcoholism, we focus on the following four aspects: (1) the drinking culture in Japan and the difficulties in early diagnosis of drinking problems because of this culture, (2) the social system which serves to the early diagnosis of alcoholism, (3) the education of specialists, and (4) screening tests and biological markers of alcoholism. The number of facilities offering specialized treatment of alcoholics has sharply increased in recent years, but it is clear that such facilities are still not sufficient to meet the demand. It also emphasizes that diversification of alcohol treatment facilities is essential to meet the therapeutic needs of newly emerging subgroups such as women, young people and the elderly. Finally, the characteristics of the two self-help groups in Japan, Danshukai (Japan Sobriety Association) and Alcoholics Anonymous (AA), are described and compared. PMID- 7986274 TI - Effects of ethanol treatment upon sources of reactive oxygen species in brain and liver. AB - Sources of reactive oxygen species (ROS) generation have been compared in microsomal and mitochondrial fractions of brain and liver from ethanol-treated and control rats. Rates of ROS generation were quantitated with the fluorescent probe precursor, 2'7'-dihydrochloroflurescin diacetate, whose validity has been previously established. The production of active pro-oxidant species was measured in the presence of various selective inhibitors of enzymes potentially able to contribute to oxidative events. Several steps in the arachidonic acid cascade appeared to constitute a large fraction of total ROS generating capacity. Chelation of intrinsic iron with desferoxamine greatly reduced such capacity, especially in cerebral tissue. Aldehyde oxidases were active in generating ROS in both tissues. Inhibition of catalase dramatically enhanced ROS in liver but not in brain microsomes. While no ethanol-treatment effects were found in brain, there was evidence that ethanol consumption decreased hepatic levels of catalase, aldehyde oxidases and cyclooxygenase. However, despite these reductions, total basal ROS production was elevated in liver but not brain fractions from treated animals. The addition of an exogenous iron salt enhanced ROS formation to a lesser extent in ethanol-consuming rats than in controls. The elevation of basal hepatic ROS levels in ethanol-treated rats may thus be compatible with the release of cytosolic low molecular weight free iron compounds into the cytosol. PMID- 7986275 TI - Ethanol elimination in alcohol-treated pregnant rats. AB - The effects of chronic intake of alcohol on ethanol elimination were studied in 20-day pregnant rats, in their foetuses, and in virgin rats. Experimental animals received ethanol in drinking water (from 10% to 25% in 2 months) (alcohol group), whereas controls drank only water. At the end of chronic exposure, alcohol dehydrogenase activity was determined in stomach and liver and cytochrome P-450 was measured in liver. In a complementary assay, the same experimental groups of rats were given an acute dose of ethanol (2 g/kg body wt, 25% w/v) either intragastrically or intraperitoneally, at the end of the chronic exposure, to determine first-pass ethanol metabolism and pharmacokinetic parameters of its elimination. Significant differences were found between alcohol and control groups for liver and stomach alcohol dehydrogenase activity in pregnant rats. Only in virgins did chronic alcohol treatment significantly increase the liver cytochrome P-450 content. In virgin rats, the first-pass metabolism of ethanol was lower in the alcohol group than in control. By contrast, in control rats, the first-pass of ethanol was lower in pregnant, than in virgin, rats. The metabolic rate of ethanol elimination (mg/kg body wt/hr) was clearly enhanced in alcoholic virgin rats, demonstrating that this model of chronic alcoholism induces metabolic tolerance to ethanol. In alcoholic pregnant rats, a surprisingly low theoretical volume of body ethanol distribution (55 ml/100 g body wt vs. 80 ml/100 g body wt in the other groups) masked their metabolic tolerance to ethanol. This preliminary study should be taken into account when evaluating the effects of chronic or/and acute alcohol intake during pregnancy on the circulating ethanol levels in foetuses and on future development of the foetal alcohol syndrome. PMID- 7986276 TI - Tolerance and dependence in high alcohol sensitivity (HAS) and low alcohol sensitivity (LAS) rats after chronic alcohol intoxication by inhalation. AB - In rats selected for their differences in sleep time following acute administration of ethanol (high or low alcohol sensitivity: HAS or LAS), alcohol chronic tolerance and behavioural dependence were determined. Tolerance was assessed by calculating the interval between the loss and regain of the righting reflex following an acute administration of ethanol (4 g/kg body wt), after intoxication by inhalation of ethanol vapour for 3 weeks. The importance of behavioural dependence was estimated by measuring the ethanol intake in a free choice situation water/ethanol (10% v/v), after intoxication by inhalation for 4 weeks. The two HAS and LAS lines did not show any behavioural dependence, while they developed a significant tolerance to the hypnotic effect of ethanol, which was more marked for the LAS line. PMID- 7986277 TI - The in vitro binding of acetaldehyde to collagen studied by neutron diffraction. AB - The location of acetaldehyde binding sites in the axial unit cell of tendon collagen was investigated by neutron diffraction. Acetaldehyde forms spontaneous cross-links with specific residues in collagen. The use of deuterated acetaldehyde increased the neutron scattering length of these groups. The introduction of deuterated acetaldehyde at specific locations allowed the acetaldehyde-reacted collagen to be treated as multiple isomorphous derivatives for neutron fibre diffraction. The low resolution axially projected structure was determined using amplitudes of the first eight meridional reflections (d = 67 nm). Results indicate that the process of acetaldehyde labelling takes place at different rates at different sites within the collagen fibril. The position of acetaldehyde attachment correlates well with the position of lysine and hydroxylysine residues especially in the regions of the molecular termini. This information is relevant to the process of cirrhosis and fibrosis of the liver since adduction of collagen by acetaldehyde may interfere with normal Schiff base cross-link formation at the C- and N-termini. This may result in subsequent alterations in the intra- and inter-molecular cross-linking pattern of collagen molecules. PMID- 7986278 TI - Influence of regular alcohol consumption on uricaemia in unselected healthy individuals. AB - We analysed serum uric acid concentrations in a group of healthy male and female volunteers in Cordoba (Spain) possessing varying nutritional habits, in order to correlate them with their usual alcohol intake as measured according to a protocolized, blind dietary questionnaire. There was no significant correlation between the serum uric acid and the amount of alcohol regularly drunk by either male or female individuals. These results suggest that a moderate alcohol intake has no effect on uricaemia in healthy individuals. PMID- 7986280 TI - The effect of ethyl alcohol on the sensitivity of upper airway reflexes. AB - The effect of ethyl alcohol on upper airway reflex sensitivity (UARS) has not been previously investigated in humans. Using a technique that we have previously described, intermittent breaths of low concentrations of ammonia vapour were used to measure the effect of ethyl alcohol 0.55-0.66 g/kg on UARS in ten healthy male volunteers. The depression of upper airway reflexes that occurred following ingestion of ethyl alcohol was maximum at 60 min and returned to baseline by 150 min. This dose of ethyl alcohol was insufficient to produce statistically significant depression of UARS. The blood alcohol levels achieved showed a wide range with a mean of 78.9 mg/100 ml (SEM 10.3). Individual subjects who had blood alcohol levels in excess of 100 mg/100 ml displayed much greater depression of UARS. In conclusion, 0.55-0.66 g/kg ethyl alcohol given to healthy male volunteers does not produce significant depression of UARS as measured using an ammonia stimulus technique. PMID- 7986279 TI - Correlations between acetaldehyde-modified haemoglobin, carbohydrate-deficient transferrin (CDT) and haematological abnormalities in chronic alcoholism. AB - Serum levels of carbohydrate-deficient transferrin (CDT), the proportions of eight haemoglobin fractions separated by cation exchange liquid chromatography, indices of liver function and various haematological parameters were determined in most of a group of 49 chronic alcoholics who had misused alcohol for at least the preceding 3 months and in 15 healthy non-alcoholic control subjects. The percentages of alcoholics giving abnormally high values for gamma-glutamyl transferase (GGT) activity, CDT levels, GGT activity or CDT levels or both, and aspartate aminotransferase (AST) activity were, respectively, 73.0, 71.0, 87.1 and 64.4. The percentages of patients giving abnormally high values for the proportion of HbA1a, proportion of HbA1ach, proportion of HbA1a or HbA1ach or both, MCH, MCV and red cell distribution width (RDW) were, respectively, 46.8, 25.5, 55.3, 55.3, 36.2 and 29.8. Reduced values for the red cell folate concentration, lymphocyte count and platelet count were found in 36.2%, 6.4% and 17.0%, respectively, of the alcoholics. When compared with the control subjects, the group of alcoholics showed statistically significant increases in the mean values for the MCV, MCH, MCHC and RDW and statistically significant decreases in the mean values for the haemoglobin distribution width (HDW) and the logarithms of the holo-transcobalamin II concentrations and the platelet count. The logarithms of the CDT values correlated directly with the MCV and MCH and inversely with the logarithms of the lymphocyte or platelet counts and the HDW, suggesting but not proving that the haematological changes in chronic alcoholism may be at least partly related to defective glycosylation of the constituents of developing blood cells or, possibly, of haemopoietic growth factors.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7986282 TI - Towards a concept of sensible drinking and an illustration of measure. AB - The major focus of research on alcohol is not on the majority who drink without problems, but on the small minority who have extreme problems. Difficulty in conceiving, measuring, and analyzing non-problem drinking lies in the exclusively problem-drinking orientation of most drinking measures. Drawing on conventionally used scales (e.g. Short Michigan Alcoholism Screening Test) and other established concepts in the alcohol literature (e.g. craving, hangover), a set of 24 items was selected to classify all persons in a sample from Tecumseh, Michigan, as to their alcohol-related behaviors (N = 1266). A Sensible-Problem Drinking Classification (SPDC) was developed with five categories: very sensible, sensible, borderline, problem, and impaired. A variety of known alcohol and psychosocial variables were related monotonically across these categories in expected directions. Ethanol ounces per week was only modestly related to SPDC groups: R2 = 0.09 for women, R2 = 0.21 for men. The positive relationship of problem and non-problem SPDC groups to high and low blood pressure was P = 0.07, while ethanol (oz/week) was uncorrelated to blood pressure (mm Hg) in this subsample (N = 453). The development of SPDC requires additional items measuring self and group regulatory alcohol behavior. However, this initial analysis of no problem subgroups has direct import for public health regulation of alcohol use by providing a model of a sensible view of alcohol use. PMID- 7986281 TI - Identification and characterisation of alcohol-induced flushing in Caucasian subjects. AB - The prevalence of the alcohol-flushing reaction was assessed in a group of healthy Caucasian medical students (200) by self-reporting and was found to occur in approximately 50% of female and 8% of male subjects. In most of the alcohol flushers there were other family members similarly affected. The presence of this side-effect after a small quantity of alcohol did not necessarily decrease the amount of alcohol consumed. A test dose of ethanol (0.4 g/kg body weight) confirmed the presence of the alcohol-induced flushing, which was of much shorter duration and intensity than that of the Oriental alcohol-induced flusher, as measured by laser Doppler velocimetry, and was not associated with high circulating concentrations of acetaldehyde. Topical administration of 5 M acetaldehyde showed an enhanced erythema in Caucasian flushers compared to non flushing controls. This effect was not observed with topical ethanol. Low erythrocyte ALDH1 activity was found in all Caucasians (n = 30) who showed the alcohol-induced flushing reaction. PMID- 7986283 TI - Characteristics of violent alcoholics. AB - This study is based on interviews with 53 male alcoholics. Its purpose was to study the relationship between childhood conditions, history of alcohol and drug misuse and assaultive and suicidal behaviour. Fifty-seven per cent of the alcoholics reported a history of violent behaviour. Hidden violence, often towards women, was common. One-third of the violent patients had a history of attempted suicide compared to 17% in the non-violent group. The assaultive alcoholics also had a more violent childhood, a higher proportion of fathers with alcohol problems and had started drinking earlier in life. Drug addiction was much more common in this group too. We find support for our hypothesis that there is a positive correlation between violence in the parental home and assaultive and suicidal behaviour and drug misuse later in life. When violent and non violent alcoholics are compared many of the same characteristics appear as when suicidal and non-suicidal and type 2 and type 1 alcoholics are compared. This study raises the question of adding attempted suicide as a characteristic of the type 2 alcoholic. PMID- 7986285 TI - Why, where and with whom do Israeli teenagers drink? To whom do they turn for help with alcohol problems? AB - This article describes preferred sources of support after having drinking problems, reasons for drinking and the social context of drinking of 1458 Israeli adolescents in the North of Israel in winter 1992. The article analyses the results by gender, grade and place of living (large city, small or developing town, kibbutz, religious settlement). Most teenagers drink with same-age friends, their preferred location of drinking is the pub and enjoyment is their most prevalent reason for drinking. The majority of the sample chose parents as the main source of support in cases of having problems with alcohol. The study provides pointers towards environmental approaches in the prevention of problem drinking. PMID- 7986284 TI - Occupational risk factors in patients with alcoholic or non-alcoholic liver disease. AB - The present study examines the presence of specific occupational risk factors in a group of patients suffering from alcoholic liver disease compared with a group of patients with non-alcoholic liver disease. The first group was more dependent on alcohol, with fewer social or psychological alcohol-related problems. The majority of them were employed, although more likely to be employed in traditional 'high risk' occupations. They showed lower job satisfaction, and the total sum of all previously reported occupational risk factors was highly significant. This was the first empirical evidence in support of the importance of the specific occupational risk factors previously postulated. PMID- 7986286 TI - Certification in child neurology by the American Board of Psychiatry and Neurology. PMID- 7986287 TI - Brain lesions of fetal onset in encephalopathic infants with nonimmune hydrops fetalis. AB - Nonimmune hydrops fetalis (NIHF) comprised 79% (45/57) of all infants with hydrops fetalis at our institution over a 6-year period. Thirty-seven infants with NIHF were liveborn. One or more electroencephalograms were performed on 40% of liveborn infants (15/37); the majority (87%) were moderately to markedly abnormal, including burst suppression, lack of background, multifocal sharp waves, excessive discontinuity, and disorganization reflecting significant neonatal encephalopathies. Postmortem neuropathologic examinations were performed in 86% of infants with NIHF who died or were stillborn, 81% of whom demonstrated intrauterine brain insults including microcalcifications, cerebral and/or cerebellar hypoplasia, microcephaly, encephalomalacia, cavitary lesions, astrocytosis, polymicrogyria, and severe neuronal loss. Cranial ultrasonography failed to document the diverse pathologic lesions that were later noted on postmortem examination. Ten infants survived the neonatal period, but 6 were neurologically abnormal at the time of discharge. Infants with NIHF are at risk for antepartum brain injury, and electroencephalographic abnormalities reflect in part a fetal brain disorder. A prospective clinical study is needed to fully assess the prevalence, incidence, spectrum of central nervous system involvement, contribution of intrapartum and neonatal stress, and long-term outcome in surviving infants with NIHF. PMID- 7986288 TI - Natural history and outcome of neonatal hypocalcemic and hypomagnesemic seizures. AB - The clinical characteristics and neurologic outcome of 15 newborn infants with seizures due to hypocalcemia and hypomagnesemia have been studied with careful exclusion of those patients who had other possible etiologies for seizures. Associated diagnoses included severe congenital heart disease in 7 of 15 (47%) patients. Possible causes for this association with congenital heart disease include a forme fruste of DiGeorge syndrome, hypocalcemia and hypomagnesemia due to critical illness, and subtle embolic cerebral ischemia. In contrast with previous studies, no abnormalities of formula milk feeding were observed. Five patients (36%) died of causes unrelated to seizures. Follow-up in 8 of 9 patients who had no cerebral insults other than neonatal seizures at a mean age of 57.8 +/ 10.5 months found neurologic abnormalities in 2 (22%), both with an endocrine etiology for hypocalcemia. We conclude that infants with severe congenital heart disease should be investigated for hypocalcemia and hypomagnesemia. Previous observations of a universally favorable neurologic outcome in newborns with hypocalcemic or hypomagnesemic seizures may be valid for those who have a nutritional etiology for the metabolic disturbance but are less relevant to the current population in whom hypocalcemia or hypomagnesemia due to errors in formula milk feeding is seldom observed. In this group, neurologic prognosis may be more related to associated medical conditions. PMID- 7986289 TI - Clinical significance of periodic lateralized epileptiform discharges in children with relation to level of consciousness. AB - Six children with acute cerebral insult, ranging in age from 3 days to 8 years, revealed periodic lateralized epileptiform discharges in their electroencephalographic recordings. Their etiologic factors were cerebral infarction, intracranial bleeding, purulent meningitis, acute infantile hemiplegia, and encephalitis. Each patient exhibited a different type of convulsive seizure. Computer tomography or magnetic resonance imaging revealed diffuse lesions covering the cerebral cortex and subcortical white matter in 2 patients, a lesion of the subcortical white matter in 1 patient, a linear lesion in the cortex and along the borderline between the cortex and the subcortical white matter in 1 patient, and localized lesions in the cortex and basal ganglia in 1 patient. There were findings indicating the disconnection of the cerebral cortex with deeper structures in 3 patients. The appearance rate of periodic lateralized epileptiform discharges increased at levels of consciousness from 5 to 7 on a pediatric modification of the Glasgow Coma Scale. At levels of consciousness from 8 to 14 and below 4, the rate was very low. PMID- 7986290 TI - Relationship between the parachute reactions and standing and walking in normal infants. AB - Assumption of the vertical position and independent walking are potentially hazardous motor milestones in the developing infant. It has been presumed that the parachute reactions evolved to protect infants from injury during this developmental stage. To determine the relationship between the appearance of the upper and lower parachute reactions and the developmental milestones of unsupported standing and independent walking, 190 normal infants were prospectively studied. The upper parachute reaction was found to precede the lower by less than a month (mean age of appearance: 8.9 and 9.2 months, respectively). More than one-half of the cohort achieved standing without either the upper (49%) or lower parachute reaction (57%); however, no independent walking occurred without the upper parachute reaction, and only 2 of 190 infants (1%) walked independently without the lower parachute reaction. Onset of walking occurred about 4 months after the appearance of the upper parachute reaction. The significance of these findings is discussed. PMID- 7986291 TI - Childhood neurologic disorders and Lyme disease during pregnancy. AB - To determine the prevalence of clinically significant nervous system disease attributable to transplacental transmission of Borrelia burgdorferi, we surveyed neurologists in areas of the United States in which Lyme disease is endemic (i.e., Massachusetts, Rhode Island, Connecticut, New York, New Jersey, Wisconsin, and Minnesota). Overall, 162 of the 176 (92%) pediatric neurologists contacted responded to the survey with a range of 90-100% in the different geographic areas. One pediatric neurologist was following 3 children who were labeled as having "congenital Lyme disease," but none of the 3 met our case definition. None of the other pediatric neurologists surveyed had ever seen a child whose mother had been diagnosed as having Lyme disease during pregnancy. Similarly, none of the 37 adult neurologists in Connecticut surveyed had ever seen a child whose mother had been diagnosed as having had Lyme disease during pregnancy. We conclude that congenital neuroborreliosis is either not occurring or is occurring at an extremely low rate in areas endemic for Lyme disease. PMID- 7986292 TI - Gallium nitrate delays the progression of microscopic disease in a human medulloblastoma murine model. AB - The goal of adjuvant chemotherapy is to treat postoperative microscopic disease in the hope of preventing tumor recurrence and/or metastasis. Since the introduction of chemotherapeutic agents, the disease-free survival of children with medulloblastoma has improved only modestly. Therefore, there is a need to develop and investigate new chemotherapeutic agents for this malignancy. Gallium nitrate has demonstrated significant antineoplastic activity toward human medulloblastoma in vitro and in vivo and may prove to be an optimal chemotherapeutic agent in treating medulloblastoma microscopic disease. The present study consisted of injecting medulloblastoma Daoy intradermally into both flanks of nude mice. A 15-day 50-mg/kg/day regimen was implemented the day after tumor inoculation. All treated and control mice received saline hyperhydration during the treatment period. The interval between tumor cell inoculation and first measurable tumor detection, tumor occurrence, growth rate, and size were recorded. Results indicated that gallium nitrate significantly prolonged the interval between tumor cell inoculation and measurable tumor detection. PMID- 7986293 TI - Focal spasms in clusters, focal delayed myelination, and hypsarrhythmia: unusual variant of West syndrome. AB - We report a patient who began to have clusters of seizures characterized by brief elevation of the right arm at 6 months of age. An interictal electroencephalogram (EEG) at 7 months revealed hypsarrhythmia without definite asymmetry. Simultaneous EEG and video recording disclosed that these focal spasms were associated with fast wave bursts superimposed on slow waves most markedly in the left centro-midtemporal region. The patient became seizure-free after synthetic ACTH therapy. The patient is developmentally normal at 3 years 5 months, but magnetic resonance imaging studies revealed findings suggestive of delayed myelination in the left frontal region. This patient is considered to have had an unusual variant of West syndrome associated with focal delayed myelination. PMID- 7986294 TI - Rett variants: a suggested model for inclusion criteria. AB - A model for the clinical delineation of atypical cases of Rett syndrome is presented. It is based on the presence, at age > or = 10 years, of combined clusters of at least 3 of 6 primary criteria and at least 5 of 11 supportive manifestations appearing through childhood with advancing age. The model was applied to 16 mentally retarded females, aged 11-47 years (median: 23) who were considered to manifest atypical variants of the syndrome (8 formes frustes, 6 late regression, 2 congenital variants). Two of the 16 patients had an early seizure history as the initial abnormality. In parallel, the number of supportive manifestations in a series of 41 females over 10 years of age with classic Rett syndrome are given. The differentiating power was tested on 8 patients with a chromosome-verified Angelman syndrome. It is concluded that the model applied here has the capacity to identify and distinguish Rett syndrome variants of different types, to sift out other developmental disorders in routine clinical work, and to have potential as a useful research tool. PMID- 7986295 TI - Acute disseminated encephalomyelitis presenting as a neurodegenerative disease in infancy. AB - An infant with acute demyelinating encephalomyelitis resulting from California virus infection presented with a neurodegenerative clinical picture. The clinical course was complicated by infantile spasms which responded to treatment with corticotropin. Acute demyelinating encephalomyelitis should be included in the diagnostic evaluation of patients who present with subacute regression of developmental milestones. PMID- 7986297 TI - Monozygous twin with polymicrogyria and normal co-twin. AB - Monozygous twinning has been associated with brain lesions such as holoprosencephaly, hydranencephaly, multicystic encephalomalacia, and porencephaly. Polymicrogyria is rare but has been reported in autopsied cases. We present a monozygotic twin with complicating twin-twin transfusion syndrome, the donor exhibiting normal psychomotor development and the recipient psychomotor delay associated with the brain anomaly, polymicrogyria. The brain anomaly might be due to blood pressure instability or a circulatory disturbance resulting from increased coagulability due to polycythemia. PMID- 7986296 TI - Aplastic anemia following therapy for absence seizures with ethosuximide. AB - We describe a case of aplastic anemia in an 8-year-old girl which was diagnosed 8 months after initiation of ethosuximide as treatment for absence seizures. Blood counts had been previously monitored and were normal. The patient successfully underwent allogeneic bone marrow transplantation. Only 8 cases of ethosuximide associated aplastic anemia have been reported, and in only one of these reports, was ethosuximide used as a single antiepileptic agent. This rare, but potentially fatal complication of ethosuximide raises the question of whether routine monitoring of blood counts during ethosuximide therapy is useful and should be undertaken. PMID- 7986298 TI - Self-mutilation in a patient with mucolipidosis III. AB - An 8-year-old girl with mucolipidosis III had self-mutilation of the distal phalanges of the second and third digits of her hands. She had neurophysiologic evidence of carpal tunnel syndrome, and consequent insensitivity to pain, which could explain the self-mutilation. Self-mutilation has not been previously described in lysosomal diseases in which carpal tunnel syndrome is frequently observed. PMID- 7986299 TI - Benign paroxysmal torticollis. PMID- 7986300 TI - Non-Insulin-Dependent Diabetes Mellitus and Atherosclerosis: a Lipoprotein Perspective. Symposium proceedings. London, United Kingdom, 3-4 December 1993. PMID- 7986301 TI - Non-insulin-dependent diabetes mellitus and atherosclerosis: a lipoprotein perspective. PMID- 7986302 TI - Efficacy and safety of fluvastatin in hyperlipidaemic patients with non-insulin dependent diabetes mellitus. AB - In this preliminary report of a 20-week trial, 66 patients with non-insulin dependent diabetes mellitus (NIDDM) and hyperlipidaemia who remained eligible after an 8-week dietary stabilization phase were randomly allocated to receive 20 mg of fluvastatin or placebo once daily for 6 weeks. Fluvastatin was subsequently increased to 20 mg twice daily and administered according to the same schedule, versus placebo, for a further 6 weeks. Both dosages of fluvastatin substantially improved serum lipid profiles compared with baseline and placebo. Both dosages of fluvastatin significantly reduced low-density- and very-low-density-lipoprotein (LDL, VLDL), cholesterol and triglyceride (TG) compared with placebo, and both dosages significantly elevated high-density-lipoprotein (HDL) cholesterol. The ratio of LDL to HDL was also significantly decreased. Amongst the 58 patients who completed the study, there was no evidence either of myopathy or of hepatotoxicity; mean creatine kinase values remained stable in the fluvastatin arm. Fasting glucose, glycosylated haemoglobin, and fructosamine levels were not markedly affected by active treatment. No serious adverse events attributable to the drug were reported. In conclusion, both dosages of fluvastatin appear to be effective and safe in the management of hyperlipidaemia in this outpatient, maturity-onset, diabetic population. PMID- 7986303 TI - Syndrome X: 6 years later. AB - Resistance to insulin-stimulated glucose uptake is a common phenomenon, occurring in approximately 25% of the population at large, and is associated with a number of conditions known to be risk factors for coronary heart disease (CHD). These include hyperinsulinaemia, abnormal glucose tolerance, non-insulin-dependent diabetes mellitus, increased plasma triglyceride and decreased high-density lipoprotein cholesterol concentrations, smaller, denser low-density-lipoprotein particles, hypertension, and abnormalities of fibrinolysis. These abnormalities frequently occur in a cluster within individuals. Understanding the basis of these changes, as well as the interrelationships between them, will contribute substantially to future studies of the causes of CHD, and ultimately form the basis for the clinical management of insulin-resistant individuals. PMID- 7986304 TI - Hyperinsulinaemia and hypertriglyceridaemia. AB - Hyperinsulinaemia and hypertriglyceridaemia are frequently associated. This may be as a part of the syndrome of insulin resistance or in diabetes, particularly non-insulin-dependent diabetes (NIDDM). The importance of this association lies in the facts that atherosclerosis is the most frequent complication of diabetes, that hypertriglyceridaemia is a risk factor for coronary artery disease in diabetic populations and that hyperinsulinaemia also appears to be a risk factor for atherosclerosis. Hypertriglyceridaemia, even without obesity, is associated with resistance to insulin. This can result in compensatory hyperinsulinaemia. Chronic hyperinsulinaemia has been shown to increase the production of triglyceride (TG)-rich lipoproteins. The vast majority of particles in the TG rich lipoprotein spectrum are in the intermediate-density-lipoprotein (IDL) range. Furthermore, increased levels of TG result primarily from increased numbers of these particles, rather than from increased particle size. This is important because, at least in nondiabetic individuals, increased levels of IDL are associated with increased atherosclerosis. Thus, there may be a vicious cycle of insulin resistance, hyperinsulinaemia, hypertriglyceridaemia and atherosclerosis. We have found that by reducing plasma TG levels alone, one can increase sensitivity to insulin and break this cycle. PMID- 7986305 TI - Dyslipoproteinaemia in manifest diabetes. AB - The prevalence of hypercholesterolaemia is similar in non-insulin-dependent diabetic (NIDDM) patients and in non-diabetic subjects. The prevalence of hypertriglyceridaemia and of low high-density-lipoprotein (HDL) cholesterol is roughly double the norm in NIDDM, but the exact prevalence varies greatly from study to study. Obesity and a familial form of hypertriglyceridaemia (conditions that may alter plasma lipoprotein levels) are frequently observed in NIDDM patients. In carefully controlled NIDDM patients without concomitant primary hyperlipoproteinaemia, body weight may be more important than glycaemic control or the type of treatment plan adopted in determining lipoprotein levels. Hypertriglyceridaemia in NIDDM is a result of both increased very-low-density lipoprotein (VLDL) synthesis and impaired VLDL catabolism. Whilst low-density lipoprotein (LDL) levels are normal, the LDL synthesis and removal rates may be increased. Low high-density-lipoprotein (HDL) levels may be due to increased catabolism. In addition to quantitative changes in plasma lipids and lipoproteins. NIDDM patients demonstrate qualitative lipoprotein alterations. The size and density of LDL particles in NIDDM patients are greatly affected by triglyceride levels. Smaller, denser LDL particles have been observed in hypertriglyceridaemic subjects. Glycosylation of apolipoproteins may alter the metabolic properties of lipoproteins. Glycosylated and small, dense LDL have an increased susceptibility to oxidation. PMID- 7986307 TI - The contribution of lipids to coronary heart disease in diabetes mellitus. AB - Cardiovascular disease is two to three times more common in diabetic patients than in the non-diabetic population. Although risk factors that affect the general population such as age, cigarette smoking, hypertension, obesity and hypercholesterolaemia also affect diabetic subjects, the increased prevalence of hypertension and obesity in non-insulin-dependent diabetes mellitus (NIDDM) only partially explains the increased morbidity and mortality from coronary heart disease (CHD). Other factors must therefore be considered in this group of patients. Triglyceride concentrations, particularly post-prandial levels, may be important. Diabetic subjects have increased very-low-density-lipoprotein (VLDL), increased intermediate-density-lipoprotein (IDL) and low high-density-lipoprotein (HDL) concentrations, and differences in lipoprotein composition may partly explain increased atherogenesis. Although LDL levels of diabetic patients are not different from those of control subjects. LDL particles are potentially atherogenic as they are smaller, more dense and prone to oxidative modification. NIDDM subjects also have altered apolipoprotein concentrations, including increased apoB, apoC-III, and decreased apoA-I; in addition, apoE-2 may be over represented in diabetic populations. Thus, apart from the traditional risk factors, there are several lipoprotein compositional abnormalities that may contribute to the increased prevalence of CHD in diabetes. PMID- 7986306 TI - Triglyceride-rich lipoproteins and atherosclerosis: pathophysiological considerations. AB - The potential role of triglyceride-rich lipoproteins (TGRLP) in the pathogenesis of atherosclerosis is briefly reviewed. Structural attributes of TGRLP are related to functional cellular interactions relative to their ability to interact with macrophage receptors and produce foam cells. Unlike low-density lipoproteins (LDL), no prior modification (oxidation or acylation) is necessary with TGRLP from certain hypertriglyceridaemic subjects and certain postprandial-TGRLP before rapid, receptor-mediated lipid engorgement occurs. In addition, arguments are examined that challenge the differing views that this lipoprotein class is not important in atherogenesis. PMID- 7986308 TI - Diabetic dyslipidaemia: treatment implications. AB - Diabetes is associated with increased morbidity and mortality from cardiovascular disease in the absence of the major risk factors--cigarette smoking, hypertension and serum cholesterol concentration. When these risk factors are present, the attributable risk to each factor alone and to the combination of risk factors is higher in diabetic than in nondiabetic subjects. Thus, stringent measures to correct risk factors for cardiovascular disease have been advocated in diabetic patients. In addition to hypercholesterolaemia, other lipid and lipoprotein abnormalities collectively referred to as diabetic dyslipidaemia probably contribute to vascular risk. Hypertriglyceridaemia, often associated with low high-density-lipoprotein cholesterol, is common in NIDDM patients and is associated with insulin resistance. Recent information in diabetic patients, pointing to the association of hypertriglyceridaemia with accumulation of remnant particles and alterations in low-density-lipoprotein subfractions, helps to explain the strong relationship between hypertriglyceridaemia and vascular risk in these individuals. Although there are as yet no intervention trials with lipid lowering diets or drugs in diabetic patients to judge the impact on vascular disease, national and international bodies have furnished guidelines for the identification and treatment of lipid disorders in diabetes in the hope of reducing the huge toll of vascular disease in these patients. PMID- 7986309 TI - The epidemiology of coronary heart disease in glucose-intolerant and diabetic subjects. AB - Diabetes mellitus is usually recognized as a major risk factor for coronary heart disease (CHD) morbidity and mortality. As chronic hyperglycaemia defines diabetes mellitus, it is logical to think that hyperglycaemia itself is related to these complications. But, in diabetic patients, there appears to be no relation between CHD and the specific characteristics of diabetes, namely the duration of the disease and the level of blood glucose. Moreover, in the UGDP trial, the group of patients with the best-controlled glycaemia failed to demonstrate a reduction in CHD death, in comparison with the group with poor blood-glucose control. These results are reinforced by the data from 15 prospective studies, which failed to demonstrate a homogeneous and significant increase in CHD risk with asymptomatic hyperglycaemia. Coronary heart disease mortality depends on a constellation of risk factors which are interrelated to some extent; one of the risk factors, namely blood glucose, is not an independent risk factor, nor is diabetes mellitus. In patients with abnormal glucose tolerance, the factors contributing to CHD risk are hypertriglyceridaemia and also a central fat distribution. This central fat distribution could explain the low CHD risk in nondiabetic women, which contrasts with the high risk in diabetic women, who are characterized by central adiposity, as are diabetic men. Bjorntorp hypothesized that intra abdominal fat, which has an exceedingly sensitive lipid mobilization capacity, could play a key role in the development of the cluster of metabolic abnormalities that are present in the plurimetabolic syndrome. Hyperglycaemia, one of the anomalies of the syndrome, could be an 'innocent bystander' rather than a 'partner in crime', in the manifestations of CHD. PMID- 7986310 TI - Genetic predisposition to hyperlipidaemia in diabetes: the end of the beginning? AB - Diabetes mellitus leads to disturbances in lipoprotein homeostasis particularly when there is poor glycaemic control. The resulting abnormalities in concentration and composition of the circulating lipoproteins are modified by inherited variation in the genes coding for apolipoproteins, for the lipoprotein processing enzymes, and possibly for lipoprotein receptors. Thus, poorly controlled diabetes provides an opportunity to observe the phenotypic effects of recessive mutant alleles that would otherwise be silent. This phenomenon should be considered when one attempts to understand the pathogenesis of variant phenotypes, ones differing from those typical of diabetes mellitus alone. Our understanding of how genetic variation modulates the expression of hyperlipidaemia in diabetes is still rudimentary--it now seems probable that many other genetic conditions affecting lipoprotein metabolism in diabetes will eventually be brought to light. PMID- 7986311 TI - Polymorphisms of the lipoprotein lipase gene and premature atherosclerosis. AB - Allelic frequencies of polymorphic variants at the lipoprotein lipase gene locus have been measured in subjects with premature coronary artery disease and dyslipidaemia. One of the polymorphic variants involves a termination codon in exon 9 that produces a truncated protein whose Michaelis constants for triolein or chylomicra are identical to the native enzyme but whose Vmax for both substrates may be increased. The other informative polymorphism is a HindIII site in intron 8 that shows marked assymetric allelic distribution in subjects with hypertriglyceridaemia/low HDL syndrome and in subjects with premature coronary artery disease. It is hoped that the marker may lead to the identification of an aetiological mutation in its vicinity to account for these disease associations. PMID- 7986312 TI - Modified lipoproteins in diabetes. AB - The mechanisms by which diabetes leads to various manifestations of tissue damage are not yet fully understood; however, different recent studies suggest that some of them may be mediated by modified lipoproteins, although other lipid abnormalities also have been described in diabetes patients. Principally, the modification consists of an oxidation of the lipoprotein particle [mainly low density lipoprotein (LDL)]. The oxidized LDL is then rapidly internalized by macrophages, converting them to cholesterol-loaded foam cells. In diabetic patients, oxidation occurs through two pathways: enzymatic (vascular inflammation) and nonenzymatic (polyunsaturated fatty acids) that can be blocked either by acetyl salicylic acid or by antioxidants. Moreover, in diabetes patients, higher glucose levels can also lead to a direct (stimulated by metals) or an indirect (by generation of glycosylated proteins) generation of free radicals, which will also damage proteins and collagen in particular. Clinically, lipid peroxide concentrations are higher in diabetic than in nondiabetic subjects, particularly in patients with vascular complications and with high triglyceride levels. These lipid peroxide levels can be decreased by antioxidants, whose concentrations are lower in diabetic patients. Preliminary data also indicate that HMG CoA reductase inhibitors can decrease lipid peroxide concentrations. PMID- 7986313 TI - Interactions amongst insulin, lipoproteins and haemostatic function relevant to coronary heart disease. AB - Interest has increased considerably in the past few years in the possible interactions amongst insulin, plasma lipoproteins and several components of the haemostatic system. There is now consistent epidemiological, clinical and experimental evidence that hypertriglyceridaemia, in particular, may represent a procoagulant state involving derangements of both blood coagulation and fibrinolysis. Imbalance in the haemostatic system secondary to increased clotting activity, impaired fibrinolytic function, or a combination thereof, should influence the growth and final size of evolving thrombi and predispose to arterial occlusion. This might be of particular significance in the coronary circulation, where a hypercoagulable state is likely to promote thrombosis at the site of a suddenly ruptured atherosclerotic plaque. In addition, there is accumulating experimental evidence that the haemostatic system plays a part in plaque formation and plaque growth. Basic research on the link between haemostasis and atherosclerosis should be given high priority, because modulation of haemostatic function will probably be a potent complementary approach to the prevention of coronary heart disease. PMID- 7986314 TI - Dyslipidaemia and cardiovascular disease in non-insulin-dependent diabetic patient with and without diabetic nephropathy. AB - In 370 non-insulin-dependent diabetic (NIDDM) patients less than 66 years of age, we found the prevalence of albuminuria (> 300 mg 24 h-1) to be 13.8%. Males had a higher prevalence than females (19 vs. 5%). A kidney biopsy was performed in 35 patients. The biopsy revealed diabetic glomerulosclerosis in 77% of the cases and a variety of non-diabetic glomerulopathies in the remaining 23%. Fifty-six per cent of the patients with diabetic glomerulosclerosis had diabetic retinopathy, whereas none of the patients with non-diabetic glomerulopathies had signs of retinopathy. The presence of diabetic retinopathy strongly suggests that diabetic glomerulosclerosis is the cause of albuminuria. During a 5-year (range 1-7 years) prospective study, the course of kidney function was followed in 26 NIDDM patients with diabetic glomerulosclerosis. The glomerular filtration rate declined, and elevated systolic blood pressure was positively correlated to the rate of decline. The frequency of diabetic complications increased with increasing levels of urinary albumin excretion. In a cross-sectional study of 549 NIDDM patients, the prevalence of proliferative retinopathy was 2, 5 and 12%, the prevalence of hypertension 46, 68 and 85%, and the prevalence of ischaemic heart disease 22, 26 and 46% in normo-, micro-, and macroalbuminuria, respectively. The mortality from cardiovascular disease is increased ninefold in NIDDM patients with macroalbuminuria compared to the non-diabetic background population. The presence of the well-established risk factors cannot account for this finding alone.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7986315 TI - Effect of fluvastatin on plasma apolipoprotein-B-containing particles, including lipoprotein(a). European Fluvastatin Study Group. AB - Epidemiological studies have demonstrated an association between apolipoprotein (apo)-B containing particles [lipoprotein (Lp) (a), LpE:B; LpC-III:B] and coronary heart disease (CHD). The effect of fluvastatin, a novel competitive inhibitor of HMG-CoA reductase, on these plasma lipoprotein levels was studied in patients with hypercholesterolaemia after 14 weeks of standard dietary therapy. The results of a placebo-controlled, dose-response study and of the combined data of the European double-blind, controlled studies on the effect of fluvastatin are presented. The patients were selected according to the following criteria of inclusion: plasma low-density-lipoprotein (LDL) cholesterol levels > 160 mg dL-1 and premature CHD and/or two associated risk factors, or LDL cholesterol > 190 mg dL-1 and no CHD, plus triglycerides < 300 mg dL-1. All measurements were performed at the Pasteur Institute Central Laboratory. Lp(a), LpE:B and LpC-III:B particles were measured by double-site ELISA. In the placebo-controlled, dose response study, 429 subjects were randomly assigned to one of the following treatment groups: placebo, fluvastatin 2.5 mg q.p.m., 5 mg q.p.m., 10 mg q.p.m. and 20 mg q.p.m. Treatment with fluvastatin for 6 weeks was associated with a dose-dependent reduction of LDL cholesterol, apoB, LpE:B and LpCIII:B levels. In addition, treatment with fluvastatin 5 mg and 20 mg q.p.m. was associated with a significant reduction in median Lp(a) concentrations (3.2%, P < 0.05 and 6.4%, P < 0.05 respectively.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7986316 TI - A comparison of the diets of Siberian Chukotka and Alaska Native adults and recommendations for improved nutrition, a survey of selected previous studies. AB - Diet plays an important role in the development of common diseases among Northern indigenous people, i.e. heart disease, cancer, diabetes and iron deficiency. Their unique diets may contribute to or protect from these diseases. The diets consumed by Siberian Chukotka Natives (Russia) and Alaska Natives (United States) during the 1980's are described. Traditional foods still play a major role, although the extent of their use varies. Alaska Natives' diets are more "western" than are those of Chukotka Natives. They consumed a greater proportion of kilocalories as carbohydrates and fat than Chukotka Natives. Coastal Chukotka Natives had lower average serum LDL-cholesterol and higher HDL-cholesterol levels than tundra Chukotka Natives, despite their high fat and kilocalorie intakes. Dietary recommendations common to both groups are presented which encourage the use of traditional foods as the foundation of the diet supplemented with western type foods of appropriate quality and quantity. PMID- 7986317 TI - The relation of sleep-wake patterns to seasonal depressive behavior. AB - A sample of 1644 adults in Alaska, Chukotka, Yakutiya, Western Siberia and Turkmenistan were surveyed to examine the relationship between seasonal depressive behavior and sleep-wake patterns. Interviews included items derived from the Seasonal Pattern Assessment Questionnaire, a 20 item general depression scale, and a 40 item sleep-wake questionnaire designed to assess the underlying mechanisms which regulate the cycles of sleep and wakefulness. Results show that subjects who suffer from seasonal depressive behavior, at latitudes ranging from 38-66 degrees North, are characterized by a sleep-wake pattern including 1) difficulty waking in the morning, 2) a low capacity to be awake at unusual times (out of sync with normal circadian patterns) and 3) a lower quality of nighttime sleep. Subjects with high levels of general depression suffer many of the same sleep problems, but this is not due to the measured association between seasonality and other depression. Disturbances in sleep-wake patterns may help to expand our understanding of the pathogenesis of seasonal depressive behavior, but further research to differentiate it from general depression is required. PMID- 7986318 TI - Diurnal and seasonal variations of melatonin and serotonin in women with seasonal affective disorder. AB - In winters 1990-1991 and 1991-1992 women with and without seasonal affective disorder, winter type, were treated by light at 2500 lux either in the morning (0800h-1000h) or afternoon (1600h-1800h). In winter before light treatment, melatonin levels in serum in daytime (1200h and 1600h) were higher in patients compared to controls (p < 0.05). This difference disappeared in the summer or after light treatment in the winter. Also, light treatment and change in season resulted in a phase advance shift of melatonin rhythm in patients. The decline in melatonin levels correlated with the decline in specific SAD symptoms of hyperphagia and carbohydrate craving. In winter, neither patients nor controls showed significant diurnal variations in levels of whole blood serotonin. In both patients and controls, levels of serotonin were higher in summer as compared with winter, especially at 2000h. Our data suggest that elevated daytime melatonin can be a state marker of winter depression, and that seasonal change of photoperiod may also affect the circadian amplitude and daytime levels of blood serotonin. PMID- 7986319 TI - Evening melatonin in January after changes in hours of habitual exercise during fall among youths living in the subarctic. AB - Secretion of the hormone melatonin shows a circadian rhythm and is inhibited by light. Light therapy with phase shifting of the melatonin rhythm has been used as treatment of sleeping problems and seasonal affective disorders (SAD). Exercise has also been shown to suppress the melatonin secretion. In order to investigate the effect of increased level of habitual physical activity upon melatonin secretion in areas with extreme short days and high level of midwinter insomnia, 18 high school students participated in this study. Their habitual physical activity throughout two consecutive falls were recorded. The following January, blood samples were taken for melatonin analyses from 1530h to 2300h. After the fall with highest habitual activity level, the plasma melatonin showed significantly decreased values at all sampling times compared to values after lowest level of activity. The relative increase in melatonin level at 2300h, however, tended to be of a greater magnitude after the fall with highest activity compared to the fall with lowest activity (p = .094). A change in habitual level of activity should be thought of as a possible help for treating midwinter insomnia and SAD. PMID- 7986320 TI - Goitre prevalence in indigenous population of Evenkia. AB - Representatives of indigenous northern peoples (the Evenks and the Kets) living in a large Siberian territory named Evenkia were studied. There were children 6 14 years of age and adults aged 18-45 years. Thyroid volumes were determined by ultrasound. Iodine excretion was estimated. Normal thyroid volumes were found in 27.5% of the children. A high prevalence of goitre was detected in the adults. 55.4% of the women and 29.1% of the men had thyroid volumes above normal upper limits. Nodular goitres were found in 10.8% of the adults. 58.8% of the subjects had urinary iodine excretion below 10 micrograms/dl. Data show that the territory of Evenkia, settled by northern aborigines, is iodine deficient. The usage of the iodinated salt is ineffective. The preservation of the iodine content in salt remains the main problem in this area. In addition, some other goitrogenic agents may contribute to the high goitre prevalence in the indigenous population in Evenkia. PMID- 7986321 TI - [Malignancy of tumors of the minor salivary glands]. PMID- 7986322 TI - [Sialochemical studies of isolated secretions of the major salivary glands of the head]. AB - The sialochemical parameters total protein, immunoglobulin A, lysozyme, amylase, sodium, potassium, calcium as well as flow rate were estimated in parotid saliva (PS) and submandibular saliva (SMS) in the course of differential diagnostics of salivary gland diseases. In addition to this the quantitative polyacrylamide gel electrophoresis based on 80 PS and 80 SMS normal secretions was performed. Sialochemistry was performed on parotid adenomas (29), carcinomas (9); sialadenosis (8); acute (8) and chronic (13) sialadenitis; dental caries (12 PS and 12 SMS); cystic fibrosis (21 PS and 12 SMS); diabetes mellitus (13 PS and 13 SMS); and hyperthyroilism (9 PS and 9 SMS). Our sialochemical analysis does not allow to distinguish between benign and malignant parotid neoplasms. The significant decrease of sodium in sialadenosis and increase of sodium and total protein in sialadenitis as well as interesting results in cystic fibrosis, diabetes mellitus and dental caries, are emphasised. PMID- 7986323 TI - [Site and epidemiology of mucoepidermoid carcinoma. Analysis of 327 cases]. AB - The salivary gland registry of the University of Hamburg (1965-1992) comprises a total of 327 mucoepidermoid carcinomas (MEC). MEC occur between the age of 5 and 96 years, most frequently in the sixth and seventh decade of life. The average age lies below 50 years (48.9 years). There is a slight predisposition of females (56.3%). Nearly 60% of all MEC care localised in the major salivary glands. The parotid gland is the most frequent localisation (53.5%) followed by the palate (17.4%). MEC are less frequent in the submandibular and sublingual glands, such as the minor salivary glands of the oropharynx and the cavity of the mouth. 53.2% of all MEC's can be classified as highly differentiated, the remaining 46.8% as poorly differentiated. MEC's of the palate are predominantly highly differentiated (72.0%). Among the variants of MEC, cystic (25.4%), clear cell (11.0%) and oncocytic (0.6%) tumours can be observed. MEC's of the clear cell type tend to originate from minor salivary glands (69.5%). MEC of childhood and adolescence (8.6%) are preferably seen in the parotid gland (46.4%) and the palate (39.3%). Up to the 20th year of life, cystic tumours and tumours of the clear cell type are comparatively more frequent. PMID- 7986324 TI - [Histology of mucoepidermoid carcinoma. Analysis of 327 cases]. AB - The mucoepidermoid carcinomas of the salivary glands (MEC) show histologically a wide spectrum of differentiation from solid epidermoid tumours to cystic mucous filled tumours. Epidermoid cells, mucous cells and intermediate cells are the main cellular components. Besides clear cell (11.0%) and oncocytic (0.6%) variants and "cystic" (25.4%) tumours can be observed. According to the per cent of mucous cells and cystic spaces of the total tumour mass different degrees of histomorphologic differentiation can be distinguished. Therefore highly differentiated MEC (53.2%) with more than 50% mucous cells and cystic spaces, respectively low-differentiated MEC (46.8%) showing less than 50% mucous cells and cystic spaces can be subclassified. In respect of the therapeutic proceeding it should be recognized that the histopathological subclassification of MEC of the salivary glands (7) is based on morphological criteria only. It may not be equalized with a grading of malignancy since even highly differentiated MEC can grow infiltratively, sometimes osseo-destructively, to recur locally and to metastasize predominantly into the regional lymph nodes. Consequently the histopathological subclassification of MEC does not allow certain prognosis in individual cases. PMID- 7986325 TI - [Pathogenetic and therapeutic aspects of contact granuloma]. AB - Contact ulcer and granuloma is an etiologically multifactorial chronic inflammatory disease of the larynx. Besides mechanical laryngeal factors, gastrointestinal and psychosomatic aspects of pathogenesis have been suggested. 51 patients suffering from contact ulcer or granuloma underwent laryngologic and phoniatric examination. In addition, a questionnaire asking for symptoms and habits (smoking, alcohol) was completed by each patient. Subsequent to completing the treatment course, the patients were re-examined. Each patient was examined several times and the success of 6 therapeutic strategies was compared. 49 patients were male and almost 70% complained of private or professional stress. Since only 8% were smokers, smoking habits do not play a pathogenetic role. Drinking habits are also not a significant factor. A striking therapeutic result observed by us was complete remission in more than 80% of patients who had received an acid-inhibiting agent as monotherapy. The remission was higher in this group than in patients treated by logopedic therapy. In case of carcinophobia or if cancer could not be excluded by laryngoscopy and stroboscopy, granulomas were removed surgically. More than 90% of these patients suffered from recurrence unless voice therapy was directly performed. On the other hand, antacid therapy yielded excellent results in patients suffering from recurrent granuloma or ulcer after surgery. We conclude that peptic diseases of stomach and oesophagus play an important role in the pathogenesis of contact ulcer and granuloma and recommend routine interviews and internal examination of patients. Antacid therapy should be firmly installed in the therapeutic strategy against contact ulcer. PMID- 7986326 TI - [Applications of the "Speech Viewer II" in voice training in vocal cord paralysis]. AB - Referring to traditional therapeutical concepts of vocal fold paralysis a microphone-controlled computer programme was used for voice treatment in 13 patients with unilateral vocal fold paralysis. 6 of these patients were female, 7 were male. The age ranged from 18 to 72 years (mean: 50 years). The etiology of the paralysis was distributed as follows: post strumectomy (4 cases), post operation of the aortic arch (3 cases), post mediastinoscopy (1 case), post operation of the cervical vertebrae (1 case). 2 cases are not decided yet, 2 are probably idiopathic. The vocal fold dysfunction lasted between 24 hours and 8 years before our first examination, less than 4 weeks in 11 cases. With 1 exception (intermediate) the vocal fold position was classified as paramedian. 8 patients suffered from left, and 5 patients from right vocal fold paralysis. The voice treatment took place with a microphone-controlled speech viewer including an audio capture and playback adapter. 7 of the 15 training modules of the computer programme were chosen to be useful for voice training. Those modules can be differentiated in physical-technical modules showing voice spectra or pitch scales and in object-related modules showing images such as landscapes, animals and others. These programme-specific modules (monitor exercises) were primarily built to train the following voice qualities separately: loudness, pitch, voicing, voice onset, fundamental frequency, sustained phonation etc. Modifying certain therapeutic instructions (see Tables 1 and 2) the monitor exercises were used to improve the coordination of different voice parameters, thus resembling physiological speech.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7986327 TI - [Secondary ambulatory voice prosthesis implantation with the argon laser using local anesthesia]. AB - An alternative technique for secondary tracheo-esophageal puncture and voice prosthesis implantation in topical anesthesia on an outpatient basis was developed. With argon laser beam passed through a glass fibre in the instrument channel of a flexible endoscope a secondary puncture of the tracheo-esophageal wall is obtained. A voice prosthesis is fitted subsequently, so that the whole operation is performed in one session in about 30 minutes. We generally administer 7.5 mg Midazolam orally for light sedation; antibiotics are not required. This method expands the possibility of voice prosthesis fitting in patients who are not considered or willing to have general anesthesia for various reasons. In 33 cases we did not see any complication. In two cases the tracheal wall was too tight due to radiation therapy, so that an operation had to be performed later on in general anesthesia. In one case technical problems led to an operation in local anesthesia in two steps. In all cases the patients did not complain of any considerable discomfort. PMID- 7986328 TI - [Voice rehabilitation from the viewpoint of the laryngectomized patient. Results of a patient survey]. AB - 105 of 292 patients who had been laryngectomised at the Zentralkrankenhaus Bremen, between 1975 and 1990, were asked retrospectively by questionnaires concerning the state of their voice rehabilitation. 66.6% of them had learnt oesophageal speech, 36.2% used an external vibrator, and 9.4% a voice prosthesis (since 1985). 82.8% used only one kind of substitute (non-laryngeal) speech. If patients used more than one non-laryngeal speech pattern, the most frequent combination was oesophageal speech and an external vibrator. The most rapid voice rehabilitation was achieved by patients using a voice prosthesis (71.3% within six weeks). In the same period of time, 45.5% of the patients learnt to use the electronic voice aid, and only 16.1% learnt oesophageal speech. It took a whole year before all patient who eventually used oesophageal speech, had learned to handle it. Ambulant speech therapy was the predominant treatment leading to voice rehabilitation, followed by the support given by self-aid groups. A comparison of the various non-laryngeal speech patterns with regard to daily communication problems, and of the general satisfaction achieved with the type of non-laryngeal speech used, showed quantitative predominance of oesophageal speech as a positively rated method for voice restoration, even though a clear trend towards increased use of the voice prosthesis since its introduction is noticeable. PMID- 7986329 TI - [Laser surgical removal of salivary duct calculi]. PMID- 7986330 TI - [65th Annual Meeting of the German ENT Specialty, Head and Neck Surgery Society in Chemnitz 1994. Laryngology]. PMID- 7986331 TI - Autoreactive response in seronegative homosexual men at high risk for HIV infection. AB - Peripheral autoreactive T cell response was evaluated by limiting dilution analysis of autologous mixed lymphocyte reaction cultures in 15 subjects at high risk for HIV infection and in 20 normal individuals. The two groups did not show a quantitative difference of peripheral autoreactive T cells, but they showed different kinetics. While controls provided a straight line passing through the origin, the majority of high risk individuals showed a curve with a limited linear portion at high cell concentration, indicating that different mechanisms regulate the autoreactive response in the two groups studied. A follow-up study performed in three high risk and three normal individuals revealed a time dependent increase of peripheral autoreactive T cells only in high risk subjects. Such increase correlates with the decrease of CD4+ cell number and CD4+/CD8+ cell ratio. Furthermore, the proliferative response of the same three subjects to gp160 peptides suggests a specific cellular reactivity to HIV components. This work has potential importance in understanding some of the early events in HIV infection. PMID- 7986332 TI - Bovine x murine T-cell hybridomas specific for bovine herpesvirus 1 (BHV-1) glycoproteins. AB - Difficulties in the isolation and long-term maintenance of bovine herpesvirus-1 (BHV-1) specific T-cell clones have hindered the analysis of bovine cell-mediated immune response to this virus. In an effort to identify the T-cell epitopes of the virus, bovine murine T-cell hybridomas specific for BHV-1 were generated as an alternative to T-cell clones. Peripheral blood lymphocytes from a calf immunized with BHV-1 were restimulated in vitro with the virus to generate bulk T cell cultures. The antigen-specific T-cell-enriched bulk culture lymphocytes were fused with the T-cell receptor-deficient mutant of the murine thymoma cell line BW 5147. T-cell hybridomas were screened for their ability to produce interferon gamma in response to BHV-1 stimulation. Hybridomas with various specificities were obtained. One of them was specific for the BHV-1 glycoprotein gI, two were specific for gIV, while three other hybridomas were specific for gIII. One hybridoma responded to stimulation with BHV-1, but not to any of the glycoproteins gI, gIII, or gIV, suggesting that proteins other than these major glycoproteins may be involved in the bovine T-cell response to BHV-1. Of these hybridomas, one was MHC Class I restricted, while all the others were Class II restricted. PMID- 7986333 TI - Intact antiinfluenza virus immune response in targeted kappa-deficient mice. AB - Immunoglobulins are encoded by genes located in three different loci, the heavy chain (IgH), kappa light chain (Ig kappa), and lambda light chain (Ig lambda) loci. In mice, the kappa/lambda ratio of B cells is 95:5. In a previous study, we reported that kappa gene deletion causes the alternative usage of lambda 1 (93%) and lambda 2 (7%) light chains, and that the kappa anti-TNP repertoire is compensated for by the lambda repertoire even though the latter is clonally restricted in K-/- mice. To investigate the contribution of lambda antibodies to protection against virus, we compared K-/- mice with 129/Sv wild-type mice with respect to immune responses to influenza virus. PR8 virus immunized K-/- and 129/Sv mice showed no difference in the titer of anti-HA antibodies. Furthermore, the same immunized mice had sufficiently high neutralizing antibody titer to prevent infection when challenged with 7.5 x 10(4) TCID50 of PR8 virus. In addition, immunized K-/- mice were resistant to infection with 7.5 x 10(4) TCID50 and 7.5 x 10(5) TCID50 (10 and 100 LD50, respectively) of PR8 virus. Finally, K-/ mice are also capable of inducing cytotoxic T cells. These results suggest that the lambda repertoire can compensate for the kappa repertoire by generating a fully protective neutralizing antibody response. PMID- 7986334 TI - Immune response to secondary immunization with live or inactivated VZV vaccine in elderly adults. AB - Healthy varicella zoster virus (VZV) immune subjects > 55 years old, were immunized with 4,000 PFU of Oka strain VZV live vaccine or a similar amount of heat-inactivated vaccine. A subset of each group was also immunized with tetanus toxoid (TT) 3 months before receiving the VZV vaccine. The live and inactivated VZV vaccine groups had similar ages, sex distribution, and previous immunity to VZV. The live and inactivated VZV vaccines elicited similar increases in the frequency in blood of VZV-specific T cells, in vitro interferon-gamma production, and serum antibody levels both 3 and 12 months after immunization. Individuals with the highest responder cell frequency (RCF) at entry had the highest postimmunization RCF following either vaccine. There was no correlation at entry between the RCF to TT or RCF to VZV. There was a weak (P = 0.05) correlation in the incremental response to TT and VZV among individuals who responded to both vaccines. Entry variables that did not correlate with the response included percent of T cells or the CD45R0 (memory) T cell subset in blood, serum antibody levels, or amount of interferon-gamma production. The results indicate that the inactivated vaccine is safe for VZV-immune subjects and boosts their antibody and T-cell responses as effectively as the live vaccine for at least 1 year following immunization. PMID- 7986335 TI - CD3- and CD28-activating pathways in HCV infection. AB - We investigated the proliferative response and IL-2 receptor (IL-2R) expression in peripheral blood mononuclear cells (PBMC) activated with anti-CD3 mAb alone or in combination with anti-CD28 mAb in a group of hepatitis C virus (HCV)-infected patients with detectable viremia demonstrated by "nested" PCR. PBMC from HCV patients and controls showed similar proliferative responses either to anti-CD3 mAb, 64.1, and/or to anti-CD28 mAb, 9.3. No differences were found in anti-CD3 or anti-CD3 plus anti-CD28-induced proliferative responses between patients who demonstrated circulating PBMC bearing HCV-RNA when compared to those with negative HCV-RNA PBMC. Moreover, flow cytometry studies confirmed that anti-CD3 alone or in combination with anti-CD28 were able to induce a significant increase of IL-2R expression in patients or controls PBMC. Both groups showed similar basal CD28 expression. These results indicate that both CD3- and CD28-activating pathways are preserved in HCV-infected patients with chronic active liver disease. PMID- 7986337 TI - HIV-2-specific immune status of an HIV-2-exposed but uninfected cynomolgus monkey offspring. PMID- 7986336 TI - Immunogenicity study of a synthetic T-cell epitope of rubella virus capsid protein recognized by human T cells in different strains of mice. AB - The immunogenicity of a human immunodominant T-cell epitope C9 (residues 205-233) of rubella virus capsid protein was studied in three strains of mice using C9 lipopeptide. This peptide induced strong T-cell responses in all three strains of mice. The minimal T-cell epitope C9B (residues 205-216) recognized by human T cells with HLA-DR4 phenotype did not specifically stimulate proliferation of T cells from mice in vitro. T cells specific for C9 from immunized mice were shown to be CD4+, in agreement with results of similar studies in RV-seropositive humans. PMID- 7986338 TI - [Asthma by proxy (to latex of a condom). General review based on an observation]. AB - The AIDS progress in the world has led to a considerable increase in the request of medical gloves but also of condoms. At the same time latex hypersensitivity has a growing effect upon our allergology consultations; although the contact dermatitis and urticaria to condoms are frequent, asthma remains very rare. We report one case of condom nocturnal asthma in a patient also presenting a food allergy to sunflower with cross-reactivity to umbelliferae. The different steps of a latex allergy diagnosis are criticized, the populations at risk are mentioned. Nowadays, no standardized allergen exist, therefore we must put the stress on the prevention. Latex hypersensitivity raises an emergency public health issue. PMID- 7986339 TI - [The pork-cat syndrome: RAST inhibition test with Feld One]. AB - This work confirms that the common allergen in subjects who are doubly sensitized to cat and pork is quite different from that of subjects who are mono-sensitized to cat. The common protein is Albumin MW 67 Kda in the pork/cat syndrome, while the major allergen Feld One is characteristic in patients who are monosensitized to cat. PMID- 7986340 TI - [The pork-cat syndrome: effect of sensitivity to cats on that to pork meat. Based on an observation]. PMID- 7986342 TI - A simple activity assay for thrombin and hirudin. AB - Cloning of the thrombin cDNA has made it possible to study thrombin function by site-directed mutagenesis. Quantitative results from studies of thrombin mutants are often hindered by difficulties in assaying the enzyme activity. The high enzyme concentrations required for activity determination by standard methods limit their usefulness to thrombin mutants that cannot be readily produced in large quantities. We have developed a novel method using the synthetic substrate S-2238 and hirudin, a tight-binding inhibitor of thrombin, that allows for the active-site titration of thrombin at concentrations as low as 20 pM, with an error of < or = 5%. In addition, hirudin activity can be determined by this method to concentrations as low as 40 pM, with an error of < or = 5%. PMID- 7986341 TI - Potential beta PP-processing proteinase activities from Alzheimer's and control brain tissues. AB - Fluorogenic peptide substrates designed to encompass the reported alpha-secretory and amyloidogenic cleavage sites of the amyloid-beta precursor protein (beta PP) were used to analyze proteinase activities in brain extracts from control patients and those with Alzheimer's disease (AD). Activity against the secretory substrate at pH 7.5 in control and AD brains produced a major endopeptidase cleavage at the Lys687-Leu688 bond (beta PP770 numbering), consistent with the beta PP secretase cleavage. Activity in control brains against the amyloidogenic substrate at pH 7.5 produced one cleavage at the Ala673-Glu674 bond, two residues C-terminal to the amyloidogenic Met-Asp site. However, in three of four AD brains, the major cleavage was at the Asp-Ala bond, one residue from the amyloidogenic site. Both endopeptidase and carboxypeptidase activities in AD brains were lower than in control brains. Proteinase activities against the secretory substrate had a major optimum at pH 3.0-4.0 and another at pH 6.0-7.5. Proteinase activities against the amyloidogenic substrate had a major optimum at or below pH 3.0 and another at pH 6.0. Using both substrates, activities at low pH were higher in AD-brains than in controls, while at pH above 6.5, activities in control brains were higher than in AD. These results indicate that the levels of proteolytic enzymes in AD brains are altered relative to controls. PMID- 7986343 TI - Removal of the projection domain of microtubule-associated protein 2 alters its interaction with tubulin. AB - Microtubule-associated proteins (MAPs) can promote microtubule assembly in vitro. One of these MAPs (MAP2) consists of a short promoter domain which binds to the microtubule and promotes assembly and a long projection domain which projects out from the microtubule and may interact with other cytoskeletal elements. We have previously shown that MAP2 and another MAP, tau, differ in their interactions with tubulin in that tau, but not MAP2, promotes extensive aggregation of tubulin into spiral clusters in the presence of vinblastine and that microtuubles formed with MAP2 are more resistant than those formed with tau to the antimitotic drug maytansine [Luduena, R. F., et al. (1984), J. Biol. Chem. 259, 12890-12898; Fellous, A., et al. (1985), Cancer Res. 45, 5004-5010]. Here we have used chymotryptic digestion to remove the projection domain of MAP2 and examined the interaction of the digested MAP2 (ctMAP2) with tubulin in the presence of vinblastine and maytansine. We have found that ctMAP2 behaves very much like tau, but not like undigested MAP2, in the presence of vinblastine, in that ctMAP2 causes tubulin to polymerize into large clusters of spirals. In contrast, microtubule assembly in the presence of ctMAP2 is much more resistant to maytansine inhibition than is assembly in the presence of tau or undigested MAP2. Our results suggest that the projection domain of MAP2 may play a role in the interaction of tubulin with MAP2 during microtubule assembly. PMID- 7986345 TI - Conformational stability of alpha-lactalbumin missing a peptide bond between Asp66 and Pro67. AB - The peptide bond between Asp66-Pro67 of alpha-lactalbumin was cleaved with formic acid (cleaved alpha-lactalbumin). Secondary structural changes of the cleaved alpha-lactalbumin, in which the two separated polypeptides were joined by disulfide bridges, were examined in solutions of sodium dodecyl sulfate (SDS), urea, and guanidine hydrochloride. The structural changes of the cleaved alpha lactalbumin were compared with those of the intact protein. The relative proportions of secondary structures were determined by curve fitting of the circular dichroism. The cleaved alpha-lactalbumin contained 29% alpha-helical structure as against 34% for the intact protein. Some helices of the cleaved alpha-lactalbumin which had been disrupted by the cleavage appeared to be reformed upon the addition of SDS of very low concentration (0.5 mM). In the SDS solution, the helicities of both the intact and cleaved proteins increased, attaining 44% at 4 mM SDS. On the other hand, the helical structures of the cleaved alpha-lactalbumin began to be disrupted at low concentrations of guanidine hydrochloride and urea compared with that of the intact protein. However, no difference was observed in the thermal denaturations of the intact and cleaved proteins, except for the difference in the original helicities. The helicities of both proteins decreased with an increase of temperature up to 65 degrees C and recovered upon cooling. PMID- 7986344 TI - Folding pathway of guanidine-denatured disulfide-intact wild-type and mutant bovine pancreatic ribonuclease A. AB - The refolding kinetics of guanidine-denatured disulfide-intact bovine pancreatic ribonuclease A (RNase A) and its proline-42-to-alanine mutant (Pro42Ala) have been studied by monitoring tyrosine burial and 2'-cytidine monophosphate (2'CMP) inhibitor binding. The folding rate for wild-type RNase A is faster in the presence of the inhibitor 2'CMP than in its absence, indicating that the transition-state structure in the rate-determining step is stabilized by 2'CMP. The folding rate monitored by 2'CMP binding to the major slow-folding species of Pro42Ala RNase A is faster than the folding rate monitored by tyrosine burial; however, the folding rate monitored by inhibitor binding to the minor slow folding species is decreased significantly over the folding rate monitored by tyrosine burial, indicating that the major and minor slow-folding species of Pro42Ala fold to the native state with different transition-state conformations in the rate-determining step. PMID- 7986346 TI - Effect of extraction method on activities of polysaccharide-depolymerase enzymes in the microbial population from the solid phase in the rumen. AB - Samples of rumen digesta were collected from 2 cows fed with a 100:0 or 40:60 forage/concentrate diet 1 h before and 2 h after feeding. Enzymes from particle associated microorganisms were extracted by 5 different methods, including physical (freezing, grinding and sonication) or chemical and enzymatic (autolysis in a buffer, lysozyme and CCl4) treatments. Hydrolytic enzyme activities were measured on 3 polysaccharidic substrates: xylan, carboxymethylcellulose and Avicel cellulose. Contamination of enzyme preparations by feed proteins was evaluated. For the 3 substrates, the effect of feeding (sampling time and diet) on enzyme activities was independent of extraction method. Maximal activities were obtained with treatments including lysozyme and CCl4 or grinding in liquid nitrogen. Contamination of enzyme preparations by feed proteins was higher with chemical and enzymatic methods than with physical treatments. PMID- 7986347 TI - Effects of thymulin on in vitro incorporation of 3H-thymidine into gonocytes of newborn rat testes. AB - 3H-Thymidine incorporation into gonocytes was investigated by means of quantitative autoradiography in organ cultures of testes from newborn rats between day 0 (day of birth) and day 7, in the presence or absence of thymulin. The data indicated that thymulin had no effect on gonocyte incorporation on day 0 or on days 1 and 7; in contrast, thymulin had a strong effect on day 2. At day 2 the percentage of labeled gonocytes was 10-fold higher in experimental animals than in controls. Between days 2 and 6, thymulin had moderate activity. Thymulin thus appeared to have an age-dependent effect upon incorporation of 3H-thymidine into germ cells. On the other hand, in spite of a high incorporation rate of 3H thymidine into gonocytes after incubation with thymulin, the number of mitoses remained low, suggesting that thymulin may affect DNA duplication in gonocytes of newborn rat testes. PMID- 7986348 TI - [Effect of dietary fiber content reduction on digestive transit in the rabbit. Comparison and validation of models fitted to fecal marker excretion kinetics]. AB - The rate of passage (RP) in several digestive compartments was studied in 4 adult female rabbits cannulated at ileum, and receiving ad libitum 3 diets with decreasing fibre content (40, 30 and 22% NDF). The RP values in the whole digestive tract and between ileum and rectum were simultaneously measured by following the fecal kinetics of 2 markers (169Yb and 141Ce adsorbed on the NDF fraction of the diets) given as single doses. The mean retention time (MRT) in the whole tract provided by modelling methods (models: Grovum and Williams or Ellis) were similar to those obtained by reference method (numeric integration). MRT values in the caecum and the stomach were provided by models and were in good agreement with those deduced from reference measurements. Compared with the Ellis model, the Grovum and Williams model estimated more precisely the RP in tubular compartments (ie small intestine and distal colon); but the increasing part of the kinetics was better fitted using the Ellis model, particularly for low-fibre diets. The decrease in fibre intake (-50%) led to a 12 h increase (+72%) of the whole tract MRT, originating mainly from a 2-fold increase of ileo-rectal MRT. The MRT in the stomach decreased from 3 to 1 h, whereas the RP in the small intestine increased. Therefore, the oro-ileal MRT (mean 5 h) was not affected. A low dietary fibre induces a longer cecal MRT of large particles, without significant change for fine particles. PMID- 7986349 TI - Development of homologous radioimmunoassays for equine growth hormone and equine prolactin and their application to the detection of circulating levels of hormone in horse plasma. AB - Highly purified and well-characterised preparations of equine prolactin and growth hormone from equine pituitary glands were employed to set up highly sensitive and specific homologous radioimmunoassays (RIA) for the measurement of hormone in horse plasma. The limit of sensitivity of the GH RIA was 1.2 ng/ml with mean intra- and inter-assay coefficients of variation (CV) of 6.6 and 10%, respectively. The sensitivity of the equine prolactin (ePRL) RIA was 0.5 ng/ml with mean intra and inter-assay CV of 9.1 and 15.6%, respectively. Dose-response curves of a crude pituitary gland extract and plasma samples collected from a mare and foal were parallel to the standards and the PRL RIA was clinically validated by administration of thyrotropin-releasing hormone (TRH). Plasma samples taken at 15 min intervals over 24 h from lactating mares gave 24 h mean GH values in the range 5.5 to 7.95 ng/ml. Large intermittent elevations of GH activity were detected. The mean 24 h PRL concentrations were between 3.2-10.4 ng/ml in the lactating animals, with higher concentrations earlier in lactation. Long episodic bursts of PRL were detected. PMID- 7986351 TI - Effect of undernutrition on the ability of the sheep rumen to absorb volatile fatty acids. AB - The ability of the rumen to absorb the same quantity of VFA with 4 animals previously fed with 2 levels of intake was tested. Animals received maintenance (P1) and half maintenance (P2) energy and nitrogen requirements successively. Absorption was measured with the empty washed rumen technique. Three litres of a solution buffered at pH 6.30 containing VFA (C2:57.1, C3:49.2 and C4:7.4 mM or C2:79.8, C3:23.5 and C4:11.5 mM) and CoEDTA (7.1 mg Co/l) were introduced in the rumen and regularly sampled for 3 h. VFA absorption was linear during the trials. Rates of absorption were expressed as mmol/h or percentage of initial quantity/h for the comparison between VFA. The order of absorption rate (%/h) was C4 > C3 > C2. Water absorption was not significantly different between the periods whereas VFA absorption rates (mmol/h) were significantly reduced after undernutrition. Composition of the solution had no significant effect on VFA absorption rate (%/h). PMID- 7986350 TI - Development of bovine embryos in vitro following oocyte maturation under defined conditions. AB - A total of 4,615 immature bovine oocytes were used in a series of experiments aimed at the systematic evaluation of the role of the different components of our in vitro maturation (IVM) medium in imparting developmental competence to the oocytes. The results clearly demonstrate that both tissue culture medium 199 (M199) and synthetic oviduct fluid (SOF) are capable of supporting the IVM of bovine oocytes at high rates in the absence of macromolecular supplements, as evidenced by subsequent development to the blastocyst stage (20 and 25%, respectively). However, both were significantly lower than the control (containing 10% fetal calf serum, 5 micrograms/ml pLH (porcine luteinizing hormone), 1 microgram/ml pFSH (porcine follicle-stimulating hormone), and 1 microgram/ml-17 beta-estradiol, E2) in terms of blastocyst yield. Inclusion of bovine serum albumin (3 mg/ml) was not beneficial and in fact significantly depressed development when added to SOF. It was shown that the advantage of the control conditions over unsupplemented M199 and SOF was entirely attributable to the presence of serum and that in the absence of serum the inclusion of the above hormone cocktail significantly depressed postcleavage development. When used individually, neither LH (50, 500, 5,000 ng/ml) nor FSH (10, 100, 1,000 ng/ml) improved development over M199 alone. In conclusion, we now have a simple maturation system, using a fully defined medium (M199) in which the search for factors improving the cytoplasmic competence acquisition of maturing cattle oocytes will be possible. PMID- 7986352 TI - Rate of [15N]leucine incorporation and determination of nitrogenous fractions from gastro-jejunal secretion in fasting humans. AB - The aim of this study was to quantify the nitrogen fraction flow rates in gastro jejunal secretions in fasting humans and to determine the [15N]leucine incorporation into the secreted proteins. A double lumen intestinal perfusion method was used in 5 healthy volunteers. Plasma and gastro-jejunal juices were collected during a 15-h intravenous [15N]leucine infusion. Total, soluble and insoluble nitrogen, amino acids and [15N]leucine enrichment were measured. The total nitrogen flow rate was 7.2 +/- 1.9 mmol.h-1 and 58% was ethanol soluble. The amino-acid composition remained constant and glycine was the most abundant. The plasma [15N]leucine enrichment at the isotopic plateau was 4.8 +/- 0.9 mol% excess. The [15N]leucine enrichment in the intestinal chyme increased asymptotically to reach a plateau after 5 h. The [15N]leucine enrichment at the plateau and the fractional synthesis rate of secreted proteins were 1.6 +/- 0.5 mol% excess and 21.5 +/- 3.3%.h-1, respectively. These results show that the composition of the basal gastro-jejunal secretion is very stable. A part of this secretion is composed of proteins with rapid synthesis rates. PMID- 7986353 TI - Plasma apolipoprotein VLDL-II and egg production in laying hens: establishment of an ELISA method. AB - The developmental pattern of apolipoprotein VLDL-II (apo-II) in the plasma with regard to lipid concentration was characterized during the transition of pullet females to the laying phase in commercial laying hens (Gallus domesticus). Apo-II was isolated from the plasma of estrogen-administered roosters, and a rapid ELISA was developed for its quantification in chickens. The sensitivity of the assay was 5 ng/ml, and the inter- and intra-assay coefficients of variation were 4 and 8%, respectively. Whereas no detectable levels of apo-II could be monitored in the blood plasma of immature chickens, the level increased slightly to 23 weeks of age and sharply at the onset of lay. This profile reflects the dramatic changes in lipid metabolism at the onset of lay, and concurs with the concentration of total lipids in the plasma and with egg production rate. Plasma apo-II of 2 laying strains differing in body weights but compared at approximately similar egg production rates, tended to be slightly higher in heavy vs light-weight type hens. Oogenesis was speculated to be the main factor affecting both apo-II and total lipid profiles in chicken plasma, enabling efficient delivery of VLDL to the egg. PMID- 7986354 TI - Relationships between broodiness expression laying persistency and concentrations of hormones during the first productive period in turkey hens (Meleagris gallopavo). AB - The changes in egg production, in broodiness index and in plasma concentrations of LH, prolactin, oestradiol and progesterone were monitored throughout the first period of laying in turkey hens. The hens were subsequently classified according to their ability to express broodiness (33%) and their laying persistency; 25% were out-of-lay by the end of the experiment. A high percentage (67%) of the hens that went out-of-lay had previously been identified as broody. Altogether, a significant (p < 0.05) physiological stage effect was found when comparing prolactin, oestradiol and progesterone data obtained from short and long laying persistency hens and this stage effect was also significant for oestradiol and progesterone data obtained from broody and non-broody hens. Otherwise, plasma LH concentrations decreased slightly but significantly throughout the laying year in all hens but no significant differences between physiological states were observed, although the decrease was more pronounced in the hens that went out-of lay. Plasma progesterone concentrations remained stable throughout in laying hens but decreased significantly in broody and/or out-of-lay hens. Plasma prolactin concentrations were maximal between the 5th and 12th week of egg production and the levels observed in laying hens that did not become broody or had a long laying persistency were twice those measured in broody and/or out-of-lay hens. In the meantime, plasma oestradiol concentrations were lower and stable in laying hens, whereas they were higher during the first half of the productive period in broody and short laying persistency hens. These results suggest that, under our experimental conditions, the hormonal profiles of prolactin and oestradiol for a given hen during the first 10 weeks of the laying cycle may provide predictive information for future changes in its physiological status. The inverse relationship that was observed here between high early plasma concentrations of oestradiol and laying persistency is original. In addition, the relationship between the ability to express broodiness and high and low early plasma concentrations of oestradiol and prolactin, respectively, in hens submitted to preventive broody treatment has not been reported previously. Furthermore, it seems clear that high initial concentrations in prolactin, far from exerting any deleterious effects on egg production are closely associated with a longer persistency of egg laying. PMID- 7986355 TI - [Education of Mexican health personnel on AIDS]. AB - We describe the epidemiology of AIDS as it pertains to health workers in Mexico. Of the 12,151 cases notified in adults up until 1993, 2.9% occurred among such workers. Two cases of occupational transmission have been documented. Seroprevalence surveys have shown an infection rate of less than 0.1%. Nonetheless, the frequency with which hepatitis B viral markers are present (11.8% of anti-HBs antibody carriers and 2% of anti-HBsAg antibody carriers) points to the fact that mechanisms for the transmission of both types of viruses are at work. Surveys conducted among health workers to explore their knowledge and attitudes on the subject of AIDS indicate that they share many false notions about the disease and that they stigmatize its victims. Educational campaigns have improved knowledge about the illness but have not modified people's attitudes significantly. Holding workshops has proved to be the most useful strategy for attitude modification. We describe a few strategies that may be useful for changing negative attitudes among health personnel. When calculating the frequency with which biosafety measures are implemented, it has been noted that their application is erratic. Epidemiologic studies have confirmed the existence of an association between the time of occupational exposure and the presence of hepatitis B viral markers. Many people reject adopting certain measures, such as anti-hepatitis vaccination. Finally, we analyze the need for continuous training and supplies if increased biosafety measures are to be adopted. PMID- 7986356 TI - [GLOEPI. English-Spanish glossary of epidemiology and health statistics terms]. PMID- 7986357 TI - [Tuberculosis and AIDS in Venezuela]. PMID- 7986358 TI - Primitive neuroectodermal tumors of the central nervous system in childhood: tumor biological aspects. PMID- 7986359 TI - Antigen presentation, aberrant glycosylation and tumor progression. PMID- 7986360 TI - Pathogenesis of autoimmune hemolytic anemia in New Zealand black mice. PMID- 7986361 TI - Young children's performance on a task sensitive to the memory functions of the medial temporal lobe in adults--the delayed nonmatching-to-sample task--reveals problems that are due to non-memory-related task demands. AB - Delayed nonmatching-to-sample performance was examined in children and found to be poor from 12 months until almost 2 years even at 5-s delay, although 5 s is well within such children's memory capacity. After 12 months of age, performance did not differ by delay (5 or 30 s). Because children's problems seemed largely unrelated to the task's memory demands, the 2 final studies explored the role of other cognitive abilities (deduction of an abstract rule, speed of processing, and resistance to interference or distraction). Telling children the rule or quadrupling sample presentation time had little effect. Because a salient stimulus (the reward) might interfere with keeping one's attention on the sample, the reward was omitted during initial sample presentation. This helped; at the 5 s delay, 15-month-olds performed at least as well as 21-month-olds in the basic condition, and 12-month-olds performed almost as well. Implications for the cognitive abilities improving during the 2nd year and for the functions of the medial temporal lobe are discussed. PMID- 7986362 TI - Relation of spatial learning of rats in the Morris water maze task to the number of viable CA1 neurons following four-vessel occlusion. AB - Male Wistar rats were tested in the Morris water maze task 1 week after 6, 9, or 12 min of transient global ischemia. The 9-min and 12-min ischemia groups were significantly impaired in the acquisition and the reversal experiment. A systematic counting of CA1 neurons in the whole hippocampal formation revealed a unilateral number of CA1 neurons of 286,000 in the sham group, of which 2/3 were located in the dorsal hippocampus. The ischemia groups showed a significant decline in the number of dorsal CA1 neurons, whereas only the 12-min ischemia group showed a significant but minor decline (10%-15%) in the number of ventral CA1 neurons. A correlation analysis showed that the escape distance declined with increasing number of viable CA1 neurons, but poor correlation coefficients were obtained. Thus, some of the ischemic rats with even very few viable CA1 neurons in the dorsal hippocampus were capable of performing this spatial learning task at sham-group level. PMID- 7986363 TI - Forgetting in rats following medial septum or mammillary body damage. AB - This study examined the effects of medial septal (MS) and mammillary body (MB) radio-frequency lesions in an automated delayed-matching-to-sample (DMTS) procedure using lever-position stimuli and rats. Memory performance pre- and postsurgery was assessed with a negative exponential decay function fitted to bias-free measures of recognition. Part 1 showed that MS, but not MB or sham control surgery, impaired DMTS performance. This impairment in the MS group was best characterized as an increase in the rate of forgetting. Part 2 examined the interaction between MS and MB lesion effects and proactive interference arising from responses made on the previous DMTS trial. The results indicated that proactive interference effects were similar for all groups. These results provide further support for the critical role of the MS region in memory function but indicate that damage to this brain region does not disrupt memory function through a heightened sensitivity to proactive interference. PMID- 7986364 TI - Prepulse inhibition of the startle response in mice: relationship to hearing loss and auditory system plasticity. AB - Prepulse inhibition was used with C57BL/6J (C57) mice to assess behavioral perceptual correlates of previously demonstrated physiological changes in the central auditory system associated with age-related hearing loss. Normal-hearing CBA/CaJ (CBA) mice and DBA/2J (DBA) mice, which exhibit extremely rapid hearing loss, were also tested. Tone prepulse stimuli (S1s) were presented 100 ms prior to a startle-evoking noise stimulus (S2), and a decrease in startle amplitude served as the measure of startle modification. As high-frequency hearing declined in C57 mice between 1 and 12 months of age, the efficacy of lower-frequency S1s was significantly enhanced. CBA mice exhibited no age-related changes in startle modification. DBA mice exhibited changes similar to those observed in C57s but at an accelerated rate. The enhanced behavioral saliency of low and middle frequencies in C57 and DBA mice appears to be a consequence of neural plasticity in the central auditory system. PMID- 7986365 TI - Lesions of the pontine parabrachial nuclei eliminate successive negative contrast effects in rats. AB - Rats shifted from a high to a low concentration of sucrose make fewer licks for the low concentration than rats that experience only the low concentration of sucrose. This phenomenon, referred to as successive negative contrast, is eliminated after bilateral electrolytic lesions of the amygdala. Because the amygdala receives direct projections from the gustatory zone of the parabrachial nuclei of the pons (PBN), this experiment was designed to examine this phenomenon in rats with electrophysiologically guided bilateral electrolytic lesions of the PBN. The results of this experiment showed that lesions of the PBN fully prevent contrast in rats shifted from the high to the low concentration of sucrose. Thus, an intact PBN is essential for the occurrence of successive negative contrast effects in rats. PMID- 7986366 TI - Activation of Fos-like immunoreactivity in the medial preoptic area and limbic structures by maternal and social interactions in rats. AB - The researchers examined the number of cells showing Fos-like immunoreactivity (Fos-lir) in the brains of hormonally primed parturient rat dams immediately following their first behavioral interactions with pups. Groups were exposed to newborn pups (pup), adult conspecifics (social), or a new food (food), or they were left alone in cages (control/isolate) for a 1-hr period. Rats were then killed, and their brains were prepared for immunohistochemical detection of Fos lir. Rats in the pup group had higher numbers of cells showing. Fos-lir within the medial preoptic area (MPOA) nuclei than did the social, control/isolate, and, marginally, food groups and higher levels of Fos-lir in a number of amygdaloid nuclei (medial and cortical) and in cingulate and somatosensory cortices than did control/isolate or food groups. Fos-lir in amygdala did not differ between pup and social groups. There were also group differences in Fos-labeling in the olfactory bulbs, with the pup group showing the highest densities. These results show elevated expression of Fos-lir in brain structures that were activated during the expression of maternal behavior, including the olfactory structures, amygdala, and MPOA. PMID- 7986367 TI - Hypothalamic knife cuts that disrupt mating in male gerbils sever efferents and forebrain afferents of the sexually dimorphic area. AB - The sexually dimorphic area (SDA) of the gerbil hypothalamus is essential for male sexual behavior. To determine (a) if the SDA can affect mating via laterally projecting axons and (b) which SDA afferents might affect mating, male gerbils were given bilateral, parasagittal knife cuts lateral to the medial or lateral SDA. Others were given cuts with a knife coated with horseradish peroxidase to label cells of which axons were cut. Medial cuts eliminated mating and consistently labeled cells in the medial SDA. Lateral cuts did neither. Medial cuts also labeled more cells in the ventral part of the lateral septal nucleus, the encapsulated part of the bed nucleus of the stria terminalis, the medial nucleus of the amygdala, the amygdalohippocampal area, and the ventral premammillary nucleus than lateral cuts did. Thus, medial cuts may disrupt mating by severing SDA efferents or by severing SDA afferents from 1 or more of these 5 sites. PMID- 7986368 TI - Telencephalic connections of the sexually dimorphic area of the gerbil hypothalamus that influence male sexual behavior. AB - The sexually dimorphic area (SDA) of the gerbil hypothalamus is essential for mating in male gerbils. To determine if it affects mating through its connections with the ventral part of the lateral septal nucleus (LSv), the caudal part of the medial bed nucleus of the stria terminalis (caudal BSTm), or the medial amygdala amygdalohippocampal area (MA-AHi), these connections were severed. Unilateral cell-body lesions were made in the SDA and in the contralateral LSv, caudal BSTm, or MA-AHi. Controls received the same lesions ipsilaterally. Other gerbils received lesions in the caudal BSTm and contra- or ipsilateral MA-AHi. Only contralateral lesions of the SDA and caudal BSTm severely impaired mating. Because contralateral lesions of the SDA and MA-AHi, or BSTm and MA-AHi, did not mimic this effect, the BSTm neurons that are needed for male sexual behavior through their connections with the SDA do not simply relay information to or from the MA-AHi. PMID- 7986369 TI - Preoptic and subthalamic connections with the caudal brainstem are important for copulation in the male rat. AB - Bilateral lesions of either the medial preoptic area/anterior hypothalamus (MPAH) or a subthalamic region that includes the caudal zona incerta eliminate copulation in male rats. Pathways connecting the MPAH and subthalamus with the caudal brainstem may help regulate sexual behavior. Experiment 1 showed that bilateral coronal transections of the pontine tegmentum reduce mating and that the combination of a unilateral tegmental cut with a contralateral excitotoxin lesion of either the MPAH (Experiment 2) or subthalamus (Experiment 3) virtually eliminates copulation. Asymmetric bilateral damage appears to eliminate mating through a bilateral effect common to the transection and the lesion--the destruction of connections linking the MPAH and subthalamus with the caudal brainstem. These results indicate that preoptic and subthalamic connections with the caudal brainstem are important for copulation in the male rat. PMID- 7986370 TI - Abdominal vagotomy alters the structure of the ingestive behavior of rats ingesting liquid diets. AB - A microstructural analysis of the licking behavior of the rat was used to investigate the effects of total abdominal vagotomy on ingestive behavior. Vagotomy decreased the meal size of milk and 3 concentrations of sucrose. The decrease was due to an increase in the decline in the rate of licking during the meal, suggesting that negative feedback from the gastrointestinal tract was enhanced by vagotomy, perhaps because of accelerated clearance of fluid from the stomach to the intestine. No evidence was found for motor dysfunction of licking or alterations in gustatory sensitivity to the test solution. The results suggest that vagotomy enhanced the strength of an extravagally mediated negative feedback signal from the intestine and that the vagus nerve normally prevents this from occurring by regulating gastric clearance. PMID- 7986371 TI - Bombesin suppresses need-free and need-induced salt intake in rats. AB - The researchers performed experiments to evaluate whether the effects of bombesin are selective for the satiation of ingestive behaviors related to energy balance or if ingestive behaviors associated with sodium balance are also suppressed by bombesin. Injections of 4 and 8 micrograms/kg bombesin reliably reduced need-free and sodium deficiency-induced NaCl intake in male rats. The effects of bombesin on the sodium-deficiency-induced change in taste reactivity was assessed. Injections of 4 micrograms/kg and 8 micrograms/kg bombesin had no effect on the sodium deficiency-induced shift in taste reactivity. These data indicate that bombesin suppresses NaCl intake and that bombesin does not appear to interact with gustatory sensibility in exerting its behavior-controlling action. PMID- 7986372 TI - Behavioral sensitization to drug stimulant effects in C57BL/6J and DBA/2J inbred mice. AB - Common features shared by addictive drugs have been difficult to identify. One ubiquitous effect of these drugs is psychomotor stimulation. Further, repeated exposure commonly results in sensitization to drug stimulant effects. This study evaluates sensitization to drugs from several drug classes in C57BL/6J and DBA/2J inbred strain mice. DBA/2J mice showed sensitized responses to ethanol and methamphetamine, whereas C57BL/6J mice developed sensitization to morphine and methamphetamine. Strain susceptibilities to ethanol- and morphine-induced sensitization closely paralleled their sensitivities to the acute stimulant effects of these drugs; this was not the case for methamphetamine. The relative sensitivities of DBA/2J and C57BL/6J mice were not consistent across drugs, suggesting that the stimulant and sensitized responses to these drugs may be mediated by at least partially divergent neural mechanisms. PMID- 7986373 TI - Interocular transfer in the split-brain rat. AB - After the 1991 development of a method to transect the optic chiasm in the rat, the authors investigated interocular transfer in split-chiasm rats with corpus callosum section and callosum intact. Rats were monocularly trained on an orientation discrimination, reversed with the other eye, and retrained with the 1st eye on the 2nd-eye problem or reversal. In split-chiasm rats, the 2nd-eye S+ (correct stimulus) showed strong transfer (55% savings) to the 1st eye. S- (incorrect stimulus) did not; reversal and transfer groups differed significantly. Split-brain rats retrained with the 1st eye on the 2nd eye S+ required no more trials than original learning, as if they had not experienced this problem. Split-brain rats retested with the original S+ showed modest (19%) savings. The findings establish interhemispheric communication via the callosum and suggest, as in findings of cat and monkey studies, the disruption of transfer by callosal section. PMID- 7986374 TI - DBA/2 and C57BL/6 mice differ in contextual fear but not auditory fear conditioning. AB - It has been proposed that DBA/2 and C57BL/6 mice perform differently on some learning and memory tasks because of functional differences in the hippocampal formation. To evaluate this hypothesis, DBA/2 and C57BL/6 mice were tested on 2 forms of conditioned fear: contextual fear conditioning, which depends on the integrity of the hippocampal formation, and auditory cue conditioning, which does not. Both mouse strains displayed equivalent conditioning when the auditory cue was paired with shock, but DBA/2 mice showed significantly less conditioning to the context in which shock was experienced. These results are consistent with the hypothesis that the pattern of spared and impaired performance, which DBA/2 mice display on a variety of learning and memory tasks, is related to impaired hippocampal formation function. PMID- 7986375 TI - Tactile extinction following unilateral lesions in the rat anteromedial cortex: effects of a contralateral cue. AB - Following unilateral lesions of the anteromedial cortex (AMC) or the caudal forelimb representation (CFL), rats prefer to remove an adhesive patch placed on the forelimb ipsilateral to the lesion before removing a simultaneously applied contralateral patch (i.e., ipsilateral asymmetry). The present experiment was designed to investigate the possibility that attention has some role in these asymmetries. Specifically, the researchers investigated whether a contralateral tactile cue presented before the simultaneous presentation of bilateral tactile stimuli would neutralize the ipsilateral asymmetry. In rats with AMC lesions, the contralateral cue neutralized the ipsilateral bias, whereas the cue had no effect on rats with CFL lesions. These data suggest that the ipsilateral bias observed in AMC-damaged rats may reflect an impairment in attention. PMID- 7986376 TI - An in vitro amplification approach for the expression of recombinant proteins in mammalian cells. AB - A method for the expression of recombinant DNA products in mammalian cells based on in vitro amplification of gene units is described. Gene cassettes containing either a selectable marker or the gene of interest are mixed at different molar ratios, and linear polymers are formed using forced head-to-tail ligation. After introduction of the polymers into mammalian cells, transformants with various amounts of the amplified gene unit are obtained. For a first characterization of the system, the gene coding for chloramphenicol acetyltransferase (CAT) has been used to produce polymers containing a single neomycin-resistance gene ligated to different numbers of CAT gene units and used for transfection into HeLa cells. All isolated G418 (gentamycin)-resistant cell transformants which received in vitro amplified DNA were found to express high levels of CAT activity in a stable manner. Southern-blot analysis of individual clones revealed multiple copies of the gene integrated head-to-tail in the genome. This system allowed us to express the gene coding for human prepro-endothelin-1 in A617 human vascular-smooth muscle cells. The recombinant protein was shown to be correctly processed and biologically active endothelin-1. PMID- 7986377 TI - Ethanol adaptation mechanisms in Saccharomyces cerevisiae. AB - Determination of the membrane lipid composition of Saccharomyces cerevisiae revealed an increase in the unsaturation index, qualitative and quantitative changes in sterol content and an alteration of the activity of the plasma membrane ATPase when cells were pre-adapted to ethanol. All these changes may constitute different adaptation mechanisms which allow the cell to cope with ethanol stress. The importance of the lipid environment on the plasma membrane ATPase activity is also discussed. PMID- 7986378 TI - Purification and characterization of the endocellular beta-glucosidase of a new strain of Candida entomophila isolated from fermenting agave (Agave sp.) juice. AB - A yeast strain isolated in the laboratory from fermenting agave (Agave sp.) juice was studied and classified as Candida entomophila. The beta-glucosidase of this yeast was purified by ion-exchange chromatography and gel filtration. Its molecular mass estimated by gel filtration was 400 kDa. The oligomeric structure was determined following treatment of the purified enzyme with SDS. Its optimum pH was between 5 and 6, and its optimum temperature was 60 degrees C. The enzyme was active against soluble glucosides with (1-->3)-beta, (1-->4)-beta and (1-->4) alpha linkage configuration, and it possesses (1-->6)-alpha-arabinofuranosidase activity. It is competitively inhibited by glucose and by D-gluconic acid lactone. The enzyme was constitutive and a glucosyltransferase activity is observed in the presence of ethanol. Since the glycosides present in wines and fruit juices represent a potential source of aromatic flavour, the possible use of the yeast glucosidase for the liberation of the bound aroma is discussed. PMID- 7986379 TI - Effect of environment on insulin-like growth factor I refolding selectivity. AB - Recombinant human insulin-like growth factor I (IGF-I), a 70-amino-acid peptide containing three disulphide bonds, produces two monomeric and several multimeric species during refolding. To optimize production of correctly folded IGF-I, conditions which influence protein refolding, stability and solubility were systematically examined. Combinations of solution components and conditions were analysed to identify synergistic interactions which enhance or reduce refolding efficiency. IGF-I concentration had the largest effect on formation of correctly folded peptide, due to competing association reactions. Solution polarity had the next largest individual effect, both on the level of multimeric peptide and on the relative proportion of correctly folded to misfolded monomeric peptide. Salt type and concentration and chaotrope type and concentration also had large individual effects on the distribution of IGF-I forms produced. Solution polarity modulated the effects of many other conditions including chaotrope concentration, salt type and concentration, and osmolyte concentration. Simultaneously decreasing the solution polarity and increasing the salt concentration improved the yield of correctly folded IGF-I relative to either individual change. Optimum solution conditions for refolding were 2M urea, 1M NaCl and 20% (v/v) ethanol. A possible mechanism for the importance of solution polarity on IGF-I refolding is discussed. PMID- 7986381 TI - Photolinker-polymer-mediated immobilization of monoclonal antibodies, F(ab')2 and F(ab') fragments. AB - Photolinker-polymer-mediated covalent immobilization of antibodies, F(ab') and F(ab')2 fragments has been achieved by light-dependent coupling procedures. Anti alpha-foetoprotein (anti-AFP) monoclonal antibodies were covalently linked to microplates by layer-coating procedures, which entail antibody photoimmobilization to a photolinker-polymer-precoated surface. In this and the co-coating procedure described, diazirine-functionalized BSA (T-BSA) served as the multifunctional light-activatable linking agent (photolinker polymer). Prior to photo-activation, F(ab')2 or F(ab') fragments derived from anti-(prostate specific antigen) monoclonal antibodies were mixed and co-coated with the photolinker polymer on to polystyrene microplates. The immunoreagents remained immunologically active after 350 nm irradiation (irradiance 0.7 mW.cm-2 for 20 min). Immuno-responses of photoimmobilized monoclonal anti-AFP antibodies were equivalent to signal intensities obtained with physically adsorbed antibodies. Photoimmobilization of anti-PSA F(ab') fragments in the presence of T-BSA revealed exponential binding characteristics indicating stabilizing molecular co operativity of the BSA constituent. Co-coating procedures yielded 62 and 65% binding of applied 14C-labelled F(ab')2 and F(ab') fragments respectively. Covalency of antibody binding was inferred from: (i) the strict dependence of photoreagent availability; (ii) the light-dependence of the immobilization process; and (iii) the reversibility of immunocomplexation after acid treatment. PMID- 7986380 TI - Antisense peptides to the 43-57 region of acylphosphatase and to the 46-60 region of two isoenzymes of a low-M(r) phosphotyrosine protein phosphatase do not interact with the corresponding proteins. AB - Three peptides complementary to exposed regions of two low-M(r) phosphotyrosine protein phosphatase isoenzymes and of the acylphosphatase muscle isoenzyme have been synthesized. Each peptide was synthesized on two different types of resins; the peptides were anchored to the resins by amide linkages. The peptide resins were checked by amino acid analysis and Edman degradation and directly used for enzyme purification. Despite our attempts, none of the resins was able to bind significant amounts of the corresponding protein, indicating the lack of interaction between the three proteins and the corresponding complementary peptides. This result agrees with many other reports, confirming that the molecular-recognition theory has no general validity. PMID- 7986382 TI - Purification and characterization of an extracellular adenosine deaminase from Nocardioides sp. J-326TK. AB - An extracellular adenosine deaminase was isolated from the culture supernatant of Nocardioides sp. J-326TK and purified 193-fold to homogeneity. It had a specific activity of 4677 units/mg at 37 degrees C, was a monomeric protein as judged by SDS/PAGE, and was characterized with respect to M(r) (80,000 and 72,000 by gel filtration on Sephadex G-200 and SDS/PAGE respectively), pH optimum (6.0), temperature optimum (50 degrees C) and pI (7.6). The adsorption spectrum of the enzyme had a maximum at 280 nm and a minimum at 250 nm. The enzyme was stable at pH 6.5-7.5 and at temperatures below 30 degrees C. Adenosine and 2' deoxyadenosine were deaminated and the respective Km values were 0.22 and 0.20 mM, but the enzyme was not active on adenine and 6-(gamma gamma' dimethylallylamino)purine riboside. The enzyme reaction was promoted by Fe3+ and Sn2+, but potently inhibited by Hg2+, Ag2+, o-phenanthroline and pentachlorophenol, and noticeably inhibited by 8-bromoadenosine, theobromine and theophylline. PMID- 7986383 TI - Multichannel flow-injection-analysis biosensor system for on-line monitoring of glucose, lactate, glutamine, glutamate and ammonia in animal cell culture. AB - The application of a chemiluminometric method for the on-line monitoring of a hybridoma cell culture is described. Enzyme sensors for glucose, lactate, glutamine, glutamate and ammonia, based on oxidase-catalysed reactions, were developed and connected to a flow-injection-analysis (f.i.a.) biosensor. H2O2 produced by the oxidase-catalysed enzyme reaction was detected by luminol chemiluminescence with a fibre-optic H2O2 biosensor. The system has been used to monitor animal cell cultures. A continuous hybridoma cell cultivation for the production of monoclonal antibodies is presented as an example. It was possible to monitor the bioprocess over a period of 15 days. A complete analysis of all five components could be performed within 42 min. The enzyme sensors were stable during the whole cultivation time without significant loss of activity. The computer-controlled biosensor f.i.a. works with good reliability. The precision for all five components ranged between 2.2 and 4.5%. It was possible to determine glutamine in one step using an anti-interference enzyme reactor. Endogenous glutamate was completely removed up to a level of 0.5 mM. PMID- 7986384 TI - Attenuated release of atrial natriuretic peptide and vasorelaxation in streptozotocin-induced diabetic rats. AB - The present study was aimed at investigating the atrial natriuretic peptide (ANP) and urinary responses to acute perturbations in fluid balance and the vascular function in diabetes mellitus (DM). DM was induced in rats by treatment with streptozotocin (50 mg/kg, i.p.). Ten weeks later, the plasma ANP concentration measured in the conscious state was significantly higher in DM group (27.5 +/- 3.9 pg/mL) than in the control (15.4 +/- 2.6 pg/mL), while the atrial tissue contents of ANP were lower. In response to acute extracellular volume expansion (VE), amounting up to 5% of body weight over 45 min, under thiopental anesthesia (50 mg/kg, i.p.), the magnitude of increase in plasma ANP was lower in the DM group than in the control (56.8 +/- 25.2 vs. 189.1 +/- 53.6% increases over the basal). Urinary sodium excretion during VE was also lower in the DM group. Acetylcholine-induced relaxation of the isolated aortic rings was attenuated in the DM group, which was partially restored by L-arginine-supplementation (2 g/L in drinking water). These results suggest that body fluid homeostasis and vascular functions are unfavorably altered in DM. PMID- 7986385 TI - Mechanisms of hyperkalemia associated with hyporeninemic hypoaldosteronism in streptozotocin-induced diabetic rats. AB - This study was aimed at investigating the mechanisms of clinically important overt hyperkalemia in diabetes mellitus with underlying hyporeninemic hypoaldosteronism known as a classic model of the syndrome of hyporeninemic hypoaldosteronism (SHH). Rats (Sprague-Dawley, male) were streptozotocin-treated (60 mg/kg, ip) and used after 60 days. Rats with plasma glucose levels higher than 300 mg/dL (mean +/- SEM, 423 +/- 20 mg/dL, n = 8) were selected as the diabetic group. Age-matched normal rats served as control (mean plasma glucose, 88 +/- 2, mg/dL, n = 8). Serum potassium concentrations and osmolalities as well as serum creatinine levels were significantly higher in the diabetic than in the control group (5.07 +/- 0.09 vs. 4.68 +/- 0.11 mEq/L; 330 +/- 14 vs 290 +/- 3 mOsm/L; 0.40 +/- 0.03 vs 0.31 +/- 0.02 mg/dL, p < 0.05). Plasma renin activity (PRA) in the diabetic group was significantly lower than that in the control group (6.0 +/- 1.0 vs 12.1 +/- 1.1 ng Al/ml/h, p < 0.001). Plasma aldosterone concentration (PAC) was also significantly lower in the former than in the latter (368 +/- 30 vs 761 +/- 57 pg/ml, p < 0.001). Renomegaly, abnormal distal tubular cells with few organelles, and increased lipid droplets with pyknotic nucleus in zona glomerulosa of the adrenal glands were noted in the diabetic group. In conclusion, multifactorial causes including insulinopenia, hyperosmolality, elevated serum creatinine level and hypoaldosteronism with possible contribution of altered distal tubular response to aldosterone may have interacted to develop hyperkalemia in these diabetic rats. PMID- 7986386 TI - Morphological study of surgically induced open neural tube defects in chick embryos--postoperative 24 hours. AB - For the experimental study of neural tube defect (NTD), a surgical model has advantages over other models in a few aspects. It causes less functional derangement of cells and the NTDs can be made selectively by surgery. The authors planned to use the surgical model for the experimental study of NTD. As the first step for the studies, the chronological changes of morphology during the early postoperative period were investigated using postincubation 3-day chick embryos. The objectives of this study are (1) the morphological evaluation of the surgical model as a method for studies of open NTD, and (2) the observation of morphological changes for the first 24 hours after surgery which include 'overgrowth' appearance and the continuity between the surface ectoderm and the neuroectoderm. The morphological changes were observed by light microscope and scanning electron microscope. Immediately after surgery, typical open NTDs were observed. Morphologically they were very similar to the appearance of spontaneous (non-surgical) open NTDs. The opened neural tubes were everted progressively and they looked rather flat at 24 hours after surgery. Cellular hyperplasia ('overgrowth' appearance) was noted within 24 hours after surgery and became more prominent during the 24 hours. There was increasing continuity between the surface ectoderm and the neural tissue until 24 hours after surgery when the continuity looked almost complete. In conclusion, surgically induced NTDs are morphologically very similar to spontaneous NTDs.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7986388 TI - Diastematomyelia--clinical manifestation and treatment outcome. AB - Diastematomyelia is a rare congenital anomaly characterized by a division of the spinal cord or the filum terminale into two parts. In Korea, only one case has been reported. The authors have operated on 5 cases of diastematomyelia with septum since July, 1978. The ages ranged from 1 to 44 years (median; 11 years). There were 2 boys, 2 girls and an adult man. The disease manifested by cutaneous abnormalities and neurological or orthopedic deficits. Pain was a chief complaint in the adult patient. The symptoms had progressed in 3 cases. The diagnosis was made correctly by CT myelography or MRI in 4 cases. The median septum was located at the lumbar area in 4 cases and at the lumbosacral region in 1 case. Associated abnormalities included low lying conus (5 cases), lipoma (2 cases), thickened filum terminale (1 case), hemilipomyelomeningocele (1 case) and syrinx (1 case). The median septum was removed. The dural sleeve adjoining the septum was resected and the dural sac was reconstructed. The role of MRI in the diagnosis and planning of surgery and the high frequency of associated low lying conus were emphasized. Though the surgical treatment relieved pain, it did not reverse the neurological deficits or orthopedic deformities significantly, which suggests the beneficial effects of early surgical intervention in the cases with progressive symptoms. PMID- 7986387 TI - Cerebral energy metabolism following ESWL brain injury model and effects of cerebral protective drugs. AB - The goal of this study was to introduce a new method inducing an experimental brain injury model using ESWL(Extracorporeal Shock Wave Lithotripsy) and to evaluate findings of localized lesions on 1H MR imaging and the response of cerebral energy metabolism using a 31P MR spectroscope to the ESWL brain injury in cats. This study also examined effects of cerebral protective drugs. 1) There were no statistically significant changes in pH at all measurement points. 2) In the trauma group, initial decrease of PCr/Pi was seen at 30 to 60 minutes with return to control levels by 2 hours after injury(P < 0.05), followed by a second decline at 4 hours which lasted until 8 hours after injury. 3) Significant recovery in PCr/Pi(P < 0.05) was observed in both the THAM and dexamethasone treated groups at all measurement points and in the mannitol treated group only temporary recovery at 30 and 60 minutes (P < 0.05). 4) High intensity signals were seen on 1H MR imaging in traumatized animals. This study demonstrated the immediate and persistent recovery of cerebral energy metabolism using THAM or dexamethasone and an immediate but transient effect with mannitol in traumatized animals. PMID- 7986389 TI - A clinical study of benign focal amyotrophy. AB - We reviewed the clinical, electrophysiological, radiological, and histopathological findings in 25 patients with benign focal amyotrophy. There were 14 patients with upper limb type and 11 with lower limb type. 18 patients had unilateral involvement and 7 had bilateral involvement asymmetrically. The characteristics clinical features were sporadic occurrence, predominance in young males, nonprogressive course or initial progression for 1 to 3 years followed by stationary state, segmental distribution of muscle weakness and atrophy localized to one limb or both homologous limbs markedly asymmetrically, and absence of any definite sensory loss or central nervous system involvement. The electrophysiological, radiological, and muscle histopathological findings suggested chronic focal anterior horn cell disease. Although the prevalence of this disease is still unknown, the importance of recognition is being emphasized because of its common occurrence in our country and the benign prognosis. PMID- 7986390 TI - The tumor necrosis factor beta * 1 allele is linked significantly to HLA-DR8 in Koreans with atrophic autoimmune thyroiditis who are positive for thyrotropin receptor blocking antibody. AB - The localization and functional characteristics of tumor necrosis factor(TNF) beta gene raise the possibility that it may be involved in the susceptibility to autoimmune thyroid diseases. To investigate whether a TNF beta gene polymorphism is associated with autoimmune thyroiditis, we analyzed the TNF beta gene polymorphism with the restriction enzyme NcoI in 48 Korean patients with atrophic autoimmune thyroiditis [23 were found to be thyrotropin binding inhibitor immunoglobulin(TBII) positive, 25 TBII negative], 52 goitrous autoimmune thyroiditis, and 129 healthy controls. Two TNF beta alleles were identified from the restriction fragment length polymorphism studies of amplified genomic DNA. In atrophic autoimmune thyroiditis patients positive for TBII, 7 of 23 patients were homozygous for the TNF beta * 1 allele, 3 were homozygous for the TNF beta * 2 allele, and 13 were TNF beta * 1/2 heterozygous compared to controls(P = 0.20). Also, there were no associations between the TNF beta gene polymorphism and either TBII-negative atrophic autoimmune thyroiditis or goitrous autoimmune thyroiditis. Of the HLA-class II antigens, the frequency of HLA-DR8 was significantly greater among the 23 Korean patients with TBII-positive atrophic autoimmune thyroiditis compared to control subjects (Pc = 0.003). When the HLA DR8 positive patients with TBII-positive atrophic autoimmune thyroiditis and controls were analyzed separately, the DR8 positive patients with TBII-positive atrophic autoimmune thyroiditis had more homozygotes for the TNF beta * 1 allele(6/12, 50.0%) and no homozygotes for the TNF beta * 2 allele, as compared to the DR8 negative patients with TBII-positive atrophic autoimmune thyroiditis and DR8 positive controls(P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7986391 TI - Epstein-Barr virus associated posttransplant malignant lymphoma in renal allograft recipients. AB - We report two cases of posttransplant malignant lymphoma(PTML) of B cell origin associated with Epstein-Barr virus(EBV) infection. They were a 52-year-old male and a 37 year-old-female, in whom intermediate-grade diffuse malignant lymphomas of large cell type developed in the submandibular area and jejunum, respectively. DNA and RNA in situ hybridization revealed the presence of EBV-specific DNA and RNA sequences in the tumor cells. PMID- 7986392 TI - Growth hormone replacement therapy in adults with growth hormone deficiency; thrice weekly low dose administration. AB - Recent reports on growth hormone (GH) therapy have shown that GH has various beneficial effects in GH deficient adults. In most of these studies, GH was administered daily. Because GH is still expensive and has to be delivered by subcutaneous injection, we studied the 6-month therapeutic effects of thrice weekly GH injection therapy and compared it with daily therapy. Twenty eight adult patients with GH deficiency were randomly assigned into group 1 (ten cases, thrice weekly injections of GH), group 2 (nine cases, daily injections), and group 3 (nine cases, placebo injections). Lean body mass, serum basal GH levels, and insulin-like growth factor 1 levels significantly increased after six months of GH therapy in both groups 1 and 2. According to computed tomography, the mean mid-thigh muscle mass significantly increased in group 1, while the visceral fat mass significantly decreased in group 2. GH levels significantly increased exercise rate-pressure product and hand grip strength only in group 1. These results suggest that thrice weekly injections of GH are as effective as daily injections in GH deficient adults. PMID- 7986393 TI - The biologic role of ganglioside in neuronal differentiation--effects of GM1 ganglioside on human neuroblastoma SH-SY5Y cells. AB - Human neuroblastoma SH-SY5Y cell is a cloned cell line which has many attractive features for the study of neuronal proliferation and neurite outgrowth, because it has receptors for insulin, IGF-I and PDGF. Gangliosides are sialic acid containing glycosphingolipids which form an integral part of the plasma membrane of many mammalian cells. They inhibit cell growth mediated by tyrosine kinase receptors and ligand-stimulated tyrosine kinase activity, and autophosphorylation of EGF(epidermal growth factor) and PDGF receptors. The experiment was designed to study the effects of GM1 ganglioside on growth of human neuroblastoma SH-SY5Y cells stimulated with trophic factor in vitro. The cells were plated in Eagle's minimum essential medium without serum. The number and morphologic change of SH SY5Y cells were evaluated in the serum free medium added GM1 ganglioside with insulin or PDGF. SH-SY5Y cells were maintained for six days in serum-free medium, and then cultured for over two weeks in serum-free medium containing either insulin or PDGF. The effect of insulin on cell proliferation developed earlier and was more potent than that of PDGF. These proliferative effects were inhibited by GM1 ganglioside, and the cells showed prominent neurites outgrowth. These findings suggest that GM1 ganglioside inhibits the cell proliferation mediated by tyrosine kinase receptors and directly induces neuritogenesis as one of the neurotrophic factors. PMID- 7986394 TI - Esophageal duplication cyst complicated with intramural hematoma--case report. AB - Esophageal duplication cysts account for a very small percentage of benign esophageal tumors and are infrequently symptomatic. Esophageal duplication cysts result from aberrant alignment of the normal vacuolization process that produce the esophageal lumen in the 5th to 8th week of embryonic life. Complications most often are bleeding into or infection of cysts. Recently, we experienced a case of esophageal duplication cyst complicated with intramural huge hematoma and the cause of hematoma could not be identified. We report it with a review of literatures. PMID- 7986395 TI - Linear scleroderma occurring in a patient with systemic lupus erythematosus- short report. AB - A 38-year-old woman with systemic lupus erythematosus had developed a cutaneous lesion of linear scleroderma on the forehead 4 years after the diagnosis of lupus erythematosus. This case of coexistence of the two diseases can be regarded as a clinical variant of the connective tissue disease-overlap syndrome. PMID- 7986396 TI - A case of giant hemangioma of the liver presenting with fever of unknown origin. AB - A 37 year-old-woman was admitted to the hospital because of 15 days' duration of continuous fever. Routine studies for detection of fever foci were negative. Imaging studies revealed giant hemangioma of the liver with central thrombosis. The fever persisted for a period of 4 weeks, and subsided after conservative management. We report a case of hepatic hemangioma presenting with fever of unknown origin. The condition is very rare, but should be regarded as one of the causes of fever of unknown origin. PMID- 7986397 TI - Radiologic assessment in pulmonary lobar transplantation. AB - Pulmonary lobar transplantation provides a clue to the acute donor shortage. To examine the experimental and clinical applicability of lobar transplantation, the authors observed the extent of lung expansion and infiltrate in the allografted lobe through the sequential analysis of the early chest roentgenograms. MATERIALS AND METHODS: Twenty two mongrel dogs weighting 17 kg on average were used. Donor lung bloc was taken and flushed with Euro-Collins solution. The left lower lobar bloc was procured and implanted in the pneumonectomized recipient dog. The anastomosis was performed in the order of the pulmonary vein, artery, and bronchus. To assess the radiological pattern in the lobar allograft, a grading system was designed according to the extent of lung expansion and infiltrate. RESULTS: A) Expansion pattern: Good to excellent lung expansion was seen on postoperative day 0 in 6 out of 10 dogs; on day 1, 4/7; day 2, 3/12; day 3, 1/1; and day 4, 1/3, respectively. Radiographs on day 6, 7, and 12 also showed good expansion in one dog. B) Lung opacity pattern: Clear to minimal infiltrates were seen on day 0 in 8 out of 10 dogs; day 1, 7/17; day 2, 2/12; and day 4, 1/3. The same appearances were detected in a single dog on day 6, 7, and 12. C) Expansion opacity correlation pattern: Radiographs on postoperative day 0 showed good expansion with mild infiltrates, and excellent expansion with minimal infiltrates were observed on day 1 in 3 out of 17 dogs, day 2, 1/12; and day 4, 1/3, respectively.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7986398 TI - Zidovudine phosphorylation in HIV-infected patients and seronegative volunteers. AB - OBJECTIVES AND DESIGN: Measurement of phosphorylated zidovudine (ZDV) inside infected cells is more likely to provide satisfactory dose response relationships than serum concentrations. This study provides information on ZDV phosphorylation in HIV-seronegative volunteers (n = 5) and in patients with HIV infection (n = 12). METHODS: Intracellular ZDV phosphate metabolites were measured in peripheral blood mononuclear cells isolated from whole blood by density cushion centrifugation. Cells were washed and extracted overnight with 60% methanol prior to analysis by high performance liquid chromatography. Fractions eluted from the column corresponding to ZDV, ZDV monophosphate (ZDV-MP), ZDV diphosphate (ZDV-DP) and ZDV triphosphate (ZDV-TP) were collected, hydrolysed by acid phosphatase and ZDV levels quantified by radioimmunoassay. RESULTS: The area under the plasma ZDV concentration-time curve (AUC0-6 h) was similar in seronegative volunteers and patients [mean +/- SD, 4.64 +/- 2.50 versus 5.56 +/- 2.67 mumoles/l h; 95% confidence interval (CI), -4.39-2.23; P = 0.646, Mann-Whitney U test]. However, ZDV phosphorylation was greater in patients, with the AUC0-6 h for total phosphate metabolites being 5.91 +/- 3.42 pmoles/10(6) cells h compared with seronegative volunteers (0.66 +/- 0.48 pmoles/10(6) cells h; 95% CI, -8.35 to 2.32; P = 0.0003). The concentration of ZDV-TP was similar in both groups, the increase in total phosphates in patients being due primarily to ZDV-MP. ZDV-MP AUC0-6 h and total ZDV phosphate AUC0-6 h were closely correlated (r2 = 0.94). The relationship between total ZDV phosphate AUC0-6 h and the CD4 count demonstrates that patients with a count < 100 x 10(6)/l have much higher ZDV phosphate levels, predominantly ZDV-MP. CONCLUSION: ZDV is phosphorylated to a greater extent in patients than in healthy volunteers. The increased ZDV-MP in patients with low CD4 counts may explain the well known occurrence of increased ZDV toxicity in patients with more advanced disease. The ability to measure ZDV phosphorylated metabolites (without the administration of radiolabelled nucleoside) represents a significant advance in our understanding of the clinical pharmacology of the drug. PMID- 7986399 TI - Pathogenesis of AIDS lymphomas. AB - The AIDS-associated lymphomas represent a heterogeneous set of disease processes. The largest histologic subset of lymphomas is the large-cell lymphomas, which represent a spectrum of disease processes ranging from monomorphic monoclonal B cell proliferations to very polymorphic and polyclonal mixtures of B cells, T cells and macrophages. The next most frequent class of systemic lymphoma are the small non-cleaved cell or Burkitt's-like lymphomas. These are relatively monomorphic, monoclonal malignant B-cell proliferations. The final subset of lymphomas, which are likely to become more common as the AIDS epidemic progresses, are the primary CNS lymphomas, which are expansions of EBV immortalized B cells. The high incidence of tumor-associated EBV in the CNS lymphomas makes these lesions somewhat analogous to an opportunistic EBV infection. In HIV disease there is a long lag after infection before the appearance of clinical manifestations of impaired T-cell immunity. During this period, both appropriate B-cell proliferation in response to antigen (including the ubiquitous HIV) and abnormal B-cell proliferation (autoimmune, dysregulated) occur as the follicular architecture is disrupted by the virus and potential APC are exposed and/or infected with HIV. The destruction of FDC or the involution of their processes could interfere with the elimination by apoptosis of low-avidity B-cell clones. Antigen-competent B cells with pre-existing chromosomal translocations such as the t(8;14) (c-myc, IgH) would have a selective growth advantage in this setting. Figure 9 shows a schematic representation of prelymphomatous and lymphomagenic events as they are projected to occur. A similar pathogenetic scheme has been postulated for follicular B-cell lymphomas: PCR studies have demonstrated that a pool of t(14;18) (IgH;bcl-2) B-cells are present in lymph nodes featuring follicular hyperplasia. In response to antigen (the evidence favoring antigen drive is extensive hypersomatic mutation in sequences related to binding sites), B cells with the t(14;18) translocation have a selective advantage because the bcl-2 oncogene confers a resistance to apoptosis. Burkitt's lymphomas, particularly sporadic or HIV variants, fulfill at least the key criteria for antigen competence, mainly the presence of surface Ig. The c-myc-associated chromosomal translocational events are likely to occur early during the enzymatic machinations of gene rearrangement. Such B cells would be in the dysregulated cytokine and antigen milieu of HIV disease and ultimately could have a selective advantage. EBV infection of B cells probably requires activation and expression of the CD21 receptor. Furthermore, CD5+ B cells of CLL are refractory to EBV infection.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 7986400 TI - Male homosexual transmission of HIV-1. PMID- 7986401 TI - The immunosuppressive peptide of HIV-1: functional domains and immune response in AIDS patients. AB - OBJECTIVES: To study the biological properties of the immunosuppressive peptide (ISU-peptide) of HIV-1, a 17-mer corresponding to the amino-acid domain 583-599 of the transmembrane glycoprotein gp41 of HIV-1. This peptide exhibits sequence homology to the highly conserved ISU-peptide of type C and D retroviruses. Also, to study the immune response against the corresponding gp41 epitope in AIDS patients. DESIGN: The ISU-peptide and control peptides were synthesized and tested for immunosuppressive activity in different in vitro lymphocyte proliferation assays. Antibody responses were tested using a peptide enzyme linked immunosorbent assay. A new property of the ISU-peptide, inhibition of HIV 1 replication, was investigated using a cytopathogenicity assay. RESULTS: The ISU peptide of HIV-1 and the immunosuppressive peptides of type C and type D retroviruses possess similar functional properties. They inhibit mitogen-induced and lymphokine-dependent T-lymphocyte proliferation, they are interspecies reactive, they must be conjugated to a carrier protein in order to be immunosuppressive, and their N-terminal octamers represent the minimal immunosuppressive domain. HIV-infected individuals develop antibodies against an epitope located at the C-terminal end of the ISU-peptide and the number of responders and antibody titres decrease during progression to AIDS. In addition to its immunosuppressive activity, the ISU-peptide of HIV-1 inhibits the cytopathic effect of HIV-1 on human MT4 cells, suggesting interference with virus replication. CONCLUSIONS: The immunosuppressive property of the ISU-peptide suggests that gp41 might contribute to the development of AIDS. The evolutionary conservation of the immunosuppressive domain and the ability of the corresponding ISU-peptide to inhibit HIV replication suggest that this domain plays an important role in the life cycle of HIV-1. PMID- 7986402 TI - Clinical and immunological changes in AIDS patients following adoptive therapy with activated autologous CD8 T cells and interleukin-2 infusion. AB - OBJECTIVES: (1) To determine the safety and feasibility of repetitive reinfusions of activated autologous CD8 cells followed by low-dose continuous interleukin (IL)-2 infusion in patients with AIDS. (2) To study the relationships between clinical responses, surface marker phenotypic distributions and cytokine expression patterns of both cultured CD8 cells and lymphocytes in the peripheral blood compartment. DESIGN: Six adult patients with Centers for Disease Control and Prevention group IV HIV-1 disease ranging from mild to severe, were studied. All patients were receiving zidovudine prior to and during the study period, and had initial CD4 and CD8 cell counts > 50 and 200 x 10(6)/l, respectively. METHODS: Autologous CD8 T cells (10(8)-10(10)) were reinfused five times after ex vivo culture and stimulation with phytohemagglutinin and recombinant (r) IL-2. The fifth such infusion was followed by 5 days of rIL-2 infusion. Phenotypes and cytokine expression patterns of the expanded cells were determined as well as serum levels of immune mediators throughout the study. RESULTS: Patients showed stable CD4 and CD8 cell counts, p24 antigenemia, and minimal toxicity over the 24 week protocol study. Clinical improvement was observed in lymphadenopathy (six out of six), oral hairy leukoplakia (three out of four), and Kaposi's sarcoma (KS; two out of two) in the patients studied. In vivo induction of detectable levels of bioactive acid-stable interferon (IFN)-alpha, but not of other cytokines studied, upon activated CD8 cell reinfusion was associated consistently with improvement of oral hairy leukoplakia. However, partial regression of KS was observed after the CD8 cell infusion cycles and without IFN-alpha induction. In one of the two patients studied, KS regression was associated with decreased IL-1 alpha serum levels. In the other patient, who had failed previous IFN-alpha therapy, KS regression was observed after a decline in reinfused CD8 cell associated gene expression of tumor necrosis factor (TNF)-beta. Both IL-1 alpha and TNF-beta are growth factors for KS cells. CONCLUSIONS: These observations demonstrate the feasibility and safety of ex vivo CD8 cell activation, expansion, and reinfusion, and rIL-2 infusion in AIDS patients. The findings in this Phase I trial suggest potential clinical efficacy and encourage Phase II trials. The correlations obtained between clinical and immunological states could contribute to an understanding of the relationship between CD8 T-cell function and HIV-1 associated disease progression. PMID- 7986403 TI - Comparison of viral burden and phenotype of HIV-1 isolates from lymph nodes and blood. AB - OBJECTIVE: To compare the viral burden and the biological phenotype of HIV-1 isolates obtained from lymphoid node mononuclear cells (LNMC) and peripheral blood mononuclear cells (PBMC) in 11 HIV-infected patients. METHODS: Viral burden was quantified by cocultivating LNMC and PBMC from HIV-infected patients with PBMC from seronegative donors. For each patient, LNMC and PBMC isolates were characterized in terms of susceptibility to neutralizing antibodies, syncytium inducing capacity and sensitivity to zidovudine. RESULTS: Our data show that: (1) viral burden was 1.73 log higher in LNMC than PBMC in patients with persistent generalized lymphadenopathy and only 0.37 log higher in patients with AIDS related complex; (2) five out of 11 LNMC bulk isolates were phenotypically distinct from autologous PBMC isolates; (3) in three patients, the autologous serum neutralized the PBMC isolates but not the LNMC isolates. CONCLUSIONS: These results suggest that the relatively high level of HIV-1 replication in lymph nodes may favour the emergence of viruses exhibiting specific phenotypes, including neutralization escape variants. The existence of viral variants in lymphoid tissue at all stages of HIV infection may elucidate certain aspects of the pathogenesis of HIV-1 infection. PMID- 7986404 TI - Cross-neutralizing antibodies to HIV-1ANT70 and HIV-1IIIB in sera of African and Belgian HIV-1-infected individuals. AB - OBJECTIVES: To determine the neutralizing antibody patterns to HIV-1ANT70 (ANT70) and HIV-1IIIB (IIIB) in human sera obtained from HIV-1-infected individuals from different African countries and Belgium. Second, to correlate the presence of neutralizing antibodies in sera and their ability to bind to synthetic peptides derived from eight different HIV-1 V3 loop sequences. DESIGN AND METHODS: Forty sera from Belgium and 88 obtained from seven countries in Africa were tested for their ability to neutralize ANT70 (one of the most genetically divergent HIV-1 isolates documented), and IIIB. Sera found to cross-neutralize both viruses were further challenged with four HIV-1 field isolates. All sera were tested on a panel of V3 loop peptides obtained from different HIV-1 genotypes. RESULTS: Four patterns of sera were identified, including 33 (26%) sera not neutralizing any of the isolates, seven (5%) sera neutralizing only ANT70, 45 (35%) sera neutralizing only IIIB, and 43 (34%) sera cross-neutralizing both isolates. Sera capable of cross-neutralizing both ANT70 and IIIB consistently neutralized other field isolates tested, with a remarkable similarity in neutralizing antibody titre. A significantly higher number of sera cross-neutralizing both ANT70 and IIIB compared with sera lacking neutralizing antibodies, reacted simultaneously in enzyme-linked immunosorbent assays (ELISA) with three or more V3 loop peptides belonging to HIV-1 strains of different genotypes. However, none of the sera cross-neutralizing ANT70 and IIIB were reactive in ELISA with the ANT70 V3 loop peptide. CONCLUSION: These results suggest that despite pronounced genomic variation of the HIV-1ANT70 isolate, there are strongly conserved neutralizing epitopes situated outside the V3 loop that are shared by other HIV-1 isolates. These findings suggest that genetic variation might be surmountable in the design of a polyvalent HIV vaccine, if neutralizing antibodies are found to be correlates of protection in HIV infection. PMID- 7986405 TI - Dendritic cells persistently stimulate antibody responses to HIV in seropositive individuals. AB - OBJECTIVES: B-cell hyperactivity and hypergammaglobulinaemia with high levels of HIV-1-specific antibody occur during HIV-1 infection. We investigated the role played by antigen-presenting cells (APC) in the ongoing production of antibody. METHODS: Adherent monocytes and non-adherent low density dendritic cells were enriched from peripheral blood of patients at different stages of HIV-1 infection (Centers for Disease Control and Prevention categories II, III and IV) and from control subjects at high or low risk of HIV infection. Different concentrations of lymphocytes were cultured in 20 ml hanging drops in the presence or absence of autologous dendritic cells or monocytes. Antibodies to p24 and gp120 were assessed by enzyme-linked immunosorbent assay. RESULTS: Lymphocytes taken from asymptomatic HIV-1-seropositive subjects and depleted of APC produced low or moderate levels of antibody to gp120 or p24 in vitro. However, adding back autologous dendritic cells significantly enhanced antibody production, although fewer samples showed responses to p24 than to gp120. Less antibody production was stimulated using cells from patients with persistent generalized lymphadenopathy, or if monocytes rather than dendritic cells were added back. Little or no antibody was produced by cells from patients with AIDS and no antibody was detected in cultures of cells from seronegative individuals with low or high risk for infection. CONCLUSIONS: The evidence suggests that ongoing humoral responses to HIV-1 are fuelled by dendritic cells. Thus, the dominance of humoral over cell mediated responses in HIV-1 infection may depend upon signalling via dendritic cells. Changes in signalling by dendritic cells could be central to the immunologic features of HIV-1 infection. PMID- 7986406 TI - Effectiveness of supervised, intermittent therapy for tuberculosis in HIV infected patients. AB - OBJECTIVE: To evaluate the effectiveness of supervised therapy for tuberculosis (TB) in patients with HIV infection. DESIGN: Retrospective, chart review. PATIENTS: Patients with TB and HIV infection. SETTING: Urban, public TB clinic. MAIN MEASURES AND RESULTS: A total of 107 patients with TB and HIV infection were studied. Most were men (78%), African American (91%), uninsured or on Medicaid (88%), and 67% were injecting drug users. TB was diagnosed before AIDS in 31% of subjects, at the time of AIDS in 32%, and after AIDS in 37%. Clinical features varied by stage of HIV disease. Sixteen patients received no therapy and died before TB was diagnosed, 10 died during the first 8 weeks of treatment. Seventy eight patients received > 8 weeks therapy, of whom 48 (62%) were given directly observed therapy twice weekly and 30 (38%) received self-administered daily therapy. Patients who received directly observed therapy were more likely to complete 6 months of therapy (96 versus 76%, P = 0.02) and more likely to survive after therapy ended (85 versus 57%, P = 0.01). By logistic regression, directly observed therapy, AIDS diagnosed before TB, and age were significantly associated with survival outcome. CONCLUSION: Directly observed therapy for TB in patients with HIV infection is highly effective and associated with better adherence to therapy and survival. PMID- 7986407 TI - A phase I study of letrazuril in AIDS-related cryptosporidiosis. AB - OBJECTIVE: The intestinal parasite Cryptosporidium is a common cause of chronic diarrhoea in AIDS patients and is responsible for significant morbidity and mortality. No effective treatment is currently available for this condition. Here we aim to determine the safety, tolerance, and clinical effect of letrazuril in the treatment of AIDS-related Cryptosporidiosis. DESIGN: A prospective, open label study of letrazuril was performed. SETTING: The study was conducted at the Immune Deficiency Treatment Centre (IDTC) of Montreal General Hospital, a tertiary-care centre with inpatient and outpatient facilities. PARTICIPANTS: All HIV-positive patients presenting to the IDTC between November 1991 and January 1993 who had symptomatic intestinal Cryptosporidiosis were enrolled in this protocol. Sixteen participants entered the study and 15 were available for evaluation, having completed at least 2 weeks on the study medication. INTERVENTIONS: Patients received letrazuril daily in escalating doses of 50 to 100 mg orally for 6 weeks. Clinical and laboratory evaluations were performed weekly during the treatment phase, with a follow-up evaluation 4 weeks after the end of this phase, for a total study period of 10 weeks. MAIN OUTCOME MEASURES: Response to letrazuril was assessed by eradication of Cryptosporidial oocysts from the stool and symptomatic improvement in diarrhoea and abdominal pain. Haematological, biochemical, and electrocardiographic parameters were also studied to evaluate potential toxicities of the treatment. RESULTS: Fourteen evaluable patients had baseline CD4 lymphocyte counts ranging from 3 to 99 x 10(6)/l cells (mean, 30 x 10(6)/l cells). (The fifteenth evaluable patient had a CD4 count 235 x 10(6)/l.) Of these 14 patients, five showed a major response (symptomatic improvement and eradication of Cryptosporidial oocysts from the stool), two had a minor response (symptomatic improvement with persistence of oocysts in stool), and seven had no response to therapy with letrazuril. Seven patients developed a transient drug-related rash. CONCLUSION: Fifty per cent of the AIDS patients in this study experienced an improvement in their Cryptosporidial disease while receiving letrazuril. No serious dose-related toxicities were observed. Larger Phase II trials are needed to evaluate the safety and efficacy of letrazuril in AIDS-associated intestinal Cryptosporidiosis. PMID- 7986408 TI - Successful treatment of varicella zoster virus meningoencephalitis in patients with AIDS: report of four cases and review. AB - OBJECTIVE: Neurologic complications are common in patients with AIDS. Herpes zoster is a common early manifestation of HIV infection, but there have been few reports of encephalitic complications and nearly all have been postmortem. We report four cases of varicella zoster virus (VZV) meningoencephalitis diagnosed and treated antemortem, and briefly review the relevant literature. SETTING: Mount Zion Medical Center, San Francisco, California, USA. PATIENTS: Four HIV positive male patients with antibodies to VZV in their cerebrospinal fluid. INTERVENTION: Treatment with intravenous acyclovir (three cases) and intravenous ganciclovir (one case), which resulted in resolution of all symptoms except blindness in one patient. CONCLUSION: Antibodies to VZV in the cerebrospinal fluid of HIV-positive individuals may allow early diagnosis and lifesaving treatment of VZV meningoencephalitis. PMID- 7986409 TI - Reversible renal failure caused by a microsporidian infection. AB - OBJECTIVE: To report a case of renal failure associated with microsporidian infection in an HIV-seropositive patient. DESIGN: Case report. SETTING: Chelsea and Westminster Hospital, London, England, UK. PATIENT: An HIV-seropositive patient presented febrile with abdominal pain who developed renal failure. Renal biopsy and urinalysis showed infection with a microsporidian of the genus Encephalitozoon. INTERVENTION: Treatment with albendazole (400 mg) twice daily was associated with disappearance of infection from the urine, clinical improvement and return of renal function virtually to normal. CONCLUSION: HIV seropositive individuals with renal failure should have urine screened for microsporidia. The administration of albendazole in such cases may reverse renal failure. PMID- 7986410 TI - Long-term HIV-1 infection without immunologic progression. AB - OBJECTIVE: To identify and describe a subgroup of men infected with HIV for 10-15 years without immunologic progression, and to evaluate the effect of sexually transmitted diseases (STD) and recreational drug use on delayed HIV disease progression. DESIGN: Inception cohort study. SETTING: Municipal STD clinic. PARTICIPANTS: A total of 588 men with well documented dates of HIV seroconversion and 197 HIV-seronegative controls. MAIN OUTCOME MEASURES: AIDS, CD4+ count, rate of CD4+ cell loss, CD8+ count, beta 2-microglobulin, complete blood count, p24 antigen and HIV-related symptoms. RESULTS: Of 588 men, 69% had developed AIDS by 14 years after HIV seroconversion (95% confidence interval, 64-73%). Of 539 men with HIV seroconversion dates prior to 1983, 42 men (8%) were healthy long-term HIV-positives (HLP), HIV-infected > or = 10 years without AIDS and with CD4+ counts > 500 x 10(6)/l. When compared with progressors (men with HIV seroconversion prior to 1983 but with AIDS or CD4+ counts < 200 x 10(6)/l), HLP had a significantly slower rate of CD4+ decline (6 versus 85 x 10(6)/l cells/year), and less abnormal immunologic, hematologic and clinical parameters. However, when compared with HIV-uninfected controls, HLP demonstrated lower CD4+ counts and mild hematologic abnormalities. There were no consistent differences between HLP and progressors in prior exposure to recreational drugs or STD. CONCLUSION: There are individuals with long-term HIV infection who appear clinically and immunologically healthy 10-15 years after HIV seroconversion, with stable CD4+ counts. Lack of exposure to STD or recreational drugs does not appear to explain the delayed course of disease progression in HLP. PMID- 7986411 TI - Validation of the proposed World Health Organization staging system for disease and infection in a cohort of intravenous drug users. AB - OBJECTIVE: To assess the prognostic utility of the clinical criteria of the World Health Organization's (WHO) proposed staging system for HIV disease and infection in a cohort of intravenous drug users (IVDU) from the ALIVE study. METHODS: All study subjects known to be HIV-seropositive were included in this analysis. Subjects were classified as WHO clinical stage 1, 2, or 3 at their initial seropositive evaluation. Product-limit estimates and Cox proportional hazard models were used to compare time of progression to AIDS (stage 4) for the first three clinical stages. RESULTS: Of the original cohort of 2921 IVDU in the ALIVE study, 694 were known to be HIV-positive by January 1992. At the time of their index visit, 49% of the cohort were WHO clinical stage 1, 10% stage 2 and 41% were stage 3. Demographic characteristics of the three groups were similar. Product-limit estimates for progression to AIDS over a 3-year period were 6.5% (SE, 1.5%), 10.4% (SE, 4.1%) and 17.1% (SE, 2.5%) for clinical stages 1, 2, and 3, respectively (log-rank P = 0.003). In a proportional hazards model adjusting for race, age, sex and injection status within 6 months prior to enrollment, the hazard for progression to AIDS was 1.51 [95% confidence interval (CI), 0.60-3.77] and 2.39 (95% CI, 1.40-4.08) for stages 2 and 3, respectively, relative to stage 1. CONCLUSION: This study, in a population of IVDU, supports the utility of the WHO staging system in predicting progression from HIV seropositivity to AIDS on the basis of clinical signs and symptoms. PMID- 7986412 TI - Changes in blood transfusion practices after the introduction of consensus guidelines in Mwanza region, Tanzania. AB - OBJECTIVE: To assess the effect of introducing consensus guidelines on avoidable blood transfusions in Mwanza region, Tanzania. METHODS: Avoidable blood transfusions were determined among 842 blood transfusion recipients in eight hospitals in 1991. In a workshop with senior health workers from the region, consensus guidelines for the prescription of blood transfusions were developed and introduced in the hospitals and after 7 months intervention data were collected on 1042 blood transfusion recipients. The 1991 and 1992 data were compared to estimate the change in the proportion of avoidable blood transfusions. RESULTS: In blood transfusion recipients aged < 5 years there was a significant reduction in the proportion of avoidable blood transfusions from 257 (52%) out of 498 to 197 (33%) out of 595 (P < 0.001), especially at the peripheral hospitals. For children the proportion decreased from 25 to 17% (P < 0.05) and for operated patients the percentage remained at 24%. In pregnant women there was a significant increase in the proportion of avoidable blood transfusions from 10 to 27% and in adults from 37 (25%) out of 146 to 121 (50%) out of 242. The improvement in peripheral hospitals was offset by a similar deterioration in the referral hospital, thus no overall reduction was achieved in the proportion of avoidable blood transfusions. CONCLUSION: The development and introduction of consensus guidelines was not sufficient to change prescribing practice. The proportion of avoidable blood transfusions decreased only in hospitals where compliance was maintained through regular clinic meetings and strict supervision by senior medical staff. PMID- 7986413 TI - Injecting drug use and HIV infection in southwest China. AB - OBJECTIVES: To determine the prevalence of drug injection among drug users, the seroprevalence of HIV and risk factors for HIV infection among injecting drug users (IDU), and to determine heterosexual transmission of HIV among IDU and their spouses in southwest China. METHODS: Using a cross-sectional design, we conducted an HIV seroprevalence and behavioral survey in three rural counties of Yunnan province, Ruili, Longchuan and Luxi in southwest China, bordering Myanmar (Burma). A total of 860 drug users were recruited in randomly selected communities at the three study sites (response rate, 97%). In addition, a random sample of 62 wives of HIV-infected IDU were assembled from 460 known HIV-positive IDU in Ruili and Longchuan (response rate, 81%). RESULTS: In the sample of 860 drug users, 33% reported injecting drugs. Among the 282 subjects who injected drugs, 82% began intravenous drug use after 1988; 64% injected drugs at least once every day. All subjects shared needles but none cleaned the injection equipment with alcohol or bleach. Overall, 49% tested HIV-positive. HIV seropositivity was independently correlated with a longer history of drug injecting, daily injecting, frequent needle-sharing, being younger, and living in Ruili county. Among the 62 wives of HIV-positive IDU, none used condoms during sex and 10% tested HIV-positive. CONCLUSIONS: We conclude that the introduction of HIV into drug-using communities and the rapid increase in heroin injecting in this population appear to have triggered an explosive HIV epidemic among IDU in southwest China. We recommend that AIDS prevention efforts should begin immediately and focus on discouraging the shift from opium smoking to heroin injecting, needle-sharing, and unprotected sex among drug users and their partners. PMID- 7986414 TI - Levels of HIV testing and low validity of self-reported test results among alcoholics and drug users. AB - OBJECTIVES: To evaluate HIV testing behavior, validity of self-reported serostatus, and intention to test among alcoholics and drug users entering treatment. DESIGN: Longitudinal cohort study. METHODS: A total of 952 clients voluntarily entering three outpatient and two inpatient public alcohol treatment centers in San Francisco were enrolled. Seventy-six per cent were men, 50% black, 81% had used both alcohol and drugs during the last year, 43% had injected drugs and 9% of the men were homosexual. Subjects completed an interviewer-administered questionnaire and blindly-linked HIV-antibody test at entry and after 1 year (81% follow-up). RESULTS: Fifty-seven per cent of subjects reported that they had previously sought HIV testing. Factors associated with HIV testing included homosexual contact, injecting drug use, having a partner who had been tested, and using condoms. Hispanics were the least likely of all ethnic groups to report testing. Of 60 subjects with HIV antibodies, 47 (78%) said they had already been tested; however, 19 (40%) inaccurately reported that their serostatus was negative and another four (9%) had no collected their test results. Blacks were much more likely than other groups to misreport or be unaware of their HIV status. Only half of the 68% who said they planned to be tested during the following year did so. Five (42%) out of 12 HIV-positive individuals who were unaware of, or misreported their serostatus at baseline, and who sought another HIV test during the follow-up year continued to report themselves as uninfected. CONCLUSIONS: A large proportion of clients attending public alcohol treatment centers report having been HIV tested, much greater than that observed in other populations. However, misreporting of HIV test results was very common among seropositive subjects. Alcohol and drug treatment programs for this high-risk population should include interventions to optimize use of HIV testing for prevention and treatment, and improve understanding of test results. PMID- 7986416 TI - Changes in AIDS incidence trends in Spain. AB - OBJECTIVE: To detect changes in the evolution of the AIDS epidemic in Spain. DESIGN: Analysis of time-trends in AIDS incidence. METHODS: AIDS cases reported in Spain up to December 1993 were adjusted for reporting delays. Quarterly time trends in incidence were analysed for groups divided according to sex, age and transmission category. RESULTS: The adjusted number of cases diagnosed by September 1993 totalled 24,519. Of these, 15,652 were injecting drug users (IDU), 3679 were homosexual/bisexual men and 1753 were cases of heterosexually transmitted infection since 1989. AIDS incidence has exhibited a linear rate of growth. While all groups studied showed an upward trend, variations were found between the different groups. The overall trend resembled the pattern for IDU, the largest but the slope in the growth curve for this category has steepened steadily, and experienced the greatest percentage increases since 1989. AIDS incidence among blood transfusion recipients has risen slowly since 1988, while that for blood factor recipients reached a ceiling in 1989 and has declined progressively thereafter. Within the respective transmission categories, women exhibited trends similar to men. From 1989 onwards, a greater rate of increase was observed among those aged over 30 years than among those under 30. CONCLUSION: The overall trend in AIDS incidence is the sum of the epidemics in the different population groups. While advances in controlling the epidemic have been made in certain groups, the trend as a whole has worsened. PMID- 7986415 TI - AIDS education for primary school children in Tanzania: an evaluation study. AB - OBJECTIVE: To test the effects of an HIV/AIDS education program. DESIGN: A quasi experimental, nested cross-sectional design including baseline and 6-month follow up surveys. Schools, stratified according to location, were randomly assigned to intervention (n = 6) or comparison conditions (n = 12). SETTING: Public primary schools in Arusha and Kilimanjaro regions, Tanzania. PARTICIPANTS: A total of 2026 sixth and seventh grade pupils (average age, 14.0 years) participated at baseline (85%) and 1785 at follow-up. INTERVENTION: The program was designed to reduce children's risk of HIV infection and to improve their tolerance of and care for people with AIDS. Local teachers and health workers attended a 1-week training workshop before implementing the program over a 2-3-month period (averaging 20 school hours per class). MAIN OUTCOME MEASURES: Self-reported exposure to AIDS information, communication regarding AIDS; AIDS knowledge, attitudes towards people with AIDS, attitudes towards having sexual intercourse, subjective norms regarding sexual intercourse, and intention to engage in sexual intercourse. RESULTS: Following this program, intervention pupils reported significantly higher scores for the following outcome measures than pupils attending the comparison schools: AIDS information (13.1 versus 10.5; P = 0.0001), AIDS communication (10.9 versus 7.8; P = 0.0001) AIDS knowledge (14.5 versus 11.5; P = 0.0001), attitudes towards people with AIDS (9.0 versus 6.7; P = 0.0008), subjective norms (45.5 versus 43.9; P = 0.011), and intention (1.3 versus 1.4; P = 0.020). No program effect was seen for attitudes towards sexual intercourse (47.0 versus 46.3, P = 0.44). CONCLUSIONS: These results indicate that it is feasible and effective to provide AIDS education for Tanzanian primary school children. PMID- 7986417 TI - Bed occupancy due to HIV/AIDS in an urban hospital medical ward in Uganda. AB - OBJECTIVE: To determine the proportion of patients with HIV-related illness admitted to a medical ward. DESIGN: A prospective study. SETTING: Rubaga Hospital, the third largest hospital in Kampala, the capital of Uganda. PARTICIPANTS: A total of 449 patients admitted to the medical ward between September and November 1992. RESULTS: Of the 449 patients, 390 (86.8%) agreed to provide a blood sample for HIV serology. Of these, 55.6% (95% confidence interval, 50.7-60.5%) were positive for HIV. Eighty-six (22.2%) of all patients [71 (33%) of the seropositives and six (3.5%) of the seronegatives] met the World Health Organization case definition for AIDS in Africa. The HIV-seropositives had a mortality rate of 17.4%, significantly higher (P = 0.00057) than the 5.8% rate observed in the seronegative group. The overall mortality rate was 13.7% and was significantly associated with HIV infection (P = 0.0005). CONCLUSION: HIV infection is a major contributor to morbidity and mortality in Uganda. Over 50% of the medical admissions were HIV-positive revealing the serious impact of HIV on the health-care system. PMID- 7986418 TI - AIDS incidence rates in Europe and the United States. AB - OBJECTIVE: To facilitate the quantitative comparison of AIDS incidence statistics between countries and with other diseases using statistics based on age standardized incidence rates instead of absolute number of cases. DESIGN: AIDS incidence rates for 19 countries belonging to the World Health Organization (WHO) European region, and for comparative purposes, the United States. METHODS: Incidence rates were standardized using the world standard population for all ages, from 1985 to 1992. The data were derived from the WHO European Non Aggregate AIDS Dataset and the Centers for Disease Control and Prevention (CDC) AIDS Public Information Dataset, adjusted for reporting delays in each country. RESULTS: The AIDS incidence rate for men (81 in 1,000,000) in the United States was fourfold higher than the highest rate in a European country (Switzerland) in 1985; incidence rates in all other European countries, except France and Denmark, were below 10 in 1,000,000. Subsequently, AIDS incidence has increased more rapidly in southern Europe than in the rest of the continent. The estimated incidence rate for men in Spain (243 in 1,000,000) approached that in the United States (304 in 1,000,000) in 1992, and three additional countries (France, Switzerland and Italy) showed rates above 100 per million. The spread of the AIDS epidemic among women in some southern European countries was faster than in the United States. In Switzerland and Spain the standardized incidence rates in women were higher than in the United States by 1988 and 1992, respectively. CONCLUSIONS: Analysis trends in incidence rates avoids some weaknesses of AIDS statistics based on absolute numbers, and should become one of the standard tools for AIDS surveillance. PMID- 7986419 TI - Microsporidia cause human disease: evidence by subtraction. PMID- 7986420 TI - The European-Australian Collaborative Group Study 017 of zidovudine versus placebo. PMID- 7986421 TI - In situ polymerase chain reaction amplification: applications and current limitations. PMID- 7986422 TI - Diagnosis of central nervous system toxoplasmosis in AIDS patients confirmed by autopsy. PMID- 7986423 TI - Fatal Psychrobacter immobilis infection in a patient with AIDS. PMID- 7986424 TI - Estimation of the number of HIV-seropositive patients known to general practitioners in France. PMID- 7986425 TI - Persistent anaemia in HIV-infected individuals due to parvovirus B19 infection. PMID- 7986427 TI - Female street prostitution in Liverpool. PMID- 7986426 TI - Pentoxifylline preferentially inhibits interleukin-10 production by HIV-1 infected human T cells. PMID- 7986428 TI - A new class of substituted 1,2,4-triazolo-1,3,4-thiadiazepines. AB - A series of 3-aryloxymethyl-(5-nitro-2-furyl)-6-phenyl-1,2,4- triazolo[3,4 b][1,3,4]thiadiazepine compounds have been synthesized recently by a new route. Reported here are the structures of two such compounds with para-substituted aryloxymethyl groups: one has a chloro group, 3-(4-chlorophenyl-oxymethyl)-8-(5 nitro-2-furyl)-6-phenyl-1,2,4- triazolo[3,4-b][1,3,4]thiadiazepine, C22H14C1N5O4S, TD1, and the other a methyl group, 3-(p-tolyloxy-methyl)-8-(5 nitro-2-furyl)-6-phenyl-1,2,4- triazolo-[3,4-b][1,3,4]thiadiazepine, C23H17N5O4S, TD7. The nitrofuryl and phenyl groups on the thiadiazepine ring are each found to adopt a similar conformation in the two structures, whereas the aryloxymethyl substituents on the triazole rings are conformationally different from each other. Each thiadiazepine ring adopts a boat conformation with the S atom at the apex. The interplanar angle between the triazole ring and the thiadiazepine ring is 30 degrees for both compounds. The conformation of the aryloxy-methyl group is dependent on the intermolecular interactions that arise as a result of the polarity of the para substituent. The Cl group in TD1 is involved in a C-Cl...O non-bonded interaction with a Cl...O distance of 3.100 (3) A and a C-Cl...O angle of 138.4 (1) degree. TD7 has a stacking interaction involving the nitrofuryl groups. PMID- 7986429 TI - DCMCIT, an analogue of the antitumour drugs mitozolomide and temozolomide. AB - The crystal structure of 3-(2-chloroethyl)-N,N-dimethyl-4-oxo-3,4 dihydroimidazo[5,1-d]-1,2 ,3,5- tetrazine-8-carboxamide, (1), C9H11C1N6O2, an analogue of the novel bicyclic antitumour agents mitozolomide (2) and temozolomide (3), has been determined at 290 K. Although, as in structures (2) and (3), the imidazotetrazinone ring system is essentially planar, the substitution of the--CONH2 group at C8 by a--CON(CH3)2 group in (1) negates the possibility of forming an intramolecular hydrogen bond at either N7 or N1 and thus allows rotation of this group about the C8-C81 bond by ca 45 degrees. PMID- 7986430 TI - 2'-hydroxy-5,9-dimethyl-2-(3-methyl-2-butenyl)-6,7-benzomorphan (pentazocine) hydrochloride hydrate. AB - The title compound [1,2,3,4,5,6-hexahydro-6,11-dimethyl-3-(3-methyl-2-butenyl) 2,6-methano- 3- benzazocin-8-ol hydrochloride hydrate, C19H28NO+.-Cl-.1/8H2O, (I)] crystallizes with two molecules per asymmetric unit. A comparison of the bond lengths and torsion angles shows a side-chain orientation similar to that of cyclazocine but unlike that of naloxone. The two molecules are linked through a hydrogen-bond network to the interlayer Cl ions, forming a linear chain extending along the ac diagonal of the unit cell. PMID- 7986431 TI - Disinfectant storage media and composite/metal bond strength. AB - PURPOSE: To evaluate the effect of three disinfection procedures on the tensile bond strength of Panavia resin composite cement. MATERIALS AND METHODS: Alloy cylinders were bonded and stored in: (1) 0.2% chlorhexidine; (2) 2% activated glutaraldehyde; (3) distilled water and sterilized with ethylene oxide; and (4) distilled water. Solutions were monitored for bacterial cultures and pH changes regularly for 90 days after which all samples were tested to tensile failure. RESULTS: ANOVA showed no significant difference between mean group bond strengths. A direct positive correlation was demonstrated between solution pH and bond strengths (r = 0.98). All groups were found to represent effective methods for preventing bacterial growth in storage solutions during long term cement bonding studies. PMID- 7986432 TI - Microleakage of resin composites with wet versus dry bonding. AB - PURPOSE: To evaluate the effects of wet and dry bonding on microleakage of Class V composite restorations. MATERIALS AND METHODS: Cavity preparations were made in the buccal and lingual surfaces of 25 extracted human third molars. Half of each preparation was in enamel and the other half was in cementum/dentin. The preparations were randomly assigned to five groups for bonding with Scotchbond Dual-Cure (control), Scotchbond Multi-Purpose, or All-Bond 2. Scotchbond Multi Purpose and All-Bond 2 were applied using both wet and dry techniques. All preparations were restored with a microfill composite after bonding. The specimens were thermocycled 300 times between 5 degrees and 55 degrees C and were subjected to a silver nitrate staining technique to detect marginal leakage. RESULTS: Specimens bonded with All-Bond 2 and Scotchbond Multi-Purpose had significantly less leakage than the control. However, there was no statistically significant difference between wet and dry bonding techniques for either material. PMID- 7986433 TI - Penetration of a dentin bonding agent into dentin. AB - PURPOSE: To examine how the priming agents of Scotchbond Multi-Purpose (SMP) influenced the wettability of collagen in the demineralized zone and hence the penetration and adaptation of its bonding monomers. MATERIALS AND METHODS: Freshly extracted bovine teeth were ground to dentin with SiC paper. SMP and Z100 resin were used. Shear bond testing was performed as well as scanning electron microscopic evaluation. RESULTS: In contrast to the manufacturer's instructions, a 26.3% increase in shear bond strength was obtained when a second coat of priming agent was applied. This increase was statistically significant at the 5% level of confidence. SEM examination of failed conventionally air dried (CAD) specimens showed the presence of voids in the demineralized layer. SEM examination of failed specimens prepared by a critical point drying (CPD) technique showed that these voids were filled with collagen fibrils. The CPD technique also clearly showed that collagen fibrils were incorporated in the unfilled resin. Although priming agents appear to facilitate the penetration of unfilled resin into the demineralized layer and the dentin tubules, areas of unincorporated collagen fibrils can be seen even after two or more applications of the priming agent. PMID- 7986434 TI - Laboratory evaluation of the A.R.T. bonding system. AB - PURPOSE: To determine (1) the in vitro shear bond strengths of the A.R.T. Bond System to dentin at different time intervals, (2) the quantitative microleakage of Class V preparations in dentin restored with the A.R.T. Bond System, and (3) the resin penetration into the dentin tubules by scanning electron microscopy. MATERIALS AND METHODS: The occlusal surfaces of 75 extracted human mandibular and maxillary permanent first and second molars were ground wet on 600-grit SiC to expose the superficial dentin. The A.R.T. Primer and the A.R.T. Adhesive were applied to demarcated bonding sites as recommended by the manufacturer. Brilliant Dentin resin composite was transferred to the opening in a split Teflon mold in the assembly apparatus in three increments, each compressed firmly and cured for 40 seconds. Fifteen specimens were disassembled 60 seconds after final cure and then tested. The remaining 60 teeth were disassembled 15 seconds after cure; one group was tested at this time and the others immersed in saline at 37 degrees C for 24 hours, 1 week and 4 weeks before being tested. A shear load was applied at a crosshead speed of 0.5 mm/minute, the shear bond strengths calculated and expressed in MPa. Data were analyzed by ANOVA and Student Newman-Keuls test. Class V cavities were prepared at the facial surfaces of 18 extracted human permanent premolars and restored. Microleakage was determined quantitatively by a spectrophotometric dye-recovery method and expressed as mg dye/restoration. RESULTS: Mean +/- SD of the shear bond strength in MPa were 13.07 +/- 3.59 (1 minute), 16.08 +/- 3.12 (15 minutes), 18.17 +/- 3.44 (24 hours), 17.54 +/- 5.35 (1 week), 17.90 +/- 2.61 (4 weeks). The mean +/- SD microleakage was 0.008 +/- 0.04 mg dye/restoration. PMID- 7986435 TI - Effect of a silane coupling agent on composite repair strengths. AB - PURPOSE: To evaluate the use of a silane coupling agent (Silane Bond Enhancer) for repair of a glass-filled hybrid resin composite (Herculite XR). MATERIALS AND METHODS: Composite specimens (n = 20) were either air-abraded (AA) with an intraoral sandblaster (Microetcher), etched with 9.6% hydrofluoric acid (HF) (Porcelain Etch Gel), or treated with both methods (AA/HF). A silane coupling agent was applied to half of the specimens after these initial surface treatments. Composite repairs were completed by application of a phosphonate ester bonding agent (Bondlite) and resin composite (XRV Herculite). Transverse strengths of repaired specimens and intact (control) specimens were determined using an Instron. RESULTS: The mean bond strengths of repaired specimens ranged from 41% to 62% of the composite's cohesive strength. All repair strengths were significantly lower than the cohesive strength, but were not significantly different from each other. Silanation slightly improved the transverse strength of specimens repaired using the HF and AA/HF methods, but not those repaired using the AA procedure. PMID- 7986436 TI - Glass ionomer cement surface protection. AB - PURPOSE: To evaluate the effectiveness of various surface treatments for glass ionomer cement (GIC) by determining quantity of dye uptake spectrophotometrically. MATERIALS AND METHODS: Sixty specimens, 4.5 mm diameter and 2 mm thick, were made from Shofu GIC and divided into 10 groups. Positive control (A) and negative control (B) specimens were not protected while experimental specimens were protected with ARM chemically-cured bonding resin (C), Durafill Bond light-cured bonding resin (D), Bondlite light-cured bonding resin (E), Colorama nail varnish (F), Shofu varnish (G), Copalite varnish (H), Vaseline (I) or Vaseline followed by Copalite (J). The discs were immersed in 0.05% methylene blue solution 10 minutes after mixing except group B specimens which were immersed in deionized water. After 24 hours the discs were removed, washed, and individually placed in 1 ml 65% nitric acid for 36 hours. The solutions were filtered, centrifuged and the absorbance determined spectrophotometrically at 590 nm. Dye uptake was expressed in microgram dye/restoration and the data analyzed by ANOVA and Tukey Kramer test. RESULTS: The mean (SD) of dye uptake were: A:95.12 (11.28); B:0 (0); C:40.90 (5.06); D:33.89 (3.63); E:35.73 (3.36); F:3.29 (0.79); G:14.87 (2.86); H:21.99 (3.25); I:47.21 (7.06); J:29.74 (3.49). All the surface agents were effective in protecting setting restorative glass ionomer cement, but nail varnish provided the best results. PMID- 7986437 TI - Clinical evaluation of a posterior resin composite: 3-year results. AB - PURPOSE: To clinically evaluate a resin composite. MATERIALS AND METHODS: Sixty restorations were inserted at a ratio of 1:3 in Class I and II preparations in molars. Caulk Prisma AP.H/Prisma Universal Bond resin composite restorative system was placed. All the restorations were evaluated using the USPHS system and M-L indirect scale; 6, 12, 24 and 36 month recalls were compared to baseline. RESULTS: Color, interfacial staining, secondary caries, marginal integrity and surface texture (Alfa = 89%, 94%, 97%, and 100% respectively) were essentially unchanged from baseline for all restorations. One restoration failed due to secondary caries. Two were assessed with Charlie (C) ratings for marginal defects and one for wear. Direct wear analysis (Alfa = 12%) was significantly changed from the baseline. Indirect mean estimated wear measurements for each recall period, adjusted for baseline, were 21 +/- 18 microns, 54 +/- 29 microns, 67 +/- 29 microns, and 98 +/- 43 microns respectively. The wear of AP.H was characteristically linear (g2 = 0.987) for composites whose mean filler particle size approaches 1 micron or less. PMID- 7986438 TI - Laboratory evaluation of experimental restorative systems containing 4-META. AB - PURPOSE: To determine the in vitro shear bond strengths and quantitative microleakage of four experimental bonding restorative systems used in conjunction with Metafil-A, an experimental composite that does not contain 4-META, and Metafil-Ex, a 4-META containing experimental composite. MATERIALS AND METHODS: 120 test specimens were prepared on dentin treated with Amalgambond Activator followed by the application of an experimental primer consisting of 35% glyceryl methacrylate. In 60 teeth the mixed Amalgambond Base and Catalyst was then applied while in the remaining 60 teeth this step was omitted. Cylinders of either Metafil-A or Metafil-Ex were bonded to the dentin surfaces and the test specimens removed from the assembly apparatus after 1 minute or after 15 minutes and the latter specimens were stored in saline at 37 degrees C for 24 hours prior to determining the shear bond strength in an Instron machine at a crosshead speed of 0.5 mm/minute. Sixty Class V preparations were made on the facial surfaces of the roots of extracted human premolars and the preparations restored with the four restorative systems. The quantitative microleakage was determined by a spectrophotometric dye-recovery method. RESULTS: The shear bond strengths were significantly lower when the 4-META-containing Amalgambond Base and Catalyst were not applied and were unmeasurable when Metafil-A was used as the composite. The quantitative microleakage of the latter system was significantly greater than when the other restorative systems were used. PMID- 7986440 TI - Sterilization efficacy of a forced-air, dry heat sterilizer. AB - PURPOSE: To evaluate forced-air, dry heat sterilizer and test its ability to kill spores of Bacillus subtilis during both available cycles using packaged and unpackaged instruments. MATERIALS AND METHODS: A standard set of six orthodontic instruments were processed unpackaged through replicate 6-minute cycles with spore-strips on the top and bottom of each instrument. The spore strips were analyzed by culturing in Trypticase-soy broth for 7 days at 37 degrees C. RESULTS: No sterilization failures from properly placed spore-strips were detected in any of the 18 replicate cycles. Measurements of temperatures at three chamber sites during these cycles yielded only two of 36 instances when any portion of the chamber was at a temperature below the set temperature; however, no sterilization failures occurred during either of the two cycles involved. Also, a set of four orthodontic pliers were packaged and processed through replicate 12-minute cycles with spore-strips placed inside and attached to the outside of each package. None of the total 144 spore-strips processed through six replicate cycles showed growth after culture analysis. The study demonstrated sterilization efficacy for both the wrapped and unwrapped instrument cycles using biological indicators typically used to monitor dental office sterilizers. PMID- 7986439 TI - Clinical and laboratory evaluation of adhesive restorative systems. AB - PURPOSE: To investigate the effectiveness of Clearfil Liner Bond, Gluma 2000, and Scotchbond Multi-Purpose when applied in combination with proprietary restorative resins in V-shaped circular cavities which were cut in incisors either centrally on the labial enamel surface (Type 1) or labially crossing the cemento-enamel junction (Type 2). MATERIALS AND METHODS: Forty teeth scheduled for extraction for periodontal reasons were treated in vivo and another 40 teeth in vitro. The in vivo restored teeth were extracted after 3 months of clinical service and the in vitro treated samples were stored in water for 1 week and thermocycled 250 times between 5 degrees C and 55 degrees C, prior to a 24-hour immersion in 0.5% fuchsin tracer solution of all specimens, sectioning and scoring interfacial dye penetration. RESULTS: ANOVA revealed no significant differences between all in vivo samples sites, all in vitro enamel sites and the apical Type 2 sites of the Gluma samples. In contrast, the apical Type 2 leakage of CLB and SMP was significantly more pronounced, although not statistically different from each other. The results of the short-term clinical performance of the three systems was moderately more favorable than the laboratory microleakage test results. PMID- 7986441 TI - Causes and remedies for broken appointments. PMID- 7986442 TI - Marginal adaptation of the Concept inlay system. AB - PURPOSE: To evaluate the fit of the Concept inlay system in three clinically relevant cavity preparations (an occlusal, MO and MOD). MATERIALS AND METHODS: The processed inlays were adjusted as needed and seated on master dies. The greatest marginal discrepancy occurring along each margin was recorded and evaluated. RESULTS: The majority of the margins exhibited gaps in the range of 20 45 microns (statistically insignificant) with the exception of the distal margin of the MO which averaged approximately 80 microns and the buccal and lingual margins of the MOD which were approximately 70 microns (both statistically larger than the 20-45 microns range). This heat and pressure cured composite inlay system is capable of producing fairly closely fitting restorations. PMID- 7986443 TI - Subgingival irrigation with amine fluoride-stannous fluoride gel in treated periodontal pockets. AB - PURPOSE: To evaluate the long-term effect of subgingival irrigations with amine fluoride mixed with stannous fluoride on the repopulation of bacteria in deep periodontal pockets (> 5 mm) following the active phase of non-surgical mechanical treatment. MATERIALS AND METHODS: A split-mouth design was utilized in eight periodontal patients and the effect of the treatment was evaluated by microbiological culturing and clinical parameters. RESULTS: Slight reduction in total anaerobe counts were detected in both treated and control sides, up to the first 5 weeks, followed by an increase in the counts reaching a plateau after 30 weeks. In contrast, black-pigmented bacteroides species (BPB) were significantly suppressed in the treated sides as compared to the control sides over the whole study period. The difference between the clinical parameters and between the tested and control sides, although in some points were found to be statistically significant, seem to have no clinical significance. The use of amine fluoride stannous fluoride gel for irrigations of deep periodontal pockets as an adjunctive to conventional treatment, can prevent the repopulation of the pockets by BPB, which are considered to be a major group of periodontal pathogens. PMID- 7986444 TI - Laboratory evaluation of Amalgambond and Amalgambond Plus. AB - PURPOSE: To evaluate the shear bond strength (SBS) of a microfilled resin restorative material and an amalgam alloy to dentin using the Amalgambond Plus adhesive system with a variety of bonding regimens. MATERIALS AND METHODS: The study design incorporated bonding composite to both dry and moist dentin using open-ended plastic matrices and closed-ended gelatin capsules. In addition, the bond strength of amalgam to dry dentin was determined. RESULTS: The mean SBS of Silux Plus to dentin using Amalgambond without the HPA powder ranged from 17.55 +/- 1.96 MPa to 22.47 +/- 3.89 MPa. The SBS range observed when the microfilled composite was bonded to dentin with Amalgambond Plus (includes the HPA powder) was from 20.33 +/- 3.84 MPa to 22.50 +/- 3.69 MPa. There was no significant difference (P > 0.05) in the SBS of the microfilled resin restorative material to dentin between the groups that were bonded using an open-ended cylinder-shaped plastic matrix and those prepared using a closed-ended gelatin capsule matrix, nor was there a difference (P > 0.05) in the SBS when the microfilled resin restorative material was bonded to either wet or dry dentin surfaces. The use of multiple applications of Amalgambond adhesive did not markedly increase the SBS with this system. The mean bond strength of amalgam alloy (Dispersalloy) to dentin using Amalgambond Plus was 10.41 +/- 1.47 MPa. PMID- 7986445 TI - Altered tissue contribution to interfacial bond strength with acid conditioned dentin. AB - PURPOSE: To measure the shear bond strength of resin composite to dentin using three fourth generation bonding agents in combination with three different acid treatments. One such treatment was followed by sodium hypochlorite. The purpose was to determine the contribution which the collagen rich, demineralized zone made to bond strength. MATERIALS AND METHODS: Three groups, representing (1) All Bond 2/BisFil, (2) Optibond Dual Cure/XRV and (3) Scotchbond Multi-Purpose/Z100, contained four sub-groups each comprised of 10 caries-free molar teeth whose dentin was exposed in a transverse mid-coronal plane. Dressed with 320 grit, wet silicon carbide paper, the dentin surface in each sub-group was conditioned with 10% maleic acid (15 seconds), 10% phosphoric acid (20 seconds), 2.5% nitric acid (60 seconds) and 10% phosphoric acid (20 seconds) followed by 5% sodium hypochlorite (120 seconds). The bonded resin composite assemblies were stored in water at 37 degrees C for 24 hours and then subjected to shear force at a crosshead speed of 5 mm/minute until failure. RESULTS: The mean and standard deviation values derived for the groups were not statistically different from each other (P < 0.05). It was concluded that the type of conditioning agent was not a factor in achieving optimal bond strength for the system tested. Furthermore, it was tentatively concluded that the collagen-rich zone offered no direct, quantitative contribution to the interfacial bond strength which is probably derived from complete resin diffusion into the porous, partially demineralized dentin below. PMID- 7986446 TI - Dentin treatment with an oxalate solution and glass ionomer bond strength. AB - PURPOSE: To evaluate the effect of dentin surface treatment on shear bond strengths of two visible light-cured glass ionomer restorative materials to dentin. MATERIALS AND METHODS: Cylinders of Fuji II LC and VariGlass VLC were bonded to dentin surfaces that were (1) treated as directed by the manufacturer, (2) treated with a monohydrogen-monopotassium oxalate solution (Protect Dentin Desensitizer), or (3) treated with the monohydrogen-monopotassium oxalate solution followed by treatment per the manufacturer. Specimens were thermocycled and tested in shear at 7 days. Data for each restorative material were subjected to a one-way ANOVA and the Scheffe F-test (P < 0.05). After shear bond testing the specimens were examined using a stereomicroscope at x8 to determine the mode of failure (adhesive, cohesive or mixed). Dentin specimens were also surface treated as described above, sputter-coated, and examined using a scanning electron microscope. RESULTS: In every instance, the oxalate solution significantly reduced the shear bond strength of both materials. PMID- 7986447 TI - Dentin bond strength of fluoride-releasing materials. AB - PURPOSE: To evaluate the shear bond strength to dentin of fluoride-releasing materials. MATERIALS AND METHODS: Human, noncarious extracted permanent molars stored in distilled water were used. Flat buccal and lingual dentin surfaces were ground wet on 600-grit silicon carbide paper. The teeth were then distributed at random into four groups of 5 teeth (10 surfaces) each: Group 1: Fuji II LC; Group 2: Vitremer; Group 3: VariGlass; Group 4: Dyract. Cylindrical samples of the glass ionomers were prepared in plastic molds and bonded to the dentin surface according to the manufacturers' instructions. All samples were placed in distilled water for 24 hours, thermocycled for 500 cycles in distilled water at 5 degrees C and 55 degrees C and sheared with an Instron at a crosshead speed of 0.5 mm/minute. RESULTS: In MPa: Group 1: 15.96 +/- 3.28; Group 2: 9.70 +/- 2.43; Group 3: 13.48 +/- 3.35; Group 4: 21.14 +/- 5.32. ANOVA revealed that Dyract had a significantly higher bond strength than all the other products tested (P < 0.0001). Vitremer had a significantly lower bond strength. Fuji II LC had no significant difference from VariGlass. Fracture patterns, examined with the SEM, were cohesive within the cement for all groups. PMID- 7986448 TI - Factors influencing the future need for treatment of root surfaces. AB - This paper discusses the current status of root surface caries in the elderly population and the need for treatment of this condition in the future. Although root surface exposure and root caries have been reported for adults at all ages, the people at greatest risk for these conditions are the elderly. In the United States, life expectancy and the population aged 65 years and older has increased substantially, and the proportion of the elderly population who are dentate has increased and is projected to increase further. Utilization of dental services by the elderly is similar to that of employed adults. Interpretation of studies of the prevalence and incidence of root surface caries are difficult due to differences in sampling, definition of lesions, and reporting conventions. Root surface caries prevalence is related to age and continues to be a significant problem for this population as they age. Factors that may affect the future need for treatment are explored. PMID- 7986449 TI - Root caries histopathology and chemistry. AB - This paper reviews the histopathology of root surface caries, and the effect of fluoride on the root caries process. The root caries process may be defined as a dynamic equilibrium similar to enamel caries. The caries process produced acid demineralization in exposed root surfaces and resulted in a lesion body when viewed in the light microscope. A relatively intact surface layer was not always present unless root caries was observed. In the absence of fluoride, a significant surface layer was left devoid of mineral but with intact collagen. Fluoride helped to prevent lesion formation and produced radiodense banding within the lesions in in vitro models. Remineralization occurred on the remaining mineral and not on the collagen matrix devoid of mineral. The conversion of active to inactive root caries requires the formation of a mineralized layer and implies the loss of surface tissues and contour in the clinical situation. PMID- 7986450 TI - Etiology and treatment of root hypersensitivity. AB - Class V cervical lesions are often observed in older patients during their treatment planning phase, resulting from root caries, toothbrush abrasion, chemical erosion, or to absraction due to unusual tooth flexure. Besides providing a nuisance space as a food trap or plaque buildup, patients also complain of hypersensitivity to air blasts, mechanical stimulation, thermal extremes, or to osmotic fluid shifts. The location of the root lesion in relation to the cemento-enamel junction is of extreme importance. For that reason root lesions limited to the coronal portion of the tooth and completely surrounded by enamel lend themselves to traditional restorative treatment procedures. However, as the root lesion moves apically and its cavosurface circumference is increasingly bound by cementum, clinical treatment becomes much more difficult and in most cases virtually impossible with conventional retentive restorations, and they tend to threaten the root structure and the dental pulp. If these root lesions are left untreated, progressive destruction of root structure occurs and if the causative agents are not removed, the depth of the lesion will threaten the periodontium, dental pulp, and the occlusal integrity of the tooth crown. In addition, cemental lesions are often associated with increased levels of hypersensitivity. Historically, dentistry treated root lesions with direct gold, gold or porcelain inlays, amalgam alloys and crowns, all relying on resistance and retention form. When unrestorable, modification of tooth-brushing techniques along with desensitizing agents were the only desirable treatment due to problems involved with the insertion of a proper restoration. Clinical studies have reported these procedures are often transient, offering no durable restoration of the tooth or elimination of the hypersensitivity.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7986451 TI - Fluoride, remineralization and root caries. AB - This paper reviews the probable mechanism of dental caries and the role of fluoride in the inhibition or reversal of that process. The initial stages of root caries are comparable to enamel caries, being the acid dissolution of mineral resulting from acids generated by bacterial metabolism. The fermentation of carbohydrates by oral bacteria including mutans streptococci and lactobacilli initiate the root caries process, removing mineral from among the organic matrix which is primarily composed of collagen. Subsequent to this demineralization, the organic material can be further broken down by bacterial enzymes. Fluoride inhibits mineral loss during the acid dissolution process and enhances remineralization in a similar manner to that which occurs in dental enamel. PMID- 7986452 TI - Enamel and dentin demineralization inhibition of fluoride-releasing materials. AB - Fluoride-releasing dental restorative materials may provide an additional benefit in preventive dentistry. Although not currently available in the United States, a fluoride-releasing amalgam has demonstrated recurrent caries inhibition at enamel and dentin restoration margins. Likewise, both chemical-cured and light-cured glass ionomer cements have demonstrated caries inhibition at enamel and dentin restoration margins. Fluoride-releasing resin composites have also consistently demonstrated recurrent caries inhibition at enamel margins, yet there are conflicting results whether caries inhibition occurs at dentin margins. Preliminary studies indicate that glass ionomer cement and fluoride-releasing resin composite have synergistic effects with fluoride rinses and fluoridated dentifrices, in the remineralization of incipient enamel caries. The materials may act as a fluoride delivery system. Upon exposure to additional external fluoride, the material surface undergoes an increase in fluoride. This fluoride is subsequently released and has demonstrated demineralization inhibition and even remineralization at adjacent tooth structure. Clinical research to evaluate these fluoride-releasing restorative materials may provide further information for clinical recommendations. PMID- 7986453 TI - Root surface treatment with glass ionomers and resin composites. AB - Recommendations for restorative treatments of root surfaces are made difficult by a lack of information on the etiology of root conditions and on the clinical performance of available materials used to treat these conditions. Resin composite and glass ionomer materials are popular restorative materials because they are esthetic and can bond to tooth structure. However, the role each can play in restoration of root surface lesions is not well documented. This article presents a rationale for using these materials for a number of restorative situations. PMID- 7986454 TI - Glass ionomer cements and future research. AB - Once a root surface lesion has extended into tooth structure beyond the point at which it can be successfully remineralized it is necessary to carry out traditional restorative procedures. Often the extent of the lesion is difficult to define and development of a pulp exposure is an ever present risk. Access may be difficult and placement of a restorative material, such as amalgam, which requires positive condensation for correct placement, poses a problem. The principal requirement of a restoration in such a lesion is that it should completely seal the restoration/tooth interface and prevent the ingress of further bacteria or bacterial nutrients. As there will be no occlusal load, physical properties of the restorative material are not significant. As these lesions will often occur on anterior teeth it is desirable that the material be reasonably esthetic although there will be no need for a great depth of translucency. The modern trend to light curing of restorative materials facilitates placement but there are situations with these lesions where it is difficult or impossible to obtain proper access for the light and an auto cure material may be indicated. Because the patient who presents with root surface lesions is likely to pose a continuing problem, it is desirable that the restorative material have some degree of in-built protection against further demineralization. An ongoing fluoride release is very desirable. Glass ionomer cement fulfils all the above requirements and is therefore at present the material of choice. Either the original auto cure cement or the newer dual cure materials will provide a complete marginal seal with a continuing fluoride release throughout the life of the restoration and both varieties are sufficiently esthetic to be entirely acceptable. PMID- 7986455 TI - Evaluation and treatment of bacterial microleakage. AB - Recent data have shown a correlation between pulp response and material biocompatibility when microleakage is prevented. Considering vital dentin, the dentist must keep in mind that it is an extension of the pulp, presenting the first line of response to the consequences of microleakage. Healing of the dental pulp is ensured when a clinical seal is provided to prevent bacterial microleakage. Microleakage is a biological phenomenon with several important clinical implications. The affective component clinically presents as dentin postoperative hypersensitivity due to the episodic hydrodynamic fluid movement within the tubule complex. The effective component is the disease process which signals the dentin and pulp complex to respond by deposition of sclerotic and reparative dentin deposition. Uncontrolled microleakage generally produces patient pain as well as to later allow bacterial infection resulting in recurrent caries and pulp inflammation. The dynamic, permeable nature of the dentin interface allows residual bacteria to proliferate following cavity preparation. Following sterile operative procedures, bacteria have been shown to percolate into the cavosurface margin resulting in recurrent caries and pulp inflammation. This report considers biological data emphasizing the clinical necessity to provide a hermetic seal to prepared dentin to prevent both dentin hypersensitivity and pulp inflammation. PMID- 7986456 TI - Exposed Root Interactions Symposium: consensus and recommendations. PMID- 7986457 TI - Plasma renin predicts success of antihypertensive drug withdrawal. AB - This study examined the relationship of plasma renin activity (PRA) to the likelihood of maintaining blood pressure control after discontinuation of antihypertensive medication. Patients whose blood pressure was previously treated and controlled in the Hypertension Detection and Follow-up Program were enrolled in the Dietary Intervention Study of Hypertension. After stratification by obesity, patients were randomized to discontinue medication with no dietary intervention, sodium restriction, or weight reduction for the obese. Among 496 subjects in the Dietary Intervention Study of Hypertension, 75 were randomly selected for PRA measurement at 4 months after intervention, and all had their blood pressure under control at that time. Patients were followed up for 56 weeks after randomization. The endpoint was return to antihypertensive medication due to elevated diastolic blood pressure. Kaplan-Meier survival analysis showed that subjects with PRA < or = 53.3 ng/100 mL/h, the median level, had a lower cumulative success rate for remaining off antihypertensive drug than those with PRA above the median (P = .046). In Cox regression analysis controlling for 24-h urinary sodium level, baseline diastolic blood pressure, age, sex, race, obesity, and dietary intervention group, a unit decrease in log PRA was associated with a 2.78-fold increase in risk of returning to drug (P = .006); this inverse relationship was independent of dietary intervention and change in diastolic blood pressure in the first 4 months before PRA was measured. The data indicate that patients with low PRA are less likely to maintain blood pressure control without drugs than patients with high PRA. PMID- 7986458 TI - Life style as a determinant of blood pressure in the general population. AB - This study investigated which life style factors were correlated with the level and the variability of systolic (SBP) and diastolic (DBP) pressure in a random population sample. Ten blood pressure readings were obtained at home in 405 men and 379 women (20 to 84 years). Each person's average pressure level was computed together with the standard deviation as index of variability. Sodium, potassium, and alcohol intake, smoking habits, social class, psychoemotional stress, and the calories spent at work and in sports were assessed from a questionnaire and from determinations on serum and on a 24-h urine sample. A P10 to P90 (10th and 90th percentile) increase of alcohol intake, as reflected by serum gamma glutamyltransferase, was associated with a 3.2 +/- 0.9 mm Hg higher DBP in men and with a 3.1 +/- 1.6 mm Hg higher SBP and a 1.5 +/- 0.8 mm Hg higher DBP in women. A P10 to P90 increase in the calories spent in sports was accompanied by a decrease in pressure, averaging 1.5 +/- 0.8 mm Hg for DBP in men and 2.4 +/- 1.2 mm Hg and 1.8 +/- 0.8 mm Hg for SBP and DBP in women. A 2.2 +/- 0.7 mm Hg higher DBP was observed in women living in a working class area. After adjustment for age, the variability of DBP was inversely correlated with self-rated physical activity in men, whereas women living in a working class area showed a decreased SBP variability. In conclusion, in an affluent Western population, alcohol intake, participation in sports, and living in a working class area were identified as the life style factors of importance for the blood pressure level. By contrast, blood pressure variability, as measured in the present study, was only to a minor extent influenced by life style. PMID- 7986459 TI - Effects of exercise and therapy on ventricular emptying and filling in mildly hypertensive patients. AB - Left ventricular (LV) filling was studied in 18 healthy subjects and 19 mildly hypertensive patients before and after 50% and 70% of maximal supine exercise using radionuclide ventriculography. In addition, in the hypertensive patients, the effects of oral verapamil and lisinopril treatment on LV filling before and after exercise were studied. At rest, hypertensive patients compared with healthy subjects had a lower peak filling rate, ratio of peak filling to peak emptying rate, first-half filling fraction, and a longer isovolumic duration. With exercise, LV filling measures were not different between healthy subjects and hypertensive patients. In the hypertensive patients at rest, compared with before treatment, lisinopril prolonged isovolumic duration and verapamil had no effect on LV filling; at 50% maximal exercise compared with before treatment, verapamil shortened the time to peak filling rate and isovolumic duration and increased first-half filling fraction but, at 70% maximal exercise, verapamil had no effect, whereas lisinopril did not alter exercise LV filling at either exercise level. Thus, the early abnormal LV filling in mildly hypertensive patients is influenced by therapeutic interventions both at rest and with exercise. PMID- 7986460 TI - Quality-adjusted meta-analysis of the hypertension/coronary dilemma. AB - Primary investigators of randomized drug trials in hypertension were invited to rate quality of such trials. The intention of the survey was to ask if antihypertensive drug therapy reduces incidence of coronary heart disease (CHD) in hypertensive patients. Response was obtained for 7 of the 11 invited investigators, covering 69% of patients and 75% of CHD cases. Principal component analysis was used to construct a quality score based on answers to 12 questions along visual analog scales. The score correlated well with the answer to a global question of overall quality given by the raters. No systematic tendency toward favoring one's own trial could be demonstrated, therefore, all raters have contributed to the rating. The trials with the highest rated quality to answer the research question were Systolic Hypertension in the Elderly Program (SHEP), Australian National Blood Pressure Study, Medical Research Council, Veterans Administration, and European Working Party of Hypertension in the Elderly. The large Heart Detection and Follow-up Program (HDFP) trial was rated at 11th place among the trials with a score of < 40% of the SHEP. The small trials performed in the 1960s were placed at the bottom of the ranking list. Because SHEP is the only trial without diastolic hypertension, results were given with and without SHEP results. When incorporating the quality score into a meta-analysis of CHD outcome, results were dependent on whether SHEP was included or not. For diastolic hypertension only, the effect of therapy was estimated to be about 8% for all higher quality studies, whereas inclusion of the lower quality HDFP changed it to 14%. When isolated systolic hypertension trial was pooled with the others, no major relation to quality rating was observed. A 14% CHD preventive efficacy was established when pooling the three top quality studies. This stayed unchanged until HDFP at rank 11 was included raising this estimate to 16%. Inclusion of the two latest published trials in the elderly, the Medical Research Council trial of treatment of hypertension in older adults and the Swedish Trial in Old Patients with hypertension, did not change this overall estimate of 16% (standard error = 3.8%). It is concluded that if all randomized drug trials in hypertension had the same treatment efficacy, the estimated CHD prevention would be in the range of 15%. Subgroup analyses revealed no relationship to age, but a difference in efficacy was shown depending on whether the trials were performed in the United States or elsewhere. Also, patients at higher risk levels showed better benefit than lower risk patients. PMID- 7986461 TI - Deficient activity of stimulatory nucleotide-binding regulatory protein in lymphocytes from patients with essential hypertension. AB - Lymphocytes are widely used as a model for the cardiovascular beta-adrenoceptor adenylate cyclase system. We evaluated the role of this system in the pathogenesis of hypertension by studying lymphocytes obtained from patients with essential hypertension. Untreated hypertensive patients and normotensive control subjects were studied. The number and affinity of the beta-adrenoceptors were measured by a radioligand binding method with 125I-cyanopindolol. The responses of cyclic adenosine monophosphate (cAMP) to isoproterenol, cholera toxin, and forskolin were also determined. The concentration and affinity of beta adrenoceptors did not differ significantly in the two groups, nor was a significant difference found in the basal level of cAMP. The effects of isoproterenol on the accumulation of cAMP were reduced in the lymphocytes from the hypertensive compared with the normotensive subjects. There was no significant difference in the effect of forskolin on cAMP accumulation in the two groups. These results indicate that the activity of the stimulatory nucleotide binding regulatory protein (Gs-protein) is reduced in lymphocytes from patients with essential hypertension. This defect of Gs-protein in the lymphocytes may represent a defect of Gs-protein in the cardiovascular system in such patients. PMID- 7986462 TI - Elevated immunoreactive endothelin levels in patients with pheochromocytoma. AB - Plasma immunoreactive endothelin-1 (ET-1) concentrations were measured in 44 patients with pheochromocytoma, 31 patients with essential hypertension, and 20 healthy control subjects. Plasma ET-1 concentrations in patients with pheochromocytoma were 18.2 +/- 3.2 fmol/mL (mean +/- SEM), which was significantly higher than those of essential hypertension and healthy control subjects (7.3 +/- 0.4, 7.1 +/- 0.4 fmol/mL, respectively, P < .01). Plasma ET-1 concentrations in patients with essential hypertension and control subjects were similar. In patients with pheochromocytoma, hypertensive group had higher ET-1 than normotensive group (23.0 +/- 5.5 v 12.4 +/- 2.2 fmol/mL), but the difference was not significant. In 17 patients with pheochromocytoma, the elevated plasma ET 1 concentrations (17.4 +/- 4.7 fmol/mL) returned to normal levels (7.9 +/- 0.6 fmol/mL, P < .05) after surgical resection of the tumor. ET-1 contents in the 26 tumor tissues (1.40 +/- 0.29 pmol/g) were higher than those in 7 normal adrenal medullas (0.44 +/- 0.12 pmol/g). Systolic, diastolic, and mean blood pressures were better correlated with plasma norepinephrine than ET-1 in patients with pheochromocytoma. These data indicate that pheochromocytoma might produce and secrete excessive amounts of ET-1. The hypertension in patients with pheochromocytoma is mainly catecholamine-dependent, but may be secondarily ET-1 dependent. PMID- 7986463 TI - Diurnal variation in prorenin in relation to other humoral factors and hemodynamics. AB - Diurnal variation has been demonstrated for blood pressure and heart function. Several hormones influence these hemodynamic parameters. This study investigates the diurnal variation in plasma prorenin in relation to renin, atrial natriuretic peptide (ANP), norepinephrine, and hemodynamic changes. Circulating plasma prorenin may be able to serve as a marker for the activity of the local renin angiotensin system. In 12 healthy male volunteers who were allowed to carry out quiet activity, hemodynamic factors and the plasma levels of hormones were monitored at 2-h intervals for 26 h. Blood pressure was measured every hour. In accordance with the literature, during the night blood pressure (4%), cardiac index (19%), stroke index (10%), and heart rate (10%) decreased in a classic day night pattern. Systemic vascular resistance increased during the night (23%). No classic day-night pattern was found for ANP, although it increased (15%) at night and showed a peak early in the night. This peak seemed to be influenced by posture. A classic day-night pattern was demonstrated for norepinephrine and prorenin. Norepinephrine was lower (18%) at night and increased as soon as the subjects awoke, while they were still in bed. Therefore, plasma norepinephrine levels seemed to be related to awakening. Plasma prorenin decreased at night (6%). Renin fluctuated throughout the day, but showed no clear day-night pattern. In conclusion, renin fluctuated throughout the day and did not show a classic day night pattern. In contrast, prorenin fluctuated less and showed 6% higher levels during the day compared to the night. The origin and clinical significance of this small diurnal variation in prorenin is not clear yet. PMID- 7986464 TI - Comparison of the effects of captopril and nicardipine on insulin sensitivity and thrombotic profile in patients with hypertension and android obesity. CaptISM Study Group. Captopril Insulin Sensitivity Multicenter Study Group. AB - Hypertension is often related to metabolic disorders, such as android obesity, glucose intolerance, dyslipidemia, and hyperinsulinism (X syndrome). Insulin resistance (IR), described as the common link among these disorders, could contribute to an increase in coronary risk. The euglycemic insulin clamp technique has been used to show that different classes of antihypertensive agents have different effects on IR. The purpose of this multicenter study was to compare the effects of captopril to those of nicardipine on insulin profile using the oral glucose tolerance test (OGTT), a routine-feasible test. After a 1-month single-blind placebo period, 154 patients with hypertension and android obesity were randomized to 3 months of double-blind therapy with either 50 mg captopril twice daily (n = 77) or 50 mg nicardipine twice daily n = 77). An OGTT with an assay of insulin was performed before and after active treatment. Lipid parameters, Factor VII (F VII), fibrinogen, plasminogen activator inhibitor 1 (PAI-1), and insulin-like growth factor I (IGF-I) were measured at the same time. After 3 months of treatment, the changes from baseline in mean +/- SD values for the insulin area under the curve (AUC) were -24.8 +/- 107.4 microIU x h/mL ( 15.2%) for captopril v 6.1 +/- 98.6 microIU x h/mL (4.8%) for nicardipine (P = .072). Changes in peak insulin values were -18.3 +/- 86.2 microIU/mL (-14%) for captopril v 6.7 +/- 79.4 microIU/mL (6.6%) for nicardipine (P = .070).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7986465 TI - Glucose tolerance and blood pressure are improved in the spontaneously hypertensive rat by ethyl-2-(6-(4-chlorophenoxy)-hexyl)oxirane-2-carboxylate (etomoxir), an inhibitor of fatty acid oxidation. AB - We have demonstrated that glucose tolerance and insulin action are impaired in the spontaneously hypertensive rat (SHR), and that free fatty acids are elevated. Etomoxir, an inhibitor of fatty acid oxidation, has been shown to improve hyperglycemia in diabetic rats. We therefore performed oral glucose tolerance tests in SHR to assess glucose tolerance and insulin action in response to etomoxir. Because of the proposed relation between insulin action and hypertension, we examined the effect of etomoxir on blood pressure. Thirteen-week old male SHR were randomized into two groups. Food was withdrawn at 8 AM and at 11 AM, animals received etomoxir (50 mg/kg) or control vehicle by gavage. Oral glucose tolerance tests were started at 1 PM. In other studies, 21-week-old male SHR were randomized into two groups. Animals were treated by gavage with etomoxir (50 mg/kg) or control vehicle, and blood pressure was measured noninvasively before and after treatment. Two weeks later, these experiments were repeated, but the treatments were reversed. In etomoxir-treated rats, the glucose response was significantly lower, whereas the insulin response was not significantly different. The combination of lowered glucose response, in the face of an unchanged insulin response, suggests an improvement in insulin action. However, fasting free fatty acids were higher, as was the free fatty acid response following etomoxir treatment. There was a dramatic decrease in blood pressure following etomoxir, with significant differences at 1.25, 3, 4.5, and 21 h after dosing. In summary, etomoxir treatment improved glucose tolerance and insulin action in SHR, whereas free fatty acid values were higher.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7986466 TI - Ischemic dysfunction and impaired recovery in hypertensive hypertrophied hearts is associated with exaggerated intracellular sodium accumulation. AB - The primary objectives of this study were to determine if hypertrophied spontaneously hypertensive rat (SHR) hearts exhibited a greater increase in intracellular sodium (Na+i) compared with Wistar-Kyoto (WKY) control rats during low flow ischemia, and to determine whether Na+i accumulation in these hearts was associated with greater ischemic dysfunction and damage. In addition, intracellular pH and high energy phosphates were monitored to assess the relationships between changes in these variables and changes in Na+i. Interleaved 31P and 23Na spectra were acquired in perfused hearts from 8- to 10-month-old rats during low flow ischemia and reperfusion, while left ventricular pressures were monitored continuously. The majority of SHR (n = 13) exhibited an increase in Na+ similar to that for WKY and did not demonstrate exaggerated ischemic dysfunction or damage. However, a subgroup of SHR (n = 7) exhibited exaggerated Na+i accumulation during ischemia, compared with WKY, that was associated with contractile failure and a greater increase in left ventricular end diastolic pressure during ischemia, and slower recovery of developed pressure during reperfusion. Greater Na+i accumulation in this SHR subgroup preceded significantly greater depletion of high energy phosphates compared with WKY. In conclusion, increased Na+i accumulation was observed in all hypertrophied hearts with greater ischemic dysfunction compared with WKY. These results suggest that impaired Na+i handling may indeed contribute to the greater susceptibility of hypertrophied hearts to ischemic dysfunction and damage. PMID- 7986467 TI - Prolonged increase in blood pressure by a single oral dose of caffeine in mildly hypertensive men. AB - Caffeine is known to raise blood pressure (BP). We examined a single oral dose of caffeine (3.3 mg/kg, equivalent to 2 to 3 cups of coffee) on BP in 18 hypertensive (HTN) and 12 age-matched, normotensive (NT) men for 3 h. Systolic BPs were significantly higher after caffeine for both groups (P < .001) for the entire 3 h. The HTN group showed persistent elevation in diastolic BP for 3 h, whereas the increment of diastolic BP became smaller in the NT group 90 min after caffeine ingestion. Our results suggest that caffeine consumption may affect both diagnosis and treatment of hypertension and abstinence from caffeine may be beneficial, especially for hypertensive individuals. PMID- 7986468 TI - Frequency of a deletion polymorphism in the gene for angiotensin converting enzyme is increased in African-Americans with hypertension. AB - In white populations, a deletion polymorphism in the gene for angiotensin converting enzyme (ACE) appears to be associated with increased risk for myocardial infarction but not for hypertension. In a population-association study in African-Americans, we compared the frequency of the ACE deletion polymorphism in subjects with hypertension versus those with normal blood pressure. The frequency of the ACE deletion allele was greater in African-Americans with hypertension than in those with normal blood pressure (P < 0.05). These findings raise the possibility that in some patient subgroups, sequence variation in or near the ACE gene may contribute to the risk for hypertension. PMID- 7986469 TI - Unchanged neurogenic vasoconstrictor response after exercise during angiotensin converting enzyme inhibition with fosinopril. AB - In a double-blind, randomized, cross-over, placebo- and rest-period controlled study with two 4-week treatment periods, we examined the effects of angiotensin converting enzyme (ACE) inhibition with fosinopril (20 mg/day) on the postexercise pressor and forearm vasoconstrictor responses to a 60 sec cold pressor test. The results indicate that pressor and vasoconstrictor responses were unaffected by prior exercise, fosinopril, and both interventions combined. Expression of the responses as percent change from baseline levels provided identical results indicating that changes in baseline values did not mask an altered vascular responsiveness. It is concluded that skeletal muscle vascular responsiveness to sympathetic nervous activity is unchanged after exercise or during ACE inhibition with fosinopril. PMID- 7986470 TI - Angiotensin II potentiates the arterial pressure response to volume loading in humans. AB - Angiotensin II (AII) has many potential effects on blood pressure regulation in addition to direct vasoconstriction. This study tested the hypothesis that minimally pressor infusions of AII, which themselves exert minimal effects on blood pressure, might significantly perturb the pressure response to hypertonic volume expansion in healthy humans. Accordingly, 3% saline was infused at 0.1 mL/kg/min in 13 healthy volunteers, both with and without concomitant AII infusion (2 ng/kg/min) on separate days. On a third day, AII was infused alone for 2 h in eight of these subjects. Eight subjects also were studied with 3% saline plus concomitant phenylephrine infusion as a "positive control." AII and phenylephrine exerted similar, small effects on mean arterial pressure (3.3 +/- 1.5 v 3.0 +/- 1.0 mm Hg, P = NS) before the infusion of AII. When 3% saline was infused alone, mean arterial pressure did not rise significantly. In the presence of AII, mean arterial pressure rose from 89 +/- 10 to 97 +/- 11 mm Hg (P < .01 v control; P < .05 v 3% saline alone). In the presence of phenylephrine, the mean arterial pressure did not increase during 3% saline infusion, similar to the results during 3% saline infusion alone. Plasma osmolality and arginine vasopressin levels were not different during 3% saline infusions with and without AII or with phenylephrine. Thus, a minimally pressor infusion of AII significantly potentiated the response of mean arterial pressure to hypertonic volume expansion in healthy humans.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7986471 TI - Resistance to metabolic actions of insulin and its role in hypertension. AB - Insulin resistance and hyperinsulinemia have been postulated to be important in raising blood pressure in obese as well as lean hypertensive individuals. However, cause-and-effect relationships among these variables have not been clearly established. The three most widely used methods to assess insulin resistance in vivo (fasting plasma insulin, glucose disposal after a glucose load, or glucose disposal during a hyperinsulinemic euglycemic clamp) may provide different estimates of insulin resistance under various physiological and pathophysiological conditions. Fasting hyperinsulinemia may reflect mainly hepatic insulin resistance, whereas impairment of glucose disposal indicates resistance to the metabolic effects of insulin in skeletal muscle. The importance of these different sites of insulin resistance in the etiology of cardiovascular diseases, however, is still unclear. Although hyperinsulinemia and insulin resistance have been speculated to cause hypertension, most of the evidence supporting this hypothesis has come either from correlation studies or from short term studies of the cardiovascular, renal, and sympathetic effects of insulin. The few long-term studies that have been conducted in dogs and in humans do not support the insulin concept of hypertension. In fact, these studies suggest that the vasodilator actions of insulin tend to reduce, rather than elevate, blood pressure. Correlations between insulin resistance, hyperinsulinemia, and hypertension do not appear to be explainable by the concept that insulin resistance occurs secondary to hypertension. Obesity may be a key factor in explaining these relationships; weight gain appears to cause insulin resistance, compensatory hyperinsulinemia, and hypertension through parallel, but not necessarily linked, mechanisms. However, insulin resistance and compensatory hyperinsulinemia may contribute to increased risk of other cardiovascular diseases associated with hypertension, such as coronary artery disease. PMID- 7986472 TI - Use of drugs in patients with renal insufficiency. Workshop report. AB - Summary of a workshop on drug dosing in renal insufficiency is presented. Neural networks, computer-assisted dosing, and other methods of efficacious and safe dosing in renal failure are emphasized. PMID- 7986473 TI - Outcome measurement in kidney disease. AB - The effects of chronic kidney disease have been difficult to quantify using traditional measures of mortality and biological processes. New approaches to the quantification of outcomes in kidney disease are required. A wide variety of methods have become available and are now in use in some studies. Psychometric approaches, such as the Sickness Impact Profile and the Kidney Disease Questionnaire, have been shown to be responsive to change in some clinical studies. In order to estimate the cost-effectiveness of investments in kidney disease, decision theory approaches are required. We argue that these decision theory approaches should be given serious consideration for inclusion in clinical trials and in the US Renal Data System. PMID- 7986474 TI - T cell function in chronic renal failure and dialysis. AB - This article briefly summarizes the literature regarding possible defects in cell mediated immunity in the setting of chronic renal failure. It is difficult to precisely determine the proximate cause or level of such defects from most studies. Confounding variables include reports on mixed patient populations (predialytic chronic renal failure, hemodialysis patients, and peritoneal dialysis patients) and studies before and after the introduction of erythropoietin for end-stage renal disease patients. While it seems clear that lymphopenia, suboptimal responses to mitogens, abnormal cytokine gene expression, and abnormal IL-2R expression are seen in a number of dialysis patients, the role of uremia versus dialysis in producing these abnormalities is unclear. In addition, it is difficult to determine whether T cell abnormalities are primary or secondary to impaired function of other interacting immune cells, such as macrophages. Clinical implications of defects in cell-mediated immunity are additionally discussed. PMID- 7986475 TI - Quantitation of dialysis. The importance of membrane and middle molecules. AB - Despite the availability of calcitriol and recombinant erythropoietin to replace two major endocrine functions of the kidneys, mortality in chronic hemodialysis patients remains substantially higher than that in the general population. This suggests that most, if not all, patients are underdialyzed. While increasing small solute clearance by dialysis using urea kinetics as a guide improves clinical outcome, 'adequate' treatment using current techniques is only an arbitrary definition, since solute removal by dialysis remains far inferior to that of the normal native kidneys. In recent years, significant advances have been made in the structural and functional characterization of toxic uremic solutes that are in the higher molecular size range ('middle molecules'). Several lines of evidence suggest that, in addition to small solutes, removal of middle molecules is also advantageous. The potential beneficial effects of synthetic high flux hemodialysis membranes are probably attributed to both their solute clearance profiles as well as their biocompatibility characteristics. PMID- 7986476 TI - Serum advanced glycosylation end products: a new class of uremic toxins? AB - Irreversible advanced glycosylation end products (AGE) are shown to induce tissue damage by a variety of chemical and cellular mechanisms. When administered to normal animals, AGE-modified albumin reacts covalently with tissue proteins to produce complex vascular alterations closely resembling diabetic vasculopathy. In humans, the clearance of serum with renal insufficiency and is severely impaired in diabetic patients with end-stage renal disease (ESRD). The renal clearance of AGE-peptides was estimated at 0.72 +/- 0.23 ml/min for normal subjects, and 0.61 +/- 0.2 ml/min for diabetics with normal glomerular filtration rate (GFR) (p value NS). After comparing different modes of treatment of patients with ESRD, we noted that, although conventional hemodialysis is ineffective, high-flux dialysis (HF) markedly reduces AGE levels only to return to near-pretreatment levels within 3 h. In chronic ambulatory peritoneal dialysis (CAPD)-treated patients, serum AGE are similar to those achieved by hemodialysis. In contrast, AGE levels in diabetics with renal transplantation decreased 8 h after surgery and remained within the normal range over the long term. Human serum AGE peptides (M.W. between 2,000 and 6,000) are shown to retain strong cross-linking activity with collagen in vitro. AGE peptides in human circulation may represent a thus far unrecognized class of reactive and potentially toxic substances which can exacerbate extrarenal vascular pathology, through their covalent attachment onto matrix proteins. PMID- 7986477 TI - Erythropoietin overview--1993. AB - Knowledge continues to grow on the biology of endogenous erythropoietin (EPO), its effects on red blood cell physiology, and the use of the recombinant form of the hormone. In addition to oxygen delivery, oxygen consumption may be important in stimulating EPO production. This production is likely mediated by an intracellular messenger system other than cAMP. Once released, EPO prevents programmed cell death of BFU-E and CFU-E cells. Recent evidence suggests that lack of EPO, rather than the presence of EPO inhibitors, is the cause of the anemia seen in renal patients. Recombinant EPO has been available clinically since mid 1989. Nearly two thirds of dialysis patients are receiving this agent, although low doses are the rule, with the average hematocrit achieved of only 31%. EPO dosing has been subjected to kinetic modeling that has revealed a wide range in RBC half-life from patient to patient. This accounts in part for the varying maintenance dosing requirements. An additional modulating factor in the response to EPO is severe, secondary hyperparathyroidism with bone marrow fibrosis which may be reversible with medical or surgical parathyroidectomy. Hypertension continues to occur in 20-35% of patients given EPO. This effect may be mediated by endothelin which appears to be stimulated by EPO administration. Treatment of the anemia of renal failure leads to many organ system benefits including improved muscle metabolism, decreased left ventricular hypertrophy, enhanced immune responses to hepatitis vaccine, and improved brain electrophysiology. he optimal target hematocrit to achieve the greatest benefits for the patient at an acceptable cost remains to be determined. PMID- 7986478 TI - Hyperlipidemia of chronic renal failure. AB - Plasma triglycerides are increased in the majority of patients with advanced renal failure but cholesterol is not. HDL cholesterol is reduced while LDL IDL and VLDL cholesterol is increased. Lecithin:cholesterol acyltransferase (LCAT), an enzyme necessary for HDL maturation, is reduced in chronic renal failure (CRF). As a consequence, while all subtypes of HDL are reduced, the small HDL3 subtype is relatively enriched at the expense of the larger, more functional HDL2 subtype. Triglycerides are increased in all lipoprotein fractions. HDL-associated apolipoproteins, apo A-I and A-II are decreased, while apo B is increased. Lipoprotein catabolic rate is reduced, but the cause of hyperlipidemia is multifactorial; reduced lipoprotein lipase (LPL) activity, increased concentration of apo C-III (a specific inhibitor of LPL) in plasma, secondary hyperparathyroidism, insulin resistance. Hyperlipidemia is not corrected by dialysis. Lipid levels are somewhat higher in CAPD patients, possibly as a consequence of increased glucose absorption or as a consequence of transperitoneal HDL losses. Triglycerides decrease and cholesterol increases following transplantation. Oxidized lipids are increased in plasma of patients with CRF. Plasma polyunsaturated fatty acids are decreased and saturated fatty acids increased. The same changes occur in the lipid bilayers composing leukocytes and red blood cell membranes. These changes result in altered membrane fluidity, and are corrected by dialysis. While atherosclerotic disease is a leading cause of death in dialysis patients, it is not certain that the specific lipid disorders of CRF are responsible for this morbidity, nor is it recommended at this time that qualitative abnormalities be treated pharmacologically in the absence of increased lipid levels. PMID- 7986479 TI - Nutritional assessment. AB - Measurements of body composition are made to assess nutritional status. The measurements used for these studies should be selected on the basis of reliability, as well as simplicity and costs, and reliability depends on the information required. In normal adults simple estimates of fat and lean tissue (LBM), i.e. the anthropometric measurements of weight, height and skin fold thickness, should be sufficient since the proportions, in LBM, of water, protein and bone mineral are relatively constant. Measurements of body water (by isotope dilution or bioelectrical impedance) allow indirect estimates of fat and LBM that are reliable, provided that water is a constant proportion of LBM. In disease states, however, including renal disease, it is well established that the proportion of water in LBM varies from significant water overload to dehydration. In disease, it is important to determine not only total LBM but also the quality of LBM, determining essential body protein as well as body water. Body protein can be measured directly by nuclear techniques. This procedure should be more readily available for the clinical investigation of nutritional status. PMID- 7986480 TI - Biomaterials for hemodialysis access. AB - While the optimal vascular conduit for hemodialysis is undeniably an arterialized autogenous subcutaneous vein, only a minority of end-stage renal disease patients can count on such access: the remainder require implantation of a biomaterial conduit. This paper will briefly survey current biografts used for hemodialysis access, with an emphasis on their known limitations, and will delineate the questions to be asked--and answered--in the development of optimal dialysis access grafts. PMID- 7986481 TI - Noninvasive cardiac testing in the end-stage renal disease patient. AB - Renal transplant candidates are at increased risk for future cardiac death- approximately 5-10% per year. Invasive testing by coronary angiography has been used to assess the cardiac risk. However this is expensive and carries its own risks to residual renal function as well as cardiac morbidity and mortality. Screening of patients by clinical risk factors may obviate the need for invasive or noninvasive testing in a significant number (approximately 50%) of the renal transplant candidates. Further noninvasive testing with exercise or dipyridamole thallium-201 stress testing in the high-risk patients may be a more cost effective screening test than coronary angiography. Other noninvasive testing modalities may also prove useful in the future but have not yet been proven in this unique patient population. The characterization of a renal transplant candidate's cardiac risk may assist the clinicians in prioritizing the candidate for transplantation. Recent evidence also suggests that revascularization of the diabetic renal transplant candidate with significant coronary artery disease (which is approachable by angioplasty or bypass surgery) may modify their cardiac risk. Randomized studies of the efficacy of revascularization or medical therapy interventions in the nondiabetic renal transplant candidate with coronary artery disease have not been performed. PMID- 7986482 TI - [Evaluation of an increased blood level of GGT, CDT, methanol, acetone and isopropanol in alcohol intoxicated automobile drivers. Alcoholism indicators instead of medical-psychological examination]. AB - Several thousand blood samples were taken from alcoholized drivers at the Blood Alcohol Examination Centre of the Institute of legal Medicine at Cologne University. These samples showed blood alcohol contents (BAC) as well as GGT, CDT, methanol, acetone and isopropanol levels which indicated alcohol addiction. The blood samples were selected by the drivers' ages and their BAC, but in some cases the GGT also played a role. In the majority of cases 1 or 2 parameters were measured. In 200 cases all four indicators were determined. The four parameters characterize a different problematic drinking behaviour. GGT characterizes chronic, long-term misuse, CDT characterizes occasional misuse, methanol characterizes current addicted drinking and acetone and isopropanol characterize metabolic disorders caused by alcohol. The importance of parameters is thoroughly discussed, also in relation to incorrectly measured positive values and the relation between alcohol consumption and -problems. Methanol values above 10 mg/kg, GGT activities above 100 U/l and CDT levels above 60 U/l provide sufficient proof of there being an alcohol problem which requires treatment. The levels of other indicators need not be above normal to determine this. The proportion of drivers under the influence of alcohol with problematic alcohol levels increases significantly when the BAC is above 2.0 per mille. However, there have been drivers with alcohol problems with lower BAC levels. DUI offenders addicted to alcohol are quite frequently over 40 years old. A correlation between the single indicators and the BAC is rarely found. If a correlation is to be found, it would be most likely with drivers whose BAC lies above 2.0 per mille. The mentioned indicators would detect an alcohol problem from the blood sample taken for the blood alcohol test. Alcohol problems may be detected and treated shortly after the DUI offence. This method is comparatively cheaper than medical-psychological-examinations as well as being based on objective and verifiable parameters. PMID- 7986483 TI - [Checking the identity of stored blood samples]. AB - The Institute for Legal Medicine in Hamburg carried out a retrospective analysis for identity checks of stored blood samples. A total of 70,597 blood alcohol examinations were carried out between 1984 and 1993. Identity checks were commissioned for 187 people (0.26% of the total of all blood samples). Amongst those, 33 cases of "non-identity" were established (17.6% of all checked blood samples). The results are compared to an earlier study by Kleiber over a span of 10 years--between 1974 and 1983. While the frequency of identity checks decreased, the cases of "non-identity" increased quite drastically in comparison. In the cases where "non-identity" could be detected, it was not a matter of blood samples getting mixed up. However, it was a matter of intentional, sometimes very cunning ploys by means of other people's IDs, forged IDs and impersonations. In these cases the later checking of the blood group systems proved to be important evidence in the criminal proceedings. This evidence would not be available if there were to be no blood alcohol tests. PMID- 7986484 TI - Neuroimmune mechanisms in Alzheimer disease pathogenesis. AB - Lesions in Alzheimer disease are characterized by the assembly of a variety of cells and proteins associated with the immune system. Activated microglia express high levels of major histocompatibility complex glycoproteins and receptors for complement. Small numbers of T lymphocytes infiltrate tissue. Proteins of the classical complement pathway are closely connected with beta-amyloid deposits. beta-Amyloid protein binds C1q in vitro and activates the pathway. The membrane attack complex of complement, as well as proteins that defend against that complex, colocalize with dystrophic neurites. These data imply that an autodestructive process is occurring in Alzheimer disease, that overactive microglia might be responsible, and that antiinflammatory drugs might be an effective form of therapy. PMID- 7986485 TI - New opportunities in AD research--roles of immunoinflammatory responses and glia. PMID- 7986486 TI - Primary caregivers' descriptions of Alzheimer patients' personality traits: temporal stability and sensitivity to change. AB - Caregivers of Alzheimer's disease patients provided characterizations of the patients' premorbid personality traits and current personality traits on two occasions nearly 1 year apart. Characterizations of pre-illness personality traits did not differ between the two assessments. Changes in personality over the year were found for neuroticism, extraversion, and conscientiousness. The findings support the reliability of observer's descriptions of premorbid personality using the NEO-PI and the sensitivity of the instrument to personality change in dementia. PMID- 7986487 TI - Swallowing in Alzheimer's disease. AB - Using a prospective case series design, we examined the incidence of oropharyngeal swallowing abnormalities in 25 patients with moderate or severe Alzheimer's disease by videofluoroscopy. Aspiration occurred in 6 of 25 (28.6%). Only four patients showed unequivocally normal performance. Exploratory statistical analyses showed that swallowing abnormalities associated significantly with duration of dementia, eating dependency, and abnormal oral praxis. We observed a trend toward a higher incidence of aspiration in patients with more severe dementia. We conclude that oropharyngeal swallowing abnormalities, including aspiration, are more prevalent in patients with Alzheimer's disease than in normal elderly individuals. PMID- 7986488 TI - Ceruloplasmin is increased in cerebrospinal fluid in Alzheimer's disease but not Parkinson's disease. AB - Although the pathophysiology of Alzheimer's disease (AD) and Parkinson's disease (PD) is unknown, altered brain antioxidative mechanisms have been found in both disorders. Ceruloplasmin (CP) and transferrin (TF) interact to limit concentrations of free ferrous iron (Fe2+), and thus play an important role in antioxidant defense in serum; both proteins are also produced in brain, where their significance as antioxidants is unknown. We quantified concentrations of CP and TF by immunoassay in AD (n = 17) and PD (n = 12) cerebrospinal fluid (CSF) to determine whether these proteins could serve as disease markers. CP was increased versus aged normal subjects (n = 11) in AD (p < 0.05) but not PD CSF, whereas TF concentrations did not differ between groups. CP levels have been reported to be elevated in some brain regions in AD, and increased CP in AD CSF may reflect this finding. Systemic inflammation and oxidative stress are major factors stimulating hepatic CP synthesis, and it remains to be determined whether increased CP concentrations in AD CSF and brain follow from similar mechanisms. PMID- 7986489 TI - D-cycloserine treatment of Alzheimer disease. AB - Degeneration of cortical glutamatergic projections may contribute to the cognitive decline in Alzheimer disease (AD). To evaluate whether 1glutamate system stimulation might confer symptomatic benefit, we administered D cycloserine, a putative partial indirect agonist at certain N-methyl-D-aspartate (NMDA) glutamate receptors, to 12 patients with probable AD. The patients (seven men, five women) had a mean age of 65 +/- 8.4 years; Mini Mental State Examination scores ranged from 15 to 25. A dose escalation phase, in which cycloserine was given in daily oral doses from 25 to 500 mg (total of six dose levels, 1 week per dose), was followed by a "best dose" crossover comparison with placebo under double-blind conditions. The crossover phase consisted of 2 weeks of cycloserine and 2 weeks of placebo, separated by a 1-week washout period. We observed no significant or consistent effect on neuropsychological outcome measures. The results suggest that short-term potentiation of NMDA-mediated glutamatergic transmission may not prove useful in the symptomatic treatment of Alzheimer dementia. PMID- 7986490 TI - An ERP study of expectancy violation in face perception. AB - Expectancies about face-structure can be induced by viewing parts of faces, which generates constraints due to two types of knowledge: feature-content and configuration. In a first experiment ERPs were recorded when parts of familiar faces were completed with incongruent features (from another face), as opposed to congruent features (from the same face). All features were in the correct configuration. An enhanced negativity was found for incongruent completions (N374) that was larger over the right side of the scalp. This replicates the results of Valdes-Sosa and Bobes (1990). In another two experiments, ERPs were recorded when parts of familiar faces were completed by congruent features, but sometimes placed in an incorrect position. In one experiment the features were jumbled; in the other, the features were slightly displaced. These configuration distortions were associated to late positive components, with a maxima at the centro-parietal region, of equal amplitude for both kinds of configuration anomalies. The N374 component seems to be a non-linguistic analog of the N400. The different ERP signatures for expectancy violations of configuration and feature-content suggest that these types of information are processed separately at some stages. PMID- 7986491 TI - Further characterization of the executive memory impairment following frontal lobe lesions. AB - In this article we describe a 41-year-old man who, following an operation to repair a ruptured anterior communicating artery aneurysm, manifested the "hallmark" features of a dysexecutive memory impairment. Of particular note was the patient's apparently normal level of recognition memory but impaired recall on tasks matched for difficulty in control subjects. However, further testing revealed that the patient's recognition memory was not normal under all circumstances. Implications of these data for the interpretation and further investigation of the dysexecutive deficit are discussed. PMID- 7986492 TI - Picture comprehension in probable Alzheimer's disease. AB - Patients with probable Alzheimer's disease (pAD) are frequently said to be compromised at a semantic level of picture comprehension. In order to test this hypothesis, pAD patients were asked to judge whether pictures are instances of a familiar superordinate category ("vegetable"). The targets (e.g., corn) varied in their representativeness, and the foils were either "coherent" items that were not target exemplars (e.g., apple, chair) or "anomalous" items displaying specific features that disqualified the stimuli as target exemplars (e.g., striped carrot). We also asked patients to judge a comparable set of words to determine whether difficulty appreciating pictures is material-specific. pAD patients were impaired at judging target pictures and a subset of picture foils, according to group-wide analyses, although they also encountered some difficulty judging the category membership of words. Individual patient analyses revealed that some patients were equally impaired at judging pictures and words. In particular, one subgroup experienced significant difficulty distinguishing coherent foils related to the target from true exemplars, and this occurred when the foils were presented as either pictures or words. An item-by-item analysis revealed highly concordant difficulty judging the same concepts expressed as either pictures or words in these patients. A material-specific deficit was evident in other pAD patients that resulted in selectively compromised picture judgments, including essentially all types of picture foils. We discuss these profiles of picture comprehension difficulty and conclude that deficits in understanding pictures in pAD may be due to semantic or perceptual types of impairment. PMID- 7986493 TI - Visual field influence on radial line bisection. AB - An attentional bias toward far peripersonal space has been proposed as the mechanism underlying inaccurate bisection of lines oriented radially in the sagittal plane. The position of stimuli in the visual scene has also been proposed as an important determinant of visual attention. This study was designed to evaluate the relative contributions of spatial and visual field factors in bisection of radial lines. The usual linkage of distant space and upper visual field was dissociated by assessing line bisection above eye level. Ten normal subjects bisected twelve 20-30-cm lines 35 cm above eye level and the identical stimuli 35 cm below the eyes. The previous findings of misbisection of radial lines distant to true center was replicated when stimuli were presented below eye level. Lines above eye level were misbisected significantly closer to the subjects. The findings suggest that visual field position influences the allocation of attention in the radial axis of space. PMID- 7986494 TI - Ultrastructure of Reissner's membrane in the rabbit. AB - The ultrastructure of Reissner's membrane in the rabbit is described following vascular perfusion-fixation of live, anesthetized and artificially respirated healthy animals. A new and improved technique of fixation is employed that includes a pressure feedback controlled peristaltic pump and an oxygen-carrying fixative. In ultrathin sections capillaries were observed between the two cell layers comprising Reissner's membrane. The mesothelial cells facing the scala vestibuli were connected by junctional complexes and neither pores nor discontinuities were observed in the cell layer. In the epithelial cells a well developed tubulocisternal endoplasmic reticulum (TER) was noted. Computerized three-dimensional reconstruction documented the continuity of this TER, from prominent disc-shaped subsurface cisterns lining the luminal cell membrane to smaller subsurface cisterns lining the abluminal and lateral cell membranes, forming a transcellular canalicular pathway. The possible function of the TER in Reissner's membrane is discussed with reference to endolymph/perilymph homeostasis. PMID- 7986495 TI - In vitro growth and collagen synthesis in fibroblasts from the rabbit middle ear mucosa. AB - The present methodological study was undertaken to introduce a model system in which individual cells of the middle ear mucosa could be studied under controlled conditions allowing standardized sampling and different manipulations using quantitative methods. The method is based upon isolation and culture of fibroblasts from normal rabbit middle ear mucosae. The growth pattern of the cells was determined by measurement of the total content of cell protein, DNA content and cell division activity. Collagen synthesis was also estimated and results compared with normal skin fibroblasts. Finally, fibroblasts derived from rabbit middle ear mucosae with otitis media were cultured under similar conditions. Results demonstrated the method to be valid and reproducible. Evaluated by any of the parameters applied, growth initially increased exponentially, followed by a stationary phase with a constant cell mass. The growth potentials in middle ear fibroblasts appeared to differ significantly from skin fibroblasts. Except for a decreased cell proliferation, fibroblasts from diseased mucosae did not demonstrate any major differences from the normal fibroblasts probably because the original inflammatory stimuli in vivo were lost in vitro. These findings suggest that future investigations of a model system of otitis media in vitro require the addition of inflammatory mediators. PMID- 7986496 TI - Treatment of lingual tonsillitis by transoral CO2 laser endoscopy. AB - The authors report on their clinical experiences concerning 100 cases of chronic lingual tonsillitis. The surgical treatment employed was endoscopic vaporization of affected tissues with the CO2 laser. Prior to surgical intervention, predisposing conditions such as allergy, rhinosinusitis, and gastroesophageal reflux were identified and treated. The surgical technique consisted of progressive vaporization of the lymphoid tissue at the base of the tongue until the lingual fascia was reached. A slightly defocused (700 mm) continuous 10-15 W laser beam was used at a working distance of 400 mm. Following surgery, no dyspnea was observed secondary to epiglottic edema and only one patient required postoperative hemostasis. Symptoms related to tonsil or tongue inflammation were eliminated or alleviated in 87 patients, remained unchanged in 12 patients and were worse in 1 patient. PMID- 7986497 TI - Kinocilia in the developing stria vascularis of the rat pup. AB - The mammalian stria vascularis undergoes certain developmental changes in the postnatal rat. The present study was designed to examine the ultrastructure of the stria vascularis in rat pups from immediately after birth to 20 days postpartum. The cochlea were removed with the animals under xylazine (Rompun) anesthesia and were prepared for transmission electron microscopy. Each of the three cell types in the stria were found to contain kinocilia up until 12-17 days of age. The presence of kinocilia in the intermediate and basal cells has not been previously described. Findings suggest that these organelles may serve a motile and/or sensory function to assist in the maturation of cell functions, particularly ion transport, during early stages of development. PMID- 7986498 TI - Botulinum toxin treatment in patients with hemifacial spasm. AB - Hemifacial spasm is nearly always a unilateral disease of the facial musculature and is characterized by involuntary tonic or clonic cramps that considerably reduce the affected patient's quality of life. In the past, a number of different conservative and operative therapeutic procedures have been applied for the treatment of hemifacial spasm. In many cases these attempts failed to control the disease permanently or resulted in unwanted, sometimes strong, side effects. We report our own experiences with botulinum therapy in 29 patients with hemifacial spasm (78 therapeutic sessions). In our patients the mean duration of an effect after treatment with botulinum toxin was 18.2 weeks. Side effects were rare. Our results since 1990 at the University of Gottingen demonstrate that subcutaneous application of toxin from Clostridium botulinum to involved facial muscles represents a reliable method for successful treatment of hemifacial spasm. PMID- 7986499 TI - Antigen non-specific immunological tests in progressive sensorineural hearing loss. AB - The purpose of the present study was to determine the validity of antigen non specific immunological tests in order to develop a risk-clinical profile of patients with immune-mediated inner ear pathology. The study was carried out on 38 patients with progressive sensorineural hearing loss and a control group of 26 subjects. Serological testing was used to determine cell activation complexes. In patients with hearing loss, T-lymphocyte subpopulations were found to have an increase in cytotoxic T-cells when compared to T-helper, but only for interleukin 2 receptor expression. This difference was significant between patients and the control group. Present findings suggest that T-lymphocyte "early" marker is of particular interest for developing a risk-clinical profile of patients with sensorineural progressive hearing loss of immune origin. PMID- 7986501 TI - Local interferon therapy for lip carcinoma. AB - In a prospective non-randomized study 21 patients with lower lip squamous cell carcinoma were treated with human natural leukocyte interferon (HNLI). The response rate was measured by a size reduction of more than 25% and was 81%. A complete response rate was considered to be a cure according to histopathological and clinical findings and was 48%. The response rate of six lower lip squamous cell carcinoma cases treated with recombinant interferon alpha 2c was 67% and the complete response rate was 17%. Three patients with basal cell carcinoma of the upper lip were also treated with HNLI. All three patients were cured, as determined by histopathological and clinical findings. These findings indicate that interferon can be a useful alternative therapy for lip carcinoma either with or without surgery. PMID- 7986500 TI - Intravascular hypercoagulability in patients with recent Bell's palsy. AB - Eighty-four patients were examined for blood coagulability during the acute phase of Bell's palsy. Abnormally high levels of thrombin-antithrombin III complex (TAT) and alpha-2 plasmin inhibitor-plasmin complex (PIC) were found, with these increases statistically significant. Values tended to be higher in patients within 3 days after occurrence of the palsy when compared to values in patients 4 days or more later. Abnormal TAT and PIC levels in the acute phase then tended to become normalized during the convalescent phase of the disease. These findings indicated that activation of intravascular coagulability had occurred, with patients entering a temporary clot-forming state. Among the several hypotheses for the etiology of Bell's palsy, our findings support a circulation disorder as an influential factor. PMID- 7986503 TI - Atypical oral presentation of herpes simplex virus infection in a patient after orthotopic liver transplantation. AB - An atypical oral presentation of herpes simplex virus infection in a 49-year-old woman after orthotopic liver transplantation is reported. Clinically, the differential diagnosis included chronic hyperplastic candidiasis, nodular leukoplakia of undetermined etiology, and malignant neoplasm. An excisional biopsy revealed herpesvirus infection, and immunoperoxidase staining confirmed herpes simplex virus infection. This report describes the clinical and histologic appearance of these lesions and the course and treatment of the patient. PMID- 7986502 TI - High-resolution computed tomography of the temporal bone of the Macaca mulatta monkey. AB - High-resolution computed tomography (CT) slices of the temporal bone of the Macaca mulatta monkey were performed and key anatomical landmarks were identified and labelled. The scans provided detailed anatomical definition of the monkey temporal bone and were considered a useful basis for studying the anatomy of a primate model. PMID- 7986504 TI - Pleomorphic adenoma of the larynx. AB - Tumors arising from minor salivary glands are extremely rare neoplasms in the larynx. Of the few reports of pleomorphic adenomas in this site, most have subglottic locations while only one case has involved the true vocal cord and seven cases have had supraglottic locations. We present a case of benign mixed tumor located in the posterior commissure which, to our knowledge, is the first reported in the world literature. PMID- 7986506 TI - Principles of cost analysis. AB - In medicine, reimbursement changes that block cost shifting are rendering revenue based strategies less productive. Under these conditions, cost-benefit and cost effective analyses are being touted as more effective financial tools. The anesthesia literature reflects misunderstanding and misapplication of the terminology, and principles of cost analysis are reviewed in this essay. Current evidence suggests that anesthesia costs are a minor part of the problem of controlling health care expenditures. However, the ability to perform cost analysis is essential for anesthesia groups to secure their position in health care. PMID- 7986505 TI - Cost containment in the operating room: who is responsible? PMID- 7986507 TI - Costs incurred by outpatient surgical centers in managing postoperative nausea and vomiting. AB - STUDY OBJECTIVE: To estimate the financial costs incurred by outpatient surgical centers in managing postoperative nausea and vomiting (PONV). DESIGN: Prospective, observational study. SETTING: 6 hospital-based outpatient surgery centers. PATIENTS: 211 adult patients undergoing outpatient surgery for laparoscopy, dilatation and curettage, knee arthroscopy, or hernia repair. MEASUREMENTS AND MAIN RESULTS: Of the 211 patients studied, 34 experienced PONV in the recovery room. For those patients experiencing PONV, personnel, supply, and drug costs for management of this condition averaged $14.94 per patient. In addition, PONV increased the centers' operating costs by delaying patient discharge by an average of 24 minutes. A minimum estimate of this cost, based on nurses' wage rates, was $7.12. This estimate is appropriate only for short-run considerations in outpatient surgery centers that operate at low capacity. An appropriate valuation for long-run considerations and for centers operating near capacity is based on the revenue that centers lose as a result of extended stays. Lost revenue was estimated to be $415 per patient experiencing PONV. CONCLUSIONS: PONV substantially increases the costs incurred by outpatient surgical centers. PMID- 7986508 TI - Cost-effectiveness analysis of antiemetic therapy for ambulatory surgery. AB - STUDY OBJECTIVE: To compare the relative cost-effectiveness ratios of (1) therapy with ondansetron, droperidol, and metoclopramide in the prevention of postoperative nausea and vomiting (PONV), and (2) prophylactic versus rescue therapy of PONV with these agents. DESIGN: Cost-effectiveness analysis based on the estimated costs of 12 mutually exclusive outcomes identified by decision analysis. SETTING: Computer model of outcome established using data extracted from published studies and a survey of current practice in two university affiliated hospitals. PATIENTS: Patients undergoing operations associated with a high risk of PONV. INTERVENTIONS: The cost-effectiveness of prophylactic antiemetic therapy was compared among three drugs and also compared with limiting treatment to established PONV. MEASUREMENTS AND MAIN RESULTS: Direct costs included drug acquisition, drug delivery, equipment used in managing vomiting, and additional nursing time costs. Indirect costs included drugs and materials used to treat persistent nausea and/or vomiting and the side effects of prophylactic drugs, increased time spent in the postanesthesia care unit, unanticipated hospitalization, and lost earnings due to hospitalization. Separate models were created for patients with both nausea and vomiting and with isolated nausea. The total incremental costs associated with the prophylactic use of ondansetron, metoclopramide, and droperidol were $37.74, $28.43, and $18.17 per patient, respectively. The costs per emesis-free patient with the prophylactic use of ondansetron, metoclopramide, and droperidol, were $55.91, $71.08, and $30.15, respectively, and per nausea-free patient $68.93, $82.74, and $33.52, respectively. Prophylactic antiemetic therapy was cost-effective for operations with a high frequency of emesis, whereas treatment of established symptoms was more cost-effective when the frequency was lower. For ondansetron, prophylactic use was cost-effective only when the frequency of emesis exceeded 33%, whereas prophylactic droperidol was cost-effective even if the frequency was 10%. CONCLUSIONS: When drug costs, efficacy, and adverse events were all considered, prophylactic droperidol was more cost-effective than ondansetron, and both drugs were more cost-effective than metoclopramide. However, the expected frequency of PONV, as well as local drug acquisition costs, can significantly influence whether a particular antiemetic is cost-effective when given prophylactically or only as therapy for established PONV. PMID- 7986509 TI - Impact of a cost containment program on the use of volatile anesthetics and neuromuscular blocking drugs. AB - STUDY OBJECTIVE: To determine the impact of a cost containment program on the use of volatile anesthetics and neuromuscular blocking drugs. DESIGN: Historical, controlled, retrospective analysis. SETTING: Main operating rooms of an adult general hospital at a university medical center. PATIENTS: All patients undergoing anesthesia between July 1991 and November 1993. MEASUREMENTS AND MAIN RESULTS: Cost per case was determined by dividing the monthly expenditure for each class of drug by the caseload for that month. Cost per case of volatile anesthetic drugs decreased from $19.20 +/- 1.16 to $15.16 +/- 0.39 (p = 0.0034 by unpaired t-test). For neuromuscular blocking drugs, cost per case decreased from $19.67 +/- 1.35 to $12.23 +/- 0.66 (p = 0.003). CONCLUSIONS: Concerted educational efforts can decrease the per case expenditures for both volatile anesthetic drugs and neuromuscular blocking drugs. PMID- 7986510 TI - Economic considerations in the use of neuromuscular blocking drugs. AB - The acceptance of new and increasingly expensive technologies is a major component of the rising costs of health care. While the practice of anesthesia has been relatively immune from the effects of cost containment, it is inevitable that practitioners will have to justify costly practices. Available pharmacoeconomic methods can be applied to the use of all anesthetic drugs, particularly neuromuscular blocking drugs. Cost-effectiveness analysis allows the practicing anesthesiologist to prioritize the use of neuromuscular blocking drugs to maximize their benefit while reducing unnecessary costs. PMID- 7986511 TI - Practical methods of cost containment in anesthesia and surgery. AB - With the increasing focus of national attention on health care and health care costs, anesthesiologists, along with all other medical specialists, must become more cost conscious in their practice behaviors. This review describes the current concerns about health care in the United States, including a discussion of some of the forces causing the increase in health care spending. The role of anesthesiology in the increase in health care costs is discussed. Practical methods for controlling anesthesia costs are outlined, including reducing preoperative testing, decreasing blood product use, and employing more regional and local anesthetic techniques. Several ideas for reducing the costs of anesthetic gases and drugs, including low-flow anesthesia and less expensive alternative drugs, are presented. The final section describes the changes in anesthesia drug use that occurred from 1992 to 1993 at one health care center (St. Francis Regional Medical Center, Wichita, KS, which is associated with the University of Kansas School of Medicine-Wichita). These changes resulted in a 13% reduction in anesthesia drug costs, which amounted to a savings of $127,472. The largest decreases were in anesthetic gases (16%), resulting from an increase in the use of low-flow techniques, and in muscle relaxants (26%), resulting from a switch to older lower-cost drugs. PMID- 7986512 TI - Cost-effective use of operating room supplies based on the REMEDY database of recovered unused materials. AB - It is estimated that $200 million worth of prepared materials are discarded unused in operating rooms in the United States each year. Although some of these materials have been successfully recovered for overseas donation, they nevertheless constitute an undesirable burden on health care efficiency. This situation has prompted a reevaluation of the procedures that result in the overpreparation of surgical supplies, in the hope of reducing hospital, patient, and third-party payer expenditures. A database, which was initially developed to track the overseas donation of recovered supplies from Yale-New Haven Hospital, is now being applied to measure approaches to waste reduction. This report summarizes the application of this database to an integrated program designed to modify nursing procedures and physician prespecified supply lists. PMID- 7986513 TI - Operating room start times and turnover times in a university hospital. AB - STUDY OBJECTIVE: To measure the start time for the first case of the day and the turnover times for subsequent cases in the operating rooms (ORs) at an academic hospital. DESIGN: Prospective study. SETTING: ORs at a university medical center. PATIENTS: All patients undergoing an operative procedure that started between 7 A.M. and 5 P.M. weekdays for the period January 1, 1989, through June 30, 1989. INTERVENTIONS: For each patient, the following times were recorded: OR ready, patient enters OR, anesthesia induction complete, surgery start, surgery end, patient leaves OR. MEASUREMENTS AND MAIN RESULTS: Patients were brought into the OR just before the scheduled start time. Surgical incision was made 21 to 49 minutes after the patient was brought into the OR. Room turnover time (time from patient in to patient out) was almost uniformly 36 minutes. Patient turnover time (time from end of surgery in one patient to end of induction of next patient) was generally 1 hour. Turnover times were shorter for those ORs in which primarily monitored anesthesia care was provided and longer in ORs in which patients routinely required invasive monitoring. CONCLUSIONS: The scheduled start time for the first case of the day was generally the time the patient was brought into the OR. Because of the variable amount of time required for anesthesia induction and surgical preparation and draping, incision occurred 21 to 49 minutes later. The time between cases when no surgery was occurring was significantly longer than room turnover time because of the need to wake up one patient and induce the following patient. Because of a lack of standardized definitions, there is probably a strong perceptual difference among anesthesiologists, OR nurses, and surgeons when viewing start and turnover times. At our own teaching institution, shortening turnover times would increase the amount of elective OR time available, but the impact would not be significant because the number of procedures done per OR each day is low. PMID- 7986514 TI - Cost containment in anesthesiology: a survey of the association of anesthesia clinical directors. PMID- 7986515 TI - Does the design of the Sprotte spinal needle reduce the force needed to deform the tip? AB - STUDY OBJECTIVE: To determine whether the window design of pencil-point spinal needles leads to deformation under lateral or axial loading conditions. DESIGN: Independent-measure, multigroup study of the force required to deform needles. SETTING: Independent testing laboratory. MEASUREMENTS AND MAIN RESULTS: The force necessary to bend 22- and 24-gauge Sprotte, 22- and 25-gauge Whitacre, and 22- and 25-gauge Quincke needles was measured using an Instron gauge (Instron Corp., Canton, MA) after microscopic verification of needle uniformity. Effects of lateral and axial forces were evaluated in separate experiments. The force needed to bend the Sprotte needles was less than that needed for the Whitacre and Quincke needles of similar size when lateral or axial pressure was applied. Microscopic inspection of the needles showed a marked variability in the window area placement in a single lot of Sprotte needles. Examination of the needle tips demonstrated that the Sprotte needles were most likely to bend at the needle window, while the Quincke and Whitacre needles deformed at the point of clamping. CONCLUSIONS: The Sprotte needles have an inherent design weakness to lateral and axial pressure, which may result in a greater number of needle tip deformations upon needle insertion. The nature of this deformation may result in difficulty in needle withdrawal and possibly fracture of the needle tip. PMID- 7986517 TI - Evaluation of the efficacy of a forced-air warmer (Bair Hugger) during spinal surgery in children. AB - STUDY OBJECTIVE: To evaluate the efficacy of a forced-air warmer during spinal surgery for correction of scoliosis in children. DESIGN: Prospective randomized study (group allocation based on the availability of the warming device). SETTING: Children's teaching hospital. PATIENTS: 51 ASA physical status I and II children (mean age, 15 years; mean weight, 45 kg) scheduled for posterior spinal fusion with general anesthesia. INTERVENTIONS: Study group (warmed; n = 26)--legs covered with the forced-air warmer (Bair Hugger, Augustine Medical, Inc., Eden Prairie, MN) after installation of the patient in prone position--versus control group (n = 25)--400W heat lamp placed over the head during surgery as is usually done in our institution. MEASUREMENTS AND MAIN RESULTS: Rectal temperature was taken every 15 minutes during surgery and during the first 2 hours in the recovery room. Time required for the wake-up test, time to extubation, and blood loss also were noted. Temperature profiles were very different in the 2 groups. In the control group, rectal temperature decreased during the first 180 minutes to a minimum of 34.8 degrees C +/- 0.6 degrees C, followed by a slow rewarming phase. In the warmed group, the lowest temperature (35.6 degrees C +/- 0.5 degrees C) was recorded 45 minutes after placement of the forced-air warmer, followed by an effective warming phase. At the end of surgery, temperature was significantly higher in the warmed group than in the control group (36.5 degrees C +/- 0.8 degrees C vs. 35.4 degrees C +/- 0.9 degrees C). However, time required for the wake-up test, time to extubation, and blood loss did not differ between groups. CONCLUSION: The forced-air warmer (Bair Hugger) is effective during spinal surgery, although only about 20% of body surface area can be covered. PMID- 7986516 TI - Effects of subcutaneous verapamil on the duration of local anesthetic blockade. AB - STUDY OBJECTIVES: To determine whether a subcutaneous injection of verapamil will provide local anesthesia and whether a mixture of lidocaine and verapamil will prolong the anesthetic effect of lidocaine alone. DESIGN: Randomized, double blind, placebo-controlled study. SETTING: Preanesthetic area of a large metropolitan teaching hospital. PATIENTS: 20 volunteers. INTERVENTIONS: All volunteers received 4 injections of normal saline, verapamil, lidocaine, and lidocaine-verapamil at the volar aspect of the forearm. The sites were tested with a 26-gauge needle to be sure the sensation of sharp could be appreciated. The injections were performed in a randomized, double-blind fashion using a sterile technique. The 4 areas were tested at 1-minute intervals using a 26-gauge needle until the sensation of sharp was again perceived. MEASUREMENTS AND MAIN RESULTS: Injection sites were examined for the presence and degree of erythema. Volunteers were asked to rate the degree of pain felt during and immediately after injection. The time elapsed until the person was again able to perceive sharp from a 26-gauge needle prick was measured at all 4 sites. When compared with the effects of normal saline, subcutaneous verapamil provided local anesthesia to pinprick. The mixture of verapamil and lidocaine also provided anesthesia to pinprick, but the duration of effect was less than that provided by lidocaine alone. The use of verapamil alone and in combination with lidocaine was associated with a marked degree of erythema and edema. CONCLUSIONS: Verapamil injected subcutaneously provides a degree of local anesthesia. However, this effect is hampered by a local reaction at the injection site and a short duration of action. The mixture of lidocaine and verapamil provides a shorter duration of action than does lidocaine alone. PMID- 7986518 TI - Comparative pharmacokinetics of oral versus sublingual clonidine. AB - STUDY OBJECTIVE: To compare the pharmacokinetic and pharmacodynamic profile of orally versus sublingually administered clonidine. DESIGN: Randomized, crossover, nonblinded, open-label study. SETTING: University tertiary-care center. PATIENTS: 10 healthy male and female volunteers aged 20 to 42 years. INTERVENTIONS: A heparinized catheter was placed intravenously for blood-sampling purposes. An automatic sphygmomanometer was placed on the volunteers' left upper arm to obtain systolic and diastolic blood pressure, and a pulse oximeter was placed on the right index finger to measure heart rate (HR). MEASUREMENTS AND MAIN RESULTS: Serial blood samples were collected throughout the 24-hour study period to determine clonidine concentrations. The effect of clonidine on blood pressure (BP) and HR also was measured. The half-life, area under the curve, maximum concentration, and time to reach maximum concentration were similar for both the sublingual and oral routes. BP and HR changes were similar for both sublingual and oral clonidine. CONCLUSION: Both routes of administration resulted in similar pharmacokinetic and pharmacodynamic profiles. Attempts to shorten clonidine's latency with sublingual administration were unsuccessful. Our study shows that a single dose of clonidine 0.3 mg has the same pharmacokinetic and dynamic profile when administered orally or sublingually. Therefore, the sublingual route can be predictably used in fasting patients, those having difficulty swallowing, or those who are unable to absorb drugs through the gastrointestinal tract; the sublingual dose is the same as the oral dose. PMID- 7986519 TI - Postoperative acute respiratory failure following thoracotomy in a patient with Charcot-Marie-Tooth disease. AB - We present the case of a patient with Charcot-Marie-Tooth (CMT) disease who required prolonged ventilatory support following a thoracotomy due to respiratory muscle weakness. Although CMT was traditionally believed to affect only skeletal muscles, recent evidence suggests that respiratory involvement is relatively common, even in the absence of pulmonary symptoms. Assessment of respiratory muscle strength using measurements of vital capacity and negative inspiratory force is helpful in evaluating pulmonary reserve in patients with CMT. PMID- 7986520 TI - Closed head injury and the treatment of sequelae after a motor vehicle accident. AB - Approximately 2 million closed head injuries (CHIs) occur yearly in the United States. Twenty-five percent of these injuries require hospitalization, and 70,000 to 90,000 of those hospitalized suffer long-term disability. This case conference details one such case of CHI in which the patient ultimately died. Close attention is given to the pathophysiology and treatment of this process. Commonly accepted, as well as investigational, modalities of therapy are discussed. PMID- 7986522 TI - The laryngeal mask airway in elective difficult intubation. PMID- 7986521 TI - The experience of complete neuromuscular blockade in awake patients. PMID- 7986523 TI - Anaphylactic reaction to contrast in the ureter versus absorption through a percutaneous nephrostomy site. PMID- 7986524 TI - The laryngeal mask airway for outpatient anesthesia. PMID- 7986525 TI - Post-translational protein import and folding. AB - Significant advances have been made over the past year in analyzing the membrane machineries for the post-translational export of proteins in bacteria and for the import of proteins into mitochondria. Another important development is the identification in mitochondria of homologs of the bacterial heat-shock proteins DnaJ and GrpE, which function together with Hsp70 in membrane translocation and folding of imported proteins. A number of gene products involved in peroxisomal protein uptake have been identified, which are now awaiting biochemical analysis. PMID- 7986526 TI - Protein translocation across the endoplasmic reticulum. AB - In the past year, dramatic progress has been made in our understanding of protein biogenesis at the initial steps of the eukaryotic secretory pathway. New insights have refined our view of protein targeting to the endoplasmic reticulum membrane and provided the best glimpse so far of the subsequent translocation step. The interactions of three GTP-binding proteins have been found to result in a novel cycle of GTP binding and hydrolysis to regulate protein targeting. Experiments with fluorescent probes have revealed that the nascent chain enters an aqueous environment within the membrane sealed off from the cytosol. In vitro reconstitution experiments have shown surprising simplicity in the number of polypeptides required to facilitate translocation across a synthetic membrane and to promote the integration of membrane proteins. Furthermore, new genetic and functional similarities between divergent organisms have been discovered, providing convincing evidence of the evolutionary conservation of strategies used in the targeting and translocation of polypeptides. PMID- 7986527 TI - Retention and retrieval in the endoplasmic reticulum and the Golgi apparatus. AB - Resident proteins of the exocytic pathway contain at least two types of information in their primary sequence for determining their subcellular location. The first type of information is found at the carboxyl terminus of soluble proteins of the endoplasmic reticulum (ER) and in the cytoplasmic domain of some ER and Golgi membrane proteins. It acts as a retrieval signal, returning proteins that have left the compartment in which they reside. The second type of information has been found in the membrane-spanning domain of several ER and Golgi proteins and, though the mechanism by which it operates is still unclear, it acts as a retention signal, keeping the protein at a particular location within the organelle. The presence of both a retrieval signal and a retention signal in a trans-Golgi network resident protein suggests that more than one mechanism operates to ensure correct localization of resident proteins along the exocytic pathway. PMID- 7986528 TI - Rab GTPases: master regulators of membrane trafficking. AB - Rab GTPases are thought to be likely to catalyze the accurate association of pairs of targeting molecules located on the surfaces of transport vesicles with their corresponding membrane acceptors. Advances during the past year have solidified our understanding of the mechanisms by which Rab proteins are recruited onto nascent transport vesicles and retrieved from their fusion targets. Functional analyses of Rab proteins in living cells have led to the surprising observation that vesicles do not seem to form if the appropriate Rab protein, in its GTP-bound conformation, is not present. PMID- 7986529 TI - ARF: a key regulatory switch in membrane traffic and organelle structure. AB - The small GTP-binding protein ADP ribosylation factor (ARF) regulates, through a GTP cycle, the reversible binding of cytosolic coat proteins to Golgi membranes. By determining the binding and release of coat proteins from membranes, ARF controls the production and lifetime of coated-membrane structures. In the past year, studies suggesting a role for ARF in phospholipid metabolism have broadened our perspective on ARF function within the cell. PMID- 7986530 TI - Coat proteins in intracellular membrane transport. AB - Transport of newly synthesized material from the endoplasmic reticulum (ER) towards the Golgi complex, through the Golgi cisternae, and out of the trans Golgi network (TGN) is thought to be mediated by vesicular carriers. Different types of vesicle are involved in this biosynthetic membrane traffic. All are coated with protein complexes on their cytoplasmic surface. COP-coated vesicles have recently been implicated in transport of cargo from the ER to the TGN, and clathrin-coated vesicles from the TGN to endosomes, but the carriers moving material to the cell surface are still unknown. Sequence homologies between subunits of the COP- and the clathrin-adaptor complexes suggest that coat proteins may belong to a family of proteins with related functions. The precise role of the coat proteins is not fully understood, although they have been implicated in clustering of cargo into buds and in budding of vesicles. In addition, coat proteins may play an essential role in targeting of transport intermediates and may serve to regulate membrane fusion. PMID- 7986531 TI - The role of clathrin, adaptors and dynamin in endocytosis. AB - Clathrin-coated vesicles bud from the plasma membrane and from the trans-Golgi network; both populations of coated vesicles participate in the endocytic pathway. Coated-vesicle formation is initiated by the binding of cytosolic adaptor complexes to putative adaptor receptors on the appropriate membrane. Clathrin then binds to the adaptors and assembles to form a coated bud, which pinches off as a coated vesicle. The GTPase dynamin facilitates the formation of coated vesicles at the plasma membrane through an as yet unknown mechanism. Recent studies suggest that regulatory mechanisms may operate at each of these stages. PMID- 7986532 TI - Mechanisms of cell polarity: sorting and transport in epithelial cells. AB - The recent discovery of widely distributed targeting determinants, which govern the polarized cell-surface distribution of plasma membrane proteins in epithelial cells, has significantly changed our view of how polarized cells generate functionally distinct membrane domains. Together with the surprising finding that the same determinants are recognized on both the biosynthetic and the endocytic pathways, it now appears likely that a common epigenetic code may exist that controls molecular sorting of membrane proteins in a wide variety of polarized, and perhaps even non-polarized, cell types. PMID- 7986533 TI - Mechanisms of vesicle docking and fusion: insights from the nervous system. AB - Upon stimulation of nerve cells, synaptic vesicles fuse with the presynaptic plasma membrane to release neurotransmitter. The biochemical pathway responsible for synaptic-vesicle docking and fusion is now being elucidated. Many of the proteins implicated in this process have homologs elsewhere in the cell. The docking and fusion mechanism discussed in this review may account for the specificity of vesicular trafficking throughout both regulated and constitutive secretory pathways. PMID- 7986534 TI - Formation of synaptic vesicles. AB - Synaptic vesicles (SVs) are specialized secretory organelles used for the fast and focal signaling between nerve cells. They are small and homogeneous in size (50 nm), and contain non-peptide neurotransmitters such as glutamate, gamma aminobutyric acid (GABA) and acetylcholine. The exocytosis of SVs occurs at low rates in resting nerve terminals and is greatly stimulated by depolarization induced Ca2+ influx. Following exocytosis, SV membranes are rapidly retrieved, refilled locally with neurotransmitters and reused for the assembly of new SVs. Over the past few years, significant progress has been made in characterizing the molecular composition of SVs. From these studies, we know that SVs share a conserved set of membrane proteins with transport vesicles involved in other pathways. Furthermore, these findings have provided us with a new understanding about the evolutionary origin of SVs from recycling vesicles present in all cells. PMID- 7986535 TI - Bacterial transporters. AB - Recent experiments in bacterial systems have established an extended database of sequences broadly relevant to all membrane transporters, allowing serious study of evolutionary relationships. The database will be especially useful in integrating conclusions derived from work with proteins in the major facilitator superfamily, because this kinship includes both eukaryotic and prokaryotic model systems. Even among carriers not linked by evolution, clear hints of functional homology have been note. Advances are also evident in the structural analysis of membrane carriers. Site-directed mutagenesis in a bacterial antiporter has shown how the translocation pathway might be identified; this should complement recent progress in preparing two-dimensional crystals of the eukaryotic anion-exchange protein, band 3. Together, these studies could soon verify or reject the idea that the transport pathway lies at the interface between the amino-terminal and carboxy-terminal helical bundles found in the hydrophobic core of most carrier proteins. If verified, the argument might allow construction of informed three dimensional models in the absence of crystallographic evidence. PMID- 7986536 TI - Mammalian exchangers and co-transporters. AB - In the past year, novel mammalian exchanger and co-transporter isoforms have been characterized. Specialized subdomains within these oligomeric transporters have been shown to be involved in biosynthesis, targeting, transport and regulation. Progress on the structural front has been limited due to the lack of high resolution structures, but transport mutants responsible for disease states continue to be identified. PMID- 7986537 TI - Neurotransmitter transporters: new members of known families. AB - The identification of two gene families encoding neurotransmitter transporters was a major step towards a better understanding of these proteins and their function in neurotransmission. The recent isolation of additional members of these families underscores their high molecular diversity and implies a delicate regulation of transmitter uptake. PMID- 7986538 TI - Molecular physiology of anion channels. AB - Anion channels have diverse functions, ranging from regulation of cell volume to transepithelial transport and control of excitability. Three well established structural classes of plasma membrane chloride channels now exist: the ligand gated chloride channels, the cAMP-stimulated cystic fibrosis transmembrane conductance regulator channel, and the voltage-gated (or swelling-activated) members of the CLC chloride channel family. Genetic defects leading to inherited disease are known for each of these classes. A combination of mutagenesis and biophysical analysis has been used to correlate their structure with function. Recently, the role of several molecules has been questioned; rather than being chloride channels themselves, they may be activators of endogenous channels in the cells used for expression. PMID- 7986540 TI - Membrane permeability. PMID- 7986539 TI - Membranes and sorting. PMID- 7986541 TI - Color Doppler myocardial imaging: a new technique for the assessment of myocardial function. AB - Color Doppler myocardial imaging is a new technique that has been developed specifically to allow color Doppler imaging of myocardial wall motion rather than blood pool imaging. Such a technique has the potential to interrogate velocities, accelerations, and Doppler signal strength within the myocardial wall. Moreover, the concomitant enhancement of the myocardial Doppler signal after an intravenous injection of a transpulmonary echocardiographic contrast agent could permit the noninvasive assessment of regional myocardial perfusion. Thus this new imaging modality could be a valuable adjunct to the ultrasound assessment of myocardial ischemia. PMID- 7986542 TI - Two-dimensional echocardiographic automatic boundary detection for evaluation of left ventricular function in unselected adult patients. AB - Recent modifications in two-dimensional echocardiographic imaging include automatic boundary detection (ABD) that permits instantaneous quantification of left ventricular (LV) function. To define its clinical application from different views in consecutive patients (n = 68), we performed both conventional two dimensional imaging and ABD with lateral gain compensation and compared the ability of each method for visualization of myocardial segments. From each view (short-axis and apical four- and two-chamber), the LV was divided into six wall segments. The short-axis view was obtained successfully in 53 of 68 patients; of the possible 318 segments, 96% were visualized adequately by two-dimensional echocardiography and 89% by ABD. From the four-chamber view, obtained in 63 of 68 patients, visualization of 378 possible segments was 93% by two-dimensional imaging and 86% by ABD, respectively. From the two-chamber view obtained in 58 of 68 patients, the success rate was 88% and 80% (two-dimensional imaging and ABD, respectively). ABD detected LV endocardial/blood borders in all six segments of each view in 73%, 72%, and 72% of cases, concordant with adequate two-dimensional imaging. Discrepancies between two-dimensional imaging and ABD were usually in the short-axis inferior and lateral, four-chamber lateral, and two-chamber anterior segments. There were 46 patients with normal LV wall motion and 22 with wall-motion abnormalities. The average time required to perform ABD was 375 seconds (range 180 to 780 seconds).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7986543 TI - Multifold sonicated dilutions of albumin with fifty percent dextrose improve left ventricular contrast videointensity after intravenous injection in human beings. AB - An intravenous injection of a onefold dilution of sonicated albumin with 50% dextrose improves echocardiographic left ventricular cavitary opacification in dogs compared with sonicated albumin. The objective of this study was to determine whether sonicated dilutions of albumin with dextrose would improve left ventricular videointensity after intravenous injection in humans and to delineate what ratio of albumin with dextrose results in optimal left ventricular cavitary opacification. We gave intravenous injections (randomized) of sonicated albumin and three different dilutions of albumin with 50% dextrose sonicated at different time intervals (onefold, threefold, and sevenfold dilutions sonicated albumin for 40 seconds and threefold and sevenfold dilutions sonicated albumin for 80 to 100 seconds) to 10 healthy human volunteers. End-diastolic and end-systolic videointensity and mean transit time from the mid-left ventricular cavity were compared after an 8.0 ml intravenous injection of all six samples. The threefold and sevenfold dilutions sonicated for 80 to 100 seconds produced microbubble concentrations similar to those of sonicated albumin but with significantly larger (5.6 microns versus 4.7 microns for sonicated albumin) size. These dilutions produced significantly higher end-diastolic and end-systolic videointensity, area under the time-intensity curve, and mean transit time compared with sonicated albumin or any of the dilutions sonicated for 40 seconds (p < or = 0.005). These data suggest that multifold dilutions of albumin with dextrose produce improved ultrasound contrast. PMID- 7986544 TI - Morphology of the mitral valve as displayed by multiplane transesophageal echocardiography. AB - This study was performed to (1) describe how multiplane transesophageal echocardiography (TEE) facilitates imaging of the entire mitral valve apparatus, and (2) prospectively compare the morphology of the different segments of the mitral apparatus as determined by multiplane TEE and direct surgical inspection. The study consisted of 30 consecutive patients examined by multiplane TEE less than 24 hours before mitral valve surgery. The mitral valve was displayed in transgastric and transesophageal views with the imaging planes specifically aligned to demonstrate continuity between the papillary muscles, chordae tendineae, and leaflet edges. The character and location of morphologic abnormalities identified by findings of preoperative TEE were highly concordant with surgical inspection of the valve (p < 0.0001). Thus multiplane TEE offers the ability to visualize the entire mitral apparatus as a functional unit and to identify morphologic abnormalities of the valve correctly. PMID- 7986545 TI - Visual assessment of valvular regurgitation: comparison with quantitative Doppler measurements. AB - To investigate which factors influence visual evaluation and how accurate it is in patients with valvular insufficiency, 83 patients were studied. All were in sinus rhythm, 43 with mitral and 40 with tricuspid regurgitation. Categoric visual grading (mild, moderate, and severe) was compared with jet area method and regurgitant fraction and the factors that influenced the assigned rank were identified. With jet area method (mean of areas in three planes), the correlation with regurgitant fraction was r = 0.61 for free jets and r = 0.32 for wall jets (overall r = 0.47) in patients with mitral regurgitation, and r = 0.81 and r = 0.46 for free and wall jets, respectively, in patients with tricuspid regurgitation (overall, r = 0.65). With visual grading, the correlation was for free and wall jets, respectively, rho = 0.80 and rho = 0.74 (overall rho = 0.76) in patients with mitral regurgitation, and rho = 0.79 and rho = 0.49 for free and wall jets, respectively (overall rho = 0.62), in patients with tricuspid regurgitation. The jet area parameter found to have the most influence on visual grading was the average area in three planes divided by atrial area, with rho = 0.80 and rho = 0.51 in patients with mitral regurgitation (free and impinging jets respectively) and rho = 0.60 and rho = 0.46 in tricuspid regurgitation. We conclude that visual grading of valvular regurgitant jets correlates well with quantitative measures of valvular incompetence and better than any simple jet area method.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7986546 TI - Long-term follow-up of mitral paraprosthetic regurgitation by transesophageal echocardiography. AB - Paravalvular regurgitation (PVR) is an uncommon complication of mitral valve replacement (MVR). Although severe PVR is almost always repaired immediately when recognized during surgery, there are little data available on the management of patients with mild and moderate PVR. This study includes eight patients with mild (n = 6) and moderate (n = 2) PVR identified by transesophageal echocardiography at the time of MVR who were treated conservatively. Clinical and echocardiographic follow-up was obtained at a mean of 16.3 months. Two of six patients with mild PVR at the time of MVR and two of two patients with moderate PVR at the time of MVR deteriorated clinically and echocardiographically over time. We suggest that moderate PVR should be corrected at the time of valve replacement surgery, if this can be performed without high operative risk. Mild PVR should probably also be repaired, if this can be performed at low risk, because some will progress. Patients left with mild PVR after surgery, or patients in whom PVR is recognized only after surgery, should be followed up carefully with serial clinical and echocardiographic examinations. PMID- 7986547 TI - Transthoracic Doppler assessment of pattern of left ventricular dysfunction in hypertensive heart disease: combined analysis of mitral and pulmonary venous flow velocity patterns. AB - Although mitral flow velocity pattern changes with the progression of left ventricular (LV) diastolic dysfunction, it lacks predictive value in individual patients because of pseudonormalization in the presence of congestive heart failure and many physiologic and pathologic contributors to the mitral flow velocity pattern. To determine whether analysis of pulmonary venous flow velocity patterns complements the information obtainable from the mitral flow velocity patterns in the evaluation of patterns of LV dysfunction of hypertensive heart disease in individual patients, the ratio of the peak early diastolic filling velocity/peak filling velocity at atrial contraction (E/A ratio) in the mitral flow velocity pattern and the ratio of the peak systolic forward flow velocity (S)/peak diastolic forward flow velocity (D) (S/D ratio) in the pulmonary venous flow velocity pattern by the transthoracic approach were determined in 107 hypertensive patients with and without congestive heart failure. Age-related normal values of the E/A and S/D ratios were determined in 61 normal subjects and used to judge the normality or abnormality of the patterns. Results of the study indicate that (1) although an increased mitral E/A ratio is strongly indicative of heart failure with normal LV systolic function, the mitral E/A ratio is frequently within the normal range in hypertensive patients with heart failure; (2) association of decreased pulmonary venous S/D ratios with a normal mitral flow velocity pattern indicates the presence of heart failure as a result of LV systolic dysfunction that is usually observed at the most advanced pattern of LV dysfunction; (3) mild LV diastolic dysfunction is likely to exist in patients with normal E/A ratios if the pulmonary venous S/D ratio is higher than normal value; (4) predictive accuracy in the detection of LV systolic and diastolic dysfunction would be improved if both mitral and pulmonary venous flow velocity patterns rather than the mitral flow velocity pattern alone were analyzed. In conclusion, analysis of pulmonary venous flow velocity recordings improves accuracy and reliability of the Doppler assessment of LV systolic and diastolic dysfunction, particularly in individual hypertensive patients with normal mitral flow velocity patterns. PMID- 7986549 TI - A prospective study of left atrial spontaneous echo contrast and thrombus in 100 consecutive patients referred for balloon dilation of the mitral valve. AB - The aim of this study was to determine the clinical, echocardiographic, and hemodynamic predictors of left atrial spontaneous echo contrast (SEC) and thrombus, respectively, in patients referred for balloon dilation of the mitral valve and to establish the relationship between the two phenomena in this group of patients. One hundred consecutive patients (mean age 57 +/- 14 years) referred for mitral balloon (Inoue) dilation were studied prospectively with transthoracic and transesophageal (83 biplane and 17 single plane) echocardiography (TEE) combined with spectral and color Doppler modalities, immediately before the procedure. TEE was repeated within 24 hours of valvotomy in the first 55 patients. All patients also underwent comprehensive left- and right-sided heart catheterization. TEE was performed successfully in 96 patients. SEC was detected in all 65 patients in atrial fibrillation and in 14 (45%) of 31 patients in sinus rhythm. Patients with SEC were significantly older (61 +/- 13 vs 45 +/- 12 years; p < 0.001) and had larger left atrial volume (98 +/- 48 vs 64 +/- 24 ml; p < 0.001), higher mitral valve echocardiographic scores (7.4 +/- 3.2 vs 5.3 +/- 2.6; p = 0.016), lower cardiac output (3.5 +/- 1.1 versus 4.6 +/- 0.9 L/min; p < 0.001), lower peak systolic pulmonary vein flow velocity (SVm) (24 +/- 12 versus 45 +/- 11 cm/sec; p < 0.001), and correspondingly lower systolic velocity-time integral (4.0 +/- 2.6 vs 7.9 +/- 2.9 cm; p < 0.001) than had patients without SEC. There were no significant associations between SEC and either mitral valve area or anticoagulant therapy. SVm and atrial fibrillation were found to be independent predictors of SEC. In patients in sinus rhythm, SVm was the only independent predictor of SEC. After mitral balloon dilation, SEC disappeared in only two of 35 patients in atrial fibrillation and in five of eight patients in sinus rhythm. Significant mitral regurgitation occurred in the two patients in atrial fibrillation. TEE detected left atrial thrombus in 14 patients. Thrombus was significantly associated with age, mitral valve area, and the severity of SEC. The latter was found to be an independent predictor of thrombus. Two patients in sinus rhythm had evidence of left atrial mechanical dysfunction. Both patients had left atrial SEC and one had thrombus in the appendage. It is concluded that SEC in patients with severe mitral stenosis is dependent on left atrial systolic function and peak systolic pulmonary vein velocity. It is not related to mitral valve area or anticoagulant therapy.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 7986548 TI - Assessment of right-to-left shunt flow in atrial septal defect by transesophageal color and pulsed Doppler echocardiography. AB - To investigate the clinical significance and problems of right-to-left (R-L) shunt flow dynamics in atrial septal defects, we performed transesophageal color and pulsed Doppler echocardiography in 30 patients with atrial septal defects of the ostium secundum type. The 30 patients consisted of 20 with a pulmonary artery systolic pressure of less than 40 mm Hg, four with a pressure of 40 to 60 mm Hg, three with a pressure of 90 mm Hg or more, two patients with pulmonic stenosis, and one patient with Ebstein's anomaly. R-L shunting was determined by the presence of a shunt flow signal across the defect during each cardiac cycle. The time of R-L shunt flow was compared with the various parameters obtained by echocardiography and cardiac catheterization. R-L shunt flow signals were detected at the following times: (1) at the onset of ventricular contraction or the closing phase of the tricuspid valve in five patients with isolated atrial septal defect. These patients showed an increase of mean right atrial pressure but had no severe pulmonary hypertension; (2) during ventricular systole in five of 26 patients with tricuspid regurgitation and one patient with Ebstein's anomaly. The tricuspid regurgitant signal was directed toward the ostium of the defect in three patients and was massive in the other patients; (3) during middiastole in three patients without pulmonary hypertension. These patients showed massive left-to-right shunt flow from end systole to early diastole; and (4) during atrial systole in three patients with severe pulmonary hypertension and two patients with pulmonic stenosis. The former, in particular, showed the aliasing signal as a high-speed shunt flow. In two of the three patients with severe pulmonary hypertension, R-L shunting continued from atrial systole to early ventricular systole and was also observed in early diastole. R-L shunt flow was detected in patients with atrial septal defects not only with pulmonary hypertension but also without pulmonary hypertension and was influenced by the right atrial pressure in the phase of tricuspid valve closing, the volume or direction of tricuspid regurgitation, rebound flow caused by massive left-to right shunt flow, the grade of right ventricular distensibility or the complication of pulmonary hypertension, and complications with other cardiac anomalies. Thus R-L shunt flow in patients with atrial septal defects was detected easily by transesophageal color and pulsed Doppler echocardiography because of the high efficiency of this method for its detection. PMID- 7986550 TI - Right atrial and right ventricular obstruction by recurrent stromomyoma. AB - A 30-year-old woman had a history of a uterine fibroid 6 years before admission. She had resection of a right atrial mass diagnosed as a leiomyoma 2 years ago and a second cardiac procedure for recurrent tumor 1 year ago. Pathologic examination at that time indicated that the tumor was a low-grade endometrial stromal sarcoma (stromatosis) with features of benign leiomyoma (intravenous leiomyomatosis). This time she was admitted with facial and lower extremity swelling as well as ascites. Transthoracic and transesophageal echocardiography revealed a large tumor entering the heart from the inferior vena cava and filling the right atrium and ventricle. Lower extremity ischemia from bilateral compartment syndrome due to severe edema developed, and she underwent successful surgical resection of the tumor that filled the right side of the heart, inferior vena cava, and mesenteric and renal veins. PMID- 7986552 TI - Transesophageal echocardiographic artifact mimicking pseudoaneurysm of the aorta. AB - Transesophageal echocardiography (TEE) is a sensitive and specific procedure that gives detailed images of the thoracic aortic anatomy and blood flow; however, there are few reports on pitfalls with TEE. This case describes a patient with a typical history of a possible aortic rupture; artifacts in the TEE mimicked aortic rupture and development of a pseudoaneurysm. Echocardiographers should know this possible pitfall to make the correct diagnosis. PMID- 7986551 TI - A technique for performing transesophageal echocardiography safely in patients with Zenker's diverticulum. AB - Transesophageal echocardiography was indicated for evaluation of mitral valve pathology in a patient with a Zenker's diverticulum. However, transesophageal echocardiography is potentially dangerous and therefore relatively contraindicated in such patients. Our gastroenterologist directly intubated the esophagus with a fiberoptic endoscope and introduced an overtube through which transesophageal echocardiography was performed without incident. PMID- 7986553 TI - Doppler echocardiographic evaluation of severe rheumatic submitral valve stenosis. AB - The submitral apparatus may play a predominant role in rheumatic mitral stenosis and should be evaluated aggressively with Doppler echocardiography, especially in patients in whom percutaneous mitral balloon valvotomy is being considered. The following case presents a patient with rheumatic mitral valve stenosis in whom some noninvasive clues alerted us to the presence of predominant submitral stenosis. PMID- 7986554 TI - Left atrial metastasis from hepatocellular carcinoma: a case report. AB - This is the second reported case of a patient with hepatocellular carcinoma in whom the presence of a solitary, left atrial metastatic tumor was confirmed with the aid of transesophageal echocardiography. The tumor was discovered during computed tomography scanning at a follow-up examination after a 3-month regimen of chemotherapy. The patient had exhibited no signs of cardiac involvement, which may have been the result of the relatively small size of the tumor. Surgical excision of the tumor was successfully undertaken, and the patient's postoperative course was uneventful. In this case, transesophageal echocardiography was valuable in providing information regarding the exact location of the tumor and its relation to surrounding anatomical structures. PMID- 7986555 TI - Massive acute thrombosis of the descending thoracic aorta in heparin-associated thrombocytopenia and thrombosis. AB - Heparin-associated thrombocytopenia with thrombosis is a rare but serious complication in patients receiving heparin therapy. We report a case of a patient with this complication who had massive thrombosis within the descending thoracic aorta detected by transesophageal echocardiography. Our case suggests that a transesophageal echocardiographic examination can be useful in the early diagnosis of heparin-associated thrombocytopenia and thrombosis. PMID- 7986556 TI - Immediate postoperative recovery of regional wall motion after unilateral and bilateral internal mammary artery revascularization. AB - Within the last few years the importance of the internal mammary artery (IMA) for coronary revascularization has increased rapidly. Although there is no doubt about the superior long-term patency of this artery in comparison to saphenous vein grafts, the discussion about early postoperative results is controversial. The aim of the present study was to assess segmental wall motion after unilateral and bilateral IMA revascularization. Thirty-three patients who underwent elective myocardial revascularization were examined. In addition to vein grafts, bilateral IMA grafts were used in 8 patients and unilateral ones in 25 patients. Myocardial segmental wall motion was assessed by transesophageal echocardiography perioperatively. Myocardial protection was achieved by standard cold blood cardioplegia. Global left ventricular function remained unchanged postoperatively (4 h) in both groups (unilateral IMA: 52.8% +/- 7.1% vs 49.8% +/- 11.1%; bilateral IMA; 47.7% +/- 8.7% vs 48.7% +/- 7.7%, ns). Anterior wall motion (left IMA grafts to left anterior descending artery (LAD) was decreased early postoperatively (30 min) in both groups (unilateral IMA: 50.9% +/- 15.3% vs 37.8% +/- 14.5%; bilateral IMA: 47.3% +/- 20.1% vs 30.4% +/- 8.5%, P < 0.05). Posterior wall motion was decreased in the bilateral IMA group (right IMA to right coronary artery (RCA), 47.8% +/- 7.2% vs 28.0% +/- 8.9%, P < 0.05) and remained unchanged in the unilateral IMA patients (vein grafts to RCA, 39.5% +/- 9.9% vs 41.4% +/- 17.5%, ns). Internal mammary artery revascularization may result in deterioration of segmental myocardial function in the early (< 4 h) postoperative period. Bilateral IMA grafts should therefore be used with caution in patients with impaired ventricular function. PMID- 7986558 TI - Combined valve and coronary artery bypass surgery: early and late results. AB - Determinants of early, late and event-free survival of combined valve and coronary artery bypass graft (CABG) surgery were studied in 420 patients using multivariate analysis. It was found that the risk of hospital death increases 5 times when the preoperative NYHA class was > or = IV, 3 times when left ventricular (LV) function is significantly impaired and is double when mitral regurgitation is present. The survival probability of hospital survivors was 91% (87.3-94.5%) at 5 years. Late mortality was determined by advanced preoperative NYHA class ( > or = IV) and the presence of mitral regurgitation. The event-free survival probability of hospital survivors, i.e. total events including death, valve-related complications, ischemic complications and recurrent NYHA class > or = IV, was 73.0% (66.7-79.5%) at 5 years. Postoperative events were determined by the presence of preoperative NYHA class > or = IV, impaired ventricular function, mitral regurgitation and non-sinus rhythm. It is concluded that these parameters can be considered as the most important predictors of clinical outcome after combined valve and CABG surgery. PMID- 7986557 TI - Pre-operative aspirin decreases platelet aggregation and increases post-operative blood loss--a prospective, randomised, placebo controlled, double-blind clinical trial in 100 patients with chronic stable angina. AB - Aspirin has an established benefit in reducing the incidence of coronary events and vein graft occlusion. We have now assessed the risk of pre-operative aspirin in a prospective, randomised, double-blind clinical trial in 100 patients scheduled for elective coronary artery surgery. Any prescribed aspirin and non steroidal anti-inflammatory drugs were discontinued 2 weeks pre-operatively and these were replaced by a randomly assigned tablet of either aspirin 300 mg daily or placebo taken until the day of surgery. Patient compliance was confirmed by serum and urinary salicylate analysis. The two groups were similar in demographic characteristics, bypass time, number of grafts placed and number of internal mammary arteries used. All patients survived to be discharged home (see Table). Aspirin decreases platelet aggregation to arachidonic acid and to collagen both pre- and post-operatively. The benefit of pre-operative aspirin has to be balanced against the risk of increasing post-operative blood loss, re-exploration for excessive bleeding and transfusion requirements. PMID- 7986560 TI - Integrity and viability of homograft valves. AB - Since it has been suggested that the leaflet tissue viability influences durability after homologous valve replacement, we compared different harvest and preservation techniques in order to examine the quality and smoothness of homograft conservation. We analyzed human aortic and pulmonary valve leaflets obtained from 'heart-beating donors' (HBD) during heart transplantation and from 'non-heart-beating donors' (NHBD) during coroner's autopsies. Valves were either cryopreserved in liquid nitrogen or stored at 4 degrees C in nutrient medium similar to the procedure reported in our protocols of the homograft bank system. All grafts from NHBD had been antibiotically sterilized for 3 days beforehand. Morphological observations were made using light and electron microscopy and, in order to characterize the endothelial cell viability, a non-radioactive cell proliferation assay was used. The PGI2 secretion of the remaining endothelium was defined as the 6-keto-prostaglandin F1 alpha metabolite by an enzyme immunoassay. Observations in the scanning electron microscope revealed that, after cryopreservation, homografts show an almost confluent endothelium when processed within 24 h after harvest from HBD, but lack endothelial cells when obtained from NHBD. Cryopreserved grafts from NHBD exhibited an altered tissue structure with edema and vacuolization within the spongiosa of the leaflets as well as irreversible cell damage when examined under the light and transmission electron microscope. That the metabolic activity of HBD homografts was maintained was confirmed by proven PGI2 secretion (6150 +/- 1200 pg/3 ml M199 after cryopreservation), whereas specimens from NHBD showed a reduced (1950 +/- 730 pg/3 ml M199) and, after cryopreservation, almost no release (P < 0.0001).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7986559 TI - Prosthetic valve endocarditis: analysis of risk factors for mortality. AB - Between 1975 and 1990, 70 episodes of prosthetic valve endocarditis (PVE) were diagnosed in 65 patients at Leiden University Hospital. The overall mortality rate was 27%. Antecedent endocarditis attributable to the same micro-organism (mortality 63%, P = 0.02) and Staphylococcus aureus as the causative micro organism (mortality 100%, P = 0.001) were significant predictors for mortality. Sex, type and position of the valve and therapy had no significant influence on the mortality. All patients infected with S. aureus died, irrespective of whether they received medical treatment alone or in combination with surgery. None of the patients with streption, endocarditis had abscesses at reoperation; the mortality rate for this group was 14%. Abscess formation, especially in aortic valves, was the most important finding at reoperation and corresponded with a mortality rate of 55%. Ring abscesses occurred equally in patients with mechanical and bioprosthetic valves. Seven of the 15 patients (47%) with significant prosthetic valve dehiscence died. In patients with mitral valve endocarditis, localized dehiscence of the valve was observed. In conclusion a previous endocarditis attributable to the same micro-organism and the causative micro-organism (S. aureus) were important risk factors for mortality due to PVE. PMID- 7986561 TI - Video-assisted thoracic surgery: the approach of choice for selected diagnosis and therapy. AB - Unconvinced of the benefits of video-assisted thoracic surgery (VATS) over conventional posterolateral thoracotomy (PLT) we undertook an evaluation of the VATS approach for various diagnostic and therapeutic intrathoracic procedures. For the 18 months ending December 31, 1992, 55 consecutive patients (28 males, 27 females, age 48 +/- 17 years) were eligible to undergo VATS for diagnosis and/or treatment of a variety of conditions. Thirty-eight were chosen for VATS and 17 for PLT. Three VATS patients were converted to PLT (7.9%). Thus 35 VATS patients formed our first experience with the minimally invasive approach. We observed operating time (OT), length of stay (LOS), days of postoperative narcotic use (DNA), achievement of diagnostic and/or therapeutic objectives and morbidity and mortality. For analysis of LOS and DNA due to the procedure alone patients were outliers if LOS was prolonged for reasons other than the procedure, pain or related complications. For estimation of anticipated LOS and DNA due to VATS, 9 of the 35 VATS patients were outliers. For the remaining 26, LOS was 4.9 +/- 2.5 days and DNA was 2.6 +/- 1.7 days after surgery. For the 35 VATS patients OT was 87 +/- 30 minutes. Complications after VATS were few and similar to those experienced after PLT. A diagnostic and/or therapeutic objective was achieved in all patients without mortality. We found that definitive procedures carried out with VATS require fewer hospital days and less postoperative analgesia than expected after similar procedures performed through standard PLT. Diagnostic and therapeutic objectives are easily attainable and complications are few. (ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7986562 TI - Glucose-insulin-potassium (GIK) prevents derangement of myocardial metabolism in brain-dead pigs. AB - Brain death is associated with neuroendocrine changes resulting in reduced myocardial glycogen content. The purpose of this study was to investigate the effects of glucose-insulin-potassium (GIK), on myocardial metabolism in brain dead pigs. Sixteen brain-dead pigs were given GIK infusion (n = 8), or Ringer solution (n = 8). At end-point (7 h post brain death) arterial concentrations and myocardial arteriovenous (a-v) concentration differences of glucose, lactate and free fatty acids (FFA) were assessed, and myocardial biopsy specimens were taken from the right atrium and left ventricle. Biopsies were also taken from five normal pigs. Myocardial glycogen content in the GIK group was significantly higher compared to the control group, but comparable to the non-brain-dead animals. There was a higher and significant myocardial uptake of glucose and lactate in the GIK group compared to the controls. Plasma levels of FFA were significantly lower in the GIK group, and the myocardial uptake of FFA was 5 times higher in the control group compared to the GIK group. There were no significant differences in hemodynamic variables among the groups. In conclusion, intravenous supply of GIK to brain-dead pigs results in increased myocardial glycogen content and seems to prevent abnormal myocardial metabolism, which may have clinical implications for the myocardial protection of donor hearts. PMID- 7986563 TI - Aneurysmatic dilatation of an aortic homograft more than 30 years after implantation into the thoracic aorta. AB - A case of aneurysmatic dilatation of an aortic homograft 34 years after implantation for correction of a coarctation is presented. It was electively replaced by a Dacron prosthesis to prevent impending complications. PMID- 7986564 TI - Surgical repair of pseudo-aneurysm arising from a true chronic aneurysm of the left ventricular lateral wall. AB - Left ventricular aneurysm of the lateral wall is extremely rare. In our case it was followed by a complete rupture of the wall with formation of a pseudo aneurysm. This evolution of a chronic left ventricular aneurysm is only seldom described. PMID- 7986565 TI - Effect of high pressure on EcoRI reactions. AB - The effect of pressure on reactions of restriction endonucleases was investigated. No obvious irreversible (after) effect was observed for EcoRI, while a considerable irreversible inactivation was found for BamHI. Thus the EcoRI reactions against lambda DNA, pBR322 and pBluescript were studied under high pressure and little effect was observed on the overall reactions. The DNA concentration dependence of the kinetic data apparently fits the Michaelis-Menten type equation and the evaluated rate parameters were: Vmax = 6.2 +/- 0.24 and 7.0 +/- 0.22 (x 10(-2) nM/min) at 0.1 and 200 MPa, respectively; Km = 19 +/- 1.8 and 28 +/- 1.7 nM at 0.1 and 200 MPa, respectively. The apparent activation volume corresponding to kcat/Km was ca +1 mL/mol. A characteristic effect of pressure on the sequence specificity of these enzymes was seen in their star activity. Relaxed specificity was tightened by increasing pressure (200 MPa) with respect to that induced by low salt concentration or by the presence of organic solvent. PMID- 7986566 TI - Selective oxidation of methionyl residues in the human recombinant secretory leukocyte proteinase inhibitor. Effect on the inhibitor binding properties. AB - Binding of the human recombinant secretory leukocyte proteinase inhibitor (SLPI) [native and with the methionyl residues at positions 73, 82, 94 and 96 of domain 2 oxidized to the sulfoxide derivative (Met(O) SLPI)] to bovine alpha chymotrypsin (alpha-chymotrypsin) [native and with the Met192 residue converted to the sulfoxide derivative (Met(O) alpha-chymotrypsin)] as well as to native bovine beta-trypsin (beta-trypsin), which does not contain methionyl residues, has been investigated between pH 4.0 and 8.0, and between 10.0 degrees C and 30.0 degrees C, from thermodynamic and/or kinetic viewpoints. By increasing the number of oxidized methionyl residues present at the proteinase:inhibitor contact interface (from 0 to 3), the adducts investigated are increasingly destabilized and the relaxation time of the complexes into conformers less stable is enhanced. On the other hand, the selective oxidation of methionyl residues of SLPI and alpha-chymotrypsin, by reaction with chloramine T, does not affect the proteinase inhibition recognition mechanism. Therefore, even though conformational changes may occur in the conversion of native SLPI and native alpha-chymotrypsin to their Met(O) derivatives, a localized steric hindrance can be considered as the main structural determinant accounting for the reported results. PMID- 7986568 TI - Structural and physicochemical analysis of the reaction between the anti-lysozyme antibody D1.3 and the anti-idiotopic antibodies E225 and E5.2. AB - The reaction between the mouse (BALB/c) anti-idiotopic monoclonal antibodies E225 and E5.2 and idiotopes on the (BALB/c) anti-lysozyme monoclonal antibody D1.3 has been characterized by titration calorimetry, by equilibrium sedimentation and by the determination of binding association and dissociation rates. The reaction between E5.2 and D1.3 is driven by a large negative enthalpy and its rate and equilibrium association constants are comparable to those observed in other antigen-antibody reactions. In contrast, the reaction between E225 and D1.3 is entropically driven and characterized by slow association kinetics (1 x 10(3) M-1 sec-1) and a resulting low equilibrium constant (Ka = 2 x 10(5) M-1). A correlation of these properties with the three-dimensional structure of the Fab225-FabD1.3 complex, previously determined by X-ray diffraction methods to 2.5 A resolution, indicates that conformational changes of several D1.3 contacting residues, located in its complementarity determining regions, may explain these features of the reaction. PMID- 7986567 TI - Analysis of the interaction between human interleukin-5 and the soluble domain of its receptor using a surface plasmon resonance biosensor. AB - A surface plasmon resonance (SPR) biosensor was used to study the interaction of human interleukin-5 (hIL5) with its receptor. IL5 is a major growth factor in the production and activation of eosinophils. The receptor for IL5 is composed of two subunits, alpha and beta. The alpha subunit provides the specificity for IL5 and consists of an extracellular soluble domain, a single transmembrane region and a cytoplasmic tail. We expressed the soluble domain of the human IL5 receptor alpha subunit (shIL5R alpha) and human IL5 (hIL5) in Drosophila. Both hIL5 and shIL5R alpha were immobilized separately through amine groups onto the carboxylated dextran layer of sensor chips of the BIAcore (Pharmacia) SPR biosensor after N hydroxysuccinimide/carbodiimide activation of the chip surface. Interactions were measured for the complementary macromolecule, either shIL5R alpha or hIL5, in solution. Kinetics of binding of soluble analyte to immobilized ligand were measured and from this the association rate constant, dissociation rate constant and equilibrium dissociation constant (Kd) were derived. With immobilized shIL5R alpha and soluble hIL5, the measured Kd was 2 nM. A similar value was obtained by titration calorimetry. The Kd for Drosophila expressed receptor and IL5 is higher than the values reported for proteins expressed in different systems, likely due to differences in the methods of interaction analysis used or differences in protein glycosylation. Receptor-IL5 binding was relatively pH independent between pH 6.5 and 9.5. Outside this range, the dissociation rate increased with comparatively little increase in association rate.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7986569 TI - The making of the minibody: an engineered beta-protein for the display of conformationally constrained peptides. AB - Conformationally constraining selectable peptides onto a suitable scaffold that enables their conformation to be predicted or readily determined by experimental techniques would considerably boost the drug discovery process by reducing the gap between the discovery of a peptide lead and the design of a peptidomimetic with a more desirable pharmacological profile. With this in mind, we designed the minibody, a 61-residue beta-protein aimed at retaining some desirable features of immunoglobulin variable domains, such as tolerance to sequence variability in selected regions of the protein and predictability of the main chain conformation of the same regions, based on the 'canonical structures' model. To test the ability of the minibody scaffold to support functional sites we also designed a metal binding version of the protein by suitably choosing the sequences of its loops. The minibody was produced both by chemical synthesis and expression in E. coli and characterized by size exclusion chromatography, UV CD (circular dichroism) spectroscopy and metal binding activity. All our data supported the model, but a more detailed structural characterization of the molecule was impaired by its low solubility. We were able to overcome this problem both by further mutagenesis of the framework and by addition of a solubilizing motif. The minibody is being used to select constrained human IL-6 peptidic ligands from a library displayed on the surface of the f1 bacteriophage. PMID- 7986570 TI - Review of the safety assessment of polychlorinated biphenyls (PCBs) with particular reference to reproductive toxicity. AB - 1. The methods used to evaluate the toxicological effects of PCBs in animals have been reviewed. 2. The data show that Toxic Equivalency Factors (TEFs) could be developed to assess the potential toxicity of PCB mixtures for certain specific target organ effects (such as the liver and immune system) but would be inappropriate for other effects (e.g. thyroid function and neurochemical effects). More data on a wider range of individual PCB congeners and a method for systematically balancing toxicodynamic and toxicokinetic data are required before the TEF approach can be fully evaluated. 3. With the exception of the teratogenic effects seen in mice and the anti-oestrogenic effects reported in in vitro studies, there are insufficient data on individual PCB congeners to evaluate the structure-activity relationships for the effects of PCBs on reproduction. The data also show that individual PCBs may have opposing effects on a particular aspect of reproduction (for example individual PCB congeners may have either oestrogenic or anti-oestrogenic effects). Studies with individual PCB congeners have shown both enhancement and antagonism of the teratogenic effects of 2, 3, 7, 8-tetrachloro dibenzo-p-dioxin (TCDD) in the mouse. It is not possible to use TEFs to evaluate the reproductive effects of PCBs. 4. The mechanism(s) responsible for the effects of PCBs on postnatal neurobehavioural development in rodents and monkeys have not been elucidated. At least two groups of PCBs which might be responsible for the observed effects have been identified in this review, one affecting the dopaminergic system and the other group affecting thyroid hormone levels. Considerably more research would be required before the TEF approach could be applied to the effects of PCBs on postnatal neurobehavioural development. This would include research on an appropriate animal model to determine whether the critical toxicological mechanism is mediated through the Ah receptor. 5. The reproductive toxicity of complex PCB mixtures such as those found in foods will depend on the identifies and relative proportions of individual PCB congeners in the mixture. It is not possible to give an accurate estimate of a NOAEL or LOAEL from the reproduction studies using commercial PCB mixtures which could be readily applied to the safety assessment of PCBs present as contaminants in food. 6. It is concluded that the data presented in this paper support the hypothesis that there is no satisfactory method derived from the available studies in laboratory animals for evaluating the potential risk of adverse effects on reproduction posed by contamination of foods with PCBs. PMID- 7986571 TI - Elimination of antipyrine and its metabolites in interferon treated hepatitis C. AB - 1. To study the effect of interferon on hepatic drug metabolism in chronic hepatitis C, we examined nine patients before and at the end of 6 months of interferon treatment. 2. Routine liver function was determined together with the salivary clearance of antipyrine and the 48 h urinary excretion of the main metabolites of antipyrine: 4-hydroxyantipyrine, 3-hydroxymethylantipyrine and norantipyrine before and after 6 months of interferon treatment. 3. Liver pathology, routine liver function, and antipyrine metabolism remained unchanged after patients were treated for 6 months with interferon for a histologically advanced but clinically compensated chronic hepatitis C. PMID- 7986572 TI - Research on the baccalaureate completion process for RNs. PMID- 7986573 TI - Minorities in nursing. PMID- 7986574 TI - Native American health. PMID- 7986575 TI - Nursing research in Korea. PMID- 7986576 TI - Psychogenic pain in children. PMID- 7986577 TI - Fatigue during the childbearing period. PMID- 7986578 TI - Elder mistreatment. PMID- 7986579 TI - Rural health and health-seeking behaviors. PMID- 7986580 TI - Nursing workload measurement systems. PMID- 7986581 TI - Activation of HIV type 1 long terminal repeat by ultraviolet light is serum and strain specific. AB - We have studied the UV responsiveness of xeroderma pigmentosum (XP) and HeLa cell lines transfected with a CAT reporter gene under the control of the HIV-1 LTR promoter. XP fibroblasts grown in 10% newborn bovine serum (NBS) were three times more responsive to UV radiation than cells grown in 10% fetal calf serum (FCS). Moreover, cocultivation of UV-irradiated XP cells with XP cells containing stable integrants of HIV-LTR CAT was found to be more than four times more effective in inducing the CAT activity when cells were maintained in 10% NBS than in 10% FCS. The level of induction was also dependent on the serum concentration. These data indicate that a serum component, possibly a cytokine(s), can enhance the UV response of both irradiated cells and unirradiated cells cocultivated with irradiated cells. The magnitude of UV responsiveness seemed also to be strain dependent. CAT activity for the HIV LTR promoter from the HTLV-IIIB (HIV-IIIB) strain was induced more than 30-fold by UV irradiation whereas activity from the LAV-1BRU strain was less than 2-fold. In contrast, both constructs were strongly induced by Tat expression. This indicates that there are differences in the induction mechanism for these two stimuli, even though UV radiation has been previously reported to induce a cellular Tat-like factor (Valerie K, et al., Nature [London] 1988;333:78-81). PMID- 7986582 TI - Stimulation of human immunodeficiency virus type 1 expression by ceramide. AB - Ceramide, an intracellular lipid mediator of tumor necrosis factor alpha (TNF alpha) action, was studied for its effects on the expression of the proviral human immunodeficiency virus type 1 genome in latently infected myelomonocytic cell lines U-1IIIB and OM-10.1. Ceramide treatment resulted in a 20- to 100-fold enhancement of HIV production in these cells. Ceramide also enhanced the expression of the chloramphenicol acetyltransferase gene directed by a human immunodeficiency virus type 1 long terminal repeat in transfected U-937 cells, indicating that ceramide acts at the level of viral transcription. These observations suggest that the TNF-ceramide signaling system may be involved in the regulation of HIV expression in certain myeloid cell types. PMID- 7986583 TI - HIV type 1 Tat protein induces immunoglobulin and interleukin 6 synthesis by uninfected peripheral blood mononuclear cells. AB - Tat is a potent trans-activating protein encoded by the HIV genome. It is essential for viral replication, but has pleiotropic effects on host cells as well. We demonstrated that exogenous recombinant Tat increases immunoglobulin (Ig) and interleukin 6 (IL-6) production in vitro by normal uninfected peripheral blood mononuclear cells by 100-500%. The optimal Tat concentration was 100 ng/ml, but even a low concentration of 1 ng/ml induced a response in most subjects. The observed induction was inhibited by monoclonal anti-Tat antibodies and 2,3 dimercapto-1-propanol. Both anti-IL-6 antibodies and IL-6 antisense oligonucleotides inhibited Tat-induced IgG and IgA synthesis to some degree, whereas induction of IgM appeared to be independent of IL-6. We conclude that Tat can function in vitro in the absence of any other viral structures and induce Ig and IL-6 production; the clinical significance of these findings remains as yet undetermined. PMID- 7986584 TI - Anti-HIV type 1 properties of chemically modified heparins with diminished anticoagulant activity. AB - Several groups have reported that sulfated polysaccharides are potent and selective in vitro inhibitors of human immunodeficiency virus type 1 (HIV-1); however, their therapeutic application is limited by their anticoagulant activity. In view of possible improvements in therapeutic potential, a number of heparin derivatives with reduced anticoagulant activity were studied for their inhibitory activity of an HIV-dependent syncytium formation assay, in comparison with standard anionic polysaccharides, such as sodium heparin, dextran sulfate, and heparin sulfate. The chemical modifications introduced in the heparin molecule included succinylation of desulfated N groups (Suc-H), exhaustive periodate oxidation and reduction (RO-H), and controlled nitrous acid degradation (LMW-H). The most pronounced anti-HIV activity was observed with RO-H, Suc30-H (standard heparin, 30% succinylated), and Suc100-LMW-H (low molecular weight heparin, 100% succinylated); the latter retained only 5% of the anticoagulant activity of standard heparin, whereas RO-H and Suc30-H retained approximately 35% of the anticoagulant activity of standard heparin. A safety ratio (arbitrary units of anti-HIV activity per anticoagulant international unit) was calculated: by this parameter, RO-H, Suc30-H, and Suc100-LMW-H were, respectively, 48-, 3.6-, and 1644-fold more safe than standard heparin. PMID- 7986585 TI - Interleukin 13 and interleukin 4 protect bronchoalveolar macrophages from productive infection with human immunodeficiency virus type 1. AB - In this study, we examined the impact of the predominantly Th2-type lymphokines interleukin 13 (IL-13) and interleukin 4 (IL-4) on acute infection of human bronchoalveolar macrophages with a macrophage-tropic isolate of human immunodeficiency virus type 1 (HIV-1). Addition of 0.01-10 ng of IL-4 or IL-13 per milliliters significantly blocked HIV-1 replication in infected cells, judging from levels of reverse transcriptase and p24 antigen in the supernatants of infected cells. Both IL-4 and IL-13 were almost as efficient as interferon gamma (IFN-gamma) in preventing HIV-1 replication, when given in equivalent amounts. Moreover, neither IL-13 nor IL-4 interfered with the IFN-gamma-mediated enhancement of anti-HIV-1 activity in alveolar macrophages. Both IL-4 and IL-13 interfered with enhanced replication of HIV-1 in macrophages pulsed with the growth factor granulocyte-macrophage colony-stimulating factor (GM-CSF). Interleukin 13 also prevented HIV-1 release from peripheral blood mononuclear cells in a cocultivation experiment with feeder cells from a seronegative subject. These data suggest that Th2-derived lymphokines have significant anti HIV-1 activity in cells of the macrophage lineage, although they may enhance the susceptibility of HIV-1-infected subjects to some opportunistic pathogens. PMID- 7986586 TI - HIV type 1 infection of CD4+ T cells depends critically on basic amino acid residues in the V3 domain of envelope glycoprotein 120. AB - The third variable domain (V3 domain) of the human immunodeficiency virus type 1 (HIV-1) envelope glycoprotein gp120 is a major determinant of phenotypic variability. The V3 domain of HIV-1 has many basic amino acid residues. Lymphocytotropic HIV-1 tends to have a V3 domain with a higher density of positive charge than does monocytotropic HIV-1. The importance of basic residues in the V3 domain for the HIV-1 infectivity, however, has not been well investigated. Here we show that mutation of basic amino acid residues at positions 303, 306, 309, 313, and 325 in the V3 domain of the lymphocytotropic isolate NL4-3 results in a dramatic elimination of both virus infectivity and syncytium-inducing ability. Three basic amino acid substitutions (at position 306, 309, and 313) induced a decrease in the binding ability of two kinds of neutralizing antibodies (NEA9284 and 0.5 beta) that recognize a different site in the V3 domain. This suggests that the basic residues play an important role in maintaining the tertiary structure of the V3 domain. Monocytotropism was not simply dependent on either decreased positive charge in the V3 domain of NL4-3 or on mutation of lysine to glutamate at position 320, which is a characteristic amino acid of monocytotropic HIV-1. These findings contribute to our understanding of the significance of basic residues on the function of envelope glycoprotein. PMID- 7986587 TI - Contrasting IgA and IgG neutralization capacities and responses to HIV type 1 gp120 V3 loop in HIV-infected individuals. AB - Quantitative analysis for HIV-1-specific antibodies present in IgA and IgG preparations purified from the serum of HIV-seropositive individuals indicated that the proportion of HIV-specific antibodies present within the IgG isotype was seven times greater than the proportion of IgA HIV antibodies present within the IgA isotype. Dilution of IgA HIV-specific antibodies by nonspecific IgA was observed in patients with elevated serum IgA concentrations, whereas proportions of IgG HIV antibodies rose with increases in concentrations of serum IgG. Although proportions of IgA HIV antibodies were not observed to correlate with the CD4 counts of the individuals from whom immunoglobulins were purified, a significant association between the numbers of such cells and proportion of HIV antibodies present in the IgG isotype was found. Equivalent amounts of IgG were also more effective than IgA at inhibiting HIV-1IIIB infection of a susceptible T cell line. This may be due to the presence of higher proportions of IgG antibodies directed toward non-V3 determinants because reactivity against an HIV 1IIIB V3 peptide was low and did not differ significantly between these isotopes. IgA antibodies reacting against a V3 peptide containing the HIV consensus sequence could be detected in the majority of IgA samples purified from infected individuals. Proportions of IgG consensus V3-specific antibodies within the purified IgG samples were, however, much higher. The presence of accompanying increases in serum IgG concentration and proportions of IgG HIV antibodies, higher proportions of both HIV- and consensus V3-specific antibodies within this isotype, and more effective neutralization by IgG suggests that an HIV-driven response is dominated by B cells committed to production of this immunoglobulin isotype. The observed low proportions of HIV antigen-specific IgA antibodies with dilution in many individuals by elevations in non-HIV-specific IgA suggests that IgA B cells may be more susceptible to factors that mediate the polyclonal activation believed to be responsible for many of the B cell disorders characteristic of HIV infection. PMID- 7986588 TI - Panel of anti-gp120 monoclonal antibodies reacts with same nuclear proteins in uninfected cells as those recognized by autoantibodies from patients with systemic lupus erythematosus. AB - Mouse monoclonal antibodies (MAbs) directed against the HIV-1 gp120 envelope protein were screened for their reactivity with intracellular antigens expressed in normal uninfected monocytes by indirect immunofluorescence and immunoblotting. Some of these MAbs reacted with the nuclei of normal uninfected cells, producing three main staining patterns by indirect immunofluorescence. Western blot analysis showed that these monoclonal antibodies recognize peptides of various molecular weights present in nuclei preparations of normal monocytes. Reactivity with peptides of similar molecular weight was also detected in sera from both HIV infected individuals and patients with systemic lupus erythematosus. This evidence for antigenic similarities between HIV-1 gp120 and nuclear antigens represents a novel example of molecular mimicry of self-antigens by HIV envelope proteins, which supports the involvement of mechanisms of autoimmunity in HIV disease pathogenesis through recruitment of autoimmune responses to self structures by HIV antigens. PMID- 7986589 TI - High-titer immune responses elicited by recombinant vaccinia virus priming and particle boosting are ineffective in preventing virulent SIV infection. AB - Eighteen rhesus monkeys were vaccinated with recombinant vaccinia viruses expressing SIVmac antigens in 3 separate rounds of experiments. Twelve of the monkeys were primed with a trivalent vaccinia virus recombinant expressing Gag, Pol, and Env polypeptides that can assemble into SIV pseudovirion particles and boosted with SIV particles in adjuvant. Four of the monkeys were primed with different vaccinia virus recombinants expressing env or gag+env followed by SIV particle boosts; two received vaccinia virus recombinants alone (env or env+gag). Despite the induction of vigorous immune responses, 17 of 18 rhesus monkeys became infected on challenge with a low dose of virulent SIVmac. The single protected animal was one of three challenged with homologous cloned SIV exactly matched to the clone used for construction of trivalent vaccinia virus recombinant and particles. Vaccination may have diminished SIV burdens and rates of CD4+ cell declines in some of the animals, but vaccinated/challenge/infected animals eventually developed fatal disease similar to control animals. These results highlight the extreme difficulty in achieving vaccine protection against virulent SIVmac infection even under idealized laboratory conditions. PMID- 7986590 TI - Induction of antigen-specific killer T lymphocyte responses using subunit SIVmac251 gag and env vaccines containing QS-21 saponin adjuvant. AB - Subunit vaccines based on recombinant proteins have proved useful for inducing antibody responses and they are safe for widespread use because they do not contain any live components. Unfortunately, they do not typically induce the types of cell-mediated immune responses required to control viral pathogens; specifically, they do not induce CD8+ cytotoxic T lymphocyte (CTL) responses. To increase the immunogenicity of recombinant proteins, we have used the QS-21 saponin adjuvant in subunit vaccine formulations. In the current study, experimental subunit vaccine formulations containing recombinant p55gag or gp120env proteins from the mac251 strain of the simian immunodeficiency virus (SIVmac251) and the QS-21 adjuvant were used to immunize rhesus macaques. These formulations induced SIV gag- or env-specific cellular immunity that was detectable in vitro and included killer cell activity. The induction of killer cells required prior vaccination and the responses were antigen specific for the immunogens contained in the vaccine formulations. Autologous target cells were required to detect these responses, suggesting genetic restriction, and effector cells appeared to be present in both the CD4+ and CD8+ T lymphocyte subpopulations. These data suggest that the vaccine-induced killer cell activity that was detected was mediated by both CD4+ and CD8+ lymphocytes. Despite the presence of these killer cells, all of the animals became infected with the SIVmac251 on experimental challenge. These findings demonstrated that antigen specific killer cell responses could be induced by a subunit vaccine formulated with the QS-21 saponin adjuvant. The characteristics of the responses suggested that the effector cells were T lymphocytes, expressing either CD4 or CD8.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7986591 TI - Immunological and virological changes associated with decline in CD4/CD8 ratios in lymphoid organs of SIV-infected macaques. AB - The decline in CD4/CD8 ratios in lymph nodes (LNs) of SIV macaques and HIV infected individuals occurs later than that in blood. In a previous study, long term SIV-infected macaques were delineated into two groups: (1) those whose LNs had normal CD4/CD8 ratios and (2) those whose LNs had low CD4/CD8 ratios. In the present investigation, LNs, spleens, and blood from these groups have been further analyzed to ascertain the cellular and virological events, particularly those involving CD8+ cells, that occur concomitantly with LN CD4% decline. An increase in the percent of CD69-, IL-2R(p75)-, CD45RA1o CD8+ cells was the most constant event observed in lymphoid tissue from mid- to late-stage SIV-infected monkeys. Such cells were sometimes observed in LNs prior to any other immunological or morphological changes. However, decline in LN CD4/CD8 ratios and the associated degeneration of follicular dendritic cells (FDCs) in the germinal centers (GCs) of these nodes were observed only when both CD8+ cell infiltration of GCs and accumulation of viral antigens within the FDC network could be demonstrated. These dramatic changes were also associated with significantly reduced responsiveness to mitogens throughout the lymphoid compartment. In terms of viral burden, immunological and structural collapse of LNs was not always associated with increased viral DNA levels. Despite the CD4+ cell decline in blood during HIV and SIV infections, the immunological and architectural collapse of the lymphoid compartment, which comprises the bulk of the lymphocytes in the body, appears to be a critical event leading to the onset of AIDS. The present findings suggest that increased CD8+ cell activity as well as decrease in CD4+ cell function both contribute to this process. PMID- 7986593 TI - Genetic and phylogenetic analysis of env subtypes G and H in central Africa. PMID- 7986592 TI - HIV type 1 envelope sequence diversity in inner city community. PMID- 7986594 TI - [The treatment of upper digestive hemorrhage of peptic origin: intravenous ranitidine versus intravenous omeprazole]. AB - OBJECT: To evaluate the effectiveness of Ranitidine i.v. versus Omeprazole i.v. for gastrointestinal bleeding of peptic origin. MATERIAL AND METHODS: Prospective, comparative, randomized and open study of 81 in-patients, hospitalized consecutively during 13 months, with gastrointestinal bleeding of peptic origin and signs of recent hemostasis (S.R.H.), belonging to the groups Forrest Ib and II. Treatment groups: group A: Ranitidine: initial injection of 50 mg. i.v., followed by 100 mg/6 hours i.v., during the first 72 hours and afterwards by 150 mg/12 hours, orally; group B: Omeprazole: initial injection of 80 mg. i.v., followed by 40 mg/8 hours i.v. during the first 72 hours and afterwards by 20 mg/24 hours, orally. Evaluation criteria: persistent haematemesis and melena; need for transfusions: treatment failure average period of hospitalization and disappearance of S.R.H. after 72 hours. RESULTS: 43 patients received Ranitidine and 38 Omeprazole. Both groups were homogeneous in regard to variables ar hospitalization. No significant differences were found between these two groups: persistent melena (26% group A vs. 8% group B); patients who needed transfusion (39% vs. 31%); treatment failure (19% vs. 5%); average period of hospitalization; and disappearance of S.R.H. (81% vs. 95%). None of the patients died. CONCLUSIONS: The effectiveness of Ranitidine i.v. and Omeprazole i.v., in the dosage used and in a selected group of patients with gastrointestinal bleeding, is similar. However, there is a trend to register less treatment failures and a higher percentage of S.R.H. disappearance with the patients treated with Omeprazole. Further studies with more patients are necessary to confirm this tendency. PMID- 7986595 TI - [The effect of environmental factors in inflammatory bowel disease]. AB - In an attempt to elicit risk factors in inflammatory bowel disease in Spain, we have carried out a case-control study in which we conducted personal interviews asking marital status, place of residence, economic status, use of tobacco and contraceptives, and the method of lactation in infancy. IBD was more common in patients with a low economic level; UC was predominantly found in rural population. No differences were found in the remaining categories. Our results differ from those reported from North and Central Europe. PMID- 7986596 TI - [The morphometric changes of chronic ischemia in the hepatocyte. An experimental study in the rat]. AB - The effects of chronic ischemia on the rat hepatocyte are morphometrically analyzed in the present study. Rats Wistar-Lewis are used. Rats underwent a stenosis of the celiac artery by using a metallic guide. The interval between the experimentation until the sacrifice was 15, 30, 90, 180, and 360 days. We have performed a morphometric study using a semiautomated image analyzer system (VIDS III, Analytical Measuring Systems). Morphological disturbances in the chronic ischemia periods above mentioned can be measured: an increase in the hepatocyte area starting from 90 days of experimentation and also an increase in the hepatocyte perimeter starting from 30 days of ischemia. On the other hand, both the nuclear area and the nuclear perimeter are increased in every period studied. The number of hepatocytes per microscopic field doesn't show any change in relation to ischemia time. Cellular swelling suggests some degree of cellular hypoxia in contradiction with other observations. PMID- 7986597 TI - [The correlation of the isotopic liver/spleen ratio with the tissue damage in chronic diffuse hepatopathies]. AB - The purpose of the study was to determine whether a correlation between the radioisotopic "spleen-to-liver" ratio and the hepatic damage (according to Knodell's Index) exists in patients with chronic liver disease, in order to ascertain whether hepatic biopsy should be performed under visual (laparoscopic) control or not (blind liver biopsy). Thirty patients with inflammatory chronic hepatic disease were studied (9 chronic persistent hepatitis, 14 active chronic hepatitis and 7 hepatic cirrhosis). An inverse correlation was found between Knodell's Index and the "spleen-to-liver" ratio with moderate statistical significance (r = -0.46). In conclusion, the isotopic "spleen-to-liver" ratio correlates moderately well with the degree of hepatic damage and consequently it can only be used as orientation about the preferable way for obtaining a liver biopsy (laparoscopically or not). PMID- 7986598 TI - [The usefulness of abdominal echography in the diagnosis of portal hypertension in cirrhotic patients]. AB - The differences in sonographic measurements of the splanchnic vessels, their modifications during respiration, the spleen size and the presence of collaterals of the portal system among 110 cirrhotic patients with portal hypertension and 30 control subjects are analyzed to verify the usefulness of conventional sonography in the diagnosis of portal hypertension. We achieved a sensitivity above 70% and a specificity of at least 90% with the following signs: 1) dilation of portal, splenic and superior mesenteric veins, 2) limited variations of the latter two during respiration, and 3) splenomegaly. A higher sensitivity was achieved considering variations in splenic caliber during respiration under 33% (91%) or superior mesenteric vein during forced expiration above or equal than 7 mm (88%). These measurements could be found in 71.8% and 57.2% respectively. On the other hand, values of portal vein and spleen size were easily obtained. The usefulness of all measurements persists if we take into account only patients with Child Pugh score < 7. Collateral circulation was demonstrated in 18%. Portal vein above 14 mm, variations in splenic caliber under 13% or superior mesenteric vein during forced expiration above or equal than 9 mm were obtained in any of control subjects but respectively in 33%, 46% and 69% of patients in portal hypertension group. We conclude that ultrasonography is a reliable and noninvasive tool in the diagnosis of portal hypertension in cirrhotic patients. PMID- 7986599 TI - [The results of duodenopancreatectomy in periampullar pathology]. AB - OBJECTIVE: To examine mortality and morbidity rates after pancreaticoduodenectomy in 69 consecutive patients with periampullar disease operated on between 1985 and 1993 at the Reina Sofia Hospital, Cordoba, Spain. PATIENTS: Fifty five patients (79.7%) had malignant neoplasm whereas 14 (20.3%) had benign disease. In 58 patients a Whipple procedure was performed; pancreaticoduodenectomy with preservation of the pylorus (Traverso-Longmire) was performed in the remaining 11 patients. RESULTS: Eighteen patients (26%) had postoperative complications; peritoneal bleeding (1); biliary fistula (3); pancreatic fistula (4); digestive fistula (2); and pancreatitis (2). Two patients with pancreatic and duodenal carcinoma died. Thirteen patients were readmitted: 3 bleeding episodes in anastomotic ulcer; 3 hepaticojejunostomy obstruction; and the remaining 6 patients with tumor recurrence. CONCLUSIONS: In our experience duodenopancreatectomy was a safe procedure in periampullar disease, with an acceptable morbidity and mortality rates. PMID- 7986600 TI - [The epidemiology and etiology of hepatocarcinoma]. AB - Hepatocellular carcinoma is the most frequent hepatic primary neoplasm. Its geographic distribution is inhomogeneous, with high, medium and low zones of incidence. The role of etiologic factors such as aflatoxin exposure. Hepatitis B virus, hepatitis C virus, ethanol, liver cirrhosis and sex hormones is discussed. PMID- 7986601 TI - [Adult patients with clinically suspected or known biliopancreatic pathology in whom ERCP is not indicated: the 10 most frequent situations]. AB - Endoscopic retrograde cholangiopancreatography is an invasive endoscopic technique widely used in the diagnosis and eventual therapeutic procedures of many biliopancreatic conditions. While endoscopic retrograde cholangiopancreatography indications are well known, it is not the same in those patients with clinically suspected or known biliopancreatic entities in whom endoscopic retrograde cholangio-pancreatography is not indicated because it will not add valuable information with the potential of changing the previous diagnosis or therapy. Ten very common clinical situations in which this technique is not indicated are presented; among them idiopathic abdominal pain, some pancreatic carcinomas, chronic pancreatitis and pancreatic pseudocyst, and some patients awaiting conventional or laparoscopic cholecystectomy. We acknowledge that some aspects of this paper are controversial. PMID- 7986602 TI - [A patient with gastrointestinal manifestations and the common variable immunodeficiency syndrome]. AB - A case of 26-year-old male patient is presented. He developed a "sprue-like" syndrome, giardiasis and nodular lymphoid hyperplasia of the gastrointestinal tract. After the immunological study, the common variable immunodeficiency diagnosis was established. Pathogenic and diagnosis aspects were analyzed. Therapeutic response was excellent. PMID- 7986603 TI - [Volvulus of the transverse colon: a rare cause of intestinal obstruction]. AB - Volvulus of the transverse colon is rare, given its short and fixed mesentery and the normal fixation of the hepatic and splenic flexures of the colon. The case reported herein brings the total of reported cases to 72. Various predisposing factors have been identified, most notably congenital abnormalities, physiologic disturbances and mechanical obstruction; in our case these three factors were present. The possible role of colonoscopy in diagnosis and/or therapy is unclear. In our patient, colonoscopy proved to be of no use for diagnosis or treatment. PMID- 7986604 TI - [Pseudotumoral hepatic tuberculosis]. AB - In the absence of active pulmonary disease, hepatic focal tuberculosis is a rare form of tuberculosis. We present a case of pseudotumoral hepatic tuberculosis in a 44-year-old man; diagnosis is difficult because of its radiological similarity with primary or metastatic hepatic cancer. Percutaneous biopsy with US or CT guidance offers a good diagnostic alternative to laparoscopy. Histology examination revealed a tuberculoid granulomatous lesion. The disease has a good response to tuberculostatic treatment. PMID- 7986605 TI - [Ascitic peritonitis due to Candida albicans]. AB - We report a case of spontaneous peritonitis due to Candida albicans, in a diabetic patient with alcoholic liver cirrhosis, ascites, gastrointestinal bleeding from esophageal varices, sepsis, renal failure and encephalopathy. These factors, added to prolonged antibiotic therapy and instrumental manipulations, could have resulted in the colonization by Candida, usually described in secondary peritonitis, but perhaps underdiagnosed in cirrhotic patients with spontaneous peritonitis and severe multiorgan failure. PMID- 7986606 TI - [Pancreatic endocrine F-cell tumor]. AB - Two cases of pancreatic F-cell malignant tumors, producing only pancreatic polypeptide (PP) with clinical, biochemical and immunohistochemical features are described. No PP-associated endocrine symptoms were present. In both tumors, definitive diagnosis was immunohistochemical, and surgical treatment was carried out. Clinical evolution in the two patients was different: one of them died within the postoperative period with upper gastrointestinal bleeding by multiple duodenal ulcers, whereas the other--with lymph node metastasis at intraoperative diagnosis--is alive six years after treatment. F-cell tumors can be classified among the group of silent endocrine tumors of the pancreas. The reason for their discrepancy in the clinical behavior is unknown. PMID- 7986607 TI - [Pancreas divisum and acute pancreatitis]. PMID- 7986608 TI - [Does pregnancy influence the activity of chronic hepatitis C?]. PMID- 7986609 TI - [Intestinal malrotation in an adult]. PMID- 7986610 TI - [Blood gastrin changes in the late postoperative period after proximal gastric vagotomy]. AB - Changes in serum gastrin levels in the late postoperative period have been studied in 24 patients with non-stenotic duodenal ulcer who underwent proximal gastric vagotomy. Twenty healthy volunteers were used as a control group. Serum gastrin levels were determined under basal conditions and after a high protein meal stimulation. Both measurements were done in the preoperative, early postoperative (12th day) and late postoperative periods (X = 5.5 yrs.). Regarding basal serum gastrin levels, the results show mean values of 46.2 pg/ml in the preoperative, 61.6 pg/ml in the early postoperative, 73.9 pg/ml in the late postoperative and 51 pg/ml in the control group. Early and late postoperative period values show statistical significant differences when compared with preoperative values (p < 0.05), but not with the control group ones. Stimulated gastrin levels show mean values of 75.7 pg/ml in the preoperative, 99.1 pg/ml in the early postoperative, 134.1 pg/ml in the late postoperative and 73.4 pg/ml in the control group. Late postoperative values show statistical significant differences when compared with preoperative and early postoperative values (p < 0.05), and also when compared with the control group (p < 0.05). Possible causes and the physiopathological effects of these variations are discussed. PMID- 7986611 TI - [Nonelective colorectal surgery. Does age determine the results?]. AB - OBJECTIVE: To evaluate the influence of age on the morbi-mortality after non elective colorectal surgery. DESIGN: Retrospective analysis. SUBJECTS: 150 consecutive patients who underwent non-elective colorectal surgery between 1986 and 1992 [65 patients aged under 70 years (Group I)] and 85 patients aged 70 years or over (Group II)]. RESULTS: Using multiple regression analysis we have found: 1) Mortality is determined by the presence of associated risk factors (p < 0.001 tv = 4.11), the presence of peritonitis (p < 0.05 tv = 2.08) and by the admission-operation interval (p < 0.05 tv = 2.10). 2) Overall morbidity increases with age (p < 0.01, tv = 3.22) and the benign nature of the colorectal disease (p < 0.05, tv = 2.00). CONCLUSION: Age does not influence mortality in non-elective colorectal surgery even though it is a determinant risk factor in morbidity increase. PMID- 7986612 TI - [Cytomegalovirus enteritis and colitis in nonimmunodepressed patients, a primary disease or superinfection?]. AB - Cytomegalovirus disease is an opportunistic infection that is seen in patients with inmunodeficiencies. The group most commonly affected are AIDS and transplanted patients. Only a few cases of cytomegalovirus disease in non immunocompromised patients have been reported. In localized disease, the gastrointestinal tract is the most frequently affected. We report two cases of acute abdomen caused by cytomegalovirus enteritis and colitis (histopathological diagnosis) without any underlying immune disorder. The role that the cytomegalovirus infection might play in the development of the clinical manifestations in these two cases is discussed. Without an established immunodeficiency we must be careful to attribute to cytomegalovirus infection the direct responsibility of the lesions. In the reported cases, the existence of intestinal ischemia is more than just a clinical hypothesis and pathological examination is inconclusive. The absence of an immunocompromised state, the presentation as an acute abdomen and the clinical course forwards intestinal occlusion in the first case are not characteristic of cytomegalovirus enteritis and colitis. We conclude that the two reported cases are in fact an ischemic enteritis upon which cytomegalovirus enteritis and colitis was superimposed, an association that has not been reported before. PMID- 7986613 TI - [Colostomy closure: is it an intervention without risk?]. AB - OBJECTIVE: To examine whether colostomy closure is an operation with a high risk of complications. DESIGN: Retrospective study of colostomy closures in a 14-year period. PARTICIPANTS: 60 patients, averaging 54 years, males in 63%. The main indication for colostomy was colorectal neoplasm (47%), followed by trauma (23%). RESULTS: There were 15 Hartman's procedure reconstructions, 4 reconstructions of colostomy and mucous fistula, and 41 "simple" colostomy closures. The closure was extraperitoneal in 40%, suturing only the anterior colonic wall in 42%. We had 27 postoperative complications in 33% of the patients, without mortality. The average hospital stay was 8 days longer in the group with complications. The complication rate was 29% in the "simple" closure versus 42% in the reconstruction group (this difference was not statistically significant). The statistic analysis (chi-square and Mann-Whitney tests) showed no influence on morbidity of factors such as age, sex, previous disease, age of colostomy, and type and closure technique of colostomy. CONCLUSIONS: Colostomy closure has a high rate of postoperative complications (33%). These are minor in almost all cases, without mortality. PMID- 7986614 TI - [The endoscopic management of postoperative biliary fistulae]. AB - We report a series of 15 patients with a postoperative biliary fistula treated by endoscopic sphincterotomy. The exact location of the bile leak was revealed by ERCP in 13 cases (87%): cystic duct remnant in 6 (39%), intrahepatic biliary tree in 4 (26%), and main bile duct in 3 (20%). In all cases a distal obstacle (ie: retained stones, hydatid material) to bile flow was also found in ERCP. Treatment consisted of endoscopic sphincterotomy and subsequent removal of the distal obstacle, and could be completed in 13 (87%) cases. In our experience the treatment of postoperative biliary fistula with a distal obstruction bile flow by endoscopic sphincterotomy is a safe and effective procedure, and should be recommended as the first option in those patients. PMID- 7986615 TI - [Splenic cysts]. PMID- 7986616 TI - [H. pylori and gastroduodenal pathology in 1994. A change of medical attitude to peptic ulcer]. PMID- 7986617 TI - [Adenosquamous carcinoma of the stomach]. AB - Adenosquamous carcinoma (ASC) of the stomach is a rare tumour. In this report we present a case of adenosquamous carcinoma in the antrum involving the duodenal bulb in a 84 year old woman. Although several theories about the possible origin of this kind of tumours had been proposed, histological and immunohistochemical findings agree with the possibility of a preexisting adenocarcinoma as the most reliable cause. The prognosis of ASC seems worse than that of adenocarcinoma because of the more extensive tumour depth and higher frequency of lymphatic and vascular permeation of the carcinomas cells when it is discovered. PMID- 7986618 TI - [Ulcerative jejunitis: a complication of celiac disease]. AB - We report the case of a 57-year-old woman with celiac disease of long standing, who developed episodes of intestinal obstruction during two months. They were misdiagnosed as intestinal obstructions caused by adhesions. The barium meal and follow-through examination disclosed several jejunal stenoses. Therefore, the patient underwent early surgery where an intestinal resection was carried out. The histological examination showed the presence of benign ulcers at the stenoses. After surgery, the patient began to gain weight and her nutritional state improved remarkably. PMID- 7986619 TI - [Intestinal cystic lymphangiomas]. AB - Lymphangiomas are benign tumors of the lymphatic system. Their abdominal location is infrequent. We report two cases, one in the first jejunal loop and the other one in the mesentery. The latter was removed by laparoscopic surgery, technique that allows a wider resection. PMID- 7986620 TI - [Iatrogenic perforation of the intrathoracic colon after a late traumatic diaphragmatic hernia]. AB - A case of delayed presentation of traumatic diaphragmatic hernia and colonic injury leading to a review of the literature. Relative diagnostic difficulty in this type of lesions and its acute presentation make managements by mistake, as this one. In a patient with very important acute respiratory embarrassment and chest pain, an Argyle tube was placed because pneumothorax was suspected; the patient improved, but a fluid bowel content was obtained through the drainage tube; TAC and barium enema film showed the colon into the thorax. The patient underwent thoracotomy and laparotomy. In her history, she suffered from a stab wound on the left abdominal flank four years ago; it did not require surgical treatment but it caused the start of the colon movement into the thorax. The ways of presentation and its development are reviewed with the aim of remembering that it must be borne in mind if a patient present a penetrating trauma in the lower chest or upper abdomen, especially if surgical operation was not required, as it happened in this case. A careful history, examination, and review of follow up chest X-ray appears to be the easiest mechanism to avoid delays in diagnosis and reduce the morbi-mortality of this important disease. PMID- 7986621 TI - [An adenocarcinoid tumor of the vermiform appendix]. AB - Goblet cell carcinoids of the vermiform appendix are uncommon. A comprehensive review of the literature revealed about 100 reported cases. Clinical presentation included: asymptomatic patients, acute appendicitis, and/or chronic intermittent lower abdominal pain with or without a palpable mass. We report the case of a 57 year-old woman with lower abdominal pain, nausea and vomiting. Normal blood tests. X-ray of the abdomen showed dilated small bowel loops with fluid levels. Initially, conservative treatment was started. After three days with no clinical improvement, the patient was operated on. An appendicocecal inflammation was found and a terminal ileum plus cecal resection with an end-to-side anastomosis was performed. The pathological diagnosis was goblet cell carcinoid. The patient shows no evidence of recurrence after 1 year follow-up. PMID- 7986622 TI - [Malignant schwannoma with an atypical location]. PMID- 7986623 TI - [Cancer of the gallbladder. A case with cholestasis due to a rare mechanism]. PMID- 7986624 TI - [Congenital hypertrophy of the retinal pigment epithelium]. PMID- 7986625 TI - [A pancreatic abscess caused by Salmonella enteritidis]. PMID- 7986626 TI - Scientific method. PMID- 7986627 TI - Local analgesia in paedodontics. PMID- 7986628 TI - Local analgesia in paedodontics. PMID- 7986629 TI - Effectiveness of oral hygiene with and without root planing in treating subjects with chronic periodontitis. AB - The extent to which patients with chronic periodontitis could improve their condition by oral hygiene without instrumentation was investigated. Ten subjects were assessed, instructed in a subgingivally-directed oral hygiene technique (OH) twice a week until plaque was present at less than 20% of sites on two occasions and reassessed after 6 weeks when half the mouth was root planed. A final assessment took place after a further 6 weeks. At six weeks the mean number of sites with bleeding on probing (BOP) was significantly reduced (P < 0.001), the percentage of sites with BOP falling from 59% to 34%. In addition, an increase in gingival recession (P < 0.001) was accompanied by a reduction in mean probing depths (PD) (P < 0.05). The mean percentage reduction in sites with BOP was greatest for sites with probing depths less than 4 mm at baseline but even at sites with PD of 6 mm or more the mean BOP reduced from 81% to 57% of sites. Root planing at 6 weeks resulted in further significant reductions at 12 weeks in both BOP (to 10% of all sites) and in PD (P < 0.001), but there was little further change for the sites receiving OH alone. There was some evidence that this adjunctive effect of root planing was also present at sites with a PD less than 4 mm at baseline and at sites without retention factors at or below the gingival margin. The results indicate that patients with chronic periodontitis can improve their periodontal condition by OH alone even in deep pockets.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7986630 TI - Levels of burnout in general dental practitioners in the south-east of England. AB - There is some evidence to suggest that dentists suffer a high level of job related stress. Specifically, social interaction between dentist and patient is considered to be a type of job-related stress which may produce 'burnout', a syndrome of emotional exhaustion, depersonalisation and reduced personal accomplishment that can occur in individuals whose work involves close personal contact with their clients. A study was carried out during January to June 1992 to assess the levels of burnout, using the Maslach Burnout Inventory, in three samples of British GDPs recruited from the south-east of England. A total of 440 dentists were surveyed and 340 usable replies were returned. There were high levels of burnout in the British dentists. A number of demographic variables relating to marital status, educational status, time since qualification, numbers of dentists in the practice, number of days per week spent in practice and the proportion of NHS/private work undertaken were identified as being associated with some aspects of the burnout syndrome. PMID- 7986631 TI - Dental surgery assistants' roles in cross-infection control in general dental practice: their knowledge and use of autoclaves. AB - This study investigated dental surgery assistants' (DSAs) role in providing cross infection control in general dental practice. DSAs' knowledge about using autoclaves and their compliance with the recommended procedures were used as measures. Eighty-nine practices in three districts of the North Western Region of England were approached. Fifty-six agreed to permit the study and DSAs in these practices were observed at work and questioned, a response rate of 63%. Eighteen tasks relating to use of autoclaves (eg correct loading of instruments and correct storage) were observed and knowledge about them was assessed by questioning. Each was scored positively if correctly undertaken and answered. Scores for compliance varied between 2 and 12 and between 3 and 15 in the case of knowledge. In all instances certificated DSAs scored more highly than uncertificated DSAs. The study illustrated the value of certification, background education and membership of a vocational organisation. It supports the belief that all DSAs should be educated to the level of certification and that this improved education and training would improve cross-infection control in general dental practice. PMID- 7986632 TI - Mental nerve anaesthesia as a result of mandibular metastases of prostatic adenocarcinoma. AB - Three cases of mental nerve anaesthesia as a result of metastatic deposits from prostatic carcinoma are presented. They were referred to Consultant Oral and Maxillofacial Surgeons by alert GDPs. This highlights the fact that dental surgeons must be aware that systemic illness may manifest in the mouth and appropriate referral is essential. PMID- 7986633 TI - Dentistry in Norway. AB - Norway's health care system, which includes dentistry, is highly developed and well funded. In the light of the recently published Green paper, 'Improving NHS Dentistry' there are certain aspects of the delivery of both general dental care and orthodontic treatment in Norway which may be of interest to practitioners in the UK. PMID- 7986634 TI - The oral health challenge at the drawn of the third millennium. PMID- 7986635 TI - It takes many men (and women) to make a restoration. AB - From the patient's point of view a filling, is a filling, is a crown. There is, however, very much more to the 'simple filling' than that, as we all know but very rarely think about. PMID- 7986636 TI - [Surgical treatment of lateral clavicular fracture with the "clavicular hooked plate"]. AB - We know different surgical techniques for the treatment of lateral clavicle fractures (type 2 of the Neer-classification). Often an exercise stable osteosynthesis and early functional aftercare can be realized only with a jointconnecting transfixation (acromioclavicular joint). With a new osteosynthesis implant it is possible to solve the problems of this fracture with a save and relatively simple operation. The suggested implant guarantees an exercise-stable osteosynthesis that allows immediate functional aftercare. With this technique we can reduce the complication rate and reach full working capacity earlier. Within an observation period of about five years we used this implant on 21 patients and the clinical and radiological follow-up shows good to very good results in the medium and long-terms. PMID- 7986637 TI - [Anatomic reconstruction of posterior shoulder dislocation fractures. A new method using bone anchors]. AB - The posterior shoulder dislocation is often misdiagnosed. The overall cost in medical care is about six times higher than an anterior dislocation. For the precise diagnosis, correct x-rays in exact ap- and Y-view of the shoulder are essential. The ultimate analysis can be made by a CT-scan. An alternative method is presented to reconstruct the defects (reversed Hill-Sachs) by particular placing of anchors (Mitek). One to two years after, no recurrence of dislocations could be observed (9 cases). In two cases an arthroscopic mobilisation of the shoulder had to be done to regain full range of motion after 4 months. PMID- 7986638 TI - [Isolated fracture of the lesser tuberosity of the humerus: case reports and review of the literature]. AB - Only 17 cases of isolated avulsion fracture of the lesser tuberosity have been reported in the literature since Hartigan's report in 1895. Whereas in children, conservative treatment is almost successful, in adults operative restoration is the method of choice in order to obtain full painless range of motion with normal strength of muscle control. Surgical excision of the fragment of lesser tuberosity after failed conservative treatment may relieve the patient's symptoms. Three own cases and a review of the literature are discussed. PMID- 7986639 TI - [Pathogenesis of insertion tendinitis of the elbow in insurance medicine]. AB - The pathogenesis of insertion tendinosis of the elbow,--lateral as well as medial epicondylitis--is difficult to define precisely. Different hypotheses have been postulated with a correspondingly large number of alternative therapeutic proposals. At first view, the prime factor may be a repetitive stress of the groups of muscles involved, respectively of the extensors of the hand and the wrist. In fact, the etiology is multifactorial and includes a cluster of causes. A series of 661 cases of insertion tendinosis of the elbow--lateral and medial epicondylitis--seen over 16 years in a private outpatients-practice for either conservative or operative treatment has been analysed in groups sorted by age, profession, and association with other inflammatory or degenerative changes in the superior limbs. The accumulation of cases in the preclimacteric age (4th decade)--in male as well as in female patients--, and the increased frequency of association with other inflammatory or degenerative changes of the superior limbs (34%), shows the important role of age and constitution. In a smaller series of 289 cases, the subjective causes mentioned by the patients for being the source of their troubles were recorded. These dealt with different areas, such as various professional activities (whether manual labor or not), household work, practising certain sports, leisure time activities (e.g., handicrafts, gardening, needle work), and sometimes as a consequence of trauma. From the medical insurance point of view it results from these observations that the occupational factor alone practically never reaches the 75% causal level required by law in Switzerland for considering lateral or medial epicondylitis as an occupational disease. Likewise, an acceptance as a sequel of an accident is only exceptionally possible, as far as major tissue damages have been proved. PMID- 7986640 TI - [Long-term surgical results of osteochondrosis dissecans of the knee joint in adolescents less than 16 years of age]. AB - The correct therapy of osteochondritis dissecans in patients under 16 years is very important to prevent the knee joint from secondary arthritis. We analysed clinical, radiological and with MRI the long term (10 years) results of a follow up study on 36 patients under 16 years with 42 operatively treated osteochondritis dissecans of the knee joint. There were excellent and good results in 81% of the patients. After an average of 10 years there were no signs of arthritis which would necessitate any treatment. PMID- 7986641 TI - [High grade liver rupture--is nonsurgical therapy feasible?]. AB - Although well accepted in pediatric patients, the nonoperative management of severe blunt hepatic trauma in adults remains controversial. On the basis of 3 cases with major liver injury, the rationale and prerequisites for a successful nonoperative treatment are discussed. PMID- 7986642 TI - [Chronic pain sequelae after trauma of the cervical spine]. AB - This presentation summarises the opinions concerning chronic pain after mild cervical trauma without neurological and radiological findings. Clinicians are often surprised by the disabling character of the pain, despite the lack of severe lesions. The initial lesions lead in some cases to chronic headache having different features associated with cervical pain, but in our opinion this pain does not have a disabling nature. When the disabling character is present, we postulated that it is associated with other psychological, social and professional factors. In fact, the pathogenesis of this chronic disorder is multifactorial. Its treatment doesn't lead to healing but to better management of patient life with chronic pain. PMID- 7986643 TI - [International classification of damage, disability and handicap]. PMID- 7986644 TI - In situ cryofixation of kidney for electron probe X-ray microanalysis. AB - Cell physiological and pathophysiological studies often require information about the elemental composition of intracellular organelles in situ. Electron probe X ray microanalysis (EPXMA) is one of the few methods by which intracellular elemental content and distribution can be measured simultaneously. While several cryofixation techniques for EPXMA have been utilized on isolated cells, few have been applied successfully to whole tissue in vivo or in situ. A recently developed, commercial, portable, metal-mirror device was used for preserving kidney in situ to determine the intracellular element distribution in proximal tubule cells. Kidneys of male rats were exposed, cryofixed, and analyzed for organelle elemental contents by EPXMA imaging. In addition, some portions of the frozen tissue were prepared for conventional transmission electron microscopy. Proximal tubules were preserved with intact brush borders and open lumens. The quality of preservation of tubule cell organelles varied inversely as a function of depth from the point of first contact with the mirror surface; the best preservation was within 15 microns, while the poorest preservation was deeper than 30 microns. Analysis of EPXMA images from the best-preserved regions revealed that proximal tubule cell cytoplasmic K/Na was approximately 6, cytoplasmic Cl was low relative to other subcellular compartments, and mitochondrial Ca levels were 1.8 nmole/mg dry weight; these observations indicate that the cells were physiologically viable at the time of cryofixation. The advantages of in situ cryofixation by this metal-mirror method include acquisition of organelle elemental content data in vivo, ease of use, reproducibility, portability, applicability to other tissues, and suitability for pathophysiological studies. PMID- 7986645 TI - Structure of correctly self-assembled bluetongue virus-like particles. AB - Bluetongue virus-like particles (VLPs), synthesized by coexpression of VP2, VP3, VP5, and VP7 using recombinant baculoviruses, have been examined by cryoelectron microscopy and image analysis. The 3-D reconstruction of these VLPs reveals an icosahedral structure 86 nm in diameter with essentially the same features as for the native Bluetongue virus (BTV) particle. The VLP is thus shown to contain the four constituent proteins as the native virus particle, with each of the protein positions highly occupied. Since the BTV core-like particle formed by coexpression of VP3 and VP7 lacks five VP7 trimers around each of the five-fold axes, it appears that the presence of the outer capsid proteins VP2 and VP5 is necessary for the adhesion of these VP7 trimers around the five-fold axes. The observed spontaneous formation of complete VLP in the absence of the BTV nonstructural proteins implies that the nonstructural proteins are not necessary for the formation of the double-shelled viral capsid. However, the nonstructural proteins may be involved in different aspects of genome replication and packaging. PMID- 7986646 TI - A small angle X-ray scattering study of the binding of cyclosporin-A to calmodulin. AB - Small angle X-ray scattering (SAXS) was applied to the binding of the immunosuppressant drug cyclosporin-A to the protein calmodulin. Guinier analysis of the SAXS profiles yielded a radius of gyration, Rg, of 19.7 +/- 0.3 A for the native protein and 16.9 +/- 0.3 A for the drug/protein complex. Maximum entropy (maxent) methods of data analysis were used to calculate the distance distribution function, p(r). From this analysis, the Rg for the native protein is 20.9 +/- 0.1 A and that for the complex 16.7 +/- 0.1 A. The measured SAXS profiles and the derived p(r) for calmodulin agree with profiles calculated from the crystallographic structure of calmodulin. Major structural changes are induced in calmodulin on binding cyclosporin-A. A model consistent with the observed scattering profiles is an ellipsoid with major axes 55 and 36 A. Molecular modeling of the calmodulin molecule suggests that bond rotation in the flexible alpha-helix linker region produces models consistent with the above observations. PMID- 7986647 TI - In vitro maturation of prehead-like bacteriophage T4 polyheads: structural changes accompanying proteolytic cleavage and lattice expansion. AB - We have studied cleavage and expansion of the major T4 phage capsid protein gp23 (56 kDa) using polyheads, an aberrant, polymorphic tubular variant of bacteriophage T4D, as a model system. In a first step, we have cleaved the 65 amino-acid-long amino-terminal "delta piece" by limited proteolysis with Staphylococcus aureus V8 protease (type XVII) at exactly the same position, i.e., between residues 65 and 66, at which the phage-coded T4Ppase cleaves, to yield mature gp23* (48.7 kDa) without significantly affecting a second potential cleavage site between amino acids 142 and 143. Negatively stained preparations of thus cleaved polyheads revealed a near-hexagonal lattice with a 11.2-nm lattice constant. One-sided correlation averages of these cleaved/unexpanded polyheads yielded capsomeres that were rounder than those of prehead-like (i.e., uncleaved) control polyheads, with distinct trimers of mass (specifically, trimers of delta pieces in the area where three protomers are shared among three different capsomeres) removed, as revealed by difference maps computed from the correlation averages. Quantitative expansion of the 11.2-nm near-hexagonal lattice into the 13-nm near-hexagonal lattice characteristic of mature phage heads could be induced by pelleting the cleaved/unexpanded polyheads and resuspending them in water. This expansion step was inhibited by the presence of 100 mM phosphate. Cleavage of prehead-like polyheads to the 41-kDa gp23+ either between residues 142 and 143 by V8 protease or between residues 143 and 144 by trypsin rendered the polyheads unable to expand. In contrast, cleaved/expanded gp23* polyheads became resistant to cleavage to gp23+. As revealed by difference maps, the 7.3 kDa mass was additionally missing at the corners where the delta-piece trimers contact the protomers. PMID- 7986648 TI - Transmission electron microscopy of GroEL, GroES, and the symmetrical GroEL/ES complex. AB - Two new 2-D crystal forms of the Escherichia coli chaperone GroEL (cpn60) 2 x 7 mer have been produced using the negative staining-carbon film (NS-CF) technique. These 2-D crystals, which contain the cylindrical GroEL in side-on and end-on orientations, both possess p21 symmetry, with two molecules in the respective unit cells. The crystallographically averaged images correlate well with those obtained by other authors from single particle analysis of GroEL and our own previous crystallographic analysis. 2-D crystallization of the smaller chaperone GroES (cpn10) 7-mer has also been achieved using the NS-CF technique. Crystallographically averaged images of GroES single particle images indicate considerable variation in molecular shape, which is most likely due to varying molecular orientation on the carbon support film. The quaternary structure of GroES does, nevertheless, approximate to a ring-like shape. The complex formed by GroEL and GroES in the presence of ATP at room temperature has been shown to possess a symmetrical hollow ellipsoidal conformation. This symmetrical complex forms in the presence of a 2:1 or greater molar ratio of GroES:GroEL. At lower molar ratios linear chains of GroEL form, apparently linked by GroES in a 1:1 manner, which provide supportive evidence for the ability of both ends of the GroEL cylinder to interact with GroES. The apparent discrepancy between our data and that of other groups who have described an asymmetrical "bullet-shaped" (holo chaperone) GroEL/ES complex is discussed in detail. PMID- 7986649 TI - The repetitive microtubule-associated proteins MARP-1 and MARP-2 of Trypanosoma brucei. AB - The microtubular membrane skeleton of Trypanosoma brucei contains two closely related, repetitive, high-molecular-weight microtubule-associated proteins, MARP 1 and MARP-2 (MARP for Microtubule-Associated Repetitive Proteins). Their structure is unusual in that they consist of tandemly arranged, strongly conserved 38-amino-acid repeat units over almost their entire length of about 320 kDa. Their nonrepetitive N and C ends are comparatively short. The predicted amino acid sequences reveal a gradient of similarity between MARP-1 and MARP-2 which increases from the N-terminus (no significant similarity) through the repeat domain (50% similarity) to the C-terminus (94.5% similarity). Transfection of mammalian cell lines with recombinant fragments of MARP-2 demonstrate that the nonrepetitive C-terminus of MARP-2 binds specifically to microtubules. This C terminus does not show sequence similarity with any other microtubule-associated proteins and thus appears to represent a novel type of microtubule-binding domain. PMID- 7986650 TI - HIV-related training programs for health care professionals: findings from a collaborative assessment. AB - Seeking to avoid duplication of effort, evaluators from twelve separate HIV related training programs worked together to share information, assessment tools, measurement instruments, and preliminary findings across programs. Each training program focused on preparing health care professionals to meet the growing demands of the AIDS epidemic and specifically address psychosocial issues of care. The collaborative effort of program evaluators included an examination of experiences across programs and yielded recommendations for needs assessments, process evaluation procedures, and outcome measures. This paper focuses on the findings from an analysis of needs assessments and process evaluations across twelve HIV-related training programs in eleven areas of the country. PMID- 7986651 TI - Evaluation of two AIDS education programs for impoverished Latina women. AB - This paper evaluates and contrasts the effectiveness of two culturally sensitive AIDS education programs developed by the UCLA AIDS Nursing Network and delivered to 213 impoverished Latina homeless or drug-addicted women in Los Angeles. The Comprehensive Health Seeking and Coping Paradigm guided the program, which was implemented by specially trained Latina nurses and outreach workers. A quasi experimental design was employed where women were randomized by site into Specialized (N = 82) and Traditional (N = 131) programs. Repeated measures ANOVAS and log-linear models were used to evaluate improvement over a two-week period for women in both groups and to identify interactions with program type. Two-week posttest analyses were also conducted to assess program effectiveness, controlling for baseline values of the measure in question, nonequivalency between groups at baseline, and selected demographic characteristics, including acculturation. Results indicated that women in both AIDS education programs improved significantly in cognitive, behavioral, and psychologic outcomes. PMID- 7986652 TI - Examination and prediction of elementary school teachers' intentions to teach HIV/AIDS education. AB - Although studies have looked at school teachers' beliefs and attitudes toward AIDS and students with HIV/AIDS, none have specifically addressed teachers' intentions and attitudes toward teaching HIV/AIDS education. This study examines and predicts elementary school teachers' intentions to teach their students about HIV/AIDS. The postulates of the theories of reasoned action and planned behavior provided the framework for the examination of teachers' beliefs, attitudes, subjective norms, and perceived behavioral control regarding AIDS education. A sample of 198 elementary school teachers employed in the Commonwealth of Massachusetts completed self-administered questionnaires. Multiple regression analysis was used to predict intentions to teach HIV/AIDS, and to identify the determinants of intentions. Attitude, subjective norm, and perceived behavioral control, the variables of the theory of planned behavior, explained 64% of the variance in teachers' intentions; perceived behavioral control contributed the greatest weight to the prediction. Significant variance was additionally explained by three variables external to the theory of planned behavior: in service training, grade taught, and past HIV/AIDS teaching behavior. PMID- 7986653 TI - A developmental model for risk avoidance in adolescents confronting AIDS. AB - Epidemiologic studies indicate that HIV infection is on the rise within the adolescent population. Much of this increase has been attributed to the teenager's developmental proclivity for risk-taking behavior. Intervention programs designed to curtail high-risk behaviour among adolescents have focused primarily on educational methods alerting teenagers to modes of disease transmission. Among these programs, demonstration and role-playing techniques have shown promise, but have not significantly modified behavior patterns. In contrast, a new developmental technique known as previewing advocates the use of representation and enactment to promote risk deterrence. Previewing may serve as a productive alternative to traditional interventions, since it directly addresses the adolescent's cognitive limitations with regard to the prediction of behavioral outcomes. This paper recommends a prevention model using previewing that is designed to lower the incidence of AIDS transmission among adolescents. PMID- 7986655 TI - The risk of HIV infection for noninjecting sex partners of injecting drug users in Stockholm. AB - The risk for sexual transmission of HIV to noninjecting partners of injecting drug users in the course of their drug-using career was analyzed in a study of sexual behavior among 200 detained injecting drug users at the Remand Prison in Stockholm. Of the 194 who reported sexual intercourse during the last three years, 69% of the men and 41% of the women had had at least one noninjecting partner. Of the 119 with a regular partner at the time of arrest, 43% of the men and 8% of the women had a noninjecting regular partner. The HIV seroprevalence increased, whereas the proportion of noninjecting partners decreased with the duration of the drug-using career. Amphetamine injectors, who constitute the majority of drug injectors in Stockholm, reported a higher frequency of intercourse on drugs with regular partners than did the heroin users. The reported frequency of condom use was very low among the seronegative injectors, but somewhat higher among the seropositive injectors. The noninjecting regular sex partners can be said to share the risk for HIV infection along the course of the drug career of their injecting partners. PMID- 7986656 TI - Conspiracies, contagion, and compassion: trust and public reactions to AIDS. AB - AIDS educational programs can be effective only to the extent that they are perceived as credible by their target audiences. In this study, public trust associated with AIDS was assessed in a national telephone survey. African Americans were more likely than whites to express distrust of doctors and scientists concerning HIV transmission through casual contact, to believe that AIDS is being used as a form of genocide against minority groups, and to believe that information about AIDS is being withheld from the public. Individuals high in distrust did not differ from those low in distrust in their exposure to AIDS information. Higher levels of AIDS-related distrust were not related to self reported personal risk reduction, but were related to inaccurate beliefs about HIV transmission through casual contact and greater willingness to avoid and stigmatize people with AIDS. The importance of overcoming distrust in AIDS education programs is discussed. PMID- 7986654 TI - Prevalence and correlates of AIDS-related behavioral intentions among urban minority high school students. AB - Using data from a cross-sectional survey of 926 predominantly black and Hispanic ninth through twelfth graders in three New York City public high schools, the explanatory power of theoretically and empirically derived predictors (i.e., demographic, contextual, and cognitive) of intentions to engage in sexual intercourse, to be sexually monogamous, to use condoms during intercourse, and to ascertain intercourse partners' sexual and drug-use histories was compared. One third of sampled students "definitely" intended to have sexual intercourse in the next year, one-half "definitely" intended to be sexually monogamous, two-thirds "definitely" intended to use condoms during intercourse, and three-quarters "definitely" intended to ascertain intercourse partners' sexual and drug-use histories. In a predictive model including all investigated variables, those variables derived from the cognitive set (i.e., beliefs about susceptibility to getting AIDS, and beliefs about barriers, self-efficacy, norms, and values pertaining to AIDS-preventive actions) were most strongly associated with the four investigated behavioral intentions. However, certain variables derived from the demographic set (i.e., age, gender, race/ethnicity) and contextual set (i.e., previous behavioral involvement, cues, academic failure, substance use) also contributed explained variance to all four intentions. PMID- 7986657 TI - Pattern recognition analysis to the variation of nasal-pharynx cancer patients' trace element levels in samples of hair, whole blood, and tissue. AB - Pattern recognition has been used in this paper to analyze trace element levels in patients diagnosed with nasal-pharynx cancer (NPC) and in healthy control subjects. Trace elements such as Zn, Cu, Fe, Mn, and Mg have been tested in samples of hair and whole blood. Through Mahalanobis Distance Decision analysis, we have achieved good classification effects in whole blood samples: Efficiency for distinguishing patients in 96% and that of healthy controls is 90%. Classification hair samples is inferior to whole blood: Decision accuracy for patients is 58% and healthy controls is 90%. These results are also shown in a nonlinear mapping figure. At the same time, we have also determined 5 trace element levels in 16 other cancer patients' nonneoplastic and cancerous tissue, with no significant difference between them: Decision accuracy of cancerous tissue is 63%, and in nonneoplastic tissue is 50%, hence, we cannot identify them. It can be inferred that there is no idiosyncratic change of trace elements in cancer patients' neoplastic tissue, the change of a cancerous person may occur in the whole body. PMID- 7986658 TI - Manganese status, gut endogenous losses of manganese, and antioxidant enzyme activity in rats fed varying levels of manganese and fat. AB - We hypothesized that manganese deficient animals fed high vs moderate levels of polyunsaturated fat would either manifest evidence of increased oxidative stress or would experience compensatory changes in antioxidant enzymes and/or shifts in manganese utilization that result in decreased endogenous gut manganese losses. Rats (females in Study 1, males in Study 2, n = 8/treatment) were fed diets that contained 5 or 20% corn oil by weight and either 0.01 or 1.5 mumol manganese/g diet. In study 2, 54Mn complexed to albumin was injected into the portal vein to assess gut endogenous losses of manganese. The manganese deficient rats: 1. Had 30-50% lower liver, tibia, kidney, spleen, and pancreas manganese concentrations than manganese adequate rats; 2. Conserved manganese through approximately 70 fold reductions in endogenous fecal losses of manganese; 3. Had lower heart manganese superoxide dismutase (MnSOD) activity; and 4. Experienced only two minor compensatory changes in the activity of copper-zinc superoxide dismutase (CuZnSOD) and catalase. Gut endogenous losses of manganese tended to account for a smaller proportion of absorbed manganese in rats fed high-fat diets; otherwise fat intake had few effects on tissue manganese concentrations. PMID- 7986659 TI - Mechanism of cadmium-induced cytotoxicity in rat hepatocytes. Cd-induced acidification causes alkalinization accompanied by membrane damage. AB - Exposure of rat hepatocytes to cadmium below 50 microM for a short period (10 min) resulted in cellular acidification. Conversely, exposure to Cd more than 50 microM for a long period (60 min) caused cellular alkalinization accompanied by membrane damage as reflected by decrease in cellular K content and loss of intracellular lactic dehydrogenase. In hepatocytes exposed to 5 microM Cd, a concentration sufficient to induce acidification without cytotoxicity, the metal was preferentially associated with the crude nuclei and cell debris fractions, suggesting an interaction between Cd and cell membranes to cause acidification. Omission of bicarbonate from the incubation medium induced cellular acidification. The presence of Cd in this medium did not potentiate the medium induced acidification. Mg-ATP (25 microM) induced cellular acidification in relation to an increase in the concentration of cytosolic free Ca. The coexistence of Mg-ATP and Cd at the concentrations which had no effect on cellular pH in the presence of either agants induced cellular acidification. These observations suggest that Cd induced cellular acidification by modulating the process connected with the rise in cytosolic free Ca via interaction with plasma membranes. This acidification had no strong immediate cytotoxic actions but led to subsequent cellular alkalinization accompanied with severe cytotoxicity and membrane breakage. PMID- 7986660 TI - The interaction of the vanadyl (IV) cation with chondroitin sulfate A. AB - The interaction of VO2+ with the muchopolysaccharide chondroitin sulfate A (CSA) has been investigated by electron absorption spectroscopy and infrared measurements in aqueous solutions at different pH-values and ligand to metal ratios up to 6:1. The generation of a VO(CSA)2 species could be demonstrated. Coordination of the oxocation through the carboxylate group and the glycosidic oxygen of the D-glucuronate moieties is suggested. Infrared spectra of some poorly characterized solid VO/CSA complexes point to the same bonding characteristics. Preliminary results obtained at higher ligand to metal ratios suggest a different coordination behavior. PMID- 7986661 TI - Additive coclastogenicity of sodium selenite and caffeine in CHO cells treated with N-methyl-N'-nitro-N-nitrosoguanidine. AB - The clastogenic effect of N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) in Chinese hamster ovary (CHO) cells and its modulation by Na2SeO3 and caffeine were studied by metaphase analysis of chromosome aberrations (CA) as well as by measuring the formation and repair of single-strand (ss) DNA breaks employing hydroxylapatite chromatography. Treatment of CHO cells with MNNG (1.25 or 2.5 x 10-5M) for 3 h caused CA in 11 and 19% of metaphases scored, respectively. Pretreatment of cells with Na2SeO3 (1-5 micrograms/mL) or caffeine (0.2-2.0 mg/mL) for 2 h resulted in a 2-3.5-fold increase of CA frequency. Addition of both modulators during the mutagen exposure tended to cause a slight inhibition of clastogenic activity of MNNG (1.25 x 10(-5) M) or had no effect on CA number when MNNG was used at a concentration of 2.5 x 10(-5) M). Posttreatment of CHO cells with Na2SeO3 for 20 h after MNNG was ineffective in influencing the number of metaphases with CA, whereas, at these conditions, caffeine enhanced up to 6-7-fold the clastogenic activity of MNNG. Addition of both modulators during the whole experiment, 2 h pretreatment included, resulted in a further significant increase of CA frequency up to the total pulverization of chromosomes in all metaphases scored. The coclastogenic effect of caffeine was greater in this case. The enhancement of chromosome-damaging activity of MNNG by selenite and caffeine was better expressed when this carcinogen was applied at the higher concentration used. An additive coclastogenic effect was observed in CHO cells treated simultaneously with Na2SeO3 and caffeine plus MNNG.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7986662 TI - The antioxidant enzymes activity in the conditions of systemic hypersilicemia. AB - The effect of an excessive inorganic silicon oral intake on the activity of basic antioxidant enzymes was studied in rats. Activities of superoxide dismutase, catalase, and glutathione peroxidase were measured in liver and kidney tissues of animals receiving per os sodium metasilicate nonahydrate (Na2SiO3.9H2O) (Sigma, [St. Louis, MO]) dissolved in their drinking water. A decrease of the activity of all the studied enzymes was found in the samples derived from the experimental group. The results obtained indicate the free oxygen radicals participation in the potential pathologic events in the conditions of systemic hypersilicemia. PMID- 7986663 TI - The combined effect of high iron and zinc intake on copper status in rats. AB - The interactions between copper, zinc, and iron intake in rats were investigated with regard to copper status. Weanling male rats were fed purified diets containing two levels of each of the three elements in a 2(3) factorial design. The added amounts of copper, zinc, and iron in the diets were 5, 12, and 35 mg/kg feed or were 10 times as high. After feeding on the experimental diets for 4 wk, the rats were killed and copper concentrations in plasma and organs measured. Plasma copper concentration was lowered by high zinc and iron intakes but this was seen only in the rats fed the normal-copper instead of the high-copper diets. In essence, the effects of zinc and iron were additive. Neither in rats fed the normal-copper diets nor in those fed the high-copper diets did extra iron or zinc intake alter copper concentrations in liver, spleen, kidney, and tibia. PMID- 7986665 TI - Enantioselective syntheses and calcium channel modulating effects of (+)- and (-) 3-isopropyl 5-(4-methylphenethyll) 1,4-dihydro-2,6-dimethyl-4-(2-pyridyl)-3,5 pyridinedicarboxylates. AB - The (+)- and (-)-enantiomers of 3-isopropyl 5-(4-methylphenethyl) 1,4-dihydro-2,6 dimethyl-4-(2-pyridyl)-3,5-pyridinedicarboxylate were synthesized using an efficient highly enantioselective (ee > or = to 96%) variant of the Hantzsch dihydropyridine synthesis. The key step in this procedure involved the asymmetric Michael addition of a metalated chiral aminocrotonate, derived from D-valine or L valine, respectively, to the Knoevenagel acceptor (Z)-2-isopropoxycarbonyl-1-(2 pyridyl)-but-1-en-3-one. Both enantiomers exhibited a dual cardioselective partial calcium channel agonist (positive inotropic)/smooth muscle selective calcium channel antagonist effect. The relative in vitro smooth muscle calcium channel antagonist activities of the (-):(+) enantiomers was 26:1. In contrast, the (+)-enantiomer exhibited a greater in vitro positive inotropic effect on guinea pig left atrium where the contractile force was maximally increased by 14.8% at a concentration of 1.63 x 10(-8)M. PMID- 7986664 TI - Alterations in plasma total and high density lipoprotein cholesterol levels in hyperlipidemic rats fed diets with varied content of selenium and vitamin E. AB - The effect of dietary selenium and vitamin E on plasma total (TC) and high density lipoprotein cholesterol (HDLC) was evaluated in 54 Sprague Dawley rats fed cholesterol/cholic acid enriched diets. Diets 1, 2, and 3 had no added selenium (low Se) and 0 (low), 60 (adequate), and 600 (high) mg/kg dL alpha tocopheryl acetate added respectively. Sodium selenite at 0.2 mg/kg (adequate Se) was added to diets 4, 5, and 6 and at 4.0 mg/kg (toxic Se) to diet 7, 8, and 9 with the same pattern of vitamin E added to the diet as described above. TC and HDLC were measured using the Kodak Ectachem system. Rats in the low and adequate Se groups fed high vitamin E had lower TC values than rats fed lower vitamin E levels but differences were not significant. In the toxic Se groups, rats fed high vitamin E had significantly (p < 0.05) higher plasma TC values than did lower Vitamin E groups. Rats on the high vitamin E diets with low or adequate Se had significantly (p < 0.05) higher mean plasma HDLC values when compared to rats fed low or adequate vitamin E diets. HDLC values for animals on Se toxic diets were significantly (p < 0.05) lower in rats fed a low vitamin E diet. In rats fed Se deficient and adequate diets, a high vitamin E intake resulted in a decrease in TC and an increase in HDLC.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7986666 TI - Chiral copper(I)-thiolate clusters in metallothionein and glutathione. AB - Metallothionein (MT) is a ubiquitous mammalian protein comprising 61 or 62 nonaromatic amino acids of which 20 are cysteine residues. The high sulfhydryl content imparts to this protein a unique and remarkable ability to bind multiple metal ions in structurally significant metal-thiolate clusters. MT can bind seven divalent metal ions per protein molecule in two domains with exclusive tetrahedral metal coordination. The domain stoichiometries for the M7S20 structure are M4(Scys)11 (alpha domain) and M3(Scys)9 (beta domain). Up to 12 Cu(I) ions can displace the 7 Zn(2+) ions bound per molecule in Zn-MT. The incoming Cu(I) ions adopt a trigonal planar geometry with domain stoichiometries for the Cu12S20 structure of Cu6(Scys)11 and Cu6(Scys)9 for the alpha and beta domains, respectively. The circular dichroism (CD) spectra recorded as Cu+ is added to Zn-MT to form Cu12-MT directly report structural changes that take place in the metal binding region. The spectrum arises under charge transfer transitions between the cysteine S and the Cu(i); because the Cu(I)-thiolate cluster units are located within the chiral binding site, intensities in the CD spectrum are directly related to changes in the binding site. The CD technique clearly indicates stoichiometries of several Cu(I)-MT species. Model Cu(I) thiolate complexes, using the tripeptide glutathione as the sulfhydryl source, were examined by CD spectroscopy to obtain transition energies and the Cu(I) thiolate coordination geometries which correspond to these bands. Possible structures for the Cu(I)-thiolate clusters in the alpha and beta domains of Cu12 MT are proposed. PMID- 7986667 TI - Enantioselective disposition of oral amlodipine in healthy volunteers. AB - Plasma concentrations of (R)- and (S)-amlodipine were measured after single oral administrations to 18 healthy volunteers of 20 mg amlodipine racemate. The contribution of the pharmacologically active (S)-enantiomer to the concentrations of total amlodipine (sum of enantiomers) was significantly higher than that of the inactive (R)-enantiomer, with mean values of 47% R to 53% S for the Cmax and 41% R to 59% S for the AUC (range between 24% R:76% S and 50% R:50% S). The oral clearance of the active (S)-form was subject to much less intersubject variation (25% CV) than that of the inactive (R)-form (52% CV). (R)-Amlodipine was more rapidly eliminated from plasma than (S)-amlodipine, with mean terminal half-lives of 34.9 h (R) and 49.6 h (S). The terminal half-lives of total amlodipine (mean 44.2 h) were strongly correlated with--and thus highly predictive for--the half lives of the (S)-enantiomer. It is proposed that the observed enantioselectivity of oral amlodipine is due to differences in the systemic blood clearance of the enantiomers. PMID- 7986668 TI - Pharmacokinetics of ketoprofen enantiomers in monkeys following single and multiple oral administration. AB - Pharmacokinetic studies are reported after single oral administration of 3 mg/kg of stereochemically pure (S)-ketoprofen [(S)-KP] and (R)-ketoprofen [(R)-KP] to three male Cynomolgus monkeys and after repeated administration for 6 months of 3, 15 and 75 mg/kg/day of (S)-KP to both male and female monkeys. A high performance liquid chromatographic (HPLC) analysis was performed without derivatization of the samples, using a chiral column. The pharmacokinetic parameters for (S)-KP after administration of (S)-KP and for (R)-KP after administration of (R)-KP were, respectively, elimination half-life 2.32 +/- 0.36 and 1.64 +/- 0.40 h; oral clearance 3.50 +/- 0.66 and 7.50 +/- 3.20 ml/min/kg; apparent volume of distribution 0.74 +/- 0.24 and 1.16 +/- 0.76 liter/kg; mean residence time 1.79 +/- 0.77 and 1.41 +/- 0.65 h; area under the concentration/time curve 14.16 +/- 2.93 and 7.31 +/- 2.98 micrograms.h/ml. Forty nine percent unidirectional bioinversion of (R)-KP to (S)-KP was observed in this species and the pharmacokinetic parameters for the (S)-KP resulting from this inversion were also calculated. In the study of 6-month repeated administration of (S)-KP, linear pharmacokinetic behavior and no evidence of drug accumulation were observed at the three dose levels. PMID- 7986669 TI - Determination of the enantiomers of mianserin, desmethylmianserin, and 8 hydroxymianserin in the plasma and urine of mianserin-treated patients. AB - An HPLC method is presented which allows the measurement in the same run of the enantiomers of mianserin, desmethylmianserin, and 8-hydroxymianserin in plasma and urine of mianserin-treated patients. Limits of quantitation for the (S)- and (R)-enantiomers of mianserin and desmethylmianserin were 4 and 2.5 ng/ml, respectively, in plasma, and for the (S)- and (R)-enantiomers of mianserin, desmethylmianserin, and 8-hydroxymianserin 5, 2.5, and 5 ng/ml, respectively, in urine. The measured ratios of (S)-mianserin/(R)-mianserin and (S) desmethylmianserin/(R)-desmethylmianserin in the plasmas of 10 mianserin-treated patients, all extensive metabolizers of debrisoquine as determined by CYP2D6 genotyping, varied, respectively, from 1.0 to 4.06 and from 0.19 to 0.64. As the enantiomers of mianserin differ in their pharmacological profile, these results could partially explain why, until now, no consistent relationship has been established between the therapeutic response and total [(S) + (R)] plasma levels of this antidepressant. PMID- 7986670 TI - Chiral lumazines: preparation, properties, enantiomeric separation. AB - Optically active lumazines (biolumazine, dictyolumazine, monalumazine, and neolumazine) are prepared from the corresponding pterins by enzymatic reaction, using pterin deaminase excreted by Dictyostelium discoideum. The fluorescence properties, circular dichroism spectra, and chromatographic behavior of these lumazines are studied. D- and L-enantiomers of biolumazine, dictyolumazine, and monalumazine are separated using a chiral flavoprotein column. This column also separates the enantiomeric pterins of the threo form: monapterin and dictyopterin. However, the column does not separate the enantiomeric pterins of the erythro form: neopterin and biopterin. By coupling a reverse-phase column to the flavoprotein column, the separation of pterins and lumazines in function of their hydrophobicity, as well as the separation of the diastereomers, is achieved. This coupled achiral/chiral high-performance liquid chromatography method enables determination of the stereoconfiguration of natural lumazines by comparison with optically pure compounds. A lumazine derivative, present in the extracellular medium of Dictyostelium discoideum, is identified as D dictyolumazine, i.e., 6-(D-threo-1,2-dihydroxypropyl)-lumazine. PMID- 7986671 TI - Kinetics and stereochemistry of the microsomal epoxide hydrolase-catalyzed hydrolysis of cis-stilbene oxides. AB - The microsomal epoxide hydrolase (mEH)-catalyzed hydrolysis of cis-4,4' dimethylstilbene oxide (1a), cis-4,4'-diethylstilbene oxide (1b), cis-4,4' diisopropylstilbene oxide (1c), and cis-4,4'-dichlorostilbene oxide (1d) have been investigated using rabbit liver microsomal preparations. The kinetic parameters, Km and Vmax, and the absolute stereochemistry of the reactions have been determined and compared with those of cis-stilbene oxide (1e). All epoxides 1a-d are hydrolyzed by mEH with high product enantioselectivity to give (R,R)-(+) diols with ee > or = 90%. The presence of the substituents on the phenyl rings markedly reduces the rates of mEH catalyzed hydrolysis with respect to cis stilbene oxide, by increasing Km and reducing Vmax in the cases of 1a, 1b, and 1d, or reducing only the Vmax in the case of 1c. The very low Vmax, together with a persistent ability to fit into the mEH active site, make all these epoxides, and particularly 1c, inhibitors of cis-stilbene oxide hydrolysis. The kinetic and stereochemical results are interpreted on the basis of the proposed topology of the mEH active site. PMID- 7986672 TI - GABAB antagonists: resolution, absolute stereochemistry, and pharmacology of (R)- and (S)-phaclofen. AB - Phaclofen, which is the phosphonic acid analogue of the GABAB agonist (RS)-3-(4 chlorophenyl)-4-aminobutyric acid (baclofen), is a GABAB antagonist. As part of our studies on the structural requirements for activation and blockade of GABAB receptors, we have resolved phaclofen using chiral chromatographic techniques. The absolute stereochemistry of (-)-(R)-phaclofen was established by X-ray crystallographic analysis. (-)-(R)-Phaclofen was shown to inhibit the binding of [3H]-(R)-baclofen to GABAB receptor sites on rat cerebellar membranes (IC50 = 76 +/- 13 microM), whereas (+)-(S)-phaclofen was inactive in this binding assay (IC50 > 1000 microM). (-)-(R)-Phaclofen (200 microM) was equipotent with (RS) phaclofen (400 microM) in antagonizing the action of baclofen in rat cerebral cortical slices, while (+)-(S)-phaclofen (200 microM) was inactive. The structural similarity of the agonist (R)-baclofen and the antagonist (-)-(R) phaclofen suggests that these ligands interact with the GABAB receptor sites in a similar manner. Thus, it may be concluded that the different pharmacological effects of these compounds essentially result from the different spatial and proteolytic properties of their acid groups. PMID- 7986673 TI - Semipreparative enantiomeric separation of a series of putative melatonin receptor agents using tri-acetylcellulose as chiral stationary phase. AB - In order to obtain milligram amounts of the enantiomers of a series of compounds to be tested for binding to the melatonin binding site, a system for semipreparative enantiomeric separation was set up using tri-acetylcellulose as the chiral stationary phase. Interactions of this class of compounds with tri acetylcellulose were examined on an analytical scale with a series of 20 compounds. Apparently, both steric and electrostatic interactions determine retention behavior on tri-acetylcellulose. Semipreparative separations were carried out for a subset of seven compounds. The purity of the first eluting enantiomer usually was around 99%, whereas the purity of the second eluting enantiomer was slightly less. The system described is easy to use and has the major advantage that a series of compounds can be separated with one technique. The purities obtained are sufficient for a first screen of their affinity. PMID- 7986674 TI - Recovery of heat-injured Listeria monocytogenes. AB - Concern has been expressed that the ability of heat-injured Listeria monocytogenes cells to resuscitate during refrigerated storage of food may lead to underestimation of their heat resistance. The recovery of heat-injured L. monocytogenes was therefore examined as a function of incubation temperature and composition of recovery medium. Heat-injured cells exhibited a broad optimum temperature for recovery centered around 20-25 degrees C. The best recovery medium of those tested was blood agar. Incubation of cells in broth or chicken slurry at 5 degrees C (cold-enrichment) did not allow repair of potentially lethal injury i.e. it did not allow recovery of cells that would otherwise have died if incubated at a higher temperature. In some cases incubation of heat injured cells at 5 degrees C resulted in death of a proportion of the population. Repair of sublethal heat-injury, measured as the time of incubation in tryptone soya broth needed to regain the ability to grow on Listeria selective agar, was slower and less complete at 25 degrees C than at 2 degrees C; repair took 10-15 h at 25 degrees C compared with 8-12 days at 5 degrees C. Refrigeration of heat treated foods should not therefore increase the risk that heat-injured cells will recover from the heat treatment. PMID- 7986675 TI - Thermal resistance characteristics of PA 3679 in the temperature range of 110-121 degrees C as affected by pH, type of acidulant and substrate. AB - The influence of mushroom extract, acidification and type of acidulant (citric acid or glucono-delta-lactone) on the thermal resistance of PA 3679 spores has been studied. The pH values were 7 (phosphate buffer), 6.7 (non acidified mushroom extract), 6.22, 5.34 and 4.65 (acidified mushroom extract). Spores were less heat resistant in the non-acidified mushroom extract than in phosphate buffer. However, acidification of the extract had an effect on D values which was dependent on the specific pH. At pH 6.22, D values were higher than those in non acidified extract, for both type of acidulants, but the difference between D values in both substrates was affected by temperature, the higher the temperature, the less the difference. Acidification at other pH levels did not significantly affect D values obtained, neither did the type of acidulant. The z value ranged from 9.79 to 12.09 degrees C for citric acid and from 8.18 to 10.18 degrees C for glucono-delta-lactone. When pH was decreased the z value increased for both acidulants. PMID- 7986676 TI - Effect of processing conditions on acidification properties of wheat sour doughs. AB - The pH, total titratable acidity (TTA) and lactic and acetic acids production have been investigated for wheat sour doughs with and without yeast addition, inoculated with two strains of Lactobacillus plantarum (B33, B39). To study the effect of flour extraction rate (0.54, 11.11 and 1.68% ash content), dough yield (DY) (160, 200 and 240 of sour dough/100 g flour), and fermentation temperature (25, 30 and 35 degrees C) a response surface regression, factor analysis and K means clustering analysis were used. Results from factor analysis point out that the extraction rate of fluor governs TTA and acetic acid content; this factor accounts for the 53% of variability of the data. Dough yield is highly correlated with lactic acid content, explaining 27% of the total variance. Finally, temperature explains the remaining 16% of variation, but it is not related to any analytical variable. From K-means clustering analysis, flour extraction rate of 1.68% ash content leads to the highest TTA and acetic acid values, whereas DY of 240 g sour dough/100 g flour gives the greatest lactic acid content, and DY of 160 leads to the lowest levels of TTA and organic acids. PMID- 7986677 TI - Propionibacterium species diversity in Leerdammer cheese. AB - Thirteen 'classical' Propionibacterium strains, isolated from Leerdammer cheese samples, using three different media were characterized phenotypically. The phenotypic data of 74 tests, conducted on 27 propionibacteria, including four type, 10 reference strains and the 13 cheese isolates were analysed by numerical taxonomical techniques, using the simple matching coefficient and single linkage cluster analysis. All the strains were grouped in four major clusters, with a final linkage at the 81% S-level. The clusters were equated with the 'classical' P. acidipropionici, P. freudenreichii, P. jensenii and P. thoenii species. The species were identified by relating them to specific type strains and by comparison of phenotypic characteristics. Differential characteristics of each cluster were determined. Strains of P. acidipropionici, P. freudenreichii and P. jensenii, but no P. thoenii strains were isolated from the Leerdammer cheese samples. No 'cutaneous' propionibacteria were isolated. The largest cluster, representing 46% of the cheese isolates was equated with P. jensenii. Various red/brown pigmented strains, which could be identified as the old 'P. rubrum' species were isolated from the cheese. These strains were, however, phenotypically identified as P. jensenii and also grouped in the P. jensenii cluster. PMID- 7986678 TI - Effect of trisodium phosphate on biofilm and planktonic cells of Campylobacter jejuni, Escherichia coli O157: H7, Listeria monocytogenes and Salmonella typhimurium. AB - Trisodium phosphate (TSP) has been approved by the United States Department of Agriculture as a post-chill antimicrobial treatment for raw poultry. This study examines the effectiveness of TSP against planktonic (suspended) and biofilm (attached) cells of Campylobacter jejuni, Escherichia coli O157:H7, Listeria monocytogenes and Salmonella typhimurium at room temperature (RT) and 10 degrees C. At either temperature E. coli O157:H7 was the most sensitive to TSP treatments; 10(6) cfu/ml of planktonic or 10(5) cfu/cm2 of biofilm cells were eliminated by a 30 s treatment with 1% TSP. Campylobacter jejuni was slightly less sensitive. Listeria monocytogenes was the most resistant to the effect of TSP, requiring exposure to 8% TSP for 10 min (RT) or 20 min (10 degrees C) to reduce biofilm bacteria by at least one log. Biofilm cells of S. typhimurium and Listeria monocytogenes were more resistant than planktonic cells. Salmonella typhimurium was more sensitive to treatments using TSP at 10 degrees C than at RT. In contrast, L. monocytogenes was more resistant to TSP at 10 degrees C. Trisodium phosphate appears to be an effective treatment for reducing populations of C. jejuni, E. coli O157:H7 and S. typhimurium. This product has the potential to be used for reduction of bacterial counts on other food products besides raw poultry or on food and non-food contact surfaces. PMID- 7986679 TI - A comparison of six different plating media used in the isolation of Salmonella. AB - Seventeen Canadian Federal, Provincial and Public Health Laboratories took part in different phases of a comparative/collaborative study that evaluated rapid methods to the standard Health Protection Branch (HPB) method for the detection of Salmonella. A variety of commercial media were tested, including Brilliant Green Sulpha Agar, Bismuth Sulphite Agar, Hektoen Enteric Agar, Xylose Lysine Deoxycholate Agar, EF-18 Agar and Rambach Agar. Each laboratory compared up to six of these different plating media. Plating of 123 salmonellae cultures and 28 artificially-inoculated foods showed the recovery of Salmonella spp. on the six plating media to be within one log. Therefore, quantitative testing of the media showed them to be comparable in the recovery of salmonellae. Qualitative testing of the six media during the comparative/collaborative study of various methods showed that EF-18 Agar recovered the greatest number of isolates. Hektoen Enteric Agar ranked second, with the other agars being comparable in their recovery of Salmonella spp. Problems with the various media are summarized. Based on our results and those of other researchers, it is recommended that Bismuth Sulphite Agar be compulsory and that at least one other agar be used for newly developed cultural procedures. PMID- 7986680 TI - Comparison of media for enumerating osmotolerant yeasts in orange juice concentrates. AB - Enumeration of osmotolerant yeasts in high-sugar food products can be improved by using diluents and recovery media formulated to closely resemble their natural environment. Heat and freeze-stressed yeasts often exhibit decreased tolerance to acetic pH and selective agents, thus requiring optimum recovery conditions for enumeration. The study reported here was done to evaluate three methods for their suitability to enumerate osmotolerant yeasts from fifty Venezuelan orange juice concentrates. Yeasts were enumerated by surface plating serially diluted samples on plate count agar containing 52% (w/w) sucrose (PCAS 52) and incubating at 32 degrees C for 6 days; pour plating in yeast extract malt extract agar containing 52% (w/w) sucrose (YEMS 52) and incubating at 32 degrees C for 6 days and pour plating in potato dextrose agar (PDA), pH 3.5, and incubating at 25 degrees C for 5 days. Mean populations of yeasts recovered were: 4.2 x 10(5), 5.3 x 10(4) and 7.5 x 10(3) cfu/ml, respectively, on PCAS 52, YEMS 52 and PDA. High recovery on PCAS 52 is attributed to avoidance of osmotic shock and possible secondary lethal effects of high temperature, which may be associated with pour plating techniques. Significantly (P < 0.05) higher population were recovered on PCAS 52 than on YEMS 52 and PDA. Predominant osmotolerant yeasts were Saccharomyces bisporus var. mellis, recently named Zygosacharomyces rouxii (Kreger-van Rij W.J.W. (1984) The Yeasts: A Taxonomic Study). PMID- 7986681 TI - Heat resistant fungi isolated from soil. AB - The Thermal death time values (TDT) were estimated for Dichotomomyces cejpii, Gilmaniella humicola, Talaromyces avellaneus and Talaromyces bacillisporus isolated from soil. TDT values were compared with the TDT values of the known heat-resistant species, Byssochlamys nivea, Neosartorya fischeri and Talaromyces flavus. All species studied showed considerable heat resistance. The most resistant species Talaromyces avellaneus (172 cfu, initial concentration) of the isolates with unknown heat resistance withstood 90 degrees C for 10 min. Byssochlamys nivea appeared to be the most sensitive species under our experimental conditions. PMID- 7986682 TI - Epidemiology of mycosis fungoides. AB - Study of the epidemiology of mycosis fungoides has been hampered by methodologic issues. Mycosis fungoides does appear to be increasing in frequency more rapidly than lymphoma in general. There is substantial geographic variation, as well as variation by race and gender. Analytic studies have not demonstrated additional risk factors. PMID- 7986683 TI - The role of human T-cell lymphotropic viruses (HTLV-I and II) in cutaneous T-cell lymphomas. AB - Although an association between the human T cell lymphotropic viruses (HTLV-I and II) and cutaneous T cell lymphoma (CTCL) has long been suspected, only a minor fraction of patients with this disease have antibodies to the viral structural proteins. However, the consistent finding of HTLV-like particles in cultures of peripheral blood mononuclear cells (PBMC) from such patients has prompted a continued effort to find evidence linking the virus to this disease. Capitalizing on the increased sensitivity afforded by combining PCR amplification with detection by Southern blot hybridization, it became possible to demonstrate HTLV tax and/or pol proviral sequences in freshly isolated PBMC of most patients with mycosis fungoides. These observations suggest a possible role of the virus in the pathogenesis of CTCL, and may impact on diagnostic and therapeutic measures in the future. PMID- 7986684 TI - Review of investigative diagnostic techniques for cutaneous lymphoma. AB - This article reviews the contribution of modern investigative techniques to the diagnosis of cutaneous lymphoproliferative diseases. Special attention is given to the significance of immunoglobulin and T-cell receptor rearrangements; as detected by Southern blotting and/or the polymerase chain reaction. Additional topics discussed include immunohistochemistry, cytogenetics, onco- and tumour suppressor genes and in-situ hybridization. It is recommended that the results of these techniques are interpreted in the form of a multifaceted diagnostic profile. PMID- 7986685 TI - Cutaneous lymphomas other than mycosis fungoides. PMID- 7986686 TI - CD30+ anaplastic large cell lymphomas. AB - Within the spectrum of CD30+ lymphoproliferative diseases of the skin primary cutaneous CD30+ large cell lymphomas are now recognized as a distinct clinicopathologic entity. Once terminologic confusions are clarified the pertinent clinical, histomorphological, and immunophenotypical features essential for the diagnosis can be delineated. Clinical studies indicate a better prognosis of primary cutaneous CD30+ large cell lymphomas as compared with their nodal counterparts and with other cutaneous large cell lymphomas. Therapeutic strategies should be planned accordingly. PMID- 7986687 TI - Cutaneous pseudolymphomas: classification and differential diagnosis. AB - Cutaneous pseudolymphomas are benign hyperplastic lymphoproliferative reactions that simulate cutaneous malignant lymphomas clinically and/or histologically. The differentiation between cutaneous pseudolymphomas and primary cutaneous lymphomas is often very difficult, but is important because it has therapeutic consequences. The term pseudolymphoma does not refer to a specific disease, but to a heterogeneous group of pseudo-B-cell lymphomas and pseudo-T-cell lymphomas. In this article clinical and histological features of this group of disorders will be discussed and the differential diagnostic criteria, that have been used in the past decades to differentiate between cutaneous lymphomas and pseudolymphomas will be critically evaluated. PMID- 7986688 TI - Lymphomatoid papulosis: a follow-up study of 41 patients. AB - Forty-one patients with lymphomatoid papulosis have been followed from 1 to 22 years (mean 11.4 years, median 10 years). Six patients developed malignant lymphoma, 3 cutaneous T-cell lymphoma, 2 Ki-1 large cell lymphoma, and 1 Hodgkin's disease. A clinical malignant presentation combined with the finding of aneuploidy in skin lesions seem to be indications of a malignant potential. Treatment with methotrexate in low dosage is an efficient treatment of lymphomatoid papulosis and probably diminishes the risk of malignancy. PMID- 7986689 TI - Topical carmustine (BCNU) for patch/plaque mycosis fungoides. AB - This article summarizes experience with topical carmustine (BCNU) solution in 172 patients with patch/plaque stage mycosis fungoides. At 36 months 92% of stage-T1 (less than 10% skin involvement) and 64% of stage-T2 (10% or more skin involvement) patients were either in complete or partial remission. The most frequent side effect was an erythematous reaction which was followed by a benign type telangiectasia in some patients. No secondary skin cancers were seen. Bone marrow depression was uncommon. Topical BCNU is an effective treatment for patch/plaque stage mycosis fungoides. PMID- 7986690 TI - Treatment of cutaneous T-cell lymphoma. AB - A review of current therapy for cutaneous T-cell lymphoma (CTCL) (mycosis fungoides and erythrodermic CTCL) is presented. Treatments for mycosis fungoides limited to the skin include topical steroids, mechlorethamine (nitrogen mustard) and carmustine (BCNU), electron beam radiation, low-dose methotrexate, and interferon-alpha (IFN). Treatments for erythrodermic CTCL include low-dose methotrexate, IFN, extracorporeal photopheresis, and single agent or combination chemotherapy. Treatment for systemic CTCL includes IFN, single or combination chemotherapy, and combined modalities. Newer therapies are reviewed. Whereas prognosis for patients with disease limited to the skin is generally good, that for those with nodal or visceral lymphoma is mostly unfavorable. Controversial issues relating to total skin versus local treatment, prolonged maintenance versus intermittent therapy, and aggressive versus conservative treatment of early stage disease are discussed. The UCSF approach to treatment of CTCL and lymphomatoid papulosis is presented. PMID- 7986691 TI - Comparative study of cutaneous T-cell lymphoma and adult T-cell leukemia/lymphoma. AB - An important disease entity distinct from cutaneous T-cell lymphoma (CTCL) in Japan is adult T-cell leukemia/lymphoma (ATL), which shows almost the same phenotype as CTCL, ie, a helper/inducer T-cell phenotype (CD4-positive, CD8 negative), and usually involves the skin. This article describes differences between CTCL and ATL in terms of clinical and immunopathologic cell surface features. In patients with ATL, the predominant physical findings were lymph node, bone marrow and skin involvement, hepatosplenomegaly, leukemic manifestations, and an aggressive course. In patients with CTCL, in contrast, only skin lesions predominated at the onset of the disease and a relatively good prognosis was shown. The predominant phenotype of the neoplastic cells in the skin of patients with CTCL was CD3+, CD4+, CD29+, CD45RO+, HLA-DR+, HLA-DQ+, CD7 , L-selectin-, and CD45RA-. Some phenotypic discrepancy was found between the neoplastic cells in the peripheral blood, lymph nodes and skin of patients with ATL with respect to CD45RA and CD45RO, and CD7, CD29, CD25, and HLA-DR. That is, the predominant neoplastic cell phenotype was helper T-cell, which was CD3+, CD4+, L-selectin+, CD25+, CD45RA+, HLA-DR+, CD29-, and CD45RO- in peripheral blood, and CD3+, CD4+, L-selectin+, CD29+, CD45RO+, HLA-DR+, and CD45RA- in the skin and lymph nodes. Phenotypic heterogeneity of ATL cells and heterogeneity of CD45R isoform expression on ATL cells were evident in different organs. These findings confirm that the difference in antigen expression on the cell surface might reflect the clinical features of ATL and CTCL. CTCL cells do not share the same phenotype as ATL cells. PMID- 7986692 TI - Clinical, histopathologic, and immunohistochemical correlations in leukemia cutis. AB - Specific (leukemia cutis) and nonspecific (reactive or secondary) skin lesions are associated with systemic leukemia. The following categories of leukemia cutis are discussed in this article: myelogenous (granulocytic) leukemia, monocytic leukemia, myelomonocytic leukemia, lymphocytic and lymphoblastic leukemia, hairy cell leukemia, and adult T-cell leukemia/lymphoma. The temporal relationship between the diagnoses of systemic leukemia and leukemia cutis, the course, and the prognosis are also discussed. Other sites of extramedullary involvement are correlated with leukemia cutis. The appearance of specific skin lesions in leukemia is usually associated with a very poor prognosis. PMID- 7986694 TI - Veterinary public health. Rabies control in Baltic countries. PMID- 7986693 TI - Dengue and dengue haemorrhagic fever. PMID- 7986695 TI - Expanded programme on immunization (EPI). Progress towards poliomyelitis eradication, 1976-1993. PMID- 7986696 TI - WHO case definitions for AIDS surveillance in adults and adolescents. PMID- 7986697 TI - Environmental health. Gold, mercury and health. PMID- 7986698 TI - Special provisions relating to each of the diseases subject to the regulations. Chapter I--plague. PMID- 7986699 TI - Relapse following fixed duration treatment for multibacillary leprosy. PMID- 7986700 TI - Expanded programme on immunization. Missed opportunity survey. PMID- 7986701 TI - American Association for Cancer Education. 28th annual meeting. November 17-20, 1994, Louisville, Kentucky. Abstracts. PMID- 7986702 TI - Controversies in breast MRI. AB - This article addresses some of the current controversies in breast magnetic resonance imaging (MRI), including (a) Is MR mammography a suitable magnetic resonance imaging (MRI), including (a) Is MR mammography a suitable name for breast MRI? (b) Do we need another breast-imaging exam (Is mammography really that bad?)? (c) What is the best technique for MRI of the breast? (d) Is fat suppression necessary? (e) Is MRI more sensitive than mammography for breast cancer detection? (f) Will MRI make a difference in patient outcome, and will it become a screening test? (g) What are the current indications for breast MRI? (h) Is MRI important for evaluation of the post-surgical breast? and (i) Should patients with radiographically dense breast undergo "screening" MRI? PMID- 7986703 TI - Interventional use of magnetic resonance imaging. AB - Among the currently available imaging techniques, magnetic resonance imaging (MRI) offers particular advantages for guiding, monitoring, and controlling diagnostic and therapeutic interventions, with particular appeal for most of the minimally invasive, minimal access approaches. The most obvious role of MRI is in monitoring and controlling a variety of interstitial ablative procedures, utilizing methods including thermal therapy (interstitial laser therapy, cryosurgery, focused ultrasound surgery). A fundamental requirement of MR monitoring is the implementation of pulse sequences with appropriate spatial and temporal resolution as well as overall image quality suitable for the dynamic imaging task. In addition, there is a need for a more accessible magnet configuration to enable execution of various interventional procedures. MR compatibility of instruments and devices, therefore, needs to be addressed, as must the integration of therapy delivery modalities with the MR system. PMID- 7986704 TI - Contrast-enhanced magnetic resonance imaging of the abdomen. AB - The use of intravenous gadolinium chelates in imaging of the abdomen is helpful in the detection and characterization of disease entities. It is well recognized that magnetic resonance (MR) imaging is more sensitive to the presence or absence of gadolinium chelates than computed tomography is to iodine. By exploiting this strength of gadolinium and MR sequences that reduce artifacts, the usefulness of abdominal MR examinations can be maximized. As a nonspecific extracellular contrast agent, the enhancement of gadolinium chelates reflect blood delivery (capillary phase imaging), capillary permeability (interstitial enhancement), and venous drainage (late interstitial/washout enhancement). In general terms, MR evaluation of abdominal organs is benefited by imaging in both capillary and interstitial phases of enhancement since these separate phases reflect different physiological aspects of disease processes. In this review, optimized investigation using intravenous gadolinium chelates is described for diseases of the kidney, gastrointestinal tract, liver, gallbladder, pancreas, spleen, and adrenal glands. The use of newer intravenous and oral contrast agents, particularly relating to the investigation of bowel and liver diseases, is also discussed. PMID- 7986705 TI - The anti-apoptotic role of infectious agents in lymphoid malignancies characterized by c-myc deregulation. PMID- 7986706 TI - Effect of recombinant human interleukin-3 on haematological recovery from chemotherapy-induced myelosuppression. AB - Patients with non-small-cell lung cancer (NSCLC) were treated with ICE chemotherapy (ifosfamide 2000 mg/m2, days 1-3; carboplatin 300 mg/m2, day 1; etoposide 75 mg/m2, days 1-3) intravenously (i.v.) during the first 3 d of a maximum of four 28 d treatment cycles. Interleukin-3 (IL-3) was administered in cycles 2 and 4 as a daily subcutaneous (s.c.) injection on days 5-18. Cohorts of three patients were treated at dosage levels of 0.5, 1.25, 2.5, 5.0, 10.0 and 15.0 micrograms/kg/d. At 15.0 micrograms/kg/d a 'flu-like' syndrome of myalgias, arthralgias and fatigue was considered dose-limiting. Other toxicities were headache, fever, urticaria, arrhythmia, chills and flushing. Subsequently, nine patients were added to the group receiving 10 micrograms/kg/d. 27 patients received IL-3 after their second course of ICE. At 10 and 15 micrograms/kg/d, IL 3 in cycle 2 was associated with enhanced haematological recovery. Depth of neutrophil nadir and days of neutropenia (ANC < 0.5 x 10(9)/l) were reduced in 9/13 patients and in 8/11 patients, respectively. No effect was seen on platelet nadir or days of thrombocytopenia. IL-3 was well tolerated up to 10 micrograms/kg/d when given as a daily s.c. injection. Results suggest IL-3 as a potential adjunct to chemotherapy, and further studies to explore administration of IL-3 in combination with other cytokines in this setting are warranted. PMID- 7986707 TI - Accessory cells mediate hairy-cell proliferation by mechanism(s) involving both adhesion and TNF alpha secretion. AB - The mechanisms responsible for hairy-cell (HC) growth both in vitro and in vivo are still unclear. In a recent study we showed that monocytes/macrophages induce HC proliferation in vitro. The purpose of the present paper is to examine the specificity of this accessory cell effect and to establish the mechanism(s) involved. We demonstrate that the effect is not confined to monocytes/macrophages but is also potentially seen with a range of other cell types. However, at low accessory cell:HC ratios (< 1:20) only human umbilical vein endothelial cells (HUVEC) and macrophages induce HC proliferation. We suggest that these observations are of pathophysiological significance in relation to the close association frequently observed between HCs and endothelial cells/macrophages in the liver and spleen of patients with hairy-cell leukaemia (HCL). Regarding the mechanisms of the accessory cell effect, we show that both soluble factors and cell contact are important. A blocking anti-TNF alpha antibody abrogated the HC proliferation induced by HUVEC supernatant, indicating the involvement of this cytokine. Interaction of HCs with HUVEC via CD11b and 11c leucocyte integrins was shown to be important in the contact effect. Our demonstration of the involvement of both cytokines and cell contact in HC proliferation is in accord with what is already known about the control of B-cell growth and differentiation. More specifically, our results suggest that TNF alpha and interaction with endothelial cells/macrophages via leucocyte integrins are involved in the proliferation of late B-cells of the maturational stage represented by HCs. PMID- 7986708 TI - Erythropoietin response to anaemia is not altered by surgery or recombinant human erythropoietin therapy. AB - Recombinant human erythropoietin (EPO) therapy has been shown to increase red blood cell (RBC) production and facilitate autologous blood donation before elective surgery. However, recent reports have suggested that surgery and/or EPO therapy may suppress endogenous erythropoietin secretion in response to anaemia. We therefore analysed the haemoglobin/erythropoietin relationship preoperatively and postoperatively in 71 autologous blood donors subjected to aggressive phlebotomy and six treatments with either EPO (150 U/kg, n = 16, 300 U/kg, n = 18, or 600 U/kg, n = 19) or placebo (n = 18). Using data from the three preoperative study visits, the linear relationship between log erythropoietin and haemoglobin was determined for each of the 18 placebo patients. We found no significant differences in the slopes of the relationships in this group during aggressive phlebotomy. Furthermore, there was no evidence of a significant difference in the erythropoietin level recorded postoperatively for each patient to that predicted from the patient's postoperative haemoglobin level, based on the haemoglobin/log erythropoietin relationship preoperatively. Similarly, for each of the EPO-treated groups, there was no evidence of a significant difference when comparing the recorded erythropoietin level to that predicted from each patient's postoperative haemoglobin level, based on the haemoglobin/log erythropoietin relationship preoperatively. We conclude that preoperative recombinant human erythropoietin therapy and/or surgery do not adversely affect the postoperative erythropoietin response to anaemia. PMID- 7986709 TI - Recombinant human interleukin-3: pharmacokinetics after intravenous and subcutaneous bolus injection and effects on granulocyte kinetics. AB - The pharmacokinetics of E. coli derived recombinant human interleukin-3 (rhIL-3) was studied following intravenous (i.v.) and subcutaneous (s.c.) bolus injection of rhIL-3. After i.v. bolus injection in eight patients, serum peak levels of 34.5-135.0 ng/ml were reached, followed by a rapid decline with a t1/2 alpha of 17 +/- 2 min and a t1/2 beta of 59 +/- 7 min. After s.c. bolus injection in five patients, the absorption was more prolonged with peak serum levels reached at 2.8 +/- 0.4 h. Elimination was also more protracted, and serum base-line levels were reached at 14-24 h. The immediate effect of rhIL-3 on peripheral white blood cells was less pronounced and more variable than previously found for G- or GM CSF. Following i.v. administration, neutrophils showed a moderate drop to median 64% of initial values (range 42-85%) at median 30 min after injection (range 15 60 min) followed by an increase at 24 h to 69-288% of initial values. Eosinophils dropped to a median nadir of 34% and then gradually increased to maximum values in the range 135-720% at 18-24 h. The effect of rhIL-3 was further examined following i.v. injection of autologous 111Indium-labelled granulocytes in six patients. In steady state, i.v. injection of rhIL-3 caused a moderate drop in 111Indium activity of peripheral blood within 20 min without tendency to subsequent recovery. No change occurred in the activity recorded over the lungs and liver. The activity over the spleen decreased moderately in two patients. These results are strikingly different from those previously obtained after i.v. injection of rhGM-CSF. PMID- 7986710 TI - Blast cells in child and adult AML: comparative study of morphocytochemical, immunological and cytogenetic characteristics. AB - Bone marrow blast cells of 174 child and 188 adult patients with AML were examined and characterized in terms of their FAB type, immunological phenotype (102 children, 123 adults) and karyotype (69 children, 95 adults). The incidence of FAB variants of AML proved similar in children and adults. In patients under 15 and over 60, peroxidase activity in myeloblasts was lower than in middle-aged patients. Similar rates of HLA-Dr. Thy-1, CD11a, T-cell antigens, CD19, Gly-A and Eb antigens were found in cells of child and adult patients. The frequency of CD11b, CD38 and CD10 antigen expression on blast cells was higher in children than in adults. Abnormal blast karyotype was noted in 81.8% of children and 73.7% of adults. Translocation (8;21) was usually found in cases of M2 type (82%), significantly more frequently in children. predominantly in the group aged 6-10. t(15;17) was detected in all age groups only in M3 type of cells (86%). t(9;22) occurred more frequently in adults than in children; t(11q23) incidence rates were somewhat higher in children than in adults. Three cases of AML in children are described with deletion of chromosome 5 in their leukaemic cells. The data obtained indicate different biological characteristics of blast cells in children and adults. It is likely that haemopoietic cell involvement in children under 2 years and adult patients over 60 occurs at earlier stages than in middle-aged patients. PMID- 7986711 TI - Phosphorylation of 2-chlorodeoxyadenosine (CdA) in extracts of peripheral blood mononuclear cells of leukaemic patients. AB - 2-Chlorodeoxyadenosine (CdA) is an antileukaemic agent used in treatment of hairy cell leukaemia (HCL) and chronic lymphocytic leukaemia of B- and T-cell type (B CLL and T-CLL). The aim of this study was to elucidate the interpatient variability of CdA phosphorylation and its relation to response to CdA treatment. In extracts of peripheral blood mononuclear cells of patients with B-CLL (n = 39), CdA phosphorylation was significantly higher than in HCL (n = 19) when calculated per protein (391 +/- 155 pmol CdA phosphorylated/mg protein/min versus 288 +/- 166 pmol/mg/min, P < 0.001), but was the same when calculated per cell (12 +/- 5.9 pmol/10(6) cells/min versus 14 +/- 5.9 pmol/10(6) cells/min) due to a larger cell volume in HCL. In T-CLL (n = 6), CdA phosphorylation was significantly lower than in B-CLL, both when calculated per protein (128 +/- 68 pmol/mg/min, P < 0.001) or per cell (5.7 +/- 2.7 pmol/10(6) cells/min, P < 0.05). This low CdA phosphorylation in T-CLL was unexpected because normal B- and T lymphocytes contain equal amounts of CdA phosphorylation. With B-CLL, 21 patients who responded (complete and partial response) to CdA treatment showed a significantly higher CdA phosphorylation than 13 patients not responding to CdA treatment (456 +/- 170 pmol/mg/min versus 309 +/- 97 pmol/mg/min, P < 0.01). We conclude that the level of CdA phosphorylation is correlated with the response of leukaemias to CdA treatment. PMID- 7986712 TI - Expression of shared idiotypes by paraproteins from patients with monoclonal gammopathy of undetermined significance. AB - We have previously demonstrated the expression of shared idiotypes by the paraproteins from approximately one-quarter of patients with multiple myeloma (MM). We have now investigated whether similar cross-reactivity is expressed in the paraproteins of patients with monoclonal gammopathy of undetermined significance (MGUS), using a panel of 32 monoclonal antibodies (MAB) generated against follicular B cell lymphomas. The paraproteins from 76/409 (19%) patients with MGUS reacted with at least one of 23 different anti-idiotypic antibodies used in this study. 18 MABs demonstrated reactivity with more than one patient's paraprotein. Moreover, 10 MABs reacted frequently (with 5-22 paraproteins). Over half (41/76) of the reactive patients' paraproteins reacted with more than one MAB from this panel. This frequency of anti-idiotypic reactivity was similar to that of previously studied patients with myeloma, chronic lymphocytic leukaemia (CLL), and follicular B-cell lymphomas. There was no correlation between specific anti-idiotypic reactivity and the propensity to develop serious disease (MM, macroglobulinaemia, amyloidosis, or other lymphoproliferative disorders) in patients with MGUS. These results suggest that MGUS is derived from cells producing antibodies that are similar to those of other B-cell malignancies and that the pattern of idiotype expression is irrelevant to malignant potential. PMID- 7986713 TI - Subgroup and cost-benefit analysis of the Finnish multicentre trial of clodronate in multiple myeloma. Finnish Leukaemia Group. AB - Osteolytic lesions and pathological fractures are the major problems in the clinical management of multiple myeloma. We previously reported the main results of a randomized, controlled multicentre trial in 350 Finnish patients with multiple myeloma. All patients received standard melphalan-prednisolone treatment and were randomized to receive either clodronate 2.4 g daily or a placebo for 24 months. The proportion of patients with progression of osteolytic bone lesions was twice as high in the placebo group as in the clodronate group (24.0% v 12.0%, P = 0.026). The purpose of the present study was to investigate factors associated with the progression of osteolytic lesions and to identify subgroups of patients who would benefit most from clodronate treatment. In univariate logistic regression analysis, including treatment (placebo, clodronate), sex, age, pain index, serum calcium and creatinine, myeloma stage, number of osteolytic lesions at baseline, and number of vertebral fractures at baseline as independent variables and the progression of osteolytic lesions as a dependent variable, only the treatment with a placebo was associated with the progression of osteolytic bone lesions. Separate analyses with respect to the progression of osteolytic bone lesions were carried out in the following subgroups: male v female, < or = 64 v > 64 years, stage I v stage II-III myeloma, no osteolytic lesions at baseline versus osteolytic lesions at baseline, no vertebral fractures at baseline versus vertebral fractures at baseline. and a 50% treatment response to cytotoxic drugs versus no treatment response to cytotoxic drugs. The treatment with clodronate delayed the progression of osteolytic lesions similarly in these subgroups, with the exception of a subgroup of patients who did not have a 50% treatment response to cytotoxic drugs. The treatment with clodronate did not significantly increase treatment costs. We conclude that the treatment effect of clodronate seems to be independent of sex and age of the patients, the stage of myeloma, and the severity of bone lesions at diagnosis, but not of treatment response to cytotoxic drugs. PMID- 7986714 TI - Intensive chemotherapy with blood progenitor transplantation for primary resistant multiple myeloma. AB - This study assessed the feasibility and effect of blood progenitors as the only source of haemopoietic support for myeloablative therapy for patients with primary resistant multiple myeloma and markedly infiltrated bone marrow. 17 patients with advanced, primary resistant myeloma received a priming regimen of cyclophosphamide (3 g/m2) and etoposide (900 mg/m2) with GM-CSF. During haematological recovery, at least 2 x 10(6) CD34+ mononuclear cells/kg were collected from each patient with 4-12 leukaphereses. High-dose chemotherapy was then given which consisted of thiotepa (750 mg/m2), busulfan (10 mg/kg) and cyclophosphamide (120 mg/kg) followed by reinfusion of the blood progenitors. Haemopoietic reconstitution was rapid with recovery of granulocytes to > 1.0 x 10(9)/l after a median of 10 d and of platelets to 50 x 10(9)/l after a median of 29 d. The myeloma responded in 10/17 patients for a projected median duration of at least 12 months. Survival was prolonged significantly in comparison with the outcome of control patients who did not receive intensive treatment. Blood progenitors, assessed from the number of CD34+ cells, produced early haemopoietic recovery after myeloablative therapy that induced sustained control of advanced and resistant multiple myeloma. PMID- 7986715 TI - Cellular origin and extent of clonal involvement in multiple myeloma: genetic and phenotypic studies. AB - The cellular origin and extent of clonal involvement in multiple myeloma (MM) are controversial. The third-complementarity-determining region (CDR3) of the immunoglobulin heavy chain gene is the target region of VH replacements and somatic mutations. We analysed the CDR3 sequences of myeloma cells from eight newly diagnosed and three relapsed patients in order to elucidate the target cell of malignant transformation in MM. We also examined the extent of clonal involvement in MM using a CDR3 clone-specific nucleic acid probe. The peripheral lymphocytes from the five MM patients were separated into fractions such as CD34+, CD20+CD10+, CD20+CD21+, CD20+CD19- and CD2+ cells. Amplified CDR3 DNAs from these subpopulations were hybridized with the probe specific to each patient's tumour cells. We found no evidence of ongoing VH replacements or somatic mutations in CDR3 in MM. However, frequent nucleotide mutations in D and JH segments were observed. Circulating malignant cells were detected in the CD34+ and all of the CD20+ subpopulations, but not in the CD2+ fraction. MM is a neoplasm originating from a B-lineage cell which has already undergone antigen dependent selection. Nevertheless, the tumour cells are composed of heterogeneous subpopulations at various stages of differentiation, similar to normal B-lineage cells. Conversely, T cells were not involved in MM. These results imply that there is an analogous developmental pathway between the normal B-lineage cells and the tumour cells of MM. PMID- 7986716 TI - Establishing the incidence of myelodysplastic syndrome. AB - We studied the incidence of myelodysplastic syndrome (MDS) in a population served by one district general hospital over a 10-year period (1981-90). Cases were sought through investigation of individuals presenting with suggestive peripheral blood findings. 279 new cases were diagnosed in a population rising from 203,000 to 226,000 over the study period. The observed incidence rate did not change over the study period. The crude incidence rate was 12.6/100,000/year. Age-specific incidence rates per 100,000 per year were 0.5 for age < 50, 5.3 for age 50-59, 15 for age 60-69, 49 for age 70-79, and 89 for age 80+. A cohort study of one large general practice revealed several previously unknown and asymptomatic cases, indicating that the observed figures for the population overall may still underestimate the real incidence. We conclude that MDS is more common than reported in previous studies and that incidence continues to rise into very old age. Difficulties in case ascertainment hamper reliable estimates of true incidence. PMID- 7986717 TI - The chronic myeloid leukaemias: guidelines for distinguishing chronic granulocytic, atypical chronic myeloid, and chronic myelomonocytic leukaemia. Proposals by the French-American-British Cooperative Leukaemia Group. AB - We have reviewed our experience with four of the entities that are included under the generic term chronic myeloid leukaemia (CML), namely the classic Ph+ CGL, both BCR+ and BCR-, aCML and CMML. We have developed a statistical model that confirms that CGL, aCML and CMML can be distinguished from each other with reasonable success employing five quantitative parameters (WBC, percentage immature granulocytes, percentage monocytes, percentage basophils, percentage erythroid precursors in bone marrow) and one qualitative parameter (granulocytic dysplasia). It is hoped that these detailed recommendations will enable investigators to improve their diagnostic accuracy. This should permit more uniform comparisons of molecular biologic and clinical studies. PMID- 7986718 TI - Evidence implicating calpain (Ca(2+)-dependent neutral protease) in the destructive thrombocytopenia of the Wiskott-Aldrich syndrome. AB - The Wiskott-Aldrich syndrome (WAS) is an inherited platelet/T-lymphocyte disease characterized by small platelets, thrombocytopenia and immunodeficiency. Because degradative events have a significant role, we directly examined calpain (Ca(2+) dependent neutral protease), a prominent protease in the affected cells, by functional and antigenic quantitation. Calpain activity in platelets of seven WAS patients was decreased to 59 +/- 3.7% (P < 0.01) relative to platelets of 11 normals. Platelets of two patients with immune thrombocytopenia had normal calpain activity. By immunoblotting, mu-procalpain, the mu-calpain species in resting (unstimulated) blood cells, was decreased in platelets of nine WAS patients to 58 +/- 14.6% (P < 0.01) relative to paired normals. In contrast, mu procalpain levels in lymphocytes of seven WAS patients did not differ from normal lymphocytes. Normal platelets and lymphocytes have different mechanisms for Ca(2+)-dependent mu-procalpain activation. On addition of ionophore and Ca2+ to stirred platelets, 80kD mu-procalpain was rapidly (0.5 min) and quantitatively converted to 76 kD active mu-calpain; this process was the same in WAS platelets. In lymphocytes, mu-procalpain activation was slow, only partially complete (40 min), and the active species was 78 kD. The marked depletion of calpain in WAS platelets demonstrated in this study may result from inappropriate stimulation of platelets and be related to the severe thrombocytopenia that characterizes this disease. PMID- 7986719 TI - A cross-over pharmacokinetic and thrombogenicity study of a prothrombin complex concentrate and a purified factor IX concentrate. AB - A prospective cross-over study was carried out on 19 patients with haemophilia B. comparing the pharmacokinetics of a purified factor IX concentrate prepared by metal chelate affinity chromatography (9MC) with a conventional three-factor prothrombin complex concentrate (9A). The highly purified factor IX concentrate was shown to have a half-life comparable to the PCC; the in vivo recovery of the purified concentrate was significantly greater than that of the complex (P < 0.01). The 20% change in the value of the International Standard for Factor IX Concentrate, introduced in 1988, might have been expected to lower the recovery values. However, the in vivo recovery for both concentrates was somewhat higher than reported previously, particularly in the older literature. In nine patients, serial assays for fibrinopeptide A, prothrombin fragment F1+2 and thrombin antithrombin complexes (TAT) were performed to assess the potential thrombogenicity of the two concentrates. Evidence was obtained that there was significantly less activation of coagulation following administration of purified factor IX (9MC), as compared to the activation that occurred after the PCC. PMID- 7986720 TI - Factor IX gene haplotypes in Brazilian blacks and characterization of unusual DdeI alleles. AB - Analysis of factor IX gene polymorphisms is considered the best approach for prenatal diagnosis and carrier detection of haemophilia B when the identification of the gene mutation is not possible. Studies involving factor IX gene polymorphisms in Black populations are scarce and essentially restricted to the North-American Black population whose composition is substantially different from that of the Brazilian and presumably other Black populations of South America. In this paper we report the analysis of eight factor IX gene polymorphisms in Brazilian Blacks: 5' BamHI, DdeI, intron 2 BamHI, XmnI, TaqI, TaqI, MspI, MnlI and HhaI. Characterization of the VNTR-like DdeI polymorphism revealed six different alleles: B, AB, A2B, A2B2, A3B and A5B, the last being described here for the first time. The 5' BamHI, DdeI, MspI and HhaI polymorphisms showed the highest heterozygosities (0.40-0.50) and are in linkage equilibrium with one another. 19 complete haplotypes could be identified in this population. Based on the results we propose a systematic strategy for carrier detection and prenatal diagnosis of haemophilia B in this population. The combined analysis of four polymorphisms (5' BamHI, HhaI, MspI and DdeI) provided an informative genetic marker in 85% of the females. The use of all eight polymorphisms allows information in 95% of females. Additionally, differences in gene frequencies and haplotype distribution suggest dissimilarities in factor IX gene polymorphisms between the Brazilian and the North-American Black populations. PMID- 7986721 TI - Analysis of immunoglobulin class, IgG subclass and titre of HPA-1a antibodies in alloimmunized mothers giving birth to babies with or without neonatal alloimmune thrombocytopenia. AB - We analysed the titre and isotype composition of antibodies produced by mothers giving birth to babies with or without neonatal alloimmune thrombocytopenic purpura (NAITP) and patients with post-transfusion purpura (PTP). All these individuals produced an antibody specific for the HPA-1a allotype present on the platelet glycoprotein IIb-IIIa (GPIIb-IIIa). Sera from mothers who gave birth to thrombocytopenic babies (group 1, n = 36), non-thrombocytopenic babies (group 2, n = 4) or from PTP patients (group 3, n = 3) were tested by an indirect-ELISA. Results indicated no evident differences in the isotype composition or titre of the antibodies from the three groups of sera. The antibody titre ranged from 1:120 to 1:3500. Antibodies with the IgG1 subclass were present in all sera. Most sera contained IgG1 alone (24/43 sera tested) or in combination with IgG3 (10/43). IgG2 was never present and only three sera showed intermediate reactivity with anti-IgG4 MAb. Few sera (nine sera from groups 1 and 2) were weakly positive when tested with the anti-IgM antibodies. These results suggest that neither the titre nor the isotype composition can be used to predict the severity or the occurrence of thrombocytopenia in newborns. PMID- 7986723 TI - Ten-year survival and prognostic factors in multiple myeloma. Japan Myeloma Study Group. AB - Among 1119 Japanese patients with symptomatic multiple myeloma diagnosed between 1965 and 1981, 38 (3.4%) survived more than 10 years. Younger age, low tumour mass (absence of severe anaemia, hypercalcaemia, renal failure, and multiple bone lesions), low plasma cell percentage in bone marrow, mature and intermediate myeloma according to Greipp's criteria, and a positive response to subsequent treatment, were related to long-term survival according to univariate analysis. Multivariate logistic regression analysis indicated younger age and low tumour mass as pretreatment characteristics to be related to long-term survival. Prognostic factors proposed applicable to myeloma were also related to 10-year survival. PMID- 7986722 TI - Parvovirus B19 as a cause of acquired chronic pure red cell aplasia. AB - Parvovirus B19 infection causes chronic anaemia in immunodeficient individuals by selective suppression of erythropoiesis. The bone marrow morphology is characteristic of pure red cell aplasia (PRCA). To determine the frequency of B19 induced PRCA we retrospectively analysed a series of 57 PRCA patients. B19 DNA was present in serum of eight patients (14%) and could be extracted from bone marrow aspirate slides from five of these patients. Recent exposure to the virus was confirmed by the presence of anti-B19 IgM in sera from four and by the finding of giant pronormoblasts in marrow aspirates from five of the B19 DNA positive patients. The sensitivities of anti-B19 IgM and of giant pronormoblasts were only 50% and 63%, respectively; specificities were 90% and 92%. Unexpectedly, PRCA in two B19 DNA-positive patients remitted after antilymphocyte globulin or cyclosporin A therapy, suggesting that the clinical course of B19 induced PRCA may be indistinguishable from other forms of PRCA. As therapy with immunoglobulin is uniformly effective for treatment of B19-associated anaemia, our data suggest that all patients with acquired PRCA should be evaluated for evidence of B19 infection. B19 DNA analysis is the most reliable method to demonstrate infection. PMID- 7986724 TI - Unexpected remission of acute myeloid leukaemia after GM-CSF. AB - The administration of granulocyte-monocyte colony-stimulating factor (GM-CSF) was associated with complete clinical and haematological response in an adult patient with minimally differentiated acute myeloid leukaemia who presented with pneumonia and moderate neutropenia, but no blast cells in the peripheral blood. The response lasted 9 months. At relapse, a second GM-CSF course resulted in a very good partial remission lasting 5 months, although differences in the kinetics of haemoglobin, neutrophil and platelet recovery were noted. Subsequent recurrences were managed with chemotherapy, a complete remission being obtained twice more and lastly consolidated with myeloablative chemo-radiotherapy supported by a peripheral blood stem cell autograft. This report suggests that GM CSF should be further investigated as a therapeutic agent in selected cases of AML. PMID- 7986725 TI - Detection of trisomy 12 in chronic lymphocytic leukaemia: comparison of a polymerase chain reaction based technique with fluorescence in situ hybridization. AB - Trisomy 12 is the most frequent chromosomal aberration in chronic lymphocytic leukaemia (CLL) and seems to indicate a poor prognosis. To detect this abnormality we tested the applicability of the polymerase chain reaction (PCR) and compared it to the current standard fluorescence in situ hybridization (FISH). Two DNA regions containing variable numbers of tandem repeats (VNTR) located on (a) the long and (b) the short arm of chromosome 12 were chosen for PCR analysis. 8/72 patients (11%) were trisomy 12 positive compared to 16% by FISH. Chromosomal imbalances were only detected by PCR if at least 20% of the cells carried the numerical aberration. PMID- 7986726 TI - Familial discrepancy between the one-stage and two-stage factor VIII methods in a subgroup of patients with haemophilia A. AB - A higher result for plasma factor VIII:C measured by the one-stage as compared with the two-stage method has been described in some patients with haemophilia A or with von Willebrand's disorder. We used both methods to measure FVIII:C in 95 patients with haemophilia A. The results were equivalent in all 21 patients with severe haemophilia (16 families) and in 45 of the patients with mild or moderate haemophilia (18 families). However, the results were discrepant (FVIII:C by one stage assay 2-7-fold higher than by two-stage assay) in the other 29 patients with mild or moderate haemophilia (12 other families). For each patient with discrepant FVIII:C results the classification was the same for all other affected members of his family. In some families with haemophilia A the gene defect leads to a discrepancy between the one-stage and two-stage FVIII:C results and may be more widespread than previously recognized. PMID- 7986727 TI - Dose of desferrioxamine and evolution of HIV-1 infection in thalassaemic patients. AB - To study the relationship between the dose of desferrioxamine (DFX) and the progression of the HIV-1 disease in thalassaemia major patients (TMP), 64 seropositive TMP patients were studied. Cumulative incidence of CDC stage IV was calculated using a non-parametric life-table method. The association with the mean daily dose of DFX was tested with a Cox proportional hazards model which was also used to adjust for confounding variables. The median of the mean daily dose of DFX over the seropositive period was 40 mg/kg (range 0-65 mg/kg). Age at seroconversion (P < 0.02) and splenectomy (P < 0.03) were found to be associated with the mean daily dose of DFX. 6.5 years after seroconversion, 11% of those who had been prescribed more than 40 mg/kg of DFX daily had entered stage IV versus 35% of those who had been prescribed a lower dose (P < 0.01). When the dose was taken as a continuous variable it was found that the rate of progression was significantly smaller in TMP receiving a higher dose (P < 0.002), even after adjusting for age and splenectomy (P < 0.02). Although it should be noted that these results were obtained in an observational study, possibly biased by a non random allocation of the DFX dose, we believe that they are striking enough to support the claim that the role of DFX in the progression of HIV disease should be further evaluated. PMID- 7986728 TI - Adult T-cell leukaemia with various abnormalities in endocrine and metabolic systems. AB - Adult T-cell leukaemia (ATL) is a unique type of T-cell malignancy closely associated with human T-cell leukaemia virus-1 (HTLV-1). Despite frequent descriptions of hypercalcaemia, cases accompanied by diabetes insipidus or syndrome of inappropriate secretion of anti-diuretic hormone (SIADH) in ATL patients have rarely been reported. We present an unusual case of ATL with various abnormalities in his endocrine and metabolic systems involving anterior pituitary function, thyroid function, lipid metabolism and Ca metabolism. Some of these abnormalities were considered to arise from infiltration or leukaemic cells into systemic organs after elimination of the above symptoms. Clinical and haematological data showing improvement following chemotherapy are also presented. PMID- 7986729 TI - Hypercalcaemia in B cell chronic lymphocytic leukaemia. AB - Hypercalcaemia is common in some lymphoproliferative disorders such as myeloma or T-cell leukaemia-lymphoma, but is rarely described in B cell chronic lymphocytic leukaemia (BCLL). We report the case of a patient with BCLL, hypercalcaemia and osteolytic bone lesions. Parathyroid hormone-related protein (PTHrP) mRNA was identified by Northern blot analysis of liver, spleen and lymph node tumour samples. Serum levels of tumour necrosis factor alpha (TNF alpha) were increased. PMID- 7986730 TI - Acquired sideroblastic anaemia following progesterone therapy. AB - We report a case of acquired sideroblastic anaemia precipitated by progesterone. On two separate occasions, over 15 years apart, the patient developed sideroblastic anaemia with iron overload shortly after the administration of progesterone. No other cause for sideroblastic anaemia was found, and treatment with folic acid, pyridoxine or androgens corrected the anaemia. In both instances removal of the progestational agent led to prompt disappearance of the anaemia as well as the ringed sideroblasts. Using a two-phase liquid culture procedure in which human peripheral blood-derived progenitor cells undergo erythroid proliferation and differentiation, we demonstrated enhanced sensitivity of the patient's erythroid progenitors to progesterone. We conclude that progesterone should be added to the list of medications known to be associated with acquired sideroblastic anaemia. PMID- 7986731 TI - Mutations in the PIG-A gene causing partial deficiency of GPI-linked surface proteins (PNH II) in patients with paroxysmal nocturnal haemoglobinuria. AB - Paroxysmal nocturnal haemoglobinuria (PNH) is due to the absence or marked reduction of glycan phosphatidylinositol (GPI)-anchored proteins on the surface of blood cells. Affected patients may have a population of red blood cells that are completely deficient (PNH III) or partially deficient (PNH II) in these proteins, or they may have both. PNH III has recently been shown to be due, in all cases examined, to a somatic mutation in the PIG-A gene, whose product is required for an early step in GPI anchor synthesis. We now show that two patients with PNH II cells also have somatic mutations of the same gene: these produce a partial rather than a total loss of PIG-A function. PMID- 7986732 TI - Restoration of normal polyclonal haemopoiesis in patients with chronic myeloid leukaemia autografted with Ph-negative peripheral stem cells. AB - Only a minority of patients with chronic myeloid leukaemia (CML) benefit from allogeneic bone marrow transplantation (BMT), a potentially curative therapy, or from treatment with interferon alpha, which prolongs survival in cytogenetic responders. In Genoa a programme has been initiated in which CML patients are autografted with Ph-negative peripheral stem cells. To assess the pattern of marrow reconstitution, we studied the clonality of haemopoiesis in five females who engrafted and were Philadelphia chromosome negative. This was performed by evaluating the methylation patterns of the X-linked hypervariable DXS255 locus with the probe M27 beta. All four analysable women showed polyclonal methylation patterns in both granulocytes and T lymphocytes, suggesting that marrow reconstitution occurred from normal residual stem cells. PMID- 7986733 TI - GM-CSF in the treatment of Fanconi's anaemia. AB - We have used recombinant human (rh) GM-CSF in two 12-year-old Fanconi's aplastic anaemia patients. They had not received any previous therapy except blood transfusions. Each patient was given three 21 d courses of rh-GM-CSF, the first two at a dose of 3.5 micrograms/kg/d and the third at 7 micrograms/kg/d s.c. There were significant increases in WBC and absolute neutrophil counts after the first week of rh-GM-CSF which lasted as long as the treatment was continued. Following the cessation of treatment, WBC and ANC dropped rapidly. We conclude that rh-GM-CSF can be used in FAA, especially in severely neutropenic cases. PMID- 7986734 TI - Familial thrombophilia and activated protein C resistance: thrombotic risk in pregnancy? AB - An abnormal anticoagulant response in vitro to activated protein C (aPC) has been proposed as an aetiological factor in familial thrombophilia. It is postulated that this phenomenon is due to an inherited molecular defect of factor V resulting in poor inactivation by aPC. We conducted a family study when the proband presented in her second pregnancy with superficial phlebitis, a history of deep venous thrombosis and a family history of venous thromboembolic disease. No abnormality of antithrombin activity, protein C activity or deficiency of protein S were demonstrated in the family members tested. The proband had aPC ratios below the laboratory range on three consecutive occasions. In addition, her mother, who had a history of recurrent DVTs and a pulmonary embolus, and also an asymptomatic nulliparous sister, both had aPC resistance ratios below the laboratory range on consecutive samples. Further information about the combined risk of aPC resistance and pregnancy is needed before guidance on the management of affected women can be formulated. PMID- 7986735 TI - IL-6 might relieve long-standing thrombocytopenia in autotransplanted AML patients. PMID- 7986736 TI - Idiopathic myelofibrosis: anaemia may respond to low-dose dexamethasone. PMID- 7986737 TI - Spontaneous remission in acute myeloid leukaemia: a role for endogenous production of tumour necrosis factor and interleukin-2? PMID- 7986738 TI - Spontaneous remission in acute myeloid leukaemia. PMID- 7986739 TI - Lineage involvement in chronic myeloproliferative disorders. PMID- 7986741 TI - Subcutaneous palisading granuloma of the scalp in childhood. AB - Subcutaneous palisading granulomas, lesions characterized by collagen necrosis and chronic inflammatory changes, may present as ill-defined, immobile, nontender masses of the scalp. They are frequently multiple and may vary in size over time. Imaging studies rarely show involvement of the calvarium. The histological pattern of palisading histiocytes around necrobiotic granulomas is seen in association with a variety of systemic illnesses but more commonly occurs as an isolated entity in childhood. They are unlikely to herald rheumatological disease unless the erythrocyte sedimentation rate is elevated. In the presence of juvenile rheumatoid arthritis, histological confirmation is usually not indicated. If the lesions are not associated with any other clinical symptoms excisional biopsy may be indicated to establish a diagnosis. The nodules need not be removed as they will spontaneously regress. PMID- 7986740 TI - Immunoreactive interleukin-6 and C-reactive protein in plasma cell disorders. PMID- 7986742 TI - Exciting your neurons to death: can we prevent cell loss after brain injury? AB - During the past 10-15 years, major advances have been made in understanding the pathophysiologic events that occur following central nervous system insults. It has become clear that a variety of insults have in common their ability to initiate a complex cascade of biochemical events at the cellular level which, over time, lead to neuronal death. Because these events take time to occur, interruption of these cascades offers the hope of specific neuron-salvaging therapy, even when given after the insult, and provides a major step forward from conventional supportive care. This paper reviews these principles as they relate to traumatic brain injury, with emphasis on excitatory amino acid neurotransmitter toxicity (excitotoxicity). Preliminary results in animal experiments and in severely head-injured children are discussed. PMID- 7986744 TI - A critical review of personal experiences with craniopharyngioma: clinical history, surgical technique and operative results. 1983. PMID- 7986743 TI - Cardiopulmonary bypass, hypothermic circulatory arrest and barbiturate cerebral protection for the treatment of giant vertebrobasilar aneurysms in children. AB - Intracranial aneurysms in the pediatric population are rare lesions with a significant proportion occurring as giant aneurysms involving the vertebrobasilar system. The complex anatomy of these lesions frequently creates an extremely difficult management dilemma. We present two patients, a 9-year-old and a 13-year old, with giant fusiform vertebrobasilar aneurysms, to illustrate the utility of cardiopulmonary bypass, hypothermic circulatory arrest and barbiturate cerebral protection for successful surgical treatment of these complex intracranial vascular lesions in children. PMID- 7986745 TI - Inhibition of cell growth by TGF beta 1 is associated with inhibition of B-myb and cyclin A in both BALB/MK and Mv1Lu cells. AB - The concept of positive and negative regulation of normal cellular growth by diffusible factors is well illustrated by the effects of epidermal growth factor and transforming growth factor beta 1 (TGF beta 1) on mouse keratinocytes (MK) and mink lung epithelial cells (Mv1Lu). MK and Mv1Lu are nontransformed cell lines that reversibly arrest at a point in late G1 in response to TGF beta 1. Previously, we have shown that expression of the protooncogene c-myc is induced upon epidermal growth factor stimulation of quiescent MK and Mv1Lu cells and that transcriptional suppression of c-myc by TGF beta 1 treatment is important in the TGF beta 1 growth inhibition pathway. Using epidermal growth factor-stimulated synchronized MK and Mv1Lu cells, we have investigated the mRNA expression of a large number of growth factor-inducible genes that are critical regulators of growth in G1 and at the G1/S transition. These genes, often found to be dysregulated in cancer, include transcription factors as well as cyclins and their associated kinases, that promote growth, and tumor suppressor genes, that inhibit growth. As reported here, TGF beta 1 significantly inhibited mRNA expression of B-myb and cyclin A in both cell lines, suggesting that these may be important common downstream targets in the growth inhibition pathway. In contrast, the expression patterns of cyclins D1 and D2 and the transcription factors E2F1 and E2F2 were unaffected in MK cells treated with TGF beta 1 but were significantly inhibited in TGF beta 1-treated Mv1Lu cells. We cite the evidence suggesting that the inhibition of B-myb and cyclin A may contribute to the late G1 arrest caused by TGF beta 1 and that these events may be linked through the actions of the product of the retinoblastoma susceptibility gene (Rb) or an Rb family member. PMID- 7986746 TI - Induction of epidermal growth factor receptor gene transcription by transforming growth factor beta 1: association with loss of protein binding to a negative regulatory element. AB - Transforming growth factor beta (TGF-beta) is a potent modulator of cell growth in many systems. In normal rat kidney fibroblasts, TGF-beta 1 increases epidermal growth factor (EGF) receptor gene transcription and synergizes with EGF to stimulate growth in soft agar, a characteristic of the transformed phenotype. In order to identify the target of TGF-beta 1 action, we have used a series of 5' deletion mutants of the EGF receptor promoter linked to a chloramphenicol acetyltransferase reporter gene (ERCAT). The TGF-beta response element(s) was localized to a cis-regulatory region which resides between positions -919 and 860 relative to the ATG translation initiation codon of the EGF receptor promoter. This 60-base pair region contains a repressor of the EGF receptor promoter and a TGF-beta inhibitory element that mediates TGF-beta 1 suppression of transin/stromelysin gene transcription through binding of a Fos-containing protein complex. Cotransfection of c-fos, c-jun, or both expression vectors with the intact or 5'-deleted ERCAT constructs identified several Fos-responsive inhibitory regions within the EGF receptor promoter, but these did not localize to the -919 to -860 promoter region. Mobility shift assays showed binding of the 60-base pair DNA fragment to proteins in extracts from untreated normal rat kidney cells; the binding was specifically competed by oligonucleotides containing a CAGATG sequence but not by oligonucleotides containing the EGF receptor repressor or the TGF-beta inhibitory element. TGF-beta 1 treatment but not anti-Fos antibody caused a decrease in specific 60-base pair DNA-protein complex formation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7986747 TI - Metallopanstimulin gene product produced in a baculovirus expression system is a nuclear phosphoprotein that binds to DNA. AB - The protein product of the human Metallopanstimulin (MPS-1) gene was produced in the insect cell line Spodoptera frugiperda (Sf9) using the baculovirus expression vector system Autographa californica nuclear polyhedrosis virus (AcNPV). When a cloned MPS-1 complementary DNA sequence was inserted into the AcNPV viral genome downstream from the promoter of the polyhedrin gene, a polypeptide with an apparent molecular weight of approximately 10,000 was observed in extracts of infected Sf9 cells. This protein was not detected in Sf9 cells infected with AcNPV-MPS-1-Del, a vector in which the MPS-1 gene was deleted. The MPS-1 protein was produced at high levels in this host-vector system (congruent to 12% of total labeled soluble protein). Characterization of the MPS-1 protein extracted from Sf9 infected cells showed that it: binds zinc ions specifically; is phosphorylated; accumulates in the nucleus; is tightly bound to the nucleus; and binds to calf thymus DNA-cellulose. The MPS-1 protein constitutes one of the major proteins in the nuclear fraction of Sf9 cells and can be purified from this source to near homogeneity by a two-step procedure composed of high-performance liquid chromatography and gel electrophoresis. Antibodies were raised against selected peptide sequences of the MPS-1 protein and used to detect MPS-1 in insect cells and in various cultured mammalian cell types. Western analysis demonstrated that the baculovirus-generated protein had electrophoretic and immunological properties equivalent to those of MPS-1 spontaneously expressed in various human mammalian cell lines. Finally, recombinant MPS-1 generated a specific protein-DNA complex with a duplex oligomer containing a cyclic AMP responsive element, as assessed by gel mobility shift assays. These results support the hypothesis that the MPS-1 protein may act, at least in part, by interacting with genes possessing the cyclic AMP-responsive element sequence. PMID- 7986748 TI - Regulation of vimentin gene transcription in human breast cancer cell lines. AB - We have investigated the control of vimentin expression in human breast cancer cell lines because of its transcriptional activation during malignant progression in breast cancer. Comparison of vimentin-positive (V+) and vimentin-negative (V-) breast cancer cell lines revealed several potential areas of vimentin gene regulation. Analysis of the chromatin structure of the vimentin gene in V+ and V- breast cancer cells showed DNase I hypersensitive sites in the 5' promoter region in V+ cell lines and 3' to the start of transcription in V- cell lines. Promoter deletion and reporter gene analysis revealed the importance of two adjacent AP-1 sites separated by seven GC-rich nucleotides for vimentin expression in V+ breast cancer cells. Mutational analysis of these sequences showed that although both AP 1 sites could bind nuclear proteins from V+ cells in vitro, one AP-1 site was sufficient to drive transcription in CAT reporter gene assays. The GC-rich spacer region had a modulating function on the activity of the AP-1 sites. In addition, levels of c-jun mRNA were elevated in V+ versus V- cells. In summary, distinct sites within the vimentin gene appear to be important for the control of vimentin expression in V+ and V- breast cancer cells with multiple elements acting coordinately to regulate vimentin expression. PMID- 7986749 TI - Regulation of murine Max (Myn) parallels the regulation of c-Myc in differentiating murine erythroleukemia cells. AB - Max is a basic region-helix-loop-helix-leucine zipper protein that consists of two major isoforms, p22 (long form, Max-L) and p21 (short form, Max-S). These proteins are encoded by two [the 1.9- and the predominant 2.3-kilobase (kb) forms] of the five alternatively spliced max mRNA species. We now demonstrate that N,N'-hexamethylene bisacetamide-mediated differentiation of murine erythroleukemia cells leads to a pattern of biphasic down-regulation of the 1.9- and the 2.3-kb myn (murine max) mRNAs that closely parallels that which occurs for myc mRNA. In contrast, the p22/Myn-L and p21/Myn-S protein isoforms down regulate in monophasic fashion. Unlike the short-lived myc mRNA, the myn message is quite stable. However, its half-life of 3-6 h is still consistent with the biphasic down-regulation that accompanies differentiation. Furthermore, unlike myc, the overexpression of which prevents differentiation, elevated max levels merely delay differentiation. Coincident with this is a delay in the second decline of c-myc mRNA. In N,N'-hexamethylene bisacetamide-induced cells blocked from differentiating by overexpression of c-, N- or L-myc, myn mRNA expression is constitutive. These findings suggest that myn may also be involved in differentiation. PMID- 7986750 TI - An endogenous signal triggering erythroid differentiation: identification as thyroid hormone. AB - The identification of thyroid hormone as an endogenous signal for erythroid differentiation began with our studies on the spontaneously differentiating murine erythroleukemia clone 3-1. We observed that the spontaneous differentiation frequency was dependent on a heat stable factor present in fetal calf serum or calf bone marrow. We also noted that the bone marrow extract stimulated erythroid colony-forming units in mouse bone marrow cells, suggesting the relevance of this factor in normal erythroid differentiation. The bone marrow extract did not supplant the requirement of erythropoietin but was synergistic. Purification of the bone marrow extract indicated that the differentiation inducing activity for clone 3-1 cells cochromatographed with a low-molecular weight, UV (280 nm)-absorbing component(s). These observations and previous reports identifying the avian erythroblastosis virus oncogene v-erbA as a mutated thyroid hormone receptor which blocked erythroid differentiation led us to test thyroid hormone in our assay. Both triiodothyronine and thyroxine were highly active, and the active constituents in the chromatographically purified fraction were identified as triiodothyronine and thyroxine. Although thyroid hormone action has been associated with both in vivo and in vitro erythroid differentiation, its role has been often relegated to a secondary status. We suggest that thyroid hormone is required for the commitment of erythroid cells to terminal differentiation. PMID- 7986751 TI - Avian myeloblastic cell lines transformed by two nuclear oncoproteins, P135gag myb-ets and p61/63myc: a model of retinoic acid-induced differentiation not abrogated by v-erbA. AB - We previously demonstrated that the retroviral construct MHE226 transducing both the P135gag-myb-ets and p61/63myc nuclear proteins induces solid hemopoietic tumors in early chicken embryos. In the present paper, we report the characterization of two MHE226-transformed cell lines established from such hemopoietic tumors retrieved from the heart of a 13-day embryo. Cytological analysis indicated a myeloblastic phenotype. These MHE226 cell lines were positive for the MEP17 monoclonal antibody but were negative for the myeloblast specific 51/2 monoclonal antibody. MHE226 cell lines displayed a doubling time of about 20-24 h and were maintained for at least 1 year. Contrary to E26 myeloblastic cell lines, MHE226 cell lines were independent of chicken myelomonocytic growth factor and could be maintained in serum-free medium. MHE226 cell lines could be induced to differentiate toward the monocytic lineage by retinoic acid. Retinoic acid inhibited proliferation of MHE226 cell lines as early as day 1. After 3 days, MHE226 cells displayed cytological, enzymatic (alpha-naphthyl acetate esterase and chloroacetate esterase), and functional (phagocytosis) characteristics of monocytic cells. The retinoic acid-induced differentiation of MHE226 cells could not be inhibited by v-erbA. Thus, MHE226 transformed cell lines represent a novel model of cell transformation by two nuclear oncoproteins. Furthermore, they provide a model to study molecular mechanisms implicated in the monocytic differentiation program. PMID- 7986752 TI - Distinct responses of protein kinase C isozymes to c-erbB-2 activation in SKBR-3 human breast carcinoma cells. AB - We have studied the effect of activation of the c-erbB-2 receptor tyrosine kinase on protein kinase C (PKC) in cultured SKBR-3 human breast cancer cells. Treatment with the agonistic anti-receptor monoclonal antibody TAb 250 induces receptor autophosphorylation and stimulates phospholipase C-gamma 1 (L. K. Shawver et al. Cancer Res., 54: 1367-1373, 1994). TAb 250 induced a rapid and marked translocation of PKC histone phosphorylation activity to the particulate fraction of SKBR-3 cells. By immunoblot, however, this translocation was limited to specific PKC isozymes. beta PKC and zeta PKC translocated to the particulate fraction, whereas epsilon PKC underwent "partial reversed translocation" to the cell soluble fraction after receptor stimulation. Furthermore, beta PKC was rapidly degraded following TAb 250 treatment. By immunocytochemistry, beta IPKC translocated from the perinuclear area to the cytosol and into the nucleus, whereas zeta PKC translocated to the perinuclear region and into the nucleus. Consistent with the Western blot results, epsilon PKC translocated from the nucleus to the perinuclear area and the cytosol. These changes in the localization of PKC isozymes were not observed after addition of normal IgG1 or a nonagonistic anti-c-erbB-2 monoclonal antibody to SKBR-3 cells. alpha, beta II, or delta PKC present in these cells did not translocate following receptor stimulation. These data indicate that c-erbB-2 signal transduction may involve the activation of specific PKC isozymes. The biological role of these enzymes in the phenotype and cellular responses of c-erbB-2-overexpressing carcinoma cells remains to be studied. PMID- 7986753 TI - Protein kinase C isozyme expression and down-modulation in growing, quiescent, and transformed renal proximal tubule epithelial cells. AB - Renal alpha-protein kinase C (PKC) is rapidly down-modulated modulated in animals treated with the renal toxin and tumor promoter, folic acid (Dong et al., Cancer Res., 53: 4542-4549, 1993). To further explore the role of PKC isozymes in renal growth and carcinogenesis, we compared phorbol ester receptor and PKC isozyme content, distribution, and regulation in primary and oncogene-altered rat renal proximal tubule epithelial cells (RPTE) in culture. Immunoblot analysis and RNase protection assays indicated that RPTE expressed at least four PKC isozymes, alpha, delta, epsilon, and zeta. Total phorbol ester receptors were decreased in primary proliferating, E1A-immortalized, and SV40-transformed RPTE compared to primary quiescent RPTE. The decrease in PDBu binding was largely due to a specific decrease in alpha-PKC protein content to approximately 50% of the level in quiescent RPTE. Degradation rates and message levels were compared to determine the mechanism for the decrease in alpha-PKC. Whereas alpha-PKC message levels in quiescent and proliferating primary RPTE were comparable, alpha-PKC degradation was increased in proliferating cells. These results indicate that the decreased alpha-PKC content was due largely to increased turnover. Phorbol ester stimulated the rate of degradation, thus demonstrating a link between degradation rate and PKC activation. These results suggest that the increased basal degradation rate in proliferating and oncogene-altered cells reflects an increase in activity of PKC in these cells. PMID- 7986754 TI - Potential role for focal adhesion kinase in migrating and proliferating keratinocytes near epidermal wounds and in culture. AB - In normal, differentiating skin, hemidesmosomes make the stable attachment of basal epidermal keratinocytes to the dermis by linking the cytoplasmic keratin intermediate filaments to components of the basal lamina. In contrast, laterally migrating and proliferating basal keratinocytes in culture and presumably in repairing wounds use focal adhesions to form dynamic attachments to the dermis by linking actin microfilaments to the extracellular matrix. Focal adhesion kinase (FAK), a non-receptor protein tyrosine kinase concentrated along with phosphotyrosine-containing proteins in the focal adhesions of some cultured cells, is activated in vitro when cells attach, form focal adhesions, and spread. This report finds that FAK is activated, as determined from its increased phosphotyrosine content and from its increased labeling with [gamma-32P]ATP, in immunoprecipitates from human cultured keratinocytes attached and spreading on fibronectin compared to those attached but not spreading on polylysine. Furthermore, immunofluorescence shows that both FAK and phosphotyrosine are concentrated in the focal adhesions of cultured keratinocytes attached and spreading on extracellular matrix components known to facilitate cellular migration (fibronectin, collagens I or IV, and epiligrin). Finally, immunohistochemistry localizes FAK to the epidermal-dermal junction in repairing partial thickness burn wounds. FAK is found at the epidermal-dermal junction at sites and times which coincide with actively migrating or rapidly proliferating basal keratinocytes, suggesting that this distribution represents FAK concentrated and activated in adhesions analogous to the focal adhesions seen in cultured cells. Hence, FAK appears to have an important in vivo role in the reepithelialization of human wounds. PMID- 7986756 TI - The UKCCCR adjuvant breast cancer (ABC) trial. ABC Trial Steering Committee. PMID- 7986755 TI - Regulation of thymidine kinase protein stability in serum-stimulated cells. AB - The mechanism of posttranscriptional regulation of thymidine kinase (TK) enzyme levels following serum stimulation of quiescent cells has been investigated using stably transfected Rat 3 (TK-) cells containing the human TK complementary DNA linked to a hybrid SV40/human TK promoter. These cells expressed a wild-type human TK mRNA at relatively constant levels during the first G1 and S phase after serum stimulation. In contrast, TK enzyme activity and protein levels were low during G1 and increased dramatically as the cells entered S. A comparison of the patterns of protein expression (by Western blot) and enzyme activity indicated that the specific activity of the protein did not vary between G1 and S. A combination of pulse labeling and pulse-chase experiments indicated that the increase in TK protein levels at the G1-S transition was primarily the result of a stabilization of the protein at that time. The stability of a mutant form of TK lacking 16 NH2-terminal amino acids was regulated similarly to the wild-type, indicating that this region of the protein is not required for the regulation of protein turnover. Finally, indirect immunofluorescent labeling demonstrated that TK is uniformly distributed in the cytoplasm during both G1 and S phase. PMID- 7986758 TI - Are you keeping up to date? Continuing Medical Education for oncologists. PMID- 7986757 TI - Pacemakers in radiotherapy. PMID- 7986759 TI - Chemotherapy for germ cell tumours: prophylactic ciprofloxacin reduces the incidence of neutropenic fever. AB - To assess the value of prophylactic ciprofloxacin in reducing the incidence of neutropenic fever in men receiving intensive chemotherapy for germ cell tumours, we reviewed the case notes of 88 consecutive patients treated between January 1986 and December 1992. Nadir blood counts were performed in all patients on day 14. From 1989, prophylactic ciprofloxacin 250 mg b.d. was started when the neutrophil count was less than 1 x 10(9)/l and then prescribed for all subsequent courses of chemotherapy from day 7 to day 21. In total, 88 men received 429 courses of chemotherapy. Prophylactic ciprofloxacin was prescribed for 168 courses. This was associated with a trend towards reducing the risk of admission per course of chemotherapy from 8% (20/261) to 4% (6/168) (P = 0.08). WHO grade 3/4 neutropenia (< 1 x 10(9)/l) was documented for 240 (56%) courses of chemotherapy. The incidence of fever in these patients was significantly reduced from 15% (20/131) to 5% (6/109) (P = 0.02) with prophylactic ciprofloxacin. Two patients, one of whom had received prophylactic ciprofloxacin, died of chest infection confirmed on post-mortem. The results of this non-randomized, retrospective study suggest that prophylactic ciprofloxacin 250 mg b.d. is effective in reducing the incidence of fever complicating neutropenia during chemotherapy for germ cell tumours. To be cost effective, it should be given only to neutropenic patients. PMID- 7986760 TI - A computerized data collection system for a cancer centre. AB - A data system has been designed for a cancer centre and, with the close collaboration of staff, has been brought into use. Data are continuously gathered by doctors, nurses, radiographers and cancer registration staff for the contracting process, cancer registration, audit, research and development. PMID- 7986762 TI - Preliminary clinical performance of a scanning detector for rapid portal imaging. AB - A scanning megavoltage imaging detector, with associated image storage and analysis facilities has been developed. This produces images of the treatment portals in under 10 seconds, in a digital format, facilitating rapid, quantitative image analysis. Image quality is comparable to, and at some sites improves upon, that available from film. Clinical problems in the use of megavoltage imaging include limited field of view, loss of information at the field edge due to penumbra effects, degradation of the image by bowel gas, and difficulties in the detection of soft tissue-air interfaces. Possible solutions to these problems are discussed. The imaging system has been used to assess the random errors occurring during routine para-aortic nodal irradiation. The errors detected are small, with over 95% of set-ups lying within +/- 4.5 mm of the mean daily position. No differences were detected in the magnitude of random errors between anterior and posterior treatment fields. PMID- 7986761 TI - A randomized study of telephone contact following completion of radiotherapy. AB - The hypothesis tested was that routine contact by telephone might significantly improve the adequacy of support for patients during the potentially stressful period between completing radiotherapy and the first follow-up visit. The study was a randomized controlled trial in which 100 patients were allocated either to telephone contact (intervention arm) or usual care (control arm). Adequacy of support was assessed by a questionnaire administered at the first follow-up visit. There were no significant differences in the perceived adequacy of support between the two arms. Of the 72 patients who completed questionnaires, 76% of those in the intervention arm versus 61% in the control arm rated their support after radiotherapy as 'extremely adequate'. The 95% confidence interval (CI) for this 15% rate difference was -6- +36. Analysis by intention to treat showed a rate difference of only 4% (95% CI -17-(+)25) in favour of intervention. We conclude that, given the limited resources currently available, it is not possible to justify a policy of routine contact by telephone for all patients completing radiotherapy. PMID- 7986763 TI - Success and failure in screening for cervical cancer. PMID- 7986764 TI - Population and Bayesian pharmacokinetics in oncology. PMID- 7986765 TI - European Society of Mastology Consensus Conference on Breast Cancer screening, Paris, 4-5 February 1993: report of the Evaluation Committee. PMID- 7986766 TI - Sarcoma of the prostate treated with radiotherapy. AB - Sarcoma of the prostate is a rare primary tumour in adults. We report a 73-year old man who presented with urinary outflow obstruction. He had histologically proven prostatic sarcoma and probably derived some benefit from radiotherapy. A brief review of the literature is included. PMID- 7986768 TI - Explicit memory, repetition priming and cognitive skill learning in schizophrenia. AB - Explicit memory and two forms of implicit memory, repetition priming and cognitive skill learning, were examined in twenty-four schizophrenic patients and twenty-four normal control subjects previously matched for sex, age, and educational level. Two explicit tasks, free recall and frequency monitoring, and two implicit tasks, word completion and the Tower of Toronto puzzle, a variant of the Tower of Hanoi puzzle, were selected. The performance of schizophrenic patients was impaired in both explicit tasks, whereas repetition priming was intact; in the Tower of Toronto puzzle, a deficit was observed in problem solving, but not in skill learning. This dissociation between explicit and implicit memory is not entirely consistent with the hypothesis of a deficiency in effort-demanding information processing. It could be better accommodated by a model of a disturbance in the internal representation of context. PMID- 7986767 TI - Sustained attention and positive formal thought disorder in schizophrenia. AB - Deficits in sustained attention and formal thought disorder (FTD) are two characteristics of schizophrenia that might be expressions of a common pathology. This study examined whether a measure of enduring (post-treatment, stabilized) deficits in sustained attention, the Continuous Performance Test (CPT) could predict FTD. In addition, a comparison was made of CPT performance between subjects with schizophrenia (n = 41) and healthy controls (n = 28). Results replicated previous findings of significantly poorer performance by individuals with schizophrenia compared to normal controls. Within the schizophrenia group, significant correlations were found between FTD and CPT measures. In order to assess predictability of FTD, a hierarchical multiple regression analysis was used. CPT errors and gender both significantly predicted FTD. The most robust prediction was of residual FTD (post-treatment, stabilized) by CPT commission errors. These results lend support to the proposition that a subsyndrome within schizophrenia exists that is characterized by deficits in sustained attention and positive formal thought disorder. Furthermore, this subsyndrome might be more common in males than females. PMID- 7986769 TI - Performance on tests of diencephalic-hippocampal verbal memory function in schizophrenia, Korsakoff's syndrome and personality disorder. AB - Performance on selected scores from the California Verbal Learning Test (CVLT) was compared in schizophrenia, Korsakoff's syndrome, and personality disorder patients. Five CVLT scores sensitive to dysfunction in the diencephalic hippocampal memory system and one attention-sensitive variable were examined. The patient groups were matched on age, education, and verbal ability (WAIS-R). Schizophrenia patients differed consistently from Korsakoff patients on diencephalic-hippocampal memory variables. However, they did not differ significantly from patients with personality disorders. The three groups were comparable on immediate memory. Results are discussed in terms of the nature of memory problems in schizophrenia and the extent to which these problems reflect dysfunctional subcortical processing. PMID- 7986770 TI - Effects of clozapine, fluphenazine, and placebo on reaction time measures of attention and sensory dominance in schizophrenia. AB - Two reaction time (RT) paradigms were used to study clozapine's effects on sustained and selective attention compared to fluphenazine and placebo in 25 chronic schizophrenic patients. Sensory dominance was studied via simple and choice RTs to lights and tones, and on double-stimulus trials in which the two stimuli were presented simultaneously. Although 8 of the 25 patients could not perform the RT tasks when taking placebo, there were no effects of clozapine on simple or choice RT compared to placebo or fluphenazine. Subjects on all 3 treatments showed visual dominance: faster RT to lights than to tones on choice and double-stimulus trials. However, clozapine reduced this by means of a selective increase in RT to lights. Clozapine reduced failures to respond to the tone on double-stimulus trials. This was shown to be due to reductions in hallucinations. Clozapine does not generally improve attention, but it may increase the ability of schizophrenic persons to process nondominant or unattended stimuli possibly by increasing the efficiency of resource allocation. This may be partially mediated by a reduction in hallucinations. PMID- 7986771 TI - Functional influence of the central noradrenergic system on the skin conductance activity in rats. AB - Pharmacological studies on neuroleptics and amphetamine strongly suggest that some dysfunction of the central catecholamine system may play a key role in the pathogenesis of schizophrenia. Our previous studies have demonstrated that intraventricular administration of 6-hydroxydopamine, a selective neurotoxin of the catecholamine neuron, can reproduce schizophrenia-like abnormalities in the skin conductance activity. In the present experiments, effects of pharmacological modulation of the central noradrenergic activity were studied in rats. Stimulation of the central noradrenergic activity by yohimbine (0.6 mg/kg, i.m.) slowed down the habituation of the skin conductance response (SCR) and increase the spontaneous fluctuation of the skin conductance (SF), while inhibition of the activity by clonidine (0.06 mg/kg, i.m.) accelerated or obliterated the SCR and decreased the SF frequency. If the functional significance of the central noradrenergic system lies in vigilance control, the present results are consistent with classical theory in psychophysiology: the habituation rate of SCR and the frequency of SF are correlated well with each other and both indices reflect arousal level. The disorder of the system should produce not only these psychophysiological abnormalities but also psychological disturbances; i.e., overarousal and underarousal syndromes. Therefore, the dysfunction of the noradrenergic system might constitute an essential aspect of schizophrenic disorder. PMID- 7986772 TI - Effects of pharmacologic catecholamine manipulation on smooth pursuit eye movements in normals. AB - The pathophysiology of schizophrenia may be related directly or indirectly to abnormal dopaminergic activity. Both subcortical excess and frontal cortical deficiency of dopamine have been suggested, and primary or downstream failures of dopamine activation to the prefrontal cortex has been posited to explain some of the cognitive deficiencies in schizophrenia patients. Although the prefrontal cortex may also be a site for the disruption of smooth pursuit eye movements (SPEM), the most substantially described psychophysiological marker for schizophrenia vulnerability, no relationship of SPEM to dopaminergic activity has been demonstrated. In this study we explored the effect of altered dopamine function on SPEM quality through pharmacological manipulation of catecholamine tone in 11 healthy subjects. The subjects had SPEM measured at baseline, and under challenge conditions including amphetamine (0.3 mg/kg), haloperidol (2 mg), placebo, and combined amphetamine with haloperidol. Changes in the profile of mood scale (POMS) confirmed the expected subjective central nervous system effects the agents. Placebo and amphetamine had no effect on qualitative ratings of SPEM, but haloperidol, alone and in combination with amphetamine, disrupted eye tracking, producing a pattern of small saccadic intrusions characteristic of patients with schizophrenia. These findings link dopaminergic blockade with SPEM disruption in normal subjects. PMID- 7986773 TI - Cannabis and acute psychosis. AB - The Present State Examination was used to assess the psychopathology of 23 psychotic patients who were cannabis positive on urinary screening, and 46 matched drug-free controls. Cases and controls were indistinguishable in terms of psychopathology, DSMIII diagnoses, onset of recent illness, the proportion of first admissions, ethnicity, and socio-economic class, differing only in their histories of substance use. These data suggest that psychosis which develops or recurs in the context of cannabis use does not have a characteristic psychopathology or mode of onset, and is not restricted to a particular ethnic or socio-demographic group. There is thus little evidence to support the validity of 'cannabis psychosis' as a diagnostic entity. PMID- 7986774 TI - Effects of water loading in schizophrenic patients with polydipsia-hyponatremia: an MRI pilot study. AB - We conducted an MRI pilot study of three schizophrenic patients with the syndrome of polydipsia-hyponatremia. Paired MRI scans were obtained at baseline and in the water-loaded state to study the acute effects of water loading and accompanying changes in serum sodium and osmolality on brain structures. We report the pilot data on the observed individual MRI changes of reduced volume of the lateral ventricles in all three patients, and the third ventricles in two patients, in the water-loaded state. These changes were not statistically significant possibly because of small sample size. PMID- 7986776 TI - Further evidence for anomalies in the hand-prints of patients with schizophrenia: a study of secondary creases. AB - Finger and palm prints from 46 ICD-9 schizophrenic patients and 43 age and sex matched normal controls were examined independently and blind to diagnosis, by four raters. Seven prints were judged to have very high densities of secondary creases. These abnormal prints were all from the schizophrenic group. Patients with high densities of creases were more severely ill, having had more than five admissions to hospital and higher doses of neuroleptic medication. There was a trend for such patients to have had a complicated obstetric history and an earlier onset of their illness. PMID- 7986775 TI - Cerebrospinal fluid somatostatin concentrations in schizophrenia and schizoaffective disorder: the effects of antipsychotic treatment. AB - The authors examined the effects of antipsychotic treatment on cerebrospinal fluid somatostatin like immunoreactivity (CSF SLI) in 14 schizophrenic and 3 schizoaffective patients. There was a modest but significant increase in CSF SLI in 13 out of the 14 schizophrenic patients. In addition, there was a significant positive correlation between duration of treatment and post-treatment CSF SLI concentrations. No differential response was noted in patients also treated with the anticholinergic benztropine. PMID- 7986777 TI - Schizophrenia and the Cochrane Collaboration. Cochrane Collaboration Schizophrenia Review Group. PMID- 7986778 TI - Educational Family Therapy for schizophrenia: a new treatment model for clinical service and research. AB - A new family therapy model for schizophrenia is described, Educational Family Therapy (EFT). This model employs didactic teaching methods and 'user friendly' educational handouts and is provided in a flexible, interactive manner. The results of pilot data show that the model is feasible and suggest family members improve in their understanding of the illness. Data are also presented demonstrating that EFT can be distinguished from another model of family therapy for schizophrenia, Behavioral Family Therapy. The need for research comparing EFT and other family therapy models for schizophrenia is discussed. Such research may have implications for the dissemination of effective family interventions, matching treatment models to family needs and understanding the mechanisms underlying the impact of family therapy on the course of schizophrenia and on family burden. PMID- 7986779 TI - A review of the biostability and carcinogenicity of polyurethanes in medicine and the new generation of 'biostable' polyurethanes. AB - Polyurethanes are very versatile materials which have been used in the body for over 20 years. In fact, there are probably more scientific papers describing these materials and modifications of these materials for medical use than any other material to date. Unfortunately, some formulations of these polymers are subject to biodegradation and have limited their application in the body. Extensive investigation of the biodegradation mechanisms of these polymers by many researchers in the field has led to the development of a new generation of what are now called 'biostable' polyurethanes. This article reviews the history of polyurethane in medicine, polyurethane nomenclature, the biodegradation of these materials, the proposed mechanisms of its degradation as well as the carcinogenicity associated with these materials. Included in the discussion are the polyurethanes used as pacemaker lead insulators as well as those used to coat breast implants. The article concludes with a review of the new generation of 'biostable' polyurethanes and their proposed formulations. PMID- 7986780 TI - The adsorption of F(ab')2 on positively and negatively charged polystyrene beads. AB - An experimental study on the adsorption of F(ab')2 molecules onto positively and negatively charged polystyrene beads is described. Adsorption isotherms at low ionic strength and different pH were performed. In all cases the adsorption isotherms showed well-defined plateau. The positively charged polystyrene beads showed a higher adsorption of F(ab')2 molecules over a range of pH. This latex sample reached a maximum adsorption at pH 7, whereas the negatively charged sample showed a maximum at pH 5. The isoelectric points of the F(ab')2-PS complexes were around 7.5 and 4.5 respectively. The differences in the colloidal stability of the sensitized beads are not explained by the electrophoretic mobility values. The colloidal stability of the F(ab')2-PS complexes is not only determined by the electrical charge of the complexes but also by certain properties of the protein molecules, which can be closely related to the conformational changes undergone by the F(ab')2 molecules in the adsorption process on polymer surfaces. PMID- 7986781 TI - Antithrombogenicity of hydrophilic polyurethane-hydrophobic polystyrene IPNs. II. In vitro and ex vivo studies. AB - To investigate the effect of hydrophilic and hydrophobic surfaces with phase separated structure on their blood responses, interpenetrating polymer networks (IPNs) composed of hydrophilic polyurethane (PU) and hydrophobic polystyrene (PS) were prepared by simultaneous polymerization. In vitro protein adsorption, in vitro platelet adhesion, and ex vivo A-A shunt test were carried out to evaluate the blood compatibility of the PU/PS IPNs. The results of protein adsorption on the PU/PS IPN surfaces indicated that albumin preferentially adsorbed on the hydrophilic surface (PU), while fibrinogen preferentially adsorbed on the hydrophobic surface (PS). The PU/PS IPNs exhibited suppressive properties for both platelet adhesion and activation. The occlusion time of U50S50 IPN containing 50 wt% of PS was twice as long as that of the PU control (50 min), indicating enhanced blood compatibility, presumably due to the selective adsorption of plasma proteins and the suppression of the adhesion and activation of platelets. PMID- 7986782 TI - Deuterium dilution as a method for determining total body water: effect of test protocol and sampling time. AB - Deuterium dilution for the measurement of total body water (TBW) has been conducted using varying protocols for equilibration. We measured TBW from deuterium dilution in urine samples in twenty-eight subjects using three protocols: (1) early morning dosage without breakfast, measuring deuterium in a second voiding at 4 h and 6 h; (2) early morning dosage with breakfast with the same measurement times; (3) dosage as last consumption before overnight sleep, measuring deuterium in a second voiding at 10 h. Results were compared with TBW estimates from underwater weighing (UWW). Because UWW is an indirect measure of TBW, it is used as an independent reference method in order to compare only relative discrepancies between the two methods. TBW values in the fasted state were not significantly different from those obtained in the fed state. The urinary deuterium enrichment was higher at 4 h than at 6 h (resulting TBW differences: 0.6 (SD 0.4) l). At 4 h and 6 h, differences in TBW measurements from deuterium and densitometry were positively related to the amount of TBW, indicating incomplete equilibration in larger water compartments. At 10 h no such relationship existed, indicating complete mixing of deuterium. It is concluded that 10 h equilibration is preferable to the shorter 4 h and 6 h, for the determination of TBW. PMID- 7986783 TI - Effect of dietary protein quality, feed restriction and short-term fasting on protein synthesis and turnover in tissues of the growing chicken. AB - The effect of dietary protein quality and quantity on fractional rates of protein synthesis (ks) and degradation (kd) in the skeletal muscle, liver, jejunum and skin of young growing chickens was studied. Chickens were either fasted overnight or were fed at frequent intervals, using continuous feeders, with equal amounts of a diet containing soya-bean meal as the sole protein source, unsupplemented, or supplemented with either lysine or methionine. Each of the three diets was provided at 2 or 0.9 x maintenance. On the higher intake, birds on the unsupplemented diet gained weight, lysine supplementation decreased and methionine supplementation increased body-weight gain (by -23% and +22% respectively). Birds fed at 0.9 x maintenance lost weight; supplementation with methionine or lysine did not influence this weight loss. None of the dietary regimens had significant effects on protein synthesis rates in any of the tissues, thus the mechanism whereby muscle mass increased in response to methionine supplementation appeared to be a decrease in the calculated rate of protein degradation. Similarly, on the 0.9 x maintenance diet the failure of the animals to grow appeared to be due to an increase in the rate of protein degradation rather than an effect on synthesis. Conversely, muscle ks was decreased in fasted chickens previously fed on the unsupplemented diet at 2 x maintenance, and in birds which had received the 0.9 x maintenance diet fasting resulted in a similar reduction in protein synthesis in muscle; ks in the liver and jejunum was also significantly decreased.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7986784 TI - Gastro-jejunal digestion of soya-bean-milk protein in humans. AB - In order to determine how soya-bean proteins are digested and metabolized in the human intestine before colonic bacterial fermentation and to estimate their true digestibility, the gastro-jejunal behaviour of soya-bean proteins in water and in two other forms (a concentrated soya-bean-protein solution (isolate) and a drink composed of crude soya-bean proteins (soymilk)) was studied in humans. Experiments were carried out in eight healthy volunteers using a double-lumen steady-state intestinal perfusion method with polyethyleneglycol (PEG) as a non absorbable volume marker. Gastric emptying and N and electrolyte contents of the jejunal digesta were analysed. Gastric half-emptying time (min) of the liquid phase after water ingestion (12.59 (SE 0.12)) was shorter (P < 0.05) than those for soymilk (37.74 (SE 11.57)) and isolate (36.52 (SE 11.23)). Electrolytic balances showed that for all meals, Na+, Cl- and K+ were secreted when Ca2+ was efficiently absorbed from the jejunal lumen. Gastro-jejunal N absorption for isolate and soymilk were 63 and 49% respectively, and were not significantly different from one another; after water ingestion, endogenous N was estimated to be 21 mmol. An estimate of the exogenous:endogenous values for the effluents was obtained from the amino acid compositions of soymilk and effluents after water or soymilk ingestion, indicating that 70% of the total N was exogenous and 30% endogenous. Under these conditions the endogenous fraction represented 31 mmol after soymilk ingestion and the gastro-jejunal N balance indicated that 54% of the soymilk was absorbed. This finding indicates that the true gastrojejunal digestibility of soya-bean proteins is similar to that of milk proteins. PMID- 7986785 TI - Pancreatic digestive hydrolase activities in growing rats fed alternately on raw and heated soya-bean flour. AB - The time-course effects of two diets containing raw (RSF) or heated (HSF) soya bean flour on the digestive enzyme levels in the pancreas and in pancreatic juice were investigated in growing rats fed, alternately, on RSF or HSF diets for two 4 week periods. These values were compared with those obtained in a control group fed on a casein diet. RSF and HSF diets lowered N balance (84.8 (SE 0.9), 82.6 (SE 0.8) and 79.9 (SE 0.8)% with control, HSF and RSF diets respectively, at the third week). However, they increased protease activities compared with the control diet (3-fold for trypsin (EC 3.4.21.4) and chymotrypsin (EC 3.4.21.1) activities in pancreas contents and outputs with the RSF diet; 2-fold for trypsin in pancreas contents and outputs and by 60% for chymotrypsin contents with the HSF diet). The poorer nutritional N utilization might be attributable to soya bean flour heat-stable (lectins) and heat-labile components (trypsin inhibitors). The decrease in lipid apparent digestibilities in RSF and HSF diets (97.0 (SE 0.8), 91.1 (SE 0.9) and 90.4 (SE 0.7)% with control, RSF and HSF diets at the seventh week) were correlated with a diminution in apparent lipase (EC 3.1.1.3; measured without addition of exogenous colipase), potential lipase (measured with addition of saturated amounts of exogenous colipase) and colipase activities. Compared with control values, gains in potential and apparent lipase outputs were diminished by nearly 40% and gain in colipase outputs by 60% with RSF and HSF diets. These results show clearly that heated or raw soya-bean flours have a significant inhibitory effect on lipase digestive enzyme activities in the pancreas and in its secretion, which might explain impaired lipid digestibility. PMID- 7986787 TI - Changes in plasma phospholipid fatty acids and their relationship to disease activity in rheumatoid arthritis patients treated with a vegetarian diet. AB - In a controlled clinical trial we have recently shown that patients with rheumatoid arthritis (RA) improved after fasting for 7-10 d and that the improvement could be sustained through 3.5 months with a vegan diet and 9 months with a lactovegetarian diet. Other studies have indicated that the inflammatory process in RA can be reduced through manipulation of dietary fatty acids. A switch to a vegetarian diet significantly alters the intake of fatty acids. Therefore, we have analysed the changes in fatty acid profiles of the plasma phospholipid fraction and related these changes to disease activity. The concentrations of the fatty acids 20:3n-6 and 20:4n-6 were significantly reduced after 3.5 months with a vegan diet (P < 0.0001 and P < 0.01 respectively), but the concentration increased to baseline values with a lactovegetarian diet. The concentration of 20:5n-3 was significantly reduced after the vegan diet (P < 0.0001) and the lactovegetarian diet periods (P < 0.01). There was no significant difference in fatty acid concentrations between diet responders and diet non responders after the vegan or lactovegetarian diet periods. Our results indicate that the changes in the fatty acid profiles cannot explain the clinical improvement. PMID- 7986786 TI - Intestinal absorption of medium chain fatty acids: in vivo studies in pigs devoid of exocrine pancreatic secretion. AB - In order to study the influence of pancreatic enzyme secretion on the intestinal absorption of medium-chain fatty acids (MCFA), three growing pigs (mean body weight 61 kg) with ligated and severed pancreatic ducts were fitted with a permanent fistula in the duodenum and with two catheters in the portal vein and carotid artery respectively. An electromagnetic flow probe was also set up around the portal vein. A mixture of octanoic and decanoic acids, esterified as medium chain triacylglycerols, together with maltose dextrine and nitrogenous fraction was continuously infused for 1 h into the duodenum. Samples of blood were withdrawn from the two vessels at regular intervals of time for 8 h and further analysed for their non-esterified octanoic and decanoic acid contents. The concentrations of non-esterified octanoic and decanoic acid in the portal blood increased slowly after the beginning of each infusion, reaching about 10 times higher values than the basal level. Only 26% of octanoic acid infused in the duodenum and 27% of decanoic acid were recovered in the portal flow throughout each experiment. The possible mechanisms underlying the appearance of MCFA in the portal blood in the absence of pancreatic enzyme secretions and the importance of duodenal absorption of MCT in such physiological conditions have been discussed. PMID- 7986788 TI - Dietary fructose v. glucose in rats raises urinary excretion, true absorption and ileal solubility of magnesium but decreases magnesium retention. AB - Apparent Mg absorption, that is Mg intake minus faecal excretion, was found to be greater in rats fed on diets containing fructose instead of glucose. This effect of fructose was accompanied by enhanced urinary excretion and diminished retention of Mg. True Mg absorption was then determined with the use of oral and intraperitoneal administration of tracer doses of 28 Mg. True Mg absorption was significantly greater in rats fed on fructose. There was no significant effect of fructose v. glucose on faecal excretion of endogenous Mg. It was hypothesized that fructose enhances the solubility of Mg in the ileal lumen and thereby facilitates its absorption. The distribution of Mg between the solid and liquid phases of the ileum was determined in rats fed on either glucose or fructose. Fructose reduced the amount of Mg in the solid phase but raised both the amount and the concentration of Mg in the liquid phase. We conclude that the dietary fructose-induced stimulation of Mg absorption in rats is caused by a raised solubility of ileal Mg, but the mechanism by which fructose exerts this effect and why it was not associated with a decrease in faecal excretion of endogenous Mg remain unknown. Dietary fructose v. glucose did not systematically affect the apparent absorption of Ca and P. PMID- 7986789 TI - Fibre-mediated physiological effects of raw and processed carrots in humans. AB - Fibre-mediated physiological effects of raw and processed carrots were investigated in twenty-four young women under strict dietary control in two randomized crossover studies. For 3 weeks between 405 and 688 g of either raw frozen, blanched or canned carrots (first study), or raw or raw frozen carrots (second study) were consumed in addition to a low-fibre basal diet. Carrots provided 15 g dietary fibre (DF)/d. Total DF intake was 16.0 to 19.0 g (control periods) and 31 to 34 g (experimental periods). Faecal bulking effects of raw and processed carrots were similar (between 2.4 and 3.7 g additional stool/g carrot fibre in the diet). Faecal excretion of dry matter, fibre, and protein also increased significantly during carrot consumption. Fermentability of carrot fibre constituents was high (91-94%) and independent of processing, in spite of differences in the distribution of soluble and insoluble fibre and in the texture of raw and processed carrots. There was no effect of either type of carrot on serum total and high-density-lipoprotein-cholesterol or on faecal bile acid excretion. PMID- 7986790 TI - Biochemical indices and neuromuscular function tests in rural Gambian schoolchildren given a riboflavin, or multivitamin plus iron, supplement. AB - Ninety preselected children, aged between 8 and 14 years, living in two rural West African (Gambian) villages, were randomly divided into three groups, matched for age and sex. One group received a placebo (lactose) tablet, one received riboflavin (5 mg) on 5 d every week, which was sufficient to correct an endemic riboflavin deficiency, and one received a multivitamin supplement (Protovit; Hoffmann La Roche), on 5 d every week, together with FeSO4 (200 mg) once weekly, and the supplements were given for 1 year. Neuromuscular tests, including arm tremor and manipulative skills, were performed on three occasions: once just before the introduction of the supplements; again 6 weeks after commencing the supplements; and again 1 year later. Venous blood samples were collected at the same time as the first two sets of neuromuscular tests. These samples were used for haematology and nutrient status indices: plasma ferritin, ascorbic acid, cyanocobalamin and pyridoxal phosphate, and erythrocyte tests for folate status, for riboflavin status (erythrocyte glutathione reductase activation coefficient) and thiamine status (erythrocyte transketolase activation coefficient). The riboflavin in both supplements achieved a clear-cut response in biochemical status, which was dose-dependent. The pyridoxine, ascorbic acid and Fe components of the multivitamin also affected the associated biochemical indices. Although overall the arm tremor and related neuromuscular function tests did not respond significantly to the supplements, significant improvement was seen in the boys for the arm-tremor test in both the supplemented groups. PMID- 7986791 TI - Effects of mild zinc deficiency, plus or minus an acute-phase response, on galactosamine-induced hepatitis in rats. AB - Zn deficiency is hypothesized to produce poor resistance to injury involving oxidative stress. This could occur by impairing Zn antioxidant function(s) or by indirectly limiting adaptive protective mechanisms such as a rise in acute-phase proteins. The present study examined rats fed diets adequate or moderately low in Zn (4 or 25 micrograms/g diet) for 9 d. The lower intake produced a mild Zn deficiency based on body weight, plasma Zn and plasma alkaline phosphatase (EC 3.1.3.1) activity. Galactosamine injection, an oxidative stress, produced much more liver injury in the mildly Zn-deficient rats. However, injury was strongly inhibited in rats from each dietary group by an acute-phase response due to turpentine-induced leg inflammation. Mild Zn deficiency did not prevent a rise in levels of the acute-phase protein caeruloplasmin (EC 1.16.3.1), but did limit the usual inflammation-induced rise in hepatic levels of metallothionein, a Zn protein with possible antioxidant function. In conclusion, high degrees of galactosamine-induced hepatitis were associated with mild Zn deficiency, but the liver injury was blocked by prior stimulation of an acute-phase response, regardless of Zn status. PMID- 7986792 TI - Comparison of dietary assessment methods in nutritional epidemiology: weighed records v. 24 h recalls, food-frequency questionnaires and estimated-diet records. AB - Women (n 160) aged 50 to 65 years were asked to weigh their food for 4 d on four occasions over the period of 1 year, using the PETRA (Portable Electronic Tape Recorded Automatic) scales. Throughout the year, they were asked to complete seven other dietary assessment methods: a simple 24 h recall, a structured 24 h recall with portion size assessments using photographs, two food-frequency questionnaires, a 7 d estimated record or open-ended food diary, a structured food-frequency (menu) record, and a structured food-frequency (menu) record with portion sizes assessed using photographs. Comparisons between the average of the 16 d weighed records and the first presentation of each method indicated that food-frequency questionnaires were not appreciably better at placing individuals in the distribution of habitual diet than 24 h recalls, due partly to inaccuracies in the estimation of frequency of food consumption. With a 7 d estimated record or open-ended food diary, however, individual values of nutrients were most closely associated with those obtained from 16 d weighed records, and there were no significant differences in average food or nutrient intakes. PMID- 7986793 TI - Alterations in vascular pattern of the developing palate in normal and spontaneous cleft palate mouse embryos. AB - The alterations in the vascularization of the developing palate were studied through the use of resin cast images of vascular networks in normal and spontaneous cleft lip and palate (CL/Fr) mouse embryos (crown rump [CR] Length 9 18 mm, body wt. 0.11-0.65 g). A more dense vascular plexus was observed in the oral side than in the nasal side before the reorientation of the palatal shelves. Prominent terminal dilatations of the vascular plexus were observed in the extreme medial edge of the elevating palatal shelves which may exert significant force for palatal shelf elevation. The vascular plexus showed a lateral extension. Many small spherical masses of resin were observed in the medial edge of the palatal shelves at the time of medial extension and during fusion, indicating some changes occurring in the capillary wall leading to the resin leakage. In the spontaneous cleft group, a similar vascular pattern was observed, but the greater palatine artery showed discontinuity in the premaxillary region at an early stage. At the same time, terminal dilatations were delayed and frequently absent in the contralateral shelf. After the reorientation of the palatal shelves, the vascular plexus formed an irregular lattice pattern. Dilated vasculature was apparent in the anterior nasopalatine region, indicating the persistence of a more primitive vascular structure in the spontaneous cleft embryos. However, the area where capillary dilatation occurred was different between unilateral and bilateral cleft embryos. In conclusion, blood vessels in the palatal shelves are underdeveloped and remained immature in cleft lip and palate embryos and showed different patterns in the anterior nasopalatine region between unilateral and bilateral cleft embryos. These variant vascular patterns may be due to the inadequate blood supply to the nasopalatine region from the early embryonic stages possibly resulting from the discontinuity of the greater palatine artery. PMID- 7986794 TI - Patterns of abnormal myogenesis in human cleft palates. AB - To test the hypothesis that soft palate muscles are abnormal in cleft palate, we compared soft palate morphogenesis in fetuses with cleft palate (n = 4) to age matched (n = 3) and nonmatched (n = 1) control specimens. The morphologic status of all soft palate and masticatory structures were classified into one of six stages based on the level of histogenesis. At 54 mm crown-rump length (CRL), the levator veli palatini (L), palatopharyngeus (PP), and palatoglossus (PG) in cleft subjects demonstrated mesenchymal condensation into myoblastic fields, lagging behind the control specimens (97 mm CRL), which displayed definitive fields of myoblasts and myotube formation. In the 175 mm and 225 mm cleft and the 170 mm and 192 mm control specimens, muscular morphology was similar and had reached its postnatal appearance for the tensor veli palatini (175 m only) and L, PP, PG (225 mm only). Muscle fiber directions were, however, disoriented and disorganized, especially close to the medial epithelial edge of the cleft. The levator veli palatini, could not be distinguished as a discrete muscle in the cleft specimens, and what we believed to be the PP and PG seemed "normal" at the level of light microscopy, but malpositioned in a superior direction. This preliminary study demonstrates for the first time that early myogenesis in cleft palates differs from normal. PMID- 7986795 TI - Induction of cleft palate by gamma-irradiation of prenatal CD-1 mice. AB - Fetuses of pregnant mice exposed to whole body gamma-irradiation (400 rads) on the 12th gestational day were compared with control fetuses to assess the effect of radiation on palatogenesis. Experimental and control groups were sacrificed on day 18 of gestation. The fetuses were removed via laparotomy and counted to determine the litter size. Animals were decapitated and the maximum head height, width, and circumference recorded. For light microscopic examination of palatogenesis, heads were fixed in Bouin's solution and prepared for paraffin sectioning and staining with hematoxylin and eosin. A significant reduction in litter size (p < .0025) and head measurements (p < .005) of irradiated fetuses was observed when compared to those of the control group. Histologic examination of serial coronal sections demonstrated that 100% of the experimental fetuses had palatal clefts. It was concluded that gamma-rays have adverse effects on the litter size, head measurements, and palatal closure of mouse fetuses. PMID- 7986796 TI - Measurement of velopharyngeal closure force during vowel production. AB - The purposes of this study were to (a) design and test a new velopharyngeal closure force sensing bulb, and (b) use the closure force bulb to gather additional information on the variations in closure force associated with different vowels. The closure force sensing bulb possessed a flat frequency response to 30 Hz. Its output was highly linear relative to applied gram force. Reliable placement of the bulb in human subjects was achieved following prescribed placement criteria. The bulb was sensitive to small variations in velopharyngeal closure force. In agreement with some previous reports, high vowels were associated with greater velopharyngeal closure forces than low vowels. The results of this investigation support the notion that articulatory goals are specified for vowels. This vowel specificity was observed during production in both isolation and in context. PMID- 7986797 TI - Cleft palate with autosomal recessive transmission in Brittany spaniels. AB - In the course of maintaining a large colony of Brittany spaniels for studying a dominantly inherited motor neuron trait, cases of sporadic complete cleft palate were observed. Without intervention, the pups with cleft palate that attempt to nurse, aspirate and die. In this study, we report on the incidence of cleft palate in this dog kindred, describe the gross morphologic characteristics of the cleft, and present a morphometric analysis of the skull of two of the cleft palate pups and one unaffected pup that died at birth. Our data thus far indicate 26.9% incidence of cleft palate in the colony. Pedigree analysis indicates that this cleft palate trait is inherited as an autosomal recessive. High resolution computed tomography scans of the pup heads were used in morphometric comparison of normal and cleft palate pups. We found specific morphologic differences between the cranial base and palate of normal and cleft palate pups. Plans for future studies of the genetics and growth and development of this animal model are discussed. This canine cleft palate trait provides an ideal model for studying a malformation common in humans. PMID- 7986798 TI - Dentofacial form in the five-year-old child with unilateral cleft lip and palate. AB - It is generally believed that studies of outcome for children with clefts of the lip and palate should be based on patients who are in their teens. This means that health care workers who look after these children would have to wait many years until the quality of treatment could be evaluated. In this study, significant differences between two centers, Oslo and Manchester, in facial form at the age of 5 years were detected. Based on cephalometric analysis, children from Manchester were more likely to have a retrognathic maxilla with the upper lip significantly behind the esthetic plane. An important future step may be the setting up of "reference centers" with a large archive of database information for each racial group. This would assist smaller centers in comparing their outcomes. PMID- 7986799 TI - Palatal changes after lip surgery in different types of cleft lip and palate. AB - This study concerns palatal development during 6 months following primary lip closure. The sample consisted of 75 children with different forms of cleft lip and palate and 51 noncleft children. The palate was measured at 3 months of age, just before lip surgery, after surgery at 6 months, and again at 9 months of age. The results showed that lip closure has a strong effect in the anterior alveolar region. This effect was restricted to 3 months after surgery. The changes in complete clefts were more explicit than in incomplete cleft forms. Furthermore, the data showed that arch depth reduction due to lip surgery was compensated for by continued anteroposterior palatal growth. Early orthopedics appeared to prevent major palatal collapse immediately after lip surgery. Finally simultaneous closure of the alveolar cleft at the nasal side resulted in continued reduction of anterior cleft width. PMID- 7986801 TI - Midline defects of the orofaciodigital syndrome type VI (Varadi syndrome). AB - The orofaciodigital syndromes (OFDS) represent a spectrum of anomalies of the palate, cranium, hands, and feet. Varadi syndrome, designated OFDS type VI, is a rare disorder that is additionally characterized by cerebellar anomalies. The following report is of a patient with OFDS VI and characteristic multiple midline defects: median cleft lip and palate, lingual cleft with nodules, and midline brain malformation. In addition, this case is uniquely associated with the presence of midline (metopic and sagittal) craniosynostoses as well. It is unusual that deformities which result from premature fusion of cranial vault sutures would appear synchronously in a syndrome based on the concept of failure of fusion or coalescence of facial growth centers. The midline represents an independent developmental field, whereby CNS defects and midline anomalies can present concurrently. PMID- 7986800 TI - Effect of premature sagittal suture closure on craniofacial morphology in a prehistoric male Hopi. AB - Scaphocephaly is caused by premature sagittal suture closure. It restricts medial lateral growth of the cranial vault which appears longer and narrower than normal. We examined how this natural malformation affected morphology of the cranial base and face. A prehistoric adult male Hopi with scaphocephaly was compared to 19 normal male Hopi (Old Walpi Series, Field Museum of Natural History, Chicago, IL). Three-dimensional coordinates of 53 landmarks were recorded on the cranial vault, cranial base, and face. Finite element scaling analysis was used to test for significant differences between the scaphocephalic and normal individuals in craniofacial morphology. Finite element scaling results indicated that scaphocephaly has a profound effect on cranial vault morphology. However, morphology of the cranial base and face were only slightly affected and, typically, are within the normal range of variation for the sample. An abnormality in the cranial base is not associated with scaphocephaly in this individual. PMID- 7986802 TI - Orodigitofacial syndromes type I and II: clinical and surgical studies. AB - Eleven patients were followed at the multidisciplinary facial cleft department from 1963 to 1993. Nine had orodigitofacial (ODF) I syndrome (Papillon-Leage, 1954) and two had ODF II syndrome (Mohr, 1941). The authors observed seven median clefts of the upper lip, eight atypical cleft palates, nine lingual tumors, ten polylobed tongues, four ankyloglossia. All vestibular frenula were hypertrophied. Facial analysis showed five facial hypertelorisms, eight epicanthal folds, ten anomalies of the forehead. Nasal anomalies were constant with ten alar hypoplasia and four nasal curves. Syndactyly was the most frequent anomaly of the hand. Seven patients were mentally retarded. Transmission of ODF I is by X-linked dominant variable expression; ODF II is autosomal recessive. The difference in transmission means a precise diagnosis is necessary. Bilateral duplication of the great toe is characteristic of type II, but not pathognomonic. Hair and cutaneous anomalies suggest type I. The authors proposed a surgical treatment involving three operating steps. PMID- 7986803 TI - Effect of presurgical infant orthopedics on facial esthetics in complete bilateral cleft lip and palate. PMID- 7986804 TI - The relationship between phospholipid content and Ca2+-ATPase activity in the sarcoplasmic reticulum. AB - The relationship between the phospholipid composition of sarcoplasmic reticulum and the activity of the Ca2+, Mg2+-stimulated ATPase was analyzed by digestion of membrane phospholipids with phospholipase C and A2 enzymes of diverse specificity and by detergent extraction. Phospholipase C of Clostridium perfringens and Clostridium welchii, that hydrolyze preferentially phosphatidylcholine (PC), inhibited the Ca2+-ATPase activity parallel with the depletion of phosphatidylcholine from the membrane. Phospholipase C of Bacillus cereus hydrolyzed in addition to PC, phosphatidylethanolamine (PE) and phosphatidylserine (PS), causing complete inhibition of Ca2+-stimulated ATPase activity. Digestion of sarcoplasmic reticulum with the phospholipase A2 of snake or bee venom produced similar effects. The phosphatidylinositol (PI)-specific phospholipases of B. cereus and Bacillus thuringiensis caused less than 10% inhibition of the Ca2+-ATPase, accompanied by the hydrolysis of more than 70% of the phosphatidylinositol content of the membrane, without significant change in PC, PE and PS content. The inhibition of ATPase activity by the C type phospholipases was nearly completely reversed by octaethyleneglycol dodecyl ether (C12E8). These experiments suggest that the full phospholipid content of native sarcoplasmic reticulum (congruent to 100 mol phospholipid per mol Ca2+-ATPase), is required for ATPase activity and there is no indication that PE, PS, and PI play a specific role in ATP hydrolysis. Extraction of sarcoplasmic reticulum phospholipids by detergents such as deoxycholate, cholate and C12E8 also caused proportional inhibition of ATPase activity with the decrease in phospholipid content; the parallel extraction of PC, PE and PI left the phospholipid composition largely unchanged during delipidation. These observations do not support the requirement for a 'lipid annulus' of congruent to 30 phospholipid molecules/Ca2+-ATPase as proposed by Hesketh et al. ((1976) Biochemistry 15, 4145 4151) or the specific interaction of phosphatidylethanolamine with the ATPase molecule proposed by Bick et al. ((1991) Arch. Biochem. Biophys. 286, 346-352). PMID- 7986805 TI - Mechanism of alanine excretion in recombinant strains of Zymomonas mobilis. AB - A thiamine-auxotrophic strain of Zymomonas mobilis (CP4thi/pZY73), in which the alaD gene of Bacillus sphaericus coding for the alanine dehydrogenase was expressed, synthesizes and excretes alanine at high rates after thiamine starvation and in the presence of high external ammonium concentrations. The mechanism of alanine excretion was studied in this recombinant Zymomonas mobilis strain. Under production conditions the internal alanine concentration reached values of up to 280 mM and excretion rates of up to 140 nmol min-1 mg dry mass-1 were obtained. The membrane integrity and the energetic properties of the cells remained intact and were comparable to growing wild-type cells. Unspecific leakage of solutes was not observed. We did not find any indication of a carrier mediated excretion of alanine, since typical properties of this type of mechanism, i.e., saturation at increasing internal substrate concentration, substrate specificity and functional inhibition were absent. Furthermore, a counterflow maximum, which would indicate the involvement of a carrier protein, was not observed either. Consequently, alanine excretion in recombinant Z. mobilis cells is interpreted as mediated by simple diffusion through the intact cytoplasmic membrane at high rates (diffusion constant 10(-8) l s-1 mg dry mass-1 or 0.28 min-1). For comparison, the diffusion constant for alanine efflux was also measured in Corynebacterium glutamicum cells and the values obtained were significantly lower than those determined in Z. mobilis. The consequences of this finding are discussed. PMID- 7986806 TI - Putative cytoplasmic amphiphilic domains in the nerve growth factor/tumour necrosis factor receptor superfamily. AB - Potential alpha-helical regions in cytoplasmic domains of the NGF/TNF receptor superfamily were searched to identify amphiphilic sequences favouring association with membrane surfaces, analogous to the predicted secondary structure of mastoparan (MP). Similar to MP, NGFR (rat, chick, human), human TNFR-1, and human 4-1BB have domains with putative surface membrane associating sequences. The circular dichroism spectra of mastoparan and a peptide homologous to the putative amphiphilic domain of NGFR were identical in an aqueous milieu, and both adopted an alpha-helical conformation in trifluoroethanol. PMID- 7986807 TI - Separation and characterization of Na+,K(+)-ATPase containing vesicles. AB - Na+,K(+)-ATPase was reconstituted in vesicles prepared by a dialysis method. Ion exchange chromatography was used to obtain well characterized fractions from the inhomogeneous vesicle preparation. Lipid and protein content was determined by optical methods during the elution process. It was possible to separate fractions with distinct enzymatic and transport activities. A protocol was set up, which allowed to calculate the average number of 5-IAF labeled ion pumps per vesicle in the different fractions. The dependence of the number of protein molecules per vesicle was studied as function of the initial protein concentration added to the lipid solution before dialysis. The transport activity disappears completely at very low protein concentrations (3.3 micrograms protein per mg lipid). This observation is in favor of the proposal discussed in the literature, that the heterodimer (alpha beta)2 is the transport-active form of the Na+,K(+)-ATPase. The presented method can be applied to all reconstituted vesicle preparations in which the proteins can be labeled quantitatively with a fluorescence dye. PMID- 7986808 TI - Acylation of proteins of the archaebacteria Halobacterium cutirubrum and Methanobacterium thermoautotrophicum. AB - Although the membrane lipids of extremely halophilic archaebacteria are exclusively derived from diphytanylglycerol diether, which is non-acylated, small amounts of fatty acids have been detected in these organisms. These fatty acids are formed by the action of a fatty acid synthase (FAS), shown to be present in the extreme halophile Halobacterium cutirubrum, despite the fact that only a fraction of the activity of FAS remains at the high salt concentration (> 4 M) present in the cytoplasm. It has now been demonstrated that fatty acids do not occur in lipid-bound form but largely in the form of acylated proteins in the red membrane of H. cutirubrum. In contrast, the bacteriorhodopsin of the purple membrane of this extreme halophile does not appear to be acylated. The thermophilic methanogen, Methanobacterium thermoautotrophicum had a much higher fatty acid synthase activity than the extreme halophile, and the synthase activity of the methanogen was optimal under its normal (anaerobic) growth conditions. The methanogen also utilized the resulting fatty acids to acylate its membrane proteins. The major fatty acids in both organisms were palmitic and stearic acids with small amounts of myristic and 18:1 acids, and these were bound to protein through both ester and amide linkages. PMID- 7986809 TI - Coordinate induction of Na(+)-dependent transport systems and Na+,K(+)-ATPase in the liver of obese Zucker rats. AB - Solute uptake into liver plasma membrane vesicles from either lean or obese Zucker rats was monitored. D-Glucose and L-leucine uptakes at physiological concentrations of the substrate were not different in lean and obese Zucker rats. In agreement with a previous report (Ruiz et al. (1991) Biochem. J. 280, 367-372) L-alanine uptake was significantly enhanced in those preparations from obese animals. Na(+)-coupled uridine transport was markedly enhanced also in obese rats. The effect was due to an increase in Vmax (5.5 +/- 0.6 vs. 2.1 +/- 0.2 pmol/mg protein per 3 s, P < 0.01) without any significant change in Km (11.0 +/- 2.8 vs. 9.0 +/- 2.7 microM for obese and lean rats, respectively). Na+,K(+) ATPase activity was also higher in liver plasma membrane vesicles from rat liver and it correlated with a higher amount of alpha 1-subunit protein in both, plasma membrane vesicles and homogenates from obese rat livers. In summary, in the hypertrophic liver of obese Zucker rats a coordinate induction of several Na(+) dependent transport systems occurs and, in order to sustain the metabolic pressure associated with this adaptation, a significant induction of the Na+,K(+) ATPase expression is also found. These data also provide new evidence for regulation of the recently characterized Na(+)-dependent nucleoside transporter. PMID- 7986810 TI - Spin label EPR study of lipid solvation of supramolecular photosynthetic protein complexes in thylakoids. AB - Lipid-protein association in the chloroplast membrane and its various thylakoid fractions from higher plants, namely pea and maize, rich in Photosystem I (PSI) and Photosystem II (PSII), respectively, were studied using EPR spectroscopy of spin-labelled lipid molecules. All the EPR spectra consisted of two spectral components corresponding to bulk fluid lipids and solvation lipids motionally restricted at the hydrophobic surface of membrane proteins. Spin-labelled stearic acid and phosphatidylglycerol exhibited marked selectivity towards the supramolecular protein complexes of both PSI and PSII although to different extent. In addition, lipid-protein titration experiments are described for partially delipidated PSII-enriched membrane fractions of pea chloroplasts, incorporating unlabelled egg phosphatidylcholine prior to or after the incorporation of spin-labelled lipids. Two sets of solvation sites were resolved by timed labelling experiments and a significant result of these studies was that a well-defined population of solvation sites (approx. 100 mol lipids/820 kDa protein) was rapidly exchanged by laterally diffusing membrane lipids, while other solvation sites (approx. 50 mol lipids/820 kDa protein) were exchanged much slower or not exchanged at all. PMID- 7986812 TI - Entrapment of haemoglobin into liposomes by the dehydration-rehydration method: vesicle characterization and in vivo behaviour. AB - Haemoglobin (Hb) was isolated from human erythrocytes under conditions which maintained NADH-cytochrome-b5 reductase activity and suppressed oxidation of Hb during storage at 4 degrees C (methaemoglobin values < 3% after 29 days). Hb was entrapped into liposomes composed of hydrogenated egg phosphatidylcholine and equimolar cholesterol according to the dehydration/rehydration procedure of Kirby and Gregoriadis ((1984) Biotechnology 2, 979). However, encapsulation of Hb in its intact form was poor (< 5%) as a result of its oxidation and denaturation during freeze-drying. The addition of cryoprotectants and the use of both, higher initial concentrations of Hb and very small void vesicles resulted in Hb-rich dehydration/rehydration vesicles (phospholipid/Hb molar ratio of about 200:1) of the preferred size of 110 nm (mean). Highly homogeneous and small void vesicles as starting material were prepared using the one-step method of Brandl et al. ((1990) Drug Dev. Ind. Pharm. 16, 2167). The cryoprotectants were chosen with respect to their sufficient protection of Hb without affecting its loading into vesicles during freeze-drying and rehydration. 51Cr-labelling of Hb was used for the in vivo monitoring of the fate of Hb-containing vesicles rather than 125I labelling since the latter induced strong interactions of Hb with liposomes. Upon intravenous administration into rats, liposomal 51Cr-Hb showed greater blood levels and prolonged circulation times in the blood compared to free Hb. The present approach provides high yield entrapment of labile molecules into vesicles of small size known to exhibit long circulation time. PMID- 7986811 TI - The targeting of phospholipid liposomes to bacteria. AB - Phospholipid liposomes have been prepared from phospholipid mixtures including dipalmitoylphosphatidylcholine/phosphatidylinositol (DPPC/PI) and DPPC/dipalmitoylphosphatidylglycerol (DPPC/DPPG) mixtures and targeted to adsorbed biofilms of the skin-associated bacteria Staphylococcus epidermidis and Proteus vulgaris and the oral bacterium Streptococcus sanguis. The effects of time, liposome concentration and density of bacteria in the biofilm have been studied in detail for Staphylococcus epidermidis. The targeting (as assessed by the apparent monolayer coverage of the biofilms by liposomes) to the biofilms was found to be sensitive to the mol% of PI and DPPG in the liposomes and optimum levels of PI were found for targeting to each bacterium. The use of PI and DPPG containing liposomes for the delivery of the bactericide, Triclosan, to biofilms of Staphylococcus epidermidis was studied as a function of the amount of Triclosan carried by the liposomes. All the liposome systems tested inhibited the growth of bacteria from the biofilms after brief (2 min) exposure to Triclosan carrying liposomes. At low Triclosan levels bacterial growth inhibition by Triclosan-carrying liposomes exceeded that by an equivalent level of free Triclosan. After short periods (min) of exposure of biofilms to Triclosan carrying liposomes the bactericide was shown to preferentially concentrate in the biofilms relative to its liposomal lipid carrier. The results suggest that phospholipid liposomes with appropriately chosen lipid composition have potential for the targeting and delivery of bactericide to bacteria. PMID- 7986813 TI - Early and delayed stages in the solubilization of purple membrane by a polyoxyethylenic surfactant. AB - The purpose of this paper is to explore the reasons by which purple membrane solubilization by detergents takes hours, or even days, to reach equilibrium, while most biomembranes are solubilized in a matter of seconds, or minutes. With that aim, changes in the purple membrane absorption spectrum produced by hydrogenated Triton X-100 under equilibrium conditions (24 h) have been compared to those caused by the same surfactant in the minute, second and sub-second time scale. It is found that the various processes that accompany, or lead to, solubilization are already detected, and even reach an apparent equilibrium, in the 10 s that follow detergent addition. No new phenomena are detected in the following minutes, or hours, that are relevant to the process under study. This leads to the conclusion that the long solubilization process consists of the repeated operation of simple phenomena that are relatively fast in themselves. A hypothesis is proposed according to which the tight crystalline organization of the purple membrane prevents the insertion of detergent monomers in the lipid bilayer; instead, the surfactant would bind the periphery of the patches, i.e., the hydrocarbon-water contact region, and solubilization would take place gradually, from the periphery towards the core of the membrane patches, at a progressively lower rate as the amounts of free detergent and detergent-binding sites are decreased by the previous solubilization steps. PMID- 7986814 TI - Presence of membrane-bound proteinases that preferentially degrade oxidatively damaged erythrocyte membrane proteins as secondary antioxidant defense. AB - Human erythrocytes were oxidized with xanthine/xanthine oxidase/ferric ion or ADP/ferric ion at 37 degrees C for several hours. Band 3 protein and spectrin of the oxidized cells were found to be significantly modified as analyzed by radiolabeling with tritiated borohydride. Sodium dodecylsulfate-polyacrylamide gel electrophoresis of the xanthine/xanthine oxidase/ferric iron-oxidized cells and subsequent immunoblotting with anti band 3 protein showed that band 3 protein was fragmented into smaller molecular-weight fragments. When the cell membrane obtained from the oxidized cells were incubated at pH 7.4 and 37 degrees C for several hours in the presence of alpha-tocopherol, extensive degradation of band 3 protein and spectrin was observed. Band 3 protein was found to be most susceptible to the degradation. Degradation of band 3 protein was also observed after similar incubation of the membrane from the ADP/ferric ion-oxidized cells. Membrane-bound serine- and metalloproteinases were responsible for the degradation of band 3 protein, because the degradation was remarkably inhibited by diisopropyl fluorophosphate and phenylmethylsulfonyl fluoride, and partially by ethylenediaminetetraacetic acid. Hence, the membrane proteins became susceptible to membrane-bound proteinases by oxidative stress. This observation suggests that these membrane-bound proteinases exist to remove oxidatively damaged proteins from the cell membrane. PMID- 7986815 TI - Determination of pathways for sodium movement across corneal endothelial cell derived plasma membrane vesicles. AB - A bovine corneal endothelial cell plasma membrane vesicle preparation was used to investigate passive Na+ transport across the plasma membrane of these cells. Sodium accumulation rate into the vesicle was not dependent on the presence of HCO3- or a HCO3- gradient, but was stimulated by a trans-vesicle pH gradient. Amiloride, furosemide and DIDS all reduced the rate of Na+ accumulation. The data indicate the presence of at least two independent pathways for passive sodium movement across the vesicle: the first probably via a Na+/H+ exchanger and the second a furosemide inhibitable Na+ entry mechanism. No evidence was found for direct Na(+)-HCO3- coupled transport. PMID- 7986816 TI - Activation of plant plasma membrane H(+)-ATPase by the non-ionic detergent Brij 58. AB - Plasma membrane vesicles were purified from tobacco callii and the modulation of H(+)-ATPase by detergents was investigated. The nonionic detergent Brij 58 not only activated ATP hydrolysis (2-fold) but also proton pumping (more than 4 fold). Triton X-100, within a more limited concentration range, produced a similar effect. The simultaneous activation of ATP hydrolysis and proton pumping is not compatible with current interpretations of effects of nonionic detergents on the H(+)-ATPase based on latency of the enzyme and opening of vesicles. PMID- 7986817 TI - Molecular cloning and functional expression of the guinea pig cardiac Na(+)-Ca2+ exchanger. AB - The cDNA of the guinea pig cardiac Na(+)-Ca2+ exchanger was cloned from a lambda ZAP cDNA library. The deduced sequence of the protein corresponds to 970 amino acids and is 98% identical to the canine cardiac exchanger. The leader peptide region shows substantial variation among species. The cloned cDNA can induce Na(+)-Ca2+ exchange activity when in vitro transcribed cRNA is injected into Xenopus laevis oocytes. PMID- 7986818 TI - pO2- and pH-gradients in multicellular spheroids and their relationship to cellular metabolism and radiation sensitivity of malignant human tumor cells. PMID- 7986819 TI - Membrane-dependent reactions in blood coagulation: role of the vitamin K dependent enzyme complexes. PMID- 7986821 TI - Bile acid derived HMG-CoA reductase inhibitors. AB - The target organ for HMG-CoA reductase inhibitors to decrease cholesterol biosynthesis in hypercholesterolemic patients is the liver. Since bile acids undergo an enterohepatic circulation showing a strict organotropism for the liver and the small intestine, the structural elements of an inhibitor for HMG-CoA reductase were combined with those for specific molecular recognition of a bile acid molecule for selective uptake by hepatocytes. Either, the HMG-CoA reductase inhibitors HR 780 and mevinolin were covalently attached to 3 xi-(omega aminoalkoxy)-7 alpha, 12 alpha-dihydroxy-5 beta-cholan-24-oic acids to obtain bile acid prodrugs, or the side chain of bile acids at C-17 was replaced by 3,5 dihydroxy-heptanoic acid--a structural element essential for inhibition of HMG CoA reductase--to obtain hybrid bile acid: HMG-CoA reductase inhibitors. The prodrugs could, as expected, not inhibit rat liver HMG-CoA reductase to a significant extent, whereas the hybrid inhibitors showed a stereospecific inhibition of HMG-CoA reductase from rat liver microsomes with an IC50-value of 0.7 microM for the most potent compound S 2467 and 6 microM for its diastereomere S 2468. Uptake measurements with isolated rat hepatocytes and ileal brush-border membrane vesicles from rabbit small intestine revealed a specific interaction of both classes of bile acid-derived HMG-CoA reductase inhibitors with the hepatocyte and ileocyte bile acid uptake systems. Photoaffinity labeling studies using 3-azi- or 7-azi-derivatives of taurocholate with freshly isolated rat hepatocytes or rabbit ileal brush-border membrane vesicles revealed a specific interaction of bile acid derived HMG-CoA reductase inhibitors with the respective putative bile acid transporters in the liver and the ileum demonstrating the bile acid character of these derivatives, both for the prodrugs and the hybrids. Cholesterol biosynthesis in Hep G2 cells was inhibited by the bile acid prodrugs with IC50-values in the range of 68 nM to 600 nM compared to 13 nM for HR 780 and 130 nM for mevinolin. Among the hybrid inhibitors, S 2467 was the most active compound with an IC50-value of 16 microM compared to 55 microM for its diastereomere S 2468. Preliminary in vivo experiments showed an inhibition of hepatic cholesterol biosynthesis after oral dosage only with prodrugs such as S 3554, whereas the hybrid molecules were inactive after oral application.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 7986820 TI - Mechanism-based inhibition of human leukocyte elastase and cathepsin G by substituted dihydrouracils. AB - A series of dihydrouracil derivatives has been synthesized and investigated for their in vitro inhibitory activity toward human leukocyte elastase (HLE) and cathepsin G (Cath G). Alkyl [sulfonyl(oxy)] uracils 1-2 were found to be efficient, time-dependent inhibitors of elastase (kobs/[I] M-1 s-1 values ranged between 480 and 8110). These compounds formed acyl enzymes that exhibited variable hydrolytic stability which appeared to be dependent on the nature of the R1 group (believed to be accommodated at the primary specificity site, S1). The acyl enzymes formed with cathepsin G deacylated rapidly, leading to a significant regain of enzymatic activity. In sharp contrast, the corresponding phosphorus compounds 3-4 were found to be potent, time-dependent irreversible inhibitors of HLE. Furthermore, the results of the structure-activity relationship studies suggest that the binding modes of compounds 1-2 and 3-4 may be different. PMID- 7986822 TI - The effect of the Z mutation on the ability of alpha 1-antitrypsin to prevent neutrophil mediated tissue damage. AB - Recent studies have shown that alpha 1-antitrypsin (alpha 1-AT) from Z antitrypsin deficiency subjects has a slightly lower association rate constant with neutrophil elastase (NE) than alpha 1-AT from normal subjects, although it is unknown whether this is of clinical importance. We have purified alpha 1-AT from a normal (M alpha 1-AT) and from a deficient (Z alpha 1-AT) subject and have confirmed that the association rate constants for NE are different (5.28; S.E. 0.06.10(7) M-1 s-1 and 1.2; S.E. 0.2.10(7) M-1 s-1, respectively). We have assessed the ability of both of these proteins to inhibit neutrophil mediated fibronectin (FN) degradation in vitro. Both proteins inhibited FN degradation in a dose dependant manner although Z alpha 1-AT was less effective than M alpha 1 AT at equivalent concentrations of active inhibitor (P < 0.05). Inhibition by M alpha 1-AT was 28.5% S.E. 3.9 at 0.01 microM; 35.5% S.E. 7.3 at 0.1 microM and 37% S.E. 8.4 at 0.5 microM, whereas inhibition by Z alpha 1-AT was 9.25% S.E. 3.9; 19.25% S.E. 7.7 and 21.2% S.E. 9.7, respectively. When the time course of inhibition of FN degradation was studied the difference (although less at 1.0 microM) became greater over the 3 h period of the assay. These results suggest that Z alpha 1-AT is less able than the M phenotype to inhibit connective tissue degradation by neutrophils at equivalent concentrations. This is probably due to the lower association rate constant although the reduced stability of the Z molecule may play a role. The differences, together with the reduced plasma concentration, may accentuate the susceptibility of deficient subjects to the development of emphysema. PMID- 7986823 TI - Alterations in intestinal uptake of putrescine and tissue polyamine concentrations in tumor-bearing rats. AB - Intestinal absorption of putrescine and tissue metabolism of polyamines were investigated in rats grafted with the rapidly growing Mat-Lylu prostatic tumor. These animals exhibited a dramatic 21% decrease in weight and protein, but not DNA, content of their intestinal mucosa, relative to healthy rats reared under similarly controlled nutritional conditions. No significant variation in the specific activities of intestinal brush-border membrane enzymes was observed, however, suggesting a comparable differentiation state of intestinal cells exists in both groups. Putrescine uptake by brush-border membrane vesicles prepared from cancerous or healthy rat intestine was a time dependent process at 25 degrees C. Equilibrium uptake was much greater than could be explained by equilibration of the vesicle space with putrescine, indicating that the diamine was bound to membrane sites. Kinetics of putrescine uptake at 2 min revealed that the process involves two components, a saturable Michaelis-Menten carrier and passive diffusion. With respect to the kinetic parameters of putrescine transport, no significant changes were observed between the tumor-bearing and the control rats. After correction for nonspecific binding to the membranes, putrescine accumulation at equilibrium (75 min) was concentration-dependent and fit a single site saturable model. Maximum accumulation of the diamine at equilibrium (Bmax) was increased by more than 46% in the cancerous rats relative to the controls, but the dissociation constant (Kd) was unchanged. Efflux of putrescine from the vesicles was slightly slower in the tumor-bearing group, but the differences were generally not significant. No change was observed with respect to the specific activity of ornithine decarboxylase and the concentration of polyamines in the intestinal mucosa. In Mat-Lylu grafted rats fed a standard diet supplemented with [14C]putrescine, about 19% of body radioactivity was recovered in the tumor within 24 h. This was concomitant with a decrease in the percentage of radioactivity retained in the intestinal, renal and hepatic tissues, relative to that retained in the same tissues of healthy rats. Our findings indicate that the presence of the tumor evolves an adaptive response in the small intestine of the rat, involving an increased capacity of the brush-border membrane to accumulate putrescine. PMID- 7986824 TI - Cloning and analysis of IgM anti-thyroglobulin autoantibodies from patients with Hashimoto's thyroiditis. AB - Hashimoto's thyroiditis is an autoimmune disease in which autoantibodies reactive to a number of thyroid antigens are made. In order to investigate the autoantibody repertoire in this disease, B cells from four patients with Hashimoto's thyroiditis were immortalised and, after limiting dilution, screened for reactivity to thyroid antigens. After a second limiting dilution, one anti thyroglobulin IgM-secreting clone from three patients, and four clones from one patient, were analysed. The Ig heavy and light chain genes from each clone were amplified using the polymerase chain reaction and sequenced. The resulting heavy and light chain sequences were heterogeneous, although the four clones from one patient and the clone from a second patient shared a germline VH sequence. All antibodies had similar functional affinity, comparable to serum IgG from Hashimoto's patients. The cross-reactivity of the antibodies was analysed against bovine and rat thyroglobulin, histones, cardiolipin and human skeletal muscle. The antibodies were polyreactive, indicating that they are probably natural autoantibodies of unknown pathogenic significance. PMID- 7986825 TI - 2-Hydroxyphytanic acid oxidase activity in rat and human liver and its deficiency in the Zellweger syndrome. AB - Phytanic acid is a saturated, branched-chain fatty acid which as a consequence of the presence of a methyl group at the 3-position cannot be degraded by beta oxidation. Instead, phytanic acid first undergoes alpha-oxidation to yield pristanic acid which can be degraded by beta-oxidation. The structure of the alpha-oxidation pathway and its subcellular localization has remained an enigma although there is convincing evidence that 2-hydroxyphytanic acid is an obligatory intermediate. We have now studied the degradation of 2-hydroxyphytanic acid in both rat and human liver. The results show that 2-hydroxyphytanic acid is converted to 2-ketophytanic acid in homogenates of rat as well as human liver. Detailed studies in rat liver showed that the enzyme involved is localized in peroxisomes accepting molecular oxygen as second substrate and producing H2O2. 2 Ketophytanic acid formation from 2-hydroxyphytanic acid was found to be strongly deficient in liver samples from Zellweger patients which lack morphologically distinguishable peroxisomes. The latter results not only provide an explanation for the elevated levels of 2-hydroxyphytanic acid in Zellweger patients but also suggest that the subcellular localization of 2-hydroxyphytanic acid dehydrogenation is identical in rat and man, i.e., in peroxisomes. PMID- 7986826 TI - Effects of Alzheimer's disease-related beta amyloid protein fragments on enzymes metabolizing phosphoinositides in brain. AB - Phosphatidylinositol 4-kinase (PI 4-kinase) and phosphatidylinositol 4-phosphate kinase (PIP kinase) were assayed in membranes prepared from samples of human frontal cortex initially frozen at autopsy. PI 4-kinase activity was significantly lower in Alzheimer's disease patients relative to age-matched controls or patients with Parkinson's disease. PIP kinase was not different in Alzheimer's versus age-matched controls. The beta amyloid protein fragment 1-40 inhibited PI 4-kinase activity in assays of control human or rat cortical membranes. Fragments 1-28 and 25-35 could not mimic the effects of fragment 1-40 while a reverse peptide 40-1 was equipotent. The inhibition of PI 4-kinase by fragment 1-40 was competitive with substrate. The beta amyloid protein fragments had diverse effects on phosphoinositide-specific phospholipase C (PI-PLC) as assayed in rat cortical membranes. Low concentrations of fragment 1-40 stimulated, while high concentrations of 1-40 or 40-1 inhibited PI-PLC activity. Fragment 25-35 stimulated PI-PLC nearly 3-fold, while fragment 1-28 had only minor effects on the enzyme. The results suggest alterations in phosphoinositide metabolism in Alzheimer's disease which could affect signal transduction and/or cytoskeletal organization. PMID- 7986827 TI - Amplification of the H locus in Leishmania infantum. AB - We have selected for a Leishmania infantum cell line resistant to high levels of methotrexate (MTX). The resulting cells were 1233-fold more resistant than wild type and contained amplified H-region circles. Homologous genes to the antifolate resistant ltdh gene and to the P-glycoprotein ltpgpA gene of Leishmania tarentolae were observed to be contained within the amplicon. In order to invoke additional mechanisms of resistance, we examined possible variations in MTX accumulation. Resistance was not correlated with a decreased uptake of MTX. On the contrary, the resistant line presented a 3-fold increase in the steady-state accumulation of drug with regard to the wild-type line. Northern blot analysis using gene specific probes, showed that the ltdh probe and the ltpgpA probe recognized single transcripts of 1 kb and 5 kb respectively which were both overexpressed only approx. 5-fold in resistant cells. We propose that amplification of the antifolate resistance gene, homologue to the ltdh gene of L. tarentolae, is apparently the only mechanism involved in resistance to the cytotoxic drug MTX in L. infantum resistant to 1000 microM of MTX. PMID- 7986828 TI - Vitamin D-dependent rickets type II: regulation of human osteocalcin gene expression in cells with defective vitamin D receptors by 1,25-dihydroxyvitamin D 3, retinoic acid, and triiodothyronine. AB - The vitamin D receptor (VDR) is a nuclear transcription factor which binds to the vitamin D response element (VDRE) of the human osteocalcin gene and regulates its expression. Humans with VDR gene mutations, ever among those with the same point mutation in their VDR gene, demonstrate clinical heterogeneity. In addition, in some patients with these mutations, rickets has not recurred following cessation of therapy during follow-up ranging from 6 to 24 years. While important, it is likely that the VDR protein is not the sole factor in the development of rickets. To try to understand these clinical findings, the complex formed between the VDRE and one or more proteins in the nuclear extracts of cultured skin fibroblasts treated with 1,25-dihydroxyvitamin D-3 (1,25(OH)2D3), retinoic acid (RA), and/or triiodothyronine (T3) was investigated since such complexes are likely to precede the transcription of the VDR gene. Complex formation in the control cells with an intact VDR was increased by treatment with either 0.1 nM, 1 nM, 10 nM 1,25(OH)2D3, 100 nM RA, or 100 nM T3; however, combinations of these compounds did not produce an additive effect. In cells of affected patients, 1,25(OH)2D3, RA, or T3 increased complex formation, while no combination had an additive effect. These results indicate that 1,25(OH)2D3, RA, and T3 play a role in the regulation of bone remodeling through modulating the formation of protein complexes on the VDRE. Therefore, the clinical observations in patients with a VDR mutation might be explained at least in part by the overlapping control of osteocalcin expression by 1,25(OH)2D3, RA and T3. PMID- 7986829 TI - Decreased synthesis and inefficient mitochondrial import of hsp60 in a patient with a mitochondrial encephalomyopathy. AB - In a recent paper (Agsteribbe et al. (1993) Biochem. Biophys. Res. Commun. 193, 146-154) we suggested deficiency of heat shock protein 60 (hsp60) as the possible cause of a systemic mitochondrial encephalomyopathy with multiple deficiency of mitochondrial enzymes. In this paper we present new data which strongly support this hypothesis. Hsp60 deficiency appeared to be not a common side effect of impaired mitochondrial metabolism as eight out of ten fibroblast cultures from patients with systemic mitochondrial myopathy contained normal quantities of the protein. The low steady state amount of hsp60 in the fibroblasts of our patient is caused by decreased synthesis of the protein and not by its enhanced degradation indicating that the hsp60 deficiency is indeed a primary defect. Processing of hsp60 but not of other mitochondrial proteins is markedly retarded in the patient cells. Other functional properties of the patient hsp60 like the assembly of hsp60 monomers to the native 14mer complex and the affinity of this complex to denatured protein are not impaired. Our results underline that a primary defect in hsp60 synthesis and/or processing causing a low steady state amount of hsp60 is the molecular basis of this mitochondrial disorder. The presented data provide for the first time substantial evidence that deficiency of a heat shock protein can give rise to pathological conditions in man. PMID- 7986831 TI - Analysis of 11-dehydrothromboxane B2 in human urine improved by use of gas chromatography/high-resolution selected ion monitoring with 18O2-labelled analogue as an internal standard. AB - Gas chromatography/high-resolution selected ion monitoring (GC/HR-SIM) for the determination of 11-dehydrothromboxane B2 (11-dehydro-TXB2) in human urine is described. Combined use of the lactone ring opening reaction and dimethylisopropylsilylation has been adopted for the analysis of 11-dehydro-TXB2, to give a new chemically stable derivative. The feasibility of using this derivative for the analysis of 11-dehydro-TXB2 in human urine has been evaluated. Following the addition of 18O2-labelled analogue, for use as an internal standard, the samples were extracted using chromatographic separation with Bond Elut C18 and silica gel. Derivatization of the extracted 11-dehydro-TXB2 was followed by GC/SIM at resolution of 5000. This method enables selective detection of 11-dehydro-TXB2 in human urine without serious interference from other endogenous substances. In 11 volunteers, the mean urinary excretions of 11 dehydro-TXB2 was 547.6 +/- 217.6 ng per day. PMID- 7986830 TI - Fragmentation characteristics of neuropeptides related to chromogranin B and proenkephalin B using fast atom bombardment and collision-induced dissociation. AB - This study deals with the mass spectral characterization of selected neuropeptides related to chromogranin B and proenkephalin B precursor proteins using fast atom bombardment (FAB) ionization in combination with low- and high energy collision-induced dissociation. Fragmentation pathways were investigated using linked scan and tandem mass spectrometric techniques. First-order FAB mass spectra and product ion spectra of [M+H]+ ions are discussed and analysed for structure-specific information. In the high-energy product ion spectra, abundant y and c ions are found to be indicative of the presence of proline and threonine residues, respectively. With regard to side chain specific ions, diagnostic d and w ions are found, which support the presence of leucine, glutamic acid and glutamine at specific positions in the amino acid sequence. PMID- 7986832 TI - Determination of xanomeline in human plasma by ion-spray tandem mass spectrometry. AB - Xanomeline is a muscarinic receptor agonist currently in phase II clinical trials for the treatment of Alzheimer's disease. A fast, sensitive and specific assay has been developed to determine xanomeline plasma concentrations using ion-spray tandem mass spectrometry. Xanomeline and a structural analog, LY282122, were extracted from basifed plasma into hexane. The dried hexane extracts were reconstituted and injected onto a 10 x 1 mm C18 reversed-phase column. A mobile phase of 33 mM ammonium acetate and 0.33% acetic acid in 30/70 (v/v) water acetonitrile was pumped through the column at 50 microliters min-1. The mobile phase eluant was introduced directly into the ion-spray interface. The mass spectrometer was operated in the positive ion mode for specific detection of the product ions of xanomeline and the internal standard. The method has a linear range of 0.075-5.0 ng xanomeline per milliliter of plasma. Sample run times were 2.5 min from one injection to the next. PMID- 7986834 TI - Quantitative measurement of amphetamine in human plasma by gas chromatography/negative ion chemical ionization mass spectrometry using (2H5)amphetamine as internal standard. AB - A selected ion monitoring stable isotope dilution gas chromatographic/negative ion chemical ionization mass spectrometric assay for amphetamine in human plasma is described. The preparation of (2H5)amphetamine from the intact target molecule and its use as an internal standard for quantitative gas chromatography/mass spectrometry are demonstrated. Derivatization to the highly electrophoric pentafluorobenzoate with pentafluorobenzoyl chloride in hexane resulted in high yield of prominent negative ions with methane as a moderating gas. The pentafluorobenzoate was also found to be superior to fluoroacyl derivatives with respect to sample handling due to its lower volatility. The method presented permits detection of amphetamine in the low picogram per millilitre range and should thus be highly useful for its trace level determination in forensic, toxicological and pharmaceutical applications. PMID- 7986833 TI - Metabolism of cycloate in radish leaf: metabolite identification by packed capillary flow fast atom bombardment tandem mass spectrometry. AB - The metabolism of cycloate, a thiocarbamate herbicide, was investigated in mature radish leaf. Twelve new metabolites were identified by liquid chromatographic/mass spectrometric analysis using fast atom bombardment and packed capillary liquid chromatography columns. Full-scan and tandem mass spectrometric methods were employed. Application of the on-column focusing technique resulted in identifications with injections of as little as 15 ng of metabolite (20 ppb in radish). This injection technique allows the practical use of packed capillary liquid chromatography/mass spectrometry in sample-limited applications. Cycloate is oxidized to several ring-hydroxylated isomers that are subsequently glucosylated and esterified with malonic acid. Cycloate is also conjugated with glutathione. Metabolic hydrolysis of the glutathione conjugate formed a cysteine conjugate that is further metabolized by amidation with either malonic or acetic acid. Transamination of the cysteine conjugate gave a thiolactic acid derivative. Metabolites were also identified that were the result of both ring-hydroxylation and conjugation with glutathione. One of these, an N acetylcysteine conjugate, is the first report of a mercapturic acid in plants. The structures of two of the new metabolites were confirmed by chemical synthesis. PMID- 7986835 TI - [Radiology of cerebrovascular malformations]. AB - Cerebral vascular malformations are, after hypertension, the second most frequent cause of non-traumatic, intracerebral hemorrhage. A reliable intravital diagnosis only became possible with radiological diagnostic methods which also contributed significantly to the development of therapeutic concepts. Diagnostic and therapeutic possibilities for the various forms of cerebral vascular malformations are surveyed in the present review. Since radiology occupies a central position in the diagnosis and (in the meantime also) therapy of cerebral vascular malformations, epidemiological and prognostic factors are also discussed in detail. PMID- 7986836 TI - [Magnetic resonance tomography diagnosis of the posterior chamber lens]. AB - Intraocular lenses were investigated by MRI to obtain information about the quality of this method. In experimental studies, seven lenses of between 0 and 30 diopters were visualized. By MRI it was possible to differentiate the various diameters of lenses. It was not possible to discriminate the material of the intraocular lenses. After these first studies the eyes of two corpses and eight patients were investigated. Because of the resolution of MRI it was possible to tell the diopter of implanted lenses. However, by use of MRI in the regular position, a tilting or decentration of the intraocular lens was demonstrated. PMID- 7986837 TI - [Optimizing intravenous bolus contrast medium injection in cervical CT diagnosis]. AB - PURPOSE: A prospective, comparative study of 60 patients for optimizing contrast medium (CM) administration for spiral CT of the neck. METHODS: Prior to the investigation, the patients were randomly assigned to three groups (n = 20 each): a) conventional CT technique, interscan duration 10 s, CM volume 150 ml of Ultravist 300 (30 ml at a flow rate of 1.5 ml/s, the remaining 120 ml as maintenance dosage of 0.5 ml/s); b) so-called dynamic CT technique, interscan duration 5 s, CM volume 100 ml (200 ml at a flow rate of 2 ml/s and 80 ml with a flow rate of 0.5 ml/s); c) spiral CT technique, total investigation time to store the crude data was 30 s, a CM dosage of 50 ml at a flow rate of 2 ml/s (30 ml) in the first phase and 0.7 ml/s (20 ml) in the second phase was studied. RESULTS: The current evaluation of the CM time-density course, image quality, diagnostic efficiency, and investigation time showed that a good to very good contrast medium enhancement of the neck vessels was achieved in all groups so that pathological findings were well differentiated. CONCLUSIONS: The CM volume could be reduced to a third of the original used amount without loss of diagnostic security by use of the spiral CT technique. PMID- 7986838 TI - [Iomeprol: results of clinical trials with a new nonionic contrast medium in children]. AB - PURPOSE: To assess the tolerability of the newly developed nonionic contrast medium Iomeprol in pediatric patients. MATERIAL AND METHODS: A total of 438 patients (1 day-17 years) were enrolled in open-label phase III studies with Iomeprol in the most important radiologic, urologic, and cardiologic indications. Iomeprol was tested in five concentrations ranging from isotonic solutions of 150 mg iodine/ml up to 400 mg iodine/ml. Half of the patients were younger than 3 years. RESULTS: Apart from the mostly slight sensations of heat, pain, and taste, the following adverse events were observed independently of a causal relationship to the test compound: vomiting (1.8%), rise in blood pressure (1.8%), and restlessness (1.1%). The respective incidence of all other adverse events was below 1%. CONCLUSION: Iomeprol is a suitable and well-tolerated nonionic contrast medium for use in pediatric examinations. PMID- 7986839 TI - [Magnetic resonance tomography and computerized tomography of Wegener's granulomatosis of the orbits]. AB - Of a total of 121 patients with histological proven Wegener's Granulomatosis, orbital involvement occurred in 12 cases. Eight of them underwent magnetic resonance imaging (MRI) of the head and brain, in 2 cases computed tomography (CT) was additionally performed. With MRI orbital granulomas had a low signal intensity in T1- and T2-weighted spin-echo sequences. After i.v. contrast medium administration an inhomogeneous enhancement was found. Because of the multiple imaging planes and high soft tissue contrast, orbital granulomas were better delineate with regard to the intraorbital muscles and the optic nerve using MRI than with CT. Osseous destruction and sclerosis of the orbital walls were demonstrated more effectively using CT. MRI and CT are thus complementary for diagnosing and staging, of orbital granulomas and periorbital involvement in Wegener's Granulomatosis. PMID- 7986840 TI - [Computerized tomography of kidney tumors]. AB - Among 220 renal tumors which we detected by computed tomography, there were 168 renal cell carcinomas, 24 tumor of the renal pelvis, 16 angiomyolipomas, 6 Wilms tumors, 3 oncocytomas, one liposarcoma, one mesenchymal tumor, and one rhabdomyosarcoma. Computed tomography had the highest accuracy of the diagnostic procedures with a sensitivity of 99.5% and a specificity of 98%. 83% of the renal cell carcinomas showed signs of malignancy in computed tomography; the staging of the renal tumors by computed tomography was correct in 67% of the cases. The diagnostic value of other diagnostic tools (sonography, urography, angiography, cavography) of renal tumors is discussed in terms of our own results. PMID- 7986841 TI - [Xenon computerized tomography of kidney transplants]. AB - Xenon-CT is an established method for determining cerebral perfusion, while applications in other organs are rare. We evaluated the diagnostic potential of measuring the regional Renal Blood Flow (rRBF) in 10 patients with transplanted kidneys by xenon-CT. We found significant differences in the rRBF between the renal medulla and the cortex. There were no differences between normal renal transplants and transplants with chronic rejection. PMID- 7986843 TI - [Lateral urethrocystography in digital subtraction technique]. AB - The first application of the digital subtraction technique to lateral urethrocystography is described. This methodology facilitates gynecological urological operations by providing reliable investigation results and an unambiguous image interpretation. Methods and first experiences with the digital subtraction technique in gynecological-urological diagnosis are reported. PMID- 7986842 TI - [Results of selective kidney DSA in suspicious computerized tomography findings- retrospective evaluation of 122 cases]. AB - The superiority of computer tomography in the detection and staging of renal malignomas has been proven in numerous studies. In this retrospective analysis, the significance of the pre-surgically still widely and routinely performed, selective kidney angiography was investigated. The written computer tomographical and angiographic findings of 122 patients were classified according to malignancy stage urgency. They were then compared to progression, and surgical finding respectively. Angiography had the greatest influence on the therapeutic procedure in those patients having only a slight computer-tomographical suspicion of tumor. An operation was waived by 12 patients. A small hypernephroma (pT 2 showing typical tumor vessels was found in two patients. Inoperability excepted, a surgical denudation was performed in all patients with computer tomographical tumor typical, or suspicious finding, irrespective of the angiographic result. The diagnosis was surgically confirmed in all patients having a tumor-specific angiogram. Yet besides benign tumors, 4 hypernephromas and 5 other malignomas were found in those patients showing an angiographically classified, vessel-free formation. PMID- 7986844 TI - [Percutaneous aspiration thromboembolectomy in the treatment of acute occlusion of the lower leg arteries]. AB - Percutaneous aspiration thrombembolectomy (PAT) is a very suitable method for the recanalization of the popliteal and lower limb arteries after embolic occlusion. In thrombotic occlusion in patients with arteriosclerotic disease, PAT can easily be combined with other interventional procedures, yielding good results. With the use of PAT the dose of regionally effective fibrinolytic drugs, which may be additionally administered, can be significantly reduced. PMID- 7986846 TI - [Stereotactically guided histologic punch biopsy of the breast in comparison with stereotactically guided cytologic puncture]. AB - Stereotactic large-core biopsy provides better results in comparison to stereotactic cytologic fine-needle aspiration. Good results arise in 92.52% of the cases; that is 13.17% better than fine-needle aspiration. Technique and indication of the cases are described. PMID- 7986845 TI - [Radiology in the 3d World, illness, hunger, violence]. AB - Parasitoses, perinatal X-ray diagnostics, hunger, war, and torture produce X-Ray findings that are hardly known in Western and Central Europe. X-ray diagnostics in the 3rd world are often decisive for the diagnosis due to the lack of other methods. X-ray diagnostics offers many possibilities but is often not available or available only for few. PMID- 7986847 TI - [Change in the glandular bodies of the breast after hormone therapy. Observations from the radiologic viewpoint]. AB - In the last few years we have recognized a clear change in the mammograms in women undergoing hormone replacement therapy. Not all of them reacted in the same way: 30% on 366 treated patients showed a distinct glandular hyperplasia. Some developed nodes like cysts or adenomas, others had an increase in calcification as a sign of epithelia proliferation, as verified by histological examination. The opposite effect was seen in women receiving antioestrogen therapy as a consequence of breast-conserving therapy. The problems will be illustrated. PMID- 7986848 TI - [Intracystic, proliferating papilloma of the breast in a man]. AB - The case of a male patient with a rapidly developing breast tumor is described. Histology demonstrated and intracystic, proliferating papilloma. Mammography, sonography, an magnetic resonance imaging further substantiated the clinical findings. PMID- 7986849 TI - [Isolated fracture of the trochlea humeri following direct elbow trauma]. AB - Isolated fractures of the Trochlea humeri are only rarely seen because in case of indirect trauma this portion of the elbow is only partially exposed to transmitted forces and in case of direct injury adjacent elements are also involved. On the lateral films a half-moon shaped fragment in front of the Humerus together with joint effusion are indicative of this type of fracture. Depending on the grade of dislocation of the fragment, which has to be shown radiologically, conservative or operative management are chosen. PMID- 7986850 TI - [Lung findings in filariasis]. AB - A solitary intrapulmonary mass, found accidentally, demands further investigations to assure the diagnosis. Even if we are unable to give an exact diagnosis, we should try to determine the character of the lesion; often the clinical findings can be helpful. If this is not the case, further possibilities to arrive at the correct diagnosis should be indicated. PMID- 7986851 TI - [Safety in parenteral nutrition mixtures]. PMID- 7986852 TI - [The outlook for hormonal therapy in nutrition]. AB - When the supply of energetic substrates is insufficient to slow the development of the catabolism, the next step is to focus on the neuro-endocrine mechanism which regulates the anabolism-catabolism balance. In this work, we review the endocrine response to stress and its implications in protein metabolism, in order to evaluate the different therapeutic possibilities available. Pharmacological blocking of the secretion of catabolic hormones (glucagon and catecholamines) has been unsuccessful up to now. Insulin is the only hormone which produces anabolism in all energetic substrates, but the results published about its administration with glucose and amino acids and its effects upon the nitrogen balance are controversial. The administration of anabolic steroids such as nandrolone, stanolone, and methenolone are usually associated with protein anabolism with minimum androgenizing action. The most recent works lead to the study of the effects of the use of GH and IGF-1 with clearly hopeful results. We have not yet acquired enough experience to use these methods in the habitual clinical practice. At the moment, the clinical studies are in the experimental stage and their application in nutrition is not accepted by the official authorities. PMID- 7986853 TI - [Major abdominal surgery and the clearance of lipid emulsions]. AB - The use of lipid emulsions for TPN remains controversial. Although experimental studies show that medium chain triglycerides (MCT) are beneficial over long chain triglycerides (LCT) clinical studies are contradictory. With the aim to study the clearance of two lipid emulsions a prospective study was designed. 21 patients, submitted to resective surgery because of upper gastrointestinal tract malignancy were randomized in three groups. In group I (without lipids): all caloric intake was supplied by hypertonic glucose solution. In group II (LCT group) 55% of caloric intake was supplied by glucose and 45% by a LCT 20% emulsion (Intralip[id 20%, Kabi-Pharmacia). In group III (MCT group) 55% of caloric intake was supplied by hypertonic glucose solution and 45% by a physical mixture of LCT and MCT at 20% concentration (Lipofundina MCT, B. Braun). Our results show that in postoperative period of major abdominal surgery both lipid emulsions are cleared of in a similar way. When these emulsions are administered during 12 hours per day plasmatic triglycerides are completely cleared before to start the next-day infusion of lipid emulsion. Differences in total cholesterol were not found between groups. Nevertheless LDL-cholesterol rose significatively between first and tenth postoperative day in LCT group. PMID- 7986854 TI - [The behavior and utility of 3-methylhistidine, urinary urea excretion and the creatinine height index in the sepsis patient]. AB - We have studied in a prospective manner the evolution of three urinary indices which measure protein catabolism: 3-methylhistidine, the creatinine level index, and the excretion of urinary nitrogen, the latter being calculated based on the excretion of urea in urine. These studies have been performed using healthy patients only being given parenteral nutrition. Our data shows a very significant decrease in 3-methylhistidine (p = 0.001) and in the excretion of nitrogen calculated (p = 0.026), there being a correlation among the differences between these two parameters. PMID- 7986855 TI - ["All in one" parenteral nutrition: is it that safe?]. AB - The use of "all in one" admixtures is supported by an extensive number of studies and by many years of experience. However, we detected stability problems in some mixtures whose stability was previously reported. We made modifications in one of these mixtures [composed of 1.000 ml Freamine 8.5%, 100 ml 10% dextrose, 500 ml water, 500 ml Intralipid 20%, 75 ml electrolyte solution (Na 75 mEq, K 60 mEq, Ca 15 mEg, Mg 15 mEq, Cl 90 mEq, acetate 75 mEq)] in order to see how the different components affect the emulsion stability. All the admixtures were visually inspected after storage during 24 hour at room temperature. It was observed that admixtures with low glucose concentration, high electrolyte levels and high volume were less stable than admixtures containing high glucose, low electrolyte and low volume. Amino acid concentration did not increased the stability as expected. MCT/LCT emulsions were more stable than LCT emulsions. More studies are needed to explain the stability problems of these TPN solutions. PMID- 7986856 TI - [Lymphocyte subpopulations and surgery. The role of postoperative parenteral nutrition]. AB - The effects of LCT-based lipid emulsions used in TPN on immune system remains controversial. In this prospective study we research the effects of three types of TPN on T-lymphocyte subsets and NK cells. 21 patients diagnosed because of upper gastrointestinal carcinoma (UGIC), and amenable of curative surgery were included in the study. TPN support was maintained 10 postoperative days at least. All patients received 35 non-proteic Kcal/KG BW/day. Group I (without lipid): received 100% of caloric intake (CI) by glucose. Group II (LCT): received 55% of CI by glucose and 45% by LCT at 20% emulsion. Group III (MCT/LCT): received 55% of CI by glucose and 45% by MCT/LCT at 20% mixture. T-lymphocyte subsets were determined by flow cytometry preoperatively and in first and tenth postoperative days. Our results suggest that patients diagnosed of UGIC present alterations of cellular immunity. These alterations are increased by the age and by surgical act. The changes found are independent of the type of TPN. LCT-based emulsions have similar effects on T-lymphocyte subsets that MCT/LCT-based emulsions. PMID- 7986857 TI - [The percutaneous retrieval of vascular foreign bodies]. AB - Intravascular foreign bodies can cause significant complications: thrombosis, pulmonary and peripheral embolism, etc. It is therefore necessary to remove them, and this may be accomplished through surgery or by means of radiotherapy techniques. In the past year we have percutaneously extracted three foreign bodies originating in vascular access pathways. PMID- 7986859 TI - Studies of seasonal patterns in reproductive failures. PMID- 7986858 TI - [A practical nursing guide for the planning and evaluation of the care of the patient with domiciliary parenteral nutrition. The planning of patient care with DPN]. AB - We present a proposal for the planning of nursing care for the patient with home parenteral nutrition (HPN). In this proposal the problems, goals, and actions to be taken by the nurse are defined. In this working guide, it is explained what the diverse aspects are that the nurse taking care of a patient with HPN needs to know, as well as the care to be given and the evaluation of the same, in order to insure that the patient with HPN is given a good preparation in his self-care, giving the patient an acceptable degree of independence and quality of life, as well as a lower risk of complications. PMID- 7986860 TI - National policy, social conditions, and the etiology of maternal mortality. PMID- 7986861 TI - Is there a seasonal pattern in risk of early pregnancy loss? AB - We recruited 221 women with no known fertility problems who were discontinuing contraception to conceive a pregnancy. The primary objective of this prospective study was to estimate the incidence of very early pregnancy loss by using a highly sensitive and specific assay to detect the pregnancy hormone chorionic gonadotropin in first morning urine specimens. We found the risk of early pregnancy loss, defined as loss within 6 weeks of the last menstrual period, to vary by season of conception, with a large amplitude and some consistency across the 3 years of the study. Such a seasonal pattern may reflect the contribution of an environmental factor that varies with season. The peaks in risk ranged from early September to early December. A seasonal pattern of early pregnancy loss should contribute to a corresponding lagged seasonal pattern in livebirths. Accordingly, we looked for corroborative evidence in regional birth data from the same years. There was some correspondence, but this was largely limited to the first year of the study. PMID- 7986862 TI - Maternal deaths among women with pregnancies outside of family planning in Sichuan, China. AB - To assess the impact of family planning status on maternal mortality, we analyzed data gathered in a community-based, maternal mortality surveillance study conducted by the Sichuan Health Department in the People's Republic of China during 1989-1991. The overall maternal mortality ratio, which included only deaths of pregnant women within family planning guidelines ("planned" pregnancies), was 78.9 per 100,000 livebirths. When the deaths of pregnant women outside of family planning ("unplanned" pregnancies) were included, the maternal mortality ratio doubled to 135.6 per 100,000 livebirths. The leading causes of death for women with "planned" and "unplanned" pregnancies were the same: hemorrhage, postpartum infection, pregnancy-induced hypertension, cardiac diseases, and pulmonary diseases. As among women with "planned" pregnancies, about 40% of maternal deaths among women with "unplanned" pregnancies occurred at home, and 20% occurred en route to a hospital. After controlling for the confounding effects of gravidity and education, the odds ratio of maternal death associated with "unplanned" pregnancy status was 2.6 [95% confidence interval (CI) = 2.0-3.7], which declined to 2.0 (95% CI = 1.4-2.9) with additional control for the effect of prenatal care visits. Our study indicates that women with "unplanned" pregnancies have a higher risk of maternal death, which is only partially attributed to less prenatal care. PMID- 7986864 TI - Magnetic fields, leukemia, and central nervous system tumors in Swedish adults residing near high-voltage power lines. AB - We conducted a case-control study to test the hypothesis that exposure to magnetic fields of the type generated by high-voltage power lines increases the incidence of leukemia and central nervous system tumors in adults. The study was based on people who, between 1960 and 1985, had lived on a property in Sweden located within 300 meters of 220 or 400 kilovolt power lines. We identified a total of 325 leukemia cases and 223 cases of central nervous system tumor. Two matched controls per case were selected at random. We assessed exposure by spot measurements and by calculations of the magnetic fields generated by the power lines. For calculated magnetic field levels of 0.2 microT or more closest in time to diagnosis, we found an elevated relative risk (RR) for acute myeloid leukemia [RR = 1.7; 95% confidence interval (CI) = 0.8-3.5] and chronic myeloid leukemia [RR = 1.7; 95% CI = 0.7-3.8]. Using cumulative exposure for the 15 years preceding diagnosis, we found relative risk estimates for acute and chronic myeloid leukemia of 2.3 (95% CI = 1.0-4.6) and 2.1 (95% CI = 0.9-4.7), respectively, for the highest exposure category. For chronic lymphatic leukemia and for central nervous system tumors, relative risk estimates were close to or below unity. PMID- 7986865 TI - Varied forms of bias due to nondifferential error in measuring exposure. AB - Continuous exposure variables are frequently categorized in epidemiologic data analysis. It has recently been shown that such categorization may transform nondifferential error in measuring continuous exposure variables into differential exposure misclassification. This paper assesses the direction and magnitude of the resulting misclassification bias under a variety of practically relevant forms of nondifferential measurement error. The expected bias of measures of the exposure-disease association is toward the null in the case of purely random measurement error with a mean of zero. Systematic nondifferential over- or underestimation of the exposure may bias measures of the exposure disease association either toward the null or away from the null, depending on the underlying distribution of exposure, the true exposure-disease relation, and the cutpoints employed for categorization. If exposure measurement error has both random and systematic components, the direction of the net bias is less predictable than with pure error of either type, but bias toward the null is increasingly likely as the random component grows larger. The results indicate the need for careful evaluation of potential effects of nondifferential exposure measurement error in epidemiologic studies in which categories are formed from continuous exposure variables. PMID- 7986863 TI - Social functioning and overall mortality: prospective evidence from the Kuopio Ischemic Heart Disease Risk Factor Study. AB - We studied the associations between 11 scales of social functioning and risk of death over an average follow-up time of 71 months in 42- to 60-year-old men in the Kuopio Ischemic Heart Disease Risk Factor Study. In age-adjusted analyses, men were at increased risk of death if they reported few persons to whom they gave or received social support, nonparticipation in organizations, low quality of social relationships, a small number of friends, or not currently being married. Frequency of interaction, shyness, and use of emotional support when troubled were not associated with risk of death; the use of instrumental support when troubled was associated with increased risk. There was little evidence of confounding of these associations by the presence of 31 chronic or acute conditions, perceived health status, or six risk factors. Consistent associations were found in a healthy subgroup. These data add to the growing body of literature linking mortality risk with social functioning, especially in relation to organizational participation and quality of relationships. PMID- 7986866 TI - Limitations of the correlation coefficient in the validation of diet assessment methods. CODIAB-INSERM-ZENECA Pharma Study Group. AB - Dietary assessment methods usually are validated one against the other, using the correlation coefficient between the methods to assess agreement. The correlation coefficient, however, is only an indicator of relative agreement and depends on the range of intakes. As this dependence can lead to misinterpretation, we propose that the standard deviation of the difference between methods should be used as an indicator of absolute agreement and the standard deviation of their average as an indicator of the range of intakes. We illustrate this method in a validation study of a diet history against a 3-day diet record in 58 non-insulin dependent diabetes mellitus patients. A re-analysis of studies from the literature validating food frequency questionnaires against diet records showed that the absolute agreement between methods is very consistent and that the differences in the correlation coefficients are mostly due to the selection of subjects. PMID- 7986867 TI - Smoking, obesity, alcohol consumption, and the risk of rheumatoid arthritis. AB - There is some evidence that sex hormones may influence the incidence of rheumatoid arthritis. Obesity has been found to increase endogenous estrogens, particularly among postmenopausal women. Although the association of endogenous hormones with smoking and alcohol use is less clear, we examined the relation of these three factors with rheumatoid arthritis in women. We conducted a population based case-control study of rheumatoid arthritis in King County, WA, and Group Health Cooperative of Puget Sound. We compared 349 incident cases of rheumatoid arthritis with 1,457 controls selected by random digit dialing or by random selection from the enrollment files of Group Health Cooperative. We conducted personal interviews to collect data on weight, smoking, alcohol history, reproductive variables, and other demographic variables. Women with 20 or more pack-years of smoking had a relative risk of 1.5 [95% confidence interval (CI) = 1.0-2.0] compared with never-smokers. Post-menopausal women who averaged more than 14 alcoholic drinks per week had a reduced risk of rheumatoid arthritis (relative risk = 0.5; 95% CI = 0.2-1.7). Women in the highest quartile of body mass index had a risk of 1.4 (95% CI = 1.0-2.0) relative to women with lowest body mass index. PMID- 7986868 TI - Alcohol drinking and prevalence of self-reported gallstone disease in the 1983 Italian National Health Survey. AB - We studied the relation between alcohol drinking and gallstone disease, using data from the 1983 Italian National Health Survey. This survey included information on 58,462 adults age 25 years and over (27,912 males and 30,550 females), randomly selected within strata of geographical area, size of the municipality of residence, and size of the household. The prevalence of gallstone disease or cholecystectomy was 2.4% among males and 4.8% among females. Compared with alcohol abstainers, the relative risk of gallstone disease, controlling for age, sex, education, smoking, and body mass index, was 0.83 [95% confidence interval (CI) = 0.73-0.92] for occasional and regular moderate drinkers (< 25 ml of ethanol per day), 0.67 (95% CI = 0.59-0.77) for intermediate drinkers (25-50 ml per day), and 0.58 (95% CI = 0.47-0.70) for heavy drinkers. This inverse association was consistent across strata of age, sex, and body mass index. PMID- 7986869 TI - Correlates of decaffeinated coffee choice. AB - We sought to identify the illness risk factors associated with consumption of decaffeinated coffee in a sample of 2,677 adults. Women who drank decaffeinated coffee exclusively were more likely than other women to consume vitamin supplements and cruciferous vegetables, to use seat belts routinely, and to exercise regularly. Among men, those who drank decaffeinated coffee exclusively were more likely than others to have a low body mass index and to consume a low fat diet and cruciferous vegetables. We conclude that people who drink decaffeinated coffee differ from others in ways that might provide information about the risk of illnesses. PMID- 7986870 TI - Internal validation of Medicare claims data. AB - The Medicare database is commonly used for epidemiology and health services research, but validation of its data by chart review or questionnaire may be difficult and expensive. Since hospital and physician bills are independent in Medicare, however, these two data sources can be used to supplement and corroborate each other. This "internal validation" is illustrated here for hip fracture and prostatectomy. Agreement of the hospital and physician data streams regarding site of hip fracture (neck vs other), treatment of hip fracture (internal fixation vs arthroplasty), and type of prostatectomy (transurethral resection of prostate, open, or radical) was excellent, with percentage of agreement generally between 89% and 99%, and kappa statistics typically between 0.74 and 0.95. When validation with outside data sources is not readily available, such internal validation of Medicare data may be valuable. PMID- 7986871 TI - Reliability of information on chronic disease risk factors collected in the Missouri Behavioral Risk Factor Surveillance System. AB - The Behavioral Risk Factor Surveillance System (BRFSS) is widely used by state health agencies to measure the prevalence of chronic disease risk factors. We completed a test-retest study to assess the reliability of the Missouri Behavioral Risk Factor Surveillance System. We conducted telephone reinterviews for 222 respondents of completed Behavioral Risk Factor Surveillance System interviews from March and April 1993. The second interview was completed between 6 and 30 days after the first interview. Agreement was high for sociodemographic variables (kappa values from 0.85 to 1.00). Reliability of information on chronic conditions and risk factors was also high, with kappa values from 0.82 for hypertension to 1.00 for current smoking status. Regarding cancer screening practices, reliability was lower for knowledge of the prostate-specific antigen test (kappa = 0.21) than for women's cancer screening practices (that is, the mammogram and Papanicolaou smear). Questions on attitudes toward environmental tobacco smoke showed lower reliability than did questions on individual actions to reduce exposure to environmental tobacco smoke. PMID- 7986872 TI - In defense of black box epidemiology. PMID- 7986873 TI - The emptiness of the black box. PMID- 7986874 TI - The effect of age at smoking initiation on lung cancer risk. PMID- 7986875 TI - Should an expected number of cases be an integer? PMID- 7986876 TI - The influence of occupational activity on the menstrual cycle and fecundability. PMID- 7986877 TI - Indian and Native communities realize the extent of military service touches the lives of this special population. PMID- 7986878 TI - Warriors all. PMID- 7986879 TI - The national survey of Indian Vietnam veterans. AB - Largely through the efforts of Harold Barse and Frank Montour, Readjustment Counseling Service, a division of the U.S. Department of Veterans Affairs, formed a working group to deal with the simple lack of information on Indian Vietnam veterans. Barse is founder of the Vietnam Era Veterans Inter-Tribal Association and a counselor for the Oklahoma City, Oklahoma, Vet Center. Montour is a Vet Center counselor in Lincoln Park, Michigan. PMID- 7986881 TI - A cultural and community process. PMID- 7986880 TI - Stress, depression, substance abuse, and racism. AB - Many studies have focused on the special needs of American Indian populations. Some of these studies have special impact on Indian veterans. These can be grouped for consideration around cultural and personal identity problems. These problems are multifaceted and interacting. They bear directly on the community and individual self-esteem. The four major points of these problems are stress, depression, alcohol/drug dependence, and racism. PMID- 7986882 TI - American Indian veterans and families. PMID- 7986883 TI - Lessons from child of water. AB - This chapter examines the perceptions and treatment of psychological combat reactions by American Indians. My goal is to provide the reader with an introduction to the clinical implications of these perceptions and treatment in order to encourage a closer examination of what American Indian healers have to offer mental health professionals trained in the mainstream (what I will refer to as Anglo) psychological tradition. To do this we shall briefly examine how American Indians regard war and the role of warriors, for this cultural perception influences how combat reactions such as posttraumatic stress disorder symptoms are perceived and treated. Regardless of the value of what we might learn from American Indian culture, it does not matter what they say if we will not hear. It is necessary to consider attitudes typically held toward the concepts and techniques of American Indian healing practices if we wish for this examination to be more than an anthropological exposition, and have clinical value for Anglo mental health professionals. PMID- 7986884 TI - Metabolism and chirality in psychopharmacology. PMID- 7986885 TI - Shortened REM latency PostECT is associated with rapid recurrence of depressive symptomatology. AB - Electroconvulsive therapy (ECT) is highly effective in the treatment of major depressive disorder (MDD). The 1-year relapse rates are reported to be high and in the 30%-60% range, however. To test whether polysomnography (PS) can identify patients with a propensity for relapse we studied 20 patients, responders to a course of ECT, with PS studies. All patients met baseline diagnostic criteria for MDD, were treated with ECT following standardized protocols, had PS studies performed after the course of ECT in a medication-free state, received maintenance antidepressants postECT, and were followed periodically with phone interviews. The recurrence of depressive symptoms was determined at 3 months and 6 months after discharge. Fifty-five percent of the patients were symptomatic when evaluated 6 months after the ECT. Sleep Onset rapid eye movement (REM) periods were identified in 55% of the patients. As a group, patients who had experienced a recurrence of depressive symptoms by 6 months after discharge, had significantly shorter REM latencies after the course of ECT. A shorter REM latency after ECT identified patients who at six months demonstrated significant depressive symptomatology. Shortened REM latency after ECT in patients with MDD appears to be a correlate of vulnerability for relapse. PMID- 7986886 TI - A linkage study of distal chromosome 5q and bipolar disorder. AB - There are well-established abnormalities of hypothalamic-pituitary-adrenal (HPA) axis and beta 2 adrenergic receptor function in affective disorders. The genes for the glucocorticoid receptor (GRL) and the beta 2 adrenergic receptor (ADRB2) have been cloned and mapped to distal chromosome 5q. In this study, we have examined polymorphisms of these two candidate genes and other nearby markers for linkage to bipolar disorder in Amish pedigree 110 and three large Icelandic pedigrees. These loci were tested for linkage in two-point and multipoint analyses using a model of autosomal dominant transmission with age-dependent reduced penetrance. Two-point analyses revealed a maximum LOD score of 1.14 at theta = 0.20 from GRL. Linkage could be excluded to ADRB2, as well as to three nearby anonymous markers, D5S207, D5S70, and D5S119. Analyses of another anonymous marker, D5S36, were inconclusive. Multipoint analyses excluded linkage to a 55 cM region including the interval between D5S207 and D5S36 and flanking regions, with the exception of a 7 cM interval between GRL and ADRB2. Despite the intriguing positive LOD score obtained with GRL, linkage to bipolar disorder could not be demonstrated in the region examined. PMID- 7986887 TI - A comparison of plasma homovanillic acid in the deficit and nondeficit subtypes of schizophrenia. AB - Plasma homovanillic acid (pHVA) was measured over a 13 hr-period in 16 DMS-III-R schizophrenic patients, all treated with neuroleptic drugs and in a stable clinical and therapeutic status for the preceeding 12 months. Patients were categorized into deficit (n = 9) and nondeficit (n = 7) forms of schizophrenia according to the Schedule for the Deficit Syndrome (SDS) criteria. As compared to the nondeficit group, deficit patients display significantly lower mean pHVA concentrations from 9 AM to 12 AM and a lack of diurnal variations. None of the demographic, clinical, and therapeutic variables can explain these biological differences. These data suggest a specific biochemical basis for the deficit syndrome of schizophrenia as defined by the SDS criteria, that is, primary, enduring, negative symptoms. PMID- 7986888 TI - Noradrenergic and adrenergic functioning in autism. AB - A neurochemical assessment of noradrenergic and adrenergic functioning was carried out with autistic patients and normal control individuals. Norepinephrine and related compounds were measured in autistic (n = 17 unmedicated, 23 medicated; age range 9-29 years old) and normal controls (n = 27; age range 9-36 years old). Plasma levels and urinary excretion of 3-methoxy-4-hydroxy phenylglycol (MHPG) were measured, as were urinary excretion rates of norepinephrine (NE), epinephrine (EPI), and vanillylmandelic acid (VMA). No significant group mean differences were seen between the autistic and control groups. In both the autistic and control groups urinary excretion rates of norepinephrine and epinephrine were substantially higher in the afternoon-evening (5-11 PM) compared to the overnight (11 PM-7 AM) collection period. Based on our neurochemical assessment, marked abnormalities in basal noradrenergic functioning do not appear to be present in autism. PMID- 7986889 TI - Effects of cocaine on sensory inhibition in rats: preliminary data. AB - The purpose of this study was to determine the effect of cocaine on inhibitory sensory processing mechanisms in the brain. To accomplish this aim, recording electrodes were surgically placed into the vertex region of 12 rats. After recovery from surgery, rats were injected once daily for 5 days with either cocaine (20 mg/kg, IP) or saline. Immediately and 23 hr after each injection, the rats were tested for sensory gating mechanisms. They were presented with a series of two clicking sounds, a conditioning and testing click, delivered 0.5 sec apart, and the amplitude of the N40 responses to each of these clicks was recorded. The ratios of the amplitude of the N40 response to the testing click over that of the conditioning click (T/C ratio) were calculated for each animal for each testing period. The T/C ratios of the control (Saline-injected) animals were less than one, indicating that the conditioning stimulus was able to activate inhibitory neural pathways, producing a decrease in the response to the testing stimulus. The T/C ratios of the cocaine-treated animals were significantly greater than those of controls when the tests were conducted either immediately after injection or 23 hr later. These observations suggest that cocaine can impair mechanisms involved in the gating of responses to auditory stimuli. The higher T/C ratio found at 23 hr after cocaine injection suggests that an impairment in the gating mechanism may be produced by an arousal response that is associated with the environment in which the animals had been injected with cocaine. PMID- 7986890 TI - A review of GHRH stimulation test in psychiatry. AB - We critically reviewed controlled investigations of the growth hormone releasing hormone (GHRH) stimulation test in depression, anorexia nervosa, bulimia, panic disorder, schizophrenia, and Alzheimer's disease. Comparisons of GH responsiveness between patients and controls within each diagnostic category were equivocal and in some cases contradictory. Factors that may contribute substantially to the inconsistent findings within diagnostic categories include (1) the variability of GHRH-simulated GH among control groups; (2) the lack of uniformity in test procedures and outcome measures; and (3) the age and gender of subjects. In addition, the individual reproducibility of the GHRH stimulation test has not been adequately investigated and until the test's stability within subjects can be determined, the validity of interpretations resulting from the GHRH simulation test are in question. PMID- 7986892 TI - Comparison of cyproterone acetate (CPA) and leuprolide acetate (LHRH agonist) in a chronic pedophile: a clinical case study. PMID- 7986891 TI - Amineptine dependence and schizophrenia. PMID- 7986893 TI - Changes in the dopaminergic innervation of monkey prefrontal cortex during late postnatal development: a tyrosine hydroxylase immunohistochemical study. PMID- 7986894 TI - Coagulase-negative staphylococci: pathogens associated with medical progress. AB - Coagulase-negative staphylococcal bacteremia and infections of prosthetic medical devices have become major clinical problems. Efforts to differentiate contaminating from infecting isolates consume the time of microbiology laboratory personnel; decisions over when and with what to institute therapy for multiresistant isolates consume the energy of clinicians; and the need to institute expensive parenteral antimicrobial therapy consumes the hospital pharmacy budget. It is clear that the increased incidence of coagulase-negative staphylococcal infections is the result of medical progress and is due to the use of invasive and indwelling medical devices. Multiresistant organisms have evolved that will survive in the presence of antimicrobial agents designed to eradicate more traditional pathogens. They have an ecological niche on human skin from which they are difficult to eradicate, and they have adapted themselves to survive on inert devices designed to persist indefinitely in the human body. Since it is likely that the use of prosthetic medical devices will continue to increase, we need to device innovative strategies for the diagnosis, treatment, and prevention of infections of these indwelling foreign bodies. Studies that will address these issues should be a major goal of future research on hospital acquired infections. PMID- 7986895 TI - Bloodstream infections at a Norwegian university hospital, 1974-1979 and 1988 1989: changing etiology, clinical features, and outcome. AB - All episodes of bloodstream infection in patients admitted to a Norwegian university hospital in 1974-1979 and in 1988-1989 were analyzed; altogether, there were 1,447 episodes involving 1,286 patients, and 54.3% of all episodes were hospital-acquired. The incidence of bloodstream infection increased between the two periods studied from 4.26/1,000 admissions to 8.71/1,000. Crude mortality rates were 27.6% and 18.8% and attributable mortality rates were 12.3% and 6.9% in the first and second periods, respectively. Patients > 60 years of age accounted for more than half of the bloodstream infections; mortality in this group was significantly higher than that among younger patients (31.4% vs. 13.9%). The frequency of isolation of Enterobacteriaceae decreased from 48% in the first period to 34% in the second, while the rate of isolation of coagulase negative staphylococci increased from 6.5% to 16.9%. The shift in etiology may be explained in part by the occurrence of significantly more bloodstream infections related to intravascular devices, endocarditis, and skin and wound infections and of significantly fewer episodes related to abdominal or genitourinary disease in the second than in the first period. Almost all isolates of Enterobacteriaceae were susceptible to newer cephalosporins and aminoglycosides. In 1974-1979, 96 (69.1%) of 139 patients with septic shock died; in 1988-1989, the figure was 35 (52.2%) of 67 patients (P = .019). Clinical factors predictive of an adverse outcome were septic shock (odds ratio for first/second period, 12.7/4.6), intensive care treatment (not significant/10.6), malignant disease (4.6/2.6), any underlying disease (4.2/not significant), diabetes mellitus (3.6/not significant), age of > 60 years (not significant/3.0), and pulmonary source of infection (not significant/2.8). PMID- 7986896 TI - Photo quiz. Orf. PMID- 7986897 TI - Brain abscess due to Gordona terrae in an immunocompromised child: case report and review of infections caused by G. terrae. AB - A brain abscess complicated antineoplastic chemotherapy for a primary cerebral rhabdoid tumor in an immunocompromised boy. Culture of purulent exudate obtained by surgical puncture of an intracranial hematoma yielded a gram-positive microorganism initially identified as a Rhodococcus species by conventional biochemical analysis; however, the isolate was subsequently identified as Gordona terrae by ribosomal DNA analysis. To our knowledge, this is the third case of human infection caused by G. terrae and the first case of a brain abscess due to this organism. As this case demonstrates, this species may cause opportunistic invasive infection in severely immunocompromised patients. The identity of clinical isolates believed to be G. terrae should be confirmed by molecular methods until better species-specific phenotypic markers become available. PMID- 7986898 TI - Infections due to nontuberculous mycobacteria in kidney, heart, and liver transplant recipients. AB - Infections due to nontuberculous mycobacteria (NTM) in solid-organ transplant recipients are infrequent but may be a major cause of morbidity. We describe four cases of NTM infection in solid-organ transplant recipients. The manifestations included a nodule secondary to Mycobacterium kansasii infection in a heart transplant recipient, a cutaneous lesion and a pulmonary nodule secondary to M. kansasii infection in a renal transplant recipient, tenosynovitis secondary to Mycobacterium chelonae infection in a renal transplant recipient, and cutaneous lesions secondary to M. chelonae infection in a liver transplant recipient. We also summarize previously reported cases of NTM infections in solid-organ transplant recipients; common manifestations of NTM infections in solid-organ transplant recipients include cutaneous lesions of the extremities, tenosynovitis, and joint infection. Histopathologic examination of aspirates or biopsy specimens from involved areas and staining and culture for mycobacteria are essential for diagnosis. Treatment of NTM infection most commonly involves surgery, reduction in doses of immunosuppressive medications, and/or therapy with antimycobacterial medications; these treatments are often associated with a good outcome. PMID- 7986899 TI - Effects of recent sexual activity and use of a diaphragm on the vaginal microflora. AB - We prospectively studied 40 women over a median period of 28 weeks to ascertain the effects on vaginal microflora of sexual intercourse alone compared with sexual intercourse associated with use of a diaphragm with a spermicide (diaphragm/spermicide). Compared with no sexual intercourse, sexual intercourse with use of a diaphragm/spermicide in the preceding 3 days was strongly associated with increases in rates of vaginal colonization with uropathogenic flora, including Escherichia coli (P < .0001), other gram-negative uropathogens (P = .0045), group D streptococci (P = .014), and group B streptococci (P = .0015). Except for E. coli colonization, no such increases in rates of vaginal colonization were seen at visits preceded by sexual intercourse without use of a diaphragm/spermicide. Compared with no sexual intercourse, sexual intercourse with use of a diaphragm/spermicide in the preceding 3 days also was associated with a marked increase in rates of candidal colonization (P < .0001) and with a decrease in rates of lactobacillus colonization (P < .0001). We conclude that bacterial and fungal microflora in the vagina are strongly influenced by recent use of a diaphragm/spermicide and minimally affected by sexual intercourse alone. PMID- 7986900 TI - Role of antibiotics in the treatment and prevention of acute and recurrent cholangitis. AB - Cholangitis is usually the consequence of a combination of factors: impairment of the flow of bile and bacterial colonization of the biliary tract. Although reestablishing biliary drainage is the mainstay of treatment, antibiotics play an important role in the management of cholangitis. In this review, the use of antibiotics for treatment, prophylaxis, and maintenance therapy is discussed. Antibiotics for the treatment of acute cholangitis should be given for 7-10 days in therapeutic dosages and may allow a more selective timing of further interventions. Antibiotic prophylaxis for cholangitis ought to be given as a single (high) dose shortly before surgical or nonsurgical manipulations of the biliary system. Patients with a compromised biliary system (e.g., on account of an endoprosthesis in situ or hepaticojejunostomy) who are prone to develop recurrent bouts of cholangitis may benefit from antibiotic maintenance therapy, given daily in lower-than-therapeutic dosages. PMID- 7986901 TI - Strategies for the prevention of cytomegalovirus disease after marrow transplantation. AB - The purposes of this review are to examine the epidemiology of disease due to cytomegalovirus (CMV) in recipients of autologous and allogeneic marrow transplants and to compare different antiviral regimens used for the prevention of such disease in recipients of allogeneic marrow transplants, with an emphasis on ganciclovir. In seven studies, ganciclovir reduced the incidence of CMV infection and disease after allogeneic marrow transplantation. In one study mortality after transplantation was reduced because of a decreased rate of CMV related death among ganciclovir-treated patients. Ganciclovir was effective when given to all CMV-seropositive patients (prophylaxis) or to patients who were considered at high risk for CMV disease on the basis of a positive surveillance culture (early treatment). The effectiveness of ganciclovir for the prevention of CMV infection and disease is limited by drug-induced neutropenia. Experience with other antiviral agents, such as foscarnet, has been limited. Initial studies of the adoptive transfer of CMV-specific CD8+ cytotoxic T cells have been conducted. In short, ganciclovir is currently effective for the prevention of CMV disease in allogeneic marrow transplant recipients, but its usefulness is limited by neutropenia. Future studies must be aimed at confining the toxicity of ganciclovir to patients at the highest risk for CMV disease. PMID- 7986902 TI - Environmental control of tuberculosis: continuing controversy. AB - The incidence of tuberculosis--and, more important, that of multidrug-resistant tuberculosis--have risen drastically in the past decade. Nosocomial outbreaks have alerted health-care workers to the hazards of the spread of tuberculosis. The use of environmental control modalities (e.g., ventilation, air filtration, and ultraviolet irradiation) and personal protective devices has been explored in the medical, legislative, and public forums. New regulations and legislation have created controversy over the recommendations and their interpretation. In this review we present the theory behind the rational selection of environmental control modalities and personal protective devices. We also offer suggestions about the application of specific control techniques and the revision of existing facilities to comply with new standards. PMID- 7986903 TI - Guidelines for preventing the transmission of tuberculosis: a better solution? AB - The incidences of tuberculosis in general and of drug-resistant tuberculosis in particular have increased significantly since 1985 in the United States. The proposed revision of the 1990 guidelines for preventing the transmission of tuberculosis by the Centers for Disease Control and Prevention will be tremendously expensive. A better solution might consist of the implementation of a graded-response strategy depending on the magnitude of the problem posed by tuberculosis in a particular area, reeducation in and strict adherence to the basic principles of infection control, and the investigation of various masks and respirators to determine which are cost-effective. PMID- 7986904 TI - Gastroenteritis due to adenovirus type 41 in an adult with chronic lymphocytic leukemia. AB - We describe a case of gastroenteritis due to adenovirus type 41 that lasted for 46 days (until the patient's death) in a 56-year-old woman with terminal B cell chronic lymphocytic leukemia. Adenovirus particles were detected by electron microscopy in five stool specimens collected between 5 and 39 days after the onset of the diarrheal illness. The virus was identified as adenovirus type 41 by viral neutralization tests and other assays. We discuss the potential pathogenicity of subgenus F adenoviruses in immunocompromised patients. PMID- 7986905 TI - Successful treatment of sinusitis caused by Cunninghamella bertholletiae. AB - Seventeen cases of infections due to Cunninghamella species have been reported worldwide in humans, and there have been only three survivors. We report a case of paranasal sinusitis due to Cunninghamella bertholletiae in an elderly patient who had diabetes mellitus and myelodysplasia. After receiving 7 weeks of therapy with deoxycholate amphotericin B (44 mg/kg or a total of 3 g) and rifampin, the patient was cured and did not have to undergo radical surgery. PMID- 7986906 TI - Haemophilus aphrophilus as a rare cause of arthritis. AB - A case of septic arthritis due to Haemophilus aphrophilus is presented. This organism has rarely been reported as a cause of bone or joint infections. We believe this is the third reported case of septic arthritis caused by this microorganism. We review the clinical and bacteriologic findings and the previously reported cases of infection caused by H. aphrophilus. Treatment with ceftriaxone was followed by full recovery without sequelae. PMID- 7986907 TI - Pediatric osteomyelitis in Panama. AB - Two hundred forty-one children who had osteomyelitis during a 19-year period, 1974 through 1992, were identified by chart review. Acute osteomyelitis or chronic osteomyelitis was the diagnosis for 221 (92%) and 20 (8%) of the children, respectively. Bacteriologic etiology was documented in 137 (57%) of the cases. Staphylococcus aureus, Pseudomonas aeruginosa, Salmonella species organisms, and Haemophilus influenzae type b were isolated from 97 (40%), 10 (4%), 8 (3%), and 7 (3%) of the children, respectively. S. aureus was the predominant microorganism in all age groups, whereas H. influenzae occurred only in children younger than 2 years of age. P. aeruginosa was recovered predominantly from children with a penetrating injury of the foot, while salmonella bone infections were diagnosed in patients with sickle cell disease. These data provide guidelines for the initial work-up for and management of osteomyelitis in children living in developing Latin American countries. PMID- 7986908 TI - Meningitis due to Xanthomonas maltophilia: case report and review. AB - Xanthomonas maltophilia is being increasingly recognized as an opportunistic pathogen in debilitated patients. We report a case of postoperative meningitis due to X. maltophilia and review the cases of X. maltophilia meningitis reported in the literature. Because X. maltophilia is often resistant to multiple beta lactam agents, including cephalosporins and imipenem, trimethoprim sulfamethoxazole appears to be the drug of choice for treatment of X. maltophilia meningitis. PMID- 7986909 TI - Preliminary report on an automated screening test for detection of antibody to human immunodeficiency virus type 1 in whole blood. AB - We developed and evaluated an automated screening test for antibody to human immunodeficiency virus type 1 (HIV-1) using EDTA-2Na-treated whole blood and an extract of paper disk-absorbed dried whole blood from 60 hemophiliacs infected with HIV-1 and 210 diseased and healthy controls. The specificity and the sensitivity of this system were judged to be 100% with both the whole blood and the extract. This test allows measurement of HIV-1 antibody in whole blood and dried whole blood on a small paper disk and gives a result within 13 minutes; the system can process 150 samples per hour. Therefore, it may be useful at many testing sites, such as emergency departments, intensive care units, blood banks, and commercial laboratories, as well as for mail-order testing from remote areas and developing countries. PMID- 7986911 TI - Use of albendazole for disseminated microsporidian infection in a patient with AIDS. AB - Disseminated microsporidian infection in patients with AIDS has been recently reported and is associated with the genus Encephalitozoon and the newly described genus Septata. We report a case of symptomatic, disseminated intestinal, urinary, nasal, and ocular microsporidian infection in a patient with AIDS. A dramatic response to therapy with albendazole was observed. PMID- 7986910 TI - Successful treatment of extensive posttraumatic soft-tissue and renal infections due to Apophysomyces elegans. AB - We describe the clinical course and successful treatment of a previously healthy man who, after experiencing trauma, presented with severe cutaneous mucormycosis due to Apophysomyces elegans and subsequently developed secondary renal infection. A multidisciplinary approach employing aggressive surgical debridement and therapy with hyperbaric oxygen, liposomal amphotericin B, and interferon gamma was successful in controlling his infection, obviating the need for nephrectomy. PMID- 7986912 TI - Alcoholism and rapid progression to AIDS after seroconversion. AB - Rapid progression of infection with human immunodeficiency virus type 1 (HIV-1) to AIDS after seroconversion is rare; it has been associated with coinfection by cytomegalovirus or human T lymphotrophic virus type I. We describe an alcoholic patient whose condition progressed to AIDS 3 months after HIV-1 seroconversion occurred. Culture of peripheral blood mononuclear cells yielded a syncytium inducing variant of HIV-1. T lymphocytes showed no spontaneous cytotoxic activity against HIV-infected cells, nor could such activity be demonstrated following stimulation with HIV-1 antigen in the presence of recombinant interleukin-2. We hypothesize that our patient's accelerated course was due to alcohol abuse, which may have suppressed T cell function and stimulated HIV replication. PMID- 7986913 TI - Successful treatment of systemic and local infections due to Exophiala species. AB - We report the successful treatment of three cases of infection due to Exophiala species. These organisms belong to the heterogeneous group of dematiaceous (darkly pigmented) fungi. Two cases of infection occurred in organ transplant recipients who were receiving immunosuppressive medications. Both of these infections remained localized to the subcutaneous tissues and were successfully treated with surgical excision of the lesions. We also describe what is to our knowledge the first reported case of prosthetic valve endocarditis due to Exophiala castellanii that was managed with a combination of medical and surgical therapies. Exophiala species remain an uncommon cause of infection. However, as the population of immunocompromised patients continues to grow and further improvements in the microbiological techniques for identification of these fungi occur, these organisms will be recognized with increasing frequency as a cause of human disease. PMID- 7986914 TI - Detection of Septata intestinalis in stool specimens and coprodiagnostic monitoring of successful treatment with albendazole. AB - We describe two patients with AIDS and chronic diarrhea in whom the microsporidian Septata intestinalis was detected with use of light and electron microscopic coprodiagnostic techniques. The ultrastructure of the microsporidian spores found in their stool specimens was distinctly different from that of Enterocytozoon bieneusi, another intestinal microsporidian found in patients infected with human immunodeficiency virus. Electron microscopic examination of duodenal biopsy specimens available from one of the patients enabled identification of S. intestinalis and confirmed the similarity of spores found in feces and in duodenal tissue. Both patients' diarrhea stopped when they were treated with albendazole. Coprodiagnostic monitoring indicated disappearance of the parasites and allowed the diagnosis of a relapse in one patient, who responded well to a second course of treatment. PMID- 7986916 TI - Delayed-onset postpartum meningitis due to group B streptococcus. PMID- 7986915 TI - Amebic abscess of the spleen complicated by metronidazole-induced neurotoxicity: case report. AB - We describe a patient with a liver abscess due to Entamoeba histolytica, in whom metronidazole therapy (total dose, 21 g over 14 days) was complicated by reversible deafness, tinnitus, and ataxia and who relapsed 5 months later with a splenic abscess. Two courses of tinidazole (the second in combination with percutaneous aspiration of the abscess) were required to achieve cure. PMID- 7986917 TI - Severe myopathy in an injection drug user coinfected with human immunodeficiency virus type 1 and human T cell leukemia virus type II. PMID- 7986918 TI - Evidence implicating rifampin-independent antiplatelet antibodies in the pathogenesis of rifampin-induced immune thrombocytopenia. PMID- 7986919 TI - The changing spectrum of fever of unknown origin in Mexico. PMID- 7986920 TI - Reduction in serum concentrations of ciprofloxacin after administration of ursodiol to a patient with hepatobiliary disease. PMID- 7986921 TI - Iatrogenic streptococcal meningitis. PMID- 7986922 TI - A French case of laboratory-acquired disseminated Penicillium marneffei infection in a patient with AIDS. PMID- 7986923 TI - Toxic epidermal necrolysis in a patient with AIDS. PMID- 7986924 TI - Are rifampin-resistant Streptococcus pneumoniae strains a consequence of the increase in cases of tuberculosis? PMID- 7986925 TI - Tumors of the colon increase the risk of developing Streptococcus bovis endocarditis: case-control study. PMID- 7986926 TI - Visceral leishmaniasis following treatment with liposomal amphotericin B. PMID- 7986927 TI - Hepatitis D virus infection in drug addicts infected with the human immunodeficiency virus. PMID- 7986928 TI - Group B streptococcal bacteremia associated with adenocarcinoma of the stomach. PMID- 7986929 TI - Cytomegalovirus polyradiculopathy caused by a ganciclovir-resistant strain. PMID- 7986930 TI - Effectiveness of amphotericin B in lipid emulsion for treating fungal septicemia in granulocytopenic patients. PMID- 7986931 TI - Bacteremia in a patient with non-urinary-tract infection due to Corynebacterium urealyticum. PMID- 7986932 TI - Infectious Diseases Society of America and health care reform. PMID- 7986933 TI - Proposed health care reform amendments to guarantee patients with chronic illness access to medically necessary specialty care. PMID- 7986934 TI - Proceedings of the 4th International Conference Biointeractions '93. Molecular aspects of biomaterials. 29 August-1 September 1993, Noordwijkerhout, The Netherlands. PMID- 7986935 TI - Surface modification of polymers for medical applications. AB - Most of the conventional materials do not meet the demands required for both their surface and bulk properties when used as biomaterials. An effective approach for developing a clinically applicable biomaterial is to modify the surface of the material which already has excellent biofunctionality and bulk properties. This review article focuses on the surface modification of polymers by grafting techniques, which have long been known in polymer chemistry but are not yet widely applied to biomaterials. A grafted surface can be produced primarily either by graft polymerization of monomers or covalent coupling reaction of existing polymer molecules onto the substrate polymer surface. The major surface properties that should be modified include two kinds of biocompatibility. One is the surface property that elicits the least foreign-body reactions and the other is the cell- and tissue-bonding capability. In addition, physiologically active surfaces with, for instance, selective adsorbability may be required. Attempts to produce these biocompatible or biospecific surfaces by grafting techniques are briefly overviewed in this article. PMID- 7986936 TI - Biomaterials for blood-contacting applications. AB - Consideration of biomaterials for blood-contacting applications should take into account blood-biomaterial interactions, factors influencing the blood response and evaluation procedures. Examination of blood-biomaterial interactions indicates that relevant features are protein adsorption, platelet reactions, intrinsic coagulation, fibrinolytic activity, erythrocytes, leucocytes and complement activation. Factors influencing the blood response to a biomaterial in clinical application are the biomaterial structure, the presence of an antithrombotic agent, the patient status as determined by the disease and drug therapy, and the nature of the application. Evaluation options for biomaterials are clinical, in vivo, ex vivo and in vitro, with ex vivo and in vitro procedures relevant for biomaterial development. PMID- 7986937 TI - Xenografts for tendon and ligament repair. AB - Collagenous materials, usually of bovine or equine origin, have been popular starting points for the development of xenograft prostheses for tendon and ligament repair. Xenografts are highly attractive as they carry small risk of infectious disease, do not compromise the patient's remaining tissues and may have the 'correct' structure as the component being replaced. Animal studies, on dog, rabbit and chicken, have shown tremendous potential for this use of xenograft material as a tendon replacement. Why, therefore, have xenografts been almost universally a total failure in clinical application? The reasons would appear to be two-fold: the animal models have not been appropriate to the intended clinical use and the cross-linking of xenograft materials has not been optimized. Our work on xenograft, heterograft and autograft tissues indicates that both aspects deserve more attention. Quantitative histology indicates that the extent and type of response to xenograft materials differs widely with degree of cross-linking (glutaraldehyde). Attention must also be given to the join of the graft to the host. For both tendon and ligament the join is a site of particular fragility. Even with adequate strength in the mid-substance, tendon and ligament grafts can, and do, fail at the join. We have investigated a variety of mechanisms for joining tendon to tendon and ligaments to bone. The failures of these methods present some insight into the biology of the repair process involved and into how failure may be avoided in future. PMID- 7986938 TI - Biocompatibility of silver-coated polyurethane catheters and silver-coated Dacron material. AB - The local effects of silver-coated polyurethane catheters and Dacron material were compared to uncoated polyurethane catheters and Dacron material in a long term implantation test using rabbits. The tissue-implant interaction was analysed by investigating the type and number of inflammatory cells, capillaries, fat tissue, the extent of fibrosis, thickness of the fibrous capsule, number and distribution of silver particles, and the size of giant cells. Silver-coated and uncoated materials displayed comparable signs of inflammation and tissue reaction. PMID- 7986939 TI - Application of new coatings for vascular grafts based on polyacrylic systems with antiaggregating activity. AB - A study has been made of the behaviour of knitted and woven Dacron mesh used in the preparation of vascular grafts when coated with either a layer of poly(2 hydroxyethyl methacrylate) or co-polymers of 2-hydroxyethyl methacrylate with 5, 10 or 20 wt% of an acrylic derivative of salicylic acid, 2-methacryloyloxybenzoic acid. In vitro studies were carried out to quantify the loss of polymer under flow conditions, and ex vivo studies were done in dogs to quantify the deposition of 111In-oxine-labelled platelets. The treated materials showed a lesser deposition of platelet thrombi when compared with the control group. PMID- 7986940 TI - New material for low-cost intraocular lenses. AB - A UV-hardening lacquer material based on polyurethane, used in Philips compact disc lens systems, was tested as suitable material for low-cost intraocular lenses (IOLs). A slightly changed composition (code number I-0.5A) came out as the best and was subsequently tested, with reference to poly(methyl methacrylate) (PMMA), as a 'lobster-claw' lens in Hollander rabbit eyes for a period of 24 wk. No carcinogenic effects were found, while only minor vascularization of the cornea at the incision area occurred. The in vitro biocompatibility tests of the material were positive. Scanning electron microscopy images of the IOLs at 2, 6, 12 and 24 wk postoperative showed portions of an acellular membrane, multinuclear giant cells which hyalinize and stay as pigmented plaques, microphages and fibroblasts with fibrillar strands, long pseudopodia, and broad microplicea. The chosen UV lacquer showed a foreign body reaction and properties comparable with PMMA, and is suitable for manufacturing low-cost IOLs. PMID- 7986941 TI - Design of nasoseptal cartilage replacements synthesized from biodegradable polymers and chondrocytes. AB - Reconstructive and aesthetic surgery of the nose is a challenging problem in facial plastic surgery. In this study, biodegradable polymers composed of polyglycolic acid (PGA) and poly-L-lactic acid (PLLA) and their co-polymers were used to produce templates to transplant cells and promote regeneration of structural cartilage. A highly porous anatomically shaped three-dimensional non woven PGA fibre network was sprayed with a coating polymer solution. Reinforcement of the outer circumference of the 12 nasoseptal constructs using high molecular weight PLLA further stabilized the constructs during the process of neomorphogenesis of cartilage, both during in vitro incubation and in vivo implantation. These cell transplantation devices also proved to be adhesive substrates for dissociated bovine chondrocytes. When implanted subcutaneously into nude mice, the polymer templates guided the reorganization after 8 wk of the bovine chondrocytes into neocartilage in the precisely designed size and shape of the original size and shape of the polymer delivery device. All implants loaded with chondrocytes showed evidence of formation of histologically organized hyaline cartilage. The implantation of nasal scaffolds without cells did not show cartilage formation. The technique of tissue engineered growth of cartilage has potential applications in orthopaedic, plastic and reconstructive, and craniomaxillofacial surgery. PMID- 7986942 TI - Molecular biointeractions of biomedical polymers with extracellular exudate and inflammatory cells and their effects on the biocompatibility, in vivo. AB - The stability of biomedical polymers in physiological environments is crucial for the normal operation of devices, as well as determining their effect on the tissue response. Degradation is an important factor in polymer biocompatibility, since the environment of the human body can be aggressive to polymers. Most implanted polymers suffer degradation to some extent, and the kinetics and mechanisms of the processes can be affected significantly by various biologically active species, especially enzymes, lipids, peroxides, free radicals and phagocytic cells. The degradation of poly(caprolactone) and poly(DL-lactic acid) under controlled in vivo conditions was studied using a poly(methyl methacrylate) chamber designed to control the exposure of polymers to physiological environments. In particular they may be designed to allow access of extracellular exudate only or access to cells as well as the fluid. The chambers, sealed with filters of pore size either 0.45 micron (impervious to cells) or 3.0 microns (allowing cells to enter the chamber), were implanted subcutaneously into experimental animals for 10, 20 and 30 wk periods. Degradation and molecular interactions of the polymers were characterized by gel permeation chromatography and scanning electron microscopy. The extracellular exudate formed within the implanted chamber is active in promoting the degradation of some biomedical polymers. Inflammatory cells are involved in the biodegradation of implanted polymers by releasing biologically active species such as free radicals into the area surrounding the implant. The data have demonstrated that the hydroxyl radical is likely to be one of the main causes of polymer degradation. PMID- 7986943 TI - Differential surface binding of albumin, immunoglobulin G and fibrinogen. AB - Protein-protein interactions, as well as the nature of the surface, significantly affect the activity of a specific protein towards a defined surface. Indications are that protein-protein associations may affect antibody detectability, but in some cases this is the result of altered antigenic accessibility rather than physical removal of the molecule. The antibody binding patterns are also quite variable over an entire methyl-silanol wettability gradient on silicon, suggesting that the surface itself is affecting protein-protein and protein protein-surface associations. Ellipsometric studies were carried out on the gradients which were incubated in single; binary and tertiary physiological concentration solutions of human albumin, immunoglobulin G (IgG) and fibrinogen. The ellipsometric-antibody detectability of the proteins on such surfaces were found to be variable, depending upon the location on the gradient and the order and combination in which the proteins were presented to the surface. Radiolabelled proteins were studied on discrete regions of these gradients. Competitive effects of albumin were found to be inhibitory (negative) with respect to IgG adsorption on hydrophobic surfaces, while enhancing IgG deposition on hydrophilic surfaces (positive). Scanning force microscopy in the so-called tapping mode indicates that proteins, particularly IgG, organize themselves differently with respect to surfaces, depending upon the nature of the surface and the presence of other proteins. PMID- 7986944 TI - Transient changes in the mononuclear phagocyte system following administration of the blood substitute liposome-encapsulated haemoglobin. AB - We have examined the effects of administration of the blood substitute, liposome encapsulated haemoglobin (LEH), in the normovolaemic rat. Test groups included LEH, lyophilized EH, the liposome vehicle, unencapsulated haemoglobin and normal saline, which were injected into the tail vein (n = 6; n = 3 for sham and saline groups). Administration of LEH (2.5 g phospholipid, 1.25 g haemoglobin/kg rat) was followed by blood sampling at 2 h, 24 h, 1 wk and 2 wk. Blood samples were analysed for alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, gamma-glutamyltransferase, total and indirect bilirubin, serum creatinine, albumin, total protein, lipase, cholesterol, blood urea nitrogen, haematocrit, haemoglobin and differential white blood cell counts. Observed effects following injection were mild and transient, with baseline values recovered at 1 wk. Alanine aminotransferase increased moderately in the LEH group at 24 h to 601 +/- 143 IU/dl (P < 0.0001), with a return to baseline at 1 wk. Aspartate aminotransferase showed a smaller increase from 46 +/- 5 to 162 +/- 40 at 24 h and also returned to baseline at the 1 wk measurement (P < 0.001). The transient increase in serum transaminases was not observed for the lyophilized LEH group. Tissue sections showed accumulation of liposome groups in resident macrophages of the liver and spleen. Incubation of an adherent population of human peripheral blood monocytes with LEH in culture did not elicit the production of the inflammatory cytokine, tumour necrosis factor. Pre-incubation of monocytes with LEH prior to exposure to endotoxin did, however, result in a reduced expression of this inflammatory cytokine. PMID- 7986945 TI - Adhesion of coagulase-negative staphylococci and adsorption of plasma proteins to heparinized polymer surfaces. AB - Protease treatment of cells of coagulase-negative staphylococci reduced the adhesion of bacteria to heparinized polyethylene preadsorbed with serum. Fibronectin (Fn), fibrinogen (Fg), vitronectin, complement factor C3c, plasminogen, laminin and to a low extent albumin were detected on tridodecylmethylammonium chloride (TDMAC)-heparinized polyvinyl chloride (PVC) catheters extirpated from the circulation of patients. Using a perfusion model we show that during the first hours of perfusion with human plasma, Fn and Vn dominate, whereas after 22 h of perfusion Fg is the dominant protein. Field emission scanning electron microscopy and atomic force microscopy studies on TDMAC-heparinized catheters as well as on end-point attached heparinized PVC catheters indicate that quantitatively more Fg than Fn is exposed on these surfaces after prolonged exposure (> 22 h) to human plasma. PMID- 7986946 TI - Inhibition of the calcification of porcine valve tissue by selective lipid removal. AB - Since the development of cardiac prostheses, numerous chemical treatments have been assayed to prevent the process of their mineralization, causing 60% of the failures. The effect of the extraction of lipids from the tissue employed in porcine valves is assessed in a model of subcutaneous implantation in rats. Tissue from aortic and pulmonary porcine valves was treated with chloroform methanol and 0.625% glutaraldehyde and was implanted into young rats for periods of 21 and 60 d. The calcium accumulated was then quantified by atomic absorption. The effectiveness of this treatment is demonstrated by the detection of much lower calcium values than in the control group. For aortic valve tissue, the values obtained were 40.5 and 188.1 micrograms Ca2+/mg dry weight of tissue for implantation times of 21 and 60 d, respectively, versus 5.48 and 1.4 micrograms Ca2+/mg dry weight of tissue for the same tissue treated with chloroform methanol. The values obtained with pulmonary valve tissue were very similar: 72.46 and 108.06 micrograms Ca2+/mg dry weight tissue versus 0.67 and 0.80 micrograms Ca2+/mg dry weight tissue for implantation periods of 21 and 60 d, respectively. Thus, phospholipids may be totally or partially responsible for the calcification of the porcine valve tissue employed in the construction of cardiac bioprostheses. PMID- 7986947 TI - Use of microelectrodes as electrochemical sensors of metal ions released from biomaterials. AB - In vitro studies to determine Fe3+ levels in mice liver samples were performed using platinum microelectrodes and atomic absorption spectrophotometry. Microelectrodes have been shown to be useful for quantitative analysis of metal ions released during the biodegradation process that occurs on implanted metallic biomaterials. PMID- 7986948 TI - Titanium with different oxides: in vitro studies of protein adsorption and contact activation. AB - Adsorption of albumin (HSA) and fibrinogen (Fib) from human blood plasma onto titanium surfaces with varying oxide properties was studied with an enzyme-linked immunosorbent assay. The intrinsic activation of blood coagulation (contact activation) was studied in vitro using a kallikrein-sensitive substrate. The sample surfaces were characterized with Fourier transform Raman spectroscopy. Auger electron spectroscopy and atomic force microscopy. Low Fib and high HSA adsorption was observed for all titanium samples except for the radio frequency plasma-treated and water-incubated samples, which adsorbed significantly lower amounts of both. Oxide thickness and carbon contamination showed no influence on protein adsorption or contact activation. Smooth samples with a surface roughness (Rrms) < 1 nm showed some correlation between surface wettability and adsorption of Fib and HSA, whereas rough surfaces (Rrms > 5 nm) did not. To varying degrees, all titanium surfaces indicated activation of the intrinsic pathway of coagulation as determined by their kallikrein formation in plasma. PMID- 7986949 TI - Formation of a bone apatite-like layer on the surface of porous hydroxyapatite ceramics. AB - Phosphoric acid solution was used to react with commercial hydroxyapatite (HA) powders to demonstrate the possibility of converting HA to non-stoichiometric apatite and thus to treat porous HA ceramics, to form a thin bone-apatite like layer on the HA ceramic surface. Such a carbonate-containing non-stoichiometric apatite "bioceramic" would be more efficient in bone bonding or bone formation, due to its analogy to natural bone apatite. PMID- 7986950 TI - Immobilization of human thrombomodulin onto poly(ether urethane urea) for developing antithrombogenic blood-contacting materials. AB - Thrombomodulin (TM) is a newly described endothelial cell-associated protein that functions as a potent natural anticoagulant by converting thrombin from a procoagulant protease to an anticoagulant. In this study, focussing on the application of TM for biomedical materials, recombinant human TM (hTM) was immobilized onto the polymers for medical use, and the evaluation of their antithrombogenicity and the interaction with platelets were investigated. As the base polymer for immobilization reaction, poly(ether urethane urea) (PEUU), which was reported to have good blood compatibility, was used. hTM-immobilized PEUU showed superior antithrombogenic activity, such as the prolongation of plasma recalcification time and the inhibition of thrombin-induced platelet aggregation, though the amount of immobilized hTM was very small (i.e. less than 1 microgram/cm2). Platelet adhesions onto hTM-immobilized PEUU were not observed. These results show that the immobilization of hTM does not change the native good blood compatibility of PEUU, but provides excellent anticoagulant activity. PMID- 7986952 TI - Antibody response in rats against non-toxic glucose sensor membranes tested in cell culture. AB - Several glucose sensors have been developed, but none are commercially available. The most urgent in vivo problem is the drift of glucose sensor output with time, which may be caused by leakage or denaturation of glucose oxidase, and events at the body-sensor interface such as protein coating, encapsulation with cells, toxicity of the device and inflammation. In the present study, a specific immune response against the outer cellulose acetate membrane of a glucose sensor implanted into rats has also been proved. The immune response against polymeric membranes can be confirmed by detection of specific immunoglobulin G antibodies to cellulose acetate, polyurethane and regenerated cellulose after implantation of the respective membrane. The individually different antibody formation against polymers in rats was amplified by one application of complete Freund's adjuvant in combination with the first implantation. The cell culture results using the fibroblast cell line L-929 showed only a minor toxicity of regenerated cellulose, whereas the other polymers had no effect on cell growth and viability. From the results of this study, it is proposed to integrate immunogenicity as a further parameter for evaluation of the biocompatibility and biosafety of materials or medical devices which are provided for implantation. PMID- 7986951 TI - Recruitment of tissue resident cells to hydrogel composites: in vivo response to implant materials. AB - A model of local cellular recruitment was established using hydrogel matrices composed of alginate implanted subcutaneously into mice. Cells which trafficked to the matrix blocks were recovered and characterized for surface phenotype using fluorescently labelled antibodies and flow cytometry (fluorescence activated cell sorting). Temporal information of the differential recruitment of cells was determined. The basic pattern of recruitment in response to the hydrogels was established and mimicked that seen in a local inflammatory response. Neutrophils (PMN) were rapidly recruited (1 d) followed by macrophages and lymphocytes (1-3 d). Cell surface phenotype studies included the determination of CD3+, CD4+ and CD8+ cells, Mac-1+ cells, and immunoglobulin bearing cells. Microscopic analysis revealed numerous activated PMNs and monocyte derived foamy macrophages. Fluorescence immunocytochemistry of frozen sections of the block revealed that macrophages, CD3+ and natural killer cells were all recruited to the interior of the block. Ultrastructural analysis (transmission electron microscopy) showed highly activated macrophages, with abundant rough endoplasmic reticulum and secretory vesicles. Cells which remained on the surface of the matrix block were CD44 positive migratory cells. Electron microscopic evidence showed foamy macrophages with a varying degree of involvement with the hydrogel material. Surface scanning electron microscopy revealed numerous fibroblast-like cells coating the surface of the block. We suggest that these methods may be used to address the inflammatory response elicited with a a variety of implanted materials such as hydrogels, silicones, ceramics and metals. Furthermore, this model has been useful in determining cellular responses to cytokines and growth factors under similar conditions. PMID- 7986953 TI - Analysis of surface layers on bioactive glasses. AB - FT-Raman spectroscopy proves to be a powerful technique to study surface reactions on bioactive glasses and it eliminates the fluorescence of the organic phase of whole bone, thereby making it possible to compare the reaction layers formed on bioactive glasses with the mineral phase of bone. The spectrum of hydroxycarbonate apatite (HCA) developed on the bioactive glasses is closer to that of bone than synthetic hydroxyapatite (HA) and closely matches that of bone mineral obtained by deproteination of whole human femoral cortical bone. PMID- 7986954 TI - Gap junctional communication and vascular smooth muscle reactivity: use of tetraethylammonium chloride. AB - Oscillatory contractions in uterine smooth muscle are mechanistically related to gap junction complex formation. We have tested the hypothesis that agonist induced oscillations in vascular smooth muscle are also mediated by gap junctions and that gap junctions are important for vascular smooth muscle cell communication. Total RNA from cultured Wistar-Kyoto rat (WKY) mesenteric arterial cells hybridized strongly with a cDNA probe for the message for connexin43, a monomer of the gap junction. In these same cells, the quaternary ion tetraethylammonium (TEA) (10 mM) increased Lucifer yellow dye transfer between contiguous cells, a measure of cell-to-cell communication via gap junctions, approximately 35% above basal levels. Heptanol, an established inhibitor of gap junction communication, completely blocked both basal- and TEA-stimulated dye transfer between neighboring cells. In other experiments, helical strips of superior mesenteric and tail arteries from WKY rats were mounted in tissue baths for measurement of isometric contractile force. TEA (10(-3)-10(-1) M) induced oscillatory contractions (1-5 cycle/min) in both mesenteric and tail arteries. Removal of endothelium did not affect the pattern of TEA-stimulated oscillations. Oscillations to TEA were blocked in a concentration-dependent manner in both arteries by heptanol (10(-7)-10(-3) M). Heptanol (10(-3) M) also significantly reduced (40%) acetylcholine-induced relaxation in the mesenteric artery (contracted with phenylephrine).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7986955 TI - Minor role for direct adrenoceptor-mediated calcium entry in rat mesenteric small arteries. AB - The role of membrane potential-dependent and independent regulation of the intracellular free calcium concentration ([Ca2+]i) was assessed in the mesenteric small arteries of Wistar rats. [Ca2+]i was determined by Fura-2 fluorescence. Membrane potential measurements were made using intracellular microelectrodes. Depolarization with a high-potassium solution (K-PSS) elevated [Ca2+]i and induced contraction. Further addition of 10 microM noradrenaline (NA) did not elevate [Ca2+]i further but enhanced tone. Addition of calcium channel inhibitors (felodipine or D-600) inhibited the maintained rise in [Ca2+]i with K-PSS, but NA still elevated [Ca2+]i and force to about half the previous level. Further addition of either ryanodine or thapsigargin eliminated the rise in [Ca2+]i with NA, although 10-20% of the contraction remained. Simultaneous measurements of membrane potential, [Ca2+]i, and force during cumulative additions of NA or K-PSS in the absence of inhibitors showed similar relations between membrane potential and [Ca2+]i for each means of activation. The results indicate that membrane potential and [Ca2+]i are strongly correlated in mesenteric small arteries. A small part of the [Ca2+]i increase to NA can be attributed to release from intracellular stores. Membrane potential-independent calcium channels that are directly operated by adrenoceptors appear to play a minor role in the regulation of [Ca2+]i in these vessels. PMID- 7986956 TI - Antisense S-oligonucleotide against transforming growth factor-beta 1 inhibits proteoglycan synthesis in arterial wall. AB - Transforming growth factor-beta 1 (TGF-beta 1) is a potent stimulator of proteoglycan (PG) synthesis by cultured smooth muscle cells. To test the hypothesis that TGF-beta 1 stimulates PG synthesis in whole artery wall we have investigated the effect of blocking endogenous TGF-beta 1 using an antisense S oligonucleotide (ASO) directed against the first 7 codons for the N-terminal region of active TGF-beta 1. This sequence reduced TGF-beta 1 secretion by cultured endothelial cells by 40-55%. To determine the effect of the ASO on PG synthesis in whole vessel we chose the rat carotid artery (RCA) maintained in organ culture, a model in which we previously documented endothelial-dependent increases in PG synthesis over time in culture. We report here that the increases in PG in the inner layers of the vessel wall are matched by similar increases in TGF-beta 1 mRNA. To test for the effect of ASO on PG synthesis, small segments of RCA, maintained in organ culture (Medium 199, supplemented with 1% FCS), were exposed on day 6 to either control media, antisense TGF-beta 1, sense TGF-beta 1, or a non-sense sequence at 5, 10 and 20 microM concentrations. Following 24 h exposure to the oligonucleotides, cultures were labelled for a further 24 h with [3H]glucosamine and processed for autoradiography. Antisense TGF-beta 1 at 10 and 20 microM produced a 60% reduction in PG synthesis in the endothelium and adjacent first layer of the media.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7986957 TI - Regulation of the expression of cyclic GMP-dependent protein kinase by cell density in vascular smooth muscle cells. AB - Cyclic GMP-dependent protein kinase (cGMP kinase) is the major receptor protein for cGMP in vascular smooth muscle. Vascular smooth muscle cells (VSMC) isolated from the rat aorta express type I cGMP kinase at high levels, but expression decreases markedly upon passage of the cells. In primary or early passage, the expression of cGMP kinase is lowest when cells are plated at low density as assessed by immunological and Northern analyses. Expression increases at confluence and is maintained in postconfluent cultures. With repeated passaging, however, the levels of cGMP kinase decrease even in confluent and postconfluent cultures so that after several passages enzyme levels are undetectable. The decrease in expression in passaged cells is not due to exposure to serum-derived growth factors, but rather on the repeated exposure of cells to conditions in which cell density is reduced (i.e., subculturing). These results indicate that aortic VSMC grown at low density or those repetitively passaged have reduced expression of cGMP kinase, and thus may not represent appropriate cultures with which to investigate the role of nitric oxide and cGMP in VSMC function. PMID- 7986958 TI - Effects of angiotensin II on canine and porcine coronary epicardial and resistance arteries. AB - Coronary resistance arteriolar diameter importantly regulates myocardial blood flow, and is influenced by circulating neurohumoral agents. Angiotensin II (A-II) is a circulating polypeptide that is chronically elevated in heart failure and serves as a potent peripheral vasoconstrictor agent. However, its effects on isolated coronary resistance arterioles is relatively unknown. We compared the vasomotor effects of A-II on coronary epicardial and resistance arterioles in vitro from both the canine and porcine heart in order to determine the effects of A-II in different vascular beds and species. Epicardial rings were studied under isometric recording conditions, while resistance arterioles (50-150 microns) were studied in vitro using a video imaging system to record diameter. A-II, whether applied to passively distended or preconstricted porcine resistance arterioles, did not cause vasoconstriction when applied as a bolus or as cumulative doses. In preconstricted canine resistance arterioles, A-II elicited dose-dependent vasodilation (EC50 = 0.2 nM). In passively distended canine arterioles, high concentrations of A-II (0.1 microM) applied as a bolus elicited transient vasoconstriction in 28% of the vessels studied. In large epicardial rings, A-II was a weak vasoconstrictor, with greater potency in canine arteries compared to porcine arteries. In canine arteries, vasoconstriction to A-II was augmented after incubation with indomethacin. In contrast to the findings in canine arteries, the A-II vasoconstrictor response in porcine coronary arteries was decreased after incubation with indomethacin or removal of the endothelium. Thus, A-II elicits the release of a vasodilator prostanoid in epicardial canine coronary arteries and a vasoconstrictor prostanoid in porcine vessels which modulate the vasomotor action of A-II.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7986959 TI - Non-hypertensive deoxycorticosterone-salt treatment accelerates atherosclerosis progression in Watanabe heritable hyperlipidemic rabbit. AB - Epidemiological studies have indicated that hypertension enhances the development of atherosclerosis in patients with lipid disorders. However, it was still unclear whether this promoting effect resulted only from hemodynamic changes or whether part of it was mediated by humoral or neurogenic factors independent of blood pressure alteration. The aim of this study was to determine whether mineralocorticoids, which are known to be involved in the pathogenesis of hypertension, could be implicated in the atherosclerotic process independent of pressure changes. For this purpose, the effect of deoxycorticosterone (DOCA, 200 mg/kg s.c.) on aortic atherosclerosis was studied in Watanabe heritable hyperlipidemic (WHHL) rabbits in comparison with New Zealand rabbits. After 4 weeks of treatment, DOCA significantly increased the size of atherosclerotic lesions in the arch and thoracic aorta (+115%) in parallel with the aortic cholesterol ester content (+83%). The vascular free cholesterol and triglyceride content remained unchanged on DOCA treatment, as were arterial pressure and plasma cholesterol levels. None of these effects was observed in New Zealand rabbits. DOCA did not accentuate the alteration of endothelial function usually found in WHHL rabbits. The sensitivity to serotonin was not altered, but the maximal contraction to this agonist was decreased in both strains by mineralocorticoid treatment. PMID- 7986960 TI - Stroke-prone SHR vascular muscle Ca2+ current amplitudes correlate with lethal increases in blood pressure. AB - Studies on the possible causal relationship between the Ca2+ channel current density in the vascular muscle cell (VMC) and increases in blood pressure were extended by a comparison of stroke-prone spontaneously hypertensive rats (SP-SHR) with N/nih outbred normotensive rats. Maximal amplitudes of both L-type and T type Ca2+ channel currents were significantly increased in SP-SHR without a difference in cell capacitance. SP-SHR peak current amplitudes in 20 mM Ba2+ averaged 446 +/- 64 pA while N/nih averaged 156 +/- 25 pA (clearly separated statistically). Both L-type and T-type Ba2+ currents (IBa) were significantly increased in SP-SHR, shown also by peak current frequency distributions. There was a significant shift to the left of both activation (7 mV) and inactivation (15 mV) current-voltage (I-V) plots. SP-SHR IBa recovery from inactivation was significantly slower (103 versus 61 ms) than in N/nih VMC. The increases in SP SHR IBa amplitude under maximized conditions correlated with increases in blood pressure. Together with earlier observations of increased vascular muscle Ca2+ current density coexistent with blood pressure elevation in Kyoto-Wistar SHR, these data provide evidence for altered function of Ca2+ channels as a fundamental component of hypertension. Since the Ca2+ channel alterations exist in venous VMCs of newborn SP-SHR rats (in a low pressure blood vessel and at a time when increased Ca2+ current density could not be an effect of increased blood pressure), our results add to the growing evidence of Ca2+ channel abnormalities as a cause of genetic hypertension. PMID- 7986961 TI - Review article: treatments that impact favourably upon the eradication of Helicobacter pylori and ulcer recurrence. AB - Healing the gastroduodenal mucosa through Helicobacter pylori eradication leads to a dramatic reduction in gastroduodenal ulcer relapse. Eradication of H. pylori proves to be difficult. Although the organism is sensitive to many antibiotics in vitro, the in vivo eradicating efficacy is often disappointing. This overview summarizes the most commonly used currently-available eradication schemes and the consequences of successful eradication in peptic ulcer disease. PMID- 7986962 TI - Review article: Helicobacter pylori eradication--understandable caution but no excuse for inertia. AB - The long-term management of patients with peptic ulcer disease is unsatisfactory, as judged by the persistently high levels of haemorrhage, perforation and death from this condition in Western countries. Although ulcer recurrence and complications can be prevented, many patients with peptic ulcer disease fail to receive the benefits of modern therapeutic regimens. In recent years, eradication of Helicobactor pylori has been promoted as a 'cure' for peptic ulcer disease and, while such claims are premature, there can be little doubt that this treatment--when successful--dramatically improves the medium-term prognosis of ulcer patients. However, in general, clinicians have given this promising therapeutic advance a lukewarm welcome. The aim of this detailed review of the literature is to remove the uncertainty and confusion surrounding many aspects of eradication therapy. Estimates are provided of the eradication rates after either triple therapy or the combination of omeprazole plus amoxycillin, and the sources of variation in published studies are discussed. Problems associated with eradication therapy, including side effects, compliance and re-infection, are addressed in order to ascertain the extent and clinical significance of each factor. In addition, studies reporting the outcome of patients with peptic ulcer disease after eradication are assessed with reference to both ulcer recurrence and complications. The result of the review is to dissipate much of the scepticism concerning eradication therapy. However, whilst acknowledging the efficacy of eradication therapy, its limitations have also to be recognized. By itself, it does not provide the complete answer to peptic ulcer disease. For some ulcer patients, eradication therapy is the preferred option; for others, prophylactic therapy with H2-receptor antagonists is more suitable. Guidelines are proposed for the selection of patients for each alternative therapy. The crucial point is that patients with peptic ulcer--excluding the small proportion with a mild form of the disease--require positive, long-term management consisting of either continuous prophylaxis with H2-receptor antagonists or the eradication of Helicobacter pylori. PMID- 7986963 TI - Review article: orthograde gut lavage for colonoscopy. AB - Most colon cleansing regimens for surgical and diagnostic procedures such as colonoscopy are modifications of older barium enema X-ray preparations which have evolved in gastrointestinal laboratories influenced by empiric experience. Recent formal study allows for careful comparison of gut lavage, diet and cathartic, and oral sodium phosphate preparations. This review will evaluate oral lavage solutions and address their safety, tolerance and efficacy. Administration options are discussed as well as other diet and cathartic methods previously referred to as 'standard preps'. PMID- 7986964 TI - A dose-response study of orally administered torsemide in patients with ascites due to cirrhosis. AB - BACKGROUND: This study evaluated the dose-response relationship of torsemide, the first pyridine-sulphonylurea loop diuretic, in patients with ascites due to cirrhosis. METHODS: During a 13-day hospitalization period, 17 patients received single, oral doses of 5 mg, 10 mg, or 20 mg of torsemide or placebo in a randomized, double-blind, crossover fashion. All the patients received a constant dose of spironolactone concomitantly beginning at least 7 days before the study. Electrolyte excretion and urine volume were measured for 24 h after each dose. Body weight was measured before, and 24 h after each dose. RESULTS: Torsemide was effective in producing statistically significant, dose-related increases in urinary sodium and chloride excretion, with little effect on potassium or magnesium excretion. Urine volume increased and body weight decreased in a dose related manner. CONCLUSION: Torsemide increased sodium excretion substantially in patients with cirrhosis and ascites who were receiving spironolactone. PMID- 7986965 TI - Alosetron does not affect the visceral perception of gastric distension in healthy subjects. AB - BACKGROUND: The effect of alosetron, a new specific 5-HT3 receptor antagonist, on the visceral perception in response to gastric distension was assessed in 12 healthy male subjects in a randomized, double-blind, placebo controlled crossover trial. METHODS: Each subject was given orally either alosetron 1 mg b.d. or placebo b.d. for 6 days (wash-out period 7-28 days). At the end of each dosing period, both isobarometric and isovolumetric gastric distensions were performed using an electronic barostat. RESULTS: Alosetron did not modify the gastric wall compliance (pressure-volume relationship). Alosetron had an effect similar to placebo on the visceral perception scores in both isobarometric and isovolumetric distensions. The mean (+/- SEM) thresholds for abdominal discomfort were, respectively, 16.8 +/- 0.7 mmHg and 825 +/- 61 mL with alosetron, 16.7 +/- 0.6 mmHg and 883 +/- 45 mL with Placebo (P = NS). CONCLUSIONS: 5-HT3 receptors do not appear to be involved in the visceral perception of gastric distension in healthy subjects. PMID- 7986966 TI - Antidepressant therapy in 138 patients with irritable bowel syndrome: a five-year clinical experience. AB - BACKGROUND: Antidepressant agents may have a therapeutic role in functional gastroenterologic disorders, but controlled investigations in irritable bowel syndrome (IBS) have not provided satisfactory practice recommendations. To help with future study design, we reviewed a five-year clinical experience with antidepressant agents in out-patients with IBS. METHODS: Presenting features, treatment course, and clinical outcome were determined from a chart review of 138 patients attending a university-based gastroenterology practice. RESULTS: Patients were treated with up to five antidepressants in separate, consecutive trials if a satisfactory end-point had not been reached. Tricyclic antidepressants were utilized 130 times, newer antidepressants 39 times, and anxiolytic-antidepressants 47 times. Improvement and complete remission in bowel symptoms occurred in 89% and 61% of patients, respectively, during antidepressant therapy. Median dosages being prescribed when remission occurred were less than those conventionally used in clinical psychiatry (50 mg/day for several tricyclic antidepressants). Age, gender, symptom duration, and presence of psychological symptoms did not discriminate those who remitted from those who did not, whereas a pain predominant symptom pattern was more commonly associated with symptom remission (P < 0.05 comparing symptom patterns). Symptom remission was more likely during the first antidepressant treatment than with subsequent trials in the group with continued symptoms (P = 0.01), but nearly half of the patients with side effects or no benefit from the first agent who went on to subsequent trials remitted during treatment with an alternative antidepressant. CONCLUSIONS: The design of this retrospective review is not capable of determining the efficacy of antidepressants for IBS. Our observations in conjunction with other available data suggest that future trials should employ low daily dosages, carefully assess pain response, include patients with and without active psychiatric symptoms, and utilize a second agent for subjects intolerant or unresponsive to the first. PMID- 7986967 TI - Ulceration, fibrosis and diaphragm-like lesions in the caecum of rats treated with indomethacin. AB - BACKGROUND: Patients on nonsteroidal anti-inflammatory drugs can develop curious intestinal fibrotic diaphragms. METHODS: Groups of rats received indomethacin mixed into a powdered diet at 3 mg.kg/day for 6 and 12 weeks and 6 mg.kg/day for up to 6 weeks. In an attempt to reproduce a human dosing regimen, another group of rats, for a total of 30 weeks, received consecutive periods of indomethacin at 3 mg.kg/day for 12 weeks, 4.5 mg.kg/day for 1 week, 6 mg.kg/day for 1 week, control diet for 6 weeks, 4.5 mg.kg/day for 2 weeks and finally, a control diet for a healing period of 8 weeks. Control rats received powdered diet alone. At termination, the small and large intestines were examined macroscopically and histologically. RESULTS: Indomethacin caused microcytic anaemia, hypoalbuminaemia, small intestinal ulceration, caecal ulceration and inconspicuous raised mucosal lesions in the caecum that histologically showed submucosal fibrosis with disruption and thickening of the apical muscularis mucosae. No control rats showed any abnormality. CONCLUSION: These fibrotic lesions of the rat caecum resemble human diaphragms and may arise from healed caecal ulcers. PMID- 7986968 TI - Topical anticolitic efficacy and selectivity of the glucocorticoid budesonide in a new model of acetic acid-induced acute colitis in the rat. AB - AIMS: To study the effect of local or parenteral administration of the glucocorticoid budesonide in the acetic acid-induced colitis model in the rat. METHODS: Colitis was induced in an exteriorized colonic segment by administration of 4% acetic acid for 15 s. Four days later, this colonic segment with colitis was examined using a morphological scoring system, and measurements of myeloperoxidase activity and of plasma exudation into the colonic segment. The experimental colitis showed morphological similarities to human ulcerative colitis, with 3-fold increase in myeloperoxidase activity and 6-fold increase in the plasma exudation. Budesonide in different doses administered for 3 days, starting one day after acetic acid instillation, prevented the development of colitis in a dose-dependent manner. The best effect of budesonide on the morphological score was achieved after local treatment at a dose of 10(-5) M twice daily (76% reduction compared with a control colitis group) and parenteral treatment with 0.75 mg/kg (80% reduction). These doses also normalized myeloperoxidase activity and significantly reduced the plasma exudation. The systemic effects of the drug were most pronounced in the group treated with parenteral budesonide. This group showed the greatest reduction in body weight and a significant reduction of the weight of adrenal glands and spleen (as compared to controls). Thymus weight in animals treated systemically was significantly lower than in locally treated animals. In the group treated with local budesonide the weight of adrenals was reduced. However, the weights of spleen and thymus were not reduced and the reduction of the body weight was even less than in the control group. CONCLUSION: Local treatment with budesonide at a dose of 10(-5) M (0.17 mg/kg if completely absorbed, but only 0.03 mg/kg with 15% bioavailability on colonic application) was as effective as parenteral treatment at a dose of 0.75 mg/kg in the attenuation of acetic acid-induced colitis in the rat, but resulted in minor systemic side-effects. PMID- 7986969 TI - A dose-ranging study of ranitidine and its effect on intragastric and intra oesophageal acidity in subjects with gastro-oesophageal reflux disease. AB - METHODS: This randomized, double-blind, single-centre, crossover study was designed to assess the effects of three regimens of ranitidine (150 mg b.d., 300 mg b.d. and 300 mg q.d.s.) and placebo on intra-oesophageal and intragastric pH in subjects with gastro-oesophageal reflux disease (GERD). Twenty-six subjects were screened, and 9 were evaluable by the admission criteria. These 9 subjects received each of the regimens for 72 h, and a wash-out period of at least 48 h followed each dosing period. Standard meals and beverages were provided. RESULTS: With increasing doses of ranitidine, 24-h intragastric mean H+ and integrated H+ fell, and the percentage of the time the pH was equal to or greater than 4 (% time pH > or = 4) rose: the minimum effective dose for these effects was ranitidine 300 mg daily. With increasing doses of ranitidine there was also a progressive decline in mean 24-h intra-oesophageal H+ and integrated H+, and increasing % time pH > or = 4. The minimal effective dose was 300 mg daily for intra-oesophageal mean H+ and integrated H+, and 600 mg for % time pH > or = 4. The minimal effective dose to decrease the number of reflex episodes was 1200 mg ranitidine. For the daytime upright position, a dose effect of increasing ranitidine was also seen, with minimal effective ranitidine doses of 300 mg for a decrease in mean H+, and 1200 mg for % time pH > or = 4. CONCLUSION: If these higher doses of ranitidine are confirmed to be more effective than the standard 150 mg b.d. regimen for the treatment of patients with gastro-oesophageal reflux disease, then the mechanism of this action probably relates to the lower exposure of the oesophageal mucosa to acid. PMID- 7986971 TI - The outcome of peptic ulcer haemorrhage in relation to consumption of nonsteroidal anti-inflammatory drugs or aspirin. AB - AIM: To compare the outcome of 76 patients who presented with severe peptic ulcer haemorrhage whilst taking nonsteroidal anti-inflammatory drugs (NSAIDs) or aspirin with that of 112 patients who were not taking these drugs and who developed peptic ulcer haemorrhage over the same time period. METHODS: The two groups of patients were managed identically and endoscopic therapy was attempted in all cases. RESULTS: The group taking NSAIDs or aspirin tended to be older and had a higher prevalence of cardio-respiratory disease. The severity of bleeding (as assessed by the presence of shock, anaemia and endoscopic stigmata) was similar in the two groups. Outcome in terms of uncontrolled haemorrhage, rebleeding and blood transfusion requirements did not differ significantly in the two groups. The NSAID group had a significantly longer duration of admission, almost certainly attributable to a higher prevalence of co-morbid diseases. CONCLUSIONS: Despite the deleterious effects of NSAIDs and aspirin upon renal and platelet function, the prognosis of peptic ulcer bleeding is not adversely affected by NSAID or aspirin therapy. PMID- 7986970 TI - Clarithromycin-amoxycillin therapy for Helicobacter pylori infection. AB - BACKGROUND: More convenient therapies are needed to treat Helicobacter pylori infection successfully. Clarithromycin and amoxycillin are effective against H. pylori both in vivo and in vitro. Recent success with a high dose amoxycillin metronidazole combination therapy led us to evaluate clarithromycin-amoxycillin dual therapy for H. pylori infection. METHODS: We tested the combination of clarithromycin 500 mg t.d.s. with meals plus amoxycillin 750 mg t.d.s. with meals for 10 days for its effect on H. pylori infection in 29 patients with documented H. pylori peptic ulcers. There were 27 men and 2 women, ranging in age from 23 to 77 years. H. pylori and ulcer status were evaluated at entry and at least 4 weeks after ending antimicrobial therapy. For ulcer healing, ranitidine 300 mg was given each evening for 6 weeks. H. pylori status was determined by CLOtest and histology. RESULTS: H. pylori infection was cured in 86% (95% CI = 78-99%). Compliance averaged 93% by pill count. Ten patients (34%) experienced mild side effects: eight reported dysgeusia and two had mild diarrhoea; none discontinued therapy because of side effects. CONCLUSION: We conclude that dual therapy with clarithromycin and amoxycillin is a safe and effective alternative regimen for the successful treatment of H. pylori infections. PMID- 7986972 TI - Inhibition of 5-hydroxytryptamine re-uptake impairs human gall-bladder emptying. AB - BACKGROUND: 5-Hydroxytryptamine (5-HT) is an important neurotransmitter in the enteric nervous system. The intrinsic neural plexus of the gall-bladder resembles the enteric nervous system and similarly contains 5-HT neurones. The action of 5 HT on gallbladder motility has been investigated in animals but its effect on the human gall-bladder in vivo is unknown. METHODS: The effect of indirect 5-HT agonism using paroxetine, a specific inhibitor of neuronal 5-HT reuptake, on gall bladder motility was investigated in 12 healthy volunteers. In a randomized double-blind crossover design, gall-bladder motility was assessed after administration of 30 mg paroxetine daily for two days and after placebo. Ultrasonography was used to determine gall-bladder volumes while fasting and at 5 min intervals following a 250 kcal mixed liquid meal. RESULTS: Fasting gall bladder volumes of 21.8 +/- 3.2 ml on placebo and 28.0 +/- 3.5 ml on paroxetine were similar. Paroxetine impaired postprandial gall-bladder emptying. Residual gall-bladder volume was 10.2 +/- 2.7 ml with placebo and 17.1 +/- 2.7 ml with paroxetine (P < 0.05). Ejection fraction was 57.3 +/- 7.7% on placebo and 40.9 +/ 4.7% on paroxetine (P < 0.05). CONCLUSION: 5-HT pathways may participate in the regulation of biliary motility, and this study demonstrates an inhibitory role of 5-HT in the control of human gall-bladder emptying. PMID- 7986973 TI - Steroid treatment in active Crohn's disease: a comparison between two regimens of different duration. AB - BACKGROUND: Steroids are highly effective in active Crohn's disease; clinical relapse following steroid withdrawal, however, is frequent. We used two steroid regimens of different duration in order to compare their efficacy in inducing and maintaining clinical remission. METHODS: Seventy patients with active Crohn's disease were treated with methylprednisolone 40 mg/day i.m. for 3 weeks and then with two different regimens of tapering dosage: one for a further 4 weeks and another for a further 12 weeks. RESULTS: Steroid therapy induced remission within 3 weeks in 91% of the whole group of patients; at the end of each protocol remission rates were 85% of patients in the group treated for the shorter period and 87% of those treated for the longer period (difference 2%, CI = -14 to 18, P = NS); remission rates within 6 months after stopping steroids were 53% and 37% respectively (difference 16%, CI = -9 to 41, P = NS). CONCLUSIONS: No significant differences were found between the two regimens. Multiple courses of steroid treatment in the previous 3 years and a short time interval following previous steroid treatment seem to be risk factors for relapse. PMID- 7986974 TI - Omeprazole, bismuth and clarithromycin in the sequential treatment of Helicobacter pylori infection. AB - AIMS: To assess the therapeutic potential of clarithromycin, a new macrolide with high anti-Helicobacter pylori activity, given with bismuth salts and omeprazole in different regimens aimed at simplifying the treatment of H. pylori-related gastritis. METHODS: Eighty-eight patients with proven H. pylori infection and gastritis were treated with one of the following four regimens: omeprazole 40 mg/day for one week (group A, n = 14); omeprazole 40 mg/day for one week followed by clarithromycin 1 g/day for 2 weeks (group B, n = 26); omeprazole 40 mg/day for one week followed by tripotassium dicitrato bismuthate 480 mg/day and clarithromycin 1 g/day, both for two weeks (group C, n = 26); and tripotassium dicitrato bismuthate 480 mg/day and clarithromycin 1 g/day for two weeks (group D, n = 22). Presence of H. pylori, histology and electron microscopy were assessed at entry and four weeks after the end of each treatment. RESULTS: Omeprazole alone had no effect on H. pylori status. The highest eradication rate was obtained in group C patients (81%), a proportion significantly greater than that observed in group B (50%, P < 0.03) or group D patients (55%, P < 0.05). CONCLUSION: Sequential treatment may be a useful option in the treatment of H. pylori-related gastritis. PMID- 7986975 TI - Clinical trial of omeprazole in patients with Barrett's oesophagus. PMID- 7986976 TI - [More diagnostic technology for primary care]. PMID- 7986977 TI - [Antibiotics in the treatment of peptic ulcer]. PMID- 7986978 TI - [Characteristics of the patient overusing on-demand general medical services]. AB - OBJECTIVE: To determine the characteristics and reasons for consultation of the patient who over-uses on-demand general medical services. DESIGN: A case-control study of a sample of over-user patients and a control group of normal users. SETTING: The Chantrea Health Centre in Pamplona during 1991. PATIENTS AND OTHER PARTICIPANTS: An age and gender-stratified sample of 411 over user patients and a control group of normal users were selected. MAIN MEASUREMENTS AND RESULTS: Over users corresponded to 5% to those attending. We found no significant differences for gender, but we did for age (p < 0.001), regarding the control group; 84% of over-users had a chronic associated pathology. Comparatively, over-users made more bureaucratic and prescription visits (35%) and attended less scheduled appointments. CONCLUSIONS: The over-users is associated to being older and especially to having a chronic pathology and not attending scheduled appointments. PMID- 7986979 TI - [Validation of an automatic noninvasive arterial pressure monitor: the ACP-2200]. AB - OBJECTIVE: To check the validation of the precision in measuring arterial pressure (AP) of an automatic non-invasive machine for out-patient monitoring of arterial pressure, the ACP-2200, comparing the sequential with the simultaneous method in line with the criteria of the Association for the Advancement of Medical Instrumentation. DESIGN: A comparative crossover study. SETTING: Primary Care. "La Orden" Health Centre, Huelva. PATIENTS: 86 individuals, 42 men and 44 women of all ages, both hypertense and not, and without any antihypertension treatment, with SAP intervals between 99 and 160 mmHg and DAP between 59 and 105 mmHg, selected at random from the on-demand consultations. MEASUREMENTS AND MAIN RESULTS: Three AP readings were made with a manual apparatus for reference (a mercury sphygmomanometer) and three simultaneously with the ACP-2200 and the manual apparatus placed in a T on the cuff. The AP means obtained were compared and the mean calculated. The standard deviations of the paired differences between the APs obtained with the ACP-2200 and with the manual method, both in the sequential and simultaneous form, as well as Pearson's lineal correlation coefficient, were all calculated. The means of the paired differences and the standard deviations between the automatic and manual apparatuses were, for the SAP, 1.52 +/- 4 (r = 0.96) and 0.66 +/- 3.38 (r = 0.97) (sequential and simultaneous, respectively) and, for the DAP, 0.86 +/- 2.84 (r = 0.98) and 0.64 +/- 1.73 (r = 0.99) (sequential and simultaneous, respectively). All the values of p were inferior to 0.001. CONCLUSIONS: The ACP-2200 complies with the validation criteria for the two methods used, with the simultaneous method being recommended for use. PMID- 7986980 TI - [Control of arterial hypertension: analysis of visit and time factors]. AB - OBJECTIVE: To analyse the frequency of attendance and the time elapsed between the diagnosis of Arterial Hypertension (AHT) and the control of Arterial Pressure (AP); and to analyse the different ways of presenting the level of control of AHT. DESIGN: Retrospective study. SETTING: Teaching Health Centre. PATIENTS: 103 hypertense patients diagnosed since 1986: 44 men (42.7%) and 59 women (57.3%), with an average age of 52.6 +/- 1. Their initial AP was 164.4 +/- 17.1/102.1 +/- 7.4 mmHg. The criterion of AHT control was Diastolic Arterial Pressure (DAP) < 90 mmHg. MEASUREMENTS AND MAIN RESULTS: AP at the end of the first year was 150.1 +/ 20.6/90.7 +/- 9.6 mmHg (p < 0.001 in comparison with the initial AP). The average attendances for AHT and per patient in the first year was 8.7 +/- 5 (1 26). Patients with more severe forms of AHT and/or with associated risk factors visited more often (p < 0.05). During the first year 76 patients (73.7%) presented on at least one attendance a controlled DAP. At the end of the first year 46 patients (44.6%) were under control. The average time per patient until AP was controlled was 28.6 +/- 31.6 weeks (1-168). Males and under-65s took more time to control their AP (p < 0.05). CONCLUSIONS: There are gender and age differences in the time required to bring AP under control. Frequency of attendance is related to the severity of AHT and the presence of other pathologies and risk factors. The level of control of AHT, expressed in different ways, is not constant. PMID- 7986981 TI - [Primary care as a determinant of the utilization of hospital emergency services]. AB - OBJECTIVE: To study the characteristics of emergency care within Primary Care (ECPC), which determine the use of hospital emergency services (HES). DESIGN: Retrospective study. The unit of analysis was the patient attended at the HES. SETTING: Xativa Hospital records and data from Primary Care Management, regarding the type of ECPC and the distance from the patient's town of residence to the hospital. PATIENTS AND OTHER PARTICIPANTS: The data of all the patients, a total of 15,290 cases, attended at the HES during the first six months of 1992 were analysed. MEASUREMENTS AND MAIN RESULTS: We constructed a logistic regression model whose explicative variables were the type of ECPC and the distance to the hospital. The variable reply was the probability for each town of causing a high use of HES. We obtained a model whose predictive capacity was 82.98%, in which, independently of distance, the probability of causing a high use of HES was ordered from low to high, as follows: 1) Towns where the Primary Care Team (PCT) physically provided ongoing care in the town itself. 2) Towns attended by a normal Emergency Service (in the town itself). 3) Towns where the PCT provided ongoing care of a localised nature. 4) Towns where the PCT physically provided ongoing care in another town. The relation of distance to the use of HES was inverse. CONCLUSIONS: Distance and the different types of ECPC affect the use of HES. PMID- 7986983 TI - [Dietary habits during lactation in the Llerena (Badajoz) health area]. AB - OBJECTIVE: To analyse the feeding habits used for nursing children in the Llerena Health Area (Badajoz). DESIGN: A descriptive and inferential study, using questionnaires given to the mothers. SETTING: Schools chosen at random from the eight health districts which make up the above-stated Health Area. PATIENTS AND OTHER PARTICIPANTS: Mothers (N = 369) of school-children in the first to eighth years of EGB (basic) for the 1991-2 school year. MEASUREMENTS AND MAIN RESULTS: We studied the type of feeding used, finding 29.15% exclusive breast-feeding, 46.5% mixed and 24.2% bottle. We investigated the average time of breast-feeding (4.7 months) and how supplementary feeding (Beikost) was started: usually with cereals (at 4.7 months), fruit (5.16 months) and vegetables, meat and fish (7.27 months). We found that advice on the lacteal preparation used for mixed and bottle lactation was provided by health professionals in 84.2% of cases and in lay persons, 15.8%. The most common reasons for stopping breast-feeding were Hypogalactia in 64.6% of cases and work in 23.1%. There was more exclusive breast feeding in the lowest socio-economic classes (p < 0.05) and among older mothers (p < 0.05). CONCLUSIONS: Findings were satisfactory concerning the way these children were milk-fed and the introduction of supplementary feeding. We noted a tendency in favour of breast-feeding. The social and work-related changes in womens' lives are having a decisive influence on the feeding practices of nursing children. PMID- 7986982 TI - [Analysis of direct costs of controlling arterial hypertension]. AB - OBJECTIVE: To analyse the number of attendances and the direct cost of pharmaceutical prescription arising from a year-long monitoring of hypertense patients. SETTING: Health Centre. DESIGN: A prospective observation study. PATIENTS: 220 hypertense patients, undergoing arterial pressure (AP) monitoring, were chosen by means of systematic random sampling. MEASUREMENTS AND MAIN RESULTS: The variables of age, gender, cardiovascular risk factors, AP, monitoring level (criterion AP < 160-90 mmHg), attendances and treatment used were analysed. The pharmaceutical cost was calculated in line with the dosages and according to the 1990 Vademecum. The monitoring level was 43.6%. The total number of attendances per patient were 12.8 +/- 6.43 and those for hypertension, 7.9 +/- 3.5. Diabetics attended more for hypertension (8.8 vs 7.5, p < 0.05). Pharmaceutical treatment was prescribed for 183 people (83.2%). The number of drugs was correlated with the severity of the hypertension and the number of attendances. Overall drug cost was 429,571 pesetas per month. Average monthly cost per patient was 2,348.69 +/- 2,318.92 pesetas (range 90.5-12,856.5). Angiotensin enzyme conversion inhibitors (AECI) made for the greatest monthly mean cost per patient (4,352.9 pesetas) and diuretics, the least (322.2 pesetas). CONCLUSION: Frequency of attendance is related to the presence of diabetes and the number of drugs prescribed. The introduction of AECI and Calcium antagonists into first-line treatment represents an important increase in the cost of controlling Hypertension. PMID- 7986984 TI - [Tobacco consumption among primary care physicians in the Autonomous Community of the Basque Province]. AB - OBJECTIVE: To discover the tobacco consumption among Primary Care doctors in the Autonomous Community of the Basque Country. DESIGN: A crossover study by means of a telephone survey. PARTICIPANTS: 285 Primary Care doctors in the Autonomous Community of the Basque Country, obtained by systematic random sampling. RESULTS: Out of the 275 doctors who were finally surveyed, 32.1% smoked every day. 47.4% of doctors between 45 and 64 years old defined themselves as ex-smokers. CONCLUSIONS: The hypothesis can be ventured that Primary Care doctors are in the vanguard of giving up tobacco consumption. PMID- 7986985 TI - [New antimicrobial agents in pediatric primary care]. PMID- 7986986 TI - [Ethics in general medicine practice: a pending subject matter]. PMID- 7986987 TI - [Domiciliary care: a study previous to the implementation of a program]. PMID- 7986988 TI - [Towards a competitive market?]. PMID- 7986989 TI - [Adolescence and contraception]. PMID- 7986990 TI - [Reply to the invitation to participate in a multicenter study EIBAL]. PMID- 7986991 TI - [The significance of the significant. Some considerations on the use of the value "p"]. PMID- 7986992 TI - [Network of health research services]. PMID- 7986993 TI - [Service demand flow and planning in primary care]. AB - OBJECTIVE: We wish to know the moment from which people first came into contact with general practitioners in Primary Care and which socio-demographic variables influence this. DESIGN: Prospective, observational study. SETTING: Primary Care, general practitioners. PARTICIPANTS: 469 people newly registered with a general practitioner. Follow-up study is 12 months. MEASUREMENTS AND MAIN RESULTS: We have made a Kaplan-Meier survival analysis and a comparison of curves with a log rank test. 50% of population visit for the first time during the fourth months following their registration. 75% of newly-registered of people attend at least once during the first year following registration. Women are more likely to attend than men (p < 0.001), people older than 53 years of age (p < 0.001) and young people with chronic health problems (p < 0.01) are also more likely to visit the doctor than others. CONCLUSIONS: At least one time at year had attended 75% of people of new registration in Primary Care. Women, people older than 53 and young people with chronic health problems attend before. This observation leads us to begin the "finding case" strategy as a screening method, to use this fact to instigate prevention activities, health education campaigns and to avoid overburdening the workload, in order to manage services request. PMID- 7986994 TI - [Accessibility to hospital pediatrics emergencies: distance and diagnostic resources]. AB - OBJECTIVE: To study the justification of paediatric consultations in the hospital emergency services in line with the diagnosis, the need for further tests not available in primary care (PC), the need for admission or observation and the distance between home and casualty. DESIGN: A descriptive study assessing 2,906 emergency records forms. We used the chi-squared test for the statistical analysis. The extent of the associations was calculated using the odds ratio (OR) calculation. SETTING: Casualty department in the Nuestra Senora de Candelaria Hospital in Santa Cruz de Tenerife. PATIENTS AND OTHER PARTICIPANTS: Those patients between 0 and 14 attended at the casualty department. MEASUREMENTS AND MAIN RESULTS: The 80% of the patients lived closer than 10 kilometres to the hospital. The 39.8% attended because of a trauma. The 55% of attendances were considered unjustified. The fact that 70% of the traumatic injuries required an X Ray (OR = 7) led to our establishing significant differences (p < 0.0001) between the proportion of justified consultations caused by trauma and by other reasons. The consultations by patients who lived over 10 km from the hospital were significantly more justified (p < 0.0001). CONCLUSIONS: The absence of radiological facilities in primary care emergency services means that patients with traumatic injuries have to attend hospital despite the triviality of the great majority of cases. Closeness to hospital facilities causes not only greater use of these, but a greater number of unjustified attendances. PMID- 7986995 TI - [Role of the primary care physician in the diagnosis and treatment of thyroid diseases]. AB - OBJECTIVE: To determine the participation of the primary care physician in the diagnosis and follow-up of thyroid pathology. DESIGN: A descriptive study of a crossover type. SETTING: The Isabel II Health centre at Parla (Madrid). PATIENTS: All those diagnosed with thyroid pathology registered with the two primary care teams at the Isabel II Health Centre up to august 1992. Data were obtained from the morbidity records and the District's Endocrinology Clinic. MAIN RESULTS: 196 patients, with 250 diagnoses overall, were located. The main ones were: hypothyroidism (27.6%), normally functioning goitres (24.4%) and hyperthyroidism (23.2%). The general practitioner was aware of the illness in 87% of cases, as against the specialist in 97%. The provisional diagnosis was carried out at the primary care level in 56% of cases; the final one only in 18%. With respect to patients' subsequent treatment, it was exclusively specialist in 72% of cases and joint in 19%. CONCLUSIONS: The primary care doctor is aware of the majority of his/her patients' thyroid illnesses, but not all. We recommend greater participation of primary care in the initial diagnostic approach to these conditions; and, in particular, a closer involvement in the treatment of these pathologies, which requires that the primary care doctor must have access to precise diagnostic methods. PMID- 7986996 TI - [Referrals from primary care to pneumology: influence of attendance patterns and specialisation]. AB - OBJECTIVE: To study the number and quality of the referrals from primary care to pneumology. To analyse their relationship to specialist medical training and the attendance pattern. DESIGN: A descriptive, retrospective study. SETTING: A Pneumology Clinic at the Peripheral Specialities Centre at Cartuja (Granada). PATIENTS AND OTHER PARTICIPANTS: 597 referrals were gathered. These were for all the patients referred from primary care to this clinic from may to december 1992. MEASUREMENTS AND MAIN RESULTS: The overall population referral rate per 100,000 inhabitants and month of study was 39.73. The out-clinic doctors referred twice as many patients as health centre (HC) doctors, with OR = 2.01 (1.70 < OR < 2.36). Taken together, general physicians referred three times more than family doctors, with OR = 3.04 (2.54 < OR < 3.78). Regarding the quality of the referral documents, HC doctors accompanied a referral with sufficient information eleven times more often than out-clinic doctors, with OR = 11.38 (6.13 < OR < 21.47). Family doctors contributed this "correct" information thirteen times more often than general physicians without specialist training: OR = 13.50 (8.06 < OR < 22.67). CONCLUSIONS: The number and quality of referrals appear to be closely related to the attendance pattern and in particular to the specialist training of health professionals. PMID- 7986997 TI - [Hypertension programs and the risk of ischemic cardiopathy]. AB - OBJECTIVE: To find the risk of ischaemic cardiopathy in a sample of hypertension patients. DESIGN: Crossover study. SETTING: Almanjayar and Cartuja Health Centres (Granada). PATIENTS AND OTHERS TAKING PART: 202 Hypertension patients included in the programme and belonging to three practices in the above-mentioned centres. MEASUREMENTS AND MAIN RESULTS: We determined the variable of age, gender, overall cholesterol, cholesterol-HDL, TAS, HVI in ECG and we recorded the number of check ups over the last year, tobacco consumption and diabetes. The 47% of men and 46% of women presented a RCI higher than that of the population as a whole for their age and gender group, in spite of treatment and intervention on these risk factors. Men between 45 and 64 presented higher RCI than women (p < 0.001) and had fewer check-ups. CONCLUSION: We consider that our programme did not sufficiently affect the prevention of ischaemic cardiopathy. It was especially deficient in the monitoring of men between 45 and 64 years. We think that the maintenance of programmes oriented round particular pathologies, instead of integrated programmes, is not sufficient to reduce ischaemic cardiopathy, which clearly has a multiple-cause origin. PMID- 7986998 TI - [Prevalence of asymptomatic carriers of pathogenic germs in the nasopharynx. Comparison made between primary health care professionals and the population seeking care]. AB - OBJECTIVE: To determine if the prevalence of non-symptomatic nasopharyngeal carriers of pathogenic germs is higher in health workers of primary care than in the general population. DESIGN: Cross-sectional, observational study. SETTING: Primary Care. Salamanca Urban Area. PARTICIPANTS: Seventy-six Health Centre workers from Salamanca and 152 individuals representing the general population attending the Health Centers were studied. People with pathology related to the study subject or with inmunitary problems were excluded. MEASUREMENTS AND MAIN RESULTS: A nasopharyngeal sample was carried out using a swab. The relative prevalence of carriers (sanitary workers vs general population) was 0.38 (c.i. 0.20-0.72) for Staphylococcus aureus and 0.56 (c.i. 0.34-0.93) for all pathogens. No significant differences were found according to sex. CONCLUSIONS: The prevalence of non-symptomatic nasopharyngeal carriers is higher in general population than in the group of primary care workers. PMID- 7986999 TI - [Medical advice: secondary prevention of problems related to excessive alcohol consumption]. PMID- 7987000 TI - [What are QALYs? Quality adjusted life years]. PMID- 7987001 TI - [Usefulness of the clinical notes and the measurement of maximum expiratory flow in the evaluation of asthmatics]. PMID- 7987002 TI - [Topical minoxidil and accompanying migraines]. PMID- 7987003 TI - [Optic neuritis appearing during treatment with clomiphene]. PMID- 7987004 TI - [Suspected temporal arteritis in primary care]. PMID- 7987006 TI - European Association of Cardiothoracic Anaesthesiologists (EACTA) 9th annual meeting. June 1-4, 1994, Turku, Finland. Abstracts. PMID- 7987005 TI - British Society for Clinical Cytology. Programme and abstracts of the 33rd annual scientific meeting. Exeter, UK, 18-21 September 1994. PMID- 7987007 TI - Cloning and nucleotide sequence of a region of the Kibdelosporangium aridum genome homologous to polyketide biosynthetic genes. AB - The actinomycete Kibdelosporangium aridum naturally produces ardacin, a new glycopeptide antibiotic, the biosynthetic pathway of which should involve the participation of a polyketide synthase (PKS). A K. aridum 2.9 kb BamHI genomic fragment homologous to actI (a locus of the PKS cluster catalyzing polyketide chain assembly for actinorhodin biosynthesis in Streptomyces coelicolor) was isolated by shotgun cloning. This DNA fragment, called ardI, was sequenced and the deduced protein products were compared with those of other polyketide synthase genes, revealing similarities ranging from 50 to 80%. ardI was further used to probe a cosmid library of the K. aridum genome. Three hybridizing cosmids were obtained which contain overlapping inserts, together covering a 50 kb region, and including, 15 kb away from ardI, a fragment homologous to actIII, which codes for the ketoreductase of the actinorhodin PKS of S. coelicolor. All these findings indicate that at least part of a polyketide biosynthetic gene cluster has been isolated from the genome of the ardacin producer K. aridum. PMID- 7987008 TI - The rhesus macaque beta 1-adrenergic receptor gene: structure of the gene and comparison of the flanking sequences with the rat beta 1-adrenergic receptor gene. AB - We have cloned the gene for the rhesus macaque beta 1-adrenergic receptor. In addition to the protein coding block, we have sequenced its 5' (1424 bp) and 3' (1534 bp) flanking regions and aligned them with comparable sections of the rat beta 1-adrenergic receptor gene. The rhesus macaque gene contains a 1440 bp open reading frame which codes for a deduced protein of 480 amino acids that is 95% and 89% similar to the human and rat beta 1-adrenergic receptors, respectively. The rhesus macaque beta 1-adrenergic receptor contains conserved sites for potential N-linked glycosylation and cAMP-dependent protein kinase phosphorylation identified within the human and rat receptors, but differs in the structure and length of the third cytoplasmic loop. The 400 bases of 5' flanking sequence proximal to the protein coding block are highly conserved (84% similarity) between the rat and rhesus macaque genes. The entire 3' flanking sequence, which extends beyond two potential polyadenylation sites at 1050 and 1337 bp relative to the translation termination codon, is also highly conserved between the two species. Comparison of the flanking sequences of the two species reveals conserved regulatory sequences which may be important for beta 1 adrenergic receptor expression and transcriptional modulation. PMID- 7987009 TI - Nucleotide and deduced amino acid sequence of human cysteinyl-tRNA synthetase. AB - We have determined the nucleotide sequence of a cDNA coding human cysteinyl-tRNA synthetase. The predicted protein sequence of 638 amino acids has substantial sequence similarity to the E. coli cysteinyl-tRNA synthetase in the nucleotide binding fold region that constitutes the potential active site. The results are consistent with the hypothesis that evolution of the full complement of aminoacyl tRNA synthetases occurred prior to the divergence of prokaryotes and eukaryotes. PMID- 7987010 TI - Sequence patterns and hybridization analysis of clones generated by Alu-PCR. AB - A series of clones from an Alu-PCR library were analysed in more detail. Characterization by Southern blot hybridization and sequencing displayed several features common to all probes generated by this approach: Short length of the PCR products as well as the presence of homologous regions on both ends resulted in a limited feasibility for filter hybridization and a low probability of restriction length polymorphisms. In addition, a series of different short repeats at the 3' ends of Alu-repeats and present in the generated probes offers a rich source of potential variable sites accessible by PCR. PMID- 7987011 TI - A high throughput system for the preparation of single stranded templates grown in microculture. AB - A high throughput system for the preparation of single stranded M13 sequencing templates is described. Supernatants from clones grown in 48-well plates are treated with a chaotropic agent to dissociate the phage coat protein. Using a semi-automated cell harvester, the free nucleic acid is bound to a glass fiber filter in the presence of chaotrope and then washed with ethanol by aspiration. Individual glass fiber discs are punched out on the cell harvester and dried briefly. The DNA samples are then eluted in water by centrifugation. The processing time from 96 microcultures to sequence quality templates is approximately 1 hr. Assuming the ability to sequence 400 bases per clone, a 0.5 megabase per day genome sequencing facility will require 6250 purified templates a week. Toward accomplishing this goal we have developed a procedure which is a modification of a method that uses a chaotropic agent and glass fiber filter (Kristensen et al., 1987). By exploiting the ability of a cell harvester to uniformly aspirate and wash 96 samples, a rapid system for high quality template preparation has been developed. Other semi-automated systems for template preparation have been developed using commercially available robotic workstations like the Biomek (Mardis and Roe, 1989). Although minimal human intervention is required, processing time is at least twice as long. Custom systems based on paramagnetic beads (Hawkins et al., 1992) produce DNA in insufficient quantity for direct sequencing and therefore require cycle sequencing. These systems require custom programing, have a fairly high initial cost and have not proven to be as fast as the method reported here. PMID- 7987012 TI - Nucleotide sequence of the gene for peptostreptococcal protein L. AB - A gene bank of Peptostreptococcus magnus DNA was established using an E. coli host-vector system. Western blot analysis identified a clone expressing protein L which bound to the light chain of human immunoglobulins. DNA sequence determination and analysis revealed an open reading frame of 992 amino acids, giving a theoretical secreted protein of 106 kD with a pl of 4.67. PMID- 7987013 TI - Nucleotide sequence of the 85B-protein gene of Mycobacterium bovis BCG and Mycobacterium tuberculosis. AB - We have cloned and sequenced the genes coding for the 85B antigen from M. bovis BCG and M. tuberculosis. Within this gene, the only difference in sequence between M. bovis BCG and M. tuberculosis corresponds, respectively, to a C-->T yielding a Leu-->Phe replacement at position 100 of the mature 85B protein. Therefore as we described previously for the 85A gene, there is also very little variation between these two species within the 85B gene. PMID- 7987014 TI - A putative ATP-binding protein from the che/fla locus of Bacillus subtilis. AB - A majority of the chemotaxis and flagellar genes of Bacillus subtilis are found in the major che/fla operon which spans over 26 kilobases of DNA and encodes at least 30 genes. In this operon, a single open reading frame, designated orf298, has been demonstrated to encode a 33,131 Dalton protein which shows no evidence of being involved in chemotaxis or motility. A strain disrupted in orf298 was assayed for motility and chemotaxis and always behaved as the wild-type strain. Inspection of the translated sequence revealed a consensus ATP-binding region. While the role of ORF298 has not yet been determined, ATP-binding and/or hydrolysis is a likely function. PMID- 7987015 TI - Nucleotide sequence of ovine thioredoxin cDNA. AB - We report the cloning of an ovine thioredoxin cDNA. The clone was isolated from a bovine leukemia virus-infected cell line (FLK) cDNA library cloned in the lambda gt11 vector. The clone encodes the full length thioredoxin protein made of 105 amino acids with 92 and 83% identity to published sequences of human and mouse thioredoxin, respectively. PMID- 7987016 TI - Efficacy of the cued-listening task in the evaluation of binaural hearing aids. AB - To evaluate the efficacy of the cued-listening task (CLT) in the evaluation of binaural hearing aid performance, we tested 10 experienced binaural hearing aid users. Subjects listened for a speech target embedded in continuous discourse from either the right or left directions while simultaneously suppressing similar continuous discourse from the other direction. The task was carried out in the presence of multitalker babble from an overhead source. The target-to-babble ratio was always 0 dB. Testing was carried out in four conditions: (1) unaided; (2) aided in right ear; (3) aided in left ear; and (4) aided binaurally. Results showed that neither condition of monaural amplification was significantly better than the unaided condition. Under binaural amplification, however, there was a significant improvement in target recognition. Furthermore, this enhancement in performance was significantly greater when targets came from the right side than when they came from the left side. PMID- 7987017 TI - Variables to consider when interpreting the impact of monaural amplification. AB - A theoretical basis is presented for considering the current data available regarding the impact of monaural amplification over time and for the design of future prospective studies. We present a summary of essential subject parameters, amplification parameters, and test properties to be considered in this expanding area of investigation. This paper attempts to create a context in which to evaluate current findings and a framework in which to ground future investigations. PMID- 7987018 TI - Development of hearing. Part I: Phylogeny. AB - We humans hear the way we do because of at least three major forces. The first is phylogeny, the evolutionary changes in the auditory system since its beginnings. Another is embryology, the development of the system in each individual before birth. Finally, there is the biologically determined auditory mechanism we are born with and our interaction with the environment in early postnatal life. This series of three articles reviews each aspect in turn, so we may have a fuller appreciation of how it is we come to hear the way we do. Part I reviews the evolution of human hearing through the vertebrates. Ancestral bony fish had an equilibrial organ, which was passed to subsequent classes. Both amphibians and reptiles evolved their own auditory systems based on a balance organ inherited from fish. Amphibians independently evolved an impedance-matching apparatus through a combination of eardrum and ossicle. Reptiles evolved a flexible basilar membrane for the receptor cells. Mammals added movable, external ears and expanded the frequency response range. Finally, large-brained Homo acquired the use of language. Part II examines embryologic development and Part III considers postnatal aspects of auditory development. PMID- 7987019 TI - Early indicators of hearing conservation program performance. AB - Retrospective analysis of initial audiograms from 21 hearing conservation programs (HCPs) revealed several statistical protocols capable of identifying HCPs of known performance. American National Standards Institute (ANSI) and Occupational Safety and Health Administration (OSHA) protocols clearly identified 3 HCPs known to have demonstrated excellent overall programs. ANSI and OSHA outcomes appeared equivalent in ability to provide early warnings of potentially unacceptable HCP practices. PMID- 7987020 TI - Acoustic and hearing aid circuit variables affecting the tolerability of aided impulsive-type sounds. AB - The tolerability of aided impulsive-type stimuli was investigated in a group of 13 hearing-impaired listeners. Two linear circuits (one with a class A and one with a class D output stage) and one adaptive frequency response (AFR) circuit (with a class D output stage) were investigated. In a three-way paired-comparison task, subjects chose the hearing aid that was most tolerable when 75 dB sound pressure level (SPL) impulsive-type sounds were presented. Real-ear measurements of rms SPL, peak SPL, crest factor, and spectral distribution were made to determine which of these variables was most closely associated with behavioral tolerability scores. Results indicated significant differences across hearing aids for tolerability scores, rms sound pressure levels, and spectral peak frequencies. Highest tolerability scores were associated with the hearing aid that produced the lowest rms sound pressure levels in the ear canal (class D AFR). Significant correlations were found between tolerability and both rms SPL and peak SPL. Results are discussed in terms of circuit algorithm and in terms of the possible effects of hearing aid saturation. PMID- 7987021 TI - Relationship between in-situ distortion and hearing aid benefit. AB - In-situ hearing aid distortion is defined as distortion measured in the ear canal with stimulus inputs and hearing aid settings that are similar to those the hearing aid wearer will experience in daily life. This preliminary study examined possible relationships between in-situ distortion and benefit for appropriately fitted contemporary hearing aids. Simulated in-situ distortion was determined for 97 hearing aid fittings, divided among three typical listening environments: living room, classroom lecture, and social event. Measures included intermodulation, harmonic, and transient distortion. Overall results of between- and within-subject analyses of data suggested that there was a significant relationship between distortion and benefit in both reverberant and noisy environments similar to a classroom lecture and a social event, respectively. This outcome was seen despite the fact that distortion was quite low in absolute terms. Analyses also suggested that in-situ harmonic distortion was most closely related to benefit and that the other types of distortion measured did not make additional contributions to benefit prediction. We propose that measurements of in-situ harmonic distortion might be a valuable addition to hearing aid evaluations. PMID- 7987022 TI - Utilization of a questionnaire to provide follow-up services in an infant hearing screening program. AB - An important goal of any neonatal hearing screening program is to provide adequate monitoring and follow-up services for all newborns tested. This is often the most difficult component of the program to administer. An attempt was made to obtain follow-up information through the use of a questionnaire modeled after Jacobson and Jacobson (1990). This questionnaire was administered by mail or telephone to 119 parents whose infants had passed a hearing screening as neonates in four hospitals. Forty-four percent of all parents contacted by either means responded to the questionnaire; however, response rates varied by as much as 36 percent, depending on the hospital in which a child was born. Our results suggest that the successful use of follow-up questionnaires depends greatly upon hospital demographics. When limitations are considered, however, they may provide an alternative to on-site follow-up services for infants who pass initial screening. PMID- 7987023 TI - Cortical deafness: a longitudinal study. AB - We have studied a patient with MRI-confirmed bilateral absence of considerable portions of her temporal lobes resulting in cortical deafness. Although physiologic measures demonstrate normal peripheral hearing sensitivity, this patient's speech has the inflection and prosodic characteristics associated with profound peripheral hearing loss, and she is unable to understand spoken communication. Behaviorally obtained pure-tone thresholds taken over nearly 20 years range from normal to moderate hearing loss with normal middle ear muscle reflexes and normal ABRs; however, we consistently found abnormal middle latency and cortical evoked potentials. Because of her total inability to communicate auditorily, this patient was ultimately taught American Sign Language and educated at the Louisiana School for the Deaf. This rare case highlights the importance of using multiple audiologic measures sensitive to abnormalities at various levels of the auditory system. PMID- 7987024 TI - Acoustic neuroma in an adolescent without neurofibromatosis: case study. AB - When acoustic neuromas are found in younger age groups, they are typically bilateral and associated with neurofibromatosis (NF). A unilateral acoustic neuroma in a child or adolescent without NF is rare. We report audiometric, auditory brainstem response (ABR) and magnetic resonance imaging (MRI) data for a 15-year-old male with an acoustic neuroma but without associated NF. The patient was seen for audiologic assessment on three separate occasions over a period of 5 years. The first two assessments produced unremarkable audiometric and immittance data. The third assessment, subsequent to a failed school hearing screening, demonstrated a flat unilateral sensorineural hearing loss, unilateral absent acoustic reflexes, and abnormal bilateral ABR recordings. MRI with contrast demonstrated a unilateral mass extending out of the internal auditory meatus. Microscopic examination of the removed tumor confirmed a vestibular schwannoma. An enhanced MRI 3 years post neuroma removal demonstrated no evidence of tumor regrowth and no evidence of other neoplasms. ABR recordings for the uninvolved ear continued to demonstrate neural synchrony as evidenced by normal absolute wave latencies; however, the III-V and I-V interwave latencies remained extended beyond the 99th percentile. Postoperatively, the young man was fitted with a high gain in-the-ear hearing aid in the involved ear, which he has continued to wear on a daily basis for the past 3 years. PMID- 7987026 TI - Hypertension. PMID- 7987025 TI - Inappropriate use of term "saturation". PMID- 7987027 TI - Diseases of the aorta, pulmonary, and peripheral vessels. PMID- 7987028 TI - Newer thinking on the hemodynamics of hypertension. AB - For more than 30 years there has been general agreement that in the established phase of essential hypertension, the cardinal hemodynamic disturbance is an increased total peripheral resistance with cardiac output normal during rest, but subnormal during exercise. However, there are still different opinions about the hemodynamics in the starting phase of essential hypertension. Several studies from 1993--mainly performed in the offspring of hypertensive parents--reported high as well as low cardiac index values, depending on the patient selection and the methods used. Irrespective of whether the early phase of essential hypertension is caused primarily by increased cardiac output or increased total peripheral resistance, an increased sympathetic activity is usually held responsible for either hemodynamic disturbance. Simultaneous recordings of central and regional hemodynamics and sympathetic nerve traffic in young subjects with mild hypertension did show increased cardiac output, reduced calf blood flow, and increased nerve traffic as the characteristic features. However, recent studies in subjects with borderline hypertension have shown that if the subjects were aware of having hypertension, they showed higher blood pressure and higher reactivity to mental stress and cold-pressor tests than uninformed subjects with similar blood pressures. With respect to regional circulation, studies have shown that the coronary reserve is reduced in early hypertension, and also in subjects without left ventricular hypertrophy. The role of the endothelium in the regulation of blood flow has attracted great interest. Abnormalities in the production of vasoconstricting and vasodilating substances from the endothelial cells may be at least partially responsible for the increased vascular resistance characteristic of essential hypertension. PMID- 7987029 TI - Current work in the cell biology of left ventricular hypertrophy. AB - The capacity of the myocardium to grow depends mainly on the capacity of myocardial cells to synthesize proteins. The capacity for protein synthesis is determined by the quantity of ribosomes present. The rate of ribosome formation is the major factor controlling ribosome content and is limited by the rate of ribosomal DNA transcription. Therefore, hypertensive myocardial growth can be considered as a process of stimulation of gene transcription and protein synthesis in myocardial cells found in animals and humans with elevated blood pressure. Current work in the cell biology of hypertensive left ventricular hypertrophy is directed toward the characterization of the initiating stimuli and the coupling mechanisms that activate the myocardial gene program that, in turn, leads to the acquisition of the left ventricular hypertrophic phenotype. In addition, investigations are being made to define the involvement of changes in myocardial composition and structure in the functional abnormalities of hypertrophied myocardium. PMID- 7987030 TI - A new myocardial conversion of angiotensin I. AB - The therapeutic benefits of angiotensin-converting enzyme inhibitors in the treatment of hypertension, congestive heart failure, and atherosclerotic heart disease are undeniable. Recent studies, however, suggest that the cardioprotective effect produced by these drugs is complex and may not be solely related to inhibition of the generation of angiotensin II. An alternative pathway for the generation of angiotensin II from angiotensin I has been proposed, following the recent identification of a chymotrypsin-like protease (chymase) that may contribute to the formation of angiotensin II in human heart tissue. The enzyme is present in cardiac mast cells and displays unusual substrate specificity for the conversion of angiotensin I to angiotensin II. While biochemical studies have provided convincing evidence for a chymase-dependent production of angiotensin II, the contribution of this enzyme to the physiologic or pathological regulation of arterial pressure and cardiac function remains undetermined. PMID- 7987031 TI - Regression of left ventricular hypertrophy as viewed from the periphery. AB - Despite the advances in antihypertensive therapy, the majority of patients who develop heart failure have antecedent hypertension, left ventricular hypertrophy, and a poor prognosis. Studies in animals and humans have shown that equipotent antihypertensive agents variously effect the regression of cardiac hypertrophy, one of the reasons for which may be the differences in their effects on vascular load and structure. Recent advances in instrumentation (micromanometers, applanation tonometers, ultrasonic probes, and so forth) have permitted the noninvasive measurement of pressure contours, vessel diameters, and pulse-wave velocity. This new technology has allowed the evaluation of the effects of antihypertensive agents on arterial compliance and structure in relation to the agent's ability to regress left ventricular hypertrophy. PMID- 7987032 TI - New developments in the epidemiology of left ventricular hypertrophy. AB - Left ventricular hypertrophy is associated with an increased risk of coronary heart disease and all-cause mortality. Electrocardiographic criteria for left ventricular hypertrophy have high specificity but low sensitivity. Recent advances in methodology have improved the sensitivity of the electrocardiogram for detecting left ventricular hypertrophy. Criteria for left ventricular hypertrophy have been developed from epidemiologic studies using M-mode echocardiography. The prevalence of left ventricular hypertrophy is influenced by blood pressure, age, sex, and obesity. Recent studies have shown that waist-to hip ratio, hyperinsulinemia, a dominant late systolic peak in the arterial pressure waveform, and a decrease in nocturnal blood pressure decline are also determinants of left ventricular mass. Left ventricular hypertrophy is associated with an increased incidence of ventricular arrhythmias and with an impairment in coronary flow reserve. Newer imaging techniques, such as two- and three dimensional echocardiography, magnetic resonance imaging, and ultra-fast computed tomography are more accurate and reproducible than M-mode echocardiography, but these methodologies are expensive and not readily available for assessment of left ventricular mass. PMID- 7987033 TI - Hypertension, myocardial ischemia, and sudden death. AB - Patients with essential hypertension are at an increased risk for sudden cardiac death. As is the case with other complications of hypertension, this increased risk reflects the interplay between a higher prevalence of coronary artery disease and the pathophysiologic consequences of left ventricular hypertrophy. The presence of coronary artery disease is the most important factor, but left ventricular hypertrophy also results in changes in the coronary circulation that predispose to myocardial ischemia, and is also associated with an increased frequency of ventricular arrhythmias. Hypertension itself is associated with changes in the autonomic nervous system that may predispose to sudden death. It is therefore likely that the mechanisms responsible for sudden death are multifactorial, but it is also clear that effective antihypertensive therapy will prevent or mitigate these predisposing factors and will reduce the incidence of this and other cardiac complications. PMID- 7987034 TI - Left ventricular diastolic dysfunction in hypertension. AB - Abnormalities of left ventricular diastolic function in hypertension are multifactorial in origin. Of importance is the demonstration that abnormalities of left ventricular filling in hypertension may be accompanied by deleterious cardiovascular neurodynamic regulations. However, the left ventricular filling rates can be normalized during medical treatment of hypertension. In particular, regression of left ventricular hypertrophy is almost always associated with or followed by improvement of left ventricular filling. The effects of this normalization on cardiovascular dynamics and the outcome of hypertensive heart disease are yet to be demonstrated. PMID- 7987035 TI - Hypertension in the elderly. AB - Hypertension is the most important risk factor for cardiovascular events in the elderly, and it is present in more than 50% of the American population over 60 years of age. Both systolic and diastolic blood pressure are directly related to increasing cardiovascular risk and systolic pressure becomes even more important in the elderly. Borderline isolated systolic hypertension confers an 80% likelihood of developing definite hypertension over 20 years, as well as a higher risk for cardiovascular events. The morbidity trials in the elderly, especially the Systolic Hypertension in the Elderly Program, have clearly demonstrated the benefits of treating hypertension in the elderly in all subgroups examined. Although these benefits have been seen with diuretic (and to a lesser extent beta blocker) regimens, physicians initiated therapy less often with these drugs during 1990 and 1991. All of the major classes of drugs are effective in lowering blood pressure in older whites, and calcium antagonists and diuretics are most effective in older black patients. PMID- 7987036 TI - What can we expect in antihypertensive drug therapy? AB - In the present brief survey on new developments in the drug treatment of essential hypertension, the following issues are summarized: the treatment of hypertension in diabetics, patients with left ventricular hypertrophy, and the elderly; new antihypertensive drugs, including a hybrid (multifactorial) antihypertensive drug with both calcium and alpha 1-adrenoceptor antagonistic activity, as well as angiotensin II-receptor antagonists; and finally, gene therapy in hypertension. PMID- 7987037 TI - Takayasu's arteritis. AB - Takayasu's arteritis is an uncommon condition with a unique constellation of clinical findings that continues to fascinate clinicians and researchers. Advances in the techniques used for classifying lymphocytes, recognizing markers of cellular activity, and detecting the presence of cytokines has produced more evidence that Takayasu's arteritis is a cell-mediated immune condition. The etiology(ies) or triggering mechanism(s) of the disease remains elusive. Alternatives to standard angiography for vascular imaging, such as digital subtraction angiography, duplex ultrasonography, and magnetic resonance imaging, have improved the facility with which the diagnosis and management of Takayasu's arteritis can be safely accomplished. Percutaneous transluminal angioplasty of the aorta and renal arteries is a safe and effective means to dilate symptomatic stenoses. In the short term, this technique provides relief from claudication, hypertension, and ischemia. Long-term follow-up suggests that restenosis at the angioplasty site occurs in a substantial number of patients. Whether this represents a fibrotic healing process or continued inflammation is unclear. Attempts to control the inflammation with anti-inflammatory and immunosuppressive agents continue to be reported. Prednisone plus methotrexate is a promising combination for use in this life-threatening condition of young people. PMID- 7987038 TI - Abdominal aortic aneurysms. AB - The management of abdominal aortic aneurysms has undergone tremendous evolution during the past three decades, resulting in significant advances in our ability to diagnose and safety treat patients with aneurysms. Over the past several years, most research interest has been focused on the etiology of aneurysmal disease, new imaging techniques, cardiac risk stratification, and new approaches for treatment. This article reviews the current approach to diagnosing and treating patients with abdominal aortic aneurysms as well as the results which may be anticipated. In stark contrast to the treatment of nonruptured aortic aneurysms, little progress has been made in the management of ruptured aneurysms, which remain highly lethal. Early identification, prompt evaluation, and surgical repair remain the most important elements in preventing mortality. PMID- 7987039 TI - Penetrating atherosclerotic ulcers of the aorta. AB - The term penetrating atherosclerotic aortic ulcer describes a condition in which an atherosclerotic plaque ulcerates and burrows through the internal elastic lamina into the media, leading to a variable amount of intramural hematoma formation. The typical patient is elderly with multiple cardiac risk factors and presents with acute chest or back pain. Diagnosis of penetrating aortic ulcer may be confirmed by computed tomography, magnetic resonance imaging or aortography. Penetrating aortic ulcers usually occur in the mid- and distal descending thoracic aorta and may be complicated by transmural aortic rupture, embolization, pseudoaneurysm formation, or progressive aneurysmal dilatation. The patient with a penetrating ulcer requires close follow-up to detect the development of complications, and may require surgical therapy. PMID- 7987040 TI - New insights on renovascular hypertension. AB - Although activation of the endocrine renin-angiotensin system with consequent vasoconstriction and salt retention have long been known as the hallmarks of the early phase of renovascular hypertension, the recent recognition of a local vascular angiotensin system and the understanding of the process of vascular remodeling provide new insights into the pathophysiology of this form of hypertension. New pathophysiologic insights as well as technological advances are beginning to alter longstanding clinical approaches to this disease. For example, the captopril renogram has emerged as the screening test of choice in diagnostic evaluation. In addition, new imaging modalities such as magnetic resonance angiography and spiral computed tomography show promise for providing noninvasive anatomical characterization of renovascular disease. Moreover, therapeutic strategies have advanced as a result of better understanding of the natural history of the disease, more effective pharmacologic therapy, and advances in revascularization techniques, such as intravascular stents. This review focuses on these intriguing new developments. PMID- 7987041 TI - Inferior vena caval filters. AB - Interest in the use inferior vena caval filters has grown consistently during the past 8 years, with 51 articles appearing in the medical literature during the past year. The development and introduction of smaller profile devices capable of percutaneous placement has opened the field to interventional radiologists as well as surgeons. The current periodic literature provides a variety of information regarding indications for use, adverse events, experimental models, case reports, long-term clinical studies, and information regarding new devices still in the experimental phase. In caring for patients, it is important to consider carefully the indications for filter placement, the results of long-term performance studies, and the types of complications that can develop from the underlying disorders as well as the devices. Many of the reports are significant in that they provide new, carefully researched information to assist the clinician; some, however, due to poor design or small sample size, merely confuse the issues. PMID- 7987042 TI - Low molecular weight heparins. AB - Low molecular weight heparins are derived from unfractionated heparin by chemical or enzymatic depolymerization; as a result, the mean molecular weight of unfractionated heparin is reduced by about one third and its biochemical and pharmacologic properties are improved. Demonstrated advantages of low molecular weight heparins over unfractionated heparin are the greater bioavailability at low doses, the longer half-life, and the more predictable dose response, which allows for fixed doses to be administered without laboratory monitoring; a potential advantage is the reduced hemorrhagic-to-thrombotic ratio observed in experimental animals. Clinical studies in the prevention of venous thromboembolism have shown that whereas the advantages offered by low molecular weight heparin over unfractionated heparin are modest in general surgery, they are substantial when compared with these and other agents in orthopedic surgery. In addition, low molecular weight heparins are at at least as safe and effective as unfractionated heparin in the treatment of established deep vein thrombosis, but have the advantage that they can be administered once or twice daily without laboratory monitoring and can be used to treat uncomplicated deep venous thrombosis on outpatient basis. PMID- 7987043 TI - Estrogen and the blood vessel wall. AB - This article reviews historical studies and recent advances regarding the direct effects of estrogen on the blood vessel wall. It is organized into two sections that summarize effects of estrogen on vasomotor tone and on vascular cell growth and atherogenesis, based on two recognized actions of estrogen on the vasculature: a rapid vasodilatory effect, and an atheroprotective effect involving inhibition of smooth-muscle cell proliferation. These effects are likely mediated by different mechanisms. The rapid vasodilatory effects of estrogen are probably nongenomic, whereas the antiproliferative effects of estrogen are likely due to estrogen receptor-dependent alterations in gene expression. Overlap between these two mechanisms also exists, in that genes regulating the production of two important vasodilators synthesized by the vessel wall (prostacyclin and nitric oxide) can be up-regulated by estrogen. Potential molecular mechanisms by which estrogen exerts its effects are discussed, and future directions in this rapidly evolving area of research are considered. PMID- 7987044 TI - Intravascular ultrasound imaging in peripheral arterial and coronary artery disease. AB - Intravascular ultrasound is an emerging imaging modality that employs miniaturized transducers at the tips of catheters to provide detailed information about the morphology of small and large arteries. While there is ongoing development in technology, currently available intravascular ultrasound instrumentation already augments angiography in the assessment of structural and dynamic abnormalities of the peripheral and coronary arterial systems. Recent studies have consistently demonstrated significant underestimation of atherosclerotic disease by angiography. Demonstration by intravascular ultrasound of disease in the angiographically normal "reference" segment and of remodeling of the diseased segment may explain this angiographic underestimation. Intravascular ultrasound also has many applications during various catheter-based therapeutic procedures. In addition to contributing to our understanding of the mechanisms of interventions and restenosis, intravascular ultrasound may lead to better guidance and ultimately better outcome during various procedures such as balloon angioplasty, atherectomy, and stent placement. PMID- 7987046 TI - Transcriptional regulation of the dihydrofolate reductase/rep-3 locus. AB - This review summarizes many studies that have used the mouse, hamster, or human dihydrofolate reductase locus as a model system for the study of basal or regulated transcription. This locus encodes two genes, dhfr and rep-3, that are oriented in opposite directions. The dhfr promoter and the two rep-3 promoters are highly GC-rich and do not contain consensus TATA boxes. The cis-acting elements important in basal transcription of these non-TATA box promoters have been mapped, revealing that Sp1 plays a dominant role, and that sequence elements both upstream and downstream of the initiation site contribute to transcriptional activity. Future studies will be directed toward understanding the assembly of transcription complexes on these promoters. The expression of the dhfr gene following treatment of cells with many different stimuli has been analyzed, and in many, but not all, cases the response has been at the transcriptional level. In those systems where the regulatory cis-acting element has been mapped, the E2F sites flanking the transcription initiation site play a central role in mediating the response. Future studies will be directed at characterizing the regulatory protein E2F and understanding how it interacts with the basal transcription complex at the dhfr promoter. The rep-3 gene contains two promoters that are both growth responsive: one promoter is regulated by E2F, the regulator of the other promoter has not been identified. In summary, the in-depth characterization of the 1 kb containing the dhfr and rep-3 promoters has begun to provide a detailed understanding of growth-responsive transcription. PMID- 7987045 TI - The glucose-regulated proteins (GRP78 and GRP94): functions, gene regulation, and applications. AB - The knowledge of GRPs as molecular chaperones is rapidly evolving. It is anticipated that the GRPs will make special contributions in the areas of basic cell biology, biotechnology, and cancer biology. In particular, they may play a role as the prototype of a class of genes that are regulated by signal transduction pathways originating in the ER and traveling to the nucleus. GRP78 and GRP94 function as molecular chaperones and can bind to malfolded proteins and unassembled complexes. They are induced in response to stress, but once the stress is removed the GRPs are posttranscriptionally modified into biologically inactive forms. The promoters of the grp genes are highly conserved, with several CCAAT-like motifs and GC-rich regions. The high level of redundancy that exists in the mammalian grp promoters may act to ensure that the expression of the genes, both of which are single copy, is unlikely to be significantly lowered in the event of mutation. These genes are thought to be controlled by several transcription factors whose complex interactions with the grp promoters allow variable patterns of grp induction. The promoters of the grp genes constitutively express their gene products, and their promoter activities can be further enhanced in cellular environments of low glucose or oxygen. The grp78 promoter is known to retain its strong activity in differentiated and undifferentiated tissues. These features make it an attractive alternative to viral promoters for use in gene therapy. Gene therapy may also be useful in treating cancer in some cases, especially solid tumors. In these instances, GRP levels are already likely to be quite high. These high levels of GRPs may inhibit the efficacy of several anti-cancer treatments. Suppression of GRP induction, perhaps by anti-sense or ribozyme technology, may prove to be useful in conjunction with anti-cancer drugs to treat tumors. PMID- 7987048 TI - Renaissance considerations on the nature of the tongue. PMID- 7987049 TI - The development of the dental profession in Sweden. PMID- 7987047 TI - Steroid hormone-induced expression of oncogene encoded nuclear proteins. AB - In this article we have attempted to review the literature on the regulation of nuclear protooncogene expression by steroid hormones and other small molecules that interact with receptors of the steroid/thyroid superfamily. Until about 5 years ago, there were relatively few reports of steroidal regulation of cellular oncogenes, but hundreds of papers on this topic have appeared since then. This demonstrates the intense interest in this area that has developed recently. It now been demonstrated that all the major classes of steroid hormones control expression of nuclear protooncogenes in one or more systems. Given the actions of these proteins as transcription factors and their central role in cellular communications systems, it seems likely that they play a key role in mediating the biological effects of steroids on processes such as proliferation and differentiation. To date, most of the work in this general area has focused primarily on the regulation of three genes: c-fos, c-jun, and c-myc. However, a quick glance at the table of nuclear protooncogenes in the introduction of this article indicates that over 40 nuclear protooncogenes are now recognized. For the large majority of these, regulatory effects of steroids and related molecules have not yet been reported. Hence, we predict that reports in this general area of research will continue to appear at a very rapid rate over the next few years. In addition, we have tried to provide enough background information for readers to get an overview of the regulation of nuclear protooncogene expression by nonsteroidal factors. We felt this information was important to emphasize that steroid hormones represent only one of the many classes of regulatory molecules that control expression of nuclear protooncogenes. Thus, an important area for future research will be to understand how these multiple regulatory systems interact to control expression of this important class of cellular oncogenes and the biological processes that they mediate. PMID- 7987050 TI - Dentistry on stamps. The stamp that did not make it. Horace Wells. PMID- 7987051 TI - Prosthetics, periodontal therapy and conservative dentistry in the eighteenth century: archeological findings from Grand Sacconex, Geneva, Switzerland. AB - There are only few archaeological findings on therapeutic measures dating to the early times of scientific dentistry. The remains of two burials from the mid eighteenth century permit the assessment of the spectrum of dental treatments of that time. Bridges, ivory dentures, gold ligatures for splinting as well as various metal fillings demonstrate the state-of-the-art of contemporary practical dentistry. A presentation of the findings should be of interest not only for the history of dentistry but can also supplement the written records of that time. PMID- 7987052 TI - Paul Sheppard Burnham, DDS (1903-1987). AB - A search via databases and indexes, as well as the American Dental Association package library collection, yielded no evidence of participation by American dentists in outboard motor or hydroplane inboard motor boat racing. There may be or have been such participants, but the contributions of Paul Sheppard Burnham, DDS are noteworthy and quite probably unique. Competing always as an amateur, his racing ability was respected; on many occasions he outraced professional drivers. Dr. Burnham led an interesting life. In his 83 years, he operated and soon thereafter traded automobile after automobile (a total of 49)--satisfying his love for fast and unusual cars. While practicing dentistry most of his adult life, he managed to become an integral part of the Rehoboth Beach, DE beach patrol, serving for ten years as captain of lifeguards and, in a few of his senior years, as chief. As the 20th century comes to a close, a good deal is written and spoken about those identified as unusual, vibrant, daring, spirited, competitive, self-confident, and colorful--travelers in the fast lane. Paul S. Burnham, DDS spent a great part of his life in the fast lane, with very few in front of him. PMID- 7987053 TI - Gleanings about dentistry from the world of literature. PMID- 7987054 TI - The excavator. PMID- 7987055 TI - U.S. Army Military History Institute. PMID- 7987056 TI - [Diagnostic imaging in acute pancreatitis]. AB - With a sensitivity of 90% in the diagnosis of necrotic pancreatic tissue contrast enhanced computed tomography is the most reliable imaging tool for classifying acute pancreatitis. ERCP is essential for the diagnosis of stones in the common bile duct and in the pancreatic ducts and of tumors of the duodenal papilla and the pancreatic head and thus for clarifying the etiology of acute pancreatitis. Sonography as the only imaging tool would not be sufficient, because its sensitivity for necrotizing pancreatitis is only 33% and stones in the common bile duct are often missed. PMID- 7987057 TI - [MR tomography of acute pancreatitis: initial results]. AB - Magnetic resonance imaging (MRI) was evaluated for its potential in assessment of acute pancreatitis compared to computed tomography (CT). 15 patients with acute pancreatitis were examined using a routine protocol including T1- and T2-weighted sequences and a fat-suppressed T1-weighted spin-echo sequence. Gadopentant Dimeglumin (Gd-DTPA) was given. For comparison, plain and contrast-enhanced CT was performed prior to MRI. MRI proved to be superior to CT in detection of bleeding, duodenitis and ascites. MRI failed to detect concrements. These first results show that, considering the latest development in technology, MRI is not inferior to CT in diagnostic imaging of acute pancreatitis. PMID- 7987058 TI - The Budd-Chiari syndrome: clinical presentation and diagnostic findings in 45 patients treated by surgery. AB - We report on the clinical presentation and diagnostic findings in 45 patients with Budd-Chiari syndrome. The diagnosis was confirmed by histology at the time of liver transplantation (n = 37) or shunt surgery (n = 8). An underlying disorder could be established only in half of the patients, oral contraceptives as predisposing factor were known in 18 cases. Clinically, abdominal pain and distension as well as hepatomegaly and ascites were most frequent findings, whereas changes in laboratory data were more or less unspecific. By use of repeated ultrasound, a definite diagnosis of a Budd-Chiari syndrome could be confirmed in all cases by obligatory demonstration of obstruction or thrombosis of at least one major liver vein. Hepatic venography revealed only one false negative result. Celio-mesenteric arteriography plus portography, cavography and preoperative liver biopsy did not present additional diagnostic information. These techniques may contribute to treatment planning of portosystemic shunt surgery or hepatic transplantation. In conclusion, the presence of hepatosplenomegaly, ascites, abdominal pain and distension, especially in combination with a known hypercoagulable state, should alert to the possibility of a Budd-Chiari syndrome. Ultrasound is the diagnostic tool of choice. Hepatic venography should only be performed if even repeated ultrasound is not conclusive. PMID- 7987059 TI - [Ultrasound controlled extracorporeal shockwave lithotripsy of pancreatic calculi in patients with chronic recurrent pancreatitis]. AB - A consecutive series of 10 patients with pancreatic stones due to chronic pancreatitis was treated by extracorporeal shockwave lithotripsy during an investigation period of 2 years. The first step of the therapeutic regime included an endoscopic sphincterotomy prior to shockwave treatment. The targeting procedure was performed strictly under sonographic control. All patients were treated with a second-generation electrohydraulic lithotriptor, fragmentation could be achieved in all 10 cases. In 7 patients stonefreeness could be reached by endoscopic stone extraction, all these patients were symptom-free over a follow-up period of 12 months. In 3 patients complete duct clearance could not be achieved, these patients presented with minor symptoms over the follow-up period. PMID- 7987060 TI - [Comparison of CT and MRI in diagnosis of tumors of the nasopharynx, the inner nose and the paranasal sinuses]. AB - A total of 292 patients with tumors of the nasopharynx, the nose and the paranasal sinuses--264 cases with malignant tumors--were examined with magnetic resonance imaging (MRI) and computed tomography (CT) for comparison. MRI yielded better results than CT in the detection and staging of neoplasms of the nasopharynx (detection: CT 84.9%, MRI 96.7%; staging: CT 75.2%, MRI 92.4%). The walls and septae of the paranasal sinuses and of the skull base were in all cases best visualized on high-resolution CT with thin slices. Tumor detection, differentiation of tumor and inflammatory tissue and staging, however, were better achieved using MRI than CT (detection: CT 84.7%, MRI 91.6%; staging: CT 78.6%, MRI 80.9%). The use of fast and ultrafast MR sequences (alternatively or additionally to 'conventional' spin echo sequences) improved the tumor diagnosis. We therefore recommend that patients with tumors of the nasopharynx, the nose and the paranasal sinuses undergo MRI with fast spin echo and gradient echo sequences as first imaging modality. PMID- 7987061 TI - [Initial experiences with ultrasound angiography in the area of extracranial and peripheral arteries]. AB - First experience with ultrasound angiography of extracranial and peripheral arteries in 20 patients is reported. Ultrasound angiography is a new method of color-coded vessel imaging. It is based on signal processing of the blood flow amplitudes. Color imaging of echo signals by ultrasound angiography is independent of the direction and velocity of blood flow and of the angle of ultrasound beam. Aliasing and changes of colors due to changes of direction do not exist. We found a sharper imaging of the vessel lumen and the vessel wall compared with color Doppler. Imaging of vessel branches and small vessels is even better. Documentation of vessels by ultrasound angiography is similar to angiography and can be obtained convincingly. Application of this method in addition to color-coded duplex sonography is recommended. PMID- 7987062 TI - [Teleradiology with personal computers]. AB - A system to transmit radiographic images with the aid of a personal computer (PC) via phone line is presented. The pictures are recorded by a camcorder and digitized by the PC. They are sent to the receiver by a modem via phone line. The different steps can be programmed. MR and CT pictures as well as ordinary x-ray pictures have been transmitted. It takes about 45 s to send a picture. It arrives in good quality, and findings are clearly represented. After the sending process is completed, all pictures can be reviewed in seconds. The presented system is interesting for its low price when a PC is available. PMID- 7987063 TI - Rhodococcus equi pneumonia in an HIV-infected patient. AB - We report a case of a 46-year-old HIV-infected patient suffering Rhodococcus equi pneumonia and septicaemia. After the failure of an initial antibiotic treatment, the upper lobe of the right lung was resected due to a cavitating pneumonia. After that the patient stabilized for a period of 7 months by administration of a resistogram-adapted combination of tetracycline, erythromycin and clindamycin. Due to the patient's decision, antibiotic treatment was stopped when a cytomegalovirus retinitis was diagnosed. Six weeks later new pulmonary infiltrations were diagnosed and a Rhodococcus equi bacteraemia evolved. The patient died one year after the first diagnosis of the Rhodococcus equi infection. The present case suggests that the infection with Rhodococcus equi in patients with advanced HIV infection demands permanent antibiotic prophylaxis. PMID- 7987064 TI - Blunt trauma of the spleen: the delayed rupture in computed tomography. AB - We retrospectively reviewed CT scans of 18 patients (12 males and 6 females; mean age: 43.6 years) with the diagnosis of blunt splenic trauma. All patients underwent CT at different times after the trauma. The cases were divided into 2 groups: according to the time at which the CT was performed, the 1st group consisted of 11 patients scanned within 48 h after the trauma; the 2nd group consisted of 7 patients studied with CT at variable times after the traumatic event (mean time: 6.5 days; range 3-13 days). All lesions in the 1st group (11 patients) had indistinct margins, while lesions of patients in the 2nd group (7 patients) always showed clean-cut and regular edges. Early lesions were always hyperdense, late ones hypodense. CT diagnosis always matched the surgeon's diagnosis. We can confirm the diagnostic value of CT of splenic lesions in blunt abdominal traumas. PMID- 7987066 TI - Proliferating cell nuclear antigen expression in Wistar rat livers. A retrospective immunohistochemical study of normal and neoplastic livers. AB - Formalin-fixed, paraffin-embedded liver specimens from 27 2-year-old Wistar rats, including 10 normal livers, 11 hepatocellular adenomas, 2 hepatocellular carcinomas, and 4 cystic cholangiomas, were immunostained using the streptavidin/peroxidase method and the PC10 monoclonal antibody (Mab), which recognizes an epitope on the proliferating cell nuclear antigen (PCNA). The following PCNA labeling index (LI) mean values were found for the above four groups of liver specimens: normal livers, 0.43 +/- 0.31%; hepatocellular adenomas, 1.51 +/- 0.59%; hepatocellular carcinomas, 24.80% +/- 10.28%; and cystic cholangiomas, 0.61 +/- 0.21%. Our findings indicate that PCNA LI clearly separates liver malignancies from other benign liver tumors, as well as from normal, non-neoplastic, liver tissues. Although the mean PCNA LI values seemed to reflect histological grading (i. e. normal, neoplastic benign, neoplastic malignant), overlapping between normal livers and hepatocellular adenomas was observed in five cases (i. e. in 2 normal livers and 3 hepatocellular adenomas, where the PCNA LI values varied between 0.74% and 0.96%). It thus appears that PCNA immunohistochemistry represents a promising tool for investigating liver cell proliferation in laboratory rats, and permits distinguishing between benign and malignant liver parenchymal tumors. PMID- 7987065 TI - Failure of protection against endotoxin hepatotoxicity by selenium. AB - The present study was undertaken in rats to test the ability of selenium to prevent endotoxin hepatotoxicity. There were no significant morphological changes in the liver and no abnormalities of liver function in rats given 0, 6.25 or 12.5 mumol of selenium. Endotoxin administration to these rats induced focal hepatocellular coagulative necrosis and increased serum transaminase activities. However, endotoxin hepatotoxicity and mortality of the rats given endotoxin after treatment with 6.25 or 12.5 mumol of selenium were not significantly lower than in those given endotoxin alone. These facts suggest that selenium does not prevent endotoxin hepatotoxicity. PMID- 7987067 TI - Characterization of historical samples of nickel refinery dusts from the Clydach refinery. PMID- 7987068 TI - Effects of novobiocin on the induction of gamma-glutamyltranspeptidase positive foci in the liver of rats treated with diethylnitrosamine. AB - Effects of novobiocin on the induction of gamma-glutamyltranspeptidase(GGT) positive foci, an early lesion occurring during hepatocarcinogenesis, after diethylnitrosamine(DEN) initiation were investigated in Fischer 344 rats. Animals were given DEN at a dose of 20 mg/kg b. w. followed by novobiocin at doses of 50, 100 and 200 mg/kg b. w. The latter two doses, but not 50 mg/kg b. w., significantly inhibited the development of GGT-positive foci, providing evidence of the possible involvement of mono(ADP-ribosyl)ation in the initiation phase of hepatocarcinogenesis in rats. PMID- 7987069 TI - Functional and morphological characterization of neuropathy induced with 5 lipoxygenase inhibitor CGS 21595. AB - Peripheral toxic neuropathy induced in rats with a 5-lipoxygenase inhibitor CGS 21,595 was characterized using special functional tests and pathological procedures. Functional tests included measurement of grip strength, landing foot splay, assessment of sensorimotor and autonomic functions and monitoring of motor activity. Pathological procedures consisted of perfusion fixation, embedding in plastic, teasing of isolated nerve fibers, and light and electron microscopy. Male and female albino rats received the test article orally by gavage on 5 days per week. To characterize the development of the lesion animals treated with 1000 mg/kg were examined and sacrificed at 2-week intervals until termination at 10 weeks. In a separate study, the dose-effect relationship was examined in groups of animals treated with 50,200 or 1000 mg/kg for 10 weeks. Neurotoxicity occurred only in animals treated with 1000 mg/kg and was first detected following 4 weeks of treatment. Although there were no overt clinical signs of neurotoxicity, functional examination detected a reduction of grip strength, increased landing foot splay and reduced motor activity. Neuropathological examination revealed peripheral segmental demyelination affecting predominantly the Schwann cells in the ventral spinal nerve roots. Owing to its unusual localization in the nervous system and to subtlety of functional signs, peripheral segmental demyelination represents a special diagnostic challenge in toxicological safety studies. PMID- 7987070 TI - Peroxisome proliferation of hepatocytes in rats by a microbial degradation product of cholic acid, 4-(decahydro-6-methyl-3-oxocyclopenta(f)quinoline-7 yl)valeric acid. AB - Three-week oral administration of 4-(decahydro-6-methyl-3-oxo cyclopenta(f)quinoline-7-yl)valeric acid (32-1328) in the diet supplemented at concentrations of 0.1% or 0.3% was associated with hepatomegaly and hypotriglyceridemia in male F344 rats. Electron microscopic examination of the liver revealed a remarkable increase of peroxisomes in hepatocytes both in number and size. Biochemically, there were increased activities of peroxisomal marker enzymes including the heat-labile enoyl-CoA hydratase and catalase while the mitochondrial enoyl-CoA hydratase activity was unchanged after feeding of 32 1328. These findings indicate that 32-1328 can exert peroxisome-proliferating activity to rat liver in a manner similar to typical peroxisome proliferators such as clofibrate or di(2-ethylhexyl)phthalate. PMID- 7987071 TI - Fatty acid composition in liver, serum and brain of rat inhalated with trichloroethylene. AB - Temporal variations in chronic effects of inhalated 300 ppm trichloroethylene (TCE) on the fatty acid composition in rats were investigated to clarify influences of TCE on the fatty acid metabolism of serum, liver and brain, including synaptosome, myelin and mitochondria fractions on weeks 0, 4, 8, 12 after exposure and on week 4 after rehabilitation started following 12 weeks exposure. On week 4, rats exposed to TCE had significantly lighter body weight, lighter epididymal fat pads weight and heavier liver weight compared with controls. In liver and serum, increases in 16:0, 18:0, 18:1n-9, 20:2n-6, 20:3n-6 and 20:4n-6 and decreases in 18:2n-6, 18:3n-6, 18:3n-3, 20:5n-3, 22:5n-3 and 22:6n-3 were also observed. The differences between the exposure and the control groups in the fatty acid composition in liver and serum, except for 18:1n-9 and 18:2n-6, did not enhance from week 4 after TCE exposure. In brain, significant changes of fatty acid composition caused by TCE appeared as decreases in 18:2n-6 and 22:5n-3, and increases in 20:4n-6 and 22:4n-6 during the whole exposure period. Changes of fatty acid composition in brain occurred in the same manner as in serum and liver phospholipids, except that 18:1n-9 was elevated in mitochondria. Changes in brain were slighter and appeared later than those in liver and serum. TCE had a strong effect on the fatty acid composition of mitochondria in neural cells.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7987073 TI - A new reliable method of culturing and measuring human decidual capillary endothelial cells. AB - A reliable method of culturing human decidual capillary endothelial cells was developed. Endothelial growth cell supplement, heparin and newborn bovine serum were added to the culture medium to facilitate growth. Decidual capillary endothelial cell cultures showed similar growth curves to the more traditional human umbilical cord vein endothelial cell cultures. Culture growth was assessed by a new morphometric method of measuring cell culture area with the use of a computerised measuring tablet. This new method was compared with the more laborious method of counting individual cells and was found to be as reliable and more efficient. PMID- 7987072 TI - Glutathione status, lipid peroxidation and kidney function in streptozotocin diabetic rats. AB - In adult female rats diabetic nephropathy was induced by i.v. administration of streptozotocin (6 mg/100 g b.w.). The animals survive for 3 weeks when very low daily doses of insulin (0.3 IU/animal) are administered. High blood urea concentrations and distinct proteinuria indicate the impairment of kidney function in streptozotocin diabetic rats. Streptozotocin induces mild polyuria and increased renal excretion of potassium; there is also an increase in renal excretion of administered p-aminohippurate. Three weeks after administration of streptozotocin the formation of lipid peroxides is increased in the kidney. At this time glutathione content (GSH, GSSG) is unchanged in liver and kidney of streptozotocin diabetic rats. Impairment of kidney function in streptozotocin diabetic rats can be prevented by daily supplementation with sufficient doses of insulin (about 3 IU/animal). PMID- 7987074 TI - Rarely occurring spontaneous metastasizing testicular tumors in rats. Histopathologic and ultrastructural features. AB - Testicular tumors are not uncommon in aging rats. However, metastasis from these neoplasms to several distant visceral organs has not been reported. Testicular tumors were observed in a total of 18 (1.34%) Sprague-Dawley rats out of 1340 males examined. Out of these 18 neoplasms, interstitial tumors were observed in 12 rats, of which 11 were benign and one malignant. Spermatic seminomas were observed in two (0.15%) cases (one benign and one malignant). Both rats with malignant testicular neoplasms were sacrified in extremis. Remaining four tumors were classified as mesotheliomas. Detailed gross, histopathologic and electron microscopic features of primary testicular neoplasms with metastases to several distant visceral organs are described and discussed. PMID- 7987075 TI - Chronic alcohol intake and carbachol-induced acute pancreatitis in the rat. AB - Alcohol-induced changes in cholinergic and pancreozymin pathways regulating exocrine pancreatic secretion have been proposed to play a crucial role in the pathogenesis of acute alcoholic pancreatitis. In the present study we investigated the role of chronic alcohol intake in an experimental acute pancreatitis induced in rats by cholinergic hyperstimulation. Chronic alcohol intake interfered with the function of rat pancreatic muscarinic receptors in carbachol-induced acute pancreatitis. However, chronic alcohol intake did not sensitize the experimental animals to cholinergic hyperstimulation. Whether this increased resistance at the level of pancreatic muscarinic receptors contributes to acute alcoholic pancreatitis is discussed in the present article. PMID- 7987076 TI - Changes by progesterone derivatives in fatty acids from phosphatidylcholine and phosphatidylethanolamine fractions in rat liver endoplasmic reticulum. AB - The effects of two progesterone metabolites on fatty acid composition of phosphatidylcholine (PC) and phosphatidylethanolamine (PE) from total liver and liver microsomes were studied in female rats. 16 alpha-Hydroxyprogesterone significantly increased the amount of fatty acids esterified to PC and PE fractions in total liver and liver microsomes. Both saturated and unsaturated fatty acyl components were enhanced. In contrast, 5 beta-pregnan-3 alpha-ol-20 one caused a reduction of fatty acids bound to PC and PE fractions from total liver and liver microsomes. Pregnanolone decreased both saturated and unsaturated fatty acids. Changes in specific fatty acids occurred in palmitic and stearic acids among saturated components, and palmitoleic, oleic, linoleic, eicosatrienoic, arachidonic and docosahexenoic acids among unsaturated ones. The unsaturated: saturated fatty acid ratio was raised by 16-alpha hydroxyprogesterone and lowered by 5 beta-pregnan-3 alpha-ol-20-one in all phospholipid fractions. The induction of drug metabolizing enzymes by 16 alpha hydroxyprogesterone may be related to an enhanced synthesis of microsomal phospholipids containing unsaturated fatty acids, particularly arachidonic and docosahexenoic acids. In contrast, the inhibition of drug metabolism by 5 beta pregnan-3 alpha-ol-20-one is associated with reduced formation of unsaturated fatty acyl side chains. PMID- 7987077 TI - Stromal collapse in acute atrophy of lymphoid organs. AB - The formation of post-collapse fibrosis was investigated in lymphoid tissues of rats simultaneously treated with cyclophosphamide and betamethazone. Effectiveness of treatment was monitored by means of peripheral blood smears. Animals were sacrificed 1, 2, 3, 4, and 7 days after the last injection. Fragments of lymph nodes and thymus were studied by light and electron microscopy. Compared with untreated controls, lymphoid organs from treated animals revealed considerable reduction in the number of cells and condensation of the stroma. Picrosirius-red stained slides seen under polarized light revealed the condensed stroma to contain mainly collagens. Electron microscopy confirmed the presence of collapsed collagen fibrils in the absence of signs of functional activation of the connective tissue cells within the collapsed areas. This investigation shows that a pure form of collapse fibrosis can be observed in lymph nodes and thymus following sudden atrophy of lymphoid cells. PMID- 7987078 TI - Quantification of hepatocytic proliferation in the laboratory mouse. A comparative study using immunohistochemical detection of bromodeoxyuridine (BrdU) incorporation and proliferating cell nuclear antigen (PCNA) expression. AB - The proliferation rate in livers of 120 mice (60 males and 60 females) was analyzed by immunohistochemical detection of bromodeoxyuridine (BrdU) incorporation and proliferating cell nuclear antigen (PCNA) expression on ethanol fixed/paraffin-embedded specimens. Mice were divided into three groups, with 20 males and 20 females in each group: mice in the first group served as controls, while mice in the second and third groups were treated with a low and a high dose, respectively, of a non-genotoxic drug candidate for 2 weeks. A dose-related increase of the proliferating hepatocyte fraction was disclosed by both immunohistochemical methods, reaching statistical significance already in the low dose male group for BrdU incorporation and in both male and female low-dose groups for PCNA expression. A good correlation between the degree of BrdU and PCNA labeling was observed and, as expected, the percentage of PCNA expressing cells was generally higher than the percentage of BrdU-positive cells. We concluded that the detection of PCNA expression represents a reliable method for the quantification of the hepatocytic proliferating fraction in rodents and allows the use of archival material for cell kinetic investigations in toxicologic pathology. PMID- 7987079 TI - [The health status of our population has reached a high status]. PMID- 7987080 TI - [Quality management between science and competition]. AB - The call for an increase in quality assurance becomes louder and louder. However, it is almost always understood as a more intensive monitoring of quality. The ideas of total quality management described in the ISO norms 9000-9004 gain ground only slowly. By defining quality indicators and developing practical guidelines or appropriate methods of quality management, science could provide the basis. Information processing can make essential contributions such as the profiles of the German perinatal surveys or the Swiss gynecological-obstetrical quality statistics developed by Hochuli et al., but the only way to a widely applied total quality management is quality-assuring activities and quality becoming factors of competition themselves. PMID- 7987081 TI - [Ultrasound measurements of the diameter of the aorta and pulmonary trunk of the fetus]. AB - Fetal cardiac measurements derived in the five-chamber and the short-axis view were performed in uncomplicated pregnancies between the 20th and the 40th week of gestation. Using cine loop and zoom techniques, the diameters of the aortic and pulmonary valve were measured (n = 157) and the pulmonary trunk/aorta ratio calculated. Normal ranges for both parameters were constructed and correlated with gestational age. Both diameters showed a linear increase during gestation (aorta r = 0.87, pulmonary trunk r = 0.91). The mean pulmonary trunk/aorta ratio had a constant value of 1.25 and showed no changes throughout pregnancy. In 128 fetuses the heart width was further measured and the vessel diameters were presented in correlation to the heart width. PMID- 7987082 TI - [Results of 35 ambulatory gamete transfers: evaluation of a successful method using regional anesthesia]. AB - Thirty-five ambulatory gamete transfers were performed in 29 patients, resulting in a pregnancy rate of 40% and a take-home baby rate of 26%. Upon request 10 transfers in 9 patients were done under epidural anesthesia. The avoidance of general anesthesia allows the patient to consciously participate in her treatment and improves postoperative recovery. Our results suggest that gamete transfer procedures can be carried out under epidural anesthesia with no adverse effects on the pregnancy rate. PMID- 7987083 TI - [Determination of kidney function in patients with ovarian cancer treated with chemotherapy: calculation versus measurement of creatine clearance]. AB - In patients with ovarian cancer receiving chemotherapy we compared the creatinine clearance measured in the usual way with the calculation of the creatinine clearance according to the formulas of Jelliffe and Cockroft. Regression analysis only showed a moderate correlation, whereas the analysis of the data by ROC curves allows the use of these formulas as screening tests with acceptable values of sensitivity and false-positive rate. Therefore, in the majority of these patients, collecting urine over 24 h before starting chemotherapy is no longer necessary. PMID- 7987084 TI - [Knife conization versus loop excision--clinical and histomorphologic results]. AB - Ninety patients with cervical intraepithelial neoplasia (CIN) were randomly assigned to loop excision (n = 38) or cold-knife conization (n = 52). All specimens were well evaluable at histology. Compared with cold-knife conization, loop excision removes less healthy tissue without reducing the chances for cure. PMID- 7987085 TI - [Interaction of interferon with retinoic acid]. AB - Lippman and coworkers recently reported striking response rates achieved in patients with cervical cancer using a combined treatment with 13-cis-retinoic acid and interferon-alpha. In vitro studies demonstrated a synergistic amplification of proliferation inhibition by retinoids and interferon in malignant cells. Comparing all-trans- with 9-cis-retinoic acid, the latter was more effective in inhibiting tumor cell growth and in inducing synergism with interferon-gamma. Combination of retinoic acid with interferon-gamma increased the down-regulation of specific binding sites of interferon-gamma. Expression of MHC class II antigens induced by interferon-gamma was not further enhanced by retinoic acid. These results indicate that interferon seems to modulate the retinoic acid system. PMID- 7987086 TI - [Asymptomatic varicella infections in pregnancy: detection and problems]. AB - Two cases of asymptomatic varicella infection during pregnancy will be presented. The diagnosis was made by the evidence of varicella-zoster-virus (VZV)-specific IgM or by the significant increase in antibody titer. The incidence of such subclinical VZV infections must be the issue of further investigations. Because of the rare occurrence of an embryopathy no general screening is usually made. On the other hand serological testing is recommended in cases of VZV infection in the surroundings of a pregnant woman. The problem of false-positive enzyme immunoassays make it necessary to confirm the results with one, or better two, additional methods. PMID- 7987087 TI - [A pioneer in surgical gynecology. On the 55th anniversary of the death of Paul Ferdinand Strassmann (23 October 1866 to 15 August 1938)]. AB - This year (1993) we want to commemorate the 55th anniversary of the death of the Berlin gynecologist Prof. Paul Ferdinand Strassmann. In the first half of the 20th century, Strassmann was one of the leading specialists of plastic surgery of the female genital tract. Famous gynecologists and surgeons, e.g. the Mayo brothers, visited the Strassmann clinic in the Schumannstrasse with the aim of learn new surgical techniques. The present paper aims to outline particularly the life of Paul F. Strassmann but also his importance in the creation of modern gynecological surgery. PMID- 7987088 TI - ["Joint Meeting of the RCOG and ECOG" on the topic "Training in Obstetrics and Gynecology in Europe" December 1993]. PMID- 7987089 TI - [Training in Obstetrics and Gynecology in Europe". Joint Meeting of the ECOG and RCOG, London, 10th and 11th December 1993]. PMID- 7987090 TI - [Zidovudine in prevention of HIV transmission by the infected mother to her child]. AB - The effectiveness of a zidovudine prophylaxis to decrease vertical HIV transmission was tested in a multi-centre (59 clinics in the USA and France), randomised, placebo-controlled study. The mother was given zidovudine orally from the 14th gestational week and intravenously during delivery. The child was treated orally for the first 6 weeks of life. This prophylactic treatment resulted in a significant reduction of vertical HIV transmission from 26 to 8%. Although there are still some open questions, especially concerning the long-term consequences for the child, the Swiss Associations of Gynaecology and Obstetrics and of Paediatrics recommend using zidovudine for prophylaxis in the routine care of HIV-infected pregnant women. PMID- 7987091 TI - [Current discussion regarding drug package inserts for hormone preparations]. PMID- 7987092 TI - [Ultrasound in Fetal Medicine II. St. Ulrich in Groden, 30 January to 4 February 1994]. PMID- 7987093 TI - The future of medicine. PMID- 7987094 TI - Divided we fall (yet again) PMID- 7987095 TI - Dietary protein and progression of chronic renal disease. PMID- 7987096 TI - The new measles campaign. PMID- 7987097 TI - The eradication of gonorrhoea. PMID- 7987098 TI - Commission calls for shake up in welfare state. PMID- 7987099 TI - Australia rules that doctors own their notes. PMID- 7987100 TI - Measles campaign is mismanaged, claim GPs. PMID- 7987101 TI - Blood is a European issue. PMID- 7987102 TI - Population need for renal replacement therapy in Thames regions: ethnic dimension. AB - OBJECTIVES: To determine the use of renal replacement therapy by ethnic origin and to ascertain the variation in provision of such therapy and to relate this to the distribution of ethnic minority populations. DESIGN: Analysis of retrospective and cross sectional data from 19 renal units. SETTING: All four Thames regional health authorities. SUBJECTS: Patients resident in the Thames regions who were accepted as new patients for renal replacement therapy during 1991 and 1992 and the patients who were already undergoing such treatment between December 1992 and April 1993. MAIN OUTCOME MEASURES: Rates of acceptance for and prevalence of renal replacement therapy among white, black, and Asian people. RESULTS: The average annual acceptance rates per million in 1991-2 were 61 for white people, 175 for black people, and 178 for Asians, and the prevalences per million were 351, 918, and 957 respectively. The relative risks increased with age. A threefold increase in the acceptance rate occurred in people aged under 55 in both the black and Asian populations, suggesting that the higher rates are probably not due to factors related to access alone. Treatment rates varied considerably among districts, reflecting both the distribution of ethnic minority populations and access to services. CONCLUSION: Black and Asian people receive and have a greater need for renal replacement therapy, and the need will increase as these populations age. These findings have important implications for the provision of renal services in districts with a high proportion of ethnic minorities and for the management of diabetes mellitus and hypertension, two important causes of end stage renal failure in these populations. PMID- 7987103 TI - Helicobacter pylori infection in childhood: risk factors and effect on growth. AB - OBJECTIVE: To investigate the current prevalence of Helicobacter pylori infection in childhood, the risk factors for infection, and the effect of infection on growth in preadolescent schoolchildren. DESIGN: Population based sample of 7 year old schoolchildren followed up at age 11; data on risk factors for infection collected at age 7; presence of infection at age 11 determined by measurement of salivary IgG against H pylori by a newly developed enzyme linked immunosorbent assay (ELISA). Height was measured at 7 and 11 years of age. SUBJECTS: 554 schoolchildren from Edinburgh. RESULTS: 62 (11%) children had H pylori infection. Independent risk factors for infection were single parent families (adjusted odds ratio = 2.5; 95% confidence interval 1.1 to 5.7), the 10% most crowded homes (3.1; 1.3 to 7.2), and schools serving predominantly rented housing estates (2.5; 1.0 to 6.5). School catchment area was more important than parental social class or housing tenure. Growth in height between 7 and 11 was diminished in infected children by a mean of 1.1 cm (0.3 to 2.0 cm) over four years. This growth reduction was largely confined to girls (1.6 cm over four years), among whom it correlated with salivary IgG (P = 0.015). CONCLUSION: Data from salivary assay to investigate the epidemiology of H pylori suggest that factors relating to the type of community in which the child lives may now be as important for acquisition of this infection as features of the family home. The greater reduction of growth among infected girls raises the possibility that H pylori infection may delay or diminish the pubertal growth spurt. PMID- 7987104 TI - Acyclovir and post-herpetic neuralgia and ocular involvement. PMID- 7987105 TI - Ethnic variation in epidemiology and rehabilitation of hip fracture. PMID- 7987107 TI - Matching. PMID- 7987106 TI - Intercultural consultations: investigation of factors that deter non-English speaking women from attending their general practitioners for cervical screening. AB - OBJECTIVES: To determine the factors that deter ethnic minority women living in east London from attending their general practitioner for cervical cytology screening. DESIGN: Qualitative study by means of focus group discussions between October 1993 and March 1994. SETTING: East London. SUBJECTS: Non-health specific established community groups and specially convened groups of Bengali, Kurdish, Turkish, Urdu and Punjabi, and Chinese speaking women. MAIN OUTCOME MEASURES: The spontaneous views of non-English speaking women resident in east London on cervical screening, focusing on attitudes to screening, their experiences of the cervical cytology screening services as currently provided, and their knowledge and beliefs about cervical screening. RESULTS: Some reported attitudinal barriers to cervical cytology screening such as fear of cancer were not deterrents. Administrative and language barriers were more important, as were inadequate surgery premises and concerns about sterility. CONCLUSION: Contrary to popular belief among general practitioners in east London, women from ethnic minorities are enthusiastic about cervical cytology screening once they understand the purpose of the test and the call and recall procedures. It is possible to consult with community groups in their own language through focus group discussions, working with bilingual health advocates who have had a short practical training in facilitating small group discussions. This form of user consultation could be carried out focusing on other aspects of health promotion. PMID- 7987108 TI - Management of patients after their first myocardial infarction. AB - In the past 20 years there has been a steady improvement in the short term prognosis of patients with myocardial infarction, following the introduction of beta blockers, thrombolysis, and aspirin. Patients treated with thrombolytic drugs have a lower overall mortality after myocardial infarction but remain at risk of non-fatal reinfarction or death, and in one study almost half of all survivors of acute myocardial infarction died or suffered a further ischaemic event within three years. It is therefore important to have a strategy to identify patients at high risk, to reduce the subsequent development of cardiac failure and mortality, and to have effective measures for secondary prevention to reduce the incidence of reinfarction as well as to promote rehabilitation. PMID- 7987109 TI - Cardiac transplantation for AL amyloidosis. PMID- 7987110 TI - Scenario analysis of the future of medicines. AB - Planning future policy for medicines poses difficult problems. The main players in the drug business have their own views as to how the world around them functions and how the future of medicines should be shaped. In this paper we show how a scenario analysis can provide a powerful teaching device to readjust peoples' preconceptions. Scenarios are plausible, not probable or preferable, portraits of alternative futures. A series of four of alternative scenarios were constructed: "sobriety in sufficiency," "risk avoidance," "technology on demand," and "free market unfettered." Each scenario was drawn as a narrative, documented quantitatively wherever possible, that described the world as it might be if particular trends were to dominate development. The medical community and health policy markers may use scenarios to take a long term view in order to be prepared adequately for the future. PMID- 7987112 TI - Patient care and the general practitioner. Joint Working Party of the Welsh Council of the Royal College of General Practitioners and the Welsh General Medical Services Committee. AB - The role of general practitioners is being redefined in the light of the emphasis on more care in the community, economic factors, and patients' expectations. The strength of general practice lies in the doctor-patient relationship; this strength must not be lost sight of. Specific tasks of the general practitioner include the responsibility for the care of individuals; the role of gatekeeper; broad knowledge of curative, preventive; and rehabilitative medicine; teamwork; management; and development of population based strategies. Future work patterns include the general practitioner first and foremost as a clinician and an integrator of health services, but they also involve audit, education and training, research, management, and relations with organisations in the public, private, and voluntary sectors. It is important to make changes only when they benefit patients and to maintain the principle of equity of access to care. PMID- 7987111 TI - The profession of medicine. AB - It seems timely to define the purpose of medicine and examine the concept of a profession. This paper does so in the wider context of health, values in society, and the need to involve patients and the public as a whole. The author looks closely at what doctors do and concludes that making the diagnosis is a key element. The consultation is the building block for resource allocation. In addition to the diagnosis it sets out the prognosis and possible treatment and emphasises the importance of communicating these to the patient. Looking at the kind of doctor we need raises such issues as ethical standards, continuing professional development, team working, clinical standards, quality, outcomes, and research and development. Throughout, the role of education is seen as crucial. Leadership and vision are required by senior members of the profession if the opportunities presented are to be developed further. PMID- 7987113 TI - Public health 2020. AB - The aim of public health is to improve the health of people in communities and in populations (protection from environmental hazards and provision for health needs). The challenge for public health doctors is to re-establish public health leadership of communities, address social and environmental causes of ill health, and link with primary care (a) to improve the health of neighbourhoods and (b) to combine perspectives in commissioning services. Current threats derive from organisational philosophies. For example, focusing on market development does not allow for population based functions and so neglects the main influences on health. The way forward is a network model of organisation in which small teams collaborate with each other to the common good. For example, successful commissioning authorities would have the public health leadership of the director of public health and the support of the chief executive, treasurer, and representatives of primary care, including a medical adviser from the family health services authority. PMID- 7987115 TI - Past and future influences on public health. PMID- 7987114 TI - Over the counter H2 receptor antagonists. Serve only as expensive antacids. PMID- 7987116 TI - Over the counter H2 receptor antagonists. Increase the risks to offshore workers. PMID- 7987117 TI - Effect of dietary mineral salt on blood pressure. Study methods flawed. PMID- 7987118 TI - Issuing private prescriptions to non-exempt patients. Legal loophole exists. PMID- 7987119 TI - Should obesity be treated? Obesity is an anaesthetic risk. PMID- 7987120 TI - Interpreting results of observational research. Requires more, not less, statistical analysis. PMID- 7987121 TI - Interpreting results of observational research. Tools may be blamed for shortcomings of workers. PMID- 7987122 TI - Should obesity be treated? Those who consult should be treated. PMID- 7987123 TI - Implications of supervision registers in psychiatry. Being on the register will not remove the risk. PMID- 7987125 TI - Medical ethics. Justice has a wider scope. PMID- 7987124 TI - Implications of supervision registers in psychiatry. Most patients in Bow and Poplar would be on the register. PMID- 7987126 TI - Medical ethics. The four principles may clash. PMID- 7987127 TI - Assisted suicide for depression. PMID- 7987128 TI - Rebuilding health services in Rwanda. PMID- 7987129 TI - Influence of patients' expectations on disease. PMID- 7987130 TI - Antibodies to phospholipid in alcoholic liver disease. PMID- 7987131 TI - Controlled trials of dental amalgam are needed. PMID- 7987132 TI - Use of complementary therapies. PMID- 7987133 TI - Measles and rubella immunisation campaign. Older children should be included. PMID- 7987134 TI - Measles and rubella immunisation campaign. Is a booster necessary? PMID- 7987135 TI - Measles and rubella immunisation campaign. May have medicolegal consequences. PMID- 7987136 TI - Measles and rubella immunisation campaign. Safety untested. PMID- 7987137 TI - Health costs of social injustice. PMID- 7987138 TI - Tuberculosis in a changing world. PMID- 7987139 TI - While awaiting the next pandemic of influenza A. PMID- 7987140 TI - The referral system. PMID- 7987141 TI - Switching devices and independence of disabled people. PMID- 7987143 TI - Petrol pollution worries royal commission. PMID- 7987142 TI - How technology can help rehabilitation. PMID- 7987144 TI - Malaria tests India's public health system. PMID- 7987145 TI - Television drug advert causes upset in New Zealand. PMID- 7987146 TI - Australian doctors outraged by proposed overhaul. PMID- 7987147 TI - European GPs raise profile. PMID- 7987148 TI - Audit commission criticises mental health services. PMID- 7987150 TI - Wartime evacuation and mortality from childhood leukaemia in England and Wales in 1945-9. AB - OBJECTIVE: To discover whether the wartime government evacuation of children from London and other population centres to rural districts was associated with any increase in childhood leukaemia. DESIGN: Observational study of mortality from leukaemia among the childhood population of England and Wales in relation to the unique population movements during the second world war. The 476 rural districts of England and Wales were ranked according to the ratio of government evacuees (two thirds of them children) to local children in September 1941. The districts were divided into three categories, each with similar numbers of children in 1947 but with different ratios of evacuees to local children ("low," "intermediate," "high"). Mortality from childhood leukaemia was examined in these three rural categories in 1945-9. Urban areas were also examined according to their exposure to evacuees. SETTING: Local authority areas of England and Wales. SUBJECTS: Children aged under 15. RESULTS: 47% excess of leukaemia at ages 0-14 years occurred in 1945-9 in the rural "high" category for evacuees relative to the "low" category, with a significant trend across the three categories. There were increases in both the 0-4 and 5-14 year age groups, but these were larger in the older age group. Rates 25% lower than average occurred in rural areas with few evacuees. CONCLUSION: These findings suggest that wartime evacuation increased the incidence of childhood leukaemia in rural areas and that other forms of population mixing may have contributed to the increases in past decades. Overall, they add to the appreciable evidence for an infective basis in childhood leukaemia. PMID- 7987149 TI - Environmental lead and children's intelligence: a systematic review of the epidemiological evidence. AB - OBJECTIVE: To quantify the magnitude of the relation between full scale IQ in children aged 5 or more and their body burden of lead. DESIGN: A systematic review of 26 epidemiological studies since 1979: prospective studies of birth cohorts, cross sectional studies of blood lead, and cross sectional studies of tooth lead. SETTING: General populations of children > or = 5 years. MAIN OUTCOME MEASURES: For each study, the regression coefficient of IQ on lead, after adjustment for confounders when possible, was used to derive the estimated change in IQ for a specific doubling of either blood or tooth lead. RESULTS: The five prospective studies with over 1100 children showed no association of cord blood lead or antenatal maternal blood lead with subsequent IQ. Blood lead at around age 2 had a small and significant inverse association with IQ, somewhat greater than that for mean blood lead over the preschool years. The 14 cross sectional studies of blood lead with 3499 children showed a significant inverse association overall, but showed more variation in their results and their ability to allow for confounders. The seven cross sectional studies of tooth lead with 2095 children were more consistent in finding an inverse association, although the estimated magnitude was somewhat smaller. Overall synthesis of this evidence, including a meta-analysis, indicates that a typical doubling of body lead burden (from 10 to 20 micrograms/dl (0.48 to 0.97 mumol/l) blood lead or from 5 to 10 micrograms/g tooth lead) is associated with a mean deficit in full scale IQ of around 1-2 IQ points. CONCLUSION: While low level lead exposure may cause a small IQ deficit, other explanations need considering: are the published studies representative; is there inadequate allowance for confounders; are there selection biases in recruiting and following children; and do children of lower IQ adopt behaviour which makes them more prone to lead uptake (reverse causality)? Even if moderate increases in body lead burden adversely affect IQ, a threshold below which there is negligible influence cannot currently be determined. Because of these uncertainties, the degree of public health priority that should be devoted to detecting and reducing moderate increases in children's blood lead, compared with other important social detriments that impede children's development, needs careful consideration. PMID- 7987152 TI - Impact of war on infectious disease in Bosnia-Hercegovina. PMID- 7987151 TI - Apolipoprotein e4 allele and cognitive decline in elderly men. AB - OBJECTIVES: To determine whether polymorphism of apolipoprotein E--notably, the e4 allele--predicts cognitive deterioration in the general population. DESIGN: Population based cohort investigated in 1990 and in 1993. SETTING: Zutphen, the Netherlands. SUBJECTS: Representative cohort of 538 Dutch men aged 70-89 at baseline. MAIN OUTCOME MEASURES: Cognitive function assessed by mini mental state examination, change in cognitive function and incidence of impaired cognitive function at three years. RESULTS: The baseline prevalence of impaired cognitive function (mini mental state examination score < or = 25) was higher among carriers of the e4 allele compared with men without the allele (41.0% (55) v 31.1% (122) P = 0.03), and this result was still valid after adjustment for age, occupation, smoking, alcohol use, and cardiovascular diseases. The decline in cognitive function at three years was largest in men homozygous for e4 (-2.4 points), intermediate in those heterozygous for e4 (-0.7 points), and lowest in men without e4 (-0.1 points), and it was independent of other risk factors (P = 0.02). The risk of developing impaired cognitive function during follow up was significantly increased in allele carriers compared with non-carriers (27.6% (16/58) v 15.5% (32/207)). The adjusted odds ratio was 2.87 (95% confidence interval 1.29 to 6.42). Twenty two per cent of the risk of developing impaired cognitive function in this population may be attributable to the e4 allele. CONCLUSIONS: The apolipoprotein e4 allele predisposes to cognitive decline in a general population of elderly men. PMID- 7987153 TI - Does the type of sewage drainage affect health? PMID- 7987154 TI - Nationwide study of decisions concerning the end of life in general practice in The Netherlands. AB - OBJECTIVE: To gain insight into decisions made in general practice about the end of life. DESIGN: Study I: interviews with 405 physicians. Study II: analysis of death certificates with data obtained on 5197 cases in which decisions about the end of life may have been made. Study III: prospective study with doctors from study I: questionnaires used to collect information about 2257 deaths. The information was representative for all deaths in the Netherlands. RESULTS: Over two fifths of all patients in the Netherlands die at home. General practitioners took fewer decisions about the end of life than hospital doctors and doctors in nursing homes (34%, 40%, and 56% of all dying patients, respectively). Specifically, decisions to withhold or withdraw treatment to prolong life were taken less often. Euthanasia or assisted suicide, however, was performed in 3.2% of all deaths in general practice compared with 1.4% in hospital practice. In over half of the cases concerning pain relief or non-treatment general practitioners did not discuss the decision with the patient, mostly because of incapacity of the patient, but in 20% of cases for "paternalistic" reasons. Older general practitioners discussed such decisions less often with their patients. Colleagues were consulted more often if the general practitioner worked in group practice. CONCLUSION: Differences in work situation between general practitioners and hospital doctors and differences between the group of general practitioners contribute to differences in the number and type of decisions about the end of life as well as in the decision making process. PMID- 7987155 TI - Antiplatelet treatment for thromboprophylaxis: a step forward or backwards? AB - A recent meta-analysis from the Antiplatelet Trialists' Collaboration recommended that antilatelet treatment either alone or, for greater effect, in addition to other proved forms of thromboprophylaxis should be considered for patients at high risk of thromboembolism. This paper argues that the current evidence does not justify the adoption of aspirin or other antiplatelet treatment for venous thromboprophylaxis, especially when more effective alternatives exist. Furthermore, several issues relating to this latest meta-analysis need to be debated. PMID- 7987156 TI - Antiplatelet therapy for thromboprophylaxis: the need for careful consideration of the evidence from randomised trials. Antiplatelet Trialists' Collaboration. PMID- 7987157 TI - Caring for mentally ill people. AB - Despite legislation to harmonise mental health practice throughout Europe and convergence in systems of training there remains an extraordinary diversity in psychiatric practice in Europe. Approaches to tackling substance misuse vary among nations; statistics on psychiatric morbidity are affected by different approaches to diagnosis and treatment of psychiatric disorders; attitudes towards mental illness show definite international differences. Everywhere, though, mental health care for patients with psychotic illnesses is a "cinderella service," and there is a general move towards care falling increasingly on the family and the community. PMID- 7987158 TI - ABC of breast diseases. Management of regional nodes in breast cancer. PMID- 7987159 TI - Cholesterol and violent death. Clinical importance is questionable. PMID- 7987160 TI - Cholesterol and violent death. Diets, violence, and civilization. PMID- 7987161 TI - Cholesterol and violent death. Other studies exist. PMID- 7987162 TI - Cerebral palsy and intrapartum care. Wrong denominator used. PMID- 7987163 TI - Teaching students in the community. PMID- 7987164 TI - Prescribing exercise in general practice. Scheme in East Sussex has a database. PMID- 7987165 TI - Initial management of suspected meningococcal infection. PMID- 7987166 TI - Tuberculosis and slim disease in Africa. PMID- 7987167 TI - GP's opinions about provision of intrapartum care. PMID- 7987168 TI - Laser treatment of palate results in severe postoperative pain. PMID- 7987169 TI - Waiting times in an ophthalmic outpatient clinic. PMID- 7987170 TI - Laparoscopic cholecystectomy in surgical training. PMID- 7987171 TI - Unscientific assertions on treating asthma in general practice. PMID- 7987172 TI - Appropriateness of referrals to hospital. PMID- 7987173 TI - Therapeutic use of bisphosphonates in oncology. PMID- 7987174 TI - Virtual reality surgery in otorhinolaryngology. PMID- 7987175 TI - Imported falciparum malaria. PMID- 7987176 TI - Supervised administration of methadone by pharmacists. PMID- 7987177 TI - Computer training for doctors and students. PMID- 7987178 TI - Sick doctors. Develop existing occupational health services. PMID- 7987180 TI - Sick doctors. Workaholics harm families also. PMID- 7987179 TI - Sick doctors. Existing services need to be coordinated. PMID- 7987181 TI - Alcoholics and liver transplantation: facts, biases, and the future. PMID- 7987183 TI - The Manjakkudi experience: a camp approach towards treating alcoholics. AB - A new approach towards treating alcoholics in a rural population is discussed in this paper. This approach is referred to as the "camp approach". The first such camp was organized in a rural place called Manjakkudi, a village located in Thanjavur District, Tamil Nadu, India. The first camp was held in 1989 and after that three more such camps were conducted in Manjakkudi over a period of 4 years. A total of 105 patients was treated in these camps. Though this treatment programme is similar to the main programme which we follow at T. T. Ranganathan Clinical Research Foundation in the city, slight modifications were made to suit the rural environment. The details of the programme are discussed in this paper. Total abstinence is the goal. This paper examines the results of the four camps conducted at Manjakkudi and attempts to gain an insight into the factors responsible for such a gratifying outcome. PMID- 7987182 TI - Evidence that the type 1/type 2 dichotomy in alcoholism must be re-examined. AB - Studies supporting Cloninger's original Type 1/Type 2 hypothesis for classifying the genetic transmission of alcoholism have sometimes failed to control for important sources of potential bias. First, the environmental effects of parental alcoholism must be distinguished from the genetic effects of parental alcoholism. Secondly, antisocial personality disorder must be distinguished from alcohol dependence. Thirdly, to control for developmental effects a cohort of alcoholics should be followed into late mid-life. The present report, a 50-year prospective study of the development of alcoholism in two community samples of 456 disadvantaged youth and 204 Harvard graduates, addresses these three potential sources of bias. In this report the age of onset of alcoholism and the degree of antisocial symptomatology was correlated with disturbed family environment but was quite independent of the presence or absence of a heredity positive for alcoholism. The reasons why such findings threaten the validity of the Type 1/Type 2 hypothesis are discussed. PMID- 7987184 TI - Transitions between routes of administration of regular amphetamine users. AB - A sample of 301 regular amphetamine users was interviewed regarding transitions between routes of administration of amphetamines. Use of amphetamines by injecting was widespread, with two-thirds (67%) of subjects having injected the drug during the preceding 6 months. Needle-sharing was common, with 41% of injectors having shared a needle in the month preceding interview. A transition to regular amphetamine injecting from other routes of administration was reported by 40% of subjects, with males being twice as likely to report such a transition. The median number of such transitions was one. The main reasons given by subjects for the transition to injecting were liking the "rush" from injecting, and seeing it as a more economical and a healthier way to use. A small proportion of subjects (9%) reported a transition away from injecting amphetamines, with a median of one such transition. The most common reason given for abandoning injecting was concern about vascular damage. Interventions to encourage safer use of amphetamines need to address the misconceptions that injecting is more economical and more healthy, and to emphasize the vascular problems associated with injecting. PMID- 7987185 TI - Sexual behaviour of drug injectors in London: implications for HIV transmission and HIV prevention. AB - The importance of sharing injecting equipment in the transmission dynamics of HIV is well established. Comparatively less is known about the sexual behaviour of drug injectors and the risks posed to themselves and their sexual partners through the sexual transmission of HIV. Findings are reported from survey-based interviews undertaken in 1991 which investigated the sexual behaviour of 516 drug injectors, both in and out of treatment in London. The majority of respondents (80%) were sexually active in the 6 months preceding interview. During this time, respondents had a mean of 2.1 non-commercial opposite sex partners. Most (66%) had vaginal intercourse at least once a week, although 68% never used condoms with primary partners and 34% never used condoms with casual partners. Those having sexual intercourse most often were less likely to use condoms. Many had non-injecting sexual partners, and 62% of respondents' primary and casual partners did not inject drugs. Confirmed saliva HIV test results show 10% of respondents to be antibody positive, with a higher rate of prevalence (14% positive) among those with no experience of treatment. This group were also more likely to report casual sexual intercourse. The average rate of partner change, the high proportion of drug injectors with non-injecting partners and the infrequency of condom use within primary and causal relationships indicates the potential for HIV transmission between injectors and their non-injecting sexual partners. The paper concludes by emphasizing the importance of outreach and community-based intervention in safer sex health promotion. PMID- 7987186 TI - The relationship between cocaine-induced paranoia and compulsive foraging: a preliminary report. AB - Two prominent behavioral syndromes associated with chronic cocaine use that have been described in the literature are cocaine-induced paranoia (CIP) and cocaine induced compulsive foraging (CICF) for cocaine. To help to clarify the relationship between the two cocaine-induced syndromes, the concordance and sequence of onset of the two cocaine-induced behaviors over the course of the patients' lifetime use of cocaine and during the course of a binge was examined in 62 crack cocaine-dependent men. Thirty-four (54.8%) reported experiencing both CIP and CICF. In 18 (29%) of the patients, only one of these cocaine-induced behavioral syndromes was reported. Ten (16.1%) of the subjects reported neither CIP nor CICF. Patterns of cocaine or other substance use and degrees of tolerance to cocaine were not significantly different between the groups endorsing different patterns of cocaine-induced behaviors. CIP typically preceded the onset of CICF both over the course of the patients' lifetime use of cocaine and over the course of a binge. The study results suggest varying thresholds for the expression of these behaviors in chronic cocaine-abusing individuals. PMID- 7987187 TI - The generalizability of the dependence syndrome across substances: an examination of some properties of the proposed DSM-IV dependence criteria. AB - DSM-III-R and proposed DSM-IV schemes for the diagnosis of psychoactive substance use disorders are based largely on the dependence syndrome concept. However, there is an absence of empirical support for the generalizability of the dependence syndrome across substances. This study examines how consistently proposed DSM-IV dependence criteria function to measure dependence across seven substances: alcohol, cannabis, cocaine, stimulants, hallucinogens, sedatives and opiates. Using structured research diagnostic interviews, dependence diagnoses were determined for 295 American subjects in treatment for alcohol/drug problems. Several factor analytic techniques were used to assess whether criteria formed single dimensions and how consistently individual criteria measured dependence across substances. The ability and consistency of criteria to measure a continuum of severity across substances were also assessed. Only subjects who used the substance at least six times were entered in the analyses. Overall, results provide strong support for the DSM approach for alcohol, cannabis, cocaine, stimulants, sedatives and opiates, but not for hallucinogens. Results indicate that a single strong factor adequately described the criteria for these six substances. All criteria loaded strongly and uniformly on single factors indicating that all were good measures of dependence. Criteria provided a dimensional measure of severity based on several indices for these substances. In addition, four criteria provided relatively stable indicators of high or low severity across these substances. Results did not support the use of dependence criteria for hallucinogens as these criteria did not form a single factor. Results suggest that very few hallucinogen users experience an inability to cut down or control use, a key indicator of loss of control. PMID- 7987188 TI - Lifetime DSM-IV diagnosis of alcohol, cannabis, cocaine and opiate dependence: six-month reliability in a multi-site clinical sample. AB - Psychiatric research increasingly emphasizes the diagnosis of symptoms and syndromes on a longitudinal basis. This study tests the reliability of lifetime DSM-IV diagnoses of alcohol, cannabis, cocaine and opiate dependence. The CIDI SAM was administered at intervals not less than six months apart to a multi-site sample of 201 clinical respondents. The reliability of lifetime diagnosis of the syndromes, of the criteria which constitute the syndromes, and of the ages of onset reported for the criteria and for the dependence syndromes as a whole, were studied and the effects of patient characteristics suspected to degrade reliability were examined. There was generally good agreement, statistically, at both the syndrome and criterion level between the two interviews. Lifetime diagnoses for three of the drugs--alcohol, cannabis and opiates--were made at or near levels of agreement generally considered excellent under less strict testing conditions, and cocaine dependence was only marginally below this level. Most criteria showed good reliability and all delivered about equal results when averaged across the four substances, although a relationship between reliability and centrality of the symptom to the individual drug abuse pattern was found. Age of onset was almost uniformly highly reliable. Most patient characteristics bore no detectable relationship to reliability, although patients with multiple drug use patterns may warrant more careful probing by interviewers. Overall, these data indicate that lifetime symptoms and diagnoses can be queried reliably, although they must be reported with less confidence than current state diagnoses. PMID- 7987189 TI - Alcohol dependence criteria in DSM-III-R: presence of symptoms according to degree of severity. AB - According to DSM-III-R a positive diagnosis of alcohol dependence requires the presence of at least three of nine symptoms of a core dependence syndrome. In this study the presence of the nine symptoms according to degree of the severity of dependence is examined in 99 patients (mild, n = 23; moderate, n = 26; and severe, n = 50). It is shown that although the cut-off point for a positive diagnosis of dependence is the presence of "any three" out of nine DSM-III-R criteria, specific symptoms ("excessive drinking", "desire or efforts to control drinking", and "drinking despite major problems") have a high probability of occurrence across the dependence severity range (mild, moderate or severe). Conversely, other symptoms appear prominently only in the more severe cases ("much time devoted to alcohol", "important activities given up", and "drinking to relieve withdrawal"). The results suggest that in the DSM-III-R criteria for alcohol dependence some symptoms are more frequently associated with the diagnosis, while other symptoms are associated with severity of the alcohol dependence disorder. PMID- 7987190 TI - Assisting problem drinkers to change on their own: effect of specific and non specific advice. AB - Problem drinkers (99 males, 41 females) wishing to quit or cut down without professional help received a 60-minute session during which they were assessed and given at random one of these materials: Guidelines, a two-page pamphlet outlining specific methods for achieving abstinence or moderate drinking; Manual, a 30-page booklet describing the methods in the Guidelines; or General Information, a package about alcohol effects. At 12 months follow-up, subjects in the Guidelines and Manual conditions showed significantly greater reductions of heavy days (of 5+ drinks) than subjects in General Information (70% vs. 24%); in addition, significantly fewer subjects in the Guidelines and the Manual conditions expressed need for professional assistance with their drinking (25% vs. 46% in General Information). No main effect of condition or gender was observed on rates of moderate drinkers. At 12 months follow-up, 31% of the men and 43% of the women were rated as moderate drinkers. It was concluded that drinkers intending to cut down on their own derive greater benefit (in terms of their alcohol use) from materials containing specific instructions to develop moderate drinking than from those providing general information on alcohol effects. Clinical and research implications of the findings are discussed. PMID- 7987191 TI - Relationships of measures of alcohol consumption with alcohol-related problems in multiple studies: a research synthesis from the collaborative alcohol-related longitudinal project. AB - Two measures of alcohol consumption were used to predict groups of alcohol problems in 21 general population studies from 11 countries to determine (a) if quantity of drinking per occasion or frequency of drinking per month constituted significant "risk" for alcohol problems, having controlled for each as well as individual-level and aggregate-level variables which might confound these relationships and (b) if these associations were homogeneous across studies. A two-tiered analysis assessed these relationships within each study by modeling age, sex, quantity per occasion and frequency per month as predictors of alcohol problems. Meta-analysis combined test statistics to determine if they were homogeneous across studies. The meta-analysis was repeated, blocking for per capita consumption of alcohol (a trait of nations thought to measure drinking norms) and the female rate of suicide (a trait of nations thought to measure societal-level stress). When only individual-level variables were controlled (age and sex), both quantity and frequency were risk factors for each drinking problem. However, except in the case of the association of quantity with alcohol treatment, the magnitude of these risks were heterogeneous across studies. When blocking for the societal-level traits, each had more relevance for some, but not all, of the relationships between consumption and problems. Particularly striking was the well-documented finding that per capita consumption of alcohol significantly distinguished the relationships of frequency of drinking and health problems (while the female suicide rate did not) and the previously undocumented finding that the female suicide rate significantly distinguished the relationships of both quantity and frequency with treatment (while the per capita consumption of alcohol did not). These findings suggest that the impact of norms and the impact of societal stress in groups have different but significant consequences for the relationships of consumption to problems. PMID- 7987192 TI - Evaluation of two student and teacher involved alcohol prevention programmes. AB - Two versions of a school-based alcohol prevention programme for 7th grade students were evaluated against a non-treated comparison condition. Both programme versions were based on a social-cognitive theory approach to alcohol prevention, and differed in the level of role-specifications for participating teachers and peer leaders. Twelve schools with 955 students in Bergen, Norway, participated in the study. Four schools were randomly assigned to each of the three conditions, and the programme was implemented during 10 class periods over 2 months in Spring, 1992. Pre- and post-test surveys were conducted, assessing alcohol use, as well as cognitive variables related to alcohol use in a specific context (intentions, attitudes, norms and self-efficacy expectations). Results showed that the highly role-specified (HRS) version had a higher degree of student involvement than the less role-specified (LRS) version, indicating that the HRS programme was more successful in engaging students in alcohol prevention activities. A significant difference in programme effectiveness was found, as measured by an overall programme effect across all dependent variables. This effect was explained by significantly more positive outcomes in the HRS version compared to both the LRS and the non-treated conditions, while the LRS version did not differ significantly from the non-treated condition. PMID- 7987193 TI - "Physician heal thyself": drink, temperance and the medical question in the Victorian and Edwardian Church of England, 1830-1914. AB - This paper examines the connection between medical research and temperance from the point of view of the Anglican temperance movement in three periods: (1) 1830 55, when Anglican clergymen resisted teetotalism in favour of moderation, in keeping with accepted medical opinion; (2) 1855-73, when a minority of Anglican teetotal clergymen attempted unsuccessfully to convert the Anglican Church to teetotalism and prohibition, as the medical profession in theory, but not always in practice, discouraged excessive therapeutic reliance on alcohol; and (3) 1873 1914, when the prestigious Church of England Temperance Society, with a dual basis, promoted teetotalism among the majority but affirmed the legitimacy of moderate drinking among the British medical and social elite. PMID- 7987195 TI - [The properties of glycogenolytic enzymes and their activation characteristics in the muscle tissue of vertebrates with different ecologies]. AB - The supramolecular structure of glycogenolytic enzymes on intracellular organelles, their properties, and specific features of their regulation largely depend on ecological factors. Development of an ordered supramolecular structure on a glycogen granule and strength of the bond between its components are determined by temperature and do not depend on the mobility of the species in question. Specific features of activation of the glycogenolytic enzymes are determined by functional properties of the muscle tissue. Studies on a hydrodynamic device have shown relationship between activation of glycogen phosphorylase (EC 2.4.1.1) and glycogen phosphorylase kinase (EC 2.7.1.38) and the mobile activity of fish. PMID- 7987194 TI - [The evolution of the lipid ratios in the blood lipoproteins of animals]. AB - It has been shown that the content of individual lipids and their ratio to phospholipids in blood lipoproteins of various density markedly differs in different classes of vertebrates, these differences being especially distinct for low density lipoproteins (LDL), as compared with high density lipoproteins (HDL2 and HDL3). Specifically, the total concentration of phospholipids and triacylglycerols in LDLs decreases in a sequence from fish to mammals, while the content of cholesterol esters increases, the proportion of cholesterol, cholesterol esters and triacylglycerols markedly increasing when calculated for phospholipids. Hence, it seems that the cholesterol coefficient of atherogenicity increases in the course of evolution of vertebrates. The HDL phosphatidylcholines contain much less fatty acid radicals with the odd number of carbon atoms than the cholesterol esters, this ratio being less distinct in fish as compared with birds or mammals. As a rule, domesticated animals have a higher cholesterol coefficient of atherogenicity than the wild ones, i.e., they are more susceptible to atherosclerosis. PMID- 7987196 TI - [The possible role of fatty acids and their conformation in the realization of the respiratory function and in the adaptations of fish gill membranes and of mammalian lungs]. AB - Fatty acid composition of major phospholipids has been studied in 12 fish and 7 mammalian species. Projections of the fatty acid pairs of these molecules on the plane parallel to the membrane surface have been computed. The projection area of two saturated acids was shown to look like the projection area of its "head", while substitution of one or two saturated acids to unsaturated ones increases the projection area 25%. PMID- 7987197 TI - [The evolutionary kinship of the crystallins of cephalopods and vertebrates with heat-shock proteins and stress-induced proteins]. AB - The lenses of cephalopods and vertebrates are a classical example of convergent evolution. In the course of evolution vertebrates and cephalopods used the same strategy of recruitment of ancestral proteins (primarily enzymes, whose activity is related with stress and detoxification) for structural functions in the lens. Crystallins are defined as water soluble proteins, that form the lenses of cephalopods and vertebrates. In vertebrates, only the beta/gamma-crystallin genes are lens-specific. The other crystallin classes (alpha-, beta-, etc) are overexpressed in the lens, having the various noticeable expression levels in the other tissues as well. Almost all the crystallins, forming squid lens are referred to a single class, namely S-crystallins. The latters are encoded by a family of genes, consisting of at least 10 members S-crystallins of the squid and the octopus are related, but not identical to glutathione S-transferases. S crystallins show no enzymatic activity, though they have 42-44% homology with a squid glutathione-S-transferase (GST), which we have structurally characterized. Genes of GST and S-crystallins have similar exon-intron structures (5-6 exons), whereas their 5' flanking regions are different. Promoters of both of S crystallin genes and of some vertebrate crystallin genes bear the similar regulatory element (AP1-site), that must take part in regulation of their lens specific expression. Besides S-crystallins, octopus lens contains a major polypeptide, omega-crystallin, that was characterized in detail. Though omega crystallin is related to aldehyde dehydrogenase (ALDG), it has no enzymatic activity. Genes coding for omega- and S-crystallins were shown to be expressed only in the lens cells of squid and octopus. In some mammals ALDG is known to serve as a crystallin (eta-crystallin of elephant shrew). Thus, octopus omega crystallin and eta-crystallin of elephant shrew--are the first example of similarity between vertebrate and cephalopod crystallins. PMID- 7987198 TI - [The taxon-specific lens protein of the frog eye: its phylogenetic kinship with the proteins of the NADP-dependent reductase family]. AB - Physicochemical and molecular-biological properties of the proteins from the family of NADP-dependent reductases are reviewed in the article. Physicochemical properties of aldehyde/aldosoreductases are well studied. Information on the genes, coding for these proteins has appeared recently as well. Comparison of the protein structures has revealed, that taxon-specific protein of the frog lens-rho crystallin--is structurally related to the superfamily of NADP-dependent reductases, though it does not have an enzymatic activity. Sequence alignment reveals a set of clusters, conserved in all members of superfamily. Among them there are two highly conserved regions, providing for binding of NADP coenzyme. Secondary structure of the proteins is similar as well. All the members of superfamily predominantly have beta-sheets. Comparison of structural data for proteins, isolated from various organisms from bacterium to human, suggests phylogenetic relatedness of all the members of superfamily, including rho crystallin. All the data presented enable to suppose, that rho-crystallin and other members of superfamily have a common ancestor gene. A set of successive duplications and mutations of the ancestor gene resulted in the appearance of rho crystallin gene, that has lost the enzymatic activity and acquired the ability for tissue specific superexpression in the lens cells. PMID- 7987199 TI - [Oxidative stress as a criterion in environmental assessment]. AB - Environmental changes affect the active oxygen generation and thereby involve the oxidative stress. Estimation of the active oxygen metabolism as a method of biotesting is discussed. The results of measurement of specific superoxide dismutase suggest that this approach may be used for environmental assessment. PMID- 7987201 TI - [The stress mechanisms of mammalian adaptation to an elevated content of radionuclides in the environment]. AB - Analysis of populations of rodents and their stability in radioactively contaminated territories (East Ural radioactive track and regions contaminated after the Chernobyl Nuclear Power Plant accident) suggests that non-specific stability due to the stress mechanisms plays an important role in adaptation of the animals to the life in these regions. According to the published data, the elevated radioresistance of animals in these regions appeared to be due to increased non-specific stability formed by the stress mechanisms. PMID- 7987200 TI - [The correction of disorders of the internal body environment in animals and man by the addition of succinic acid to food]. AB - Succinic acid is involved in correction of energy metabolism as a powerful source of protons and ATP and as an antioxidant. Some food products contain succinic acid, specifically those, whose preparation involves anaerobic processes, and some berries. However many everyday food products are devoid of succinic acid. The lack of succinic acid in food can be compensated by its use as a food additive. It has been shown that consumption of succinic acid by rats results in a decreased weight increment of adult animals kept on abundant sugar diet. Both therapeutical (higher) and nutritive (lower) doses of succinic acid decrease metabolic acidosis and restore the transaminase activity in patients. The both metabolic parameters indicate correction of energy metabolism. PMID- 7987202 TI - [Mathematical modelling of the metabolism of the radionuclide cesium-137. The calculation of the population risk]. AB - Detailed mathematical analysis of the metabolism of cesium-137, which first appeared in the environment as a result of nuclear weapon testing in the atmosphere, made it possible to estimate the irradiation for the population of the U.S.A. with reference to sex and age during the entire life until death. In parallel, demographic analysis of mortality due to leucosis from 1950 until 1986 has shown cohorts of elevated mortality risk in two age groups: 0-1 and 45-54 years, starting from 1953. The radiation component of mortality was plotted for a set of cohorts as a function of the irradiation dose until the moment of death. Additional mortality risk was calculated for 1963 and 1967: 5.9 and 2.3 additional deaths per 1000 subjects per 1 Gy, respectively. The potential of demographic methods for assessment of the ecological situation has been shown. PMID- 7987203 TI - [The effect of space flight factors on the peripheral blood in the newt Pleurodeles waltlii]. AB - The effects of space flight factors (SFF) on the peripheral blood in Pleurodeles waltlii were assessed after 12-day flight on board of the biosatellite "Kosmos 2229". These animals were also used to study regeneration of the limb, tail and lens. The corresponding control groups of animals allowed to distinguish between the effects of the operation, non-specific and specific SFFs: (1) basal control operated animals; (2) synchronous control-operated animals kept on the Earth under the same conditions as the flight group, and (3) intact animals. It has been shown that the relative content of neutrophils (mostly, young forms) increased and the proportion of lymphocytes and eosinophils decreased under the influence of SFFs, while the capacity of blood cells for DNA synthesis was not affected. A conclusion has been drawn that the Spanish newts can be used for adequate studies of the SFF effects on the hemopoietic tissue. PMID- 7987204 TI - [The peripheral blood of frogs in the genus Rana as a test system for assessing environmental pollution]. AB - Differential analysis of leukocytes was carried out peripheral blood smears of the frogs from four localities in the territory adjacent to a chemical plant in the Novgorod District (Rana temporaria) and two localities with an increased radiation background in the Bryansk District (R. lessonae and R. esculenta). Marked and similar changes in the content of neutrophilic and eosinophilic granulocytes were found in the frogs from all studied localities. A pronounced neutropenia was noted, which was often accompanied by the appearance of immature forms of the neutrophilic series. We propose that these changes are due selective damage of the entire series of differentiation of neutrophilic granulocytes, including the precursor cells. The increased percentage of eosinophilic granulocytes and appearance, in some cases, of immature cells are considered as signs of protective (antitoxic and antimicrobial) response. PMID- 7987205 TI - [The evaluation of the embryotoxicity of the aqueous environment]. AB - A highly sensitive express method has been proposed for assessment of embryotoxicity of the aqueous medium under the conditions of anthropogenic pollution. Amphibian embryos were used as test objects for estimating the level of free radical processes during adaptation stress. The method can be used under the field conditions and is proposed as a part of ecological monitoring of natural waters. PMID- 7987206 TI - [The characteristics of the effect of space flight factors on regeneration processes in mammals and Urodela]. AB - Comparative analysis of experimental studies on regeneration of bone and muscle tissue under the influence of space flight factors (SFF) during restoration of experimental fracture in rats and epimorphic limb regeneration in adult newt is presented SFF-induced retardation of regeneration in mammals and its acceleration in tailed amphibians results from changed calcium metabolism in conditions of microgravity. Bidirectional effect of SFF on bone regeneration is due to specific control of calcium homeostasis in these taxa. Upon termination of the space flight (SF) the Wistar SPF rats proved to have increased functional activity of parathyrocytes and blocked calcitonin secretion to the blood by the C-cells of thyroid gland. Hence, inhibition of posttraumatic bone regeneration in rats is due to decreased formation rate and enhanced resorption of bony tissue. Sharp decrease of the calcitonincytes population following the initial hypertrophy of ultimobranchial gland (UBG) is observed in adult newt Pleurodeles waltlii Michah during SF. Progressing demineralization of skeletal elements including the amputated limb stump accelerates the first stages of its regeneration in conditions of SF. PMID- 7987207 TI - [Ontogenetic transformations in the energy metabolism system of the skeletal muscles under different conditions of animal development]. AB - Age-related changes in the general activity of creatin kinase (CrK), mitochondrial fraction of this enzyme (CrKmit), general activity of lactate dehydrogenase (LDH) and its anaerobic fractions (LDHan), content and ratio of cytochromes of the mitochondrial respiration chain, respiration rate of isolated mitochondria on various substrates in the 3rd state have been studied in the skeletal muscle of Wistar rats developing under the conditions of normo- (NK) and hypokinesia (HK). General patterns of changes in these indices have been shown, that do not depend on the conditions of animal development: the minimal CrK and CrKmit activity and increased saturation of the respiration chain with cytochrome b562 during the playing period, days 30 to 40 of postnatal period. The highest level of cytochrome aa3 was observed in the peak of sexual maturation (Day 45). However the conditions of development affect the timing of extreme indices and their level in adult animals. For example, in the animals developing under the NK conditions the highest saturation of the respiration chain with cytochrome b562 was observed on Day 30, while in those developing under the HK conditions by five days later. In 30-day old rats from the NK group the cytochrome aa3 content of skeletal muscle was almost maximal, while in the HK group the maximum was observed only at the peak of sexual maturation. In the adult animals of the HK group the activity of CrKmit, LDH and LDHan was higher, while the content of cytochrome aa3 and saturation of the respiration chain with cytochrome b562 was lower. A lesser b562/aa3 ratio is related to the predominance of NADH2-dependent electron transport pathways of oxidation in the mitochondria from the rat skeletal muscle. Thus, the conditions of development in the early postnatal period, especially during the playing period, determine the state of energy metabolism in the adult skeletal muscle. PMID- 7987208 TI - [The participation of neurotransmitters in the regulation of the motor activity of the chick embryo amnion]. AB - The authors' data on time-related changes in the contractile activity of non innervated smooth muscle amnion of the chick embryo devoid of blood vessels and on involvement of the amniotic fluid neurotransmitters in regulation of the amnion motor activity have been summarized. A scheme of possible mechanism underlying regulation of the spontaneous rhythmic contractile activity of the amnion by two antagonistic neurotransmitters present in the amniotic fluid: serotonin and noradrenalin, which stimulate and inhibit the amnion motor activity, respectively. The results of experiments on successive block of the serotonin and adrenergic receptors by introduction of the corresponding antagonists in the chick embryo amniotic fluid speak in favor of the proposed scheme of humoral regulation of the amnion motor activity. A possible involvement of this humoral mechanism in the inhibitory effect of increased carbon dioxide content of the air on the amnion motor activity has been considered. PMID- 7987209 TI - [The modifying cytogenetic effects of gossypol and its derivatives]. AB - The method of micronuclei account allowed to demonstrate protective effect of gossypol and its derivatives megacin and batriden of chromosomes of rat male germ cells from mutagenic effect of nitrosomethylurea (NMU) and, conversely, enhancement of clastogenic effect of another alkylating agent, fotrin. Strong antimutagenic effect of gossypol from NMU was also observed in external granular layer of young rat cerebellum. Possible mechanisms of antimutagenic action of this unique polyphenol of cotton plant are discussed. PMID- 7987211 TI - The pharmacophore of the human C5a anaphylatoxin. AB - We have determined which amino acids contribute to the pharmacophore of human C5a, a potent inflammatory mediator. A systematic mutational analysis of this 74 amino acid protein was performed and the effects on the potency of receptor binding and of C5a-induced intracellular calcium ion mobilization were measured. This analysis included the construction of hybrids between C5a and the homologous but unreactive C3a protein and site-directed mutagenesis. Ten noncontiguous amino acids from the structurally well-defined 4-helix core domain (amino acids 1-63) and the C-terminal arginine-containing tripeptide were found to contribute to the pharmacophore of human C5a. The 10 mostly charged amino acids from the core domain generally made small incremental contributions toward binding affinity, some of which were independent. Substitutions of the C-terminal amino acid Arg 74 produced the largest single effect. We also found the connection between these 2 important regions to be unconstrained. PMID- 7987210 TI - Collectins--soluble proteins containing collagenous regions and lectin domains- and their roles in innate immunity. AB - The collectins are a group of mammalian lectins containing collagen-like regions. They include mannan binding protein, bovine conglutinin, lung surfactant protein A, lung surfactant protein D, and a newly discovered bovine protein named collectin-43. These proteins share a very similar modular domain composition and overall 3-dimensional structure. They also appear to play similar biological roles in the preimmune defense against micro-organisms in both serum and lung surfactant. The close evolutionary relationship between the collectins is further emphasized by a common pattern of exons in their genomic structures and the presence of a gene cluster on chromosome 10 in humans that contains the genes known for the human collectins. Studies on the structure/function relationships within the collectins could provide insight into the properties of a growing number of proteins also containing collagenous regions such as C1q, the hibernation protein, the alpha- and beta-ficolins, as well as the membrane acetylcholinesterase and the macrophage scavenger receptor. PMID- 7987212 TI - Primary structure and functional characterization of rat C5a: an anaphylatoxin with unusually high potency. AB - The anaphylatoxin C5a is a pro-inflammatory factor generated from C5 during complement activation. C5a derived from rat C5 exhibits significantly greater potency compared to C5a from other species. Rat C5a was 25-fold more potent than human C5a for eliciting spasmogenic contraction of guinea pig ileum. Proteolytic removal of the C-terminal arginine of C5a (C5adesArg) reduced spasmogenic potency of rat C5a by only 4-fold compared to a 3,000-fold reduction for human C5adesArg. In addition, rat C5adesArg was 50-fold more potent than human C5adesArg in a guinea pig vascular permeability (in vivo) assay and as a chemotactic factor for human neutrophils. C5a and C5adesArg were purified from zymosan-activated rat serum. Rat C5a, like human C5a, is glycosylated but contains 77 amino acid residues instead of the 74 residues of human C5a. Comparison of the primary structures of rat and human C5a indicated differences at 30 positions including an insert of 3 residues (LLH) in the rat molecule between residue positions 3 and 4 in human C5a. Insertion of residues LLH between Gln-3 and Lys-4 in a recombinant human C5a molecule using site-directed mutagenesis failed to enhance potency. Synthetic C-terminal analogues of rat C5a proved to be measurably more potent than the corresponding human C5a analogues (Ember JA et al., 1993, Protein Sci 2(Suppl 1):159 [Abstr]). We conclude that multiple sequence differences in the C-terminal effector portion and/or elsewhere in rat C5a, but not the LLH insert, account for the significant enhancement in potency of rat C5a over C5a from other species. PMID- 7987213 TI - Laue and monochromatic diffraction studies on catalysis in phosphorylase b crystals. AB - The conversion of substrate, heptenitol, to product, beta-1-C-methyl, alpha-D glucose-1-phosphate (heptulose-2-P), in crystals of glycogen phosphorylase b has been studied by Laue and monochromatic diffraction methods. The phosphorolysis reaction in the crystal was started following liberation of phosphate from a caged phosphate compound, 3,5-dinitrophenyl phosphate (DNPP). The photolysis of DNPP, stimulated by flashes from a xenon flash lamp, was monitored in the crystal with a diode array spectrophotometer. In the Laue diffraction experiments, data to 2.8 A resolution were collected and the first time shot was obtained at 3 min from the start of reaction, and data collection comprised three 800-ms exposures. Careful data processing of Laue photographs for the large enzyme resulted in electron density maps of almost comparable quality to those produced by monochromatic methods. The difference maps obtained from the Laue measurements showed that very little catalysis had occurred 3 min and 1 h after release of phosphate, and a distinct peak consistent with the position expected for phosphate, in the attacking position was observed. Data collection times with monochromatic crystallographic methods on a home source took 16 h for data to 2.3 A resolution. Sufficient phosphate was released from the caged phosphate in the crystal from 5 flashes with a xenon flashlamp within 1 min for the reaction to go to completion within the time scale of the monochromatic data collection procedures. The heptulose-2-P product complex has been refined and the model agrees with that obtained previously with the major difference that the interchange of an aspartic acid (Asp 283) by an arginine (Arg 569) was not observed at the catalytic site. This change is part of the activation process of glycogen phosphorylase and may not have taken place in the current experiments because the caged compound binds weakly at the inhibitor site, restricting conformational change, and because activators of the enzymic reaction were not present in the crystal. In experiments with monochromatic radiation in which low phosphate concentrations were generated either by fewer photons or by diffusion of known phosphate concentrations, mixtures of substrate and product were observed. It was not possible through crystallographic refinement at 2.3 A resolution to establish the fractional occupancies of the enzyme-substrate and enzyme-product complexes, but the results did indicate that the reaction was proceeding slowly, consistent with approximate calculations for the likely rate of the reaction in the crystal.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7987214 TI - A survey of furin substrate specificity using substrate phage display. AB - The substrate specificity of furin, a mammalian enzyme involved in the cleavage of many constitutively expressed protein precursors, was studied using substrate phage display. In this method, a multitude of substrate sequences are displayed as fusion proteins on filamentous phage particles and ones that are cleaved can be purified by affinity chromatography. The cleaved phage are propagated and submitted to additional rounds of protease selection to further enrich for good substrates. DNA sequencing of the cleaved phage is used to identify the substrate sequence. After 6 rounds of sorting a substrate phage library comprising 5 randomized amino acids (xxxxx), virtually all clones had an RxxR motif and many had Lys, Arg, or Pro before the second Arg. Nine of the selected sequences were assayed using a substrate-alkaline phosphatase fusion protein system. All were cleaved after the RxxR, and some substrates with Pro or Thr in P2 were also found to be cleaved as efficiently as RxKR or RxRR. To further elaborate surrounding determinants, we constructed 2 secondary libraries (xxRx(K/R)Rx and xxRxPRx). Although no consensus developed for the latter library, many of the sequences in the the former library had the 7-residue motif (L/P)RRF(K/R)RP, suggesting that the furin recognition sequence may extend over more than 4 residues. These studies further clarify the substrate specificity of furin and suggest the substrate phage method may be useful for identifying consensus substrate motifs in other protein processing enzymes. PMID- 7987215 TI - Properties of a recombinant human hemoglobin double mutant: sickle hemoglobin with Leu-88(beta) at the primary aggregation site substituted by Ala. AB - A recombinant double mutant of hemoglobin (Hb), E6V/L88A(beta), was constructed to study the strength of the primary hydrophobic interaction in the gelation of sickle Hb, i.e., that between the mutant Val-6(beta) of one tetramer and the hydrophobic region between Phe-85(beta) and Leu-88(beta) on an adjacent tetramer. Thus, a construct encoding the donor Val-6(beta) of the expressed recombinant HbS and a second mutation encoding an Ala in place of Leu-88(beta) was assembled. The doubly mutated beta-globin gene was expressed in yeast together with the normal human alpha-chain, which is on the same plasmid, to produce a soluble Hb tetramer. Characterizations of the Hb double mutant by mass spectrometry, by HPLC, and by peptide mapping of tryptic digests of the mutant beta-chain were consistent with the desired mutations. The absorption spectra in the visible and the ultraviolet regions were practically superimposable for the recombinant Hb and the natural Hb purified from human red cells. Circular dichroism studies on the overall structure of the recombinant Hb double mutant and the recombinant single mutant, HbS, showed that both were correctly folded. Functional studies on the recombinant double mutant indicated that it was fully cooperative. However, its gelation concentration was significantly higher than that of either recombinant or natural sickle Hb, indicating that the strength of the interaction in this important donor-acceptor region in sickle Hb was considerably reduced even with such a conservative hydrophobic mutation. PMID- 7987217 TI - Buried waters and internal cavities in monomeric proteins. AB - We have analyzed the buried water molecules and internal cavities in a set of 75 high-resolution, nonhomologous, monomeric protein structures. The number of hydrogen bonds formed between each water molecule and the protein varies from 0 to 4, with 3 being most common. Nearly half of the water molecules are found in pairs or larger clusters. Approximately 90% are shown to be associated with large cavities within the protein, as determined by a novel program, PRO_ACT. The total volume of a protein's large cavities is proportional to its molecular weight and is not dependent on structural class. The largest cavities in proteins are generally elongated rather than globular. There are many more empty cavities than hydrated cavities. The likelihood of a cavity being occupied by a water molecule increases with cavity size and the number of available hydrogen bond partners, with each additional partner typically stabilizing the occupied state by 0.6 kcal/mol. PMID- 7987216 TI - Properties of a recombinant human hemoglobin with aspartic acid 99(beta), an important intersubunit contact site, substituted by lysine. AB - Site-directed mutagenesis of an important subunit contact site, Asp-99(beta), by a Lys residue (D99K(beta)) was proven by sequencing the entire beta-globin gene and the mutant tryptic peptide. Oxygen equilibrium curves of the mutant hemoglobin (Hb) (2-15 mM in heme) indicated that it had an increased oxygen affinity and a lowered but significant amount of cooperativity compared to native HbA. However, in contrast to normal HbA, oxygen binding of the recombinant mutant Hb was only marginally affected by the allosteric regulators 2,3 diphosphoglycerate or inositol hexaphosphate and was not at all responsive to chloride. The efficiency of oxygen binding by HbA in the presence of allosteric regulators was limited by the mutant Hb. At concentrations of 0.2 mM or lower in heme, the mutant D99K(beta) Hb was predominantly a dimer as demonstrated by gel filtration, haptoglobin binding, fluorescence quenching, and light scattering. The purified dimeric recombinant Hb mutant exists in 2 forms that are separable on isoelectric focusing by about 0.1 pH unit, in contrast to tetrameric hemoglobin, which shows 1 band. These mutant forms, which were present in a ratio of 60:40, had the same masses for their heme and globin moieties as determined by mass spectrometry. The elution positions of the alpha- and beta-globin subunits on HPLC were identical. Circular dichroism studies showed that one form of the mutant Hb had a negative ellipticity at 410 nm and the other had positive ellipticity at this wavelength. The findings suggest that the 2 D99K(beta) recombinant mutant forms have differences in their heme-protein environments. PMID- 7987218 TI - Ligation alters the pathway of urea-induced denaturation of the catalytic trimer of Escherichia coli aspartate transcarbamylase. AB - We have examined the pathway and energetics of urea-induced dissociation and unfolding of the catalytic trimer (c3) of aspartate transcarbamylase from Escherichia coli at low temperature in the absence and presence of carbamyl phosphate (CP; a substrate), N-(phosphonacetyl)-L-Asp (PALA; a bisubstrate analog), and 2 anionic inhibitors, Cl- and ATP, by analytical gel chromatography supplemented by activity assays and ultraviolet difference spectroscopy. In the absence of active-site ligands and in the presence of ATP, c3 dissociates below 2 M urea into swollen c chains that then gradually unfold from 2 to 6 M urea with little apparent cooperativity. Linear extrapolation to 0 M urea of free energies determined in 3 independent types of experiments yields estimates for delta Gdissociation at 7.5 degrees C of about 7-10 kcal m-1 per interface. delta Gunfolding of dissociated chains when modeled as a 2-state process is estimated to be very small, on the order of -2 kcal m-1. The data are also consistent with the possibility that the unfolding of the dissociated monomer is a 1-state swelling process. In the presence of the ligands CP and PALA, and in the presence of Cl-, c3 dissociates at much higher urea concentrations, and trimer dissociation and unfolding occur simultaneously and apparently cooperatively, at urea concentrations that increase with the affinity of the ligand. PMID- 7987219 TI - Reversible unfolding of fructose 6-phosphate, 2-kinase:fructose 2,6 bisphosphatase. AB - Reversible unfolding of rat testis fructose 6-phosphate,2-kinase:fructose 2,6 bisphosphatase in guanidine hydrochloride was monitored by following enzyme activities as well as by fluorescence methodologies (intensity, emission maximum, polarization, and quenching), using both intrinsic (tryptophan) and extrinsic (5((2-(iodoacetyl)amino) ethyl)naphthalene-1-sulfonic acid) probes. The unfolding reaction is described minimally as a 4-state transition from folded dimer- >partially unfolded dimer-->monomer-->unfolded monomer. The partially unfolded dimer had a high phosphatase/kinase ratio due to preferential unfolding of the kinase domain. The renaturation reaction proceeded by very rapid conversion (less than 1 s) of unfolded monomer to dimer, devoid of any enzyme activity, followed by slow (over 60 min) formation of the active enzyme. The recovery rates of the kinase and the phosphatase were similar. Thus, the refolding appeared to be a reversal of the unfolding pathway involving different forms of the transient dimeric intermediates. Fluorescence quenching studies using iodide and acrylamide showed that the tryptophans, including Trp-15 in the N-terminal peptide, were only slightly accessible to iodide but were much more accessible to acrylamide. Fructose 6-phosphate, but not ATP or fructose 2,6-bisphosphate, diminished the iodide quenching, but all these ligands inhibited the acrylamide quenching by 25%. These results suggested that the N-terminal peptide (containing a tryptophan) was not exposed on the protein surface and may play an important role in shielding other tryptophans from solvent. PMID- 7987220 TI - Stability of yeast iso-1-ferricytochrome c as a function of pH and temperature. AB - Absorbance-detected thermal denaturation studies of the C102T variant of Saccharomyces cerevisiae iso-1-ferricytochrome c were performed between pH 3 and 5. Thermal denaturation in this pH range is reversible, shows no concentration dependence, and is consistent with a 2-state model. Values for free energy (delta GD), enthalpy (delta HD), and entropy (delta SD) of denaturation were determined as functions of pH and temperature. The value of delta GD at 300 K, pH 4.6, is 5.1 +/- 0.3 kcal mol-1. The change in molar heat capacity upon denaturation (delta Cp), determined by the temperature dependence of delta HD as a function of pH (1.37 +/- 0.06 kcal mol-1 K-1), agrees with the value determined by differential scanning calorimetry. pH-dependent changes in the Soret region indicate that a group or groups in the heme environment of the denatured protein, probably 1 or both heme propionates, ionize with a pK near 4. The C102T variant exhibits both enthalpy and entropy convergence with a delta HD of 1.30 kcal mol-1 residue-1 at 373.6 K and a delta SD of 4.24 cal mol-1 K-1 residue-1 at 385.2 K. These values agree with those for other single-domain, globular proteins. PMID- 7987221 TI - Stability and peptide binding affinity of an SH3 domain from the Caenorhabditis elegans signaling protein Sem-5. AB - We have determined the thermodynamic stability and peptide binding affinity of the carboxy-terminal Src homology 3 (SH3) domain from the Caenorhabditis elegans signal-transduction protein Sem-5. Despite its small size (62 residues) and lack of disulfide bonds, this domain is highly stable to thermal denaturation--at pH 7.3, the protein has a Tm of 73.1 degrees C. Interestingly, the protein is not maximally stable at neutral pH, but reaches a maximum at around pH 4.7 (Tm approximately equal to 80 degrees C). Increasing ionic strength also stabilizes the protein, suggesting that 1 or more carboxylate ions are involved in a destabilizing electrostatic interaction. By guanidine hydrochloride denaturation, the protein is calculated to have a free energy of unfolding of 4.1 kcal/mol at 25 degrees C. We have also characterized binding of the domain to 2 different length proline-rich peptides from the guanine nucleotide exchange factor, Sos, one of Sem-5's likely physiological ligands in cytoplasmic signal transduction. Upon binding, these peptides cause about a 2-fold increase in fluorescence intensity. Both bind with only modest affinities (Kd approximately equal to 30 microM), lower than some previous estimates for SH3 domains. By fluorescence, the domain also appears to associate with the homopolymer poly-L-proline in a similar fashion. PMID- 7987222 TI - Two-step selective formation of three disulfide bridges in the synthesis of the C terminal epidermal growth factor-like domain in human blood coagulation factor IX. AB - The 45-residue C-terminal EGF-like domain in human blood coagulation factor IX has been synthesized by a 2-step method to form selectively 3 disulfide bridges. Four out of 6 cysteines are blocked with either trityl or 4-methyl-benzyl, and the remaining 2 cysteines are blocked with acetamidomethyl (Acm). In the first step, 4 free cysteinyl thiols are released concurrently with the removal of all protecting groups except Acm and are oxidized to form 1 of the 3 possible isomers containing 2 pairs of disulfides. In the second step, iodine is used to remove the Acm groups to yield the third disulfide bridge. This approach reduces the number of possible disulfide bridging patterns from 15 to 3. To determine the optimal protecting group strategy, 3 peptides are synthesized, each with Acm blocking 1 of the 3 pairs of cysteines involved in disulfide bridges: Cys5 to Cys16 (Cys 1-3), Cys12 to Cys26 (Cys 2-4), or Cys28 to Cys41 (Cys 5-6). Only the peptide having the Cys 2-4 pair blocked with Acm forms the desired disulfide isomer (Cys 1-3/5-6) in high yield after the first step folding, as identified by proteolytic digestion in conjunction with mass spectrometric peptide mapping. Thus, the choice of which pair of cysteines to block with Acm is critically important. In the case of EGF-like peptides, it is better to place the Acm blocking groups on one of the pairs of cysteines involved in the crossing of disulfide bonds. PMID- 7987223 TI - A negative electrostatic determinant mediates the association between the Escherichia coli trp repressor and its operator DNA. AB - The electrostatic potential surfaces were characterized for trp repressor models that bind to DNA with sequence specificity, without specificity, and not at all. Comparisons among the surfaces were used to isolate protein surface features likely to be important in DNA binding. Models that differ in protein conformation and tryptophan-analogue binding consistently showed positive potential associated with the protein surfaces that interact with the DNA major groove. However, negative potential is associated with the trp repressor surface that contacts the DNA minor groove. This negative potential is significantly neutralized in the protein conformation that is bound to DNA. Positive potential is also associated with the tryptophan binding-site surface, a consequence of the tryptophan- or tryptophan analogue-induced allosteric change. This protein region is complementary to the strongest negative potential associated with the DNA phosphate backbone and is also present in the isolated protein structure from the protein-DNA complex. The effects of charge-change mutation, pH dependence, and salt dependence on the electrostatic potential surfaces were also examined with regard to their effects on protein-DNA binding constants. A consistent model is formed that defines a role for long-range electrostatics early in the protein-DNA association process and complements previous structural, molecular association, and mutagenesis studies. PMID- 7987224 TI - Determination of the structure of the DNA binding domain of gamma delta resolvase in solution. AB - The DNA binding domain (DBD) of gamma delta resolvase (residues 141-183) is responsible for the interaction of this site-specific DNA recombinase with consensus site DNA within the gamma delta transposable element in Escherichia coli. Based on chemical-shift comparisons, the proteolytically isolated DBD displays side-chain interactions within a hydrophobic core that are highly similar to those of this domain when part of the intact enzyme (Liu T, Liu DJ, DeRose EF, Mullen GP, 1993, J Biol Chem 268:16309-16315). The structure of the DBD in solution has been determined using restraints obtained from 2-dimensional proton NMR data and is represented by 17 conformers. Experimental restraints included 458 distances based on analysis of nuclear Overhauser effect connectivities, 17 phi and chi 1 torsion angles based on analysis of couplings, and 17 backbone hydrogen bonds determined from NH exchange data. With respect to the computed average structure, these conformers display an RMS deviation of 0.67 A for the heavy backbone atoms and 1.49 A for all heavy atoms within residues 149 180. The DBD consists of 3 alpha-helices comprising residues D149-Q157, S162 T167, and R172-N183. Helix-2 and helix-3 form a backbone fold, which is similar to the canonical helix-turn-helix motif. The conformation of the NH2-terminal residues, G141-R148, appears flexible in solution. A hydrophobic core is formed by side chains donated by essentially all hydrophobic residues within the helices and turns. Helix-1 and helix-3 cross with a right-handed folding topology. The structure is consistent with a mechanism of DNA binding in which contacts are made by the hydrophilic face of helix-3 in the major groove and the amino terminal arm in the minor groove. This structure represents an important step toward analysis of the mechanism of DNA interaction by gamma delta resolvase and provides initial structure-function comparisons among the divergent DBDs of related resolvases and invertases. PMID- 7987225 TI - Deuterium exchange of alpha-helices and beta-sheets as monitored by electrospray ionization mass spectrometry. AB - Deuterium exchange was monitored by electrospray ionization mass spectrometry (ESI-MS) to study the slowly exchanging (hydrogen bonded) peptide hydrogens of several alpha-helical peptides and beta-sheet proteins. Polypeptides were synthetically engineered to have mainly disordered, alpha-helical, or beta-sheet structure. For 3 isomeric 31-residue alpha-helical peptides, the number of slowly exchanging hydrogens as measured by ESI-MS in 50% CF3CD2OD (pD 9.5) provided estimates of their alpha-helicities (26%, 40%, 94%) that agreed well with the values (17%, 34%, 98%) measured by circular dichroic spectroscopy in the same nondeuterated solvent. For 3 betabellins containing a pair of beta-sheets and a related disordered peptide, their order of structural stability (12D > 12S > 14D > 14S) shown by their deuterium exchange rates in 10% CD3OD/0.5% CD3CO2D (pD 3.8) as measured by ESI-MS was the same as their order of structural stability to unfolding with increasing temperature or guanidinium chloride concentration as measured by circular dichroic spectroscopy in water. Compared to monitoring deuterium exchange by proton NMR spectrometry, monitoring deuterium exchange by ESI-MS requires much less sample (1-50 micrograms), much shorter analysis time (10-90 min), and no chemical quenching of the exchange reaction. PMID- 7987226 TI - Recognition of related proteins by iterative template refinement (ITR). AB - Predicting the structural fold of a protein is an important and challenging problem. Available computer programs for determining whether a protein sequence is compatible with a known 3-dimensional structure fall into 2 categories: (1) structure-based methods, in which structural features such as local conformation and solvent accessibility are encoded in a template, and (2) sequence-based methods, in which aligned sequences of a set of related proteins are encoded in a template. In both cases, the programs use a static template based on a predetermined set of proteins. Here, we describe a computer-based method, called iterative template refinement (ITR), that uses templates combining structure based and sequence-based information and employs an iterative search procedure to detect related proteins and sequentially add them to the templates. Starting from a single protein of known structure, ITR performs sequential cycles of database search to construct an expanding tree of templates with the aim of identifying subtle relationships among proteins. Evaluating the performance of ITR on 6 proteins, we found that the method automatically identified a variety of subtle structural similarities to other proteins. For example, the method identified structural similarity between arabinose-binding protein and phosphofructokinase, a relationship that has not been widely recognized. PMID- 7987227 TI - The sequence of a subtilisin-type protease (aerolysin) from the hyperthermophilic archaeum Pyrobaculum aerophilum reveals sites important to thermostability. AB - The hyperthermophilic archaeum Pyrobaculum aerophilum grows optimally at 100 degrees C and pH 7.0. Cell homogenates exhibit strong proteolytic activity within a temperature range of 80-130 degrees C. During an analysis of cDNA and genomic sequence tags, a genomic clone was recovered showing strong sequence homology to alkaline subtilisins of Bacillus sp. The total DNA sequence of the gene encoding the protease (named "aerolysin") was determined. Multiple sequence alignment with 15 different serine-type proteases showed greatest homology with subtilisins from gram-positive bacteria rather than archaeal or eukaryal serine proteases. Models of secondary and tertiary structure based on sequence alignments and the tertiary structures of subtilisin Carlsberg, BPN', thermitase, and protease K were generated for P. aerophilum subtilisin. This allowed identification of sites potentially contributing to the thermostability of the protein. One common transition put alanines at the beginning and end of surface alpha-helices. Aspartic acids were found at the N-terminus of several surface helices, possibly increasing stability by interacting with the helix dipole. Several of the substitutions in regions expected to form surface loops were adjacent to each other in the tertiary structure model. PMID- 7987228 TI - A new family of carbon-nitrogen hydrolases. AB - Using computer methods for database search and multiple alignment, statistically significant sequence similarities were identified between several nitrilases with distinct substrate specificity, cyanide hydratases, aliphatic amidases, beta alanine synthase, and a few other proteins with unknown molecular function. All these proteins appear to be involved in the reduction of organic nitrogen compounds and ammonia production. Sequence conservation over the entire length, as well as the similarity in the reactions catalyzed by the known enzymes in this family, points to a common catalytic mechanism. The new family of enzymes is characterized by several conserved motifs, one of which contains an invariant cysteine that is part of the catalytic site in nitrilases. Another highly conserved motif includes an invariant glutamic acid that might also be involved in catalysis. PMID- 7987229 TI - Protein identification in DNA databases by peptide mass fingerprinting. AB - Proteins can be identified using a set of peptide fragment weights produced by a specific digestion to search a protein database in which sequences have been replaced by fragment weights calculated for various cleavage methods. We present a method using multidimensional searches that greatly increases the confidence level for identification, allowing DNA sequence databases to be examined. This method provides a link between 2-dimensional gel electrophoresis protein databases and genome sequencing projects. Moreover, the increased confidence level allows unknown proteins to be matched to expressed sequence tags, potentially eliminating the need to obtain sequence information for cloning. Database searching from a mass profile is offered as a free service by an automatic server at the ETH, Zurich. For information, send an electronic message to the address cbrg/inf.ethz.ch with the line: help mass search, or help all. PMID- 7987230 TI - [Hydrochloride of the peptide Boc-Gly-Pro-Arg-OMe--a selective inhibitor of thrombin- and epinephrine-induced platelet aggregation]. PMID- 7987231 TI - [Characteristics of murine chromosome 17 containing three tumor necrosis factor family genes, including the gene of the transmembrane subunit of lymphotoxin]. PMID- 7987232 TI - [Long-chained polyunsaturated fatty acids as modulators of the hydroosmotic action of vasopressin]. PMID- 7987233 TI - [Intrachromosomal mapping of the system E locus of blood groups in wild and domestic pigs]. PMID- 7987234 TI - [Formation of crystalline packing in reconstructed membranes from bacteriorhodopsin and egg phosphatidylcholine]. PMID- 7987235 TI - [Synthesis and study of properties in monolayers of potential immunomodulators based on modified glycolipopeptides]. PMID- 7987236 TI - [A myelopeptide, ameliorating the toxic effect of tumor cells on the functional activity of T-lymphocytes]. PMID- 7987237 TI - Structure of the polyglutamyl chain of tubulin: occurrence of alpha and gamma linkages between glutamyl units revealed by monoreactive polyclonal antibodies. AB - Polyglutamylation, a posttranslational modification which consists of the sequential addition of one to six glutamyl units in the carboxy-terminal domain of both tubulin subunits, is a major event in neurons. Its structure has been investigated by using monoreactive polyclonal antibodies directed against distinct glutamylation motifs, ie alpha- and gamma-linkages between glutamyl units. It is shown that, beside alpha-linkages previously characterized, gamma linkages also occur in glutamyl chains of brain tubulin. The co-existence of these two basic motifs leads to a conception of the polyglutamyl chain with a very sophisticated structure which could, through its complexity, help the microtubule to reach its structure and fulfil its functions. PMID- 7987238 TI - The orientation of primary cilia during the wound response in 3Y1 cells. AB - The behavior of the primary cilia of 3Y1 cells in the interphase was investigated by indirect immunofluorescence microscopy and transmission electron microscopy, using an antibody for tubulin. At 4.5 h after scraping a part of a confluent cell sheet, the primary cilia of cells facing the wound were located predominantly forward of the nucleus on the wounded side, and were oriented in the direction of the leading lamellae. Cytoplasmic microtubules (MTs), emanating from around the base of the cilia, were well developed in the leading lamellae on the wounded side. On the other hand, in the cells of an unperturbed area away from the wounded edge, the primary cilia remained randomly distributed near the nucleus. The position and a certain well-defined orientation of a pair of centrioles seem to play an important role for the development of cytoplasmic MTs, and consequently the orientation of the centrioles is controlled by the primary cilia. PMID- 7987239 TI - Protein kinase C (PKC) level is increased in PC12 cells overexpressing transfected liver-type phosphofructokinase. AB - PC12 cells which overexpress transfected liver-type phosphofructokinase (PFKL) have previously been described as a model system for PFKL overexpression in Down's syndrome and have been shown to perform glycolysis at enhanced rates. Here we report that levels of protein kinase C (PKC) in PC12-PFKL cells were almost doubled, as estimated from in vitro activity and phorbol ester binding experiments and from an increase found in PKC-alpha mRNA levels. Most of the added PKC was found to be associated with the cellular membrane while the cytoplasmic levels of PKC were barely increased. The steady-state levels of 1,2 sn-diacylglycerol in PC12-PFKL cells were found to be unaltered, suggesting that enhanced glycolysis in these cells did not influence PKC by altering the amounts of this compound. PFKL is one of several genes known to be overexpressed in Down's syndrome. Upregulation of PKC due to PFKL overexpression could result in widespread disturbances of gene expression and play a part in causing some of the many symptoms of the disease. PMID- 7987240 TI - Effects of retinoic acid metabolites on proliferation and differentiation of the clonal rhabdomyosarcoma cell line BA-HAN-1C. AB - The clonal rat rhabdomyosarcoma cell line BA-HAN-1C is composed of proliferating mononuclear cells, some of which spontaneously fuse to terminally differentiated myotube-like giant cells. This cell line has been shown to be susceptible to differentiation induction with all-trans retinoic acid (RA). Since it is still unknown whether exclusively all-trans RA itself or also its metabolites can act as inductive compounds in our cell line, we exposed BA-HAN-1C cells to the metabolites 4-hydroxy RA, 4-oxo RA and 5,6-epoxy RA. Exposure to these RA metabolites resulted in a significant inhibition of proliferation (P < 0.001) and induction of cellular differentiation, as evidenced by a significant increase in the number of myotube-like giant cells (P < 0.05) and a significant increase in creatine kinase activity (P < 0.05). However, differences in the inductive potency of these RA metabolites became apparent. Furthermore, RA metabolites exhibited a significantly weaker (P < 0.05) inductive activity when compared to all-trans RA. Summarizing our results we could demonstrate that the endogenous metabolites 4-hydroxy RA, 4-oxo RA and 5,6-epoxy RA are not merely deactivated cellular excretion products of all-trans RA, but potent inducers of differentiation and inhibitors of proliferation, possibly contributing to the complex physiological actions of retinoic acid. PMID- 7987242 TI - Nuclear matrix involvement in sperm head structural organization. AB - In the sperm nuclei the DNA is packaged into a highly condensed form and is not organized into nucleosome and solenoid but is bound and stabilized mainly by the protamines that arrange the DNA in an almost crystalline state. As demonstrated for somatic cells, the sperm DNA has been reported to be organized in loop domains attached to the nuclear matrix structures. However, the possible role of the sperm head matrix in maintaining the loop organization in absence of a typical nucleosomal structures has not been fully elucidated. By using in situ nick translation at confocal and electron microscope level, we analyzed the organization of the DNA-protamine complex and its association with the sperm nuclear matrix. The data obtained indicate that the chromatin organization in sperm nuclei is maintained during the sperm condensation by means of interactions with the nuclear matrix at fixed sites. The fine structure of sperm nucleus and of sperm nuclear matrix, investigated on sections and replicas of freeze fractured specimens, suggests that the lamellar array, observed by freeze fracturing in the sperm nuclei, could depend on the inner matrix which presents a regular organization of globular structures possibly involved in the maintenance of chromatin domains in highly condensed sperm nuclei also. PMID- 7987241 TI - The proliferating cell marker monoclonal antibody Ki-67 recognizes specific antigens associated with the nuclear envelope of the early Drosophila embryo. AB - Immunofluorescence and immunoelectron microscopy indicated that the antibody raised against the nuclear antigen Ki-67 of mammalian cells recognized antigenic determinants of early Drosophila embryos, localized on the outside of the nuclear envelope. Hence, the nuclear envelope of Drosophila appears to share a similar epitope with the chromosome scaffold of mitotic mammalian cells. With the progression of mitosis the antigen persisted around the mitotic spindle region and was also found in the pole regions at metaphase and anaphase. The antibody also stained the equatorial regions of the spindles from anaphase to late telophase. The antibody may therefore be used as a biochemical marker of the nuclear envelope for studying nuclear membrane biogenesis and behavior during the mitotic divisions of the Drosophila embryo. PMID- 7987243 TI - Advantages of the scanning ion microscopy for mapping halogen corticoids in normal and transformed cells in culture. AB - The intra-cellular distribution of eight halogen glucocorticoids was investigated by ion microscopy in two cellular varieties of cultured non-cancer cells (fibroblast 3T3) and cancer cells (human breast tumor cells MCF-7). Two types of ion microscopy helped to determine this distribution, a direct imaging ion microscope (SMI 300) with low spatial resolution, and a scanning ion microscope (IMS4F), featuring high resolution, serving to obtain maps representing the intra cellular distribution of the fluorine elements and drugs present in these monolayer cultured cells. The fluorine images representative of the drugs containing fluorine showed that these drugs are essentially concentrated in the cell nuclei. In these nuclei, the distribution of these drugs is different from that of heterochromatin and of the nucleolus. PMID- 7987245 TI - Application of spheroid culture to human hepatocytes and maintenance of their differentiation. AB - Human hepatocytes cultured with a hormonally defined medium on non-adherent poly (2-hydroxyethyl methacrylate)-coated surface were able to form spheroids. The maintenance of liver-specific functions was assessed by following secretion of albumin, transferrin and alpha 1-antitrypsin that were still detectable after 4 months of spheroidal culture. Moreover, cytochrome P-450 IA was induced by methylcholanthrene for up to 2 weeks. This cell system is very promising for long term in vitro studies of human hepatocyte functions. PMID- 7987244 TI - Galectin-3 mRNA level depends on transformation phenotype in ras-transformed NIH 3T3 cells. AB - The increase in galectin-3 lectin content observed in tumours or in in vitro transformed cells suggests that this lectin is important in the transformation process. In the present study, we investigated the mRNA expression level of the galectin-3, galectin-1 and macrophage mannose receptor in normal and ras transformed NIH 3T3 cells in relation to their transformation state. The galectin 3 mRNA content in ras-transformed cells is increased in fully transformed cells, with a maximum in ras-transformed cells that have lost their growth anchorage dependence. Under the same conditions, the galectin-1 mRNA level which was high in normal cells, increased slightly in transformed cells. The mRNA for the macrophage mannose receptor was not detected in 3T3 cells or in their ras transformed counterparts. PMID- 7987246 TI - A SEM analysis of DMSO treated hydra polyps. AB - Scanning electron microscopy revealed that exposure of hydra polyps to DMSO at concentrations used for permeabilizing tissue results in striking changes in epithelial cell morphology. Epithelial cells from treated polyps rounded up in shape and formed numerous large blebs at the cell surface. Along the borders of epithelial cells numerous small projections became detectable. The DMSO-induced changes at the cell surface corresponded to drastic changes in the intracellular organization. No evidence could be found for DMSO induced opening of cell junctions and/or opening of the interstitial space. The results demonstrate that DMSO affects the morphology and intracellular organization of hydra epithelial cells. Thus, caution is necessary in interpreting cell behavior in DMSO treated tissue. PMID- 7987248 TI - Reduction of cumulative body weight gain and adipose tissue mass in obese mice: response to chronic treatment with synthetic hGH 177-191 peptide. AB - The effects of long-term treatment of C57BL/6J (ob/ob) mice with a synthetic carboxylterminal sequence of human growth hormone, hGH 177-191, were investigated. Results indicate that the hGH 177-191 reduced the cumulative body weight gain, and decreased the adipose tissue mass. The lipogenesis in adipose tissues was significantly inhibited by the treatment with hGH 177-191. These findings support the suggestion that hGH 177-191 is the functional domain of hGH for the antilipogenic actions of the intact hormone both in vivo and in vitro. The hGH 177-191 peptide has the potential to be an effective compound for the treatment of human obesity and for the improvement of meat qualities in farm animals. PMID- 7987247 TI - Comparative effects of dietary corn, fish and Krill oils on intestinal glycosylation. AB - Antarctic Krill is considered as a valuable protein resource for animal and human nutrition. Due to the high content of long chain polyunsaturated fatty acids of the n-3 family, Krill consumption could be also interesting in cardiovascular diseases. In the search for the demonstration of the absence of toxicity of Krill, we studied the effect of Krill oil, as compared to fish and corn oil, on the rat intestinal fucosylation process at weaning, a very sensitive model of the influence of nutritional factors. Krill oil containing diets were very well tolerated as compared to other currently used oils and induced only slight modification in fucose and mannose proportions in intestinal glycoprotein sugars. These modifications were not reflected in the enzymatic activities involved in the fucosylation pathway. These results confirm the harmlessness of Krill derived products and their possible use in human nutrition. PMID- 7987249 TI - How to determine control of growth rate in a chemostat. Using metabolic control analysis to resolve the paradox. AB - The chemostat makes it possible to study microbial physiology at steady state. However, because growth rate in a chemostat is set by the experimenter, it seems impossible to employ the chemostat to study the control of microbial growth by processes within the microorganism. In this paper we show how, paradoxically, one can determine control of growth rate, of growth yield and of other fluxes in a chemostat. We develop metabolic control analysis for the chemostat. This analysis does not depend on the particular way in which specific growth rate varies with the concentration of the growth limiting substrate. PMID- 7987250 TI - Presence of a mitochondrial DNA deletion in fetal and adult bovine cardiac tissue. AB - A deletion of about 5.3 kilobases has been detected in the mitochondrial DNA of bovine cardiac tissue. This deletion appears to be somatic in origin given its sporadic presence in the various heart compartments examined. Cardiac tissue derived from developmental stages including fetal, early and older adult animals harbored this mutation with increased levels (100-1000 fold) found in older adults. The deleted region of the mitochondrial genome maps to relatively the same area (deleting ATPase6, COXIII, ND2, ND4 and a portion of ND5) as the common 5 kb deletion reported in humans, but its presence in fetal tissue, as well as its decreased age dependence distinguish it relative to the reported human deletion. PMID- 7987251 TI - A model demonstrating different interactions of human coagulation factor XII (Hageman factor) with the surface at physiological and lower pH. AB - The surface binding activity of human coagulation factor XII is independent of pH while its proteolytic breakdown decreases considerably on lowering the pH (Samuel, M. and Villanueva, G.B. (1992) Biophysical J. 61, 1895). In the present study we showed that the amidolytic activity of factor XII in the presence of a soluble surface, dextran sulfate (DS500; Mr 500,000) decreases on lowering the pH. Electrophoretic and ultraviolet difference spectral studies indicate that factor XII binding stoichiometry to DS500 is reduced to half at pH 5.3 when compared to that at pH 7.4. A model is presented to show the different interactions of factor XII with DS500 which explains its well known stability at low pH. PMID- 7987252 TI - Biodynamic study of americium-241 accumulation in the cytosol of the hepatopancreas of the lobster Homarus gammarus. AB - In the lobster, most of the radionuclides ingested with contaminated food are concentrated in the digestive gland. Americium-241 accumulation in the hepatopancreas of the lobster was studied during the digestive cycle. Fractionations of cytosols at different times after ingestion of radioactive preys were performed by gel permeation chromatography to determine the distribution of 241Am in the different macromolecular components. 241Am was associated with ferritin during the whole digestive cycle. This observation suggests a correlation between 241Am distribution pathways and iron metabolism. The distribution of 241Am present in the other cytosolic proteins followed two major steps of accumulation which may be correlated to the evolution of the two main cellular types playing an important role in the digestive cycle (B and R type cells). PMID- 7987253 TI - Appearance of homogeneous smectic multilamellar microenvironments in biomembranes undergoing superoxide-initiated lipid peroxidation: lipid-dienyl radical accumulation and fluidity management in lipid bilayers. AB - Erythrocyte ghosts were exposed to various levels of oxyradical shock in order to identify the extent of accumulation of peroxidative intermediates. Malondialdehyde reacting end products were the same in all different models. But, the accumulation of dienyl radical species increased with higher intensity of oxyradical shock. These dienyl radicals may rearrange to create a homogeneous smectic multilamellar microenvironment which may be more fluid in terms of the molecular dynamics. PMID- 7987254 TI - Phorbol ester-, but not ligand-mediated activation of protein kinase C increases angiotensin binding to rat intestinal epithelial (RIE-1) cells. AB - Whereas direct activation of protein kinase C (PKC) by the phorbol ester, 12-O tetradecanoyl-phorbol-13-acetate (TPA) increased the subsequent binding of 125I labelled angiotensin II (125I-AII; 0.5 nM) to RIE-1 cells, ligand-mediated activation of the kinase via angiotensin II (AII), which activates the phosphoinositide (PI) pathway in these cells, had no effect. The apparent inability of AII to increase 125I-AII binding is unlikely to result from simultaneous, but opposing actions of AII on angiotensin receptor number and affinity since the peptide also had no effect on the saturation binding of 125I AII (10 nM) to the cells. Since 125I-AII binding was unaffected both by AII pretreatment in PKC-depleted cells, and by the calcium ionophore, ionomycin, in PKC-replete cells, an attenuating action of AII (opposing any PKC-mediated increase) on 125I-AII binding mediated via the calcium limb of the PI pathway is also unlikely. Instead, the contrasting effects of AII and TPA on 125I-AII binding to RIE-1 cells appear to relate to the degree of PKC activation elicited by each agent. PMID- 7987255 TI - Repulsive contribution of surface sialic acid residues to cell adhesion to substratum. AB - Roles of surface sialic acid residues in cell adhesion to substratum were investigated in model systems to clarify their contribution to intercellular interactions. Treatment of cells of a fibroblastic cell line, Swiss 3T3, an epithelial cell line, TES-1, and a T lymphoma cell line, BW5147, with a sialylated oligosaccharide binding lectin enhanced adhesion to plastic plates irrespective of the cell lineage. This enhancement was inhibited by the addition of sialyl lactose. Digestion of the cells with sialidase or endoglycoceramidase also augmented adhesion. On the other hand, adhesion was reduced by pre-coating plastic plates with gangliosides but not with desialylated gangliosides. These findings suggest that sialic acid residues exposed to cell surfaces negatively regulate cell adhesiveness. PMID- 7987256 TI - NMR study of lipoic acid binding to bovine serum albumin. AB - Evidence for the binding of lipoic (LA) and dihydrolipoic (DHLA) acid to bovine serum albumin (BSA) was sought as a feature for understanding the mechanism of their antioxidant activity and prevention of glycation. Experiments were performed by 1H high resolution NMR. The average binding ratio of LA, DHLA and tetranor LA to BSA were 10 +/- 2, 7.9 +/- 2 and 1.8 +/- 0.4 mol/mol BSA respectively. In this row the number of bound molecules lessens with the decrease of their hydrophobic interactions that correlates with their protective activity. Octanoic acid, the closest analog of lipoate, had a binding ratio of 4.7 +/- 0.5 mol. Lipoic acid was able to replace bound octanoic acid which points out that lipoate occupies the same binding site on BSA. Lipoate had no binding to low density lipoproteins extracted from human plasma which corresponds to its low protection of LDL against glycosylation and oxidative modification. This study indicates that lipoic acid molecules experience strong hydrophobic attraction and binding to BSA which is important part of lipoate protective mechanism. PMID- 7987257 TI - Class pi glutathione S-transferase: Meisenheimer complex formation. AB - The enzyme-catalysed formation of the dead-end Meisenheimer complex, 1-(S glutathionyl)-2,4,6-trinitrocyclohexadienate, between glutathione and 1,3,5 trinitrobenzene by two class pi glutathione S-transferases was studied under equilibrium conditions. The apparent formation constant of the complex at pH6.5, is 1.21 x 10(3) M-1 and 1.47 x 10(3) M-1 for isoenzyme pGSTP1-1 from porcine lung and hGSTP1-1 the human recombinant orthologue, respectively. These values are about 40- to 50-times larger than that determined for the nonenzymatic reaction in solution. Competitive inhibitors in the form of glutathione analogues that bind the G-site (glutathione sulphonate) or both the G-site and the H-site (S hexylglutathione) regions of the active site markedly diminish complex formation. Comparison of kinetic data for glutathione S-transferase isoenzymes from the pi and mu gene classes suggests that the catalytic efficiencies for nucleophilic aromatic substitution reactions correspond with the ability of the enzyme's active site to stabilise the Meisenheimer complex. Formation of the red-coloured complex in orthorhombic crystals of pGSTP1-1 demonstrated that the crystallized protein retains its catalytically functional conformation in the crystal lattice. PMID- 7987258 TI - Catalytic properties of carbonyl reductase from rabbit liver for analogs of acetohexamide and 4-acetylpyridine. AB - A correlation was observed between the values of specificity constant (kcat/Km) of carbonyl reductase from rabbit liver for acetohexamide analogs and their partition coefficients. This result indicates that the hydrophobicity in straight chain alkyl groups of acetohexamide analogs plays an important role in the catalytic activity and substrate-binding capacity of the enzyme. Furthermore, the double logarithmic plots of kcat/Km values of the enzyme for 4-acetylpyridine analogs with a straight-chain alkyl group up to five carbon atoms against their partition coefficients gave a straight line. On the other hand, the plots for 4 acetylpyridine analogs with a straight-chain alkyl group over five carbon atoms and with a branched-chain alkyl group were away from the straight line. It is reasonable to postulate that a hydrophobic pocket is located in the substrate binding domain of the enzyme. PMID- 7987259 TI - Accurate transcription initiation by RNA polymerase II from Candida utilis. AB - An in vitro transcription system from Candida utilis is described. The template used is a hybrid plasmid containing Saccharomyces cerevisiae CYC1 promoter linked to a synthetic 377-bp G-minus casette (1). In vitro transcriptions are carried out in the presence of RNase. T1. Under these conditions only the transcripts that are resistant to RNase T1 accumulate. Using this protocol, it has been shown that in the absence of cytosolic factors RNA polymerase II (pol II) from C. utilis initiated RNA synthesis randomly. But both C. utilis and S. cerevisiae cell-free extracts could direct pol II from C. utilis to initiate transcription accurately. Results also indicated that the general transcription factors are functionally interchangeable between S. cerevisiae and C. utilis. PMID- 7987261 TI - Expression cloning, purification and characterization of a beta-1,4-mannanase from Aspergillus aculeatus. AB - A cDNA library from the filamentous fungus Aspergillus aculeatus was constructed in the yeast expression vector pYES2.0 and used to isolate 57 full length cDNA's encoding beta-1,4-mannanase by expression in S. cerevisiae. The positive clones were identified on agar plates containing 0.2% azurine dyed cross-linked mannan by the formation of blue halos around the colonies. All clones represented transcripts of the same mannanase gene (man1). The gene was sub-cloned into an Aspergillus expression vector and transformed into Aspergillus oryzae for overexpression and purification of the enzyme. The recombinant enzyme had a molecular weight of 45 kDa, an isoelectric point of pH 4.5, a pH optimum of pH 5.0 and a temperature optimum of 60-70 degrees. PMID- 7987260 TI - Transfer RNA binding to 80S ribosomes from yeast: evidence for three sites. AB - The number of tRNA binding sites in 80S ribosomes from Saccharomyces cerevisiae was assessed by means of tRNA saturation and translocation experiments. In the absence of cognate mRNA yeast ribosomes could bind 0.6 [32P]tRNA(Phe) per 80S while poly(U) programmed ribosomes accepted up to 1.7 tRNA(Phe) molecules per 80S or 0.5 molecules of Ac[14C]Phe-tRNA(Phe) per 80S. Compared with the known features of E. coli ribosomes these binding values indicated both the presence of three tRNA binding sites and the validity of the exclusion principle for peptidyl tRNA binding to yeast ribosomes. Upon EF-2 dependent translocation of a complex containing deacyl-tRNA in the P-site and AcPHe-tRNA in the A-site, the deacylated tRNA does not leave the ribosome quantitatively. This observation suggests the presence of an E site in 80S ribosomes which is functionally equivalent to the one previously characterized in prokaryotic systems. PMID- 7987262 TI - Effects of glucose, ethanol, Hg(II) and Cu(II) on almond beta-glucosidase. AB - The kinetic parameters of almond beta-glucosidase (beta-D-glucoside glucohydrolase; EC 3.2.1.21), using pNGP as substrate were kM = 2.24 +/- 0.11 mM and Vmax 588 +/- 25.1 U/mg protein. Only Hg(II) and Cu(II) showed irreversible inactivation of the enzyme. However, when these metals were present in the reaction system the inhibition effects were consistent with a mixed-type inhibition pattern (Cu(II) ki: 5.08 mM and Hg(II) ki: 0.07 mM). The glucose kinetic effect was also consistent with a mixed-type inhibition (ki = 406 mM) pattern with pNGP as varied substrate. Ethanol displayed the kinetic pattern of competitive inhibition (ki = 640 mM). PMID- 7987264 TI - Inhibition of ADP-induced human platelet aggregation by a new class of soluble guanylate cyclase activators capable of nitric oxide generation. AB - Diazetidine-di-N-oxide derivatives have been found capable of the nonenzymatic generation of nitric oxide by a principally new mechanism of nitric oxide splitting at physiological pH values. The effect of the synthesized compounds on human platelet soluble guanylate cyclase activity and ADP-induced human platelets aggregation were studied. Four of 7 derivatives studied exhibited a distinct correlation between the intensity of platelet guanylate cyclase activation, inhibition of platelets aggregation and acceleration of their disaggregation. The NO-dependent mechanism of guanylate cyclase activation and intraplatelet cGMP accumulation are suggested to be responsible for antiaggregatory/disaggregatory properties of the compounds used. Data presented allow us to regard 1,2 diazetidine-di-N-oxide derivatives as antiaggregatory agents of a new class. PMID- 7987263 TI - Chemical modification of lysyl residues of Rhodotorula gracilis D-amino acid oxidase. AB - D-amino acid oxidase from the yeast Rhodotorula gracilis is irreversibly inactivated by reaction with TNBS with complete inactivation accompanied by covalent modification of lysine residues of the protein. The inactivation was biphasic, the fast phase being dependent on TNBS concentration and completed in less than 1 minute. The competitive inhibitor benzoate afforded partial protection against inactivation during the fast phase of the process, with no effect on the slow phase. The pH curve of inactivation (slow phase) indicates the involvement of a residue(s) with a pK of 8.2. Amino acid analyses showed that in the fast phase of inactivation 1.6 lysine residues were modified, whereas up to 13 lysine residues were modified in the slow phase of inactivation. Our data show that TNBS behaves as an active site-directed reagent in yeast D-amino acid oxidase and they suggest the presence of at least one essential lysyl residue at or near the active site. PMID- 7987266 TI - Induction of stearoyl-CoA desaturase 2 gene expression correlates with fatty acid changes in phosphatidylcholine. AB - Chronic exposure of BW5147 cells to arachidonic acid results in a complete inhibition of stearoyl-CoA desaturase 2 gene expression. Following removal of the fatty acid, gene transcription increased with a kinetic profile similar to the observed increases in both stearoyl-CoA desaturase 2 mRNA and unsaturated fatty acid synthesis. During the time period when stearoyl-CoA desaturase 2 transcription and unsaturated fatty acid synthesis increased (6-12 h), there was only a minimal depletion (approximately 2%) of the total phospholipid arachidonic acid-content. By contrast, during the same period there was a specific depletion of arachidonic acid from phosphatidylcholine, but the proportion of arachidonic acid in other phospholipid species did not change. Thus, changes in the fatty acid content of phosphatidylcholine may be of particular importance in the genetic regulation of endogenous lipid synthesis. PMID- 7987265 TI - Intracellular Ca2+ store from rabbit brain: kinetic aspects of Ca(2+)-stimulated ATPase. AB - The endoplasmic reticulum of the rabbit brain manifests low but distinguishable Ca(2+)-stimulated ATPase activity with some functional peculiarities compared to the muscle isoforms. The activity is highly sensitive to the presence of detergents and optimal activatory concentration was shown to be close to the critical micellar concentration. Kinetic properties, such as (i) activation by low (K0.5 = 0.45 microM) and inhibition by high (more than 100 microM) concentration of calcium, (ii) biphasic activation with ATP and (iii) inhibition by vanadate clearly showed that the protein of Ca(2+)-ATPase is endowed with properties typical of the family of sarco/endoplasmic reticulum calcium pumps. PMID- 7987267 TI - Combined psychological and prosthetic management of tinnitus: a cross-sectional study of patients with severe tinnitus. AB - A consecutive clinical sample of 154 highly selected patients with severe problems due to tinnitus have been treated within a programme combining psychological and prosthetic approaches. The therapy works within the framework of existential psychology. The programme was evaluated by a postal questionnaire. Pre- and post-intervention comparisons of self-rated tinnitus loudness, major problems in getting to sleep and concentration showed significant improvement in all three domains. The patients greatly appreciated the programme and benefited from information on coping strategies, use of natural masking sounds and from reassurance about lack of serious pathology and prognosis. After intervention the patients were more active in sharing information about tinnitus with key persons, although the consequence in terms of greater empathy was discouraging. Two-thirds of the patients fitted with instruments as part of the programme still had their devices at follow-up. The intervention package has been evaluated as a whole, and therefore it is not possible to separate which part of the intervention each patient benefited from most. It is concluded that improvements in the lives of patients with severe problems due to tinnitus can be achieved within a management programme of this kind. The patients were divided into three severity groups according to pre-intervention impact of tinnitus upon life. Post-intervention evaluation showed that the two more afflicted groups had significantly greater benefit from the intervention in terms of self-rated tinnitus loudness and major problems in getting to sleep compared to the less afflicted group. A small subgroup of younger male political refugees was found less suitable for this type of programme. Both clinically and in the research area it is essential to specify the severity of tinnitus, and there is an urgent need to reach international consensus concerning this issue. PMID- 7987268 TI - Is the test of medial efferent system function a relevant investigation in tinnitus? AB - The present results are drawn from preliminary observations made in 28 patients suffering from unilateral, permanent, non-pulsatile tinnitus, who were systematically submitted to an investigation of their otoacoustic emissions in both ears. Spontaneous otoemissions (SOAE) were carefully looked for, before recording of transient evoked otoemissions (TEOAE). The effectiveness of the medial olivo-cochlear efferent system (MOC) was also tested. The comparison between TEOAE input/output curves obtained with and without contralateral stimulation allowed a global assessment of the functioning of MOC. Additional information relating to the MOC functioning at the precise frequency of tinnitus and/or around it, was available from the comparison of analogous curves obtained using distortion product otoacoustic emissions (DPOAE) instead of TEOAEs. The results show that: (1) when the amplitude of otoacoustic emissions differs between the two ears, the tinnitus is generally lateralized on the side where amplitude was the lowest, which seems to be related to a greater hearing loss; (2) no general law concerning tinnitus can be drawn from the global testing of MOC functioning; the only result is that the slope of TEOAE input/output function appears as a deciding factor for efficiency of MOC, the least efficiency almost always occurring on the side where the slope is greater, and (3) even in the case of proved global effectiveness of MOC activation, there is, at least in the vicinity and in at least one ear, a part of the cochlea where its functioning is altered. A better comprehension of the mechanisms underlying this symptom will probably come from exhaustive exploration of individual cases rather than a rougher investigation of large samples in which different aetiologies are likely to be mixed. PMID- 7987269 TI - Validation of parameters for assessing Obscure Auditory Dysfunction--robustness of determinants of OAD status across samples and test methods. AB - About 5% of those presenting at an ENT clinic with ear or hearing complaints are found to have normal pure-tone thresholds. Many of this group complain specifically of difficulties understanding speech in background noise. We have termed this complaint 'Obscure Auditory Dysfunction' (OAD). Previous research on OAD (Saunders and Haggard, 1992) on a sample of 50 patients and 50 matched controls showed that 83% of the deviance (binary variance) in membership of group (OAD/control) could be explained by four variables, with three underlying factors. These four variables are performance threshold in noise for speech; discrepancy between this and a self-adjusted signal-to-noise ratio value (i.e. a measure of auditory confidence); dichotic listening performance; and performance on a psychoacoustic test, the threshold for detecting a tone in a spectrally notched noise. This paper reports a study on a further 59 new OAD patients and 64 unmatched controls, using the tests in the form present in the test package, plus certain others. For routine practice, slightly differing implementations of the auditory test techniques were used. Compared to the earlier sample, the new sample had poorer measures of speech reception threshold in noise and they considered themselves more handicapped by their OAD state; however there was no significant difference between the two samples on the other performance variables. Overall, the results demonstrate the robustness of the conclusions reached from the previous study, as the test-variable determinants of OAD status (i.e. case-control differences) were similar. The items on the OAD interview questionnaire which had shown significant differences between OADs and controls were also similar for the two OAD samples, giving a consistent picture of patient profile. These were: difficulties learning to read or write as a child (which relates to dichotic listening scores); adult ear problems; and tinnitus (which relate to the psychoacoustic scores). This necessary replication confirms the validity of the three-factor model of OAD status and the utility of the clinical test package based upon it. PMID- 7987270 TI - A review of computerized electronystagmography technology. AB - Analysis of nystagmus using manual methods is time consuming, reliant on considerable experience and subject to observer bias. Like many electrophysiological responses, nystagmus waveforms are suited to acquisition and analysis by digital computer techniques. Development of computerized eye movement analysis procedures commenced in the late 1960s. Initially programs were mostly researched-based with the data often acquired on FM tape recorders and evaluated on mini-computers. As computer technology evolved and equipment prices decreased, development of portable software and hardware for use in general clinical assessment became feasible. The development of computer programs for the acquisition and analysis of eye movements is described and the limitations of analysis procedures discussed. PMID- 7987271 TI - Feasibility of otoacoustic emission detection followed by ABR as a universal neonatal screening test for hearing impairment. AB - The feasibility of attempting a two-stage universal screening test for auditory impairment was assessed at a large district maternity hospital. The first stage was measurement of otoacoustic emissions using the Programmable Otoacoustic Emission Measurement System. Those failing the first stage proceeded to automated analysis of auditory brainsteam responses. A single tester working for 6 h on 6 days per week attempted to test all babies born between the hours of midday and midnight for 2 weeks and then all babies born between midnight and midday for a further 2 weeks. Of 217 babies born during the study periods, one infant died and three were still receiving intensive care at the end of the study. Of the remaining 213 infants, auditory testing was undertaken in 201 infants (94%). Eight infants (4%) who failed the first stage of the screening test did not undergo the second stage. Of those 193 infants completing the screen, one (0.5%) failed the screen unilaterally. There were no bilateral failures. Three testers, working two and a half whole-time equivalents, should be adequate to achieve a coverage of 90% and a specificity of 99% for this screen in this clinical setting. PMID- 7987272 TI - Maintaining the Ineraid cochlear implant. AB - Managing a patient with acquired profound deafness with a cochlear implant involves a lifetime commitment to rehabilitation and also to maintaining the device in a functioning condition. This paper describes the Cambridge experience of maintaining the Ineraid cochlear implant in a series of 25 patients over a 4 year period. On average, maintenance (repair of replacement) of components was required every 2.3 months of implant use, although some minor variations were noted between patients, and between component type. This rate of failure is sufficient to cause an Implant Centre to consider provision for repairs and holding of spare stock. It should be remembered that each breakdown returns the patient to a deafened state, albeit temporarily, but this can cause significant distress. PMID- 7987273 TI - Hearing disability in music and non-music students. PMID- 7987274 TI - [Molecular genetics of thyroid diseases]. AB - Molecular cloning of the genes implicated in the synthesis of thyroid hormones and in the control of thyroid growth and function has led to the identification of mutations responsible for hereditary thyroid diseases (congenital hypo- and hyperthyroidism) and for hyperfunctional thyroid adenomas. PMID- 7987275 TI - [Genome diagnosis in domestic animals]. AB - Different contributions to the development and applications of genomic diagnosis methods in domestic animals are reported. DNA fingerprints were used to solve parentage disputes in different species, and to reveal leucochimerism in bovine dizygotic twins. In cattle, an embryo sexing method and a freemartinism diagnosis assay were also developed. The search for molecular markers of the MH (muscular hypertrophy) and R (rouan) bovine genes is described. Prion protein gene polymorphisms are investigated in the framework of a research on the genetics of bovine spongiform encephalopathies. The mutation responsible for the autosomal recessive lethal condition BLAD (bovine leucocyte adhesion deficiency) in Holstein cattle is found in our country, and the carries can be detected by a molecular method. The mutation responsible for the halothane sensitivity in pig can also be detected, what is done to control efficiently the introgression of the stress resistance allele in a Pietrain strain. PMID- 7987276 TI - [Drugs and lactation]. AB - In that book, the authors make a detailed review of drug transfer into breast milk. The first chapter provides the reader with a useful reminder of basic pharmacokinetics principles. Milk transfer of each individual drug is then discussed: based on the literature data available, an estimation is made of the total amount of drug transferred into milk during a treatment period of one day. Taking into account the doses recommended in neonatology and pediatrics, a conclusion is drawn regarding the use of the drug during the lactation period. The aim of the book is to help physicians, pharmacists, nurses and other health professionals in the prescription of drugs to breastfeeding mothers. PMID- 7987277 TI - [History of the history of medicine and its significance. Trends in a discipline in transformation]. AB - This paper gives an account of the new orientations in history of Medicine, of its opening up, and of the new pluridisciplinary approach it intrinsically requires. It examines the past of the history of Medicine. This discipline, born during the 18th century, was at the beginning indistinguishable from Medicine in itself. This first period, that of the myth of the founder, was followed, during the 19th century, by a positivist historiography, inspired by the myth of the precursor. Now, released from this double historiographical myth, present history of Medicine attempts to understand the past of Medicine, considering a set of factors that are together scientific, social and cultural. PMID- 7987278 TI - [Localization and role of cholecystokinin and its receptors in the functional organization of the basal ganglia]. AB - In human, cholecystokinin-immunoreactive nerve fibres are abundantly distributed in the ventral striatum and in other regions of the basal ganglia interconnected with the limbic system. This suggests that this neuropeptide is involved in the initiation of movements following emotional stimuli. The demonstration of an extended cholecystokinin expression in cortico-, thalamo-, and nigrostriatal pathways using in situ hybridization indicates that this neuromodulator may have some important functions either in motor, cognitive or limbic systems. In addition, disruption of the nigrostriatal dopaminergic pathway induces the expression of cholecystokinin in the striatal neurons. This new example of functional plasticity suggests that dopamine exerts a negative tonus on cholecystokinin expression. Finally, cholecystokinin expression is increased in meso-limbic and nigrostriatal dopaminergic neurons of schizophrenic patients. PMID- 7987279 TI - [Role and function of the National Consulting Committee of Ethics in France]. PMID- 7987280 TI - [Committee of Ethics and Legislation]. PMID- 7987281 TI - [Ethical hazards in the search for new drugs]. PMID- 7987282 TI - [The convention of bioethics]. PMID- 7987284 TI - [Brain and spinal cord grafts. Ethical aspects]. PMID- 7987283 TI - [Gene therapy: facts and hopes]. PMID- 7987286 TI - [Academic eulogy for Professor M. Appelmans, titular member and former president]. PMID- 7987285 TI - [Bioethics, biomedicine and economic factors]. PMID- 7987287 TI - [Distribution and function of a new hormone: parathyroid hormone-related peptide (PTHrP)]. AB - Several research groups have identified a "parathyroid hormone related peptide" (PTHrP) in tumors of patients presenting with the hypercalcemia of malignancy. The N-terminal domain of this peptide has a high degree of homology with that of the parathyroid hormone (PTH) and shares the PTH biological activities. PTHrP has later been identified in several foetal and adult normal tissues: for instance, it is expressed and secreted by foetal parathyroid glands, and it plays an important role in placental calcium transport; it is also expressed in the uterus of pregnant rats; there it could have a paracrine action on myometer relaxation. We have shown that PTHrP is present in and released in culture by foetal rat long bones. The mRNA of PTHrP is expressed in the periosteal cells of these foetal bones. The local expression and secretion of PTHrP in bone suggests that this new peptide could have a local role in the regulation of bone remodeling and development. PMID- 7987288 TI - Post-coma disturbance and post-traumatic amnesia as nonlinear predictors of cognitive outcome following severe closed head injury: findings from the Westmead Head Injury Project. AB - This study sought to identify combinations of early neurological variables which best predict cognitive outcome 12 months after severe head injury. At the time of admission patients were assessed on seven neurological indices. Twelve months later a battery of neuropsychological tests examining recent memory functioning and speed of information processing was administered. Recent memory functioning was best predicted by a combination of post-coma disturbance (PCD; i.e. the duration of post-traumatic amnesia, PTA, minus the duration of coma) and presence of subarachnoid haemorrhage (multiple r = 0.54, p < 0.001). Speed of information processing was best predicted by the duration of PTA (r = 0.35, p < 0.01). However, these conclusions were based on square root transformation of PCD and PTA variables. The success of this transformation in assisting prediction confirms suggestions that the relationship between PTA and cognitive outcome is nonlinear. PMID- 7987289 TI - Maintenance and generalization of behaviours after treatment of persons with traumatic brain injury. AB - This review of behavioural research literature was conducted to determine if persons who have experienced a traumatic brain injury are able to maintain and generalize behaviours after training, and to identify formal programming strategies that might have been utilized to enhance maintenance and generalization. Studies reviewed included those that employed behavioural procedures to increase adaptive behaviours or reduce maladaptive behaviours and collected maintenance and generalization data. Results of the review indicate that persons who have experienced a traumatic brain injury have experienced successful response maintenance and generalization of community-referenced tasks. It is suggested that impaired memory does not keep persons from maintaining and generalizing such tasks, and that strategies to promote maintenance and generalization need to be included in behavioural programming. PMID- 7987290 TI - Event-related potential indices of visual attention following moderate to severe closed head injury. AB - Covert orientation of visual attention was studied in eight closed head injury (CHI) subjects who fixated warning cues and pressed a button at peripheral target onset. Directional cues (arrows) indicated the most probable (p = 0.8) side of target occurrence while neutral cues (crosses) gave no directional information. A NoGo cue (vertical bar) indicated no response was required. Compared to eight matched controls the CHI subjects displayed slowed processing of all cues (increased P2, N2 and P3 latencies). Also, evidence was found for very early impairment (increased P2 amplitude) in directing attention. Further, the CHI group did not show the normal attenuated CNV after NoGo signals, suggesting perseverative behaviour. Finally, the amplitude and latency of the P3 component (post-cue and post-target) approached normal as time since injury increased. PMID- 7987291 TI - Massive pulmonary embolization with cerebral tissue due to gunshot wound to the head. AB - Autopsy findings in a 22-year-old man who received a gunshot wound to the head and died at the scene are presented. Massive white-grey emboli were found in the pulmonary arteries, and these were identified as cerebral cortical or glial tissue by histological examination. It was thought that the momentary severe increase of intracranial pressure and simultaneous rupture of the superior sagittal sinus due to the kinetic energy of the bullet had caused the lacerated cerebral tissue to enter the blood stream. PMID- 7987292 TI - The role of caudate nucleus and corpus callosum atrophy in trauma-induced anterior horn dilation. AB - Day-of-injury computerized tomography (CT) scans were compared to post-injury (at least 6 weeks) magnetic resonance (MR) imaging of 30 traumatic brain-injured (TBI) patients. Scans were matched as closely as possible at the head of the caudate nucleus (CN), a grey matter structure, and the anterior horns (AH) of the lateral ventricle. The CN and AH surface areas and width of the corpus callosum (CC), a white-matter structure, were measured. Results demonstrated a non significant change in CN surface area, while AH showed a significant increase. CC showed a significant decrease in width. Lack of significant change in the CN, combined with a significant decrease in CC width, suggests that AH dilation is probably due to surrounding white as opposed to grey-matter atrophy. PMID- 7987294 TI - What's in a spot? PMID- 7987293 TI - Male pituitary-gonadal dysfunction following severe traumatic brain injury. AB - A prospective study was conducted to evaluate pituitary-gonadal function and correlated parameters in 21 adult males with severe traumatic brain injury during acute inpatient rehabilitation. Serum concentrations of testosterone, follicle stimulating hormone (FSH) and luteinizing hormone (LH) were measured within 1 week after the patient was transferred to the rehabilitation unit. Fourteen of 21 patients (67%) had abnormally low testosterone levels. One of 21 patients had a subnormal FSH level and one had a supranormal level. Three of 21 patients had subnormal LH levels and two had supranormal levels. There was no correlation between the severity of brain injury and the levels of testosterone, FSH or LH. The presence of increased intracranial pressure, hypoxia, skull fracture or abnormal CT findings had no significant influence on the levels of testosterone, FSH or LH. The high incidence of hypotestosteronaemia in survivors of severe traumatic brain injury is seemingly more related to accompanying physiological stressors rather than structural or neurochemical disruption of the hypothalamic pituitary-gonadal axis. Early identification is important relative to the potential neuromedical and rehabilitative consequences of prolonged hypotestosteronaemia in this patient population. PMID- 7987295 TI - Identity-by-descent and association mapping of a recessive gene for Hirschsprung disease on human chromosome 13q22. AB - Hirschsprung disease (HSCR) is a congenital disorder of unknown etiology characterized by the absence of enteric ganglia in the distal colon. We have ascertained a large, inbred, Mennonite kindred which demonstrates a high incidence of Hirschsprung disease (HSCR). Genealogical analysis of all kinship relationships identified a single common ancestral couple for all parents of affected offspring. Segregation analysis yielded a segregation ratio of 10.67% for males and 5.45% for females. We searched for locations of the gene(s) responsible for HSCR in this pedigree by genotyping three small multicase families and locating genomic regions demonstrating identity-by-descent followed by linkage disequilibrium analysis of 28 additional nuclear families. Based on this novel strategy, we report the mapping of a new locus for HSCR to chromosome 13q22. Nine microsatellite markers spanning 10 cM in this region were genotyped on thirty-one nuclear families. Significant nonrandom association was detected with alleles at markers D13S162, D13S160, D13S170, and AFM240zg9. In addition, our studies reveal preliminary evidence for a genetic modifier of HSCR in this kindred on chromosome 21q22. PMID- 7987296 TI - Dissecting the centromere of the human Y chromosome with cloned telomeric DNA. AB - We have used telomeric DNA to break the human Y chromosome within the centromeric array of alphoid satellite DNA and have created two derivative chromosomes; one consists of the short arm and 140 kb of alphoid DNA, the other consists of the long arm and 480 kb of alphoid DNA. Both segregate accurately at mitosis. It is known that there is no large scale sequence duplication around the alphoid DNA and so the simplest interpretation of our results is that the sequence responsible for accurate segregation is the alphoid DNA itself. Although the long arm acrocentric derivative segregates accurately it lags with respect to the other chromosomes in about 10% of anaphase cells and thus additional sequences may be required for orderly segregation. The short arm acrocentric chromosome is probably no larger than 12 Mb in size and thus our results also demonstrate that chromosomes of this size are capable of accurate segregation. PMID- 7987297 TI - Cloning and characterization of human and mouse homologs of the Drosophila calcium-activated potassium channel gene, slowpoke. AB - Potassium channels play important roles in a wide variety of physiological processes. Although several genes encoding voltage-activated potassium channels have been analyzed at the molecular level, no calcium-activated potassium channel gene has yet been characterized in humans. In an effort to provide the foundation for functional analysis of such polypeptides we report the cloning of mouse and human homologs of the Drosophila melanogaster calcium-activated potassium channel gene, slowpoke. Both the human and mouse genes encode polypeptides that have more than 50% amino acid identifies with their Drosophila counterpart. In addition, like the Drosophila slowpoke gene, both the mouse and human genes generate multiple transcripts by alternative splicing. The human gene maps to chromosome 10 based on the results of polymerase chain reaction analysis of genomic DNA from human-hamster hybrid cell lines. Because calcium-activated potassium channels participate in wide variety of cellular functions including neuromuscular communication, secretion and cellular immunity, their continued analysis promises to have broad biological and medical significance. PMID- 7987298 TI - Distribution of CENP-B boxes reflected in CREST centromere antigenic sites on long-range alpha-satellite DNA arrays of human chromosome 21. AB - The long-range organization of alphoid DNA arrays of human chromosome 21 was investigated using a mouse-human somatic cell hybrid. Two distinct long alphoid DNA arrays, the loci alpha 21-I and alpha 21-II, were identified in the centromere region of human chromosome 21. The alpha 21-I locus, composed of an array of 11 monomer repeat units (the 11 mer), was estimated to have a total length of 1.3 Mbp. CENP-B boxes, the binding sites of the centromere protein B (CENP-B), appeared in every other monomer unit in the 11 mer except for one place where two monomer units were repeated without any CENP-B box. The other locus, alpha 21-II, was found to be composed of alphoid subfamilies with low homology to the components of alpha 21-I locus. Five different alphoid clones presenting 32 monomer units in total were isolated from the alpha 21-II locus. Sequences of these monomer units diverged between 71-89% and no unit containing a CENP-B box was found. By analysis using two color FISH, the alpha 21-I was localized to the primary constriction, whereas the alpha 21-II site was located slightly to the short arm side. Furthermore, a combination of FISH and immunofluorescent staining indicated that the alpha 21-I site was co-localized and overlapped with the CREST centromere antigenic site on mitotic chromosomes and in interphase nuclei, while alpha 21-II was distributed broadly. Our data suggest that the locus alpha 21-I containing regularly spaced CENP-B boxes at high-frequency and the assembly site of the centromere antigens may be involved in common centromere function in both human and mouse cells. PMID- 7987299 TI - Somatic and MEN 2A de novo mutations identified in the RET proto-oncogene by screening of sporadic MTC:s. AB - Since germline mutations in the RET proto-oncogene (RET) predisposing to tumor development in Familial Medullary Thyroid Carcinoma (FMTC), Multiple endocrine neoplasia type 2A (MEN 2A), and Multiple endocrine neoplasia type 2B (MEN 2B) were reported, it has become possible to identify gene carriers with a very high degree of accuracy. Mutations in FMTC and MEN 2A exclusively affect cysteine residues in exon 10 and 11 of RET, whereas in MEN 2B codon 918 in exon 16 is involved. This latter mutation has also been described in a subset of apparently sporadic medullary thyroid carcinomas (MTC). Mutations in MEN 2B often occur as de novo germline mutations, whereas de novo mutations have not yet been described in FMTC or MEN 2A. We analyzed ten MTC:s and ten pheochromocytomas, all clinically judged to be sporadically occurring, by direct DNA sequencing of exons 10, 11, and 16 of RET. This analysis revealed a de novo germline mutation of codon 634 in exon 11 in a patient with MTC. In addition, somatic mutations of codon 918 in exon 16 in six of the remaining MTC:s were found. Interestingly, the presence of this somatic mutation was associated with a significantly less favorable clinical outcome. PMID- 7987300 TI - Linkage of 'pure' autosomal recessive familial spastic paraplegia to chromosome 8 markers and evidence of genetic locus heterogeneity. AB - 'Pure' familial spastic paraplegias (FSP) are neurodegenerative disorders that are clinically characterized by progressive spasticity of the lower limbs and are inherited as autosomal dominant (DFSP) or autosomal recessive (RFSP) traits. The primary defect in FSP is unknown. Genetic linkage analysis was applied to five RFSP families from Tunisia. In four of these five families tight linkage of the RFSP locus was established to the chromosome 8 markers, D8S260, D8S166, D8S285, PLAT, and D8S279. The RFSP locus in the fifth family was not linked to these markers which provided evidence of genetic locus heterogeneity in RFSP. Identification of the RFSP gene on chromosome 8 will help in understanding the genetic factors in motor neuron degeneration. PMID- 7987301 TI - Mutations in the type IV collagen alpha 3 (COL4A3) gene in autosomal recessive Alport syndrome. AB - A group of 22 unrelated patients with sporadic or non-X-linked Alport syndrome were screened for mutations in the non-collagenous domain of the type IV collagen alpha 3 (COL4A3) chain gene. The five 3'-exons of this gene, located on chromosome 2qter, were tested by single strand conformation polymorphism analysis and direct sequencing. One patient was heterozygous and another homozygous (Mochizuki et al., Nature Genetics, in press) for a deletion of five nucleotides. A third patient appeared to be a compound heterozygote for two different nonsense mutations. In two patients and the father of a deceased patient we found a heterozygous substitution of an evolutionary conserved leucine by proline. However, segregation data of the mutation and a COL4A3/COL4A4 CA-repeat marker in their families argued against a causative role of the missense mutation. Even drastic changes of strongly conserved amino acids, as in the Leu36Pro case, may not be significant. Autosomal recessive inheritance due to pathogenic COL4A3 mutations accounts for at least 13% of Alport syndrome cases in this sample. It is concluded that COL4A3 is a major gene in the genetically and clinically heterogeneous Alport syndrome. PMID- 7987302 TI - Released chromatin: linearized DNA for high resolution fluorescence in situ hybridization. AB - Free DNA was prepared from routinely harvested and fixed cells for high resolution FISH mapping using either a sodium hydroxide/ethanol mixture or 70% formamide. Hybridization signals from cosmid probes appeared as extended lines. The average length of signals on DNA prepared with sodium hydroxide was significantly greater than with formamide. A set of overlapping cosmids from the HLA class II region was used to determine how precisely the actual overlap or gap between probes can be calculated from the measured overlap or gap between their signals. Lengths of the probe signals and their known kilobase lengths were used as an internal ruler. The mean values calculated from the measured length from 30 or more signals for each probe pair showed remarkable conformity with the known kilobase lengths of their overlaps and gaps. Immediately adjacent probes could also be ordered on the released DNA. These simple procedures dramatically increase the speed with which relationships between probes can be determined during contig construction. PMID- 7987303 TI - Molecular characterization of a novel human gene, SEC13R, related to the yeast secretory pathway gene SEC13, and mapping to a conserved linkage group on human chromosome 3p24-p25 and mouse chromosome 6. AB - We previously described sequence tags from 58 novel directionally cloned human cDNAs from an enriched retinal pigment epithelial cell line library (Gieser and Swaroop, 1992). The nucleotide sequence of one of the cDNA clones, AA35 (D3S1231E), showed strong homology to the yeast SEC13 gene, required for vesicle biogenesis from endoplasmic reticulum during the transport of proteins. We have designated the human gene SEC13R (SEC13-Related). The amino acid sequence of the SEC13R gene product shows 70% similarity to yeast Sec13p, suggesting that SEC13R may be the human homolog of SEC13. The deduced polypeptide sequence contains several beta-transducin like 'WD40' repeats, and is rich in serine and threonine residues. The 1.4 kb transcript of SEC13R is detected by Northern analysis in many human tissues. However, RT-PCR analysis using two primer sets from different regions of the gene suggests differential expression of alternately spliced transcripts in various tissues. Somatic cell hybrid and in situ hybridization studies localized the SEC13R gene to human chromosome 3p24-p25. A related sequence was mapped to chromosome 18q11.2-q12. SEC13R was physically mapped to a yeast artificial chromosome (YAC) clone spanning the D3S720 marker from the region of the Von Hippel-Lindau disease locus. The mouse Sec13r gene was mapped to the conserved linkage group on chromosome 6 that corresponds to human chromosome 3p24-p25. PMID- 7987304 TI - Analysis of the tandem repeat locus D4Z4 associated with facioscapulohumeral muscular dystrophy. AB - The sequence of the tandem repeat sequence (D4Z4) associated with facioscapulohumeral muscular dystrophy (FSHD) has been determined: each copy of the 3.3 kb repeat contains two homeoboxes and two previously described repetitive sequences, LSau and a GC-rich low copy repeat designated hhspm3. By Southern blotting, FISH and isolation of cDNA and genomic clones we show that there are repeat sequences similar to D4Z4 at other locations in the human genome. Southern blot analysis of primate genomic DNA indicates that the copy number of D4Z4-like repeats has increased markedly within the last 25 million years. Two cDNA clones were isolated and found to contain stop codons and frameshifts within the homeodomains. An STS was produced to the cDNAs and analysis of a somatic cell hybrid panel suggests they map to chromosome 14. No cDNA clones mapping to the chromosome 4q35 D4Z4 repeats have been identified, although the possibility that they encode a protein cannot be ruled out. Although D4Z4 may not encode a protein, there is an association between deletions within this locus and FSHD. The D4Z4 repeats contain LSau repeats and are adjacent to 68 bp Sau3A repeats. Both of these sequences are associated with heterochromatic regions of DNA, regions known to be involved in the phenomenon of position effect variegation. We postulate that deletion of D4Z4 sequences could produce a position effect. PMID- 7987305 TI - Allelic methylation of H19 and IGF2 in the Beckwith-Wiedemann syndrome. AB - Beckwith-Wiedemann syndrome (BWS) is a congenital overgrowth syndrome with associated embryonal tumours. Most BWS cases are sporadic but familial cases occur in 15% of patients and in these there is linkage to chromosome 11p15. In addition, a small number of patients have cytogenetic abnormalities involving chromosome 11p15. Approximately 20% of sporadic BWS patients have uniparental paternal disomy (UPD) of chromosome 11p15. This finding together with the observation that penetrance in familial cases depends on parental transmission, suggests that the gene(s) for BWS are imprinted. The recent demonstration of biallelic expression of the otherwise maternally imprinted IGF2 gene in some BWS patients implicates excess IGF2 expression in the disease. Here we have analysed the allele-specific methylation patterns in the IGF2 gene and in the neighbouring and reciprocally imprinted H19 gene in a group of 42 BWS patients, 10 of which were mosaic UPD cases. We found that allelic methylation of both genes was normal in all non-UPD cases, with the paternal allele being methylated, and was increased in UPD cases in proportion with the disomic lineage. These findings suggest that sporadic BWS is not associated with a general alteration of methylation imprinting of the IGF2 and H19 genes. The methylation assay used in this study thus also offers a simple and reliable diagnostic test of UPD for 11p15.5. An unexpected finding was a distortion of the frequency of AvaII alleles at the IGF2 locus exclusively in UPD BWS cases (P < 0.001). This further implicates the IGF2 gene in aspects of the BWS phenotype. PMID- 7987306 TI - Identification of intragenic mutations in the von Hippel-Lindau disease tumour suppressor gene and correlation with disease phenotype. AB - Von Hippel-Lindau (VHL) disease is a dominantly inherited familial cancer syndrome predisposing to a variety of malignant and benign neoplasms, most frequently retinal, cerebellar and spinal haemangioblastoma, renal cell carcinoma, phaeochromocytoma and pancreatic tumours. We have previously detected large germline deletions by Southern analysis and pulsed field gel electrophoresis in 19% and 3% of VHL patients respectively. We have now investigated 94 VHL patients without large deletions for intragenic mutations using single strand conformation polymorphism and heteroduplex analysis. Forty different mutations were identified in 55 unrelated kindreds. A wide variety of mutations were detected including missense (n = 19), nonsense (n = 6), frameshift deletions or insertions (n = 12), in frame deletions (n = 2) and a splice donor site mutation (n = 1). The two most frequent mutations, were missense mutations at codon 238 (Arg-->Gln and Arg-->Trp) and were detected in five and four unrelated kindreds, respectively. VHL disease shows marked phenotypic variability and although phaeochromocytoma occurs in only about 7% of patients, marked interfamilial differences are observed. We examined the relationship between VHL gene mutations and phenotype in 65 kindreds. Large deletions or intragenic mutations predicted to cause a truncated protein were found in 36 of 53 families without phaeochromocytoma but only two of 12 families with phaeochromocytoma (chi 2 = 8.58; P < 0.01). Of 12 families with phaeochromocytoma 10 had missense mutations compared with 13 of 53 kindreds without phaeochromocytoma (chi 2 = 12.33; P < 0.001). In particular, substitution of an arginine at codon 238 (Arg- >Trp or Arg-->Gln) was associated with a high risk (62%) of phaeochromocytoma.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7987307 TI - Apo-dystrophin-1 and apo-dystrophin-2, products of the Duchenne muscular dystrophy locus: expression during mouse embryogenesis and in cultured cell lines. AB - Two promoters in the distal half of the Duchenne Muscular Dystrophy gene drive transcription of mRNAs which have novel first exons and encode the shortened forms of dystrophin, apo-dystrophin-1 (Dp71) and apo-dystrophin-2 (Dp116). Apo dystrophin-1 has a G + C rich promoter and is expressed in a wide range of cell types, whilst apo-dystrophin-2 is confined to peripheral nerve and brain. We have isolated and sequenced the unique 5' exon of rat apo-dystrophin-2 mRNA. Conceptual translation of this sequence indicates that apo-dystrophin-2 contains a unique 23 amino acid terminal peptide. Using specific probes derived from sequences at the 5' ends of apo-dystrophin-1 and apo-dystrophin-2 we have determined the expression of these two mRNAs during mouse embryonic development by RNA in situ hybridization. In contrast to full-length dystrophin, neither of these short dystrophin transcripts appear before organogenesis is well established. Apo-dystrophin-1 mRNA is detected in midline cells of the ventral neural tube and later, in the ependymal cells lining the ventricles of the brain. These results suggest that apo-dystrophin-1 mRNA is associated with glial cells in the CNS. Apo-dystrophin-1 transcripts are also abundant in the teeth primordia throughout their development. In contrast apo-dystrophin-2 mRNA is largely undetectable during development, although transcripts are seen in the newborn brain. Western blots of late human fetal tissue extracts confirm that apo dystrophin-2 is most abundant in brain and analysis of RNA and protein in cultured cell lines reveal expression of apo-dystrophin-1 and apo-dystrophin-2 in glioma cells. PMID- 7987308 TI - The glycerol kinase gene family: structure of the Xp gene, and related intronless retroposons. AB - The human glycerol kinase gene family consists of at least six genomic loci, four of which encode expressed sequences. The X-linked gene responsible for GKD maps to Xp21.3. Analysis of cosmid and YAC clones shows that this locus is in excess of 50 kbp, and is comprised of 19 exons. In contrast, the remaining members of the gene family, on chromosomes 1, 4 and Xq, appear to be organized as intronless genes. Northern analysis shows expression of GK transcripts of three sizes in a wide range of adult tissues. Only the smallest hybridizing species is present in testis where it occurs at an elevated level. Two different testis transcripts have been identified and both of these originate from chromosome 4. PMID- 7987309 TI - Coproporphyrinogen oxidase: gene organization and description of a mutation leading to exon 6 skipping. AB - Genomic clones containing a human coproporphyrinogen oxidase gene, were isolated. DNA sequencing indicates that the human CPX gene spans about 14 kb and consists of seven exons and six introns. Sequences were determined for all the exons, exon intron junctions and for 800 bp of promoter region. Introns vary in size from 269 bp to 5 kb and they all have consensus sequences at their boundaries. Primer extension and ribonuclease protection experiments revealed multiple transcriptional initiation sites in a region with sequence motifs characteristic of a promoter. The promoter region is GC-rich and contains multiple potential Sp 1 elements, CACCC boxes and potential GATA-1 binding sites. The availability of the CPX genomic sequence allowed us to determine the mutation in a patient with a hereditary coproporphyria. AG to A mutation was found at the last position of exon 6. This mutation results in exon skipping. PMID- 7987310 TI - Identification of a Bardet-Biedl syndrome locus on chromosome 3 and evaluation of an efficient approach to homozygosity mapping. AB - Bardet-Biedl syndrome is an autosomal recessive disorder characterized by mental retardation, obesity, retinitis pigmentosa, polydactyly and hypogonadism. Individuals with this disorder also have an increased incidence of hypertension, diabetes mellitus, and renal and cardiac anomalies. We previously identified a locus on chromosome 16 causing this disorder, and provided evidence that Bardet Biedl syndrome is heterogeneous. In this study, we identify another Bardet-Biedl syndrome locus on chromosome 3 and confirm the non-allelic heterogeneity of this disorder in Bedouin populations. In addition, we demonstrate the feasibility of using pooled DNA samples from members of large kindreds as an efficient approach to homozygosity mapping. PMID- 7987311 TI - Double crossover in the human Xp/Yp pseudoautosomal region and its bearing on interference. AB - Most models on crossover and crossover interference have assumed that the intensity of interference depends inversely on the physical distance separating the respective intervals. The possibility, however, also exists that interference depends on genetic rather than on physical distance. As the human pseudoautosomal region (PAR) on Xp/Yp is physically small, yet genetically a hot spot of recombination in male meiosis, studies on the existence of multiple crossover events may be particularly useful in addressing the question of interference. Our results demonstrate for the first time a double crossover during male meiosis in the human PAR on Xp/Yp. The occurrence of a single obligatory recombination event in this region can, therefore, no longer be taken as a dogma. However, double crossover events seem to remain exceptional and, thus, the model originally suggested by Burgoyne remains globally correct. As both recombination events can be localized within a narrow range of physical distance, theories describing interference due to steric hindrance may have to be reconsidered. This finding may, therefore, have general implications for our understanding of the mechanism of positive and negative crossover interference in mammalian genomes and may be interesting especially for linkage mapping where double recombinations in small intervals tend to be considered as genotyping errors. PMID- 7987312 TI - Characterization of an 800 kb region at 3p22-p21.3 that was homozygously deleted in a lung cancer cell line. AB - We have characterized a homozygous deletion at 3p22-p21.3 found in a lung cancer cell line ACC-LC-5. Three yeast artificial chromosomes (YACs) were isolated from a YAC library by hybridization with two cosmid probes (cCI3-1994 and cCI3-1999) representing loci that were homozygously deleted in five lung cancer cell lines. Cloning both ends of the region deleted in the cell line ACC-LC-5 revealed the deletion was an interstitial deletion within the chromosomal arm. A cosmid contig map covering the entire region corresponding to the homozygous deletion was constructed by means of Southern hybridizations. From these results and analyses by pulsed-field gel electrophoresis, this interstitial deletion on chromosome 3p22-21.3 in this cell line was estimated to be nearly 800 kb long and is smallest among five cell lines containing the homozygous deletion. The cosmid clones representing this region will contribute important new resources for isolating the putative tumor suppressor gene(s) on chromosome 3p22-21.3. PMID- 7987313 TI - Physical mapping of the split hand/split foot locus on chromosome 7 and implication in syndromic ectrodactyly. AB - Split hand/split foot (ectrodactyly; SHSF) is a human developmental malformation characterized by missing digits and claw-like extremities. An autosomal dominant form of this disorder has been mapped to 7q21.3-q22.1; the locus has been designated SHFD1. We have constructed a physical map consisting of overlapping yeast artificial chromosome clones for the entire region. Somatic cell hybrid and fluorescent in situ hybridization analyses were used to define SHSF-associated chromosomal rearrangements in twelve patients. An SHFD1 critical interval of 1.5 Mb was established by analysis of five patients with deletions. Translocation or inversion breakpoints found in six patients were mapped within 700 kb of each other in the critical region. Of note is that eight of the patients analyzed (67%) are in fact classified as having syndromic ectrodactyly. Thus, these mapping data establish a relationship between simple split hand/split foot and this more complex group of human birth defects. Finally, we have mapped DLX5, a member of the Distal-less homeobox gene family, to the SHFD1 critical interval. PMID- 7987314 TI - Familial split hand/split foot long bone deficiency does not segregate with markers linked to the SHFD1 locus in 7q21.3-q22.1. AB - Ectrodactyly (split hand/split foot, SHSF) is characterized by the absence of middle rays of the hand or the foot. Cytogenetic analyses of some of the cases have indicated an association between chromosomal rearrangements involving 7q21.3 q22 and ectrodactyly. Based on these observations, an autosomal dominant form of ectrodactyly is assumed to reside in this region and the locus has been designated SHFD1 (split hand/split foot disorder). Here we report a large family where split hand/split foot long bone deficiency (SHFLD) segregates in an autosomal dominant mode. Linkage analysis, using microsatellite markers located in 7q21-q22, excludes this region from containing the gene responsible for SHFLD in this family. These results would appear to indicate genetic heterogeneity exists in autosomal dominant SHSF. PMID- 7987315 TI - Isolation of a diverged homeobox gene, MOX1, from the BRCA1 region on 17q21 by solution hybrid capture. AB - Using the technique of solution hybridization coupled with magnetic bead capture, we have isolated a novel homeobox-containing gene from the BRCA1 region of 17q21. This gene is the human homologue of the mouse Mox1 gene previously localized to a syntenic region of mouse chromosome 11. Multiple overlapping cDNAs of human MOX1 were identified using both a cosmid and a P1 genomic clone containing the microsatellite markers D17S750 and D17S858 which map within the BRCA1 region defined by D17S776 and D17S78. MOX1 expression was observed in a variety of normal tissues examined, including breast and ovary. Given that the gene contains a homeobox domain and has the potential to regulate growth and differentiation, MOX1 represents an attractive candidate for the BRCA1 gene. This possibility was investigated in a series of BRCA1 kindreds and primary sporadic breast tumors. No evidence for mutation was found in the coding sequence, making it unlikely that MOX1 is the BRCA1 gene. However, the widespread expression of MOX1 in non embryonal tissues suggests a role in normal cell biology which warrants further study. PMID- 7987316 TI - The origin of 47,XXY and 47,XXX aneuploidy: heterogeneous mechanisms and role of aberrant recombination. AB - We investigated the parent and cell division of origin of the additional sex chromosome in 142 males with a 47,XXY constitution and 50 females with a 47,XXX constitution. In 66 of the 47,XXY males the additional chromosome was paternal in origin and in 76 it was maternal in origin, while among the 47,XXX females only 5 had an additional paternal X chromosome, the remaining 45 having an additional maternal chromosome. Among the 107 maternally derived aneuploids for whom it was possible to determine the cell division of origin, 73 were the result of a mat MI error, 24 the result of a mat MII error and 10 the result of a post zygotic mitotic (PZM) error involving the maternal X chromosome. Among those in which the non-disjunction was attributable to an error at the first meiotic division (MI) we observed three different mechanisms of origin. Approximately 30% were associated with complete absence of recombination (nullichiasmate); approximately 24% were associated with a normal number of recombinant events but an abnormal distribution of exchanges (perturbed recombination), while approximately 45% were associated with a normal number and distribution of recombinant events (normochiasmate). Nondisjunction due to an error at the second meiotic division (MII) was associated with a slight reduction in the total number of recombinant events and an abnormal distribution of exchanges. Thus of the four different meiotic mechanisms of origin, three were associated with an abnormal number and/or distribution of exchange events. There was no evidence of an increased paternal age in the aneuploids of paternal origin.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7987317 TI - Early embryonic failure associated with uniparental disomy for human chromosome 21. AB - As many as 16% of all recognized pregnancies may be anembryonic, with failure of the embryo at a very early stage of development leaving only the extraembryonic components of the conceptus to proliferate. Studies in the mouse have shown that the maternal and paternal contributions to the genome of the zygote are not functionally equivalent, due to parental genomic imprinting. Uniparental disomy can reveal imprinting effects, as in this phenomenon both members of a chromosome pair are inherited from the same parent. We have carried out a systematic search for uniparental disomy in tissues from 23 cases of early embryonic failure, using variable number tandem repeat (VNTR) analysis and PCR amplification of polymorphic short sequence repeats. Two cases of maternal uniparental heterodisomy for chromosome 21 were identified. One case occurred in conjunction with trisomy for chromosomes 7 and 9, but in the other case maternal uniparental heterodisomy for chromosome 21 was the only chromosomal abnormality found. We therefore postulate that there may be developmentally important genes on human chromosome 21 which are imprinted such that both parental copies are essential for normal embryogenesis. PMID- 7987319 TI - Addition of functional human telomeres to YACs. AB - Linear mammalian artificial chromosomes (MACs) will require functional telomeres, a centromere and the ability to replicate autonomously. We are investigating the possibility of developing MACs from yeast artificial chromosomes (YACs). Retrofitting vectors have been constructed to replace YAC telomeres with cloned human telomeric DNA. A modified YAC was introduced into mammalian cells by spheroplast fusion and the frequency with which the retrofitted human telomeric DNA seeded the formation of a new telomere was determined by Bal31 digestion and cytogenetic analysis. The telomere adjacent to the selectable marker gene was functional in 5/46 clones (11%) while the telomere 200 kb away at the other end of the YAC was functional in 1/46 clones (2%). These results indicate that despite the in vivo modification of the end of the telomere by the addition of yeast sequences, human telomeres will function at a high enough frequency to allow the construction of MACs by this route. PMID- 7987318 TI - Sequence, expression and characterization of HPRTMoose Jaw: a point mutation resulting in cooperativity and decreased substrate affinities. AB - We have sequenced and studied the expressed protein of an HPRT mutation characterized by 5-12% residual erythrocyte activity, for which affected males exhibit hyperuricemia, arthritis and renal disease but are without severe neurological involvement. The HPRTMoose Jaw mutation is due to a single C to G transversion at nucleotide 582 relative to initiation of translation corresponding to substitution of aspartate 194 by glutamate. The mutant and wild type proteins were expressed and purified using the bacterial expression vector, pMAL-c2. The Km for hypoxanthine was increased 12-fold from 0.94 +/- 0.26 to 11.5 +/- 1.3 microM for control and mutant respectively. The apparent Km for PP-ribose P was increased 44-fold from 6.8 +/- 0.6 to 295 +/- 7 microM for control and mutant respectively. Although the kcat of the mutant protein was equivalent to wild type, the catalytic efficiency, kcat/Km, of the purified mutant protein was only 6 and 3% of wild type with hypoxanthine and PP-ribose-P respectively. The mutant protein also exhibited positive cooperativity with PP-ribose-P, having a Hill coefficient of 2.3. The decreased substrate affinities and PP-ribose-P associated cooperativity of HPRTMoose Jaw provide additional evidence for the influence of carboxy-terminal residues of HPRT in specific catalytic functions. PMID- 7987320 TI - Junctional epidermolysis bullosa inversa (locus EBR2A) assigned to 1q31 by linkage and association to LAMC1. AB - Junctional epidermolysis bullosa inversa is an autosomal recessive blistering skin disease with an ultrastructural hemidesmosome defect similar to that of the Herlitz disease, yet with a non-lethal and different course of the disease. Its delineation is based on five geographically associated Norwegian families where all parents are likely to carry a mutant EBR2A allele identical in descent. Three informative families show a lod score of +1.65 at zero recombination to a trinucleotide repeat marker in intron 20 of the laminin gamma 1 (LAMC1, previously LAMB2) locus on 1q31. The four patients of these families are all homozygous for the 146 bp LAMC1 allele present only on 5% of random Norwegian chromosomes. The daughter of a deceased patient in a fourth family carries the same 146 bp allele. This extreme association confirms that the disease locus, EBR2A, is at or closely linked to LAMC1. Localized and generalized Mitis types as well as the majority of tested families with the Herlitz type of junctional epidermolysis bullosa appeared not to be similarly linked or associated to LAMC1. The MspI and AluI RFLPs of LAMC1 showed absolute allelic association. Each of the two RFLP haplotypes showed association to either 'long' or 'short' intron 20 STR alleles. PMID- 7987321 TI - Characterization of a new member of the human beta-adaptin gene family from chromosome 22q12, a candidate meningioma gene. AB - A 140 kb homozygous deletion from 22q12 in one meningioma directed us towards the cloning and characterization of a new member of the human beta-adaptin gene family (named BAM22). Adaptins are essential for the formation of clathrin coated vesicles in the course of intracellular transport of receptor-ligand complexes. The BAM22 gene is totally inactivated in the tumor with homozygous deletion. Northern blot analysis of 70 sporadic meningiomas showed specific loss of expression in 8 tumors, suggesting inactivation of BAM22. Based on this, we propose BAM22 as a second chromosome 22 locus important in meningioma development, after the neurofibromatosis type 2 gene. PMID- 7987322 TI - Identification of a locus, distinct from RDS-peripherin, for autosomal recessive retinitis pigmentosa on chromosome 6p. AB - We performed a genomic search for linkage to autosomal recessive retinitis pigmentosa in a large pedigree obtained from the Dominican Republic using microsatellite markers. Regions of the genome known to contain genes for retinitis pigmentosa were preferentially tested. One of these regions, on chromosome 6p, which contains the gene for peripherin, gave positive lod scores. Use of a mononucleotide repeat polymorphism in the peripherin gene excluded this locus. Two- and multi-point analyses suggest that the most likely location for the disease gene is near D6S291, which is located approximately 20 centimorgans telomeric from peripherin. PMID- 7987323 TI - Localization of the genetic locus for Saethre-Chotzen syndrome to a 6 cM region of chromosome 7 using four cases with apparently balanced translocations at 7p21.2. AB - Saethre-Chotzen syndrome is a common autosomal dominant form of craniosynostosis, which results in the premature fusion of cranial sutures. Craniosynostosis is commonly associated with abnormalities of 7p; Vortkamp et al. (Nature 352, 539 540) demonstrated that the GLI3 gene in 7p13 was disrupted in, patients with Greig syndrome and, more recently, the linkage of genetic markers from 7p with the Saethre-Chotzen syndrome locus has been reported (2,3). Here we report the analysis by fluorescence in situ hybridization of four patients with Saethre Chotzen syndrome associated with apparently balanced translocations involving band 7p21.2 and different reciprocal chromosomes. We show that in all four patients the breakpoints in 7p are situated within a 6 cM region flanked by the genetic markers D7S488 and D7S493. These results provide further evidence that the genetic locus for Saethre-Chotzen syndrome is located in distal 7p. PMID- 7987324 TI - Angelman syndrome associated with a maternal 15q11-13 deletion of less than 200 kb. AB - Angelman syndrome (AS) is a neurogenetic disorder arising from a lack of genetic contribution from the maternal chromosome 15q11-13. To date, the AS critical region has been defined by an inherited deletion of approximately 1.5Mb, spanning the 3-21 (D15S10), LS6-1 (D15S113) and GABRB3 loci. We have identified an individual with the typical features of AS who has a deletion of the maternal chromosome which encompasses LS6-1, but does not extend to either flanking marker. This deletion, initially detected by (CA)n repeat analysis, was further characterised by fluorescence in situ hybridisation (FISH) using cosmids derived from a 260 kb LS6-1 yeast artificial chromosome (YAC). Neither end cosmid from this YAC clone falls within the deletion, suggesting that the minimal AS region is less than 200 kb. We also studied three loci within 15q11-13 which detect parent-of-origin specific DNA methylation imprints, and found that both normal maternal and paternal patterns were present in this patient. PMID- 7987326 TI - Identification of a new mutation at codon 171 of rhodopsin gene causing autosomal dominant retinitis pigmentosa. PMID- 7987325 TI - A calcium channel mutation causing hypokalemic periodic paralysis. AB - The only calcium channel mutation reported to date is a deletion in the gene for the DHP-receptor alpha 1-subunit resulting in neonatal death in muscular dysgenesis mice (1). In humans, this gene maps to chromosome 1q31-32. An autosomal dominant muscle disease, hypokalemic periodic paralysis (HypoPP), has been mapped to the same region (2). Sequencing of cDNA of two patients revealed a G-to-A base exchange of nucleotide 1583 predicting a substitution of histidine for arginine528. This affects the outermost positive charge in the transmembrane segment IIS4 that is considered to participate in voltage sensing. By restriction fragment analysis, the mutation was detected in the affected members of 9 out of 25 HypoPP families. The results indicate that the DHP-receptor alpha 1-subunit mutation causes HypoPP. An altered excitation-contraction coupling may explain the occurrence of muscle weakness. PMID- 7987327 TI - A novel mutation in the von Hippel-Lindau gene. PMID- 7987328 TI - Are CpG sites mutation hot spots in the dystrophin gene? PMID- 7987329 TI - A novel splice site mutation in intron 1 of the GALNS gene in a Japanese patient with mucopolysaccharidosis IVA. PMID- 7987330 TI - Novel mutations in the V2 vasopressin receptor gene of patients with X-linked nephrogenic diabetes insipidus. PMID- 7987331 TI - Five novel missense mutations of the rhodopsin gene in autosomal dominant retinitis pigmentosa. PMID- 7987332 TI - Complete mtDNA sequence of a patient in a maternal pedigree with sensorineural deafness. PMID- 7987333 TI - A novel nonsense mutation in the HMG box of the SRY gene in a patient with XY sex reversal. PMID- 7987334 TI - A 7 bp deletion of the RET proto-oncogene in familial Hirschsprung's disease. PMID- 7987335 TI - Dinucleotide repeat polymorphisms at the D5S1356, D5S1357 and D7S1480 loci. PMID- 7987336 TI - An RsaI polymorphism for the fibrillin gene (FBN1). PMID- 7987337 TI - Dinucleotide repeat polymorphism at the DXS1684 locus. PMID- 7987338 TI - An A to G polymorphism in the SHBG gene. PMID- 7987339 TI - Two dinucleotide repeat polymorphisms at 17p13. PMID- 7987340 TI - DdeI polymorphism in the AGTR1 gene. PMID- 7987341 TI - SSCP at the HTR1DA locus. PMID- 7987342 TI - A (GA)n repeat polymorphism in the human protamine 2 (PRM 2) gene. PMID- 7987343 TI - Dinucleotide repeat polymorphism at the CHRND locus. PMID- 7987344 TI - Dinucleotide repeat polymorphism within the choroideremia gene at Xq21.2. PMID- 7987345 TI - Emergence of bulimia nervosa as a separate diagnostic entity: review of the literature from 1960 to 1979. AB - With Russell's description of bulimia nervosa in 1979, followed by the DSM-III diagnosis of bulimia, a "new" eating syndrome found its official acceptance in the scientific world. In the two preceding decades clinicians and researchers gradually payed more attention to special forms of overeating. In the 1970s the nosographic conceptualizations of binge eating, bulimia, compulsive eating, or hyperorexia clearly shifted from a symptom level--closely connected to anorexia nervosa and/or obesity--to a syndrome level. Around the same time and independently from one another, clinicians from different countries proposed various descriptive labels for this new diagnostic entity, which, finally, became accepted as bulimia nervosa. PMID- 7987347 TI - Hyperorexia nervosa. 1976. PMID- 7987346 TI - About a particular type of oral perversion in the female: hyperphagia followed by vomiting. 1972. PMID- 7987348 TI - Bulimia nervosa with and without alcoholism: a comparative study in Japan. AB - To characterize females with bulimia nervosa and alcoholism, this study compared the social and family backgrounds, as well as the clinical symptoms of alcoholics with bulimia and patients with bulimia only. The subjects were 22 Japanese female patients with both bulimia nervosa and alcoholism; the comparison group comprised 22 age-matched female patients with bulimia nervosa but without alcoholism. Patients with both bulimia and alcoholism had more borderline personality disorders and pathological symptoms such as stealing, suicide attempts, and liver injuries than the nonalcoholic comparison group. The subjects' average body weight was significantly less than that of the comparison group. Whereas the clinical characteristics of females with bulimia and alcoholism differ in many respects from those with bulimia only, it is suggested that alcoholic bulimia patients form a distinct clinical subgroup among patients with bulimia nervosa. PMID- 7987349 TI - Binge eating disorder and the proposed DSM-IV criteria: psychometric analysis of the Questionnaire of Eating and Weight Patterns. AB - Proposed binge eating disorder (BED) diagnostic criteria were investigated to provide necessary psychometric characteristics and explore their utility in assessment. One hundred four subjects (52 self-referred bingers, 52 comparison subjects) completed an initial administration of the Questionnaire of Eating and Weight Patterns (QEWP). The results supported the ability of the two core BED criteria (i.e., episodic overeating, loss of control) to discriminate between clinical and nonclinical binge eaters. Thirty-nine of the self-referred and 40 of the comparison subjects completed a second QEWP administration 3 weeks later. Results indicated that the BED diagnosis was moderately stable over the 3-week interval (kappa = .58, combined sample). Using self-monitoring data completed by the self-referred subjects, predictive efficiency analyses indicated that the QEWP was able to identify both high and low probability binge eaters. Implications of the findings for the definition, assessment, and utility of the BED diagnosis are discussed. PMID- 7987350 TI - Heart rate power spectrum analysis of autonomic dysfunction in adolescents with anorexia nervosa. AB - We studied autonomic modulation of heart rate in 8 females with anorexia nervosa (AN) using power spectral analysis (PSA) of heart rate variability in the supine and standing positions at baseline and after 2 weeks of intensive nutritional rehabilitation, and compared findings with healthy female control subjects. The results indicate that there is a decrease in sympathetic modulation of heart rate, evident by a deficit of low frequency (0.01-0.15 Hz) heart rate power in the supine position in AN compared with control subjects. In addition, parasympathetic modulation of heart rate failed to decrease with standing. A trend toward improvement in autonomic control of heart rate in adolescents with AN occurs in the supine position relatively early in weight rehabilitation. PSA is a sensitive, quantitative, and noninvasive means of determining autonomic control of heart rate and could be a useful tool in monitoring the health of patients with AN. PMID- 7987351 TI - From the Cleavers to the Clintons: role choices and body orientation as reflected in magazine article content. AB - The media have been heavily implicated as sources of overconcern with body focus, attractiveness, and thinness, primarily for women. Attendant negative consequences are widely assumed. Yet there appears to be a recent media trend to concern with physical health and fitness, rather than just appearance. This trend has not been empirically assessed. Further, previous research has not adequately explored the possibility that there may be an assortment of physical ideals represented in the media, which may vary according to the different audiences being targeted. The current study assessed magazine article content, examining gender differences, time trends, and magazine audience type. Four types of article content were examined: health, fitness, beauty, and weight loss, in an attempt to capture the major aspects of body focus. The numbers of articles containing such content were tallied, over a 12-year period, in a sample of magazines oriented to three distinct audiences: traditional, high fashion, and modern. Huge gender differences were obtained, with female-targeted magazines not surprisingly outstripping male-targeted ones for all content categories assessed. There were also clear differences in content between magazine types. Time-trend analyses indicated a decrease in emphasis on weight loss in women's magazines over the period studied, and a statistical trend for an increase in weight loss focus in men's magazines. We conclude that apparent trends toward healthier habits are not just thinness goals revisited. PMID- 7987352 TI - Examination of the use of smoking for weight control in restrained and unrestrained eaters. AB - Recent research has examined the perceived benefits of smoking and suggests that continued smoking may be related to contemporary concerns for weight and shape. The present study examined the role of restrained eating in predicting smoking for reasons of weight control, reports of weight gain following cessation, and reasons for relapse and intentions to quit. Eighty-four restrained eaters and 83 unrestrained eaters completed a questionnaire examining their smoking behavior. The results suggest that the restrained eaters gave significantly greater endorsement than the unrestrained eaters to statements relating to smoking initiation and smoking maintenance for weight control, the role of weight gain in previous experiences of smoking relapse, intentions to quit following weight loss, and intentions to quit in 5 years. No differences were found between the restrained and unrestrained eaters in terms of experiences of post cessation weight gain, the number of attempts to quit, and intentions to quit in 6 months. The results are discussed in terms of developing a model of the relationship between smoking and weight concerns. PMID- 7987353 TI - Construct validity of the Three-Factor Eating Questionnaire: flexible and rigid control subscales. AB - This study investigated the construct validity of two dietary restraint subscales, flexible control (FC) and rigid control (RC), identified by Westenhoefer (1991; Appetite, 16, 45-55) as a subset of the restraint scale items from the Three-Factor Eating Questionnaire (TFEQ, Stunkard & Messick. [1985]. Journal of Psychosomatic Research, 29, 71-83). The subjects were 31 women on long term personality disorder units. Based on the Structured Clinical Interview for DSM-III-R (SCID), 68% has past anorexia and/or bulimia diagnoses and 94% were borderline. The subjects completed the TFEQ and supplied weight and height data for body mass index (BMI) calculations. The results supported the validity of the two restraint constructs by showing that FC was inversely related to BMI and predicted an anorexia diagnosis. In contrast, RC directly predicted BMI when tested concurrently with FC. RC was also more associated with a history of bulimia and problems with weight fluctuations than FC was. Thus, the FC-RC distinction was valid and useful in this population of women. PMID- 7987354 TI - Waist-to-hip ratio and body dissatisfaction among college women and men: moderating role of depressed symptoms and gender. AB - We examined the interrelationships of waist-to-hip ratio (WHR), body dissatisfaction, gender, and depressed and eating disordered symptoms cross sectionally among 131 male and female undergraduates. Based on past findings on physical and mental health, attractiveness, and depressive realism, we predicted that the WHR x Depression x Gender interaction would be significantly related to body dissatisfaction, such that the correspondence between WHR and body dissatisfaction would be more pronounced among depressed than among nondepressed women and men. This hypothesis received support. Implications of our results for work on body dissatisfaction were discussed. PMID- 7987355 TI - Neuromyopathic complications in a patient with anorexia nervosa and vitamin C deficiency. AB - A 19-year-old female patient with anorexia nervosa developed profound weight loss over 1 year associated with vegetarianism and excessive exercise. There was severe wasting and proximal muscle weakness in the legs and bilateral weakness of eye closure. A purpuric rash developed due to vitamin C deficiency. This case demonstrates a new neurological sign in anorexia nervosa indicating a weakness of the orbicularis oculi muscles as part of a more general myopathy. The myopathic and scorbutic features may have a common pathogenesis. PMID- 7987356 TI - "Or at least, to do no harm". PMID- 7987357 TI - Free radicals, exercise, and antioxidant supplementation. AB - Free radicals have been implicated in the development of diverse diseases such as cancer, diabetes, and cataracts, and recent epidemiological data suggest an inverse relationship between antioxidant intake and cardiovascular disease risk. Data also suggest that antioxidants may delay aging. Research has indicated that free radical production and subsequent lipid peroxidation are normal sequelae to the rise in oxygen consumption with exercise. Consequently, antioxidant supplementation may detoxify the peroxides produced during exercise and diminish muscle damage and soreness. Vitamin E, beta carotene, and vitamin C have shown promise as protective antioxidants. Other ingestible products with antioxidant properties include selenium and coenzyme Q10. The role (if any) that free radicals play in the development of exercise-induced tissue damage, or the protective role that antioxidants may play, remains to be elucidated. Current methods used to assess exercise-induced lipid peroxidation are not extremely specific or sensitive; research that utilizes more sophisticated methodologies should help to answer many questions regarding dietary antioxidants. PMID- 7987358 TI - Carbohydrate, fluid, and electrolyte requirements of the soccer player: a review. AB - Soccer requires field players to exercise repetitively at high intensities for the duration of game, which can result in marked muscle glycogen depletion and hypoglycemia. A soccer match places heavy demands on endogenous muscle and liver glycogen stores and fluid reserves, which must be rapidly replenished when players complete several matches within a brief period of time. Low concentrations of muscle glycogen have been reported in soccer players before a game, and daily carbohydrate (CHO) intakes are often insufficient to replenish muscle glycogen stores. CHO supplementation during soccer matches has been found to result in muscle glycogen sparing (39%), greater second-half running distances, and more goals being scored with less conceded, when compared to consumption of water. Thus, CHO supplementation has been recommended prior to, during, and after matches. In contrast, there is currently insufficient evidence to recommend without reservation the addition of electrolytes to a beverage for ingestion by players during a game resulting in sweat losses of < 4% of body weight. PMID- 7987359 TI - Self-esteem: its application to eating disorders and athletes. AB - Self-esteem, a hierarchical and multifactorial perception, can be described as the extent to which a person feels positive about himself or herself. Social factors such as life satisfaction, sex, age, and strongly held values can affect self-esteem. Low self-esteem is a well-recognized trait of those with eating disorders and may be associated with a heightened self-awareness. Body dissatisfaction, common among women in Western society, may enhance this awareness. Athletes, especially those with eating disorders, are perfectionists and have acute body awareness and a sense of loss of control. Control is a crucial issue with these athletes. Before any nutrition counseling starts, readiness to listen should be assessed in conjunction with a mental health professional. Various tools are available to assess the eating disordered athlete's self-esteem, body image, and eating behavior. Nutrition counseling can help the athlete overcome an eating disorder by clarifying misconceptions and focusing on the role of nutrition in promoting health and athletic performance. PMID- 7987360 TI - alpha-Tocopherol supplementation in racing cyclists during extreme endurance training. AB - This study was undertaken to evaluate the effects of 5 months of alpha-tocopherol supplementation on physical performance during aerobic exercise training in 30 top-class cyclists. Antioxidative effects of supplementation were also studied. Plasma alpha-tocopherol concentration increased significantly in the vitamin E supplemented group, whereas the placebo group showed a trend toward decrease. Physical performance did not improve in the alpha-tocopherol-supplemented group compared to the placebo group. Heart rates were also not significantly different. Lactate concentrations at the aerobic threshold and the anaerobic threshold were identical. Thus, there was no performance improvement in the alpha-tocopherol supplemented group. However there was a significant reduction in CK in serum of the E-supplemented group. A trend toward decrease in GOT, GPT, and LDH was observed with alpha-tocopherol supplementation. Moreover, significantly reduced malondialdehyde serum levels were measured in the E-supplemented group. The findings indicate a protective effect of alpha-tocopherol supplementation against oxidative stress induced by strenuous exercise. PMID- 7987361 TI - Urinary indices of hydration status. AB - Athletes and researchers could benefit from a simple and universally accepted technique to determine whether humans are well-hydrated, euhydrated, or hypohydrated. Two laboratory studies (A, B) and one field study (C) were conducted to determine if urine color (Ucol) indicates hydration status accurately and to clarify the interchangeability of Ucol, urine osmolality (Uosm), and urine specific gravity (Usg) in research. Ucol, Uosm, and Usg were not significantly correlated with plasma osmolality, plasma sodium, or hematocrit. This suggested that these hematologic measurements are not as sensitive to mild hypohydration (between days) as the selected urinary indices are. When the data from A, B, and C were combined, Ucol was strongly correlated with Usg and Uosm. It was concluded that (a) Ucol may be used in athletic/industrial settings or field studies, where close estimates of Usg or Uosm are acceptable, but should not be utilized in laboratories where greater precision and accuracy are required, and (b) Uosm and Usg may be used interchangeably to determine hydration status. PMID- 7987362 TI - Effect of L-carnitine supplementation on muscle and blood carnitine content and lactate accumulation during high-intensity sprint cycling. AB - This study examined the effects of 14 days of L-carnitine supplementation on muscle and blood carnitine fractions, and muscle and blood lactate concentrations, during high-intensity sprint cycling exercise. Eight subjects performed three experimental trials: control I (CON I, Day 0), control II (CON II, Day 14), and L-carnitine (L-CN, Day 28). Each trial consisted of a 4-min ride at 90% VO2max, followed by a rest period of 20 min, and then five repeated 1-min rides at 115% VO2max (2 min rest between each). Following CON II, all subjects began dietary supplementation of L-carnitine for a period of 14 days (4 g/day). Plasma total acid soluble and free carnitine concentrations were significantly higher (p < .05) at all time points following supplementation. L-carnitine supplementation had no significant effect on muscle carnitine content and thus could not alter lactate accumulation during exercise. PMID- 7987363 TI - The relationship between cardiorespiratory fitness, physical activity, and dietary quality. AB - This study evaluated the relationship between cardiorespiratory fitness, physical activity, and dietary quality in a group of 20- to 40-year-old women (n = 34) who varied widely in levels of physical activity. Nutrient intakes were determined using 10 repeated 24-hr diet records, randomly assigned, over a 10-week period. Physical activity was determined on the same randomly assigned days using the Caltrac Personal Activity Computer. Cardiorespiratory fitness was assessed by two maximal graded treadmill tests with continuous metabolic monitoring at both the beginning and end of the 10-week period. Neither physical activity nor cardiorespiratory fitness was significantly correlated with nutrient density (nutrient/1,000 kcal). Intake of energy (kcal/kg body weight) was higher for the more physically active and fit women, leading to a significant increase in most nutrients consumed per kilogram of body weight. PMID- 7987364 TI - Substrate responses to submaximal exercise in the midfollicular and midluteal phases of the menstrual cycle. AB - This study examined substrate metabolism responses of eumenorrheic women to different intensities of submaximal exercise at the midfollicular (MF) and the midluteal (ML) phases of the menstrual cycle. Nine women performed a 30-min treadmill run in which the exercise intensity was made more difficult every 10 min (35%, 60%, and 75%). Carbohydrate (CHO) utilization and oxidation rates for the 35% and 60% intensities during the ML session were significantly lower than during the comparable intensities in the MF. Conversely, lipid utilization and oxidation were significantly greater during the 35% and 60% ML session than in the MF session. At 75%, however, the ML and MF CHO-lipid utilization and oxidation rates were not significantly different from one another. Thus, the phase of the menstrual cycle in eumenorrheic women does influence metabolic substrate usage during low- to moderate-intensity submaximal exercise, probably due to changes in the endogenous levels of the female sex hormones. PMID- 7987365 TI - Electrical stimulation of the rat periventricular nucleus influences the activity of hypothalamic arcuate neurones. AB - In rats, the release of growth hormone (GH) is inhibited during electrical stimulation of the periventricular nucleus but after the end of stimulation, there is a rebound 'hypersecretion' of GH. We examined the responses of arcuate neurones in pentobarbitone-anaesthetized male rats, following electrical stimulation of the periventricular nucleus to test the hypothesis that the effects of periventricular nucleus stimulation on GH secretion are mediated via effects upon GH-releasing hormone (GRF) neurones in the arcuate nucleus. The electrical activity of 2 groups of arcuate neurones were analysed before, during and after periventricular nucleus stimulation (10 Hz, 5 min, 0.5 mA biphasic, 0.5/1.0 ms): a) putative neurosecretory cells which were antidromically identified (AD) as projecting to the median eminence (n = 53) and b) non neurosecretory cells, identified by their spontaneous 'bursting' pattern of activity (n = 29). During stimulation predominantly inhibitory responses were observed in both AD and bursting cell groups. Of the 39 AD cells which were spontaneously active, 25 were inhibited during the periventricular nucleus stimulation, and 10 of these showed a rebound hyperactivation following the end of stimulation. Fifteen bursting cells were inhibited during stimulation and 4 of these displayed a rebound hyperactivation following the end of stimulation. Additional evidence was sought for the identity of these cells by testing their response to electrical stimulation of the basolateral amygdala (which has previously been shown to increase plasma GH concentration without influencing the release of other pituitary hormones).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7987366 TI - Systemic osmotic stimulation increases vasopressin and oxytocin release within the supraoptic nucleus. AB - Vasopressin (VP) and oxytocin (OT) are released within the hypothalamic nuclear region in response to direct microdialysis with hypertonic solutions. Experiments were performed to determine whether systemic osmotic stimulation causes changes in intranuclear peptide release within the supraoptic nucleus (SON). A hypertonic sodium chloride solution was injected intraperitoneally (i.p.) or intravenously (i.v.) and microdialysis techniques were used to simultaneously monitor central and peripheral peptide release in urethane anesthetized rats. Systemic osmotic stimuli elicited increases in intranuclear peptide release which were delayed and long-lasting, occurring over a 2.5 h period. In contrast, plasma peptide levels peaked at 30-min after the stimulus. The results demonstrate that increased plasma sodium elicits an increase in VP and OT release into the extracellular space of the hypothalamic SON. The different patterns of peptide release in plasma and brain point toward the possibility of independently regulated release into the different compartments. PMID- 7987367 TI - Hypothalamic-pituitary-adrenal activation following endotoxin administration in the developing rat: a CRH-mediated effect. AB - The present studies assessed hypothalamic-pituitary-adrenal (HPA) responses following immune activation with endotoxin (i.p.) in three-day old Long Evans rats. Marked plasma corticosterone (B), adrenocorticotrophic hormone (ACTH) responses and biphasic fluctuations in plasma glucose were maximal at a dose of 0.05 mg/kg. HPA responses peaked between 3-5 h following immune challenge and plasma ACTH and B responses were greater in female than in male rat pups. Plasma levels of corticosterone binding globulin (CBG) were reduced in males and substantially increased in females during the peak HPA response. Changes in plasma glucose were biphasic with slight increases when ACTH and B levels were maximal, but hypoglycemia was evident once plasma B levels returned to resting values. Endotoxin challenge reduced median eminence corticotropin-releasing hormone (CRH) levels at times corresponding with elevated HPA activity, and prior i.c.v. injection of the CRH antagonist, alpha-helical CRH, significantly attenuated elevations in plasma ACTH and B. In addition, alpha-helical CRH pretreatment completely blocked endotoxin-induced changes in plasma CBG in both males and females. These findings support the view that endotoxin-induced HPA activation in the neonate may occur via CRH. PMID- 7987368 TI - Glucocorticoids, but not dopamine, negatively regulate the melanotrophic activity of the rabbit pituitary intermediate lobe. AB - The leporidae (rabbit and hare) pituitary intermediate lobe (IL) differs from that of other mammals by its neuroendocrine regulation. In particular, it is not submitted to the classic dopaminergic inhibitory control, which has been considered as a repressive factor for the expression of glucocorticoid receptors (GR) in the mammalian IL. Hence, the present experiments aimed at examining the rabbit IL for the possible existence of GR. Using both immunocytochemistry and binding studies with (3H)-dexamethasone, we localized GR in the nuclei of IL cells and showed the presence of saturable and high-affinity type II receptor sites, with Kd approximately 3.9 nM. Also, exposure of cultured IL cells to 10 nM dexamethasone (DEX) resulted in the blockade of melanocyte-stimulating hormone (alpha MSH) secretion stimulated by oxytocin (OT). Importantly, the inhibitory effect was reversed by a 100-fold excess of the glucocorticoid antagonist RU 38486. This is the first study which clearly demonstrates in a mammalian IL, namely the rabbit, the presence of functional GR, involved in the negative regulation of the melanotrophic activity of this gland. PMID- 7987369 TI - Simultaneous monitoring of intracerebral release and behavior: endogenous vasopressin improves social recognition. AB - We previously reported that direct osmotic stimulation of the supraoptic nucleus (SON) of rats via a microdialysis probe produces a robust 'rebound' release of endogenous vasopressin (AVP) into the extracellular fluid of this hypothalamic nucleus. We now demonstrate in a combined microdialysis and push-pull perfusion study that this intranuclear release is accompanied by increased AVP release in the septum. Simultaneous monitoring of intranuclear release and behavioral performance in the same animal indicated a significant correlation between the amount of endogenously released AVP and improved social memory based on the olfactory discriminative capacities of adult male rats. This memory improvement was partially blocked by local administration of a AVP V1 receptor antagonist either into the SON or septum. These findings indicate that direct osmotic stimulation of the supraoptic nucleus, which increases intracerebral vasopressin release, improves the acquisition and/or processing of olfactory stimuli. Thus, the endogenous neuropeptide fulfills one of the major criteria for being causally involved as a neurotransmitter/neuromodulator in behavioral performance. PMID- 7987370 TI - Androgen receptor function during undernutrition. AB - Hypothalamo-pituitary inhibition of reproductive function during undernutrition is well known, however, the physiological mechanisms leading to suppression of gonadotrophin secretion are not clear. A variety of studies have indicated that testicular negative feedback on LH secretion is enhanced during food restriction. To evaluate directly the suppression by endogenous androgens on hypothalamic GnRH pulse generator activity during food restriction and examine the mechanism underlying the increased testicular steroidal feedback, we examined (1) circulating bioactive LH (bLH) levels in response to selective cerebral androgen blockade by intraventricular administration of an androgen receptor antagonist (hydroxyflutamide, SCH 16423) and (2) the binding capacity and affinity of androgen receptors in medio-basal hypothalamus, pituitary and prostate during undernutrition of intact mature male rats. Hydroxyflutamide (20 micrograms in 10 microliters vehicle), but not vehicle alone, markedly increased bLH levels in both food restricted and ad-lib fed rats. However, the faster (geometric mean 11.4 vs 27.7 min) and greater (47.2 vs 21.9 ng/ml) increase in bLH level in food restricted compared with ad-lib fed controls demonstrates an enhanced sensitivity to blockade of androgenic negative feedback during undernutrition. Food restriction increased androgen receptor binding capacity in pituitary (3.36 vs 0.77 fmol/mg protein) but not in medio-basal hypothalamus or prostate while binding affinity was unchanged by undernutrition in all 3 tissues. These studies reveal that undernutrition both enhances tonic, androgen receptor-mediated feedback suppression of GnRH secretion and increases in pituitary (but not hypothalamic) androgen receptor numbers to cause inhibition of LH secretion. PMID- 7987371 TI - Glutamate inhibits ingestive behaviour. AB - Male rats treated with reserpine were motionless and ingested only a few of ten consecutive intraoral injections of a 1 M solution of sucrose. While injection of apomorphine, a dopamine agonist, stimulated locomotion and stereotyped sniffing in reserpinized rats, it did not reactivate ingestive responses. The non competitive N-methyl-D-aspartate receptor antagonist MK801, however, stimulated locomotion as well as ingestion suggesting involvement of glutamate in the suppressive effect of resperpine on ingestive responses. A series of experiments was therefore undertaken to investigate the possible physiological role of glutamate in feeding. For this purpose, we used Grill's intraoral intake test, in which the rat is infused intraorally with a sucrose solution and the amount ingested measured. In untreated rats, MK801 dose-dependently facilitated ingestion of the sucrose solution and antagonized inhibition of ingestion by cholecystokinin octapeptide. Administration of cholecystokinin octapeptide or ingestion of sucrose increased the concentration of glutamate in the nucleus of the solitary tract, a brain stem relay transmitting sensory information from the gastrointestinal tract to the forebrain. MK801 was found to bind specifically to this brain area and block the elevation of glutamate and dopamine levels which occurred after treatment with cholecystokinin octapeptide in this neural site. Together these data suggest that dopamine and glutamate may interact within the nucleus of the solitary tract in controlling ingestive behaviour. PMID- 7987372 TI - [Arg8]vasotocin excites neurones in the dorsal vagal complex in vitro: evidence for an action through novel class(es) of CNS receptors. AB - Using extracellular recordings from brainstem slices in vitro, it was demonstrated that a high proportion (38/56) of neurones in the dorsal vagal complex of dioestrus, virgin female rats exhibit an excitatory response to [Arg8] vasotocin (AVT). Pharmacological characterization suggests that these responses cannot be entirely explained by interaction with either of the currently known classes of central receptors for oxytocin (OT) and vasopressin (V1a). Comparison of the responses with those to the OT receptor-specific agonist [Thr4,Gly7]-OT (TGOT), showed that not all neurones that responded to TGOT also responded to AVT (3/27). Furthermore, while the effects of 10(-7) M TGOT could be blocked either by the broad-spectrum antagonist d(CH2)5[d-Tyr(OEt)2,Val4,Cit8]-vasopressin or by the selective OT receptor antagonist d(CH2)5[Tyr(Me)2,Thr4,Orn8,Tyr-NH2(9)] vasotocin, these peptides did not completely block the responses to AVT, indicating that AVT is unlikely to act through the central OT receptor. The responses to AVT and [Arg8]-vasopressin (AVP) indicated the presence of at least 2 classes of receptor with which these agonists could act. Of 42 neurones tested with both AVP and AVT, none responded to AVP in the absence of a response to AVT, while 7/42 responded to AVT without a response to AVP. This might be explained by AVP acting through only the V1 receptor, while AVT acts through both the V1 and its own novel class of receptor. This was substantiated by the fact that two OT/V1 receptor antagonists, d(CH2)5[d-Tyr(OEt)2,Val4,Cit8]-VP and d(CH2)5[Tyr(Me)2,Tyr-NH2(9)]-AVP, were unable to block completely all the responses to AVT at a dose which suppressed responses to both AVP and TGOT.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7987373 TI - Testosterone implants in specific neural sites activate female sexual behaviour. AB - Sexual behaviour in most female mammals is regulated by oestrogen, often acting synergistically with progesterone. Moreover, the most important neural site of action for oestradiol is the ventromedial nucleus. In the female musk shrew, Suncus murinus, testosterone (T) activates sexual behaviour. Virgin females first engage in copulatory behaviour many hours in advance of follicular development and ovulation, when plasma oestradiol levels are very low. Testosterone, produced by the ovaries and the adrenal glands, must be aromatized centrally to oestradiol to initiate sexual behaviour. To identify the neural sites of action for T, ovariectomized females received unilateral hormone implants containing testosterone propionate. Hormone pellets were placed in 1 of several brain sites including the medial preoptic area and the dorsalmedial hypothalamus (DMH). Implants in either of these 2 sites, but not in the lateral preoptic area, internal capsule, nor anterior hypothalamus stimulated the induction of sexual behaviour. Hormone implants in the ventrolateral hypothalamus resulted in partially receptive animals. Immunocytochemistry was employed to determine which steroid receptors were present in the 2 behaviourally active sites. The medial preoptic area (MPO) and the dorsal and ventromedial hypothalamus both contain many cells that express oestrogen receptor immunoreactivity. A smaller subset of neurons in these regions are immunoreactive for androgen receptors. In summary, testosterone can act specifically in either the MPO or the DMH to induce female sexual behaviour. Both sites contain cells that express oestrogen and androgen receptors. Thus, testosterone may work via one or both of these steroid receptors to regulate behaviour.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7987374 TI - Involvement of the bed nucleus of the stria terminalis in tonic regulation of paraventricular hypothalamic CRH and AVP mRNA expression. AB - The bed nucleus of the stria terminalis (BNST) occupies a central position in pathways regulating hypothalamo-pituitary-adrenocortical (HPA) stress regulation. The potential role of the BNST in tonic neural control of HPA function was assessed by examining effects of selective BNST lesions on expression of ACTH secretagogues in HPA-integrative neurons of the medial parvocellular paraventricular nucleus. Anterior BNST lesions (ABN) involved major portions of the anteromedial, anterolateral, ventromedial, ventrolateral, dorsolateral and juxtacapsular subnuclei. These lesions resulted in significant (30%) decreases in corticotropin-releasing hormone (CRH) mRNA expression across the rostrocaudal extent of the medial parvocellular PVN, with no accompanying changes in basal arginine vasopressin (AVP) mRNA levels. Posterior BNST (PBN) lesions involved large but subtotal damage to the posterior intermediate, posterior medial, posterior lateral and preoptic subnuclei; these lesions resulted in small but significant changes in CRH mRNA and slight increases in number of AVP mRNA producing parvocellular neurons. PBN effects on CRH mRNA expression were most pronounced at the caudal extent of the medial parvocellular zone, suggesting a topographic input from the posterior BNST to the PVN that is only partially compromised by PBN lesions. Analysis of individual cases revealed a correlation between damage of the anterolateral BNST and decreased CRH mRNA levels, and damage of the posterior intermediate and/or posterior medial BNST and increased CRH mRNA levels. The results suggest differential BNST input into HPA regulation, perhaps reflecting the diversity of limbic input into the BNST region. PMID- 7987375 TI - Bicuculline methiodide influences the central nervous system to produce hyperglycemia in rats. AB - The influence of bicuculline methiodide (BMI), a gamma-aminobutyric acid (GABA) receptor antagonist, on central nervous system regulation of blood glucose homeostasis was studied in fed rats. Injection of BMI (1-10 nmol) into the third ventricle was found to produce hepatic venous hyperglycemia in a dose-dependent manner. This change was associated with increased secretion of epinephrine and glucagon. The role of epinephrine in hyperglycemia was then studied in bilaterally adrenalectomized (ADX) rats injected with BMI. Plasma glucose concentration was found to increase in ADX rats although the level was approximately half that for intact rats and significantly higher than for controls. The increase in epinephrine and glucagon secretion seen in intact rats, but not in ADX rats, suggests BMI induced epinephrine release is responsible for the glucagon secretion. Three possible mechanisms are suggested to account for the rise in plasma glucose in the hepatic vein after injection of BMI: 1) that epinephrine is secreted by the adrenal medulla, 2) that epinephrine secretion stimulates glucagon secretion or 3) that there may be some direct innervation of the liver in rats. PMID- 7987376 TI - Cellular distribution of G protein Go alpha in pituitary lactotrophs: effects of dopamine. AB - Membrane-bound GTP-binding (G) proteins mediate signal transduction in a variety of cell systems. The exact mechanisms of G proteins action are still under investigation but they appear to involve effectors located in the plasma membrane as well as in other parts of the cell. With this study, we investigated the cellular and ultrastructural localization of G protein subunits, and particularly of Go alpha, in normal rat anterior pituitaries and in estrone-induced rat adenomatous lactotrophs. We also evaluated the effects of Go alpha cellular redistribution in rat adenomatous lactotrophs following short-term exposure to dopamine (DA). Using the Protein A-gold (PAG) methodology, Go alpha was found to be present in the cysternae of the endoplasmic reticulum of normal pituitary cells and of adenomatous lactotrophs. In the latter, Go alpha could be co localized with prolactin (PRL). By immunoblots, using specific antisera, significant amounts of Go alpha and Gs42 alpha, together with smaller amounts of Gi alpha, Gs47 alpha and G beta were found to be present in the uncontaminated supernatant fraction of adenomatous lactotrophs. Unexpectedly, exposure of the cells to DA induced a rapid and short-lived decrease in the cytosolic fraction of Go alpha and G beta associated with a decrease of PRL release. Since cytosolic Go alpha can be ADP-ribosylated by pertussis toxin (PT) and is therefore in a heterotrimeric form, our data suggest that the soluble Go protein may play a role during lactotrophs' exposure to an inhibitor of PRL release, perhaps through its relocalization after being internalized with the D2 receptor or by being used for interaction with intracellular and/or membrane-bound effectors. PMID- 7987377 TI - The secretion of alpha-MSH from xenopus melanotropes involves calcium influx through omega-conotoxin-sensitive voltage-operated calcium channels. AB - The secretory activity of endocrine cells largely depends on the concentration of free cytosolic calcium. We have studied the mechanisms that are involved in supplying the calcium necessary for the secretion of alpha-melanophore stimulating hormone (alpha-MSH) from melanotrope cells in the pituitary intermediate lobe of the amphibian Xenopus laevis. Using whole-cell voltage clamp, high-voltage activated calcium currents were observed, with a peak current between 0 and +20 mV. Two types of Ca(2+)-currents appeared, depending on the experimental setup. An inactivating current, which was observed after a 10 msec depolarizing prepulse, resembled currents through N-type channels as it was clearly inhibited by 1 microM omega-conotoxin. The second type was a non inactivating current, which was blocked up to 50% by 1 microM nifedipine, indicating its L-type nature. Only a small component of this inactivating current could be blocked by omega-conotoxin. No evidence was found for the presence of transient, low-voltage activated currents. The spontaneous secretion of alpha-MSH from superfused neurointermediate lobes was dependent on extracellular calcium, as low calcium conditions (10(-4)-10(-8) M) rapidly inhibited this process. Under these conditions, secretion was not affected by depolarizing concentrations of potassium chloride. The calcium ionophore A23187 increased secretion under low calcium conditions, but had no effect on spontaneous alpha-MSH release. These results suggest that spontaneous alpha-MSH release depends on influx of calcium through voltage-operated calcium channels.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7987378 TI - Comparative kinematics of two walking frame gaits. AB - Walking frames are commonly used as part of the gait rehabilitation process for a variety of clinical conditions. There has been little investigation of the characteristics of gait with such frames or of the advantages of one gait style compared with others. The kinematics of two simulated gait patterns with walking frames were investigated using conventional video analysis techniques. The purpose of the study was to compare the two gaits with respect to patterns of joint motion and temporospatial parameters. It was found that simultaneous motion of the protected limb and the frame during stepping (gait S) permitted a faster walking speed than a gait in which the frame and the protected limb were moved separately (gait D). Although the patterns of hip motion in both aided gaits differed markedly from that found in free gait, gait S encouraged more hip extension on the protected side than gait D. Since this is seen as a desirable feature in gait retraining, patients using walking frames, particularly after hip trauma, should be assessed carefully and encouraged to use gait pattern S when possible. PMID- 7987379 TI - Relationship of the pelvic angle to the sacral angle: measurement of clinical reliability and validity. AB - There is a need to better document the reliability and validity of assessment measures used in physical therapy. Studies documenting the reliability of measurement of the pelvic angle and its relationship to sacral motion are presently inconclusive. The purpose of this study was twofold. First, we wanted to determine the reliability and validity of a goniometric measurement of the pelvic angle. We also wanted to test the hypothesis that there is a relationship between the pelvic angle and the sacral angle. Intertester and intratester reliability of goniometric pelvic angle measurements of 23 healthy young adults were examined using three different raters. Radiographic measurements of the pelvic and sacral angle using two raters and goniometric measurement of the pelvic angle using a single rater were taken from 15 patients with low back pain who had been referred for X-rays. Intraclass correlation coefficients (ICCs) of intratester reliability for goniometric measurements of the pelvic angle were .93, .96, and .96. The intertester reliability was .95. The ICCs for intratester reliability for radiological measurements were .92 and .95 for the sacral angle and .98 for both measurements of the pelvic angle. Intertester reliability coefficients were .86 and .88, respectively. The Pearson correlation coefficients for the goniometric and radiological measurements of the pelvic angle were .85 and .68. A comparison of the radiological and goniometric measurements of the pelvic angle with the sacral angle demonstrated low average correlations of .43 and .58, respectively. The results indicate a high level of correlation between and within testers for goniometric measurements of the pelvic angle but only a fair correlation between goniometric and radiological measurements of the pelvic angle.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7987380 TI - The frontal plane relationship of the forefoot to the rearfoot in an asymptomatic population. AB - Physical therapists use biochemical orthotics to treat symptoms attributed to structural abnormalities of the feet. The purpose of this study was to determine the prevalence of forefoot varus, valgus, and neutral positions in a healthy population, and to compare forefoot positions between genders, legs, and age groups. Nonprobability sampling was used to obtain 120 healthy subjects. A repeated-measures, one-group design was used. A forefoot measuring device and a goniometer were used to measure the forefoot-rearfoot frontal plane relationship. Of the 234 measured feet, 86.67% had a varus, 8.75% had a valgus, and 4.58% had a neutral forefoot-rearfoot relationship. No significant difference in position was found between genders or legs within subjects. A certain amount of forefoot varus or valgus may be characteristic of a healthy population; however, future studies should include children and adolescents to determine if forefoot positions are acquired or congenital. PMID- 7987381 TI - Intraobserver and interobserver reliability of asymptomatic subjects' thoracolumbar range of motion using the OSI CA 6000 Spine Motion Analyzer. AB - Because spinal range of motion (ROM) is assessed routinely in clinical and research settings, a technique is needed that can be performed comfortably, quickly, and reliably. The purpose of this study was to determine if ROM data from asymptomatic subjects measured with the OSI CA 6000 Spine Motion Analyzer (OSI SMA) are reliable within and between observers. Thoracolumbar ROM, from approximately T7 to S2, was measured in all three planes in eight male and 13 female asymptomatic adult subjects (mean age = 29.7 years, SD = 5.6; mean height = 1.7 m, SD = 3.4, mean weight = 78.25 kg, SD = 34.6). A standardized protocol was used to fit each subject with appropriate hardware. Foot placement at a comfortable foot angle was standardized by the use of a template. Subjects performed three practice trials of flexion, extension, right and left sidebending, and right and left rotation. During testing, subjects performed four trials of each maximal pain-free motion. The hardware was completely removed and replaced by the same examiner, and ROM trials in all three planes were repeated. The same procedure was completed by a second examiner. Repeated measures analysis of variance and intraclass correlation coefficients (ICC [2,1] were used to analyze intra- and interobserver data. Intraobserver ICCs were 0.89 or higher for all motions. Interobserver ICCs were 0.85 or higher for all motions. Measurements of thoracolumbar ROM using the OSI SMA are sufficiently reliable within and between observers for clinical assessment and research purposes. PMID- 7987382 TI - Influence of hamstring length on the standing position and flexion range of motion of the pelvic angle, lumbar angle, and thoracic angle. AB - Hamstring muscle length may be associated with specific pelvic and trunk postures, but the influence of hamstring length on trunk postures is not well documented. The purposes of this study were to examine the influence of hamstring length on 1) the pelvic angle, lumbar angle, and thoracic angle in standing; and 2) the flexion ranges of motion of the pelvic angle, lumbar angle, and thoracic angle during the toe-touch test. Surface platform pointers over bony landmarks and photography were used to examine the pelvic and trunk angles and ranges of motion of 10 men with short hamstrings, 10 men with medium hamstrings, and 10 men with long hamstrings while standing and after assuming the toe-touch position. Separate one-way analyses of variance detected no significant differences among groups for the three angles in standing. Significant differences were detected among groups for the three angles in the toe-touch position and the flexion ranges of motion during the toe-touch test (p < 0.05). Short hamstrings were associated with decreased flexion range of motion of the pelvic angle and lumbar angle and increased flexion range of motion of the thoracic angle. Therapeutic interventions should be considered in light of the influences of hamstring length on the flexion range of motion of the pelvic angle, lumbar angle, and thoracic. angle. PMID- 7987383 TI - Cuboid plantar and dorsal subluxations: assessment and treatment. AB - Plantar flexion and inversion stresses at the ankle may cause the tarsal cuboid to sublux in a plantar or dorsal direction resulting in pain and impaired joint function. Subluxation of the tarsal cuboid alters the passive physiological motion and accessory glides of the cuboid joints in characteristic patterns of motion restriction. Identification of the pattern of motion restriction is necessary for appropriate diagnosis and treatment. This paper presents the case reports of two patients with lateral foot pain. A subluxed cuboid bone was believed to be the cause of the patient's pain. Assessment and treatment are described and possible pathomechanics for cuboid subluxation are presented. Passive physiological motion of the cuboid and accessory joint glides should be assessed in patients complaining of lateral foot pain or with inversion ankle injuries. Pain and joint impairment can be alleviated with proper assessment and treatment. PMID- 7987384 TI - Fingering fibroblast growth factor receptors. PMID- 7987385 TI - Missense rhodopsin mutation in a family with recessive RP. PMID- 7987386 TI - Parental origin of WT1 mutations and mental retardation in WAGR syndrome. PMID- 7987387 TI - Germline p16 mutations in familial melanoma. AB - The p16 gene is located in chromosome 9p21, a region that is linked to familial melanoma and homozygously deleted in many tumour cell lines. We describe eight p16 germline substitutions (one nonsense, one splice donor site and six missense) in 13/18 familial melanoma kindreds. Six of these mutations were identified in 33/36 melanoma cases in nine families, whereas two were detected in normal controls and are not disease-related. The melanoma-specific mutations were detected in 9p21-linked, but not in 1p36-linked, families, thereby confirming previous reports of genetic heterogeneity. Functional analyses of these mutations will confirm those causally related to the development of familial melanoma. PMID- 7987388 TI - Analysis of the p16 gene (CDKN2) as a candidate for the chromosome 9p melanoma susceptibility locus. AB - A locus for familial melanoma, MLM, has been mapped within the same interval on chromosome 9p21 as the gene for a putative cell cycle regulator, p16INK4 (CDKN2) MTS1. This gene is homozygously deleted from many tumour cell lines including melanomas, suggesting that CDKN2 is a good candidate for MLM. We have analysed CDKN2 coding sequences in pedigrees segregating 9p melanoma susceptibility and 38 other melanoma-prone families. In only two families were potential predisposing mutations identified. No evidence was found for heterozygous deletions of CDKN2 in the germline of melanoma-prone individuals. The low frequency of potential predisposing mutations detected suggests that either the majority of mutations fall outside the CDKN2 coding sequence or that CDKN2 is not MLM. PMID- 7987389 TI - Familial melanoma and p16--a hung jury. PMID- 7987390 TI - Human artificial episomal chromosomes for cloning large DNA fragments in human cells. AB - We have developed a human artificial episomal chromosome (HAEC) system, based on the latent replication origin of the large herpes Epstein-Barr virus, for the propagation and stable maintenance of DNA as circular minichromosomes in human cells. Individual HAECs carried human genomic inserts ranging from 60-330 kb and appeared genetically stable. An HAEC library of 1,500 independent clones carrying random human genomic fragments with average sizes of 150-200 kb was established and allowed recovery of the HAEC DNA. Our autologous HAEC system, with human DNA cloned directly in human cells, provides an important tool for functional study of large mammalian DNA regions and gene therapy. PMID- 7987391 TI - In and around SNRPN. PMID- 7987392 TI - Deletions of a differentially methylated CpG island at the SNRPN gene define a putative imprinting control region. AB - To determine the molecular basis of Prader-Willi syndrome (PWS) and Angelman syndrome (AS), we have isolated new transcripts from chromosome 15q11-q13. Two novel transcripts located within 300 kilobases telomeric to the small nuclear ribonucleoprotein-associated polypeptide N gene (SNRPN) were paternally expressed in cultured cells, along with SNRPN, defining a large imprinted transcriptional domain. In three PWS patients (two sibs), small deletions remove a differentially methylated CpG island containing a newly described 5' exon alpha of SNRPN, and cause loss of expression for the three imprinted transcripts and altered methylation over hundreds of kilobases. The smallest PWS deletion is familial and asymptomatic with maternal transmission. Our data imply the presence of a paternal imprinting control region near exon alpha. PMID- 7987393 TI - Neomorphic agouti mutations in obese yellow mice. AB - Several dominant mutations of the mouse agouti coat colour gene have pleiotropic effects that include obesity and a yellow coat. The Ay allele is caused by a large deletion that affects the expression of several contiguous genes. We show that three other obesity-associated agouti mutations, Aiy, Asy and Avy, are due to different molecular alterations that result in ubiquitous expression of a chimaeric RNA that encodes a normal agouti protein. The Aiy and Avy alleles are caused by insertion of an intracisternal A particle element 1 kb or 100 kb, respectively, upstream of agouti coding sequences. These results provide a model for other genes that show allele-specific imprinting, and demonstrate that molecular mechanisms typically responsible for activation of proto-oncogenes can also lead to other disease phenotypes. PMID- 7987394 TI - p53-deficient mice are extremely susceptible to radiation-induced tumorigenesis. AB - Mice constitutively lacking alleles of the p53 tumour suppressor gene spontaneously develop lymphomas and sarcomas. We report here that a single dose of 4 Gy radiation dramatically decreases the latency for tumour development in p53 heterozygous mice. The pattern of genetic alterations at the remaining wild type allele in these tumours differs substantially from spontaneous tumours from similar mice indicating that p53 itself may have been a target for radiation induced alterations. Lower dose irradiation (1 Gy) of preweanling p53 null mice also significantly decreases tumour latency, suggesting that there are additional genetic targets involved in radiation-induced malignancy. Thus p53-deficient mice provide a sensitive model system for studies of the consequences of radiation exposure. PMID- 7987395 TI - A radiation hybrid map of 506 STS markers spanning human chromosome 11. AB - We present a high resolution radiation hybrid map of human chromosome 11 using 506 sequence tagged sites (STSs) scored on a panel of 86 radiation hybrids. The 506 STSs fall into 299 unique positions (average resolution of about 480 kilobases (kb)) that span the whole chromosome. A subset of 260 STSs (143 positions) form a framework map that has a resolution of approximately 1 megabase between adjacent positions and is ordered with odds of at least 1,000:1. The centromere was clearly defined with pericentric markers unambiguously assigned to the short or long arm. The map contains most genes (125) and expressed sequence tags (26) currently assigned to chromosome 11 and more than half of the STSs are polymorphic microsatellite loci. These markers and the map can be used for high resolution physical and genetic mapping. PMID- 7987396 TI - Identification of mutations in the alpha 3(IV) and alpha 4(IV) collagen genes in autosomal recessive Alport syndrome. AB - Alport syndrome (AS) is an hereditary disease of basement membranes characterized by progressive renal failure and deafness. Changes in the glomerular basement membrane (GBM) in AS suggest that the type IV collagen matrix, the major structural component of GBM, is disrupted. We recently isolated the genes for two type IV collagens, alpha 3(IV) and alpha 4(IV), that are encoded head-to-head on human chromosome 2. These chains are abundant in normal GBM but are sometimes absent in AS. We screened for mutations in families in which consanguinity suggested autosomal recessive inheritance. Homozygous mutations were found in alpha 3(IV) in two families and in alpha 4(IV) in two others, demonstrating that these chains are important in the structural integrity of the GBM and that there is an autosomal form of AS in addition to the previously-defined X-linked form. PMID- 7987397 TI - An autosomal locus causing autoimmune disease: autoimmune polyglandular disease type I assigned to chromosome 21. AB - Autoimmune polyglandular disease type I (APECED) is an autosomal recessive autoimmune disease characterized by a variable combination of the failure of the endocrine glands. The pathogenesis of this unique autoimmune disease is unknown; unlike many other autoimmune diseases, APECED does not show association to specific HLA haplotypes. Unravelling the APECED locus will identify a novel gene outside the HLA loci influencing the outcome of autoimmune diseases. We have assigned the disease locus to chromosome 21q22.3 by linkage analyses in 14 Finnish families. Linkage disequilibrium studies have significantly increased the informativeness of the analyses and helped to locate the critical DNA region for the APECED locus to just 500 kilobases, a much more precise definition than linkage analyses alone could achieve. PMID- 7987398 TI - Length of uninterrupted CGG repeats determines instability in the FMR1 gene. AB - Analysis of 84 human X chromosomes for the presence of interrupting AGG trinucleotides within the CGG repeat tract of the FMR1 gene revealed that most alleles possess two interspersed AGGs and that the longest tract of uninterrupted CGG repeats is usually found at the 3' end. Variation in the length of the repeat appears polar. Alleles containing between 34 and 55 repeats, with documented unstable transmissions, were shown to have lost one or both AGG interruptions. These comparisons define an instability threshold of 34-38 uninterrupted CGG repeats. Analysis of premutation alleles in Fragile X syndrome carriers reveals that 70% of these alleles contain a single AGG interruption. These data suggest that the loss of an AGG is an important mutational event in the generation of unstable alleles predisposed to the Fragile X syndrome. PMID- 7987399 TI - Linkage of the gene for Wolfram syndrome to markers on the short arm of chromosome 4. AB - Wolfram syndrome is an autosomal recessive disorder defined by the occurrence of diabetes mellitus and progressive bilateral optic atrophy. Wolfram syndrome homozygotes develop widespread nervous system abnormalities; in particular, they exhibit severe behavioural difficulties that often lead to suicide attempts or psychiatric hospitalizations. The Wolfram syndrome gene also predisposes heterozygous carriers to psychiatric disorders, and may contribute significantly to the overall burden of psychiatric illness. Based on a linkage analysis of 11 families segregating for this syndrome using microsatellite repeat polymorphisms throughout the human genome, we found the Wolfram syndrome gene to be linked to markers on the short arm of human chromosome 4, with Zmax = 6.46 at theta = 0.02 for marker D4S431. PMID- 7987400 TI - Mutations in the fibroblast growth factor receptor 2 gene cause Crouzon syndrome. AB - Crouzon syndrome is an autosomal dominant condition causing premature fusion of the cranial sutures (craniosynostosis) and maps to chromosome 10q25-q26. We now present evidence that mutations in the fibroblast growth factor receptor 2 gene (FGFR2) cause Crouzon syndrome. We found SSCP variations in the B exon of FGFR2 in nine unrelated affected individuals as well as complete cosegregation between SSCP variation and disease in three unrelated multigenerational families. In four sporadic cases, the normal parents did not have SSCP variation. Finally, direct sequencing has revealed specific mutations in the B exon in all nine sporadic and familial cases, including replacement of a cysteine in an immunoglobulin-like domain in five patients. PMID- 7987402 TI - Ethnic variation in the CYP2E1 gene: polymorphism analysis of 695 African Americans, European-Americans and Taiwanese. AB - Human cytochrome P4502E1 (CYP2E1) is inducible by ethanol and is involved in metabolism of many known carcinogens including N-nitrosodimethylamine, butadiene, benzene, and carbon tetrachloride. A 50-fold variability in CYP2E1 enzyme activity in humans has been observed but it is unknown whether the basis for this variation is genetic or environmental. Recently, two restriction fragment length polymorphisms (RFLPs) within the CYP2E1 gene have been suggested as genetic markers of risk for cancer. The first was a Rsa I polymorphism in the 5' regulatory region that appeared to alter transcriptional activation of the gene and the second was a Dra I polymorphism located approximately 7000 bp downstream in an intron. Rare alleles at each of these loci have been associated with a reduced risk for lung cancer in Japanese and Swedish populations. We have used a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method to determine the genotype frequency for each of these CYP2E1 RFLPs in 695 individuals of Taiwanese, African-American or European-American background. Genotype and allele frequencies for Taiwanese were significantly different from those of African-Americans and European-Americans at either Rsa I or Dra I sites (p < 0.0001). Allele frequencies for African-Americans and European-Americans were significantly different at the Rsa I site (p = 0.03). The rare alleles (c2 and C) occurred at frequencies of 0.28 and 0.24 in Taiwanese, 0.01 and 0.08 in African-Americans, and 0.04 and 0.11 in European-Americans. In addition, we describe three haplotypes common to all three population samples and a fourth haplotype that was only detected in the Taiwanese population sample. This fourth haplotype may have been caused by a recombination event between these markers.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7987401 TI - Noninvasive tests of CYP3A enzymes. PMID- 7987403 TI - Carbamazepine and cigarette smoking induce differentially the metabolism of codeine in man. AB - The inducibility of codeine metabolism by carbamazepine (CBZ) and cigarette smoking has been investigated. A single oral dose of 25 mg of codeine was given to seven epileptic patients before and after 3 weeks' regular CBZ treatment (400 600 mg per day). Codeine was also given to nine volunteers who were heavy smokers (20 cigarettes per day) and to nine non-smokers as controls. All subjects were found to be extensive metabolizers of codeine by O-demethylation. Urine was collected over 8 h following codeine intake. Codeine and the metabolites were analysed with HPLC. CBZ significantly increased the urinary excretion of the N demethylated metabolite, norcodeine (NC) which led to a significant decrease in the metabolic ratio (MR) for N-demethylation. The O-demethylation was not significantly altered. The excretion of normorphine, an active metabolite formed through both O- and N-demethylation of codeine increased by almost three-fold after CBZ treatment. Contrary to CBZ treatment, cigarette smoking slightly but significantly induced the glucuronidation of codeine as shown by a decreased MR for glucuronidation in the smokers, while the O- and N-demethylations were not significantly changed as indicated by the similar MRs in smokers and in non smokers. These results suggest that CBZ and cigarette smoking selectively induce different metabolizing enzymes. The polymorphic O-demethylation is relatively stable to these factors. PMID- 7987404 TI - Low activity of dapsone N-hydroxylation as a susceptibility risk factor in aggressive bladder cancer. AB - N-arylamines involved in the pathogenesis of bladder cancer, require metabolic activation via N-hydroxylation. The efficiency of in vivo N-hydroxylation of dapsone, a non-carcinogenic arylamine, may, therefore, provide a host susceptibility measure of risk of developing bladder cancer. To investigate this possibility, the dapsone recovery ratio, a phenotypic measure of the efficiency of dapsone hydroxylation, has been measured in a case control study in an urban UK population, comparing patients with aggressive bladder cancer (n = 33), non aggressive bladder cancer (n = 60) and controls (n = 108). Dapsone recovery ratio in controls exhibited a unimodal distribution. Patients with aggressive bladder cancer had a similar distribution but significantly lower mean value (p < 0.005). Logistic regression analysis, controlling for sex, age, smoking habit and alcohol consumption confirmed a significant (p < 0.05) association between the dapsone recovery ratio and aggressive bladder cancer. Subjects in the lowest tertile of dapsone recovery ratio had a relative risk to 5.4-fold greater than subjects in the upper tertile (p < 0.009), and a trends test was significant (p < 0.001). There was no significant association between dapsone recovery ratio and non aggressive bladder cancer. These results do not support the hypothesis that the drug metabolizing enzymes involved in dapsone N-hydroxylation are involved in causing bladder cancer. Instead, they suggest the opposite, the observation that low enzyme activity was associated with increased risk is consistent with this enzyme providing a detoxification mechanism for environmental procarcinogens. PMID- 7987405 TI - The influence of environmental and genetic factors on CYP2D6, CYP1A2 and UDP glucuronosyltransferases in man using sparteine, caffeine, and paracetamol as probes. AB - The impact of gender, use of oral contraceptive steroids (OCS), coffee consumption and of smoking on the metabolism of sparteine, caffeine, and paracetamol was studied in 194 randomly selected subjects (98 male and 95 female). Thirty-eight of the male volunteers were cigarette smokers, 40 of the female subjects were smokers and/or users of OCS. The metabolic ratio of sparteine oxidation (MRs) showed a trimodal distribution. 7.7% of the subjects had a MRs > 20 and thus were poor metabolizers (PMs). Within the extensive metabolizer (EM) subjects, a distinct subgroup accounting for 11% was observed with 20 > MRs > 1.2. Six of the 15 phenotypical PMs were heterozygous EMs by genotyping. This indicates the existence of one or several CYP2D6 mutations which cannot be identified by the currently employed genotyping methods. In each subgroup, i.e. smokers/OCS and non-smokers/non-OCS, the cumulative frequency distribution of the heterozygous (wt/B) phenotype caused a shift to higher MRs compared with the wild-type homozygotes (wt/wt). Thus, for the in vivo activity of CYP2D6, genetic determinants prevail over environmental factors. Smoking, use of oral contraceptive steroids, caffeine consumption, or gender had no influence on sparteine metabolism. The distribution of the paracetamol glucuronide/paracetamol metabolic ratio appeared to be unimodal although skewed. Glucuronidation capacity was clearly affected by gender, OCS use and smoking. It was higher in male than in female subjects. Male smokers had the highest, and female non-smokers/non-OCS users the lowest metabolic ratio. CYP1A2 activity, as determined by a caffeine metabolic ratio ((AFMU + 1X + 1U)/1, 7U), was multimodally distributed and was clearly increased in smokers. It was significantly correlated to paracetamol glucoronidation in male heavy smokers (r=0.85), suggesting an element of co-regulation of CYP1A2 and of paracetamol conjugating UDP-glucuronosyltransferase isozymes, including UGTI.6. PMID- 7987406 TI - Characterization of Ah receptor promoter in human liver cell line, HepG2. PMID- 7987407 TI - No difference in substrate affinity of plasma dipeptidyl carboxypeptidase-1 encoded by the I and D allelic forms of its gene. PMID- 7987408 TI - Circadian clock- and phytochrome-regulated transcription is conferred by a 78 bp cis-acting domain of the Arabidopsis CAB2 promoter. AB - The Arabidopsis CAB2 promoter was used to define the terminal genomic targets that are subject to regulation by the circadian clock. An in vivo cab::luciferase bioluminescent marker was used to enable the assaying of the expression of chimeric constructs with unprecedented sensitivity and time resolution in living seedlings. Dissection of -322 to +1 of the CAB2 promoter has revealed several interesting features: it was demonstrated that the 323 bp fragment contains at least one strong general positive element. The positive element contains an ACGT core sequence specifically bound by a protein activity, termed CUF-1, and contributes to high level expression but is not required for phytochrome- or circadian-regulation. Moreover, a 78 bp domain was defined that confers both circadian- and phytochrome-regulation upon heterologous promoters. Conserved GATA sequences within the 78 bp regulatory domain are specifically bound by a protein factor designated CGF-1. The binding specificity of CGF-1 appears to be related to the GT-family of trihelix DNA-binding proteins. The role of these DNA-protein interactions is discussed in terms of clock- and phytochrome regulation, and their relevance as targets for pathways defined by photomorphogenic mutants. PMID- 7987409 TI - Function of the Chlamydomonas reinhardtii petd 5' untranslated region in regulating the accumulation of subunit IV of the cytochrome b6/f complex. AB - Translational control is an important regulatory mechanism in chloroplasts, and is thought to be mediated by cis-acting elements in the 5' untranslated regions (UTRs) of mRNAs. Chloroplast transformation was used to replace the wild-type Chlamydomonas reinhardtii petD 5' UTR with mutated versions. Transformants containing altered 5' UTRs had either a wild-type photosynthetic phenotype, a leaky non-photosynthetic phenotype, or were unable to grow photosynthetically. Among those transformants with a wild-type phenotype were ones containing mutations in a putative Shine-Dalgarno sequence element. The results indicate that two regions of the 362 nucleotide (nt) 5' UTR may act as positive elements for translation, one located between nt 150 and 200, and the other situated approximately 40 nt upstream of the start codon, at nt 320. In every case where translation was compromised, petD mRNA accumulated to a lower level than in wild type cells, ranging from 15% to 60% in different strains. It was concluded that specific regions of the petD 5' UTR mediate translational activation, and that mRNA stability may be linked to translatability. PMID- 7987410 TI - Segments encoding 5'-untranslated leaders of genes for thylakoid proteins contain cis-elements essential for transcription. AB - The promoter region -118/-29 of the spinach PetH gene encoding the ferredoxin NADP(+)-oxidoreductase contains crucial cis-elements for the regulated expression, while sequences for the 5'-untranslated leader determine the quantitative expression of chimeric GUS gene fusions in transgenic tobacco. Deletion of leader sequences in chimeric GUS gene fusions of the spinach PetE and PsaF genes (for plastocyanin and the subunit III of photosystem I, respectively) results also in a decline in the GUS activity. Appropriate gene constructs and run-on transcription assays demonstrate unambiguously that the leaders of all three genes are involved in transcription rather than in post-transcriptional processes. They appear to contain gene-specific control elements rather than cis determinants for general initiation factors. Expression-relevant segments in the PsaF and PetH leaders contain two CT-rich sequences, designated CT-LB and CT-B, of which at least the former binds to a protein factor in gel mobility shift assays. These motifs are not found in the PetE leader. The findings imply that leader sequences may contain cis-elements that are essential for the transcription, that they influence GUS gene expression quantitatively rather than qualitatively, and that these elements, as those of promoters, can be quite variable in sequence. PMID- 7987411 TI - Identification of loci in Arabidopsis that confer resistance to geminivirus infection. AB - The infection of susceptible plant hosts by single-stranded DNA viruses in the geminivirus group depends on the interaction of host and viral factors for the replication of viral DNA, the expression of viral genes, and the movement of virus throughout the plant. This paper reports that two strains of the geminivirus, beet curly top virus (BCTV) differ in their ability to infect certain ecotypes of Arabidopsis thaliana. Symptoms appeared on susceptible plants approximately 2-3 weeks after inoculation with BCTV-Logan and after 10-15 days with BCTV-CFH. Symptoms were more severe in BCTV-CFH-infected plants and included leaf curling, the formation of stunted, deformed inflorescence structures and the accumulation of anthocyanin pigments in symptomatic tissues. Analysis of viral DNA accumulation indicated that symptom development and severity were correlated with the amount of viral DNA present in the plants. Viral DNA was undetectable in two ecotypes that were phenotypically resistant to BCTV-Logan. Studies of viral DNA replication in excised inflorescence pieces demonstrated that BCTV-Logan could replicate in tissues from these resistant ecotypes, suggesting that resistance was due to a block in viral movement. Genetic studies of these two ecotypes indicate that resistance is due to a single, recessive locus. This is the first example of a single resistance locus to any geminivirus. The identification of resistant and susceptible interactions between different BCTV strains and A. thaliana ecotypes provides an excellent model system for the genetic and molecular analysis of the interaction of a plant host with this important group of plant pathogens. PMID- 7987412 TI - Molecular characterization of a beta-type proteasome subunit from Arabidopsis thaliana co-expressed at a high level with an alpha-type proteasome subunit early in the cell cycle. AB - Proteasomes are the essential components of complexes involved in an extralysosomal energy- and ubiquitin-dependent proteolytic pathway. The first alpha-type proteasome subunit in plants has recently been described. In this work, the sequence of the first beta-type proteasome subunit in plants, isolated from Arabidopsis thaliana cDNA libraries is reported. The mRNA accumulation of both subunits was analysed and compared with those of the ubiquitin and histone mRNAs, in different tissues and during re-initiation of mitotic activity. It is demonstrated that in plants, as in animal cells, the transcripts of both the alpha-type and beta-type proteasome subunits accumulate to high levels during cell proliferation, in parallel with mRNAs coding for a ubiquitin fusion protein and several polyubiquitins, but earlier than those coding for histone H4 whose expression is known to be coupled to DNA synthesis. These results suggest that, as in animal cells, proteasomes may be involved in the progression of the cell cycle. PMID- 7987413 TI - Translation of psbA mRNA is regulated by light via the 5'-untranslated region in tobacco plastids. AB - The plastid psbA gene encodes the 32 kDa D1 polypeptide of photosystem II. It has previously been shown that the initiation of psbA mRNA translation in tobacco is regulated by sequences outside of the coding region. To identify the cis-acting regulatory sequences involved in the translational control, a series of chimeric uidA genes, encoding the beta-glucuronidase (GUS) reporter enzyme, were introduced into the plastid genome. GUS accumulation in response to the light (135- to 200-fold), and the arrest of uidA mRNA translation in light-grown seedlings following transfer for 2 h to the dark, was observed only if the transgenes contained the psbA 5'-untranslated leader region (UTR). Changes in GUS accumulation were accompanied by little or no changes in the uidA mRNA levels. The data indicate that the initiation of D1 translation in tobacco plastids is controlled via the psbA 5'-UTR. PMID- 7987414 TI - Phenotype of the fission yeast cell cycle regulatory mutant pim1-46 is suppressed by a tobacco cDNA encoding a small, Ran-like GTP-binding protein. AB - Mutations in which the onset of mitosis is uncoupled from the completion of DNA replication has recently been described. Characterization of these mutants led to the identification of Pim1/Spi1 in fission yeast and RCC1/Ran proteins in mammalian cells. Their Saccharomyces cerevisae homologues, the MTR1/CNR1 proteins, appear to be involved in controlling RNA metabolism and transport. Here the isolation and partial characterization of plant cDNA clones which encode proteins homologous to the mammalian/fission yeast/budding yeast Ran/Spi/CNR proteins are reported. Higher plants appear to contain more than one gene per haploid genome which codes for Ran proteins. These genes are expressed in different plant tissues, including root tips and stems, known to contain mitotically active cells. The tobacco Ran-like proteins, like their mammalian and yeast homologues, are soluble proteins which are found in the cytoplasm and in the nucleus. In addition, it has been shown that overexpression of the tobacco Nt Ran-A1 cDNA suppressed the phenotype of the temperature-sensitive fission yeast pim1-46 mutant. These results suggest that the plant Ran genes can be functionally equivalent to the mammalian/fission yeast/budding yeast Ran/Spi/CNR genes and that they may play a role: (i) in maintaining a coordinated cell cycle; (ii) in controlling RNA metabolism and transport in higher plants; and/or (iii) in protein import into the nucleus. PMID- 7987415 TI - T-DNA tagging of a seed coat-specific cryptic promoter in tobacco. AB - T-DNA tagging with a promoterless beta-glucuronidase (GUS) gene generated a transgenic Nicotiana tabacum plant that expressed GUS activity only in developing seed coats. Cloning and deletion analysis of the GUS fusion revealed that the promoter responsible for seed coat specificity was located in the plant DNA proximal to the GUS gene. A 3.3 kb fragment corresponding to the insertion site was isolated from untransformed plants. No long open reading frames were detected in this region. Northern blots and RNase protection assays failed to detect transcripts from this region in untransformed plants. Furthermore, the insertion site was situated within the N. tomentosiformis genome of the allotetraploid species N. tabacum, in a region which is not conserved within the genus Nicotiana. It is concluded that seed coat-specific GUS expression in this transgenic plant resulted from T-DNA insertion next to a cryptic promoter. These results suggest that at least some of the fusions generated to marker genes in promoter trapping studies are not associated with conventional gene promoters. The possibility that similar insertion events play a role in gene evolution is discussed. PMID- 7987416 TI - Identification of an enhancer/silencer sequence directing the aleurone-specific expression of a barley chitinase gene. AB - Chitinases are expressed in various plant tissues where they are thought to play a role in defense against chitin-containing pathogens. Transient gene expression assays have been used in tissues of barley to delineate promoter sequences involved in the regulation of an aleurone-specific chitinase gene (Chi26), and of a vegetatively expressed chitinase gene (Chi33). The assays measured the activities of transcriptional fusions between chitinase 5' upstream sequences and GUS reporter genes after DNA delivery by particle bombardment. Analysis of Chi26 5' and 3' promoter deletions indicated that sequences between -200 and -140 confer developmental and aleurone-specific expression. Deletions/replacements covering this part of the promoter indicated that sequences between -179 and -147 (E-region) direct expression in aleurone cells. The ability of the 33bp E-region of the Chi26 promoter to activate transcription specifically in aleurone was confirmed by constructing and testing two types of chimeric promoters. The first type, which contained two copies of the E-region fused to the CaMV 35S TATA box, conferred aleurone-specific expression of a GUS reporter gene. The second type, which contained a single copy of the E-region inserted into a deleted, inactive Chi33 promoter derivative, was also capable of directing transcription in aleurone but not in leaves. The pattern of expression of this and other Chi26/Chi33 chimeric promoters suggest that the E-region contains cis-acting sequences which activate transcription in aleurone and silence transcription in leaves. DNA sequence motifs implicated in the regulation of Chi26 and Chi33 are described. PMID- 7987418 TI - Acute low back problems in adults: assessment and treatment. Agency for Health Care Policy and Research. AB - This Quick Reference Guide for Clinicians contains highlights from the Clinical Practice Guideline version of Acute Low Back Problems in Adults, which was developed by a private-sector panel of health care providers and consumers. The Quick Reference Guide is an example of how a clinician might implement the panel's findings and recommendations on the management of acute low back problems in working-age adults. Topics covered include the initial assessment of patients presenting with acute low back problems, identification of red flags that may indicate the presence of a serious underlying medical condition, initial management, special studies and diagnostic considerations, and further management considerations. Instructions for clinical testing for sciatic tension, recommendations for sitting and unassisted lifting, tests for identification of clinical pathology, and algorithms for patient management are included. PMID- 7987417 TI - Toward cataloguing all rice genes: large-scale sequencing of randomly chosen rice cDNAs from a callus cDNA library. AB - A large-scale sequence analysis of rice cDNA was performed for a library from rice callus cultured in a medium containing 1 p.p.m. of 2,4-dichlorophenoxyacetic acid. Random sequencing of 2778 cDNA clones generated 2259 non-redundant expressed sequence tags (ESTs). The strategy of sequencing cDNAs can yield quickly a large number of novel genes. After translation, 690 sequences showed a significant amino acid sequence similarity to sequences already known from PIR. The source of known proteins ranged from bacteria to human. In this report, the non-redundant set of 280 identified ESTs is analyzed in detail. PMID- 7987419 TI - IV joint meeting of Hungarian, Italian and Polish Pharmacological Societies. Poznan, September 19-21, 1994. Abstracts. PMID- 7987420 TI - Dynamic intensity variations of individual choral singers. AB - Twenty adult singers from one choral group were asked to produce sustained vowels and a short hymn sample while using three different dynamic levels: pianissimo, mezzoforte, and fortissimo. Large differences were found in total dynamic range among the subjects. Sustained vowels were slightly higher in output than was a song sample. Mezzoforte levels were produced closer to fortissimo than to pianissimo. When the individual results were combined mathematically, the average levels of the singers were consistent with earlier data from other choral groups. Implications for "choral blend" are discussed. PMID- 7987421 TI - Acoustic and physiologic factors in duet singing: a pilot study. AB - Ensemble singing has recently received increased attention by voice scientists. From the literature, it appears that singing in groups requires techniques that are different from those used in solo singing. This experiment studied the characteristics of a pair of male vocalists who were recorded as they sang two duet scores. Analysis of the results showed that timing, pitch, loudness, and long-term average spectra characteristic of both solo and ensemble singing were employed. The use of solo versus ensemble techniques may be more a function of musical style rather than the number of individuals who sing in a group. PMID- 7987423 TI - Interference between normal vibrato and artificial stimulation of laryngeal muscles at near-vibrato rates. AB - A stabilized tremor hypothesis for vocal vibrato is investigated. The stabilizer is assumed to be a mechanical oscillator that may contain reflex loops. Artificial stimulation of the cricothyroid muscle in one subject showed a well defined resonance curve of this peripheral oscillator at approximately 5.0 Hz. Combined artificial stimulation with natural vibrato showed that the vibrato could be entrained by a peripheral stimulus, provided the two frequencies are separated by no more than approximately +/- 0.5 Hz. This suggests that vibrato frequencies are not "hard-wired" centrally, even though a collection of centrally generated tremors may serve as excitation to the peripheral oscillator. PMID- 7987422 TI - The perceptual features of vocal fatigue as self-reported by a group of actors and singers. AB - Performers (10 actors/10 singers) rated via a self-report questionnaire the severity of their voice-related changes when vocally fatigued. Similar frequency patterns and perceptual features of vocal fatigue were found across subjects. Actors rated "power" aspects (e.g., voice projection) and singers rated vocal dynamic aspects (e.g., pitch range) of their voices as most affected when vocally fatigued. Vocal fatigue was evidenced by changes in kinesthetic/proprioceptive sensations and vocal dynamics. The causes and context of vocal fatigue were vocal misuse, being "run down," high performance demands, and using high pitch/volume levels. Further research is needed to delineate the perceptual features of "normal" levels of vocal fatigue and its possible causes. PMID- 7987424 TI - Modulation of fundamental frequency by laryngeal muscles during vibrato. AB - The variations in voice fundamental frequency (F0) that occur during vibrato production may be produced, at least in part, by modulation of laryngeal muscle activity. We have quantified this relation by using a cross-correlation analysis of the changes in F0 during vibrato and the changes either in motor unit firing rate or in gross electromyographic activity from the cricothyroid (CT) and the thyroarytenoid (TA) muscles. Two trained amateur tenors provided the data. Correlations were generally quite strong (mean r for the CT was 0.72 for singer 1 and 0.50 for singer 2; mean r for the TA was 0.31 for singer 2), thus providing support for previous evidence that fundamental frequency modulation in vibrato involves active modulation of the laryngeal motoneuron pool, especially by the CT muscle. In addition, phase delays between muscle modulation and changes in fundamental frequency were substantial (averaging approximately 130 degrees for the CT and 140 degrees for the TA). This finding may help provide insight regarding the mechanisms responsible for the production of vibrato. PMID- 7987425 TI - Relations between voice range profiles and physiological and perceptual voice characteristics in ten-year-old children. AB - Pitch and intensity range of 60 children were recorded and plotted in voice range profiles (VRPs). Different aspects were investigated: minimum phonation threshold, pitch range, and maximum dynamic range. Vocal fold status was determined via laryngoscopic examination. Ten percent of the children had vocal nodules, 23% glottal chinks. Seven voice experts listened to the voices recorded on two separate occasions and rated their properties along 16 parameters including hoarseness. Fourteen percent were rated as hoarse on both recordings and were thus classified as being chronically hoarse. Departures from normal in VRP characteristics were found for children suffering from chronic hoarseness, nodules, and glottal chinks. Children in general seem to have somewhat compressed VRP contours compared with adults, reflecting restricted dynamic vocal capabilities; however, children with mutational voices exhibited an approximation to adult upper VRP contours. PMID- 7987426 TI - Comparison of maximum flow declination rate: children versus adults. AB - The measure of maximum flow declination rate (MFDR) and location of MFDR provided information regarding the laryngeal mechanism's response to vocal intensity variation as a function of gender and age. Results indicate (a) increases in MFDR values as vocal intensity increases for both children and adults, and (b) higher MFDR values for men versus women and children; no gender difference was found for the children. Results for location of MFDR indicate (a) the location of MFDR to be highest for the loud-intensity production as compared with soft- and comfortable-intensity productions, and (b) the location of MFDR in women to be higher than in men. No gender difference was found for the children. PMID- 7987427 TI - Foreperiod duration, range, and ordering effects on acoustic LRT in normal speakers. AB - One quantitative measure of vocal motor control is phonation onset latency relative to presentation of an external stimulus in a reaction time task. However, variables within the design of reaction time experiments can affect laryngeal reaction time (LRT) values. The present study examines effects of foreperiod characteristics on LRT for normal speakers. Foreperiod is the interval between presentation of warning and response cues. LRT was affected by absolute foreperiod duration, by the average foreperiod duration of a block of trials, and by the ordering and range of foreperiods within a block of trials. Results are discussed with respect to foreperiod effects on the subjective expectancy and objective probability of occurrence of the response cue and on the timing of neurophysiologic processes. Control of subjective effects is critical to assessment of neurophysiologic constraints on LRT. PMID- 7987429 TI - Average loudness level, mean fundamental frequency, and subglottal pressure: comparison between female singers and nonsingers. AB - Subglottal pressure, measured indirectly as the oral pressure during /p/ occlusion, was studied in 10 classically trained female singers and 10 female nonsingers, as they uttered the syllable /pa/ as softly and as loudly as possible over their entire voice ranges. There were no discernible differences between the subject groups for soft vowel phonation, but for the loudest vocalizations the singers used considerably higher subglottal pressures. Possible reasons for this difference are discussed. PMID- 7987428 TI - Improvements in estimating the harmonics-to-noise ratio of the voice. AB - An improved algorithm for computing harmonics-to-noise ratio (HNR) of the voice was developed and tested using synthesized vowels at various fundamental frequencies and known HNR values. The described algorithm implements a stringent routine for the identification of pitch pulse boundary markers based on a combination of peak-picking and zero-crossing procedures. Results showed mean absolute errors between computed versus expected HNR to be < 2 dB, a significant improvement over previously reported methods. Computational errors were minimized most effectively with vowel samples in the range of 17 to -10 dB HNR. Normative data for young adult males and females indicate that HNR < 13 dB may be considered abnormal in a majority of cases. PMID- 7987430 TI - Efficacy of vocal function exercises as a method of improving voice production. AB - Objective voice analysis including acoustic, aerodynamic, and laryngeal videostroboscopic measures demonstrated normal voice in 35 adult women. The subjects were then randomly divided into experimental, placebo, and control groups. The experimental group engaged in vocal function exercises. The placebo group engaged in a placebo exercise program. Objective measures taken after 4 weeks of execise demonstrated significant changes in phonation volume, flow rate, maximum phonation time, and frequency range for the experimental group. No significant changes were noted in the measurements of the control and placebo groups. PMID- 7987431 TI - Does the voice improve with vocal hygiene education? A study of some instrumental voice measures in a group of kindergarten teachers. AB - This study investigated the efficacy of a program of vocal hygiene education designed for an occupational group at risk for dysphonia, namely, kindergarten teachers. Twelve female teachers explored concepts and knowledge of vocal abuse and vocal hygiene in a workshop session and attempted to practice vocal hygiene for 2 months. They showed significant voice improvement as assessed instrumentally in terms of three acoustic and electroglottographic parameters. There was no significant change of voice in a control group of 13 teachers. The results suggest that teachers were able to improve their voices if they significantly reduced vocal abuses in daily life and practiced specific strategies to maintain classroom order and reduce the use of voice in teaching. PMID- 7987433 TI - Prosthetic ligaments in ACL reconstruction. PMID- 7987432 TI - Muscle disease symptoms: evaluation and significance. PMID- 7987434 TI - The antiphospholipid antibody syndrome: new pieces to the puzzle. AB - Recent data strongly suggest that "antiphospholipid" autoantibodies are directed against a variety of phospholipid-binding plasma proteins including beta 2GPI, prothrombin, factor Xa, protein C, and protein S. Further characterization of the spectrum of antibody specificity and affinity in individual patients may explain the varied clinical presentations associated with aPLs. The next several years hold great promise for a better understanding of the pathophysiology of the aPL syndrome and the precise role of aPLs in the pathogenesis of thrombosis and recurrent fetal loss. PMID- 7987435 TI - [Surveillance of pregnant women without social insurance: an ethical and reasonable necessity]. PMID- 7987436 TI - [Evaluation of somatotropin function in children with short stature: an often difficult task]. PMID- 7987437 TI - [Is the transfusion safety a myth?]. PMID- 7987438 TI - [Effects of refeeding on serum immunoglobulin (IgA, IgG, IgM) concentrations in children with severe protein-energy malnutrition]. AB - BACKGROUND: Published studies on the serum immunoglobulin concentrations of patients with protein-energy malnutrition (PEM) have been contradictory. This report describes such a study in 21 Senegalese children. POPULATION AND METHODS: Twenty one Senegalese infants (mean age: 19 +/- 2 months) with severe PEM were included in the study. Their weight was less than 32% of the normal range-for height and all had sparse, thin hair and dyspigmentation of the skin. They were all suffering from hypoproteinemia (less than 70% of normal) and hypoalbuminemia (less that 61% of normal). The presence or absence of edema, loss of subcutaneous fat and mental changes were used to classify them into three groups. 1) kwashiorkor: eight infants; 2) marasmus: eight infants; 3) kwashiorkor plus marasmus: five infants. The control group comprised 27 infants living in the same area and having the same dietary habits as the 21 sick infants. The 21 infants with malnutrition were refed for 3 weeks with a diet supplying 100-150 Kcal/kg/d and 5-8 g/kg/d protein. The plasma concentration of proteins, prealbumin and immunoglobulins was measured on days 0, 8, 15 and 21. RESULTS: The only significant change was in the IgG concentrations of group 1, which increased to normal levels by day 15 as did the total protein and prealbumin. CONCLUSION: Severe PEM can lead to a loss of one class of immunoglobulins, but this can be restored by refeeding. PMID- 7987439 TI - [Cytomegalovirus pneumopathies in pediatric intensive care units]. AB - BACKGROUND: Cytomegalovirus (CMV) infection can result in major complications in immunocompromised infants and children. CMV pneumonia may be difficult to diagnose and the true pathogenic role of the virus in the disease is not always clear. This report describes a cohort of 20 children who suffered from CMV pneumonia. POPULATIONS AND METHODS: Twenty children aged 1 month to 11 years 10 months were admitted to our intensive care unit between 1981 and 1990 because of pneumonia with evidence of CMV infection. They were classified into three groups: group I (cases 1-10) with hemopathy or cancer, group II (cases 11-14) with AIDS, and group III (cases 15-20): non immunodeficient or immunosuppressed children. CMV infection was diagnosed after isolation of CMV from bronchoalveolar lavage (BAL) fluid (15 patients), lung biopsy revealing intranuclear inclusions or CMV antigens, or CMV-positive cultures (four patients), CMV-positive urine cultures (one patient). RESULTS: Clinical manifestations and X-rays findings were unspecific; interstitial pneumonia was found only in immunodeficient patients. CMV pneumonia was diagnosed only in two patients on post mortem examination. Concomitant pneumocystis carinii was found on BAL in two patients (group I) and two others (group II). Thirteen patients required ventilation. Eleven patients were given ganciclovir for 2 or 3 weeks; one of them was given a single dose. This treatment was well tolerated. Mortality was 90% in group I, 100% in group II and 33% in group III. CONCLUSION: Ganciclovir did not appear to benefit the immunocompromised patients with CMV pneumonia. Future treatment should include hyperimmune CMV immunoglobulins plus ganciclovir. Careful hand washing is important for all those caring for these patients to prevent contamination as is the use of CMV-negative blood products. PMID- 7987440 TI - [Anti-Haemophilus influenzae b (Hib) natural immunity in children in Burkina Faso]. AB - BACKGROUND: Natural immunity to Haemophilus infection type b that is acquired by the mothers and passively transmitted to their newborns is not well-known in developing countries, where the frequency of Haemophilus meningitis in infancy is high. POPULATION AND METHODS: Blood samples (5 ml) were taken from 89 women at the time of delivery and from the cord of their babies. Blood samples were also taken from 290 infants and children, distributed into nine subgroups as a function of their age. Children with protein-calorie malnutrition and immune deficiency were excluded from the study. Antibodies against Haemophilus influenzae were measured by Elisa and radioimmunologic methods. Blood concentrations of 0.15 pg/ml or more were considered to be protective. RESULTS: All the blood samples of mothers and cords contained protective levels of antibodies, as did the samples from 30% of those infants aged 0-60 days (all the infants were less than 1 month). No infant in the subgroup 12-23 months had protective levels of antibodies. The incidence of Haemophilus meningitis was correlated with the absence of antibodies. CONCLUSION: Maternal immunity is gradually lost by babies during their first 2 months of life, earlier than in developed countries. Early vaccination, at 3 months of age, is mandatory. PMID- 7987441 TI - [Contribution of genetic typing for the diagnosis of familial adenomatous polyposis in pediatrics]. AB - BACKGROUND: The gene responsible for familial adenomatous polyposis, (APC), has been recently cloned and genetic map with several polymorphic markers has been established. POPULATION AND METHODS: Blood samples (20 ml) were taken from 34 subjects belonging to four families at risk for familial adenomatous polyposis. Nineteen of these 34, less than 20 years old, had one parent having polyposis or dead because of it. Polyposis was diagnosed, in ten of these 19 by endoscopy. Genomic DNA was extracted from peripheral leukocytes and Southern blot analyses were performed in each family, using RFLPs on both sides of the APC locus. RESULTS: DNA analysis identified normal and mutant haplotypes at the APC locus in each family. It was thus possible to follow the segregation of mutant alleles. These results were compared with the anamnestic and endoscopic data. Bearing in mind the risk of recombination when using extragenic markers, RFLPs allowed early diagnosis of APC in pre and/or asymptomatic patients. CONCLUSIONS: Genetic analysis can be used to diagnose APC in affected families, provided the risk of recombination is taken into account. Intragenic microsatellites markers will soon be available. These will provide more information on the APC gene, and hence direct molecular diagnosis of APC. PMID- 7987442 TI - [Anaphylactic shock and low osmolarity contrast medium]. AB - BACKGROUND: Low osmolality contrast media are generally better tolerated than those with high osmolality. This report describes a case of severe collapse after injecting a low osmolality contrast medium. CASE REPORT: A 15 month-old girl with aortic arch abnormalities was admitted for investigation under general anesthesia. She had a history of allergy but had not previously been exposed to contrast medium. She was given ioxaglate (2 mg/kg) into an artery. The infusion immediately resulted in generalized erythema, tachycardia, hypotensive collapse and ECG abnormalities. The patient was immediately given adrenaline, vasopressive drugs, corticosteroids and plasma protein fraction, which led to a rapid recovery. The ductus arteriosus was ligated a few days later without complications despite the application of iodine to the skin and the use of anesthetic drugs. CONCLUSION: An unpredictable adverse reaction to low osmolality contrast medium can occur. Risk factors must be identified and immediate arrangements made for resuscitation. PMID- 7987443 TI - [Successful treatment of chronic active hepatitis with high-dose intravenous immunoglobulins in agammaglobulinemia]. AB - BACKGROUND: Rapid progression of chronic active hepatitis can occur in patients with hypogammaglobulinemia. This report describes the successful use of i.v. immunoglobulins to treat chronic hepatitis in a child with agammaglobulinemia. CASE REPORT: A 17 month-old boy was admitted because he had suffered from recurrent infections since the age of 6 months. His family history was normal. Clinical and laboratory investigations showed hepatomegaly, agammaglobulinemia with absence of IgG, IgA, IgM and IgE, absence of beta cells, normal T cells, normal T cell proliferation and normal levels of complement, elevated ALAT (70 and 200 IU/ml) and ASAT (60 and 188 IU/ml). Liver biopsy showed typical features of chronic active hepatitis. The cause of this hepatitis (B and C virus, EBV, autoimmune markers) was not found. The patient was first given gammaglobulins (80 mg/kg) every week, subcutaneously, for 9 weeks, which did not change his transaminasemia. A second course of gamma-globulins, 400 mg/kg every 3 weeks, intravenously, for 6 months, resulted in a transient normalization of transaminases for 3 months. Definitive normalization was only obtained when the patient was given i.v. gammaglobulins (400 mg/kg/week) which gave a residual level of blood IgG of 10 g/l. This apparent cessation of hepatitis activity was confirmed by a second liver biopsy. The patient is now given i.v. gammaglobulins, twice a month, producing a residual blood IgG concentration of 5 g/l. CONCLUSIONS: The activity of this chronic hepatitis is closely correlated with the residual blood IgG concentration. Gammaglobulins could help neutralize virus extra-cellularly, although the viral origin of this hepatitis has not been demonstrated. PMID- 7987444 TI - [Neurologic Behcet disease]. AB - BACKGROUND: Behcet's disease is very occasionally revealed by neurological abnormalities. This report describes such a case. CASE REPORT: A 13 year-old girl was admitted because of status epilepticus and fever. Clinical examination showed horizontal nystagmus, cerebellar syndrome, right hemiplegia, ophthalmoplegia and meningitis. Her CSF contained 80 lymphocytes/mm3, 0.75 milligram proteins and 0.5 milligram glucose. CT scan showed a hypodense area in the internal capsule. Two similar episodes occurred 4 and 6 months later, but all attempts at determining the etiology were negative. A diagnosis of neurological Behcet's disease was considered 10 months after the first episode when the patient developed oral ulcers followed by pseudofolliculitis of the scalp. The disease recurred several times despite treatment with prednisone, colchicine and antiaggregant drugs. CONCLUSION: Recurrent aseptic meningitis is a classic manifestation of neurological Behcet's disease. It usually appears 2 months to 27 years after the first extraneurological signs and not, as in this case, several months before. PMID- 7987445 TI - [Brain abscess complicating dental caries in children]. AB - Brain abscess following dental or periapical infection is rare in childhood. This report describes brain abscesses found in two children with dental caries. Case 1.--A 12 year-old boy was admitted because he had suffered from acute meningitis for 3 days. Clinical examination showed symptoms of meningitis plus palsy of the right third and fourth cranial nerves and of the left facial nerve, and a defect in the left temporal field. Funduscopic examination showed papilledema; CT scan and MRI showed a ring-shaped lesion in the right occipital area. The patient was given cefotaxime and thiamphenicol. The abscess was drained; bacteriological examination showed Actinomyces viscosus and Peptostreptococcus magnus. The neurological condition and the CT scan lesion improved, but intracranial pressure increased again on the 17th day after the onset, requiring replacement of the antibiotics by rifampicin and ampicillin plus clavulanic acid for 2 months. This brain abscess appeared to be metastatic, derived from the infection of a large dental cyst due to a dental infection that had been treated 6 months earlier. Case 2.--A 8 1/2 year-old girl was admitted because she was suffering from palsy of the left facial nerve and left arm. She had had headaches and fever for a few days. Clinical examination showed the palsies and drowsiness. CT scan showed two brain abscesses. The patient was given ceftriaxone, fosfocin and metronidazole. She had been treated for a gingival abscess 1 month earlier, and had two infected teeth extracted. Improvement of the intracranial pressure was transient and the antibiotics were changed on the 12th day of treatment.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7987446 TI - [Erythrocytosis in a 4 year-old child: diagnostic, prognostic, therapeutical problems]. AB - BACKGROUND: Pure erythrocytosis is rare in children. This report describes such a case. CASE REPORT: A 4 year-old boy was admitted because erythrocytosis had been found routinely before adenoidectomy. He was born in Guatemala, was adopted just after his birth, and had been living in France since that age. Clinical examination was normal. His hemogram showed: erythrocytes: 8,800,000/mm3; hemoglobin: 20.1 g/dl; hematocrit: 66.8%; reticulocytes: 262,000/mm3; platelets: 200,000/mm3; leukocytes: 6,800/mm3. The patient had been given iron salts for the past 3 months without an earlier hemogram. Total red cell mass was 1200 ml (N: 600). The myelogram was normal as was the leukocyte alkaline phosphatases, serum lysozyme and vitamin B12. Blood ferritin was low (3.5 ng/ml). In vitro cultures of erythroid precursors were normal, as was the karyotype of myeloid cells. Blood erythropoietin concentration was 20-293 mU/ml (N:4-14). All the causes of secondary polycythemia were eliminated by appropriate investigations. The patient was treated by phlebotomy in aliquots of 25 ml/kg, twice a month, for 10 months, and was given iron therapy. At the end of treatment, his hemoglobin was 14 g/dl and his hematocrit was 45%. Both progressively increased again one year later, requiring new phlebotomies. The patient was followed for 4 years but no cause for this erythrocytosis was found; it was probably congenital in origin. CONCLUSION: This case of pure erythrocytosis was associated with elevated erythropoietin production. Whether this high secretion is related to receptor dysfunction remains to be determined. PMID- 7987447 TI - [Home parenteral nutrition in children: practical modalities]. AB - Today, the duration of parenteral nutrition (PN) is unlimited. PN is used in digestive tract chronic disease (the digestive tract is either unusable or is at rest) or in oncology, hematology and renutrition before transplantation. Thanks to technical advances, PN, although sophisticated, may be applied at home if an active involvement of one parent is obtained. Home PN is indicated when it is planned for more than 3 months. The indications as a function of the disease, socio-cultural background and the distance to the PN centre are reviewed. The technical modalities such as vascular access, the choice of a catheter, the nutriments to be perfused, the parents' training and the logistic support are studied. Complications of home PN are identical to those of prolonged PN; infections is the most frequent. Results of PN as well as the quality of life of the children are briefly reported. PMID- 7987448 TI - [Antigliadin, antireticulin, antiendomysium antibodies: value in the diagnosis and follow-up of celiac disease in children]. AB - In recent years, the clinical spectrum of coeliac disease has changed and forms with mild aspecific symptoms are today frequent. Therefore many infants are submitted to jejunal biopsy in order to exclude coeliac disease or to allow an early diagnosis. This has led to a search for a simple and reliable diagnostic test of coeliac disease in order to limit the use of jejunal biopsy. Recent data suggest that the study of serum antigliadin, antireticulin and antiendomysium antibodies may possibly play the role. In this paper the working group on coeliac disease of the Groupe Francophone de Gastroenterologie et Nutrition Pediatriques expresses its view on the place of the dosages of these antibodies in the diagnosis and follow up procedures of coeliac disease in infants and children. At the present time, although it allows a simplification of the procedures, these dosages are presently not sufficiently reliable to serve as a substitute of jejunal biopsy. PMID- 7987449 TI - [Current aspects of cystic lymphangioma in the neck]. AB - Cystic hygroma of the neck (CHN) is the result of a defect in the embryonary development of the lymphatic system. In many cases foetal ultrasound allows an early diagnosis before birth, the prognosis being very different according to the gestational age at the time of detection. When discovered before 30 weeks of gestation it is almost always associated with chromosomal abnormality and/or polymalformation leading to spontaneous or therapeutic abortion. On the contrary when appearing after the 30th week of gestation, CHN is usually an isolated malformation as when discovered during infancy or childhood. Approximately 2/3 of these "late" CHN are present at birth; 90% are discovered before 2 years of age. A spontaneous regression occurs in about 15% of the cases. In 70% of cases the CHN is simple without extension to the oropharynx or mediastinum and its complete surgical resection is usually easy. Extension to the oropharynx is present in about 20% of the cases; there is a risk of neonatal respiratory distress and the treatment is difficult. Extension to the mediastinum is found in about 10% of the cases; respiratory distress is rare and a large surgical resection is necessary. Surgery is the primary treatment of CHN after a careful evaluation of the extension of the tumor by ultrasound, scanography or nuclear magnetic resonance, and oropharyngeal endoscopy. It allows a "macroscopically complete" resection in about 80% of the cases, but a recurrence is observed in approximately one every five cases. Following partial resection or important recurrence, treatment includes according to the cases; new attempt of surgical resection, sclerosing therapy, and laser therapy for the oropharyngeal forms. PMID- 7987451 TI - [Evaluation of sport injuries in children and adolescents]. AB - During 1992, 541 sport injuries (6.3% of the 8641 surgical emergencies) were recorded at Lenval's hospital pediatric emergency ward in Nice. There were a majority of boys (62%), and the mean age was 11.2 years. Thirty one sports were represented, mainly soccer (18.5%), bicycle (12.2%), basketball (9.4%), gymnastics (9.4%), ski (9.2%) and equitation (7.8%). Injuries occurred during competition in 12.7% of the cases, school practice in 36.3%, and free practice in 51%. Lesions concerned head and face in 15.5% of cases, the trunk in 9.2%, and limbs in 75.3% with a majority of twists and benign contusions. The hospitalisation's rate was 14.4%, and a surgical intervention with anesthesia was performed in 7.6% of cases to treat one shoulder dislocation and 42 limb fractures. Thirty percent of children were confirmed sportsmen/women, 40% of them were involved in competitive sports, the most frequently concerned sports being soccer (24.6%), basketball (18%), fighting sports (11.4%; 7.2% = judo), gymnastic (10.1%), tennis (7.9%) and equitation (6.7%). From this study most sports injuries in children appears benign even if some fractures led to hospitalisation and orthopedic surgery; this is possibly related to the quality of education and coaching, particularly during physical training at school. PMID- 7987450 TI - [Paracetamol and other antipyretic analgesics: optimal doses in pediatrics]. AB - Acetaminophen is a safe antipyretic therapy prescribed in children. The dosage usually applied in France ranges from 20 to 30 mg/kg/d, which is low and probably with little efficiency in many cases. From the data of the literature the optimal dosage seems to be 65 mg/kg/d using a 25 mg/kg loading dose, followed by a 12.5 mg/kg every 6 hours maintenance dose. The analgesic effect of a 15 mg/kg oral dose has been also demonstrated. Aspirin is equally effective, especially for rheumatic disorders, but its use is limited by adverse reactions. The other nonsteroidal anti-inflammatory drugs have a limited interest. PMID- 7987452 TI - [Radiological case of the month. Giant lobar emphysema]. PMID- 7987453 TI - [Should vitamin D be prescribed in pregnancy?]. PMID- 7987454 TI - [Value of ECG in the examination of syncope]. PMID- 7987455 TI - [Hepatitis A and immune thrombocytopenic purpura]. PMID- 7987456 TI - [Severe poisoning by Lepiota jossrandii]. PMID- 7987458 TI - [Role of hereditary metabolic diseases in pediatric pathology in 1994]. PMID- 7987457 TI - [Resistant pneumococcal meningitis revealing sickle cell anemia]. PMID- 7987459 TI - [The ups and downs of Williams-Beuren syndrome]. PMID- 7987460 TI - [Respiratory outcome in premature infants]. PMID- 7987461 TI - [Gastroesophageal reflux in infants: ultrasonographic reading of pHmetry]. AB - BACKGROUND: pH monitoring of the distal esophagus has proved both sensitive and specific in the detection of reflux but has several limitations due to changes over time in esophageal pH and possibility of alkaline reflux. Simultaneous ultrasonographic monitoring can be helpful when interpreting the results. POPULATION AND METHODS: One thousand infants (80% under 1 year of age) were examined: 500 suffered from vomiting (310 patients), life-threatening events (65 patients) or repeated respiratory diseases (125 patients). Five hundred infants were controls (320 asymptomatic and 180 sibs of patients with SIDS). pHmonitoring and ultrasonography were performed before and after ingestion of milk by vomiting patients and after administration of orange juice in the other symptomatic patients. Control patients were given milk when asymptomatic or orange juice when they belonged to a SIDS sibship. RESULTS: Ultrasonography permitted to interpret the different phases of the pH curves according to the age of patients, the meals and their nature, the events associated with temporary increase in abdominal pressure, the gravity. pH monitoring was able to recognize 1589 acid reflux but failed to recognize 2091 reflux episodes. CONCLUSIONS: While pHmonitoring is helpful to demonstrate a relationship between the reflux and such events as apnea, bradycardia, cough, ultrasonography defines a risk based on specificity of reflux and laryngeal or esophageal dysfunction. PMID- 7987462 TI - [Biliary atresia in French Polynesia. Retrospective study of 10 years]. AB - BACKGROUND: French Polynesia includes several ethnic groups; thus, it is well suited for evaluation of racial incidence of extrahepatic biliary atresia (BA). On the other hand, its geographic localization, far from specialized centers, does not facilitate early referral, indispensable for effective surgery. POPULATION AND METHODS: The files of 17 infants with BA, born in French Polynesia between 1 December 1981 and 1 December 1991, were retrospectively studied. During this period, there were 53,111 live births. RESULTS: The incidence of BA was 1/3,124. There were eight boys and nine girls; all belonged to the Maohi ethnic group (67% of the total population). They were admitted at the mean age of 71 +/- 33 days (range: 15-120 days); 15 of them were transferred to France at a mean age of 80 +/- 38 days (range: 35-150 days) and were operated on at 99 +/- 43 days (range: 48-195 days). The Kasai procedure was effective in four patients, with a follow-up ranging from 7 to 10 years. Among the 11 other patients, two underwent liver transplantation, four are waiting for transplantation and four have died. CONCLUSIONS: The influence of race on the incidence of BA has not been statistically established here even though this incidence appears high in French Polynesia and similar to Chinese babies in Hawaii. Local geographic conditions explain late admission in pediatric Units whereas possibilities for early surgery are improving. PMID- 7987463 TI - [Pneumomediastinum in a young girl with anorexia nervosa]. AB - BACKGROUND: Pneumomediastinum is a rare complication of anorexia nervosa. It may occur in patients with severe weight loss and a history of induced vomiting. CASE REPORT: A 14 year-old girl was admitted suffering from severe anorexia nervosa. Shortly after admission, she complained of anterior thoracic pain. Examination showed subcutaneous emphysema of the supraclavicular fossae and the base of the neck. Thoracic X-ray showed pneumomediastinum without pneumothorax. At the time, the patient admitted to a history of surreptitious chronic induced vomiting. Gastrografin esophagography ruled out an oesophageal tear. The pneumomediastinum gradually disappeared over a period of several days with simple clinical and radiological monitoring. CONCLUSIONS: This case, along with seven others reported in the literature, confirms that pneumomediastinum in anorexia nervosa is usually not accompanied by pneumothorax. An oesophageal perforation must always be ruled out. Spontaneous pneumomediastinum invariably has a favorable outcome. PMID- 7987464 TI - [Periostal effusion in hypernatremic dehydration with disseminated intravascular coagulation]. AB - BACKGROUND: Several cases of hypernatremic dehydration complicated by consumption coagulopathy and peripheral gangrene have been reported. CASE REPORT: A 4.5 month old boy was admitted suffering from acute gastroenteritis with cyanotic edema of the distal part of the left leg and foot. His serum sodium was 160 mEq/l, potassium 5.8 mEq/l and urea 27.6 mMol/l. His prothrombin level was 44%, fibrinogen 0.65 g/l and the number of platelets was 20,000/mm3. Blood cultures were negative. Ultrasonography showed a subperiostal effusion in the posterolateral part of the left tibia with edema of the adjacent soft tissues. Culture of the fluid was negative. The patient was rehydrated. Several phlyctenes appeared on the left foot; cultures of the exudate remained sterile. His condition gradually normalized within two weeks and ultrasonography performed at the 15th day was normal. CONCLUSION: The subperiostal effusion seen in our patient could have been due to microthrombosis of the metaphyseal vessels, following severe dehydration. PMID- 7987465 TI - [Disorder of gender identity in a child with asymmetric gonadal dysgenesis with complex karyotype abnormality]. AB - BACKGROUND: Gender identity is influenced by genetic and hormonal factors and also by the sex of rearing. CASE REPORT: A child was born with ambiguous genitalia. Male sex assignment was made. Hypospadias and left inguinal hernia were present. The hernial sac contained an ovarian tissue. Plasma testosterone, 17-OH progesterone, cortisone levels were normal as were basal FSH and LH levels. There was a vagina but no uterus. The karyotype showed 45X/46XY mosaicism. The testis in the right scrotum was removed and vulvoplasty was performed at the age of 10 months; the patient was than raised as a female. Several courses of reconstructive genital surgery were necessary between 1 and 8 years of age. The girl suffered from trichotillomania and sleep disorders from the age of 4 years and learning difficulties and social phobia from the age of 8. When 11.5 years old, she had clinical features of Turner's syndrome, was depressive but appeared to prefer male playmates. CONCLUSION: Two mechanisms may explain alterations in gender identity in this patient with asymmetric gonadal dysgenesis; 1) early and prolonged androgen exposure as seen in patients with congenital adrenal hyperplasia; 2) insufficient counselling with parents regarding questions of gender identity. PMID- 7987466 TI - [Wolman disease]. AB - BACKGROUND: Wolman disease is a severe disease associated with hepatosplenomegaly and adrenal calcifications; it is nearly always fatal in the first year of life. CASE REPORT: A boy was born to consanguineous parents. His weight was 3,500 g, height 53 cm. Hepatomegaly was observed at the age of 26 days; he also had vomiting and watery stools with failure to thrive. Diagnosis of Wolman disease was suspected due to family history. Two sisters had died at the age of 3 months without precise diagnosis; both had abdominal distension, hepatosplenomegaly, anemia and inanition; CT scan showed calcifications of adrenal glands in one of them that had been attributed to adrenal hemorrhage. Investigations in our patient showed no adrenal calcification, hepatomegaly without splenomegaly, anemia (Hb: 8 g/100 ml). Liver biopsy showed enlarged and vacuolated parenchymal and Kupffer cells but the marrow did not contain foam cells. Acid lipase deficiency was demonstrated in cultured skin fibroblasts, permitting prenatal diagnosis in a further sib. CONCLUSION: This case of Wolman disease was the first seen in Tunisia; it was inherited as an autosomal recessive disorder; this patient, as two of his sisters, died during the first 6 months of life. PMID- 7987467 TI - [Protocol of metabolic investigations in hereditary metabolic diseases]. AB - The authors describe a laboratory investigations protocol to be used by pediatricians facing conditions suggestive of inherited metabolic disorders. This protocol includes: 1) an emergency screening to be systematically performed during the acute clinical phase; 2) samplings to be kept frozen for possible secondary specific investigations according to the results of the emergency screening. In addition a perimortem protocol is also presented, to be applied in every lethal situations in which an inherited metabolic disorder is suspected. The equipment required in order for the clinician to properly perform the different investigations is also described. PMID- 7987468 TI - [Sexually transmitted diseases in women, mothers, under-age females. 7th Consensus Conference on Antiinfectious therapy. Paris, 3 November 1993]. AB - This paper is a report of a consensus conference held by the "Societe de pathologie infectieuse de langue francaise" on diagnosis and treatment of sexually transmitted diseases in females (HIV and hepatitis B being excluded). Three subjects are concerned. 1) Diagnosis and medical treatment of salpingitis, with particular attention to salpingitis in adolescent girls, the two most common infections being Chlamydia trachomatis and Neisseria gonorrhoeae. 2) Diagnosis and treatment of sexually transmitted diseases in girls younger than 15, with the underlying question of possible sexual abuse. 3) The neonatal consequences of maternal sexually transmitted diseases and their treatment (Neisseria gonorrhoeae, Treponema Pallidum, Mycoplasma, Chlamydia trachomatis, Herpes, Cytomegalovirus, Papillomavirus). PMID- 7987469 TI - [Rubinstein-Taybi syndrome]. AB - The Rubinstein-Taybi syndrome (RTS) is a well-defined complex of congenital malformations characterized by mental and growth retardation, broad thumbs, broad big toes, and typical face. A locus for a gene involved in the origin of RTS has been determined on chromosome 16 (16p13.3). RTS is caused by submicroscopic interstitial deletions within 16p13.3 in approximatively 25% of patients, using fluorescence in situ hybridization with specific probes. PMID- 7987470 TI - [Intraosseous vascular access, a technic previously underestimated in France]. AB - Intraosseous vascular access is a simple and very efficient technique for fluid and drug administration in any pediatric emergencies where the intravenous route is impossible or inadequate. Yet it remains unrecognized in France. Its pharmacokinetics is close to that of peripheral intravenous route, but it allows much greater infusion flow rates. In pediatric resuscitation it must be considered as the number one technique of intravascular access in infants, and rapidly as the first alternative after failure of attempt of intravenous route in children under 6. Provided that the technique is performed with careful asepsis, the risk of infectious complications is very low. However the intraosseous route must remain a transitory vascular access, and has to be stopped as soon as possible, its use never exceeding 24 hours. PMID- 7987471 TI - [The letter from the Societe Francophone de Recherche en Pediatrie]. PMID- 7987472 TI - [Radiological case of the month. A case of craniolacunia]. PMID- 7987473 TI - [Incidence of intolerance to cow's milk protein following administration of a prescription drug]. PMID- 7987474 TI - [Neonatal salmonella infection]. PMID- 7987475 TI - [Mycotic aneurysm of the iliac artery]. PMID- 7987476 TI - Interaction of Cibacron blue with polymers: implications for polymer-shielded dye affinity chromatography of phosphofructokinase from baker's yeast. AB - Interactions between Cibacron Blue F3GA and water-soluble non-ionic polymers were investigated by monitoring the spectral shift that accompanies the binding phenomena. Polyvinylpyrrolidone (PVP) and poly(vinyl alcohol) were the only polymers among those tested found to interact effectively with the dye. The difference spectra for the PVP-dye complex was typical of "electrostatic interaction spectra" at low ionic strength and typical of "hydrophobic interaction spectra" in the presence of 1.5 M KCl. The binding constant and the number of binding sites per polymer molecule were calculated using the simplest model of independent binding sites. One dye molecule was bound by a PVP segment with a molecular mass of 1000-1300. Regardless of the size of the polymer molecules, the binding constants were in the micromolar range. Poly(vinyl alcohol) bound less efficiently to Cibacron Blue than PVP. One dye molecule was bound by a polymer segment with a molecular mass of about 10,000. The data on PVP complexing with Cibacron Blue were used to develop the concept of polymer shielded dye-affinity chromatography. This concept was successfully applied to the chromatography of phosphofructokinase (EC 2.7.1.11) from baker's yeast. Specific elution of the bound enzyme from PVP-shielded column resulted in an efficient process with 27-fold purification. PMID- 7987477 TI - Presence of a preferred anion-exchange binding site on cytochrome b5: structural and thermodynamic considerations. AB - A preferred chromatographic contact region for adsorption of recombinant soluble tryptic fragment of rat cytochrome b5 on the hydrophilic anion-exchanger Mono Q has been identified using conservative carboxylate-to-amide mutations of charged residues. Equilibrium adsorption isotherms were measured under conditions of full reversibility by high ionic strength, as confirmed by explicit mass balances performed for each experiment. Although cytochrome b5 displays several clusters of negative charge, mutations in one cluster consistently reduce binding affinity and the stoichiometric displacement parameter Z by much greater factors than do mutations in other areas of the molecule. Adsorption heterogeneity derived by fitting isotherms to the Hill equation is reduced by factors which reduce the overall affinity of adsorption. Van't Hoff analyses gave uniformly positive enthalpies of adsorption, and mutational changes in adsorption enthalpy were relatively independent of the site of mutation. These results suggest that enthalpy does not play a dominant role in either affinity or selectivity of anion exchange adsorption in this system. PMID- 7987478 TI - High-performance anion exchange of small anions with polyethyleneimine-coated porous zirconia. AB - The preparation and chromatographic characterization of an ion-exchange high performance liquid chromatographic support by deposition and crosslinking of polyethyleneimine (PEI) on the surface of porous zirconia is described. Adsorption and evaporation methods were used for coating PEI onto the zirconia particles. These two stationary phases were compared by elemental analysis, ion exchange capacity and by chromatography. High efficiency and good selectivity were observed for inorganic and organic anions. The addition of a strong, hard Lewis base to the mobile phase dramatically improved the peak shape and efficiency of para benzoic acid derivatives. PEI-coated zirconia showed a distinct elution sequence for organic anions when compared to bare zirconia or silica-based phases. The polyamine coated zirconia was stable over a pH range from 2.75 to 9. Flow studies, using nitrite as a probe solute, showed that both coating procedures produced packed columns with good mass-transfer properties. PMID- 7987479 TI - Dependence of the electroosmotic mobility on the applied electric field and its reproducibility in capillary electrophoresis. AB - Experimental results on the electroosmotic mobility in fused-silica capillaries are presented for different applied voltages and solutions of different pH. The electroosmotic mobility is shown to be dependent on the applied voltage and this dependence cannot be attributed to the temperature effects. Results of the electroosmotic mobility measurements are found to be dependent also on the electrophoresis unit they have been performed in. The explanation given and the relevant theory presented are based on the hypothesis that these effects are produced by a radial electric field inevitably existing in any electrophoresis unit. The concept of the limiting electrophoretic mobility, i.e. extrapolated to the zero applied voltage, is introduced in order to characterize the properties of the solution-wall interface. The slope of the electroosmotic mobility dependence on the applied voltage depends on the solution pH and the surroundings of the capillary. Theoretical estimations agree well with both experimentally found limiting mobilities and slopes. Long-term variations of the electroosmotic mobility are supposed to be related with the cation penetration into the capillary wall. PMID- 7987480 TI - High-performance liquid chromatographic analysis of glycoamines in serum. AB - This report describes the development of an HPLC-UV method for studies of glycoamines and glycoamine-like compounds in normal human serum and osteosarcoma patients serum as potential biological markers of cancer. The glycoamines, a newly recognized class of endogenous, low-molecular-mass biopolymers, are conjugates of amino acids and sugar units, containing 5 to 29 amino acid and 1 to 17 sugar units. After ultrafiltration of serum samples, reversed-phase HPLC separation with diode-array detection was used to obtain standard profiles of serum ultrafiltrates below M(r) 10,000 in healthy subjects. These highly reproducible profiles utilized two-dimensional peak identification and were used to develop a statistical profile of the major glycoamine peaks in normal serum. This newly developed analytical method was subsequently used to address a key question: whether or not there is a single tumor-specific glycoamine or a family of tumor-specific glycoamines in cancer patient serum. Preliminary results suggest that this method can separate and detect glycoamines and glycoamine-like compounds in various types of cancer patients serum with a high degree of reproducibility on the basis of comparative two-dimensional identification of natural compounds and a panel of synthetic glycoamine analogs. Moreover, the method is useful for following the relative changes in the amount of a given glycoamine over an extended clinical time course. Initial results suggest that a glycoamine or glycoamine-like compound, GA-4.63, may have clinical utility in human osteosarcoma studies. PMID- 7987481 TI - Determination of pyridinium crosslinks in plasma and serum by high-performance liquid chromatography. AB - A chromatographic method for the determination of pyridinoline (Pyr) and deoxypyridinoline (Dpyr) in serum and plasma is described. The analytical procedure involved plasma or serum purification by ultrafiltration (20,000 relative molecular mass cut-off) under centrifugation at 2500 g for 4 h, as an innovative step. Analysis was done by isocratic high-performance liquid chromatography with fluorescence detection. The linearity of the method was tested from 0.6 to 15 pmol/ml and 0.12 to 3 pmol/ml for Pyr and Dpyr, respectively. The detection limit was 60 fmol/ml for both crosslinks. Except for Dpyr in plasma (coefficient of variation 19.9%), intra-assay variation was always below 10% in serum and plasma. The method has been applied to the quantification of crosslinks in serum and plasma of healthy volunteers and also in mouse and rat plasma. Serum proved to be the most suitable biological fluid for the systemic measurement of these compounds in humans and under the experimental conditions used, contained an average of 3.62 +/- 0.65 and 0.7 +/- 0.18 pmol/ml Pyr and Dpyr, respectively. PMID- 7987482 TI - Rapid determination of glutathione status in fish liver using high-performance liquid chromatography and electrochemical detection. AB - A rapid and sensitive method for the detection of reduced (GSH), oxidised (GSSG) and protein-bound (PSSG) glutathione in fish liver, using reversed-phase HPLC with electrochemical detection has been developed. Separation was carried out isocratically at room temperature using 0.020 M sodium phosphate, pH 2.7 as mobile phase. A series dual-channel electrochemical detector was used for the simultaneous determination of GSH and GSSG. PSSG was determined after reduction by 1,4-dithiothreitol. The detection limits found for a 3:1 signal-to-noise ratio were 16.2 and 8.1 pmol for GSH and GSSG, respectively. The results obtained demonstrate that this method could be useful for measurement of the glutathione redox status in fish liver and are consistent with those reported for other fish. The method has been applied to follow the oxidative stress induced in vivo by copper(II) ions in the gilthead seabream fish (Sparus aurata). At longer times after copper(II) injection, the glutathione redox status of the exposed fish returned to a more reduced state, suggesting the existence of adaptive processes. PMID- 7987483 TI - Biological monitoring of hexamethylene diisocyanate by determination of 1,6 hexamethylene diamine as the trifluoroethyl chloroformate derivative using capillary gas chromatography with thermoionic and selective-ion monitoring. AB - A GC method using a novel derivatization reagent, 2',2',2-trifluoroethyl chloroformate (TFECF), for the derivatization of primary and secondary aliphatic amines with the formation of carbamate esters is presented. The method is based on a derivatization procedure in a two-phase system, where the carbamate ester is formed. The method is applied to the determination of 1,6-hexamethylene diamine (HDA) in aqueous solutions and human urine, using capillary GC. Detection was performed using thermionic specific detection (TSD) and mass spectrometry (MS) selective-ion monitoring (SIM) using electron-impact (EI) and chemical ionization (CI) with ammonia monitoring both positive (CI)+ and negative ions (CI)-. Quantitative measurements were made in the chemical ionization mode monitoring both positive and negative ions. Tetra-deuterium-labelled HDA (TDHDA; H2NC2H2(CH2)4C2H2NH2) was used as the internal standard for the GC-MS analysis. In CI+ the m/z 386 and the m/z 390 ions corresponding to the [M + 18]+ ions (M = molecular ion) of HDA-TFECF and TDHDA-TFECF were measured; in CI- the m/z 267 and the m/z 271 ions corresponding to the [M - 101]- ions. The overall recovery was found to be 97 +/- 5% for a HDA concentration of 1000 micrograms/l in urine. The minimal detectable concentration in urine was found to be less than 20 micrograms/l using GC-TSD and 0.5 micrograms/l using GC-SIM. The overall precision for the work-up procedure and GC analysis was ca. 3% (n = 5) for 1000 micrograms/l HDA-spiked urine, and ca. 4% (n = 5) for 100 micrograms/l. The precision using GC-SIM for urine samples spiked to a concentration of 5 micrograms/l was found to be 6.3% (n = 10). PMID- 7987484 TI - Determination of aflatoxin Q1 in urine by automated immunoaffinity column clean up and liquid chromatography. AB - A liquid chromatographic system with an automated clean-up procedure for aflatoxin Q1 in human urine is described. The samples were cleaned up by using immunoaffinity columns originally designed for aflatoxin M1. The chromatographic system was a C18 column with an acidic mobile phase of acetonitrile-water containing potassium bromide. Fluorescence detection (365/440 nm) of aflatoxin Q1 was enhanced by addition of bromine, using post-column derivatization, which was studied by factorial designs. Average recovery of aflatoxin Q1 in spiked 10-ml urine samples was 88% (R.S.D. = 6.4%) at a level of 50 pg/ml. The determination limit was 49.5 pg/ml urine. PMID- 7987485 TI - Determination of plasma cocaine and ethylcocaine (cocaethylene) in mice using gas chromatography-mass spectrometry and deuterated internal standards. AB - A gas chromatographic-mass spectrometric method is described for the determination of cocaine and ethylcocaine (cocaethylene) from mouse plasma microsamples (50 microliters). [2H3]Cocaine and [2H5]ethylcocaine served as internal standards, analytical separations were performed on a (5% phenyl)methylpolysiloxane capillary column, and detection was by selected-ion monitoring of electron-impact generated fragment ions [M - CO2Ph]. Pilot study plasma concentrations of ethylcocaine following coadministration of cocaine and ethanol were less than 5% of the parent drug. PMID- 7987486 TI - Sensitive capillary gas chromatographic-mass spectrometric method for the therapeutic drug monitoring of valproic acid and seven of its metabolites in human serum. Application of the assay for a group of pediatric epileptics. AB - A sensitive capillary gas chromatographic-mass spectrometric method for the determination of valproic acid and 7 of its metabolites is described. It is based on the selected-ion monitoring of the tert.-butyldimethylsilyl derivatives using N-(tert.-butyldimethylsilyl)-N-methyl-trifluoracetamid (MTBSTFA) as the derivatization reagent. The limits of detection for valproic acid and its metabolites are in the low ng/ml-range, except for the 4-hydroxy metabolite with a limit of detection of 100 ng/ml. The method has been tested against an established GC method for valproic acid. The assay has been used for therapeutic drug monitoring in epileptic pediatric patients. The concentrations of the omega- and omega 1-oxidation metabolites in a group of patients receiving additional antiepileptic drugs were found to be significantly enhanced compared to the levels found in a monotherapy group. PMID- 7987487 TI - Column-switching high-performance liquid chromatographic analysis of BO-2727, a new carbapenem antibiotic, in human plasma and urine by direct injection. AB - A column-switching high-performance liquid chromatographic method has been developed for the simple and sensitive analysis of BO-2727 (I) in human plasma and urine. Plasma samples were diluted with an equal volume of a stabilizer, and the mixture was directly injected onto the HPLC system. The analyte was enriched in a pre-treatment column, while endogenous components were eluted to waste. The analyte was then backflushed onto an analytical column and quantified with ultraviolet detection. Urinary concentrations were determined in a similar way except that the enriched analyte was eluted in the foreflush mode to a cation exchange column used for chromatographic separation. The standard curves for the drug were linear in the range of 0.05-50 micrograms/ml in plasma and 0.5-100 micrograms/ml in urine. The limits of quantification for plasma and urine were found to be 0.5 micrograms/ml and 0.5 micrograms/ml, respectively. This method was used to support Phase I clinical pharmacokinetic studies. PMID- 7987489 TI - Determination of azosemide and its metabolite in plasma, blood, urine and tissue homogenates by high-performance liquid chromatography. AB - High-performance liquid chromatographic methods were developed for the determination of azosemide and its metabolite, M1, in human plasma and urine and rabbit blood and tissue homogenates. The methods involved deproteinization of the biological samples: 2.5 volumes of acetonitrile were used for the determination of azosemide and 1 volume of saturated Ba(OH)2 and ZnSO4 for that of M1. A 50 microliters aliquot of the supernatant was injected onto a C18 reversed-phase column in each instance. The mobile phases employed were 0.03 M phosphoric acid acetonitrile (50:40, v/v) for azosemide and 0.03 M phosphoric acid/0.2 M acetic acid-acetonitrile (83:17, v/v) for M1. The flow-rate was 1.5 ml/min in both instances. The column effluent was monitored by ultraviolet detection at 240 and 236 nm for azosemide and M1, respectively. The retention times for azosemide and M1 were 6.0 and 8.3 min, respectively. The detection limits for both azosemide and M1 in both human plasma and urine were 50 ng/ml. The coefficients of variation of the assay were generally low (below 11.0%) for plasma, urine, blood and tissue homogenates. No interferences from endogenous substances or other diuretics tested were observed. PMID- 7987488 TI - Determination of MDL 74,405, a synthetic analogue of alpha-tocopherol, in dog plasma and heart tissue by high-performance liquid chromatography with electrochemical detection. AB - A high-performance liquid chromatographic (HPLC) procedure with electrochemical detection was developed to analyze MDL 74,405 (I), the (-)-(S)-enantiomer of an alpha-tocopherol analogue, in dog plasma and heart tissue after infusion (0.3 mg/kg/h). The sample preparation involved the addition of an internal standard to either the dog plasma and heart tissue prior to protein precipitation. After centrifugation, the resulting supernatant was directly analyzed by HPLC with a Zorbax Rx C8 column and a mobile phase of acetonitrile-0.04 M potassium phosphate, pH 7.0 (70:30, v/v). The concentration of I found was ca. 100 ng/ml in plasma and ca. 3 micrograms/g in heart tissue. A chiral separation with an Ultron ES-OVM column and a mobile phase of methanol-0.025 M potassium phosphate, pH 6.5 (17:83, v/v) was also used to investigate the enantiomeric conversion of I. Preliminary results of a probe study indicated that I is not inverted to the (+) (R)-enantiomer in vivo. PMID- 7987490 TI - Simultaneous determination of plasma haloperidol and its metabolite reduced haloperidol by liquid chromatography with electrochemical detection. Plasma levels in schizophrenic patients treated with oral or intramuscular depot haloperidol. AB - A simple and highly sensitive liquid chromatographic method with electrochemical detection for the simultaneous determination of haloperidol and its metabolite reduced haloperidol in human plasma has been developed. The sample preparation for the analysis involves a simple one-step extraction procedure with 10% methylene chloride in pentane. The compounds were separated on a cyano column maintained at a temperature of 40 degrees C and were detected electrochemically by a flow-through analytical cell kept at +0.95 V. The standard curve is linear over the range of 0.1 to 15 ng/ml and the lower limit of quantitation is 0.1 ng/ml for haloperidol and 0.25 ng/ml for reduced haloperidol which is equivalent to approximately 40 pg on column when 1 ml of plasma was used for the analysis. The lower limit of quantitation for reduced haloperidol can be extended to 0.1 ng/ml if 2 ml of plasma is used in the analysis. The coefficient of variation of the determination of plasma levels by this method over the standard curve concentration range was less than 10%. Commonly co-administered drugs and other neuroleptics used in conjunction with haloperidol did not interfere in the determination of either haloperidol or reduced haloperidol. This method has been successfully used for the determination of haloperidol and reduced haloperidol in plasma and their levels in patients treated with various doses oral haloperidol or intramuscular haloperidol decanoate are reported. PMID- 7987491 TI - High-performance liquid chromatographic method for the determination of cefpodoxime levels in plasma and sinus mucosa. AB - A selective HPLC method is described for the determination of cefpodoxime levels in plasma and sinus mucosa. Sample preparation included solid-phase extraction with a C8 cartridge. Cefpodoxime and cefaclor (internal standard) were eluted with methanol and analyzed on an optimised system consisting of a C18 stationary phase and a ternary mobile phase (0.05 M acetate buffer pH 3.8-methanol acetonitrile, 87:103, v/v) monitored at 235 nm. Linearity and both between- and within-day reproducibility were assessed for plasma and sinus mucosa samples. Inter-assay coefficients of variation were lower than 13.6% (n = 10) for plasma (0.2 micrograms/ml) and lower than 12.4% (n = 5) for sinus mucosa (0.25 micrograms/g). The quantification limit was 0.05 micrograms/ml for plasma and 0.13 micrograms/g for tissue. The method was used to study the diffusion of cefpodoxime in sinus mucosa. PMID- 7987492 TI - Quantification of 3'-amino-3'-deoxythymidine, a toxic catabolite of 3'-azido-3' deoxythymidine (zidovudine) in human plasma by high-performance liquid chromatography using precolumn derivatization with fluorescamine and fluorescence detection. AB - A specific and sensitive high-performance liquid chromatographic (HPLC) assay with precolumn derivatization and fluorescence detection was developed for the determination of 3'-amino-3'-deoxythymidine (AMT), a recently characterized toxic catabolite of 3'-azido-3'-deoxythymidine (zidovudine, AZT). After extraction with tert.-butyl methyl ether-1-butanol (6:4, v/v) and back-extraction into basified aqueous phase, the solution was neutralized with phosphate buffer and the compound derivatized with fluorescamine. Fluorescamine-labeled AMT was chromatographed on a reversed-phase C18 column using a mixture of phosphate buffer-methanol-acetonitrile (47:48:5, v/v/v) as mobile phase and fluorescence detection (excitation wavelength 265 nm, emission wavelength 475 nm). The limit of quantification was 3 ng/ml using a 200-microliters plasma sample. The recovery of the extraction procedure averaged at 94.4% in the range of 3-200 ng/ml. The HPLC analysis time required per sample was 16 min. Replicate analyses of quality control samples (5-80 ng/ml) gave satisfactory intra- and inter-assay precision (coefficient of variation varied from 1.9 to 6.7%) and accuracy. PMID- 7987493 TI - Determination of the concentrations of 5-fluorouracil and its metabolites in rabbit plasma and tissues by high-performance liquid chromatography. AB - The concentrations of 5-fluorouracil, 5-fluoro-5,6-dihydrouracil, 5-fluorouridine and 5-fluoro-2'-deoxyuridine in plasma, liver, kidney, lung and heart of rabbits were determined by high-performance liquid chromatography (HPLC) after drug administration by two different routes. HPLC was carried out by using a Spherisorb 5 ODS 2 column and 0.05 M phosphate buffer as the mobile phase with UV detection at 200 nm. The pH of the mobile phase, organic modifier content and column temperature were found to have a profound influence on the results, hence it was necessary to optimize a procedure for each matrix. A comparison of the efficiency of intravenous and peritoneal administration revealed that the latter provides higher drug concentrations in the liver and minimal contents in plasma and all other tissues studied. PMID- 7987494 TI - Simultaneous determination of a new anthracycline, DA-125, and its metabolites M1, M2, M3 and M4 in plasma and urine by high-performance liquid chromatography. AB - A high-performance liquid chromatographic method was developed for the simultaneous determination of a new anthracycline, DA-125 (I), and its metabolites (M1, M2, M3, and M4) in rat plasma and urine using fluorescein as an internal standard. Compound I, a prodrug of M1, is a beta-alanine derivative of M1, and only M1 shows antineoplastic activity. The method involved extraction or deproteinization followed by injection of 80-100 microliters of the aqueous layer or supernatant onto a C18 reversed-phase column. The mobile phases were 1% acetic acid-isopropyl alcohol-methanol (70:20:10, v/v) or 5 mM of ion-pairing chromatography reagent (IPC B8)-isopropyl alcohol-methanol (70:20:10, v/v) for the extraction or deproteinization methods, respectively. The flow-rate was 1.5 ml/min for both methods. The column effluent was monitored by a fluorescence detector with excitation wavelength of 488 nm and emission wavelength of 556 nm. The detection limits for M1, M2, M3, and M4 in rat plasma and urine were 50 ng/ml for all compounds using the extraction method, and 100, 50, 50, 50, and 50 ng/ml for I, M1, M2, M3 and M4 in rat plasma respectively, using the deproteinization method. No interferences from endogenous substances, adriamycin or daunorubicin were found. PMID- 7987495 TI - High-performance liquid chromatographic assay of the magnetic resonance imaging contrast agent gadobenate in plasma, urine and bile. AB - Gadobenate dimeglumine (Gd-BOPTA-Dimeg) is currently under evaluation as an intravascular paramagnetic contrast agent for magnetic resonance imaging. The anion Gd-BOPTA2- is the moiety of Gd-BOPTA-Dimeg responsible for contrast enhancement. An HPLC method for assaying gadobenate (Gd-BOPTA2-) in plasma, urine and bile samples is described. The analysis is based on the reversed-phase chromatographic separation of the ion pair Gd-BOPTA(2-)-tetrabutylammonium from the endogenous components of biological fluids and its detection by UV absorption at 210 nm. The mean accuracy and precision of the method were in the range -3.4 to +5.0% and 0.2-3.5%, respectively. The method detection limits for Gd-BOPTA2- in plasma (0.8 ml), urine (0.2 ml) and bile (1.0 ml) were 1.1, 7.6 and 1.7 microM (corresponding to 0.73, 5.1 and 1.1 micrograms/ml), respectively. PMID- 7987496 TI - Immobilization of heparin on polyacrylamide derivatives. AB - Heparin was coupled via its carboxyl group with a polyacrylamide derivative containing covalently bound amino groups using the carbodiimide reaction. Heparin immobilized in this way proved to be useful as an affinity carrier for the isolation of antithrombin III and heparin-binding proteins from boar seminal plasma. PMID- 7987497 TI - Modification of glass channel walls for separation of biological particles by gravitational field-flow fractionation. AB - In the gravitational field-flow fractionation of complex samples, various interaction and adsorption phenomena can occur in separation channels that influence fractionation and complicate the explanation of resulting fractograms. To overcome these problems, the glass surface was modified to create charge-free, non-adsorbing hydrophilic media for the mild treatment of hydrophilic biological particles. The modification was carried out in two steps: (1) by a simple lacquering of the glass surface with polystyrene diluted in toluene and (2) subsequent adsorption of a detergent layer on polystyrene. Essential suppression of ionic interactions between soluble low-molecular-mass compounds and the channel wall and decreased adsorption effects were demonstrated in separations of blood samples by gravitational field-flow fractionation. PMID- 7987498 TI - Use of metal-chelate affinity chromatography and hydrophobic interaction chromatography for purification of placental protein 12. AB - Placental protein 12 was isolated from amniotic fluid. Albumin was removed by means of ion-exchange chromatography on DEAE-Sepharose and chromatography on Blue Sepharose. Complete purification was obtained by metal-chelate affinity chromatography and hydrophobic interaction chromatography under mild conditions for desorption. Using this procedure large quantities of a highly purified preparation can be obtained in one run. PMID- 7987499 TI - Determination of non-protein-bound iron in human synovial fluid by high performance liquid chromatography with electrochemical detection. AB - Non-protein-bound iron in human synovial fluid was determined using high performance liquid chromatography with electrochemical detection. The procedure was based on the separation of the iron-diethylenetriaminepentaacetic acid (DTPA) complex formed directly on a chromatographic column containing an anion-exchange resin followed by electrochemical detection. The method enabled more than 0.1 microM Fe(III) to be determined with an injection volume of 10 microliters. A mixture of synovial fluid, 20 microM DTPA and acetate buffer was incubated in the presence and absence of superoxide (O2-) generated by a xanthine-xanthine oxidase system and was ultrafiltered through a 30,000 molecular mass cut-off filter. No iron was detected in the ultrafiltrate at physiological pH. However, the presence of iron was observed in the ultrafiltrate at low pH, and O2- facilitated the release of iron into the synovial fluid. This result suggested that in an inflamed joint with generated O2- and decreased pH, iron may be released into the synovial fluid. PMID- 7987500 TI - Gas chromatographic-mass spectrometric determination of ibuprofen enantiomers in human plasma using R(-)-2,2,2-trifluoro-1-(9-anthryl)ethanol as derivatizing reagent. AB - A relatively rapid, inexpensive, sensitive and stereospecific gas chromatographic mass spectrometric method was developed for the quantification of S(+) and R(-) ibuprofen in human plasma. This method uses a commercially available internal standard and has no interference from endogenous substances nor metabolites. The method involves derivatization of ibuprofen enantiomers with optically active R( )-2,2,2-trifluoro-1-(9-anthryl)ethanol using oxalyl chloride as the coupling reagent. The subsequently formed diastereoisomers are separated by gas chromatography and analysed by mass spectrometry using selected-ion monitoring. The assay is successfully applied to a pharmacokinetic study. The simplicity, sensitivity and precision of the method make it convenient for the quantification of ibuprofen enantiomers in biological samples. PMID- 7987501 TI - Determination of indomethacin and mefenamic acid in plasma by high-performance liquid chromatography. AB - Indomethacin and mefenamic acid are widely used clinically as non-steroidal anti inflammatory agents. Both drugs have also been found effective to produce closure of patent ductus arteriosus in premature neonates. A simple, rapid, sensitive and reliable HPLC method is described for the determination of indomethacin and mefenamic acid in human plasma. As these drugs are not applied together, the compounds are alternately used as analyte and internal standard. Plasma was deproteinized with acetonitrile, the supernatant fraction was evaporated to dryness and the resulting residue was reconstituted in the mobile phase and injected into the HPLC system. The chromatographic separation was performed on a C18 column (250 x 4.6 mm I.D.) using 10 mM phosphoric acid-acetonitrile (40:60, v/v) as the mobile phase and both drugs were detected at 280 nm. The calibration graphs were linear with a correlation coefficient (r) of 0.999 or better from 0.1 to 10 micrograms/ml and the detection limits were 0.06 micrograms/ml for indomethacin and 0.08 micrograms/ml for mefenamic acid, for 50-microliters plasma samples. The method was not interfered with by other plasma components and has been found particularly useful for paediatric use. The within-day precision and accuracy of the method were evaluated for three concentrations in spiked plasma samples. The coefficients of variation were less than 5% and the accuracy was nearly 100% for both drugs. PMID- 7987502 TI - Quantitation of the dexrazoxane hydrolysis product ADR-925 by fluorescence detection of its terbium(III) complex after high-performance liquid chromatographic separation. AB - An HPLC fluorescence detection method was developed to quantitate the complexing agent ADR-925 (II). Compound II is the metal-ion-binding rings-opened hydrolysis product of the doxorubicin cardioprotective drug dexrazoxane (I). II formed a strong complex with the fluorescent metal-ion terbium(III) and this complex could be chromatographed by HPLC and detected by its fluorescence, with excitation and emission wavelengths of 200 and 544 nm, respectively. The terbium(III)-II complex was separated isocratically on a C18 reversed-phase column with an eluent consisting of 50% methanol and 50% 4 mM aqueous solution of the ion-pairing reagent 1-heptanesulfonate. The lower limit of detection of II, quantitated as its fluorescent terbium(III) complex, was estimated to be 25 pmol, which was some twenty times lower than with UV-Vis absorbance detection. The fluorescent detection method was used to follow the hydrolysis of I to II in buffer and in blood plasma. PMID- 7987503 TI - Simple and sensitive assay of zonisamide in human serum by high-performance liquid chromatography using a solid-phase extraction technique. AB - A rapid and sensitive method for the assay of zonisamide in serum was developed using a solid-phase extraction technique followed by high-performance liquid chromatography. A 20-microliter volume of human serum was first purified with a Bond-Elut cartridge column. Then, the methanol eluate was injected onto a reversed-phase HPLC column with a UV detector. The mobile phase was acetonitrile methanol-distilled water (17:20:63, v/v) and the detection wavelength was 246 nm. The detection limit was 0.1 micrograms/ml in serum. The coefficients of variation were 4.2-5.6% and 5.1-9.1% for the within-day and between-day assays, respectively. This method can be used for clinical pharmacokinetic studies of zonisamide in serum even in infant patients with epilepsy. PMID- 7987504 TI - High-performance liquid chromatographic assay of cefazolin in rat tissues. AB - A rapid, sensitive and reproducible high-performance liquid chromatographic (HPLC) assay for cefazolin in rat tissues was developed. Tissue samples were homogenized in distilled water, acidified with 8.5% phosphoric acid, and centrifuged. Cefazolin was isolated from the supernatant by solid-phase extraction on C18 cartridges. The eluate containing cefazolin and internal standard, cephalexin, was injected onto a reversed-phase C18 column and eluted with a mobile phase of 23% methanol in 0.02 M sodium phosphate monobasic (pH 5.0) and detected with UV absorbance at 270 nm. Recoveries of cefazolin were 33.7 +/- 2.5%, 45.4 +/- 2.1%, and 42.9 +/- 1.0% from liver, spleen and lung, respectively. The calibration curves for cefazolin were established at 0.5-1500 micrograms/g in spleen, 0.1-250 micrograms/g in liver and 0.1-75 micrograms/g in lung. The assay was reproducible with within-day and between-day variations of 1-2 and 1-4%, respectively. Application of the assay for tissue distribution of cefazolin in liposomal targeting study was demonstrated. PMID- 7987505 TI - High-performance liquid chromatography with UV detection and diode-array UV confirmation of isonicotinic acid hydrazide in cattle milk. AB - A method for the determination of isonicotinic acid hydrazide (isoniazid) in milk was developed. Milk was deproteinized with trichloroacetic acid. Isoniazid was condensed with cinnamaldehyde and assayed on a reversed-phase HPLC system, with good sensitivity and accuracy (10 micrograms/l) with UV detection at 330 nm. Use of solid-phase extraction with a C18 cartridge allows the detection limit to be lowered to 0.1 microgram/l with UV detection and confirmation of isoniazid hydrazone from the diode-array UV spectrum. PMID- 7987506 TI - Predicting work status for patients in an occupational medicine setting who report back pain. PMID- 7987507 TI - The four A's of decreasing the toll of childhood iron poisoning deaths. PMID- 7987508 TI - When 1 + 2 does not equal 3 for hard-working rural physicians. PMID- 7987509 TI - Matching physician practice style to patient informational issues and decision making preferences. An approach to patient autonomy and medical paternalism issues in clinical practice. AB - The movement away from traditional medical paternalism toward increased patient autonomy presents difficult practical and ethical problems for the physician treating the wide variety of patients seen in clinical practice. A review of the literature supports the concept of matching the physician's practice style with both patient informational issues and the patient's desire to actively participate in medical decision making. Studies also support that this matching principle not only improves physician-patient relationships but is ethically defensible and results in improved clinical outcomes. This article presents such a patient-physician match model as an aid to the practicing clinician. PMID- 7987510 TI - Oral sumatriptan in the treatment of recurrent headache. AB - BACKGROUND: Sumatriptan is effective for the treatment of acute migraine. However, headache may recur in about 30% of patients within 24 hours of successful treatment. OBJECTIVE: To evaluate the efficacy of oral sumatriptan, 100 mg, in the treatment of headache recurring within 24 hours of achieving headache resolution with subcutaneous sumatriptan, 6 mg. STUDY DESIGN: Subcutaneous sumatriptan was administered for up to 12 migraine attacks in a randomized, double-blind, parallel-group study. Patients whose headache was completely resolved 90 minutes after subcutaneous dosing received either oral sumatriptan or placebo at the onset of recurrent headache. Patients whose headache was not completely resolved were offered rescue medication, including sumatriptan. Patients rated headache severity for 24 hours. SETTING: Fifteen US outpatient clinics. MAIN OUTCOME MEASURE: Percentage of patients with relief of recurrent headache and adverse events. RESULTS: Approximately 90% of patients achieved relief of headache (severe or moderate headache reduced to mild or no headache) by 90 minutes after unblinded subcutaneous administration of sumatriptan. Efficacy rates were at least 80% regardless of whether the headache fulfilled the International Headache Society criteria for migraine. About 64% of patients achieved complete relief. Oral sumatriptan, 100 mg, relieved moderate or severe recurrent headache within 4 hours in up to 81% of patients. Oral sumatriptan administered as rescue medication to patients not headache-free did not relieve persistent headache. The incidence, pattern, and severity of adverse events after combined subcutaneous and oral administration of sumatriptan were similar to those after subcutaneous administration alone. CONCLUSIONS: Oral sumatriptan was consistently effective in the treatment of headache recurrence. PMID- 7987511 TI - Physical symptoms in primary care. Predictors of psychiatric disorders and functional impairment. AB - OBJECTIVE: To examine how the type and number of physical symptoms reported by primary care patients are related to psychiatric disorders and functional impairment. DESIGN: Outpatient mental health survey. SETTING: Four primary care clinics. PATIENTS: One thousand adult clinic patients, of whom 631 were selected randomly or consecutively and 369 by convenience. MAIN OUTCOME MEASURES: Psychiatric disorders as determined by the Primary Care Evaluation of Mental Disorders procedure; the presence or absence of 15 common physical symptoms and whether symptoms were somatoform (ie, lacked an adequate physical explanation); and functional status as determined by the Medical Outcomes Study Short-form General Health Survey. RESULTS: Each of the 15 common symptoms was frequently somatoform (range, 16% to 33%). The presence of any physical symptom increased the likelihood of a diagnosis of a mood or anxiety disorder by at least twofold to three-fold, and somatoform symptoms had a particularly strong association with psychiatric disorders. The likelihood of a psychiatric disorder increased dramatically with increasing numbers of physical symptoms. The prevalence of a mood disorder in patients with 0 to 1, 2 to 3, 4 to 5, 6 to 8, and 9 or more symptoms was 2%, 12%, 23%, 44%, and 60%, respectively, and the prevalence of an anxiety disorder was 1%, 7%, 13%, 30%, and 48%, respectively. Finally, each physical symptom was associated with significant functional impairment; indeed, the number of physical symptoms was a powerful correlate of functional status. CONCLUSIONS: The number of physical symptoms is highly predictive for psychiatric disorders and functional impairment. Multiple or unexplained symptoms may signify a potentially treatable mood or anxiety disorder. PMID- 7987512 TI - Depression, suicidal ideation, and substance use among adolescents. Are athletes at less risk? AB - OBJECTIVES: To determine the relationship between participation in high school athletic programs and depression, suicidal ideation, and substance use, and to study the high-risk behaviors of suicidal ideation and substance use. DESIGN: Survey. SETTING: A suburban public high school in Kentucky. PARTICIPANTS: We received 823 (80%) responses from 1030 potential respondents. Athletes (ie, participation on a high school athletic team) were compared with non-athletes. MEASURES: Depression was measured by the Children's Depression Inventory by an index of suicidal ideation by an indicator of a past suicide attempt, and by current use of tobacco, alcohol, marijuana, and cocaine. RESULTS: Thirty percent of the sample participate in school athletic teams. Athletes are less depressed, have less suicidal ideation and attempts, and are less likely to currently smoke cigarettes or marijuana. The use of smokeless tobacco and cocaine was not related to athletic participation. After controlling for demographic characteristics, no difference in alcohol use was found between athletes and nonathletes. CONCLUSIONS: Athletic participation is a marker for a decreased likelihood of depression and some high-risk behaviors in adolescents. Future research could help in creating alternative interventions beyond participation in varsity and junior varsity athletic teams. PMID- 7987513 TI - The role of clinical workload and satisfaction with workload in rural primary care physician retention. AB - OBJECTIVE: To examine the relationship between clinical workload and workload satisfaction in rural primary care physician retention. DESIGN: Data from a survey, "Practice Patterns of Young Physicians, 1987: United States," were analyzed. PARTICIPANTS: Data on rural primary care (general or family practice, general internal medicine, or pediatrics) physicians working full time (> 35 h/wk) in clinical care were analyzed (n = 373). MAIN OUTCOME MEASURES: Self reported likelihood of leaving the current practice within the next 2 years. RESULTS: Twenty-five percent of the physicians indicated that they were somewhat or very likely to leave the practice within the next 2 years. The modal reason for the likelihood of leaving was working too many hours (21%). Forty-nine percent of the respondents were dissatisfied with their workload. Those who were dissatisfied with their workload reported a greater likelihood of leaving (P = .0005). However, a quantitative measure of workload was not significantly related to the likelihood of leaving. The results of a multiple regression indicated that employees and those dissatisfied with their workload were most likely to leave the practice within the next 2 years. CONCLUSIONS: Satisfaction with clinical workload is an important factor in the likelihood of retaining rural primary care physicians. PMID- 7987514 TI - National survey on hospital-based privileges in family practice obstetrics. AB - PURPOSES: To document the content and level of obstetrical hospital-based privileges for members of the American Academy of Family Physicians and to describe variations between regions, rural vs urban practices, and various physician characteristics. METHODS: About 12% of the active members of the American Academy of Family Physicians listed as offering obstetrical care by the Academy as of March 1991 were randomly sampled by mailed questionnaire. Samples were drawn from three national regions. Privileges were grouped by degree of restriction, based on whether consultation or transfer was required. RESULTS: Of 1464 surveys mailed, 1026 physicians (70%) responded. Only 740 (72%) stated that they still practiced obstetrics. Privileges ranged from least restricted (100% provided vaginal vertex delivery, with no consultation required) to most restricted (79% provided amniocentesis, with consultation or transfer required). A surprisingly large proportion of physicians reported having fewer routine and more advanced privileges without consultations being required, such as ultrasonography (53%), vaginal breech delivery (41%), and cesarean section (25%). Physicians having more advanced privileges tended to be located in the West or mountain-plains region; be trained in the Midwest, mountain-plains region, or the West; work in middle-sized, nonteaching hospitals in more rural countries; have completed advanced obstetrical training (> or = 6 months); and deliver more than 40 infants per year. CONCLUSIONS: Overall, a considerable number of hospital based obstetrical privileges are granted to family physicians. No uniformity in privileges prevails, owing to significant regional and practice variations. Teaching hospitals reportedly restrict obstetrical care by family physicians more than other hospitals. The variations in restrictions could not be explained by degree of training. PMID- 7987515 TI - Improving a preventive services reminder system using feedback from focus groups. AB - OBJECTIVE: To improve the computer-generated preventive services patient reminder letter used by a department of family medicine at a medical university in South Carolina. DESIGN: A qualitative method chosen because of its demonstrated efficacy in generating in-depth attitude and opinion data was used for 12 focus groups (111 participants) in which participants were asked to evaluate the reminder letter and other preventive services reminder materials. Information from these groups was used to design a revised patient reminder system that was tested in six additional focus groups (50 participants). SETTING: University based family medicine center. PARTICIPANTS: Adults 19 years of age or older of whom approximately one half were selected from a random sample of family medicine center patients and the remainder from volunteers recruited from the general community by newspaper advertisement. INTERVENTIONS: None. MAIN OUTCOME MEASURES: Participants' perceptions and attitudes about the reminder letter and other materials as well as suggestions for improving the preventive services reminder system. RESULTS: The revised patient reminder materials resulted in a warmer, more personal letter sent to patients at the time of their birthdays in an envelope containing a prevention message. A leaflet describing the rationale for preventive services and answering common questions about prevention and a booklet describing the preventive services available at the family medicine center were also developed. CONCLUSION: This study illustrated the benefits of incorporating patients' perspectives in the design of preventive services reminders. PMID- 7987516 TI - The emerging role of vitamins as antioxidants. AB - The recommended dietary allowances for vitamins are designed to estimate the levels of intake needed to prevent known deficiency states in most healthy people. Evidence is now accumulating that some vitamins may have health-promoting benefits in amounts higher than the current recommendations. The antioxidant properties of vitamins may play a role in treating or preventing a variety of disorders, including atherosclerosis, age-related cataracts and macular degeneration, and some cancers. This article reviews the possible risks and benefits of high intakes of antioxidant vitamins, including the controversy about supplementation. PMID- 7987517 TI - The Marfan syndrome. An underdiagnosed killer. AB - The Marfan syndrome is an inherited connective-tissue disorder. The sequela of the syndrome is premature death that is most often due to cardiac complications and that can be prevented with early diagnosis and aggressive management. Although research has identified a gene responsible for the myriad of phenotypic presentations, the diagnosis of Marfan syndrome remains clinical. The family physician is well positioned, with consultation from an experienced cardiac surgeon, to orchestrate the diagnosis and management of the Marfan syndrome. PMID- 7987518 TI - Lower respiratory tract infection with Chlamydia pneumoniae. AB - Chlamydia pneumoniae, also known as TWAR, is a common respiratory pathogen that can cause pneumonia, bronchitis, sinusitis, and pharyngitis. The clinical similarities between C pneumoniae infection and infection with other respiratory pathogens together with the lack, until recently, of readily available diagnostic tests for C pneumoniae have hindered its recognition and treatment in the outpatient setting. In this report, three patients with acute C pneumoniae infection from the Acute Respiratory Disease Study at the University of Washington are described, and the microbiologic characteristics, epidemiologic characteristics, clinical presentations, diagnosis, and treatment of acute C pneumoniae infection are considered. PMID- 7987519 TI - Abstracts of the 17th annual meeting of the European Neuroscience Association and 26th annual meeting of the European Brain and Behaviour Society and the meeting of the Austrian Neuroscience Association. Vienna, 4-8 September 1994. PMID- 7987521 TI - A family of U1 pseudogenes in Bombyx mori may be derived from an ancestral pseudogene. AB - Seven EMBL-4 lambda clones containing U1 small nuclear RNA sequences were isolated from a Bombyx mori genomic library. Six of the seven represent unique sequences. The six unique U1 sequences exhibit fixed point 3'-end truncation. Five out of the six clones share immediate 3'-end flanking sequences while two share 5'-end flanking sequences. Fixed point 3'-end truncation and a hierarchy of shared to unique diagnostic mutations may suggest a family of U1 pseudogenes generated from a reverse-transcribed class II pseudogene in B. mori. An ancestral 'master' U1 pseudogene capable of RNA- and/or DNA-mediated transposition may give rise to generations of U1 pseudogenes that include the original pseudogene's flanking sequences. Identical 3'-end truncation in some of these U1 sequences can be explained by RNA self-priming due to intra-strand binding prior to reverse transcription. PMID- 7987520 TI - An estimate of the number of serine protease genes expressed in sheep blowfly larvae (Lucilia cuprina). AB - A large and diverse family of serine protease genes was identified in first instar larval cDNA of the sheep blowfly (Lucilia cuprina). This complex repertoire of genes was identified via a PCR approach using highly degenerate primers based on structurally conserved regions which surround the active site His and Ser residues found in all serine proteases. PCR products from entire first-instar larval cDNA, or from third-instar larval salivary glands or cardia, generated using a microscale RT-PCR method, were cloned into a plasmid vector. Comparison of the restriction fragment patterns of PCR products generated from the three different sources suggests a highly diverse tissue-specific pattern of serine protease expression in this organism. Detailed analysis of the restriction fragment patterns of sixty-nine randomly selected clones from entire first-instar larvae revealed forty-nine different classes of PCR product. Maximum likelihood analysis of these data indicate that between 125 and 220 different serine protease genes are expressed in first-instar larvae of L. cuprina. DNA sequence analysis of ten randomly-selected clones, derived from the three tissue sources, indicated that all ten encoded serine protease gene fragments. A frequently occurring PCR product, generated from both first-instar total cDNA and third instar cardia cDNA, showed 73% amino acid identity to a digestive protease expressed in Drosophila melanogaster larval gut cells. PMID- 7987522 TI - Molecular characterization of a strain-specific repeated DNA sequence in the fall armyworm Spodoptera frugiperda (Lepidoptera: Noctuidae). AB - The fall armyworm moth, Spodoptera frugiperda, is a migratory species composed of sympatric corn and rice strains. The strains are indistinguishable in morphology but can be recognized by molecular markers. We have cloned and characterized seven monomer units of a repeated DNA sequence, called FR, which is found exclusively in the genome of the rice strain individuals. The 189 bp FR units are tandemly organized in arrays longer than 30 kb. Female individuals possess over 100-fold more of the FR sequence than male individuals. The repeated sequence is not methylated at GGCC sites, and shows high sequence similarity among repeat units. PMID- 7987523 TI - Chromosomal mapping of two loci affecting filarial worm susceptibility in Aedes aegypti. AB - Two quantitative trait loci (QTL) affecting susceptibility of the mosquito Aedes aegypti to the filarial worm parasite Brugia malayi were identified using restriction fragment length polymorphism (RFLP) markers. The first locus, fsb[1,LF178], resides within a 10 cM interval on chromosome 1 and exhibits a recessive effect with respect to susceptibility. The second locus, fsb[2,LF98], resides within a 9 cM interval on chromosome 2 and exhibits an additive effect on susceptibility. Significant epistasis was detected between these loci, although the effect of fsb[2,LF98] was dependent on the genetic background of the mosquito strains. Suggestions for a standard QTL nomenclature are included. PMID- 7987524 TI - Evolutionary origin of whiteflies (Hemiptera: Sternorrhyncha: Aleyrodidae) inferred from 18S rDNA sequences. AB - Phylogenetic analysis of 18S rDNA nucleotide sequences of hemipteran exemplars shows Sternorrhyncha (psyllids, whiteflies, aphids and scales) is monophyletic and forms a sister group to all other hemipterans (Euhemiptera). Whiteflies form a sister group to all other Sternorrhyncha. Primary structures of 18S rDNAs of all sternorrhynchans are exceptionally long (approximately 2200 to approximately 2500 bp) due to internal expansions. These expansions are a synapomorphy of Sternorrhyncha; other hemipterans possess shorter 18S rDNAs (approximately 1900 to approximately 1925 bp). The 18S rDNA of whiteflies is the longest recorded to date and has a base substitution rate of approximately 3 times greater than Euhemiptera taxa examined. The relevance of these findings to the fossil record, feeding strategies, reproductive biologies, and geoclimatic distribution is discussed. PMID- 7987525 TI - Expression of polydnavirus genes from the parasitoid wasp Cotesia kariyai in two noctuid hosts. AB - DNA purified from polydnavirus particles isolated from the parasitoid wasp Cotesia kariyai contained double-stranded closed circular molecules which were polydisperse in molecular weight. 2 days after viral injection into the host armyworm larvae viral DNA was detected in all tested larval tissues, including haemocytes, fat body, nerve cord and brain. Viral transcripts were also observed in all the tissues of virus-injected larvae. The most specific tissue was haemocytes because more viral DNA and RNA was detected than in the other tissues. Viral transcripts were not detected in haemocytes of virus-injected larvae of common cutworm. The present data suggest that C. kariyai virus (CkV) gene expression occurs species-specifically, although viral DNA can be detected in all tested tissues of the habitual host armyworm. PMID- 7987526 TI - Clinical and electrophysiologic features of syncope in chronic chagasic heart disease. AB - INTRODUCTION: Syncope in patients with chronic Chagasic heart disease (CCHD) is a frequent but poorly studied problem. METHODS AND RESULTS: Fifty-three patients with CCHD and recurrent syncope were followed for 2 to 127 months. They were classified into the following groups: G-I (n = 15) without inducible ventricular tachycardia (VT) and normal HV interval; G-II (n = 17) with only inducible VT; G III (n = 11) with only an abnormal HV interval; and G-IV (n = 10) with both an inducible VT and an abnormal HV interval. Empiric pharmacologic therapy was given in G-I; pharmacologic therapy guided by electrophysiologic study in G-II; atrioventricular pacing in G-III; and empiric pharmacologic with atrioventricular pacing in G-IV. Age and sex were similar among groups; New York Heart Association Functional Class I symptoms were more prevalent (P = 0.0001) in G-I. The ejection fraction by echocardiography was higher in G-I (P = 0.0122). The density of premature ventricular complexes by Holter monitoring was similar among groups. The complexity of premature ventricular complexes by Holter was significantly higher in G-II (P = 0.0270); this variable, analyzed from the exercise electrocardiogram, was not different among groups. All deaths were sudden, prevalence was higher in G-II and absent in G-III, and recurrence of syncope was similar among groups. CONCLUSION: The most probable causes of recurrent syncope were VT (43%) with poor prognosis, and paroxysmal atrioventricular block (21%) with a favorable prognosis. Absence of congestive heart failure, complexity of premature ventricular complexes by Holter, and absence of intraventricular heart block showed statistical correlation with normal electrophysiologic study, inducible VT, and normal HV interval, respectively. PMID- 7987527 TI - The effects of lidocaine on the vulnerable period during ventricular fibrillation. AB - INTRODUCTION: It was postulated that a subthreshold defibrillation shock failed to halt ventricular fibrillation because the shock itself reinitiated ventricular fibrillation by falling into the vulnerable period of the wavefronts. Whether or not the timing of the vulnerable period is determined by the ventricular fibrillation cycle length is unknown. METHODS AND RESULTS: We determined the patterns of epicardial activation in ten dogs by computerized mapping techniques during unsuccessful defibrillation. Lidocaine was then given to prolong the ventricular fibrillation cycle length, and the computerized mapping studies were repeated. The results showed that lidocaine increased the ventricular fibrillation cycle length from 110 +/- 13 msec to 156 +/- 5 msec (P < 0.001). Among 55 episodes of unsuccessful defibrillation, the site of the earliest postshock activation occurred in the center of the mapped tissue 12 times at baseline and 14 times during lidocaine infusion. At electrodes that registered as postshock early sites, the preshock intervals clustered within a narrow range both before (58 +/- 14 msec) and during (101 +/- 18 msec, P < 0.001) lidocaine infusion. The correlation between the preshock intervals and the ventricular fibrillation cycle length was significant for these 26 sites (r = 0.87, P < 0.001). CONCLUSION: We conclude that a vulnerable period is present during ventricular fibrillation, and the timing of the vulnerable period is determined by the ventricular fibrillation cycle length. PMID- 7987528 TI - A prospective randomized cross-over comparison of mono- and biphasic defibrillation using nonthoracotomy lead configurations in humans. AB - INTRODUCTION: For current implantable defibrillators, the nonthoracotomy approach to implantation fails in a substantial number of patients. In a prospective randomized cross-over study the defibrillation efficacy of a standard monophasic and a new biphasic waveform was compared for different lead configurations. METHODS AND RESULTS: Intraoperatively, in 79 patients receiving nonthoracotomy defibrillation leads, the defibrillation threshold was determined in the initial lead configuration for the mono- and biphasic waveform. In each patient, both waveforms were used alternately with declining energies (20, 15, 10, 5 J) until failure of defibrillation occurred. Three different initial lead configurations were tested in different, consecutive, nonrandomized patients using a bipolar endocardial defibrillation lead alone (A; n = 36) or in combination with a subcutaneous defibrillation patch (B; n = 24) or array (C; n = 19) lead. The lowest successful defibrillation energy with the biphasic waveform was less than, equal to, or higher than with the monophasic waveform in 64%, 28%, and 8% of patients, respectively, and on average significantly lower with the biphasic waveform for all three lead configurations (A: 11.3 +/- 4.4 J vs 14.5 +/- 4.5 J; B: 9.7 +/- 4.7 J vs 15.1 +/- 4.5 J; C: 7.9 +/- 4.5 J vs 12.4 +/- 4.9 J). Defibrillation efficacy at 20 J was significantly improved by the biphasic waveform (91% vs 76%). CONCLUSION: In combination with nonthoracotomy defibrillation leads, the biphasic waveform of a new implantable cardioverter defibrillator showed superior defibrillation efficacy in comparison to the standard monophasic waveform. Defibrillation thresholds were improved for lead systems with and without a subcutaneous patch or array lead. PMID- 7987529 TI - Lack of evidence for low-dimensional chaos in heart rate variability. AB - INTRODUCTION: The term chaos is used to describe erratic or apparently random time-dependent behavior in deterministic systems. It has been suggested that the variability observed in the normal heart rate may be due to chaos, but this question has not been settled. METHODS AND RESULTS: Heart rate variability was assessed by recordings of consecutive RR intervals in ten healthy subjects using ambulatory ECG. All recordings were performed with the subjects at rest in the supine position. To test for the presence of nonlinearities and/or chaotic dynamics, ten surrogate time series were constructed from each experimental dataset. The surrogate data were tailored to have the same linear dynamics and the same amplitude distribution as the original data. Experimental and surrogate data were then compared using various nonlinear measures. Power spectral analysis of the RR intervals showed a 1/f pattern. The correlation dimension differed only slightly between the experimental and the surrogate data, indicating that linear correlations, and not a "strange" attractor, are the major determinants of the calculated correlation dimension. A test for nonlinear predictability showed coherent nonlinear dynamic structure in the experimental data, but the prediction error as a function of the prediction length increased at a slower rate than characteristic of a low-dimensional chaotic system. CONCLUSION: There is no evidence for low-dimensional chaos in the time series of RR intervals from healthy human subjects. However, nonlinear determinism is present in the data, and various mechanisms that could generate such determinism are discussed. PMID- 7987530 TI - A neural network system for detection of atrial fibrillation in ambulatory electrocardiograms. AB - INTRODUCTION: A neural network classifier has been designed, which is able to distinguish atrial fibrillation (AF) from other supraventricular arrhythmias in ambulatory (Holter) ECGs. METHOD AND RESULTS: The classification algorithm uses a rhythm analysis that considers the ECG to be a time series of RR interval durations. This is combined with an analysis of baseline morphology that considers the morphological characteristics of the non-QRS portions of the waveform. A backpropagation-based neural network has been used as part of the classifier implementation. When applied to a library consisting exclusively of 42,970 examples of AF and other supraventricular rhythm disturbances validated by an experienced cardiologist, the algorithm demonstrated a sensitivity of 82.4% for 10-beat runs of paroxysmal atrial fibrillation (PAF) and a specificity of 96.6%. Since this system has been implemented as a postprocessor to a conventional automated Holter system, operating only on segments of ECG that are known to contain supraventricular arrhythmias rather than ventricular arrhythmias or sinus rhythm, it can be added to most existing Holter processing systems without significantly increasing the average time to process a tape. CONCLUSION: A neural network system has been designed, which can potentially provide, for the first time, an accurate, quantitative technique to determine the natural history of PAF and to evaluate potential treatments for PAF. PMID- 7987531 TI - Early afterdepolarization formation in cardiac myocytes: analysis of phase plane patterns, action potential, and membrane currents. AB - INTRODUCTION: Early afterdepolarizations (EADs) are among the mechanisms proposed to underlie ventricular arrhythmias. Sea anemone toxin, ATXII, known to delay Na inactivation and to induce plateau level voltage oscillations, was used to study the formation of EADs. METHODS AND RESULTS: Action potential and membrane currents were studied in rat ventricular myocytes using whole cell current and voltage clamp techniques. Phase plane trajectories were generated by plotting membrane potential (V) versus the first time derivative of membrane potential (dV/dt). Under current clamp conditions, ATXII (40 nM) consistently prolonged the action potential and induced EADs. The EADs developed at a plateau voltage between -10 and -40 mV. Calcium channel blockers, verapamil 10 microM and cobalt 4 mM, and the sarcoplasmic reticulum modulator, ryanodine (1 microM), did not antagonize ATXII effects on the action potential and EADs. However, Na channel blockers, tetrodotoxin 0.3 microM and lidocaine 40 microM, and rapid stimulation consistently shortened the prolonged action potential and suppressed EADs. Under voltage clamp conditions in the presence of ATXII, a slowly decaying inward current followed the fast inward current during depolarizing pulses. Membrane currents flowing at or later than 100 msec after the test pulse were analyzed. The control isochronal current-voltage (I-V) curves showed no late inward currents. In the presence of ATXII, all the isochronal I-V curves showed an inward current that was more prominent between -40 and 0 mV. The ATXII-induced current at the 100-msec isochrone activated at a potential of approximately -60 mV, peaked at about -20 mV, and reversed at +40 mV consistent with the Na current I-V curve. The isochronal I-V curves obtained after lidocaine superfusion resembled those of the control. The phase plane trajectory of the action potential obtained with ATXII showed an oscillatory behavior corresponding to the EAD range of potential; within this voltage range, the isochronal I-V curves were shown to cross the abscissa three times instead of once. CONCLUSION: These results suggest that, in this experimental model, neither sarcolemmal L-type Ca current nor sarcoplasmic reticulum Ca release plays a significant role in the genesis of ATXII-induced EADs. EADs are generated by a voltage-dependent balance between a markedly prolonged Na inward current and K outward currents within the voltage plateau range of the action potential but not by Ca current reactivation and inactivation. PMID- 7987532 TI - The future of arrhythmia surgery. AB - The future of arrhythmia surgery is discussed in light of the 25 years of historical developments that have led to the present explosion in antiarrhythmic therapies and technologies. The role of the arrhythmia surgeon in these developments is outlined, along with a number of exciting near-term and far-term developments that will continue to revolutionize therapeutic interventions for arrhythmia problems. PMID- 7987533 TI - Stories about the origin of quinquina and quinidine. PMID- 7987534 TI - Requirements for growth and differentiation of a human colonic adenocarcinoma cell line. PMID- 7987535 TI - Prolonged hypoxia increases pulmonary vascular smooth muscle cytosolic calcium. PMID- 7987536 TI - Limitations of cell culture of airway epithelium collected by a nasal brushing technique. PMID- 7987537 TI - Serum-free culture of rat keratinocytes. AB - Procedures for the serum-free culture of rat keratinocytes have been established. Basal cells prepared from epidermis of newborn rat were stored in liquid nitrogen and used for primary culture. Among the available media, MCDB 153, developed originally for human keratinocyte (HK) culture, was the best for the development of serum-free formulation. To grow rat keratinocytes, bovine serum albumin was arbitrarily substituted for the macromolecule supplements needed for HK culture, i.e. fetal bovine serum protein or bovine pituitary extract. Qualitative and quantitative adjustment of supplements was thereafter made to support rapid cell growth. Satisfactory cell growth was achieved in the optimized medium of MCDB 153 supplemented with growth factors and amino acids: insulin (10 micrograms/ml), hydrocortisone (0.1 microgram/ml), epidermal growth factor (25 ng/ml), calcium chloride (0.2 mM), histidine (0.23 mM), isoleucine (0.05 mM), tryptophane (0.015 mM), threonine (1.25 mM), tyrosine (0.031 mM), alanine (4.08 mM), and albumin (2 mg/ml). This optimized culture system was superior to the original HK culture condition for rapid growth of rat keratinocytes. Under our condition, cells grew as a monolayer, becoming confluent, but without stratification, and were passaged 2 to 3 times without any changes in morphology. The serum-free formulation allows us to control more accurately the concentrations of biomolecules in the medium including lipids and hormones, and therefore will be suitable for the study focusing on lipid metabolism or hormonal regulation of rat keratinocytes. PMID- 7987538 TI - A "coupled" subchondral bone-articular cartilage tissue culture system for the study of cartilage proteoglycan metabolism. AB - Current evidence suggests that interactions between the subchondral bone and the articular cartilage of mammalian diarthrodial joints may occur through the action of bone-associated peptide factors. However, there is no suitable organ culture model for studying these interactions. This study defines a long-term tissue culture system where the articular cartilage is coupled to the adjacent subchondral bone obtained from the proximal ends of bovine metacarpals. Autoradiography done over 3 mo., by utilizing [35S]SO4 incorporation into cartilage proteoglycan (PG) and a procedure for cutting non-decalcified bone, demonstrated similar numbers of silver grains over chondrocytes in all cartilage zones, including the bone-cartilage interface. Newly synthesized PG (NSPG) from the cartilage of the "coupled" system over a 3-wk period was primarily of large hydrodynamic size (Kav of 0.34). Comparable bovine articular and nasal cartilage slice systems, incubated for short periods of time, yielded similar and somewhat larger NSPG, respectively. Labeled chondroitin sulphate PG accumulating in the medium of primary chondrocyte monolayer cultures, derived from the cartilage of the coupled system at 0, 1, 2, and 3 wk, revealed two polydisperse subpopulations (Kav of 0.30 to 0.38 and 0.51 to 0.68). We conclude that this coupled bone cartilage system is viable for prolonged periods, is suitable for studies on the metabolism of articular cartilage PGs, and seems to have some advantages over the cultured articular cartilage slice system. PMID- 7987540 TI - Immature mouse uterine tissue in organ culture: estrogen-induced growth, morphology and biochemical parameters. AB - Although estrogens have been shown to stimulate a variety of morphologic and biochemical changes in the uterus in vivo, no clear consistent demonstration of similar responses in vitro have been made; thus, a defined organ culture system using the immature mouse uterus was established to study the possibility of demonstrating estrogenic responses in vitro. Uterine tissue from immature outbred mice (17 to 24 days of age) were cut crosswise in 1-mm3 coins and cultured in a defined medium in the absence of serum, phenol red, or growth factor supplements. Diethylstilbestrol (DES), a synthetic estrogen, was added to the media at doses ranging from 1 to 100 ng/ml. The effect of DES on uterine cell proliferation was assessed by morphologic changes in uterine epithelial and stromal cells, increase in number of epithelial cells per unit basement membrane, increase in height of luminal epithelial cells, and [3H]thymidine incorporation. Functional changes were determined by measuring the amounts of the estrogen-inducible uterine protein, lactoferrin, that was localized in the epithelial cells and secreted into the media, and the localization of the estrogen receptor in the cultured tissues. Results indicate that under the described conditions of culture, estrogens like DES can induce morphologic and biochemical responses in the uterus that are similar to those seen in vivo. This organ culture system will aid in the investigation of various mechanisms involved in the hormonal regulation of growth and differentiation of estrogen target tissues. PMID- 7987539 TI - Lymphangiogenesis in vitro: formation of lymphatic capillary-like channels from confluent monolayers of lymphatic endothelial cells. AB - Lymphatic endothelial cells grown long term in culture form lymphatic capillary like tubes. Examination by light and transmission electron microscopy showed that these structures were closed loops composed of one to several cells connected by intercellular junction to form a luminal space. This first demonstration of lymphangiogenesis in confluent monolayer cultures of lymphatic endothelial cells (a) showed that collagen type I accelerated lymphatic capillary tube formation, whereas fibronectin and matrigel had no effect; b) provided a model to study lymphatic endothelial cell function and differentiation; and c) offered a possibility to distinguish differences between the process of lymphangiogenesis and angiogenesis by testing various factors and conditions that effect endothelial cell behavior. PMID- 7987541 TI - Extracellular matrix and mouse mammary cell function: comparison of substrata in culture. AB - Cultured mammary cells depend on interaction with a substratum for functional differentiation, even in the presence of lactogenic hormones. Protein synthesis and secretion by mouse mammary epithelial cells on floating collagen gels and (EHS) matrix were compared. Cells were prepared by collagenase digestion of tissue from mid-pregnant mice. Protein synthesis was consistently greater in cells attached to EHS matrix, and was associated with proportionately higher rates of protein secretion into culture medium. Cells on EHS secreted protein into a luminal space formed within multicellular alveolus-like structures. Luminal secreted protein, extracted by EGTA treatment of cells in situ, constituted up to 40% of total secreted radiolabeled protein for cells on EHS matrix. The EGTA extract contained a higher proportion of casein and lactoferrin, whereas transferrin was predominantly in the medium. This indicated that cells on EHS matrix had become polarized and were secreting proteins vectorially. In contrast, EGTA treatment of cells on floating collagen gels released virtually no radiolabeled protein, showing that mammosphere formation was a property of cells on EHS. These biochemical observations were supported by ultrastructural evidence. In EHS cultures, the proportion of secreted protein in the luminal fraction, but not the distribution of secreted proteins, changed with time. This suggests that there may be leakage out of the lumen, or intraluminal degradation of protein after secretion. Nevertheless, the results suggest that cellular organization into mammospheres on EHS matrix promotes synthetic and secretory activity. This system provides a useful model for investigation of the regulation of milk secretion. PMID- 7987542 TI - [The current situation of tuberculosis in Spain]. PMID- 7987543 TI - [The usefulness of serum neuron-specific enolase in the clinical management of small-cell lung carcinoma]. AB - The utility of neuron-specific enolase (NSE) for the diagnosis and management of small cell lung cancer (SCLC) is analyzed. Serum concentrations of NSE were measured in 69 healthy adults, 106 patients with non-neoplastic pneumopathy (NNP), 16 with pulmonary metastasis of extrapulmonary origin (PMEO), 126 with non small cell lung cancer (NSCLC), and 77 with SCLC. Repeated analyses were carried out for patients in the last group during and after treatment, and survival time was recorded. NSE was high in 77.6% of patients with SCLC [50% in cases with limited disease (LD) and 93.6% in those with extensive disease (ED)]. NSE was high in 10.3% of those with NSCLC, in 11.5% of those with PMEO, and in 2.8% of those with NNP. NSE decreased 100% in SCLC patients achieving full remission after treatment and in 25% of those responding poorly. Later, this marker increased in 81.2% of those experiencing relapse, and in 6.2% of these the increased preceded symptoms. Initial NSE concentrations had prognostic value (p = 0.003) that was independent of disease stage (LD or ED). NSE is of great diagnostic and prognostic value in SCLC, accurately reflecting tumor size. Posttreatment changes closely parallel disease activity. PMID- 7987544 TI - [The gammagraphic diagnosis of acute pulmonary thromboembolism]. AB - We aimed to determine the prevalence of acute pulmonary embolism (APE) in our population and to establish the diagnostic reliability of pulmonary scintigraphy (PS), as well as the influence of the clinical context (CC). During a 2-year prospective study, patients were diagnosed by either pulmonary angiography or normal-perfusion PS. A diagnosis of APE was made in 73 (75%) of a total of 97 patients. In the group of 58 patients diagnosed by ventilation/perfusion (V/Q) PS, 33 were classified as "highly probably" having APE; 32 of these in fact had the syndrome (sensitivity 88%, specificity 94%). Combining the "highly probable" patients with the "highly suspected" patients diagnosed by ventilation/perfusion PS, we obtained a sensitivity of 51% and specificity of 100%. Ventilation scintigrams were unobtainable in 28 older patients with greater dyspnea and tachypnea, who were unable to perform the maneuvers. Of the 21 "highly probable" patients as assessed by PS, 19 were diagnosed as having APE (sensitivity 86%, specificity 85%). Combining the "highly probable" patients with the "highly suspected" group, we obtained a sensitivity of 32% and specificity of 100%. Normal perfusion PS excludes clinically relevant APE. "Intermediate" or "slight" probability PS results, even when combined with CC, have no diagnostic validity. PMID- 7987545 TI - [A decrease in the level of CPAP required after prolonged treatment in patients with the obstructive sleep apnea syndrome]. AB - Application of continuous positive upper airway pressure (CPAP) is the treatment of choice in obstructive sleep apnea syndrome (OSAS). CPAP keeps the upper airway open by providing a "pneumatic splint" on the pharyngeal walls. However, it has been suggested that prolonged nasal CPAP treatment may also improve the physiopathological mechanisms responsible for OSAS by a variety of mechanisms such as the reduction of edema of the pharyngeal mucosa, modification of upper airway muscle dynamics; there may even be a reduction in the intensity of phenomena responsible for brief awakening and ending of apneic episodes. The objective of this study was to determine whether prolonged nasal CPAP is associated to a reduction of CPAP pressure required for eliminating apnea in patients with OSAS. We studied 22 patients (4 women) with OSAS diagnosed by conventional polysomnography, including study of neurological variables during sleep (electroencephalogram, ocular movement, submental electromyogram), respiratory variables (nasal air flow, thoracic-abdominal movement, O2 saturation in the blood), and others (electrocardiogram, leg movement). Treatment was exclusively with nasal CPAP. All 22 patients were middle-aged (52.3 +/- 10 years), presented a mean apnea/hypoapnea index of 65.2 +/- 24 per hour. CPAP levels needed to eliminate episodes of apnea, blood O2 desaturation and snoring at the time of diagnosis and after long-term treatment (8.5 +/- 4.6 months) were applied. Weight was recorder at both measurement times. Eighteen of the 22 patients (1 woman, mean age 53.1 +/- 11.4 years and apnea/hypopnea index 64.8 +/- 23.4 per hour) experienced no weight change during treatment.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7987546 TI - [Brief polysomnographic studies in the diagnosis of the obstructive sleep apnea syndrome]. AB - Firm diagnosis of obstructive sleep apnea syndrome (OSAS) is normally based on all-night-long polysomnograms, at considerable expenditure of time and money. Shorter studies have been proposed as an alternative. We have assessed the efficacy of polysomnograms recorded over the first three hours of nocturnal sleep (SN) for diagnosing OSAS and the results have been compared with those of polysomnograms recorded throughout the entire night (EN). Twenty-five male patients suspected of having OSAS were enrolled; 19 were diagnosed for OSAS by EN and 16 were diagnosed by SN, indicating 3 false negatives and a sensitivity of 84% for SS. No false positives were obtained by studying only the first three hours of sleep, indicating a specificity of 100%. Significant differences were found in minimum oxygen saturation (SatO2) and percent of total sleep time with intervals of SatO2 below 80%. We conclude that polysomnography during the first part of nocturnal sleep is a specific method for screening for OSAS and that, although this method's sensitivity is high, study should be continued throughout an entire night when results are negative. Desaturation levels may be underestimated in recordings lasting only the first half of the night. PMID- 7987547 TI - [Arterial puncture in Spain. A follow-up of the SEPAR 1987 guideline. Sociedad Espanola de Neumologia y Cirugia Toracica]. AB - This study sought to evaluate the procedures used for measuring arterial gases in our hospitals and determine the level of compliance with the 1987 SEPAR guidelines. Questionnaires covering the obtention, transport, storage and analysis of samples, as well as familiarity with the guidelines were distributed to 150 pneumology, internal medicine, intensive care and emergency services; 78 centers responded (71% from pneumology departments). General information obtained was as follows: arterial puncture is carried out by nurses without anesthesia and using syringes for gases; the radial artery is used; with post-puncture pressure provided by the patient; the sample is analyzed within 15 minutes and cold storage is used. The department's own automatic analyzer is used. Buffered gases and solutions are used for calibration and quality control measures are rare. Some aspects of the guidelines are unfamiliar. We believe that an effort should be made to extend application of the guidelines in order to improve arterial blood gas analysis. PMID- 7987548 TI - [Corticoids in chronic obstructive pulmonary disease]. PMID- 7987549 TI - [Mediastinal chordoma]. AB - We describe a patient with chordoma located in the mid-posterior mediastinum whose first clinical symptoms were respiratory. This, together with the patient's age at presentation, made this case unusual. PMID- 7987550 TI - [Follicular bronchiolitis: an infrequent cause of interstitial pneumopathy]. AB - A 63-year-old woman with follicular bronchiolitis presenting as diffuse interstitial pneumopathy is described. Diagnosis was made by open lung biopsy and the patient was treated in our department until death. The course of disease and response to treatment was similar to that observed in cases of idiopathic pulmonary fibrosis. No associated collagen disease was found. This report reviews the histological and clinical signs of this disease, as well as treatment. PMID- 7987551 TI - [Horner's syndrome associated with a solitary bone plasmacytoma of the first rib]. AB - A case of solitary plasmacytoma originated in the left first rib in a 45-year male is presented. The initial symptomatology was a Horner's syndrome. A chest X ray, gammagraphy, TAC and arteriography showed a tumor shadow in the left chest wall; no evidence of plasmacytoma after clinical study found use where. The treatment was surgical excision and postsurgical radiotherapy. The histological investigation revealed a plasmacytoma of the rib. The patient have been followed for two years. The patient is asymptomatic, without evidence of local recurrence and systemic spread of the disease two years after treatment. PMID- 7987552 TI - [Chronic eosinophilic pneumonia. An analysis of 4 cases]. AB - Chronic eosinophilic pneumonia (CEP) is characterized by non-specific clinical presentation, interstitial radiological signs, peripheral acini and pulmonary infiltration by eosinophils, accompanied or not by peripheral eosinophilia. Response to treatment with steroids is spectacular. We describe 4 patients with CEP, one diagnosed by response to treatment and the others by bronchoalveolar lavage (BAL). No patient had asthma; 1 also had peripheral eosinophilia. All received long-term treatment with steroids, and there were no relapses. Response to treatment was slow in 2 patients, but obliterans bronchiolitis with or without organizing pneumonia could not be demonstrated. We emphasize the safety and efficiency of BAL for diagnosis of CEP. PMID- 7987553 TI - [Sternal tuberculosis as a unique manifestation of the disease]. PMID- 7987554 TI - [The validation of different criteria for the interpretation of forced spirometry. A preliminary study]. PMID- 7987555 TI - [The prevalence of asthma among the Spanish athletes participating in the Barcelona Olympic Games]. PMID- 7987556 TI - [Problems and perspectives of international unification of methods for measurement of industrial aerosols ]. AB - Having considered disagreements between measurements of industrial aerosols, the authors first performed comparative quantitative analysis of MACs existing in Russia and foreign norms according to International Labour Organization (1990). The article suggests a method to correlate approximately maximal single and average shift concentrations of inhaled and respirable dust in TWA and STEL. PMID- 7987557 TI - [Long-term effect of coal and rock dust on the changes of some biochemical parameters in miners]. AB - The study revealed those changes in connective tissue components and validity of alveolar macrophages in bronchial lavage, which were in correlation with duration and severity of exposure to coal and rock dust. The data proved that roentgenologio changes in the lungs are preceded by changed quantity of viable alveolar cells, higher content of hexauronic acids and hexoses associated with proteins. The stated biochemical tests could be applied to early diagnosis in individuals prone to pneumoconiosis. PMID- 7987558 TI - [Prevention of respiratory tract diseases in polishers of glass products]. AB - The article presents physical and chemical characteristics of dust appearing due to the polishing of glass products. Clinical examination of glass polishers revealed occupational respiratory diseases. The results helped to put into practice the devices to catch humid aerosol and improved equipment for mechanical processing of crystal, to suggest prophylactic measures for the occupational diseases. PMID- 7987559 TI - [Method of comparative evaluation of cytotoxicity of low-soluble dust by lowered activity of 5-nucleotidase in macrophage culture]. AB - The authors suggest a new method to evaluate cytotoxicity of silicosis-dangerous dust through lowered activity of 5'-nucleotidase, a marker of cytolemma, in macrophageal culture. The scientists used the new method to compare cytotoxicity of 4 groups of industrial dust and correlated the results with those obtained in the test of lowered viability of macrophages (by incorporation of trypan blue). Both tests appeared to have correlation of the dust ranks according to cytotoxicity grade. Damage and activation of macrophages by products of their destruction change the cytotoxicity grade in the same direction, so the results could be considered more easily than for the tests where the changes are in opposite directions. PMID- 7987560 TI - [Effectiveness of glutamate in the treatment of early manifestations of occupational fluorosis]. AB - Efficiency of glutamic acid for therapy of early signs of occupational fluorosis was studied in workers engaged into cryolite production. The study proved that use of glutamic acid in occupational conditions prevents progressing of metabolic disorders. The results encourage recommendations to include glutamate into therapeutic and prophylactic nutrition of workers exposed to fluor compounds, into nutritive additions according to special recipe. PMID- 7987561 TI - [Correlation and allergenicity of industrial substances and their chemical structure]. AB - Allergic effects of 575 various chemicals were studied. 20.9% of the chemicals were industrial allergens, 13.6%--mild sensitizers, and 65.5% of substances had no such effects. Allergic properties appeared to depend not on so-called "allergenic" groups, but on interaction between active radicals and all structures of molecule. Sensitization in this case occurs mainly due to properties of the main structure determining common features of all chemical class, secondary elements of the molecule conditioned the intensity of specific effects. PMID- 7987562 TI - [Program and teaching course "Hygienic and epidemiologic aspects of accidents"]. PMID- 7987563 TI - [Structure of working conditions in occupation having privileges according to the List #1 and #2]. AB - The scientists studied work conditions of workers at KAMAZ plants. The studies covered the workers which are assigned to Registers 1 and 2 providing preferential pensions for hazardous and hard work conditions. Although being empirically formed, the Registers include workplaces which are similar in some characters. Therefore the descriptions of work conditions are obtained, and the principles are suggested to provide preferential pensions for workers which are not included into the Registers. PMID- 7987564 TI - [Occupational safety in work with firefighting aerosols]. PMID- 7987565 TI - [Evaluation of plutonium inhalation with weight load method]. PMID- 7987566 TI - [Effect of red phosphorus on microsomal liver oxidative system in rats]. PMID- 7987567 TI - [Standardization of carbon fluoride aerosols in the air of the working area]. AB - Hygienic studies were conducted by means of pilot industrial plant for production of carbon tetrafluoride fibers (CTF). The studies proved that the main hazards of the production are CTF dust and hydrogen fluoride. Average shift concentrations of CTF dust in tne air of workplace equal 0.6-1.5 mg/cu m which 2 times higher than the MAC for HF at all technologic sites except for reactor compartment. The workers servicing the plant demonstrate higher urinary fluor excretion mostly due to HF intake. Experimental studies showed that CTF have low cytotoxicity and fibrogenic activity, these chemicals are assigned to IV jeopardy class (mild hazards). If applied on skin, CTF are absorbed and induce slight local irritation. The MAC for CTF in the air of workplace is set at 6 mg/cu m. PMID- 7987569 TI - User involvement--without the bruises. PMID- 7987568 TI - [Experimental study on risk factors of pneumoconiosis caused by dust in the industry of new construction materials containing glass and coal waste]. AB - The study compared cytotoxicity and fibrogenic ability of quartzitic dust to that appearing at 3 sites of light building filler production based on ground glass or clinker. Obtained results prove possible pneumoconiosis development caused by exposure to such dust types, especially in the production using ground glass. The MAC in this type of production is 2 mg/cu m, for the dust in production using clinker the MAC is 4 mg/cu m. PMID- 7987570 TI - Get a purchase on quality care. PMID- 7987573 TI - Attendance management. PMID- 7987572 TI - Programmed to succeed. PMID- 7987571 TI - Lessons of LIG. Interview by John Naish. PMID- 7987574 TI - Flawed above. PMID- 7987575 TI - Stand up and count. PMID- 7987576 TI - The quality leaders. PMID- 7987577 TI - Generic engineering. PMID- 7987578 TI - Langlands: agenda for nurse leaders. Interview by John Naish. PMID- 7987579 TI - New learning for the new leaders. PMID- 7987580 TI - Pliant for clients? PMID- 7987581 TI - Trust-worthy nurses? PMID- 7987582 TI - Nursing research gets de-based. PMID- 7987583 TI - The costs of nurse absence. PMID- 7987584 TI - Training on the fast track. PMID- 7987585 TI - Grow your own staff. PMID- 7987586 TI - Let's stick together. PMID- 7987587 TI - Many trusts are failing to define the specific nature of their nursing directors' roles. PMID- 7987589 TI - A vanishing vision? PMID- 7987588 TI - Chris Halek--the weigh forward. Interview by John Naish. PMID- 7987590 TI - Change incorporated. Interview by John Naish. PMID- 7987591 TI - Project succeed. PMID- 7987592 TI - Where do your staff go? PMID- 7987593 TI - The price of going public. PMID- 7987594 TI - Complaints that just refuse to go away. PMID- 7987595 TI - At the front of the NVQ. PMID- 7987597 TI - Cheap chips with everything. PMID- 7987596 TI - Put the gem in stratagem. PMID- 7987598 TI - The employment of many more nurses in purchasing posts. PMID- 7987599 TI - Image make-overs. Tips for the tops? PMID- 7987600 TI - Knowledge based--not blindly biased. PMID- 7987601 TI - Paying for performance. PMID- 7987602 TI - Why your budget doesn't add up. PMID- 7987603 TI - Cash in the community. PMID- 7987604 TI - Chains for the better. PMID- 7987605 TI - Teaching in turmoil. PMID- 7987606 TI - Vox pop purchasing. PMID- 7987607 TI - Look who's sorry now. PMID- 7987608 TI - Mixing healthcare with economics. PMID- 7987609 TI - An infectious argument. PMID- 7987610 TI - Numbers nonsense. PMID- 7987611 TI - The risk business. PMID- 7987612 TI - Effects of the antimycotic molecule Iturin A2, secreted by Bacillus subtilis strain M51, on arbuscular mycorrhizal fungi. AB - A new system, devised for the study of early stages of arbuscular mycorrhizal infection, was used to test the effect of the biological control agent Iturin A2, secreted by the strain M51 of Bacillus subtilis, on the development of arbuscular mycorrhizal fungi. The saprophytic growth of the fungus Glomus mosseae was inhibited by Iturin A2 concentrations higher than 100 micrograms/g of sand; whereas, in the presence of the tomato host plant, both, pre-infection events and intraradical growth were not negatively influenced by the antifungal compound; furthermore, the development of arbuscular mycorrhizal symbiosis was not impeded by the biocontrol agent in field conditions, while Fusarium oxysporum f. sp. lycopersici infection was hindered. PMID- 7987613 TI - The effect of some antibiotics on Enterococcus faecium SF 68 inoculated in germ free mice. AB - A strain of Enterococcus faecium SF 68 (sensitive to penicillin, tetracycline, virginiamicin and tylosin, but resistant to streptomycin) was administered to five groups of germ-free mice. Each group was subsequently given 40 micrograms/ml and then 80 micrograms/ml of a single antibiotic. The following determinations were made: a) colonization of the bacterial strain before and after administration of the antibiotic and b) the MICs in the original strain and after administration of the antibiotic (80 micrograms Iml). The results show that in the mice treated with streptomycin, colonization is not influenced by the antibiotic treatment; in mice treated with antibiotics to which the strain is sensitive, the colonization increases in proportion to the level of the antibiotic resistance (tylosin and tetracycline). PMID- 7987614 TI - Comparison of L-aspartate 4-carboxy-lyases of Cunninghamella elegans and Penicillium citrinum. AB - L-Aspartate 4-carboxy-lyase of Cunninghamella elegans and Penicillium citrinum has a pH optimum of 5.5. Maximal activity of both enzymes is obtained at 40 degrees C, and both are thermolabile. The Km of the C. elegans enzyme for L aspartate is 25 mM, while that of the P. citrinum enzyme is 27 mM. The two enzymes are specific for L-aspartate. They are activated by pyridoxal 5-phosphate and a number of alpha-keto acids. The catalytic activity of both enzymes is stimulated by Co2+, Fe2+, Ni2+ and Mn2+ ions and inhibited by Zn2+ and Cu2+. Inhibition by iodoacetate and activation by SH-compounds suggest that sulfhydryl groups may participate in enzyme activity. PMID- 7987615 TI - Mycotoxin producing potential of some isolates of Aspergillus flavus and Eurotium groups from meat products. AB - All strains (92) of A. flavus group proved to be positive for production of aflatoxin (45 to 1200 micrograms/50 ml medium) on potato dextrose liquid medium, while 59 strains only proved to be positive (35-310 micrograms/50 ml) on 15% NaCl potato-dextrose liquid medium. Most of the strains tested of A. flavus, A. flavus var. columnaris and A. oryzae produced aflatoxins B1, B2, G1 & G2. All positive strains of A. tamarii produced aflatoxins G1 & G2 while the tested isolate of A. zonatus produced aflatoxins B1 & G1. Of 95 strains tested of Eurotium, aflatoxins B1 & G1 were produced by one strain of each of E. chevalieri var. intermedium, E. repens and E. rubrum. Gliotoxin was detected in the extract of two strains of E. chevalieri and one strain of each of E. chevalieri var. intermedium and E. pseudoglaucum on the salt-free medium, and two strains of each of E. chevalieri, E. chevalieri var. intermedium and one of E. pseudoglaucum on 15% NaCl medium. Sterigmatocystin was produced by some strains of E. chevalieri, E. chevalieri var. intermedium, E. amstelodami, E. pseudoglaucum and E. rubrum on the two experimental media. One strain only of E. repens produced ochratoxin A while citrinin was detected in the extract of one strain of E. pseudoglaucum. PMID- 7987616 TI - Photodynamic therapy in gastroenterology. AB - Photodynamic therapy is a new endoscopic procedure for the treatment of malignant or premalignant structure lesions. The underlying principle is selective destruction of tumor cells, which, after accumulating a so called photosensitizer, are irradiated with light of a particular wavelength. Clinical experience to date suggests that, in the field of gastroenterology, endoscopically accessible tumors located within the esophagus, the stomach, or the colorectum of patients with a high surgical risk are particularly suitable for such treatment. If such tumors are limited in size, they can often be treated with curative intent, and remission rates better than 90% can be achieved. Also, palliatively, the tumor mass can be reduced appreciably in a large percentage of patients. The main side effect of this treatment is photosensitization of the skin; perforations and hemorrhage are rare. Improvements in technology and photosensitizers suggest that the procedure will become an established part of the therapeutic concept for gastrointestinal diseases. PMID- 7987617 TI - Endoscopic evaluation of Barrett's esophagus. AB - Barrett's esophagus is a premalignant condition, the recognition of which is increasing because of widespread utilization of upper endoscopy. Awareness and identification of the squamocolumnar junction are key to endoscopic recognition of Barrett's esophagus. Biopsy is essential to document Barrett's esophagus and to detect dysplasia. Specific mucosal abnormalities need to be targeted. In addition, systematic biopsies need to be taken for dysplasia/carcinoma surveillance. Experimental endoscopic application of energy to Barrett's esophagus offers the potential for elimination of this lesion. Endoscopic recognition and diagnosis remain the key to clinical management of Barrett's esophagus. PMID- 7987618 TI - Esophageal infections: etiology, diagnosis, and management. AB - With the advent of transplantation and the acquired immunodeficiency syndrome (AIDS), esophageal infections are now a common medical problem. The most common infections involving immunocompromised nonhuman immunodeficiency virus (HIV) infected patients include viral disease (herpes simplex virus and cytomegalovirus) and Candida. In HIV-infected patients, Candida esophagitis is by far the most common infection; viral disease is seen less frequently. In contrast to other immunocompromised patients, these patients may have esophageal disease from a variety of other fungi and viruses. Immunocompromised patients in whom esophageal symptoms develop after transplantation usually undergo endoscopy for diagnosis because of the possibility that alterations in immunosuppressive agents will be required if an opportunistic infection is causative. In contrast, HIV infected patients with new-onset esophageal symptoms are usually treated empirically with oral systemic antifungal therapy given the prevalence of Candida esophagitis. Barium esophagography may, however, be worthwhile, depending on the clinical setting, such as the possibility of a reflux-induced stricture. In HIV infected patients, radiography is less often utilized in the setting of a low CD4 lymphocyte count given the likelihood of an opportunistic infection that requires endoscopic biopsy for a definitive diagnosis. Oral systemic antifungal therapy with either ketoconazole or fluconazole is very effective for the treatment of Candida esophagitis, and these agents have also shown efficacy in the prophylaxis of fungal infections following transplantation, as well as in patients with AIDS following oropharyngeal and esophageal candidiasis. Antiviral therapy with acyclovir for herpes simplex virus and ganciclovir and foscarnet for cytomegalovirus are effective. The efficacy rate for these antiviral agents appears similar in all immunocompromised patients. These agents have also been utilized prophylactically following transplantation. In summary, a variety of infections may involve the esophagus in immunocompromised patients. The diagnostic strategies utilized in these patients are similar; endoscopy and biopsy are the most cost-effective strategy given the need for mucosal biopsy for a definitive diagnosis. Importantly, efficacious therapy is available to treat these disorders. Nevertheless, in patients with AIDS, identification of an opportunistic esophageal disease portends a poor prognosis. PMID- 7987619 TI - Nonsteroidal antiinflammatory drugs and the gastrointestinal tract. AB - Nonsteroidal antiinflammatory drugs (NSAIDs) are used in large amounts for analgesic, antiinflammatory, and antithrombotic indications. This use is not without side effects on the gut and other organs, and some of these side effects may be serious and even lethal. No NSAID has been shown to be without side-effect potential. Use increases with age, and age poses additional risks to patients with side effects. The most serious side effects are perforation of peptic and gut ulcers and gastrointestinal (GI) bleeding, which NSAIDs, and especially acetylsalicylic acid (ASA; aspirin), may promote from both ulcer and nonulcer lesions of both the upper and lower GI tract (i.e., both acid- and nonacid dependent). Upper GI mucosal lesions range from trivial--petechiae and superficial erosions--to significant and potentially serious deep (chronic) peptic ulcers, esophagitis, and, less commonly, small and large gut ulcers. Symptoms may occur independently of observable lesions, and serious lesions may occur without any prior symptoms. The risk of ulceration due to therapeutic doses of NSAIDs is estimated at 5- to 10-fold. NSAIDs also delay healing of conventional peptic ulcers. Moreover, ASA abuse, often surreptitious and discoverable by serum salicylate level measurement, may cause totally intractable gastric or duodenal ulceration. Surgery is contraindicated because relapse is inevitable and progressively more serious. The rational use of NSAIDs is discussed, and prophylactic and treatment strategies are proposed. None seems entirely satisfactory, and the best prophylaxis would be to avoid the use of NSAIDs except for proven indications. Until the mechanisms whereby NSAIDs both cause injury and provide therapeutic benefits can be separated, the problem of side effects and their prevention or treatment remains unresolvable. PMID- 7987620 TI - Diagnostic tests in chronic pancreatitis. AB - We review the values of various tests in the diagnosis of suspected chronic pancreatitis, and we give a practical approach to diagnosis. Most cases can be diagnosed by a consideration of history, simple radiology, and serum enzymes. Problems arise in patients with noncalcific early chronic pancreatitis, in whom pain alone is the main feature. In these patients, a sequence of tests may be required to arrive at a diagnosis of probable or possible pancreatitis to one that is proven. In some cases, only time will tell. PMID- 7987621 TI - Acute colonic pseudo-obstruction (Ogilvie's syndrome). AB - Acute colonic dilation without mechanical obstruction (Ogilvie's syndrome) was first described in 1948. The pathogenesis remains unknown but likely involves imbalance between sympathetic and parasympathetic colonic innervation. Patients are generally hospitalized with another serious illness when the syndrome develops. There are no controlled data on the efficacy of any therapy. A trial of conservative measures alone is appropriate in a subset of patients who lack significant abdominal pain, peritoneal findings, and who have one or more potential underlying factors that are reversible. Colonoscopy is the initial invasive therapeutic maneuver but fails in 31% of patients and is followed by recurrence in 40% of those in whom initial decompression is successful. Placement of a tube during colonoscopy may help to prevent recurrence. No pharmacological therapy is proven effective, although anecdotal successes with some agents suggest clinical trials that should be performed. A minority of patients still require surgical cecostomy, which has been recently performed via laparoscopy. PMID- 7987622 TI - Immunosuppressive drugs in Crohn's disease. AB - We review clinical experience with the immunosuppressive drugs 6-mercaptopurine (6-MP) and azathioprine, cyclosporine, and methotrexate in the management of patients with Crohn's disease. 6-MP and azathioprine are closely related structurally. Their exact mechanism of action is unknown, but both cause immunosuppression by interfering with nucleic acid metabolism in the immunological sequence that follows antigenic stimulation. 6-MP and azathioprine have proved most useful for two indications: reducing steroid requirements and healing fistulas. Among patients who are dependent on steroids for control of active inflammatory Crohn's disease, approximately 50% can be completely weaned from prednisone, and an additional 25% can tolerate a substantial dose reduction when treated with 6-MP or azathioprine. Likewise, 6-MP is effective in closing fistulas in approximately one third of patients and in reducing fistula drainage in an additional one third. However, the onset of action is slow and the results may be dose dependent. Cyclosporine, a selective immunosuppressant drug, inhibits T lymphocytes by inhibiting expression of interleukin-2 and its receptors. Its principal usefulness may be in patients with disabling fistulas or active steroid refractory colitis who cannot tolerate the several months required for a remission induced by 6-MP or azathioprine. Methotrexate, a dihydrofolate reductase inhibitor, has antimetabolite and antiinflammatory properties. Methotrexate is only slightly, if at all, faster acting than 6-MP or azathioprine. Its principal usefulness may therefore be in cases when these other drugs have not been tolerated or are ineffective.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7987623 TI - Hepatic sarcoidosis presenting as acute abdominal pain. PMID- 7987624 TI - Cutting artefacts on ultrathin cryosections of biological bulk specimens. AB - Cryoelectron microscopy of ultrathin cyrosections permits study of the ultrastructure of cells in the hydrated state. However, cryosectioning deforms the cut volume as the sections are compressed in the cutting direction while their thickness is increased with respect to the cutting feed. The compression has been measured on the elliptical deformation of lipid droplets in liver cells. It is about 40% at 48 degrees cutting angle while it is reduced to 30% at 38 degrees. The section deformation involves the underlying ultrastructure as far as the specimen is deformable. Three deformation modes are discussed. Crystalline ice is broken into chips which are tilted and pressed out of the section plane to account for the section deformation. Within one chip, the ultrastructure of the ice is preserved. In contrast, hydrated catalase crystals deform plastically. Cutting shortens the crystal distances the same amount as cryosections are compressed. Distances in hexagonal DNA crystals are also influenced by cutting since the spots of diffraction patterns are blurred in the cutting direction. However, the crystal spacing is not shortened in the cutting direction. The crystal apparently reorganizes during cutting deformation. PMID- 7987625 TI - Possibilities and limitations of cytochemical methods in diagnosis of acute leukemia. AB - Accurate identification and classification of leukemic blast cells is a very important prerequisite of the precise diagnosis of acute leukemia and has a great impact on therapy and prognosis. The purpose of this review is to consider, in the broad sense of the word, the present possibilities and limitations of enzyme cytochemistry and to emphasize how cytochemistry may contribute, on integration with the other methods of study, to the final classification and differential diagnosis of acute leukemia, a highly variable hematological disorder. In this review, the role of conventional enzyme cytochemistry, either dominant or subsidiary, in the discrimination of acute leukemia subtypes is discussed. The survey confirms the absolute necessity of immunologic marker analysis in the accurate diagnosis of acute lymphoblastic leukemia, undifferentiated or minimally differentiated leukemia and mixed-lineage leukemia because in these cases, the cytochemical evaluation provides insufficiently relevant information regarding blast cell origin, specificity of leukemia subtypes and the discrete stages of leukemic cell maturation. On the other hand, cytochemical investigation is appreciated to be dominant over immunophenotyping in characterizing acute myeloid leukemia, because of the lack of specificity of the majority of immunological markers against myeloid antigens and, because of the availability of standardized and sufficiently specific cytochemical reactions. The cytogenetic, molecular biological and electron microscopic studies mentioned in this review supplement the important information for correct differential diagnosis of acute leukemia. The prognostic impact of enzyme cytochemistry in correlation to other methods is evaluated. PMID- 7987626 TI - Cytochemistry and immunocytochemistry of nucleolar chromatin in plants. AB - This review attempts to document the most relevant data currently available on the in situ localization of nucleolar chromatin on plant cells. The data provided by the most powerful and recent in situ techniques, such as DNA specific ultrastructural staining, immunogold labelling, in situ molecular cytochemistry, in situ hybridization or confocal microscopy, are summarized and discussed in the light of the potential and limitations of each individual methodology. The presence of DNA in both fibrillar centres and regions of the dense fibrillar component is extensively documented. Data on the nucleolar distribution of other important macromolecules involved in ribosomal transcription are also shown and referred to with regard to the location of DNA. The comparison with the available data on the animal cell nucleolus points towards models of similar functional organization in both plant and animal nucleoli. PMID- 7987627 TI - Recent developments in medical applications of SIMS microscopy. AB - The purpose of this review is to present the recent developments in the medical applications of SIMS microscopy. This technique is one of the microanalytical mass spectrometry methods which allow in theory the detection of all the elements of the Mendeleiev table as well as the separation of stable and radioactive isotopes. It is based on a phenomenon whereby a biological sample surface is sputtered by bombardment with an energetic 'primary ion' beam. Part of the sputtered matter is ionized and the resulting 'secondary ions' are characteristic of the atomic composition of the analyzed area. These secondary positive or negative ions are collected and separated in a mass spectrometer at low or high mass resolution, which is dependent on both the element studied and its concentration. An analytic image which conserves the tissue distribution of the selected element is displayed on a fluorescent screen linked to an image processing system. Local elemental concentration can also be measured. Results are highly dependent on the techniques used for sample preparation which should preserve both the chemical and the structural integrity of the tissue. Further, the ionic images must be correlated with corresponding images of the same areas of the serial sections observed in a photonic microscope. With our SIMS microscope (lateral resolution approximately 0.5 microns, and mass resolution 300 to 12,000) we have demonstrated that this microscopic imaging technique is suitable for physiopathological studies. We revisited thyroid iodine metabolism by mapping chemical elements such as 32S and 127I, characteristic of hormonal physiology. Newly organified iodine (radioiodine) can be evaluated in relation to previously stored iodine (127I) in a given follicle, thus allowing an appraisal of glandular adaptation to aging and iodine overload. Another area in which SIMS can be used in medicine, is for the localization of drug markers in tumor tissue (e.g. fluorine-5-fluouracil, iodine in iododeoxyrubicin). This could facilitate the evaluation of the intratumor drug concentration at the onset of the treatment. Likewise, SIMS can be used to localize radiopharmaceuticals used in diagnosis (e.g. technetium) and therapy (131I of metaiodobenzylguanidine). This would permit a better evaluation of the radiation dose delivered to tissue. Further prospects are within reach with the imminent advent of higher lateral resolution (0.05 microns) SIMS microscopes. PMID- 7987628 TI - Cervical lymphadenitis in infants and children. AB - One of the more common cervical lesions seen in children is cervical lymphadenitis. Pediatricians handle the vast majority of these children who present with an acute infection. The pediatric surgeon becomes involved only when the presumptive infection does not respond to antibiotic therapy, or if the lump becomes chronic and persists for weeks or months. In this situation the specter of malignancy looms, but benign causes still predominate. The infectious agents range from common bacteria such as staphylococci and hematologic staphylococci to atypical mycobacterium, fungi, and other much less common organisms. A broad discussion of the numerous causes of cervical lymphadenitis is presented together with a pragmatic diagnostic and therapeutic approach. PMID- 7987629 TI - Thyroglossal duct cysts and branchial cleft anomalies. AB - Thyroglossal duct cysts and branchial cleft anomalies are important in the differential diagnosis of cervical lesions. Both lesions are common and are seen more commonly in the child than in the adult. Considerable discomfort and morbidity may be associated with severe infections occurring in both of these lesions. Of importance is the observation that once these congenital cysts become infected, subsequent surgical removal is very difficult, and recurrence may result. For these reasons it is essential that the clinician become familiar with the embryology of these lesions, which is vital to the understanding of them. In addition, the development of skills in diagnosing and managing this condition is essential. PMID- 7987630 TI - Hemangiomas, cystic hygromas, and teratomas of the head and neck. AB - Hemangiomas, cystic hygromas, and teratomas are the most common bulky lesions presenting in the head and neck of infants, but cystic hygromas and teratomas are rare, and most hemangiomas are initially small. Historically, hemangiomas have been watched with the belief that they all involute with good results. Recognition that this is often not the case, and newer more successful and less complicated treatment modalities are changing this approach, albeit slowly. Maternal fetal sonography, in addition to showing that most cystic hygromas are associated with fetal anomalies and fetal demise, has facilitated careful planning and improved outcomes for infants born with isolated cystic hygromas and teratomas. PMID- 7987631 TI - Head and neck malformations of the pediatric airway. AB - The authors describe the head and neck malformations that can affect the upper aerodigestive tract. The article is organized so that it begins with the nose and extends through the larynx. A diagnostic table for the localization for an airway lesion is given. Medical and surgical treatment regarding various malformations including choanal atresia, Pierre Robin sequence, laryngomalacia, laryngeal edema, and subglottic stenosis are discussed. PMID- 7987632 TI - Pediatric surgical pathology of the head and neck. AB - Anatomically, the head and neck region is composed of a greater variety of structures than any other part of the body. Practically all the anatomic structures can be the site of the various pathological processes. Multiplying the anatomic structures by the various pathological processes produces an infinite number of pathological diagnoses that may be encountered in the head and neck region. The large number of pathological possibilities provides a challenge for the pathologist working in surgical pathology of the head and neck region in children. Whenever a specimen is submitted to the laboratory, it is necessary to have at one's disposal a list of differential diagnoses. Clinical information is of importance in interpreting specimens if excellence in patient management is to be achieved. Therefore, it is imperative that open communication exist between the clinician and the pathologist. Thus, a combination of knowledge of the pathological possibilities, the range of differential diagnoses, the ability to use newer technologies, such as cell marker determinations by flow cytometry and immunoperoxidase, and dialogue with clinical physicians will provide some assurance of the ultimate in patient care. Herein the authors discuss some of the more common and important neoplasms encountered in pediatric head and neck surgical pathology. PMID- 7987633 TI - Papillary carcinoma of the thyroid in children. AB - Papillary carcinoma of the thyroid is the most common thyroid cancer in children. It usually occurs in the teenage female and presents as a 3-cm mass within the thyroid itself. Although the tumor is well differentiated, almost 80% of all children will present with local lymph node metastasis. Despite this metastasis, most children have a life expectancy that parallels those of their peers for 30 years. Treatment for well-differentiated papillary carcinoma includes surgical excision of all cancerous tissue and removal of the affected lymph nodes. Radioablation of residual disease has been effective. PMID- 7987634 TI - Medullary thyroid carcinoma in children. AB - Medullary cancer of the thyroid (MCT) in children, although uncommon, represents not only a most intriguing problem but also one that is a model of early cancer detection that results in cure. MCT in children is usually a part of the multiple endocrine neoplasia (MEN) syndrome (MCT, pheochromocytoma, and hyperparathyroidism) and is detected by screening studies. MCT arises from C cells that secrete calcitonin, with C-cell hyperplasia representing the precancerous state. Both are diagnosed by measuring calcitonin levels both basally and after stimulation with pentagastrin. Screening studies should begin shortly after birth in infants at risk for MEN IIb and by age 1 year in children at risk for MEN IIa. Application of this approach should result in near elimination of the spread of cancer in children with MCT. PMID- 7987635 TI - Head and neck neuroblastoma. AB - Primary neuroblastoma of the head and neck is rare. The clinical presentation and physical findings are related to the child's age, the stage and location of the primary tumor, and its attendant biological behavior. The differential diagnosis is varied, and initial evaluation includes a thorough physical examination, selected laboratory studies, and specific high-yield imaging techniques. The prognosis of these lesions has been increasingly favorable, even when the disease is not localized. Carefully planned surgical approaches provide local control, and radiation and chemotherapy may be beneficial in more extensive tumors. Second malignancies occur after treatment, and long-term follow-up is necessary. PMID- 7987636 TI - Head and neck rhabdomyosarcoma. AB - Rhabdomyosarcoma (RMS) accounts for approximately half of all pediatric soft tissue sarcomas and 15% of all pediatric solid tumors. The head and neck site accounts for 35% of all RMS. The head and neck site can be divided into three broad groups: cranial paramengingeal, orbital, and nonorbital-nonparameningeal. The predominant specific sites are orbit and nasopharynx, each accounting for 25%, with paranasal sinuses, ear, intraoral, neck, and parotid each accounting for about 10%. RMS in the orbit has the best outlook; parameningeal involvement is associated with the poorest outcome. Treatment is determined by the extent of disease, ease of resectability, and precise site. Superficially placed tumors can be managed either with excision and relatively nontoxic adjuvant chemotherapy or by biopsy, radiation, and similar chemotherapy, with equally good results (survival rate, 90%). More deeply placed lesions, especially those with parameningeal locations or extension, generally are not removable and require radiation therapy, including radiation to the entire cranial neuraxis, intrathecal chemotherapy, and very aggressive chemotherapy. The more intensified therapy resulted in increased survival rates of 57%. Non-RMS soft tissue sarcomas occur infrequently in the head and neck. Resection is the most effective treatment for this diverse group of tumors. Wide resection is best, if feasible. The role of chemotherapy is unclear because most of these tumors are radiosensitive. These tumors are often managed by protocols used for the treatment of RMS or extraosseous Ewing's sarcoma. PMID- 7987637 TI - Non-Hodgkin's lymphoma of the head and neck in childhood. AB - Non-Hodgkin's lymphomas (NHL) in childhood account for approximately 10% of solid tumors reported for this age group, and almost 10% of all these lymphomas arise in the head and neck. Most head and neck NHL is a B-cell phenotype (70%) and is characterized by diffuse involvement of anatomic structures. Analysis of the cell surface expression of specific molecules of interest, including immunoglobulins, T-cell receptor components, and antigens specific for immunoblastic cells at discrete points in ontogenic development, has resulted in a greater understanding of the origins and biological behavior of childhood lymphomas. This has significance for the surgeon because specialized studies including immunophenotyping, cytogenetics, and Southern analysis require adequate amounts of tissue that has been properly processed after removal from the patient. In addition, because chemotherapy is the mainstay of lymphoma treatment, the surgical oncologist must avoid the postoperative morbidity inherent in en-bloc resection of other malignancies of the head and neck and thereby facilitate initiation of therapy. This article discusses the clinical presentation, imaging, treatment, and outcome of NHL primary in the head and neck region. Individual characteristics peculiar to specific anatomic sites are reviewed. PMID- 7987638 TI - Cancer genetics. AB - The fundamental ideas on the causes of cancer have been known for some time. They can now be interpreted in terms of the notion that cancer is essentially a genetic disease at the cellular level. The aim of this introductory article is to provide a brief overview of these ideas and the evidence for them, as well as some of the implications for future approaches to the prevention, early detection and treatment of cancer. PMID- 7987639 TI - The inherited component of cancer. AB - All cancer types exhibit familial clustering, suggestive of a significant inherited component; however, to date only a few of the genes responsible have been identified and the inherited component, if any, underlying most common cancers has not been well defined. Amongst the important known susceptibility genes are those dominant genes conferring a high risk of breast and ovarian cancer (BRCA1), colon cancer (hMSH2 and hMLH1), and melanoma (MLM). All these genes confer a high lifetime risk of the disease concerned, but are rare and only account for a small minority (less than 5%) of cases. However, there are also commoner genes conferring lower risks but accounting for a more substantial fraction of cancer cases; those so far identified include the ataxia telangiectasia gene and the HRAS1 minisatellite locus. PMID- 7987640 TI - Identification and characterisation of cancer genes. AB - Cancer genes have been subdivided into oncogenes and tumour suppressors though the distinction is not entirely valid. In many cases their effects can be demonstrated by induction or reversal of a transformed phenotype following transfection into a suitable host cell but full characterisation requires isolation by positional cloning and analysis of function at the molecular level. Almost all have been ascribed some function within the complex pathways of signal generation, receipt and response that regulate cell growth and differentiation. However, few, if any, tumours result from just a single mutation and the key to a real understanding of the molecular basis of malignancy must be studies, currently in their infancy, of interactions between the various genes implicated in the initiation and progression of cancer. PMID- 7987641 TI - Viruses and human cancer. AB - Epstein-Barr virus (EBV), hepatitis B virus (HBV), HTLV-I and some human papillomaviruses (HPVs) appear to contribute to the development of a large proportion of certain human cancers. Although the epidemiological evidence linking infection with these viruses to malignancies is generally convincing, only for the HPVs have experimental systems indicated a clear role for some of the HPV encoded genes in tumour cell growth. In these cases, molecular analysis is revealing the mechanisms by which the virally encoded oncogenes function to perturb the normal regulation of cell growth. For HTLV-I, EBV and HBV the mechanism by which the viruses contribute to tumour cell growth is obscure, even though much has been learned about cell transformation in culture by these viruses. A detailed understanding of the mechanism of oncogenesis will be required to design therapeutic drugs for the treatment of these cancers. Prophylactic vaccination resulting in prevention of infection may be an effective approach to reduce the incidence of some of these common cancers. PMID- 7987642 TI - p53 and human cancers. AB - Mutations in the p53 gene are one of the commonest specific genetic changes found in human cancer. The p53 gene is not required for normal development but lack of p53 function confers an enormously elevated risk of developing cancer, thus it seems truly to act as a tumour suppressor gene. The p53 protein is normally present in minute amounts in cells but when cells are exposed to genotoxic stimuli p53 levels rise rapidly and initiate a programme of cell death, probably by means of transcriptional regulation. This response is lost in many tumour cells as they have either inactivated their p53 genes by mutation or blocked the activity of p53 through the production of proteins that bind to it and neutralise it. Mutant p53 proteins accumulate to high levels in many cancer cells and the p53 protein and the p53 response to DNA damage represent key points for therapeutic intervention. PMID- 7987643 TI - Genetics of paediatric solid tumours. AB - The average child in the UK stands a 1:600 chance of developing a malignancy by the time they are 16 years of age, which compares with the 1 in 5 adults who die of cancer. The tumours children develop are very different from those seen in adult life. Histologically they resemble their relatively undifferentiated, fetal counterparts rather than the fully differentiated structures seen at, or soon after birth. The genetic events responsible for initiating children's tumours, therefore, must occur during embryonic life and prevent normal differentiation. These cells are frozen in the undifferentiated state and the malignant phenotype eventually arises as a result of secondary changes. The acquisition of secondary events occurs at varying rates and accounts for the variation in the time of presentation of the tumour. Unlike the adult situation environmental factors have not been identified as common causes of genetic damage in children's tumours. PMID- 7987644 TI - Familial cancer syndromes and clusters. AB - The study of rare families in which a variety of cancers occur, usually at an early age and with patterns consistent with a common hereditary mechanism, has contributed much to our understanding of the process of carcinogenesis. So far, genes identified as having a role in cancer predisposition in these families have also been important in the histogenesis of sporadic cancers. In the two most clearly defined cancer family syndromes, the Li-Fraumeni syndrome and Lynch syndrome II, the genes involved predispose to diverse but specific constellations of cancers. Genes associated with site-specific familial cancer clusters may also give rise to increased susceptibility to other cancers, and site-specific clusters may represent one end of a spectrum. A consistent feature of familial cancer syndromes is the variable expression within and between families. A challenge for the future will be to determine other factors which may interact with the principal genes involved, giving rise to this variability. PMID- 7987645 TI - Genetics of colorectal cancer. AB - Recent advances in understanding the genetic basis of malignant disease have been dominated by research in colorectal cancer. In familial adenomatous polyposis, characterisation of the causative gene had immediate clinical relevance allowing confident prediction of disease inheritance. Somatic mutations in this gene have been demonstrated to have a fundamental role in the development of sporadic colorectal cancer. More recently, efforts have focused on the genetic abnormalities responsible for hereditary non-polyposis colorectal cancer which may possibly account for up to 15% of all colorectal malignancies. In the foreseeable future, it is possible that significant population-based genetic screening for this condition will be available. As the molecular basis of colorectal cancer is elucidated, it will inevitably lead to radical changes in clinical management, particularly with the possible introduction of gene therapy and chemoprevention. This review discusses the current developments in colorectal cancer genetics which will be central to such changes. PMID- 7987646 TI - Genetics of breast and ovarian cancer. AB - Studies of familial breast and ovarian cancer have traditionally been directed towards a single type of cancer, but recent evidence leads us to consider these two types of cancer together. The original evidence for a common hereditary basis for breast and ovarian cancer comes from the observation of large families with several cases of both types. The number of cancers in these families was too great to be explained by chance and none of the known environmental risk factors are sufficient to account for the clustering. Statistical analysis performed on a number of breast-ovary cancer families identified by Dr Henry Lynch and his colleagues led them to conclude that the clustering could be explained by the effect of a single dominant gene. Women with breast cancer are at increased risk of developing a second primary cancer of the ovary; and relatives of women with breast or ovarian cancer are at roughly double the risk for either tumour. The most convincing evidence, however, for a common predisposition for breast and ovarian cancer comes from genetic linkage studies. In a linkage study cancer susceptibility in a family is shown to be transmitted with a particular allele of genetic marker of known chromosomal location. A gene from chromosome region 17q12 q21, designated BRCA1, identified in 1990 by Dr Mary-Claire King and colleagues, predisposes to both cancer of the breast and the ovary. PMID- 7987647 TI - Genetics of melanoma. AB - Melanoma may cluster in families with 'family cancer syndromes' in which there is a predisposition to a variety of different tumours. Other families seem vulnerable to melanoma alone. In the majority of these families, the propensity to melanoma is associated with the presence of abnormal melanocytic naevi, the so called atypical mole syndrome (AMS) phenotype. However, in a smaller number of families, individuals are susceptible to melanoma but have normal naevi. There appears, therefore, to be clinical (and probably genetic) heterogeneity. Segregation analysis does not support a predisposition by single dominant gene as an explanation for the AMS/melanoma syndrome. To date, a single gene which is clearly important for susceptibility to melanoma has not been identified. Karyotypic studies of melanoma tumours have pointed to chromosomes 1, 6, 7, 9 and 10 as possible sites for melanoma related genes. Loss of heterozygosity studies have suggested that chromosome 9 may carry a tumour suppressor gene important in familial disease, and linkage studies appear to confirm this. It is not yet clear, however, what percentage of familial melanoma is attributable to this gene. A more longstanding suggestion that a gene on chromosome 1 may be important has not been confirmed, but a chromosome/gene may be responsible for susceptibility in a small subset of melanoma families. Even within AMS families, there is a lack of concordance between the AMS phenotype and susceptibility to melanoma. This might be explained either by the effects of modifying genes, or the environment. PMID- 7987648 TI - Genetic changes in the development of lung cancer. AB - Both inherited predisposition and acquired somatic genetic changes contribute to lung tumour development but the former is likely to be the minor component. The relative ease with which lung tumours can be established as cell lines has resulted in extensive cytogenetic analysis, and, this together with molecular techniques which assess loss of genetic material has revealed consistent patterns of genetic damage. Some of these characteristic somatic genetic changes have been traced back to the pre-invasive stage of tumour development and this information may contribute to the future management of this currently intractable disease. PMID- 7987649 TI - Genetics of urological cancers. AB - Investigations into inherited susceptibility to urological cancers have provided new insights into the clinical and molecular genetics of urological neoplasia. This review focuses on current knowledge of the genetics of renal, bladder, prostate and testicular neoplasia. Recent advances include (i) the isolation of the von Hippel-Lindau disease gene which is involved in the pathogenesis of familial and nonfamilial renal cancer, (ii) elucidation of the mechanism of multicentricity in bladder cancer, (iii) evidence that a significant proportion of early onset prostate cancer may be attributable to dominantly inherited susceptibility gene (or genes), and (iv) identification of specific cytogenetic and molecular events in the pathogenesis of testicular germ cell tumours. PMID- 7987651 TI - Metabolic polymorphisms in carcinogen metabolising enzymes and cancer susceptibility. AB - Molecular genetic analysis is providing us with enormous advances in understanding the pathogenesis of human diseases such as cancer. The study of familial disease and the subsequent mapping and identification of the mutations which contribute to disease susceptibility, is not only providing insights into the factors involved in the pathogenesis of the disease but also identifying new targets for therapy. It is now clear that human tumours result from a complex sequence of mutation events. Each individual step makes the mutated cell more independent of its normal growth regulatory processes, eventually resulting in the formation of a metastatic tumour. There are a multitude of biochemical changes that these mutations confer, which provide preneoplastic cells with a selection advantage. In addition to an increased rate of cell division, such changes may make the cells resistant to cytotoxic insult or to programmed cell death. They can also confer an increased ability to survive independent of a normal hormonal environment. It is now clear that all these types of change may contribute to tumour cell progression. PMID- 7987650 TI - Cancer and DNA processing disorders. AB - Defects in cloned DNA repair genes are now associated with particular human disorders in which an important feature is a predisposition to cancer. Recently some repair genes have been implicated in other aspects of DNA metabolism such as transcription initiation. In addition mutations in a single gene can give rise to phenotypes recognised clinically as different disorders. These newly appreciated complexities, amongst others, will eventually help us to understand the development of the complete clinical phenotype in a range of 'DNA processing disorders'. PMID- 7987652 TI - Setting up and running a familial cancer clinic. AB - This article is based on the author's own experience of establishing and running a familial cancer clinic over the past 9 years. There are certainly other ways of doing it, depending on the clinical context--resources, involvement of colleagues from other specialities--and each clinic should be adapted to local circumstances. As the familial component of the common cancers such as breast and colorectal cancers is increasingly recognised, and DNA-based predictive testing becomes a possibility, the future demand for genetic advice is likely to increase dramatically. This will almost certainly require a re-appraisal of the way in which familial cancer services are provided, which is discussed in the final section. PMID- 7987653 TI - Transfusion-related hepatitis. PMID- 7987654 TI - Primary hyperoxaluria type I. PMID- 7987655 TI - Evidence of oxidant injury and tubular damage in early diabetic nephropathy. AB - Two groups of patients with insulin-dependent diabetes mellitus of > 10 years duration and either persistent normoalbuminuria (group 1, n = 49; albumin excretion < 30 mg/day) or microalbuminuria (group 2, n = 33; albumin excretion 30 300 mg/day) were investigated for evidence of free oxygen radical activity (erythrocytic superoxide dismutase and glutathione peroxidase) and oxidant injury (serum malondialdehyde). Glomerular proteinuria (albuminuria, transferrinuria), tubular proteinuria (retinol-binding protein) and tubular enzymuria (N-acetyl glucosaminidase and leucine aminopeptidase) were also measured. Healthy controls (n = 38) were matched for age and sex. Groups 1 and 2 were similar in terms of age, sex, duration of diabetes and recent glycaemic control. Serum cholesterol and creatinine were similar in all three groups. Free-radical activity and oxidant injury were significantly higher in groups 1 and 2 than in controls (p < 0.001). Glomerular proteinuria, tubular proteinuria and enzymuria were significantly higher in group 2 than in group 1 and controls (p < 0.01). Group 1 had significantly higher transferrinuria, tubular enzymuria and tubular proteinuria than controls. However, groups 1 and 2 were similar in degree of free oxygen radical generation and oxidant injury. In diabetic nephropathy, oxidant injury and renal tubular damage accompany and may even precede microalbuminuria. The presence of these abnormalities in the absence of glomerular proteinuria favours the hypothesis that alterations first occur in the peritubular microcirculation, which by causing oxidant injury and tubular damage, may initiate diabetic nephropathy. PMID- 7987656 TI - C3 nephritic factor and SLE: report of four cases and review of the literature. AB - We present four patients with C3 nephritic factor associated with partial lipodystrophy and/or mesangiocapillary glomerulonephritis type II. Each of these patients subsequently developed features of SLE, with an onset between 2 and 24 years after the development of the lipodystrophy or glomerulonephritis. All four patients had antinuclear antibodies and three of the four had anti-Ro antibodies. These patients bring to six the number of reported cases of this association. Possible explanations for the link between these two conditions are discussed. PMID- 7987657 TI - Factors determining the long-term outcome of surgery for acromegaly. AB - Seventy-nine patients with acromegaly were investigated before and after transsphenoidal adenomectomy, to determine the immediate and late outcome, the pre-operative features associated with a good result, and the accuracy of post operative testing in predicting outcome. Pre-operative evaluation included basal growth hormone (GH), GH response to oral glucose tolerance test (OGTT), GH response to thyrotrophin-releasing hormone (TRH), tests of pituitary reserve, and pituitary scanning to assess tumour size. A few weeks after surgery, these tests were repeated. The patients were recalled for late assessment 1-13 years (median 86 months) after the operation. At the immediate postoperative testing, minimum GH after oral glucose was < or = 2 mU/l in 48.7%, < 5 mU/l in 76.3% and < 10 mU/l in 84.2%. Only 12 patients had GH > 10 mU/l. Basal GH was < or = 2 mU/l in 21%, < 5 in 59.2%, < 10 in 73.6% and < 20 in 90.8%. A minimum GH of < or = 2 mU/l during an OGTT was achieved in 67.4% of patients with intrasellar tumours, compared with 27.3% with extrasellar tumours. Basal GH and post-glucose GH correlated with the late outcome. GH response to TRH showed no correlation with outcome. IGF-1, which could not be assessed in detail, correlated with GH but was not a reliable indicator of outcome. Transsphenoidal adenomectomy is thus a very satisfactory treatment for acromegaly. Postoperative levels of basal growth hormone < 5 mU/l and post-glucose GH < or = 2 mU/l can be regarded as a biochemical cure. Postoperative radiotherapy is not required in patients who achieve a good result. The preoperative factors which significantly influenced the final outcome were basal GH, post-glucose minimum GH, tumour size and impaired pituitary reserve. PMID- 7987658 TI - Cigarette smoking and bone mineral density in older men. AB - Cigarette smoking is cited as having a detrimental effect on bone mineral density (BMD), with associated increased fracture risk. Most of the data are from studies of women, with few studies of men. We examined the relationship between BMD and cigarette-smoking habit in a population-based study of men who were categorized by self-report as 'never smokers', 'current smokers' and 'ex-smokers'. BMD was measured using dual X-ray absorptiometry (DXA). We examined 453 men aged 65-76 years (mean 69.1). Non-smokers ('never' and 'ex' smokers) were heavier than current smokers (p = 0.05). There was no significant relationship between BMD and smoking habit at any site except the trochanter, where current smokers had significantly lower BMD than did non-smokers. However, after adjusting for age and weight there was no longer a significant relationship. BMD did not relate to pack-years of cigarette smoking. Current smokers consumed significantly more alcohol than non-smokers (p = 0.031), but adjusting for alcohol intake did not alter the BMD-smoking relationship. Cigarette smoking appears not to affect BMD in this group of older men. PMID- 7987659 TI - The prevalence of coeliac disease in adult diabetes mellitus. AB - Coeliac disease occurs more commonly in children with insulin-dependent diabetes mellitus (IDDM) than in the general population, but the prevalence of coeliac disease in adults with diabetes is unknown. We therefore screened an adult hospital-based diabetic population using IgA antigliadin antibody (IgA-AGA) to identify those patients requiring intestinal biopsy. In 1 year, 1789 patients (43% IDDM, 57% NIDDM) were screened, and 73 had raised IgA-AGA. Of these patients, 49 agreed to duodenal biopsy and 13 (10 IDDM) had coeliac disease. Selective IgA deficiency was found in eight patients, one of whom had coeliac disease. Of these 14 patients with newly diagnosed coeliac disease, four had microcytic anaemia, nine a low serum ferritin, and four a low albumin-corrected calcium. Eight patients had symptoms which improved on gluten withdrawal. Dietary compliance was maintained in 6/8 symptomatic patients, but only in 1/6 without symptoms. Included in the 1789 patients were four (all IDDM) with known coeliac disease. The overall prevalence of coeliac disease in adult patients with IDDM was 1:50 compared with 1:340 in NIDDM. Coeliac disease is common in adults with IDDM and may cause malabsorption and ill health. It should be suspected in any IDDM patient with gastrointestinal symptoms or unexplained anaemia. PMID- 7987660 TI - Lifestyle and behavioural risk factors associated with asthma morbidity in adults. AB - We studied the association between morbidity and personal lifestyle/behavioural factors that predispose to exposure to known environmental precipitants of asthma, in a group of asthmatics (n = 787) in primary-care clinics. Clinical severity of asthma was determined by questions regarding the frequency of daytime or nocturnal attacks, the number of visits to primary care or hospital emergency departments for treatment of acute attacks, and the number of hospitalizations, as well as the amount of sick leave in the past year. Questions concerning risk factors included ethnicity, clinical atopic status (current rhinitis/eczema), smoking, occupation, keeping of pets, rugs and carpets, use of brooms, burning of mosquito coils or incense, and outdoor air pollution, as well as the patient's knowledge of asthma care. The most significant independent predictors of asthma morbidity, identified from multivariate logistic regression analyses, were current keeping of either pets or rugs/carpets (OR 1.49; 95% CI 1.12-1.99), and current high-risk occupations (OR 0.59, 95% CI 0.40-0.89). A multiplicity of interacting factors and behavioural responses appear to influence the effects of allergens and other environmental precipitants on asthma morbidity in patients. PMID- 7987661 TI - Natural space-use patterns and hippocampal size in kangaroo rats. AB - The size of the hippocampus, a forebrain structure that processes spatial information, correlates with the need to relocate food caches by passerine birds and with sex-specific patterns of space use in microtine rodents. The influences on hippocampal anatomy of sexual selection within species, and natural selection between species, have not yet been studied in concert, however. Here we report that natural space-use patterns predict hippocampal size within and between two species of kangaroo rats (Dipodomys). Differences in foraging behavior suggest that Merriam's kangaroo rats (D. merriami) require better spatial abilities than bannertail kangaroo rats (D. spectabilis). Sex-specific differences in mating strategy suggest that males of both species require more spatial ability than females. As predicted, hippocampal size (relative to brain size) is larger in Merriam's than in bannertail kangaroo rats, and males have larger hippocampi than females in both species. Males of a third species (D. ordii) also have smaller hippocampi than Merriam's kangaroo rat males, despite being similar to Merriam's in brain and body size. These results suggest that both natural and sexual selection affect the relative size and perhaps function of mammalian hippocampi. They also reassert that measures of functional subunits of the brain reveal more about brain evolution than measures of total brain size. PMID- 7987663 TI - Uncoupling of visual and somatic growth in the rainbow trout Oncorhynchus mykiss. AB - Hatchery reared juvenile rainbow trout of common parentage were reared on measured low or high rations, or fed ad libitum for 4.3 months to produce fish with different growth rates. Fish from the different groups differed in size by up to 40 and 290% for length and weight, respectively, by the end of the trial. Slow somatic growth was not accompanied by correspondingly slow growth of either the eyes, optic tectum or the cerebellum, suggesting that above a certain maintenance ration, growth of these parts of the CNS is strongly age-dependent. Retinal characteristics were also found to be age-dependent and not affected by the somatic growth rate of the fish. The corollary that age-dependent ocular growth should also be reflected in different relative eye sizes in fish with differential growth rates in the wild was tested by comparing fish of known age from lakes in which fish have markedly different growth profiles. Fish stocked from a single hatchery were recaptured from Lakes Okataina and Tarawera (rapid fish growth) and Lake Taharoa (slow fish growth) at times up to 5 years after release. As predicted, eye sizes of fish from Lakes Okataina and Tarawera were smaller for any given body size, than those of fish from Lake Taharoa. Absolute eye size was correlated with fish age, although there was some variation in eye size for any given age. Taken together, these results show that up to a certain level of food deprivation, growth of the eye is maintained at the expense, or in spite, of low somatic growth.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7987662 TI - Comparison of the effects of lesions in nucleus basalis and field 'L' on vocal learning and performance in the budgerigar (Melopsittacus undulatus). AB - Lesions were placed in either nucleus basalis (Bas) or the primary thalamorecipient portion of Field 'L' (i.e. centered in Field L2a) in budgerigars at 3-5 weeks posthatching and as adults. The calls of birds sustaining Bas lesions before fledging, or as adults, were markedly abnormal in that they showed little frequency modulation and individual distinctiveness. Call durations, however, were similar for lesioned and unlesioned birds. In contrast, the calls of Field 'L' lesioned birds were similar to those of siblings and cagemates. This implies that the roles of the isthmofrontal (i.e., direct projections from the ventrolateral nucleus of the lateral lemniscus to Bas) and thalamotelencephalic (i.e., direct projections from nucleus ovoidalis thalami to Field L2a) auditory pathways in providing auditory feedback during vocal learning and performance are different and that the isthmofrontal pathway plays an essential role in these processes throughout the life of the animal. PMID- 7987664 TI - Corpus callosum size in delphinid cetaceans. AB - The midsagittal surface area of the corpus callosum was determined by computer assisted morphometry in juvenile and adult members of 13 species of the cetacean family Delphinidae. In 57 brains, absolute callosal areas ranged from 104 to 829 mm2. When compared to other mammal groups possessing a corpus callosum, callosal area in dolphins was smaller in relation to brain mass with a ratio range (mm2/g) of 0.08-0.31. The corpus callosum was decreased relative to brain mass in the larger-brained odontocetes, suggesting that increases in brain size were not necessarily allied with needs for equivalent increases in callosal linkage. One delphinid species, Tursiops truncatus, for which the largest single-species sample was available, was examined for sex differences in callosal size relative to brain mass. Among 10 males and 5 females the averaged ratio was not distinguishable between sexes. PMID- 7987665 TI - The spinal cord of Gymnotus carapo: the electromotoneurons and their projection patterns. AB - The electric organ of Gymnotus carapo lies parallel to the spinal cord and extends from the pectoral girdle to the tip of the tail. The spinal electromotoneurons are distributed in a relatively consistent pattern: there is a peak at 17% of the fish's length and an irregular distribution beyond 25%. Horseradish peroxidase injections into the electric organ not exceeding 5% of the fish's length labeled electromotoneuron arrays occupying 20% of the fish's length. Injections made in four discrete rostrocaudal electric organ regions resulted in labeled electromotoneurons distributed along four sequential but overlapping arrays. Since the caudal portion of the spinal cord lacks electromotoneurons, there is a shortened representation of the electric organ. The electromotoneuron population is not homogeneous: there are small neurons (somata 25-40 microns) and large neurons (somata 45-60 microns) unevenly distributed along the cord. Small neurons occur at more rostral spinal cord segments, while large neurons lie in more caudal segments. Both kinds of nerve cells coexist in the intermediate regions. Overlapping of subsequent neuronal arrays favors synchronized firing of electrocytes. The presence of two neuronal populations differing in size and projecting to opposite electrocyte faces may account for the timed excitation of the electrogenic surfaces. Taking into account these new findings a comprehensive explanation of the activation sequence along the spinal cord and the electric organ is proposed. PMID- 7987666 TI - Monoaminergic innervation patterns in the anterior dorsal ventricular ridge of a lacertid lizard, Psammodromus algirus. AB - In contrast to the view of a diffuse monoaminergic innervation of the telencephalon, studies on the monoaminergic innervation in certain mammalian isocortical regions have shown a high degree of regional and laminar specificity. The present study was designed to examine the distribution patterns of dopamine, noradrenaline and serotonin in a telencephalic structure, the anterior dorsal ventricular ridge, of the sand lizard Psammodromus algirus (Lacertidae) using specific antibodies against each monoamine. The anterior dorsal ventricular ridge receives an abundant monoaminergic innervation compared to that of cortical telencephalic regions. The distribution of the different monoamines presented zonal and regional patterns throughout the ridge. The cell cluster zone was profusely innervated by catecholamines, whereas no serotoninergic fibers innervated the cell bodies in the cluster zone. On the other hand, the periventricular zone was heavily innervated by serotonin, but catecholaminergic fibers were almost lacking. With regard to regional patterns, dopamine exhibited major differences in the mediolateral axis of the anterior dorsal ventricular ridge: dopaminergic innervation was densest in the lateral region, which in other reptiles is described as a target of visual thalamic projections. Whereas the zonal pattern of the monoaminergic innervation of the anterior dorsal ventricular ridge seems to be a constant feature in the reptiles studied to date, the regional pattern varies among reptilian groups, especially taking into account the density of monoaminergic innervation. PMID- 7987667 TI - Administration of human chorionic gonadotropin affects sleep-wake phases and other associated behaviors in cycling female rats. AB - We investigated the possible effects of human chorionic gonadotropin (hCG) on sleep-wake phases and other associated behaviors controlled by the medial preoptic area, cerebral cortex and hippocampus. Chronic epidural electroencephalographic (EEG) and temporal muscle electromyographic (EMG) electrodes were placed in cycling female rats. After a week of recovery, rats were injected intraperitoneally at 3.00 pm on the day of proestrus with either saline or highly purified hCG or indomethacin or hCG plus indomethacin. Three hours after injection, EEG, EMG and behavioral activities were recorded for 3.5 h. The administration of hCG increased high and low amplitude sleep, resting phase and decreased active awake phase, walking, sniffing and chewing as compared to the controls. While the administration of indomethacin alone had no effect, coadministration inhibited hCG effects. Medial preoptic area, cerebral cortex and hippocampus contain immunostaining for LH/hCG receptors. The administration of hCG resulted in an increase of immunoreactive PGD2 and a decrease of PGE2 in median preoptic area, cerebral cortex and hippocampus as compared to the controls. In summary, hCG administration affects sleep-wake phases and other associated behaviors in rats which can collectively be described as decreased activity. These effects are probably mediated by increasing PGD2 and decreasing PGE2 in areas of brain which control these activities. The above findings may be relevant to pregnant women who experience decreased activity when hCG is present in the circulation and cerebrospinal fluid. PMID- 7987668 TI - In vivo treatment with mu and delta, but not kappa-selective opioid agonists reduces [3H]spiperone binding to the guinea-pig striatum: autoradiographic evidence. AB - In guinea-pigs, acute treatment with mu and delta receptor opioid agonists induces sedation and immobility [1,5], and attenuates the behavioural activation produced by the dopamine D2 agonist quinpirole [5]. In contrast, kappa-selective opioid agonists induce dystonic-like movements [4,5,8]. This has led us to investigate the possibility of an interaction between acute opioid treatment and the dopamine D2 system. The effect of acute treatment with mu, delta and kappa opioid agonists on [3H]spiperone binding sites (dopamine D2) in guinea-pig brain was studied using receptor autoradiography. The mu preferring agonist morphine (15 mg/kg subcutaneously, SC) given for 2 h, and the delta receptor selective agonist DPDPE (Tyr-D-Pen-Gly-Phe-D-Pen) (20 nM, intracerebroventricularly, ICV) given for 0.5 h, both decreased the density of specific (butaclamol displaceable) [3H]spiperone binding in the caudate putamen by 23.8 +/- 1.7% and 24.2 +/- 2.7% respectively, and in nucleus accumbens by 26.1 +/- 2.7% and 21.9 +/- 4.6% respectively compared to saline treated animals. There were no significant changes in the level of [3H]spiperone binding to other brain regions examined including frontal cortex, hippocampus, substantia nigra, ventral tegmental area, amygdala, hypothalamic nuclei and cerebellum. In other experiments, incubation of coronal slices from various brain regions with [3H]spiperone, in the presence of a high concentration of morphine (20 microM) or DPDPE (10 microM) did not affect the level of binding, thus precluding effects due to residual tissue levels of drugs after in vivo treatment.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7987669 TI - Cytokines, prostaglandins and lipocortin-1 are present in the brains of scrapie infected mice. AB - The presence of cytokines, prostaglandins and lipocortin-1 was investigated in terminally affected mice in two models of scrapie. There was marked induction of glial interleukin-1 beta, tumour necrosis factor alpha, prostaglandin E2, prostaglandin F2 alpha and lipocortin-1 immunoreactivity in those areas of the brain showing the characteristic vacuolation of scrapie. A comparison of these staining patterns with those of GFAP and F4/80 showed that their expression occurred predominantly in astrocytes. It is possible that cytokines play a significant role in the pathogenesis of neurodegeneration in scrapie. PMID- 7987670 TI - Use of Fos-related antigens (FRAs) as markers of neuronal activity: FRA changes in dopamine neurons during proestrus, pregnancy and lactation. AB - This manuscript describes the use of staining of Fos-related antigens (FRAs) as markers for changes in neuronal activity. The model system consisted of the tuberoinfundibular dopamine (TIDA) neurons located in the arcuate nucleus of the hypothalamus. Under normal conditions, these neurons are devoid of c-Fos staining even though the neurons are tonically active and can express FRAs. During specific neuroendocrine states the neurons undergo changes in activity, as described by other studies. At times when the activity is relatively high as in pregnancy and during proestrus, approximately 50%-60% of the TIDA neurons expressed FRA immunoreactivity. Moreover changes over the course of proestrus paralleled known shifts in TIDA activity (declining as the day progressed). At times when TIDA activity is suppressed, such as during lactation, FRA staining in TIDA neurons was markedly reduced or absent. Upon removal of the suckling stimulus, FRA staining rose to reach peak expression 12-24 h after pup removal (without coordinate induction of c-Fos). These data suggest that FRA staining can serve as a useful marker of activity in the TIDA neurons which permits not only assessment of stimulated activity but also suppressed function in the neurons. A cautionary note in using this approach along with acquisition of serial blood samples for hormone measurement is that surgical procedures for monitoring plasma hormone levels are associated with strong long-lived induction of FRAs (and c Fos) in many neurons (including the TIDA neurons) that can confound interpretation of FRA staining. PMID- 7987671 TI - Intracerebroventricular administration of angiotensin II increases heart rate in the conscious trout. AB - The central effect of angiotensin II on cardiovascular activity has been investigated in conscious trout bearing an intracerebroventricular (i.c.v.) cannula and an intra-arterial catheter. I.c.v. injection of the angiotensin II agonist [Asn1,Val5]AII (6.2-50 pmol) induced a dose-dependent increase in heart rate and arterial blood pressure. Central administration of the angiotensin II antagonist DuP 753 (5 nmol) 30 min before i.c.v. injection of [Asn1,Val5]AII totally prevented the tachycardia and reduced the hypertension induced by the angiotensin II agonist. Intra-arterial injection of arginine-vasotocin (12.5 pmol) caused a bradycardia associated with a marked increase in arterial blood pressure. I.c.v. injection of [Asn1,Val5]AII totally blocked the bradycardia induced by arginine-vasotocin and this effect was prevented by central administration of DuP 753. In contrast, [Asn1,Val5]AII did not affect the increase in blood pressure induced by arginine vasotocin. Suppression of the vagal tone by atropine treatment totally blocked the central effect of [Asn1,Val5]AII. These results show that angiotensin II acts directly on the trout brain to increase blood pressure and heart rate. The effect of angiotensin II is mediated through a receptor related to the mammalian AT1 receptor type. PMID- 7987672 TI - Immunohistochemical localization of kappa opioid receptors in the human frontal cortex. AB - The cellular and subcellular kappa opioid receptor distribution in human frontal cortex was studied using the monoclonal antibody (KA8). kappa opioid receptor like immunoreactivity was mainly localized in pyramidal neurons of layers II/III and V. In addition, some round and ovoid neurons were found immunolabeled mainly in layer VI. At the ultrastructural level the immunoprecipitate was attached to the cell membrane but was not associated with synaptic specializations. Furthermore, labeling was present in the neuronal perikarya associated with free ribosomes and in the dendrites partly decorating microtubular structures. Previous autoradiographic findings remained restricted to the level of laminar distribution. By contrast, the monoclonal antibody KA8 provides a unique tool to study the cerebral kappa opioid receptor distribution on the cellular and subcellular level. PMID- 7987673 TI - Hageman factor and its binding sites are present in senile plaques of Alzheimer's disease. AB - Hageman factor (HF) or factor XII participates in several defense systems of the body. These include coagulation, fibrinolysis and complement activation. We investigated the expression of HF and its mRNA in control and Alzheimer's disease (AD) brain, using immunohistochemistry and polymerase-chain reaction (PCR) techniques. HF mRNA was detected in control and AD brain extracts, indicating that HF can be produced by endogenous brain cells. HF-like immunoreactivity was present in residual serum of capillaries in both control and AD brain, consistent with its known presence in the circulation. In addition, AD senile plaques were stained. The staining was dramatically enhanced when AD sections were incubated with solutions containing HF, indicating that plaques contain not only HF but also binding sites for HF. The enhanced staining was eliminated by pretreatment of solutions with the HF-binding agent kaolin. It was also eliminated by pretreatment of sections with protamine, an agent which strongly binds to negative surfaces. These data suggest that negatively charged surfaces in plaques might bind HF in vivo. Since HF can be activated by contact with negative surfaces, locally released HF could be playing a role in initiating a variety of inflammatory responses in AD brain. PMID- 7987674 TI - Extensor- and flexor-like modulation within motor pools of the rat hindlimb during treadmill locomotion and swimming. AB - EMG activity was recorded from the vastus lateralis (VL, knee extensor), rectus femoris (RF, hip flexor and knee extensor), tibialis anterior (TA, ankle flexor and digit extensor) and either the lateral or medial gastrocnemius (LG, MG, knee flexors and ankle extensors) muscles of 7 adult rats during treadmill locomotion and swimming. Most flexors and extensors are activated as a single burst but each is known to be modulated differently during locomotion. For example, the extensor EMG bursts are shortened and amplitude elevated as speed increases, whereas little change occurs in the EMG duration and amplitude in flexors. The RF and VL displayed a double burst of EMG activity per cycle during treadmill locomotion and a single burst during swimming. Kinematic and EMG analyses showed that during running, one of these EMG bursts occurred primarily during swing while the other burst occurred primarily during stance. Modulation of the burst occurring during swing approximated a flexor pattern, while the second burst was modulated like a typical extensor when running over a range of speeds and grades on a treadmill. These data suggest that motoneurons within a motor pool of a uniarticular (VL) as well as a biarticular (RF) muscle can be modulated by more than one cyclical input, probably of central origin, and that under some conditions several motor pools may share the same central commands. PMID- 7987675 TI - Enhancement of memory processing in an inhibitory avoidance and radial maze task by post-training infusion of bombesin into the nucleus tractus solitarius. AB - Bombesin is a peptide known to modulate memory storage when given either systemically or intraventricularly immediately after training. Two experiments were conducted to determine whether the nucleus of the solitary tract (NTS) mediates the effects of bombesin on memory. In the first experiment male Sprague Dawley rats were trained in an inhibitory avoidance task (0.35 mA, 0.5 s footshock) and bombesin or vehicle was infused unilaterally into the NTS through implanted cannulae immediately after training. Retention was assessed either 2 or 7 days later. Doses of 25 or 50 ng of bombesin significantly enhanced retention on the 2 day test (P < 0.05 and 0.01 compared with vehicle controls, respectively). There were no differences between the drug and control groups on the 7 day retention test. In the second experiment, bombesin (25, 50, or 250 ng) or vehicle was infused unilaterally into the NTS immediately after the animals were trained in a win-shift radial arm maze task. On retention tests given 18 h later, groups that received 25 ng or 50 ng of bombesin made a significantly greater percentage of correct choices on the retention test than did the vehicle treated controls (P < 0.02 and P < 0.05, respectively). The findings indicating that bombesin influences retention by activating the NTS is consistent with recent evidence suggesting that the NTS is involved in regulating memory storage. PMID- 7987676 TI - Delayed and prolonged post-ischemic hypothermia is neuroprotective in the gerbil. AB - Global ischemia, in the gerbil, produces profound hippocampal CA1 loss which leads to functional abnormalities (e.g. habituation impairment). In experiment 1, gerbils were subjected to 3 or 5 min of normothermic (brain) ischemia. Hypothermic groups were cooled to 32 degrees C for 12 h beginning 1 h after ischemia, while control groups (no hypothermia) regulated their own temperature. Exploration in a novel open field was assessed on days 3, 7 and 10 following ischemia and CA1 neurons were counted after 10- or 30-day survival. Both ischemia durations produced severe CA1 necrosis which resulted in increased open field activity. Hypothermia attenuated this behavioral pattern and substantially reduced CA1 necrosis against 3 min of ischemia when assessed at 10 and 30 days, but was only partially effective against a 5 min occlusion where, in addition, some cell death appeared to be delayed rather than prevented. In experiment 2, gerbils were occluded for 5 min and survived for 30 days. Twenty-four hours of hypothermia initiated 1 h after ischemia resulted in near total preservation of CA1 neurons. Thus, increasing the duration of post-ischemic hypothermia from 12 to 24 h produced much greater neuroprotection against severe ischemia. Prolonged post-ischemic hypothermia may be a valuable intervention in stroke patients. PMID- 7987677 TI - Effect of lactic and CO2 acidosis on neuronal function following glucose-oxygen deprivation in rat hippocampal slices. AB - The present study was designed to determine whether lactate changes the critical pH point at which the recovery of rat population spike is inhibited following glucose-oxygen deprivation and second, which degree of lactic acidosis is similar to the effect of CO2 acidosis. The population spike was recorded from the hippocampal CA1 region after stimulation of the Schaffer collaterals. Slices were randomly perfused with various acidotic solutions for 30 min. During the last 15 min, glucose-oxygen deprivation was combined with the acidotic perfusion. Then the hippocampal slices were perfused with a standard solution of pH 7.4 for 60 min and recovery was compared to the control population spike and expressed as a percentage of the control value. In the control acidotic solution, the critical pH point was 5.0. When 15 mM or 30 mM lactate were added to the control solution, the critical pH point changed to 5.5 or 6.0, suggesting that the inhibition of the population spike was enhanced by lactate in a dose-dependent fashion. The recovery of the population spike was inhibited by exposing the slices to CO2 of 25% or above (pH was 5.76 or below) and this inhibition of recovery associated with CO2 acidosis was the same degree as occurred with 30 mM, namely severe lactic acidosis. PMID- 7987678 TI - Glycine and GABAA antagonists reduce the inhibition of primate spinothalamic tract neurons produced by stimulation in periaqueductal gray. AB - Amino acids are demonstrated to be important neurotransmitters mediating the inhibitory transmission from nucleus raphe magnus to spinal nociceptive dorsal horn neurons. In this study, the role of glycine and GABA in the inhibitory processes evoked by stimulation in periaqueductal gray (PAG) of responses of primate spinothalamic tract (STT) neurons to cutaneous mechanical and thermal stimuli was investigated by examining the effects of strychnine and bicuculline, antagonists of glycine and GABAA receptors, respectively, introduced into the dorsal horn through a microdialysis fiber. The inhibitory effects of iontophoretic application of glycine and GABAA agonists on STT cell activity evoked by noxious mechanical stimulation of the skin were selectively blocked by their specific antagonist, strychnine or bicuculline, infused into the dorsal horn. Similarly, intra-spinal application of strychnine or bicuculline resulted in a significant reduction in the PAG stimulation-induced inhibition of responses of STT cells to cutaneous stimuli. This reduction was mainly on the PAG-induced inhibition of the responses to noxious mechanical stimuli. Our results suggest that glycinergic and GABAergic inhibitory interneurons in the spinal cord dorsal horn synapsing on STT cells are activated during stimulation in PAG and contribute to descending antinociceptive actions. PMID- 7987679 TI - Axonal reinnervation does not influence Schwann cell proliferation after rat sciatic nerve transection. AB - We asked whether reinnervating axons are Schwann cell mitogens in vivo as they are in vitro. Left sciatic nerves of 50 Wistar rats were transected. In one-half of the animals, axonal reinnervation from the proximal to the distal stump was allowed to take place, while in the other half, sutures were placed on the transected nerve ends to prevent reinnervation. Samples were collected from 3 days up to 8 weeks after the transection proximally and distally from the point of transection. PCNA-immunostaining was performed on paraffin sections to determine the number of proliferating cells. Axonal reinnervation was followed by Bielschowsky staining and Schwann cell number was determined by counting S-100 immunopositive cells from paraffin sections. In the distal stump Schwann cell proliferation was similar in both experimental groups. There was no statistical evidence of S-100 negative cell proliferation during the study. Proximally to the site of transection the number of small initial axonal sprouts and also the number of Schwann cells increased if the nerve stump had been sutured. In conclusion, although axons may be mitogenic for Schwann cells, axonal reinnervation into the distal stump of the transected peripheral nerve does not influence the proliferation of Schwann cells to a greater extent than other potential effects associated with nerve transection. PMID- 7987680 TI - Comparative effect of alpha-MSH and b-FGF on neurite extension of fetal rat spinal cord neurons in culture. AB - Basic fibroblast growth factor (b-FGF) and alpha melanocyte stimulating hormone (alpha-MSH) were tested for their ability to promote axonal elongation on E14 fetal rat spinal cord cell culture, and to support cell survival. A similar development of neurite was observed in alpha-MSH treated cultures or in control cultures, with an axonal length ranging from 87.50 microns to 195.60 microns on day 3. Complete cell death occurred after 6 days of incubation. Whatever the concentration of b-FGF used (0.312-2.5 ng/ml), a significant increase (1.2- to 1.4-fold) in neurite length was observed, with neuronal survival up to 9 days. PMID- 7987681 TI - Actions of 5-hydroxytryptamine on ventral tegmental area neurons of the rat in vitro. AB - Intracellular recordings were made with conventional microelectrodes and with whole-cell patch-clamp electrodes from neurons of the rat ventral tegmental area and substantia nigra zona compacta in vitro. Neurons were distinguished as principal cells and secondary cells; it is known from previous work that most principal cells contain dopamine whereas secondary cells do not. 5 Hydroxytryptamine (5-HT; 3-100 microM) depolarized (or evoked an inward current at -60 mV) 46% of 153 principal cells; a small proportion (11%) of cells were hyperpolarized (or showed outward current at -60 mV). Secondary cells were equally likely to be depolarized (or inward current at -60 mV, 30% of 80 cells) or hyperpolarized (or outward current at -60 mV, 28%). approximately 40% of each type of cell were unaffected by 5-HT. Depolarizing responses of 5-HT were mimicked by (+/-)-1-(2,5-dimethoxy-4-iodophenyl)- 2-aminopropane (DOI) and blocked by ketanserin. Hyperpolarizing responses were mimicked by dipropyl-5 carboxamidotryptamine and reversed polarity at the K+ equilibrium potential. Inhibitory postsynaptic potentials (or currents) mediated at GABAA receptors occurred spontaneously in some principal cells; they were reversibly blocked by tetrodotoxin and bicuculline. 5-HT either increased or decreased the frequency of these synaptic potentials but did not change their mean amplitude or decay time.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7987682 TI - Water deprivation and subfornical organ activity in the pigeon a [14C]2 deoxyglucose study. AB - Following varying degrees of water deprivation (0, 24 and 72 h), functional activity in the subfornical organ (SFO) of pigeons was measured using the [14C]2 deoxyglucose method. Increasing levels of water deprivation produced a significant increase in glucose uptake in SFO. The magnitude of the effect was systematically correlated with morphologically defined SFO subdivisions. PMID- 7987683 TI - Ethanol neurotoxicity in vitro: effects of GM1 ganglioside and protein synthesis inhibition. AB - Cultures of septal and hippocampal neurons from fetal rat and dorsal root ganglion neurons from embryonic chick were pretreated with GM1 ganglioside or cycloheximide and then supplemented with toxic concentrations of ethanol. GM1 provided significant protection against ethanol neurotoxicity in each population. The inhibition of protein synthesis by cycloheximide, however, which protects against cell death resulting from withdrawal of neurotrophic factor support, did not ameliorate ethanol-induced neuronal loss. PMID- 7987684 TI - Inhibition of glutamate uptake in the rostral ventrolateral medulla enhances baroreflex-mediated bradycardia in conscious rats. AB - The current investigation tested the hypothesis that inhibition of L-glutamate uptake in the rostral ventrolateral medulla (RVL) enhances the baroreceptor mediated heart rate responses. In conscious freely moving rats, unilateral microinjection of the L-glutamate uptake blocker p-chloromercuriphenylsalfonic acid (PCMS, 0.1 nmol) elicited a 45% increase in the baroreflex-mediated bradycardic response tested by i.v. phenylephrine (-2.0 +/- 0.1 vs -2.9 +/- 0.2 beats/min/mmHg). In the same rats, evidence for the ability of PCMS to inhibit L glutamate uptake at the site of its microinjection in the RVL was obtained. PCMS microinjected into the RVL did not influence basal blood pressure and heart rate. However, the cardiovascular responses elicited by L-glutamate (5 nmol) microinjected into the RVL were significantly enhanced by PCMS pretreatment. The pressor and bradycardic responses to L-glutamate increased 53% (from 28.3 +/- 2.4 to 43.4 +/- 4.7 mmHg) and 68% (from -59.6 +/- 13.1 to -100.0 +/- 7.2 beats/min), respectively after PCMS. An equal volume of ACSF microinjected into the RVL had no effect on BRS (-2.1 +/- 0.2 vs -1.9 +/- 0.1 beats/min/mmHg), nor on the pressor (29.9 +/- 7.4 vs 30.6 +/- 4.4 mmHg) and bradycardic (-50.3 +/- 12.0 vs 43.3 +/- 12.0 beats/min) responses elicited by L-glutamate. These findings suggest that: (i) glutamatergic pathways in the RVL serve a facilitatory role in processing the baroreceptor information, and (ii) L-glutamate uptake mechanisms exert a restraining influence on BRS and the cardiovascular effect of L glutamate. PMID- 7987686 TI - Glutamate elicits an outward K+ current which is normally suppressed by a Ca2+/calmodulin-dependent protein kinase II. AB - The inhibitory action of glutamate (Glu) was examined in identified Euhadra neurons, using the voltage-clamp method in combination with the pressure injection technique. Glu elicited a slow outward K+ current (Glu current) whose amplitude was dose-dependent. This current was inhibited by exogenous Ca2+/calmodulin-dependent protein kinase II (CaMKII) and is enhanced by a specific CaMKII inhibitor. However, no significant changes in the Glu current were observed when the catalytic subunit of protein kinase A (PKA) or the protein kinase C (PKC) fragment (530-558) was intracellularly applied; or using a PKA inhibitor or a PKC inhibitor. Neither the antagonists of the Glu receptor, D-2 amino-5-monophosphonovalerate, 6-cyano-7-nitroquinoxaline-2,3 dione and kynurenic acid, nor the G protein blockers, pertussis toxin and chorela toxin, had any significant effect on the Glu current. These results indicate that Glu opens the CaMKII-suppressing K+ channels, suggesting a novel Glu-induced inhibitory mechanism. PMID- 7987685 TI - Responses of cerebral arterioles to N-methyl-D-aspartate and activation of ATP sensitive potassium channels in old rats. AB - The first goal of this study was to examine the hypothesis that aging impairs dilator responses of cerebral arterioles to N-methyl-D-aspartate (NMDA). The second goal was to determine whether aging impairs vasodilatation in response to activation of ATP-sensitive K+ channels. Diameter of cerebral arterioles was measured through a cranial window in anesthetized adult (5 +/- 1 (mean +/- S.E.) months old) and old (26 +/- 1 months old) Fischer 344 rats. In adult rats, NMDA (10 and 100 microM) dilated pial arterioles by 14 +/- 5 and 72 +/- 9%, respectively, from a control diameter of 36 +/- 5 microns. Aprikalim (1 and 10 microM), a direct activator of ATP-sensitive potassium channels, dilated cerebral arterioles in adult rats by 14 +/- 3 and 49 +/- 6%, respectively. Vasodilatation in response to NMDA and aprikalim were similar in old and adult rats. Thus, in contrast to impaired cerebral vasodilator responses to some stimuli, responses of cerebral arterioles to NMDA and activation of ATP-sensitive potassium channels are preserved in old Fischer 344 rats. PMID- 7987687 TI - Statistical significance of amino acid sequence similarity in type II DNA methyltransferases. AB - The statistical significance of amino acid sequence similarities previously observed in type II DNA methyltransferases has been investigated. It is shown: (1) that the intramolecular similarities observed among various type II Mtases are not statistically significant and thus can not be used to support a gene duplication model; (2) that the intermolecular similarities observed in a peptide in various type II adenine methylases are statistically confirmed; (3) that the similarities observed between MutH and these proteins for this peptide are not statistically significant and therefore cannot be used to propose a functional role in DNA recognition for this peptide. PMID- 7987688 TI - [Morphological characterization of cell lines of human uveal melanoma]. AB - Several cell lines have been derived from an ocular melanoma obtained from an enucleated patient. Three cell types are observed during the time in culture of all the cell lines under study. Two of them have epithelial and spindle shape respectively. A third cell type, having a spheroidal shape, is formed from spindle cells and may be transformed into epithelial cells upon re-seeding. Further experiments showed that the same cell may change of shape following the cycle: spheroidal-->epithelial-->fusiform-->spheroidal. Scanning microscopy shows the coexistence of the three cell shapes in the same culture and the presence of several filaments and processes protruding at the surface of the cells. Transmission electron microscopy shows that the cell lines, in general, contain melanosomes empty or fairly pigmented and several filaments and microtubules. The presence of melanin may be stimulated by seeding of melanoma cells over a "feeder layer" of fibroblasts. PMID- 7987689 TI - [Use of a body condition index (BCI) for the study of the reproduction in snakes]. AB - A body condition index (BCI = actual body mass/optimal theoritical body mass of the studied animal) was estimated in females of 3 species of snake. From dissections of 88 Vipera aspis and 18 Coluber viridiflavus, strong relationships between body reserves (such as mass of fat bodies and liver) and BCI were found. Furthermore, BCI explained most of the variance in the mass of the fat bodies and in the mass of the liver; however BCI and body length together increased the percentage of variation explained. Thus, a satisfactory estimation of body reserves in relation to body length is possible in living snakes. We have studied reproductive parameters (clutch size and litter size) in Vipera aspis (Viperidae) and Elaphe longissima (Colubridae) during a 3 year period. In the two species positive relationships between maternal body length and number of offspring were found. At the beginning of vitellogenesis, litter size is related to the BCI level in V. aspis but not in E. longissima. In both species, BCI must exceed a threshold value for reproduction to take place. However this threshold value is much lower in E. longissima (0.55) than in V. aspis (0.70). This indicates that in the latter species, large body reserves are necessary for the induction of vitellogenesis. In E. longissima, maternal body length is an important determinant of reproductive success, body reserves playing a minor role. In contrast, in female V. aspis the reproductive success is related to BCI and to a lesser extent to body length.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7987691 TI - Fast protein sequence verification by matrix assisted laser desorption mass spectrometric analysis of whole enzymatic digests. AB - Matrix assisted laser desorption mass spectrometry provides a very fast and efficient way to check protein sequences by the analysis of whole proteolytic digests. This method has been applied to the sequence verification of E. coli isoleucyl tRNA synthetase, for which two different sequences are found in data banks. The result of this investigation clearly shows that no one of these sequences is correct. PMID- 7987690 TI - A new open reading frame, encoding a putative regulatory protein, in Agrobacterium rhizogenes T-DNA. AB - We report the presence of an open reading frame, named ORF13a, encoding a putative regulatory protein on the T-DNA of Agrobacterium rhizogenes 8196 Ri plasmid. Homologous ORFs are present at the same location in two other types of Ri plasmids. We present evidence that ORF13a is transcriptionally active. Expression of ORF13a was investigated by analysis of glucuronidase (GUS) activity in transgenic tobacco containing an ORF13aGUS fusion. The gene fusion was expressed at higher level in roots than in leaves. The putative protein encoded by ORF13a has an isoelectric point of 11.55 and carries SPXX repeated motifs suggesting a possible regulatory function for this gene. PMID- 7987692 TI - [Activity of W-sex heterochromatin and accumulation of the nuage in nurse cells of the lepidopteran Ephestia]. AB - In the Lepidopteran Ephestia, in the female sex, the W chromosome, with which no function is known to be associated, is, in whole or part, maintained in a heterochromatic state in all cellular categories, except for the oocyte. In the present work, however, W-sex heterochromatin (W-SH) is demonstrated by ultrastructural autoradiography to be transcriptionally active in nurse cells during previtellogenesis. This activity is accompanied by accumulation of "nuage" in the perinuclear cytoplasm, both phenomena arresting at the beginning of vitellogenesis. We have performed kinetic analysis of the labeling associated with W-SH and with nuage through a pulse-chase experiment, together with high resolution examination of the structures visible in the vicinity of active W-SH. Our results suggest that W-SH transcripts are packaged and transported to the cytoplasm within polyparticles typically resembling the hnRNP particles--the structures packaging (pre)messenger RNA which are isolated from the nuclei of numerous Eukaryotes--and that they are concentrated within the nuage upon leaving the nucleus. Such findings explain the close relationship observed in Ephestia, both in space and time, between the nuage and active W-SH. In different organisms, including Drosophila, the nuage has been proposed to be a site of assembly of germ plasm. Considering this hypothesis as well as our results with Ephestia, we speculate that the activity of W-SH detected in nurse cells reflects the expression of one or several genes located within the heterochromatin of the W chromosome, and that the function of these genes is related with the elaboration of germ plasm. The implications raised by these unexpected proposals are mentioned. PMID- 7987693 TI - [Evidences for genetic transmission of pulse arterial pressure]. AB - Systolic (PS), diastolic (PD), and pulse (PULS) arterial blood pressure were examined in 151 French-West-Indies families. After adjustment for sex, age, Na/K urinary ratio, alcohol consumption, use of anti-hypertensive drug, the distributions of PS and PD were correctly fitted by two commingled normal distributions, one of them including 5% of the highest values of blood pressure which have to be compared to the high prevalence of hypertension in this population (10 to 20%). By performing segregation analyses under Lalouel et al.'s unified model we do not support any genetic transmission for PS and PD. On the contrary, large evidence for genetic transmission of PULS was found, involving one locus, two equally frequent alleles. However dominance cannot be correctly inferred. Accordingly, PULS appears to be of larger interest than PS and PD to study the genetic regulation of the arterial blood pressure. PMID- 7987694 TI - Genetic heterogeneity of severe childhood autosomal recessive muscular dystrophy with adhalin (50 kDa dystrophin-associated glycoprotein) deficiency. AB - Severe autosomal recessive muscular dystrophy (SCARMD), McKusick n. 253700, has been originally described in North-African populations, in which significant linkage has been established with DNA markers mapping to the proximal region of the long arm of chromosome 13, without evidence for heterogeneity of the SCARMD locus in these populations. A striking feature of this disease is the isolated deficiency of adhalin, a sarcolemmal 50 kDa dystrophin-associated glycoprotein. We report a non-inbred French family with a milder progressive form of muscular dystrophy affecting subjects of both sexes. The parents are not affected suggesting an autosomal recessive transmission. In 4 siblings displaying mild to overt clinical signs of muscular dystrophy, serum creatine kinase was high, and muscle specimens showed variable degree of necrosis-regeneration with little fibrosis. In the 4 cases adhalin was completely absent in muscle sections, whereas dystrophin and the other members of the dystrophin-associated protein complex were normal, except for the 35 kDa dystrophin-associated glycoprotein which was decreased as usually observed in SCARMD. Linkage and homogeneity analysis using 4 microsatellite markers of chromosome 13q that are linked to the North-African SCARMD locus were performed in this family. Results show that the morbid locus involved in this family does not map to the same region as the SCARMD locus. This second locus may be involved in sporadic cases of muscular dystrophy with adhalin deficiency that have been reported in Europe. PMID- 7987695 TI - [Study of the membrane expression of TcR/CD3 complex using somatic cell mutants]. AB - T lymphocytes express membrane antigen receptor TcR/CD3 complexes only when all subunits are correctly assembled. Studies on TcR/CD3 membrane negative T cell variants containing all necessary subunits intracellularly, may allow to identify amino acids important for different subunit interactions. In this review, we summarize our recent work on TcR/CD3 negative variants of the human T cell line Jurkat. We found two critical amino acids in the TcR-alpha and TcR-beta extracellular constant regions (phenylalanine n. 216 and intrachain disulfide cysteine n. 212) involved in TcR-alpha beta/CD3- gamma epsilon, delta epsilon intermediary complex/zeta 2 homodimer interactions: (1) amino acid exchanges of phenylalanine demonstrated the importance of an aromatic amino acid residue at this position; (2) the intrachain disulfide bond assures a tertiary structure of the constant domain that is necessary for association with zeta 2 homodimers. PMID- 7987696 TI - Enantiomeric 2',3'-dideoxycytidine derivatives are potent human immunodeficiency virus inhibitors in cell cultures. AB - 2',3'-dideoxy-beta-L-cytidine (beta-L-DDC) and its 5-fluoro derivative (beta-L-5 F-DDC) have been stereospecifically synthesized by a multi-step reaction sequence from L-xylose and their anti-HIV properties examined. Among these two L enantiomers, the hitherto unknown beta-L-5-F-DDC emerged as a potent anti-HIV-1 and HIV-2 compound in different cell culture systems, with selectivity indices similar or superior to those of the currently licensed drug DDC which has the natural beta-D configuration. PMID- 7987697 TI - [Experimental study of different histologic types of pulmonary cancers induced by irradiation]. AB - Recent epidemiologic studies suggested that some histologic types of carcinomas were preferentially induced in the lung by irradiation, whatever the mode of exposure and the radiation quality. Since smoking and other environmental airborne pollutants may be strong confounding factors in humans, we have investigated whether histological subtypes were dependent or not on the mode of exposure, in a large series of 9000 rats exposed to external and internal sources at high and low Linear Energy Transfer. Despite comparable overall risk coefficients in rats and humans, our results show that histological types are influenced not only by dose but also by radiation quality and heterogeneity of dose delivering. We suggest that extrapolation from one group to an other take this information in consideration. PMID- 7987698 TI - [Antiviral effect of recombinant interferon-alpha on hepatitis A virus replication in human liver cells]. AB - Two recombinant interferons-alpha (IFNs-alpha) were assayed for their antiviral effect on hepatitis A virus (HAV) replication in the human hepatoma cell line PLC/PRF/5. IFN alpha-2a and IFN alpha-2b resulted in concentration-dependent inhibition of HAV antigen expression and HAV infectivity at non toxic concentrations. Their selectivity indices, calculated as the ratio of the dose that reduced the number of viable cells to 50% (CD50) to the effective dose that inhibited 50% of viral antigen expression (ED50) were > 1000. Recombinant IFN alpha emerged, from the present study, as a promising candidate for chemotherapy of hepatitis A. PMID- 7987699 TI - On the mechanism of biotin synthase of Bacillus sphaericus. AB - A cell-free system of a bioB transformant of Bacillus sphaericus, effecting the last step of biotin biosynthesis, namely the introduction of sulfur into dethiobiotin has been recently described. S-adenosyl methionine (SAM) is absolutely necessary for activity. We show here, through experiments with [35S]SAM and [35S]Cys, that the sulfur donor is not SAM but probably cysteine (Cys) or a derivative. This finding together with the fact that NADPH and FAD are required for activity leads us to postulate some analogy between the biotin synthase system and other systems which use SAM as a source of desoxyadenosyl radical. PMID- 7987700 TI - Adenovirus insertion encoding the Lac Z gene in human nervous cells in primary dissociated cultures. AB - Primary dissociated cultures of human fetal central nervous system cells were prepared and inoculated at different days in vitro with adenovirus that contained a reporter gene encoding beta-galactosidase. At various time intervals, the cultures were processed for characterization with X-gal histochemistry and additional immunostaining with neurofilament (NF), GABA and glial fibrillary acidic protein (GFA-P). We observed that NF (+) and GABA (+) neuronal as well as GFA-P (+) glial cells could express beta-galactosidase activity after inoculation. The labeling was detected up to 3 months after virus treatment. In addition, neurons cultivated for three months were found to be still permissive for virus infection. We can conclude that adenovirus may be considered as a potential vector to transfer genes to nerve cells. PMID- 7987701 TI - Lipopolysaccharide induces sickness behaviour in rats by a vagal mediated mechanism. AB - To assess the possibility that lipopolysaccharide (LPS) induces sickness behaviour by activating primary afferent nerves, the effects of LPS (1.25 mg kg 1, intraperitoneally) were compared in vagotomized and sham-operated rats. Subdiaphragmatic vagotomy blocked the LPS-induced depression of social investigation but had no effect on LPS-induced increases in levels of IL-1 beta in plasma and peritoneal macrophages and on LPS-induced changes in dehydrogenase activity of peritoneal macrophages. PMID- 7987702 TI - [Effects of moderate noises on early auditory evoked potentials in man, in relation to age]. AB - Thirty men and thirty women, the first half of them 40-50 years old, and the other half 15-20 years old, were exposed successively for 15 min to four different noises at the same continuous equivalent level LAeq = 75 dB. Auditory brainstem evoked potentials were recorded before and after exposure to each noise. No difference was found between these noises as to their effects upon evoked potentials. After exposure to noise, a significant lengthening of L1, L3 and L5 latencies was observed in men. No significant lengthening was observed in women, although a lengthening of latencies was present in a majority of them. The three latencies, L3 and L5 latencies in particular, were found significantly longer in men than in women. L1 and L5 latencies were significantly more lengthened by noise in men than in women. In both sexes, L5 latencies were found significantly longer in older subjects; the same was true of L3 latencies in male subjects. Noise did not significantly modify intervals between peaks. I-V interval was found significantly longer in older male and female subjects; the same was true of I-III intervals in men. PMID- 7987703 TI - Alleles of the microsomal steroid sulfatase gene (Sts) in the pseudoautosomal region of the heterosomes of the mouse. AB - The gene (Sts) for microsomal steroid sulfatase (STS-EC 3.1.6.2) is located at the distal end of the pseudoautosomal region of the mouse heterosomes. A new improved method was developed to measure the activity of this enzyme in four inbred strains of laboratory mice, their respective congenics for the non pseudoautosomal region of the Y chromosome and their F1s were employed. The method was shown to be highly reliable (.95). No sexual dimorphism was shown but a polymorphism for the enzymatic activity, corresponding to three functional allelic forms was found. The results presented here are compatible with the location of the Sts gene on the X-Y pseudoautosomal region. The underdominance that appears in the F1s, in one set of strains and the difference between reciprocal F1s in the other set must be interpreted cautiously since it is the enzymatic activity which is only measured and not the protein itself. A complex mechanism, involving the gene responsible for the enzyme located on the pseudoautosomal region and autosomal locus or loci which regulate(s) its activity, is suggested as being responsible for the results obtained with the F1s. PMID- 7987704 TI - Speed of skin penetration and initial migration route of infective larvae of Schistosoma haematobium in Meriones unguiculatus. AB - The kinetics of skin penetration of Schistosoma haematobium (Bilharz, 1852) (Trematoda, Schistosomatidae) cercariae is reported for the first time, Meriones unguiculatus (Rodent, Gerbillidae) being used as experimental model. It has been demonstrated that the cercariae cross the epidermis of their hosts either directly or through hair follicles culs-de-sac from 3 to 5 min. The corresponding schistosomulae slide into the superficial part of the dermis or move along the base of hair follicles. Six minutes after, schistosomulae are found in the lumen of lymphatic vessels running alongside blood capillaries. One hour post infestation, the dermis presents acute inflammatory reaction with edema, infiltration of neutrophil and eosinophil leukocytes. Conversely, dilated blood capillaries do not contain any schistosomula. Thus, the initial migration path of infective larvae of S. haematobium in M. unguiculatus is lymphatic. PMID- 7987705 TI - On the relation between phosphate uptake and growth of the cyanobacterium Anacystis nidulans. AB - The energy dependent phosphate uptake by the cyanobacterium Anacystis nidulans has been analysed in terms of a "linear energy converter" that describes the interrelationship between phosphate incorporation into the polyphosphate pool and the photosynthetic proton flux at the thylakoid membrane. It is assumed that both processes are coupled in such a way that uptake proceeds with optimal efficiency at the prevailing phosphate concentration in the growth medium. On the basis of this model two important parameters of the uptake system can be calculated: first, a conductivity coefficient that reflects the activity of the uptake system and second, a minimal threshold value of external phosphate at which uptake ceases. The theoretical data are shown to fit the experimentally observed uptake behaviour of cyanobacteria when the same population is subjected to a transition from growth on low to high phosphate concentrations, mimicking a situation that frequently leads in natural waters to an algal bloom. PMID- 7987706 TI - [Therapy by neutron capture of ocular melanoma: dosimetry and microdosimetry]. AB - Neutron capture therapy (NCT) aims at destroying cancerous cells with the alpha and 7Li particles produced by the neutron capture reaction on 10B. This note reports on the study of the boron distribution in tissues on an animal model (nude mice) xenografted with a human ocular melanoma after an i.p.injection of 2g/kg of 10B-BPA and in cells cultured in the presence of 530 mumol/l of 10B-BPA. A concentration of 64 ppm of 10B in the active part of the tumour with a ratio of concentrations versus the skin of 3.7 are observed. Investigations on cells reveal the presence of boron in the cytoplasm. The biological, dosimetric and microdosimetric consequences of these findings are discussed. PMID- 7987707 TI - [Measurement of nitric oxide and biological systems]. AB - Interest in NO measurement strongly increased with the discovery that NO is endogenously produced by living tissues. This review describes the major techniques for quantification of NO and derivatives in biological models. PMID- 7987708 TI - [Linkage between juvenile glaucoma and chromosome 1q in 2 French families]. AB - Primary open-angle glaucoma is a major cause of irreversible blindness in Western countries for which there is presently no curative treatment. Linkage of hereditary juvenile glaucoma with chromosome 1q21-q23 was recently described in 2 American families. Here we have studied two large French pedigrees with a similar form of familial autosomal dominant juvenile-onset glaucoma. Linkage of glaucoma with chromosome 1 was confirmed in these 2 families. Maximal lod-score of 7.60 was reached at the D1S212 marker for a recombination fraction of 4.4%. The typing of this marker should facilitate the screening of glaucoma families and the identification of individuals at risk for the disease. It will also provide a reference to evaluate the genetic heterogeneity of glaucoma. PMID- 7987709 TI - Phylogeny of decapod cephalopods based on partial 16S rDNA nucleotide sequences. AB - Various systematic and phylogenetic relationships have been proposed for extent decapod Cephalopods, based mainly on morphology and on the rare paleontological remains. Nucleotide sequence data from the 3' end of 16S rDNA gene were used as an alternative approach to morphology; this gene portion having proved to be appropriate to test divergences in other groups of assumed equivalent age. The results from 27 Decapoda species allowed us to calculate phylogenetic trees by the neighbor joining and parsimony methods (Paup and Hennig86). The trees were submitted to bootstrapping. The order Sepioidea, including the sepiids, sepiolids and spirulids, is not supported by molecular evidence. Sepiolids are clearly excluded from the order, and the position of the Spirulidae needs further clarification. In oegopsids, the intrafamilial groupings obtained by the molecular approach is in agreement with morphological data. The unresolved phylogeny at the suprafamilial level might be the result of two different events: earlier divergence than the Cenozoic, or unequal evolutionary rates among taxa having appeared either by successive emergence or by fast radiation. The 3' end of 16S rDNA gene of cephalopods is a precious tool to analyze taxonomic relationships at the infrafamilial level. A gene with a lower evolutionary rate, is necessary to establish higher taxa phylogeny. PMID- 7987710 TI - [Effects of metalloproteinases-1 (TIMP-1) cDNA transfection on biological behaviors of PG cells]. AB - A recombinant plasmid, which contains a full length cDNA of human tissue inhibitor of metalloproteinases-1 (TIMP-1), was constructed by using gene recombinant technique, and introduced into a highly metastatic human giant cell carcinoma (PG) by lipofectin technique. Two of the transfectants, PG-T2 and PG T4, were studied thoroughly. Northern blot showed an increased level of TIMP-1 mRNA in PG-T2 and PG-T4, compared with PG and PG-MV1 (vector-transfected control). The two transfectants also exhibited higher TIMP-1 protein activities. Moreover, they showed significant reduction in their proliferation rate and invasive abilities. The abilities of forming colonies in soft agar and tumorigenecity in athymic nude mice were abrogated in PG-T2 and PG-T4. The preliminary results suggest that a specific upregulation of TIMP-1 expression in metastatic cells could not only suppress their invasive and metastatic phenotype, but also inhibit their proliferation and tumorigenecity. PMID- 7987711 TI - [The metastatic pattern of malignant tumors]. AB - Four hundred autopsy cases of malignant tumors were analysed. Of these 321 cases (80.3%) had carcinoma and 79 (19.7%) sarcoma. In the 79 cases, 65 had malignant lymphoma, and 14 (3.5%) soft tissue and bone tumor. The tumor cells metastatic to the lung and liver were common in the autopsy cases. There were 163 cases of metastatic tumors in the lung and liver respectively (40.5%). The metastatic tumor in the liver was mainly from the breast, large intestinal, ovary, stomach and NHL, and in the lung mainly from the breast, liver, NHL, stomach and ovary. The lymph node metastasis was mainly located in the neck, mediastina, aorta. The extensive metastatic tumors were lung cancer, gastric cancer, breast cancer and NHL, However, carcinoma in uterus cervix, urinary bladder, pharynex and testis was mainly infiltrated in the original region. The tumor metastasis was related to the region, histologic type and differentiation and so on. PMID- 7987712 TI - [Manifestation of abdominal segment of esophagus by body surface ultrasonography and determination of normal values]. AB - Scanning over the oblique section of xiphoid-left costal margin by body surface ultrasonography was adopted in the present study. The esophageal hiatus showed triangle-like strong echo which was called by the author "Hom Dill Casoue". Its dorsal aspect could be confirmed as the abdominal segment of the esophagus. In a general survey of 268 cases of high risk crowd in high incidence area, 82% (217 cases) were manifested clearly. The mean wall thickness was 2.58 +/- 0.54mm, and the mean length 23.7 +/- 5.6mm. Among the 9 cases suspicious of increased thickness, 5 were confirmed to have esophageal lesions. Among them there were 2 cases of esophageal carcinoma, and 2 cases of inflammatory ulcer with edema, and one case of hiatal hernia. The accuracy rate of diagnosis for those with clear manifestation by ultrasonography reached as high as 98% (218/222 cases). This method provides a new measure for the general survey of esophageal diseases in the abdominal segment. PMID- 7987713 TI - [Clinical study on epidermal growth factor and its receptor in human gastric cancer]. AB - We detect the expression of epidermal growth factor (EGF) and epidermal growth factor receptor (EGFR) in 104 specimens of gastric cancer by avidin biotin peroxides complex technique (ABC). The positive rates of EGF, EGFR and synchronous EGF and EGFR were 35.6%, 42.3%, 30.8% respectively. The positive expression of EGF and EGFR to gastric cancer tissue was inclined to occur in patients who were in advanced stages, of poorly-differentiated types, Borrmann III, IV types, scirrhous type, seroinvasive type or lymph node metastasic types. The survival rates at 1, 3, 5 years after gastrectomy in the patients with expression of EGF were significantly lower than the survival rates of the patients with negative expression (P < 0.05). The patients with synchronous expression of EGF and EGFR had the worst prognosis. After gastrectomy, all of them died within 4 years. It is indicated that EGF and EGFR could serve as biological indicators of gastric cancer malignancy and an index for evaluating, the prognosis of the patients with gastric cancer. PMID- 7987714 TI - [Species-specific monoclonal antibodies against Chlamydia pneumoniae]. AB - The purified elementary bodies (EBs) of C. pneumoniae ATCC VR1310 were used for primary immunization of male BALB/c mice (8 weeks of age), with the boost following on day 14. Spleen cells were fused with murine myeloma NS-1 cells on day 24 and hybrid cells were cloned by limiting dilution. Two clones, P17C2 & P33C, secreting species-specific monoclonal antibodies (MAbs) and immunoglobulin IgG2a class were obtained after elimination of those clones that produced antibodies against C. trachomatis L1, L2, A, B, C, E serovars, C. psittaci EAE strain and uninfected BGMK cell antigens. It was showed that the two clones of MAbs reacted with the MOMP 39.5 x 10(3) Da major outer membrane protein of all chlamydia species in Western blot and their ascites titers were more than 1:25 600 in Micro-IF test. PMID- 7987715 TI - [HLA-DQ gene and susceptibility of insulin dependent diabetes mellitus in Chinese population]. AB - Trans-racial analysis of disease association has improved mapping of MHC-linked susceptibility to insulin dependent diabetes mellitus (IDDM). In this study, the contribution of the HLA class II DQA1 and DQB1 genes was investigated. Nine DQA1 and 10 DQB1 sequence-specific oligonucleotide gene probing in 49 IDDM and 48 control subjects from Beijing showed that DQA1-A4 alleles was positively associated with the disease (RR = 11.7, Pc < 0.02) as was the Asp57 negative homozygotes of DQB1 gene (P < 0.01, RR = 5.3), and that Asp57 positive homozygote of DQB1 gene conferred protection against IDDM (P < 0.025, RR = 0.38). Compared with trans-racial study, the decrease of Asp57 negative homozygote frequence and increase of Asp57 positive homozygote frequence in Chinese population may contribute to the low incidence of IDDM. PMID- 7987716 TI - [2 homoharringtonine resistant leukemic cell lines (K562 HHT and L1210 HHT): establishment, characterization and mechanisms of action]. AB - We developed two leukemic cell lines (K562 HHT and L1210 HHT) stably 16.7 fold and 13.4 fold resistant to HHT respectively with which the culture were treated. Both cell lines were also cross-resistant to DOX, VCR, DNR and Mel. Increased expression of MDR1 gene in the both lines was noted. To further evaluate the implications of MDR1 in HHT resistance. We studied the expression of MDR1 in sensitive and HHT-resistant sublines of K562 by ABC with an monoclonal antibody against P170, JSB-1. K562 HHT cells were positive but sensitive cells were negative. Additionally, the increased drug resistance was associated with increased level of expression of alpha and pi class GST gene, but not with increased level of expression of mu class GST gene. PMID- 7987717 TI - [The molecular basis of HLA DR4 alleles associated with rheumatoid arthritis in a Chinese population]. AB - HLA-DR4 gene was studied by polymerase chain reaction method in 95 patients with rheumatoid arthritis(RA) and 130 normal controls in a Shanghai population. The results showed that the DR4 was significantly associated with RA(RR = 3.1, chi 2 = 13.8, P < 0.005). The second exon of DR4 gene was also analysed by PCR-RFLP technique. There were at lest eight DR4 subtypes in this Chinese population. The DRB1 *0405 (Dw15) was the most common allele, accounting for 48% of DR4 positive normal individuals and also is a principal subtype associated with RA susceptibility (RR = 3.1, P < 0.005). Analysis of the third hyperpolymorphic region of DR4 positive samples showed that 92% of patients had a sequence encoding amino acids RRAA or KRAA compared with 56% of the DR4 positive controls (chi 2 = 10.29 P < 0.005). All subtypes that were positively associated with RA susceptibility had the RRAA (DRB1* 0404, 0405. 0408 and 0410) or KRAA (DRB1 * 0401) sequences, while the negatively associated ones (DRB1 0402, 0403 and 0406) had not. As a further evidence, it strongly supported the "shared epitope" hypothesis. The different DR4 subtype structures and frequencies may account for the different associations of DR4 with RA in various ethnic groups. PMID- 7987718 TI - [Molecular biological bases of tumor cell invasiveness and metastasis]. PMID- 7987719 TI - [Prostaglandins and neonatal hypoxia diseases]. PMID- 7987720 TI - Functional anatomy of tendons and ligaments in the distal limbs (manus and pes). AB - Tendons and ligaments of the equine distal limbs have a prominent anatomic, functional, and clinical importance. This article reviews the descriptive and topographic anatomy of these structures in details. Special information is given about the mechanical properties and functional anatomy of the flexor tendons, accessory ligaments, and third interosseous muscle, as well as about their roles during the standing position and gaits. PMID- 7987722 TI - Congenital abnormalities of tendons and ligaments. AB - Congenital deformities of tendons and ligaments are not uncommon in foals. The vast majority of hyperextension deformities are treated successfully with exercise management and extended heel shoes. Successful treatment of contractural deformities depend on the site and severity of the deformity and on the appropriate use of medical, physical, and, possibly, surgical therapy. PMID- 7987721 TI - The pathobiology and repair of tendon and ligament injury. AB - Injury of the collagenous structures comprising tendons and ligaments, either from acute trauma or from repetitive strain lesions, results in protracted periods of disability. The resolution of such injuries often fails to restore the normal morphologic and functional characteristics of the structure and, therefore, either compromises the future performance of the individual or predisposes to an increased risk of recurrent injury. PMID- 7987723 TI - Diagnostic techniques for identification and documentation of tendon and ligament injuries. AB - Conventional clinical examination remains of medical and economic value for diagnosis of soft tissue injuries in the equine athlete. This procedure requires concentration and rigor to establish the diagnosis, and, if possible, some experience to better evaluate the prognosis. None of the new imaging techniques can replace the physical examination, but each may provide additional information. These sophisticated methods are bringing considerable progress in the knowledge of locomotor injuries in the horse and a tremendous improvement in our ability to diagnose precisely lamenesses and limitations of performance. PMID- 7987724 TI - Treatment of superficial digital flexor tendinitis. AB - This article reviews the research and clinical findings relevant to the treatment of acute tendinitis in the horse. The goals of treatment are to reduce inflammation, minimize scar tissue formation, and promote restoration of normal tendon function. A wide variety of treatments have and still are being used to treat tendinitis, which indicates that there is no uniformly successful way to return a horse to full athletic function after injury. Therapy depends on the severity of tendinitis and duration of injury and can be divided into treatment during the inflammatory, repair, and maturation phases of healing. PMID- 7987725 TI - Practical management of superficial digital flexor tendinitis in the performance horse. AB - The authors of this section represent a broad range of practice experience with horses that perform in rigorous and varied sport competitions. Each breed and performance application represent unique challenges of diagnosis and uncompromising demands on rehabilitated tendon injuries. This article will serve to guide, stimulate, and encourage veterinarians to apply scientific criteria to the evaluation of tendinitis therapy in the years to come so that we can arrive at a more valid consensus as to the "best" means of tendon and ligament injury management. PMID- 7987726 TI - Genetics of osteoporosis. PMID- 7987727 TI - Mechanisms of cortical bone loss from the metacarpal following digital amputation. AB - Immobilization bone loss, whether due to whole body immobilization or local causes, is associated with an initial rapid phase of trabecular bone loss, but the long-term effects of immobilization on cortical bone are not well described. We have studied metacarpal morphometry in 16 men who had undergone partial or complete traumatic digital amputations 4-71 years earlier. Noninvolved metacarpals from the affected and unaffected hands were used as controls. Cortical bone width was significantly reduced in the metacarpals proximal to the amputated digits (P = 0.001). In the 7 subjects who suffered amputation before the age of 19, the cortical bone deficit was primarily due to a reduction in the total width of the medullary shaft (P = 0.007), whereas medullary width was not changed. In these subjects the metacarpal was also significantly reduced in length, by a mean 2.9 mm (P = 0.35). In the 9 subjects who had their amputation after the age of 19, both a reduction in total width and an increase in medullary width (P = 0.017) accounted for the cortical bone deficit. The deficit in total width was related to the time since amputation (P = 0.008) and could be accounted for by loss of the normal age-related increase in total width (0.01 mm/year). We conclude that in this model of immobilization osteoporosis, the metacarpal proximal to the amputated digit demonstrates cortical osteopenia.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7987729 TI - Subregion analysis of the rat femur: a sensitive indicator of changes in bone density following treatment with thyroid hormone or bisphosphonates. AB - Measurement of bone mineral density (BMD) by dual X-ray absorptiometry (DXA) is a precise and accurate way to assess changes in BMD due to a variety of causes. However, the degree of bone loss may vary depending on the skeletal site examined. We postulated that interventions that change bone density would have a different effect on an area rich in trabecular bone, such as the distal femur, than on other subregions of the femur. Male Sprague-Dawley rats (325-350 g) were treated with triiodothyronine (T3), a bisphosphonate (pamidronate), or placebo for 21 days and then sacrificed. Ex vivo BMD of the proximal, distal, mid and total femur were measured by DXA. We found that mean BMD of hyperthyroid rats was significantly lower than controls at all femoral subregions. However, the difference in mean BMD between hyperthyroid and control rats was greatest at the distal femur (8.6%). In rats treated with bisphosphonate, mean BMD was significantly higher than controls at the proximal, distal, and total femur. The difference in mean BMD between controls and rats treated with bisphosphonate was greatest at the distal femur (31.8%). Furthermore, pamidronate (APD)-treated rats had lower mean mid-femur BMD than controls. We conclude that changes in BMD after treatment with bisphosphonate or T3 are greatest at the distal femur subregion, and that treatment with bisphosphonate may cause a slight reduction in mid-femur BMD. Future studies examining changes in BMD in the rat femur after interventions that alter mineral metabolism should include subregion analysis. PMID- 7987728 TI - Effect of essential fatty acid deficiency on the fatty acid composition and arachidonic acid levels in rat maxillae and mandibles. AB - The fatty acid composition of total lipids and total phospholipids of maxillae and mandibles of rats fed an essential fatty acid-deficient (EFAD), marginally FAD (MEFAD), and a control diet was determined. Patterns typical of an EFA deficiency such as a decrease in the levels of linoleic acid and archidonic acid along with concomitant increase in the levels of palmitoleic acid, oleic acid, and 5,8,11-eicosatrienoic acid were observed in the EFAD groups. Concentrations of arachidonic acid were significantly lower in total lipids of mandibles and maxillae of rats in the EFAD, but not in the MEFAD rats, than those of the controls. PMID- 7987730 TI - Effect of ultrafilterable fragments from chondroitinase and protease-treated aggrecan on calcium phosphate precipitation in liposomal suspensions. AB - A liposome-centered endogenous precipitation method was used to investigate the effect of ultrafilterable fragments from the enzymatic digestion of rat chondrosarcoma aggrecan on the formation of insoluble calcium phosphate salts in buffered solutions at pH 7.4 and 22 degrees C. Unlike the intact aggrecan and its major chondroitin sulfate and core protein components, disaccharide units from chondroitinase degradation of the aggrecan and small (< 3 kg/mol molecular weight) fragments from protease digestion of the core structure were found to be only weakly inhibitory toward mineral formation. Corresponding reductions in Ca(2+)-binding indicate that these fragments were unable to absorb to active sites on the apatite surface for long enough periods to significantly hinder crystal growth. The data suggest that controlled enzymatic breakdown of aggrecan may be one possible mechanism by which the calcification of growth plate cartilage is allowed to advance in vivo. PMID- 7987731 TI - The loci of mineral in turkey leg tendon as seen by atomic force microscope and electron microscopy. AB - Transmission electron micrographs of fully mineralized turkey leg tendon in cross section show the ultrastructure to be more complex than has been previously described. The mineral is divided into two regions. Needlelike-appearing crystallites fill the extrafibrillar volume whereas only platelike crystallites are found within the fibrils. When the specimen is tilted through a large angle, some of the needlelike-appearing crystallites are replaced by platelets, suggesting that the needlelike crystallites are platelets viewed on edge. If so, these platelets have their broad face roughly parallel to the fibril surface and thereby the fibril axis, where the intrafibrillar platelets are steeply inclined to the fibril axis. The projection of the intrafibrillar platelets is perpendicular to the fibril axis. The extrafibrillar volume is at least 60% of the total, the fibrils occupying 40%. More of the mineral appears to be extrafibrillar than within the fibrils. Micrographs of the mineralized tendon in thickness show both needlelike-appearing and platelet crystallites. Stereoscopic views show that the needlelike-appearing crystallites do not have a preferred orientation. From the two-dimensional Fourier transform of a selected area of the cross-sectional image, the platelike crystallites have an average dimension of 58 nm. The needlelike-appearing crystallites have an average thickness of 7 nm. The maximum length is at least 90 nm. Atomic force microscopy (AFM) of unstained, unmineralized turkey leg tendon shows collagen fibrils very much like shadow replicas of collagen in electron micrographs. AFM images of the mineralized tendon show only an occasional fibril. Mineral crystallites are not visible. Because the collagen is within the fibrils, the extrafibrillar mineral must be embedded in noncollagenous organic matter. When the tissue is demineralized, the collagen fibrils are exposed. The structure as revealed by the two modalities is a composite material in which each component is itself a composite. Determination of the properties of the mineralized tendon from the properties of its elements is more difficult than considering the tendon to be just mineral-filled collagen. PMID- 7987732 TI - Calcium regulating activity of 26,27-dimethyl analog of 24R,25-dihydroxyvitamin D3. AB - To determine the possibility that methyl substitution in 26- and 27-positions of 24R,25-dihydroxyvitamin D3 [24,25(OH)2D3] alters activities of the original compound, the effects of 24,25(OH)2D3 on calcium (Ca) regulating activity were compared with those of its methyl analog [24,25(OH)2(CH3)2D3] in addition to 1 alpha,25-dihydroxyvitamin D3 [1,25(OH)2D3]. 24,25(OH)2D3 at 10(-6) M and 24,25(OH)2(CH3)2D3 at 10(-7) M and above significantly stimulated both bone resorption in neonatal mouse calvaria cultures and formation of osteoclast-like multinucleated cells (MNC) in mouse bone marrow cultures. A stimulative effect of 1,25(OH)2D3 on bone resorption and MNC formation was recognized in very low concentrations (10(-11) M and above). Although a potency of 24,25(OH)2(CH3)2D3 in stimulating bone calcium (Ca) mobilization and intestinal Ca transport was higher than that of 24,25(OH)2D3, the potencies of both compounds were similar to that of 1,25(OH)2D3 unlike in vitro experiments. As 1,24R,25-trihydroxy-26,27 dimethylvitamin D3 showed almost the same effect as 24,25(OH)2(CH3)2D3, the dihydroxy form is suggested to be hydroxylated at 1 alpha position and converted to trihydroxy form in vitamin D-deficient rats. From these results, methyl substitution in 26- and 27-position of 24,25(OH)2D3 was found to elevate Ca regulating activity of the original compound. In addition, it is suggested that the basis for a similarity in potency between 1,25(OH)2D3 and 24,25(OH)2D3 or its dimethyl analog in vitamin D-deficient rats is likely the result of 1 alpha hydroxylation. PMID- 7987733 TI - Androgen resistance and deficiency have different effects on the growing skeleton of the rat. AB - Mature male, female, and androgen-resistant testicular feminized (Tfm) male rats of the same strain were sacrificed at the age of 120 days. Young male and Tfm rats were orchidectomized (orch) at 1 month of age and sacrificed at 120 days. The right femora were dissected, cleaned, defatted, and scanned with the Hologic QDR-1000. Orch and Tfm rats had similar body weights that were intermediate between body weights of their normal male and female littermates. Serum IGF-I concentrations were lowest in Tfm rats; IGF-1 concentrations in orch rats were not lower than in males. Dual-energy X-ray absorptiometry yielded the following results: Total femoral mass and area were lower in female, Tfm rats and in both orch groups compared with intact male rats. Femoral bone density was, however, only decreased in orch rats. Bone density measured in an area containing only cortical bone was not different between groups. However, the density was lower in orch rats in an area containing both cancellous and cortical bone. This finding is consistent with a +/- 50% decrease of cancellous bone volume in orch rats compared with all other groups at the proximal tibial metaphysis (an area containing mainly cancellous bone). These data show that Tfm rats, despite having lower IGF-I levels in serum, low body weight, and decreased femoral areas, manage -in contrast with orchidectomized rats--to maintain similar trabecular bone densities and volumes during growth. We conclude that trabecular bone densities can be preserved in androgen-resistant male rats independent of bone or body growth velocity or IGF-I secretion.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7987734 TI - Calcium cells from snails: response to vitamin D metabolites. AB - Calcium is one of the most important substances affecting the life of molluscs, and vitamin D was shown to be an essential nutrient for land snails. In an attempt to elucidate the role that vitamin D plays in calcium metabolism of land snails, we have developed a procedure for the isolation of specialized calcium cells from digestive gland of land snails, and were able to culture these cells. The effect of vitamin D metabolites on the intracellular exchangeable calcium and alkaline phosphatase activity was studied. The metabolites tested were 25 hydroxycholecalciferol (25(OH)D3), 24,25-dihydroxycholecalciferol (24,25(OH)2D3), 1,25-dihydroxycholecalciferol (1,25(OH)2D3), and the molluscan metabolite E. 25(OH)D3 was found to be the most active sterol in elevating intracellular exchangeable calcium and the activity of alkaline phosphatase, and the molluscan metabolite E was found to be the most potent sterol in the suppression of alkaline phosphatase activity. 1,25(OH)2D3 was shown to suppress both activities at high concentrations, and 24,25(OH)2D3 increased the intracellular exchangeable calcium only at high concentrations. Thus, 25(OH)D3 which is regarded as a storage form of vitamin D and devoid of biological activity, seems to be biologically active in invertebrates. PMID- 7987736 TI - Evaluation of a laser Doppler flowmetry implantable fiber system for determination of threshold thickness for flow detection in bone. AB - Laser Doppler flowmetry (LDF) with the use of a standard metal shafted probe, has been successfully used to study bone blood flow in a wide variety of settings. The use of the standard probe is limited by the requirement that the probe be replaced onto the bone surface or driven into the bone with a trocar. In response to this, a system of implantable, detachable fibers was developed. This system allows repeated measurement over time without repeated surgical manipulation of the area of interest. This study was performed to evaluate the implantable fiber system by determining threshold thickness for flow detection in bone. A flow chamber with perpendicular and end-on flow was designed to collect results under controlled conditions for flow detection. Threshold thickness for bovine cortical and cancellous bone samples was determined after sequentially grinding the specimens and placing them in the flow chamber. A 2% solution of latex circulated in the chamber and each specimen was exposed to both flow directions and both types of probe. The laser Doppler probe was able to detect flow by resting on top of the sample, with the latex on the other side of the sample. The results showed a significantly greater threshold thickness for the standard probes than for the implantable probes, and a significantly greater threshold thickness for trabecular bone than for cortical bone. Despite the reduced threshold thickness with the implantable fiber, this new system was able to consistently detect depth of perfusion of 80-90% of the values for the standard probe.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7987735 TI - Time-dependent effects of parathyroid hormone and prostaglandin E2 on DNA synthesis by periosteal cells from embryonic chick calvaria. AB - Both PGE2 and PTH (1-34) caused a time- and concentration-dependent stimulation of proliferation by embryonic chick periosteal cells. Cells were exposed to the agents for different periods of time, the medium was replaced with fresh medium, and 3H-TdR incorporation was measured after 16 hours. Challenge with 10(-6) M prostaglandin E2 (PGE2) or 10(-7) M parathyroid hormone (1-34) (PTH) for 5 minutes produced 4- and 5.5-fold increases in 3H-TdR incorporation, respectively. Longer exposures, however, produced diminishing responses and after 45 minutes, only minimal effects or slight inhibitions were seen. These time-dependent effects were also seen with forskolin and dibutyryl-cAMP; TPA on the other hand stimulated DNA synthesis after both short- and long-term exposure. Both PGE2 and PTH (1-34) stimulated cAMP synthesis in periosteal cells but neither could be shown to stimulate protein kinase-C (PKC) at concentrations required for stimulation of proliferation, and dibutyryl-cyclic AMP (cAMP) effectively inhibited endogenous PKC activity. It is possible that the stimulation of proliferation by short-term exposure to PGE2 and PTH (1-34) is mediated by cAMP and that the time dependency possibly stems from the inhibition of endogenous PKC activity by increased intracellular cAMP levels. PMID- 7987737 TI - Relationship between bone mineral density of the proximal femur and lumbar spine and quadriceps and hamstrings torque in healthy Japanese subjects. AB - The purpose of this study was to examine the correlations between the muscle torque of the leg extensors (quadriceps femoris) and leg flexors (hamstrings) and the bone mineral density (BMD) of the proximal femur and lumbar spine. To investigate the decline in BMD of proximal femur and lumbar spine, we examined the relative importance of muscle torque, age, and body weight in the prediction of BMD in 340 healthy volunteers (109 males, and 231 females). Age and body weight were independent predictors of femoral BMD in men. Body weight and quadriceps torque were independent predictors of femoral BMD in premenopausal women. Body weight and years after menopause were independent predictors of BMD in postmenopausal women. The BMD was greatly affected by menopause, whereas the muscle torque was independent of the menopause, and showed the negative relationship to age. These results suggest that muscle-building exercise may have the potentiality to elevate the BMD in the proximal femur in premenopausal women. PMID- 7987739 TI - Energy-dispersive X-ray microanalysis of the bone mineral content in human trabecular bone: a comparison with ICPES and neutron activation analysis. AB - To evaluate the accuracy of bone mineral composition determination by electron microprobe analysis (EDX) the measurements have been compared to instrumental neutron activation analysis (INAA) and chemical analysis (ICPES). Bone specimens from five femoral heads were used. The trabecular content of calcium (Ca) and phosphorus (P) was analyzed by the three different methods. The EDX method allows for a microstructural analysis of intact, methylmetacrylate-embedded, undecalcified bone and the measuring points can thus be distinctly identified centrally in each trabecula. The analysis yielded 25.8 +/- 0.7 wt % Ca and 10.5 +/- 0.1 wt % P, compared with 22.2 +/- 0.5 and 23.0 +/- 1.0 wt % Ca, and 9.83 +/- 0.21 and 10.02 +/- 0.44 wt % P for INAA and ICPES, respectively. The EDX analysis was calibrated by consecutive measurements of a hard, pressed tablet of hydroxyapatit of known content. The mean Ca content deviated with -0.38 wt % from the given content and P with -0.89 wt %. We could not verify any particular interference from the embedding procedure, however, it is possible that the relatively lower P content still may reflect this. The magnesium (Mg) concentration was 0.31 +/- 0.02 wt % by EDX and 0.26 +/- 0.02 wt % by INAA. The EDX analytical method provides a useful tool for simultaneous elemental quantification in bone. It has the advantage of permitting the use of regular bone biopsy material and thus allowing for a unique microstructural evaluation of the degree of mineralization.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7987740 TI - Saskatchewan's unique rural public health tradition. PMID- 7987741 TI - Teenage sexuality and sexual health. PMID- 7987738 TI - Selective extractability of noncollagenous proteins from chicken bone. AB - Quantitative analyses of a wide variety of different solvents used for the extraction of several of the noncollagenous proteins of fully mineralized chicken bone powder were carried out to compare both the effectiveness of various procedures and the distribution of specific proteins which were solubilized. Extraction procedures included solutions of 6 M guanidine-HCl, pH 7.0, 0.5 M EDTA, pH 7.4, 0.3 N citric acid, 0.3 N HCl, 0.3 N formic acid, and 0.3 N acetic acid. Chelation of calcium ions by EDTA and dissolution of the mineral phase by acid extraction released 95% or more of the total calcium content of the bone powder by 48 hours, guanidine-HCl released less than 20% or less of the total calcium content even when extraction was carried out by 168 hours. Moreover, although guanidine-HCl solubilized a significant amount of collagen as gelatin, essentially none of the phosphoproteins, osteocalcin, or the proteoglycan decorin were solubilized, as detected by immunological techniques. In contrast, extraction of the mineralized bone powder by HCl and formic acid was very efficient in selectively solubilizing osteocalcin and osteopontin, while bone sialoprotein was selectively released by EDTA, and solubilized to a lesser extent by formic acid. Similarly, EDTA selectively removed decorin compared with HCl, formic, acetic, or citric acids. Only small amounts of osteopontin and osteocalcin were detected in the acetic acid extracts. These results provide methods for the selective solubilization of several different major, noncollagenous proteins from mineralized bone which should significantly aid in maximizing the amount of the specific protein recovered, and the ease with which the various proteins can be purified.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7987742 TI - Prevalence of high risk sexual behaviour in adolescents attending school in a county in Nova Scotia. AB - High school students ina county in Nova Scotia were asked about sexual activity, including high risk practices. Fifty-five per cent had had intercourse, including 82% of those 18 and 19 years of age. Being sexually active was associated with poorer school performance, having parents with less than a university education, being female, and living with other than both parents. Forty per cent of sexually active students had more than one partner in the year before the survey. Thirty five per cent always used condoms for vaginal intercourse. Students having regular intercourse used condoms less, but less frequent condom use was not associated with having fewer sexually partners. Twenty per cent of sexually active students engaged in anal intercourse; 18% of females and 35% of males reporting this practice used condoms for all sexual encounters. Students in this high school population are highly sexually active, and report high risk sexual activities at levels which should be of concern to both public health practitioners and educators. PMID- 7987743 TI - [Important obstacles in the buying of condoms]. AB - This study identifies the most important barriers to buying condoms and their effect on the intention to buy condoms. A total of 99 high school students and 97 members of a physical fitness centre agreed to participate and completed a self administered questionnaire. The most frequently reported barriers are embarrassment (26%), reluctance to be seen (21%), lack of money (16%), and problems of choosing from the available condoms (11%). One quarter of the subjects indicated they would not buy condoms when confronted with any one of these barriers. PMID- 7987744 TI - Unintended and unwanted pregnancy in Halifax: the rate and associated factors. AB - We present the results of a study designed to assess the incidence of unintended and unwanted pregnancies in Halifax, Nova Scotia, and to characterize the socioeconomic and demographic factors associated with women at high risk. Of 200 pregnancies, 32.5% were unintended and 16.5% unwanted. This, together with the rate of therapeutic abortions among Halifax area women, suggests that approximately 45% and 32% of conceptions leading to viable pregnancies are unintended and unwanted, respectively. Contrary to data collected in 1971, the majority of these women were single. Marital status and parity were significant determinants of both pregnancy intention and wantedness. According to these results, unintended and unwanted pregnancies continue to occur at high rates among certain groups of women living in the Halifax region, despite improvements in the efficacy and availability of contraceptives. PMID- 7987745 TI - Canadian national survey of perinatal HIV infection 1991-1992. Canadian Paediatric AIDS Research Group (CPAR). AB - OBJECTIVE: To define the burden of illness and the demographic characteristics of perinatally HIV exposed children in Canada. METHODS: Two national surveys of children born to HIV-infected mothers were conducted. The first survey captured information on all known cases up to March 1991, and the second, additional cases between April 1991 and May 1992. RESULTS: 220 children born to 204 HIV-infected mothers were identified. Quebec cases increased by 20% compared with 33% in Ontario (p < .003) and 50% in the rest of the country (p < .001). Quebec has a higher proportion of black mothers than the rest of Canada (p < .001). Sexual contact continues to be the major risk factor for maternal HIV infection. CONCLUSIONS: This survey confirms a substantial case load and provides an initial demographic profile of diagnosed HIV exposed infants in Canada. PMID- 7987746 TI - Completeness of provincial workers' compensation files to identify fatal occupational injuries. AB - The objective of the study was to ascertain the completeness of Workers' Compensation files to identify fatal occupational injuries. The number of fatalities was counted using two independent sources: the Quebec Workers' Compensation Board (QWCB), and the Coroner's Death Certificates (CDCs), for the years 1987 and 1988. The observed number of cases was 352. The QWCB identified 83.8% of those and CDCs 69.3%. The true number of deaths was estimated, using the capture-recapture methods, to be between 369 and 401. The compensation coverage of work-related fatalities was 66.1% in workers 55 years of age and older and 8.3% in farming occupations. Therefore, Workers' Compensation statistics are inadequate as the single source in these two categories and their exclusive use thus far has led to a failure in recognizing these issues as public health priorities. PMID- 7987747 TI - A health promotion perspective on the House of Commons' report "Foetal Alcohol Syndrome: a Preventable Tragedy". AB - The Ottawa Charter for Health Promotion is used as a conceptual framework to examine the recommendations concerning prevention in the House of Commons' Report "Foetal Alcohol Syndrome: A Preventable Tragedy." Fetal alcohol syndrome cannot be separated from the complex social, physical and economic environments affecting alcohol consumption. For substantial progress to be made in preventing this significant cause of mental handicap, it will be necessary to consider a wide range of preventive actions, beyond public education and mandatory warning labels on alcoholic beverages. A health promotion framework offers a comprehensive, intersectoral approach to this problem. PMID- 7987748 TI - Factors influencing prenatal class attendance among immigrants in Ottawa Carleton. AB - A longitudinal study, examining predictors of infant care behaviours among 283 immigrants in Ottawa-Carleton, included an analysis of factors predicting prenatal class attendance. On bivariate analysis, significant predictors among primiparas included mother's age and education, official language comprehension ability, average number of years resident in Canada, and current immigration status. Using logistic regression analysis, the odds ratio for prenatal class attendance was 7.36 for mothers with excellent or very good official language comprehension compared with mothers who self-rated their ability as fair or poor. Compared with primiparas who were 35 years or older, young mothers (< 25 years) were less likely to have attended prenatal classes (OR = .28) and mothers aged 30 to 34 years were more likely to have attended (OR = 2.22). Among multiparas, maternal age was the only significant predictor of prenatal class attendance. Findings suggest the need for new approaches to prenatal education for immigrant mothers. PMID- 7987749 TI - [The opinion of Quebecois physicians with regard to AIDS]. AB - A mail survey on several medical and social issues surrounding the AIDS epidemic was conducted among Quebec physicians of a random sample. Of 1,530 physicians, 879 (57.5%) returned their completed questionnaire. Results show that the majority of physicians (79.3%) considered AIDS as a priority. A large proportion of physicians (66%) overestimate the occupational risk of contracting HIV following exposure to a contaminated needle. Logistic regression suggests that the perceived risk of contracting HIV through contact with patients is directly related to the physicians' type of medical training and to their estimate of the risk of contamination with a contaminated needle. Finally, a third of the respondents consider continuing medical education on AIDS insufficient in the Province of Quebec while 82.1% want to improve their knowledge about AIDS. PMID- 7987750 TI - Biographical characteristics of injection drug users and behavioural predispositions related to HIV prevention and drug use. AB - OBJECTIVE: This paper presents a preliminary analysis of the determinants of selected behavioural predispositions toward HIV prevention among injection drug users. METHOD: An exploratory factor analysis was used to group attitudinal, behavioural intention and change statements into five predisposing factors and the correlates with these were examined using general linear regression. RESULTS: The analysis demonstrates that many IDUs have responded to AIDS and highlights the characteristics of those who are predisposed to unsafe practices. Predispositions toward safer sex appear to be contextually determined, and needle sharing determined by socio-behavioural history. CONCLUSIONS: The data emphasize the need for prevention programs in educational and correctional systems along with community-wide harm reduction and HIV prevention strategies, especially for younger persons. For older drug users, there may be a need for more intensive rehabilitation programs. Some evidence suggest that greater attention be given to the type of drug dependence when focusing programs. PMID- 7987751 TI - Fatal and non-fatal childhood injuries in Metropolitan Toronto, 1986-1991. AB - The distribution of the cause, rate and nature of fatal and major non-fatal injuries in children living in Metropolitan Toronto and their trends from 1986 to 1991 were systematically reviewed from hospital discharge records and coroner's records. A total of 11,024 non-fatal injuries, of which falls were the leading cause (45%), and 133 fatal injuries, of which intentional injury (21%) was the principal cause, occurred during the six-year study period. The non-fatal injury rate dropped 23%, from 567 to 436 per 100,000 children. Mortality rates also fell during the study period. However, injuries to motor vehicle occupants and drownings increased considerably. Fractures of various kinds were the most common clinical diagnosis. Protecting children in motor vehicles by promoting the use of proper restraints and preventing injuries caused by falls and drowning should be high priorities for childhood injury prevention in Metropolitan Toronto. PMID- 7987752 TI - [Reasons for the hospitalization and length of stay of a homeless population in Montreal]. AB - OBJECTIVE: To compare the hospitalization experience of a homeless population with that of the residents of a low socioeconomic area. METHODS: The homeless hospitalization records (n = 245) were compared with the records of the 3,553 residents of the Departement de Sante Communautaire of Saint-Luc Hospital territory who were admitted to the same hospital. RESULTS: The homeless population is mainly composed of young men. Mental health diagnoses are more frequent while cardiovascular and the obstetrical diagnoses are more rarely seen. Homelessness is associated with an 11.2 increased risk of organic psychosis, a 6.1 risk increase of functional psychosis and a 3.8 risk increase of personality disorders, neurosis and substance abuse. Obstetrical diagnoses are 20 times less frequent among homeless women while the cardiovascular risk did not seem to be affected in our sample. The lengths of stay are similar. PMID- 7987753 TI - Seroprevalence of measles- and rubella-specific antibodies among military recruits, Canada, 1991. AB - A study of the seroprevalence of measles- and rubella-specific antibodies among military recruits in Canada in 1991 was undertaken to: 1) determine the proportion of military recruits who are measles and/or rubella seropositive when they enter the military; 2) detect general problems in the immune coverage in the young adult population; and 3) determine the proportion of measles seronegativity attributable to non-response, waning immunity or lack of exposure to either the disease or the vaccine. One initial blood sample was collected from all 399 recruits enrolled in basic training during the month of January 1991, prior to immunization with measles-mumps-rubella vaccine (MMR). Another sample was obtained from 354 of these recruits 3 to 5 weeks following this immunization. Only 18 (4.5%) recruits had negative measles-specific neutralization on the first sample. Only 12 (3.0%) recruits had negative measles-specific EIA on the first sample. All recruits had neutralization titres 40 or higher on the second sample. A total of 43 (10.8%) individuals had negative results for rubella EIA before immunization, 35 of which (81.4%) tested positive on the second sample. PMID- 7987754 TI - Risk of automobile accidents among elderly drivers with impairments or chronic diseases. AB - A case-control study was conducted in Quebec elderly men in order to document the risk of road accidents associated with impairments or chronic medical conditions. All 1,400 drivers who had had an accident with either mild bodily injury or only property damage during their 70th year in 1988 and 1989 were selected as cases from the accident file of the "Societe de l'Assurance Automobile du Quebec" (SAAQ). They were compared to 2,636 controls randomly selected among drivers of the same age. Information on medical conditions was also obtained for all subjects from the SAAQ. Mileage and driving habits were documented through a mail questionnaire. Relative risk of accidents associated with medical conditions were estimated while controlling for confounders. Overall, the results suggest that elderly drivers of private vehicles with impairments or chronic medical conditions are not at increased risk of road accidents. Only those with arrhythmias had a significant increase in risk (OR = 1.63, CI: 1.00-2.65). This study does not support more severe norms for elderly drivers. PMID- 7987755 TI - Evaluation of the effectiveness of immunization delivery methods. AB - Scientific evidence documenting the effectiveness of immunization delivery methods was summarized using the generic approach developed by the Community Health Practice Guidelines Working Group. The delivery methods examined were those for the adult and childhood vaccines of influenza, pneumococcal infection, hepatitis B, measles-mumps-rubella and diphtheria-pertussis-tetanus-polio. Based on a critical appraisal of 54 eligible comparative studies, the effects of different interventions were obtained and pooled effects were calculated for delivery methods oriented to the client, the provider and the system. The results indicate those interventions found to be most effective for each vaccine. This review of the scientific evidence of the effectiveness of immunization delivery methods provides a base for policy development and assists in the planning of resource allocation. PMID- 7987756 TI - Practice survey of immunization in Canada. AB - A survey was undertaken in September 1991 to document current immunization practice across Canada. Information was obtained during interviews with provincial epidemiologists and key persons involved in immunization programs and recorded on standard data collection forms. Variations in practice are described in five areas: public/private health administration; legislation; monitoring system/coverage rates/surveillance; vaccine management and costs. As changes are being considered to immunization programs, a critical examination of issues such as standardization (in coding, in assessment of waste, in assessment of coverage), surveillance systems and the use of serosurveys would be beneficial. PMID- 7987757 TI - Immunization delivery methods: practice recommendations. AB - Immunization has unequivocally contributed to large-scale reductions in mortality and morbidity due to infectious diseases. In general, consensus on the scheduling of immunizations has been achieved at the national or international level by immunization advisory committees. However, immunization delivery methods are varied and numerous. Although specific methods have been proposed, compared and evaluated, the available evidence has not been comprehensively summarized for informed public health action. This paper integrates evidence based on scientific documentation, a Canada-wide practice survey and expert opinion to formulate practice recommendations for immunization delivery methods and to identify areas for further research. PMID- 7987758 TI - Partner notification for sexually transmitted diseases: an overview of the evidence. AB - OBJECTIVE: To compare the effectiveness of alternative partner notification strategies for gonorrhea, chlamydia, syphilis, HIV and hepatitis B. DATA SOURCES: Studies were identified using MEDLINE, EMBASE, SCISEARCH and other databases, review of reference lists and personal contact with over 80 international experts. STUDY SELECTION: Studies with at least two comparison groups exposed to different partner notification strategies were included. DATA EXTRACTION: Methodological rigor was assessed, and information regarding study populations, interventions and outcomes was extracted independently by two reviewers. MAIN RESULTS: Twelve studies met our inclusion criteria; five were methodologically strong; seven provided data on the referral process; four provided data on trained interviewers compared with routine care providers; and three provided data on the interview process. CONCLUSIONS: Only limited, broad conclusions regarding the effectiveness of various partner notification approaches could be drawn from these comparative studies. Until newer data become available, practice guidelines must be based to a large extent on other grounds. PMID- 7987759 TI - A survey of public health partner notification for sexually transmitted diseases in Canada. AB - OBJECTIVE: To describe the range of practice for sexually transmitted disease (STD) contact tracing/partner notification (PN) by public health agencies in Canada. METHODS: A two-level mailed survey, using two different questionnaires, was conducted from Aug. 1991 to Feb. 1992, directed to: 1) provincial and territorial epidemiologists/directors of STD control, asking about program organization; and 2) 154 local health units/provincially run PN programs, asking about practice patterns of STD partner notification. CONCLUSIONS: In Canada, STD PN by public health agencies is routinely practised in most provinces. PN efforts vary by the STD; less PN effort goes to chlamydia despite a high burden of illness; HIV PN is frequently perceived to be within the responsibility of the physician. For STDs with higher PN effort, the preferred method is provider referral. Targeting is seldom utilized, and there are little available data at a local level monitoring even process measures of effectiveness. PMID- 7987760 TI - Partner notification for sexually transmitted diseases: proposed practice guidelines. AB - Using the results of an analysis of available scientific evidence and a survey of current practice in Canada, as well as expert opinion, these guidelines attempt to consider current partner notification practice in Canada and recommend an approach to determining practice which is flexible enough to address local circumstances. Priority areas for future research were also identified. PMID- 7987761 TI - The evaluation of the effectiveness of routine restaurant inspections and education of food handlers: critical appraisal of the literature. AB - Literature databases were scanned to locate articles pertaining to food handler education and restaurant inspection. Papers which met pre-established criteria, as described in the generic protocol produced by the Community Health Practice Guidelines Project (CHPG), were evaluated by standardized consideration of criteria. Studies were rated on a scale of one to three. There were eight papers related to the intervention of education, four papers dealing with the intervention of restaurant inspection, and one pertaining to both. the evidence presented in the papers regarding the effectiveness of food handler training in improving food establishment sanitation was weak, but it appeared that some training resulted in improved inspection scores. It appeared that inspections were beneficial, although it was not clear whether three or more inspections were better than two. No inspections appeared to result in worse inspection scores. PMID- 7987762 TI - The evaluation of the effectiveness of routine restaurant inspections and education of food handlers: restaurant inspection survey. AB - To determine restaurant inspection and food handler education practices in Canada, a survey of 141 jurisdictions was conducted. The response rate was 100%. All jurisdictions inspected restaurants, but the frequency of routine inspection varied from none to six or more times per year. The frequency of violations found on routine inspection was associated with foodborne illness. However, the frequency of inspection was not correlated with disease or with violations. Food handler education courses were mandatory in 32% of jurisdictions. Most courses were one to two days. No correlation was found between the numbers of individuals trained in the past year and violations or reported foodborne disease. This lack of reduction in reported foodborne illness may be due to the ecological nature of the survey or to the lack of effectiveness of food handler education or of routine restaurant inspections in reducing violations. PMID- 7987763 TI - Routine restaurant inspections and education of food handlers: recommendations based on critical appraisal of the literature and survey of Canadian jurisdictions on restaurant inspections and education of food handlers. AB - Inspection of restaurants and education of food handlers are two methods used by regulatory agencies to ensure food served in restaurants is safe to eat. The variation which exists in the implementation of these programs suggests that the programs' effectiveness is lacking or is not clear. Recommendations based on the Community Health Practice Guideline methodology, the results of a critical review of the literature, the results of a survey of practices, and expert opinion were developed. The recommendations include: continuation of routine inspections at a frequency of one to two inspections per year per restaurant and the continuation of education programs. The evidence on which these recommendations are based is scant and more research is needed to ensure programs are needed, effective and efficient. PMID- 7987764 TI - An approach to the development of practice guidelines for community health interventions. AB - The Community Health Practice Guidelines (CHPG) project was initiated to develop a systematic approach to the critical evaluation of evidence on the effectiveness and efficiency of community health interventions and to the formulation of evidence-based practice recommendations. Three community health interventions- immunization delivery methods, partner notification for sexually transmitted diseases and the combination of restaurant inspection and education of food handlers--were used as prototypes to develop a standardized approach. The CHPG process consists of three components: a review of scientific evidence, a practice survey and formulation of practice guidelines. Imperatives for further development of the CHPG and define research priorities process include creating a coalition of public health organizations to sponsor the process and refining the consensus process so that the practice guidelines accurately reflect both the scientific basis of public health practice and the values of those affected. PMID- 7987765 TI - Future of child psychiatry. PMID- 7987766 TI - Future of child psychiatry. I: Models and guiding principles. AB - This article reviews some concepts the author believes will guide scientific and clinical work in child psychiatry during the next 25 years. Specifically, it is postulated that the traditional biopsychosocial model may have to be expanded to look at ways we can understand transactional events versus nonshared family characteristics, the development of internal representations and risk factors versus risk carriers. PMID- 7987767 TI - Future of child psychiatry. II: A personal perspective. AB - This paper provides an overview of key future directions that child psychiatry may follow. It then focuses on the potential value of longitudinal studies in general and on those involving attention deficit hyperactive disorder in particular, with the aim of delineating how such studies may enable us to proceed toward some of the future directions outlined. PMID- 7987768 TI - The borderline family in the borderline child--understanding and managing the noise. AB - This paper demonstrates the particular functions of noise communication in a borderline child and family. Analysis shows noise to have a primary role for the individuals and the family in protecting self, promoting attachment, defending against the experience of emptiness and depletion and communicating lack of attunement. Treatment objectives were to foster the development of a more differentiated and cohesive self for the individuals and the family. PMID- 7987769 TI - Psychiatric disorders of children "in care": methodology and demographic correlates. AB - This paper examines psychiatric symptoms and disorders in children in the care of a Children's Aid Society. Youth, caretaker and teacher scores on the Standardized Clinical Information System questionnaire were correlated with demographic and maltreatment data gathered from the files of children from a Children's Aid Society. Mean externalizing and internalizing scores for the study group were significantly elevated above the norm on the youth, caretaker and teacher reports; externalizing more so than internalizing. Forty-one percent to 63% of the children studied scored in the pathological range for one or more disorders. Conduct disorder was the most common disorder (30% to 50%). Within the study sample, temporary wards and children with a history of having been abused had more elevated scores. The authors conclude that children in foster care have significant psychiatric morbidity reflective of the extreme adversity and maltreatment they have experienced. PMID- 7987770 TI - Familial risk factors associated with intrafamilial and extrafamilial sexual abuse of three to five year old girls. AB - This study intended to identify familial risk factors which differentiate sexually abused young girls from nonabused girls and, further, young victims of intrafamilial from those of extrafamilial sexual abuse. The subjects were 112 girls aged three to five years and their families. Forty-two were the victims of intrafamilial sexual abuse and 28 were victims of extrafamilial sexual abuse while 42 girls were not the victims of abuse. The three groups of girls were matched for age. Comparisons indicated that the families of abused girls had less harmony and stability in the marital unit and were headed by less competent parents. Mothers in both abuse groups were significantly more likely to have experienced sexual abuse as children. For all comparisons, the intrafamilial group showed greater disadvantage and dysfunction than the extrafamilial group. The intrafamilial group was differentiated from the extrafamilial group by worse spousal relationships, inadequate boundaries in parent-child behaviour, father's history of physical abuse as a child and violent behaviour as an adult and maternal disapproval of the child victim. These findings suggest that child sexual abuse is related to a longstanding collection of interconnected adult personal and relational deficiencies which result in inadequate parenting for the young victim. PMID- 7987771 TI - The relationship between life events during adolescence and affect and personality functioning. AB - Bowlby's concept of the internal working model is useful in conceptualizing how a child develops a sense of self and security through the availability of significant relationships. The lack of secure attachments may lead to dysphoric moods and poor personality functioning. We have shown that a proportion of teenagers develop dysphoria as well as personality disturbance during adolescence. A study sample of 59 youths was examined at early, middle and late adolescence. Ratings were made of affect, attitudes and personality functions. At the same time, information was obtained about family status and functioning. Results showed that certain family and life events were more strongly correlated with changes in affect in early adolescence. These affects were both internalized and externalized. Middle adolescence appeared to be quiescent, without any correlations with affect or personality problems. In late adolescence, there were correlations between family changes and personality dysfunction as well as dysphoria. This shows that family changes which threaten the availability of significant attachment figures are linked to emotional and behavioural disturbance in early adolescence and personality and emotional disturbance in late adolescence. PMID- 7987772 TI - Factors associated with dropout from group psychotherapy with depressed adolescents. AB - Attempts to determine the characteristics of those individuals who drop out from psychotherapy have yielded few consistent findings. Clinically depressed adolescents who completed a course of brief group therapy were compared with those who failed to complete treatment. Although no differences were found on a number of clinical and demographic variables, those who dropped out were more likely to be one grade behind in school and to have a history of alcohol and/or drug abuse. The implications of these findings for research and practice are discussed. PMID- 7987773 TI - Long term outcome of an attachment-based program for conduct disorder. AB - There is increasing concern among professionals and the public about the level of violence and antisocial behaviour among our youth. This has been coupled with confusion and a sense of helplessness about which types of interventions are most effective in responding to these difficulties. Some professionals and advocacy groups are calling for tougher disciplinary responses to violence and antisocial behaviour, including changes in the Young Offenders Act. Yet, such interventions are rarely effective in producing the desired reductions in these behaviours. Other professionals have called for better forms of treatment. However, few treatments have been shown to be effective in bringing about long term reductions either in aggressive behaviour or in the concomitant psychological difficulties experienced by these youths. In this paper, a description is presented of an approach to understanding conduct disorder that focuses on attachment as an organizing principle of behaviour and affect. Also, a description is presented of a community-oriented program that is based on attachment theory, as well as the results of the program evaluation at six, 12 and 18 months following discharge. The findings replicate and extend earlier findings reported by Holland et al (1) on the effectiveness of this approach. PMID- 7987774 TI - Iron deficiency in two adolescents with conduct, dysthymic and movement disorders. AB - Enquiry into a marginally subnormal hemogram in two adolescents with complex conduct, dysthymic and movement disorders uncovered a striking iron deficiency and prompted a trial of replacing psychotropic medication with iron therapy. The rationale of iron therapy for behavioural disturbance was examined from the clinical, neurochemical and psychopharmacological points of view. Although further study is required to confirm the therapeutic efficacy and to define the precise nature of iron deficiency in conduct disorder, the weight of the evidence suggests that correcting the nutrient deficit may be an essential step toward a refinement of therapeutic strategies. The presence of a borderline hemogram, hypermenorrhea and malnutrition should alert clinicians to the possibility of iron deficiency, and laboratory screening for hypoferremia should be considered when assessing conduct disorder. PMID- 7987775 TI - Re: A scoring error in the Mini-Mental State Test. PMID- 7987776 TI - Re: A scoring error in the Mini-Mental State Test. PMID- 7987777 TI - Re: A scoring error in the Mini-Mental State Test. PMID- 7987778 TI - Re: Homicide followed by suicide. PMID- 7987779 TI - Caring for refugees in a mental hospital. PMID- 7987780 TI - The treatment of depression with group behavioural-cognitive therapy and imipramine. AB - Twenty-four outpatients meeting DSM-III-R criteria for major depression were assigned to group behavioral-cognitive therapy either with or without antidepressant medication (imipramine). Eighteen patients completed 15 weekly sessions of treatment. Equivalent improvement was observed in both regimens after treatment. The results essentially maintained at six months follow-up. This suggests that a group format of behavioural-cognitive therapy is a viable therapeutic intervention for outpatients diagnosed as suffering from major depression. However, the addition of imipramine to group behavioural-cognitive therapy did not enhance the outcome. PMID- 7987781 TI - Personality disorder in the elderly depressed. AB - The objectives of this study were to examine the association of personality disorder with outcome of depression in older patients (age > or = 60) treated in a psychiatric day hospital for depression and to compare the clinical diagnosis of personality disorder at admission with the results of a semi-structured interview at follow-up. Sixty-four patients were followed up for a mean interval of 30 (13-49) months after admission to the psychiatric day hospital and the semi structured interview, Social Support Scale, Life Events Inventory, Hamilton Depression Rating Scale and Mini-Mental State Examination administered by a psychiatrist blind to the details of the index admission. Forty-nine informants (a close friend or relative) were also interviewed using the semi-structured interview. Axis II diagnoses at the time of admission were determined from patient records. Personality disorder diagnoses were analysed according to DSM III-R clusters. Twenty-one (33%) patients fulfilled criteria for personality disorder at admission and 23 (36%) at follow-up. There was strong agreement (k = 0.78) between patient and informant semi-structured interview results and moderate agreement (k = 0.41) between diagnosis at admission and at follow-up. Presence of a personality disorder, and in particular a cluster B personality disorder diagnosis was associated with chronic outcome of depression and with impaired social support. Personality is a significant factor in the outcome of depression in the elderly. It remains unclear whether current methods of assessment tap enduring characteristics, or manifestations of affective state. PMID- 7987782 TI - [Positive and negative symptoms in schizophrenia: a current overview]. AB - The purpose of this article is to summarize the results of studies examining the validity of the positive and negative sub-types of schizophrenia as proposed by Crow. The authors summarized Crow's model's predictions in the form of 12 research questions and examined whether its predictions were confirmed. The following predictions are generally confirmed by the data collected: (i) it is possible to measure negative symptoms with accuracy; (ii) the negative symptoms predict a deterioration; (iii) the negative symptoms are generally correlated with overall cognitive deficits; (iv) each dimension appears to have distinct neurobiological substrata. However, several elements of the Crow model are not supported by the data collected. Among the necessary modifications, the most important are as follows: (i) it appears more productive to conceive of the negative symptoms as distinct dimensions, rather than distinct diseases; (ii) at least three dimensions exist for describing the symptoms of schizophrenia; (iii) the negative symptoms are not necessarily intrinsic to the schizophrenic process, and they may be due to other causes; (iv) the negative symptoms are not necessarily irreversible, and can be improved under ataractics; (v) the positive symptoms, in particular those relating to disorganization, can also be correlated with cognitive deficits. PMID- 7987783 TI - Continuity of care for conduct disordered youth. AB - The objectives of this study were to determine which risk factors associated with chronicity had been displayed by youths who had been treated for conduct disorder in a tertiary level mental health centre and also to count the number of interventions and the number of agencies involved during their many years in treatment. The files of 25 youths with conduct disorder were examined to extract all relevant data. The youths averaged nine years between first intervention and last discharge. Common risk factors were the early onset and the variety of antisocial behaviours and the multiple settings in which behaviours occurred. The youths experienced an average of 19 interventions by 15 agencies. Interventions lasted on average seven months with little occurrence of follow-up. The severity of antisocial behaviours increased from first to last intervention. The apparent ineffectiveness of treatment may be related to the short duration of treatments and the lack of follow-up which resulted in the involvement of many agencies. PMID- 7987784 TI - [Sexuality in the psychiatric milieu]. AB - The main goal of this paper is to describe the problems associated with the expression of sexuality of patients in a psychiatric setting. The problem is analyzed according to the normalization principle. The staff's attitude is considered to be a determining factor in this situation. The authors present the principal conclusions of their study and make some practical recommendations. PMID- 7987786 TI - Legally untreatable--a new category of long stay patient? AB - The case is presented of a young and violent chronic schizophrenic patient whose symptoms respond to antipsychotic medication but who was recorded, at a time when he was deemed competent, as expressing a wish that he should not be given antipsychotic treatment. Under the present usage of the Ontario Mental Health Act, substitute consent givers are bound by such a "prior competent wish" and this patient must now be considered one of a growing group of "legally untreatable" psychotic patients. PMID- 7987785 TI - Agenesis of corpus callosum and dementia of the Alzheimer's type: a review and case report. AB - This paper describes a previously sufficiently functioning 57 year old man who presented with a recent onset of frontal behaviour. Partial agenesis of corpus callosum was an incidental finding on a computerized tomography scan. The EEG was within normal limits and neuropsychological testing did not reveal any interhemispheric disconnection. A SPECT-Scan revealed bilateral hypoperfusion, consistent with Alzheimer's dementia. Normal functioning up to 50 years of age and a later manifestation of Alzheimer's disease along with agenesis of carpus callosum is of clinical interest as such an association has not been published. PMID- 7987787 TI - The effect of testosterone on psychopathology and sexual function in a paranoid schizophrenic self-castrate. AB - It has been suggested that the administration of androgens to paranoid schizophrenics who castrate themselves because of religious delusions and sexual guilt might exacerbate the psychosis and increase the risk of further self mutilation. We administered testosterone enanthate to such a case intermittently during his 12 week hospital stay and studied simultaneously, psychopathology (Brief Psychiatric Rating Scale and clinical assessment), hormone levels and sexual behaviours. Sexual behaviours increased in line with increased serum testosterone levels; psychopathology declined. Following his discharge, he was managed on a regime of phenothiazines and monthly testosterone injections. After one year, he was enjoying normal heterosexual activities (without guilt) although his extreme religiosity had not declined. PMID- 7987788 TI - Delayed onset post-traumatic stress disorder in World War II veterans. AB - Delayed onset post-traumatic stress disorder is an underreported condition in World War II veterans. There is little agreement about the etiology of this syndrome. Two cases of post-traumatic stress disorder in World War II veterans whose individual onset was delayed for over 30 years are described. These veterans developed the symptoms associated with the stresses of late life including bereavement, social isolation and chronic medical illness. Theories regarding the etiology of this syndrome are reviewed and a hypothesis suggesting a heterogeneous condition is presented. PMID- 7987789 TI - Multiple personality: a psychiatric misadventure. AB - Though multiple personality disorder has been diagnosed with increasing frequency over the past decade, its validity has been called into question. A brief review of the literature indicates a likelihood of socio-cultural influences and iatrogenicity in many if not most cases. Symptoms of multiple personality disorder parallel other psychiatric syndromes but are usually given diagnostic priority. The author has described five cases diagnosed multiple personality disorder by another health professional in which iatrogenic influences are clearly evident. All renounced both the diagnosis and the alleged sex abuse etiology. The patients possess insight into the role their attachment and dependency on their former therapist played in the development of their apparent multiple personality disorder. PMID- 7987790 TI - Psychosis associated with lobar holoprosencephaly. PMID- 7987791 TI - Frequency and nature of calls received on the distress line of a chapter of Ontario Friends of Schizophrenics. PMID- 7987792 TI - Treatment of dysthymia with sertraline. PMID- 7987793 TI - Rapid tranquilization with intramuscular clonazepam. PMID- 7987795 TI - Appreciation of the significance of cytogenetic and FISH analysis of bone marrow in clinical oncology. AB - Due to some empiric reasons, bone marrow (BM) has never been emphasized and appreciated as a valuable alternative source for metaphases of tumor nature. In the present study, we report the cytogenetic and fluorescence in situ hybridization (FISH) studies of BM in 172 patients with various tumors. Our results indicate that cytogenetic and FISH analyses of BM provide a valuable biologic approach concerning the diagnosis of tumors, evaluation of metastasis, and assessment of secondary hematologic malignancies. Thus, we suggest strongly that these studies become a standard part of clinical pathologic investigations in dealing with clinical oncology. PMID- 7987794 TI - Detection of i(17q) chromosome by fluorescent in situ hybridization (FISH) with interphase nuclei in medulloblastoma. AB - Medulloblastomas are the most frequent primitive neurectodermal tumors in children. An isochromosome for the long arm of 17, i(17q), is found in 30% of medulloblastomas. For some authors, this abnormality is observed in cases with a shorter survival time. In our cytogenetic studies of 30 medulloblastomas, we observed i(17q) in only three cases, a monosomy 17 in two cases, a monosomy 22 in four cases, nonspecific numerical or structural abnormalities in five cases, and normal karyotypes in 12 cases. We compared the results of karyotypic analysis after culture and FISH with a chromosome 17 alpha satellite DNA probe on interphase nuclei in five cases of medulloblastoma. In one case, i(17q) was only observed in four cells in karyotypic analysis, in three cases a normal karyotype was found, and in one case karyotypic analysis was impossible. In all of these cases, i(17q) was observed in a great number of nuclei by FISH on interphase nuclei. Our study shows that the FISH on interphase nuclei permitted us to observe i(17q) in the cases where it was not or could not be completely detected by karyotypic analysis. The association of these two techniques is required to detect i(17q), an abnormality whose prognosis value in medulloblastomas is now recognized. PMID- 7987796 TI - Cytogenetic biclonality corresponding to multiphasic differentiation in an atypical thyroid adenoma. AB - Cytogenetic aberrations have been described in about 30% of benign thyroid tumors, but their role for tumorigenesis or progression has not yet been elucidated. We describe the cytogenetic analyses in a thyroid adenoma with two different clonal cytogenetic stemlines: 45,XX,der(1)t(1;14)(p13;q11.2 q(13),t(5;12)(q11.2;q24),del(9)(q12),- 10,der(11)t(11;?;19)(p15;q13),der(14)t(14;15)(q11.2-q13;q23),del(15)(q23 ), der(15)t(9;15)(q12;p10),der(19)t(10;19)(q11.2;q13)/46,X,?inv(x),?inv(3) (p21q29),t(3;8)(q26;q12). Histologic examination revealed an atypical follicular thyroid adenoma containing microfollicular, follicular, trabecular-solid, and oncocytic components. There may be a direct relation between the different cytogenetic stemlines and the histologic diversity of the tumor. Thyroid tumors with complex karyotypes involving the 19q13 breakpoint may represent advanced stages of karyotypic evolution and therefore warrant an extensive clinical follow up. PMID- 7987797 TI - A single clonal abnormality of chromosome 1 found in an adenocarcinoma of the uterus. AB - Adenocarcinomas usually have a complex genome comprised of multiple chromosomal alterations. These neoplasms rarely express a single genomic change. We report the first case of an endometrial adenocarcinoma demonstrating a single genomic variation in chromosome 1 associated with a 2 1/2-year survival. The finding of this anomaly may be important in determining the etiology and clinical behavior of uterine malignancies. PMID- 7987798 TI - Reassessment of an apparent t(12;17)(p11;p11) as an unbalanced t(17;21)(p11;q11) in a case of B-cell chronic lymphocytic leukemia by fluorescence in situ hybridization. AB - We report a published case of chronic lymphocytic leukemia (CLL) in which conventional cytogenetic analysis supported the presence of an unbalanced t(12;17)(p11;p11). However, fluorescence in situ hybridization (FISH) analysis, with specific DNA libraries from chromosomes 17 and 21 (chromosome painting), demonstrated that the translocation was actually an unbalanced t(17;21)(p11;q11). PMID- 7987799 TI - Isochromosome 17q- in acute promyelocytic leukemia. Molecular characterization by fluorescence in situ hybridization. PMID- 7987800 TI - Recurrent chromosome abnormalities in peripheral T-cell lymphomas. AB - Cytogenetic findings in 45 cases of peripheral T-cell lymphomas (PTL) diagnosed according to the updated Kiel classification are reported. Recurrent numerical chromosome aberrations comprised -X, -Y, -13, +X, +3, +5 and +7. Recurrent structural aberrations included t/del(1)(p31-32), t(2;5)(p23;q35), dup(5)(q23q31 32), t/dup(6q), t/del(6q), trisomy 7q, and trisomy 8q, mostly due to i(8)(q10), and changes in 14q11 and 14q32.1, mostly due to inv(14)(q11q32.1), t/del(13)(q14), t(6;7)(q13;q13), and t(13;17)(q11-13;p11). All deletions in 6q involved band 6q21 and all partial trisomies of 7q led to an amplification of band 7q21. Further studies are needed to ascertain whether these cytogenetic findings in PTL are of clinical and prognostic significance. PMID- 7987801 TI - B-cell acute lymphoblastic leukemia with L1 morphology and coexistence of t(1;19) and t(14;18) chromosome translocations. AB - We report a case of adult de novo acute lymphoblastic leukemia (ALL) with unique cytogenetic abnormalities and discrepant morphologic and immunologic features. Morphology was L1 by the French-American-British classification, but flow cytometry was consistent with a mature B-cell phenotype. Cytogenetic analysis showed numerous chromosome abnormalities nonspecific for lymphoid neoplasm except for t(1;19) and t(14;18). The former is characteristic of pre-B-ALL and the latter is characteristic of follicular lymphoma. This is the first report of these two translocations occurring concurrently in ALL. PMID- 7987802 TI - Multiple karyotypic abnormalities in three cases of small cell variant of T-cell prolymphocytic leukemia. AB - Cytogenetic, clinical, and laboratory findings of three patients with a small cell variant of T-cell prolymphocytic leukemia (T-PLL) are presented. Immunophenotypic studies of the morphologically typical small cell variant prolymphocytes showed a mature helper T-cell phenotype (CD4+CD8-) in one patient and a common thymocyte phenotype (CD4+ CD8+) in two other patients. The cytogenetic analysis revealed complex karyotypes with several structural aberrations in the peripheral blood lymphocytes of all three patients. In all cases chromosome 14 was affected with the breakpoint at 14q11. Inversion (14) and isochromosome 8q, often reported as an additional aberration in T-PLL, were detected in two of the patients. In two patients a translocation of the short arm of chromosome 12 was also seen. The T-cell receptor beta-chain gene showed a clonal rearrangement in all three patients, whereas no rearrangements were detected in the immunoglobulin genes. The survival of the patients ranged from 10 weeks to 48 months. The association between cytogenetic, clinical, and laboratory data is discussed. PMID- 7987803 TI - Association of abnormalities of chromosome 11 with t(14;18) in diffuse non Hodgkin's lymphoma. AB - Cytogenetic studies of non-Hodgkin's lymphomas (NHL) have revealed a nonrandom translocation, t(14;18)(q32;q21), to be strongly correlated with follicular histology. In our recent study of 149 cases of NHL, 68 cases had a t(14;18). Forty-four of these were follicular and 24 diffuse. In the majority of cases (90%) there were additional chromosome abnormalities, which were analyzed to determine whether any were specifically associated with diffuse histology. Chromosome 11 abnormalities occurring together with the t(14;18) were found to be present in 17/68 cases; 14/17 (82%) were diffuse and 3/17 (18%) were follicular NHL. Thus, 14/24 (58%) of all diffuse lymphomas with t(14;18) had an abnormality of chromosome 11 compared to only 3/44 (7%) of follicular lymphomas, suggesting that the addition of an abnormality of chromosome 11 to a t(14;18) karyotype is associated with diffuse histology. PMID- 7987804 TI - Hypomethylated status, but not RAG-1, is required for T-cell receptor-beta-chain gene rearrangement in acute leukemia cells. AB - We studied the relation between the level of recombinase activating gene (RAG-1) and the methylation status of T-cell receptor (TCR)-beta-chain gene in TCR-beta rearrangement in acute leukemias, including 21 patients with B-precursor acute lymphoblastic leukemia (ALL) and 23 with acute myeloid leukemia (AML). The rearrangement of the TCR beta-chain gene in acute leukemia always occurs at the allele that contains hypomethylated cytosine-cytosine- guanine-guanine (CCGG) sequences within either the TCR-J beta 1 or TCR-J beta 2 regions. Moreover, all B precursor ALL patients with TCR-beta rearrangement had hypomethylated TCR-beta with or without the presence of RAG-1 activity detectable by reverse transcript polymerase chain reaction, whereas none of the AML patients with TCR-beta rearrangement and hypomethylated TCR-beta had detectable RAG-1 activity. Some ALL patients had hypomethylated TCR-beta and RAG-1 activity without TCR-beta rearrangement, and most of them showed t(4;11)(q21;q23) or t(9;22)(q34;q11). These results indicate a correlation between the hypomethylation status of the TCR-beta and its rearrangements, but some unknown blockage factor for this association exists in B-precursor ALL patients with specific chromosomal translocations. PMID- 7987805 TI - Chromosome abnormalities in meningeal neoplasms: do they correlate with histology? AB - Thirty-three meningeal neoplasms were karyotyped, and the results were compared with histologic features. Thirteen neoplasms had no discernible abnormality or sex chromosome loss only; nine had monosomy or structural abnormality involving only chromosome 22; and 11 had other chromosome abnormalities with or without chromosome 22 involvement. Histologic evidence of invasion was not associated with an abnormal karyotype in the three angioblastic tumors examined. All seven fibroblastic meningiomas had abnormal karyotypes, with monosomy 22 the most common change. Abnormal karyotypes were detected in 76% of syncytial and 55% of transitional meningiomas. When these results were combined with those from 259 meningeal tumors reported since 1987, abnormal karyotypes were detected in at least half of all histologic types. Chromosome changes secondary to those involving chromosome 22 may indicate additional areas of the genome that play a role in tumor progression. In the combined series, chromosome losses were most frequently observed in meningiomatous and transitional histologies; chromosomes 1, 6, 14, 18, and Y each were lost in 10 or more meningiomas, whereas only chromosome 20 was gained at the same frequency. Structural abnormalities most frequently involved chromosome 1. These changes are distinctly different from those observed in other common intracranial neoplasms, specifically astrocytic neoplasms. PMID- 7987806 TI - Aneuploidy for chromosome 1 and overall DNA content in benign and malignant breast disease. AB - Fluorescence in situ hybridization (FISH) with a probe for the pericentromeric region of chromosome 1 and DNA content measurements by image-analysis-based densitometry have been carried out on imprints of benign and malignant breast tissue. In general, an increase in the number of spots per nucleus was observed in the invasive carcinomas, with a large intercellular variation. In comparison with lymphocytes from controls, some cases of benign breast disease already had an increased frequency of aneusomy of chromosome 1, although they were all (near)diploid by DNA-content. However, an overall concordance between the DNA content measurements and the results of FISH was observed, although some exceptions were seen. A statistically significant correlation between the DNA index and the mean number of spots for chromosome 1 per nucleus was found. A linear discriminant analysis was applied on the data; the resulting classification of patients was most accurate when parameters describing DNA content and FISH results were combined. PMID- 7987807 TI - Telomere shortening in leukemic cells is related to their genetic alterations but not replicative capability. AB - We compared telomere length in donor leukemic cells and corresponding established cell lines from three patients with chronic myeloid leukemia (CML) and three with acute lymphoblastic leukemia (ALL) to study the relation between the immortalization capacity of hematologic neoplasms and telomere length. Six of the seven established leukemia cell lines (four CML and two ALL) carried additional chromosome changes and had shorter telomere repeats than those of the donor patients' leukemic cells; the remaining ALL line showed no significant difference in telomere length between fresh leukemic cells and the corresponding cell line. Thus, most established leukemic cells lose effective telomerase activity during the process of establishment, and reduction in telomere length of established leukemic cells appeared to be associated with the presence of additional chromosome changes. PMID- 7987808 TI - Rearranged p53 gene with loss of normal allele in a low-grade nonrecurrent glioma. AB - We are studying the p53 gene profile in primary glial tumors by seeking alterations in the hybridization pattern of the tumor DNA probed with a p53 gene probe. This report documents a rearranged p53 gene with loss of the normal allele in a low-grade mixed glioma which has not recurred during 4-year follow-up. The tumor had a low 5-bromodeoxyuridine (BrdU)-labeling index and low AgNOR count. The p53 protein was not detected on immunochemical staining. To our knowledge, this is the first report of an altered p53 gene in a low-grade nonrecurrent glial tumor and highlights the presence of further checks and balances on the control of cell proliferation and other malignancy-associated phenotypes, even in an already-established tumor. PMID- 7987809 TI - Chromosome derived from translocation(1;17) retains alphoid sequences of both chromosomes involved. AB - Examining a bone marrow (BM) karyotype of a patient with a refractory anemia with excess of blasts (RAEB), we detected a clone with an unbalanced translocation(1;17), resulting in monosomy of 17p and trisomy of 1q. Using fluorescence in situ hybridization (FISH) technique with alpha-satellite DNA probes specific for chromosomes 1 and 17, we observed that the chromosome derived from the translocation shows hybridization signals for both the centromeres of chromosomes 1 and 17. This finding suggests that the breakpoints of the two autosomes involved in the rearrangement occurred in the primary constriction. The case confirms the ability of ISH analysis to detect structural rearrangements in cancer cytogenetics. PMID- 7987810 TI - Expression of fragile sites in patients with retinoblastoma, their parents, and unaffected siblings: a study of ten families. AB - The expression of fragile sites (FS) in the blood lymphocytes of 54 individuals, including 11 retinoblastoma (Rb) patients, their clinically healthy family members, and corresponding age- and sex-matched controls is presented. 5 fluorodeoxyuridine (5-FdU) and caffeine were used for FS induction. Enhanced expression of fra(13)(q13.2) was observed in the patient group as compared with controls. One of the patients had a constitutional del(13)(q14.2q21.2). In this individual, only the nondeleted homologue expressed the fra(13)(q13.2). Expression of fra(13)(q13.2) in two of the patients' unaffected younger siblings of different families showed statistically significant values. The possible relation between enhanced expression of FS and the inheritance of a genetic predisposition to Rb requires further examination. PMID- 7987811 TI - Absence of trisomy 7 in nonneoplastic human ascitic and pleural fluid cells. An interphase cytogenetic study. AB - Trisomy 7 is a frequent aneuploid change in lymphomas, adenocarcinomas, and malignant mesenchymal and neurogenic tumors. Moreover, it has been observed in cultured and uncultured non-neoplastic cells from brain, kidney, liver, lung, and atherosclerotic plaques, among other tissues, opening debate on the role of this change in normal and neoplastic tissue. We used nonradioactive in situ hybridization (ISH) with a biotinylated chromosome 7-specific alpha-satellite DNA probe to seek an extra copy of chromosome 7 in ascitic and pleural fluid interphase cells from 26 donors. The donors comprised 24 patients with nonmalignant clinical history, one patient with non-Hodgkin's malignant lymphoma (positive control), and one patient with chronic myeloid leukemia (CML, negative control). The highest frequency of fluid cells with three hybridization signals in patients without neoplasia was 0.5%, in contrast to the frequency of 40.5% noted in the fluid cells of the patient with non-Hodgkin's malignant lymphoma. The results demonstrate that the frequency of trisomic cells in pleural as well as in ascitic fluid is very low, making possible use of the cells in ascitic or pleural fluids in identification of malignancy. PMID- 7987812 TI - Trisomy 11 and other nonrandom trisomies in congenital fibrosarcoma. AB - Chromosome studies in a 7-week-old female infant with an intraabdominal malignant fibrosarcoma showed a hyperdiploid karyotype of 50,XX, +der(6)del(6)(p23)add(6)(q11), +8, +10, +11,add(12)(p13). Trisomy 11 appears to be a nonrandom primary cytogenetic abnormality in the congenital or infantile form of this mesenchymal tumor and is also a nonrandom gain in congenital mesoblastic nephroma. A possible developmental link between these two mesenchymal tumors, mediated by a gene or genes on chromosome 11 is postulated. PMID- 7987813 TI - Detection of methylcytosine-rich heterochromatin on banded chromosomes. Application to cells with various status of DNA methylation. AB - A procedure including incorporation of 5-bromodeoxyuridine (BrdU) in DNA and a thermal denaturation step was developed to obtain both R-banding and efficient binding of anti-5-methylcytosine antibodies on metaphase chromosomes. BrdU incorporation improved the efficiency of antibody binding disclosed by immunofluorescence staining. This method allowed semiquantitative analysis of the antibody binding sites on straightforward characterized metaphase chromosomes and was applied to normal human lymphocytes and lymphoblastoid cell lines for which DNA methylation status had been previously analyzed. A correlation was established between level of DNA methylation and the semiquantitative estimate of antibody fixation. This procedure can be used to study DNA methylation on metaphase chromosomes in transformed and cancerous cell lines. PMID- 7987814 TI - Deletion (5q) in a desmoid tumor of a patient with Gardner's syndrome. AB - Desmoid tumors are associated with as many as 20% of cases of familial adenomatous polyposis (FAP) and Gardner's syndrome. In the present study, four specimens from different regions of a massive intraabdominal desmoid tumor from a 23-year-old white male with Gardner's syndrome were analyzed cytogenetically. Two different clonal abnormalities were observed. Two of the four specimens analyzed showed a del(5)(q14q31), which involves the region q21-->22 where the familial adenomatous polyposis gene is localized. In the two other specimens, a balanced translocation involving chromosomes 3 and 4 and an inv(4) was detected. Our findings confirm previous reports about the importance of chromosome defects on 5q in development of desmoid tumors, particularly in patients with Gardner's syndrome. PMID- 7987815 TI - Chromosomal abnormalities in the lymphocytes of a male patient with breast cancer. AB - Blood lymphocyte cultures of a male with carcinoma of the breast revealed both numerical (hypodiploidy and hyperdiploidy) and structural abnormalities. Only few cases of male breast cancer have been cytogenetically characterized. Earlier studies revealed normal karyotypes in peripheral blood cultures of male breast cancer patients and abnormalities only in the tumor tissue. The present report describes 16.6% abnormal metaphases detected in the peripheral blood lymphocytes. Numerical abnormalities were loss of chromosome 9 and 19 and gain of chromosome 7. Structural abnormalities were a cell with marker, del(11)(q22-23) and dic(7;19)(q36;p13). These abnormalities are compared with male and female tumor karyotypes reported in the literature. PMID- 7987816 TI - Characterization and localization of the TCL-1 oncogene product. AB - The TCL-1 gene maps at chromosome 14q32.1 and is activated in T cell leukemias and lymphomas by either chromosome translocations or inversions that juxtapose the TCL-1 gene to the alpha/delta or the beta locus of the T cell receptor. The open reading frame of the TCL-1 gene, coding for a protein of 114 amino acids, was expressed in bacteria and antisera were raised against it. The antibodies recognized the predicted TCL-1 M(r) 14,000 protein product in cells expressing TCL-1 mRNA. Cell fractionation experiments indicated that the TCL-1 protein is present in the microsomal fraction. These results were confirmed by confocal microscopy. The TCL-1 protein has considerable sequence similarities to the product of the MTCP-1 gene on chromosome Xq28, which is involved in T cell lympho proliferative diseases. Thus, TCL-1 may represent a member of a novel family of genes involved in lymphoid proliferation and/or survival and in T cell malignancies. PMID- 7987817 TI - Sialyl-Tn antigen expression occurs early during human mammary carcinogenesis and is associated with high nuclear grade and aneuploidy. AB - Sialyl-Tn (STn) antigen represents an aberrant glycosylation product of cell surface mucin in adenocarcinomas. We studied its expression in 40 breast carcinomas (35 of which included in situ carcinomas) by performing immunostaining with B72.3 monoclonal antibody. STn expression was observed in 50% of cases and was equally frequent in in situ and in invasive carcinomas. Positive STn staining significantly correlated with high nuclear grade (P = 0.001), aneuploidy (P < 0.001) and high S-phase fraction (P = 0.02). No correlation was observed between STn staining and age, menopausal status, presence of invasive component, or hormone receptor positivity. STn staining may provide an objective marker of dedifferentiation of breast tumors and should be investigated further for its prognostic value in breast cancers and as a biomarker of malignant transformation of breast epithelium. PMID- 7987818 TI - Preloading with L-tyrosine increases the uptake of boronophenylalanine in mouse melanoma cells. AB - To improve the effectiveness of boron neutron capture therapy, the possibility of stimulating boron uptake was investigated in an experimental model. B16F1 mouse melanoma cells were exposed to boronophenylalanine (BPA). The intracellular boron concentration followed Michaelis-Menten kinetics in the early incubation phase. In the late phase, cellular boron concentration was linearly related to the BPA concentration in the culture medium. Incubation with L-tyrosine before exposure to BPA (preloading) increased the intracellular boron concentration by a factor of three. It is concluded that in B16F1 cells BPA is transported by L and presumably ASC (alanine, serine, and cysteine) transport systems, and that boron uptake can be effectively stimulated by L-tyrosine preloading. PMID- 7987819 TI - Instability of microsatellites in rat colon tumors induced by heterocyclic amines. AB - Microsatellite instability in rat colon tumors induced by heterocyclic amines was examined by studies on the lengths of 85 microsatellite sequences, covering most of the rat chromosomes in tumors and normal tissues. Seven of eight colon tumors induced by 2-amino-1-methyl-6- phenylimidazo-[4,5-b]pyridine showed alterations at least at one locus of microsatellite sequences, whereas no mutations were observed in colon tumors induced by 2-amino-3-methylimidazo[4,5-f]quinoline. Three 2-amino-1-methyl-6-phenylimidazo-[4,5-b]pyridine-induced colon tumors had mutations in more than one microsatellite, their mutation rates being 2 of 85, 2 of 85, and 3 of 85 allele/mircrosatellite sequence, respectively. These data suggest that rat colon adenocarcinomas induced by 2-amino-1-methyl-6- phenylimidazo-[4,5-b]pyridine but not 2-amino-3-methylimidazo[4,5-f] quinoline show a trait of microsatellite instability. This is the first systematic study of microsatellite instability in experimental animal models of carcinogenesis. PMID- 7987820 TI - Boron neutron capture therapy: boron biodistribution and pharmacokinetics of Na2B12H11SH in patients with glioblastoma. AB - Data on biodistribution and pharmacokinetics of Na2B12H11SH are few and lack in standardization. This study comprises a uniform series of 10 patients with glioblastoma administered Na2B12H11SH i.v. 24 h before surgery at a dose level used in earlier therapeutical trials (75 mg/kg body weight). Boron concentrations in tumor, normal brain, peritumoral edematous brain, blood, and urine were determined by inductively coupled plasma-atomic emission spectroscopy 24 h after Na2B12H11SH administration; boron uptake in tumor (mean, 12.2 micrograms/g) was sufficiently selective compared to concentrations in normal and edematous brain (1.2 and 2.3 micrograms/g, respectively). Mean concentration ratio of tumor:blood was slightly above unity. Boron concentration in blood decreased according to an open two-compartment model, mean excretion in urine over 24 h was 81.9%. The only side effect was an inconstant facial flush. Among efforts aiming at an optimized treatment protocol a dose escalation study seems to be justified. PMID- 7987821 TI - CDKN2 (p16/MTS1) gene deletion or CDK4 amplification occurs in the majority of glioblastomas. AB - Forty-six glioblastomas, 16 anaplastic astrocytomas, and 8 astrocytomas were studied for the loss of the CDKN2 (p16/MTS1) gene on 9p. The CDKN2 locus was homozygously deleted in 19 of 46 glioblastomas (41%) and 1 allele was lost in an additional 13 cases (28%). The deleted regions were limited centromerically in some cases by the MTS2 locus and telomerically by the 1063.7 locus. CDKN2 was homozygously deleted in 3 of 16 anaplastic astrocytomas (19%) and 2 further cases showed loss of 1 allele. Amplification of the CDK4 gene was present in 7 of 14 (50%) glioblastomas and 3 of 11 (27%) anaplastic astrocytomas with no losses at the CDKN2 locus as well as in 2 of 32 (6%) glioblastomas with CDKN2 losses. Thus one or more of these two genes were shown to be aberrant in 85% of glioblastomas and 50% of anaplastic astrocytomas. None of the 8 astrocytomas showed abnormalities of these genes. PMID- 7987822 TI - Detection of sequence-specific antitumor alkylating agent DNA damage from cells treated in culture and from a patient. AB - Detection of sequence-specific DNA damage induced by antitumor alkylating agents might provide a mechanism for detecting and discriminating damage specific to one or more of these drugs. Using repetitive primer-extension and human alphoid DNA as a substrate, lesions specific for an activated form of cyclophosphamide, 4 hydroperoxycyclophosphamide, were detected at 32 of 33 guanines within a 200-base pair region in DNA from cells treated in culture. There was a marked variation in lesion site intensity among affected guanines. For instance, guanines flanked by cytosine were weak sites of 4-hydroperoxycyclophosphamide-induced damage. Damage at bases other than guanine induced by cisplatin, UV irradiation, and adozelesin were compared to drug-DNA lesions induced by 4-hydroperoxycyclophosphamide. Using this method it was possible to detect, and at some sites distinguish, between cyclophosphamide- and cisplatin-induced DNA damage within WBC DNA from a patient treated with both agents. There was a different damage pattern for DNA derived from cells treated in culture compared to DNA derived from the patient sample. PMID- 7987823 TI - Kinetics of the in vivo interconversion of the carboxylate and lactone forms of irinotecan (CPT-11) and of its metabolite SN-38 in patients. AB - The kinetics of the in vivo interconversion of the carboxylate and lactone forms of the prodrug irinotecan, 7-ethyl-10-[4-(1-piperidino)-1- piperidino]carbonyloxycamptothecin (CPT-11), and its active metabolite SN-38 were studied in five patients using a HPLC method that allows the simultaneous determination of all four compounds and detects any hydrolysis of lactones due to inadequate sample handling and storage. The apparent conversion of CPT-11 lactone to the carboxylate in vivo was rapid with a mean half-life of 9.5 min; the carboxylate became the predominant form of plasma CPT-11 soon after the end of the infusion. The ratio of the area under the plasma concentration-time curves of the lactone to total CPT-11 was 36.8 +/- 3.5% (SD). In contrast, SN-38 was present predominantly as the lactone at all times and with little interpatient variability (lactone/total area under the plasma concentration-time curve ratio, 64.0 +/- 3.4%). This may explain in part the promising activity of CPT-11 because CPT derivatives are active against their target, topoisomerase I, only in their lactone form. PMID- 7987824 TI - Somatostatin analogue octreotide enhances the antineoplastic effects of tamoxifen and ovariectomy on 7,12-dimethylbenz(alpha)anthracene-induced rat mammary carcinomas. AB - The efficacy of tamoxifen and ovariectomy in the management of breast cancer is limited by the resistance of many neoplasms to these endocrine therapies and by the fact that initially responding tumors often escape from control during long term treatment. We evaluated the effect of coadministration of the somatostatin analogue octreotide, which has single agent activity in several in vivo and in vitro breast cancer models, on the antineoplastic actions of tamoxifen and ovariectomy on 7,12-dimethylbenz(alpha)anthracene-induced mammary tumors. Rats received tamoxifen (0.5 mg/kg twice weekly s.c.), octreotide (10 micrograms/kg/h for 6 weeks by osmotic minipump), or the combination 7 weeks following 7,12 dimethylbenz(alpha)anthracene administration. The number of tumors per animal and the sum of the volumes of palpable tumors per animal were significantly less in the combination treatment than in the others. In ovariectomized rats the marked regression of established tumors in the initial 4 weeks after ovariectomy was frequently followed by tumor regrowth. However, continuous infusion of octreotide (50 micrograms/kg/h for 6 weeks postovariectomy) significantly (P < 0.01) suppressed this regrowth. Our data suggest that octreotide enhances the antitumor effects of tamoxifen or ovariectomy in the 7,12-dimethylbenz(alpha)anthracene mammary cancer model. PMID- 7987825 TI - Mutation rate of the CDKN2 gene in malignant gliomas. AB - The CDKN2 gene encodes p16, a protein controlling the cell cycle. CDKN2 is deleted in a relevant number of tumor cell lines, but results of the studies in primary tumors are contradictory. We have investigated by using quantitative polymerase chain reaction and single-strand conformation polymorphism analysis the structure of exon 2 of CDKN2 in 32 malignant gliomas. In 11 tumors the amount of amplified material was 21% of that of controls and in 8 tumors it was 42.3%, suggesting the presence of homozygous and hemizygous deletions of the CDKN2 gene, respectively. However, no abnormality could be detected by single-strand conformation polymorphism analysis. The data confirm in primary gliomas that homozygous deletions are a mechanism of CDKN2 inactivation and suggest that another gene in the vicinity could be targeted by mutations. PMID- 7987826 TI - Identification of a microsatellite instability phenotype in meningiomas. AB - To better understand the molecular mechanisms responsible for meningioma tumorigenesis we previously utilized subtractive hybridization protocols to identify genes the expression or structure of which is altered in these common brain tumors. Here we show that a CA dinucleotide repeat element present in one complementary DNA isolated by this approach has undergone a contraction in size in a meningioma cell line. Extension of this initial observation has revealed widespread genetic alterations affecting simple repeat sequences in this and other meningiomas. These data indicate that genetic instability may play a previously unrecognized role in the etiology of meningiomas. PMID- 7987827 TI - Mcl-1, a member of the Bcl-2 family, delays apoptosis induced by c-Myc overexpression in Chinese hamster ovary cells. AB - Mcl-1, a protein increased early in the differentiation of human myeloblastic ML 1 cells, has sequence similarity to Bcl-2. In the present study, we determined whether Mcl-1 has functional similarity to Bcl-2 by testing its ability to inhibit apoptosis induced by c-Myc overexpression. This was carried out using Chinese hamster ovary 5AHSmyc cells which contain the human c-myc proto-oncogene under the control of a heat shock promoter. Heat treatment induces c-Myc overexpression and thus apoptosis as determined by internucleosomal DNA fragmentation. We transfected 5AHSmyc cells with mcl-1 and found that clones expressing the introduced Mcl-1 protein exhibited reduced DNA fragmentation. Mcl 1 was also capable of delaying the onset of cell death as judged by loss of membrane integrity, although it could not provide complete protection from c-Myc overexpression. Thus, Mcl-1 has functional homology to Bcl-2 in that Mcl-1 can enhance cell viability under conditions that otherwise cause apoptosis. PMID- 7987828 TI - Deletion of p16 and p15 genes in brain tumors. AB - We have used molecular genetic methods to examine the status of cell cycle inhibitory genes in human brain tumors. We found that p16 and a neighboring gene, p15, were often homozygously deleted in glioblastoma multiformes but not in medulloblastomas or ependymomas. The deletions occurred in both primary tumors and their derived xenografts, but no intragenic mutations in either of the two genes were found. The p15 gene was expressed in a more widespread pattern in normal tissues than p16, but the products of both genes had similar capacities to bind to cyclin D-dependent kinases 4 and 6. These data suggest that the target of deletion in glioblastoma multiforme includes both p15 and p16 genes. The reason that homozygous deletions, rather than intragenic mutations, are so common in these tumors may be that deletion is a more efficient mechanism for simultaneous inactivation of both genes. PMID- 7987830 TI - Loss of heterozygosity in human primary prostate carcinomas: a possible tumor suppressor gene at 7q31.1. AB - We studied loss of heterozygosity (LOH) on human chromosome 7q to determine the location of a putative tumor suppressor gene (TSG) in human primary prostate carcinomas. Samples were obtained from 16 primary prostate carcinomas surgically removed from patients at The University of Texas M. D. Anderson Cancer Center. Paired normal and tumor DNAs were used as template for PCR amplification of a set of 14 CA microsatellite repeats on 7q21-qter. Twelve of 16 cases studied had LOH at one or more loci on 7q. Eighty-three percent LOH (five of six informative cases) was detected with D7S522 at 7q31.1-7q31.2. Percentage of LOH was normally distributed around D7S522. The high incidence of LOH in primary prostate carcinomas suggests that there is a TSG relevant to the development of prostate cancers at 7q31.1-31.2, confirming our previous functional evidence for a TSG at this location. Further research needs to be conducted to establish the identity and function of this putative TSG. PMID- 7987829 TI - A ribozyme which discriminates in vitro between PML/RAR alpha, the t(15;17) associated fusion RNA of acute promyelocytic leukemia, and PML and RAR alpha, the transcripts from the nonrearranged alleles. AB - Acute promyelocytic leukemia (FAB M3) is distinguished by the presence of the t(15;17) and clinical response to all-trans retinoic acid (RA) treatment. Acute promyelocytic leukemia is associated with a chromosomal translocation which results in the fusion of genes encoding a putative transcription factor (PML) and the retinoic acid receptor alpha (RAR alpha). It is suggested that the PML/RAR alpha fusion protein functions as an inhibitor of myeloid differentiation. The potential use of ribozymes as therapeutic agents has been investigated in the present study. Hammerhead ribozymes, which by hybridizing to both PML and RAR alpha sequences discriminate between the fusion transcript and the normal transcripts from the nonrearranged alleles, were designed and synthesized. Two hammerhead cleavage sites were targeted: site 1, an AUU located 4 nucleotides 3' to the fusion junction; and site 2, a UUC located 26 nucleotides 3' to the junction. Both sites are located in the RAR alpha portion of the fusion transcript. Using a full-length PML/RAR alpha RNA or an RNA corresponding to 788 nucleotides of the PML/RAR alpha mRNA and a full-length RAR alpha RNA or an RNA corresponding to 960 nucleotides of the RAR alpha mRNA as model substrates, the catalytic behavior of several ribozymes was studied. A modified hammerhead directed against site 2 displayed the highest degree of selectivity for PML/RAR alpha. It is hypothesized that ribozyme-mediated inactivation of PML/RAR alpha provides a new approach to study the role of PML/RAR alpha in the deregulated growth and RA response of acute promyelocytic leukemia. PMID- 7987831 TI - The search for BRCA1. AB - BRCA1, a gene predisposing to breast and ovarian cancer, was mapped to chromosome 17q21 by linkage analysis. Loss of heterozygosity in breast and ovarian tumors from BRCA1-linked patients always involved loss of wild-type alleles from chromosome 17q21, suggesting that BRCA1 acts as a tumor suppressor gene. Meiotic recombination in linked families constrained the BRCA1 region to an estimated physical size of 650 kilobases. Twenty-two candidate genes were isolated by screening complementary DNA libraries with yeast artificial chromosomes and cosmids from the critical region. Of these, 8 were known human genes, 7 were homologues of genes identified in other species, and 7 encoded novel transcripts. Each gene were sequenced and analyzed for variation, revealing 44 variants, including two missense mutations in two genes which segregated with breast cancer and were not found in controls. However, no frame-shift, nonsense, or regulatory mutations were found. PMID- 7987832 TI - Insulin protects against hepatic bioenergetic deterioration induced by cancer cachexia: an in vivo 31P magnetic resonance spectroscopy study. AB - The bioenergetic effects of cancer cachexia on the livers of male Fischer rats inoculated with a methylcholanthrene-induced sarcoma were assessed using serial in vivo 31P magnetic resonance spectroscopy. Rats were randomized into three groups: tumor-bearing controls (n = 7); an insulin-treated group receiving 2 units/100 g body weight/day starting 21 days after implantation (n = 8); and a chronic insulin-treated group receiving insulin every day after implantation (n = 3). During the 32-day study, serial measurements of food intake, body weight, and tumor volume were taken, and 31P magnetic resonance spectroscopy analyses of the livers were conducted every 7 days after tumor implantation. Neither the short term nor the chronic insulin treatment regimens stimulated the progress of tumor growth. However, both treatments prevented body weight loss, and the short-term insulin treatment prevented tumor-induced decrease in food intake relative to the control group. Liver bioenergetic deterioration was evaluated from the increase in the ratio of Pi to ATP obtained from the hepatic 31P magnetic resonance spectra. At day 28 postimplantation, control rats exhibited appreciable hepatic bioenergetic deterioration, i.e., a Pi/ATP ratio of 1.41 +/- 0.35 (SE), significantly higher (P < 0.05) than the Pi/ATP ratio for short-term or chronic insulin treatment groups (Pi/ATP 0.92 +/- 0.22 and 0.84 +/- 0.22, respectively) or rats before tumor implantation (Pi/ATP 0.76 +/- 0.14). This insulin-induced bioenergetic protection occurred at any given tumor burden up to at least 10%. Thus, both short-term insulin given just prior to the frank manifestations of cancer cachexia and chronic insulin treatment given throughout tumor growth ameliorated host hepatic bioenergetic deterioration without significantly stimulating tumor growth. Insulin may act by altering the host metabolism (stimulation of liver glucose uptake and utilization, decreased energy-requiring gluconeogenesis, and general protein-sparing action) at the expense of the tumor. PMID- 7987833 TI - Quantitative analysis of protein synthesis inhibition by transferrin-toxin conjugates. AB - A mathematical model was developed which relates the time and concentration dependence of protein synthesis inhibition of an immunotoxin to the properties of the targeting agent and the conjugated toxin. The role of the targeting agent and that of the toxin in determining the cytotoxicity were separated in this model by describing protein synthesis inhibition as a function of a cellular trafficking variable, which is calculated from the trafficking parameters of the targeting agent, and a protein synthesis inhibition constant, which is a property of the translocation and enzymatic rate constants of the toxin. Transferrin cellular trafficking parameters were determined experimentally for HeLa and SK-MEL-2 cells. Protein synthesis inhibition of transferrin-gelonin and transferrin-CRM107 conjugates in both cell lines was measured as a function of time and concentration. Analysis of the data showed that the model was a good representation of the experimental results, and correctly explained cell line differences in sensitivity to transferrin-toxin conjugates. The translocation rate constant for transferrin-CRM107 was approximately 3000 times greater than that for transferrin-gelonin. The model may be useful in understanding the factors that influence immunotoxin efficacy and in designing more lethal immunotoxins. PMID- 7987834 TI - An overexpressed N-ras proto-oncogene cooperates with N-methylnitrosourea in mouse mammary carcinogenesis. AB - The induction of tumors with chemicals and the production of transgenic animals are two experimental approaches to study oncogene involvement in carcinogenesis. The combination of both strategies offers an excellent model system to study tumor development. This study analyzes the potential cooperation of N methylnitrosourea (MNU) treatment and N-ras proto-oncogene overexpression in tumorigenesis in transgenic mice. The overexpression of the N-ras proto-oncogene in these animals is associated with development of mammary tumors and lymphomas. After MNU treatment we analyzed tumor incidence and latency, levels of transgene expression, and pattern of ras mutations in codons 12, 13, and 61 of H-, K-, and N-ras genes in both tumor types. Transgenic mice treated with MNU had significantly (P < 0.001) shorter latency of appearance of mammary tumors [8.6 +/ 3.0 (SD) months] than phosphate-buffered saline-treated transgenics (12.8 +/- 2.3 months). All mammary tumors overexpressed the N-ras transgene and lacked ras mutations. Moreover, MNU-treated transgenics had an incidence and latency of lymphomas similar to that of MNU-treated nontransgenic mice. No significant differences in incidence of point mutations (K-ras codon 12 or 13 and N-ras codon 61) in lymphomas were seen between these two groups. All lymphomas overexpressed the N-ras transgene, except for those carrying a K-ras point mutation. Overexpression of the N-ras proto-oncogene cooperates with non-ras genes mutated by MNU in mouse mammary carcinogenesis. Conversely, N-ras proto-oncogene overexpression does not show cooperation with MNU in lymphomagenesis in our system. This study suggests that proto-oncogene overexpression may be a mechanism of activation of the ras pathway, alternative to point mutation. Similarly to actions for ras genes activated by point mutation, overexpression of the N-ras protooncogene predisposes to tumorigenesis and cooperates with a carcinogen in tumorigenesis. The possibility that ras overexpression plays a role in human breast tumorigenesis requires active investigation. PMID- 7987835 TI - Altered oxidative stress responses in nickel-resistant mammalian cells. AB - BALB 3T3 cells exposed to NiCl2 acquired resistance to concentrations as high as 200 microM and retain resistance for many generations in the absence of nickel. This resistance was not due to alterations in uptake or to metallothionein overexpression. The nickel-resistant B200 cell line was found to also exhibit cross-resistance to hydrogen peroxide and menadione. These nickel-resistant cells had 1.8 times higher basal levels of glutathione compared to wild-type cells. Studies with the glutathione synthesis inhibitor buthionine sulfoximine showed that while glutathione turnover was more rapid in the nickel-resistant cells, its depletion following NiCl2 treatment of the parental BALB 3T3 cell line was greater than in the nickel-resistant B200 cells. The reduced level of binding of NFkB and AP-1 transcription factors to their DNA consensus sequences in B200 cells compared to wild-type cells, and their more reactive response following treatment of resistant cells with H2O2 or buthionine sulfoximine, strengthens the hypothesis that nickel resistance is closely allied to oxidative stress responses. PMID- 7987836 TI - Alterations in murine keratinocyte differentiation induced by activated rasHa genes are mediated by protein kinase C-alpha. AB - Primary mouse keratinocytes expressing the v-rasHa oncogene (v-rasHa keratinocytes) produce squamous papillomas when grafted onto nude mice and respond abnormally to signals for terminal differentiation both in vivo and in vitro. Since protein kinase C (PKC) activators and v-rasHa induce similar phenotypic changes in cultured keratinocytes, and cellular diacylglycerol levels are constitutively elevated in ras-transformed keratinocytes, we tested whether PKC is a downstream target for oncogenic ras in this cell type. Ca(2+)-dependent PKC activity was increased in lysates from cultured v-rasHa keratinocytes when compared to control cells; in contrast, Ca(2+)-independent activity decreased. Similar to PKC activators, v-rasHa blocked Ca(2+)-mediated expression of the early epidermal differentiation markers keratins K1 and K10 while inducing aberrant expression of K8. Pretreatment of v-rasHa keratinocytes with bryostatin to block PKC function restored Ca(2+)-mediated expression of K1 and K10 and blocked abnormal expression of K8, suggesting that these responses are mediated by the PKC pathway. Furthermore, expression of K1 is restored at bryostatin doses which specifically down-modulate PKC-alpha, the only Ca(2+)-dependent PKC isozyme detected in cultured keratinocytes. In contrast to the inhibition of K1 and K10, Ca(2+)-induced expression of the late epidermal differentiation markers loricrin, filaggrin, and keratinocyte transglutaminase was accelerated by v-rasHa, as previously reported in normal keratinocytes treated with PKC activators. Pretreatment of v-rasHa keratinocytes with bryostatin blocked expression of late markers in these cells, and this response was correlated with down-regulation of PKC-alpha. The results of this study suggest that oncogenic ras alters keratinocyte differentiation by altering the function of the PKC signaling pathway, and that PKC-alpha is the specific isozyme involved in down-modulating expression of keratins K1 and K10 and up-regulating expression of loricrin, filaggrin, and keratinocyte transglutaminase. PMID- 7987837 TI - Clinical pharmacokinetics of cyclophosphamide and metabolites with and without SR 2508. AB - The pharmacokinetics of cyclophosphamide (CP) and several important metabolites was studied in detail in six patients receiving CP alone and with a radio- and chemosensitizing agent, SR-2508. CP at 1000 mg/m2 was either infused in 20 min alone or given 2 h before an infusion of SR-2508 at 5 g/m2 over 20 min, both separated by 3 weeks, to the same patients in a randomized fashion. Plasma and 24 h urinary levels of CP and four metabolites: [4-hydroxycyclophosphamide (4-OH CP), phosphoramide mustard (PM), chloroethyl oxazolidin-2-one, and alcophosphamide] were monitored by a gas chromatographic-mass spectrometric stable isotope dilution assay. CP plasma levels were found to decline monoexponentially with the appearance of transient saturation kinetics in some and a mean t1/2 of 5.2 h for patients treated with CP alone. Plasma 4-OH CP levels showed a mean peak concentration of 2.4 microM and declined approximately in parallel to those of CP. The major circulating metabolite was found to be PM with a mean peak concentration of 40 microM and a terminal t1/2 of 15 h. The mean area under the plasma concentration curve (AUC) ratios between metabolites and CP were: 4-OH CP, 0.0158; PM, 0.4518; and chloroethyl oxazolidin-2-one, 0.179 with alcophosphamide at low levels. No appreciable amount of nornitrogen mustard was detected. Mean urinary excretion was: CP, 10.8; 4-OH, CP, 0.5; PM, 39.0; alcophosphamide, 0.4; and chloroethyl oxazolidin-2-one, 3.0, all expressed as a percentage of CP dose. No statistically significant difference was detected in all standard pharmacokinetic parameters determined for both CP and metabolites between patients with CP alone and with SR 2508. Plasma 4-(p-nitrobenzyl)pyridine activity was found to correlate the closest with PM profiles, with respect to both standard pharmacokinetic parameters and AUC values. When plasma PM AUC values were plotted against AUC values of circulating 4-(p-nitrobenzyl)pyridine activity, a correlation coefficient of 0.859 (P < 0.001) was obtained. Together with the significant cytotoxicity of PM these data support a significant contribution of circulating PM in the antitumor effect of PM. PMID- 7987838 TI - Analysis of the energy balance in lung cancer patients. AB - Previous studies have shown that an elevated resting energy expenditure (REE) frequently occurs in lung cancer patients. The aim of the present study was to assess the balance between REE and dietary intake and to analyze the contributing factors of elevated REE in newly detected lung cancer patients. One hundred newly detected lung cancer patients were evaluated. Measured values of REE were adjusted for the values predicted by the Harris-Benedict formula and for fat-free mass assessed by the bioelectrical impedance method. Dietary intake was measured using a dietary history. A substantial number of patients (30%) had a weight loss of 10% or more from their preillness stable weight. An elevated REE was found in 74% of the patients. Stratification by tumor localization revealed that patients with a central tumor had a significantly higher REE [121 +/- 13% (SD) versus 110 +/- 10% of predicted, P < 0.001] and significantly higher level of C-reactive protein (35 +/- 35 mg/liter versus 16 +/- 26 mg/liter, P = 0.006) compared with patients with a peripheral tumor. Dietary intake was significantly lower in the weight-losing group (1872 +/- 542 kcal/day versus 2169 +/- 782 kcal/day, P < 0.05) compared with the weight-stable group. We conclude that both elevated REE and decreased dietary intake contribute to weight loss in lung cancer patients. Tumor localization and inflammation were found to be contributing factors to the elevated REE. PMID- 7987839 TI - Ectopic vasopressin expression in MMTV-Wnt-1 transgenic mice modifies mammary tumor differentiation and pathology. AB - A transgenic mouse model has been developed to test the involvement of ectopic neuropeptide production as a secondary factor in cancer. Mice bearing a mouse mammary tumor virus-vasopressin (MMTV-VP) fusion transgene synthesized authentic vasopressin in mammary ducts and alveoli, but this had no effect on mammary gland development and growth. Mice bearing the MMTV-VP transgene were then mated with mice bearing the MMTV-Wnt-1 transgene to produce bitransgenic animals. Two types of mammary tumor develop in MMTV-Wnt-1 mice; type A mammary adenocarcinomas are uniform with fine acinar structure composed of small epithelial cells arranged to form round cavities and elongated tubules, while adenocarcinoma type B tumors have acinar areas, cystic spaces filled with blood or fluid, intracystic papillary projections, and cords as well as sheets of cells. Compared to the MMTV Wnt-1 mice, the bitransgenic animals developed proportionally less type B tumors. Further, type B mammary adenocarcinomas from bitransgenic mice exhibited increased proliferation and growth, as judged by mitotic index and argyrophilic nucleolar organizer region counts, compared to type B tumors from MMTV-Wnt-1 mice. These data provide evidence that ectopic neuropeptide production can modulate the development of tumors in vivo. PMID- 7987841 TI - Increasing 1-beta-D-arabinofuranosylcytosine efficacy by scheduled dosing intervals based on direct measurements of bone marrow cell kinetics. AB - The therapeutic efficacy of cell cycle phase-specific drugs can be improved by repeated administrations, the dosing interval being related to the cell cycle time of the susceptible normal host tissue. Kinetic measurements of bone marrow cell proliferation, with bromodeoxyuridine labeling and flow cytometry analysis, were used to determine the optimal dosing intervals of 1-beta-D arabinofuranosylcytosine for minimizing bone marrow cell damage in mice. The results showed that cells surviving a single dose 1-beta-D arabinofuranosylcytosine treatment remained temporarily blocked at the G1-S boundary, and upon release from the block the cells crossed through S phase in a nearly synchronized way. The optimal spacing of repeated treatments, evaluated by measurements of the drug-induced transit times through the different cell cycle phases, equaled the bone marrow cell cycle time following treatment. Repeated 1 beta-D-arabinofuranosylcytosine injections according to this protocol markedly diminished drug toxicity in C3H mice, as compared to protocols of other time intervals. A therapeutic schedule based on these measurements was highly effective in lymphoma-bearing mice: the designed protocol of dosing intervals significantly delayed tumor growth whereas other intervals were highly toxic. PMID- 7987840 TI - Unsaturated fatty acids are required for continuous proliferation of transformed androgen-dependent cells by fibroblast growth factor family proteins. AB - Increase in dietary fat intake has been reported to be associated with progression of hormone-dependent cancers. To explore its mechanism, we examined the effects of fatty acids on the growth of androgen-dependent SC-3 cells cloned from mouse mammary cancer (Shionogi carcinoma 115). Their androgen-dependent growth was potentiated by linoleic acid in the defined medium. The effect of linoleic acid on fibroblast growth factor (FGF)-dependent growth was also addressed because androgen had been demonstrated to exert its mitogenic activity on SC-3 cells through an induction of the unique FGF family protein termed as androgen-induced growth factor. Exposure of SC-3 cells to basic FGF or androgen induced growth factor exhibited only transient growth response. However, simultaneous addition of linoleic acid to the medium sustained the proliferation of FGF-stimulated, but not FGF-unstimulated, cells, although linoleic acid did not exert the significant effect on the process of S-phase entry of basic FGF stimulated cells. Palmitoleic acid and oleic acid appeared to exert the actions similar to linoleic acid, while stearic acid was without any effect. Neither cyclooxygenase inhibitor nor 5-lipoxygenase inhibitor could block the growth promoting ability of linoleic acid. Linoleic acid also enhanced their anchorage independent growth in the presence of basic FGF. These results indicate that these unsaturated fatty acids play a role in sustaining the proliferation of FGF stimulated SC-3 cells. PMID- 7987842 TI - Enhancement of the antineoplastic effect of mitomycin C by dietary fat. AB - In the present study, we investigated the effects of high dietary fat on the growth of MX-1 heterotransplanted in athymic mice and its response to mitomycin C (MC) treatment. We found that high fat intake (25% corn oil, w/w) significantly increased tumor growth, but at the same time it also increased the tumor response to MC treatment compared to the control low fat diet (5% corn oil, w/w). In the tumors from mice fed either low (5% w/w) or high (25% w/w) fat, MC treatment induced oxidative challenge, indicated by significantly increased tumor total superoxide dismutase, catalase, glutathione peroxidase, and glutathione S transferase peroxidase activities, as well as increased tumor lipid peroxidation. On the other hand, glutathione reductase activity was inhibited by MC treatment. Some of the enzymes which are known to activate MC, such as cytochrome b5 reductase and DT-diaphorase, were also induced in the tumor by high dietary fat intake. The enzyme activities in hepatic tissues were also altered by dietary fat and MC treatment but to a lesser extent. We conclude that high dietary fat intake could enhance the chemotherapeutic effect of MC by increasing MC-activating enzyme activities. The observed increase in lipid peroxidation after MC treatment in MX-1 human mammary carcinoma implanted in the nude mice could result from the observed inhibited glutathione reductase activity. It is tempting to speculate that this might be another antineoplastic mechanism for MC in addition to its known role as a bioreductive alkylating agent. Alternatively, glutathione reductase may be a target for bioreductive alkylation. PMID- 7987843 TI - Induction of hypoxia in experimental murine tumors by the nitric oxide synthase inhibitor, NG-nitro-L-arginine. AB - The nitric oxide synthase inhibitor NG-nitro-L-arginine (NOARG) was examined for its ability to alter energy metabolism in three murine tumors using 31P magnetic resonance spectroscopy. NOARG (10 mg/kg, i.v.) increased the inorganic phosphate:total phosphate ratio (Pi:total) 2-3-fold in the KHT, RIF-1, and SCCVII/Ha intradermal back tumors from 30 min to 6 h after injection, but the 31P magnetic resonance spectrum from normal tissue on the mouse back was unchanged after this treatment. NOARG (10 mg/kg, i.v.) injected 30 min before X-rays increased tumor cell survival 3-5-fold in SCCVII/Ha and 50-200-fold in RIF-1, measured using an in vivo/in vitro clonogenic assay. These effects were equivalent to those obtained from clamped tumors, indicating full radiobiological hypoxia. In KHT, only a 2-fold increase in radioresistance was observed after NOARG, which was less than the response of clamped tumors. In RIF-1 tumors, NOARG induced full radiobiological hypoxia when given from 30 min to 6 h prior to X rays, consistent with the time course for the increase in Pi:total, measured by 31P magnetic resonance spectroscopy. Pi:total after NOARG doses of 0.1-10 mg/kg, i.v., increased in a dose-dependent manner in this tumor. Increased RIF-1 tumor radioresistance was similarly dependent on NOARG dose. The combination of the bioreductive agent RB6145 (300 mg/kg, i.p.) 15 min prior to NOARG (10 mg/kg, i.v.) produced greater than 5 decades of KHT tumor cell killing at 24 h after treatment. This combination also increased Pi:total 4.5-fold over the control value at 24 h in the KHT tumor. Histological examination of tumors at this time indicated extensive necrosis. PMID- 7987844 TI - Cross-resistance between cisplatin and antimony in a human ovarian carcinoma cell line. AB - The metal compound cisplatin (DDP) is a widely used anticancer agent but naturally occurring and acquired resistance to DDP limits its effectiveness. Resistance is associated with a decreased accumulation of DDP and increased levels of glutathione and metallothioneins. Such changes also serve as protective and detoxification mechanisms for other metal salts in prokaryotes and lower eukaryotes. The aim of this study was to find metal salts for which the cross resistance profile was the same as for DDP in sublines of the parental 2008 human ovarian carcinoma cells selected with either DDP (2008/C13*5.25) or CdCl2 and ZnCl2 (2008/MT). Among the metal salts tested the resistance profile of trivalent antimony most closely resembled that of DDP. DDP-selected cells were 15-fold resistant to DDP and 4.4-fold cross-resistant to antimony potassium tartrate, whereas of the cations tested (Cd2+, Zn2+, Ni2+ and Co2+) cross-resistance was observed only for Cd2+ (2.4-fold). When 2008 cells were selected for resistance to antimony (6.6-fold) they were found to be 16-fold cross-resistant to DDP. Accumulation of the DDP analogue cis-[3H]dichloro(ethylenediamine)platinum(II) was 59% lower in the DDP-selected subline and 48% lower in the antimony-selected variant than in the parental cell line. We conclude from the mutual cross resistance to DDP and antimony potassium tartrate and from the impaired uptake of [3H]DEP in both the DDP and antimony-selected variants that DDP and antimony share a common mechanism of resistance. The significance of this observation lies in the fact that several evolutionarily conserved mechanisms for antimony detoxification are already known in lower organisms which may point the way to identification of additional DDP resistance mechanisms in mammalian cells. PMID- 7987845 TI - Combined interleukin-1 beta/interleukin-6 treatment in mice: synergistic myelostimulatory activity and myelorestorative effect after cyclophosphamide induced myelosuppression. AB - We have studied the effects of single and combined treatment with recombinant human interleukin 1 beta (IL-1 beta) and recombinant human interleukin-6 (IL-6) on spleen and bone marrow hematopoiesis in normal and cyclophosphamide-treated mice. Injection of IL-1 beta alone resulted in a significant increase in the number of granulocytes and splenic progenitors [burst-forming units-erythroid (BFU-E) and colony-forming units-granulomonocytic (CFU-GM)] as compared with control mice but did not markedly enhance the number of bone marrow BFU-E and CFU GM. IL-6 alone had little effect on the number of splenic progenitors but significantly increased the number of marrow BFU-E and CFU-GM, especially after a 6-day cytokine treatment. Combined daily administration of IL-1 beta and IL-6 for 3 days resulted in a synergistic stimulation of hematopoiesis as evaluated by the number of spleen and bone marrow CFU-GM and BFU-E colonies. Likewise, IL-1 beta/IL-6 markedly enhanced the number of circulating neutrophils, whereas each cytokine alone had little or no effect. When the numbers of spleen progenitors and peripheral granulocytes were determined 1 day after the last injection, a synergistic myelostimulatory effect of combined IL-1 beta/IL-6 treatment was observed at all doses (IL-1 beta, 0.25-0.5 microgram; IL-6, 1-20 micrograms). Furthermore, combined treatment with IL-1 beta/IL-6 accelerated and potentiated the recovery of myeloid cells after cyclophosphamide injection, whereas the single regimen treatment was not effective. Particularly, the rebound of WBC (especially neutrophilic granulocytes) after cyclophosphamide treatment was markedly enhanced by the combined treatment, whereas the single regimen was ineffective. Altogether these results may contribute to the development of combination therapies with cytokines and antiblastic agents in the treatment of cancer patients. PMID- 7987846 TI - Deletion mapping on the short arm of chromosome 3 in squamous cell carcinoma of the oral cavity. AB - Loss of heterozygosity indicative of the presence of tumor suppressor genes on chromosome 3p is commonly observed in carcinomas of various tissues. We have examined loss of heterozygosity on chromosome 3p in 27 oral squamous cell carcinomas using 15 highly informative microsatellite polymorphisms and constructed a deletion map of chromosome 3p. Overall, loss of heterozygosity at one or more loci was observed in 14 tumors (approximately 52%). A majority of these tumors (86%) show loss in more than one area. Three distinct regions were identified: 3p13-3p21.1, 3p21.3-3p23, and 3p25. These data suggest a role for at least three tumor suppressor genes on chromosome 3p in oral squamous carcinomas. The regions of deletions overlap with those described for carcinomas of other tissues and parallel those observed in lung carcinomas. This may reflect the common etiology of the two cancers. PMID- 7987847 TI - Genetic analysis of liver tumorigenesis in SV40 T antigen transgenic mice implies a role for imprinted genes. AB - Liver tumors from interspecific hybrid, transgenic mice containing the SV40 early region linked to a mouse major urinary protein enhancer/promoter were analyzed for loss of heterozygosity to identify chromosomal regions which potentially contain genetic loci involved in multistep tumorigenesis. A broad pattern of complete and partial loss of heterozygosity or allelic imbalance was observed with frequent loss of heterozygosity/partial loss of heterozygosity of loci on chromosomes 1, 5, 7, 8, and 12. In tumors from Mus domesticus x Mus spretus F1 mice a strong preference for loss of the domesticus allele of H19 on chromosome 7 was observed, whereas loss of heterozygosity/partial loss of heterozygosity on chromosome 8 involved preferential loss of spretus alleles. In tumors from reciprocal crosses with Mus castaneus, the maternal chromosome 7 H19 allele was preferentially lost irrespective of whether it was domesticus or castaneus, strongly suggesting the involvement of an imprinted gene(s) in tumor progression. PMID- 7987848 TI - Chromosome 8 alterations accompany tumorigenesis in renin-SV40 T antigen transgenic mice. AB - s.c. and abdominal tumors from interspecific hybrid, transgenic mice containing the SV40 early region linked to a renin enhancer/promoter were analyzed for loss of heterozygosity to identify chromosomal regions involved in tumorigenesis. A very high frequency of loss of heterozygosity/partial loss of heterozygosity or allelic imbalance involving the distal regions of chromosome 8 was observed in the s.c. tumors (76%) with frequent amplification (3-6 times) of the corresponding proximal regions including Junb, suggesting that chromosome 8 breakage and amplification promotes tumorigenesis in these mice. PMID- 7987849 TI - Characterization of the CHOP breakpoints and fusion transcripts in myxoid liposarcomas with the 12;16 translocation. AB - Myxoid liposarcomas are cytogenetically characterized by t(12;16)(q13;p11). The translocation results in rearrangements of the CHOP gene in 12q13 and the FUS gene in 16p11, creating a fusion gene where the RNA-binding domain of FUS is replaced by the DNA-binding and leucine zipper dimerization domain of CHOP. In the present study, we have mapped 16 genomic breakpoints in the region of the CHOP gene and isolated and sequenced a new variant (type II) of the chimeric FUS/CHOP transcript. The genomic breakpoints were dispersed along a 7.50-kilobase pair region from a SstI cleavage site upstream of the promoter of CHOP to a PstI cleavage site within intron 1. Reverse transcriptase-polymerase chain reaction analysis of tumor samples demonstrated the presence of two variant fragments, 654 base pairs (type I) and 378 base pairs (type II) in size. Of the 13 samples analyzed, 7 showed the smaller, 3 showed the larger, and 3 showed both types of transcripts. We cloned and sequenced the two fragments and found in type II a novel fusion point in the FUS mRNA 275 base pairs upstream of that present in the type I transcript. In both types of transcripts the interrupted FUS is followed by the entire exon 2 of CHOP. As a consequence the normally nontranslated exon 2 is translated and in both types there is in the junction between FUS and CHOP a shift from a FUS glycine codon to a valine codon in the chimeric mRNA. PMID- 7987850 TI - DNA binding and transactivation activity of A-myb, a c-myb-related gene. AB - A partial-length A-myb complementary DNA recently cloned by low-stringency hybridization with a c-myb probe to complementary DNA libraries derived from human cell lines showed a high degree of homology with the DNA-binding domain of c-myb and B-myb, suggesting that A-myb also encoded a DNA-binding protein. We report here the sequence of the entire coding region of A-myb complementary DNA and show that the full-length GST-A-myb fusion protein or a truncated derivative corresponding only to the putative DNA-binding domain interacts specifically with Myb-binding sites of the c-myb responsive promoters, MIM-1 and CD34. In transient transfection assays, A-myb transactivated the bound promoters. These results suggest that, analogous to the other members of the Myb family, the A-myb gene encodes a bona fide transactivator. The distinct function of A-myb might derive from its pattern of expression and/or its relative potency as a transactivator of myb target genes. PMID- 7987851 TI - Pericellular pH affects distribution and secretion of cathepsin B in malignant cells. AB - Redistribution of lysosomes to the cell surface and secretion of lysosomal proteases appear to be general phenomena in cells that participate in local proteolysis. In the present study, we have determined whether malignant progression affects the intracellular distribution and secretion of the lysosomal protease cathepsin B in three model systems, each of which consists of cell pairs that differ in their degree of malignancy. The intracellular distribution of vesicles staining for cathepsin B was evaluated by immunofluorescent microscopy and the secretion of cathepsin B was evaluated by two complementary techniques: stopped assays of activity secreted into culture media; and continuous assays of activity secreted from viable (> or = 95%) cells growing on coverslips. We observed that the intracellular distribution of cathepsin B+ vesicles was more peripheral in the cells of higher malignancy in all three model systems and that active cathepsin B was secreted constitutively from these cells. Because an acidic pericellular pH has been shown to induce translocation of lysosomes in macrophages and fibroblasts, we evaluated the intracellular distribution of cathepsin B+ vesicles and secretion of cathepsin B in cell pairs incubated at slightly acidic pH. Acidic pericellular pH induced a redistribution of cathepsin B+ vesicles toward the cell periphery. In the more malignant cells, this resulted with time in reduced intracellular staining for cathepsin B and enhanced secretion of active cathepsin B. Translocation and secretion of cathepsin B were dependent on a functional microtubular system. Both the redistribution of cathepsin B+ vesicles toward the cell surface induced by acidic pH and the constitutive and acidic pH-induced secretion of active cathepsin B could be inhibited by microtubule poisons and stabilizers. We suggest that the redistribution of active cathepsin B to the surface of malignant cells and its secretion may facilitate invasion of these cells. PMID- 7987852 TI - The role of transforming growth factor beta 1 in the fibroblastic reaction associated with rat colorectal tumor development. AB - Many tumors are surrounded by a highly fibrous stroma composed of fibroblasts and extracellular matrix. This desmoplastic response has been suggested to both inhibit and favor tumor progression. The present study deals with the effects of tumor cells on the fibroblastic reactions they cause and relates this to progression or regression of tumors. Two rat colon carcinoma cell lines, one which develops progressive tumors when injected s.c. in syngeneic animals (PROb cell line) and the other which develops regressive tumors in similar conditions (REGb cell line), were compared by the fibroblastic reaction which they cause. Comparative histological analysis of progressive and regressive tumors developed by the two cell lines showed a significant but opposite response of fibroblastic compartment. The progressive tumor nodules were observed to grow within a loose tissue, whereas the regressive tumor cells were surrounded by a fibrous capsule. Immunohistological labelings revealed the presence of alpha-smooth muscle actin positive myofibroblasts during the tumor expansion, while these specific cells disappeared during the tumor regression. Immunostainings of transforming growth factor beta 1 showed an increasing staining of the progressive tumor cells during tumor development but a slight expression by tumor cells and stroma during the tumor regression. This growth factor was demonstrated to facilitate initial steps of the tumor progression by addition of active transforming growth factor beta 1 at the time of s.c. injection of PROb cells in syngeneic rat models. In vitro experimental analysis with the use of neutralizing antibody showed that active transforming growth factor beta produced by the progressive cells inhibited fibroblast proliferation and facilitated their differentiation into myofibroblasts. Since the number of myofibroblasts increased with time in progressive tumors, their presence may constitute a potential growth advantage for tumor growth. In contrast, our results indicated involvement of platelet derived growth factor-like protein(s) in fibroblast proliferation under the control of regressive cells and the presence of an important sheath of alpha smooth muscle actin-negative fibroblasts in regressive tumors may support a role for this growth factor in vivo. Thus, the ability of tumor cells to produce or induce the production of transforming growth factor beta or platelet-derived growth factor may give rise to a specific fibroblast reaction, which in turn may determine consequent tumor evolution. PMID- 7987853 TI - Variant type of sialyl Lewis X antigen expressed on adult T cell leukemia cells is associated with skin involvement. AB - Expression of a variant type of sialyl Le(x) antigen defined by 2F3 monoclonal antibody on leukemia cells was studied in 15 adult T cell leukemia (ATL) patients. The expression of 2F3-defined sialyl Le(x) antigen on CD4+CD45+ cells, which is an ATL cell-rich population, was higher in patients with skin involvement (50.1 +/- 23.1% were positive) than in patients without skin involvement (18.1 +/- 12.5%) (P < 0.01). The other surface markers including classical sialyl Le(x) antigen defined by SNH3 or FH6 and LFA-1, VLA-4, CD4, CD25, ICAM-1, Leu8, and HLA-DR did not show a significant difference regardless of skin involvement. In the skin lesion of four patients that we could examine, infiltrating leukemia cells strongly expressed 2F3-defined sialyl Le(x) antigen. In one patient, we could also examine the expression of classical sialyl Le(x) antigen defined by SNH-3 and CSLEX-1, but this was almost negligible. Both skin and lymph node biopsy specimens were examined in two patients. Leukemia cells in the skin strongly expressed 2F3-defined sialyl Le(x) antigen, while its expression was almost negligible on the leukemia cells in the lymph node. These findings suggest that the expression of 2F3-defined sialyl Le(x) antigen on ATL cells is associated with skin involvement of ATL. PMID- 7987854 TI - Impact of urokinase-type plasminogen activator and its inhibitor type 1 on prognosis in cervical cancer of the uterus. AB - The present study was undertaken to assess the role of tumor-associated urokinase type plasminogen activator (uPA) and its inhibitor type 1 (PAI-1) as a predictor for early relapse and poor prognosis in patients with stage II cervical cancer of the uterus. We have investigated the localization of uPA and PAI-1 immunohistochemically in formalin-fixed paraffin-embedded tissue sections. uPA and PAI-1 were analyzed antigenically, enzymologically, and zymographically in 28 patients with pelvic lymph node involvement and in 34 cases without nodal spread, as well as in 10 cases with normal cervix. In cancer tissues, strong staining for uPA was found in areas with invasive growth and degradation of surrounding normal tissue, while most tumor nests showed a mild or a moderate, evenly distributed PAI-1 staining. A significantly higher lymph node-positive rate was observed in patients having tumors with strong uPA and/or PAI-1 stainings than in those with tumors with weak stainings. In spite of significantly higher PAI-1 levels in the primary neoplastic tissues, uPA was found to be increased as well, both in antigen level and in activity. Most of PAI-1 obtained from cancer extracts is the latent form. These results suggest that cancer-associated increase in uPA seems not to be affected (or inhibited) by PAI-1 in areas where tumor cells are invading normal tissue. The overall survival and progression-free survival rate was worst in patients with the strong uPA staining confined to the tumor stromas and also with the strong PAI-1 staining at tumor nests, indicating that the greater localization of uPA in stromal cells than in malignant cells is a predictor of early relapse and poor prognosis in patients with cervical cancer of the uterus. Thus, the staining intensities and the localization of uPA and PAI-1 in tissue specimens appear to be predictors of increasing risk for lymph node metastasis, suggesting that some tumor cells recruit stromal cells to produce uPA and that PAI-1 may not act as a defense mechanism for tumor cell invasion and metastasis in the leading edge of tumor growth. PMID- 7987855 TI - 9-Cis retinoic acid inhibits growth of breast cancer cells and down-regulates estrogen receptor RNA and protein. AB - All-trans retinoic acid (tRA) inhibits growth of estrogen receptor-positive (ER+) breast cancer cells in vitro, and a variety of retinoids inhibit development of breast cancer in animal models. 9-cis retinoic acid (9-cis RA) is a naturally occurring high affinity ligand for the retinoid X receptors, as well as the retinoic acid receptors (RARs). Whether 9-cis RA has a different spectrum of biological activity from tRA, which only binds RARs with high affinity, is largely unknown. We studied the effects of 9-cis RA on growth and gene expression in ER+ and ER- human breast cancer cells. 9-cis RA inhibited the growth in monolayer culture of several ER+, but not ER-, cell lines in a dose-dependent manner. Growth inhibition and morphological changes by 9-cis RA were similar to those of tRA, suggesting that the ability to bind both RAR and retinoid X receptors did not significantly augment growth inhibition or confer sensitivity to tRA-resistant lines. MCF-7 cells exposed to 9-cis RA showed a dose-dependent accumulation in G1. Northern analyses showed that RAR-alpha and RAR-beta were not significantly regulated, while RAR-gamma was up-regulated and retinoid X receptor alpha was down-regulated by 9-cis RA. Since interactions between tRA and ER dependent transcription have recently been reported, we investigated whether these retinoids regulate expression of ER itself or estrogen-responsive genes. Both 9-cis RA and tRA induce down-regulation of ER mRNA and protein in MCF-7 cells. 9-cis RA down-regulates expression of the estrogen-responsive genes PR and pS2 in MCF-7 cells as reported previously for tRA. In several ER-positive subclones, we found that the degree of ER expression and regulation, but not always estrogen-sensitivity, correlates with the growth-inhibitory effects of 9 cis RA. Further, in an ER-, retinoid-unresponsive breast cancer cell line, induced ER expression confers responsiveness to retinoid growth inhibition. These data, combined with reports of additive growth inhibition of tRA and tamoxifen in vitro, suggest that 9-cis RA might augment the ability of tamoxifen to inhibit growth of ER+ breast cancer cells in vivo. PMID- 7987856 TI - Effects of linoleic acid on the growth and metastasis of two human breast cancer cell lines in nude mice and the invasive capacity of these cell lines in vitro. AB - The purpose of the study was to compare the effects of dietary linoleic acid (LA) intake on the growth and metastasis of MDA-MB-435 and MDA-MB-231 human breast cancer cells in nude mice, together with their invasive capacity and secretion of type IV collagenase (gelatinase) in vitro. Each tumor cell line (10(6) cells) was injected into a right-sided mammary fat pad in 60 mice with equal numbers (30 mice/group) assigned to isocaloric diets containing 23% (w/w) total fat and 2% or 12% (w/w) LA. The MDA-MB-435-cell mammary fat pad tumors became palpable earlier and initially they grew more rapidly, but by 6 weeks the MDA-MB-231-cell tumors exhibited an acceleration of growth which was enhanced by the high-LA diet. At necropsy, 12 weeks after the tumor cell injections, the mean weight [10.2 +/- 1.4 g(SEM)] of mammary fat pad MDA-MB-231 cell tumors in 12% LA-fed mice was significantly higher (6.7 +/- 1.4 g) than that of the mice fed 2% LA; also, it was higher than that of MDA-MB-435 cell tumors in the 12% LA-fed mice (3.6 +/- 0.1 g) or the 2% LA-fed mice (3.3 +/- 0.1 g) (each P < 0.001). Mice fed the 12% LA diet had a higher incidence of grossly visible MDA-MB-435 cell pulmonary metastatic nodules than those fed the 2% LA diet (67% versus 33%; P < 0.02), more metastatic lesions (5.7 +/- 1.6 versus 2.3 +/- 0.8; P < 0.05), and greater total volumes (62.0 +/- 25.9 versus 24.8 +/- 9.0 mm3; P < 0.02) per mouse. Of the MDA MB-231 cell tumor-bearing mice, only 1 in the 12% LA dietary group and 2 in the 2% LA dietary group had macroscopic nodules but the incidence of microscopic metastases was 68 and 42%, respectively. The MDA-MB-231 cell line exhibited a relatively high capacity for invasion in vitro and constitutively high levels of both total type IV collagenolytic activity and M(r) 92,000 gelatinase production which were unaffected by LA. In contrast, MDA-MB-435 cells had approximately only one-sixth the invasive capacity and secreted a relatively low level of type IV collagenase and little of the M(r) 92,000 gelatinase; both invasion and enzyme production were stimulated by LA. PMID- 7987857 TI - Enhanced expression of the tie receptor tyrosine kinase mesenger RNA in the vascular endothelium of metastatic melanomas. AB - Angiogenesis of human melanomas has been the focus of intense interest since it was shown that the spread and prognosis of primary tumors is correlated with their vascularization (N. Weidner, J. P. Semple, W. R. Welch, and J. Folkman, N. Engl. J. Med., 324: 1-8, 1991). Basic fibroblast growth factor (bFGF) and its high-affinity receptor FGFR-1 have been implicated in melanoma growth and angiogenesis (R. Halaban, Y. Funasaka, J. Lee, J. Rubin, D. Ron, and D. Birnbaum, Fibroblast Growth Factors in Normal and Malignant Melanocytes, pp. 232-243. New York: The New York Academy of Sciences, 1991). We have studied the expression of the Tie endothelial cell receptor tyrosine kinase mRNA in skin and primary cutaneous melanomas as well as in their skin and brain metastases by in situ hybridization. The Tie probe hybridized very weakly with the vascular endothelium of capillaries of normal skin, while it was detected in larger arteries and veins as well as in capillaries around sweat glands. However, capillaries and medium sized vessels within cutaneous and brain metastases of melanoma were strongly positive for Tie mRNA. In contrast, endothelial cells contained very little or no FGFR-1 transcripts, whereas abundant FGFR-1 mRNA was present in melanoma tumor cells and in fibrovascular stroma. In agreement with these findings, a Tie specific amplified cDNA band was obtained by reverse transcription-polymerase chain reaction from melanoma metastases but not from normal skin. These results suggest a role for the Tie receptor in the angiogenesis associated with melanoma metastases. PMID- 7987858 TI - Long-term serum/plasma-free culture of human cytotoxic T lymphocytes induced from peripheral blood mononuclear cells. AB - Tumor-specific human cytotoxic T lymphocytes (CTL) were induced by co-culturing peripheral blood mononuclear cells with X-ray-irradiated human lung squamous carcinoma cells, SQ-5, in the medium supplemented with interleukin(IL)-1, IL-2, IL-4 and IL-6, and 5% autologous plasma for 3 or 5 days. The CTL grew in serum/plasma-free medium containing these four interleukins and 0.5% bovine serum albumin for over a month and maintained killing activity of target cells within 48 h at an effector/target ratio of 1.25. Their growth was essentially dependent on the target SQ-5 cells, which were renewed every 5 days. Under these conditions, IL-4 and IL-6 could be omitted. When anti-CD3 monoclonal antibody was added to the serum/plasma-free medium supplemented with IL-1 and IL-2, the target tumor cells were not required to maintain the specific killing activity of the CTL. A large number of CTL (10(11)) were obtained in 35 days. PMID- 7987859 TI - Circulating concentrations of interleukin-6 in cancer patients and their pathogenic role in tumor-induced hypercalcemia. AB - Circulating interleukin-6 (IL-6) concentrations correlate with disease activity in severe inflammatory conditions, in sepsis and in some hematological malignancies. On the other hand, IL-6 is a potent stimulator of osteoclastogenesis and has been implicated as a contributory factor in the genesis of osteopenic conditions. We measured circulating IL-6 levels by a sensitive (detection limit of 10 U/ml) and specific bioassay in 103 patients with advanced cancer, including 41 with tumor-induced hypercalcemia before any specific hypocalcemic therapy. We related IL-6 concentrations to clinical features and to biochemical parameters of bone metabolism, including blood Ca, Ca2+, Pi, intact parathyroid hormone, parathyroid hormone-related protein, osteocalcin, 1,25-(OH)2-vitamin D and, as markers of bone resorption, the fasting urinary excretion of calcium (Ca/creatinine) and hydroxyproline. IL-6 levels were increased, i.e. detectable, in 23% of the patients, 8/41 (20%) hypercalcemic and 16/62 (26%) normocalcemic patients (NS); the distribution of the values was similar in the two groups. The presence of increased IL-6 concentrations was not related to any clinical characteristic, notably not to the survival nor to the existence of bone metastases, whether in hypercalcemic or normocalcemic patients; e.g., only 3/12 (25%) hypercalcemic subjects without bone metastases had elevated IL-6 levels. We found no significant correlations between IL-6 concentrations and any of the biochemical parameters studied. Hypercalcemic subjects with increased IL-6 had higher urinary Ca/creatinine levels than patients with normal IL-6 levels (P < 0.005) but this was not the case in normocalcemic subjects. Mean concentrations of inflammatory or other bone metabolism markers were not significantly different between patients with normal or with elevated IL-6 levels. In summary, circulating IL-6 levels were increased in 23% of 103 patients with advanced cancer, but the frequency of increased IL-6 concentrations was not related to the presence of hypercalcemia or to any marker of calcium metabolism or bone turnover. The pathogenic importance of circulating IL-6 in patients with solid tumors remains to be demonstrated and our data indicate that increased circulating levels of IL-6, possibly reflecting the activation of the immune system, only contribute in a minor way to the osteolytic process in patients with tumor-induced hypercalcemia. PMID- 7987860 TI - Immunoendocrine mechanisms in mammary tumor progression: direct prolactin modulation of peripheral and preneoplastic hyperplastic-alveolar-nodule- infiltrating lymphocytes. AB - We have previously shown that the immunoregulatory function of prolactin may play a role in the progression of the mouse mammary preneoplastic hyperplastic alveolar nodule (HAN) line C4 to carcinoma. In this study we investigated the direct effect of prolactin on lymphocytes isolated from normal and C4-HAN-bearing mice. In addition, we tested the effect of ovariectomy on prolactin/lymphocyte interaction to see whether, as has been reported in rats [Mukherjee P., Hymer W. C. (1992) Prog Neuroendocrinol Immunol 5: 108; Viselli S. M. et al. (1991) Endocrinology 129: 983], removal of estrogen would enhance the response to prolactin in mice. Proliferation of splenocytes, lymph node cells and HAN infiltrating lymphocytes was stimulated by prolactin in a dose-responsive fashion. Ovariectomy did not alter this effect consistently. Cell-cycle analysis based on simultaneous staining of DNA and RNA revealed that prolactin-stimulated lymphocytes progress through all phases of the cell cycle whereas anti-prolactin antiserum inhibits this stimulation. Two-color flow-cytometric analysis revealed the time-dependent induction of interleukin-2 (IL-2) receptor expression on both CD4+ and CD8+ cells by prolactin. Prolactin-treated lymphocytes also produced low yet detectable levels of bioactive IL-2 in a dose- and time-dependent fashion. Prolactin enhanced lymphocyte responsiveness to mitogens and showed a marked synergism at suboptimal concentrations. Pretreatment of splenocytes from HAN bearers with a high concentration of prolactin slightly enhanced natural killer (NK) activity; anti-prolactin antiserum reduced the NK lytic activity of poly(I).poly(C)-activated splenocytes from HAN-bearing mice. Our results provide direct experimental evidence for the stimulatory effect of prolactin on lymphocyte function and IL-2-mediated lymphocyte proliferation and suggest a mechanism linking the endocrine system to immunomediated enhancement of HAN progression. PMID- 7987861 TI - Interactions between human macrophages and tumor cells in three-dimensional cultures. AB - Human blood mononuclear cells were cultured for 7 days in hydrophobic plastic bags. Macrophages differentiated from monocytes and purified by elutriation were then cocultured with round-shaped aggregates of epithelial cells (spheroids). Spheroids prepared from the SK-MES-1 carcinoma cell line were cultured individually, under constant stirring, in multiwell plates coated with agarose. Macrophage/spheroid interactions were investigated under various experimental conditions. Macrophages activated with interferon gamma aggregated to each other and to spheroids, in contrast to control unactivated macrophages. Histological examination, after staining with a macrophage-specific monoclonal antibody, showed that both control and interferon-gamma-activated macrophages migrated between epithelial tumor cells and infiltrated the spheroids. The addition of anti-ICAM-1 monoclonal antibody inhibited macrophage homotypic aggregation as well as aggregation to and penetration into spheroids. The macrophages did not exert cytolytic effects, as judged by a chromium-51 release assay, but provoked a diminution of tritiated thymidine incorporation by tumor cells. Cytostatic activity was observed with effector: target ratios as low as 1:16, and was maximal (99% at a 1:1 E:T ratio) with macrophages differentiated in the presence of granulocyte/macrophage-colony-stimulating factor. The cytostatic effect was not related to tumor necrosis factor alpha secretion. PMID- 7987863 TI - Immunotoxins to the HER-2 oncogene product: functional and ultrastructural analysis of their cytotoxic activity. AB - Two immunotoxins were prepared using monoclonal antibodies (mAb) directed towards two distinct epitopes of the gp185HER-2 extracellular domain, and the type I ribosome inactivating protein (RIP) plant toxin saporin 6. Cell protein synthesis inhibition assay reveals that the immunotoxins display a potent and specific cytotoxicity that is characterized by a slow rate, since the time required to inhibit incorporation of radiolabeled leucine completely ranges from 36 h to 60 h depending on the target cell line and the immunotoxin. Because this feature may hamper the immunotherapeutic use of these conjugates we analysed this further by studying the early phases of internalization of immunotoxins by immunoelectron microscopy. The results of this study have demonstrated that the distribution pattern of the immunotoxins and of the unconjugated mAb over the cell surface overlaps. Similarly the mAb and immunotoxins are internalized into the cell by two different pathways: via clathrin-coated pits or via smaller uncoated pits and vesicles. A higher degree of internalization is achieved when the two immunotoxins are used in combination. Unlike the slow kinetics of cell intoxication the process of immunotoxin endocytosis is characterized by a rapid rate of internalization (above 40% at 5 min in the SK-BR-3 cell line). Although these findings provide no clue to explain the mechanisms of the slow rate of cytotoxicity of the two immunotoxins their rapid internalization indicates that these reagents can be exploited in immunotherapeutic approaches to gp185HER-2 expressing malignancies. PMID- 7987862 TI - Development of four donor-specific phenotypes in human long-term lymphokine activated killer cell cultures. AB - A series of 62 lymphokine-activated killer cell (LAK) cultures from 44 different donors was investigated for the distribution of various CD markers during a cultivation period of 3 weeks. Great differences in the phenotypic pattern were found between different donors, but similar changes of the subset pattern of various donors allowed a classification of the LAK cultures into four distinct LAK types. LAK type 1 was characterised by low numbers of CD3+ cells and high values for CD56+ cells. In LAK type 2 cultures gamma/delta TCR+ cells extensively proliferated, whereas in LAK type 3 cultures the CD57 and CD8 values increased considerably. LAK type 4 cultures did not show any of these characteristics. The resulting phenotype of a LAK culture was donor-specific, as LAK cultures established from the same peripheral blood mononuclear cells (PBMC), fresh or after cryopreservation, or from PBMC obtained from the same donor at different venous punctures, always developed the same phenotype. A clear correlation between phenotype and killing activity could only be found for LAK type 1 cultures, which always developed high lytic activity. Long-term IL-2 stimulation induced high levels of perforin-positive cells in LAK cultures but the perforin content did not correlate with the cytotoxicity. The transcription pattern for various cytokines only varied slightly between the cultures. Messenger RNA for granulocyte/macrophage- colony-stimulating factor, interferon gamma, tumour necrosis factor alpha, interleukin-4 (IL-4) and IL-5 were found in almost all cultures during the entire cultivation period, whereas mRNA for IL-2 was never detected. Most variations in the transcription pattern were observed for IL-6 and IL-7. However, no correlation could be found between the endogenous cytokine production and the phenotype or lytic activity of the LAK cultures. Further studies are required to determine the factors that cause lymphocyte subsets from a specific donor to proliferate preferentially under long-term IL-2 stimulation. PMID- 7987864 TI - The fate of antibodies and their radiolabels bound to tumor cells in vitro: the effect of cross-linking at the cell surface and of anti-idiotype antibodies. AB - In order to obtain rapid blood clearance of circulating antibodies (Ab) at a desired time, cross-linking reagents such as second Ab are often employed. Such reagents will generally bind to Ab located at the tumor site as well as free Ab, and we therefore investigated whether the cross-linking of Ab bound to the surface of tumor cells affects the processing of those Ab. Cross-linking was induced in various ways: a polyclonal second Ab [rabbit anti-(mouse IgG)], a monoclonal rat anti-(mouse IgG constant region) Ab, and streptavidin used in conjunction with a biotinylated first Ab. Processing was followed for 3 days, to allow nearly all of the bound Ab to reach its ultimate fate. Results depended strongly on the particular first Ab used. Two basic effects were observed. First, the second Ab efficiently prevented the early dissociation of intact Ab from the cell; once the second Ab bound, there was virtually no dissociation of the primary Ab bound to the cells. For most Ab, where only a small proportion of bound Ab dissociated intact, this effect was relatively small. However, for an unusual Ab, where the majority dissociated intact (L6) the effect of a second Ab in prolonging Ab retention by the cell was dramatic. Second, cross-linking sometimes resulted in markedly accelerated internalization and degradation of the bound Ab, coupled with the release of degradation products into the medium. This process resulted in much shorter retention of the radioisotope by the cell. If a "residualizing" radiolabel was used, 125I-dilactitoltyramine, which is probably trapped within lysosomes after Ab catabolism, the effect of the second Ab in accelerating loss from the cell was largely prevented. We also tested anti idiotype Ab as cross-linking reagents. In addition to testing anti-idiotype Ab known to react with the cell-bound primary Ab, we also tested anti-idiotype Ab not expected to bind to cell-bound Ab, initially as a negative control. Unexpectedly, all anti-idiotype Ab tested induced rapid release of the primary Ab from the cell. This effect was similar to the effect of a large excess of unlabeled Ab, and we attribute it to the blocking of the free binding site of a "wobbling" Ab, which prevents its rebinding to a second antigen molecule. We conclude that the use of selected anti-idiotype Ab to clear circulating Ab, while not reacting with cell-bound Ab, must be done cautiously.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 7987865 TI - Human anti-(murine Ig) antibody responses in patients with hepatocellular carcinoma receiving intrahepatic arterial 131I-labeled Hepama-1 mAb. Preliminary results and discussion. AB - Human anti-(murine Ig) antibody (HAMA) responses were monitored in 32 patients with unresectable hepatocellular carcinoma (HCC) undergoing radioimmunotherapy using 131I-labeled anti-HCC monoclonal antibody (Hepama-1 mAb) intrahepatic arterial infusion. Dosages of Hepama-1 mAb ranged from 5 mg to 20 mg and the mAb was radiolabeled with 0.74-4.00 GBq (20-108 mCi) 131I (4-6 mCi/mg). T lymphocyte subsets were examined before and after radioimmunotherapy in 24 patients. In this series, 34.4% (11/32) of patients developed HAMA within 2-4 weeks after the infusion. All patients with a negative HAMA response (n = 14), had CD4+ T lymphocyte subsets (T helper/inducer) much lower than those of the HAMA-positive (n = 10) patients and the control group (n = 40) (P < 0.01) prior to infusion. The sequential resection and survival rates in the HAMA-negative group were also lower than that of the HAMA-positive group. Thus, the determination of T lymphocyte subsets might help to predict the HAMA response in HCC patients during radioimmunotherapy. PMID- 7987866 TI - Lack of cell-cycle-specific effects of recombinant tumor necrosis factor in vivo. AB - Several in vitro studies have demonstrated that tumor cells arrested in the G2 and M phases of the cell cycle expressed an increased sensitivity to the tumor necrosis factor (TNF). The scope of the present study was to investigate whether this cycle dependence of TNF effects also exists in vivo. The experiments were performed by using the Lewis lung carcinoma (LLC), which had been allotransplanted to nude mice. In order to induce delays of the tumor cell cycle in G2, the animals were treated with etoposide (40 mg/kg body weight i.p.) or with local radiation (15 Gy), each increasing the G2 fraction of the LLC from 10% to 35% and 50% respectively. For combination therapy with recombinant (r)TNF, the tumor was transplanted to four groups of six mice each, one of them serving as a control group the others being treated either with a G2 inductor alone, with rTNF alone, or with rTNF and a G2 inductor combined. Administration of rTNF (125 or 250 micrograms/kg body weight i.v.) was always carried out 24 h after therapy with etoposide or radiation when the maximum of G2 accumulation had developed. The growth behavior of the treated tumors revealed that the response of the LLC to rTNF in vivo was not improved by pretreatment with a G2 inductor and, thus, obviously lacked cell-cycle specificity. It is supposed that direct interactions of TNF with the tumor cells, which are a basic requirement for cell-cycle-linked phenomena, play a minor role in the therapeutic outcome of the LLC under in vivo conditions. PMID- 7987867 TI - Recruitment of helper T cells for induction of tumour rejection by cytolytic T lymphocytes. AB - Immunotherapy of cancer could be possible in cases in which competent effector T cells can be induced. Such an approach depends on expression of tumour-specific antigens by the tumour cells and on the availability of sufficient costimulatory support for activation of cytotoxic T lymphocytes. Here, a strategy for helper T cell recruitment for induction of tumour-specific cytotoxic immune responses is presented. Allogenic MHC class II molecules were introduced into tumour cells by cell fusion. These hybrid cells, when injected into mice, induced rejection of an established tumour. The contribution of CD4-expressing helper T cells in the induction phase and of CD8-expressing T cells in the effector phase of the immune response was demonstrated. The approach described could be applicable to cases in which a suitable tumour antigen is present but not identified; it employs regulatory interactions that govern physiological immune responses and is designed to be minimally invasive. PMID- 7987868 TI - Patient characteristics in cases of chronic severe heart failure with different degrees of left ventricular systolic dysfunction. AB - It has not been determined previously whether patients with severe chronic congestive heart failure differ in demographic characteristics with respect to left ventricular systolic dysfunction (LVD). In patients with severe chronic congestive heart failure in NYHA IV, an optional protocol in the CONSENSUS-I trial was designed to ascertain whether there were any differences in patient characteristics regarding the degree of LVD defined as left ventricular fractional shortening (FS). A subgroup of 54 patients from the CONSENSUS-I trial were evaluated with M-mode echocardiography. Patients with FS above median (14%) were older (74 +/- 7 vs. 68 +/- 7, p < 0.01), more often female (48 vs. 15%, p < 0.05) and had lower heart rates (77 +/- 15 vs. 95 +/- 17, p < 0.01). Analysis of the 2-year follow-up from the end of the trial was also performed. In the placebo group, patients with FS > 14% had significantly better prognosis than patients with FS < 14%. In the enalapril-treated group no such difference in survival was seen. The difference between the original treatment groups remained, despite the fact that treatment with enalapril was then made available to all surviving patients. In conclusion, patients with advanced chronic congestive heart failure and less severe LVD have different demographic characteristics than patients with more severe LVD. In the placebo group, but not in the enalapril group, prognosis was better in patients with less severe LVD. PMID- 7987869 TI - Amyloid deposits inside myocardial fibers in transthyretin-Met30 familial amyloidotic polyneuropathy. A histological and biochemical study. AB - A case of severe cardiac involvement is reported in a patient affected with familial amyloidotic polyneuropathy due to the Portuguese type I variant (Val- >Met30) of the transthyretin (prealbumin) molecule. Echocardiographic and hemodynamic studies suggested the presence of a progressive infiltrative cardiomyopathy that was later confirmed by endomyocardial biopsy. Amyloid deposits were found in both intra- and extra-myofiber location and thought to be related to primary involvement of the heart. Norepinephrine content of myocardial bioptic specimens was about threefold lower than normal, indicating that autonomic denervation may contribute to the maintenance and progression of cardiomyopathy. A sample obtained from the sural nerve showed a loss of myelinated fibers along with accumulation of amyloid masses in the endoneurial space. This histopathologic pattern correlated with a sharp decrease in the activity of the enzyme subserving electrochemical conduction through the axonal membrane, Na+, K(+)-ATPase. PMID- 7987870 TI - Endothelin concentrations in coronary sinus during atrial pacing-induced myocardial ischemia. AB - To investigate the possible role of endothelin in coronary vasoconstriction contributing to the development of myocardial ischemia, plasma endothelin concentrations at rest and during atrial pacing-induced myocardial ischemia have been measured in blood samples drawn from the aorta and coronary sinus in 12 patients with significant narrowing of the left anterior descending coronary artery. The plasma endothelin concentrations at rest were similar in the aorta (AO/R) and coronary sinus (CS/R) (4.8 +/- 2.4 and 4.5 +/- 1.7 pg/ml, respectively), the difference between coronary sinus and aorta plasma endothelin concentration (CS/R-AO/R) being -0.3 +/- 1.7 pg/ml. During atrial pacing-induced myocardial ischemia aortic plasma endothelin concentration (AO/P) did not change (4.6 +/- 2.6 pg/ml) and only an insignificant increase in the plasma endothelin concentration in the coronary sinus (CS/P) was observed (5.3 +/- 2.8 pg/ml). The difference between coronary sinus and aortic endothelin plasma concentration (CS/P-AO/P) was 0.6 +/- 2.5 pg/ml. Finally, the difference in endothelin concentrations between coronary sinus and aorta rose only insignificantly during pacing as compared to the resting values ([CS/P-AO/P]-[CS/R-AP/R] being 0.9 +/- 3.2 pg/ml). Thus, atrial pacing-induced myocardial ischemia in patients with significant left anterior descending coronary artery stenosis was not accompanied by significant changes in coronary sinus plasma endothelin concentrations.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7987871 TI - Myocardial blood flow rate and capillary permeability for 99mTc-DTPA in patients with angiographically normal coronary arteries. Evaluation of the single injection, residue detection method with intracoronary indicator bolus injection and the use of a mobile gamma camera. AB - The aims of the present study were to quantitate myocardial perfusion and capillary permeability in the human heart by means of the single-injection, residue detection method using a mobile gamma camera. With this method, the intravascular mean transit time and the capillary extraction fraction (E) can be determined in one experiment and in the same myocardial region. Eighteen patients with a history of chest pain episodes and angiographically normal coronary arteries were studied after intracoronary bolus injections of 99mTc-DTPA during elective coronary angiography. Two measurements were performed at a 15-min interval during resting conditions, and a third measurement was made during atrial pacing. Regions of interest were drawn in the left anterior descending (LAD) and the circumflex (CX) coronary artery perfusion beds. Sources of variation in plasma flow rate (fpl), E, and the calculated capillary permeability area product (PS) were determined. Spontaneous 15 min variations (mean of two values) for the LAD and the CX territory, respectively, gave a mean fpl(LAD) of 74.2 (measurement 1) and 77.8 ml.(100 g.min)-1 (measurement 2) (SD of the difference 7.5 ml.(100 g.min)-1) and fpl(CX) of 82.7 and 92.1 ml. (100 g.min)-1, respectively (SD of the difference 16.1 ml.(100 g.min)-1), and E(LAD) was 51.0 and 55.7%, respectively (SD of the difference 8.4%), and E(CX) was 52.9 and 50.4%, respectively (SD of the difference 5.9%). During atrial pacing, the rate pressure product increased by 97%, and in the LAD area fpl increased by 46% (p < 0.05), E decreased by 6% (NS), and PS increased by 39% (NS), whereas in the CX region flow increased by only 9% (p < 0.01), E decreased by 15% (p < 0.05), and PS decreased by 15% (NS) compared with baseline values. Both the spontaneous variation and the observer variation are low. The reduced vasodilator response in the CX region in combination with the decrease in E, which reduce the supply of nutrients, may play a role in the symptoms of these patients. PMID- 7987872 TI - Silent cerebral infarction associated with coronary artery disease. AB - To investigate the relationship of coronary artery disease and silent cerebral infarction, 50 patients who underwent coronary arteriography and cranial magnetic resonance imaging were studied. The patients were divided into three groups. The incidence of silent cerebral infarction (chiefly lacunar infarction) was significantly higher in patients with old myocardial infarction and in those with angina pectoris than in the control group (80, 78 and 29%, respectively, p < 0.05). Silent cerebral infarction is considered to be a risk factor for symptomatic cerebrovascular disease, so more attention should be focussed on the prevention of stroke in patients with coronary artery disease. PMID- 7987873 TI - Relaxation within the left ventricular myocardial wall. AB - To evaluate relaxation mechanics in the wall of the left ventricle needle mounted miniature pressure transducers were inserted at the subendocardial (ENDO) and subepicardial (EPI) level of the anterior wall of the left ventricle during acute open-chest experiments in 10 mongrel dogs. Pressures were recorded during control, volume load and after verapamil administration. The relaxation time constant (tau) was determined by fitting a monoexponential with offset to the isovolumic relaxation period of the ENDO, EPI and left ventricular pressure (LVP) tracings: p = p0e-t/tau + p1. Mean tau-values for LVP, ENDO and EPI during control were (mean +/- 1 SD, ms): 38 +/- 5, 60 +/- 12, 83 +/- 5; during volume overload: 55 +/- 10, 72 +/- 20, 85 +/- 31 and after verapamil administration: 58 +/- 13, 60 +/- 17 and 73 +/- 15, respectively. Relaxation time constants of ENDO and EPI were significantly longer than those of LVP during control and volume loading but not after verapamil when only EPI was significantly different from LVP. These results demonstrate that relaxation indices obtained from LVP may not always reflect intramyocardial mechanics. PMID- 7987874 TI - Wavelength index: a predictor of the response to disopyramide in paroxysmal lone atrial fibrillation. AB - We investigated whether the new parameter wavelength index could predict the response to chronic disopyramide therapy in patients with paroxysmal atrial fibrillation (AF). Twenty-seven patients with AF underwent electrophysiologic studies and the wavelength index was determined before and after intravenous administration of disopyramide. Then all patients were treated with oral disopyramide for 6 months. In 17 patients, AF was eliminated (group A), while it persisted in another 10 patients (group B). The ratio of the wavelength index before and after intravenous disopyramide was higher in group A than in group B. Thus, the wavelength index proved useful for predicting the response of AF to disopyramide. PMID- 7987875 TI - Change in left ventricular diastolic filling patterns in patients with supraventricular tachycardia treated by radiofrequency ablation: a Doppler echocardiographic study. AB - To evaluate changes in left ventricular diastolic filling patterns resulting from radiofrequency ablation for supraventricular tachycardia (SVT), 44 patients with SVT undergoing radiofrequency ablation (study group), and 16 patients with SVT undergoing electrophysiologic study without ablation (control group) were studied by pulsed Doppler echocardiography. Peak early diastolic filling velocity (E), peak atrial filling velocity (A), and an E/A ratio were obtained from the transmitral flow velocity pattern before and 24-48 h after ablation or electrophysiologic study. In the study group, E and E/A ratio decreased from 67 +/- 16 and 1.26 +/- 0.42 to 61 +/- 16 cm/s and 1.09 +/- 0.39 (p < 0.001), respectively. In the control group, only E/A ratio decreased from 1.40 +/- 0.47 to 1.26 +/- 0.44 (p < 0.001). Heart rate increased from 71 +/- 10 to 80 +/- 10 beats/min (p < 0.001) in the study group and from 67 +/- 8 to 72 +/- 10 beats/min (p < 0.05) in the control group. E and E/A ratio decreased significantly from 73 +/- 17 and 1.35 +/- 0.49 to 60 +/- 18 cm/s and 0.96 +/- 0.40 (p < 0.001) in patients with heart rate change of > 20% after ablation. E, A, and E/A ratio did not change significantly in patients with heart rate change of < 10% and of between 10 and 20% after ablation. Blood pressure and left ventricular ejection fraction did not change in either the study or control groups. It was concluded that left ventricular ejection fraction and Doppler diastolic filling patterns are unaffected by radiofrequency ablation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7987876 TI - Factors affecting the postoperative exercise capacity of patients with mitral stenosis and aortic regurgitation. AB - Factors affecting the exercise capacity of patients with mitral stenosis (MS) and aortic regurgitation (AR) are incompletely understood. Accordingly, exercise capacity was assessed in 13 patients with MS and in 13 with AR by means of cardiopulmonary exercise testing before as well as 3, 6 and 12 months after valve replacement. Left- and right-ventricular function were evaluated echocardiographically. Both in MS and in AR exercise capacity expressed by maximal oxygen consumption (VO2max) increased significantly after valve replacement and was directly related to right ventricular (RV) function assessed by the ratio of RV acceleration time to RV ejection time (r = 0.87, p < 0.001 and r = 0.74, p < 0.001, respectively) and inversely related to left atrial diameter (r = -0.72, p < 0.001 and r = -0.76, p < 0.001, respectively). No relation between VO2max and resting left-ventricular function was found. Thus, the postoperative improvement in the exercise capacity both in mitral stenosis and in aortic regurgitation is associated with an improvement in right-ventricular function and a decrease in left-atrial size. PMID- 7987877 TI - Efficacy of pulmonary artery banding in the prevention of pulmonary vascular obstructive disease. AB - In 57 nonconsecutive pediatric patients (mean age: 2.6 months) with shunt-related pulmonary hypertension, the efficacy of pulmonary artery banding (PAB) was analysed retrospectively with special reference to the development of pulmonary vascular obstructive disease (PVOD). The patients were grouped in accordance to morphology, hemodynamics and incidence of PVOD. Efficacy of PAB was assessed by pulmonary to systemic pressure, flow and resistance ratios obtained by heart catheterization performed pre- and postoperatively. PAB was very effective in 49 out of 57 patients (= 85.9%), in 8 cases a progression or possible progression of PVOD must be suggested. Only Down syndrome can be considered as a predisposing factor for the development of PVOD. Based on our results we conclude that PAB is a high effective procedure in the prevention of PVOD; however, despite the surgical effectiveness of PAB, PVOD can occur. Strict post-PAB examination of pulmonary flow and resistance parameters is recommended and the definite surgical repair should be performed as early as possible. PMID- 7987878 TI - Effects of percutaneous transluminal coronary angioplasty on late potentials and high frequency mid-QRS potentials. AB - The high frequency mid-QRS potentials and late potentials are important in coronary artery disease because they are related to the extent of ischemia and prognosis. In this study, the effects of successful percutaneous transluminal coronary angioplasty (PTCA) on these potentials were evaluated. Twenty-four patients with coronary artery disease (aged 34-67 years, 5 women, 19 men) were examined. Eight of these patients had a history of myocardial infarction (4 anterior, 3 inferior, 1 anterior and inferior). Signal averaged ECG was recorded at 40- to 250-Hz frequency ranges for late potentials and 150- to 250-Hz frequency ranges for mid-QRS potentials before PTCA, and they were repeated 1 month later. The QRS duration (107.7 +/- 9.8 to 105.3 +/- 9.3 ms, p < 0.0001) root-mean-square voltage (39.4 +/- 20.1 to 47.7 +/- 22.2 microV, p < 0.00001) and low amplitude signal duration (30.7 +/- 9.9 to 27.7 +/- 9.3 ms, p < 0.001) showed significant changes in 40- to 250-Hz ranges before and after PTCA. The same results were also obtained in the 150- to 250-Hz frequency ranges: the QRS duration decreased (90.9 +/- 9.8 to 86.5 +/- 9.1 ms, p < 0.005) and the root-mean square voltage increased (5.5 +/- 1.6 to 6.1 +/- 1.8 microV, p < 0.00001). Thus, successful PTCA causes improvement in late potential parameters, so the risk of malign arrhythmia that affects the prognosis can be reduced. Additionally, the increase in high frequency mid-QRS potentials shows the decrease in the ischemia after PTCA. PMID- 7987879 TI - Total coronary artery occlusion late after successful coronary angioplasty of moderately severe lesions: incidence and clinical manifestations. AB - Coronary restenosis after balloon angioplasty is a slow process that develops over a few months. In some patients, with an initially successful angioplasty, an artery that originally had only moderate stenosis becomes totally occluded as a result of restenosis. This report describes 16 such patients out of 415 dilated lesions with late angiographic follow-up. Ten patients presented with stable angina pectoris, 5 had unstable angina and only one was admitted with a small myocardial infarction. Visible collaterals were present in 15 patients. Except for the patient who sustained myocardial infarction, none of the late angiograms showed the typical morphological features of acute lesion. We conclude that total coronary occlusion late after successful angioplasty of an artery that was moderately narrowed is rare. The 'restenotic' occlusion is a slow process that stimulates collateral formation and thus the risk of myocardial infarction is small. PMID- 7987880 TI - Predictors of coronary dissection following percutaneous transluminal coronary balloon angioplasty. AB - To determine predictors of acute coronary dissection after coronary angioplasty, we studied 170 consecutive patients who underwent arterial dilatations of 234 arteries. Coronary dissection occurred in 103 (44%) arteries. More dissections occurred in women [40/73 (55%) versus 63/161 (39%), p < 0.03] and in patients with long lesions [45/74 (61%) versus 56/158 (35%), p < 0.0005]. Balloon/arterial diameter ratio was higher in patients with dissection (1.1 +/- 0.2 versus 1.0 +/- 0.2, p < 0.02). Complications did not differ in patients with and without dissection except for non-Q wave myocardial infarctions which were more frequent in patients with coronary dissection [10/12 (83%) versus 2/12 (17%), p < 0.01]. Thus coronary dissection during angioplasty is relatively frequent. However, most dissections are not associated with complications. Balloon dilatation of lesions in female patients and in patients with long lesions are more likely to result in dissection. PMID- 7987881 TI - Doppler diastolic transmitral flow patterns in severe heart failure: response to controlled changes in filling pressure using intravenous isosorbide dinitrate. AB - Serial Doppler diastolic transmitral flow patterns were compared with simultaneous hemodynamic measurements in a homogeneous group of patients with severe (New York Heart Association class 4) heart failure who were receiving high dose (508 +/- 271 micrograms/min) intravenous isosorbide dinitrate. The Doppler tracing uniformly showed a severe restrictive pattern, with tall peak early diastolic filling (E) wave (84 +/- 12 cm/s), small late filling (A) wave (28 +/- 8 cm/s) and very high E/A ratio (3.2 +/- 0.8). Isosorbide dinitrate decreased wedge pressure and systemic vascular resistance by a third and increased cardiac index by more than 40%. Transmitral Doppler E/A ratio changed directly in relation to the changes in pulmonary capillary wedge (r = 0.85, p = 0.03) and right atrial pressure (r = 0.84, p = 0.03), indicating preload dependence of transmitral flow velocity, even in severe heart failure. PMID- 7987882 TI - Comparative efficacy and tolerability of 5 and 10 mg simvastatin and 10 mg pravastatin in moderate primary hypercholesterolemia. Simvastatin Pravastatin European Study Group. AB - Simvastatin and pravastatin, two 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors, were compared in a multinational, randomized, double-blind trial. Patients demonstrating moderate hypercholesterolemia after 10 weeks on a lipid lowering diet received 6 weeks of treatment with 5 mg/day simvastatin (n = 143) or 10 mg/day pravastatin (n = 138); the simvastatin dose was increased to 10 mg for an additional 6 weeks while the pravastatin dose remained at 10 mg. When administered at lower or equivalent daily doses, simvastatin was significantly more effective than pravastatin in reducing total and low-density lipoprotein (LDL) cholesterol. Reductions in plasma total and LDL cholesterol were significantly greater with 5 mg simvastatin (16 and 23%) compared to 10 mg pravastatin (12 and 18%; p < or = 0.01). The efficacy of 10 mg simvastatin in lowering these lipid parameters was also superior (19 vs. 11% and 27 vs. 17%, respectively; p < or = 0.01). At 6 and 12 weeks, a significantly higher percentage of simvastatin patients (45 and 59%, respectively) achieved a desirable LDL cholesterol level of < 130 mg/dl (< 3.4 mmol/l) compared to pravastatin patients (32-33%; p < or = 0.05). Both drugs were well tolerated and had comparable safety profiles. PMID- 7987883 TI - Disappearance of a syndrome: Dressler's syndrome in the era of thrombolysis. AB - The incidence of the post-myocardial infarction syndrome (Dressler's syndrome) among thrombolized patients has not been established yet. To clarify this issue we prospectively studied 201 consecutive patients with acute myocardial infarction who had undergone recombinant tissue-type plasminogen activator therapy followed by 5 days of heparin administration. All patients were followed for at least 3 months for clinical signs of Dressler's syndrome. None of the 148 patients (76%) who showed clinical signs of early reperfusion had Dressler's syndrome. The sole patient in the group who manifested the syndrome developed it 3 weeks following extensive anterior myocardial infarction with no evidence of reperfusion. Although 4 patients manifested signs of early pericarditis, none developed the syndrome. We conclude that Dressler's syndrome has in fact been rendered a rare phenomenon among patients who benefit from thrombolytic therapy. PMID- 7987884 TI - Ten-year mortality of patients admitted to coronary care units with and without myocardial infarction. Risk factors from medical history and diagnosis at discharge. DAVIT-Study Group. Danish Verapamil Infarction Trial. AB - The purpose was to evaluate the 10-year mortality in patients with acute chest pain suspected of myocardial infarction with (AMI) and without (non-AMI) confirmed diagnosis and to determine risk factors from the medical history and the diagnosis at discharge. One-thousand eight-hundred and ninety-seven non-AMI patients and 1,401 patients with AMI consecutively admitted to 1 of 16 coronary care units participating in The Danish Verapamil Infarction Study were included. During follow-up, 630 deaths occurred among the non-AMI patients and 415 of these could be classified as cardiac deaths. Multivariate analysis identified the following risk factors containing independent prognostic information about mortality for non-AMI patients: age, previous AMI, sex, and diabetes. In patients with AMI the risk factors were: age, previous AMI, clinical heart failure, diabetes, and angina pectoris. By including the diagnosis at discharge for non AMI patients in the Cox analysis, the prognostic significance was compared to the variables from the medical history. Only the diagnoses bronchopneumonia, musculoskeletal disorders and observatio sine indicatione therapiae added independent prognostic information. We conclude that non-AMI patients are at high risk for mortal events in the long term. High-risk patients can be identified from their medical history, whereas the diagnosis at discharge only adds limited prognostic information. All non-AMI patients should be carefully evaluated regarding coronary artery disease at the time of discharge in order to improve the risk stratification, treatment and prognosis. PMID- 7987886 TI - Waterborne microorganisms: colonization, contamination, and disease potential- Part 1. PMID- 7987885 TI - Doppler echocardiographic assessment of left ventricular diastolic function in patients with systemic lupus erythematosus. AB - Thirty patients with clinically inactive systemic lupus erythematosus (SLE) were examined by Doppler echocardiography to investigate the diastolic properties of the left ventricle. Twelve age-matched healthy women were also examined as controls. The pulsed wave transmitral Doppler flow velocity curves were digitized and curves of their first derivatives were obtained. Isovolumic relaxation time (IRT), acceleration and deceleration half-time of the rapid filling wave (E) and atrial contraction wave (A) (AHTe, DHTe, AHTa, DHTa), A/E, peak dE/dt, -peak dE/dt, peak dA/dt, -peak dA/dt were measured. In the SLE group, IRT and DHTe were prolonged, A, A/E, peak dA/dt and -peak dA/dt were increased compared with the control group. We conclude that patients with SLE have abnormal left ventricular diastolic function, even though their disease is clinically inactive. PMID- 7987887 TI - Metronidazole in periodontitis V: debridement should precede medication. AB - Two previous double-blind studies have shown that 1 week of metronidazole, plus scaling and root planing, can significantly reduce the number of teeth per patient that require periodontal surgery, when compared to a positive-control treatment that consisted of 1 week of placebo treatment plus scaling and root planing. The only difference between the two studies was that in one, metronidazole or placebo tablets were taken at the beginning of the debridement procedures, while in the other, the tablets were taken after all debridement was completed. This article describes the results obtained by combining the data from both studies and using an analysis of variance to identify the effects of medication and those of the study protocol. There was an average reduction in surgical needs of about 7.1 teeth per patient using metronidazole compared to 2.4 teeth in the positive-control group (P = 0.004). In the deep pockets, there was a significant protocol effect because there were additional improvements associated with using the medications after the debridement was completed. PMID- 7987888 TI - Management of a vascular lesion using arterial embolization: a case report. PMID- 7987890 TI - Managed care in the dental reimbursement environment--Part 1. PMID- 7987889 TI - Drug interactions in dental practice: a summary of facts and controversies. AB - The potential for drug interactions is a concern to all dentists. The issue is made even more imposing by the amount of scientific information published each month. It is not only important for dentists to be aware of interactions that have been established, but also those that are no longer tenable. Of particular concern are continued misconceptions about the antibiotic-oral contraceptive and the vasopressor-antidepressant interactions. This article will clarify these issues as well as highlight established interactions associated with those drug classes used most frequently in dental practices. PMID- 7987891 TI - Dentistry and the cancer patient: Part 1--Oral manifestations and complications of chemotherapy. AB - Chemotherapy is frequently used as a primary or adjunctive modality in the treatment of patients with cancer. As the incidence of cancer in the population increases, the ability to properly detect, diagnose, and treat oral side effects of chemotherapy becomes ever more important. Depending on the types and dosages of chemotherapeutic agents used, a wide range of oral complications may appear. This article, in two parts, reviews the potential oral manifestations associated with cancer chemotherapy and appropriate management techniques. PMID- 7987892 TI - Multimodal treatment of drug-induced gingival hyperplasia in a kidney transplant patient. AB - Medical advances for treating organ diseases have resulted in thousands of organ transplants being performed each year. Every patient receiving a transplanted organ will also be placed on drugs that may induce gingival hyperplasia as a side effect. This article discusses the multiphasic approach to treating the disfiguring hyperplasia through chemical and mechanical plaque control, surgical removal of the tissue by lasers, and postsurgical rinses with folate. PMID- 7987893 TI - Dental caries vaccines: science and status. AB - Dental caries, caused by the etiologic agent Streptococcus mutans, is considered the most common human infectious disease. Development of a vaccine has been under investigation for more than 25 years. Possible approaches include immunizing patients using an oral vaccine containing components of the causative bacterium and by intramuscular injection. Although both approaches have proved promising, several considerations have delayed further development of a vaccine. This article reviews the scientific results and status of the various vaccines. PMID- 7987894 TI - Cigarette smoking: a major risk factor for periodontitis. AB - Cigarette smoking is a risk factor for many diseases, and recent evidence indicates that it adversely affects periodontal health. A number of epidemiologic studies have shown strong associations between smoking and the prevalence and severity of periodontitis, as well as interproximal bone loss. Although the pathogenesis of periodontitis in smokers is poorly understood, there are data suggesting that smoking causes defects in neutrophil function, impaired serum antibody responses to periodontal pathogens, and potentially diminished gingival fibroblast function. The prevalence and severity of periodontitis in former smokers is decreased compared to current smokers, providing evidence that smoking cessation is beneficial. Smoking markedly influences response to treatment, and a subset of smokers predominates among refractory periodontitis patients who are resistant to conventional treatment. A patient's smoking history is a useful clinical predictor of future disease activity. Current estimates suggest that smoking is associated with a large proportion of periodontitis cases and constitutes a major public dental health problem. PMID- 7987895 TI - Diabetes mellitus and periodontal disease--a current perspective. PMID- 7987896 TI - Genetic risk factors for the periodontal diseases. PMID- 7987897 TI - HIV disease as a risk factor for periodontal disease. AB - A multitude of oral lesions, including unique forms of periodontal disease, have been discovered in individuals infected with the human immunodeficiency virus (HIV). Although the frequency of HIV-associated periodontal diseases appears to be less than previously thought, many researchers agree that an important factor influencing the prevalence of unique periodontal disease in the HIV population is the degree of immunodeficiency. The pathogenesis of HIV-associated periodontal diseases remains unclear, but may be the result of microbiota and/or alterations in the host. HIV-gingivitis, now called linear gingival erythema, and HIV periodontitis, now called necrotizing ulcerative periodontitis, have microbiology profiles similar to conventional adult periodontitis, although these lesions are quite different clinically. This article reviews clinical signs and symptoms, treatments, and the pathogenesis of HIV-related periodontal findings. It specifically focuses on the immuno-incompetence of HIV disease as a risk factor for periodontal disease. Because the caseload of acquired immunodeficiency syndrome patients will increase significantly in the future, the dental practitioner must be able to recognize and manage the periodontal lesions associated with HIV infection. PMID- 7987898 TI - Assessing bacterial risk factors for periodontitis and peri-implantitis: using evidence to enhance outcomes. AB - This article discusses the use of microbial diagnostics and their relationship to the treatment of periodontal and peri-implant disease. Clinical and microbiologic characteristics are described to help the practitioner recognize patients with periodontitis and peri-implant infections. By using available information (evidence) to guide the choice of therapeutic intervention, the clinician can enhance the outcomes resulting from therapy. PMID- 7987899 TI - Health care reform: what are the issues? PMID- 7987901 TI - Simplifying restorative options using angled hollow-cylinder implants. PMID- 7987900 TI - Familial transmission of periodontal pathogens as a risk factor for periodontal disease progression. PMID- 7987902 TI - Sjogren's syndrome: pathology, oral presentation, and dental management. AB - As one of the major autoimmune conditions involving the oral, head, and neck regions, Sjogren's syndrome has a significant level of dentally related pathology. As a result of salivary dysfunction, the teeth and mucosa may develop a wide array of changes. If these changes are not managed properly, major oral dysfunction can occur. An evaluation of salivary function, the management of xerostomia and its effects, dietary counseling, and an overall appreciation of the extraoral components of Sjogren's syndrome are presented. The dental component of comprehensive patient management is one of the most important aspects of this condition, with the dental practitioner being an essential part of the health-care team. PMID- 7987903 TI - The Flexi-Flange post system and its clinical use. PMID- 7987904 TI - Endodontic therapy on the mandibular second molar: easiest to treat of the difficult, molar teeth. AB - Molar teeth present more problems during endodontic therapy than do bicuspid or anterior teeth. The major reasons for this are that molars can have complicated canal systems with unexpectedly large numbers of teeth with four canals, and they often have quite curved canals, which are more difficult to prepare and fill. The mandibular second molar generally is the easiest of these difficult teeth to treat, but they do have some areas of complication, too. The mesial root almost always has two--not one--canals and a rarely described condition, the C-shaped canal system, may be present. PMID- 7987905 TI - Patient management in a tobacco-cessation program in the dental practice. AB - Smoking and smokeless tobacco can cause significant damage to the oral cavity, including life-threatening cancers. Consequently, dentists and their office staffs should and can play an influential role in advising their patients to quit using tobacco. The National Cancer Institute has developed the "Four A's" approach to tobacco-cessation counseling: (1) ask about tobacco use; (2) advise to quit; (3) assist with quitting; and (4) arrange for follow-up. With minimal expenditures of treatment time, the dentist and office staff can encourage patients to quit using tobacco through nonconfrontational messages that point out the clinical damage caused by smoking and smokeless tobacco. Besides behavior modification, dentists can prescribe several Food and Drug Administration approved pharmaceutical agents as adjuncts to a tobacco-cessation program. Nicotine polacrilex (gum) and nicotine transdermal systems have proven very useful in helping tobacco users quit their habit. PMID- 7987906 TI - Comparative antimicrobial effectiveness of a substantive (0.12% chlorhexidine) and a nonsubstantive (phenolic) mouthrinse in vivo and in vitro. AB - Antimicrobial mouthrinses can play an important role in maintaining oral health by killing cariogenic organisms and preventing plaque and gingivitis. The active ingredients are adsorbed by oral tissues and then gradually released into the saliva. In this article, the effectiveness of a substantive chlorhexidine and a nonsubstantive phenolic antimicrobial mouthrinse were tested. When compared, the results indicated that the two types of mouthrinses are equally effective at killing salivary microbes for up to 30 minutes after rinsing. The prescriptive substantive rinse, however, continued its microbicidal effect for a longer duration (up to 5 hours) than the over-the-counter nonsubstantive rinse. The substantive rinse showed pronounced and measurable zones of inhibition around each well in the agar diffusion assay where the nonsubstantive rinse showed no zone around any well at any time. The substantive rinse also showed a superior ability to inhibit the growth of 28 oral microbes, including some putative periodontopathogens, which were assayed. PMID- 7987907 TI - The impact of balloon material and lesion characteristics on the incidence of angiographic and clinical complications of coronary angioplasty. AB - To assess the importance of balloon material used for percutaneous transluminal coronary angioplasty (PTCA), we compared the complication rates observed with low complaint plastomer (PM 300), intermediately compliant polyethylene (PE 600), and highly compliant polyolefin copolymer (POC) balloons. In a total of 1,650 procedures, one of these balloon materials was used to dilate 2,040 lesions. The dissection rate tended to be slightly lower with the use of more compliant balloon material. The total clinical complication rate (death, emergency coronary surgery, myocardial infarction, need for bail-out stenting or for prolonged heparin treatment, abrupt out-of-laboratory vessel closure) was 8.1%, 7.4%, and 4.2% in the procedures exclusively performed with PM 300 (N = 653), PE 600 (N = 543) and POC (N = 454) balloons, respectively (P = 0.03). In multivariate analysis, the use of less compliant balloon material emerged as an independent correlate of clinical complications (P = 0.007). However, the predictive power of the lesion complexity (B2, C versus A, B1) was four times stronger. In contrast to current concerns, the use of compliant balloon material seems at least as safe as the use of less compliant material. PMID- 7987908 TI - Dog bones, dumbbells, and dissections: sizing up angioplasty balloons. PMID- 7987909 TI - Discordance in the predictors of mortality vs. those of ischemic complications following transcatheter coronary intervention. AB - Outcomes of percutaneous transluminal coronary angioplasty (PTCA) depend upon the skill of the angioplasty team and on the characteristics of the patient population. Comparisons of outcomes from different laboratories must take into account the latter. A discordance may exist between the baseline predictors of death in hospital following PTCA and those for periprocedural ischemia. Baseline clinical and procedural characteristics of 3,725 patients who underwent PTCA during 1991 and 1992 were compared with complications by multivariate analysis. The age of the patient and the occurrence of an MI within the previous 30 days were the most powerful independent predictors of death. Ischemic complications were not independently associated with these factors. Emergency CABG was associated independently with target lesion complexity and abrupt reclosure, with unstable angina or attempted saphenous vein graft dilatation. Thus, mortality may more directly reflect baseline clinical characteristics than the skill of operators in avoiding ischemic complications. PMID- 7987910 TI - Efficacy and safety of using perfusion dilatation catheter as initial balloon in coronary angioplasty. AB - The efficacy and safety in using a new low-profile perfusion balloon catheter (PBC) as the initial balloon in percutaneous coronary angioplasty (PTCA) was assessed retrospectively in 61 patients: 43 males, mean age 62 +/- 12 years. Thirty-three patients (54%) had unstable angina. PTCA was performed using an improved PBC in the following vessels: LAD 40%; CX 21%; RCA 24%. Lesion morphology was: Type A 21%; Type B1 18%; Type B2 40%; Type C 21%. Mean artery size was 3.01 +/- 0.53 mm. Mean PBC size was 3.14 +/- 0.45 mm. The mean number of inflations used was 2.85 +/- 2.0. The mean longest inflation was 415 +/- 213 sec and the total inflation time was 663 +/- 342 sec to a mean maximum pressure atmosphere of 7.85 +/- 2.0 bars. The number of balloons used per procedure was 1.2 +/- 0.44. In 50 patients (82%) only one balloon was used during the PTCA. PTCA was successful (< 50% diameter stenosis without major complications) in 60 patients (98.4%). Mean diameter stenosis at baseline was 82 +/- 9.5% and post angioplasty 13 +/- 10.6%. A mild intimal tear occurred in 6 patients (9.8%). A stent was implanted in 3 patients (4.9%) due to severe dissection. In hospital reocclusion occurred in one patient (1.6%). There were no deaths or emergency bypass surgery. A low profile PBC is safe and effective as an initial balloon in PTCA. It may reduce the number of balloons used and inflations per procedure. PMID- 7987911 TI - Relation between changes in severity of coronary artery stenosis and anginal patterns. AB - Although myocardial ischemia causes angina pectoris, angina and the severity of coronary artery stenosis in individuals do not correlate. However, changes in anginal status over time correlated with changes in the severity of coronary artery stenosis as determined by repeated coronary arteriograms has not been previously studied. Coronary arteriograms, done both at entry into the Program on the Surgical Control of the Hyperlipidemias (POSCH) and 3 years later, were blindly graded for changes in overall severity of coronary artery stenosis according to protocol by the POSCH Arteriography Review Committee. Arteriographic and clinical data from 376 control subjects (347 men, 29 women) were analyzed. There was no statistically significant relation over a long-term (3 year) period between the absence, presence, development, or disappearance of angina pectoris and changes in coronary artery stenosis severity as determined by coronary arteriography. PMID- 7987912 TI - Coronary angiography in patients with established coronary artery disease: how much does the angiogram help in assessing changes in symptoms? PMID- 7987913 TI - The technique and safety of transseptal left heart catheterization: the Massachusetts General Hospital experience with 1,279 procedures. AB - With the introduction of interventional procedures such as percutaneous mitral valvuloplasty and radiofrequency ablation of left-sided bypass tracts, there has been renewed interest in the technique of transseptal left heart catheterization. We review our experience with 1,279 transseptal catheterizations performed over the last 10 years. The most common indications for transseptal catheterization included direct measurement of left atrial pressure or access to the left ventricle in patients with prosthetic aortic or mitral valves, and in patients undergoing percutaneous mitral valvuloplasty. A total of 17 major complications occurred (1.3%), including cardiac tamponade (15 patients, 1.2%), systemic emboli (1 patient, 0.08%), and death secondary to aortic perforation (0.08%). We conclude that when performed by experienced operators, transseptal left heart catheterization is associated with low morbidity and mortality. PMID- 7987914 TI - Percutaneous transluminal coronary angioplasty of the left internal thoracic artery graft: a case report in a child. AB - A 9-year-old girl who had undergone previous coronary artery bypass surgery at the age of 3.5 years for stenoses of the left anterior descending and right coronary arteries resulting from Kawasaki disease presented with recurrent exertional angina. Stenosis was found at the anastomosis of the left internal thoracic artery to the left anterior descending artery. Percutaneous transluminal coronary angioplasty was successfully performed. This is the first reported case of percutaneous transluminal coronary angioplasty of an internal thoracic artery graft in a child. PMID- 7987915 TI - Internal mammary artery collateral to the external iliac artery: an angiographic consideration prior to coronary bypass surgery. AB - The role of routine selective angiography of the internal mammary artery prior to myocardial revascularization is controversial. We report a patient with coronary artery disease and peripheral vascular disease in whom the left internal mammary artery supplied blood flow to the left external iliac artery via a collateral network. Thus, selective angiography of the internal mammary artery did play a major role in the proper management of this patient who required coronary bypass surgery. A major potential postoperative complication of left lower extremity ischemia may have been prevented. PMID- 7987916 TI - Circumferential balloon rupture and catheter fracture due to entrapment in a calcified coronary stenosis. AB - We report a case of coronary angioplasty balloon rupture and catheter fracture within a calcified lesion, requiring emergency coronary bypass surgery. The entrapped catheter could not be removed at surgery. This case re-emphasizes the hazards associated with angioplasty of calcified lesions. PMID- 7987917 TI - Absent left circumflex coronary artery. AB - This is the first reported case of a coronary artery anomaly in which the left circumflex artery was absent. The lateral and posterior aspects of the left ventricle were supplied by a large diagonal artery and a very long right coronary artery which continued along the atrioventricular groove. PMID- 7987918 TI - Angiographic evidence of right coronary bridging. AB - Systolic constriction of the left anterior descending coronary artery is a well recognized angiographic and autopsy finding. The etiology of this phenomenon is an intramural course of the coronary artery. Even though there has been autopsy evidence of an intramural course of the right coronary artery, this rare finding has not been associated with systolic constriction, "bridging" on coronary angiography. There is evidence that strenuous exercise can induce ischemia in an intramural left coronary artery. We therefore present a case report of angiographic evidence of systolic constriction of the right coronary artery. PMID- 7987919 TI - Coronary stenoses with low translesional gradient and abnormal coronary reserve: physiologic results after angioplasty. AB - Clinically active but angiographically moderate coronary stenoses present a difficult problem for intervention, especially when such lesions have a low translesional pressure gradient and impaired coronary reserve. Physiologic data suggest some lesions can be safely deferred, whereas others may benefit from immediate intervention. PMID- 7987920 TI - Bailout techniques for failed coronary angioplasty using 6 French guiding catheters. AB - Coronary angioplasty (PTCA) through 6 French (F) guiding catheters is feasible, although acute or threatened closure following coronary artery dissections may occur. This report describes our experience with the treatment of suboptimal results in 13 patients from a population of 144 patients who had PTCA through 6F guiding catheters. Patients were treated with a new low profile autoperfusion catheter (ACS, Flowtrack40) or with Palmaz Schatz stents, advanced through 6F guiding catheters. PTCA was performed via the radial artery in 11 pts (85%) or via the femoral artery in two patients (15%). In two patients, (15%) PTCA was complicated by an dissection associated with complete loss of flow (TIMI 0) and a dissection was considered to lead to abrupt closure in the remaining 11 patients (85%), despite the presence of normal flow. A Flow-track40 perfusion catheter was successfully applied in three of four patients. In one patient a persisting dissection after restoration of flow by a perfusion catheter was treated with three Palmaz Schatz stents. Implantation of Palmaz Schatz stents was attempted as primary technique in nine patients. In one patient the stent could not cross a dissection in the proximal LAD via the radial artery. With an 8F system via the femoral artery, two stents could successfully be deployed with the stent delivery system. In another patient the stent could not be advanced across a subtotal residual stenosis in a tortuous left anterior descending coronary artery. Despite normal antegrade flow and emergency bypass surgery, this patient developed a non Q-myocardial infarction. In the remaining patients, the clinical course was uncomplicated.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7987921 TI - Iliocaval reconstruction with metallic stents. AB - Percutaneous stenting is now the preferred first line of treatment for occlusive lesions of the great veins. A case is presented in which multiple metallic stents were used to reestablish communication between the suprahepatic inferior vena cava and both iliac veins. The clinical result was satisfactory: venous claudication was relieved, and the progress of chronic venous insufficiency arrested. Stent implantation offers a minimally invasive therapeutic option even when extensive revascularisation is indicated. PMID- 7987922 TI - Percutaneous deployment of a polytetrafluoroethylene (PTFE) graft to repair a pseudoaneurysm produced by a graft to graft anastomotic dehiscence. AB - Arterial injuries, creating a pseudonauerysm or arteriovenous fistula have, in the main, been managed through surgical ligation of the involved segments, arterial reconstruction, embolization of the involved artery, and percutaneous placement of a stented graft [Marin ML, et al: J Vasc Surg 18:299-302, 1993]. This communication describes the percutaneous repair of a large popliteal pseudoaneurysm, created by dehiscence of the anastomotic suture line of a composite polytetrafluoroethylene (PTFE) femoropopliteal and a popliteal posterior tibial graft using a PTFE graft without stent assistance. PMID- 7987923 TI - Should we avoid ostial implantations of Wiktor stents? AB - Complications arising during stent implantations in coronary arteries have been reduced by technological progress and the accumulated experience of interventional cardiologists. Retrospective and prospective randomized studies with several types of stents are currently available and show improved short and mid-term results. Wiktor stent provides increased flexibility for ease of implantation particularly in curved lesions. However, the flexibility of the Wiktor stent is also associated with low resistance in the longitudinal axis. We report four cases (in 4 out of 6 ostial lesions treated and 4 out of 43 Wiktor stents implanted during a 9-month period) in which stents have become unraveled during procedures on ostial lesions (2 saphenous venous grafts and 2 native coronary arteries). Death occurred in one case and one patient was treated by emergency coronary bypass surgery. In three cases the distal extremity of the guiding catheter stretched the stent meshes during the final control angiograms, and in one case the stent was stretched during withdrawal of the deflated balloon into the guiding catheter. We believe that it is preferable to avoid using this stent in ostial lesions. PMID- 7987924 TI - Initial experience with an extendable and reusable probe balloon-on-a-wire dilatation catheter in multivessel coronary angioplasty. AB - The "probe" balloon-on-a-wire device is an excellent balloon catheter for traversing very tight stenoses. Extending the probe by transecting its proximal inflation hub and then linking it to an extension wire has further enhanced its utility, as a wire exchange can then be performed without loosing wire access across a dilated lesion. We now report a previously undescribed technique for reconstituting and reusing an extended probe. The probe is initially transected at its proximal end. It is then extended by connecting a "Linx" wire into the open central lumen of the probe's hypotube. An over-the-wire balloon dilatation system is then substituted, via a wire exchange using a probing catheter, for final definitive dilatation. The probe is then reconstituted in the following manner. The inflation hub of the probe is recreated by modifying a standard USCI Tuohy-Borst Y adaptor and attaching this to the transected probe hypotube. It is subsequently used for dilating other stenotic arteries during multivessel angioplasty. The utility of this method was demonstrated in 5 consecutive cases. All cases underwent successful dilatations. There were no complications. This initial experience would suggest that the probe can be reused quite safely and effectively. PMID- 7987925 TI - Quantitation of in vitro coronary artery calcium using ultrafast computed tomography. AB - Ultrafast computed tomography (UFCT) has the potential to quantify coronary hydroxyapatite (HAP). However, no definitive studies validating this technique are available. We constructed a human chest phantom model with coronary arteries represented by cylindrical holes containing: (1) calcium chloride solutions, (2) a block of HAP immersed in paraffin (without partial volume effect), and (3) HAP granules embedded in a gelatin matrix (with partial volume effect). We scanned this model to determine the relationship between measured CT number per voxel and density of the calcium per voxel. The relationships between CT number and concentration of calcium chloride was linear (r = 0.992 to 0.999). Using a commercially available standard bone mineral phantom, we were able to estimate the concentration of HAP to an accuracy from 94 to 97% when partial volume effects were absent. However, when partial volume effects were present, two methods of estimating HAP produced significant errors (1 to 384%, and 17 to 52%). We conclude that significant partial voluming errors degrade the accuracy of HAP quantitation and that further evaluation and corrections are needed before such quantitation is clinically applied. PMID- 7987926 TI - Is collateral vessel "collapse" for real? PMID- 7987927 TI - Assessment of vascular trauma by local delivery catheters. PMID- 7987928 TI - [Nootropic drugs and their action mechanisms in relation to the neuropathobiology of senile dementia. I. Neurotransmission disorders in the brain]. AB - The author presents a review of agents which are presently included in the category of nootropic drugs and comments the relations between the pharmaceutical research of new nootropic and progressing knowledge of the neuropathobiology of Alzheimer's disease, senile dementia and degenerative processes of aging brain in general. In Part I., several hypotheses are discussed which explain the biological substrate of senile cognitive decline by disturbed brain synaptic neurotransmission (cholinergic, monoaminergic, petidergic) and, at the same time, drugs are suggested which may exert regulatory action on these dysfunctions. PMID- 7987930 TI - [Hyperkinetic disorder--a new view? (Generalized resistance to thyroid hormone)]. AB - A psychiatric disorder well known for more than fifty years in children and adolescents has changed several times its name. Mild child encephalopathy, minimal (mild) cerebral dysfunction, impaired attention, hyperkinetic disorder. The cause is not known, there is, however, evidence of familial disposition. Symptoms of this disorder were fully manifested in patients with generalized resistance to thyroid hormone. The disease is due to a genetic mutation of the beta-thyroid receptor and characterized by a reduced response of the pituitary and peripheral tissue to thyroid hormone. The authors refer to the work of authors, who discovered the association between the hyperkinetic disorder and generalized resistance to thyroid hormone. PMID- 7987929 TI - [Depressive states in old age and their therapy--1983-1993 survey]. AB - According to results of the census of gerontopsychiatric patients, on June 30, 1993 there were 741 hospitalized patients. In the submitted paper the authors follow up data on 207 patients treated with antidepressants. In 73% endogenous depressions were involved another third of the patients suffered from reactive conditions, organic mental disorders and dependence. Coexistence of organic and affective syndromes was frequently encountered (44.4%); in the majority of the group three nad more somatic diseases were present concurrently. As to antidepressants, even after 10 years tricyclic antidepressants are frequently used; the most frequently used drug was dosulepine. Antidepressants of the second generation are also used (maprotiline, viloxazine), less frequently selective inhibitors of serotonin uptake were administered (SSRI) and reversible monoaminooxidase inhibitors (RIMA). As compared with 1983 in 1993 more rarely Amitriptyline was used and the authors found that the spectrum of antidepressants used was extended and that these drugs were used also in other disorders than depressions. PMID- 7987931 TI - [Prevention of psychogenic disorders of eating]. AB - The author draws attention to the necessity to prevent psychogenic disorders of food intake with regard to their increasing incidence, factors conditioning their genesis and development, the serious character of their sequelae and the chronic character of the disorder. In addition to health educational programmes focused in particular on problems of nutrition, lifestyle, overweight and reasonable ways of its reduction, the author emphasizes also the necessity of early intervention. PMID- 7987932 TI - [Comparison of 3 forms of psychosocial rehabilitation in patients with epilepsy]. AB - The submitted paper is based on experience 1. with enlisting epileptic patients in programmes for neurotic patients during hospitalization (1968 - 1983, a total of 20 patients), 2. an ambulatory psychotherapeutic group for epileptic patients only (period 1983 - 1989, a total of 41 subjects, i.e. 39 patients and two mothers of patients) and 3. a club for epileptic patients (1990 - 1993, a total of 56 subjects, incl. 44 patients and relatives, partners and friends). The majority of patients are not only treated at the neurological department but are also psychiatric patients. The author mentions also excursions made with patients who attend the club and on two arts exhibitions of work made by the patients. He presents also results and discusses positive and negative of these tested forms of psychosocial work. The advantage of the programme for neuroses is the relatively intensive action. The advantage of the ambulatory group is the possibility to discuss in detail specific problems of patients with epilepsy. The club is acceptable for a much wider circle of patients than the other two forms. The author recommends a combination of the described three procedure and the application of the widest possible range of other rehabilitation methods. PMID- 7987933 TI - [Research in psychotherapy]. AB - Psychotherapy is an empirical discipline and is therefore open to exact investigations which is one of the prerequisites of its further development. The beginnings of exact research are associated with the names of H. J. Eysenck and C. R. Rogers. The contemporary research based frequently on the generic model of psychotherapy whose authors are D. E. Orlinsky and K. J. Howard is concerned in particular with the effectiveness of psychotherapy; it compares the action of different procedures, deals with differentiated indications and "mechanisms" inducing changes. The most frequent research strategies are an experimental approach, comparative (correlating) research and intensive research strategy. The most important source of information on research are meta-analyses which make it possible to summarize and compare an unlimited amount of mutually independent investigations. The hitherto most extensive meta-analytic processing of research projects was implemented in the Institute of Psychology of Bern University headed by K. Graw. It was revealed among others that psychotherapy exerts a very differentiated action and that in neurotic patients and patients with personality disorders cognitive behavioural psychotherapy, Rogers psychotherapy and psychoanalytic psychotherapy, cca 100 sessions, proves definitely effective. Close to the criterium of objectively effective psychotherapy is also shape psychotherapy and systematically oriented family therapy. In the Czech Republic research is conducted on a small scale but the work is demanding as regards methods and is of a high standard. Exact research of the psychotherapeutic process and therapeutic results contributes to the gradual shaping of a psychotherapeutic model which is internally differentiated and which integrates verified findings of various psychotherapeutic schools and trends. PMID- 7987934 TI - [New therapeutic activity in geriatric psychiatry]. AB - The author mentions and describes in detail three dynamically oriented psychiatric activities which proved useful and became thus an important component of comprehensive treatment of demented patients. Part of the activating programme for patients with advanced affections of memory, orientation and concentrating capacity is Training in orientation and reality (TOR). Relaxation training (TR) helps patients to get rid of the sensation of tension, fear and uncertainty. Cognitive training (KT) helps to restore and improve cognitive functions. By means of the mentioned activities the authors reinforce persisting abilities and skills. In the conclusion the authors present recommendations which make the reader familiar with suitable communication with and treatment of clients suffering from organic brain affections. PMID- 7987935 TI - [A practical method of whole mount TEM sample preparation and the study of nuclear matrix-intermediate filament scaffolds in K562 cells]. AB - We applied culture plates with bored holes covered with FORMVAR and coated with carbon, to replace the gold grids used in conventional whole mount TEM study. Human erythroleukemia cell line K562 cells plated on the plate surface were extracted using a modified protocol to study scaffolds of nuclear matrix (NM) and intermediate filament (IF). The NM of the K562 cells was found to be composed of interweaving filaments of different diameters, while the cytoplasmic IF were mainly distributed in a radialized pattern. Compared with other techniques of whole mount TEM sample preparations, this one is much more practical and economical, yielding clear NM-IF structures with few artifacts. Study of NM-IF scaffolds in K562 cells might provide a basis for further elucidation of the involvement of NM-IF in the denucleation of mammalian erythroblasts. PMID- 7987936 TI - [Studies on the relationship between HPV and respiratory tract tumors. I. Correlation between HPV and laryngeal carcinoma]. AB - In this paper, alpha-32P-dCTP-labeled HPV-11 and HPV-16 DNA were used as probe, and slot and Southern blot hybridization techniques were used to detect HPV-11 and HPV-16 DNA related sequences in 37 laryngeal carcinoma tissues taken from patients in Qingdao and Beijing. Using the slot blot technique, 86% (32/37) of the cases showed positive hybridization with HPV-11 probe, while 81% (30/37) showed positive results with HPV-16. Another 81% (30/37) showed positive hybridization with HPV-11 and HPV-16 simultaneously. Using Southern blot hybridization Pst digestion, the hybridization pattern corresponded to that of HPV-16 in 46; (13/28), and none corresponded to HPV-11. The results suggest that HPV-16 may induce laryngeal carcinoma. PMID- 7987937 TI - [The preliminary experiences of diagnosis and treatment for hypercalcemia crisis- clinical analysis of 23 cases]. AB - This article report a study of 23 cases of hypercalcemia crisis resulting from primary hyperparathyroidism (18 cases), carcinoma (4 cases) and vitamin D intoxication (1 case). In addition to the symptoms of primary diseases, the patients with hypercalcemia crisis often had anorexia, nausea, vomiting, polydipsia, polyuria, psychoneurotic symptoms, arrhthmia. The severity of the symptoms was proportional to the degree of hypercalcimia. Serum calcium concentration of patients in hypercalcemia crisis should be equal or higher than 3.75 mmol/L (15 mg/dl) or serum ionized calcium higher than 1.88 mmol/L. Treatment hypercalcemia crisis consisted of rapidly lowering the serum calcium level by various measures while actively treating the primary diseases. Our experience is to supply normal saline intravenously or orally to increase the extracellular fluid and to enhance excretion of the urine calcium by administrating furosemide. In this paper, serum calcium concentration of 5 patients with hypercalcemia crisis treated with salmen calcitonin was reduced in varying degrees. The above mentioned treatment would be beneficial to the alleviation of the crisis and the preparation for operative treatment. PMID- 7987939 TI - [Kaschin-Beck's disease in children's wrists: radiographic findings]. AB - Based on the analysis of hand radiographs in 208 children with Kaschin-Beck's disease, the author's chief conclusions are as follow: The more severe Kaschin Beck's is, the more opportunity the carpals have to be involved. Generally speaking, the capitatum and hamatum are frequently involved if the disease involves the carpals. PMID- 7987938 TI - [A primary clinical trial of genital warts treated with domestic highly purified podophyllotoxin]. AB - Genital warts (condyloma accunimata) are a kind of sexually transmitted disease (STD) caused by human papillomavirus (HPV). In this article, we report 75 cases of genital warts treated with highly purified podophyllotoxin. All volunteers were selected in our clinic and diagnosed according to typical skin lesions and positive 0.5% acetic acid test. Of the 74 cases 48 were male and 26 were female, with a mean age of 28.4 years (21-54). The average duration of disease was 4.4 months (2 weeks-3 years). All lesions were treated with 0.5% podophyllotoxin ethanal solution topically 2 times per day for 3 successive days. The treatment was repeated if any warts persisted, but not more than 3 therapies in total were applied. The results showed that 41/48 (85.4%) of male and 23/26 (88.5%) of female patients were cured, the overall cure rate was 86.5% and the effectiveness rate (more than 50% lesions disappeared) was 96.15%. During another 3 months of follow-up, 9 male and 4 female patients (17.6% in total) experienced relapsed warts; these were cured with another treatment. Side effects including slight local irritation and erythema or superficial erosions were common, but 3 male and 2 female patients complained of sever pain and local swelling. All side effects were tolerable. It is concluded that our domestically produced highly purified podophyllotoxin is an effective, comparatively safe drug for the treatment of genital warts. It is also very simple to apply, and can be used for self treatment. PMID- 7987940 TI - [Prostaglandin E2 levels in gingival crevicular fluid and its relation to the depth of periodontal pocket in patients with periodontitis]. AB - The prostaglandin E2(PGE2) levels in gingival crevicular fluid (GCF) of 46 normal controls and 90 patients suffering from periodontitis with periodontal pocket of different depth were measured by radioimmunoassay (RIA). The results demonstrated that the PGE2 levels in GCF of the periodontal pockets in periodontitis with different depth were higher than normal controls. The PGE2 levels increased with the depth of the periodontal pocket, particularly when the depth exceed over 6 mm. This study shows that the PGE2 levels are significantly related to the severity of bone destruction in periodontitis. PMID- 7987941 TI - [The alteration of histidase catalytic activity and the expression of the enzyme protein in rat primary hepatomas]. AB - The catalytic activity of histidase and the expression of the enzyme protein were investigated in rat hepatomas induced by diethylnitrosamine. The results indicated that the activities of histidase in the hepatomas were significantly diminished as compared with normal rat livers (P < 0.01). Western blot analysis revealed that enzyme protein levels in hepatomas were markedly reduced. It is thus inferred that some factors which control expression of histidase protein may be altered during carcinogenesis. These findings lay a foundation for studying the relationship between the regulation and expression of the histidase gene and hepato carcinogenesis. PMID- 7987942 TI - [The effect of 764-3 on platelet aggregation and the activity of enzymes in arachidonic acid metabolism]. AB - 764-3 is a purified compound extracted from Chinese herb Salvia miltiorrhizae. It was found to inhibit human and rabbit platelet aggregation induced by AA or ADP. Using AA as the substrate and pig lung microsome to provide enzymes, low doses of 764-3 (5-100 micrograms/ml) promoted the generation of 6-keto-PGF1 alpha in a dose-dependent manner. At a dose of 500 micrograms/ml, both TXB2 and 6-keto-PGF1 alpha production were inhibited. The results suggest that low dose of 764-3 may be able to bring a balance between TXB2 and 6-keto-PGF1 alpha. PMID- 7987943 TI - [Alteration of human leukocyte antigens in human parathyroid tissues after transplantation into nude mice]. AB - Human parathyroid (PTG) tissues from cadaver (C-PTG), 20-28 wk fetus (F-PTG) and PTG adenoma (A-PTG) were transplanted into the kidney subcapsular spaces of Balb/C nude mice as interim host. Dynamic changes in the amount of human leukocyte antigens (HLA) in human PTG grafts within the transplantation period were observed. The results showed that during 100 days of interim hosting, no obvious changes in the amount of tissue HLA class I antigens occurred, but the amount of tissue HLA class II antigens were significantly reduced, The changes of HLA antigens in the different types of donor human PTG tissues were compared. PMID- 7987944 TI - [Treatment of hypertensive intracerebral hematoma by CT-directed puncture aspiration and negative-pressure drainage--analysis of 120 cases]. AB - Puncture aspiration and negative-pressure drainage have been performed in 120 patients with hypertensive intracerebral hematoma. The results demonstrated that the CT-directed location method designed by us, based on Matsumoto and Hondo, s location method, is simple, practicable, very accurate and less. When intracranial CT and clinical manifestations of hematoma are comprehensively analyzed, an operative indication can be correctly selected. Depending on CT manifestations and pathological changes, the selected operative time is 48h or so. Of the 120 patients which underwent this operation, only 31 have died. The mortality rate is 25 percent. The effect of the therapy is satisfactory. PMID- 7987945 TI - [Effects of cell differentiation on the induction and inhibition of cancers]. PMID- 7987947 TI - [Molecular cytogenetic studies of soft tissue tumors]. AB - Molecular cytogenetic studies of 25 cases of soft tissue tumors, including 8 malignant fibrous histiocytomas (MFH), 13 rhabdomyosarcomas (RMS), 3 Ewing's sarcomas (ES) and 1 synovial sarcoma (SS), were performed. Chromosomal analysis showed that of 17 analyzable cases, 15 had chromosomal numerical and structural abnormalities. In RMS, ES and SS consistent chromosomal abnormalities, t(2;13) (q37;q14), t(11;22) (q24;q12) and t(X;18) (p11;q11), respectively, were found, and the remaining 2 had normal karyotypes. Southern blot analysis demonstrated that in 14 cases with matched normal (N) and tumor tissue (T) DNA (5 MFH, 6 RMS, 2 ES, 1 SS), RFLPs changes including loss of allele, partial gene deletion, rearrangement and amplication had occurred at 8 loci (D1S57, D2S44, MYL1-3, D2S3, D13S1, D13S30, ESD and D17S5, respectively). Among these loci, gene changes on D1S57 and D2S44 were found to be shared by MFH, RMS, ES and SS, and D17S5, D2S3 and ESD abnormalities were shared by MFH, ES and SS, as well as by MFH and RMS. These results suggest that a multilocus and multistep process may be involved in the carcinogenesis of MFH, RMS, ES and SS. PMID- 7987946 TI - [Effects of ligustrazine and nitroglycerine on acute hypoxic pulmonary hypertension in anesthetized dogs]. AB - The effects of ligustrazine and nitroglycerine on acute hypoxic pulmonary hypertension were observed in 10 anesthetized dogs. The results showed that ligustrazine (40 mg/kg) significantly reduced the hypoxic mean pulmonary artery pressure (PAPm) and pulmonary vascular resistance (PVR) the 10th and 15th minute after its injection into the right atrium, respectively. Its action was blocked by the continuous intravenous injection of methylene blue (1 mg/kg/min). It was suggested that the action of ligustrazine could be mediated by endothelium derived relaxing factor. It was also discovered that nitroglycerine (40 micrograms/kg) could quickly decrease PAPm and PVR, indicating that nitroglycerine can be used to treat acute pulmonary hypertension and the aggravation of chronic cor pulmonale. PMID- 7987948 TI - [Differential diagnosis of benign and malignant thyroid tumors with two dimensional and color Doppler ultrasonography]. AB - Fifty-three cases with thyroid tumors (10 carcinomas, 16 adenomas and 27 nodular goiters) confirmed by operation and pathology were investigated by two dimensional and color Doppler ultrasonography. The findings were as follows: malignant tumors usually had hypoechoes, indistinct and irregular margins, microcalcification, distal echo attenuation and arterial flow signals at the periphery as compared with benign tumors (P < 0.05). But differences in "halo" signs, degree of flow signals and interposed arterial vessels showed no statistical significance (P > 0.05). The clinical significance of high-velocity Doppler signals in the tumors and the pathologic basis of various sonographies of benign and malignant tumors are also discussed. PMID- 7987949 TI - [The physiological function of plasma apoA-I--the anti-viral effects of apoA-I and its fragments]. AB - Apolipoprotein A-I (apoA-I), the major protein of plasma high density lipoproteins, was found to inhibit herpes simplex virus type I (HSV-I) induced cell fusion at physiological concentrations (mumol/L). Plasma apoA-I from three different species was used to study the anti-viral effects by microneutralization test. Marked inhibition of virus-induced cell fusion was observed when the virus or the cells were pretreated with apoA-I, suggesting that apoA-I may have a direct effect on the virus and the cells. This function may be related to the structure of apoA-I. PMID- 7987950 TI - Geriatric nursing and the mobility of the patient. PMID- 7987951 TI - Facial cleft deformities: maternal perceptions regarding causes and interventions. AB - Maternal perceptions regarding the causes of a facial cleft deformity as well as the quality of support during medical interventions were surveyed with an open ended questionnaire. The sample consisted of 138 mothers of children up to 10 years of age attending a facial cleft deformity clinic. The responses were content analysed and thematically grouped. It was found that the subjects' views regarding the causes of facial cleft deformities changed markedly after attending counselling sessions. Ignorance about scientifically verified causal variables such as infections, medication, situational and hereditary factors decreased appreciably. The counselling sessions appeared to play an essential role in the subjects' understanding and coming to terms with their children's deformity. Their comments concerning the children's treatment in general hospitals as well as the facial cleft unit included both frustration and praise. Suggestions on enhancing support emphasised the need for accessible information, greater reassurance from medical staff at the general hospitals where delivery took place, the formation of support groups, speedy diagnosis and referral to a multiprofessional unit as well as being allowed to be with their children in hospital before and after surgical interventions. The results were discussed and tied to the available literature. PMID- 7987952 TI - Attitudes and knowledge about hysterectomy: a study of women in Mmabtho. AB - Thirty women aged 18 to 50 years (mean age = 28) completed a questionnaire measuring attitudes and knowledge about hysterectomy. The results showed that almost 60 percent of the respondents lacked knowledge about the procedure and that educational level made no significant difference to knowledge about hysterectomy. The data also indicated that many respondents were uncertain about hysterectomy. Analysis of the reasons given for their attitudes showed that many women held unfounded fears about the procedure. It is recommended that efforts be made to change the negative perception of hysterectomy. PMID- 7987953 TI - [Nursing study on the occurrence of unplanned home births in Tygerberg Hospital]. AB - A retrospective, descriptive study was conducted from March to May 1992 to investigate the incidence, factors associated with, and neonatal and maternal complications of babies born before arrival (BBA) at the Tygerberg Hospital and its peripheral clinics. This was done by means of a personal interview with 30 of the mothers within 6 hours after the birth of their babies, representing 44% of the study population during the period the study was undertaken. The incidence of BBA over the period was 5.3%. The typical patient who presented with BBA, was found to have little education, no or small income, gravida 2 and between the ages of 20 and 25 years. As much as 47% of patients did not have transport available. Only 53% of patients received specific guidance as to when to come to the hospital or clinic. The majority of these "informed" respondents, did not fully understand the information given to them. Maternal complications included vaginal and perineal lacerations, retained placenta and abruptio placentae. 47% of babies developed complications. Neonatal death, breech presentation, prematurity and umbilical cord around the neck, featured prominently. The lack of transport and inadequate or ineffective prenatal guidance and information as well as relative illiteracy were identified as the most important causative factors. The solution to the problem lies at least partially in better prenatal guidance, which includes specific reference to the symptoms of the onset of labour and the timely arranging of transport. PMID- 7987954 TI - Factors influencing the relapse of outpatients with schizophrenia in the Kentani area of Transkei. AB - A survey was carried out to establish the rate of relapse of patients with schizophrenia in one area of the Transkei. Case studies were completed on relapsed and non-relapsed patients to identify factors which play a role in relapse. Twenty percent of patients referred to this area for aftercare never appeared at clinics. Twenty-three percent of the patients were readmitted within one year. The study identified factors in the patient, the family and the community which relate to relapse. PMID- 7987955 TI - The views of primary health care practitioners regarding legal limitations influencing the practice of primary health care nurses in South Africa. AB - An exploratory descriptive study was performed within the South African context to determine the legal limitations which influence the practice of the registered primary health care nurse. Primary health care medical practitioners and nurses were interviewed to ascertain their views on these limitations. The results confirmed various limitations that need to be rectified by means of the amendment/deregulation of selected legislation. It is also recommended that a model for professional accountability, suitable for the South African health care delivery system, be developed. PMID- 7987957 TI - Women and power in nursing. AB - Power is inherent in all relationships and is subject to social and political amendment. In addition social relationships can be and are dynamic, flexible, variable and may provide unlimited possibilities for influencing the course of events in the workplace. Because of such potential, an element of competitiveness amongst leaders (and thus nurse managers) for the retention of their power base is created. Since the potential for power struggles is a realistic possibility the author contends that nurse managers need to acquaint themselves with political game playing techniques and ways of enhancing their social rank on an institution wide basis. This could be effected by concerted efforts to act in relation to others and by equipping themselves with more than basic preparation in administration and management. Nurses should use their individual and collective power, influence and authority to ensure that the nursing profession may prosper and grow. Contrary to the view that women are the weaker sex, numerically they dominate the nursing profession in South Africa. They should therefore regard the reshaping of their future role and status as a responsibility, a privilege and a challenge to the power inherent in them. PMID- 7987958 TI - An evaluation of the quality of nursing care rendered to patients with intravenous infusions in the Windhoek Hospital Complex. AB - Patients on intravenous infusions are commonly seen in the Windhoek Hospital Complex. There was concern regarding the type of nursing care these patients received which led to a survey on the quality of care rendered to these patients. The findings showed that care delivered ranged from very poor to good. Some startling information became evident in that legal aspects were often ignored and that basic things such as calculating and charting the daily intake and output, were omitted. Most of these problems can be rectified through in-service education. PMID- 7987956 TI - Prevalence and risk factors for malnutrition among children aged 5 years and less in the Lefaragatlha village of Bophuthatswana. AB - A cross-sectioned study was conducted at the Lefaragatha village of Bophuthatswana to document the prevalence and risk factors for malnutrition in children aged 0-5 years in June 1991. Fifty four households, in which there were children in the right age groups, were interviewed over three weeks. Of these children 14 (25.9%) were below the 3rd percentile of weight for age of the 1976 National Centre for Health Statistics standards; in the age group of 2 years and less, this figure was 28.6%, while in children older than 2 years the corresponding figure was 71.4%. Malnutrition was associated with a mother's consumption of alcohol and lack of resources such as water and an inappropriate staple diet. Education and income were not significant variables. PMID- 7987959 TI - Towards enhanced OSCE in Australian nurse education: a contribution from South Africa. AB - In the area of nurse education, one of the most advanced countries in the world in terms of the use of the Objective Structured Clinical Examination (OSCE) is South Africa. South African nurse educators have developed and implemented the use of OSCE as a form of assessment and evaluated its effectiveness over a considerable number of years. In contrast the use of OSCE in nurse education in Australia is in its infancy. This paper describes an in-depth case study undertaken to gather information from South African experts in pre-registration nurse education about clinical skills evaluation and, in particular, about the use of OSCE. Recommendations about the development, administration and evaluation of OSCE generated from this information provided a resource and guide that could be used in the development and refinement of OSCE in the context of pre registration nursing education in Australia. The findings of this study, along with information about the pre-registration context of nurse education in Australia to which they are intended to be applied, are presented. This provides feedback to those who participated in the study and information for nurse educators interested in reviewing their OSCE strategies. PMID- 7987960 TI - [Adaptation of the Health Belief Model for the prevention of HIV infection]. AB - The spreading of AIDS in the RSA occurs mainly through sexual transmittance, therefore people that divulge in high risk behaviour must be motivated to change their behaviour to such an extend that they won't expose themselves as well as other people to HIV infection. An AIDS tragedy in SA can only be averted by preventing HIV infection. That can only occur by changing HIV risk behaviour. As there is no antidote against AIDS, the changing of risk behaviour is the only preventative mechanism against the feared disease. The Health Belief Model is repetitively proved to have been a successful model to change behavioural patterns. The model is specifically adapted for this study. PMID- 7987961 TI - An analysis of the risk factors for coronary heart disease in patients aged 55 and younger with proven heart disease. AB - Reversible and non-reversible risk factors were studied in 207 patients with proven coronary heart disease (CHD) aged 55 years or less who had recently undergone coronary artery bypass grafting (CABG). Major reversible risk factors for CHD: cigarette smoking history, hypercholesterolaemia and hypertension and the minor risk factors obesity, sedentary lifestyle and diabetes; and in females the oral contraceptive pill; as well as the non-reversible risk factors such as a positive family history of CHD were assessed. Smoking was present in 83.1%, hypercholesterolaemia (5.2 mmol/l) in 80.2%, and a history of hypertension in 30.4% of the patients. One or more of the major reversible risk factors was present in 82.6% of the patients and only 1% had no risk factors for CHD. The presence of reversible risk factors indicate "destructive lifestyles" and operate even in the presence of known CHD. A strong case is made for a preventive programme for this group of patients. PMID- 7987962 TI - Student status in nursing: a position paper. PMID- 7987963 TI - [Parents' experience of the death of their baby with congenital disorder]. AB - The purpose of this study is to determine the experiences of the parents after the death of a congenital abnormal baby. Parents who have lost a baby go through a process of grief. This also applies to parents of a baby with congenital abnormalities. Parents whose congenital abnormal baby dies, not only grieve because of the abnormality of their baby, but also because it died. Unstructured in-depth interviews were held with six couples within a year after the death of their babies. The experiences of the six couples were afterwards compared. A literature study was undertaken in order to determine what the conclusions of other researchers field were. The result of the literature study was compared with that of the present study. Recommendations are made at the end of this study on the practical applications, education and further research that can be undertaken on this subject. PMID- 7987964 TI - Laminin localization and gelatinolytic activity of epithelial rest of Malassez grown on titanium. AB - The purpose of this study was to examine laminin localization in epithelial rests of Malassez grown on titanium and their gelatinase activity. Laminin localization was confirmed by immunocytochemistry in all epithelial cells grown on titanium. The conditioned medium from the epithelial cells grown on titanium exhibited 72kD and 92 kD-gelatinase activities by gelatin zymography. Those results suggest that laminin contributes to the epithelial cell attachment to titanium and that gelatinases may be mobilized for epithelial cell movement on titanium. PMID- 7987965 TI - pH response of human dental plaque to chewing gum supplemented with low molecular chitosan. AB - The effects of low molecular chitosan (LMCS) on pH responses of human dental plaque following exposure to fermentable carbohydrates were investigated by an ion-sensitive field-effect transistor electrode system. After the plaque pH values were minimized by direct application of 5% glucose solution or consumption of sugared caramel, the subjects started chewing the test gums containing 0 (control), 1 or 3% (w/w) LMCS for three minutes. The pH response was monitored until it recovered to over pH5.5. In the case of the glucose solution, chewing 3% LMCS gum caused significantly more rapid pH recovery toward the resting level than did the control gum. Initial pH rising rate during gum chewing was faster with either of the two LMCS gums than with the control gum. In the case of caramel, additional effects of LMCS were observed numerically as LMCS content increased. The findings indicated that LMCS had a potential to promote recovery of plaque pH after acidogenic challenge and to maintain the plaque pH around neutrality. PMID- 7987967 TI - B-cell mitogenicity and IL-1 beta production of lipopolysaccharides from various Capnocytophaga strains. AB - To evaluate the etiological roles of Capnocytophaga species in the pathogenesis of periodontal disease, we examined the immunological activities of lipopolysaccharides (LPSs) from various Capnocytophaga strains. All LPSs from various Capnocytophaga species were mitogenic for BALB/c mouse spleen cells, although the responses were lower than those to reference LPSs from Escherichia coli or Salmonella typhimurium. LPSs of C. sputigena strains had polyclonal B cell activation and adjuvant activity and were comparable to reference LPSs. All LPSs from Capnocytophaga strains activated the interleukin-1 beta production from human peripheral monocytes, although the inducing activities of Capnocytophaga LPSs were lower than those of reference LPSs. It appears that LPSs from various Capnocytophaga strains activate certain immunological responses from lymphocytes and monocytes which may be important in the development and pathogenesis of periodontal disease. PMID- 7987966 TI - Polyclonal B cell activation, endotoxin tolerance, and limulus tests of endotoxin preparations of some periodontopathogens. AB - Potencies of polyclonal B-cell activation in C3H/HeN mice of Actinobacillus actinomycetemcomitans, Fusobacterium nucleatum, and Porphyromonas gingivalis endotoxins were 0.36, 0.13 and 0.04, taking Salmonella abortusequi as 1.0. F. nucleatum and P. gingivalis endotoxins showed positive reactions in C3H/HeJ mice. Most activities in C3H/HeN other than that of F. nucleatum were suppressed by polymyxin B. In C3H/HeJ mice, similar inhibitions were only 60% for P. gingivalis and hardly observed with F. nucleatum. The resistances to polymyxin B could be due to protein in the endotoxins. A promoting effect of T cells added to B cells was observed only in the activity of F. nucleatum endotoxin in C3H/HeJ mice; there was no influence in other groups. Test endotoxins had nearly the same ability to produce colony stimulating factor as did references and could not produce the factor in tolerant mice. The clinical significance of tolerance is discussed. Regression lines of endotoxin doses and limulus activities of test endotoxins and Salmonella were parallel, either in specific or non-specific tests. The lines of two test groups were also parallel; values obtained by two tests were very close. These data indicate that the test endotoxins did not contain (1-3)-beta-D-glucan and elicited qualitatively similar limulus reactions to that of the reference, despite their different chemical natures. In conclusion, these test preparations had an endotoxicity similar to that of the reference and contribute to produce periodontitis through polyclonal B cell activation. PMID- 7987968 TI - An orthodontic study of temporomandibular joint disorders. Part 2: Clinical research in orthodontic patients. AB - The purpose of this survey was to investigate the symptoms of temporomandibular joint disorders (TMD) in orthodontic patients and to define the relationships between symptoms and malocclusion and/or orthodontic treatment. The subjects were 532 patients, 6 to 38 year old Japanese, in the orthodontic department of Tokyo Dental College Hospital. They were examined for past or recent TMJ sounds, pain in the TMJ area, and abnormal jaw movements. The prevalence of TMJ symptoms was 33.8%. Sex differences were not statistically significant. The prevalence of TMD symptoms increased with age. TMD symptoms in young orthodontic patients (6-18 years old) were more common than in untreated subjects. Posterior crossbite and open bite patients had a high prevalence of symptoms. PMID- 7987969 TI - A study of the subgingival microflora of HIV-seropositive and CD4 cell depleted children with hemophilia. AB - The cultivable subgingival bacterial flora from three HIV-seropositive and CD4 cell depleted children with hemophilia were examined in this study. The numbers of CD4 cells of the subjected children ranged from 4.9 to 16.3 per mm3 blood. Streptococcus species, including, beta-hemolytic streptococcus identified as Streptococcus mutans and Streptococcus sanguis, were predominant in the subgingival plaque samples. Actinomyces species were also frequently found. Gram negative rods other than Capnocytophaga species were not common in these samples. It is possible that the subgingival microbial flora are influenced by the CD4 cell decrease with HIV infection. PMID- 7987970 TI - Merkel cell-neurite complexes in touch domes of hamster cheek pouch. AB - Morphological study has been done in touch domes of hamster cheek pouch as a preparation for further electrophysiological study. The touch domes were examined by light and electron microscopy. There were one or two primary ridges (epithelial ridges) in the center of the touch dome, and each dome was supplied by one to three nerve fibres. Tactile cells (Merkel cells) were localized within primary ridges of touch domes and Merkel cell-neurite complexes were observed in every one. Since Merkel cell-neurite complexes are slow adapting mechanoreceptors, these results suggest that they might be involved in touch sensation. PMID- 7987971 TI - Inhibitory effects of exogenously applied met-enkephalin on submandibular ganglion cells. AB - In this study, effects of exogenously applied Met-enkephalin on hamster submandibular ganglion cells were investigated using an intracellular recording technique. Met-enkephalin (10 microM) was applied to cells by pressure ejection (2 kg/cm2, 50 msec) from a micropipette. More than 30% of the cells caused a hyperpolarization (amplitude: about 3 mV) accompanied by an increase in potassium conductance. After 30-40 ejections, the Ca2+ spike was shortened by 18.1%, and the nicotinic transmission was depressed. The inhibitory effect on presynaptic terminals was blocked by naloxone (10 microM). PMID- 7987973 TI - Photodynamic enhancement of doxorubicin cytotoxicity. AB - Argon ion laser irradiation at 514.1 nm and 488 nm dramatically increased doxorubicin cytotoxicity in an L929 cell clonogenic survival assay. The cytotoxicity was dependent on both the drug concentration and the total light energy delivered such that at 5 micrograms doxorubicin/ml and 800 J/cm2, cytotoxicity was enhanced by a factor of > 10(4) relative to that achieved with drug alone. Irradiation times in excess of 2 min and power densities in excess of 100 J/cm2 were required to produce the effect. Beyond this 2-min limit, cytotoxicity was not related to the duration of exposure if the total energy delivered was held constant. The ability of catalase and superoxide dismutase to abolish completely the increase in cytotoxicity produced by laser irradiation suggests that the cytotoxic mechanism may depend on the generation of active oxygen species by the photodynamically excited drug. PMID- 7987972 TI - Cisplatin-induced renal toxicity and toxicity-modulating strategies: a review. PMID- 7987974 TI - Human metabolism of the experimental cancer therapeutic agent d-limonene. AB - d-Limonene has efficacy in preclinical models of breast cancer, causing > 80% of carcinomas to regress with little host toxicity. We performed a pilot study on healthy human volunteers to identify plasma metabolites of limonene and to assess the toxicity of supradietary quantities of d-limonene. Seven subjects ingested 100 mg/kg limonene in a custard. Blood was drawn at 0 and 24 h for chemistry panel analysis and at 0, 4, and 24 h for limonene-metabolite analysis. On-line capillary gas chromatography/mass spectrometry (GC/MS) analysis indicated that at least five compounds were present at 4 h that were not present at time zero. Two major peaks were identified as the rat limonene metabolites dihydroperillic acid and perillic acid, and two minor peaks were found to be the respective methyl esters of these acids. A third major peak was identified as limonene-1,2-diol. Limonene was a minor component. At a dose of 100 mg/kg, limonene caused no gradable toxicity. Limonene is metabolized by humans and rats in a similar manner. These observations and the high therapeutic ratio of limonene in the chemotherapy of rodent cancers suggest that limonene may be an efficacious chemotherapeutic agent for human malignancies. PMID- 7987975 TI - Kinetics of tissue disposition of cis-ammine/cyclohexylamine-dichloroplatinum(II) and cisplatin in mice bearing FSaIIC tumors. AB - The clinical potential of mixed amine platinum(IV) complexes has been identified, and interest in this new class of antitumor agents has been heightened by demonstration of their activity in cisplatin-resistant neoplasms. These tetravalent platinum agents are expected to undergo a reductive reaction to form the corresponding platinum(II) drug prior to eliciting biological activity. cis Ammine/cyclohexylamine-dichloroplatinum(II) is one such product that we evaluated with cisplatin in vivo, and we found the two complexes given i.v. or i.p. to have comparable activities against a solid murine fibrosarcoma. Following i.v. administration of the two compounds at equitoxic dose levels (20 mg/kg) to tumor bearing mice, platinum levels in the plasma were consistently higher for cisplatin. Tissue platinum levels, in contrast, were comparable between the agents or higher for the mixed amine analog at the earliest (3-h) time point. The temporal profiles determined for the concentrations over 48 h were tissue- and/or drug-specific and could be described by terminal-phase constants or half-lives of platinum in most tissues. In the plasma, kidney, lung, and jejunum, platinum levels arising from both compounds decayed with half-lives of 24-92 h. The terminal-phase constants of platinum determined in the heart for the two complexes were not significantly different from zero, indicative of levels remaining steady, whereas the constants were negative in the spleen, indicative of an increase in tissue drug concentration. In the tumor, liver, and testes, positive values for the decay-phase constants corresponding to half-lives of 47, 256, and 79 h, respectively, were seen with the mixed amine complex; this pattern contrasted with that found for cisplatin, for which the terminal-phase constant was either zero or negative. In vitro binding studies demonstrated the mixed amine complex to be more reactive. Thus, the presence of one ammine and one cyclohexylamine carrier ligand in the mixed amine complex, as opposed to the diammine ligands in cisplatin, leads to an increase in drug distribution and an alteration in the kinetics of tissue binding and removal of platinum. PMID- 7987976 TI - The pharmacokinetics of high-dose epirubicin and of the cardioprotector ADR-529 given together with cyclophosphamide, 5-fluorouracil, and tamoxifen in metastatic breast-cancer patients. AB - A high-pressure liquid chromatographic method for determination of the bisdioxopiperazine derivative ADR-529 (ICRF-187), a compound proven effective in protection against anthracycline-induced cardiotoxicity, has been developed. The limit of quantitation was 5 ng/ml using a narrow-bore 5-microns silica column and UV detection. The method was used for determination of pharmacokinetic profiles of ADR-529 after a 3-weekly i.v. administration of different doses of ADR-529 (600-1000 mg/m2) together with different doses of epirubicin (E, 60-100 mg/m2), fixed-dose cyclophosphamide (C, 600 mg/m2), fixed-dose 5-fluorouracil (F, 600 mg/m2), and daily administration of tamoxifen (T, 30 mg; CEF-T) in the treatment of patients with metastatic breast cancer. Pharmacokinetic parameters for epirubicin were also determined. The aim of the study was to determine (1) whether the pharmacokinetics of ADR-529 as part of a combination with CEF-T changes with increasing doses of ADR-529 and increasing doses of epirubicin and (2) whether the pharmacokinetics of epirubicin in the same combinations is altered with the administration of increasing doses of ADR-529. A total of 82 patients were included. A crossover study including 16 of the patients showed no significant difference in epirubicin pharmacokinetic parameters when epirubicin was given with or without concomitant administration of ADR-529. Apart from minor changes in the distributional half-lives, the pharmacokinetic parameters of epirubicin were not altered with increasing doses of ADR-529, nor were the pharmacokinetic parameters of ADR-529 itself. Escalating doses of epirubicin did not significantly alter the pharmacokinetic parameters of ADR-529 with the exception of a 30% increase in the terminal half-life and a decrease in total body clearance when the epirubicin dose was raised from 60 to 100 mg/m2. We conclude that concomitant administration of ADR-529 does not alter the distribution and elimination of epirubicin in doses suitable for preventing the anthracycline-induced cardiotoxicity. PMID- 7987977 TI - Modulation of anthracycline accumulation and metabolism in rat hepatocytes in culture by three revertants of multidrug resistance. AB - The aim of this study was to compare the action of three multidrug resistance (MDR) modulators, cyclosporine A, S 9788, and verapamil, on the efflux of two anthracyclines, doxorubicin and daunorubicin, and of daunorubicinol, the C-13 alcohol metabolite of daunorubicin. Rat-hepatocyte primary cultures have been used as a model of P-glycoprotein (Pgp) expression. This model allows the study of MDR at different levels of Pgp expression, which increases in parallel with the time in culture; furthermore, the hepatocytes are capable of metabolizing drugs, which enables the determination of the role of Pgp on metabolite efflux. All modulators tested were incubated for 6 h at concentrations of 1, 5, and 15 microM with doxorubicin (0.5 microM) and at 1 and 15 microM with daunorubicin (0.5 microM) on hepatocytes grown for 4 and 48 h in culture. Daunorubicinol (0.5 microM) was tested with modulators at 48 h of culture. In fresh hepatocytes, the three MDR modulators did not induce an increase in the intracellular retention of anthracycline as compared with controls (no MDR modulator). At 48 h of culture, the three test drugs increased doxorubicin intracellular accumulation. In contrast, daunorubicin retention was not modified, but that of its metabolites was increased. Within the concentration range tested, cyclosporine was the most potent modulator without dose-dependent activity. The activity rank order was cyclosporine > S 9788 > verapamil. Cyclosporine and S 9788 were as active in coincubation as in preincubation with anthracyclines. Verapamil had no action when incubated before the addition of anthracyclines. Cyclosporine and S 9788 had an effect on the intracellular retention of daunorubicinol used alone whereas verapamil did not. The action of cyclosporine and S 9788 on the retention of daunorubicinol proves that at least a part of the efflux of C-13 alcohol metabolites of anthracyclines is mediated by Pgp. This study shows that S 9788, cyclosporine, and verapamil are MDR modulators in hepatocytes with high-level Pgp expression. This study also demonstrates that hepatocytes are a potent tool for the study of the action of new MDR modulators on cytostatic drugs as well as on their metabolites. PMID- 7987978 TI - Cyclophosphamide, cisplatin, and carmustine: pharmacokinetics of carmustine following multiple alkylating-agent interactions. AB - Cyclophosphamide, cisplatin, and carmustine (CPA/cDDP/BCNU) constitute a combination alkylating-agent regimen commonly used with autologous marrow support. Its therapeutic effectiveness is accompanied by sporadic life threatening and fatal toxicities, the most common of which is acute lung injury. We have previously shown that variation in the BCNU AUC can be correlated to the risk of pulmonary injury in patients receiving CPA/cDDP/BCNU. In an attempt to understand further the role of interpatient variation in drug pharmacokinetics (PK) with respect to pharmacodynamic outcomes, we evaluated the effect of pretreatment with CPA, cDDP, or both on BCNU PK in male Sprague-Dawley rats. The drug-administration pattern was designed to mimic that of the CPA/cDDP/BCNU regimen in patients. Each pretreatment increased both the absolute value of and the variation in BCNU AUC relative to the control values. These findings are consistent with an important rate-limiting elimination pathway for BCNU in rats and may explain the wide interpatient variability of BCNU AUC and the sporadic pulmonary toxicity seen in patients receiving CPA/cDDP/BCNU. PMID- 7987979 TI - Plasma 5-fluorouracil and alpha-fluoro-beta-alanin accumulation in lung cancer patients treated with continuous infusion of cisplatin and 5-fluorouracil. AB - This study was undertaken to investigate the day-to-day pharmacokinetic variability of 5-fluorouracil (5FU) given as a continuous i.v. infusion concomitantly with cisplatin. Ten lung cancer patients were investigated during the first course of chemotherapy. All patients had advanced, previously untreated, inoperable non-small-cell lung cancer. They received continuous infusions of cisplatin given at 100 mg/m2 over 5 days and of 5FU given at 1 g/m2 daily from day 2 to day 5. Both drugs were infused i.v. for 24 h/day at a constant rate with a volumetric pump. Blood samples were drawn from day 2 to day 5, every 4 h from 8 a.m. to 8 p.m. and every 2 h during the night (8 p.m. to 8 a.m.). Plasma 5FU and FBAL concentrations were determined simultaneously by gas chromatography-mass spectrometry. Plasma 5FU concentrations varied widely over the 4-day treatment course for each patient. Despite continuous constant-rate 5FU administration, plasma 5FU concentrations were significantly lower between 8 a.m. and 8 p.m. than during the night. Mean plasma concentrations of 5FU and FBAL increased significantly from the 1st day (0.42 and 1.19 micrograms/ml for 5FU and FBAL, respectively) to the 4th day of 5FU infusion (0.67 and 1.78 micrograms/ml for 5FU and FBAL, respectively). Further study is warranted to elucidate the mechanisms of the observed increase in plasma 5FU concentrations as well as its relationship with cisplatin coadministration and to assess the clinical relevance of this plasma 5FU accumulation. PMID- 7987980 TI - Cellular pharmacology of D-3-azido-3-deoxy-myo-inositol, an inhibitor of phosphatidylinositol signaling having antiproliferative activity. AB - D-3-Azido-3-deoxy-myo-inositol (3AMI) is an inhibitor of the growth of v-sis transformed NIH 3T3 cells but not of wild-type NIH 3T3 cells, whose effects may be mediated through the phosphatidylinositol-3'-kinase pathway. We studied some properties of the cellular pharmacology of 3AMI using high-specific-activity [3H] 3AMI. The uptake of [3H]-3AMI by wild-type NIH 3T3 and v-sis NIH 3T3 cells was similar. [3H]-3AMI was a substrate for phosphatidylinositol synthetase, with the maximal velocity (Vmax) being 1.0 nmol min-1 mg-1 and the Michaelis constant (Km) being 23 mM. Corresponding values obtained for [3H]-myo-inositol as a substrate were 5.5 nmol min-1 mg-1 and 3.2 mM. [3H]-3AMI was incorporated into the cellular inositol lipids of v-sis NIH 3T3 cells to a similar extent as that observed for [3H]-myo-inositol but was not incorporated into the inositol lipids of wild-type NIH 3T3 cells. The [3H]-3AMI incorporated by the v-sis NIH 3T3 cells was present in the phosphatidylinositol and phosphatidylinositol phosphate fractions but not in bisphosphorylated phosphatidylinositol. myo-Inositol antagonized the growth inhibitory effects of 3AMI. The v-sis NIH 3T3 cells were found to be more sensitive than the wild-type NIH 3T3 cells to growth inhibition (without 3AMI) caused by the removal of myo-inositol from the medium. The results of the study suggest that 3AMI is an antimetabolite of myo-inositol. The relative sensitivity of v-sis NIH 3T3 and some other cells to 3AMI may be a reflection of increased myo-inositol requirements for the growth of these cells as compared with wild type NIH 3T3 cells. PMID- 7987981 TI - Treatment of disease-negative but mucin-like carcinoma-associated antigen positive breast cancer patients with tamoxifen: preliminary results of a prospective controlled randomized trial. AB - Increasing levels of tumor markers such as carcinoembryonic antigen, mucin-like carcinoma-associated antigen (MCA), CA 15.3, and monoclonal antibody H23 in breast cancer patients following the treatment of the primary disease and adjuvant radiation and chemotherapy reflect subclinical development of metastatic disease. Overt metastatic disease is usually incurable and prolongation of life at this stage is impossible, and the treatment is only palliative. The efficacy of tamoxifen, a least-toxic agent, in the treatment of early and minimal metastatic disease detected only by increasing serum levels of MCA was studied prospectively in a randomized study. Our preliminary, albeit encouraging, results showed that the rate of relapse within a median follow-up period of 11 months was 24.1% in the control arm as compared with 0% in the tamoxifen arm (Fisher's exact test, P = 0.012). None of the patients with a relapse had positive progesterone receptors (PR). We may carefully conclude that early treatment may be warranted in young patients with negative PR and continuously increasing serum levels of the marker. PMID- 7987982 TI - A new procedure for the preparation of liposomal doxorubicin: biological activity in multidrug-resistant tumor cells. AB - We describe a new procedure for the preparation of liposomal doxorubicin. Doxorubicin can be efficiently complexed to preformed or lyophilized cardiolipin containing liposomes. Complex formation was performed by vigorous vortexing. As much as 96.8% of the initial drug quantity may be bound to those liposomes under optimal incubation conditions (4 h at 37 degrees C). The binding study showed the presence of two levels of specific binding (dissociation constants, 28 +/- 8 microM and 1.0 +/- 0.3 mM). The drug is firmly integrated in the liposome membrane lipid bilayer rather than binding at the surface. Cytotoxicity studies using tumor cells revealed efficient drug delivery using liposome-complexed doxorubicin. This new liposomal doxorubicin preparation reverses multidrug resistance in MCF-7/ADR and CH LZ cells at levels equivalent to that obtained with a previously described liposome-encapsulated doxorubicin preparation, showing that the drug is integrated as well in the liposome carrier and is transported as well into cells. Increased concentration of liposomes at the subcytotoxic level in liposome-complexed doxorubicin enhances drug cytotoxicity in multidrug-resistant CH LZ cells as compared with liposome-encapsulated drug. This new preparation for liposomal doxorubicin may be carried out immediately prior to clinical administration, offering advantages in terms of cost and stability. PMID- 7987983 TI - Disposition in mice of 7-hydroxystaurosporine, a protein kinase inhibitor with antitumor activity. AB - UCN-01, a hydroxylated derivative of staurosporine, was selected for study because of its promising antitumor activity. For mice dosed intravenously, subcutaneously, or by oral gavage with this compound, the maximum tolerated doses (MTD) were 20, 10, and > 100 mg/kg, respectively. UCN-01 was stable in mouse and dog plasma, but in human plasma it was converted to a metabolite in a process not inhibited by standard protease and esterase inhibitors. Following an intravenous dose of 10 mg/kg UCN-01, the half-lives for the initial (t1/2 alpha) and terminal (t1/2 beta) exponential phases of elimination were 10 and 85 min, respectively; the area under the plasma concentration-time curve (AUC value) was 117 micrograms min ml-1. In mice dosed by oral gavage with 10 mg/kg, the calculated value for the half-life of the elimination phase was 150 min. The AUC value was 15 micrograms min ml-1, giving a value for bioavailability of 13%. After subcutaneous dosing with 10 mg/kg, the calculated values for half-lives for the distribution and elimination phases were 23 and 130 min, respectively; the AUC value was 113 micrograms min ml-1. Since this value is equivalent to that obtained for intravenous dosing, administration of UCN-01 by the subcutaneous route may be an alternative to intravenous dosing in preclinical and clinical trials. PMID- 7987984 TI - Protein binding of brequinar in the plasma of healthy donors and cancer patients and analysis of the relationship between protein binding and pharmacokinetics in cancer patients. AB - The protein binding of weakly acidic and basic drugs has been shown to be altered in cancer patients. Brequinar is a weakly acidic, low-clearance, and highly protein-bound (> 98% bound) antitumor agent. The pharmacokinetic parameters of brequinar are subject to large interpatient variability. This large interpatient variability may be related to brequinar's plasma protein-binding capacity (assuming no change in the intrinsic clearance of the unbound drug). The objectives of this study, therefore, were (a) to characterize brequinar's protein binding in the plasma of healthy donors and cancer patients and (b) to examine the relationships between brequinar's plasma protein binding and its pharmacokinetics in patients. Brequinar protein binding was determined in human serum albumin (HSA) solution, drug-free donor plasma, and brequinar-free, predose plasma samples obtained from a phase I cancer trial. Pharmacokinetic results from this study were used to examine relationships between plasma protein binding and drug disposition. In HSA solution and healthy donor plasma, brequinar's protein binding as determined using spiked samples was concentration-dependent. The unbound brequinar fraction increased by a factor of 3 (from 0.3% to 0.9% free) in 4% HSA solution and by a factor of 4 (from 0.4% to 1.6% free) in donor plasma as the brequinar concentrations increased from 0.1 to 2.3 mM in the HSA solution and from 0.076 to 1.5 mM in the donor plasma. Analysis of brequinar binding characteristics using the binding ratio and Rosenthal binding plots showed that albumin was the primary protein for brequinar binding in human plasma. The addition of various concentrations of alpha 1-acid glycoprotein to 4% HSA solution did not affect the protein binding of brequinar to HSA. The protein binding determined in the plasma of cancer patients was not quantitatively different, except for variability, from that observed in the plasma of healthy donors. Examination of relationships between the unbound brequinar fraction and pharmacokinetics suggested that plasma protein binding was not a major determinant of brequinar disposition in cancer patients. PMID- 7987986 TI - Effects of neocarzinostatin upon the development of tumors from murine neuroblastoma cells. AB - The use of differentiation-inducing agents has been proposed for the purging of bone marrow and for the treatment of minimal residual disease prior to autologous bone marrow transplantation in patients with metastatic neuroblastoma. The present studies examine the effects of the enediyne differentiation inducer neocarzinostatin (NCS) on tumor development from subcutaneous implants of murine (Neuro-2A) neuroblastoma cells. Prior in vitro treatment with NCS results in a concentration- and drug exposure time-dependent decrease in the incidence of tumors from subcutaneously implanted cells. In vivo treatment results in a dose dependent decrease in the rate of tumor growth. These results imply that enediynes such as NCS may be useful in ex vivo purging regimens and in in vivo treatment of microscopic residual disease in patients with neuroblastoma. PMID- 7987985 TI - Biochemical effects of folate-based inhibitors of thymidylate synthase in MGH-U1 cells. AB - The TS-inhibitory effects induced by a 24-h exposure to the folate-based TS inhibitors CB3717, C2-desamino analogs of CB3717 including D1694, and BW1843U89 were quantitated using the MGH-U1 human bladder carcinoma. The effects of D1694 on the time course of TS inhibition and on intracellular deoxyuridine monophosphate (dUMP) accumulation and deoxyuridine (dUrd) production were evaluated. D1694 and BW1843U89 were the most active TS inhibitors with IC50 values of 2.4 and 0.5 nM, respectively. The C2-desamino C2-methyl dideazafolates were 27-292 times more potent than the parent CB3717 as TS inhibitors. A methyl group at the C2 position of CB3717 had the most dramatic effect, whereas a thiazole substitution for a benzyl added a small benefit and N10 substitution had a limited impact on TS-inhibitory potency and clonogenic survival. There was a significant correlation between the IC50 values for TS inhibition and those for cytotoxic potency obtained for these drugs. LV and thymidine protected cells from these folate-based TS inhibitors. Intracellular dUMP levels following 24 h D1694 (IC50) exposure increased 7-fold. Levels of dUrd effluxing into the media increased up to 4.5 microM following a 24-h exposure to D1694 (IC90). We conclude that (a) C2-desamino C2-methyl dideazafolates are potent TS inhibitors, (b) TS inhibition requires prolonged exposure with these folate TS inhibitors, (c) survival is correlated with inhibition of TS for the folate-based TS inhibitors and (d) the biochemical consequences of TS inhibition include increased dUMP and dUrd levels. PMID- 7987987 TI - Biodistribution of O6-benzylguanine and its effectiveness against human brain tumor xenografts when given in polyethylene glycol or cremophor-EL. AB - O6-Benzylguanine effectively inactivates the DNA-repair protein O6-alkylguanine DNA alkyltransferase in tumor cells and has been shown to increase the cytotoxicity of chloroethylnitrosoureas. This study was undertaken to ascertain the optimal vehicle for further toxicological evaluation and eventual clinical trials of O6-benzylguanine. The solubility, metabolism, bioavailability and effectiveness of O6-benzylguanine as an adjuvant therapy with BCNU were compared using two vehicles, cremophor-EL and PEG 400. Nude mice bearing s.c. D456 MG glioblastoma xenografts were injected i.p. with 10-30 mg/kg O6-benzylguanine dissolved in either 40% PEG 400/saline or 10% cremophor-EL/saline. The number of tumor regressions noted after treatment with 10 mg/kg O6-benzylguanine followed by 12.7 mg/kg BCNU were 8/9 for the drug dissolved in PEG and 1/10 for the drug given in cremophor-EL. Using the same treatment regimen but increasing the dose of O6-benzylguanine to 30 mg/kg led to a growth delay of 45.2 and 11.5 days for the drug dissolved in PEG 400 and cremophor-EL, respectively, although the number of regressions observed were the same for both treatments. 8-[3H]-O6 Benzylguanine was more rapidly distributed to the tumor when it was delivered in PEG vehicle than when it was given in cremophor-EL. In contrast, there was a 3 fold greater amount of O6-benzylguanine in the small intestine of mice at 1 h after i.p. injection of the drug in cremophor-EL as compared with PEG 400. The rate and extent of metabolism in the liver was the same, whether the parent drug was given in PEG 400 or in cremophor-EL. These studies demonstrate that O6 benzylguanine is a more effective enhancer of the antitumor activity of BCNU when it is given in PEG 400 than when it is delivered in cremophor-EL, which may be due to a more rapid distribution of the drug to the tumor. PMID- 7987988 TI - Busulfan therapy of central nervous system xenografts in athymic mice. AB - We evaluated the antitumor activity of busulfan against a panel of tumor cell lines and xenografts in athymic nude mice derived from childhood high-grade glioma, adult high-grade glioma, ependymoma, and medulloblastoma. Busulfan displayed similar activity against a panel of four medulloblastoma cell lines (D283 Med, Daoy, D341 Med, and D425 Med) and four corresponding sublines with laboratory-generated or clinically acquired resistance to 4 hydroperoxycyclophosphamide [D283 Med (4-HCR), Daoy (4-HCR), D341 Med (4-HCR), and D458 Med] and cross-resistance to melphalan. This is consistent with a nearly total lack of cross-resistance of busulfan to 4-hydroperoxycyclophosphamide. Busulfan was active in the therapy of all but one of the subcutaneous xenografts tested, with growth delays ranging from 14.3 days in D612 EP to 58.4 days in D528 EP. Busulfan produced statistically significant increases in the median survival of mice bearing intracranial D456 MG (66%-90%), D612 EP (18%-33%), and D528 EP (89%) xenografts. These studies suggest that busulfan may be active against medulloblastomas, high-grade gliomas, and ependymomas as well as against cyclophosphamide-resistant neoplasms. PMID- 7987989 TI - Depletion of total cysteine, glutathione, and homocysteine in plasma by ifosfamide/mesna therapy. AB - The sulfhydryl status of cells, particularly the intracellular concentration of glutathione, is a critical determinant of the response of tumor and normal cells to cytostatic drugs. Recent data indicate that the administration of mercaptoethane sulfonate (mesna), which is often combined with ifosfamide, markedly decreases the circulating concentration of total cysteine and could thereby influence the response of the organism to the cytotoxic effects of chemotherapy. The aim of the present study was to assess the effects of the combination of ifosfamide/mesna on sulfhydryl and disulfide homeostasis in tumor patients. Ifosfamide was infused into 14 patients with advanced sarcoma for 5 days at a dose of 2.4-3.2 g/m2 per day together with mesna. The plasma concentrations of total mesna, cysteine, glutathione, and homocysteine were measured before and on days 1 and 6 of the first course of ifosfamide/mesna therapy and prior to the next course of chemotherapy, and the urinary excretion of cysteine and mesna was monitored daily using a high-performance liquid chromatography (HPLC) method. Ifosfamide/mesna resulted in a marked depletion of circulating total cysteine, i.e., cysteine, cystine, and cysteine mixed disulfides [from 245 +/- 36 to 50 +/- 14 nmol/ml (mean +/- 95% CI) on day 6], total glutathione (from 6.9 +/- 1.1 to 2.5 +/- 1.1 nmol/ml), and total homocysteine (from 12.3 +/- 2.1 to 1.4 +/- 1.1 nmol/ml). The values returned to baseline levels prior to the next course of chemotherapy. The urinary excretion of cysteine increased significantly from 0.28 to 1.82 mmol/day on the 1st day, whereupon it returned toward baseline. An average of 62% +/- 6% of the delivered dose of mesna was recovered in urine. The combination of ifosfamide/mesna results in depletion of circulating total cysteine, glutathione, and homocysteine. This marked derangement of sulfhydryl and disulfide homeostasis could modulate the efficacy and toxicity of ifosfamide/mesna therapy. PMID- 7987990 TI - Selective potentiation of platinum drug cytotoxicity in cisplatin-sensitive and resistant human ovarian carcinoma cell lines by amphotericin B. AB - Resistance to the clinically used platinum-based drugs cisplatin and carboplatin represents a major limitation to their clinical effectiveness. Using cisplatin sensitive and -resistant human ovarian carcinoma cell lines previously characterized in terms of their major underlying mechanisms of resistance, we attempted to potentiate the cytotoxic effects of cisplatin and carboplatin using the clinically used antifungal agent amphotericin B (AmB). Using non-toxic concentrations of AmB (up to 15 micrograms/ml) and continuous exposure to cisplatin, a concentration-dependent selective potentiation (maximum of 3.2-fold) of cisplatin cytotoxicity was observed in two cisplatin-resistant cell lines (41McisR6, acquired resistant, and HX/62, intrinsically resistant). In both these cisplatin-resistant cell lines, previous studies have shown resistance to be due primarily to reduced platinum uptake. Notably, no significant potentiation was observed in the parent 41M cell line, in the intrinsically resistant SKOV-3 cell line (where reduced drug accumulation plays only a partial role in determining resistance) or in a pair of cell lines (CH1 and its acquired-resistant variant CH1cisR6) were reduced drug uptake does not play any role in determining resistance. The potentiating effect of AmB was lower with carboplatin and not significant in all cell lines. Platinum uptake following a 2-h exposure of cells to cisplatin was enhanced 3.5-fold in 41McisR6 cells (producing platinum levels similar to those obtained in the parental line) and 1.7-fold in 41M cells by the concomitant exposure to AmB. These data indicate that the potentiation of cisplatin (and carboplatin) cytotoxicity by AmB is not due to a generalized membrane disruption, as effects were observed only in resistant lines where reduced drug transport was apparent. Moreover, AmB did not increase the cytotoxicity of JM216 [bis-acetatoammine(cyclohexylamine)dichloroplatinum (II)], a recently developed, more lipophilic orally active platinum drug, in the 41M/41McisR6 lines. JM216 has previously been shown to circumvent acquired cisplatin resistance due to decreased drug uptake. In vivo, however, using the HX/62 xenograft. AmB (at its maximum tolerated dose of 20 mg/kg; q7d x 4 schedule) did not enhance the antitumour effect of carboplatin (at its maximum tolerated dose of 80 mg/kg; q7d x 4 schedule. PMID- 7987991 TI - The pharmacokinetics of reduced folates after intraperitoneal and intravenous administration of racemic [6S,R]-folinic acid. AB - We investigated the pharmacokinetics of tetrahydrofolates following the administration of [6S,R]-folinic acid and 5-flurouracil delivered i.v., i.p., and by a combination of both routes in patients with colon cancer. The concentrations of the biologically active tetrahydrofolates ([6S]-folinic acid and 5 methyltetrahydrofolate) and the relatively inert diastereomer [6R]-folinic acid were monitored using a selective on-line coupled achiral-chiral high-performance liquid chromatographic method. In plasma, a target concentration of 5 microM active tetrahydrofolates, which is considered necessary for an optimal synergistic effect, could be achieved after i.v. or combined i.v. and i.p. administration but was not reached in a patient receiving i.p. [6S,R]-folinic acid alone. In three patients receiving i.p. [6S,R]-folinic acid a high level of [6S]-folinic acid was observed in ascites, suggesting that the peritoneal cavity may act as a storage site for tetrahydrofolates after i.p. administration. In these patients, only a trace level of the active metabolite 5 methyltetrahydrofolate was detected in ascites, which may indicate that tetrahydrofolate derivatives penetrate only minimally, if at all, into the peritoneal cavity from the central compartment. These data would indicate that a combination of i.p. and i.v. administration may, from the pharmacological point of view, indeed contribute to an improved treatment of minimal residual disease persisting in the peritoneal cavity. PMID- 7987992 TI - Reduced tamoxifen accumulation is not associated with stimulated growth in tamoxifen resistance. AB - To study tamoxifen resistance-stimulated growth, 30 female ovariectomized nude mice were implanted with tamoxifen-resistant tumors and treated with 10-1000 micrograms/day of tamoxifen citrate subcutaneously. Tamoxifen stimulated MCF-7 tumor growth in a dose-dependent manner, with tumoral tamoxifen concentrations increasing proportionally to the dose (1-13 nmol/g), as measured by high performance liquid chromatography (HPLC). Flow-cytometric analysis revealed that tamoxifen-resistant tumors had a different DNA content as compared with wild-type MCF-7 cells. In contrast to earlier results, these data suggest that tamoxifen resistance-stimulated growth is associated with increasing rather than decreasing tumoral tamoxifen concentrations. Furthermore, the observed ploidy changes in the tamoxifen-resistant tumors imply that a genetic basis may exist for the development of tamoxifen resistance. PMID- 7987993 TI - Interaction between endotoxin and the antitumour agent 5,6-dimethylxanthenone-4 acetic acid in the induction of tumour necrosis factor and haemorrhagic necrosis of colon 38 tumours. AB - The investigational antitumour agent 5,6-dimethyl-xanthenone-4-acetic acid (5,6 MeXAA) induced dose-dependent haemorrhagic necrosis of colon 38 tumours to a similar extent to that induced using bacterial lipopolysaccharide (LPS). TNF alpha activity in serum and mRNA for TNF-alpha in splenocytes were induced over a broad range of LPS doses, whereas with 5,6-MeXAA, induction occurred only at concentrations approaching the maximum tolerated dose. At concentrations that provided similar degrees of haemorrhagic necrosis, the levels of serum TNF-alpha induced using 5,6-MeXAA were 100-fold lower than those obtained with LPS, indicating that haemorrhagic necrosis was not directly correlated with TNF-alpha levels. There was also no correlation between the degree of tumour necrosis and the duration of growth delay. Treatment with LPS did not induce a significant delay in growth, despite extensive tumour haemorrhagic necrosis, whereas with 5,6 MeXAA, treatments that improved the cure rate did not necessarily give longer growth delays. Therapy using a combination of sub-optimal doses of both compounds was synergistic for the induction of serum TNF-alpha and message for TNF-alpha but was not synergistic for antitumour efficacy. Thus, no correlation is evident between cure rates, duration of growth delay, haemorrhagic necrosis and TNF-alpha induction by 5,6-MeXAA or LPS. PMID- 7987994 TI - Phase I study of 5-day continuous infusion fluorodeoxyuridine and high-dose folinic acid with oral hydroxyurea. AB - Fluorodeoxyuridine (FUdR), the deoxynucleoside metabolite of 5-fluorouracil (5 FU), can be converted in a single step to fluorodeoxyuridine monophosphate (FdUMP), which binds covalently to thymidylate synthase (TS). Ribonucleotide reductase, an obligatory enzyme in the synthesis of deoxynucleotides, can be inhibited by hydroxyurea. Recognizing the well-established synergism between 5-FU and folinic acid (leucovorin), we hypothesized that the simultaneous administration of FUdR, leucovorin, and hydroxyurea might afford more effective inhibition of TS. Thirty-six patients with neoplastic disease considered refractory to standard therapy were entered into this phase I protocol. Treatment was administered on days 1 through 5 of a 28-day cycle and consisted of folinic acid (500 mg m-2 day-1) and FUdR at escalating doses of 0.1, 0.15, or 0.2 mg kg-1 day-1 both administered by continuous i.v. infusion, and hydroxyurea given p.o. once per day at doses ranging from 0 to 250o mg in 500-mg increments. The hydroxyurea and FUdR levels were escalated in a sequential fashion. The majority of patients had refractory breast or lung cancer. Dose-limiting toxicities were mucositis and diarrhea at the maximally tolerated dose of 0.15 mg/kg FUdR and 2000 mg hydroxyurea per day in conjunction with high-dose folinic acid. Hematological toxicity was minor. Of the 18 patients in whom response could be evaluated, none had evidence of objective disease regression. Mucositis and diarrhea are the dose-limiting toxicities when continuous infusions of FUdR and high-dose folinic acid are combined with oral hydroxyurea, effects that are consistent with the observed toxicities for FUdR when administered alone or in combination with leucovorin. PMID- 7987995 TI - Vincristine with high-dose etoposide in advanced breast cancer: a phase II trial of the Piedmont Oncology Association. AB - Vincristine (VCR) and etoposide (VP-16) have been shown to be synergistic in a murine model, and this combination was studied in a phase II trial. Eligibility required measurable disease, a performance status of 0-2, a life expectancy of > or = 2 months, an interval of at least 3 weeks since the receipt of previous radiation therapy or chemotherapy and recovery from related toxicity, no prior treatment with VCR or VP-16, and no more than two prior chemotherapy regimens (only one for treatment of metastatic disease). Treatment consisted of 0.5 mg i.v. (bolus) VCR followed by 200 mg/m2 VP-16 given over 2 h. Both drugs were given daily for 3 consecutive days every 3 weeks (total dose: VCR, 1.5 mg; VP-16, 600 mg/m2). A total of 18 patients with metastatic breast cancer were accured; 14 had adjuvant chemotherapy and 8 had chemotherapy for advanced disease. As judged by International Union Against Cancer (UICC) criteria, one complete response (CR) and three partial responses (PR) were obtained, for a CR + PR rate of 22% (95% confidence interval, 6%-48%). All responders had soft-tissue involvement only. Six patients had stable disease and 8 showed progression. The median time to treatment failure was 3.5 months, and the median survival from study entry was 8.3 months. The major toxicity was myelosuppression, with 9 patients (50%) experiencing a total WBC of < 1,000/mm3. Grade 2-3 neurologic toxicity was noted in 6 patients (33%) and grade 3 nausea and vomiting was noted in 5 (28%). The combination of VCR and VP-16 is active in advanced breast cancer but is not convincingly superior to either of these agents used alone. PMID- 7987996 TI - Preclinical pharmacology of 1069C85, a novel tubulin binder. AB - The compound 1069C85, methyl N-[6-(3,4,5-trimethoxybenzyloxy)imidazo(1,2b) pyridazin-2-yl ] carbamate, is a novel synthetic tubulin binder currently undergoing phase I clinical trial. It was developed with a view to overcoming multidrug resistance and is given orally. Cytotoxicity studies in vitro against human ovarian carcinoma cell lines showed a lack of cross-resistance with cisplatin and no cross-resistance in two doxorubicin-resistant cell lines that exhibit high levels of resistance to both paclitaxel and vinblastine. Pharmacokinetic studies in BALB/c mice showed the oral bioavailability to be 20%, with 35% of the drug being excreted unchanged in the faeces over the first 24 h. Maximal plasma concentrations (Cmax) were achieved within 2 h of oral administration as compared with 7.5 min following i.v. injection. At a dose of 20 mg/kg, the tumour drug concentration exceeded the plasma Cmax by a factor of 1.5 and was within the in vitro cytotoxic concentration range. The drug showed a linear relationship between the dose and the area under the plasma concentration versus time curve (AUC) for doses of up to 20 mg/kg, above which no further increase in AUC was observed, possibly due to saturable absorption. 1069C85 is highly protein-bound (85%-99%) and appears to be subject to metabolism. The demonstration of cytotoxic activity against multidrug-resistant human tumour cell lines and the detection of potentially cytotoxic levels in an experimental tumour following oral administration support the choice of 1069C85 for clinical development. PMID- 7987997 TI - A phase I/II study of 4'-O-tetrahydropyranyl-doxorubicin, 5-fluorouracil, and high-dose leucovorin as first-line therapy in advanced breast cancer patients. AB - A total of 50 patients were treated weekly with 5-fluorouracil (FU), leucovorin (LV), and 4'-O-tetrahydropyranyl-doxorubicin (THP) as first-line chemotherapy for advanced breast cancer (ABC). In phase I the doses of LV (500 mg/m2, day 1) and FU (350 mg/m2, day 1) were held constant, while the dose of THP (day 1) was escalated, from the initial dose of 10 mg/m2 up to the maximum tolerated dose (MTD). Twenty-eight patients entered phase I, and MTD for THP was defined as 35 mg/m2 in this combination. Dose-limiting toxicities were myelosuppression and hepatotoxicity. In phase II, another 22 patients were treated with THP at a dose level of 30 mg/m2. Including 4 patients already treated at this dose in the first part, 25 patients were evaluable for response: 1 patient obtained a complete response (CR) and 13 showed a partial response (PR), giving an objective response rate of 56%. The median duration of response was 9.1+ months and median survival, 15.5+ months. Side effects were generally mild, with ECOG grade I and II leukopenia in 51% of all cycles and grade III in 3% of the courses. Other toxicity included nausea and vomiting (54% and 8%, respectively) and alopecia (24%), all restricted to ECOG grade I and II. Our results suggest that weekly THP/LV-FU represents an active regimen for first-line treatment of ABC with relative low toxicity. PMID- 7987998 TI - Validation of a limited sampling model for carboplatin in a high-dose chemotherapy combination. AB - A limited sampling model for the estimation of the carboplatin area under the concentration versus time curve (AUC), as developed by Sorensen et al., was validated prospectively for the use in a high-dose combination chemotherapy schedule. The model allows an estimation of the AUC on the basis of only one timed plasma drug concentration, sampled at exactly 2.75 h after a 1-h carboplatin infusion. Pharmacokinetic curves were obtained from nine patients receiving carboplatin (400 mg/m2 per day) combined with cyclophosphamide (1500 mg/m2 per day), thiotepa (120 mg/m2 per day), and mesna (3 g/day) for 4 consecutive days. Peripheral blood stem-cell transplantation (PBSCT) was performed 3 days later to restore hematopoiesis. Using this combination of high doses, the model proved to be unbiased (MPE -3.40%; SE, 1.22%) and highly precise [root mean squared prediction error (RMSE), 5.15%; SE, 0.17%] for estimation of the AUC during 4 consecutive days. The validated limited sampling model provides a starting point for future pharmacokinetic studies in a larger population of patients, which might lead to more insight into the relationships with the pharmacodynamic outcome of carboplatin and may help in achieving more rational dosing of patients on the basis of an AUC determination. PMID- 7987999 TI - Comparison of the protective effects of desferrioxamine and ICRF-187 against doxorubicin-induced toxicity in spontaneously hypertensive rats. AB - Since the iron-mediated formation of free radicals is considered to be a critical factor in the pathogenesis of the toxicity of doxorubicin (DXR), comparisons were made of the protective effects of two iron chelators, ICRF-187 and desferrioxamine (DFO), against the chronic cardiac and renal toxicity induced by DXR in spontaneously hypertensive rats (SHR). Two preparations of DFO were studied: DFO mesylate (DFO-M) and a polymeric form (DFO-P) in which DFO is conjugated to hydroxyethyl starch. Groups of 5 SHR each were given 12 weekly i.v. injections of 1 mg/kg DXR either alone or 30 min after the i.p. injection of 25 mg/kg ICRF-187, 50 mg/kg DFO-M, 50 mg/kg DFO-P, or 100 mg/kg DFO-P. A semiquantitative assessment was made of the cardiomyopathy (Billingham scale) and nephropathy. Renal protection was minimal with DFO-M and moderate with ICRF-187 and both doses of DFO-P. There was no cardiac protection with DFO-M. Both doses of DFO-P provided similar but modest degrees of cardiac protection. DXR-induced mortality was not prevented by either preparation of DFO. ICRF-187 provided a higher degree of protection against the cardiotoxicity and the mortality induced by DXR. Since both DFO and ICRF-187 are highly efficient chelators of iron in vitro, the differences in their in vivo protective effects are thought to be related to their cellular uptake and intracellular distribution and to the relative availability of different intracellular iron pools to these agents. PMID- 7988000 TI - Early language screening in city and Hackney: the concurrent validity of a measure designed for use with 2 1/2-year-olds. AB - This paper reports data relating to the development of a screening test for language impairment in 2 1/2-year-old children. The screening test itself has previously been described. The results of a pilot study and a larger community study are reported. In all, 34 children were included in the pilot study and 1015 in the community study. The reference test selected was the Reynell Developmental Language Scales and the cut-off adopted 1.5 standard deviations below the mean for either the expressive or the receptive scale of the test concerned. The pass mark on the screening test was ascertained using receiver operating characteristics (ROC). The validity is reported given the cut-off identified. The specificity, sensitivity and both positive and negative predictive abilities are reported for both the pilot and the subsequent study. The application of the test is discussed in the context of the current debate about early identification. PMID- 7988001 TI - Siblings of a child with cancer. AB - A total of 21 healthy siblings were interviewed about their experiences when a brother or sister is diagnosed with cancer. Information about the illness, opinions about who should inform siblings, social support, specific worries and worst memories were studied, as well as perceptions of any differences in the way they were treated by their parents. A short General Impact Scale was developed to assess the extent to which the siblings felt their lives had been disrupted by the illness. Results on these measures were compared with scores on four dimensions of the Sibling Perception Questionnaire (Carpenter & Sahler 1991). Siblings who reported some positive effects as a consequence of the illness (they had become more empathic toward others, or valued life more) perceived their interpersonal relations to be more negatively affected, i.e. there were greater difficulties in their relationships with others especially their parents. Higher scores on communication were related to less of an impact of the illness on life generally. However, these siblings also reported heightened concerns that their brother or sister might die. The data suggested that siblings should have opportunities to talk about implications of the disease, especially worries about death, and more efforts should be made to prepare siblings for visits to hospital and seeing the sick child. PMID- 7988002 TI - Infant crying patterns in Manali and London. AB - This study sought to assess the generalizability of the crying 'peak' previously found in Western infants at around 6 weeks of age. To this end, maternal reports and audiorecordings were used to compare the crying patterns of 2, 6 and 12-week old infants in two cultures expected to differ in their approaches to babycare. As anticipated, Manali mothers were less inclined to leave their babies to cry, took them into their own beds more often, were more likely to be breastfeeding and breastfed their babies to an older age. In spite of these differences, both Manali and London mothers reported their babies to have an evening crying peak, most pronounced at 6 weeks, during this age-range; indicating that this is a general feature of infant development rather than a reflection of Western methods of babycare. Although the maternal reports suggested lower incidences of crying in the Manali infants, the study failed to produce convergent, tape-recorded evidence that this was the case. The definitional and methodological implications of the findings are discussed. PMID- 7988003 TI - Language development in a non-vocal child. AB - Many children who cannot speak, comprehend both oral and written language. Having knowledge of language is not the same as being able to use language for social transactions. Non-vocal children learn to use augmented and assisted systems, but they experience specific difficulties in initiating and maintaining conversations and making use of the pragmatic functions of language. The purpose of this study was to investigate the semantic and syntactic knowledge of a child with severe multiple disabilities who can read and write and comprehend two languages, but does not initiate conversation. The study demonstrates that high levels of language comprehension and ability to read and write do not automatically transfer to conversational competence or narrative ability. PMID- 7988004 TI - The availability of advice regarding infant feeding to immigrants of Vietnamese origin: a survey of families and health visitors. AB - Since their arrival in Britain most Vietnamese mothers have abandoned traditional infant feeding practices for 'modern' methods which are unsatisfactory and expensive. Health staff are not perceived as a source of information or support. This paper emphasizes the need for culturally sensitive initiatives to reverse this trend. PMID- 7988005 TI - Using a hospitalized population to establish reference intervals: pros and cons. PMID- 7988006 TI - Reference intervals developed from data for hospitalized patients: computerized method based on combination of laboratory and diagnostic data. AB - We utilized the databases of a hospital information system to select for determination of reference values various individual hospitalized patients on the basis of their diagnoses at discharge. The nonparametric 2.5-97.5% "health related" reference intervals were calculated for hemoglobin concentration, mean corpuscular volume (MCV), and erythrocyte count for both sexes. After excluding patients with diseases possibly affecting erythrocyte variables, we obtained a final group of 1786 women and 1450 men, ages 20-65 years, who were studied in age groups of 20-30, 30-45, 45-55, and 55-65 years. The upper reference limits of the MCV results obtained from hospitalized patients were higher than those produced conventionally from healthy individuals, as would be intuitively suggested by clinical experience. This method, based on selection by diagnosis, could be applicable to various analytes measured in hospital laboratories, provided sufficient data are available as databases. PMID- 7988007 TI - Verification of reference ranges by using a Monte Carlo sampling technique. AB - We have investigated the application of Monte Carlo significance tests to the verification of reference ranges in the context of the transfer of an established range from one laboratory to another. Here we present an introduction to the Monte Carlo technique, outline a procedure for performing these tests using a commercially available software program, and demonstrate some of the operating characteristics of the tests when they are used to compare samples of different sizes and variances. PMID- 7988008 TI - External quality assessment in primary health care by using fresh whole blood. AB - Desktop analyzers and single-test meters used in primary healthcare are mainly calibrated to measure whole blood. To minimize matrix effects of control materials in external quality assessment schemes, we stabilized fresh human EDTA treated blood with sodium iodoacetate (1.8 mmol/L). The whole-blood based control material was useful for control of hemoglobin and glucose, the two most common analyses in primary care, even after storage at room temperature for at least 10 days and at 5 degrees C for 3 weeks. The material was also useful for control of cholesterol and creatinine analyses for samples stored as long as 3 days at ambient temperature. PMID- 7988010 TI - Detergent extraction and enzymatic analysis for fecal long-chain fatty acids, triglycerides, and cholesterol. AB - We report a procedure for determining fecal long-chain fatty acids (LCFA), triglycerides, and cholesterol after detergent extraction with 10 mL/L Triton X 100, 6 mL/L Brij 30, and 0.1 mol/L HCl in isotonic saline by enzymatic analysis of the extraction supernates. Mean recoveries of calibrators ranged from 105% to 117%. Assays of fecal extracts were linear with concentration from 0 to 1000 mumol/L for LCFA, from 10 to 90 mumol/L for triglycerides, and from 0 to 300 mumol/L for cholesterol. Within-run CVs were < 3% for medium and high concentrations, and 3%, 14%, and 28% for low concentrations of LCFA, cholesterol, and triglycerides, respectively. Correlation with gravimetric determination resulted in coefficients (r2) of 0.72 for total fat, 0.63 for neutral fat, and 0.66 for nonesterified fat. Assays of extracts and residues prepared for gravimetric determination indicated that approximately 90% of triglycerides, cholesterol, and LCFA were extracted by organic solvents and that the extracts contain a significant amount of other fats. The proposed method appears accurate, precise, specific, and suitable for routine analysis. PMID- 7988009 TI - Simple and rapid detection of cholesteryl ester transfer protein deficiency by using nonradioisotopic single-strand conformation polymorphism analysis. AB - We developed a polymerase chain reaction (PCR)-single-strand conformation polymorphism (SSCP) analysis technique by using silver staining to detect the G- >A point mutation of intron 14 of the cholesteryl ester transfer protein (CETP) gene, which is a common mutation in CETP deficiency. After conventional PCR, amplified DNA was heated and subjected to electrophoresis in polyacrylamide gel containing glycerol. The gel was then stained with silver to identify DNA bands. With this technique, we examined 40 subjects with high concentrations of high density lipoprotein cholesterol (> or = 1 g/L) and found one homozygote and eight heterozygotes. The procedure is suitable for screening because it is quick and does not require radioactive materials or restriction enzymes. PMID- 7988011 TI - Determination of a T/G polymorphism at nucleotide 3206 of the apolipoprotein C III gene by amplification refractory mutation system. AB - We used the amplification refractory mutation system (ARMS)--a polymerase-chain reaction-based method--to determine the 3206 T-to-G polymorphism on exon 4 of the apolipoprotein (apo) C III gene. Apo C III is an inhibitor of the enzyme lipoprotein lipase (EC 3.1.1.34). Previous studies have demonstrated that a polymorphism at nucleotide 3175 on exon 4 of this gene is associated with hypertriglyceridemia. We studied 45 hypertriglyceridemic and 46 age-matched controls for the 3206 T-to-G polymorphism. The results showed a significant difference in the distribution of the genotypes with respect to this allele between the hypertriglyceridemic and control individuals. We also determined the presence of the SacI site at nucleotide 3175 in these same individuals and found no significant difference in SacI genotypes between the two groups. This study reaffirms the usefulness of ARMS as a simple, reliable method for detecting mutations and polymorphisms in clinical and epidemiological studies. PMID- 7988012 TI - Metabolic determinants of the course of coronary artery disease in men. AB - We examined associations between metabolic variables and changes in coronary artery disease (CAD) in the St. Thomas' Atherosclerosis Regression Study (STARS). The course of CAD over 3 years was measured continually by quantitative coronary angiography, i.e., as the per patient change in the mean absolute width of coronary segments (delta MAWS). The decrease in MAWS (progression of CAD) was significantly correlated with in-trial plasma concentrations of cholesterol (P = 0.002), low-density lipoprotein (LDL) cholesterol (P = 0.001), apolipoprotein B (apoB) (P = 0.008), and lipoprotein(a) [Lp(a)] (P = 0.004); no significant associations were found with high-density lipoprotein (HDL) cholesterol, apoA-I, vitamin E, thyroid hormones, fibrinogen, von Willebrand factor, or post-load plasma glucose and insulin concentrations. By multiple regression analysis, LDL cholesterol was the best predictor of delta MAWS, the adjusted model explaining 22% of the variance (P = 0.04). Thus, in men with symptomatic CAD the most important metabolic predictor of change in CAD is plasma LDL cholesterol, there being no advantage in measuring other variables, in particular, apoB or Lp(a). PMID- 7988013 TI - Detection of alpha-thalassemias by multiplex polymerase chain reaction. AB - Although alpha-thalassemia is the most common genetic abnormality in the world, there is currently no routine laboratory method to definitively identify individuals who are affected. We describe a rapid and simple method that utilizes deletion-sensitive primers to amplify normal DNA sequences. Deletions involving the regions responsible for most of the alpha-thalassemia cases in the US prevent amplification with these primers. In tests with DNA isolated from small amounts (10 microL) of whole blood, the deletion-sensitive primers gave rise to the expected 248- and 375-bp (base pair) amplification products in normal individuals. These primers, along with primers designed to bind to a nonaffected control sequence from the hemoglobin beta chain, could be amplified simultaneously (multiplex polymerase chain reaction). This made it possible to detect heterozygotes for alpha-thalassemia-2 (one alpha locus deleted) by determining the ratios of the 248- and 375-bp amplification products to the product of the control sequence (268 bp). The method is rapid and simple and can be performed in a routine clinical laboratory. PMID- 7988014 TI - Analysis of fatty acid oxidation intermediates in cultured fibroblasts to detect mitochondrial oxidation disorders. AB - We describe a method for the diagnosis of mitochondrial fatty acid oxidation disorders that is based on the analysis of acylcarnitine and acyl-coenzyme A (acyl-CoA) esters generated during fatty acid oxidation by permeabilized skin fibroblasts. This method requires only small amounts of cultured fibroblasts with minimal preparation, and no isolation of mitochondrial fractions is necessary. During oxidation of [U-14C]hexadecanoate, normal human fibroblasts from patients with fatty acid oxidation defects show a completely different pattern of intermediates, and in each case the observed profile reflects the site of the defect. The diagnosis and likely site of a mitochondrial fatty acid oxidation defect can be made readily from two 80-cm2 culture flasks of fibroblasts with this technique. PMID- 7988015 TI - Establishment of creatinine clearance reference values for older women. AB - Age-adjusted reference ranges for creatinine clearance were determined in 279 women, ages 40-95 years, who were housed in a metabolic research unit and consumed a meat-free diet. Creatinine clearance, but not serum creatinine, declined with age by 0.63 mL/min per 1.73 m2 per year. Serum and urine creatinine concentrations, used to calculate clearances, were analyzed by a kinetic Jaffe procedure. In a subset of 100 subjects, fasting serum creatinine values averaged 8.3 +/- 5.2 (SD) mumol/L higher when measured by the kinetic Jaffe procedure than by an enzymatic method (creatinine PAP). The Cockcroft-Gault formula for estimating creatinine clearance from serum creatinine in women was validated, and the modification factor for the male equation was determined to be 0.84 (95% confidence interval 0.83-0.86) confirming the suggested 15% correction. A prediction formula derived from this population was similar in accuracy to the Cockcroft-Gault formula. PMID- 7988016 TI - Urea and lactate determined in 1-microL whole-blood samples with a miniaturized thermal biosensor. AB - A miniaturized flow-injected thermal biosensor was developed for the determination of urea and L-lactate in undiluted blood in 1-microL samples. The sensor employed a small enzyme column constructed of stainless steel tubing and microbead thermistors. Urease and lactate oxidase/catalase were separately immobilized onto controlled-pore glass beads, which, in turn, were charged into the enzyme column. With a flow rate of 70 microL/min, linear analytical ranges from 0.2 to at least 50 mmol/L and 0.2 to 14 mmol/L were obtained for urea and lactate, respectively. The relative standard deviations (CVs) for measurements of analyte in buffer were 0.91% for urea and 1.84% for lactate. For urea in whole blood, the CV for 50 determinations was 4.1%. Contrived samples containing various concentrations of urea and L-lactate in whole blood were determined with this sensor and with a spectrophotometric method. Comparisons of the results gave correlation coefficients of 0.989 and 0.984 for 30 blood urea and 30 blood lactate assays in concentrations ranging from 4 to 20.9 mmol/L and from 1.7 to 12.7 mmol/L, respectively. PMID- 7988017 TI - Hirsutism and acne in women: coordinated radioimmunoassays for eight relevant plasma steroids. AB - We developed and validated a coordinated set of RIAs for the following eight steroids in single small aliquots (< or = 1 mL) of plasma: androstenedione, dehydroepiandrosterone, 11-deoxycortisol, 21-deoxycortisol (21-DF), 11 beta hydroxyandrostenedione, 17 alpha-hydroxypregnenolone (17-Hpreg), 17 alpha hydroxyprogesterone, and testosterone. Samples were extracted and then chromatographed on celite microcolumns. Radioiodinated tracers were used for two of the assays (17-Hpreg and 21-DF). Tritiated tracers and scintillation proximity assay counting were used to give separation-free procedures for the other six assays, which considerably improved their practicability and reproducibility. The basal and postadrenocorticotropic hormone plasma values for these steroids in normal women sampled in the follicular phase are presented. Finally, the measurement of the eight steroids as a diagnostic method is evaluated with reference to data from 203 patients with hirsutism and (or) acne. PMID- 7988018 TI - Libyan family with hypercholesterolemia and increased high-density lipoprotein cholesterol in plasma. AB - Genetic deficiencies of cholesteryl ester transport protein (CETP) and hepatic lipase activities have been associated with hyperalpha-lipoproteinemias. Here we present a family of 11 members, of which 9, including the father, mother, 5 sons, and 2 daughters, show a marked increase in high-density lipoprotein (HDL) cholesterol alone with low plasma concentrations of triglycerides. Analyses of lecithin:cholesterol acyltransferase (LCAT) activity, cholesteryl ester transfer between HDL fractions, hepatic lipase (HL) activity, and lipoprotein lipase (LPL) activity in these cases showed that a decrease in the heparin-releasable HL activity was the possible cause of the marked increase of HDL2 fractions observed in nine of them. Such a defect in HL activity could significantly affect HDL metabolism in particular and lipoprotein metabolism in general. Evidently, a marked increase in serum total cholesterol due to abnormal metabolism of HDL cholesterol, separate from known causes of altered low-density lipoprotein cholesterol metabolism, e.g., a clearance or a receptor defect, is not uncommon. The coordinated action of HL, LCAT, LPL, and CETP may be essential for normal metabolism of plasma lipoproteins. PMID- 7988020 TI - Early adventures with NMR and clinical chemistry. PMID- 7988019 TI - Improved methods for detecting beta-core in normal and cancer patient urines. PMID- 7988021 TI - Restandardized IMx CA 125 assay: does reference interval need readjustment? PMID- 7988022 TI - Artifacts in measurements of creatinine, sodium, and phosphate from contamination with hydrocortisone sodium succinate. PMID- 7988023 TI - Precautions in using an internal standard to measure pyridinoline and deoxypyridinoline in urine. PMID- 7988024 TI - Iatrogenic hyperthyroidism of long duration in an individual with thyroxine binding globulin deficiency. PMID- 7988025 TI - Relation between age and hair strontium in a population from the Dalian District of China. PMID- 7988026 TI - Analytical interference caused by incompletely clotted serum specimens. PMID- 7988027 TI - Glucose interference in Jaffe creatinine method: effect of calcium from peritoneal dialysate. PMID- 7988028 TI - Thyroid hormone autoantibodies in patients with Graves' disease: effect of anti thyroid drug treatment. AB - We examined the effects of anti-thyroid drug treatment on serum autoantibodies against thyroid hormones (thyroid hormone autoantibodies, THAA), thyroglobulin (Tg) and thyroid peroxidase (TPO) in patients with Graves' disease by measuring each autoantibody level before and after treatment. Six patients among 40 untreated patients with Graves' disease had anti-thyroxine (T4) antibodies. One patient had both anti-T4 and anti-triiodothyronine (T3) antibodies. Thus the prevalence of THAA in untreated Graves' disease was 7 out of 40 (17.5%). Changes in T4-Ab levels after treatment varied. In five cases (cases 3-7) levels decreased 4-7 months after treatment. However, in the other two cases levels fluctuated 1, 3, 6 and 12 months after treatment. None of the previously THAA negative patients became positive after treatment. Anti-Tg antibody (Tg-Ab) was positive in 34 out of 40 (85%) untreated cases and its level decreased in both THAA positive and negative patients after treatment. Anti-thyroid peroxidase antibody (TPO-Ab) was positive in 32 of the 40 (80%) untreated Graves' patients and its level significantly decreased after treatment. Our findings suggest that treatment with anti-thyroid drugs does not produce THAA in Graves' disease. PMID- 7988029 TI - Tubular nephrotoxicity after cardiac surgery utilising cardiopulmonary bypass. AB - Markers of renal tubular injury were examined in 21 patients (16 male, 5 female, mean age 57.4 years) undergoing cardiac surgery utilising cardiopulmonary bypass. Postoperative urine outputs were very high (200-250 ml/h at 1-2 h), decreasing to 100 ml/h by 6 h. Although creatinine clearances did not vary significantly in the postoperative period (P = 0.16), significant changes were noted in the urinary concentrations of three tubular markers relative to creatinine concentration (P < 0.001). Urinary beta 2-microglobulin increased from negligible levels (median 0.01 mg/mmol creatinine) to peak at 4 h (median 4.55 mg/mmol), in part due to interference with its reabsorption by the plasma volume expander Haemaccel. Concentrations of the brush border antigen adenosine deaminase binding protein increased 6-fold, from a median of 5.03 arbitrary units (AU)/mumol to 31.2 AU/mumol at 48 h. The lysosomal enzyme N-acetyl-beta-D-glucosaminidase increased nearly 4-fold, from 0.68 units/mmol to 2.64 units/mmol at 48 h. Our results suggest that cardiac surgery utilising cardiopulmonary bypass is associated with acute tubular injury which can occur in the absence of overt changes in creatinine clearance. PMID- 7988030 TI - A new precipitation method with magnetic separation for high-density-lipoprotein cholesterol assay. AB - We describe a new precipitation method for high-density-lipoprotein cholesterol quantitation. The new method uses magnetic force instead of centrifugal force to separate high-density-lipoprotein from other lipoproteins that are fractioned with a precipitating reagent. The reagents used for the new method are the same as those for the conventional method except that magnetizable particles are included in the former. The magnetizable particles are used without any modifications. The correlation between the new and the centrifuge methods with dextran sulfate-magnesium chloride, sodium phosphotungstate-magnesium chloride and polyethylene glycol 6,000 were satisfactory (r = 0.990, 0.997 and 0.997, respectively). The new method, which can be combined with any precipitating reagents used in conventional methods, is very simple to perform and does not need any special equipment. PMID- 7988032 TI - Modulation defect of sodium pump evidenced in diabetic patients by a microcalorimetric study. AB - Sodium pump activity of intact erythrocytes in their own plasma was measured by microcalorimetry in 41 healthy subjects and 35 insulin-dependent diabetic patients. Results show that modulation of the sodium pump is altered in diabetic patients. Addition of insulin increases functioning of the Na(+)-K+ pump in controls but has no effect in diabetic patients. These subjects show a slower response of the Na(+)-K+ pump to the inhibitory effect of ouabain. Cross incubation experiments suggest that these findings may be explained by the existence of a plasmatic factor that impairs the modulation of the sodium pump in diabetic patients. PMID- 7988031 TI - Cathepsin B and N-acetyl-beta-D-glucosaminidase in human synovial cells in culture: effects of interleukin-1. AB - Human synovial cells were cultured in vitro and tested for the activities of two lysosomal enzymes, cathepsin B and N-acetyl-beta-D-glucosaminidase (NAGA) under various conditions. Unstimulated synovial cells display intracellular and extracellular activities of both enzymes. However, cathepsin B was secreted in a latent pepsin-activatable form, whereas NAGA was secreted in an active form. Most of the cell strains analysed secreted rather limited amounts of the enzymes (less than 25% of total activity); some strains, however were highly secretory, the secreted activity reaching up to 50% of total activity. Cells were then stimulated with human recombinant interleukin-1 alpha (rhIL-1 alpha) or beta. Only the levels of secreted NAGA were clearly increased. Results are to be interpreted in view of the role played by synovial cells and by the lysosomal enzymes they release in inflammatory joint diseases and it would be worthwhile in the future to check for secreted NAGA in various body fluids, such as the synovial fluid of the inflamed joint. PMID- 7988033 TI - Lipoprotein profiling by high performance gel chromatography. AB - High performance gel chromatography (HPGC) was used to separate lipoproteins on the basis of their size and to generate lipoprotein profiles for plasma collected from patients with different lipoprotein phenotypes. These profiles provided a direct measurement of low density lipoprotein (LDL)-cholesterol which was more precise than LDL-cholesterol values calculated by the Friedewald equation. In addition, LDL-cholesterol concentrations were obtained in patients with combined hyperlipidemia in whom LDL-cholesterol could not be accurately calculated by the Friedewald equation. The response of LDL-cholesterol to the drug gemfibrozil was reliably monitored and in addition changes in LDL particle size could be assessed from the LDL apolipoprotein B/cholesterol ratio. HPGC also assisted in the diagnosis of type III hyperlipidemia by revealing a characteristic lipoprotein profile. HPGC-derived lipoprotein profiles provided additional useful clinical information for combined hyperlipidemia (Fredrickson lipoprotein phenotypes IIb, III). PMID- 7988034 TI - Interaction of beta-cyclodextrin with bile acids and their competition with vitamins A and D3 as determined by 1H-NMR spectrometry. AB - The interaction of beta-cyclodextrin (beta-CD) with four bile acids, cholic, taurocholic, chenodeoxycholic and lithocholic, was demonstrated by proton-NMR spectroscopy. Lithocholic and chenodeoxycholic acids exhibit a stronger affinity for beta-CD than cholic and taurocholic acids. The affinity of bile acids for beta-CD increases in relation to their hydrophobicity. The competition between these bile acids and the lipophilic vitamins A and D3 in the formation of beta-CD inclusion complexes was studied. These vitamins compete with cholic and taurocholic acids whereas they do not with lithocholic and chenodeoxycholic acids. In the latter case all of the beta-CD present was consumed by the bile acids with the vitamins remaining free in the medium. The affinity of vitamins A and D3 for beta-CD is lower than that of the bile acids. Therefore, when lithocholic or chenodeoxycholic acids are present, the formation of beta-CD inclusion complexes with the vitamins does not occur. The results of this study suggest that depletion of lipophilic vitamins will not occur upon ingestion of beta-CD, thus providing further support for the safety and suitability of beta-CD as an ingredient in foods and orally administered drugs. PMID- 7988035 TI - Characterization of tumor-associated antigen (2H6 antigen) defined by monoclonal antibody 2H6. PMID- 7988036 TI - Serum type IV collagen and prolyl hydroxylase levels: effect of gender and age. PMID- 7988037 TI - Estimation of pS2 protein level in human body fluids by a sensitive two-site enzyme immunoassay. AB - A sensitive two-site enzyme immunoassay (EIA) system was established for human pS2 protein, a small estrogen-inducible secretory protein of unknown function originally identified in MCF-7 human breast cancer cells. Our EIA system is based on the sandwiching of antigen between anti-recombinant (r) pS2 antibody IgG coated on a polystyrene plate and biotinylated anti-rpS2 antibody IgG. The amount of pS2 protein was quantified by measurement of the bound enzyme activity of subsequently added streptavidin-linked beta-D-galactosidase (beta-D galactosidase, EC 3.2.1.23). pS2 protein purified from MCF-7 culture supernatants was detectable at a concentration as low as 3 pg/ml (corresponding to 60 fg/well). This EIA system revealed that the amount of pS2-like immunoreactivity (LI) in human urine was 13.6 ng/mg creatinine (median, n = 416) and that there was no correlation between the pS2-LI concentration in urine and sex or aging. pS2-LI levels in plasma and sera of the normal subjects were 392 pg/ml (median, n = 14) and 494 pg/ml (median, n = 12), respectively. The serum level of the patients with breast cancer (528 pg/ml; median, n = 67) was not statistically different from that of normal subjects, although high levels of pS2 protein in breast cancer tissues had been reported. PMID- 7988038 TI - A detection method for point mutation in the precore region of human hepatitis B virus (HBV)-DNA using mutation-site-specific assay. AB - In the natural progression of acute active hepatitis and chronic active hepatitis in human hepatitis B virus (HBV)-infected patients, inactive hepatitis develops by seroconversion, which can be explained by the disappearance of HBe antigen. However, it has been found that in some patients with hepatitis, alanine aminotransferase levels undergo fluctuation even though their serum is negative for HBe antigen. In these patients, HBV-DNA has been detected in the serum and the HBV-DNA so detected has been considered a cause of worsening liver function. Most HBV-DNA detected in these cases has a point mutation from G to A at the 83rd base in the precore region. As a result of this point mutation, HBV is unable to produce HBe antigen. We have devised a sensitive polymerase chain reaction (PCR) method, a mutation-site-specific assay, for the detection of point mutations at the 83rd base in the precore region using a specific mutation-trapped oligonucleotide primer for the mutant HBV genome. PMID- 7988039 TI - Elevation of serum group II phospholipase A2 levels in patients with advanced cancer. AB - To investigate the role of group II phospholipase A2 (M-PLA2) in cancer, we examined M-PLA2 serum levels in 170 pre-operative patients with various cancers and found elevated levels in 49% of them. M-PLA2 serum levels were significantly higher in patients with tumor stages T2-4, N1, M1 and stages II to IV than in T1, N0, M0 and stage I tumors, respectively. In all nine post-operative patients tested, M-PLA2 decreased 14 days after tumor resection and reduced to normal levels in 4 patients. Six of 16 carcinoma cell lines (37.5%) spontaneously secreted M-PLA2 into the culture supernatant despite the absence of IL-6 and IL-1 in 5 of the 6 lines. These results demonstrate that M-PLA2 produced by cancer cells may contribute, at least in part, to the elevation of serum M-PLA2 levels observed in cancer patients. PMID- 7988040 TI - The correlation coefficient in the interpretation of laboratory data. PMID- 7988041 TI - Estradiol receptors in combination with neu or myc oncogene amplifications might define new subtypes of breast cancer. AB - Amplifications of neu and c-myc were evaluated in 218 and 145 breast cancers (BC), respectively. Oncogene amplifications were determined for the most part by Southern blot. An association between the proportion of nodes affected and the intensity of neu amplification in estadiol receptor negative (ER-) BC was found (P = 0.028), which was confirmed by the multi-factor analysis of variance (P = 0.05). A significantly greater incidence in neu amplifications among BC with metastases was also found (P = 0.031). A strong association (P = 0.01) between the neu and myc amplification was observed. There is a strong association between myc amplification and ER- BC (P < 0.01). It is concluded that (1) the combination ER- with neu amplification might define a new group of more aggressive BC, as is suggested by their associated nodal involvement; (2) the linkage of myc amplifications with ER- BC and high grade of neu amplification might reflect a trait of tumor aggressivity. PMID- 7988042 TI - Quantitative and qualitative changes of extracellular-superoxide dismutase in patients with various diseases. AB - Extracellular-superoxide dismutase (EC-SOD) is a secretory glycoprotein that is the major SOD isozyme in extracellular fluids. It has previously been shown that EC-SOD levels in sera from healthy persons are clearly divided into two discontinuous groups: a lower group (named Group I, below 120 ng/ml) and a higher group (Group II, above 400 ng/ml). The family studies have shown that the high EC SOD level in healthy persons is genetically transmitted. We report here on the EC SOD levels in the sera of patients with various diseases. The EC-SOD levels were distinctly higher in patients with renal diseases and moderately higher in liver diseases and diabetes than those in normal healthy persons. In cerebrovascular diseases, heart diseases and acute digestive diseases, significant differences of EC-SOD were not observed. In patients with renal diseases, the increase of EC-SOD was accompanied by the lack of renal function. Serum EC-SOD in Group I healthy persons is known to be heterogeneous with regard to heparin affinity and can be separated into three fractions: A without affinity, B with weak affinity and C with relatively strong heparin affinity, whereas the EC-SOD in Group II is mainly one fraction of C-type. Also in the case of hemodialysis patients, serum EC-SOD in Group I or Group I' (approximately 120-400 ng/ml) was divided into three fractions. EC-SOD in Group II showed two different profiles on heparin-Sepharose column chromatographies: one consisted mainly of EC-SOD C and the other consisted of EC-SOD A and C. It is probable that the high serum EC-SOD level in hemodialysis patients was due to two possible factors: the genetic transmitted factor and unknown pathophysiological factor(s). PMID- 7988043 TI - L-homoserine hydroxamic acid as an antitumor agent. AB - This report confirms the potent mutagenic and antitumor activity of L-homoserine hydroxamic acid in both in vitro and in vivo test systems. Its mutagenic potential is evident in the developing tadpoles of Xenopus laevis eggs exposed to the compound. Cytotoxic effects are demonstrated against human leukemia and melanoma cell lines proliferating in tissue culture and against xenografts of human breast cancer and sarcoma growing in nude mice. We propose that the mutagenic and antitumor activity are mediated through hydroxylamine, which is released from its stable carrier amino acid, homoserine, consequent to a reduction in pH occurring at the cellular level. The cytotoxic effects of L homoserine hydroxamic acid are more intense than those of the D-isomer and are more evident in neoplastic than in normal cell lines. PMID- 7988044 TI - Semi-quantitative latex method for lipoprotein(a) assay. PMID- 7988045 TI - Nicotinic acid phosphoribosyltransferase activity in human erythrocytes: studies using a new HPLC method. AB - A non-radiochemical method linked to reverse-phase high-performance liquid chromatography was developed to determine the activity of nicotinic acid phosphoribosyltransferase (EC 2.4.2.11) in crude lysates of human red blood cells. The method is accurate and easily reproducible in different chromatographic systems. The enzyme activity was determined in erythrocytes of healthy subjects and in patients with different purine disorders showing altered NAD levels. Very low enzyme activity was found in a boy hemizygous for phosphoribosylpyrophosphate synthetase superactivity, consistent with the low erythrocyte NAD concentration. PMID- 7988046 TI - Cardiac myosin light chain-1 release in acute myocardial infarction is associated with scintigraphic estimates of myocardial scar. PMID- 7988047 TI - A combination assay of MB and MM isoforms of serum creatine kinase in acute myocardial infarction. PMID- 7988048 TI - Determination of amyloid type by ELISA using milligram amounts of tissue. AB - A new procedure was developed for isolation and immunochemical identification of amyloid proteins. This procedure involves extraction of amyloid proteins from tissues with aqueous acidic acetonitrile, their purification by HPLC and identification by ELISA. In this way the type of amyloid proteins was defined in amyloid-containing tissues obtained from 15 patients. The technique is simple, rapid and enables typing of amyloid proteins using only milligram amounts of tissue. This is in contrast to the conventional amyloid isolation and chemical identification technique which is laborious, time consuming and requires gram amounts of tissues. The procedure may enable the identification of the type of amyloid in biopsy specimens and thus help in evaluation of prognosis and determination of the therapeutic policy. PMID- 7988049 TI - Serum hyaluronate levels predict responsiveness to interferon alpha therapy in patients with chronic hepatitis C. PMID- 7988050 TI - A simple non-radioactive assay for hemoglobin E gene in prenatal diagnosis. PMID- 7988052 TI - The utilization of intravenously infused pyridoxine in humans. AB - The utilization of a usual dose of intravenously infused pyridoxine (100 mg pyridoxine hydrochloride) was investigated in ten healthy males. Blood plasma and erythrocytes were investigated by means of high-performance liquid chromatography. Detectable metabolites in blood plasma were pyridoxine, pyridoxal 5'-phosphate, pyridoxal and 4-pyridoxic acid. In erythrocytes pyridoxine, pyridoxal 5'-phosphate, pyridoxal, and pyridoxamine 5'-phosphate were found. From their concentration-time curves rate constants of elimination and invasion, volume of distribution (pyridoxine) and the areas under the curves were calculated. Values for concmax and tmax are reported. A comparison with earlier results of oral pyridoxine administration revealed a better utilization after intravenous than after oral application, i.e. a greater build-up of coenzyme forms. A regulatory phenomenon in erythrocytes caused by high doses of pyridoxine is described. In view of the potential toxicity of pyridoxine the doses used in parenteral nutrition are called into question. PMID- 7988051 TI - Serum serotonin, lactate and pyruvate levels in infantile autistic children. PMID- 7988053 TI - Determination of trace amounts of albumin in human bronchoalveolar lavage fluids by fluorometry with chromazurol S. AB - Fluorometry using chromazurole S (CAS) was applied to determine trace amounts of albumin in human bronchoalveolar lavage fluids (BALF). The calibration curve was linear in the range of 5-60 micrograms/ml of albumin. The CAS method was proven to be much more selective for albumin than for IgG. Freezing of BALF samples did not affect albumin analysis by the CAS method after storage at -20 degrees C for 80 days. This finding suggests that albumin in the BALF samples is stable under these conditions. The correlation was highly linear (r = 0.966) between the albumin levels in concentrated BALF samples (n = 47) determined by the CAS method and by radial immunodiffusion. The CAS method is sensitive enough to determine albumin levels in unconcentrated BALF samples, whereas radial immunodiffusion often requires concentration. The former method is more suitable for measuring albumin in BALF samples than the latter, because concentration by ultrafiltration results in poor reproducibility. The concentration of albumin in BALF samples of healthy volunteers (n = 5) and patients with sarcoidosis (n = 32) was determined by the CAS method. There was a statistically significant difference (P < 0.01) in the albumin levels in BALF samples between healthy subjects and patients with sarcoidosis at a clinically active state (n = 15). This finding shows that the determination of albumin levels in BALF samples is useful for investigating lung diseases and that the CAS method is promising in the determination of trace albumin in BALF samples, because it is simple, sensitive and precise. PMID- 7988055 TI - Early changes of serum N-acetyl-beta-glucosaminidase, tissue plasminogen activator and erythrocyte superoxide dismutase in relation to retinopathy in type 1 diabetes mellitus. AB - Biochemical markers of early changes that are characteristic for diabetic microangiopathy are not completely understood. We investigated activities of serum N-acetyl-beta-glucosaminidase (NAG), tissue plasminogen activator and erythrocyte superoxide dismutase in well defined groups of type 1 diabetic patients. Patients were selected on the basis of 4 year follow-up observation. Forty-two type 1 diabetic patients were subdivided into those without retinopathy (n = 13) throughout the study, those with newly developed or worsened retinopathy (n = 12) during 4 years and those with retinopathy already established at the beginning of the study and without evidence of its progression (n = 17). All diabetic patients had albustix-negative urine. A significant increase of the mean serum NAG activity during 4 years was found only in patients without retinopathy (P < 0.01) whereas no changes of the altered enzyme activities were present in patients with developing and established retinopathy. The mean activity of tissue plasminogen activator was elevated in all groups of diabetic patients compared with healthy subjects (P < 0.001). A significant positive correlation was found between plasminogen activator and serum NAG (r = 0.51, P < 0.01). Erythrocyte superoxide dismutase was higher in diabetic patients than in healthy persons (P < 0.01) but no differences were observed between the patients with or without retinopathy. Superoxide dismutase positively correlated with NAG (r = 0.57, P < 0.01). We conclude that early functional changes precede a morphological development of diabetic retinopathy as was evident from the altered enzyme activities. PMID- 7988054 TI - A processing-independent assay for human procholecystokinin and its products. AB - In order to develop a processing-independent analysis for procholecystokinin (proCCK) and its products, antibodies were raised against the synthetic fragment 62-71 of human proCCK. All rabbits (n = 8) responded to the immunization. One (No. 89,009) produced antibodies of particularly high titer (1:350,000), homogeneity (Sips' index approximately 1.0) and binding affinity (K0 eff approximately 0.88 x 10(12) l/mol). A radioimmunoassay using this antiserum and [125I]tyrosine-extended fragment 62-71 measured the total CCK mRNA product after tryptic cleavage at Lys61 in normal and neoplastic tissue independent of the degree of precursor processing. In addition to previously known CCK producing tumors, CCK was found also in a thoracic round-cell tumor (Askin tumor) and in brain tumors (gliomas and astrocytomas). These tumors processed proCCK poorly. Thus, they contained 11 and 23 (mean n = 5) pmol/g of proCCK and its products before, versus 71 and 99 (mean) pmol/g after tryptic cleavage, respectively. Accordingly, gel chromatography revealed significant amounts of unprocessed proCCK, large molecular forms of glycine-extended CCKs and the well-known carboxyamidated and tyrosine O-sulfated bioactive CCK-83, -58, -33, -22 and -8. We conclude that monospecific antibodies directed against the N-terminus of sequence 62-71 of human proCCK are suitable for processing-independent analysis (PIA) for proCCK and its products. Moreover, we suggest that such PIA should be used for quantitation of CCK gene expression at peptide level in normal tissue and tumors. PMID- 7988056 TI - Quantitative computer image analysis of a human chorionic gonadotropin colloidal carbon dipstick assay. AB - Colloidal particles are widely used in qualitative dipstick assays for the determination of various proteins and haptens. Recently, a new colloidal label has been introduced based on elemental carbon. With this carbon label we have prepared a human chorionic gonadotropin-specific dipstick assay with a sensitivity of 10 mIU/ml. In addition, an image- and data-processing procedure for the quantification of the dipstick assay has been developed. The sum of the pixel grey levels of a carbon line was taken as a measure for this quantitative purpose. The measurement range of the assay is almost three orders of magnitude, i.e. 10 mIU/ml to 500 mIU/ml. The deviation from the mean of two dipstick determinations was 1.22% on average. The within-run and between-run precision, expressed as coefficients of variation at 50 mIU/ml were 1.03% and 1.84%, at 150 mIU/ml 2.14% and 3.77% and at 450 mIU/ml 2.55% and 5.28%, respectively. We have correlated this quantitative sol particle immunoassay with a commercial human chorionic gonadotropin specific radioimmunoassay. In an experiment with 25 human urine samples containing the hormone in amounts from 5 to 300 mIU/ml the correlation coefficient was 0.999. The sol particle immunoassay quantified by computer image analysis has been termed Sol particle Image Processed ImmunoAssay (SIPIA). PMID- 7988057 TI - Precipitation procedures used to isolate high density lipoprotein with particular reference to effects on apo A-I-only particles and lipoprotein(a). AB - Analysis of high density lipoprotein (HDL) isolated from serum without major hypertriglyceridaemia and by five different precipitation methods showed that there were no significant differences in total cholesterol and triglyceride concentrations in the HDL supernatants prepared by the different methods but that free cholesterol, phospholipid, apolipoprotein (apo) A-I and HDL particles containing apo A-I but not apo A-II (LpAI) concentrations were significantly lower for heparin-manganese chloride method 2 (final manganese chloride concentration 92 mmol/l) compared with the other methods. Modest differences in HDL cholesterol, apo A-I and LpAI were observed between heparin-manganese chloride method 1 (final magnesium concentration 46 mmol/l) and the dextran sulphate, phosphotungstate and polyethylene glycol 6000 methods. Lipoprotein(a) (Lp(a)) and apo B were undetectable in the HDL supernatants, indicating that apo B-containing lipoproteins including Lp(a) were essentially completely removed by all the precipitation procedures. PMID- 7988058 TI - Differential processing of type I and type III procollagens in the tumour cysts and peritoneal ascitic fluid of patients with benign and malignant ovarian tumours. AB - Progressive ovarian carcinoma induces the synthesis of type I and type III procollagens both in the tumour tissue and in the peritoneal cavity. We studied the processing of these proteins by determining the different antigen forms related to their propeptide parts by gel filtration and subsequent immunological assays. Samples of ovarian cyst fluid and peritoneal ascitic fluid were obtained from patients with benign and malignant ovarian tumours. In both benign and malignant ovarian cysts, the predominant procollagen antigens were the free propeptides, with few or no larger components, indicating efficient processing of types I and III procollagens in the tumour tissue. In ascitic fluid the processing was more variable. The aminoterminus of type III procollagen was partially unprocessed in all samples studied, whereas that of type I procollagen was nearly always completely processed. There was a clear difference between malignant and benign tumours in the processing of the carboxyterminus of type I procollagen: a significant part of the carboxyterminal propeptide antigen was invariably associated with a collagenous domain in malignant tumours, whereas in benign tumours the free propeptide predominanted. The results indicate that interstitial procollagens are effectively processed in the tumour tissue during the fibroproliferative reaction typical of malignant ovarian tumours, whereas the processing of the procollagens released into peritoneal ascitic fluid is incomplete. PMID- 7988059 TI - Measurement of short-chain acyl-CoA dehydrogenase (SCAD) in cultured skin fibroblasts with hexanoyl-CoA as a competitive inhibitor to eliminate the contribution of medium-chain acyl-CoA dehydrogenase. AB - Short-chain acyl-CoA dehydrogenase (SCAD) deficiency has so far been reported in only very few patients. This is due, in part, to the problems involved in measuring the activity of SCAD unequivocally. The main reason for this difficulty is that butyryl-CoA, the substrate preferably used for SCAD activity measurements, is also dehydrogenated by medium-chain acyl-CoA dehydrogenase (MCAD). Elimination of this contribution can be achieved by means of immune precipitation with a specific MCAD antibody. We now describe a relatively straightforward assay based on the use of gas chromatography/mass spectrometry for detection. The contribution of MCAD to overall butyryl-CoA dehydrogenation was eliminated by adding excess hexanoyl-CoA to the assay medium. The validity of the method developed was checked by SCAD-activity measurements in fibroblasts from an established SCAD-deficient patient. PMID- 7988060 TI - A diagnostic approach to pancreatic cancer. AB - The diagnostic and staging evaluation for patients suspected of having pancreatic cancer has not been standardized. This review describes a practical algorithm for the workup of affected individuals. Computed tomography as an initial test can usually provide the most information when clinical features or biochemical or serological (CA19-9) test results suggest the presence of a neoplasm. Endoscopic retrograde cholangiopancreatography is appropriate when scans are equivocal or clearly abnormal especially in jaundiced patients. A cytological diagnosis is possible and biliary decompression can be accomplished with this procedure. Laparoscopy followed by angiography is useful for staging surgical candidates. PMID- 7988061 TI - Alpha-1-antitrypsin deficiency and liver disease. AB - Alpha-1-antitrypsin deficiency is a common autosomal recessive disorder associated with premature development of emphysema, liver cirrhosis and hepatocellular carcinoma. This article reviews the existing literature on alpha-1 antitrypsin deficiency, with an emphasis on recent developments. A description of the protein, gene structure and function of alpha-1-antitrypsin as well as clinical aspects are presented. Treatment issues are addressed and a framework for the diagnostic workup and management of patients with alpha-1-antitrypsin deficiency and chronic liver disease is provided. PMID- 7988062 TI - Hydatid liver disease: a perspective in treatment. AB - Hydatid liver disease caused by Echinococcus granulosus is a serious problem in regions where the parasite is endemic. The treatment of choice is surgery, however, it is associated with recurrence rates of up to 30%. Medical treatment with benzimidazole derivatives has limited success. The treatment modalities for hydatid liver disease are reviewed in detail and are evaluated in terms of radical treatment. PMID- 7988063 TI - Aspirin and neoplasia of the digestive tract: is there a chemopreventive effect? AB - There has been much recent interest in the hypothesis that aspirin and other non steroidal anti-inflammatory agents (NSAIDs) protect against gastrointestinal, particularly colorectal, carcinoma. Three lines of evidence support this hypothesis: First, NSAIDs inhibit the growth of colorecal neoplasms in laboratory rodents. Epidemiological studies in humans also suggest a protective effect. Three case control and two cohort studies have examined the relation between aspirin use and large bowel neoplasia, and four of these five studies found a risk reduction for either incidence or mortality of about 50% in regular users of aspirin. Finally, two small intervention studies in patients with familial polyposis showed a short-term reduction in polyp formation in patients treated with NSAIDs. In contrast, a large randomized trial of aspirin in human subjects detected no reduction in incidence of colorectal carcinoma in those assigned to aspirin compared to placebo. Colorectal cancer is common and an effective primary prevention strategy could lead to significant public health benefits. Further research into the potential of aspirin to achieve this is keenly awaited. It is, however, premature to recommend it specifically for this purpose on the basis of current evidence, given the known adverse effects of aspirin and related compounds, especially on the gastrointestinal tract. PMID- 7988064 TI - Vegetarianism, dietary fibre and gastro-intestinal disease. AB - PURPOSE: To review the association between vegetarianism, dietary fibre and gastro-intestinal disease. DATA: There is an increasing trend towards vegetarianism in the United Kingdom. Studies have shown a lower than expected death rate in vegetarians with a significant association between meat eating and mortality from all causes in men. Vegetarians were found to have a lower incidence of gastro-intestinal cancer, gallstones, diverticular disease and constipation. Patients treated with vegetarian/high-fibre diets have not experienced significant benefits when diets are used in gastro-intestinal cancer, peptic ulcer disease or inflammatory bowel disease. CONCLUSION: The benefits of a vegetarian life-style may be conferred to non-vegetarians by eating a carefully planned non-vegetarian diet consisting of increased fruit, vegetables and fibre. PMID- 7988066 TI - DNA polymorphism at the locus for angiotensinogen I-converting enzyme in Norwegian patients with myocardial infarction and controls. PMID- 7988065 TI - Infertility, obstetric and gynaecological problems in coeliac sprue. AB - There is now substantial evidence that coeliac sprue is associated with infertility both in men and women. In women it can also lead to delayed menarche, amenorrhoea, early menopause, recurrent abortions, and a reduced pregnancy rate. In men it can cause hypogonadism, immature secondary sex characteristics and reduce semen quality. The real mechanism by which coeliac sprue produces these changes is unclear, but factors such as malnutrition, iron, folate and zinc deficiencies have all been implicated. In addition in men gonadal dysfunction is believed to be due to reduced conversion of testosterone to dihydrotestosterone caused by low levels of 5 alpha-reductase in coeliac sprue. This leads to derangement of the hypothalamic-pituitary axis. Hyperprolactinaemia is seen in 25% of coeliac patients, which causes impotence and loss of libido. Gluten withdrawal and correction of deficient dietary elements can lead to a return of fertility both in men and women. PMID- 7988067 TI - Colorectal cancer: lessons for genetic counselling and care for families. AB - Cancers of the colon and the rectum are the second leading cause of malignancy in European countries with similar incidence rates for men and women and, therefore, one of the major health concerns. Emphasis is placed on the early detection of a developing neoplasm in order to improve the life expectancy of patients and their quality of life. Colorectal cancer (CRC) is an excellent model for studying the etiology and pathogenesis of a common malignancy and the complex multistage process of carcinogenesis. Abundant clinical and pathological evidence suggests that CRC arises from benign adenomas that proceed through a series of steps to metastatic carcinomas. Following the discovery of oncogenes and, more importantly tumor suppressor genes, Fearon & Vogelstein (1990) proposed a scheme of genetic events which are associated with colorectal tumorigenesis. Genetic linkage studies have recently identified another type of gene for colon cancer susceptibility that seems to act by destabilising the genome. PMID- 7988068 TI - Complications to the complex inheritance of schizophrenia. PMID- 7988069 TI - The genetic structure of personality and learning: a phylogenetic model. PMID- 7988070 TI - Heredity in personality disorders--an overview. AB - The concept of personality disorders is based on deviant personality traits in both the DSM-III-R and ICD-10 classifications. A diagnosis of personality disorder can be made reliably with structured interviews. Many individuals are diagnosed with more than one personality disorder, and other mental disorders are often found at the same time. Among the 11 personality disorders in DSM-III-R, only the schizotypal, borderline, and antisocial have been examined to any considerable extent for gene effects. The problems of studying heredity are here demonstrated for borderline and antisocial personality disorders. Recommendations are given as to strategies for further study of heredity in personality disorders. PMID- 7988071 TI - Heredity in dementia of the Alzheimer type. AB - Family, twin and linkage studies in Alzheimer's disease are reviewed. Several of these studies appear to be burdened with sources of error, mainly related to sampling and clinical diagnoses. It was previously thought that early-onset cases of Alzheimer's disease were heavily genetically influenced, whereas late-onset cases were sporadic. The author questions whether this difference is mainly due to methodological error. PMID- 7988072 TI - Gene environment interaction and plasma triglyceride levels: the crucial role of lipoprotein lipase. PMID- 7988073 TI - Towards acceptable practices for antenatal and neonatal screening for disease or disease risk. PMID- 7988074 TI - Identification of genetic variation that determines levels of plasma triglycerides and hypercoagulability. PMID- 7988075 TI - Studies on the structure and function of the apolipoprotein(a) gene. AB - Lp(a) is an LDL-like lipoprotein that is a major inherited risk factor for atherosclerosis. It is distinguished from Lp(a) by the addition of apolipoprotein(a). The gene structure of apolipoprotein(a) is homologous to plasminogen, and competition with plasminogen activity may account for some of the pathophysiology associated with Lp(a). Six highly related genes have now been identified, and at least four are found in close proximity in overlapping genomic clones. Studies have begun on the regulation of apolipoprotein (a) gene expression, and the human apolipoprotein(a) gene has been inserted into transgenic mice, where it leads to the development of arterial lesions. PMID- 7988076 TI - Apolipoprotein(a): structural and functional consequences of mutations in kringle type 10 (or kringle 4-37). AB - The size polymorphism of Lp(a) is well recognized. It is now apparent that there is an additional polymorphism resulting from mutations occurring at the kringle level. One of these mutations involves a trp72 to arg substitution in apo(a) kringle type 10 and is attended by a defective binding of Lp(a) to immobilized lysine/fibrin. Other mutations affecting the other amino acids of the "lysine binding pocket" may have similar functional consequences and may be important at the clinical level in terms of thrombogenesis. PMID- 7988077 TI - Importance of Lp(a) lipoprotein and HLA genotypes in atherosclerosis and diabetes. AB - Lp(a) lipoprotein [Lp(a)] was found in previous studies to be independently associated with early atherosclerosis and its sequelae. Lp(a) in vitro bound to glucosaminoglycans and was easily aggregated at physiological Ca2+ concentration, and small Lp(a) aggregates were phagocytosed by macrophages. Lp(a) was also found to be related to carbohydrate metabolism, and increased Lp(a) levels have been described in diabetic patients with clinical complications and were recently found in rheumatoid arthritis patients. In this study of nondiabetic male patients with documented CAD before 50 years of age and controls, a significant correlation was found between Lp(a) and IGF-1 levels. HLA class II DR13 (DR6) was more frequent and DR15 (DR2) was less frequent in patients than in controls. The calculated relative risk for CAD was 4.0 for DR17 (DR3), but the difference was not significant. These differences seem to be related to high Lp(a) levels. It is suggested that phagocytosis of preferably Lp(a) aggregates can induce an immunological tissue response that may contribute in the pathogenesis of Lp(a) associated diseases and may be more prominent in combination with some inherited HLA class II haplotypes. Probably due to sex hormone effects, the association may be most pronounced in young males and in older females. PMID- 7988078 TI - High Lp(a) lipoprotein level in maternal serum may interfere with placental circulation and cause fetal growth retardation. AB - We report on a woman with an Lp(a) lipoprotein level above the 99th centile of the population distribution of concentrations, who at the age of 43 had had deep vein thrombosis causing a pulmonary embolus and whose brother, who also had a very high level, had suffered a cerebral infarction at the age of 43. She had given birth to three children, all with very low birth weight, one of whom died when 3 months old. The placentas had been small and ischemic. The concurrence of a very high Lp(a) lipoprotein level, familial thromboembolic disease and recurrent placental ischemia with delivery of children with low birth weight suggests the possibility that a very high Lp(a) lipoprotein concentration may predispose to placental insufficiency, presumably arising from pathological changes in maternal uterine vessels in the placental bed. If confirmed, a very high Lp(a) lipoprotein level may be a factor to consider in women who have repeated pregnancies with placental insufficiency and who give birth to children with low birth weight. PMID- 7988080 TI - Traversing the biological complexity in the hierarchy between genome and CAD endpoints in the population at large. AB - An emerging challenge facing those who are concerned about the efficacy of public health programs is to understand how information from the DNA revolution might be used to improve our ability to predict the initiation, progression and severity of a common disease having a complex multifactorial etiology. In the course of research to evaluate the role of information about DNA, combinations of genome types and environmental exposures that predispose to disease will be identified. Such information is expected to be useful in efforts to identify individuals and families at higher risk of disease and to predict their responses to a proposed therapy. This paper begins with a discussion of the features of a realistic biological model for the study of a common multifactorial disease. We present evidence for the complexity in the relationship between genome type variation and variation in risk of coronary artery disease (CAD) and review the preliminary results of our studies to determine whether information about genome type variation can improve our ability to predict the distribution of CAD among individuals in the population at large. Such studies make it apparent that new analytical strategies are necessary to deal with the plethora of genome type information available for the evaluation of risk of a common disease like CAD. This shift in the research paradigm will build upon new strategies to understand the organization of natural systems that are coming from outside the mainstream of genetic research. PMID- 7988079 TI - Confounding results of Lp(a) lipoprotein measurements with some test kits. AB - A small number of recent studies have reportedly failed to detect the well established association between a high Lp(a) lipoprotein level and coronary heart disease (CHD). This has made some workers question the importance of a high Lp(a) lipoprotein level as a CHD risk factor. However, serious problems with some of the commercially available test kits, inadequate test techniques or failure to consider the lability of the Lp(a) lipoprotein particle are more plausible explanations of the confounding results. The problems with some of the commercially available test kits include lack of standardization and validation; risk of cross-reactivity with plasminogen or other serum proteins; failure to consider potential problems when measuring samples with varying length of the Lp(a) polypeptide chain (i.e. failure to cope with the isoform variation); non divulgence of contents of test reagents; and pretreatments of samples that drastically change the Lp(a) lipoprotein particles from their native state. Any test system should be validated at the scientific level before it is assumed to provide correct measurements of Lp(a) lipoprotein level in serum. New test kits should be safely anchored in validation in one of the research laboratories active in the area, before they are put on the market. As new batches are produced, the quality of every new batch of test kits should be monitored on a long-term basis in collaboration with a research laboratory. PMID- 7988081 TI - Genetic and environmental influences on LDL subclass phenotypes. AB - There is accumulating evidence that subclasses of low-density lipoproteins (LDL) are important in atherosclerosis. Several case-control studies have demonstrated that a predominance of small, dense LDL (LDL subclass phenotype B) is associated with increased risk of coronary heart disease (CHD). Phenotype B is also consistently characterized by an atherogenic lipoprotein phenotype, including increased levels of plasma triglyceride and decreased high-density lipoprotein cholesterol. Family studies and genetic linkage studies demonstrate that LDL subclasses are influenced by a single major gene effect, although this locus (or loci) remain to be definitively mapped. Twin studies confirm the presence of genetic effects, but also show that non-genetic influences are important. Hypolipidemic drugs, beta-blockers, diet and exercise, in particular, appear to influence the expression of LDL subclass phenotypes. This combination of genetic and environmental influences may provide opportunities to develop targeted intervention strategies to reduce CHD risk among genetically susceptible individuals. PMID- 7988082 TI - From Ag phenotyping to molecular genetics: apolipoprotein B, serum lipid levels and coronary artery disease in Finland. PMID- 7988083 TI - The XbaI polymorphism at the apolipoprotein B locus and risk of atherosclerotic disease. PMID- 7988084 TI - Evidence for single gene contributions to hypertension and lipid disturbances: definition, genetics, and clinical significance. AB - Several large family studies are reviewed to identify results suggesting single gene traits contributing to the occurrence of hypertension in humans. Segregation analysis in families has suggested major gene effects for several highly heritable traits associated with hypertension. These include recessively segregating high sodium-lithium countertransport (major gene H2 = 34%), additively segregating low urinary kallikrein excretion (major gene H2 = 51%), and recessively segregating hyperinsulinemia (major gene H2 = 33%). In some families, hypertension and metabolic abnormalities (dyslipidemia, hyperinsulinemia, and obesity) seem to be related to several candidate genes studied but not conclusively proven (LPL deficiency mutations, dense LDL subfractions, or NIDDM with hyperinsulinemia). More recently, DNA markers have identified genes promoting hypertension. Glucocorticoid-remediable aldosteronism (GRA) promotes a rare but unusual form of hypertension that is unresponsive to ordinary medications but very responsive to glucocorticoid medications. GRA has been found in hypertensive persons with a specific mutation of the 11 beta hydroxylase gene on chromosome 8q21. Many persons with essential hypertension carry a common "susceptibility gene" at the angiotensinogen locus (chromosome 1q4) identified using linkage studies in siblings, association studies, and in studies of preeclampsia and hypertension in pregnant women. These first two well established genetic loci promoting human hypertension represent two ends of a broad spectrum. The rare "determinant" gene for GRA by itself seems to produce severe hypertension and early strokes. The angiotensinogen (AGT) "susceptibility" gene is very common (30% of Utah Caucasians) and seems to predispose to hypertension but probably requires other genetic and environmental influences to be fully expressed.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7988085 TI - Genetic markers in hypercholesterolemic and normocholesterolemic Czech children. AB - The genetic background of polygenic hypercholesterolemia was studied in hypercholesterolemic children consuming a diet identical to control individuals with low cholesterol concentrations. Significantly higher frequencies of "disadvantage" alleles, usually combined with a higher LDL cholesterol, were found in hypercholesterolemic individuals when polymorphisms in apolipoprotein E, apolipoprotein B--XbaI and LDL receptor--PvuII were studied. PMID- 7988086 TI - Mice transgenic for the human LCAT gene. PMID- 7988087 TI - The angiotensin-converting enzyme (ACE) genetic polymorphism: its relationship with plasma ACE level and myocardial infarction. AB - The angiotensin-converting enzyme (ACE) is a key factor in the production of angiotensin II and in the degradation of bradykinin, two important peptides involved in vascular physiology. Plasma and cellular ACE levels in humans are influenced by an insertion (I)/deletion (D) polymorphism of the ACE gene, the ACE I/D polymorphism. The D allele has a frequency of approximately 0.53 in Caucasian populations and is codominantly associated with higher levels of ACE. We have studied this polymorphism in a large multicenter case-control study (the ECTIM study) and found that the D allele was associated with a parental history of fatal myocardial infarction (MI) in the controls and was more frequent in male patients with MI than in controls. This case-control difference was compatible with a codominant effect of allele D on the risk of MI with relative risks of 1.57 for DD vs II and 1.26 for ID vs II (test for trend p < 0.003). In subjects at low risk of MI (plasma ApoB < 1.25 g/l and body mass index < 26 kg/m2), the relative risk of DD vs ID + II was 2.7 (p < 0.0005). The results were very homogeneous in the four populations included in the study. In a family study, using linkage-segregation analysis, we have shown that the ACE I/D polymorphism is a marker for an unknown functional polymorphism (ACE S/s) which appears to be a new independent risk factor for MI. PMID- 7988088 TI - Limb girdle muscular dystrophy: reappraisal of a rejected entity. AB - The term limb girdle muscular dystrophy (LGMD) has been introduced to delineate a distinct form of muscular dystrophy with predominantly proximal upper and lower extremity weakness. Families with evidence of both autosomal recessive and autosomal dominant modes of inheritance have been described. The recognition of other disorders presenting with weakness in a limb girdle distribution, such as the spinal muscular atrophies, dystrophinopathies, inflammatory and metabolic myopathies, casted doubt on the existence of LGMD as a separate entity. Recent linkage studies showing association between various forms of LGMD and loci on chromosome 15, 13 and 5 respectively, and the demonstration of 50K dystrophin associated glycoprotein deficiency in some cases of LGMD, strongly support the notion that limb girdle muscular dystrophy constitutes a separate group of phenotypically and genotypically distinct disorders. Further investigations are necessary to recognize the different subtypes of this disease and to identify the underlying mutations. PMID- 7988089 TI - Silent infarction on a second CT scan in 91 patients without manifest stroke in the Dutch TIA trial. AB - The frequency of silent infarction is an important issue because it is a marker of vascular disease. We studied the occurrence of silent infarction in a sample of patients from the Dutch TIA trial, in which patients were randomized between 30 and 283 mg of aspirin. A total of 91 patients with TIA or non-disabling ischemic stroke and who did not suffer a stroke during a period of one to four years (mean 32 months) underwent CT scanning both on entry and at the end of the study. A cardiac source of embolism was an exclusion criterion for the trial. We found only one patient with a possibly silent infarction; in four patients a previously detected symptomatic infarct on CT was no longer visible. The rarity of silent infarction in this study may have several explanations; (1) the relatively short period of follow-up, (2) the selection of patients (no cardiac source of embolism), (3) the clinical monitoring at four monthly intervals aimed at detection of focal ischemia, (4) the use of aspirin. Given these circumstances, silent infarction is an infrequent problem. PMID- 7988090 TI - Idiopathic spasmodic torticollis: a survey of the clinical syndromes and patients' experiences. AB - We evaluated the medical and psychosocial experiences of 59 patients with idiopathic spasmodic torticollis (ST) by means of a structured questionnaire. The results generally corresponded with those of other studies in the literature. Diagnosis is delayed in many patients, and ST negatively influences the patients' social lives. Because drug treatment and physiotherapy are only of sufficient value in a minority, most patients seek benefit from numerous other therapies, none of which has been shown to improve ST. PMID- 7988092 TI - Long-term outcome of surgically treated unruptured cerebral aneurysms. AB - We report the surgical morbidity and mortality and the results of statistical analysis based on the long-term outcome (average 50.1 months) of 69 patients with unruptured cerebral aneurysms. These patients harbored a total of 76 unruptured cerebral aneurysms, 72 larger than 3 mm in diameter. All the latter were surgically treated. There was no operative mortality. Operative morbidity occurred in 5 patients (7.2%), including hemiplegia in 2 from obliteration of perforator vessels, transient memory impairment in 2 due to brain retraction, and transient oculomotor nerve palsy in 1 patient resulting from an unknown etiology. During the observation period, 53 patients (76.8%) had a good or fair outcome, 11 (15.9%) had a poor outcome, and 5 (7.3%) died from causes unrelated to the aneurysms, such as pneumonia, gastrointestinal bleeding, and heart failure. The 5 year survival rate was 94%. Statistical analysis of the long-term outcome of all patients showed no significantly important factor influencing long-term morbidity. Prophylactic surgery of aneurysm is recommended for low-risk patients who may develop eventual rupture of an aneurysm, but perforator vessels around the aneurysm should be preserved, clips should be properly placed, and brain retraction should be minimized. PMID- 7988091 TI - Radiation-induced osteosarcomas of the skull: report of two cases and review of the literature. AB - Osteosarcoma of the skull as a second neoplasm after radiation therapy is unusual. This neoplasm generally occurs after doses of over 10 Gy. CT, MRI and biopsy are the main diagnostic procedures for this lesion. We report two other cases of osteosarcomas of the skull and review the pertinent literature. PMID- 7988093 TI - Intravascular lymphomatosis of the CNS: clinicopathologic study and search for expression of oncoproteins and Epstein-Barr virus. AB - Five cases of intravascular lymphomatosis (IVL) are reported. Diffuse or focal cerebral signs suggestive of vascular disease occurred in four cases, but case 5 presented with symptoms similar to Creutzfeld-Jakob disease. Clinical course ranged from two to eight months and diagnosis was made in all cases by autopsy. Neoplastic lymphoid cells mainly lodged in lumina of small vessels in many organs, but infarction was confined to the CNS. Some extravascular tumor cells were regularly seen. All cases corresponded to high-grade Non-Hodgkin lymphomas of B-cell type and displayed high proliferation indices. Different from findings in primary cerebral and nodal lymphomas, neither p53 nor bcl-2 oncoproteins were detectable. Absence of EBV genome and EBV latent membrane protein from IVL was demonstrated for the first time. PMID- 7988094 TI - Familial hemiplegic migraine in The Netherlands. Dutch Migraine Genetics Research Group. AB - In this article we describe two Dutch families with familial hemiplegic migraine (FHM). In one family FHM co-segregated with cerebellar ataxia. We discuss the relevance of the genetics of FHM for the research into the genetics of 'normal' migraine with or without aura. PMID- 7988095 TI - Latex agglutination test negative cryptococcal meningitis in an immuno-competent individual: a case report. AB - We report a case with progressive mental deterioration and persistent low grade fever, who was diagnosed to have cryptococcal meningitis. This case is unique in that the cryptococcal latex agglutination antigen test was consecutively negative. The diagnosis was made by sequential CSF culture. PMID- 7988096 TI - Anosodiaphoria for dressing apraxia: contributory factor to dressing apraxia. AB - We report 2 patients with bilateral dressing apraxia. One patient had prominent bilateral dressing apraxia without severe constructional apraxia together with anosodiaphoria for dressing apraxia. The other patient had mild dressing apraxia with severe constructional apraxia and was aware of her disabilities. This dissociation implies that anosodiaphoria for dressing apraxia is an important factor in the severity of bilateral dressing apraxia. This also explains why automatic acts in dressing are more severely affected than when patients are asked to put clothing on in dressing examination. PMID- 7988097 TI - Home EEG and video monitoring in epilepsy: first experiences. AB - In an out-patient epilepsy clinic methods were developed for mobile epilepsy diagnosis and treatment. One of the diagnostic facilities is long-term EEG/video monitoring at home. Method and first results are presented together with a case report of an 8-year-old boy with persistent seizures. PMID- 7988098 TI - Critical illness polyneuromyopathy. PMID- 7988099 TI - Therapeutic drug monitoring and patient outcome. A review of the issues. PMID- 7988100 TI - Clinical pharmacokinetics of fluvoxamine. AB - Fluvoxamine is a selective inhibitor of serotonin reuptake that is widely used in the management of depression. Following oral administration, the drug is absorbed efficiently from the gastrointestinal tract. Peak plasma concentrations are usually observed within 2 to 8 hours postdose for capsules and film-coated tablets and within 4 to 12 hours for enteric-coated tablets. Despite complete absorption, oral bioavailability may be incomplete probably because of first-pass metabolism. Approximately 77% of fluvoxamine is plasma protein bound. Only negligible amounts of fluvoxamine are excreted unchanged in urine. The drug is extensively biotransformed, mostly by oxidation, and at least 11 different metabolites have been detected in human urine. None of the metabolites is known to possess significant pharmacological activity. Following administration of single doses, fluvoxamine shows a biphasic elimination with a mean terminal elimination half-life of about 15 to 20 hours. Steady-state plasma fluvoxamine concentrations are achieved 5 to 10 days after initiation of therapy and are 30 to 50% higher than those predicted from single-dose data. Preliminary data also suggest that plasma drug concentrations may increase nonlinearly with increasing daily dosage. The relationship between plasma fluvoxamine concentration and clinical response has not been clearly defined. Fluvoxamine pharmacokinetics are substantially unaltered in the elderly, whereas higher plasma drug concentrations (relative to dose) are observed in patients with alcoholic cirrhosis of the liver. Fluvoxamine inhibits oxidative drug metabolising enzymes and, therefore, causes a number of clinically significant drug interactions. Drugs whose metabolic elimination is impaired by fluvoxamine include tricyclic antidepressants, alprazolam, bromazepam, diazepam, theophylline, phenazone (antipyrine), propranolol, warfarin, methadone and carbamazepine. PMID- 7988101 TI - Clinical pharmacokinetic advantages of new drug delivery methods for the treatment of liver tumours. AB - Response rates following systemic chemotherapy for hepatic tumours are disappointing. The drugs used have a narrow therapeutic ratio, which limit the scope for dose escalation of these potentially toxic agents. Therefore, alternative delivery methods that optimise the efficacy of currently available cytotoxic agents have been explored. Several novel approaches have attempted to 'target' treatment so that it reaches the tumour whilst minimising systemic exposure. There is some evidence to suggest that certain agents, including monoclonal antibodies and liposomes, selectively lodge in tumours following intravenous administration. Alternatively, the route of administration may be modified to enhance targeting of the administered drug. Delivery via the hepatic arterial, portal venous, and peritoneal routes as well as drug delivery via direct implantation may provide certain pharmacokinetic advantages. Infusion rates may be adjusted to optimise the pharmacokinetic profile. Chemoembolisation with microspheres, microcapsules or macromolecules might enhance targeting further. Variations in particle characteristics or by modifying hepatic arterial blood flow with vasoactive substances may be used to further refine this technique. The ultimate 'magic bullet', which allows total delivery of treatment to malignant cells whilst eliminating exposure of healthy tissues to these toxic agents, has not been developed as yet. However, currently available techniques allow considerable dose escalation that, whilst not providing a significant survival advantage, certainly improves response rates. PMID- 7988102 TI - Role of patient compliance in clinical pharmacokinetics. A review of recent research. AB - Until 1986 to 1987, the estimation of patient compliance with prescribed drug regimens in ambulatory care relied on methods that were biased either by their subjectivity or by the improvement in compliance that commonly occurs during the day or two prior to a scheduled examination, so called 'white-coat compliance'. In 1986 to 1987, 2 objective methods were developed: electronic monitoring and low-dose, slow-turnover chemical markers (digoxin or phenobarbital [phenobarbitone]) incorporated into dosage forms. While neither method is without limitations, both have enabled major advances in the understanding of patients' compliance with dosage regimens and, thus, the spectrum of drug exposure in ambulatory care. The new methods have also triggered not only a revival of interest in patient compliance and its determinants, but also new statistical approaches to interpreting the clinical correlates of widely variable drug administration, and thus drug exposure, in drug trials. The marker methods prove dose ingestion during the 3 to 7 days prior to blood sampling, but do not reveal the timing of doses. The electronic monitoring methods, i.e. time and date stamping microcircuitry incorporated into drug packages, provide a continuous record of timing of presumptive doses throughout periods of many months, but do not prove dose ingestion. The electronic record has been judged robust enough to detect certain types of investigator fraud, and to support modelling projections of the complete time course of the plasma drug concentration during a trial. Both marker and electronic methods show that the predominant errors are those of omission, i.e. delays or omissions of scheduled doses. Patient interviews, diaries, and counts of returned, untaken doses have been shown by both marker and electronic monitoring methods to consistently and substantially to overestimate compliance. Monitoring of plasma drug concentrations also overestimates compliance, because white-coat compliance is prevalent, and the pharmacokinetic turnover of most drugs is rapid enough that measured concentrations of drug in plasma reflect only drug administration during the period of white-coat compliance. Thus, compliance is a great deal poorer in clinical trials than has been revealed by the older methods. The long-standing underestimation of poor compliance in drug trials has many implications for the interpretation of drug trials, for optimal dose estimation, for the interpretation of failed drug therapy, and for accurate labelling of prescription drugs. PMID- 7988104 TI - Architectures for numerical cognition. AB - Current theories of numerical cognition differ in assumptions about the componential architecture of number processing and about the extent of notation specific processes. To investigate these issues, 64 adult subjects were tested on simple addition and multiplication problems presented in Arabic digit or English number-word format. Overall, response times and error rates were much higher with the word format, but more importantly, presentation format interacted with arithmetic operation and problem size. Operation errors (2 + 4 = 8), operand naming errors (2 + 8 = 8), and operand-intrusion errors (9 x 6 = 36) were each characterized by a different format x operation interaction, and analysis of inter-trial error priming showed selective interference from preceding trials as a function of number format. These types of format-specific retrieval interference and operation-specific effects of format are problematic for models that hypothesize notation-independent memory processes for arithmetic. Furthermore, analyses of operand-naming errors, operand-intrusion errors, and other operand-priming effects, revealed strong interactions of number reading and number-fact retrieval processes; processes that are typically posited to be functionally independent. The results suggest a complex encoding architecture that incorporates notation-dependent activation of addition and multiplication facts, as well as interpenetration of number reading and number-fact retrieval processes. PMID- 7988105 TI - Children's theory of mind: Fodor's heuristics examined. AB - The study reported in this manuscript examined Fodor's (1992) argument that standard false belief tasks used in developmental research seriously underestimate young children's understanding of false belief. The problem of these tasks according to Fodor is that always a unique, actual state of affairs (e.g., chocolate is now in cupboard B) is contrasted with a believed state of affairs (e.g., chocolate is still in cupboard A). Fodor argued that this uniqueness feature may be critical because young children with limited computational resources have to trade reliability of behavioral prediction for computational simplicity and, therefore, may rely on simple heuristics such as "Predict that the agent will act in a way that will satisfy his desires". In the standard false belief task such a heuristic will result in a unique, but incorrect (reality-based) prediction. Fodor's expectation is that when young children are not misled into applying such heuristics by the possibility of unique, reality-based prediction, then their true competence for belief-based reasoning will become evident. The present study contrasted for two different belief tasks a traditional unique version with a non-unique version, but found no support for Fodor's expectation as both 3- and 4-year-old children did not improve in the non-unique version. PMID- 7988106 TI - Categories of social relationship. AB - The study of social relationships lies at the heart of the social sciences, but our understanding of the cognitive structures that support them has received little attention. This paper develops an account of the form and content of these structures, arguing that social relationships are represented by a small number of categories, rather than by dimensions as proposed by others. Taxometric analyses demonstrated that categories proposed by Fiske (1991) are truly discrete, controverting dimensional representation and one possible form of prototype structure. The categories appear to combine in the specification of actually existing social relationships, and are more informative, or "basic", then colloquial relationship categories. PMID- 7988107 TI - The role of standards and safety-critical software in clinical practice. PMID- 7988108 TI - Approaching safe and secure health information systems in Europe. AB - Information systems in health care are being utilised in more and more demanding and more clinical situations where security and safety issues become more significant. These issues are explored within the context of the UK National Health Service and the corresponding activities within the European Union. PMID- 7988109 TI - Information management systems for intensive care. AB - On-going work relating to the development of advanced information management systems for intensive care is described. The objective of this paper is to outline the complex issues that need to be addressed when developing such systems. This work is in part sponsored by the Commission of the European Communities under the AIM TANIT project, and an overview of its approach is given. Data protection, security and confidentiality aspects are emphasised, together with the need to balance data availability with the need for security. PMID- 7988110 TI - Safety assessment of data management in a clinical laboratory. AB - This paper briefly reviews work undertaken within the DTI-sponsored MORSE project. The Clinical Biochemistry Department of the West Middlesex University Hospital, one of the five project partners, provides clinical and laboratory services to a wide range of users. The Laboratory Information Management System used within the department has been developed using a range of commercially available hardware and software together with software that has been designed and developed within the laboratory. This paper reports on the first stages of safety analysis of the overall operations in the laboratory. This is a pre-cursor to the systematic re-development of the information system in the light of the findings of the safety analysis. PMID- 7988111 TI - Hazard analysis of a computer based medical diagnostic system. AB - Medical screening of sectors of the population is now a routine and vital part of health care: an example is cervical smear testing. There is currently significant interest in the possible introduction of semi-automated microscopy systems for cervical cytology and one such experimental system is now undergoing laboratory trials. A collaborative project has been set up to demonstrate the benefits and constraints that arise from applying safety-critical methods developed in other domains to such a diagnostic system. We have carried out a system hazard analysis, successfully using the HAZOP technique adapted from the petrochemical industry. PMID- 7988112 TI - Safety-critical software and current standards initiatives. AB - This paper sets out to examine the role of standards in the development of safety critical software. It starts with a brief discussion on the nature and role of standards and then moves on to identify some of the standards making bodies. Safety-critical software is next discussed and the problems of software safety are contrasted with those of traditional electromechanical devices. There then follows a review of some of the current initiatives to produce standards addressing the development of safety-critical systems containing software. Two standards are then examined in detail to provide an insight into what requirements are placed on the developers of safety-critical software. Lastly, mention is made of some weaknesses that are inherent in today's standards, and some of the efforts that are being made to address these problems are discussed. PMID- 7988113 TI - An overview of software assessment. AB - Many engineering systems, especially those required to be particularly dependable, traditionally undergo inspections and assessments of safeness and fitness for purpose. Often some form of 'certificate' is provided by the assessment authority. To an increasing degree these systems are beginning to contain software components. The question naturally arises: how can the software component be assessed? This paper explores the feasibility and limitations of software assessment and the link between the process of developing the software and the quality of the resulting software product. PMID- 7988114 TI - A computerised cancer registry data and validation system in India--its implications for developing countries. AB - The cancer registration system in India, and an appropriate computer program to validate the cancer patient data it generates, are described, with the resource inputs, and outputs of research, training, awareness creation and cancer control, in the context of local health care systems. Computer packages already available mostly address the type of data obtainable from western health care systems. The same factors that limit health care systems in India, and probably most other developing countries--inadequate health care facilities, skeletal medical records systems, meagre and unavailable vital statistics, few trained staff, funding and computer facilities--also limit the data sent to the National Cancer Registry Programme. The computer program we developed checks for the reliability and validity of various cancer diagnostic, spread, therapeutic and outcome variables. The program is in HIBASIC for a CPM operating system with a minimum of 64 kB memory, adaptable to MS-DOS systems, population-based cancer registry data, and perhaps to other types of chronic disease registries, with relevant modifications. Since reliable cancer registry data are needed for effective cancer control measures, this program may help in such efforts in developing countries. PMID- 7988115 TI - A knowledge acquisition tool in analytical pathology based on multi-media relational database. AB - The need for a knowledge based expert system for efficient decision making in the field of pathology has been well accepted. To build the knowledge-base for such an expert system is a painstaking task. This work is an attempt to provide the pathologists a powerful and user-friendly tool that will help them in the process of building the knowledge-base for medical diagnosis by closely looking at the specimen images and their extracted feature values. The tool is based on multi media relational database and software like VAX Rally (4GL), ILIAD and SAS to provide a wide-range comparative study between feature data and image data; and also their statistical analysis. PMID- 7988103 TI - Assessment of liver metabolic function. Clinical implications. AB - Inter- and intraindividual variability in pharmacokinetics of most drugs is largely determined by variable liver function as described by parameters of hepatic blood flow and metabolic capacity. These parameters may be altered as a result of disease affecting the liver, genetic differences in metabolising enzymes, and various types of drug interactions, including enzyme induction, enzyme inhibition or down-regulation. With the now known large number of drug metabolising enzymes, their differential substrate specificity, and their differential induction or inhibition, each test substance of liver function should be used as a probe for its specific metabolising enzyme. Thus, the concept of model test-substances providing general information about liver function has severe limitations. To test the metabolic activity of several enzymes, either several test substances may be given (cocktail approach) or several metabolites of a single test substance may be analysed (metabolic fingerprint approach). The enzyme-specific analysis of liver function results in a preference for analysis of the metabolites rather than analysis of the clearance of the parent test substance. There are specific methods to quantify the activity of cytochrome P450 enzymes such as CYP1A2, CYP2C9, CYP2C19MEPH, CYP2D6, CYP2E1, and CYP3A, and phase II enzymes, such as glutathione S-transferases, glucuronyl-transferases or N acetyltransferases, in vivo. Interactions based on competitive or noncompetitive inhibition should be analysed specifically for the cytochrome P450 enzyme involved. At least 5 different types of cytochrome P450 enzyme induction may result in major variability of hepatic function; this may be quantified by biochemical parameters, clearance methods, or highly enzyme-specific methods such as Western blot analysis or molecular biological techniques such as mRNA quantification in blood and tissues. Therapeutic drug monitoring is already implicitly used for quantification of the enzyme activities relevant for a specific drug. Selective impairment of hepatic enzymes due to gene mutations may have an effect on the pharmacokinetics of certain drugs similar to that caused by cirrhosis. Assessment of this heritable source of variability in liver function is possible by in vivo or ex vivo enzymological methods. For genetically polymorphic enzymes and carrier proteins involved in drug disposition, molecular genetic methods using a patient's blood sample may be used for classification of the individual into: (i) the impaired or poor metaboliser (homozygous deficient); (ii) the extensive (homozygous active) metaboliser group; and (iii) the moderately extensive metaboliser (heterozygous) group. For hepatic blood flow determinations, galactose or sorbitol given at relatively low doses may be much better indicators than the indocyanine green.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 7988116 TI - A method for co-registering three-dimensional multi-modality brain images. AB - A method has been developed for co-registering three-dimensional multi-modality images of the human brain. The interactive program allows users to specify the interhemispheric fissure plane in three dimensions by identifying the endpoints of the centerline within transaxial slices. Translations and rotations within transaxial and coronal planes are determined to align the interhemispheric fissure planes of the two image sets to be co-registered. After reslicing the two partially co-registered image volumes, the intercommissural lines are detected by using three internal landmarks. A transformation including translation and rotation in the sagittal plane finally co-registers the two image sets in three dimensional space. Single photon emission computed tomography (SPECT) images and magnetic resonance (MR) images have been used to validate the method for co registering three-dimensional functional and anatomic brain images. This new co registration method requires neither special head positioning procedures nor external fiducial markers, thereby making it appropriate for the routine clinical practice. PMID- 7988117 TI - Shading correction and calibration in bacterial fluorescence measurement by image processing system. AB - An image processing system with applications in bacterial (immuno-)fluorescence measurement has been developed. To reach quantitative results, correction for non uniformities in system sensitivity, both as a function of time (calibration for drifts) and as a function of image coordinates (shading correction), is essential. Both problems can be handled simultaneously by acquiring images of a uniformly fluorescent, solid standard as a reference image. To measure bacterial fluorescence, the average fluorescence intensity of isolated areas of interest (the bacteria) is computed, and corrected using the reference images. Two shading correction methods are theoretically and experimentally compared: direct averaging in the corrected image, and (weighted and unweighted) averaging using the raw image and a separate shading image to determine the weights and correct for shading during the averaging. The latter method proved computationally 3.5 6.5 times faster on average and reduced propagation of truncation errors during computation, resulting in 40% less noise, for 8-bits/pixel images. PMID- 7988118 TI - Analysing nuclear shape as a function of relative spatial position in the femoral insertion of the medial collateral ligament. AB - Quantification of biological structure by morphometry facilitates the correlation of structure to biological function. To test a hypothesis concerning the correlation of a gradient in cell and nuclear shape and a corresponding gradient in mechanical stress within a ligament insertion into bone, a computerized approach was developed for quantifying mean nuclear shape as a function of position within this insertion. Three femoral insertions of the medial collateral ligament of the rabbit were prepared for histology. Commercially available software was used to measure nuclear perimeter and area by video-based planimetry on microscopic images, then custom software was used to define an overlying mesh of polygons on each insertion, to normalize the geometry of the insertion, and to calculate the mean nuclear roundness (a function of area and perimeter) for each polygon in the mesh. This approach allows the comparison of mean nuclear roundness of different polygons and among different animals that would be extremely difficult to do manually. In addition, these morphometry results can be used to correlate with functional data. PMID- 7988120 TI - Computer simulation of propagated activation in different types of left ventricular enlargement. AB - An increase of the left ventricular mass does not always have an unambiguous effect on the electro- or vectorcardiographic image of ventricular activation. To analyse this phenomenon, three types of left ventricular enlargement were simulated by a computer model of propagated activation in cardiac ventricles. These were obtained from the reference (normal) left ventricle by an increase of its wall thickness either centripetally or centrifugally, as well as by increase of the ventricular cavity dimensions (dilatation). Two different degrees of mentioned changes, corresponding to an increase of the value of the respective parameters by 50% or 100% of reference left ventricular wall thickness, were analysed. In the case of a centrifugal increase of left ventricular wall thickness, the magnitude of instantaneous cardiac vectors increased only during the last two-thirds of ventricular activation time. A centripetal increase of the wall thickness resulted in a decrease of the resultant cardiac vector magnitudes during the first half of ventricular activation followed by their slight increase. In dilatation of the left ventricle the cardiac vectors were enhanced during the whole activation time. PMID- 7988119 TI - A statistical analysis system macro for age-standardized incidence rates. AB - The Statistical Analysis System (SAS) is a commercial software system for data analysis. We designed a SAS macro that produces age-specific rates of any given disease directly from the basic patient data on SAS files. The macro conforms to the statistical methods of the World Health Organization's MONICA project, which is a multinational project for MONItoring of trends and determinants in CArdiovascular disease. The data of the Coronary Register of the City of Turku, Finland, was used to test this macro. The data consists of both men and women between the ages of 35 and 64 years. Acute coronary events leading to hospitalization and acute coronary death events outside hospital have been registered since 1972. For age-standardization Segi's world population was used as the standard. The weights were then calculated for five consecutive years. Individual weights related to the population size of the reporting unit and the standard population were calculated for each subject in the population using the population size of the reporting unit and the standard population. This yielded the age-standardized rates of the acute myocardial infarction and the corresponding standard deviations. The macro permits standardization of the incidence rates of any disease. It will present the required figures instantly. PMID- 7988121 TI - Computer program for connection and data management of an automated coagulation system: the KC 10. AB - In Europe, the KC 10, manufactured by Amelung Germany, is one of the instruments most commonly found in coagulation laboratories. For facilitating the work of technical validation, we wrote a software adapted to any IBM or compatible PC running under MS-DOS, to manage the analyser performance. Data are automatically collected via the BCD interface from the analyser or keyed in for the other techniques. The software deals with 64 different analyses entirely 'user defined'. An 'electronic worksheet' presents the results, by page of ten patients. This enables the laboratory technician to assess the coherence of the various data and to perform verifications or complementary tests if necessary. As an option, a blinking asterisk can signal all results outside predetermined range. By moving the cursor through the table, a test result can be deleted, modified or added. A function displays the patient's previous files in a window because the data are recorded in long-term archives at the end of the day. This long-term recording allows a search of previous files to decide additional tests if the patient is unknown. A daily archive function classifies and prints the whole day's work in alphabetical order. A protocol of communication allows connection to a mainframe Bayer-Technicon computer. This program and the user's manual are free, available on request from address above. PMID- 7988122 TI - MIAMOD: a computer package to estimate chronic disease morbidity using mortality and survival data. AB - The MIAMOD package is for use in epidemiological analysis of chronic degenerative diseases. The package has been designed to use survival and mortality data supplied by the user, to estimate incidence and prevalence rates, to forecast future mortality and morbidity levels and to provide life tables. Estimates are derived by modelling incidence as an age-period-cohort function and by the equations relating specific cause mortality and prevalence to incidence and survival. The model parameters are evaluated by fitting mortality data by means of a weighted non-linear regression model. Numerical and statistical methods used to solve the regression and to compute standard errors, projections, and life tables are discussed. The program is written in standard FORTRAN 77 and runs on a mainframe computer. The different program units are illustrated together with the principal implementation options. An example of application is provided to show a typical output pattern. PMID- 7988123 TI - Are dopamine and/or dobutamine renoprotective in intensive care unit patients? PMID- 7988124 TI - Cocaine plus ethanol is more cardiotoxic than cocaine or ethanol alone. AB - OBJECTIVES: The purpose of this study was to determine the hemodynamic effects of recreational/toxic doses of ethanol, or cocaine, or ethanol followed by cocaine. DESIGN: Prospective, randomized study. SETTING: University research laboratory. SUBJECTS: Eighteen healthy, adult mongrel dogs. INTERVENTIONS: Dogs were randomized to receive ethanol (1 g/kg iv) over 20 mins and a 10-mL bolus of 0.9% sodium chloride, or 5% dextrose in water, over 20 mins, and then a cocaine bolus (7.5 mg/kg), or ethanol (1 g/kg iv), over 20 mins, and then a cocaine bolus (7.5 mg/kg). MEASUREMENTS AND MAIN RESULTS: Arterial, left ventricular, and pulmonary arterial pressures, mixed venous blood oxygen saturation, and heart rate (HR) were continuously recorded in each dog. The maximal rate of left ventricular pressure increase (dP/dtmax) and decrease (dP/dtmin), stroke volume, HR, pulmonary artery occlusion pressure (PAOP), and plasma concentrations of ethanol and cocaine were measured at baseline, after ethanol or placebo infusions, and then after a cocaine or placebo bolus at specific time intervals over a 5-hr study period. The plasma ethanol concentration increased to 160 +/- 8 mg/dL at 30 mins after the start of the infusion, and then decreased to 30 +/- 8 mg/dL at 180 mins. The plasma cocaine concentration increased to 4587 +/- 383 ng/mL within 2 mins of the bolus injection, and then decreased and approached the baseline at 240 mins. Immediately after injection, ethanol plus cocaine synergistically decreased dP/dtmax by 70% and dP/dtmin by 81% (both p < .001). In addition, immediately after injection, ethanol plus cocaine maximally decreased the stroke volume by 34% (p < .05) and maximally increased the HR by 89% and PAOP by 127% (both p < .002). The dP/dtmax and the stroke volume remained decreased by 15% to 20% for 5 hrs (p < .05). Cocaine alone, immediately after injection, maximally decreased dP/dtmax and dP/dtmin by 40% (p < .02), and caused a 26% decrease in stroke volume (p = .05), a 48% increase in HR (p < .02), and a 75% increase in PAOP. The decrease in dP/dtmax persisted for approximately 60 to 90 mins. Ethanol alone produced transient 6% to 13% decreases in dP/dtmax, dP/dtmin, and stroke volume (NS) and small (9%) increases in the HR (NS) during the first hour after injection. CONCLUSION: Cocaine combined with ethanol produces a significant synergistic depression of ventricular contraction and relaxation that substantially exceeds the arithmetic sum of the depressive effects of either cocaine or ethanol alone. PMID- 7988126 TI - Is continuous cardiac output measurement using thermodilution reliable in the critically ill patient? AB - OBJECTIVE: Evaluation of continuous cardiac output monitoring based on the thermodilution technique in the critically ill. DESIGN: Prospective clinical investigation. SETTING: A surgical intensive care unit of a university hospital. PATIENTS: Thirty-five critically ill patients (trauma and/or sepsis patients), who needed pulmonary artery catheterization. The patients were prospectively studied according to the following groups: a) patients with a heart rate of > 120 beats/min; b) those patients with a cardiac output of > 10 L/min; c) patients with a cardiac output of < 4.5 L/min; d) patients with a rectal temperature of > 39.0 degrees C; and e) patients with a pulmonary artery catheter inserted for > 4 days. INTERVENTIONS: Therapies were carried out according to modern intensive care medicine protocols by physicians who were not involved in the study. MEASUREMENTS: Cardiac output was monitored continuously using a new, modified pulmonary artery catheter. This catheter has a heating filament by which energy is transmitted to the circulating blood (modified thermodilution technique). A bedside microprocessor calculated cardiac output using a new algorithm. Standard bolus thermodilution technique (10 mL of ice-cold saline solution) was used to compare the continuous cardiac output measurement with the intermittent bolus cardiac output measurement. MAIN RESULTS: A total of 404 pairs of intermittent (bolus) cardiac output and continuous cardiac output measurements were obtained from the 35 patients. The bias (mean difference between bolus cardiac output measurement and continuous cardiac output measurement) of all measurements was 0.03 +/- 0.52 L/min and the 95% confidence limit (mean difference +/- 2 SD) was 1.01/1.06 L/min. Also, continuous cardiac output measurement agreed closely with bolus cardiac output measurement (bias was 0.16 +/- 0.57 L/min in the cardiac output of > 10 L/min group; bias was -0.17 +/- 0.50 L/min for the cardiac output of < 4.5 L/min group). Increased temperature and prolonged length of stay did not influence the agreement of continuous cardiac output measurement with bolus cardiac output measurement (bias was 0.09 +/- 0.51 L/min in the > 39 degrees C rectal temperature group). CONCLUSIONS: Continuous monitoring of cardiac output using a modified pulmonary artery catheter with a heated filament has proven to be accurate and precise in the critically ill patient when compared with the "standard" intermittent bolus thermodilution technique. The continuous monitoring technique enhances our armamentarium for more intensive monitoring of these patients under a variety of circumstances. PMID- 7988125 TI - Multicenter trial of a new thoracic electrical bioimpedance device for cardiac output estimation. AB - OBJECTIVE: To evaluate the capacity of a new thoracic electric bioimpedance system to estimate cardiac output compared with the conventional thermodilution method. DESIGN: Prospective, multicenter study. SETTING: A university-run county hospital, a university-run U.S. Veterans Affairs hospital, and a university affiliated U.S. military hospital. PATIENTS: A series of 68 critically ill patients whose conditions required pulmonary artery catheter insertion. MEASUREMENTS AND MAIN RESULTS: A total of 842 simultaneous pairs of cardiac output estimations by conventional thermodilution and a new thoracic electric bioimpedance system that uses an improved signal processing technique based on an all-integer-coefficient filtering technology, using a time-frequency distribution that provides a high signal/noise ratio were evaluated. The r value was .86, r2 = .74, and p < .001 by regression analysis; the mean difference between the two methods relative to their average value was 16.6 +/- 12.9 (SD) %; the precision was 1.4 L/min or 0.8 L/min/m2; the bias was -0.013 L/min. The mean difference between successive pairs of thermodilution measurements was 8.6 +/- 0.6 (SD) %, which was about half the difference between simultaneous pairs of measurement by the two methods. The changes in impedance estimations were close to simultaneously measured changes in thermodilution estimates of cardiac output. CONCLUSIONS: The new bioimpedance system satisfactorily estimated cardiac output as measured by the thermodilution technique. The difference between the two estimations is more than made up for by the continuous noninvasive capability of the impedance system. PMID- 7988127 TI - Renal support in critically ill patients: low-dose dopamine or low-dose dobutamine? AB - OBJECTIVE: Low-dose dopamine has been used in critically ill patients to minimize renal dysfunction without sufficient data to support its use. The aim of this study was to determine whether low-dose dopamine improves renal function, and whether dobutamine, a nondopaminergic inotrope, improves renal function. DESIGN: Prospective, randomized, double-blind trial. PATIENTS: Twenty-three patients at risk for renal dysfunction were entered into the study. Five patients were later withdrawn. Study data for the remaining 18 patients were: mean age 55 yrs; mean Acute Physiology and Chronic Health Evaluation (APACHE) II score of 18; mean weight 71 kg). The following conditions were present: mechanical ventilation (n = 17 [inverse-ratio ventilation, n = 6]); inotrope administration (n = 11); sepsis (n = 13); and adult respiratory distress syndrome or multiple organ failure syndrome (n = 9). INTERVENTIONS: The study patients were administered dopamine (200 micrograms/min), dobutamine (175 micrograms/min), and placebo (5% dextrose) over 5 hrs each in a randomized order. Ventilator settings, fluid management, and preexisting inotropic support were not altered during the study. MEASUREMENTS AND MAIN RESULTS: Systemic hemodynamic values and indices of renal function (4-hr urine volume, fractional excretion of sodium, and creatinine clearance) were measured during the last 4 hrs of each infusion. Dopamine produced a diuresis (145 +/- 148 mL/hr) compared with placebo (90 +/- 44 mL/hr; p < .01) without a change in creatinine clearance. Conversely, dobutamine caused a significant increase in creatinine clearance (97 +/- 54 mL/min) compared with placebo (79 +/- 38 mL/min; p < .01), without an increase in urine output. CONCLUSIONS: In stable critically ill patients, dopamine acted primarily as a diuretic and did not improve creatinine clearance. Dobutamine improved creatinine clearance without a significant change in urine output. PMID- 7988128 TI - Variability in dobutamine pharmacokinetics in unstable critically ill surgical patients. AB - OBJECTIVE: To delineate the variability in the pharmacokinetics of dobutamine over time in an unstable critically ill adult surgical patient population concurrently receiving therapeutic interventions to optimize oxygen delivery and consumption variables. DESIGN: Prospective study. SETTING: University hospital adult surgical intensive care unit. PATIENTS: Sixteen hemodynamically unstable adults (aged 18 to 84 yrs) requiring dobutamine for inotropic support. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Samples for dobutamine serum concentration determination were collected at selected times during therapy, following at least 30 mins of a constant infusion rate and measured using high performance liquid chromatography. Clearance and changes in clearance were calculated. A first-order pharmacokinetic model was validated by lack of dependence of dose on clearance and an established graphical method. Mean +/- SD infusion rate of dobutamine was 8.2 +/- 5.7 micrograms/kg/min (range 1.7 to 22.3), which resulted in a mean serum concentration of 214 +/- 183 ng/mL (range 15 to 759). The correlation between infusion rate and steady-state dobutamine concentration was r2 = .67. Variability in steady-state dobutamine concentration at various infusion rates was large. Clearance at initial pharmacokinetic analysis averaged 58.4 +/- 33.3 mL/kg/min (range 19 to 120). The percent change in calculated clearance varies from a 72% decrease to an 88% increase, with the greatest variability in clearance occurring during the first 24 hrs of therapy. There was little correlation between initial dobutamine clearance and weight (r2 = .10), net cumulative fluid balance before initiation of dobutamine (r2 < .01), age (r2 = .20), and estimated creatinine clearance (r2 = .09). CONCLUSIONS: Dobutamine pharmacokinetics in adult critically ill patients is best described by a first-order model. Pathophysiologic factors may have an effect on the pharmacokinetics of dobutamine which appears to change over time. Both inter- and intrapatient variability in infusion rate administered and resultant serum concentrations were wide, suggesting that infusion rate should be guided by clinical end points rather than by predetermined values. PMID- 7988129 TI - Influence of pressure- and flow-triggered synchronous intermittent mandatory ventilation on inspiratory muscle work. AB - OBJECTIVE: To determine the effect of pressure- and flow-triggered synchronous intermittent mandatory ventilation on inspiratory muscle work. DESIGN: Consecutive clinical, prospective, randomized trial. SETTING: Medical intensive care unit (ICU) of a U.S. Veterans Affairs Medical Center. PATIENTS: Eight patients recovering from acute respiratory failure of various etiologies. INTERVENTIONS: Assist control, followed by randomized application of pressure- and flow-triggered synchronous intermittent mandatory ventilation at 60%, 40%, 20% of the assist-control rate, and flow-triggered continuous positive airway pressure. A total of eight settings were maintained for 10 mins each. MEASUREMENTS AND MAIN RESULTS: Total work rate (joules/min), inspiratory muscle work (joules/L), and pressure time-product per breath (cm H2O-sec) were measured. During pressure- or flow-triggered synchronous intermittent mandatory ventilation, total work rate increased as the mandatory rate was decreased. The method of ventilator triggering had a significant effect on the total work rate. With pressure-triggered synchronous intermittent mandatory ventilation, the total work rate at 60% of the assist-control rate was similar to that with assist control; whereas with flow-triggered synchronous intermittent mandatory ventilation, this result was achieved at 40% of the assist-control rate. At a machine support level of 20%, total work rate with pressure-triggered synchronous intermittent mandatory ventilation was significantly greater than with flow triggered synchronous intermittent mandatory ventilation. The method of ventilator triggering had no significant effect on the inspiratory muscle work of the mandatory breaths. This finding was in contrast to the effect on inspiratory muscle work of spontaneous breaths. With pressure-triggered synchronous intermittent mandatory ventilation, inspiratory muscle work of the spontaneous breaths was greater than with the flow-triggered at machine support of 40% and 20%. With either pressure- or flow-triggered synchronous intermittent mandatory ventilation, inspiratory muscle work of the mandatory breaths was not significantly different from that of the corresponding spontaneous breaths, except at the lower machine support levels with the pressure-triggered synchronous intermittent mandatory ventilation. Pressure-time product followed a trend similar to that of inspiratory muscle work. CONCLUSIONS: During synchronous intermittent mandatory ventilation, the method of ventilator triggering has a significant effect on the total work rate and inspiratory muscle work of the spontaneous breaths, particularly at lower machine support levels. Conversely, the method of ventilator triggering has no significant effect on inspiratory muscle work of the mandatory breaths. PMID- 7988130 TI - Mechanical ventilators optimized for pediatric use decrease work of breathing and oxygen consumption during pressure-support ventilation. AB - OBJECTIVES: a) To investigate whether the patient work of breathing needed to trigger inspiration is affected by the type of ventilator delivering pressure support ventilation for mechanically ventilated pediatric patients. b) To determine whether changes in oxygen consumption (VO2) trend with changes in work of breathing and would thus be helpful in tracking work of breathing. DESIGN: Prospective study. SETTING: Pediatric intensive care unit at a university hospital. PATIENTS: Nine mechanically ventilated patients (2 to 75 months of age). INTERVENTIONS: While maintaining a constant pressure-support ventilation level, patients were alternately supported with the Siemens Servo 900C, the Bird VIP, and the Newport Wave E200 ventilators in random order. MEASUREMENTS AND MAIN RESULTS: Work of breathing, defined as the integral of the pressure-volume curve corresponding to negative pressure, was calculated with a pulmonary monitoring system. VO2 was measured with a metabolic cart. Patient distress levels were assessed using the COMFORT scale, a behavioral scoring system. Mean values (20 breaths/patient) for measured variables with each ventilator were compared using analysis of variance and Scheffe tests, with p < .05 indicating statistical significance. The lowest VO2 (103 +/- 35 mL/min/m2) and work of breathing (24 +/- 15 g.cm/m2) were achieved with the Bird VIP ventilator and were significantly (p < .05) lower than those values obtained with either the Siemens Servo 900C (VO2 147 +/- 33 mL/min/m2; work of breathing 49 +/- 18 g.cm/m2) or the Newport Wave E200 (VO2 122 +/- 33 mL/min/m2; work of breathing 35 +/- 15 g.cm/m2). Also, the values of work of breathing and VO2 obtained using the Newport Wave E200 were significantly (p < .05) lower than those values obtained using the Servo 900C. No change in behavioral distress occurred when the ventilators were changed. In all patients, there was a clear similarity in the trends of VO2 and work of breathing. CONCLUSIONS: We conclude that VO2 and work of breathing may be reduced significantly using the latest generation of mechanical ventilators optimized for infant and pediatric use. Because work of breathing is less with the Bird VIP than the other two ventilators tested, leading to a corresponding decrease in VO2, we suggest that the Bird VIP better adapts the patient to the ventilator and may facilitate weaning from ventilatory support. We also suggest that changes in VO2 might be helpful in tracking changes in work of breathing. PMID- 7988131 TI - Prospective endoscopic study of stress erosions and ulcers in critically ill adult patients treated with either sucralfate or placebo. AB - OBJECTIVE: To compare the frequency of stress erosions and ulcers in critically ill adult patients treated with either sucralfate or placebo. DESIGN: Prospective, randomized study. SETTING: Intensive care unit in a university hospital. PATIENTS: Twenty-six adult patients. All patients were mechanically ventilated and were at risk of developing stress ulceration. INTERVENTIONS: Patients were randomized to receive either sucralfate (2 g every 8 hrs) (group 1) via the nasogastric tube (flushed with 10 mL of sterile water) or 20 mL of sterile water every 8 hrs (group 2) via the nasogastric tube. MEASUREMENTS AND MAIN RESULTS: At the time of intensive care unit admission, the frequency of stress (acute) erosions (as assessed with the endoscope) was 21.7%. No ulcers were detected. By day 3, the frequency had increased to 37.5% in group 1 and 88.9% in group 2. Mucosal deterioration was more likely in the patients treated with placebo (water) (p < .05). In total, seven patients developed acute ulceration in group 2 compared with only one patient in group 1 (p < .05). The frequency of gastric colonization with aerobic Gram-negative bacilli was 25.6% in group 1 and 28.6% in group 2. Only one retrograde nosocomial pneumonia developed (group 1). CONCLUSION: Based on our findings, we strongly recommend the adoption of sucralfate as opposed to no prophylaxis in the prevention of acute upper gastrointestinal ulceration. PMID- 7988132 TI - Peak systolic pressure/end-systolic volume ratio, a load-independent measure of ventricular function, is reversibly decreased in human septic shock. AB - OBJECTIVE: To evaluate left ventricular performance in patients with septic shock, using a load-independent measure of left ventricular systolic function, the peak systolic pressure/end-systolic volume index ratio. SETTING: National Institutes of Health research facility. DESIGN: Prospective study with retrospective analysis of data. PATIENTS: Twenty-seven patients with septic shock, 13 critically ill, nonseptic control patients, and nine normal volunteers. MEASUREMENTS: Hemodynamic measurements from indwelling arterial and pulmonary artery catheters and radionuclide-determined ejection fraction measurements. These data were used to calculate the peak systolic pressure/end-systolic volume index ratio in each patient group. The survivors and nonsurvivors of septic shock were evaluated on admission to the intensive care unit and at recovery in the survivors or within 24 hrs of death in the nonsurvivors. The ratio in each group was compared with the ratio in the critically ill, nonseptic patients and the normal volunteers. MAIN RESULTS: Both survivors and nonsurvivors of septic shock had a decreased peak systolic pressure/end-systolic volume index ratio (1.2 +/- 0.1 and 1.7 +/- 0.2 mm Hg/mL/m2, respectively) compared with critically ill, nonseptic patients (3.5 +/- 0.7 mm Hg/mL/m2; both p < .05) and normal volunteers (4.3 +/- 0.4 mm Hg/mL/m2; both p < .05). The differences between the groups were highly significant (p < .001) by analysis of variance. The survivors had a lower initial peak systolic pressure/end-systolic volume index ratio than the nonsurvivors (p < .05). In the survivors, the peak systolic pressure/end-systolic volume index ratio increased significantly (p < .05) with recovery to 2.4 +/- 0.3 mm Hg/mL/m2. Serial determinations of peak systolic pressure/end-systolic volume index ratio in the nonsurvivors did not show any significant change. CONCLUSIONS: This study confirms that survivors and nonsurvivors of septic shock have significant depression of myocardial performance as measured by a load independent technique. Survivors have greater depression of myocardial performance than nonsurvivors, and, with recovery, the ventricular performance in survivors increases toward normal values. PMID- 7988133 TI - Failure of pentoxifylline to ameliorate severe acute pancreatitis in the rat: results of a prospective, randomized, controlled study. AB - OBJECTIVE: To investigate the benefit of pentoxifylline in severe experimental pancreatitis. DESIGN: Prospective, randomized, controlled study. SETTING: Experimental animal laboratory in a University hospital. SUBJECTS: Forty-two adult male Sprague-Dawley rats. INTERVENTIONS: Acute pancreatitis was induced by supramaximal stimulation with cerulein plus a pressure and volume controlled 10 min intraductal infusion of 10-mM glycodeoxycholic acid. Thirty minutes after pancreatitis was induced, animals were randomized to receive pentoxifylline (60 mg/kg over 2.5 hrs), or saline. All animals received fluid resuscitation with lactated Ringer's solution (8 mL/kg/hr), and surviving animals were killed at 24 hrs. MEASUREMENTS AND MAIN RESULTS: There was a progressively significant decrease in mean arterial pressure after pancreatitis was induced, with no difference between pentoxifylline-treated rats and controls. Hematocrit increased significantly in both groups at 6 hrs, and returned to baseline values at 24 hrs. Ascites volume and levels of trypsinogen activation peptide in plasma and ascites were similar in both groups. Twenty-four hour mortality was 47% for the pentoxifylline group and 52% for the control group. Histologic scores for necrosis, edema, inflammation, and hemorrhage showed no significant differences between the two groups. CONCLUSION: Treatment with pentoxifylline failed to improve outcome in a model of severe acute pancreatitis in the rat. PMID- 7988134 TI - Effect of Intralipid on hypoxic and angiotensin-II induced pulmonary vasoconstriction in the isolated rat lung. AB - OBJECTIVE: Lipid infusions are reported to cause hypoxemia by increasing intrapulmonary shunt fraction. However, the mechanism by which they worsen gas exchange is unknown. We hypothesized that a reduction in hypoxic pulmonary vasoconstriction, caused by lipid infusion, could be the cause of increased shunt. DESIGN: A prospective, controlled laboratory study. SETTING: A postgraduate teaching hospital laboratory. SUBJECTS: Male Wistar rats weighing 250 to 300 g. INTERVENTIONS: Four separate series of experiments were performed: a) The pulmonary vasopressor response to angiotensin-II was compared before and after adding either 0.9% sodium chloride (control n = 5) or 20 microL of Intralipid (n = 8). b) The pulmonary vasopressor response to hypoxia (FIO2 of 0.3) was compared before and after either 0.9% sodium chloride (control n = 5) or 20 microL of Intralipid (n = 8). c) 1 microM of indomethacin was added before either 0.9% sodium chloride (control n = 5) or Intralipid (n = 5) and the hypoxic pulmonary vasoconstriction response was compared. d) 10(-3) M L-monomethyl-n arginine was added before 20 microL of Intralipid and the hypoxic pulmonary vasoconstriction response was compared (n = 5). MEASUREMENTS AND MAIN RESULTS: Changes in pulmonary arterial pressure were measured before and after interventions. Intralipid reduced the angiotensin-II pressor response by 36 +/- 3% (p = .005) and the hypoxic pulmonary vasoconstriction response by 50 +/- 2% (p = .0003). This action was not blocked by pretreatment with either indomethacin or L-monomethyl-n-arginine. CONCLUSIONS: Intralipid reduces the hypoxic pulmonary vasoconstriction response in the isolated, blood perfused rat lung. This action is nonspecific, as shown by a similar reduction in the pulmonary pressor response to angiotensin-II. Pharmacologic blockade of prostaglandin release, by indomethacin, and nitric oxide release, by L-monomethyl-n-arginine did not prevent the reduction in hypoxic pulmonary vasoconstriction, thereby suggesting that neither agent mediates the lipid-induced change in pulmonary vasoreactivity. PMID- 7988135 TI - Tumor necrosis factor-alpha alters phospholipid content in the bronchoalveolar lavage-accessible space of isolated perfused rat lungs. AB - OBJECTIVES: To examine the effect of tumor necrosis factor-alpha (TNF-alpha) on pulmonary artery pressure and on total protein, phospholipid, lysophosphatidylcholine, phosphatidylcholine, phosphatidylinositol, and phosphatidylglycerol content in the bronchoalveolar lavage-accessible space of the isolated perfused rat lung, and to evaluate the role of the lung in the clearance of TNF-alpha from the perfusion medium in this model. DESIGN: Prospective, controlled trial. SETTING: Research laboratory. SUBJECTS: Adult male Sprague-Dawley rats. INTERVENTIONS: The lungs from all subjects were isolated, perfused, and ventilated in the same manner. After a baseline sampling bronchoalveolar lavage, a reduction bronchoalveolar lavage was performed to establish a uniform amount of phospholipid in all lungs. This procedure was followed by the zero time sampling bronchoalveolar lavage, which verified the efficacy of the reduction lavage. After 5 mins, isoproterenol was added to the perfusion medium to promote surfactant secretion. Five minutes later, TNF-alpha (experimental group) and/or its carrier solution (control group) was added to the perfusion medium. Sampling bronchoalveolar lavages were repeated at 1 and 2 hrs after the zero time. Bronchoalveolar lavage samples were subsequently analyzed for protein and phospholipid content. After each sampling bronchoalveolar lavage, perfusion medium was obtained for immediate determinations of pH and the partial pressures of oxygen and carbon dioxide and the subsequent determination of TNF alpha content. Pulmonary arterial pressures were continuously measured. MEASUREMENTS AND MAIN RESULTS: The pH and PCO2 in the perfusion medium remained in the physiologic range for all lungs, while the PO2 remained consistently increased. Mean pulmonary arterial pressures did not differ between groups. TNF alpha levels were constant throughout the 2-hr period in the experimental group, and no TNF-alpha was detected in the perfusion medium of the control group. Amounts of total protein, total phospholipid, and lysophosphatidylcholine did not differ between the two groups. Although not statistically significant, phosphatidylglycerol was lower in the experimental group (p < .07). An increase in phosphatidylinositol content in the experimental group with a concomitant decrease in the control group between 60 and 120 mins was noted (p < .01). Amounts of phosphatidylcholine were found to be lower in the experimental group throughout the 2-hr period (p < .02). CONCLUSIONS: a) TNF-alpha alters the amounts of phosphatidylcholine, phosphatidylinositol, and possibly phosphatidylglycerol present in the lavage-accessible space of the isolated perfused rat lung. Possible mechanisms might include a direct effect of TNF-alpha on phospholipid secretion and/or reuptake, or an indirect effect via alteration of the type II pneumocytes' response to beta-adrenergic receptor stimulation. b) Increases in pulmonary arterial pressures seen in vivo with TNF-alpha administration are not due to a direct effect. Alterations in cardiac function or the interaction of other agents may be necessary to develop changes in pulmonary arterial pressure. c) This in vitro model does not demonstrate the rapid clearance of TNF-alpha from the circulation that is seen in vivo, suggesting that TNF-alpha metabolism does not occur primarily in the lung. Our findings support the hypothesis that TNF-alpha may alter surfactant composition, which may in turn contribute to the development of the adult respiratory distress syndrome. PMID- 7988136 TI - Effect of neuromuscular blockade on the elastic properties of the lungs, thorax, and total respiratory system in anesthetized pigs. AB - OBJECTIVE: To evaluate the effect of neuromuscular blockade on the elastic properties of the lungs, thorax, and total respiratory system in pigs anesthetized to suppress spontaneous breathing. DESIGN: Prospective, randomized, experimental study. SETTING: A research laboratory at a university medical center. SUBJECTS: Eight healthy, anesthetized pigs, weighing 22 to 25 kg. INTERVENTIONS: Pigs, with and without muscular blockade, were mechanically ventilated during an infusion of sodium pentobarbital that was titrated to suppress spontaneous breathing activity. MEASUREMENTS AND MAIN RESULTS: No significant differences were observed between pressure/volume curves of the lungs, the chest wall, and the total respiratory system, as determined by inflating and deflating the lungs during anesthesia, with or without neuromuscular blockade, in random order. Functional residual capacity was 985 +/- 87 mL with neuromuscular blockade and 997 +/- 78 mL without neuromuscular blockade (NS). A comparison of the total respiratory system, lung, and chest wall compliances obtained with and without neuromuscular blockade showed high correlations (total respiratory system compliance [r2 = .86]; chest wall compliance [r2 = .83]). CONCLUSION: Neuromuscular blockade does not alter the elastic properties of the lungs, chest wall, or total respiratory system in mechanically ventilated pigs receiving sodium pentobarbital anesthesia to suppress spontaneous breathing efforts. PMID- 7988137 TI - Reversal of vagal tone in conjunction with high-dose epinephrine in a canine asphyxial pulseless electrical activity model. AB - OBJECTIVE: To investigate the effects of surgical vagotomy in conjunction with high-dose epinephrine (0.2 mg/kg) on return of spontaneous circulation rates in a canine model of asphyxial pulseless electrical activity. DESIGN: Prospective, controlled laboratory investigation, using an asphyxial canine cardiac arrest model randomized to receive bilateral cervical vagotomy or no vagotomy. SETTING: Emergency medicine animal research laboratory. SUBJECTS: Sixteen mongrel dogs weighing 15 to 25 kg. INTERVENTIONS: Pulseless electrical activity arrest was induced by clamping the endotracheal tube. All animals remained in untreated pulseless electrical activity for 10 mins and then were randomized to receive bilateral cervical vagotomy (n = 8) or no vagotomy (n = 8). All animals received standard external cardiopulmonary resuscitation and high-dose epinephrine (0.2 mg/kg every 5 mins) throughout resuscitation. MEASUREMENTS AND MAIN RESULTS: The electrocardiogram complex rate, arterial blood gases, and coronary perfusion pressure during resuscitation were not statistically different between groups. Return of spontaneous circulation was achieved in 88% (7/8) of the no vagotomy vs. 63% (5/8) of the vagotomy animals (p = NS). All animals that achieved return of spontaneous circulation survived 1 hr. CONCLUSIONS: In conjunction with high dose epinephrine, vagotomy did not improve the return of spontaneous circulation rate in this pulseless electrical activity arrest model. Additionally, the hemodynamic effects of high-dose epinephrine overshadowed the effects of vagotomy. PMID- 7988138 TI - Neurologic outcome and heart resuscitability with closed-chest cardiopulmonary bypass after prolonged cardiac arrest times in rabbits. AB - OBJECTIVES: To observe the influence of prolonged cardiac arrest times on neurologic outcome and heart resuscitability, using a resuscitation model with cardiopulmonary bypass in the rabbit, and to determine whether the changes in the plasma concentrations of lactate and lipoperoxide correlate with the severity of global brain ischemia. DESIGN: Randomized, prospective, controlled animal trial. SETTING: University research laboratory. SUBJECTS: Forty-three New Zealand white rabbits. INTERVENTIONS: Rabbits were randomly assigned to one of five groups: control, and four groups with cardiac arrest times of 8, 10, 12, and 15 mins. A bolus of 4 to 6 mL of 0.5-M potassium chloride was injected into the right atrium to induce cardiac arrest within 5 secs. Resuscitation was performed using closed chest cardiopulmonary bypass, and mechanical ventilation with pure oxygen. When necessary, a DC shock of 10 joules/kg was used to terminate ventricular fibrillation. MEASUREMENTS AND MAIN RESULTS: Hemodynamics, electroencephalogram, electrocardiogram, and return times of various cranial reflexes were observed throughout the experiment. Plasma concentrations of lactate and lipoperoxide were determined before cardiac arrest and 5, 30, 90, and 150 mins after resuscitation. The neurologic outcome, measured by Neurologic Deficit Score, was determined at 150 mins postresuscitation. Values for the Neurologic Deficit Score were: 8 +/- 8 in the control group; 31 +/- 13; 37 +/- 19; 69 +/- 22; and 62 +/- 26 in the cardiac arrest groups of 8, 10, 12, and 15 mins, respectively. No significant differences in cardiac resuscitability were found among the four cardiac arrest groups. The plasma concentrations of lactate and lipoperoxide were significantly higher than the prearrest levels; however, there were no significant differences among the four cardiac arrest groups. CONCLUSIONS: Cardiopulmonary bypass can be used to establish a resuscitation model in rabbits. Neurologic outcome worsens progressively in proportion to the prolonged cardiac times, especially when it exceeds 10 mins. Cardiac resuscitability is still possible, even when arrest time exceeds 15 mins. Changes in plasma concentrations of lactate and lipoperoxide do not correlate with the neurologic outcome and heart resuscitability following cardiac arrest. PMID- 7988139 TI - An in vitro evaluation of an instrument designed to measure oxygen consumption and carbon dioxide production during mechanical ventilation. AB - OBJECTIVE: To determine the ability of the Puritan-Bennett 7250 metabolic monitor to measure CO2 production and oxygen consumption (VO2) under simulated clinical conditions. DESIGN: An in vitro validation study. SETTING: Laboratory of a large university medical center. METHODS: An in vitro evaluation was performed by adding precise amounts of CO2 and nitrogen to a lung model to simulate CO2 production and VO2. CO2 production and VO2 values measured by the metabolic monitor were compared with simulated values at various FIO2 values (0.21 to 0.80), levels of positive end-expiratory pressure (0 to 20 cm H2O), and flow-by mode flow rates (0 to 20 L/min). This comparison was also made at increased peak airway pressures (60 cm H2O). The effects of various concentrations of oxygen on the accuracy of the CO2 production measurements were also examined. RESULTS: The measurements made by the instrument were within 7% of values predicted from the CO2 and nitrogen infusions. There was no effect of various oxygen concentrations on the accuracy of CO2 production measurements. CONCLUSION: Under the in vitro conditions tested, the metabolic monitor provided accurate measurements of VO2 and CO2 production. PMID- 7988141 TI - Critical care medicine: observations from the Department of Veterans Affairs' intensive care units. AB - OBJECTIVES: To study the critical care medicine programs of the Department of Veterans Affairs. DESIGN: Survey study. SETTING: Data were obtained from 85% (113/133) of the acute care hospitals of the Department of Veterans Affairs. MAIN MEASURES: Intensive care unit (ICU) administrative and patient demographics, physician training and certification, participation in critical care medicine programs and research. RESULTS: Analyses were performed on 78% (2021) of Department of Veterans Affairs' ICU beds. Mortality (%) was highest in medical ICUs (11.7 +/- 0.8) and lowest in coronary care units (5.0 +/- 0.5) and surgical ICUs (5.5 +/- 0.5). The average length of stay (days) was highest in medical ICUs (5.6 +/- 0.6) and lowest in combined medical-coronary care units (4.2 +/- 0.4) and coronary care units (4.3 +/- 0.5). The majority of ICU directors have internal medicine training. A minority of ICU directors are formally trained in critical care medicine or are board eligible or certified in critical care medicine. The majority of fellows in the ICU are pulmonary or cardiac fellows; a minority are critical care medicine fellows. Accredited critical care medicine fellowship training programs were found in only 17% (19/113) of responding Department of Veterans Affairs' institutions. Seventy-three percent (82/113) of ICUs in responding hospitals had published fewer than five publications between 1987 and 1990. CONCLUSIONS: The results of this study suggest that the Department of Veterans Affairs would benefit from increasing the number of critical care medicine board eligible/certified directors, and increasing the program's participation in accredited critical care medicine fellowship training programs and research endeavors. Overall, however, we conclude that the Department of Veterans Affairs' critical care medicine program is at least comparable to nationwide ICUs in the parameters evaluated. PMID- 7988140 TI - Federal and nationwide intensive care units and healthcare costs: 1986-1992. AB - OBJECTIVES: To establish Department of Veterans Affairs' intensive care unit (ICU) costs from a database and to use this information to validate the Russell equation, the most commonly used method of calculating ICU costs. To compare and trend Department of Veterans Affairs' and nationwide (USA) ICU and healthcare costs. DESIGN: Comparison study. SETTING: Database analysis of Department of Veterans Affairs' and nationwide ICUs over a 6-yr period (1986-1992), with biennial evaluations. MAIN MEASURES: Costs and bed occupancies of Department of Veterans Affairs' and nationwide hospitals and ICUs, as well as United States national health expenditures and gross domestic product. RESULTS: Fifty percent to Department of Veterans Affairs' ICU funds were used for nurse and physician salaries. Department of Veterans Affairs' ICU direct and indirect cost ratios have remained constant (2:1). The Russell equation is valid, providing that the "inpatient only" cost variable is used. ICU costs were consistently lower in the Department of Veterans Affairs' than nationwide, as compared by the Russell equation. A smaller fraction of the hospital budget was allocated to the ICU in the Department of Veterans Affairs than in nationwide institutions. Despite an increasing nationwide ICU patient workload, the percentage of ICU fund allocations has not increased. Health care in the United States increases at a rate greater than the increase in gross domestic product. Healthcare delivery costs are increasing at a greater rate nationwide than in the Department of Veterans Affairs. The percentage increase in ICU cost per day, both in the Department of Veterans Affairs and nationwide, was less than the increase in healthcare costs. The percent of the gross domestic product, national health expenditure, and hospital cost used by the ICU has increased minimally during the course of this study. CONCLUSIONS: The Department of Veterans Affairs has the only national ICU line item cost database available. For the Russell equation calculation to be accurate, inpatient only costs should be used. Until customized Health Care Financing Administration analyses become available, nationwide ICU costs are best determined by the Russell equation. Department of Veterans Affairs' ICUs have a consistent cost advantage over nationwide ICUs. Increases in United States healthcare delivery costs continue to exceed the increase in gross domestic product. Cost containment is already occurring in critical care. PMID- 7988142 TI - Health system reform and the critical care practitioner. PMID- 7988143 TI - Joint position statement: essential provisions for critical care in health system reform. Society of Critical Care Medicine. American Association of Critical Care Nurses. AB - OBJECTIVE: Production of a statement defining the essential provisions of health system reform as determined by the Society of Critical Care Medicine (SCCM) and the American Association of Critical-Care Nurses (AACN). This document is the only nurse-physician joint statement to result from the 1994 health system reform debate. DATA SOURCES: A joint SCCM-AACN working group developed the document. Working group members referenced position papers previously developed by SCCM and AACN. DATA SYNTHESIS: Working group members refined drafts of the statement until a consensus was reached. Final versions of the paper were reviewed and endorsed by the SCCM Council and the AACN Board of Directors. CONCLUSIONS: SCCM and AACN agreed that health system reform should ultimately achieve universal coverage, access, control cost, and should improve the quality of care. SCCM and AACN endorsed improved access to and coverage for preventive care services. Recognizing that critical illness and injury cannot be prevented entirely, SCCM and AACN agreed that a reformed system must foster improved care of the critically ill and injured as described below. PMID- 7988144 TI - Delayed recognition of esophageal intubation in a neonate: role of radiologic diagnosis. PMID- 7988145 TI - What is right ventricular (dys)function? PMID- 7988146 TI - Prognosis in comatose patients with acute supratentorial mass lesions. PMID- 7988147 TI - Pediatric Risk of Mortality Score underestimates the requirement for intensive care during interhospital transport. PMID- 7988148 TI - High-dose epinephrine in cardiopulmonary resuscitation: are we missing the question? PMID- 7988149 TI - Aerosolized ribavirin in mechanically ventilated children. PMID- 7988150 TI - Ultrastructure of IVM-IVF bovine blastocysts vitrified after equilibration in glycerol 1,2-propanediol using 2-step and 16-step procedures. AB - Two experiments were conducted to investigate the relationship between survival rates and ultrastructural appearance, using the freeze-replica technique, of bovine blastocysts after vitrification. In experiment 1, blastocysts obtained from in vitro-matured and in vitro-fertilized (IVM-IVF) bovine oocytes were either equilibrated in a stepwise manner in a vitrification solution (VS; 22.5% glycerol + 22.5% 1,2-propanediol) using 16 steps for 18 min in total (the 16-step method) or equilibrated with 10% glycerol + 20% 1,2-propanediol for 10 min and then exposed to VS (the 2-step method). The blastocysts were then vitrified by plunging them into liquid nitrogen. All samples were subsequently thawed in a water bath at 37 degrees C and cultured in vitro with a monolayer of cumulus cells. The survival rate obtained for blastocysts equilibrated by the 16-step method was 83.3% (25/30). In contrast, no blastocysts survived by the 2-step method (0/30). In experiment 2, freeze-replica observations were carried out on blastocysts vitrified by the 16-step method and the 2-step method. In all the blastocysts, no ice crystals were observed in the cytoplasm, blastocoelic cavity, or extracellular areas, which confirmed the occurrence of complete vitrification. Little ultrastructural change was observed in the plasma membrane of the blastocysts equilibrated by the 16-step method. In contrast, small vesicles and distinct intramembrane particle (IMP) aggregation were frequently observed in the plasma membranes of blastocysts equilibrated by the 2-step method. These results indicate that the successful cryopreservation of blastocysts following the 16 step equilibration requires not only complete vitrification, but also minimization of ultrastructural damage to the plasma membrane. PMID- 7988151 TI - The effect of temperature at which slow cooling is terminated and of thawing rate on the survival of one-cell mouse embryos frozen in dimethyl sulfoxide or 1,2 propanediol solutions. AB - We investigated the slow freezing of one-cell mouse embryos with either dimethyl sulfoxide (Me2SO) or 1,2-propanediol (PROH) as the cryoprotectant. One-cell embryos, collected from superovulated C57BL/6J x CBA/Ca females were exposed to 1.5 M solutions of either Me2SO or PROH. The embryos were cooled at 0.3 degrees C/min to temperatures between -10 degrees and -80 degrees C before being plunged into LN2 and then warmed at either 20 degrees C/min or 450 degrees C/min. Survival was expressed as the percentage of hatching or hatched blastocysts per frozen-thawed embryo. When the slow cooling was in 1.5 M PROH, the temperature at which survival rates after slow thawing began to increase was -35 degrees C (52.6 +/- 5.2% survival). For slow cooling in 1.5 M Me2SO this temperature was -50 degrees C (45.0 +/- 2.9% survival). The addition of sucrose to the 1.5 M PROH solution raised the temperature at which survival rates after slow thawing began to increase to -30 degrees C (54.8 +/- 3.7% survival). If slow cooling was stopped at high subzero temperatures, embryos survived better after rapid thawing than slow thawing. If slow cooling was stopped at low subzero temperatures, the survival rate was not dependent on the thawing rate if freezing was done in 1.5 M PROH. When freezing was in Me2SO solutions and to subzero temperatures of -60 degrees and -80 degrees C, slow thawing gave better survival than rapid thawing. The addition of sucrose to the Me2SO freezing solution restored the survival rates at -60 degrees and -80 degrees C. These results indicate that high rates of survival may be obtained from one-cell mouse embryos by a rapid or a slow thawing procedure, as has been found for other developmental stages. The results also indicate that PROH provides superior protection compared to Me2SO against freezing-thawing damage and that the addition of sucrose to the freezing solutions prior to freezing improves the overall survival rates. Embryos that survived freezing and developed in culture implanted and formed normal fetuses at rates similar to those of nonfrozen control embryos (60% vs 68% and 53% vs 58%, respectively. PMID- 7988152 TI - The effects of hepatic preservation at 0 degrees C compared to 5 degrees C: influence of antiproteases and periodic flushing. AB - The optimal preservation temperature for liver allografts is unknown. We evaluated the effect of small differences in preservation temperature, 5 degrees C vs 0 degrees C, on outcome of prolonged preservation. Livers of Wistar rats were preserved at these temperatures in UW solution for 40 h. Function was studied during reperfusion on the isolated perfused rat liver system at 37 degrees C. To compare the effects of a small reduction in temperature with known beneficial strategies, the effects of including antiproteases and periodic flushing of the graft with UW solution during cold preservation at 5 degrees C were also studied. Aspartate transaminase (AST) and alanine transaminase release after 4 h of reperfusion were much higher in the livers stored at 5 than at 0 degrees C (P < 0.0005). Addition of antiproteases to the preservation solution or periodic flushing reduced AST release but neither treatment at 5 degrees C was as good as simple storage at 0 degrees C. Cumulative bile production after 4 h of reperfusion was significantly greater in the 0 degrees C preserved group than in liver at 5 degrees C or 5 degrees C with periodic flushing. The addition of antiproteases resulted in slightly increased bile production (not significant). Platelets and WBCs in the perfusate decreased during reperfusion. This effect was more pronounced in the 5 degrees C preserved livers than in those stored at 0 degrees C. Antiproteases in the preservation solution appeared to inhibit platelet and WBC loss. Perfusate flow was significantly higher in the 0 degrees C group. We conclude that small differences in preservation temperature even at these low temperatures are important in postreperfusion liver function. PMID- 7988153 TI - Glycolysis and energy metabolism in rat liver during warm and cold ischemia: evidence of an activation of the regulatory enzyme phosphofructokinase. AB - The current study was undertaken so that the effects of both ischemia and ischemia + hypothermia could be examined in mammalian liver. Particular reference was made to the function of glycolysis, which is the only mechanism for energy production under these conditions. The response of adenylate pools reflected the energy imbalance created during warm ischemia within minutes of organ isolation. ATP levels and energy charge values for control (freshly isolated) livers were 1.20 +/- 0.07 and 0.49 +/- 0.02 mumol/g. Within 5 min of warm ischemia, ATP levels had dropped well below control values and by 30 min warm ischemia, ATP, AMP, and E.C. values were 0.21, 2.01, and 0.17 mumol/g, respectively. Cold ischemic livers (flushed with Marshall's citrate solution and stored on ice) exhibited similar, but more protracted, patterns of adenylate depletion (ATP and ADP) and accumulation (AMP). In both warm and cold ischemic livers, levels of fructose-6-phosphate (F6P) and fructose-1,6-bisphosphate (F1,6P2) indicated a marked activation of glycolysis at the phosphofructokinase (PFK) locus after a certain time of ischemia. Although the activations occurred at different times (30 min and 10 h for warm and cold ischemic livers, respectively), the patterns of change in levels of glycolytic metabolites associated with the PFK-catalyzed reaction were similar; levels of F6P dropped and F1,6P2 increased. Changes in metabolite levels (phosphoenol pyruvate and pyruvate) associated with another key suspect regulatory enzyme, pyruvate kinase, indicated no role in regulatory control of glycolysis during warm or cold ischemia. The activation of PFK at 30 min and 10 h of warm and cold ischemia, respectively, may reflect the accumulating effects of loss of intracellular homeostasis, which leads to impending irreversible damage. PMID- 7988154 TI - Response of epithelial (MDCK) cell junctions to calcium removal and osmotic stress is influenced by temperature. AB - Intercellular junctions could be targets of injury during both hypothermic storage and cryopreservation. Monolayers of Madin-Darby canine kidney (MDCK) cells, an epithelial cell line, were grown on microporous membrane filters, and junction integrity was monitored by transepithelial electrical resistance (TER). At 37 degrees C, TER was 196 ohm . cm2 (SD 58, n = 59): this rose with falling temperature to 278 (SD 54) and 409 (SD 110) ohm . cm2, respectively, at 22 and 0 degrees C. This initial increase was accounted for solely by the change in conductivity of the bathing medium, which declined with falling temperature. Prolonged exposure to reduced temperature, however, did cause a gradual decline in TER. Removal of calcium at 22 degrees C caused a rapid fall in TER owing to dissociation of calcium-dependent components of the junctional complex. This was followed by a gradual increase in TER over several hours when calcium was restored to the bathing medium. At 0 degrees C, TER declined slowly regardless of the presence or absence of calcium, which suggested that reduced temperature stabilized junctions with respect to their calcium dependence, but that low temperature itself was causing dissociation of junctions. Hypertonic stress (597 mOsmol/kg) caused a reduction in TER both at 22 and 0 degrees C, which, unlike the reduction caused by calcium removal at 22 degrees C, was reversed relatively rapidly on return to isotonic conditions. Hypotonic stress (201 mOsmol/kg) increased TER at 0 degree C, but had no effect at 22 degrees C. The lack of response at the higher temperature might have been the result of a cell volume regulatory mechanism.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7988155 TI - Dimethyl sulfoxide concentration in fresh and cryopreserved porcine valved conduit tissues. AB - The time-dependent penetration of the cryoprotectant dimethylsulfoxide (DMSO) into porcine aortic conduit and the effectiveness of dilutional removal of cryoprotectant from these tissues were evaluated using high performance liquid chromatography. Incubation of intact conduit tissues in 1.4 mol/liter (10%) DMSO at 4 degrees C revealed that the cryoprotectant penetrated the tissues in a nonlinear time-dependent manner requiring 80 to 120 min to achieve a tissue concentration of approximately 0.7 mol/liter tissue water volume. This concentration approximated 54% of the theoretical media concentration (1.3 mol/liter) occurring through dilution effects of addition of the tissue to the medium. The osmolality of the medium decreased linearly in a time-dependent manner from 2975 to 2860 mOsmol/kg water over 80 min for a negative slope of 1.28 mOsmol/kg water/min. Analysis of the concentrations of DMSO in tissues undergoing dilutional removal at 4 degrees C revealed that dilutional removal at low temperatures may not be an effective means of removing DMSO from cryopreserved cardiovascular tissues. It requires approximately 40 to 50 min at 4 degrees C for tissue concentrations of DMSO to be reduced to 0.24 mol/liter tissue water volume, which is far in excess of the concentration expected to be present in the tissue and suspending solution (< 0.03 mol/liter media) at equilibrium. It is suggested that protocols for removal of DMSO from thawed allograft heart valves which do not allow the temperature to increase above 4 degrees C during the removal process may not provide sufficient incubation time to permit the cryoprotectant (DMSO) to diffuse from the tissues during a clinical post-thawing preparation for clinical transplantation. PMID- 7988156 TI - Effects of cryopreservation on immune responses: VII. Freezing induced enhancement of IL-6 production in human peripheral blood mononuclear cells. AB - To better understand the effects of freezing on various immunocompetent cell functions, the interleukin-6 (IL-6)-producing activities of frozen peripheral blood mononuclear cells (PBMCs) from healthy subjects were determined. Frozen, lipopolysaccharide (LPS)-activated PBMCs produced significantly larger quantities of IL-6 than fresh cells. Although elimination of radiosensitive, CD8+ suppressor T cells had no significant effect on PHA-induced IL-6 production by T cells, elimination of CD4+ Leu-8+ suppressor T cell subsets resulted in a significantly enhanced IL-6 secretion. Exogenous addition of prostaglandin E-2 to frozen PBMCs and monocytes inhibited LPS-induced IL-6 production. The results suggest that functional inactivation of a subset of cryosensitive, PGE-2-secreting monocytes is associated with an increase in IL-6 production by the other subset. They also indicate that a subset of CD4+ Leu-8+ T cells might be involved in feedback inhibition of PHA-induced T cell-mediated IL-6 production. The results provide further evidence that the presence of larger quantities of IL-6 in conjunction with increased amounts of IL-1 and IL-2 secreted by the frozen cells may be responsible for the previously reported enhanced immunoglobulin-producing abilities of frozen cells from clinically healthy subjects and from patients with lung cancer. PMID- 7988157 TI - Cryopreservation of human bone marrow after purging T-cells or tumor cells. AB - Bone marrow transplantation (BMT) is a valuable measure for treatment of leukemia. In order to reduce, even to eliminate, the graft versus host disease after allogenic BMT and prevent the reinfusion of tumor cells during autologous BMT, the cryopreservation of human BM after purging T-cells with immunotoxin or purging tumor cells with monoclonal antibody 55 (McAb55) was studied. Results demonstrated that: (1) treatment with McAb55 and rabbit complement (RC) did not affect the GM-CFU of BM, but treatment with immunotoxin slightly decreased the GM CFU of BM; (2) a freeze-thawing procedure obviously decreased the GM-CFU number of BM, the GM-CFU numbers of frozen BM samples were lower than those of the nonfrozen samples; (3) there were no differences in GM-CFU numbers between normal BM and BM treated with McAb55 and RC when the cooling rate used was the same; (4) there was a negative linear correlation between cooling rates and GM-CFU numbers of BM in the cooling rate range used and the optimal cooling rate for the cryopreservation of normal BM and BM treated with McAb55 and RC or immunotoxin was the same, namely, 0.5 degrees C/min. PMID- 7988158 TI - Mechanical interactions between ice crystals and red blood cells during directional solidification. AB - Experiments in which red blood cells were frozen on a directional solidification stage under a microscope show that there is a mechanical interaction between ice crystals and cells in which cells are pushed and deformed by the ice crystals. The mechanical interaction occurs during freezing of cells in physiological saline and is significantly inhibited by the addition of 20% v/v glycerol to the solution. The addition of osmotically insignificant quantities of antifreeze proteins from the winter flounder or ocean pout to the physiological saline with 20% v/v glycerol generates strong mechanical interactions between the ice and the cells. The cells were destroyed during freezing in physiological saline, survived freezing in physiological saline with glycerol, and were completely destroyed by the addition of antifreeze proteins to the solution with glycerol. The difference in cell survival through freezing and thawing appears to be related, in part, to the habit of ice crystal growing in the suspension of red blood cells and the nature of mechanical interaction between the ice crystal and the cells. This suggests that mechanical damage may be a factor during cryopreservation of cells. PMID- 7988159 TI - Cardiac rhythm disturbances due to caval occlusion during hepatic cryosurgery. AB - Cryoablation is used to treat inoperable hepatic malignancy. We investigated the safety of cryoablation close to the inferior vena cava. Our sheep model showed that it was impossible to create an iceball around the inferior vena cava (IVC) unless this vessel was clamped. When subsequently the IVC was clamped and frozen for 30 min, the anesthetized spontaneously breathing sheep (n = 3) exhibited cardiac arrhythmias typical of hyperkalemia on release of the clamp. The plasma potassium in these sheep rose from a baseline mean (SD) of 5.0 (0.7) mmol/liter to 9.5 (0.9) mmol/liter after release of the clamp at the end of the freeze. These sheep also developed acute hypercapnoea and acidosis. These changes were avoided in subsequent sheep by assisting ventilation mechanically and hyperkalemia and arrhythmias were not seen in this group. Iceball cracking did not occur and the IVC remained intact in all cases. This work suggests that during hepatic cryotherapy of lesions close to the IVC, intraoperative monitoring of potassium is indicated, particularly if caval occlusion is required to achieve adequate iceball thermal distribution. PMID- 7988160 TI - Fractures in cryopreserved arteries. AB - The common carotid artery of the rabbit, a typical small elastic artery, can be cryopreserved using dimethyl sulfoxide, slow cooling, storage at less than -160 degrees C, and rapid warming. This technique provides satisfactory preservation of muscle and endothelial cells, but in about 75% of cases, gross circumferential fractures occur in the vessel wall. This paper investigates the influence of vehicle solution composition, cryoprotectant concentration, cooling rate, and storage temperature on the occurrence of cracks. When cooling was halted at -80 degrees C and the arteries were stored at this temperature, fractures no longer occurred. Possible mechanisms are discussed and it is proposed that mechanical stresses develop in the vitreous material that separates the ice crystals and lead to structural failure. PMID- 7988162 TI - The Sumithrayo strategy for the reduction of suicide in Sri Lanka. PMID- 7988161 TI - Assisted suicide among psychiatric patients in The Netherlands. PMID- 7988163 TI - Letters across the Atlantic. PMID- 7988164 TI - Suicide and terminal illness: lessons from the HIV pandemic. PMID- 7988165 TI - Jail suicide: overcoming obstacles to prevention. PMID- 7988166 TI - Kurt Cobain. PMID- 7988168 TI - Suicide intervention training evaluation: a preliminary report. AB - To date, very little work has been done on evaluating training in suicide intervention. This study developed and piloted a comprehensive method for evaluating suicide intervention training by applying three studies of immediate training effects on (a) suicide intervention abilities, (b) attitudes to suicide and suicide intervention, and (c) knowledge about suicide. The focus of the evaluation was a broadly used 2-day suicide intervention training program. Changes in suicide intervention abilities were measured by the Suicide Intervention Response Inventory (SIRI) and by performance in simulated suicide intervention situations, scored with the Suicide Intervention Protocol (SIP). Subjects consisted of 19 workshop participants in a pre-post condition and 17 participants in a post-test only condition. Results indicated significant increases in skills in suicide intervention situations. No significant effects were noted on the SIRI. Results from the attitudes and knowledge studies were very preliminary. They are reported here so that others may become aware of the methodology being used and the status of evaluation of the target program. Implications for further research are discussed. PMID- 7988167 TI - Correspondence as adjunct to crisisline intervention in a suicide prevention center. AB - A volunteer correspondence service was implemented in a suicide prevention center for certain frequent callers who phoned repeatedly, but whose situation did not improve. The interest in such a measure was fostered by feelings of inadequacy in a number of volunteers about handling frequent callers, which some researchers think accounts for volunteers' burnout and the high turnover. Five frequent callers with a moderate to low suicidal risk began a 6-month written correspondence with five experienced volunteers, no restrictions being made on their use of the crisisline. The frequency and length (minutes) of calls per month to the crisisline dropped for most of the callers, and the suicidal urgency of their calls remained moderate. The participants reported that rereading their correspondent's letters in times of distress had a soothing effect. In spite of having to deal with some reputedly difficult-to-manage frequent callers, all volunteers wished to renew their involvement in the correspondence service. Other suicide prevention centers are invited to experiment with this innovative type of adjunct intervention. PMID- 7988169 TI - Repeated suicidal behavior: a two-year follow-up. AB - The majority of suicide attempters repeat the suicidal act at least once. The study described here on a Danish sample of suicide attempters shows that 31% had made only one attempt. More repeaters than nonrepeaters were divorced, and more repeaters also lived alone or alone with children. The two groups did not differ significantly as to level of education, but were clearly different with regard to their economic activity. These differences cannot be used as a basis for the prediction of future suicidal behavior, since the factors discussed refer to characteristics that define suicide attempters in general. However, they do point to conditions that might be targets for intervention and aftercare. PMID- 7988170 TI - Assessing the "modeling effect" in parasuicidal behavior: a comment on Platt (1993) AB - This article provides a critical evaluation of Platt's [1993] research investigating the role of modeling in the acquisition of parasuicidal behavior. The discussion focuses on general theoretical and methodological issues related to research in this area, as well as on specific concerns regarding Platt's investigation. In addition to presenting a critique of this research, a hypothetical model is presented that should lend credibility to future investigations into the theoretically posited casual relationships within the modeling paradigm. Model selection was based upon a recognition that an adequate test of the observational learning theory would need to appropriately employ correlational data commonly found in research in suicide and parasuicide. The implications for clinical practice are presented. PMID- 7988171 TI - Conference report: attempted suicide in Europe. PMID- 7988172 TI - Controversial issues in the ethics and limitations of suicide prevention. PMID- 7988174 TI - The quest for continual recertification. PMID- 7988173 TI - Interventional musculoskeletal radiology. AB - Interventional procedures constitute a significant proportion of musculoskeletal radiology. Percutaneous needle biopsy is the ultimate diagnostic technique for the evaluation of musculoskeletal neoplasms and infections. The procedure is accurate, rapid, and safe. It is ideally suited for the diagnosis of metastatic disease and round cell neoplasms. Several needle procedures have been used for the diagnosis and treatment of low back pain. Diskography is primarily a diagnostic test used to determine the symptomatic disk level when multilevel disk disease is present and also to diagnose internal disk disruption. Nerve block with local anesthetic is also used to locate the symptomatic level in patients with multilevel abnormalities. Epidural steroid injection is a therapeutic procedure that commonly is used in patients with low back pain and has been shown to be most effective in patients with disk herniation. Facet joint injection with local anesthetic and steroid is performed to diagnose and treat the facet syndrome. Other needle procedures in the musculoskeletal system include sacroiliac joint aspiration and injection, prosthetic joint aspiration to evaluate potential infection, distention arthrography, and injections of the coccyx for coccydynia. PMID- 7988175 TI - Should bystanders perform mouth-to-mouth ventilation during resuscitation? PMID- 7988176 TI - What is this thing called RADS? PMID- 7988177 TI - Using functional status to assess treatment outcomes. PMID- 7988178 TI - To live, to keep alive, to let die. PMID- 7988179 TI - Right ventricular dilatation, right ventricular wall thickening, and Doppler evidence of pulmonary hypertension in patients with a pure restrictive ventilatory impairment. AB - The purpose of this investigation was to determine the severity of pure restrictive ventilatory impairment that results in right ventricular (RV) dilatation, increased RV wall thickness, and pulmonary hypertension. Two dimensional (2-D) echocardiography, Doppler measurements of pulmonary flow, and spirometry were performed on 26 unselected patients (17 female, 9 male) with a pure restrictive ventilatory impairment. A restrictive ventilatory impairment was defined as a forced vital capacity (FVC) < or = 80 percent predicted with a normal FEV1/FVC ratio (FEV1 = 1 s forced expiratory volume). The patients were grouped according to the severity of the restrictive ventilatory defect: mild (FVC, 65 to 80 percent predicted), moderate (FVC, 51 to 64 percent predicted), and severe (FVC < or = 50 percent predicted). An increased RV area (> 20.4 cm2) was shown in 0 of 10 (0 percent) patients with a mild impairment, 6 of 12 (50 percent) patients with moderate restriction, and 2 of 4 (50 percent) patients with severe restriction. Increased RV wall thickness (> 0.5 cm) was observed in 0 of 10 (0 percent) patients with mild restrictive impairment, 3 of 12 (25 percent) with moderate impairment, and 1 of 4 (25 percent) with severe restrictive impairment. Doppler evidence of pulmonary hypertension (ACT/ET ratio < 0.32) (ACT = acceleration time, ET = ejection time) was shown in 0 of 10 (0 percent) patients with a mild restrictive impairment, 8 of 12 (66 percent) patients with moderate restriction, and 4 of 4 (100 percent) patients with severe restriction (p < 0.01 mild vs moderate and mild vs severe). The RV area by 2-D echocardiography correlated well with the FVC percent predicted (r = 0.90, p < 0.001). The ACT/ET ratio also correlated well with the FVC percent predicted (r = 0.73, p < 0.001). In conclusion, RV enlargement and pulmonary hypertension were seen only in patients with a moderate or severe restrictive ventilatory impairment. These data may be useful in the assessment of the likelihood of subtle RV enlargement in patients with occupational pleuropulmonary disease. PMID- 7988180 TI - Potassium and magnesium distribution, ECG changes, and ventricular ectopic beats during beta 2-adrenergic stimulation with terbutaline in healthy subjects. AB - OBJECTIVE: To study the effect of intravenous (i.v.) terbutaline on potassium (K) and magnesium (Mg) distribution, ECG changes, and prevalence of ventricular ectopic beats in healthy subjects. DESIGN: Randomized double-blind, placebo controlled crossover. Subjects received either placebo or terbutaline (bolus, 0.25 mg; maintenance dose, 5 micrograms/min). SETTING: University Department of Clinical Chemistry. PARTICIPANTS: Ten healthy male volunteers. Mean age was 24.1 (range, 20 to 31) years. MAIN OUTCOME MEASURES: Serum potassium and magnesium muscle potassium and magnesium, and muscle sodium-potassium pump number. Urinary excretion of potassium and magnesium. ECG changes (T-wave and QTC interval) and the number of ventricular ectopic beats. MAIN RESULTS: Terbutaline produced an immediate decrease in serum potassium level from 4.17 (4.04 to 4.30) mmol/L to a nadir of 3.32 (3.06 to 3.58) mmol/L (p < 0.001). The urinary excretion of potassium decreased from 0.077 mmol/min (0.052 to 0.102) to 0.038 mmol/min (0.025 to 0.051) (p < 0.01). There was an increase in the number of sodium potassium pumps from 1,104.1 nmol/kg dry weight (1,030.6 to 1,177.5) to 1,273.3 nmol/kg dry weight (1,193.5 to 1,353.2) (p < 0.01), but no measurable change in muscle potassium. The QTC interval increased from 395 (385 to 405)ms to 449 (432 to 466) ms (p < 0.003). There was no change in the number of ventricular ectopic beats. CONCLUSIONS: Short-term i.v. administration of terbutaline produced hypokalemia partly due to an increase in the number of sodium-potassium pumps. Furthermore, terbutaline induced changes in ECG with a highly significant lengthening of the QTc interval but with an unchanged number of ventricular ectopic beats in healthy subjects. PMID- 7988181 TI - Hemodynamic, respiratory, and metabolic effects of medium-chain triglyceride enriched lipid emulsions following valvular heart surgery. AB - STUDY: A lipid emulsion containing 10 percent medium-chain triglycerides (MCT) and 10 percent long-chain triglycerides (LCT) was infused at a rate of 1 ml/kg/h (3.3 mg/kg/min) for 2 h, in 12 patients (2 males, 10 females; mean age, 54 +/- 3 (SEM) years; range, 34 to 67 years) 24 h after open-heart surgery (mitral valve replacement). METHODS: Hemodynamic factors (pulmonary and radial artery indwelling catheters), oxygen and carbon dioxide partial pressures, oxygen saturation, oxygen delivery and consumption, and intrapulmonary shunt fraction were obtained before, during, and after lipid infusion (for 2 h), at 30-s intervals, along with some metabolic indexes (triglycerides, free fatty acids, glucose, insulin, lactate, acetoacetate). RESULTS: No statistically significant changes in heart rate, cardiac index, systemic and pulmonary pressures and resistances, central venous and pulmonary capillary pressures, or arterial oxygen partial pressure were observed during infusion. Arterial carbon dioxide partial pressure values were constantly reduced throughout and after the end of lipid infusion, as compared with baseline values, while oxygen consumption was increased significantly without any change in oxygen delivery. No adverse effects on intrapulmonary shunt fraction were observed. Statistically significant increases of triglycerides, free fatty acids, acetoacetate and insulin (peak values at end of the lipid infusion) were found in comparison with baseline values. Plasma glucose increased significantly during lipid infusion and remained higher than baseline values until the end of the study. Lactate levels were unchanged except for a slight decrease at the end of the study, without any derangement of acid-base equilibrium. Neither arrhythmias nor adverse clinical reactions were observed as a consequence of lipid infusion. CONCLUSIONS: Fat emulsions containing both MCT and LCT, when given at 3.3 mg/kg/min for 120 min following valvular heart surgery, do not exert negative cardiopulmonary effects, and could represent a source of rapidly metabolized substrates. PMID- 7988182 TI - Thoracocardiographic-derived left ventricular systolic time intervals. AB - Thoracocardiography noninvasively estimates left ventricular performance by recording ventricular volume curves with inductive plethysmography. We studied timing of these curves to evaluate their potential to accurately track systolic time intervals in comparison with standard methods. Thoracocardiographic left ventricular volume curves, carotid pressure pulses determined by applanation tonometry, the phonocardiogram and ECG were recorded simultaneously in ten normal subjects at various body positions achieved with a tilt table. An equation was derived to predict preejection period from onset of ejection in thoracocardiographic curves. Ventricular ejection time was calculated as total electromechanical systole obtained by phonocardiography minus preejection period. The equation was validated prospectively in 31 measurements in critically ill patients. In normal subjects, the interval ECG Q wave to ejection onset in thoracocardiographic curves correlated well with preejection period from applanation tonometry and phonocardiography (r = 0.92; standard error of estimate (SEE), 8 ms; p < 0.001). Thoracocardiographic curves showed a delay that varied with body position according to the regression equation: delay = 40 ms + 10 x sine (tilt angle) (where r = 0.62; SEE, 7 ms; p < 0.001). Application of this equation in the prospective study in patients revealed close agreement in systolic time intervals from thoracocardiography and simultaneous applanation tonometry plus phonocardiography, respectively. The mean difference +/- SD between methods in preejection periods was 3 +/- 7 ms and in the ratios of preejection period to left ventricular ejection time, 0.02 +/- 0.05. Trends of changes in systolic time intervals were identical for the two methods. We conclude that thoracocardiography combined with phonocardiography provides accurate systolic time intervals when corrected for a position-dependent delay of its waveforms. PMID- 7988183 TI - Myocardial sarcoidosis. Clinical value of technetium-99m sestamibi tomoscintigraphy. AB - STUDY OBJECTIVE: The presence of defects on rest thallium 201 myocardial scintigraphy, reversible after dipyridamole infusion, was already demonstrated in myocardial localization of sarcoidosis. The present study compared the respective efficiency of a new tracer of myocardial blood flow, 99mTc sestamibi (sestamibi), vs thallium 201 (TI) for the diagnosis and follow-up of myocardial sarcoidosis. METHODS: Quantitative single photon emission computed tomography (SPECT) was performed in 37 consecutive patients with confirmed sarcoidosis and clinical suspicion of myocardial localization. Three successive scans were performed in all patients within the same day: rest TI SPECT, rest sestamibi SPECT, and dipyridamole sestamibi SPECT. Thirteen patients were reinvestigated after 3 months of corticosteroid therapy. The size and intensity of the defects were compared using a computerized quantitative analysis of bull's eye. RESULTS: At rest, sestamibi SPECT is more sensitive than TI, demonstrating significantly larger defects (28.1 +/- 13.2% vs 17.2 +/- 12.8% of bull's eye area, p < 0.001) and detecting abnormalities in seven more patients (24 vs 17). All patients with abnormal TI scans also had sestamibi abnormalities. After dipyridamole infusion, sestamibi defects decreased significantly (28.1 +/- 13.2% vs 15.2 +/- 12.3%, p < 0.001). This improvement correlated with the evolution of sestamibi SPECT performed in the 13 patients reinvestigated after corticosteroid therapy (r = 0.85, p < 0.001). CONCLUSIONS: We conclude that sestamibi SPECT is suitable for the diagnosis of myocardial sarcoidosis and represents an objective tool for the follow-up. The improvement after vasodilatation supports the hypothesis of reversible abnormalities in most of these patients and accurately predicts corticosteroid efficiency. PMID- 7988184 TI - Intra-aortic balloon counterpulsation as a 'bridge' to cardiac transplantation. Effects in nonischemic and ischemic cardiomyopathy. AB - Intra-aortic balloon (IAB) counterpulsation has been utilized as an effective "bridge" to transplantation in patients with end-stage heart failure. To determine if patients with heart failure with nonischemic cardiomyopathy (NICM) derive the same benefit from IAB support as those with ischemic cardiomyopathy (ISCM), we evaluated 27 patients with NICM and 16 patients with ISCM who required IAB support while awaiting transplantation. Hemodynamic changes, effects on organ function (renal and hepatic), frequency of complications, and clinical outcomes were analyzed. Baseline demographics and hemodynamics were comparable in both groups (p = NS). Hemodynamics improved in both groups, immediately (15 to 30 min) following IAB insertion, with greater improvement (p < 0.05) in cardiac index and a trend toward greater reduction in filling pressures in the NICM group. Systemic vascular resistance fell to a similar degree in both groups. During continued IAB support (0.13 to 38 days in NICM, 1 to 54 days in ISCM), all hemodynamic changes persisted in both groups, with larger decrease (p < 0.05) in systemic vascular resistance and greater increase (p < 0.05) in cardiac index in the patients with NICM. The reduction in filling pressures, however, tended to be greater in patients with ISCM. Renal and hepatic function parameters improved to a similar extent in both groups. The frequency of complications and clinical outcome during IAB support were also similar in the two groups. These data confirm that IAB counterpulsation is a safe and effective "bridge" in patients with both NICM and ISCM with end-stage heart failure. The mechanism of sustained benefit in the two groups, however, may be different; afterload reduction appears to be more important in patients with NICM whereas reduction in filling pressures (increased coronary perfusion pressure) may be the main mechanism in patients with ISCM. PMID- 7988185 TI - Prevalence of sleep-disordered breathing in patients on a heart transplant waiting list. AB - We investigated the prevalence of sleep-disordered breathing in 20 outpatients on a heart transplant waiting list. All were younger than 60 years and had severe stable cardiac failure with a cardiac index below 2.5 L/min/m2 and a left ventricular ejection fraction below 25%. Nine patients (45%) exhibited ten or more apneas and hypopneas per hour of sleep (apneic group). In all patients but one, apneas and hypopneas were predominantly of the central type and occurred during Cheyne-Stokes respiration. There were no statistically significant differences between the apneic and nonapneic groups of patients in terms of age (51 +/- 5 years vs 49 +/- 11), body mass index (24 +/- 4 kg/m2 vs 22 +/- 3), cardiac index (1.87 +/- 0.35 L/min/m2 vs 1.84 +/- 0.40), isotopic left ventricular ejection fraction (13 +/- 5 vs 12 +/- 3%), arterial blood gas, or pulmonary function tests. Hypnogram characteristics showed poorer sleep quality in the apneic group than in the nonapneic group, with a larger number of arousals; this difference was found both for arousals lasting more than 30 s (8 +/- 5/h vs 4 +/- 2) and for arousals lasting less than 30 s (18 +/- 16/h vs 5 +/- 6) and was associated with increased wakefulness after sleep onset in the apneic group (138 +/- 82 min vs 84 +/- 45). Arousals were strongly associated with hyperpneic phases of Cheyne-Stokes respiration. We conclude that sleep-disordered breathing is common in patients with end-stage heart disease and adversely affects the quality of sleep. PMID- 7988186 TI - Changes in obstructive sleep apnea characteristics through the night. AB - It was our impression that the respiratory parameters in obstructive sleep apnea (OSA) worsened as the night progressed. To confirm this, we review polysomnographic studies from 66 patients with apnea-hypopnea indices (AHI) of 40 to 125 events per hour, dividing bed time into equal quartiles. As the night progressed, the mean apnea duration (MAD) increased from 27.2 s to 34.6 s (p < 0.0001), mainly from increases during NREM sleep. The proportion of time spent in apnea increased from 54 to 71% (p < 0.0001) due to increases in both MAD and the proportion of REM sleep (from 2.8 to 14.7% of the total sleep time). The AHI did not change significantly between quartiles. Even though preapneic oxygen saturation did not change and apnea duration increased as the night progressed, the end-apneic saturation did not decrease, hence the rate of oxygen desaturation decreased. Also, it was found that patients with an AHI greater than 65 events per hour increased their proportion of time spent in apnea significantly more than those with an AHI smaller than 65, as the night progressed. In the patients with an AHI greater than 85, this was due to both an increase in MAD and AHI. In conclusion, in patients with an AHI greater than 40 events per hour, the severity of apnea increased as the night progressed due to lengthening of MAD, increased proportion of REM sleep, and in the most severe patients, also an increase in AHI. Even though the exact pathophysiologic mechanisms for the observed changes are unknown, a decrease in respiratory muscle effort with consequent decrease in oxygen consumption may explain both the lengthening of the apneas and the decrease in the rate of oxygen desaturation. PMID- 7988187 TI - Recurrence of sleep apnea without concomitant weight increase 7.5 years after weight reduction surgery. AB - In this study we report on a long-term follow-up of 14 morbidly obese sleep apneic patients, 11 of whom were male and 3 female. The mean age was 46 +/- 8.5 years. These patients had undergone weight reduction surgery. Before surgery, body mass index (BMI) and apnea index (AI) were 45 +/- 7.2 kg/m2 and 40 +/- 28.8 (SD) h-1, respectively. Four and a half months after surgery (range, 2 to 7 months), both BMI and AI significantly decreased to 33 +/- 7.5 kg/m2 and 11 +/- 16.4 h-1, respectively. Seven and half years after surgery (range, 5 to 10 years), BMI increased only slightly to 35 +/- 6.0 kg/m2 (p > 0.2), while AI increased significantly to 24 +/- 23 h-1 (p < 0.05). There were poor and insignificant correlations between changes in BMI and AI prior to 4.5 months after operation (r = 0.23; p > 0.4). and 4.5 months to 7.5 years after operation (r = 0.41; p > 0.1). We conclude that morbid obesity is not the only causative factor in the sleep apnea syndrome for these patients. Weight reduction surgery alone does not "cure" their sleep apnea, and they are still at risk. PMID- 7988188 TI - Sleep and nocturnal mouthpiece IPPV efficiency in postpoliomyelitis ventilator users. AB - STUDY OBJECTIVE: Intermittent positive pressure ventilation (IPPV) can be delivered via various oral, nasal, or oronasal interfaces as an alternative to tracheostomy for up to 24 h of ventilatory support. Nocturnal nasal IPPV is often associated with frequent transient but at times severe oxyhemoglobin desaturations (dSaO2s) and sleep fragmentation. The purpose of this study was to determine if nocturnal mouthpiece IPPV is also associated with dSaO2s and sleep disruption. DESIGN: Twenty-seven postpolio ventilator-assisted individuals (VAIs) using mouthpiece IPPV with little or no ventilator-free breathing time (VFBT) underwent nocturnal oxyhemoglobin saturation (SaO2) monitoring. In addition, 15 underwent nocturnal capnography and 13 underwent polysomnography. RESULTS: Mean nocturnal SaO2 was normal in 22 of 27 and maximum end-tidal PCO2 was normal in 12 of 15 VAIs. Use of lipseal retention for nocturnal mouthpiece IPPV significantly improved blood gas values during sleep. The polysomnography results demonstrated relatively normal sleep efficiency. CONCLUSIONS: Nocturnal mouthpiece IPPV is most effective with lipseal retention. It can provide normal alveolar ventilation and SaO2 during sleep for VAIs with little or no measurable vital capacity or VFBT. Because transient dSaO2s can be eliminated with lipseal retention, it may disrupt sleep less than nasal IPPV. PMID- 7988189 TI - Heart rate variability during sleep in infants with bronchopulmonary dysplasia. Effects of mild decrease in oxygen saturation. AB - We sought to determine whether abnormal heart rate modulation by the autonomic nervous system occurs in patients with severe bronchopulmonary dysplasia (BPD) in relation to sleep stages and mild changes in arterial oxygen saturation SaO2. On 10 oxygen-dependent 7- to 29-month-old infants with BPD, polygraphic recordings, including heart and respiratory rate and body movement detection, were performed. Heart rate variability was evaluated in high (HF), mid, and low (LF) frequency bands. Parameters were analyzed in two ranges of SaO2: normal range, (SaO2 greater than 95%), and mild decrease in (SaO2, values of 90 to 94%). In contrast to what is normally observed, LF at normal SaO2 was less marked in rapid eye movement, (REM) sleep than in non-rapid eye movement (NREM) sleep stage 2. A mild decrease in SaO2, as compared with a normal SaO2 value, was associated with: (1) a heart and respiratory rate acceleration, (2) a decrease in HF in REM sleep (p < 0.02); (3) an increase in LF in NREM sleep stage 2 (p < 0.02), intensifying the change observed in a normal SaO2 level. These data show that a mild decrease in SaO2 increases modifications of autonomic control observed in infants with severe BPD. PMID- 7988190 TI - Benefits of nocturnal nasal CPAP in patients with cystic fibrosis. AB - Patients with cystic fibrosis (CF) often hypoventilate during sleep with marked falls in oxygen saturation (SaO2%). This occurs most commonly during REM sleep, when there is a reduction in rib cage excursion and a fall in end-expiratory lung volume (EELV). The aim of this study was to examine the effect of nocturnal nasal continuous positive airway pressure (nCPAP) on SaO2 and the respiratory disturbance index (RDI) during sleep in patients with CF and severe lung disease. Seven patients (FEV1% pred, 23 +/- 5; range, 14 to 28%) were evaluated during sleep on two nights, control and nCPAP (11 +/- 2 cm H2O; range, 8 to 16 cm H2O), with four patients breathing room air and three patients breathing supplemental oxygen on both nights. Mean awake SaO2 was 91 +/- 1% (range, 89 to 93%). All patients showed significant oxyhemoglobin desaturation and respiratory disturbance in the control study. The maximal falls in SaO2 (15 +/- 10%) were most often associated with phasic eye movements, and a decline in rib cage excursion and the sum signal (Respitrace) during REM sleep. Nasal CPAP resulted in a significant improvement in the mean minimum oxygen saturation (MMOS) during both NREM (nCPAP 91 +/- 3% vs control 88 +/- 2%, p < 0.05) and REM sleep (nCPAP 89 +/- 6% vs control 83 +/- 6%, p < 0.05). Transcutaneous CO2 measurements were not significantly different between the control and the nCPAP studies. The RDI was also significantly reduced with nCPAP especially during REM sleep (9 +/- 7 events per hour vs control 25 +/- 11 events per hour, p < 0.05). Nasal CPAP caused no change in total sleep time or sleep efficiency yet significantly reduced the RDI and improved baseline SaO2 during both NREM and REM sleep. PMID- 7988191 TI - Exercise echocardiographic correlates of transient dilatation of the left ventricular cavity on exercise thallium-201 SPECT imaging. AB - Transient dilatation of the left ventricular cavity on exercise thallium perfusion imaging is recognized as a marker of significant coronary disease, but the mechanisms that produce this finding are not fully understood. We studied 32 patients who underwent exercise thallium imaging and exercise echocardiography to determine the changes in left ventricular cavity size that underlie transient dilatation. Left ventricular area from the apical four-chamber view was used to approximate left ventricular cavity size. There were 24 patients who did not have transient dilatation (group 1) and 8 patients who did have transient dilatation (group 2) on thallium imaging. Systolic area decreased from rest to exercise in group 1 patients but not in group 2 patients. There was no significant change in diastolic area from rest to exercise in either group 1 or group 2 patients. Thus, exercise-induced systolic dysfunction, manifested as a failure to decrease left ventricular systolic cavity size in exercise, may be an important mechanism in producing scintigraphic transient dilatation. PMID- 7988192 TI - Differing effects of airway obstruction on physical work capacity and ventilation in men and women with COPD. AB - BACKGROUND: Although the natural history of COPD is thought to be well known, studies assessing differences in the onset and course of the disease by gender are surprisingly lacking. This study is a cross-sectional analysis using progressive cycle ergometry exercise testing to assess male and female patients at specific levels of airway obstruction to see if they differ in their exercise capacity and decline in functional capacity. METHODS: The study group included 417 patients with COPD, 55 to 85 years of age, who were compared with 29 controls of similar age; all patients had COPD (FEV1/FVC < 75% predicted) without restrictive disease. Exercise testing in groups based on the level of pulmonary dysfunction defined by FEV1/FVC ratios (mild, 60.5 to 69.5%; moderate, 50.5 to 60.5%; severe < 50.5%) was analyzed. Data were evaluated using the Statistical Analysis System, analyzing gender and degree of airway obstruction and adjusting for any difference in age and peak exercise heart rate (covariate analysis of variance). RESULTS: Men demonstrated progressive reductions of body weight, exercise ability (assessed by the VO2), oxygen pulse (O2P, an indicator of stroke volume), and maximum exercise ventilation (VEmax) even with mild pulmonary dysfunction. Women did not lose weight, and maintained usual exercise ability (VO2, VEmax) and O2P until moderate or severe disease was present. Additional confirmation of a decrease in cardiac function for men with mild airway obstruction (p < 0.0001, controls), but not for women with mild airway disease, was obtained by estimation of cardiac output. Further, women presented with COPD at lower levels of tobacco smoke exposure than men for the entire group (43.8 vs 63.0 pack-years, p < 0.0001) and for each subgroup of disease severity. There were proportionally more life-time female nonsmokers than male nonsmokers with COPD (16 vs 5, p < 0.001). CONCLUSIONS: Male and female patients with COPD differed in their decline of functional aerobic capacity even at equivalent levels of pulmonary dysfunction. One reason for this appeared to be a decrease in the O2P occurring early in the natural history of the disease in the men and not in the women. Although general body de-conditioning may be the cause, heart disease may also be a contributing aspect. The relative delay in the loss of exercise capacity and body mass by the women may relate to predisease differences in physical activity. Women manifested significant lung disease with less cigarette smoking than men. This may be attributable to a different susceptibility to cigarette smoke between the sexes. These results suggest that there appear to be differences in the natural history of COPD in men and women. PMID- 7988193 TI - Oxitropium bromide improves exercise performance in patients with COPD. AB - Inhaled anticholinergics may be the first-line therapy for stable COPD. However, the effect of inhaled anticholinergic agents on exercise capacity is still controversial. Fourteen patients with stable COPD (age, 64.6 +/- 5.9 years) completed a randomized, double-blind placebo-controlled crossover trial. All the patients were studied by symptom-limited progressive cycle ergometry before and 90 min after the inhalation of either oxitropium bromide, 800 micrograms, or an identical placebo. Spirometry was assessed before and after each exercise test. While FEV1 averaged 0.85 +/- 0.34 L at 90 min after the inhalation of placebo, FEV1 was 1.01 +/- 0.41 L at 90 min after the inhalation of oxitropium, 800 micrograms (significant from placebo, p < 0.001). The maximal workload of 94.0 +/ 25.8 W after oxitropium administration was significantly greater than the 87.6 +/- 24.7 W measured after placebo (p < 0.01). The maximal minute ventilation was 40.2 +/- 12.3 L/min after oxitropium inhalation and 36.8 +/- 10.5 after placebo inhalation (p < 0.05). The differences in maximal oxygen consumption, maximal carbon dioxide production, and maximal heart rate between oxitropium and placebo inhalation also were statistically significant (p < 0.05, p < 0.05, and p < 0.01, respectively). There was a significant correlation between the change in maximal workload and the change in FEV1 before and after inhalation (r = 0.625, p < 0.01). The inhalation of oxitropium bromide, 800 micrograms, can improve the exercise capacity of patients with stable COPD. It is suggested that the effect is due to the bronchodilation induced by this drug. PMID- 7988194 TI - Maximal exercise tolerance in chronic congestive heart failure. Relationship to resting left ventricular function. AB - The relationship between maximal exercise tolerance and resting radionuclide indexes of left ventricular systolic and diastolic function were evaluated in 20 ischemic and 44 idiopathic cardiomyopathy patients with New York Heart Association class 2-4 chronic congestive heart failure. Left ventricular ejection fraction, peak systolic ejection rate, peak diastolic filling rate, time to peak filling from end-systolic volume, and fractional filling in early diastole were measured from the radionuclide ventriculogram. All patients underwent symptom limited exercise testing with on-line measurement of oxygen consumption. In the ischemic group, all of the radionuclide indexes correlated poorly with maximal exercise oxygen consumption (VO2max) except the peak systolic ejection rate which correlated modestly (r = 0.58, p < 0.05). Peak systolic ejection rate was significantly lower (p < 0.01) as were the peak diastolic filling rate and fractional filling in the first third of diastole (p < 0.05) in ischemic patients with marked exercise intolerance (VO2max < or = 14 mL/kg/min) compared with those with preserved exercise tolerance (VO2max > 14 mL/kg/min). In the idiopathic group, none of the radionuclide indexes correlated well with VO2max; and all indexes were similar in patients with and without marked exercise intolerance. These data suggest that (1) resting left ventricular ejection fraction poorly predicts maximal exercise capacity in both ischemic and idiopathic cardiomyopathy and (2) resting peak systolic ejection rate, peak diastolic filling rate, and fractional filling in early diastole may predict exercise tolerance in ischemic but not idiopathic cardiomyopathy. PMID- 7988195 TI - Comparison of Ballard catheter bronchoalveolar lavage with bronchoscopic bronchoalveolar lavage. AB - BACKGROUND: Bronchoscopic bronchoalveolar lavage (BAL) in mechanically ventilated patients requires a large endotracheal tube, physician expertise, expensive equipment, and support staff. METHODS: The Ballard BAL catheter is a disposable coude tip 16F device that can be attached to the endotracheal tube and ventilator circuit without loss of positive end-expiratory pressure (PEEP) and also allows supplemental delivery of oxygen between the 12F inner and outer catheters. The catheter is directed into the selected bronchus. The inner catheter with mushroom tip is then advanced until it wedges by feel. Thirteen patients at a tertiary care, university hospital, had BAL performed through both the bronchoscope and Ballard BAL catheter using five aliquots of 20 mL of normal saline solution each. The return was quantified and submitted for blinded, paired laboratory investigations, including Gram stain and quantitative culture, and special stains and cultures as clinically appropriate. RESULTS: The procedure was well tolerated in all patients with no difference between devices in oxygen saturations; however, air leaks occurred in patients undergoing bronchoscopy and compromised safety in one. Two patients required reintubation to facilitate passage of the bronchoscope. The bronchoscopic BAL return averaged 49 mL (range, 5 to 85 mL) while BAL catheter averaged 37 mL (range, 18 to 70 mL) both being sufficient for all desired investigations except one patient who had undergone bronchoscopy. All were of excellent quality based on microscopy. The BAL results were concordant in nine patients: two Pneumocystis carinii, one Candida, one Streptococcus agalactiae, one Streptococcus pneumoniae, and no infection in four. Diagnoses of tuberculosis and Enterococcus (confirmed by blood culture) were obtained by the Ballard BAL catheter only. Kaposi's sarcoma and metastatic histiosarcoma were visualized by bronchoscope only. Two patients had compassionate plea use of the Ballard BAL catheter because of a small endotracheal tube. Hemorrhage secondary to lupus was documented in one and nosocomial infection was excluded in the other. CONCLUSIONS: The Ballard BAL catheter allows easy, safe BAL, without loss of diagnostic yield, when visualization is not required in mechanically ventilated patients. The Ballard BAL catheter allows maintenance of PEEP when used with the supplied adapter and can be used with small endotracheal tubes. PMID- 7988196 TI - Bronchoalveolar lavage neutrophilia in asthmatic and healthy volunteers after controlled exposure to ozone and filtered purified air. AB - STUDY OBJECTIVE: To characterize the pulmonary response of asthmatic and healthy nonsmoking adult men to 0.20 ppm ozone by controlled chamber exposure. DESIGN: A prospective, crossover study of five atopic asthmatic and five normal subjects randomly exposed to ozone and filtered purified air (FPA) for 6 h, consisting of 30-min alternating periods of rest and moderate exercise. The two exposures were separated by at least 30 days. SETTING: A controlled exposure in a stainless steel chamber. PATIENTS: Five atopic asthmatic and five normal subjects between 18 and 45 years of age. Treatment with medications was withheld from asthmatics prior to the exposures. All subjects were nonsmokers. INTERVENTIONS: Symptoms were assessed throughout the exposures. Pulmonary function was measured at baseline, hourly throughout an exposure, and after an exposure. Bronchoalveolar lavage (BAL) was performed 18 h after the completion of an exposure. The BAL fluid (BALF) was analyzed for cell count and differential; the cell-free supernatant was analyzed for albumin, tumor necrosis factor (TNF), interleukin 1 (IL-1), interleukin 6 (IL-6), and interleukin 8 (IL-8). RESULTS: There were statistically significant increases in IL-8 levels, as well as percent polymorphonuclear neutrophils (PMNs) and PMNs per milliliter of lavage in asthmatics exposed to ozone as compared with the same asthmatics exposed to FPA and the same normal subjects exposed to ozone and FPA. Interleukin 6 was also significantly increased in asthmatics exposed to ozone. The BALF albumin, TNF, and IL-1 levels were not significantly different among the four groups. There were no differences between asthmatics and healthy controls exposed to ozone or FPA in baseline to postexposure FEV1, FVC, FEV1/FVC, and sRaw. CONCLUSIONS: We conclude that asthmatics exposed to ozone develop a significant BALF neutrophilia and increased levels of the cytokines, IL-8 and IL-6. These BALF findings occur even though the level of ozone exposure was not significant enough to reduce pulmonary function. PMID- 7988197 TI - Elevated surfactant protein A in bronchoalveolar lavage fluids from sarcoidosis and hypersensitivity pneumonitis patients. AB - Interstitial lung diseases often are accompanied by histopathologic evidence of alveolar type 2 cell alterations. In the alveolar milieu, the surfactant-specific protein A (SP-A) is a secretory product of alveolar type 2 cells. Therefore, we measured SP-A levels in bronchoalveolar lavage (BAL) fluids from patients with untreated sarcoidosis (n = 35) and hypersensitivity pneumonitis (HP [n = 10]) and compared the results with those from 21 healthy control subjects. In sarcoidosis patients, SP-A was markedly higher than in control subjects with a mean of 8.0 micrograms/ml of recovered BAL fluid +/- 0.7 SEM (p < 0.0001 compared with control subjects). In HP, SP-A values were comparable with those in sarcoidosis with a mean of 9.0 micrograms/ml +/- 1.7 SEM. Mean SP-A in the control group was 4.0 micrograms/ml +/- 0.3 SEM. These results suggest that SP-A secretion is stimulated in sarcoidosis and HP. Further studies seem justified to investigate the role of the surfactant system in interstitial lung diseases as well as the potential clinical usefulness of SP-A measurements in BAL. PMID- 7988198 TI - Intrapleural talc for the prevention of recurrence in benign or undiagnosed pleural effusions. AB - Chemical pleurodesis has become the preferred treatment for definitive management of malignant pleural effusions. The treatment of patients with recurrent benign or undiagnosed pleural effusions, however, remains a difficult clinical problem. Tetracycline has been widely used as a sclerosing agent, but parenteral tetracycline is no longer available. Therefore, alternative sclerosing agents are needed. Talc was used for the first time in 1935, and subsequently there have been several reports documenting its effectiveness in the treatment of malignant pleural effusion and pneumothorax. The objective of this study is to present our experience with a low dose of aerosolized talc for controlling nonmalignant pleural effusions. Between May 1985 and October 1992, twenty-two patients underwent talc pleurodesis at the time of thoracoscopy for control of a nonmalignant effusion. The cause of the effusion was cirrhosis in six patients, systemic lupus erythematosus in two, chylothorax in five, and no diagnosis in nine patients. Follow-up has ranged from 18 days to 5 years. Only two patients (9 percent), one with cirrhosis and another with an undiagnosed pleural effusion, had a recurrence of the effusions. We conclude that the intrapleural administration of 2 g of aerosolized talc is an effective treatment for recurrent benign (including chylothorax) or undiagnosed pleural effusions. PMID- 7988199 TI - Development of a disposable spray canister for talc pleurodesis. A preliminary report. AB - Talc pleurodesis has been used for more than 50 years in both the United States and in Europe, and it has proven to be safe and effective in patients with malignant pleural effusions as well as recurrent pneumothorax. In this preliminary report, we describe a disposable, single-use spray canister that allows intrapleural administration of sterile, asbestos-free Luzenac talc, thus facilitating thoracoscopic talc insufflation for pleurodesis, particularly in patients with recurrent malignant effusions. The talc is delivered ready to use, administered via a hollow plastic delivery catheter that can be inserted through the pleural trocars used during thoracoscopy. Use of this spray canister allows practitioners to avoid complex handling and sterilization procedures required for bulk talc powder. PMID- 7988200 TI - The bronchial response, but not the pulmonary response to inhaled methacholine is dependent on the aerosol deposition pattern. AB - The clinical effect of inhaled radio-labeled (Technetium-99m diethylenetriamine pentaacetic acid) methacholine was studied in two separate experiments performed in eight symptom-free asthmatics with bronchial hyperresponsiveness. Aerosols were formed by two different nebulizers, producing either mainly small aerosol particles (2-microns mass median aerodynamic diameter [MMAD]) for peripheral, or mainly large aerosol particles (9-microns MMAD) for large airway deposition. The intended site of deposition was confirmed by gamma camera recordings. Changes in specific airway conductance (sGaw) were set as an index of central airway constriction, and functional alterations in the gas exchanging parts of the lung were estimated by multiple inert gas elimination technique (MIGET) and arterial blood gas analyses. The main finding was that the responses, as measured by the changes in arterial blood gases and by MIGET, were similar in the two experiments, while the fall in sGaw was significantly larger after deposition in the main bronchi than in the peripheral airways (p < 0.05). The time courses of the abnormalities in the gas exchanging elements were much longer than those of the responses of the central airways, and the abnormalities were recorded still at the end of the experiment 2 h after challenge in most patients. A discrepancy in dose dependency and time courses suggests differences in mechanism and/or dynamics of the responses exerted by the various target organs. Interaction in the process of clearance from the lung of inhaled methacholine by the bronchial circulation may have contributed to the observed discrepancies. PMID- 7988201 TI - A comparison of commercial jet nebulizers. AB - Seventeen commercially available jet nebulizers from 15 commercial sources were studied (Acorn-I, Acorn-II, AquaTower, AVA-NEB, Cirrhus, Dart, DeVilbiss 646, Downdraft, Fan Jet, MB-5, Misty Neb, PARI LC JET, PARI-JET, Salter 8900, Sidestream, Updraft-II, Whisper Jet). All nebulizers were filled with 2 ml of saline solution plus 0.5 ml of albuterol and powered with the same source (DeVilbiss PulmoAide). We compared total output (TO), time for total output (TTO), and percent output in respirable range (PORR). The TO was obtained by weighing before nebulization and at the point of eight-fold decline in output. The TTO was calculated from initiation of nebulization to the point of eightfold decline in output. The PORR was measured by a laser particle analyzer in continuous nebulization to the same point of abrupt drop in output. The TO varied from 0.98 To 1.86 ml (p < 0.0001) with the Acorn-I, Acorn-II, Updraft-II, and Sidestream, significantly greater than the others (p < 0.05). The TTO varied from 2.28 to 20.95 min (p < 0.0001). The AquaTower, PARI LC JET and PARI-JET, DeVilbiss, and Dart were significantly shorter than the others (p < 0.05). The PORR varied from 21.89 to 71.95 percent (p < 0.0001). The Sidestream was significantly greater than all others (p < 0.05). The PARI LC JET and PARI-JET were, in turn, significantly greater than the remaining models (p < 0.05). To combine these characteristics, we calculated respirable particle delivery rate (RPDR) by dividing TO by TTO and multiplying by PORR. The RPDR varied from 0.03 ml/min to 0.26 ml/min (p < 0.0001). The PARI LC JET (0.24 ml/min) and the PARI JET (0.26 mg/min) had a RPDR that was significantly greater than the other models except the AquaTower, which, however, had a markedly variable performance. The Sidestream (0.19 mg/ml) did not differ significantly from the above group, nor from the DeVilbiss and Downdraft. All other models had significantly lower outputs (p < 0.05). We conclude that the output characteristics of commercial nebulizers vary greatly and will impact on the time required for treatment as well as the total amount of drug delivered to the lungs. PMID- 7988202 TI - Frequency and site of gastroesophageal reflux in patients with chest symptoms. Studies using proximal and distal pH monitoring. AB - Prolonged ambulatory pH monitoring was performed on 89 patients with previous diagnosis of asthma (27 patients), chronic cough (28 patients), noncardiac chest pain (34 patients), and on 27 healthy control subjects. The extent of gastroesophageal reflux (GER) was determined using a catheter containing two antimony pH electrodes positioned 5 cm and 20 cm above the superior border of the manometrically determined lower esophageal sphincter. Reflux was defined as a drop in pH to < 4 in the distal esophagus. We compared both pH < 4 and pH < 5 as the beginning of reflux episodes for the proximal esophagus. Considering the confidence interval of 95% in healthy control subjects as a normality criterion, we found a prevalence of abnormal distal GER in 44% of asthmatics, 50% of patients with cough, and 53.8% of patients with noncardiac chest pain. Abnormal proximal acid exposure was found in 24% of asthmatics, 10.7% of patients with cough and 44.1% of patients with chest pain. Distal acid exposure was significantly longer than proximal esophageal acid exposure in all patient groups (p < 0.05). There were no differences in the evaluation of proximal GER comparing pH < 4 with pH < 5. The data also indicate a tendency toward upright, rather than supine acid exposure. These results support the use of 24-h pH monitoring in patients with chest complaints and indicate that GER may frequently be involved in the pathogenesis. They do not support the theory that proximal GER is a specific etiologic factor in chronic cough or asthma. PMID- 7988203 TI - Survival analysis of untreated patients with non-small-cell lung cancer. AB - The survival rate analysis of 130 patients with non-small-cell lung cancer who did not receive any specific anticancer therapy showed no statistically significant differences in the survival rates between various TNM combinations classified into stage groups II, IIIa, IIIb, and IV, as proposed by Mountain in 1989 and adopted by the American Joint Committee on Cancer. Following these findings, based on survival probabilities, two distinctive staging groups could be distinguished. The first stage group was composed of only the T1, 2N0, M0 combination, and the second of all other TNM combinations. In a purely biologic sense of tumor growth, the lymph node involvement appeared to be the crucial factor determining the length of survival. PMID- 7988204 TI - Epigallocatechin gallate. The major causative agent of green tea-induced asthma. AB - We describe three patients who worked in green tea factories and developed asthmatic and nasal symptoms after exposure to green tea dust. To clarify what component(s) of green tea leaves might be responsible for causing asthma, we prepared catechins, the major components of green tea leaves. Epigallocatechin gallate (EGCg; MW: 458 daltons), a major catechin, was purified by high performance liquid chromatography. Subjects included three patients with green tea-induced asthma, five asthmatics with no previous exposure to tea dust, and five healthy controls. It was found that all three patients exhibited an immediate skin and bronchial response to EGCg. Prausnitz-Kustner test with EGCg was also positive. However, none of the asthmatic and healthy controls showed a positive reaction. These results indicate that EGCg is a causative agent of green tea-induced asthma and suggest that an IgE-mediated response is, at least in part, responsible for causing this type of occupational asthma. PMID- 7988205 TI - The composition of gas given by mouth-to-mouth ventilation during CPR. AB - STUDY OBJECTIVE: To compare the concentration of a rescuer's exhaled O2 and CO2 during mouth-to-mouth ventilation with or without chest compression. DESIGN: Prospective repeated measures study. Simulated one- and two-rescuer cardiopulmonary resuscitation (CPR) was performed as recommended by the American Heart Association. SETTING: University laboratory. PARTICIPANTS: Fifty-five healthcare professionals certified in basic and advanced cardiac life support volunteered as rescuers in this study. MEASUREMENTS AND RESULTS: Thirty-three volunteers performed one-rescuer CPR, and 22 volunteers performed two-rescuer CPR. Minute ventilation for both groups increased 50% to 130% during CPR (p < 0.05). During the performance of CPR, the concentration of exhaled O2 increased from 16.4 +/- 0.7% to 16.9 +/- 0.5% in the one-rescuer CPR group and from 16.5 +/ 0.9% to 17.8 +/- 0.6% in the two-rescuer CPR group (p < 0.05). The concentration of exhaled CO2 in the one-rescuer CPR group did not change significantly throughout the entire experiment, but decreased in the two-rescuer CPR group from a baseline measurement of 4.0 +/- 0.6% to 3.5 +/- 0.4% (p < 0.05). During CPR, the concentration of exhaled CO2 was 4.0 +/- 0.4% in the one-rescuer CPR group compared with 3.5 +/- 0.4% in the two-rescuer CPR group (p < 0.05). CONCLUSIONS: The gas given by mouth-to-mouth ventilation is a hypercarbic and hypoxic mixture compared with room air. Mouth-to-mouth ventilation is the only circumstance in which a hypercarbic and hypoxic gas is given as therapy. Further laboratory and clinical studies are necessary to determine the effect of mouth-to-mouth ventilation during CPR. PMID- 7988206 TI - Prognostic value of serum cholinesterase in organophosphate poisoning. AB - OBJECTIVE: To determine whether serum cholinesterase level has a prognostic value in human acute organophosphorus poisoning. DESIGN: Cohort (prospective) prognosis study. SETTING: Medical ICU at University Hospital. PATIENTS: Thirty consecutive patients admitted to the ICU for acute organophosphate poisoning. MEASUREMENTS: Serum cholinesterase level was measured in all patients at the time of hospital admission. Severity of intoxication was assessed by the total dose of atropine required to relieve poisoning manifestations, the Simplified Acute Physiology Score, the need for assisted ventilation, and by a specific grading system previously validated that identified two groups of patients: group 1 (low severity, n = 18) and group 2 (high severity, n = 12). RESULTS: Serum cholinesterase level did not correlate with the total dose of atropine or with the Simplified Acute Physiology Score. Mean serum cholinesterase level was not significantly different between group 1 and group 2 patients (448 +/- 409 U/L in group 1 compared with 611 +/- 575 U/L in group 2 (p = NS); it was also not significantly different between patients with and without mechanical ventilation support (567 +/- 571 vs 470 +/- 409, respectively). CONCLUSION: Serum cholinesterase levels have no prognostic value in acute organophosphate poisoning. Thus, a grading system to identify high-risk patients based on this measurement is most likely unreliable. PMID- 7988207 TI - Computed tomography in established adult respiratory distress syndrome. Correlation with lung injury score. AB - STUDY OBJECTIVES: To identify serial changes in the appearances of the lungs on computed tomography (CT) in patients with established adult respiratory distress syndrome (ARDS). Second, to evaluate any relationship between the extent of morphologic abnormalities on CT anatomic and physiologic derangement using a numeric score of the severity of lung injury. DESIGN: Retrospective, descriptive. SETTING: Adult intensive care unit, Department of Radiology, and outpatient department of a national tertiary referral center. PATIENTS: Eight patients meeting diagnostic criteria for ARDS able to tolerate CT scanning during the acute phase of their illness and who survived to be reevaluated during convalescence. INTERVENTIONS: Mechanical ventilatory support. Conventional intensive care support of other failed systems a appropriate. MEASUREMENTS AND RESULTS: Thin-section CT scans of the lungs categorized as to extent (calculated percent volume of abnormal lung), distribution, and dominant disease pattern. Concurrent lung injury score (LIS) was recorded at the time of the CT during the acute phase of illness (mean, 26 days; range, 3 to 48 days after precipitating event) and at follow-up (96; 17 to 187 days). On initial CT scans, disease patterns included ground-glass opacification (8/8), parenchymal distortion (8/8), multifocal areas of consolidation (6/8), reticular opacities (6/8), and linear opacities (5/8). On follow-up scans, there was clearing of consolidation in all patients, but ground-glass opacification persisted in four of eight patients. The reticular pattern persisted unchanged in five of eight patients, became more extensive in two of eight, and developed in one. A reticular pattern was most pronounced in areas that had been densely consolidated previously. Evidence of parenchymal distortion, present on the initial scan in all patients, persisted in six of eight patients. Computed tomographic features suggestive of emphysema developed in one patient. The LIS revealed moderate to severe ARDS in all patients initially; this decreased to a mild or zero LIS at follow-up. Overall, there was 76.9% +/- 5.3% abnormal lung on the initial CT scan and 34.5 +/- 9.3% on the follow-up CT scan. There was a significant correlation between the extent of abnormalities on CT and LIS (r = 0.75, p < 0.01). CONCLUSIONS: The CT appearances of patients with ARDS who survive are variable and relate to the pattern of disease in the acute phase. Furthermore, the extent of CT abnormalities correlates strongly with LIS in both the acute phase and at follow up. PMID- 7988208 TI - Determinants of outcome for patients in the medical intensive care unit requiring abdominal surgery: a prospective, single-center study. AB - OBJECTIVE: To identify objective factors, available at the time of surgical evaluation, associated with outcome for patients in the medical ICU undergoing abdominal surgery. DESIGN: Single-center, prospective observational study. SETTING: An academic tertiary care center. PATIENTS: The study included 1,617 consecutive patients in the medical ICU. INTERVENTION: Prospective patient surveillance and data collection. MEASUREMENTS: Patient demographics, severity of illness, organ system derangements, abdominal processes requiring surgery, and hospital mortality. RESULTS: Sixty-seven patients in the medical ICU (4.1 percent) developed an acute abdominal process potentially amenable to surgical intervention. Eleven of these patients (16.4 percent) elected not to undergo surgery (mortality = 100 percent). Forty-two of the 56 patients who underwent surgery survived (75.0 percent). Stepwise logistic regression analysis identified two independent objective predictors of mortality for this patient cohort (p < 0.05): an organ system failure index (OSFI) > 2 (adjusted odds ratio [AOR] = 19.5; 95 percent confidence interval [CI], 7.4 to 51.5; p < 0.001); and an APACHE II score > 18 (AOR = 9.4; CI = 3.1 to 28.3; p = 0.03). The observed mortality following surgery was stratified according to the presence or absence of these two factors: neither present, 5.1 percent; APACHE II > 18 present alone, 33 percent; OSFI > 2 present alone, 60 percent; and both present, 88.9 percent (p < 0.001). Surgical nonsurvivors and patients electing not to undergo surgery were similar without significant differences for demographics, severity of illness, or organ system derangements at the time of surgical evaluation. CONCLUSIONS: The number of organ system derangements and the severity of illness, as assessed by APACHE II, appear to be useful discriminators of outcome for patients in the medical ICU undergoing abdominal surgery. These data suggest potential outcome predictors for this selected group of patients in the ICU. PMID- 7988209 TI - Diagnostic accuracy and therapeutic impact of transthoracic and transesophageal echocardiography in mechanically ventilated patients in the ICU. AB - STUDY OBJECTIVES: To assess the respective diagnostic accuracy of transthoracic echocardiography (TTE) and transesophageal echocardiography (TEE) and their therapeutic implications in mechanically ventilated patients, in the intensive care unit (ICU). DESIGN: A prospective study. SETTINGS: Intensive care units of two tertiary referral teaching hospitals. PATIENTS: One hundred eleven ICU patients (81 men and 30 women; mean age 57 +/- 16 years). Fifty-seven percent were hospitalized for medical illnesses, 16.5 percent after thoracic surgery, 10.5 percent after other surgery, and 16.0 percent for multiple trauma. Their Simplified Acute Physiologic Score was 16 +/- 5. INTERVENTIONS: The echocardiograms were performed in order to solve well-defined clinical problems. TTE was the first step of the procedure and TEE was performed only when (1) TTE did not solve the clinical problems, and (2) TTE yielded unsuspected findings requiring TEE. During each echocardiographic study, the following were noted: ventilatory mode, clinical problems, imaging quality, results, consequence on acute care, duration of the procedure, and potential complications of TEE. Diagnostic accuracy was defined as the proportion of solved problems, and therapeutic impact was defined as changes on acute care that resulted directly from the procedure. MEASUREMENTS AND RESULTS: One hundred twenty-eight consecutive TTE and 96 TEE were performed. TTE solved 60 of 158 clinical problems (38 percent), whether positive end-expiratory pressure (> 4 cm H2O) was present or not (28 of 74 vs 32 of 84: p > 0.50). TTE allowed evaluation of left ventricular function in 77 percent of cases and pericardial effusion in every case, but it did not solve most of the other clinical problems. Indeed, the diagnostic accuracy of TEE was markedly superior (95/98 vs 60/158: p < 0.001), but TEE required a physician's presence longer (43 +/- 17 min vs 27 +/- 12 min: p < 0.001). When TTE and TEE were scheduled (n = 96), TEE yielded an additional diagnosis or excluded with more certitude a suspected diagnosis, except in two cases. TEE had a therapeutic impact more frequently than TTE (35/96 vs 20/128: p < 0.001). Cardiovascular surgery was prompted by echocardiographic findings in ten patients. TEE was well tolerated in all patients; there were no complications. CONCLUSIONS: TEE is a valuable well-tolerated imaging technique in mechanically ventilated patients. For the assessment of left ventricular systolic function and pericardial effusion; however, TTE continues to be an excellent diagnostic tool, even when positive end-expiratory pressure is present. Both TTE and TEE have a therapeutic impact in approximately 25 percent of cases. PMID- 7988210 TI - Partially and totally unloading respiratory muscles based on real-time measurements of work of breathing. A clinical approach. AB - OBJECTIVE: To evaluate the clinical feasibility of using real-time measurements of work of breathing obtained at the bedside with a portable, commercially available respiratory monitor as an objective and quantifiable guideline for appropriately setting pressure support ventilation (PSV) to partially and totally unload the respiratory muscles in patients with respiratory failure. DESIGN: In vivo measurements of work of breathing were performed on a consecutive series of patients after applying incremental levels of PSV. SETTING: University teaching hospital in a surgical ICU. PATIENTS: Thirty adults (18 men and 12 women, ages 20 to 77 years) who had acute respiratory failure were studied. All patients had an endotracheal or a tracheostomy tube in place and were breathing spontaneously, receiving continuous positive airway pressure and PSV. INTERVENTIONS: Intraesophageal pressure (indirect measurement of intrapleural pressure) was measured with an esophageal balloon catheter positioned in the mid- to lower third of the esophagus. Tidal volume was obtained by positioning a flow sensor between the "Y" piece of the breathing circuit and the endotracheal or tracheostomy tube. Airway pressure was measured from a catheter attached to the flow sensor. Data from these measurements were directed to the respiratory monitor (CP-100, Bicore Monitoring Systems) which calculates work of breathing performed by the patient using the Campbell diagram. Work of breathing performed by the ventilator to inflate the respiratory system was calculated by the monitor by integrating the change in airway pressure and tidal volume. Initially, the level of PSV was set to 0 cm H2O and work measurements were obtained. Pressure support ventilation was then increased until the work performed by the patient decreased to a range of 0.3 to 0.6 J/L, which corresponds to a normal range for physiologic work of breathing (ie, partial respiratory muscle unloading), and then until the work decreased to 0 J/L (ie, total respiratory muscle unloading). RESULTS: Work performed by the patient varied inversely (r = -0.83; p < 0.001) and work performed by the ventilator varied directly with the level of PSV (r = 0.94; p < 0.001). Work performed by the patient was 1.5 +/- 0.3 J/L at zero pressure support ventilation and decreased significantly to 0.50 +/- 0.1 J/L (p < 0.05) as the level of PSV was increased to 18 +/- 7 cm H2O. The respiratory muscles were partially unloaded under these conditions. Patient work decreased to 0 J/L and ventilator work increased when the muscles were totally unloaded at a PSV level of 31 +/- 8 cm H2O. CONCLUSION: We propose an objective and goal oriented clinical approach for using PSV by directly measuring the work of breathing performed by the patient with an easy to operate, bedside respiratory monitor and then applying pressure support ventilation to decrease the work to appropriate levels. Partially or totally shifting the workload from the respiratory muscles to the ventilator is appropriate under specific clinical conditions. PMID- 7988211 TI - Automatic weaning from mechanical ventilation using an adaptive lung ventilation controller. AB - STUDY OBJECTIVE: To evaluate a new method of closed-loop mechanical ventilation using an adaptive lung ventilation (ALV) controller in patients with different pathologic causes of respiratory failure at a time when they first met standard weaning criteria. STUDY DESIGN: Prospective, open, selected case study. SETTING: The 10-bed, multidisciplinary respiratory intensive care unit at Groote Schuur hospital, which is a teaching unit of the University of Cape Town. PATIENTS: Twenty-seven patients (9 patients in each of 3 groups: normal lungs, parenchymal lung disease, and COPD) who required prolonged mechanical ventilation and who met standard weaning criteria were included. Our institutional committee for ethical research approved the study and informed consent was obtained. INTERVENTIONS: The patients were mechanically ventilated and had daily measurements of vital capacity, respiratory rate, and arterial blood gas analysis until they met standard weaning criteria. On the day that each patient met the weaning criteria, a closed loop control algorithm providing ALV was implemented on a modified ventilator (Hamilton AMADEUS) with a PC-based lung function analyzer. After measuring gross alveolar ventilation, patients were placed in ALV and ventilatory and hemodynamic parameters were measured at baseline, 5 min, 30 min, and 2 h. Pertinent parameters measured included airway pressures, pressure support levels, respiratory rates, rapid shallow breathing indices, airway resistance indices, and patient respiratory drive and work indices. MEASUREMENTS AND RESULTS: In 22 patients, ALV reduced pressure support to 5 cm H2O and an intermittent mandatory ventilation rate of 4 breaths/min within 30 min, and all but 1 of these patients were successfully extubated within 24 h. In four patients, pressure support was maintained by ALV at a mean level of 14.6 cm H2O +/- for 2 h and these patients were recorded as having failed to wean. There was a measurable difference in an index of airway resistance relative to muscular activity between the successfully weaned and failed wean patients with COPD during the attempted wean by the ALV controller. CONCLUSIONS: ALV will provide a safe, efficient wean and will respond immediately to inadequate ventilation in patients when standard weaning criteria are met. PMID- 7988212 TI - Acute myocardial infarction. Reperfusion strategies. AB - Acute myocardial infarction is the result of an acute interruption of myocardial blood flow resulting in ischemic myocardial necrosis. The pathogenesis of this phenomenon nearly always involves acute thrombosis superimposed on a disrupted atherosclerotic plaque. Thrombolytic agents have been conclusively shown to reduce mortality in many patient subgroups with myocardial infarction, including the elderly, patients with inferior myocardial infarction, and patients with systolic hypertension. Nearly all patients with acute myocardial infarction of less than 6 h in duration with S-T segment elevation should receive thrombolysis unless significant contraindications exist and outweigh the potential benefits. Aspirin should be given to almost all patients regardless of whether they receive thrombolysis. Angioplasty and coronary artery bypass surgery are useful as primary or secondary modes of reperfusion in selected patients with infarction. PMID- 7988213 TI - An unusual cause of a right paratracheal mass. PMID- 7988214 TI - "Lost" tidal volumes in a 71-year-old ventilated patient. PMID- 7988215 TI - Chest physiotherapy and cystic fibrosis. Why is the most effective form of treatment still unclear? PMID- 7988216 TI - A problem of pulmonary edema developing postpartum. PMID- 7988217 TI - Extrapulmonary thoracic disease caused by Blastomyces dermatitidis. AB - A case of blastomycosis is reported involving the mediastinum and compromising the plexus brachialis. The pathology, pathophysiology, and treatment of this patient and of a previously reported patient are discussed and compared with the characteristics of extrapulmonary thoracic disease caused by histoplasmosis. Because of the favorable response of these patients to prolonged antifungal therapy, blastomycosis should be considered in the differential diagnosis of invasive extrapulmonary thoracic disease. PMID- 7988218 TI - Human papilloma virus associated with solitary squamous papilloma complicated by bronchiectasis and bronchial stenosis. AB - A 28-year-old man presented with recurrent pneumonias for 6 years. Chest radiograph and computed tomography showed localized bronchiectasis of the anterior segment of the left upper lobe. Bronchoscopy showed bronchial stenosis without an endobronchial lesion. After 6 weeks of antibiotic treatment, the patient had a recurrent pneumonia and underwent left upper lobectomy that showed a solitary squamous papilloma. In situ hybridization studies of the papilloma were reactive for human papilloma virus subtypes 6/11. PMID- 7988219 TI - Pulmonary mucormycosis presenting as an endobronchial lesion. AB - A 56-year-old diabetic man presented with left upper lobe collapse and postobstructive pneumonitis. Fiberoptic bronchoscopy revealed an endobronchial mass obstructing the left mainstem bronchus. The lesion resembled a bronchial adenoma; however, cytologic and histologic examination revealed invasive mucormycosis. The patient was treated with intravenous amphotericin B followed by endoscopic laser surgery that relieved the obstruction. PMID- 7988220 TI - Pulmonary hemorrhage. An uncommon cause of pulmonary infiltrates in patients with AIDS. AB - We describe two patients with AIDS who developed new diffuse pulmonary infiltrates during the course of their hospitalization. In both cases, the infiltrates were attributed to pulmonary hemorrhage complicating an existing condition rather than representing a new pulmonary process. Identification of pulmonary hemorrhage in these patients allowed for discontinuation of treatment with empiric medications and continued appropriate supportive care. PMID- 7988222 TI - Sudden enlargement of a deep cervical lymph node during and after treatment for pulmonary tuberculosis. AB - A 25-year-old Filipino woman presented with sudden massive enlargement of a deep cervical lymph node on two occasions: during adequate treatment of pulmonary tuberculosis and again 2 years after completion of therapy. Although this immunologic phenomenon is well known in childhood tuberculosis, occurrence in adults should also be recognized. PMID- 7988221 TI - Thoracic endometriosis. Recurrence following hysterectomy with bilateral salpingo oophorectomy and successful treatment with talc pleurodesis. AB - This is a report of an unusual patient who had four of the five manifestations of thoracic endometriosis, including right pneumothorax, left hemothorax, chest pain, and hemoptysis. This patient shows that recurrence of symptoms can occur while a patient is receiving hormonal replacement therapy even after hysterectomy and bilateral salpingo-oophorectomy; estrogen replacement should probably be delayed for several months to allow complete regression of the ectopic endometrial tissue. Alternatively, chemical pleurodesis can be effective in treating recurrent pneumothorax or hemothorax while the patient is receiving hormonal replacement. Bilateral pleural involvement and hemoptysis suggest microembolization of endometrial tissue as the pathogenic mechanism for thoracic endometriosis. PMID- 7988223 TI - Acquired laryngomalacia as a cause of obstructive sleep apnea. AB - We describe a patient who, 4 years after a radical neck dissection and radiotherapy, presented with obstructive sleep apnea; upon bronchoscopy, he was found to have acquired laryngomalacia. Inspiration induced upper airway obstruction due to a large flaccid epiglottis, large aryepiglottic folds, and edema of the supraglottic area. We suggest that acquired laryngomalacia can lead to obstructive sleep apnea. Patients with obstructive sleep apnea after radical neck dissection need to be evaluated for laryngomalacia with fiberoptic laryngobronchoscopy. Examination of the upper airway is useful to determine the nature and extent of any upper airway collapse. PMID- 7988224 TI - Radiofrequency ablation for the fast pathway of atrioventricular node reentry. Evidence for partial damage to the fast and lower common pathways. AB - Radiofrequency ablation was attempted in a 30-year-old woman with atrioventricular (AV) node reentry of the common variety. Energy was delivered to ablate a fast pathway. After energy delivery, the atrio-His interval prolonged following transient AV node block. Retrograde conduction was no longer present. However, dual AV nodal physiology and AV node reentry with similar retrograde atrial activation sequence could be shown post-ablation. These observations suggest that both fast and lower common pathways were partially damaged by ablation. PMID- 7988225 TI - Thoracoscopic lobectomy with mediastinal sampling in 80-year-old patients. AB - The purpose of this study was to determine whether thoracoscopy would allow standard lung cancer operations to be performed safely and completely in 80-year old patients. Elderly patients with lung cancer are usually offered compromise treatment (either radiation or wedge resection) for early-stage lung cancer because their operative risk for lobectomy or pneumonectomy is increased. This study consists of nine patients, 80 to 82 years of age, who underwent either lobectomy (eight cases) or left pneumonectomy (one case) with mediastinal node sampling by thoracoscopy. There were no deaths or major complications. Seven of the nine patients were discharged by the fifth postoperative day. The hospital stay was prolonged in two patients due to air leak or persistent chest tube drainage (11 and 13 days, respectively). The use of thoracoscopy does allow standard lung cancer treatment to be offered to selected elderly patients. PMID- 7988226 TI - Pneumomediastinum and bilateral pneumothoraces in a patient with hyperemesis gravidarum. AB - Hyperemesis gravidarum (HG) is a severe form of the more common nausea of early pregnancy. We report an unusual case of pneumomediastinum and bilatetral pneumothoraces presenting in the tenth week of pregnancy complicating HG. PMID- 7988227 TI - Fallibility of persistent blood return for confirmation of intravascular catheter placement in patients with hemorrhagic thoracic effusions. AB - Two patients are described with hemorrhagic thoracic effusions who required central venous catheterization. Presumed subclavian and internal jugular vein cannulation, ipsilateral to the hemorrhagic thoracic effusions, was confirmed by the operators in each case by the persistent aspiration of blood. Subsequent clinical and radiologic evaluation revealed that the vascular catheters were introduced into the pleural space. In both individuals, the persistent aspiration of extravascular hemorrhagic fluid mimicked intravascular catheter positioning. Physicians treating patients with hemorrhagic thoracic effusions need to be aware of this potential complication that can result in the delayed resuscitation of hemodynamically unstable patients. PMID- 7988228 TI - Mildly symptomatic pulmonary emboli associated with electrophysiologic procedures. Indications for anticoagulant use. AB - Symptomatic pulmonary emboli complicating electrophysiologic procedures are uncommon. Asymptomatic or mildly symptomatic embolic are likely much more common. This case report highlights the problem of extensive, but mildly symptomatic, pulmonary emboli occurring as a complication of electrophysiologic procedures, including catheter ablation. The role of anticoagulation during and following electrophysiologic procedures in preventing pulmonary emboli (which can have long term sequelae) is unknown. Currently, there appears to be no consensus regarding the use of anticoagulants either during or following electrophysiologic procedures, including those involving catheter ablation. Based on the presumed frequency and potential long-term complications of pulmonary emboli, anticoagulation during electrophysiologic procedures should be recommended. PMID- 7988229 TI - Pericarditis as the initial manifestation of inflammatory bowel disease. AB - Pericarditis is an uncommon extraintestinal manifestation of inflammatory bowel disease. Clinical presentations range from asymptomatic pericardial effusions to cardiac tamponade. Our patient with ulcerative colitis presented with acute pericarditis that provided an opportunity to review the literature on cardiac involvement in inflammatory bowel disease. PMID- 7988230 TI - Combined pressure control/high frequency ventilation in adult respiratory distress syndrome and sickle cell anemia. AB - Acute chest syndrome complicating sickle cell anemia may progress to adult respiratory distress syndrome despite appropriate therapy. Extra-alveolar air leaks may complicate the care of these patients as conventional mechanical ventilation becomes increasingly difficult. We successfully treated a child with sickle cell anemia, acute chest syndrome, adult respiratory distress syndrome, and severe extra-alveolar air leaks using a new combined mode ventilatory approach: pressure control with high-frequency ventilation. PMID- 7988231 TI - Bronchial erosion by an indwelling central venous catheter. AB - Despite improved technology, central venous catheters are associated with many complications that occur usually within 48 h of placement. We report a 42-year old man with a rare erosion of a venous catheter (Silastic) into a bronchus 2 years after its insertion. PMID- 7988232 TI - Mycobacterium scrofulaceum infection presenting as lung nodules in a heart transplant recipient. AB - Pulmonary nodules have been reported in up to 10 percent of heart transplant recipients. Most are infectious, with opportunistic pathogens most common. Atypical mycobacteria have not been reported as the etiology of pulmonary nodules in a heart transplant recipient. We report a case of Mycobacterium scrofulaceum infection presenting as three discrete pulmonary nodules. PMID- 7988233 TI - Delayed presentation of anomalous circumflex coronary artery arising from pulmonary artery following repair of aortopulmonary window in infancy. AB - Anomalous origin of the circumflex coronary artery is extremely rare and may cause serious perioperative myocardial injury associated with correction of coexisting congenital malformations. We describe a 15-year-old female patient who underwent surgical correction of an aortopulmonary window at 13 months. Fourteen years later, she presented with dyspnea on exertion associated with angina. On cardiac catheterization, she was noted to have a step-up in oxygen saturation in the pulmonary artery and retrograde filling of the circumflex coronary artery from the left anterior descending coronary artery, with drainage into the pulmonary artery. The patient underwent surgical bypass of the anomalous circumflex coronary artery and ligation of its anomalous origin in the pulmonary artery. Her postoperative course was uneventful, with complete relief of symptoms. We have reviewed this rare congenital anomaly and its therapeutic options. PMID- 7988234 TI - Angioedema following the intravenous administration of metoprolol. AB - A 72-year-old woman was admitted to the hospital with "flash" pulmonary edema, preceded by chest pain, requiring intubation. Her medical history included coronary artery disease with previous myocardial infarctions, hypertension, and diabetes mellitus. A history of angioedema secondary to lisinopril therapy was elicited. Current medications did not include angiotensin-converting enzyme inhibitors or beta-blockers. She had no previous beta-blocking drug exposure. During the first day of hospitalization (while intubated), intravenous metoprolol was given, resulting in severe angioedema. The angioedema resolved after therapy with intravenous steroids and diphenhydramine hydrochloride. PMID- 7988235 TI - Retrosternal goiter associated with chylothorax. AB - We describe a case of chylothorax in a female patient with a large retrosternal goiter. After subtotal thyroidectomy by means of a Kocher cervicotomy, the chylothorax disappeared in 48 h. At present, 2 years after surgical removal, the patient remains asymptomatic, without recurrent pleural chylous effusion. Until now, to our knowledge, only one such case had been reported. PMID- 7988236 TI - Basilic transvenous biopsy for investigation of superior vena caval syndrome. AB - Percutaneous transvenous biopsy of an isolated obstructing mass of superior vena cava (SVC) is reported. Basilic vein access and King's endomyocardial bioptome have been successfully used. Metastatic cancer of SVC has been diagnosed and radiochemotherapy instituted, avoiding an undesirable thoracotomy. PMID- 7988237 TI - Thoracoscopic ultrasonography of the aortopulmonary window. PMID- 7988238 TI - Gastric intramural PCO2 in peritonitis and shock. PMID- 7988239 TI - Sputum specimen quality. PMID- 7988240 TI - Lung cancer surgery. Postoperative complications. PMID- 7988241 TI - Gender and underlying diseases affect the frequency of the concurrence of adult polymyositis/dermatomyositis and interstitial pneumonia. PMID- 7988242 TI - Pressure support level before extubation. PMID- 7988243 TI - The Lung Cancer Study Group: Final analysis. PMID- 7988244 TI - Historic background of the Lung Cancer Study Group. PMID- 7988245 TI - What were the issues of surgical importance in lung cancer treatment in 1977? How did they change over time? AB - The LCSG tested innovative and standard adjuvant treatments aimed at strengthening the effectiveness of surgical resection. The group addressed issues related to standardizing and improving surgical treatment, and the perioperative use of chemotherapy, radiotherapy, and immunotherapy alone and in combination. The surgical leadership, meticulous methodology, and interdisciplinary cooperation mobilized to address these issues made the group the reference standard for thoracic oncology trials. PMID- 7988246 TI - A placebo-controlled randomized double-blind study of adjuvant intrapleural BCG in patients with resected T1N0, T1N1, or T2N0 squamous cell carcinoma, adenocarcinoma, or large cell carcinoma of the lung. LCSG Protocol 771. AB - This article reviews the design and findings of LCSG Protocol 771, a randomized double-blind comparison of postoperative adjuvant intrapleural bacillus Calmette Guerin (BCG) against saline solution placebo control in 473 patients with resected T1N0, T1N1, or T2N0 non-small cell lung cancer. Patients were randomized from August 30, 1977, through October 20, 1980, and follow-up ended on January 1, 1990. There was no evidence of improved survival or time to recurrence among patients given BCG in contrast to earlier promising findings. A calculation suggests that false-positive results due to chance are not uncommon in small preliminary studies, indicating the need for larger confirmatory trials such as LCSG Protocol 771. Other contributions from this Protocol are also reviewed, including data on BCG toxicity, immunologic effects, patterns of recurrence, and identification of prognostic risk groups. PMID- 7988248 TI - Effects of postoperative mediastinal radiation on completely resected stage II and stage III epidermoid cancer of the lung. LCSG 773. AB - Among patients with lung cancer approximately 44% have disease limited to the chest. Patients with early lesions treated surgically have better survival rates than those with more advanced primary disease or nodal involvement. Postoperative irradiation should reduce local or regional recurrence and hopefully reduce systemic relapse. PMID- 7988247 TI - Surgical adjuvant therapy for stage II and stage III adenocarcinoma and large cell undifferentiated carcinoma. AB - The Lung Cancer Study Group (LCSG) randomized 141 patients with resected stage II and III adenocarcinoma and large cell undifferentiated carcinoma to receive postoperative combined chemotherapy with cyclophosphamide, doxorubicin, and cisplatin (CAP) chemotherapy or bacillus Calmette-Guerin (BCG) and levamisole immunotherapy. Careful intraoperative staging was performed on all patients. Before randomization, patients were stratified by stage, weight loss, cardiac arrhythmia, and institution. Prognostic variables such as stage, age, weight loss, and nodal involvement were equally distributed between the two groups. Disease-free survival was significantly prolonged in the group receiving chemotherapy. There was no evidence of a deleterious effect of the immunotherapy. This study indicates that postoperative CAP chemotherapy is effective in prolonging disease-free survival in these patients. PMID- 7988249 TI - The comparison of CAP chemotherapy and radiotherapy to radiotherapy alone for resected lung cancer with positive margin or involved highest sampled paratracheal node (stage IIIA). LCSG 791. AB - This study was conducted to determine the effect of adjuvant chemotherapy on locally advanced resected non-small cell lung cancer. Anatomic eligibility requirements were either positive resection margins or tumor involvement of the highest sampled mediastinal lymph node. One hundred seventy-two patients were randomized to receive either postoperative thoracic irradiation alone or together with six cycles of CAP chemotherapy (cyclophosphamide, doxorubicin, and cisplatin). The chemotherapy arm showed significantly longer recurrence-free survival (p = 0.004). This benefit accrued to patients with both nonsquamous (p = 0.01) and squamous (p = 0.08) cell carcinoma. At 1 year following randomization, there was a 14% difference in survival favoring the chemotherapy arm. Chemotherapy significantly reduced distant metastases. Median survival was 20 months for the chemotherapy arm and 13 months for the radiotherapy alone arm. The 2-year survival rate for the entire study population was 35%. Toxic reactions were primarily predictable hematologic, GI, and alopecia toxicity expected from CAP. Esophagitis was not a significant problem. PMID- 7988250 TI - Adjuvant chemotherapy with cyclophosphamide, doxorubicin, and cisplatin in patients with completely resected stage I non-small cell lung cancer. An LCSG Trial. AB - OBJECTIVE: Two recent studies in resectable non-small cell lung cancer by the Lung Cancer Study Group (LCSG) suggested an advantage to adjuvant therapy with cyclophosphamide, doxorubicin (Adriamycin), and cisplatin (CAP). Neither study had a no-treatment control arm. The purpose of this study was to compare the CAP regimen with no treatment in patients with resectable early-stage non-small cell lung cancer. METHODS: After complete resection, eligible patients with T1N1 or T2N0 non-small cell lung cancer were randomly assigned to receive or not to receive four courses of CAP at 3-week intervals beginning on day 30 after surgery after stratification for histology, preoperative white blood cell count, and Karnofsky performance status before surgery. The CAP regimen consisted of 400 mg/m2 of cyclophosphamide, 40 mg/m2 of doxorubicin, and 60 mg/m2 of cisplatin. Of the 269 eligible patients entered in the study, 101 had recurrence and 127 had died at the time of analysis. The mean time since randomization is 6.4 years; mean follow-up is 3.8 years. There were no differences in time to recurrence or overall survival between the two groups even when analyses were adjusted for prognostic variables. Only 53% of the eligible patients received all four courses of CAP, and only 57% of such patients received all four cycles on time. Among the patients who had recurrences, 74% had their initial recurrence at a distant site. CONCLUSION: No survival benefit for CAP vs no-treatment control was found in this study. Therefore, adjuvant therapy with CAP should not be recommended for patients with resected early-stage non-small cell lung cancer. Further trials to test adjuvant therapy are indicated, but investigators should use better antiemetics to improve patient compliance as well as more active cisplatin-based chemotherapy regimens. PMID- 7988251 TI - A phase 3 randomized trial of immediate combination chemotherapy vs delayed combination chemotherapy in patients with completely resected stage II and III non-small cell carcinoma of the lung. AB - The purpose of this trial (Lung Cancer Study Group [LCSG] 853) was to perform a comparative study of immediate combination chemotherapy (cyclophosphamide, doxorubicin, cisplatin [CAP]) vs delayed combination chemotherapy (CAP) administered at the time of first systemic relapse in patients with completely resected stage II and stage III non-small cell cancer of the lung. We randomly assigned 188 patients with resected stage II or stage III non-small cell lung cancer of the lung (squamous, 53%; nonsquamous, 47%) to receive either immediate or delayed combination chemotherapy. Careful intraoperative staging was performed in all patients. Before randomization, patients were stratified according to stage--II (hilar nodes positive) vs III (mediastinal nodes positive or T3)--and histologic features (squamous vs nonsquamous). Ninety-four patients were randomized to receive immediate CAP vs 94 patients randomized to receive delayed CAP. Prognostic variables such as extent of disease, histologic features, sex, race, TN status, and Karnofsky performance status were equally distributed between randomized groups. The treatment groups differed with respect to greater than 10% weight loss. Forty-one percent of patients had stage II disease and 59% of patients had stage III disease. Median time to recurrence (19.5 months) and survival (32.7 months) did not differ between treatment groups. Immediate combination chemotherapy was associated with a 12% reduction in risk of recurrence and an 18% reduction in risk of death, although these rates were not statistically significant. Histologic features, sex, race, Karnofsky performance status, nodal status, and weight change were associated with higher risks of recurrence. PMID- 7988252 TI - Adjuvant chemotherapy for non-small cell lung cancer. AB - In the late 1970s and early 1980s, the Lung Cancer Study Group conducted a series of adjuvant chemotherapy trials in patients with resected non-small cell lung cancer. Although some of these trials yielded modest survival benefit, the length of improved survival essentially equaled the time spent receiving chemotherapy. Consequently, few physicians routinely employ postoperative chemotherapy in spite of its theoretical appeal. Possible explanations for the failure of adjuvant chemotherapy to provide meaningful prolongation of survival in non-small cell lung cancer include lack of effective chemotherapy, incorrect chemotherapy regimen, inadequate dose intensity, and possibly inadequate trial design. Future postoperative adjuvant trials should focus on treating patients with resected early stage lesions (T1N1, T2N1, T2N0). What role, if any, newer antineoplastic agents will play in the postoperative setting remains to be determined. Neoadjuvant induction chemotherapy may well prove to be a superior treatment strategy and deserves further investigation. PMID- 7988253 TI - The comparison of limited resection to lobectomy for T1N0 non-small cell lung cancer. LCSG 821. AB - The Lung Cancer Study Group, in order to investigate lesser resection within the community as definitive management for T1N0 lung cancers, in 1982 began a prospective trial of limited resection compared to lobectomy for these patients. First reported results demonstrated no significant differences for stratification and other prognostic variables, and no differences in postoperative complication rates. Interim analysis 3 years later suggested a higher local recurrence rate in the limited resection arm of the study. Further comprehensive analysis will be forthcoming. PMID- 7988254 TI - A prospective randomized trial to determine the benefit of surgical resection of residual disease following response of small cell lung cancer to combination chemotherapy. AB - Three hundred twenty-eight patients with limited stage small cell lung cancer were enrolled in a trial to evaluate surgical treatment for such patients responding to chemotherapy. Cyclophosphamide, doxorubicin, and vincristine were administered every 21 days for five cycles. Patients achieving at least partial response who had confirmation of pure small cell histologic features by pathology review and who were fit enough for thoracotomy were randomized to undergo or not to undergo pulmonary resection. All randomized patients received radiotherapy to the chest and brain. Two hundred seventeen (66%) of the patients achieved objective response (90 complete response; 127 partial response). One hundred forty-six patients were randomized (66% of responders, 44% of all patients): 70 to surgery and 76 to no surgery. Results of surgery were 83% resection rate, 19% pathologic complete remission rate, and 9% with residual non-small cell histologic features only, for a total of 28% eradication of small cell lung cancer. The survival curves for the two arms are not different (log rank p = 0.78). Median survivals were 12 months for all enrolled patients and 16 months for those who were randomized. Actuarial 2-year survival is 20%. The results of this trial do not support the addition of pulmonary resection to the multimodality treatment of small cell lung cancer. PMID- 7988255 TI - Quality of life in lung cancer surgical adjuvant trials. AB - The Functional Living Index-Cancer (FLIC) was administered to 438 patients in the Lung Cancer Study Group on whom long-term follow-up was available in 1993. Across all trials, the total FLIC score was predictive for survival even when corrected for extent of disease, although individual items on the FLIC were not. There was no significant impact of a short course of chemotherapy on quality of life. The FLIC is a reliable means of assessing quality of life in lung cancer surgical adjuvant trials. PMID- 7988257 TI - Role of mediastinal staging of lung cancer. AB - The Lung Cancer Study Group (LCSG) assured objective surgical/pathologic staging of clinical trial patients by requiring histologic examination of lymph nodes from anatomically identified specific mediastinal locations. Therefore, within the larger population of heterogeneous patients with lung cancer, subsets of more homogeneous patients were identified. The addition of mediastinal exploration and removal of lymph nodes to the intraoperative procedure did not increase patient morbidity or mortality. The clinical trials designed using surgical/pathologic mediastinal lymph node staging provided definitive answers to several important questions relative to adjuvant and neoadjuvant treatment of patients with non small cell lung cancer. The LCSG recommended that objective histopathologic mediastinal lymph node staging be accepted as the standard of care for patients with lung cancer. PMID- 7988256 TI - Prospective assessment of 30-day operative morbidity for surgical resections in lung cancer. AB - Prospective morbidity and mortality rates associated with resection of lung cancer that are reflective of the current trend toward preoperative therapy are not readily available in the current literature. To determine their prevalence, we prospectively analyzed the results of 783 resections performed within contributing Lung Cancer Study Group (LCSG) centers. There were 543 men and 240 women with a mean age of 63.44 years. Of the 783 resections, there were 411 lobectomies, 135 pneumonectomies, and 237 other procedures. Thirty patients died postoperatively (mortality, 3.8%) and 211 had a major complication (27%). Complications occurred more commonly in men (34.3%, p = 0.001), in patients age 60 or older (34.0%, p = 0.001), and in patients with a Karnofsky index < 9 (44%, p < 0.001). There was no significant difference between mortality, significant morbidity rates for lobectomy (28.2%), and pneumonectomy (31.9%), or for simple (28.3%) and extended resection (31.9%). The seemingly higher incidence of major postoperative events reported in this series not only reflects the prospective nature of this analysis but also the fact that over 25% of patients were in other therapeutic trials involving neoadjuvant or postoperative adjuvant regimens. Within that context, these data appear to be a reasonable estimate of modern surgical morbidity rates in the treatment of lung cancer. PMID- 7988258 TI - General principles of surgery quality control. AB - Randomized clinical trials are currently the most reliable research technique to generate reliable treatment data. Quality control and monitoring with statistical credibility are essential. This requires nurse data managers and coordinators and statisticians, as well as the surgeons and physicians. A well-structured operating infrastructure is key. From the surgical point of view, careful intraoperative staging and standardization of the surgical procedures are a must. Strict eligibility criteria must be documented and enforced. Finally, careful stratification for prognostic variables before randomization in phase 3 trials is essential. PMID- 7988259 TI - Current status of surgical resection for lung cancer. AB - There have been no major breakthroughs in surgical management for primary lung cancer during the past 40 years. Improved 5-year survival relates primarily to improved preoperative staging and appropriate selection of patients for resection. Perioperative morbidity and mortality, however, has been significantly reduced. Certain principles pertain to current surgical management: resection remains the best treatment for patients with localized, non-small cell primary lung cancer. Accurate preoperative diagnosis and staging: whenever possible, it is desirable to establish the diagnosis and cell type before operation. Accurate evaluation of the N status warrants wide application of invasive staging with mediastinoscopy or a variant. Indications for resection: only patients in whom a complete resection is anticipated should be selected for surgery. Such cases included T1 to T4 stages, N0 and N1 tumors, and selected N2 cases. The indication for resection in patients with hematogenous metastases are anecdotal. Intraoperative staging: accurate and deliberate intraoperative staging with evaluation of nodes using the American Thoracic Society map is highly desirable. The nature of nodal metastases exerts a critical influence on prognosis and in the selection of patients for surgical resection. At present, there is no clear indication for adjuvant therapy in surgically resected cases other than for evaluation and clinical trials. PMID- 7988261 TI - Preoperative chemotherapy (cisplatin and fluorouracil) and radiation therapy in stage III non-small cell lung cancer. A phase 2 study of the LCSG. AB - STUDY OBJECTIVE: To determine the feasibility, toxicity, and potential efficacy of neoadjuvant chemoradiotherapy before surgery in patients with non-small cell lung cancer limited to the chest. DESIGN: Phase 2 pilot study. SETTING: Multi institutional, multimodality cooperative group. PATIENTS: Eight-five patients with advanced stage III-A or minimal stage III-B non-small cell lung cancer in whom attempted resection would have been likely to leave residual disease. INTERVENTION: Cisplatin, 75 mg/m2, was given on days 1 and 29; fluorouracil, 1 g/m2 for 24 h, was given as a continuous infusion on days 1 to 4 and 29 to 32; thoracic radiation, 30 Gy in 15 fractions, was administered on days 1 to 19. Thoracotomy with tumor resection was planned for day 57. MEASUREMENTS AND RESULTS: Two patients achieved a complete and 46 achieved a partial response after the neoadjuvant chemoradiotherapy for an overall response rate of 56%. Toxicity was moderate but acceptable. Fifty-four patients underwent thoracotomy and tumor resection was attempted in 44; 29 (34%) had complete and 15 (18%) had incomplete resections. There was no apparent increase in postoperative complications. In eight patients (9%), no viable tumor was detected pathologically in the resection specimen. Of the 18 patients whose tumors were completely resected and had disease recurrence, none had recurrence only in the chest, 15 (83%) had recurrence in distal sites, and 3 (17%) developed second primary tumors. Median survival of all patients was 13 months. CONCLUSIONS: This neoadjuvant regimen did not appear to provide major benefit in patients with advanced but potentially resectable non-small cell lung cancer. Further studies are needed to better define the relative roles of preoperative radiotherapy and chemotherapy. PMID- 7988260 TI - Management of regionally advanced (stage III) non-small cell lung cancer. LCSG 831. AB - Patients with regionally extensive non-small cell lung cancer (predominantly by virtue of metastases to mediastinal lymph nodes, less commonly by direct extension into the mediastinum) were treated predominantly with chest radiation therapy alone until the early 1980s. At that time, because of the high local recurrence rate, the higher likelihood of distant metastases, and the poor 5-year survival rates, studies were begun in these patients attempting to substitute a different local treatment modality (surgery) or to use both radiation therapy and surgery to decrease local recurrence rates and to add chemotherapy as a systemic therapy to decrease distant metastases. LCSG 831 explored the use of CAP (cyclophosphamide, doxorubicin, cisplatin) chemotherapy plus radiation therapy as preoperative or neoadjuvant therapy. Thirty-nine patients entered this phase 2 trial with 33 undergoing resection. Median survival was 11 months, and 1-year survival was 43%. These results are compared with the results of other similar trials. Explanations for the poor and differing results are suggested as are possible ways to improve study design and results. PMID- 7988262 TI - Randomized phase 2 evaluation of preoperative radiation therapy and preoperative chemotherapy with mitomycin, vinblastine, and cisplatin in patients with technically unresectable stage IIIA and IIIB non-small cell cancer of the lung. LCSG 881. AB - Between June 1988 and January 1980, 67 patients with pathologic stage III non small cell lung cancer were randomized to receive either preoperative mitomycin, vinblastine, and cisplatin (MVP) chemotherapy (cisplatin 120 mg/m2, and mitomycin, 8 mg/m2 day 1 + 29, and vinblastine, 4.5 mg/m2 on day 1, 15, 22, and 29 and 2.0 mg/m2 day 8), or preoperative radiotherapy (44 Gy in 22 fractions to the primary tumor and mediastinum). The purpose of this study was to identify a treatment approach that showed sufficient effectiveness and acceptable toxicity to warrant testing by prospective randomized trial against "standard" nonsurgical treatment. All patients had surgical staging of the mediastinum and had either unresectable N2 disease or T4 disease with proximal extension of disease along the pulmonary artery. Response to preoperative therapy was evaluated 8 weeks after beginning treatment and patients with complete or partial radiographic response were to undergo surgical exploration and resection if possible. Fifty seven patients were eligible and evaluable for response. Of the 67 total patients, 3 were unavailable for follow-up, 4 were ineligible, 1 was canceled, and 2 refused all treatment after having been randomized. Of the eligible and evaluable patients, 49 had stage IIIA and 8 had stage IIIB disease. Randomization was to MVP in 26 cases and to radiotherapy (XRT) in 31. Radiographic response to treatment was virtually identical for the two approaches, with 29 of the 57 evaluable patients achieving objective responses. In patients achieving radiographic response, 24 underwent surgical exploration and 20 underwent resection, of which 18 were complete. The mediastinum was free of tumor in seven patients but only two pathologic complete responses were seen (one each to XRT and MVP). In addition, ten nonresponders underwent surgery; seven underwent resection. Median survival for the entire group is 12 months, with a 27% actuarial survival at 4 years. Two patients died of treatment toxicity during preoperative therapy. Overall toxicity included 2 preoperative toxic deaths and 6 postoperative deaths in 34 patients who underwent surgical exploration (3 each with XRT and MVP) due to adult respiratory distress syndrome (3), myocardial infarction (1), pulmonary edema (1), and esophageal fistula (1), for an overall death rate 8 of 57 (14%) and a perioperative death rate in surgically explored patients of 6/34 (18%). These preoperative regimens, in the population studied herein, were of modest efficacy and substantial toxicity.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 7988263 TI - Current status of neoadjuvant therapy for non-small cell lung cancer. AB - Any program of therapy for clinically advanced non-small cell lung cancer (NSCLC) that would increase the incidence of local tumor control and decrease the likelihood of distant metastatic disease would be of obvious benefit. The objective of neoadjuvant therapy is to eradicate the primary tumor and micrometastatic disease. In the past 10 years, many trials have been completed to evaluate neoadjuvant therapy and they have included sequential chemoradiotherapy, concurrent chemoradiotherapy, chemotherapy/surgery, and chemoradiation/surgery. These trials have predominately been phase 2 trials and have demonstrated that chemotherapy is generally well tolerated, surgery is technically feasible, and operative morbidity and mortality are not excessive. Long-term survival for patients with clinically advanced NSCLC is improved when compared with historic controls. These trials have demonstrated a greater than 50% clinical response rate and in approximately 20% of patients who have undergone resections, the tumor is sterilized. This latter group of patients demonstrate significantly improved survival. Cost-benefit ratios and quality of life have yet to be evaluated. Final determination of the effectiveness of neoadjuvant therapy for NSCLC awaits completion of phase 3 trials. PMID- 7988264 TI - Trials in malignant mesothelioma. LCSG 851 and 882. AB - In 1985 the Lung Cancer Study Group (LCSG) initiated clinical trials in malignant pleural mesothelioma because LCSG member institutions had access to large numbers of patients and had significant experience treating this uncommon cancer. The first trial, LCSG 851, defined the patient population seen by the LCSG, and the feasibility of performing surgical resection by extrapleural pneumonectomy in a multi-institutional setting. Of 83 patients entered on this study from September 1985 to June 1988, only 20 could undergo an extrapleural pneumonectomy, and 3 of 20 patients died postoperatively. This experience prompted the LCSG to explore combining a potentially less morbid operation, pleurectomy/decortication, with adjuvant therapy. The results of another LCSG trial (LCSG 861) and of a small single institutional pilot study demonstrated the feasibility of intrapleural cisplatin-based chemotherapy, and led to the development of LCSG 882, which combined pleurectomy/decortication with postoperative intrapleural, and subsequent systemic, cisplatin-based chemotherapy. This study was not completed because of discontinuation of funding for the LCSG. However, a single-institution phase 2 trial of very similar design has subsequently shown the feasibility of this combined modality approach. PMID- 7988265 TI - Intrapleural chemotherapy without pleurodesis for malignant pleural effusions. LCSG Trial 861. AB - Malignant pleural effusions are a common and significant problem in patients with advanced malignancies. In contrast to traditional sclerosing agents, intrapleural chemotherapy has the potential advantage of treating the underlying malignancy, in addition to treating the effusion. The Lung Cancer Study Group evaluated intrapleural cisplatin and cytarabine in patients with malignant pleural effusions from a variety of solid tumors. Forty-six patients with cytologically proven symptomatic and previously untreated malignant pleural effusions were entered. Cisplatin, as a single dose of 100 mg/m2, plus cytarabine 1,200 mg, were instilled into the pleural space via a chest tube that was then immediately removed. The overall response rate, complete plus partial at 3 weeks, was 49% (18/37 patients). One patient experienced reversible grade 3 renal toxic reactions, four patients had grade 3 hematologic toxic reactions, and five patients had grade 3 cardiopulmonary toxic reactions. Median length of response was 9 months for a complete remission and 5.1 months for a partial remission. Although chemotherapy has the potential advantage of treating the underlying malignancy in addition to controlling the malignant effusion, intracavitary cisplatin and cytarabine therapy as administered in this trial appears inferior to existing sclerosing agents for the control of malignant pleural effusions. Although administration is safe, it cannot be recommended for the standard control of malignant pleural effusions, but it may have a role incorporated into combination modality therapies for diseases such as malignant pleural mesothelioma. PMID- 7988266 TI - Impact of neuroendocrine differentiation in non-small cell lung cancer. The LCSG experience. AB - Non-small cell lung cancers with neuroendocrine differentiation (NSCLC-NE) may demonstrate biologic behavior intermediate between non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC) with impact on prognosis. We studied the expression of four well-defined neuroendocrine (NE) markers: neuron-specific enolase (NSE), chromogranin A, Leu-7, gastrin-releasing peptide, and a panel of three non-NE markers, including vimentin, and the epithelial markers carcino embryonic antigen (CEA) by immunohistochemistry, and mucin by histochemistry in 237 resected NSCLCs from patients on six LCSG protocols. Twenty-nine (12%) tumors were positive for 2 or more NE markers. An NE differentiation score was calculated but failed to correlate with recurrence as did other combinations of markers. However, the presence of tissue staining for CEA was strongly associated with improved survival (p = 0.011), whereas the presence of mucin was associated with a worse outcome (p < 0.001). Individually, CEA and mucin remained prognostic even when corrected for stage, histologic features, and performance status. We conclude that NE differentiation is not predictive of recurrence in patients with resected NSCLC but data on patterns of CEA and mucin expression may improve prognostication and permit rational design of new therapeutic approaches. PMID- 7988267 TI - Tumor suppressor and immediate early transcription factor genes in non-small cell lung cancer. AB - Non-small lung cancer (NSCLC) is a disease that exhibits multiple genetic lesions. Lung Cancer Study Group (LCSG) 871 was designed to analyze this group of malignancies for alterations in growth factors and/or their receptors, oncogenes, tumor suppressor genes, and immediate early transcription factor genes. Immunohistochemical analysis showed that 32% of evaluable cases studied contained absent or abnormal Rb expression. Sequence analysis of the p53 gene revealed that 58% of these cancers contained structural alterations of this gene, whereas only 45% of these cases overexpressed p53 by immunohistochemical analysis. Finally, both Northern blot and immunohistochemical analysis showed that these tumors exhibited changes in the mRNA and protein expression levels respectively of the immediate early transcription factor genes c-fos, c-jun, and EGR, in that less expression of these genes was evident in the tumors compared with adjacent normal tissue. Understanding both the biologic and molecular significance of these findings may allow us to explore novel modalities for treatment of this disease. PMID- 7988268 TI - p53 immunostaining positivity is associated with reduced survival and is imperfectly correlated with gene mutations in resected non-small cell lung cancer. A preliminary report of LCSG 871. AB - We investigated the correlation of p53 abnormalities with survival in 85 patients with non-small cell lung cancer (NSCLC) who had undergone resection with curative intent as part of Lung Cancer Study Group (LCSG) 871. Our previous studies showed that only a subset of p53 mutations in lung cancers result in overexpression. In addition, protein overexpression has been described in the absence of mutation. Therefore, we determined both p53 protein overexpression (by immunostaining) and p53 and ras gene mutations (by single-strand conformation polymorphism and DNA sequencing) in this set of resected tumor specimens. Clinical follow-up data were available for 75 cases. Of the studied patients, 64% showed p53 overexpression and 51% had mutant p53 sequences; however, the concordance rate was only 67%. There was a negative survival correlation with positive p53 immunostaining (p = 0.05), but not with the presence of gene mutations (p = 0.62) in this group of patients. Overexpression of p53 protein determined by immunostaining may contribute to adverse outcome due to the ability of p53 to act as a dominant oncogene, or alternatively, overexpression may reflect ongoing DNA damage in the tumor as a marker for a more aggressive behavior. When adjusted for stage, age, and gender by multivariate analysis, however, there was no independent impact of p53 overexpression on survival. PMID- 7988269 TI - The adverse effect of perioperative blood transfusion in lung cancer. AB - Perioperative blood transfusion appears to increase the risk of recurrence and death in patients with surgically resected lung cancer. This finding is consistent with that in other cancers and several studies in lung cancer report similar risk elevations. We have reanalyzed the Lung Cancer Study Group data relevant to this question, assessing the potential confounding effects of some prognostic factors not examined previously. The results are nearly identical to those reported earlier, suggesting that increased risk is attributable to blood transfusion and not to confounding by known prognostic factors. PMID- 7988270 TI - The early detection of second primary lung cancers by sputum immunostaining. LCEWDG Investigators. Lung Cancer Early Detection Group. AB - STUDY OBJECTIVE: To determine whether monoclonal antibody (Mab) detection of tumor-associated antigen expressed on sputum epithelial cells precedes clinical presentation of second primary lung cancer. DESIGN SETTING/PARTICIPANTS: Eleven oncology centers collaborate in the accrual of 1,000 patients with stage I non small cell lung cancer (NSCLC) who had undergone resection. The Mabs examined in this study (624H12, 703D4) detect two promising oncofetal/differentiation markers (ie, a difucosylated Lewis X and a 31-Kd glycoprotein antigen). INTERVENTIONS: Induced sputum specimens are evaluated for quality, then are Papanicolaou and immunostained by independent central laboratories at enrollment and annually thereafter. The predictive value of Mab markers is compared with routine morphologic study for detection of second primary lung cancer during an anticipated 3 years of accrual and 1 year of follow-up. MEASUREMENTS AND RESULTS: Five hundred eighty of an anticipated 1,000 patients have been accrued on schedule. Patients are primarily white (88.6%), former smokers (75.9%), men (55.6%), with a median age of 66.7, and joined the study at an average of 3.7 years following resection of a stage 1 NSCLC (34.4% squamous, 43.6% adenocarcinoma). Central laboratories found less dysplasia and more unsatisfactory specimens (27.3%) than do the accrual institution laboratories. Immunostaining identifies more suspicious cells than does morphologic study. However, only two second primary lung cancers (eight total deaths) have occurred to date. CONCLUSIONS: Halfway through the accrual, we describe the study design and preliminary observations. This study illustrates rational selection of carcinogenesis markers by linkage of marker expression on preneoplastic specimens with subsequent expression on tumor tissue. PMID- 7988271 TI - The role of CT and MRI in staging of the mediastinum. AB - Lung Cancer Study Group (LCSG) Protocol 883, the comparative study of the results of magnetic resonance imaging (MRI) and computerized tomography (CT) for staging of tumor, nodal, and selected metastatic sights in patients with surgically staged lung cancer was activated in August 1988 but was not completed because of termination of LCSG funding. A literature review was therefore undertaken to determine the results of other studies that were performed to evaluate the relative efficacy of MRI and CT in the staging of patients with lung cancer. These studies determined that CT and MRI are approximately equal in the staging of N2 disease with a sensitivity of 70 to 90%, a specificity of 60 to 90%, and an accuracy of 66 to 90% depending on the criteria used for determining positive nodes and the compulsiveness of surgical staging. Magnetic resonance imaging is probably better in the assessment of superior sulcus tumors, tumors involving the aorta-pulmonary window, hilar nodes, in assessing chest wall or diaphragmatic invasion, and in evaluating patients whose CT findings are equivocal. Computed tomography and MRI reveal adrenal abnormalities in 10 to 20% of patients but only one third of these have metastases. Mediastinoscopy has a sensitivity of 85 to 90%, a specificity of 100%, and an accuracy of about 95% and is therefore the gold standard for N2 staging. If the CT examination reveals no N2 disease, one can proceed directly to thoracotomy with approximately a 15% chance of finding N2 disease. It was concluded that because CT is much cheaper, it should therefore be used for the noninvasive staging of patients with lung cancer unless the above noted special circumstances are present that have been shown to favor MRI. Because of the limited accuracy of CT and MRI, however, positive findings must be confirmed by biopsy specimens and pathologic study. PMID- 7988272 TI - Esophageal cancer. Early efforts and proposals of the LCSG. AB - The Lung Cancer Study Group, just prior to its demise, initiated efforts to develop clinical trials comparing primary resection for esophageal cancer with multimodality therapy. In initiating these proposals, a new staging system and map were developed that conformed to the staging system available for pulmonary malignancies. This staging system and map are currently being used by the ongoing intergroup trial in North America (INT-113). PMID- 7988273 TI - Future directions in clinical research for lung cancer. AB - Even since the Surgeon General's 1964 report, the mortality rate from lung cancer has continued to rise. Although there is evidence that this continued increase in mortality will slow or level in the next decade, lung cancer mortality is a major health problem destined to remain with us for at least the next generation. There have been no established advances in the early detection or prevention of lung cancer in the last 30 years and our therapies have increased the cure rate only from 5 to 13% in this 30-year interval. Biologic advances have outpaced clinical advances in recent times and many of the advances are now ripe for clinical exploitation. There are currently more exciting clinical trials for all phases of lung cancer than at any time and it will be stimulating to witness the results of the clinical trials discussed herein. Hopefully, the results of these studies will lead to a decrease in lung cancer mortality in the next century, much as it increased in the past century. PMID- 7988274 TI - Should we reestablish the Lung Cancer Study Group? AB - The hallmark of the Lung Cancer Study Group (LCSG) was its multidisciplinary approach to cancer management, based on close collaboration among thoracic surgeons, medical oncologists, radiation oncologists, pathologists, biostatisticians, and data managers. Discontinuation of funding for the group dispersed a critical mass of thoracic oncologists and had serious adverse effects on clinical trials in early-stage thoracic malignancies, on translational research, and on oncologic education. The use of an intergroup mechanism for clinical trials has been partially successful in continuing the work started by the LCSG, but a sustained effort will be necessary to recreate the framework for clinical investigation provided by the group. PMID- 7988275 TI - Collaboration of a public child welfare agency and a school of social work: a clinical group supervision project. AB - As an addition to the growing literature on school of social work/child welfare agency collaborations, this article describes a clinical group supervision arrangement between Children and Youth Services of Delaware County, Pennsylvania, and the master of social work program at Widener University's Center for Social Work Education in Chester, Pennsylvania. Six students who were also employees of the department received clinical group supervision every other week by a faculty member of the center. The process of initiating the group, the supervision issues that emerged, the articulation and application of a model of child-centered family treatment, and preliminary results from the use of a Skill-Level Self Rating scale are presented and discussed. PMID- 7988276 TI - The county child abuse protocol system in Georgia: an interagency cooperation approach to a complex issue. AB - In 1987, the Georgia Legislature mandated that each of its 159 counties establish a formal committee made up of representatives from law enforcement, child protective services, school systems, and county child advocacy groups to handle cases of sexual and physical abuse of children, in an effort to eliminate chronic mishandling of serious cases of abuse caused by the lack of a forum for bureaucratic cooperation. No funding was provided to implement the mandate. This article reports research findings that document the protocol committees' activity levels, discusses changes in organizational patterns brought about by the committee system, and offers insight into the degree to which "mandates without money" can influence organizational cooperation. PMID- 7988277 TI - A longitudinal study of special-needs adoptive families. AB - This longitudinal study of special-needs adoptive families assesses change on several measures of adoption outcome. Outcomes were somewhat more negative at the second administration of the survey than at the initial administration, presumably because many of the study children had entered adolescence. On balance, however, the outcomes were still positive at the second administration. Findings support the need for enhanced postadoptive services. PMID- 7988278 TI - A strengths approach to ethnically sensitive practice for child protective service workers. PMID- 7988279 TI - Understanding the parents who are mentally retarded: guidelines for family preservation programs. AB - This article reviews eight programs in New York State that provide parenting training and direct assistance to parents who are mentally retarded. Common lessons learned by the programs are discussed and guidelines are set forth on staffing, family enrollment and retention, service provision, and risk-management practices for work with similar clients. The families in these programs are briefly profiled, based on data collected on approximately half of the parents and children. PMID- 7988280 TI - [Reductive dechlorination of chlorophenols by an anaerobic mixed culture]. AB - In this study, we investigated the potential for reductive dechlorination of chlorophenols by municipal sewage sludge acclimated to 2,4-dichlorophenol (2,4 DCP) and 3,4-dichlorophenol (3,4-DCP). The optimal temperature and pH for dechlorination of 2,4,6-trichlorophenol (2,4,6-TCP) were 30 degrees C and 7.2. Dechlorination of 2,4,6-TCP was inhibited by sulfate, nitrate, or ferric (III), but was increased by manganese (IV) except that product of 2,4-DCP was accumulated. Organic substrates such as pyruvate or acetate did not influence dechlorination of 2,4,6-TCP, but increased dechlorination of 2,4-DCP; nevertheless lactate showed no influence on dechlorination. When glucose was added as substrate, only 20% of 2,4,6-TCP dechlorination was found. Addition of methanogenesis inhibitor 2-bromoethane sulfonate did not influence dechlorination, but addition of eubacteria inhibitor vancomycin showed no dechlorination activity at the first few days, and finally complete transformation and accumulation of 2,4-DCP occurred. Because mixed culture was from Di-Hwa Wastewater Treatment Plant, adding the same water as culture medium was found to increase the dechlorination of 2,4,6-TCP and its product 2,4-DCP. Dechlorination by adding wastewater of Petroleum Corporation was also increased, especially for 2,4-DCP product, but only 7% of 2,4,6-TCP dechlorination was found after incubation with Hou-Chin river water for 14 days. PMID- 7988281 TI - Serodiagnosis of tuberculosis using the A60 IgG ELISA. AB - The serodiagnosis of tuberculosis (TB) by using an enzyme-linked immunosorbent assay (ELISA) to detect IgG against mycobacterial antigen 60 (A60) was evaluated. Forty-three controls (10 healthy adults, 19 patients with non-tuberculous pulmonary diseases and 14 patients with non-pulmonary infectious diseases) and 63 patients with TB in different disease activity (50 patients with active TB and 13 patients with old pulmonary TB) were studied. When a cut-off value of 200 units was selected, the results obtained with controls were: 100% negative in IgG titers in healthy adults and patients with non-pulmonary infectious diseases, 89% negative in IgG titers in patients with non-tuberculous pulmonary diseases. The overall "false positive" rate was 5% in the control groups. The percentage of serologically positive cases of active TB was: 82% in smear-positive, 67% in smear-negative/culture-positive and 38% in culture-negative. Of the 13 patients with calcified pulmonary TB, four had a positive serological response (31%). Four out of eight patients with active TB showed an elevation in IgG titer 1 to 3 months after diagnosis and anti-TB chemotherapy. The positive and negative predictive values of the test may provide valuable information according to the prevalence of TB in different populations. When the TB prevalence is high, a positive IgG ELISA test may support the diagnosis of active TB. PMID- 7988282 TI - A new influenza virus A/H3N2 variant of Taiwan origin. AB - A clinical isolate of influenza virus A/H3N2 from a one-year-old boy with pharyngitis was examined by using RNA-polymerase chain reaction (PCR) for amplification of viral cDNA and subsequent DNA sequencing with asymmetric PCR. Since antigenic drift has been found in recent A/H3N2 isolates, this strain was compared with A/Shanghai/24/90 and other A/H3N2 strains, collected at the Centers for Disease Control and Prevention (CDC) in Atlanta, GA, USA. It was found that the steady changes of amino acid at location 190 and 262 of HA1 region were very similar to some recent isolates. This 1989 isolate may be the origin of a new influenza virus A/H3N2 variant. PMID- 7988283 TI - [Surveillance of scrub typhus in Taiwan]. AB - Although scrub typhus, a rickettsial exanthematous febrile disease, has designated as a reportable communicable disease in Taiwan since 1955, only Pescadores island, Hualien and Taitung counties had more reported and confirmed cases. Suspected dengue fever and scrub typhus serum specimens sent from the Bureau of Health and health stations to this institute from January 1991 to December 1992 were tested for antibody to scrub typhus by indirect fluorescent antibody technique (IFA). The results showed that: 1) there were serologically positive cases in many counties except Hsinchu and Iilan, 2) the disease occurred mostly from July to October, 3) more males than females were infected and their age ranged from 21 to 60 years old with a peak of the twenties and 4) higher incidence rate in children under five years old was observed in Pescadores and Orchid islands. The above data call the attention of people and physicians to be aware of the fact that there were probable scrub typhus cases in every county in Taiwan. PMID- 7988284 TI - Probing chromatin with the scanning force microscope. AB - With the scanning force microscope (SFM), one can image the topography of biological material adsorbed at air-solid or liquid-solid interfaces with up to nanometer resolution. In principle, fixation, contrast enhancement, and labeling are not required. We have adapted specimen preparation techniques of conventional electron microscopy for visualizing chromatin ultrastructures in the SFM. A beaded substructure of the nucleoprotein filament was obtained after hypotonic lysis of chicken erythrocytes and air drying. The beads-on-a-string morphology of the basic nucleosomal assembly was well delineated. The nucleosomes appeared as round protrusions with an apparent height of 4-6 nm. The histogram of center-to center distances between adjacent nucleosome cores along the filament axis had a peak at approximately 30 nm. Reversible changes in the three-dimensional structure were observed upon exposure of air-dried samples of metaphase chromosomes to solutions of different ionic strengths. PMID- 7988286 TI - Molecular cloning of cDNAs encoding variants of meiotin-1. A meiotic protein associated with strings of nucleosomes. AB - Meiotin-1 is a chromatin-associated protein, originally isolated from microsporocytes of Lilium longiflorum, which is found predominantly in cells undergoing meiotic prophase. Chromatin fractionation studies demonstrated that meiotin-1 has an unusual stoichiometry relative to that of histone H1 and the core histones in chromatin fibers. The protein is found less frequently than is histone H1, and appears to be distributed once every 5 to 13 nucleosomes. This distribution may approximate the number of nucleosomes per turn of the chromatin solenoid. A truncated cDNA was identified by immunoscreening of an expression library, and the cDNA was used as a hybridization probe to select a full length cDNA. Variations between the sequence of the predicted polypeptide and sequenced peptides, and variations between the amino acid composition of the protein and the deduced protein indicate that the cDNAs encode minor variants of mature meiotin-1. RNA gel blot hybridization studies reveal that the meiotin-1 mRNA is restricted to anthers in which meiosis is occurring. Computer analysis of the polypeptide deduced from the cDNA indicates that the protein begins with a region highly homologous to the conserved central globular domain of histone H1 molecules. DNA gel blotting experiments demonstrate that homologous sequences exist in the genomes of a fern, a fungus, and both mono- and dicotyledonous plants. Meiotin-1 has been evolutionarily conserved and I propose that it arose from histone H1 to fulfill a role in organizing meiotic chromatin. PMID- 7988287 TI - Alpha satellite DNA in neotropical primates (Platyrrhini). AB - The alpha satellite DNA of Old World (catarrhine) primates usually consists of similar, but not identical, ca. 170 bp sequences repeated tandemly hundreds to thousands of times. The 170 bp monomeric repeats are components of higher-order repeats, many of which are chromosome specific. Alpha satellites are found exclusively in centromeric regions where they appear to play a role in centromere function. We have found that alpha satellite DNA in neotropical (New World; platyrrhine) primates is very similar to its Old World counterpart: it consists of divergent ca. 170 bp subsequences that are arranged in tandem arrays with a ca. 340 bp periodicity. New and Old World alpha satellites share about 64% sequence identity overall, and contain several short sequence motifs that appear to be highly conserved. One exception to the tandemly arrayed 340 bp motif has been found: the major alpha satellite array in Chiropotes satanas (black bearded saki) has a 539 bp repeat unit that consists of a 338 bp dimer together with a duplication of 33 bp of the first monomeric unit and 168 bp of the second monomeric unit. PMID- 7988285 TI - TEL+CEN antagonism on plasmids involves telomere repeat sequences tracts and gene products that interact with chromosomal telomeres. AB - In Saccharomyces cerevisiae, circular plasmids that include either a centromere (CEN-plasmids) or a telomere sequence (TEL-plasmids) segregate more efficiently than circular ARS-plasmids. In contrast, circular plasmids that include both telomere and centromere sequences were unstable, a property we term TEL+CEN antagonism. TEL+CEN antagonism required a telomere repeat tract longer than 49 bp although the distance and relative orientation of the centromere and telomere sequences was not critical. TEL+CEN antagonism was alleviated in strains carrying different rap1 alleles including rap1ts, rap1s, and rap1t alleles. Mutations SIR2, SIR3, SIR4, NAT1 and ARD1, genes that influence transcriptional silencing at telomeres and at the silent mating type loci, abolished TEL+CEN antagonism Mutation of SIR1 also partially alleviated TEL-CEN antagonism. In some sir mutant strains short yeast artificial chromosomes (YACs), which are normally unstable, became more stable, suggesting that the same mechanism that caused TEL+CEN antagonism on circular plasmids may contribute to the instability of short linear plasmids. PMID- 7988288 TI - Cytochemical and immunocytochemical study of coiled bodies in different cultured cell lines. AB - We analyzed by different cytochemical and immunocytochemical approaches the biochemical compositon of coiled bodies in three different cultured cell lines. Coiled bodies are stained by the AgNOR staining method and by the EDTA regressive staining method preferential for ribonucleoprotein (RNP). Using the in situ polyadenylate nucleotidyl transferase-immunogold technique or anti-RNA antibodies, we decisively demonstrated the presence of appreciable amounts of RNA in coiled bodies. Neither the in situ terminal deoxynucleotidyl transferase immunogold technique nor anti-DNA antibodies revealed any DNA in coiled bodies. Coiled bodies thus appear as distinct regions of cell nuclei involved in some steps of RNA metabolism but not directly in RNA synthesis. Their relationships with the dense fibrillar component of the nucleolus and with interchromatin granule clusters are discussed. PMID- 7988290 TI - The nuclear position of pericentromeric DNA of chromosome 11 appears to be random in G0 and non-random in G1 human lymphocytes. AB - The nuclear topography of pericentromeric DNA of chromosome 11 was analyzed in G0 (nonstimulated) and G1 [phytohemagglutinin (PHA) stimulated] human lymphocytes by confocal microscopy. In addition to the nuclear center, the centrosome was used as a second point of reference in the three-dimensional (3D) analysis. Pericentromeric DNA of chromosome 11 and the centrosome were labeled using a combination of fluorescent in situ hybridization (FISH) and immunofluorescence. To preserve the 3D morphology of the cells, these techniques were performed on whole cells in suspension. Three-dimensional images of the cells were analyzed with a recently developed 3D software program (Interactive Measurement of Axes and Positioning in 3 Dimensions). The distribution of the chromosome 11 centromeres appeared to be random during the G0 stage but clearly non-random during the G1 stage, when the nuclear center was used as a reference point. Further statistical analysis of the G1 cells revealed that the centromeres were randomly distributed in a shell underlying the nuclear membrane. A topographical relationship between the centrosome and the centromeres appeared to be absent during the G0 and G1 stages of the cell cycle. PMID- 7988289 TI - Structure, molecular evolution and maintenance of copy number of extended repeated structures in the X-heterochromatin of Drosophila melanogaster. AB - The 60 kb repeats located in the distal heterochromatin of the X chromosome of Drosophila melanogaster were cloned in overlapping cosmids. These regions, designated as SCLRs, comprised the following types of repeated elements: Stellate genes, which are known to be involved in spermatogenesis; copia-like retrotransposons; LINE elements, including amplified Type I rDNA insertions; and rDNA fragments. The following steps in SCLR formation were hypothesized: insertion of mobile elements into the rDNA and Stellate gene clusters; internal tandem duplication events; recombination between the rDNA cluster and Stellate tandem repeat; and amplification of the whole SCLR structure. There are about nine SCLR copies per haploid genome, but there is approximately a twofold variation in copy number between fly stocks. The SCLR copy number differences between closely related stocks are suggested to be the result of unequal sister chromatid exchange (USCE). The restricted variation in SCLR copy number between unrelated stocks and the absence of chromosomes free of SCLRs suggests that natural selection is active in copy number maintenance. PMID- 7988291 TI - Comparison of phase-contrast and fluorescence digital autofocus for scanning microscopy. AB - Reliable autofocus is required to obtain accurate measurements of fluorescent stained cellular components from a system capable of scanning multiple microscope fields. Autofocus could be performed directly with fluorescence images, but due to photobleaching and destructive fluorescence by-products, it is best to minimize fluorescence exposure for photosensitive specimens and live cells. This exposure problem could be completely avoided by using phase-contrast microscopy, implemented through the same optics as fluorescence microscopy. The purpose of this work was to evaluate functions for both phase-contrast and fluorescence autofocus and determine the suitability of phase-contrast autofocus for fluorescence microscopy. Eleven autofocus functions were independently evaluated for fluorescence and phase-contrast microscopy. The most suitable functions were then chosen from these and phase-contrast and fluorescence autofocus were compared on scans each comprising more than 1,000 microscope fields. Autofocus standard deviation (S.D.) of better than 100 nm was achieved for both phase contrast and fluorescence. There was a measurable difference between the best focus positions in the two modes, but the difference was constant enough to be measured and corrected, suggesting the possibility of using phase contrast to predict best focus in fluorescence microscopy. The scanning experiments also showed that autofocus can be performed at least as fast as 0.25 s/field without loss of precision. PMID- 7988292 TI - Counting, measuring, and mapping in FISH-labelled cells: sample size considerations and implications for automation. AB - Statistical models are used to investigate the need for automation in several potential areas of application of FISH-labelling techniques, including perinatal and tumour cytogenetics, genetic toxicology, and gene mapping. Predictions of the models, based on current estimates of likely error rates for spot-counting and measuring, suggest that a fully automated system is a realistic prospect for detecting full or high-level mosaic trisomies and that interactive systems have the potential to reduce substantially the human workload required to detect residual malignant disease or radiation-induced chromosome aberrations. There appear to be no foreseeable limits to the requirements for speed and accuracy in such systems, since there is effectively no lower limit to the level of relevant biological detail that can be investigated with these techniques. PMID- 7988294 TI - Flow cytometric analysis of the cell cycle in polyamine-depleted cells. AB - Polyamines are found in all cells but their function is not fully understood. We have studied the effect of polyamines on the passage of cells through the cell cycle using a polyamine auxotrophic mutant, CHO-P22, which has no detectable ornithine decarboxylase activity. The ability of these cells to grow without serum allows efficient polyamine depletion. A flow cytometric analysis of DNA content and bromodeoxyuridine labeling showed that without added polyamines the cells accumulated in S-phase, the rate of DNA synthesis was retarded, and the entry into mitosis was blocked. Addition of polyamines to cultures deprived of polyamines induced cells in all phases of the cell cycle to reinitiate cycling. Earlier studies have shown that cells with damaged DNA are blocked from entering into mitosis but caffeine can partly overcome this block and induce premature chromosome condensation. Polyamine-depleted CHO-P22 cells responded to caffeine in the same way as cells with damaged DNA. These results show that polyamine depletion in CHO-P22 cells primarily affects DNA synthesis. The finding that polyamine-starved cells continuously take up bromodeoxyuridine without a corresponding increase in the amount of DNA is compatible with extensive repair of erroneous and/or damaged DNA. Polyamine auxotrophic Chinese hamster ovary (CHO) cells might be useful in studies on the regulation of mitosis in mammalian cells. PMID- 7988293 TI - Interactive computer-assisted analysis of chromosome 1 colocalization with nucleoli. AB - The applications of DNA cloning and fluorescent in situ hybridization (FISH) techniques have strengthened the hypothesis of an ordered chromatin structure in interphase nuclei, strongly suspected to vary with functional state. The nonrandom distribution of the centromeres and their dynamic rearrangement during the cell cycle have been well documented. A close proximity of specific centromeres to nucleoli has also been reported, but the functional meaning of this association is still unknown. In order to investigate whether the chromosome 1 centromere region to nucleolus association depends on the cell cycle and chromosome status, we combined FISH of probes specific for the 1q12 region with Ki-67 nucleolar antigen fluorescent immunocytochemical (FICC) detection on the MCF-7 human breast cancer cell line and on the MRC-5 normal fibroblastic cell line. Both FISH and FICC signals were interactively localized in a one-step fluorescent microscopic observation and further analyzed using the Highly Optimized Microscope Environment (HOME) graphics microscope workstation, which provided computerized interactive marking of 1q12 to nucleolus associations (1q12 nu) at the individual nucleus and nucleolus levels. This study confirms that centromeric regions, other than those adjacent to the major ribosomal cistrons, contribute to the perinucleolar chromatin and demonstrate that, during the cell cycle, the heterochromatic band 1q12 is dynamically rearranged with regard to both the nuclear volume and the nucleoli. A relationship between the association of the chromosome 1 pericentromeric region with nucleoli and the nucleolar transcriptional activity is also strongly suggested. PMID- 7988295 TI - Insulin binding to human cultured lymphocytes measured by flow cytometry using three ligands. AB - The binding of insulin to cultured IM-9 human lymphocytes was studied by flow cytometry using FITC-insulin and biotinylated insulins coupled to streptavidin phycoerythrin (N alpha beta 1-biotinylinsulin (B-insulin) and N alpha B1 (biotinyl-epsilon-aminocaproyl)insulin (NBC-insulin)). The reference methods were 125I-insulin binding and the insulin-antiinsulin antibody complexes for flow cytometry. There was a close correlation between 125I-insulin binding and increase in fluorescence for B-insulin, NBC-insulin, and insulin-anti-insulin antibody complexes, but not for FITC-insulin. NBC-insulin gave the largest increase in fluorescence (79 +/- 9 channels) and the the insulin-antiinsulin antibody complexes the smallest (34 +/- 2 channels) (P < 0.05). FITC-insulin and B-insulin gave similar results: 47 +/- 6 and 59 +/- 6 channels. The concentration reducing 125I-insulin binding by 50% was 1.1 x 10(-9) M for native insulin, 2.7 x 10(-9) M for B-insulin, 3.3 x 10(-9) M for NBC-insulin, and 6.6 x 10(-9) M for FITC-insulin (P < 0.05). Nonspecific binding was low for B-insulin and NBC insulin but reached 75% for 10(-6) M FITC-insulin. These results suggest that B insulin and NBC-insulin are suitable ligands for insulin binding studies using flow cytometry. This two-step procedure is easier than the insulin-antiinsulin antibody complex technique. Its poor affinity, specificity, and sensitivity make FITC-insulin less suitable. PMID- 7988296 TI - Pattern sorting: a computer-controlled multidimensional sorting method using k-d trees. AB - Multidimensional binary trees provide a memory efficient and general method for computing sorting decisions in real time for a flow cytometer. Their fundamental advantage over conventional lookup table sorting techniques is that sort criteria in the full N-dimensional data space which cannot be described by projections onto two-dimensional parameter planes can be effectively implemented. This becomes particularly relevant when multidimensional analysis methods such as principal components or clustering are employed. We describe a prototype implementation of this method and point out other possible implementations. PMID- 7988297 TI - In-shoe foot pressure measurements in diabetic patients with at-risk feet and in healthy subjects. AB - OBJECTIVE: To measure in-shoe foot pressures in diabetic patients and healthy subjects and compare them with the foot pressures when they walked without their shoes. RESEARCH DESIGN AND METHODS: Forty-four diabetic patients at risk of foot ulceration and 65 healthy subjects were matched for age, sex, race, and weight. Neuropathy was evaluated clinically, and the F-Scan program was used to measure the foot pressures. Foot pressures were measured with the sensors placed in the shoes (S measurements), between the foot and the sock with shoes (H measurements) or with their socks alone (B measurements). RESULTS: In the control group, significant differences were found between S (4.77 +/- 1.87 kg/cm2) and H measurements (5.12 +/- 1.87 kg/cm2, P < 0.001), between S and B (7.23 +/- 2.95 kg/cm2, P < 0.0001), and between H and B (P < 0.0001). In the diabetic group, no difference was found between S and H measurements (5.28 +/- 2.22 vs. 5.27 +/- 2.39 kg/cm2, NS). In contrast, the B pressure was significantly higher when compared with both (8.77 +/- 4.67 kg/cm2, P < 0.02). When compared with the control group, the S and H pressures did not differ significantly, but the B pressure in the diabetic group was significantly higher (P < 0.02). The peak S pressure was above the normal limit in 24 (27%) diabetic and 21 (16%) control feet (P < 0.05), the H pressure in 17 (19%) diabetic feet and 22 (17%) control feet (NS), and the B pressure in 24 (27%) diabetic and 21 (16%) control feet (P < 0.05). CONCLUSIONS: In-shoe foot pressure measurements are significantly lower than the ones measured when walking with the socks only in both diabetic patients and healthy subjects. The shoes of diabetic patients provided a higher pressure reduction than did those of the control group, but the number of feet with abnormally high pressures did not change. The F-Scan system may be particularly helpful in designing footwear suitable for diabetic patients with at-risk feet. PMID- 7988298 TI - Feasibility of insulin-glucose infusion in diabetic patients with acute myocardial infarction. A report from the multicenter trial: DIGAMI. AB - OBJECTIVE: To investigate the effect of insulin-glucose infusion on metabolic control and hypoglycemic episodes and its feasibility and safety in patients with diabetes and myocardial infarction (MI) compared with conventional treatment. RESEARCH DESIGN AND METHODS: Of 327 patients with suspected acute MI 158 were randomized to insulin-glucose infusion for at least 24 h and 169 received conventional therapy. We determined the 24-h blood glucose profile in the infusion group, the degree of metabolic control, hypoglycemic events, and in hospital complications within the two study groups. RESULTS: Blood glucose fell from 14.6 +/- 2.9 to 9.2 +/- 2.9 mM during the first 24 h in patients receiving insulin-glucose and from 15.8 +/- 4.3 to 12.0 +/- 4.4 mM in control patients (P < 0.01). Serum potassium decreased 0.21 +/- 0.56 mM in the infusion group (P < 0.001) and 0.11 +/- 0.59 mM in the control group (P < 0.05). The difference between the groups was not significant. Twenty-eight of the 158 patients developed an episode of hypoglycemia (blood glucose < 3.0 mM) during the insulin glucose infusion. There were no significant differences in the number of episodes of ventricular tachyarrhythmias or in ischemic events between patients with and without hypoglycemia. CONCLUSIONS: The protocol outlined in this study gives more rapid and better metabolic control than does conventional treatment. This treatment seems to be a feasible alternative for clinical attempts. Before it can be recommended for general use, the impact on mortality needs to be evaluated. PMID- 7988299 TI - Arginine-induced insulin release in glucokinase-deficient subjects. AB - OBJECTIVE: In eight glucokinase (GCK)-deficient subjects, we have investigated insulin secretion rates (ISRs) in response to intravenous arginine. Impairment in the enzymatic activity of mutant GCK leads to a reduced glycolytic flux in beta cells. This defect translates in vivo as a right shift in the glucose/SR dose response curve. Insulin secretion in response to other secretagogues has not been reported. RESEARCH DESIGN AND METHODS: The arginine test was performed immediately after a 2-h hyperglycemic (10 mM) clamp. ISR was computed by deconvolution of peripheral C-peptide levels. Linear regression analyses were performed to assess correlations between the beta-cell secretory responses to the arginine test, an intravenous glucose tolerance test (IVGTT), and a hyperglycemic clamp (areas under the C-peptide curves), and between these parameters and the glucose tolerance status (area under the glucose curve during an oral glucose tolerance test). RESULTS: Two minutes after the injection of arginine, the increment in ISR was 30.17 +/- 10.01 pmol insulin.kg-1.min-1 in patients and 36.25 +/- 15.46 pmol insulin.kg-1.min-1 in control subjects (P = 0.38). Throughout the experiment, increments in ISR were comparable in both groups. The amount of insulin secreted in response to arginine (0-5 min) was similar in patients and control subjects: 81 +/- 28 vs. 119 +/- 55 pmol/kg (P = 0.16), respectively. The arginine test C-peptide response was not correlated with the IVGTT or hyperglycemic clamp responses. The arginine test and hyperglycemic clamp responses were not correlated to the glucose tolerance status. The best predictor of the glucose tolerance was the C-peptide response to the IVGTT (r2 = 0.78; P = 0.002). CONCLUSIONS: beta-cell secretory increment in response to arginine was found to be in the normal range in GCK-deficient subjects. The arginine test does not seem to reflect either the beta-cell secretory defect or the glucose tolerance status of these subjects. IVGTT seems to be the best predictor of the latter parameter in this population. PMID- 7988300 TI - Establishment of a registry and incidence of IDDM in Avellaneda, Argentina. AB - OBJECTIVE: To provide reliable data on the incidence of insulin-dependent diabetes mellitus (IDDM) in children (< 15 years of age) in Avellaneda, Argentina. RESEARCH DESIGN AND METHODS: A registry was established in Avellaneda, Argentina. The first registry was started in 1989, retrospective data collection was updated from 1985 to 1988, and prospective data was collected from 1989 to the present. The data were collected according to the World Health Organization Diabetes Mondiale (DIAMOND) protocol. Primary ascertainment was based on personal interviews at schools, and secondary sources were pediatric hospitals and private diabetologists. RESULTS: The IDDM incidence per 10,000 children in the studied population was as follows: for 1985, 6.89; for 1986, 6.90; for 1987, 6.91; for 1988, 5.29; for 1989, 6.42; and for 1990, 7.59. Of those children, 51.7% reported previous infection or stress as a possible trigger factor. No sex preference, age incidence peak, or seasonal trend was found. CONCLUSIONS: The study documents an incidence rate of childhood IDDM in Avellaneda, Argentina, similar to other Occidental countries. PMID- 7988301 TI - Hypoglycemic activity of glyburide (glibenclamide) metabolites in humans. AB - OBJECTIVE: To assess the hypoglycemic effect and the insulin-releasing effect of the main glyburide (glibenclamide) metabolites 4-trans-hydroxy-glibenclamide (M1) and 3-cis-hydroxy-glibenclamide (M2) in humans. RESEARCH DESIGN AND METHODS: Eight healthy subjects participated in a placebo-controlled, randomized, single blind crossover study with five single-dose tests, 3 months apart: 3.5 mg glibenclamide (Gb) orally, 3.5 mg Gb intravenously, 3.5 mg M1 intravenously, 3.5 mg M2 intravenously, and placebo intravenously, each in the fasting state. Standardized meals were given 0.5 and 5.5 h after each medication. Blood glucose levels were measured by a glucose oxidase method, and serum insulin concentrations were analyzed by a specific immunoassay. RESULTS: Blood glucose levels during the first 5 h were significantly lowered not only by Gb but also by M1 and M2. The mean +/- SE blood glucose reductions (versus placebo) expressed as percent of area under the curve (AUC) (0-5 h) were 18.2 +/- 3.3% for M1, 12.5 +/- 2.3% for M2, 19.9 +/- 2.1% for intravenous Gb, and 23.8 +/- 1.2% for Gb orally. Serum insulin levels were significantly increased by Gb as well as by M1 and M2. and M2. CONCLUSIONS: The two main metabolites of glyburide (glibenclamide) have a hypoglycemic effect in humans, which is due to increased insulin secretion. PMID- 7988302 TI - Physical activity and fibrinogen concentration in newly diagnosed NIDDM. AB - OBJECTIVE: To evaluate whether plasma fibrinogen concentration is correlated with the level of physical activity and aerobic power in patients with newly diagnosed non-insulin-dependent diabetes mellitus (NIDDM). RESEARCH DESIGN AND METHODS: We studied 78 middle-aged (54 +/- 6 years, mean +/- SD), obese (body mass index [BMI] 32+/- 5 kg/m2) patients (45 men and 33 women) before and after a 12-month treatment period consisting of either conventional treatment given by community health centers or intensified dietary and exercise education given by a university outpatient clinic. Plasma fibrinogen concentration was measured by using a coagulometer. Physical activity was assessed by a questionnaire, and the patients were classified into a sedentary group or moderately or intensively exercising groups. Aerobic power (maximum oxygen uptake [VO2max], anaerobic threshold [VO2at]) was measured by direct breath-by-breath technique. RESULTS: At baseline, the sedentary patients had higher fibrinogen concentration than those with moderate or high physical activities (3.8 +/- 0.8 vs. 3.3 +/- 0.7 g/l, P < 0.01). Both VO2max and VO2at (ml.min-1.kg-1) showed an inverse linear correlation with fibrinogen (r = -0.38, P < or = 0.001, and r = -0.29, P < 0.01, respectively). In the stepwise multiple regression analysis, BMI, VO2 (ml/min), and smoking were the only significant independent factors explaining 23% of the variance in fibrinogen concentration. In sedentary patients, poor glycemic control was related with high fibrinogen concentration. During the follow-up period, patients maintained, on the average, good to moderate glycemic control. The originally sedentary group showed a decrease in fibrinogen concentration (to 3.3 +/- 0.7 g/l, P < or = 0.001) that reached the same level that the physically more active groups had at baseline. This change was associated with improved glycemic control, but not with any of the other assessed factors, including fatty acid composition of serum lipids reflecting dietary intake of fats. CONCLUSIONS: In addition to BMI and smoking, low reported physical activity and low aerobic power are independently associated with high plasma fibrinogen concentration in newly diagnosed NIDDM. PMID- 7988304 TI - Assessment of the DQB1-DQA1 complete genotype allows best prediction for IDDM. AB - OBJECTIVE: To analyze the HLA-DQ (human leukocyte antigen) genetic association with insulin-dependent diabetes mellitus (IDDM) patients of the Northeast Italian population. RESEARCH DESIGN AND METHODS: Fifty-one IDDM patients and 52 healthy control subjects were molecularly typed for DQB1 and DQA1 loci by using allele specific oligonucleotide probes and polymerase chain reaction amplified genomic DNA. DNA enzyme immunoassay was used to assess allele specificities. RESULTS: IDDM status strongly correlated with DQB1 alleles carrying a non-aspartic acid (non-Asp) residue in position 57 of DQ beta-chain and DQA1 alleles with an arginine (Arg) residue in position 52 of DQ alpha-chain. Individuals with two DQB1 (non-Asp) alleles and two DQA1(Arg) alleles had the highest relative risk for disease: they constituted approximately 40% of IDDM patients compared with 0% of control subjects. Heterozygosis at either residue 57 of DQB1 or residue 52 of DQA1 was sufficient to abrogate statistical significance for disease association, although 47% of IDDM patients were included in these two groups compared with 21% of normal control subjects. On the other hand, the presence of two DQB1 alleles with Asp in position 57 was sufficient to confer resistance to disease irrespective of the DQA1 genotype. CONCLUSIONS: The results demonstrate that the complete HLA-DQ genotype, more than a single DQB1 or DQA1 locus, should be determined to estimate the highest risk for disease. Screening a population for preventive purposes and/or early signs of IDDM should then take advantage of this result, and "susceptible homozygous" individuals should be followed very closely and considered the first group of choice for possible new therapeutic trials. PMID- 7988303 TI - Subcutaneous injection of the incretin hormone glucagon-like peptide 1 abolishes postprandial glycemia in NIDDM. AB - OBJECTIVE: To investigate the effect of subcutaneously injected glucagon-like peptide 1 (GLP-1) (7-36)amide on postprandial plasma glucose, insulin, and C peptide levels in patients with non-insulin-dependent diabetes mellitus (NIDDM) and a secondary failure to sulfonylureas. RESEARCH DESIGN AND METHODS: GLP-1 (25 nmol) was injected subcutaneously into either the abdominal wall or the gluteal region at a standardized depth and speed. The injection device was guided by the ultrasound determination of the depth of the fat layer. The peptide was given 5 min before a standard meal. Plasma concentrations of glucose, C-peptide, insulin, glucagon, and GLP-1 were followed during 240 min after the injection. RESULTS: In control experiments, a significant hyperglycemia was attained after the meal. GLP 1 given into the abdominal wall not only virtually abolished the post-prandial blood glucose rise but significantly decreased glucose concentrations, with a nadir at approximately 25 min after the injection. A rapid rise of C-peptide and insulin levels was observed 10-15 min after the injection of GLP-1. The stimulatory effect of GLP-1 was transient, and, at 45 min after the meal, both insulin and C-peptide levels were almost identical in GLP-1 and control experiments. Significantly lower glucagon concentrations were observed 35-65 min after the peptide injection. GLP-1 concentration in plasma increased from 10 pM to a peak concentration (Cmax) of 70 pM at Tmax 30 min after injection. Then GLP 1 levels rapidly decreased to 25 pM at 95 min and returned to basal at 215 min. The gluteal injection of GLP-1 had similar effects compared with the abdominal administration on plasma levels of glucose, insulin, C-peptide, and glucagon. CONCLUSIONS: GLP-1 is promptly absorbed from the subcutaneous tissue. It exerts a significant blood glucose lowering effect when administered before meals in overweight patients with NIDDM. PMID- 7988305 TI - How does provider and patient awareness of high-risk status for lower-extremity amputation influence foot-care practice? AB - OBJECTIVE: To assess whether patients with diabetes at high risk for lower extremity amputation received more intensive medical care or self-care instruction and to determine the association between foot care and risk of lower extremity amputation. RESEARCH DESIGN AND METHODS: Patients with diabetes were seen at he Seattle Veterans Affairs Medical Center (VAMC) between October 1984 and April 1987; 67 patients were seen for initial non-traumatic amputation, and 236 consecutive control subjects were seen for non-traumatic but medically necessary surgery unrelated to diabetes. Data collection included patient interview and medical record review. High-risk status, defined as presence of peripheral neuropathy, peripheral vascular disease, or or prior foot ulcer, was temporally fixed at 2 years before study enrollment. RESULTS: Peripheral neuropathy, peripheral vascular disease, and prior foot ulcer were independently associated with risk of lower-extremity amputation: peripheral neuropathy odds ratio (OR) = 1.4 (95% confidence interval (CI) 0.7-2.7), peripheral vascular disease OR = 2.6 (95% CI 1.5-4.5), and prior foot ulcer OR = 10.9 (95% CI 4.6 25.5). Patients with a prior foot ulcer were significantly more likely to have seen a podiatrist and to have received outpatient diabetes education at the Seattle VAMC; their providers were more likely to prescribe clipping toenails, regular foot washing, and elevating feet during the day (chi 1(2) for proportions P < 0.05). However, for patients with a history of peripheral neuropathy or peripheral vascular disease, there was no statistically significant increase in medical care (podiatry visits, outpatient diabetes education) or self-care instruction (clip nails, elevate feet, or self-monitor blood glucose) compared with patients without either of these two conditions (chi 1(2) for proportions P > 0.20). CONCLUSIONS: When clinicians were aware of a patient's very elevated risk for lower-extremity amputation (evidenced by prior history of foot ulcer), they were more likely to prescribe preventive foot-care behaviors, but awareness of other risk factors (peripheral neuropathy or peripheral vascular disease) did not necessarily increase preventive care. Physicians and patients should receive periodic education and reinforcement of diabetes management skills to modify care delivered to individuals at highest risk for lower-extremity amputation. PMID- 7988306 TI - A population survey on the prevalence of diabetes in Kin-Hu, Kinmen. AB - OBJECTIVE: To investigate the prevalence of non-insulin-dependent-diabetes mellitus in Kin-Hu, Kinmen. RESEARCH DESIGN AND METHODS: This is a community based population survey. The target population are residents > or = 30 years of age in Kin-Hu, Kinmen, according to the official household registry in 1990. Face to face interviews were conducted by the Yang-Ming Crusade in 1991 using a structured questionnaire. Fasting blood samples were drawn by public health nurses, and a 75-g oral glucose tolerance test was performed for definite diagnosis of diabetes. RESULTS: There were 4,097 eligible subjects (2,026 men and 2,071 women), and 3,236 had complete fasting plasma glucose data (1,536 men and 1,700 women). The response rate was 79% (76% for men and 82% for women). The age specific response rates were 81% for the 30- to 39-year and 50- to 59-year age groups, 84% for the 40- to 49-year age-group, and 69% for the > or = 60-year age group. The crude prevalence of diabetes in Kin-Hu was 6.5% (2.0% previous and 4.5% new). With the standard world population of Segi, the age-adjusted prevalence rate was 4.9% (4.5% for men and 5.4% for women). The prevalence rate of diabetes increased significantly with age. The prevalence of previously diagnosed diabetes accounted for less than one third of the total rate. CONCLUSIONS: The population survey in Kin-Hu, Kinmen, had a high response rate of 79%. The crude prevalence rate of diabetes was 6.5%, and the age-adjusted prevalence rate was 4.9%. The low ratio of previously diagnosed to newly diagnosed diabetic cases may be due to lack of public awareness and medical services in this community. PMID- 7988308 TI - Coronary heart disease mortality is actually low in diabetic Japanese by direct comparison with the Joslin cohort. AB - OBJECTIVE: To identify the mortality rate from coronary heart disease (CHD) in diabetic Japanese by directly comparing the Tokyo University Hospital cohort and the Joslin cohort using identical protocols. RESEARCH DESIGN AND METHODS: Five hundred thirty-eight diabetic patients who were treated at Tokyo University Hospital with a 35- to 62-year age range at entry and with a diabetes duration of < 5 years were followed retrospectively for more than 24 years. RESULTS: The percentage of patients who survived at the end of the 24-year period was higher in the Tokyo University cohort (42%) than in the Joslin cohort (12%). The percentage of patients who died from CHD was remarkably lower in the Tokyo University cohort (11%) than in the Joslin cohort (39%). The CHD mortality rate was lower in the Tokyo University cohort than in the Joslin cohort, regardless of the duration of diabetes. CONCLUSIONS: Our study confirmed the previous finding that the CHD mortality is lower in diabetic Japanese than in diabetic Caucasians. PMID- 7988307 TI - Different change in lipoprotein(a) levels from lipid levels of other lipoproteins with improved glycemic control in patients with NIDDM. AB - OBJECTIVE: To evaluate change both in lipoprotein(a) [Lp(a)] and lipid levels in other lipoproteins in non-insulin-dependent diabetes mellitus (NIDDM) after short term improvement of glycemic control. RESEARCH DESIGN AND METHODS: We compared Lp(a) levels in 210 NIDDM patients with those in 46 control subjects and evaluated the relationship between glycemic control and Lp(a) levels in diabetic patients. In addition, changes in Lp(a) levels and lipid levels were assessed after the improvement of glycemic control in 54 poorly controlled NIDDM patients. RESULTS: In NIDDM, Lp(a) levels in all patients, 62 patients with HbA1c < 6.0%, and 75 patients with HbA1c between 6.0 and 8.0%, were significantly higher than those in control subjects (19.1 [1.7-106.6], 19.2 [6.0-106.6], and 20.3 [2.7 75.3] vs. 15.4 [2.0-61.7] mg/dl, median [range], P < 0.05). Lp(a) levels in 73 patients with HbA1c of > or = 8.0% (18.7 [1.7-58.8] mg/dl) were not significantly different from those in control subjects. After glycemic control, lipid levels in plasma and in other lipoproteins fell significantly, but Lp(a) did not change (from 18.3 [1.7-58.8] to 18.4 [6.6-95.3] mg/dl). Changes in lipid levels, including Lp(a), did not correlate with those in fasting plasma glucose or HbA1c. CONCLUSIONS: These results suggest that elevated Lp(a) levels do not reflect poor glycemic control and that Lp(a) levels are independent of lipid levels in other lipoproteins after improved glycemic control in NIDDM. PMID- 7988309 TI - Complications of the pump pocket may represent a significant cause of incidents with implanted systems for intraperitoneal insulin delivery. AB - OBJECTIVE: To increase awareness of adverse events associated with the use of programmable implantable pumps (PIPs). CASES: There were 7 cases of complications associated with the pump-pocket among 40 patients treated by PIP, and we searched for risk factors. RESULTS: Seven of 40 type I diabetic patients treated by PIP presented severe complications of the pump-pocket, resulting in five definitive explanations and nine other surgical interventions. The lesions included an exudative reaction in the pump-pocket and a skin retraction or atrophy, which were complicated by skin erosion in five patients. Coagulase-negative staphylococcus was identified in the pump-pocket in four patients, including three cases of skin erosion. No specific risk of local complications could be attributed to age, sex, duration of diabetes, body mass index, presence of retinopathy or peripheral neuropathy, HbA1c level since implantation, depth of implantation in the abdominal wall, or duration of experience with PIP. Usual physical activity corresponding to > 2,000 kcal energy expenditure per week, estimated by a questionnaire, appeared to be the only identified significant risk factor. CONCLUSIONS: From these results, we suggest that physical activity should be limited to moderate exercise and exclude vigorous efforts in diabetic patients treated by PIP to avoid an increased risk of complications at the implantation site. PMID- 7988310 TI - Effects of a traditional lifestyle on obesity in Pima Indians. AB - OBJECTIVE: The Pima Indians of Arizona have the highest reported prevalences of obesity and non-insulin-dependent diabetes mellitus (NIDDM). In parallel with abrupt changes in lifestyle, these prevalences in Arizona Pimas have increased to epidemic proportions during the past decades. To assess the possible impact of the environment on the prevalences of obesity and NIDDM, data were collected on members of a population of Pima ancestry (separation 700-1,000 years ago) living in a remote mountainous location in northwestern Mexico, with a lifestyle contrasting markedly with that in Arizona. RESEARCH DESIGN AND METHODS: Pima heritage was established by history and by use of Pima language. Measurements of weight, height, body fat (bioimpedance), blood pressure, plasma levels of glucose, cholesterol, and HbA1c were obtained in 19 women (36 +/- 13 years of age) and 16 men (48 +/- 14 years of age) and compared with sex-, age- and diabetes status-matched Pimas living in Arizona (10 Arizona Pimas for each Mexican Pima). RESULTS: Mexican Pimas were lighter (64.2 +/- 13.9 vs. 90.2 +/- 21.1 kg, P < 0.0001; means +/- SD) and shorter (160 +/- 8 vs. 164 +/- 8 cm, P < 0.01) with lower body mass indexes (24.9 +/- 4.0 vs. 33.4 +/- 7.5 kg/m2, P < 0.0001) and lower plasma total cholesterol levels (146 +/- 30 vs. 174 +/- 31 mg/dl, P < 0.0001) than Arizona Pimas. Only two women (11%) and one man (6%) had NIDDM, contrasting with the expected prevalences of 37 and 54% in female and male Arizona Pimas, respectively. CONCLUSIONS: This preliminary investigation shows that obesity, and perhaps NIDDM, is less prevalent among people of Pima heritage living a "traditional" lifestyle than among Pimas living in an "affluent" environment. These findings suggest that, despite a similar potential genetic predisposition to these conditions, a traditional lifestyle, characterized by a diet including less animal fat and more complex carbohydrates and by greater energy expenditure in physical labor, may protect against the development of cardiovascular disease risk factors, obesity, and NIDDM. PMID- 7988311 TI - Frequency of depression in IDDM patients in Greece. PMID- 7988312 TI - Lipoprotein(a) and insulin treatment in NIDDM patients. PMID- 7988313 TI - Repeated vertebral compression fractures during hypoglycemia unawareness. PMID- 7988314 TI - The American Diabetes Association annual meeting, 1994: treatment issues for NIDDM. PMID- 7988315 TI - Epidemiology of IDDM in Switzerland. Increasing incidence rate and rural-urban differences in Swiss men born 1948-1972. AB - OBJECTIVE: To determine the incidence of insulin-dependent diabetes mellitus (IDDM) in Switzerland by undertaking a retrospective analysis of the registry of the Swiss army, which contains updated medical files for all male Swiss citizens. Nation-wide data for IDDM epidemiology have not been available in Switzerland. RESEARCH DESIGN AND METHODS: Every male Swiss citizen is obliged to enlist in the Swiss military service at 19 years of age, when a personal, continuously updated medical file is established. Diabetes is an exclusion condition for military service and is clearly marked in the file. A total number of 514,747 files, corresponding to birth year cohorts 1948-1950, 1955-1957, 1962-1964, and 1970 1972, have been manually checked for the diagnosis of IDDM. RESULTS: IDDM was identified in 926 cases in the four groups of three age-cohorts. The incidence at < or = 15 years (per 100,000/year) was 4.5 in the age cohorts 1948-1950 and 7.2 in the age cohorts 1970-1972 (P < 0.005). An additive age-cohort Poisson regression model fits the nationwide incidences adequately, neither a period effect nor age x cohort interactions being required. In the oldest age cohorts, the age-specific incidence of IDDM was calculated up to the age of 43 and was approximately 7/100,000/year in men between 20 and 40. In these age cohorts, we found an approximately 50% higher risk to develop IDDM at age < or = 19 for men living in an urban region and a significantly (P < 0.005) increased incidence between 20 and 40 years in rural regions compared with urban regions. CONCLUSIONS: The incidence of IDDM in Switzerland is comparable to other countries in central Europe and has been increasing in the last 20 years. This is in accordance to most recent epidemiological studies worldwide. In addition, the data suggest exogenous factors inducing IDDM at a younger age in urban regions. PMID- 7988316 TI - Obesity, fat distribution, and weight gain as risk factors for clinical diabetes in men. AB - OBJECTIVE: To investigate the relation between obesity, fat distribution, and weight gain through adulthood and the risk of non-insulin-dependent diabetes mellitus (NIDDM). RESEARCH DESIGN AND METHODS: We analyzed data from a cohort of 51,529 U.S. male health professionals, 40-75 years of age in 1986, who completed biennial questionnaires sent out in 1986, 1988, 1990, and 1992. During 5 years of follow-up (1987-1992), 272 cases of NIDDM were diagnosed among men without a history of diabetes, heart disease, and cancer in 1986 and who provided complete health information. Relative risks (RRs) associated with different anthropometric measures were calculated controlling for age, and multivariate RRs were calculated controlling for smoking, family history of diabetes, and age. RESULTS: We found a strong positive association between overall obesity as measured by body mass index (BMI) and risk of diabetes. Men with a BMI of > or = 35 kg/m2 had a multivariate RR of 42.1 (95% confidence interval [CI] 22.0-80.6) compared with men with a BMI < 23.0 kg/m2. BMI at age 21 and absolute weight gain throughout adulthood were also significant independent risk factors for diabetes. Fat distribution, measured by waist-to-hip ratio (WHR), was a good predictor of diabetes only among the top 5%, while waist circumference was positively associated with the risk of diabetes among the top 20% of the cohort. CONCLUSIONS: These data suggest that waist circumference may be a better indicator than WHR of the relationship between abdominal adiposity and risk of diabetes. Although early obesity, absolute weight gain throughout adulthood, and waist circumference were good predictors of diabetes, attained BMI was the dominant risk factor for NIDDM; even men of average relative weight had significantly elevated RRs. PMID- 7988318 TI - Erythrocyte sodium-lithium countertransport activity as a marker of predisposition to hypertension and diabetic nephropathy in NIDDM. AB - OBJECTIVE: To evaluate the potentiality of erythrocyte sodium-lithium countertransport activity (SLC) as a marker of predisposition to hypertension and diabetic nephropathy in non-insulin-dependent diabetes mellitus (NIDDM). RESEARCH DESIGN AND METHODS: We examined 96 patients with NIDDM and 26 healthy control subjects. SLC and other data were compared among subgroups of the patients classified on the basis of hypertension, family history of hypertension, and stages of nephropathy. Data were also analyzed by stepwise multiple regression analyses. RESULTS: SLC was significantly higher in patients with hypertension than in those with normotension and significantly higher in patients with a positive family history of hypertension than in the negative group. Further analysis revealed that a family history of hypertension has independent influence on SLC, but hypertension itself does not. SLC was significantly higher in patients with macroalbuminuria than with microalbuminuria and higher in patients with microalbuminuria than with normalbuminuria. In stepwise multiple regression analyses, a family history of hypertension was the most important determinant of SLC, and SLC was the most important determinant of nephropathy. CONCLUSIONS: These data suggest that SLC strongly reflects a predisposition to hypertension and that it can be a useful marker of diabetic nephropathy in NIDDM. PMID- 7988317 TI - Children with newly diagnosed IDDM have increased levels of antibodies to bovine serum albumin but not to ovalbumin. Childhood Diabetes in Finland Study Group. AB - OBJECTIVE: To study the humoral immune response to bovine serum albumin (BSA) and ovalbumin (OA) in children with newly diagnosed insulin-dependent diabetes mellitus (IDDM). RESEARCH DESIGN AND METHODS: We examined serum samples from 505 children 0.8-14.9 years of age with newly diagnosed IDDM for antibodies to BSA and OA by enzyme-linked immunosorbent assay (ELISA). We also had two control groups: 85 unrelated control children (0.8-7.1 years of age) and 395 nondiabetic siblings (3.0-14.9 years of age). The specificity of antibodies detected in ELISA was confirmed by immunoblotting in a subset of sera with varying levels of antibodies. RESULTS: Diabetic children < 7 years of age had a significantly higher level of IgG (immunoglobulin) antibodies to BSA than did unrelated control children (P < 0.0001). The difference was greatest in the youngest group of children, 0.8-2.9 years of age. IgA antibodies to BSA were detected more frequently among diabetic than control children (P = 0.0009). Levels of IgG and IgA antibodies to ovalbumin did not differ between diabetic and control children. Diabetic children 3.0-14.9 years of age also had higher levels of IgG and IgA antibodies to BSA than did their age- and sex-matched nondiabetic siblings (P = 0.02 and P < 0.0001, respectively). Those siblings who contracted IDDM during the follow-up period (n = 15) had a measurable level of IgA antibodies to BSA more often than did those who remained nondiabetic (60 and 34%, respectively; P = 0.04). Neither before nor after diagnosis of IDDM was there any significant trend in antibody levels. CONCLUSIONS: A high level of antibodies to BSA commonly associates with IDDM, whereas the humoral immune response to OA is similar in diabetic and nondiabetic children. PMID- 7988319 TI - Maximizing foot salvage by a combined approach to foot ischemia and neuropathic ulceration in patients with diabetes. A 5-year experience. AB - OBJECTIVE: The combination of peripheral neuropathy and arterial insufficiency in patients with diabetes frequently results in chronic non-healing foot ulcers. These patients often have a protracted course that commonly ends in limb amputation. RESEARCH DESIGN AND METHODS: Since 1987, 39 diabetic patients presented with 42 neuropathic ulcerations beneath the lesser metatarsal heads, complicated by severe arterial insufficiency. A variety of vascular reconstructions were performed to improve circulation to the foot. After successful vascular reconstruction, 14 patients with deep ulcers underwent resection of the involved bone or joint through a plantar elliptical incision with excision of the ulcer and primary closure (33%). Five patients required a simultaneous panmetatarsal head resection (12%). For fifteen superficial ulcers, metatarsal osteotomy through a dorsal approach was performed (36%). Eight patients underwent a fifth metatarsal head resection through a dorsal approach (19%). RESULTS: In follow-up of 2-64 months (mean 21.2 months), 35 extremities with patent bypass grafts achieved and maintained primary healing of their local foot procedure (83%). Two feet required subsequent revision but ultimately healed (5%). Three feet (7%) developed a new plantar ulceration adjacent to the original one. In two extremities, the foot remained healed in spite of thrombosis of their grafts (5%). One patient with a thrombosed graft required a below-knee amputation. One patient died before the foot healed with a patent bypass graft. Overall, 40 of 42 extremities (95%) ultimately healed over the course of the follow-up period. CONCLUSIONS: We conclude that complex neuropathic ulcers in diabetic patients can be successfully treated by an aggressive surgical approach that removes infected bone and ulcers and corrects underlying structural abnormalities provided arterial insufficiency is corrected first. PMID- 7988320 TI - Anti-insulin antibodies are a cause of hypoglycemia following pancreas transplantation. AB - OBJECTIVE: Hypoglycemic symptoms have been reported by more than half of pancreas transplantation (PTX) recipients. To better understand the mechanism for the hypoglycemia documented in some of these patients, we studied the glucose and pancreatic hormone response to Sustacal in patients with and without hypoglycemia following PTX. RESEARCH DESIGN AND METHODS: Twelve patients with established, repeated episodes of hypoglycemia following PTX (hypo) were case-matched to PTX recipients without hypoglycemic symptoms (control; n = 7). On the day of the study, fasting glucose, free and total immunoreactive insulin (IRI), C-peptide, proinsulin, and glucagon were drawn (time 0); Sustacal was administered; and glucose, free and total IRI, and C-peptide were assayed at 15, 30, 45, 75, 120, 150, 180, and 240 min. Based on the glucose response to Sustacal, the hypo group was further divided into those whose glucose rose after Sustacal (hypo-high; n = 7) and those with no increase in glucose from baseline concentration (hypo-flat; n = 5). RESULTS: Before the administration of Sustacal, the hypo-high group had a lower fasting free/total IRI (0.26 +/- 0.06, mean +/- SE) than the hypo-flat (0.51 +/- 0.02) or control (0.52 +/- 0.04) groups (both P < 0.05 compared with hypo-high). The glucose response to Sustacal was greatest in the hypo-high group as defined. Area under the curve (AUC) for total IRI following Sustacal was also greatest in the hypo-high group (P < 0.05 compared with both control and hypo flat groups), but there was no significant difference in free IRI AUC following Sustacal between the three groups. Two individuals developed hypoglycemia during the Sustacal challenge, both in the hypo-high group. CONCLUSIONS: The lower fasting free/total IRI ratio and greater increase in glucose and total IRI in response to Sustacal in the hypo-high group compared with either the hypo-flat or control groups are consistent with the presence of significant quantities of anti insulin antibodies in the hypo-high group. Because anti-insulin antibodies are, in turn, an established cause of episodic hypoglycemia, this study provides the first data to support the hypothesis that significant quantities of anti-insulin antibodies are a cause of symptomatic hypoglycemia following PTX in some recipients. PMID- 7988321 TI - Structure and correlates of diabetes-specific locus of control. AB - OBJECTIVE: To examine the structure and correlates of diabetes-specific locus of control. RESEARCH DESIGN AND METHODS: Study participants were 165 adult patients from a comprehensive outpatient diabetes education program who completed a research protocol at the outset of the program. The protocol included measures of diabetes locus of control (DLC), glycemic control, self-care behavior, and emotional well-being. RESULTS: Scales measuring internal and powerful other DLC each had two components. One component of internal DLC, autonomy, was significantly associated with positive outcomes, and the other component, self blame, was related to negative outcomes. The two components of powerful other DLC were differently correlated with various aspects of strict regimen adherence, and chance DLC was associated with a variety of measures reflecting a pattern of dysfunction. CONCLUSIONS: The concept of DLC appears to have explanatory power in accounting for health outcomes, especially when internal DLC measures of autonomy and self-blame are differentiated. It is important to find educational interventions that work effectively with patients who believe that health outcomes are controlled by chance, because they seem to be at special risk for health-related problems. PMID- 7988322 TI - Evaluating unplanned endotracheal extubations. AB - Unplanned extubation is a complication of endotracheal intubation that occurs despite close patient monitoring in the intensive care unit. The authors describe one method of analyzing unplanned extubations that critical care nurses can use to determine the quality of care provided. This method uses a data collection tool that focuses on incidence of unplanned extubation, structure, process and outcome as indicators of quality of care. This article will help you identify patient characteristics that determine if a particular patient population is at greater risk for unplanned extubations. PMID- 7988323 TI - Nursing assessment of portable AP chest x-rays. AB - Daily portable chest x-rays are often used to monitor the status of patients in a critical care unit. Routine nursing monitoring and assessment of these patients and their x-rays contribute to the patient's successful outcome. This article discusses a systematic nursing approach to evaluating portable anterior-posterior (AP) chest x-rays. When a chest x-ray is taken in the critical care unit, as it is for many ICU patients, the nurse is in a unique position to assess the patient and implement emergency measures if x-ray results show incorrect placement of the endotracheal tube or any other lines. PMID- 7988324 TI - The brain-dead pregnant woman: finding meaning to help cope. AB - Caring for brain-dead pregnant women is a new critical care challenge. Rather than the usual life/death situations involving catastrophic events, critical care nurses have the added burden of caring for a life in suspension to maintain the viability of the fetus. Nurses struggle with keeping the brain-dead patient alive and yet know that as soon as the infant is delivered the mother will be allowed to die. These authors use interviews with clinical nurses to show how they used the coping strategy of creating meaning to successfully cope with this difficult situation. PMID- 7988325 TI - Clinical viewpoints: clinical care nurses share how they cope with caring for the brain-dead pregnant woman. PMID- 7988326 TI - Treatments not specifically listed in the living will: the ethical dilemmas. AB - Because of publicity regarding living wills and laws on required request, the number of patients with them has increased. Consequently, related ethical dilemmas are also becoming more common. One example of such an ethical dilemma occurs when a living will fails to describe the current patient situation. The following case illustrates this type of problem, one which critical care nurses are likely to encounter more often over the next few years. PMID- 7988327 TI - Preparing children for visiting parents in the adult ICU. AB - The issue of pediatric visitation in the adult ICU is a controversial one that often evokes strong opinions from critical care nurses. This author describes age related preparation strategies and nursing actions which are successful in providing a positive experience for the child, parent, and nurse. PMID- 7988329 TI - Neuro-invasive monitoring: the nurse's dynamic decision-making role. PMID- 7988328 TI - Practical tips from clinical nurses: opinions about children visiting. AB - Children visiting parents in the ICU is still controversial. Here are six different opinions about children visiting from ICU nurses, an infection control practitioner, and even a parent. All view points are important to consider in providing access of children to their critically ill parents. Interestingly, even nurses who do not generally support child visitation have allowed children's visits in special circumstances and found the experience positive. PMID- 7988331 TI - Adenosine thallium imaging: pharmacodynamics and patient monitoring. AB - Because many critical care patients have cardiac, trauma, or other complications that rule out usual exercise cardiac stress testing, the new use of adenosine for thallium imaging may be used for these patients. Because of its vasodilating properties, adenosine can be combined with thallium imaging to determine the presence of coronary artery disease in persons unable to exercise. This author describes the pharmacodynamics of adenosine, the process of thallium imaging, and the interpretation of the images which help the nurse prepare the patient and prevent complications. PMID- 7988330 TI - Differentiating ischemia, injury, infarction: expanding the 12-lead electrocardiogram. AB - In 50% of cases of myocardial infarction, the 12-lead electrocardiogram (ECG) is not diagnostic of the infarction. Critical care nurses, aware of subtle ECG changes coupled with patient complaint of chest pain, may improve recognition of myocardial infarction. Expanding the 12-lead ECG to include right ventricular precordial leads and posterior chest leads facilitates recognition of right ventricular infarction and posterior wall infarction not recognized on the standard 12-lead ECG. PMID- 7988332 TI - Factors related to length of ICU stay for CABG patients. AB - The investigator identified five factors related to ICU length of stay in patients who undergo coronary artery bypass grafting. This article describes these factors and suggests nursing interventions aimed at reducing the influence of these factors on patient length of stay. Some of the factors related to longer stays such as a Friday surgery day may surprise you, while factors related to shorter stays such as patient teaching will support your viewpoints on the value of bedside teaching. PMID- 7988333 TI - Nurse inventors: turning ideas into products. AB - Nurses develop innovative product ideas because they see the need and know how the product will actually be used in practice. However, identifying a practice dilemma and inventing a product to address the dilemma is just the first step in product development whether you take control of the entire process or collaborate with a company. PMID- 7988334 TI - Discharge teaching for the directional coronary atherectomy patient. AB - Due to the short length of stay for directional coronary atherectomy (DCA) patients, critical care nurses play a vital role in providing patients with discharge teaching. Decreased length of stay has left very little time for teaching DCA patients. It is critical for nurses to focus on key points and use concepts and words the patient immediately understands. This article describes key teaching strategies and provides sample written discharge teaching sheets for use in discharge teaching of the DCA patient. PMID- 7988335 TI - Holistic care of the critically ill: meeting both patient and family needs. AB - Holistic care of the critically ill includes meeting the needs of both the patient and the patient's family. The critical care nurse needs to be prepared to deal with the family's special needs during a time of crisis, including making decisions about the withdrawal of life support. This article addresses such issues, and includes care of the family once technological support has been withdrawn and the patient is transferred from the Intensive Care Unit. PMID- 7988336 TI - Preparing for cardiomyoplasty: a new horizon in cardiac surgery. AB - The number of patients with end-stage heart failure is rapidly increasing and traditional therapies are not able to effectively meet the demand. The health care profession continues to search for innovative alternative treatments and dynamic cardiomyoplasty is viewed as an option for patients in this population. Now this procedure is being offered through clinical trials at five sites in the United States, but this number will increase and nurses across the country will want to prepare to care for patients with this interesting and unusual procedure. PMID- 7988337 TI - Transcranial Doppler: advanced technology for assessing cerebral hemodynamics. AB - Transcranial Doppler (TCD) is an expanding noninvasive technology used in a wide array of patients with altered neurological states for assessing cerebral hemodynamic status. The critical care nurse who is familiar with the principles of TCD can assist with the procedure and assessment of results. Including the TCD results with her or his other neurological assessment data will identify the first signs of cranial circulatory changes and improve patient outcome. PMID- 7988338 TI - Synchronous independent lung ventilation. AB - Ventilated patients with unilateral lung disease present a unique challenge because each lung requires independent FiO2, PEEP, and mode settings. With early implementation of Synchronous Independent Lung Ventilation, each lung is treated individually and chances for survival may increase. Critical care nurses face new challenges in assessing and preventing complications for these patients. PMID- 7988339 TI - Oxygen radicals and calcium ion flux: role in reperfusion injury following AMI. AB - Occlusion of coronary vessels is now frequently treated by reperfusion using thrombolytics, angioplasty, or coronary artery bypass surgery. On reperfusion, however, acutely ischemic cells may be damaged by the action of oxygen radicals on cell membranes, and by calcium ion flux. By understanding the mechanisms behind reperfusion injury, the critical care nurse can assess and plan for actual and potential patient care problems. PMID- 7988340 TI - Designing a product evaluation project using research principles. AB - Critical care nurses are frequently involved in the evaluation of products used to enhance patient care. The authors discuss how research principles can be incorporated into the design for product evaluation to provide reliable information for purchasing decisions and add to the existing body of nursing knowledge. Because of the increasing number of products available to critical care nurses, the authors describe how to use research principles to design a product evaluation study for several examples. PMID- 7988341 TI - Anxiety during critical illness of a family member. AB - Critical care nurses know that some families handle the anxiety of the critical illness well and can continue to learn and problem-solve, while others seem to be overwhelmed with the anxiety and are unable to function. The way families handle the anxiety are important to their ability to learn. With shorter stays, the nurse needs to help families to handle their anxiety, so they can prepare for the patient's ultimate discharge home. The author describes results of a study on the variables related to family member anxiety and techniques for assessment and reduction of family anxiety. PMID- 7988342 TI - Peripheral arterial disease. AB - Peripheral arterial diseases are common problems because atherosclerosis, the most common cause of both occlusive peripheral arterial disease and aneurysmal disease, is a feature of an aging population. The less common types of occlusive peripheral arterial disease--the vasospastic disorders and the arteritides- although frequently not addressed to any extent in medical school curricula or in residency programs in family and internal medicine, offer the alert and informed clinician diagnostic and therapeutic opportunities that are too important to neglect. As a group, abnormalities of the peripheral arteries are easy to detect if careful observation and examination of the extremities is included in the physical examination and attention to functional disorders is included in the medical history. In this presentation, the clinical features, physical findings, complications, useful noninvasive diagnostic tests, imaging techniques, and therapeutic options for atherosclerotic occlusive peripheral arterial disease (both chronic and acute), uncommon types of occlusive arterial disease of both the lower and upper extremities, the vasospastic disorders, and the peripheral arterial presentations of the arteritides are reviewed. The application of natural history and comorbidity of a particular arterial disease, when available, is emphasized in the formulation of management for the individual patient. PMID- 7988343 TI - Endothelin-1 and big endothelin-1 in NIDDM patients with and without microangiopathy. AB - To examine a possible role for endothelin-1 in the pathophysiology of diabetic microangiopathy, we measured plasma levels of endothelin-1 and big endothelin-1, a precursor peptide of endothelin-1, in 33 untreated patients with non-insulin dependent diabetes mellitus. There was no significant difference among the mean plasma endothelin-1 concentrations in 18 patients with microangiopathy, in 15 patients without microangiopathy and in 33 age-matched normal subjects. In contrast, the mean plasma big endothelin-1 concentration in patients with microangiopathy was significantly higher than in those without microangiopathy or in normal subjects. As a consequence, the mean big endothelin-1 to endothelin-1 ratio in patients with microangiopathy was significantly higher than in the other two groups. There was no significant correlation between plasma levels of endothelin-1 or big endothelin-1 and fasting blood glucose, HbA1c, mean blood pressure, or period of duration of diabetes mellitus in the patient groups. The results indicate that elevation of plasma big endothelin-1 levels with diminished conversion of big endothelin-1 to endothelin-1 is associated with diabetic microangiopathy, which may be the effect rather than the cause of endothelial dysfunction. PMID- 7988344 TI - Natural history of B-cell dysfunction in spontaneously diabetic Chinese hamsters. AB - To elucidate the pathogenesis of diabetes in spontaneously diabetic Chinese hamsters (CHAD strain), a longitudinal study from just after weaning to overt diabetic state was performed. Fasting and non-fasting plasma glucose, non-fasting plasma insulin and pancreatic hormone contents (insulin, glucagon and amylin) were measured, and light microscopic examination of pancreatic islets by immunohistochemical technique and pancreas perfusion study were performed. No insulitis was found in the islets of the CHAD strain. In animals aged 1 month, there was no significant difference in the percentage of B-cell area to islet area between the CHAD strain and the control. At this stage, hyperinsulinemia was observed despite normal plasma glucose levels both in fasting and non-fasting states. In the animals of the CHAD strain aged 2-4 months, insulin secretion from the pancreas, pancreatic insulin content and non-fasting plasma insulin level decreased in proportion to the decrease of B-cell mass. In animals aged about ten months, severe hyperglycemia and hypoinsulinemia were observed. We demonstrated the existence of amylin-like immunoreactivity in the B-cells of Chinese hamsters. However, no amyloid deposit was observed in the islets of the CHAD strain. After the onset of diabetes, amylin secretion from the pancreas and pancreatic amylin content in the CHAD strain were significantly lower than those in the control. We demonstrated the natural history of B-cell dysfunction in the CHAD strain. It could mean the process of B-cell exhaustion. The profile of the CHAD strain is similar to some types of human NIDDM. Therefore, the CHAD strain is a useful diabetic model in the study of NIDDM. PMID- 7988345 TI - Gliclazide directly suppresses arginine-induced glucagon secretion. AB - To clarify whether the effect of sulfonylurea on glucagon secretion is directly on the pancreatic A cell, we examined changes produced by gliclazide in glucagon (IRG), insulin (IRI) and somatostatin (IRS) release from the isolated perfused rat pancreas. Under 5 mM glucose infusion, IRI and IRS were increased by gliclazide in a dose-dependent manner, but IRG was unchanged. When 20 mM arginine was infused to stimulate glucagon secretion, both IRI and IRG increased markedly in a biphasic fashion and IRS increased slightly. The administration of gliclazide at the time of second phase response of IRG, IRI and IRS increased further and IRG decreased at every dose used. Insulin administration to the control and streptozotocin-treated rat pancreas did not change arginine-induced IRG secretion. Gliclazide-induced glucagon suppression was also observed in streptozotocin-diabetic rat pancreas. The amount of administered somatostatin required for inhibiting glucagon secretion was higher than the maximal level obtained from endogenous secretion of somatostatin after gliclazide. Neither cysteamine treatment alone (somatostatin-depleted) nor combined with streptozotocin-treatment (combined depletion of somatostatin and insulin) changed gliclazide-induced glucagon suppression. Thus, it is concluded that suppression of glucagon is induced by sulfonylurea itself. PMID- 7988346 TI - Birth size and risk of insulin-dependent diabetes mellitus (IDDM). AB - A case-control study was conducted to test the hypotheses that birth size is increased in infants who develop IDDM in childhood and that birth size differs by diagnosis age. Cases were non-Hispanic white (NHW) children randomly selected from the Colorado IDDM Registry (n = 221). Controls (n = 197) were NHW children frequency-matched to cases by age-group and gender. Self-administered questionnaires collected birth size and demographic data. There were no significant univariate differences in birth weight (cases 3303.0 g; controls, 3346.1 g; P = 0.40), birth length (cases, 50.8 cm; controls, 51.2 cm; P = 0.28), or ponderal index (cases, 2.52; controls, 2.49; P = 0.92). The case/control odds ratio (OR) controlling for gender, maternal education, and birth place was 1.0 (95% confidence interval (CI) 0.4, 2.5) for the highest category of birth weight compared to the lowest. There were no statistically significant case/control differences in ponderal index (highest to lowest category OR = 1.1; 95% CI 0.6, 2.0) or birth length (1 cm increase OR, 1.0; 95% CI 0.9, 1.2). Similarly, analysis by age-at-diagnosis groups revealed no significant differences, suggesting that birth size does not reveal prenatal diabetogenic influences. PMID- 7988347 TI - The effect of pancreatic elastase on diabetic nephropathy. AB - Pancreatic elastase has been shown to inhibit the thickening of glomerular basement membranes in experimental diabetic animals. We explored the clinical significance of the prolonged administration of pancreatic elastase on diabetic nephropathy, in patients whose blood glucose levels and blood pressure were controlled. Pancreatic elastase was administered for 12 months. Body weight levels, blood glucose levels, HbA1c values and blood pressure remained unchanged. Administration of 10,800 U of pancreatic elastase caused a significant decrease in albuminuria (before administration, 512.4 +/- 79.8 mg/g creatinine vs. 12 months after administration, 284.1 +/- 61.9 mg/g creatinine, P < 0.01, n = 28). In the contrast group (n = 18), no significant changes in albuminuria were observed after administration of 300 mg of dilazep dihydrochloride. Serum levels of creatinine and urinary levels of NAG and beta 2 MG were not affected by pancreatic elastase. The present study indicates a significant inhibitory effect of pancreatic elastase on increased albuminuria in diabetic patients. PMID- 7988348 TI - Increased insulin responsiveness after CS-045 treatment in diabetes associated with Werner's syndrome. AB - Werner's syndrome is a rare inheritated disorder characterized by accelerated aging and is often accompanied by diabetes mellitus or impaired glucose tolerance. Previous reports suggest that insulin resistance is involved in the development of diabetes associated with Werner's syndrome. In the present study, CS-045((+/-)-5-[4-(6-Hydroxy-2,5,7,8-tetramethylchroman-2-ylmet hoxy)benzyl] - 2,4-thiazolidinedione, a new oral hypoglycemic agent which reportedly reduces insulin resistance, was administered to 2 Werner's syndrome patients. The patients were hospitalized for the duration of the study. During a pretreatment period lasting 8 weeks the patients received a controlled diet, however, their previous treatment was unchanged. Throughout the 4-week treatment period, each subject's blood glucose level was measured 7 times each day (07:30, 10:00, 11:30, 14:00, 17:30, 20:00, 22:00) for 1 week at 8, 4, and 1 week before treatment and at 2 and 4 weeks after treatment. To assess insulin action, the euglycemic glucose clamp technique was performed in these subjects at insulin infusion rates of 20, 120 and 400 mU/kg/min before and after 4 weeks of treatment. After 4 weeks of treatment with CS-045, the mean blood glucose level at each time point measured in this study was markedly lower compared to the corresponding pretreatment level.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7988349 TI - The effect of prostaglandin E1.alpha CD on vibratory threshold determined with the SMV-5 vibrometer in patients with diabetic neuropathy. AB - We studied the effect of prostaglandin E1.alpha CD (PGE1) on diabetic peripheral neuropathy by evaluating subjective symptoms and vibration sensation using a new vibrometer (SMV-5). Patients with diabetic neuropathy (n = 38) were divided into three groups; group A received no drugs (control), group B was treated with 1500 micrograms/day of oral methyl vitamin B12 (VB12) for four weeks, and group C received 1.2 micrograms/kg/day PGE1 intravenously for four weeks. There was a close relationship between symptom scores and vibratory threshold (VT). The effect of PGE1 on subjective symptoms and VT were compared with those in groups A and B. Patients who received PGE1 showed a significant improvement rate in pain and hypesthesia compared to patients in groups A and B, and in numbness compared to group A. During the study period, there was no significant change in VT in groups A and B, whereas VT was significantly improved at styloid process (P < 0.05) and at medial malleolus (P < 0.001) in group C. Our results confirmed that PGE1 significantly improved both subjective symptoms and VT, indicating that PGE1 therapy may be useful in diabetic neuropathy. PMID- 7988350 TI - Dropout of young non-insulin-dependent diabetics from diabetic care. AB - We investigated the follow-up status and prognosis of 109 patients with non insulin-dependent diabetes mellitus aged from 10 to 19 years old (66 males and 43 females). Patients who had not attended hospital for at least 20 months up to the end of September 1990 were regarded as defaulters, and were surveyed by questionnaire. There were 62 defaulters (56.9%) among the 109 patients originally enrolled in diabetes care. The defaulters had a significantly higher body mass index (both males and females), mean arterial blood pressure, and fasting blood glucose level than the patients still attending the diabetes clinic, as well as a significantly worse lipid profile. The main reason given for non-attendance was a busy schedule. Compared with patients attending the diabetes clinic, a lower percentage of the defaulters remained on a diet or took regular exercise. Rapid eating was more common among the defaulters than the attendees (92.9% vs. 60%, P = n.s.). Thus, the lifestyle of the defaulters seemed to be undesirable for young diabetic patients. These findings emphasize the importance of effective education and follow-up for young obese patients with non-insulin-dependent diabetes mellitus. PMID- 7988351 TI - Final height attainment in girls and boys with insulin-dependent diabetes mellitus. AB - We compared final height to height at diagnosis (expressed as a standard deviation score, SDS), predicted adult height (according to the Bayley and Pinneau method) and target genetic height (expressed as mean parental height in cm, +6.5 for males and -6.5 for females) in 37 patients (15 males, 22 females) with insulin-dependent diabetes mellitus (IDDM), aged 20.6 +/- 3.3 years (16.6 27), with 11.8 +/- 3.7 years (5.2-19.2) mean duration of disease. In the 22 females, final height (162.4 +/- 5.7 cm; range, 150-174 cm) was higher than predicted (161.5 +/- 7.8 cm; range, 146-176.2 cm) and target genetic height (159.7 +/- 3.8 cm; range, 152.8-167.3 cm), although not significantly. Female patients showed a positive correlation between final height and both predicted (P < 0.05) and target genetic height (P < 0.005). No difference was observed in final height between patients diagnosed in the prepubertal or pubertal phase (162.2 +/- 4.6 cm vs. 163.4 +/- 6.2 cm; P-value n.s.). In the 15 males, final height (173.4 +/- 4.4 cm; range, 166.5-181 cm), lower than predicted (175.4 +/- 4.9 cm; range, 166-183 cm), was higher than target genetic height (169.9 +/- 4.8 cm; range, 162.4-177 cm) (P < 0.05). Male patients showed a positive correlation between final height and target genetic height (P < 0.05). No difference was found in final height between patients diagnosed in the prepubertal or pubertal phase (173.6 +/- 3.5 cm vs. 172.7 +/- 5.5 cm; P-value n.s.).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7988352 TI - Lack of antibodies to glutamic acid decarboxylase in young adults of the high diabetes prevalence Wanigela people of Papua New Guinea. AB - Antibodies to glutamic acid decarboxylase (anti-GAD) are common in typical insulin-dependent diabetes mellitus, and also identify a sub-group of older persons who are originally misdiagnosed as having non-insulin-dependent disease (NIDDM). The Wanigela people of Papua New Guinea are highly susceptible to diabetes mellitus, with a prevalence of 20.4% in urbanised young adults aged 25 34 years. On the basis of clinical features including the presence of obesity and relatively high insulin concentrations the Wanigelas have NIDDM. To determine whether anti-GAD is present in this high prevalence form of diabetes, and to investigate whether there might be an autoimmune component to the disease, we measured anti-GAD in 93 newly-diagnosed diabetic subjects aged 25-44 years, and in 40 controls with normal glucose tolerance. There was no difference in mean levels of anti-GAD in diabetic subjects and normal controls. Two subjects had borderline elevated anti-GAD levels: one was a normal control, and the other a diabetic. This study shows that anti-GAD is not present in this (and probably other) high prevalence variant of NIDDM. Moreover, the results suggest strongly that diabetes in the Wanigela people is unlikely to have an autoimmune component to its pathogenesis. PMID- 7988353 TI - Casualties in Acapulco: results of a study on alcohol use and emergency room care. AB - This article reports the results of an emergency room study carried out in 1987 in three hospitals in Acapulco, Mexico. All patients were interviewed and breath tested for alcohol consumption. The data were analyzed using the case-control methodology. Cases were falls, motor vehicle accidents, fights and assaults, and home accidents. The control group included patients for whom accidents are less frequently reported as alcohol related, i.e., those reporting work place accidents, animal bites and recreational accidents. For positive breathalyzer readings (> or = 10 mg/100 ml of blood alcohol), the odds ration and 95% confidence intervals were statistically significant for falls, 3.45 (1.23-9.66); motor vehicle accidents, 3.85 (1.21-12.01); and fights and assaults, 5.23 (2.36 12.95). The association was non-significant for home accidents, 0.78 (0.20-2.98). Possible biases of this approach are discussed and recommendations are made for selecting better controls for future emergency room studies. PMID- 7988355 TI - A single injection of either flupenthixol decanoate or haloperidol decanoate produces long-term changes in cocaine self-administration in rats. AB - The effect of decanoate forms of flupenthixol and haloperidol on cocaine self administration was evaluated. Forty-two male Wistar rats were implanted with chronically indwelling jugular cannulae and trained to self-administer cocaine (0.6 mg/inj) either on a fixed ratio (FR) 1 schedule or a progressive ratio (PR) schedule. After a stable response pattern was established, animals received a single i.m. injection of either flupenthixol (2.0 mg), haloperidol (2.5 mg) or vehicle (0.1 ml oil). Both neuroleptics produced a long lasting increase in cocaine intake on a FR 1 schedule which reached a peak on post-injection day three and diminished slowly over the next seven days. All animals maintained on a PR schedule showed a long lasting decline in breaking points. These data suggest that the decanoate forms of flupenthixol and haloperidol may attenuate the reinforcing effects of cocaine and indicate that the therapeutic value of depot neuroleptics as anti-cocaine treatments would depend on the economics of cocaine availability. PMID- 7988354 TI - Should tolerance and withdrawal be required for substance dependence disorders? AB - Despite the historical importance of tolerance and withdrawal in the substance abuse nomenclature, empirical evaluations of tolerance and withdrawal relative to other, non-physical, dependence criteria have been infrequent. Based on data from 521 subjects from a newly completed survey evaluating proposed options for DSM-IV substance use disorders, we found, first, across classes of drugs, requiring tolerance or withdrawal had little effect on rates of dependence, as most subjects who met dependence criteria for each drug class also reported tolerance. Second, tolerance and withdrawal did not emerge as superior to the other dependence criteria on several indicators of concurrent and predictive validity, including severity. PMID- 7988356 TI - Cannabinoid receptors in developing rats: detection of mRNA and receptor binding. AB - Despite a large body of research directed at assessing the effects of perinatal cannabinoid exposure, little is known about the development of the cannabinoid receptor. Recent advances, including the cloning of the cannabinoid receptor, have afforded us the opportunity to plot the postnatal ontogeny of the cannabinoid receptor and its mRNA in whole brain using the methods of receptor binding and RNA blot hybridization, respectively. Our results indicate that cannabinoid receptor mRNA is present at adult levels as early as postnatal day 3. The Bmax, on the other hand, increases almost fifty percent with increasing postnatal age, while the affinity does not change. The Hill coefficients for all ages studied were approximately 1. These findings suggest the possibility of a developmental progression for cannabinoid receptor development with receptor mRNA appearing first, followed by a period of rapid proliferation of the receptors themselves. PMID- 7988357 TI - Reporting of HIV risk behaviors by injection drug using heterosexual couples in methadone maintenance. AB - This study sought to identify differences within injection drug using (IDU) couples in reporting of sexual and needle risk behavior. Subjects were thirty nine heterosexual couples entering methadone maintenance. In 33.3% of couples, one member reported sharing needles while the other member reported no sharing. In 12.9% of couples, one member reported sharing injection equipment, while the other member reported no sharing. Agreement was 77.4% between members of monogamous couples regarding frequency of condom use, 80.7% regarding vaginal intercourse with condoms, and 25.8% regarding vaginal intercourse without condoms. Within couples, a number of differences between members of the couple in injection equipment sharing were noted, suggesting that individuals who attempt to protect themselves by not sharing injection equipment may be placed at risk by their sexual partners. Further clinical and research efforts should be directed toward reducing barriers to behavior that would protect both partners. Implications for self-report measurement of HIV risk behavior and for preventive interventions are discussed. PMID- 7988358 TI - Low power? Use two-dimensional confidence regions as a graphical method for depicting uncertainty. AB - Prospective studies of rare outcomes, such as HIV seroconversion or obsessive compulsive disorder, can often result in small sample sizes with limited power for detecting associations. For this reason, it is useful to develop graphical procedures that enable researchers to depict uncertainty around parameter estimates and examine the direction of association when statistical power is low. Classical procedures include the reporting of confidence intervals, which typically are derived from asymptotic normality of parameters estimated using large samples. In this paper, we present a likelihood-based procedure for the estimation of the confidence region of two parameters from a conditional logistic regression of a nested case-control study with a relatively small number of cases. Graphical depiction of the confidence regions provides an easily comprehensible procedure to quantify the uncertainty of the estimation based on small samples. PMID- 7988359 TI - Influence of ethanol on gastric absorption and metabolism of albendazole and mebendazole. AB - The effect of ethanol administration on gastric absorption in rats of two benzimidazole derivatives has been studied. The ethanol administration was carried out as both acute (5%, 10% and 15% w/v of ethanol in the perfusion solution), and chronic (15, 30 and 120 days) forms. Two benzimidazole derivatives were used: albendazole (ABZ) and mebendazole (MBZ). The administration of ethanol did not affect the kinetic mechanism of the absorption process (simple diffusion) but the absorption rate decreased in all treatments except in 5% acute ethanol, presumably due to the improved solubility of the drugs. Plasma, bile and liver levels after gastric perfusion suggest a possible interference of ethanol metabolism with drug hepatic metabolism. PMID- 7988360 TI - Are men or women more likely to stop drinking because of alcohol problems? AB - Using a national population sample of adults who had ever consumed at least 12 drinks per year, men and women were compared in terms of the proportions who had stopped drinking because of alcohol problems. Overall, 24% of the male drinkers and 31% of the female drinkers had stopped drinking as of the time of interview, but men were more likely than women to have stopped drinking because of alcohol related problems (4.3 vs. 2.3%). After using survival techniques to adjust for women's greater competing risk of stopping drinking for other reasons and men's greater exposure time due to their earlier initiation of drinking, the conditional probabilities of having stopped drinking because of alcohol problems were almost identical for men and women during the first 15 years of their drinking histories. Thereafter, the conditional probabilities were about 50% higher for men than for women. The observed durations of drinking history were about five years longer for men than women. After controlling for sociodemographic characteristics, family history of alcoholism, and patterns of alcohol consumption, there was no gender difference in the hazard of stopping drinking because of alcohol problems among persons who drank alcohol on less than a daily basis during their period of heaviest consumption. However, among daily drinkers, the hazard of stopping drinking because of alcohol problems was greater for women than men, by a factor of 1.5 to 3, depending on quantity of consumption and interval since first drink. PMID- 7988361 TI - The effect of chronic naltrexone pretreatment on associative vs. non-associative morphine tolerance. AB - The purpose of this study was to examine the effect of chronic naltrexone on associative and non-associative morphine tolerance. Rats were given nine injections of either naltrexone (5 mg/kg) or saline during a 5 day period. Following this pretreatment, all rats received 6 morphine injections (5 mg/kg) during the next 14 days. For half the rats in each pretreatment condition, morphine was injected in a distinctive room (paired) while the other half received morphine in the home cage (unpaired). All rats were given the seventh morphine injection (5 mg/kg) in the distinctive room and tested for analgesia. Context-specific tolerance was found in both pretreatment conditions. Compared to pretreatment with saline, naltrexone pretreatment produced more analgesia in the unpaired condition but had no effect in the paired condition. These results suggest that antagonist pretreatment attenuated tolerance that was not mediated by explicit environmental cues but had no effect on context-specific analgesic tolerance. PMID- 7988362 TI - Plasma methadone monitoring with methadone maintenance treatment. PMID- 7988363 TI - Alcohol pretreatment alters the metabolic pattern and accelerates cocaine metabolism in pigs. AB - We investigated whether alcohol pretreatment would affect the disposition and metabolic pattern of intravenously (i.v.) administered cocaine in pigs. Six pigs (Group A) received alcohol (1 g/kg/day) and six pigs (control; Group D) received an equal volume of isocaloric dextrose 44% in water for 10 days via an intragastric tube. On day 11, arterial samples were taken for five hours following an intravenous administration of cocaine hydrochloride (4 mg/kg). Plasma concentrations of cocaine and its major metabolites were analyzed by HPLC method. Significant decrease in plasma half-life (10 +/- 1.2 vs. 18.7 +/- 1.4 min), and significant increases in apparent volume of distribution (73 +/- 6 vs. 51 +/- 31) and clearance (5.37 +/- 0.6 vs. 1.82 +/- 0.1 l/min) were seen in alcohol pretreated pigs as compared with control pigs (P < 0.05). Significant increases in plasma concentrations of benzoylecgonine (P < 0.05), and insignificant differences in ecgonine methyl ester and norcocaine levels were seen between the two groups. Neither ecgonine nor cocaethylene was detected in the blood samples. Our data show that alcohol administration for ten days accelerated the elimination of i.v. administered cocaine and altered its metabolic pattern in pigs. PMID- 7988365 TI - [Endoscopic diagnosis of colonic tuberculosis]. AB - A 67-year-old woman had developed weakness, fatigue and a 10 kg weight loss over the past year. On examination a cylindrical mass was palpated in the right middle abdominal cavity. Erythrocyte sedimentation rate was increased to 87/126 mm, there was an hypochromic anaemia (haemoglobin 9.1 mg/dl) and an hypoalbuminaemia (32 g/l) with an increase in alpha 2-globulins (9.4 g/l), Cholinesterase activity was decreased to 588 U/l. X-ray film of the abdomen revealed a calcified mesenteric lymph-node and coloscopy demonstrated polypoid tumorous changes with ulcerations, extending from the pole of the caecum to the right flexure. Histological examination showed epithelioid-cell granulomas with Langhans giant cells. Culture grew Mycobacterium tuberculosis, confirming the diagnosis of intestinal tuberculosis. She was treated with oral doses of isoniazid (300 mg daily), rifampicin (600 mg daily) and pyrazinamide (2 g daily) for 2 months, followed by isoniazid and rifampicin for a further 4 months. After this the laboratory tests were within normal limits and urine as well as stool samples contained no acid-fast bacilli. As the patient felt so well she declined another coloscopy. PMID- 7988364 TI - [The effect of a low-dose hydrochlorothiazide therapy on the bone mineral content of the axial and peripheral skeleton]. AB - An increase in bone mineral content (BMC) as well as a decrease in the incidence of fracture of the proximal femur have been described in patients on thiazide diuretic treatment. A study was undertaken to assess, by means of dual X-ray absorptiometry, the effect of chronic low-dosage antihypertensive treatment with hydrochlorothiazide (HCT; < or = 25 mg daily) on lumbar vertebrae (representing the axial skeleton) and the nondominant radius (peripheral skeleton). Measurements were made on 27 women (mean age 63.8 +/- 8.2 years) and 23 men (65.9 +/- 9.5 years) and compared with a control group of 19 women (62 +/- 8.7 years) and 20 men (65.9 +/- 9.5 years) with minor surgical or dermatological lesions who had never taken HCT or other drugs with potential effects on mineral bone metabolism. In men who had been on HCT for more than 5 years, BMC of the lumbar vertebrae was higher by 10.3% and of the radius by 3.8% than among the controls (differences not significant). In women who had been on HCT for more than 5 years, the corresponding increases were 19.6% (P < 0.05) and 5.4% (not significant). Among those patients who had been on HCT for less than 5 years there were no significant differences compared with the control group. There were no significant differences between the groups relating as regards the proximal radius which, in contrast to the ultradistal radius, consists predominantly of cortical bone. -These data indicate that, while HCT has only a slight influence on BMC, it can be considered to have a desirable associated effect in the antihypertensive treatment of elderly patients. PMID- 7988366 TI - [Treatment of an intermittent stomach volvulus using gastropexy via percutaneous endoscopic gastrostomy]. AB - A 72-year-old woman had been experiencing upper abdominal pain and vomiting for 2 years. On physical examination the abdomen was swollen and pressure sensitive. She had a leukocytosis (11,400/microliter) and hypokalaemia (3.6 mmol/l). X-ray films of the chest and abdomen revealed a large gastric air-bubble with two fluid levels of different height and an elevated left diaphragm, findings which suggested gastric volvulus. Most of the fluid was evacuated via a nasogastric tube. The stomach interior was difficult to examine by gastroscopy: it was only after withdrawal of the gastroscope from the duodenum that a normal gastric architecture was demonstrated, the volvulus apparently having been reduced during the gastroscopy. The gastric mucosa showed ulcerations and erosions. Gastropexy by gluing together the peritoneal layers was undertaken via dual percutaneous endoscopic gastrostomy. The catheters were removed after 4 weeks when the ulcerations had healed. The patient has been free of symptoms for more than a year so far. PMID- 7988367 TI - [Adjuvant therapy in colorectal carcinomas]. PMID- 7988368 TI - [Therapeutic drugs. Magnesium]. PMID- 7988369 TI - [Problems of equivalency points during therapy with glucocorticoids. A comparison of the clinical pharmacokinetics and pharmacodynamics of prednisolone and methylprednisolone]. PMID- 7988370 TI - [Hypocholesterolemia]. PMID- 7988371 TI - [Psychosocial problems during long-term immunosuppression after organ transplantation]. PMID- 7988372 TI - [Resistance against activated protein C. Most frequent disorder in venous thromboses?]. PMID- 7988373 TI - [Pacemaker therapy for the sick sinus node syndrome. Does the atrially involved pacemaker system lower the frequency of atrial fibrillation and thromboembolic complications as well as mortality?]. AB - Between 1986 and 1992, pacemakers were implanted in 307 patients with symptoms caused by the sick sinus syndrome (SSS). 301 patients were regularly followed up (161 men, 146 women, mean age 72.9 [27-91] years) of whom 180 had a VVI, 65 and AAI and 58 a DDD/DDI pacemaker. Mean follow-up period was 58.3 months for VVI stimulated patients and 35.6 months for atrial paced patients. The data were analysed retrospectively to ascertain whether a change in pacemaker treatment to a more physiological system produced any lowering in the mortality rate, incidence of permanent atrial fibrillation (AF), and thromboembolic phenomena. The annual mortality rate of the VVI-stimulated patients was 6.9%, that of atrial paced patients 2.8%. Age, abnormal ventricular function, survived resuscitation and diabetes mellitus each correlated with a shortened life expectancy already at the time of implantation, regardless of the pacemaker mode. Permanent AF was more frequent during VVI stimulation (16% vs 7%), especially if it had been preceded by intermittent AF (26% vs 13%). But there was no significant difference with regard to transitory cerebral ischaemic episodes and peripheral arterial emboli (15% vs 10%). Fewer patients with atrial pacing went into heart failure (20% vs 30%). Four patients developed a high-grade atrioventricular (a-v) block on AAI stimulation (annual incidence 2.4%). - These observations suggest that patients with SSS should always have atrial paced pacemaker systems. If a-v conduction is disturbed, a bifocal pacemaker is the system of choice. PMID- 7988374 TI - [Polyneuritis and myositis in Trypanosoma gambiense infection]. AB - During a four-week trip to Nigeria a 54-year-old German developed a fever of 39 degrees C. Later on he had lymphadenopathy, pretibial oedema, dyspnoea and weight loss. After 16 weeks a wreath-like pale pink skin rash, increased pulse rate with pulse deficit and hepatosplenomegaly were noted. Abnormal laboratory findings were an increased blood sedimentation rate (95 mm), raised immunoglobulin M (483 mg/dl), haemoglobin of 12.0 g/dl, mean corpuscular volume of 76 fl and Borrelia IgM antibody titre of 1:512. The electrocardiogram was suggestive of myocarditis: the cardiac symptoms were controlled with digoxin and verapamil. The patient's general condition deteriorated while he was receiving antibiotic treatment with tetracycline and penicillin. Cerebrospinal fluid (CSF) showed an increased cell count (39/microliters) and albumin (0.98 g/dl). There was a mild, predominantly proximal, tetraplegia which--on the basis of electromyographic and biopsy findings--was thought to be due to polyneuritis and myositis. At this stage blood smear and CSF examination revealed Trypanosoma. He thereupon received suramin (1.0 g) and prednisolone (120 mg down to 40 mg) daily, to which melarsoprol was added after 6 days (0.5 ml up to 5.0 ml daily for 36 days). Almost all symptoms then regressed within 6 weeks. PMID- 7988376 TI - [Diagnosis and therapy of anal carcinoma]. PMID- 7988375 TI - [Generalized IgG-lambda plasmocytoma and stenosis of a Cimino shunt caused by plasma cell infiltration]. AB - A 56-year-old apparently healthy man was on routine examination found to have a paraproteinaemia, classified as an IgG-lambda plasmocytoma in stage 1 on the basis of a raised IgG level (1950 mg/dl) and partly binuclear plasma cells in bone marrow. When 5 months later the IgG concentration had increased to 2980 mg/dl and the proportion of plasma cells in bone marrow to 15%, treatment was begun with melphalan (0.25 mg/kg) and prednisolone (2 mg/kg), both on 4 successive days every 6 weeks. The patient's general condition rapidly worsened after 6 months. The extent of osteolysis increased, necessitating radiotherapy of the vertebrae as well as a change in treatment to vincristine, cyclophosphamide, doxorubicin and prednisolone. At that time renal failure set in. But the prophylactically placed Cimino shunt had become infiltrated with plasma cells causing shunt stenosis and soft-tissue swelling. The infiltration was reduced by irradiation with 18 Gy. Numerous bluish skin discolorations now appeared and plasma cell infiltrates were shown in lung and pleura, as well as in the abdomen. The patient died 15 months after the diagnosis had been made. PMID- 7988377 TI - [The role of endothelin in the cyclosporine side effects of nephrotoxicity and arterial hypertension]. PMID- 7988378 TI - [Complaints against the national health insurance physicians' association regarding unauthorized medical writing]. PMID- 7988379 TI - [Indications for plague vaccination and chemoprophylaxis]. PMID- 7988380 TI - [A beta-receptor blocker as an emergency precaution in acute myocardial infarction?]. PMID- 7988381 TI - [Pulmonary aspergillosis]. PMID- 7988382 TI - [Pulmonary aspergillosis]. PMID- 7988384 TI - Immunotoxicity of 180 day exposure to polydimethylsiloxane (silicone) fluid, gel and elastomer and polyurethane disks in female B6C3F1 mice. AB - Millions of people have been exposed to silicones which are present in consumer goods such as cosmetics and toiletries, processed foods and household products. In addition, silicones have been used extensively in medical practice as a lubricant in tubing and syringes, and as implantable devices. A silicone widely used in medical practice is polydimethylsiloxane. This study was undertaken to determine the immunotoxicologic potential of long term exposure to the principal constituents of breast implants: silicone fluid, silicone gel and silicone elastomer. An alternative covering for devices containing silicone gels, polyurethane, was also included in the study. Silicone fluid and gel were injected subcutaneously into female B6C3F1 mice (1 ml/mouse) and 6 mm disks of silicone elastomer or polyurethane were implanted subcutaneously. There were no treatment-related deaths or overt signs of toxicity during the 180 day exposure. None of the tested materials had notable effects on body or organ weights, erythrocytes or leukocytes in the blood, blood chemistries such as alanine aminotransferase, urea nitrogen, glucose, albumin or total protein, or serum CH 50 or C3 levels. The cellularity of the bone marrow and responses to CSF-GM and CSF-M were normal. The tested silicones and polyurethane marginally reduced the level of Ig+ cells in the spleen but did not consistently alter the distribution of T cell surface markers. The antibody response to sheep erythrocytes was not markedly altered, nor were proliferative responses to concanavalin A, phytohemagglutinin, lipopolysaccharide or allogeneic cells. Reticuloendothelial function was normal, as was phagocytosis of chicken erythrocytes and Covaspheres by adherent peritoneal cells. Natural killer cell activity was depressed in all silicone treatment groups and in mice implanted with polyurethane. No silicone or polyurethane treatment group displayed altered susceptibility to a challenge with Listeria monocytogenes, Streptococcus pneumoniae or the B16F10 tumor. The only consistent effect of 180 day exposure to silicone materials or polyurethane was a modest depression of natural killer cell activity. PMID- 7988383 TI - Subchronic 10 day immunotoxicity of polydimethylsiloxane (silicone) fluid, gel and elastomer and polyurethane disks in female B6C3F1 mice. AB - Millions of people have been exposed to silicones because of the widespread use in consumer products such as cosmetics and toiletries, food products, household products and paints. Silicones have wide use in medical practice, including lubricants in tubing and syringes, and as implantable devices. The most prevalent silicone in medical use is polydimethylsiloxane. This study was undertaken to determine the subchronic immunotoxicologic potential of the principal constituents of breast implants: silicone fluid, silicone gel and silicone elastomer. An alternative covering for devices containing silicone gels, polyurethane, was also included in the study. Silicone fluid and gel were injected subcutaneously into female B6C3F1 mice (1 ml/mouse) and 6 mm disks of silicone elastomer or polyurethane were implanted subcutaneously. There were no treatment-related deaths or overt signs of toxicity. None of the tested materials had notable effects on body or organ weights, erythrocytes or leukocytes in the blood, blood chemistries such as alanine aminotransferase, urea nitrogen, glucose, albumin or total protein. The cellularity of the bone marrow and responses to CSF-GM and CSF-M were normal. The tested silicones did not alter the distribution of B cells and T cells in the spleen, but polyurethane perturbed the distribution of CD4+CD8+ and CD4-CD8- T cells. The antibody response to sheep erythrocytes was not markedly altered, nor were proliferative responses to concanavalin A, phytohemagglutinin, lipopolysaccharide or allogeneic cells. Reticuloendothelial function was normal, but polyurethane evoked an enhanced phagocytosis of Covaspheres by adherent peritoneal cells. Natural killer cell activity and serum complement were not altered. All silicone materials afforded modest protection to a challenge with Listeria monocytogenes that killed 40 to 58% of control mice. Host resistance to Streptococcus pneumoniae or the B16F10 tumor was not affected by any of the treatments. There is a pattern indicative of some perturbation of T cell differentiation in mice implanted with a polyurethane disk. PMID- 7988385 TI - Immunotoxicity of nitrobenzene in female B6C3F1 mice. AB - Nitrobenzene (NBZ) is primarily employed as an oxidizing agent in the synthesis of analine and benzene compounds. It produces myelotoxic effects and effects on erythrocytes in both animal models and man. Reported hepatosplenomegaly and effects on the bone marrow are indicators that NBZ may be immunotoxic. In these studies, female B6C3F1 mice were exposed to 30, 100 and 300 mg/kg of NBZ in corn oil by gavage for 14 consecutive days. To assess the immunotoxic potential of NBZ, body and organ weights were determined and selected immunologic and host resistance responses were studied. In these studies, the liver and spleen appeared to be the primary target organs. Both liver and spleen weights were dose dependently increased. Gross histopathologic examinations revealed significant changes in the spleen, consisting of severe congestion of the red pulp areas with erythrocytes and reticulocytes. Serum chemistry profiles showed increases in alanine aminotransferase and aspartate aminotransferase activities, indicating liver toxicity. Hematologic studies showed a decrease in erythrocyte number and a concomitant increase in mean corpuscular hemoglobin and mean corpuscular volume. A dose-dependent increase in peripheral reticulocytes was also seen. DNA synthesis was enhanced, as was the number of formed elements and the number of monocyte/granulocyte stem cells in the bone marrow of treated mice. IgM responses were decreased and the phagocytic activity of macrophages in the liver was dose dependently increased with a concomitant decrease in the activities in the spleen and lung. Other immunological parameters examined were unchanged. Host resistance to microbial or viral infection was not markedly altered by NBZ; however, there were trends towards increased susceptibility where T-cell function contributes to host defense. These data indicate that NBZ-induced hemolysis and liver injury are linked to the observed alterations in bone marrow activity. PMID- 7988386 TI - Immunotoxicity of mono-nitrotoluenes in female B6C3F1 mice: I. Para-nitrotoluene. AB - para-Nitrotoluene (p-nitrotoluene) is used primarily as an intermediate in the production of various dyes, explosives, pharmaceuticals, and in the production of rubber and agricultural products. Previous investigations indicated that p nitrotoluene was mutagenic in the Ames Test and that other mono-substituted nitrotoluenes bound covalently to hepatic macromolecules. The objective of these studies was to evaluate the potential immunotoxicity of p-nitrotoluene in mice exposed by the oral route. Mice exposed to p-nitrotoluene (200-600 mg/kg) daily for 14 days showed modest dose-dependent increases in liver and spleen weights. The livers of mice exposed subchronically to 400 and 600 mg/kg showed a mild to moderate swelling of the hepatocytes adjacent to the central veins; this swelling appeared to be reversible and there was no evidence of necrosis. The proportion of monocytes in blood was decreased in mice treated with p-nitrotoluene or toluene. Serum chemistries, bone marrow cellularity and the number of CFU-M and CFU-GM were unaffected. Immunologic investigations showed p-nitrotoluene suppressed the IgM response to sRBC and the DHR response to KLH. There was a 24% decrease in the percentage of CD4+ T lymphocytes in the spleen. There was no dose dependent alteration of peritoneal macrophage numbers or differential count, unstimulated natural killer cell activity, response to B cell mitogen LPS, C3 activity or interferon levels. Exposure of mice to p-nitrotoluene decreased resistance to Listeria monocytogenes but not to Streptococcus pneumoniae, Plasmodium yoelii or the B16F10 melanoma, and increased resistance to the PYB6 tumor. These studies indicated that the immune system is an important target for toxicity of p-nitrotoluene. The decreased host resistance to L. monocytogenes can be attributed to the decrease in T lymphocytes and to a decreased delayed hypersensitivity response to KLH. PMID- 7988387 TI - Immunotoxicity of mono-nitrotoluenes in female B6C3F1 mice: II. Meta nitrotoluene. AB - The nitrotoluenes are chemicals used in dyes, agricultural products, pharmaceuticals and explosives. In the present studies, the toxicology and immunotoxicity of meta-nitrotoluene (m-nitrotoluene) were evaluated. Mice, exposed to m-nitrotoluene at dose levels of 200, 400 and 600 mg/kg/body weight for 2 weeks by gastric gavage, gained body weight over the treatment period to a slightly greater extent than the control groups. Of the selected organs weighed, the liver and kidney of mice exposed to m-nitrotoluene were increased in weight while the thymus weight was decreased. The liver of mice exposed to m nitrotoluene, but not ortho-nitrotoluene, showed slight to moderate swelling of the hepatocytes adjacent to the central veins. The hepatocyte swelling appeared to be reversible and there was no evidence of necrosis. The hematology and serum chemistries examined were unaffected by m-nitrotoluene exposure although there were modest decreases in the percentage of polymorphonuclear leukocytes and eosinophils in differential blood counts. Bone marrow cellularity and the number of CFU/M and CFU/GM were unaffected by m-nitrotoluene exposure. m-Nitrotoluene suppressed the IgM response to sRBC and the DHR response to KLH. There was a slight (8%) decrease in the percentage of B lymphocytes in the spleen. The response to the T cell mitogens was suppressed by as much as 39%. Fc-mediated adherence and phagocytosis of chicken erythrocytes and NK cell activity were increased dose dependently in mice exposed to m-nitrotoluene. Several immune parameters were unaffected by exposure to m-nitrotoluene, including the IgG response to sRBC, responses to the B cell mitogen LPS and to allogeneic cells, and serum interferon levels. Resistance to Streptococcus pneumoniae and Plasmodium yoelii were unaffected also. Resistance to the tumor model PYB6 was increased. Exposure of mice to m-nitrotoluene decreased resistance to Listeria monocytogenes. The decreased resistance to L. monocytogenes may be related to an effect on T cells, evidenced by a decrease in T cell numbers and in the DHR. PMID- 7988389 TI - Attic cholesteatoma. PMID- 7988390 TI - Beginner's guide to primary inhalant allergens. Part 6: Gymnosperm (coniferous) trees. PMID- 7988388 TI - Immunotoxicity of 2,4-diaminotoluene in female B6C3F1 mice. AB - 2,4-Diaminotoluene (DAT) has been demonstrated to be a potent carcinogen. The present studies were carried out to determine the toxic and immunotoxic potential of DAT. Mice exposed to DAT at 25-100 mg/kg per day for 14 days by gavage showed a 42% increase in liver weight and a slight decrease in spleen weight. Histopathologic evaluation of selected organs showed the liver to be the major target with morphological changes which were dose dependent. The high dose (100 mg/kg) was associated with moderate centrilobular necrosis. No abnormal structure was noted in the spleen, lungs, thymus, kidney or mesenteric lymph nodes. The liver toxicity was associated with an elevation in alanine aminotransferase activity. The only change noted in selected hematologic parameters was a 64% increase in peripheral blood leukocytes. Mice exposed to DAT showed a decreased IgM and IgG response to sheep erythrocytes. The decrease was not a function of a decreased number of B cells because the number of B cells increased dose dependently. Proliferative capacity of immunocompetent cells was not impaired by exposure to DAT as measured by the response to several mitogens. The delayed hypersensitivity response to keyhole limpet hemocyanin in mice exposed to DAT was increased. Natural killer cell activity was decreased dose dependently and may represent a spleen cell pool shift because the number of B cells increased in the presence of a decreasing spleen size. Serum C3 was suppressed at the high dose of DAT. Phagocytosis by splenic macrophages, but not peritoneal macrophages, was inhibited by DAT exposure. DAT exposure for 14 days decreased host resistance to the bacteria, Streptococcus pneumoniae and Listeria monocytogenes, while host resistance to the pulmonary tumor model, B16F10, and the PYB6 fibrosarcoma was unaffected by DAT exposure. These data indicate that DAT is hepatotoxic and perturbs the differentiation and maturation of leukocytes. PMID- 7988391 TI - Acute mucosal tear and vocal fold hemorrhage. PMID- 7988392 TI - Endoscopic anatomy of the anterior ethmoidal artery. PMID- 7988393 TI - Literature review: the common cold. AB - Most colds are caused by rhinovirus infection, perhaps facilitated by chilling or stress. Virus infection begins in the nasopharynx and causes spotty destruction of the nasal ciliated epithelium. Transmission occurs chiefly via droplets of various sizes transported through the air, but some types of virus persist in moist secretions on handled objects and may retain their infectiousness. Living in crowded, poorly-ventilated quarters facilitates transmission. Not many virus particles survive in saliva and it is difficult to infect via the lips or mouth. Kissing does not efficiently spread cold infection. Prophylactic treatment with interferon does not protect against cold infection. Aspirin and acetaminophen reduced serum antibody response and increased nasal symptoms in a controlled Australian study. The combination of intranasal interferon and ipratropium with oral naproxen gave promising results in experimental rhinovirus inoculation. Basically, there has been little or no progress towards effective cold treatment in the past century. PMID- 7988394 TI - Acute mastoiditis--revisited. AB - The clinical course and causative organisms were studied in 18 patients with acute mastoiditis, 13 of whom (72%) had no previous history of middle ear disease. Their age ranged from 5 months to 21 years, and duration of middle ear symptoms immediately prior to admission ranged from 1 to 45 days (average 9.7 days). None had undergone a myringotomy prior to admission, while 13 (72%) had been receiving antibiotic treatment for acute otitis media. Three were admitted with intracranial complications. Bacteria were isolated in 10 of the 16 patients in whom samples were available for bacterial culture, and included Streptococcus pneumonia (2), Streptococcus pyogenes (2), Staphylococcus aureus (2), Staphlococcus coagulase negative (2), Klebsiella pneumonia (1), and Pseudomonas aeruginosa (1). Of the 17 patients treated by us, 11 received surgery. Acute otitis media, secretory otitis media, acute mastoiditis, subacute mastoiditis and masked mastoiditis create a continuum. Antibiotic treatment for acute otitis media cannot be considered as an absolute safeguard against acute mastoiditis. When antibiotics are prescribed for acute mastoiditis before culture result is available, an anti-staphylococcal agent should be included. At least some patients with acute mastoiditis develop a primary infection of the bony framework of the middle ear cleft. The prevalence of the intracranial complications in acute mastoiditis is still high and may appear soon after or concomitant with the first sign of acute mastioditis. PMID- 7988396 TI - Cochlear implantation and variation of facial nerve anatomy: a case report. AB - Cochlear implantation becomes more common with every passing year. Since adequate exposure of the round window requires a facial recess approach, facial nerve variation and anomalies could potentially alter the surgical approach significantly. We report the case of a patient with a variation of facial nerve anatomy. The nerve was found to be lateral to the annulus in its mastoid segment and required retrofacial dissection to approach the round window. A good result was achieved in this patient, demonstrating that facial nerve anomalies need not be a barrier to successful implantation. The reported congenital anomalies of the facial nerve are discussed, along with their influence on cochlear implantation. A knowledge of these variations is mandatory for those engaged in implant surgery. PMID- 7988395 TI - The role of total laryngectomy in the management of intraluminal upper airway invasion by well-differentiated thyroid carcinoma. AB - Intraluminal invasion of the upper airway by well differentiated thyroid carcinoma is very uncommon, and the management can be problematic. Many conservative, reconstructive-type surgical procedures have been advocated to maintain normal laryngeal function. Although voice preservation is desirable, it may not always be in the patient's best interest and radical surgery, including total laryngectomy, may be necessary. We describe three cases in which total laryngectomy was performed, and review the indicators for this procedure in the treatment of this difficult to manage condition. PMID- 7988398 TI - Antral rhinolithiasis and tooth filling. AB - Two cases of antral rhinoliths are described. The pathogenesis, clinical features, differential diagnosis and treatment are discussed. PMID- 7988397 TI - The bone-anchored hearing aid: principal design and audiometric results. AB - The principle of the bone-anchored hearing aid (BAHA) is simple: sound vibrations are directly transmitted to the skull bone via a skin-penetrating titanium implant, and then are further transmitted to the cochlea, bypassing the middle ear. The present paper summarized the audiometric results from 122 patients with an average follow-up time of 5.6 years. When herein-suggested indications for treatment with the bone-anchored sound processor HC 300 are followed, the success rate is very high. The improved quality of life reported by the patients is a combination of improved quality of sound (warble tone threshold, speech reception threshold, and discrimination in noise), improved comfort, and relief from middle ear and ear canal disease occasioned by conventional hearing aids. PMID- 7988399 TI - Sinonasal hemangiopericytoma. AB - Sino-nasal hemangiopericytomas are rare indolent mesenchymal tumors which slowly invade local tissue. Electronmicroscopy and immunohistochemical techniques may be necessary to differentiate hemangiopericytomas from other sarcomatous tumors. Differentiation between malignant and benign tumors poses a difficult task, therefore clinical correlation as well histological confirmation is necessary to establish a diagnosis. Due to the low incidence of distant metastasis and low mortality, surgery consisting of wide local excision is usually curative. PMID- 7988400 TI - Carcinoid tumor of the middle ear. AB - Carcinoid tumor of the middle ear is a very rare benign neoplasm, which may be mistaken for a malignant tumor. We present two new cases together with a review of 28 previously reported cases. Nearly all patients had progressive hearing loss, most often of the conductive type. About half of the patients complained of tinnitus and fullness of the ear. The typical otoscopic picture was erythema or lateral bulging of the tympanic membrane, which was intact in most patients. The tumor was most often localized to the middle ear with varying degree of extensions into neighboring areas. It often encapsulated the ossicles, which sometimes were eroded. Systemic symptoms were only reported in two cases. The tumor is clinically benign and total excision of the tumor and affected ossicles is an adequate treatment. The correct diagnosis, which should be considered in case of any adenomatous tumor of the middle ear, requires immunohistochemical and ultrastructural procedures. PMID- 7988401 TI - [Erwin Stransky and intrapsychic ataxy]. AB - The eventful beginnings of the concept of schizophrenia are not widely known in France. Most of the relevant texts are German in origin and French readers have access to very few of them. Yet the concept of schizophrenia has largely been adopted; everything that can contribute to the understanding of its elaboration is of importance. This elaboration did not take the form of a series of brilliant ideas from Kahlbaum, Kraepelin and Bleuler but rather the synthesis by these authors of the theories of their time - theories generally unknown to the French public. One such is the theory of intrapsychical incoordination, propounded by the prolific and interesting Viennese, Erwin Stransky, well known in German speaking countries but not in France. He was, in 1903, the first to emphasize the importance of inaffectivity in dementia praecox. He devised an explanatory model of this disease, indicating its origin as the variable alteration of the relationship between what he termed thymo and noopsyche. Stransky was the first to speak of intrapsychical ataxy, his model offers an explanation for spectacular remissions from dementia praecox and for pseudo-lucidity. Intrapsychical ataxy, according to the model, is of diagnostic value, allowing a distinction to be made between the paralogies and "wordsalads" of hysterics (only thymopsychic) and those of dementia praecox (only noopsychic).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7988402 TI - [Dysthymic schizophrenia. An investigation of its evolution]. AB - Schizo-affective psychosis raises the nosological problem of the boundaries between the schizophrenia and the affective disorders. In the french classification (I.N.S.E.R.M., 1968) there is only the group of "chronic schizophrenia with mood disorders". In the DSM III-R the schizo-affective psychosis has its own criteria for the first time. A brief historical survey reveals the vicissitudes of the evolution of this american concept. J. Kasanin first proposed this term in 1932 to differentiate from the dementia praecox a group of cases with good prognosis. For all that, the schizo-affective psychosis remained included in the schizophrenia illness until the DSMII (1968). Under the influence of factors (principally the international comparative studies of diagnosis of mental disorders) the american psychiatry reconsidered its system of classification and elaborated the Research Diagnosis Criteria (Spitzer, 1975). The first studies quickly led to an opposite position because the schizo affective psychosis became principally a subgroup of the affective disorders (DSM III, 1980). The studies of the last ten years generally criticized this new classification. Among the schizo-affective group they tried to separate the schizophrenic cases from the affective cases by subdivisions according different axes (mainly schizophrenic vs mainly affective, manic type vs depressive type, unipolar type vs bipolar type). Today the review of these studies did not lead to resolve the nosological problem. However the studies corroborate the model that schizo-affective illness is a heterogeneous disorder with schizophrenic cases and affective cases. PMID- 7988404 TI - [Initial contact in clinical interview with patients suffering from chronic insomnia]. AB - One of the most controversial issue concerning chronic insomnia is its association with psychopathology. Many patients tend to present their sleep disturbances as isolated, whereas others admit that they have difficulties in other sectors of their life too. If psychopathology exists in chronic insomnia, it should manifest itself in the form of defensive mechanisms which can be clinically observed. In order to have information concerning this problem, the initial interview of patients with chronic insomnia has been analysed in every details, in order to detect behavioural features and characteristics of verbal expression, indicating that defense mechanisms are working. A group of 100 patients from the specialized consultation for sleep disorders has been studied They were referred by their physicians. The patients with a somatic disease or a psychiatric condition corresponding to a diagnostic on axis I of DSM III-R were not included. The patients with a form of insomnia corresponding to psychophysiological insomnia, idiopathic insomnia or sleep state misperception of the international classification were included in this sample. For all patients except 2 of them, the initial interview was audiovisually recorded. This interview aimed at establishing the clinical features of the disturbance, the psychiatric and somatic condition as well as the history of the trouble and the treatment taken at the time or attempted in the past. After an initial open query: "what seems to be the problem?", a semi-structured interview was conducted to obtain information about nocturnal sleep, daytime condition, dream and parasomnia, the history of the disturbance and the treatment. Anxiety and depression, as well as other psychiatric conditions were systematically investigated. Under these conditions, the patients showed from the very beginning of the interview, noticeable characteristics in their behaviour and verbal expression. Therefore, it is essentially the first 10 minutes of the interview that have been analysed. One exception was regressive weepiness, which usually appeared later in the interview. The audio-visual recording was analysed two times, two months apart, and a number of individual traits have been scored for presence or absence. Only the most obvious traits have been scored. In the behavioural presentation of the patient, detachment, eye avoidance and distant attitude were most commonly observed. Many patients also showed some signs of tension and anxiety. The other traits were smile, immobility of the body posture, incessant movements and tics, bored attitude, mannerism, difficulties to concentrate, retardation or weepiness. The formal characteristics on verbal expression can indicate logorrhea, or in contrast very parcimonious expression, precipitated elocution which makes the patient difficult to understand, or montonous voice. From the point of view of verbal content, the speech is often vague, hesitant, dispersed or superficial, the patient going rapidly from one line to the next one. Some patients have problems to focus on what they want to explain.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 7988403 TI - [Communication disorders in schizophrenic patients. Cognitive explanation and clinical reconsideration]. AB - The definition of schizophrenic patients communication disorders sets many problems (partly linked to the descriptive vagueness of the Bleuler mental dissociation syndrome) and leads today to give up those signals, considered as of little specification, for symptoms of easier definition. Nevertheless, french clinicians go on using the dissociation concept to make the diagnostic of schizophrenia, faithful to Bleuler teaching according to which the communication of these patients would be very specific. The object of this article is to take up with the Bleuler logic and to propose hypothesis of cognitive abnormalities that underlie the symptomatic expression of the communication troubles of these patients and point out, from these hypothesis, how a more specific rereading of the language, thought and communication disorders is possible. Two cognitive abnormalities are suggested by the literature data to explain some schizophrenic communication disorders, abnormalities which seem at least partly independent. The first one can be described in the terms of a model of action and brings down communication to its dimension of discursive action. The authors define it as a trouble of a mechanism of action supervision, of the action monitoring, or of the planning of discourse. The symptomatic expressions of this trouble may be described when the subject is under interview conditions soliciting it Examples of such clinical situations are given. The second abnormality may be described in the terms of the "Theory of Mind" and concern the difficulties of some schizophrenic patients to attribute mental states to their interlocuters. Here again, examples of clinical conditions are given, allowing us to investigate this abnormality. PMID- 7988405 TI - [Schedule for evaluation of the deficit syndrome in schizophrenia: Schedule for Deficit Syndrome (SDS) (Kirkpatrick et al.). Importance pertinence of the SDS. Introduction of the French version]. AB - The negative symptoms of schizophrenia have generated a great interest leading some authors (Crow, Andreasen, Kay) to delineate schizophrenic subtypes based on their presence or absence. Carpenter et al. have recently proposed another subtype, the deficit syndrome, based on Kraepelin's clinical description. This differs from other proposed negative subtypes and refers to the presence or absence of prominent, enduring and primary negative symptoms. Primary negative symptoms have to be due to psychophrenia itself, in other words, independent of factors such as depression, anxiety, akinesia... Kirkpatrick et al. have proposed the Schedule for the Deficit Syndrome (SDS) to reliably identify this deficit syndrome. Some studies using this instrument have supported the validity of the deficit syndrome concept. Particularly, deficit patients have clinical, neuropsychological, neurological, eye-tracking and brain imaging impairments compared to nondeficit patients. We realized a french translation of SDS and used it to study a biological index (plasma homovanillic acid, pHVA) among deficit and nondeficit schizophrenic patients. Our data suggest a specific biochemical basis for the deficit syndrome, ie, significant lower mean pHVA levels with a lack of diurnal variation for deficit patients. The french version of SDS was validated by Kirkpatrick after english back translation. We present here our psychometric data regarding reliability (assessed by weighted and unweighted kappa coefficients) and cohesiveness of the construct (assessed by rank-order correlations of each negative symptoms with the other five, using Spearman's rho). These data are quite significant and in agreement with the SDS authors. PMID- 7988406 TI - [Survey for participation in therapeutic trials in psychiatry]. AB - In collaboration with the Sofres Institute, a two-phase population survey was conducted in 1991. During the first phase, 10,000 households representative of the French population and regularly surveyed by the Sofres Institute answered five questions by mail. The purpose was to identify subgroups regularly receiving psychotropic drugs and followed up by a physician. They were identified according to whether they used any of some 30 neuroleptic and antidepressant drugs, the most frequently prescribed in their class. According to their answers returned by post, the subjects were classified into three groups: regular psychotropic drug users followed by general practitioners, regular psychotropic drug users followed by specialists (these subjects being considered possibly more severely ill), and non users of these drugs, subjects considered as controls. In the second phase, a random sample of these groups received a detailed questionnaire including 14 questions related to clinical trials. In addition the same questionnaire was given to hospitalised patients in three different psychiatric units. Out of total of 958 subjects who received the detailed questionnaire, 712 answered (a 74% response rate). Results indicate that a majority of the subjects (50% to 74% depending on the subgroups) have already heard about the need for clinical trials to test new drugs. However, less than 20% of these subjects are aware of a recent French law protecting patient rights in clinical trials. This awareness appears to be quite insufficient A large number of subjects do not know whether they have been part of a clinical trial in the past.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7988407 TI - [The role of type 2 serotonin receptors, 5-HT2A and 5-HT2C, in depressive disorders: effect of medifoxamine]. AB - The serotonin (5-HT) is implicated in many centrally-regulated functions and has shown to be involved in affective disorders, such as depression and anxiety disorders. Recent progress in pharmacology and molecular neurobiology have confirmed the concept of the heterogeneity of 5-HT receptors and permitted reformulation of new hypothesis concerning antidepressant mechanisms of action, in particular those concerning serotoninergic receptors. Up to date, among the 5 HT defined sites, only 13 have been cloned, and several subfamilies have been described. Particularly, the 5-HT1 family containing receptors: 5-HT1A, 5 HT1B/1D, 5-HT1E and 5-HT1F. The 5-HT2 family includes receptors that stimulate phospholipase C: 5-HT2A (previously termed 5-HT2), 5-HT2B and 5-HT2C (previously termed 5-HT1C). Concerning 5-HT2 family, it is possible that some 5-HT binding drugs properties initially attributed to 5-HT2A receptors, might well be mediated by 5-HT2C receptors. Recently, medifoxamine (Cledial) activities on 5-HT systems have been shown. In particular, these activities are related on 5-HT2C and/or 5 HT2A binding sites. Results indicate that, in vitro, medifoxamine affinities (Ki) are near to 1 microM, for both 5-HT2C and 5-HT2A sites (ratio = 1.42). On the other hand, m-CPP, an 5-HT2C agonist, considered as a reference compound, has the same affinities that medifoxamine, but a higher one for 5-HT2A (ratio = 3.42). In animals models considered as predictive for psychotropic activity in human, we investigate in rat the impact of medifoxamine on 5-HT2C receptors, using Learned Helplessness model (LH) and the social interaction test.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7988408 TI - [Chemotherapy in Alzheimer's disease. Retrospective study in a specialized hospital center]. AB - In this study, our aim was to analyse the prescriptions of drugs used to improve Alzheimer's disease at CHS Paul Guiraud. This study was carried out a posteriori on 16 hospitalized patients. We have seen that for our patients there is no general rule, nor therapeutic scheme but the choice of treatment is carried out according to the professional experience of the physician. The treatment therefore is composed of symptomatic drugs alone or associated with etiologic drugs. Eleven anxiolytic or hypnotic drugs were prescribed. Alimemazine is the most prescribed in the sixteen cases. The preferential use of this drug can be explained by its presentation in the form of drops. In two cases, behavioural improvements were noted, in two other cases, we noted accentuation of dementia. Meprobamate used in seven cases of the sixteen, was never used alone. We find neuroleptics in fifteen of the sixteen cases studied: In seven cases they were administered from the beginning of the hospitalisation; for the others they were introduced later during a phase of agitation or delirium. On the whole, they were effective on aggressive agitation, in particular thioridazine. Eight of the patients, were treated with haloperidol. In two cases, the behaviour disorders were not stopped; in four cases, there was a worsening of dementia. We noted depression in 6 cases from the beginning of hospitalization, and two cases during hospitalization. The anti-depressive drugs besides their main effect, reduce also anxiety. In two cases, we observed an aggravation of disorientation and confusion following of the prescription of amitryptiline and mianserine.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7988409 TI - [Action and tolerance of dothiepin hydrochloride (Prothiaden) in depressive states during the evolution of psychotic disorders]. AB - During psychosis evolution, depressions occur frequently with a prevalence between 10% and 70% (average 25%-50%). Depression aggravates psychosis prognosis by increasing the risk of suicide, relapse and hospitalization. So antidepressant and neuroleptic treatments are often associated. Many studies with contradictory results were realized. Some concluded a favourable effect of this association, others considered this concomitant medication aggravates psychotic symptoms and adverse reactions. However this association appears to be efficient especially in deficitary or depressive forms of schizophrenia. The objective of this multicentre, non comparative, open study is to assess during 6 weeks the efficacy and tolerability of dothiepin in the treatment of depression occurring during the evolution of psychosis. The initial score on HDRS (17 items) had to be at least 18. 124 patients (40.7 years, 63.1% male) suffering from chronic psychosis associated with depressive syndrome were included in 29 hospital centres. According to DSM III-R criteria, 71.9% of patients were schizophrenic and 43% were suffering from major depressive illness. 16 patients (12.9%) stopped prematurely the treatment and side effects were reported for 8 of them. Any unexpected side effect occurred and pre-existing psychotic disorders reappeared for one patient. During the whole study, 63% of the population were treated with 75 mg as daily dosage of dothiepin. All concomitant treatments except antidepressant were authorized. 115 patients (95%) received at least one associated neuroleptic treatment and 54 patients (44.6%) a concomitant antiparkinsonian treatment. The significant decrease, between day 0 and day 45, of the global score on HDRS (from 23.78 to 8.48, p < 0.01), confirms the improvement of depression.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7988410 TI - Immunocytochemical localization of cytochromes P450 17 alpha-hydroxylase and aromatase in embryonic cell layers of elongating porcine blastocysts. AB - Localized expression of cytochromes P450 17 alpha-hydroxylase (P450c17) and aromatase (P450arom) was investigated in embryonic cell layers of elongating porcine blastocysts by immunocytochemistry. Blastocysts were flushed from the uterus on day 12 of pregnancy, fixed in paraformaldehyde, embedded in paraffin, sectioned, and stained using immunogold- and peroxidase-based techniques. Staining for both P450c17 and P450arom was intense in spherical 7- to 10-mm blastocysts, but was absent in earlier stage 2- to 4-mm blastocysts and less intense or absent in later stage 20-mm and filamentous embryos. Cytochrome P450c17 was limited to the trophoblast of all blastocysts expressing the enzyme, and in spherical 7- to 10-mm blastocysts, essentially all cells of the trophoblast layer stained positively for P450c17. However, as elongation became apparent in 10-mm blastocysts, the cells of the trophoblast became flattened, and the expression of P450c17 declined particularly in those trophoblast cells adjacent to the embryonic disc where mesoderm outgrowth was occurring. In fact, two distinct populations of trophoblast cells became obvious: one that maintained P450c17 expression, and one that did not. Moreover, those trophoblast cells expressing P450c17 were less flattened than neighboring cells in which P450c17 expression was absent. These two morphologically and functionally distinct trophoblastic cell populations were most obvious in areas furthest from the embryonic disc. Cytochrome P450arom was expressed in the trophoblast as well as the hypoblast under the embryonic disc. Neither P450c17 nor P450arom appeared to be expressed in the embryonic disc or the mesoderm of the expanding blastocyst. These functional and structural changes in the embryonic cell layers of the elongating conceptus may be associated with the transient synthesis and secretion of estrogen that occur at the time of maternal recognition of pregnancy in the pig. PMID- 7988411 TI - Exploring up-stream of the gonadotropin-releasing hormone receptor gene. PMID- 7988412 TI - Isolation and characterization of the 5'-flanking region of the mouse gonadotropin-releasing hormone receptor gene. AB - The GnRH receptor (GnRH-R) is a cell surface, G protein-coupled receptor that is highly expressed in pituitary gonadotropes. Activation of the receptor by GnRH stimulates the release of FSH and LH. Pituitary GnRH-R numbers and, hence, gonadotrope responsiveness to GnRH vary under different conditions and are regulated to a large extent by GnRH itself. To study the transcriptional regulation of the GnRH-R gene, a genomic clone containing 1.2 kilobases (kb) of the 5'-flanking region of mouse GnRH-R gene was isolated and characterized. A major transcriptional start site was identified 62 nucleotides upstream of the translational start site by primer extension and ribonuclease protection analyses. The promoter region does not contain canonical TATA sequences in the appropriate location. To determine whether this putative promoter is functional, it was subcloned into a luciferase reporter plasmid (GnRH-RLuc), and its transient expression was studied in cell lines of gonadotrope (alpha T3-1) and somatolactotrope (GH3) origins as well as those of nonpituitary origin (JEG-3 and CV-1). Luciferase activity was increased in alpha T3-1 (246-fold +/- 34.5-fold; P < 0.005) compared with the promoterless vector control but was considerably lower in GH3 (41-fold +/- 3.9-fold; P < 0.005), JEG-3 (12-fold +/- 0.9-fold; P < 0.005) and CV-1 (8-fold +/- 1.3-fold) indicating that GnRH-RLuc is preferentially expressed in cells of gonadotrope origin. Furthermore, GnRH agonist stimulated luciferase activity 3.4-fold +/- 0.3-fold (P < 0.005) above basal levels in GH3 cells cotransfected with rat GnRH-R complementary DNA, indicating that the GnRH-R promoter sequence is responsive to this ligand. In summary, we have identified and partially characterized the promoter region of the mouse GnRH-R and demonstrated that the regulatory elements for tissue-specific expression as well as for GnRH regulation are present within a 1.2-kb 5'-flanking region of the mouse GnRH-R gene. PMID- 7988413 TI - Localization and characterization of adenosine receptor expression in rat testis. AB - Adenosine has long been suspected to play an important role in regulating male reproduction. To determine the sites of adenosine action in testis, the distribution of a family of recently cloned adenosine receptors was examined in rats. Northern blot analysis and in situ hybridization studies revealed high levels of testicular A3 adenosine receptor messenger RNA and lower levels of A1 adenosine receptor messenger RNA. Neither A2a nor A2b adenosine receptor gene expression could be detected. In situ hybridization and comparative polymerase chain reaction studies showed high level A3 receptor gene expression in germ cells (spermatocytes and spermatids), whereas high levels of A1 receptor gene expression was seen in Sertoli cells. To test for the presence of functional A1 and A3 receptors, the regulation of adenylyl cyclase by adenosine analogs was examined in seminiferous tubules and spermatozoa. Treatment of seminiferous tubules with forskolin resulted in a 5-fold increase in cAMP levels. The A1/A3 receptor agonist iodo-N6-aminobenzyladenosine inhibited forskolin-stimulated cAMP levels in the presence of the A1 8-cyclopentyl-1,3-dipropylxanthine antagonist 8 cyclopentyl-1,3-dipropylxanthine, showing that functional A3 receptors were present. The A1-selective agonist N6-cyclopentyladenosine also inhibited forskolin-stimulated cAMP levels, showing that functional A1 receptors were present. Treatment of spermatozoa with forskolin resulted in a 2-fold increase in cAMP levels. However, neither iodo-N6-aminobenzyladenosine nor N6 cyclopentyladenosine altered basal or forskolin-stimulated cAMP levels in sperm. These data show that functional inhibitory adenosine receptors are widely distributed in testis, with different patterns of expression. PMID- 7988414 TI - Carbon monoxide as a novel neuroendocrine modulator: inhibition of stimulated corticotropin-releasing hormone release from acute rat hypothalamic explants. AB - Although recent evidence suggests that the gas nitric oxide (NO) can modulate the secretion of corticotropin-releasing hormone (CRH) from acute rat hypothalamic explants, another gas, carbon monoxide (CO), has been suggested to play a role in neural signaling in the brain; CO may complement the activity of NO in long term potentiation. In this study, we have investigated whether CO shares with NO the ability to modify the release of CRH from the rat hypothalamus. Hemin, a specific CO precursor through the enzyme heme oxygenase (the enzymatic pathway synthesizing endogenous CO), was found to inhibit in a dose-dependent manner KCl stimulated CRH release, with a maximal effect at 1 microM, while showing no effect on basal CRH secretion. The stimulation of CRH by interleukin-1 beta (100 ng/ml) was also significantly antagonized by hemin (1 microM). An inhibitor of heme oxygenase, zinc-protoporphyrin-9, had no effect on basal or stimulated CRH release up to a maximal dose of 10 microM. When hemin and zinc-protoporphyrin-9 were given together, the hemin-induced inhibition of CRH release was completely antagonized by the enzyme inhibitor. These findings provide evidence that endogenous CO may play a role in the control of CRH release; by analogy with NO, CO may represent a major new neuroendocrine modulator. PMID- 7988415 TI - Evidence for diverse roles of protein kinase-C in the inhibition of gene expression by insulin: the tyrosine aminotransferase, albumin, and phosphoenolpyruvate carboxykinase genes. AB - We have previously shown that insulin is less effective in inducing expression of several genes in H4 hepatoma cells with reduced functional protein kinase-C (PKC) activity. However, other reports suggest that insulin regulation of gene transcription is not PKC dependent. Insulin and phorbol 12-myristate 13-acetate (PMA) rapidly inhibit transcription of the tyrosine aminotransferase and albumin genes. Prolonged PMA pretreatment, to desensitize cells to PMA, resulted in a loss of insulin ability to inhibit albumin transcription. Insulin was still able to inhibit tyrosine aminotransferase transcription, but less than in non-PMA pretreated cells, and there was also a slight decrease in the ability of insulin to inhibit phosphoenolpyruvate carboxykinase transcription. We previously demonstrated decreased responsiveness of PMA-induced gene expression in insulin desensitized cells. In the present work, using insulin-desensitized H4 cells (insulin pretreatment for 24 h), subsequent treatment with PMA did not alter phosphoenolpyruvate carboxykinase transcription rates, whereas PMA did inhibit tyrosine aminotransferase transcription rates to an extent similar to observed in nonpretreated cells. Unexpectedly, there was a significant increase in albumin transcription after PMA addition to insulin-pretreated cells. These findings support our hypothesis that the role of PKC in the regulation of gene expression by insulin varies for different insulin-regulated genes. PMID- 7988417 TI - Enhancement of rat splenic lymphocyte mitogenesis after short term preexposure to corticosteroids in vitro. AB - Numerous previous studies investigating the effects of corticosteroids on immune proliferation reported almost unanimously inhibitory effects. However, in many of these studies, high concentrations of corticosteroids (micromolar range) and long incubation times (days) were used. We have investigated whether corticosteroid hormones at low physiological (nanomolar) vs. high (micromolar) concentrations have distinct effects on immune cells after short term (minutes) as opposed to long term preexposure (hours). When rat splenocytes were preincubated with high concentrations (0.1-1 microM) of corticosterone (CORT) or with the specific glucocorticoid agonist RU 28362 (0.1 microM) for 1-6 h, washed, and then exposed to the T-cell mitogen Concanavalin-A, a time- and dose-dependent inhibition of lymphocyte mitogenesis over the next 3 days of culture was found. Preincubation with the glucocorticoid antagonist RU 486 completely blocked this inhibitory effect of CORT and RU 28362. Preexposure of splenocytes to CORT for 10-60 min did not alter mitogenesis. No differences were observed between intact and adrenalectomized (ADX) rats. However, if splenocytes from ADX rats were used in the presence of the glucocorticoid antagonist RU 486, the proliferative response over a 3-day period was stimulated by short term preexposure (10-30 min) to low concentrations (3-30 nM) of CORT. Under these incubation conditions, the mineralocorticoid aldosterone, in the presence of RU 486; also produced a stimulatory effect on ADX splenic lymphocyte mitogenesis, whereas RU 28362 was not effective. Corticosteroid receptor binding studies revealed the presence of mineralocorticoid (MR) as well as glucocorticoid (GR) receptors (45 and 600 fmol/mg protein, respectively) in the spleen. In conclusion, low physiological concentrations of CORT and aldosterone have novel stimulatory properties on mitogenesis of splenic lymphocytes from ADX rats. These effects become evident in the presence of GR antagonist and persist after short corticosteroid preexposure times. In contrast, after prolonged preincubation with high concentrations of corticosteroids, the well known immunosuppressive action is observed. We postulate that distinct MR- and GR-mediated effects may underlie these differential steroid actions on splenic lymphocyte proliferation. PMID- 7988416 TI - Developmentally regulated expression of the preproinsulin gene in the chicken embryo during gastrulation and neurulation. AB - Despite the absence of a pancreas, which develops between embryonic day 3 (E3) to E4, previous studies showed that insulin receptors are widely expressed in chicken embryos from the blastoderm stage (unincubated embryo, E0) through gastrulation (E0.5-E1), neurulation (E1.5-E2), and organogenesis. We now characterize prepancreatic preproinsulin gene expression and its regulation, using a highly sensitive modification of the polymerase chain reaction. We found preproinsulin messenger RNA (mRNA) expression at all stages, from the unincubated chicken blastoderm through early organogenesis, with the highest expression in embryos undergoing gastrulation. In situ hybridization analysis of E1-E1.5 embryos in toto showed widespread distribution of preproinsulin mRNA in a pattern similar to that of insulin receptor mRNA. In contrast, insulin-like growth factor I mRNA expression appeared later than preproinsulin mRNA in the embryo; it was first demonstrable in the head portion of E3 and was found in head, trunk, and caudal regions by E4. With a novel culture system for chicken embryos during neurulation, we examined whether glucose regulated prepancreatic preproinsulin mRNA expression. Embryos cultured in glucose-free medium had increased preproinsulin mRNA with respect to the value in ovo, but the addition of 17 mM glucose had no stimulatory effect. In marked contrast, in organ cultures of E13 pancreas, insulin mRNA expression decreased in glucose-free medium by 50% relative to that in ovo. The addition of glucose restored the levels to a concentration similar to that found in ovo. Exogenous insulin added to cultured E1.5 embryos increased protein and DNA synthesis. We conclude that the preproinsulin gene is widely expressed in chicken embryo structures throughout gastrulation and neurulation. This prepancreatic preproinsulin mRNA is differentially regulated compared to the pancreatic mRNA. Preproinsulin gene products may have a role in cell proliferation, differentiation, or survival in very early avian embryos at a time when insulin-like growth factor-I expression is absent or undetectable. PMID- 7988418 TI - Corticotropin-releasing hormone mediates the response to cold stress in the neonatal rat without compensatory enhancement of the peptide's gene expression. AB - A variety of stressors activate the hypothalamic-pituitary-adrenal axis, with secretion and compensatory enhanced synthesis of hypothalamic corticotropin releasing hormone (CRH). Whether CRH is a major effector in the stress response of the neonatal rat and whether the peptide's gene expression is subsequently up regulated are not fully understood. We studied the effect of cold-separation stress on plasma corticosterone (CORT) levels and CRH messenger RNA (CRH-mRNA) abundance in the paraventricular nucleus. Rats (4-16 days old) were subjected to maximal tolerated cold-separation. CORT and CRH-mRNA abundance were measured before and at several time points after stress. Cold-separation stress resulted in a significant plasma CORT increase in all age groups studied. This was abolished by the administration of an antiserum to CRH on both postnatal days 6 and 9. CRH-mRNA increased in rats aged 9 days or older, but not in 6-day-old rats, by 4 h after stress. These results suggest the presence of robust CRH mediated adrenal responses to cold-separation stress in neonatal rats. Before postnatal day 9, however, the compensatory increase in CRH-mRNA abundance is minimal. PMID- 7988419 TI - Expression of the major isoenzyme of protein kinase-C in skeletal muscle, nPKC theta, varies with muscle type and in response to fructose-induced insulin resistance. AB - The ability of insulin to stimulate glucose uptake by skeletal muscle varies as a function of muscle type, but the biochemical mechanisms that regulate insulin mediated glucose transport under normal conditions and in pathological states of insulin resistance are poorly understood. We evaluated differences in the expression of nPKC theta (the major isoform of protein kinase-C in skeletal muscle) in hind limb muscles of different fiber type composition from normal Sprague-Dawley rats and rats made insulin resistant by feeding a fructose enriched diet. In total muscle homogenates from normal rats, the amount of nPKC theta per unit total protein quantified by immunoblotting using a specific antipeptide antibody was 2.5 times higher in pure white muscle (tensor fascia latae) compared with red muscle (soleus), with two mixed muscles showing intermediate expression. The development of insulin resistance after a fructose enriched diet was associated with significant increases in diacylglycerol and nPKC theta mass in the membrane fraction of tensor fascia latae, but fructose feeding had no effect on conventional PKC enzyme activity and immunoreactive protein. Thus, expression of nPKC theta varies as a function of muscle type, and fructose-induced insulin resistance appears to be associated with diacylglycerol mediated isoenzyme-specific changes in nPKC theta in white muscle. PMID- 7988420 TI - Characterization of thyroid hormone (T3) receptors in three osteosarcoma cell lines of distinct osteoblast phenotype: interactions among T3, vitamin D3, and retinoid signaling. AB - T3 is required for normal skeletal development, but its cellular targets in bone are unknown. T3 regulates target gene transcription via a specific nuclear receptor (T3R), which can heterodimerize with 9-cis-retinoic acid, 1 alpha, 25 dihydroxyvitamin D3, or retinoic acid receptors to modify T3 responsiveness. Serum-free cultures were developed to investigate hormone interactions in three osteosarcoma cell lines, ROS25/1, UMR106, and ROS17/2.8, that express fibroblast like, preosteoblast, and mature osteoblast phenotypes. ROS25/1 expressed T3R alpha 1, but only low levels of T3R beta 1, whereas UMR106 and ROS17/2.8 cells expressed both receptor proteins. All cells expressed c-erb-A alpha 2 protein and equal levels of 1 alpha,25-dihydroxyvitamin D3 receptor, 9-cis-retinoic acid receptor, and retinoic acid receptor messenger RNAs. Endogenous T3R activity and the effects of D3 and 9-cis-RA on T3 responsiveness were determined in transfections using reporter genes containing T3 response elements from rat malic enzyme or alpha-myosin heavy chain genes. Cell-specific T3 responses were associated with differing patterns of T3R gene expression and stages of osteoblast phenotype expression. A change in T3R beta 1 gene expression during osteoblast phenotype differentiation may modify T3 action in developing bone. PMID- 7988421 TI - Insulin delivery in nosedrops: new formulations containing alkylglycosides. AB - Insulin was administered to rats via nosedrops in the presence or absence of various alkylglycosides; systemic insulin absorption was measured as a fall in blood D-glucose concentration in animals made hyperglycemic by xylazine/ketamine anesthesia. Nosedrops (0.04 ml) containing alkylglycosides or regular porcine insulin alone were without effect. Nosedrops containing both a small amount of alkylglycoside (0.03-0.50%) and insulin (2 U regular porcine) caused a rapid decrease in blood D-glucose levels and a concomitant increase in serum immunoreactive insulin levels. The maximal hypoglycemic response was observed between 60 and 120 min after delivery of nosedrops. Decylmaltoside was less effective at enhancing systemic insulin absorption than dodecylmaltoside, tridecylmaltoside, or tetradecylmaltoside, whereas octylmaltoside was totally ineffective. Dodecylsucrose, a compound which differs from dodecylmaltoside only in one carbohydrate residue, had a similar effect on blood D-glucose values when it was included in the nosedrop formulation with insulin. Decylsucrose was considerably less potent than dodecylsucrose at enhancing systemic absorption of insulin. Nonylglucoside was effective at promoting insulin absorption from nosedrops only when used at higher doses (0.25-0.50%), whereas heptylglucoside and hexylglucoside were ineffective. These results indicated that nosedrops containing insulin plus an extremely low concentration (0.03%) of an absorption enhancing agent such as tetradecylmaltoside can be used to lower blood D-glucose values. PMID- 7988422 TI - A central negative feedback action of thyroid hormones on thyrotropin-releasing hormone secretion. AB - Two experiments were conducted to test the hypothesis that thyroid hormones exert central negative feedback effects on the secretion of TRH from the hypothalamus in the ewe. In the first experiment, we examined the effects of thyroidectomy on the secretion of TRH and TSH. Thyroidectomy was followed by an unambiguous increase in TRH in pituitary portal plasma and TSH in the peripheral circulation. In the second experiment, we tested the effects of T4 replacement to thyroidectomized ewes. T4 replacement reversed the effects of thyroidectomy on TRH and TSH release. Of interest, TRH secretion in thyroidectomized ewes was continuously elevated during the collection, raising the possibility that TRH is secreted continuously, rather than exclusively in a strictly pulsatile manner indicative of phasic discharges synchronized among TRH neurosecretory elements. Collectively, these results suggest that thyroid hormones can act centrally to inhibit TRH (and thus TSH) release in the ewe, and they support the concept that at least part of the negative feedback action of thyroid hormones is exerted at the hypothalamic level. PMID- 7988423 TI - Regulation of glucagon-like peptide-1-(7-36) amide secretion by intestinal neurotransmitters and hormones in the isolated vascularly perfused rat colon. AB - Glucagon-like peptide-1 (GLP-1) is promptly released from endocrine cells of the distal part of the gut after oral ingestion of a meal. To test the possibility that hormones produced by the proximal small intestine or transmitters of the enteric nervous system may be involved in the early phase of meal-induced GLP-1 secretion, various intestinal regulatory peptides and neurotransmitters of the gut were administered intraarterially in the isolated vascularly perfused rat colon preparation. The release of GLP-1 in the portal effluent was measured by a specific RIA. Intraarterial infusion of glucose-dependent insulinotropic peptide (GIP) over the concentration range 0.25-1 nM evoked a dose-dependent release of GLP-1, with a maximal response of 350% of the basal value. Tetrodotoxin did not modify the GIP-induced release of GLP-1. Secretin or cholecystokinin did not stimulate the secretion of GLP-1. Bombesin (10(-9)-10(-7) M) provoked a dose dependent release of GLP-1, consisting of an early peak, followed by a sustained response. Calcitonin gene-related peptide (5 x 10(-8) M) induced a dramatic rise of GLP-1 immunoreactivity in the portal effluent (peak at 800% of the basal value 10 min after the start of infusion). Similarly, the beta-adrenergic agonist isoproterenol at concentrations of 10(-7) and 10(-6) M provoked a pronounced release of GLP-1 (peak at 500% of the basal value with 10(-6) M isoproterenol). Finally, the muscarinic cholinergic agonist bethanechol at a concentration of 10( 4) M evoked a gradual increase in GLP-1 immunoreactivity, which reached a maximal value (900% over basal) at the end of the 30-min infusion period. The lowest concentration of bethanechol used in the present study (10(-5) M) did not increase portal GLP-1 immunoreactivity over the basal value. Tetrodotoxin did not modify the bethanechol-, isoproterenol-, calcitonin gene-related peptide-, or bombesin-induced GLP-1 release. In conclusion, the present study conducted with the isolated vascularly perfused rat colon shows that there are interactions between the two most potent incretins, GIP and GLP-1, probably through an enteroendocrine pathway. Additionally, several transmitters of the gut are potent stimulants of GLP-1 release and, therefore, represent potential tools in the treatment of the noninsulin-dependent diabetes mellitus. PMID- 7988424 TI - Fibroblast growth factor receptor type 1 expression during rat testicular development and its regulation in cultured Sertoli cells. AB - In the present study, we examined the ontogeny of the type 1 receptor for basic fibroblast growth factor (FGFR-1) in whole rat testis, its cellular localization, and its in vitro regulation in 20-day-old rat Sertoli cells. Gene expression of FGFR-1 was developmentally regulated; expression was higher in prepubertal testes and decreased with sexual maturity. The transcript was found to be expressed in Leydig-enriched fractions, peritubular cells, Sertoli cells, and, to a lesser extent, germ cells. FSH as well as (Bu)2cAMP enhanced FGFR-1 messenger RNA (mRNA) levels in cultured Sertoli cells, suggesting an involvement of the protein kinase A pathway. Addition of basic FGF (bFGF), tumor necrosis factor-alpha (TNF alpha), or interleukin-1 alpha resulted in a dose- and time-related increase in FGFR-1 mRNA levels. The effect of bFGF was specific, because it was neutralized by cotreatment with an anti-bFGF. We tested medium conditioned by germ cells and found a stimulation of the Sertoli cell FGFR-1 mRNA levels, which was abolished by immunodepletion of the conditioned medium with anti-TNF alpha antibodies. It is suggested that in Sertoli cells, bFGF action, when mediated by FGFR-1, is under a complex hormonal (FSH) and paracrine and/or autocrine control exerted at least by bFGF, TNF alpha, and interleukin-1 alpha. PMID- 7988425 TI - Insulin and epidermal growth factor influence guanine nucleotide-releasing factor by distinct mechanisms. AB - Both insulin and epidermal growth factor (EGF) significantly increased the activation of p21Ras in Rat-1 fibroblasts transfected with human insulin receptors. As both growth factors have been shown to stimulate guanine nucleotide exchange on p21Ras in permeabilized cells, we examined their effects on total cellular guanine nucleotide exchange factor (GEF) activity in a direct assay, using the rate of dissociation of [3H]GDP from p21Ras as a measure of GEF activity. Insulin increased GEF activity in a time-dependent manner, whereas EGF had no effect on GEF activity at any time point studied. To assess whether EGF stimulates guanine nucleotide exchange by recruiting Grb-2-Sos complexes to the plasma membrane, we measured GEF activity in both the cytosol and the plasma membrane fractions of the insulin- and EGF-treated cells. Insulin increased GEF activity in both fractions (48 +/- 12% [3H]GDP released vs. 24 +/- 6% in control plasma membranes, and 65 +/- 13% vs. 13 +/- 4% in control cytosolic fractions), whereas EGF enhanced only the plasma membrane-associated activity (43 +/- 12% of [3H]GDP release in the plasma membrane fraction and 10 +/- 2% in the cytosol). Western blotting of the subcellular fractions with Grb-2 and Sos antibodies revealed translocation of these elements to the plasma membrane after stimulation of cells with either insulin or EGF. Thus, whereas insulin stimulates guanine nucleotide exchange on Ras by both translocating Grb-2-Sos complexes to the plasma membrane and increasing the GEF activity of Sos, EGF does so by causing a translocation of Grb-2-Sos without increasing GEF activity. PMID- 7988426 TI - Insulin inhibits dephosphorylation of adenosine 3',5'-monophosphate response element-binding protein/activating transcription factor-1: effect on nuclear phosphoserine phosphatase-2a. AB - We examined the effects of insulin on the phosphorylation state of cAMP response element-binding protein (CREB) in normal rat adipocytes. Insulin increased in vivo phosphorylation of CREB by 40%. Although both phosphoprotein phosphatase-1 and -2A dephosphorylate CREB and activating transcription factor-1, insulin action appears to be mediated via its strong inhibitory effect on nuclear phosphatase-2A (PP-2A) activity. Using in vitro protein kinase-A-phosphorylated activating transcription factor-1 as a substrate, we found that insulin inhibited nuclear PP-2A activity by 80% (P < 0.001), which represents approximately 50% of the total nuclear phosphatase activity. Greater than 50% of the effect of insulin was observed at 0.3 nM and 2 min of exposure. These findings are the first indicator that a signal initiated by a cell surface tyrosine kinase receptor may regulate nuclear PP-2A activity and thereby affect the phosphorylation state of transcription factors. PMID- 7988427 TI - The effect of glucocorticoid on the synthesis of biglycan and decorin in human osteoblasts and bone marrow stromal cells. AB - We have previously demonstrated that glucocorticoids induce differentiation of human bone marrow stromal cells (BMSC) into cells expressing mature osteoblast phenotype. As glucocorticoids have marked effects on extracellular matrix protein synthesis in bone, and because proteoglycans are important components of bone matrix and may condition the differentiation and biological activities of osteoblasts, we studied the effects of dexamethasone (Dex) on the synthesis of small proteoglycans [decorin (DCN) and biglycan (BGN)] in adult human BMSC and human osteoblasts (HOB). First passaged HOB and BMSC were treated with either ethanol or 10(-7) M Dex for 7 days. After treatment, the cells were metabolically labeled with either [35S]SO4 alone or [35S]SO4 and [3H]leucine together for 24 h. Conditioned media were collected, and cell layers were extracted with 4 M guanidine HCl. The extracts and conditioned media were subjected to gel filtration and ion exchange chromatography. Fractions containing radiolabeled proteoglycans were analyzed either directly or after immunoprecipitation by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Dex treatment resulted in a dramatic increase in DCN and an associated decrease in BGN in both the conditioned medium and the cell layer of HOB cultures. In Dex-treated BMSC cultures, BGN was decreased in both the conditioned medium and cell layer, whereas DCN was stimulated in the majority of cultures. Northern blot analysis indicated that steady state messenger RNA (mRNA) concentration of DCN was increased by Dex in all of the HOB cultures and in seven of eight BMSC cultures analyzed. The steady state mRNA level of BGN was decreased by Dex in both HOB and BMSC cultures. The regulation of DCN and BGN mRNA by Dex in both HOB and BMSC (when responsive) was dose dependent. Time-course analysis indicated that as little as 1 day of treatment with Dex was sufficient to decrease BGN mRNA and increase DCN mRNA (when observed) levels in BMSC; the regulation spanned a 4-week interval, during which the extracellular matrix of BMSC was mineralized. The effect of Dex on the steady state mRNA levels of DCN and BGN in HOB was also apparent after 1 day of treatment. These accumulated results suggest that Dex modulates the synthesis of small proteoglycans in both human bone marrow stromal osteoprogenitor cells and mature osteoblasts. PMID- 7988428 TI - Generation of des-(1-3) insulin-like growth factor-I in serum by an acid protease. AB - Des-(1-3) insulin-like growth factor-I (IGF-I), a more potent IGF-I variant, has been isolated from biological fluids and tissue extracts. The mechanisms involved in this posttranslational modification of IGF-I have not been elucidated. In this study we demonstrated the presence in rat serum of an acid protease activity that is capable of generating des-(1-3) IGF-I from intact IGF-I. An assay for measuring this enzyme activity using an immobilized synthetic substrate, biotin-G P-E-T-L-C, that includes the site of cleavage of intact IGF-I was developed. Using this assay, the time, temperature, and pH dependency of the enzyme activity was investigated. Although some activity was observed under neutral conditions, the optimal pH was pH 5.5. Of a variety of commercially available proteases tested, only trypsin and cathepsin-D had activity. In contrast to the serum enzyme activity, trypsin was more active at pH 7.5 than at pH 5.5, and cathepsin D resulted in extensive proteolysis of IGF-I. Soybean trypsin inhibitor, alpha 1 antitrypsin, and pepstatin-A were able to partially inhibit the serum enzyme activity. This enzymatic activity was partially purified from serum by acid ethanol extraction (6-fold) and further purified by pepstatin-A affinity chromatography (200-fold). The partially purified enzyme had characteristics similar to those of the activity measured in serum. The enzymatic conversion of [125I]IGF-I to [125I]des-(1-3) IGF-I in serum was confirmed by immunoprecipitation using antibody to an N-terminal fragment of IGF-I (residues 1 9), which could recognize intact IGF-I, but not des-(1-3) IGF-I (< 3% cross reactivity), and by size-exclusion HPLC analysis. When [125I]IGF-I was incubated with serum, only the 7.5-kilodalton free IGF-I fraction contained the des-(1-3) IGF-I variant. [125I]des-(1-3) IGF-I was not detected in the 150- to 200- or 50 kilodalton IGF-I-binding protein complexes. These findings demonstrate that des (1-3) IGF-I can be generated in serum at neutral pH and that this process may be enhanced under the acidic conditions that occur in the pericellular environment. PMID- 7988429 TI - Gastrin-releasing peptide is produced in the pregnant ovine uterus. AB - Our previous finding of appreciable quantities of a gastrin-releasing peptide (GRP)-like immunoreactive (GRPLI) entity in ovine fetal and maternal plasma led us to examine the ovine pregnant uterus as a possible source of this material. At term, intense immunohistochemical staining for GRPLI occurred in the endometrial epithelial cells, and the term ovine uterus also contained abundant GRP messenger RNA (mRNA). In contrast, GRP mRNA was not detected in fetal membranes. GRP mRNA was present in the uterus on gestational day 63; a significant increase in GRP mRNA had occurred by day 100. Thereafter, levels remained elevated until term, but 3 months postpartum, GRP mRNA levels were greatly reduced. As previous studies suggested the GRPLI entity to be of greater molecular size than GRP-(1 27), we deduced the primary structure of ovine uterus GRP by sequencing a complementary DNA clone isolated from a complementary DNA library constructed from term ovine uterus polyadenylated RNA. Ovine uterine GRP is composed of 27 amino acid residues and has a conserved C-terminal region, similar to GRP structures in other species. We conclude that during pregnancy, the ovine uterus produces considerable quantities of GRP, which may play an important but hitherto unrecognized role in utero-placental development and possibly in fetal development after transfer to the fetus. PMID- 7988431 TI - Structure-activity relationship of adrenomedullin, a novel vasodilatory peptide, in cultured rat vascular smooth muscle cells. AB - Vascular smooth muscle cells (VSMC) from rat aorta possess specific receptors for a novel potent vasorelaxant peptide, adrenomedullin (AM). To elucidate its receptor coupling to guanine nucleotide-binding stimulatory protein and the structural requirement of the AM molecule to its vascular receptors, we have studied the effects of guanine nucleotides on [125I]human (h) AM binding and adenylate cyclase activity in cultured rat VSMC, and the effects of various synthetic hAM analogs on [125I]hAM binding and the cAMP response. Guanosine 5'-O (3-thiotriphosphate) dose dependently inhibited [125I]hAM binding to rat VSMC membranes. hAM stimulated adenylate cyclase activity, and its effect was additive with GTP. hAM-induced cAMP formation was abrogated by pretreatment with cholera toxin, but not by that with pertussis toxin. Intact hAM-(1-52)-NH2 and N-terminal truncated derivatives [hAM-(13-52)-NH2, hAM-(16-52)-NH2] almost equally inhibited [125I]hAM binding and stimulated cAMP formation, whereas removal of C-terminal Tyr52 residue [hAM-(1-51)-NH2] remarkably decreased receptor-binding activity and the cAMP response. The effects of hAM-(1-52)-OH, hAM-(1-51)-OH, and a linear hAM analog ([carbamoylmethyl-Cys16,21]hAM-NH2) were far less potent on receptor binding and the cAMP response than that of hAM-(1-52)-NH2. The C-terminal fragment [hAM-(33-52)-NH2] and the N-terminal fragment [hAM-(1-10)-OH] had neither receptor-binding nor adenylate cyclase activity. hAM-(22-52)-NH2 had no agonistic effect, but showed an antagonistic effect on the hAM-induced cAMP response. These data suggest that vascular AM receptors are functionally coupled to adenylate cyclase via guanine nucleotide-binding stimulatory protein. Studies of the structure-activity relationship of hAM revealed that the cyclic structure formed by the disulfide bridge and amidation of the C-terminal residue of the AM molecule are critical for receptor binding and subsequent cAMP generation and suggest that the C-terminal fragment hAM-(22-52)-NH2 may be an antagonist for vascular AM receptors. PMID- 7988430 TI - Target gene activation by 1,25-dihydroxyvitamin D3 in osteosarcoma cells is independent of calcium influx. AB - Analogs of the seco-steroid hormone, 1,25-dihydroxyvitamin D3 [1,25-(OH)-2D3] can preferentially stimulate genomic or nongenomic signaling pathways in osteoblasts. In this study, we used 1,25-(OH)2D3 analogs and voltage-sensitive Ca2+ channel (VSCC) ligands, including dihydropyridines (Bay K 8644 and nitrendipine), in an osteosarcoma cell model to examine the relationship between 1,25-(OH)2D3 stimulated Ca2+ influx and genomic and nongenomic pathways leading to osteoblast activation. Northern blotting experiments demonstrated that an analog of 1,25 (OH)2D3, 1,24-dihydroxy-22-ene-24-cyclopropyl D3, increased messenger RNA (mRNA) levels of both osteopontin (OPN) and osteocalcin (OCN) without triggering Ca2+ influx through VSCCs. Nitrendipine (an inhibitor of L-type VSCCs) did not block the mRNA increase induced by either analog 1,24-dihydroxy-22-ene-24-cyclopropyl D3 or 1,25-(OH)2D3. 1-Deoxy analogs of 1,25-(OH)2D3, 25-hydroxy-16-ene-23-yne-D3, or 25-hydroxy-23-yne-D3, which stimulate Ca2+ influx, did not produce mRNA accumulation for OPN and OCN, consistent with their poor binding to nuclear receptors. Likewise, Bay K 8644, an agonist of VSCCs that produces Ca2+ influx, did not increase mRNA levels for OPN or OCN. Experiments using a construct derived from the sequence of the genomic OPN promoter region and a luciferase reporter confirmed the analog specificity in stimulating transcription. Together these results indicate that 1,25-(OH)2D3-mediated up-regulation of genes encoding OPN and OCN is independent of Ca2+ influx and suggest that the stimulation of Ca2+ influx by 1,25-(OH)2D3 is not required for target gene activation. PMID- 7988432 TI - Glucocorticoids potentiate the action of atrial natriuretic polypeptide in adrenalectomized rats. AB - Adrenal insufficiency in human and rat is associated with an impairment of the diuretic response to water load, and only glucorticoids (GCs) restore this deficit. Our observation that GCs potentiate atrial natriuretic polypeptide (ANP) stimulated cGMP production in cultured renal cells prompted us to examine the possibility that GCs may restore the diuretic response through the potentiation of ANP action. Initially, changes in urine volume and ANP levels were studied in adrenalectomized (Adx) and sham-operated intact rats after an oral water load of 5 ml/100 g BW. Urine volume after water load was 4.5 +/- 0.5 ml/30 min in the intact rats, whereas it was 0.8 +/- 0.2 ml/30 min in the Adx rats. In the intact rats, a significant increase in plasma ANP level was observed 30 min after the water load, whereas no increase was observed in Adx rats. This defective ANP response may be involved in the impairment of the diuretic response in Adx rats. Indeed, pretreatment of Adx rats with dexamethasone (Dex, 20 micrograms/100 g BW) increased plasma ANP levels even before water load and improved diuretic response. Subsequently, effect of iv administration of human or rat ANP at a pharmacological dose (2.5 micrograms/100 g BW) on urine volume, osmolarity, and urinary excretion of cGMP, and sodium was studied in Adx rats that received an oral water load 30 min before ANP. Dex treatment was achieved by per os administration 3 h before the ANP injection. In Adx rats, the urine volume after ANP administration was 1.2 +/- 0.1 ml/30 min, and pretreatment with Dex markedly increased the urine volume to 6.3 +/- 0.4 ml/30 min. Dex also increased ANP induced osmolar and sodium excretion by 2.6- and 2.9-fold, respectively. Although urinary excretion of cGMP was increased in Adx rats by ANP administration, a further significant increase was observed by the pretreatment with Dex. Injection of (Bu)2cGMP to Adx rats pretreated with Dex resulted in a significant increase in urine volume and osmolar and sodium excretion. However, no significant increase in urine volume was observed in Adx rats not pretreated with Dex. The present study suggests that GCs restore the diuretic response to acute water load not only by increasing the secretion of ANP but also by potentiating ANP stimulated cGMP production. Furthermore, GCs may augment ANP action at one or more steps other than cGMP formation because administration of (Bu)2cGMP to Adx rats did not correct the diuretic response to water load. PMID- 7988433 TI - Hypothalamic-pituitary-adrenal activity during chronic central administration of interleukin-2. AB - The cytokine interleukin-2 (IL-2) exerts numerous effects within the immune as well as the central nervous system and is thought to serve as a humoral signal in their communication. Brain-derived or blood-borne IL-2 may also control the activity of the hypothalamic-pituitary-adrenal (HPA) axis at various levels of regulation. In this study we investigated whether persistently elevated levels of central IL-2, which are associated with several diseases or induced during immunotherapeutic use of this cytokine, could induce long term activation of the HPA axis. Adult male Sprague-Dawley rats received an intracerebroventricular infusion of the recombinant cytokine at a rate of 5 U/h (equivalent to 2.5 ng/h or 162 fmol/h) by means of osmotic minipumps. Control animals received heat inactivated IL-2. After 7 days of continuous infusion, blood samples were taken at intervals of 4 h over a period of 24 h, and plasma levels of ACTH and corticosterone (CORT) were determined. IL-2 caused a significant increase in ACTH levels during the later portion of the dark phase of the cycle. Plasma CORT concentrations were significantly elevated over almost the whole diurnal cycle. Measurements of CORT-binding globulin concentrations revealed IL-2-induced decreases during the dark phase, resulting in a marked increase in free CORT. Additionally, after 11 days of chronic infusion, both groups of animals underwent a 20-min restraint stress. IL-2-treated animals showed stress-induced increases in plasma ACTH and CORT that were not significantly different from those of animals treated with heat-inactivated IL-2. Along with the alteration of HPA activity seen in the IL-2-treated animals, chronic delivery of the cytokine caused periventricular tissue damage and gliosis. Taken together, the data reflect the capacity of IL-2 to modulate neuroendocrine activity over an extended period of treatment. Moreover, the IL-2-induced effects on HPA activity seen here may help to explain some of the endocrine disturbances seen in patients undergoing IL-2 immunotherapy. PMID- 7988434 TI - Pregnancy increases guanosine 3',5'-monophosphate in the myometrium independent of nitric oxide synthesis. AB - The mechanism for myometrial quiescence during pregnancy is unknown. cGMP plays an integral role in the relaxation of smooth muscle, and nitric oxide (NO) is the most important endogenous activator of soluble guanylate cyclase. The purpose of this study was to determine the effect of gestational age on myometrial cGMP and NO synthase (NOS) activity in the guinea pig. Myometrial cGMP content (measured by RIA) rose slowly until 0.49 (fraction of pregnancy completed) gestation before abruptly increasing to 200 times the non-pregnant control value. It then declined precipitously after 0.87 gestation. Of the known isoenzymes of NOS, the messenger RNAs coding for both endothelial and neuronal NOS could be amplified from the myometrium of pregnant and nonpregnant animals using reverse transcriptase polymerase chain reaction, but inducible NOS messenger RNA was not found. Myometrial calcium-dependent NOS activity (measured by the conversion of L-[U 14C]arginine to [U-14C]citrulline) declined slowly with advancing gestation (r2 = 0.096; slope = -0.34; P = 0.01), but never differed significantly from the activity in nonpregnant animals [31.1 +/- 11 (term pregnancy) vs. 56.9 +/- 16 (nonpregnant) pmol/min.g; P = NS]. Calcium-independent activity declined shortly after conception, and then rose toward the nonpregnant level (r2 = 0.19; slope = 0.45; P = 0.0009). However, at no time was it significantly different from that in the nonpregnant animal. Pregnancy had no effect on myometrial L-arginine and L citrulline content. The administration of L-nitro-arginine methyl ester (200 mg/kg) to inhibit NOS dramatically increased blood pressure and reduced fetal renal NOS activity, but had no effect on the myometrial cGMP content. Estradiol (500 micrograms/kg for 5 days) modestly increased cGMP, but in contrast to many tissues in which estradiol increases NOS, it had no effect on myometrial NOS activity. We conclude that pregnancy dramatically increases cGMP by a mechanism independent of NOS. The stimulus remains to be identified. The temporal change in cGMP concentration is consistent with the hypothesis that cGMP mediates myometrial quiescence during pregnancy. PMID- 7988435 TI - Follicle-stimulating hormone increases the expression of tissue inhibitors of metalloproteinases TIMP-1 and TIMP-2 and induces TIMP-1 AP-1 site binding complex(es) in prepubertal rat Sertoli cells. AB - Primary cultures of prepubertal rat Sertoli cells secrete two major tissue inhibitors of metalloproteinases: TIMP-1 (M(r) 28K) and TIMP-2 (M(r) 21 K). FSH stimulated Sertoli cell TIMP-1 and TIMP-2 activity in a time- and dose-dependent manner and also stimulated TIMP-1 and TIMP-2 protein and messenger RNA levels. These effects were mimicked by the cAMP analog, 8-bromo-cAMP, and the phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine. The protein kinase C activating phorbol ester phorbol myristate acetate (TPA) stimulated TIMP-1 but not TIMP-2 activity and messenger RNA levels. Cycloheximide and actinomycin-D inhibited basal TIMP-1 and TIMP-2 activity and inhibited the ability of FSH, 8 bromo-cAMP, and TPA to stimulate TIMP activity. The protein kinase A (PKA) inhibitor AMP Rp isomer did not affect basal TIMP-1 and TIMP-2 activity or TPA stimulated TIMP-1 activity. However, the PKA inhibitor markedly reduced FSH and 3 isobutyl-1-methylxanthine stimulation of TIMP-1 and TIMP-2 activity. FSH, 8-bromo cAMP, and TPA stimuli induced DNA binding complexes capable of binding to a TIMP 1 AP-1 site consensus sequence oligonucleotide. The AP-1 site binding complex(es) induced by all three treatments reacted with antibodies directed broadly against fos and jun protooncogene families and against the specific family members c-fos, junB, and junD but not c-jun proteins. Constitutive cAMP response element binding activity capable of binding an artificial cAMP response element binding site oligonucleotide was demonstrated in Sertoli cell nuclear extracts. This activity was minimally modulated by FSH, 8-bromo-cAMP, or TPA treatment. In summary, Sertoli cells secrete TIMP-1 and TIMP-2 that can be coordinately up-regulated by FSH through a cAMP, PKA-dependent pathway. a convergence of TPA, FSH, and cAMP mediated signals in prepubertal Sertoli cells may occur with the induction of specific AP-1 site binding complex(es) containing jun and fos proteins. Our data suggest that FSH stimulation of TIMP-2 expression may be regulated independently to that of TIMP-1. We propose that the ability of FSH to stimulate Sertoli cell TIMP activity suggests a central role for this hormone in the control of extracellular matrix turnover during testicular development at the level of metalloproteinase inhibition. PMID- 7988436 TI - Relative contribution of phosphoinositides and phosphatidylcholine hydrolysis to the actions of carbamylcholine, thyrotropin (TSH), and phorbol esters on dog thyroid slices: regulation of cytidine monophosphate-phosphatidic acid accumulation and phospholipase-D activity. I. Actions of carbamylcholine, calcium ionophores, and TSH. AB - The actions of carbamylcholine (Cchol), the ionophores A23187 and thapsigargin, and TSH on [3H]cytidine monophosphate-phosphatidic acid ([3H]CAMP-PA) accumulation were studied in prelabeled dog thyroid slices to evaluate phosphatidic acid (PA) generation and inositol recycling by phosphatidylinositol (PtdIns) synthesis. The effects of the same agonists were also measured on phosphatidylbutanol generation in [3H]palmitate- or [3H]myristate-prelabeled slices to assess the activity of phospholipase-D (PLD) and on the effluxes of myo [3H]inositol and [3H]choline induced by these agents from prelabeled slices. Cchol (10(-6)-10(-4) M) increased inositol phosphate (InsP) generation, with no change in inositol efflux, and contracted the intracellular inositol pool. This suggests a stimulation of PtdIns synthesis as well as hydrolysis. The muscarinic agonist provoked a dramatic accumulation of CMP-PA in the presence of lithium chloride (10 mM), which suggests that when InsP hydrolysis is inhibited, inositol limits the rate of CMP-PA incorporation into PtdIns. Cchol also increased phosphatidylbutanol formation. The latter two actions of Cchol were reproduced by A23187 (10(-5) M) and thapsigargin (2 x 10(-6) M) and were inhibited by calphostin-C, an inhibitor of the regulatory site of protein kinase-C. Cchol also induced increased free choline efflux, with a decreased choline phosphate relative content of the medium. TSH (10 mU/ml) stimulated free inositol efflux and induced a slight and proportional increase in [3H]inositol incorporation in phosphoinositides and InsP. The hormone also increased PA and CMP-PA accumulation exclusively in the presence of the PA phosphatase inhibitor propranolol (10(-4) M), but had no detectable action on PLD activity. None of these effects of TSH was reproduced by forskolin or potentiated by lithium chloride (10 mM). The data demonstrate the existence in thyroid tissue of a PLD-hydrolyzing phosphatidylcholine that was stimulated by Cchol and increased intracellular Ca2+, but not by TSH. The results obtained, besides confirming that TSH does not stimulate PtdInsP2-PLC or affect phosphatidylcholine hydrolysis, suggest that the hormone, instead, stimulates de novo PtdIns synthesis and/or inositol transport. The physiological relevance of these actions of Cchol, increased intracellular Ca2+, and TSH in thyroid metabolism could be related to their divergent effects on thyroid cell metabolism. PMID- 7988437 TI - Relative contribution of phosphoinositides and phosphatidylcholine hydrolysis to the actions of carbamylcholine, thyrotropin, and phorbol esters on dog thyroid slices: regulation of cytidine monophosphate-phosphatidic acid accumulation and phospholipase-D activity. II. Actions of phorbol esters. AB - The effects of phorbol dibutyrate (PDBu) on phosphatidylbutanol (PtdBut) generation in [3H]palmitate- or [3H]myristate-prelabeled dog thyroid slices were measured to assess the activity of phospholipase-D (PLD) in the presence or absence of the two inhibitors of protein kinase-C (PKC), staurosporine (STSP) and calphostin-C. The actions of the same agents on [3H]cytidine monophosphate phosphatidic acid accumulation were also determined to evaluate phosphatidic (PA) generation and inositol recycling to phosphatidylinositol. The effluxes of [3H]choline and [3H]ethanolamine induced by the phorbol ester from prelabeled slices were also evaluated. PDBu (5 x 10(-9) to 5 x 10(-6) M) potently stimulated PLD activity, with a concomitant increase in fatty acids incorporation in phosphatidylcholine (PtdCho). However, under no condition did the phorbol ester result in cytidine monophosphate-phosphatidic acid accumulation. It stimulated the efflux of choline and ethanolamine while decreasing choline and ethanolamine phosphates in the slices and incubation medium. Calphostin-C, inhibiting PKC, decreased PtdBut and PtdCho formation induced by the phorbol ester, as opposed to STSP (5 x 10(-6) M), which did not affect these actions of PDBu and, moreover, reproduced by itself the effects of the phorbol ester on choline efflux and PtdBut generation despite efficient inhibition of other effects of PKC. These data demonstrate the existence in thyroid tissue of a PLD-hydrolyzing PtdCho, which was stimulated by phorbol esters and STSP. They also suggest that the PA formed after PKC stimulation and subsequent PLD activation is channeled toward PtdCho resynthesis when intracellular Ca2+ is not increased, whereas the PA accumulated with a concomitant increase in intracellular Ca2+ is diverted toward phosphatidylinositol synthesis. The physiological relevance of this Ca independent stimulation of a PKC-coupled PLD in thyroid metabolism could be related to the growth-inducing and dedifferentiating effects of the phorbol esters. PMID- 7988438 TI - Effects of insulin on protein kinase-C (PKC) in HIRC-B cells: specific activation of PKC epsilon and its resistance to phorbol ester-induced down-regulation. AB - We evaluated the role of protein kinase-C (PKC) during insulin action in HIRC-B cells. Insulin provoked rapid increases in 1) diacylglycerol; 2) translocation of PKC epsilon, but not PKC alpha, PKC delta, or PKC zeta, from the cytosol to the membrane fraction; 3) membrane PKC enzyme activity; and 4) phosphorylation of immunoprecipitable 80-kilodalton (kDa) myristylated alanine-rich C-kinase substrate (MARCKS) protein and heat-stable 80-kDa protein (also probably MARCKS). Phorbol esters stimulated the translocation of PKC alpha and PKC delta as well as PKC epsilon, but not PKC zeta. The effects of phorbol esters on 80-kDa MARCKS phosphorylation were approximately 4 times as strong as those of insulin. Treatment of HIRC-B cells with phorbol esters for 20-24 h resulted in complete loss of immunoreactive PKC alpha and PKC delta in cytosol and membrane fractions, but substantial amounts of PKC epsilon were persistently translocated to the membrane fraction of down-regulated cells. This persistently translocated, residual PKC epsilon in down-regulated cells was associated with increased basal hexose uptake, but this was not due to PKC activation, as it was not inhibited by the PKC inhibitor, RO 31-8220. Acute insulin treatment, on the other hand, increased hexose uptake in down-regulated cells, and this insulin-stimulated uptake was inhibited by RO 31-8220 in down-regulated cells as well as in nondown regulated cells. Insulin also stimulated the phosphorylation of the heat-stable 80-kDa protein in down-regulated cells, suggesting that the residual PKC epsilon in these cells can be activated by insulin. PMID- 7988439 TI - Identification of relaxin gene expression and protein localization in the uterine endometrium during early pregnancy in the pig. AB - The corpus luteum is the primary source of circulating relaxin (RLX) in female pigs. However, a preliminary experiment in our laboratory identified RLX in the uterine endometrium of a day 16 pregnant gilt that had been ovariectomized on day 8 of pregnancy, and the pregnancy maintained via progesterone replacement therapy. Therefore, our objective was to examine the uterus as a potential extraovarian source of RLX during the estrous cycle and early pregnancy in pigs. Reproductive tissues were collected from pregnant (n > or = 3/day) and nonpregnant (n > or = 3/day) gilts on days 10 (n = 6), 12 (n = 6), 14 (n = 6), 16 (n = 8), 18 (n = 6), and 20 (n = 6) of the estrous cycle and pregnancy and on day 42 (n = 2) of gestation. To verify that the RLX identified in uterine tissues was not of ovarian origin, three additional pregnant gilts were ovariectomized on day 8, and the pregnancy was maintained by progesterone replacement therapy until day 16, when the reproductive tissues were collected for immunohistochemistry. The uterine tissues were scored for specific RLX immunostaining and analyzed for the effects day and pregnancy by analysis of variance. Within the uterine endometrium, the luminal epithelium of pregnant pigs contained more RLX than that of nonpregnant pigs (P < or = 0.001). However, there was no difference in either the glandular epithelium or stromal tissues (P > or = 0.10). Increased RLX in the luminal epithelium of pregnant pigs was detected on both days 18 (P < or = 0.05) and 20 (P < or = 0.001) of gestation compared to that in nonpregnant pigs on similar days of the estrous cycle. An effect of day was also observed for RLX immunostaining in the luminal epithelium (P < or = 0.005), but not in glandular or stromal tissues (P > or = 0.10). In both pregnant and nonpregnant pigs, luminal epithelial RLX immunostaining was faint on days 10-12. Thereafter, RLX immunostaining increased on day 14 to reach peak levels on day 16. In nonpregnant pigs, RLX immunostaining dropped to low levels on day 18 and became faint to absent by day 20 of the estrous cycle. In pregnant pigs, RLX immunostaining remained elevated, but appeared to decline slightly by day 20 and became undetectable by day 42 of gestation. RLX immunolocalization in the glandular epithelium was detected on all days in pregnant and nonpregnant pigs, whereas stromal-specific immunostaining was not observed.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 7988441 TI - Epithelial cell localization of type 2 11 beta-hydroxysteroid dehydrogenase in rat and human colon. AB - 11 beta-Hydroxysteroid dehydrogenase (11 beta HSD), by catalyzing the interconversion of active corticosterone (B) to inactive 11-dehydrocorticosterone (A) in the rat and cortisol (F) to cortisone in man, maintains normal in vivo specificity of the mineralocorticoid receptor (MR) in both kidney and distal colon. Two isoforms of 11 beta HSD have been reported: the cloned type I, NADP(H) dependent 11 beta-dehydrogenase/oxo-reductase, and a high affinity NAD+-dependent 11 beta-dehydrogenase (type 2 isoform). Previous studies indicate that the MR in the distal colon is localized to ion-transporting surface epithelial cells and non-epithelial neuroendocrine cells within the lamina propria. We have now analyzed the expression and activity of 11 beta HSD in specific cells isolated from both rat and human colonic mucosa by a chemical shear and microdissection method. Both isoforms of 11 beta HSD were detected in rat and human colonic mucosa. Type 2 11 beta HSD activity, with an apparent Km (mean +/- SE) of 56.3 +/ 2.2 nM for B in the rat and 35.3 +/- 1.2 nM for F in man, was exclusively localized to surface and crypt epithelial cells. In contrast, the type I isoform in the rat, with an apparent Km of 0.95 +/- 0.14 microM for B, was localized exclusively to specific nonepithelial cells in the lamina propria. Human colon type I 11 beta HSD, however, which has an apparent Km for F of 0.51 +/- 0.04 microM, was present in both the lamina propria and the surface epithelium. Northern blot analysis of rat colonic RNA using a 32P-labeled complementary DNA probe for rat type I 11 beta HSD confirmed the presence of type I 11 beta HSD messenger RNA in intact distal colon mucosa, but failed to detect 11 beta HSD messenger RNA in surface epithelial cells. In conclusion, abundant levels of a high affinity NAD(+)-dependent type 2 11 beta HSD isoform are expressed in both rat and human colon. Colonic type 2 11 beta HSD is kinetically distinct from the low affinity NADP-dependent type I isoform, behaves predominantly as a dehydrogenase, is localized exclusively to the ion-transporting epithelia, and is likely to be the product of a second 11 beta HSD gene. Furthermore, the spatially distinct patterns of expression of these isoforms suggest that in vivo there are two physiologically distinct populations of MR in the colon: the aldosterone selective MR in the epithelium and the nonselective MR in the nonepithelial cells within the lamina propria. PMID- 7988440 TI - Induction of vasoactive intestinal peptide gene expression and prolactin secretion by insulin-like growth factor I in rat pituitary cells: evidence for an autoparacrine regulatory system. AB - The effects of recombinant human insulin-like growth factor I (IGF-I) on both vasoactive intestinal peptide (VIP) and PRL production and gene expression were studied using rat anterior pituitary cell cultures grown in serum-free defined medium. We also examined whether pituitary VIP could be involved in the PRL response to IGF-I and hence in a paracrine regulatory system. Exposure of cultured anterior pituitary cells to IGF-I (2.6 nM) for 3 h caused a significant decrease in both VIP content and media PRL. Treatment with IGF-I (from 0.65-5.2 nM) for 48 h increased VIP production and VIP messenger RNA (mRNA) accumulation, whereas only an increase in media and intracellular PRL content without changes in mRNA was observed. In all these experiments, IGF-I led to a decrease in both GH secretion and expression. Immunoglobulins G purified from VIP antiserum inhibited IGF-I-induced PRL release without affecting intracellular and mRNA levels. The inhibition of both GH secretion and gene expression induced by IGF-I was not blocked by VIP antiserum. In conclusion, these results indicate that IGF I induces VIP gene expression, and its secretion and also increases PRL secretion. The effect of IGF-I on PRL release is specifically mediated by VIP through a paracrine or autocrine mechanism. PMID- 7988442 TI - Retinoic acid stimulates interstitial collagenase messenger ribonucleic acid in osteosarcoma cells. AB - The rat osteoblastic osteosarcoma cell line UMR 106-01 secretes interstitial collagenase in response to retinoic acid (RA). The present study demonstrates by Northern blot analysis that RA causes an increase in collagenase messenger RNA (mRNA) at 6 h, which is maximal at 24 h (20.5 times basal) and declines toward basal level by 72 h. This stimulation is dose dependent, with a maximal response at 5 x 10(-7) M RA. Nuclear run-on assays show a greater than 20-fold increase in the rate of collagenase mRNA transcription between 12-24 h after RA treatment. Cycloheximide blocks RA stimulation of collagenase mRNA, demonstrating the need for de novo protein synthesis. RA not only causes an increase in collagenase secretion, but is known to decrease collagen synthesis in UMR 106-01 cells. In this study, the increase in collagenase mRNA is accompanied by a concomitant decrease in the level of alpha 1(I) procollagen mRNA, which is maximal at 24 h (70% decrease), with a return to near-control levels by 72 h. Nuclear run-on assays demonstrated that the decrease in alpha 1 (I) procollagen expression does not have a statistically significant transcriptional component. RA did not statistically decrease the stability of alpha 1 (I) procollagen mRNA (calculated t1/2 = 8.06 +/- 0.30 and 9.01 +/- 0.62 h in the presence and absence of RA, respectively). However, transcription and stability together probably contribute to the major decrease in stable alpha 1 (I) procollagen mRNA observed. Cycloheximide treatment inhibits basal level alpha 1 (I) procollagen mRNA accumulation, demonstrating the need for on-going protein synthesis to maintain basal expression of this gene. PMID- 7988443 TI - Blockade of alpha 2-adrenoceptors stimulates basal and stress-induced adrenocorticotropin secretion in the developing rat through a central mechanism independent from corticotropin-releasing factor and arginine vasopressin. AB - In the neonatal rat, the response of the hypothalamo-pituitary-adrenal axis to stressful stimuli is markedly reduced during the first 2 weeks of life [stress hyporesponsive period (SHRP)]. In this report, we studied the effect of idazoxan (an alpha 2-adrenergic antagonist) on plasma ACTH and corticosterone levels in 8 day-old rats. Indeed, it is known that in the adult rat, blockade of alpha 2 adrenoceptors increases ACTH secretion stimulated by CRF and arginine vasopressin (AVP) injection. Injection of 2.5 micrograms/g idazoxan induced a rapid (within 30 min) increase in basal plasma ACTH and corticosterone levels that lasted for 60 min. Injection of increasing doses of idazoxan led to a dose-dependent stimulation of ACTH and corticosterone levels. Administration of 2.5 micrograms/g idazoxan significantly increased the ACTH response to insulin-induced hypoglycemia, whereas it potentiated and accelerated the ACTH response to ether exposure stress. We next examined ACTH secretion from superfused anterior pituitary glands. Neither the alpha 2-adrenergic agonist clonidine nor idazoxan changed the basal ACTH secretory rate. Idazoxan had no effect on CRF- and AVP stimulated ACTH secretion. This indicates that in vivo, idazoxan acts at a suprapituitary level. To investigate a possible effect of idazoxan on presynaptic alpha 2-adrenoceptors, we studied the effect of idazoxan on the concentrations of norepinephrine (NE) and L-DOPA in punches of locus coeruleus after dopa decarboxylase blockade. Idazoxan injection induced a decrease in the NE content, without changing L-DOPA levels, indicating that idazoxan can act at the level of presynaptic alpha 2-adrenoceptors, inducing an increased release and/or degradation of NE without any effect on catecholamines synthesis. Finally, we investigated a possible involvement of CRF and AVP in mediating the effect of alpha 2-adrenoceptor blockade on ACTH secretion. Passive immunization against CRF or AVP did not change the ACTH response to idazoxan administration, whereas idazoxan pretreatment had simply an additive effect on CRF- and lysine vasopressin-stimulated ACTH secretion. In conclusion, our data demonstrate that during the SHRP, blockade of alpha 2-adrenoceptors induces an increase in both basal and stress-induced ACTH secretion. They suggest that a decreased catecholaminergic tone, consecutive to an increased occupation of alpha 2 adrenoceptors, acting through a central mechanism independent from CRF and AVP may be responsible for the SHRP in the developing rat. PMID- 7988444 TI - Evidence that p21ras mediates the neurotrophic effects of insulin and insulin like growth factor I in chick forebrain neurons. AB - Insulin and insulin-like growth factors (IGF-I and IGF-II) support the survival and differentiation of many types of neurons, including those from fetal chick forebrain. The mechanisms by which these peptides exert their neurotrophic actions are poorly understood. The aims of this study were to determine if insulin and IGF-I activate p21ras in fetal chick forebrain neurons and if activation of p21ras mediates the neurotrophic actions of these peptides. Activation of neuronal p21ras was examined by measuring the amount of GTP bound to p21ras before and after growth factor treatment. Insulin and IGF-I increased the ratio of GTP/GTP + GDP by 31 +/- 9.0% and 36 +/- 8.0%, respectively, p21Ras activation by insulin and IGF-I was maximal within 5 min. In the presence of insulin the response was sustained out to 180 min, whereas the response to IGF-I decreased significantly by 180 min. Both peptides stimulated p21ras at low concentrations with a maximal response obtained at 10 ng/ml for each peptide, idicating that insulin and IGF-I activate ras by interacting with their homologous receptor. Pretreatment of neurons with lovastatin (2 micrograms/ml), an inhibitor of ras isoprenylation, completely blocked the activation of p21ras by insulin and IGF-I. Lovastatin also blocked the ability of these growth factors to support the survival and differentiation of fetal chick neurons in culture. We conclude that insulin and IGF-I activate p21ras in fetal chick forebrain neurons by increasing the amount of GTP bound to p21ras. The activation of neuronal p21ras is necessary for insulin and IGF-I to promote survival and differentiation in these neurons. PMID- 7988445 TI - Disproportional bone growth and reduced weight gain in gonadectomized male bovine growth hormone transgenic and normal mice. AB - Sex steroids have been shown to influence longitudinal bone growth during sexual maturation, partially by increased GH secretion. Mice transgenic for metallothionein promoter bovine GH were developed by pronuclear injection as a model with sex steroid-independent GH secretion. Prepubertal normal and transgenic, male and female mice were either gonadectomized or sham operated. The growth was divided into two segments: peripubertal growth from 30-60 days of age and adult growth from 60-90 days of age. Orchidectomy resulted in a decreased growth rate of the lumbar spine and a decreased weight gain during the peripubertal growth, whereas tibia growth was unaffected. The alteration in proportions between the lumbar spine and the tibia was apparent for both normal and bovine GH transgenic mice, suggesting that the effect was not mediated via decreased GH secretion. Orchidectomy resulted in increased adult tibial growth, whereas weight gain and lumbar growth were unaffected. In female mice, gonadectomy did not influence these parameters during either time period studied. In summary, we present data indicating that the male gonads in a GH secretion independent manner stimulate pubertal growth of the spine and inhibit the tibial growth of adult animals. PMID- 7988447 TI - Down-regulation of parathyroid (PTH)/PTH-related peptide receptor immunoreactivity and PTH binding in opossum kidney cells by PTH and dexamethasone. AB - Recent data have shown that PTH down-regulation of its receptor on opossum kidney (OK) cells is not associated with any change in the steady state level of the PTH/PTH-related peptide (PTHrP) receptor messenger RNA. For analysis of down regulation of the PTH/PTHrP receptor in OK cells, the present work uses a specific receptor anti-serum, SR-2, that is useful for detection and quantification of PTH/PTHrP receptor immunoreactivity on intact cells bearing the opossum PTH/PTHrP receptor. SR-2 specifically binds to COS-7 cells transiently expressing the opossum PTH/PTHrP receptor complementary DNA (OK-O), to LLCPK1 cells stably expressing the recombinant opossum PTH/PTHrP receptor (AOK cells), and to OK cells expressing endogenous PTH/PTHrP receptors, but not to mock transfected COS-7 cells or untransfected LLCPK1 cells. SR-2 binding was also linearly correlated with PTH binding in COS-7 cells transfected with different amounts of OK-O plasmid DNA. Treatment with PTH (100 nM) for 4 and 6 h did not significantly down-regulate the PTH/PTHrP receptor immunoreactivity, although PTH binding was decreased to 51% and 49% of control, respectively, and PTH-stimulated cAMP accumulation was decreased to 27% and 28% of control, respectively. Treatment with PTH (100 nM) for 24 and 48 h significantly decreased PTH binding to 51% and 60% of control and decreased PTH/PTHrP receptor immunoreactivity to 68% and 58% of control, respectively. Incubation of OK cells with 0.1 nM to 1 microM PTH for 4 h did not down-regulate the PTH/PTHrP receptor immunoreactivity, although PTH binding was decreased dramatically. Scatchard blot analysis revealed that the binding affinity was decreased by 7-fold in OK cells treated with PTH for 4 h without change in receptor number. Conversely, treatment of OK cells with PTH for 24 h resulted in a parallel decrease in both receptor number and receptor immunoreactivity without any change in receptor binding affinity. Treatment of OK cells with dexamethasone (0.1 nM to 1 microM) had no effect on PTH binding or PTH/PTHrP receptor immunoreactivity. Incubation of OK cells with both dexamethasone (1 microM) and PTH (0.1 nM to 1 microM), however, caused a significantly greater down-regulation of both PTH binding and PTH/PTHrP receptor immunoreactivity than in cells treated with PTH alone. These data indicate that during the first 4 h of exposure of OK cells to PTH, PTH/PTHrP receptors remain on the cell surface but have lowered affinity to bind the ligand and that dexamethasone potentiates the effect of PTH on PTH/PTHrP receptor down-regulation in OK cells. PMID- 7988446 TI - Activation of the baboon fetal pituitary-adrenocortical axis at midgestation by estrogen: enhancement of fetal pituitary proopiomelanocortin messenger ribonucleic acid expression. AB - We have proposed that estrogen, via regulation of placental metabolism of maternal cortisol, regulates the baboon fetal hypothalamic-pituitary-adrenal axis and the timing of the onset of de novo cortisol production. In support of this hypothesis, we demonstrated that the ontogenesis of fetal adrenal steroidogenic enzymes near term could be induced at midgestation by maternal estrogen treatment. In the present study, we determined whether maturation of the fetal adrenal near term and at midgestation after estrogen treatment reflects enhanced expression of the messenger RNA (mRNA) for the ACTH precursor molecule POMC. Fetal pituitaries were obtained on day 100 (n = 7) and day 165 (n = 5) of gestation (term = day 184) from untreated baboons and on day 100 after maternal treatment with estradiolbenzoate (sc; days 70-100; n = 6). Sections were fixed in paraformaldehyde and hybridized with saturating concentrations of an antisense (or sense) oligodeoxynucleotide complementary to bases 297-326 of human POMC mRNA that was 3' end-labeled with [35S]dATP. After stringent washes, sections were placed against Kodak X-Omat film (Eastman Kodak, Rochester, NY) and then dipped in Kodak NTB-2, developed, and counterstained. POMC mRNA (antisense minus sense) was quantified by densitometry and image analysis of silver grains. Specificity of labeling was documented by selective distribution of grains over a dispersed population of cells in sections of anterior pituitary hybridized with antisense, the relative absence of grains in sections incubated with sense, and the absence of grains in neurohypophyseal sections incubated with antisense. Moreover, silver grains were not visible when sections were pretreated with excess radioinert probe. The mean (+/- SE) maternal serum estradiol concentration in baboons treated with estradiol benzoate at midgestation (2.9 +/- 0.4 ng/ml) was greater (P < 0.05) than that in untreated baboons on day 100 (1.0 +/- 0.3) but not significantly different from that in late gestation (1.9 +/- 0.3). In umbilical serum, estradiol concentrations were greater (P < 0.05) at term (3.7 +/- 0.9) than at midgestation (0.7 +/- 0.2) but, unlike maternal values, were not significantly increased at midgestation after treatment of the mother with estradiol (1.1 +/- 0.2). Based on densitometric analysis, mean (+/- SE) pituitary POMC mRNA (absorbance units) was greater (P < 0.05) in baboon fetuses at term (0.57 +/- 0.05) than at midgestation (0.28 +/- 0.03) and increased (P < 0.05) on day 100 (0.43 +/- 0.04) in estrogen-treated animals. Similar results were obtained when data were analyzed as the number of silver grains/0.025 mm2.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 7988448 TI - Identification of deoxyribonucleic acid sequences that bind retinoid-X receptor gamma with high affinity. AB - The retinoid-X receptor (RXR) family (-alpha, -beta and -gamma) forms homodimers that bind to a number of retinoid-X response elements and trans-activate gene expression in a retinoid-dependent manner. Although, the RXRs are known to bind tandem direct repeats (DR) of the hexamer, RGGTCA, separated by 1 nucleotide, it is not known whether these represent the optimal and/or only recognition sequences. We, therefore, used a nonbiased strategy to identify sequences that efficiently bound RXR gamma, an isoform preferentially expressed in cardiac and skeletal muscle tissue. We performed binding site selection with bacterially expressed RXR gamma bound to glutathione-agarose and a pool of random sequences to derive a consensus DNA-binding site for RXR gamma. We analyzed a total of 41 individually selected oligonucleotides and found that RXR gamma bound with high affinity to motifs that were accommodated by the consensus AARGRNCAAAGGTCAA/cR. We observed that the majority of the sequences that formed complexes with RXR gamma in electrophoretic mobility shift analysis were DR-1 motifs; however, DR- motifs separated by 2, 4, and 8 nucleotides and a palindrome-0 motif were also demonstrated to interact with RXR gamma. Mutagenesis of the derived sequences indicated that both RGGTCA motifs were required for high affinity binding to RXR gamma. These derived sequences conferred appropriate 9-cis- and all-trans retinoic acid (RA) responses to a thymidine kinase promoter. Furthermore, supershift experiments with a RXR antibody verified that these sequences specifically interacted with RXR in nuclear extracts derived from C2C12 muscle cells. In conclusion, this study rigorously defines the range of DR motifs that can recognize RXR and regulate gene expression in a RA-dependent fashion. The derived consensus accommodates retinoid-X response elements that have been identified in a diverse range of genes trans-activated by 9-cis-RA via the RXR family. PMID- 7988449 TI - Testosterone promotes the conversion of round spermatids between stages VII and VIII of the rat spermatogenic cycle. AB - Several spermatogenic cell types have been reported to be responsive to testosterone (T) in vivo. We have proposed that the principal action of T is to facilitate the maturation of round to elongated spermatids during spermiogenesis. To identify T-dependent cell types during spermiogenesis, round spermatid populations were counted using stereological techniques in adult rats after T withdrawal and replacement. The number of round spermatids per testis in stages I III, IV-VI, VII, and VIII of the spermatogenic cycle were determined and, based on the known duration of each stage, the hourly production rates of round spermatid populations calculated. Sprague-Dawley rats received 3 cm T and 0.4 cm estradiol implants (TE treatment) for 11 weeks to suppress LH, testicular T levels, and spermatogenesis. To restore sperm production, high-dose T (24 cm) implants were then given, and animals were perfused 0, 2, 4, and 7 days later. Total testicular T levels were suppressed to 2.9% of control levels by TE treatment and significantly increased (P < 0.05) after 2 days of high-dose T, to remain between 7-12% of control. The hourly production rates of round spermatids between stages I and VII were suppressed to 29-35% of control by TE treatment and remained unchanged by high-dose T administration. Stage VIII round spermatid hourly production rates however, were markedly reduced to 5% of control by TE treatment and increased significantly (P < 0.05) to 27% of control after 4 days of high-dose T. The efficiency of conversion of spermatids through spermiogenesis was estimated from the ratios of the hourly production rates of successive spermatid groups. The conversion of spermatids between stages I-VII of the cycle did not differ from control regardless of the treatment. However, the conversion of round spermatids between stages VII and VIII was markedly suppressed to 16% of control by TE treatment and was then normalized after 4 days of high-dose T administration. We conclude that the conversion of round spermatids between stages VII and VIII is a highly T-dependent step during spermiogenesis. PMID- 7988450 TI - 17 beta-estradiol, but not 5 alpha-dihydrotestosterone, augments antibodies to double-stranded deoxyribonucleic acid in nonautoimmune C57BL/6J mice. AB - The influence of sex hormones on the immune response to foreign antigens as well as self-antigens is now recognized. In this study, we investigated the influence of gender and sex hormones on the development of antibodies to double-stranded DNA in nonautoimmune C57BL/6J mice. Immunoglobulin G (IgG) anti-dsDNA antibodies are commonly present in lupus patients and several autoimmune disease-prone murine strains. We found that C57BL/6J mice have detectable antibodies (IgM and IgG, but not IgA) to dsDNA. Interestingly, the incidence and level of IgG anti dsDNA antibodies were lower in male than in female mice. Orchidectomy or administration of 5 alpha-dihydrotestosterone to orchidectomized male mice had minimal effects on these antibodies. In contrast, administration of 17 beta estradiol to orchidectomized or intact males significantly increased both the incidence and levels of anti-dsDNA antibodies. In female mice, ovariectomy decreased whereas administration of estrogen augmented the incidence and levels of anti-dsDNA antibodies in ovariectomized as well as intact female mice. Kinetic studies revealed that estrogen treatment of male and female mice induced earlier and sustained expression of IgG anti-dsDNA antibodies compared to controls. IgG subisotype analysis showed IgG2b to be predominant. In summary, our findings suggest that estrogen, but not dihydrotestosterone, promotes anti-dsDNA antibodies in normal mice. PMID- 7988451 TI - Steroid binding and metabolism in the luteinizing hormone-releasing hormone producing neuronal cell line GT1-1. AB - LHRH synthesis and release are modulated in vivo by gonadal steroids. Although immunocytochemical and autoradiographic studies failed to detect appreciable amounts of estrogen or androgen receptor in LHRH-producing neurons, the recent finding that the promoter region of the LHRH gene contains several steroid hormone-responsive elements indicates a possible direct effect of sex steroids on these specialized neurons. The immortalized LHRH-producing neuronal cell line, GT1, which became recently available, may allow the study of LHRH dynamics. The presence of specific binding sites for estrogen and androgens as well as the presence of the two major enzymatic pathways involved in modulation of androgen action (the 5 alpha-reductase/3 alpha-hydroxysteroid dehydrogenase and the aromatase) have been studied in the GT1-1 clone. High affinity, low capacity binding sites for [3H]estradiol (Kd, 0.11 nM; binding capacity, 6.2 fmol/mg protein) and for a ligand of the androgen receptor, [3H]R1881 (Kd, 0.054 nM; binding capacity, 9.58 fmol/mg protein), have been identified in this cell line. A 2-fold induction of androgen-binding sites has been observed after 3 days of treatment of GT1-1 cells with estradiol (1 microM), indicating that the estradiol binding is probably linked to a functional estrogen receptor. Aromatase and 5 alpha-reductase/3 alpha-hydroxysteroid dehydrogenase activities have been also tested in GT1-1 cells. Under the culture conditions adopted, no detectable aromatization of [1 beta 3H]delta 4-androstenedione to estrone was observed using the tritiated water method. On the other hand, GT1-1 cells efficiently converted testosterone into dihydrotestosterone and subsequently into 5 alpha-androstan-3 alpha,17 beta-diol. In conclusion, GT1-1 cells possess several elements of the machinery through which sex steroids may influence LHRH dynamics. PMID- 7988452 TI - Regulation of 17 beta-hydroxysteroid dehydrogenase type 1 by epidermal growth factor and transforming growth factor-alpha in choriocarcinoma cells. AB - 17 beta-Hydroxysteroid dehydrogenase type 1 (17HSD type 1) is a steroidogenic enzyme that catalyzes the reversible interconversion of estrone and estradiol. In this study, we investigated the roles of epidermal growth factor (EGF) and tumor growth factor-alpha (TGF alpha) in the regulation of 17HSD type 1 gene expression and catalytic activity in cultured JAR, JEG-3, and BeWo choriocarcinoma cells. EGF and TGF alpha increased 17HSD type 1 protein concentrations in JAR and JEG-3 cells, as measured by time-resolved immunofluorometric assay, and 17HSD catalytic activity, as determined by production of estradiol from estrone. These increases were accompanied by parallel increases in concentrations of the 1.3-kilobase messenger RNA coding for 17HSD type 1 in these cells. EGF receptor tyrosine kinase activity inhibitors, tyrphostins, inhibited EGF action in JEG-3 cells, indicating that tyrosine kinase activity is needed for stimulation of the 17HSD type 1 gene. Treatment with 8-bromo-cAMP or phorbol 12-myristate 13-acetate increased the amount of 17HSD type 1 protein. Furthermore, phorbol 12-myristate 13-acetate potentiated the stimulatory effect of EGF. These results suggest that EGF and/or TGF alpha may play an important role in 17HSD type 1 regulation and, consequently, in estrogen production in the human placenta. PMID- 7988453 TI - Cloning and characterization of a mouse brain calcitonin receptor complementary deoxyribonucleic acid and mapping of the calcitonin receptor gene. AB - We have identified and characterized a mouse brain calcitonin receptor (CTR) complementary DNA (cDNA). This cDNA encodes a receptor protein that, after expression, has high affinity binding for salmon calcitonin (Kd approximately, 12.5 nM) and is coupled to adenylate cyclase. The binding affinity of this expressed receptor for salmon calcitonin is lower than that described for the previously cloned porcine renal and human ovarian CTRs, but is similar to that of the recently described rat brain CTR, designated the C1b form of the receptor. Analysis of the deduced structure of the mouse brain CTR reveals that it is highly related to the other CTR cDNAs that belong to a distinct family of G protein-coupled receptors with seven transmembrane-spanning domains. The major structural feature that distinguishes the mouse cDNA clone from the other CTRs is the presence of a consecutive 111-basepair nucleotide sequence that encodes a 37 amino acid sequence which is predicted to localize to the first extracellular loop between the second and third transmembrane-spanning domains. We have mapped the CTR gene in the mouse to the proximal region of chromosome 6, which is homologous to the 7q region of human chromosome 7; only a single CTR gene was identified. Preliminary analysis of the mouse CTR gene reveals that it is complex, consisting of multiple exons separated by lengthy introns that would allow for splice variants consistent with the existence of multiple CTR isoforms predicted from the CTR cDNA clones. The differential cellular and tissue distribution of these functionally distinct CTR isoforms provides the molecular basis for the previously reported widespread distribution and functional heterogeneity of the CTR. PMID- 7988455 TI - Regulation of human placental lactogen expression by 1,25-dihydroxyvitamin D3. AB - The human placenta synthesizes 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3] and expresses the vitamin D receptor (VDR), but the roles of 1,25-(OH)2D3 and the VDR in placental physiology are poorly understood. In this study, we have demonstrated that 1,25-(OH)2D3 stimulates the synthesis and release of human placental lactogen (hPL), one of the major secretory products of syncytiotrophoblast cells. Enzymatically dispersed trophoblast cells from term placentas exposed continuously to 1,25-(OH)2D3 (0.1, 6, and 37 microM) for 5 days released significantly more hPL than control cells after the third day of exposure. On days 4 and 5, the amounts of hPL released by cells exposed to 1,25 (OH)2D3 were 2.54- and 4.14-fold that of control cells (P < 0.001 in each instance). The stimulation by 1,25-(OH)2D3 was dose dependent and was accompanied by stimulation of hPL messenger RNA levels. Transient transfection studies of BeWo choriocarcinoma cells transfected with hPL promoter constructs coupled to the chloramphenicol acetyltransferase reporter gene indicated that the stimulation of hPL expression is due at least in part to stimulation of hPL gene expression. Deletion analysis studies of the hPL promoter indicated that a region between -500 to -1200 basepairs is necessary for 1,25-(OH)2D3 responsiveness. Analysis of this region shows a consensus vitamin D response element (VDRE) DNA binding site of a direct repeat motif separated by three bases. Ligation of this placental VDRE site into a heterologous chloramphenicol acetyltransferase vector caused 1,25-(OH)2D3 responsiveness. Moreover, mobility shift assays demonstrated binding of VDR to placental VDRE. These results indicate that 1,25-(OH)2D3 stimulates the synthesis and release of hPL by a mechanism involving hPL gene transcription and support a role for vitamin D and the VDR in placental function. PMID- 7988454 TI - Alpha-adrenergic receptors mediate the hypertriglyceridemia induced by endotoxin, but not tumor necrosis factor, in rats. AB - We assessed the role of catecholamines in mediating the hypertriglyceridemia induced by lipopolysaccharide (LPS) or tumor necrosis factor-alpha (TNF alpha) in rats by employing specific adrenoreceptor antagonists. Pretreatment with phentolamine, an alpha-antagonist, but not propranolol, a beta-antagonist, suppressed the hypertriglyceridemia induced by either low dose LPS (100 ng/100 g BW) or high dose LPS (50 micrograms/100 g BW). Prazosin, an alpha 1-selective antagonist, significantly suppressed the low dose LPS-induced hypertriglyceridemia by inhibiting hepatic triglyceride secretion, but did not affect the increase in lipolysis. In contrast, yohimbine, an alpha 2-selective antagonist, partially suppressed the high dose LPS-induced hypertriglyceridemia by inhibiting the decrease in postheparin lipoprotein lipase activity. Treatment with phentolamine and propranolol did not affect the hypertriglyceridemia induced by TNF alpha. In summary, these findings suggest that catecholamines via alpha adrenergic, but not beta-adrenergic, receptors are mediators of the hypertriglyceridemia induced by either low or high dose LPS in rats. alpha 1 Adrenergic receptors are involved in mediating the increased hepatic triglyceride secretion induced by low dose LPS, whereas alpha 2-adrenergic receptors are involved in mediating the decrease in lipoprotein lipase activity induced by high dose LPS. The hypertriglyceridemia induced by either low or high dose LPS may be regulated by a mechanism unrelated to TNF alpha in rats. PMID- 7988456 TI - Receptor binding and signal transduction are dissociable functions requiring different sites on follicle-stimulating hormone. AB - Separate sites for glycoprotein hormone receptor binding and signal transduction have yet to be elucidated. In general, certain peptide regions are thought to be critical for receptor binding, whereas the oligosacharides are thought to be important for signal transduction. Using site-directed mutagenesis of FSH, we made selective amino acid substitutions and oligosaccharide alterations to try and identify specific sites mediating receptor binding distinct from signal transduction and vice versa. We substituted Lys or Asp for beta Arg35 in the purported receptor binding loop between cysteine-32 and -51, and we substituted Gln for alpha Asn52, alpha Asn78, beta Asn7, or beta Asn24, the attachment sites for each of the oligosaccharide side-chains. We determined the binding and signal transducing activity of wild-type and mutant human FSH at the human FSH receptor, as recent data suggest that glycoprotein hormone-receptor interactions are species specific. The binding activities of FSH with Lys or Asp substituted for beta Arg35 were reduced 71% and 98%, respectively, but their signal transduction, at equivalent levels of binding activity, was unaffected. The binding activity of FSH lacking the oligosaccharide at alpha Asn52 was enhanced 2- to 3-fold, but its signal-transducing activity, at equivalent levels of receptor binding, was decreased 72%. In contrast, the binding and signal-transducing activities of FSH lacking the alpha Asn78, or alpha Asn7, or beta Asn24 oligosaccharide were unaffected. Thus, a specific amino acid (beta Arg35) is important for high affinity binding, but is not involved in signal transduction, whereas a specific oligosaccharide (alpha Asn52) is important for signal transduction, but is not required for high affinity binding. Therefore, receptor binding and signal transduction are dissociable functions involving different sites on the FSH glycoprotein. PMID- 7988457 TI - Two receptors for vasoactive intestinal polypeptide with similar specificity and complementary distributions. AB - Vasoactive intestinal polypeptide (VIP) has a variety of physiological effects. Pharmacological evidence suggesting that VIP acts via multiple receptors has been confirmed by the cloning of two VIP receptors (VIP1 and VIP2) with very different amino acid sequences. At both the VIP1 and the VIP2 receptor VIP, PHI, PACAP38, and PACAP27 have similar potency to each other. Only the VIP1 receptor is activated by secretin. The messenger RNAs (mRNAs) for the two receptors have completely different distributions as mapped by in situ hybridization histochemistry. VIP1 receptor mRNA is predominantly found in the lung, small intestine, thymus, and within the brain in the cerebral cortex and hippocampus. VIP2 receptor mRNA is present in a number of areas where VIP acts but VIP1 receptor mRNA is not present, including the stomach and testes. In the CNS VIP2 receptor mRNA is exclusively present in areas associated with neuroendocrine function, including several hypothalamic nuclei. In the periphery, it is also present in the pituitary and in pancreatic islets. PMID- 7988458 TI - Gender differences in the metabolic response to graded numbers of transplanted islets of Langerhans. AB - Gender differences after treatment with streptozotocin (STZ) have been previously reported; however, differences in the glucose response to islet transplantation in STZ-induced diabetes in male and female rats after islet transplantation have not been examined. Male and female Wistar-Furth rats were made diabetic using STZ (55 mg/kg BW) and then given an intraportal islet transplant. Control animals received sham injections and sham transplant surgery; diabetic animals received STZ and sham surgery. In male animals, islet grafts contained 0 (diabetic), 250, 500, 1000, 1500, 2000, and 3000 islets; in female rats, grafts were made up of 0, 500 700, 750, 1000, or 2500 islets. STZ treatment had more dramatic effects on male than female rats. During the diabetic phase, body weights of male rats were significantly reduced compared to those of control male animals; this was not observed among females. Although all STZ-treated animals were hyperglycemic, plasma glucose levels in male diabetic rats were significantly higher than those in females during this phase (29.8 +/- 2.1 vs. 24.6 +/- 0.6 mM). After islet transplantation, body weight gain was positively associated with the number of islets transplanted in male rats (r2 = 0.59; P < 0.01), but not in females (r2 = 0.09; P > 0.8). In both male and female rats, animals that received 1000 islets or more were generally normoglycemic by 3 weeks posttransplant (males, 10.8 +/- 2.2 mM; females, 7.1 +/- 0.2 mM). Approximately 60% of male and female animals that received 500 islets achieved a reduction in plasma glucose levels. Mean plasma glucose levels were 17.2 +/- 2.3 in the females and 22.6 +/- 1.0 mM in males. However, a significantly larger proportion of female 500-islet animals (6 of 16) achieved a plasma glucose level of 9.5 mM or less compared with males receiving 500 islets (2 of 30). Multivariate regression analysis suggests that sex and islet number interact to affect glycemic normalization after islet transplantation. Gender differences appear to influence body weight and plasma glucose responses to islet transplantation. This finding may have particular relevance when a marginal number of functional islets are available. PMID- 7988459 TI - Transformation of normal thyroids into colloid goiters in rats and mice by diphenylthiohydantoin. AB - Some years ago, we reported that colloid goiters could be produced experimentally in mice and rats by injection of TSH over a few days in the presence of ample iodine supply. This clearly showed that colloid accumulation and intense TSH stimulation are not mutually exclusive. In the present study, large colloid goiters, sharing many morphological and biochemical characteristics with human colloid goiters, were induced in rats and mice by treatment with 5,5-diphenyl-2 thiohydantoin (DPTH). This drug increases fecal loss of thyroid hormone and inhibits conversion of T4 to T3. Thus, DPTH raises TSH and induces macrofollicular colloid-rich goiters. In contrast to this, goiters induced by combined treatment with methimazole (MMI) or sodium perchlorate and DPTH are microfollicular, although serum TSH is increased to the same level as in rats treated with DPTH alone. The degree of iodine organification obviously determines if the follicle will sprout and form daughter follicles or if it will expand its hull. Thyroglobulin content of DPTH goiters is lower than that of normal glands but considerably higher than after MMI treatment, whereas total iodine content of DPTH goiters is only slightly lower than in normal glands, but also much higher than in MMI goiters. In DPTH goiters, a high proportion of total iodine is in the particulate fraction which probably contains the periodic acid Schiff-positive bodies floating in the colloid of DPTH treated glands. Acute DPTH administration does not inhibit iodide organification, but after treatment with DPTH for 1 day, chromatography suggests some inhibition of iodine organification and hormone synthesis by DPTH, but much less than by MMI. DPTH treatment causes considerable tissue damage and repair, such as follicular cell necrosis and invasion of the colloid by macrophages and granulation tissue. Therefore, DPTH goiters might well be a useful model not only for colloid goiter formation but also for inflammatory processes in the thyroid gland. PMID- 7988460 TI - Uptake of triiodothyroacetic acid and its effect on thyrotropin secretion in cultured anterior pituitary cells. AB - The uptake of [125I]triiodothyroacetic acid ([125I]Triac) in anterior pituitary cells was investigated and compared with that of [125I]T3. Furthermore, the effects of Triac, T3, and T4 on TSH release were compared. Cells isolated from adult male Wistar rats were cultured for 3 days in medium with 10% fetal calf serum. Uptake was measured at 37 C with [125I]Triac (100,000 cpm; 120 pM) or [125I]T3 (50,000 cpm; 50 pM) in medium with 0.5% BSA. In this medium, the ratio of the free fractions of Triac, T3, and T4 was 1:8:1. Exposure of cells to 100 nM TRH for 2 h stimulated TSH release by 80-110% (P < 0.001). Comparing total hormone levels (1 nM to 1 microM), Triac and T3 were equally effective in reducing this response, and both were 10-fold more effective than T4. The time course (15 min to 4 h) of [125I]Triac uptake was similar to that of [125I]T3, showing equilibrium after 1 h. Unlabeled Triac (1 microM) reduced the uptake of [125I]Triac and [125I]T3 at all time intervals. Expressed per pM free hormone, the cellular and nuclear uptake of [125I]Triac were twice those of [125I]T3. The 15-min uptake of [125I]Triac was reduced by incubation with 10 nM unlabeled Triac (35%; P < 0.001). Maximum inhibition (56%; P < 0.001) was found with 10 microM Triac. A similar effect was seen with 10 microM T3, T4, or 3,3',5,5' tetraiodothyroacetic acid. Preincubation (30 min) and incubation (15 min) with 10 microM oligomycin reduced the cellular ATP content by 51% (P < 0.001), [125I]T3 uptake by 77% (P < 0.001), and [125I]Triac uptake by only 25% (P < 0.001). The temperature dependence of [125I]Triac and [125I]T3 uptake was the same. Preincubation and incubation with 10 microM monensin (reduces the Na+ gradient) or 10 microM monodansylcadaverine (inhibits receptor-mediated endocytosis) reduced 15-min [125I] Triac uptake by 15% (P < 0.005) and 19% (P < 0.005), respectively. The data show that 1) Triac, on the basis of the free hormone concentration, is more potent than T3 or T4 in suppressing TSH secretion; and 2) the rapid uptake of [125I]Triac by the anterior pituitary occurs by a carrier mediated mechanism that is only partially dependent on ATP or the Na+ gradient. PMID- 7988461 TI - Regulation of rat insulin receptor tyrosine kinase by hypoglycemia. AB - To investigate the effect of hypoglycemia on the regulation of muscle-derived insulin receptor tyrosine kinase activity, four groups of Sprague-Dawley rats were studied: two groups in which either insulin (4 mU/kg.min) or phloridzin (3 mg/kg.min) was infused to acutely reach hypoglycemia (mean, 3.2-3.5 mM); and two control groups in which either saline or phloridzin (3 mg/kg.min) was infused, while maintaining euglycemia. Plasma glucose was maintained constant for 40 min in the hypoglycemic group and for 60 min in the phloridzin-infused euglycemic groups by a variable glucose infusion. Insulin receptors were isolated under conditions designed to preserve their in vivo phosphorylation state, and their tyrosine kinase activity toward poly(Glu-Tyr) was measured in the absence and presence of in vitro exposure to insulin. Insulin infusion resulted in an enhanced in vivo tyrosine kinase activity. Surprising was the finding of a slight increase of the in vivo tyrosine kinase activity in the phloridzin-infused hypoglycemic rats. The in vitro insulin dose-response curves of tyrosine kinase activity showed no significant differences between insulin-infused and control rats. In contrast, there was a marked increase of the insulin-stimulated kinase activity in phloridzin-infused hypoglycemic rats; at 100 nM insulin, tyrosine kinase activity was 1.8-fold more responsive when compared with either insulin infused rats or control groups. Moreover, in phloridzin-infused hypoglycemic rats, the half-maximal stimulation of tyrosine kinase activity was greater than 10-fold (0.36 +/- 0.01 nM) more sensitive to insulin than both insulin-infused (3.8 +/- 0.03 nM, mean +/- SE) and control groups (4.2 +/- 0.05 and 4.1 +/- 0.04 nM in saline- and phloridzin-infused euglycemic rats, respectively, mean +/- SE). In conclusion, hypoglycemia associated with low plasma insulin concentrations determines a hypersensitization of the intrinsic tyrosine kinase of the insulin receptor. PMID- 7988462 TI - Regulated endocrine-specific protein-18: a short-lived novel glucocorticoid regulated endocrine protein. AB - Regulated endocrine-specific protein-18 (RESP18) is an 18-kilodalton endocrine specific transcript whose expression is regulated by a number of different physiological and pharmacological stimuli in different tissues. RESP18 messenger RNA was identified in all cell types in the anterior pituitary, at levels that varied 2-fold from the lowest (corticotropes and thyrotropes) to the highest (gonadotropes, somatotropes, and mammotropes); the melanotropes of the intermediate pituitary have levels of RESP18 messenger RNA comparable to the highest levels in cells in the anterior pituitary. Mouse RESP18 was cloned and used as the basis for biosynthetic studies on RESP18 in AtT-20 cells, which express RESP18 endogenously; mouse RESP18 was highly homologous to rat RESP18. Pulse-chase biosynthetic labeling studies showed that AtT-20 cells expressed much less RESP18 than the endogenous prohormone, POMC, but that glucocorticoid treatment lowered POMC and raised RESP18 biosynthetic rates so that they were nearly equimolar. Surprisingly, RESP18 was not processed to smaller peptides to any significant extent, nor was RESP18 or any smaller peptide secreted. Newly synthesized RESP18 normally disappeared from AtT-20 cell extracts with a half life of less than 15 min; the intracellular half-life of RESP18 was increased strikingly after glucocorticoid treatment of the cells. Upon subcellular fractionation, RESP18 was found to be entirely particulate and to cofractionate with markers for the endoplasmic reticulum, rather than with markers for secretory granules, such as POMC and prohormone-processing enzymes. Therefore, RESP18 is a major glucocorticoid-responsive protein in the secretory pathway of corticotropes, but its function may be entirely within the neuroendocrine cell. PMID- 7988464 TI - Molecular cloning of the rat thyroxine-binding globulin gene and analysis of its promoter activity. AB - We cloned the rat T4-binding globulin (rTBG) gene, characterized its organization, and studied its promoter activity and regulation. A genomic DNA library was constructed and screened using an rTBG complementary DNA (cDNA) as a probe. An 8.6-kilobase pair (kbp) clone was partially sequenced and compared with the sequence of the previously cloned cDNA. It helped complete the cDNA sequence and identify the first noncoding exon (exon 0). The transcription start site was identified using an RNase protection assay. The rTBG genomic clone contained 1.2 kbp 5'-flanking and 1.7 kbp 3'-flanking regions. The sizes of exons and introns of the rTBG gene are similar to those of the human TBG gene, belonging to the serine protease inhibitor family. The 5'-flanking region contains a TATA box, a CAAT box, and a consensus sequence for the hepatocyte nuclear factor 1-binding site. We tested the promoter activity of the 1.2-kbp 5'-flanking region using a luciferase reporter plasmid. When transfected into a hepatocyte-derived cell line (HepG2), the plasmid construct containing the fragment -1227 to +11 (transcription start site, +1) showed a 9-fold increase in luciferase activity compared with that of a promoterless luciferase vector. No promoter activity was detected in a nonhepatocyte-derived cell line (COS1). Serial 5'-deletion revealed that the construct containing the fragment -180 to +11 had 40% of the maximal promoter-induced luciferase activity. And that containing the fragment -53 to +11 showed no significant increase of luciferase activity. These results suggest that the region -180 to -53, containing hepatocyte nuclear factor 1-binding site, is essential to the liver-specific expression. We previously reported down regulation of rTBG messenger RNA by T3 in vivo. The present study failed to show T3's effect on the promoter activity of the 1.2-kbp 5'-flanking region of the rTBG gene. PMID- 7988463 TI - Lipid hydroperoxides evoke antigonadotropic and antisteroidogenic activity in rat luteal cells. AB - At functional luteolysis, the rat corpus luteum generates hydrogen peroxide (H2O2), which is known to rapidly inhibit gonadotropin-sensitive cAMP and progesterone production in isolated luteal cells. Lipid peroxides also increase markedly in the rat corpus luteum with the onset of functional luteolysis, and H2O2 is a potent inducer of lipid peroxidation. However, the actions of lipid peroxides on cell function are unknown. The objective of this study was to investigate the impact of typical lipid peroxides, cumene hydroperoxide (CuOOH) and 15(S)-hydroperoxyeicosatetraenoic acid, on rat luteal cells. CuOOH inhibited both LH-sensitive cAMP accumulation (ED50, 25 microM) and progesterone production (ED50, 20 microM). 15(S)-hydroperoxyeicosatetraenoic acid also dose dependently inhibited steroidogenesis. A significant reduction of LH-stimulated progesterone production was evident within 5 min of treatment with CuOOH, whereas inhibition of cAMP accumulation was not evident until 60 min. 8-Bromo-cAMP and 22 hydroxycholesterol caused partial and complete reversal of CuOOH-inhibited progesterone secretion, respectively. Preincubation of cells with o phenanthroline completely reversed the inhibitory effects of CuOOH on cAMP accumulation and partially reversed its effects on progesterone production. Incorporation of radiolabeled amino acids into luteal proteins was significantly inhibited by CuOOH (25 microM) within 2 min of treatment and was reduced to 40 +/ 14% of control levels at 60 min. CuOOH (25 microM) maximally stimulated PGE2 production within 30 min of treatment (180 +/- 30% of control), a response that was completely blocked by aristolochic acid (100 microM), a phospholipase-A2 inhibitor, and indomethacin (1 microgram/ml), a prostaglandin (PG) synthesis inhibitor. The present results suggest that the acute inhibitory action of lipid peroxides on LH-stimulated progesterone production occurs down-stream of cAMP synthesis and appears to be due to impaired cholesterol utilization for steroidogenesis, possibly through inhibition of protein synthesis. The stimulation of PGE2 production by CuOOH appears to involve the activation of phospholipase-A2, which is a rate-limiting step in PG synthesis. Lipid peroxides as well as H2O2 may serve as mediators of functional luteolysis. PMID- 7988465 TI - Activation of the prolactin promoter in transfected GH3 cells by posterior pituitary cells. AB - We previously reported that PRL production is significantly enhanced by a PRL releasing/regulating factor derived from the posterior pituitary (PP). Specifically, the levels of PRL messenger RNA synthesis and release were dramatically increased in cocultures of GH3 and PP cells. The present objectives were to: 1) determine whether PP cells activate PRL gene transcription in a promoter- and cell-specific manner; 2) compare promoter activation by PP cells with that caused by selected substances that regulate the PRL gene; and 3) examine which region of the promoter (proximal and/or distal) mediates the action of the PP. In Exp 1, GH3 cells, transfected either with luciferase reporter plasmids containing a wild type PRL promoter, a GH promoter, or a glycoprotein alpha-subunit promoter, were cocultured with PP cells. Luciferase activity was used as an index for promoter activation. PP cells induced an 18-fold stimulation of the PRL promoter, as compared with a 2-fold stimulation of the GH promoter and no effect on the glycoprotein alpha-subunit promoter. In Exp 2, GH3 cells transfected with the wild type PRL promoter were cocultured with PP, anterior pituitary, uterine, or PC12 cells for 24 h. PP cells caused a 20-fold stimulation of the PRL promoter, whereas anterior pituitary cells showed a moderate 5-fold stimulation; uterine and PC12 cells caused minimal (< 2-fold) increases in luciferase activity. In Exp 3, GH3 cells were transfected with either the wild type PRL promoter (-2500 PRLluc) or with a truncated promoter (-425PRLluc) containing the proximal region only and were incubated with PP cells, TRH, vasoactive intestinal peptide (VIP), epidermal growth factor (EGF), or estradiol (E2) for 24 h. Compared with the induction of the wild type promoter, PP cells activated the truncated promoter by 30% only. Stimulation of the promoter by relatively high concentrations of TRH, VIP, EGF, or E2, either alone or in combination, was significantly less effective than that caused by PP cells. CONCLUSIONS: 1) PP cells stimulate PRL gene transcription in a tissue- and promoter-specific manner; 2) the magnitude of induction caused by PP cells far exceeds that caused by high concentrations of TRH, VIP, EGF, or E2; and 3) the distal enhancer region of the rat PRL gene is necessary for maximal responsiveness of the PRL promoter to PP cells. PMID- 7988466 TI - Peptide V: a VGF-derived neuropeptide purified from bovine posterior pituitary. AB - The objective of this study was to purify PRL-releasing factor (PRF) from the bovine posterior pituitary (PP) and determine its structure. Five hundred bovine PPs were acid extracted and fractionated using gel filtration chromatography followed by semipreparative and analytical HPLC. PRF activity was determined by an in vitro bioassay. After six chromatographic steps, a single peak with PRF activity was resolved. As determined by mass spectrometry and microsequencing, this peak contained a major peptide composed of 30 amino acids with a mol wt of 3708K. A synthetic peptide was then produced by solid-phase synthesis. When tested both in vivo and in vitro, the synthetic peptide lacked PRF activity. Further HPLC fractionation under different conditions resolved the synthetic peptide from a highly purified PRF activity. This indicated that the isolated peptide was coincidentally eluted with PRF during the purification. The major isolated peptide has 94% identity with a sequence at the C-terminus of a rat protein named VGF. VGF is a nerve growth factor-inducible protein that has been identified in PC12 cells and is localized in selected sites throughout the central nervous system. The isolated peptide has an Arg-Arg cleavage site at its junction within the VGF protein. Based on this information, we named this substance Peptide V (VGF-derived peptide). We postulate that Peptide V is: 1) a natural cleavage product of the VGF protein; 2) produced and processed either in the hypothalamus or within the pituitary proper, and 3) a releasable peptide that fulfills one or more endocrine functions. PMID- 7988467 TI - Pituitary adenylate cyclase-activating polypeptide stimulates both adrenocortical cells and chromaffin cells in the frog adrenal gland. AB - In a previous report, we have shown that frog pituitary adenylate cyclase activating polypeptide (fPACAP38) is a potent stimulator of corticosteroid secretion by frog adrenal slices in vitro. The aim of the present study was to determine the mode of action of PACAP on the frog adrenal gland. Immunoelectron microscopic labeling revealed that PACAP-like immunoreactivity is present in electron-dense vesicles within nerve endings located in the vicinity of both adrenocortical and chromaffin cells. Exposure of dispersed adrenal cells to fPACAP38 caused stimulation of corticosteroid secretion. Labeling of cultured adrenal cells with [125I]PACAP27 revealed the existence of PACAP-binding sites on both adrenocortical and chromaffin cells. Saturation and competition experiments showed the occurrence of high affinity and selective receptors for fPACAP38 on cultured adrenal cells. fPACAP38 (10(-8)-10(-5) M) provoked a dose-dependent stimulation of cAMP production by frog adrenal slices. Microflurimetric studies demonstrated that fPACAP38 induced a substantial elevation of the intracellular calcium concentration in both adrenocortical and chromaffin cells. The present results indicate that in the frog adrenal gland, PACAP fibers innervate both adrenocortical and chromaffin cells. The data show the presence of PACAP receptors on the two cell types. PACAP exerts a direct stimulatory effect on corticosteroid-producing cells. This effect is probably mediated through stimulation of adenylyl cyclase activity and/or augmentation of intracellular Ca2+. PACAP also increases intracellular Ca2+ in chromaffin cells. These data suggest that PACAP, released locally in the adrenal gland, acts as a neuroendocrine factor, regulating the activity of adrenocortical and chromaffin cells. PMID- 7988468 TI - Visualization of gamma-aminobutyric acid A receptors on proopiomelanocortin producing neurons in the rat hypothalamus. AB - It has recently been shown that gamma-aminobutyric acid (GABA) and central-type benzodiazepine receptor agonists inhibit the expression of the POMC gene and the release of POMC-derived peptides from hypothalamic neurons. To determine whether the inhibitory effect of GABA could be accounted for by a direct action on POMC neurons, we investigated the localization of the beta 1-subunit of the GABAA benzodiazepine-receptor complex in the arcuate nucleus. Using a monoclonal antibody raised against a synthetic fragment of the beta 1-subunit, we demonstrate the presence of GABAA receptor on POMC neurons. The proportion of POMC neurons that exhibit immunoreactivity for the beta 1-subunit of the GABAA receptor was not significantly different in the posterior portion (73.0-76.0%) and anterior portion (61.3-62.7%) of the arcuate nucleus. The data also revealed that in the arcuate nucleus, a majority of neurons that were immunostained by the antibody to the beta 1-subunit were not POMC positive. The present results support the concept that GABAA and central-type benzodiazepine receptor agonists exert a direct inhibitory action on POMC neurons. The data also indicate the existence of subsets of POMC neurons within the arcuate nucleus. PMID- 7988469 TI - Growth hormone induces expression of the c-fos gene on hypothalamic neuropeptide Y and somatostatin neurons in hypophysectomized rats. AB - The neuronal expression of the protooncogene c-fos may serve as a marker of neural activity. We previously examined brain sites upon which GH exerts an immediate early influence in rats and determined that the c-fos gene was transiently expressed in the hypothalamic periventricular nucleus (PeV) and arcuate nucleus (ARC) after recombinant human GH (rhGH) administration. As the distribution of c-fos messenger RNA (mRNA)-containing cells appeared to overlap with that of somatostatin (SS) neurons in both the PeV and ARC, we hypothesized that GH exerts a feedback effect on hypothalamic SS neurons. To extend this hypothesis, we characterized the neurons expressing the c-fos gene in response to rhGH administration in hypophysectomized rats. Adult male Wistar rats were hypophysectomized 10 days before use. After hypophysectomy, rats received daily sc injections of cortisone acetate (0.5 mg/kg BW) and L-T4 (20 micrograms/kg BW). Four international units (1.33 mg) of rhGH were given iv through an indwelling right atrial cannula. The vehicle was given to the control animals. Coronal sections of the hypothalamus were processed for in situ hybridization after rhGH or vehicle administration. To estimate the localization of neurons expressing the c-fos gene, the adjacent hypothalamic sections, 30 microns in thickness, were processed for hybridization histochemistry for SS, neuropeptide-Y (NPY), or GRF mRNA. In the ARC, the distribution of c-fos mRNA-containing cells appeared to overlap with that of NPY and partially with that of SS mRNA-containing cells, but it clearly differed from the distribution of GRF mRNA-containing cells. In the PeV, distribution of the cells expressing the c-fos gene was comparable to that of SS mRNA-containing cells. To further ascertain the distribution, hypothalamic sections, 6 microns in thickness, were processed by double label in situ hybridization using a 35S-labeled c-fos cRNA probe and a digoxigenin-labeled NPY or SS cRNA probe. In the ARC, 65% of the c-fos gene-expressing cells were NPY neurons. In the PeV, 60% of the c-fos gene-expressing cells were SS neurons. NPY is known to act within the hypothalamus and inhibit GH secretion via SS in rats, and the NPY neurons in the ARC have been shown to project to SS neurons in the PeV. Our findings suggest that the feedback effect of GH on the hypothalamus is mediated not only by SS neurons in the PeV, but also by NPY neurons in the ARC. PMID- 7988470 TI - Novel regulation of pregnant human myometrial smooth muscle cell gap junctions by human chorionic gonadotropin. AB - Human myometrium contains hCG/LH receptors. There are fewer of these receptors during labor compared to no labor at preterm or term deliveries. Exogenous hCG can directly inhibit oxytocin-stimulated human myometrial contractions. These findings suggest that hCG may directly maintain myometrial quiescence during pregnancy. As maintenance of uterine quiescence may involve down-regulation of myometrial gap junctions, we investigated the effect of hCG on connexin-43 (CX 43) gene expression from RNA to protein and morphological gap junctions. The addition of 5 or 10 nM highly purified hCG to subconfluent cultures of pregnant myometrial smooth muscle cells resulted in a significant decrease in CX-43 protein levels. Higher hCG concentrations (100 and 1000 nM), however, had no effect. The maximal effect of hCG was seen at 4-8 h of culture, followed by recovery after a longer duration of culture. hCG treatment also concomitantly decreased CX-43 messenger RNA and morphological gap junctions. The hCG effect on CX-43 protein levels is hormone specific and mediated by protein kinase-A signaling. Estradiol and oxytocin increased, whereas progesterone decreased, CX 43 protein levels and morphological gap junctions. The oxytocin-induced increase was reversed by cotreatment with hCG. Although RU 486 alone had no effect on CX 43 protein levels, it prevented the down-regulating action of hCG and progesterone. In summary, our results demonstrate that hCG can directly decrease CX-43 messenger RNA, protein, and morphological gap junctions in cultured pregnant human myometrial smooth muscle cells. The hCG action is concentration and time dependent, hormone specific, and mediated by protein kinase-A signaling and appears to involve progesterone receptors. These data lend support to the concept that hCG could be one of the hormones responsible for maintaining uterine quiescence by down-regulating myometrial gap junctions during pregnancy. PMID- 7988471 TI - Mouse endometrial tumor necrosis factor-alpha messenger ribonucleic acid and protein: localization and regulation by estradiol and progesterone. AB - Tumor necrosis factor-alpha (TNF) messenger RNA (mRNA) and protein have been identified in the uteri of cycling rats, mice, and women. In this study, a mouse model was used to investigate the cell-specific expression and regulation of the TNF gene in the endometrium. Uteri from cycling and ovariectomized hormone reconstituted mice were tested by in situ and Northern blot hybridizations as well as by immunohistochemistry. Cyclic variations were observed in TNF mRNA. Although weak to undetectable during proestrus, estrus, and diestrus-I, TNF mRNA was present in both epithelial and stromal cells on diestrus-II. TNF protein was observed in the endometrium on each day of the estrous cycle, primarily in the epithelial cells. Stromal TNF immunoreactivity was observed only during diestrus I. Seven days after ovariectomy, TNF mRNA and protein were undetectable in the endometrium. Specific message and protein were restored in both epithelial and stromal cells after administration of 17 beta-estradiol (E2), progesterone (P4), and E2 plus P4. E2 treatment resulted in a biphasic pattern of TNF mRNA expression. mRNA was present in epithelial cells 1 and 6 h posttreatment, was not detectable after 24 h, and then was present in both the epithelium and stroma after 72 h. In contrast, TNF mRNA was detectable at all time points after P4 administration. TNF mRNA was localized to both the epithelium and stroma until 72 h of P4 treatment, when stromal TNF mRNA was no longer detectable. TNF mRNA was also present at all time points examined after the combination E2 and P4 treatment. TNF mRNA was invariably localized to the epithelium; however, stromal mRNA fluctuated over the course of treatment. TNF mRNA was in the stroma 1 and 24 h post-E2 plus P4 treatment, but was not present at the 6 and 72 h points. In general, the pattern of TNF protein matched that of the TNF mRNA, with a few exceptions. Twenty-four hours after E2 treatment, TNF mRNA was not detectable; however, TNF protein was present in the epithelium. The opposite was observed 24 h after E2 plus P4 administration when the epithelium and stroma contained TNF mRNA; however, no protein was observed. In addition, with the exception of 72 h of E2 treatment, stromal TNF protein was not abundant, although TNF mRNA was often detected. In summary, the results of this study indicate that both epithelial and stromal cells contain TNF mRNA and protein and that E2 and P4 exert individual influences on the cell-specific expression of TNF transcripts and protein. PMID- 7988472 TI - Induction of growth plate cartilage ossification by basic fibroblast growth factor. AB - In mammals, longitudinal bone growth results from the precise coupling of chondrogenesis and osteogenesis within the epiphyseal growth plate, a process termed endochondral ossification. The mechanisms coupling chondrogenesis and osteogenesis are unknown. Previous studies have shown that both basic fibroblast growth factor (bFGF) and acidic FGF are expressed by growth plate chondrocytes. Here we show that bFGF, infused directly into the rabbit proximal tibial growth plate, accelerates vascular invasion and ossification of growth plate cartilage. Our results suggest the possibility that bFGF (or a related member of the FGF family) couples osteogenesis to chondrogenesis by attracting vascular and bone cell invasion from the adjacent metaphyseal bone. PMID- 7988473 TI - C-type natriuretic peptide (CNP) in the pituitary: is CNP an autocrine regulator of gonadotropes? AB - Natriuretic peptides act via receptors with intrinsic guanylate cyclase activity to stimulate cGMP production and are thought to be important regulators of neuroendocrine systems. C-Type natriuretic peptide (CNP) is of particular interest in this regard because the highest tissue concentrations of CNP occur in the anterior pituitary, where it is a highly potent stimulator of cGMP production. Here we show that pituitaries of rats and mice contain abundant CNP prohormone messenger RNA (mRNA), but no atrial natriuretic peptide or B-type natriuretic peptide prohormone mRNAs. Using reverse transcriptase-polymerase chain reaction, both A- and B-type natriuretic peptide receptor (GC-A and GC-B, respectively) transcripts were detected in rat and mouse pituitaries, although only the GC-B mRNA was measurable by Northern blotting. Immunohistochemistry revealed CNP-positive cells in the anterior, but not posterior, pituitaries of rats, and the vast majority of these cells were identified as gonadotropes by colocalization of CNP and LH immunoreactivities. Targeted toxicity using GnRH conjugated to the ricin-A chain was used to test whether gonadotropes are also direct targets for GnRH action. The conjugate dose dependently inhibited the proliferation of alpha T3-1 cells (gonadotrope-derived cells with GnRH receptors), but had no such effect on GH3 cells (which do not have GnRH receptors). Culture of rat pituitary cells with the conjugate caused comparable reductions in CNP-stimulated cGMP production, GnRH-stimulated LH release, and CA2+ ionophore (A23187)-stimulated LH release, but did not measurably alter cAMP production in response to pituitary adenylate cyclase-activating polypeptide. We conclude that CNP is synthesized in the pituitary, where it is located predominantly in gonadotropes, and GC-B receptors expressed in the pituitary mediate the direct effects of CNP in gonadotropes. Together with the recent demonstration of CNP synthesis and action in alpha T3-1 cells, the data suggest CNP to be a novel autocrine regulator of gonadotropes. PMID- 7988474 TI - Mouse growth hormone-binding protein and growth hormone receptor transcripts are produced from a single gene by alternative splicing. AB - Serum contains a soluble growth hormone-binding protein which is produced in some species by proteolytic cleavage of the extracellular domain of the growth hormone receptor. The hypothesis that a growth hormone-binding protein messenger RNA is produced in other species by alternative splicing of nascent growth hormone receptor transcripts was confirmed by analysis of the mouse growth hormone receptor gene. An exon that encodes the hydrophilic tail of the binding protein is located between an exon encoding the final portion of the hormone binding domain and an exon encoding the hydrophobic transmembrane domain of the receptor. PMID- 7988475 TI - A peptide related to gastrin releasing peptide is synthesised and secreted by the ovine endometrium in early pregnancy. AB - We have previously shown that the peptide immunoreactivity related closely to the mitogen GRP is expressed by the pregnant ovine endometrium during the final third of pregnancy. In this study we have established that GRP is also expressed early in ovine pregnancy and have quantified the temporal changes in synthesis, storage and secretion of GRP in the peri- and post-attachment period. Secreted GRP peptide levels rise 10 fold just prior to implantation, while endometrial peptide and mRNA concentrations increase 4 and 13 fold respectively between day 17 and 20, immediately following attachment and corresponding to the onset of placentome development. The main molecular form of endometrial GRP has similar binding characteristics on RP-HPLC to GRP 18-27, but is larger. We conclude that a GRP like peptide is expressed by the pregnant ovine endometrium from early in pregnancy until term, and that it is likely to play an important role in fetal or uterine maturation. PMID- 7988476 TI - Subtype selectivity of peptide analogs for all five cloned human somatostatin receptors (hsstr 1-5). AB - Recent reports (Raynor et al) have claimed the identification of potent somatostatin (SST) agonists exhibiting binding affinities of 1-2 pM and up to 30,000 fold binding selectivity for several of the 5 cloned sstr subtypes. These conclusions, however, are based on binding comparisons of sstr subtypes from different species expressed in different cell lines and studied with different radioligands. To eliminate the effect of species and/or methodological variations, we have investigated agonist selectivity of 32 synthetic SST analogs for all 5 hsstrs stably expressed in CHO-K1 cells under identical binding conditions. We show that hsstr2, 3, 5 react potently with hexapeptide as well as cyclic and linear octapeptide analogs and belong to a similar sstr subclass. hsstr1 and 4 react poorly with these analogs and belong to a separate subclass. The present generation of SST analogs exhibit a modest-50 fold increase in binding potency compared to SST-14 for 2 subtypes (hsstr2, 3), and relative selectivity for only 1 subtype (hsstr2) which is at best only 35 fold. The potency and degree of selectivity of these analogs is several orders of magnitude less than that reported earlier and suggests the need for caution in using these compounds as putative superagonists or subtype selective compounds for any of the individual sstrs. PMID- 7988477 TI - 1,25-Dihydroxy-24-OXO-16ene-vitamin D3, a renal metabolite of the vitamin D analog 1,25-dihydroxy-16ene-vitamin D3, exerts immunosuppressive activity equal to its parent without causing hypercalcemia in vivo. AB - The hormone, 1,25-(OH)2D3, is metabolized into 1,25-(OH)2-24-OXO-D3, in kidney prior to conversion to its final inactive product, calcitroic acid. Similarly, 1,25-(OH)2-24OXO-16eneD3, is produced in the kidney from the Vitamin D analog, 1,25-(OH)2-16eneD3, but resists further hydroxylation. The analog's metabolite was synthesized and its biologic activity compared to the parent compound. Naive SJL/J mice, 4 weeks old, were immunized with neuroantigen in adjuvant to induce experimental autoimmune encephalomyelitis [EAE]. Treatment with 1,25-(OH)2-24OXO 16eneD3 was given at 0.05, 0.15 and 0.3 microgram I.P., on alternate days, starting 3 days prior and for up to 5 days post immunization and compared to a similar treatment with 0.1 microgram 1,25-(OH)2D3 or 1,25-(OH)2-16eneD3. Suppression of EAE was observed with 0.15 microgram 1,25-(OH)2-24OXO-16eneD3, comparable to the suppression induced with the parent compound and more potent than 1,25-(OH)2D3. However, no hypercalcemia was seen in mice treated with 0.15 microgram of OXO-metabolite (9.7 +/- 0.6 vs 9.3 +/- 1.1 mg/dl, treated vs controls), in contrast to 1,25-(OH)2D3 and 1,25-(OH)2-16eneD3 (11.2 +/- 1.0 and 11.0 +/- 0.9 mg/dl respectively; p < 0.001). In summary, our results suggest that 1,25-(OH)2-24OXO-16eneD3, a stable intermediary metabolite of the vitamin D analog, 1,25-(OH)2-16eneD3 exerts immunosuppressive activity equal to its parent without causing hypercalcemia in vivo. PMID- 7988478 TI - 1,25-Dihydroxyvitamin D3 increases the cellular content of the calcium-activated neutral protease mu-calpain in renal cell carcinoma. AB - mu-Calpain is a calcium-dependent neutral thiol protease activated by micromolar concentrations of calcium. mu-Calpain is implicated in various cellular functions regulated by calcium including exocytosis, cell fusion, apoptosis and control of cell proliferation. We studied the effect of 1,25-(OH)2D3 on mu-calpain levels in the human renal cell carcinoma line SK-RC-29 using monoclonal antibodies to the 80 kDa subunit of mu-calpain. Exposure of low density cultures (15000 cells/cm2) to 1,25-(OH)2D3 (100nM) for 48 hours resulted in 1.5-3 fold increase of mu calpain cell content. The effect was not observed in higher density cultures (40000 cells/cm2). mu-Calpain content of high density cultures was higher than that of low density cultures and similar to that in low density cultures treated by 1,25-(OH)2D3. The cellular content of two other calcium binding proteins, annexin II and annexin VI was not affected by the hormone. 1,25-(OH)2D3 did not affect cell number or viability therefore its effect on mu-calpain is not secondary to changes in cell density. The effect of 1,25-(OH)2D3 was dose dependent apparent already at 1nM and was not observed with 24,25-(OH)2D3. Increase in mu-calpain content may underlie some of the actions of 1,25-(OH)2D3 on classical and non classical target cells. PMID- 7988479 TI - Hormonal regulation of human corticotropin-releasing hormone gene expression: implications for the stress response and immune/inflammatory reaction. PMID- 7988480 TI - Disorders of steroid 11 beta-hydroxylase isozymes. AB - The most active corticosteroids are 11 beta-hydroxylated. Humans have two isozymes with 11 beta-hydroxylase activity that are respectively required for cortisol and aldosterone synthesis. CYP11B1 (11 beta-hydroxylase) is expressed at high levels and is regulated by ACTH, whereas CYP11B2 (aldosterone synthase) is normally expressed at low levels and is regulated by angiotensin II. In addition to 11 beta-hydroxylase activity, the latter enzyme has 18-hydroxylase and 18 oxidase activities and thus can synthesize aldosterone from deoxycorticosterone. Insights into the normal functioning of these enzymes are gained from studies of disorders involving them. Mutations in the CYP11B1 gene cause steroid 11 beta hydroxylase deficiency, a form of congenital adrenal hyperplasia characterized by signs of androgen excess and by hypertension. Mutations in CYP11B2 result in aldosterone synthase (corticosterone methyloxidase) deficiency, an isolated defect in aldosterone biosynthesis that can cause hyponatremia, hyperkalemia, and hypovolemic shock in infancy and failure to thrive in childhood. These are both recessive disorders. Unequal crossing over between the CYP11B genes can generate a duplicated chimeric gene with the transcriptional regulatory region of CYP11B1 but sufficient coding sequences from CYP11B2 so that the encoded enzyme has aldosterone synthase (i.e. 18-oxidase) activity. This results in aldosterone biosynthesis being regulated by ACTH, a condition termed glucocorticoid suppressible hyperaldosteronism. This form of genetic hypertension is inherited in an autosomal dominant manner. PMID- 7988481 TI - Hypophosphatasia and the role of alkaline phosphatase in skeletal mineralization. PMID- 7988482 TI - Gonadotropin-releasing hormone receptors: structure and signal transduction pathways. PMID- 7988483 TI - Medical therapy for differentiated thyroid carcinoma. AB - While some of the studies with new therapeutic modalities are encouraging, all are in their early experimental phases. It is likely that better understanding of the molecular basis for differentiated thyroid carcinoma will lead to new therapy in the next decade. PMID- 7988484 TI - Insulin-dependent diabetes mellitus as an autoimmune disease. AB - IDDM is unquestionably an autoimmune disease, as reflected by the presence of beta-cell-reactive autoantibodies and T cells, T cell-mediated transfer of the disease in nondiabetic mice, rats, and humans, and disease sensitivity to immunosuppressive therapy. T cells are predominantly, if not exclusively, involved in creating the islet lesions that lead to beta-cell atrophy after a stage of reversible inflammation. A full understanding of the disease pathogenesis will require a better definition of the nature of the triggering and target autoantigen(s) and of the effector mechanisms (cytokines, cytotoxic cells?). Much less information is available on the etiology than on the pathogenesis. Genetic factors are mandatory and the involvement of predisposition genes (HLA and non-HLA) is now being unravelled. The modulatory role of environmental factors is demonstrated by the high disease discordance rate in identical twins and by experimental data showing positive and negative modulation of the disease by a number of agents, notably infectious agents and food constituents. It is not clear, however, whether a given environmental factor, e.g. a precise virus or a cow's milk component, plays a real etiological role in a selected genetic background. IDDM thus appears as a multifactorial disease. It is not known, however, whether all factors intervene concomitantly in a given individual or separately in subsets of patients, explaining the clinical heterogeneity of the disease. The mechanisms underlying the loss of tolerance to self beta-cell autoantigen(s) are still unknown. Defective intrathymic negative selection of autoantigen-specific autoreactive T cell clones is unlikely. Breakdown of T cell anergy could occur according to various mechanisms, including aberrant expression of MHC molecules and molecular mimicry. Defective suppressor T cell function, perhaps related to TH1/TH2 imbalance, probably intervenes by amplifying the anti-beta-cell autoimmune response whatever its triggering mechanism. Before putative etiological agents are identified, one must base immunotherapy on nonantigen-specific agents. Results recently obtained in NOD mice indicate that the goal of nontoxic long-lasting immune protection from the disease is feasible if treatment is started early enough. In some cases (anti-T cell monoclonal antibodies), it appears that specific unresponsiveness can be induced. This double strategy (early intervention, tolerance induction) is the main challenge for immunodiabetologists.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 7988486 TI - Citation for the Edwin B. Astwood Lecture Award of the Endocrine Society to Patricia K. Donahoe. PMID- 7988485 TI - Citation for the Fred Conrad Koch Award of the Endocrine Society to Susan E. Leeman. PMID- 7988487 TI - Citation for the Rhone-Poulenc Rorer Clinical Investigation Lecture Award of the Endocrine Society to Samuel Refetoff. PMID- 7988488 TI - Citation for the Sidney H. Ingbar Distinguished Service Award of the Endocrine Society to Nicholas C. Ling, Maurice Manning, and Jean Rivier. PMID- 7988489 TI - Citation for the Gerald D. Aurbach Lecture Award of the Endocrine Society to Henry Morris Kronenberg. PMID- 7988490 TI - Citation for the Robert H. Williams Distinguished Leadership Award of the Endocrine Society to Robert M. Blizzard. PMID- 7988491 TI - Citation for the Ernst Oppenheimer Award of the Endocrine Society to Kelly E. Mayo. PMID- 7988492 TI - Citation for the Richard E. Weitzman Memorial Award to Fredric E. Wondisford. PMID- 7988493 TI - Nicotine effects on neutrophil F-actin formation and calcium release: implications for tobacco use and pulmonary diseases. AB - Alterations in neutrophil functions by tobacco components may play a pivotal role in pulmonary emphysema. This study examined the role of nicotine in altering F actin formation and calcium (Ca2+) release (two early events in neutrophil motility). The effects of these alterations on the motile function of phagocytosis were also examined. Human peripheral neutrophils from medically healthy nonsmoking subjects were incubated with nicotine at concentrations normally encountered during acute exposure to cigarette smoke (10(-2) to 10(-5) M) and/or the chemotactic peptide FLPEP (10(-7) M). Relative F-actin stain was determined by NBD phallacidin staining followed by flow cytometry. Intracellular Ca2+ was determined by INDO-1 AM loading followed by emission ratio quantitation by fluorometry. Phagocytosis was determined by the % phagocytic cells with carboxylated microspheres. Incubation of neutrophils with varying concentrations of nicotine resulted in a significant elevation of the relative F-actin stain at 30 s at 10(-2) and 10(-3) M (p < .05, ANOVA) and at 30 min at 10(-2) to 10(-4) M (p < 0.05). In time course studies with 10(-7) M FLPEP stimulation, there was a approximately 325% rise in relative F-actin stain at 30-60 s, followed by a gradual decrease to near baseline levels. There was an immediate rise in Ca2+ to approximately 150% over baseline values, followed by a gradual decrease to baseline. By contrast, stimulation with nicotine demonstrated a approximately 105% increase in relative F-actin staining at 10(-2) M (p < .001, ANOVA) and a smaller increase at 10(-3) M, which remained elevated up to 600 s. Intracellular Ca2+ levels also rose in a dose-dependent manner with an increased of 700% over baseline with 10(-2) M nicotine, and remained elevated up to 600 s. Coincubation with both FLPEP and nicotine demonstrated additive effects in relative F-actin staining at both maximal and submaximal concentrations. Preincubation with 10(-2) or 10(-3) M nicotine suppressed the % phagocytic cells by 32% and 16%, respectively (p < .001, ANOVA) with only a 1-4% reduction in cell viability (trypan blue exclusion). The results demonstrate that the concentration of nicotine during acute cigarette exposure can directly stimulate neutrophil F actin formation and intracellular Ca2+ release by a mechanism different from peptide stimulation. The alteration of these two pivotal neutrophil signaling events by nicotine may in turn alter other neutrophil functions in tobacco related pulmonary emphysema. PMID- 7988494 TI - Use of anti-TNF-alpha antiserum to investigate toxic alveolitis arising from cotton dust exposure. AB - Cotton dust has been associated with byssinosis and toxic alveolitis. A murine animal model has been developed with which to investigate the pathogenesis of these disorders. Studies with the model have reproduced the neutrophilic inflammation characteristic of the alveolitis, and have shown the presence of tumor necrosis factor-alpha (TNF-alpha) in the bronchoalveolar lavage (BAL) fluid. The current study investigated the role of TNF-alpha in the inflammatory response by use of a polyclonal antiserum to recombinant murine TNF-alpha. Following a 4-h exposure to cotton dust, experimental animals showed a 40-fold increase in BAL cells with 92% neutrophils. There was a 24-fold increase in TNF alpha in the BAL fluid. Up regulation of TNF-alpha mRNA expression was detected in BAL cells. Mice pretreated with anti-TNA-alpha antiserum displayed a marked attenuation of the neutrophilic inflammation; however, the level of TNF-alpha mRNA expression was not reduced in these mice. These studies support a major role of TNF-alpha in the toxic alveolitis induced by cotton dust inhalation. PMID- 7988495 TI - Alveolar macrophage inhibition of lung-associated NK activity: involvement of prostaglandins and transforming growth factor-beta 1. AB - Natural killer (NK) activity plays an important role in host defense. It is likely that this defensive role is shaped by compartmental and local environmental factors. The present study investigated the regulatory effects of alveolar macrophages (AM) on lung-associated NK activity. AM and lung lymphocytes (LL) were permitted to interact in a two-chamber system which prohibited cell contact but supported diffusion of soluble factors. AM were found to inhibit NK activity from LL in a time-dependent and reversible manner. The inhibitory event was shown to be mediated by soluble factors acting upon a post-binding event(s) in the lytic pathway of LL. AM inhibition was sensitive to indomethacin treatment (10(-5) M), which caused a decrease in prostaglandin E2 (PGE2) concentrations. Quantitation of PGE2 levels and treatment of LL with exogenous PGE2 indicated that the inhibitory effect could not be exclusively due to PGE2. It was subsequently found that exogenous transforming growth factor-beta 1 (TGF-beta 1) also inhibited LL NK activity and that treatment of inhibitory AM supernatant with a neutralizing antibody to TGF-beta 1 adsorbs up to 55% of its inhibitory activity. Moreover, the amount of TGF-beta 1 found in AM-LL co-culture media (25 pg/mL) correlated well with the level of NK inhibition observed. By contrast, platelet-derived growth factor and nitric oxide did not play a significant role in mediating AM suppression. Taken together, the data suggest that AM inhibit lung NK activity by interfering with post-binding lytic event(s) through the production of PGE2 and TGF-beta 1. PMID- 7988497 TI - Distribution of lysozyme and mucin (MUC2 and MUC3) mRNA in human bronchus. AB - Immunocytochemical studies have shown that gel-forming glycoproteins (mucins) and the bacteriolytic protein lysozyme are selectively expressed in airway mucous and serous cells, respectively. The mechanisms mediating this selectivity are unknown. In this study, we localized mucin and lysozyme mRNA by in situ hybridization to investigate the possibility that phenotype-specific expression of these proteins is controlled at the level of mRNA. Radiolabelled sense and antisense probes were constructed from the human tracheal mucin cDNA, HAM1 (MUC2 gene), the human small intestinal mucin cDNA, SIB139 (MUC3 gene), and the bovine tracheal lysozyme cDNA, Lys 7a. Frozen sections of human bronchus were hybridized with these probes and washed under routine conditions. Autoradiography showed that although lysozyme mRNA was strictly limited to cells expressing lysozyme, mucin mRNA was present both in mucin-expressing and mucin-non-expressing epithelial cells. This suggests that the restriction of lysozyme to serous cells is controlled at the level of mRNA (synthesis and/or degradation), whereas the restriction of mucin to mucous cells is controlled at the level of translation. PMID- 7988496 TI - Effects of the beige mutation on respiratory tract infection with Pseudomonas aeruginosa in mice. AB - The role of neutrophil proteinases in the pathogenesis of respiratory tract infections with Pseudomonas aeruginosa was evaluated by studying the course of murine respiratory tract infection with a clinical isolate of P. aeruginosa mucoid strain developed by the agarose beads method in C57BL/6J(bg/bg) mice (beige mice). Neutrophils of beige mice are known to have defects in elastase and cathepsin G, but to have normal ability to produce reactive oxygen species. Contrary to the reported high susceptibility of beige mice to bacterial infections, we found that intratracheal inoculation of approximately 10(5) colony forming units (CFU) of P. aeruginosa enmeshed in agarose beads resulted in lower mortality (0/16 versus 16/16, p < .01), fewer CFU counts in the lungs on day 5 (p < .05), and fewer elastolytic lung tissue injuries in beige mice compared with C57BL/6(+/+) mice. In vitro bactericidal study, however, revealed that beige neutrophils killed fewer bacteria than those of C57BL/6(+/+) mice (p < .05). Neutrophil elastase activities in the supernatants of pulmonary lavaged fluids measured using methoxysuccinyl-alanyl-alanyl-prolyl-valine-4-methylcoumar-7-amide were lower (p < .05) in beige mice than those in the normal littermates, whereas neutrophil recruitment into the airways and production of superoxide anion measured as the superoxide dismutase inhibitable rate of cytochrome c reduction were not impaired. These results suggest that neutrophil proteinases play a key role in tissue injuries in the respiratory tract infection with P. aeruginosa. PMID- 7988498 TI - Seizures with onset in the sensorimotor face area: clinical patterns and results of surgical treatment in 20 patients. AB - It is not generally appreciated that intractable seizures involving the face area are amenable to surgical treatment. Twenty patients with onset of sensorimotor seizures in the face area of the pre- and postcentral gyri have been studied and surgically treated since 1948. Seizures started in the face, tongue, or throat, followed by diverse patterns depending on spread of seizure activity. Two patients had epilepsia partialis continua; 6 had either tonic or atonic drop attacks. All patients had pre- and postcentral face area resections, 12 in the dominant hemisphere. In addition, 3 had more extensive postcentral removal, 7 had temporal lobe, and 4 had small separate or contiguous frontal or parietal resection. Because the seizures were not sufficiently reduced by the first operation, 6 required reoperation; 4 of these patients had residual epileptiform activity on electrocorticogram (ECoG) after the first resection. Three patients had new neurologic signs that did not return to the preoperative level, but in 2 of them the deficit related mainly to higher resection in the central area. All but 2 of these 20 patients had at least moderate seizure reduction. Corticectomy can be performed for treatment of seizures arising in the lower central area and usually does not lead to significant permanent neurologic deficit. PMID- 7988499 TI - Benign rolandic epilepsy: high central and low central subgroups. AB - The spikes in benign rolandic epilepsy (BRE) typically involve both the central and midtemporal regions as recorded on standard EEG montages, but the seizures are characterized by sensorimotor manifestations that are rarely referrable to the temporal lobe. To study this apparent disparity, we evaluated the field distribution of interictal spikes in 33 BRE patients using closely spaced electrodes (AEEGS 1990) arranged over perisylvian cortex. None of the 33 patients showed maximum negativity in the midtemporal regions (T3/T4). Instead, maximum negativity was evident in the high central region (C3/C4) in 10 children (30.3%) and in the low central region (C5/C6) in 23 (69.7%). Hand involvement was significantly frequent (50%) in the high central group, and drooling with oromotor involvement was a distinctive symptom (65.2%) in the low central group. Our findings indicate that the spikes in patients with BRE are exclusively suprasylvian in origin and correlate with two electroclinical subgroups. PMID- 7988500 TI - Low-grade glial neoplasms and intractable partial epilepsy: efficacy of surgical treatment. AB - We performed a retrospective study of 51 consecutive patients who underwent operation for intractable partial epilepsy related to low-grade intracerebral neoplasms between 1984 and 1990. All patients had medically refractory partial seizures and a mass lesion identified on neuroimaging studies. Lesionectomy was performed on 17 patients, and 34 had lesion resection and corticectomy. Mean postoperative follow-up was 4.4 years (range 2-8 years). Sixty-six percent of patients were seizure-free, and 88% experienced a significant reduction in seizure frequency. In 16 patients (31%), antiepileptic drugs (AEDs) were successfully discontinued. Twenty-five of 31 (81%) eligible patients obtained a driver's license after successful operation. Patients with complete tumor resection and no interictal epileptiform activity on postoperative EEG studies had the best operative outcome. Epilepsy surgery can result in long-term improvement in seizure control and quality of life (QOL) in selected patients with intractable tumor-related epilepsy. Our results should be useful to clinicians considering treatment options for patients with intractable seizures related to low-grade intracerebral neoplasms. PMID- 7988501 TI - Birth order, sibship size, and risk of epilepsy. AB - We examined the relation between epilepsy and birth order, using data on 1,950 probands with epilepsy and 4,636 of their full siblings without epilepsy from the Epilepsy Family Study of Columbia University. The proportion of first-born individuals appeared to be higher among probands with epilepsy than among their unaffected siblings, but this relation disappeared after we controlled for the confounding effect of sibship size. With sibship size controlled, the proportion of first-born individuals was similar to that in unaffected siblings for probands with idiopathic/cryptogenic epilepsy, generalized and partial onset seizures, and all ages at onset of epilepsy. Probands with remote symptomatic epilepsy had higher birth orders than their unaffected siblings, even after we controlled for sibship size. PMID- 7988503 TI - Prognostic significance of ictal and interictal epileptiform activity in temporal lobe epilepsy. AB - Long-term electrocorticograms (ECoG), recorded by chronically implanted subdural electrodes during preoperative evaluation of 59 patients with temporal lobe epilepsy (TLE) were analyzed retrospectively to assess the prognostic relevance of distribution of interictal epileptiform potentials (IEP) and seizure origin (SO) and to investigate factors affecting their lateralization. Subsequent to preoperative evaluation, a standardized two thirds anterotemporal lobectomy including subtotal hippocampectomy had been performed in all patients. The following results were obtained: (a) Only patients with 100% lateralization of SO and IEP had excellent seizure outcome (= 89% seizure-free); (b) patients with bitemporal SO were unlikely to benefit from surgical treatment (= 12.5% seizure free); (c) 40-56% patients with unilateral temporal SO and bitemporal IEP, became seizure-free irrespective of the degree of lateralization of IEP; and (d) multidimensional analysis of variance showed that lateralization of SO, presence of a magnetic resonance imaging (MRI)-detectable lesion, presence of hippocampal sclerosis, presence of febrile seizures and seizures at age < or = 6 years are the five most important variables indicating abolition of seizures. Combined analysis of ECoG-recorded SO and IEP allows prediction of postoperative seizure control within close boundaries. PMID- 7988502 TI - Treatment of severe myoclonic epilepsy in infants with bromide and its borderline variant. AB - We studied the efficacy of bromides (BR) as add-on therapy in 11 patients with severe myoclonic epilepsy in infants (SME) and in another 11 with the borderline variant of SME (BVSME). Study subjects were aged 8.5-183 months (mean 64.4 months). Longest duration of BR treatment was 37 months (range 4-37 months; mean 19.7 months). Eight of 22 (36%) of patients with generalized tonic-clonic seizures (GTCS) had an excellent effect (> 75% reduction in total seizure frequency or duration) and 9 (41%) had a moderate effect (50-75% reduction) 3 months after introduction of BR. Twelve months after initiation of BR. 5 of the patients with significant improvement were no longer responsive; ultimately, therefore, 6 had an excellent effect and 2 had a moderate effect. Of those with partial seizures (n = 5) and myoclonic/absence seizures (n = 5), only 1 patient in each group showed a moderate effect at the 12-month time-point. Dosages and serum concentrations of BR ranged from 30 to 100 mg/kg (mean 58 mg/kg) and from 64 to 159 mg/dl (mean 101 mg/dl), respectively. Of the 12 patients experiencing side effects, including drowsiness, appetite loss, and skin rash, 1 required a reduction in BR dosage because of an extensive acneiform rash on the face. The results show that BR treatment holds promise for patients with SME and BVSME and should therefore be investigated further. PMID- 7988504 TI - EEG changes and seizure exacerbation in young children treated with carbamazepine. AB - Carbamazepine (CBZ) has been reported to exacerbate some seizure types in children. We studied the correlation between CBZ-associated EEG changes and seizure exacerbation in 59 children aged < 6 years treated with CBZ. All patients had EEGs before and after initiation of treatment; initial EEGs were not significantly different among the patients. In 33 children (56%), the subsequent EEGs were either unchanged or improved or demonstrated minor changes (Group I), and excellent to complete seizure control was achieved in 67% of patients. In 26 children (44%), the EEG became significantly more abnormal and was characterized predominantly by new appearance of generalized spike/polyspike-and-wave discharges (group II). The majority of these patients (65%) experienced seizure exacerbation (p < 0.001). For group I, symptomatic partial epilepsy, idiopathic focal epilepsy, and complex febrile seizures were significantly more common; in group II, cryptogenic seizure disorders were more common (p < 0.005). Children in group I were more likely to remain on CBZ or to be weaned from medication after successful treatment, whereas children in group II required additional medication(s) or complete discontinuation of CBZ. Our results suggest that new appearance of generalized paroxysmal discharges after treatment is highly correlated with seizure exacerbation or suboptimal control as well as with adverse outcome. Conversely, absence of significant EEG deterioration on CBZ is usually associated with good seizure control. PMID- 7988505 TI - Relationship of carbamazepine reduction rate to seizure frequency during inpatient telemetry. AB - To establish guidelines for medication reduction during inpatient telemetry, the records of 18 children and young adults with refractory partial seizures undergoing carbamazepine (CBZ) reductions during continuous video/EEG telemetry were reviewed. Six patients were receiving CBZ monotherapy, and 12 patients were treated with an additional antiepileptic drug (AED) maintained at baseline dosage during CBZ taper. Despite relatively rapid mean reductions in dosage of 44% by day 2 of taper, no patients experienced frequent repetitive seizures or status epilepticus (SE). Seizure rate during the entire CBZ reduction period correlated significantly with rate of drug reduction. Linear regression analysis showed drug reduction rate to be a good predictor of seizure rate. Fourteen patients experienced at least three seizures during CBZ taper. On the average, the third seizure occurred on day 5 of taper at a percentage of dose reduction of 79%. In 8 patients, CBZ concentrations were measured both before taper and < or = 24 h after the third seizure. For these patients, seizure rate also correlated significantly with reduction in CBZ level. We conclude that manipulation of CBZ dose reduction rate is important in maximizing seizure frequency during telemetry and, in our patients, a relatively rapid rate of dose reduction was safe and effective in promoting seizure recordings. PMID- 7988506 TI - Postoperative EEG and electrocorticography: relation to clinical outcome in patients with temporal lobe surgery. AB - To evaluate the role of different EEG methods with respect to postoperative clinical follow-up, 32 non-lesionary epilepsy patients who had undergone temporal lobectomy were studied preoperatively and at 2-week, 3-month, and 1-year postoperative follow-up. Routine, sleep, and sphenoidal EEG recordings as well as intraoperative electrocorticography (ECoG) were made for all patients. At 1-year follow-up, the EEGs with sphenoidal electrodes and with sleep deprivation procedure provided important prognostic information; the appearance of seizures was associated with the presence of interictal epileptiform abnormalities in EEG. In the postresection ECoG, however, epileptiform abnormalities were not associated with clinical outcome or with postoperative epileptiform EEG at 1 year. Routine EEG reliably reflects clinical outcome after temporal lobectomy; with sphenoidal electrodes as well as with sleep deprivation procedure, the diagnostic yield can be further improved. PMID- 7988507 TI - Quantitative analysis of seizure frequency 1 week and 6, 12, and 24 months after surgery of epilepsy. AB - We made quantitative analysis of seizure frequency 1 week and 6, 12, and 24 months after seizure surgery. Seizure recurrence was significantly higher when seizures occurred in the first postoperative week. Seizure recurrence increased progressively with longer follow-ups, but the 6 month postoperative follow-up period was an excellent index of long-term outcome. In operative follow-up studies, seizure frequency should be reported at fixed follow-up periods, e.g., at 6 months and 1, 2, 5, and 10 years. Meaningful comparison of outcomes between different studies is possible only when reports include outcome at fixed postoperative follow-up periods (as opposed to ranges of follow-up periods). PMID- 7988508 TI - Degree of hippocampal neuron loss determines severity of verbal memory decrease after left anteromesiotemporal lobectomy. AB - Fifty-eight left speech dominant adults with medically refractory epilepsy originating from the temporal lobe (28 left, 30 right) were examined using the verbal Selective Reminding Test before and after anteromesiotemporal lobectomy. After neuron density in the excised hippocampal tissue was established, a median split procedure was performed to distinguish patients with severe neuron loss (13 left, 16 right) from those with only mild or moderate neuron loss (15 left, 14 right). The memory of patients with severe left hippocampal neuron loss did not decrease significantly postoperatively. Patients with mild or moderate left hippocampal neuron loss experienced significant verbal memory decrease postoperatively. The magnitude of the verbal memory decrease was not related to recurrence of seizures after operation. Patients undergoing right anteromesiotemporal lobectomy exhibited significant improvements in verbal memory, regardless of the condition of the excised hippocampal tissue. The degree of hippocampal neuron loss determines to a great extent the severity of the verbal memory decrease that follows dominant anteromesiotemporal lobectomy. PMID- 7988509 TI - Imaging studies in partial epilepsy in children and adolescents. AB - We reviewed the results of imaging studies on 111 children and adolescents with partial epilepsy to determine which imaging procedure had the greatest sensitivity and specificity for partial epilepsy in this age range. All cases were classified as idiopathic, lesional, and cryptogenic epilepsy based on the 1989 International League Against Epilepsy Classification. All patients had magnetic resonance imaging (MRI) and 98 also had computed tomography (CT). Thirty patients with negative CT had MRI lesions that were most likely the cause of the epilepsy, and the initial diagnosis of cryptogenic partial epilepsy was changed to lesional partial epilepsy. We concluded that CT use is unwarrantedly common. MRI should be considered the procedure of first choice. CT has a complementary role, and functional neuroimaging should be encouraged. PMID- 7988510 TI - Functional magnetic resonance imaging in partial epilepsy. AB - Functional magnetic resonance imaging (FMRI) detects signal changes in brain that accompany regional changes in neuronal activity. In normal human brain, FMRI shows changes in signal in the postcentral gyrus or superior temporal gyrus that correlate with voluntary motor activity or language processing, respectively. The model used to explain the changes in signal linked temporally with cerebral activity is a reduction in cerebral capillary deoxyhemoglobin concentration due to the increased blood flow that accompanies neuronal activity in the cerebrum. FMRI has been used in normal subjects but not extensively in patients. To determine the feasibility of using FMRI to map cerebral functions in patients with partial epilepsy syndromes, we performed a pilot study, using FMRI to identify signal changes in motor and language areas in response to tasks that activate those areas. Signal changes in epilepsy patients approximated those observed in volunteers. We conclude that FMRI can be developed as a method for functional cerebral mapping in partial epilepsies. PMID- 7988512 TI - Altered responsiveness during hyperventilation-induced EEG slowing: a non epileptic phenomenon in normal children. AB - The relation between hyperventilation (HV)-induced high-amplitude rhythmical slowing (HIHARS) and altered responsiveness without generalized spike and wave activity has not been clearly defined. To test whether altered responsiveness is a nonspecific physiologic response rather than a symptom of generalized epilepsy, we assessed verbal recall ability and motor response testing in 12 healthy nonepileptic children (mean age 9.6 years). Both tasks were administered as a baseline before HV, during HV but before onset of EEG slowing, and during HIHARS. Verbal recall and motor responsiveness remained unchanged during baseline and HV before onset of slowing. During HIHARS, all children exhibited impaired verbal recall (p < 0.005) and 8 of 12 failed to respond to repeated auditory clicks (p < 0.005). Our findings indicate that in a normal setting, responsiveness may be impaired during HV in healthy nonepileptic children. PMID- 7988511 TI - Hyperventilation activation on EEG recording in childhood. AB - In 66 children with no neurologic symptoms, we analyzed EEG slowing quantitatively during standardized hyperventilation (HV) activation [respiration rate (RR) of 30/min, threefold increase of VE, and 4-min duration]. Changes in cerebral blood flow (CBF) and velocity were also monitored in right common carotid artery by Doppler ultrasonic method. Decreases in PCO2 and CBF were the fundamental factors producing EEG slowing during HV. The degree of EEG slowing was greater in younger children and well proportional to age with such standardized HV. The decrease in CBF was much greater in younger children at the beginning of HV and may be related to the significant EEG slowing. EEG slowing was not related to the degree of decrease in CBF. The age difference in EEG response to HV in children and adults may be due to the differences in the decrease in the CBF volume and sensitivity of the CNS to the change in CBF. PMID- 7988513 TI - Video material and epilepsy. AB - Nine patients who had epileptic attacks while playing computer games were studied in the laboratory. Patients had an EEG recorded as well as their response to intermittent photic stimulation (IPS) at flash rates of 1-60 fps. In addition, pattern sensitivity was assessed in all patients by a gratings pattern. Only 2 patients had no previous history of convulsions, and only 2 had a normal basic EEG. All but 1 were sensitive to IPS, and all but 1 were pattern sensitive. Most patients were male, but although this appears to conflict with previously published literature results regarding the sex ratio in photosensitivity, it was due to the male predominance of video game usage. We compared our results with those reported in the literature. Diagnosing video game epilepsy requires performing an EEG with IPS and pattern stimulation. We propose a standard method of testing. PMID- 7988514 TI - Liver enzyme induction and serum lipid levels after replacement of carbamazepine with oxcarbazepine. AB - We evaluated liver P450 enzyme system induction and serum lipid levels in a prospective follow-up study in 12 male patients with epilepsy after replacing carbamazepine (CBZ) medication with oxcarbazepine (OCBZ). Antipyrine(t1/2) increased and antipyrine(CL) decreased 2 months after the medication was changed, reflecting normalization of liver P450 enzyme system function. Furthermore, serum total cholesterol levels decreased, but serum concentrations of high-density lipoprotein (HDL)-cholesterol and triglycerides (TG) were unchanged. OCBZ may be the preferable antiepileptic drug (AED) with regard to the effects of the medication on lipid metabolism. PMID- 7988515 TI - A comprehensive study of the relation between serum concentrations, concentration ratios, and level/dose ratios of carbamazepine and its metabolites with age, weight, dose, and clearances in epileptic children. AB - We made a comprehensive study of the relation between age, weight, carbamazepine (CBZ) dose, total clearance (TC), and intrinsic clearance (IC) and concentrations, concentration ratios, and level/dose ratios of CBZ, carbamazepine 10,11-epoxide (CBZ-E) and trans-10,11-dihydroxy-10,11- dihydro-carbamazepine (CBZ H) in a group of epileptic children receiving CBZ monotherapy. Body weight and age showed negative correlations with TC, IC, CBZ dose, and CBZ-E/CBZ and CBZ H/CBZ concentration ratios, and had positive relation with CBZ, CBZ-E, and CBZ-H level/dose ratios. These results indicate decreased CBZ metabolism with patient maturity. Correlations between CBZ dose with TC, IC, and the concentration ratios of CBZ-E/CBZ, CBZ-H/CBZ-E, and CBZ-H/CBZ were positive. CBZ dose also had negative associations with CBZ and CBZ-E level/dose ratios, indicating dose dependent autoinduction of CBZ metabolism. Our data suggest that weight, age, and CBZ dose have less influence on epoxide-hydrolase activities than on epoxidase activities. The CBZ-E/CBZ concentration ratio can be used as an indicator of the degree of autoinduction of CBZ metabolism, even in patients receiving CBZ monotherapy. PMID- 7988516 TI - Cost of epilepsy in the United States: a model based on incidence and prognosis. AB - A model of the clinical course of epilepsy from onset until remission or death has been developed for six prognostic groups, including survival, use and cost of medical care, and time lost from work and housekeeping. The model has been used to generate preliminary estimates of the lifetime cost of epilepsy for a cohort of persons diagnosed in 1990 in the United States. The distribution of incident cases among prognostic groups is derived from epidemiologic studies of prognosis in epilepsy. Direct cost is estimated by multiplying nationally representative unit costs by the expected type and frequency of medical care use. The latter were derived by an expert panel, based on inferences from existing literature and on their own clinical experiences. Indirect cost is estimated based on lost earnings associated with projections of restricted activity days, excess unemployment, and excess mortality. Total lifetime cost in 1990 dollars of all persons with epilepsy onset in 1990 was estimated at $3.0 billion, with indirect cost accounting for 62% of the total. Cost per patient ranged from $4,272 for persons with remission after initial diagnosis and treatment to $138,602 for persons with intractable and frequent seizures. Antiepileptic drug (AED) treatment is the most costly category of service. Different assumptions about the amount and type of drug administration cause major changes in overall cost estimates. PMID- 7988517 TI - Management and attitudes of epilepsy by a group of Sydney general practitioners. AB - Previous surveys of general practitioners (GPs) have shown stereotypic attitudes and management of persons with epilepsy (PWE). We mailed a questionnaire to 107 GPs in the Sydney and Illawarra regions of Australia to evaluate changes in knowledge and management of epilepsy and attitudes of GPs toward PWE as compared with results of a similar study made 10 years previously. Most GPs referred patients with epilepsy to a neurologist for initial management in preference to initiating investigation and treatment themselves. GPs were very satisfied with their sharing of care with neurologists, but indicated their high level of dissatisfaction with other health care therapists because of impractical advice and lack of empathy. The GPs' objectives of continuing management were mainly to prevent seizures, monitor of medication and its effects, and reduce the impact of patients' epilepsy on their daily life. Although many GPs believed that PWE were more likely to have emotional and relationship problems, most also believed that such persons contribute equally to society and can have normal quality of life (QOL). Although the GPs prefer to use a neurologist for initial management of PWE, they see themselves as having a role in continuing care and providing psychosocial support. The stereotyped perceptions of GPs indicated in the previous study have improved, although in some respects they remain negative. This study offers an audit of the outcome of a decade of educational promotion regarding epilepsy. PMID- 7988518 TI - Physical exercise, stressful life experience, and depression in adults with epilepsy. AB - Adults with epilepsy completed self-report measures of exercise participation, barriers to exercise, stressful life experience, depression, and general psychosocial adjustment (n = 133) as part of routine outpatient visits. Descriptive statistics showed lower levels of depression among patients who exercised regularly. Structural equation analyses confirmed the fit of a path model that included significant direct effects of exercise and stressful life experience on depression. These effects were independent of each other, and independent of the influence of other predictor variables, such as seizure frequency, age, and gender. Stressful life experience also had a direct unique effect on seizure frequency in the multivariate models. These results suggest that problems with depression, which are common in adults with epilepsy, are significantly lower among those who exercise regularly and avoid stressful life change. PMID- 7988519 TI - Physical exercise in women with intractable epilepsy. AB - Fifteen women with pharmacologically intractable epilepsy were given physical exercise (aerobic dancing with strength training and stretching) for 60 min, twice weekly, for 15 weeks. Seizure frequency was recorded by the patients for 3 7 months before the intervention, during the intervention period, and for 3 months after the intervention. Medication and other known seizure-influencing factors were kept as constant as possible. Self-reported seizure frequency was significantly reduced during the intervention period. The exercise also led to reduced level of subjective health complaints, such as muscle pains, sleep problems, and fatigue. The exercise reduced plasma cholesterol ratio and increased maximum O2 uptake. Because most of the patients were unable to continue the exercise on their own after the intervention period, the exercise effects were not maintained during the follow-up period. The patients were not unwilling to continue the exercise, but it was not sufficient to offer them the possibility of continuing similar types of exercise. We believe that 15 weeks is too short a time to establish a life-style change and that continued physical exercise for these patients requires a well-organized and supportive program, requiring experienced and dedicated instructors. PMID- 7988520 TI - Washington Psychosocial Seizure Inventory: a multiinstitutional study in Japan. AB - No reports of the Washington Psychosocial Seizure Inventory (WPSI) have yet been presented from Asian countries in detail. We performed a multiinstitutional study of this test in 652 Japanese subjects. The mean value of the Lie Scale was high, and only one third of our subjects were under the limit of the original criterion; this has been the biggest obstacle to use of the validity scales of this test in Japan. The profile form of the clinical scales was very similar to those reported from other countries. According to the relation between clinical characteristics and the WPSI scales, seizure frequency showed the strongest influence. In a comparison of whole subjects, mean scores of the clinical scales in Japan remained at an intermediate value or lower. This result was obviously distorted by the high score of the Lie Scale. When comparison was restricted to cases with valid Lie Scale scores, the values of five clinical scales showed high levels. Therefore, Japanese patients among developed countries apparently showed relatively severe levels of problems. We conclude that the WPSI could be a useful examination in Japan to determine reliably the various psychosocial problems of epileptic persons, but use of the Lie Scale according to the original criterion is not practical. Modifications of the limitation may be needed. PMID- 7988521 TI - Clinimetric analysis of treatment objectives and clinical status: individualized treatment in epileptic patients. AB - The achievement of treatment objectives for patients with epilepsy, as defined by the treating clinicians, was compared with scoring of clinimetric indexes. Patients with the treatment objectives "complete seizures remission" or "treatment impairment/benefit balance" were included in this study. The clinimetric indexes were also compared with a clinical status rating, as assessed by the clinician. No correlation was observed between clinimetric indexes and achievement of the treatment objective. The difference noted in outcome of treatment objectives and index scores may have resulted because the indexes were group-intended and the clinician's judgment was individual-oriented. The clinician's assessment of clinical status of the patient did correlate with the composite index of impairments (CII), however, a clinimetric scale for severity of impairments caused by epilepsy. The advantage of the CII over the clinical status rating is that the CII is constructed with objective data and shows the cause of change observed during follow-up. PMID- 7988522 TI - Nerve fiber size-related block of action currents by phenytoin in mammalian nerve. AB - We investigated nerve fiber size-related actions of phenytoin (PHT) by applying the anticonvulsant on 2-mm-long stretches of desheathed whole nerves, excised from rat sural nerve. Compound action potentials (APs) were elicited by voltage pulses of increasing amplitude and recorded as monophasic action currents of the A alpha beta-type along the surface of the nerve. The area under the action current Q at supramaximal stimulation was reduced by 11 and 30% in solutions containing 10 and 100 microM PHT, respectively, similar to the reduction in peak action current. However, a greater reduction in Q induced by PHT was observed with smaller stimuli at both concentrations. This stimulus-dependent reduction was believed to originate from selective inhibition of the thicker nerve fibers. Using a mathematical model, we separated Q into contributions Q alpha of the alpha-fibers and Q beta of the beta-fibers. In solutions containing 10 microM PHT, Q alpha was reduced by 15% maximally, whereas Q beta was not affected. Both fiber types were reduced < or = 30% in the presence of 100 microM PHT, whereas the relations between Q alpha and Q beta, respectively, and stimulus voltage shifted along the voltage axis for 0.3 V, suggesting that the larger fibers in the A alpha beta-groups were more inhibited by PHT than the smaller ones. Abolition of the early phases of the compound action currents by PHT also indicated loss mainly of faster conducting nerve fibers. We conclude that primarily the larger fibers in the A alpha beta populations were inhibited by the anticonvulsant, strongly suggesting a differential mode of action by PHT on myelinated nerve fibers. PMID- 7988523 TI - Ontogeny of feline temporal lobe epilepsy. III: Spontaneous sleep and arousal disorders in amygdala-kindled kittens. AB - We report the ontogeny and persistence of sleep and arousal disorders in amygdala kindled kittens. We also identify procedural differences that may explain discrepancies in the literature on postkindling sleep disorders. The study population consisted of 12 preadolescent kittens kindled between 2.5 and 6.5 months of age, 8 of which were followed to adulthood (> or = 1 year), and 8 unkindled implanted control animals. Sleep and seizure patterns were monitored on 12-24-h polygraphic or split-screen video recordings of EEG and behavioral activity. Kindled kittens displayed spontaneous seizure and interictal sleep anomalies that persisted to adulthood, as follows. As compared with neurosurgical controls, kindled kittens exhibited slow-wave sleep (SWS) and REM sleep insomnia at least 1 year after kindling and 1-5 months after convulsions, regardless of postictal recording delay. Sleep and arousal defects in kindled kittens were similar to but more pronounced than those in kindled adult cats, possibly because kittens spontaneously became epileptic. Detection of postkindling SWS insomnia could be masked by brief scoring epochs (less than the preferred 1-min epoch for cats); recurrent behavioral arousals after kindling frequently aborted 1-min SWS epochs but often did not interrupt 30-s SWS epochs (based on 1-min vs. 30-s minimum duration scoring criteria). Detection of postkindling REM sleep insomnia could be masked in kittens with alternating patterns of REM loss and REM rebound; all these kittens showed periodic bouts of REM onset from waking after kindling. Different data collection and analysis procedures influence detection of sleep and arousal disorders in amygdala-kindled cats when replication of findings is attempted. We conclude that these differences explain some controversies regarding the nature and prevalence of sleep disturbances in the kindling literature in temporal lobe epilepsy (TLE). PMID- 7988524 TI - Kindling induces transient changes in neuronal expression of somatostatin, neuropeptide Y, and calbindin in adult rat hippocampus and fascia dentata. AB - Fully hippocampus-kindled rats were examined 1 day and 1 month after the last stimulation for changes in somatostatin (SS)-, neuropeptide Y (NPY)-, and calbindin (CaBP)-immunoreactivity (ir) and SS- and NPY-mRNA in situ hybridization (ISH). One day after the last stimulation, there was marked, bilateral increase in SS- and NPY-ir in the outer part of the dentate molecular layer. The cell bodies of dentate hilar SS- and NPY-containing neurons, known to project to this area, also appeared to display increased immunoreactivity as well as an increased ISH signal for SS and NPY mRNA. Bilateral de novo expression of NPY-ir in dentate mossy fiber projection to dentate hilus and CA3 was also evident, but we noted no corresponding NPY-mRNA signal in the parent cell bodies, the dentate granule cells. After 1 month, the levels of NPY-ir and ISH signal appeared essentially normal. In contrast, the levels of SS apparently were decreased, although not yet normal. CaBP-ir was markedly and selectively reduced in dentate granule cell bodies, dendrites, and mossy fibers 1 day after the last stimulation, but after 1 month CaBP-ir appeared essentially normal. Because kindling, once established, is a permanent phenomenon, the observed transient changes in SS, NPY, and CaBP in specific hippocampal terminal fields and neuronal populations cannot be associated specifically with kindling. Rather, they relate to the repeated high frequency stimulations and may serve as protective measures against deleterious effects of such stimulations. PMID- 7988525 TI - Electrical stimulation of the mammillary nuclei increases seizure threshold to pentylenetetrazol in rats. AB - High-frequency electrical stimulation of mammillary nuclei (MN) of rat posterior hypothalamus resulted in a significant increase in seizure threshold induced by pentylenetetrazol (PTZ). The anticonvulsant effect was frequency and intensity specific. Stimulation at 100 Hz (1-5 V, 30-200 microA) afforded protection against EEG and behavioral manifestations of PTZ seizures. Stimulation of either low frequency (5 Hz), high intensities (8-20 V, 300-800 microA), or outside the histologically verified MN target region did not increase seizure threshold. In some instances, high-intensity stimulation of MN alone elicited spike-wave epileptiform EEG activity accompanied by either arrest of behavior or myoclonic seizures. In animals with ongoing seizure activity, electrical stimulation of MN disrupted the high-voltage synchronous wave forms on cortical EEG. These data support the concept that electrical perturbation of MN in hypothalamus may functionally inhibit generalization of paroxysmal activity required for expression of the EEG and, in particular, the behavioral component of PTZ seizures. These studies provide additional insight into forebrain-brainstem interactions mediating generalized seizure expression. PMID- 7988526 TI - Intractable complex partial seizures associated with posterior cerebral artery giant aneurysm: a case report. AB - Giant aneurysms have rarely been reported in association with intractable complex partial seizures (CPS). We report a 30-year-old man with intractable CPS since age 18 years. Seizure onset was electrically localized to right temporal lobe. Preoperative neuroimaging studies showed a partially thrombosed giant aneurysm of the right posterior cerebral artery. Selective amygdalohippocampectomy and occlusion of the posterior cerebral artery did not cause deficits. The patient has been seizure-free for 15 months after operation. We review the relevant literature on aneurysms as a cause of epilepsy. PMID- 7988527 TI - Reversible amnesia associated with a left temporal hematoma in a case of right temporal complex partial seizures. AB - We report the case of a 44-year-old woman with complex partial seizures (CPS) of right frontotemporal origin who developed generalized amnesia after undergoing intracranial electrode implantation complicated by left hippocampal hemorrhage. Serial memory testing disclosed recovery from the amnesic disorder, while repeated magnetic resonance imaging (MRI) showed resolution of her left hippocampal hemorrhage in a 2-month period. A second intracarotid amytal procedure confirmed the capability of her left temporal region to support memory. Consequently, a right orbitofrontotemporal lobectomy was performed without complication. PMID- 7988529 TI - Magnetic resonance imaging evidence of hippocampal sclerosis in progression: a case report. AB - A 32-month-old child presented in status epilepticus (SE) involving the left side of the body. Fast spin-echo magnetic resonance imaging (FSE-MRI) with hippocampal volumetry performed < or = 24 h after the seizure showed increased T2 signal of the right hippocampus, but no atrophy. Complex partial seizures (CPS) appeared at age 33 months, and three more episodes of SE occurred between 33 and 37 months of age. Follow-up FSE-MRI at 34 and at 45 months of age demonstrated progressive hippocampal atrophy with resolution of the increased T2 signal. Her CPS became intractable and, at age 51 months, she underwent right temporal lobectomy. In the ensuing 5 months, she has had only one major motor seizure. This case demonstrates that acute increased hippocampal T2 signal intensity can occur soon after SE and hippocampal sclerosis (HS) may become evident within months in the setting of recurrent early childhood SE. This observation may support the hypothesis that early childhood SE can lead to HS. Furthermore, this case suggests that years of temporal lobe CPS may not be necessary for development of HS. PMID- 7988528 TI - Chronic localized encephalitis (Rasmussen's syndrome) preceded by ipsilateral uveitis: a case report. AB - Chronic localized encephalitis (Rasmussen's syndrome) developed in an 11-year-old girl 1 month after operation for residual cataract due to chronic uveitis that had appeared at age 9 years ipsilateral to the affected cerebral hemisphere. Although the pathogenesis of Rasmussen's syndrome remains unknown, our case provides additional evidence indicating that a viral ocular infection is a possible cause or part of the disorder. PMID- 7988530 TI - Agenesis of internal carotid artery associated with symptomatic partial epilepsy. AB - An 8-year-old Chinese girl had a first episode of symptomatic partial epilepsy at age 2 years. Despite regular treatment with antiepileptic drugs (AEDs), the seizures remitted and exacerbated. Epileptiform EEG discharges were evident, arising from the left centroparietal region. Magnetic resonance imaging (MRI) and computed tomography (CT) scan of the temporal bone and cerebral angiography demonstrated absence of the left internal carotid artery and ipsilateral bony carotid canal. Perfusion brain single photon emission CT (SPECT) with [99mTc] HMPAO showed a perfusion defect at the left posterior temporoparietal lobe. Brain ischemia due to agenesis of the left internal carotid artery (ICA) was speculated as the cause of the partial epilepsy. PMID- 7988531 TI - Simple dysphasic seizures as the sole manifestation of relapse in multiple sclerosis. AB - In a patient with multiple sclerosis (MS), dysphasic seizures were the only manifestation of a relapse. There was a strong correlation between time course of seizures and EEG, and between a localized EEG focus and a magnetic resonance imaging (MRI)-verified encephalitic plaque in the left temporal lobe. PMID- 7988532 TI - Odds and SODs of equine motor neuron disease. PMID- 7988533 TI - Laryngeal hemiplegia: a slap in the face for the 'slap test'? PMID- 7988534 TI - Studies of the effects of transporting horses: better to arrive than to travel. PMID- 7988535 TI - Review of 40 cases of lung abscesses in foals and adult horses. AB - A retrospective study of 40 horses with primary lung abscesses without pleuropneumonia showed that lung abscesses occurred predominantly in young horses, usually in foals aged < or = 6 months. Hyperfibrinogenaemia was present in all but 2 horses, and other common clinical and haematological findings were hyperthermia, tachycardia, polypnoea, and neutrophilic leucocytosis. The most common bacterial species isolated from transtracheal aspirates were Streptococcus zooepidemicus (20/34) and Rhodococcus equi (13/34). Most horses (23/27) discharged from the hospital were long term survivors. Of the 19 horses for which a follow up was available, 12 raced or performed the task for which they were intended. None of the indicators evaluated in this study could reliably predict the bacterial species involved or the outcome. PMID- 7988536 TI - Evaluation of the thoraco-laryngeal reflex ('slap test') as an indicator of laryngeal adductor myopathy in the horse. AB - A study was conducted over a 12 month period to assess the accuracy of the 'slap test' in the diagnosis of laryngeal adductor myopathy. The thoraco-laryngeal reflexes of 15 horses with no clinical signs of idiopathic laryngeal hemiplegia (ILH) were recorded using a video-endoscope. These 'slap test' responses were examined independently by 3 assessors. The horses were subsequently subjected to euthanasia and samples taken from the cricoarytenoideus lateralis (CAL) muscles for histopathological examination and assessment of denervation atrophy. Despite normal adductory responses, moderate to severe atrophy of the left CAL muscles was seen in 5 horses. The remaining horses had varying degrees of adductor myopathy, invariably worse in the left side of the larynx. The 'slap test' as performed in this study was therefore unable to differentiate between horses with moderate to severe muscle changes and those without, making it useless as a diagnostic test for adductor myopathy. The reason for the preservation in adductor function despite advanced histological atrophy of the muscle may lie in the degree of reinnervation found in the muscles. PMID- 7988538 TI - Equine hoof function investigated by pressure transducers inside the hoof and accelerometers mounted on the first phalanx. AB - The dampening of hoof impact was investigated by measuring the accelerations transmitted through structures of the hoof in horses trotting freely on an asphalt tarmac. The hoof dampened the vibrations transmitted to the first phalanx. Shoeing decreased the viscous dampening and increased the median power frequency and the maximal amplitude of the vibrations transmitted to the first phalanx. The pressure inside the digital cushion of the foreleg was recorded. The pressure dropped during the stance phase, indicating expansion of the hoof. The expansion of the hoof was not produced by frog or sole weight bearing because this would have increased the intra-digital cushion pressure. The pressure theory of hoof function must presumably therefore be rejected. Shoeing the horses augmented the intra-digital cushion pressure drop and probably impaired the movements of the hoof wall. PMID- 7988537 TI - Evaluation of the thoraco-laryngeal reflex ('slap test') as an aid to the diagnosis of cervical spinal cord and brainstem disease in horses. AB - A study was conducted over a 12 month period to assess the specificity and sensitivity of the 'slap test', using endoscopic evaluation, in the detection of cervical spinal cord and caudal brainstem lesions in horses. Fifteen ataxic horses were subjected to the 'slap test' and subsequently examined post mortem. Twelve out of the 15 had histopathological lesions consistent with their clinical signs. Thirteen horses with no history of neurological dysfunction and no histopathological evidence of cervical spinal cord or brainstem disease were used as controls. The laryngeal adductory responses exhibited by all horses were filmed and later scored independently by 3 assessors. The proportion of animals diagnosed with cervical spinal cord and/or brainstem disease, defined by histopathological criteria, was found to be statistically similar to the proportion with abnormal 'slap test' responses, using the McNemar chi-Square test. Despite statistical significance between proportions, sensitivity of the 'slap test' was low, 50% for the left side on both days and 58% for the right side. Specificity was higher, 69% (Day 1) and 75% (Day 2) for the left side and 75% (Day 1) and 69% (Day 2) for the right side. In contrast to this, conventional neurological examination was found to be 100% sensitive and 81% specific in the detection of lesions of histopathological significance in the cervical spinal cord/caudal brainstem. Agreement between scores for the 'slap test' from the same assessor on different days was good, with values for kappa of 0.59 to 0.85. In contrast, agreement between assessors on the 'slap test' score was poor, with kappa 0.35.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7988540 TI - Body position and direction preferences in horses during road transport. AB - It has been hypothesised that horses have a preference for facing backward in a trailer during road transport in order to minimise shifts of body weight due to accelerations and decelerations. To determine if horses have preferences for facing forward vs. backward in a horse trailer, the authors analysed the percentages of time horses spent in different body positions and directions while standing in a moving or parked horse trailer. Body positions and directions of 8 Thoroughbred geldings were videotaped while horses were transported singly and untethered in a 4-horse stock trailer over a 32 km route of country roads; or while the same horses were untethered in the same trailer stationary in a parking lot. Analysis of the logit-transformed percentages of time horses spent in different directions indicated that they spent significantly more time facing backward when the trailer was in motion, but not when it was parked. Several horses displayed strong individual preferences for the directions they faced during road transport. PMID- 7988539 TI - Effect of route of administration and age on the pharmacokinetics of amikacin administered by the intravenous and intraosseous routes to 3 and 5-day-old foals. AB - The suitability of the intraosseous (i.o.) route for drug administration to equine neonates was evaluated in a study comparing the pharmacokinetics of amikacin administered by the i.o. and intravenous (i.v.) routes. Using a cross over study design amikacin sulphate (7 mg/kg bwt) was administered i.o. or i.v. to 6 healthy foals at 3 and 5 days of age. Amikacin was instantaneously and completely absorbed after i.o. administration, achieving a mean +/- sd peak concentration (34.17 +/- 3.54 micrograms/ml) in the first sample collected 3 min after administration which was not significantly different from the mean +/- sd peak concentration (32.92 +/- 2.63 micrograms/ml) achieved after i.v. administration. The plasma amikacin concentration-time profiles for the i.o. and i.v. routes were not different and both were appropriately described by a 2 compartment open pharmacokinetic model. No significant differences attributable to route of administration were found in values for the major pharmacokinetic variables. The degree of inter-individual variation in values for indices of clearance was considerably greater than the degree of variation attributable to age. Despite this, values for body clearance (ClB) were significantly higher (P < 0.05) and values for area under the plasma amikacin concentration-time curve (AUC) and concentration of amikacin in plasma at 8 h [Cp(8h)] were significantly lower in 5- than in 3-day-old foals, indicating that amikacin was more rapidly cleared by the older foals. Technical difficulties were not encountered during i.o. needle placement in the medial aspect of the proximal tibia. Mild diffuse soft tissue swelling which developed at the i.o. site resolved completely within 1-2 months.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7988542 TI - Beta-glucuronidase and trypsin inhibitor capacity of tracheal lavage fluid as indicators of seasonal airway irritation in the horse. AB - The health of the respiratory tracts of 19 horses was studied for 11 months. The horses were placed into 3 groups (healthy, periodically diseased and continuously diseased) based on the measurements of blood gases, intrapleural pressure and on neutrophil content of tracheal mucus. Lysosomal enzymes (N-acetyl-beta-D glucosaminidase and beta-glucuronidase) and reflectors of the proteolytic system (plasmin, plasminogen, trypsin inhibitor capacity) were determined. beta glucuronidase appeared to be a good indicator of the presence of disease of the respiratory system. High beta-glucuronidase values were seen in horses with elevated numbers of neutrophils, elevated arterial alveolar and intrapleural differences as well as in diseased horses during the stabling period. Trypsin inhibitor capacity seemed to be lower in the diseased respiratory system, probably due to the increased consumption of trypsin inhibitors. PMID- 7988541 TI - The role of nitric oxide in the responses of equine digital veins to vasodilator and vasoconstrictor agents. AB - Isolated equine digital veins were examined in vitro to study the importance of the endothelium in the responses to both vasodilator and vasoconstrictor agents and to characterise the endothelial-derived mediators involved. Carbachol (Cch; 1 microM) and bradykinin (Bk; 1 nM) caused relaxation of U44069-induced tone by 79.5 +/- 0.35% and 73.7 +/- 4.0% respectively. Mechanical removal of the endothelium completely prevented relaxant responses to Cch and to Bk showing they were mediated by the endothelium. Treatment of veins with NG-nitro-L-arginine methyl ester (L-NAME; 30 and 300 microM) inhibited vasorelaxant responses to both Cch and Bk whereas the cyclooxygenase inhibitor, ibuprofen (10 microM) had no inhibitory effect. The inhibitory action of L-NAME on the relaxations produced by Cch was partly reversed by L-arginine (3 and 10 mM). Cch-relaxations were potentiated in the presence of super oxide dismutase (15 units/ml) and inhibited by methylene blue (10 microM). The vasorelaxant effects of ATP (0.01 microM to 0.1 mM) were not dependent on the presence of the endothelium and the selective P2y receptor agonist, 2-methylthio-ATP proved to be ineffective as a vasodilator. Removal of the endothelium did not enhance the vasoconstrictor effects of the alpha 1 adrenoceptor agonist phenylephrine (0.01 microM to 0.1 mM) and treatment with L-NAME (300 microM) did not change the vasoconstrictor responses to 5-HT (1 nM to 10 microM) or the alpha 2 adrenoceptor agonist BHT-920 (1 nM to 1 microM).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7988543 TI - Proximodorsal first phalanx osteochondral chip fragmentation in 336 horses. AB - The results of arthroscopic surgery in the treatment of osteochondral fragmentation of the proximodorsal aspect of the first phalanx and the influence of other fetlock joint lesions on prognosis were evaluated in 336 horses. Horses were classified as: 1) returning to previous use at the same or higher class of performance; 2) returning to previous use (regardless of class of performance); or 3) failing to return to previous use. Ninety-six horses (29%) had fragmentation alone; 140 horses (42%) had fragmentation and additional fetlock lesions, and 100 horses (29%) underwent concurrent carpal arthroscopy. Of the 100 horses that underwent carpal arthroscopy, 63 had proximodorsal first phalanx fragmentation alone and 37 had other fetlock lesions associated with the fragment. There was significant association between lesion type and return to previous use for the Thoroughbred racehorse group. There was also a significant association between lesion type and return to the same or higher class of racing for the Thoroughbred racehorse group. No significant association in return to previous use existed for racehorses vs. non-racehorses, Thoroughbred racehorses vs. Quarter Horse racehorses, single vs. multiple joint involvement, and single vs multiple fragmentation per joint. The Thoroughbred racehorses in this study were sensitive to additional fetlock or carpal lesions, as was exemplified by the significant effect lesion type had on outcome. PMID- 7988544 TI - Equine motor neuron disease: findings in 28 horses and proposal of a pathophysiological mechanism for the disease. AB - Over a three and one-half year period, 28 adult horses were diagnosed with equine motor neuron disease (EMND). The most commonly identified environmental risk factors for a horse having EMND were absence of grazing for more than a year and provision of poor quality hay. Quarter Horses were 5.4 times more at risk than other breeds but this was thought to be an epiphenomenon related to the frequency of Quarter Horses at boarding stables. Weight loss, excessive recumbency and/or trembling were the first signs noted. Other clinical diagnostic signs included: constant shifting of the weight in the rear limbs, abnormally low head carriage and muscle fasciculations. Excellent to ravenous appetites were present in all cases and marked coprophagia in some cases. Abnormally high serum concentration of muscle-derived enzymes was the only consistent serum chemistry abnormality found. Abnormal glucose absorption, increased cerebrospinal fluid total protein and intrathecal production of IgG were identified in a number of cases. Euthanasia was performed on 5 horses within 4 days of hospital admission, because of inability to stand or respiratory distress, and on 18 horses after the diagnosis had been completed. Five affected horses were maintained for observational purposes for periods of 9 months to over 2 years after the onset of clinical signs. They were given access to pasture and 2 were given supplemental vitamin E as the only therapy. Marked clinical improvement occurred in the 4 more acutely affected horses. Pathological findings, preference of type 1 muscle fibre atrophy and lipopigment accumulation within the capillary endothelium of the spinal cord of all cases, supported the hypothesis of EMND being an oxidative disease.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7988545 TI - Alpha tocopherol concentrations in clinically normal adult horses. PMID- 7988546 TI - Mechanical ventilation and management of botulism secondary to an injection abscess in an adult horse. PMID- 7988547 TI - Pituitary abscess and basilar empyema in 4 horses. PMID- 7988548 TI - Protein splicing: an analysis of the branched intermediate and its resolution by succinimide formation. AB - Protein splicing involves the excision of an internal domain from a precursor protein and the ligation of the external domains so as to generate two new proteins. Study of this process has recently been facilitated by the isolation of a precursor and a branched intermediate from a thermophilic protein splicing element expressed in a foreign protein context. Two aspects of protein splicing are examined in this paper. We demonstrate a succinimide at the C-terminus of the spliced internal protein, implicating cyclization of asparagine in resolution of the branched intermediate, and we identify an alkali-labile bond in the branched intermediate. A revised protein splicing model based on these experimental results is presented. PMID- 7988549 TI - Asymmetric binding of the 1- and 4-C=O groups of QA in Rhodobacter sphaeroides R26 reaction centres monitored by Fourier transform infra-red spectroscopy using site-specific isotopically labelled ubiquinone-10. AB - Using 1-, 2-, 3- and 4-13C site-specifically labelled ubiquinone-10, reconstituted at the QA site of Rhodobacter sphaeroides R26 reaction centres, the infra-red bands dominated by the 1- and 4-C = O vibration of QA are assigned in the QA(-)-QA difference spectra. The mode dominated by the 4-C = O vibration is drastically downshifted in the reaction centres as compared with its absorption frequency in free ubiquinone-10. In contrast, the mode dominated by the 1-C = O vibration absorbs at similar frequencies in the free and the bound forms. The frequency shift of the 4-C = O vibration is due to a large decrease in bond order and indicates a strong interaction with the protein microenvironment in the ground state. In the charge-separated state the mode dominated by the semiquinone 4-C = O vibration is characteristic of strong hydrogen bonding to the microenvironment, whereas the mode dominated by the 1-C = O vibration indicates a weaker interaction. The asymmetric binding of the 1- and 4-C = O groups to the protein might contribute to the factors governing different redox reactions of ubiquinone-10 at the QA site as compared with its reactions at the QB site. PMID- 7988550 TI - Subcellular relocalization of a long-chain fatty acid CoA ligase by a suppressor mutation alleviates a respiration deficiency in Saccharomyces cerevisiae. AB - We have isolated an extragenic suppressor, FAM1-1, which is able to restore respiratory growth to a deletion of the CEM1 gene (mitochondrial beta-keto-acyl synthase). The sequence of the suppressor strongly suggests that it encodes a long-chain fatty acid CoA ligase (fatty-acyl-CoA synthetase). We have also cloned and sequenced the wild-type FAM1 gene, which is devoid of suppressor activity. The comparison of the two sequences shows that the suppressor mutation is an A- >T transversion, which creates a new initiation codon and adds 18 amino acids to the N-terminus of the protein. This extension has all the characteristics of a mitochondrial targeting sequence, whilst the N-terminus of the wild-type protein has none of these characteristics. In vitro mitochondrial import experiments show that the N-terminal half of the suppressor protein, but not of the wild-type, is transported into mitochondria. Thus, we hypothesize that the suppressor acts by changing the subcellular localization of the protein and relocating at least some of the enzyme from the cytosol to the mitochondria. These results support the hypothesis that some form of fatty acid synthesis, specific for the mitochondria, is essential for the function of the organelle. PMID- 7988551 TI - Calcium-independent calmodulin requirement for endocytosis in yeast. AB - We have recently shown that actin and fimbrin are required for the internalization step of endocytosis in yeast. Using a yeast strain with a temperature-sensitive allele of CMD1, encoding calmodulin, we demonstrate that this protein is also required for this process. Calmodulin mutants that have lost their high-affinity calcium binding sites are, however, able to carry out endocytosis normally. A mutation in Myo2p, an unconventional myosin that is a possible target of calmodulin, did not inhibit endocytosis. The function of calmodulin in endocytosis seems to be specific among membrane trafficking events, because the calmodulin mutants are not defective for biogenesis of soluble vacuolar hydrolases nor invertase secretion. Calmodulin does not seem to play a major role in the post-internalization steps of the endocytic pathway in yeast. PMID- 7988552 TI - Specific interactions of Mss4 with members of the Rab GTPase subfamily. AB - Mss4 is a mammalian protein that was identified as a suppressor of a yeast secretory mutant harboring a mutation in the GTPase Sec4 and was found to stimulate GDP release from this protein. We have now performed a biochemical characterization of the Mss4 protein and examined the specificity of its association with mammalian GTPases. Mss4 is primarily a soluble protein with a widespread tissue distribution. Recombinant Mss4 binds GTPases present in tissue extracts, and by a gel overlay assay binds specifically Rab Rab10proteins. We further define the Mss4-GTPase interaction to a subset of Rabs belonging to the same subfamily branch which include Rab1, Rab3, Rab8, Rab10, Sec4 and Ypt1 but not Rab2, Rab4, Rab5, Rab6, Rab9 and Rab11. Accordingly, Mss4 co-precipitates from a brain extract with Rab3a but not Rab5. Mss4 only stimulates GDP release from, and the association of GTP gamma S with, this Rab subset. Recombinant Mss4 and Rab3a form a stable complex in solution that is dissociated with either GDP or GTP gamma S. Injection of Mss4 into the squid giant nerve terminal enhances neurotransmitter release. These results suggest that Mss4 behaves as a guanylnucleotide exchange factor (GEF) for a subset of Rabs to influence distinct vesicular transport steps along the secretory pathway. PMID- 7988553 TI - The cytoplasmic domain of CD4 plays a critical role during the early stages of HIV infection in T-cells. AB - The role played by the cytoplasmic domain of the CD4 molecule in the process of HIV infection was investigated, using A2.01 cells which express different forms of the CD4 gene. A delay in HIV production was consistently observed in cells expressing a truncated CD4 which lacks the cytoplasmic domain (CD4.401) compared with cells expressing the wild type CD4. The delay was much less in cells expressing a hybrid CD4-CD8 molecule (amino acids 1-177 of CD4 fused to the hinge, transmembrane and cytoplasmic domains of CD8). Yet the extent of viral entry and reverse transcription, monitored by semi-quantitative PCR, was similar in each cell type studied. For further study of the mechanism responsible for delayed HIV replication in the A2.01/CD4.401 cell line, cells were treated with phytohaemagglutinin (PHA), 24 h after HIV infection. Under such experimental conditions HIV production was detected at the same time in the culture supernatants of A2.01/CD4 and A2.01/CD4.401 cells. Moreover, we found that CD4 oligomerization by HIV-1 induced NF-kappa B translocation in A2.01/CD4 and A2.01/CD4-CD8 but not in A2.01/CD4.401 cells. This was consistent with CAT assay experiments which provided evidence for Tat-independent NF-kappa B mediated activation of HIV-1 LTR promoter after HIV binding to CD4 in A2.01/CD4 and A2.01/CD4-CD8 but not in A2.01/CD4.401 cells. In contrast to results published recently by Tremblay et al. (1994, EMBO J., 13, 774-783), we propose that a positive cellular signal initiated following oligomerization of the CD4 by the virus itself is involved in NF-kappa B-dependent early HIV transcription in A2.01/CD4 cells. PMID- 7988554 TI - Hyperplasia and tumours in lung, breast and other tissues in mice carrying a RAR beta 4-like transgene. AB - Transgenic mice were generated which express a truncated nuclear retinoic acid receptor beta (RAR beta), closely resembling the natural isoform RAR beta 4, under the control of the MMTV promoter. The transgene was expressed in salivary gland, testis, lung and mammary tissue in two different lines. At approximately 11-14 months virtually all the transgenic mice showed hyperplasia of the lung alveolar epithelium with an excess of type II pneumocytes. Hyperplasia of the mammary alveoli and terminal ducts was also seen in some females. Salivary glands and some sebaceous glands were hyperplastic in most male transgenic mice, but only rarely in females or in non-transgenics. Primary benign and malignant tumours were more numerous in transgenic mice than in controls, with a total of 23 in 43 mice versus two in 33 non-transgenic animals. Treatment with dexamethasone to increase transgene expression resulted in exaggerated versions of the above phenotypes. Overexpression of RAR beta 4 therefore appears to predispose various tissues to hyperplasia and neoplasia, and this by contrast to the RAR beta 2 isoform, which has tumour suppressor activity. A survey of ratios of RAR beta 4:RAR beta 2 expression in human lung tumour cell lines showed an increase compared with normal lung tissue, suggesting that RAR beta 4 may play a similar role in human tumorigenesis. PMID- 7988555 TI - Reconstitution and transphosphorylation of TGF-beta receptor complexes. AB - Transforming growth factor-beta (TGF-beta) signals by contacting two distantly related transmembrane serine/threonine kinases called receptors I (T beta R-I) and II (T beta R-II). TGF-beta binds to T beta R-II, which is a constitutively active kinase and this complex recruits T beta R-I, causing its phosphorylation and signal propagation to downstream substrates. The biochemical properties of this interaction were analyzed with reconstituted receptor systems. T beta R-I and T beta R-II baculovirally expressed at high levels in insect cells have the ligand binding properties of receptors expressed in mammalian cells, and form a complex in which T beta R-I phosphorylation is dependent on the kinase activity of T beta R-II. Furthermore, T beta R-I and T beta R-II can form a complex in vitro, and their cytoplasmic domains can specifically interact in a yeast two hybrid system. In vitro complex formation with catalytically active T beta R-II is necessary and sufficient for T beta R-I phosphorylation, which within this complex does not require the catalytic activity of T beta R-I, thus mimicking T beta R-I phosphorylation in intact cells. In addition, T beta R-I phosphorylated in vitro remains associated with T beta R-II. These results suggest that T beta R I and T beta R-II have affinity for each other, however, the ligand is required for stable complex formation under physiological conditions. Once formed, this complex is sufficient for T beta R-I phosphorylation by T beta R-II. PMID- 7988556 TI - Identification of Src, Fyn, Lyn, PI3K and Abl SH3 domain ligands using phage display libraries. AB - Many proteins involved in intracellular signal transduction contain a small, 50 60 amino acid domain, termed the Src homology 3 (SH3) domain. This domain appears to mediate critical protein-protein interactions that are involved in responses to extracellular signals. Previous studies have shown that the SH3 domains from several proteins recognize short, contiguous amino acid sequences that are rich in proline residues. While all SH3 recognition sequences identified to date share a conserved P-X-X-P motif, the sequence recognition specificity of individual SH3 domains is poorly understood. We have employed a novel modification of phage display involving biased libraries to identify peptide ligands of the Src, Fyn, Lyn, PI3K and Abl SH3 domains. With biased libraries, we probed SH3 recognition over a 12 amino acid window. The Src SH3 domain prefers the sequence XXXRPLPPLPXP, Fyn prefers XXXRPLPP(I/L)PXX, Lyn prefers RXXRPLPPLPXP, PI3K prefers RXXRPLPPLPP while the Abl SH3 domain selects phage containing the sequence PPPYPPPP(I/V)PXX. We have also analysed the binding properties of Abl and Src SH3 ligands. We find that although the phage-displayed Abl and Src SH3 ligands are proline rich, they are distinct. In surface plasmon resonance binding assays, these SH3 domains displayed highly selective binding to their cognate ligands when the sequences were displayed on the surface of the phage or as synthetic peptides. The selection of these high affinity SH3 peptide ligands provides valuable information on the recognition motifs of SH3 domains, serve as new tools to interfere with the cellular functions of SH3 domain-mediated processes and form the basis for the design of SH3-specific inhibitors of disease pathways. PMID- 7988558 TI - Altered transcriptional response to nutrient availability in hypovirus-infected chestnut blight fungus. AB - The gene lac-1, encoding the enzyme laccase, is one of several genes of the chestnut blight fungus, Cryphonectria parasitica, that are suppressed by virulence-attenuating mycoviruses of the hypovirus group. Two antagonistic regulatory pathways have been shown to govern the activity of the lac-1 promoter: a positive pathway that stimulates transcription and a negative pathway that represses transcription. We now report that these two regulatory pathways respond independently to specific changes in the nutritional environment. These newly defined conditions were used to confirm that a hypovirus suppresses the activity of the positive regulatory pathway, and to implicate calmodulin and calcineurin as components of the signal transduction cascades regulating lac-1 transcription. Significantly, lac-1 transcript accumulation was shown to be affected by amino acid availability. Further analysis revealed that transcriptional repression mediated by the negative regulatory pathway is relieved under conditions of amino acid deprivation. Thus, by blocking the positive pathway, hypovirus infection prevents increased lac-1 transcript accumulation in response to amino acid deficiency. These observations are consistent with the hypothesis that hypoviruses alter the transcriptional response of the host fungus to changes in nutrient availability. PMID- 7988557 TI - Activation of JAK kinases and STAT proteins by interleukin-2 and interferon alpha, but not the T cell antigen receptor, in human T lymphocytes. AB - The activation of Janus protein tyrosine kinases (JAKs) and signal transducer and activator of transcription (STAT) proteins by interleukin (IL)-2, the T cell antigen receptor (TCR) and interferon (IFN) alpha was explored in human peripheral blood-derived T cells and the leukemic T cell line Kit225. An IL-2 induced increase in JAK1 and JAK3, but not JAK2 or Tyk2, tyrosine phosphorylation was observed. In contrast, no induction of tyrosine phosphorylation of JAKs was detected upon stimulation of the TCR. IFN alpha induced the tyrosine phosphorylation of JAK1 and Tyk2, but not JAK2 or JAK3. IFN alpha activated STAT1, STAT2 and STAT3 in T cells, but no detectable activation of these STATs was induced by IL-2. However, IL-2 regulates the DNA binding and tyrosine phosphorylation of two STAT-like protein complexes which do not include STAT1, STAT2 or STAT3. STAT4 is not activated by IL-2. The activation of STAT5 cannot be excluded, so the IL-2-activated complexes most probably include at least one novel STAT. No STAT activity was detected in TCR-stimulated lymphocytes, indicating that the JAK/STAT pathway defined in this study constitutes an IL-2R mediated signaling event which is not shared by the TCR. Finally, in other cell types the correlation between JAK1 activation and the induction of STAT1 has suggested that JAK1 may activate STAT1. The observation that IL-2 and IFN alpha activate JAK1 to a comparable degree, but only IFN alpha activates STAT1, indicates that JAK1 activation is not the only determining factor for STAT1 activation. Moreover, the data show that JAK1 stimulation is also not sufficient for STAT3 activation. PMID- 7988559 TI - The Spi-1/PU.1 and Spi-B ets family transcription factors and the recombination signal binding protein RBP-J kappa interact with an Epstein-Barr virus nuclear antigen 2 responsive cis-element. AB - Epstein-Barr virus (EBV) immortalizes resting human B cells very efficiently in vitro. The EBV nuclear protein EBNA2 is absolutely required for this process. It also activates transcription of cellular, as well as viral, genes. It is assumed that EBNA2 contributes to B cell immortalization by its transactivating potential, since its transforming and transactivating functions could not be separated. Mutational analysis of the 80 bp EBNA2 responsive cis-element within the viral bidirectional LMP/TP2 promoter region identified two sequence elements, which are both essential for transactivation by EBNA2. These sequences harbour putative consensus binding sites for Spi-1 oncoprotein and recombination signal binding protein RBP-J kappa, the homologue of Drosophila Suppressor of Hairless. Electrophoretic mobility shift assays demonstrated the high affinity binding of Spi-1 and Spi-B, both members of the Ets family of transcription factors, to one sequence element. The other element bound RBP-J kappa with low affinity. In addition, co-transfections showed that the replacement of the Spi-1/Spi-B binding site in the bi-directional LMP/TP2 promoter by the analogous SV40 Spi-1 responsive element did not impair its function on EBNA2-mediated transactivation. It is concluded that the transcriptional regulators Spi-1 and Spi-B as well as RBP-J kappa play an essential role in transactivating the LMP/TP2 promoter by EBNA2 and therefore in the immortalization of B cells by EBV. PMID- 7988560 TI - The human J kappa recombination signal sequence binding protein (RBP-J kappa) targets the Epstein-Barr virus EBNA2 protein to its DNA responsive elements. AB - The Epstein-Barr virus (EBV) protein EBNA2, which is essential for the immortalization of human primary B cells by EBV, acts as a transcriptional activator of cellular and viral genes. Specific responsive elements have been characterized in several of the promoters activated by EBNA2. They all share the core sequence GTGGGAA. EBNA2 does not, however, bind to these sequences directly, but appears to be targeted to them by a cellular protein. A similar core sequence has recently been identified as a high-affinity binding site for the human recombination signal sequence binding protein RBP-J kappa. Here we provide evidence that RBP-J kappa binds to specific sequences in EBNA2-responsive elements. Our results also demonstrate that RBP-J kappa makes direct physical contact with EBNA2 in solution and recruits EBNA2 to its cognate DNA sequences, suggesting that RBP-J kappa may mediate EBNA2 transactivation of both cellular and viral genes. PMID- 7988561 TI - The DNA sequence specificity of HMG boxes lies in the minor wing of the structure. AB - To establish the basis of sequence-specific DNA recognition by HMG boxes we separately transferred the minor and major wings from the sequence-specific HMG box of TCF1 alpha into their equivalent position in the non-sequence-specific box 2 of HMG1. Thus chimera THT1 contains the minor wing (of 11 N-terminal and 25 C terminal residues) from the HMG box of TCF1 alpha and the major wing (the 45 residue central section) from HMG1 box 2, whilst the situation is reversed in chimera HTH1. The structural integrity of the two chimeric proteins was established by CD, NMR and their binding to four-way junction DNA. Gel retardation and circular permutation assays showed that only chimera THT1, containing the TCF1 alpha minor wing, formed a sequence-specific complex and bent the DNA. The bend angle was estimated to be 59 degrees for chimera THT1 and 52 degrees for the HMG box of TCF1 alpha. Our results, in combination with mutagenesis and other data, suggests a model for the DNA binding of HMG boxes in which the N-terminal residues and part of helix 1 contact the minor groove on the outside of a bent DNA duplex. PMID- 7988563 TI - MAZ-dependent termination between closely spaced human complement genes. AB - The zinc finger protein MAZ, originally identified as a factor that binds to the c-myc P2 promoter, is associated with transcriptional termination. As shown in these studies, a termination sequence between the closely spaced human complement genes C2 and Factor B contains a protein binding site which interacts with three different proteins in vitro. Binding of one of these factors, MAZ, correlates with activity of the C2 termination sequence in vivo. Cloned MAZ was used to obtain a consensus binding site, G5AG5. This allowed identification of new sites, between the closely spaced human genes g11 and C4 and within an intron of the mouse IgM-D gene, where termination is known to occur and regulate the expression of IgD. The g11 and IgM MAZ sites lie within sequences that have activity in a termination assay and, furthermore, mutation of C2 or g11 MAZ sites severely reduces termination activity. MAZ bends DNA, and inherently bent DNA is highly active as a terminator, suggesting that MAZ-induced bending is important for C2 and g11 termination. We propose that MAZ sites exist in promoters which require protection against transcriptional interference, such as those of closely spaced genes, to cause efficient termination. The MAZ consensus sequence will facilitate the identification of further sites. PMID- 7988562 TI - Modulation of tyrT promoter activity by template supercoiling in vivo. AB - We have found that initiation of RNA synthesis at the tyrT promoter of Escherichia coli can be stimulated on a plasmid by a factor of 4-6 by elevation of DNA supercoiling in vivo. Increased unconstrained plasmid supercoiling was achieved by inserting the tyrT promoter upstream of the tetracycline resistance gene tetA and transformation into a topA host. Under these conditions there is marked oversupercoiling of the plasmid DNA and we have shown previously that this can lead to increased promoter activity in the topological domain created. A critical element in the formation of this domain is the coupled transcription, translation and membrane insertion of tetA and we show that all of these events are important in the stimulation of tyrT promoter activity. The magnitude of the stimulation is in reasonable agreement with that measured in vitro as a function of plasmid supercoiling, if the unconstrained level of negative supercoiling in vivo is increased from a basal level of -sigma approximately 0.022 to -sigma approximately -0.052 by transcription-induced supercoiling. The induced supercoiling is very efficient, indicating that the tyrT promoter is itself contributing to the steady-state level despite a total lack of membrane anchorage for the tyrT transcription unit. This study provides a new example of the topological coupling of promoters. PMID- 7988564 TI - SPARC and thrombospondin genes are repressed by the c-jun oncogene in rat embryo fibroblasts. AB - The sequence-specific transcription factor c-Jun displays oncogenic potential in mammalian cells either in cooperation with activated Ras in primary embryonic fibroblasts or alone in established cell lines. Although pathways for signal transduction leading to activation of c-Jun proteins have been extensively studied, little is known about the events downstream of c-Jun stimulation. We isolated cellular genes that are targets of c-Jun by differential screening of a cDNA library from primary rat embryo fibroblasts. Two transcripts with sequences similar to known genes were repressed following transitory expression of a c-Jun encoding vector. They correspond to the SPARC and thrombospondin 1 (TS1) genes, encoding extracellular matrix proteins. These genes are tightly regulated during embryogenesis and in adult tissues and are involved in the control of cell growth. c-Jun transitory repression of these two genes was demonstrated both in primary cells and in FR3T3, an established fibroblast cell line. The repression was also detected in FR3T3 derivatives stably transformed by c-Jun or Ras. Although c-Jun regulation of the TS1 gene was found at the promoter level, preliminary results strongly suggest that repression of SPARC and TS1 gene expression are mediated by a secreted factor. In contrast, expression of these genes was unaffected by transformation with oncogenes from DNA viruses. Our results identify new, specific, probably indirect c-Jun target genes and suggest previously unsuspected regulatory roles for SPARC and thrombospondin in the control of cell growth. PMID- 7988566 TI - Disruption of RNA editing in Leishmania tarentolae by the loss of minicircle encoded guide RNA genes. AB - RNA editing in kinetoplastids appears to be a labile genetic trait that is affected by prolonged cell culture. The transcripts of the G1-G5 cryptogenes are pan-edited in the recently isolated LEM125 strain of Leishmania tarentolae, but not in the UC strain which has been in culture for 55 years. At least 32 minicircle-encoded guide RNAs (gRNAs) for the editing of G1-G5 transcripts are present in LEM125 and absent in UC. We hypothesize that specific minicircle sequence classes encoding gRNAs for the editing of these transcripts were lost during the long culture history of the UC strain. The protein products, which include components of complex I of the respiratory chain, are probably not required during the culture stage of the Leishmania life cycle. PMID- 7988565 TI - Regulation of mammalian spliceosome assembly by a protein phosphorylation mechanism. AB - Splicing of mRNA precursors (pre-mRNA) is preceded by assembly of the pre-mRNA with small nuclear ribonucleoprotein particles (snRNPs) and protein factors to form a splicesome. Here we show that stimulating Ser/Thr-specific protein dephosphorylation selectively inhibits an early step during mammalian spliceosome assembly. Treatment of HeLa nuclear splicing extracts with human protein phosphatase 1 (PP1) expressed in Escherichia coli, or PP1 purified from rabbit skeletal muscle, prevents pre-spliceosome E complex (early complex) formation and stable binding of U2 and U4/U6.U5 snRNPs to the pre-mRNA. PP1 does not inhibit splicing catalysis if added after spliceosome assembly has taken place. Addition of purified SR protein splicing factors restores spliceosome formation and splicing to PP1-inhibited extracts, consistent with SR proteins being targets regulated by phosphorylation. These data extend earlier observations showing that splicing catalysis, but not spliceosome assembly, is blocked by inhibiting protein phosphatases. It therefore appears that pre-mRNA splicing, in common with other biological processes, can be regulated both positively and negatively by reversible protein phosphorylation. PMID- 7988567 TI - Translational control by cytoplasmic polyadenylation of c-mos mRNA is necessary for oocyte maturation in the mouse. AB - The c-mos proto-oncogene product is a key element in the cascade of events leading to meiotic maturation of vertebrate oocytes. We have investigated the role of cytoplasmic polyadenylation in the translational control of mouse c-mos mRNA and its contribution to meiosis. Using an RNase protection assay we show that optimal cytoplasmic polyadenylation of c-mos mRNA requires three cis elements in the 3' UTR: the polyadenylation hexanucleotide AAUAAA and two U-rich cytoplasmic polyadenylation elements (CPEs) located 4 and 51 nucleotides upstream of the hexanucleotide. When fused to CAT coding sequences, the wild-type 3' UTR of c-mos mRNA, but not a 3' UTR containing mutations in both CPEs, confers translational recruitment during maturation. This recruitment coincides with maximum polyadenylation. To assess whether c-mos mRNA polyadenylation is necessary for maturation of mouse oocytes, we have ablated endogenous c-mos mRNA by injecting an antisense oligonucleotide, which results in a failure to progress to meiosis II after emission of the first polar body. Such antisense oligonucleotide-injected oocytes could be efficiently rescued by co-injection of a c-mos mRNA carrying a wild-type 3' UTR. However, co-injection of a c-mos mRNA lacking functional CPEs substantially lowered the rescue activity. These results demonstrate that translational control of c-mos mRNA by cytoplasmic polyadenylation is necessary for normal development. PMID- 7988568 TI - Architecture of telomerase RNA. AB - Telomerase, an essential ribonucleoprotein reverse transcriptase, adds telomeric DNA to the ends of eukaryotic chromosomes. We examined the conformational properties of the naked RNA moiety of telomerase from two related ciliates, Tetrahymena thermophila and Glaucoma chattoni. As well as finding evidence for features proposed previously on the basis of phylogenetic comparisons, novel conserved structural properties were revealed. Specifically, although the region around helix III was previously proposed to form a pseudoknot, our results indicate that in the naked RNA this region maintains a level of 'plasticity', probably in an equilibrium favoring one of two helices. In addition, these studies reveal that the templating domain is not entirely single-stranded as previously proposed, but is ordered due to constraints imposed by other parts of the RNA. Finally, our results suggest that the GA bulge in helix IV may introduce a structurally conserved kink. We now propose a 'two-domain' structure for the telomerase RNA based on function: one conformationally flexible domain, which includes the template and the region around helix III, involved with enzymatic function, and a second largely helical domain, including helices I and IV and the proposed kink, which may serve as a scaffold for protein binding. PMID- 7988569 TI - A mutant form of the Ran/TC4 protein disrupts nuclear function in Xenopus laevis egg extracts by inhibiting the RCC1 protein, a regulator of chromosome condensation. AB - The Ran protein is a small GTPase that has been implicated in a large number of nuclear processes including transport. RNA processing and cell cycle checkpoint control. A similar spectrum of nuclear activities has been shown to require RCC1, the guanine nucleotide exchange factor (GEF) for Ran. We have used the Xenopus laevis egg extract system and in vitro assays of purified proteins to examine how Ran or RCC1 could be involved in these numerous processes. In these studies, we employed mutant Ran proteins to perturb nuclear assembly and function. The addition of a bacterially expressed mutant form of Ran (T24N-Ran), which was predicted to be primarily in the GDP-bound state, profoundly disrupted nuclear assembly and DNA replication in extracts. We further examined the molecular mechanism by which T24N-Ran disrupts normal nuclear activity and found that T24N Ran binds tightly to the RCC1 protein within the extract, resulting in its inactivation as a GEF. The capacity of T24N-Ran-blocked interphase extracts to assemble nuclei from de-membranated sperm chromatin and to replicate their DNA could be restored by supplementing the extract with excess RCC1 and thereby providing excess GEF activity. Conversely, nuclear assembly and DNA replication were both rescued in extracts lacking RCC1 by the addition of high levels of wild type GTP-bound Ran protein, indicating that RCC1 does not have an essential function beyond its role as a GEF in interphase Xenopus extracts. PMID- 7988570 TI - Variable germline and embryonic instability of the human minisatellite MS32 (D1S8) in transgenic mice. AB - Tandem repeat loci such as minisatellites and trinucleotide repeats frequently show instability. We have investigated mutation at human minisatellite MS32 (locus D1S8) transferred to transgenic mice. Three lines of hemizygous transgenic mice were studied. A single-copy line (110D) was seen to be relatively stable, whilst two multicopy lines showed structural instability of the transgene in pedigrees (lines 109 and 110A). For both these lines, mutant structures were detected as a result of mutation events having occurred in the germline or early embryo. Structural changes seen included gain or loss of minisatellite repeat units (110A and 109), alteration of DNA flanking the minisatellite repeat array (109 only) or deletion of the entire transgene (109 only). This work demonstrates that tandem repeat transgenes can show instability and thus provide additional systems for the analysis of repetitive DNA structural change in mice. PMID- 7988571 TI - Changes in chromatin structure at recombination initiation sites during yeast meiosis. AB - Transient double-strand breaks (DSBs) occur during Saccharomyces cerevisiae meiosis at recombination hot spots and are thought to initiate most, if not all, homologous recombination between chromosomes. To uncover the regulatory mechanisms active in DSB formation, we have monitored the change in local chromatin structure at the ARG4 and CYS3 recombination hot spots over the course of meiosis. Micrococcal nuclease (MNase) digestion of isolated meiotic chromatin followed by indirect end-labeling revealed that the DSB sites in both loci are hypersensitive to MNase and that their sensitivity increases 2- to 4-fold prior to the appearance of meiotic DSBs and recombination products. Other sensitive sites are not significantly altered. The study of hyper- and hypo-recombinogenic constructs at the ARG4 locus, also revealed that the MNase sensitivity at the DSB site correlates with both the extent of DSBs and the rate of gene conversion. These results suggest that the local chromatin structure and its modification in early meiosis play an important role in the positioning and frequency of meiotic DSBs, leading to meiotic recombination. PMID- 7988572 TI - Purification and characterization of the human Rad51 protein, an analogue of E. coli RecA. AB - In bacteria, genetic recombination is catalysed by RecA protein, the product of the recA gene. A human gene that shares homology with Escherichia coli recA (and its yeast homologue RAD51) has been cloned from a testis cDNA library, and its 37 kDa product (hRad51) purified to homogeneity. The human Rad51 protein binds to single- and double-stranded DNA and exhibits DNA-dependent ATPase activity. Using a topological assay, we demonstrate that hRad51 underwinds duplex DNA, in a reaction dependent upon the presence of ATP or its non-hydrolysable analogue ATP gamma S. Complexes formed with single- and double-stranded DNA have been observed by electron microscopy following negative staining. With nicked duplex DNA, hRad51 forms helical nucleoprotein filaments which exhibit the striated appearance characteristic of RecA or yeast Rad51 filaments. Contour length measurements indicate that the DNA is underwound and extended within the nucleoprotein complex. In contrast to yeast Rad51 protein, human Rad51 forms filaments with single-stranded DNA in the presence of ATP/ATP gamma S. These resemble the inactive form of the RecA filament which is observed in the absence of a nucleotide cofactor. PMID- 7988573 TI - DNA-binding induces a major structural transition in a type I methyltransferase. AB - The type IC DNA methyltransferase M.EcoR124I is a complex multisubunit enzyme that recognizes the non-palindromic DNA sequence GAAN6RTCG. Small angle X-ray scattering has been used to investigate the solution structure of the methyltransferase and of complexes of the enzyme with unmethylated and hemimethylated 30 bp DNA duplexes containing the specific recognition sequence. A major change in the quaternary structure of the enzyme is observed following DNA binding, based on a decrease in the radius of gyration from 56 to 40 A and a reduction in the maximum dimension of the enzyme from 180 to 112 A. The structural transition observed is independent of the methylation state of the DNA. CD shows that there is no change in the secondary structure of the protein subunits when DNA is bound. In contrast, there is a large increase in the CD signal arising from the DNA, suggesting considerable structural distortion which may allow access to the bases targeted for methylation. We propose that DNA binding induces a large rotation of the two HsdM subunits towards the DNA, mediated by hinge bending domains in the specificity subunit HsdS. PMID- 7988574 TI - The mechanism of the stringent control of lambda plasmid DNA replication. AB - Lambda plasmid DNA replication is inhibited in amino acid-starved wild type Escherichia coli strains (stringent response) but not in amino acid-starved relA mutants (relaxed response). This replication is perpetuated by the replication complex containing the lambda O protein (which is protected from proteases by other elements of the complex) and inherited by one of two daughter copies after a replication round. Since a fraction of stable lambda O protein was observed in relA- and relA+ strains, and negative regulation by the lambda Cro repressor does not seem to be important in the stringent or relaxed response of lambda plasmid replication to amino acid starvation, the inhibition of lambda plasmid replication in amino acid-starved wild type strains was investigated. lambda plasmids were unable to replicate in amino acid-starved relA- bacteria treated with rifampicin. Moreover, transcription from pR, which produces mRNA for replication protein synthesis and serves as transcriptional activation of ori lambda, was significantly decreased during the stringent response as well as in non-starved cells containing increased levels of ppGpp. However, it was little or totally not affected by the relaxed response. The replacement of pR with plac (which is known to be uninhibited by ppGpp) in a lambda plasmid resulted in its DNA replication during relaxed and stringent responses as well as during overproduction of ppGpp in unstarved bacteria. We conclude that ppGpp-mediated inhibition of transcriptional activation of ori lambda is responsible for inhibition of lambda plasmid DNA replication in amino acid-starved wild type strains.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7988575 TI - A precursor terminal protein-trinucleotide intermediate during initiation of adenovirus DNA replication: regeneration of molecular ends in vitro by a jumping back mechanism. AB - The adenovirus type 5 origin sequence starts with 3' GTAGTA. Initiation of replication occurs by a protein priming mechanism in which the viral precursor terminal protein (pTP) is covalently linked to the first nucleotide of the nascent chain, a dCMP residue. This suggests that a pTP-dCMP (pTP-C) complex functions as an initiation intermediate. Employing a reconstituted replication system and both synthetic oligonucleotides and the natural TP-DNA as templates, we show that pTP-CAT rather than pTP-C is an intermediate in initiation. By replicating oligonucleotide templates mutated at different positions and analyzing the product lengths, we observed that the GTA at positions 4-6, rather than 1-3, are used as a template for pTP-CAT formation. Moreover, deletions of one or two nucleotides at the molecular ends were regenerated upon in vitro replication. Our results support a model in which the pTP-CAT intermediate, synthesized opposite to positions 4-6, jumps back to position 1 of the template to start elongation. In order to permit elongation, some base pairing between pTP CAT and template residues 1-3 is required. This jumping-back mechanism ensures the integrity of terminal sequences during replication of the linear genome. PMID- 7988576 TI - Molecular mechanism for the operation of nitrogen control in cyanobacteria. PMID- 7988577 TI - Epidural diamorphine infusions with and without 0.167% bupivacaine for post operative analgesia. AB - Forty patients who underwent upper or mid-abdominal surgery were randomly allocated to receive a post-operative epidural infusion of 0.083 mg ml-1 of diamorphine in either 0.167% bupivacaine or 0.9% NaCl solution. The nursing staff, who were unaware of which solution was being infused, managed the patients' pain according to a standardized scheme. They adjusted the epidural infusion rates to 3, 5 or 7 ml h-1 according to the patient's hourly reports of pain on a four point verbal rating scale (none, mild, moderate or severe), aiming to use the lowest allowed infusion rate to prevent or reduce any pain that was more than mild. Additional analgesia was given as diclofenac 75 mg intramuscularly if the patients report moderate pain while on the highest infusion rate. The nurses were instructed to summon anaesthetic help if pain relief was still unsatisfactory after diclofenac, but this was never necessary. Diclofenac was needed by six patients receiving diamorphine in saline and one receiving diamorphine in bupivacaine (P < 0.05). The range of average hourly epidural infusion rates was constrained by design to between 3 and 7 ml h-1 but the median of these values was 5 ml h-1 in the diamorphine-saline group and 3.35 ml h-1 in the diamorphine-bupivacaine group (P < 0.02). In patients receiving diamorphine in saline, a median of 6 (range 0-16) of the 24 h reports were of more than mild pain, whereas in the diamorphine-bupivacaine group, the corresponding figures were 2 (range 0-13) (P < 0.02)).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7988578 TI - Myocardial depressant effect of nitrous oxide after valve surgery. AB - We have studied the cardiovascular effects of 50% nitrous oxide after cardiopulmonary bypass in 14 patients undergoing valve surgery. All patients received morphine as the principal anaesthetic. Nitrous oxide administration for 5 min caused a decrease in mean arterial pressure from 82 +/- 10 to 71 +/- 12.7 mmHg (P < 0.001), cardiac index (2.8 +/- 0.5 to 2.4 +/- 0.5 litres min-1 m-2, P < 0.01), heart rate (104 +/- 17 to 99 +/- 18 beats min-1, P < 0.05), left ventricular stroke work index (29.4 +/- 8.1 to 22 +/- 8.7 gm-m beat-1 mm-1, P < 0.001), stroke volume (45.3 +/- 11.6 to 40 +/- 12.8 ml beat-1, P < 0.05) and an increase in pulmonary vascular resistance from 106.4 +/- 53.9 to 143.9 +/- 81.0 dynes s cm-5 (P < 0.01) and right atrial pressure (1.42 +/- 2.09 to 1.71 +/- 2.21 mmHg, P < 0.05). There was no change in systemic vascular resistance. When nitrous oxide was discontinued all the parameters started to recover within 3 min. Mean arterial pressure returned to control value in 5 min, but cardiac index and pulmonary vascular resistance returned to control value in 10 min. Our results suggest a direct myocardial depression and that the use of nitrous oxide is not recommended immediately after valve surgery and cardiopulmonary bypass. PMID- 7988579 TI - Propofol and methohexitone anaesthesia: effects on the profile of mood state. AB - The influence on mood of anaesthesia by infusion with propofol or methohexitone was evaluated in 80 female patients assessed with the Profile of Mood State preoperatively and at 30 min, 1, 2 and 4 h after anaesthesia. Patients given propofol were more elated and continuously less anxious than those given methohexitone from 1 to 4 h after anaesthesia (54.3, SEM 1.1 vs. 50.7 SEM 1.2). They also felt more agreeable after 2 h (45.4 SEM 1.4 vs. 48.4 SEM 1.2). All patients felt more tired and more confused post-operatively than pre-operatively. Propofol has different and more favourable influences on the post-operative mood state than does methohexitone. PMID- 7988580 TI - Metabolic and subjective responses to oral diazepam and midazolam. AB - Diazepam premedication decreases the overall metabolic rate and oxygen consumption. Whether its properties are shared by midazolam is not known. In this study, eight healthy male volunteers were given oral diazepam (10 mg), midazolam (15 mg) and placebo in a random double-blind cross-over fashion. Metabolic responses were measured using an indirect calorimetry device. Subjective responses were measured using a visual analogue scale. Plasma concentrations of diazepam, midazolam and desmethyldiazepam were analysed and correlated to changes in metabolic and subjective responses. When compared to placebo, both diazepam and midazolam significantly decreased oxygen consumption (P < 0.01 in pairwise comparisons) and energy expenditure (P < 0.01 in pairwise comparisons). While there was a significant correlation between the plasma concentrations of diazepam and the changes in metabolic parameters, no such correlation was found with midazolam. Both diazepam and midazolam were subjectively more sedative than placebo (P < 0.05). There was no significant difference between the sedative effects of diazepam and midazolam, but diazepam was subjectively better tolerated than midazolam. These results indicate that both diazepam and midazolam, in addition to their CNS effects, significantly decrease the overall metabolic rate and oxygen consumption in healthy volunteers. PMID- 7988581 TI - Do barbiturates and their solutions suppress FMLP-induced neutrophil chemiluminescence? AB - The dose-response relationship of four commercially available barbiturates (methohexitone, pentobarbitone, phenobarbitone and thiopentone) and of their drug free solutions on the production of oxygen radicals by neutrophils were tested by N-formylmethionyl-leucyl-phenylalanine (FMLP)-induced granulocyte chemiluminescence and in a cell-free chemiluminescence system. Methohexitone had no effect on neutrophil chemiluminescence. Pentobarbitone, phenobarbitone and thiopentone dose-dependently decreased FMLP-induced chemiluminescence and cell free chemiluminescence. Suppression of neutrophil chemiluminescence by pentobarbitone and phenobarbitone was due to effects of the drug-free solutions and an osmolality greater than 360 mosmol kg-1. Only thiopentone suppressed granulocyte chemiluminescence drug-specifically. The physicochemical properties of commercially available barbiturate preparations and their solutions, as well as free radical scavenging capacity, have to be considered if these preparations are used to evaluate drug-specific effects on the production of oxygen radicals by neutrophils. PMID- 7988582 TI - Global and regional haemodynamic effects of urapidil in conscious dogs with chronic coronary artery occlusion. AB - The haemodynamic effects of urapidil, an alpha 1-antagonist with central serotoninergic properties, were studied in an experimental canine model of chronic ischaemic heart disease. Global and regional haemodynamic recordings were made in conscious dogs with ameroid-induced single vessel coronary artery occlusion. Three intravenous bolus-infusion doses of urapidil (0.1 mg kg-1 + 0.3 mg min-1; 0.5 mg kg-1 + 1.5 mg min-1; 2.5 mg kg-1 + 7.5 mg min-1) were given on separate occasions in 12 animals. Regional blood flows were measured with radioactively labelled tracer microspheres. The effects of urapidil and dipyridamole, a powerful arteriolar vasodilator, on regional myocardial blood flow distribution to normal and collateral-dependent myocardium were compared. Urapidil caused a dose-dependent reduction of arterial blood pressure. There was moderate tachycardia and decreased left atrial filling pressures at the higher doses. Urapidil was a much weaker coronary vasodilator than dipyridamole. Dipyridamole caused maldistribution of intercoronary and transmural flows (endo to-epicardial flow ratio in collateral-dependent regions from 1.35 +/- 0.07 to 0.7 +/- 0.13 and flow ratio between collateral-dependent and normal regions from 1.09 +/- 0.03 to 0.57 +/- 0.14). Urapidil preserved blood flow to both regions. Urapidil did not affect systolic wall thickening fraction in normal or ischaemic regions of the heart. Renal (+16%) and splanchnic perfusion (+45%) increased during urapidil infusion. Urapidil preserves myocardial function and perfusion and increases renal and intestinal blood flow in dogs with chronically ischaemic hearts. PMID- 7988583 TI - Preferential channelling of anaesthetic solution injected within the perivascular axillary sheath. AB - Preferential channelling of anaesthetic solution injected into the perivascular axillary sheath was investigated in 40 patients undergoing elective orthopaedic upper-limb surgery. Three needles, with different approaches and inclinations, were inserted near the three main terminal branches of the brachial plexus using an axillary approach. Separate boluses of anaesthetic solution (12 ml of a mixture of equal parts of 0.5% bupivacaine with 1:200,000 adrenaline and 2% lignocaine) were injected in random order through each needle, and back flow through the other two needles was noted. Back flow was observed, mainly in the needle nearest to the radial nerve during injection of the anaesthetic solution in the superior and inferior aspects of the brachial artery, and in the needle close to the ulnar nerve when the injection was performed posterior to the artery, near the radial nerve. These results could be related to the trapping of anaesthetic solution in unconnected compartments and to the slope of the needle injecting the anaesthetic solution which spreads preferentially along a gradient following the needle shaft direction. PMID- 7988584 TI - Airway management in dental anaesthesia. AB - Ninety patients were allocated randomly to three groups for airway maintenance during paediatric outpatient dental extraction: laryngeal mask airway, nasal mask with nasopharyngeal airway, or nasal mask alone. Surgical access was better with the laryngeal mask. Airway maintenance was easier with the laryngeal mask than the nasopharyngeal airway, and both were better than nasal mask alone. No patient became hypoxic with the laryngeal mask, five patients became hypoxic with the nasal mask and two with the nasopharyngeal airway at corresponding periods, although the differences were not statistically significant. The laryngeal mask airway is recommended for paediatric outpatient dental anaesthesia. PMID- 7988586 TI - How noisy are anaesthesia and intensive care medicine? Quantification of the patients' stress. AB - The minimum and maximum sound pressure levels (Lmin, Lmax) were measured, and the energy equivalent sound pressure level (Leq) and the impulse rated Leq (LAlm) were ascertained in the surgical intensive care unit and the anaesthetic and recovery room. Frequency analyses were also made of the noise from various pieces of equipment. The LAlm was never below 60 dB(A)--the wake-up threshold in man- comprising strong narrow-band impulses with Lmax more than 100 dB(A) primarily from instrument alarms. When several instruments were alerted at the same time, a broad-band noise resulted which was based on their various spectral peaks. Whilst the maximum sound level of the technical equipment was high, it was surpassed by avoidable background noise caused by the staff (e.g. falling bucket lid: 94.7 dB(A)). No relationship was found between acoustic parameters and intended type of anaesthesia or surgery. Sound level was low in dangerous situations and high during routine work. PMID- 7988585 TI - Double burst stimulation with submaximal current. AB - The present study evaluated responses to double burst stimulation (DBS) at supramaximal and submaximal currents in 30 adult patients. Usually, DBS is applied with supramaximal stimulation, but this may be quite uncomfortable for the awake patient. Therefore, the authors investigated whether it is possible to obtain an accurate assessment of significant residual neuromuscular blockade if the stimulus current is reduced to 30 mA. In all patients, neuromuscular response to DBS three three (DBS3.3), DBS three two (DBS3.2) and train-of-four (TOF) stimulation at supramaximal and/or submaximal currents was recorded using a mechanomyograph, and the ratios of the fourth to the first twitch (T4/T1) induced by TOF stimulation at supramaximal current, and the height of the second response to the first (D2/D1) induced by DBS at 30 mA and supramaximal current were calculated. The relations between control T4/T1 ratios determined by supramaximal TOF stimulation and D2/D1 ratios determined by supramaximal DBS3.3 and submaximal DBS3.3 were Y = 0.99X + 0.08 and Y = 1.01X + 0.04, respectively, and there was no statistical difference between the two regression lines. The same relation between T4/T1 ratios and D2/D1 ratios by DBS3.2 were Y = 0.69X + 0.05 and Y = 0.72X + 0.02, respectively, and there was no significant difference. It is concluded that evaluation of the response to DBS at 30 mA has the same reliability as evaluation with supramaximal current. PMID- 7988587 TI - A patient's experience of a new post-operative patient-controlled analgesic technique. AB - A patient underwent major spinal surgery, twice within a 3 week period. On the first occasion his post-operative pain was managed by conventional morphine patient-controlled analgesia (PCA). After the second procedure his pain was managed by a patient-controlled computer-assisted titration of alfentanil. This provided the opportunity to compare the efficacy of these two drug regimens in the same subject. The results showed comparable quality of analgesia and sedation and similar effects on respiration. However, the patient expressed a preference for morphine PCA. PMID- 7988588 TI - One year's experience with an acute pain service in a Spanish University Clinic hospital. AB - We describe the experience of the acute pain service of the University Hospital of Galicia, Spain since its inception. We have treated 1214 patients using either patient-controlled analgesia (PCA) with morphine (72%), or patient-controlled epidural analgesia with fentanyl + bupivacaine (22%). Three hundred and five patients had minor complications, mainly pruritus (35%) in patients with patient controlled epidural analgesia. Three (0.33%) patients using PCA had respiratory depression treated with naloxone; no patient with patient-controlled epidural analgesia had respiratory depression. In our experience the creation of an acute pain service and the associated development of pain-treatment protocols and the training of hospital personnel produced excellent results. PMID- 7988589 TI - Anaesthesia for electroconvulsive therapy: use of propofol revisited. AB - In three clinically depressed patients undergoing repeated electroconvulsive therapy (ECT) with either propofol or methohexitone, dose-dependent decreases in the duration of motor and EEG seizure activity were noted. Use of a 'minimally' hypnotic dose of propofol (0.75-1.0 mg kg-1) was associated with a seizure duration which was comparable to standard hypnotic doses of methohexitone. We conclude that doses of propofol < 1.5 mg kg-1 are associated with a clinically acceptable duration of EEG seizure activity (> 30 s) during ECT. PMID- 7988590 TI - The Belgian evolution concerning the management of intensive care units. PMID- 7988591 TI - Blood pressure responses in Japanese and Swedish children in the supine and standing position. AB - We investigated the cardiovascular responses to active standing in Swedish and Japanese pre-pubertal children using non-invasive continuous beat-to-beat finger blood pressure (BP) monitoring. Seventy-eight Swedish (7-12 years) and 53 Japanese children (6-12 years) were examined. There were no significant differences in body weight or height between the two groups (total group). Finger blood pressure and heart rate were continuously recorded in the supine position and during standing. Supine BP was significantly higher in Swedish compared to Japanese children (115/65 vs 98/50 mmHg, P < 0.001), and Swedish children showed a significantly larger initial BP drop upon rising (-28/15 vs - 14/ -10 mmHg, P < 0.05) and a larger increment of heart rate (39 +/- 10 vs 29 +/- 8 beats. min-1, P < 0.05). There were, however, no differences in the blood pressure and heart rate changes in the following steady state period (2-3 min) between the two groups. These results suggest that Swedish pre-pubertal children have a higher basal blood pressure and enhanced cardiovascular autonomic responses, such as pronounced baroreflex receptor sensitivity and vasoconstrictor mechanisms. These differences in the two cohorts were not related to body dimensions or degree of maturation, indicating that autonomic functions in the cardiovascular system largely depend on genetic factors and environmental variables. PMID- 7988592 TI - Association of risk factors and body iron status to carotid atherosclerosis in middle-aged eastern Finnish men. AB - High body iron stores have been proposed as a risk factor for advanced atherosclerosis. We investigated the prevalence of early atherosclerotic changes, and their relation to conventional CHD risk factors and body iron status. A cross sectional study was carried out in 206 men aged 50 to 60 years (6% random population sample). Intima-media thickness (IMT) of the carotid artery was evaluated with high-resolution B-mode ultrasonography. Statistical analyses were performed separately for men with and without cardiovascular disease (CVD). Among all the study participants, 6.6% had IMT > 1.3 mm in the common carotid artery, whereas 53.8% had IMT > 1.5 mm in the carotid bifurcation. Respective values were 4.8% and 46.8% for those without CVD, and 8.5% and 62.2% for those with CVD. Mean IMT in the carotid bifurcation, the predilection site for atherosclerosis, was 1.85 mm (95% CI 1.72; 1.98) in the men with CVD, as compared to 1.65 mm (95% CI 1.56; 1.73) in the men free of CVD. Serum LDL cholesterol (beta = 0.26), saturated fat intake (beta = 0.20), blood haemoglobin (beta = -0.29), systolic blood pressure (beta = 0.21) and smoking (beta = 0.19), jointly explained 23% of the variance in the carotid bifurcation IMT in the men without CVD. Neither serum ferritin, transferrin nor dietary iron levels were associated with carotid bifurcation atherosclerosis. On the other hand, in the men with CVD, age (beta = 0.34) and physical activity (beta = -0.25) jointly explained 16.5% of the IMT variance in the carotid bifurcation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7988593 TI - Coronary risk factors and a 20-year incidence of coronary heart disease and mortality in a Mediterranean industrial population. The Manresa Study, Spain. AB - The association between coronary risk factors measured at entry and 20-year coronary heart disease (CHD) incidence and mortality was studied in an industrial cohort of 1059 men aged 30 to 59 years and free of CHD in 1968, in Spain. Myocardial infarction and fatal CHD cases were diagnosed according to recognized criteria. Mean serum cholesterol was 223.3 mg.dl-1 and 67% of men were current smokers. Rates of CHD incidence, CHD mortality and all-causes mortality, per 10(5) persons-year of observation, were 476, 194 and 617, respectively. Age, serum cholesterol, plasma glucose, cigarettes smoked and systolic blood pressure (SBP) contributed to the risk of CHD incidence. The first four variables predicted CHD death risk. All-causes death risk was positively associated with age, plasma glucose and SBP levels. Results are consistent with prior reported low CHD mortality and morbidity rates in the Mediterranean area, and confirm the importance of coronary risk factors in this low-risk population. PMID- 7988594 TI - Characteristic abnormal findings of ambulatory blood pressure indicative of hypertensive target organ complications. AB - To study the correlation between ambulatory blood pressure and target organ complications of hypertension, ambulatory blood pressure monitoring was performed on 290 patients with mild to moderate essential hypertension before treatment. Their target organ complications of hypertension were assessed by ECG, chest X ray, urinalysis and an eye-fundus examination. An average ambulatory diastolic blood pressure value greater than the casual diastolic blood pressure was found in 35% of subjects with ECG evidence of left ventricular hypertrophy (LVH) and 5.2% of subjects without (P < 0.001); in 36.5% of patients with chest roentgenographic evidence of LVH and 8.4% of patients without (P < 0.0001); in 38.5% of patients with proteinuria and 11% of patients without (P < 0.0001); and in 27.1% of subjects with retinopathy and 10.7% of subjects without (P < 0.01). A similar result was observed for the systolic blood pressure. A reversed circadian pattern of ambulatory diastolic blood pressure was observed in 32.5% of patients with ECG evidence of LVH and 12.9% without (P < 0.0001); in 28.8% of patients with chest roentgenographic evidence of LVH and 16% without (P < 0.05); in 26.9% of subjects with proteinuria and 17.4% without (P < 0.05); in 37.5% of patients with retinopathy and 14.5% without (P < 0.0001). A similar result was also demonstrated for ambulatory systolic blood pressure. There was a close relationship between the blood pressure load and hypertensive target organ complications in terms of LVH and proteinuria, and between significant nocturnal reduction of ambulatory systolic blood pressure and LVH.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7988596 TI - Coronary angioplasty in high risk patients with percutaneous cardiopulmonary support. AB - Cardiopulmonary Support (CPS) was employed electively in 13 patients during high risk percutaneous transluminal coronary angioplasty (PTCA) in accordance with a selection criteria, which included at least two of the following; (i) left ventricular ejection fraction of less than 35%, (ii) target vessel(s) supplying more than 50% of the viable myocardium, and (iii) patients refused coronary bypass surgery. The mean age of the patients was 56.8 +/- 10.7 years (range 39 77). PTCA was attempted in a total of 35 lesions in 12 patients; 29 lesions were successfully dilated (technical success rate of 82.9%). On average, 2.7 lesions were attempted in each patient, and 2.2 lesions were successfully dilated per patient. In one patient the procedure was abandoned due to dissection of the iliac artery during cannulation. One patient died of a large pulmonary embolism 72 h after the procedure. All the surviving 11 patients who had successful PTCA on CPS showed symptomatic improvement during a mean follow-up period of 18.5 +/- 4.3 months (range 11 to 24 months). The commonest complication encountered following the CPS-assisted PTCA was local haematoma (nine of 13 patients), but all patients required transfusion due to significant periprocedural blood loss. Our early experience suggests that CPS enhances the safety of undertaking PTCA in high risk patients. PMID- 7988595 TI - Improvement in left ventricular dysfunction after aortic reimplantation in 11 consecutive paediatric patients with anomalous origin of the left coronary artery from the pulmonary artery. Early results of a serial echocardiographic follow-up. AB - To study the potential for recovery of left ventricular function in patients with anomalous origin of the left coronary artery from the pulmonary artery (ALCAPA) after aortic reimplantation, serial two-dimensional echocardiographic examinations were performed before and up to 9 months after operation in 11 consecutive paediatric patients (group 1: six infants; group 2: five children above the age of 1 year). End-diastolic volume (EDV), end-systolic volume (ESV), stroke volume (SV), ejection fraction (EF), myocardial volume (MV), ratio of myocardial volume/end-diastolic volume (MVI), and regional wall motion of the left ventricle (LV) were studied. Pre-operatively, mean LVEDV was 339% of normal in group 1 and 289% in group 2 (P < 0.001); mean LVMV was about twice the normal value in both groups (P < 0.001); LVMVI was 0.79 +/- 0.23 in group 1 and 0.83 +/- 0.3 in group 2; LVEF was 28 +/- 10% in group 1 and 46 +/- 18% in group 2; regional wall motion was normal in two group 2 patients, the other showed uniform reduction in segmental shortening fraction. Postoperatively, mean LVEDV tended to become normal after 2 weeks in group 1 and after 3 months in group 2. In both groups mean LVEF reached the normal range after 3 months; LVMV as well as LVMVI normalized after 9 months. Three months after the operation, all infants had a nearly normal pattern of regional wall motion, while in three group 2 children a residual reduced shortening fraction could be observed in anterior or lateral segments.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7988597 TI - Left ventricular shape changes induced by aneurysmectomy with endoventricular circular patch plasty reconstruction. AB - Aneurysmectomy with left ventricular (LV) patch plasty reconstruction for anterior post-infarction LV aneurysm is usually followed by favourable haemodynamic results. The aim of this work was to describe the changes in LV shape induced by the intervention and to correlate them to the pre-operative data and to the surgical results. Twenty-two patients submitted to aneurysmectomy with this technique underwent a haemodynamic study before and 10-15 days after the intervention. Segmental wall motion was studied by the centreline method. LV shape was analysed by calculating the regional curvature of angiographic outlines (RAO 30 degrees projection). Results showed an improvement in LV pump function in 17 patients, which appeared mainly due to increased systolic shortening of the inferior wall. The intervention-induced modifications of LV geometry were characterized by: (1) marked reduction in end-diastolic volume, (2) shift of the angiographic apex counterclockwise, towards the aortic corner, (3) disappearance of the rim with negative curvature corresponding to the infero-apical border of the aneurysm, where the inferior wall resumed a normal outward convexity. No significant difference was found between the pre-operative haemodynamic data of patients who improved after surgery and those who did not. The presence of a rim of negative curvature at the infero-apical border of the aneurysm was the only pre-operative sign with a predictive value for the surgical outcome. PMID- 7988598 TI - Determination of left ventricular volume by two-dimensional echocardiography: comparison with magnetic resonance imaging. AB - Left ventricular volume was determined in 12 healthy volunteers using a newly developed two-dimensional echocardiographic delineation method. The results were compared with those of magnetic resonance imaging, which served as the method of reference. Left ventricular end-diastolic volume was 123 +/- 12 ml, echocardiographically defined, and 121 +/- 12 ml calculated with magnetic resonance imaging. End-systolic volume was 41 +/- 7 ml on echocardiography and 37 +/- 6 ml on magnetic resonance imaging. Left ventricular ejection fraction was 67 +/- 4%, echocardiographically defined, and 70 +/- 5%, calculated with magnetic resonance imaging. There was no statistical difference for any of the measured parameters. Interstudy and inter-observer variability was minimal. In conclusion, in healthy volunteers left ventricular volume was accurately defined, using this newly developed two-dimensional echocardiographic delineation method. During endocardial delineation a dynamic display is continuously available on a second window, allowing precise visual edge-detection. Moreover, corrections can be made easily and quickly. These two advantages enhance the accuracy of the method, even in cases of poor echogenicity. PMID- 7988599 TI - Assessment of chronic tricuspid regurgitation by colour Doppler echocardiography: a comparison with angiography in the catheterization room. AB - Colour Doppler echocardiographic (CDE) assessment of tricuspid regurgitation (TR) has been limited by the lack of an accepted model against which it can be compared. Angiography is said to be inadequate because catheter placement across the tricuspid valve could induce artifactual TR. Thirty-five consecutive patients with left-sided valvulopathy and recent heart failure were studied. Angiography was validated by CDE, which demonstrated that catheter placement across the tricuspid valve did not increase the size of the regurgitant jet in the first 30 cases. All the patients were studied with CDE immediately before performing the angiography in order to compare the findings of both techniques. From all the CDE parameters measured among the angiographic groups, the jet area overlapped the least (P = 0.024). The diameters of the right cardiac chambers were larger in angiographically severe cases (P = < 0.003 to 0.041), and a scale of severity that combined jet area and right atrium area showed an excellent correlation with angiography (r = 0.924; P < 0.001). Furthermore, maximal instant systolic gradients between the right cavities, estimated by catheterization, were lower in severe cases (P = 0.038). Assessment of these gradients by continuous Doppler can enhance recognition of severe TR. The analysis of jet area, right atrium area and regurgitant gradient by CDE can provide excellent assessment of TR. PMID- 7988600 TI - Value of oesophageal pacing in evaluation of atrial arrhythmias. AB - The study of 'atrial vulnerability' is often clinically indicated but it requires the use of invasive intracardiac stimulation. The purpose of the study was to assess the use of oesophageal pacing in the evaluation of atrial tachyarrhythmias (ATA). Fifty-five patients with documented ATA (group I) and 60 without (group II) were studied. The protocol of oesophageal pacing consisted of atrial pacing up to the second-degree AV block and programmed stimulation in the control state and after isoproterenol infusion. ATA was induced in 47 group I patients (85%) either in the control state (n = 27) or during isoproterenol infusion (n = 20) and in three group II patients (5%). There was no other electrophysiological abnormality. The presence of underlying heart disease did not precipitate ATA in group II. In conclusion, because of its good sensitivity (85%) and specificity (95%) transoesophageal pacing could be used to evaluate atrial arrhythmias. PMID- 7988601 TI - Prediction of mortality in mild to moderately symptomatic patients with left ventricular dysfunction. The role of the New York Heart Association classification, cardiopulmonary exercise testing, two-dimensional echocardiography and Holter monitoring. AB - In order to investigate the value of peak oxygen consumption (peak VO2) in predicting mortality in mild to moderately symptomatic patients with left ventricular dysfunction, we studied 103 NYHA II/III class patients with a left ventricular ejection fraction (LVEF) < or = 40%. Heart failure was due to coronary artery disease (CAD) in 39 patients, idiopathic dilated cardiomyopathy in 54, hypertension in eight and surgically corrected valvular disease in two. The following variables were analysed: age, cause of heart failure (CAD vs no CAD), NYHA class, peak VO2, LVEF, left ventricular end-systolic volume index (LVESVI), ventricular tachycardia (VT) on Holter monitoring and the use of antiarrhythmic drugs. Statistical analysis was performed by Cox's proportional hazards regression model. During a mean follow-up period of 20 months, there were 25 deaths. The estimated cumulative probabilities of survival were 88%, 73% and 58% at 1, 2 and 3 years, respectively. Cox's model identified CAD (P = 0.01), NYHA III class (P = 0.04) and LVEF (P = 0.02) as independent, statistically significant predictors of mortality. Peak VO2 had only a marginal statistical significance (P = 0.07). Age, LVESVI, VT on Holter monitoring and use of antiarrhythmic drugs were not related to mortality. These data can be important in patient clinical management and clinical trial design. PMID- 7988602 TI - Altered left ventricular diastolic function post-atrial pacing in coronary artery disease and left ventricular hypertrophy: further insights by pulmonary venous flow analysis. AB - Left ventricular filling dynamics during acute pacing-induced myocardial ischaemia were assessed using transoesophageal atrial pacing and simultaneous Doppler measurements of pulmonary venous and mitral flow. All patients (10 with CAD and 12 with left ventricular hypertrophy due to hypertrophic cardiomyopathy; HCM) were in sinus rhythm and patients with mitral insufficiency were excluded. Data were compared with those of a control group (n = 10). Measurements were obtained at baseline (heart rate 84 +/- 14 beats.min-1) and immediately after atrial pacing via the same transoesophageal echocardiography (TEE) probe after stepwise increase of the pacing rate to 133 +/- 12 beats.min-1. Heart rate immediately after pacing was 83 +/- 13 beats.min-1. Time velocity integrals (TVI) were calculated at baseline and after pacing for the following flows: early (E) and late (A) mitral flows, as well as antegrade systolic (S), diastolic (D) and retrograde diastolic (R) pulmonary venous flows. In the control group none of the flow parameters changed significantly after pacing compared with baseline data. In contrast, in CAD patients, the TVI of the E wave, the TVI E/A ratio as well as the pulmonary venous flow changed significantly after pacing (7.3 to 5.5 cm, P < 0.05, 1.7 to 1.1, P < 0.01 and 1.0 to 2.1 cm, P < 0.001, respectively). HCM patients also showed significant changes: TVI E/A ratio post-pacing decreased from 1.9 to 1.4 (P < 0.05), and the pulmonary venous reverse flow integral increased from 1.3 to 2.8 cm (P < 0.0001). Analysis of variance showed the TVI E/A ratio to be significantly dependent on pacing (P = 0.012). The pulmonary venous retrograde flow was found to be influenced by the presence of disease (P = 0.033 before and P = 0.0001 after pacing) and in all cases by pacing (before vs after pacing; P = 0.0001). Pacing resulted in significantly different changes in the TVI E/A ratio and the TVI of the retrograde pulmonary venous flow for CAD and HCM patients compared with those of control subjects. In patients with CAD and HCM, rapid atrial pacing results in a decreased early to late ventricular filling ratio because of impaired relaxation, despite presumably increased filling pressure. Retrograde pulmonary venous flow increased because of increased filling pressure and operating left ventricular stiffness. PMID- 7988603 TI - Reversal of ischaemic systolic and diastolic left ventricular dysfunction by successful coronary angioplasty in patients with non-Q wave anterior myocardial infarction. AB - The effect of PTCA on global and regional left ventricular systolic function, isovolumic relaxation, chamber and muscle stiffness were studied in 30 patients with angina pectoris, previous non-Q wave anterior myocardial infarction (AMI) and significant stenosis of the left anterior descending coronary artery (LAD). In 11 of the 30 patients the condition was stable, but it was unstable in 19. Left ventricular angiograms were obtained before and 4.85 +/- 3.67 months after PTCA. The RAO was in the 30 degree projection, with the silhouette of the left ventricle sliced into 90 regions; changes in left ventricular volume, pressure and anterior wall thickness during the full cardiac cycle, together with dp/dt were demonstrated. After PTCA, global ejection fraction increased from 68.77 +/- 5.96% to 76.57 +/- 3.18%, P < 0.001. Impaired contractility was found in 29/90 (32.2%) regions before PTCA and in 5/90 (5.6%) after PTCA, P < 0.001. The time constant of the isovolumic pressure fall decreased after PTCA (52.56 +/- 17.40 ms vs 39.61 +/- 11.26 ms, P < 0.01). Elastic chamber stiffness coefficient decreased (0.022 +/- 0.003 vs 0.008 +/- 0.004, P < 0.001) and peak rate of left ventricular filling increased (319.0 +/- 107.9 ml.min-1 vs 396.8 +/- 201.4 ml.min-1, P < 0.05) after PTCA. The muscle stiffness coefficient was within normal values before and did not change after PTCA. The study findings show that in patients with persistent angina pectoris after non-Q wave AMI, complex systolic and diastolic ischaemic dysfunction occurs. This dysfunction can be reversed after successful PTCA of LAD. PMID- 7988604 TI - Cardiac vagal hyperactivity in adolescent anorexia nervosa. AB - Adolescent anorexia nervosa, a psychiatric disease with high mortality, is often associated with bradycardia. We studied the vagal control of sinus node function in anorexic subjects, to investigate the mechanism of anorexic bradycardia. Cardiac vagal tone was determined in a group of 11 adolescent anorexic girls and in 11 age- and height-matched controls. Cardiac vagal tone in the anorexic patients was measured as the change in R-R interval in response to complete cholinergic blockade; in addition, non-invasive indices of cardiac vagal tone and baroreflex sensitivity were determined in both anorexic and control subjects. Cardiac vagal tone in anorexic subjects was 465 +/- 52 (SE) ms, about 30% higher than values reported for healthy subjects. Vagal tone values were directly related to percent weight loss (R = 0.69, P = 0.017). Non-invasive indices of both cardiac vagal activity and baroreflex sensitivity were significantly higher in the anorexic group as compared to controls; the percent increase of cardiac vagal tone, however, exceeded the increase of baroreflex sensitivity. Cardiac vagal hyperactivity significantly contributes to the bradycardia of anorexic subjects. The excess vagal activity is only partly explained by enhanced baroreflex sensitivity. PMID- 7988606 TI - Cardiac involvement in Ribbing's disease. AB - Cardiac involvement was assessed in 14 patients with Ribbing's disease, a rare hereditary sclerosing bone dysplasia. When compared to age-, sex- and blood pressure-matched controls, the patients with Ribbing's disease had significant alterations in left ventricular systolic and diastolic function and an impaired exercise tolerance. Supraventricular and ventricular arrhythmias also tended to be more frequent in these patients than in controls. In conclusion, Ribbing's disease, initially described as a skeletal disease only, also involves the cardiovascular system. Despite its rarity, the expression of the disease is easily followed and identification of the genetic defect could shed some new light on the pathophysiological mechanisms linking hypertension, myocardial hypertrophy and diastolic dysfunction. PMID- 7988605 TI - Thallium perfusion and myocardial hypertrophy in transplanted heart recipients with normal or near-normal coronary arteriograms. AB - In patients with hypertrophic cardiomyopathy or systemic hypertension, exercise thallium perfusion defects have been observed but without significant angiographic stenoses. Hypertension and myocardial hypertrophy are common in transplanted heart recipients, and the aim of this study was to determine if exercise thallium scintigraphy false-positives are frequent in transplanted heart recipients. Thirty-four transplanted heart recipients were evaluated by exercise thallium single emission computed tomography and subsequently had a normal or near normal coronary arteriogram. At the time of the exercise, the patients (28 men and six women) had a mean age of 48.9 +/- 12 years and 29 had been previously treated for systemic hypertension. The mean duration between transplantation and the exercise test was 31.6 +/- 13 months. In all patients left ventricular mass was obtained by echocardiography within 3 months of thallium 201 SPECT and was > or = 130 g.m-2 in nine males and > or = 110 g.m-2 in four females. M-mode septal + posterior end-diastolic thickness was > 23 mm in 14 patients, all of whom had been previously treated for systemic hypertension. These patients were older and endured a longer period during which the heart was kept cold but ischaemic before being grafted ('cold ischaemia') but a shorter exercise duration than patients without left ventricular hypertrophy. During exercise testing, 26 of 34 patients achieved at least 80% of their maximal predicted heart rate and two developed significant ECG changes.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7988607 TI - Effect of various antithrombotic regimens (aspirin, aspirin plus dipyridamole, anticoagulants) on the functional status of patients and grafts one year after coronary artery bypass grafting. AB - From 1987 until 1991 a large prospective randomized multicentre study was performed in The Netherlands, Germany and Switzerland entitled CABADAS (Prevention of Coronary Artery Bypass graft occlusion by Aspirin, Dipyridamole, and Acenocoumarol/Phenprocoumon Study). The aim of CABADAS was to evaluate the relative efficacy of (1) aspirin, (2) aspirin plus dipyridamole, and (3) oral anticoagulants in the prevention of vein graft occlusion during the first year after aortocoronary bypass surgery. No significant difference was observed in the incidence of graft occlusion among the three treatment groups. In a subgroup of 127 CABADAS patients, studied in the Academic Medical Centre in Amsterdam, the relationship between treatment and clinical status (i.e. symptoms of angina pectoris and exercise capacity) was assessed, and the relationship between treatment and functional status of the vein grafts was determined by means of thallium-201 exercise scintigraphy. There were no differences in symptoms among the three treatment groups in the 127 patients studied. There were no significant differences either among the treatment groups, as regards exercise capacity and the number or intensity of perfusion defects, in the 81 patients who underwent thallium-201 exercise scintigraphy. The three antithrombotic treatment regimens had a similar effect on the clinical status of patients and on the functional status of venous bypass grafts one year after coronary bypass surgery. This finding underscores the CABADAS results in that aspirin may be the preferred treatment option in patients following venous bypass surgery. PMID- 7988609 TI - The effect of subsequent myocardial damage on the expression of coxsackievirus B4 myocarditis and the development of ventricular aneurysms. AB - Coxsackievirus B (CB) 4 causes transmural myocarditis in suckling mice with ensuing development of focal ventricular thinning or aneurysms. We studied whether subsequent infection with another cardiotropic virus influences the expression of CB4 disease. CB4 infection was established in 2-day-old CD1 mice by intraperitoneal (IP) inoculation. Three weeks later, surviving animals were randomized to receive CB3 or saline IP. They were then killed over a 45-day period. CB4 neutralizing antibody (NA) titres were comparable in both groups (31 +/- 23 vs 37 +/- 19). CB3 NA were detected in CB3 infected animals only (72 +/- 86 versus 0). The incidence of myocarditis was comparable (67.4% vs 55.2%). The indices of histopathological changes (assessed according to a semiquantitative grading scale from 0-4) were greater among CB3 recipients on day 9 post CB3 challenge (1.38 +/- 0.43 vs 0.46 +/- 0.4, P < 0.001) and to a lesser extent, on day 13 (0.56 +/- 0.56 vs 0.19 +/- 0.38, P > 0.1). On days 30, and 45, these indices became similar in both groups. Focal thinning was noted on days 45 in 6/11 animals with CB4 infection alone and in 0/11 mice with subsequent CB3 infection (P = 0.006). These findings show that CB3 myocarditis can be expressed in mice with prior CB4 disease, that sequential infections do not lead to cumulative cardiac injury, and that subsequent CB3 infection suppresses the formation of CB4 induced ventricular aneurysms. PMID- 7988608 TI - Quality of life on enalapril after acute myocardial infarction. AB - Quality of life was assessed 4-6 months after an acute myocardial infarction in a randomized double-blind study of enalapril versus placebo. Quality of life was evaluated using the Nottingham Health Profile (NHP), the Physical Symptoms Distress Index (PSDI), the Work Performance Scale (WPS) and the Life Satisfaction Index (LSI). The study comprised 36 women (aged 46-85 years, mean 68) and 96 males (aged 39-81 years, mean 62). Quality of life did not differ significantly between patients treated with enalapril versus placebo. The scores were (enalapril vs placebo, mean +/- SE): average NHP 15.4 +/- 2.3 vs 17.1 +/- 2.3; PSDI 9.5 +/- 1.0 vs 10.8 +/- 0.9; WPS 19.8 +/- 2.0 vs 19.4 +/- 1.4; LSI 24.1 +/- 1.0 vs 22.5 +/- 1.4. Men reported a better quality of life than women on most assessments, and non-smokers and ex-smokers better than smokers. Patients with moderate or severe angina pectoris had a worse quality of life measured by PSDI and NHP than patients with minimal or no angina pectoris. Patients with congestive heart failure had a higher PSDI than those without (13.6 +/- 1.7 vs 9.4 +/- 0.7, P < 0.05), while no significant differences were observed in the NHP scores. In conclusion, quality of life was similar in enalapril and placebo treated patients after an acute myocardial infarction. However, it was reduced in patients with angina pectoris or heart failure and in those who continued smoking. PMID- 7988610 TI - Reactive thrombocytosis and stroke following cardiopulmonary bypass surgery: case report on three patients. AB - Reactive thrombocytosis following cardiopulmonary bypass surgery is generally considered to be a benign condition which is transient and does not require specific therapy. We describe three patients who developed stroke in association with reactive thrombocytosis in the late recovery period following cardiopulmonary bypass surgery. No evidence of embolic or cerebrovascular disease was detected in any patient. Analysis of a larger group of patients is required in order to determine whether reactive thrombocytosis may contribute to the pathogenesis of stroke in some patients following cardiopulmonary bypass surgery. PMID- 7988611 TI - Laser catheter ablation of atrial flutter and of atrioventricular nodal reentrant tachycardia in a single session. AB - This report describes an adolescent with refractory atrial flutter (AF) and atrioventricular (AV) nodal reentrant tachycardia who was cured by Nd: YAG, 1064 nm, laser application. Two impacts of 30 s each (power 30 W and irradiated spot diameter 2.0-2.5 mm), applied via a novel laser catheter system, abolished both AF and AV nodal reentrant tachycardia. The procedure was without complications or recurrent arrhythmias. PMID- 7988612 TI - Bilateral coronary ostial stenosis and aortic valvular disease after radiotherapy. PMID- 7988613 TI - Diet and reinfarction. PMID- 7988614 TI - Hypersensitivity reactions to streptokinase. PMID- 7988615 TI - Joint XIIth World Congress of Cardiology and XVIth Congress of the European Society of Cardiology. September 10-14, 1994, Berlin, Germany. Abstracts. PMID- 7988616 TI - 6th World Congress of Nuclear Medicine and Biology. October 23-28, 1994, Sydney, Australia. Abstracts. PMID- 7988617 TI - 4th Annual meeting of the German Society of Clinical Pharmacology and Therapy. Hannover, 14-17 September 1994. Abstracts. PMID- 7988619 TI - The effect of tacrine and lecithin in Alzheimer's disease. A population pharmacodynamic analysis of five clinical trials. AB - Tacrine, a cholinesterase inhibitor, has beneficial effects on cognition and global status in patients with Alzheimer's disease. These effects have been demonstrated in clinical trials by double-blind comparisons with placebo. Tacrine dosages have been studied in 5 protocols that used either enrichment or parallel designs. We have used a population pharmacodynamic model to describe the response to tacrine and placebo in the 3 trials that used the enrichment design. The time course of the response and its relation to tacrine dosage obtained from the enrichment design analysis were used to define the parallel design. The effects of tacrine on cognition and global status was estimated separately from each trial. Analysis of the 2 trials using the parallel design confirmed the predictions from the enrichment design. By combining the data from all 5 trials it was possible to show that tacrine potency was similar in all studies, but that the placebo response was different in some. The effect of tacrine was linearly proportional to dosage from 40 to 160 mg per day. One of the enrichment design trials included a sub-group treated with lecithin, a choline precursor. The potency of lecithin was equivalent to about 40 mg per day of tacrine. Using the combined data from all 5 trials it was possible to distinguish a responder population, approximately one-third of all patients, with a 4-fold greater effect compared with poor responders. Tacrine has beneficial effects on cognitive status in patients with Alzheimer's disease. Lecithin has a small additional benefit independent of tacrine.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7988620 TI - Transient neutropenia after intravenous injection of vindesine in patients with lung cancer. AB - We have found transient circulating neutropenia and pulmonary sequestration of neutrophils after the intravenous injection of vindesine, a microtubule disruptor. Experiment 1 Ten patients with lung cancer were given a bolus intravenous injection of 3 mg.m-2 vindesine (Fildesine(r)). In all patients, total leukocyte and neutrophil counts in the venous blood fell to 65% and 47% of baseline values respectively within 30 min, and returned to baseline values within 6 h. In contrast, the lymphocyte count was stable. Experiment 2 Male Wistar rats were given saline or 0.08 mg.kg-1 vindesine intravenously and were sacrificed after 30 min. Vindesine produced a 58% reduction in the neutrophil count in the systemic circulation and a threefold increase in the neutrophil/erythrocyte ratio in the pulmonary microvasculature. Experiment 3 We studied the effects of vindesine in vitro on neutrophils and lymphocytes isolated from the venous blood of healthy volunteers. Vindesine (10(-5)-10(-8) mol.l-1) reduced neutrophil deformability (filterability) and induced neutrophil polarization, with reversibility of both effects after washout. These effects of vindesine were completely inhibited by cytochalasin B, an actin filament disrupter. Vindesine did not stimulate the neutrophil functions of adherence to polystyrene tubes, chemotaxis, or superoxide anion generation. The filterability and morphology of lymphocytes were not altered by vindesine. Thus, we conclude that a bolus injection of vindesine produces pulmonary sequestration of neutrophils, which produces circulatory neutropenia, and that it is primarily mediated by a decrease in neutrophil deformability that occurs without activation of the cells. PMID- 7988618 TI - Complexes of metals other than platinum as antitumour agents. AB - The earliest reports on the therapeutic use of metals or metal-containing compounds in cancer and leukemia date from the sixteenth and nineteenth centuries. They were forgotten until the 1960s, when the anti-tumour activity of the inorganic complex cis-diammine-dichloroplatinum(II) (cisplatin) was discovered. This led to the development of other types of non-organic cytostatic drugs. Cisplatin has developed into one of the most frequently used and most effective cytostatic drugs for the treatment of solid carcinomas. Numerous other metal compounds containing platinum, other platinum metals, and even non-platinum metals were then shown to be effective against tumours in man and experimental tumours in animals. These compounds comprise main-group metallic compounds of gallium, germanium, tin, and bismuth, early-transition metal complexes of titanium, vanadium, niobium, molybdenum, and rhenium, and late-transition metal complexes of ruthenium, rhodium, iridium, platinum, copper, and gold. Several platnium complexes and four non-platnium-metal antitumour agents have so far entered early clinical trials. Gallium trinitrate and spirogermanium have already passed phase II clinical studies and have shown limited cytostatic activity against certain human carcinomas and lymphomas. The two early-transition metal complexes budotitane and titanocene dichloride have just reached the end of phase I clinical trials and have been found to have an unusual pattern of organ toxicity in man. Titanocene dichloride will soon enter phase II clinical studies. PMID- 7988621 TI - Non-lectin component in a fermented extract from Viscum album L. grown on pines induces proliferation of lymphocytes from healthy and allergic individuals in vitro. AB - Mistletoe preparations have been shown to express immunomodulatory properties. In order to evaluate the stimulatory potency of different mistletoe extracts, peripheral blood mononuclear cells (PBMC) from healthy and allergic/atopic individuals were exposed to aqueous or fermented extracts derived from Viscum album L. grown on apple trees (Mali-extracts) or on pines (Pini-extracts). None of them had received any mistletoe treatment. Iscador Pini was the only extract which strongly induced proliferation of PBMC in contrast to the other five preparations. On testing these extracts by Western blotting with anti-mistletoe lectin-1 (ML-1) antibody positive sera from mistletoe-treated patients, it became evident that Iscador Pini was almost devoid of lectins. The stimulatory potency of Iscador Pini for PBMC from three different groups was examined: PBMC from 35 normal controls (Group I), 23 patients with drug-induced adverse effects (Group II) and 16 individuals with allergic manifestations (Group III). Cells were exposed in 7-day cultures to the extract at concentrations between 1 and 10,000 micrograms/ml. PBMC from 63% of Group III individuals showed strong stimulation (SI varying from 6 to 97) in contrast to only 9% from Group I and 22% from Group II individuals. Anti-ML-1 antibodies were detected in 5% and anti-IP antibodies in 11% of subjects in the three groups. They were either of the IgA or IgM type but not of the IgG type. Our findings strongly imply that a non-lectin associated antigen from Iscador Pini is able to activate PBMC from healthy and allergic/atopic individuals, thereby demonstrating sensitization to probably highly conserved plant antigens. PMID- 7988622 TI - Comparison of the effects of dilevalol and propranolol on systemic and regional haemodynamics in healthy volunteers at rest and during exercise. AB - The effects of single oral doses of dilevalol 400 mg and propranolol 80 mg on systemic and regional haemodynamics at rest and after sub-maximal exercise, were compared, in a placebo-controlled, randomised, double-blind, crossover study in 6 healthy male volunteers. At rest, as compared to placebo, neither dilevalol nor propranolol significantly affected arterial pressure and heart rate but, whereas propranolol decreased cardiac output (-27% at 2 h) and tended to increase total peripheral resistance, dilevalol tended to increase cardiac output and decreased total peripheral resistance (-7% at 2 h). Neither dilevalol nor propranolol affected brachial artery diameter. Propranolol tended to decrease brachial artery flow (-20% at 2 h) and to increase brachial vascular resistance (+25% at 2 h), but dilevalol did not and the brachial irrigation ratios did not change. Neither of the drugs affected carotid haemodynamics or plasma atrial natriuretic factor. Both drugs tended to decrease plasma renin activity, and dilevalol (+82% at 2 h) increased norepinephrine more than propranolol (+19% at 2 h). After exercise, dilevalol and propranolol produced similar falls in the induced increases in arterial pressure, heart rate and cardiac output, and had the same effects on regional haemodynamics, plasma renin activity and atrial natriuretic factor. Finally, dilevalol greatly increased plasma norepinephrine. We conclude that the beta 2-adrenoceptor agonist activity of dilevalol was clearly expressed at rest, thus inducing vasodilation and counteracting the beta-adrenoceptor blockade induced negative chronotropic and inotropic effects. However, during sub-maximal exercise, only the beta-adrenoceptor antagonist activity of dilevalol was apparent. PMID- 7988623 TI - Azithromycin does not alter the effects of oral midazolam on human performance. AB - Since macrolide antibiotics inhibit the oxidative hepatic metabolism of various drugs, including midazolam, the present double blind studies were conducted to find out if azithromycin, a new macrolide of the azalide type, would inhibit the metabolism of midazolam and enhance the effects of midazolam on human performance. In Study I, 64 healthy medical students, divided in four parallel groups received placebo, midazolam (10 mg or 15 mg), and midazolam 10 mg combined with azithromycin (500 mg + 250 mg). In Study II, three males received oral midazolam 10 mg in combination with placebo, azithromycin or erythromycin 750 mg (as a positive control) in a cross-over trial. Objective and subjective tests were done before the intake of midazolam and 30 and 90 min after it, and venous blood was sampled for the assay of midazolam. In the placebo group in Study I, the mean numbers of letters cancelled (LC) at baseline, 30 min and 90 min were 21, 20 and 20, respectively, and the corresponding mean numbers of correct digit symbol substitutions (DSS) were 126, 137 and 140, indicating a practice effect. Midazolam 10 mg impaired these performances (21, 13 and 12 for LC, and 127, 113 and 111 for DSS). Either dose of midazolam produced clumsiness, mental slowness and poor subjective performance, midazolam 15 mg being slightly more active. The corresponding, scores in the azithromycin+midazolam group were 21, 16, 16 for LC, and 132, 121 and 119 for DSS, the only significant difference from placebo being the impairment of DSS at 90 min.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7988624 TI - The effect of hyperglycaemia on the absorption of glibenclamide in patients with non-insulin-dependent diabetes mellitus. AB - We have studied the absorption of glibenclamide 10 mg as a single morning dose in 7 patients with non-insulin-dependent diabetes mellitus, comparing normoglycaemic and hyperglycaemic states. The maximal glibenclamide plasma concentrations were significantly higher in the normoglycaemic than in the hyperglycaemic state (448 vs 228 mg.l-1) and these peak concentrations were attained faster in normoglycaemia than in hyperglycaemia (3.7 vs 5 h). We conclude that the absorption of glibenclamide in the two states is different. PMID- 7988625 TI - The effects of age and sex on the systemic availability and pharmacokinetics of transnasal butorphanol. AB - We have studied the effects of age and sex on the pharmacokinetics and the systemic availability of transnasal butorphanol in a randomized, two-way, cross over study of 48 subjects: young men and women, and elderly men and women. Each subject took a single 1 mg dose of intravenous and transnasal butorphanol tartrate on separate occasions with a one-week washout period. Blood samples were collected over 16 hours. Plasma butorphanol concentrations were determined using radioimmunoassay. The AUC of plasma butorphanol concentrations after an intravenous injection were higher in the elderly women than in the other groups. However, there were no significant differences in Cmax and AUC between the groups after transnasal administration. The mean systemic availability of transnasal butorphanol was about 70%, except for the elderly women (48%). After intravenous and transnasal administration, the half-life and mean residence time were greater in the elderly than the young. Clearance was lower in women than men. Apparent volume of distribution was higher for elderly men than the others. The age- and sex-related changes in the pharmacokinetics of transnasal butorphanol are not large enough to necessitate dosage differences. PMID- 7988627 TI - The effect of food on the interaction of ofloxacin with sucralfate in healthy volunteers. AB - We have studied the effect of food on the interaction of ofloxacin with sucralfate. Six healthy men took a single oral dose of ofloxacin (200 mg) on 4 occasions: alone after overnight fasting or after breakfast (non-fasting), and with sucralfate fasting or non-fasting. There were no significant differences in the plasma concentration-time profiles of ofloxacin after ofloxacin alone between fasting and non-fasting conditions. On the other hand, the peak plasma concentration and AUC of ofloxacin after co-administration with sucralfate while fasting fell by 70 and 61% compared with ofloxacin alone; the changes non-fasting were 39 and 31% respectively. The interaction of ofloxacin with sucralfate was markedly reduced by food, but still could not be disregarded. PMID- 7988626 TI - Cyclosporine pharmacokinetics in nephrotic and kidney-transplanted children. AB - The pharmacokinetic parameters of cyclosporine (CsA) were determined in 23 kidney transplant recipients and 19 children with nephrotic syndrome, after intravenous and oral administration. The mean bioavailability was 39%, blood clearance was 0.55 l.h-1.kg-1 and volume of distribution at steady-state was 2.77 l.kg-1. The absorption profile was monophasic (67%), biphasic (29%) or poor (4%). The maximum blood concentration of CsA was significantly higher in children with a monophasic profile than in children with a biphasic profile (550 vs 380 ng.ml-1). Blood clearance was significantly higher in the transplant recipients than in the patients with nephrotic syndrome (0.65 vs 0.43 l.h-1.kg-1. Although age, haematocrit, creatinine clearance, serum albumin and cholesterol differed between the two groups, only haematocrit and creatinine clearance were significantly (negatively) correlated with CsA clearance. PMID- 7988628 TI - No influence of ciprofloxacin on ethanol disposition. A pharmacokinetic pharmacodynamic interaction study. AB - The influence of pretreatment with a three day course of ciprofloxacin (500 mg twice daily) on a single oral dose of ethanol (30 g) was investigated in 12 healthy male volunteers in a double blind placebo controlled study. Pretreatment with ciprofloxacin was shown to have no significant effect on ethanol AUC (736 mg.l-1 h placebo; 734 mg.l-1 h ciprofloxacin), Cmax (466 mg.l-1 placebo; 483 mg.l 1 ciprofloxacin) tmax (0.6 h placebo; 0.5 h ciprofloxacin) or the elimination rate (134 mg.l-1 h-1 placebo; 133 mg.l-1 h-1 ciprofloxacin). The effect of ciprofloxacin on ethanol pharmacodynamics was measured by the use of psychomotor tests, such as the critical flicker fusion threshold, choice reaction time, pursuit rotor, tapping rate, digit symbol substitution and digit span. Subjective feelings of concentration, vigilance and relaxation were also measured using visual analogue scales. Pretreatment with ciprofloxacin was found to have no significant effect on any of these tests, compared to placebo. PMID- 7988629 TI - Conventional and controlled release diltiazem. Bioavailability in healthy volunteers and anti-anginal effects in combination with metoprolol in stable angina pectoris. AB - Diltiazem CR tablets 120 mg b.i.d. for 1 week were compared with plain tablets 60 mg q.i.d. in 13 healthy male volunteers in a study of pharmacokinetic variables. Their antianginal efficacy was also compared in 23 patients with stable angina pectoris who were already on metoprolol. Both studies were of randomised, cross over design, and the clinical study was double blind. The pharmacokinetic variables of the two formulations were very similar except for the longer tmax of 4.4 h for diltiazem CR in comparison to 2.9 h for the plain tablets. The mean relative bioavailability of diltiazem CR in comparison with plain tablets was 1.14. The clinical study showed that after four weeks on diltiazem CR 120 mg b.i.d. or diltiazem plain tablets 60 mg q.i.d. in addition to metoprolol, there were significant decreases in weekly anginal attacks from 11 to 5 attacks/week, the number of nitroglycerin tablets consumed from 6 to 3 tablets/week, and an increase in the maximum workload from 116 to 126 and 123 W for diltiazem CR and plain diltiazem tablets, respectively, as compared to placebo. Five of the patients were angina free during diltiazem treatment. No difference in anti anginal efficacy between the two preparations was seen. It was concluded that CR 120 mg b.i.d. appears bioequivalent to plain diltiazem tablets 60 mg q.i.d. PMID- 7988630 TI - Differences in the bioavailability of dihydrotachysterol preparations. AB - The bioavailability of four preparations containing dihydrotachysterol (DHT2) was tested in two separate trials with administration of single, oral doses of 1 mg per individual. The relative bioavailability of corresponding preparations (capsules vs capsules and oral solution vs oral solution) was tested in a randomised, cross-over pattern within the same group of volunteers. Two different groups of 24 healthy volunteers took part in each trial. Solution and capsule bioavailability was also compared inter-individually. A new sensitive HPLC-method (quantification limit 0.5 ng.ml-1) was used for the measurement of DHT2 concentration in serum. Three of the preparations tested had a similar bioavailability (mean AUC values of 195.5-223 ng.h.ml-1); the bioavailability of the fourth preparation (A.T.10 oral solution) was considerably lower (mean AUC value 111.5 ng.h.ml-1). The present dosage recommendations of all four preparations are identical. A new dosage recommendation is thus required for the oral solution with low bioavailability (A.T.10). PMID- 7988631 TI - Whole blood concentrations of mefloquine enantiomers in healthy Thai volunteers. AB - We studied the pharmacokinetics of the enantiomers of mefloquine in whole blood in healthy Thai volunteers after administration of a single oral dose of 750 mg of the racemic mixture. Mefloquine pharmacokinetics were stereoselective. The peak concentrations and areas under the curve of the (-) enantiomer were significantly higher than those of its antipode (0.79 versus 0.46 microgram.ml-1 and 402 versus 94 micrograms.h.ml-1). The half-lives of (-)MQ were significantly longer than those of (+)MQ (531 versus 206 h). No stereoselectivity was observed for tmax values. PMID- 7988632 TI - Methaemoglobinaemia produced by metoclopramide in an adult. PMID- 7988633 TI - S 14297, a novel selective ligand at cloned human dopamine D3 receptors, blocks 7 OH-DPAT-induced hypothermia in rats. AB - The selective dopamine D3 receptor agonist, 7-OH-DPAT ((+)-7-hydroxy-2-(di-n propylamino)tetralin) and the novel naphthofurane, S 14297 ((+)-[7-(N,N dipropylamino)-5,6,7,8-tetrahydro- naphtho(2,3b)dihydro,2,3-furane]), bound with high affinity and selectivity to recombinant, human dopamine D3 versus D2 receptors stably transfected into Chinese hamster ovary cells: Ki values = 2 versus 103 nM for 7-OH-DPAT and 13 versus 297 nM for S 14297. In contrast, the putative dopamine D3 receptor antagonist, AJ 76 (cis-(+)-5-methoxy-1-methyl-2-(n- propylamino)tetralin), displayed low affinity and selectivity for dopamine D3 versus D2 sites (70 versus 154 nM). 7-OH-DPAT (0.01-0.16 mg/kg s.c.) provoked hypothermia in rats, an action abolished by S 14297 (0.04-0.63 mg/kg s.c.) and, less potently, by AJ 76 (0.16-2.5 mg/kg s.c.). S 14297 (20.0 mg/kg s.c.) did not modify prolactin secretion. These data suggest that dopamine D3 receptors mediate hypothermia in the rat and that S 14297 acts as a selective antagonist at these sites. PMID- 7988634 TI - Acetylcholine receptor agonists stimulate [3H]taurine release from rat sympathetic ganglia. AB - The endogenous taurine content, and the uptake and release of [3H]taurine were examined using the rat superior cervical ganglion. Taurine was found to be one of the most abundant amino acids in the superior cervical ganglion, and the superior cervical ganglion took up [3H]taurine from the incubation medium. Carbachol stimulated the release of [3H]taurine in a concentration-dependent manner with an EC50 of 26 microM and maximal stimulation at 100 microM. The nicotinic receptor agonist 1,1-dimethyl-4-phenylpiperazinium stimulated release with the same potency but with greater efficacy than carbachol. The nicotinic receptor antagonist hexamethonium (1 mM) inhibited carbachol-stimulated release by 74%. (+/-)-Muscarine stimulated release with an EC50 of 8 microM but with a maximal effect of only 32% of that produced by 100 microM carbachol. Oxotremorine, another muscarinic receptor agonist, was ineffective, even at 1 mM. The muscarinic receptor antagonist atropine inhibited carbachol-stimulated release by 30% at 10 microM. These results show that [3H]taurine release from rat superior cervical ganglion can be stimulated by cholinergic receptor agonists. Release is mediated predominantly by a nicotinic receptor and partially by a muscarinic receptor. PMID- 7988635 TI - Intrathecal injection of cell-permeable analogs of cyclic 3',5'-guanosine monophosphate produces hyperalgesia in mice. AB - Several recent studies suggest that spinal cord levels of cyclic 3',5'-guanosine monophosphate (cGMP) may participate in the development of hyperalgesia. The purpose of this study was to directly evaluate whether cell permeable analogues of cGMP evoke a thermal hyperalgesia (using a hot-plate assay) when administered intrathecally in mice. Our results indicate that two cell permeable forms of cGMP evoke a dose dependent hyperalgesia when administered intrathecally in mice. Additionally, this hyperalgesia was selective since neither non-cell permeant cGMP nor guanosine had any effect on the latency of paw withdrawal when compared to the vehicle injected controls. These data indicate that cGMP is involved in the facilitation of thermal hyperalgesia at the level of the spinal cord. PMID- 7988636 TI - Conditioned place aversion produced by dopamine release inhibition. AB - CGS 10746B, a dopamine release inhibitor with properties similar to the atypical antipsychotic clozapine, was assessed as to its behavioral properties using spontaneous locomotor activity and the conditioned place preference test. Rats conditioned with interperitoneally administered doses of 1.25, 2.5, 5.0, 10.0, 20.0 or 30.0 mg/kg CGS 10746B showed a conditioned place aversion, whereas only doses of 5.0 mg/kg or greater suppressed locomotor activity. Results are discussed in terms of dopaminergic mediation of conditioned place preference and spontaneous locomotor activity and methodological concerns involved in employing the conditioned place preference test with drugs that produce opposing affective cues. PMID- 7988637 TI - Characterization of 5-hydroxytryptamine-induced depolarizations in rat isolated vagus nerve. AB - An additional component of the depolarization induced by 5-hydroxytryptamine (5 HT) in the rat isolated vagus nerve has recently been attributed to activation of 5-HT4 receptors. To confirm and extend this finding, extracellular recordings of D.C. potentials were made using the 'grease-gap' technique during continuous superfusion of the isolated nerve. Beginning at 1 nM, 5-HT induced small depolarizations that displayed a slow onset. At concentrations > or = 1 microM, large depolarizations with rapid onset were elicited. In the presence of the 5 HT3 receptor antagonists, granisetron or ondansetron, 5-HT responses were diminished and exhibited an increased latency to peak. These small, slow depolarization were not reduced by 5-HT1 or 5-HT2 receptor antagonists, but were potently inhibited by the 5-HT4 receptor antagonist GR 113808 (pA2 = 9.3), and mimicked by 5-methoxytryptamine (pEC50 = 5.3). 5-HT4-mediated responses were larger at 37 degrees C than at 31 degrees C, but also showed marked diminution with repeated 5-HT applications at concentrations greater than 1 microM. Conversely, 5-HT3 receptor responses were potentiated at lower temperatures (< or = 31 degrees C). Consistent with the reported positive coupling of 5-HT4 receptors to adenylyl cyclase, forskolin and 8-Br-cAMP produced slowly developing depolarizations which were qualitatively similar to 5-HT4 receptor activation. Pre-depolarization of nerves with 10 microM forskolin or 300 microM 8-Br-cAMP diminished the effect of 5-HT4 receptors. This study has confirmed the presence of 5-HT4 receptors on the vagus nerve of the rat and defined some conditions that optimize their pharmacological isolation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7988638 TI - 5-HT1A receptor-mediated inhibition in the hippocampus of the alert rat--effects of repeated gepirone treatment. AB - The effects of acute and repeated treatment with the 5-HT1A receptor ligand gepirone on hippocampal excitatory synaptic transmission were investigated. Recordings of the electrically evoked field population excitatory postsynaptic potentials (e.p.s.p.s) were made in the stratum radiatum of the CA1 region of the dorsal hippocampus of alert male Wistar rats. Acute injection of gepirone reduced the e.p.s.p. amplitude in a transient dose-dependent (0.5-10 mg/kg, i.p.) manner. This effect was blocked by the 5-HT1A receptor antagonist MDL 73005EF (8-[2-(2,3 dihydro-1,4-benzodioxin-2-yl methylaminoethys]-8- azaspiro[4,5]decane-7,9-dione methyl sulphonate, 2 mg/kg, i.p.). Gepirone (1 mg/kg per day, i.p.) administered for 7 days produced a gradual reduction in the daily pre-injection baseline e.p.s.p. amplitude coupled with a concomitant reduction of the acute response to the drug. The chronic baseline reduction was transiently reversed by the 5-HT1A receptor antagonist spiroxatrine and complete recovery to pretreatment levels was observed 48 h after the last gepirone dose. The data indicate that with repeated administration, a prolongation and enhancement of the 5-HT1A receptor-mediated reduction in the e.p.s.p. by gepirone occurs. This delayed effect may contribute to the slow onset of therapeutic action of gepirone. PMID- 7988639 TI - Inhibitory effect of 5 beta-pregnan-3 alpha-o1-20-one on gonadotropin-releasing hormone gene expression in the male rat. AB - Neuroanatomical data have documented the existence of synaptic contacts between gamma-aminobutyric acid (GABA) terminals and preoptic gonadotropin-releasing hormone (GnRH) neurons in the rat anterior hypothalamus. In addition, pharmacological studies have suggested that the GABAergic system may be involved in the control of gonadotropin release. Moreover, it has been shown that some progesterone metabolites such as 5 beta-pregnan-3 alpha-ol-20-one (5 beta 3 alpha P) are able to interact with the GABAA receptor complex. In the present study, we have investigated the effects of chronic (5 days) treatment with the GABAA positive ligand 5 beta 3 alpha P (20 mg/kg body weight i.p., twice a day) or with the GABAA agonist muscimol (1 mg/kg body weight i.p., twice a day) alone or in combination on GnRH mRNA levels in the preoptic area of the male anterior hypothalamus as measured by in situ hybridization. Treatment with 5 beta 3 alpha P produced a 30% decrease in the number of grains overlying labelled cells, while muscimol treatment decreased the hybridization signal by 36%. The concomitant administration of 5 beta 3 alpha P and muscimol resulted in a 46% decrease in the GnRH mRNA levels. This inhibitory effect was completely antagonized by the concomitant administration of picrotoxin (4 mg/kg body weight i.p., twice a day). These data suggest that the GABAA receptor complex and steroids that interact positively with this GABAA receptor complex may play an important role in the regulation of GnRH biosynthesis by hypothalamic neurons. PMID- 7988640 TI - Tolerance to the vascular effect of a novel nitric oxide-donating vasodilator, FK409. AB - We investigated whether tolerance develops to the vasorelaxant effects of a new vasodilator, (+-)-(E)-4-ethyl-2-[(E)-hydroxy-imino]-5-nitro-3-hexenamide (FK409), in isolated canine coronary artery strips and to its hypotensive effect in rats, and whether FK409 activates soluble guanylate cyclase isolated from vascular tissues in the absence of L-cysteine. No tolerance to FK409 (0.46 nM to 0.46 microM or 1-1000 micrograms/kg, i.v.) or cross-tolerance between FK409 and glyceryl trinitrate was demonstrated in in vitro and in vivo experiments, whereas the tolerance to glyceryl trinitrate (0.44 nM to 4.4 microM or 1-1000 micrograms/kg, i.v.) was marked in both conditions. In addition, FK409 (0.1-10 microM) activated soluble guanylate cyclase without L-cysteine, but glyceryl trinitrate (1-100 microM) required the addition of L-cysteine (5 mM) for the activation of the enzyme. The results suggest that FK409 may be advantageous compared to tolerance-producing nitrates currently in clinical use, and that this property of FK409 is probably due to its independence of a sulfhydryl group donor. PMID- 7988641 TI - Comparison of the effects of various vanadium salts on glucose homeostasis in streptozotocin-diabetic rats. AB - Oral administration of vanadium salts to severely diabetic rats lead to a spectacular decrease of plasma glucose levels in spite of the insulin deficiency of the animals. The insulin-like properties of vanadium have been attributed to the cationic form, vanadyl, into which the anionic form, vanadate, is reduced within cells. This has led to the suggestion that vanadyl is the form of choice for the treatment. In this study, rats made insulin-deficient and diabetic with streptozotocin were treated with three salts of vanadium: sodium orthovanadate, sodium metavanadate and vanadylsulfate. The salts were added to the drinking water, in concentrations that led to ingestion of the same amount of vanadium element by the three groups of rats (approximately 8 mg/kg per day). The initial, transient, loss of weight that affected the treated rats was slightly smaller in the vanadyl-treated group than in the vanadate-treated groups. However, during steady-state treatment, the three groups exhibited a similar food intake (lower than in controls) and growth rate (higher than in controls). The decreases in plasma glucose levels, in urinary volume and in glucosuria, and the improvement of the tolerance to an oral glucose load were similar regardless of the type of vanadium salt. Withdrawal of the treatment after 14 weeks was followed by a rapid increase in plasma glucose levels which, however, remained clearly lower than in controls for at least 4 weeks, whereas plasma insulin levels increased only transiently. A smaller glucosuria and a slightly better tolerance to oral glucose than in controls were still observed in the previously treated rats.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7988642 TI - Behavioral and biochemical effects of the dopamine D3 receptor-selective ligand, 7-OH-DPAT, in the normal and the reserpine-treated rat. AB - In normal rats, the dopamine D3 receptor-selective ligand, 7-hydroxy-2-(di-n propylamino)tetralin (7-OH-DPAT), produced biphasic effects on spontaneous locomotor activity, i.e. suppression at low doses (0.06-0.25 mumol kg-1 s.c.), followed by a gradual increase in motor activity (1.0-4.0 mumol kg-1). The core temperature was decreased at these latter high doses only. The reserpine-induced (8.2 mumol kg-1 s.c.) increase in neostriatal 3,4-dihydroxyphenylalanine (DOPA) accumulation, following treatment with m-hydroxybenzylhydrazine-(NSD-1015) (475 mumol kg-1 i.p.), was dose dependently antagonized by 7-OH-DPAT in the dose range 0.02-4.0 mumol kg-1. The reserpine-induced suppression of spontaneous locomotor activity, however, was antagonized at higher doses only (1.0-4.0 mumol kg-1). Finally, there were no region-selective effects of 7-OH-DPAT on DOPA accumulation in the neostriatum. Thus, it appears that the dopamine D3 receptor-preferring ligand, 7-OH-DPAT, displays the profile of a dopamine D2 receptor agonist, pre- and postsynaptically. PMID- 7988644 TI - Effect of the selective thromboxane A2 receptor antagonist, S-1452, on antigen induced sustained bronchial hyperresponsiveness. AB - Long-lasting bronchial hyperresponsiveness to i.v. acetylcholine was observed in actively sensitized guinea-pigs after aerosol ovalbumin exposure. The response became significant at 7 h post-challenge and persisted for at least 120 h compared to the response of unsensitized animals. Pretreatment of animals with the specific thromboxane A2 receptor antagonist, S-1452 (calcium (1R,2S,3S,4S) (5Z)-7-(((phenylsulfonyl)amino)bicyclo[2.2.1] hept-2-yl)hept-5-enoate dihydrate), almost completely inhibited the onset of bronchial hyperresponsiveness, as assessed at 24 and 120 h post-challenge. However, it was ineffective when administered at 1 h post-challenge or 2 h before assessment of bronchial responsiveness. Lung vascular injury occurred transiently immediately after antigen challenge, the kinetics of injury being associated with those for the production of thromboxane B2 in bronchoalveolar lavage fluid. The vascular injury was dramatically suppressed by pretreatment with S-1452. These findings suggest that acutely generated thromboxane A2 plays an important role in the pathogenesis of antigen-induced long-lasting bronchial hyperresponsiveness, probably by producing vascular damage in the lungs. PMID- 7988643 TI - Effects of tilisolol on ischemic myocardial metabolism in dogs. AB - The effects of tilisolol on ischemic myocardial energy and carbohydrate metabolism were examined, and compared with those of propranolol. Ischemia was induced by ligating the left anterior descending coronary artery for 3 or 30 min in anesthetized open-chest dogs, 5 min after saline, tilisolol (0.2 mg.kg-1, i.v.), or propranolol (1 mg.kg-1, i.v.) injection. During ischemia, the myocardial energy stores were depleted, and the levels of glycolytic intermediates were altered, associated with ST segment elevation and TQ segment depression of the epicardial electrocardiogram. Tilisolol prevented the myocardial energy depletion and alterations of carbohydrate metabolism caused by 3 min of ischemia, to the same extent as did propranolol. Even 30 min after ischemia, the prevention of these ischemic changes was sustained by tilisolol, but not by propranolol. Tilisolol briefly reduced the ST segment elevation and TQ segment depression induced by ischemia. These results suggest that the protective effects of tilisolol on the ischemic myocardium are more potent and long-lasting than those of propranolol. PMID- 7988645 TI - Characterization of the alpha 1-adrenoceptor subtype mediating contraction of guinea-pig spleen. AB - A series of alpha 1-adrenoceptor agonists evoked concentration-dependent contraction of isolated guinea-pig spleen strips ((-)-adrenaline > (-) noradrenaline >> L-phenylephrine > (-)-(4aR, 10aR)-3, 4,4a,5,10,10a-hexahydro-6 methoxy-4-methyl-9-methylthio-2H-naphth [2,3-b]-1,4-oxazine (SDZ NVI 085) > cirazoline), whereas indanidine, methoxamine, oxymetazoline and UK-14.304 were ineffective. (-)-Noradrenaline-induced contractions were inhibited by chloroethylclonidine (3 x 10(-6)-6 x 10(-5) M) and partially attenuated by SZL-49 (10(-7)-10(-6) M), but remained resistant to (+/-)-isradipine (10(-9)-10(-7) M). The contractions of the splenic strips were competitively antagonized by low concentrations of the alpha 1B-adrenoceptor-selective antagonist, spiperone (pA2 8.05), but by relatively high concentrations of the alpha 1A-adrenoceptor selective antagonists, (+)-niguldipine (pA2 6.32) and 5-methyl-urapidil (pA2 6.95). The affinities of subtype-selective antagonists determined at guinea-pig spleen alpha-adrenoceptors significantly correlated with pKi values at rat liver alpha 1B binding sites (r = 0.96) and pA2 values at putative alpha 1B adrenoceptors in rat aorta (r = 0.95), but differed from pKi values at rat cortical alpha 1A binding sites and pA2 values at alpha 1A-adrenoceptors in rat vas deferens. Also no correlation was obtained between antagonist affinities at guinea-pig spleen alpha-adrenoceptors and alpha 1C binding sites in rabbit liver. Thus, from the (1) potencies of agonists, (2) affinities of subtype-selective antagonists and (3) differential sensitivity of the contractions to alpha 1 adrenoceptor inactivating agents and their resistance to Ca2+ channel blockade, the alpha 1-adrenoceptor mediating smooth muscle contraction of guinea-pig spleen can be best characterized as being of the B subtype. PMID- 7988646 TI - Characterisation of the endothelin receptor mediating contraction of human pulmonary artery using BQ123 and Ro 46-2005. AB - We have characterised the endothelin receptor mediating contraction of human isolated pulmonary artery. Endothelin-1 induced a concentration-dependent contraction of human endothelium-denuded pulmonary artery (EC50 5.6 nM). In contrast, endothelin-3 produced only a small contraction (approximately 12% of maximum endothelin-1 response) at the highest concentration tested (1 microM). The ETB receptor-selective agonist, sarafotoxin S6c (0.1 nM to 1 microM) did not cause contraction of human pulmonary artery. Pretreatment of human pulmonary artery with BQ123 (1-10 microM), an ETA receptor-selective blocking drug, resulted in a concentration-dependent, surmountable antagonism of endothelin-1 induced contractions (apparent pKB 6.6-7.0). Schild analyses yielded a shallow slope (0.58), which was significantly less than unity and, consequently, the calculated pA2 (8.1) was greater than the individual pKB values. Pretreatment of human pulmonary artery with Ro 46-2005 (30 microM), a non-peptide. non-selective endothelin receptor-blocking drug, resulted in a surmountable antagonism of endothelin-1-induced contractions (apparent pKB 5.5). In conclusion, endothelin-1 induced contraction of human pulmonary artery appears to be mediated predominantly via ETA receptors, although the shallow Schild slope observed with BQ123 indicates possible receptor heterogeneity. PMID- 7988647 TI - The spinal analgesic role of alpha 2-adrenoceptor subtypes in rats after peripheral nerve section. AB - Two putative agonists of subtypes of alpha 2-adrenoceptors, guanfacine (alpha 2A) and ST-91 ([2,6-dicthylphenylamino]-2-imidazoline, alpha 2C), were applied intrathecally and their effects on autotomy behaviour and on the flexor reflex before and after sciatic nerve section were examined. Neither drug influenced autotomy during a 17-day observation period. Both drugs dose dependently depressed the flexor reflex in rats with intact sciatic nerves. After axotomy, the sensitivity of the flexor reflex to guanfacine and ST-91 was moderately increased compared to normals. ST-91 i.t. at high doses evoked motor discharges, an effect which was reversed by the alpha 1-adrenoceptor antagonist, WB4101 (2 [2,6-dimethyoxyphenoxyethyl]-aminomethyl-1,4-benzodioxane). Thus, the effect of i.t. clonidine on the flexor reflex and autotomy behaviour observed previously may not involve its action on alpha 2A- and alpha 2C-adrenoceptors. Furthermore, due to its motor effect which may involve activation of alpha 1-adrenoceptors, ST 91 may not be a suitable tool to study the physiological function of spinal alpha 2C-adrenoceptors. PMID- 7988648 TI - Effect of valepotriates on the behavior of rats in the elevated plus-maze during diazepam withdrawal. AB - The effect of a mixture of valepotriates on the elevated plus-maze performance of diazepam withdrawn rats was evaluated. The rats were chronically (28 days) treated with diazepam (doses increased up to 5.0 mg/kg) and then treated with control solution for 3 days to induce a withdrawal syndrome. Chronically vehicle treated rats were used as control. The abstinent animals treated with vehicle showed a significant decrease in the percentage of time spent in the open arms when compared with the control animals. Diazepam and valerian 12.0 mg/kg reversed this anxiogenic effect. Valerian 6.0 mg/kg did not show any difference in relation to the others group. PMID- 7988650 TI - Chronic treatment with citalopram facilitates the effect of a challenge dose on cortical serotonin output: role of presynaptic 5-HT1A receptors. AB - In animals given citalopram (10 mg/kg) twice daily for 14 days a further dose of 1 mg/kg, administered 24 h after the last dose, markedly increased cortical dialysate serotonin (5-hydroxytryptamine, 5-HT), but had no effect in control animals. The effect on dialysate 5-HT in the dorsal raphe was not increased by the chronic treatment. At 25 micrograms/kg, 8-hydroxy-2-(di-n propylamino)tetralin, an agonist at 5-HT1A receptors, reduced cortical 5-HT output in controls but not in animals treated chronically with citalopram whereas 50 micrograms/kg reduced 5-HT output in both groups. These findings suggest that somatodendritic 5-HT1A receptors are desensitized after chronic treatment with citalopram and this results in facilitation of its effect on cortical dialysate 5 HT. These results also agree with the concept that the effect of 5-HT re-uptake inhibitors on increasing 5-HT output in the frontal cortex is attenuated by their simultaneous ability to activate somatodendritic 5-HT1A receptors via an increase of endogenous 5-HT in the raphe region. PMID- 7988649 TI - Catalepsy-associated behavior induced by dopamine D1 receptor antagonists and partial dopamine D1 receptor agonists in squirrel monkeys. AB - Observational procedures were used to compare the behavioral effects of dopamine D1 receptor antagonists and partial dopamine D1 receptor agonists in squirrel monkeys. The dopamine D1 receptor antagonists SCH 39166 ((-)-trans-6-7,7a,8,9,13b hexahydro-3-chloro-2-hydroxy-N- methyl-5H-benzo(d)naphtho-(2,1-b)azepine) and BW 737C89 ([S]-6-chloro-1-[2,5-dimethoxy-4-propylbenzyl]-7- hydroxy-2-methyl-1,2,3,4 tetrahydroisoquinoline) produced dose-related increases in the duration of static and unusual postures, indicative of catalepsy. R-SKF 38393 (R(+)-7,8- dihydroxy-1 phenyl-2,3,4,5-tetrahydro-[1H]-3-benzazepine) and SKF 75670 (7,8-dihydroxy-3 methyl-1-phenyl-2,3,4,5-tetrahydro-[1H]-3- benzazepine), which are considered partial dopamine D1 receptor agonists, also consistently produced dose-related increases in catalepsy-associated behavior and had effects comparable in magnitude to those of dopamine D1 receptor antagonists. In contrast, the higher efficacy D1 agonists SKF 81297 (6-chloro-7,8-dihydroxy-1-phenyl-2,3,4,5 tetrahydro-[1H]-3- benzazepine) and SKF 82958 (6-chloro-7,8-dihydroxy-1-phenyl 2,3,4,5-tetrahydro-3-allyl-[1H]-3- benzazepine) did not produce catalepsy associated behavior at any dose tested. The results indicate that dopamine D1 agonists differ with respect to cataleptogenic activity, possibly reflecting differences in intrinsic activity. PMID- 7988651 TI - The effect of different corticosteroids and cyclosporin A on interleukin-4 and interleukin-5 release from murine TH2-type T cells. AB - By secretion of interleukin-4 and interleukin-5, TH2-type T cells are thought to play an important role in the pathogenesis of asthma. Corticosteroids are currently the most effective therapy available for asthma, but recently it has been demonstrated that cyclosporin A improves lung function in patients with severe corticosteroid-dependent asthma. In order to examine the effects of corticosteroids and cyclosporin A on anti-CD3-induced production of interleukin-4 and interleukin-5 we used the murine TH2-type cell clone D10.G4.1. Interleukin 4/interleukin-5 release was inhibited by all drugs tested with the following IC50 values (nmol/l) for interleukin-4 and interleukin-5, respectively: budesonide (0.32/0.22), beclomethasone (0.65/0.33), dexamethasone (4.70/3.52), 6 alpha methyl-prednisolone (24.04/17.02), hydrocortisone (34.27/22.55), and cyclosporin A (72.59/242.21). In conclusion, corticosteroids exert strong inhibitory effects on cytokine production by TH2-cells, which may explain, at least partly, its clinical efficacy in asthma. Cyclosporin A also showed a concentration-dependent inhibition; however, in relation to corticosteroids the inhibitory activity of cyclosporin A was found to be weaker. PMID- 7988653 TI - Antitussive effect of dihydroetorphine in mice. AB - The present study examined the opioid receptors involved in the antitussive effect of dihydroetorphine in mice. Dihydroetorphine suppressed coughs dose dependently at doses between 0.1-1 micrograms/kg i.p. Blockade of mu-opioid receptors by pretreatment with beta-funaltrexamine significantly reduced the antitussive effect of dihydroetorphine. Furthermore, the antitussive effect of dihydroetorphine was also antagonized by nor-binaltorphimine, a kappa-opioid receptor antagonist. However, pretreatment with naltrindole, a delta-opioid receptor antagonist, did not affect the antitussive effect of dihydroetorphine. These results indicate that the antitussive effect of dihydroetorphine is mediated by the activation of mu-opioid receptors and of kappa-opioid receptors, but not delta-opioid receptors. PMID- 7988652 TI - Further evidence for the importance of 5-HT1A autoreceptors in the action of selective serotonin reuptake inhibitors. AB - The clinical efficacy of antidepressants that block serotonin (5 hydroxytryptamine, 5-HT) reuptake may be restrained by indirect activation of autoreceptors. In vivo microdialysis in rat hippocampus was used to assess the release-inhibitory properties of the 5-HT reuptake inhibitors citalopram and paroxetine. When reuptake was first blocked by infusing citalopram into the hippocampus, systemic administration of citalopram or paroxetine resulted in a 50 70% decrease in hippocampal 5-HT overflow. This presumably reflected the inhibition of 5-HT release subsequent to reuptake blockade in the raphe nuclei and, in turn, activation of somatodendritic autoreceptors. In support, pretreatment with (+/-)-pindolol or (+)-WAY100135 ((+)-N-tert-butyl-3-(4-(2- methoxyphenyl)piperazine-1-yl)-2-phenylpropanamide dihydrochloride), to block 5 HT1A autoreceptors, abolished the decrease in 5-HT produced by systemic injection of the uptake blockers. PMID- 7988654 TI - EXP597, a nonpeptide angiotensin II receptor antagonist with high affinities for the angiotensin AT1 and AT2 receptor subtypes. AB - AT1 and AT2 are the two major receptor subtypes for angiotensin II that have been pharmacologically defined by using the selective ligands losartan and PD123177, respectively. EXP597 (4-[(5-(2-benzoyl)benzyloxycarbonyl-4-ethyl-2-n propylimidazole-1- yl)methyl]-3-fluoro-2'-isoamyloxycarbonylaminosulfonyl-[1,1'] biph enyl, potassium salt) is a nonpeptide angiotensin II receptor ligand which in the rat adrenal exhibits binding affinities (IC50) of 0.5 and 0.7 nM for angiotensin AT1 and AT2 receptor subtypes, respectively. Further, EXP597 is an insurmountable angiotensin II receptor antagonist in the isolated rabbit aorta and lowers blood pressure in renal hypertensive rats with i.v. and p.o. ED30 values of 0.05 and 0.9 mg/kg, respectively. PMID- 7988655 TI - Constitutive nitric oxide modulates the injurious actions of vasopressin on rat intestinal microcirculation in acute endotoxaemia. AB - The administration of the nitric oxide (NO) synthase inhibitor, NG-nitro-L arginine methyl ester (L-NAME, 5 mg/kg s.c.) concurrently with Escherichia coli endotoxin (3 mg/kg i.v.) increased vascular permeability and caused mucosal damage in the rat intestine 1 h later. The vasopressin V1 receptor antagonist, [Mca1,Tyr(Me)2, Arg8]vasopressin (0.01-0.2 microgram/kg s.c., 15 min before endotoxin) dose-dependently reduced this damage. These results suggest a beneficial role of NO, counteracting the injurious vascular actions of endogenous vasopressin, in maintaining intestinal mucosal integrity in acute endotoxaemic states. PMID- 7988656 TI - Effects of CD-832, a dihydropyridine derivative with a nitrate ester moiety on rabbit femoral artery and vein. AB - We investigated the effects of CD-832 ((4R)-(-)-2-(nicotinoyl-amino)ethyl 3 nitroxypropyl 1,4-dihydro-2,6-dimethyl-4,3-nitrophenyl, 3,5-pyridine dicarboxylate), a dihydropyridine derivative with a nitrate ester moiety, on contractile responses in rabbit femoral arteries and veins. CD-832 (10(-8) to 10( 6) M and nifedipine inhibited the 64 mM KCl-induced and 10(-6) M norepinephrine induced contractions of rabbit femoral arteries, while nitro compounds had no effect on the contractions. CD-832 (10(-8) to 10(-6) M) and nitro compounds inhibited the 10(-6) M norepinephrine-induced contractions in rabbit femoral veins, while other Ca2+ channel antagonists had little effect. The inhibitory effects of CD-832 (10(-7) M) on norepinephrine-induced contractions were antagonized by treatment with methylene blue (10(-5) M). These results indicate that CD-832 potently relaxes venous smooth muscle, and that it may be a useful agent for the treatment of angina pectoris. PMID- 7988657 TI - Inhibition of respiratory burst in macrophages by complement receptor blockade. AB - Respiratory burst activity was induced in rat peritoneal macrophages by opsonized zymosan. Inhibitors were tested by administering them before or after the inducing agent: OX-42, an anti-rat macrophage complement receptor type 3 antibody, was active at an estimated concentration of 2.1 nM, and was more than 100-fold more potent when administered before, rather than after, opsonized zymosan. Indomethacin and dapsone, two agents with antiinflammatory activity, were also more effective before opsonized zymosan, but only in the 10(-3) to 10( 4) molar range. Inhibitors of eicosanoid synthesis, as well as the antiinflammatory prostaglandin E2, also reduced the respiratory burst. PMID- 7988658 TI - Hsp70 in mitochondrial biogenesis: from chaperoning nascent polypeptide chains to facilitation of protein degradation. AB - The family of hsp70 (70 kilodalton heat shock protein) molecular chaperones plays an essential and diverse role in cellular physiology. Hsp70 proteins appear to elicit their effects by interacting with polypeptides that present domains which exhibit non-native conformations at distinct stages during their life in the cell. In this paper we review work pertaining to the functions of hsp70 proteins in chaperoning mitochondrial protein biogenesis. Hsp70 proteins function in protein synthesis, proteins to proteolytic enzymes in the mitochondrial matrix. PMID- 7988660 TI - Hsp70s and lysosomal proteolysis. AB - Confluent cultured cells activate a lysosomal pathway of polypeptide breakdown in response to withdrawal of serum growth factors. The substrates for this proteolytic pathway are a restricted class of cytosolic polypeptides containing peptide sequences biochemically related to lysine-phenylalanine-glutamate arginine-glutamine, or, in single amino acid abbreviations, KFERQ. The heat shock cognate protein of 73 kD (hsc73) binds to a variety of polypeptides via this molecular determinant and facilitates their lysosomal import and degradation. In addition, a portion of intracellular hsc73 resides within the lysosome and appears to be an essential component of the proteolytic machinery. Several potential mechanisms by which hsc73 mediates selective lysosomal import and degradation of polypeptides are discussed. PMID- 7988661 TI - Molecular chaperones in the processing and presentation of antigen to helper T cells. AB - Helper T lymphocytes recognize peptide fragments of antigen bound to Major Histocompatibility Complex (MHC) class II molecules on the surfaces of antigen presenting cells (APC). Antigen processing involves internalization of the antigen into an acidic compartment where the antigen is degraded and the resulting peptide fragments of the antigen are bound to MHC class II molecules and the complexes subsequently displayed at the APC surface. Thus, antigen processing represents a complex, intracellular assembly process which may, like many intracellular protein folding and assembly processes, require the function of molecular chaperones. This contribution focuses on the evidence which suggests that members of the heat shock protein family of molecular chaperones play a role in this pathway. PMID- 7988659 TI - BiP (GRP78), an essential hsp70 resident protein in the endoplasmic reticulum. AB - BiP is a constitutively-expressed resident protein of the endoplasmic reticulum (ER) of all eucaryotic cells, and belongs to the highly conserved hsp70 protein family. In the ER, BiP is involved in polypeptide translocation, protein folding and presumably protein degradation as well. These functions are essential to cell viability, as has been shown for yeast. In this review, I will summarize the structural features of hsp70 proteins and focus on those experiments which revealed the biological function of BiP. PMID- 7988662 TI - Protective effects of hsp70 in inflammation. AB - Inflammation results from the recruitment to a given tissue or organ and the activation of leucocytes, among which the monocytes-macrophages play a major role. These phagocytic cells produce high levels of reactive oxygen species (ROS) as well as cytokines. Whereas both ROS and cytokines have the potential to regulate the expression of heat shock (HS)/stress proteins (HSP), it appears that these proteins in turn have the ability to protect cells and tissues from the deleterious effects of inflammation. The mechanisms by which such protection occurs include prevention of ROS-induced DNA strand breaks and lipid peroxidation as well as protection from mitochondrial structure and function. In vivo, HS protects organs against a number of lesions associated with the increased production of ROS and/or cytokines. In an animal model for adult respiratory distress syndrome, an acute pulmonary inflammatory condition, HS completely prevented mortality. HSP (hsp70 in particular) may also exert protective effects in the immune system by contributing to the processing and presentation of bacterial and tumoral antigens. The analysis of the expression of hsp70 may prove of diagnostic and prognostic value in inflammatory conditions and therapeutical applications are being considered. PMID- 7988663 TI - Heat shock proteins and virus replication: hsp70s as mediators of the antiviral effects of prostaglandins. AB - Acute infection of mammalian cells with several types of RNA and DNA viruses often results in induction of heat-shock gene expression. The presence of hsp70 in intact virions, as well as the transient association of HSP with viral proteins and assembly intermediates during virus replication, has also been reported in several experimental models. Moreover, a possible role of heat shock proteins in the beneficial effect of fever and local hyperthermia during acute virus infection has been hypothesized. However, the role of HSP in virus replication remains to be defined. At the beginning of the 1980s, the use of virus models to investigate the molecular events that follow the exposure of mammalian cells to prostaglandins led to the serendipitous discovery that specific arachidonic acid derivatives are potent inhibitors of virus replication. This finding was rapidly followed by the observation that treatment of virus infected cells with the antiviral prostaglandin A1 (PGA1) resulted in the accumulation of a 70 KDa cellular protein, which was identified as hsp70. It is now well established that cyclopentenone prostaglandins, which exert potent antiviral activity in several DNA and RNA virus models, induce hsp70 synthesis through cycloheximide-sensitive activation of heat shock transcription factor. This chapter discusses the role of heat shock proteins in the control of virus replication and summarizes the results of our recent work, which indicate that hsp70 is actively involved in the antiviral activity of prostaglandins. PMID- 7988664 TI - Role of hsp70 in cytokine production. AB - Interleukin-1 and tumor necrosis factor-alpha are potent, multifunctional cytokine mediators of inflammation and immune responses that are produced primarily by activated monocytes and macrophages. Three published papers by different groups have shown that heat shock and chemical stress with heavy metal salts or sulfhydryl reagents, all of which induce the expression of heat shock protein 70 (hsp70), concomitantly inhibit the production of these cytokines in human monocytes and mouse macrophages activated by lipopolysaccharide. These papers are reviewed and discussed in some detail. Other studies suggest that various anti-inflammatory drugs, including acetylsalicyclic acid, auranofin and dexamethasone, can also facilitate HSP expression in macrophages. However, while these studies are interesting, it is clear that not a great deal of work has been done and/or published in this area. Since many pharmaceutical companies are developing cytokine synthesis inhibitors as potential anti-inflammatory drugs, one aim of this article is to emphasize that understanding the molecular mechanism(s) that lead to increased HSP expression and decreased cytokine biosynthesis may assist in achieving this goal. PMID- 7988665 TI - Heat shock proteins in immune response to cancer: the Fourth Paradigm. AB - The involvement of heat shock proteins in immune response is categorized into four distinct paradigms. In the First Paradigm, HSP derived from foreign organisms act as classical foreign antigens, and they elicit immune response to the non-conserved HSP epitopes. The Second Paradigm refers to instances where the host responds to self HSP to which there is no central or peripheral tolerance. The Third Paradigm involves molecular mimicry, where cross-reactivity between an HSP and another protein leads to an immune response to the latter under conditions which elicit an immune response to the former, such as infection with a bacterium whose immunodominant antigen is an HSP. The Fourth Paradigm refers to situations where an HSP-antigen complex elicits an effective response to the antigen and not to the HSP. Thus the HSP acts as a carrier for the antigenic peptide. The role of HSP in recognition by gamma delta T cells may also fall into this paradigm. In this article, the Fourth Paradigm is considered as a crucial element in the development of vaccines against cancers and infectious diseases, and is analyzed through the prism of the observed association of hsp70 species with antigenic peptides. PMID- 7988667 TI - Hsp70 in myocardial ischaemia. AB - Numerous reports suggest that stress protein accumulation confers protection in various mammalian tissues against differing stresses. The purpose of this article is to review the evidence that stress proteins, in particular hsp70, are able to alter the resistance of the heart to subsequent ischaemic and non-ischaemic injury and to discuss the possible physiological basis for this apparent protection. The possible, though unlikely involvement of heat stress proteins in classical ischaemic preconditioning is addressed as is the possibility of their involvement in a delayed second window of protection. PMID- 7988666 TI - Hsp70 in parasites: as an inducible protective protein and as an antigen. AB - The heat shock (HS) response is a general homeostatic mechanism that protects cells and the entire organism from the deleterious effects of environmental stresses. It has been demonstrated that heat shock proteins (HSP) play major roles in many cellular processes, and have a unique role in several areas of cell biology, from chronic degenerative diseases to immunology, from cancer research to interaction between host and parasites. This review deals with the hsp70 gene family and with its protein product, hsp70, as an antigen when pathogens infect humans. Members of HSP have been shown to be major antigens of many pathogenic organisms when they experience a major temperature shift upwards at the onset of infection and become targets for host B and T cells. PMID- 7988669 TI - Hsp70 and aging. AB - An alteration in the ability of cells to express heat shock proteins could be physiologically important in aging because all living organisms show a reduced ability to respond to stress with increasing age. Using hepatocytes freshly isolated from young adult and old rats, we have shown that the induction of hsp70 expression by heat shock is reduced approximately 50% with age. The decrease in hsp70 expression occurs at the level of transcription and appears to arise from a defect in the heat shock transcription factor. Other investigators have also shown that the induction of hsp70 expression by heat shock as well as other stresses declines significantly with age in a variety of tissues from rats as well as mononuclear cells from human subjects. In addition, a decrease in the inducibility of hsp70 is observed with cell senescence in cultured cells. Therefore, it appears that a reduced ability to express hsp70 in response to stress may be a common phenomenon underlying the aging process. PMID- 7988668 TI - Heat shock response in the central nervous system. AB - The heat shock response is induced in nervous tissue in a variety of clinically significant experimental models including ischemic brain injury (stroke), trauma, thermal stress and status epilepticus. Excessive excitatory neurotransmission or the inability to metabolically support normal levels of excitatory neurotransmission may contribute to neuronal death in the nervous system in many of the same pathophysiologic circumstances. We demonstrated that in vitro glutamate-neurotransmitter induced excitotoxicity is attenuated by the prior induction of the heat shock response. A short thermal stress induced a pattern of protein synthesis characteristic of the highly conserved heat shock response and increased the expression of heat shock protein (HSP) mRNA. Protein synthesis was necessary for the neuroprotective effect. The study of the mechanisms of heat shock mediated protection may lead to important clues as to the basic mechanisms underlying the molecular actions of the HSP and the factors important for excitotoxic neuronal injury. The clinical relevance of these findings in vitro is suggested by experiments performed by others in vivo demonstrating that pretreatment of animals with a submaximal thermal or ischemic stress confers protection from a subsequent ischemic insult. PMID- 7988671 TI - Comparative study of the karyotypes of two Egyptian species of bats, Taphozous perforatus and Taphozous nudiventris (Chiroptera: Mammalia). AB - A detailed karyotypic analysis of two Egyptian species of bats, Taphozous perforatus and Taphozous nudiventris, was made on the basis of conventional data and G-band patterns. No detectable karyotypic difference was found between the two species (2n = 42, F. N. 64). By comparison of G-band patterns, some differences between the two species were seen in the corresponding autosomal pairs. These results are reported for the first time in Egypt. PMID- 7988672 TI - A new flavone glycoside from the fern Pteris cretica. AB - A new flavone glycoside isolated from the fern Pteris cretica has been shown to be luteolin 7-O-robinobioside (1) by chemical and spectral methods. In addition luteolin 7-O-rutinoside (2) and luteolin 7-O-glucoside (3) have been isolated from this plant. Flavonoid 2 is reported for the first time in ferns. PMID- 7988670 TI - Heritable trinucleotide repeats and neurological disorders. AB - In the past 3 years, seven human neurological disorders have been found to be associated with an abnormal number of unstable trinucleotide repeats within exons or non-expressed regions of a gene. These forms of mutations are called dynamic mutations. The expansion in copy number of trinucleotide repeats may represent a large number of hereditary disorders. The correlation between the length of the repeated size and the disease severity and variable onset has provided some genetic explanation for a phenomenon called anticipation. However, there are numerous questions which cannot be explained by anticipation. Many other factors such as genomic imprinting and variable DNA methylation may also contribute to the puzzling features of these phenotypes. PMID- 7988675 TI - Common structural motifs in small proteins and domains. PMID- 7988674 TI - Genetic aspects of the hsp70 multigene family in vertebrates. AB - The family of genes encoding heat shock proteins of about 70 kDa (hsp70) in vertebrates is reviewed under genetic aspects. After a detailed description of the various hsp70 genes more general characteristics of the organization and evolution of the multigene family are discussed. PMID- 7988676 TI - In vivo and in vitro effects of mutagenesis of active site tyrosine residues of mercuric reductase. AB - X-ray crystal structure analysis of mercuric reductase suggested that the binding site for Hg2+ consisted of two tyrosine residues, Tyr264 and Tyr605, as well as two cysteine residues, Cys207 and Cys628. We have previously shown that mutagenesis of Tyr605 to Phe lowered the kcat of the enzyme 6-fold, whereas the same mutation of Tyr264 resulted in a reduction of 160-fold [(1993) Biochemistry 32, 7475-7478]. Tyr605 occupies the same position in mercuric reductase as the active site His residue in the related enzyme glutathione reductase. The mutation of Tyr605 of mercuric reductase to a His residue produced a 24-fold decrease in kcat and a 15-fold decrease in Km. The in vivo resistance to Hg2+ of E. coli strains carrying wild type or mutant merA genes correlated with the in vitro measurements of kcat/Km for mercuric reductase activity. PMID- 7988673 TI - Hsp70--a multi-gene, multi-structure, multi-function family with potential clinical applications. PMID- 7988677 TI - Developmental regulation of gene expression for the MPTP delta isoforms in the central nervous system and the immune system. AB - MPTP delta is a murine transmembrane protein tyrosine phosphatase which has three isoforms, types A-C, differing in the structure of the extracellular regions. In this study, we examined MPTP delta isoform expression in the brain and the immune system at discrete developmental or differentiation stages. RT-PCR analysis demonstrated that another isoform, type D, is transcribed from the MPTP delta gene. In the brain, only type D was expressed until postnatal day 7 (P7), but after P14, all four isoforms were detected. In contrast, the spleen, thymus and all the hematopoietic cell lines examined express only types B and C isoforms. An in situ hybridization study showed that MPTP delta mRNA is diffusely expressed throughout the spleen, but its expression in the thymus is restricted to the medullary region. PMID- 7988678 TI - APS-sulfotransferase activity is identical to higher plant APS-kinase (EC 2.7.1.25). AB - A cDNA from Arabidopsis thaliana L. Heynh encoding the APS-kinase (EC 2.7.1.25) was modified by deletion of a plastidic transit peptide to enable its expression in Escherichia coli. The resultant protein (MW 25,761) is enzymatically active as APS-kinase and restores prototrophic growth in an APS-kinase mutant. All transformants harbouring the modified plant DNA also acquired APS sulfotransferase activity. In the absence of ATP but provided with DTT, a tetrameric form of recombinant APS-kinase exhibits APS-sulfotransferase activity. Monospecific polyclonal antibodies raised against the APS-kinase as immunogen also reacted against APS-sulfotransferase. We propose that APS-sulfotransferase activity is a nonphysiological side reaction of APS-kinase. PMID- 7988679 TI - Pyridine dinucleotide biosynthesis in archaebacteria: presence of NMN adenylyltransferase in Sulfolobus solfataricus. AB - The enzyme NMN adenylyltransferase, leading to NAD synthesis, has been observed for the first time in soluble extracts from the extreme acidothermophilic archaeon Sulfolobus solfataricus. Comparison of its molecular and kinetic properties with those of the enzyme isolated from prokaryotes and eukaryotes revealed significant differences, knowledge of which may contribute to the understanding of metabolic evolutionary mechanisms. The thermophilic enzyme shows a molecular mass of about 66,000 and an isoelectric point of 5.4. The Km values for ATP, NMN and nicotinic acid mononucleotide are 0.08 microM, 1.4 microM and 17 microM, respectively. The enzyme shows a remarkable degree of thermophilicity, with an activation energy of 95 kJ/mol. PMID- 7988680 TI - Substrate recognition by casein kinase-II: the role of histidine-160. AB - Casein kinase-II (CK-II) belongs to the protein kinases recognizing serine/threonine in proximity to acidic residues in protein substrates. Crystallography and mutagenesis studies on the cAMP-dependent protein kinase (PKA) disclosed that glutamic acid-170 (E170), is important for interaction of substrates with the enzyme. At a position corresponding to E170 in PKA most Ser/Thr kinases have an aspartic or glutamic acid, while CK-II has a histidine residue (H160). In order to examine the relevance of this substitution for CK-II substrate specificity, a mutant of the catalytic alpha subunit (H160D), in which H160 was changed to aspartic acid, was made. Our results show that H160 is not primarily involved in canonical substrate recognition, but does interact with an acidic residue located at position -2 with respect to the target Ser/Thr. PMID- 7988681 TI - Cloning and characterisation of the human 5-HT5A serotonin receptor. AB - The human 5-HT5A serotonin receptor has been cloned. As with the mouse and rat 5 HT5A receptors, the gene consists of two coding exons separated by a large intron. The deduced amino acid sequence of the gene reveals a protein of 357 residues which shares 93% (nucleotide) and 84% (amino acid) identity to the cloned mouse 5-HT5A receptor. We have determined the tissue distribution of the receptor by reverse transcriptase-PCR and found expression in all regions of the brain examined with little or no expression in peripheral tissues. The receptor has been transiently expressed in Cos M6 cells and exhibits a pharmacological profile closely resembling the mouse and rat 5-HT5A receptors with high, specific binding for ergotamine and methiothepin. PMID- 7988682 TI - Expression of cytochrome P-450 3A in HT29-MTX cells and Caco-2 clone TC7. AB - HT-29 sublines and Caco-2 clones were analyzed for the expression of cytochrome P 450 3A. The enzyme was found to be expressed in differentiated HT-29 cells selected by resistance to methotrexate and in one of seven Caco-2 clones, TC7. Its expression parallels the differentiation process, with highest levels being observed at late confluency. P-450 3A mRNA and protein patterns, as well as subcellular distribution, are intermediate between those observed in human adult intestine and fetal liver. PMID- 7988684 TI - Intramolecular interactions in vinculin control alpha-actinin binding to the vinculin head. AB - Using blot overlay techniques we have investigated the interaction of vinculin with alpha-actinin. We show that an alpha-actinin binding site is located in the 90 kDa vinculin head and confirm a vinculin binding site in the C-terminal rod of alpha-actinin, as recently reported by McGregor et al. [(1994) Biochem. J. 310, 225-233]. The isolated vinculin head binds much more strongly to alpha-actinin than intact vinculin. Using a proteolytic 81 kDa head fragment, we show that vinculin residues 1-107 are required for alpha-actinin binding. Antibodies directed against vinculin residues 808-850 inhibit the vinculin-alpha-actinin binding, suggesting that this sequence is directly involved in, or topographically related to, the alpha-actinin binding site. PMID- 7988683 TI - Cysteines of chloroplast NADP-malate dehydrogenase form mixed disulfides. AB - Chloroplast NADP-malate dehydrogenase (NADP-MDH) from pea and from spinach was N terminally truncated by limited proteolysis with Staphylococcus aureus protease V8. The resulting monomeric enzymes lacking, respectively, the 37 and 38 N terminal amino acids were inactive. Reduction and addition of low concentrations of guanidine-HCl (50-100 mM) resulted in a highly active enzyme of 850 units per mg protein. Equilibration of the truncated enzyme with various glutathione (GSH) redox buffers and assaying its activity in the presence of guanidine-HCl was used to establish the existence of protein-GSH mixed disulfides. This finding was further confirmed using incorporation of radioactively labelled thiol. The possible function of such cysteine modifications under oxidative stress and their regeneration by the thioredoxin system in the light is discussed. PMID- 7988685 TI - Conformation of the C-terminus of endothelin-1 in aqueous solution studied by Monte-Carlo simulation. AB - The conformation of the C-terminus of endothelin-1 in an aqueous solution has been analyzed by a Monte-Carlo simulation including the hydration energy term. The C-terminus may adopt multiple or flexible conformations in the solution, but the classification of the conformations shows that a comparably large number of conformers take a similar folding form in which the C-terminal chain is extended along the alpha-helix of the N-terminal core, and hydrophobic clusters are formed between the side groups of the C- and N-terminus. The aromatic ring of Trp21 is located at a certain distance from the two charged side groups of Asp8 and Glu10, and the functional groups of the key residues in the N-terminus are uncovered with the C-terminus tail. PMID- 7988686 TI - A possible role of sphingosine in induction of apoptosis by tumor necrosis factor alpha in human neutrophils. AB - Treatment of human neutrophils with tumor necrosis factor-alpha (TNF-alpha) resulted in an increase in concentration of ceramide and its catabolite, sphingosine. Sphingosine, a potent endogenous protein kinase C (PKC) inhibitor, as well as TNF-alpha, induced internucleosomal DNA fragmentation and morphological changes characteristic of apoptotic cells. Ceramide and sphingosine 1-phosphate, the initial product of sphingosine catabolism, did not cause apoptosis under our experimental conditions. In addition, 1-(5 isoquinolinesulfonyl)-2-methylpiperazine (H7) and N,N-dimethylsphingosine (DMS), known as PKC inhibitors, also induced apoptosis, suggesting that induction of apoptosis by sphingosine may be related to inhibition of PKC activity. These results indicate that sphingosine deacylated from ceramide may be an endogenous modulator mediating apoptotic signals by TNF-alpha in neutrophils. PMID- 7988687 TI - Alteration of the substrate specificity of human lysozyme by site-specific intermolecular cross-linking. AB - Human lysozyme dimers were prepared by the intermolecular cross-linking of the monomer that contained the mutation of either Arg41 to Cys or Ala73 to Cys with a divalent maleimide compound. Among the three kinds of possible dimers only R41C R41C dimer, in which the two catalytic clefts can come close to each other due to the proximity of the conjugation site to the active sites, turned out to be 2.3 times more specific to a polymer substrate, ethylene glycol chitin, as compared to an oligomer substrate, PNP-(GlcNAc)5. The result indicates that it is possible to alter the substrate specificity of an enzyme by artificially controlling the orientation of the active sites. PMID- 7988688 TI - Inhibition of growth and cysteine proteinase activity of Staphylococcus aureus V8 by phosphorylated cystatin alpha in skin cornified envelope. AB - The activity of a cysteine proteinase purified from Staphylococcus aureus V8 (SAV8) was inhibited by phosphorylated cystatin alpha (P-cystatin alpha) and by purified cornified envelope protein of newborn rat, a conjugated form of P cystatin alpha. Immunohistochemical analysis demonstrated a marked decrease in P cystatin alpha content in cornified envelope treated with sphingosine. The inhibition of papain activity by proteins from sphingosine-treated skin was much weaker than that exerted by proteins from the untreated skin. The suppression of SAV8 colony formation inoculated on the sphingosine-treated skin was examined. Colony formation on the sphingosine-treated skin was enhanced compared to that on normal skin. These findings suggest that P-cystatin alpha in the cornified envelope may have a bacteriostatic barrier function against bacterial infection, such as that with SAV8. PMID- 7988689 TI - Low-temperature magnetic circular dichroism investigation of the active site of chloroperoxidase. AB - Magnetic circular dichroism (MCD) spectra for near UV and visible spectral regions of chemically reduced chloroperoxidase from Caldariomyces fumago have been recorded at temperatures from near 293 to 2.15 K. The spectra of reduced chloroperoxidase at 4.2 K were compared with those of photolysis products of its carbon monoxide complexes. Obtained results give evidence for high rigidity of the active site in chloroperoxidase and strongly suggest that thiolate is a protein-derived ligand of the heme iron in the reduced enzyme. The unusual high spin ferrohemoproteins temperature dependence of the Soret MCD closely resembles that of the substrate-bound cytochrome P-450cam. PMID- 7988690 TI - The hsc70 gene which is slightly induced by heat is the main virus inducible member of the hsp70 gene family. AB - We have found that SV40 infection of CV1 cells induces the synthesis of a 72 kDa protein that upon molecular cloning was shown to be the product of the hsc70 gene. The above gene product was found to be mainly virus inducible, in contrast to the hsp70 gene product which was mainly heat inducible. The two genes were found to be cell cycle regulated in a distinctively different manner. PMID- 7988691 TI - Singlet molecular oxygen production in the reaction of peroxynitrite with hydrogen peroxide. AB - Peroxynitrite and hydrogen peroxide are mediators of cytotoxicity. This study shows that the peroxynitrite anion reacts with hydrogen peroxide to release oxygen accompanied by emission of chemiluminescence (CL). Direct characterization of this light emission attributes it to the transition of singlet molecular oxygen to the triplet ground state. Chemiluminescence was monitored: (i) by dimol light emission in the red spectral region (> 610 nm) using a red-sensitive photomultiplier; and (ii) by monomol light emission in the infrared (1270 nm) with a liquid nitrogen-cooled germanium diode. These properties of photoemission and the enhancing effect of deuterium oxide on CL intensity as well as the quenching effect of sodium azide are diagnostic of molecular oxygen in the excited singlet state. For comparison, singlet molecular oxygen arising from the thermolysis of the water-soluble endoperoxide of 3,3'-(1,4 naphthylidene)dipropionate or from the hypochlorite/H2O2 system was also monitored. These novel observations identify a potential singlet oxygen-dependent mechanism contributing to cytotoxicity mediated by peroxynitrite and hydrogen peroxide. PMID- 7988692 TI - Structure of leech derived tryptase inhibitor (LDTI-C) in solution. AB - The three-dimensional solution structure of the leech derived tryptase inhibitor form C (LDTI-C), an inhibitor of 46 amino acids which contains 3 disulfide bridges, has been determined using 2D NMR spectroscopy. The 3D structure was determined on the basis of 262 interresidue interproton distance constraints derived from nuclear Overhauser enhancement measurements and 25 phi angles, supplemented by 3 psi and 15 chi 1 angles. The core of LDTI-C is very well defined and consists of a short 3(10)-helix-loop and a short two-stranded antiparallel beta-sheet between residues 13-14 and 20-21. The N-terminus is fixed to the core by two disulfide bridges, while the C-terminus is connected to the beta-sheet via the third disulfide bridge. The binding loop in LDTI exhibits lowest energy conformations belonging to the canonical conformation of serine proteinase inhibitors. PMID- 7988693 TI - Irreversible light-induced formation of P680+ and reduced cytochrome b559 in the D1-D2-Cyt b-559 complex at low temperature. AB - Cytochrome b559 in D1-D2-Cyt b-559 complexes from spinach can be photoreduced in the presence of DBMIB at a temperature of 180-240 K upon continuous illumination. The reduction of Cyt b-559 is accompanied by oxidation of P680. At 240 K recombination of P680+ and reduced Cyt b-559 is complete in several seconds. At 220 K and below, the state P680+Cyt b-559red can be trapped for a long time. This indicates that the photoreduced heme is incapable of electron transfer to P680+ at 220 K and below. On the other hand, the chemically reduced heme of Cyt b-559 is oxidized by P680+ at 77 K. These results are consistent with the presence of two kinds of Cyt b-559 hemes in D1-D2-Cyt b-559 complexes which participate in different ways in the photochemical reactions. PMID- 7988694 TI - 6-ketocholestanol abolishes the effect of the most potent uncouplers of oxidative phosphorylation in mitochondria. AB - The effect of a keto-derivative of cholesterol, namely, 6-ketocholestanol (5 alpha-cholestan-3 beta-ol-6-one; kCh) on the uncoupling of oxidation and phosphorylation by various uncouplers was studied in rat heart mitochondria. kCh was found to completely abolish the uncoupling effect (the increase in the respiration rate under the respiratory control conditions and the decrease in the membrane potential) caused of FCCP, CCCP and SF6847 and partially by TTFB at low concentrations of uncouplers. It was without effect on the uncoupling by PCP, DNP and palmitate. Carboxyatractylate, a specific inhibitor of the ADP/ATP antiporter, was shown to almost completely abolish the uncoupling induced by palmitate and partially by low concentration of TTFB, PCP and DNP. Effects of high concentrations of all these uncouplers as well as of any concentrations of gramicidin proved to be kCh- and carboxyatractilate-insensitive. The data are discussed in terms of the hypothesis on the protein-mediated mechanism of the protonophorous uncoupling. PMID- 7988695 TI - Accumulation of trehalose in Saccharomyces cerevisiae growing on maltose is dependent on the TPS1 gene encoding the UDPglucose-linked trehalose synthase. AB - When yeast strains were cultivated on maltose, the synthesis of trehalose already started in the exponential phase of growth, well before exhaustion of the sugar from the medium. This active pattern of trehalose accumulation was also observed in a maltose constitutive mutant strain growing on glucose. However, this accumulation was completely prevented by deletion of the TPS1 gene coding for the catalytic subunit of the UDPglucose-linked trehalose-6-phosphate synthase, indicating that no alternative pathway for trehalose synthesis exists in yeast. The active pattern of trehalose accumulation seems to be consistent with the finding that trehalose-6-phosphate synthase is more active in strains growing on maltose than on glucose. PMID- 7988696 TI - Monoclonal antibodies against metalloporphyrins. Specificity of interaction with structurally different metalloporphyrins. AB - Monoclonal antibodies against Pd-coproporphyrin I have been obtained. The antibody specificity for free as well as for conjugated Pd-coproporphyrin I is characterized. Affinity constants are estimated for 3 monoclonal antibodies effectively interacting with free Pd-coproporphyrin I. A comparative study on the binding of monoclonal antibodies with analogues and derivatives of Pd coproporphyrin I has revealed that the antigen is mainly located inside the antibody paratope. The protein adjoins complementary to the metalloporphyrin in such a manner that antibodies obtained discern only isomer I, and to some degree, isomer III of coproporphyrin. PMID- 7988697 TI - Cloning of the rat and human prostaglandin F2 alpha receptors and the expression of the rat prostaglandin F2 alpha receptor. AB - We have cloned the FP receptor from rat corpus luteum and human uterus cDNA libraries, respectively. The coding DNA sequence in the rat cDNA is 1101 bp and is similar to the mouse cDNA coding for a receptor protein of 366 amino acids. The human sequence shows a 5 bp deficiency in the 3' region, truncating the coding sequence to 359 amino acids. Northern blot analysis indicates highest expression in the ovary. Cell lines have been established giving stable expression of the FP receptor. Activation of the cloned FP receptor gave an increase in intracellular calcium, indicating signaling via phospholipase C mediated phosphoinositide turnover. Using [3H]PGF2 alpha, binding of PGs showed the rank order of fluprostenol > PhXA70 > PGF2 alpha > or = PhXA85 > PGD2 > PGE2. PMID- 7988698 TI - Import of phosphatidylinositol and phosphatidylcholine into mitochondria of the yeast, Saccharomyces cerevisiae. AB - An in vitro assay was designed to study the import of 3H-labeled phosphatidylinositol and phosphatidylcholine, respectively, from unilamellar vesicles into isolated mitochondria of the yeast, Saccharomyces cerevisiae. Both phospholipids reached the inner mitochondrial membrane. During import they were detected in contact sites between the outer and the inner mitochondrial membrane, supporting the notion that these zones are sites of intramitochondrial phospholipid transport. The uncoupler CCCP, the antibiotic adriamycin, and energy depletion caused by oligomycin and apyrase did not inhibit the transport of phosphatidylinositol and phosphatidylcholine into mitochondria. PMID- 7988699 TI - A point mutation within the ATP-binding site inactivates both catalytic functions of the ATP-dependent protease La (Lon) from Escherichia coli. AB - A point mutant in the ATP-binding motif (GPPGVGK362T) of the ATP-dependent protease La from Escherichia coli was investigated in which the lysine at position 362 was replaced by an alanine. The catalytic efficiency of the K362A mutant is at least two orders of magnitude lower than that of wild-type protease La due to a decreased Vmax and an increased KM for ATP. Simultaneously, the peptidase activity of La K362A is almost completely eliminated. Since selective inactivation of the peptidase activity of La does not affect its intrinsic ATPase activity, coupling of proteolysis with ATP hydrolysis is only uni-directional in this energy-dependent protease. PMID- 7988700 TI - Characterization of energetically functional inverted membrane vesicles from Corynebacterium glutamicum. AB - We show that inverted membrane vesicles from Corynebacterium glutamicum, a Gram positive bacterium, are able to generate and maintain an electrochemical gradient of protons in response to the addition of NADH. This result indicates that the respiratory chain is intact and that the vesicles are reasonably impermeable to protons. These membrane vesicles may be the starting point for in vitro translocation studies of proteins in Gram-positive bacteria. PMID- 7988701 TI - Effect of adrenomedullin on hepatic pericytes (stellate cells) of the rat. AB - When hepatic stellate cells (Ito cells, fat-storing cells) were incubated with adrenomedullin, they underwent relaxation as monitored by the silicone-rubber membrane method; 43%, 65% and 87% of stellate cells relaxed 5, 10 and 20 min, respectively, after addition of 10(-6) M adrenomedullin. Adrenomedullin also triggered the dissociation of F-actin and induced transformation of stellate cells to dendritic cell-like structure. When incubated with 10(-6) M of adrenomedullin for 30 min, cellular levels of cAMP increased from the basal value of 10.2 +/- 1.4 to 107 +/- 2.8 pmol/2 x 10(5) cells without affecting cGMP levels. The reaction occurred dose-dependently and was inhibited by an antagonist of calcitonin gene-related peptide. Adrenomedullin had negligible effects on DNA and protein synthesis in proliferating stellate cells. Thus, adrenomedullin is a potent relaxing peptide to hepatic stellate cells and may contribute to the regulation of sinusoidal microcirculation. PMID- 7988702 TI - Unphosphorylated and tyrosine-phosphorylated forms of a focal adhesion protein, paxillin, are substrates for calpain II in vitro: implications for the possible involvement of calpain II in mitosis-specific degradation of paxillin. AB - Cell-to-substratum adhesion becomes weakened during mitosis of the cell cycle in fibroblasts. The level of one focal adhesion protein, paxillin, is greatly reduced in mitotic-arrested cells. We show here the possible involvement of calpain II, known to be localized in focal adhesion plaques, in the degradation of paxillin. Paxillin is tyrosine-phosphorylated during interphase of the cell cycle by protein tyrosine kinases (PTK) such as c-Src and Csk, and becomes dephosphorylated during mitosis. Our data, however, indicate that tyrosine phosphorylation of paxillin does not affect the rate of paxillin degradation by calpain in vitro. PMID- 7988703 TI - Molecular cloning, expression and chromosomal localisation of human AMP-activated protein kinase. AB - A cDNA encoding rat liver AMP-activated protein kinase (AMPK) was used to isolate human skeletal muscle AMPK cDNA clones. Human AMPK cDNA is more than 90% homologous to the rat sequence and predicts a protein of molecular mass 62.3 kDa, which closely agrees with the mass observed in Western blots of human tissues. AMPK antibodies were also shown to immunoprecipitate AMPK from human liver extracts. A cDNA probe was used to identify a 9.5kb transcript in several human tissues and to isolate human genomic clones. PCR mapping of rodent/human hybrid cell lines localised the human AMPK gene to chromosome 1, and fluorescent in situ hybridisation with a human genomic clone was used to sub-localise the human AMPK gene to 1p31. PMID- 7988704 TI - Transient induction of fatty acid synthase in rat liver after removal of a peroxisome proliferator. AB - Removal of a peroxisome proliferator from the diet triggered the degradation of peroxisomes and induced the transient expression of a 220 kDa soluble protein in rat liver. The 220 kDa protein was purified by conventional methods and analyzed by amino acid sequencing. A total of 99 amino acid residues in 4 lysylendopeptidase-digested peptides completely matched those in rat fatty acid synthase. The transient induction of fatty acid synthase mRNA during peroxisome degradation was confirmed by Northern blotting. PMID- 7988705 TI - Identification of annexin 33 kDa in cultured cells as a binding protein of influenza viruses. AB - The binding of three influenza A and one influenza B virus strains to proteins of three continuously cultured cell lines was studied using protein overlay and immunostaining methods. The results obtained indicated the presence of both sialic acid-dependent and -independent binding of the virus strains; virus binding to proteins in the molecular mass range from about 40 to 103 kDa was dependent on sialic acid, whereas binding to the 33 kDa protein was independent of sialic acid. The 33 kDa binding protein was identified as annexin, a widely distributed non-glycosylated calcium-dependent phospholipid-binding protein. PMID- 7988706 TI - Production and characterization of monoclonal anti-idiotypic antibodies to muramylpeptide. AB - Hybridomas producing monoclonal anti-idiotypic antibodies (anti-id MAbs) to N acetylglucosaminyl-beta 1-4-N-acetylmuramyl-alanyl-D-isoglutamine (GMDP) were developed. Three clones of hybridomas demonstrated the properties characteristic for the Ab2 beta type of anti-id antibody: they bound to Fab-fragments of high affinity MAb to GMDP; dose-dependent inhibition of this binding by GMDP was observed; immunization of mice with these MAbs resulted in production of GMDP specific antibodies. When these antibodies were used to stain blots from SDS-PAGE of macrophage lysate, the same receptor proteins were specifically stained as upon staining with 125I-labelled GMDP derivative. PMID- 7988708 TI - Stereochemistry of the hydrolysis of glycosidic linkage by endo-beta-1,4 xylanases of Trichoderma reesei. AB - Methyl beta-D-xylotrioside was used as a non-reducing substrate to investigate the stereochemistry of hydrolysis of beta-1,4-xylopyranosidic linkage by purified endo-beta-1,4-xylanases (EC 3.2.1.8) of Trichoderma reesei, employing 1H NMR spectroscopy. The fungus produces one acidic species (pI 4.8-5.5), designated as EXI, and one alkaline species (pI 8.5-9.0), designated as EXII. Both enzymes were found to cleave the xylotrioside predominantly to methyl beta-D-xyloside and xylobiose. Monitoring of the intensity of the H-1 signals of alpha- and beta xylobiose during the time course of hydrolysis clearly showed that both enzymes liberate the beta-anomer of xylobiose, i.e. a product with anomeric configuration identical with that of the cleaved glycosidic linkage. This means that both EXI and EXII belong to the so-called retaining glycanases that utilize the double displacement reaction mechanism of hydrolysis. PMID- 7988707 TI - Tyrosine phosphorylation of the MUC1 breast cancer membrane proteins. Cytokine receptor-like molecules. AB - Phosphorylation on tyrosine residues is a key step in signal transduction pathways mediated by membrane proteins. Although it is known that human breast cancer tissue expresses at least 2 MUC1 type 1 membrane proteins (a polymorphic high molecular weight MUC1 glycoprotein that contains a variable number of tandem 20 amino acid repeat units, and the MUC1/Y protein that is not polymorphic and is lacking this repeat array) their function in the development of human breast cancer has remained elusive. Here it is shown that these MUC1 proteins are extensively phosphorylated, that phosphorylation occurs primarily on tyrosine residues and that following phosphorylation the MUC1 proteins may potentially interact with SH2 domain-containing proteins and thereby initiate a signal transduction cascade. As with cytokine receptors, the MUC1 proteins do not harbor intrinsic tyrosine kinase activity yet are tyrosine phosphorylated and the MUC1/Y protein participates in a cell surface heteromeric complex whose formation is mediated by two cytoplasmically located MUC1 cysteine residues. Furthermore, the MUC1/Y protein demonstrates sequence similarity with sequences present in cytokine receptors that are known to be involved in ligand binding. Our results demonstrate that the two MUC1 isoforms are both likely to function in signal transduction pathways and to be intimately linked to the oncogenetic process and suggest that the MUC1/Y protein may act in a similar fashion to cytokine receptors. PMID- 7988709 TI - Purification and characterization of a novel superantigen produced by a clinical isolate of Yersinia pseudotuberculosis. AB - A superantigen designated as Yersinia pseudotuberculosis-derived mitogen (YPM) was purified in an equal manner from both the culture supernatant and cell lysate of a clinical isolate (KUR-1) of Y. pseudotuberculosis serotype 4b. A significant proliferative response of human peripheral blood mononuclear cells to purified YPM was detectable even at a concentration of 1 pg/ml. The N-terminal sequence of YPM which included 23 amino acid residues was determined, by automated Edman degradation, as Thr-Asp-Tyr-Asp-Asn-Thr-Leu-Asn-Ser-Ile-Pro-Ser-Leu-Arg-Ile-Pro Asn-Il e-Ala-Thr-Tyr-Thr-Gly-. This sequence differed from not only all the, hitherto, reported superantigens but also known proteins. While molecular weights of known bacterial superantigens are more than 22,000, electrospray ionization mass spectrometry showed that the molecular weight of YPM was 14524.4. These results indicate that YPM comprises a novel superantigen with substantial structural differences from other bacterial superantigens produced by Gram positive cocci. PMID- 7988710 TI - Histidine-419 plays a role in energy coupling in the vesicular monoamine transporter from rat. AB - Vesicular monoamine transporters (VMAT) catalyze transport of serotonin, dopamine, epinephrine and norepinephrine into subcellular storage organelles in a variety of cells. Accumulation of the neurotransmitter depends on the proton electrochemical gradient across the organelle membrane and involves VMAT-mediated exchange of two lumenal protons with one cytoplasmic amine. It has been suggested in the past that His residues play a role in H+ movement or in its coupling to active transport in H(+)-symporters and antiporters. Indeed VMAT-mediated transport is inhibited by reagents specific for His residues. We have identified one His residue in VMAT1 from rat which is conserved in other vesicular neurotransmitter transporters. Mutagenesis of this His (H419) to either Arg or Cys completely inhibits [3H]serotonin and [3H]dopamine accumulation. Mutagenesis also inhibits other H(+)-dependent partial reactions of VMAT such as the acceleration of binding of the high affinity ligand reserpine, but does not inhibit the [3H]reserpine binding which is not dependent on H+ translocation. It is concluded that His-419 plays a role in energy coupling in r-VMAT1. PMID- 7988711 TI - The molecular structure of the Na(+)-translocating F1F0-ATPase of Acetobacterium woodii, as revealed by electron microscopy, resembles that of H(+)-translocating ATPases. AB - The Na(+)-translocating F1F0-ATPase of Acetobacterium woodii was examined by electron microscopy. After reconstitution into proteoliposomes, knobs typical for the F1 domain were visible on the outside of the membrane. The F1-part of the isolated enzyme showed a hexagonal symmetry suggesting an alpha 3 beta 3 structure, and the F1F0 complex had molecular dimensions very similar to those of H(+)-translocating ATPases of E. coli, chloroplasts, and mitochondria. PMID- 7988712 TI - Transforming growth factor beta 1, insulin and prostaglandin E1 enhance prostaglandin F2 alpha mitogenic action in Swiss 3T3 cells via separate events. AB - Transforming growth factor beta 1 (TGF beta 1) had no mitogenic effect in Swiss 3T3 cells, but could increase prostaglandin F2 alpha (PGF2 alpha)-induced DNA synthesis. Insulin, but not prostaglandin E1 (PGE1), further enhanced PGF2 alpha action at low TGF beta 1 concentrations. TGF beta 1 also acted concertedly with the protein kinase C (PKC) activator 1-oleoyl-2-acetylglycerol to induce mitogenesis. Thus, it appears that TGF beta 1 and insulin act via separate signals, while TGF beta 1 and PGE1 might share a common pathway not involving TGF beta 1-mediated prostaglandin synthesis. These results suggest that TGF beta 1 might elicit various signalling mechanisms to enhance PGF2 alpha-triggered events. PMID- 7988713 TI - Sensory rhodopsin I photocycle intermediate SRI380 contains 13-cis retinal bound via an unprotonated Schiff base. AB - Sensory rhodopsin I (SRI), the mutated derivative SRI-D76N and the complex of SRI with its transducer HtrI were overexpressed in Halobacterium salinarium and analyzed by resonance Raman spectroscopy. In the initial state SRI contains all trans retinal bound via a protonated Schiff base as confirmed by retinal extraction which yields 95 +/- 3% all-trans retinal. The photocycle intermediate absorbing maximally at 380 nm (SRI380) contains a Schiff base linkage between the protein and 13-cis retinal. Extraction of illuminated SRI yields up to 93% 13-cis retinal. Neither the mutation D76N nor HtrI changed the vibrational pattern of the chromophore. PMID- 7988714 TI - Biochemical approaches of increasing thermostability of beta-amylase from Bacillus megaterium B6. AB - Studies on the irreversible thermoinactivation of beta-amylase from Bacillus megaterium B6 exposed to 60 degrees C revealed that the deactivation mechanism probably results from the oxidation of thiols present at the active site of the enzyme. Several attempts were made to increase its thermostability, which indicated that Mn2+ played a key role in determining thermostability and partially reactivating the inactivated enzyme. Immobilization of beta-amylase through gel-entrapment and covalent crosslinking brought about a remarkable increase in thermotolerance with about a 14-fold increase in catalytic half-life. PMID- 7988715 TI - Characterization of the promoters of the guinea pig neutrophil cationic peptide-1 and -2 genes. AB - Guinea pig neutrophils contain the antimicrobial cationic peptides GNCP-1 and GNCP-2 in the granules. To understand the regulation of the gene expression, the promoters for the GNCP-1 and GNCP-2 genes were characterized. Sequencing analysis of the genomic clones showed that the nucleotide sequences of the 5'-upstream regions (1.7 kb) from exon 1 were homologous (90-93%) between the GNCP-1 and GNCP 2 genes. However, transient transfection assays using luciferase reporter gene constructs revealed that the promoter activity of GNCP-1 was 2-fold greater than that of GNCP-2. Furthermore, DNase I footprint analysis demonstrated that three regions (I, II and III) were protected on the GNCP-1 promoter, whereas only two protected regions (II and III) were identified on the GNCP-2 promoter. Together these observations indicate that GNCP-1 and GNCP-2 are encoded by homologous genes, but the expression of the GNCP-1 and GNCP-2 genes is likely to be different at the level of transcription. PMID- 7988716 TI - 5-Hydroxytryptamine affects turnover of polyphosphoinositides in maize and stimulates nitrate reductase in the absence of light. AB - Incubation of etiolated maize leaves for 5 min in 5-hydroxytryptamine increased phosphatidylinositol-4,5-bisphosphate levels but on longer incubation its level decreased and a corresponding increase in inositol-trisphosphate was observed. The increase in phosphatidylinositol-4,5-bisphosphate by 5-hydroxytryptamine was similar to that obtained after short irradiation of leaves with red light. Nitrate-inducible and phytochrome-stimulated enzyme nitrate reductase could be stimulated in darkness if the leaves were incubated in the presence of nitrate and 5-hydroxytryptamine. These results indicate that one of the initial events in phytochrome-mediated enzyme stimulation could be through the generation of 'signals' from the turnover of the phosphoinositide cycle. PMID- 7988717 TI - Changes in the NAD(P)H concentration caused by addition of nitrogenase 'switch off' effectors in Rhodospirillum rubrum G-9, as measured by fluorescence. AB - The effect of nitrogenase 'switch-off' effectors on the concentration of NAD(P)H in Rhodospirillum rubrum G-9 was investigated by fluorescence. A rapid decrease in fluorescence was observed when cells, either N2-grown or nitrogen-starved, were subjected to the effectors, but not when sodium chloride or Tris buffer was added. No effects on the fluorescence were observed in non-nitrogen fixing cultures except when NAD+ was added. The results strongly indicate that the redox state of the pyridine nucleotide pool affects the control of the regulation of nitrogenase activity in R. rubrum. PMID- 7988718 TI - Purification of type 1 protein (serine/threonine) phosphatases by microcystin Sepharose affinity chromatography. AB - A microcystin (MC)-Sepharose column was prepared by addition of 2 aminoethanethiol to the alpha, beta-unsaturated carbonyl of the N methyldehydroalanine residue of MC-LR, followed by reaction of the introduced amino group with N-hydroxysuccinimide-activated CH-Sepharose. The MC-Sepharose bound protein phosphatase-1 (PP1) with high capacity and purified human PP1 gamma in one step from E. coli extracts. It was also used to purify forms of PP1 bound to myofibrils from skeletal muscle. Two of these comprised PP1 complexed to N terminal fragments of the M-subunit which enhance its myosin phosphatase activity, while the third comprised PP1 and an N-terminal fragment of the glycogen-binding (G)-subunit. PMID- 7988719 TI - Identification of multiple, novel, protein kinase C-related gene products. AB - A PCR approach has been employed to screen two cDNA libraries for PKC(-related) sequences. In each case multiple cDNAs were identified, including known PKC isotypes, a previously unknown PKC-eta related sequence and three members of what appears to be a protein kinase C related kinase (PRK 1-3) family. The origin and relationships of these predicted proteins is discussed. PMID- 7988720 TI - Molecular cloning of cDNA encoding the 110 kDa and 21 kDa regulatory subunits of smooth muscle protein phosphatase 1M. AB - The structures of the M110 and M21 regulatory subunits of protein phosphatase-1M, the major enzyme which dephosphorylates myosin in smooth muscle, have been deduced from cloned cDNAs. The N-terminus of the M110 subunit from rat aorta contains seven ankyrin repeats, while the C-terminus of the M21 subunit from chicken gizzard contains a leucine zipper motif. The M110 subunit is expressed in two different forms which differ in their C-terminal sequences. One of these is highly homologous to the whole of the M21 subunit. PMID- 7988721 TI - Blockage of the urokinase receptor on the cell surface: construction and characterization of a hybrid protein consisting of the N-terminal fragment of human urokinase and human albumin. AB - Receptor-bound urokinase is likely to be a crucial determinant in both tumor invasion and angiogenesis. We report here that a yeast-derived genetic conjugate between human serum albumin and the 1-135 N-terminal residues of urokinase (u-PA) competitively inhibits the binding of exogenous and endogenous u-PA to its cell anchored receptor (u-PAR). This hybrid molecule (ATF-HSA) also inhibits in vitro pro-urokinase-dependent plasminogen activation in the presence of u-PAR bearing cells. These effects are probably responsible for the observed in vitro inhibition of tumor cell invasion in a reconstituted basement membrane extract (Matrigel). PMID- 7988722 TI - Retinoic acid induces BDNF responsiveness of sympathetic neurons by alteration of Trk neurotrophin receptor expression. AB - The expression of high affinity neurotrophin receptors (TrkA, TrkB, and TrkC) determines the survival response of different populations of neurons to specific members of the neurotrophin family, including nerve growth factor (NGF), brain derived neurotrophic factor (BDNF), and neurotrophin-3 (NT-3). However, the mechanism which controls the expression of neurotrophin receptors during neuronal development is largely unknown. Here we show that the treatment of the cultured sympathetic neurons from newborn rat superior cervical ganglia (SCG) with retinoic acid (RA), a derivative of vitamin A, suppressed the expression of trkA mRNA and induced the expression of trkB mRNA. Expression of the functional TrkB receptor was confirmed by the emergence of trophic dependence of these neurons on BDNF in the absence of NGF. Differential regulation of trk mRNAs by RA provides a possible model for the establishment of neurotrophin dependence of peripheral neurons. PMID- 7988724 TI - Regulation of low density lipoprotein receptor activity in Chinese hamster ovary cells transfected with the c-fms gene. AB - Chinese hamster ovary (CHO) cells were transfected with the human c-fms gene, which encodes the receptor for macrophage colony-stimulating factor, to examine the effects on the low density lipoprotein (LDL) receptor activity. Degradation of [125I]LDL was significantly reduced in the transfected CHO cells as compared to non-transfected cells when incubated in lipoprotein-deficient serum. Quantitative analysis of LDL receptor mRNA using a competitive PCR method demonstrated that LDL receptor suppression occurred at transcription. These findings suggest that expression of the c-fms gene is involved in the regulation of LDL receptors on macrophages. PMID- 7988723 TI - Surface labeling of key residues during assembly of the transmembrane pore formed by staphylococcal alpha-hemolysin. AB - Structural changes in staphylococcal alpha-hemolysin (alpha HL) that occur during oligomerization and pore formation on membranes have been examined by using a simple gel-shift assay to determine the rate of modification of key single cysteine mutants with the hydrophilic sulfhydryl reagent, 4-acetamido-4' ((iodoacetyl)amino)stilbene-2,2'-disulfonate (IASD). The central glycine-rich loop of alpha HL lines the lumen of the transmembrane channel. A residue in the loop remains accessible to IASD after assembly, in keeping with the ability of the pore to pass molecules of approximately 1000 Da. By contrast, residues near the N-terminus, which are critical for pore function, become deeply buried during oligomerization, while a residue at the extreme C-terminus increases in reactivity after assembly, consistent with a location in the part of the pore that projects from the surface of the lipid bilayer. PMID- 7988725 TI - Hepatic glutaminase mRNA is confined to part of the urea cycle domain in the adult rodent liver lobule. AB - This in situ hybridization study describes the developmental appearance of the lobular distribution of the mRNA encoding hepatic glutaminase in normal rat liver. Glutaminase has been proposed to provide the urea cycle with ammonia [Haussinger and Gerok (1983) Eur. J. Biochem. 133, 269-275]. Hence, the (developmental) pattern of expression of the mRNA would be expected to be closely linked to that of the urea cycle enzymes. From embryonic day 20 onward, hepatic glutaminase mRNA can be detected along the entire porto-central axis, with predominant expression in the portal area. In the adult phenotype, which is acquired at the end of the first postnatal week, glutaminase mRNA is no longer present along the entire porto-central distance but has become confined to a relatively small periportal domain in which the expression decreases in a porto central direction. Thus, in contrast to the large periportal domain, in which the urea cycle enzymes are expressed, the glutaminase mRNA-expressing domain is much smaller and not contiguous with the glutamine synthase mRNA-expressing pericentral domain, leaving a midlobular area that is devoid of glutaminase mRNA. A similar pattern of distribution was found in adult mouse liver. The significance of these observations is that, within the liver lobules, there is an area in which glutaminase is not expressed and, hence, glutamine can not be the substrate for urea synthesis. PMID- 7988727 TI - Interleukin-10 and pentoxifylline inhibit C-reactive protein-induced tissue factor gene expression in peripheral human blood monocytes. AB - Fibrin deposition is an integral feature of the inflammatory response. In response to C-reactive protein (CRP), an acute-phase reactant, blood monocytes synthesize and express tissue factor (TF), the main initiator of blood coagulation. We report the inhibitory effect of interleukin 10 (IL-10) and that of pentoxifylline, a methyl xanthine derivative, on monocyte expression of TF activity, TF protein and TF mRNA in response to CRP. These agents may be of use in diseases where a TF-induced prothrombotic state is detrimental. PMID- 7988726 TI - Adding a positive charge at residue 46 of Drosophila alcohol dehydrogenase increases cofactor specificity for NADP+. AB - We previously reported that the D39N mutant of Drosophila alcohol dehydrogenase (ADH), in which Asp-39 is replaced with asparagine, has a 60-fold increase in affinity for NADP+ and a 1.5-fold increase in kcat compared to wild-type ADH [Chen et al. (1991) Eur. J. Biochem. 202, 263-267] and proposed that this part of ADH is close to the 2'-phosphate on the ribose moiety of NADP+. Here we report the effect of replacing Ala-46 with an argine residue, and A46R mutant, on binding of NADP+ to ADH and its catalytic efficiency with the NADP+ cofactor, and a modeling of the three-dimensional structure of the NAD(+)-binding region of ADH. The A46R mutant has a 2.5-fold lower Km(app)NADP+ and a 3-fold higher kcat with NADP+ compared to wild-type ADH; binding of NAD+ to the mutant was unchanged and kcat with NAD+ was lowered by about 30%. For the A46R mutant, the ratio of kcat/Km of NAD+ to NADP+ is 85, over ten-fold lower than that for wild-type ADH. Our model of the 3D structure of the NAD(+)-binding region of ADH shows that Ala 46 is over 10 A from the ribose moiety of NAD+, which would suggest that there is little interaction between this residue and NAD+ and explain why its mutation to arginine has little effect on NAD+ binding. However, the positive charge at residue 46 can neutralize some of the coulombic repulsion between Asp-39 and the 2'-phosphate on the ribose moiety of NADP+, which would increase its affinity for the A46R mutant. We also constructed a double mutant, D39N/A46R mutant, which we find has a 30-fold lower Km(app)NADP+ and 8-fold higher kcat with NADP+ as a cofactor compared to wild-type ADH; binding of NAD+ to this double mutant was lowered by 5-fold and kcat was increased by 1.5-fold. As a result, kcat/Km for the double mutant was the same for NAD+ and NADP+. The principle effect of the two mutations in ADH is to alter its affinity for the nucleotide cofactor; kcat decreases slightly in A46R with NAD+ and remains unchanged or increases in the other mutants. PMID- 7988728 TI - Interactions of eukaryotic elongation factor 2 with actin: a possible link between protein synthetic machinery and cytoskeleton. AB - Eukaryotic elongation factor 2 (EF-2) was shown to bind to F-actin as assayed by co-sedimentation. In the presence of guanosine-5'-O-(3-thiotriphosphate) (GTP gamma S) binding was increased fourfold. At saturation level a molar ratio of about 0.12 EF-2 per F-actin (subunit) was observed. Our results suggest a single type of binding site with an apparent dissociation constant of 0.85 microM. The stoichiometry was independent of the filament length, and ADP-ribosylation had no effect on the binding. Experimental data indicated the involvement of SH-groups of both EF-2 and actin in the binding. The interaction EF-2 with F-actin appeared to be inhibited competitively by EF-1 alpha and non-competitively by G-actin. PMID- 7988729 TI - Biochemical characterization of glucosaminylmuramyldipeptide binding sites of murine macrophages. AB - By using radioligand analysis, murine peritoneal macrophages were shown to express several hundred high-affinity cell surface GMDP-binding sites (Ka 350 pM). Photoaffinity labeling followed by SDS-PAGE enabled us to identify 32-34 and 38 kDa proteins inside these cells that bound GMDP specifically. PMID- 7988730 TI - Autoantigen Ku protein is involved in DNA binding proteins which recognize the U5 repressive element of human T-cell leukemia virus type I long terminal repeat. AB - We have identified and analyzed a 27-nucleotide sequence (U5 repressive element, designated as U5RE) at the U5 region of the human T-cell leukemia virus type I (HTLV-I) long terminal repeat (LTR) which is required for HTLV-I basal transcriptional repression. The basal promoter strength of constructs that contained deletions in the U5 region of the LTR was analyzed by chloramphenicol acetyltransferase (CAT) assays following transfection of HeLa cells or Jurkat T cells in the presence or absence of viral transactivator tax protein. We consistently observed a 2- to 5-fold increase in basal promoter activity when sequences between +277 to +306 were deleted. In vivo competition experiments suggested that the U5 DNA fragment from +269 to +295 contains a functional repressive element (U5RE). Using gel mobility shift assays, we have purified a highly enriched fraction that could specifically bind U5RE. This DNA affinity column fraction contained three major detectable proteins on sodium dodecyl sulfate-polyacrylamide gel electrophoresis with silver staining: 110-, 80- and 70 kDa proteins. The 110-kDa protein appeared to be a novel DNA-binding protein whose characteristics are still obscure, while the 70- and 80-kDa proteins were shown to be related to the human autoantigen Ku, the Ku (p70/p80) complex, as demonstrated by amino acid sequencing and immunological analyses. As Ku is known to be involved in transcriptional regulation, the specific interaction of Ku with U5RE raises intriguing possibilities for its function in HTLV-I basal transcriptional repression. PMID- 7988731 TI - Transcriptional regulation of environmentally inducible genes in plants by an evolutionary conserved family of G-box binding factors. AB - 1. In reviewing a number of the most intensely studied environmentally inducible promoters it becomes clear that the presence of two cis-acting elements are critical for promoter activity, one of which is the G-box (CCACGTGG). A mutation in one of the two elements abolishes or severely reduces the ability of the promoter to respond to environmental changes. The sequence of the second cis acting element, positioned nearby the G-box, is not conserved among the different inducible promoters, but may be similar among promoters induced by the same signal. The spacing between the G-box and the second cis-acting element appears to be critical, suggesting a direct interaction between the respective binding factors. We speculate on a potential role of the G-box promoter element in the signal induction of promoter activity. 2. From a number of plant species nuclear proteins interacting with the G-box have been identified. Recently, G-box Binding Factors (GBF) have been isolated by screening cDNA expression libraries with a characterized G-box cis-acting element as DNA probe. The deduced amino acid sequence of the GBF clones revealed that they possess the features of the basic leucine zipper class of trans-acting factors. By amino acid sequence comparison and limited mutational analysis, we define amino acids critical for G-box binding specificity. All GBFs isolated to date have a conserved proline-rich domain involved in transcriptional activation. A number of GBFs are inducible by a particular environmental signal. 3. Recently, a protein designated GF14 has been isolated that is associated with the GBF protein complex. The protein has homology to mammalian brain specific proteins, which seem to function as regulators of phosphorylation events. GBF activity is regulated by phosphorylation. The GF14 proteins may therefore impose an additional control on gene expression. PMID- 7988732 TI - Net glucose production from acetone in isolated murine hepatocytes. The effect of different pretreatments of mice. AB - 1. To evaluate the condition under which net glucose production from acetone, added as sole substrate, occurs different pretreatments of mice, in combination with starvation, were used; (i) acetone pretreatment (acetone is a known inducer of cytochrome P-450 isozymes involved in this pathway), (ii) fructose pretreatment (to induce NADPH+H+ generating enzymes) or (iii) their combination. 2. There was net glucose formation from acetone only in that case, when the cells were prepared from 48 hr fasted animals pretreated with both acetone and fructose. However, using 2-14C-acetone, incorporation of 14C-carbon into glucose could be detected in all the cases and, at the same time, acetone was without any effect on protein synthesis. 3. The addition of acetone increased gluconeogenesis from alanine in almost all the cases. The only exception from this general rule was that the case, when hepatocytes were prepared from acetone pretreated 48 hr starved mice where, instead of the elevation of glucose formation, a decrease of that was caused by acetone. 4. Acetone decreased 14C-carbon incorporation into glucose from 14C-(U)-alanine added at saturating concentration in hepatocytes prepared from starved mice. 5. Similarly to acetone there was no net glucose formation from acetone either when added alone, however, it enhanced gluconeogenesis from alanine at non-saturating concentrations of the amino acid. 6. Methylglyoxal proved gluconeogenic in all the cases. 7. It is concluded that net glucose formation from acetone as sole substrate occurs only under those conditions which are far from a physiological situation, however, when gluconeogenesis from another substrate takes place, acetone can contribute to net glucose formation in hepatocytes prepared from fasted mice. PMID- 7988733 TI - Different oxidative pathways of isonicotinic acid hydrazide and its meta-isomer, nicotinic acid hydrazide. AB - 1. Superoxide was generated during the auto-oxidation of the antituberculous drug, isonicotinic acid hydrazide (INH), but not with its meta-isomer, nicotinic acid hydrazide (NH). During Fe(3+)-stimulated oxidation of INH and NH, aromatic hydroxylation occurred which was inhibited by the chelating agent, phytic acid. 2. A mixture of myeloperoxidase (MPO) and a hydrazide induced formation of compound III (oxyperoxidase) and aromatic hydroxylation which was stimulated by phytic acid. INH was considerably more potent than NH. 3. Co-oxidation of a hydrazide and thyroxine (T4) in the MPO system resulted in the formation of a pink-coloured product (maximum absorbance at 504 nm) which was more stable with NH than with INH. 4. The hydrazides and Cl- acted synergistically on MPO haem modification when co-oxidised in the MPO-H2O2 system. INH was more destructive than NH. 5. The different oxidative pathways of the hydrazides are consistent with the fact that an acyl intermediate of INH, unlike that of NH, is resonance stabilized. PMID- 7988734 TI - Activation of 3-methyl-branched fatty acids in rat liver. AB - 1. Subcellular fractionation of rat liver revealed that 3-methylmargaric acid, a monobranched phytanic acid analogue, can be activated by mitochondria, endoplasmic reticulum and peroxisomes. 2. Indirect data (effects of pyrophosphate and Triton X-100) suggested that the peroxisomal activation of 3-methylmargaric, 2-methylpalmitic and palmitic acid is catalyzed by different enzymes. 3. Despite many attempts, column chromatography of solubilized peroxisomal membrane proteins so far did not provide more conclusive data. On various matrices, lignoceroyl-CoA synthetase clearly eluted differently from the synthetases acting on 3 methylmargaric, 2-methylpalmitic and palmitic acid. The latter three however, tended to coelute together, although often not in an identical manner. PMID- 7988735 TI - Spectral analysis of Fe(III)-complex reduction by hemoglobin: possible mechanisms of interaction. AB - 1. Hemoglobin is capable of electron transfer to Fe(III)-complexes of ATP, EDTA, NTA, and citrate leading to formation of reduced Fe(II) and its concurrent release from these chelating compounds as evident in the formation of a Fe(II) Tris 2,2' bipyridine complex. 2. Multi-component analysis of kinetic spectra in the visible region (700-500 nm) has permitted a determination of the effect of various chelating molecules bound to Fe(III), pH, the effects of ionic strength, temperature, and the molecular nature of the Fe(III)-complex on reaction rates. 3. We have examined and compared the reactivities of normal adult hemoglobin A (alpha 2 beta 2) to reduce these Fe(III)-complexes and suggest possible mechanism(s) for the electron transfer process. PMID- 7988736 TI - Effect of methyl methacrylate on mitochondrial function and structure. AB - 1. Treatment of isolated rat liver mitochondria with methyl methacrylate (MM) produced membrane disruption as evidenced by the release of citrate synthase, and changes in the ultrastructure of mitochondria. 2. At concentration 0.1%, MM uncoupled oxidative phosphorylation as evidenced by stimulation of state 4 respiration supported either by pyruvate plus malate or succinate (+rotenone) and ATP-ase activity in intact mitochondria. 3. At concentration 1% MM stimulated ATP ase activity in intact mitochondria and succinate (+ rotenone) oxidation at state 4 and was without effect on this substrate oxidation at state 3. 4. MM inhibited pyruvate plus malate oxidation either at state 3 or in the presence of uncoupling agents. 5. MM inhibited the NADH oxidase of electron transport particles at a concentration which failed to inhibit either succinic oxidase or the NADH ferricyanide reductase activity. 6. The data presented suggest that in the isolated mitochondria MM inhibits NADH oxidation in the vicinity of the rotenone sensitive site of complex I. 7. The general conclusion is that MM may block an electron transport and to uncouple oxidative phosphorylation in rat liver mitochondria. The overall in vitro effect would be to prevent ATP synthesis which could result in cell death under in vivo conditions. PMID- 7988737 TI - Solubilization, partial purification and functional reconstitution of a sheep brain endoplasmic reticulum anion channel. AB - 1. An intracellular anion channel, known to be co-localized in brain endoplasmic reticulum membranes with ryanodine-sensitive calcium-release channels, was incorporated into voltage-clamped planar lipid bilayers from sheep brain microsomal membrane vesicles. 2. Single channels, which displayed a main open state conductance of 80-100 pS in symmetric 450 mM choline Cl, reduced to approximately 20 pS in symmetric 225 mM (choline)2SO4 (the solutions also contained 10 mM Tris-HCl, pH 7.4), discriminated poorly between Cl- and choline+ (relative permeability ratio, PCl-/Pcholine+, 2.5). 3. Sheep brain microsomal membrane proteins were solubilized in the zwitterionic detergent CHAPS, and subjected to sequential anion-exchange and size-exclusion chromatography; the solubilizate, and partially-purified protein fractions, were then incorporated into large unilamellar liposomes by freeze-thaw sonication. 4. Reconstituted passive anion (Cl-)-transport, which was reduced by approximately 60% in the presence of SO4(2-), was assayed by measuring the efflux of entrapped 36Cl- (compared to the efflux of [3H]inulin), and also by monitoring the fluorescence quenching of entrapped SPQ by Cl(-)-influx. 5. Cl(-)-transporting activity was enriched up to 200-fold after two stages of purification, and the partially purified channel protein was incorporated from reconstituted proteoliposomes into planar lipid bilayers, where its permeation behaviour remained very similar to that observed for the native channel. PMID- 7988738 TI - Tissue lipoperoxidation and glutathione peroxidase activity in puromycin aminonucleoside injected rats. AB - 1. Lipoperoxidation (LPx) and glutathione peroxidase (GPx) activity were measured in kidney, liver, heart, lung, brain and testis from control and puromycin aminonucleoside (PAN) injected rats on days 1-6, 8, 10, 16 and 22 after vehicle or PAN injection. 2. PAN-injected rats developed proteinuria on day 3. 3. In PAN injected rats: (a) LPx increased in kidney, liver, lung, brain and testis before day 3 and in heart on day 3; (b) GPx activity increased in kidney, liver, heart, lung and testis and diminished in brain on day 3 or after. PMID- 7988739 TI - DNase-I-like enzyme from the carp liver--inhibition by muscle and endogenous actin. AB - 1. DNase-I-like activity occurs in the carp (Cyprinus carpio) liver cytosol (supernatant 105,000 g). 2. The enzyme resembles DNase I from bovine pancreas in respect to the molecular mass (approximately 31 kDa), pH (7.4) and ion requirements (Mg2+, Ca2+) and the ability to degrade native as well as denatured DNA. 3. As judged by comparison of DNase zymograms obtained after native- and SDS PAGE, the enzyme occurs in the three molecular forms of similar molecular weight and different charges. 4. All these forms are inhibited by rabbit skeletal muscle actin as well as by endogenous actin isolated from the carp liver cytosol. 5. DNase from the carp liver cytosol does not interact with the antibodies directed against DNase I from bovine pancreas and against DNase I from the rat and bovine parotid glands. PMID- 7988740 TI - Platelet-activating factor acetylhydrolase (PAF-AH) in human kidney. AB - 1. PAF-AH activity in human kidney (cortex and medulla) has been demonstrated and shares the following properties. 2. Does not require the presence of Ca2+ and appears to be different from phospholipase A2. 3. The pH optimum shows a peak at 7-7.4. 4. It is stable for 4 days at -30 degrees C. 5. It is mainly distributed in the microsomal fraction. 6. The apparent Km values of the enzymes of cortex and medulla are 0.553 and 0.207 microM, respectively and distinct from serum PAF AH (1.439 microM). 7. The apparent molecular weight values are 60,000 and 25,000 for medulla and cortex, respectively and distinct from serum PAF-AH (94,000). PMID- 7988741 TI - The sequence of porcine 80 kDa 17 beta-estradiol dehydrogenase reveals similarities to the short chain alcohol dehydrogenase family, to actin binding motifs and to sterol carrier protein 2. AB - The cDNA of porcine 17 beta-estradiol dehydrogenase codes for a polypeptide of 737 amino acids. The dehydrogenase activity of the 80 kDa translation product is located in its N-terminal 32 kDa fragment, which is the major form isolated from endometrial epithelium. beta-Actin co-purifies with some of the 32 kDa enzyme, which contains actin-binding motifs and is homologous to hydratase-dehydrogenase epimerase of Candida tropicalis. The microbody-targeting signal AKI and sequences resembling sterol carrier protein 2 are present in the C-terminal part of the 80 kDa protein. The N- and C-terminal parts are connected by a sequence containing the putative protease recognition signal AAP. PMID- 7988743 TI - Linkage analysis does not support a role for glucokinase gene in the aetiology of type 2 diabetes mellitus among north western Italians. AB - The contribution of a 3' glucokinase gene polymorphism to the aetiology of type 2 diabetes mellitus was studied in 17 diabetic pedigrees from North-Western Italy; linkage methodology was used. A CA repeat sequence was employed as a marker and amplified by PCR. Three alleles were found: Z (195 bp), Z + 4 (199 bp) and Z + 10 (205 bp). Since in diabetic families linkage analysis gave values of LOD score between -0.000438 and 0.026, the association between GK polymorphism and type 2 diabetes could not be either excluded or accepted. Based on these data, we conclude that glucokinase polymorphism is not a major determinant of type 2 diabetes mellitus, at least in our population, but, consistent with LOD score obtained, in some pedigrees it could assume a minor role in the aetiology of this disease. PMID- 7988742 TI - Insulin-like growth factor-I stimulates c-fos and c-jun transcription in PC12 cells. AB - We analyzed the effects of insulin-like growth factor-I (IGF-I), a polypeptide growth factor which exerts mitogenic effects via specific membrane receptors. The control of IGF-I on c-fos and c-jun transcription was studied in PC12 cells. Gel mobility shift assays with a labeled AP1 consensus binding sequence (TRE: TGACTCA) showed an increase in specific binding upon trIGF-treatment. Gene transfer studies revealed that the increase in AP1 binding is functional since IGF-I stimulates transcription from a reporter gene containing the minimal TRE linked to the chloramphenicol acetyl transferase (CAT) reporter gene. To further characterize the molecular mechanism by which IGF-I increases AP1 activity, we analysed the transcription regulation of c-fos and c-jun using reporter genes containing the respective promoters or specific regulatory elements. Deletion studies with the c-jun promoter, showed that IGF-I stimulates c-jun transcription via a cis acting element(s) localized within the 132 base pairs prior to the transcription start site; possibly the AP1 like element TGACATCA. Similar studies revealed that c-fos stimulation by IGF-I requires the presence of a regulatory sequence spanning the dyad symmetry element (DSE) and the fos AP1-like sequence (FAP). Further experiments using specific elements linked to the minimal unresponsive c-fos promoter, showed that the DSE is the main target for c-fos induction by IGF-I. PMID- 7988744 TI - The C-terminal half of the porcine estradiol receptor contains no post translational modification: determination of the primary structure. AB - The C-terminal part of ligand filled porcine estradiol receptor extending from H267 to I595 was isolated by adsorption to the monoclonal antibody 13H2, subjected to cleavage by CNBr, o-iodosobenzoic acid and endopeptidase Lys-C as well as other proteases, both in the native and the denatured state. The overlapping peptides produced were separated by reverse phase HPLC and sequenced by Edman degradation, lacking T570-M581 in domain F. We found no evidence of post translational modification; the native fragment is not glycosylated and the tyrosyl residues in domain E (aa 328, 331, 459, 526, 537) and F (aa 582, 583) are not phosphorylated. In addition, all serine and threonine PTH derivatives were obtained in normal yields. The amino acid sequence of the fragment corresponds in full with that derived from the cDNA. The complete cDNA-derived sequence codes for a polypeptide of 595 amino acids with a calculated mass of 66,357 Da. The high degree of homology between species in domains C and E is shared by the porcine receptor. PMID- 7988745 TI - Modulation of hepatocyte growth factor gene expression by estrogen in mouse ovary. AB - Hepatocyte growth factor (HGF) is expressed in a variety of tissues and cell types under normal conditions and in response to various stimuli such as tissue injury. In the present study, we demonstrate that the transcription of the HGF gene is stimulated by estrogen in mouse ovary. A single injection of 17 beta estradiol results in a dramatic and transient elevation of the levels of mouse HGF mRNA. Sequence analysis has found that two putative estrogen responsive elements (ERE) reside at -872 in the 5'-flanking region and at +511 in the first intron, respectively, of the mouse HGF gene. To test whether these ERE elements are responsible for estrogen induction of HGF gene expression, chimeric plasmids containing variable regions of the 5'-flanking sequence of HGF gene and the coding region for chloramphenicol acetyltransferase (CAT) gene were transiently transfected into both human endometrial carcinoma RL 95-2 cells and mouse fibroblast NIH 3T3 cells to assess hormone responsiveness. Transfection results indicate that the ERE elements of the mouse HGF gene can confer estrogen action to either homologous or heterologous promoters. Nuclear protein extracts either from RL95-2 cells transfected with the estrogen receptor expression vector or from mouse liver bound in vitro to ERE elements specifically, as shown by band shift assay. Therefore, our results demonstrate that the HGF gene is transcriptionally regulated by estrogen in mouse ovary; and such regulation is mediated via a direct interaction of the estrogen receptor complex with cis acting ERE elements identified in the mouse HGF gene. PMID- 7988746 TI - Expression of short and long forms of prolactin receptor in murine lymphoid tissues. AB - Two different forms of the prolactin receptor, differing in the length of their cytoplasmic domains, have been characterized in many tissues of rodents. To better understand whether short and long forms of PRLR are involved in the immune effects of PRL, we evaluated the distribution of these different forms in the thymus, spleen, lymph nodes and bone marrow from rats and mice. Total RNA was used for cDNA synthesis which was amplified by PCR, using oligonucleotides specific to the different forms of the prolactin receptor. We detected transcripts encoding both forms of prolactin receptor in all lymphoid tissues examined in mouse and rat. Finally we studied the transcript encoding prolactin itself in these rodent tissues; a clear signal was only found in rat thymus. The ubiquitous presence of both forms of receptor transcripts in different lymphoid tissues points to an important role of the PRLR and suggests that such forms of the receptor may be involved in differential functions in lymphocytes. PMID- 7988747 TI - Retinoids are positive effectors of adipose cell differentiation. AB - Retinoids, especially all-trans retinoic acid (t-RA), have been reported in the last decade to inhibit the differentiation of preadipose cells. In those studies, however, the concentrations of t-RA were supraphysiological (0.1-10 microM range). In contrast we show that, when present at concentrations below or close to the Kd values of retinoic acid receptors, retinoids behave as potent adipogenic hormones (1 pM to 10 nM range). As shown by the use of specific ligands for each RAR subtype, these positive effects on adipose differentiation involve in particular the RAR alpha subtype, and have been observed in Ob17 cells exposed to serum-supplemented or serum-free medium, and in rat preadipocytes exposed to serum-free medium. Among the two classes of retinoid acid receptors (RARs) and retinoid X receptors (RXRs), RAR alpha, RAR gamma, RXR alpha and RXR beta mRNAs could be detected in growing adipoblasts and were found to be increased in committed preadipocytes and differentiated cells upon retinoid treatment. Like other adipogenic hormones, retinoids were only effective in the terminal differentiation process leading from preadipocytes to adipocytes. PMID- 7988748 TI - Rat seminiferous tubular culture medium contains a biological factor that inhibits Leydig cell steroidogenesis: its purification and mechanism of action. AB - Seminiferous tubules prepared from adult rats cultured for 48 h in serum-free conditions produce multiple biological factors that modulate Leydig cell steroidogenic function in vitro. Using gel filtration chromatography, it was shown that seminiferous tubular culture medium (STCM) contained at least three inhibitory activities designated AI, AII, and AIII that inhibited testosterone production by purified Leydig cells. The factor that induced AIII activity, designated Leydig cell inhibitor (LCI), was further purified to apparent homogeneity by sequential HPLC using gel permeation, C8-, C18-, C2/C18-reversed phase, and microbore anion exchange columns. When this batch of purified factor was resolved by SDS-PAGE under reducing conditions, only a single silver stained band with an apparent M(r) of 21,000 was detected. Protein sequence analysis using about 100 pmol of purified LCI revealed that its N-terminus was blocked. Incubation of this highly purified factor with Percoll gradient purified Leydig cells induced a dose-dependent inhibition of hCG-stimulated testosterone production. LCI inhibited the basal testosterone production and hCG-stimulated cAMP production by Leydig cell dose-dependently. It also inhibited the forskolin- and cholera toxin-stimulated testosterone and cAMP production but had no apparent effect on the binding of 125I-labeled hCG to LH receptors. These data suggest that this LCI exerts its inhibitory action at steps beyond the LH receptors but prior to the cAMP formation by affecting the adenylate cyclase activity directly or indirectly through inhibition of the stimulatory G-protein (Gs-protein); however, it is also possible that it decreases the coupling of the receptors to the Gs-protein. LCI also inhibited the conversion of exogenously added 22R hydroxycholesterol, pregnenolone, progesterone, and 17 alpha-hydroxyprogesterone to testosterone. However, it had no effect on the conversion of dehydroepiandrostenedione and androstenedione to testosterone. These data strongly suggest that LCI affects the steroidogenic enzymes metabolizing cholesterol to testosterone, the cytochrome P-450 side-chain cleavage (P-450SCC), and cytochrome P-450 17 alpha-hydroxylase/17,20-lyase (P-450C17). However, it has no effect on the 3 beta-hydroxysteroid dehydrogenase (3 beta-HSD) and 17 beta hydroxysteroid dehydrogenase (17 beta-HSD) enzyme activities. Based on the results of the present study, it is apparent that this LCI is distinct from other known potent Leydig cells inhibitors such as interleukin-1 (IL-1) and transforming growth factor-beta (TGF-beta). The LCI appears to involve in the paracrine regulation of Leydig cell function. PMID- 7988749 TI - Agents that increase phosphatidic acid inhibit the LH-induced testosterone production. AB - The results of the present study point to phosphatidic acid (PtdOH) as a possible intracellular messenger, which might be involved in local modulation of testicular testosterone production in vivo. Propranolol (27-266 microM) induced an increased level of [3H]PtdOH in isolated rat Leydig cells, prelabeled with [3H]myristate, and at the same time a strong dose-dependent inhibition of the acute testosterone production stimulated by luteinizing hormone (LH). The inhibition was not bypassed by the addition of dibutyryl-cAMP but was overcome, when 22(R)-hydroxycholesterol was added as a direct substrate for cytochrome P 450 side chain cleavage enzyme. Thus, the inhibition appears to be exerted at a point distal to cAMP-generation but before the first enzyme in the testosterone synthetic pathway. Treatment with other agents (4 beta-phorbol 12-myristate 13 acetate (PMA), A23187, and sphingosine) giving rise to increases in the PtdOH level resulted in the inhibition of the LH-induced testosterone formation as well, thus indicating a connection between the two effects. Furthermore, we were able to demonstrate a highly significant correlation between the PtdOH-increase and the inhibition of the LH-stimulated testosterone production. This may suggest a causal relationship between these two parameters. PMID- 7988750 TI - The cell surface progesterone receptor which stimulates calcium influx in human sperm is unlike the A ring reduced steroid site on the GABAA receptor/chloride channel. AB - Progesterone elicits a rapid, transient calcium influx in sperm that is a prerequisite for the progesterone-induced acrosome reaction. The possibility that the GABAA receptor/chloride channel was the receptor that mediated the progesterone-induced calcium influx in human sperm was examined. A-ring reduced 3 alpha-hydroxy pregnane steroids (e.g. alfaxalone, allopregnanolone, pregnanolone), which are active on the GABAA receptor/chloride channel, were found to be much weaker than progesterone at stimulating Ca2+ influx in sperm. The effects of a variety of progesterone metabolites and analogs and other steroids were compared for their ability to (i) stimulate GABA-induced 36Cl- uptake in synaptoneurosomes, (ii) stimulate GABA-induced Cl- currents in HEK-293 cells transfected with alpha 1, beta 2, and gamma 2 subunits of the GABAA receptor/chloride complex, and (iii) elicit a rapid Ca2+ influx in sperm. No correlation was observed between the ability of a given steroid to stimulate Ca2+ influx and efficacy in eliciting either 36Cl- uptake or chloride currents. Importantly, the action of progesterone to stimulate Ca2+ influx was not modified by GABA, diazepam, picrotoxin and pentobarbitol (known regulators of the GABAA receptor/chloride channel). It is concluded from these studies that the cell surface progesterone binding site on human sperm that mediates progesterone induced changes in [Ca2+]i is unlike the steroid binding site on the GABAA receptor/chloride channel.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7988752 TI - Effect of Griffith precracks on measurement of composite fracture toughness. AB - The objective of this study was to produce true Griffith-type cracks in composite specimens for measuring fracture toughness. A compact test specimen geometry, conforming to the ASTM standard (E-399-84) was chosen for the evaluation. Five methods of precracking were evaluated: 1) placing no precrack (notch in specimen left blunt); 2) placing a sharp notch with a Bard Parker blade under hand pressure; 3) placing a sharp notch with a Bard Parker blade under hand pressure, followed by stressing the sample at 60% of the failure load for 25 cycles; 4) forming a sharp notch by placing a razor blade in the sample during polymerization; and 5) placing a Griffith-type crack. Results indicate that the method of precracking a sample does have a significant effect on the measured value of the fracture toughness. PMID- 7988751 TI - Stability of radicals in cured composite materials. AB - During the radical polymerization of dental composites, the monomers polymerize to form a three-dimensional network containing remaining double bonds and free radicals. At 37 degrees C, these radicals decompose logarithmically with a half life of 2-5 d. In this study, the half-life of radicals in a light-cured inlay composite was determined at different temperatures, and the influence of different fillers and filler amounts on the stability of these radicals in light cured experimental composites was investigated. There is a strong logarithmic relationship between the half-life of the radicals and temperature. At a constant temperature, the half-life of radicals depends on the type of filler, the filler fraction, and the filler surface treatment. The stability of radicals determines to a great extend the adhesion of one composite to another, such as the adhesion of a luting cement to an inlay material. PMID- 7988753 TI - Color mixing in dental porcelain. AB - For esthetic reasons, pigments and opacifiers are added to porcelains used in restorative dentistry. The purpose of this study was to use Kubelka-Munk theory (Kubelka and Munk, 1931) to predict and analyse the colors of porcelains modified by the addition of two pigments and an opacifying agent. The base porcelain was composed of 88% potassium feldspar, 6% quartz and 6% kaolin. The porcelain was modified by the addition of a yellow (Pr-Zr-Si) or a brown (Fe-Cr-Zn) stain and an opacifier (10% SnO in base porcelain). After firing at 1200 degrees C for 30 min, reflectance spectra of the various combinations were obtained with a spectrophotometer. Reflectance spectra, except at low wavelengths, were influenced by increased scattering due to the addition of the opacifier. Calculated values from Kubelka-Munk theory for absorption coefficients and scattering coefficients with appropriate correction factors were compared with the values from the reflectance spectra of the combinations. In general, good agreement was obtained if the scattering coefficient of the opacifier is set equal to 1.0. Using the L*a*b* transform of the CIE color space, it was found that this transform provided uniform color intervals for equal changes in pigment concentration. PMID- 7988754 TI - Anodic polarization behavior and microstructure of a gallium-based alloy. AB - A gallium-based alloy (GA) that was developed as a substitute for dental amalgam was investigated for anodic polarization behavior in deoxygenated Ringers solution, 37 degrees C. The related microstructures were examined and microanalyses were conducted. Four polarization tests were conducted by scanning from -300mV to +1,000 mV (vs. SCE) at 2 mV/s. Polarization of the first sample (GA-1) was stopped after the first anodic dissolution peak (-100 mV, 1.5-2.0 x 10(-3) A/cm2). The fourth sample (GA-4) was interrupted at the secondary peak (+1000 mV, 0.3 A/cm2). It was found that (1) the early stage of the first peak is related to selective dissolution of divalent tin ions, followed by a dissolution of Ga. Transmission electron diffraction (TED) identified the brown corrosion product as Ga2O3; (2) the GA-4 sample was covered with the white corrosion product of mainly Sn+4, identified as SnO2. In addition, the current density of the GA sample when coupled with a high-copper dental amalgam was 0.03 A/cm2 (with +1,000 mV) at the second peak which was about a ten times lower value than for the uncoupled sample; (3) the uncoupled gallium alloy and gallium alloy coupled with a high-copper dental amalgam showed 10(3)-10(4) times higher anodic current density than that of an uncoupled high-copper dental amalgam, suggesting that the gallium alloy is more corrosion prone. PMID- 7988755 TI - The strengthening mechanism of a magnesia core ceramic. AB - A high-expansion core material containing magnesia and forsterite may be used to make all-ceramic dental crowns with porcelain-fused-to-metal body porcelains. The purpose of this study was to investigate the strengthening mechanism for the magnesia core material. Six batches of the magnesia core material were made by reacting magnesia with a silica glass with holding times ranging from 17 to 120 min. The flexural strength was measured using three-point loading according to the ISO specification for dental ceramics. The forsterite content was measured using quantitative x-ray diffraction. A statistically significant correlation was found between the forsterite content and flexural strength. The proposed mechanism for strengthening is the precipitation of fine forsterite crystals in the glass matrix surrounding unreacted magnesia. Longer reaction times produced more dissolution of magnesia and subsequent precipitation of forsterite. This method results in a new strengthening mechanism for dental ceramics which have previously relied on the incorporation of alumina, leucite or ceramic whiskers. PMID- 7988756 TI - Effects of two amine reducing agents on the degree of conversion and physical properties of an unfilled light-cured resin. AB - The influence of varying concentrations of two amine reducing agents commonly used in commercial light-cured composites, N,N-dimethyl-p-toluidine (DMPT) and 2 (N,N-dimethylamino)ethyl methacrylate (DMAEMA), on the degree of conversion (DC), Knoop hardness, and compressive and transverse strengths of an unfilled light cured resin was investigated. The DC obtained from employing two different internal standard peaks, carbonyl (C=O) at 1730 cm-1 and urethane (N-H) at 3350 cm-1, was compared. The resin consisted of 50 wt% triethyleneglycol dimethacrylate (TEGDMA) and 50 wt% 1,6-bis(methacryloxy-2-ethoxycarbonylamino) 2,4,4-trimeth ylhexane (UDMA) activated with 0.5 mol% camphorquinone (CQ) and varying concentrations of either DMPT or DMAEMA. The DC calculated by use of either C=O or N-H absorption peak as an internal reference showed similar values. For both amines, the physical properties were directly related to DC and appeared to reach maximal values at an amine/CQ molar ratio of 4.0. The DC, however, appeared to reach a maximum at an amine/CQ molar ratio of 3.0. Generally, for the same amine/CQ molar ratios, the polymers formulated with DMAEMA, had greater DCs and better physical properties than those formulated with DMPT. PMID- 7988757 TI - Surface analysis of nickel-chromium dental alloys. AB - In this study, the surface compositions of four commercially available nickel chromium alloys, Neptune, Rexalloy, Regalloy T, and Vera Bond, were compared and correlated to the alloys' corrosion behavior. The alloys were chosen to be representative of alloys with acceptable and unacceptable Cr levels, with and without Be additions. The results showed that the non-Be-containing alloys exhibited a homogeneous Cr-Mo oxide surface which resulted in more corrosion resistant alloys. The Be-containing alloys were shown to have non-uniform oxide surfaces. Areas on the surfaces of these alloys were low in Cr and O and enriched in Be. The oxide surfaces of these alloys were more easily disrupted and provided little resistance to accelerated corrosion processes. Thus, it was found that not only were the Cr and Mo content of the alloys important for corrosion resistance, but the composition of the surface oxide as well. PMID- 7988758 TI - Mechanical fatigue of a feldspathic dental procelain. AB - Ceramics are known to undergo chemical static fatigue in the presence of moisture at ambient temperatures. However, until recently, it has been assumed that ceramic materials do not undergo mechanical fatigue. This study, using an indentation technique, demonstrated the existence of mechanically induced cyclic fatigue in a feldspathic dental porcelain under ambient conditions. Growth rates (dc/dN) were consistent with the Paris Law, which is a power law function of the applied stress intensity range (delta K) governing mechanical fatigue phenomena. A Paris exponent m of the order of 4, and a constant C of the order of 2 x 10(-6) were calculated. The susceptibilities of a range of dental ceramics to mechanical fatigue, and the possible interaction between mechanical and chemical static fatigue must be investigated so that materials and techniques giving ceramic prostheses the longest possible lifetimes can be identified. PMID- 7988759 TI - Atomic force microscopy of acid effects on dentin. AB - Atomic force microscopy (AFM) was used in the examination of the early stages of acid treatment of dentin. Disks of highly polished dentin were initially examined under deionized water and following exposure to 0.025 M nitric acid for 20 s intervals from 0-100 s. Peritubular depth changes were linear (0.005 microns/s). The intertubular dentin surface initially moved at approximately 1/2 the peritubular rate and then reached a plateau as the demineralized collagen scaffold collapsed. There was no apparent difference in the tubule center-to center distance during the treatment. Differences in the movement and morphology of the zones are of importance in dentin bonding applications relying on penetration of the demineralized dentin by adhesive monomers. The changes are probably related to the partial collapse of the collagen matrix. Alternatively, access to the apatite crystals and solubility may be higher in the peritubular zone. AFM appears to hold exceptional promise for the study of conditioning and priming agents for dentin bonding. PMID- 7988760 TI - Dynamic fatigue of feldspathic porcelain. AB - Several studies (Sherrill and O'Brien, 1974; Southan and Jorgensen, 1974; Jones, 1983) have shown that stress corrosion fatigue occurs in dental porcelains. Morena et al. (1986) reported on an assessment of slow crack growth parameters for dental ceramics. The purpose of the study reported here was to evaluate the fatigue parameters of a model experimental porcelain using dynamic fatigue testing. This test procedure makes use of several constant stressing rates to perform strength tests. Dynamic stress testing was first described by Evans (1974) and later defined as a distinct test modality by Ritter (1978). From such data, the fatigue parameters can be calculated. These fatigue parameters, n and sigma f0, are, respectively, the crack growth exponent from the crack velocity expression and a materials constant which is dependent on the test environment and the inert (moisture-free) strength. The model porcelain was made from 60% component 1 and 40% component 3 according to the Weinstein patent (Weinstein, et al., 1962). The biaxial flexure strength of 300 specimens 1 mm thick was tested in 37 degrees C water by testing 50 samples at each of 6 constant stressing rates: 100, 10, 1, 0.1, 0.01, and 0.001 MPa/s. One hundred specimens were tested in a moisture-free environment at 100 MPa/s using a servo-mechanical testing machine. A commercial porcelain (Jelenko Gingival-Lot # 2012, Jelenko Dental Health Products, Armonk, NY, USA) was chosen as a reference material. One hundred twenty specimens were tested using the same procedures as those used for the model porcelain; however, only 20 samples were tested for 5 stressing rate groups and an inert group.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7988761 TI - Strength of a dental glass-ceramic after surface coating. AB - Clinical evidence suggests that using a resin luting agent rather than a traditional cement reduces the fracture incidence of glass-ceramic crowns. There is some evidence from stress analysis and fractography to indicate that fracture failure is typically initiated from their internal surface. The objective of this study was to determine if surface treatments and cement coatings of the fracture initiating surface affected fracture stresses of ceramic discs in vitro. Glass ceramic discs were cast, crystallized, and given various treatments. The discs were fractured with a ball-on-ring of balls biaxial fixture in air. The maximum stresses at the ceramic-coating interface were calculated using the bi-layer material equations. ANOVA and Tukey's multiple range test revealed that resin coating the fracture-initiating surface increased the biaxial fracture strength of the glass-ceramic discs by 33%. The effect was not reduced by short-term water storage. Etching alone did not significantly alter strength. The results suggest that crack-bridging is the most likely mechanism for the strengthening. Selecting techniques and materials that are likely to enhance crack-bridging may be a practical method of improving the performance of ceramic dental restorations. PMID- 7988762 TI - Auger electron spectroscopy of dentin: elemental quantification and the effects of electron and ion bombardment. AB - Auger electron spectroscopy was used in this investigation to quantify the elemental composition of various dentin surfaces. The surfaces included the "smeared layer," produced by abrasion, as well as surfaces prepared by fracturing in vacuum and in air. Quantification was aided by spectra obtained from standard samples of the two main components of dentin, hydroxyapatite, and collagen. Experimental conditions were found whereby the samples could be analyzed without conductive coatings. Ion sputter etch rates were measured for dentin, hydroxyapatite, and collagen. Under the conditions used here, it was observed that collagen etched at a rate approximately five times greater than hydroxyapatite. Auger spectra of the sputtered surfaces indicated significant ion beam-induced sample changes in collagen and dentin; no significant changes were found with hydroxyapatite. The results of this investigation demonstrate that Auger electron spectroscopy can be used to characterize dentinal surfaces and that ion sputtering can cause changes in the surface composition of dentin. PMID- 7988763 TI - Environmental effect on bond strength of plasma-sprayed hydroxyapatite/bioactive glass composite coatings. Technical note. AB - Bond strength of hydroxyapatite (HA) coatings is one of the major concerns of biomaterials scientists and engineers. This study was conducted to determine the effects of environment (particularly humidity and storage time) on bond strength of HA, bioactive glass (BG) and HA/BG (1:1 by weight) composite coatings on Ti6A14V substrates. Results indicated that the HA coating on Ti6A14V lost bond strength when exposed to either a high ( > 95%) or low ( < 30%) humidity environment. In the high humidity environment, degradation of the coating was quite drastic (nearly 40%). The BG coating was more stable in the low humidity environment but lost much bond strength in the high humidity environment (nearly 40%). The HA/BG composite coating behaved well in both environments. After 30 d, the HA/BG composite coating retained nearly all of its as-coated bond strength. These results imply that tremendous care should be taken in storing and/or shipping HA- or BG-coated Ti6A14V implants or other components. PMID- 7988764 TI - Antibacterial effectiveness of dentin bonding systems. AB - This study examined the antibacterial activities of several commercially available glass ionomer cements, dentin bonding systems and luting agents by employing both agar plate diffusion (APD) and growth inhibition (GI) methods. Amalgam and resin composites were also tested as control materials. In both methods (APD and GI), cylindrical specimens were used. Four bacteria strains were tested: Streptococcus mutans, S. salivarius, S. mitis and S. sanguis. These studies were performed using standardized innoculums with selective media, and the assayed materials were directly applied on the assay cultures and plates. The results of agar plate assay were in accordance with the results of growth inhibition method. The glass ionomer cements showed marked antibacterial activity. On the contrary, amalgam, composites, luting agents and dentinal bonding systems did not affect bacterial growth. The sensitivity of the growth method showed that all the strains were inhibited in the same way by each inhibitory material. The data suggest that the use of glass ionomer cements as cavity liners/bases may reduce the consequences of microleakage due to its antibacterial properties. PMID- 7988765 TI - Pulpal response to a new light-activated fluoride releasing liner. AB - The purpose of this study was to investigate the degree of pulp irritation of a newly developed light-activated fluoride-releasing adhesive resin liner using canine teeth compared to the amount caused by a negative control, zinc oxide eugenol cement (ZOE), and a positive control, silicate cement (silicate). In the cases of unexposed pulp, this experimental liner showed none, slight or moderate pulpal changes at 3 d postoperatively. At 30 and 90 d, no pulpal response to the experimental liner was detected in almost all cases. These findings were similar to the ZOE and better than the silicate. There was less evidence of pulpal irritation produced by the experimental liner. This material seems to be safe to the pulp under the conditions of this study. PMID- 7988767 TI - Impact strength of acrylic resin denture base materials with surface defects. AB - The first part of this study involved the development of a method for evaluating the effect of small surface defects (3.0 microns-80.0 microns) on the impact strength of acrylic denture base materials. The method was used to compare the properties of 12 denture base materials, some of which are described as "high impact strength" products. The defects were introduced by drawing the specimens over abrasive papers of varying grit sizes or by notching with a craft knife. Flexural toughness tests were also carried out in order to evaluate the materials under both rapid (impact) and slow (flexural) rate test conditions. The impact resistance of acrylic resins was significantly reduced by the presence of very small surface defects (e.g., < 16 microns), and this was particularly noticeable for so-called high-impact resins. The latter have values of impact strength only slightly higher than standard acrylic products when defects are present. Testing "notched" specimens with small surface defects was a simple method of obtaining reproducible results. This test was sensitive enough to differentiate among several types of currently available denture base resins. PMID- 7988766 TI - Fluoride release in vitro from various glass ionomer cements and resin composites after exposure to NaF solutions. AB - The release of fluoride from 1) discs made from five glass ionomer cements and two composites, and 2) the same discs after exposure to different NaF solutions, were studied. The specimens were placed in distilled water for 10 wk. After 24 h and then once a week, the specimens were transferred to fresh distilled water. After 5 wk, the specimens were divided into four groups and exposed to 0, 0.02, 0.2 and 2% NaF solutions for 5 min. The fluoride release was highest during the first week after preparation, after which it decreased sharply and then more slowly. The amount of fluoride released was ordered: liner/base > restorative glass ionomer > composites. The composites released significantly less fluoride than the glass ionomer cements. After exposure to NaF, the fluoride release was significantly higher for the silver cermet material than for the other glass ionomers tested. From a clinical point of view, the results from this study imply that glass ionomer restorations may act as intraoral devices for the controlled slow release of fluoride at sites at risk for recurrent caries. PMID- 7988768 TI - Rheological studies of photopolymerized dental composites. AB - An oscillating rheometer was constructed to study the polymerization of light cured dental composites. The instrument is based on the forced harmonic oscillator, where the polymerization of the sample leads to a reduction of amplitude of oscillations. The polymerization time as determined for different materials seemed to be influenced by the filler particle size. The results obtained for the viscosity and shear modulus for a class of samples agreed with values published using other instruments and methods. PMID- 7988769 TI - An in vitro study of two adhesive systems: third and fourth generations. AB - The aim of this in vitro study was to compare the adhesive properties of a manufacturer's third and fourth generation dentin adhesive. Vestibular sections of recently extracted third molars were embedded in chemical-cured acrylic resin and ground with 600-grit silicon carbide sandpaper. Fifteen samples were prepared with the adhesive products and the dentin surfaces were analysed by SEM. Twenty four samples were divided into two groups and prepared with third and fourth generation systems, respectively. Composite filled tubes were then positioned on the prepared dentin surfaces and photopolymerized. The treated samples were kept in distilled water at 37 degrees C for 24 h. Four samples were used to analyze the resin-dentin surface. A tension test was performed on the remaining twenty samples at a crosshead speed of 0.5 mm/min. The results were analyzed using the Fisher and Student t-tests. The fractured surfaces were examined by SEM. The resistance to tensile forces of specimens prepared with the fourth generation system was significantly higher than that obtained after using the third generation system. Thus, as expected from the in vitro tests, the fourth generation system provided better adhesion to dentin than the third generation material. PMID- 7988770 TI - Shear bond of resin cement to post-cured hybrid composites. AB - Various surface treatments affected the shear bond strength of a dual-cured resin cement to a post-cured composite. Disks of post-cured composite inlay 2.0 mm thick by 10.0 mm in diameter, were mounted in acrylic cylinders. Various surface treatments were tested including: 1) smooth material; 2) treated by sandblasting (air abrasion); 3) sandblasting and etching with hydrofluoric acid (HF); 4) sandblasting and silane priming; 5) sandblasting, HF etching and silane priming; 6) HF etching alone; 7) HF etching and silane priming; and 8) silane priming alone. Specimens of dual-cured cement, 4.0 mm in diameter, were light-cured onto the prepared surfaces. The samples were stored in water at 37 degrees C for 7d before shear bond testing. The highest mean shear bond strengths were achieved for specimens with the following surface treatments: 1) by a combination of sandblasting, HF etching and silane priming; 2) sandblasting and HF etching; and 3) sandblasting and silane priming. Most bond failures in these groups were cohesive within the post-cured composite inlay disks. The bond strengths of the specimen in other groups were significantly lower and bond failures were mainly adhesive at the interface between the disk of post-cured composite and dual-cured resin cement. PMID- 7988772 TI - EASD Study Group Artificial Insulin Delivery Systems Pancreas and Islet Transplantation (AIDSPIT). Report of the 13th Workshop of the EASD Study Group AIDSPIT. PMID- 7988771 TI - Acid-base properties of adhesive dental polymers. AB - The surface energetics of three resins (polymethylmethacrylate, polyhydroxyethylmethacrylate, and Bis-GMA/triethyleneglycoldimethacrylate) commonly used in adhesive interactions with tooth hard tissues were evaluated according to the Fowkes acid-base theory of interfacial interactions. From the measurement of the contact angle of test acidic and basic liquids on the sample surfaces, the acid-base contribution to the work of adhesion was evaluated. Results show that polyhydroxyethylmethacrylate is a comparatively strong Lewis base, a finding that can explain the important role played by this material in the formulation of dentin adhesive. PMID- 7988773 TI - DNA fragmentation is an early event in cytokine-induced islet beta-cell destruction. AB - The cytokines, interleukin 1, tumour necrosis factor, and interferon gamma are cytotoxic to islet beta cells, however, their mechanisms of beta-cell killing are not fully characterized. Since DNA damage is a mechanism of cytokine-induced cell death in some cell types, we sought evidence for cytotoxic effects of cytokines at a nuclear level in islet beta cells by measuring DNA fragmentation in rat islets and islet beta-cell lines. The individual cytokines, interleukin 1 (10 U/ml), tumour recrosis factor (10(3) U/ml) and interferon gamma (10(3) U/ml) inhibited insulin release from rat islets, but did not cause DNA fragmentation or destroy islet cells; by contrast, combination of the three cytokines induced DNA fragmentation and islet-cell death. Cytokine-induced DNA fragmentation preceded cell lysis in islet beta-cell lines (RINm5F, rat insulinoma cells; and NIT-1, NOD/Lt mouse transgenic beta cells), whereas in non-islet cell lines (GH-3, rat pituitary; and PC-12, rat adrenal) the cytokines induced cell lysis and no or late DNA fragmentation. Nicotinamide prevented both DNA fragmentation and destruction of RINm5F islet cells by the cytokines. These findings identify DNA as an early target of cytokine action in islet beta cells, and implicate DNA fragmentation as a mechanism of cytokine-induced beta-cell destruction. PMID- 7988774 TI - Development of hyperglycaemia and insulin resistance in conscious genetically diabetic (C57BL/KsJ-db/db) mice. AB - A bolus injection of insulin dose-dependently reduced plasma glucose levels in genetically diabetic (db/db) mice and their normoglycaemic litter-mates (+/+ mice) aged 5, 8 and 12 weeks. Compared between the groups, the dose-response curves showed that insulin resistance was already present in the 5-week-old db/db mice when they were still normoglycaemic. The minimum effective dose of insulin was lower in the +/+ (32 micrograms/kg) than in the db/db (100 micrograms/kg) mice and the maximum response which was obtained at 320-1000 micrograms/kg of the hormone was higher in the former (about 80%) than in the latter (about 55%). Although the basal plasma glucose levels in the db/db mice were significantly increased with age as compared with those in the +/+ mice, the insulin response curves were identical in the db/db mice from 5 to 12 weeks of age. The number of insulin binding sites were significantly decreased by 22-50% (5-12-week-old) in the liver plasma membrane from the db/db mice compared with that from the +/+ mice, while its affinity was not significantly changed between the groups. Streptozotocin (100 mg/kg, i.p.) treatment increased the number of insulin receptors in the db/db mice to a number comparable with those in the +/+ mice. Coinciding with the change, the hypoglycaemic action of insulin was slightly enhanced in the streptozotocin-treated db/db mice compared with that in non treated db/db mice, but was still considerably depressed when compared with that in +/+ mice.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7988775 TI - IDDM susceptibility associated with polymorphisms in the insulin gene region. A study of blacks, Caucasians and orientals. AB - Previous studies have suggested an association between polymorphisms in the insulin gene region and insulin-dependent diabetes mellitus (IDDM). Most of the studies so far have been performed in Caucasoid populations. We have investigated 418 random IDDM patients and 422 healthy control subjects from three different ethnic groups; Tanzanian blacks, Norwegian Caucasians and Japanese orientals. Our data suggest that polymorphisms in the insulin gene region confer susceptibility to IDDM in Caucasians, and that a similar tendency though not statistically significant is observed among Tanzanian blacks, while no significant contribution is seen among Japanese orientals. We further demonstrate that the disease associated genotype INS +/+ confers susceptibility independently of HLA class II alleles associated with IDDM. Compared to the contribution of particular HLA-DQ alleles in IDDM susceptibility, the additional risk conferred by the insulin gene region polymorphism is, however, small. Genotyping of the insulin gene region will therefore most probably not be a useful tool in the prediction of IDDM. PMID- 7988776 TI - The effects of 7-hour local hyperglycaemia on forearm macro and microcirculatory blood flow and vascular reactivity in healthy man. AB - Animal studies suggest that hyperglycaemia directly affects local blood flow and vascular reactivity. We studied the effects of 7 h of local forearm hyperglycaemia, on forearm (muscle) and skin microcirculatory blood flow in 12 healthy men. Furthermore, the effects of this local hyperglycaemia on forearm vasoreactivity to noradrenaline were studied. Using the perfused forearm technique, a local hyperglycaemia of approximately 16 mmol/l was induced by continuous intraarterial infusion of 5% glucose. All subjects received both glucose and placebo (0.9% NaCl) infusions on two different occasions, in random order and blinded for the subjects. Forearm (muscle) blood flow and vascular reactivity to noradrenaline were measured using venous occlusion plethysmography. Skin microcirculatory blood flow was evaluated using intravital capillary microscopy (nutritive blood flow) and laser-Doppler fluxmetry (thermoregulatory blood flow). Measurements were performed at baseline, after 4 h, and after 7 h of intraarterial glucose or placebo infusion. During local glucose infusion there was a slight increase in the levels of insulin, C-peptide, systemic glucose, and blood pressure, compared to the placebo experiments. No differences were observed in forearm blood flow and laser-Doppler flux ratio (infused: contralateral arm), as well as in capillary blood cell velocity between glucose and placebo experiments. Noradrenaline produced similar reductions in forearm blood flow ratio during glucose and placebo experiments. We conclude that in contrast to animal studies, local hyperglycaemia (approximately 16 mmol/l) for 7 h does not affect forearm macro and microcirculatory blood flow or vascular reactivity to noradrenaline in man. PMID- 7988777 TI - Are gender differences in cardiovascular disease risk factors explained by the level of visceral adipose tissue? AB - It has been suggested that the lower prevalence of cardiovascular disease in women before menopause in comparison with men may be explained by differences in body fat distribution, plasma lipoprotein levels and indices of plasma glucose insulin homeostasis. Thus, gender differences in visceral adipose tissue accumulation measured by computed tomography and metabolic variables were studied in 80 men and 69 pre-menopausal women, aged 23-50 years. Despite the fact that women had higher levels of total body fat (p < 0.0001), they displayed lower areas of abdominal visceral adipose tissue (p < 0.06) and a lower ratio of abdominal visceral to mid-thigh adipose tissue areas than men (p < 0.0001). After adjustment for body fat mass, women generally displayed a more favourable risk profile than men which included higher plasma HDL2-cholesterol and lower plasma insulin, apolipoprotein B and triglyceride levels (p < 0.01). Metabolic variables adjusted for body fat mass were then compared between genders after control for differences in abdominal visceral adipose tissue area. After such controls, variables related to plasma glucose-insulin homeostasis were no longer significantly different between men and women. Gender differences for plasma concentrations of triglyceride, apolipoprotein B and the ratio of HDL2 cholesterol/HDL3-cholesterol also disappeared, whereas plasma concentrations of HDL-cholesterol, HDL2-cholesterol as well as the ratio of HDL-cholesterol/total cholesterol remained significantly higher in women than in men (p < 0.01). These results suggest that abdominal visceral adipose tissue is an important correlate of gender differences in cardiovascular disease risk. However, additional factors are likely to be involved in gender differences in plasma HDL-cholesterol levels. PMID- 7988778 TI - Relationship of glucose intolerance to coronary risk in Afro-Caribbeans compared with Europeans. AB - Afro-Caribbeans have low mortality rates from coronary heart disease, despite a high prevalence of diabetes mellitus. We examined 1166 Afro-Caribbean and European men and women aged 40-64 years in a community survey in London, UK. Prevalence of glucose intolerance (combining impaired glucose tolerance, new and known diabetes) was 31% in Afro-Caribbeans and 14% in Europeans (p < 0.001). In men, the prevalence of probable coronary heart disease was 6% in Afro-Caribbeans and 13% in Europeans (p < 0.01). Triglyceride was lower in Afro-Caribbeans than Europeans; in men, HDL cholesterol was higher. Afro-Caribbean men were less centrally obese, while Afro-Caribbean women were more centrally obese than their European counterparts. Fasting and 2-h insulin levels were higher in Afro Caribbeans than Europeans. Glucose intolerance was associated with high triglyceride, low HDL cholesterol and central obesity in European but not in Afro Caribbean men. In Europeans, fasting triglyceride was 1.49 mmol/l in normoglycaemic and 1.89 mmol/l in glucose intolerant men (p < 0.05), in Afro Caribbean men triglyceride was 1.08 and 1.22 mmol/l, respectively. Waist hip ratio was 0.94 in normoglycaemic, and 0.98 in glucose intolerant European men (p < 0.001). In Afro-Caribbean men, waist hip ratio was 0.93 in both groups. At each level of insulin, glucose or central obesity, triglyceride was lower in Afro Caribbean men and women than in Europeans. We speculate that despite high insulin levels, Afro-Caribbeans have a favourable lipoprotein pattern which persists in the presence of glucose intolerance, and may be related to body fat distribution.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7988779 TI - Serum cholesterol and cholesterol and lipoprotein metabolism in hypercholesterolaemic NIDDM patients before and during sitostanol ester-margarine treatment. AB - Cholesterol absorption and metabolism and LDL and HDL kinetics were investigated in 11 hypercholesterolaemic non-insulin-dependent diabetic men off and on a hypolipidaemic treatment with sitostanol ester, (3 g sitostanol daily) dissolved in rapeseed oil margarine, by a double-blind crossover study design. Serum total, VLDL and LDL cholesterol and apoprotein B fell significantly by 6 +/- 2, 12 +/- 6, 9 +/- 3 and 6 +/- 2%, mean +/- SEM, and HDL cholesterol was increased by 11 +/ 4% (p < 0.05) by sitostanol ester. LDL cholesterol and apoprotein B were significantly decreased in the dense (1.037-1.055 g/ml), but not light, LDL subfraction due to a significantly diminished transport rate for LDL apoprotein B, while the fractional catabolic rate was unchanged. HDL kinetics, measured with autologous apoprotein A I, was unaffected by sitostanol ester. Cholesterol absorption efficiency was markedly reduced from 25 +/- 2 to 9 +/- 2% (p < 0.001) during sitostanol ester followed by proportionately decreased serum plant sterol proportions. Cholesterol precursor sterol proportions in serum, fecal neutral sterol excretion, and cholesterol synthesis, cholesterol transport, and biliary secretion were all significantly increased by sitostanol ester. We conclude that the sitostanol ester-induced decrease in cholesterol absorption compensatorily stimulated cholesterol synthesis, had no effect on fractional catabolic rate, but decreased transport rate for LDL apoprotein B so that serum total, VLDL and LDL cholesterol levels were decreased.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7988780 TI - Effect of glipizide treatment on postprandial lipaemia in patients with NIDDM. AB - The primary goal of the present study was to examine the effects of improved glycaemic control associated with glipizide treatment on postprandial lipaemia in non-insulin-dependent diabetic patients. The metabolism of triglyceride-rich lipoproteins of intestinal origin was assessed by measuring the retinyl palmitate content in plasma and the Svedberg flotation index (Sf) > 400 and Sf 20-400 lipoprotein fractions. Fasting plasma glucose concentrations (14.5 +/- 0.5 vs 9.0 +/- 0.5 mmol/l), glycated haemoglobin levels (13.1 +/- 0.6 vs. 9.7 +/- 0.6%), and daylong plasma glucose concentrations were all significantly lower after glipizide treatment (p < 0.001). The improvement in glycaemic control was associated with increases in insulin-mediated glucose uptake (p < 0.001) and plasma post-heparin lipoprotein and hepatic lipolytic activities (p < 0.02). Both fasting plasma triglyceride (3.09 +/- 0.51 vs 2.37 +/- 0.34 mmol/l), and postprandial triglyceride concentrations (p < 0.05-0.001) were lower following glipizide treatment, associated with a significant fall in retinyl palmitate content in all three lipoprotein fractions (p < 0.02-0.001), with the most substantial decrease seen in the Sf20-400 fraction. These data indicate that glipizide-induced improvement in glycaemic control was associated with changes in the metabolism of triglyceride-rich lipoproteins of intestinal origin that would be anticipated to reduce risk of coronary heart disease in non-insulin-dependent diabetic patients. PMID- 7988781 TI - Early recognition of autonomic dysfunction in microalbuminuria: significance for cardiovascular mortality in diabetes mellitus? AB - The appearance of microalbuminuria in diabetic patients predicts development of macroalbuminuria and coronary heart disease. Autonomic dysfunction in ischaemic heart disease is related to an increased incidence of arrhythmic deaths. To assess sympathovagal balance in relation to microalbuminuria we performed 24-h spectral analysis of RR interval oscillations in 37 insulin-dependent diabetic patients. Patients were divided according to urinary albumin excretion as normo (< 20 micrograms/min) (n = 12), micro-(> 20 and < 200 micrograms/min) (n = 14) and macro-albuminuria (> 200 micrograms/min) (n = 11). None had symptoms or signs of ischaemic heart disease at clinical examination or during stress testing. Fourteen matched healthy subjects served as controls. Overall RR interval variability was calculated as the 24-h standard deviation. The square root of power of the low-frequency (0.04-0.15 Hz) and high-frequency (0.15-0.40 Hz) component were considered indices of the sympathovagal interaction and vagal function, respectively. Patients with micro and macroalbuminuria had, compared to control subjects, significantly reduced 24-h standard deviation, a much smaller day/night difference in mean RR level and a significantly reduced amplitude of the low frequency and high frequency oscillations, which were even more reduced in macroalbuminuria. The differences in vagal function were also present after correction for mean RR level, and differences in physical training level and smoking. Insulin-dependent diabetic patients who develop microalbuminuria have significantly impaired vagal function and abnormal sympathovagal interaction, which is further deranged in macroalbuminuria. This early autonomic dysfunction may later contribute to a increased risk for sudden cardiac death. PMID- 7988783 TI - Association of particular HLA class II alleles, haplotypes and genotypes with susceptibility to IDDM in the Belgian population. AB - Using a highly discriminatory DNA typing technique, based on the polymerase chain reaction and reverse dot blot hybridization, more refined results were obtained on the association of particular HLA class II alleles, haplotypes and genotypes with insulin-dependent diabetes mellitus in the Belgian population. The previously reported predisposing effect for the DRB1*0301 encoded DR3 serologic specificity was confirmed and could be assigned to the DRB3*0200 encoded DR52b serologic specificity. A second high risk haplotype, DRB1*0401-DQB1*0302 encoding the DR4-DQ8 serologic specificity, accounted for increased susceptibility both in the total insulin-dependent diabetic population and among DR4-positive patients. Moreover, we found that these DR4 associated DRB1 and DQB1 alleles act as independent risk factors. A possible role for the DPB1 locus can be rejected since the observed predisposing effect for DPB1*0202 probably occurred due to linkage disequilibrium of this allele with DRB1*0301. Particular extended haplotypes accounted for the decreased relative risk observed for the DR2, DR11 and DR13 serologic specificities. The highest relative risk was observed for those DQA1/DQB1 genotypes, allowing for the formation of 4SS (DQ alpha Arg52+/DQ beta Asp57-) heterodimers. PMID- 7988782 TI - Relative roles of insulin and hypoglycaemia on induction of neuroendocrine responses to, symptoms of, and deterioration of cognitive function in hypoglycaemia in male and female humans. AB - To assess the relative roles of insulin and hypoglycaemia on induction of neuroendocrine responses, symptoms and deterioration of cognitive function (12 cognitive tests) during progressive decreases in plasma glucose, and to quantitate glycaemic thresholds, 22 normal, non-diabetic subjects (11 males, 11 females) were studied on four occasions: prolonged fast (n = 8, saline euglycaemia study, SA-EU), stepped hypoglycaemia (plasma glucose plateaus of 4.3, 3.7, 3 and 2.3 mmol/l) or euglycaemia during insulin infusion at 1 and 2 mU.kg 1.min-1 (n = 22, high-insulin hypoglycaemia and euglycaemia studies, HI-INS-HYPO and HI-INS-EU, respectively), and stepped hypoglycaemia during infusion of insulin at 0.35 mU.kg-1.min-1 (n = 9, low-insulin hypoglycaemia study, LO-INS HYPO). Insulin per se (SA-EU vs HI-INS-EU), suppressed plasma glucagon (approximately 20%) and pancreatic polypeptide (approximately 30%), whereas it increased plasma noradrenaline (approximately 10%, p < 0.05). Hypoglycaemia per se (HI-INS-HYPO vs HI-INS-EU) induced responses of counterregulatory hormones (CR HORM), symptoms and deteriorated cognitive function. With the exception of suppression of endogenous insulin secretion, which had the lowest glycaemic threshold of 4.44 +/- 0.06 mmol/l, pancreatic polypeptide, glucagon, growth hormone, adrenaline and cortisol had similar glycaemic thresholds (approximately 3.8-3.6 mmol/l); noradrenaline (3.1 +/- 0.0 mmol/l), autonomic (3.05 +/- 0.06 mmol/l) and neuroglycopenic (3.05 +/- 0.05 mmol/l) symptoms had higher thresholds. All 12 tests of cognitive function deteriorated at a glycaemic threshold of 2.45 +/- 0.06 mmol/l, but 7 out of 12 tests were already abnormal at a glycaemic threshold of 2.89 +/- 0.06 mmol/l. Although all CR-HORM had a similar glycaemic threshold, the lag time of response (the time required for a given parameter to increase) of glucagon (15 +/- 1 min) and growth hormone (14 +/- 3 min) was shorter than adrenaline (19 +/- 3 min) and cortisol (39 +/- 4 min) (p < 0.05). With the exception of glucagon (which was suppressed) and noradrenaline (which was stimulated), insulin per se (HI-INS-HYPO vs LO-INS-HYPO) did not affect the responses of CR-HORM, and did not influence the symptoms or the cognitive function during hypoglycaemia. Despite lower responses of glucagon, adrenaline and growth hormone (but not thresholds) in females than males, females were less insulin sensitive than males during stepped hypoglycaemia. PMID- 7988785 TI - Effect of metformin on insulin-stimulated glucose transport in isolated skeletal muscle obtained from patients with NIDDM. AB - Metformin has been demonstrated to lower blood glucose in vivo by a mechanism which increases peripheral glucose uptake. Furthermore, the therapeutic concentration of metformin has been estimated to be in the order of 0.01 mmol/l. We investigated the effect of metformin on insulin-stimulated 3-0-methylglucose transport in isolated skeletal muscle obtained from seven patients with non insulin-dependent diabetes mellitus (NIDDM) and from eight healthy subjects. Whole body insulin-mediated glucose utilization was decreased by 45% (p < 0.05) in the diabetic subjects when studied at 8 mmol/l glucose, compared to the healthy subjects studied at 5 mmol/l glucose. Metformin, at concentrations of 0.1 and 0.01 mmol/l, had no effect on basal or insulin-stimulated (100 microU/ml) glucose transport in muscle strips from either of the groups. However, the two control subjects and three patients with NIDDM which displayed a low rate of insulin-mediated glucose utilization (< 20 mumol.kg-1.min-1), as well as in vitro insulin resistance, demonstrated increased insulin-stimulated glucose transport in the presence of metformin at 0.1 mmol/l (p < 0.05). In conclusion, the concentration of metformin resulting in a potentiating effect on insulin stimulated glucose transport in insulin-resistant human skeletal muscle is 10 fold higher than the therapeutic concentrations administered to patients with NIDDM. Thus, it is conceivable that the hypoglycaemic effect of metformin in vivo may be due to an accumulation of the drug in the extracellular space of skeletal muscle, or to an effect of the drug distal to the glucose transport step. PMID- 7988784 TI - Pancreatic beta-cell secretory defect associated with mitochondrial point mutation of the tRNA(LEU(UUR)) gene: a study in seven families with mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes (MELAS). AB - Recent evidence suggests possible linkage between diabetes mellitus and mitochondrial gene mutation. We surveyed mitochondrial tRNA(LEU(UUR)) (3243) mutation in 7 mitochondrial encephalomyopathy, lactic acidosis and stroke-like episode (MELAS) families and identified 24 mutated subjects (7 MELAS probands and 17 non-MELAS relatives) as well as 11 non-mutant family members. An OGTT in the 24 mutant relatives revealed 14 diabetic subjects, 3 with impaired glucose tolerance and 7 with normal glucose tolerance and all non-mutant family members as having normal glucose tolerance. Insulinogenic index was significantly reduced in the mutant diabetic subjects and those with impaired and normal glucose tolerance in comparison with the normal control subjects and the non-mutant members. Urinary 24-h C-peptide immunoreactivity excretion was markedly reduced in the mutant diabetic subjects and those with normal and impaired glucose tolerance, compared with the control subjects and the non-mutant family members. Plasma C-peptide immunoreactivity 6 min after glucagon injection was markedly reduced in the mutant diabetic subjects and those with normal and impaired glucose tolerance compared with the control subjects and the non-mutant family members. Si, an index of insulin sensitivity of the four mutant subjects was within normal range. Islet cell antibodies were negative in sera of eight mutated diabetic subjects, 2 and 6 with impaired and normal glucose tolerance, respectively. Diabetic retinopathy and nephropathy were demonstrated in 7 (50%) and 12 (85.7%) of 14 mutant diabetic subjects, respectively.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7988787 TI - Translocation of protein kinase C alpha and zeta in rat glomerular mesangial cells cultured under high glucose conditions. AB - The activities and expression of protein kinase C isoenzymes were examined in glomerular mesangial cells cultured under high glucose conditions. Exposure of cells to high glucose concentrations (27.8 mmol/l) for more than 3 days resulted in a significant elevation of protein kinase C activities in the membrane fraction. Of the protein kinase C isoenzymes, the levels of protein kinase C alpha significantly increased in the membrane fraction after 3 days of exposure to glucose, and protein kinase C zeta increased after 5 days of exposure. Levels of protein kinase C delta and epsilon remained unchanged and protein kinase, C beta and gamma were not detected. These results indicate that protein kinase C alpha and zeta are translocated under high glucose conditions possibly through different mechanisms. PMID- 7988786 TI - Analysis of cytokine mRNA expression in syngeneic islet grafts of NOD mice: interleukin 2 and interferon gamma mRNA expression correlate with graft rejection and interleukin 10 with graft survival. AB - The injection of complete Freund's adjuvant into diabetic nonobese diabetic (NOD) mice at the time of syngeneic islet transplantation prevents monocytic/lymphocytic cell infiltration into the islet graft, Beta-cell destruction, and autoimmune diabetes recurrence. We have used semiquantitative reverse transcriptase-polymerase chain reaction analysis to examine and compare cytokine mRNA expression profiles in islet grafts from complete Freund's adjuvant injected and control NOD mice. Interleukin 10 mRNA expression was significantly increased whereas interleukin 2 and interferon gamma mRNA levels were significantly decreased in islet grafts from complete Freund's adjuvant-injected mice compared to control mice. Levels of mRNA for interleukin 1 beta, interleukin 4, and tumour necrosis factor alpha were not significantly different in islet grafts from complete Freund's adjuvant-injected and control mice. These findings suggest that a Th1 subset of lymphocytes and their cytokine products, interleukin 2 and interferon gamma, may be involved in the rejection of syngeneic islet grafts and diabetes recurrence in NOD mice, and that the protective effect of complete Freund's adjuvant may result from the induction of interleukin 10 production and consequent down-regulation of Th1 cells and cytokines in the islet graft. PMID- 7988788 TI - Non-isotopic and sensitive method for diagnosis of maternally-inherited diabetes and deafness. PMID- 7988789 TI - Evaluation of octreotide to assess insulin-mediated glucose disposal by the insulin suppression test. PMID- 7988790 TI - Selection of control subjects for case/control analysis of susceptibility to type 1 (insulin-dependent) diabetes mellitus. PMID- 7988791 TI - Analysis of a novel cyclic Amp inducible prespore gene in Dictyostelium discoideum: evidence for different patterns of cAMP regulation. AB - The D7 cDNA clone hybridizes to a 2.8 kb mRNA which first appears at the mound stage of development in the cellular slime mold Dictyostelium discoideum. This gene which is cyclic AMP (cAMP) inducible and is expressed specifically in the prespore cells contains an open reading frame interrupted by only one intron. The predicted amino acid sequence indicates a novel prespore protein which differs from all of the previously described prespore proteins in that it contains no internal repeats and does not share any homology with any of the other prespore genes. The amino acid sequence predicts a protein of 850 amino acids with a molecular weight of 95,343 daltons and an isoelectric point of 4.25. The protein is very rich in glutamine (13.8%), asparagine (10.6%) and glutamic acid (10.4%) with one potential glycosylation site and 28 possible sites for phosphorylation. The amino terminus is hydrophobic with characteristics of a signal sequence while the entire carboxyl half of the protein is notable for its hydrophilicity. Comparison of cAMP regulation of the D7 gene with the regulation of two other cAMP regulated prespore genes, the PL3(SP87) gene and the Psa(D19), reveals some striking differences. Disaggregation in the presence of cAMP results in transient degradation of mRNA for all three genes. The transcription rate for the D7 and PsA(D19) genes remains relatively unaffected by disaggregation but there is a rapid although transient decline in the transcription rate of the PL3(SP87) gene. Although the accumulation of all three mRNAs is first detectable at mound stage, transcription of the D7 and PsA(D19) genes is detected earlier in development, at rippling aggregate stage several hours prior to the earliest time when transcription of the PL3(SP87) gene is detected. Analysis of the promoter region of the D7 gene reveals three CA like boxes flanked by direct repeats as well as four G rich regions that may serve as regulatory elements. PMID- 7988792 TI - The level of sequestered calcium in vegetative amoebae of Dictyostelium discoideum can predict post-aggregative cell fate. AB - When freshly starved amoebae of Dictyostelium discoideum are stained with chlortetracycline (CTC), a cell type-specific fluorescent probe for membrane associated calcium (CA2+) the resulting fluorescence distribution falls into two functional classes. Fluorescence-activated cell sorting shows that highly fluorescing amoebae tend to enter the prestalk pathway while those with low fluorescence tend to become prespores. In the light of previous findings, these results indicate that in addition to cell cycle phase at starvation, phenotypic variation in the level of sequestered calcium is an early correlate of cell fate. PMID- 7988793 TI - Constitutive expression of a microinjected glucose-regulated protein (grp78) fusion gene during early Xenopus laevis development. AB - In this study we have found that a rat glucose-regulated protein (grp) 78 chloramphenicol acetyltransferase (CAT) fusion gene deleted to -456 bp at the 5' end and injected into fertilized Xenopus eggs was first expressed in a constitutive manner in late blastula stage embryos and displayed increased expression as the embryos developed to the gastrula and neurula stages. Using a series of internal deletion mutants and linker-scanner mutants of the rat grp78 promoter, we have found that a CCAAT box and CCAAT-like element within the region -129 to -90 were essential for constitutive expression of the chimeric genes in neurula stage embryos. These results suggest conservation of the regulatory sequences within the grp78 promoter between rat and Xenopus. Interestingly, deletion or alteration of sequences between -130 and -149 had a dramatic stimulatory effect on basal promoter activity. This effect, which was not observed previously in rat cells, may be the result of upstream elements that are transcriptionally active in Xenopus and that can compensate for the mutated or deleted sequences. It is also possible that these results indicate the presence of a negative regulatory element that is recognized by the Xenopus transcriptional apparatus. PMID- 7988794 TI - Expression of nuclear retinoic acid receptors during mouse odontogenesis. AB - The developmental expression of retinoic acid (RA) nuclear receptors RAR(alpha, beta, gamma) and RXR(alpha, beta, gamma) was analysed during mouse odontogenesis by in situ hybridization on frozen sections and compared with the expression patterns of the cellular retinoic acid binding proteins CRABPI and II. The transcripts distribution of each RAR and RXR was basically similar in developing molars and incisors. RAR alpha and RXR alpha were preferentially expressed in dental epithelia, whereas RAR gamma and RXR gamma were transcribed in the dental mesenchyme. RAR beta, RAR gamma and RXR beta displayed both epithelial and mesenchymal expression. RAR beta expression was initiated during bell stage. RXR gamma transcripts were observed only at day 19.5 post coitum in the mitogenic mesenchyme facing the epithelial loops. Odontoblasts expressed RAR beta and RAR gamma, RXR alpha and RXR beta. Preameloblasts expressed RXR alpha and RXR beta and ameloblasts RXR gamma, RXR alpha and RXR beta. RAR alpha transcription in the incisor preameloblasts and ameloblasts was not observed in the first molar. The coexpression between RARs and RXRs might be important to form RAR/RXR heterodimers which are necessary to activate the transcriptions of target genes. CRABPI and CRABPII demonstrated graded variation of expression during odontogenesis in the mesenchyme and in the inner dental epithelium respectively. The pattern of CRABPI transcripts overlapped at least partially with expressions of all the studied nuclear receptors whereas CRABPII epithelial expression was superimposed with the transcription of RAR alpha, RXR alpha and RXR beta. These cytoplasmic proteins might participate in the storage and/or metabolism of RA and then distribute RA to colocalized nuclear receptors.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7988795 TI - Developmental and hormonal regulation of Wnt gene expression in the mouse mammary gland. AB - Ectopic expression of Wnt-1 in the mammary epithelium causes hyperplasias and increases the frequency of tumour formation. Other members of the Wnt gene family are naturally expressed in the breast and are thought to be involved in controlling mammary gland development. Using Northern and in-situ hybridisation, differential expression of Wnt-2, Wnt-4, Wnt-5a, Wnt-5b, Wnt-6 and Wnt-7b in epithelial and mesenchymal compartments was observed. Complex patterns of Wnt expression were found during the ductal, lobulo-alveolar and involution phases of development. Finally, Wnt-2, Wnt-4 and Wnt-5b were shown to be regulated by ovarian hormones. These results suggest that Wnt genes have non-redundant roles in breast development and may be involved in the hormonal regulation of mammary growth. PMID- 7988796 TI - Surface antigens of cell subpopulations in prenatal rat brain are expressed in a characteristic non-random pattern on their ethylnitrosourea-induced malignant counterparts. AB - Selective induction of neural tumors in the rat by single-dose exposure of the immature nervous system to ethylnitrosourea (EtNU) is a model for the study of cell lineage-, differentiation stage-, and carcinogen-dependent mechanisms in neuro-oncogenesis. Overall yields and relative frequencies of different types of neural tumors vary with the developmental window chosen for the EtNU-pulse. Precursor cells belonging to different neural lineages and targeted by the carcinogen at distinct developmental stages may thus bear a differential risk of malignant conversion. To specify subpopulations of neural precursors in fetal (prenatal day 18) BDIX-rat brain, four monoclonal antibodies (mAbs) recognizing cell surface differentiation antigens were used: mAb RB13-2 directed against O acetylated gangliosides and binding to approximately 36% of fetal brain cells (FBC); mAb RB13-6 recognizing a 130 kDa glycoprotein (expressed by approximately 8% of FBC); and mAbs RB21-7 and RB21-15 which bind, respectively, to embryonal neural cell adhesion molecules (N-CAM) and a 24 kDa protein (expressed by approximately 55% and 12% of FBC). Antigen expression profiles were compared with those of 14 primary brain tumors and 16 malignant neural cell lines, all of which had been induced by EtNU on prenatal day 18 in vivo. Monoclonal antibodies RB13-2 and RB21-7 did not bind to any of the tumors or cell lines. In contrast, mAbs RB13-6 and RB21-15 both reacted with 14/14 tumors, and with 16/16 and 10/16 cell lines, respectively. Expression of the latter antigens might thus specify lineage specific stages of FBC development/differentiation particularly susceptible to EtNU-induced malignant transformation. Two-color fluorescence analyses revealed three subsets of FBC binding mAb RB13-6 (RB13-2+/RB13-6+/RB21-15-; RB13-2-/RB13 6+/RB21-15-; and RB13-2-/RB13-6+/RB21-15+), representing successive stages of differentiation. PMID- 7988797 TI - Five years' time difference is too long. PMID- 7988798 TI - More on childhood clustering. PMID- 7988799 TI - Role models during residency training important. PMID- 7988800 TI - Family medicine: a threat to academic homeostasis. PMID- 7988801 TI - Prescription-writing skills questioned. PMID- 7988802 TI - Mentoring at every moment. PMID- 7988803 TI - Entry of US medical school graduates into family practice residences: 1993-1994 and 3-year summary. AB - This is the 13th report prepared by the American Academy of Family Physicians (AAFP) on the percentage of each US medical school's graduates entering family practice residency programs. Approximately 12.3% of the 15,564 medical school graduates between July 1992 and June 1993 were first-year family practice residents in October 1993, compared with 10.8% the previous year. This is the highest percentage since 1983-1984. Medical school graduates from publicly funded medical schools were more than twice as likely to be first-year family practice residents in October 1993 as were residents from privately funded schools, 15.9% compared with 7.1%. The Mountain region again reported the highest percentage of medical school graduates who were first-year residents in family practice programs in October 1993 at 19.1%; the Middle Atlantic and New England regions continued with the lowest percentages at 7.7% and 6.6%, respectively. At least one in four graduates from nine medical schools during the reporting period was in a family practice residency program in October 1993; only two medical schools had this distinction in 1992. Approximately one in two medical school graduates entering a family practice residency program as first-year residents in October 1993 entered a program in the same state where they graduated from medical school. The percentages for each medical school have varied substantially from year to year since the AAFP began reporting this information. The average percentage for each medical school for the last 3 years is reported.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7988804 TI - Results of the 1994 National Resident Matching Program: family practice. AB - The 1994 National Resident Matching Program results reveal a 14% increase in positions filled in family practice residencies, compared with 1993 (2,293 vs 2,002) and a 13% increase in positions filled by US seniors (1,850 vs 1,636). Similarly, 9% more positions were filled on July 1, 1994, than 1993 (3,040 vs 2,798). For the first time, in 1994 more than 3,000 first-year residency positions were filled in family practice. One hundred more US seniors matched in internal medicine, and 74 more US seniors matched in pediatrics. Given the anticipated career choices of students entering residency training in the generalist disciplines, it is expected that 31% of the class of 1994 (Liaison Committee on Medical Education (LCME)-accredited medical schools) will practice as generalists. An 8% increase in first-year positions offered, and the development of 10% new Accreditation Council for Graduate Medical Education accredited family practice residency programs could accommodate 20% of the nation's graduates of LCME- and American Osteopathic Association-accredited medical schools. With increasing interest in family practice careers, increased support for the nation's family practice residency programs is critical. PMID- 7988805 TI - Markers of successful recruitment of students to family practice residency programs. AB - BACKGROUND AND OBJECTIVES: With limited numbers of medical students choosing a primary care specialty, family practice residency programs have had to complete to fill available residency positions. The purpose of this study was to determine the characteristics of the recruiting process used by US family practice residencies and to compare recruiting strategies used by successful and unsuccessful programs. METHODS: We surveyed program directors of all 361 nonmilitary, accredited, US family practice residency programs in existence for more than 2 years. The questionnaire elicited information on program descriptors, recruitment process, and fill rate in the National Resident Matching Program. RESULTS: Seventy-eight percent (282) of the program directors returned usable questionnaires. Success in filling available positions through the Match was significantly associated with high quality of current housestaff and faculty and current residents' positive feelings about the program (P < .01). Program directors perceived successful programs as having an outstanding reputation and being regarded positively by other departments within the institution (P < .01). Programs in the Pacific and Mountain regions of the United States are more successful in recruitment. Programs not filling available positions through the Match spent more effort in recruiting strategies such as mailing and marketing materials (P < .01). CONCLUSION: Having high-quality faculty, housestaff, and residents with good attitudes are markers of success in the Match. Less successful programs appear to try harder to attract residents. PMID- 7988806 TI - The effects of video advertising on physician recruitment to a family practice residency program. AB - BACKGROUND: The number of medical students entering family practice residencies has been decreasing in recent years. In an effort to increase this number, many family practice residencies send videos describing their programs to prospective applicants. This study was designed to evaluate the effects of video advertising on resident recruitment. METHODS: In the fall of 1992, a short promotional video was produced to highlight many aspects of the University of Maryland Family Practice Residency Program. The video was sent to half of all persons who applied to the program. RESULTS: Of the 248 inquiries, 120 (48%) received the video. Of these, 35 (29%) completed the application compared with 69 (54%) who received routine materials only. Applicants who did not receive the video were 2.86 times more likely (95% confidence interval 1.6-5.0) to apply to our program (P < 0.0001). None of the applicants who received the video matched with the program (P < 0.005). CONCLUSION: Residency recruitment videos may have a negative impact on residency recruitment. PMID- 7988807 TI - Changes in medical students' perceptions of family practice resulting from a required clerkship. AB - BACKGROUND: Career choice research has shown that exposing medical students to family medicine, through a special medical school emphasis or a required clerkship, correlates with an increased rate of selection of family practice. It has been hypothesized that actual exposure to family medicine mitigates the negative stereotypes held by many medical students. METHODS: This study used a qualitative strategy to examine how a family medicine clerkship altered medical students' perceptions and attitudes toward this specialty. A series of 12 focus groups were conducted with the students who had just completed a required family medicine junior core clerkship at our institution. RESULTS: Focus group findings confirmed the existence of negative stereotypes about family practice among medical students and provided additional information on their nature and origins. In addition, student comments indicated that a third-year family medicine clerkship experience dispelled this negative stereotyping and instilled in students a greater respect for and interest in family practice. CONCLUSION: Third year clerkships can enhance students' perceptions of family practice by dispelling negative stereotypes and by providing medical students with a more accurate portrayal of the nature of this primary care specialty. PMID- 7988809 TI - Medical school application essays and specialty choice. AB - OBJECTIVE: To identify factors that could be used to predict physician specialty selection at the level of admissions to medical school. METHODS: Content analysis was performed on 161 personal statements from the American Medical College Admission Service application form. Randomly selected graduates analyzed were from the classes of 1985-1987 from a Midwestern public medical school. RESULTS: Fifty percent of those who stated that they had contact with a medical specialty entered either that specialty or a closely related specialty. Of the 11 applicants who stated a goal of entering family practice, one entered family practice. CONCLUSIONS: Contact with a specialty prior to entering medical school may be a significant predictor of the prospective student's eventual specialty selection. However, goals mentioned in the statements are not predictors of specialty choice. PMID- 7988808 TI - Attitudes toward and subsequent career choice of family practice: a weak relationship. AB - BACKGROUND & OBJECTIVES: This study examined longitudinal relationships between attitudes and career choice in family practice from admission to medical school through the end of internship. METHODS: The sample included medical students graduating in 1990 and 1991. Surveys completed at the beginning of each year of medical school, at graduation, and at the end of PGY1 included measures of attitudes toward family practice and stated career choice at the time of each survey. Regression examined the relationship between attitudes and choice; repeated ANOVA measures examined changes over time. RESULTS: Positive attitude scores toward family practice increased over the first 2 years, then declined; women's scores were higher. The proportion of students stating a preference for family practice also increased initially but declined overall; women chose family practice more frequently. Relationships between attitudes and choice were weak over time and neither attitude scores nor change in scores predicted specialty choice. CONCLUSIONS: Although attitudes toward family practice remained positive throughout the 5-year study, student interest in family practice declined during the clinical years. Women maintained stronger interests in family practice than men; the reasons for this are not clear. Attitudes were poor predictors of choice. Care is needed in interpreting cross-sectional studies reporting significant relationships. We need to develop more sensitive attitude measures to improve the predictive validity of attitude measurement scales. PMID- 7988810 TI - Screening for mental health using adolescent-reported parenting. AB - BACKGROUND AND OBJECTIVES: Little is known in primary care practices about the relationship between parenting and adolescent mental health. In addition, current parenting measures have a narrow focus or do not lend themselves to clinical intervention. This study examined the clinical utility of a new instrument measuring adolescent-reported parenting, the Parenting Assessment Scale (PAS), to predict adolescent mental health. METHODS: A total of 147 adolescents regularly attending an inner-city clinic were asked to complete the Youth Self Report (YSR), a standard scale measuring mental health, and a PAS for each biological parent. Global scores on the PAS and YSR summarized the reported parenting quality and the adolescents' mental health status. RESULTS: Receiver Operating Characteristics and discrimination analyses showed that the global parenting index was highly predictive of mental health using a z score of .73 (sensitivity = 92.3%, specificity = 88.9%). CONCLUSIONS: The PAS may be useful as a screening tool in older, black adolescent females, although further research is needed to clarify its role in the clinical setting. PMID- 7988811 TI - Detecting depression in elderly outpatients: findings from depression symptom scales and the Dartmouth COOP charts. AB - BACKGROUND: The diagnosis and treatment of depression in elderly adults is a serious concern in outpatient settings, where it is well known that practicing physicians often overlook the possibility of depression in adult patients of all ages. Detecting depression in elderly patients can present different problems than detection in younger patients, and special instruments have been developed to screen for depressive symptoms in the elderly. These instruments are not commonly used in family practice settings because of time constraints and confusion about details on how to use them. METHODS: This study compared four commonly accepted depression scales: the Geriatric Depression Scale (GDS), the Beck Depression Inventory Short Form, the Durham GRECC, and the Brief Carroll Scale, and one functional assessment instrument, the Dartmouth COOP Functional Assessment Charts/WONCA, in identifying depressive symptoms in 100 patients 65 years and older (mean 71.6 years) attending an outpatient family practice residency clinic. These results were compared with actual chart records relating to depression and depression symptoms. RESULTS: The prevalence of depressive symptoms in this elderly outpatient population fell within the range of 16.5% 34.7%, according to scores on the various depression scales. Review of the same patients' medical records revealed that only 7% had been given a diagnosis of or were being treated for depression by their physician. The three shorter depression scales correlated well with the longer GDS, indicating that they may be substitutable for the more lengthy GDS. The Dartmouth COOP Functional Assessment Charts/WONCA proved to have a high level of consistency between the findings from its emotional condition component and the results of the depression symptom scales. CONCLUSION: This study affirms the potential utility of depression symptom screening scales in the outpatient setting. It also points to the possible utility of the emotional condition component of the Dartmouth COOP Functional Assessment Charts/WONCA as a screening question to be followed, as appropriate, by more formal instruments or clinical interview for depression in elderly outpatients. PMID- 7988812 TI - Half full or half empty? A look at family practice specialty choice after strolling through the 1994 match. PMID- 7988813 TI - Prophylactic antibiotic treatment in therapeutic or complicated diagnostic ERCP: results of a randomized controlled clinical study. AB - The present study evaluated the effects of prophylactic administration of cefotaxime in patients undergoing therapeutic or complicated diagnostic ERCP. One hundred patients were randomized to two groups of 50 patients each. Patients in group 1 received an intravenous infusion of 2 g cefotaxime 15 minutes before endoscopy; patients in group 2 did not receive an intravenous antibiotic before ERCP (control group). Blood samples were drawn for bacteriologic cultures before endoscopy and 5, 15, 30, and 120 minutes after beginning the procedure. Bacteremia was detected by blood cultures (15- and 30-minute samples) in 4 patients who did not receive prophylactic antibiotics (Escherichia coli in 2 cases, Peptostreptococcus in 1, and Staphylococcus aureus in 1). Cholangitis or sepsis did not occur after the bacteremic episodes in any of these patients. In 4 other patients who did not receive cefotaxime-all of whom had biliary obstruction clinical cholangitis or sepsis developed during the 3-day follow-up; ERCP had failed to decompress the biliary system completely in these 4 cases. Blood cultures identified bacteria in 3 of these 4 patients (Pseudomonas aeruginosa in 1, E. coli in 2). Thus, bacteremia or clinical sepsis developed in 8/50 patients (16%) in the control group without antibiotic prophylaxis, whereas no such episode was observed in patients who had received prophylactic treatment (chi 2 = 8.7; p < 0.01). The present results indicate that prophylactic administration of an antibiotic such as cefotaxime can reduce the incidence of bacteremia and sepsis in patients who undergo therapeutic or complicated diagnostic ERCP.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7988814 TI - Antibiotic prophylaxis in patients with infectious risk factors undergoing gastrointestinal endoscopic procedures. AB - Consecutive patients undergoing gastrointestinal endoscopic procedures were prospectively evaluated for the presence of risk factors for the development of infectious complications that indicated a need for prophylactic antibiotics. Criteria for the evaluation of risk factors were based on (a) former American Heart Association guidelines, (b) current American Heart Association guidelines, and (c) American Society for Gastrointestinal Endoscopy guidelines. Four hundred eighty-six patients underwent 507 procedures. Risk factors for the development of endocarditis or other infectious complications were found in 74 (15%) of all patients during the study period. Cardiac conditions in 51 patients were the most frequently encountered risk factor (69% of risk factors, 10% of all patients), with mitral valve prolapse in 25 patients accounting for 49% of patients with cardiac risk factors and 5% of all patients. Of the patients with mitral valve prolapse, 7 (28%, 1.4% of all study patients) had associated valvular regurgitation. None of the patients with mitral valve prolapse knew whether or not they had associated valvular regurgitation, and if they had had a previous echocardiogram, they were unaware of the results. Only 0.8% of patients had a prosthetic heart valve. The most common non-cardiac risk factor was the presence of a prosthetic joint (9 of 486, 1.8%). Of the 486 patients, 14 required antibiotic prophylaxis according to the above-mentioned guidelines. Six of the 14 patients were given either a non-recommended antibiotic or the wrong dose of a recommended antibiotic. CONCLUSIONS: (1) A decision regarding whether to administer antibiotic prophylaxis had to be made in 15% of patients undergoing endoscopy.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7988815 TI - A prospective evaluation of successful terminal ileum intubation during routine colonoscopy. AB - This study prospectively evaluated a dedicated effort to intubate the terminal ileum in an unselected population of patients undergoing colonoscopy in conjunction with our training program. The influence of the visual appearance of the terminal ileal mucosa on patient management was assessed subjectively. The cecum was reached in 270/295 (91%) patients, with successful terminal ileal intubation being accomplished in 213/270 (79%) examinations. The time required to intubate the terminal ileum (x = 3.4 minutes; range, 30 seconds to 10 minutes) was not significantly different (p < 0.05) between the several levels of training in our fellowship program. The terminal ileum was considered to be visually abnormal in 4 cases, but only 1 of these was abnormal on histologic examination. In this unselected population, routine ileoscopy was unrewarding for finding an incidental positive diagnosis; however, brief attempts at terminal ileal intubation may be useful to improve or maintain endoscopic skills, especially in a training setting. PMID- 7988817 TI - Colonoscopic features of colonic anastomoses. AB - Colonic anastomoses are frequently encountered, but their endoscopic features have never been adequately characterized. Results of 117 consecutive colonoscopies in patients with colonic anastomoses were prospectively studied during a 12-month period. Anastomoses were photographed, videotaped, and reviewed by the authors. The age range of patients was 18 to 87 years, and interval from surgery extended to 42 years. An equal number of right and left colonic resections were encountered; 9 patients had subtotal colectomies. Ninety-two anastomoses were hand-sewn, and 25 were stapled. Ileal pouch-anal anastomoses were not included. Nine common anastomotic features were identified with the following frequency of occurrence: neovascularity, 105 (89.7%); white anastomotic edge, 64 (54.7%); disruption of haustral pattern, 64 (54.7%); radial suture tracks, 35/92 (38.0%); exposed suture, 11/92 (11.9%); exposed staples, 6/25 (24%); scar tissue adjacent to anastomotic line, 8 (6.8%); nondistensibility of anastomosis, 5 (4.3%); blind colonic pouch, 10 (8.5%). No recurrent carcinomas were noted. The site of seven anastomoses (5.5%) could not be identified. Six of these patients underwent endoscopy more than 8 years postoperatively. Of the remaining 110 patients, 94 (85.5%) had between two and four of the above features identified. In three of four patients who required dilation because of strictures, neovascularity was not seen. We conclude that colonic anastomoses have characteristic endoscopic features. These features can be used as landmarks for definitive identification of anastomotic sites at colonoscopy. The lack of neovascularity at a colonic anastomosis may be an indicator of relative ischemia, predisposing to stricture formation. PMID- 7988816 TI - Endoscope-induced colitis: description, probable cause by glutaraldehyde, and prevention. AB - Six cases of acute, self-limited colitis that occurred after screening flexible sigmoidoscopy were deduced to be iatrogenic, probably caused by glutaraldehyde residues in the endoscopes after disinfection in an automatic disinfecting machine. The concentration of these residues was indirectly estimated by conductivity measurements of electrolyte concentration in the rinse-water tank of the disinfecting machine during and after five cycles and also in fluid remaining on the surface of the endoscopes and in the endoscope channels. After five cycles, residues in both the rinse water and fluid in the endoscope channels contained the equivalent of 0.2% glutaraldehyde. This was the result of a combination of technical and human errors. It can be prevented by changing the rinse water after each cycle, using forced air to dry the instruments, and washing the endoscopes before use. Users of the automatic disinfecting machine should be aware of the potential accumulation of toxic levels of residues that remain in endoscopes after disinfection. PMID- 7988818 TI - Endoscopic abnormalities of the anastomosis following resection of colonic neoplasm. AB - When 321 patients with resections for colonic neoplasms were prospectively evaluated for changes occurring at the anastomosis, eight different kinds were found (118 abnormalities seen in total). Inflammatory polyps, the most commonly observed abnormality (14.5%), may be misinterpreted as recurrent neoplasia by endoscopy. The majority of inflammatory polyps were discrete, 5- to 15-mm lesions, although diffuse nodularity was occasionally seen. Staples or sutures were visible at 11.3% of the anastomoses. Benign strictures, which developed in 7.1%, occurred primarily after left colonic resection with end-to-end anastomosis. Prominent vessels were occasionally seen at the anastomotic site (3.9%). Recurrent carcinoma at the anastomosis was found in 6 of 116 patients with Dukes B and C tumors (5.2%) and occurred 0.4 to 2.0 years after surgery (mean, 1.2 years). Recurrent carcinoma appeared as ulcerated submucosal lesions, bulky luminal masses, and polypoid lesions. In two patients, mucosal erythema, edema, and friability at the anastomosis were the only endoscopic evidence of underlying carcinoma. PMID- 7988819 TI - The natural history (fading time) of stigmata of recent hemorrhage in peptic ulcer disease. AB - From October 1991 to December 1992, 144 patients with bleeding peptic ulcer and stigmata of recent hemorrhage were included in a study designed to investigate, by means of endoscopic examinations repeated at 2-day intervals, the evolutionary development of stigmata of recent hemorrhage, such as visible vessels, and to determine the time required for each type of stigma to fade. Eighty-five patients underwent endoscopic follow-up until the stigmata had disappeared. A visible vessel takes about 4.1 +/- 2.1 days to disappear, requiring significantly more time than an adherent clot or an old stigma, which take 2.4 +/- 0.8 days and 2.4 +/- 1.3 days, respectively (p < .05). Bleeding does not recur after stigmata disappear. Time required for stigmata to fade is not affected by age, sex, smoking, history of peptic ulcer, ulcer location, severe bleeding, underlying systemic disease, or endoscopic local therapy. While healing, stigmata of recent hemorrhage evolve through a sequence of phases: a visible vessel may or may not appear as an adherent clot and then as a red or black flat spot before disappearing. PMID- 7988820 TI - Stent-guided sphincterotomy. AB - Performing sphincterotomy when either Billroth II gastrectomy or complicated periampullary diverticula are present may increase the risk of complications. In addition a sphincterotomy on the main pancreatic sphincter or the papilla of Santorini presents complicated problems. Stent-guided sphincterotomy has been utilized in 229 patients presenting to our institution from 1983 through 1992. They were performed in 67 patients who had undergone Billroth II gastrectomy, 23 with periampullary diverticula, 57 with pancreas divisum, and 82 with a history of recurrent pancreatitis. To prevent ductal injury or perforation, a stent is first inserted into the biliary or pancreatic duct to guide the sphincterotomy incision. The sphincterotomy is performed using electrocautery current delivered through a "needle knife" sphincterotome. Pancreatitis occurred in 19 patients (8.3%). It was mild in 17 and moderate in two patients. One patient experienced severe hemorrhage requiring surgery. No mortality or perforations occurred. The stent-guided needle knife sphincterotomy approach is an effective technique. It has a low complication rate even in these difficult anatomic conditions. It assures that the incision precisely follows the duct when performing pancreatic sphincterotomy. PMID- 7988821 TI - Endoscopic sphincterotomy for biliary pancreatitis: an alternative to cholecystectomy in high-risk patients. AB - Recurrent biliary pancreatitis frequently is associated with an intact gallbladder containing stones. This condition has been effectively treated by removing the gallbladder, but there is evidence that endoscopic sphincterotomy might obviate the need for cholecystectomy in some patients. We performed prophylactic sphincterotomy in 49 patients who presented with biliary pancreatitis more than once and who were considered at risk for surgery. The majority (39 patients) were treated electively after resolution of pancreatitis, while the remainder (10 patients) were treated urgently during their index admission because of continuing symptoms. No patient experienced recurrent pancreatitis over a mean follow-up period of 48 months. No mortality occurred in this endoscopic series, and no significant morbidity was experienced. Based on our results, we advocate performing sphincterotomy in the aged patient or younger patients considered at high risk for surgery who present with a history of recurrent pancreatitis and cholelithiasis. PMID- 7988822 TI - An in vitro comparison of biofilm formation on various biliary stent materials. AB - Stent occlusion may occur as the result of bacterial adherence and biofilm formation. This occlusion may be prompted by the material or design of the stents. In this study, a bile perfusion model was used to compare the biofilm formation on various stent materials. The copolymer and the wire mesh stents demonstrated less biofilm formation than the traditional stent. The development of new polymers may prolong stent patency. PMID- 7988823 TI - The watermelon stomach: long-term outcome in patients treated with Nd:YAG laser therapy. AB - Watermelon stomach is an unusual cause of gastrointestinal bleeding and iron deficiency anemia. Its etiology is unknown, but it has been reported to be associated with a variety of diseases, including autoimmune disorders and cirrhosis. We report on the long-term outcome of 15 patients (13 women, 2 men) treated with neodymium-yttrium-aluminum-garnet (Nd:YAG) laser therapy. The mean age of patients at presentation was 71.6 years (range, 59 to 85 years). Fourteen patients were transfusion-dependent, requiring an average of 9.6 units of blood in the 12 months preceding diagnosis and treatment. Associated diseases included scleroderma (3 patients), mixed connective tissue disease (1 patient), history of cancer (3 patients), cryptogenic cirrhosis (3 patients), and chronic renal failure (3 patients). In 7 of 9 patients who had an antinuclear antibody test, an elevated titer greater than 1:160 in a speckled pattern was noted. Nd:YAG laser coagulation therapy was administered to all patients without complications and was successful in reducing bleeding in every case. Five patients died during the course of follow-up without signs of recurrent gastrointestinal bleeding. The remaining 10 patients have had both endoscopic and hematologic improvement during a mean follow-up period of 4.4 years from the time of initial diagnosis (range, 2 to 8 years). The 10 survivors are no longer transfusion-dependent and have stable hematocrits. PMID- 7988824 TI - Visual "disappearing phenomenon" can reliably predict the nonadenomatous nature of rectal and rectosigmoid diminutive polyps at endoscopy. AB - Previous studies have failed to differentiate adenomatous from nonadenomatous diminutive polyps according to their gross macroscopic features at endoscopy. We prospectively evaluated the prevalence, distribution, and predictive value of a recently described morphologic feature-the "disappearing phenomenon"-in diminutive polyps of the distal 20 cm of the large bowel by studying 218 polyps in 90 consecutive patients. Disappearance was graded as complete, incomplete, or absent. Overall, complete disappearance was noted in 93 (43.1%) polyps, with a significantly higher prevalence in the middle and lower rectum (p < .05) and among smaller, paler, and smooth-surface polyps (p < .001). Incomplete disappearance was detected in both nonadenomas (23.1%) and adenomas (15.8%), but, more importantly, complete disappearance occurred in none of the 19 observed adenomas compared with 93 of 199 nonadenomas. Multiple logistic regression analysis revealed that disappearance was the strongest predictor (p < .001) of nonadenomatous histology among considered morphologic criteria. When complete disappearance was used to predict histologic type of diminutive polyps, its sensitivity was 100% and its specificity was 46.7%. In conclusion, the disappearing phenomenon represents a reliable visual marker for identifying nonadenomatous rectal and rectosigmoidal diminutive polyps at endoscopy. Diminutive polyps that disappear completely upon insufflation are invariably nonadenomatous and should not require endoscopic biopsy or removal. PMID- 7988825 TI - Endoscopic pancreatic duct sphincterotomy: indications, technique, and analysis of results. AB - Fifty-six patients, 54 of whom had chronic pancreatitis, underwent endoscopic pancreatic duct sphincterotomy during a 4-year period from 1988 to 1992. Acute complications noted in 10% of patients included exacerbation of pancreatitis (4) and cholangitis (2). Chronic complications included induction of asymptomatic ductal changes in 16%, thought to be related to endoprosthesis placement, and stenosis of the sphincterotomy site in 14%, requiring repeated endoscopic or surgical sphincter section. When combined with a number of ancillary procedures, including removal of obstructing ductal calculi and stent placement for ductal disruption or stenosis, pancreatic duct sphincterotomy was associated with amelioration of chronic pain or decreased number of clinical attacks of pancreatitis in a subset of patients. The authors conclude that endoscopic pancreatic duct sphincterotomy enlarges our endotherapeutic armamentarium and deserves additional evaluation. PMID- 7988826 TI - Gastric mucosal bleeding time in cirrhosis. AB - Gastric mucosal bleeding time was measured prospectively in 25 patients with cirrhosis and portal hypertension undergoing routine sclerotherapy. Age and sex matched controls without liver disease were also studied. Correlations were sought between gastric mucosal bleeding time and age, platelet count, prothrombin time, skin bleeding time, Child-Pugh score, variceal size before sclerotherapy, and degree of portal hypertensive gastropathy. Gastric bleeding time was prolonged in 12% of the patients with cirrhosis (mean, 3.24 minutes; SEM, 0.476) and in none of the controls (mean, 3.0; SEM, 0.171). No correlation was noted between gastric bleeding time and any of the above variables. The results of this study indicate that gastric mucosal bleeding time is prolonged in cirrhosis but is an independent physiologic parameter unrelated to any of the above-mentioned variables. PMID- 7988827 TI - Evaluation of upper gastrointestinal tumors with a new endoscopic ultrasound probe. PMID- 7988828 TI - Treatment of high-risk patients with symptomatic cholelithiasis by endoscopic gallbladder stenting. PMID- 7988829 TI - The occlusion rate of pancreatic stents. PMID- 7988830 TI - Computer-assisted data processing of images of mucosal and submucosal blood vessels of the stomach obtained by visible and infrared endoscopy using a directional-contrast filter. PMID- 7988831 TI - Colonic mucosal appearance of Tangier disease in a new patient. PMID- 7988832 TI - Esophageal ectopic sebaceous glands: endoscopic and histologic findings. PMID- 7988833 TI - Mucinous cystadenocarcinoma of the pancreas: an uncommon presentation with hemobilia. PMID- 7988834 TI - A method for removing meat impactions from the esophagus. PMID- 7988835 TI - Endoscopic diagnosis of common bile duct varices by percutaneous trans-hepatic choledochoscopy: differential diagnosis from bile duct carcinoma. PMID- 7988836 TI - Gastritis cystica profunda presenting as giant gastric mucosal folds: the role of endoscopic ultrasonography and mucosectomy in the diagnostic work-up. PMID- 7988837 TI - Antibiotic prophylaxis for gastrointestinal procedures: who needs it? PMID- 7988838 TI - Common ground for endoscopic interventionists. PMID- 7988839 TI - The non-bleeding vessel: is the optical interpretation true? PMID- 7988840 TI - Cytomegalovirus induced esophageal ulceration. PMID- 7988841 TI - Failure to deflate the balloon of replacement gastrostomy tubes. PMID- 7988842 TI - Pseudo stroke after an ERCP. PMID- 7988843 TI - Endoscopic stent exchange. PMID- 7988844 TI - Laparoscopic percutaneous gastrostomy. PMID- 7988845 TI - Improved technique for the Soehendra stent extractor. PMID- 7988846 TI - Uncommon endoscopic appearance of gastric mucosal ectopia in the rectum. PMID- 7988847 TI - Failure of colonoscopic surveillance in ulcerative colitis. PMID- 7988848 TI - Bleeding peptic ulcer--risk factors for rebleeding and sequential changes in endoscopic findings. PMID- 7988849 TI - [When may, should, must the ovary by removed--with which technique?]. AB - The growing demand for minimally invasive operative processes and the unmistakable progress in pelviscopy, have led to an extension of the indications for minimally invasive surgery. At the same time, the operative treatment of ovarian cysts is the third most frequently performed pelviscopic operation. The indication for ovarectomy depends, above all, on anamnestic factors, the clinical findings and the results of pre-operative vaginal sonography. In the event of inadequate hormone secretion by the ovaries, the indication for organ removal should be generously applied. Vaginal sonography is not capable of proving or excluding the existence of a malignancy with 100% certainty. The average rate of ovarian carcinomas is 2.6% in case of smooth-walled, unicamerate cysts. Pelviscopy is also unable to differentiate reliably between benign and malignant ovarian tumours. With the aid of pelviscopic operative processes, a cystic ovarian tumour cannot be extirpated in toto with the necessary certainty. In spite of the conflicting results in the literature, an iatrogenic rupture of an early ovarian carcinoma can be expected to result in worsening the prognosis. The Department of Obstet. Gynecol. University of Gottingen, adopted the following procedure: 1. A (mini-) laparotomy with immediate section for microscopic examination is always performed on sonographically suspect ovarian tumours. 2. On smooth-walled unicamerate ovarian tumours > or = 3 cm which persist or fail to respond to treatment with oral contraceptives, (mini-) laparotomy is performed with complete extirpation of the cystic ovarian tumour and immediate section for microscopic examination; a conceivable alternative is, if possible, total pelviscopic extirpation of the ovarian cyst with immediate section for microscopic examination.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7988850 TI - [Does rupture of a mucinous cystoma of the ovary result in the development of pseudomyxoma peritonei?]. PMID- 7988851 TI - [Hysteroscopic endometrium ablation to avoid hysterectomy in "high risk" patients]. AB - Hysteroscopic endometrial ablation under maximal anaesthesiological surveillance was performed in 34 high-risk patients to avoid hysterectomy. It was a collective of patients with heavy thrombo-embolic or thrombotic disease, either under permanent anticoagulation due to residual disease or multiple endoprosthetic treatment, or with endogenous coagulopathy. In all these women, hysterectomy was either a relative or an absolute contraindication. In 22 patients, treatment resulted in complete amenorrhoea or at least hypomenorrhoea (without menometrorrhagia) respectively cyclic spotting. In 6 further patients, amenorrhoea was achieved after a repeat procedure. Endometrial ablation was thus successful in 28 of 34 cases. In these patients, hysterectomy with the risk of major or even lethal complications, could thus be avoided. Hysterectomy, however, had to be performed in 2 women with extensive adenomyosis uteri interna. Within two respectively three years after endometrial ablation, two other patients died from causes unrelated to the surgical intervention (cardiac infarction, cerebral haemorrhage). Follow-up ranged from 1 to 5 years. Hysteroscopic endometrial ablation proved an effective therapeutic option in this selected group of patients. Other indications require further study. PMID- 7988852 TI - [Clomiphene resistant PCO syndrome: IVF treatment as an alternative in failed gonadotropin treatment]. AB - 34 infertile patients with severe clomiphene-resistant polycystic ovary syndrome were treated with IVF/ET. Stimulation attempts with gonadotropins had resulted in multifollicular ovarian reactions, which did not allow standard ovulation induction using hCG due to the risk of multiple pregnancy. The resulting oocyte retrieval rates (87.4%/treatment cycle), embryo transfer rates (73.3%/oocyte retrieval) and pregnancy rates (24.2%/embryo transfer) approximately corresponded to the rates which are achieved in women with tubal failure using IVF/ET. Since strictly a maximum of 2 embryos was transferred, the occurrence of multiple pregnancies of higher degree could be avoided as opposed to standard gonadotropin therapy. The treatment so far only resulted in singleton pregnancies. The relatively high ovarian hyperstimulation rate (34.4%, primarily WHO stage I-II) could not be unequivocally lowered even by aspiration of all larger follicles. PMID- 7988853 TI - [400 cycles with assisted fertilization in severe teratozoospermia]. AB - From May 1991 to July 1993, assisted fertilisation by micromanipulation (PZD, SUZI and ICSI) was performed in 397 cycles with severe teratozoospermia. In the second series of 152 cycles with SUZI, the pregnancy rate per cycle was 5% (10% per transfer). In the third series, the method was changed from SUZI to ICSI. PMID- 7988854 TI - [GnRH agonist treatment for in vitro fertilization in hyperandrogenemia]. AB - Luteinising hormone (LH) is essential for steroidogenesis and folliculogenesis. In hyperandrogenic patients, however, an increased androgen production with the consecutive development of polycystic ovaries is caused by elevated LH levels. Suppression of androgens by the use of a GnRH agonist (a) may be a causal therapeutic approach. Therefore, we initiated a study comparing the combined GnRHa/HMG stimulation with HMG alone in hyperandrogenic patients undergoing in vitro fertilisation (IVF). Altogether, 62 cycles were treated. Group 1 (n = 33) received a single depot injection of 3.6 mg goserelin on cycle day 22 followed by individualised HMG stimulation 14 days later. Group 2 (n = 29) started with the HMG stimulation on cycle day 3. In group 1, a pregnancy rate per transfer of 36.4% was achieved compared to only 20% in group 2. There was a strikingly lower abortion rate in group 1 that resulted in a significantly higher on going pregnancy rate. The results are in favour of the combined GnRHa/HMG stimulation as a first line therapy for hyperandrogenic IVF patients. PMID- 7988855 TI - [Transposition of the fallopian tube as a therapeutic possibility in special cases of tubal sterility]. AB - This is a report on a new method of microsurgical transposition of the Fallopian tube. It was developed to deal with congenital malformations or with the different anatomic remnants after pelvic surgery or pelvic inflammatory diseases. The tube is mobilised by severing the mesosalpinx with the unipolar microelectrode without damaging the longitudinal vessels. After mobilisation, the bends of the tube disappear and the length increases almost doublefold. Then the tube can be laid to the contralateral ovary without any tension. The tube must be fixed to the ovary in such a way, that the fimbrial end is mobile enough to lay onto the ovary during ovulation. Up to now, six patients with longstanding tubal sterility were operated upon. Three of them became pregnant, one twice. There were no ectopic pregnancies and no abortions. PMID- 7988856 TI - [Pregnancy-induced trophoblast diseases--results from the years 1976-1992]. AB - INTRODUCTION: Gestational trophoblastic diseases (GTD) represent a spectrum of different disorders, derived from the human placental trophoblast. GTDs are potentially fatal disorders and are of great importance for gynaecologists and pathologists. STUDY DESIGN: In recent years 148 GTDs were treated at department of Obstetrics and Gynaecology of Leipzig University. We reexamined these cases with respect to diagnostic findings, diagnostic mistakes, the necessity of consecutive chemotherapy and outcome. RESULTS: The 148 relevant cases included 103 complete hydatidiform moles, 13 invasive moles and 32 choriocarcinomas. 61.5% showed a spontaneous regression of HCG after molar evacuation. 57 cases developed persistent trophoblastic disease with consecutive mono-combined or polychemotherapy. An overall remission rate of 91.2% was achieved. The two patients, who died, showed a late stage of disease. 5.3% of the cases had a recurrence of disease. The most frequent side effect of chemotherapy was a moderate bone marrow depression in 58% of cases. 88.5% were diagnosed by suction curettage alone. Twelve patients had an operative intervention before chemotherapy, often due to diagnostic misinterpretation of the symptoms. Eight cases needed a secondary operation to attain complete remission. CONCLUSIONS: Initiating chemotherapy is very important for therapy success. In cases of complete hydatidiform mole, it is difficult to make a prognostic statement with reference to biological behaviour of the disease by morphological methods alone. The difficulties are discussed. These cases emphasise the need for appropriate clinical monitoring and close cooperation between the gynaecologist, the pathologist and the clinician. PMID- 7988857 TI - [Diagnosis of urinary tract infections in puerperium]. AB - Urinary tract infections (UTI) are the most frequent nosocomial infections of women during puerperium. Since, in these women, diagnostic accuracy is affected by lochial secretion, suprapubic urinary bladder puncture (SPB) is recommended. Between December 1989 and January 1993, we subjected 903 women to suprapubic urinary bladder puncture (SpBP) at the 4th or 5th day after delivery. A urine culture of SpBP was done in all cases. Semiquantitative leukocyte counts (n = 891) and nitrite test (n = 830) were done on mid-stream urine (MSU). Side by side with microbiological investigation for urinary tract pathogens via SpPB, MSU was performed in 246 cases immediately after SpPB had been carried out. Leukocyte counts were also estimated in SpBP urine samples. In 370 (41.1%) of 903 SpBP, one or more microorganisms were cultivated. Only 36 (4.0%) of 903 women showed UTI symptoms. Microorganisms were detectable via SpBP in only 26 (72.7%) of these 36 symptomatic patients. Vaginal-operative or secondary caesarean section are related to an increased UTI rate (p < 0.001). UTI were also significantly (p < 0.0001) more frequent in women subjected to catheterisation sub partu (54.5%) compared to no catheterism (24.4%). No significant differences between the number of leukocytes in MSU sediment and the SpBP findings were seen. Semiquantitative leukocyte counts in SpBP offered a significantly (p < 0.001) increased number of leukocytes in cases with microorganism detection in SpBP irrespective of MSU findings. These results justify the designation of uterine tract infection also in the absence of complaints as "infection" and not common "bacteriuria".(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7988858 TI - [The birthing stool--an obstetrical risk?]. AB - During 1992, 140 women out of a total of 1122 used the delivery chair at the department for obstetrics and gynaecology at the LKH Modling. We compared them to a control group in the supine position. In order to evaluate the safety of deliveries on the delivery chair, we studied the duration of the stages of labour, rate and degree of soft tissue injuries, maternal blood loss, fetal outcome and complications in the puerperium. The use of the delivery chair showed no increased risk to either the mother or the fetus and therefore represents an appropriate alternative to the traditional supine position for delivery. PMID- 7988860 TI - [Intrauterine fetal death in acute toxoplasmosis infection]. AB - This is a report on a rare incident of an intrauterine foetal death with toxoplasmosis in the 25th week of pregnancy. The diagnosis could be made serologically as well as pathologically. The issues connected with serological screening for toxoplasmosis are discussed on the basis of this case. PMID- 7988859 TI - [Injury to the surgeon in treatment of an HIV infected patient]. AB - The number of HIV-infected female patients undergoing surgery is increasing. Injuries of the surgeon can never be completely excluded. The risk of HIV infection via a needle puncture lesion is estimated to be approximately 0.4%. Besides the well-known protective measures, careful wound disinfection followed by HIV tests for a period of up to six month after the lesion are indicated. It is indeed high time to consider the patient HIV test as a matter of course, not least because it is our duty to be concerned also about the health of our co workers and staff directly engaged in patient care. PMID- 7988861 TI - [Tuberculous meningoencephalitis in post-embryo transfer status]. AB - A 30-year old pregnant woman, who received an embryo transfer, suffered since the 12th week of pregnancy from therapy-resistant attacks of fever for several weeks. With progressive deterioration, the increasingly somnolent patient showed by now clear signs of meningism and acid-fast bacilli were found in the cerebrospinal fluid. NMR showed a finding consistent with bacterial meningoencephalitis. During therapy with INH, Rifa and EMB, the clinical course and the CSF findings showed rapid improvement. Nevertheless, spontaneous abortion occurred in the 23rd week of pregnancy. Previous history revealed, that granulomatous salpingitis had been diagnosed several years earlier as the reason for infertility. PMID- 7988862 TI - Membrane-bound Bacillus cytochromes c and their phylogenetic position among bacterial class I cytochromes c. AB - Gram-positive bacteria lack a periplasmic compartment and contain only membrane bound cytochromes c. There are at least two types. One is found in subunit II of cytochrome oxidase, and the other is small cytochrome c which is also membrane bound because of an unprocessed signal sequence or post-translational acylation at the N-terminal end of the protein. These Bacillus cytochromes c are compared with known class I cytochromes c, and a phylogenetic tree has been constructed by the neighbour-joining method. PMID- 7988863 TI - Pentose transport by the ruminal bacterium Butyrivibrio fibrisolvens. AB - Butyrivibrio fibrisolvens is a fibrolytic ruminal bacterium that degrades hemicellulose and ferments the resulting pentose sugars. Washed cells of strain D1 accumulated radiolabelled xylose (Km = 1.5 microM) and arabinose (Km = 0.2 microM) when the organism was grown on xylose, arabinose, or glucose, but cultures grown on sucrose or cellobiose had little capacity to transport pentose. Glucose and xylose inhibited transport of each other non-competitively. Both sugars were utilized preferentially over arabinose, but since they did not inhibit transport of arabinose, it appeared that the preference was related to an internal metabolic step. Although the protonmotive force was completely abolished by ionophores, cells retained some ability to transport pentose. In contrast, the metabolic inhibitors iodoacetate, arsenate, and fluoride had little effect on protonmotive force but caused a large decrease in intracellular ATP and xylose and arabinose uptake. These results suggested that high-affinity, ATP-dependent mechanisms were responsible for pentose transport and hexose sugars affected the utilization of xylose and arabinose. PMID- 7988864 TI - Investigation of the role of sterol delta 8-->7-isomerase in the sensitivity of Saccharomyces cerevisiae to fenpropimorph. AB - Treatment of Saccharomyces cerevisiae with the morpholine fungicide fenpropimorph was examined using both a wild-type and a mutant strain (erg2) defective in sterol delta 8-->7-isomerase. No resistance to fenpropimorph was observed in the mutant strain after 3 days, although after 7 days the mutant and the wild-type strains had grown in concentrations of fenpropimorph close to the saturating dose. Re-inoculation of both strains into fresh medium containing fenpropimorph resulted in continued growth and this adaptation to fungicide tolerance was lost on subculture in the absence of fenpropimorph. Analysis of the sterols present in the cells indicated that fenpropimorph treatment resulted in the accumulation of delta 8,14-sterols. This accumulation and the corresponding depletion of ergosterol were correlated with growth inhibition rather than the presence of delta 8-sterols. Together with an absence of gene dosage effect for ERG2 on fenpropimorph sensitivity, this supports the hypothesis that sterol delta 8-->7 isomerase inhibition does not contribute to the fungicidal activity of fenpropimorph. PMID- 7988865 TI - Bidirectional gene transfer between Aspergillus fumigatus and Aspergillus nidulans. AB - A genomic DNA library was constructed from a pathogenic strain of Aspergillus fumigatus using the cosmid vector pCosAX. Cosmid clones with homologies to the rodA, brlA, fluG, flbA or trpC genes from A. nidulans were isolated from the library. Each A. fumigatus clone was used to complement a strain of A. nidulans with a mutation in the homologous gene. A spontaneous white spored strain of A. fumigatus was isolated. The mutation was complemented by transforming the strain with a plasmid containing the wA gene from A. nidulans. The results from these experiments indicate a significant degree of structural and functional homology between genes from the organisms. These findings indicate the potential to exploit the methods and information available from A. nidulans to address questions related to human disease caused by A. fumigatus and the ability to use A. nidulans as a surrogate genetic host for characterizing A. fumigatus gene function. PMID- 7988866 TI - Chromate reductase activity of Enterobacter aerogenes is induced by nitrite. AB - A chromate resistant mutant of Enterobacter aerogenes manifested its chromate resistance only under aerobic conditions. Both parent and mutant showed substantial levels of anaerobic chromate reductase activity when grown on glycerol plus fumarate. The chromate reductase was further induced by growth in the presence of nitrite but was repressed by nitrate. The chromate reductase activity paralleled that of the formate-linked nitrite reductase. There was no significant difference in chromate reductase levels between the parent and its chromate resistant mutant, indicating that this enzyme activity is not, in fact responsible for chromate resistance as was suggested previously by others. PMID- 7988867 TI - Cytotoxin-converting phages, phi CTX and PS21, are R pyocin-related phages. AB - phi CTX is a temperate phage of Pseudomonas aeruginosa harbouring the ctx gene that encodes cytotoxin (CTX). We identified phi CTX as an R pyocin-related phage, by serological and molecular analysis, based on the findings that the infectivity of the phage was inhibited with the antisera directed R pyocins and R pyocin related phages and that the phi CTX genome showed DNA homology to the genome of PS17 (a representative of the R pyocin-related phages) as well as to the pyocin R2 genes. Another new CTX-converting, R pyocin-related phage named PS21 was isolated from a CTX-producing strain of P. aeruginosa, suggesting the distribution of the ctx gene by certain members of R pyocin-related phage family. PMID- 7988868 TI - Isolation of OprM-deficient mutants of Pseudomonas aeruginosa by transposon insertion mutagenesis: evidence of involvement in multiple antibiotic resistance. AB - Overproduction of the Pseudomonas aeruginosa outer membrane protein OprM was observed in the nalidixix acid (NalB-type) multidrug-resistant strains. To clarify the involvement of OprM in the resistance, transposon mutants were isolated from strain PAO4141 and its OprM-overexpressed mutant KG2113 and were screened for OprM production by immunoblot assays using murine polyclonal antiserum resulting from immunization with purified OprM. Two OprM-deficient mutants from PAO4141 and one from KG2113 were identified. Determination of the susceptibilities of these mutants to antimicrobial agents demonstrated that OprM was involved not only in the acquired resistance, but also in the intrinsic resistance of P. aeruginosa to quinolones, cephems, penicillins, tetracycline, and chloramphenicol. PMID- 7988870 TI - Comparative analysis of gene expression in Streptococcus pneumoniae and Lactococcus lactis. AB - The pFL10 plasmid vector for translational fusions was constructed. pFL10 is based in the promiscuous pLS1 replicon and contains the pC194 cat gene deprived of its transcriptional promoter and Shine-Dalgarno (SD) sequence. Three promoters (Pcit, PpolA and PtetL) from Gram-positive bacteria, inserted in pFL10, were tested for their ability to drive transcription in Lactococcus lactis and Streptococcus pneumoniae. These promoters were coupled to the SD sequence of the lactococcal citP gene fused to the cat gene. Determination of the 5' ends of the three mRNAs by primer extension revealed the same start sites in both bacterial systems. However, it was observed a differential efficiency of promoter utilization by the RNA polymerases from the two hosts. The transcriptional behavior correlates with expression of the cat gene measured by determinations of chloramphenicol acetyltransferase (CAT) activity. Substitution of the SD of citP by that of the T7 phi 10 gene rendered a similar decrease of the CAT production in both bacterial systems. PMID- 7988871 TI - Binding protein for Escherichia coli heat-stable enterotoxin II in mouse intestinal membrane. AB - The protein binding Escherichia coli heat-stable enterotoxin II (STII) was isolated from cell membranes of mouse intestine. The binding of 125I-labeled STII to the proteins was inhibited by unlabeled STII, showing that it is specific. Proteins cross-linked with 125I-STII were purified by column chromatography on hydroxyapatite and TSK gel. Analyses of the purified protein by SDS polyacrylamide gel electrophoresis and gel filtration showed that the molecular mass was 25 kDa. PMID- 7988869 TI - Stimulation of Escherichia coli F-18Col- type-1 fimbriae synthesis by leuX. AB - Escherichia coli F-18, a normal human fecal isolate, is an excellent colonizer of the streptomycin-treated mouse large intestine. E. coli F-18Col-, a derivative of E. coli F-18 which no longer makes the E. coli F-18 colicin, colonizes the large intestine as well as E. coli F-18 when fed to mice alone but is eliminated when fed together with E. coli F-18. Recently we randomly cloned E. coli F-18 DNA into E. coli F-18Col- and let the mouse intestine select the best colonizer. In this way, we isolated a 6.5-kb E. coli F-18 DNA sequence that simultaneously stimulated synthesis of type 1 fimbriae and enhanced E. coli F-18Col- colonizing ability. In the present investigation we show that the gene responsible for stimulation of type 1 fimbriae synthesis appears to be leuX, which encodes a tRNA specific for the rare leucine codon UUG. Moreover, it appears that expression of leuX may be regulated by two proteins (22 kDa and 26 kDa) encoded by genes immediately adjacent to leuX. PMID- 7988872 TI - Transcriptional regulation of the Trichoderma longibrachiatum egl1 gene. AB - Transcription of the Trichoderma longibrachiatum egl1 gene is induced in the presence of lactose and beta-methylglucoside and repressed by glucose. A DNA fragment containing 722 bp upstream of the ATG codon has been sequenced. The gene has two major transcription start points (20 and 24 nucleotides upstream from the ATG codon) and several transcription termination points (located in a region around 130 nt downstream of the stop codon). Two 6-mer sequences (5'-CTGGAG-3') separated by 16 bp are present in the egl1 gene promoter. These sequences match the Aspergillus nidulans consensus CreA binding site and might be implicated in carbon catabolite repression of egl1 transcription. PMID- 7988873 TI - Evidence for the location of OprM in the Pseudomonas aeruginosa outer membrane. AB - OprM with a M(r) of 49 K is associated with the multidrug resistance of Pseudomonas aeruginosa. Detergent fractionation of bacterial cells has demonstrated that OprM is located in the outer membrane from which it sediments with the other major outer membrane proteins. In this study we have determined the location of OprM as the P. aeruginosa outer membrane. Western immunoblots of cell fractions, obtained by sucrose density gradient centrifugation of whole cell lysates, were probed with an OprM-specific murine polyclonal antiserum. PMID- 7988874 TI - Increases in the intracellular concentration of glycerol during development in Myxococcus xanthus. AB - The role of glycerol as a natural morphogen of myxospore formation in Myxococcus xanthus was examined. Glycerol was extracted from cells undergoing development and analyzed by gas chromatography. Glycerol is present in cells, and the intracellular level undergoes a series of transient increases during development. The data suggest a role for glycerol in myxosporulation and fruiting body morphogenesis, supporting the notion that this chemical induction of sporulation may represent a physiological pathway in development. PMID- 7988875 TI - Insertion of a 27 amino acid viral peptide in different zones of Escherichia coli beta-galactosidase: effects on the enzyme activity. AB - Seven internal, putatively exposed regions of Escherichia coli beta-galactosidase have been explored regarding their tolerance to insertions of large foreign peptides. Small sequence modifications, including amino acid substitutions and small deletions, were introduced into the lacZ gene to generate unique BamHI restriction sites. By using these mutant genes, a 27 amino acid stretch reproducing the hypervariable loop of foot-and-mouth disease virus VP1 protein (site A) was further inserted in predefined regions of the enzyme. Among the 13 resulting engineered proteins only three, carrying sequence modifications within a short region, are active, with only moderate reduction of their specific activities. The identified permissive region, which involves amino acids 275 to 279, seems to be a flexible area that could be appropriate to incorporate and study biological properties of heterologous peptides in correctly folded beta galactosidase chimeric proteins. PMID- 7988876 TI - Mycobacterial cell wall: structure and role in natural resistance to antibiotics. AB - Mycobacteria show a high degree of intrinsic resistance to most antibiotics and chemotherapeutic agents. The low permeability of the mycobacterial cell wall, with its unusual structure, is now known to be a major factor in this resistance. Thus hydrophilic agents cross the cell wall slowly because the mycobacterial porin is inefficient in allowing the permeation of solutes and exists in low concentration. Lipophilic agents are presumably slowed down by the lipid bilayer which is of unusually low fluidity and abnormal thickness. Nevertheless, the cell wall barrier alone cannot produce significant levels of drug resistance, which requires synergistic contribution from a second factor, such as the enzymatic inactivation of drugs. PMID- 7988877 TI - The 32-kDa glycoprotein of Chlamydia trachomatis is an acidic protein that may be involved in the attachment process. AB - The 32-kDa glycoprotein of Chlamydia trachomatis was shown to have a pI of 6.2 to 6.4 which distinguished this protein from the chlamydial histone-like protein of similar molecular mass that has a pI of > 10. The initial interaction of the glycan of 32 kDa glycoprotein and HeLa cells was also investigated. Glycan was cleaved from the protein backbone by N-glycanase and radiolabeled with tritium by sodium borohydride reduction. Competition assays showed the binding of glycan to HeLa cells was inhibited by galactose, mannose, and N-acetylglucosamine but not by sedoheptulose and fructose. Untreated and UV-treated organisms inhibited the binding, while heat-inactivated organisms did not. Binding was blocked by rabbit antiserum against whole organisms but not by rabbit anti-155-kDa antiserum or monoclonal antibodies against the lipopolysaccharide and major outer membrane protein. PMID- 7988878 TI - The 126 kDa iron-regulated protein of Listeria monocytogenes is not a transferrin binding protein. AB - It has been reported that a 126 kDa protein of Listeria monocytogenes binds human transferrin. It is evident from results presented here that this is not so and that the observation of others resulted from interaction of this 126 kDa protein with streptavidin. PMID- 7988879 TI - Role of rpoS in the regulation of Salmonella plasmid virulence (spv) genes. AB - Salmonella plasmid virulence (spv) genes are organized into two transcriptional units: one formed by the spvR gene and the other by the spvA, spvB, spvC and spvD genes. Transcription of both units is activated by SpvR, a regulatory protein of the LysR family. The effect of RpoS, a stationary phase-associated sigma factor, on the expression of spv genes was studied using lacZ transcriptional fusions to spvR and spvA in wild-type and rpoS Escherichia coli backgrounds. Mutant and wild type SpvR proteins were expressed in trans from a multicopy plasmid. The results show that the combined action of rpoS and spvR is necessary for transcription of spvA and that this combination also enhances transcription of spvR. Interestingly, spvR can also be transcribed in an alternative manner, i.e. in the absence of rpoS or spvR or both. The possible role for SpvR as a repressor of its own transcription is discussed. PMID- 7988880 TI - Structural mannoproteins released by beta-elimination from Candida albicans cell walls. AB - Mild alkaline solutions (beta-elimination), after removing the non-covalently bonded wall materials by hot SDS, released 13% and 26% of remaining wall proteins from mycelial and yeast cells of Candida albicans, respectively. When the beta elimination was carried out after digestion of the walls with chitinase, four fold more proteinaceous materials were released from mycelium and a similar amount in yeast walls. The solubilized materials were shown to be highly polydisperse, and endo-glycosidase H reduced their polydispersity and molecular masses, revealing different electrophoretic patterns in yeast and mycelial cell walls. The solubilized mycelial proteins carried N-glycosidic sugar chains and the epitopes recognized by two monoclonal antibodies were preserved, although showing a different behaviour in yeast walls. These results are consistent with the idea that significant amounts of intrinsic O-glycosylated mannoproteins are interconnected in the walls of C. albicans. PMID- 7988882 TI - Sizing the Fusobacterium nucleatum genome by pulsed-field gel electrophoresis. AB - The genome sizes of Fusobacterium nucleatum strains F1, F3, F6, ATCC 10953, ATCC 25586 and Fev1 were determined by pulsed-field gel electrophoresis (PFGE). The restriction enzymes SmaI, SacII,SalI and XhoI were found to generate a reasonable number of DNA fragments which could be separated by PFGE in agarose gels. The apparent chromosomal lengths of the F. nucleatum strains were determined to be approximately 2.4 million base pairs. This was within the size-range found by experiments exploiting renaturation kinetics. PMID- 7988883 TI - Peptidase D of Escherichia coli K-12, a metallopeptidase of low substrate specificity. AB - Peptidase D of Escherichia coli was overproduced from a multicopy plasmid and purified to electrophoretic homogeneity. The pure enzyme was stable at 4 degrees C or -20 degrees C and had a pH optimum at pH 9, and a pI of 4.7; the temperature optimum was at 37 degrees C. As the enzyme was activated by Co2+ and Zn2+, and deactivated by metal chelators, it appears to be a metallopeptidase. By activity staining of native gels, 11 dipeptides which are preferentially cleaved by peptidase D were identified. Peptidase D activity required dipeptide substrates with an unblocked amino terminus and the amino group in the alpha or beta position. Non-protein amino acids and proline were not accepted in the C-terminal position, whereas some dipeptide amides and formyl amino acids were hydrolyzed. Km values of 2 to 5 mM indicate a relatively poor interaction of the enzyme with its substrates. PMID- 7988881 TI - Nutritional upshift response of ribosomal protein gene transcription in Saccharomyces cerevisiae. AB - Switching Saccharomyces cerevisiae from non-fermentative to fermentative growth by adding glucose to a medium with glycerol as the sole carbon source, leads to a sudden increase in the rate of ribosomal protein gene transcription. By analyzing the nutritional shift response in a variety of yeast mutants and in the presence of different drugs, evidence was obtained that: (i) no de novo protein synthesis is required for this response; (ii) protein kinase A is essential, though independent of intracellular levels of cAMP, whereas protein kinase C is not involved; (iii) proper regulation of sugar phosphorylation is essential; (iv) glycolysis is required for the long term effect of the nutritional upshift; and (v) pathways leading to glucose-induced activation differ from those leading to gene repression, probably already at the level of glucose transport. PMID- 7988884 TI - DNA intercalating drugs inhibit positive supercoiling induced by novobiocin in halophilic archaea. AB - The two DNA intercalators, actinomycin D and 2-methyl-9-hydroxy-ellipticine, and the DNA minor groove ligant DAPI inhibited the growth of the haloarchaeon Halobacterium sp. GRB and bind to its plasmid pGRB-1. In contrast to specific DNA topoisomerase II inhibitors, they produced neither double-stranded breaks nor relaxation of plasmidic DNA. The two DNA intercalators inhibited positive supercoiling induced by novobiocin, suggesting that positive supercoiling in haloarchaea is due to transcription, as in the domain Bacteria. Plasmids from haloarchaea could thus be used to prescreen for DNA intercalators and to discriminate between different drug families via their mode of action. PMID- 7988885 TI - Genetic diversity of the Helicobacter pylori haemagglutinin/protease (hap) gene. AB - Helicobacter pylori has been associated with the etiology of gastritis, gastric and duodenal ulcers and gastric cancer in man. In this study we confirm the presence of the haemagglutinin/protease (hap) gene in ten geographically diverse strains of H. pylori, but the Southern analysis of genomic DNA suggested that the location of the hap gene was different in each strain. We suggest that the hap gene is subject to a high rate of mutation and subsequent polymorphisms by virtue of a mobile, genetic element located upstream of the hap gene in the H. pylori genome. Simple transformation experiments suggested that this polymorphism may be mediated by a transposon-like element. PMID- 7988886 TI - Morphology of the viable but nonculturable Vibrio cholerae as determined by the freeze fixation technique. AB - The morphology of the nonculturable Vibrio cholerae strain TSI-4 was examined by the freeze fixation technique of electron microscopy and subsequently four unique structures were found in the fine structure s of this bacterium. The size of the cell was about 2/3 of the growing cell. Although the cell was observed to have an outer membrane as well as the cell membrane and cytoplasm, the outer membrane was undulated and had a surface layer of fine fibers. The peptidoglycan layer was thick and more electron dense than that of normal cells. PMID- 7988887 TI - Cloning and sequencing of the gene encoding Vibrio cholerae O1 fimbrial subunit (fimbrillin). AB - The gene encoding an 18 kDa fimbrial subunit of Vibrio cholerae O1 was identified in a fimbriate strain Bgd17. Mixed oligoprimers were prepared based on the amino acid sequence of the N-terminus and that from a cyanogen bromide-cleaved fragment of the fimbrillin. A PCR-amplified 185 bp DNA fragment was sequenced. This 185 bp fragment was further extended to 540 bp to 3' and 5' termini by RNA-PCR using a primer containing a random hexamer at its 3' end. This fragment did not contain the stop codons. It was further extended by a gene walking method using Eco RI cassette and its primers. Finally a 660 bp fragment was obtained and sequenced. This fragment contained the complete open reading frame of the structural subunit of the fimbriae, composed of 169 amino acids with a molecular mass of 17435.65 and a leader sequence of 6 or 9 amino acids. The deduced amino acid sequence of the polypeptide encoded by the gene, designated fimA, displayed a highly conserved sequence of MKXXXGFTLI EL of type 4 fimbriae. PMID- 7988888 TI - Low-copy-number T7 vectors for selective gene expression and efficient protein overproduction in Escherichia coli. AB - A set of low-copy-number vectors (pPD) has been constructed that permit selective gene expression and high-level protein overproduction in Escherichia coli, based on the bacteriophage T7 RNA polymerase/T7 promoter system. These plasmids carry a chloramphenicol resistance gene (cat) as a selective marker and an extended multiple cloning site for convenient gene cloning. Their replication is mediated by ori sequences derived from the low-copy-number vector pSC101. The efficient T7 gene 10 promoter present on these vectors allows selective and high-level transcription of cloned genes carrying their own translational initiation signals. In addition, low-copy-number T7 vectors were constructed that permit expression of genes lacking their own transcription and translation initiation elements by providing a ribosome binding site, an ATG start codon and a multiple cloning site devised for the cloning in all three reading frames. The pPD expression vectors were used to achieve high-level overproduction of the E. coli integral outer membrane protein Tsx, and the cytoplasmic enzymes beta galactosidase (beta Gal) and UTP:alpha-D-glucose-1-phosphate uridylyltransferase (GalU). The characteristics of these low-copy-number T7 expression vectors should prove very useful for the cloning and high-level overexpression of genes whose gene products are deleterious to the E. coli host. PMID- 7988889 TI - Selective growth inhibition of Porphyromonas gingivalis by bestatin. AB - Recent work in our laboratory indicates that selected protease/peptidase inhibitors interfere with the growth of Porphyromonas gingivalis. The aim of the present study was to further investigate the inhibitory effect of bestatin on the growth of P. gingivalis. Complete growth inhibition of P. gingivalis (11 strains) was observed when bestatin was incorporated at 2.5 micrograms ml-1 in a complex broth medium. Fifty percent inhibition was still obtained with bestatin at a final concentration of 0.5 microgram ml-1. The inhibitory effect of bestatin was highly specific as the growth of 20 different oral bacterial species, including Gram-positive and Gram-negative as well as saccharolytic and asaccharoltic bacteria, was not affected even at bestatin concentrations up to 50 micrograms ml 1. Bestatin did not significantly affect the viability of P. gingivalis indicating that it has a bacteriostatic rather than a bactericidal effect. Growth assays using other specific inhibitors suggested that the effect of bestatin on the growth of P. gingivalis was unlikely to be related to its aminopeptidase inhibitor activity. Cultivation of P. gingivalis with a subinhibitory concentration of bestatin did not modify the cell envelope protein profile, as determined by SDS-PAGE analysis, but significantly decreased the number of extracellular vesicles produced. The present study indicated that bestatin is a highly effective inhibitor of cell growth of P. gingivalis. Additional studies will indicate whether bestatin should be considered as a potential drug in the control of P. gingivalis, a suspected pathogen in adult chronic periodontitis. PMID- 7988891 TI - Alternative strategies of 2-deoxyglucose resistance and low affinity glucose transport in the ruminal bacteria, Streptococcus bovis and Selenomonas ruminantium. AB - Streptococcus bovis and Selenomonas ruminantium grew in the presence of the glucose analog, 2-deoxyglucose (2-DG), but the cells no longer had high affinity glucose transport. In S. bovis, 2-DG resistance was correlated with a decrease in phosphoenolpyruvate (PEP)-dependent glucose phosphotransferase (PTS) activity. The 2-DG-selected S. bovis cells relied solely upon a low affinity, facilitated diffusion mechanism of glucose transport and a 2-DG-resistant glucokinase (ATP dependent). The glucokinase activity of S. ruminantium was competitively inhibited by 2-DG, and the 2-DG selected cells continued to use PEP-dependent PTS as a mechanism of glucose transport. In this latter case, the 2-DG selected cells switched from a mannosephosphotransferase (enzyme II) that phosphorylated glucose, mannose, and 2-DG, but not alpha-methylglucose to a glucosephosphotransferase (enzyme II) that phosphorylated glucose and alpha methylglucoside but not 2-DG or mannose. The glucosephosphotransferase (enzyme II) had a very low affinity for glucose and the transport kinetics were similar to the facilitated diffusion system of S. bovis. PMID- 7988890 TI - Identification by Tn10 transposon mutagenesis of host factors involved in the biosynthesis of K99 fimbriae of Escherichia coli: effect of LPS core mutations. AB - Tn10 transposon mutagenesis of Escherichia coli producing K99 fimbriae was carried out to identify host factors involved in regulation of biosynthesis of fimbriae. Two chromosomal mutants were obtained that showed a strongly reduced cell surface expression of K99 fimbriae upon colony blotting and ELISA. Analysis by inversed PCR and nucleotide sequencing showed that one mutant (EP14) contained the Tn10 transposon in rfaQ, affecting the expression of the rfaQGP gene cluster, whereas the other mutant (EP35) was affected in a, to date, unknown region of the genome. Immunoblotting analysis confirmed a Rd1 type of LPS of mutant strain EP14. These findings for the first time indicated an effect of LPS core biosynthesis on the biogenesis of fimbriae at the cell surface. Preliminary experiments indicated that K99 major subunits, in contrast to K88 subunits, strongly bind LPS molecules. PMID- 7988892 TI - Transformation of tetrachloroethylene to trichloroethylene by homoacetogenic bacteria. AB - Eight homoacetogenic strains of the genera Acetobacterium, Clostridium and Sporomusa were tested for their ability to dechlorinate tetrachloroethylene (perchloroethene, PCE). Of the organisms tested only Sporomusa ovata was able to reductively dechlorinate PCE with methanol as an electron donor. Resting cells of S. ovata reductively dechlorinated PCE at a rate of 9.8 nmol h-1 (mg protein)-1 to trichloroethylene (TCE) as the sole product. The dechlorination activity depended on concomitant acetogenesis from methanol and CO2. Cell-free extracts of S. ovata, Clostridium formicoaceticum, Acetobacterium woodii, and the methanogenic bacterium Methanolobus tindarius transformed PCE to TCE with Ti(III) or carbon monoxide as electron donors. Corrinoids were shown in S. ovata to be involved in the dechlorination reaction of PCE to TCE as evident from the reversible inhibition with propyl iodide. Rates of dechlorination followed a pseudo-first-order kinetic. PMID- 7988893 TI - Characterisation of IS1126 from Porphyromonas gingivalis W83: a new member of the IS4 family of insertion sequence elements. AB - The nucleotide sequence of IS1126, the only insertion sequence so far isolated from the oral pathogen Porphyromonas gingivalis, has been determined. It had a nucleotide sequence of 1338 base pair (bp) flanked by 12 bp perfect inverted repeats and generated a 5 bp target site duplication. The single major open reading frame encoded a predicted protein of 361 amino acids and molecular mass of 41 kDa. The gene encoding the transposase was subcloned into pUC18 and the transposase expressed in Escherichia coli minicells. The predicted amino acid sequence of the transposase had homology to putative transposases of IS1106 and IS1186 both of which belong to the IS5 group within the IS4 super-family of insertion elements. On the basis of this homology we propose that IS1126 should also be included in the IS5 group. Southern-blot analysis of a number of P. gingivalis strains using IS1126 as a probe revealed a unique pattern of hybridisation for each strain and the absence of IS1126 from other closely related Porphyromonas species. This should allow IS1126 to be used as a rapid epidemiological tool in studying oral infections by P. gingivalis. PMID- 7988895 TI - Physiological studies on the effect of Ca2+ on the duration of the lag phase of Saccharomyces cerevisiae. AB - Cell multiplication and growth of Saccharomyces cerevisiae were followed in 2-ml test tubes containing Wickerham's synthetic medium or very dilute synthetic media supplemented in various ways. The ability of the cell cultures to leave the lag phase and enter the exponential phase of growth was investigated. Multiplication was assessed by microscopical observation. The results showed great differences in times required for the cultures to leave the lag phases and begin multiplication. In Wickerham's medium, all cultures grew well 6 h after inoculation. In the dilute medium, several days elapsed before all the cultures grew. These cultures went into exponential growth with approximately first order kinetics. In the unsupplemented medium, the 'half-lives' in the lag phase were about 28 h. Addition of either Ca2+ or Ca2+ plus A23187 (calcimycin) reduced the half-lives to 10 and 6 h, respectively. The doubling times in the exponential phases of growth were not shortened by these additions. We suggest that Ca2+ plays a crucial role as a signal to switch on the mode of cell proliferation in S. cerevisiae. PMID- 7988894 TI - Two mutant alleles of mukB, a gene essential for chromosome partition in Escherichia coli. AB - The MukB protein is essential for chromosome partitioning in Escherichia coli and consists of 1484 amino acid residues (170 kDa). We have determined the base changes at the mutated sites of the mukB106 mutant and a newly isolated mutant, mukB33. These mutant mukB genes were each found to carry a single base-pair transition which leads to an amino acid substitution; a serine residue at position 33 was changed to phenylalanine in the case of mukB106, and an aspartic acid residue at position 1201 was changed to asparagine in the case of mukB33. PMID- 7988896 TI - Susceptibility of various purple and green sulfur bacteria to different antimicrobial agents. AB - Several purple and green sulfur bacteria (genera Chromatium, Thiocapsa and Chlorobium) were tested for their sensitivity to different antimicrobial agents by a disc diffusion assay, using thioacetamide as a source of hydrogen sulfide for plate growth. Chlorobium limicola strains were more sensitive to amoxicillin, erythromycin and nalidixic acid, whereas gentamicin and netilmicin were more active against the purple bacteria tested. None of the organisms were sensitive to oxacillin and trimethoprim+sulfamethoxazole. The critical concentrations at the edge of the inhibition zone were also calculated for three organisms and the antimicrobials colistin, mitomycin C, penicillin G, rifampicin, and streptomycin. The results obtained suggest that colistin, mitomycin C, penicillin G would provide selective conditions against the growth of Chlorobium limicola strains, while streptomycin and other aminoglycoside antibiotics would select against purple bacteria. PMID- 7988898 TI - Heterologous expression of the cytochrome P450cam hydroxylase operon and the repressor gene of Pseudomonas putida in Escherichia coli. AB - The cytochrome P450cam hydroxylase operon (camDCAB) of Pseudomonas putida is negatively regulated by a repressor, CamR, which also represses its own gene. The expression in P. putida of both camR and camDCAB is derepressed in the presence of D-camphor. We examined the expression in Escherichia coli of camR and camDCAB by monitoring the enzyme activity of the camD gene product. In the presence or absence of D-camphor in the cell culture, the expression in E. coli of camD was significant and constitutive, suggesting no expression of camR. This lack of expression was confirmed by monitoring the beta-galactosidase activity of camR lacZ translational fusions. However, S1 nuclease mapping revealed that synthesis of camR mRNA in E. coli was significant and constitutive, as observed in the case of camDCAB mRNA. Thus, it is likely that the expression of camR in E. coli is limited at the translational level. PMID- 7988897 TI - Sulfonate-sulfur utilization involves a portion of the assimilatory sulfate reduction pathway in Escherichia coli. AB - Strains of Escherichia coli lacking serine transacetylase or a positive regulator (Cys B protein) of the assimilatory sulfate reduction (ASR) pathway were unable to assimilate sulfonate-S, while single mutants in O-acetyl-L-serine sulfhydrylase (either 'A' or 'B') were able to do so. Mutants unable to reduce sulfate to sulfite were nonetheless able to form and accumulate sulfide and then cysteine from sulfonates, while strains lacking sulfite reductase were not. Thus terminal portions of the ASR pathway are involved in reduction of sulfonate-S to that of cysteine. E. coli K-12 formed cysteine more slowly, and accumulated lesser amounts of it with sulfonate-sulfur than it did from either sulfate or sulfite. These observations are consistent with our earlier report that sulfate is the preferred sulfur source when present simultaneously with a sulfonate. PMID- 7988899 TI - Molecular cloning and sequence analysis of the proBA operon from an extremely thermophilic eubacterium Thermus thermophilus. AB - A 3.6 kb DNA fragment carrying the Thermus thermophilus proBA region, which encodes the first two steps in the proline biosynthetic pathway, was cloned from the Thermus thermophilus gene library, and its complete nucleotide sequence was determined. The deduced amino acid sequence of gamma-glutamyl kinase (40,657 Da), the product of proB gene, and gamma-glutamyl phosphate reductase (48,747 Da), the product of proA gene, showed 44.1% and 44.4% identity to those of Escherichia coli, respectively. The termination codon of the proB gene and the initiation codon of the proA gene overlapped by 2 bp. A possible transcriptional termination structure was found downstream of the proA gene but not downstream of the proB gene. These results indicate that the proBA genes of T. thermophilus form a single operon as in E. coli. PMID- 7988900 TI - Genetic evidence that hepA gene is involved in the normal deposition of the envelope of both heterocysts and akinetes in Anabaena variabilis ATCC 29413. AB - The hepA gene in Anabaena sp. strain PCC 7120 is required for normal formation of the polysaccharide layer of the heterocyst envelope. A plasmid bearing hepA, interrupted by a neomycin-resistance cassette, was transferred by conjugation to wild type Anabaena variabilis ATCC 29413, so that the interrupted hepA gene replaced a homologous sequence. In the recombinant exconjugants, the envelopes of akinetes as well as of heterocysts were altered. PMID- 7988901 TI - Production of hydrolytic enzymes by oral isolates of Eikenella corrodens. AB - Eikenella corrodens isolates from periodontally healthy subjects and adult periodontitis patients were compared for their ability to produce a range of potential virulence factors. All were positive for proline aminopeptidase, thiol dependent haemolysin and esterase activities. Low or negative activities were found against casein, phospholipid, lipid, collagen, aminophosphate, phosphate under acid or alkaline conditions, and eleven other amino acid substrates tested. In oral infections, the haemolytic activity of E. corrodens could be amplified in the reduced environment of the periodontal pocket and damage host cells. Proline aminopeptidase may act against proline residues in collagen, immunoglobulins and complement proteins. PMID- 7988902 TI - Cloning and DNA sequence analysis of bmpC, a gene encoding a potential membrane lipoprotein of Borrelia burgdorferi. AB - Immunoscreening of a lambda gt11 genomic library of Borrelia burgdorferi expressed in Escherichia coli permitted detection of a clone containing a partial sequence of a B. burgdorferi gene encoding a protein with significant homology to TmpC of Treponema pallidum. Subsequent cloning and DNA sequence analysis revealed an open reading frame encoding a protein with 353 amino acid residues. The open reading frame is preceded by putative promoter sequences and a ribosome binding site, and is initiated with a TTG. The putative protein shares 26% identity with TmpC, contains a signal peptidase II sequence, and is also homologous to the gene products of the recently described bmpA and bmpB of B. burgdorferi. This gene has been designated bmpC. Additional sequencing and restriction analysis indicate that it is located at approximately 400 kbp on the chromosomal map of B. burgdorferi, immediately upstream of bmpA and bmpB. PMID- 7988903 TI - Characterization of an Aspergillus nidulans L-arabitol dehydrogenase mutant. AB - The degradation pathway for L-arabinose, which consists of a sequence of alternating reduction and oxidation reactions prior to ultimate phosphorylation, was studied in Aspergillus nidulans wild-type as well as in an L-arabinose non utilizing mutant. The inability of the mutant to use L-arabinose was caused by the absence of L-arabitol dehydrogenase activity. The effect of the mutation on polyol accumulation patterns was studied upon growth on various carbon sources. The presence of L-arabinose resulted in intracellular accumulation of arabitol in this mutant. Moreover, the mutant secreted arabitol under these conditions and, in contrast to the wild-type, featured enhanced expression of enzymes involved in L-arabinose catabolism as well as of extracellular glycosyl hydrolases involved in degradation of the plant cell wall polysaccharide L-arabinan. PMID- 7988906 TI - New insights into the genetic instability of streptomyces. AB - The high level of genetic instability in Streptomyces ambofaciens is related to large scale DNA rearrangements (deletions and DNA amplifications) which occur within a 2 Mb chromosomal region. The genome of several Streptomyces species is linear and the unstable region is present at the chromosomal extremities. This has raised the questions of the role of the unstable region (which is dispensable under laboratory conditions), the functions of the genes present in this area, and the relationships between instability and chromosomal linearity. The unstable region of Streptomyces and the replication termini of several other microorganisms, including Escherichia coli, share numerous common traits. This suggests that the unstable region of Streptomyces includes the replication terminus, and that chromosomal instability is related to the termination process. PMID- 7988905 TI - Cloning, sequencing and expression in Escherichia coli of the low-affinity penicillin binding protein of Enterococcus faecalis. AB - Low-affinity penicillin binding proteins are particular membrane proteins, in several Gram-positive bacteria, which are involved in beta-lactam antibiotic resistance. The structural gene for the low-affinity penicillin binding protein 5 (PBP5) of Enterococcus faecalis was cloned and sequenced. From the sequence of the 3378 bp, a 2040 bp coding region was identified. From biochemical analysis it emerges that E. faecalis PBP5 is a type II membrane protein with an uncleaved N terminal and is composed of 679 amino acids with a molecular weight of 74055. This protein showed 48 and 33% of identity with Enterococcus hirae PBP5 and Staphylococcus aureus PBP2a, both low-affinity PBPs involved in beta-lactam resistance. Anti-PBP5 antibodies cross-reacted with a membrane protein present in other species of enterococci, but the entire gene fragment cloned hybridized only with DNAs of E. faecalis strains, thus suggesting that genes coding for low affinity PBPs of enterococci are not strictly homologous. In this experiment digoxigenin-labelled E. faecalis DNA was used. PMID- 7988904 TI - nif gene expression in a Nif+, Fix- Bradyrhizobium japonicum variant. AB - Bradyrhizobium japonicum USDA 110 has been shown to contain several genetically similar, naturally occurring colony morphology variants. One of these variants, L2-110, although devoid of symbiotic nitrogen fixation, retains significant levels of ex planta nitrogen fixation ability relative to other symbiotically competent USDA 110 variants (MN-110 and I-110). Interestingly, Northern blot analyses revealed that L2-110 nodules, despite their lack of symbiotic nitrogen fixation, contained 65% the level of mRNA for dinitrogenase (nif DK) and 64% the level of dinitrogenase reductase (nif H) mRNA relative to MN-110 nodules. Western blot analyses of tissue from the same nodules detected 32% the level of dinitrogenase and 31% the level of dinitrogenase reductase in L2-110 relative to MN-110. L2-110 appears to be a new class of mutant based on the complete absence of symbiotic nitrogen fixation (Fix-) and the presence of significant ex planta nitrogen fixation (Nif+). PMID- 7988907 TI - Spongiform encephalopathies and prions: an overview of pathology and disease mechanisms. AB - The etiology of spongiform encephalopathies has been sharply contested for decades. At the heart of the issue is the question of disease origin: Are prion disease representative of primary neurodegenerative genetic disorders, or are they bona fide infectious diseases? This article provides a brief outline of the progress made in the elucidation of prion disease mechanisms in the context of pathological support of the 'protein only' hypothesis. The answer to the above question appears to be that spongiform encephalopathies are uniquely both infectious and genetic neurodegenerative diseases. PMID- 7988909 TI - Cloning and sequencing of the pheU gene for tRNA(Phe) of Thermus thermophilus HB8, and genomic mapping of the pheU and pheST genes. AB - The gene pheU for tRNA(Phe) from the extreme thermophile Thermus thermophilus HB8 was cloned and sequenced. It differed from the published tRNA(Phe) sequence by one nucleotide. Both the pheU gene and the pheST genes encoding the alpha and beta subunits of phenylalanyl-tRNA synthetase were located on the physical map of the T. thermophilus chromosome, where pheU was present on a hitherto unrecognized HpaI DNA fragment. PMID- 7988908 TI - Membrane lipids of Mycoplasma fermentans. AB - Membranes of Mycoplasma fermentans, incognitus strain, were isolated by a combination of osmotic lysis and sonication. Analysis of membrane lipids revealed, in addition to free and esterified cholesterol, six major polar lipids dominated by a de novo synthesized compound (compound X), which accounts for 64% of the total lipid phosphorus. Compound X was labeled by palmitate, but not by oleate. Mass spectrometry and gas liquid chromatography analyses of compound X revealed two molecular species with molecular masses of 1048 and 1076 representing, a dipalmitoyl- and a stearoyl-palmitoyl glycerodiphosphatidylcholine. Compound X has the ability to stimulate human monocytes to secret TNF alpha and to enhance the fusion of small unilamellar vesicles with MOLT-3 lymphocytes. PMID- 7988910 TI - Membrane proteins with molecular masses of 88, 90 and 150 kDa are responsible for binding of human immunoglobulin G Fc fragment to the native cells of Mycoplasma salivarium. AB - Mycoplasma salivarium cells bound the Fc fragment of human immunoglobulin G. The activity was remarkably enhanced by Mn2+, but not by Mg2+ and Ca2+; significantly inhibited by D-mannose; and reduced by pronase treatment of the cells. About 90% of the cells treated with pronase were not disrupted. Sodium dodecyl sulfate polyacrylamide gel electrophoresis of proteins of the cells treated with pronase indicated that proteins with molecular masses of 88, 90 and 150 kDa (88 kp, 90 kp and 150 kp) were specifically digested. The results presented suggest that 88 kp, 90 kp and 150 kp, located in the outer surface of the cell membrane, are responsible for the activity of the M. salivarium cells and interact with a carbohydrate-containing moiety (D-mannose) of the Fc fragment in a Mn(2+) dependent manner. PMID- 7988911 TI - Expression of outer membrane proteins by Salmonella enteritidis relating to pH. AB - The pH of the environment influenced the expression of outer membrane proteins by S. enteritidis PT4 growing in broth. Growth in broth at pH 5 to 7 resulted in variation in expression of outer membrane proteins of 18 to 22 kDa. Bacteria became acid-fixed and non-viable following prolonged incubation in broth with a pH below 5, and expression of flagella was repressed. PMID- 7988912 TI - Relationship between infectivity and OspC expression in Lyme disease Borrelia. AB - Borrelia burgdorferi sensu stricto strain 297 and B. garinii strains HP1 and 12 92 were serially subcultured for 36-50 passages in vitro for 1 year. All low passage strains showed abundant expression of outer surface protein C (OspC) in the 22-23-kDa range, but the high-passage strains lost or showed reduced expression of OspC in comparison with the low-passage strains. The low-passage strains efficiently infected outbred ddY mice when inoculated into the hind footpad or peritoneal cavity. In contrast, the incidence of infection with the high-passage strains was low. Isolates from the bladders of mice inoculated with the high-passage strains expressed large amounts of OspC in comparison with those originally inoculated. These results indicate that OspC expression is related to the infectivity of Lyme disease borreliae. PMID- 7988914 TI - Fluoride inhibits the glucan-binding lectin of Streptococcus sobrinus. AB - The glucan-binding lectins of Streptococcus cricetus AHT and Streptococcus sobrinus 6715 were reversibly inhibited by sodium fluoride. Fluoride was superior to chloride, bromide, iodide and thiocyanate in preventing glucan-mediated aggregation of the bacteria. Fluoride was also an effective inhibitor of the sucrose-dependent adhesion of S. sobrinus to glass surfaces. The inhibition of glucan-binding lectin activities may be one of the mechanisms of action of fluoride in preventing dental disease. PMID- 7988915 TI - Corynebacterium glutamicum DNA is subjected to methylation-restriction in Escherichia coli. AB - Efficient electroporation of Escherichia coli with plasmid DNA isolated from Corynebacterium glutamicum depends on the use of Mcr-deficient E. coli strains. The transformation frequency increased nearly 800-fold when the Mcr-deficient E. coli DH5 alpha MCR was used instead of E. coli DH5 alpha. We used E. coli strains with different mutations in the methyl-specific restriction systems to show that McrBC-deficiency is sufficient to generate this effect. The results imply that C. glutamicum DNA contains methylcytosine in specific sequences recognized by the E. coli McrBC system. PMID- 7988913 TI - A simple method for differentiation of Propionibacterium acnes and Propionibacterium propionicum. AB - TLC glycolipid profiles of several culture collection and clinical strains of Propionibacterium acnes and Propionibacterium propionicum were examined. The former were characterized by weak orcinol-positive minor glycolipids of type g, while the others had mainly strong orcinol-positive major glycolipids of type G. The simple and rapid small scale procedure seemed to be useful for differentiation of these phenotypically similar and genotypically closely related species irrespective of their serotypes. PMID- 7988916 TI - Analysis of a primer-independent GTF-I from Streptococcus salivarius. AB - A glucosyltransferase (GTF) gene, designated gtfL, from Streptococcus salivarius was cloned and expressed in Escherichia coli and its nucleotide sequence determined. The GTF-L enzyme catalysed the synthesis of water-insoluble glucan in a primer-independent manner. The nucleotide sequence and derived amino acid sequence of GTF-L were similar in size and domain structure to previously sequenced glucosyltransferases. However, a 464-bp region of high variability was identified which could be selectively amplified from strains of S. salivarius by the polymerase chain reaction and could therefore form the basis for species identification. No sequence-specific motifs related to the solubility and linkage of the glucan product or its need for a dextran primer could be ascertained. PMID- 7988917 TI - [Doppler evaluation of blood flow in the umbilical artery when confronted with morphologic changes in human placenta of pregnancy complicated by diabetes]. AB - Doppler ultrasound velocimetry in umbilical artery was performed in 23 pregnant women in different classes of the diabetes. Results obtained were compared with the afterbirths' morphology. Strict correlation was found between arteries obliteration in the placenta and vascular resistance in higher classes of the diabetes. Normal structure of the villi with signs of their morphological maturity has basic influence on proper umbilical artery flow maintenance. PMID- 7988919 TI - [Diagnosis and treatment of congenital adrenal hyperplasia in women]. AB - In 32 women with signs of androgenization, menstrual disturbances and distinct elevated values of 17-KS, DHEA, pregnantriole, testosterone and very reduced level of 17-OHCS congenital adrenal hyperplasia was diagnosed which established 12.5% individuals with intersexualism. The method of conservative or/and operative treatment and the prognosis were discussed. PMID- 7988918 TI - [Asymptomatic bacteriuria in pregnant women with insulin-dependent diabetes]. AB - Results of studies of the urinary tract of 43 pregnant women with insulin dependent diabetes have been presented. No clinical symptoms of infection of this system were observed in particular trimesters of pregnancy. It was found that, despite the lack of symptoms of the urinary tract infection, the infection as such did occur-most frequently in the 2nd trimester. The most common bacteria in pregnant women with insulin-dependent diabetes (lasting over 10 years) were Staphylococcus epidermidis and Staphylococcus saprophiticus. PMID- 7988921 TI - [Clinical analysis of patients surgically treated for cancer in the body of the uterus]. AB - 107 patients, aged 40 to 87, after surgical intervention with diagnosis of uterine corpus cancer were clinically examined. 68.1 percent of them were 51 to 70 year old women. 20.5 percent had been never pregnant, and 22.47 been pregnant for one time. In 93.2 percent, corpus cancer was revealed after menopause. Among risk factors, there was observed: diabetes mellitus in 7.4%, hypertension in 35.5%, and obesity in 78% of cases. It was stated interdependence between the depth of uterine infiltration, parametrium metaplastic focuses, adnexa metaplastic focuses, cervix infiltration and decrease of adenocarcinoma maturity. The concord between biopsy and clinical stage I degree was stated in 86 percent of cases. PMID- 7988920 TI - [Isolation and purification of transcortin (cortisol binding globulin--CBG) using two-step chromatography]. AB - The isolation of cortisol and progesterone binding globulin (CBG) from pregnant women serum was performed using affinity and hydrophobic chromatography. The purity and specificity of isolated transcortin was tested by agarose gel electrophoresis using racket and cross immunoelectrophoresis and specific CBG antibodies. High purity and immunoreactivity of the isolated globulin destitute of other proteins contamination, were obtained. PMID- 7988922 TI - [A method for visualization of chromosomes from human sperm and its application]. AB - A cytogenetic technique for analysis of human sperm chromosomes is described in this article. It is based on penetration of hamster oocytes after enzymatic treatment and inhibition of cell division during pronuclei stage. Two different methods of capacitation of sperm, that is necessary for them to penetrate the eggs have been considered. Attention is paid to manipulations and technical difficulties on consecutive steps of realisation of this method. This method is applied mainly in analysis of chromosome segregation in males, that are carriers of chromosome aberrations. The possibility of using this method in other clinical cases and basic research has been presented. PMID- 7988923 TI - [Surgical technique for cesarean section of Eduardo Porro (1842-1902) and its significance for obstetric development. In the 150th anniversary year of the method's creator]. AB - It has passed 150th birth anniversary of a great, Italian Obstetrician Eduardo Porro, author of a cesarean section technique consisted of uterine corpus amputation and suturing of the cervix stump into the abdominal wall incision. Eduardo Porro was born in 1842 in Padwa. In 1876, he became the Head of Obstetrics Department in Pawia, and since 1882, the Head of Midwifery School in Milano. He died on May 25th, 1901. That original cesarean section method was introduced by him in 1876. Its main idea was exsection of the uterus, infected at the time of labor. The operation was also performed because of other reasons, such as: wide uterine ruptures, osteomalation, spacions vaginal cicatrization, and uterine atony. In the second part of the 18th century, maternal mortality following so called, classical cesarean section was nearly 100 percent. Introducing the Porro's operative technique decreased maternal mortality to 58%. This method aroused an interest of cesarean section technique improvement at all. The twilight, of the Porro's operation took place in the 1920s as the new method appeared, elaborated by Adolf Kehrer--uterine lower segment transverse incision. PMID- 7988924 TI - [Actinomycosis of adnexa and urinary bladder]. PMID- 7988925 TI - [A case of pelvic actinomycosis in a woman as a complication of long-term IUD use]. AB - The authors present the subsequent case of pelvic actinomycosis which occurred in woman who was using an intrauterine device for 6 years. Because of diversity of opinion, on the base of literature and own experience we propose the management of IUD users with actinomyces. PMID- 7988926 TI - [Inversion of chromosome 10 in a fetus with osteochondrodysplasia]. AB - The case of thanatophoric dysplasia of the fetus was described. The disease was recognized by ultrasound. Karyotyping was successful after fetal blood sampling under continuous ultrasound guidance. An inversion of chromosome 10 was detected in the affected fetus. The confirmation of the thanatophoric dysplasia was done after termination of the pregnancy. The same inversion was detected in unaffected mother. Prenatal diagnosis was made in the next pregnancy. The result was an unaffected newborn delivered on term. PMID- 7988927 TI - [Jubilee of Senior Polish gynecologist Professor Witold Michalkiewicz]. PMID- 7988928 TI - [Usefulness of transcutaneous measurements of bilirubin in infants with jaundice]. AB - Traditionally, in neonatal jaundice, diagnosis is based on repetitive serum bilirubin measurements. The aim of this study was to analyse clinical usefulness of transcutaneous bilirubinometry as a noninvasive screening test in evaluating neonatal jaundice. The material consisted of 106 full-term infants in which 130 meter readings were performed. A Minolta/Air Shields Jaundice Meter 101 was used. Meter readings were compared with serum bilirubin measurements from these infants (correlation ratio was 0.56). After analysing the clinical data, the conclusion was, that transcutaneous bilirubinometer is a useful instrument for assessing neonatal jaundice for clinical purposes. The bilirubinometer can effectively identify infants whose degree of jaundice the need for serum bilirubin determination and can prevent unnecessary repetitive blood sampling in infants not requiring serum bilirubin determination. PMID- 7988929 TI - [Usefulness of measuring bilirubin levels in cord blood for predicting hyperbilirubinemia in newborns]. AB - Umbilical cord serum bilirubin concentration was studied in 800 healthy full-term newborns as a predictor of subsequent hyperbilirubinemia. If cord bilirubin was under 1 mg% the jaundice occurred in 2.4% newborns, where as 89% of the infants with cord bilirubin above 2.5 mg% became jaundiced. PMID- 7988930 TI - [Thyroid hormone levels during pregnancy, labor and puerperium]. AB - Concentration of thyroxine triiodothyronine and reverse-triiodothyronine in serum blood of 30 pregnant women were estimated, like a longitudinal study from 5 to 41 week of pregnancy. Significant increase of concentration of all hormones was observed. We presented also estimation of iodothyronines in blood serum in labor and non-complicated puerperium. We found increase of T3 concentration immediately after delivery, and decrease of level of all hormones in puerperium. PMID- 7988931 TI - [Analysis of unsuccessful outcomes in a group of pregnancies with diabetes from the intensive care clinic of the Institute of Obstetrics and Gynecology in Poznan during the years 1988-1993]. AB - In the present paper we analysed 416 diabetic pregnant women, treated in the Intensive Care Clinic--Poznan, between 1988-93. We found in this period 8 (1.93%) stillbirth, 6 (1.44%) perinatal deaths and 4 (0.96%) deaths in neonatal period. It was together 18 fetal and neonatal deaths, which gives 4.33 per cent of perinatal and neonatal mortality rate. Four newborns died because of RDS, 2 with congenital anomalies (pulmonary hypoplasia), 3 with heart defects and 1 with oesophagus anomaly. Only 3 diabetic pregnant women of the total 18, were under special care from the I trimester, and almost all been difficult to normalize the glycemia. Only in 6 cases this group glycemia profile was below 100 mg/dl, in other 8 cases this value was above 120 mg/dl. Unsuccessful outcomes mostly occurred in women with long--lasting diabetes and with vascular complications. This study prove, that despite substantial reduction of perinatal mortality rate in children of diabetic mothers, diabetes still is a cause of congenital anomalies, as well as fetal anoxia. Special adverse impact of diabetes on the development of the fetus is observed in long--lasting diabetes and uncontrolled metabolism. PMID- 7988932 TI - [Use of the "color doppler" technique in diagnosing ovulation]. AB - Graafian follicle growth and development and Doppler flow analysis of blood vessels in the wall of the follicle, was analyzed. Twelve patients with primary infertility were observed between days 12 to 15 of the cycle. Analysis of resistance index (RI) and pulsatility index (PI) of the wall vessels was performed. Statistically significant difference in RI and PI indices in preovulatory and post-ovulatory period was observed. PMID- 7988933 TI - [Diagnosis and treatment outcome in patients with grade Ia neoplasms of the uterine cervix]. AB - The material collected from 449 women with cervical cancer Ia was carefully studied (359 women with Ia1, and 90 with Ia2). All the methods and results of treatment were presented. 5-years survival after treatment was obtained in 93% of women. PMID- 7988934 TI - [Evaluation of the influence of some factors for determining the effect of surgical creation of an artificial vagina]. AB - The influence some real factors on positive effect of creating artificial vagina was studied in a group of 37 women aged 13-40 with vaginal agenesis. Determination of the proper operation for vaginal agenesis depends on whether a cervix or functioning endometrium is present. Surgical management, in addition to vaginoplasty, aims to prevent the development pelvic endometriosis preserve the capacity for pregnancy. Two MR studies demonstrated the presence or absence of a normal cervix and functioning endometrium. MR imaging assisted in the classification of the abnormality by noninvasively demonstrating the details of pelvic anatomy and the uterine morphologic characteristics. In the McIndoe operation a space is opened up at the site of the absent vagina and a penile shaped prosthesis draped with a split skin graft is inserted into the space and retained while the cavity epithelialises. PMID- 7988935 TI - [HPV 16 in lymph nodes of the lesser pelvis in women with cervical cancer]. AB - HPV 16 was detected in cancer tissue, blood and pelvic lymph node of cervical cancer patients. The role of these discovery is discusses. PMID- 7988936 TI - [Partial androgen insensitivity syndrome]. AB - There were studied 13 individuals with partial androgen insensitivity syndrome (PAIS) and we observed hypertrophy of clitoris in 92.3%, female pubic hair in 69.2%, complete absence of vagina in 69.2% and normal female development of breasts in 38.5%. In the partial form of AIS more frequent than in the complete form surgery for inguinal hernia, for hypertrophy of clitoris and for artificial vagina was necessary. The discussed form of this male hermaphroditism is caused by rare and untypical mutations in the androgen receptor gene and a differential diagnosis must be performed by exclusion above all the anorchism, Mayer Rokitansky-Kustner syndrome and congenital adrenal hypertrophy. Among all cases of AIS the frequency of PAIS appeared 28.3%. PMID- 7988937 TI - [Partial excision of the anterior uterine wall for placenta accreta]. AB - Rapid accumulation of blood from placental separation site during cesarean delivery for placenta accreta obscures the surgical field and quickly leads to deterioration of the patient's vital signs. In turn, these conditions such as uterine rupture, placenta previa, placenta accreta, increase the risk of hysterectomy, blood transfusions and prolonged hospital stay. We used the following technique in one case of intractable bleeding during cesarean for placenta accreta. Following failure to control the bleeding by suture at the placental separation site via the lower segment cesarean incision, the lower uterine segment with the abnormal adherence of placenta to myometrium, was excised. Our experience suggests that this technique could reduce the use of hysterectomy in cesarean for some cases of placenta accreta. PMID- 7988938 TI - [Conservative treatment of two young women with cancer and precancerous lesions of the endometrium]. AB - Two women with endometrial cancer and precancerous lesion treated with medroxyprogesterone are presented. In both patients outcome of neoplasm is obtained. PMID- 7988939 TI - [Ovarian gonadal tumor and reproduction in women]. AB - Seven young patients with ovarian gonadal tumor treated conservative operation are presented. The attention to clinical and pathological difficulties is drown. The treatment advantage these patients at Gynecologic Institute with pathological department is emphasized. PMID- 7988940 TI - Chronic stress and histological effects on the human central nervous system and other organs. AB - The effects of stress are usually studied in animal models. The organs of 103 subjects who died instantly or very rapidly from gunshot wound were histologically studied. Everyone, within organized criminality, lives under chronic stress. In the hypothalamus a marked depletion of neurosecretive granules of neurons in the supraopticus nucleus, paraventricular nucleus and median eminence was observed, with frequent spreading of these granules along the axons, towards the neurohypophysis. Glial proliferation and frequent chronic perivascular edema were observed in the white substance, as were typical stress lesions in the adrenal gland, a marked depletion of lymphocytes in the splenic follicles, a focal coagulative myocytolysis and the consequent fibrosis in the heart, etc. These findings are the expression of the chronic stress response and of the related psychological state that may also be an aspect of depressive disorders. PMID- 7988941 TI - Sex differences in headache sufferers' responsiveness to painful overdistension of the hand-forearm veins. AB - A short-lasting overdistension of the hand-forearm veins, through the application of the Hand Arm Vein Distension (HAVD) test was carried out on patients suffering from migraine (no. = 102) and females with chronic daily headache (no. = 26): chronic tension-type headache (CTH) and migraine with interparoxysmal headache (MIH). Comparisons were made with a group of healthy controls (no. = 20). The HAVD test induced pain more often in female (65%) than in male migraineurs (14%) and female controls (p < 0.01). No significant difference appeared between male migraineurs and male controls. No significant difference was evidenced between female migraineurs in headache and headache-free periods. Patients with CTH showed less sensitivity to HAVD than those with MIH and migraine (respectively p < 0.01 and p < 0.05) and even a longer latency before the onset of pain. The findings show a stronger extracephalic pain sensitivity in migraineurs than in healthy controls, but sex must be taken into account. The results suggest that pain sensitivity is not correlated with the presence of headache. PMID- 7988942 TI - Bilateral sympathetic skin response following nociceptive stimulation: study in healthy individuals. AB - Bilateral sympathetic skin response (SSR) was evaluated in 25 normal subjects aged (29 +/- 5 years). The stimulation (an electrical pulse train randomly applied to the sural nerve) was equal to 0.5-1.0-1.5 times the nociceptive flexion reflex (RIII) thresholds. This method allowed us to quantify the pain threshold, since a close relationship between the RIII threshold and subjective pain threshold has been described. Decrease in latency, increase in amplitude and duration were observed when increasing intensity of stimulation was used. The right-side stimulation produced significantly shorter latencies and higher amplitudes than the left one. The asymmetry index showed a trend of larger responses on the left hand and shorter latencies on the right hand in males. Females displayed less left-right asymmetry than males. A positive correlation was recognized between RIII threshold and amplitude and duration of SSR. Test retest evaluation in 12 individuals revealed good reproducibility of SSR in terms of latency and duration, while amplitudes showed large variability. The accuracy of SSR response concerning latency and duration was better (range 0.88-0.92) when 1.5 RIII threshold was used, showing that painful stimulation should be used to obtain reliable SSR in clinical practice. PMID- 7988943 TI - Is panic attack a mask of psychogenic seizures?--a comparative analysis of phenomenology of psychogenic seizures and panic attacks. AB - The absence of clear clinical criteria for diagnosing psychogenic seizures and the abundance of vegetative symptoms in their structure raise the question of how to differentiate these states from panic attacks (PA). Clinical symptoms of paroxysm were compared in a group of 32 patients with PA and in a group of 15 patients with psychogenic seizures. It was found that the symptoms classified as panic ones according to DSM-III R criteria are equally observed in both groups. These states are differentiated only by the symptom "fear of dying", observed in 20% of patients with psychogenic seizures and in 90% of patients with PA, and by the number of conversion symptoms (5.9 in patients with psychogenic seizures and 2.2 in patients with PA). It is suggested that in both types of paroxysms panic associated symptoms are not specific and these symptoms only reflect affective distress. The latter is specifically expressed in the form of the symptom "fear of dying" during panic attacks and in the form of conversion symptoms during psychogenic seizures. PMID- 7988944 TI - Idebenone, a new drug in the treatment of cognitive impairment in patients with dementia of the Alzheimer type. AB - Alzheimer's disease (AD) is a central nervous system disorder characterized by the presence of neurofibrillary tangles, neuritic plaques and dystrophic neurones in susceptible areas of the brain. Few options for treatment of AD symptomatology are available. We conducted a multicenter, randomized, double-blind, placebo controlled, parallel trial consisting of a 90 day treatment period followed by a 30 day single blind placebo administration and by an optional long term period of treatment up to a year with idebenone in open fashion. Ninety two patients entered the study and nine of them dropped out before the first control. Treatment with idebenone was found effective on memory, attention, and orientation and in slowing down the natural progressive worsening of the disease. The most common side effects associated with this treatment were insomnia, gastralgia, nausea, and anxiety. However, all adverse effects were of mild intensity and did not require specific therapies. PMID- 7988945 TI - New diagnostic strategies for lupus anticoagulants and antiphospholipid antibodies. AB - Laboratories are currently challenged with the problem of ruling out APA in a patient plasmas. In order to optimize the identification of these antibodies, it is necessary to institute a well-planned approach. Both coagulation assays for the identification of LA and solid phase ELISA assays for the identification of ACA are indicated. In the case of LA, it is often necessary to screen the patient plasma with more than one test system. If two screening tests are negative, no further evaluation for the presence of LA is indicated. However, it is imperative to also perform ACA testing. The literature describing LA and ACA testing is growing exponentially. Several new integrated test systems which seek to simplify the approach to the diagnosis of LA have been introduced. These systems employ one test performed under two different conditions (low and high PL concentration). This approach may prove to be the most cost-efficient way of establishing the diagnosis of LA. PMID- 7988946 TI - Clinical and therapeutic aspects associated to phospholipid binding antibodies (lupus anticoagulant and anticardiolipin antibodies). AB - Antiphospholipid antibodies (APA) comprise a family of immunoglobulins characterized by their pattern of reactivity in a number of laboratory tests. Included in this family are lupus anticoagulant (LA) anticardiolipin antibodies (ACA) and antibodies causing biologic false positive serologic tests for syphilis (BFP-STS). LA and ACA occur in a variety of conditions, including other autoimmunes disorders, infectious diseases, neoplasic disorders, in association with certain drugs and in otherwise healthy individuals. Clinical interest in LA and ACA is increasing. Antiphospholipid antibody syndrome is characterized by a triad of clinical features which include fetal loss, thromboembolic disease and thrombocytopenia. Other clinical manifestations related with APA are livedo reticularis, cutaneous necrosis, hemolytic anemia, heart valve disease, chorea, migraine and obstetric problems as fetal growth retardation, pre-eclampsia, post partum serositis or neonatal thrombosis or catastrophic antiphospholipid syndrome. Therapy is mainly directed against the widespread and diverse manifestations associated with the obstruction of small and large vessels. Long term treatment with oral anticoagulation therapy is advised, even if the venous or arterial occlusion occurred many years previously. In patients with primary antiphospholipid syndrome there is no evidence that the prophylactic administration of steroids or immunosuppression will prevent thromboembolic events. Although the administration of more energetic immunosuppression with cyclophosphamide in pulse form is effective in reducing elevated antibody levels, there is usually a rapid rebound to pretreatment levels shortly after discontinuation of the therapy. A history of recurrent fetal loss requires mandatory treatment during pregnancy. Although the actual prospective risk of pregnancy loss in women with antiphospholipid syndrome and prior pregnancy loss is unknown, it may exceed 60%. Because of this many investigators have treated women with antiphospholipid syndrome with either antiplatelet agents, immunosuppressive agents, or anticoagulants in an attempt to improve pregnancy outcome. Unfortunately, there is no unequivocal proof that any of these therapies are fully efficacious. Despite varying treatment protocols, the live birth rate with treatment was 70%, similar to that reported in the recent randomized clinical trial. Thrombocytopenia and autoimmune hemolytic anemia in patients with APA are treated similarly as patients without APA. Treatment of asymptomatic patients isn't indicated, because only approximately 10-15% of patients with APA developed complications. PMID- 7988947 TI - A prospective epidemiological study on the occurrence of antiphospholipid antibody: the Montpellier Antiphospholipid (MAP) Study. AB - The objective of this study was to determine the prevalence and clinical significance of elevated antiphospholipid antibodies (APA) in a large series of patients admitted to a department of Internal Medicine. At the end of entry phase, 1014 patients were tested (488 males-526 females, mean age: 66.7 years, range 18-97). Seventy-two (7.1%) patients were found APA positive at least once: 44 males and 28 females, mean age 69 years, range 23 to 94. Twenty fulfilled the criteria of Primary Antiphospholipid Antibody Syndrome: 10 patients were referred for deep vein thrombosis, 3 had history of deep vein thrombosis, 1 had both arterial thrombosis and a history of venous thrombosis; 2 had thrombocytopenia; 3 had stroke, 1 had a history of a stroke. One patient had SLE according to ARA classification. The most frequent associated disease was cancer: 14 patients, 9 had evolutive malignant disease, 5 were in clinical remission of neoplasia. Other clinical conditions included chronic and/or acute alcoholic intoxication (n = 8), severe atherosclerosis (n = 4), leg ulcer (n = 4). Insufficient data are available about the evolution, but 7 patients died in the year following diagnosis. Eight patients had fluctuations in APA detection: 2 initially APA positive became negative, 5 initially negative became positive and 1 patient was alternatively positive, negative and positive without steroid treatment. Thus, as expected, APA occur in a variety of clinical disorders. The association with cancer or alcoholic intoxication deserves further investigations. PMID- 7988948 TI - Blood cell lipid asymmetry and antiphospholipid antibodies. PMID- 7988949 TI - Experimental models for antiphospholipid studies. AB - Three types of Experimental Animal Models have been used to investigate APA. 1) Passive transfer of APA to nocive mice. Branch et al injected pregnant Balb/c mice with purified IgG APA from patients with recurrent fetal loss. 2) Active immunization with APA. Backimer et al immunized Balb/c mice with a human monoclonal APA carrying the pathogenic idiotypes. 3) Immunization with beta 2 glycoprotein I (beta 2 GPI) (APA cofactor). Using affinity chromatography, we separated two distinct populations of antibodies. One was specific for beta 2GPI without binding to PL. Another population had a dual specificity for PL and beta 2GPI. PMID- 7988950 TI - Low doses of endotoxin potentiate venous thrombosis in the rabbit. AB - Procoagulant activity of the endothelium and of monocytes was induced by an intravenous administration of a low dose of endotoxin in the rabbit. Venous thrombosis induced by a 45-min stasis of the jugular vein was dramatically increased after the administration of endotoxin. Endotoxin enhanced venous thrombosis in a dose-dependent manner which was the highest after the administration of 1 microgram/kg. This effect increased with time but was optimal when endotoxin was injected 4 h before stasis induction. Leukocytes appear to play a key role in this process since mechlorethamine-induced leukopenia totally inhibited thrombus formation. Hirudin and heparin, administered intravenously 5 min before stasis, were both potent inhibitors of endotoxin-induced venous thrombosis exhibiting ED50 values of 3.8 +/- 1.0 and 2.3 +/- 1.1 microgram/kg, respectively. PMID- 7988952 TI - Role of plasminogen activator inhibitor type 1 in the pathogenesis of coronary artery diseases. AB - Patients with ischaemic heart disease have high levels of plasminogen activator inhibitor type 1 (PAI-1). These levels can constitute an independent thrombotic risk factor. In addition, PAI-1 synthesis is greater in the atherosclerotic vessels than in the normal vessels and this can also constitute an atherogenic risk factor. There is a good correlation between insulinaemia and PAI-1, but it has not been demonstrated that the circulating level of PAI-1 depends exclusively on insulinaemia. The increased levels of PAI-1 correlate with other coronary risk factors, especially hypertriglyceridaemia, but high PAI-1 levels are also found in normolipaemic patients. Vascular synthesis of PAI-1 can be promoted by high levels of circulating lipoprotein a. Finally, an exercise programme can increase the fibrinolytic activity of heart disease patients towards normal. PMID- 7988951 TI - Digital image analysis of platelet-extracellular matrix interactions: studies in von Willebrand disease patients and aspirin-treated donors. AB - We have developed an automated image analysis method which provides en face morphometric evaluation of platelet interactions with coverslips coated with extracellular matrices. This procedure gives also additional information on the intensity of platelet-surface interactions in the same specimens. To standardize the method, anticoagulated human blood was flowed at 800 s-1 during 10 min at 37 degrees C through a parallel perfusion chamber in which extracellular matrix (ECM)-coated coverslips were placed. The sensitivity of the new method was tested in similar studies performed in patients with von Willebrand disease or treated with aspirin (500 mg/day). The extent of platelet deposition on the ECMs was evaluated by both standard and new morphometric procedures. Coverslips were successively embedded in resin and processed for cross-sectional analysis and results were compared with those provided by the new automated procedure. A good correlation was found between results of covered surface obtained by both methods (r = 0.86; p < 0.005). Results from perfusions performed with blood from patients with platelet defects confirmed the correspondence of grey levels in the digitized images with the heights of groups of interacting platelets calculated from cross sections. The new automated method, in only one stage, allows a reliable evaluation of the global interaction of platelets with the ECM and effectively detected qualitative modifications in platelet-platelet interactions in patients with known platelet defects. The method described could be applied to the evaluation of the interactions of platelets with purified components of the subendothelium. PMID- 7988953 TI - Alterations in fibrinolytic and protein C pathways in gynaecological surgery: low molecular weight heparin prophylaxis. AB - Several parameters of fibrinolytic and protein C pathways were evaluated in three groups of patients with high (HR), moderate (MR) and low (LR) postoperative thrombotic risk undergoing major gynaecological surgery. The HR and MR groups were subjected to low molecular weight heparin (LMW) prophylaxis. A significant increase in plasminogen activator inhibitor type 1 (PAI-1) antigen and activity levels was observed in the HR patient group in comparison with the MR and LR groups in the preoperative and early postoperative period. In all the groups studied, the maximum increase in the levels of PAI-1 was seen on day 1 after surgery. However, the D-dimeric levels reached the highest level on day 7. A significant increase in activated protein C:alpha 1 antitrypsin (APC:alpha 1AT) complex levels was observed in the HR group in comparison with the LR group, and a strong decrease in protein C inhibitor in the early postoperative period was detected in all the groups. In spite of heparin prophylaxis, 2 HR patients were diagnosed as deep vein thrombosis (DVT) during the postoperative period. Both patients showed pre-operative levels of PAI-1 antigen or activity and APC:alpha 1AT complexes above the mean + 1 SD of the pre-operative levels in the HR group. In conclusion, in HR patients a hypofibrinolytic and hypercoagulable state was detected in the pre-operative and early postoperative periods. The prophylactic LMW heparin dose used in the present report (20 mg/day x 7) was insufficient to prevent DVT in the HR group. At present our HR patients are given higher doses of LMW heparin (40 mg/day x 7). PMID- 7988954 TI - [Breast reduction with superior pedicle. Follow-up of 150 breast reduction plasties with special reference to subjective assessment by the patients]. AB - We present the results of a follow-up of 150 patients after breast reduction by superior pedicle technique performed within the last five years. Objective results, such as scar formation and reduction mass, are presented as well as important subjective results from the point of view of the patients. Pain, sensitivity of the nippel-areola complex and the rate of breast feeding are demonstrated. Problems in sexual behavior and the influence of breast reduction in daily life are discussed. PMID- 7988956 TI - [Are "Busch fracture", "avulsion fracture of the extensor tendon" or "fracture of the dorsal terminal finger joint" synonyms? Anatomic studies of the insertion of the extensor aponeurosis and significance in hand surgery]. AB - With the help of thick transparent cross-sections of fingers, it has been shown that fibers of the extensor aponeurosis insert distal to the avulsed fragment of the distal phalanx. The consequence for hand surgery is not to expose the fragment through a dorsal incision but through a mid-lateral one. In this way, the distant parts of the aponeurosis distal to the fracture remain intact and there is no break in the continuation of the dorsal extensior plate. PMID- 7988955 TI - [Assessment of central nervous system functional disorders in severely burned patients by auditory evoked brain stem potentials]. AB - The recording of brainstem auditory evoked potentials (BAEP) in severely burned patients can be used for judgement of brainstem function independent of consciousness and CNS-effective drugs. The frequency of central-nervous system complications due to burn injuries is between 7 and 30%. Using BAEP-recordings, we found objective neurophysiological parameters of central-nervous dysfunction in 12 of 25 severely burned patients (48%). Specific BAEP-parameters for burn injuries could not be detected. Specifically, very different time courses of BAEP changes were found. In two patients, who died after severe burn injury, typical neurophysiological patterns of progressive cerebral pressure were observed. The measurement of BAEP is a useful diagnostic tool in detecting central-nervous dysfunction after burn injuries, especially for monitoring in non-cooperative patients. PMID- 7988957 TI - [Clinical anatomy of the interosseous arteries of the forearm]. AB - In recent years, several local flaps have been developed, based on the anterior and posterior interosseous arteries and their anastomoses at the wrist (e.g. posterior interosseous flap, pronator quadratus flap etc.). The anatomy of the arterial network supplying the flap is well established in both clinical and anatomical literature. Most authors agree in the constancy of the anastomoses between the interosseous arteries at the wrist and the absence of major anatomical variations excluding the use of the flap. In the present study, which is based on cadaver dissections of 60 preserved specimens, several gross vascular variations of the interosseous arteries have been found. The most frequent types were an additional anastomosis between the posterior interosseous artery and a perforating branch of the anterior interosseous artery in the middle third of the forearm, which was found in 20%. Ring-formations of the palmar and the dorsal branch of the anterior interosseous artery occurred in 5%. The point of perforation of the interosseous membrane by the dorsal branch of the anterior interosseous artery was found to vary in a larger extent, as described previously. PMID- 7988958 TI - [Dorsal gliding and functional spaces of the metacarpophalangeal transition]. AB - Although the relevance of capillary and gliding spaces of the back of the hand and the finger located dorsal to the extensor aponeurosis in the metacarpo phalangeal region between the layers of the subdermal connective tissue is often emphasized clinically in inflammatory and acute traumatic occurrences, hardly any information has been published concerning the morphology of these spaces. By means of plastic-injection techniques, varying configurations of capillary spaces in the distal region of the dorsum manus of cadavers were found. The deep connective tissue spaces located dorsal to the extensor aponeurosis were shown to have proximal connections to the dorsal tendon sheaths of the carpus, whereas superficial gliding spaces tended to vary in their expanse depending on the subcutaneous and epifascial septa. The deep as well as the superficial capillary gliding spaces are adapted as mobilizing and limiting structures for the movements of the metacarpo-phalangeal joints and the various mechanical stresses of the skin of the back of the hand. A high degree of exactness in the reconstruction of the marginal elements of such functional spaces appears to be of special importance with regard to a total restoration of the functional capability of the metacarpo-phalangeal joint region. PMID- 7988959 TI - [Regeneration of peripheral nerves after interposition of acellular muscle into larger defects]. AB - Peripheral nerve grafting is an established procedure in reconstructive surgery. Nerve grafts, however, are only available to a limited extent and patients are faced with neurologic deficits at the donor areas. Pretreated skeletal muscle has been proposed as an alternative grafting material. In nine adult Sprague-Dawley rats, a 2 cm gap of the sciatic nerve is grafted with a M. gracilis segment which has been pretreated through repeated freezing and thawing. Regeneration is evaluated after six weeks postoperatively. The results are compared to nine conventional nerve grafts. Regeneration was evident in all grafts. Histologically, the muscle grafts revealed a high proportion of connective tissue, a good vascularisation but an inferior degree of myelinisation. Morphometrically, the muscle grafts proved to be inferior according to axon counts and myelinisation. Muscle grafts provide a substrate comparable to peripheral nerves regarding the tubular architecture based on laminin. There are however no viable Schwann cells within these substitutes, which makes them inferior compared to conventional nerve grafts for peripheral nerve repair. These results are discussed with respect to further experiments concerning allogeneic nerve grafting and peripheral nerve preservation. PMID- 7988960 TI - [Second toe transplantation in loss of a long finger. Indications--planning- technique]. AB - Transplantation of the second toe is a routinely employed method in reconstructive hand surgery. Most often it is used for thumb or midhand amputations. Following partial amputations of digits distal to the MP-joints, toe transplantations are less frequently employed. However, function as well as cosmesis of the hand after partial amputation of digits can considerably be improved by toe transplantation. The length of the reconstructed finger is a most important aspect of operative planning which has influence on operative technique as well as functional and aesthetic results. A smooth junction at the base of the transplanted toe should be maintained. This can be achieved by adequate soft tissue reduction and exclusion of the metatarsophalangeal joint. Anastomoses of the subcutaneous venous and plantar as well as dorsal arterial vascular systems are recommended. PMID- 7988961 TI - [Aneurysm of the ulnar artery as etiology of carpal tunnel syndrome: case report and first description]. AB - The case of a patient with carpal tunnel syndrome and simultaneous Raynaud's syndrome caused by an aneurysm of the ulnar artery is described for the first time. Preoperative angiography is recommended in these cases. PMID- 7988962 TI - [Use of a fixation pin for fragment stabilization in hand surgery]. AB - To simplify fixation after reattachment of small bony fragments in hand surgery, a system of fixation pins was developed. Fixation pins consist of a threaded portion of variable length and a cutting tip. The shaft diameter is greater than the thread diameter. This helps to avoid redislocation of small bony fragments. The fixation pins can be used in an open or closed technique. Clinical application includes the reattachment of avulsed fragments, intraarticular fractures of the phalanges and distal radius. The clinical results indicate that the fixation pins may be added to the armamentarium used in hand surgery for reattachment of small bony fragments and intraarticular fractures. PMID- 7988963 TI - [A diagnostic error and its forensic assessment]. PMID- 7988964 TI - Assessment of evidence of human rights violations in Kashmir. AB - From a region with ethnic and political contrasts, recent human rights violations are documented through medical examinations of a small sample of victims and through information given by local medical doctors and lawyers. Within the individual case stories of torture, there was consistency between the history and the clinical and paraclinical data. Furthermore, the sum of the evidence fitted into a general pattern of torture and killing of civilians committed by the Indian Security Force. Cases of rarely documented mutilating torture are presented. Examples of difficulties in the assessment of complicated cases where a complete history could not be obtained are given, together with examples of difficulties and inaccuracies arising from the use of interpreters, who were possibly biased. PMID- 7988965 TI - Systemic and ocular findings in 169 prospectively studied child deaths: retinal hemorrhages usually mean child abuse. AB - The presence and location of ocular hemorrhages were prospectively studied in 169 randomly selected child deaths referred to a medical examiner. Causes of death in the study group included natural diseases and various injuries involving the head, trunk, and asphyxia. Retinal hemorrhages were identified in 70 cases: 62 head injuries, four central nervous system diseases (but not other natural diseases), and four deaths of undetermined cause. The presence of retinal, peripheral retinal, optic nerve sheath, and intrascleral hemorrhages were strongly associated with head injury as compared to other injuries and natural diseases (Yates corrected P-values < 0.001). Among the head-injured with retinal hemorrhages, nine had a history of severe traumatic event (e.g., an unrestrained rear-seat passenger in high-speed collision) and 53 were victims of inflicted injury (e.g. violent shaking). In the absence of a verifiable history of a severe head injury or life-threatening central nervous system disease, retinal and ocular hemorrhages were diagnostic of child abuse. PMID- 7988966 TI - Age estimation by aspartic acid racemization in dentin of deciduous teeth. AB - In forensic dental medicine, one of the most important endeavors is the estimation of age. We have studied the method of age assessment using the D/L ratio of aspartic acid from the dentin. The age of deciduous teeth has been estimated by measuring the racemization reaction of this amino acid. The results of the present study indicated that the measured D/L ratio for the dentin of deciduous teeth was highly correlated with the real age (r = 0.824 - 0.981 (sigma = +/- 0.5 to +/- 1.3). These results indicate that age can be accurately estimated from the dentin of deciduous teeth, as it can when permanent teeth are used, and that the D/L ratio is more highly correlated with age than is the eruption time of permanent teeth. PMID- 7988967 TI - Biochemical diagnosis of the intravital origin of skin wounds. AB - The performance of a spectrophotometric and a spectrofluorimetric method in the determination of histamine and serotonin in skin samples was compared. The spectrophotometric method was found to be superior in terms of reproducibility and sample stability, so it was chosen for subsequent use. An overall 30 rabbits were wounded at different times prior to and after death and the histamine and serotonin concentrations in the wounds were compared to those of control specimens. Vital wounds were found to result in increased concentrations of the amines. The spectrophotometric method was also applied to human skin samples from 12 corpses showing body signs of violence. PMID- 7988969 TI - [Thrombocyte function inhibitors in stroke prevention. Ticlopidine as an alternative to acetylsalicylic acid]. PMID- 7988968 TI - A microsatellite polymorphism in the von Willebrand factor gene: comparison of allele frequencies in different population samples and evaluation for forensic medicine. AB - The allele frequencies at the tetranucleotide repeat (TCTA) vWA locus in the vWF gene were determined in the general Finnish population, in a population representing an internal isolate of Finland, in the Vologda-Russian population, and in US Black population samples. The allele and genotype frequencies from these population samples were compared with each other and with those reported from Spanish and British population samples. Statistically significant differences were demonstrated between most of the different groups (Finns vs. Vologda-Russians, Finns vs. US Blacks, Finns vs. Spanish, Vologda-Russians vs. US Blacks, Vologda-Russians vs. Spanish, US Blacks vs. Spanish and US Blacks vs. British Caucasians), but not between the two Caucasoid population samples from Finland and Great Britain, nor between or within the subpopulation samples from Finland and those from Vologda-Russia. In addition, the vWA marker was evaluated and demonstrated to be reliable for forensic purposes and paternity testing. PMID- 7988970 TI - [Sudden deafness--a form of acute hearing loss]. AB - By idiopathic sudden deafness is meant solely sudden sensory loss of hearing, the pathological-anatomical substrate of which is thought to be acute, vascular endolymphatic hydrops of unknown cause. Sudden deafness always affects one ear only, tinnitus and temporary vertigo may be accompanying symptoms. Sudden loss of hearing reflecting an inner ear involvement of general diseases must be distinguished from sudden deafness as defined above, as also from psychogenic deafness, central-neural deafness during the course of multiple sclerosis, sensory hearing loss in Cogan's disease or syphilis. The same applies to tumours of the inner ear or cerebellopontine angle, which may also present in the form of acute unilateral deafness. Treatment--wherever possible on an inpatient basis--of sudden deafness should be initiated immediately in parallel with a targeted diagnostic workup. PMID- 7988971 TI - [Long term blood pressure monitoring in general practice. 4: Reference values and evaluation]. PMID- 7988972 TI - [The protein C-protein S system: an important anticoagulation factor]. PMID- 7988973 TI - [Drug administration via the endobronchial route. Possibilities of drug administration in emergency medicine]. AB - For cardiopulmonary resuscitation, the endobronchial route represents a good means of administering drugs with a systemic effect, such as adrenaline and atropine, even without a venous line. Via this route, however, higher doses are needed (2.5 times as much as those normally given intravenously). In order to produce a larger surface area within the bronchio-alveolar space and thus speed up absorption, the drugs are diluted in 5-10 ml solvent (isotonic saline solution or distilled water). For endobronchial administration of a drug, various techniques are employed, for example, simply injecting it into the upper end of the (endotracheal) tube, puncture of the tube the use of an application probe introduced into the endobronchial tube, aspiration or venacaval catheter, or the EDGAR tube with an injection needle incorporated within the tube wall. After injection, the diluted medication is distributed into the tiny branches of the bronchial tree by repeated hyperventilation. Despite the need for an adequate alternative to the venous route in the field of cardiopulmonary resuscitation, we still have very few reliable facts about the endobronchial application technique. PMID- 7988974 TI - [Adenosine in the heart: an endogenous protective system]. PMID- 7988975 TI - [Sensible diagnosis in suspected immune deficiency]. AB - Patients reporting a marked proclivity for developing infections often present the care-providing physician with a diagnostic problem. If the available diagnostic possibilities are to be used rationally and with proper understanding, a thorough knowledge of the nature of an immune reaction is essential. The present paper contains a step-by-step scheme that may serve as an aid for the diagnostic approach. In addition to the clinical examination and routine laboratory investigations, simple tests such as Merieux multitest and serum antibody titer serve to orientate the doctor on the patient's immune status. More sophisticated time-consuming and expensive tests, such as flow cytometric analysis of immune cells or functional in vitro investigations permit the identification of immune deficiency syndromes. These tests should, however, be undertaken only when severe immunodeficiency is suspected clinically or the orienting studies make it appear likely. PMID- 7988976 TI - [Solitary metastasis to the head of the pancreas in hypernephroid carcinoma]. AB - Metastatic renal cell carcinoma is a major cause of cancer death. Most metastases occur within the first three months after diagnosis of the primary. Solitary metastases at unusual sites are not untypical, and therefore require particular attention. Pancreatic metastasis in general and from a renal cell carcinoma in particular, represent a rare finding. Within the period between 1986 and 1993, only a single patient with a solitary pancreas metastasis was diagnosed and surgically treated at our hospital. Four years after operation, the patient continued to be tumor- and symptom-free. PMID- 7988977 TI - [Long-term blood pressure monitoring in general practice. 5: Case reports and conclusions]. PMID- 7988978 TI - [Treatment of lower respiratory tract infections including pneumonia. Comparative study with i.vl cefotaxime/oral cefixime versus parenteral cefotaxime]. AB - METHOD: In this open, randomized and controlled multicenter study involving a total of 100 hospitalized patients with infections of the lower respiratory tract, including pneumonia, the efficacy and tolerability of sequential treatment with cefotaxime i.v./cefixime oral were compared with those of exclusively parenteral treatment with cefotaxime. The patients received either 2 x 2 g cefotaxime i.v. over a period of 7 to 10 days, or 2 x 2 g cefotaxime over a period of 48 to 72 hours followed by oral cefixime treatment (1 x 400 mg/day) for a further 5 to 8 days. RESULTS: A total of 94 patients were evaluated for efficacy; in 93.6% of the evaluable patients in each treatment group, either a cure or improvement was obtained. In four patients in the cefotaxime group and five patients treated first with cefotaxime and then with cefixime, adverse reactions were observed. For three of these adverse reactions (diarrhea, nausea, aggravation of an pre-existing genital mycosis) an association with the respective test substance was considered to be at least possible. PMID- 7988979 TI - [6th Congress of the German Society for Biological Psychiatry. 6-8 October 1994, Munich. Abstracts]. PMID- 7988980 TI - Clavicular approach to intraosseous infusion in adults. AB - We attempted a clavicular approach to intraosseous infusion (clavicular IO) as a new procedure in adults, and compared the flow rates of subclavian venous infusion, and clavicular, iliac and tibial IO. Furthermore, we observed enhanced roentgenograms of each IO by contrast media. As a result, clavicular IO indicated 11.9 +/- 0.68 mL/kg/hr (mean +/- SD, n = 29), iliac IO 32.2 +/- 4.48 (n = 21), tibial IO 18.9 +/- 1.28 (n = 15), and subclavian venous infusion 15.2 +/- 1.48 (n = 15). There were no statistically significant differences between subclavian venous infusion and clavicular IO. In roentgenograms, the contrast media entered the inferior vena cava from iliac IO, and via the femoral vein by tibial IO. The superior vena cava was enhanced through the subclavian vein in clavicular IO. No complications such as fractures or transclavicular penetrations by the IO needle occurred. In conclusion, clavicular IO may be an alternative infusion technique to provide the fluids into the subclavian vein in adults. PMID- 7988981 TI - Radiation dosimetry with an electron spin resonance spectrometer. AB - Radiation dosimetry was undertaken using an electron spin resonance (ESR) spectrometer in students' laboratory work. Sugar was used as a dosimeter element and irradiated with both an X-ray generator (34 kVp, 8 mA) and a 60Co sealed source (3.7 MBq). The ESR system detects unpaired electrons created by the ionizing radiation. The lowest detection limit of the absorption dose was 20 Gy. PMID- 7988982 TI - Crossreactivity of anti-cardiolipin antibodies with glycolipids and endothelial cells. AB - To investigate the crossreactivity of anti-cardiolipin antibodies (aCL) with glycolipids and endothelial cells, we used (1) culture supernatants derived from Epstein-Barr virus (EBV)-transformed peripheral lymphocytes of patients with systemic lupus erythematosus (SLE) complicated by antiphospholipid syndrome, and also (2) sera from patients with SLE. The results obtained from culture supernatants demonstrated that aCL crossreacts with myelin-derived acidic glycolipid sulfatide, bacterial endotoxin glycolipid lipid A and human umbilical vein endothelial cells (HUVEC). The results obtained from sera showed a significant correlation between levels of aCL and anti-sulfatide antibody, and between levels of aCL and anti-HUVEC antibody. These findings indicate that aCL can bind to the myelin sheath and HUVEC, which may have implications for the pathogenic potential of aCL for nervous system involvement and thrombotic complications. PMID- 7988983 TI - Melkersson-Rosenthal syndrome: distal facial nerve branch palsies, masseter myopathy and corticosteroid treatment. AB - We described a case of Melkersson-Rosenthal syndrome in whom facial nerve branch palsies and an isolated masseter muscle atrophy were found in association with indolent multifocal facial soft tissue swellings. Non-caseating granuloma was found by the biopsy of swollen upper lip. Facial nerve conduction studies showed extremely low amplitude of compound muscle action potentials with slightly elevated distal latencies. Electromyogram of the atrophic masseter muscle indicated myogenic process. The persistent swellings responded dramatically to a 3 day-course of intravenous methylprednisolone (1,000 mg/day) followed by maintenance oral prednisolone but the facial nerve branch palsies responded rather slowly. Granulomatous involvements of the distal facial nerve branches and consequent wallerian degeneration appear responsible for this type of facial paralysis in Melkersson-Rosenthal syndrome and thus corticosteroid be used for a prolonged period in order to ensure the functional improvement. PMID- 7988984 TI - Henoch-Schonlein purpura associated with pregnancy in a patient with chronic thyroiditis. AB - A case of Henoch-Schonlein purpura with chronic thyroiditis associated with pregnancy is reported. A 27-year-old woman had a struma since age 14. She felt easily fatigable along with enlargement of the struma after the delivery of her first child, and was diagnosed as having chronic thyroiditis. She developed hematuria between the first delivery and the second pregnancy. The hematuria continued during the second pregnancy and in the postpartum period. Immediately after the delivery of her second child, she developed purpura followed by arthralgia and melena. Renal biopsy revealed focal segmental and global type Henoch-Schonlein nephritis. We reviewed five cases of Henoch-Schonlein purpura associated with pregnancy and found that our case is the first in which purpura developed immediately after delivery. Our patient would have developed Henoch Schonlein nephritis between the first delivery and the second pregnancy. She developed Henoch-Schonlein purpura possibly due to rebound activation of immune response in the postpartum period after the disappearance of dramatic suppression of both humoral and cell-mediated immunity in the pregnant period. PMID- 7988985 TI - Reappraisal of preoperative carcinoembryonic antigen levels as a prognostic factor in resectable colorectal cancer. AB - Preoperative carcinoembryonic antigen levels in sera were measured in 124 cases of primary colorectal cancer, and their usefulness as a prognostic factor were evaluated. There were no significant differences in the CEA levels with regard to age, sex, size of the primary tumor, histological differentiation, peritoneal dissemination or DNA ploidy, but CEA levels were significantly higher in patients with liver metastasis. By using Cox proportional hazard model, the most significant discriminant in prognosis was liver metastasis, followed by preoperative CEA level, depth of invasion and DNA ploidy pattern. Preoperative CEA measurements were applied as a parameter of biological behavior of colorectal cancer in the follow-up course. PMID- 7988986 TI - Health system performance in OECD countries, 1980-1992. Organization for Economic Cooperation and Development. AB - U.S. health expenditure levels and rates of increase continue to exceed those of other Western industrialized nations. The pluralistic U.S. health care system has the highest excess health care inflation and opportunity costs of forgone nonhealth consumption and investment when compared with other major industrialized countries. While poor U.S. performance in terms of life expectancy at birth and infant mortality may partially result from social problems, there is little quantifiable evidence of value for money or equity in terms of health system performance. PMID- 7988987 TI - Medical technology in Canada, Germany, and the United States: an update. AB - Major medical technology is internationally mobile and rapidly diffusing. This study compares the proliferation of six complex medical technologies in Canada and Germany with that in the United States, the traditional high-tech leader. The technologies--open-heart surgery, cardiac catheterization, organ transplantation, radiation therapy, extracorporeal shock wave lithotripsy, and magnetic resonance imaging--are more prevalent in the United States, on a per capita basis, than in the other two countries. This was the case five years ago, too. The differences are large in some cases and small in others. Lithotriptors and imagers are growing annually at double-digit rates in all three countries. PMID- 7988988 TI - Costs and price competition in California hospitals, 1980-1990. AB - Critics of health care reform proposals that incorporate managed competition contend that it has never been broadly implemented. However, insurance plans that combine insurance with the provision of care have been widely implemented and have been tested most extensively in California. This DataWatch explores California's experience with health maintenance organizations (HMOs) and preferred provider organizations (PPOs), the introduction of which was followed by overall reductions in hospital costs. These reductions were larger in competitive markets. If implemented on a national scale, such selective contracting could be expected to reduce the growth of hospital costs even more rapidly than occurred in California. PMID- 7988989 TI - Long-term care insurance and Medicaid. AB - Depending on length-of-stay, somewhere between 29 percent and 38 percent of long term care insurance purchasers who use nursing homes would qualify for Medicaid payments if they did not own a policy. This is equivalent to between 13 percent and 17 percent of all policyholders. Owning such a policy would, however, reduce spend-down rates among policyholders by 39 percent. Thus, in the presence of long term care insurance, only 8 to 10 percent of all policyholders would receive Medicaid. Medicaid would spend between $6,492 and $14,179 (in 1990 dollars) on nursing home entrants with long-term care insurance policies--$14,437 to $29,698 if entrants did not have insurance. The ultimate impact on Medicaid expenditures is reduced, however, because many policyholders voluntarily let their policies lapse before entering nursing homes. If policies paid reduced benefits for voluntary lapses, then Medicaid could reap more significant fiscal savings. PMID- 7988990 TI - Medicaid payment for nonphysician practitioners: an access issue. AB - As part of congressional efforts in the 1980s to expand access to care for Medicaid mothers and children, states were required to pay for services provided by certain advanced practice nurses. These mandates created the impetus in many states to expand payment policies for nonphysician practitioners. State Medicaid payment policies are often less restrictive than those of the Medicare program. However, not all states have been receptive to policy expansions and do not cover nonphysician practitioner services to the extent that professional practice acts allow. A few states have yet to meet the 1989 federal mandates. PMID- 7988991 TI - How will outcomes management work? AB - A consortium of employers and managed health care organizations has come together to test the feasibility and usefulness of an outcomes management system, a new strategy for providing information on what types of medical care are effective, for whom, and under what circumstances. Systematic measurement of health outcomes can provide the information that patients, providers, and insurers/employers need to make informed choices among alternative treatments and services. A pilot project in thirteen sites found that outcomes management is feasible for evaluating ongoing care for chronic conditions but is difficult to apply for short-term diagnostic or treatment episodes. Further, successful implementation requires a commitment of substantial organizational resources. PMID- 7988992 TI - School-based conflict resolution: give educators more credit. PMID- 7988993 TI - Unconvincing evidence for condemning school-based conflict resolution programs. PMID- 7988994 TI - Comprehensive approaches to school-based violence prevention. PMID- 7988995 TI - The positive case for school-based violence prevention programs. PMID- 7988996 TI - Managed care: promise and concerns. PMID- 7988997 TI - Health care reform and Grantmakers: survey report. PMID- 7988998 TI - AIDS. Independent foundation grant. PMID- 7988999 TI - Reforms in Minnesota: forging the path. PMID- 7989000 TI - Health care financing reform in New Zealand. PMID- 7989001 TI - Germany's health care system: it's not the American way. PMID- 7989002 TI - Employer mandates: a failed American invention. PMID- 7989003 TI - Hawaii's employer mandate. PMID- 7989004 TI - Health care reform in Florida. PMID- 7989005 TI - Praise for RWJ fellowship. PMID- 7989006 TI - Getting physicians involved in the reform debate. PMID- 7989007 TI - The Employee Health Care Value Survey: round one. AB - In a groundbreaking arrangement, a consortium of large employers--the Xerox, GTE, and Digital Equipment Corporations--launched the Employee Health Care Value Survey during fall 1993. Completed by 24,306 employees, this survey was used to develop comparable methods for assessing corporate health care benefit strategies. It also enabled fair comparisons of thirty-two health plans across the country on more than sixty criteria. Variation in performance among plans was substantial, with managed care plans--particularly prepaid group practices and individual practice associations (IPAs)--recording the most favorable rankings on disenrollment, overall satisfaction, and other measures of "bottom-line performance." Variation in enrollees' health among plans was more modest, with indemnity enrollees posing a somewhat greater illness burden to their plans than enrollees of other plan types. The employers and evaluated health plans are now using the results for multiple purposes, including quality improvement initiatives, employee-based plan performance reports, employee contribution strategies, and health promotion programs. PMID- 7989008 TI - Proposals to control high-cost hospital medical staffs. AB - Several health care reform bills would limit Medicare payments to high-cost medical staffs, that is, physicians in hospitals with a high volume of physician services per admission. In a given year, Medicare's payment to the physicians on each hospital's medical staff could not collectively exceed a limit defined as a certain percentage above the national median. Limits of various forms are used in other parts of the Medicare program. This policy would combine cost containment incentives with a clear organizational structure. In addition, medical staffs could be provided with detailed information on their practice styles. PMID- 7989009 TI - Who spoke for the people? PMID- 7989010 TI - Integrating acute and long-term care. AB - Advocates of health system reform are striving to assure that a valuable new benefit for home- and community-based long-term care is included. Yet in many legislative proposals, a long-term care benefit is kept separate from the rest of the benefit package. Experience from the social health maintenance organization (social HMO) demonstration shows that for the elderly at least, community long term care can be integrated with acute care, at a manageable cost. Acute and chronic disease and disability are experienced concurrently. Moreover, disability is not confined to a small group of permanently disabled persons but affects many other persons for short periods. Integration of long-term and acute care in a managed care model serving a broad population may promote more effective acute care and more efficient and affordable long-term care. PMID- 7989011 TI - Global budgeting in Germany: lessons for the United States. AB - In 1993 Germany implemented significant health reform legislation that, among other things, strengthened the global budgeting of physicians and instituted global budgeting of pharmaceutical expenditures. German physician expenditures are now capped at the growth in income of members of the sickness funds, in contrast to prior years, in which some growth above a targeted level was allowed. For the first time, dental services also are subject to the budget cap. The new reform legislation also limits growth in pharmaceutical expenditures by increasing the level of copayments and by placing physicians as a group at financial risk for growth over the limit. This paper examines the effect of these reforms during the first year and offers lessons for reform of the U.S. system. PMID- 7989012 TI - The value of liability in medical malpractice. AB - In this paper I estimate the strength of medical providers' incentive to avoid negligent medical care, taking account of the facts that many victims of medical malpractice do not file claims, many nonvictims do file claims, legal costs are high, and the legal system makes errors. Despite these problems, the negligence system creates a strong financial incentive for medical providers to avoid substandard care: The average cost of negligence is $135,000 per malpractice claim involving negligence and $3,500 per occurrence of negligent medical care. These substantial penalties suggest that if liability were abolished without adopting effective alternative sanctions for negligent medical care, the number and cost of medically caused injuries and deaths could rise sharply. PMID- 7989013 TI - It ain't necessarily so: the cost implications of health care reform. PMID- 7989014 TI - Health care reform: a reality check. PMID- 7989015 TI - Definitive treatment of patients with serious mental disorders in an emergency service, Part I. PMID- 7989017 TI - Implications of the Health Security Act for mental health services for children and adolescents. AB - Lack of adequate insurance coverage is one reason that the percentage of children who currently utilize mental health services is significantly lower than the estimated percentage of children with serious mental disorders. Principles of a reformed health care system with particular relevance for children's mental health services include coverage of a broad array of home- and community-based services, provision of organized systems of care for children with serious and persistent mental illness, mechanisms to ensure appropriate utilization of services, and provision of mental health services on the same terms and conditions as other health services. The Clinton Administration's proposed Health Security Act embodied many of these principles. In addition, its call for universal coverage and for elimination of insurance exclusions for preexisting conditions would extend mental health coverage to children who are currently uninsured or underinsured; the plan would also expand the range of services covered to include state-of-the-art approaches such as intensive nonresidential services and other alternatives to hospitalization. Implementation of the proposed plan would require developing the service and workforce capacity to provide a full continuum of services, ensuring availability of existing services, integrating existing and new systems of care, guarding against underserving children with serious mental illness, and planning for the role of Medicaid funding in the reformed health care system. PMID- 7989016 TI - President Clinton's proposal for health care reform: key provisions and issues. AB - Shortly after his election in 1992, President Clinton appointed a health care reform task force to develop a proposal for providing health care benefits for all American citizens and legal residents. Between February and May 1993 the Interdepartmental Working Group, composed of more than 30 working groups addressing specific health care issues, prepared options for the task force. The Health Security Act was introduced in November 1993. Besides universal coverage and a basic benefit package, provisions included health insurance reform, regional alliances for structuring competition among health insurance plans, consumer choice of health plans, and provisions for Medicaid beneficiaries. Proposed mental health and substance abuse provisions included coverage of intensive nonresidential services, medical management, evaluation and assessment services, and case management. Initial limitations on coverage of inpatient mental health services and psychotherapy would be removed by 2001. The Clinton plan also called for integration of public mental health and substance abuse services into the full range of health services offered by local health plans. Major issues that will have to be resolved if health care legislation is to be enacted include whether regional alliances should be mandatory and whether employers should be required to contribute to insurance premiums. PMID- 7989018 TI - The Medicaid program and the Clinton plan: implications for mental health services. AB - This paper reviews problems that the Medicaid program poses for health care reformers and how the Clinton plan would deal with them. The Clinton plan represents a compromise between preserving or expanding the Medicaid program and eliminating. The plan would seek to extend services to those without insurance and reduce health care costs, partly by limiting services and increasing out-of pocket costs for Medicaid beneficiaries. All Medicaid beneficiaries would be included in the same basic system of health care that the plan proposes for other Americans. All current beneficiaries would remain eligible for Medicaid, but services would be reduced for many of them. However, services that are important for persons with severe mental illness would be maintained. The plan also would increase out-of-pocket costs for premiums and services, and these increases could be significant for some beneficiaries. PMID- 7989019 TI - Reflections on the mental health community's experience in the health care reform debate. AB - The creation of an effective coalition of mental health organizations was integral to the mental health community's early success in furthering coverage for mental health services in national health care reform. A unified coalition was able to establish political credibility and clarify substantive choices while the Task Force on National Health Care Reform was formulating the Clinton Administration's proposal, leading to initial indications that parity for mental health benefits and flexible coverage of a wide range of services would be included. As concerns about the cost of the benefit package increased, the Administration stepped back from including comprehensive coverage, and some organizations in the coalition became divided over specific provisions. However, as of June 1994, the mental health community's consistent consensus about the need for comprehensive coverage and parity enabled the field to gain inclusion for mental health services and, in fact, wider coverage in some of the proposals emerging from Congressional subcommittees. PMID- 7989020 TI - Integrating mental health into a general health care system. AB - To implement the proposed Clinton mental health benefit for the year 2001 requires a capacity to manage a flexible, comprehensive benefit. If fragmentation of services and discontinuity of care are to be reduced, mechanisms must be developed to coordinate services among domains--between acute and chronic care, and among public and private providers. Evidence exists that basic mental health services generally can be managed in health maintenance organizations (HMOs) with considerable cost savings and without detrimental effects on health, but it is less clear whether this is true of services for persons with severe and persistent mental illness. Effective services for persons with severe disorders require a capacity to organize and manage services across broad medical and social areas, but anticipated costs encourage providers to narrow the scope of care they offer and to select low-risk patients. Much will depend on developing methodologies that allow providers to be reimbursed accurately in relation to risk and that protect small providers from the potential cost of acquiring too many high-risk patients. PMID- 7989021 TI - Health maintenance organizations, health care reform, and persons with serious mental illness. AB - Implementation of the Clinton Administration's proposed Health Security Act could significantly increase the number of seriously mentally ill persons enrolled in health maintenance organizations (HMOs). Studies of the mental health status and outcomes of seriously mentally ill persons treated in HMOs show conflicting findings and provide little guidance about the likely effect of the Health Security Act on this population. However, implementation of the Health Security Act would be likely to influence the treatment of seriously mentally ill persons by altering the activities of state and local governments in the financing and delivery of care, facilitating the integration of public and private services, and encouraging development of additional service capacity. To clarify HMOs' likely role in providing services to seriously mentally ill persons under health care reform, more research is needed on the current service capacity of HMOs, on treatment approaches and outcomes in different HMO models, on whether seriously mentally ill persons would be likely to choose HMOs from among health plan options, and on whether higher-income HMO enrollees would seek care outside HMO provider networks. PMID- 7989022 TI - Who will pay for health reform? Consequences of redistribution of funding for mental health care. AB - Current health care reform proposals will expand coverage and alter the delivery of mental health services. Much of the debate has focused on the cost of coverage rather than on the question "Who will pay?" This paper analyzes the consequences of redistribution of the financial burden of care. The analysis reveals two concerns. First, current employer-based proposals are somewhat regressive because premium costs fall disproportionately on lower-income workers. Second, the increase in federal government subsidies may lead to a significant decline in state and local government financing for mental health services. Both of these concerns have been partly addressed in reform proposals, but there are political barriers to more progressive, non-employer-based approaches and to strategies to retain state and local dollars for mental health services. These distributional issues are critical for a mental health system serving the poor and depending so heavily on state and local resources. PMID- 7989023 TI - Can state mental health agencies survive health care reform? AB - State mental health systems have undergone dramatic changes in the last 40 years, including decreases in state hospital capacity and increases in the proportion of mental health care provided in ambulatory settings and in general hospital units and private psychiatric hospitals. Health care reform is likely to accelerate these changes. The authors consider whether state mental health agencies have a future, given that they were created to operate state hospitals, a role that has been greatly diminished. The authors suggest that state mental health agencies will continue to exist, but that their role will change significantly. PMID- 7989024 TI - Health care reform based on an empowerment model of recovery by people with psychiatric disabilities. AB - People with psychiatric disabilities have articulated a model of recovery that encourages their empowerment by emphasizing consumer-defined goals, liberty, self control of symptoms, peer support, elimination of discrimination, and provision of adequate material and social supports. Application of this model to health care reform requires public education to fight discrimination, an end to the use of involuntary interventions in the name of treatment, further development of services run by survivors-consumers and other alternatives to psychiatric hospitalization, and increased involvement of survivors-consumers in decisions related to their treatment and support. To promote empowerment of people with mental health problems, health care reform should include affordable, universal coverage without exclusions for preexisting high-risk conditions, parity of mental health benefits with other benefits, which includes coverage for voluntary services only, and incentives for funding long-term care, alternatives to hospitalization, and holistic healing services. PMID- 7989025 TI - Coverage of mental health and substance abuse services under a single-payer health care system. AB - Health care reform proposals based on a single-payer system of health care insurance were introduced in the U.S. Congress in 1992 and 1993 but were superseded by the Clinton Administration's health care reform proposal, which was based on managed competition. In a single-payer system, the government collects all health care funding and pays private- and public-sector providers; similar providers are paid the same rate. Other features include consumer choice of providers, distribution of risk of high utilization over the entire nation, and control of health care expenses via an annual national health care budget. Such proposals cover outpatient, inpatient, and long-term care and case management services for mental illness and substance abuse disorders, call for periodic utilization review of continuing mental health care, and eliminate the distinction between public and private services based on limits of coverage. The last provision particularly affects severely or chronically mentally ill persons who are likely to exhaust their private insurance coverage. PMID- 7989026 TI - Treated prevalence rates of severe mental illness among HMO members. AB - OBJECTIVES: The authors examined the extent to which health maintenance organizations (HMOs) enroll and provide services to people with severe mental illness. METHODS: The automated pharmacy system of a large HMO identified members who had received a prescription for an antipsychotic drug or lithium during the two-year study period (1986 and 1987). These data, combined with data from a 2 percent random sample of HMO members and from medical records, were used to identify members who satisfied DSM-III-R criteria for schizophrenia and bipolar disorder. Treated prevalence rates derived from these data were compared with estimated treated prevalence data obtained in the National Institute of Mental Health's Epidemiologic Catchment Area (ECA) survey. RESULTS: Although methodological complications and small sample sizes precluded a detailed comparison, the study found a significantly lower treated prevalence rate of schizophrenia among HMO members than in the ECA survey. The treated prevalence rate of bipolar disorder was also lower than the ECA rate, but the difference was not significant. CONCLUSIONS: The differences in treated prevalence rates seemed to be the result of different study methodologies and factors influencing HMO membership. The results underscore the need for a comprehensive study of the course of severe mental illness among HMO members. PMID- 7989027 TI - Psychiatric hospitalization of adolescents for conduct disorder. AB - OBJECTIVE: The authors' goal was to review current published literature on the psychiatric hospitalization of adolescents with a diagnosis of conduct disorder. METHODS: The English-language literature from 1980 to 1991 cited in the MEDLINE database was searched using the key words conduct disorder, adolescent psychiatric hospitalization, psychiatric hospitalization criteria, adolescent psychiatric inpatient hospitalization, and adolescent psychiatric admissions. RESULTS: A diagnosis of conduct disorder or presenting symptoms and behaviors consistent with that diagnosis are commonly reported for adolescent psychiatric admissions. Estimates of the percentage of admissions to psychiatric inpatient treatment facilities of adolescents with conduct disorder or symptoms consistent with that disorder range from 30 to 70 percent. There are no research-based criteria for hospitalization of adolescents for conduct disorder, and systematic studies of the outcome of psychiatric hospitalization for this group have not been published. Comorbid psychiatric diagnoses and similar behavioral symptoms in conduct disorder and comorbid disorders complicate inpatient treatment of adolescents with conduct disorder. CONCLUSIONS: Studies of the outcome of psychiatric hospitalization of adolescents for conduct disorder are needed to determine the appropriate use of this modality. PMID- 7989028 TI - A quality improvement program in a state hospital during a period of downsizing. PMID- 7989029 TI - Responses of state hospital patients to Hurricane Iniki. PMID- 7989030 TI - Tort liability coverage for community providers who serve insanity acquittees. PMID- 7989031 TI - A brief scale to help identify outpatients' level of need for community support services. PMID- 7989032 TI - Training in psychotherapy. PMID- 7989033 TI - Mammalian meiotic recombination: a reexamination. AB - Recombination nodules (RNs) are small electron-dense structures associated with the synaptonemal complex. Two types have been identified: early RNs present during zygonema-early pachynema, which are thought to be involved in gene conversion and synaptic initiation, and late RNs present during mid-to-late pachynema, which are thought to be involved in reciprocal recombination leading to chiasma formation. In organisms as diverse as Sodaria, Drosophila, and plants there is indeed a close correlation between the observed number of late RNs and crossovers, or their cytogenetic manifestation, chiasmata. However, as this reexamination of the human data shows, there is not a similar correlation in mammals. Instead, there is a severe deficiency in RNs in eutherian males and marsupial females near chromosome ends and other recombinational "hot spots" (defined genetically), or "localized chiasmata" (defined cytogenetically). Many of these sites of hyper-recombination correspond to sites of telomere or telomere associated sequences. Together these observations suggest the possibility of a second, mechanistically different, recombination pathway that does not involve RNs, but may directly involve telomere or telomere-associated sequences. This pathway may be responsible for sex-specific hot-spots of recombination observed at highly localized sites throughout the genome. PMID- 7989034 TI - Determinants of the factor IX mutational spectrum in haemophilia B: an analysis of missense mutations using a multi-domain molecular model of the activated protein. AB - A multi-domain molecular model of factor IXa was constructed by comparative methods. The quaternary structure of the protein was assembled by docking individual domains through consideration of their shape complementarity, polaric properties and the location of cross-reacting material positive/negative (CRM+/-) variants on domain surfaces. Some 217 different missense mutations in the factor IX (F9) gene were then selected for study. Using maximum likelihood analysis, missense mutations affecting highly conserved amino acid residues of factor IX were shown to be 15-20 times more likely to result in haemophilia B than those affecting non-conserved residues. However, about one quarter of this increase in likelihood of clinical observation could be attributed to the magnitude of the amino acid exchange. Missense mutations in structurally conserved residues were found to be 2.1-fold more likely to come to clinical attention than those in structurally variable residues. Missense mutations in residues whose side chains were inwardly pointing were 3.6-fold more likely to be observed than those in surface residues. These observations imply a complex hierarchy of sequence/structure conservation in the protein. The severity of the clinical phenotype correlated with both the extent of the evolutionary sequence conservation of the residue at the site of mutation and the magnitude of the amino acid exchange. Further, the substitution of residues exhibiting minimal side chain solvent accessibility was associated disproportionately with severe haemophilia compared with that of surface residues. Clusters of CRM+ mutations were observed at factor IX-specific residues on the surface of the molecule. These clusters may reflect factor IX-specific docking interactions. The likelihood that a given factor IX mutation will come to clinical attention is therefore a complex function of the sequence characteristics of the F9 gene, the nature of the amino acid substitution, its precise location and immediate environment within the protein molecule, and its resulting effects on the structure and function of the protein. PMID- 7989035 TI - Presence of chromosomal mosaicism in abnormal preimplantation embryos detected by fluorescence in situ hybridisation. AB - The extent of chromosomal mosaicism in human preimplantation embryos was examined using an improved procedure for the preparation and spreading of interphase nuclei for use in fluorescence in situ hybridisation, allowing the analysis of every nucleus within an embryo. One cell showed no hybridisation signals in only three of the 38 embryos that were included in this study, i.e. the hybridisation efficiency per successfully spread nucleus was 99% (197/200). Double-target in situ hybridisation analyses with X- and Y-chromosome-specific probes was performed to analyse nine embryos resulting from normal fertilisation, 22 polypronucleate embryos and seven cleavage-stage embryos where no (apronucleate) or only one pronucleus (monopronucleate) was observed. We also analysed autosomes 1 and 7 by double-target in situ hybridisation in the nuclei of two apronucleate, one monopronucleate and four polypronucleate embryos. All nine embryos that resulted from normal fertilisation were uniformly XY or XX. None of the apronucleate or monopronucleate embryos was haploid: three were diploid, one was triploid and three were mosaic. Fertilisation was detected by the presence of a Y specific signal in four of these embryos. Of the polypronucleate embryos, two were diploid, two were triploid and 18 were mosaic for the sex chromosomes and/or autosomes 1 and 7. These results demonstrate that fertilisation sometimes occurs in monopronucleate embryos and that chromosomal mosaicism can be detected with high efficiency in apronucleate, monopronucleate and polypronucleate human embryos using fluorescence in situ hybridisation. PMID- 7989036 TI - Location of the gene causing hyperimmunoglobulinemia D and periodic fever syndrome differs from that for familial Mediterranean fever. International Hyper IgD Study Group. AB - The hyperimmunoglobulinemia D and periodic fever (hyper-IgD) syndrome is typified by recurrent febrile attacks with abdominal distress, joint involvement (arthralgias/arthritis), headache, skin lesions, and an elevated serum IgD level (> 100 U/ml). This familial disorder has been diagnosed in 56 subjects worldwide. As the hyper-IgD syndrome resembles familial Mediterranean fever, one could speculate that both result from mutations in the same gene. The gene causing familial Mediterranean fever (MEF) has been located on chromosome 16p. We have studied 10 families with 19 affected and 28 non-affected subjects. The clinical findings and IgD determinations from these families are compatible with autosomal recessive inheritance. Using highly polymorphic markers surrounding the MEF gene, only negative Lod scores were obtained, whereas haplotype analysis excluded this locus as the cause of the hyper-IgD syndrome. In addition, no indication for linkage was obtained with markers from other candidate gene regions on chromosomes 17q and 14q. PMID- 7989037 TI - The detection of mitochondrial DNA mutations using single stranded conformation polymorphism (SSCP) analysis and heteroduplex analysis. AB - A number of mitochondrial (mt) point mutations have been associated with inherited disorders. These pathogenic mutations are usually heteroplasmic. Here we describe the identification of three heteroplasmic mtDNA point mutations using the techniques of single stranded conformation polymorphism (SSCP) and heteroduplex analysis. PMID- 7989038 TI - Physical mapping in the region of the Bruton's tyrosine kinase and alpha galactosidase A gene loci in proximal Xq22. AB - We have produced physical maps of the proximal part of Xq22, containing the Bruton's tyrosine kinase (BTK) and alpha-galactosidase A (GLA) gene loci, using long range physical mapping techniques and yeast artificial chromosomes (YACs). These maps reveal five previously unidentified CpG islands which could indicate the presence of other genes in this region. PMID- 7989039 TI - Expression and chromosomal mapping of the gene encoding the human histone H1.1. AB - The expression of a human histone H1 isoform (H1.1) was studied in several human tissues. Northern blot analysis has revealed that this gene is expressed in testis and thymus, but not in other human tissues. In this report, we demonstrate that the expression of the histone H1.1 gene in human testis is restricted to early round spermatids that belong to the fraction of postmeiotic sperm cells. Transcripts hybridizing with the human H1.1 gene could not be detected in testis of mouse, rat, bull or boar. Southern blot analysis with human genomic DNA, DNA from different Old World monkeys (chimpanzee, orangutan, gorilla and rhesus monkey) and DNA from several mammalian species has revealed that the histone H1.1 gene is highly conserved in higher primates, whereas no cross-hybridization can be detected with DNA from other mammalian species such as mouse, rat, hamster or bull. In a previous report, the human histone H1.1 gene and other H1 genes (H1.2 H1.5, H1t) were assigned to chromosome 6 by polymerase chain reaction analysis using human-rodent cell hybrid DNA; fluorescence in situ hybridization indicated that these genes form part of a major gene cluster on the short arm of chromosome 6. We have confirmed the localization of histone H1.1 to chromosome 6 and have regionally assigned the locus to 6p21.3 by radioactive in situ hybridization. PMID- 7989041 TI - Oestrogen receptor (ESR) polymorphisms and breast cancer susceptibility. AB - The allele frequencies of three restriction fragment length polymorphisms at the oestrogen receptor (ESR) locus were compared between breast cancer patients and controls. Leucocyte or tumour DNA from 238 and 122 patients, respectively, and leucocyte DNA from 672 controls was analysed. Alleles having the XbaI restriction site detected by the M72 probe (covering exon 2 and flanking introns) were significantly more frequent in patients than in controls (P = 0.033). Within the breast cancer population, the presence of the XbaI restriction site was associated with late onset of the disease but this association was only of borderline significance. The allele frequencies of the BstUI polymorphism in exon 1 and the PvuII polymorphism in intron 1 did not differ between cases and controls. However, alleles with the PvuII restriction site were more frequent in patients with progesterone receptor negative primary tumours than in patients with progesterone receptor positive primary tumours (P = 0.027). There was no significant association between any of the ESR polymorphisms and the oestrogen receptor status of the primary tumours. The results indicate that the ESR gene or a gene closely linked to it is involved in the development of at least a subset of breast carcinomas. PMID- 7989040 TI - Genetic heterogeneity of severe von Willebrand disease type III in the German population. AB - The genetic heterogeneity of severe von Willebrand disease (vWd) type III was estimated by analysing extended haplotypes of eleven intragenic restriction fragment length polymorphisms and one variable number of tandem repeat polymorphism in 32 patients from 28 families from Germany or of German origin. All patients were screened for gross deletions and for mutations at potential "hot spot" regions of the von Willebrand factor (vWf) gene. Disease-associated haplotypes were established in 24 families. Only a few, apparently unrelated families shared common haplotypes suggesting a considerable genetic heterogeneity in the German population of vWd type III patients. Defects causing vWd type III were identified on 14 out of 56 chromosomes (25%). Gross deletions were detected in two families. A complete homozygous deletion of the vWf gene was displayed in one patient. Another patient was compound heterozygous for a large deletion of at least 100 kb of the vWf gene with an additional, as yet unidentified, defect. One homozygous missense mutation was detected in exon 10, and two nonsense mutations were detected in exon 8 and exon 45 of the vWf gene, respectively. A frameshift mutation (delta C) in exon 18 was identified in five families and an additional frameshift mutation (delta G) was found in exon 28 in one family. It appears that delta C is the most common molecular defect in German patients with vWd type III. Its association with a number of different haplotypes suggests repeated de novo mutations at a mutation "hot spot". Evidence is presented that particular molecular defects causing vWd type III are associated with different patterns of inheritance, depending on their location within the vWf gene. Complete deletions of the gene and nonsense mutations in the pro-sequence are correlated with recessive inheritance, whereas frameshift and nonsense mutations in the gene sequence corresponding to the mature vWf subunit tend to be inherited in a dominant fashion. PMID- 7989042 TI - The motilin gene: subregional localisation, tissue expression, DNA polymorphisms and exclusion as a candidate gene for the HLA-associated immotile cilia syndrome. AB - The product of the human motilin gene (MLN) has an important role in regulating gastrointestinal motility. The precise chromosomal localisation and expression of this gene are still unresolved. Here, we report a detailed study assigning MLN to 6p21.3; MLN is tightly linked to the HLA-DQalpha locus. Moreover, MLN expression has been evaluated in a large series of tissues. Positive signals have been obtained for brain, bronchi and a gastrointestinal malignancy. Direct sequencing exon by exon of the codifying region, intron/exon boundaries and promoter has allowed the identification of three DNA polymorphisms, one of which corresponds to a common protein variant. The chromosomal localisation of MLN, and its expression in broncoepithelial cells suggests that this gene is involved in immotile-cilia syndrome (ICS) disease. Sequence and segregation analysis of the MLN gene carried out in two families, in which the disease locus was previously assigned to 6p21.3, exclude MLN as a candidate gene for the HLA-associated form of ICS. PMID- 7989043 TI - The immunoglobulin heavy chain and disease association: application to pemphigus vulgaris. AB - Genes involved in the immune response are generally encoded from a complex cluster of gene segments. Studies of the association of diseases with such genes require well-defined genetic markers throughout the selected region. A set of 15 polymorphic loci that span 1500 kb of the immunoglobulin heavy chain (IGH) complex, 8 in the variable (VH) region and 7 in the constant (CH) region, were selected for the study of disease association. We present a protocol for the use of multiple immunoglobulin heavy chain (IGH) polymorphisms for general application in disease association studies. No microsatellite repeat markers are available for this region. To demonstrate the applicability of this approach, we have examined these IGH polymorphisms in families with individuals affected with pemphigus vulgaris (PV), an autoimmune dermatologic disease. Allele frequencies in 12 patients with PV were compared with those found in their spouses, and with those in a white Canadian control population. A significant difference was found between PV patients and both control groups for the presence of the VH gene VH3f R4, and possibly for the absence of VH3f-R3, suggesting the possibility of susceptibility factors in these regions. Examination of the frequencies of the IGH region C gamma-haplotypes of PV patients indicated that, while the patients did not differ significantly from their spouses (chi 2 = 1.79), both groups were found to differ significantly from the white Canadian control group (chi 2 = 10.10), emphasizing the importance of matching the ethnic background of controls with that of the patient test group in disease association studies. Unexpectedly, two patients had large deletions of genes in the IGH constant region, which could play a role in the development of PV and require further investigation. PMID- 7989044 TI - New sites of methylcytosine-rich DNA detected on metaphase chromosomes. AB - In situ immunofluorescence detection of antibodies against 5-methylcytosine on metaphase chromosomes prepared by a new procedure allows the display of new 5 methylcytosine-rich sites as compared to previously published methods. In short term culture lymphocytes, the immunofluorescent signals give a recurrent pattern in which four types of binding sites can be distinguished. Type I sites are the secondary constrictions and a few juxtacentromeric regions, type II sites correspond to T-bands. Both types I and II sites emit a strong fluorescence. Type III sites form an R-band pattern and emit a weaker fluorescence. Type IV sites are the short arms of acrocentrics, they emit strong but polymorphic signals. The results obtained from control experiments suggest that the pattern observed is rather the expression of an uneven distribution of 5-methylcytosine-rich sites than a consequence of the various treatments used. In a lymphoblastoid cell line known to have a reduced 5-methylcytosine content, it was possible to demonstrate a heterogeneous hypomethylation among chromosome structures, principally involving type I sites. The method opens the possibility of studying in situ on chromosomes, regional variations of methylation in pathological conditions. PMID- 7989045 TI - Genetic heterogeneity of Crigler-Najjar syndrome type I: a study of 14 cases. AB - Crigler-Najjar syndrome type I (CN-I) is an autosomal recessive condition characterized by severe unconjugated hyperbilirubinemia caused by the lack of bilirubin-UDP-glucuronosyltransferase (B-UGT) activity in the liver. Two B-UGTs are coded for by a gene complex (UGT1) that maps to chromosome 2q37 and that also encodes two phenol-UDP-glucuronosyltransferases. Here, we report eleven mutations (including nine novel mutations) of the B-UGT1 gene in a large series of 14 unrelated CN-I children of various geographic origins: France (seven patients: A401P, Q357X, W335X, A368T, 1223insG, A291V, K426E, K437X); Portugal (two patients: G308E); Tunisia (two patients; Q357R); Turkey (one patient: S381R); italy (two siblings: S381R). Interestingly, 6/14 mutant alleles carried by unrelated probands of French ancestry bore the A401P mutation, indicating a founder effect; this effect is probably also present in Portugal, Turkey, and Tunisia. Since mutations occurred in exons 2-5 shared by all mRNAs species of the gene, a combined deficiency of B-UGT and P-UGT was observed in the liver of five patients in whom these activities were measured. The present study confirms that CN-I is genetically heterogeneous and suggests that different founder effects are involved in Western Europe, the Middle East, and North Africa. PMID- 7989046 TI - Exclusion of the cartilage link protein and the cartilage matrix protein genes as the mutant loci in several heritable chondrodysplasias. AB - The chondrodysplasias are characterised by the abnormal development of articulating joints and bone. Mutations in the COL2A1 and COL10A1 genes, which encode the cartilage collagens type II and type X, have been identified in a variety of inherited chondrodysplasias. However, both genes have also been excluded as the mutant loci in several chondrodysplasia pedigrees, indicating the existence of at least one other chondrodysplasia locus. We report the exclusion of the genes encoding two cartilage-specific proteins, the cartilage link protein and the cartilage matrix protein, in several chondrodysplasia pedigrees in which COL2A1 had previously been excluded as the mutant locus. PMID- 7989047 TI - Male meiotic segregation of gonosomes analysed by two colour FISH in human interphase spermatozoa. AB - Human meiotic segregation of X and Y chromosomes was simultaneously analysed by dual fluorescence in situ hybridization (FISH) on 10,638 interphase spermatozoa from the same donor. A modified method for sperm decondensation ensured access of both X and Y probes to the sperm chromatin and a 99% hybridization efficiency. Expected sex ratios were obtained (49.30% haploidy X and 49.22% haploidy Y). The frequencies of meiotic II non-disjunctions for X and Y chromosomes (0.05%) were similar to those observed in sperm karyotypes after heterospecific fertilization of hamster eggs. In contrast, the frequency of XY bearing cells was significantly higher (0.42%). However, XY cells detected by FISH could either be diploid somatic cells, diploid germinal cells or hyperhaploid XY spermatozoa, the latter resulting from meiotic I non-disjunctions. PMID- 7989048 TI - The human RAD51/RecA homologue gene is not a candidate gene for Bloom's syndrome. AB - The human gene HSRAD51/RecA homologue has been investigated as a possible candidate gene involved in Bloom's syndrome. No mutations were found in the cDNA isolated from three different Bloom's syndrome cell lines, thus excluding the possibility that HSRAD51 is directly involved in the syndrome. Other possible candidates are discussed. PMID- 7989049 TI - Exclusion of linkage with chromosome 21 in families with recurrence of non-Down's atrioventricular canal. PMID- 7989050 TI - A componential model of human interaction with graphs: 1. Linear regression modeling. AB - Task analyses served as the basis for developing the Mixed Arithmetic-Perceptual (MA-P) model, which proposes (1) that people interacting with common graphs to answer common questions apply a set of component processes--searching for indicators, encoding the value of indicators, performing arithmetic operations on the values, making spatial comparisons among the indicators, and responding; and (2) that the type of graph and user's task determine the combination and order of the components applied (i.e., the processing steps). Two experiments investigated the prediction that response time will be linearly related to the number of processing steps according to the MA-P model. Subjects used line graphs, scatter plots, and stacked bar graphs to answer comparison questions and questions requiring arithmetic calculations. A one-parameter version of the model (with equal weights for all components) and a two-parameter version (with different weights for arithmetic and nonarithmetic processes) accounted for 76%-85% of individual subjects' variance in response time and 61%-68% of the variance taken across all subjects. The discussion addresses possible modifications in the MA-P model, alternative models, and design implications from the MA-P model. PMID- 7989051 TI - Effects of speech intelligibility level on concurrent visual task performance. AB - Four experiments were performed to determine if changes in the level of speech intelligibility in an auditory task have an impact on performance in concurrent visual tasks. The auditory task used in each experiment was a memory search task in which subjects memorized a set of words and then decided whether auditorily presented probe items were members of the memorized set. The visual tasks used were an unstable tracking task, a spatial decision-making task, a mathematical reasoning task, and a probability monitoring task. Results showed that performance on the unstable tracking and probability monitoring tasks was unaffected by the level of speech intelligibility on the auditory task, whereas accuracy in the spatial decision-making and mathematical processing tasks was significantly worse at low speech intelligibility levels. The findings are interpreted within the framework of multiple resource theory. PMID- 7989052 TI - Effect of visual impairment on driving. AB - The aim of the study was to determine the effect on driving of restricting vision. This was undertaken by comparing the driving performance of young, normal subjects under conditions of simulated visual impairment with a baseline condition. Visual impairment was simulated using goggles designed to replicate the effects of cataracts, binocular visual field restriction, and monocular vision. All subjects had binocular visual acuity greater than 6/12 when wearing the goggles and thus satisfied the visual requirements for a driver's license. Driving performance was assessed on a closed-road circuit for a series of driving tasks including peripheral awareness, maneuvering, reversing, reaction time, speed estimation, road position, and time to complete the course. Simulated cataract resulted in the greatest detriment to driving performance, followed by binocular visual field restriction. The monocular condition did not significantly affect driving performance for any of the driving tasks assessed. PMID- 7989053 TI - Psychophysical foundations of a model of amplified night vision in target detection tasks. AB - In this article we examine some of the basic psychophysics relevant to amplified night vision devices. These devices produce images that are substantially different from ordinary visual scenes. Distortions in contrast and luminance and the introduction of visual interference and geometrical artifacts contribute to unusual viewing conditions. We carried out experiments to determine the effect of these parameters of the image on a highly controlled visual target detection task simulated on a computer graphics system that closely models a night vision device. Our results indicate that display luminance and geometrical artifacts degrade detection performance only slightly, whereas contrast and visual interference have a substantial degrading effect. PMID- 7989054 TI - Psychophysiological measures of workload during continuous manual performance. AB - Twelve subjects (six female) participated in an experiment designed to separate the effects of perceptual/central and physical demands on psychophysiological measures of peripheral nervous system activity. The difficulty of a single-axis continuous manual tracking task was varied in two ways: order of control was manipulated to vary perceptual/central processing demand, and disturbance amplitude was manipulated to vary physical demand. Physiological measures were sensitive to the imposition of a task and were more sensitive to physical than to perceptual/central demands. A principal components analysis identified five factors (three of them physiological) that accounted for 83.1% of the observed variance. Perceptual/central processing demands specifically affected the component identified with sympathetic cardiovascular control, whereas physical demands were reflected in the component identified with parasympathetic cardiovascular control. This finding suggests that dissociations observed among cardiovascular measures in manual performance tasks are attributable to differential activation of the autonomic control systems. PMID- 7989055 TI - Influencing of warning label signal words on perceived hazard level. AB - This experiment investigated the influence of warnings, signal words, and a signal icon on perceived hazard of consumer products. Under the guise of a marketing research study, 135 people (high school students, college students, and participants from a shopping mall) rated product labels on six dimensions, including how hazardous they perceived the products to be. A total of 16 labels from actual household products were used: 9 carried the experimental conditions, and 7 were filler product labels that never carried a warning. Five conditions presented the signal words NOTE, CAUTION, WARNING, DANGER, and LETHAL together with a brief warning message. In another two conditions, a signal icon (exclamation point surrounded by a triangle) was presented together with the terms DANGER and LETHAL. In the final two conditions, one lacked a signal word but retained the warning message, and the other lacked both the warning message and the signal word. Results showed that the presence of a signal word increased perceived product hazard compared with its absence. Significant differences were noted between extreme terms (e.g., NOTE and DANGER) but not between terms usually recommended in warning design guidelines (e.g., CAUTION and WARNING). The signal icon showed no significant effect on hazard perception. Implications of the results and the value of the methodology for future warnings investigations are discussed. PMID- 7989056 TI - Stop stereotyping. PMID- 7989057 TI - "Hello, my name is...". PMID- 7989058 TI - Scholarly caring in doctoral nursing education: promoting diversity and collaborative mentorship. AB - One of the most significant, yet not fully developed goals of doctoral education is the graduation of scholars who can make a major contribution to the discipline of nursing. There have been many discourses and debates about the essential criteria for quality in doctoral programs that create and promote scholarliness. Scholarliness in nursing includes critical thinking, a connection to practice, a commitment to the discipline's mission, substantive mastery areas, philosophical analyses, rigorous investigations, and a social awareness of the relationship between knowledge development and impact on society. Promoting scholarship necessitates the development of a culture of scholarly caring. Scholarly caring can be developed through promotion of diversity and through collaborative mentorship. Features of collaborative mentorship are negotiated relations, mutual interactions, facilitative strategies, and empowerment. To develop these properties of a scholarly doctoral program, attention must be paid to actions that compromise scholarly quality of programs such as the lack of resources and lowered expectations of students. PMID- 7989059 TI - A model for clinical teaching as a scholarly endeavor. AB - The traditional ways that academia has approached documentation of scholarship are relatively narrow and best fit those disciplines whose practice is research and writing. In professional practice disciplines such as nursing, writing and research are critical, but they are not the only scholarly activities in which faculty are involved. A model resulting from work from the Carnegie Foundation for the Advancement of Teaching offers a broader view of scholarship in which clinical teaching has academic legitimacy. The components of scholarship included in the model are discovery, practice, integration, and teaching. PMID- 7989060 TI - Exclusion of certain groups from clinical research. AB - Recent evidence indicates that certain groups such as women, ethnic minorities, the elderly, and the poor may be underrepresented in clinical research. A review was conducted of 754 approved research protocols from one tertiary care center over a 2-year period (1989, 1990) to examine demographic characteristics of subjects. Most protocols (81.4%) included both men and women; 56.6% included people over age 65. About three-fourths described exclusionary criteria. Exclusions for which a justification was least frequently explicated were for age (44.9%), socioeconomic status (42.9%), and race (38.1%). In nursing protocols, only 26.6% included a justification for age. In this study, the elderly, poor and ethnic minorities were found to be excluded without identifiable justification from research protocols. While such disparities must be corrected, there are certain research design considerations that should be taken into account to assure that research questions are answered in the most efficient manner for the most representative group. PMID- 7989061 TI - Replication strategies for nursing research. AB - Implementing research findings into nursing practice has been seriously hampered by the lack of replication studies. One deterrent to replication is the vague and scant treatment that replication methodology has been given in the nursing literature. Knowledge of different replication strategies will enable researchers to choose the most appropriate approach. Four of the most frequently cited classifications of replication research are compared and a review of replication studies in nursing from 1983 to 1992 is included. PMID- 7989062 TI - Differences in the use of hospital-based outpatient mental health services by the elderly. AB - Visits to hospital outpatient clinics and emergency rooms by patients age 65 and over were studied. Differences were found in the use of mental health services between the oldest old and youngest old. A significant portion of psychiatric and substance abuse disorders was found among the youngest old, while the oldest old made a greater number of visits to emergency rooms. PMID- 7989063 TI - Nurse characteristics and professional autonomy. AB - Relationships between selected demographic characteristics and professional nursing autonomy were examined. Identification of such relationships can strengthen development of the professional nursing role. Usable responses were returned by 542 RNs in a random sample of 2,000 nurses from four states. The Personal Attributes Questionnaire (Spence, Helmreich, & Stapp, 1974) and Nursing Activity Scale (Schutzenhofer, 1987) were used. Significant relationships were noted among autonomy and the following: nursing education, practice setting, clinical specialty, functional role, membership in professional organizations, and gender stereotyped personality traits. PMID- 7989064 TI - Turn-of-the-century nursing perspectives on venereal disease. AB - In the early 1900s, nurses, feminists, and social reformers focused on venereal disease as a symbol of women's powerlessness. Authors in popular literature and nursing journals debated the ethics of the "medical secret," whereby physicians collaborated with their male patients to keep wives uninformed of the risk of infection. The nurses Lavinia Dock and Emma Goldman used the topic of venereal disease as a springboard to discuss their contrasting feminist ideologies. Their writings provide a context for current debates about sexual partner notification for HIV and nurses' role in political activism. PMID- 7989065 TI - Infant relinquishment through adoption. AB - The confidential nature of adoption and the stigma associated with out-of-wedlock pregnancies have limited the number of studies of infant relinquishment. Birthmothers' feelings of loss and grief have not been widely acknowledged. The purpose of this study was to describe the experiences of 12 women who had relinquished their infants for adoption. Data were collected using open-ended questions to describe the experiences. Type of adoption influenced the experience of infant relinquishment. Four themes represented the process of relinquishment. PMID- 7989066 TI - Spirituality among caregivers. AB - The spiritual perspectives of 17 caregiver wives of dementia victims and 23 noncaregiving wives of healthy adults were compared in a pilot study using a convenience sample. Caregiver wives used symbols such as God, and spiritual behaviors such as prayer and forgiveness as coping mechanisms. Caregivers tended to share the problems and joys of living according to their spiritual belief more often than the noncaregiver wives of healthy adults. Caregivers also engaged in private prayer and sought spiritual guidance in making decisions in their everyday life more often. The findings suggest that nursing interventions with churches as a natural network for caregivers may be useful. Prayer, forgiveness, and spiritual reading materials are resources that may be helpful to some caregivers. PMID- 7989067 TI - Clinical decision-making styles of home healthcare nurses. AB - Using grounded theory method, this study of 21 home health nurses describes three clinical decision-making styles: skimming, surveying, and sleuthing. Experienced home health care nurses switch from one style to another when managing varying patient care situations. This study provides a broad view of clinical decision making by integrating the context of nursing practice with the patients' clinical status, nurse-patient interaction, and nurses' knowledge and experience. PMID- 7989068 TI - An American's view of nursing education in Japan. PMID- 7989069 TI - A vulnerability-stress framework for evaluating clinical interventions in schizophrenia. AB - Symptom management and prevention of psychotic relapse are major treatment concerns in schizophrenia. Research shows a relationship between psychotic symptom levels and several intrapersonal, interpersonal, and environmental factors. These determinants are incorporated into an etiologic causal model of psychotic symptoms based on a vulnerability-stress framework. Then a multifaceted intervention model to influence symptom determinants is advanced, and examples of intervention elements are specified. Finally, a research agenda to evaluate the effectiveness of the intervention model is described, and related methodologic issues are considered. PMID- 7989070 TI - Reproductive decision-making in the age of AIDS. AB - The forecast for the HIV epidemic in the United States includes increasing numbers of infected women and children, the latter of whom will be born to infected mothers. As the epidemic progresses, nurses will be more frequently called on to assist women in making difficult reproductive decisions. Using four levels of analysis, this discussion explores current knowledge about reproduction in HIV-infected women and suggests interventions and nursing actions. PMID- 7989071 TI - Thrombolytic therapy for prosthetic cardiac valve thrombosis. AB - During 1992-93 12 patients (5 males, 7 females) with thrombosed prosthetic cardiac valves were treated with streptokinase on 13 occasions (one patient with prosthetic tricuspid valve had two thrombotic episodes). Their age ranged from 14 to 52 years (median 39). Two valves were in aortic position, six in mitral and four in tricuspid position. Eight were Bjork-Shiley prosthesis, three were Medtronic Hall valves and one was a St. Jude Valve. Timing of prosthetic valve thrombosis ranged from 3 months to 12 years after valve replacement surgery. Duration of symptoms due to valve thrombosis ranged from 1-4 months with tricuspid valve thrombosis and 1-14 days with left sided valve thrombosis. Five were in functional class II and four each were in functional class III and class IV. All patients were evaluated by echo Doppler and cine fluoroscopy. Loading dose of streptokinase was 2.5 lakh units in 4 patients and 1 lakh units in 9 patients. Maintenance infusion was at 1000 units/Kg/hour in 11 patients and 1 lakh units/hour in 2 patients. Duration of streptokinase infusion ranged from 3 hr to 38 hr. Thrombolytic therapy was successful (clinical, echo Doppler and fluoroscopy) in 12 out of 13 cases (92%). It was unsuccessful in a patient with valve at tricuspid position in whom infusion had to be stopped after 24 hour due to bleeding gums. One patient developed intracerebral bleed and expired. In conclusion streptokinase therapy is useful for prosthetic cardiac valve thrombosis. PMID- 7989072 TI - Left ventricular function and geometry in juvenile mitral stenosis. AB - The purpose of this study was to investigate possible differences between juvenile and adult variety of mitral stenosis (MS) with regard to left ventricular preload, afterload, contractile function and geometry by two dimensional echocardiography. Thirty six consecutive children and adolescents with MS (Group 1, mean age +/- 1 standard deviation 16 +/- 3 yrs) were compared with an equal number of adults with MS of comparable mitral valve area (Group II, mean age 30 +/- 8 yrs). Patients with juvenile versus adult MS had similar left ventricular ejection fraction (0.57 +/- 0.09 vs 0.57 +/- 0.11, p = not significant (NS)), end-systolic wall stress (64.8 +/- 21 vs 64.3 +/- 25 Kdynes/cm2, p = NS), wall stress to end-systolic volume ratio (2.6 +/- 1.2 vs 2.71 +/- 0.9, p = NS) and mass (77 +/- 19 vs 83 +/- 26 gm/m2 p = NS) but the former had greater end diastolic volume (68 +/- 16 vs 57 +/- 18 ml/m2, p = 0.008) and sphericity index (0.62 +/- 0.19 vs 0.50 +/- 0.19, p = 0.01) and lower mass to volume ratio (1.01 +/- 0.32 vs 1.36 +/- 0.42, p (0.01). Compared to normal controls, adult patients with MS had similar end-diastolic volume (58 +/- 13 vs 57 +/- 18 ml/m2), mass (84 +/- 20 vs 83 +/- 26 gm/m2), mass to volume ratio (1.45 +/- 0.4 vs 1.36 +/- 0.42) but greater wall stress (45.6 +/- 11.7 vs 64.3 +/- 25 Kdynes/cm2, p < 0.001) and lower ejection fraction (0.66 +/- 0.07 vs 0.57 +/- 0.11, p < 0.001). Thus patients with juvenile MS have significantly altered left ventricular geometry and increased preload in response to comparably elevated afterload due to compensatory adaptive process. PMID- 7989073 TI - Aortocameral fistula to right atrium. PMID- 7989074 TI - Percutaneous balloon pericardiotomy for cardiac tamponade. PMID- 7989075 TI - Idiopathic restrictive cardiomyopathy in the very young. PMID- 7989076 TI - Negative U waves in precordial leads in Fallot's tetralogy. PMID- 7989077 TI - Radiofrequency ablation of supraventricular arrhythmias. PMID- 7989079 TI - Long term performance of atrial leads. AB - Long term performance of 163 atrial leads implanted in 158 patients between July 1981 and June 1993 was evaluated. There were 122 DDD and 36 AAI units, with 125 (77%) polyurethane and 38 (23%) silicone leads. One hundred and nine (67%) unipolar and 54 (33%) bipolar leads were used. Patients were followed in the Pacemaker Clinic for 6 to 124 months (mean 50 +/- 39 months). Five patients were lost to follow up. Transient malfunction was observed in 18 cases (sensing 13, pacing 5) within the first 2 weeks. In 13 cases failure to sense subsided spontaneously and in 4 pacing malfunction could be corrected by reprogramming. Lead dislodgement occurred in 4 patients (2.5%), all within the first week. After the 1st month malfunction was uncommon. Between 1 and 12 months undersensing occurred in 4 (2.5%). In 3 cases it could be corrected by reprogramming. In the first year, reoperation was performed in 5 cases for lead related problems (3 dislodgements, 2 insulation failures). Beyond 12 months complications were as follows: failure to sense-8 (5%), failure to pace-3 (2%), insulation break -1 (0.6%). Majority of these problems could be managed by reprogramming. Reoperation was performed in 1 case with insulation break. The pacing mode had to be changed in 5 (3%) patients with dual chamber units who had loss of P wave sensing. During follow-up 98%, 98%, 96%, 95% and 83% of the leads were working satisfactorily at 1,2,3,4 and 9 years respectively. Thus atrial leads have excellent long term performance and an acceptable rate of late malfunction. PMID- 7989078 TI - Cardiac lesions in non-specific aorto-arteritis. An autopsy study. AB - Autopsy data of 58 cases (1958-1986) was analysed for cardiac lesions. The cases were divided into 2 groups; paediatric (23) and adult (35). The heart was normal in 8.7% and 20.5% of the above groups respectively. Rest of the cases showed left ventricular hypertrophy with variable dilatation. Obstructive lesion in the aorta and or renal arteries was present in 91.3% of paediatric and 80.0% of adult cases. Congestive cardiac failure was very common in paediatric group (60.8%) and was not seen in absence of obstructive lesion in the aorta or renal arteries. Histologically the aortic lesion was healed in 70% and 50% of paediatric and adult cases. The commonest additional lesion found, was coronary artery involvement in 11 cases (17%). Ostial stenosis was noted in 7 cases, including 2 in paediatric age group. Epicardial coronaries were involved in 4 cases with infarcts in 4. Aortic incompetence was rare (3.4%). Associated rheumatic mitral stenosis was seen in 2 and healed infective endocarditis in one. Histologically apart from the above mentioned lesions the myocardium showed essentially a response to hypertension. Focal lymphocytic infiltration was seen in 2 children and tuberculosis myocarditis in 3 adults. No case of any other type of myocarditics or cardiomyopathy was seen. In conclusion hypertension and coronary artery disease are the main factors responsible for myocardial failure but additional related or unrelated factors were present in 15.0% cases. PMID- 7989080 TI - A risk scoring system for prediction of coronary heart disease based on multivariate analysis: development and validation. AB - Considering the multifactorial disposition and the need of primordial prevention of coronary heart disease (CHD), a risk scoring system for the prediction of CHD was devised at Govt Medical College, Nagpur, India. In this pair-matched case control study of 154 cases and 154 age and sex matched controls, socioeconomic status, physical inactivity, family history of CHD, type A personality characteristic, cigarette smoking, alcohol consumption, body mass index, diabetes mellitus, hypertension, total serum cholesterol and oral contraceptive use (in women) were studied for association with CHD. The additive risk scoring system based on the results of conditional multiple logistic regression identified five factors, namely, socioeconomic status, physical inactivity, diabetes mellitus, hypertension and toal serum cholesterol with statistical weights of 3,5,2,4 and 5 respectively. On back-validation using receiver operating characteristic (ROC) curve, a total score of 12 was found to be the cut off point above which there was increased risk of CHD. The overall predictive accuracy of this system equivalent to the area under the ROC curve-was 0.7962 (95% Confidence Interval 0.7468-0.8455). On prospective validation using a separate group of 140 cases and 140 controls, the predictive accuracy was found to be 0.6964 (95% Confidence Interval 0.6341-0.7587). Future studies need to assess the risk scoring system in population based studies. PMID- 7989081 TI - Amlodipine monotherapy in chronic stable angina. AB - The efficacy and safety of amlodipine was evaluated in 20 patients with stable exertional angina. Patients with > or = 3 anginal attacks per week in the placebo run-in phase were admitted into a 4 weeks active treatment phase. Amlodipine was administered at a starting dose of 5 mg once daily at bed time, which could be adjusted after 2 weeks to 10 mg once daily if the patient continued to have even a single anginal attack/week. Four weeks of treatment with amlodipine produced a significant (p < 0.05) reduction from baseline in both the mean (+/- SE) number of anginal attacks/week (from 13.3 +/- 1.5 to 1.6 +/- 0.5) and the mean (+/- SE) number of isosorbide dinitrate tablets consumed per week (12.1 +/- 1.5 to 2.6 +/- 0.8). Eighty three percent of patients required an increase in dose to 10 mg daily. No significant change in heart rate, blood pressure, ECG and laboratory results were observed. One patient was withdrawn because of deteriorating angina and sinus tachycardia secondary to beta blocker withdrawal. Worsening of ankle odema was reported in 2 (10%) patients, which was tolerated and disappeared on completing therapy. Thus amlodipine is safe and effective when used as monotherapy in the treatment of chronic stable angina. PMID- 7989082 TI - Serum troponin T in unstable angina--a preliminary report. PMID- 7989083 TI - Surgical correction of the unroofed coronary sinus syndrome. AB - Partially or totally unroofed coronary sinus is usually associated with other anomalies of the heart. In the period of 5 years between January 1987 to October 1992, 13 patients with this syndrome were encountered. All of them had a left superior vena cava draining into left atrium. Of these, 12 were totally unroofed and one had a partial unroofing of the coronary sinus. Associated anomalies encountered included common atria, cortriatriatum, complete A-V canal, tetralogy of Fallot, total and hemianomalous pulmonary venous connection, double outlet right ventricle and atrial isomerism with dextrocardia. Four patients died in the post operative period due to low cardiac output. The nine survivors are all in NYHA class I. At a mean follow up of 4 years, all except one were in sinus rhythm. The other had a nodal rhythm persisting for 4 years. Pericardial baffle redirection of LSVC into the systemic venous atrium which is advocated, was performed in all but one of our earliest patients. Unroofed coronary sinus syndrome is a correctable lesion, the results of which are influenced more by the complexity of the associated anomalies rather than the syndrome per se. PMID- 7989084 TI - Blood conservation in valve surgery. AB - Blood utilization in 40 patients undergoing elective valve surgery was prospectively studied. The patients had valvular lesions of rheumatic origin with a mean age of 29.1 years and a mean preoperative hematocrit of 35.23 +/- 4.16. Blood was removed from all patients after induction of anesthesia and reinfused after bypass (mean 365.12 +/- 66.96 ml). Membrane oxygenator was used in all the patients. All discard suction was routed through a regionally heparinised collecting and processing system, and the resulting red cell concentrate was transfused. At the conclusion of bypass, all blood remaining in the pump oxygenator was also processed by cell saver and used for subsequent reinfusion. Normovolemic anemia was accepted in hemodynamically stable patients. Thirty two patients (80%) received no bank blood or blood products during their entire hospital course. A total of twelve units of whole blood was transfused into eight patients. PMID- 7989085 TI - International classification of rodent tumours. Part I--The rat. 6. Endocrine system. PMID- 7989086 TI - International classification of rodent tumours. Part I--The rat. 7. Central nervous system; heart; eye; mesothelium. PMID- 7989087 TI - Viral hepatitis: a 1994 interim report. AB - A variety of viruses cause many of the disorders that are recognized as acute and chronic liver diseases. Remarkable scientific advances achieved during the past two decades have lead to readily available accurate diagnostic tests for hepatitis viruses designated A through E. Effective vaccines have been developed to prevent hepatitis B and, more recently, hepatitis A. Heightened understanding of the pathogenesis of chronic hepatitis caused by hepatitis B and C suggests several promising therapeutic approaches. Interferon is the sole drug yet proven to be effective in the treatment of some patients with chronic hepatitis B and C. Newer antiviral agents that will be used alone or in combination are under development. PMID- 7989088 TI - The epidemiology of viral hepatitis in the United States. AB - Hepatitis types A, B, and C are the most important forms of viral hepatitis in the Unites States. High-risk sexual and drug use behavior have been associated with epidemics of hepatitis A and endemic transmission of both hepatitis B and hepatitis C. Immune globulin preparations and vaccines have been developed that effectively prevent hepatitis A and hepatitis B. In the absence of such preventive measures, the prevention of hepatitis C will depend on a better understanding of the host and environmental factors that facilitate transmission of this disease. PMID- 7989089 TI - Serologic diagnosis of viral hepatitis. AB - The diagnosis of viral hepatitis is complex, particularly when the five leading causative agents belong to different virus families and evoke distinct immunologic response. This article connects known serologic markers to new methods and guides the ordering and interpretation of contemporary laboratory tests. PMID- 7989090 TI - Molecular diagnostic techniques for viral hepatitis. AB - The five different viruses that cause human viral hepatitis, A, B, C, D, and E share the unique property of hepatotropism. Identification of the nucleic acid sequences of each of these viruses, coupled with the application of recombinant DNA technology, has resulted in the rapid development of molecular diagnostic techniques. Currently, molecular hybridization and polymerase chain reaction are the major diagnostic techniques for viral hepatitis. This review discusses the molecular biology of the five hepatitis viruses, the principles of molecular biological techniques, and their current and future diagnostic applications. PMID- 7989091 TI - Envelope and precore/core variants of hepatitis B virus. AB - The appearance of replication-competent variants of HBV with mutations in the envelope and precore/core and X proteins emphasizes that these proteins are the focus of immune selection pressures in the human host. The presence of an antibody response in the absence of a CTL response may create the ideal selection environment. This occurs in the early phase of passive/active immunization against HBV envelope proteins in neonates born to HBV-infected mothers and also during the emergence of HBeAg-negative variants during and after HBe antigen/antibody seroconversion in chronic HBV carriers with defective CTL responses. The sequence and speed of application of the multiple selection pressures (humoral and possibly cellular) determine the virologic and clinical outcome. When these variant viruses are passed to a new host, in the absence of the immune selection pressures or modified immune pressures that resulted in their selection, a picture clinically different from that seen in the original host may emerge. PMID- 7989092 TI - Hepatitis infection in immunocompromised patients. AB - The current literature fails to address the long-term course of hepatitis infection in the immunocompromised patient, in large part because of the characteristically slow progression of this disease. An overview of the literature available fails to demonstrate evidence that immunosuppression per se promotes progression of hepatitis. In fact, many studies document a relatively low incidence of chronic active hepatitis or cirrhosis in immunocompromised patients; however, properly designed, prospective studies of sufficient numbers of patients with long-term follow-up are not available. Thus, no reliable conclusions are possible at this time. PMID- 7989093 TI - Hepatitis B virus infection in Asian Americans. AB - This article summarizes studies on hepatitis B in the Asian American population and includes prevalence rates among different Asian subgroups, routes of transmission, and sequelae of both perinatal and childhood-acquired hepatitis B virus infection. Rationale for use of hepatitis B immune globulin and hepatitis B vaccine for Asian infants and vaccine for children and seronegative adults is discussed also. Chronic hepatitis B, cirrhosis, and primary hepatocellular carcinoma in adults and screening for early detection of liver cancer are reviewed. PMID- 7989094 TI - Hepatitis E. AB - With the introduction of new, albeit noncommercial, diagnostic tests for the detection of HEV, our understanding of this virus has been greatly enhanced. With these tests, it has been possible to begin a delineation of the process of pathogenesis in infected humans. These tests have also shown us that, at least in some individuals, an IgG response to HEV is long lasting and may confer immunity, and it may be possible to develop a recombinant vaccine against HEV. Contrary to past results, HEV appears to be the most common cause of acute sporadic hepatitis in pediatric populations in endemic regions. HEV has been shown to be a positive sense single-stranded RNA virus that has been tentatively classified as a calicivirus, although its nonstructural proteins exhibit sequence similarity to rubella virus and furoviruses. Despite these advances in our understanding of HEV, it is still necessary to depend on exclusion of hepatitis caused by other viruses to diagnose a hepatitis E infection; however, this situation should change with the anticipated release of commercially available diagnostic tests. PMID- 7989095 TI - Viral hepatitis and hepatocellular carcinoma. AB - Hepatocellular carcinoma (HCC) is one of the more common internal malignancies worldwide and is responsible for over 1 million deaths annually. The causative relationship between chronic hepatitis B and HCC is now beyond doubt, and it is likely that the attributable risk of HCC due to hepatitis C virus (HCV) infection is similar to or greater than that for hepatitis B in some countries. The prospects for preventing HCC with the use of a vaccine against HBV appear excellent. Until a vaccine against HCV becomes available, prevention of HCV related HCC is predominantly dependent on a reduction in transfusion-associated disease. PMID- 7989096 TI - Horizons in fracture surgery. PMID- 7989097 TI - Whither the foot? PMID- 7989099 TI - Stimulating osteogenesis. PMID- 7989098 TI - Growth and repair after injury of the central nervous system: yesterday, today and tomorrow. PMID- 7989100 TI - Laparoscopy in abdominal trauma. PMID- 7989101 TI - The future of ARDS. PMID- 7989102 TI - Setting and living up to national standards for the care of the injured. British Trauma Society. PMID- 7989103 TI - How to persuade surgeons of all specialties to take trauma seriously. PMID- 7989104 TI - Minimally invasive therapy in thoracic injury. PMID- 7989105 TI - Engineering in accidents: vehicle design and injuries. AB - This review has touched superficially on the various mechanisms of injuries to the main classes of road-user casualties, and illustrated some of the desirable vehicle design characteristics which can minimize road trauma. There is still much to be gained by better vehicle design. For occupants, enhanced performance from restraint systems, supplementary airbags, better structural integrity and better compatibility between cars and lorries are obvious areas where known solutions are waiting to be applied. For pedestrians there is an extensive literature outlining the characteristics of friendly vehicle exteriors; many current models of cars are exhibiting some of these properties but better agreement on an optimum specification for the car's exterior is still required. For motorcyclists there is the promise of improved leg protection from energy absorbing fairings although substantial technical debate still surrounds these proposals. For the clinician, a more accurate appreciation of the likely injuries which occur in given collision circumstances can help in diagnosis and treatment. It is for these reasons that some understanding of vehicle design and crash worthiness is worthwhile. PMID- 7989107 TI - Abstracts of the XXIth European Society for Artificial Organs (ESAO) congress. Barcelona, Spain, 20-22 October 1994. PMID- 7989106 TI - Transport of casualties. PMID- 7989108 TI - Presence of immunoassayable transforming growth factor-beta 1 (TGF-beta 1) in breast cyst fluid (BCF): relationship with the intracystic electrolyte and epidermal-growth-factor (EGF) content. AB - We evaluated the presence and distribution of transforming growth factor-beta 1 (TGF-beta 1) in breast cyst fluid (BCF), and its relationship with intracystic epidermal growth factor (EGF). EGF and TGF-beta 1 were determined by radioimmunoassay on 47 BCFs (27 of the Na+/K+ < 3 type and 20 of the Na+/K+ > 3 type). As expected, EGF levels were inversely correlated with the Na+/K+ ratio, and were consequently higher in Na+/K+ < 3 cysts as compared with Na+/K+ > 3 cysts, (p < 0.005). By contrast, TGF-beta 1 levels were directly correlated with the Na+/K+ ratio (p < 0.01), being higher in Na+/K+ > 3 cysts, though not significantly (p = 0.057). A significant negative relationship was found between EGF and TGF-beta 1 concentration. When the analysis was performed separately in the 2 cyst sub-populations, EGF and TGF-beta 1 were found to be negatively and significantly correlated in Na+/K+ < 3 cysts only (p < 0.01). Our results demonstrate that Na+/K+ < 3 cysts contain high levels of EGF, a growth stimulating factor, and very low levels of TGF-beta 1, a growth-inhibiting factor. This may provide an explanation for the higher risk of breast cancer observed in women with Na+/K+ < 3 cysts. Our results also suggest that EGF accumulation in this type of cysts might be regulated by TGF-beta 1. PMID- 7989110 TI - Enzyme-linked immunosorbent assay (ELISA) for IgA and IgG antibodies to Epstein Barr-virus ribonucleotide reductase in patients with nasopharyngeal carcinoma. AB - 661 bp coding for the carboxyl end of the large sub-unit of EBV ribonucleotide reductase was cloned into the pMal plasmid vector. Purified recombinant protein was tested in IgG and IgA ELISAs. For the IgG assay, 81 out of 100 NPC patients tested positive, whereas for the IgA assay, 60 tested positive. Among 100 normal individuals, I tested positive for the IgG assay and 9 tested positive for the IgA assay. The IgG assay picked up 6 out of 19 NPC sera which were IFA-VCA- and IFA-EA-negative for IgA antibodies. Hence the recombinant ribonucleotide reductase could have good potential as a diagnostic test for NPC or could serve as a complementary test to IFA. PMID- 7989109 TI - Increased risk of colorectal cancer among smokers: results of a 26-year follow-up of US veterans and a review. AB - To clarify the relationship between tobacco use and risk of colorectal cancer, we evaluated a cohort of 248,046 American veterans followed prospectively for 26 years. In comparison with veterans who had never used tobacco, the risk of death was significantly increased for colon cancer and rectal cancer among current and former cigarette smokers and among pipe or cigar smokers, controlling for social class and occupational physical activity. Rectal-cancer risk was also significantly elevated among users of chewing tobacco or snuff. For both sites, risk increased significantly with pack-years, earlier age at first use, and number of cigarettes. These results reinforce 2 recent reports of the association of cigarette smoking and colorectal cancer in men and women. Inconsistencies in the findings of earlier epidemiologic studies appear to be due in large part to differences in length of follow-up or in choice of controls. Studies with at least 20 years of follow-up or population-based controls have tended to find elevated risk with tobacco smoking, while those with shorter follow-up or hospital controls have not. This, plus the strength and consistency of the association of smoking and colon polyps, suggest that smoking may primarily affect an early stage in the development of colon cancer. If this association is causal, tobacco use may be responsible for 16% of colon-cancer and 22% of rectal cancer deaths among these veterans. PMID- 7989111 TI - Genotypic analysis of Epstein-Barr virus isolates associated with nasopharyngeal carcinoma in Chinese immigrants to the United States. AB - EBV genotypes of first- and second-generation Chinese diagnosed with nasopharyngeal carcinoma in the United States were analyzed by PCR techniques. Previous studies showed a geographical distribution of genotypically distinct sub types of EBV. Viruses detected at a higher frequency among Chinese NPC patients (Cf) were distinguished from those found in the majority of Caucasian NPC patients (DF) in the United States by polymorphisms in the BamHI F and I regions. Exploiting this distinction, we analyzed the biopsies of Chinese immigrants in the United States for their C/D and F/f genotypes to evaluate the importance of retention of the Cf virus among Chinese NPC patients in a geographical area where the DF virus prevails. This study shows that approximately 45.5 to 50% of first- and second-generation Chinese NPC patients in California harbor the Cf virus, which is present in only 8% of Caucasian NPC patients in California. It is interesting that, while only 48% of the viral isolates from immigrant Chinese to California harbor the "f" variant, 96% harbor the type-C viruses. PMID- 7989112 TI - The common molecular genetic alterations in Dukes' B and C colorectal carcinomas are not short-term prognostic indicators of survival. AB - Our study was undertaken to determine the prognostic significance of several common genetic alterations observed in colorectal carcinomas. We have previously analysed loss of heterozygosity of the MCC, APC, p53 and DCC tumour suppressor gene loci as well as p53 gene mutations and protein over-expression in a series of 100 Dukes' stage B and C colorectal tumours obtained at surgery. To extend our observations of alterations that may occur in these tumours, mutations to the c Ki-ras oncogene and APC tumour suppressor gene were detected by PCR single-strand conformation polymorphism analysis. Short-term follow-up revealed no significant association between overall patient survival and any single, or combination of, genetic alteration(s). Surprisingly, patients whose tumours showed evidence of p53 protein over-expression/accumulation by immunocytochemistry (ICC) had a significantly better prognosis (p = 0.039) than those whose tumours had no p53 ICC reactivity. PMID- 7989113 TI - The decreased expression of CD3 zeta chains in cancer patients is not reversed by IL-2 administration. AB - The mechanisms underlying the impaired immune response frequently observed in cancer patients are poorly understood. Recently, a decreased expression of the signal-transducing CD3 zeta chains has been shown to occur in patients with colorectal or renal-cell carcinoma. Here, we have investigated the expression of the zeta molecule on lymphocytes from patients with advanced cancers including renal-cell carcinoma (n = 21), hepatic colorectal carcinoma metastases (n = 6), head-and-neck squamous-cell carcinoma (n = 7) or miscellaneous tumors (n = 7), using flow cytometry analysis of PBMCs with monoclonal antibody specific for the cytoplasmic domain of the zeta chain. The same analysis was also performed with patients undergoing IL-2 therapy (from 5 days up to 3 months i.v. or s.c.). PBMCs from patients (n = 41) showed a significant decrease in expression of the zeta chains as compared to the levels found in lymphocytes from healthy controls (n = 15), which was not reversed by IL-2 administration. Together, these results suggest that an alteration in the expression of the zeta-chain-transducing element in PBMCs may be a common cause of progressive immunosuppression in advanced cancer patients and that IL-2 is not sufficient to reverse this situation in vivo. PMID- 7989114 TI - Intake of fried meat and risk of cancer: a follow-up study in Finland. AB - It has been suggested that mutagens in fried meat may be involved in the cancer process. Therefore the relationships between intake of fried meat and subsequent risk of cancers at different sites were studied among 9,990 Finnish men and women, 15-99 years of age and initially free of cancer. The baseline study was carried out in 1966-1972, and cases of cancer were identified through data linkage with the Finnish Cancer Registry. During a 24-year follow-up, 853 cancer cases were diagnosed. The intake of fried meat was estimated from a dietary history interview covering the total diet of the participants during the previous year. There was a positive association between fried meat intake and the risk of female-hormone-related cancers, i.e., cancer of the breast, endometrium and ovary combined. The relative risk of these cancers combined between persons in the highest and lowest tertiles of daily intake of fried meat adjusted for age, personal characteristics and intake of other main food groups was 1.77 (95% confidence interval = 1.11-2.84). Pancreatic and nervous system cancers also presented non-significant suggestive associations. No associations were observed with respect to other single cancer sites studied or to all sites of cancer combined. Further epidemiological efforts are needed to ascertain the potential link between fried-food mutagens and cancer risk. PMID- 7989115 TI - Menstrual and reproductive factors and gastric-cancer risk in women. AB - To understand possible correlates of the systematically higher gastric-cancer rates in males than in females, we investigated the role of menstrual, reproductive and hormonal factors in females, using data from a case-control study conducted in Northern Italy. Cases were 229 post-menopausal women with incident, histologically confirmed gastric cancer, and controls were 614 post menopausal women in hospital for acute, non-neoplastic, non-digestive-tract conditions. After allowance for age, education, family history, and selected dietary correlates of stomach cancer, a reduced gastric-cancer risk was observed in women with later menopause (odds ratio, OR = 0.6, p value for trend < 0.05), and longer duration of fertile life (OR = 0.7, but the trend in risk was not significant). The risk of gastric cancer was elevated in multiparous women (OR = 1.7 for 3 and 1.9 for > or = 4 births as compared to nulliparae). No association was observed with age at menarche, age at first birth, and with number of spontaneous or induced abortions. Ever-users of oral contraceptives had a non significant increased risk (OR = 1.3), and users of oestrogen-replacement treatment a non-significant reduced risk (OR = 0.5). Although the association with each factor was moderate, and the interpretation of these findings is not straightforward, these results are compatible with the hypothesis that some role is played by (endogenous and exogenous) female hormones in the process of gastric carcinogenesis. PMID- 7989116 TI - Brain cancer incidence, mortality and case survival: observations from two Australian cancer registries. AB - Data from 2 Australian cancer registries covering a population of 1.7 million people were combined for the purposes of analysing brain cancer incidence, mortality and survival patterns for the time period 1978 through 1992. A total of 1,752 cases of primary brain cancer were registered, representing age standardised incidence rates of 6.7 per 100,000 in men and 4.6 in women. Histological confirmation was available for 94% of cases. The incidence rate among persons aged 75 or over was higher during 1986-1992 than during 1978-1985, the rate for men increasing from 16.3 to 26.2 and that for women increasing from 9.7 to 18.0. The largest increases in this age group occurred for cases of glioblastoma multiforme. During the study period, 1,411 brain cancer deaths were notified to the 2 registries at age-standardised rates of 5.3 in men and 3.4 in women. Mortality rates among persons aged 75 years or older were higher during 1986-1992 than 1978-1985, increasing from 15.7 to 28.4 in men and from 10.1 to 15.3 in women. Only among men aged 15-49 years was a decline in mortality rates observed, from 3.3 to 2.4. Survival analyses indicated that age and histological type were the most powerful prognostic indicators. There was no improvement in 5 year survival for any of the age groups or histological types. An improvement in 36-month survival was noted for the 15-49 year age group diagnosed with gliomas other than glioblastoma multiforme. PMID- 7989117 TI - Linkage analysis in familial melanoma kindreds to markers on chromosome 6p. AB - Malignant melanoma occurs as a familial cancer in 5%-10% of cases, where it segregates in a manner consistent with autosomal dominant inheritance. Evidence from cytogenetics, fine mapping studies of deletions in melanomas and recent linkage studies supports the location of a human melanoma predisposition gene on the short arm of chromosome 9. Evidence also exists for a melanoma gene on Ip, indicating genetic heterogeneity for melanoma predisposition. Previous studies have also reported findings suggestive of linkage of some melanoma families to the HLA region on the short arm of chromosome 6 (6p), indicating the possibility of even greater heterogeneity. To further define the possible effect of a gene within the HLA region on melanoma susceptibility, we have typed 7 simple tandem repeat polymorphisms (STRPs) from 6p in 16 Australian melanoma kindreds. Maximum 2-point LOD scores ranged from 1.13 (theta = 0.2) to 2.03 (theta = 0.15) for 4 contiguous markers flanking the HLA complex, and multi-point analysis gave a peak LOD score of 1.64, 24 centimorgans telomeric to D6S109. However, extended haplotype analysis of these markers showed that a region between D6S105 and HLAF segregated with melanoma in 5/16 families. These results are surprising given that the same cohort of families has previously been shown to be linked to chromosome 9. One interpretation of the current findings is that melanoma susceptibility in some families may result from a gene mapping within the HLA region of chromosome 6p. PMID- 7989118 TI - Incidence and risk factors for childhood brain tumors in the Ile de France. AB - A case-control study investigating risk factors for childhood brain tumors was conducted in the Ile de France (Paris region). During a 2-year period (1985-1987) 109 newly diagnosed cases were identified and, of these, 75 could be interviewed. In the same region, 113 population controls, frequency-matched for year of birth, were interviewed. Odds ratios adjusted for child's age and sex and for maternal age were estimated for each risk factor present in utero or during childhood by conditional logistic regression. Statistically significant associations were found for the following risk factors: farm residence, cat scratches, home treated with pesticides, passive smoking, family history of cancer, antihistamine intake. Intake of vitamin supplements during childhood was associated with a decrease in risk. This study is part of a multicentric case-control study coordinated by the International Agency for Research on Cancer and its results will be compared for consistency, and pooled with those of other centers using the same protocol. PMID- 7989119 TI - Identification and characterization of autocrine-motility-factor-like activity in oral squamous-cell-carcinoma cells. AB - A human oral squamous-cell-carcinoma cell line, HOC313, was found to produce a factor which stimulates cell motility in an autocrine manner. The motility factor of HOC313 cells also promoted the locomotory activity of B16 murine melanoma cells reported to be sensitive to autocrine motility factor (AMF). HOC313 cells were found to express a large amount of AMF-receptor mRNA. In addition, the cell motility activity of HOC313 cells was completely blocked by pertussis toxin, a known inhibitor of AMF activity, suggesting that the motility factor of HOC313 cells may be AMF or a closely related factor. Immunocytochemical analysis has revealed that the AMF-like factor of HOC313 cells diminishes the cell-surface expression of adhesive molecule E-cadherin. These results suggest that down regulation of E-cadherin may be involved in the cell-motility activity induced by the AMF-like factor of HOC313 cells. PMID- 7989120 TI - P-glycoprotein expression in the Golgi apparatus of multidrug-resistant cells. AB - The surface and intracellular expression of mdrI-P-glycoprotein in parental drug sensitive human breast cancer cells (MCF-7) and their multidrug-resistant (MDR) variants has been studied by using the monoclonal antibodies (MAbs) MM4.17 and MRK-16, which recognize 2 different epitopes of the drug efflux pump molecule. Fluorescence microscopic observations showed that P-glycoprotein, in addition to being located at the cell surface, can also be found in the Golgi apparatus of resistant cells. To confirm this finding, Golgi apparatus and P-glycoprotein were double-labelled with wheat-germ agglutinin (WGA) and MAb MM4.17. Laser scanning confocal microscopy indicated that, in MDR cells, Adriamycin mainly accumulated cytoplasmically in a perinuclear region. This accumulation proved to be modulated by pre-treatment with verapamil or ATP depletion. Moreover, the vital staining of Adriamycin-treated MDR cells, performed with the fluorescent lipid N-[7-(4 nitrobenzo-2-oxa-1,3-diazole)]- 6-aminocaproyl sphingosine (C6-NBD-ceramide), revealed that the anthracyclinic antibiotic was located in the Golgi apparatus. All these results indicate that the drug transporter is located in the Golgi apparatus, in which Adriamycin molecules also accumulate. PMID- 7989121 TI - Effective anti-metastatic melanoma vaccination with tumor cells transfected with MHC genes and/or infected with Newcastle disease virus (NDV). AB - The therapeutic efficacy of active immunization with B16-F10.9 melanoma cells transfected with syngeneic major histocompatibility complex (MHC) class-I genes, modified by infection with Newcastle Disease virus (NDV) or modified by both treatments, was compared. B16-F10.9 tumor-bearing mice were treated at various stages of tumor growth and metastasis with irradiated, modified tumor-cell vaccines. Irradiated tumor cells and H-2Db transfectants did not stimulate anti tumor immunity while H-2Kb transfectants and NDV-modified F10.9 cells showing low and high expression of MHC class-I genes efficiently prevented metastasis of small established tumors. NDV-modified parental-cell vaccines functioned optimally and improved overall survival by about 60%, also at early stages of metastasis establishment. A synergistic effect of H-2Kb expression and virus modification on rejection of micrometastases was observed in mice bearing advanced tumors. Postoperative vaccination of mice carrying multiple metastases with NDV-modified vaccines caused significant, but incomplete, reduction of metastatic tumor load. The therapeutic effect of NDV-modified tumor vaccines was dependent on multiple immune mechanisms. Depletion of CD8, CD4 or NK cells by in vivo treatment with monoclonal antibodies reversed the immunotherapeutic effects of the vaccine. Thus, tumor xenogenization and gene modification may act synergistically to vaccinate against advanced tumors, while single modalities can effectively vaccinate against metastasis at early stages of tumor growth. PMID- 7989122 TI - Immunization with anti-idiotype monoclonal antibodies bearing the internal image of the renal-cell carcinoma-associated antigen G250 induces specific cellular immune responses. AB - We have previously isolated and characterized 6 anti-idiotype antibodies (Ab2s) directed against monoclonal antibody G250 (MAbG250) which reacts with a tumor associated antigen (TAA) expressed in a large proportion of human renal-cell carcinomas (RCC). These 6 Ab2s (NUH31, 51, 71, 82, 91: IgG1, NUH44: IgG2a) showed MAbG250 binding site specificity and induction of anti-TAA antibody resembling MAbG250 (so-called AbI') in rabbits, indicating that they are internal image antibodies. To investigate whether these Ab2s could induce G250-TAA-specific cell mediated immunity, delayed-type hypersensitivity (DTH) tests were carried out with G250 antigen-positive and/or -negative cells in the ears of BALB/c mice. Mice primed with Ab2 showed antigen-specific DTH responses, whereas no significant DTH response was observed with G250-negative cells. This antigen specific DTH could be transferred to naive mice by lymphocytes harvested from Ab2 sensitized mice. In addition to the classical DTH responses observed 24 and 48 hr after tumor challenge, an early-phase antigen-specific hypersensitivity response was seen 2 hr after challenge. This early component of the specific hypersensitivity reaction but not the classical DTH could be transferred to naive mice by serum from Ab2-sensitized mice, indicating that the early reaction was due to serum factors. These findings demonstrate that all Ab2s induced tumor specific cellular immune responses directed against human RCC, and suggest that they may be useful as RCC-TAA surrogates, i.e., as tumor vaccines for RCC patients. PMID- 7989123 TI - Effects of type-I and -II interferons on 90K antigen expression in ovarian carcinoma cells. AB - Antigen 90K is produced by several tumor-cell lines and by patients with cancer. Its function has not yet been clarified, although recent reports suggest that it plays a role in the tumor-host relationship--for example by stimulation of natural killer and lymphokine-activated killer-cell activity. Previous studies have indicated that 90K expression may be under the influence of interferon alpha. Here, we provide evidence that both interferon-alpha and -gamma can enhance the secretion of 90K and augment the level of specific mRNA expression in 3 ovarian carcinoma cell lines (OVCAR-3, HTB-77 and SKOV-6). However, interferon gamma leads to depletion of cellular 90K whereas interferon-alpha increases both secreted and cellular 90K levels. In equimolar concentrations, Interferon-alpha was always superior to interferon-gamma in augmenting 90K protein or mRNA levels. Combinations of TNF with interferon-gamma were highly synergistic both in reducing cell proliferation and in increasing 90K secretion and mRNA expression. This synergism was seen to a lesser extent with interferon-alpha. PMID- 7989124 TI - Lysosomes as photochemical targets. AB - Sulfonated tetraphenyl porphines (TPPSn) are photosensitizing dyes that localize in lysosomes of NHIK 3025 cells. In order to elucidate the mechanisms of cell inactivation by photochemical treatment with TPPSn, lysosomal enzyme inactivation and release of lysosomal contents were examined after treatment. In cells treated with TPPS4 and light, the lysosomal enzymes beta-N-acetyl-D-glucosaminidase (beta AGA) and cathepsin(L+B) were almost completely inactivated and no enzyme activities were released from the lysosomes. In contrast, a maximum of 30 and 50% of the initial beta-AGA activity was released from lysosomes after treatment with TPPS1 and TPPS2a, respectively. Forty per cent of the initial beta-AGA activity was released after treatment with TPPS2a and a non-cytotoxic dose of light. After such a treatment only approximately 10% of the initial cathepsin activity was found in the cytosol fraction and in all other cases no cathepsin activity was recovered in the cytosol fraction after photochemical treatment. It was found that the constituents of the cytosol partly inhibited cathepsin activity. This inhibitory effect was not influenced by the photochemical treatment, neither was the colony-forming ability of photochemically treated cells influenced by pre treatment with the cathepsin inhibitor E64. The present results indicate that NHIK 3025 cells are not killed by lysosomal disruption after photochemical treatment. This is partly due to photochemical inactivation of the lysosomal enzymes and to the action of cytosolic cysteine cathepsin inhibitors. The present results also indicate that cells can survive a partial lysosomal disruption. PMID- 7989125 TI - Intraperitoneal photodynamic therapy in the rat: comparison of toxicity profiles for photofrin and MTHPC. AB - Toxicity studies for intraperitoneal photodynamic therapy (IPPDT) were performed in Wag/RijA rats, using specially designed light delivery blocks for proper light distribution and light dosimetry. A recently developed photosensitizer mesotetrahydroxyphenylchlorin (mTHPC), excited at 652-nm wave-length, was compared with Photofrin (630 nm). Toxicity profiles for various sensitizer doses, light fluences and time intervals were investigated. A light fluence of 15 J.cm-2 delivered to the entire peritoneum 24 hr after 5 mg Photofrin per kg i.v. induced reversible impairment of intestinal, liver and kidney function. A dose of 0.2 mg mTHPC per kg i.v. followed by 6 J.cm-2 at 72 hr appeared to be equitoxic to the intestines; however, functional tests revealed little effect for this mTHPC mediated IPPDT regime on liver or kidney. Histology demonstrated focal irreversible damage to the kidneys for both photosensitizers, not reflected in functional impairment. Light doses of 25 to 30 J.cm-2 at 24 hr after Photofrin or 8-12 J.cm-2, 72 hr after mTHPC caused lethal toxicity in the first 2 weeks due to intestinal damage. Higher light doses caused a shock syndrome and rhabdomyolysis resulting in death within 20 hr for both photosensitizers. In conclusion, maximum tolerable schedules for whole-abdomen IPPDT were defined for Photofrin and mTHPC. Both photosensitizers caused similar toxicity profiles depending on drug dose, light fluence and time interval. PMID- 7989127 TI - Modifications of the anti-oxidant metabolism during proliferation and differentiation of colon tumor cell lines. AB - The anti-oxidant metabolism was studied at different times after sub-culture in 2 colon cell lines previously characterized for their growth and differentiation properties. The HT29 cell line is mainly composed of proliferative and undifferentiative cells, while the derived 5-fluorouracil (FUra)-adapted cells undergo growth-dependent differentiation, which is complete at post-confluence. In the 2 cell lines, all the anti-oxidant parameters studied appeared to be related to proliferation, with increased activity of superoxide dismutase (SOD) 1 and 2, catalase (CAT), glutathione peroxidase (GPX), glutathione reductase (GSR), and glutathione transferase (GST), and decreased glucose-6-phosphate dehydrogenase (G6PD) activity and glutathione content, in parallel with slowing down of proliferation. At post-confluence, these metabolic parameters remained stable, except for GPX activity, which continued to increase, and CAT activity, which decreased. The amounts of SOD1, SOD2 and CAT immunoreactive proteins, estimated by Western blotting, appeared to be correlated to their respective enzymatic activities. SOD1, CAT and GST activity and glutathione content, which remained at similar levels in the 2 cell lines for all times studied, appeared unrelated to the differentiation process. GSR and GPX activity, which was lower in FUra-adapted than in parental cells only at post-confluence, could be considered as markers of differentiated cells. The higher SOD2 and lower G6PD activity observed in FUra-resistant cell in comparison with parental cells at all times after sub-culture could be characteristic both of differentiative and of differentiated cells. Interestingly, cytogenetics have previously indicated that deletions of the long arm of chromosome 6, which carry the gene for SOD2, were frequently observed in parental but not in FUra-adapted cells. These results demonstrate that modifications of the anti-oxidant metabolism occur in relation with proliferation and differentiation, and suggest a particular role for SOD2 in these cellular processes. PMID- 7989126 TI - Cellular immune response to human renal-cell carcinomas: definition of a common antigen recognized by HLA-A2-restricted cytotoxic T-lymphocyte (CTL) clones. AB - Cytotoxic T lymphocyte (CTL) clones directed against autologous renal-cell carcinoma (RCC) cell lines were generated by mixed lymphocyte/tumor-cell culture (MLTC) using peripheral blood lymphocytes (PBL). A CD8+, CD4- CTL clone MZ1257 CTL 5/30 with high cytolytic activity for the autologous tumor cell line MZ1257 RCC was established. No lysis of the autologous EBV-transformed B lymphocytes (EBV-B) or K562 cells was observed. A panel of HLA-A2-matched allogeneic RCC lines was recognized by CTL 5/30. Further specificity analysis showed a cross reactivity with HLA-A2-matched allogeneic tumor cells of various origins, especially melanoma. CTL 5/30 was also cross-reactive with several HLA-A2 positive allogeneic normal kidney cells in culture. The restriction element identified for CTL 5/30 was HLA-A2, as shown by blocking of cytotoxicity using an anti-HLA-A2 monoclonal antibody (MAb) and by resistance of an HLA-A2-negative melanoma variant SK29-MEL. 1.22 against lysis by CTL 5/30. In this report we demonstrate HLA-A2-restricted recognition of a T-cell-defined antigen on autologous renal-cancer cells. This antigen is also expressed and recognized in association with HLA-A2 on normal kidney cells in culture and other HLA-A2 positive tumor cells. It may therefore be a normal differentiation antigen to which tolerance is incomplete in the renal-cell cancer system investigated. PMID- 7989128 TI - Chimeric transcripts with an open reading frame are generated as a result of translocation to the Pvt-1 region in mouse B-cell tumors. AB - Some mouse plasmacytomas exhibit a t(6;15) chromosomal translocation in which the breakpoint resides within the Pvt-1 locus located 260 kilobases (kb) downstream of c-myc on mouse chromosome 15. In this report, we show that the Pvt-1 locus does not exhibit allelic exclusion in that Pvt-1 transcripts continue to be expressed from the non-translocated allele in t(6;15) plasmacytomas. From the translocated allele, we find chimeric transcripts containing a short 57-bp segment of Pvt-1 (termed Pvt-1a) spliced directly to the immunoglobulin constant region sequence (Ig-Ck). These short transcripts have replaced a Jk segment with a trytophan residue via RNA splicing and contain a continuous open reading frame (ORF) from Pvt-1a through Ck. Since this Pvt-1a/Ck transcript is found in all 3 t(6;15) plasmacytomas examined, regardless of the location of the chromosomal breakpoint, we suggest that the Pvt-1a/Ck chimera may have a functional role in the development of mouse plasmacytomas. PMID- 7989129 TI - The protein kinase C inhibitor, CGP 41 251, reverses decreased daunomycin uptake in a human drug-resistant ovarian carcinoma cell line. PMID- 7989130 TI - Adenosine as a possible inhibitor of killer T-cell activation in the microenvironment of solid tumours. PMID- 7989131 TI - Recipient-mediated effect of a traditional Chinese herbal medicine, ren-shen-yang rong-tang (Japanese name: ninjin-youei-to), on hematopoietic recovery following lethal irradiation and syngeneic bone marrow transplantation. AB - Ren-shen-yang-rong-tang (Japanese name: Ninjin-youei-to, NYT), a traditional Chinese herbal medicine, was evaluated for recipient-mediated effect on hematopoietic recovery in a murine model of syngeneic bone marrow transplantation (BMT). BALB/c recipient mice were preconditioned with a lethal total body irradiation (TBI) at a dose of 6.5 Gy and transplanted with syngeneic bone marrow (BM) cells. NYT treatments, given intraperitoneally (i.p.) once per day for 3 consecutive days in a dose of 0.625 mg, were performed either before or after TBI and BMT to assess any recipient-mediated effect of this compound. NYT pretreatment was as effective as NYT posttreatment in enhancing the total number of colony-forming unit erythroid (CFU-E) and colony-forming unit granulocyte macrophage (CFU-GM) per marrow and spleen after TBI and BMT. NYT pretreatment caused a significant increase in marrow and splenic CFU-E and CFU-GM numbers over a prolonged period following TBI and BMT, and affected late-stage erythropoiesis (CFU-E) more profoundly than early-stage erythropoiesis (burst-forming unit erythroid, BFU-E). NYT pretreatment significantly accelerate recovery of not only erythrocyte and leukocyte counts but also platelet counts after transplantation with a limited number (1 x 10(5)) of BM cells. The same treatment, however, was significantly less effective in hematopoietic recovery after transplantation with a minimal number (1 x 10(4)) of BM cells, indicating that NYT accelerates recovery of donor-derived rather than recipient-derived cells.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7989132 TI - Inhibition of human neutrophil elastase and cathepsin G by a biphenyl disulfonic acid copolymer. AB - The sulfated polymer MDL 101,028 was found to be a potent-inhibitor of both human neutrophil elastase (HNE) and human neutrophil cathepsin G (CatG). Cleavage of synthetic substrate by HNE was inhibited by MDL 101,028 with an IC50 of 40 nM, while CatG was inhibited with an IC50 of 80 nM. Degradation of a macromolecular connective tissue substrate (cartilage proteoglycan) by HNE or CatG was inhibited by MDL 101,028 with an IC50 of approximately 10 microM. MDL 101,028 at concentrations of 4, 10 and 25 microM inhibited degradation of cartilage proteoglycan by human neutrophil lysate or stimulated human neutrophils by 54%, 70% and 79%, and 31%, 47% and 73%, respectively. Acute pulmonary injury resulting from the intratracheal (i.t.) instillation of HNE in rats was inhibited by 48%, 90% and 90% at concentrations of MDL 101,028 of 1.1 mg/kg, 2.8 mg/kg and 11 mg/kg. The duration of action of the compound after i.t. instillation was between 2 and 4 h. These results suggest that sulfated polymers such as MDL 101,146 may be useful as inhibitors of HNE-mediated lung injury. PMID- 7989133 TI - CD4-8- T-cells increase in MRI/lpr mice treated with thymic factors. AB - The in vivo effect of thymic factors on immature lymphocytes was analysed in MRL/lpr mice. This strain carries a genetic defect that causes during their life cycle a block of T-cell differentiation and abnormal proliferation of CD4-8- (double-negative, DN) T-lymphocytes. In vivo administration of four preparations of thymic factors, thymopentin (TP-1), thymopoietin (TP-5), thymolymphotropin (TLT), and thymomodulin (TMD) into young (2-month-old) MRL/lpr mice induced a significant increase of DN T-cells both in the thymus and in the peripheral lymph nodes, with a concomitant decrease of double-positive (DP) T-cells in the thymus and of single-positive (SP) T-cells in the lymph nodes. The level of DNA fragmentation measured as propidium iodide fluorescence was increased in the thymus population of young mice and in the lymph node population of old mice treated with TLT. SCID mice transplanted with lymph node cells from MRL/lpr donors (MRL-->SCID) developed graft versus host (GvH) reaction due to the activation of MRL CD8+ alloreactive T-cells. This model was used to analyse the effect of TMD/TLT in vivo on MRL cell proliferation and expansion; in fact, spleen cells from MRL-->SCID mice after treatment with TMD/TLT showed an increased cell proliferation, and an expansion of DN T-cells with a concomitant decrease of SP cells (both CD4+ and CD8+ cells). Decreased SP cell numbers in this context could explain why TMD/TLT treatment of SCID mice engrafted with MRL cells increased their survival compared to untreated MRL-->SCID mice. PMID- 7989134 TI - Biological activities of chemically synthesized N-acylated serine-linked lipid A analog in mice. AB - The mitogenicity, lethal toxicity and antitumor activity against Meth A fibrosarcoma and the induction of tumor necrosis factor (TNF) of chemically synthesized N-acylated serine-linked nonphosphorylated acylglucosamine-derived lipid A analog (A-601, A-602 and A-603) were determined. Compounds A-603 (with (R)-3-tetradecanoyloxytetradecanoyl at the C-2 position) and A-103 (2,3 acyloxyacylglucosamine-4-phosphate) induced significant incorporations of [3H]thymidine into splenocytes of C3H/He mice at concentrations ranging from 6.25 to 100 microM. The mitogenicity of A-601 and A-602 (with tetradecanoyl at the C-2 position) exhibited a lower activity than of A-603. Compounds A-601 and A-603 showed almost the same lethality at doses from 1 to 50 nmol/mouse in C57BL/6 mice loaded with D-galactosamine, whereas A-103 caused the death of two out of six mice at a dose of 25 nmol/mouse. A-601 and A-603 showed weak antitumor activity against Meth A fibrosarcoma in BALB/c mice, but there was no enhancement of antitumor activity by a combination of A-603 with muramyl dipeptide. Peritoneal macrophages, stimulated with A-601, A-602 or A-603, caused production of TNF which induces L929 cell lysis in vitro. But the activity of A-603 among the compounds on TNF-production was the highest. These findings indicate that the linkage of nonphosphorylated acylglucosamine and N-acylated serine affects the expression of the biological activity. PMID- 7989135 TI - Growth hormone inhibits normal B-cell differentiation and neutrophils' chemotaxis in vitro. AB - In acromegalic patients we have previously described a low ability of B lymphocytes to differentiate into plasma cells under PWM stimulation, and a decreased chemotaxis of polymorphonuclear leukocytes (PMN) towards N formylmethionylphenilalanine (FMP). In this study we examined the effect of exogenous GH over these immune functions in normal cells. PMN were purified by dextran sedimentation, incubated with recombinant human GH (0 to 20 ng/ml) and subjected to stimulation with FMP. PBMC were cultured with or without PWM, in the presence of GH (between 0 and 100 ng/ml). Plasma cells were determined as hemolysis plaque forming cells and also by immunofluorescence. GH, in a dose dependent way, decreased directed migration of PMN (5 ng/ml: 1.787 +/- 148 microns; 10 ng/ml: 1.581 +/- 221 microns; 20 ng/ml: 1.569 +/- 149 microns, all as mean +/- S.E.M.), when compared to similar values of untreated PMN (0 ng/ml 2.085 +/- 139 microns). GH treatment did not modify spontaneous migration. Net migration showed the same pattern as directed migration. GH decreased dose dependently the PWM-driven differentiation of B-lymphocytes into plasma cells to 60% of the basal level. Although not significantly, GH tended to increase spontaneous B-cell differentiation. These results could account for the already described defect in B-cell differentiation and PWN chemotaxis in acromegaly, emphasizing the relationship between the endocrine and immune systems. PMID- 7989136 TI - LCB 2183 inhibits the inflammation associated with oxazolone-induced contact sensitivity. AB - LCB 2183, an anti-allergic and potential anti-asthma compound, has been investigated for its ability to inhibit contact sensitivity in the mouse. The delayed response to epicutaneous hapten challenge in this model is a classical T cell-mediated inflammatory reaction which is dependent on an early initiation phase. Both the early and late components of oxazolone-induced contact sensitivity were inhibited by oral administration of LCB 2183 in a dose-dependent manner. The drug appears to act on the efferent limb of the response since administration before hapten challenge was effective, while administration before the initial sensitization was not. LCB 2183 acts early in the cascade of events leading to inflammation, since the initiation phase of the response was inhibited; nonetheless, an effect of the drug on the late acting inflammatory cells cannot be ruled out. In comparison with oral prednisolone, which was also able to inhibit both the early and late components of the response, LCB 2183 was less active. Sodium cromoglycate and nedocromil sodium, which are poorly absorbed from the gastrointestinal tract, were tested by intraperitoneal administration. Neither of these agents significantly altered the delayed response and only nedocromil sodium had a limited inhibitory effect on the early initiation phase. Thus, in this model, LCB 2183 demonstrated more anti-inflammatory potential and resembled prednisolone more closely than either nedocromil sodium or sodium cromoglycate. The possible relevance of these effects in relation to the inflammation which characterizes human asthma is considered. PMID- 7989137 TI - Inhibition of lymphocyte proliferation by the anti-arthritic drug sinomenine. AB - The effect on lymphocyte proliferation of sinomenine, a pure alkaloid extracted from the Chinese medical plant Sinomenium acutum was investigated in vitro using mouse spleen cells and human peripheral blood mononuclear cells. It could be demonstrated that sinomenine markedly inhibited [3H]thymidine incorporation in mouse spleen cells activated with concanavalin A (IC50 = 400 microM) or by two way mixed lymphocyte culture (IC50 = 60 microM) and also in human peripheral blood mononuclear cells activated with phytohemagglutinin, 12-O tetradecanoylphorbol-13-acetate plus ionomycin, or mixed lymphocyte culture (IC50 ranging from 34 to 129 microM). Time kinetic experiments revealed that sinomenine was effective only when added within the first 48 h after the onset of mixed lymphocyte culture, which lasted for 5 days. Inhibition of lymphocyte proliferation by sinomenine was reversible. Accordingly, the drug showed no direct cytotoxicity in our cellular systems and had no inhibitory effect on the proliferation of the cytokine-independent growth of the human leukaemic T-cell lymphoblast cell line Jurkat. It can be considered that these anti-proliferative effects are part of the anti-inflammatory and anti-arthritic mechanisms of sinomenine obvious in clinical trials. PMID- 7989139 TI - Freud's treatment of a narcissistic patient. AB - The newly-published correspondence between Freud and Ernest Jones reveals Freud's views on the treatment of a severely narcissistic patient in 1922, just prior to his writing 'The Ego and the Id'. His formulation centres on 'a deep sense of guilt ... a conflict between Ego and Ideal ... whenever it is revived she projects her self-criticism to other people, turns her pangs of conscience into sadistic behaviour'. He aims toward 'reconciliation of her Ideal to her Ego', and emphasises her need for his friendly support in order to tolerate the analytic process. Freud's views, expressed in his formulation, coincide with ideas that the author has put forward over the past two decades in regard to the vicious cycle of punitive unconscious self-criticism, self-deprivation, and excessive demand (narcissistic entitlement) and the need to maintain functional neutrality by providing support. The discussion addresses the contrast between Freud's therapeutic activity and his published recommendations, emphasising Freud's mistaken belief in the analyst's 'objectivity' in the analytic situation and his passionate commitment to maintaining the scientific respectability of psychoanalysis, with its consequences in the minimalist austerity of 'classical technique'. PMID- 7989138 TI - Species and strain comparisons of immunosuppression by 2-methoxyethanol and 2 methoxyacetic acid. AB - 2-Methoxyethanol (ME) and its principal metabolite 2-methoxyacetic acid (MAA) have been shown in our laboratory to be immunosuppressive in male Fischer 344 rats. In this study several strains of 12-week-old female rats and mice were used to compare the immunosuppressive activity of equimolar concentrations of ME and MAA on the trinitrophenyl-lipopolysaccharide (TNP-LPS) antibody plaque-forming cell (PFC) response, which we previously demonstrated to be a sensitive end point. Female inbred Lewis, Fischer 344 and Wistar/Furth, and outbred Sprague Dawley rats were dosed by gavage with either ME or MAA at dosages of 0.33 to 2.64 mmol/kg/day for 10 consecutive days. Female inbred C3H and C57BL/6J, hybrid B6C3F1, and outbred CD-1 mice were similarly dosed with equimolar dosages of 0.66 to 5.28 mmol/kg/day ME or MAA. All animals were immunized on day 9 of dosing and PFC responses evaluated 3 days later. Suppression of the PFC response was observed in all strains of rats at 2.64 mmol/kg/day ME or MAA. Lewis and Wistar/Furth rats were found to be the most sensitive strains with suppression at levels as low as 0.66 mmol/kg/day ME or MAA. While ME and MAA dosing resulted in suppression of the TNP PFC response in all the rat strains tested, such treatment did not suppress this PFC response in any of the mouse strains examined. These results indicate that under the conditions of this study rats, but not mice, are immunosuppressed by ME and MAA exposure, and that the susceptibility to immunosuppression differs among rat strains. PMID- 7989140 TI - The analyst's participation in the analytic process. AB - The analyst's moment-to-moment participation in the analytic process is inevitably and simultaneously determined by at least three sets of considerations. These are: (1) the application of proper analytic technique; (2) the analyst's personally-motivated responses to the patient and/or the analysis; (3) the analyst's use of him or herself to actualise, via fantasy, feeling or action, some aspect of the patient's conflicts, fantasies or internal object relationships. This formulation has relevance to our view of actualisation and enactment in the analytic process and to our understanding of a series of related issues that are fundamental to our theory of technique. These include the dialectical relationships that exist between insight and action, interpretation and suggestion, empathy and countertransference, and abstinence and gratification. In raising these issues, I do not seek to encourage or endorse wild analysis, the attempt to supply patients with 'corrective emotional experiences' or a rationalisation for acting out one's countertransferences. Rather, it is my hope that if we can better appreciate and describe these important dimensions of the analytic encounter, we can be better prepared to recognise, understand and interpret the continual streams of actualisation and enactment that are embedded in the analytic process. A deeper appreciation of the nature of the analyst's participation in the analytic process and the dimensions of the analytic process to which that participation gives rise may offer us a limited, although important, safeguard against analytic impasse. PMID- 7989141 TI - The value of the historical perspective to contemporary psychoanalysis: Freud's 'seduction hypothesis'. AB - In this paper the authors re-examine the development of Freud's ideas on seduction, with a special focus on the evidence which Freud presented and upon which he relied as he attempted to confirm these ideas. Through this re examination Freud's struggle with seductiveness, both in relation to his patients and in relation to his theories, comes to the fore. While the wish to be with the other through exerting an influence over him or her is perverted in the act of sexual seduction, it is, nevertheless, a force that must be recognised and contended with in other creative interchanges, including the analytic one. In studying Freud's struggle with this force, there is attained a better appreciation of the humanness, including the inevitable human limitations, of Freud and his thinking that rest at the foundation of psychoanalysis. This study thus has clear implications for the history of psychoanalysis, but, more importantly, it reveals the value for contemporary psychoanalysis in recognising this history. PMID- 7989143 TI - Abstinence and neutrality: development and diverse views. AB - Usually, Freud adopted a technical device for personal or practical reasons and only later formulated its theoretical basis. His conception of abstinence initially seemed designed to curb his own troublesome erotic countertransference. These speculations, while having no bearing on the clinical value of abstinence and related neutrality, do emphasise the necessity to assess their utility objectively, on the basis of clinical data. Diverse views of abstinence and neutrality persist in part because early inconsistencies in Freud's conceptions remain unresolved, and in part because these views are derived from the analyst's personality and character, are not based upon clinical data, but are buttressed by iteration. An approach to empirical assessment is suggested using multiple analyst-observers: (1) to develop reliable criteria for four analyst behaviours: abstinence, neutrality, gratification and suggestion; and (2) to evaluate enhancement or impairment of analytic work. Utilisation of this approach in the supervision of candidates would enhance analytic pedagogy and to some degree facilitate a research orientation in candidates. PMID- 7989142 TI - Interpretation and creationism. AB - This paper is an attempt to raise questions about certain underlying and implicit assumptions in some hermeneutic and narrative approaches to psychoanalysis. Starting from the view that Freud saw interpretation in the clinical setting as an attempt to unveil the analysand's psychic reality, it is argued that he envisaged that psychoanalysis aims to interpret what is real in the analysand's inner world--an empirical line of thought underpinned by the idea of analytic neutrality and an emphasis on the analysand's capacity to judge reality. By contrast, the tendency within the hermeneutic-narrative tradition is to demote psychic reality in favour of an emphasis on the analyst's capacity to interpret in order to help his analysand construct meaning. This approach may be said to put the analyst's words in the place of those of the Creator; in other words, it amounts to a 'verbal creationism', which the author argues is rooted in the idealistic philosophy of Hegel, Vico and Descartes and, further back, can be traced to the Book of Genesis--a conclusion causing the author to express some reservations. PMID- 7989144 TI - A classic revisited: Kurt Eissler's 'the effect of the structure of the ego on psychoanalytic technique'. AB - Eissler's influential contribution, which introduced the idea of the parameter of technique, extended Freud's later contributions so that they would apply to thoughtful analytic work with hard-to-treat patients. Aimed at sharpening the baseline of psychoanalytic technique-interpretation--and differentiating ego psychological work from Franz Alexander's modifications in particular, Eissler's 'parameter' was progressively and perversely made into a coercive, if not punitive, concept. Looking back on it now, one can see that, in addition to its merits, the paper advocates an orientation that is no longer beyond dispute. In contrast to the present pluralistic state of psychoanalytic approaches to treatment, certain aspects of Eissler's paper seem unacceptably finalistic, restrictive and uncritically committed both to assumptions about continua in development and pathological states and to an operational approach to diagnosis. PMID- 7989146 TI - Psychoanalysis as a lifeline: a clinical study of a transference perversion. AB - Case material from the analysis of a fetishistic cross-dresser is reported. The evolution of a transference perversion and treatment impasse, in the form of the recalcitrant symptom of anal flatulence, is described. The patient's contrasting needs to cling perversely and addictively to the analyst, on the one hand, and to provoke an acting out of the countertransference, on the other, are placed in the context of his dread of rejection and potentially suicidal reaction. The author argues in favour of offering psychoanalysis as a lifeline, but with the condition that the psychoanalytic setting and boundaries are maintained and that gratifications are denied. Limited but precise interpretive psychoanalytic work in the transference was maintained. The relatively good outcome is explained in terms of the provision of safety, survival of the analyst and avoidance of countertransference acting out, which, in the author's view, represents an implicit and mutative transference interpretation, the specific factor in bringing about psychic change. This enabled the patient to recognise and accept the analyst as a 'new' object and, as a consequence, to question and reject his idealisation of the anal universe that he inhabited. PMID- 7989145 TI - The man with the bus symptom. AB - This paper attempts to illustrate the clinical and technical vicissitudes of the psychoanalytic treatment of an adult male patient whose psychopathology alternated between a relatively stable phobic-obsessional structure and a perverse structure. The latter appeared in his life paroxysmally and took the form of riding the buses, when he would engage in various furtive sexual practices with small and adolescent girls. Both psychopathological structures were, of course, manifested in the relationship with the analyst. The description of their interplay in the transference-countertransference and of their relationship with the patient's life history makes up the first part of the paper. The gradual establishment of the perverse acting out in the therapeutic link led to a distortion of the setting which threatened the continuity of the analytic process, giving rise to a pragmatic paradox. This establishment of acting out in violation of the setting, coupled with recourse to the technique of reformulation of the setting, constitutes the main focus of this paper. The significant changes which ensued in the analytic process after this reformulation are then examined. PMID- 7989147 TI - Interpretations in projection. AB - The author uses the term 'interpretations in projection' to denote a form of interpretation which the analyst can use in extreme situations when he feels that he can no longer get through to his patient. This technique is particularly indicated with patients who resort to massive projective identification. The aim of interpretation in projection is to allow the patient to rediscover the bond of identity with the part of himself projected into the analyst. It falls into two stages, in the first of which the analyst becomes the spokesman for the 'healthy' part which the patient has projected into the analyst so as to protect it from the invading introjected object with which it is for the time being merged. In a second stage, the analyst may, where appropriate, give a complementary interpretation in which he addresses the analysand by his own name in order to interpret the relationship expressed in the transference through projection and introjection. The author gives some clinical examples of interpretations in projection. PMID- 7989148 TI - Borderline disorders: report on the 4th IPA Research Conference. PMID- 7989149 TI - Panel report. Special half-day programme on research: psychoanalysis and cognition. PMID- 7989150 TI - The intolerance of diversity in psychoanalytic institutes. AB - Psychoanalytic institutes, as well as other psychoanalytic organisations, historically have been prone to schisms. This paper attempts to seek out the causes for this institutional fragility in an examination of the kinds of anxiety for which these institutions provide--and ultimately often fail to provide- containment. Intolerance of diversity at one end of the spectrum and schism at the other are seen as social defences against often unrecognised forms of anxiety associated with the practice of psychoanalysis. One source of anxiety, arising from the isolation of psychoanalytic work, derives from the contradiction between the analyst's need to belong to a particular school and his need to believe he is fully receptive to the clinical material of his patient. A second source of anxiety derives from the contradiction between his membership in his organizations and his affiliations to the various pairs within which the primary work of psychoanalysis takes place. A third source of anxiety derives from his participation in the culture of psychoanalysis, which sees itself as apart from the world of social reality; psychoanalysts, as a result, devalue and fear the very institutions that connect them with that world. PMID- 7989151 TI - The ambivalence of the maternal body: psychoanalytic readings of the legend of Van Gogh. AB - This article aims to identify the collective social investment in 'Van Gogh' as a cultural icon, and to ask what function his life story, colourfully illustrated by his art work, has performed in the West since the 1890s. It argues that the life and work of a Dutch artist have become the raw materials for a series of secular 'mystery' plays and christological psychodramas that reflect the ills of twentieth-century experience. The key moments when Van Gogh was made into a figure in a popular imagination were psychologically significant: the Depression and the immediate aftermath of World War II. 'Van Gogh', a fantasy figure of modern man, has been over-'psychologised', his work becoming only the testament to the myth of modern man. Using social-art-historical techniques, the author tries to distance this kind of reading in the case of one drawing of a peasant woman, bending over. Situating the fantasy that the drawing services in precise social and historical terms of bourgeois men formed in childhood in relation to a split feminine/maternal figure of the lady/mother and the working-class nursemaid, the article examines how to use psychoanalysis to read the formal oddities of the work--distortion and monumentality, attention to a fragmented, eroticised but also punished body--for the oscillation between pre-oedipal fantasies of maternal plenitude and awe and oedipal anxieties which sadistically inflict humiliation on the maternal body. Finally, instead of producing Van Gogh as the extreme case of an 'other', the author recognises the drawing as a space where present fantasies of the reader encounter those of the producer. Psychoanalysis informing historically-precise interpretation becomes a demythologising hermeneutic. PMID- 7989152 TI - Freud, Sellin and the death of Moses. AB - An examination of the actual arguments put forth by the Biblical scholar Ernst Sellin regarding the hypothesis of the murder of Moses, upon which Freud is supposed to have based his own analysis in 'Moses and Monotheism', reveals that Sellin's theory, which differs widely from Freud's, contains many features which ought perhaps to have appealed to Freud, most notably, the depiction of the deed as a graphic scene of oedipal violence and primal scene imagery. In exploring why Freud might have chosen not to use Sellin's reconstruction of the death of Moses, the author proposes that his version allowed, as Sellin's did not, for an analogy between Israelite history and the typical course of an obsessive-compulsive neurosis; and that the value of the latter lay in its providing grounds for hope that psychoanalysis itself might survive a period of 'latency' in the wake of Freud's impending death. In addition to speculating about Freud's motives, the author seeks to give a good exposition of Sellin's ideas, which despite their importance to Freud's thought remain relatively unknown or misunderstood in psychoanalytic circles. PMID- 7989153 TI - Hans W. Loewald, M.D. (1906-1993). PMID- 7989154 TI - What is psychoanalysis now? PMID- 7989155 TI - Do autistics have a generalized face processing deficit? AB - The study presents results from a clinical test battery (Bruyer & Schweich, 1991; Schweich & Bruyer, 1993) that is used to study components in the face recognition system of autistic children. The results of the autistics are compared with the performance of two age groups of normal children (7-10 years, 12-16 years) and an adult control group. Autistic subjects, like young children, make more errors on a task in which they have to match facial features in the context of a complete face but not when the features are presented in isolation or in a simplified facial context. Finally, the sensitivity of the battery for clinical populations other than prosopagnosics is discussed. PMID- 7989156 TI - Validity and clinical utility of sleep laboratory criteria for insomnia. AB - The sensitivity, specificity, and positive predictive value of two proposed sleep laboratory criteria for the diagnosis of insomnia were evaluated in 375 adults with a primary complaint of insomnia and 150 noninsomniac controls. The two criteria used results in either low sensitivity and moderately strong specificity or high sensitivity and low specificity and, accordingly, in both cases weak positive predictive values (diagnostic accuracy), both for one night and multiple nights of recordings. Further, an empirically optimized criterion also resulted in an unsatisfactory diagnostic accuracy. Finally, the optimized MMPI criteria were superior to optimized sleep criteria in differentiating insomniacs from controls. In conclusion, sleep laboratory recordings provide little relevant information for confirming or excluding the presence of insomnia. PMID- 7989157 TI - Immunological fluctuations during intrathecal immunotherapy in three patients affected by CNS tumours disseminating via CSF. AB - The immunological therapy of cancer has been proposed in a number of neoplasms (Borden, Sondel, 1989; Foon, 1989; Rosenberg, 1992) and has recently been adopted in the treatment of Central Nervous System (CNS) tumors in combination with conventional surgical and radiotherapeutical approach. In this context, loco regional administration of immunomodulating agents (for instance in post-surgical cavity) allows to achieve much higher in situ concentrations than by systemic route. Since these treatments have potential adverse effects, careful assessment of clinical and immunological parameters in phase I trials is needed. CNS tumors disseminating via Cerebrospinal Fluid (CSF) pathways offer a stimulating opportunity for intrathecal immunotherapy. In this context, alpha-IFN and IL2 (alone or in combination with LAK cells) have been employed either loco regionally or intrathecally (Merchant, Mc Vicar, Merchant & Young, 1992; Schiller, Hank, Storer, Borchert, Moore, Albertini, Bechhofer, Wesley, Brown, Bastin & Sondel, 1993). The rationale for the use of both these substances includes the known anti-tumor action of alpha-IFN (Mahaley, Urso, Whaley, Blue, Williams, Guaspari & Selker, 1985; Nagai, 1988) and the ability of r-IL2 to generate activated cells effective in lysing tumor cell targets (Hayes, Moore, Pierz, Chen, Da Rosso, Nirenberg & Allen, 1993). We treated 3 patients (2 affected by disseminating cerebellar medulloblastoma, 1 by disseminating thalamic glioblastoma) by intrathecal r-IL2 via recervoir. In the first 2 patients, this treatment was preceded by alpha-IFN (also intrathecally). Monitoring of immunological effects of the treatment schedule involved kinetics of CSF and serum TNF-alpha, IL2s and IL2R during the first day of r-IL2 treatment, as well as on day +2 and +4 of both r-IL2 cycles, and assessment of CSF cells, protein and CSF and PB NK cell activity and CD3-CD56+ cells during the course of all treatment cycles. We also assessed clinical and neuroradiological effects of immunotherapy. PMID- 7989158 TI - Behaviorally conditioned modulation of natural killer cell activity: effects of pre-conditioning manual restraint and apparatus exposure. AB - This study investigated behaviorally conditioned modulation of natural killer cell (NK) activity. One and three trial behavioral conditioning training trial designs were examined. In addition, the influence of pre-conditioning exposure to manual restraint and the conditioning apparatus upon behaviorally conditioned natural killer cell responses was assessed. Prior to one trial training, animals were exposed to either the conditioning apparatus, manual restraint, or were undisturbed. The animals were then trained to associate the conditioned stimulus (CS) and the unconditioned stimulus (US), and later re-presented with the CS. Behaviorally conditioned animals demonstrated significantly enhanced NK cell activity, no difference in NK activity, or significantly decreased NK activity, respectively. There was also a significant interaction between the manual restraint and behavioral conditioning interventions. Animals in a three training trial design were either manually restrained daily prior to and during behavioral conditioning or were left undisturbed. In this design behavioral conditioning significantly decreased NK cell activity and manual restraint significantly increased NK cell lytic activity. These data illustrate behaviorally conditioned decreases and increases in NK cell lytic activity dependant upon the experimental design. Behaviorally conditioned NK cell activity is influenced by additional behavioral interventions (i.e. manual restraint and novelty of conditioning environment) inherent within the behavioral conditioning procedures. PMID- 7989159 TI - Improvement in word-fluency performance in Parkinson's disease by administration of electromagnetic fields. AB - The association between degeneration of the nigrostriatal dopamine (DA) system and the motor manifestations of Parkinson's disease (PD) provided the impetus for the development of DA replacement therapy. However, clinical experience has demonstrated that DA-ergic drugs, while attenuating the motor symptoms of PD, have little or no consistent effect on the mental and cognitive symptoms of the disease which are thought to be related partly to degeneration of the meso cortico-limbic DA system. Thus, failure of DA-ergic drugs to improve the mental and cognitive deficits of PD indicates that these agents cannot fully restore DA functions in the meso-cortico-limbic circuits. The present communication concerns five fully medicated Parkinsonian patients in whom application of a series of treatments with electromagnetic fields (EMF) of extremely low intensity (in the picotesla range) and frequency (5-8Hz) produced a dramatic improvement in performance on Thurstone's World-Fluency Test, a sensitive marker of frontal lobe functions. These findings suggest that in contrast to DA replacement therapy application of low intensity EMF may improve frontal lobe functions in patients with PD presumably by augmenting DA activity in the mesocortical system. As deficiency of the frontal DA system has been implicated also in the development of akinesia and freezing in PD these observations may explain the beneficial effects of EMF on the motor manifestations of the disease. PMID- 7989160 TI - Ambilaterality: definition from handedness preference questionnaires and potential significance. AB - Defining handedness according to the results of preference questionnaires is operational. Most often, handedness is defined according to the extremes of the handedness range or equal divisions of the entire handedness range. These definitions may exclude ambilateral (ambidextrous) subjects from analysis or may fail to separate out subjects with intermediate handedness scores. Examples from the literature are presented to show that subjects with handedness scores in the weak right-handedness range may have characteristics that distinguish them from subjects in other segments of the handedness spectrum. Handedness studies should assess the middle handedness range using a scoring method which identifies subjects in this range. PMID- 7989161 TI - Developmental changes of pyroglutamate-peptidase I activity in several regions of the female and the male rat brain. AB - In this work, we have described decreases of pGlu-peptidase I activity, detected using pGlu-beta-naphtylamide as substrate, from 9 to the 20 days after birth in five brain areas. In addition, we have found sexual differences in the enzyme activity in the hypothalamic-pituitary axis in all ages investigated. pGlu peptidase cleaves the pGlu-aminoacid bond of several neuropeptides such as thyroliberin, luliberin and neurotensin. The decrease in the activity of pGlu peptidase coincidents with the increases observed in brain thyroliberin concentration and the decreases in His-Pro diketopiperazine. It is suggested that this enzyme could play a part in the normal development of the rat brain. PMID- 7989162 TI - A cognitive-neuroscience approach for elucidation of mechanisms underlying temporal information processing. AB - Temporal processing of durations in the range of seconds or more is cognitively mediated, whereas processing of brief durations below 100 ms appears to be based on brain mechanisms beyond cognitive control. In a series of experiments, applying a single-behavior-multiple-brain-systems strategy, activity of various neurotransmitter systems was pharmacologically changed and effects on temporal information processing were studied. In addition, concomitant changes in different psychological functions, such as cortical arousal, speed of information processing, and memory were measured. This experimental strategy proved to be highly efficient for elucidating mechanisms underlying temporal information processing in humans. Temporal processing of durations in the range of seconds was markedly impaired by pharmacologic agents which induced deterioration of memory functions. On the other hand, temporal processing of brief durations below 100 ms was shown to be largely independent of pharmacologically induced impairment of cognitive functioning, but may rather depend on D2 receptor activity in the basal ganglia. PMID- 7989163 TI - Reversal of micrographia in Parkinson's disease by application of picoTesla range magnetic fields. AB - Micrographia, a common and often early sign of Parkinson's disease (PD), is a sensitive clinical marker of the severity of bradykinesia and rigidity in the disease. As micrographia may be reversed by treatment with dopaminergic drugs and may emerge during therapy with neuroleptic agents, it is thought to reflect striatal dopaminergic deficiency. It has been reported recently that external application of picoTesla range magnetic fields (MF) produced a dramatic improvement in the motor symptoms of PD suggesting that these weak MF enhance striatal dopaminergic neurotransmission. In the present communication, we present a 61 year old patient with PD in whom picoTesla range MF attenuated the severity of bradykinesia and rigidity, improved postural stability, and rapidly reversed the micrographia within 30 minutes after termination of treatment. In contrast, sham (placebo) MF did not influence the severity of the motor symptoms of the disease or the associated micrographia. This report demonstrates the antiParkinsonian effect of picoTesla range MF and highlights the unique efficacy of these weak MF in the therapy of Parkinsonism. PMID- 7989164 TI - Stephen Walter Ranson (1880-1942): a pioneer in hypothalamic research. PMID- 7989165 TI - Electroencephalographic cartography of conscious states. AB - We analyzed monopolar recordings obtained from a brain area implicated in the implementation of conscious intention--the Supplementary Motor Area. Other monopolar recordings were taken at F3, F4, C3, C4, P3, P4, O1, O2, F7, F8, T3, T4, T5, T6, and Cz using the standard international (10/20) pattern with linked ears as reference. Using on line fast-fourier transforms of brainwave signals and computer displays with one-second updates of 1Hz wide brainwave bands of 5, 7, 10, 12, 14, 16, 20 and 28 Hz, specific brainwave signatures were identified for attentional, cognitive, imaginal, and somatosensory states. This first, and thus limited, cartography of consciousness is discussed in light of the cognitive descriptions clinically ascribed to the commonly used brainwave frequency bands designated as Delta, Theta, Alpha, and Beta. PMID- 7989166 TI - Visual cortical neuron responses to drifting sine-wave gratings in rabbits. AB - Neurons of area 17 (V1) in rabbits were stimulated with drifting sine-wave gratings. Animals were anesthetized and paralyzed under conventional methods to record action potentials of single cells using tungsten-in-glass micro electrodes. Neurons responded in modulatory or unmodulatory patterns depending on whether cells were of the simple or complex type, respectively. In the spatial domain, most cells were Low-Pass and Band-Pass, with no recordings of High-Pass units. In the temporal domain, Low-Pass, Band-Pass and High-Pass behaviours were found. Rabbits appeared to exhibit all types of pattern responses found in other foveate mammals, including special-complex and end-stopping units. However, in the majority of cells, there was a shift towards the lower end of the spatial frequency spectrum. For instance, the optimal spatial frequency was in the vicinity of lc/d while in the temporal domain, some units responded optimally at 10 c/s. In conclusion, it appears that rabbit cortex contain neurons which are selective for spatial frequency in a manner comparable to that seen in cat and monkey. PMID- 7989167 TI - Project 2000 and the replacement of the traditional student workforce. AB - This paper reports on part of a 4-year study monitoring the implementation of Project 2000 in one health authority. Its focus is on the consequences for the nursing service of replacing traditional, pre-Project 2000 students with permanent staff. It is argued that the Department of Health, who have been responsible for funding the replacement programme, have underestimated the numbers of permanent staff required to replace the traditional student workforce, and that the Project 2000 replacement exercise has contributed to a deterioration in staffing levels and skill mix. PMID- 7989168 TI - Some factors associated with change in patient-centredness of student nurses during the Common Foundation Programme in Nursing. AB - This longitudinal study examines the changes in patient-centredness of a group of student nurses during their Common Foundation Programme in Nursing, and attempts to explore some of the social, psychological and educational factors which might be associated with such change. The Patient-centredness Multi-choice Questionnaire (PMQX) was administered to a sample of 267 student nurses on commencement and completion of their Common Foundation Programme in Nursing, and significant positive as well as negative changes in PMQX scores were found, although the mean scores for the sample were unchanged. A number of factors were found to be associated with high levels of patient-centredness on commencement of the course, including marital status, age, and radicalism. Positive change in patient-centredness during the CFP was associated with a variety of variables such as class size, a student-centred climate and a tenderminded attitude. Other factors, such as psychological stability and extroversion, were associated with both increase and decrease in patient-centredness during the CFP. PMID- 7989169 TI - Learning styles of students: development of an eclectic model. AB - Many researchers have hypothesised that people have an affinity with one of two broadly opposite styles of learning. This paper uses a mainly psychological perspective to examine some teaching and learning styles. Much research into learning styles exhibits original and imaginative approaches to the issues identified by learners and educators, however there is also a degree of recycling of concepts. This paper reports the development of an eclectic model of learning styles designed by considering various concepts, from which four major bipolar theories are refined in the light of sources to identify the core concepts. The selections and exclusions made in the model-building may precipitate dispute. Robust debate is invited, though the eclectic model as it now stands may be thought to offer a serviceable framework for enhancing the sensitivity of nurse educators to students' individuality expressed in their learning styles. How the variety in students' learning styles can be addressed by differing teaching/learning strategies is also discussed. It is concluded that nurse education should strive to move towards matching teaching to learning styles. PMID- 7989170 TI - Relationships in health visiting: enabling and mediating. AB - During a grounded theory study into health visiting the role of the relationship with clients was uncovered. It was found that they have a necessary enabling and mediating function for health visitors' work. Although the literature has highlighted the importance of the relationships in health visiting, the work involved in building them has been taken for granted. It is hoped that it will be considered when appraising health visitors' work. PMID- 7989171 TI - Nursing shortages and human resource planning. AB - This paper takes a broad based international perspective in examining the issue of nursing shortages. The role of human resource planning is discussed, and policy interventions to prevent shortages or ameliorate their effects are assessed and recommendations for action are made. The paper draws on published research from a number of countries and identifies key issues common to all countries. PMID- 7989172 TI - Self-efficacy: a means of identifying problems in nursing education and career progress. AB - Two nursing self-efficacy scales (academic and clinical) were developed and refined for use in identifying problems in progress in undergraduate nurses. Emergent factors within each scale contained items representing important aspects of nursing education. Both measures showed good internal consistency, test-retest reliability, and construct validity. Sensitivity to content and focus of tuition at time of completion was shown with some changes in factor structure over samples of first year nursing students. Academic self-efficacy (but not clinical self-efficacy) was predictive of course withdrawal. Applications to nursing education, progress in pursuing a nursing career and attrition are discussed. PMID- 7989173 TI - Cross-cultural beliefs about "depression". AB - This study set out to compare native Britons' and Asian-Britons' (from the Indian sub-continent) beliefs about the causes and cures of depression. In all 152 females took part, half of whom were middle-aged and half young. The results indicated that middle-aged Asian migrants significantly differed from the middle aged British and young Asian samples in their beliefs about depression and anti depressive behaviour. They also scored significantly higher than the middle-aged British women on a Western measure of psychiatric morbidity, yet they did not report depression in themselves or others. The young Asian sample, on the other hand, appear to have adopted a perception of depression that is similar to that of their British peers. It seems that the perception of the causes and symptoms of depression and appropriate anti-depressive behaviour is mediated by cultural values and beliefs that the individual has been exposed to in their formative years, which subsequently affects their tendency to recognise, report and seek help for depression. The results are discussed in terms of the literature on the 'new cross-cultural psychiatry'. PMID- 7989174 TI - Religious identity and comfort beliefs in three groups of psychiatric patients and a group of medical controls. AB - In order to assess the religious beliefs and practices of psychiatric patients, a self-report questionnaire was developed. The questionnaire was administered to 73 psychiatric patients and 25 non-psychiatric controls. Older age, membership of an ethnic minority and the presence of psychiatric disorder were all significantly associated with higher scores on the questionnaire. Psychotic subjects obtained the highest scores whilst those of depressed and parasuicide subjects were intermediate between those of the control and the psychotic groups. These results emphasise the importance of religion for many patients with common psychiatric problems. Specialist religious help may be of value in the management of such problems. PMID- 7989175 TI - Homeless women, disaffiliation and social agencies. AB - Homeless individuals have limited social support systems. Not clearly defined, however, is the relationship between homelessness, gender, and social agencies. In our study 102 homeless individuals were interviewed in shelters. This included administration of the SADS and the subject's rating their perceived level of support from friends, family and social agencies. Significant findings in the analysis showed a higher level of perceived support by males than by females (p < 0.05). More precisely, this was true in the area of support from social agencies, where females rated support from these organizations as significantly lower than did males (p < 0.05). The findings were unchanged when age, presence of psychiatric illness or length of time homeless were factored in. Important implications for public policy are clear since existing social service agencies working with the homeless are less likely to be perceived as supportive by females than by males. PMID- 7989176 TI - Predictors of employment status of treated patients with DSM-III-R diagnosis. Can logistic regression model find a solution? AB - To investigate the predictors of employment status of patients with DSM-III-R diagnosis, 55 patients were selected by a simple random technique from the main psychiatric clinic in Al Ain, United Arab Emirates. Structured and formal assessments were carried out to extract the potential predictors of outcome of schizophrenia. Logistic regression model revealed that being married, absence of schizoid personality, free or with minimum symptoms of the illness, later age of onset, and higher educational attainment were the most significant predictors of employment outcome. The implications of the results of this study are discussed in the text. PMID- 7989177 TI - Case report: F23. AB - In this paper, we draw attention to the advantage of the International Classification of Diseases 10th Edition in the classification of short lived, reactive, psychotic illnesses over other systems of classification in widespread use, and illustrate this with some case histories. PMID- 7989178 TI - The social and biological components of mental disorder: implications for services. The 1993 Joshua Bierer Memorial Lecture. PMID- 7989179 TI - The importance of choice. PMID- 7989180 TI - Zero tolerance for violence. PMID- 7989181 TI - Don't shoot the messenger. PMID- 7989182 TI - Managed care contracting: a road map around potholes. PMID- 7989183 TI - Preparing for capitation. PMID- 7989184 TI - Leptospirosis: a consequence of the Iowa flood. PMID- 7989185 TI - Monitoring of 222Rn in Taiwanese hot spring spa waters using a modified electret ion chamber method. AB - 222Rn concentrations in some Taiwanese hot spring spa waters have been monitored using commercially available electret ion chambers (EIC). The use of two EIC units for measuring radon concentrations in the air phase and voltage dependent correction factors for subtracting gamma contributions resulted in improved accuracy. PMID- 7989186 TI - Electret method for continuous measurement of the concentration of radon in water. AB - A passive system using an electret ion chamber to measure dissolved radon in a water sample has been recently described. In the current work, an electret ion chamber has been used to measure time-averaged concentration of dissolved radon in water. A steady concentration of radon in water is generated by bubbling radon gas into water in a 20-L jar and maintaining constant rates of feed and bleed of the water. To perform the measurement, the outgoing water flows into a 4-L cylindrical chamber. Air is bubbled at 1 L min-1 through a 10 cm long sintered stainless steel tube immersed in this water releasing the radon from water into the chamber volume. A 1-L electret ion chamber ("H" chamber) loaded with an electret is hung in the 4-L chamber. Radon diffuses into the "H" chamber through its tyvek (carbon-coated) covered openings. The radon concentration in air is measured from the change in electret voltage. The concentration of radon in water is then obtained from the concentration of radon in air and the air and water flow rates. For comparison, the radon concentration in water was measured using a standard liquid scintillation counting method. For the concentration range covered (4.7 to 72 Bq L-1), there was a good agreement between the two methods. PMID- 7989187 TI - The International Committee for Radionuclide Metrology. PMID- 7989188 TI - Substitution of di-octyl phthalate in HEPA filter testing. PMID- 7989189 TI - "The societal obligation of health physicists:" the Landauer 40th Anniversary Lecture. PMID- 7989190 TI - Return to normality after a radiological emergency. AB - Some preliminary considerations from the management of post-accident situations connected to large scale and high land contamination are presented. The return to normal, or at least acceptable living conditions, as soon as reasonably achievable, and the prevention of the possible emergence of a post-accident crisis is of key importance. A scheme is proposed for understanding the dynamics of the various phases after an accident. An attempt is made to characterize some of the parameters driving the acceptability of post-accident situations. Strategies to return to normal living conditions in contaminated areas are considered. PMID- 7989191 TI - Radiation transport in a radiotherapy room. AB - The photoneutron dose equivalent in a linac radiotherapy room and its entrance maze was investigated by means of Monte Carlo simulations under different conditions. Particularly, the effect of neutron absorbers and moderator layers placed on the maze walls was considered. The contribution of prompt gamma rays emitted in absorption reactions of thermal neutrons was also taken into account. The simulation results are compared with some experimental measurements in the therapy room and in the maze. PMID- 7989192 TI - A double chamber system for producing constant radon concentration. AB - An experimental arrangement of a radon chamber with an intrinsic constancy of the relative radon concentration is described. The system consists of a reference chamber and an auxiliary storage chamber. The only active device is a timer controlled pump or valve which feeds radon gas from the storage into the reference chamber. The switching pattern of the timer is extracted from model calculations and theoretically performs an exact compensation of the radon loss by radioactive decay. If the calculations are done in real time and online, every known external event influencing the radon concentration can be compensated. This paper presents a simple timer circuit and a computer code which generates the timer program. The influence of the air flow stability and the leakage of the chambers are discussed. It is planned to apply this theoretical approach to provide a constant radon gas concentration for an actual chamber. PMID- 7989193 TI - Alpha radiation risk coefficients for liver cancer, bone sarcomas, and leukemia. AB - This study compares published risk coefficients with those determined from dose rates established by postmortem radiochemical analysis of tissues from two whole body donors to the U. S. Transuranium and Uranium Registries, both of whom had been injected with Thorotrast approximately four decades prior to death. The dose data from these cases were used in combination with published latent periods and epidemiologic study results to calculate the following risk coefficients: 0.020 liver cancers Gy-1, 0.002 bone sarcomas Gy-1, and 0.032 leukemias Gy-1. These compare with the ranges of 0.013 to 0.074 liver cancers Gy-1, 0.0016 to 0.0120 bone sarcomas Gy-1, and 0.005 to 0.060 leukemias Gy-1 reported in the literature. The results of this study are generally consistent with previously reported values with two exceptions: the values for bone sarcomas fall below the range given by BEIR IV and the values for leukemia are a factor of 6 greater than those reported by BEIR IV. This suggests that the BEIR IV risk coefficient for bone sarcomas may be too high, and that for leukemia may be too low. PMID- 7989194 TI - Issues in space radiation protection: galactic cosmic rays. AB - When shielding from cosmic heavy ions, one is faced with limited knowledge about the physical properties and biological responses of these radiations. Herein, the current status of space shielding technology and its impact on radiation health is discussed in terms of conventional protection practice and a test biological response model. The impact of biological response on optimum materials selection for cosmic ray shielding is presented in terms of the transmission characteristics of the shield material. Although liquid hydrogen is an optimum shield material, evaluation of the effectiveness of polymeric structural materials must await improvement in our knowledge of both the biological response and the nuclear processes. PMID- 7989195 TI - Occupational exposure and its effect on some immune parameters. AB - Some immunological parameters were investigated in a group of workers exposed to external radiation (1.4 to 9.8 mSv) and inhalation of tritium (comm. eff. dose equiv. 1.2 to 2.8 mSv). The present investigations indicate the differential radiosensitivity of lymphocytic subsets: CD8 positive suppressor T cells were found to be the most sensitive subpopulation in the peripheral blood of radiation exposed workers. CD4/CD8 ratios were increased mainly due to an increase in absolute numbers of CD4 positive helper T cells indicating a selective cell renewal after irradiation. Results obtained after phytohaemugglutinin stimulation of lymphocytes showed individual variation, though there seems to be a trend towards an inverse correlation between absolute T cell numbers in peripheral blood and the number of S phases observed after stimulation, low T cell numbers leading to a high rate of stimulation. The calculation of the committed effective dose equivalents show that radiation protection against internal tritium contamination in power plants should not be neglected. PMID- 7989196 TI - Health physics: a personal history. PMID- 7989197 TI - Effect of modified calm conditions on nuclear dispersion estimates. AB - When the definition of calm in atmospheric diffusion analyses is changed from 0.5 m s-1 to 0.1 m s-1, actual and more accurate low wind speeds and wind directions can be used to calculate the average air concentrations due to continuous releases of radionuclides at 10-m stack height more realistically and accurately. However, this modified calm condition has little affect on the calculated adult thyroid exposure for a postulated accident. PMID- 7989198 TI - Electric field and current density distributions induced in an anatomically-based model of the human head by magnetic fields from a hair dryer. AB - We have used the impedance method to calculate the induced electric (E) fields and current densities (J) for the spatially varying vector magnetic fields due to a hair dryer. In this method, applicable for low-frequency exposures where the quasi-static approximation may be made, the biological body or the exposed parts thereof are represented by a three-dimensional (3-D) network of impedances whose individual values are obtained from the electrical properties sigma, epsilon r for the various tissues. We have measured the 3-D variations of the 50-Hz magnetic fields from a typical hair dryer and found that the various components correlate well with those for a helical coil. The non-uniform magnetic fields thus obtained are used to calculate the induced E and J with a resolution of 1.31 cm for the model of the head and neck. The induced E values are compared with the fields endogenous to the body and the minimum detectable E-field limits based on the cellular thermal noise model proposed by Weaver and Astumian (1990, 1992). PMID- 7989199 TI - Characteristics of the chemical forms of 11C, 13N, and 15O induced in air by the operation of a 100 MeV electron linear accelerator. AB - To characterize airborne radioactivity induced by the operation of high-energy accelerators, the fractions of aerosol and gaseous components, and the chemical forms of 11C, 13N, and 15O produced in the air of a target room of a 100 MeV electron linear accelerator were studied. Measurements of radioactivity using a particulate air sampling filter and a gas flow-through ionization chamber showed that more than 98% of 11C, 13N, and 15O were present as gaseous forms. Their chemical forms, detected by means of radio-gas chromatography, were 11C as CO2; 13N as N2 and NO; and 15O as O2 and NO. Machine operating conditions, which affect the compositions of the induced radionuclides and of their chemical forms, and the resulting effect on the estimation of internal doses are discussed. PMID- 7989200 TI - Residence times of global weapons testing fallout 237Np in a grassland soil compared to 239 + 240Pu, 241Am, and 137Cs. AB - The vertical distribution of weapons testing fallout 237Np has been determined in an undisturbed grassland soil (Alfisol). By using a compartmental model for multi layered soils, the mean residence half-times of 237Np in each soil layer were calculated and compared with results on weapons fallout 239 + 240Pu, 241Am and 137Cs in the same soil. The results show that the mobility of 237Np was in most soil horizons either equal or slightly enhanced as compared to that of Pu, Am, and radiocesium. PMID- 7989201 TI - A critical review of 55Fe dosimetric models. AB - The available literature on 55Fe dosimetry has been devoted to environmental exposures and medical iron kinetic studies. For occupational dosimetry, ICRP (1979, 1988) published a non-recycling dosimetric model for iron. These ICRP publications do not provide information on iron excretion. Johnson and Dunford (1985) published dose conversion factors and urinary excretion curves based on the ICRP (1980) and MIRD (1983) iron metabolic models. A critical review of these models was undertaken to select a model for occupational dose assignment. The review indicated that the information and recommendations in ICRP (1988) and Johnson and Dunford (1985) are dependent on unrealistic assumptions that do not agree with known iron metabolism. Therefore, an alternative model is proposed for dosimetric application. Calculations of dose conversion factors and urinary excretion curve for class W55Fe inhalation exposure (1 micron AMAD) using the proposed model are compared with predictions based on ICRP (1980) and Johnson and Dunford (1985) models. The difference in the practical outcome (i.e., dose assignment) is examined by applying the proposed and reviewed models to a realistic bioassay case. The Johnson and Dunford (1985) model yields a dose estimate which is roughly a factor of ten higher than values predicted by ICRP (1980) and the proposed model. Some of the disagreement is due to uncertainty in the fraction of radio-iron excretion via urine. Further research on this subject is recommended. In the interim, the proposed model is recommended for occupational dose assignment. PMID- 7989202 TI - Natural effective half-life of 137Cs in tea plants. AB - Contamination levels and variation of 137Cs in tea plant leaves from 1986-1992 were determined over the coast line of the Eastern Black Sea region in Turkey. The decrease of 137Cs radionuclide concentration in tea plant leaves may be described by a double exponential function with 94.8% activity lost with a Teff of 125 d and 5.2% activity lost with a Teff of 1,114 d. PMID- 7989203 TI - Intensive care, not intensive antibiotics. PMID- 7989204 TI - Antibiotic use and antibiotic resistance in the intensive care unit: are we curing or creating disease? AB - Antibiotics represent one of the most commonly prescribed medical therapies for hospitalized patients. The practice of "spiralling empiricism" has increasingly led to the unnecessary administration of antibiotics, resulting in the emergence of infections with antibiotic-resistant bacteria that are associated with increased rates of patient mortality. Ventilator-associated pneumonia due to antibiotic-resistant bacteria has become recognized as an important problem resulting from prior antibiotic exposure. Health professionals must be aware of this problem and avoid the unnecessary administration of these drugs. Future research efforts should be aimed at improving our ability to diagnose and exclude infections and to develop better strategies for antibiotic administration in the intensive care unit setting. PMID- 7989205 TI - Changes in oxygen saturation during weaning from short-term ventilator support after coronary artery bypass graft surgery. AB - OBJECTIVE: To evaluate changes in oxygenation as measured by pulse oximetry (SpO2) and saturated venous oxygenation (SvO2) during weaning from mechanical ventilator support. DESIGN: Exploratory, pilot study. SETTING: Cardiovascular intensive care unit in a private 691-bed acute care medical center in the South. SUBJECTS: Ten adults between 50 and 76 years of age who had uncomplicated coronary artery bypass graft surgery. OUTCOME MEASURES: SpO2 and SvO2 obtained at start of each weaning event and each minute for 5 minutes thereafter. METHOD: Five discrete events associated with the unit's weaning protocol were studied: ventilator adjustments, continuous positive airway pressure trial, respiratory mechanics, removing continuous positive airway pressure and suctioning, and extubation. Weaning events, initiated by unit staff members, were based on subjects' arterial blood gases, SpO2, respiratory rate, blood pressure, heart rate, level of alertness, and respiratory effort. RESULTS: Both SpO2 and SvO2 changed with weaning. For some subjects these changes were clinically important: SvO2 fell by 10% or more, and SpO2 fell to or below 90%. The assessment parameters guiding the weaning process resulted in some weaning events being initiated when SvO2 was at or below 60%. CONCLUSIONS: Measures of SpO2 and SvO2 are sensitive to changes in oxygenation status during weaning. Although more study is needed, SvO2 measures provide valid information about oxygen status and can be used to guide weaning. PMID- 7989206 TI - Thoracentesis in clinical practice. AB - Thoracentesis is a commonly performed procedure indicated for diagnostic and therapeutic purposes. Removal of pleural fluid should be performed by experienced operators and, when attempted by physicians-in-training, close supervision by credentialed individuals is necessary. Diagnostic thoracentesis is most valuable in separating exudates from transudates. Analysis of the exudative fluid has the highest yield when infection and malignancy is likely. Pneumothorax is the most common major complication and can be minimized by the use of small-gauge needles (no. 21 or no. 22) when a small amount of fluid is removed (35 to 50 ml). Patients who may pose difficulties (e.g., those receiving ventilator support) appear to have no greater morbidity with thoracentesis than those patients not ventilator dependent. Ultrasound may be of value to decrease morbidity when small or loculated volumes of fluid are present. Therapeutic thoracentesis offers relief of symptoms of dyspnea, but caution is particularly needed because large needles and large volumes of fluid removed may increase morbidity. PMID- 7989207 TI - A phenomenon of paradox: myocardial reperfusion injury. AB - Nurses who care for patients experiencing angina or myocardial infarction, receiving thrombolytics, and undergoing percutaneous transluminal coronary angioplasty or cardiac surgery should be aware of factors that contribute to myocardial reperfusion damage and dysfunction. This article reviews mechanisms identified as contributing to myocardial reperfusion injury. These include generation of oxygen free radicals, loss of antioxidant enzymes, neutrophil initiated damage, calcium abnormalities, loss of normal adenosine triphosphate concentration, myocardial stunning, vascular endothelial and myocyte edema, hemorrhage, and reperfusion arrhythmias. This article specifically focuses on the pathophysiology of myocardial reperfusion injury and important related research. PMID- 7989208 TI - Word descriptors in suspected acute myocardial infarction: a comparison between patients with and without confirmed myocardial infarction. AB - BACKGROUND: Acute myocardial infarction (AMI) will not develop in a large proportion of patients admitted to the coronary care unit because of suspected AMI. OBJECTIVE: To evaluate whether patients with confirmed AMI use different words to describe their pain than patients in whom AMI was not confirmed. DESIGN: A retrospective descriptive design. METHODS: The Pain-O-Meter, a verbal pain scale composed of 12 sensory and 10 emotional word descriptors, was used to assess pain. SETTING: Coronary care unit in Sahlgrenska Hospital in Goteborg, Sweden. SUBJECTS: A convenience sample of 889 consecutive patients admitted to the coronary care unit because of suspected AMI. RESULTS: SENSORY COMPONENT- patients with confirmed AMI differed from those without AMI in the use of the words "pricking" (12% vs 17%; p < 0.05) and "tearing" (11% vs 6%; p < 0.05). No difference was found in the remaining 10 words. Affective components--Patients with confirmed AMI differed from those without AMI in the use of "terrifying" (29% vs 18%; p < 0.001), "intolerable" (16% vs 10%; p < 0.01), and "worrying" (48% vs 59%; p < 0.01). Women used stronger word descriptors more frequently than men. CONCLUSION: The use of specific or more word descriptors to separate patients with AMI from those without AMI was not supported by the study data. Although patients with AMI more frequently used the sensory word tearing as well as the affective words terrifying and intolerable and less frequently used the sensory word pricking and the affective word worrying than patients without AMI, the differences do not suggest a clinical profile that can be used to differentiate these clinical entities. PMID- 7989209 TI - The role of catecholamines, age, and fitness on blood pressure reactivity to dynamic exercise in patients with essential hypertension. AB - OBJECTIVE: To determine the relationship between exercise blood pressure (BP) and catecholamine levels in hypertensive subjects and, secondarily, to evaluate the influence of age and fitness level. DESIGN: Descriptive correlational. SETTING: Midwestern, university-affiliated medical center. SUBJECTS: 27 hypertensive subjects, mean age 45 years, who were free of antihypertensive medications. OUTCOME MEASURES: BP and plasma catecholamines (norepinephrine and epinephrine). INTERVENTION: Subjects were given an incremental maximal exercise test on a cycle ergometer beginning at 25 watts with workloads increasing by 25 watts every 2 minutes until exhaustion. Plasma catecholamines were measured at rest, at 100 watts, and at maximal exercise. BP, heart rate, and oxygen consumption (VO2) were measured at rest and at the end of each workload. RESULTS: Systolic and diastolic BP were unrelated to catecholamines at rest and during exercise. When subjects were evaluated according to fitness level (VO2max), resting BP was not significantly different among groups (low fitness = VO2max < or = 25 ml/kg/min; moderate fitness = VO2max 26 to 39 ml/kg/min; high fitness = VO2max > or = 40 ml/kg/min). However, an inverse relationship was observed between fitness level and rate of rise of systolic and diastolic BP during submaximal work. Multiple regression showed that fitness predicted diastolic BP response (p = 0.02) at 100 watts. Age, however, predicted systolic BP response (p = 0.015). CONCLUSIONS: Neither the level of resting nor the magnitude of BP response to exercise in hypertensive subjects was directly related to level of plasma catecholamines. The magnitude of change in BP during exercise was modulated by age and fitness level. PMID- 7989210 TI - Cardiac surgery in the octogenarian: nursing implications. AB - OBJECTIVE: To determine morbidity and mortality rates in octogenarians undergoing cardiac surgical repairs and to compare these results with a similar group of younger patients. DESIGN: Retrospective, two-group. SETTING: Midwestern university medical center. SUBJECTS: Group I consisted of 235 male and female patients who were all less than 80 years of age. Group II consisted of 235 male and female patients who were 80 years of age or older. Both groups underwent similar cardiac surgical procedures. OUTCOME MEASURES: Development of postoperative complications, length of hospitalization, and mortality. RESULTS: When comparing octogenarians with younger patients, octogenarians developed significantly more postoperative complications with higher operative mortality. In addition, octogenarians were hospitalized significantly longer than the younger group. CONCLUSION: These findings suggest that age is a major risk factor influencing outcome after surgery. However, by incorporating nursing interventions with geriatric concepts, those postoperative complications that are common in octogenarians may be more effectively treated and possibly prevented. With sensitive and knowledge-based care, most older patients can anticipate good recovery after cardiac surgery. PMID- 7989212 TI - Mycoplasma pneumoniae meningoencephalitis complicated by diplopia. AB - We report a case of Mycoplasma pneumoniae meningoencephalitis in which the primary neurologic manifestation was diplopia. Other neurologic findings included bilateral Babinski signs, mental confusion, and bladder incontinence. The patient responded to a course of minocycline and made an uneventful recovery. We report the first known case of Mycoplasma meningoencephalitis with diplopia. PMID- 7989211 TI - Return to work, sexual activity, and other activities after acute myocardial infarction. AB - OBJECTIVES: (1) To examine the effects of exercise alone and the additional benefit of a teaching-counseling program with exercise when compared with usual medical and nursing care on the rate of return to previous activities, and (2) to describe the rates of return to former activities of daily living after an acute myocardial infarction. DESIGN: Prospective randomized clinical trial. SETTING: Seven Northwestern hospitals. SAMPLE: 258 patients, 70 years of age or younger, with the diagnosis of acute myocardial infarction, admitted to coronary care units of participating hospitals. OUTCOME MEASURES: Return to work, sexual activity, driving, previous maximum level of activity, and activities out of the home. INTERVENTION: Subjects were randomly assigned to control group A, which received usual medical and nursing care; group B1, which received usual care plus exercise; or group B2, usual care plus exercise plus teaching-counseling sessions. Home exercise programs were prescribed for patients in groups B1 and B2. Those in group B2 also participated in the outpatient teaching-counseling program that consisted of eight group sessions pertaining to risk factor reduction and psychosocial adjustment to myocardial infarction. All subjects completed Activity Summary Questionnaires, a 12-item self-report paper and pencil questionnaire about the week's activity, each week, for 12 consecutive weeks, and at week 24 after hospital discharge. RESULTS: There were no significant differences between the three groups. Previously employed patients who returned to work did so by week 24. Patients who returned to their previous maximum level of activity resumed by week 24. Most patients returned to sexual activity, driving, and activities out of the house by week 12. CONCLUSIONS: The rates of return to activities were not significantly different between the three groups. Most patients were active earlier than previously reported. Over 50% of patients returned to sexual activity, driving, and outdoor activities by 3 weeks after acute myocardial infarction. These results are useful for health care professionals who counsel patients about expectations in activity resumption. PMID- 7989213 TI - Undergoing cardiac catheterization: the effects of informational preparation and coping style on patient anxiety during the procedure. PMID- 7989214 TI - Recombination suppressors and the evolution of new species. AB - Chromosomal rearrangements are often the only apparent difference between closely related species, although it is not clear whether they are a cause or a by product of speciation. We suggest that changes in the pattern of recombination may provide a link between chromosomal rearrangements and speciation. In models of speciation by sexual selection and by reinforcement, recombination is a major barrier to the formation of new species, primarily because it opposes the establishment of linkage disequilibrium. Here we show that in both the Felsenstein (1981) and Kirkpatrick (1982) models, a recombination suppressor is able to enhance the processes leading to speciation and increase its own frequency in the population. PMID- 7989216 TI - Purging inbreeding depression and the probability of extinction: full-sib mating. AB - Inbreeding depression has been a topic of interest in recent years from a number of perspectives, particularly in the captive breeding of endangered species. Generally, the goal of captive breeding is to avoid the detrimental effects of inbreeding depression and to retain genetic variation for future adaptation. However, an important component of another suggested approach to captive breeding is to purge rapidly the population of its genetic load so that its long-term fitness is not compromised. I have examined the effectiveness of purging the genetic load by documenting both the reduction in inbreeding depression and the increase of the probability of extinction when there is continuous full-sib mating. When the genetic load is the result of lethals, the inbreeding depression is quickly purged without a high probability of extinction, except when the total genetic load is high. On the other hand, if the load is due to detrimentals of relatively small effect, the genetic load becomes fixed, the mean fitness is reduced, and the probability of extinction may be greatly increased. In other words, the success of such a programme to purge genetic load without an increase in the probability of extinction is highly dependent upon the genetic basis of inbreeding depression, information that is not readily available for most species. PMID- 7989215 TI - Evolution of dioecy: can nuclear-cytoplasmic interactions select for maleness? AB - A model of evolution of reproductive systems, when sex is determined by both nuclear and cytoplasmic genes, is presented. Such a control of sex is known to facilitate the occurrence of female individuals in hermaphroditic populations, thus leading to gynodioecy. A two-cytotypes two-nuclear loci (two alleles at each nuclear locus) model for gynodioecy has been developed previously. Such gynodioecious systems are usually considered as stable, i.e. not leading to dioecy. In order to find out if the presence of females can select for male individuals when sex determination is nuclear-cytoplasmic, we followed the evolution of alleles responsible for female sterility. These alleles can be at the preceding loci or at a third locus. We show that male individuals can be selected. Dioecy evolves in less restrictive conditions than under nuclear sex determination. The same also holds for trioecy (coexistence of females, hermaphrodites and males). Nuclear-cytoplasmic polymorphism can be maintained in these reproductive systems. PMID- 7989217 TI - Fluctuating asymmetry does not increase with moderate inbreeding in Drosophila melanogaster. AB - Fluctuating asymmetry, the unsigned difference between character values on the left and right sides of an individual, is often thought to be highly correlated with the heterozygosity of individuals or populations. A large sample of Drosophila melanogaster individuals with an inbreeding coefficient of F = 0.25 was derived from a laboratory population and compared to a sample of outbred individuals for the fluctuating asymmetry of sternopleural bristle number. Inbred flies were not more asymmetric than outbred flies. There was no evidence for heritability of fluctuating asymmetry, as measured by variance among full-sib lines. Fluctuating asymmetry may not be a reliable measure of the degree of inbreeding at the relatively low levels found in most animal populations and should be used with caution in the management of endangered species. PMID- 7989218 TI - The mariner transposable element in the Drosophilidae family. AB - The distribution of the mariner transposable element among Drosophilidae species was investigated using three different techniques, i.e. squash blots, Southern blots and PCR amplification, using two sets of primers (one corresponding to the Inverted Terminal Repeats and the other to two conserved regions of the putative transposase). Our results and those of others show that the distribution of mariner is not uniform and does not follow the phylogeny of the host species. An analysis of geographical distribution, based on endemic species, shows that mariner is mainly present in Asia and Africa. At least two hypotheses may be proposed to explain the specific and geographical distributions of this element. Firstly, they may be the results of several horizontal transmissions between Drosophila species and/or between Drosophila species and one or several donor species outside the Drosophilidae family. Secondly, these particular distributions may correspond to the evolution of the mariner element from an ancestral copy which was present in the ancestor of the Drosophilidae family. PMID- 7989219 TI - Molecular analysis of Gpdh null mutations that arose in mutation accumulation experiments in Drosophila melanogaster. AB - In order to clarify the cause of null mutations in enzyme loci, the molecular structure of six null mutations in the Gpdh locus (encoding alpha GPDH: alpha glycerol-3-phosphate dehydrogenase (NAD+), E.C. 1.1.1.8; map position at 2-17.8) that arose in mutation accumulation experiments was examined. A restriction map analysis showed that five of the mutations are insertional mutations whereas the sixth is a deletion. The Gpdh regions of these null mutations were then cloned and sequenced. The inserted DNA fragments are all internally deleted P elements measuring 1.1 kb in length. Two are a KP element and two others are a HP element. All the insertions occur in the region near the initiation signal of transcription. The deletion encompasses the seventh and eighth exons over a length of 1.1 kb. These results therefore indicate that the null mutation rate at the Gpdh locus is largely influenced by P elements. PMID- 7989220 TI - Inversion polymorphism and extra bristles in Indian natural populations of Drosophila ananassae: joint variation. AB - Five Indian natural populations of Drosophila ananassae were analysed for chromosome inversions and the presence of individuals with extra scutellar bristles in the F1 progeny of isofemale lines initiated from naturally impregnated females. Three commonly occurring inversions were found in these populations with varying frequencies as was the number of individuals with extra bristles (e.b.). Female individuals were more often found to carry extra scutellar bristles than were males. This result reveals that polygenic loci responsible for the determination of e.b. are widespread in Indian natural populations of D. ananassae. A significant positive correlation between the inversion frequency and the number of individuals with e.b. was detected in the isofemale lines of all the five populations. The 2L inversion, alpha, was found to be closely associated with individuals with the e.b. phenotype. The observed results are compared with earlier results obtained for D. melanogaster. The association of the alpha inversion with the e.b. phenotype is discussed in relation to chromosomal evolution in the melanogaster species group. PMID- 7989222 TI - Multiple genetic control of acetate-induced olfactory responses in Drosophila melanogaster larvae. AB - Behavioural responses of Drosophila melanogaster larvae were measured in response to olfactory stimulation with an homologous series of eight aliphatic n-acetates (methyl ... octyl acetate) and with cis-vaccenyl acetate. Larvae tended to be attracted to short-chain acetates (methyl ... pentyl) and repelled by longer chain acetates (hexyl, heptyl and octyl acetate). All larvae were strongly attracted to propyl acetate, irrespective of the dose studied. Larval olfactory responses generally declined with age. Two geographical strains showed specific anosmias. Katsunuma (Japan) larvae showed no response to hexyl acetate; chromosome substitution showed this behaviour to be controlled by genes on chromosome II. Tai (Ivory Coast) larvae showed no response to pentyl acetate; chromosome substitution showed that two genetic factors were primarily involved, on the X chromosome and chromosome III. The response was modulated by chromosome II. No effect of the Y chromosome was found. Two olfactory mutants were studied, olfC (X chromosome) and Indf (chromosome III); both mutants showed abnormal responses to certain acetates. The results are discussed in terms of various models of olfactory processing and the implications of these models for the number of genes involved in olfaction. PMID- 7989221 TI - Nuclear DNA introgression across a Pyrenean hybrid zone between parapatric subspecies of the grasshopper Chorthippus parallelus. AB - Two parapatric subspecies of the European grasshopper Chorthippus parallelus meet along the Pyrenees and form a hybrid zone. A nuclear DNA sequence marker (cpnl 1), involving the presence or absence of a 5 bp insertion, was found to differentiate between the two subspecies along either side of the High Pyrenees but further electrophoretic and sequence analyses revealed that considerable mixing of the subspecific genomes had occurred towards the western and eastern ends of the Pyrenees. The cline for this marker was relatively narrow in two adjoining western central high cols (Peyrelue: 9.7 km and Portalet: 13.3 km) but was significantly wider in another central high col towards the east (Quillane: 42.3 km), indicating that a different combination of forces has been operating on this locus in different regions of the Pyrenees. PMID- 7989223 TI - [Ototoxicity exemplified by aminoglycosides and cisplatin: is there a specific antidote]. PMID- 7989224 TI - [Occupational risk factors for pharyngeal cancer. Results of the Heidelberg Pharyngeal Cancer Study]. AB - We carried out a case-control study on the role of occupational factors on the risk of pharyngeal cancer. The study was performed at the Department of Otorhinolaryngology/Head and Neck Surgery of the University of Heidelberg and comprised 105 male patients with squamous cell carcinoma of the oropharynx and/or hypopharynx and 420 randomly selected control subjects who were matched for age, sex and residential area (1:4 matching design). The study showed that 34.3% of the cancer patients and 10.1% of the control subjects worked in the construction industry. As construction workers were 26.7% of the cancer patients and 7.1% of the control subjects employed, the relative risk of pharyngeal cancer in construction workers was estimated to be 2.5 (C.I. 1.1-5.5, adjusted for alcohol and tobacco consumption). After further adjustment for alcohol and tobacco consumption, an increased risk of pharyngeal cancer was found for workers exposed to cutting oils (RR = 3.7; C.I. 1.2-11.8), iron dust (RR = 2.7; C.I. 1.0-7.0) asbestos cement (RR = 2.5; C.I. 1.0-6.1), cement (RR = 2.2; C.I. 0.9-5.2) and coal/tar products (RR = 3.6; C.I. 0.8-17.3). PMID- 7989225 TI - [Auditory results after transtemporal removal of acoustic neurinoma]. AB - A retrospective study was conducted to assess results of hearing in patients who underwent resections of acoustic neuromas via the middle fossa approach. A statistical correlation of results with preoperative clinical and audiological data determined if any prognostic indicators could be associated with successful preservation of hearing. Of 93 patients included in the study, useful hearing was preserved in 54 (58%), while hearing was preserved within 10 dB of preoperative levels in 42 patients (45%). The possibility for hearing preservation appeared to be inversely related to the size of the acoustic tumor, with hearing preserved in 39 of 65 patients (60%) with tumors less than or equal to 0.5 cm. Preoperative hearing levels and electronystagmography seemed to have no prognostic value. However, auditory brain stem responses showed that a wave V latency of less than 6.8 msec was associated with an increased chance of hearing preservation. Additionally, the presence of vertigo as a pre-operative complaint appeared to be a good prognostic indicator for successful hearing preservation. PMID- 7989226 TI - [Immunoscintigraphy of carcinomas in the area of the head-neck with technetium 99m marked monoclonal antibody 174H.64. A new diagnostic procedure]. AB - Twenty-one patients with squamous cell carcinomas of the head and neck were studied by immunoscintigraphy and immunoemission, computed tomography (ECT) using monoclonal antibody 174H.64 (Biomira Edminton) labelled with 99Tcm (Schwartz Method). Immunoscintigraphic results were compared with routine clinical assessments, including CT and ultrasonography, and were controlled by histopathological examination after surgery. All primary localizations (pT1 = 3, pT2 = 3, pT3 = 7, pT4 = 5; oropharynx 7, larynx 5, hypopharynx 3, oral cavity 3, lymph nodes 3) could be visualized, while 15 out of 18 neck lesions from tumor metastases could also be visualized (pN1 = 8, pN2 = 8, pN3 = 2). In one case with micrometastases in lymph nodes that could not be demonstrated by other methods, staging was upgraded by the immunoscintigraphic results. Three other micrometastases in lymph nodes could not be visualized. Distant metastases were suspected in 5 cases, three of which were confirmed either histologically or by radiography. Two of the cases with distant metastases were detected by the immunoscintigraphy. The present results indicate that immunoscintigraphy in combination with immuno-ECT can improve preoperative staging of head and neck carcinomas, especially with regard to metastatic neck disease, tumor recurrences and some cases of distant metastases. PMID- 7989227 TI - [Pleomorphic adenoma of the parotid gland. Results of surgical treatment]. AB - Twenty years experience of lateral parotidectomy as suspical treatment for pleomorphic adenoma are reviewed. All cases were managed at the ORL Clinic of the University of Zurich. 167 patients were followed for the frequency of possible recurrent tumors. Three patients (3/123) operated primarily developed a recurrences. Recurrences appeared after an average of 10 years, ranging from 1-30 years. The follow-up time varied from 1 to 21 years (average, 8 years). 39% (13 of 33) of the patients, who were re-operated for a recurrent tumor, developed another recurrence. The second recurrence appeared after an average of 10 years, ranging from 1-22 years. A persistent partial paresis of the facial nerve was found in 1% of the patients operated primarily and in 9% of the patients operated more than once. No paralysis was seen. We now choose "en-bloc" resections of pleomorphic adenomas without intra-operative opening of the tumor capsule as the treatment of choice. This treatment was possible in 83% of all cases, using a lateral parotidectomy. If tumor extends into the medial parotid lobe, total parotidectomy is required. PMID- 7989228 TI - [The use of autologous keratinocytes in ear surgery]. AB - To date autologous keratinocyte grafts have been used successfully to treat second- or third-degree burn wounds. This method allows a thin epithelialization of surfaces to take place but has been rarely used in otologic surgery until now. This technique has two possible indications in surgery of the external ear canal and the middle ear. We have currently used this method to cover a wound bed after resection of external ear canal stenosis and to treat large mastoid cavities with chronic secretion. Various aspects of the method as well as initial results of clinical use are shown. PMID- 7989229 TI - [Acute therapy of anaphylactoid reactions. Results of an interdisciplinary consensus conference]. PMID- 7989230 TI - [Surgical treatment of chronic otitis media. I: Indications, preoperative care and surgical principles]. AB - The two classic types of chronic otitis media--chronic suppurative disease and cholesteatoma--not only differ in their clinical course and prognosis, but they also require different therapeutic strategies. Benign chronic suppurative disease with its chronic irritating otorrhea can often be managed conservatively. Surgery is recommended if improvement of hearing is the goal, but also to heal the chronic inflammatory disease. Diagnosis of a cholesteatoma, however, is a clear indication for surgical treatment; conservative and wait-and-see strategies are the exception. Even in cases of precholesteatoma, there is an increasing tendency for surgery to be performed to halt the progress of the retraction pocket. Preparations for ear surgery comprise an extensive investigation with tympanic microscopy, audio- and vestibulometry and radiography. The information given to the patient must be comprehensive, and should include details of operative strategies and the risks involved, thus allowing the surgeons to adapt their operative techniques to intraoperative findings. Several surgical techniques are recommended for the removal of cholesteatomas. There is no "best" method, however, as shown by fluctuations in the different more or less dogmatically propagated techniques performed in the last few decades. Nowadays, the operative procedure, i.e. whether open or closed technique, retroauricular or endaural approach, is individualized, which means the appropriate technique is chosen according to the requirements of a given case. Each technique has its own specific advantages (and disadvantages) and can be employed taking into account the individual factors of the chronic ear disease to be treated in order to reduce the intolerably high recurrence rates. The acoustic results of tympanoplasty, the pathophysics of which are briefly described, are also unsatisfactory. Closure of a drum perforation alone is connected with a high success rate regardless of the material used. Hearing results of ossicular chain reconstruction depend only partially on the prosthesis material in spite of the strong propagation of modern materials. Rather, mechanical factors and unresolved problems such as continuing tubal dysfunction and chronic inflammation are crucial as regards the successful restoration of normal hearing. Postoperative complications such as inner ear trauma, facial nerve injury etc. are rare; early diagnosis and treatment of complications improve the prognosis. The careful, sometimes extensive postoperative management is necessary and must continue lifelong in cases of cholesteatoma because of the high recurrence rate. PMID- 7989231 TI - A salute to careers in disease eradication. PMID- 7989232 TI - Parasitisms of dairy and beef cattle in the United States. PMID- 7989233 TI - Development of a modular curriculum for education in nutrition. PMID- 7989234 TI - What is your diagnosis? Mineralized mass in the right caudoventral quadrant, and imperceptible serosal surfaces in the middle portion of the abdomen. PMID- 7989235 TI - What is your neurologic diagnosis? Tumor of the left portion of the brain stem. PMID- 7989236 TI - ECG of the month. Arrhythmia after anesthetic induction in a castrated male quarter horse with hirsutism and chronic laminitis. PMID- 7989238 TI - Legal brief. Unfinished business. PMID- 7989237 TI - Animal behavior case of the month. Urine spraying by a cat in a multicat household. PMID- 7989239 TI - Evaluation of serum estradiol concentrations in alopecic ferrets with adrenal gland tumors. AB - Seventeen ferrets were examined because of progressive bilaterally symmetric alopecia that was nonpruritic. Dermatologic and endocrinologic testing were used to determine the cause of the alopecia. Resting cortisol, testosterone, and thyroxin concentrations and results of ACTH stimulation tests were found to be within reference range limits established for this species. High serum estradiol concentrations were found to be a reliable indicator of adrenal cortical neoplasia in these ferrets. PMID- 7989240 TI - Evaluation of mesenteric lymphangiography and thoracic duct ligation in cats with chylothorax: 19 cases (1987-1992). AB - Mesenteric lymphangiography and thoracic duct ligation were performed on 19 cats with chylothorax between 1987 to 1992. Chylothorax was diagnosed on the basis of detection of chylomicrons in the pleural effusion or determination of a cholesterol concentration:triglyceride concentration ratio of < 1 in the pleural fluid. Preoperative medical treatment consisted of thoracentesis (19 of 19 cats) and feeding a fat-restricted diet (14 of 19 cats). Positive-contrast mesenteric lymphangiography was performed before thoracic duct ligation to identify an underlying cause for the effusion. Lymphangiectasia was diagnosed by use of radiography in 17 cats, none of which had evidence of a thoracic duct rupture. Thoracic duct ligation was performed via an incision made through the left 10th intercostal space. Lymphangiography was repeated immediately after ligation of the thoracic duct to document occlusion of all branches. Follow-up monitoring was done for 12 to 47 months (median, 28 months) and consisted of physical examination, evaluation for clinical signs related to pleural effusion, and thoracic radiography. Ten of 19 (53%) cats had complete resolution of pleural effusion. Nonchylous effusion, localized in the right hemithorax, was detected in 1 cat 2 months after thoracic duct ligation, but resolved after thoracotomy, breakdown of thoracic adhesions, and expansion of the right cranial lung lobe. Chylous effusion resolved 3 to 7 days (mean, 5.4 days) after surgery in the 10 cats that survived > 12 months after surgery. Four cats died between 2 and 13 days after thoracic duct ligation, but pleural effusion had resolved in 3 of these 4 cats at the time of death.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7989241 TI - Frequency and distribution of medial and lateral patellar luxation in dogs: 124 cases (1982-1992). AB - From the medical records of 124 dogs, patellar luxations were classified as congenital or acquired, medial or lateral, and unilateral or bilateral; were graded 1 to 4; and were subdivided according to size of dog. The 4 breed-size categories were based on guidelines from American Kennel Club standards for adult height and weight. Findings from these records were compared with the results from dogs with other orthopedic problems. A majority of dogs had congenital (91; 82%), as opposed to acquired (17; 15%) patellar luxations. Distribution of dogs with patellar luxations according to breed size included 54 (98%) with medial patellar luxations (MPL) and 1 (2%) with lateral patellar luxation (LPL) in small breeds, 17 (81%) with MPL and 4 (19%) with LPL in medium breeds, 35 (83%) with MPL and 7 (17%) with LPL in large breeds; and 4 (67%) with MPL and 2 (33%) with LPL in giant breeds. Medial patellar luxation was observed in 110 dogs and 14 dogs had LPL. Cases of MPL and LPL in the same stifle or of medial and lateral patellar luxation in contralateral stifles in the same dog were not observed. Surgical correction was performed primarily in dogs with grade-3 and grade-4 patellar luxations. Medial patellar luxations and LPL were detected in all breed categories. Small-breed dogs were admitted almost exclusively with MPL. Lateral patellar luxation was found uncommonly; however, it was observed more often in larger-breed dogs. Prevalence of MPL was greater, when compared with that for LPL, in every size/breed category. PMID- 7989242 TI - Weight, water, and cation losses in horses competing in a three-day event. AB - Body weight of 48 horses competing in a 3-day event was measured the day before the event (baseline), following the dressage phase of the event (day 1), after the endurance phases of the event (day 2), and 18 to 24 hours after the endurance phases (day 3). Plasma sodium and potassium concentrations were measured the evening before, immediately after, and 10 minutes after the endurance phases. Total body water, water loss, and net exchangeable cation loss were then calculated. Body weight and total body water were significantly decreased, compared with baseline values, at all times during the event, and significant water loss was detected. The largest changes were recorded after the endurance phases of the event. Water deficits were still detected 18 to 24 hours after the endurance phases of the event. Mean plasma sodium concentration was significantly increased immediately after the endurance phases of the event, compared with concentration measured the evening before, and remained increased after the 10 minute recovery period, presumably because of dehydration. Mean plasma potassium concentration was significantly increased immediately after the endurance phases of the event, compared with concentration measured the evening before, but was not increased after the 10-minute recovery period. PMID- 7989243 TI - Disseminated peritoneal leiomyomatosis in a horse. AB - A 6-year-old female Quarter Horse became inappetent, lost weight, was febrile, and had abdominal enlargement and infrequent bouts of mild colic. Palpation per rectum detected a prominent, smooth-walled mass adjacent to the pelvic flexure of the colon. Analyses revealed the peritoneal fluid was apparently normal except for a high protein concentration. By the use of ultrasonography, the mass was observed adjacent to the body wall in many locations throughout the abdomen, appearing as an irregular, multiloculated structure composed of innumerable cysts of various sizes with interspersed, circular hyperechoic nodules. A celiotomy was performed, and the 34-kg mass was removed. On the basis of histologic examination, a diagnosis of disseminated peritoneal leiomyomatosis was made. The horse had an uncomplicated recovery and gained weight. Further problems have not been reported and the horse subsequently gave birth to a healthy foal. A complete examination of the horse 22 months after surgery did not reveal signs of redevelopment of the condition. PMID- 7989244 TI - Surgical treatment for epiglottic entrapment in horses: 51 cases (1981-1992). AB - Medical records of 51 horses with epiglottic entrapment were reviewed, and the outcome after surgical treatment was evaluated by use of results from a survey of owners and from race records. Horses with epiglottic entrapment and no additional problem (uncomplicated) of the nares, nasal passages, pharynx, or larynx (upper airway) that were treated by transoral axial division (group 1) or resection via laryngotomy (group 2), and horses with epiglottic entrapment complicated by an additional upper airway abnormality (group 3) were compared. The cost of treatment, duration of hospitalization, time to first race start after surgery, and complication rate were significantly (P < 0.05) less in horses in group 1, compared with those in horses of group 2. Owner survey indicated that a significantly greater percentage (82%) of horses in group 1 had a successful outcome after transoral axial division, compared with that (27%) of horses in group 2. Analysis of race records indicated that performance was similar between horses in groups 1 and 2, and significantly more horses with an additional upper airway lesion (group 3) failed to return to racing than did horses with uncomplicated epiglottic entrapment (groups 1 and 2). Transoral axial division of the ary-epiglottic fold is recommended as an appropriate treatment for uncomplicated epiglottic entrapment. Resection via laryngotomy should be reserved for treatment of epiglottic entrapment associated with excessively thick and scarred aryepiglottic folds and for intermittent epiglottic entrapment in horses for which surgical correction is deemed appropriate.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7989245 TI - Ultrasonographic diagnosis of pyelonephritis in a cow. AB - A 2-year-old Holstein cow was examined because of a 2-month history of anorexia, decreased milk production, and a white vaginal discharge. Results of physical, laboratory, and ultrasound examinations were consistent with pyelonephritis. Through ultrasound examination, the right kidney and ureter were identified as structurally involved. Right nephrectomy was performed. Eight months after nephrectomy, the cow was clinically normal. In this cow, ultrasonography helped to determine disease severity, to direct the course of treatment, and to improve the accuracy of diagnosis and prognosis. PMID- 7989246 TI - Streptococcus dysgalactiae polyarthritis in dairy goats. AB - Two Saanen does on the same farm developed signs of polyarthritis. Streptococcus dysgalactiae was isolated on microbial culture of samples from multiple joints of both goats. Antibiotic susceptibility testing of the S dysgalactiae revealed resistance to tetracycline, a commonly used antibiotic to treat arthritis in goats. The isolate was susceptible to penicillin. Polyarthritis was clinically diagnosed in 25 Saanen goats on this farm over a 2-year period. Streptococcus dysgalactiae has been reported as a cause of polyarthritis in calves and lambs and should be considered as a cause of polyarthritis in adult goats. Joint fluid samples for Mycoplasma, aerobic bacterial, and Chlamydia culture and serum samples for caprine arthritis-encephalitis virus serologic testing should be obtained from live goats during clinical evaluation of herd outbreaks of polyarthritis. PMID- 7989247 TI - Detection of a cell line contaminated with hog cholera virus. AB - Cell lines from the repository of the American Type Culture Collection were examined for possible contamination with bovine viral diarrhea virus. During testing, hog cholera virus (HCV) was detected in the IB-RS-2 D10 porcine kidney cell line. This variant of HCV was avirulent for pigs and seldom induced detectable concentrations of antibody against reference viruses (HCV-Ames or bovine viral diarrhea virus-NY1) in serum of inoculated pigs. Additionally, this variant of HCV did not confer protection to pigs against virulent HCV. The contaminated cell line had been distributed to > 20 laboratories in the United States. The cell line was not used in field studies and has been destroyed. PMID- 7989248 TI - Evaluation of a rapid cultural method for identification of salmonellas in naturally contaminated veterinary samples. AB - Three thousand and forty-two samples of post-mortem tissues, environmental swabs, animal feed ingredients and eggs were examined by conventional methods and by a simple rapid culture method. The rapid method gave reliable presumptive identification of salmonella contamination within 48 h of the start of culture. The rapid method also showed enhanced sensitivity for detection of salmonellas, in most types of sample, particularly those taken in poultry houses and hatcheries where high levels of competitive faecal bacteria are present. PMID- 7989249 TI - RAPD typing for distinguishing species and strains in the genus Listeria. AB - The randomly amplified polymorphic DNA (RAPD) technique was employed in the development of a typing protocol for Listeria isolates, particularly Listeria monocytogenes strains. A single strain of L. monocytogenes was used and 200 random decamer primers were screened for their discriminatory abilities by visualizing the amplification products electrophoretically. Three candidate primers displaying potentially useful banding patterns were selected and tested against 52 L. monocytogenes strains, encompassing 11 serotypes, and 12 other strains representing five other Listeria spp. Thirty-four banding profiles were obtained with one particular primer. RAPD analysis allowed differentiation between Listeria spp. and was found to further subdivide strains of the same serotype. Where only one primer was used strains from different serotypes were occasionally found to produce identical banding profiles. RAPD analysis, which in our hands proved to be reproducible, shows much promise as a molecular alternative to traditional L. monocytogenes typing protocols. PMID- 7989250 TI - Studies on the Bacillus flora of milk and milk products. AB - Bacillus licheniformis and B. cereus were the most commonly isolated species of Bacillus found in milk at all stages of processing. Bacillus licheniformis was ubiquitous in the farm environment and counts in raw milks heat-treated in the laboratory were higher during the winter months, whilst B. cereus was associated with cattle feed throughout the year, and tended to be more common in raw milks during the summer months. Although B. licheniformis was usually isolated in larger numbers than B. cereus, this pattern changed after raw and pasteurized milks and reconstituted milk powders were pre-incubated at ambient temperatures, and B. cereus came to dominate the Bacillus population, reaching levels associated with enterotoxin production. Investigation of the growth kinetics of strains of both species showed that B. cereus grew faster than B. licheniformis at ambient temperatures. It is suggested that post-pasteurization contamination, which is commonly blamed for spoilage of milk and milk products by B. cereus, is not necessarily the most important source of this organism. PMID- 7989251 TI - Protease production by Streptomyces thermovulgaris grown on rapemeal-derived media. AB - A range of actinomycete species was tested for their ability to grow on particulate and particle-free rapeseed meal-derived media. Streptomycetes grew on both types of medium and produced a number of extracellular enzymes. Highest activities of protease were produced by Streptomyces thermovulgaris and reflected the high available protein content of rapemeal. Enzyme production and growth were analysed in fermentor-grown batch cultures of S. thermovulgaris using the particle-free rapemeal broth termed medium B. Growth was biphasic and the majority of the protease was produced during the second slower phase. Analysis of the protease as azocaseinase activity revealed a high degree of thermostability in the presence of calcium such that approximately 20% of the activity remained after incubation at 70 degrees C for 24 h. Gel filtration suggested that S. thermovulgaris synthesized more than one kind of protease and this was confirmed by using specific peptide substrates and inhibitors which revealed the presence of distinct serine and metallo-type enzymes. PMID- 7989252 TI - Inter-strain relationships among wine leuconostocs and their divergence from other Leuconostoc species, as revealed by low frequency restriction fragment analysis of genomic DNA. AB - Thirty Leuconostoc oenos strains, representing 28 different isolates, were distributed into 20 genomic groups according to PFGE patterns of restriction digests. The 8 bp-specific enzymes Sfi I, Not I and Asc I cleaved the Leuc. oenos DNA in a mean of 17, 11 and four fragments respectively and Sma I produced more than 50 fragments per genome. The strain differentiating capacity of the four enzymes was similar; only two related genomic groups failed to be distinguished by Asc I or Not I. Genomic relationships between Leuc. oenos strains were quantified by numerical analysis of Not I and Sfi I banding patterns. More than half of the strains, including the starters ML34 and PSU-1, formed a major cluster. The average size of the Leuc. oenos genome was estimated as 1.86 Mb. Although similar values were obtained for the genomes of Leuc. mesenteroides, Leuc. pseudomesenteroides, Leuc. gelidum and Leuc. citreum, a significant divergence between wine and non-wine species was inferred from comparisons of genome cleavage frequencies, determined with five different enzymes. PMID- 7989253 TI - Potentially pathogenic vibrios associated with mussels from a tropical region on the Atlantic coast of Brazil. AB - Mussels (Perna perna) harvested on the coast of Ubatuba, in three different stations in the State of Sao Paulo, Brazil, were examined for Vibrio spp. over a 1 year period. The ranges of most probable number (MPN 100 g-1) were: Vibrio alginolyticus (< 3-24,000), V. parahaemolyticus (< 3-24,000), V. fluvialis (< 3 1100), V. cholerae non-O1 (< 3-23), V. furnissii (< 3-30), V. mimicus (< 3-9) and V. vulnificus (< 3-3). The highest incidence was observed for V. alginolyticus (92-100%), followed by V. parahaemolyticus (67-92%), V. fluvialis (34-67%), V. vulnificus (8-17%), V. furnissii (0-17%), V. mimicus (0-17%) and V. cholerae non O1 (0-8%). Tests for virulence factors were positive in 34.1% of the vibrios in the rabbit ileal loop and 31.7% in the Dean test. Positive results in the Kanagawa test were obtained with 0.51% of V. parahaemolyticus strains. The mean values (MPN 100 g-1) of faecal coliforms in mussels from the three regions varied from 1100 to 44,000, and seawater collected at the same stations gave average values for faecal coliforms in the range 18-3300 MPN 100 ml-1. These results highlight the potential risks of food poisoning associated with raw or undercooked seafood. PMID- 7989254 TI - Aminopeptidase N from Streptococcus salivarius subsp. thermophilus NCDO 573: purification and properties. AB - A 96 kDa aminopeptidase was purified from Streptococcus salivarius subsp. thermophilus NCDO 573. The enzyme had similar properties to aminopeptidases isolated from lactococci and lactobacilli and showed a high degree of N-terminal amino acid sequence homology to aminopeptidase N from Lactococcus lactis subsp. cremoris. It catalysed the hydrolysis of a range of aminoacyl 4-nitroanilides and 7-amido-4-methylcoumarin derivatives, dipeptides, tripeptides and oligopeptides. In common with aminopeptidases from other lactic acid bacteria, the enzyme from Strep. salivarius subsp. thermophilus showed highest activity with lysyl derivatives but was also very active with arginyl and leucyl derivatives. Relative activity with alanyl, phenylalanyl, tyrosyl, seryl and valyl derivatives was considerably lower and with glycyl, glutamyl and prolyl derivatives almost negligible. The aminopeptidase also catalysed the hydrolysis of dipeptides and tripeptides but mostly at rates much less than that with L-lysyl-4-nitroanilide and oligopeptides. The enzyme catalysed the successive hydrolysis of various amino acid residues from the N-terminus of several oligopeptides but it was unable to cleave peptide bonds on the N-terminal side of a proline residue. PMID- 7989255 TI - Analytical procedure for use of conductance measurement to estimate Escherichia coli in shellfish. AB - Assays were performed with a Malthus AT Microbiological Analyzer to define an analytical procedure to estimate Escherichia coli counts in live bivalve shellfish by conductance measurement. The growth conditions used (Malthus Coliform Broth at 44 degrees C) were selective for E. coli, and interference was noted only when Klebsiella pneumoniae were at least 100 times as numerous as E. coli. Different sample preparation procedures and seeding conditions were tested to obtain good quality conductance curves. The best results were observed when: (a) meat and shell liquor were diluted 1:3 with tryptone salt water and homogenized in a Waring blender for 1 min at 15,000 rev min-1; and (b) the inoculum was taken from the liquid phase of the homogenate 20 min after blending and mixed immediately with the culture medium. Detection parameter threshold values were adjusted (first difference 1.5 microS for the baseline and 3.5 microS for detection, second difference 0.2 microS) to improve detection time reliability. The repeatability of conductance measurements was very good (S.D. as % response mean ranged from 1.9 to 3.3) with the protocol used. PMID- 7989256 TI - Production and viability of coccoid forms of Campylobacter jejuni. AB - Studies were conducted into the formation and physiological state of coccoid cells of a strain of the human and animal pathogen Campylobacter jejuni. It was found that growth phase and the presence of chloramphenicol did not affect the rate of shape transformation from spiral to coccoid, while nutrient limitation, aeration of the medium and the presence of free-radical scavengers had profound effects. Coccoid cells were found to reduce the tetrazolium salts INT (2-(p iodophenyl)-3-(p-nitrophenyl)-5-phenyl tetrazolium chloride) and CTC (5-cyano-2,3 ditolyl tetrazolium chloride) to their respective formazans and this was linked to cellular respiration. However, respiring coccoid cells could not sustain their existence in prolonged adverse conditions, and it was concluded that they represent a degenerative stage rather than a dormant state of the organism. PMID- 7989257 TI - Bacterial whole cell protein profiles of the rRNA group II pseudomonads. AB - Studies on bacterial whole cell protein profiles showed that members of the rRNA group II pseudomonads were distinct from other non-fluorescent and fluorescent pseudomonads, including Pseudomonas aeruginosa, the type species of the genus Pseudomonas. Strains of Ps. andropogonis, Ps. caryophylli, Ps. gladioli pv. gladioli, Ps. pickettii, Ps. pseudomallei and Ps. rubrisubalbicans showed uniform and distinct protein patterns, while strains of Ps. solanacearum and Ps. cepacia displayed differences within species. Numerical analysis of their protein profiles with GelManager and Taxan programs generated dendrograms comprising 16 clusters at 89% similarity. Each cluster included strains belonging to the same species with the exception of Ps. solanacearum, which fragmented into three clusters. Pseudomonas solanacearum showed different protein patterns correlating with different biovars and the two divisions of Cook et al. (1989), as well as the results of 16S rRNA gene sequencing. The whole cell protein profiles of a total of 83 strains belonging to 14 bacterial species were numerically analysed. PMID- 7989258 TI - Resistance of bacterial strains to dry conditions: use of anhydrous silica gel in a desiccation model system. AB - The viability of 18 bacterial strains desiccated on anhydrous silica gel and stored at a temperature of 22 degrees C for at least 3 months was determined. According to their stability in the dried state, these strains could be classified into three typical groups. Group 1, containing Gram-positive strains and Salmonella serotypes, was marked by a very slow decrease of the concentration of culturable cells from day 14 on (respectively day 21 for Salmonella thompson). The rate of decrease expressed as regression coefficient (b) ranged from 0.000389 to -0.00521 log (cfp ml-1) per d. The Group 2 strains Enterobacter cloacae and Escherichia coli did not reach a comparable slow decrease in the dry material within the indicated time period. Regression coefficients were respectively -0.04406 and -0.03412 log (cfp ml-1) per d. The reciprocal values (1/b) were respectively 23 d per log (cfp ml-1) and 29 d per log (cfp ml-1), indicating the time periods in which a reduction of 1 log unit of culturable cells occurred. Group 3 strains Pseudomonas aeruginosa, Aeromonas hydrophila and Aer. sobria were marked by a significant susceptibility to cell damage caused during desiccation and reconstitution. A high initial decrease (ID) of the concentration of culturable organisms seems to be a characteristic property of these bacterial strains: culturable organisms could not be detected after storage for 1 d (Aer. hydrophila, Aer. sobria) or 7 d (Ps. aeruginosa). The wide range of resistance of the different bacterial strains tested indicated that the silica gel model system is a suitable tool for microbiological challenge tests to investigate the survival of micro-organisms exposed to desiccation and their stability in dry materials. PMID- 7989259 TI - Haemolytic and phospholipase C (PLC) activities of Rhodococcus equi. AB - Rhodococcus equi, an intracellular organism causing pneumonia and lung abscesses in foals, is generally thought to be non-haemolytic. In the present study, however, 13 of 14 representative isolates were found to be haemolytic when tested on agar media containing washed red blood cells rather than whole blood. Red cells of rabbits, dogs, horses and man were more sensitive to lysis than were those of ruminants. Two new enzymatic activities of the species were defined: a lecithinase and a phosphatidylinositol-specific phospholipase C (PI-PLC). As judged from tests for trypsin, temperature and ethanol sensitivity, the haemolytic activity was primarily dependent on PI-PLC though the participation of lecithinase seemed probable. The haemolytic activity of growing strains, but not of cell-free preparations, was partially inhibited by lecithin but enhanced by cholesterol; however, cholesterol oxidase (CO) activity, known to mediate cooperative lysis of RBC sensitized with sphingomyelin-specific phospholipases C or D of some other species, did not contribute to the direct haemolysis caused by R. equi as demonstrated here. PMID- 7989260 TI - Survival of allochthonous bacteria in still mineral water bottled in polyvinyl chloride (PVC) and glass. AB - The mortality of Escherichia coli, Enterobacter cloacae, Klebsiella pneumoniae and Pseudomonas aeruginosa, based on the culturability of these bacteria, was assessed in non-carbonated mineral water, bottled in polyvinyl chloride (PVC) containing the indigenous flora, sterile mineral water bottled in PVC, sterile mineral water in glass containers, and sterile tap water in glass containers. There was a general decrease in the culturability of these organisms in the four test waters, except that Ps. aeruginosa grew in sterile tap water. Escherichia coli and Kl. pneumoniae had the highest mortality rates under the conditions tested, while Ent. cloacae had a very low and constant mortality rate that would have resulted in the persistence of this organism in mineral water for a long period of time. After a sharp initial decrease in culturability, Ps. aeruginosa also had a very low mortality rate in mineral water bottled in PVC. PMID- 7989261 TI - The genetic analysis of bacterial spore germination. PMID- 7989262 TI - Comparison of the fluorescent redox dye 5-cyano-2,3-ditolyltetrazolium chloride with p-iodonitrotetrazolium violet to detect metabolic activity in heat-stressed Listeria monocytogenes cells. AB - The fluorogenic redox indicator 5-cyano-2,3-ditolyltetrazolium chloride (CTC) was compared with the chromogenic p-iodonitrotetrazolium violet (INT) and conventional methods to assess cellular viability. Mild heat treatment was used as well-controlled method for producing non-viable and sub-lethally injured cells. CTC gave an underestimation of the viability of Listeria monocytogenes cells when compared with classical plating methods whereas INT gave an overestimation. However, CTC proved to be a sensitive indicator of uninjured cells. The difference between the total count and the CTC count was equivalent to the injured cell population. The fluorescent formazan formed on reduction of CTC was readily detected with a charge coupled device and cells enumerated automatically using image analysis. PMID- 7989263 TI - Enhancement of beta-galactosidase productivity of Aspergillus niger NCIM-616. AB - A series of mutations was carried out with Aspergillus niger NCIM-616 as the parent strain. A mutant strain NG-4 with 28% increased beta-galactosidase productivity was produced with N-methyl-N-nitro-N-nitrosoguanidine (NTG) at 1500 micrograms ml-1 concentration and exposure time of 60 min. This mutant yielded a third generation u.v.-treated strain, UV-5 with a 117.6% increase in beta galactosidase productivity with respect to the parent strain. PMID- 7989264 TI - Characterization and identification of Vagococcus fluvialis strains isolated from domestic animals. AB - Strains of Vagococcus fluvialis, a species of Gram-positive catalase-negative cocci, related to the genera Enterococcus and Carnobacterium, were isolated from various lesions of pigs, from lesions and tonsils of cattle and cats and from tonsils of a horse. Most lesion strains were isolated in mixed culture from animals with disease conditions unrelated to coccal infection. Certain differences with the species description of Vagococcus fluvialis were found: only a proportion of the strains was motile; many strains gave positive reactions to Voges-Proskauer, alkaline phosphatase and leucine arylamidase tests or produced acid from galactose and D-tagatose. SDS-PAGE of whole-cell protein patterns, however, confirmed the phenotypic identification. Guidelines for identification of Vagococcus fluvialis are given and an emended description of the species is proposed. PMID- 7989265 TI - Heterotrophic bacterial populations in the mineral waters of thermal springs in Spain. AB - The microbiological quality and heterotrophic bacterial populations of 26 thermal mineral water springs in Spain were studied. In most of the springs the number of viable aerobes was less than 10(3) cfu ml-1 and the number of sporulated bacteria less than 10(2) cfu ml-1. No significant differences were found in the counts obtained with Plate Count Agar (PCA) and PCA diluted 1:10 and incubated at 22 degrees, 37 degrees and 45 degrees C. Total coliforms were found in 14 springs, faecal streptococci in three, spores of sulphite-reducing Clostridium and Pseudomonas aeruginosa in seven. Neither Escherichia coli nor Staphylococcus aureus were found. A total of 665 strains were isolated and 85.4% of these identified; 329 were Gram-positive and 239 were Gram-negative. The genera most prevalent present in the springs were Pseudomonas (in 92.3%), Bacillus (65.4%), Enterobacter, Micrococcus and Staphylococcus (50%), Acinetobacter (42.3%), Arthrobacter (38.4%), Clostridium (27%) and Xanthomonas (23%). Gram-negative bacteria predominated in the mesothermal springs and Gram-positive bacteria in the hyper- and hypothermal springs. The most common Gram-negative rod species isolated were Ps. fluorescens, Ps. aeruginosa, Ps. putida, Ent. agglomerans, Ent. sakazakii, Ac. calcoaceticus and Ent. amnigenus. PMID- 7989266 TI - Influence of culture conditions on growth and protective antigenicity of Clostridium chauvoei. AB - The effect of culture conditions on growth and immunogenicity of Clostridium chauvoei were examined. The pH control and partial feeding of the carbon source at high concentrations were beneficial for growth. The biomass yield was significatively improved, however the butanol concentration reached toxic levels hampering further growth. For each experimental condition the immunogenicity of cells was tested. No differences were found with cells obtained at different temperatures, but it decreased significatively with the partial supply of the carbon source and pH control. PMID- 7989267 TI - Histamine production by wine lactic acid bacteria: isolation of a histamine producing strain of Leuconostoc oenos. AB - Populations of Leuconostoc oenos were harvested from wines containing a relatively high concentration of biogenic amines. Cultivation of the biomass in synthetic media and wine showed that it consisted of histamine-producing strains. Histamine levels after culture depended on the quantity of precursor available and on the presence of yeast lees, which certainly enriched the medium in histidine. Ethanol and pH, which control bacterial growth rate and total population, were also significant factors: pH and low ethanol concentration enhanced histamine production. Strain Leuc. oenos 9204 was isolated and studied since it retained its ability to produce histamine after several transfers. In synthetic medium this strain produced large amounts of histamine especially in the poorest nutritional conditions (no glucose, no L-malic acid). These results clearly demonstrate that Leuc. oenos involved in wine-making might play a role in biogenic amine production. The vinification method might also influence the final amine concentration in wine. PMID- 7989268 TI - Biochemical properties and whole-cell protein profiles of group G streptococci isolated from dogs. AB - Whole-cell protein profiles obtained by SDS-PAGE were used in conjunction with physiological tests to differentiate strains of Streptococcus canis isolated from dogs. Fermentation of trehalose and lactose, aesculin hydrolysis together with production of beta-D-glucuronidase and alpha-D-galactosidase allowed the demonstration of nine different biotypes. However, visual analysis of the protein patterns and comparison by the coefficient of Dice showed minor differences in band patterns among strains. Only two different profiles were observed. Although a correlation between biotyping and protein profile has been found, this kind of analysis did not provide the basis for a typing method. PMID- 7989269 TI - Regulatory effects of bifidobacteria on the growth of other colonic bacteria. AB - In the human large intestine bifidobacteria are a numerically important group of micro-organisms which are considered to exert a range of biological activities related to host health. One aspect is the inhibitory effect of these bacteria on other species, possibly excluding long term colonization by invasive pathogens. It has been suggested that the mechanism of inhibition carried out by bifidobacteria is related to the fermentative production of acids such as acetate and lactate. Experiments reported in this paper attempted to address this theory. Co-culture experiments whereby Bifidobacterium infantis was incubated with Escherichia coli and Clostridium perfringens, in a variety of fermentation systems, indicated that the bifidobacterium was able to exert an inhibitory effect not necessarily related to acid production. Further studies showed that eight species of bifidobacteria could variously excrete an anti-microbial substance with a broad spectrum of activity. Species belonging to the genera Salmonella, Listeria, Campylobacter and Shigella, as well as Vibrio cholerae, were all affected. These results show that bifidobacteria are able to exert more than one mechanism of inhibition, which may be of some importance with regard to protection against gastroenteritis. PMID- 7989270 TI - Characterization of the catalase of the genus Porphyromonas isolated from cats. AB - Crude cell extracts from members of the genus Porphyromonas isolated from cats were examined in SDS-PAGE and nondenaturing PAGE. In each of the species catalase activity was detected as a single band with characteristics of typical bacterial catalases, i.e. each catalase functioned over a broad pH range (pH 5-10), was not inhibited by chloroform-ethanol, did not possess detectable peroxidase activity, and was irreversibly inhibited by 3-amino-1,2,4 triazole. The catalase enzyme of P. gingivalis VPB 3492, P. circumdentaria NCTC 12469, P. salivosa VPB 3313 and VPB 3444 was inactivated at 71, 66.5, 63.5 and 57 degrees C respectively. The molecular weights of the enzymes from P. gingivalis VPB 3492, P. circumdentaria NCTC 12469, P. salivosa NCTC 11632 and P. salivosa VPB 3444 were 200,000, 216,000, 209,000 and 200,000 Da respectively. PMID- 7989271 TI - Characterization of an antibiotic produced by Alteromonas luteoviolacea Gauthier 1982, 85 isolated from Kinko Bay, Japan. AB - An antibiotic produced by Alteromonas luteoviolacea strain 9K-V10 was recovered after cold acetone precipitation of culture supernatant fluids or lysates that had been frozen and thawed. The precipitate obtained from cell-free lysates was fractioned by DEAE ion-exchange chromatography. Further purification by gel filtration chromatography yielded a single peak of antibiotic activity that corresponded to a protein peak with a molecular mass of approximately 100 kDa. After non-denaturing polyacrylamide gel electrophoresis, antibiotic activity co migrated with a protein band. The isoelectric point of the antibiotic was estimated to be 7.7. Treatment of the concentrated active fraction with proteinase K or heating at 70 degrees C for 10 min resulted in total loss of antibiotic activity. These results show that the antibiotic produced by Alt. luteoviolacea 9K-V10 is of a proteinaceous nature. PMID- 7989272 TI - Detection of low levels of specific Salmonella species by fluorescent antibodies and flow cytometry. AB - The use of fluorescently-labelled monoclonal antibodies, with detection by multi parameter flow cytometry, was investigated for the rapid detection of salmonellas in pure cultures. Accurate detection of specific Salmonella serotypes was demonstrated down to levels of below 10(4) cells ml-1 (within 30 min) and 1 cell ml-1 (after 6 h non-selective pre-enrichment). This level of sensitivity was attained even in the presence of high levels of other bacterial species that would otherwise have interfered with the results. With combinations of different antibodies, each with a unique fluorescent label, simultaneous analysis for two species was possible. PMID- 7989273 TI - Growth of Legionella and other heterotrophic bacteria in a circulating cooling water system exposed to ultraviolet irradiation. AB - The effect of ultraviolet irradiation on the growth and occurrence of legionella and other heterotrophic bacteria in a circulating cooling water system was studied. Water of the reservoir was circulated once in 28 h through a side-stream open channel u.v. radiator consisting of two lamps. Viable counts of legionellas and heterotrophic bacteria in water immediately after the u.v. treatment were 0 12 and 0.7-1.2% of those in the reservoir, respectively. U.v. irradiation increased the concentration of easily assimilable organic carbon. In the u.v. irradiated water samples incubated in the laboratory the viable counts of heterotrophic bacteria reached the counts in reservoir water within 5 d. The increase in viable counts was mainly due to reactivation of bacterial cells damaged by u.v. light, not because of bacterial multiplication. Despite u.v. irradiation the bacterial numbers in the reservoir water, including legionellas, did not decrease during the experimental period of 33 d. The main growth of bacteria in the reservoir occurred in biofilm and sediment, which were never exposed to u.v. irradiation. PMID- 7989274 TI - Self-presentation dynamics on overt integrity tests: experimental studies of the Reid Report. AB - Three experiments examined impression-management responses to the Reid Report Integrity Attitude Inventory. Subjects encouraged to score high on the honesty test attained higher scores than a control group, but no higher than a group of job applicants. Study 2 offered money for high scores, and provided information to use concerning the first, second, or both factors of the Reid Report. Subjects in the three information conditions scored higher than those in a control condition, but again were no higher than job applicants. In a third study, subjects were asked to respond to the Reid Report and to several other measures as if they seriously wanted a job. After the test, each subject was overpaid for the participation. Reid Report scores were significantly correlated with returning versus retaining the money. These results suggest that integrity tests possess predictive validity despite some impression-management response distortion. Relations with other personality measures also are presented. PMID- 7989275 TI - Job-specific applicant pools and national norms for cognitive ability tests: implications for range restriction corrections in validation research. AB - Correcting validity coefficients for range restriction requires the applicant pool predictor standard deviation (SD). As this is frequently unknown, some researchers use national norm SDs as estimates of the applicant pool SD. To test the proposition that job-specific applicant pools are markedly more homogeneous than broad samples of applicants for many jobs, job-specific applicant pool SDs on the Wonderlic Personnel Test for 80 jobs were compared with a large multijob applicant sample. For jobs at other than the lowest level of complexity, job specific applicant pool SDs average 10% lower than the broad norm group SDs. Ninety percent of the job-specific applicant pool SDs lie within 20% of the norm group SD, suggesting that reducing a norm group SD by 20% provides a conservative estimate of the applicant pool SD for use in range restriction corrections for other than low-complexity jobs. PMID- 7989276 TI - The impact of perceived group success-failure on motivational beliefs and attitudes: a causal model. AB - Two models describing the theoretical relationship among the constructs of perceived group success-failure, individual and collective levels of job-specific efficacy and outcome expectancy, satisfaction, and organizational commitment were developed. Model 1 proposed that the causal relationship between group success failure and subsequent attitudinal variables (satisfaction and organizational commitment) is completely mediated by efficacy and outcome expectancy variables. The second model proposed a direct causal link from perceived group success failure to the attitudinal variables and omitted questionable causal paths from personal efficacy and collective outcome expectancy to the attitudinal variables. The competing models were subjected to structural equation path model analysis. The second model produced an adequate fit between theory and data. Implications for organizations are discussed. PMID- 7989277 TI - Job and life attitudes of male executives. AB - Despite executives' important positions in organizations, their attitudes have not received much research attention. To remedy this deficiency, the authors tested a hypothesized model of executive attitudes involving job satisfaction, life satisfaction, job stress, and work-family conflict. Using data from a large, representative sample of male executives (because of the small number of female executives in the study, the analyses were confined to men), the authors obtained LISREL results indicating support for the overall model and the specific relationships within the model. These results--the first to simultaneously consider job satisfaction, life satisfaction, job stress, and work-family conflict--constitute the most comprehensive evidence to date on executive attitudes. The meaning and contributions of the findings are discussed. PMID- 7989278 TI - A study of the pharmacologic treatment of medication-compliant schizophrenics who relapse. AB - BACKGROUND: Maintenance antipsychotic medications greatly diminish the risk of relapse in schizophrenic patients. A significant number, however, will relapse despite ongoing drug treatment. This is a report of a pilot study of a group of schizophrenic patients who relapsed despite having been compliant with treatment. METHOD: The authors studied 32 schizophrenic patients who had been compliant with pharmacologic treatment but who had suffered a relapse and were admitted to the hospital. Maintained on their usual pharmacologic treatment, they also received in a double-blind fashion either fluphenazine or placebo. Clinical assessments were done on Day 1 and Day 10. RESULTS: The authors found no effect of additional neuroleptic treatment on outcome. Two-thirds of the subjects showed at least moderate improvement during the study. Subjects who were experiencing greater severity of depression on admission were more likely to improve. There was no association between baseline ratings of psychosis and outcome. CONCLUSION: This study offers preliminary evidence that increasing the dose of neuroleptic does not improve outcome in schizophrenics who have relapsed while taking antipsychotic medications. Most of these patients will improve during the course of a brief hospitalization. PMID- 7989279 TI - Akathisia and pseudoakathisia: clinical observations and accelerometric recordings. AB - BACKGROUND: Akathisia is a common side effect of neuroleptic treatment that is diagnosed on the basis of clinical observations. Its definition is regarded as complex and controversial. Thus, for example, while some authorities see akathisia as strictly an abnormal subjective state, others require the inclusion of specific repetitive movements. The present study suggests that the addition of objective accelerometric recordings to standardized clinical observations may increase the validity of this diagnosis. METHOD: Sixteen chronic schizophrenic patients, treated with various neuroleptic medications, were diagnosed as suffering from akathisia. The diagnosis was based on detailed clinical observations performed according to accepted diagnostic criteria. All patients underwent repeated accelerometric recordings following the onset of akathisia. RESULTS: While most subjects suffered from lower limb akathisia, 5 patients demonstrated the involvement of other body segments. Akathisia most frequently appeared while the patients were seated. The abnormal movements were regular, nonparoxysmal, and intermittent. Most patients suffered from a tardive disorder. The accelerometric recordings demonstrated in all cases a constant and regular wave form, frequency (below 4 Hz), and amplitude. The findings were reproducible, i.e., similar patterns appeared in several recordings of the same patient during the abnormal movements. CONCLUSION: Extensive and detailed clinical evaluations reveal that akathisia is not necessarily associated with restless pacing. Rather, the syndrome may include periodic, regular, and stereotyped movements, appearing in different body segments. Accelerometric recordings seem to confirm the clinical diagnosis of akathisia, demonstrating the existence of a constant wave form, frequency, and amplitude. In addition, these techniques may distinguish between akathisia and other disorders e.g., neuroleptic-induced tremor or tardive dyskinesia. PMID- 7989280 TI - Norplant-associated major depression and panic disorder. AB - BACKGROUND: Norplant is a long-acting subdermal implant system that is widely used for contraception. The implant releases a continuous dose of levonorgestrel, a synthetic progestin. Although oral contraceptives are associated with depression and panic disorder, no cases have been reported of psychiatric disorders secondary to the use of Norplant. METHOD: Two women, aged 18 and 29 years, are described who developed major depression and panic disorder while using the Norplant system. RESULTS: These women who had no prior psychiatric history developed major depression and panic disorder 1 to 2 months after insertion of Norplant system capsules. The symptoms worsened over the course of a year. Following removal of Norplant, the symptoms of depression and anxiety resolved within 1 month. CONCLUSION: The progesterone content of oral contraceptives has been linked to major depression and panic disorder. Since Norplant is a progestin-only preparation, it is likely that some women will develop these disorders. These cases illustrate the importance of careful follow up for adolescents and adults who select Norplant for contraception. Patients should be informed about the possible occurrence of psychiatric disorders. When evaluating new onset of depression and panic disorder in adolescent and adult women, it is important to inquire about Norplant insertion. PMID- 7989281 TI - Preliminary observations of DSM-III-R axis I comorbidity in men with paraphilias and paraphilia-related disorders. AB - BACKGROUND: We describe a comorbidity study of DSM-III-R-defined Axis I diagnoses comparing male outpatient paraphiliacs to men with nonparaphilic forms of sexual impulsivity designated as paraphilia-related disorders. METHOD: Data were prospectively collected from 60 consecutively evaluated outpatient males, aged 21 53 years, seeking treatment for the principal disorders of paraphilias (N = 34) and/or paraphilia-related disorders (N = 26). Subjects completed a semistructured psychiatric Intake Questionnaire and Sexual Inventory. The lifetime prevalence of DSM-III-R Axis I diagnoses, including disorders of sexual impulsivity, was assigned by follow-up psychiatric interviews. RESULTS: Both groups of men were diagnosed with an elevated lifetime prevalence of mood disorders (76.7%), especially early-onset dysthymia (53.3%); psychoactive substance abuse (46.7%), especially alcohol abuse (40.0%); and anxiety disorders (46.7%), especially social phobia (31.6%). The predominant forms of sexual impulsivity reported by both groups were "nonparaphilic" paraphilia-related disorders: compulsive masturbation (73.3%), protracted promiscuity (70.0%), and dependence on pornography (53.3%). CONCLUSION: There were no major differences in lifetime Axis I diagnoses to differentiate men with paraphilic disorders from those with paraphilia-related disorders. Both groups were likely to acknowledge multiple paraphilias and/or multiple paraphilia-related disorders suggesting that sexual impulsivity has diverse manifestations, which can include culturally "deviant" as well as "normative" behaviors. Several hypotheses regarding the possible etiologic relationship between depressive disorders and sexual impulsivity are suggested. PMID- 7989282 TI - Noncompliance with antiparkinsonian medications in neuroleptic-treated schizophrenic patients: three cases of an unreported phenomenon. AB - BACKGROUND: Depression is commonly associated with the longitudinal course of schizophrenia. Several etiologies for this problem have been proposed but, to our knowledge, noncompliance with antiparkinsonian medications has not been considered. METHOD: Case histories of two patients who were noncompliant and one who threatened noncompliance with antiparkinsonian medications are presented. All three patients were diagnosed with schizophrenia by DSM-III-R criteria and had been clinically stable for long periods. RESULTS: All three patients became depressed when their adjunctive benztropine was stopped, and their depressions remitted when their benztropine was reinstated. CONCLUSION: Noncompliance with antiparkinsonian medications may be associated with a reversible depression in patients receiving maintenance neuroleptics for schizophrenia. Since this is a newly described phenomenon, the scope of the problem is not known; however, it may contribute to the wide prevalence of depressive symptoms in schizophrenia. Clinical measures to facilitate detection of such noncompliance are discussed. PMID- 7989283 TI - Delirium associated with the combination of a neuroleptic, an SSRI, and benztropine. AB - BACKGROUND: On the basis of recent findings, the increased use of serotonin selective reuptake inhibitors (SSRIs) in combination with antipsychotics and concomitant benztropine is likely. METHOD: Five patients who developed delirium while receiving a neuroleptic, an SSRI, and benztropine are described. RESULTS: The timing of the delirium in relation to drug administration suggests the delirium was the result of an interaction of the SSRI and benztropine. CONCLUSION: Possible mechanisms are explored. Clinicians should be aware that patients receiving this combination may be at increased risk for delirium. PMID- 7989284 TI - Sexual obsessions associated with fluoxetine. PMID- 7989285 TI - Familial presenile dementia with motor neuron disease. PMID- 7989286 TI - Clozapine-induced orthostatic hypotension treated with fludrocortisone. PMID- 7989287 TI - Successful clozapine rechallenge following prior intolerance to clozapine. PMID- 7989288 TI - Valproate pretreatment for the difficult-to-treat patient with OCD. PMID- 7989289 TI - Social phobia: outlook for the '90s. PMID- 7989290 TI - Clinical correlates of PET- and SPECT-identified defects in dementia. AB - Functional imaging studies in patients with dementia have focused primarily on the reliability of scan patterns to correctly diagnose specific diseases, particularly Alzheimer's disease. Results from these studies have important implications as disease-specific treatments become available. A complementary approach is to examine the relationships between patterns of altered brain function and specific behaviors. This tactic has potential impact on understanding normal brain organization as well as targeting symptom-specific treatments. Regional abnormalities have been identified in dementia patients that correlate with specific behavioral deficits: disturbances of language and visuospatial function, impaired verbal fluency and selective attention, and the presence of delusions and depression. These patterns are seen in patients with Alzheimer's disease as well as with dementias of other etiologies. The specificity of these patterns for disease-specific and disease-independent symptoms is unknown. PMID- 7989291 TI - The diagnosis of Alzheimer's disease: a question of image? AB - The most common cause of dementia in the developed world is Alzheimer's disease. Histopathology is required to confirm diagnosis, but most evaluations of the accuracy of clinical criteria and neuroimaging in the diagnosis of dementia of the Alzheimer type are without such confirmation. The average specificity of clinical criteria alone is about 75%. This paper discusses the contribution of simple structural (x-ray computed tomography [CT]) and functional (Tc-99m-HMPAO single photon emission computed tomography [SPECT]) imaging to the diagnosis of Alzheimer's disease in 71 histopathologically confirmed cases (47 with Alzheimer's disease, 16 with other dementias, 8 controls) and 84 living controls. Medial temporal lobe atrophy assessed by temporal lobe-oriented CT gave 94% sensitivity and 93% specificity, while parietotemporal hypoperfusion on SPECT revealed 96% sensitivity and 89% specificity. The combination of both changes yielded a sensitivity of 90% and a specificity of 97%. These investigations clearly enhance diagnostic accuracy, can be readily applied in the clinical situation, and could be used in epidemiologic studies of Alzheimer's disease. PMID- 7989292 TI - Functional imaging in dementia: an overview. AB - Functional brain imaging using both positron emission tomography and single photon emission computed tomography has been widely applied to the study of dementing diseases. This article reviews the basic approach of the clinician to the problem of dementia, which primarily entails the exclusion of treatable or reversible causes. Structural brain imaging using magnetic resonance imaging or computed tomography to search for reversible structural brain lesions is a key component of this evaluation. Functional imaging may provide clinicians with additional information helpful in establishing the cause of dementia after a reversible illness has been ruled out. Limitations in the data supporting the use of functional images still exist, however, and these images must be interpreted in the context of the overall clinical presentation. PMID- 7989293 TI - Protein-tyrosine phosphatases. PMID- 7989294 TI - Isolation of a covalent steady-state intermediate in glutamate 60 mutants of thymidylate synthase. AB - Glutamate 60 of thymidylate synthase coordinates a hydrogen bond network important in proton transfer reactions to and from the substrate dUMP. The E60A and E60L mutants of Lactobacillus casei thymidylate synthase catalyzed tritium exchange from [5-3H]dUMP for solvent protons faster than dTMP formation, indicating accumulation of a steady-state intermediate and a change in partitioning of the intermediate. A covalent complex consisting of E60A or E60L thymidylate synthase, dUMP, and the cofactor CH2H4 folate was isolated on SDS polyacrylamide gel electrophoresis and shown to be chemically and kinetically competent to form dTMP. These results provide proof of the formation of a covalent steady-state intermediate in the reaction pathway of thymidylate synthase and demonstrate that the rate-determining step in the mutants occurs during conversion of the covalent intermediate to dTMP. PMID- 7989295 TI - Identification of a major autophosphorylation site on postsynaptic density associated Ca2+/calmodulin-dependent protein kinase. AB - One of the most abundant proteins in postsynaptic densities is identical or very similar to the alpha-subunit of the Ca2+/calmodulin-dependent protein kinase II. Autophosphorylation of this protein in isolated postsynaptic densities was studied under various conditions, following inhibition of endogenous phosphatase activity with microcystin-LR. Phosphorylation accompanied by a shift in the enzyme's electrophoretic mobility was observed upon incubation with Ca2+ and calmodulin at 37 degrees C. Brief incubation with Ca2+ and calmodulin at 0 degrees C resulted in a low level of phosphorylation and no change in mobility. Following this limited Ca(2+)-dependent phosphorylation, however, a high level of phosphorylation could be achieved in the absence of Ca2+, upon incubation at 37 degrees C. Comparison of reverse-phase HPLC phosphopeptide elution profiles obtained following phosphorylation at 37 degrees C, in the presence and absence of Ca2+, as described above, showed differences, suggesting that certain distinct sites may be phosphorylated under each condition. A major phosphopeptide peak, however, with the amino acid sequence Met-Leu-Thr(P)-Ile-Asn-Pro-Ser-Lys was identified under both conditions. This sequence is identical to the predicted sequence containing Thr-253 of the Ca2+/calmodulin-dependent protein kinase II. The results suggest that phosphorylation at Thr-253 requires an initial Ca(2+) dependent phosphorylation, which may be at a different site, but does not depend on the continued presence of Ca2+ to proceed. The observed mode of regulation of autophosphorylation at Thr-253 appears to be unique to the postsynaptic density associated enzyme. PMID- 7989296 TI - Angiotensinogen-deficient mice with hypotension. AB - The renin-angiotensin system is an enzymatic cascade that produces a potent vasoconstrictor octapeptide angiotensin II, through its physiologically inactive intermediate decapeptide angiotensin I, from their precursor angiotensinogen. In the present study, we generated angiotensinogen-deficient mice by homologous recombination in mouse embryonic stem cells. These mice do not produce angiotensinogen in the liver, resulting in the complete loss of plasma immunoreactive angiotensin I. The systolic blood pressure of the homozygous mutant mice was 66.9 +/- 4.1 mm Hg, significantly lower than that of wild-type mice (100.4 +/- 4.4 mm Hg). This profound hypotension in angiotensinogen deficient mice demonstrates an indispensable role for the renin-angiotensin system in maintaining blood pressure. PMID- 7989297 TI - Identification of the SecA protein homolog in pea chloroplasts and its possible involvement in thylakoidal protein transport. AB - Recently, we identified the SecA and SecY proteins in the cyanobacterium Synechococcus PCC7942. Antibodies raised against cyanobacterial SecA specifically reacted with a 110-kDa protein of pea chloroplasts, suggesting the presence of SecA in higher plant chloroplasts. A part of the pea secA cDNA was polymerase chain reaction-amplified with degenerated oligonucleotide primers and with pea cDNA as a template. The deduced amino acid sequence shows 62% identity with cyanobacterial SecA and 52% identity with Escherichia coli SecA. Antibodies raised against the pea SecA fragment, which was expressed in E. coli cells from the obtained polymerase chain reaction-amplified cDNA, reacted with the 110-kDa chloroplast protein; the 110-kDa protein was mainly found in the stroma but partly in the thylakoid membrane. The anti-pea SecA IgG inhibited the in vitro import of the 33-kDa protein of the oxygen-evolving complex, but not of the 23 kDa protein of the oxygen-evolving complex, into thylakoids. These results suggest that SecA facilitates transport of a subset of thylakoid lumenal proteins including the 33-kDa protein into thylakoids. We propose that a bacterial-type Sec protein-dependent transport system operates for protein transport into thylakoids in higher plant chloroplasts. PMID- 7989298 TI - A conserved 5' to 3' exonuclease activity in the yeast and human nucleotide excision repair proteins RAD2 and XPG. AB - Saccharomyces cerevisiae RAD2 protein and its human homolog xeroderma pigmentosum group G (XPG) protein function in the incision step of nucleotide excision repair of DNA damaged by ultraviolet light. Both RAD2 and XPG proteins have been shown previously to possess an endonuclease activity. Using DNA substrates labeled at either the 5' end or 3' end, we now demonstrate that RAD2 protein also digests both single-stranded and double-stranded DNAs exonucleolytically with a 5' to 3' directionality. A 5' to 3' exonuclease activity is also present in the XPG protein, indicating evolutionary conservation of this activity. The possible role of RAD2 and XPG 5' to 3' exonuclease activity in nucleotide excision repair is discussed. PMID- 7989299 TI - Oligomeric structure of Escherichia coli primary replicative helicase DnaB protein. AB - The oligomeric structure of the Escherichia coli primary replicative helicase DnaB protein in relation to the functions of the enzyme and the energetics of its stability has been characterized. Sedimentation equilibrium, sedimentation velocity, and ligand binding studies show that, in solutions containing magnesium ions, the DnaB helicase exists as a stable hexamer over a wide protein concentration range (approximately 10(-7) to 10(-5) M (hexamer)). The sedimentation coefficient of the hexamer (s0(20,w) = 10.3 +/- 0.3 S) provides an apparent frictional ratio of 1.09 +/- 0.03, which suggests that the hexamer has a nonspherical shape and, when modeled as a prolate ellipsoid of revolution, has an axial ratio of a/b = 2.6 +/- 0.6. Magnesium ions play a crucial structural role in stabilizing the hexameric structure of the DnaB helicase. In the absence of Mg2+, the DnaB protein forms a trimer that, at low protein concentrations, dissociates into monomers. Analysis of the sedimentation data indicates that the dimerization of the trimers into the active DnaB hexamer is accompanied by an uptake of approximately 4 magnesium cations. The sedimentation coefficient of the DnaB monomer (s0(20,w) = 2.8 +/- 0.3 S) provides an apparent frictional ratio of 1.22 +/- 0.05, which indicates that the monomer has an elongated structure with an axial ratio of a/b = 5.2 +/- 0.8 when modeled as a prolate ellipsoid of revolution. Analysis of the ratio of the sedimentation coefficients (the sedimentation ratio) of the DnaB hexamer and monomer, which depends solely on the shape of the protomer and the mode of aggregation, strongly suggests that elongated DnaB promoters aggregate with cyclic symmetry in which the protomer protomer contacts are limited to only two neighboring subunits. PMID- 7989300 TI - Close proximity of tryptophan residues and ATP-binding site in Escherichia coli primary replicative helicase DnaB protein. Molecular topography of the enzyme. AB - The binding of fluorescent nucleotide analogs to the Escherichia coli primary replicative helicase DnaB protein causes strong quenching of protein tryptophan fluorescence. It results from the efficient fluorescence energy transfer (E) from tryptophans to analogs bound in the nucleotide-binding site, indicating that protein tryptophans are "clustered" in close proximity to the binding site. This is in contrast to the lack of detectable energy transfer to the fluorescent single-stranded DNA (ssDNA) derivative, suggesting a distant separation between two function-linked structural elements of the enzyme, the nucleotide- and ssDNA binding sites. The dependence of E upon the average number of bound nucleotides/DnaB hexamer is nonlinear, implying a larger separation between tryptophans and the bound nucleotide in the low affinity sites. Spectroscopic studies reveal that tryptophan residues are located on the surface of the DnaB helicase in a hydrophobic cleft, whereas the environment of the tyrosines is heterogeneous, with 6 out of 10 tyrosine residues located on the surface of the helicase. The efficiency of the fluorescence energy transfer from the tyrosines to tryptophans suggests that the "centers of mass" of the residues are separated, possibly reflecting the separation of the nucleotide- and ssDNA-binding sites, with tyrosines constituting part of the ssDNA-binding region. PMID- 7989301 TI - Pyruvate dehydrogenase multienzyme complex. Characterization of assembly intermediates by sedimentation velocity analysis. AB - The pyruvate dehydrogenase complex is a large, highly organized assembly of several different catalytic and regulatory component enzymes. The structural core of the complex is the E2-X subcomplex, consisting of 60 dihydrolipoamide transacetylase (E2) subunits arranged in a pentagonal dodecahedron; 6 protein X and 2 pyruvate dehydrogenase kinase molecules are tightly associated with this E2 60-mer. The native E2-X subcomplex exhibits a sedimentation coefficient of 32 S. The effects of several chaotropes (guanidinium chloride, potassium thiocyanide, and urea) on the E2-X subcomplex were assessed. Treatment of the E2-X subcomplex with 4 M guanidinium chloride caused a complete loss of enzymatic activity and the dissociation of the subcomplex into monomeric 1.5-3 S species. Removal of the chaotrope by dialysis for 18 h resulted in complete restoration of E2 enzymatic activity and reassembly of a 32 S subcomplex; this reassembled subcomplex contained less protein X than the native subcomplex. Sedimentation velocity analysis of reassembled E2-X subcomplex demonstrated the presence of an 8 S assembly intermediate; this sedimentation coefficient is characteristic of globular proteins of molecular weights similar to that expected for a trimer of E2. Shorter periods of dialysis also gave rise to the 8 S species; the amount of this intermediate decreased with increasing times of dialysis. The 8 S species associated non-cooperatively to yield additional assembly intermediates exhibiting sedimentation coefficients of 10-32 S. PMID- 7989302 TI - Identification of a cytoplasmic Ser-Thr-Leu motif that determines agonist-induced internalization of the AT1 angiotensin receptor. AB - The type 1 angiotensin II (AT1) receptor undergoes rapid endocytosis and down regulation after agonist binding. In studies on the structural determinants of agonist-induced endocytosis, serial deletions in the cytoplasmic tail of the rat AT1a receptor showed that the carboxyl-terminal 22 amino acids are not necessary for its internalization. However, internalization was markedly impaired by the removal of one additional amino acid (Leu337) and was reduced by 95% after removal of Ser335 and Thr336. Single alanine replacements of amino acids in this region showed that individual substitutions of Thr332, Ser335, Thr336, Leu337, and Ser338 caused moderate but significant impairment of the internalization rate. Replacement of both Ser335 and Thr336 with alanine residues further impaired the internalization rate, and triple alanine replacement of the Ser-Thr Leu motif reduced internalization to almost the same extent as the corresponding tail deletion mutant. The Ser-Thr-Leu motif is highly conserved in mammalian AT1 receptors but is not present in the noninternalizing type 2 angiotensin II receptor. These data demonstrate that a serine/threonine-rich region including Leu337 in the cytoplasmic tail of the AT1 receptor is a major requirement for endocytosis of the hormone-receptor complex and support the concept that similar motifs in other G protein-coupled receptors are determinants of their agonist induced internalization. PMID- 7989303 TI - ERG10 from Saccharomyces cerevisiae encodes acetoacetyl-CoA thiolase. AB - Two recessive alleles of ERG10 and three temperature-sensitive recessive alleles of HMG1 (3-hydroxy-3-methyl-glutaryl-CoA reductase isoenzyme 1) were isolated in a screen for mevalonate auxotrophs in Saccharomyces cerevisiae. The essential, single-copy ERG10 gene was cloned by complementation of the temperature-sensitive phenotype of erg10-21. The 1,194-base pair continuous open reading frame, encoding a 398-amino acid polypeptide with a calculated molecular mass of 41,681 daltons, was demonstrated to encode cytoplasmic aceto-acetyl-CoA thiolase. Acetoacetyl-CoA thiolase activity corresponded to the number of copies of ERG10 present in cell extracts, and null alleles of ERG10 produced no detectable acetoacetyl-CoA thiolase enzyme activity. The deduced amino acid sequence was 40 95% identical to acetoacetyl-CoA thiolases from other organisms. This identity included the active site cysteines located at amino acids 91 and 384 in the Erg10 protein. PMID- 7989304 TI - Strand-specific cleavage of mismatch-containing DNA by deoxyinosine 3' endonuclease from Escherichia coli. AB - A deoxyinosine-specific endonuclease, deoxyinosine 3'-endonuclease (Yao, M., Hatahet, Z., Melamede, R. J., and Kow, Y. W. (1994) J. Biol. Chem. 269, 16260 16268), from Escherichia coli was found to recognize mismatches in DNA. Using DNA duplexes containing a unique mismatch, the enzyme was found to hydrolyze the second phosphodiester bond 3' to the mismatch. The cleavage efficiency of deoxyinosine 3'-endonuclease on mismatch-containing DNA was affected by the nature of the mismatches. The cleavage activity was also affected by the sequence context surrounding the mismatches. The presence of a G/C or C/G pair immediately 3' or 5' to the mismatch substantially reduced the ability of the enzyme to nick the mismatch-containing DNA. The presence of two G/C pairs, one 5' and the other 3' to the mismatch, abolishes the ability of the enzyme to recognize the mismatch. Interestingly, deoxyinosine 3'endonuclease showed strong strand specificity on DNA containing mismatches, and only one strand of the mismatch containing DNA was nicked by the enzyme. This strand specificity of mismatch cleavage was not affected by the nature of the mismatch. Preliminary data suggest that the strand specificity is terminus dependent; the enzyme cleaves the strand with the mismatch closer to its 5' terminus. However, when DNA duplexes containing deoxyinosine were used as substrates, deoxyinosine 3'-endonuclease cleaved exclusively the strand containing deoxyinosine. Deoxyinosine 3' endonuclease also cleaved single-stranded DNA containing deoxyinosine, but not DNA containing normal deoxynucleotides or deoxynebularine, suggesting the enzyme uses different mechanisms of recognition for deoxyinosine and mismatches in DNA. PMID- 7989305 TI - Coenzyme A dependence of glycosylphosphatidylinositol biosynthesis in a mammalian cell-free system. AB - The biosynthesis of glycosylphosphatidylinositol (GPI) in mammals and yeast involves a step not observed in trypanosomes. This reaction, which is the inositol acylation of glucosamine phosphatidylinositol (GlcN-PI), occurs as the third step in the biosynthetic pathway. In this study, conditions were developed to stimulate this reaction in vitro. The synthesis of the GlcN-PI(acyl) from either UDP-[6-3H]GlcNAc or [6-3H] GlcNAc-PI by murine lymphoma cell microsomes was greatly enhanced by the addition of either CoA or palmitoyl-CoA. Stimulation of this reaction was optimal with 1 microM of either compound and required that the precursor, GlcN-PI, be synthesized in the presence of GTP, a specific effector of the formation of this glycolipid. That GlcN-PI(acyl) was generated from GlcN-PI was established by pulse-chase analysis. Because no acyl-chain specificity for acyl-CoA stimulation of GlcN-PI(acyl) synthesis was found and attempts to demonstrate direct transfer of [3H]palmitate from [3H]palmitoyl-CoA to the third intermediate in GPI biosynthesis were unsuccessful, the possibility that free CoA was the activator of this reaction was considered. CoA-stimulated GlcN-PI acylation occurred in the absence of ATP, an essential cofactor for acyl CoA synthesis, indicating that free CoA is the endogenous effector of the third step in mammalian GPI biosynthesis. This finding is consistent with this inositol acylation being catalyzed by a CoA-dependent transacylase. Mannose-containing GPI intermediates were synthesized in vitro when GDP-mannose was added in the presence of GTP and CoA. Therefore, when effectors of the initial reactions in GPI biosynthesis are included, later steps in this pathway can be studied in mammalian cell-free systems. PMID- 7989306 TI - Shared active sites of fructose-1,6-bisphosphatase. Arginine 243 mediates substrate binding and fructose 2,6-bisphosphate inhibition. AB - The active site of pig kidney fructose-1,6-bisphosphatase (EC 3.1.3.11) is shared between subunits, Arg-243 of one chain interacting with fructose-1,6-bisphosphate or fructose-2,6-bisphosphate in the active site of an adjacent chain. In this study, Arg-243 was replaced by alanine using techniques of site-specific mutagenesis and the cloned pig kidney enzyme expressed in Escherichia coli. Compared with wild-type enzyme, kinetic parameters of the altered enzyme characterizing catalytic efficiency, magnesium binding, and inhibition by AMP differed but by less than an order of magnitude; affinity for substrate fructose 1,6-bisphosphate was 10-fold poorer, and affinity for inhibitor fructose 2,6 bisphosphate was 1000-fold poorer. Molecular dynamics simulations were undertaken to determine possible alterations in active sites of the enzyme due to replacement of Arg-243 by Ala and suggested that in the mutant enzyme loss of one cationic group leads to reorganization of the active site especially involving lysine residues 269 and 274. The differences in properties of the mutant enzyme indicate the key importance of Arg-243 in the function of fructose-1,6 bisphosphatase and confirm on a functional basis the shared active site in this important metabolic enzyme. PMID- 7989307 TI - The subunit structure of elongation factor 1 from Artemia. Why two alpha-chains in this complex? AB - Elongation factor 1 (EF-1) regulates the specific interaction of aminoacyl-tRNA with the ribosome during the elongation phase of protein biosynthesis. Although individual functions of its separate chains have been well defined, to date there is hardly information about the structure and function of the whole complex. We describe here the complete subunit structure of elongation factor 1, and discuss its change during development of Artemia. Elongation factor 1 consists of a pentameric complex, composed of four different subunits alpha, beta, gamma, and delta in a molar ratio of 2:1:1:1. Although one molecule of EF-1 alpha dissociates easily from the complex EF-1 alpha 2 beta gamma delta under the influence of aminoacyl-tRNA and GTP, the second molecule of EF-1 alpha was found to remain firmly attached. Thus, in eukaryotic protein synthesis, movement of transfer RNAs to the ribosome seems under the influence of two distinct molecules of EF-1 alpha, a result possibly related to the presumed consumption of two molecules of GTP by EF-Tu during the elongation step of prokaryotic protein synthesis. PMID- 7989308 TI - Purification and analysis of a flavoprotein functional as NADH oxidase from Amphibacillus xylanus overexpressed in Escherichia coli. AB - The gene encoding the Amphibacillus xylanus flavoprotein has been cloned into pTTQ18 and overexpressed in Escherichia coli. The recombinant enzyme has been purified to homogeneity yielding 15 mg of pure enzyme/liter of cell culture. Recombinant flavoprotein is fully active and has an absorption spectrum identical to that of the enzyme purified from A. xylanus. The N-terminal sequence analysis and analytical gel filtration data confirm the structural identity of recombinant and A. xylanus enzymes. The Km value for oxygen and the Km value for NADH are 1.7 mM and 33.3 microM, respectively. In the presence of free additional FAD, however, the Km value for oxygen decrease dramatically. The NADH oxidase activity is accelerated markedly in the presence of additional FAD. The intracellular free FAD concentration of A. xylanus is calculated about 13 microM. This FAD concentration would be enough to accelerate the NADH oxidase activity of flavoprotein in cells of A. xylanus. Two-electron reduction of the enzyme FAD by the strong reductant dithionite occurs during the total uptake of 6 electrons. Such behavior usually indicates the presence of non-flavin redox centers. The high degree of homology between this enzyme and alkyl hydroperoxide reductase F52a protein and thioredoxin reductase suggests that these centers are the redox active disulfide adjacent to the FAD and another disulfide, which is able to slowly interchange with the redox-active disulfide. The presence of two disulfides has been demonstrated. PMID- 7989309 TI - Role of tumor necrosis factor receptors in the activation of nuclear factor kappa B in human histiocytic lymphoma U-937 cells. AB - Tumor necrosis factor (TNF) has been shown to mediate numerous cellular responses through its interaction with two distinct types of receptor. However, the relationship between TNF receptor and the biological response is not well understood. Modulation of the number of cell surface receptors by various agents has shown a lack of direct correlation with biological responses to the cytokine. In this report, we used several approaches to investigate the relationship between TNF receptor number and an early response in human histiocytic lymphoma U 937 cells. When we examined the activation of the nuclear transcription factor kappa B (NF-kappa B), an event mediated by TNF within 10-15 min, we discovered a correlation between TNF receptor occupancy up to a certain threshold and the extent of activation of the transcription factor. In addition, by kinetically down-regulating TNF receptor expression with phorbol esters, cycloheximide, or trypsin, we determined that receptors were necessary for transduction of the TNF signal. However, 10-25% of total receptors were sufficient for optimum induction of the NF-kappa B signal. When examined in different cell lines, the activation of an early biological response was found to be related not only to the TNF receptor number but also to the type of TNF receptor. These results, overall, suggest that although TNF receptors are essential for induction of NF-kappa B, a small percentage is sufficient to fully transduce this signal. PMID- 7989310 TI - Lysophosphatidylcholine plays an essential role in the mitogenic effect of oxidized low density lipoprotein on murine macrophages. AB - We previously demonstrated that the growth of starch-induced murine macrophages was stimulated by modified low density lipoproteins, such as oxidized low density lipoprotein (Ox-LDL) and acetylated low density lipoprotein (acetyl-LDL), and that the mitogenic effect of Ox-LDL was much greater than that of acetyl-LDL (Yui, S., Sasaki, T., Miyazaki, A., Horiuchi, S., and Yamazaki, M. (1993) Arterioscler. Thromb. 13, 331-337). The present study was undertaken to elucidate the factor(s) that are involved in this growth-stimulating effect of Ox-LDL. The growth-stimulating effect of acetyl-LDL on murine resident macrophages was negligibly weak compared with that of Ox-LDL. However, the treatment of acetyl LDL with phospholipase A2 led to an increase in lysophosphatidylcholine (lyso-PC) (75% of total phospholipids) and a concomitant increase in the mitogenic activity of acetyl-LDL. In contrast, cell-free incubation of Ox-LDL with high density lipoprotein resulted in a decrease in lyso-PC content and a concomitant loss of growth-stimulating activity. These results suggest that lyso-PC may play an essential role in the mitogenic activity of Ox-LDL. PMID- 7989311 TI - Mechanisms for synergistic activation of thyroid hormone receptor and retinoid X receptor on different response elements. AB - The thyroid hormone receptors (TR) form heterodimers with the retinoid X receptors (RXR) and activate target genes through thyroid-responsive elements (TRE). Heterodimerization elevates the DNA binding efficiency and thus can result in functional synergism between TR and RXR. Here we demonstrate that DNA sequences dictate the cooperative activation between TR and RXR despite the high affinity binding of the heterodimer to those TREs. We provide evidence that the C terminal activation domain of RXR can modulate the triiodothyronine (T3) responsiveness of TR/RXR heterodimers on reporter genes without altering the DNA binding properties of the heterodimers. The modulation function of this relatively small region is under the control of specific TRE sequences and promoter context. These data indicate that this C-terminal region of RXR is likely involved in receptor-cellular factor(s) interactions. Finally, we propose that the synergistic activation by TR and RXR is achieved through elevated DNA binding and, dependent on the DNA sequence, the interaction of RXR with other transcription factors. PMID- 7989312 TI - PA28, an activator of the 20 S proteasome, is composed of two nonidentical but homologous subunits. AB - PA28, one of a series of a positive allosteric regulators of the 20 S proteasome, stimulates the enzyme's peptidase activities in an ATP-independent manner by binding to the terminal rings of the 20 S complex. PA28 has a native molecular mass of 180,000 Da and contains at least six subunits of approximately 28,000 Da. In this study we show that PA28 prepared from bovine heart contains two different subunits separable by reverse phase high performance liquid chromatography and that these subunits occur in approximately equal abundance. The subunits display mass values of 27,290 +/- 3.7 and 28,606 +/- 2.8 Da by electrospray mass spectrometry, showing that they differ in covalent structure. Partial amino acid sequence analysis of the subunits indicates that the subunits are the products of two different but homologous genes. A pair of subunits has also been isolated from rabbit heart, and partial amino acid sequence analysis shows each to be homologous to the corresponding subunit in bovine tissues. This indicates that the genes encoding two different polypeptide components of PA28 have been conserved during evolution and suggests the possibility that the two subunits play functionally distinct roles. Isolation of complexes formed between purified PA28 and the 20 S proteasome using density gradient centrifugation reveals that both PA28 subunits bind to the proteasome, indicating that both are components of functional PA28 molecules. These results are consistent with two alternative models for the subunit structure of PA28. There may exist two different PA28 molecules that are homooligomers of the 27,290- and 28,606-Da subunits, respectively. Alternatively, PA28 oligomers may contain mixtures of the 27,290- and 28,606-Da subunits either of fixed or variable stoichiometry. PMID- 7989313 TI - A single mutation at lysine 426 of human placental S-adenosylhomocysteine hydrolase inactivates the enzyme. AB - S-Adenosylhomocysteine (AdoHcy) hydrolase catalyzes the conversion of AdoHcy to adenosine (Ado) and homocysteine (Hcy), as well as the reverse reaction, through a mechanism involving an NAD(+)-dependent oxidation of the 3'-hydroxyl group of AdoHcy (3'-oxidative activity), followed by elimination of Hcy to form 3'-keto 4',5'-didehydro-5'-deoxy-Ado. The addition of water at the 5'-position (5' hydrolytic activity) of this tightly bound intermediate, followed by an NADH dependent reduction, results in the formation of Ado. Based on a computer graphics model of the active site of this enzyme, it was hypothesized that amino acid residues at the carboxyl-terminal end of the protein reside in the active site of the enzyme and could play a role in catalyzing the 5'-hydrolytic reaction (Yeh, J. C., Borchardt, R. T., and Vedani, A. (1991) J. Comput. Aided Mol. Des. 5, 213-234). Using site-directed mutagenesis, we show here that lysine 426 is essential for the catalytic activity of the enzyme and that it appears to play a crucial role in the 5'-hydrolytic activity and/or stability of the quaternary structure of the human placental enzyme. Mutation of Lys-426 to arginine (K426R) produces a stable tetrameric enzyme that lacks overall catalytic activity and that was isolated predominantly as its NADH form containing tightly bound 3'-keto Ado, suggesting that the K426R mutant has oxidative activity, but lacks 5' hydrolytic activity, preventing it from completing the entire catalytic cycle. Mutations of Lys-426 to glutamic acid (K426E) and alanine (K426A) produce enzymes that exist primarily as monomers, do not bind NAD+ or NADH, and lack catalytic activity. The results of the Lys-426 mutations suggest that this lysine residue is crucial for the 5'-hydrolytic activity of the enzyme and/or stabilizing the quaternary structure of the enzyme. PMID- 7989314 TI - Glucose is essential for proliferation and the glycolytic enzyme induction that provokes a transition to glycolytic energy production. AB - A transition from aerobic to anaerobic metabolism occurs as mitogen-activated thymocytes undergo proliferation. Glucose utilization and lactate formation increases 18- and 38-fold, respectively, during proliferation. The absolute amount of 14CO2 production by pyruvate dehydrogenase remains constant, while 14CO2 production by the tricarboxylic acid cycle is reduced during transition from a resting to a proliferating state. Addition of 2,4-dinitrophenol, an agent uncoupling oxidative phosphorylation, and phenacinemethosulfate, an electron acceptor, provide evidence that the reduction of glucose oxidation in proliferating thymocytes is caused neither by limitation of the tricarboxylic acid cycle itself nor by an insufficient supply of ADP. Our data suggest that enhanced cytosolic regeneration of NAD+ by induction of the glycolytic enzymes during proliferation effectively competes with NADH transport and its subsequent oxidation in the mitochondria. Mitogen-stimulated rat thymocytes cultured in a conventional medium containing glucose induce their glycolytic enzymes 8-10-fold in the S phase of the cell cycle and divide within a culture period of 72 h. Replacement of glucose by glutamine, glutamine and ribose, or glutamine and uridine prevents glycolytic enzyme induction and thymocyte proliferation. The effect of glucose on glycolytic enzyme induction cannot be mimicked by 3-O methylglucose or 2-deoxyglucose. In conclusion, glucose is required for proliferation and the glycolytic enzyme induction that mediates the transition from oxidative to glycolytic energy production during the G1/S transition of rat thymocytes. PMID- 7989315 TI - Human immunodeficiency virus nucleocapsid protein accelerates strand transfer of the terminally redundant sequences involved in reverse transcription. AB - During the initial stages of human immunodeficiency virus (HIV) replication, 5' terminally redundant (R') DNA, the minus strand synthesized as the complement of the 5'-long terminal repeat (LTR) terminal redundancy, must anneal to the 3'-LTR RNA to enable template transfer. The (R')DNA sequences contain the site involved in the tat-TAR interaction and extensive secondary structures that strongly interfere with annealing. The novel annealing reaction between (R')DNA and 3'-LTR RNA follows first-order kinetics, consistent with an unusually slow unfolding of the secondary structure as the rate-limiting step followed by a more rapid nucleation step. The HIV nucleocapsid protein accelerates the annealing reaction 3000-fold under optimal conditions. This acceleration may be necessary for strand transfer to efficiently occur in vivo and may provide a target for anti-HIV chemotherapeutic agents. PMID- 7989316 TI - Characterization and activation of naturally occurring abortive complexes of UDP galactose 4-epimerase from Escherichia coli. AB - UDP-galactose 4-epimerase catalyzes the interconversion of UDP-galactose and UDP glucose. The enzyme from Escherichia coli is a dimeric protein with an overall molecular weight of 79,000 that contains NAD+ very tightly but noncovalently bound in the enzymatic active site. NAD+ is the coenzyme for epimerization and is transiently reduced to NADH in the course of catalysis. All samples of highly purified UDP-galactose 4-epimerase contain significant amounts of NADH, and that purified after overexpression in E. coli cells contains a substantial amount of NADH. To the degree that NADH replaces enzyme bound NAD+ in the coenzyme binding site, the epimerase activity is decreased. The extinction coefficient at 345 nm for NADH in its binding site is estimated to be 3.3 mM-1 cm-1. 31P NMR spectroscopic and enzymatic analyses reveal that UDP-glucose, UDP-galactose, UDP, and UMP are gradually released from the purified enzyme upon addition of UMP or P1-5'-uridine-P2-methyl diphosphate (MeUDP). It is concluded that NADH associated with the purified enzyme is a component of inactive, abortive complexes (E-NADH uridine nucleotide) that contain tightly bound uridine nucleotides in place of the epimerization intermediate UDP-4-keto-alpha-D-hexoglucopyranose. These complexes are produced in vivo in the course of bacterial growth. The enzymatic activity of purified epimerase is increased by reaction with 1,2-naphthoquinone-4 sulfonate, which oxidizes the NADH to NAD+. Compositionally defined abortive complexes (E-NADH-uridine nucleotide) containing UMP, UDP, or UDP-hexoses (Glc/Gal) have been prepared in vitro and subjected to activation by 1,2 naphthoquinone-4-sulfonate. All are activated at rates comparable to that for the purified enzyme, although those containing UMP and UDP-hexose are more readily activated than those containing UDP. The activity of the reactivated enzyme approaches that of the most highly active epimerase that has been reported from E. coli. PMID- 7989317 TI - Suspension-mediated induction of Hepa 1c1c7 Cyp1a-1 expression is dependent on the Ah receptor signal transduction pathway. AB - We have recently demonstrated that release of normal human epithelial cells from cell-substratum and/or cell-cell adhesion generates cellular signals that induce the expression of CYP1A1 in the absence of xenobiotic polycyclic aromatic hydrocarbons (Sadek, C. M., and Allen-Hoffmann, B. L. (1994) J. Biol. Chem. 169, 16067-16074). To directly test the involvement of the Ah receptor signal transduction pathway in CYP1A1 induction following suspension of epithelial cells, we analyzed wild-type Hepa 1c1c7 cells, a subclone of the Hepa-1c1 mouse hepatoma line, and two mutant Hepa 1c1c7 lines, Class I and Class II. Suspension of wild-type Hepa 1c1c7 cells for 4 h led to an induction of steady state levels of CYP1A1 mRNA, similar to that obtained following treatment of adherent cells with 10(-9) M 2,3,7,8-tetrachlorodibenzo-p-dioxin. Mutants of the Hepa 1c1c7 cells defective in different aspects of the Ah receptor signal transduction pathway exhibited negligible (Class I) or no (Class II) suspension-mediated induction of CYP1A1 mRNA. Gel mobility shift analysis of nuclear extracts from suspended or 2,3,7,8-tetrachlorodibenzo-p-dioxin-treated wild-type cells showed that both treatments produced identical shifts in the mobility of an XRE containing probe. Antibody supershift experiments confirmed that the Ah receptor was a component of the DNA-protein complex from suspended wild-type Hepa 1c1c7 cells. These data directly demonstrate that suspension of wild-type Hepa 1c1c7 cells leads to nuclear localization and activation of the Ah receptor to a DNA binding form. PMID- 7989318 TI - The immunologically reactive part of immunopurified circulating anodic antigen from Schistosoma mansoni is a threonine-linked polysaccharide consisting of --> 6)-(beta-D-GlcpA-(1 --> 3))-beta-D-GalpNAc-(1 --> repeating units. AB - The gut-associated excretory antigen CAA (circulating anodic antigen) from adult Schistosoma mansoni worms was isolated by immunoaffinity chromatography. Amino acid analysis following alkaline borohydride treatment indicated that CAA is a glycoprotein, O-glycosylated at Thr. The primary structure of the released O glycan moiety was investigated by one- and two-dimensional, homo- and heteronuclear 1H and 13C NMR spectroscopy. It was found that the major carbohydrate chains have a novel polysaccharide structure, consisting of a branched disaccharide repeating unit containing 2-acetamido-2-deoxy-beta-D- galactopyranose (beta-D-Galp-NAc) and beta-D-glucopyranuronic acid (beta-D GlcpA). [formula: see text] The major antigenic character of CAA arises from this novel polysaccharide, which was shown to be an absolutely specific diagnostic marker in schistosomiasis. The cross-reactivity of CAA with anti-CCA (circulating cathodic antigen) monoclonal antibodies is caused by the presence of a small amount of O-linked CCA-poly-Lewis x carbohydrate chains on the CAA protein chain. PMID- 7989319 TI - Potent transactivation domains of the Ah receptor and the Ah receptor nuclear translocator map to their carboxyl termini. AB - The Ah receptor (AHR) is a ligand-activated transcription factor that is structurally related to its dimerization partner, the Ah receptor nuclear translocator (ARNT), and two Drosophila proteins, SIM and PER. All four proteins contain a region of homology now referred to as a PAS homology domain. In addition, the AHR, ARNT, and SIM harbor a basic region helix-loop-helix motif in their N termini, whereas PER does not. Previous mapping studies of the AHR have demonstrated that the PAS domain contains sequences required for ligand recognition, dimerization, and interaction with the 90-kDa heat shock protein. They also have confirmed that the basic region helix-loop-helix domain plays a role in both dimerization and sequence-specific DNA binding. To identify domains involved in transactivation of target genes, we generated chimeras of AHR/ARNT deletion mutants with the DNA binding region of the yeast Gal4 protein, transiently expressed these in COS-1 cells, and monitored their capacity to activate the chloramphenicol acetyltransferase reporter gene under the control of a minimal promoter driven by enhancer elements recognized by Gal4. Extensive analysis of these fusions revealed that the AHR and ARNT harbor potent transactivation domains within their C termini. Importantly, the amino-terminal halves of both the AHR and ARNT were found to be devoid of transactivation activity. PMID- 7989320 TI - [Ca2+]i inhibition of Ca2+ release-activated Ca2+ influx underlies agonist- and thapsigargin-induced [Ca2+]i oscillations in salivary acinar cells. AB - Inhibition of sarcoplasmic/endoplasmic reticulum Ca(2+)-ATPases by thapsigargin elicits [Ca2+]i oscillations in rat salivary gland (parotid) acinar cells which are similar to those activated by agonists but are nevertheless independent of inositol 1,4,5-trisphosphate (IP3) or IP3-sensitive Ca2+ stores (Foskett, J. K., Roifman, C. M., and Wong, D. (1991) J. Biol. Chem. 266, 2778-2782). Neither bafilomycin alone or together with monensin or chloroquine inhibited thapsigargin induced [Ca2+]i oscillations, ruling out the involvement of vacuolar-type proton pumps or organellar acidity in the mechanisms underlying them. Acute inhibition of plasma membrane Ca(2+)-ATPase by 1 mM La3+ inhibited the decline of [Ca2+]i during the falling phase of the oscillation. Acute inhibition of plasma membrane Ca2+ influx by removal of extracellular Ca2+, membrane depolarization, or inorganic channel blockers immediately abolished oscillations, even when applied during the [Ca2+]i rising phase of the cycle. Ca2+ influx rate oscillated during [Ca2+]i oscillations, varying 1.5-13-fold during a cycle. Modification of the rate of Ca2+ influx, by titrating the extent of depletion of IP3-sensitive stores or manipulating extracellular [Ca2+], indicated that oscillations depended on a high rate of Ca2+ influx. In thapsigargin- or carbachol-treated cells which did not exhibit a sustained [Ca2+]i rise or [Ca2+]i oscillations, inhibition of Ca2+ influx activated plasma membrane Ca2+ permeability. Thus, agonist- and thapsigargin-induced [Ca2+]i oscillations in parotid acinar cells appear to be generated by plasma membrane-based mechanisms which involve periodic inactivation by [Ca2+]i of the Ca2+ release-activated Ca2+ influx pathway. PMID- 7989321 TI - Dual pathways for GTP-dependent regulation of chemoattractant-activated K+ conductance in murine J774 monocytes. AB - Whole-cell patch clamp recording and digital imaging microscopy were used to investigate the electrical and calcium signaling responses of murine J774 monocytes to chemoattractants and other calcium-mobilizing agonists. A latent outwardly rectifying K+ conductance, GkOR, was elicited within seconds by each of the following agonists: C5a, ATP, ADP, interleukin-8, and the adenosine analog 5' (N-ethylcarboxamido)-adenosine. In terms of its pharmacologic profile and current voltage (I-V) relation, GkOR was very similar to a P2 purinoceptor-activated K+ conductance previously described in rat mast cells and to a K+ conductance elicited in J774 cells by the GTP analog guanosine 5'-O-(3-thiotriphosphate). Agonist-induced elevation of calcium, primarily due to intracellular release, and the induction of GkOR both required a GTP-binding protein of the Gi family, as both events were blocked by pertussis toxin; intracellular dialysis with guanosine 5'-O-(2-thiodiphosphate) also prevented the induction of GkOR, further implicating mediation by a G protein. Induction of GkOR did not depend upon influx of Ca2+, as it occurred equally well when the concentration of external Ca2+ was 100 nM or 2 mM. We attempted to uncouple agonist-induced calcium release from induction of GkOR by dialyzing the cell cytoplasm with Ca(2+)-EGTA or Ca(2+) 1,2-bis-(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid (BAPTA) buffers before agonist application. When the concentration of free Ca2+ ([Ca2+]i) was set to approximately 15 nM with 1.1 or 11 mM EGTA, a "slow"Ca2+ buffer, 10 nM C5a induced a large GkOR (11 nS at 1.1 mM EGTA versus 13.4 nS at 11 mM EGTA). Surprisingly, when [Ca2+]i was buffered at 15 nM with 10 mM BAPTA, a "rapid" Ca2+ buffer, C5a elicited a much smaller although significant K+ conductance (approximately 3 nS). Systematic increase in cytosolic [Ca2+]i upon dialysis with a series of 10 mM BAPTA-Ca2+ buffers (15-2400 nM [Ca2+]i) revealed activation of a very large K+ conductance (maximum 17.4 nS), even in the presumed absence of receptor stimulation. This conductance had a similar I-V relationship to GkOR, and activation occurred within the range of [Ca2+]i observed in intact cells following stimulation with C5a or ADP (EC50 approximately 475 nM [Ca2+]i). Activation of Gk thus may proceed in part via the release of intracellular calcium from a source in close proximity to the channel or other calcium-binding regulatory protein.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 7989322 TI - Tissue distribution of ryanodine receptor isoforms and alleles determined by reverse transcription polymerase chain reaction. AB - The tissue distribution of mRNA for ryanodine receptor (ryr) isoforms in various porcine tissues has been determined using the reverse transcription-polymerase chain reaction (RT-PCR). First strand cDNA was synthesized from total tissue RNA with reverse transcriptase and random hexamer primers. PCR primers were selected to amplify an approximately 500-base pair segment from homologous regions near the 5' end of the skeletal (ryr1), cardiac (ryr2), or brain (ryr3) ryr cDNA sequences. The specific amplification of each of the ryr isoforms was confirmed by restriction enzyme mapping and DNA sequencing. A ryr1 RT-PCR product was identified in skeletal muscle and esophagus, a ryr2 RT-PCR product was identified in cardiac muscle, aorta and esophagus, and a ryr3 RT-PCR product was identified in skeletal and cardiac muscle, aorta, esophagus, adrenal gland, small intestine, and lung. All three ryr isoforms were identified throughout the brain, including the parietal, frontal, and temporal lobes of the cerebrum, thalamus/hypothalamus, cerebellum, and brain stem. The normal (Arg615) and mutant (Cys615) ryr1 alleles were expressed in the brains of normal and malignant hyperthermia susceptible pigs, respectively. These results thus demonstrate expression of two ryr isoforms in each type of striated muscle, and all ryr isoforms in a number of regions of the nervous system. The wide distribution of ryr1 in the brain provides a possible neurogenic etiology of malignant hyperthermia. PMID- 7989323 TI - Vps34p required for yeast vacuolar protein sorting is a multiple specificity kinase that exhibits both protein kinase and phosphatidylinositol-specific PI 3 kinase activities. AB - The Vps15 protein kinase and the Vps34 phosphatidylinositol 3-kinase have been shown to function as a membrane-associated complex which facilitates the delivery of proteins to the vacuole in yeast. Biochemical characterization of the autophosphorylation reaction catalyzed by Vps15p demonstrates that it is a functional serine/threonine protein kinase. In addition, we show that the Vps34 phosphatidylinositol 3-kinase undergoes an autophosphorylation event both in vivo and in vitro, indicating that it represents a novel multiple specificity kinase capable of phosphorylating both protein and lipid substrates. Vps34p is phosphorylated predominately on serine in vivo and is able to phosphorylate serine, threonine, and tyrosine residues in vitro. Mutant Vps34 proteins containing alterations in conserved amino acids in the lipid kinase domain are severely defective for both PI 3-kinase activity and autophosphorylation. Characterization of the PI 3-kinase activity of Vps34p demonstrates that it, unlike the mammalian p110 PI 3-kinase, is highly resistant to the PI 3-kinase inhibitors wortmannin and LY294002. We also find that Vps34p is a phosphatidylinositol-specific 3-kinase, as it is able to utilize phosphatidylinositol (PtdIns) but not PtdIns(4)P or PtdIns(4,5)P2 as substrates in an in vitro PI kinase reaction. The substrate specificity, wortmannin resistance, and other biochemical characteristics of its PtdIns 3-kinase activity suggest that Vps34p is quite similar to a PtdIns-specific 3-kinase activity recently characterized from mammalian cells. These data indicate the existence of a family of PI 3-kinases composed of p110-like PI 3-kinases and Vps34p-like PtdIns-specific 3-kinases. On the basis of the role for Vps34p in vacuolar protein sorting, we propose that the production of a specific phosphoinositide, PtdIns(3)P, is involved in regulating intracellular protein sorting reactions in eukaryotic cells. PMID- 7989324 TI - Role of hydrophobicity of phenylalanine beta 85 and leucine beta 88 in the acceptor pocket for valine beta 6 during hemoglobin S polymerization. AB - Characterization of the hydrophobic EF acceptor pocket involving Phe-beta 85 and Leu-beta 88 as well as the Val-beta 6 donor site is critical for understanding the polymerization of deoxy Hb S. Glu substitutions at beta 85 or beta 88 in Hb S were made and expressed in yeast in an effort to evaluate the role of hydrophobicity in the acceptor pocket during polymerization of Hb S. Both substitutions result in decreased tetramer stability, increases in oxygen affinity, and inhibition in polymerization compared with Hb S. Critical concentrations for polymerization of Hb SF beta 85E and Hb SL beta 88E were 2.4- and 7-fold higher, respectively, than that of Hb S, while the value for Hb SL beta 88E was intermediate between those previously reported for Hb SL beta 88A and Hb SL beta 88F (Adachi, K., Konitzer, P., Paulraj, C. G., and Surrey, S. (1994) J. Biol. Chem. 269, 17477-17480). Kinetics of polymerization of Glu-beta 85 and Glu-beta 88 deoxy Hb S tetramers were biphasic at lower hemoglobin concentrations like deoxy Hb SL beta 88A, suggesting formation of two types of polymers during polymerization. The time required to form half the total amount of polymer (t1/2) for deoxy Hb SF beta 85E was 10-fold shorter than that for deoxy Hb SL beta 88E. In addition, t1/2 for deoxy Hb SF beta 85E was 2.5-fold shorter, while that for Hb SL beta 88E was 4-fold longer than deoxy Hb SL beta 88A at equivalent concentrations. These results suggest that hydrophobicity of the amino acid at beta 88 appears more critical than that at beta 85 in the acceptor pocket for Val-beta 6. Furthermore, stereospecificity of the acceptor pocket in addition to hydrophobicity of beta 88 are critical for stable hydrophobic interactions with Val-beta 6 during deoxy Hb S polymerization. PMID- 7989325 TI - Acetyl phosphate and the activation of two-component response regulators. AB - Several bacterial response regulator proteins (CheY, NRI, PhoB, and OmpR) become phosphorylated in vitro when incubated with acetyl phosphate. In the presence of high levels of acetyl phosphate and Mg2+, CheY reached steady state phosphorylation in less than 30 s; NRI and PhoB reached steady state more slowly (t1/2 to steady state of 1.5 and > 15 min, respectively). A simple method was developed to measure acetyl phosphate levels in Escherichia coli grown in defined media. Levels of acetyl phosphate were elevated in cells grown in pyruvate, glucose, and glucuronic acid and were low in cells grown in fructose, glycerol, and fumarate. The effects of varying the intracellular amounts of acetyl phosphate on chemotaxis and the osmo-response were also investigated. Acetyl phosphate was not required but did influence each of these responses. These results suggest that acetyl phosphate may influence either the sensitivity or the magnitude of an adaptive response. PMID- 7989326 TI - Novel regulation of pyruvate dehydrogenase phosphatase purified from anaerobic muscle mitochondria of the adult parasitic nematode, Ascaris suum. AB - Pyruvate dehydrogenase (PDHb) phosphatase has been purified to apparent homogeneity from mitochondria of the adult parasitic nematode, Ascaris suum. The enzyme is a heterodimer of 89 and 50 kDa, as judged by SDS-polyacrylamide gel electrophoresis. It appeared to copurify with its substrate, pyruvate dehydrogenase (E1) and could be separated by chromatography on Superose 12 in the presence of 0.5 M NaCl. Phosphatase activity was absolutely dependent on Mg2+, with an apparent Km of about 4 mM. In contrast to PDHb phosphatases from other sources, the ascarid enzyme was not stimulated by Ca2+ or spermine, but it was stimulated by L-malate, the major mitochondrial substrate in A. suum. L-Malate had no effect on the dephosphorylation of isolated [32P]E1, but it decreased the apparent Km of the phosphatase for 32P-pyruvate dehydrogenase complex or [32P]E1 in the reconstituted complex about 4-6-fold, suggesting that the dihydrolipoyl transacetylase (E2) core was necessary for malate activation. The activity of the pyruvate dehydrogenase complex (PDC) in isolated A. suum muscle mitochondria was significantly greater than that reported for other mitochondria, and the majority of the PDC appeared to be in the phosphorylated inactive state. Incubation of intact phosphorylating A. suum muscle mitochondria in the absence of substrate and the presence of an uncoupler did not lead to an activation of PDC activity. In contrast, incubation in malate plus Mg2+ markedly increased PDC activity. These results contrast markedly with those reported for aerobic mitochondria and suggest that the regulation of PDC activity in these anaerobic organelles differs significantly from that of their mammalian hosts. PMID- 7989327 TI - Mechanism of p-nitrosophenol reduction catalyzed by horse liver and human pi alcohol dehydrogenase (ADH). Human pi-ADH as a quinone reductase. AB - The mechanism of reduction of p-nitrosophenol (pNSP) catalyzed by horse liver alcohol dehydrogenase (HADH) and human pi-alcohol dehydrogenase (pi-ADH) has been compared in transient and steady-state experiments. Our results indicate that pNSP reduction catalyzed by these two ADH proceeds by different mechanisms. In one mechanism, shown by Equation 1, pNSP is reduced to p-aminophenol (pAP) via two enzymatic steps (Steps 1 and 3), which are mediated by the nonenzymatic dehydration of p-N-hydroxyaminophenol (pN-OHAP) to 1,4-benzoquinoneimine (BQI) (Step 2). [formula: see text] Pathway (I) is proposed mainly for pi-ADH but can be catalyzed by HADH. However, Step 3 is catalyzed approximately 2 orders of magnitude more slowly by HADH than by pi-ADH. This conclusion is confirmed by the results, which indicate that pi-ADH very efficiently catalyzes the reduction of BQI and 1,4-benzoquinone (BQ) to the corresponding hydroquinones. The kinetic constants determined at pH 7.4 suggest that pi-ADH is a more efficient quinone reductase and nitroso reductase than it is an ethanol oxidase or acetaldehyde reductase. An alternative mechanism of pNSP reduction, shown by Equation 2, is suggested for HADH. In this mechanism, formation of the p-hydroxybenzylnitrenium ion (pNH+P) occurs at the active-site zinc ion of the enzyme (Step 2) and accelerates further nonenzymatic reduction to pAP or hydrolysis to BQ (Step 3). [formula: see text] PMID- 7989328 TI - Conformational changes of lipoxygenase (LOX) in modified environments. Contribution to the variation in specificity of soybean LOX type 1. AB - The addition of water-soluble cosolvents in the reaction medium of type 1 soybean lipoxygenase can modify the selectivity of the enzyme in the hydroperoxide synthesis reaction. This also results in changes in secondary reactions such as carbonyl compound formation. The possibility of a conformational change of the enzyme due to variations in its microenvironment was considered. Using enzyme immobilization and laser visible Raman spectroscopy, both indirect and direct observations of such a protein conformational rearrangement are described. Subtle modifications in the secondary and/or tertiary structures, for example in microenvironments of Tyr and Trp residues, in orientations of lateral side chains were evidenced, and their importance to enzyme specificity is discussed. PMID- 7989329 TI - Activity and in vitro reassembly of the coated vesicle (H+)-ATPase requires the 50-kDa subunit of the clathrin assembly complex AP-2. AB - We have previously shown that the 50-kDa subunit of the clathrin assembly complex AP-2 (AP50) stoichiometrically binds to and is immunoprecipitated with the vacuolar (H+)-ATPase (V-ATPase) from clathrin-coated vesicles (Myers, M., and Forgac, M. (1993) J. Biol. Chem. 268, 9184-9186). We now report that treatment of stripped coated vesicles with cystine results in a purified V-ATPase complex lacking the AP50 polypeptide. Removal of AP50 can be reversed upon treatment of the vesicles with dithiothreitol. Removal of AP50 reduces the ATPase activity of the purified V-ATPase by 90% relative to the enzyme containing AP50. This inhibition is not reversed upon treatment of the AP50-depleted enzyme with dithiothreitol in the absence of AP50. The reconstituted V-ATPase depleted of AP50 is devoid of ATP-dependent proton transport activity. We observe further that the peripheral V1 subunits are unable to reassemble onto the integral V0 domain in the absence of AP50. The addition of purified AP-2 containing the AP50 polypeptide restores the ability of the V1 subunits to assemble with the V0 sector to give a V-ATPase complex that is functional in ATP-dependent proton transport. These results indicate that the AP50 polypeptide is necessary for both activity and in vitro reassembly of the V-ATPase complex. PMID- 7989330 TI - Purification and characterization of the mammalian myosin light chain phosphatase holoenzyme. The differential effects of the holoenzyme and its subunits on smooth muscle. AB - We have purified to homogeneity from the myofibrillar fraction of pig bladder a mammalian heterotrimeric form of PP-1, SMPP-1M. Purified pig bladder SMPP-1M is similar in composition and substrate specificity to avian gizzard PP-1M reported by Alessi et al. (Alessi, D., Macdougall, L. K., Sola, M. M., Ikebe, M., and Cohen, P. (1992) Eur. J. Biochem. 210, 1023-1035) and consists of the catalytic subunit of PP-1 (37 kDa) and two other equimolar subunits of 130 and 20 kDa. The properties of SMPP-1M and the role of its regulatory subunits in the dephosphorylation of myosin and in the initiation of relaxation were characterized both in vitro and in smooth muscle. We show that the relaxant effect of the catalytic subunit in smooth muscle is markedly potentiated by the addition of the regulatory subunits of SMPP-1M. Our findings demonstrate that SMPP-1M is the major phosphatase dephosphorylating myosin in mammalian smooth muscle and that myosin dephosphorylation is regulated in vivo via targeting subunits that specifically alter the substrate specificity of PP-1C toward myosin. PMID- 7989331 TI - Modification of GTP-activated calcium translocation by fatty acyl-CoA esters. Evidence for a GTP-induced prefusion event. AB - A sensitive and specific GTP-activated Ca2+ translocation process induces rapid Ca2+ movements within cells and appears to reflect G protein-induced membrane fusion or junctional communication between discrete subpopulations of Ca(2+) pumping organelles (Ghosh, T. K., Mullaney, J. M., Tarazi, F. I., and Gill, D. L. (1989) Nature 340, 236-239). Since fatty acylation can modify G protein action, modification of GTP-induced Ca2+ translocation by fatty acyl-CoA was investigated to throw light on the mechanism underlying Ca2+ transfer. Using permeabilized DDT1MF-2 smooth muscle cells, 2 microM palmitoyl-CoA completely blocked Ca2+ release activated by 20 microM GTP, while having no effect on inositol 1,4,5 trisphosphate-induced Ca2+ release. The IC50 (50% inhibitory concentration) for palmitoyl-CoA was 0.5 microM. Above 3 microM, palmitoyl-CoA inhibited Ca2+ accumulation. Fatty acyl chain length was important, C-13 to C-16 fatty acyl-CoA esters all fully blocking the action of GTP; the IC50 for myristoyl-CoA was also 0.5 microM. C-18 or larger acyl groups had diminished effectiveness as did C-8 or smaller acyl groups. Acetyl-CoA had no blocking effect. In contrast, 10 microM CoA itself blocked GTP-induced Ca2+ release. CoA required a free sulfhydryl group to block, desulfo-CoA having no effect. Removal of ATP by hexokinase and glucose prevented the action of CoA but not palmitoyl-CoA. The free sulfhydryl and ATP requirements indicated CoA was being acylated by endogenous fatty-acyl-CoA synthetase to be effective. The nonhydrolyzable myristoyl-CoA analog, S-(2 oxopentadecyl)-CoA, blocked the GTP effect identically to myristoyl- and palmitoyl-CoA (IC50 = 0.5 microM); thus, fatty acyl transfer is not required, indicating that blockade is due to a direct allosteric modification of a component of the GTP-activated process by acyl-CoA esters. Palmitoyl-CoA not only inhibited but completely reversed GTP-activated Ca2+ release, resulting in the released Ca2+ being taken back up into pools. In the presence of oxalate, GTP activated Ca2+ transfer results in a substantial increase in Ca2+ accumulation; palmitoyl-CoA also completely reversed this effect resulting in rapid termination of Ca2+ uptake. This reversal provides strong evidence that GTP-activated Ca2+ translocation does not reflect a membrane fusion event. Instead, it likely represents formation of a reversible junction or pore between organelles which may be a required prefusion event. PMID- 7989332 TI - Mutations at histidine 412 alter zinc binding and eliminate transferase activity in Escherichia coli alkaline phosphatase. AB - His-412 in wild-type Escherichia coli alkaline phosphatase is a direct ligand to one of the two zinc atoms critical for the function of the enzyme. To investigate the function of this residue, site-specific mutagenesis was used to substitute His-412 with asparagine and alanine, generating mutant enzymes H412N and H412A, respectively. Both mutant enzymes show a 5-fold decrease in kcat and 30-fold increase in Km when compared to the corresponding kinetic parameters for the wild type enzyme. In contrast to the wild-type enzyme, Tris and ethanolamine inhibit both the mutant enzymes by inhibiting the hydrolysis reaction and not participating in the transferase reaction; furthermore, both mutants have lower zinc and phosphate content than the wild-type enzyme. The addition of Zn2+ to the H412N and H412A enzymes restores catalytic activity to within 2-fold of the value for the wild-type enzyme, but more importantly the presence of Zn2+ completely restores substrate affinity. The similarity in the kinetic parameters for the H412N and H412A enzymes in the absence and presence of zinc suggests that the asparagine side chain does not play a significant role in coordinating zinc. Furthermore, both the asparagine and alanine substitutions reduce the affinity of the resulting enzymes for zinc. The pH profiles for the two mutant enzymes are different than the pH profile observed for the wild-type enzyme, suggesting that the amino acid substitutions may have altered the pKa of the zinc coordinated water molecule that is critical in the second step of the mechanism. These data suggest that His-412 does not directly participate in the catalytic mechanism but is mainly involved in zinc binding, and therefore is also indirectly involved in substrate binding and product release. PMID- 7989333 TI - Mutational analysis of polymeric immunoglobulin receptor/ligand interactions. Evidence for the involvement of multiple complementarity determining region (CDR) like loops in receptor domain I. AB - The polymeric Ig receptor (pIgR) mediates the transport of IgA and IgM across a variety of mucosal epithelia. The ectodomain of this receptor consists of five immunoglobulin-like domains (I-V), the first four being structurally similar to immunoglobulin variable regions, and the fifth to Ig constant regions. This study examines the structural features of the pIgR that participate in binding of the ligand, dimeric IgA (dIgA). Recent evidence suggests that a highly conserved region of the first Ig-like domain (domain I) may be important in this process (Bakos, M.A., Kurosky, A., and Goldblum, R. M. (1991) J. Immunol. 147, 3419 3426). In support of this hypothesis, molecular modeling of domain I places this conserved region in an exposed loop analogous to the CDR1 loop of Ig, suggesting that interactions between dIgA and the pIgR may be similar to those between antibodies and their cognate antigens. To test this hypothesis directly, we performed a mutagenic analysis of all three CDR-like loops in domain I of the pIgR. We found that point mutations in multiple residues of CDR1 produced effects on IgA binding ranging from minimal (90% of control) to profound (7%). In addition, we replaced regions corresponding to the CDR2 and CDR3 loops of domain I with their counterparts from domain II (which does not bind IgA), which in both cases resulted in complete abrogation of IgA binding. Taken together, these data suggest that each of the three CDR-like loops of domain I of the rabbit pIgR participates in the binding of dimeric IgA. PMID- 7989334 TI - Inhibition of the human methylmalonyl-CoA mutase by various CoA-esters. AB - Human methylmalonyl-CoA mutase is inhibited by ethylmalonyl-CoA, cyclopropylcarbonyl-CoA carboxylate, and methylenecyclopropylacetyl-CoA, which are substrate, intermediate, and product analogs, respectively. The mode of inhibition by each analog is reversible and mixed with respect to the substrate, methylmalonyl-CoA. This implies that the inhibitors are able to bind to both free enzyme and to the enzyme-substrate complex, although with affinities that are 4.5 to 10-fold different for the two species. The Ki1 for the cyclopropylcarbonyl CoA carboxylate (0.26 +/- 0.07 mM), is 4-fold greater than the Km(app) measured for the substrate, methylmalonyl-CoA. Additionally, ethylmalonyl-CoA functions as an alternate substrate and is metabolized to methylsuccinyl-CoA. The human mutase is a homodimer that binds 1 mol of cobalamin per subunit. So, the observed mixed inhibition kinetics by substrate analogs is curious. Our finding that methylenecyclopropylacetyl-CoA, the causative agent of Jamaican "vomiting sickness," inhibits methylmalonyl-CoA mutase, while interesting, is probably not physiologically important because of the relatively high inhibition constants (Ki1 = 0.47 +/- 0.12 mM and Ki2 = 2 +/- 0.34 mM) observed with this compound. PMID- 7989335 TI - The vertebrate peptide antibiotics dermaseptins have overlapping structural features but target specific microorganisms. AB - The physiological significance of the occurrence of sequence similar antimicrobial peptides in frog skin, as the bombinins in Bombina, the magainins in Xenopus, and the dermaseptins in Phyllomedusa, is a major unanswered question. Dermaseptins s1, s2, s3, s4, and s5, a family of cationic (lysine-rich), amphipathic antifungal peptides of 28-34 residues were thus synthesized, purified to homogeneity, and evaluated for their growth-inhibition activity in vitro against various pathogenic microorganisms. Although all five of these peptides shared a similar spectrum of lytic activity against the filamentous fungi that are responsible for opportunistic lethal infections that follow the immunodeficiency syndrome or the use of immunosuppressive agents, they exhibited marked differences in their potencies to arrest the growth of Gram-positive and Gram-negative pathogenic bacteria and yeasts. Likewise, whereas dermaseptins s1 and s5 were devoid of hemolytic activity, dermaseptin s4 caused lysis of erythrocytes at micromolar concentrations. The dermaseptins exhibited dramatic synergy of action upon combination, resulting in some cases in a 100-fold increase in antibiotic activity of the mixture over the activity of the peptides separately. Shortening the peptide chain of dermaseptin s3 to dermaseptin s3-(1 16)-NH2 did not affect the antimicrobial potency of the peptide. Further reduction of the chain length yielded peptide derivatives gradually showing reduced activity. Surprisingly, however, analogs of dermaseptin s3 as shorter as 10-12 residues in length remained fully active against Enterococcus faecalis, Cryptococcus neoformans, and against Aeromonas caviae, the causal agent of red leg disease in amphibians. Overall, these results suggest that, despite 40% sequence similarities, the dermaseptins have distinct spectra of anti-microbial activity and may act in concert to circumvent host invasion by providing frogs with a better shielding against a broad array of microorganisms. They also demonstrate the potential usefulness of short analogs of these peptides as potential candidates for biorational design of germicides. PMID- 7989336 TI - Specificity of the high affinity interaction of protein kinase C with a physiological substrate, myristoylated alanine-rich protein kinase C substrate. AB - Although myristoylated alanine-rich C kinase substrate (MARCKS), has been employed as an indicator for the activation of protein kinase C (PKC) in intact cells, little is known about its specificity for PKC family members. To address this question, we partially purified human MARCKS from baculovirus-infected cells and compared the kinetic parameters for phosphorylation by PKC isozymes, conventional PKC alpha (cPKC alpha), novel PKC delta (nPKC delta), nPKC epsilon, and atypical PKC zeta (apKC zeta), all of which are distributed in a wide variety of cells. cPKC alpha, nPKC delta, and nPKC epsilon efficiently phosphorylated intact MARCKS protein in vitro. The affinity of MARCKS for cPKC alpha, nPKC delta, and nPKC epsilon was extremely high and decreased in the order alpha > delta > epsilon with Km values of 10.7, 20.7, and 29.8 nM, respectively. The rate of phosphorylation also decreased in the same order. In contrast, a PKC zeta did not phosphorylate MARCKS efficiently, and we were unable to estimate the kinetic parameters. These results suggest that cPKC alpha, nPKC delta, and nPKC epsilon but not a PKC zeta are enzymes that phosphorylate MARCKS in response to PKC activators in intact cells. The structural requirements of MARCKS for efficient phosphorylation by these PKC members were then examined using a peptide that surrounds the phosphorylation site of MARCKS (peptide MARCKS). Interestingly, intact MARCKS showed a 90-150 times lower rate of phosphorylation by PKCs compared with peptide MARCKS, whereas the former showed a 40-180 times higher affinity for these PKC members. This implies that intact MARCKS protein retains a very high affinity for PKC with the sacrifice of its phospho-accepting activity. The structural requirements of PKC were then examined using a calpain-cleaved active fragment of nPKC delta. MARCKS was phosphorylated by the active catalytic fragment as efficiently as by intact nPKC delta, indicating that the kinase domain is sufficient for the high affinity interaction with intact MARCKS. However, gel overlay assay revealed that both intact nPKC delta and its regulatory domain bind to MARCKS, suggesting that both the kinase and regulatory domains of nPKC delta are involved in the high affinity interaction with intact MARCKS protein. PMID- 7989337 TI - Cloning and functional expression of a urea transporter from human bone marrow cells. AB - A rapid passive urea transport has been previously described in the mammalian renal inner medullary collecting duct epithelial cells and in mammalian erythrocytes. Recently, a vasopressin-regulated urea transporter (UT2) has been cloned from a rabbit kidney medullary cDNA library (You, G., Smith, C. P., Kanai, Y., Lee, W. S., Stelzner, M., and Hediger, M. A. (1993) Nature 365, 844-847). We now report the cloning and characterization of a complementary DNA (HUT11) encoding an urea transporter isolated from a human bone marrow library. It encodes a 43,000-Da polypeptide of 391 amino acids that exhibited 63% sequence identity with the rabbit urea transporter and a similar membrane topology. HUT11 carries 2 putative glycosylation sites and 10 cysteines, of which only 7 are conserved at an equivalent position in UT2. HUT11 transcripts have been identified in human erythroid and renal tissues. Expression studies in Xenopus oocytes demonstrated that HUT11 mediates a facilitated urea transport that was inhibited, as described in mammalian erythrocytes, by very low concentrations of phloretin, p-chloromercuribenzene sulfonate, and urea analogues. No unidirectional movements of charged molecules, glycerol, or water were associated with HUT11 expression in oocytes. These findings suggest that HUT11 is most likely responsible for the facilitated urea transport in human red blood cells. PMID- 7989338 TI - Translational control mediates the developmental regulation of the Trypanosoma brucei Nrk protein kinase. AB - The expression and function of eukaryotic protein kinases is highly regulated, primarily through transcriptional and post-translational processes. In this report we demonstrate an unusual mechanism for controlling protein kinase function, translational control. The Trypanosoma brucei Nrk loci encode predicted protein kinases. Here we show that Nrk has protein serine-threonine kinase activity and examine the expression and activity of Nrk during parasite development. While Nrk transcripts were previously found to be constitutively expressed throughout the life cycle, we now find that expression of Nrk protein is highly stage-regulated. Immunoblot analysis revealed that Nrk expression dramatically increased as the parasites differentiated from proliferative slender bloodforms to the non-proliferative stumpy bloodforms. Procyclic form organisms expressed moderate levels of Nrk. Analysis of Nrk activity demonstrated that it too was highest in stumpy bloodforms. Metabolic labeling and pulse-chase analysis demonstrated that Nrk accumulation was highest in stumpy bloodforms and indicated that Nrk abundance is primarily controlled at the level of biosynthesis rather than turnover. All Nrk mRNA was contained in the poly(A)+ fraction, and the 5' ends of the transcript were the same in each developmental stage. Thus, Nrk is under translational control. The strict developmental regulation of the Nrk enzymes within the trypanosome life cycle suggests that the Nrk protein kinase may play a role in parasite differentiation. PMID- 7989339 TI - Studies on the kinetic mechanism of pig kidney D-amino acid oxidase by site directed mutagenesis of tyrosine 224 and tyrosine 228. AB - Expression conditions in Escherichia coli of wild-type, Y224F, and Y228F mutants of pig kidney D-amino acid oxidase (DAAO) have been changed to yield more enzyme. The mutated proteins show spectral properties similar to those of the wild-type enzyme, in all oxidation-reduction states. All enzymes were studied by steady state and rapid reaction methods. Turnover numbers determined for Y224F DAAO with different substrates were similar to those of wild-type protein, while the Y228F DAAO always showed lower turnover numbers and higher Km values for the D-amino acid. Analyses of reduction traces at 450 and 550 nm of stopped-flow experiments with wild-type DAAO showed the presence of a new phase, the conversion between two different charge-transfer complexes of the reduced enzyme and imino acid product. The substitution of Tyr-228 totally abolished the formation of the long wavelength bands while Y224F DAAO showed long wavelength absorbance only for the first intermediate. Reoxidation of the reduced flavin results from reaction of oxygen with the first charge-transfer complex. The rate of reduction with D alanine as substrate was 1225,45 and 10 s-1 for wild-type, Y224F, and Y228F DAAOs, respectively. Comparison of the properties of these two mutant enzyme forms with those of the wild-type DAAO indicate that both tyrosine residues have their main function in the reductive half-reaction of the enzyme. PMID- 7989340 TI - Guanine nucleotide exchange regulates membrane translocation of Rac/Rho GTP binding proteins. AB - GTP-binding proteins of the Rho family are maintained as cytosolic complexes with RhoGDI in resting cells, but are released and translocate to the membrane during the course of cell activation. Membrane association of Rac/Rho/CDC42 was specifically induced by GTP analogs and required a heat- and trypsin-labile membrane component. Translocation was associated with the release of Rho family proteins from RhoGDI, but such release did not occur in the absence of membranes, nor was release in the absence of guanosine 5'-O-(thiotriphosphate) (GTP gamma S) sufficient for membrane association. Membrane binding was correlated with exchange of GTP gamma S for GDP on Rac, and only GTP gamma S-bound Rac became membrane localized. We propose that translocation of Rac and other members of the Rho family is controlled by membrane-associated guanine nucleotide exchange factors, providing a mechanism to regulate the release and activation of individual members of the Rho family during cell stimulation. PMID- 7989341 TI - Attenuation of ceramide-induced apoptosis by diglyceride in human myeloid leukemia cells. AB - Prior studies demonstrated that increased intracellular availability of ceramide induces apoptotic DNA degradation and cell death in the human leukemia cell lines HL-60 and U937 (Jarvis, W. D., Kolesnick, R. N., Fornari, F. A., Traylor, R. S., Gewirtz, D. A., and Grant, S. (1994) Proc. Natl. Acad. Sci. U. S. A. 91, 73-77). The present findings show that diglyceride opposes ceramide-related apoptosis in HL-60 and U937 cells. Acute (6-12-h) exposure to sphingomyelinase (100 milliunits/ml) or synthetic ceramide (10 microM) promoted apoptotic degradation of genomic DNA as indicated by (a) the appearance of both approximately 50 kilobase pair (kbp) DNA fragments and approximately 0.2-1.2-kbp DNA fragment ladders on agarose gels, (b) formation and release of small double-stranded DNA fragments, and (c) loss of integrity of bulk DNA. DNA damage was associated with reduced clonogenicity and expression of apoptotic morphology. In contrast, exposure to phospholipase C (0.001-100 milliunits/ml) or synthetic diglyceride (10 microM) failed to promote apoptosis and abolished the lethal actions of ceramide as defined by each of the indices outlined above. Ceramide-related apoptosis was also reduced by acute (6-h) exposure to tumor promoters such as phorbol dibutyrate and mezerein and the non-tumor-promoting agent bryostatin 1; conversely, chronic (24-h) pretreatment with these agents failed to modify ceramide-mediated cytotoxicity, but abolished the protective actions of diglyceride. These findings demonstrate that diglyceride and pharmacological protein kinase C activators reduce or abolish ceramide-mediated apoptosis in human leukemia cells and support the concept of a cytoprotective function for protein kinase C in the regulation of leukemic cell survival. In addition, the capacity of diglyceride to prevent very early genomic lesions (e.g. generation of 50-kbp DNA fragments) suggests that acute activation of protein kinase C arrests apoptosis at an initial stage. PMID- 7989342 TI - Regulation of cytosolic phospholipase A2 phosphorylation and eicosanoid production by colony-stimulating factor 1. AB - A colony-stimulating factor 1 (CSF-1)-dependent murine macrophage cell line (BAC1.2F5) and peritoneal macrophages were used to investigate the relationship between growth factor-dependent phosphorylation/activation of the 85-kDa cytosolic phospholipase A2 (cPLA2) and arachidonic acid metabolism. The addition of CSF-1 to quiescent BAC1.2F5 cells was followed by the rapid phosphorylation, electrophoretic gel retardation, and stable increase in the specific activity of cPLA2 that correlated with the activation of ERK kinases. cPLA2 phosphorylation depended on the presence of growth factor and persisted throughout the cell cycle. CSF-1 inhibited prostaglandin E2 production and did not enhance arachidonic acid release or increase the levels of lysophosphatidylcholine or glycerophosphocholine. Treatment of BAC1.2F5 cells with the calcium ionophore A23187 plus CSF-1 did not stimulate eicosanoid release. Instead, CSF-1 enhanced the rate of exogenous arachidonic acid incorporation into phosphatidylcholine and its subsequent transfer to phosphatidylethanolamine suggesting that higher rates of arachidonic acid acylation may contribute to the suppression of prostaglandin production. In peritoneal macrophages, ERK kinase activity was stimulated and cPLA2 was phosphorylated and activated in response to CSF-1. However, CSF-1 did not trigger eicosanoid release but did augment arachidonic acid mobilization and prostaglandin E2 production elicited by zymosan and A23187. Thus, cPLA2 phosphorylation/activation and calcium mobilization are not the only determinants for eicosanoid release, and additional components in differentiated tissue macrophages are also required. PMID- 7989343 TI - Topology of the product binding site in RNA polymerase revealed by transcript slippage at the phage lambda PL promoter. AB - In the presence of transcription substrates ATP, CTP, and UTP, a stable ternary complex containing tetranucleotide AUCA is formed on the phage lambda PL promoter (starting sequence C-3A-2C-1A+1U+2C+3A+4G+5). We show that in the absence of GTP or at undersaturating GTP concentrations the AUCA transcript synthesized at the +1 to +4 segment slips back by 3 nucleotides and is stabilized in the ternary complex in such a way that only its 2 3'-proximal bases remain paired to the 1/+1 positions of the template DNA. The slipped transcript can be extended in a template-directed manner into longer chains that can be cleaved by the GreA or GreB proteins at the +1/+2 junction. The slipped stabilized tetranucleotide delineates the "tight product binding site" of RNA polymerase responsible for stable holding of the transcript in the ternary transcription complex. The results suggest that the tight product binding site encompasses the locality within the complex where the nascent transcript detaches from the template strand of DNA. PMID- 7989344 TI - Evidence for the in vitro and in vivo interaction of Ras with protein kinase C zeta. AB - The zeta isoform of protein kinase C (zeta PKC) has been shown to be involved in the maturation of Xenopus oocytes and mitogenic signaling in fibroblasts. zeta PKC also regulates the important transcription factor nuclear factor kappa B, most probably by phosphorylation of the inhibitory molecule I kappa B. The mechanisms that control zeta PKC activity are still poorly characterized. This kinase is not activated by diacylglycerol but is potently stimulated in vitro by the products of phosphatidylinositol 3-kinase (PI 3-kinase), which suggests that zeta PKC is at least one of the critical targets of PI 3-kinase-triggered signals, and strengthens its role in cell proliferation. PI 3-kinase has been shown, like Raf, to be a direct effector of Ras. zeta PKC is a required step for Ras mitogenic signaling. Therefore, it is possible that zeta PKC directly interacts with Ras during mitogenic activation. We demonstrate here that Ras interacts in vitro with the regulatory domain of zeta PKC as well as that the association of zeta PKC with Ras in vivo is triggered by platelet-derived growth factor. It is also shown here that the expression of a dominant negative mutant of Ras (Asn-17) severely impairs the activation of zeta PKC in mouse fibroblasts. PMID- 7989345 TI - Cloning and expression of myelin-associated oligodendrocytic basic protein. A novel basic protein constituting the central nervous system myelin. AB - We have screened genes predominantly expressed in the rat spinal cord, and we report here cloning of the most abundant unknown gene. It is a novel member of the central nervous system (CNS) myelin-constituting proteins, myelin-associated oligodendrocytic basic protein (MOBP). MOBP is abundantly expressed specifically in oligodendrocytes at the mRNA level only next to myelin basic protein (MBP) and proteolipid protein. Two isoforms have been confirmed. One of them has proline rich tandem repeats and has 84% homology with human counterpart in terms of predicted amino acid sequences. The cDNA-derived primary structure predicts a small, soluble, basic protein. The immunoelectron microscopy has shown that MOBP is expressed throughout compact myelin. All these characteristics are similar to MBP. One definite difference between MBP and MOBP is that MOBP is expressed exclusively in the CNS myelin. These findings suggest that MOBP shares some important functions with MBP in the CNS myelin such as myelin compaction. PMID- 7989346 TI - Vaccinia topoisomerase binds circumferentially to DNA. AB - Vaccinia DNA topoisomerase, a member of the eukaryotic type I enzyme family, binds duplex DNA and forms a covalent adduct at sites containing a conserved sequence element 5'-CCCTT decreases in the scissile strand. The protein-DNA interface entails essential contacts with four phosphate moieties within the CCCTT motif, including the scissile phosphate, and three phosphates within the GGGAA sequence on the noncleaved strand. Critical protein-phosphate contacts are arrayed across the minor groove of the DNA helix. Base-specific contacts with the pentamer element are within the major groove and are situated on the opposite face of the helix. Thus, vaccinia topoisomerase binds circumferentially to its target site in duplex DNA. This binding mode suggests that the eukaryotic enzyme adopts a toroidal shape in the DNA-bound state. Conformational isomerization of the bound protein provides a plausible mechanism for DNA relaxation. PMID- 7989347 TI - Nuclear translocation and anchorage of the growth hormone receptor. AB - The extracellular domain of the rabbit growth hormone (GH) receptor has previously been shown to be associated with the nucleus. However, in this species the GH binding protein (BP) is derived by proteolytic cleavage of the full-length receptor, and thus distinction between the receptor and BP is difficult. The intracellular domain of the GH receptor is required for GH-stimulated function. Thus a direct nuclear function of GH would presumably require the receptor intracellular domain in the nucleus. We have therefore characterized the rat nuclear GH receptor and BP based on their distinct antigenic identity. We show, in vivo, that the full-length receptor is associated with the nucleus, including the respective subnuclear fractions (nucleoplasm, outer nuclear membranes, inner nuclear membranes, and chromatin). In vivo, the receptor is also subject to ligand-dependent nuclear translocation. Cellular transfection of rat GH receptor cDNA resulted in the appearance of nuclear binding sites for 125I-labeled human GH not present in the untransfected parental cell line (Chinese hamster ovary (CHO), buffalo rat liver). To determine which portion of the receptor was responsible for nuclear anchorage, we examined the binding of 125I-labeled human GH to whole nuclei isolated from CHO cells expressing the full-length receptor, a receptor in which 184 amino acids had been deleted from the carboxyl-terminal intracellular domain (CHO-454) and a receptor containing only 5 of 349 amino acids in the intracellular domain (CHO-294). Nuclear binding above the level of the untransfected parental cell line was detected only in CHO-638 and CHO-454 cells, suggesting that amino acids 294-454 of the receptor are necessary for nuclear anchorage. This observation was not due to membrane contamination, as the CHO-294 cells express a membrane-bound receptor that was not anchored in the nucleus. The full-length GH receptor in receptor cDNA-transfected cells is nucleocytoplasmic in the absence of ligand but is also subject to rapid ligand dependent nuclear translocation. The presence of the intracellular domain of the GH receptor in the nucleus allows the possibility of a direct nuclear response to GH. PMID- 7989348 TI - A carboxyl-terminal fragment of lipoprotein lipase binds to the low density lipoprotein receptor-related protein and inhibits lipase-mediated uptake of lipoprotein in cells. AB - It has previously been shown that lipoprotein lipase can mediate uptake of remnant lipoprotein particles via binding to the low density lipoprotein receptor related protein/alpha 2-macroglobulin receptor (LRP). Binding of lipoprotein lipase, and of triglyceride-rich lipoproteins associated with the lipase, to LRP depends on an intact carboxyl-terminal folding domain of the lipase (Nykjaer, A., Bengtsson-Olivecrona, G., Lookene, A., Moestrup, S. K., Petersen, C. M., Weber, W., Beisiegel, W., and Gliemann, J. (1993) J. Biol. Chem. 268, 15048-15055). Here we show that the site for binding to the receptor is within residues 380-425 of the bovine and residues 378-423 of the human lipoprotein lipase. We demonstrate that a carboxyl-terminal fragment of human lipoprotein lipase (residues 378-448), expressed as fusion protein in Escherichia coli, binds to purified and cellular LRP but not to lipoproteins. Binding of the fragment to purified LRP was blocked by heparin. In addition, the fragment inhibited the binding of lipase and the lipase-mediated binding of lipoproteins to the purified receptor. The fragment exhibited reduced binding to proteoglycan-deficient cells. Moreover, the fragment inhibited the uptake of lipoproteins in cells mediated by the lipase via binding to heparan sulfate proteoglycans and LRP. We conclude that the fragment contains the site for binding to LRP and a candidate site for interaction with heparan sulfate proteoglycans, whereas binding to lipoproteins is inefficient. The fragment can therefore inhibit the lipase-mediated lipoprotein uptake, a process that may promote the development of atherosclerosis when occurring in cells of the arterial wall. PMID- 7989349 TI - Cooperative binding of androgen receptors to two DNA sequences is required for androgen induction of the probasin gene. AB - The functional and structural interactions of two androgen receptor-binding sites in the 5'-flanking DNA of the rat probasin gene were determined. Deletion mapping and DNase I footprinting analysis had previously identified two androgen receptor binding sites (ARBS) necessary for androgen induction of the probasin gene: ARBS 1, which resembled a glucocorticoid-responsive element, and ARBS-2, which had a unique sequence. In this study, maximal androgen induction in transient transfection studies only occurred when both sites were present. Neither binding site functioned independently, and deletion of the DNA sequence between the sites resulted in a 60% loss of androgen inducibility. Moreover, point mutations in either ARBS-1 or ARBS-2 led to > 90% loss in activity. Scatchard analysis indicated that ARBS-1 and ARBS-2 bound a synthetic androgen receptor, AR2, with Kd values of 20.0 and 6.7 nM, respectively. Consistent with the higher affinity, ARBS-2 bound AR2 at half the threshold concentration (200 ng) of that required in reciprocal DNase I footprinting experiments with ARBS-1. By comparison, protection occurred at a much lower threshold concentration of AR2 (60 ng) and to the same extent over each site when both sites were present, suggesting a cooperative interaction between the two sites. The cooperative effect was further substantiated when a point mutation in ARBS-1 blocked AR2 binding not only to ARBS-1, but also to ARBS-2. Similarly, a point mutation in ARBS-2 also prevented receptor binding to both sites. Androgen-specific regulation of probasin gene transcription therefore required an androgen-responsive region (positions -286 and +28) containing two androgen receptor-binding sites, where the binding of the androgen receptor to both sites occurred in a cooperative, mutually dependent manner. PMID- 7989350 TI - An adherens junction protein is a member of the family of lactose-binding lectins. AB - We previously described a pig junction protein of M(r) 37,000 found in oral epithelium but not in epidermis, limited to suprabasal cells, and colocalizing by immunofluorescence with adherens junction proteins. A 1.1-kilobase pair cDNA of the 37-kDa protein yielded an open reading frame encoding a 323-amino acid protein of 35,852 Da, and Northern analysis demonstrated a band of 1.2 kilobases in tongue RNA. Secondary structure predictions indicate that the 37% identical 16 17-kDa N- and C-terminal domains from beta-sheet-rich barrels linked by a compact proline-rich segment. The protein is 72% identical in amino acid sequence and shares symmetrical two-domain structure with L-36, a lectin of unknown function from rat intestine, indicating that the 37-kDa protein is the porcine form of L 36. Of the homologous lactose binding lectins known, two others, invertebrate lectins, share this symmetrical structure. Expression of the C-terminal domain of the pig lectin in bacteria yields a lectin which binds lactosyl-Sepharose, and binding is inhibited by lactose. The expressed protein binds a glycoprotein of 120 kDa from pig tongue epithelium on Western blots, and this is also inhibited by lactose. The findings suggest that the lectin function may be involved in the assembly of adherens junctions. PMID- 7989351 TI - Molecular characterization of the 77-kDa echinoderm microtubule-associated protein. Homology to the beta-transducin family. AB - The major microtubule-associated protein (MAP) of sea urchins and several other echinoderms is a polypeptide of M(r) 77,000. The echinoderm MAP (EMAP) is abundant in embryonic and differentiated cells, as well as in mitotic and interphase microtubule arrays. To characterize the molecular structure and function of the EMAP, we isolated a full-length cDNA clone, which has one open reading frame that predicts a polypeptide of 686 amino acids with a calculated M(r) of 75,488. On the basis of charge distribution, EMAP can be divided into two distinctive domains: The NH2-terminal basic region (amino acids 1-137, pI = 10.0) and a slightly acidic, COOH-terminal region (amino acids 138-686, pI = 5.8). This charge distribution is typical of many microtubule-binding proteins, but no significant sequence homology has been detected with any known MAPs. The EMAP, however, does show significant sequence similarity with the beta-subunit of the heterotrimeric G-protein, transducin. The homology lies in a series of 10 imperfect, 43-amino acid repeats (WD-40 repeats) that have been found in many proteins of diverse functions, including beta-transducins, Drosophila Enhancer of split, the yeast STE4, CDC4, CDC20, PRP4, and Tup1 gene products, and the dTAFII80 subunit of Drosophila TFIID. The function of these repeats still remains unknown. It is possible that these repeats are involved in protein-protein interactions, perhaps with the tetratricopeptide repeat-containing protein family. Alternatively, the EMAP may be an important link between signal transduction events and a change in microtubule organization during the cell cycle. PMID- 7989352 TI - Solution structure of Taxotere-induced microtubules to 3-nm resolution. The change in protofilament number is linked to the binding of the taxol side chain. AB - The synchrotron x-ray solution scattering profiles of microtubules assembled from purified GDP- or GTP-tubulin with the antitumor drug docetaxel (Taxotere) are consistent with identical non-globular alpha and beta-tubulin monomers ordered within the known surface lattice of microtubules, with a center to center lateral spacing of 5.7 +/- 0.1 nm. The higher angle part of the scattering profile, and therefore the substructure of the microtubule wall is identical in Taxotere- and Taxol-induced microtubules, to the resolution of the measurements. However, Taxotere-induced microtubules have a mean diameter of 24.2 +/- 0.4 nm, which is 1.12 +/- 0.01 times larger than that of paclitaxel (Taxol) induced microtubules. The population of Taxotere microtubules has on average 13.4 protofilaments, which is similar to control microtubules assembled with glycerol but is in marked contrast with Taxol-induced microtubules, which have on average 12 protofilaments under identical solution conditions. Model populations of Taxotere and Taxol microtubules with the distributions of protofilament numbers determined by electron microscopy reproduce the positions and approximate intensities of the experimental x-ray scattering data. Comparison of the structures and activities of both taxoids strongly suggests that the change of the more frequent lateral bond angle between tubulin molecules from 152.3 degrees (13-protofilament microtubules) to 150 degrees (12-protofilament microtubules) is linked to the binding of the side chain of Taxol. Optimal microtubule formation is obtained with unitary Taxotere to tubulin heterodimer ratio; however, ligand molecules in excess over tubulin dimers cause a loss of cylindrical scattering features, consistent with microtubule opening. The results are compatible with the observed biochemical and thermodynamic properties of this ligand-induced microtubule assembly system and also with the simple working hypothesis that taxoids would bind between adjacent microtubule protofilaments. PMID- 7989353 TI - Evidence that cell surface beta 1,4-galactosyltransferase spontaneously galactosylates an underlying laminin substrate during fibroblast migration. AB - beta 1,4-Galactosyltransferase is unusual among the glycosyltransferases in that a subpopulation exists on the cell surface in addition to its traditional biosynthetic location within the Golgi complex. On the cell surface, galactosyltransferase is expressed in spatially restricted, cell type-specific domains, where it functions as a receptor for extracellular oligosaccharide ligands during selected cellular interactions. For example, galactosyltransferase is found on the leading and trailing edges of migrating cells, where it facilitates lamellipodia formation and cell spreading by binding to specific N linked oligosaccharides within laminin. Although the ability of galactosyltransferase to serve as a laminin receptor is well documented, it is unclear whether it functions solely in a lectin-like capacity to bind laminin glycoside ligands or uses its intrinsic catalytic activity to release itself from and modify its oligosaccharide substrate. In this study, we determined whether cell surface galactosyltransferase spontaneously galactosylates laminin matrices during cell migration using endogenous galactose donors. Cells were prelabeled with [3H]galactose, washed, and transferred in small clusters onto laminin matrices. The prelabeled cells migrated out from the cell cluster, during which time they deposited covalently bound [3H]galactose residues onto the laminin matrix. The degree of galactosylation was both laminin- and time-dependent and required actively migrating, intact cells. The radioactivity released from the 3H galactosylated laminin by acid hydrolysis comigrated with authentic galactose standards on paper chromatography. In parallel assays, there was no radioactivity deposited on laminin matrices when cells were prelabeled with [3H]fucose or [3H]leucine. Furthermore, [3H]galactosylation was dependent upon galactosyltransferase-mediated cell migration, since prelabeled cells did not deposit [3H]galactose when migrating on fibronectin, upon which migration is integrin-dependent and galactosyltransferase-independent. These results raise the possibility that galactosyltransferase functions catalytically during cell migration, either to dissociate from its oligosaccharide ligand and/or to modify the extracellular matrix. PMID- 7989354 TI - Purification of a human polyribosome-associated 3' to 5' exoribonuclease. AB - In cells and cell-free extracts, the early steps in histone mRNA decay occur at the 3' terminus and appear to be catalyzed by a polysome-associated 3' to 5' exoribonuclease. We describe the purification of a polysomal 3' to 5' exoribonuclease that is magnesium-dependent, active at pH 7-8 in salt concentrations below 200 mM, and resistant to the inhibitor of the RNase A family of RNases. The purified enzyme is inactive with 3'-phosphorylated RNA substrates and with DNA but can degrade duplex RNA in the absence of added ATP. The enzyme migrates at approximately 37 kDa by native state gel filtration and at 33 kDa in a SDS-polyacrylamide gel. It degrades poly(A) but not a complex of poly(A) with poly(A) binding protein, and it accelerates histone mRNA decay in high salt washed (enzyme-depleted) polysomes. Similarities between the purified exoribonuclease and the activity that degrades histone mRNA in vitro suggest that the enzyme might be a mammalian messenger ribonuclease. PMID- 7989355 TI - The carboxyl terminus of bradykinin and amino terminus of the light chain of kininogens comprise an endothelial cell binding domain. AB - Bradykinin (BK), a potent vasoactive nonapeptide formed by proteolytic cleavage of kininogen, mediates its activity by binding to specific cell surface receptors. Delivery of BK to these receptors is limited by cell-bound and plasma kininases that degrade BK to inactive fragments. Binding of its parent compound, kininogen, to specific endothelial cell receptors may provide an environment in which the degradation of BK by kininases is restricted. The determinants that mediate kininogen binding to endothelial cells have not been fully elucidated. The present studies suggest that part of BK and the amino-terminal amino acids of kininogens' common light chain constitute part of this recognition sequence. Human umbilical vein endothelial cells (HUVEC) in culture at 37 degrees C express 2-3-fold more binding sites for biotinylated high molecular weight kininogen (biotin-HK) containing BK than for biotin-HK from which BK has been liberated by plasma kallikrein. Binding of BK-free biotin-HK was not restored by preincubating HUVEC with BK, arguing against the possibility that BK released from biotin-HK stimulated expression of additional HK receptors. The extent of biotin-HK binding to HUVEC at 37 degrees C directly correlated with the amount of BK retained within the protein. Four lines of evidence suggest that part of BK and the amino terminus of the light chain of kininogens are part of the sequence recognized by the endothelial cell kininogen receptor. First, monoclonal antibodies to the carboxyl terminus of BK (MBK3) and the common light chains of the kininogens (HKL6, HKL8) inhibited biotin-HK binding to HUVEC. Second, a synthetic, dimeric bradykinin receptor antagonist blocked biotin-HK (IC50 = 9 microM) binding to HUVEC as did two synthetic tissue kallikrein inhibitors modeled after the carboxyl-terminal sequence of BK. Third, synthetic peptides containing the carboxyl-terminal portion of BK and the amino terminus of kininogens' common light chain, MKRPPGFSPFRSSRIG and GFSPFRSSRIG, blocked binding of biotin-HK (IC50 = 2-3 mM), whereas an overlapping peptide, SPFRSSRIGEIKEETT, at 5 mM and a scrambled peptide, FSGPKRSPIMGRPSFR, did not. Fourth, biotinylated GMKRPPGFSPFRSSRIG specifically bound to HUVEC, and its binding was blocked by HK. Since the presence of the nonapeptide BK in HK contributes to maximal binding of HK to HUVEC, there is a novel type of BK receptor in which part of the nonapeptide is recognized within the context of its parent molecule.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 7989356 TI - Furin activates Pseudomonas exotoxin A by specific cleavage in vivo and in vitro. AB - We have demonstrated that the native proenzymatic form of Pseudomonas exotoxin A can be cleaved at its specific activation site by furin in intact Chinese hamster ovary cells or in vitro by furin in isolated membrane fractions from these cells. We have compared the activity of furin in cell membrane fractions with that of purified, recombinant human furin. We have verified that RPE.40, a Pseudomonas toxin-resistant mutant cell strain, is mutant in the fur gene, and we have demonstrated that these cells are deficient in cleavage of the toxin. We have also determined that this cleavage of Pseudomonas toxin by furin takes place at the authentic activation site to release the 37-kDa active fragment. PMID- 7989357 TI - Sperm from mice carrying a targeted mutation of the acrosin gene can penetrate the oocyte zona pellucida and effect fertilization. AB - The physiological function of mammalian sperm acrosin has long been believed to be involved in the limited proteolysis of the oocyte zona pellucida, thus enabling the sperm to penetrate this extracellular matrix and to gain access to the oocyte plasma membrane. Here we show that male mice homozygous for a targeted mutation in the mouse acrosin gene are still fertile in spite of the complete absence of acrosin protease activity in the sperm. In vitro fertilization assays verified that sperm from the homozygous mutant mice penetrate the zona pellucida and effect fertilization. Therefore, acrosin is not essential for both sperm penetration of the zona pellucida and fertilization. PMID- 7989358 TI - Regulation of mRNA encoding 5-HT2A receptors in P11 cells through a post transcriptional mechanism requiring activation of protein kinase C. AB - Exposure of P11 cells to serotonin (5-HT) resulted in a transient increase in levels of 5-HT2A receptor mRNA. Exposure to 5-HT for as short a time as 1 min was sufficient to trigger a delayed increase in receptor mRNA. 5-HT-induced increases in receptor mRNA levels were not antagonized by the protein synthesis inhibitor cycloheximide. The increase in receptor mRNA levels was accompanied by a transient increase in the half-life of receptor mRNA; the rate of transcription of receptor mRNA was unchanged. Submaximal stimulation of phosphinositide hydrolysis by partial agonists or 6-fluoronorepinephrine, an alpha 1-adrenergic receptor agonist, also increased receptor mRNA levels. Exposure to phorbol 12 myristate 13-acetate (PMA), an activator of protein kinase C, mimicked these effects, whereas the protein kinase C inhibitor bisindolylmaleimide antagonized the effects of both 5-HT and PMA. When agonist-promoted increases in receptor mRNA were prevented, the rate of agonist-induced down-regulation was accelerated. These data suggest that levels of 5-HT2A receptor mRNA are regulated by phospholipase C-coupled receptors via a protein kinase C-dependent, post transcriptional mechanism and indicate that agonist-promoted increases in levels of 5-HT2A receptor mRNA modulate receptor expression. PMID- 7989359 TI - Analysis of repair of cyclobutane pyrimidine dimers and pyrimidine 6-4 pyrimidone photoproducts in transcriptionally active and inactive genes in Chinese hamster cells. AB - Irradiation of cells with short wave ultraviolet light (UV-C) induces both cyclobutane pyrimidine dimers (CPD) as well as pyrimidine 6-4 pyrimidone photoproducts (6-4 PP). We have focused on the removal of both types of DNA photolesions from the transcriptionally active adenine phosphoribosyltransferase (APRT) and hypoxanthine-guanine phosphoribosyltransferase (HPRT) genes and the inactive c-mos gene. Induction levels of both CPD and 6-4 PP were similar for all three genes analyzed, with the induction of 6-4 PP being about 3-fold lower than of CPD. Repair of CPD was analyzed using the CPD-specific enzyme T4 endonuclease V; repair of 6-4 PP was examined employing Escherichia coli UvrABC excinuclease. Unlike the HPRT gene, in which CPD were removed selectively from the transcribed strand, both strands of the 16-kilobase fragment encompassing the 2.6-kilobase APRT gene were repaired efficiently. This suggests the existence of multiple transcription units in the APRT region including transcription units running in the opposite direction of the APRT gene. Only a marginal part of the CPD was removed from the inactive c-mos gene after 24 h. In all three genes investigated, 6-4 PP were repaired more rapidly than CPD and, as demonstrated for the HPRT and APRT genes, without strand specificity. The difference in the repair phenotype of CPD between the HPRT gene and the APRT gene coincides with differences between both genes with regard to the DNA strand distribution of previously published UV induced mutations. PMID- 7989360 TI - Generation of the soluble transferrin receptor requires cycling through an endosomal compartment. AB - The transmembrane protein, transferrin receptor (TfR), is found in a soluble form in human serum and in the medium of cell lines grown in tissue culture. The soluble form is generated by proteolytic cleavage between Arg-100 and Leu-101. We used two mutant human TfRs expressed in Chinese hamster ovary (CHO) cells lacking endogenous transferrin receptor to characterize the protease that cleaves the TfR and determine its location in the cell. The T104D mutant TfR lacks the O-linked carbohydrate at position 104, and is more susceptible to proteolytic cleavage at Arg-100 than the wildtype human TfR in these cells. We find that the protease is not a component of the serum in the growth medium, and it is not secreted by the cells. Cleavage does not occur during biosynthesis of the TfR, and occurs after the TfR has reached the cell surface. Expression of the T104D TfR in a temperature-sensitive acidification defective CHO cell line, G.7.1, shows that cleavage of the TfR is not dependent on acidification of endosomes. The C20A23 TfR is an endocytosis deficient mutant lacking an internalization signal. This mutant TfR, which is mainly localized to the cell surface, is cleaved less efficiently than the wild-type TfR, indicating that the protease is localized to an intracellular compartment. PMID- 7989361 TI - The mechanism of inactivation of human factor V and human factor Va by activated protein C. AB - The cleavage of human factor V and human factor Va by human activated protein C (APC) was analyzed in the absence and presence of phospholipid vesicles containing 75% phosphatidylcholine (PC) and 25% phosphatidylserine (PS). Membrane bound human factor V (250 nM) is cleaved by APC (2.5 nM) to give M(r) = 200,000, 70,000, 45,000, and 30,000 fragments and an M(r) = 22/20,000 doublet. These fragments are released after four sequential cleavages of the membrane-bound procofactor at Arg306, Arg506, Arg679, and Lys994. No cofactor activity is observed following thrombin treatment of the membrane-bound APC-cleaved procofactor. In the absence of a membrane surface, no cleavage of factor V by APC is observed, and following thrombin activation factor Va retains full cofactor activity. Membrane-bound human factor Va (600 nM) loses more than 90% of its initial cofactor activity after 10 min of incubation with APC (10.9 nM), and virtually no cofactor activity is observed after 1 h of incubation. Under similar conditions but in the absence of PCPS vesicles, factor Va is cleaved but retains approximately 80% of its initial cofactor activity after 2 h of incubation with APC. In the presence of PCPS vesicles, the APC related loss of activity is correlated with cleavage of the heavy chain and appearance of fragments of M(r) = 45,000, 30,000, and of 28/26,000, and 22/20,000 doublets. These products correspond to three cleavages of the heavy chain (at Arg306, Arg506, and Arg679). Cleavage at Arg506 of factor Va precedes and appears to be required for cleavage at Arg306 and Arg679. In the absence of membrane, proteolysis at Arg506 produces an M(r) = 75,000 fragment which corresponds to the NH2-terminal portion of the human factor Va heavy chain (residues 1-506), and a carboxyl-terminal doublet of M(r) = 28/26,000 (residues 507-709) which is cleaved by APC at Arg679 to generate an M(r) = 22/20,000 doublet and an M(r) = 6,000 peptide. No cleavage of the light chain of the human cofactor is observed in the presence or absence of PCPS vesicles following 2 h of incubation with APC. Our data demonstrate that inactivation of human factor V and human factor Va only occurs in the presence of a membrane surface after cleavage at Arg306. However, while this cleavage site is exposed on membrane-bound human factor V, cleavage at Arg506 on the heavy chain of factor Va appears necessary for complete exposure of the cleavage site at Arg306. PMID- 7989362 TI - Distribution of lipid A species between long and short chain lipopolysaccharides isolated from Salmonella, Yersinia, and Escherichia as seen by 252Cf plasma desorption mass spectrometry. AB - Smooth type endotoxins of Salmonella, Yersinia, and Escherichia were fractionated into long and short chain lipopolysaccharides by silica gel chromatography. Lipid A was prepared from the fractions and analyzed by plasma desorption mass spectrometry. Both Yersinia and Salmonella endotoxins had a large proportion of aminoarabinose-containing lipopolysaccharide molecular species that were found to be concentrated in the long chain fraction. In the Escherichia endotoxin, hypoacylated lipopolysaccharides (lacking the tetradecanoate and one of the four hydroxytetradecanoates) were found mostly in the short chain fraction. Possible implications of these results for the lipopolysaccharide biosynthetic pathway and for studies on the influence of sugar chain length on the biological effects of endotoxins are discussed. PMID- 7989363 TI - C1 repressor-mediated DNA looping is involved in C1 autoregulation of bacteriophage P1. AB - C1 repressor is required to repress the lytic functions of a P1 prophage in vivo. Transcription of the c1 gene is autoregulated via the C1-controlled operator Op99a,b which overlaps the promoter of the c1 gene. It is negatively affected by Lxc corepressor and the DNA region upstream of c1, which contains the additional operators Op99c, d, and e. We have explored these effects by constructing a set of lacZ reporter plasmids with Op99a,b and varying parts of the upstream DNA region. Transcription levels were measured in vivo with a two-plasmid system containing the lacZ reporter and a c1+ lxc+ or c1+ lxc- plasmid. Compared to the C1+Lxc-repressed lacZ reporter with all operators present, the basal level of beta-galactosidase activity increases successively when (i) upstream operators were deleted or inactivated, (ii) Lxc corepressor was removed, and (iii) C1 and Lxc were absent. By that means a 2 x 2 x 15-fold stepwise increase in enzyme activity was found. Using electron microscopy to visualize the interaction of C1 repressor with the operators in vitro, looped DNA molecules were observed. Although all operators can participate in C1-mediated DNA looping, loops between Op99a,b and Op99d occurred predominantly. Lxc is not required but increases drastically the frequency of loop formation. The results indicate that C1 mediated DNA looping may be a second element besides Lxc for fine-tuning the autoregulation of c1 transcription. PMID- 7989364 TI - Rab proteins form in vivo complexes with two isoforms of the GDP-dissociation inhibitor protein (GDI). AB - GTPases of the Rab family play a key role in the regulation of vesicular transport in eukaryotic cells. Several accessory proteins that regulate their GDP/GTP cycle as well as their subcellular localization have been identified within the past few years. The best known is Rab3A GDP dissociation inhibitor protein (GDI), originally identified as an inhibitor of GDP dissociation from Rab3A, a Rab protein specifically expressed in neuronal and neuroendocrine cells. Recent studies have pointed out a role of Rab3A GDI as a chaperone of several Rab proteins during their cycling between cytosol and membranes and Rab3A GDI has been considered so far as a general regulator of Rab function. However, cDNAs encoding potential isoforms of this protein, called GDI beta and GDI-2, have been recently isolated. In this study, we have characterized cytosolic Rab protein complexes in various cell types and tissues using Mono Q chromatography. We show that in rat brain and in insulin-secreting RINm5F cells, the majority of Rab proteins are complexed with Rab3A GDI. In contrast, in Chinese hamster ovary cells, they are mainly complexed to a protein that we have identified as GDI beta. In rat liver cytosol, Rab proteins form complexes with both isoforms. We also show that the proportion of Rab proteins complexed with either isoform depends on the relative abundance of Rab3A GDI and GDI beta in the cytosol. These findings suggest that GDI isoforms are either redundant or could be involved in the fine control of Rab function. PMID- 7989365 TI - A highly conserved homologue of bovine neurocalcin in Drosophila melanogaster is a Ca(2+)-binding protein expressed in neuronal tissues. AB - Polymerase chain reaction was used to search for genes encoding recoverin-like proteins in Drosophila melanogaster. We identified a gene that codes for a cognate of bovine neurocalcin; hence, we have named it neurocalcin (nca). A cDNA of nca was isolated and sequenced. The deduced polypeptide product of the cDNA is 22 kDa in size, and its amino acid sequence is 88% identical to that of bovine neurocalcin. This deduced Drosophila neurocalcin (DrosNCa) protein has three putative EF-hands and has a sequence in its NH2 terminus required for fatty acylation. DrosNCa was expressed in Escherichia coli and subsequently purified by phenyl-Sepharose chromatography and Mono Q anion exchange fast protein liquid chromatography. This recombinant protein was capable of binding 45Ca2+ and exhibited Ca(2+)-dependent mobility shifts in both SDS-polyacrylamide gel electrophoresis and native gel electrophoresis. DrosNCa was tritiated when it was coexpressed in E. coli with N-myristoyl transferase in the presence of [3H]myristic acid. The nca transcript was approximately 1 kilobase long, and tissue in situ hybridization showed that this message was present in the brain of adult flies. Antibodies raised against recombinant DrosNCa cross-reacted with rat hippocalcin on an immunoblot but not with bovine recoverin. When immunohistochemical analysis was performed, staining was observed throughout the central nervous system of adult flies, particularly in the neuropil, where neurons synapse. The nca locus maps to or near 76F on the Drosophila third chromosome. PMID- 7989366 TI - Identification of a novel insulin-responsive element in the rat thyrotropin receptor promoter. AB - By transfecting TSH receptor (TSHR)-chloramphenicol acetyltransferase (CAT) chimeras into FRTL-5 thyroid cells in the presence or absence of insulin, we identify an insulin-responsive element (IRE) between -220 and -190 bp of the TSHR 5'-flanking region. The region between -220 and -192 bp is footprinted by nuclear extracts from FRTL-5 cells and, coupled to a heterologous SV40-CAT chimera, an oligonucleotide containing the protected region induces insulin responsiveness in FRTL-5 cells. FRTL-5 cell nuclear extracts form two groups of protein-DNA complexes, A and B, in gel shift assays using an oligonucleotide having the protected sequence; mutation data indicate only the A complexes are increased by exposure of FRTL-5 cells to insulin; TSH can also increase A complex formation, but the TSH action is insulin-dependent. The nuclear factor(s) in FRTL-5 cells that interact with the TSHR IRE are distinct from thyroid transcription factor-2 (TTF-2), the insulin regulatory factor of the thyroglobulin promoter, as evidenced by the absence of competition in gel shift assays; there is no apparent sequence similarity of this region with other known IREs. The IRE is immediately upstream of a thyroid transcription factor-1 (TTF-1) binding site, -189 to -175 bp; mutation of the TTF-1 site causing a loss of TTF-1 activity also causes a loss of insulin responsiveness when the TSHR-CAT chimera at -220 bp is transfected into FRTL-5 cells and an altered IRE footprint by nuclear extracts. The TSHR appears, therefore, to contain a novel IRE whose activity depends at least in part on TTF-1, a thyroid-specific, homeodomain-containing transcription factor important both for thyroid-specific TSHR gene expression and TSH/cAMP autoregulation of the TSHR. PMID- 7989367 TI - Palmitoylation of the alpha 2A-adrenergic receptor. Analysis of the sequence requirements for and the dynamic properties of alpha 2A-adrenergic receptor palmitoylation. AB - Previous studies have demonstrated that the alpha 2A-adrenergic receptor (alpha 2A AR) incorporates [3H]palmitate and that replacement of Cys442 by Ala or Ser eliminates detectable acylation without perturbing coupling to pertussis toxin sensitive GTP-binding proteins (Kennedy, M. E., and Limbird, L. E. (1993) J. Biol. Chem. 268, 8003-8011) or, as shown here, without perturbing agonist dependent receptor phosphorylation, in contrast to the consequences of eliminating beta 2-adrenergic receptor acylation. As a first step in revealing the functional role for this post-translational modification at the alpha 2A AR, we explored sequences in the alpha 2AAR which confer alpha 2AAR acylation and whether or not [3H]palmitoylation of the alpha 2AAR is dynamic. Deletion of the 7 terminal amino acids distal to Cys442 of the alpha 2AAR did not eliminate detectable [3H]palmitoylation of the alpha 2AAR, whereas truncation to Leu441 did, indicating both that Cys442 is the likely site for acylation and that sequences distal to Cys442 are not required for acylation at Cys442. Since mutation of sequences proximal to Cys442 altered overall receptor structure, based on markedly reduced detectable adrenergic receptor binding, proximal motifs required for palmitoylation of the alpha 2AAR could not be explored further. When the turnover of [35S]Met/Cys-labeled alpha 2AAR was compared with the turnover of the [3H]palmitate-labeled alpha 2AAR, it was of interest that agonist treatment accelerated the half-life of decay of the [3H]palmitate-labeled alpha 2AAR without detectable receptor down-regulation, providing evidence that the acylation of the alpha 2AAR may be a dynamic process. PMID- 7989368 TI - Mammalian DNA ligase II is highly homologous with vaccinia DNA ligase. Identification of the DNA ligase II active site for enzyme-adenylate formation. AB - Mammalian cells contain three biochemically distinct DNA ligases. In this report we describe the purification of DNA ligase II to homogeneity from bovine liver nuclei. This enzyme interacts with ATP to form an enzyme-AMP complex, in which the AMP moiety is covalently linked to a lysine residue. An adenylylated peptide from DNA ligase II contains the sequence, Lys-Tyr-Asp-Gly-Glu-Arg, which is homologous to the active site motif conserved in ATP-dependent DNA ligases. The sequences adjacent to this motif in DNA ligase II are different from the comparable sequences in DNA ligase I, demonstrating that these enzymes are encoded by separate genes. The amino acid sequences of 15 DNA ligase II peptides exhibit striking homology (65% overall identity) with vaccinia DNA ligase. These peptides are also homologous (31% overall identity) with the catalytic domain of mammalian DNA ligase I, indicating that the genes encoding DNA ligases I and II probably evolved from a common ancestral gene. Since vaccinia DNA ligase is not required for DNA replication but influences the ability of the virus to survive DNA damage, the homology between this enzyme and DNA ligase II suggests that DNA ligase II may be involved in DNA repair. PMID- 7989369 TI - Further characterization of the NH2-terminal fibrin-binding site on fibronectin. AB - The fibronectin (Fn) monomer contains two major sites of fibrin binding affinity present within the NH2-terminal and COOH-terminal domains; they consist of five (1F1-5F1) and three (10F1-12F1) consecutive type 1 modules, respectively. Recently, we have reported that the fourth and fifth type 1 module pair (4F1.5F1) of the NH2-terminal domain of fibronectin demonstrated fibrin binding ability (Williams, M. J., Phan, I., Harvery, T. S., Rostagno, A., Gold, L. I., and Campbell, I. D. (1994) J. Mol. Biol. 235, 1303-1311). In an attempt to further localize fibrin binding activity and to characterize the nature of the interaction between different type 1 modules of Fn and fibrin, we have tested a range of recombinant proteins and subtilisin generated proteolytic fragments of Fn in an enzyme-linked immunosorbent assay (ELISA) and by fibrin affinity chromatography. Of the recombinant proteins, we found that only the 4F1.5F1 exhibited significant fibrin binding activity, while 1F1, 1F1.2F1, 7F1, and 10F1 had little to no affinity for fibrin. On a molar basis, 4-5 times more 4F1.5F1 than a proteolytic fragment, corresponding to 1F1-5F1 (25.9 kDa) was required to cause 50% inhibition (IC50) of intact biotinylated Fn binding to fibrin in a competitive ELISA. This suggests that all five type 1 modules in tandem engender higher fibrin binding activity than the 4F1.5F1 alone. Furthermore, since fibrin binding activity of the intact Fn molecule was inhibited, by 70-80%, by the 4F1.5F1, the 25.9-kDa fragment, and a MoAb mapped to an epitope on the 4F1.5F1, the fibrin-binding site within the 4F1.5F1 contributes greatly to the non covalent interaction of intact Fn with fibrin. These results provide significant insight into the Fn/fibrin interaction, a major component of the processes of wound repair and fibrin matrix assembly. PMID- 7989370 TI - 3'-->5' exonuclease active site of phi 29 DNA polymerase. Evidence favoring a metal ion-assisted reaction mechanism. AB - The residues forming the 3'-->5' exonuclease active site of phi 29 DNA polymerase, located at the N-terminal conserved motifs Exo I, Exo II and Exo III, have been defined by site-directed mutagenesis (Bernad, A., Blanco, L., Lazaro, J. M., Martin, G., and Salas, M. (1989) Cell 59, 219-228; Soengas, M. S., Esteban, J. A., Lazaro, J. M., Bernad, A., Blasco, M. A., Salas, M., and Blanco, L. (1992) EMBO J. 11, 4227-4237). To understand their catalytic role, the residual exonuclease activity of mutants at these active site residues has been kinetically studied. The critical function of residues Asp12, Glu14, Asp66, and Asp169 is supported by a 10(5)-fold reduction in the exonuclease catalytic rate upon single mutation. Residue Tyr165 seems to play a secondary role in the exonuclease reaction based on the 10(2)-10(3)-fold reduced catalytic rate of mutants Y165F and Y165C. Most of the mutants were specially active in the presence of Mn2+ ions, which could be indicative of a direct involvement of these residues in a metal ion-assisted exonucleolytic reaction. The data obtained strongly suggest that the 3'-->5' exonuclease active site of phi 29 DNA polymerase is structurally and functionally similar to that of the Escherichia coli DNA polymerase I. In addition, these residues were also very important for the strand displacement ability of phi 29 DNA polymerase, suggesting a structural overlapping of this activity with the 3'-->5' exonuclease. PMID- 7989372 TI - Incorporation of 5-fluorouracil into U2 and U6 snRNA inhibits mRNA precursor splicing. AB - The splicing activities of 5-fluorouracil (FUra)-substituted U2 and U6 small nuclear RNAs (snRNAs) were examined in an in vitro splicing system. Yeast splicing extracts were specifically depleted of endogenous U2 and U6 snRNAs by antisense oligonucleotide-directed RNase H hydrolysis. Splicing activity was recovered when the extracts were reconstituted with synthetic U2 and U6 snRNAs. However, U2 snRNA with all uracils substituted with FUra (FU2) did not restore any splicing activity. Nondenaturing gel electrophoresis showed that FU2 failed to promote the assembly of spliceosome complexes. The ability of U2 snRNA to restore splicing in U2-depleted extracts increased as FUra content decreased but was still only 60% of control activity at 25% substitution of uracils with FUra. Addition of FU2 to nondepleted extracts caused strong inhibition of splicing accompanied by increased degradation of the pre-mRNA, suggesting that FU2 forms an inactive complex with a protein splicing factor that normally binds to the pre mRNA. FU6 restored full splicing activity to U6-depleted extracts, but at a 5 fold higher concentration than U6 snRNA. These results demonstrate that the incorporation of FUra can impair the functions of catalytic RNA molecules. PMID- 7989371 TI - Bidirectional regulation of c-fos promoter by an oncogenic gip2 mutant of G alpha i2. A novel implication of retinoblastoma gene product. AB - G alpha i2 is a tissue-specific proto-oncogene product, whose activated mutant gip2 induces transformation through less defined downstream pathways. We found that c-fos promoter is a target of gip2 in multiple kinds of cells. Serum response element was shown to be the positive enhancer element that mediates gip2 induced c-fos expression. We further demonstrated that gip2 stimulates the negative silencer activity of the retinoblastoma (Rb) control element (RCE) and inhibits the c-fos promoter activity through RCE located in the c-fos promoter region. The effect of gip2 on RCE was shown to be mediated by the Rb gene product (pRb). Furthermore, gip2 augmented underphosphorylated active form of pRb by promoting pRb expression and by affecting the phosphorylation state of pRb. gip2 therefore propagates both positive and negative signals to the c-fos promoter through two different elements, and pRb mediates the negative signal of gip2. We conclude that gip2 has bifunctional roles in transformation which pRb critically regulates. Given that Rat-1 cells, which gip2 can transform, lack the sensitivity to the gip2/pRb-mediated negative pathway, this study provides a novel insight into oncogenesis by gip2 and its tissue specificity. PMID- 7989373 TI - Structural analysis of the human hydroxyindole-O-methyltransferase gene. Presence of two distinct promoters. AB - Hydroxyindole-O-methyltransferase (HIOMT) catalyzes the last step in the metabolic pathway that synthesizes the hormone melatonin. We have found HIOMT mRNA present in small amounts in human retina and in relatively high abundance in the pineal gland. Two distinct 5' ends were found in human retina using a solid phase 5'-rapid amplification of cDNA ends technique. The two 5' regions appear to originate from two distinct putative promoters. Although many similarities exist between the two promoters, they contain distinctive elements. Putative promoter A, for example, contains a recently discovered photoreceptor-conserved element (PCE-1, CAATTAAG) at -27 not found in promoter B, while promoter B contains an Ap1 site (ATGAGTCAA) at -166 and an octamer site (ATGCAAT) at -59 not found in promoter A. The HIOMT messages are also alternatively spliced in between exons 6 and 8, generating three distinct messages. One of the alternatively spliced messages contains a line-1 repetitive element that is spliced into the mRNA precisely as exon 6. Importantly, the downstream open reading frame is not altered by any of these splicing combinations. The gene is approximately 35 kilobases long containing either 9 or 10 exons (including the line-1 element) depending on which promoter is active. All of the splice sites follow the GT/AG rule. The dual promoters and opportunities for alternative splicing suggest a variety of mechanisms for control of HIOMT expression and biological activity in different tissues not previously recognized. PMID- 7989374 TI - Insertion and deletion mutants of FokI restriction endonuclease. AB - FokI restriction endonuclease recognizes the nonpalindromic pentadeoxyribonucleotide, 5'-GGATG-3':5'-CATCC-3' in duplex DNA and cleaves 9 and 13 nucleotides away from the recognition site. We have reported the presence of two distinct and separable protein domains within this enzyme: one for the sequence-specific recognition of DNA (the DNA binding domain) and the other for the endonucleases activity (the cleavage domain). Our studies have suggested that the two domains are connected by a linker region, which appears to be amenable for repositioning of the DNA-sequence recognition domain with respect to the catalytic domain. Here, we report the construction of several insertion (4-, 8-, 12-, 18-, 19-, or 23-amino acid residues) and deletion (4- or 7-amino acid residues) mutants of the linker region of FokI endonuclease. The mutant enzymes were purified, and their cleavage properties were characterized. The mutants have the same DNA sequence specificity as the wild-type enzyme. However, compared with the wild-type enzyme, the insertion mutants cleave predominantly one nucleotide further away from the recognition site on both strands of the DNA substrate. The four-codon deletion mutant shows relaxed specificity at the cut site while the seven-codon deletion appears to inactivate the enzyme. The DNA binding and cleavage domains of FokI appear to be linked by a relatively malleable linker. No simple linear relationship exists between the linker length and the distance of the cut site from the recognition site. Furthermore, the four-codon insertion mutants cleave DNA substrates containing hemi-methylated FokI sites; they do not cleave fully methylated substrates. These results are best explained as a consequence of protein-protein interactions between the domains. PMID- 7989375 TI - The 5' enhancer of the mouse mammary tumor virus long terminal repeat contains a functional AP-2 element. AB - The mouse mammary tumor virus (MMTV) retrovirus causes mammary adenocarcinomas in mice by proviral insertion near members of the wnt family of proto-oncogenes, leading to their deregulation and cellular transformation. The 5' end of the MMTV long terminal repeat (LTR) has been implicated in tissue-specific activation of these genes. In this study, we characterize an enhancer element (Ban2; -1075 to 978) at the 5' end of the MMTV LTR. We show that this enhancer is 5-fold more active in a murine mammary carcinoma cell line (34i) than in a fibroblast cell line (NIH3T3), and is inactive in the liver carcinoma cell line HepG2. Mutagenesis of the enhancer reveals four cis-acting elements that are required for maximal activity. DNA-binding proteins that interact with each of the four elements have been identified. One of these factors, designated mp5, is either identical to, or closely related to, the transcription factor AP-2. The mp5/AP-2 DNA binding activity co-migrates with recombinant AP-2 and is supershifted by anti-AP-2 antibodies. We also show that the lack of enhancer activity in HepG2 cells results from the absence of AP-2 protein in these cells. Co-transfection of an AP-2 expression vector restores the activity of this enhancer in HepG2 cells, and requires an intact mp5-binding site. PMID- 7989376 TI - 2',3'-Dialdehyde GTP as an irreversible G protein antagonist. Disruption and reconstitution of G protein-mediated signal transduction in cells and cell membranes. AB - The 2',3'-dialdehyde analogue of GTP, oGTP, was devised as an irreversible antagonist of regulatory GTP-binding proteins (G proteins). Here, we show that oGTP uncouples transmembrane signaling mediated by a set of distinct G proteins both in isolated membranes and in whole cells. In human platelet membranes, pretreatment with oGTP suppressed receptor- and G protein-controlled regulation of adenylyl cyclase activity. In chick neuronal cells, inhibition of the voltage sensitive Ca(2+)-current by various membrane receptors (alpha 2-adrenergic, somatostatin, GABAB) was eliminated when oGTP was applied intracellularly in the whole cell patch-clamp configuration. Disruption of endogenous signaling pathways by oGTP occurred through specific blockage of the GTP-binding site of G protein alpha-subunits by the following criteria: (i) pretreatment of membranes with oGTP blocked direct G protein activation by guanine nucleotides as well as labeling of Gs alpha and Gi alpha with the photoaffinity probe [alpha-32P]GTP azidoanilide. (ii) The effect of oGTP was antagonized by the simultaneous introduction of guanosine 5'-(3-O-thio)triphosphate into the patch-clamped cell. (iii) The time to onset of action was similar for oGTP and guanosine 5'-O-thio)diphosphate. (iv) Inactivation of G protein-dependent signaling was overcome by substituting G protein alpha-subunits. Addition of both the short and long form of recombinant Gs alpha (rGs alpha-s and rGs alpha-L) restored guanine nucleotide-dependent adenylyl cyclase activity to oGTP-treated platelet membranes with rGs alpha-L being approximately 3-10-fold more potent than rGs alpha-s. This apparent preference was due to the intrinsically different activation rates of rGs alpha-L and rGs alpha-s. When reconstituted with exogenous rGs alpha, the A2-adenosine receptor did not discriminate among the two forms of rGs alpha. Thus, Gs alpha-L is the primary determinant of basal cAMP formation in platelets. In contrast, neither the addition of various recombinant subtypes of Gi/o nor purified bovine brain beta gamma-dimers reconstituted adenylyl cyclase inhibition in oGTP-treated membranes. All subtypes of Gi alpha stimulated adenylyl cyclase. In the presence of rGs alpha, a conditional stimulation by beta gamma-dimers was observed. This pattern of stimulation shows that platelet adenylyl cyclase is a type II-like isoform. Either a differently modified G protein or an ancillary GTP-binding component is required for adenylyl cyclase inhibition in platelets. oGTP can be considered a useful tool for disruption and reconstitution of transmembrane signaling mediated by presumably all classes of heterotrimeric G proteins. PMID- 7989377 TI - Structural and functional characterization of the interaction between 2',3' dialdehyde guanine nucleotide analogues and the stimulatory G protein alpha subunit. AB - We have searched for irreversible ligands which target the guanine nucleotide binding pocket of G protein alpha-subunits by testing the ability of periodate oxidized 2',3'-dialdehyde guanine nucleotide analogues of GTP (oGTP) and GTP gamma S (oGTP gamma S) to bind to the recombinant alpha-subunit of the stimulatory G protein, rGs alpha-s. oGTP and oGTP gamma S bind to rGs alpha-s in a quasi-irreversible manner via formation of a Schiff's base, which can be reduced with borhydrid resulting in covalent incorporation of [alpha-32P]oGTP and [35S]oGTP gamma S into rGs alpha-s. When bound to rGs alpha-s, oGTP is hydrolyzed and traps the protein in the inactive conformation, while oGTP gamma S persistently activates rGs alpha. Thus, oGTP and oGTP gamma S act as irreversible G protein antagonist and agonist, respectively, and represent a pair of nucleotide analogues suitable as functional and structural tools. Cleavage of covalently labeled rGs alpha-s with cyanogen bromide generates several labeled fragments. Labeled fragments were assigned to the G1 and G4 region of the guanine nucleotide binding pocket using sequence-specific antisera. An additional, labeled fragment was identified by amino-terminal sequencing and corresponded to the helix alpha A in the recently determined crystal structure of the transducin alpha-subunit (Noel, J. P., Hamm, H. E., and Sigler, P. B. (1993) Nature 366, 654 663). In the oGDP-liganded conformation, incorporation occurs predominantly into the G1-fragment, while [35S]oGTP gamma S labels the additional fragments to a similar extent indicating tight packing around the guanine nucleotide binding pocket in the active conformation. Furthermore, rGs alpha-s contains a single acid cleavable bond (Asp317-Pro318), such that formic acid releases a carboxyl terminal fragment from [alpha-32P]oGTP- and [35S]oGTP gamma S-liganded rGs alpha s. This fragment contains a single lysine residue (Lys324) which is only labeled by [35S]oGTP gamma S. Lys324 is unique to Gs alpha and lies within its effector binding region. Hence, during the switch from the inactive to the active state, this region undergoes a major conformational change that moves it closer to the nucleotide binding pocket. PMID- 7989378 TI - Can a signal sequence become too hydrophobic? AB - We have characterized several mutants that contain alterations in the hydrophilic domain (N region) of the pseudorabies virus glycoprotein gC signal sequence. In general, our results agree with previous findings and indicate that basic residues in the N region are not essential for efficient export of gC in infected cells. While reducing the N region to a net neutral charge led to a slight impairment of membrane translocation, a substantial gC export defect was not observed until a net negative charge was introduced. However, there was one exception to this pattern. The substitution of a leucine for an arginine at the carboxyl terminus of the N region led to a considerable export defect despite maintaining a net positive charge. As a consequence of the substitution, the mutant signal sequence was 1.5 times more hydrophobic than wild type, but we found that the defect could be largely corrected if an additional alteration that lessened the overall hydrophobicity of the gC signal sequence was incorporated. We suggest that an upper limit of hydrophobicity may exist for eukaryotic signal sequences; exceeding this value could lead to an export defect. PMID- 7989380 TI - Religio Medici, 1994. PMID- 7989381 TI - The surgeon's prosthesis. PMID- 7989379 TI - Quantitative analysis of alternative splicing options of human plasma membrane calcium pump genes. PMID- 7989382 TI - Results after replantation and revascularization in the upper extremity in children. AB - The rates of survival of the amputated part and the functional outcomes were studied retrospectively after seventy-three replantations and eighty-nine revascularizations in the upper extremity in 120 children. All operations were performed between January 1974 and December 1988 after partial and complete amputations at various levels. The ages of the patients ranged from three days to sixteen years. The average duration of follow-up was thirty-six months (range, fourteen months to seven years) for the patients who had had a replantation and thirty months (range, fourteen months to eight years) for the patients who had had a revascularization. The rate of survival of the amputated part was significantly higher (p < 0.0002) after revascularization (seventy-eight parts [88 per cent]) than after replantation (forty-six parts [63 per cent]). There was no association, for either group, between survival and the preoperative duration of ischemia, the level of the injury, the digit that had been injured, the number of arteries that had been repaired, or the use of venous grafts. The rate of survival after replantation of completely amputated parts was 72 per cent (twenty eight of thirty-nine parts) when the amputation had resulted from a laceration injury and 53 per cent (eighteen of thirty-four parts) when the amputation had resulted from a crush or an avulsion injury. The rate of survival after revascularization of incompletely amputated parts was 100 per cent (all forty five parts) when the injury had been the result of a laceration and 75 per cent (thirty-three of forty-four parts) when it had been the result of a crush or an avulsion. We did not find any relationship between the age of the patient and the rate of survival of the amputated part after revascularization; however, there was a significantly higher rate of survival (p , 0.02) after replantation in children who were less than nine years old (77 per cent [twenty-four of thirty one parts]) compared with the rate in those who were nine to sixteen years old (52 per cent [twenty-two of forty-two parts]). The viability of the digit was in jeopardy after twenty-nine (40 per cent) of the seventy-three replantations and nineteen (21 per cent) of the eighty-nine revascularizations. Immediate reoperation resulted in the salvage of only two of the twenty-one replanted parts and six of the twelve revascularized parts that had a reoperation.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 7989383 TI - Closed reduction for congenital dysplasia of the hip. Functional and radiographic results after an average of thirty years. AB - The functional and radiographic results of closed reduction in 152 congenitally dislocated hips of 119 patients who had been managed between 1938 and 1969 were reviewed retrospectively. The average age of the patients at the time of the reduction was twenty-one months (range, one to ninety-six months). At the time of the latest follow-up evaluation, the average age was thirty-one years (range, sixteen to fifty-six years). The average duration of follow-up was thirty years (range, fifteen to fifty-three years). At the latest follow-up evaluation, the Iowa hip rating averaged 91 points (range, 38 to 100 points) and the Harris hip score averaged 90 points (range, 33 to 100 points). Thirty-five hips were rated Severin Class I; thirty-five, Class II; twenty-eight, Class III; fifty-three, Class IV; and one, Class VI. Disturbance of growth in the proximal end of the femur occurred in ninety-one hips (60 per cent). Eight contralateral hips that had appeared normal also demonstrated disturbance of proximal femoral growth. In many hips, partial physeal arrest could not be determined for ten to twelve years after the reduction. Seventeen hips (twelve patients) had a total replacement when the patients were an average age of thirty-six years (range, nineteen to fifty-three years). Sixty-five hips (43 per cent) had radiographic evidence of degenerative joint disease. Patients who did not have a growth disturbance of the proximal end of the femur or evidence of subluxation tended to function extremely well for many years despite a radiographic result that was less than anatomical. Function tended to deteriorate with time, even in the absence of disturbance of growth in the proximal end of the femur. Despite generally good function at the latest follow-up evaluation, the prognosis for these patients remained guarded. PMID- 7989384 TI - Intracapsular fractures of the femoral neck. Results of cannulated screw fixation. AB - The results of stabilization of an intracapsular fracture of the femoral neck with cannulated screws placed in parallel in 141 patients between 1980 and 1985 were reviewed retrospectively. Fifty patients (35 per cent) had a non-displaced fracture (Garden Stage I or II) and ninety-one (65 per cent) had a displaced fracture (Garden Stage III or IV). The median age of the patients was sixty-eight years (range, twenty-four to ninety-five years). The mean duration of follow-up was eight years. No patient died or had a wound infection during the stay in the hospital. Twenty-nine patients, who had a median age of seventy-five years (range, fifty-six to ninety-five years), died within sixty months after treatment; eleven of them (median age, seventy-five years [range, sixty-five to eighty-six years]) died within the first twelve months. There was a loss of position or a non-union of the fracture in five patients (4 per cent) and healing of the fracture in 136 patients (96 per cent). Thirteen patients (11 +/- 3 per cent) had histological or roentgenographic evidence of osteonecrosis within twenty-four months after treatment. Ten of these patients had had a displaced fracture. Osteonecrosis developed in thirteen additional patients during the remaining period of follow-up. Eight of these patients had had a displaced fracture. The prevalence of osteonecrosis at the time of the most recent follow up (mean duration, eight years) was 22 +/- 4 per cent. Osteonecrosis developed in eight of the forty-one patients who had had a Garden Stage-II fracture, in six of the thirty patients who had had a Garden Stage-III fracture, and in twelve of the forty patients who had had a Garden Stage-IV fracture. The fifty-five surviving patients in whom the fracture healed without complications were found to be functioning well more than sixty months after the fracture. PMID- 7989385 TI - Ultrasonographic evaluation of the elbow in infants and young children after suspected trauma. AB - Fractures and epiphyseal injuries in the region of the elbow are uncommon in infants and young children, but they can be very difficult to diagnose and delineate accurately. In addition to plain radiography, invasive or costly procedures such as arthrography and magnetic resonance imaging traditionally have been used to evaluate these injuries. We used high-resolution real-time ultrasonography to evaluate a suspected injury of the elbow in seven infants and one ten-year-old child. Three of the infants had a physeal separation, two had a supracondylar fracture, and two had no skeletal injury. The child had an avulsion fracture of the lateral epicondyle of the humerus and an effusion in the joint. The ultrasonographic findings were confirmed by arthrography in three patients, by open reduction in one, and by follow-up radiographs in all. None of the ultrasonographic studies were performed with the patient under general anesthesia. Ultrasonography, a readily available, non-invasive technique, can be used to evaluate the unossified epiphysis about the elbow of infants and young children; to demonstrate dislocations, fractures, and physeal separations; to identify a hinge of soft tissue at the site of a fracture; to identify interposition of soft tissue between fracture fragments; and to aid in the planning of closed and open reductions. PMID- 7989386 TI - Prophylaxis for the prevention of venous thromboembolism after total knee arthroplasty. A comparison between unfractionated and low-molecular-weight heparin. AB - We compared the efficacy and safety of low-molecular-weight heparin with that of low-dose unfractionated heparin in the prevention of venous thromboembolism after total knee arthroplasty in a prospective, randomized, multicenter trial. One hundred and eighty-five patients were randomly assigned to two groups: ninety-two received low-molecular-weight heparin (forty milligrams of enoxaparin the evening before the operation and once a day subsequently) and ninety-three received unfractionated heparin (5000 international units the evening before the operation and three times a day thereafter). The prophylaxis was continued until bilateral ascending venography was performed six to nine days after the operation or, if venography was not done, until the eighth postoperative day. Venography revealed a prevalence of deep-vein thrombosis of 27 per cent (twenty-five of ninety-three patients) in the group that received unfractionated heparin and 23 per cent (twenty-one of ninety-two patients) in the group that received low-molecular weight heparin. The difference was not significant (p = 0.6). Five patients (5 per cent) who received unfractionated heparin and 3 patients (3 per cent) who received low-molecular-weight heparin had a deep-vein thrombosis in the proximal veins. Two patients who received unfractionated heparin and one who received low molecular-weight heparin had clinical symptoms suggestive of a pulmonary embolism. None of these three patients had a positive ventilation-perfusion scan. There were no deaths, major bleeding episodes, or wound hematomas necessitating operative intervention or discontinuation of the anticoagulation in the series.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7989388 TI - Recurrence of giant-cell tumors of the long bones after curettage and packing with cement. AB - The nine-year experience with sixty patients who had had a giant-cell tumor of a long bone was reviewed to determine the rate of recurrence after treatment with curettage and packing with polymethylmethacrylate cement. The demographic characteristics, including the age and sex of the patient and the site of the tumor, were similar to those that have been reported for other large series. An average of four years (range, two to ten years) after the operation, the over-all rate of initial local recurrence was 25 per cent (fifteen of sixty patients). Patients who had had a tumor of the distal aspect of the radius had a higher rate of recurrence (five of ten) than those who had had a tumor of the proximal aspect of the tibia (seven [28 per cent] of twenty-five) or of the distal part of the femur (three [13 per cent] of twenty-three). Higher rates of recurrence were also noted for patients who had had a pathological fracture (three of six), those who had had a Stage-III tumor according to the classification of Campanacci et al. (six of sixteen), and those who had not had adjuvant treatment with either a high speed burr or phenol (eight of nineteen). Patients who had had an initial recurrence after packing with cement had a low rate of secondary recurrence when the initial recurrence had been treated with a wide resection or a second intralesional procedure (zero of ten and one of five patients, respectively), after an average of three years (range, ten months to eight years). No patient had a multicentric tumor or metastasis.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7989387 TI - Biomechanical evaluation of a simulated Bankart lesion. AB - The purpose of this study was to determine the effect of sectioning of the anterior part of the inferior glenohumeral ligament (a simulated Bankart lesion) on load-induced multidirectional glenohumeral motion. Nine fresh, intact cadaveric shoulders were tested on a special apparatus that constrained three rotations but allowed simultaneous measurement of anterior-posterior, superior inferior, and medial-lateral translation. Coupled anterior-posterior and superior posterior translations were recorded while anterior, posterior, superior, and inferior forces of fifty newtons were applied sequentially. Testing was done in three positions of humeral elevation in the scapular plane, in three positions of humeral rotation, and with an externally applied joint-compression load of twenty two newtons. A liquid-metal strain-gauge was placed on the posterior band of the inferior glenohumeral ligament to assess concomitant posterior capsular strain during the various test conditions. All shoulders were tested intact and again after the inferior glenohumeral ligament and the labrum had been detached from the glenoid from just superior to the anterior band of the inferior glenohumeral ligament to a point just posterior to the infraglenoid tubercle. The simulated Bankart lesion resulted in selected increases in anterior translation at all positions of elevation, in posterior translation at 90 degrees of elevation, and in inferior translation at all positions of elevation. However, these increases were very small; the maximum mean increase in translation seen over-all was only 3.4 millimeters, which occurred during inferior translation at 45 degrees of elevation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7989389 TI - Revision of the acetabulum without cement with use of the Harris-Galante porous coated implant. Two to eight-year results. AB - Sixty revision total hip arthroplasties were performed in fifty-nine patients with use of the Harris-Galante-I porous-coated acetabular component. The patients were followed prospectively for a mean of five years (range, two to eight years). Multiple small screws were used for fixation of the component in all of the hips. Bulk allograft or cancellous bone graft was placed in forty-eight hips. The hips were evaluated clinically with use of the Harris hip-scoring system. A component was considered to be loose if there was a change in the cup angle of more than 5 degrees or vertical or horizontal migration of more than two millimeters, as demonstrated on serial radiographs. Forty-eight (80 per cent) of the sixty hips had a score of good or excellent at the time of the most recent follow-up. No component had radiographic evidence of loosening, and there were no broken screws or radio-lucent lines around the screws. Osteolysis of the pelvis was not seen in any patient. One hip was debrided because of a late metastatic deep infection, but the components were not removed. At the time of writing, no acetabular component had been revised and no revisions were pending. There were no complications related to the use of multiple small screws, even in the acetabula in which there was a severe deficiency of bone.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7989390 TI - Increase of motion between lumbar vertebrae after excision of the capsule and cartilage of the facets. A cadaver study. AB - Seventeen fresh segments of cadaveric lumbar spines were tested in flexion, extension, and axial rotation. The resulting angular rotations were measured with the use of a goniometer and a three-dimensional system of video analysis. Measurements of flexibility were made, in order, in the intact spine; after decompression (bilateral total laminectomies, partial medial facetectomies, and foraminotomies); after excision of the capsule and cartilage of the facets; and after cancellous bone had been packed into the facet defects. Decompression resulted in a slight increase in the sagittal and axial ranges of motion. Subsequent excision of the capsule and cartilage of the facets, as in preparation for an arthrodesis of the facets, resulted in a significant increase in both the sagittal (5.7 +/- 2.9 degrees, mean and standard deviation) (p < 0.001) and the axial (1.4 +/- 0.9 degrees) (p < 0.01) ranges of motion compared with the motion in the intact specimen and with the motion in the specimen after only decompression had been done (p < 0.01 and p < 0.05, respectively). Packing of bone in the facets did not significantly reduce motion. It was calculated that the increase in the sagittal range of motion after excision of the capsule and cartilage of the facets would increase the tensile strain in a graft between the transverse processes of the fourth and fifth lumbar vertebrae (18 +/- 1 per cent tensile strain [mean and 95 per cent confidence interval] for the intact vertebrae and 25 +/- 1 per cent for the vertebrae in which the facets had been excised). PMID- 7989391 TI - Extensive deep venous thrombosis resulting in compartment syndrome of the thigh and leg. A case report. PMID- 7989392 TI - Cat-scratch disease presenting as a paravertebral abscess. A case report. PMID- 7989393 TI - Phalangeal transfer for recurrent giant-cell tumor of the phalanx of a finger in a nine-year-old child. A case report with forty-one-year follow-up. PMID- 7989394 TI - Fractures about the knee in children. PMID- 7989395 TI - Current concepts in orthopaedic biomaterials and implant fixation. PMID- 7989396 TI - Graph theory and group contributions in the estimation of boiling points. AB - Estimation of normal boiling points of organic compounds using a group contribution method is known to be unsatisfactory and an attempt has been made to improve the accuracy of the estimations by including chemical graph information in the regressions. This leads to a measurable improvement in the results obtained for both a set of 63 alcohols and also a set of 541 structurally diverse organic compounds. This new approach was found to have better predictive ability than the group contribution approach both in the cross-validation tests and in predicting the normal boiling points for 32 new compounds. PMID- 7989397 TI - META. 1. A program for the evaluation of metabolic transformation of chemicals. AB - A new metabolism program, META, is introduced. In this paper, the basic principles on which the program operates are described. META is an expert system, capable of predicting the sites of potential enzymatic attack and the nature of the chemicals formed by such metabolic transformations. It operates from dictionaries of transformation operators, created by experts to represent known metabolic paths. PMID- 7989398 TI - META. 2. A dictionary model of mammalian xenobiotic metabolism. AB - META is a new knowledge-based expert system that provides computer simulation of the biotransformation of chemicals. The program is based on the recognition of key functional groups within the complete chemical structure and therefore can predict the metabolites of new xenobiotics. Here, we describe a comprehensive knowledge base built for the purposes of modeling mammalian metabolism with META methodology. PMID- 7989399 TI - Many cultures/more compassion. PMID- 7989400 TI - Steroids in multiple sclerosis. AB - Steroids are widely used in treating the relapse of multiple sclerosis. There is no place for long term steroid therapy of this disease. Current practice is a short course of high dose methylprednisolone which can be repeated after an interval, has proven safety and objectively accelerates recovery. PMID- 7989401 TI - Efficient phosphate binding using a combination of gluconolactate and carbonate calcium salts. AB - Although renal-failure-related hyperphosphataemia can be corrected by various phosphate binders, there remains a need for safer and more efficient formulations to precipitate phosphate. This work describes both a theoretical approach and a phosphate precipitation test in order to design efficient binding calcium salts formulations. The results show that the combination of a soluble calcium salt (the gluconolactate) and a proton-consuming calcium salt (the carbonate) can precipitate phosphate effectively. Furthermore, the theoretical computations correlate well with the ability of the salt to bind phosphate in vitro. PMID- 7989402 TI - Oral chloral hydrate provides effective and safe sedation in paediatric magnetic resonance imaging. AB - Sedation is routinely required for successful Magnetic Resonance imaging in infants and children. Five hundred and ninety-six paediatric patients (270 female and 326 male, age (mean +/- SD) 41 +/- 30 months and weight 14.8 +/- 6.5 kg) entered an open, non-comparative, prospective study to assess oral chloral hydrate sedation in a large and homogeneous paediatric population undergoing Magnetic Resonance imaging. Chloral hydrate syrup 70 mg/ml was administered 20-40 min prior to the procedure. Effective sedation was reached in 94.1% with a total dose (mean +/- SEM) of 68 +/- 1 mg/kg (range 20-170 mg/kg). Statistical analysis of sedation failures vs. successful examinations after the total dose showed significant differences for dose (62 +/- 4 vs. 69 +/- 1 mg/kg; P < 0.05), age (64 +/- 7 vs. 40 +/- 1 months; P < 0.001) and weight (19.8 +/- 1.5 vs. 14.5 +/- 0.0 kg; P < 0.001). Effectiveness fell to around 80% in children with encephalic white matter alterations, medullary tumours or syringohydromyela (P = 0.07). The mean time of onset of sedation was 26 +/- 1 min, and the mean time to spontaneous awakening after the completion of the Magnetic Resonance examination was 38 +/- 2 min. Fifty-nine children (9.9%) experienced adverse reactions, with nausea and vomiting being the most common (n = 41), followed by nervousness and unusual excitement (n = 6). Discriminant function analysis identified age and total dose as the quantitative variables helping to differentiate between sedation failures and satisfactory examinations (sensitivity = 0.73, and specificity = 0.61; r = 0.20, P < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7989403 TI - Pharmacokinetics of phenytoin in routine clinic patients in Malaysia. AB - We estimated individual and population Michaelis-Menten pharmacokinetic parameters for phenytoin (DPH) in epileptic patients attending our neurology clinic using the computer programme. OPT. Our results agreed well with literature values but were lower than those we obtained earlier in a smaller number of patients. The Km was independent of age, weight and sex but there was a weak, correlation between Vm and body weight. We conclude that the use of population Vm and Km in normograms could lead to errors in DPH dose estimations as they correlated very poorly with patient characteristics. OPT was easy to use and sufficiently accurate for deriving dose estimates in routine patients. Its use would enable practitioners to generate their patients' own parameters for use in individual dosage adjustments. The estimates can subsequently be updated as more data become available. PMID- 7989404 TI - Enhancement of microbiological safety levels of aseptically admixed total parenteral nutrition solutions through low-dose gamma irradiation. AB - This study was undertaken to determine the effect of low-dose gamma irradiation on aseptically admixed total parenteral nutrition (TPN) solutions to which large inocula of three test bacterial species were added. Microbiological safety levels were quantified in terms of sterility assurance levels (SALs), indicating the probability of contamination occurring expressed as 10-n. The radiation sensitivity (D10 values) of test bacteria in TPN solutions inoculated with a series of bacteria recognized as common contaminants of these products, was determined. Attainable SALs of TPN solutions containing test bacteria were subsequently calculated from the D10 values. Results showed that a minimum absorbed radiation dose as low as 1.5 kGy improved the SAL of aseptically prepared TPN solutions from a probability value of 10(-3) to a value of less than 10(-8) for the microorganisms investigated. At an absorbed dose as high as 8.3 kGy, no measurable changes in amino acid, electrolyte, glucose and lipid components of the solutions were detected. These findings have important implications for the enhancement of microbiological safety levels of aseptically prepared intravenous fluids in general. PMID- 7989405 TI - Lack of a pharmacokinetic interaction between ciprofloxacin and fenbufen. AB - The possible effects of a three day pretreatment with fenbufen on the pharmacokinetics of a single oral (500 mg) dose of ciprofloxacin were evaluated in a randomized crossover study in a group of eight healthy male volunteers. Fenbufen pretreatment was shown to have no significant effect on ciprofloxacin pharmacokinetics. PMID- 7989406 TI - Stability of ciprofloxacin in 5% dextrose and normal saline injections. AB - The stability of ciprofloxacin in 5% dextrose and normal saline i.v. admixtures have been determined using a stability-indicating high performance liquid chromatographic assay method reported in the literature. The solutions were stored in plastic bags, a procedure being used in hospitals for in or out-patient therapy. The solutions were stable for at least 3 months when stored at room or refrigerator temperatures. They remained clear throughout the study and their pH values did not change. The expiry date recommended by the manufacturer appears to be very conservative from a chemical viewpoint. PMID- 7989407 TI - Stability of rifampin in two suspensions at room temperature. AB - The objective of our study was to determine the stability of rifampin (rifampcin) in two extemporaneously prepared suspensions at room temperature. Two suspensions were prepared in syrup by using intravenous rifampin (A) or rifampin capsules (B). Each suspension was stored in five plastic prescription bottles. During the first week, the mean measured concentrations of rifampin were nearly 100% of initial concentration in suspension A, but were 77-83% of the expected (labelled) concentration in suspension B. The maximum concentrations of rifampin were observed immediately after preparation of suspension A, but not until 14 days in suspension B. On day 56, the mean concentration of rifampin was about 95% of initial concentration in suspension A, and close to 90% of the labelled potency (10 mg/ml) in suspension B. Rifampin was found to be chemically stable in each suspension for 56 days at room temperature. Suspensions prepared from the capsules may be non-homogeneous and lead to unsatisfactory dosing. PMID- 7989408 TI - Correlation between nephrotoxicity and pharmacokinetic parameters of gentamicin. AB - Gentamicin pharmacokinetics were determined in 26 critically ill adult patients. All had normal or only moderately reduced renal function based on serum creatinine concentration and clearance. The average half-life of elimination was 4.68 h, creatinine clearance was 3.9 l/h, and gentamicin clearance was 2.86 l/h. There was a highly significant correlation between the area under the serum concentration-time curves (AUC) and the peak and trough concentrations (r = 0.908, 0.980, P < 0.05, respectively). Serum gentamicin concentrations rose rapidly in 10 patients who showed deterioration of kidney function after 5 days of therapy. Gentamicin peak concentrations increased by 31%, while trough concentration increased by 121%. The mean percentage change in half-life was 68.49%, while the mean percentage change in renal function was 44.38%. Linear regression analysis of AUC versus the percentage change in kidney function revealed a significant increase in AUC with decrease in kidney function (r = 0.909, P < 0.05). There was a significant increase in half-life with decrease in kidney function (r = 0.948, P < 0.05). PMID- 7989409 TI - [Effects of ischemia and revascularization on the epithelium of the small intestine: study on swine]. AB - Ischaemia of the small intestine leads to the destruction of the intestinal mucosa. The capacity of the epithelium to regenerate is proportional to the duration of revascularization. The aim of this work was to analyze the kinetic aspects of intestinal epithelial regeneration after destruction due to prolonged ischaemia. This study was conducted in 44 animals (swine) after development of an ischaemia-revascularization protocol of a jejunal loop and bipolar secondary cutaneous exteriorization. After a first series with ischaemia times of 1, 2, 3 and 4 hours, the 4 hour period of ischaemia was chosen for further analysis of the regeneration kinetics over a period of 21 days since it leads to regular and total destruction of the epithelium compatible with regeneration. This analysis included (1) a histological examination (semi-thin slices), (2) immunofluorescent detection of intestinal brush border proteins on frozen slices (villin, saccharase-isomaltase, aminopeptidase N, dipeptidylpeptidase-IV) and mucines, (3) measurement of specific intestinal hydrolase activities (saccharase, aminopeptidase N, dipeptidylpeptidase-IV and alkaline phosphatase) in enriched brush border fractions, and (4) an analysis of variations in intestinal flora. After the 4 hour ischaemia, total destruction of the epithelium with disappearance of the villin and intestinal hydrolases and disorganization of the mucosa invaded by mucosal lacks was observed. Epithelial regeneration was rapid and two days later the histological aspect of the mucosa showed apical expression (still discontinuous), villin and intestinal hydrolase activity. Luminal apical expression of the markers became continuous on day 4, demonstrating the total recovery of the intestinal barrier as confirmed by stable microbial flora. Mucine expression also returned to normal. This regeneration was however incomplete since the mucosa was seen to be flat, without villosities. Immunofluorescence showed the weak intensity of brush border activity and the very low specific activity of hydrolase. Values were below normal and did not start to rise again until day 21. If serum levels and associated brush border markers could be measured and were significant, they could be specific markers of regeneration in double stomy ischaemic-revascularized intestine and thus eliminate the need for early second look laparotomy. PMID- 7989410 TI - [Paraplegia and dissection of the abdominal aorta after closed trauma. Apropos of a case. Current review of the literature (1982-1993)]. AB - A case of dissection with thrombosis of the subrenal abdominal aorta after blunt trauma led to paraplegia and bilateral ischaemia of the lower limbs in addition to acute abdominal signs. A review of the recent literature (1982-1993) revealed 32 reported cases. The patients were predominantly male and most often victims of an automobile accident (18 cases) or crushing trauma (6 cases). The clinical picture associated diverse degrees of abdominal signs, ischaemia and sensorial motor impairment of the lower limbs. The diagnosis was established immediately on D0 in only 18 cases, early on days 1 to 7 in 4 cases and was late (day 8 to day 30) in 5 cases or very late (beyond day 30) in 6 cases. The difficulty in immediate diagnosis was related to the absent or incomplete vascular symptomatology or the late onset of the first signs. When a lesion of the aorta was suspected, an arteriography, angioscanner or peroperative exploration led to diagnosis. Neurological signs were frequent (10 cases including 8 with paraplegia) and generally related to ischaemia of the peripheral nerves. They may lead to denate from the diagnosis of vascular lesions. Fractures of the intima (17 cases) was the most frequent aortic lesion which also involved fracture of the media in a number of cases. Dissection was associated in 7 cases and complete or partial thrombosis of the aorta in 7. False aneurysms observed in 6 cases are the usual pathological form in cases of late diagnosis. Nearly all of the lesions were subrenal. Damage to abdominal organs was frequently observed.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7989411 TI - [Fistulas after Lewis-Santy's operations. Diagnosis, treatment, prevention]. AB - Fistulas of the anastomosis is the most severe complication after the Lewis-Santy operation. Over the last 10 years, we have performed 227 such operations for cancer of the oesophagus and have observed 16 fistulizations (7%). The aim of this study was to analyze the clinical manifestations and laboratory findings in these cases of fistulization as a function of the site of the plasty, the treatment and the results. We attempted to determine factors which could lead to means of preventing this complication. The fistula occurred at the oeso-gastric anastomosis in 11 cases (4.8%), at the apex of the gastric tube in 2 and on the line of gastric tubulization in 3. A comparison between patients with fistulas (group 1) and those without (group 2) showed that 19% of the patients in group 1 were over 70 years of age versus 9% in group 2 (NS). Three of the 16 patients (19%) with fistula had cirrhosis due to ethylism versus 2 of the 211 patients in group 2 (p < 0.001). Six patients among the 58 with palliative with a fistula (6%) (NS). Thoracic drainage was sufficient in 11 patients and surgical treatment was not required. In 5 reoperation (thoracotomy 4, cervicotomy 1) was necessary due to an intrapleural abscess. After 227 Lewis-Santy operations, 11 patients died during hospitalization (4.8%, 4 of which were complicated with fistula (1.7% of the operated patients and 25% of the patients with fistulas). The frequency of fistulizations after Lewis-Santy operation has decreasing (8%) and the gravity has improved (3 out of 4 were cured).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7989412 TI - [A rare complication of cholelithiasis. Ulceration of the cystic artery associated with cholecystoduodenal fistula]. AB - We observed a rare complication of gall stones revealed by a paroxysmal digestive haemorrhage. Ulceration of the cystic artery occurred due to a stone trapped in the neck associated with a cholecystoduodenal fistula. This is an exceptional cause of major digestive tract haemorrhage. Treatment is undertaken with that of the gall stone. Most often haemorrhages originating in the bile tract are occult. PMID- 7989413 TI - [Aneurysm of the hepatic artery treated by embolization]. AB - The hepatic artery aneurysm represent 16 to 20% of visceral artery aneurysms. The man of 40 years of age is often affected. This aneurysm is often asymptomatic. The rupture menace its evolution and justify the treatment. Echo-doppler-color constitute a non invasive exam of choice for diagnosis. Embolisation has a more extent indications. A case is reported of an aneurysm of the hepatic artery treated with embolisation with review of the literature. PMID- 7989414 TI - [Acute cholecystitis in the elderly]. AB - We retrospectively studied 150 patients aged over 65 years who had been operated for acute cholecystitis in order to define the surgical results and evaluate this treatment as a function of age. The patients were divided into two groups. Group I included patients between the age of 65 and 79 years, n = 99 (53 males and 46 females). Group II included patients aged 80 years and over, n = 51 (14 males and 37 females). The data were compared with the chi 2 test and the Kruskall and Wallis test. Associated affections were observed in 69 patients in group I and in 36 patients in group II (NS). The clinical picture was similar in the 2 groups with manifestations of pain in the right hypochondral region (group I, n = 97; group II, n = 50), fever (group I, n = 73; group 2, n = 38) and abdominal defence (group I, n = 62; group II, n = 35). Echography revealed the diagnosis in almost all cases in both groups. There was no statistical difference between the two groups in terms of mean operative delay and length of hospital stay. Age increased significantly the risk of exploration of the main bile duct (group I, n = 14; group II, n = 15, p < 0.05). Nevertheless, this exploration did not affect post-operative follow-up. Mortality was 6.7% with 4 deaths in group I and 6% in group II (NS). Post-operative complications were observed in 36 patients in group I and 28 in group II (p < 0.05) (43% overall including deaths).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7989416 TI - [Current problems of laparoscopic surgery]. PMID- 7989415 TI - [Experimental model of Barrett esophagus in dogs]. PMID- 7989417 TI - [Surgery in precarious situations. Mauritanian experience]. PMID- 7989419 TI - [Foreign bodies in the appendix and videoceliosurgery]. PMID- 7989420 TI - [Apropos of the assessment of "prophylaxis of deep vein thrombosis in orthopedic surgery"]. PMID- 7989421 TI - On recent advances in diabetes management. PMID- 7989418 TI - [Apropos of a voluminous hiatal hernia]. PMID- 7989422 TI - Case in point. Venous stars heralding carcinoma of the lung. PMID- 7989423 TI - Slow pulse, near-syncope, and congestive heart failure. PMID- 7989424 TI - Angioplasty in multivessel coronary artery disease. AB - Randomized trials directly comparing angioplasty with bypass surgery for complex multivessel disease are under way. Preliminary results suggest that angioplasty can be effective in some patient groups, so that neither procedure will predominate. The early results also suggest criteria to guide physicians in selecting the most appropriate method for individual patients. PMID- 7989425 TI - Sore throat: more than strep vs. non-strep. PMID- 7989426 TI - Deja vu from the trenches. PMID- 7989427 TI - Epigastric pain and weight loss in a middle-aged man. PMID- 7989428 TI - Spastic paraparesis of insidious onset. PMID- 7989429 TI - Cardiac transplantation: 2. Life with a new heart. AB - Most postoperative needs can be handled by the primary care physician. In particular, attention should be given to signs of allograft rejection, opportunistic infection, side effects from immunosuppressive agents, interactions between newly prescribed and established drugs, and immune-induced coronary artery disease. PMID- 7989430 TI - HCV-RNA detection in ultrasound-guided fine needle biopsies of liver nodules and surrounding tissue. AB - HCV-RNA was examined in serum and liver tissue obtained from 8 hepatitis B surface antigen (HBsAg) negative patients with liver nodules ranging in size from 2 to 11 cm. Histological examination of ultrasound-guided fine needle biopsies revealed the presence of hepatocellular carcinoma (HCC) in six patients (5 of whom were anti-HCV positive), cholangiocarcinoma in 1 patient (anti-HCV positive) and dysplastic regenerative nodule in 1 patient (anti-HCV negative). The HCCs were surrounded by cirrhosis (3 cases), chronic active hepatitis (CAH) (n = 2) and post hepatitic fibrosis (n = 1), the cholangiocarcinoma by CAH and the regenerative nodule by cirrhotic liver. Total and replicative intermediate HCV RNA was analyzed by reverse-transcription-nested PCR of the 5'-untranslated region. The five patients with HCC had HCV-RNA in serum, in tumorous and surrounding liver tissues. The viral nucleic acid was also detected in the cirrhotic tissue surrounding the cholangiocarcinoma but not in the tumor. Two out of 5 HCC patients had replicative intermediate RNA (negative strand) in tumorous tissue, 4 in nontumorous tissue and 3 in serum. These results demonstrate that fine needle biopsy can provide sufficient material for both histological examination and HCV-RNA determination and suggest the existence of continuous viral replication during the carcinogenic process. PMID- 7989431 TI - Identification of GPCMV infected cells in vitro and in vivo with a monoclonal antibody. AB - A monoclonal antibody was made which identifies a 160-180 kDa structural protein in guinea pig cytomegalovirus (GPCMV) infected cells by Western blot using non reducing conditions. This protein was shown to be a virion structural protein by purification of GPCMV on a density viscosity gradient and Western blot analysis. Phosphoanacetic acid (PAA) experiments suggest that the protein is a late GPCMV protein. In vitro the monoclonal antibody labels a cytoplasmic protein in infected guinea pig embryo fibroblasts by 12 h postinfection. The monoclonal antibody also identifies GPCMV infected cells in vivo in paraffin embedded formalin fixed tissue. PMID- 7989432 TI - Mirror image in vivo electroblotting technique, a new technique for visualizing virus particles electrophoretically transferred from infected leaves to nitrocellulose membranes. AB - A new technique was developed for visualizing virus particles electrophoretically transferred from infected leaves to nitrocellulose membranes. This technique was used to study the distribution of peanut mottle virus (PMV) particles in vivo. The immobilized transferable virus proteins from leaf tissue to nitrocellulose membranes were detected by an enzyme-linked immunobinding technique. The free binding groups on the nitrocellulose membrane were blocked with casein. The nitrocellulose membrane was then treated with PMV-specific antiserum. The virus bound antibodies were located by protein A-peroxidase or protein A-alkaline phosphatase conjugate followed by the peroxidase substrate mixture, 4-chloro-1 naphthol and H2O2, in the first case or the alkaline phosphatase substrate mixture, 5-bromo-4-chloro-3-indolyl phosphate and Nitroblue tetrazolium in the second case. The locations of virus particles were detected by the corresponding reaction product. A mirror image was obtained on nitrocellulose membrane showing a pattern identical to that of necrotic lesions on leaf pieces but with a significantly larger size of local lesion copy, indicating the presence of virus particles in the apparently healthy tissue outside the necrotic lesion. The new technique is expected, because of its relative simplicity and sensitivity, to be useful for many other fields of biological research where the in vivo distribution of pathogens, antigenic molecules including drugs, or cells of specific antigenic molecules such as cancer or genetically engineered cells needs to be investigated. PMID- 7989433 TI - Detection of enterovirus RNA in clinical samples by nested polymerase chain reaction for rapid diagnosis of enterovirus infection. AB - Employing a nested polymerase chain reaction with primers from the 5' non translated region of the enterovirus genome, we detected enteroviral RNA from patients with a variety of enterovirus-associated clinical syndromes. This technique was found to be sensitive (detecting enteroviral RNA extracted from 0.1 50% tissue culture infectious dose) and specific; no specific PCR product was detected from RNA extracts of a variety of non-enterovirus isolates. Although the technique is of comparable sensitivity to single round polymerase chain reaction followed by Southern blot hybridization, it was more rapid, since it enabled a diagnosis to be made within 1 day. Thus, using nested polymerase chain reaction we were able to detect enteroviral RNA in 31 of 46 clinical specimens from 17 of 23 patients with suspected enterovirus infections. The samples included cerebrospinal fluid, throat swabs, stool, vesicle fluid, peripheral blood lymphocytes, whole blood and pericardial effusion. In contrast virus was isolated in only 17 of 42 clinical specimens from 12 of 22 these patients. In preliminary studies, restriction endonuclease analysis of polymerase chain reaction products enabled us to distinguish between non-polio enteroviruses and poliovirus types 1, 2, and 3. This additional technique may be useful in distinguishing between such infections in polio-endemic countries where rapid public health measures may be required. PMID- 7989434 TI - Construction of gag, pol, and env specific riboprobes for confirmation of HIV-1 specific polymerase chain reaction products. AB - Conserved regions of the gag, pol, and env genes of HIV-1 pBH10 DNA (gag nucleotides(nt)1520-1665, pol nt 2326-2663, env nt 7192-7333; Ratner et al., 1985) were amplified by the polymerase chain reaction (PCR) using oligonucleotides complementary to the termini of these regions as primers. Primer areas of the amplified DNA were then removed by digestion with restriction endonucleases, and the internal fragments purified and cloned in both orientations into the 'riboprobe' transcription vector pGEM-5Z. Riboprobes made from these plasmids did detect the specific sequences of pBH10 DNA and of HIV-1 DNA amplified by PCR from clinical material. The riboprobes will be useful to confirm the specificity of PCR-amplified fragments of lymphocyte DNA obtained from infants of HIV-infected mothers and from high risk, but seronegative contacts of HIV-1-infected individuals. PMID- 7989435 TI - Identification of Norwalk virus in artificially seeded shellfish and selected foods. AB - A rotavirus dsRNA purification protocol was adapted to extract Norwalk ssRNA from artificially contaminated shellfish, and a sensitive reverse transcription polymerase chain reaction assay for Norwalk virus was devised to identify an estimated 20-200 genomic copies. The technique includes deproteinization with guanidinium isothiocyanate, adsorption of RNA to hydroxyapatite, and sequential precipitation with cetyltrimethylammonium bromide and ethanol. The protocol allows high recovery of viral RNA free of enzymatic inhibitors from oysters, clams, and a variety of food matrices. Norwalk virus sequences were copied and amplified by using primers selected from the polymerase gene. Digestion of the amplified products with restriction enzymes ensured the specificity of the test. This rapid and sensitive assay may significantly improve the prospect for the routine screening of the uncultivatable Norwalk virus in food stuffs. PMID- 7989436 TI - Rapid small-scale isolation of herpes simplex virus DNA. AB - A method has been developed for the rapid isolation of herpes simplex virus DNA analogous to miniprep methods for bacterial plasmid isolation. Infected Vero cells are lysed with three freeze-thaw cycles, and the nuclei are removed by centrifugation. DNA is released from the virions in the supernatant by proteinase K digestion. Then the DNA is extracted with phenol/chloroform and precipitated with ethanol. This method requires only small amounts of infected cells as a source of viral DNA, does not use radioactivity, and routinely produces DNA of sufficient purity to be used for restriction fragment length polymorphism (RFLP) analysis on ethidium-stained gels. PMID- 7989437 TI - Sensitive detection of morbillivirus cell-free transcription in a direct RNase protection assay. AB - Cell-free measurement of viral transcription is necessary to determine if alterations of in situ levels of viral mRNA represent altered mRNA production or stability. Conditions for cell-free genomic transcription have been developed for the morbilliviruses canine distemper virus (CDV) and measles virus (MV), although the means for detecting nascent transcripts in these assays are insensitive in some cell systems. This work describes a technique in which CDV cell-free transcription reactions are modified so that non-radiolabeled transcripts are produced, precluding the need for limiting nucleotide concentrations in the reaction mixtures and allowing nucleotide concentrations which support optimal polymerase activities. Cell-free transcripts are then detected using anti-sense gene-specific riboprobes in an RNase protection assay (RPA). This approach is more sensitive than conventional slot blot analyses in detecting radiolabeled nascent transcripts and is efficacious in cell systems supporting inherently low levels of virus gene expression. Preformed viral RNA is distinguished from RNA synthesized during the course of the cell-free reactions by using a direct RPA (i.e., hybridization of target RNA prior to phenol/chloroform extraction). The use of this approach will expand the range of virus-host systems in which determinants of morbillivirus transcription can be characterized. PMID- 7989438 TI - Survey of cell lines in the American Type Culture Collection for bovine viral diarrhea virus. AB - Cell lines originating from cattle, sheep, goat, deer, bison, swine, rabbit, hamster, cat, dog, monkey, human, and mosquito were obtained from the American Type Culture Collection and tested for contamination with bovine viral diarrhea virus (BVDV). Immunocytochemical procedures and polymerase chain reaction (PCR) amplification were used to detect viral antigen or viral RNA in 13 of 41 cell lines. The results of these procedures correlated exactly. Cell lines derived from cattle, sheep, goat, deer, bison, rabbit, and domestic cat were found contaminated with BVDV. Attempts were made to experimentally infect 14 swine, rabbit, hamster, cat, dog, monkey, and human cell lines that had been found free of virus. All swine cell lines, and most rabbit and cat cell lines, became infected with BVDV. Hamster, human, dog, and certain rabbit and cat cells were refractory to BVDV infection. Experimental infection of monkey cells produced variable results. PMID- 7989440 TI - A PCR-restriction enzyme technique for determining dengue virus subgroups within serotypes. AB - The polymerase chain reaction (PCR) and restriction enzyme analysis were used to develop a rapid and simple procedure for identifying geographic subgroups of dengue virus within serotypes for epidemiologic investigations. The entire structural protein region of dengue viruses was amplified and the products were digested with the endonucleases AluI or DdeI. By comparing the restriction fragment length polymorphisms (RFLPs), we recognized dengue-2 and dengue-3 subgroups that corresponded to those previously determined by oligonucleotide fingerprinting or genomic sequencing. This procedure can be performed in 2 days without the use of radioisotopes, and results can be interpreted without computer analysis. For those analyses which require only subgroup affiliations, this is a useful tool for rapidly screening multiple virus isolates. PMID- 7989439 TI - Polymerase chain reaction kinetics when using a positive internal control target to quantitatively detect cytomegalovirus target sequences. AB - High-performance liquid chromatography (HPLC) was used to detect and quantify cytomegalovirus (CMV) specific polymerase chain reaction (PCR) products generated during PCR co-amplification. PCR of CMV AD 169 or a plasmid which contains the CMV AD 169 native target sequence using the CMV primer set of Hsia et al. (J. Clin. Microbiol. 27, 1802-1809) generates a 152 bp PCR product. A CMV control sequence plasmid which shared the primer sequence of native CMV AD 169 but when amplified produces a larger 362 bp product was constructed. Under co amplification conditions there was a linear relationship (over 3 logs) between the molar ratio of input CMV native and control target sequence and the molar ratio of the output PCR products as detected by HPLC despite differences between the two PCR target and product sizes. Co-amplifying known amounts of CMV control sequence plasmid as an internal standard allowed accurate quantitation of the amount of CMV native target sequence in a sample when the two PCR targets were present in approximately equimolar amounts +/- 1.5 log (coefficient of variation (CV) < 12%). By modifying the amount of CMV control target sequence plasmid used for co-amplification, accurate detection of the amount of CMV native sequence in samples could be extended to 5 logs, standard error (S.E.) < or = 16%. Precise quantitation of PCR targets using co-amplification PCR requires multiple sample dilutions to ensure that the CMV native target sequence was in a close equimolar relationship with the CMV control sequence at the time of PCR amplification. PMID- 7989441 TI - Baculovirus expression of non-structural protein NS2 and core protein VP7 of African horsesickness virus serotype 3 and their use as antigens in an indirect ELISA. AB - Non-structural protein NS2 and core protein VP7 of African horsesickness virus serotype 3 (AHSV3) were expressed in Spodoptera frugiperda cells by recombinant baculoviruses containing the relevant genes. These proteins were purified and analysed by polyacrylamide gel electrophoresis and Western blot. NS2 and VP7 were used separately as antigens in an indirect ELISA for the detection of AHSV antibodies. Both antigens cross-reacted with hyperimmune guinea-pig antisera to infected cell lysates of all nine known AHSV serotypes and to antisera obtained from horses immunized with attenuated virus of seven AHSV serotypes. PMID- 7989442 TI - MTT colorimetric assay system for the screening of anti-orthomyxo- and anti paramyxoviral agents. AB - A rapid and sensitive method was developed for screening potential antiviral agents against orthomyxo- and paramyxoviruses, using the MTT method with cell culture suspensions. The cell lines used for the assay were as follows: MDCK cells for the influenza A virus (Fluv. A), HeLa cells for the respiratory syncytial virus (RSV), and Vero cells for the measles virus (MSV). Test compounds were diluted and plated in 96-well round-bottomed microtiter plates. Trypsinized cell suspensions and viruses were added to each well, the plates were then centrifuged (700 x g, 5 min, room temperature), and incubated for several days. The MTT assay was carried out after the degeneration of virus-infected cells became evident. The optical density (OD) of formazan was determined using a computer-controlled microplate reader. With this assay system, the EC50 values of Ribavirin (used as the reference compound) were 3.7 micrograms/ml for Fluv. A, 4.5 micrograms/ml for RSV, and 12.3 micrograms/ml for MSV, respectively. These EC50 values were equivalent to those obtained using the plaque reduction assay. The confluent cell culture system was inadequate for antiviral assays against RSV and MSV when the MTT method was used, because the inhibition of formazan formation was not observed in viral-infected cells. Moreover, the suspension method is more sensitive to the cytotoxicity of antiviral agents than the confluent cell culture system. PMID- 7989444 TI - Detection of genetic variations in serotype I isolates of infectious bursal disease virus using polymerase chain reaction and restriction endonuclease analysis. AB - Reverse transcription with polymerase chain reaction (PCR) followed by restriction endonuclease analysis detected genetic variations among serotype I isolates of infectious bursal disease virus (IBDV). Using a set of synthetic primers derived from the large genome segment of APHIS-IBDV, the hypervariable region (AccI-SpeI fragment) located in the VP2 gene was amplified. With all strains, a cDNA fragment of approximately 643 bp was amplified, indicating that there were no apparent deletions or insertions in this region among isolates. Fragments amplified from 9 isolates were digested with 14 restriction enzymes. Restriction fragment profiles generated by restriction enzymes NaeI, StuI, TaqI, and SacI, showed genetic variations among isolates. This study provided a simple and sensitive method for detection of genetic variations among isolates that are closely related serologically and could not be differentiated using current serologic methods. PMID- 7989443 TI - The duration of fixation influences the yield of HCV cDNA-PCR products from formalin-fixed, paraffin-embedded liver tissue. AB - The extent of hepatitis C virus (HCV) RNA loss during increasing periods of fixation of liver tissue in formalin was examined. For this purpose human liver tissue, known to be HCV RNA positive and stored at -70 degrees C until use, was cut into small slices (n = 9), which were fixed in phosphate-buffered formalin for increasing periods of time before embedding in paraffin. Nucleic acids were extracted from each slice of formalin-fixed, paraffin-embedded liver tissue and HCV RNA loss during fixation was semi-quantified by testing 10-fold dilutions of each extract in an HCV cDNA-PCR assay. The endpoint dilution for HCV RNA detection by cDNA-PCR in liver slices fixed in buffered formalin for 8-24 h was comparable to the endpoint dilutions found for 'fresh', non-fixed liver slices. After fixation for 2-3 days the endpoint dilution for HCV RNA detection was 10(2) to 10(3)-fold less. After 2-4 weeks of formalin-fixation, HCV RNA was detectable from undiluted nucleic acid extracts only. It is concluded that formalin-fixed, paraffin-embedded liver biopsies can be used for HCV RNA detection by cDNA-PCR, on condition that the liver tissue has been embedded in paraffin within 24 h of formalin-fixation. PMID- 7989445 TI - Anti-idiotypic antibodies generated by sequential immunization detect the shared idiotype on antibodies to pseudorabies virus antigens. AB - Anti-idiotypic antibodies (anti-Id or Ab2) were generated in Balb/c mice against either mouse monoclonal or swine polyclonal antibodies (Ab1) to pseudorabies virus (PRV) antigens by conventional and sequential immunization methods. In the conventional method, one antibody preparation was repeatedly injected into the animals, whereas three anti-PRV antibody preparations were used alternately for the sequential immunization procedure. Anti-Ids were serologically characterized for possession of the Ab2s that detect shared idiotype (IdX) on antibodies to PRV antigens. Only the Ab2s that were generated by the sequential immunization method recognized the IdX present on murine and swine antibodies to PRV. The sequential immunization method described herein was anticipated to be helpful for generating virus specific Ab2s as candidates for serodiagnostic reagents or vaccines. PMID- 7989446 TI - Rapid detection of rotavirus in faeces using a dipstick system with monoclonal antibodies and colloidal gold as marker. AB - Rotavirus (RV) is known to be the most common cause of severe diarrhoea in infants and young children, each year leading to an estimated 800,000-900,000 deaths. RV also infects bovines and other species, with high morbidity and mortality. A rapid and simple 'naked-eye' dipstick system was developed to detect human RV in faeces, using nitrocellulose as solid phase, two monoclonal antibodies, and colloidal gold as marker. The system detects 10(4) viral particles (1-2 ng)/g of faeces. For human RV the specificity and sensitivity were 100% when compared with a commercial latex system, and 99% and 98%, respectively, when correlated with traditional RNA-PAGE, and 100% and 98% compared to an ELISA system. PMID- 7989447 TI - Development of a novel quantitative assay for the measurement of chloramphenicol acetyl transferase (CAT) mRNA. AB - Most host cells transfected with chloramphenicol acetyl transferase (CAT) expressing plasmids display relatively low levels of constitutive CAT activity. While this is ideal to study factors that enhance gene transcription, decreases in CAT levels are difficult to quantitate, using conventional CAT assays. Thus, investigators have used cell activating agents or co-transfection of the cell lines with a second enhancer plasmid to yield higher levels of CAT activity. However, such measures can interfere with the cellular pathways studied and eventually alter the results. To avoid this problem, our laboratory has designed an RT-PCR assay to quantitate CAT mRNA. The ability of this assay to detect CAT mRNA but not CAT DNA demonstrates its specificity and is achieved using a tailed oligoprimer for the reverse transcription step. This assay is able to measure the equivalent of as few as eight copies of CAT mRNA, is reproducible and relatively easy to perform. The quantitative capability of the assay relies on a constant production of CAT mRNA, which is achieved using permanently transfected and cloned cell lines bearing a defined number of CAT DNA copies per cell. This assay provides a tool for monitoring events at the transcriptional level and thereby complements the currently used CAT ELISA and thin-layer chromatography assays. PMID- 7989448 TI - HCV RNA detection in heparinized blood by direct genomic RNA capture onto paramagnetic particles. PMID- 7989449 TI - Comparison of the labeled avidin-biotin and the conventional enzyme-linked immunosorbent assay for detecting antibody to reovirus in chickens. AB - A labeled avidin-biotin enzyme-linked immunosorbent assay (LAB-ELISA) for detecting antibodies to avian reovirus (ARV) in chicken sera was developed and compared with conventional ELISA. Purified ARV, biotin-labeled rabbit anti chicken IgG conjugate, and horseradish peroxidase-labeled avidin were used in the LAB-ELISA. The two types of ELISA had the similar ability to clearly distinguish ARV-positive and -negative sera. Furthermore, non-specific reactions with the two ELISAs against sera from ARV-negative chickens were reduced markedly. When sera from farm chickens were tested by the two ELISAs and serum neutralization (SN), the correlation rates between SN and conventional ELISA, and SN and LAB-ELISA were similar and were 93.4% and 92.3%, respectively. PMID- 7989450 TI - Clinical review 64: Pathophysiology and natural history of male infertility. PMID- 7989451 TI - A-I-D-S: the new endocrine epidemic. PMID- 7989452 TI - Endocrine evaluation of incidentally discovered adrenal masses (incidentalomas) AB - Since 1989, 45 patients [pts; 26 females and 19 males, aged 19-79 yr (median, 58)] bearing incidentally discovered adrenal masses were studied. The aim of the study was to verify the prevalence of hormone activity in clinically silent adrenal masses. Endocrine work-up included determination of urinary catecholamines and their metabolites, measurement of PRA and aldosterone levels in clino- and orthostatic posture, and basal and dynamic [dexamethasone (dex) suppression and ovine CRH stimulation] evaluation of hypothalamic-pituitary adrenal axis. The most frequent finding was the reduction of dehydroepiandrosterone sulfate (DHEA-S) levels below the third percentile of controls in 19 (42%) pts. DHEA-S levels were significantly lower in pts than in controls [68 (range, 5-1000) vs. 208 (34-326) micrograms/dL; 1.8 (0.1-27.1) vs. 5.6 (0.9-8.8) mumol/L; P < 0.001]. Three pts (7%) had high 24-h mean serum cortisol levels, and 6 (14%) had blunted day-night amplitude of cortisol rhythm. Defective dex suppressibility was found in 15% of pts vs. 8% of controls (P < 0.05). ACTH and cortisol responses to ovine CRH did not significantly differ between pts and controls, although blunted ACTH responses were found in 22% of the cases. The above-mentioned endocrine alterations could be accounted for by autonomous cortisol secretion by the adrenal nodule at a rate not sufficient to give clinical expression, but able to inhibit to some extent the hypothalamic pituitary-adrenal axis. These results indicate that silent cortisol hypersecretion is frequently observed in pts with adrenal incidentaloma even if progression to overt Cushing's syndrome seems unlikely. Indeed, the size of the mass and the hormone pattern remained substantially unchanged in 9 pts followed up for 12 months. From merely a cost/benefit ratio, the evaluation of DHEA-S levels and dex suppression has sufficient sensitivity to identify the occurrence of silent hypercortisolism. PMID- 7989453 TI - Primary adrenal insufficiency in patients with the acquired immunodeficiency syndrome: a report of five cases. PMID- 7989454 TI - Circulating fibroblast growth factor-like autoantibodies in two patients with multiple endocrine neoplasia type 1 and prolactinoma. AB - Basic fibroblast growth factor (bFGF) is a potent endothelial cell mitogen found in a variety of normal and tumor tissues. bFGF lacks a classical amino-terminal signal sequence and is not readily detectable in plasma from normal subjects. In earlier studies we showed increased bFGF-like mitogenic activity for parathyroid derived endothelial cells and (increased) bFGF immunoreactivity (0.24-1.28 ng/mL) in plasma of subjects with multiple endocrine neoplasia type 1 (MEN-1). In the present study we examined the proliferative activity of MEN-1 and normal plasmas (applied to protein-A columns) in calf pulmonary artery endothelial cells. Protein-A-eluted activity in plasma from MEN-1 prolactinoma plasma exceeded activity from normal and MEN-1 nonprolactinoma plasma in three of eight MEN-1 subjects with untreated or recurrent prolactinoma. Protein-A-eluted active fractions from MEN-1 prolactinoma plasma had several properties of an immunoglobulin G, including affinity for antihuman immunoglobulin G (IgG) agarose, sensitivity to thiols, and (prepared by sodium dodecyl sulfate polyacrylamide gel electrophoresis under reducing conditions) apparent mol wt corresponding to those of the heavy and light chains of IgG. The IgG fraction of MEN-1 prolactinoma plasma had far more activity in endothelial cells than did optimal concentrations of known growth factors or conditioned medium from prolactinoma cells. Endothelial cell bioactivity in protein-A-eluted fractions from MEN-1 prolactinoma plasma was neutralized 70% by rabbit antibodies to intact bFGF. These results imply novel growth stimulatory bFGF-like autoantibodies in a subset of MEN-1 patients with prolactinoma. PMID- 7989455 TI - Effects of metformin treatment on whole-body and splanchnic amino acid turnover in mild type 2 diabetes. AB - The effects of metformin therapy on whole body and splanchnic amino acid turnover are not known. Therefore, we have studied fasting and postprandial phenylalanine kinetics in type 2 diabetic subjects (non-insulin-dependent diabetes mellitus), previously treated with diet only, both before and after 4 weeks of either metformin (850 mg twice a day) (n = 11) or placebo administration (n = 6). Phenylalanine kinetic was evaluated by means of a multiple isotope technique: tritiated phenylalanine was infused i.v., whereas carbon-labeled phenylalanine was incorporated into a chemically-defined meal. Compared with placebo, metformin administration decreased both fasting (from 162 +/- 17 to 141 +/- 20 mg/dl) and postprandial (from 217 +/- 20 to 164 +/- 20 mg/dl) glucose concentrations (P < 0.05-P < 0.01). Fasting insulin concentrations were unaffected, but postmeal insulin tended to be lower (P < 0.06) after metformin. Compared with the pretreatment period, metformin administration did not change total phenylalanine rate of appearance (fasted state, 0.74 +/- 0.10 vs. 0.71 +/- 0.08 mumol/kg.min; fed state, 0.77 +/- 0.10 vs. 0.75 +/- 0.08 mumol/kg.min, respectively), dietary and endogenous phenylalanine rate of appearance, dietary phenylalanine oxidation, and splanchnic uptake, similar to what was observed in the placebo group. Our data indicate that, at least after a 4-week treatment, metformin does not affect fasting and postprandial protein turnover, as indicated by phenylalanine data, in subjects with mild non-insulin-dependent diabetes mellitus. PMID- 7989456 TI - Insulin secretion, insulin action and non-insulin-dependent glucose uptake in pancreas transplant recipients. AB - To assess individual factors responsible of overall glucose tolerance after successful pancreas transplantation, an i.v. glucose tolerance test, with frequent blood sampling and tolbutamide administration to elicit a second insulin response was used to estimate insulin sensitivity (SI) and glucose effectiveness (SG) with Bergman's minimal model. Insulin secretion was calculated from the combined insulin-C-peptide kinetics method. These parameters were quantified in identically immunosupressed transplants: ISPx, four segmental pancreas recipients with impaired glucose tolerance; TSPx, five segmental pancrease recipients with normal glucose tolerance; WPx, five whole pancreas recipients with normal glucose tolerance; and in two controls groups, Kx, eight nondiabetic kidney recipients, and Ns, eight normal subjects. All participants had normal fasting plasma glucose and normal glycosylated hemoglobin A1C levels. The glucose tolerance KG value was significantly reduced only in ISPx compared with Ns (P < 0.05). SI was reduced by 60% in ISPx, WPx, and Kx compared with normal subjects (P < 0.05), whereas SI was reduced by 30% in TSPx compared with normal controls (P = NS). The reduction in SG was the same in all pancreas transplanted groups, as compared to Kx and Ns (by 33% and 40%, respectively, P < 0.05). The first-phase insulin secretion (0-5 min) was markedly reduced in ISPx and TSPx compared with Ns (by 76% and 50%), to Kx (by 84% and 66%) and to WPx (by 73% and 45%), respectively (P < 0.05), but similar to Ns in WPx. The overall incremental insulin secretion was reduced in ISPx compared with Ns, WPx, and Kx (by 38%, 62%, and 73%, respectively, P < 0.05) and reduced in TSPx compared to WPx and Kx (by 47% and 67%, respectively, P < 0.05) Ns secreted 43% of the total amount of insulin during the first phase the corresponding value was only 13% in ISPx vs. 24% in TSPx, 24% in Kx, and 25% in WPx, respectively (P < 0.05). In conclusion, after pancreas transplantation, the overall glucose tolerance is determined by the net effect of reductions in insulin sensitivity and glucose effectiveness and in the adaptability of the beta cells to ensure sufficient insulin secretion. beta-cell function was impaired in both the whole pancreas and segmental transplant recipients, and the failure to increase insulin secretion sufficiently leads to glucose intolerance. PMID- 7989457 TI - Disproportionately elevated proinsulin levels precede the onset of insulin dependent diabetes mellitus in siblings with low first phase insulin responses. The Childhood Diabetes in Finland Study Group. AB - The objective of this study was to test whether levels of proinsulin immunoreactivity (PIM) relative to those of insulin immunoreactivity (IRI) or C peptide are changed and related to subclinical beta-cell dysfunction in siblings of insulin-dependent diabetes mellitus (IDDM) patients. Twenty-three siblings, previously found positive for islet cell antibodies and/or insulin autoantibodies, were divided into 2 groups according to their first phase insulin response (FPIR) to i.v. glucose tolerance tests (IVGTTs) sequentially performed during an observation period of 2 yr. Eleven siblings had diminished FPIR on at least 1 occasion (group 1), whereas 12 siblings had a normal FPIR on all occasions studied (group 2). All underwent a further IVGTT (0.5 g glucose/kg BW), and serum samples were taken at 0, 1, 3, 6, 10, 20, 30, 40, 50, and 60 min. The 2 groups had comparable median age, female/male ratio, weight, height, fasting blood glucose, immunoreactive insulin, C-peptide, and insulin autoantibodies levels, but group 1 had significantly higher islet cell antibodies levels. Fasting median PIM/IRI and PIM/C-peptide ratios were 2- to 3-fold higher in group 1 [10.5% (range, 1.8-93.8%) vs. 5.2% (range, 1.9-14.3%) and 3.3% (range, 0.4 23.1%) vs. 1.3% (range, 0.7-2.6%; P < 0.05]. Fasting PIM/C-peptide ratios correlated inversely with FPIRs (rs = -0.68; P < 0.01). During glucose stimulation, maximal responses of IRI and C-peptide were 4-fold lower in group 1, and the time of maximal responses of IRI and C-peptide occurred later in group 1 than in group 2. In contrast, no difference in maximal responses of PIM was found, but the time of maximal responses of PIM occurred later in group 1. Nine of 11 siblings in group 1 presented with IDDM 1-28 months after the test, compared to none in group 2. In group 1 a paradoxical inhibitory response of PIM was observed during the first 6 min of the IVGTT. These data indicate that fasting PIM/IRI and/or PIM/C-peptide ratio reflects subclinical beta-cell dysfunction in prediabetic subjects with evidence of immunological beta-cell assault and suggests that an elevated ratio may be an additional marker for later development of IDDM. PMID- 7989458 TI - Immunoreactive proinsulin-like growth factor-II levels in healthy subjects, patients with growth hormone deficiency, and patients with type 1 diabetes: effects of insulin-like growth factor-I and insulin. AB - Proinsulin-like growth factor-II (IGF-IIE), with an E-peptide elongation at the C terminal, is found in the circulation and in different body fluids with mol wt between 10-16 kilodaltons compared to native 7.4-kilodalton IGF-II. Some tumors overexpress IGF-II and IGF-IIE with increased levels in patients serum, sometimes causing hypoglycemia (nonislet cell tumor-induced hypoglycemia). We have developed a RIA for a 15-amino acid part of the E-peptide. By using the E16 peptide as the labeled ligand, this RIA is unaffected by the presence of IGF binding protein in the samples. Gel chromatography under acid and neutral conditions revealed that all IGF-IIE was detected without prior separation of serum. Using recombinant IGF-IIE21 as standard, we determined normal levels in 70 males and 67 females between 20-70 yr of age. The average was 46.6 +/- 1.1 micrograms/L, and the 95% confidence interval was between 21.4-71.9 micrograms/L. A significantly higher level was found in males (49.0 +/- 1.6 micrograms/L) compared to females (44.2 +/- 1.3 micrograms/L). In two nonislet cell tumor induced hypoglycemia patients, levels of immunoreactive (ir) IGF-IIE were 2.5-3 times normal levels. GH-deficient patients had normal levels, but daily sc injections of recombinant human IGF-I decreased serum irIGF-IIE by 40%. Insulin dependent diabetic patients undergoing liver venous catheterization had normal basal levels of irIGF-IIE in peripheral blood. A 180-min insulin infusion decreased the levels significantly in the vena hepatica, but no splanchnic gradient was observed. PMID- 7989459 TI - Direct regulation of human myometrial contractions by human chorionic gonadotropin. AB - Our laboratory previously demonstrated that the human myometrium contains functional hCG/LH receptors. The present study investigated whether hCG can directly regulate oxytocin-stimulated human myometrial contractions. Uterine specimens were obtained from 30- to 40-yr-old women undergoing hysterectomy for leiomyomata, metrorrhagia, or prolapse. Myometrial strips from the lower uterine segment were primed for 24 h with 2.2 nmol/L estradiol. Then, the slices were incubated for 4 h at 37 C with or without 10 nmol/L hCG and stimulated with 1 mumol/L oxytocin, and the contractions were measured. The results showed that hCG inhibited the amplitude while paradoxically increasing the frequency of contractions. The effect of hCG was seen in proliferative, but not secretory, phase myometrial specimens. hCG had no effect on rat hepatic portal vein smooth muscle contractions, suggesting that the hCG action was tissue specific. Oxytocin treatment of human myometrial smooth muscle cells resulted in a dose-dependent increase in intracellular free Ca2+ levels. Pretreatment with hCG resulted in an attenuation of the oxytocin response, suggesting that the action of hCG was mediated by decreasing intracellular free Ca2+ levels. In summary, our results demonstrate that hCG can directly inhibit the amplitude of oxytocin-stimulated contractions of human myometria from the proliferative phase of the cycle. The hCG action is tissue specific and appears to be mediated by decreasing intracellular free Ca2+ levels in myometrial smooth muscle cells. PMID- 7989460 TI - Acute administration of a 3 beta-hydroxysteroid dehydrogenase inhibitor to rhesus monkeys at the midluteal phase of the menstrual cycle: evidence for possible autocrine regulation of the primate corpus luteum by progesterone. AB - Colocalization of progesterone receptors and 3 beta-hydroxysteroid dehydrogenase (3 beta HSD), a key enzyme in progesterone biosynthesis, in macaque luteal cells suggest that progesterone has an autocrine role in the regulation of primate luteal function. To test this hypothesis, we administered trilostane, a 3 beta HSD inhibitor, to rhesus macaques at the midluteal phase of spontaneous menstrual cycles to rapidly and reversibly reduce progesterone production. Animals received trilostane (600 mg/dose; treated group; n = 5) or vehicle (control group; n = 4) orally on days 6-7 of the luteal phase. Trilostane significantly (P < 0.05) elevated pregnenolone levels within 1 h of treatment compared to those in vehicle treated animals; after 1 day of treatment, the mean pregnenolone level (173 nmol/L) was 86-fold greater than the control value. Pregnenolone levels dropped after cessation of drug administration and became indistinguishable from control levels by day 13. Trilostane significantly reduced serum progesterone levels within 3 h of initial administration (P < 0.01), and levels remained near baseline (1.0 nmol/L) throughout the 2 days of treatment. Progesterone levels also remained low after cessation of trilostane treatment in four of five monkeys, and trilostane-treated animals experienced a shorter luteal phase than vehicle-treated animals (7.8 +/- 0.2 vs. 16 +/- 1 days; P < 0.01). Histological analysis (n = 3/group) revealed indexes of premature structural luteolysis by 4 days after the onset of trilostane administration. Exposure to trilostane had no effect on the percentage of luteal cells expressing progesterone receptors, as determined by immunocytochemistry. Serum LH levels were not different between treatment and control groups throughout the experimental period. As trilostane dramatically reduced serum progesterone and induced premature menses without major concurrent alteration in serum cortisol, we conclude that trilostane ios an effective, rapidly acting inhibitor of 3 beta HSD in the macaque corpus luteum during the midluteal phase of the menstrual cycle. Progesterone production did not typically resume after cessation of trilostane treatment despite continuing gonadotropin support luteolysis. Thus, progesterone or a related metabolite may be required to maintain the function and structural integrity of the primate corpus luteum during the normal menstrual cycle. PMID- 7989461 TI - Continuous therapy with pamidronate, a potent bisphosphonate, in postmenopausal osteoporosis. AB - There is a need for effective and acceptable therapies for postmenopausal osteoporosis. The bisphosphonates show promise in this role, but the effects of the potent bisphosphonates in established osteoporosis have not yet been reported. We performed a 2-yr, randomized, double blind, placebo-controlled trial of pamidronate (150 mg/day) in 48 postmenopausal osteoporotic women. Bone mineral density of the total body, lumbar spine, and proximal femur was measured every 6 months by dual energy x-ray absorptiometry. Bone mineral density increased progressively in the total body (1.9 +/- 0.7%; P < 0.01), lumbar spine (7.0 +/- 1.0%; P < 0.0001), and femoral trochanter (5.4 +/- 1.3%; P < 0.001) in subjects receiving pamidronate, but did not change significantly in those receiving placebo. There were significant decreases in bone density at both the femoral neck (P < 0.02) and Ward's triangle (P < 0.01) in subjects taking placebo, which did not occur in the pamidronate group. The differences between the treatment groups were significant at all sites (0.0001 < P < 0.05) except Ward's triangle. Vertebral fracture rates were 13/100 patient yr in the pamidronate group and 24/100 patient yr in those receiving placebo (P = 0.07), and there was a nonsignificant trend toward height loss being less in those receiving pamidronate (P = 0.16). It is concluded that pamidronate is an effective therapy in postmenopausal osteoporosis. PMID- 7989462 TI - Preparation and characterization of monoclonal antithyrotropin receptor antibodies obtained from peripheral lymphocytes of hypothyroid patients with primary myxedema. AB - Anti-TSH receptor antibodies (TSH-R Ab), which have been detected in the serum of some patients with primary myxedema, are themselves considered to induce hypothyroidism. These are termed blocking-type TSH-R Ab (TSH-R BAb), because they inhibit adenylate cyclase stimulation by TSH on thyrocytes or nonthyroidal cells transfected with TSH-R complementary DNA. We prepared monoclonal TSH-R BAb and characterized them. Peripheral lymphocytes from three patients with primary hypothyroidism and potent TSH-R BAb were transformed by Epstein-Barr virus, and the culture supernatants were screened by TSH binding inhibitor immunoglobulin (TBII) assay. Twenty positive and 7 negative lymphocyte clones were obtained; their monoclonality was confirmed by Southern blot analysis, using an immunoglobulin (Ig) JH probe. These monoclonal antibodies were then tested for TSH-R BAb activity. TSH-R BAb activity ranged from 24.1-58.5% (normal range, < 24%) in all 20 TBII-positive clones and in 2 of 7 TBII-negative clones. An enzyme linked immunosorbent assay showed that the Ig isotypes of these clones with TBII and/or TSH-R BAb activity were IgG in 8 and IgM in 14. Another enzyme-linked immunosorbent assay and Southern blot analysis of the light chains revealed that 13 clones had kappa-chains, whereas the light chains could not be determined in the other 9 clones. To summarize, 1) we obtained 22 clones that produced monoclonal TSH-R BAb, including 8 IgG-type clones. 2) The clones exhibited dominant usage of the kappa-chain. 3) Although all TBII clones had TSH-R BAb activity, their TBII and TSH-R BAb activities were not significantly correlated, and two TSH-R BAb clones did not show TBII activity. PMID- 7989463 TI - Procalcitonin increase after endotoxin injection in normal subjects. AB - As procalcitonin concentrations have been shown to be elevated in patients with septicemia and gram-negative infections in particular, we proceeded to investigate the effect of endotoxin, a product of gram-negative bacteria, on procalcitonin concentrations in normal human volunteers. Endotoxin from Escherichia coli 0113:H10:k, was injected i.v. at a dose of 4 mg/kg BW into these healthy volunteers. Blood samples were obtained before and 1, 2, 4, 6, 8, and 24 h after injection of the endotoxin. Each patient's cardiovascular and overall clinical status was monitored over this period. The patients developed chills and rigors, myalgia, and fever between 1-3 h. Tumor necrosis factor-alpha levels increased sharply at 1 h and peaked at 90 min, reaching the baseline concentration thereafter by 6 h. Interleukin-6 levels increased more gradually, peaking at 3 h and reaching the baseline concentration at 8 h. The procalcitonin concentration, which was undetectable (< 10 pg/mL) at 0, 1, and 2 h, was detectable at 4 h and peaked at 6 h, maintaining a plateau through 8 and 24 h (4 ng/mL). There was no elevation of calcitonin concentrations, which remained below 10 pg/mL, the lowest sensitivity of the assay. Procalcitonin was measured by a two-antibody immunoradiometric assay specific for this peptide, with no cross reactivity with calcitonin, katacalcin, or calcitonin gene-related peptide. We conclude that endotoxin induces the release of procalcitonin systemically, that this increase is not associated with an increase in calcitonin, and that the increase in procalcitonin associated with septicemia in patients may be mediated through the effect of endotoxin described here. Whether procalcitonin participates in the mechanisms underlying inflammation remains to be investigated. PMID- 7989464 TI - Circulating dihydroxyphenylglycol and norepinephrine concentrations during sympathetic nervous system activation in patients with pheochromocytoma. AB - Although increased plasma norepinephrine (NE) concentrations mediate vasoconstriction during episodic hypertension and hypertensive crises in patients with pheochromocytoma (Pheo), the precise origin of this circulating NE (tumor or sympathetic nerves) is not known. Dihydroxyphenylglycol (DHPG), a deaminated metabolite of NE, is formed principally in sympathetic nerve endings. Under basal conditions, plasma NE and DHPG concentrations correlate closely, and during sympathetic nervous system activation, both plasma NE and DHPG concentrations increase. This observation suggests that plasma DHPG concentrations may reflect the source of circulating NE (tumor or sympathetic nerves) during hypertensive episodes in patients with Pheo. Plasma NE and DHPG concentrations were measured simultaneously, and the NE/DHPG ratio was calculated in seven patients with Pheo during 20 min of sympathetic nervous system activation (treadmill exercise) before and after surgical resection of the tumor. Age- and sex-matched normal subjects were also studied. Exercise resulted in a significant increase in plasma NE and DHPG concentrations in patients with Pheo and in normal subjects (Pheo: basal NE, 1827 +/- 639; peak NE, 3016 +/- 769 pg/mL (P = 0.02); normal subjects: basal NE, 266 +/- 27; peak NE, 1166 +/- 197 pg/mL (P = 0.01); Pheo: basal DHPG, 1521 +/- 280; peak DHPG, 2313 +/- 252 pg/mL (P = 0.007); normal subjects: basal DHPG, 870 +/- 50; peak DHPG, 1630 +/- 180 pg/mL (P = 0.01)]. The NE/DHPG ratio increased with exercise in normal subjects (basal, 0.30 +/- 0.02; peak, 0.83 +/- 12; P = 0.005), but did not change in patients with Pheo (basal, 1.22 +/- 0.32; peak, 1.54 +/- 0.27). Exercise also increased plasma NE and DHPG concentrations and the NE/DHPG ratio in five patients studied after surgical resection of the tumor. Systolic blood pressure and heart rate increased significantly during exercise in all three study groups. The increase in plasma NE and HDPG concentrations during exercise-induced sympathetic nervous system stimulation in patients with Pheo is similar to that in normal subjects and may indicate that the sympathetic nervous system plays an important role in the pathogenesis of hypertension and hypertensive crises in patients with Pheo. PMID- 7989465 TI - Cholesteryl ester transfer protein gene: two common mutations and their effect on plasma high-density lipoprotein cholesterol content. AB - Cholesteryl ester transfer protein regulates high-density lipoprotein cholesterol (HDL-C) level, and genetic deficiency causes hyperalphalipoproteinemia (HALP). The G to A mutation in the intron 14 splice donor (I14A) has been known to be a common mutation in HALP. Recently, another mutant, D442G (Asp 442 to Gly), was ascertained. The allelic frequencies of I14A and D442G were investigated using 226 unrelated patients with HDL-C of 1.03 mmol/L (40 mg/dL) or greater. Of these, 44 had a mutation I14A and/or D442G. The I14A was found in 15, including 4 compound heterozygotes (I14A/D442G) in patients with HDL-C of 2.05 mmol/L (80 mg/dL) or greater. All I14A homozygotes (n = 5) were present in the group with HDL-C of 3.08 mmol/L (120 mg/dL) or greater, and the allelic frequency paralleled the increase in HDL-C level. D442G was identified in 33, including the 4 compound heterozygotes. Its allelic frequency appeared as two clusters, one at HDL-C around 1.79-2.03 mmol/L (70-79 mg/dL) and the other at HDL-C of 2.82 mmol/L (110 mg/dL) or greater; the latter consisted exclusively of compound heterozygotes. Allelic frequency in the general population for I14A and D442G was 0.81% and 4.62%, respectively. These data suggest that D442G is a common mutation and that, although I14A is responsible for the most severe HALP, D442G leads to a relatively smaller increase in HDL-C. PMID- 7989466 TI - Production and characterization of endothelin released by human endometrial epithelial cells in culture. AB - This study identified and characterized endothelin (ET) produced by human endometrial epithelial cells cultured under serum-free conditions, compared the ET released by cells derived from proliferative and secretory phase endometrium, and examined the regulation of ET released by these cells. ET messenger RNA was detected in normal human endometrium with maximal expression in the mid-late secretory phase. Immunoreactive ET released into culture media by separated endometrial epithelial and stromal cells was almost entirely of epithelial cell origin, consistent with the previous immunohistochemical findings. This was identified as ET-1 by reverse phase high-pressure liquid chromatography, and the fractionated conditioned media exhibited bioactivity similar to that of standard ET-1. Mean ET production was greater from cells derived from proliferative phase endometrium cultured either in serum (P < 0.02) or serum-free conditions (P < 0.02). Fetal calf serum stimulated ET-1 production from epithelial cells in a dose-responsive manner. ET production was also stimulated by transforming growth factor-beta 1 (2, 5 & 10 ng/mL) and IL-1 alpha (10 & 100 IU/mL) under serum-free conditions but always to a lesser extent than stimulation by serum. The production of ET in human endometrium underlines a potential role for ET in endometrial function. PMID- 7989467 TI - Dexamethasone therapy for isosexual precocious pseudopuberty caused by generalized glucocorticoid resistance. AB - Generalized glucocorticoid resistance presents with clinical features secondary to excess production of mineralocorticoids and adrenal androgens. It is our hypothesis that these clinical and biochemical features will respond to glucocorticoid therapy. We tested this hypothesis in a boy with generalized glucocorticoid resistance and increased adrenal androgens. Dexamethasone was administered from age 7 6/12 yr until the onset of true puberty at 11 0/12 yr. Serum concentrations of cortisol and adrenal androgens decreased to the normal or near normal range. The accelerated precocity improved. Secondary sex characteristics did not progress; the difference between bone age and chronological age decreased from 3 1/2 yr to 2 yr, and the difference between height age and bone age decreased from 2 yr to 1/2 yr. We conclude that dexamethasone is effective and safe therapy for the sexual precocity of generalized glucocorticoid resistance. PMID- 7989468 TI - A growth hormone/prolactin-binding protein in human milk. AB - In the course of studies of the distribution of GH-binding proteins (GHBP) in biological fluids, we identified a human (h) GH/hPRL-binding component in human milk. To characterize its nature, 16 human milk samples were analyzed by molecular exclusion chromatography after incubation with monomeric [125I]hGH. All samples showed a peak indicative of a hGH-containing complex with a mol wt of 52 kilodaltons (kDa)--considerably smaller than the high affinity GH-binding protein complex in plasma (80-85 kDa). Binding of [125I]hGH was inhibited in a dose dependent fashion by unlabeled hGH and to a lesser extent by hPRL, but not by oGH. Scatchard analysis yielded a Ka of 2.1 x 10(8) M-1 and a maximum binding capacity of 5.1 micrograms/L for hGH, and a Ka of 0.5 x 10(8) M-1 for hPRL. The derived molecular size of the milk GH/PRL-binding protein (BP) is 30 kDa, assuming 1:1 binding stoichiometry. The milk BP was not immunoprecipitable with any of 4 monoclonal antibodies directed against the hGH receptor or with a polyclonal antiserum directed against the hPRL receptor. The milk BP bound to hGH affinity columns, but unlike the GHBP in human plasma, did not bind to wheat germ lectin columns, suggesting different or no glycosylation. We conclude that human milk contains a high affinity GH/PRLBP that differs from the serum GHBP in its ligand specificity (binding both hGH and hPRL), molecular size, immunological, and glycosylation characteristics. Based on its immunochemical and ligand-binding characteristics, it does not appear to be a truncated GH receptor such as the plasma GHBP. Its lack of immunoreactivity with the one available antiserum also does not support its identity with a truncated PRL receptor. However, it cannot be excluded that the milk BP may represent a proteolytically or otherwise altered truncated form of the PRL receptor (or, less likely, the GH receptor) that maintains some binding activity, but has its immunological epitope(s) disabled. The precise nature and function of this protein remain to be defined. PMID- 7989469 TI - Racial differences in parathyroid hormone dynamics. AB - Elevations in PTH levels have been reported in black subjects. Such observations have not been consistent, however, and seem paradoxical in view of the known bone resorptive action of this hormone and the fact that black subjects have a higher bone mineral density and fewer fractures than their white counterparts. In this study, we used dynamic stimulation of the calcium-PTH axis to fully characterize potential racial differences in PTH dynamics. We, therefore, defined the inverse sigmoidal curve that describes the relationship between serum ionized calcium concentration and intact PTH levels in six normal white and six normal black volunteers and determined the four parameters that characterize this relationship. An elevation in any one of these parameters can result in hyperparathyroidism. Black subjects had higher maximal and minimal PTH responses to hypo- and hypercalcemia (mean intact PTH levels of 9.2 +/- 13 and 0.7 +/- 0.1 pmol/L respectively) than white subjects (6.9 +/- 0.6 and 0.3 +/- 0.1 pmol/L, respectively). There were no differences in the set-points or slopes of the curves. Despite the higher baseline and stimulated endogenous PTH levels in black subjects, their baseline and stimulated osteocalcin levels were lower. Our dynamic studies, therefore, document mild hyperparathyroidism in black subjects and suggest mild skeletal resistance to PTH. PMID- 7989470 TI - Variant sequences of insulin receptor substrate-1 in patients with noninsulin dependent diabetes mellitus. AB - The pathophysiology of noninsulin-dependent diabetes mellitus (NIDDM) is characterized by insulin resistance and insulin deficiency. To search for genetic defects causing NIDDM, we have screened for mutations in the gene encoding insulin receptor substrate-1 (IRS-1), an intracellular protein that is phosphorylated by the insulin receptor and is thought to play an important role in mediating insulin action. The coding sequence of the IRS-1 gene (divided into 12 overlapping fragments) was amplified by polymerase chain reaction and screened for the presence of single stranded conformational polymorphisms. This led to the identification of 6 variants in the nucleotide sequence. There were 3 nonconservative amino acids substitutions: Gly819-->Arg, Gly972-->Arg, and Arg1221-->Cys. In addition, there were three silent polymorphisms: GAC vs. GAT encoding Asp90, GGG vs. GGA encoding Gly235, and GCA vs. GCG encoding Ala805. The previously reported Arg972 substitution was identified in 7 of 31 patients with NIDDM, 4 of 32 normal subjects, and 4 of 16 nondiabetic obese individuals. The 2 novel amino acid substitutions (Arg819 and Cys1221) were both detected in 1 patient with NIDDM, but not in either of the other 2 groups of nondiabetic individuals. All 3 amino acid residues are identically conserved in the amino acid sequences of human, mouse, and rat IRS-1, suggesting that Gly819, Gly972, and Arg1221 are important for the normal function of IRS-1. Furthermore, the prevalence of amino acid substitutions in IRS-1 is increased in patients with NIDDM. These observations suggest that mutations in the IRS-1 gene may play a causal role in the pathogenesis of NIDDM. PMID- 7989471 TI - Frequency of severe hypoglycemia in insulin-dependent diabetes mellitus can be predicted from self-monitoring blood glucose data. AB - Severe hypoglycemia is associated with insulin-dependent diabetes mellitus and may occur more frequently as metabolic control approaches normal. The goal of this study was to determine whether the frequency of severe hypoglycemia could be predicted by the following predictor variables: 1) frequency and degree of low blood glucose (BG) readings, 2) degree of BG variability during routine self monitoring blood glucose (SMBG) readings, and 3) level of glycemic control measured by glycosylated hemoglobin-A1 (HbA1). Seventy-eight insulin-dependent diabetes mellitus subjects from 3 different sites had their glycosylated HbA1 assayed and then performed 50 SMBG recordings during the next 2-3 weeks. Over the following 6 months, subjects recorded their severe hypoglycemic episodes (stupor or unconsciousness). There was no difference in the number of severe hypoglycemic episodes between subjects in good vs. poor metabolic control. A higher frequency of severe hypoglycemia during the subsequent 6 months was predicted by frequent and extreme low SMBG readings and variability in day to day SMBG readings. Regression analysis indicated that 44% of the variance in severe hypoglycemic episodes could be accounted for by initial measures of BG variance and the extent of low BG readings. Patients who recorded variable and frequent very low BG readings during routine SMBG were at higher risk for subsequent severe hypoglycemia. Individuals who had lower glycosylated Hb levels were not at higher risk of severe hypoglycemic episodes. PMID- 7989472 TI - Value and limits of pharmacological and physiological tests to diagnose growth hormone (GH) deficiency and predict therapy response: first and second retesting during replacement therapy of patients defined as GH deficient. AB - There is currently a debate about the use of pharmacological and physiological tests to define GH deficiency and predict response to GH therapy. In addition, a good response to therapy has also been described in subjects without GH deficiency. For further information, we reevaluated GH secretion during replacement therapy in a group of children defined as GH deficient and examined response to therapy in the subjects subdivided according to secretion. One hundred eighty four children (113 boys and 71 girls) initially diagnosed with GH deficiency by means of pharmacological (peak < 8 micrograms/L after arginine and L-dopa tests) and physiological tests (mean nocturnal concentration < or = 3.3 micrograms/L during sleep test) underwent the same tests 2.8 +/- 1.1 yr after start of GH therapy. Sixty eight patients were retested 1.5 +/- 0.4 yr after first retesting. At diagnosis 122 subjects had pathological pharmacological and physiological tests (group A), 30 subjects normal sleep test with pathological pharmacological tests (group B), and 32 subjects pathological sleep test with normal pharmacological tests (group C). At diagnosis 140 subjects were prepubertal and 44 pubertal. To evaluate response to therapy in relation to GH secretion at diagnosis and at both retestings, a number of auxological parameters were calculated during treatment. At first retesting, 107 subjects (58.1%) changed initial group of diagnosis, 34 of whom (18.5%) presented normal secretion in both pharmacological and physiological tests (group D). At second retesting, 31 of the 68 subjects reexamined (45.6%) changed first test results, and 33 (48.5%) reverted to the initial group of diagnosis; none of the 6 subjects of group D maintained normal secretion. Although the percentage of normalized subjects was higher in pubertal subjects (36.4%; P = 0.0003) than prepubertal subjects (8.9%), puberty did not prevent a reduction of secretion in some subjects. Response treatment during the first year of therapy was similar in the various groups. GH secretion seems to change in both prepubertal and pubertal children diagnosed with GH deficiency when pharmacological and physiological tests are repeated over time. Moreover, such tests may not represent a reliable tool for predicting response to treatment. GH secretion normalization at retesting may not necessarily represent the end of a transient secretory defect. PMID- 7989473 TI - Regulation of inhibin alpha- and beta A-subunit messenger ribonucleic acid levels by chorionic gonadotropin and recombinant follicle-stimulating hormone in cultured human granulosa-luteal cells. AB - We studied the effects of recombinant human FSH (rhFSH) and purified hCG on the steady state messenger ribonucleic acid (mRNA) levels of inhibin alpha- and beta A-subunits in cultured granulosa-luteal cells of preovulatory ovarian follicles obtained from women undergoing in vitro fertilization. Specific mRNA transcripts for the alpha- and beta A-subunits were detected in Northern and dot blot filter hybridization analyses, and the levels of these mRNAs were induced by rhFSH and hCG in a distinct concentration- and time-dependent manner. The basal and hCG stimulated alpha-subunit mRNA levels were first determined at 2- to 3-day intervals over a 3- to 10-day culture period after the initiation of the cultures. Both the basal and hCG-stimulated alpha-subunit mRNA levels declined steadily during culture, but the maximal relative stimulatory effect of hCG was observed on day 7 of culture. All subsequent experiments, therefore, were performed on days 6-8 of culture. Both gonadotropins induced alpha-subunit mRNA levels with slower kinetics than those of the beta A-subunit. Varying between experiments, rhFSH and hCG increased the expression of the alpha-subunit with a maximal effect of 2.5- to 5.7-fold and 1.7- to 7.2-fold, respectively, above basal levels 24-48 h after stimulation. rhFSH and hCG induced beta A-subunit mRNA levels with 3.0- to 5.8-fold and 2.3- to 8.6-fold increases above basal levels, respectively, at 2 h; thereafter, only moderate or no stimulation of the beta A subunit mRNA levels could be detected at 7-48 h. Treatment of the cells with the RNA synthesis inhibitor actinomycin-D prevented the induction of alpha-subunit mRNA levels by hCG, and no significant differences were detected in the stability of alpha-subunit mRNA transcripts in hCG-treated cells vs. untreated cultures. This indicates that hCG induces transcription of the alpha-subunit gene rather than maintains the levels of preexisting transcripts. As the kinetics of induction of alpha- and beta A-subunit mRNAs by gonadotropins were different, we examined how the inhibition of protein synthesis affects the induction of alpha- and beta A-subunit mRNAs by hCG. Cycloheximide had no effect on basal alpha subunit mRNA levels at 2 or 24 h. However, it inhibited at 24 h the induction of the alpha-subunit by hCG.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 7989474 TI - Spontaneous growth hormone (GH) secretion by unstimulated human lymphocytes and the effects of GH-releasing hormone and somatostatin. AB - We investigated in five normal subjects whether the secretion of GH from lymphocytes would occur spontaneously without mitogens and be regulated by GHRH and somatostatin as in the endocrine system. Peripheral blood mononuclear cells were isolated from heparinized blood by the standard Ficoll-Hypaque gradient centrifugation method, and incubated for up to 7 days with or without GHRH, somatostatin analog (SMS 201-995), cycloheximide, or actinomycin D. GH levels in the lyophilized samples were measured by a highly sensitive enzyme immunoassay. GH concentration in culture medium (5 x 10(5) cells/mL) time dependently increased in all subjects, reaching 0.47 +/- 0.18 ng/L at day 7. A protein synthesis inhibitor (cycloheximide) and RNA synthesis inhibitor (actinomycin D) completely blocked GH secretion from lymphocytes. Immunoreactive GH secreted by unstimulated human lymphocytes was similar to pituitary GH in terms of antigenicity and molecular weight. Physiological concentrations of GHRH (10(-10) 10(-8) mol/L) and SMS 201-995 (10(-8)-10(-6) mol/L) had no effects on the spontaneous secretion of GH from human lymphocytes. These results indicate that GH is spontaneously synthesized de novo and secreted from unstimulated human lymphocytes, and that the regulation of GH in the immune system differs from that in the endocrine system. PMID- 7989475 TI - Obstructive sleep apnea in obese noninsulin-dependent diabetic patients: effect of continuous positive airway pressure treatment on insulin responsiveness. AB - Patients with noninsulin-dependent diabetes mellitus (NIDDM) are often obese and frequently complain of tiredness. These features are also characteristically seen in patients with obstructive sleep apnea (OSA). Therefore, it was the aim of this study to assess the prevalence of OSA among a group of obese NIDDM patients who have some clinical features of OSA. The effect of reversal of OSA by nasal continuous positive airway pressure (CPAP) treatment on insulin responsiveness was also investigated. From a population of 179 NIDDM patients with a body mass index (BMI) greater than 35 kg/m2, we performed ambulatory sleep monitoring on 31 (15 males and 16 females) who admitted to either heavy snoring or excessive sleepiness. Results were reviewed by a sleep physician blinded to the clinical status of the patients, and 22 (70%) were found to have moderate or severe OSA, with mean oxygen desaturation indexes of 10.3 +/- 5.3 and 30.7 +/- 13.2 episodes/h, respectively. A subgroup of 10 patients (seven males and three females) with a mean BMI of 42.7 +/- 4.3 kg/m2 was treated with nightly CPAP for 4 months. These subjects all had significant OSA, with frequent obstructive apneas (mean, 47 +/- 31.6 episodes/h) and oxygen desaturation (mean minimum O2 saturation, 74 +/- 9.5%), as determined by polysomnography. One patient was excluded from analysis because of infrequent use of CPAP. Insulin responsiveness in terms of glucose disposal measured by hyperinsulinemic euglycemic clamps improved from 11.4 +/- 6.2 to 15.1 +/- 4.6 mumol/kg.min (P < 0.05) during CPAP treatment. These results indicate that OSA occurs commonly in obese NIDDM patients with excessive sleepiness or heavy snoring. Treatment of their OSA may improve insulin responsiveness. PMID- 7989476 TI - Studies of the nature of 17-hydroxyprogesterone hyperresonsiveness to gonadotropin-releasing hormone agonist challenge in functional ovarian hyperandrogenism. AB - Plasma 17-hydroxyprogesterone (17PROG) hyperresponsiveness to GnRH agonist (nafarelin) testing is typical of polycystic ovary syndrome and other functional ovarian hyperandrogenism (FOH) that does not meet customary criteria for the diagnosis of polycystic ovary syndrome. We have postulated that this results from abnormal regulation of androgen secretion. Whether this dysregulation is the result of a normal physiological response to ovarian hyperstimulation or escape from down-regulation of steroidogenesis is unknown. To distinguish between these possibilities, we have analyzed the ovarian steroid responses to nafarelin for the apparent efficiency of the steroidogenic steps and the apparent dose-response relationships between blood LH and steroid levels. We compared normal women (n = 18) with three groups of hyperandrogenic women (n = 15-19/group): patients with 17PROG hyperresponsiveness with or without elevated LH levels (type 1 and type 2 FOH, respectively) and patients with normal 17PROG responses to nafarelin (nafarelin negative). Subjects were pretreated with dexamethasone to suppress coincidental adrenal contributions to plasma steroid levels. The pattern of steroid secretion was similarly abnormal in both types of FOH, with the high LH group having generally more severe abnormalities in the levels of steroid intermediates. Baseline 17PROG and 17-hydroxypregnenolone and the ratio of 17PROG to androstenedione (AD) were increased (P < 0.05). In addition, the apparent slope of the 17PROG response to LH was significantly increased. Baseline levels of both AD and dehydroepiandrosterone and the AD response to nafarelin were increased, yet the ratio of peak minus baseline (delta) AD/delta 17PROG (another index of 17,20-lyase activity) was subnormal in FOH. The apparent slope of the testosterone (T) response to LH was significantly increased, and indexes of aromatase activity [estradiol (E2)/T and delta estradiol/delta T] were significantly decreased. Nafarelin stimulated plasma E2 in all groups to rise along an apparently similar LH-E2 dose-response slope. We interpret these results as indicating that FOH patients have generalized overactivity of thecal steroidogenesis, but nevertheless compensate so as to maintain a normal dose response relationship between blood levels of LH and E2. FOH patients, whether they have LH excess or not, seen to form excessive 17PROG and incompletely dampen (down-regulate) thecal cell 17PROG, AD, and T secretion in response to LH stimulation. 17PROG hyperresponsiveness to nafarelin seems to be prominent both because it is formed in excess and because 17,20-lyase efficiency is rate limiting. The T elevation seems to arise mainly from overactive steroidogenesis, but also partly from an additional functional decrease in aromatase efficiency, which is secondary to negative feedback by the substrate-driven tendency toward estrogen excess.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 7989477 TI - Comparison of new biochemical markers of bone turnover in late postmenopausal osteoporotic women in response to alendronate treatment. AB - To evaluate the clinical utility of recently developed biochemical markers of bone turnover to monitor the response of osteoporotic patients to antiresorptive therapy, we compared the results of three advanced assays for markers of bone resorption and four of bone formation to high pressure liquid chromatography (HPLC)-fluorometric assays for urinary pyridinoline and deoxypyridinoline. These assays were also used to resolve the uncertainties concerning the rate of bone turnover in late postmenopausal (late-PMP) osteoporotic women. The rate of bone turnover in 85 women (mean +/- SD age, 63 +/- 6 yr) with low bone mass and all more than 5 yr postmenopausal (mean +/- SD yr PMP, 16 +/- 7 yr) was compared to that in 46 premenopausal women (mean +/- SD age, 40 +/- 5 yr) randomly selected from a large cohort and all having a normal spine bone mineral density (BMD). The late-PMP osteoporotic patients were a subset of patients enrolled in a double blind, placebo-controlled, randomized study comparing the effects of several doses of oral alendronate, a potent and specific inhibitor of bone resorption. Periodically during the 2-yr study, the women's spinal BMD and the level of several markers of bone turnover were measured. Serum total and intact osteocalcin, bone-specific alkaline phosphatase, and carboxy-terminal propeptide of type I collagen measured by RIA were used to assess bone formation. To assess bone resorption, we measured the urinary excretion of total pyridinoline (HPLC Pyr) and deoxypyridinoline (HPLC D-Pyr) by HPLC, type I collagen cross-linked N telopeptide and urinary free PYR (F-Pyr) by enzyme-linked immunosorbent assay, and the serum concentration of type I collagen cross-linked C-telopeptide (ICTP) by RIA. All bone formation markers, except carboxy-terminal propeptide of type I collagen, and all bone resorption markers, except ICTP, were significantly increased above normal (33-171%; P < 0.001) in late-PMP osteoporotic women. The long term within-patient variability assessed over a 15-month period in the placebo group was low and was somewhat lower for serum markers (12.5-17.4%) than for urinary markers (24-29%). Under treatment with alendronate, resorption markers decreased earlier than markers of bone formation, consistent with a direct action of the drug to inhibit osteoclastic bone resorption. With the exception of F-Pyr and ICTP, the levels of bone markers were reduced to the normal premenopausal range, and this steady state was maintained from 6-15 months.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 7989478 TI - Altered parathyroid gland function in severely immunocompromised patients infected with human immunodeficiency virus. AB - Several endocrine functions have been found disturbed in patients with acquired immunodeficiency syndrome (AIDS). However, no information is available on parathyroid function in these patients. Six patients with AIDS and 10 healthy volunteers underwent an EDTA infusion to induce hypocalcemia and stimulate PTH secretion. A group of 6 severely ill patients with malignancies was studied at baseline and served as additional controls for the effect of a severe disease per se. Baseline values showed that mean serum intact PTH concentration was lower in patients infected with the human immunodeficiency virus than in healthy volunteers (P < 0.04) as well as in patients with malignancies (P = 0.004). Whole blood calcium also tended to be lower in patients with the human immunodeficiency virus than in both control groups, the difference reaching the limit of statistical significance for the healthy controls only (P < 0.04). Mean serum magnesium, 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D concentrations were similar in both groups. Throughout the entire EDTA stimulation procedure, i.e. at any blood calcium concentration, serum intact PTH concentration remained lower in patients with AIDS than in healthy control subjects (P < 0.04, analysis of variance for repeated measurements). Basal and maximal secretion of PTH is reduced in patients with AIDS. The mechanisms underlying this finding remain speculative. PMID- 7989479 TI - Growth hormone secretion in recently operated acromegalic patients. AB - GH secretion patterns were studied in 14 recently transsphenoidally operated patients by measuring GH concentrations in blood sampled every 10 min over 24 h with a highly sensitive time-resolved immuno-fluorescent assay. Plasma GH concentrations were analyzed with a discrete peak detection program (Cluster) and a multiparameter deconvolution technique. Diurnal variations were analyzed by cosinor analysis. Nine or 10 days after pituitary surgery all patients had a normal plasma insulin-like growth factor-I level, and GH levels were suppressed to below 1.25 micrograms/L in 13 patients and to 1.3 micrograms/L in 1 subject during an oral glucose tolerance test. As we found a highly significant difference in GH secretion between male and female controls, the results obtained in patients were compared with those in their gender- and age-matched controls. Patients with active acromegaly displayed a significantly higher number of deconvolution-estimated secretory bursts (31/24 h in males and 27/24 h in female patients). The estimated secretion rate per 24 h was 25 times greater in female acromegalics and 100 times greater in male acromegalics than that in the controls. In patients with active acromegaly, about 50% of the GH was secreted in a nonpulsatile fashion. In contrast, normal subjects and patients shortly after pituitary surgery secreted GH predominantly (> 99%) in a pulsatile manner. By deconvolution analysis, the mean plasma half-life of GH was 19.7 min in treated male patients and 19.5 min in treated female patients (P = NS vs. controls) estimated mean total GH production/day, 188 micrograms in males and 240 micrograms in females (P = NS vs. controls); number of secretory bursts/24 h, 19.3 in males and 21.9 in females (P = NS vs. controls). In addition, we could not establish any difference in pulse characteristics with Cluster analysis between surgically treated patients and their control subjects. The present data suggest that the basic abnormality of acromegaly resides in the pituitary gland rather than in the hypothalamus. PMID- 7989481 TI - Renin in Wilms' tumor: prorenin as an indicator. AB - In a prospective study, 25 children with nephroblastoma (Wilms' tumor) had preoperative plasma prorenin and renin concentrations measured. The mean plasma renin and prorenin concentrations in the patients were raised compared with a control group of patients without nephroblastoma. Four children had recurrence of tumor and, in three, this was associated with an increase in plasma prorenin concentration. Nephroblastoma tissue contained immunoreactive renin and renin messenger RNA, and the renin protein was immunologically and biochemically similar to normal human renin. We conclude that prorenin concentrations in plasma are an indicator of nephroblastoma. PMID- 7989480 TI - Sequential estrogen-progestin addition to gonadotropin-releasing hormone agonist suppression for the chronic treatment of ovarian hyperandrogenism: a pilot study. AB - The purpose of the study was to evaluate the efficacy and safety of a sequential regimen of estrogen-progestin addition to GnRH agonist suppression in ovarian hyperandrogenism. Eight patients presenting with a polycystic ovary syndrome were treated with an sc implant of GnRH agonist every 4 weeks for 48 weeks. Starting at week 9, patients were replaced with 100 micrograms transdermal estradiol patches continuously and sequentially combined with 10 mg oral medroxyprogesterone acetate the last 2 weeks of each 4-week period. The rapid down-regulation of the pituitary-ovarian axis led to significant reduction of testosterone and androstenedione to 48.9% and 67.4% of baseline, respectively. During steroid replacement, testosterone and androstenedione continued to decrease gradually. The baseline hirsutism score (18.7 +/- 1.3) progressively fell to 9.7 +/- 2.0 at the end of treatment. The mean hair diameter was significantly reduced (0.097 +/- 0.004 vs. 0.081 +/- 0.005 mm). A withdrawal bleeding was obtained in 63.6% of the artificial cycles, but breakthrough bleeding occurred during 48% of the sequential replacements. The incidence of menopausal symptoms was low. There was a nonsignificant decrease in bone mineral content of the lumbar spine and the femoral neck but no trend in Ca2+/creatinine and OH-proline (OH-P)/creatinine ratios or in serum triglycerides and cholesterol fractions. There was a nonsignificant increase in hirsutism score in five patients followed up for 24 weeks after cessation of treatment, although there was a rapid return of hormones toward baseline and recurrence of irregular bleeding. Transdermal estradiol addition periodically combined with medroxyprogesterone acetate is effective in reducing hirsutism and is safe in minimizing side effects and bone loss. A regimen allowing a better bleeding control would make this approach a valuable alternative for prolonged or repeated palliative treatment of excessive hair growth and irregular bleeding in polycystic ovary syndrome. PMID- 7989482 TI - Different lipid contents between aldosterone-producing and nonhyperfunctioning adrenocortical adenomas: in vivo measurement using chemical-shift magnetic resonance imaging. AB - Lipid contents in the 11 aldosterone-producing and 24 nonhyperfunctioning adrenocortical adenomas and 8 pheochromocytomas were assessed in vivo by using chemical-shift fast low-angle shot magnetic resonance imaging. T2 relaxation times were measured by using a spin echo sequence. The relative lipid contents of pheochromocytomas were significantly less than adrenocortical adenomas. The relative lipid contents of aldosterone-producing adenomas were significantly less than nonhyperfunctioning adenomas. The longer T2 relaxation times of aldosterone producing adenomas may also represent less lipid contents compared with nonhyperfunctioning adenomas. These results strongly support the suggestion that there is a very close relationship between accumulated lipid droplets and functional aspects in the adrenocortical cells. Chemical-shift magnetic resonance imaging may be a useful method for the indirect analysis of the function of adrenocortical adenomas in vivo. PMID- 7989483 TI - Differential responses of biologically active luteinizing hormone secretion in older versus young men to interruption of androgen negative feedback. AB - To investigate the responsiveness of the healthy aging male hypothalamo-pituitary gonadal axis to short term interruption of androgen negative feedback, we administered a selective nonsteroidal competitive antagonist of the androgen receptor, flutamide hydrochloride (250 mg, orally, three times daily for 3.5 days), to five older (aged 63-72 yr) and eight young (aged 21-30 yr) men. Pulsatile bioactive LH release was assessed by the rat interstitial cell testosterone bioassay in plasma sampled at 10-min intervals for 8 h overnight at baseline and after flutamide administration. Pituitary responsiveness was evaluated after two successive i.v. injections of 10 micrograms GnRH. Deconvolution analysis was used to estimate the number, amplitude, duration, and mass of bioactive LH secretory bursts and the half-life of biologically active hormone. At baseline, older men exhibited a significantly lower spontaneous bioactive LH secretory burst frequency than young men, with a median of 5 events/8 h (older) vs. 7.5 bursts/8 h (younger, P < 0.05). In older men, mean 8-h plasma bioactive LH concentrations increased significantly in response to flutamide (P = 0.006), and the 8-h calculated secretion rate of bioactive LH rose concomitantly. These increases were similar to responses in young men. However, during antiandrogen administration, the frequency of bioactive LH secretory bursts failed to rise in older men to the baseline value seen in young men. Moreover, older (but not young) men showed a significant prolongation of the LH secretory burst duration in response to flutamide treatment. On the other hand, the estimated half-life of endogenous bioactive LH increased significantly after flutamide ingestion in young compared to older individuals. After GnRH injections, older and young men secreted similar amounts of LH before flutamide administration, but during flutamide treatment, older men released more biologically active LH after the first GnRH stimulus [older men, 104 +/- 11 IU/L (median, 110); younger men, 44 +/- 8.4 IU/L (median, 40); P < 0.05]. Serum free testosterone concentrations rose significantly during flutamide exposure in both young and older men, but estradiol concentrations increased significantly only in young men. In summary, healthy older men exhibit a reduced (overnight) spontaneous bioactive LH secretory burst frequency. Pharmacological attenuation of androgen-mediated negative feedback increases mean serum free testosterone concentrations and plasma bioactive LH concentrations to a similar degree in older and young individuals, but different mechanisms operate in the two age groups. In older men, flutamide treatment amplifies the mass of bioactive LH secreted per burst by prolonging the LH secretory burst duration, whereas in young men, flutamide administration increases the apparent half-life of biologically active LHG significantly relative to values in older men. We conclude that competitive nonsteroidal blockade of the androgen receptor unmasks qualitatively altered mechanisms of increased bioactive LH release in healthy older men. PMID- 7989484 TI - Source localization of androgen excess in adolescent girls. AB - Functional ovarian hyperandrogenism (FOH) is characterized by an abnormal ovarian response to challenge with the GnRH analogs nafarelin and leuprolide acetate, similar to that observed in women with well defined polycystic ovary syndrome, regardless of whether elevated LH levels or polycystic ovaries are present. We studied an unselected group of 42 hyperandrogenic adolescents (age range, 14-22 yr; mean, 18.1 +/- 2.5 yr) 1) to determine FOH incidence through the assessment of ovarian-steroidogenic response to a single dose of leuprolide acetate, 2) to assess the clinical characteristics of patients according to their responses to GnRH analog stimulation, and 3) to evaluate adrenal steroidogenic function and its relation to ovarian hyperandrogenism in patients with either normal or abnormal responses to leuprolide acetate challenge. All patients underwent leuprolide acetate and ACTH testing, dexamethasone and ovarian suppression tests, and pelvic ultrasonography. Twenty-four (58%) patients had supranormal plasma 17 hydroxyprogesterone (17-OHP) responses to leuprolide acetate characteristic of FOH, and in 18, the 17-OHP response was similar to that of controls (n = 24; age, 17.1 +/- 2.3 yr). Seven patients (5 with FOH and 2 with normal responses to leuprolide acetate) had an abnormal response to ACTH, but only 1 had conclusive evidence of 21-hydroxylase deficiency. In 16 patients, the response to both stimulation tests was normal. Only 13 (54%) of the 24 FOH patients had polycystic ovaries on ultrasonography, and in 11 (46%), basal plasma LH levels were elevated. In FOH patients, reduction in testosterone and androstenedione plasma levels was significantly greater after ovarian suppression than after dexamethasone challenge (P < 0.0005 and P < 0.02, respectively). Peak plasma 17 OHP levels postleoprolide acetate simulation correlated with dexamethasone suppressed plasma testosterone concentrations, dexamethasone-suppressed plasma androstenedione levels, and the free androgen index postdexamethasone treatment (r = 0.4, P = 0.01; r+ 0.4, P < 0.05; and r = 0.41, P = 0.007, respectively), Plasma sex hormone-binding globulin levels after dexamethasone administration correlated negatively with the baseline free androgen index (r = -.0.67; P < 0.0001). Considering our diagnostic criteria, 26 (62%) of our collective of 42 patients had abnormal responses to one or both stimulation tests, whereas 16 (37%) had normal response. FOH is the most common cause in (58%) of androgen excess in adolescence. Short term leuprolide acetate stimulation is a reliable tool fro identification of the ovary as the source of their hyperandrogenism. PMID- 7989485 TI - Identification and functional characterization of two new somatic mutations causing constitutive activation of the thyrotropin receptor in hyperfunctioning autonomous adenomas of the thyroid. AB - It has recently been shown that somatic and germ line mutations of the TSH receptor gene cause autonomous hyperfunctioning thyroid adenomas and nonautoimmune toxic thyroid hyperplasia by constitutive activation of the TSH receptor. A "saturated" map of these mutations is a prerequisite for a systematic screening for these clinically important mutations. In this context, it is also of interest to determine whether different amino acid substitutions at the same residue cause constitutive activation of the TSH receptor, as suggested by site directed mutagenesis of the alpha 1 beta-adrenergic receptor. We, therefore, screened further hyperfunctioning autonomous adenomas of the thyroid for constitutively activating mutations. We identified two new somatic mutations, changing alanine in position 623 to valine (A623V) and threonine in position 632 to isoleucine (T632I). Both mutations constitutively activated cAMP when transiently expressed in COS cells. Together with neighboring mutations, the T632I mutation demonstrates the importance of transmembrane domain VI for the activation of the TSH receptor and characterizes it as a hot spot for constitutively activating mutations. The previously identified A623I and the newly identified A623V mutations demonstrate that several amino acid substitutions at the same residue can cause constitutive activation of the TSH receptor. PMID- 7989486 TI - Baboon corpus luteum: autonomous pulsatile progesterone secretion and evidence for an intraluteal oscillator demonstrated by in vitro microretrodialysis. AB - Pulsatility of serum progesterone (P) is usually ascribed to stimulation of the corpus luteum (CL) by pulsatile release of pituitary LH. We investigated P secretion by the primate CL by performing microretrodialysis on 6 fresh CL obtained at laparotomy from baboons (Papio anubis) with well defined menstrual cycles. Individually microdialyzed for 24-26 h with Dulbecco's Modified Eagle's Medium and Ham's F-12 enriched with HEPES buffer in a perifusion chamber, the retrodialyzed fluid was collected every 10 min and measured for P, estradiol, and 17 alpha-hydroxyprogesterone by specific and sensitive RIAs. The chronodynamics of hormone secretion were analyzed for pulse detection by PC-Pulsar 3.0. All 6 CL (2 each from early, LH +1 to +5; mid, LH +6 to +10; and late luteal phases, LH +11 to +15) demonstrated pulsatile secretion of P in vitro, with distinct and detectable peaks over the 24-26 h studied. The CL secreted 23-27 pulses of P in 24 h in early luteal, 8-20 pulses in midluteal, and 6-19 pulses in late luteal phases. Peak lengths were 23.8 +/- 18.5 to 35.7 +/- 17.1 min. Four CL gave interpeak intervals of 46-55 min, whereas two gave intervals of 136-137 min. Analysis of distribution of pulses against different interpulse intervals in individual CL and all CL together revealed a bell-shaped distribution, with the largest number of pulses seen at an interpulse interval of 21-40 min. Because of the low concentrations of estradiol and 17 alpha-hydroxyprogesterone retrodialyzed, a similar analysis of these data was not possible. Histological examination of the tissue at the termination of the experiment using hematoxylin and eosin and localization of 3 beta-hydroxysteroid dehydrogenase activity indicates that the steroidogenic potential of the tissue is minimally affected, although some morphological changes do occur. Our findings suggest autonomous pulsatile P secretion by the primate CL, indicating local control by and the presence of an intraluteal oscillator or pulse generator for P secretion. PMID- 7989487 TI - Abnormal temporal patterns of glucose tolerance in obesity: relationship to sleep related growth hormone secretion and circadian cortisol rhythmicity. AB - To define the chronobiology of glucose tolerance and insulin secretion in obesity, nine obese men and nine lean men were studied during constant glucose infusion for 53 h, including 8 h of nocturnal sleep, 28 h of continuous wakefulness, and 8 h of daytime sleep. Blood samples were collected at 20-min intervals to assay glucose, insulin, C-peptide, cortisol, and GH. Sleep was polygraphically monitored. Abnormal temporal profiles of glucose regulation were observed during wakefulness and sleep in obese subjects. During daytime hours, the normal profile of glucose tolerance was reversed, as an improvement, rather than a deterioration, was observed from morning to late evening. This reversal of the daytime pattern appeared to be caused by a dual defect in glucose regulation during the previous night. Indeed, during early sleep, GH secretion was markedly reduced, and the nocturnal rises of glucose and insulin secretion were dampened. During late sleep, obese subjects failed to suppress insulin secretion and plasma glucose, resulting in high morning levels. Comparisons of metabolic and hormonal patterns during nocturnal and daytime sleep suggest that the failure to suppress insulin secretion in late sleep may reflect a relative insensitivity of the beta cell to acute inhibitory effects of cortisol in addition to insulin resistance. PMID- 7989488 TI - Disproportionately increased proinsulin levels are associated with the insulin resistance syndrome. AB - Recent data suggest that proinsulin may be associated with increased cardiovascular risk factors in both diabetic and nondiabetic subjects. We examined the relation of insulin, proinsulin, and the fasting proinsulin/insulin ratio to a number of metabolic disorders believed to be related to the insulin resistance syndrome (low high density lipoprotein cholesterol and high triglyceride levels, hypertension, and impaired glucose tolerance). Proinsulin was measured by a RIA, and insulin was measured by a Linco RIA that does not cross-react with proinsulin. The increased fasting proinsulin/insulin ratio was significantly associated with hypertension, low high density lipoprotein cholesterol and high triglyceride levels, and impaired glucose tolerance in 423 nondiabetic subjects. The fasting proinsulin/insulin ratio increased significantly with the number of metabolic disorders (zero, 0.060; one, 0.086; two, 0.098; three, 0.177; four, 0.182; P < 0.001). The increased proinsulin/insulin ratio was also associated with a greater number of metabolic disorders in diabetic subjects. Our results show that particularly nondiabetic individuals with the insulin resistance syndrome not only have hyperinsulinemia as a marker of insulin resistance, but also show an increase in proinsulin relative to insulin, which may reflect relative beta-cell failure or malfunction. PMID- 7989489 TI - No evidence of mutations in the genes for type I and type II 3 beta hydroxysteroid dehydrogenase (3 beta HSD) in nonclassical 3 beta HSD deficiency. AB - Nonclassical 3 beta-hydroxysteroid dehydrogenase/delta 5-delta 4-isomerase deficiency (NC3 beta HSDD) has been diagnosed in hyperandrogenic women with an increasing frequency during the last 14 yr. Fifteen menarcheal women with androgen excess syndrome, diagnosed with NC3 beta HSDD previously were restudied, in 12 after discontinuation of glucocorticoid treatment, in 2 patients never treated with glucocorticoids, and in 1 both before and after glucocorticoid therapy. Each of the 15 patients underwent ACTH stimulation testing, in some cases on multiple occasions. Although some (very few) patients seem to have improved with time, others remained the same or got worse. Molecular DNA analysis was also performed in 6 of the patients, using the strategy successfully used to detect point mutations in the type II 3 beta-hydroxysteroid dehydrogenase (3 beta HSD) gene, which are responsible for classical 3 beta HSD deficiency. This strategy consists of the direct sequencing of polymerase chain reaction-amplified DNA fragments corresponding to the complete coding sequence and all intron-exon junctions and to the 5'- and 3'-noncoding region of this gene. We were unable to demonstrate any mutation of the type II 3 beta HSD gene in these 6 patients. To gain additional information about potential mutations, direct sequencing of the type I 3 beta HSD gene was also performed using this same strategy, and no mutations were found. The present study strongly suggests that unlike the salt losing and nonsalt-losing forms of classical 3 beta HSD deficiency, NC3 beta HSDD is not due to a mutant type II 3 beta HSD enzyme. However, the possibility remains of a mutation(s) in the unsequenced regions of the type II 3 beta HSD gene or elsewhere, such as in a gene for modulatory protein, playing a specific role in the expression of the type II 3 beta HSD gene. On the other hand, knowing the multiple hormonal controls to which 3 beta HSD activity is subject, it cannot be excluded that at least in some cases, NC3 beta HSDD may be an acquired defect, the result of endogenous or environmental factors. PMID- 7989490 TI - CYP19 (aromatase cytochrome P450) gene expression in human malignant endometrial tumors. AB - C19 steroids are converted to estrogens in a number of human tissues by the aromatase enzyme complex, which consists of aromatase cytochrome P450 (P450arom; product of the CYP19 gene) and NADPH-cytochrome P450 reductase. Aromatase activity has been previously demonstrated in endometrial tumors. In the present study, we investigated CYP19 gene expression and its regulation in endometrial tumor samples (n = 9). Using a specific method of competitive polymerase chain reaction after reverse transcription, varying levels of P450arom transcripts were detected in all endometrial adenocarcinomas (n = 8) and one mixed Mullerian tumor studied. No correlations were observed between P450arom transcript levels and histological type of the tumor, grade, myometrial invasion, stage of the disease, or patient age. We have recently demonstrated that the tissue-specific regulation of CYP19 gene transcription is in part the consequence of alternative promoter use. The use of each promoter gives rise to a P450arom transcript with a unique untranslated 5'-end. We analyzed the untranslated first exons in 5'-terminals of P450arom transcripts in endometrial adenocarcinomas using a specific reverse transcription-polymerase chain reaction/Southern hybridization method we recently developed. Our findings indicated the gonadal-type (promoter II) and one of the adipose stromal cell-type (I.3) promoters were primarily used for P450arom expression in adenocarcinomas. On the other hand, distribution of transcripts specific for I.3, I.4 (another adipose-type promoter), and promoter II in one mixed Mullerian tumor was uniform. Placental promoter (I.1)-specific P450arom transcripts were not detected in endometrial tumors. As P450arom transcripts were detected in all endometrial malignancies studied, whereas they were not demonstrable in the disease-free endometrium, activation or failure of inhibition of aromatase expression in these tumors may serve to promote neoplastic proliferation. PMID- 7989491 TI - Down-regulation of G alpha s in human myometrium in term and preterm labor: a mechanism for parturition. AB - We have previously reported that G alpha s is expressed at considerably higher levels in myometrium taken from pregnant than from nonpregnant women. In the present study we have determined adenylyl cyclase activity in myometrial membranes by measuring the conversion of [alpha-32P]ATP to [32P]cAMP and have measured guanosine triphosphate-binding protein expression by immunoblotting with specific antibodies. Here we report that the increase in G alpha s expression in pregnant myometrium is associated with a significant increase in G alpha s coupled adenylyl cyclase activity, as estimated by incubating myometrial membranes in the presence of 5'-guanylyl-imidodiphosphate with and without prostaglandin E2. Moreover, in myometrium from women in spontaneous labor G alpha s levels and G alpha s-coupled adenylyl cyclase activity are reduced to the levels observed in nonpregnant tissue. There was no apparent change in forskolin stimulated adenylyl cyclase activity in nonpregnant, pregnant, and laboring tissue. The increase in G alpha s expression in pregnant myometrium may facilitate agonist-induced cAMP formation, resulting in prolonged relaxation of the uterus during gestation. Down-regulation of G alpha s would decrease the relaxing effect exerted by cAMP and may be a triggering mechanism for the initiation of labor. PMID- 7989492 TI - A 3-basepair in-frame deletion (delta Leu999) in exon 17 of the insulin receptor gene in a family with insulin resistance. AB - We studied a woman with acanthosis nigricans and insulin resistance. The patient's Epstein-Barr virus-transformed lymphocytes revealed slightly decreased insulin binding and markedly decreased insulin-stimulated autophosphorylation of the insulin receptor. The nucleotide sequence analysis of the patient's genomic DNA revealed a 3-basepair in-frame deletion in one allele, resulting in the loss of leucine at position 999 of the insulin receptor (delta Leu999). The messenger ribonucleic acid transcripts from the mutant allele in the patient's lymphocytes were not decreased. Insulin-stimulated autophosphorylation of the insulin receptor from cells expressing delta Leu999 mutant insulin receptor complementary DNA was markedly decreased. The proband, her mother, elder brother, and younger brother, who were heterozygous for this mutation, showed moderate or marked hyperinsulinemia during oral glucose tolerance tests. Although fasting glucose levels were normal and fasting insulin values were preserved in all subjects with the mutation for the 8-yr period of observation, a tendency of progressive increase in postload glucose levels was observed. These results suggest that the delta Leu999 mutation, which reduces tyrosine kinase activity, was responsible for insulin resistance and contributed to postload hyperglycemia. PMID- 7989493 TI - [111In-DTPA-D-Phe1] octreotide scintigraphy in thyroidal and orbital Graves' disease: a parameter for disease activity? AB - Visualization of malignant lymphomas and granulomatous disease is possible by [111In-DTPA-D-Phe1]octreotide scintigraphy through binding of the radioligand to somatostatin receptors on activated leukocytes. Because thyroidal and orbital tissues are infiltrated by activated leukocytes in Graves' disease, a cross sectional study to visualize disease activity with [111In-DTPA-D-Phe1]octreotide scintigraphy was performed. A correlation between thyroidal [111In-DTPA-D Phe1]octreotide accumulation and free T4 (disease expression) and thyroid binding inhibiting immunoglobulins (disease activity) is present in untreated hyperthyroid Graves' disease. There is also a correlation between orbital [111In DTPA-D-Phe1]octreotide uptake and the clinical activity score (disease activity) and total eye score (disease expression), respectively, in Graves' orbitopathy. Visualization of thyroidal and orbital Graves' disease is feasible, but further investigation is necessary to establish the role of [111In-DTPA-D-Phe1]octreotide scintigraphy in representing disease activity and expression and in predicting therapeutical outcome. PMID- 7989494 TI - Angiotensin-II mediates norepinephrine and neuropeptide-Y secretion in a human pheochromocytoma. AB - The potential role of angiotensin-II in mediating catecholamine and neuropeptide Y release in a human pheochromocytoma has been investigated. Angiotensin-II type I receptors are transcribed and translated into functional proteins in a surgically removed pheochromocytoma. Primary cell culture of the tumor has been studied in a perfused system. Angiotensin-II increased the release of norepinephrine and neuropeptide-Y by the pheochromocytes. Activation of the angiotensin-II type I receptors by angiotensin-II was associated with a rise in cytosolic free calcium. The renin-angiotensin system may, therefore, contribute to the secretion of catecholamines and NPY occurring in patients with pheochromocytoma and when stimulated trigger hypertensive crisis. PMID- 7989495 TI - Expression of interleukin-1 receptor antagonist in human pituitary adenomas in vitro. AB - The production of cytokines and their receptors in the pituitary gland as well as receptor-mediated cytokine effects on pituitary function have been demonstrated. We have investigated whether the naturally occurring interleukin-1 receptor antagonist (IL-1ra), which has been shown to block IL-1 biological actions during inflammatory processes, could be expressed in human pituitary adenomas (n = 16) cultured in vitro. By polymerase chain reaction of reverse-transcribed RNA we detected IL-1ra messenger RNA in cultures of all types of pituitary adenomas under basal conditions as well as after stimulation of the cells with endotoxin or phorbol myristate acetate. The amplified complementary DNA fragment was identical to the fragment observed when RNA from purified human monocytes was subjected to reverse transcription polymerase chain reaction. In addition, we provide evidence that the IL-1ra messenger RNA detected in human pituitary adenomas corresponds to the intracellular IL-1ra variant. By using specific primers for the monocyte/macrophage marker CD14 as a control, we could exclude a contamination by monocytes or macrophages in the cell cultures of pituitary adenomas as a source of IL-1ra expression. Immunofluorescence studies showed the presence of cellular IL-1ra protein in the pituitary adenoma cultures and the colocalization with hormone-producing cells in GH- and ACTH-secreting adenomas. Production of IL-1ra within the anterior pituitary may act as a protective mechanism, modulating the sensitivity of pituitary cells to circulating or intrinsically produced IL-1 during inflammatory or tumoral processes. PMID- 7989496 TI - Comment: effect of cytokines on prolactin production by human decidual stromal cells in culture: studies using cells freed of bone marrow-derived contaminants. AB - Human decidua contains resident decidual cells alongside a population of bone marrow-derived cells, among which macrophages and large granular lymphocytes are most abundant. We hypothesized that soluble effectors produced by bone marrow derived cells may modulate the function of the decidual cells. To investigate this, a cell purification protocol was devised that involved digestion of first trimester decidua with collagenase and hyaluronidase to produce a mixed stromal cell suspension from which the bone marrow-derived cells were removed using immunomagnetic beads coated with anti-CD45. The resulting stromal cells were maintained in culture in the presence of progesterone and were found to produce PRL. The effect of a panel of cytokines on PRL production was examined. Tumor necrosis factors-alpha and -beta had a dose-dependent inhibitory effect, and tumor necrosis factor receptors were identified on the cells. Interleukin 1 alpha and 1 beta, platelet-derived growth factor, and transforming growth factor-beta 1 were also found to inhibit PRL production, and platelet-derived growth factor and transforming growth factor-beta 1 stimulated cell proliferation. These findings suggest an interaction between the immune and endocrine systems in regulating the maternal environment of early pregnancy. PMID- 7989497 TI - Perivascular location of a chemokine interleukin-8 in human endometrium: a preliminary report. AB - The cytokine interleukin-8 (IL-8) is capable of inducing selective neutrophil chemotaxis and activation and has been postulated as the signal for neutrophil recruitment and activation in reproductive tissues. The aim of this study was to examine the localization of IL-8 in non-pregnant human endometrium in view of its potential as a local modulator of endometrial function. Endometrial biopsies (proliferative, n = 8; secretory, n = 7) from 15 subjects were available for immunolocalization of IL-8. Primary antibody (rabbit polyclonal against IL-8) application was followed by either a horseradish peroxidase streptavidin detection system (proliferative, n = 5; secretory, n = 4) or an avidin-biotin alkaline phosphatase detection method (proliferative, n = 3; secretory, n = 3). All endometrial biopsies showed heterogeneous positive staining for IL-8 in association with blood vessels in both proliferative and secretory phase biopsies. The immunostaining was apparently not associated with endothelial cells but rather appeared to be associated with the smooth muscle layer of arterioles. Secretory phase biopsies exhibited immunoreactivity in association with small blood vessels and spiral arterioles. The perivascular location of IL-8 throughout the stages of the human menstrual cycle is consistent with its proposed biological role as a modulator of endometrial function, especially synergism with prostaglandin E and the transmigration of leukocytes. PMID- 7989498 TI - Cellular retinoid binding proteins and nuclear retinoic acid receptors in endometrial epithelial cells. AB - Retinoic acid, one of the most potent of the naturally occurring retinoids (retinol and derivatives), is required in vivo for the maintenance of epithelial cell growth. This study describes the pattern of expression of nuclear retinoic acid receptors (RARs and RXRs), and cellular binding proteins for retinol and retinoic acid (CRBP I, CRABP I and II), in endometrial epithelial cells. The effects of retinoic acid on the expression of these receptors in endometrial epithelial cells have also been studied and compared with its effects in endometrial stromal cells. Messenger RNA for RAR-alpha, RAR-beta, RAR-gamma, RXR alpha, CRBP I and CRABP II was detected by Northern blotting of total RNA extracted from cultured epithelial cells. In comparison with stromal cell RNA that was used as an internal standard, CRBP I appeared to be more abundant in epithelial cells, whereas CRABP II appeared to be more abundant in the stromal cells. This implies that the intracellular concentration of retinoic acid may be maintained at higher levels in epithelial cells compared to stromal cells. In addition, the response of the two cell types to retinoic acid differs: RAR-beta is induced in stromal cells treated with all-trans retinoic acid but not in epithelial cells. From these data we suggest that retinoid physiology differs between endometrial epithelial and stromal cells. Furthermore, by analogy with other studies, we propose that retinoic acid may be maintained at a higher intracellular concentration in endometrial epithelial cells to facilitate differentiation to a glandular phenotype.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7989499 TI - Ovarian cyst formation in two pre-menopausal patients treated with tamoxifen for breast cancer. AB - Pre-menopausal tamoxifen treatment causes hyperoestrogen production and ovarian cyst formation. Two pre-menopausal breast cancer patients who were treated with tamoxifen developed both permanent supraphysiological oestrogen concentration and ovarian cysts. Serum oestrogen decreased to post-menopausal concentrations and ovarian cysts completely resolved during and following simultaneous treatment with tamoxifen and gonadotrophin-releasing hormone agonist (GnRHa). In pre menopausal breast cancer patients, GnRHa may prevent possible side-effects of tamoxifen, such as ovarian cysts and supraphysiological oestrogen production. PMID- 7989500 TI - Simplification of IVF: minimal monitoring and the use of subcutaneous highly purified FSH administration for ovulation induction. AB - During the past few years much effort has been put into simplifying the clinical management of in-vitro fertilization/embryo transfer cycles. One important step was the introduction of transvaginal ultrasound-guided oocyte collection, as previously described. This study describes further simplifications of the clinical management of ovarian stimulation. During the period 1st January 1991 to 31st August 1993, three major simplification steps were introduced. All cycles were down-regulated with a gonadotrophin-releasing hormone (GnRH) agonist according to a long protocol permitting fairly precise programming of the oocyte collection. During period I (n = 329 cycles), closer monitoring by several pelvic ultrasound scans and serum oestradiol was used for monitoring the ovarian stimulation. During period II (n = 230 cycles), only one ultrasound scan was used for monitoring the ovarian cycle; oocyte collections during weekends were avoided. During period III (n = 386 cycles), further simplification of the clinical management was introduced by using a highly purified follicle stimulating hormone (FSH) (Fertinorm/Metrodin HP), which was self-administered s.c. for ovarian stimulation. The take-home baby rates per started cycle for periods I, II and III were 16.4, 32.6 and 31.3% respectively. These figures indicate that when using long down-regulation with a GnRH agonist, simplification of the monitoring of the ovarian stimulation is possible without decreasing the pregnancy rate. Furthermore, the use of a highly purified FSH, self-administered s.c., greatly simplified treatment without compromising cycle outcome or increasing the risk of developing an ovarian hyperstimulation syndrome. PMID- 7989501 TI - Modulation of the action of gonadotrophin surge-attenuating factor by gonadotrophin-releasing hormone. AB - Gonadotrophin surge-attenuating factor (GnSAF) is a putative non-steroidal ovarian factor which attenuates the luteinizing hormone (LH) surge in superovulated women through the reduction of the pituitary response to gonadotrophin-releasing hormone (GnRH). The mechanism of action of GnSAF on gonadotrophin secretion was further studied by investigating six normally ovulating women in two cycles--a spontaneous and a follicle-stimulating hormone (FSH)-treated cycle. The response of the pituitary to five consecutive pulses of GnRH was investigated in late follicular phase (follicle size 15 mm) of both cycles. GnRH pulses, 10 micrograms each, were injected i.v. every 2 h and LH was measured in blood samples taken before and 30, 60 and 120 min after each pulse. FSH was injected daily at the fixed dose of 225 IU starting on cycle day 2. Peak values of LH increment occurred 30 min after each pulse. However, maximal LH increment occurred in both cycles after the second GnRH dose. In the FSH cycles the response of LH to the first three pulses was significantly attenuated compared with the spontaneous cycles, while the response to the fourth and fifth pulses was similar in the two cycles. In both cycles, LH increment 30 min post GnRH (net increase above the previous value) was similar after the fourth and fifth pulses. Serum concentrations of oestradiol and immunoreactive inhibin, although higher in the FSH cycles, remained stable throughout the GnRH experimental period in both cycles. These results demonstrate that multiple submaximal doses of GnRH can override the attenuating effect of GnSAF on LH secretion.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7989502 TI - Effect of the antiprogestin onapristone on follicular growth in women. AB - The effects of the antiprogestin onapristone on the menstrual cycle were assessed in surgically sterilized volunteer women. The steroid was given orally at the dose of 5, 15 or 50 mg/day, from day 5 to day 11 of the cycle. Ovarian ultrasonography and hormonal determinations in plasma and urine were used to monitor the pre-treatment, treated and post-treatment cycles. Onapristone, given at a dose of 5 mg/day, affected follicular growth inconsistently. The dose of 15 or 50 mg/day arrested follicular growth and oestradiol increase and delayed gonadotrophin surge, extending the length of the follicular phase in five of seven women in each group. After discontinuation of treatment the leading follicle resumed its growth and ovulation occurred as judged by the elevation of plasma progesterone, preceded in most but not all cases by an echographic image of follicular collapse. The ensuing luteal phases were not significantly altered in length or plasma progesterone concentration. Cortisol concentrations were unaffected and no serious side-effects were recorded. The antifolliculotrophic effect of onapristone demonstrated here, together with previous reports of similar activity of mifepristone in women, indicate that this may be a general property of compounds that interfere with progesterone receptor function. PMID- 7989503 TI - Somatostatin in human follicular fluid. AB - To demonstrate the presence of somatostatin in human pre-ovulatory follicular fluid, and to assess the role of this peptide in follicular maturation, a total of 66 follicular fluid samples were obtained from 26 patients at the time of oocyte recovery for in-vitro fertilization. Follicular fluid concentrations of somatostatin, oestradiol, progesterone and androstenedione were measured by immunoassay. Somatostatin concentrations in concomitantly obtained plasma samples were also analysed. Follicular fluid somatostatin concentrations ranged from undetectable (< 1.5 pmol/l) to 109.4 pmol/l. The mean +/- SE somatostatin concentrations in follicular fluid (12.8 +/- 1.8 pmol/l) were significantly (P < 0.0001) increased compared to corresponding plasma concentrations of somatostatin (6.5 +/- 0.2 pmol/l). A significant and positive correlation existed between follicular fluid and plasma somatostatin concentrations (r = 0.27; P < 0.03). No differences in either follicular fluid or plasma somatostatin concentrations were found between different stimulation protocols or diagnostic groups. Neither did follicular fluid somatostatin concentration vary with follicular size. Similarly, no differences in somatostatin concentrations were found between follicular fluids associated with fertilized (13.2 +/- 2.1 pmol/l) or non-fertilized oocytes (10.5 +/- 1.6 pmol/l). Follicular fluid concentrations of somatostatin correlated positively with those of progesterone (r = 0.30; P = < 0.04), but not with those of oestradiol or androstenedione or with the androstenedione/oestradiol ratio. The relationship between follicular fluid somatostatin and progesterone concentrations suggests that follicular fluid somatostatin may have a physiological role in follicular maturation and the luteinization process. PMID- 7989504 TI - AJ-FS1 monoclonal antibody detects a novel group of non-glycosylated antigens within the human sperm tail fibrous sheath. AB - AJ-FS1 is one of a new series of monoclonal antibodies (MoAbs) raised by immunizing mice with isolated human sperm tail fibrous sheath. Using indirect immunofluorescence (IIF), the AJ-FS1 MoAb did not react with the surface antigens of viable sperm, but did stain the flagellar principal piece of sperm dried onto slides or those demembranated with 1% Triton X-100. The specificity of the antibody for the fibrous sheath was confirmed by immunogold electron microscopy which showed the distribution of gold particles on the outer fibrous sheath surface, and its reaction with the Western blots of purified fibrous sheath preparations where multiple protein bands with mol. wt ranging between 97 and 28 kDa were identified. The same peptides were also detected in urea-dithiothreitol (DTT) fraction of sequentially extracted spermatozoa but not in Triton or Triton- DTT sperm lysates. The failure of sodium metaperiodate to abrogate the antibody reaction in both Western blotting and IIF indicated the non-glycosylated nature of the antigens. IIF screening of human testicular cryostat sections with AJ-FS1 MoAb showed its reactivity with the assembled fibrous sheath of maturing sperm tails only; thus indicating the late appearance of the antigens during spermatogenesis. The antibody did not react with skin, oesophagus, tongue, liver, kidney, placenta, uterus, cervix or their blood vessels. The significance of these results is discussed together with the importance of AJ-FS1 MoAb as a specific probe for the characterization of the fibrous sheath antigens in both normal and abnormal flagella. PMID- 7989505 TI - Refinements in the methodology of injection for transvaginal gamete intra fallopian transfer. AB - Eighty-seven volunteer patients with non-tubal infertility initially intending to undergo gamete intra-Fallopian tube transfer (GIFT) via a transabdominal route were re-scheduled for ultrasound-guided transvaginal GIFT which was performed using a Jansen-Anderson tubal transfer set. Emphasis was placed on (i) definite ultrasound confirmation of the transfer catheter within the Fallopian tube, (ii) low transfer volumes (50 microliters), (iii) high sperm transfer densities and (iv) slow injection of gametes. Transvaginal Fallopian tube catheterization was possible in 83 patients (95.4%). Twenty-three of 83 (27.7%) patients conceived (clinical pregnancy). The viable ongoing pregnancy rate was 20.5%. These results compare favourably to those previously reported for both transvaginal and transabdominal GIFT. This study suggested that the fluid dynamics of gamete injection following transvaginal Fallopian tube catheterization are different to those following transabdominal methods. Further study is necessary to define the optimal methodology for transvaginal GIFT and to enhance the ability of the procedure to produce pregnancy rates comparable to transabdominal GIFT. PMID- 7989506 TI - Multiple follicular development associated with herbal medicine. AB - After three endocrinologically normal cycles while undergoing unstimulated in vitro fertilization treatment, a woman took a herbal medicine (Vitex agnus castus) at the beginning of a fourth unstimulated IVF treatment cycle. In this fourth cycle, her serum gonadotrophin and ovarian hormone measurements were disordered. One embryo resulted from the three eggs collected but a pregnancy did not ensue. She had symptoms suggestive of mild ovarian hyperstimulation syndrome in the luteal phase. Two subsequent cycles were endocrinologically normal. We do not advocate the use of this herbal medicine to promote normal ovarian function. PMID- 7989507 TI - The CpG island of the FMR-1 gene is methylated differently among embryonic tissues: implication for prenatal diagnosis. AB - We studied the methylation status of the CpG island of the FMR-1 (fragile X syndrome) gene to recognize the possibility of its prenatal diagnosis with early pregnant subjects. Southern hybridization using EcoRI/BssHII restriction enzymes double digestion was performed in the brain and chorionic villi of 8th week embryos, and the placenta and cord blood of newborns. No methylation of the FMR-1 gene occurred in both of the tissues examined in males, while 50% of the cells in females were methylated in both the brain and the cord blood, indicating that methylation occurs with inactivation of the X-chromosome in accordance with the literature. However, there was no methylation in either the chorionic villi or placenta in female as well as in males. Some extra-embryonic tissues such as the chorionic villi and the placenta escape X-chromosome FMR-1 gene inactivation and it can be the exception in the lyonization. To assess the methylation status in prenatal diagnosis, precautions are needed and they are not suitable for prenatal diagnosis. PMID- 7989508 TI - Sperm motility and kinetics of dynein ATPase in astheno- and normozoospermic samples after stimulation with adenosine and its analogues. AB - We tested the effects of adenosine and 2-deoxyadenosine on the activation of human spermatozoa. In the asthenozoospermic group of patients adenosine produces an increase in sperm motility from 33.3 +/- 2.1% to 42.1 +/- 3.4%, progressive motility from 22.5 +/- 1.3% to 28.6 +/- 1.7% and forward progression rating from 2.1 +/- 0.2% to 2.8 +/- 0.1%. 2-Deoxyadenosine stimulated asthenozoospermic samples to a greater degree than adenosine. Sperm motility rose to 48.9 +/- 3.4%, progressive motility to 32.1 +/- 3.4% and forward progression rating to 3.0 +/- 0.1% following stimulation with 2-deoxy-adenosine. The kinetic parameters and basic characteristics of dynein ATPase were determined. The maximum activity of dynein ATPase, Vmax, was significantly different (P < 0.001) for asthenozoospermic and normozoospermic samples: 6.46 +/- 2.1 nmol Pi/mg/min and 16.99 +/- 3.7 nmol Pi/mg/min respectively. However, the enzyme affinity for ATP was not different. Stimulation of asthenozoospermic samples with adenosine and 2 deoxyadenosine caused an increase of Vmax (70-90% and 90-110% respectively) and no significant change in KM was observed. In order to block the nucleoside transporter and to eliminate the action of adenosine inside the cell, dipyridamole was used but the effects of adenosine were not neutralized. 5'-(N ethylcarboxy-amido)-adenosine showed effects similar to those of adenosine, even when applied in 1 microM concentration. These results indicate that adenosine and its analogues stimulate sperm motility and activity of dynein ATPase, most probably via A2 receptors. PMID- 7989509 TI - Teratozoospermia and in-vitro fertilization: a randomized prospective study. AB - A prospective randomized study was conducted to assess the prognostic value of sperm morphology in an in-vitro fertilization (IVF) programme, using strict criteria. The first group (T, teratozoospermic) included 32 couples with an isolated teratozoospermia in the male partner (morphology < 9% normal). The second group (C, control) contained 36 couples with normal semen parameters, including morphology (> 9% normal, strict criteria). In both groups, 50 IVF cycles were performed. Patients were matched for indication for IVF. There was no difference between the two groups regarding age, duration of infertility, stimulation protocol, catheter used for embryo transfer and different sperm parameters. A statistically significant difference between the T and C groups respectively was observed regarding the fertilization rate (69.2 and 79.4%, P < 0.05), pregnancy rate per cycle (12.0 and 42%, P < 0.001), the pregnancy rate per transfer (13.9 and 42.0%, P < 0.01) and per embryo transferred (6.1 and 14.8%, P < 0.05). No pregnancy occurred in the poor prognosis group (morphology < 5% normal). In cases of moderate teratozoospermia, the fertilization rate appeared normal (78.6%) but the conception rate remained low. We concluded that the use of strict criteria in the assessment of sperm morphology is useful in predicting fertilization and pregnancy rate in the human in-vitro model. PMID- 7989510 TI - Enhanced recruitment of motile spermatozoa by prostasome inclusion in swim-up medium. AB - Prostasomes, which are prostate-derived organelles, were purified from human seminal plasma for inclusion in Earle's balanced salt solution (EBSS) medium with or without human serum albumin. These media were used for swim-up experiments and the subsequent analyses of sperm motility parameters at different incubation times. The yield of motile spermatozoa after swim-up in EBSS medium enriched with boiled prostasomes was increased by 32% compared with EBSS containing albumin. Native prostasomes were less active. Combinations of albumin and either prostasomes or boiled prostasomes significantly increased the recovery of motile spermatozoa and also increased the percentage of spermatozoa displaying progressive motility after 1 h of incubation. Media lacking albumin showed lower values regarding progressive motility after 22 h of incubation. A beneficial effect of prostasomes was noted on lateral head displacement and percentage of hyperactive spermatozoa during the first 6 h of incubation. These results suggest that inclusion of prostasomes, especially boiled prostasomes, in swim-up media may improve the recovery of hyperactive motile spermatozoa for up to 6 h in cases of established male factor infertility, and consequently increase the opportunities for fertilization. PMID- 7989511 TI - The use of anticlusterin monoclonal antibodies for the combined assessment of human sperm morphology and acrosome integrity. AB - Clusterin is an abundant protein in the human male reproductive tract which appears to be produced by the testis, epididymis and the seminal vesicles. Using monoclonal antibodies and an amplified immunoperoxidase technique, we have identified two apparently biochemically distinct forms of clusterin on human spermatozoa. Morphologically abnormal spermatozoa have an extensive surface coating of conventional 80 kDa native clusterin, but this form of clusterin is not detectable on normal spermatozoa. Normal spermatozoa, however, contain within the acrosomal cap a different form of clusterin, reactive with an anticlusterin alpha-chain antibody. Agglutinated spermatozoa, most of which are grossly abnormal, were intensely labelled with the antibody against conventional 80 kDa clusterin, suggesting that the 'clustering' properties of this protein may play a role in the aggregation of abnormal spermatozoa. Anticlusterin monoclonal antibodies may be useful for semen analysis. Staining spermatozoa with anticlusterin monoclonal antibodies is a technically simple method which provides a visually obvious means of assessing spermatozoa morphology and acrosome status simultaneously. The current data also suggest that different functions of clusterin in the reproductive tract may be attributed to different molecular forms of the protein. PMID- 7989513 TI - Preliminary characterization of a factor in human follicular fluid that stimulates human spermatozoa motion. AB - Follicular fluid alters the physiology and behaviour of spermatozoa by increasing acrosome reaction, accelerating capacitation, attracting the spermatozoon and enhancing vigorous motion of the cell. The objective of this study was to characterize the factor(s) in human follicular fluid that causes vigorous spermatozoa motion. Follicular fluid and its fractions were tested for stimulation of spermatozoa motion using a standardized assay which employs a computerized digital imaging system. Our results show that both follicular fluid and its methanol extract stimulate vigorous spermatozoa motion. To determine the characteristics of the active factor(s), the methanol extract was subjected to molecular weight fractionation, protease digestion, microcrystalline thin-layer chromatography (TLC) and C18 reverse-phase high-pressure liquid chromatography (HPLC). The spermatozoa motion stimulator in the methanol extract was dialysable against a low molecular weight membrane (1000 Da), insensitive to boiling and low pH (3.5) and was largely inactivated by proteinase K digestion. The activity was detected near the solvent front on TLC. Using reverse-phase HPLC monitored at 254 nm (UV), the activity eluted as a single peak of activity at low methanol concentration, indicating that the activity was relatively hydrophilic. The activity in the HPLC peak lost most of its motion-stimulating ability after digestion with proteinase K. The motion stimulator could be a peptide analogous to the egg-associated peptides characterized in echinoderms which stimulate spermatozoa motion, respiration and chemotaxis. PMID- 7989512 TI - Purification and characterization of a sperm-binding glycoprotein from human endometrium. AB - A sialic-acid-binding protein (SABP) was purified to apparent homogeneity from human endometrial scrapings taken at various stages of the menstrual cycle from normal cycling females. The 54 kDa monomer was found to be an O-linked glycoprotein with a total carbohydrate content of 34%. This protein agglutinated washed 2% v/v rabbit red blood cells (RBC) in the presence of calcium. Amongst sialic acids and sialoglycoproteins tested for haemagglutination inhibitory activities, N-glycolyl neuraminic acids and human alpha 1-acid glycoprotein were found to be the most potent, the agglutination activity being totally abolished on desialylation of the RBC in the presence of neuraminidase. Western blot studies showed it to be present in the uterine fluid but absent in normal female serum and in full-term placenta. It was also absent in endometrial homogenates of some cases of unexplained primary infertility. Specific binding studies and Scatchard analysis revealed that 125I-labelled human SABP ligand can bind to human spermatozoa with a Ka = 2.6 x 10(9) M-1, their receptors probably being glycoconjugates having a terminal sialic acid moiety, since the sperm-protein interaction could also be abolished when spermatozoa were desialylated with neuraminidase. The binding occurred specifically on the sperm head plasma membrane and decreased markedly when spermatozoa were previously capacitated in vitro using human serum albumin, implicating the possible loss of a sialoglycoprotein receptor to which the ligand binds during capacitation. The biological importance of this sperm-binding secretory glycoprotein and its functional significance in human reproduction have been discussed. PMID- 7989514 TI - Sperm chromosome complements in a man heterozygous for a reciprocal translocation t(2;3)(q24;p26). AB - Sperm chromosome complements were studied in a man heterozygous for a reciprocal translocation t(2;3)(q24;p26). This man was identified during a family study after his sister was investigated for amenorrhea. A total of 92 spermatozoa were karyotyped after in-vitro penetration of hamster eggs. The frequencies of alternate, adjacent 1, adjacent 2 and 3:1 segregations were 55.4, 36.1, 7.2 and 1.2% respectively. For alternate segregations, the number of normal spermatozoa (n = 25) was not significantly different from the number of spermatozoa carrying a balanced form of the translocation (n = 21), as theoretically expected. The proportion of spermatozoa with an unbalanced form of the translocation was 44.6%. There was no evidence for an interchromosomal effect since the frequencies of numerical and structural abnormalities (unrelated to the translocation) were within the normal range of control donors. PMID- 7989515 TI - Comparison of ampullary assessment by falloposcopy and salpingoscopy. AB - The purpose of this study was to compare and contrast falloposcopic and salpingoscopic ampullary assessments in a series of 20 women undergoing tubal microsurgery for distal tubal or peritubal disease. Four women had an extrinsic cause for their peritubal adhesions, and would have been expected to exhibit a normal oviductal canal. All of the falloposcopic examinations were performed as an outpatient procedure. Salpingoscopic examinations were undertaken at the time of microsurgery. The endoscopic examinations were undertaken by two clinicians, who were blinded to each other's assessments and to the indication for surgery. Of the 31 Fallopian tubes which were examined, 24 were found to be abnormal by salpingoscopy and 23 were found to be abnormal by falloposcopy. Total score and scores for epithelial appearance, vascularity, intraluminal adhesions and dilatation were found to be significantly associated. Furthermore, falloposcopy predicted salpingoscopic status correctly in 84% of cases. These data suggest that falloposcopy is a useful method of assessing ampullary condition. PMID- 7989516 TI - Resection of large uterine septum during early pregnancy and at the oocyte retrieval--peculiarities of two cases. AB - Two cases of hysteroscopic metroplasties for large septate, one performed at the time of oocyte retrieval, and the second at the time of curettage for early first trimester spontaneous pregnancy loss, are reported. The peculiarities of medical circumstances and surgical approaches are discussed. Each patient had an excellent post-surgical result and a successful pregnancy. The notion that the performance of hysteroscopic surgery in women presenting with supraphysiological serum oestradiol concentrations or an early miscarriage would increase intra operative bleeding and post-operative complications respectively is challenged by this report. The authors emphasize that thorough counselling, meticulous planning, appropriate follicular phase timing and excellent surgical techniques remain the mainstay for success. PMID- 7989517 TI - Lack of evidence for the production of interferon-alpha-like species by the cultured human pre-embryo. AB - The aim of this study was to determine if the human pre-embryo produces a substance similar to the trophoblast interferon secreted by ruminant trophoblasts. Human embryos surplus to in-vitro fertilization (IVF) treatment were cultured up to 14 days following IVF. Viable cultures were determined by microscopic examination and by assay of the culture medium for human chorionic gonadotrophin (HCG). Four stages of development were visually identified: pre blastocyst, unhatched, part-hatched and fully hatched blastocyst. HCG was detected in medium which had contained the more developmentally advanced embryos. A total of 62 samples were assayed for human interferon-alpha (IFN-alpha), including all cultures presumed viable. None contained detectable IFN-alpha immunoreactivity. Out of 14 candidate samples subjected to cytopathic effect reduction assay, none contained antiviral activity. We suggest that a trophoblast derived interferon, unlike HCG, does not play a significant role in the maternal recognition of pregnancy in humans. PMID- 7989518 TI - Assisted hatching with or without bovine oviductal epithelial cell co-culture for poor prognosis in-vitro fertilization patients. AB - Older patients and those who consistently return for embryo transfer but without implantation were studied to see if a combination of day 3 assisted hatching and co-culture (AH+CC) might be beneficial compared to assisted hatching alone (AH alone). Female patients of > or = 38 years and couples who had previously failed to implant embryos three times or more were prospectively and randomly assigned to either an experimental or a control group. In the experimental group all embryos were co-cultured on partial monolayers of bovine oviductal epithelial cells for 2 days followed by assisted hatching by zona drilling (AH+CC). All control embryos were cultured by standard procedures until day 3 when they also underwent zona drilling prior to uterine transfer (AH-alone). With 50 cycles in each group there was unfortunately a marginal bias against the AH+CC group in that these patients had undergone a higher number of previous transfer cycles. There was a marginally lower percentage of fragmentation and a significantly higher degree of zona thickness variability in the AH+CC embryo group. Embryonic implantation was significantly increased (P < 0.05) in the AH+CC group (18%) when compared to the AH-alone group (10%). This difference was reflected in a significantly higher (P < 0.05) initial pregnancy rate (52 versus 32%) in the AH+CC group, and a higher (not significant) viable pregnancy rate (38 versus 22%). PMID- 7989519 TI - Use of a polymorphic dinucleotide repeat sequence to detect non-blastomeric contamination of the polymerase chain reaction in biopsy samples for preimplantation diagnosis. AB - Using the polymerase chain reaction (PCR), amplification of two different target DNA sequences has been achieved with high frequency using single human blastomeres as template for the duplex reaction. One sequence is located within the beta-globin gene and contains the sickle cell locus, the other is a polymorphic dinucleotide repeat, which, as well as acting as a positive control for amplification, was used to check the origin of the amplified DNA. A comparison of the sequences amplified from the blastomere with sequences amplified from parental samples confirmed that amplification of blastomeric sequences, but not extraneous contaminating DNA, had taken place in most cases. The efficacy of this system for detecting extraneous DNA was checked by deliberately contaminating single blastomeres with foreign cells. The presence of contamination was detected by the amplification of sequences not present in blastomeric DNA and which therefore must have been amplified from extraneous contaminating DNA. PMID- 7989520 TI - No evidence for the expression of the progesterone receptor on peripheral blood lymphocytes during pregnancy. AB - The expression of the progesterone receptor in human peripheral blood lymphocytes was analysed, using an enzyme linked immunosorbent assay (Abbott PgR-EIA monoclonal), in order to evaluate its prognostic character in the context of spontaneous abortion. Cytosols were prepared from lymphocytes of 24 healthy pregnant women (11 first, 10 second and three third trimester), seven healthy non pregnant women, nine women with recurrent spontaneous abortion, and six healthy men. In addition, a human breast carcinoma cell line (ZR-75-1), which expresses the progesterone receptor, was analysed throughout. The ZR-75-1 cell line showed an expression of 642 fmol/mg whereas lymphocytes of pregnant women showed an expression < or = 4 fmol/mg. Lymphocytes of non-pregnant women, women with threatened pre-term delivery, and men showed equivalent levels: 3 +/- 1, 3 +/- 2 and 5 +/- 4 fmol/mg respectively. These results show that there is no evidence of specific expression of the progesterone receptor in pregnancy and exclude any prognostic character in spontaneous abortion. A role for the progesterone receptor in the mechanism of the known effect of progesterone on peripheral blood lymphocytes is also excluded. PMID- 7989521 TI - Human menopausal gonadotrophin increases pregnancy rate in comparison with clomiphene citrate during replacement cycles of frozen/thawed pronucleate ova. AB - In a prospective randomized study, the effect of two ovulation induction regimens on implantation rate of frozen/thawed pronucleate ova was investigated. Patients received either human menopausal gonadotrophin (HMG) or clomiphene/HMG. Ovulation induction was done on an individual basis using ultrasound and plasma 17 beta oestradiol concentrations. Ovulation was induced with human chorionic gonadotrophin (HCG) when the leading follicle reached a diameter of 18 mm. Pronucleate ova had been frozen using the slow-freezing method of Lassalle et al. (1985) (Fertil. Steril., 44, 645-651) and were thawed in synchrony with the age of the endometrium. Both groups of patients were comparable for age, indication for in-vitro fertilization, pre-ovulatory 17 beta-oestradiol concentration, number of large follicles and number and quality of embryos transferred. The only difference found was that HCG was administered 1 day earlier in the HMG group compared to the clomiphene/HMG group (P < 0.01). Using univariate analysis, the pregnancy rate was higher in patients stimulated with HMG alone compared to those stimulated with clomiphene/HMG (27 versus 15% respectively; P < 0.03), when HCG was administered later in the menstrual cycle (P < 0.01) and when more and better quality embryos were transferred (P < 0.01). Using multivariate regression analysis, the influence of the stimulation on pregnancy rate was even more pronounced (P < 0.01) when the day of HCG administration and the number and quality embryos transferred were taken into account. Therefore, we conclude that HMG alone increases pregnancy rate compared to clomiphene/HMG during replacement cycles of frozen/thawed pronucleate ova. These data suggest that HMG results in a better endometrium receptivity for embryos.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7989522 TI - Relaxin concentrations in exoembryonic fluids during the first trimester. AB - In 15 women undergoing therapeutic termination of pregnancy (8-13 weeks), the median concentration of relaxin was 1000 ng/l in maternal serum, 122 ng/l in coelomic fluid and 9 ng/l in amniotic fluid. Its presence in coelomic fluid suggests that relaxin may be present in the fetal circulation and thus be able to influence embryonic development during the period of organogenesis. PMID- 7989523 TI - Cumulative conception and live birth rates after the treatment of anovulatory infertility: safety and efficacy of ovulation induction in 200 patients. AB - An analysis was performed on the cumulative conception rates, cumulative live birth rates and adverse effects of ovulation induction in patients with anovulatory infertility attending a single unit over an 11-year period. A total of 200 patients were included, 103 with clomiphene-resistant polycystic ovary syndrome (PCOS), 77 with hypogonadotrophic hypogonadism (HH) and 20 with weight related amenorrhoea (WRA). Ovulation induction was performed using a number of protocols in which pulsatile luteinizing hormone-releasing hormone was administered s.c. or i.v. and gonadotrophins (human menopausal gonadotrophins or follicle-stimulating hormone) were administered i.m. The cumulative conception and live birth rates in the first course of therapy and after 12 cycles of treatment were, respectively, 73.2 and 62.4% in PCOS patients, 82.1 and 65.4% in the HH group and 95.0 and 85.3% in the WRA group. The miscarriage rates for all courses of treatment were 15.5% in PCOS patients, 22.9% in HH patients and 32.3% in WRA patients which resulted in cumulative live birth rates that were not significantly different. The median number of cycles and ovulations to achieve a pregnancy was 2 in all groups. The multiple pregnancy rate was significantly greater in women with PCOS (17.9%) than in women with HH (3.6%, P = 0.0052, 95% CI 5.12-23.36%) but not WRA (3.2%, P = 0.07, 95% CI 4.35-24.92%). The rate of multiple pregnancy fell after the introduction of monitoring by transvaginal ultrasound. Correction of anovulatory infertility by appropriately selected ovulation induction regimens results in cumulative conception and live birth rates indistinguishable from normal. PMID- 7989524 TI - Factors affecting pregnancy success of human in-vitro fertilization in unstimulated cycles. AB - Successful pregnancies have recently been reported in cycles of unstimulated in vitro fertilization (IVF) which is a simplification of the standard IVF approach utilizing ovarian stimulation. The purpose of this study was to analyse retrospectively the results of the first 3 years of unstimulated IVF cycles at our institution in order to identify factors which predispose these cycles to success or failure. All patients (n = 57) underwent serial monitoring with transvaginal ultrasound and serum oestradiol determinations. Human chorionic gonadotrophin (HCG) 10,000 IU was administered when follicles were felt to be mature and aspiration undertaken (n = 98) 34-36 h later. Among nine patients aged > or = 40 years, 13 aspirations resulted in nine embryo transfers and no pregnancies. In one completed cycle in this group, the patient, who was 42 years old had a baseline follicle stimulating hormone (FSH) concentration of 35.3 mIU/ml. The cycle progressed uneventfully and follicle aspiration yielded two oocytes and two morphologically normal embryos which, however, did not implant. In six patients < 40 years with male factor, seven aspirations yielded 18 oocytes of which 15 were inseminated and did not fertilize. One of the immature oocytes was allowed to mature in vitro and was fertilized and cryopreserved. Its transfer in a subsequent cycle yielded a live birth. Among 78 cycles in 42 patients aged < 40 years without male factor, 63 resulted in embryo transfer with 14% clinical pregnancy rates per aspiration and 17% per embryo transfer. Pregnancy was associated with higher oestradiol concentrations at the time of HCG administration and multiple embryos available for embryo transfer.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7989525 TI - Treatment of interstitial pregnancy with methotrexate: report of an unsuccessful case. AB - Until now, the traditional management of interstitial pregnancy has been surgical. Lately, we have advocated conservative treatment with methotrexate as an option for infertility patients. This is the first publication of a rupture with abundant intra-abdominal bleeding during systemic treatment with methotrexate of a patient with an interstitial pregnancy. Signs of therapy failure are discussed. PMID- 7989526 TI - Intra-uterine insemination, cervical pregnancy and successful treatment with methotrexate. AB - Cervical pregnancy is rare but one of the most dangerous of all pregnancy complications. The aetiology of cervical implantation is unclear and because of the fear of profuse haemorrhage abdominal hysterectomy has been historically considered the standard therapy. We report here an unusual case of an infertile woman with cervical ectopic pregnancy after ovulation induction with gonadotrophins and intrauterine insemination. The patient was successfully treated with parenteral methotrexate without significant morbidity. It is concluded that chemotherapy should be initially considered in most cervical pregnancies either as the sole form of treatment or to improve the chances of success in alternative conservative measures. PMID- 7989527 TI - Treatment of ectopic pregnancy: ablate or relocate--the newest dilemma? PMID- 7989528 TI - Evaluation of allergic and serological tests for diagnosing Brucella melitensis infection in sheep. AB - A total of 291 unvaccinated sheep from Brucella melitenesis-infected flocks were examined for delayed-type hypersensitivity (DTH) responses with Brucellergene commercial allergen and with cold saline extract and cytosol from rough B. melitensis 115, and their sera were tested in the rose bengal test (RBT), complement fixation test (CFT), and enzyme-linked immunosorbent assay (ELISA) with lipopolysaccharide. DTH reactions were maximal after 72 h, with no intensity differences among allergens, inoculation sites (eyelid and tail), and doses tested. There were no differences in the results recorded by visual inspection and palpation of inoculation sites, by measuring skin thickness with a caliper, or by microscopic examination of samples taken at necropsy. Six days after DTH testing, energy was observed in 100% of the animals, and 100% reactivity was recovered only after 24 days. All animals were necropsied, and thorough bacteriological searches were performed. The sensitivities found with the 140 animals from which B. melitensis was isolated were ELISA, 100%; DTH, 97.1%; RBT, 92.1%; and CFT, 88.6%. Those results put into question the value of RBT and CFT as screening and confirmatory tests for sheep brucellosis and at least indicate that their standardization should be modified. For 151 tested sheep from which B. melitensis was not isolated, the percentages of positive animals were ELISA, 100%; DTH, 94.0%; RBT, 57.6%; and CFT, 53.6%. All tests were negative for 100 tested sheep from Brucella-free flocks. The different results of bacteriological and immunological tests suggest the usefulness of developing indirect tests able to distinguish truly infected animals from those that have developed an immunological response. PMID- 7989529 TI - Astrovirus as a cause of gastroenteritis in Japan. AB - We used an enzyme immunoassay (EIA) to screen for astrovirus in stool specimens from outbreaks and sporadic cases of gastroenteritis collected between 1982 and 1992 in six prefectural public health institutes in Japan. Three outbreaks of gastroenteritis involving schoolchildren and adults were confirmed to be attributable to astrovirus. Astrovirus was detected in 6 to 10% of the specimens from patients with sporadic gastroenteritis from whom no other bacterial or viral agent had been identified. Among the sporadic cases, astrovirus was most frequently detected in infants less than 1 year of age, and the incidence peaked in March and April. Using specimens from recent outbreaks, we found that the EIA was more sensitive than electron microscopy (EM) for the detection of astrovirus, and many EM-negative specimens were positive by EIA. However, some stool specimens previously found to have astrovirus-like particles by EM were negative by EIA, perhaps because of inadequate storage conditions, such as long-term storage and repeated freezings and thawings. Our results indicate that astrovirus is more commonly associated with childhood gastroenteritis than has been previously appreciated and suggest that further studies to examine the epidemiology and disease burden of this virus are needed. PMID- 7989530 TI - Evaluation of Etest for rapid susceptibility testing of Mycobacterium chelonae and M. fortuitum. AB - Etest is a new concept for MIC determinations for antimicrobial agents that is based on a predefined antibiotic gradient on a plastic strip calibrated with a continuous logarithmic MIC scale covering 15 twofold dilutions. Etest was compared with a reference agar dilution method for susceptibility testing of clinical isolates of Mycobacterium chelonae and M. fortuitum. Results read after 3 days showed good agreement between MICs obtained with Etest and those obtained with the reference method within +/- 2 dilutions for 90% of all test combinations. All but one of the strains were inhibited by low concentrations of ciprofloxacin or amikacin. Susceptibility to clarithromycin, erythromycin, imipenem, rifampin, doxycycline, and fusidic acid was variable, and all strains were resistant to ceftazidime and trimethoprim. The results suggest that Etest is well suited for studies of drug resistance in rapidly growing mycobacteria. PMID- 7989531 TI - Biochemical identification of citrobacteria in the clinical laboratory. AB - We biochemically identified 235 Citrobacter strains to the species level on the basis of the recently proposed taxonomic changes of Brenner et al. (D. J. Brenner, P. A. D. Grimont, A. G. Steigerwalt, G. R. Fanning, E. Ageron, and C. F. Riddle, Int. J. Syst. Bacteriol. 43:645-658, 1993). Citrobacter isolates were initially identified as C. koseri or as members of the C. freundii complex or C. amalonaticus group on the basis of indole production, formation of H2S, malonate utilization, and acid production from D-arabitol and adonitol. On the basis of the results of these tests, 68% of the Citrobacter strains were identified as members of the C. freundii complex, 25% were C. koseri, and 8% were members of the C. amalonaticus group. By using a 15-test system recently proposed by Brenner et al. (D. J. Brenner, P. A. D. Grimont, A. G. Steigerwalt, G. R. Fanning, E. Ageron, and C. F. Riddle, Int. J. Syst. Bacteriol. 43:645-658, 1993) to help identify new species in the C. freundii complex and C. amalonaticus group, 81% of the C. freundii complex strains and 100% of the C. amalonaticus strains could be definitively assigned to one of the previously established or recently designated species or hybridization groups of the genus Citrobacter. Within the C. freundii complex, C. freundii predominated overall (37%), followed by C. youngae (24%), C. braakii (13%), and C. werkmanii (6%). Only one strain each of C. sedlakii and Citrobacter DNA group 11 was identified in this study. Among C. amalonaticus complex members, all were identified as C. amalonaticus with the singular exception of one fecal isolate of C. farmeri. C. freundii and C. koseri were the two Citrobacter species most commonly (80 of 93 [86%]) isolated from extraintestinal sources (genitourinary tract, wounds, blood). PMID- 7989532 TI - Gas chromatographic determination of D-arabinitol/L-arabinitol ratios in urine: a potential method for diagnosis of disseminated candidiasis. AB - A gas chromatographic procedure was developed to determine the relative amounts of D- and L-arabinitol in urine. Samples were filtered, diluted, purified through extractions, evaporated, and treated with trifluoroacetic anhydride; the arabinitol derivatives thus obtained were separated on a chiral stationary phase and registered by using an electron-capture detector. Urine samples from a patient with disseminated candidiasis had higher D-arabinitol/L-arabinitol ratios (referred to as D/L-arabinitol ratios)--up to 19.0--than samples from 96 study individuals with no signs of deep Candida infections (range, 1.1 to 4.5). D/L Arabinitol ratios in urine samples from hospitalized patients without Candida infections were slightly higher than those in samples from healthy individuals; ratios in urine from children were slightly higher than those in adult urine samples. The D/L-arabinitol ratios in several urine samples culture positive for Candida albicans, but from patients without symptoms of disseminated candidiasis, did not differ from those in the urine of healthy individuals. The described gas chromatographic method is straightforward and can be implemented clinically to determine urine D/L-arabinitol ratios as a means of diagnosing disseminated candidiasis. PMID- 7989533 TI - Genomic diversity among Corynebacterium jeikeium strains and comparison with biochemical characteristics and antimicrobial susceptibilities. AB - Levels of DNA relatedness were determined by performing DNA-DNA hybridization experiments (S1 nuclease procedure) with 13 human isolates exhibiting various antimicrobial susceptibility patterns which had been identified as Corynebacterium jeikeium by classical tests and the API Coryne system and with reference strains of C. jeikeium and related taxa. Twelve of 13 isolates which formed three genomic groups showed between 22 and 75% relatedness with the type strain of C. jeikeium. One of these genomic groups included all the strains resistant to penicillin and gentamicin and is genomically related to the C. jeikeium type strain at the species level. In addition, the reference strain of "Corynebacterium genitalium" biotype II was found to belong to this genospecies and therefore can be considered as a synonym of C. jeikeium. In contrast, one isolate and the reference strains of "Corynebacterium pseudogenitalium" biotypes C-3 and C-4 which were assigned to C. jeikeium by the API Coryne system were less than 10% related to the C. jeikeium type strain. These nongenomically related strains can be differentiated from the jeikeium-related strains on the basis of positive acidification from fructose and growth under anaerobic conditions. Furthermore, these strains exhibited full susceptibility to penicillin whereas the strains related to the C. jeikeium type strain are resistant to or only moderately susceptible to penicillin. No genomic relationship was found between C. jeikeium-related strains and other lipophilic coryneforms, identified as Corynebacterium accolens or Corynebacterium group G or F. Our study demonstrates the necessity to perform the fructose fermentation test or respiratory-type test for the correct identification of lipophilic coryneforms as C. jeikeium. Although these strains show genomic diversity at the species level, in a practical aspect, biochemical properties as well as antimicrobial susceptibility may allow the classification of such isolates in this single taxon. PMID- 7989535 TI - Comparative evaluation of molecular typing of strains from a national epidemic due to Salmonella brandenburg by rRNA gene and IS200 probes and pulsed-field gel electrophoresis. AB - In Switzerland in 1992 there was a prolonged series of outbreaks of human salmonellosis caused by a previously rare serotype, Salmonella brandenburg. In order to examine the genotypic basis of the epidemic, molecular typing was applied to representative strains of this serovar isolated between 1983 and 1992. These included sporadic human isolates up to 1985, isolates from unrelated geographical areas, and Swiss isolates from humans, animals, and meat products isolated after 1991. Plasmid profiling was not found to be applicable to S. brandenburg, but chromosomal typing was accomplished by analyzing restriction fragment length polymorphisms with DNA probes for three marker loci; the 16S and 23S rRNA genes and sites of insertion of the mobile DNA element IS200. The macrorestriction profiles of the whole genome were examined by pulsed-field gel electrophoresis, which proved to be the most discriminatory of the typing methods. The study demonstrated the comparative value and complementary relationship between these typing methods for epidemiological purposes. All approaches concurred in identifying the 1992 isolates as a single genotypic clone, which was present in multiple (food) vehicles of infection. They were distinct from sporadic isolates of this serovar and from strains of S. brandenburg isolated in other countries. PMID- 7989534 TI - Development of enzyme-labeled oligonucleotide probe for detection of mecA gene in methicillin-resistant Staphylococcus aureus. AB - A DNA hybridization method with an enzyme-labeled oligonucleotide probe (mecA ELONP) was developed to detect the methicillin-resistant gene (mecA) in methicillin-resistant Staphylococcus aureus. For rapid identification, bacterial colonies were transferred from agar plates directly onto nylon membranes. Lysis of cells, denaturation of DNA, and hybridization were performed on the membranes. These procedures required only 3 h for completion. The results obtained by this test closely corresponded with those obtained by determining the MICs of oxacillin against S. aureus. The results of the mecA-ELONP also correlated well with those of a commercially available PCR test. Thus, mecA-ELONP proved to be a reliable and convenient method for the rapid identification of methicillin resistant S. aureus, which could be useful in clinical microbiology laboratories. PMID- 7989536 TI - Detection of herpes simplex virus DNA from cerebrospinal fluid by PCR and a rapid, nonradioactive hybridization technique. AB - A molecular assay for the detection of herpes simplex virus (HSV), including a novel, nonradioactive hybridization technique, was evaluated with a total of 123 cerebrospinal fluid specimens. After DNA extraction, specific HSV DNA sequences were amplified with digoxigenin-labeled primers derived from the DNA polymerase gene-coding region from HSV. Amplified products were detected by the Enzymun-Test DNA detection assay (Boehringer, Mannheim, Federal Republic of Germany), which uses biotinylated probes. Amplification with nonlabeled primers and then Southern blotting and nonradioactive detection of hybrids by the digoxigenin technique was the reference system. The sensitivities of the molecular assays were determined with 10-fold dilutions of plasmid pS4 with the SalI restriction fragment of the DNA polymerase gene obtained from the HSV type 1 strain Angelotti. The Enzymun assay was able to detect all of the 16 positive samples, giving 100% agreement with the Southern blot hybridization results. Optical density values were widely separated for the positive and negative groups of specimens. Ten copies of plasmid pS4 per microliter could be distinctly detected by the Enzymun assay. The cutoff was determined for the hybridization assay, and an equivocal zone was defined. The whole molecular assay including the Enzymun-Test DNA detection proved to be sensitive and easy to use. It may contribute to the rapid and safe detection of HSV DNA in cerebrospinal fluid. PMID- 7989537 TI - Automated quantitative determination of hepatitis C virus viremia by reverse transcription-PCR. AB - An automated reverse transcription-PCR was developed for the quantitative detection of hepatitis C virus. The quantitation is based on the coamplification and labelling with digoxigenin-dUTP during PCR of two similar templates, the viral genome and a modified RNA which acts as a mimic target. Known amounts of the mimic RNA sequence were introduced into the clinical samples. The automated quantitation of the two coamplified and labelled products depends on the use of two biotinylated caputre probes which are complementary, respectively, to a deleted sequence and to an inserted sequence introduced by site-directed mutagenesis in a wild viral cloned cDNA. This method proved to be simple, reproducible, and useful for quantitate hepatitis C virus viremia in chronically infected patients. This easy-to-perform, automated assay could also be used for the accurate determination of human immunodeficiency virus viremia or other RNA molecules. PMID- 7989539 TI - Detection of Brucella melitensis by BACTEC NR660 blood culture system. AB - Data on the performance of modern blood culture systems for the detection of Brucella spp. are insufficient. To evaluate the performance of the BACTEC NR660 blood culture system for the detection of Brucella melitensis within the routine 1-week blood culture protocol, a prospective 24-month study was conducted in an area endemic for B. melitensis in southern Israel. Blood samples obtained from patients with suspected brucellosis were monitored and blindly subcultured once per week for 4 weeks, and the fraction of blood cultures positive for B. melitensis detected by the BACTEC NR660 instrument within the first week was determined. During the study period, a total of 373 blood cultures were obtained from patients in whom brucellosis was suspected, and 27 (7.2%) of them, drawn from 21 different patients, were positive for B. melitensis. Twenty-one (78.8%) of these positive cultures were detected by the BACTEC instrument within 7 days, and six positive cultures were detected by subculture after 2 or 3 weeks of incubation. It is concluded that the BACTEC NR660 blood culture system detects the majority of B. melitensis isolates within the routine 1-week blood culture schedule. To maximize the recovery of the organism, however, prolonged incubation and periodic performance of blind subcultures are still required. PMID- 7989538 TI - Detection of leptospires in urine by PCR for early diagnosis of leptospirosis. AB - We tested urine samples from patients at different stages of current leptospirosis and thereafter to determine whether use of the PCR for detection of leptospires in urine can be a valuable alternative to culturing. The procedure of DNA extraction and subsequent PCR applied to 15 freshly voided urine samples proved to be twice as sensitive as culturing. Overall, we were able to detect leptospires in approximately 90% (26 of 29) of the urine samples. Urine and serum samples were obtained from seven patients, before the eighth day of illness. Although it is generally assumed that leptospiruria starts approximately in the second week of illness, we were able to detect leptospires in all of these early urine samples. In contrast, only two of seven corresponding serum samples gave positive PCR results, which suggests that PCR analysis of urine can be more successful for early diagnosis of leptospirosis than PCR analysis of serum. Urine samples from six patients who had been treated with antibiotics at the time of illness were positive by PCR, implying that the patients were still shedding leptospires in their urine despite treatment. Some of these samples were even taken years after the infection, indicating that shedding of leptospires in urine may last much longer than is generally assumed. We conclude that detection of leptospires in urine with PCR is a promising approach for early diagnosis of leptospirosis and may also be useful in studying long-term shedding. PMID- 7989540 TI - Rapid detection and identification of Candida albicans and Torulopsis (Candida) glabrata in clinical specimens by species-specific nested PCR amplification of a cytochrome P-450 lanosterol-alpha-demethylase (L1A1) gene fragment. AB - PCR of a Candida albicans cytochrome P-450 lanosterol-alpha-demethylase (P450 L1A1) gene segment is a rapid and sensitive method of detection in clinical specimens. This enzyme is a target for azole antifungal action. In order to directly detect and identify the clinically most important species of Candida, we cloned and sequenced 1.3-kbp fragments of the cytochrome P450-L1A1 genes from Torulopsis (Candida) glabrata and from Candida krusei. These segments were compared with the published sequences from C. albicans and Candida tropicalis. Amplimers for gene sequences highly conserved throughout the fungal kingdom were first used; positive PCR results were obtained for C. albicans, T. glabrata, C. krusei, Candida parapsilosis, C. tropicalis, Cryptococcus neoformans, and Trichosporon beigelii DNA extracts. Primers were then selected for a highly variable region of the gene, allowing the species-specific detection from purified DNA of C. albicans, T. glabrata, C. krusei, and C. tropicalis. The assay sensitivity as tested for C. albicans in seeded clinical specimens such as blood, peritoneal fluid, or urine was 10 to 20 cells per 0.1 ml. Compared with results obtained by culture, the sensitivity, specificity, and efficiency of the species specific nested PCR tested with 80 clinical specimens were 71, 95, and 83% for C. albicans and 100, 97, and 98% for T. glabrata, respectively. PMID- 7989542 TI - Detection of type A, B, and E botulism neurotoxin genes in Clostridium botulinum and other Clostridium species by PCR: evidence of unexpressed type B toxin genes in type A toxigenic organisms. AB - We studied the effectiveness of the PCR in detecting the type A, B, and E botulism neurotoxin genes in 209 strains of Clostridium botulinum and 29 strains of other Clostridium spp. All 79 strains that produced type A toxin, 77 strains that produced type B toxin, and 51 organisms that produced type E toxin (46 C. botulinum and 5 C. butyricum) were PCR positive in reactions with primers targeting sequences specific for their respective toxin genes. The PCR for type A toxin was positive for one type B toxin-producing strain that produced a small amount of type A toxin in addition to a large amount of type B toxin. Surprisingly, the type B toxin gene was detected in addition to the type A toxin gene in 43 type A toxin-producing strains, only 1 of which could be shown by bioassay to produce biologically active type B toxin in culture. The type B gene was also detected in two strains of C. subterminale, which were determined to be nontoxigenic by bioassay. While the PCR was sensitive and specific in detecting the neurotoxin genes, the discovery of unexpressed toxin genes indicates that PCR results may not be adequate for establishing type B neurotoxigenicity. PMID- 7989541 TI - Gas-liquid chromatography of cellular fatty acids for identification of staphylococci. AB - A commercially available, computer-assisted microbial identification system (MIS) employs gas-liquid chromatographic analyses of bacterial fatty acids. The MIS was used to identify 470 isolates of Staphylococcus species. The accuracy of the MIS was compared with the accuracies of conventional methods. There was a complete agreement between the MIS and conventional methods in the identification of 413 (87.8%) strains. For 36 of 45 misidentified strains, the correct identification was listed by the MIS as a choice but not as the first choice. Twelve strains could not be matched. All strains of Staphylococcus cohnii, S. epidermidis, S. intermedius, S. lugdunensis, S. schleiferi, S. sciuri, S. simulans, and S. xylosus were correctly identified. Two species, S. hominis and S. saprophyticus, accounted for 52.6% (30 of 57) of the misidentifications. Seventy-eight organisms were retested. Identification of 73 organisms remained unchanged, and for five organisms, the second choice became first and vice versa. The overall performance of the MIS is acceptable, and the system can be used as an alternate identification method for staphylococci. PMID- 7989543 TI - Recognition of Dermabacter hominis, formerly CDC fermentative coryneform group 3 and group 5, as a potential human pathogen. AB - Thirty strains of fermentative coryneform-like bacteria designated CDC fermentative coryneform group 3 and coryneform group 5 were compared biochemically by cellular fatty acid analysis and by DNA relatedness with the type strain of Dermabacter hominis, ATCC 49369. DNA from 22 strains of both CDC groups showed 69 to 96% relatedness (hydroxyapatite method) to labeled DNA from ATCC 49369 and to DNA from CDC group 3 strain G4964, and the strains are considered to belong to D. hominis. The remaining eight strains were genetically but not phenotypically differentiable from D. hominis. They were genetically heterogeneous, but hybridization results indicated that they probably belong to the genus Dermabacter. Thirteen of the 22 D. hominis strains and all 8 of the other Dermabacter strains had been isolated from blood, which indicates the pathogenic potential of this species and genus. PMID- 7989544 TI - CHROMagar Candida, a new differential isolation medium for presumptive identification of clinically important Candida species. AB - CHROMagar Candida is a novel, differential culture medium that is claimed to facilitate the isolation and presumptive identification of some clinically important yeast species. We evaluated the use of this medium with 726 yeast isolates, including 82 isolated directly on the medium from clinical material. After 2 days of incubation at 37 degrees C, 285 C. albicans isolates gave distinctive green colonies that were not seen with any of 441 other yeast isolates representing 21 different species. A total of 54 C. tropicalis isolates also developed distinctive dark blue-gray colonies with a halo of dark brownish purple in the surrounding agar. C. krusei isolates (n = 43) also formed highly characteristic rough, spreading colonies with pale pink centers and a white edge that was otherwise encountered only rarely with isolates of C. norvegensis. Trichosporon spp. (n = 34) formed small, pale colonies that became larger and characteristically rough with prolonged incubation. Most of the other 310 yeasts studied formed colonies with a color that ranged from white to pink to purple with a brownish tint. The only exceptions were found among isolates identified as Geotrichum sp. or Pichia sp., some of which formed colonies with a gray to blue color and which in two instances formed a green pigment or a dark halo in the agar. The specificity and sensitivity of the new medium for the presumptive identification of C. albicans, C. krusei, and C. tropicalis exceeded 99% for all three species. A blinded reading test involving four personnel and 57 yeast isolates representing nine clinically important species confirmed that colonial appearance after 48 h of incubation on CHROMagar Candida afforded the correct presumptive recognition of C. albicans, C. tropicalis, C, krusei, and Trichosporon spp. None of nine bacterial isolates grew on CHROMagar Candida within 72 h, and bacteria (Escherichia coli) grew from only 4 of 104 vaginal, 100 oral, and 99 anorectal swabs. The new medium supported the growth of 19 of 23 dermatophyte fungi tested and 41 of 43 other molds representing a broad range of fungal pathogens and contaminants. In parallel cultures of 348 clinical specimens set up on Sabourand agar and CHROMagar Candida, both media grew yeasts in the same 78 instances. CHROMagar Candida is recommended as a useful isolation medium capable of the presumptive identification of the yeast species most commonly isolated from clinical material and facilitating recognition of mixed yeast cultures. PMID- 7989545 TI - Detection of cilia-associated respiratory bacillus by PCR. AB - The cilia-associated respiratory (CAR) bacillus is an unclassified, gram negative, motile bacterium that has been implicated as an etiologic agent of respiratory disease in laboratory rodents. In the present study, approximately 1,200 bases of the 16S rRNA gene from three CAR bacillus isolates were sequenced. CAR bacillus-specific primers were designed on the basis of the 16S rRNA gene sequence and used in a PCR assay. The PCR assay detected as little as 500 fg of purified CAR bacillus DNA. The expected 267-bp DNA fragment was amplified from respiratory tissue of frozen, formalin-fixed, and paraffin-embedded samples from experimentally and naturally infected rats and mice. In contrast, no product was amplified from respiratory tissues of sham-infected experimental animals or animals that were serologically or histopathologically negative for the CAR bacillus. Our findings indicate that this PCR assay is a rapid, specific, and sensitive detection method for the diagnosis of CAR bacillus infection in rats and mice. PMID- 7989547 TI - Typing of group A streptococci by random amplified polymorphic DNA analysis. AB - Random amplified polymorphic DNA (RAPD) analysis was evaluated in comparison with restriction endonuclease analysis (REA) of genomic DNA and serotyping in the typing of 160 epidemiologically unrelated group A streptococci (GAS). Amplification of genomic DNA of GAS was performed with a single primer with an arbitrarily selected nucleotide sequence of 12 nucleotides. In total, 31 RAPD patterns and 15 REA patterns were observed among the isolates studied. The results of RAPD analysis were in accordance with the results of REA for 86% of the isolates, as both methods identified 15 different strains among 138 isolates. However, RAPD analysis differentiated 16 additional strains among 22 isolates. RAPD analysis was somewhat better than REA for differentiation of isolates of the same and different serotypes. However, not all of the serotypes were differentiated by RAPD analysis either. In conclusion, RAPD analysis provides a practical alternative for genomic typing of GAS. It can be recommended for the typing of GAS, especially if used in parallel with serotyping. PMID- 7989546 TI - Use of PCR to study epidemiology of Serratia marcescens isolates in nosocomial infection. AB - A method to characterize strains of Serratia marcescens based on the PCR amplification of enterobacterial repetitive intergenic consensus sequences has been developed. The PCR fingerprints were generated from boiled supernatants prepared directly from bacterial colonies without the need for DNA extraction. The technique was applied to isolates obtained during an outbreak of pneumonia from seven mechanically ventilated patients, and its result indicated that the outbreak was due to the spread of two epidemic strains. This technique was validated by comparison with rRNA gene restriction analysis. There was complete concordance between these two techniques in discriminating the outbreak-related strains from epidemiologically unrelated isolates. Typing with both biochemical profile and antibiogram profile, though simple, was found to be less reliable than genotyping. The results show that this enterobacterial repetitive intergenic consensus PCR provides a rapid and simple means of typing S. marcescens isolates for epidemiologic studies. PMID- 7989548 TI - Characterization of Leptospira isolates from serovar hardjo by ribotyping, arbitrarily primed PCR, and mapped restriction site polymorphisms. AB - Leptospira serovar hardjo isolates of the hardjoprajitno and hardjobovis genotypes were characterized by ribotyping, arbitrarily primed PCR (AP-PCR) fingerprinting, and the study of mapped restriction site polymorphisms (MRSPs) in rrs and rrl genes. After restriction of chromosomal DNA with BglII, EcoRI, or HindIII, each genotype was individualized with a distinct ribotype. The fingerprints produced by AP-PCR with seven primers clearly separated the two groups; primers KF and RSP produced species-specific products which assigned hardjoprajitno and hardjobovis isolates to the species L. interrogans sensu stricto and L. borgpetersenii, respectively. Furthermore, AP-PCR fingerprints gave evidence of a considerable genomic heterogeneity at the strain level among the hardjobovis group. Conversely, the hardjoprajitno group was homogeneous. MRSP profiles in ribosomal genes indicated that hardjoprajitno and hardjobovis isolates belonged to L. interrogans MRSP group B and L. borgpetersenii group C, respectively. AP-PCR and determination of MRSPs in ribosomal genes proved to be quick and reliable methods for typing Leptospira strains and for studying intraspecific population structures. PMID- 7989550 TI - Comparison of restriction endonuclease analysis, ribotyping, and pulsed-field gel electrophoresis for molecular differentiation of Clostridium difficile strains. AB - A combined clinical and molecular epidemiologic analysis of 46 strains of Clostridium difficile, including 16 nosocomial isolates from one ward (outbreak ward) plus 17 other nosocomial isolates and 13 community-acquired isolates, was performed. HindIII digests of total cellular DNA were analyzed by restriction enzyme analysis (REA) and ribotyping; SmaI digests were analyzed by pulsed-field gel electrophoresis (PFGE). Isolates were assigned to typing groups on the basis of the profiles detected; isolates with closely related profiles were assigned to subgroups. The 16 isolates from the outbreak ward were resolved by both REA and PFGE into five distinct groups; 13 isolates represented two REA groups and three PFGE groups and two isolates were resolved as distinct groups by both techniques. DNA obtained from one isolate was persistently partially degraded, precluding analysis by PFGE. Seventeen sporadic nosocomial isolates were resolved by REA and PFGE into comparable numbers of groups (i.e., nine groups) and subgroups (i.e., 15 and 14 subgroups, respectively), with two isolates not evaluable by PFGE. The 13 epidemiologically unrelated community-acquired isolates were assigned to 11 groups by REA and to 12 groups by PFGE. Overall, ribotyping identified only nine groups among the 46 isolates. We conclude that REA and PFGE have comparable discriminatory powers for epidemiologic typing of C. difficile isolates and that ribotyping is appreciably less discriminatory. For a few isolates, partial DNA degradation prevented analysis by PFGE but not by REA or ribotyping; the cause of the degradation is unknown. PMID- 7989549 TI - Comparison of four immunoserologic assays for detection of antibodies to Borrelia burgdorferi in patients with culture-positive erythema migrans. AB - In view of the significant sequelae associated with Lyme borreliosis, there is a need for timely and accurate diagnosis of erythema migrans (EM). Although Borrelia burgdorferi can be cultured from biopsies of EM lesions, immunodiagnostic testing is more widely available. Four immunoserologic methods were studied by using the sera of 51 patients with EM lesions that were culture positive for B. burgdorferi. Nineteen patients had single primary lesions, and thirty-two had multiple secondary lesions. At the time of biopsy, 40 patients, 8 with primary lesions and all patients with secondary lesions, were seropositive by an immunoglobulin M (IgM) indirect fluorescent-antibody (IgM IFA) test (Bion Enterprises). Twenty-three patients were seropositive by a whole-cell fluorescence enzyme immunoassay (EIA) (BioWhittaker, Inc.), twenty-two were positive by immunoblotting (ViroStat, Inc.), and one was positive by a P39 recombinant EIA (P39 EIA) (General Biometrics, Inc.). Sera from various patient control groups were tested: rheumatoid arthritis (n = 19), infectious mononucleosis (n = 20), systemic lupus (n = 22), syphilis (n = 13), streptococcal sequelae (n = 20), and healthy subjects (n = 16). None of these sera reacted with the IgM IFA test or P39 EIA. Fifteen reacted with the fluorescence EIA. We conclude that the IgM IFA test is an effective and reliable assay for the diagnosis of EM, particularly for patients with secondary lesions. Immunoblot, fluorescence EIA, and P39 EIA lack the sensitivity to reliably diagnose EM. PMID- 7989552 TI - Evaluation of microagglutination test for differentiation between Serpulina (Treponema) hyodysenteriae and S. innocens and serotyping of S. hyodysenteriae. AB - Swine dysentery is a mucohemorrhagic diarrheal disease caused by the anaerobic spirochete Serpulina hyodysenteriae. At present, the serotyping is done by immunodiffusion testing with lipopolysaccharide (LPS) extract as antigen and rabbit hyperimmune sera produced against different serotypes of S. hyodysenteriae. Since the preparation of LPS is time-consuming and requires a large quantity of bacteria, it is desirable to use a serotyping method which does not require the extraction of LPS. In the present investigation, microagglutination was evaluated by using both formalinized whole- and boiled cell suspensions as antigens and rabbit hyperimmune sera produced against formalinized whole-cell suspensions of reference strains of S. hyodysenteriae and S. innocens B256. Use of boiled cell suspension as antigen permitted the differentiation between isolates of S. hyodysenteriae and S. innocens as well as serotyping of S. hyodysenteriae strains accurately. A total of 18 isolates were identified as S. hyodysenteriae, and 3 isolates were identified as S. innocens. The microagglutination test was found specific, sensitive, and easy to perform; thus, it was judged suitable for routine identification and serotyping of S. hyodysenteriae isolates. PMID- 7989551 TI - Evaluation of Biolog system for identification of some gram-negative bacteria of clinical importance. AB - The Biolog system (Biolog, Inc., Hayward, Calif.) was evaluated for the identification of 55 gram-negative taxa (789 strains) likely to be encountered commonly in clinical laboratories. The Biolog system performed best with oxidase positive fermenters and biochemically active nonfermenters and had the most problems with unreactive nonfermenters. It gave significantly better results when the MicroPlates were read manually rather than when they were read by the automated reader. Plates read manually gave the following performances: oxidase positive fermenters, five taxa, 64 strains, 92% correct, 3% not identified, and 5% incorrect; biochemically active nonfermenters, eight taxa, 122 strains, 88% correct, 6% not identified, and 6% incorrect; members of the family Enterobacteriaceae, 35 taxa, 511 strains, 77% correct, 8% not identified, and 15% incorrect; unreactive nonfermenters, seven taxa, 92 strains, 38% correct, 24% not identified, and 38% incorrect. We found the system easy to use, but while for 39 of 55 of the taxa an identification rate of > 70% was achieved, problems were encountered, particularly with identification of capsulated strains of some Enterobacter and Klebsiella taxa, as well as the least biochemically active Moraxella and Neisseria strains. PMID- 7989553 TI - Enzyme-linked immunosorbent assay for measuring ileal symbiont intracellularis specific immunoglobulin G response in sera of pigs. AB - Proliferative enteritis (PE) is a common intestinal disease on pig farms. The disease is caused by ileal symbiont (IS) intracellularis (Campylobacter-like organisms) bacteria. An enzyme-linked immunosorbent assay (ELISA) was developed to measure IS intracellularis-specific immunoglobulin G (IgG) response in the sera of pigs. The antigen used in the ELISA was filtered, percoll gradient purified IS intracellularis extracted from the intestines of pigs affected with proliferative hemorrhagic enteropathy. The antibody responses of pigs challenged with intestinal homogenates from pigs affected with proliferative hemorrhagic enteropathy containing IS intracellularis or percoll-gradient purified IS intracellularis were low and variable. The low IgG titers measured in challenged pigs support previous findings that IgG plays a minor role in the immune response of pigs to IS intracellularis. On a farm in which infection was endemic, pigs seroconverted at between 7 and 24 weeks of age. High IgG titers, indicative of maternally acquired antibody, were present in 3-week-old pigs. The IgG titers in piglets were lowest at 6 weeks of age, which approximates the age of onset of clinical disease. These results suggest that IgG plays a role in determining the susceptibilities of pigs to natural infection. Measurements of seroconversion by the ELISA might aid in epidemiological investigations of PE in naturally infected herds. However, the variable antibody responses in experimentally challenged pigs would seem to limit its usefulness as an antemortem diagnostic test for PE. PMID- 7989554 TI - Application of PCR to a clinical and environmental investigation of a case of equine botulism. AB - PCR for the detection of botulinum neurotoxin gene types A to E was used in the investigation of a case of equine botulism. Samples from a foal diagnosed with toxicoinfectious botulism in 1985 were reanalyzed by PCR and the mouse bioassay in conjunction with an environmental survey. Neurotoxin B was detected by mouse bioassay in culture enrichments of serum, spleen, feces, and intestinal contents. PCR results compared well with mouse bioassay results, detecting type B neurotoxin genes in these samples and also in a liver sample. Other neurotoxin types were not detected by either test. Clostridium botulinum type B was shown to be prevalent in soils collected from the area in which the foal was raised. Four methods were used to test for the presence of botulinum neurotoxin-producing organisms in 66 soil samples taken within a 5-km radius: PCR and agarose gel electrophoresis (types A to E), PCR and an enzyme-linked assay (type B), hybridization of crude alkaline cell lysates with a type B-specific probe, and the mouse bioassay (all types). Fewer soil samples were positive for C. botulinum type B by the mouse bioassay (15%) than by any of the DNA-based detection systems. Hybridization of a type B-specific probe to DNA dot blots (26% of the samples were positive) and PCR-enzyme-linked assay (77% of the samples were positive) were used for the rapid analysis of large numbers of samples, with sensitivity limits of 3 x 10(6) and 3,000 cells, respectively. Conventional detection of PCR products by gel electrophoresis was the most sensitive method (300-cell limit), and in the present environmental survey, neurotoxin B genes only were detected in 94% of the samples. PMID- 7989555 TI - Evaluation of a novel colorimetric broth microdilution method for antifungal susceptibility testing of yeast isolates. AB - A comparative evaluation of two broth microdilution methods for antifungal susceptibility testing of 600 clinical yeast isolates (Candida spp., Torulopsis glabrata, and Cryptococcus neoformans) against amphotericin B, fluconazole, and flucytosine (5FC) was conducted. Microdilution testing was performed according to National Committee for Clinical Laboratory Standards (NCCLS) recommendations (NCCLS document M27-P). By using the growth control for comparison, reference microdilution MIC endpoints for amphotericin B were scored as the lowest concentration at which a score of 0 (complete absence of growth) was observed, and those for 5FC and fluconazole were scored at the lowest concentration at which a score of 2 (prominent decrease in turbidity) (MIC-2) was observed. The second microdilution method employed a colorimetric endpoint using an oxidation reduction indicator (Alamar Biosciences, Inc., Sacramento, Calif.) and was assessed independently of the reference microdilution MICs. The MICs for the two microdilution test systems were read after 24 and 48 h of incubation. Excellent agreement between the reference and colorimetric microdilution MICs was observed. Overall agreement was > or = 95% for all three drugs at 24 h. At 48 h, agreement was > or = 98% for amphotericin B and 5FC but dropped to 84% for fluconazole. Given these results it appears that the colorimetric microdilution approach to antifungal susceptibility testing may be viable alternative to the NCCLS reference method for testing yeasts. PMID- 7989556 TI - Application to immunoglobulin M capture hemadherence assays of hemagglutination of monkey erythrocytes by native and recombinant human parvovirus B19 antigens. AB - Human parvovirus B19 recently was shown to agglutinate baboon and human erythrocytes. We have now demonstrated that both recombinant and native B19 antigens agglutinate rhesus, cynomolgus, and Saimiri monkey erythrocytes. Using cynomolgus erythrocytes and the recombinant antigen, we developed an immunoglobulin M (IgM) antibody capture hemadherence test (MACHAT) for the detection of specific B19 IgM antibodies in human sera. The results obtained with MACHAT were compared with those obtained with an IgM capture enzyme immunoassay (MACEIA) employing the native antigen routinely used in our laboratory. For 229 patient serum samples, we found 96% agreement between the results of the two assays. There was some evidence that MACHAT was slightly more sensitive than MACEIA. Our results add to the range of erythrocytes that can be agglutinated by B19 virus and show that native as well as recombinant antigens may be used in MACHAT. PMID- 7989557 TI - Enzymatic amplification of lactate dehydrogenase-elevating virus. AB - To improve the detection of lactate dehydrogenase-elevating virus (LDV), we developed a PCR assay. Primers were selected from ORF7, encoding nucleocapsid protein VP1. No specific amplification was observed with any other common murine virus or with RNAs from the closely related Lelystad virus and equine arteritis virus. In experimentally infected mice, LDV could be detected in plasma in both the acute and the persistent phases. LDV was also detected by the PCR in contaminated pools of Plasmodium berghei parasites which were maintained in mice, both by a direct analysis of the samples and by testing of plasma from mice inoculated with these pools. There was a complete agreement between the results of the PCR assay and the lactate dehydrogenase (LDH) enzyme assay of plasma from the inoculated mice. In contrast to the results of the LDH enzyme assay, no false positive reactions were obtained in the PCR assay with negative control samples showing visible hemolysis. Storage of plasma samples at room temperature and at 4, -20, and -80 degrees C for up to 8 days did not influence the results of the PCR. These results show that the PCR is a valuable technique which may replace the LDH test as a diagnostic tool. PMID- 7989558 TI - Identification and elimination of DNA sequences in Taq DNA polymerase. AB - This study confirms that different preparations of Taq DNA polymerase are contaminated with eubacterial DNA. The contaminants appeared to represent more than one strain or species but were not identified as Thermus aquaticus or Escherichia coli. Differences in microcentrifuge tube composition appeared to affect elimination of the contaminants. PMID- 7989560 TI - Surveillance of susceptibility testing methodologies for Haemophilus influenzae in Canada, including evaluation of disk diffusion test. AB - We surveyed 75 clinical laboratories to determine if National Committee for Clinical Laboratory Standards (NCCLS) were being used for the susceptibility testing of Haemophilus influenzae. Of the 66 laboratories that performed susceptibility testing, all claimed to follow current NCCLS guidelines. However, upon further questioning, only 23, all of which used disk diffusion testing, accurately interpreted and followed the guidelines. Proficiency testing of 22 of these laboratories found that an unacceptable number of interpretive errors (> 10%) occurred. These results query the merit of routine disk diffusion susceptibility testing of H. influenzae to beta-lactam agents. PMID- 7989559 TI - Genetic analysis of equine rotavirus by RNA-RNA hybridization. AB - Serotype G3 equine rotaviruses isolated in Japan made up a common genogroup and were classified into two different genotypes. The genomes of serotype G3 equine rotaviruses with an identical electropherotype (isolated from 1982 to 1989) were very closely related to each other regardless of the year in which they were isolated. Serotype G3 equine rotavirus BI originating from England belonged to the same genogroup of serotype G3 equine rotaviruses isolated in Japan, although BI was classified as having a different genotype. The genomes of both serotype G10 equine rotavirus R-22 and serotype G10 calf rotavirus were closely related to each other. PMID- 7989561 TI - Differential susceptibilities of enterococcal species to elfamycin antibiotics. AB - The elfamycins are a class of naturally occurring antibiotics not currently used in the therapy of human disease. Enterococcus faecium and closely related species (Enterococcus durans and Enterococcus hirae) are susceptible to these antibiotics, while isolates of Enterococcus faecalis and other enterococcal species are highly resistant. Among enterococci, susceptibility or resistance to elfamycins appears to be determined by the bacterial protein synthesis elongation factor EF-Tu. Elfamycin susceptibility may be a useful adjunct for rapidly distinguishing E. faecalis and E. faecium in the clinical microbiology laboratory and/or as a supplementary test for use in determining the species of enterococci. PMID- 7989562 TI - Clear broth and plate media for culture of Haemophilus ducreyi. AB - Using catalase as a source of heme, we have developed both clear plate and broth media for the growth of Haemophilus ducreyi, the causative agent of chancroid. In the broth medium, the growth phase of the organism can be monitored and the organisms achieve a cell density of > 10(8) CFU/ml. PMID- 7989563 TI - Effects of enhancing agents on detection of cytomegalovirus in clinical specimens. AB - Dimethyl sulfoxide, dexamethasone, and calcium were tested in combination for their enhancing effects on cytomegalovirus detection in shell vial cultures on 1,579 clinical specimens obtained primarily from adult solid-organ transplant recipients. Fluorescent-focus counts were elevated for the cytomegalovirus positive urine specimens (P < 0.01) and throat washings (P < 0.05) but not for the tissue biopsy or blood samples. Epidermal growth factor also increased focus counts but provided no additional benefit when used in combination with the other agents. The triple-combination treatment did not increase the number of positive specimens identified. PMID- 7989564 TI - Biodegradable, effective substitute for xylene in the Ehrlich indole procedure. AB - Three extracting reagents were compared for effectiveness in the Ehrlich indole procedure: xylene (the recommended reagent), Hemo-De (a terpene-based product containing d-limonene), and Micro-Clear (an isoparaffinic hydrocarbon). Thirty three strains representing 12 species of indole-positive aerobes or facultative anaerobes and 50 strains representing 11 species of indole-positive strict anaerobes were tested using the three reagents. Xylene extraction allowed indole detection in all of the isolates tested. Micro-Clear allowed detection in all of the aerobic isolates and in 49 of 50 anaerobes. Hemo-De allowed indole detection in 32 of 33 aerobes and in 49 of 50 anaerobes. There was no significant difference in the results among the reagents. Because Micro-Clear is biodegradable, nonflammable, noncarcinogenic, and odorless, we feel that this product should be considered a safe and effective substitute for xylene in the Ehrlich indole procedure. PMID- 7989565 TI - Genotyping of Canadian hepatitis C virus isolates by PCR. AB - We used PCR for hepatitis C virus (HCV) genotyping with type-specific primers from the core and NS5 genes. Type I was predominant in the general population (58% in blood donors) as well as in different risk groups, such as intravenous drug abusers (58%), blood transfusion recipients (64%), hemophiliacs (62%), and patients with HCV chronic liver disease (76%). Types II, III, and IV were less prevalent in Canada, being found in 10.92, 6.72, and 5.88% of the population, respectively. The type II core primer was not type specific and reacted with the majority of our type I HCV samples, suggesting a false-positive dual infection with two different genotypes (I and II). Digestion of these amplified type I and type II products with restriction endonuclease AccI proved to be very useful in the exclusion of false-positive dual type I and type II infections. PMID- 7989566 TI - Outbreak of Brucella melitensis among microbiology laboratory workers. AB - We report on an outbreak of laboratory-acquired brucellosis involving four technicians working at a microbiology laboratory. All cases occurred in a period of 4 months. Blood cultures and the Rose Bengal test were positive for Brucella spp. in all cases. Microagglutination was positive for Brucella spp. at titers of between 1/40 and 1/160. All patients were cured after treatment. PMID- 7989567 TI - Prosthetic hip joint infection due to Campylobacter fetus. PMID- 7989568 TI - PCR diagnosis of typhoid fever. PMID- 7989569 TI - The immortalized chondrocyte: art without sacrifice. PMID- 7989570 TI - Studies of serpins unfold at a feverish pace. PMID- 7989571 TI - A new beginning for estrogen physiology. PMID- 7989572 TI - Reversal of experimental autoimmune encephalomyelitis with a hydroxamate inhibitor of matrix metalloproteases. AB - Gelatinases, belonging to the matrix metalloproteases, contribute to tissue destruction in inflammatory demyelinating disorders of the central nervous system such as multiple sclerosis. We used experimental autoimmune encephalomyelitis (EAE) as an animal model to evaluate the effect of a hydroxamate matrix metalloprotease inhibitor (GM 6001) on inflammatory demyelination. A single dose of the inhibitor, given intraperitoneally, provided sufficient levels in the cerebrospinal fluid of animals with EAE to induce at least a partial inhibition of the gelatinase activity in the cerebrospinal fluid. When administered daily either from the time of disease induction or from the onset of clinical signs, GM 6001 suppressed the development or reversed clinical EAE in a dose-dependent way, respectively. Animals returned to the same clinical course as the nontreated group after cessation of treatment. Animals treated from the onset of clinical signs had normal permeability of the blood-brain barrier, compared with the enhanced permeability in nontreated animals. These results indicate that matrix metalloprotease inhibition can reverse ongoing EAE. This effect appears to be mediated mainly through restoration of the damaged blood-brain barrier in the inflammatory phase of the disease, since, the degree of demyelination and inflammation did not differ between the treatment groups. PMID- 7989573 TI - Increases of intracellular magnesium promote glycodeoxycholate-induced apoptosis in rat hepatocytes. AB - Retention of bile salts by the hepatocyte contributes to liver injury during cholestasis. Although cell injury can occur by one of two mechanisms, necrosis versus apoptosis, information is lacking regarding apoptosis as a mechanism of cell death by bile salts. Our aim was to determine if the bile salt glycodeoxycholate (GDC) induces apoptosis in rat hepatocytes. Morphologic assessment included electron microscopy and quantitation of nuclear fragmentation by fluorescent microscopy. Biochemical studies included measurements of DNA fragmentation, in vitro endonuclease activity, cytosolic free Ca2+ (Cai2+), and cytosolic free Mg2+ (Mgi2+). Morphologic studies demonstrated typical features of apoptosis in GDC (50 microM) treated cells. The "ladder pattern" of DNA fragmentation was also present in DNA obtained from GDC-treated cells. In vitro endonuclease activity was 2.5-fold greater with Mg2+ than Ca2+. Although basal Cai2+ values did not change after addition of GDC, Mgi2+ increased twofold. Incubation of cells in an Mg(2+)-free medium prevented the rise in Mgi2+ and reduced nuclear and DNA fragmentation. In conclusion, GDC induces apoptosis in hepatocytes by a mechanism promoted by increases of Mgi2+ with stimulation of Mg(2+)-dependent endonucleases. These data suggest for the first time that changes of Mgi2+ may participate in the program of cellular events culminating in apoptosis. PMID- 7989574 TI - Induction of manganese superoxide dismutase in rat cardiac myocytes increases tolerance to hypoxia 24 hours after preconditioning. AB - Manganese superoxide dismutase (Mn-SOD) is induced in ischemic hearts 24 h after ischemic preconditioning, when tolerance to ischemia is acquired. We examined the relationship between Mn-SOD induction and the protective effect of preconditioning using cultured rat cardiac myocytes. Exposure of cardiac myocytes to brief hypoxia (1 h) decreased creatine kinase release induced by sustained hypoxia (3 h) that follows when the sustained hypoxia was applied 24 h after hypoxic preconditioning (57% of that in cells without preconditioning). The activity and content of Mn-SOD in cardiac myocytes were increased 24 h after hypoxic preconditioning (activity, 170%; content, 139% compared with cells without preconditioning) coincidentally with the acquisition of tolerance to hypoxia. Mn-SOD mRNA was also increased 20-40 min after preconditioning. Antisense oligodeoxyribonucleotides corresponding to the initiation site of Mn SOD translation inhibited the increases in the Mn-SOD content and activity and abolished the expected decrease in creatine kinase release induced by sustained hypoxia after 24 h of hypoxic preconditioning. Sense oligodeoxyribonucleotides did not abolish either Mn-SOD induction or tolerance to hypoxia. These results suggest that the induction of Mn-SOD in myocytes by preconditioning plays a pivotal role in the acquisition of tolerance to ischemia at a later phase (24 h) of ischemic preconditioning. PMID- 7989575 TI - A common cold virus, rhinovirus 16, potentiates airway inflammation after segmental antigen bronchoprovocation in allergic subjects. AB - Many patients with asthma have increased wheezing with colds. We hypothesized that rhinovirus colds might increase asthma by augmenting airway allergic responses (histamine release and eosinophil influx) after antigen challenge. Seven allergic rhinitis patients and five normal volunteers were infected with rhinovirus type 16 (RV16) and evaluated by segmental bronchoprovocation and bronchoalveolar lavage. Segmental challenge with saline and antigen was performed 1 mo before infection, during the acute infection, and 1 mo after infection. Lavage was performed immediately and 48 h after antigen challenge. Data were analyzed by two-way analysis of variance, and a P value of < or = 0.05 was considered to be significant. All volunteers inoculated with RV16 developed an acute respiratory infection. BAL fluid obtained from allergic rhinitis subjects during the acute viral infection, and 1 mo after infection, showed the following significant RV16-associated changes after antigen challenge: (a) an enhanced release of histamine immediately after local antigen challenge; (b) persistent histamine leak 48 h afterwards; and (c) a greater recruitment of eosinophils to the airway 48 h after challenge. These changes were not seen in non-allergic volunteers infected with RV16 and challenged with antigen, nor in allergic volunteers repetitively challenged with antigen but not infected with RV16, nor in RV16 infected allergic volunteers sham challenged with saline. We conclude that rhinovirus upper respiratory infection significantly augments immediate and late allergic responses in the airways of allergic individuals after local antigen challenge. These data suggest that one mechanism of increased asthma during a cold is an accentuation of allergic responses in the airway which may then contribute to bronchial inflammation. PMID- 7989576 TI - Endotoxin administration to humans inhibits hepatic cytochrome P450-mediated drug metabolism. AB - In experimental animals, injection of gram-negative endotoxin (LPS) decreases hepatic cytochrome P450-mediated drug metabolism. To evaluate this phenomenon in a human model of gram-negative sepsis, LPS was administered on two consecutive days to healthy male volunteers during which time a cocktail of antipyrine (AP 250 mg), hexobarbital (HB-500 mg), and theophylline (TH-150 mg) was ingested and the apparent oral clearance of each drug determined. Each subject had a control drug clearance study with saline injections. In the first experiment, six subjects received the drug cocktail 0.5 h after the first dose of LPS. In the second experiment, another six subjects received the drug cocktail 0.5 h after the second dose of LPS. In both experiments, LPS caused the expected physiologic responses of inflammation including fever with increases in serum concentrations of TNF alpha, IL-1 beta, IL-6, and acute phase reactants. In the first experiment, only minor decreases in clearances of the probe drugs were observed (7-12%). However in the second experiment, marked decreases in the clearances of AP (35, 95% CI 18-48%), HB (27, 95% CI 14-34%), and TH (22, 95% CI 12-32%) were seen. The decreases in AP clearance correlated with initial peak values of TNF alpha (r = 0.82) and IL-6 (r = 0.86). These data show that in humans the inflammatory response to even a very low dose of LPS significantly decreases hepatic cytochrome P450-mediated drug metabolism and this effect evolves over a 24-h period. It is likely that septic patients with much higher exposures to LPS have more profound inhibition of drug metabolism. PMID- 7989577 TI - Regulation of sterol carrier protein 2 (SCP2) gene expression in rat peritoneal macrophages during foam cell formation. A key role for free cholesterol content. AB - Sterol carrier protein 2 (SCP2) has been shown to be involved in intracellular transport and metabolism of cholesterol. However, there have been no reports concerning SCP2 in macrophages, the major source of atheromatous foam cells. We investigated whether SCP2 is present in rat peritoneal macrophages and determined the changes of SCP2 and its mRNA levels in macrophages during form cell formation induced by acetylated LDL (AcLDL). Immunoblot analysis and Northern blot analysis demonstrated that both SCP2 and its mRNA are expressed in rat peritoneal macrophages. Incubations with AcLDL caused a dose- and time-dependent increase of cellular esterified cholesterol, SCP2 and its mRNA in rat peritoneal macrophages. The inhibitor of acyl-CoA:cholesterol acyltransferase further enhanced AcLDL induced increase of SCP2 protein and its mRNA. Incubations with 25-hydroxy cholesterol also caused a dose-dependent stimulation of SCP2 gene expression in macrophages, while incubation with maleylated BSA had no effect. These results suggest that the increment of cellular-free cholesterol is responsible for enhanced SCP2 gene expression in macrophages. The enhancement of SCP2 gene expression by AcLDL suggests that SCP2 may play an important role during foam cell formation induced by AcLDL which may be most important step for the atherosclerosis. PMID- 7989579 TI - Production and characterization of transformed B-lymphocytes expressing the membrane defect of Scott syndrome. AB - Scott syndrome is a bleeding disorder associated with an isolated defect in expression of membrane coagulant activity by stimulated platelets. This defect represents a decrease in platelet membrane binding sites for coagulation factors Va and VIIIa, reflecting diminished surface exposure of phosphatidylserine (PS). To gain insight into the cellular and genetic basis for this disorder, B lymphocytes from a patient with Scott syndrome and from normal donors were immortalized by EBV-transformation, and tested for their capacity to expose plasma membrane PS in response to the Ca2+ ionophore, A23187. Upon incubation with A23187, EBV-lymphoblasts derived from normal donors consistently induced surface expression of PS in > 70% of all cells, as detected by membrane association of the PS-binding proteins, factor Va or annexin V. PS exposure in these cells was maximal after 5 min, and saturated at < 100 microM external free [Ca2+]. By contrast, < 30% of Scott syndrome lymphoblasts exposed PS, and saturation was not observed at > 1 mM external free [Ca2+]. Single-cell clones derived from the Scott lymphoblasts all exhibited a diminished response to A23187 comparable with that of the parental cells, suggesting that all lymphocytes from this patient share this membrane abnormality. Hybridomas prepared by fusion of Scott lymphoblasts with the myeloma cell line UC-LUC showed responses to Ca2+ ionophore comparable to those observed for normal lymphoblasts and for hybridomas prepared by fusion of normal lymphoblasts with UC-LUC. This correction of the Scott abnormality suggests possible complementation of an aberrant gene(s) responsible for this disorder. PMID- 7989578 TI - Rapid conversion to high xanthine oxidase activity in viable Kupffer cells during hypoxia. AB - It has been widely postulated that the central mechanism of hepatic reperfusion injury involves the conversion, during ischemia, of the enzyme xanthine dehydrogenase (XDH) to its free radical-producing form, xanthine oxidase (XOD). However, this theory has been questioned because (a) XDH to XOD conversion in whole liver occurs very slowly; (b) the cellular distribution of XDH/XOD is unclear; and (c) the direct demonstration of XDH to XOD conversion in viable cells is lacking. In this paper, we address all three issues by measuring XDH to XOD conversion and cell viability in purified populations of hepatic endothelial cells (EC), Kupffer cells (KC), and hepatocytes (HEP). Although XDH/XOD activity on a cellular basis was greater in hepatocytes (0.92 +/- 0.12 mU/10(6) cells) than ECs (0.03 +/- 0.01) or KCs (0.12 +/- 0.04), XDH + XOD specific activity was similar in all three cell types (HEP 1.85 +/- 0.10 U/g protein; EC 1.69 +/- 0.54; KC 2.30 +/- 0.22). Over 150 min of warm (37 degrees C) or 24 h of cold (4 degrees C) hypoxia, percent XOD activity increased slowly in ECs, from 21 +/- 2% (basal) to 39 +/- 3% (warm) and 49 +/- 5% (cold) and in HEPs (29 +/- 2% to 38 +/- 3% and 49 +/- 2%), but converted significantly faster in KCs (28 +/- 3% to 91 +/- 7% and 94 +/- 4%). The dramatic changes in Kupffer cell XOD during cold hypoxia occurred despite only minor changes in cell viability. When hypoxic KCs were reoxygenated after 16 h of cold hypoxia, there was a marked increase in cell death that was significantly blocked by allopurinol. These data suggest that significant conversion to the free radical-producing state occurs within viable KCs, and that Kupffer cell XOD may play an important role in mediating reperfusion injury in the liver. PMID- 7989580 TI - cAMP responsive element-mediated regulation of the gene transcription of the alpha 1B adrenergic receptor by thyrotropin. AB - To elucidate the molecular mechanism of the stimulatory effect of thyrotropin on the gene regulation of alpha 1B adrenergic receptor in functioning rat thyroid (FRTL-5) cells, we established a competitive reverse-transcriptase (RT) polymerase chain reaction (PCR) and nuclear run-off assay to quantify changes in mRNA levels and transcription rates. A binding assay showed that FRTL-5 cells predominantly expressed alpha 1B adrenergic receptor and that thyrotropin increased its expression sevenfold. By means of RT-PCR, we found that thyrotropin induced an 11-fold increase in alpha 1B receptor mRNA abundance. The nuclear run off assay demonstrated that thyrotropin caused a ninefold increase at the gene transcriptional level, which occurred in the presence of the protein synthesis inhibitor cycloheximide. The half-life of the alpha 1B receptor mRNA in cells incubated with thyrotropin for 1 h increased 1.5-fold but returned to the original value after 12 h. Dibutyryl cAMP and forskolin mimicked the stimulatory effects of thyrotropin on the gene transcriptional level. The 5'-flanking region of the rat alpha 1B receptor gene contained a putative cAMP responsive element (CRE) at nucleotide -438 relative to the translation start site. The promoter analysis using the reporter gene indicated that the CRE motif confers the cAMP sensitivity to the transcription of the rat alpha 1B receptor gene. These results demonstrated that a CRE-mediated mechanism is involved in the transcriptional regulation of the alpha 1B receptor gene by thyrotropin without requiring new protein synthesis. PMID- 7989581 TI - Sepsis stimulates nonlysosomal, energy-dependent proteolysis and increases ubiquitin mRNA levels in rat skeletal muscle. AB - We tested the role of different intracellular proteolytic pathways in sepsis induced muscle proteolysis. Sepsis was induced in rats by cecal ligation and puncture; controls were sham operated. Total and myofibrillar proteolysis was determined in incubated extensor digitorum longus muscles as release of tyrosine and 3-methylhistidine, respectively. Lysosomal proteolysis was assessed by using the lysosomotropic agents NH4Cl, chloroquine, leupeptin, and methylamine. Ca(2+) dependent proteolysis was determined in the absence or presence of Ca2+ or by blocking the Ca(2+)-dependent proteases calpain I and II. Energy-dependent proteolysis was determined in muscles depleted of ATP by 2-deoxyglucose and 2.4 dinitrophenol. Muscle ubiquitin mRNA and the concentrations of free and conjugated ubiquitin were determined by Northern and Western blots, respectively, to assess the role of the ATP-ubiquitin-dependent proteolytic pathway. Total and myofibrillar protein breakdown was increased during sepsis by 50 and 440%, respectively. Lysosomal and Ca(2+)-dependent proteolysis was similar in control and septic rats. In contrast, energy-dependent total and myofibrillar protein breakdown was increased by 172% and more than fourfold, respectively, in septic muscle. Ubiquitin mRNA was increased severalfold in septic muscle. The results suggest that the increase in muscle proteolysis during sepsis is due to an increase in nonlysosomal energy-dependent protein breakdown, which may involve the ubiquitin system. PMID- 7989582 TI - Thromboembolic disease due to thermolabile conformational changes of antithrombin Rouen-VI (187 Asn-->Asp) AB - A new variant of antithrombin (Rouen-VI, 187 Asn-->Asp) with increased heparin affinity was shown to have normal inhibitory activity which decreased slowly at 4 degrees C and rapidly at 41 degrees C. On electrophoresis the freshly isolated variant had an anodal shift relative to native antithrombin due to the mutation. A further anodal transition occurred after either prolonged storage at 4 degrees C or incubation at 41 degrees C due to the formation of a new inactive uncleaved component with properties characteristic of L-form (latent) antithrombin. At the same time, polymerization also occurred with a predominance of di-, tri-, and tetra-mers. These findings fit with the observed mutation of the conserved asparagine (187) in the F-helix destabilizing the underlying A-sheet of the molecule. Evidence of A-sheet perturbation is provided by the increased rate of peptide insertion into the A-sheet and by the decreased vulnerability of the reactive loop to proteolysis. The spontaneous formation of both L-antithrombin and polymers is consistent with our crystal structure of intact antithrombin where L-form and active antithrombin are linked together as dimers. The nature of this linkage favors a mechanism of polymerization whereby the opening of the A sheet, to give incorporation of the reactive center loop, is accompanied by the bonding of the loop of one molecule to the C-sheet of the next. The accelerated lability of antithrombin Rouen-VI at 41 versus 37 degrees C provides an explanation for the clinical observation that episodes of thrombosis were preceded by unrelated pyrexias. PMID- 7989583 TI - Growth inhibition of the intestinal parasite Giardia lamblia by a dietary lectin is associated with arrest of the cell cycle. AB - Giardia lamblia, a cause of diarrheal disease throughout the world, is a protozoan parasite that thrives in the small intestine. It is shown here that wheat germ agglutinin (WGA), a naturally occurring lectin widely consumed in normal human diets, reversibly inhibits the growth of G. lamblia trophozoites in vitro, and reduces infection by G. muris in the adult mouse model of giardiasis. The inhibitory effect was dose related, not associated with cytotoxicity and reversed by N-acetyl-D-glucosamine in accordance with the known specificity of the lectin and in agreement with the presence of GlcNAc residues on the surface membrane of G. lamblia trophozoites. Cell cycle analysis revealed that parasites grown in the presence of WGA are arrested in the G2/M phase, providing an explanation for the lectin-induced inhibition of cell proliferation. Comparison of electrophoretic profiles by lectin blot analysis revealed both glycoprotein induction and suppression in growth-arrested organisms. Our findings raise the possibility that blocking trophozoite growth with naturally occurring dietary lectins may influence the course of giardiasis. In addition, the study of cell cycle arrest by WGA may provide a model to study the regulation of cell division in lower eukaryotes. PMID- 7989584 TI - Activation of potassium channels contributes to hypoxic injury in proximal tubules. AB - The mechanisms responsible for the loss of cell potassium during renal ischemia are poorly understood. The present studies examined the hypothesis that potassium channels are activated as an early response to hypoxia and contribute to potassium loss independent from an inhibition of active K+ uptake. Potassium flux in suspensions of freshly isolated rat proximal tubules was measured using an ion selective electrode. Exposure of the tubules to hypoxia for only 2.5 min resulted in a rise in the passive leak rate of K+ but no decrease in active K+ uptake. The passive leak of K+ was associated with a 40% decrease in cell ATP content. The passive K+ efflux was inhibited by 5 mM Ba2+ (95%) and by 15 mM tetraethylammonium (85%) suggesting that K+ channels were the primary route of K+ movement. The effects of K+ channel blockade on the development of hypoxic injury were also examined. Tetraethylammonium and glibenclamide, an inhibitor of ATP sensitive K+ channels, reduced hypoxic injury as assessed by the release of lactate dehydrogenase or measurement of DNA damage. These results suggest that activation of K+ channels is an early response to hypoxia and contributes to hypoxic renal injury. PMID- 7989585 TI - Relation of pressor responsiveness to angiotensin II and insulin resistance in hypertension. AB - To test the hypothesis that the hypertension associated with insulin resistance is secondary to an altered responsiveness of the vasculature to pressor agents, we evaluated the relationship between insulin resistance and pressor responses to angiotensin II (AII) in 21 hypertensive (HT) and 8 normotensive (NT) subjects on both a high (200 meq) and a low (10 meq) sodium diet. When sodium balance was achieved, each supine fasting subject underwent an AII infusion at a rate of 3 ng/kg per min for 60 min, with blood pressure monitored every 2 min. On the next day under similar conditions, a euglycemic hyperinsulinemic clamp was performed, with plasma glucose clamped at 90 mg/dl for 120 min. There was no significant relationship between the glucose disposal rate (M) or the insulin sensitivity index (M divided by the mean insulin level [M/I]) and blood pressure response to AII in the NTs, but a highly significant (P < 0.019) negative correlation (r = 0.55) in the HTs. Furthermore, in eight lean HTs whose body mass index was identical to that observed in the NTs, the relationship was even more striking (P < 0.008; r = -0.85). The results on high and low salt diets were similar; however, the M and M/I were significantly increased (P < 0.05) in the NTs but not HTs with sodium restriction. In conclusion, HTs but not NTs display a striking correlation between pressor response to AII and insulin resistance. This relationship is independent of the level of sodium intake. Furthermore, sodium intake modifies insulin sensitivity in NTs but not HTs. These results strongly suggest that a primary change in pressor response to vasoactive agents in insulin resistant subjects can contribute to their elevated blood pressure. PMID- 7989586 TI - Interleukin-1 beta-modulated gene expression in immortalized human chondrocytes. AB - Immortalized human chondrocytes were established by transfection of primary cultures of juvenile costal chondrocytes with vectors encoding simian virus 40 large T antigen and selection in suspension culture over agarose. Stable cell lines were generated that exhibited chondrocyte morphology, continuous proliferative capacity (> 80 passages) in monolayer culture in serum-containing medium, and expression of mRNAs encoding chondrocyte-specific collagens II, IX, and XI and proteoglycans in an insulin-containing serum substitute. They did not express type X collagen or versican mRNA. These cells synthesized and secreted extracellular matrix molecules that were reactive with monoclonal antibodies against type II collagen, large proteoglycan (PG-H, aggrecan), and chondroitin-4- and chondroitin-6-sulfate. Interleukin-1 beta (IL-1 beta) decreased the levels of type II collagen mRNA and increased the levels of mRNAs for collagenase, stromelysin, and immediate early genes (egr-1, c-fos, c-jun, and jun-B). These cell lines also expressed reporter gene constructs containing regulatory sequences (-577/+3,428 bp) of the type II collagen gene (COL2A1) in transient transfection experiments, and IL-1 beta suppressed this expression by 50-80%. These results show that immortalized human chondrocytes displaying cartilage specific modulation by IL-1 beta can be used as a model for studying normal and pathological repair mechanisms. PMID- 7989587 TI - Disruption by interferon-alpha of an autocrine interleukin-6 growth loop in IL-6 dependent U266 myeloma cells by homologous and heterologous down-regulation of the IL-6 receptor alpha- and beta-chains. AB - IL-6 is an autocrine growth factor for U266 myeloma cells and their growth is inhibited by IFN-alpha or IL-6 mAb. We asked, therefore, whether IFN-alpha induced growth inhibition involved IL-6. IFN-alpha and mAb against IL-6, the IL 6R alpha-(gp80) or beta-chain (gp130) potently inhibited U266 cells. Remarkably, this effect occurred despite IFN-alpha-augmented secretion of endogenous IL-6. However, examining the IL-6R revealed that IFN-alpha drastically curtailed expression of the IL-6R alpha- and beta-chain. This effect occurred on two different levels (protein and mRNA) and by two different mechanisms (directly and indirectly through IL-6). First, IFN-alpha, but not IL-6, greatly decreased gp80 and, to a lesser extent, gp130 mRNA levels which resulted in a loss of IL-6 binding sites. Second, IFN-alpha-induced IL-6 predominantly down-regulated membrane-bound gp130. IFN-alpha-mediated decrease of gp80 levels was not detected on IL-6-independent myeloma (RPMI 8226) or myeloid cells (U937). We conclude that IFN-alpha inhibited IL-6-dependent myeloma cell growth by depriving U266 cells of an essential component of their autocrine growth loop, a functional IL-6R. PMID- 7989588 TI - The characterization of gene mutations for human glucose phosphate isomerase deficiency associated with chronic hemolytic anemia. AB - DNA was isolated from four unrelated glucose phosphate isomerase-deficient patients. Seven new mutations in the coding region were found: 247 C-->T, 671 C- >T, 818 G-->A, 833 C-->T, 1039 C-->T, 1459 C-->T, and 1483 G-->A. Three patients were compound heterozygotes, and one patient was a homozygote of 247 C-->T/247 C- >T. Six mutations were found to involve highly conserved amino acids of glucose phosphate isomerase, suggesting that these residues are crucial for the maintenance of biological activity. Two polymorphic sites were also identified, 489 A-->G and 1356 G-->C, which do not produce a change in the amino acid sequence. PMID- 7989589 TI - The role of lecithin: cholesterol acyltransferase for lipoprotein (a) assembly. Structural integrity of low density lipoproteins is a prerequisite for Lp(a) formation in human plasma. AB - The composition of lipoproteins in the plasma of patients with LCAT deficiency (LCAT-D) is grossly altered due to the lack of cholesteryl esters which form the core of normal lipoproteins. When plasma from LCAT-D patients and their relatives was examined we found that nine heterozygotes had plasma Lp(a) levels of 2-13 mg/dl whereas none of 11 affected homozygous individuals from different families contained detectable amounts of Lp(a) in their plasma. Therefore, the binding of apo(a) to LDL density particles was studied in vitro using LDL density fractions prepared from patients, and recombinant apo(a) [r-apo(a)], which was expressed and secreted by transfected COS-7 cells. The LDL from heterozygotes were chemically indistinguishable from normal LDL and homogeneous with regard to morphology, whereas the crude LDL floating fraction from homozygotes consisted of a heterogeneous mixture of large vesicles, and small spheres resembling normal LDL. The LDL density fraction from the LCAT-D patient lacked almost completely cholesteryl esters. Incubation of LCAT-D plasma with active LCAT caused a substantial augmentation of the original subfraction which morphologically resembled normal LDL. Using r-apo(a) and normal LDL or LDL of heterozygous individuals, apoB:r-apo(a) complexes were formed when incubated at 37 degrees C in vitro for 20 h. In contrast, the total LDL floating fraction from a homozygous LCAT-D patient failed to form apoB:r-apo(a) complexes. After treatment with active LCAT, a significant apoB:r-apo(a) association was observed with LCAT-D LDL density particles. Our data emphasize the importance of the integrity of LDL structure and composition for the formation of Lp(a). In addition, we demonstrate that the absence of LCAT activity has a fundamental impact on the regulation of plasma Lp(a) levels. PMID- 7989590 TI - Assessment of insulin action and glucose effectiveness in diabetic and nondiabetic humans. AB - Insulin concentrations in humans continuously change and typically increase only when glucose also increases such as with eating. In this setting, it is not known whether the severity of hepatic and extrahepatic insulin resistance is comparable and whether the ability of glucose to regulate its own uptake and release is defective in non-insulin-dependent diabetes mellitus (NIDDM). To address this question, NIDDM and nondiabetic subjects were studied when glucose concentrations were clamped at either 5 mM (euglycemia) or varied so as to mimic the glucose concentrations observed in nondiabetic humans after food ingestion (hyperglycemia). Insulin was infused so as to simulate a "nondiabetic" postprandial profile. During euglycemia, insulin increased glucose disposal in nondiabetic but not diabetic subjects indicating marked extrahepatic resistance. In contrast, insulin-induced suppression of glucose release was only minimally less (P < 0.05) in diabetic than nondiabetic subjects (-1.06 +/- 0.09 vs. -1.47 +/- 0.21 nmol.kg-1 per 4 h). Hyperglycemia substantially enhanced disposal in both groups. Glucose effectiveness measured as the magnitude of enhancement of disposal (0.59 +/- 0.18 vs. 0.62 +/- 0.17 nmollkg-1 per 4 h) and suppression of release (-0.36 +/- 0.12 vs. -0.14 +/- 0.12 nmol.kg-1 per 4 h) did not differ in the diabetic and nondiabetic subjects. In conclusion, when assessed in the presence of a physiological insulin profile, people with NIDDM demonstrate: (a) profound extrahepatic insulin resistance, (b) modest hepatic insulin resistance, and (c) normal ability of glucose to stimulate its own uptake and suppress its own release. PMID- 7989591 TI - Impaired free fatty acid utilization by skeletal muscle in non-insulin-dependent diabetes mellitus. AB - This study was undertaken to assess utilization of FFA by skeletal muscle in patients with non-insulin-dependent diabetes mellitus (NIDDM). 11 NIDDM and 9 nondiabetic subjects were studied using leg balance methods to measure the fractional extraction of [3H]oleate. Limb indirect calorimetry was used to estimate RQ. Percutaneous muscle biopsy samples of vastus lateralis were analyzed for muscle fiber type distribution, capillary density, and metabolic potential as reflected by measurements of the activity of seven muscle enzyme markers of glycolytic and aerobic-oxidative pathways. During postabsorptive conditions, fractional extraction of oleate across the leg was lower in NIDDM subjects (0.31 +/- 0.08 vs. 0.43 +/- 0.10, P < 0.01), and there was reduced oleate uptake across the leg (66 +/- 8 vs. 82 +/- 13 nmol/min, P < 0.01). Postabsorptive leg RQ was increased in NIDDM (0.85 +/- 0.03 vs. 0.77 +/- 0.02, P < 0.01), and rates of lipid oxidation by skeletal muscle were lower while glucose oxidation was increased (P < 0.05). In subjects with NIDDM, proportions of type I, IIa, and IIb fibers were 37 +/- 2, 37 +/- 6, and 26 +/- 5%, respectively, which did not differ from nondiabetics; and capillary density, glycolytic, and aerobic-oxidative potentials were similar. During 6 h after ingestion of a mixed meal, arterial FFA remained greater in NIDDM subjects. Therefore, despite persistent reduced fractional extraction of oleate across the leg in NIDDM (0.34 +/- 0.04 vs. 0.38 +/- 0.03, P < 0.05), rates of oleate uptake across the leg were greater in NIDDM (54 +/- 7 vs. 45 +/- 8 nmol/min, P < 0.01). In summary, during postabsorptive conditions there is reduced utilization of FFA by muscle, while during postprandial conditions there is impaired suppression of FFA uptake across the leg in NIDDM. During both fasting and postprandial conditions, NIDDM subjects have reduced rates of lipid oxidation by muscle. PMID- 7989592 TI - Glucocorticoid activation of chromogranin A gene expression. Identification and characterization of a novel glucocorticoid response element. AB - Glucocorticoids regulate catecholamine biosynthesis and storage at several sites. Chromogranin A, an abundant protein complexed with catecholamines in secretory vesicles of chromaffin cells and sympathetic axons, is also augmented by glucocorticoids. This study reports isolation of the rat chromogranin A promoter to elucidate transcriptional regulation of chromogranin A biosynthesis by glucocorticoids in neuroendocrine cells. Endogenous chromogranin A gene expression was activated up to 3.5-fold in chromaffin cells by glucocorticoid, in time-dependent fashion. Inhibition of new protein synthesis by cycloheximide did not alter the rise in chromogranin A mRNA, suggesting that glucocorticoids directly activate the chromogranin A promoter; nuclear runoff assays confirmed a 3.3-fold increased rate of initiation of new chromogranin A transcripts after glucocorticoid. Transfected rat chromogranin A promoter/luciferase reporter constructs were activated 2.6-3.1-fold by glucocorticoid, and selective agonist/antagonist studies determined that dexamethasone effects were mediated by glucocorticoid receptors. Both rat and mouse chromogranin A promoter/luciferase reporter constructs were activated by glucocorticoid. A series of promoter deletions narrowed the region of glucocorticoid action to a 93-bp section of the promoter, from position -526 to -619 bp upstream of the cap site. A 15-bp sequence ([-583 bp] 5'-ACATGAGTGTGTCCT-3' [-597 bp]) within this region showed partial homology to a glucocorticoid response element (GRE; half-site in italics) consensus sequence, and several lines of experimental evidence confirmed its function as a GRE: (a) site-directed mutation of this GRE prevented glucocorticoid activation of a chromogranin A promoter/reporter; (b) transfer of this GRE to a heterologous (thymidine kinase) promoter/reporter conferred activation by glucocorticoid, in copy number-dependent and orientation independent fashion; and (c) electrophoretic gel mobility shifts demonstrated binding of this GRE by ligand-activated glucocorticoid receptor, though at 2.75 fold lower affinity than the glucocorticoid receptor interaction with a consensus GRE. The rat chromogranin A GRE showed functional and structural similarities to GREs in other genes proportionally regulated by glucocorticoids. We conclude that a discrete domain of the chromogranin A promoter is both necessary and sufficient to confer glucocorticoid regulation onto the gene, and that the activity of this region also explains the degree of activation of the endogenous gene by glucocorticoid. PMID- 7989593 TI - 13C-nuclear magnetic resonance spectroscopy studies of hepatic glucose metabolism in normal subjects and subjects with insulin-dependent diabetes mellitus. AB - To determine the effect of insulin-dependent diabetes mellitus (IDDM) on rates and pathways of hepatic glycogen synthesis, as well as flux through hepatic pyruvate dehydrogenase, we used 13C-nuclear magnetic resonance spectroscopy to monitor the peak intensity of the C1 resonance of the glucosyl units of hepatic glycogen, in combination with acetaminophen to sample the hepatic UDP-glucose pool and phenylacetate to sample the hepatic glutamine pool, during a hyperglycemic-hyperinsulinemic clamp using [1-13C]-glucose. Five subjects with poorly controlled IDDM and six age-weight-matched control subjects were clamped at a mean plasma glucose concentration of approximately 9 mM and mean plasma insulin concentrations approximately 400 pM for 5 h. Rates of hepatic glycogen synthesis were similar in both groups (approximately 0.43 +/- 0.09 mumol/ml liver min). However, flux through the indirect pathway of glycogen synthesis (3 carbon units-->-->glycogen) was increased by approximately 50% (P < 0.05), whereas the relative contribution of pyruvate oxidation to TCA cycle flux was decreased by approximately 30% (P < 0.05) in the IDDM subjects compared to the control subjects. These studies demonstrate that patients with poorly controlled insulin dependent diabetes mellitus have augmented hepatic gluconeogenesis and relative decreased rates of hepatic pyruvate oxidation. These abnormalities are not immediately reversed by normalizing intraportal concentrations of glucose, insulin, and glucagon and may contribute to postprandial hyperglycemia. PMID- 7989594 TI - Variation at the hepatic lipase and apolipoprotein AI/CIII/AIV loci is a major cause of genetically determined variation in plasma HDL cholesterol levels. AB - Genetic factors have been shown to play an important role in determining interindividual variation in plasma HDL-C levels, but the specific genetic determinants of HDL cholesterol (HDL-C) levels have not been elucidated. In this study, the effects of variation in the genomic regions encoding hepatic lipase, apolipoprotein AI/CIII/AIV, and the cholesteryl ester transfer protein on plasma HDL-C levels were examined in 73 normotriglyceridemic, Caucasian nuclear families. Genetic factors accounted for 56.5 +/- 13% of the interindividual variation in plasma HDL-C levels. For each candidate gene, adjusted plasma HDL-C levels of sibling pairs who shared zero, one, or two parental alleles identical by-descent were compared using sibling-pair linkage analysis. Allelic variation in the genes encoding hepatic lipase and apolipoprotein AI/CIII/AIV accounted for 25 and 22%, respectively, of the total interindividual variation in plasma HDL-C levels. In contrast, none of the variation in plasma HDL-C levels could be accounted for by allelic variation in the cholesteryl ester transfer protein. These findings indicate that a major fraction of the genetically determined variation in plasma HDL-C levels is conferred by allelic variation at the hepatic lipase and the apolipoprotein AI/CIII/AIV gene loci. PMID- 7989595 TI - Discrimination between Crigler-Najjar type I and II by expression of mutant bilirubin uridine diphosphate-glucuronosyltransferase. AB - Crigler-Najjar (CN) disease is classified into two subtypes, type I and II. The molecular basis for the difference between these types is not well understood. Several mutations in the bilirubin UDP-glucuronosyl-transferase (B-UGT) gene of six CN type I and two CN type II patients were identified. Recombinant cDNAs containing these mutations were expressed in COS cells. B-UGT activity was measured using HPLC and the amount of expressed protein was quantitated using a sandwich ELISA. This enabled us to determine the specific activities of the expressed enzymes. All type I patients examined had mutations in the B-UGT1 gene that lead to completely inactive enzymes. The mutations in the B-UGT1 gene of patients with CN type II only partially inactivated the enzyme. At saturating concentrations of bilirubin (75 microM) CN type II patient A had 4.4 +/- 2% residual activity and CN type II patient B had 38 +/- 2% residual activity. Kinetic constants for the glucuronidation of bilirubin were determined. The affinities for bilirubin of B-UGT1 expressed in COS cells and B-UGT from human liver microsomes were similar with Km of 5.1 +/- 0.9 microM and 7.9 +/- 5.3 microM, respectively. B-UGT1 from patient B had a tenfold decreased affinity for bilirubin, Km = 56 +/- 23 microM. At physiological concentrations of bilirubin both type II patients will have a strongly reduced conjugation capacity, whereas type I patients have no B-UGT activity. We conclude that CN type I is caused by a complete absence of functional B-UGT and that in CN type II B-UGT activity is reduced. PMID- 7989597 TI - Quantitation of nitrotyrosine levels in lung sections of patients and animals with acute lung injury. AB - Activated alveolar macrophages and epithelial type II cells release both nitric oxide and superoxide which react at near diffusion-limited rate (6.7 x 10(9) M-1s 1) to form peroxynitrite, a potent oxidant capable of damaging the alveolar epithelium and pulmonary surfactant. Peroxynitrite, but not nitric oxide or superoxide, readily nitrates phenolic rings including tyrosine. We quantified the presence of nitrotyrosine in the lungs of patients with the adult respiratory distress syndrome (ARDS) and in the lungs of rats exposed to hyperoxia (100% O2 for 60 h) using quantitative immunofluorescence. Fresh frozen or paraffin embedded lung sections were incubated with a polyclonal antibody to nitrotyrosine, followed by goat anti-rabbit IgG coupled to rhodamine. Sections from patients with ARDS (n = 5), or from rats exposed to hyperoxia (n = 4), exhibited a twofold increase of specific binding over controls. This binding was blocked by the addition of an excess amount of nitrotyrosine and was absent when the nitrotyrosine antibody was replaced with nonimmune IgG. In additional experiments we demonstrated nitrotyrosine formation in rat lung sections incubated in vitro with peroxynitrite, but not nitric oxide or reactive oxygen species. These data suggest that toxic levels of peroxynitrite may be formed in the lungs of patients with acute lung injury. PMID- 7989596 TI - Interleukin-1 receptor antagonist and tumor necrosis factor binding protein decrease osteoclast formation and bone resorption in ovariectomized mice. AB - To investigate the contribution of IL-1, IL-6, and TNF to the increased osteoclastogenesis induced by estrogen deficiency, ovariectomized (ovx) mice were treated with either IL-1 receptor antagonist (IL-1ra), a competitive inhibitor of IL-1, TNF binding protein (TNFbp), an inhibitor of TNF, or the anti-IL-6 antibody (Ab) 20F3 for the first 2 wk after surgery. ovx increased the bone marrow cells secretion of IL-1 and TNF, but not IL-6, and the formation of TRAP-positive osteoclast-like multinucleated cells (MNCs) in bone marrow cultures treated with 1,25(OH)2D3. The increase in MNC formation induced by ovx was prevented by in vivo treatment with either 17 beta estradiol, IL-1ra, TNFbp, or anti-IL-6 Ab. However, the percent change in MNC formation induced by the anti-IL-6 Ab was similar in ovx and sham-operated animals, whereas IL-1ra and TNFbp were effective only in ovx mice. MNC formation was also decreased by in vitro treatment of bone marrow cultures with IL-1ra and TNFbp, but not with anti-IL-6 Ab. Ovx also increased bone resorption in vivo and in vitro, as assessed by the urinary excretion of pyridinoline cross links and the formation of resorption pits, respectively. IL-1ra, TNFbp and estrogen decreased bone resorption in vivo and in vitro whereas the anti-IL-6 Ab inhibited bone resorption in vitro but not in vivo. In conclusion, these data indicate that IL-1 and TNF play a direct role in mediating the effects of ovx on osteoclastogenesis and bone resorption. The data also suggest that IL-6 is not essential for increasing bone resorption in the early postovariectomy period. PMID- 7989598 TI - Experimental and/or genetically controlled alterations of the renal microsomal cytochrome P450 epoxygenase induce hypertension in rats fed a high salt diet. AB - Excess dietary salt induces a cytochrome P450 arachidonic acid epoxygenase isoform in rat kidneys (Capdevila, J. H., S. Wei, J. Yang, A. Karara, H. R. Jacobson, J. R. Falck, F. P. Guengerich, and R. N. Dubois. 1992. J. Biol. Chem. 267:21720-21726). Treatment of rats on a high salt diet with the epoxygenase inhibitor, clotrimazole, produces significant increases in mean arterial blood pressure (122 +/- 2 and 145 +/- 4 mmHg for salt and salt- and clotrimazole treated rats, respectively). The salt- and clotrimazole-dependent hypertension is accompanied by reductions in the urinary excretion of epoxygenase metabolites and by a selective inhibition of the renal microsomal epoxygenase reaction. The prohypertensive effects of clotrimazole are readily reversed when either the salt or clotrimazole treatment is discontinued. The indication that a salt-inducible renal epoxygenase protects against hypertension, are supported by studies with the Dahl rat model of genetic salt-sensitive hypertension. Dahl resistant animals responded to excess dietary salt by inducing the activity of their kidney microsomal epoxygenase(s) (0.102 +/- 0.01 and 0.240 +/- 0.04 nmol of products formed/min per mg of microsomal protein for control and salt-treated rats, respectively). Despite severe hypertension during excess dietary salt intake (200 +/- 20 mmHg), Dahl salt-sensitive rats demonstrated no increase in renal epoxygenase activity. These studies indicate that acquired or inherited abnormalities in renal epoxygenase activities and/or regulation can be related to salt-sensitive hypertension in rodents. Studies on the human renal epoxygenase and its relationship to salt hypertension may prove useful. PMID- 7989599 TI - Regulated expression of foreign genes in vivo after germline transfer. AB - Tight transcriptional control of foreign genes introduced into the germline of transgenic mice would be of great experimental value in studies of gene function. To develop a system in which the spatial and temporal expression of candidate genes implicated in cardiac development or function could be tightly controlled in vivo, we have generated transgenic mice expressing a tetracycline-controlled transactivator (tTA) under the control of a rat alpha myosin heavy chain promoter (MHC alpha-tTA mice), as well as mice harboring a candidate target gene implicated in the control of differentiation, Id1 (tet-Id1 mice). No expression of the target transgene was detected in any tissues of hemizygous tet-Id1 mice. Genetic crosses with MHC alpha-tTA mice resulted in transactivation of the Id1 transgene, but expression was restricted to heart, where tTA was expressed. Furthermore, transactivation of the target gene was tightly and reversibly controlled by systemic therapy with tetracycline, both in utero and postnatally. These studies demonstrate the feasibility of such a binary approach for tightly controlling the timing and extent of expression of transgenes in vivo. This approach should be generally useful for the ectopic expression of candidate genes in selected tissues during delineated developmental stages. PMID- 7989600 TI - Glucose regulation of hydroperoxide metabolism in rat intestinal cells. Stimulation of reduced nicotinamide adenine dinucleotide phosphate supply. AB - The regulation of intestinal metabolism of t-butylhydroperoxide by glucose was examined in isolated enterocytes from proximal rat intestine. The basal rate of hydroperoxide elimination in control cells was 0.57 +/- 0.05 nmol/min per 10(6) cells, and was increased threefold by 10 mM exogenous glucose (1.74 +/- 0.14 nmol/min per 10(6) cells). Concurrently, cellular NADPH levels increased threefold (1.62 +/- 0.40 nmol/10(6) cells vs 0.57 +/- 0.14 nmol/10(6) cells in controls). The glucose effect was blocked by 6-aminonicotinamide and by 1,3-bis (2-chloroethyl) 1-nitrosourea, consistent with glucose stimulation of NADPH production by the pentose phosphate shunt, and of NADPH utilization for glutathione disulfide reduction. The NADPH supply rate was quantified by controlled infusions of diamide, a thiol oxidant. At diamide infusion of 0.05 nmol/min per 10(6) cells, GSH and protein thiols in control cells were decreased significantly, consistent with a limited capacity for glutathione disulfide reduction. With glucose, cell GSH and protein thiols were preserved at a 10-fold higher diamide infusion which was reversed by 6-aminonicotinamide, supporting the view that glucose promotes glutathione disulfide reduction by increased NADPH supply. Collectively, the results demonstrate that intestinal metabolism of hydroperoxides subscribes to regulation by glucose availability. This responsiveness to glucose suggests that nutrient availability would be an important contributing factor in the detoxication of toxic hydroperoxides by the small intestine. PMID- 7989602 TI - Evidence for deactivation of both ectosolic and cytosolic 5'-nucleotidase by adenosine A1 receptor activation in the rat cardiomyocytes. AB - Adenosine, an important regulator of many cardiac functions, is produced by ectosolic and cytosolic 5'-nucleotidase. The activity of these enzymes is influenced by several ischemia-sensitive metabolic factors, e.g., ATP, ADP, H+, and inorganic phosphate. However, there is no clear evidence that adenosine itself affects 5'-nucleotidase activity. This study tested whether adenosine decreases the activity of ectosolic and cytosolic 5'-nucleotidase. Cardiomyocytes were isolated from adult male Wistar rats and suspended in the modified Hepes Tyrode buffer solution. After stabilization, isolated cardiomyocytes were incubated with and without adenosine (10(-9) - 10(-4) M). Ectosolic and cytosolic 5'-nucleotidase activity was decreased by exogenous adenosine (ectosolic 5' nucleotidase activity, 20.6 +/- 2.3 vs. 8.6 +/- 1.6 mumol/min per 10(6) cells [P < 0.05]; cytosolic 5'-nucleotidase activity, 2.47 +/- 0.58 vs. 1.61 +/- 0.54 mumol/min per 10(6) cells [P < 0.05] at 10(-6) M adenosine) after 30 min. The decrease in ectosolic and cytosolic 5'-nucleotidase activity was inhibited by 8 phenyltheophylline and pertussis toxin, and was mimicked by N6 cyclohexyladenosine, an adenosine A1 receptor agonist. Neither CGS21680C, and A2 receptor agonist, nor cycloheximide deactivated ectosolic and cytosolic 5' nucleotidase. Thus, we conclude that activation of adenosine A1 receptors is coupled to Gi proteins and attenuates ectosolic and cytosolic 5'-nucleotidase activity in rat cardiomyocytes. PMID- 7989601 TI - T cell cytokine responses in persons with tuberculosis and human immunodeficiency virus infection. AB - Tuberculosis causes more extensive and life-threatening disease in patients with HIV infection than in immunocompetent persons. To investigate the hypothesis that these severe manifestations of tuberculosis may be due to alterations in cytokine production, we evaluated cytokine patterns in HIV-infected tuberculosis patients. Upon stimulation with Mycobacterium tuberculosis in vitro, PBMC from HIV-infected tuberculosis patients had reduced proliferative and type 1 responses, compared with HIV-seronegative tuberculosis patients. The reduction in proliferative responses was independent of the CD4 cell count, but the reduced type 1 response was a direct result of CD4 cell depletion. There was no enhancement of type 2 cytokine production in HIV-infected patients, although production of IL-10 was prominent in all tuberculosis patients. In HIV-infected tuberculosis patients, M. tuberculosis-induced proliferative responses were significantly enhanced by neutralizing antibodies to IL-10 but not by antibodies to IL-4 or by recombinant IL-12. The M. tuberculosis-induced type 1 response was augmented both by antibodies to IL-10 and by recombinant IL-12. Tuberculosis in the context of HIV infection is characterized by diminished type 1 responses, probably induced by immunosuppressive cytokines produced by macrophages/monocytes, rather than by type 2 cells. PMID- 7989603 TI - Human ApoA-II inhibits the hydrolysis of HDL triglyceride and the decrease of HDL size induced by hypertriglyceridemia and cholesteryl ester transfer protein in transgenic mice. AB - The plasma cholesteryl ester transfer protein (CETP) mediates the exchange of HDL cholesteryl esters with triglycerides of other lipoproteins. Subsequent lipolysis of the triglyceride-enriched HDL by hepatic lipase leads to reductions of HDL size and apoA-I content. To investigate a possible modulation of the effects of CETP by apoA-II, human CETP transgenic mice were cross-bred with transgenic mice expressing human apoA-II and, in some cases, human apoA-I and apoC-III (with human-like HDL and hypertriglyceridemia). CETP expression resulted in reductions of HDL and increases in VLDL cholesteryl ester in mice expressing human apoA-II, alone or in combination with apoA-I and apoC-III, indicating that apoA-II does not inhibit the cholesteryl ester transfer activity of CETP. However, CETP expression resulted in more prominent increases in HDL triglyceride in mice expressing both apoA-II and CETP, especially in CETP/apoA-II/apoAI-CIII transgenic mice. CETP expression caused dramatic reductions in HDL size and apoA I content in apoAI-CIII transgenic mice, but not in apoA-II/AI-CIII transgenic mice. HDL prepared from mice of various genotypes showed inhibition of emulsion based hepatic lipase activity in proportion to the apoA-II/apoA-I ratio of HDL. The presence of human apoA-II also inhibited mouse plasma hepatic lipase activity on HDL triglyceride. Thus, apoA-II does not inhibit the lipid transfer activity of CETP in vivo. However, coexpression of apoA-II with CETP results in HDL particles that are more triglyceride enriched and resistant to reductions in size and apoA-I content, reflecting inhibition of hepatic lipase by apoA-II. The inhibition of HDL remodeling by apoA-II could explain the relatively constant levels of HDL containing both apoA-I and apoA-II in human populations. PMID- 7989604 TI - N-acetylcysteine inhibits muscle fatigue in humans. AB - N-acetylcysteine (NAC) is a nonspecific antioxidant that selectively inhibits acute fatigue of rodent skeletal muscle stimulated at low (but not high) tetanic frequencies and that decreases contractile function of unfatigued muscle in a dose-dependent manner. The present experiments test the hypothesis that NAC pretreatment can inhibit acute muscular fatigue in humans. Healthy volunteers were studied on two occasions each. Subjects were pretreated with NAC 150 mg/kg or 5% dextrose in water by intravenous infusion. The subject then sat in a chair with surface electrodes positioned over the motor point of tibialis anterior, an ankle dorsiflexor of mixed-fiber composition. The muscle was stimulated to contract electrically (40-55 mA, 0.2-ms pulses) and force production was measured. Function of the unfatigued muscle was assessed by measuring the forces produced during maximal voluntary contractions (MVC) of ankle dorsiflexor muscle groups and during electrical stimulation of tibialis anterior at 1, 10, 20, 40, 80, and 120 Hz (protocol 1). Fatigue was produced using repetitive tetanic stimulations at 10 Hz (protocol 1) or 40 Hz (protocol 2); intermittent stimulations subsequently were used to monitor recovery from fatigue. The contralateral leg then was studied using the same protocol. Pretreatment with NAC did not alter the function of unfatigued muscle; MVC performance and the force frequency relationship of tibialis anterior were unchanged. During fatiguing contractions stimulated at 10 Hz, NAC increased force output by approximately 15% (P < 0.0001), an effect that was evident after 3 min of repetitive contraction (P < 0.0125) and persisted throughout the 30-min protocol. NAC had no effect on fatigue induced using 40 Hz stimuli or on recovery from fatigue. N-acetylcysteine pretreatment can improve performance of human limb muscle during fatiguing exercise, suggesting that oxidative stress plays a causal role in the fatigue process and identifying antioxidant therapy as a novel intervention that may be useful clinically. PMID- 7989605 TI - Estrogen levels in childhood determined by an ultrasensitive recombinant cell bioassay. AB - We hypothesized that estradiol levels are higher in prepubertal girls than in prepubertal boys and that this greater secretion of estradiol might drive the more rapid epiphyseal development and earlier puberty in girls. Since previous estradiol assays have lacked adequate sensitivity to test the hypothesis of higher estradiol levels in girls, we developed a new ultrasensitive assay to measure estrogen levels. The assay uses a strain of Saccharomyces cerevisiae genetically engineered for extreme sensitivity to estrogen. Yeast were transformed with plasmids encoding the human estrogen receptor and an estrogen responsive promoter fused to the structural gene for beta-galactosidase. Ether extracts of 0.8 ml of serum were incubated with yeast for 8 h and the beta galactosidase response was used to determine estrogen bioactivity relative to estradiol standards prepared in charcoal-stripped plasma. The assay was highly specific for estradiol with < 3% cross-reactivity with estrone, estriol, or estradiol metabolites. The detection limit was < 0.02 pg/ml estradiol equivalents (100-fold lower than existing assays). Using this assay, we measured estrogen levels in 23 prepubertal boys (9.4 +/- 2.0 yr) and 21 prepubertal girls (7.7 +/- 1.9 [SD] yr). The estrogen level in girls, 0.6 +/- 0.6 pg/ml estradiol equivalents, was significantly greater than the level in boys, 0.08 +/- 0.2 pg/ml estradiol equivalents (P < 0.05). We conclude that the ultrasensitive recombinant cell bioassay for estrogen is approximately 100-fold more sensitive than previous estradiol assays, that estrogen levels are much lower prepubertally, in both sexes, than reported previously, and that prepubertal girls have 8-fold higher estrogen levels than prepubertal boys. PMID- 7989606 TI - Coexpression of the collagen-binding stress protein HSP47 gene and the alpha 1(I) and alpha 1(III) collagen genes in carbon tetrachloride-induced rat liver fibrosis. AB - HSP47 is a collagen-binding stress protein and is assumed to act as a collagen specific molecular chaperone during the biosynthesis and secretion of procollagen in the living cell. The synthesis of HSP47 has been reported to correlate with that of collagen in several cell lines. We examined the expression of HSP47 mRNA during the progression of carbon tetrachloride (CCl4)-induced liver fibrosis in rats. Northern blot analysis revealed that the expression of HSP47 mRNA was markedly induced during the progression of fibrosis in parallel with alpha 1(I) and alpha 1(III) collagen mRNAs. By in situ hybridization, the distribution of HSP47 transcripts was similar to that of alpha 1(I) collagen and was observed only in cells lining collagen fibrils. These collagen-positive cells were confirmed to be Ito cells by immunohistochemistry for desmin. The absence of high levels of HSP47 mRNA in the liver of rats treated with only a single administration of CCl4 indicated that the induction of HSP47 mRNA was not due to the direct effect of CCl4 as a stressor, but was due to the progression of liver fibrosis. The function of HSP47 in liver fibrosis will also be discussed. PMID- 7989607 TI - Interleukin-10 modulates type I collagen and matrix metalloprotease gene expression in cultured human skin fibroblasts. AB - IL-10, originally isolated from mouse helper T cells, is a cytokine with regulatory functions on a number of interleukins. In this study we show that recombinant human IL-10 affects the expression of several genes involved in extracellular matrix synthesis and remodeling in human dermal fibroblast cultures. As judged by Northern blot analyses, type I collagen gene expression was downregulated, while collagenase and stromelysin gene expression were markedly enhanced by IL-10. No effect on tissue inhibitor of metalloproteases mRNA levels was noted. Transient transfections of skin fibroblasts with type I collagen promoter/chloramphenicol acetyl transferase reporter gene constructs showed downregulation by IL-10, suggesting inhibition at the transcriptional level. When compared with control cultures, incubation with IL-10 resulted in a decrease in immunostaining of fibroblast cultures with antibodies to human type I collagen. In contrast, immunostaining of such IL-10-treated cultures with antibodies to human collagenase resulted in an increase in immunostaining. This study suggests a role for IL-10 in the breakdown and remodeling of the extracellular matrix. PMID- 7989608 TI - Increased expression of matrix metalloproteinases and matrix degrading activity in vulnerable regions of human atherosclerotic plaques. AB - Dysregulated extracellular matrix (ECM) metabolism may contribute to vascular remodeling during the development and complication of human atherosclerotic lesions. We investigated the expression of matrix metalloproteinases (MMPs), a family of enzymes that degrade ECM components in human atherosclerotic plaques (n = 30) and in uninvolved arterial specimens (n = 11). We studied members of all three MMP classes (interstitial collagenase, MMP-1; gelatinases, MMP-2 and MMP-9; and stromelysin, MMP-3) and their endogenous inhibitors (TIMPs 1 and 2) by immunocytochemistry, zymography, and immunoprecipitation. Normal arteries stained uniformly for 72-kD gelatinase and TIMPs. In contrast, plaques' shoulders and regions of foam cell accumulation displayed locally increased expression of 92-kD gelatinase, stromelysin, and interstitial collagenase. However, the mere presence of MMP does not establish their catalytic capacity, as the zymogens lack activity, and TIMPs may block activated MMPs. All plaque extracts contained activated forms of gelatinases determined zymographically and by degradation of 3H-collagen type IV. To test directly whether atheromata actually contain active matrix-degrading enzymes in situ, we devised a method which allows the detection and microscopic localization of MMP enzymatic activity directly in tissue sections. In situ zymography revealed gelatinolytic and caseinolytic activity in frozen sections of atherosclerotic but not of uninvolved arterial tissues. The MMP inhibitors, EDTA and 1,10-phenanthroline, as well as recombinant TIMP-1, reduced these activities which colocalized with regions of increased immunoreactive MMP expression, i.e., the shoulders, core, and microvasculature of the plaques. Focal overexpression of activated MMP may promote destabilization and complication of atherosclerotic plaques and provide novel targets for therapeutic intervention. PMID- 7989610 TI - Nitric oxide release accounts for insulin's vascular effects in humans. AB - Insulin exerts effects on the vasculature that (a) may play a role in the regulation of blood pressure; and (b) by boosting its own delivery to target tissues, also have been proposed to play an integral part in its main action, the promotion of glucose disposal. To study the role of nitric oxide (NO) in the mediation of insulin's effects on the peripheral vasculature, NG-monomethyl-L arginine (L-NMMA), a specific inhibitor of the synthesis of endothelium-derived NO, was infused into the brachial arteries of healthy volunteers both before, and at the end of a 2-h hyperinsulinemic (6 pmol/kg per min) euglycemic clamp. L-NMMA (but not norepinephrine, an NO-independent vasoconstrictor) caused larger reductions in forearm blood flow during hyperinsulinemia than at baseline. Moreover, L-NMMA prevented insulin-induced vasodilation throughout the clamp. Prevention of vasodilation by L-NMMA led to significant increases in arterial pressure during insulin/glucose infusion but did not alter glucose uptake. These findings indicate that insulin's vasodilatory effects are mediated by stimulation of NO release, and that they play a role in the regulation of arterial pressure during physiologic hyperinsulinemia. Abnormalities in insulin-induced NO release could contribute to altered vascular function and hypertension in insulin resistant states. PMID- 7989609 TI - Cyclooxygenase-2 is associated with the macula densa of rat kidney and increases with salt restriction. AB - The kidney is a rich source of prostaglandins. These eicosanoids, formed by cyclooxygenase-dependent metabolism of arachidonic acid, are important physiologic mediators of renal glomerular hemodynamics and tubular sodium and water reabsorption. Two separate isoforms of cyclooxygenase (COX) have now been identified: constitutive COX-1, encoded by a 2.8-kb mRNA, and mitogen-activated COX-2, encoded by a 4.0-4.5-kb mRNA. COX-2 expression increases during development and inflammation, but, except for brain, constitutive expression is low. It has been generally accepted that physiologic renal production of prostaglandins is mediated by COX-1. However, in the absence of inflammation, low levels of COX-2 mRNA are also detectable in the kidney. To examine the role of COX-2 in the kidney and determine its intrarenal localization, we used a 1.3-kb cDNA probe specific for the 3' untranslated region of rat COX-2 and COX-2 specific antiserum. The COX-2-specific cDNA probe hybridized with a 4.4-kb transcript in total RNA from adult rat kidney. Immunoblots of microsomes isolated from kidney cortex and papilla indicated immunoreactive COX-2 in both locations. In situ hybridization and immunohistochemistry indicated that renal cortical COX 2 expression was localized to the macula densa of the juxtaglomerular apparatus and to adjacent epithelial cells of the cortical thick ascending limb of Henle. In addition, COX-2 immunoreactivity was detected in interstitial cells in the papilla. No COX-2 message or immunoreactive protein was detected in arterioles, glomeruli, or cortical or medullary collecting ducts. When animals were chronically sodium restricted, the level of COX-2 in the region of the macula densa increased threefold (from 0.86 +/- 0.08 to 2.52 +/- 0.43/mm2) and the total area of the COX-2 immunoreactive cells in cortex increased from 34 microns2/mm2 of cortex to 226 microns2/mm2 of cortex. The intrarenal distribution of COX-2 and its increased expression in response to sodium restriction suggest that in addition to its proposed role in inflammatory and growth responses, this enzyme may play an important role in the regulation of salt, volume, and blood pressure homeostasis. PMID- 7989611 TI - Immune-deficient mice develop typical atherosclerotic fatty streaks when fed an atherogenic diet. AB - Inbred strain C57BL/6J mice develop typical atherosclerotic fatty streaks in the aorta after 15 wk on a high fat, high cholesterol diet. To investigate the effects of the immune system on the development of fatty streaks in this model, C57BL/6J mice with a normal immune system were compared with C57BL/6J mice carrying mutations resulting in various immune deficiencies. These included mice with severe combined immune deficiency, athymic "nude" mice, class I MHC deficient mice, and class II MHC deficient mice. Despite similar lipoprotein profiles, lesion development in the immune compromised strains was similar to or increased compared with normal C57BL/6J mice. Class I MHC deficient mice demonstrated a threefold increase in lesion area (22,961 +/- 6,653 vs 8,868 +/- 1,817 microns2, P = 0.01). Immunohistochemical analysis of lesions showed characteristic features of atherosclerosis with vascular cell adhesion molecule-1 expression, immunoglobulin deposition, monocyte infiltration, and smooth muscle cell proliferation. These data indicate that the classical immune system, while not essential for atherosclerotic fatty streak development, may act to suppress the development of lesions. PMID- 7989612 TI - Identification of the same factor V gene mutation in 47 out of 50 thrombosis prone families with inherited resistance to activated protein C. AB - Resistance to activated protein C (APC) is the most prevalent inherited cause of venous thrombosis. The APC resistance phenotype is associated with a single point mutation in the factor V gene, changing Arg506 in the APC cleavage site to a Gln. We have investigated 50 Swedish families with inherited APC resistance for this mutation and found it to be present in 47 of them. Perfect cosegregation between a low APC ratio and the presence of mutation was seen in 40 families. In seven families, the co-segregation was not perfect as 12 out of 57 APC-resistant family members were found to lack the mutation. Moreover, in three families with APC resistance, the factor V gene mutation was not found, suggesting another still unidentified cause of inherited APC resistance. Of 308 investigated families members, 146 were normal, 144 heterozygotes, and 18 homozygotes for the factor V gene mutation and there were significant differences in thrombosis-free survival curves between these groups. By age 33 yr, 8% of normals, 20% of heterozygotes, and 40% of homozygotes had had manifestation of venous thrombosis. PMID- 7989613 TI - CDR3 sequence motifs shared by oligoclonal rheumatoid arthritis synovial T cells. Evidence for an antigen-driven response. AB - T lymphocytes reactive with as yet undefined joint-localized foreign or autoantigens may be important in the pathogenesis of RA. Molecular studies demonstrating skewed T cell antigen receptor (TCR) variable gene usage and selective expansion of particular T cell clones within the synovial compartment support this view. Based on our recent study documenting selective expansion of V beta 17+ T cells in RA, we have pursued the identification of T cells relevant to the disease process, in an informative patient, by combining molecular analysis of freshly explanted RA synovial tissue V beta 17 TCR transcripts with in vitro expansion of V beta 17+ synovial tissue T cell clones. Peripheral blood V beta 17 cDNA transcripts proved heterogeneous. In contrast, two closely related sequences, not found in the peripheral blood, dominated synovial tissue V beta 17 transcripts, suggesting selective localization and oligoclonal expansion at the site of pathology. CD4+, V beta 17+ synovial tissue-derived T cell clones, isolated and grown in vitro, were found to express TCR beta chain transcripts homologous to the dominant V beta 17 synovial tissue sequences. One clone shares with a dominant synovial tissue sequence a conserved cluster of 4/5 amino acids (IGQ-N) in the highly diverse antigen binding CDR3 region, suggesting that the T cells from which these transcripts derive may recognize the same antigen. These findings have permitted a complete characterization of the alpha/beta TCR expressed by putatively pathogenic T cell clones in RA. Functional analysis suggests that the conserved CDR3 sequence may confer specificity for, or restriction by, the MHC class II antigen, DR4. PMID- 7989614 TI - An in vitro study of oscillating instruments for root planing. AB - The objective of this in vitro study was to test PER-IO-TOR instruments on the Profin Directional System angle piece (Dentatus-Sweden), using extracted human teeth. In the 1st part of the study, 6 root surfaces were treated with the instruments TOR 1, TOR 2, TOR 3 and TOR 4. For comparison purposes, half the samples treated with each instrument were then subjected to further treatment with a Gracey curette. All samples were then examined by SEM. In the 2nd part of the study, 4 root surfaces were given standardized treatment with each PER-IO-TOR instrument and the amount of substance removed was determined with a mechanical profilometer. For this purpose, the treated root surface was scanned with a microneedle and the profile depth recorded. The study showed that the PER-IO-TOR instruments were efficient with respect to surface planning and protective abrasion. Instrument TOR 3 (spatula with eyelet) in particular yielded similar results to those obtained with a curette. The overall results confirm that the PER-IO-TOR instruments have similar planing properties to manual instruments, causing minimum abrasion from the root surface. They thus represent an alternative to manual instruments, not only in inaccessible areas but also on smooth tooth surfaces. PMID- 7989615 TI - Trypsin-like activity levels of Treponema denticola and Porphyromonas gingivalis in adults with periodontitis. AB - Treponema denticola (Td) and Porphyromonas gingivalis (Pg) are associated with human moderate and severe adult periodontal diseases. This study quantifies these two anaerobes and their trypsin-like (TL) activities in subgingival plaque collected from both clinically healthy and periodontally diseased sites of human periodontitis patients. Antigen levels of the microorganisms were determined by monoclonal antibodies and TL activities were measured by the fluorescent substrate Z-gly-gly-arg-AFC in a disc format. Significant positive correlations were observed between the antigen levels and the TL activities when the data were subjected to statistical analyses both on a site-specific and on a patient basis. Anaerobe synergism was found between Td and Pg in a continental US population, and positive correlations were found between anaerobe levels (individually and total) and clinical indicators of adult periodontitis. PMID- 7989617 TI - Development of automated registration algorithms for subtraction radiography. AB - An algorithm is described which provides necessary information for automated registration and computation of alveolar height for subtraction radiographic analysis. This procedure involves identification of the cemento-enamel junctions from radiographic images by incrementally comparing a characteristic image signature along computed tooth boundaries. The identification of these anatomically invariant structures provides information necessary to warp images and create automatic superimposition, correcting for geometric misalignment. The present report describes and demonstrates the feasibility of utilizing automated CEJ, edge finding and image warping algorithms to align automatically sequential radiographs and permit their subtraction. PMID- 7989616 TI - Ex vivo studies of polymorphonuclear neutrophils from patients with early-onset periodontitis (II). Chemiluminescence response analysis. AB - Previous studies have indicated that oxygen-free radicals may cause damage to the periodontal tissues. This study compared the luminol-dependent chemiluminescence response (after stimulation with either opsonized zymosan or phorbol myristate acetate (PMA) of peripheral blood polymorphonuclear leukocytes (PMN) isolated from human subjects with a healthy periodontium (n = 7), gingivitis (n = 8), adult periodontitis (n = 8), or early-onset periodontitis (n = 17). These results were also compared with those obtained in a larger reference group which consists of 50 subjects without infection or inflammation, selected on the basis of laboratory investigations. An enhanced response was defined as being 2 standard deviations above the reference group mean; a reduced response was defined as being 2 standard deviations below this mean. Although PMN from patients with either gingivitis or periodontitis were often functionally activated (when compared to the PMN from the reference group), no significant differences could be found between the 4 groups, with regard to the chemiluminescence response means obtained in a basal state or after stimulation. PMID- 7989618 TI - The periodontal status of irregular dental attenders. AB - The aim of this investigation was to assess the prevalence and severity of periodontal destruction in irregular dental attenders. 50 subjects aged between 20 and 49 years completed a questionnaire and had a periodontal examination. Measurements of plaque, calculus, bleeding, probing depth and clinical attachment level were made at 4 proximal sites per tooth. Results were compared to those for 132 regular attenders. The irregular attenders had more sites with plaque (46.3 +/- 27% versus 17.3 +/- 21.1%) than the regulars and significantly more sites which bled (53.7 +/- 20.4% versus 33.6 +/- 20.7%) and with calculus (35 +/- 21.1% versus 13.4 +/- 12.8%). However, the irregulars had virtually the same number of teeth as the regular attenders, 25.6 +/- 3.3 compared with 25.4 +/- 4.3. Irregular attenders had slightly deeper mean probing depths (2.9 +/- 0.4 versus 2.7 +/- 0.4 mm) but the prevalence and extent of attachment loss was no different between the groups. It was concluded that the prevalence and severity of destructive periodontal disease as indicated by periodontal attachment loss was not related to the regularity of dental attendance in the groups studied. PMID- 7989619 TI - Experimental gingivitis during pregnancy and post-partum: clinical, endocrinological, and microbiological aspects. AB - The purpose of this study was to assess whether an intensive oral hygiene regimen practised during pregnancy results in a clinically healthy gingival state, and to assess whether experimentally-induced gingivitis differs in severity during pregnancy as compared to post-partum. In addition, levels of black-pigmented Gram negative anaerobes at subgingival and oral mucosal sites and plasma concentrations of free estrogens and prosterone were determined. These parameters were studied during a 14-day episode of experimental gingivitis induced in the 25th week of pregnancy, and again 6 months post-partum. The subjects were selected on shallow pockets < or = 4 mm and interproximal loss of attachment not exceeding 2 mm. As a result of controlled oral hygiene, the gingival condition improved both during pregnancy and post-partum. At day 0 during pregnancy, however, gingival swelling, redness, and bleeding on probing were found to be higher than post-partum. Free plasma levels of estrogens and progesterone were found to be normal throughout the study. It was hypothesized that the increase in severity of gingival symptoms during pregnancy reflect microvascular physiologic effects of increased levels of these hormones. During pregnancy, more swelling, redness and bleeding on probing developed during experimental gingivitis than post-partum, whereas the amount of plaque was similar in both phases. This suggests that as a result of dental plaque accumulation, gingival inflammation develops superimposed on pregnancy-associated physiologic alterations. Microbiological evaluation showed that the mean proportions of Prevotella intermedia in subgingival plaque increased during experimental gingivitis performed during pregnancy, whereas no increase of this micro-organism was found post-partum. PMID- 7989620 TI - Chronic lymphocytic leukaemia with gingival and palatal deposits. AB - The oral features of a patient with notable maxillary and mandibular gingival enlargement secondary to leukaemic infiltration in chronic lymphocyte leukaemia are presented. PMID- 7989621 TI - An evaluation of a pre-scaling gel (SofScale) on the ease of supragingival calculus removal. AB - SofScale is a pre-scaling gel, containing disodium EDTA and sodium lauryl sulphate, which is claimed to soften calculus and therefore facilitate its removal. 31 subjects were treated in a double blind randomised placebo controlled split mouth study to evaluate this product. Test or placebo gels were applied to the lingual surfaces of the mandibular teeth for 4 min and the time taken to complete the removal of supragingival calculus recorded. The operator recorded on which side the calculus was considered easier to remove and the patient indicated how comfortable the scaling had been. The mean calculus index was 1.99 for the SofScale group and 1.97 for the placebo. The mean time taken to complete scaling was 5.31 min for both groups. Using the Student t-test, there were no statistically significant differences (p > 0.7) between either the calculus index or time taken to complete the scaling between the groups. The operator did not consider SofScale to facilitate calculus removal and patients did not find calculus removal more comfortable when SofScale had been used. There was no increased sensitivity in the SofScale group following scaling. The results of this study do not support the use of SofScale as an adjunct to scaling. PMID- 7989622 TI - Serum fructosamine correlates with gingival index in children with insulin dependent diabetes mellitus (IDDM). AB - Fructosamine assay, which is used in diagnosing and monitoring diabetic patients, is compared with the hemoglobin and plasma glucose assays in children and adolescent insulin-dependent diabetes mellitus patients. We demonstrated that the gingival index scores were correlated with fructosamine values in insulin dependent diabetes mellitus patients but not in non-diabetic controls. We also found that there was no correlation between gingivitis scores and fasting plasma glucose and HbA1c values. Periodontitis was found to be rare in diabetic children and adolescents. PMID- 7989623 TI - And the children get poorer. PMID- 7989624 TI - Expanding the role of the health professional. PMID- 7989625 TI - Space maintainer cementation using light-hardened glass ionomer/resin restorative cement. PMID- 7989626 TI - Fevers in children. AB - Fever is one common reason that families seek medical or dental attention for a child. The fever reaction is a series of cellular events that begins peripherally and ends centrally with a resetting of the body's temperature set-point. The conditions that lead to the febrile reaction are many and include several oral etiologies. The health professional who initially evaluates the febrile child must use care in determining the cause, the severity, and the management of the patient's condition. In performing this task, one must consider the age of the child, the history of the illness, and the physical appearance of the patient. PMID- 7989627 TI - An in-vitro investigation of microleakage and gap size of glass ionomer/composite resin "sandwich" restorations in primary teeth. AB - Eighty extracted primary molars were divided into four groups of twenty teeth. Class II cavities were prepared in all teeth with equal numbers of proximal boxes having cavosurface margins either in enamel, or dentin/cementum. Each group was allocated to an open or closed sandwich technique using glass ionomer as a lining. Following the placement of the composite resin restorations, the gap size measured at the proximal box was greatest for the closed sandwich group with the cavosurface margin on enamel (0.203 microns) or dentin/cementum (0.174 microns). Microleakage scores were measured at the proximal box and were greatest for the closed sandwich group with the cavosurface margin on dentin/cementum. The best result was obtained for the open sandwich group with the cavosurface margin on enamel. PMID- 7989628 TI - The intraoral use of EMLA cream in children: a clinical investigation. AB - The use of 5 percent EMLA (an eutectic mixture of local anesthetics comprised of a mixture of prilocaine and lidocaine) as an intraoral topical anesthetic in children has been assessed in a clinical investigation. In a split-mouth study in twenty children there was no difference in the efficacy of EMLA and 5 percent lidocaine ointment in alleviating the pain of maxillary buccal infiltration injections of local anesthetics. EMLA did not differ significantly from placebo in the changes in pulpal responses of maxillary primary teeth to electrical stimulation before and after application in a double-blind split-mouth study in twenty children. PMID- 7989629 TI - Dental erosion in four-year-old children from differing socioeconomic backgrounds. AB - Although there is very little epidemiological evidence on the prevalence and severity of erosion in children and adults, there have been recent case reports suggesting that the problem of erosion is increasing. This study describes the use of a simple reproducible erosion index. A total of 178 four-year-old children were assessed; almost half of these children showed signs of erosion. The most common site affected was the palatal surface of the upper incisors with 17 percent of the children examined showing visible dentine for greater than one third of the tooth surface. When considering the influence of socioeconomic group on the prevalence of erosion, four out of five children examined in the low socioeconomic group showed low levels of erosion, while a much greater prevalence was observed in the higher socioeconomic groups. PMID- 7989630 TI - Predictors of dental anxiety in six-year-old children: findings from a pilot study. AB - The pilot study reported here is based on interviews with sixty, 6-year-old children randomly selected from a school population (and their mothers), to investigate predictors of dental anxiety in this age-group. The results demonstrated that child dental anxiety status was significantly related to dental factors, psychological developmental factors, and maternal factors. When all sixty data sets were entered into a regression analysis, 92 percent of the variance of the relationship of child dental anxiety could be predicted by eight factors in the three categories (F = 7.39, P < 0.001). The study demonstrated that the child's ability to cope with dental treatment (as reflected in reported disruptive behaviors) was based upon his/her degree of psychological development together with the mother's fear of dental treatment. It seems that an interaction exists, in which the role of the mother plays a central part influencing on the one hand the child's degree of psychological development and on the other the child's ability to cope with dental treatment. The findings from this preliminary study suggest that factors such as these should be considered by dentists when assessing their child patients, in order to identify and help the anxious child cope with dental care. PMID- 7989631 TI - Hypnosis as an adjunct to the administration of local anesthetic in pediatric patients. AB - This study investigates the acceptance of local anesthetic injection, utilizing hypnosis in twenty-nine children, ages four to thirteen years. Each subject was evaluated twice, once utilizing hypnosis before injection, and once without. A double blind research design was used to avoid effects of expectancy. Subjects in the study were videotaped during the procedure. Their behavior was rated independently by two pediatric dentists, using the North Carolina Behavior Rating Scale (NBRS). Transcutaneous pulse oximetry data were also recorded for each subject. The resulting data were evaluated for statistically significant differences between the two methods and for interrater reliability. Results showed no statistically significant differences in oxygen saturation due to hypnosis condition, order of treatment, sex, race, or age. Statistically significant differences were found in pulse rate and behavior, attributable to hypnosis condition and age, but not to sex, race, or order of treatment. Pulse rate decreased with hypnosis, as did crying. The hypnosis condition seemed to be more successful with younger children (four to six years old). PMID- 7989633 TI - Dentists' perceptions of the variety of dental services provided for children. AB - The purpose of this project was to describe the variety of dental services provided to child patients by general dentists and pediatric dentists. A survey was mailed to a random sample of 2000 general dentists and 1000 pediatric dentists requesting information about the dental services provided to children. Six hundred sixty-two general dentists (33 percent) and 492 pediatric dentists (49 percent) responded. Pediatric dentists reported more frequently obtaining informed consent (p < .0001), placing strip crowns (p < .0001), steel crowns (p < .0001) and pulp treatment procedures (p < .0001). Sealant use in both groups was high but the general dentists reported more frequently sealing occlusal surfaces with incipient caries (p < .001). There were differences in the reported provision of orthodontic services. The general dentists were more likely to refer children for treatment while the pediatric dentists reported they performed limited or comprehensive orthodontic treatment (p < .0001). The results of the survey demonstrate that pediatric dentists perceive that they provide a broader scope of restorative and orthodontic services. PMID- 7989632 TI - Comparison of the sedative effectiveness of two pharmacological regimens. AB - This study was designed to evaluate the effectiveness of two orally administered pharmacological regimens. The subjects were twenty-six patients requiring a sedative premedication for dental treatment, due to difficult behavior. A randomized, double-blind, cross-over design was employed using chloral hydrate syrup, 30 mg/Kg; and diphenhydramine HCl, 1.5 mg/Kg orally, not to exceed 2,000mg and 75mg, respectively; and chloral hydrate syrup, 30 mg/Kg; and diazepam solution, 0.2 mg/Kg orally, not to exceed 2000mg and 10mg, respectively. The level of conscious sedation was assessed, utilizing two scales employed previously in other studies. It was demonstrated that it is possible to maintain a low-dose range of sedative medication with satisfactory results. The combination of diazepam and chloral hydrate was found to be more effective than the diphenhydramine, chloral hydrate combination. PMID- 7989634 TI - Mom is out working: who is taking care of the kids? AB - A review is provided of the variety of child care arrangements that increasingly are being used by employed women. The potential impact on pediatric practices is considered. PMID- 7989635 TI - Children in rural areas: extending the horizons of pediatric dental practice. PMID- 7989637 TI - Improvement in major depression after low subcutaneous doses of MIF-1. AB - In this double-blind pilot study, 20 significantly depressed patients who all met the DSM-III R criteria for major depression were given a single subcutaneous injection of either 10 mg MIF-1 (Pro-Leu-Gly-NH2) or placebo on each of 5 consecutive days. Treatments were reversed for a second week of 5 consecutive daily injections. At the end of the first week, the group receiving MIF-1 was significantly improved on all rating scales as compared with the group receiving placebo. Eight out of 9 patients receiving MIF-1 showed marked improvement (score < or = 7 on the Hamilton Scale) as compared with only 2 of 11 patients receiving saline (P < 0.01). Administration of MIF-1 during the second week to the patients who had received placebo during the first week resulted in substantial improvement so that by the end of the second week the two groups were indistinguishable. PMID- 7989636 TI - A study of baby bottle tooth decay and risk factors for 18-month old infants in rural Japan. AB - Caries risk factors in rural Japan were identified for 637 children age eighteen months. Oral examinations, behavioral risk questionnaires and caries activity tests (Cariostat) were utilized. Results indicated an overall 13.7 percent prevalence of decay and strong correlations between Cariostat and caries status. Of the behavioral risk factors, weaning from breast feeding was most closely related with caries status. All factors resulted in correct classifications of Cariostat score and caries status. These results suggest that a screening of high risk infants can be accomplished by using the questionnaire and Cariostat test. PMID- 7989638 TI - Predictors of (non-) response in depressed outpatients treated with a three-phase sequential medication strategy. AB - The predictive value of eight domains or sets of variables including sociodemographic aspects, premorbid history, symptomatology, personality, social and diagnostic data are evaluated in depressed outpatients with a Hamilton Rating Scale for Depression (HRSD) score of at least 14. Patients were treated using a three-phase sequential treatment strategy. Of the 119 patients, 88 completed the trial. The HRSD-score at the end of phases I, II or III was used as an outcome measure. Patients with an initially high HRSD-score and an obsessive-compulsive personality had a greater chance of recovery, while patients with somatization and a passive-aggressive personality had less of a chance of recovery. Variables involving psychiatric history, premorbid history or symptomatology of the depression, were not significantly related to outcome. The endogenous/non endogenous distinction was not a predictor of response. PMID- 7989639 TI - Psychopathology in families of children with major depressive disorders. AB - Family psychiatric histories of 63 inpatient children with major depressive disorder (MDD) and 63 matched inpatient psychiatric controls were compared. MDD, anxiety disorders, somatization disorder and antisocial personality disorder (ASP) were significantly more common (P < 0.05) in the family histories of MDD probands. When family histories of depressed/anxious (D/A) versus depressed/behavior disordered (D/B) children were compared, the D/B group had more alcohol abuse (P < 0.05) and antisocial personality disorder (P < 0.08) than the D/A group. This report supports findings from earlier studies and suggests mood and anxiety disorders are increased in families of children with MDD. PMID- 7989640 TI - What factors predict discrepancies between self and observer ratings of depression? AB - This study used a matched clinician and self-rating scale, the Inventory for Depressive Symptomatology (IDS; Rush et al., 1986), in the assessment of 48 patients meeting DSM-III-R criteria for non-psychotic major depressive disorder. Patients generally rated their symptoms as more severe than the clinician, but differences between the self and clinician rating (the delta-IDS) were significantly correlated with non-endogenous depressive subtype, higher levels of neuroticism and dysfunctional attitudes, and lower self-esteem. Multiple linear regression analysis which controlled for severity of depression demonstrated that whilst neuroticism, dysfunctional attitudes and self-esteem accounted for 48.5% of the variance in delta-IDS, the variable accounting for most of the variance was low self-esteem (47.9%). PMID- 7989641 TI - A longitudinal study of diurnal mood variation in depression; characteristics and significance. AB - The course of 39 depressed in-patients' daily mood was recorded by means of frequent self-ratings during their entire stay (in total 3718 days). The frequency of diurnal variations largely varies between subjects without clear dichotomy in 'diurnal' and 'non-diurnal' subjects and the occurrence of diurnal variations is rather irregular. Mood variability measures rather than average daily mood improvement correlate with the response to sleep deprivation. These observations do not support theories of chronobiological rhythm disturbances in depression. It is argued that depressed subjects largely vary in susceptibility to stimuli. Signals generated by the biological clock or by processes related to the sleep-wake cycle are considered examples of such stimuli. PMID- 7989642 TI - Mood congruent and incongruent psychotic depressions: are they the same? AB - DSM-III and DSM-III-R instruct the clinician, if possible, to classify major depression with psychotic features into either the mood congruent (MC) or mood incongruent (MI) subtype. Patients hospitalized on a psychiatric unit for major depression with psychotic features were classified as predominantly MC or MI. The MC and MI groups did not differ significantly on a number of demographic or symptom severity variables. Thirteen (50%) MI patients experienced at least one MC symptom and 10 (71%) MC patients experienced at least one MI symptom. Overall, 25 (58%) of these patients experienced both MC and MI symptoms. This study demonstrates that subtyping psychotic depression into MC and MI subtypes is seldom an 'either-or' decision. Indeed, these results combined with findings from previous research suggests that there is no compelling scientific evidence for subclassifying psychotic depression into subtypes. PMID- 7989643 TI - The National Depressive and Manic-depressive Association (DMDA) survey of bipolar members. AB - Members of the National Depressive and Manic-Depressive Association who have bipolar disorder were surveyed. 59% of respondents had their first symptoms during childhood or adolescence. Long delays between symptom onset, treatment seeking, and receipt of a bipolar diagnosis were common. 45% of respondents currently experience frequent recurrences. Child/adolescent onset was associated with a positive family history, depressive or mixed initial symptoms, and frequent recurrence, with predominantly depressive symptoms. Frequent recurrences were associated with depressive or mixed initial symptoms and depressive episodes, but not with medication non-compliance. Both child/adolescent onset and frequent recurrence were associated with increased social morbidity, which was diminished by effective treatment. Respondents with frequent recurrences were less likely to be treated with mood-stabilizers, more likely to be treated with anti-depressants, or anxiolytics, and more likely to report past anxiety symptoms and diagnoses. 13% of respondents had no medical insurance, and 15% had failed to take medicine for financial reasons. The treatment of bipolar illness could be enhanced by (a) public health efforts to promote early diagnosis and treatment; (b) ensuring adequate trials of mood-stabilizers for patients with frequent recurrences; (c) further research on bipolar disorder with prominent anxiety symptoms; and (c) improved access to mental health care. PMID- 7989644 TI - Thermal lens spectrometry in biochemical analysis. AB - The photothermal spectroscopic techniques, with special emphasis on the thermal lens spectrometry (TLS), are introduced to the non-specialist in laser spectroscopy. The following topics are treated on an elementary basis: fundamentals and analytical characteristics, instrumentation, selectivity and multi-wavelength capability, the models describing the signal-concentration relationship, the sensitivity, background noise and limits of detection, the influence of light scattering and flow. Applications related to the fields of clinical and biochemical analysis and organic pollution are given. The thermal lens circular dichroism and the infrared TLS are also briefly outlined. PMID- 7989645 TI - Multiphasic modelling of ligand/acceptor interactions. The hydrophobicity dependent binding of relatively small amphiphilic substances to acceptor proteins and the nature and facedness of acceptor sites. AB - The modelling of multiphasic ligand/acceptor equilibrium binding systems proceeds at three logically distinct levels: (1) A suitable response quantity, e.g. the amount of acceptor-bound ligand nEL, is expressed as a function of the ligand concentrations [Li] (L = A,B,...) in the compartment i that contains the acceptor sites. One thus obtains a response function nEL = f1([Li]). In general, the equilibrium constants KL contained in such mathematical models are physically ill defined. (2) Each local concentration [Li] is further expressed as a function of [Laq], the corresponding concentration in the aqueous phase, leading to nEL = f2([Laq]). In this way, the constants KL are transformed into effective constants K'L which (i) can be assessed experimentally and (ii) depend on ligand hydrophobicity in a way that is characteristic of the binding site. Formulation of the functions f1 and F2 only requires knowledge of the reactions in which the acceptor sites participate directly. (3) For each ligand, the experimentally accessible total ligand concentration Lt is expressed as a function of [Laq], leading to concentration balance equations Lt = Lt([Laq]). The latter transformation takes account of any reactions, distinct from ligand/acceptor interaction, in which the ligands are involved, e.g. binding to additional protein sites. As a result of steps 2 and 3, each binding system is described by a set of simultaneous equations dependent on the auxiliary variable [Laq]: (i) the response function f2([Laq]) and (ii) a concentration balance for each ligand Lt = Lt([Laq]). The formulae are rendered more conscise and their discussion and application to data fitting are simplified by introducing, for each ligand L, a function FL characterising the distribution of unbound monomeric ligand over the various partition compartments. When the acceptor acts on unbound ligand, the formulae are further expressed in terms of a new auxiliary variable i.e. the total concentration of unbound monomeric ligand microL. In contrast to data analysis as a function of local concentrations, analysis in terms of total ligand concentrations avoids losing sight of alternate hypotheses about the nature of the binding sites. The present formulation has also permitted clarification of several consequences of the multiphasic nature of the binding systems that, as yet, have been poorly recognised.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 7989646 TI - Interaction of some anti-hypoxia drugs with hydroxypropyl-beta-cyclodextrin studied by means of charge transfer chromatography. AB - The interaction of 12 anti-hypoxia drugs with hydroxypropyl-beta-cyclodextrin (HPBCD) and the influence of LiCl, NaCl and KCl on the strength of interaction was studied by charge transfer chromatography. Most of the drugs form inclusion complexes with HPBCD and the relative strength of interaction varies markedly according to the structure of the drugs. Salts exert a considerable influence on the inclusion complex formation and the effect depends on the radii of the cation. The significant correlations between the lipophilicity of drugs and their capacity to form inclusion complexes with HPBCD indicate the involvement of hydrophobic forces in the interaction. PMID- 7989647 TI - Purification and characterization of the ecto-Mg-ATPase of chicken gizzard smooth muscle. AB - The ecto-Mg-ATPase isolated from chicken gizzard smooth muscle was solubilized, purified and characterized. The purification did not require the use of expensive or specialized apparatus. The chromatographic and electrophoretic characteristics of the ecto-Mg-ATPase from chicken are similar to those reported earlier for the ecto-Mg-ATPase isolated from rabbit skeletal muscle transverse tubule membranes [1992, J. Biol. Chem. 267, 11777-11782]. One obvious difference found was that the solubilized chicken ecto-Mg-ATPase can be stimulated approximately 1900% by the lectin Concanavalin A (Con A) under the same conditions that the rabbit enzyme is inhibited by approximately 50%. This stimulatory effect of Con A is useful for following the purification, and also increases the specific activity of the chicken enzyme to a very high level similar to that observed for the rabbit enzyme. After purification of the solubilized chicken ecto-Mg-ATPase by three steps of anion exchange chromatography, as well as Con A and erythroagglutinating Phaseolus vulgaris (PHA-E) lectin affinity chromatographies, a single diffuse glycoprotein band at approximately 66 kDa is observed after SDS PAGE. This protein could be deglycosylated to a core protein of 53 kDa. Thus, the chicken gizzard protein is very similar in molecular size to the rabbit skeletal muscle ecto-Mg-ATPase both before and after deglycosylation [1992, J. Biol. Chem. 267, 11777-11782]. The N-terminal sequence of the 66 kDa chicken gizzard protein was found to be: Ala-Arg-Arg-Ala-Ala-Ala-Val-Leu-Leu-Leu-Leu-Ala. This is a unique sequence which, while very different from the rabbit ecto-Mg-ATPase N terminus, exhibits some of the same characteristics, since it contains basic residues as the second and third amino acids, with the remainder of the N terminus being very hydrophobic in nature. Furthermore, the chicken gizzard ecto Mg-ATPase can be separated from the adhesion molecule, truncated cadherin (T cadherin) by anion exchange chromatography, and is therefore not identical to that protein, as had been recently proposed [1993, Arch. Biochem. Biophys. 303, 32-43]. PMID- 7989648 TI - Peroxide accumulation in detergents. AB - It is known that polyether detergents have a propensity for peroxide accumulation but the rate of this accumulation and the conditions under which it occurs are not well-appreciated. We here describe the use of the FOX (ferrous oxidation in Xylenol orange) assay as a screen for detergent peroxide accumulation. We also show that a chain-breaking antioxidant, but not a metal-chelating agent block peroxide accumulation in detergent stored in the light at room temperature. PMID- 7989649 TI - Selection and enrichment of differentially labeled plant protoplasts. AB - A fast and efficient method for the selection of plasmamembrane-marked protoplasts via magnetic-associated cell separation (MACS) was developed. Isolated mesophyll protoplasts from sunflower (Helianthus annuus L.) were covalently labeled at their plasma membrane with fluoresceine isothiocyanate (FITC) with an efficiency of greater than 95%. They were subsequently coupled to specific monoclonal antibodies against FITC, which were conjugated to magnetic beads, and mixed with unlabeled hypocotyl protoplasts. About 95% of the marked mesophyll protoplasts were separated by the MACS system with a purity of greater than 80%. Protoplasts embedded in agarose showed normal dividing activities. PMID- 7989650 TI - [Systematic search of the posterior vitreous cortex during vitrectomy. Technique, complications and results]. AB - We present the results of a prospective study trying to answer the question: when a clinical or echographic premacular vitreous detachment occurs, is it still possible to find a preretinal membrane at the surface of retina? We looked for such a membrane in 50 consecutive vitrectomies for various indications. We found and removed such a membrane in 42 cases but were unable to obtain histological examinations. Our conclusions are: most of the time, the diagnosis of total vitreous detachment is very difficult and the finding of a premacular membrane during vitrectomy is a frequent event. PMID- 7989651 TI - [Exfoliative syndrome and phacoemulsification]. AB - PURPOSE: Exfoliation syndrome (ES) is often considered as a poor indication for phacoemulsification because of zonular weakness, capsular weakness and poor pupil dilatation. METHODS: We evaluated from January 1992 to December 1992 a series of 107 consecutive eyes with ES and undergoing cataract surgery or combined cataract glaucoma surgery. The pupil was surgically enlarged if the diameter was < or = 5 mm. RESULTS: During surgery, only one case of zonular dialysis without vitreous loss was observed. The incidence of postoperative complications was low (6 hyphemas and 8 inflammatory reactions) and visual results were satisfactory. CONCLUSION: Phacoemulsification can be used routinely in eyes with ES if a careful peroperative protocol is followed: pupillary dilatation, wide capsulorhexis, total nucleus hydrodisection. PMID- 7989652 TI - [Should measurement of ocular tonus be repeated? Statistical analysis of 64 measurement in 25 patients]. AB - PURPOSE: This study aimed to determine usefulness of repeating tonometry and averaging of the results in order to increase precision. METHODS: Variance analysis was performed, the intra class correlation coefficient was calculated to determine the confidence intervals (95%) for averaging with two or more results. RESULTS: For one measurement the confidence interval was 7.07 mmHg, for 2 measurement, it was 5.00 mmHg and for 3 measurement 4.08 mmHg. For more measurements, there was little more improvement in precision. CONCLUSION: We therefore recommend to perform the tonometry twice, averaging the 2 results, in order to increase the precision of the final result. If more precision is required a third measurement and averaging of the 3 results can be made. Although it was proven that the influence of carefully repeated aplanation tonometry is not significant on the resultats for 2 or 3 measurements, averaging could be done during a single consultation. PMID- 7989653 TI - [Combined cataract-glaucoma operations. Extracapsular extraction and trabeculectomy versus phacoemulsification and trabeculectomy]. AB - This retrospective study was conducted to evaluate the results of Combined Surgery of Cataract and Glaucoma (triple procedure). The procedure of combined surgery were trabeculectomy and extracapsular extraction (14 eyes) versus trabeculectomy and phacoemulsification (15 eyes). The follow-up of both groups was at least 9 months and up to 16 months (mean: 12 months). The mean decrease of IOP was 12.4 mmHg and 8.9 mm Hg in the first and second group respectively. Instillation of Beta-blockers twelve months after surgery were more frequent in the first group (64.3%) than in the second (26.7%). Finally, the IOP values one year after surgery were equivalent in both groups (less than 19 mmHg in 93% of cases). The mean features to emphasize the delay of recuperation of the best corrected visual acuity: one month for phacotrabeculectomy, and three months for extracapsular with trabeculectomy. The frequency of complications was low in both groups. We observed more hyphemas but less secondary cataracts in the phacotrabeculectomy group. Phacotrabeculectomy could become a reference procedure for combined glaucoma and cataract surgery. PMID- 7989654 TI - [Madarosis and alopecia areata of eyelashes]. AB - We presented the clinical features of a 9-year-old girl and a 52-year-old man with alopecia areata of eyelashes. Alopecia areata refers to the idiopathic lesions of the eyelashes and is generally classified as being partial, total or universal. PMID- 7989655 TI - [Uveitis in juvenile chronic arthritis]. AB - The authors report the follow-up of thirty patients and 49 eyes, with uveitis associated to juvenile chronic arthritis. Clinical characteristics and risk factors of uveitis are: female gender (90%), bilateral involvement (63%), chronicity (91%), relapses (94%), oligoarticular arthritis (73%), antinuclear antibodies (83%). The intraocular inflammation was most frequently asymptomatic. It is extremely important to screen the patients systematically at regular intervals in order to early diagnose the uveitis to improve the visual prognosis. Risk factors for significant visual loss are still cataract (26.5%) and secondary glaucoma (10%). The most devastating complication is secondary glaucoma. PMID- 7989656 TI - [Orbital measurements in Zairian children. Inner canthal, outer orbital, inter pupillary distances and proptosis]. AB - Measurements of outer orbital distance, inner canthal distance and of interpupillary distance and proptosis were performed on 95 healthy Zairian subjects. The subjects were aged from 2 1/2 to 18 years. There were 47 boys (mean age +/- SD, 9.74 +/- 4.4 years) and 48 girls (mean age +/- SD, 9.07 +/- 4.1 years). No statistically significant difference was found between the two sexes for the mean age. Subjects were divided in four age groups: the first age group included children aged from 2 1/2 to 6 years (mean age +/- SD, 4.62 +/- 1.31 years), the second age group included children aged from 7 to 10 years (mean age, 8.32 +/- 1.22 years), the third included subjects aged from 11 to 14 years (mean age +/- SD, 12 +/- 1.06 years) and the fourth included subjects aged from 15 to 18 years (mean age +/- SD, 17 +/- 3 years). The measurements were performed with the Hertel exophthalmometer for the proptosis and the outer orbital distance, with the pupillometer model PD-2 meter for the interpupillary distance; with a ruler for the inner canthal distance. The mean +/- SD inner canthal was 27.4 +/- 2.7 mm for the first age group, 29.7 +/- 3.1 mm for the second age group, 30 +/- 2.4 mm for the third age group and 32.2 +/- 3.1 mm for the fourth age group. The mean +/- SD outer orbital was 100.0 +/- 4.4 mm for the first age group, 106.5 +/- 4.6 mm for the second age group, 111.7 +/- 6.8 mm for the third age group and 118.5 +/- 6.4 mm for the fourth age group.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7989657 TI - [Retinitis pigmentosa, vitiligo and deaf-mutism. Apropos of a case]. AB - The paper presents the observation of a 47 year-old patient with pigmentary retinopathy, hypoacousy, and vitiligo. The retinopathy and hypoacousy were associated in 10% of the cases. There is a certain parallelism between the degeneration of the retineal epithelium and the Corti neurosensorial epithelium. The association with vitiligo is only rarely mentioned in the literature. The extension of the abiotrophic process at the level of the cutaneous melanocytes may be explained by the variable expressivity of the pathological gene with the affection of different diencefalic nervous centers. PMID- 7989659 TI - [Keratitis in Lyme disease]. AB - The authors report the case of a 15-year-old female suffering from bilateral keratitis revealing Lyme's disease, 6 years after a tick bite. The corneas disclosed multiple hazy infiltrates adjacent to the limbus and in the midperiphery, from the superficial layers to pre-Descemet's membrane. The other systems involved were the joints, the skin (an atypical erythema chronicum migrans), and perhaps the peripheral nerves. The diagnosis was confirmed by indirect immunofluorescence assays in the serum of the patient who completely and rapidly healed with amoxicillin and systemic and topical steroids. The clinical and serological pitfalls which explain the frequent delayed diagnosis of Lyme's disease, its complications, especially ocular, and the therapeutic strategies are discussed. PMID- 7989658 TI - [Bilateral complete cryptophthalmos. Illustration with a case. Review of the literature]. AB - One case of bilateral complete cryptophthalmos is reported by the authors. Cryptophthalmos refers to a group of uncommon congenital eyelid malformation that can occur alone or in combination with multiple congenital anomalies. The mode of inheritance in the complete cryptophthalmos is discussed. The surgical exploration was described and the general features of the cryptophthalmos syndrome and its variants were reviewed. The authors submitted a list of the congenital anomalies associated. The family examination and the lack of family history pleaded in favour of a sporadic case. PMID- 7989660 TI - [Management of corneal microperforations during radial keratotomy]. AB - Corneal microperforations induce a corneal astigmatism since refractive effect is increased on the perforated meridian. To counteract this induced refractive error, we performed "flag" or tangenital incisions on the perpendicular meridian. PMID- 7989662 TI - [Clinical risk factors of vitreoretinal proliferations in rhegmatogenous retinal detachment]. AB - PVR is a complication of rhegmatogenous retinal detachment which can occur only in predisposed eyes. Preoperative PVR and postoperative PVR can develop solely in retinal detachments associated with retinal breaks related to vitreous traction (horse-shoe tears, operculated tears, crescent tears and paravascular tears of the postequatorial region). PVR never develops in retinal detachments due to retinogenic retinal breaks (atrophic holes in lattice, and oral dialysis). There are 3 independent risk factors for postoperative PVR whose role has been demonstrated: preoperative PVR, horse-shoe tears extending on 90 degrees or more of the eye circumference, and horse-shoe tears with a curled and fixed posterior edge. The role of preoperative choroidal detachment as an independent risk factor, although likely, remains to be demonstrated. Cryotreatment is a risk factor for postoperative PVR solely in predisposed eyes. An alternative method to cryo should be used in high risk eyes. PMID- 7989661 TI - [Iris tuberculosis. A propos of a case diagnosed by iridectomy]. AB - Ocular tuberculosis is currently rare in developed countries. We report a case of tuberculous nodular anterior uveitis which revealed primary tuberculosis in a 2 year old girl. This diagnosis was established on microscopic examination of a surgical iridectomy specimen. Thus, a metastatic retinoblastoma was eliminated. The subsequent clinical investigations showed that the girl's father had active pulmonary tuberculosis. PMID- 7989663 TI - [Treated bilateral diabetic retinopathy: risks in case of pregnancy]. PMID- 7989664 TI - Social support from friends and psychological distress among elderly persons: moderator effects of age. AB - In this study, the relationships among age, sex, friend support, and psychological distress are examined among elderly persons. Structural equation modeling and a longitudinal design are used to examine direct, indirect, and moderator (interaction) effects over a 22-month interval. Findings suggest that different causal processes operate among persons over the age of 70 (old-old) and those 50 to 70 years (young-old); the cross-lagged effects of friend support on distress and of distress on friend support are only observed in the older group. Compared to the young-old, the old-old receive less friend support at time 2 (T2) if they experienced psychological distress at time 1 (T1), and the old-old are more distressed at T2 if they received low levels of support at T1. As a result of this age interaction, the total effects of sex on distress and support at T2 are twice as large in the sample of old-old persons as in the sample of young-old persons. Such findings suggest that the old-old in general and old-old men in particular are especially vulnerable to psychological distress when losing friend support, and to lose friend support when experiencing psychological distress. Implications of these and other findings are discussed. PMID- 7989665 TI - Are black older adults health-pessimistic? AB - African Americans generally have more health problems than Whites, as manifested on most indicators of morbidity and mortality. The question pursued in this research is whether the more extensive health problems of minority older adults lead to a more pessimistic outlook on health. Previous research suggests that Black older adults who may be more pessimistic in their health orientations are thereby deterred from expecting health improvements from medical interventions. Using data from the Supplement on Aging to the Health Interview Survey conducted in 1984, a structural model is developed to examine the influence of functional morbidity and race on health promotion efforts and health assessments. Analysis of data from 3,237 respondents indicates that Black older adults report significantly more functional morbidity and more negative health assessments that White older adults. No direct racial differences were observed on health promotion efforts, but total effects show that Black persons are less likely to report promoting their health. When considering the four categories defined by race and sex, older Black women report the highest levels of functional morbidity and the most negative assessments of health. PMID- 7989666 TI - Job loss and alcohol abuse: a test using data from the Epidemiologic Catchment Area project. AB - The hypothesis that job loss affects the incidence of clinically significant alcohol abuse is tested using panel data from the Epidemiologic Catchment Area project. Results suggest that the incidence of clinically significant alcohol abuse is greater among those who have been laid off than among those who have not. However, employed persons in communities in which total employment is unexpectedly low are at reduced risk of becoming alcohol abusers. The implications of the results for economic policy and for mental health services are discussed briefly. PMID- 7989667 TI - Peer group structure and adolescent cigarette smoking: a social network analysis. AB - Social network theory and analysis are applied to examine whether adolescents who fill various social positions that characterize peer group structure differ in prevalence of current smoking. One thousand and ninety-two (1,092) ninth graders in one school system named their three best friends, allowing the identification of each adolescent as clique member, clique liaison, or isolate. At four of five schools, the odds of being a current smoker were significantly higher for isolates than for clique members and liaisons. The relationship was not explained by demographic variables or by the number of friends who smoke. PMID- 7989668 TI - Marital disruption and depression in a community sample. AB - The extent to which marital disruption causes poor mental health is not well characterized even after 20 years of research. This is due in large part to the fact that previous research has ignored the possibility of selection. The present analysis is based on a representative community sample and was designed to take a step toward correcting these problems and to explore a number of specifications overlooked in previous research. The aggregate results show that marital disruption is associated with an increase of approximately one-third of a standard deviation on a screening scale of depression over a three-year interval between waves of data collection. The effect is more pronounced among women than men and is confined to people other than those who are escaping marriages with serious long-term problems. No evidence is found that the depressogenic effect of marital disruption can be explained by increased financial pressures or other secondary changes in roles. However, increased emotional reactivity to these changes is shown to play a powerful role in promoting depression among the recently divorced. The implications and limitations of these results are discussed. PMID- 7989669 TI - Gender and health: some Asian evidence. AB - In Thailand, like the U.S., women's higher rates of illness and health service use imply that they are "sicker." But, as in the U.S., females live longer than males. Based on a large representative sample of Bangkokians, we find that married women report more sickness, are more likely to utilize health services and, according to self-reports, have poorer health. Western literature suggests five prominent explanations for gender differences in health: biological risks, acquired risks, psychosocial aspects of symptoms and care, health-reporting behavior, and prior health care and caretakers. However, analyses show that these explanations largely fail to account for morbidity differences between Thai men and women. The observed gender differences in health among Thais remain significant after eliminating pregnant women and new mothers, and after controlling for several aspects of acquired risk. Problems associated with the reproductive system among Thai women, along with greater psychological distress, appear to account for most of the gender differences in health. The theoretical implications of these findings are discussed. As for the apparent contradiction between gender differences in health and mortality in Thailand, the evidence indicates that Thai men, like their American counterparts, suffer from more serious chronic ailments that may explain their higher mortality rates. PMID- 7989670 TI - Physician's attitudes toward AIDS at different career stages: a comparison of internists and surgeons. AB - Physicians' responses to AIDS at different career stages and in different specialties were studied by surveying house staff (N = 438), faculty (N = 363), and applicants (N = 487) at six residency programs in internal medicine and six in surgery. House staff had more negative outlooks than senior medical students and faculty, reporting greater fear of exposure to AIDS and greater unwillingness to treat AIDS patients. Surgeons were more negative than internists on these dimensions. For all groups, concern about possible negative educational consequences of treating AIDS patients was largely a function of their amount of contact with AIDS patients. Comparing willingness to treat AIDS and nine other conditions, AIDS consistently ranked low, along with Alzheimer's disease, alcoholism, and drug dependency. The findings have practical implications for hospitals and training programs. In addition, they raise issues concerning the impact of training on professional socialization, and call into question physicians' commitment to the professional norm of treating all patients regardless of provider self-interest, patient social characteristics, or medical uncertainty. PMID- 7989671 TI - D.D.T. resistance in Sergentomyia shorttii (Diptera: Psychodidae) in Kamrup, Assam--first report in Sergentomyia genus. AB - S. shorttii, a common phlebotomine sandfly species of Assam, was tested for susceptibility to commonly used insecticides, D.D.T., malathion and Fenitrothion in Kamrup district, Assam. Tests carried out by WHO test kits showed 100 per cent mortalities against discriminating concentrations of malathion (5 per cent) and Fenitrothion (1 per cent). With D.D.T., in 1 hr. exposure mortalities recorded were 54.5 and 64.4 per cent, whereas in 24 hr. exposure mortalities were 75 per cent and 90 per cent. The area has been under continuous D.D.T. spraying since the beginning of NMEP in 1958, and high selection pressure appears to have precipitated D.D.T. resistance in this partly exophilic species. PMID- 7989672 TI - Prevalence of intestinal parasites in rural areas of district Shahjahanpur, Uttar Pradesh. AB - A stool survey was carried out in some of the villages of Dadraul and Bhawal Khera PHC's of district Shahjahanpur (Uttar Pradesh). Out of 381 individuals examined 111 (29.2 per cent) were found positive for one or the other intestinal parasite. Ascaris lumbricoides superseded all the parasites by showing a positivity of 17.85 percent. Other parasites found were Hookworm, Hymenolepis nana, Tapeworm, Trichuris trichiura, Enterobius vermicularis, Entamoeba histolytica, E. coli and Giardia lamblia. Parasitic load was slightly higher in females (33.59 per cent) than males (28.18 per cent). The highest positivity was encountered in the age groups between 6 to 14 years. This high prevalence of intestinal parasites may be due to the lack of awareness about personal cleanliness and hygiene and illiteracy among rural women. Majority of them had helminthic infections. It is concluded that in rural areas of district Shahjahanpur intestinal helminthic infections are more prevalent that protozoan infections. PMID- 7989673 TI - Plasmodium falciparum sensitivity in "in-vivo" and its distribution in geo ecological zones of Gujarat. AB - Plasmodium falciparum sensitivity test in "in-vivo" carried out in 450 patients revealed, parasite clearance in 66.45 percent cases with 25 mgm/kg body wt of chloroquine. Mean parasite clearance time (MPCT) of sensitive and R I, resistant cases reached near parallelism with an early recrudescence in RI cases indicating stabilisation of genetic change in the parasite strain. The analysis of data revealed that proportionately higher resistance was recorded in coastal area having deciduous (wet) forest ecotype followed by plains of deciduous dry forest and semi arid/arid ecotypes. PMID- 7989674 TI - Larvivorous capacity of some indigenous fish of Haryana state. AB - Studies were undertaken to assess the role of some indigenous fish of Haryana state for the biological control of mosquitoes. Total of 28 fish species were encountered. Only six fresh water fish species Puntius ticto, Colisa fasciata, Aplocheilus panchax, Rasbora daniconius, Chanda nama, and Esomus danricus species possessed good feeding potential on mosquito larvae. The small size, well developed eyes and position of the mouth seem to be probably the important factors helping their voracity on mosquito larvae. These fish are either surface, subsurface or column feeders. PMID- 7989675 TI - An estimate of kala azar in 1991 in district Vaishali and Bihar. PMID- 7989676 TI - Preparedness for disaster mitigation--Shimla response. PMID- 7989677 TI - Comparative efficacy of chloroquine and amodiaquine in Plasmodium falciparum strain of north-eastern India. AB - The present study describes the comparative efficacy of chloroquine and amodiaquine in two different presumptive therapy areas of north eastern India. The study recorded insignificant differences in respect of Mean Parasite Clearance Time (MPCT) of sensitive cases, MPCT and Mean Parasite Recrudescence Time (MPRT) of RI resistant cases and recrudescence rate in chloroquine and amodiaquine therapy areas. It is concluded that amodiaquine is not a superior drug as compared to chloroquine. In the chloroquine resistance area, Plasmodium falciparum developed cross resistance to amodiaquine and this phenomenon appears to be unidirectional. However, amodiaquine may help to slow-down the rate of precipitation of higher grade of resistance. PMID- 7989678 TI - Absence of Phlebotomus argentipes Ann & Brun. (Diptera: Psychodidae) the vector of Indian kala-azar from Kamrup district, Assam. AB - In the past Assam was devastated by epidemics of Kala-azar. However, inspite of resurgence of this disease in Bihar and neighbouring areas Assam has remained untouched by this disease since the mid 1950s so far. The study undertaken in Kamrup district, sought to provide an entomological explanation for Assam's present freedom from Kala-azar. Sandfly collections were made in 15 villages. Three different methods were used; namely hand collections by aspirator and torch, sticky traps and examination of soft parts of cattle in the villages for mating swarms. 1049 sandflies were collected which did not include any specimens of P. argentipes. The vector of Indian Kala-azar has either been eliminated by continuous insecticide spraying in this high P. falciparum, and chloroquine resistance area or reduced to such low levels of prevalence that routine sampling methods are unable to reveal its presence. The implications of this finding are discussed in relation to Kala-azar control in India, in general. PMID- 7989679 TI - Cryptosporidiosis in patients with diarrhoea in five hospitals in Nigeria. AB - A total of 413 soft, loose or watery stool specimens from patients with acute diarrhoea were screened for presence of Cryptosporidium oocysts. Safranin methylene blue staining technique was used for detecting Cryptosporidium oocysts in the stool samples. The oocysts were identified in 52 (12.5 per cent) of the samples, while 69 samples (16.7 per cent) showed mixed infections. Children between the ages of 2 and 15 years were most infected by this parasite while infection occurred more in females than males for all age groups. These findings indicate that Cryptosporidium is an important etiologic agent of diarrhoea. Hence there is need to include its identification in laboratory analysis of diarrhoeal stool samples. PMID- 7989680 TI - Laboratory and field evaluation of Bacillus thuringiensis and B. sphaericus against mosquito larvae. AB - Laboratory and field trials were carried out with two formulations of Bacillus thuringiensis and four strains of Bacillus sphaericus (B 42, B 64, B 87 and B 33) against mosquito larvae in different breeding habitats of Tezpur, Assam. LC90 of B. thuringiensis var israelensis (formulation Teknar) against Ae. albopictus, Cx. quinquefasciatus and Cx. gelidus were recorded as 0.443, 0.453 and 2.15 ppm respectively and LC90 of B. thuringiensis (Deltox: VCRC B-17) against Ae. albopictus, Cx. quinquefasciatus, Cx. gelidus and Cx. malayi were 8.414, 11.22, 5.24 and 6.761 ppm respectively. LC90 of B. sphaericus strains B 42, B 64, B 87 and B 33 against Cx. quinquefasciatus were 0.055, 0.115, 0.046 and 0.257 ppm respectively. At the dosage of 1 l/ha 87 per cent mortality was achieved after 24 hrs with Bti and it increased to 90-95 per cent at 1.5 l/ha. In polluted cemented drains 93-97 per cent kill of Cx. quinquefasciatus was observed at 2.5 l/ha. Out of four strains of B. sphaericus evaluated, strain B 87 was found to be the most effective as 87-96 per cent kill was achieved with only 0.1 kg/ha for Cx. quinquefasciatus, Cx. vishnui and A. vagus. For others 0.2 kg/ha dosage, eliminated 96-100 per cent Cx. vishnui gr. for B 42, 92-93 per cent for B 64 and 90-93 per cent for B 33 strain. PMID- 7989681 TI - An outbreak of viral hepatitis in a housing complex of north Calcutta. AB - In a housing complex of North Calcutta, a sudden outbreak of hepatitis occurred between September 1988 and January 1989. Of 620 residents, 8.5 per cent were affected. Majority of the cases occurred among the adult population and the case fatality rate was 3.8 per cent. The epidemic was common source with peak incidence in the month of November. The source of infection was most likely drinking water supplied by the Municipal Corporation which was found to be contaminated by faecal coli. Epidemic was suspected to be caused by enterically transmitted Non A Non B hepatitis virus as the serological testing of all 18 blood samples were negative for anti-HAVIgM titre and only one sample was positive for HBsAg. PMID- 7989682 TI - An epidemiological profile of gastro-enteritis deaths in Delhi state. AB - This paper describes epidemiological features of 75 gastro-enteritis deaths that occured in 22 major hospitals of Delhi during 1990-92. Three fourth's of deaths were in under five years of age group and more than half were infants. In 84 per cent, diarrhoea was of an acute watery type. Dehydration was the commonest immediate cause of death, while malnutrition was the commonest associated cause. No ORS/SSS/HAF was given to one fourth of the patients. Close relatives of two third's of deceased were either not aware at all about ORS/SSS or had incorrect information. In 87 per cent, food intake was either stopped or had been restricted. The study emphasizes the need for an intensive IEC campaign for prevention, and for better case management in the hospitals coupled with appropriate reorientation training of private practitioners. PMID- 7989683 TI - Minimizing the pain of local infiltration anesthesia for wounds by injection into the wound edges. AB - This study on low contamination wounds was conducted to compare the pain of local infiltration anaesthesia administered into the skin surrounding the wound with administration directly into the incised edges of the wound. Eighty-one adult patients were randomized by date of presentation to receive infiltration anesthesia by one of the two methods. Pain of anesthetic administration was rated on a visual analogue scale and recorded as a pain score in millimeters. The results demonstrated that the average pain score for infiltration into the wound was significantly lower than the average pain score for infiltration into skin surrounding the wound. PMID- 7989685 TI - Pneumoscrotum after blunt chest trauma. AB - A case of pneumoscrotum after a suicide jump with blunt chest trauma and chest tube placement is reported. Pneumoscrotum itself has little clinical importance, but it is essential for the clinician to determine the origin of the air, and a careful search for the source of air is necessary. Three possible routes of air in the pneumoscrotum are reviewed. Many reported cases, including this case, had a cause distant from the pelvis: air dissected subcutaneously to the scrotum because of pneumothorax, tube thoracostomy, and air leak combined with ventilatory resuscitation efforts. PMID- 7989684 TI - The efficacy of routine head computed tomography (CT scan) prior to lumbar puncture in the emergency department. AB - The efficacy of using unenhanced head computed tomography (CT scans) as a routine screening procedure prior to lumbar puncture in the emergency department is studied retrospectively by comparing opening pressure during lumbar puncture to CT scan diagnosis in 42 patients. No correlation was found between CT scan findings and opening pressure. PMID- 7989686 TI - Widened mediastinum in acute trauma: a complication of central venous catheterization. AB - We report a case of mediastinal widening simulating aortic rupture and resulting from fluid infused into the mediastinum via a percutaneously placed subclavian pulmonary artery introducer sheath in an acutely injured patient. The use of such catheters for resuscitation of acutely injured patients is presented, along with reported complications and their diagnosis. Necessary precautions during the use of these catheters are discussed. PMID- 7989687 TI - Necrotizing fasciitis of the upper extremity. AB - The standard treatment of necrotizing fasciitis is early recognition and early surgical debridement of all necrotic tissues. The use of antibiotics alone does not prove to be effective unless coupled with aggressive surgical treatment. We present a case of necrotizing fasciitis of unknown cause in a child. Although the only treatment was IV antibiotics and fasciotomy without any debridement, the patient survived the disease with minimal morbidity. PMID- 7989688 TI - Vogt-Koyanagi-Harada syndrome: case report and review. AB - The case of an adolescent male with a painful red eye is presented, and the emergency department differential diagnosis is reviewed. The patient had Vogt Koyanagi-Harada (VKH) syndrome, a panuveitis with extraocular systemic manifestations. The syndrome may result in permanent visual loss but is quite sensitive to corticosteroid therapy. Early ophthalmologic consultation from the emergency department is essential for prompt institution of definitive therapy and preservation of vision. The salient features and diagnostic evaluation of VKH are reviewed. PMID- 7989690 TI - Hemodynamics of cough cardiopulmonary resuscitation in a patient with sustained torsades de pointes/ventricular flutter. AB - A 43-year-old female with old myocardial infarction and stenosed bypass grafts developed sustained Torsades de Pointes/ventricular flutter (rate = 300-400 beats per minute) during coronary arteriography after contrast injection to the diagonal graft. Cough-CPR (rate = 37/min) was started within 5 s of dysrhythmia initiation and continued through two defibrillation attempts (200 and 360 joules), and IV lidocaine was administered until return of spontaneous circulation 62 s later. The patient never lost consciousness during this very rapid dysrhythmia. Certain cardiac arrest resuscitation measures (namely, initial defibrillation attemps, IV lidocaine administration) can thus be initiated in a patient while performing cough-CPR and maintaining adequate cerebral perfusion. During the dysrhythmia with Cough-CPR: (a) aortic systolic pressures averaged 100 mmHg--this has commonly been observed in other reports, and (b) aortic diastolic pressures were always > or = 50 mmHg and averaged 63 mmHg, which has seldom been this high during cough-CPR. Dysrhythmia reversion occurred 4 s after the second defibrillation attempt and 80 msec after the peak of the highest cough-generated aortic pressure pulse (128 mmHg). Cough-induced ventricular tachycardia reversion has previously been reported; this may have acted in concert with electrical defibrillation to facilitate dysrhythmia reversion. The patient recovered without incident. PMID- 7989689 TI - Delayed hypotension after overdose of sustained release verapamil. AB - We present the case of a 25-year-old woman who, although normotensive on presentation, had a severe hypotensive episode more than 12 h after initial ingestion of sustained release verapamil. Management of asymptomatic patients who have overdosed on a sustained release preparation of a calcium channel blocker is discussed. PMID- 7989691 TI - Practical uses of end-tidal carbon dioxide monitoring in the emergency department. AB - Qualitative and quantitative measurement of the carbon dioxide (CO2) concentration in respiratory gases is readily available with current technology. End-tidal CO2 (PetCO2) monitoring, whether by qualitative colorimetric methods or by solid-state spectrophotometric techniques, is becoming increasingly valuable in the Emergency Department (ED). These techniques offer a practical adjunct to the ED management of critical interventions including endotracheal intubation, conscious sedation, and cardiopulmonary resuscitation. PMID- 7989692 TI - Tissue adhesive wound repair revisited. AB - The purpose of this experimental study was to compare the effect of a tissue adhesive, N-butyl-2-cyanoacrylate, on the wound's ability to resist infection and gain strength to the effect of percutaneous polypropylene suture. Percutaneous sutures damaged host defenses, inviting the growth of bacteria to a level that was significantly greater than that encountered with the tissue adhesive. Immediately after wound closure, percutaneous sutures provided a more secure closure, as measured by breaking strength, than did tissue adhesives. Seven days later, the breaking strengths of wounds closed by tissue adhesives did not differ significantly from those repaired with percutaneous sutures. Tissue adhesive closure requires less psychomotor skills than suture closure and is accomplished more rapidly than suture closure. PMID- 7989693 TI - Compartment syndrome: a complication of acute extremity trauma. AB - Compartment syndrome is a serious potential complication of trauma to the extremities. Fractures, crush injuries, burns, and arterial injuries, among others, can result in increased tissue pressure within closed osseofascial or compartmental spaces. Prolonged exposure to elevated pressure can result in nerve and muscle necrosis. Extreme pain unrelieved with analgesia, subjective complaint of pressure, pain with passive muscle stretching, paresis, paresthesia, and intact pulses, in the presence of a physically tight compartment, should alert the physician to the presence of a compartment syndrome. The diagnosis is a clinical one, but it may be aided by measurements of intracompartmental tissue pressures. Compartment syndrome is a surgical emergency requiring prompt treatment by fasciotomy. Time is a critical factor; the longer the duration of elevated tissue pressure, the greater the potential for disastrous sequelae. Emergency medicine providers must be cognizant of this clinical syndrome so that early emergent surgical consultation can be obtained to avoid complications. PMID- 7989694 TI - Emergency department treatment of migraine, tension, and mixed-type headache. AB - The complaint of headache is frequently encountered in the emergency department, but most patients with cephalalgia have a benign etiology for their pain. At least 90% of patients presenting with headache are diagnosed as suffering from benign vascular or muscle-tension (for example, migraine, tension, or mixed-type) headache. There is no consensus on the ideal therapeutic approach to these patients. Classically utilized narcotic therapy suffers from problems with efficacy, relapse, and potential for abuse and addiction. However, other agents have successively proved to be imperfect as well, despite the many therapeutic approaches that have been suggested in the medical literature. While no one drug has emerged as clearly superior for treatment of acute benign headache, recent investigations have clarified the role of certain therapies. This review is intended to familiarize emergency physicians with the latest information on most recommended therapeutic approaches to the patient with headache. PMID- 7989695 TI - Streptococcal pharyngitis: a review of pathophysiology, diagnosis, and management. AB - Pharyngitis is an illness frequently treated by emergency physicians and primary care practitioners. It is the subject of much controversy regarding optimal treatment in the acute care setting. This review discusses pertinent aspects of the pathophysiology, clinical features, diagnosis, and treatment based on available literature. This review is also meant to serve as a bibliographic resource for some of the controversies of this complex topic. PMID- 7989696 TI - Joseph Larner's personal odyssey: search for the cause and cure of non-insulin dependent diabetes mellitus. AB - Over the last five decades, Joseph Larner has tirelessly pursued scientific studies of the mechanism of insulin action, which are now providing new insight into the cause, diagnosis, and cure of non-insulin-dependent diabetes mellitus (NIDDM). Larner demonstrated that D-chiro-inositol (D-CI) is virtually absent in the urine of patients with NIDDM. Consequently, he suggested that the insulin resistance seen in such patients is related to the absence of one of the mediators of insulin action containing D-CI. Moreover, Larner demonstrated that this D-CI deficiency and insulin resistance could be corrected by the administration of D-CI to experimental diabetic and insulin-resistant animals. From this pioneering research, the potential for therapy using D-CI in NIDDM is evident and must be evaluated expeditiously. PMID- 7989697 TI - Revisiting fluoxetine (Proxac) and suicidal preoccupations. AB - Several reports were published in the psychiatric literature in 1990 and 1991 documenting fluoxetine (Prozac) causing patients to consider or attempt suicide. During the following 2 years, retrospective studies appeared in the medical literature that seemed to indicate that suicidal preoccupation was not related to the antidepressant fluoxetine (Prozac) but was probably a symptom of the depressive illness. Recent studies have suggested, however, that fluoxetine (Prozac) may in fact lead to suicidal behavior because the drug appears to adversely affect serotonergic neuronal discharge and induce an akathisia-like extrapyramidal reaction. While fluoxetine (Prozac) has a very favorable side effect profile compared to the tricyclic antidepressants, it may cause akathisia and induce a small subset of patients to consider or attempt suicide. PMID- 7989699 TI - The world of emergency medicine. PMID- 7989698 TI - Emergency department follow-up of emergency conditions: why not? PMID- 7989700 TI - Objectives to direct the training of emergency medicine residents on off-service rotation in cardiology, Part 2. AB - This article is the second of two parts outlining the objectives for a resident rotation in cardiology. Cardiology is offered as an off service rotation or an elective at some emergency medicine residency training programs. An organized core curriculum may provide a structured learning environment to help ensure that certain principles and objectives important to the practice of emergency medicine are learned. We have developed a written core curriculum containing a subject content list, learning objectives, and references for emergency medicine residents on cardiology services. This is a continuation of a series of objectives for off-service rotations for emergency medicine residents. PMID- 7989701 TI - There are still cathedrals in Toronto. PMID- 7989702 TI - The utility of a bone scan in the diagnosis of clinical scaphoid fracture. AB - The incidence of true scaphoid fracture and the value of radionuclide scan was evaluated in a 1-year retrospective review of 54 emergency department patients with a preliminary diagnosis of clinical scaphoid fracture (snuff box tenderness and negative initial X-ray study). All emergency department charts of patients with a discharge diagnosis of clinical scaphoid fracture were reviewed to determine the number ultimately found to have a true scaphoid fracture and to ascertain how the diagnosis was actually achieved. All patients were managed by immobilization in a thumb spica cast for a period of 10-14 d, with repeat clinical assessment and radiographs at that time. The diagnosis of true scaphoid fracture was confirmed radiographically at the time of reassessment or, in the case of persistent tenderness and negative repeat radiographs, by the use of a technetium bone scan. In our study group, only 8 of 54 patients (14.8%) were found to have a final diagnosis of true scaphoid fracture. In 75% (6/8) of these patients, the diagnosis was made by technetium bone scans, as the radiographs remained negative at the time of reassessment. In addition, a bone scan revealed the presence of two previously unsuspected fractures (one distal radius fracture and one triquetral fracture) in two patients with continued clinical tenderness. This study confirms the previously reported low incidence of scaphoid fractures in patients with a diagnosis of clinical scaphoid fracture. It also demonstrates the importance of technetium bone scan as a diagnostic tool of increased sensitivity, as compared to traditional radiographs, in detecting the presence of scaphoid fractures and in detecting other clinically unsuspected fractures in this group of patients. PMID- 7989703 TI - Nucleoside analogs in the treatment of chronic viral hepatitis. Efficiency and complications. PMID- 7989704 TI - Therapy of chronic hepatitis B with a 6-month course of ribavirin. AB - Ribavirin is a nucleoside analogue with broad spectrum antiviral activity that has been shown to inhibit viral replication in the woodchuck model of hepatitis B virus infection. We studied the effect of ribavirin on viral replication in 18 patients with chronic hepatitis B who were positive for hepatitis B e antigen. Patients were randomized to receive a 24-week course of oral ribavirin at a dose of either 800, 1000, or 1200 mg/kg per day. All patients completed 24 weeks of treatment and an additional 24 weeks of follow up without significant side effects except for mild, reversible hemolytic anemia. Response to ribavirin was similar among all three dosage groups (p > 0.5); hence the data were pooled and analyzed together. Mean hepatitis B virus DNA levels decreased from 162.7 (95% confidence interval, 106 to 219) pg/ml before treatment to its lowest level of 114.3 (95% confidence interval, 53 to 175) pg/ml at week 20 (p < 0.05). Two patients became negative for HBV DNA and lost hepatitis B e antigen. Mean serum alanine aminotransferase activity decreased markedly from 131.1 (95% confidence interval, 84 to 178) U/l before treatment to 62.4 (95% confidence interval, 48 to 77) U/l at the end of 24 weeks of ribavirin (p < 0.05) and became normal in four patients (22%). Aminotransferase levels returned to baseline within 4 weeks once ribavirin was discontinued, while HBV DNA concentrations remained below baseline even at the end of 24 weeks of follow up.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7989705 TI - Lymphocyte reactivity to ex-vivo drug antigens in drug-induced hepatitis. AB - The diagnosis of drug-induced hepatitis is usually based on clinical criteria, with emphasis on both the temporal relationship between drug intake and liver injury and the exclusion of alternative causes. In vitro tests of lymphocyte sensitization to drugs are considered to have a low sensitivity. We investigated the possibility of detecting lymphocyte reactivity to drugs in drug-induced hepatitis by analyzing the lymphocyte proliferative responses to ex-vivo drug or metabolite antigens to improve the sensitivity of the in vitro test. Lymphocyte proliferative responses to five different concentrations of the drug and to ex vivo drug antigens (serum collected from normal subjects after the ingestion of the drugs) were analyzed in 25 patients with a clinical diagnosis of drug-induced hepatitis, 27 healthy subjects and 10 individuals with a recent exposure to the same drugs without development of adverse drug reactions. In seven of the 25 patients, lymphocyte reactivity to drugs was detected (28%). The use of sera collected from healthy volunteers after drug intake (ex-vivo drug antigens) and the addition of a prostaglandin inhibitor to the cultures allowed the detection of lymphocyte sensitization in seven additional cases, increasing the detection ability from 28% to 56%. We suggest that the use of ex-vivo drug antigens may represent a significant contribution to the identification of the drug involved in cases of drug-induced hepatitis. PMID- 7989707 TI - Positive and negative hepatitis C virus RNA strands in serum, liver and peripheral blood mononuclear cells in anti-HCV patients: relation with the liver lesion. AB - To investigate the replicative hepatitis C virus status and its relation to liver damage, serum, peripheral blood mononuclear cells and liver-paired samples from 45 untreated hepatitis C virus infected patients (38 with chronic hepatitis, three with minimal changes, and four with normal liver) were studied by nested polymerase chain reaction, using primers from the 5' untranslated region. Positive HCV-RNA strand was detected in serum (69%), peripheral blood mononuclear cells (100%) and liver samples (100%). The presence of negative HCV-RNA strand was confirmed using specificity controls assays and was only detected in liver and peripheral blood mononuclear cells samples, (95% and 82%, respectively). No correlation between the presence of negative HCV-RNA strand in peripheral blood mononuclear cells and positive HCV-RNA strand in serum was found, whereas serum HCV-RNA was not detected in patients without negative HCV-RNA strand in the liver. Both positive and negative HCV-RNA strands were found in liver and peripheral blood mononuclear cells of four patients with normal liver histology, and three with minimal changes. Furthermore, the presence of HCV-RNA in serum did not correlate with the alanine aminotransferase values and the histological activity index. These data confirm the existence of replicative intermediates in the liver, not only from patients with histologically proven chronic hepatitis, but also from those with normal liver, suggesting the existence of hepatitis C virus in true healthy carriers. PMID- 7989706 TI - Morphometry of sinusoids and portal hypertension in non-alcoholic cirrhosis. AB - To examine whether structural changes in hepatocytes and/or sinusoidal areas contribute to the portal hypertensive state in non-alcoholic cirrhosis, a new method of morphometric analysis using a computer-aided color image analyzer was performed in 16 patients with non-alcoholic cirrhosis, which allowed quantitative evaluation of various morphometric parameters of sinusoids and hepatocytes. The sinusoidal pressure gradient was estimated theoretically with these and clearance parameters using Poiseulle's equation and compared with the hepatic venous pressure gradient measure by hepatic vein cannulation. A significant relationship was found between the hepatic venous pressure gradient and sinusoidal volumetric ratio (r = -0.598, p < 0.05), but not between mean hepatocyte volume and sinusoidal volumetric ratio (r = 0.416, NS), or the hepatic venous pressure gradient (r = 0.371, NS). The estimated sinusoidal pressure gradient showed a significant relationship with the hepatic venous pressure gradient (r = 0.637, p < 0.01). However, the absolute values of the former were much lower than those of the latter. Therefore, in non-alcoholic cirrhosis, although sinusoidal stenosis not caused by hepatocyte swelling may lead to increased vascular resistance, other factors must also play a significant role. PMID- 7989708 TI - Autoimmune chronic active hepatitis responsive to immunosuppressive therapy evolving into a typical primary biliary cirrhosis syndrome: a case report. AB - The evolution from a characteristic picture of autoimmune chronic hepatitis type I to primary biliary cirrhosis is reported in a middle-aged woman. The initial diagnosis of autoimmune chronic liver disease was based on clinical, bio serological and histological grounds. It was further confirmed by complete remission following immunosuppressive treatment and prompt relapses at the time of therapy withdrawal. After 7 years, the characteristics of liver disease were altered with increased biochemical cholestasis and serum IgM concentrations, positivation of previously negative anti-M2 antimitochondrial antibodies and the appearance of a typical histological picture of stage I primary biliary cirrhosis. We believe that this is the first reported case in which autoimmune chronic hepatitis highly responsive to immunosuppressive therapy has been followed by the development of a characteristic picture of primary biliary cirrhosis. PMID- 7989709 TI - Interferon therapy in liver/kidney microsomal antibody type 1-positive patients with chronic hepatitis C. AB - The association between liver/kidney microsomal antibody type 1 and adult cases of hepatitis C virus-related chronic liver disease has been firmly established. In the presence of both markers, evidence of autoimmunity (liver/kidney microsomal antibody type 1) and actual viremia (serum HCV RNA), the therapeutic dilemma arises between steroids, which are beneficial to autoimmune but deleterious to viral diseases, and interferon-alpha, which may exacerbate an autoimmune disorder. Six patients with liver/kidney microsomal antibody type 1 and serum HCV RNA were given interferon-alpha: three showed a response pattern similar to that observed in autoantibody-negative chronic hepatitis C cases; the other three developed a sharp transaminase peak, which was not followed by HCV RNA clearance. Considering the brisk flare-up of liver cell necrosis, interferon alpha treatment proved to be dangerous in the above three liver/kidney microsomal antibody type 1/HCV RNA positive cases. Subsequent steroid administration reduced alanine aminotransferase peaks, but may be harmful in viral infections. Therapeutic alternatives are needed: they will probably include pure antivirals (exerting no immunostimulatory effects) with or without immunosuppressive drugs. PMID- 7989711 TI - Atrial natriuretic factor in cirrhosis: relationship to renal function and hemodynamic changes. AB - Plasma atrial natriuretic factor concentrations and different hemodynamic parameters, including the evaluation of femoral arteriovenous shunting by measuring the arteriovenous difference of oxygen content (Ca-vO2), were determined in eight healthy subjects and 24 patients with cirrhosis without renal failure (group I: seven patients without ascites, group II: nine patients with ascites and UNaV > 10 mEq/24 h and group III: eight patients with ascites and UNaV < or = 10 mEq/24 h). Atrial natriuretic factor was 34 +/- 4.7 pg/ml in the control group and 44.28 +/- 5.4, 67.89 +/- 8.8 and 84 +/- 10.8 pg/ml in groups I, II and III respectively (p < 0.001. group III vs. I and control and II vs. control). Atrial natriuretic factor directly correlated with cardiac index (p < 0.01), blood volume (p: 0.01), femoral blood flow (p < 0.01) and inversely with systemic and femoral vascular resistances (p < 0.02), Ca-vO2 (p < 0.01), serum albumin (r: -0.61; p < 0.01) and prothrombin index (r: -0.63; p < 0.02). These results indicate that plasma atrial natriuretic factor is increased in patients with cirrhosis, especially in those with advanced disease and marked renal sodium retention. This suggests that in cirrhosis, arteriolar vasodilation and peripheral arteriovenous shunting influence renal function while inducing a state of overflow at the central venous compartment leading to increased atrial natriuretic factor secretion. Increased production of this vasodilatory hormone may thus contribute to the hyperkinetic circulation of cirrhosis. PMID- 7989710 TI - Impact of immunoprophylaxis and patient selection on outcome of transplantation for HBsAg-positive liver recipients. AB - We have studied the roles of immunoprophylaxis, patient selection policy and coexistent hepatitis D virus infection in the outcome of 56 HBsAg-positive elective liver transplant recipients. Twenty-nine unselected patients not treated with immunoprophylaxis formed group 1 and were compared to a recent consecutive series of 27 patients (group 2) in whom pre-transplant serological status was determined and who received immunoprophylaxis. One-year actuarial HBsAg serological recurrence rates were 48% in group 2 and 90% in group 1 with particular improvement in recipients who were either HBV DNA-negative or who had co-existent hepatitis delta virus infection. One-year patient survival has improved from 62% in group 1 to 86% in group 2 with improvements in hepatitis delta virus-negative and replicating recipients. Patients who have either co existent hepatitis delta virus infection or are in group 2 have 1-year survival rates comparable to elective HBsAg-negative recipients (19/21 (90%), 22/27 (86%) vs 87%, respectively). In the event of recurrence, severe graft injury is diminished in recent patients and in those with coexistent delta infection who also have lower levels of circulating HBV DNA. Retransplantation for associated graft injury has a poor prognosis irrespective of administration of immunoprophylaxis. In elective liver recipients, immunoprophylaxis and/or hepatitis delta virus infection modulate hepatitis B virus recurrence and associated graft injury with consequent improvement in patient survival. PMID- 7989712 TI - Effect of verapamil on hepatic reperfusion injury after prolonged ischemia in pigs. AB - This study investigated the effect of verapamil on prolonged and severe ischemic injury and elucidated the association of the calcium blocking action with cellular injury, assessing changes in hepatic calcium concentrations during ischemia and reperfusion in pigs. Hepatic ischemia was produced for 180 min by clamping both the hepatic artery and portal vein during temporary portacaval shunt performed before the induction of ischemia. Pigs were divided into two groups: the animals in the verapamil group (Group V, n = 6) received continuous administration of 0.025 mg/kg per min of verapamil intraportally for 20 min before ischemia. The control group (Group C) received nothing. A better survival rate was observed in Group V than in Group C (p < 0.01), but serum aspartate aminotransferase was higher in Group V after reperfusion (p < 0.05). There were no significant changes in hepatic calcium concentrations during ischemia in either group, but it increased immediately after reperfusion in both groups. However, no significant difference was found between the two groups. Recovery of the pyruvate/lactate ratio in Group V tended to be better after reperfusion compared to Group C (p = 0.08). These data suggest that the pre-ischemic administration of verapamil produced better survival in animals after prolonged normothermic ischemia. However, the reperfused liver suffered more severe damage in the first 6 h after reperfusion in the verapamil-treated animals. Moreover, there seemed to be very little blocking action of calcium influx. A reduced oxygen requirement may be involved in the protective action of verapamil on animal survival. PMID- 7989713 TI - Complete congenital heart block in autoimmune hepatitis (SLA-positive). AB - Complete congenital heart block is a serious complication of neonatal lupus erythematosus which most often occurs in children of mothers suffering from connective tissue disease. We report the occurrence of complete congenital heart block associated with autoimmune hepatitis (SLA-positive). A 32-year-old woman was treated for more than 10 years for autoimmune hepatitis (SLA-/ANA-positive) and remained in clinical remission under immunosuppressive therapy. She showed an MHC-haplotype typical for autoimmune hepatitis (A1, B8, DR3). After a normal first pregnancy, an emergency caesarean section was performed in the 32nd week of her second pregnancy because of fetal bradycardia. The child died a few hours after delivery of complete congenital AV-block. Retrospective analysis of the maternal serum showed the emergence of SS-A/Ro-antibodies prior to the second pregnancy. The maternal serum antibodies were reactive with the 52 kD SS-A/Ro antigen, as demonstrated by immunoblot employing recombinant SSA/Ro-antigen. The occurrence of complete congenital heart block has been shown to be associated with the presence of SS-A/Ro antibodies as well as the MHC-haplotype DR3. With respect to this genetic linkage, pregnant patients with autoimmune hepatitis and the MHC-haplotype DR3 should be examined for the presence of SS-A/Ro-antibodies. They should be closely followed during pregnancy to enable early detection of the development of congenital heart block, as prevention by plasmapheresis plus dexamethasone may be possible at an early stage. PMID- 7989714 TI - Expression of hepatocyte growth factor mRNA, and c-met mRNA (hepatocyte growth factor receptor) in human liver tumours. AB - We have quantified mRNA for the hepatocyte growth factor and its putative receptor the c-met proto-oncogene protein product, in a series of human primary and secondary liver tumours and adjacent non-neoplastic liver. In all hepatocellular cancers, hepatocyte growth factor 6 kb mRNA expression was less (mean 23.93% +/- 6.33% S.E.M. n = 7) in the tumours than in the adjacent normal liver. Both relative over- and under-expression of c-met transcripts were found in tumour tissue compared to non-neoplastic liver. Thus hepatocellular cancer tissue does not over-express mRNA for hepatocyte growth factor, though this growth factor might play a role in hyperproliferative states leading to liver cancer. PMID- 7989715 TI - Serum bile acids and cholestasis in alcoholic hepatitis. Relationship with usual liver tests and histological features. AB - Cholestasis is a biochemical and/or histological feature observed in some patients with alcoholic liver disease and is mainly related to alcoholic hepatitis. Accumulation of bile acids in the liver could be pathogenic in alcoholic hepatitis. The aim of this study was to assay serum bile acids in patients with alcoholic hepatitis and to assess the relationship between these parameters, the usual liver tests and the histological features of alcoholic hepatitis. Thirty-six patients (median 51 years, 19 females and 17 males) with biopsy-proven alcoholic hepatitis were included in the study. Cirrhosis was present in 27 patients. Serum bile acids were assayed by high performance liquid chromatography. Three histological scores (alcoholic hepatitis, fibrosis, and cholestasis) were established on each liver sample by two independent pathologists. Serum bile acid concentrations were increased in 35 patients (97%). The median concentration of total serum bile acids was 41.6 mumol/l (range 3 293), with an increase in primary bile acids (95.7% of total bile acids), mainly chenodeoxycholic acid (median 27.5 mumol/l, range 3-184). In contrast, serum bilirubin levels were increased in only 26 patients (72%). Histological cholestasis was present in 14 patients (38%). There was no significant correlation between the alcoholic hepatitis and cholestasis scores (r = 0.01, p = 0.9). A significant correlation was noted between the alcoholic hepatitis score and serum total bile acid (r = 0.34, p = 0.04), cholic acid (r = 0.38, p = 0.03) and chenodeoxycholic acid (r = 0.32, p = 0.05) levels.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7989716 TI - Suicide associated with alfa-interferon therapy for chronic viral hepatitis. AB - We report on two attempted suicides and one successful suicide during or shortly after alfa-interferon therapy for chronic viral hepatitis. While on therapy, all three patients developed a psychiatric disorder leading to their suicidal behavior. In a survey of 15 European hospitals, three cases of attempted and two of successful suicide during alfa-interferon therapy for chronic viral hepatitis, were additionally reported. None of the patients had a psychiatric history. Alfa interferon is known to lead to neuropsychiatric symptoms, and our observations strongly suggest that these mental disorders could lead to suicidal behavior. Therefore it is important that physicians, patients and their families are informed about the potential risk of the emotional and psychiatric disturbances that can occur during alfa-interferon therapy. PMID- 7989717 TI - A clinicopathologic study of chronic non-A, non-B (type C) hepatitis in Taiwan: comparison between posttransfusion and sporadic patients. AB - To elucidate the clinicopathological course and the role of hepatitis C virus in posttransfusion and sporadic chronic non-A, non-B hepatitis in Taiwan, we retrospectively studied 85 histologically confirmed patients with long-term follow up. Antibodies against hepatitis C virus (anti-HCV) by a second-generation assay were positive in 81% of the patients: 88% in the posttransfusion group and 76% in the sporadic group. Clinical manifestations were generally mild, and were noted in only half of the patients. During follow up, 33% (28 of 85 patients) had episodes of acute exacerbation of chronic liver disease and 24% (20 of 85) had normalized liver tests. Patients with normalized liver tests were usually anti HCV negative (55% vs. 8%, p < 0.001). In 34 patients who had had blood transfusions, initial liver biopsies revealed chronic active hepatitis in 41%, active cirrhosis in 6%, and inactive cirrhosis in 9%. Follow-up biopsies in eight patients in this group showed histological progression in three after an average of 40.6 months. In the 51 sporadically infected patients, initial work-up revealed chronic active hepatitis in 37%, active cirrhosis in 4%, and inactive cirrhosis in 14%. Among the nine who underwent repeated biopsies, only one (11%) had progression. Patients above age 40 displayed more severe histologic activity than those below 40 (p < 0.005). Three patients, all with cirrhosis, died of hepatocellular carcinoma 7 to 12 years after follow up. Further genotyping study of hepatitis C virus in 28 patients showed that type II virus was most predominant in Taiwan and histologic severity was similar among patients infected with different genotypes.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7989718 TI - Twelve-year follow-up study of hepatitis B immunization of Senegalese infants. AB - Numerous studies have documented the efficacy and safety of plasma-derived and recombinant hepatitis B vaccines. However, little is known about the long-term protection of hepatitis B vaccine, when anti-HBs declines to low or undetectable levels. This study reports results from a 9-12-year period follow up of infants immunized against hepatitis B in Senegal. At the end of the follow-up period anti HBs were detected in 81% of children who received a booster dose at school age and in 68% of those who did not. HBsAg was detected in 19% of infants from the control group compared to only 2% of immunized infants, corresponding to a protective efficacy of 88%. The results show that long-term protection against HBsAg carriage of hepatitis B vaccination is very high and that a booster dose at school age does not significantly increase this protection. PMID- 7989719 TI - Pathogenetic mechanisms of hepatocellular damage in chronic hepatitis C virus infection. PMID- 7989720 TI - Hepatoprotection by hydrophilic bile salts. PMID- 7989721 TI - Detection of HBs antigen in "anti-HBc alone" positive sera. AB - The immunoserological finding "anti-HBc alone" is often observed in defined groups of individuals, such as patients with inflammatory hepatopathies, patients on hemodialyses or with organ transplants, i.v. drug users and homosexuals, but it also occurs in up to 1% of Swiss blood-donors. In order to gain further information about whether "anti-HBc alone" reflects late immunity or points to an ongoing or a recently passed hepatitis B virus infection, 153 serum samples were tested for immune-complex-dissociated HBs-antigen, using acid treatment for complex dissociation. Of the samples tested 31% contained complexed HBsAg, the highest rates being found in individuals with hepatopathies (up to 80%), in i.v. drug users (up to 63%) and in hemodialysis patients (40%). The 153 sera were also tested for HBV-DNA by nested PCR. Sixty (39%) probes yielded positive results, comprising 29 (48%) of 60 sera with immune-complexed HBsAg but only 18 (19%) of 93 probes without complexed HBsAg. The results point to the possibility that at least some of the individuals with "anti-HBc alone" still have an ongoing HBV infection. PMID- 7989722 TI - Analysis of the hepatitis C virus genome in patients with anti-LKM-1 autoantibodies. AB - Hepatitis C virus genotypes have been characterized in 22 patients with anti-LKM 1 positive chronic hepatitis C. Following the Simmonds classification, 77% of patients were infected by hepatitis C virus genotype 1, 18% by genotype 2 and 5% by genotype 3, thus excluding the association of the autoimmune reaction with a particular viral type. Prevalences of genotype 1 and 2 were significantly different from those obtained in 79 patients with chronic hepatitis C who were negative for anti-LKM-1, as these were more rarely infected by genotype 1 and more frequently by genotype 2. Clinical findings of anti-LKM-1 positive patients were similar in all three groups. Sequence analysis of the amplified 5'UTR provided identification of peculiar and identical nucleotide substitutions in two out of four patients with genotype 2. The analysis of the secondary structure of this region showed that the observed nucleotide mutations increased the stability of the stem formed in this position. PMID- 7989723 TI - Alpha interferon therapy in thrombocytopenia associated with hepatitis C virus infection. PMID- 7989724 TI - Long-term response to interferon-alfa 2b re-treatment in chronic hepatitis C. PMID- 7989725 TI - Isolation rooms for TB control. PMID- 7989726 TI - Isolation rooms for TB control. PMID- 7989727 TI - Sound bites, Socrates, and science. PMID- 7989728 TI - International comparison of results of infection surveillance: The Netherlands versus Belgium. AB - OBJECTIVE: To explore the potential benefit of comparing results from two national surveillance networks. DESIGN: Two prospective multicenter cohort studies of surgical wound infections (SWI). SETTING: Thirty-five and 62 acute care hospitals in The Netherlands (NL) and Belgium (B), respectively, from October 1, 1991, to June 30, 1992. RESULTS: The participation was equivalent in the two countries: 27% (NL) and 28% (B) of all acute-care hospitals. Marked differences emerged between the Dutch and Belgian crude infection rates and the specific rates by wound class and other risk factors. Because the case-mix in the countries is quite different, comparisons can be made only by specific surgical category. The results for inguinal hernia repair and for appendectomy are compared as an example. In herniorrhaphies, the difference in infection rate (0.4% [NL] versus 1.2% [B]) is not explained by differences in the distribution of risk factors. The shorter hospital stay in The Netherlands (4 days [NL] versus 6 days [B]), the more effective postdischarge surveillance in Belgium, and the fact that more than two thirds of the detected infections occurred after the first postoperative week probably can account for most of the difference. There was a striking difference in prophylaxis use (3.7% [NL] versus 41.9% [B]). In appendectomies, the Dutch patient population shows on average a higher risk profile, and surgery is urgent much more often in The Netherlands (78.3%) than in Belgium (49.2%). The infection rate is higher in The Netherlands, especially among the patients without prophylaxis, which again is employed less frequently there. CONCLUSION: We conclude that international comparisons yield interesting insights regarding quality of care, reaching beyond the field of nosocomial infection prevention. This is an argument in favor of more harmonization between surveillance networks. PMID- 7989729 TI - Improving hepatitis B vaccination rates among surgeons. AB - To improve hepatitis B vaccination among surgeons at our medical center, we instituted a program by which the surgeons were updated regarding vaccine safety and efficacy, and the cost of the vaccine and its administration at "strategic" locations was underwritten by the hospital. The rate of hepatitis B vaccination among surgeons increased from 62% to 89% based on pre- and postintervention surveys. PMID- 7989730 TI - Contaminated disinfectants in health clinics in Ilorin, Nigeria. AB - Five of 18 samples of working dilutions of disinfectants used in the University of Ilorin Teaching Hospital, the University Clinic, and three other urban medical centers were found to be contaminated with bacteria. The results confirmed that disinfectants in storage support the growth of infectious agents, underlining the need to use fresh preparations of disinfectants. PMID- 7989731 TI - Comparative risk of bloodstream infection in organ transplant recipients. AB - To determine relative rates and sources of nosocomial bloodstream infection in solid organ transplant recipients, concurrently collected data on 277 consecutive patients were reviewed. Twenty-eight patients developed 40 infections. Liver recipients experienced a higher rate (28%) than either kidney (5%) or heart, heart-lung (10%). Primary infections (60% overall) caused by gram-positive bacteria (59% overall) predominated at all three sites. PMID- 7989732 TI - Canada announces campaign to inform former transfusion recipients of HIV risks. PMID- 7989733 TI - Guideline for prevention of nosocomial pneumonia. The Hospital Infection Control Practices Advisory Committee, Centers for Disease Control and Prevention. PMID- 7989735 TI - Telemedicine changing practice of medicine. PMID- 7989734 TI - Women urged to play role in organized medicine. Interview by Bob Carlson. PMID- 7989736 TI - Stark outlook for physician self-referrals. PMID- 7989737 TI - Case study analysis of physician hospital organizations. PMID- 7989738 TI - Institutional ethics committees in Indiana: organization, structure and function. PMID- 7989739 TI - Choosing a practice management consultant. PMID- 7989740 TI - Physician serves as advocate for abused. PMID- 7989741 TI - A one-year review of the Eye Injury Registry of Indiana. AB - In the first year of operation, the Eye Injury Registry of Indiana collected data on 171 severe eye injuries and categorized them according to the circumstances of the injury, severity of tissue disruption and visual function. Many preventable causes of injury were documented. By understanding the contributors of accidental injury, prevention strategies can be implemented. This collaborative project should continue to provide useful information specific to Indiana concerning the root causes of eye injury. PMID- 7989742 TI - Developmental ages of the thymic epithelium and of the T cell precursors together determine the proportions of peripheral CD4+ cells. AB - In earlier studies on chimeric animals, we found that fetal thymocytes produced peripheral T lymphocyte populations depleted of CD4+ cells. This occurred whether the fetal thymocytes matured in the presence of adult or fetal thymic stromal cells. In contrast, fetal liver cells that differentiated in the adult thymus generated normal proportions of peripheral CD4+ cells. Because fetal liver cells are thought to be the immediate precursors to fetal thymocytes, we proposed that fetal thymic stroma would modulate the differentiation of fetal liver cells; specifically, that fetal liver cells maturing in the fetal thymus would resemble fetal thymocytes and produce low levels of peripheral CD4+ cells. To test this hypothesis, fetal thymic lobes were colonized in vitro with fetal liver cells and subsequently transplanted in vivo to Thy-1 congenic hosts. Under these conditions, fetal liver cells produced reduced proportions of CD4+ peripheral progeny. The under-representation of CD4+ peripheral T cells was apparently governed by the thymic epithelium because similar results were obtained with 2 deoxyguanosine-treated fetal thymuses colonized by fetal liver cells. In contrast, adult bone marrow cells made normal levels of CD4+ peripheral T cells whether maturation occurred in the fetal or the adult thymus. Thus, pre-T cells (fetal liver or adult bone marrow) lose the capacity to respond to fetal thymic stromal cells during development. These results indicate that the proportions of CD4+ cells in peripheral tissues are regulated by a combination of the developmental ages of the T cell precursors and the thymic stromal environment. PMID- 7989744 TI - Antigen presentation and assembly by mouse I-Ak class II molecules in human APC containing deleted or mutated HLA DM genes. AB - The behavior of mouse I-Ak molecules was studied in the human Ag presentation mutants T2 and 9.5.3, which contain deleted or mutated HLA DM genes. HLA class II molecules expressed by these APC are defective in presentation of native Ag and are mostly complexed with class II-associated invariant chain peptides (CLIP). In contrast to human class II molecules, a significant proportion of mouse I-Ak molecules expressed in T2 and 9.5.3 were associated with antigenic peptides, indicating that I-Ak/peptide assembly is possible in the absence of the Dm proteins. Thus, the presentation of determinants derived from hen egg lysozyme (HEL), keyhole limpet hemocyanin, and conalbumin was normal in 9.5.3Ak and a conalbumin determinant was presented normally by T2.Ak. However, the keyhole limpet hemocyanin determinant was not presented by T2.Ak, and HEL46-61 was only presented at a low level by these APC. SDS-stable, dimeric I-Ak molecules were expressed by both T2.Ak and 9.5.3Ak and formed late in their intracellular transport. Presentation of HEL46-61 was partially inhibited by disrupting vacuolar acidification in 9.5.3Ak, consistent with I-Ak/peptide assembly in a post-Golgi endosomal compartment. Accordingly, Dm is not an obligatory requirement for MHC class II/peptide assembly. We propose that Dm influences the displacement of CLIP from recently synthesized class II molecules, a process that is likely to be less critical for I-Ak because of its low affinity for CLIP. PMID- 7989743 TI - IL-2 can support growth of CD8+ T cells but not CD4+ T cells of human IL-2 receptor beta-chain transgenic mice. AB - We have generated transgenic mice expressing the human (h) IL-2R beta-chain on lymphoid cells under the control of the mouse H-2Kd promoter. Spleen cells and thymocytes of the transgenic mice were cultured in the presence of 5 nM hIL-2. After a 10-day culture, the expanded populations were analyzed by flow cytometry and shown to be composed of CD8+ T cells and gamma delta T cells. Surprisingly, CD4+ T cells of the transgenic mice did not proliferate in response to hIL-2, although the CD4+ T cells expressed the transgenic hIL-2R beta-chain as well as the endogenous gamma-chain on their surface and bound 125I-labeled IL-2. When CD4+ T cells of the transgenic mice were stimulated with anti-CD3 mAb, the CD4+ T cells proliferated in response to hIL-2. These findings suggest that CD4+ T cells may require another triggering signal to respond to IL-2 even when IL-2Rs are expressed. By contrast, CD8+ T cells and gamma delta T cells respond to IL-2 as long as IL-2Rs are expressed. PMID- 7989746 TI - Antigen-presenting function of human endothelial cells. Direct activation of resting CD8 T cells. AB - We characterized the response of resting human CD8 T cells to allogeneic endothelial cells (EC). Both resting and IFN-gamma-pretreated EC stimulate similar CD8 T cell proliferative responses (peak, day 5 to 6), whereas only IFN gamma-pretreated EC stimulate CD4 T cells. The response increases with increasing numbers of CD8 T cells from 25,000 to 400,000/well. The proliferation of CD8 T cells is inhibited by mAbs reactive with CD8 or HLA-A and -B molecules but not with CD4 or HLA-DR. mAb blocking studies show a role for CD2, LFA-3, and CD59, but not for intercellular adhesion molecule-1, intercellular adhesion molecule-2, very late activation Ag-4, vascular cell adhesion molecule-1, CD28, or CD28 ligand, as costimulatory molecules. The stimulation of resting CD8 T cells by EC causes secretion of IL-2 and IFN-gamma but not IL-4. Both proliferation and IFN gamma secretion are inhibited by mAb to the IL-2R alpha subunit (CD25). Limiting dilution analysis suggests that approximately 1 in 20,000 resting CD8 T cells secrete IL-2 in response to allogeneic EC. EC stimulate greater than 1 in 10,000 CD8/CD45RO+ cells but fewer than 1 in 40,000 CD8/CD45RA+ cells, which indicates that primarily memory CD8 T cells respond to EC. Coculturing CD8 cells with EC stimulates a sufficient level of endothelial class II MHC expression to subsequently support a CD4 T cell proliferative response. The ability of memory CD8 T cells to proliferate against allogeneic EC, a nonclassical APC, and their ability to stimulate EC may contribute to the initiation of vascularized organ graft rejection. PMID- 7989745 TI - Differential regulation of proto-oncogenes c-jun and c-fos in T lymphocytes activated through CD28. AB - The T cell surface molecule CD28 binds to ligands on accessory cells and APCs, playing an important costimulatory role in the response of T cells to Ags. Our knowledge of the intracellular signaling pathways coupled to this receptor is incomplete. In addition to activation of phospholipase C gamma 1, ligation of this receptor also seems to activate a calcium-independent, CD28-specific pathway. In this paper, we report that cross-linking of CD28 (but not CD2, CD5, LFA-1, or CD7) leads to an elevation of c-jun mRNA, with only minimal activation of c-fos expression. CD28-dependent induction of c-jun expression requires protein tyrosine kinase activity, but does not depend on activation of a phorbol ester-responsive protein kinase C or elevation of cytosolic calcium. Furthermore, CD28-dependent elevation of c-jun mRNA does not appear to be mediated at the level of mRNA stability. A mechanism is suggested whereby expression of c-jun and junB, in the absence of members of the fos family, can prevent inappropriate activation of T cells caused by ligation of CD28 in the absence of a specific antigenic stimulus. PMID- 7989747 TI - CD27 is a signal-transducing molecule involved in CD45RA+ naive T cell costimulation. AB - CD27 is a 120-kDa transmembrane homodimeric molecule expressed on the majority of T cells, B cells, and NK cells that belongs to the TNFR/nerve growth factor receptor family. The interaction between CD27 and its ligand, CD70, is thought to play an important role in T cell activation. In this paper we have examined the signal-transducing potential of CD27 in T cell costimulation. Anti-CD27 mAb, anti 1A4, induced substantial proliferation of peripheral blood T cells in the presence of a suboptimal dose of PMA, phytohemagglutinin, anti-CD2, or anti-CD3 together with a second Ab to cross-link the CD27 molecule. This T cell proliferation was also observed by using CD70 transfectant cells. CD27 cross linking maximally induced proliferation of CD45RA+CD4 T cells but only slightly induced proliferation of CD45RO+CD4 T cells. CD27-mediated T cell proliferation did not seem to be dependent on the IL-2/IL-2R system because no detectable level of IL-2 was secreted, and only a partial inhibition was observed with anti-IL-2 and anti-IL-2R Abs. Furthermore, an increase in intracellular Ca2+ was observed in PMA-treated T cells when the CD27 molecule was cross-linked. More importantly, CD27 ligation induced protein tyrosine phosphorylation, especially 70 kDa of cellular substrate, including ZAP-70, in T cells. Herbimycin A, a protein tyrosine kinase inhibitor, and staurosporine, a protein kinase C inhibitor, blocked T cell proliferation induced by CD27 ligation, suggesting the possibility that the activation of protein tyrosine kinase and protein kinase C is required for CD27-mediated T cell costimulation. These results clearly demonstrate that the CD27/CD70 interaction induces costimulatory signals in T cells, especially CD45RA+ naive T cells, indicating that CD27 serves as a T cell signal-transducing molecule. PMID- 7989748 TI - Platelet-activating factor induces the tyrosine phosphorylation and activation of phospholipase C-gamma 1, Fyn and Lyn kinases, and phosphatidylinositol 3-kinase in a human B cell line. AB - Platelet-activating factor (PAF) is a versatile lipid mediator of inflammation in a variety of biologic systems. We have previously reported that one of the earliest events in the signal transduction pathway of PAF in a human B lymphoblastoid cell line was the induction of tyrosine kinase activity concomitant with the activation of phospholipase C (PLC). We now demonstrate the occurrence of multiple tyrosine phosphorylation-dependent events which follow the interaction of PAF with its receptor on B cells. Anti-phosphotyrosine immunoprecipitates from lysates of PAF-stimulated cells, when fractionated by SDS PAGE and analyzed by Western blotting with anti-PLC-gamma 1, showed that maximal tyrosine phosphorylation of this enzyme occurred within 2 min of stimulation. This phenomenon was verified by immunoprecipitating with anti-PLC-gamma 1 and subsequently probing with anti-phosphotyrosine. Immunoprecipitation of the tyrosine kinases, Fyn and Lyn, from PAF-stimulated cells, and use of these immunoprecipitates in kinase assays established that the activation of both kinases also occurred within the first 2 min of stimulation with phosphorylation occurring on their tyrosine residues. Additionally, we also provide evidence for the tyrosine phosphorylation of the p85 subunit of phosphatidylinositol 3-kinase (PtdIns 3-kinase) and activation of this kinase by PAF in a dose-dependent manner, maximal activation occurring within 10 min post-stimulation. We have thus demonstrated that the activation of tyrosine kinases is an important proximate step in PAF-mediated signal transduction in B cells, leading to tyrosine phosphorylation and activation of PLC-gamma 1, Fyn and Lyn kinases, and PtdIns 3 kinase. PMID- 7989749 TI - Tyrosine phosphorylation of VCP, the mammalian homologue of the Saccharomyces cerevisiae CDC48 protein, is unusually sensitive to stimulation by sodium vanadate and hydrogen peroxide. AB - A mAb produced by immunization of mice with tyrosine-phosphorylated proteins from activated B lymphocytes was found to recognize valosin-containing protein (VCP). VCP is the mammalian homologue of the Saccharomyces cerevisiae CDC48 protein and has localized regions of sequence identity with the yeast Sec18 and Pas1 proteins and the mammalian NSF protein, all of which are important in intracellular vesicular traffic or formation. VCP was found to be constitutively phosphorylated on tyrosine in Rous sarcoma virus-transformed fibroblasts. Phosphorylation of VCP on tyrosine was stimulated only modestly during activation of B lymphocytes by ligation of membrane Ig. In contrast, treatment of B cells with either H2O2 or a combination of H2O2 and Na3VO4 greatly increased tyrosine phosphorylation of VCP. These results may suggest that under normal conditions tyrosine phosphorylation of VCP has a rapid turnover and that it can be detected easily only when dephosphorylation is inhibited by artificial means. PMID- 7989750 TI - H-2 allele-specific protection from NK cell lysis in vitro for lymphoblasts but not tumor targets. Protection mediated by alpha 1/alpha 2 domains. AB - In vivo murine NK cells are known to mediate graft rejection in allogenic as well as in "F1 anti-parental" situations. We have studied an in vitro system based on rIL-2-activated spleen cells and Con A lymphoblast targets in relation to the genetics of F1 hybrid resistance and NK cell activity. We demonstrate that NK cells in this in vitro model are regulated by MHC class I genes in an allele specific manner at the level of the effector and the target. Using rIL-2 activated effector cells from nude C57BL/6 (B6) and BALB/c mice, we observed no killing of MHC syngeneic lymphoblasts. However, B6 as well as BALB/c lymphoblasts were killed by effector cells from allogeneic nude mice as well as by cells from (BALB/c x B6)F1 hybrids. Experiments that used D8 mice (which carry an H-2Dd transgene on B6 background) and beta 2-m-/- mice demonstrated a direct role for MHC class I molecules at the effector as well as at the target cell level: H-2Dd transgenic effector cells with the typical NK phenotype 3A4+/CD8- killed B6 blasts, but expression of the corresponding H-2Dd transgene in the target lymphoblasts protected them from killing. By using transgenic mice carrying exon shuffled MHC class I transgenes, the protective effect of the H-2Dd molecule was mapped to the alpha 1/alpha 2 domains. MHC class I-deficient lymphoblasts from beta 2-m-/- mice were killed by effectors from all strains of mice, including those matched for MHC. The H-2 class I allele-specific protection in this in vitro assay was observed for lymphoblasts but not for tumor cells, despite the fact that these tumor cells are protected in an allele-specific manner in vivo. PMID- 7989751 TI - TCR selection and allelic exclusion in RAG transgenic mice that exhibit abnormal T cell localization in lymph nodes and lymphatics. AB - RAG-1 and RAG-2 are developmentally regulated genes that are essential for V(D)J recombination and lymphocyte development. Expression of RAG-1 and RAG-2 by thymocytes is normally limited to cells that have not completed selection. We have previously documented that persistent expression of the recombinase activating genes (RAG) in transgenic mice results in aberrant thymic development, altered lymphatic microanatomy, and a profound immunodeficiency. Here we further document the pathologic changes found in TG.RAG-1,2 mice and examine the role of TCR recombination and positive and negative thymic selection, as well as allelic exclusion, in the etiology of the phenotype. We find that neither selection nor TCR allelic exclusion can be overcome by transgenic expression RAG-1 and RAG-2 under the control of an lck promoter. PMID- 7989752 TI - CD43 (S7) expression identifies peripheral B cell subsets. AB - CD43 (leukosialin) expression has previously been demonstrated on the surface of developing B cells in mouse bone marrow and on plasma cells induced in vitro, but not on peripheral B cells in spleen. Here we show that CD43, as recognized by mAb S7, is indeed expressed on a small population of splenic B cells. Flow cytometric phenotyping of normal mice and radiation chimeras reveals that CD43/S7 is expressed on virtually all (> 90 to 95%) splenic B-1 cells and the majority of peritoneal B-1 cells, but not on conventional B cells. The expression of CD43/S7, in conjunction with other cell surface markers, clearly distinguishes B-1 cells from follicular, marginal zone, and immature B cells in the unstimulated adult spleen and permits further phenotyping of these subsets. The phenotype of splenic and peritoneal B-1 cells in normal BALB/c and BAB/25 mice is essentially identical with the exception that all peritoneal B-1 cells express CD11b (Mac-1) and some lack CD43/S7 and heat stable Ag (as detected by the mAb 53-10) expression. Although splenic B-1, marginal zone, and immature B cells share many phenotypic characteristics, these studies show that, in addition to CD43, they differ with respect to the expression levels of a variety of Ags including heat stable Ag, B220, and the B cell activation Ag B7. PMID- 7989753 TI - A soluble form of the HLA-G antigen is encoded by a messenger ribonucleic acid containing intron 4. AB - The HLA-G primary transcript is alternatively spliced to yield mRNAs encoding three alternative membrane bound proteins. In addition to these forms, a soluble HLA-G protein has been described which is not encoded directly by any of the three alternative mRNAs. To explain the process which might lead to the expression of a soluble HLA-G Ag, we investigated the potential roles proteolytic processing and additional alternative splicing of HLA-G RNA might play. By generating transfected cells with HLA-G cDNA expression driven by a retroviral promoter, it was possible to rule out proteolytic processing of the membrane bound HLA-G as a mechanism of generating soluble HLA-G, resulting in our focus on alternative splicing as an explanation. Analysis of PCR-amplified cDNA revealed a relatively abundant transcript present in all samples examined which consisted of the full length HLA-G mRNA sequence interrupted by intron 4 sequence. The open reading frame in this mRNA continues into intron 4 terminating 21 amino acids after the alpha 3 domain, thus excluding the transmembrane encoding region and yielding a protein with a highly charged carboxyl terminus. Transfection of the intron 4 containing cDNA, inserted into a retroviral expression vector, into LCL .221 followed by comparison of the class I protein to native soluble G by two dimensional isoelectric focusing/SDS-PAGE analysis, demonstrated this message encoded the soluble HLA-G protein. In addition, a similar intron containing message derived from the HLA-G2 mRNA was found, suggesting the existence of a soluble form of this alternative HLA-G protein. These findings are discussed in relation to other soluble class I molecules and with regard to potential functions of the soluble HLA-G Ag. PMID- 7989754 TI - Novel allele-specific, post-translational reduction in HLA class I surface expression in a mutant human B cell line. AB - Human B cell line .220 has a novel defect in HLA class I cell surface expression. Mutant .220 was derived from .184TGr, from which both copies of HLA-A and -B are deleted, and has less surface HLA-C than .184TGr. Transfer of class I genes into .220 revealed allele-specific reductions in surface expression: HLA-A1 and -B8 were 1 to 21% of normal; HLA-A11, -A24, and -B5 were moderately reduced; and HLA A2, -A3, and -B7 were reduced little, if at all. Class I mRNA in .220(A1) and .220(B8) transferents is normal in size and at least normal in quantity. Surface expression of class I molecules was restored by fusing .220 transferents with mutant .174, which lacks the TAP-1 and -2 genes needed for transport of class I binding peptides. Fusion of .220(A1) cells with beta 2-microglobulin-deficient Daudi cells also fully restored surface expression of class I molecules encoded by both parental cells, indicating beta 2-microglobulin is functional in .220. Pulse-chase experiments showed transgene-encoded HLA-A1 and -B8 alpha-chains are made in apparently normal amounts and associate with beta 2-microglobulin in .220. However, post-translational processing of the HLA-A1 and -B8 molecules is retarded in or before the Golgi apparatus, and immunoprecipitable HLA-A1 molecules disappear after their synthesis. The effects of these abnormalities on surface expression of class I molecules were reversed by incubating .220(A1) and .220(B8) cells at 21 degrees C, which greatly increased the amounts of cell surface HLA-A1 and -B8. PMID- 7989755 TI - Regulation of the human IgE receptor (Fc epsilon RII/CD23) by EBV. Localization of an intron EBV-responsive enhancer and characterization of its cognate GC-box binding factors. AB - EBV infection of human B lymphocytes induces expression of the low affinity IgE receptor, Fc epsilon RII/CD23. CD23 is constitutively expressed in EBV immortalized B cells and may play an essential role in immortalization. We previously explored the regulation of CD23 by EBV, showing that induction results from transcriptional activation that is mediated, in part, by an EBV-responsive transcriptional regulatory element in the 5' region of CD23 (-229 to +305 relative to the type a promoter). We now report the localization of the regulatory element and characterization of its cognate DNA-binding proteins. Reporter gene assays in EBV-positive and -negative lines localized a functional EBV-responsive enhancer to a 37-bp fragment (+248 to +284) that contains a GC rich sequence (GC box) within intron I of type a CD23. This fragment was shown by mobility shift assays to specifically bind nuclear protein(s) from EBV-positive lines, but not EBV-negative lines. Mutation of the GC box resulted in a loss of protein-binding activity, implicating involvement of a GC box-binding protein in the DNA/protein interaction. Supershift assays suggested that the ubiquitous GC box-binding transcription factor, Sp1, is not a part of the complex, and UV crosslinking studies demonstrated that the DNA/protein complex contains at least two proteins that differ in size from other known GC box-binding proteins. Binding of these proteins to the enhancer element requires phosphorylation, because phosphatase treatment of nuclear extracts abolished formation of the DNA/protein complex. These studies reveal the presence of an EBV-responsive enhancer element in intron I of type a CD23 and implicate a GC box-binding transcription factor in the activation of CD23 by EBV. PMID- 7989756 TI - One gene encodes the heavy chains for three different forms of IgY in the duck. AB - IgY, the major Ab of the duck (Anas platyrhynchos), exists in two secreted forms and a transmembrane (TM) form. To investigate the genetic relationships of the multiple IgY we cloned the gene encoding the IgY (upsilon) heavy chains. The heavy chain of the smaller (5.7S) IgY, which lacks the third and fourth constant domains, results from the use of a unique terminal exon found in the intron between the second and third C region exons. Alternate pre-mRNA processing pathways also produce a full-length upsilon-chain and a TM form, each having four C region domains. Although the number of secretory exons and the inferred positions of intramolecular disulfide bonds indicate structural similarity between IgY and IgE, the TM exons of duck IgY share high sequence identity and a similar pattern of RNA processing with those of IgG. These results suggest that IgG and IgE may have diverged from an ancestral molecule resembling IgY. PMID- 7989757 TI - An Ig heavy chain enhancer of the channel catfish Ictalurus punctatus: evolutionary conservation of function but not structure. AB - The teleost fishes are among the earliest evolutionary lineages to have an Ig heavy chain (IgH) locus whose organization approximates that of mammals. To understand transcriptional control of the IgH locus in a teleost fish and to gain insight into the evolution of the control elements, the enhancer activity in the IgH locus of the channel catfish, Ictalurus punctatus, was investigated. Segments of the locus extending from upstream of the proximal JH gene to 2.5 kb downstream of the second transmembrane (TM2) exon of the mu gene were tested in transient transfection expression assays in murine myeloma and T cell lines, and in catfish B lymphoblastoid, monocyte-like, and putative T cell lines. In marked contrast to mammals, no enhancer activity was observed in the catfish JH to C mu intron, but strong enhancer activity (approaching that of the murine IgH intronic enhancer) was identified in a 1.8-kb segment that included the TM2 exon. This catfish enhancer was active in a B lineage-specific manner in both catfish and murine cells. It was not localized in a small core region, but appeared to contain multiple, dispersed cooperative elements rich in octamer- and mu E5-related motifs. Although the catfish IgH enhancer shares functional characteristics with the mammalian IgH intronic and 3' enhancers, its unusual organization does not permit any obvious inferences concerning evolutionary relationships between the catfish enhancer and any one of the murine IgH enhancers. PMID- 7989758 TI - Individual effects of the DR11-variable beta-chain residues 67, 71, and 86 upon DR(alpha,beta 1*1101)-restricted, peptide-specific T cell proliferation. AB - The four members of the HLA-DR11 family of class II molecules vary only by three or fewer amino acids via dimorphisms among DR beta-chain residues 67, 71, and 86. However, they differ markedly in their abilities to induce proliferation of DR(alpha,beta 1*1101)-restricted, peptide-specific T cell clones. To dissect which DR11-variable residues, individually and in combination, mediate these functional differences, we used as APC transfectants expressing DR molecules with one of all possible permutations of DR11-variable sequences, including the four DR11 family members, and four additional DR11 variant mutants. The abilities of the wild-type or mutant molecules to present two distinct influenza peptide Ags, HA307-19 and HA128-45, to T cells was assessed in in vitro T cell proliferation assays. Of the naturally dimorphic DR11 positions, residue beta 71 variation significantly influenced the ability of DR11 molecules to present both peptides to DR(alpha,beta 1*1101)-restricted T cells. Residue beta 86 variation had relatively less influence than reported in several other DR and peptide systems. Residue beta 67 variation usually appeared irrelevant to T cell proliferation, but in two mutants led to unexpected T cell proliferation independent of nominal peptide Ag. Peptide binding, assessed by flow cytometry, was not found to be altered by any mutations that disrupted DR(alpha,beta 1*1101)-like presentation. These data indicate that residue beta 71 exerts a central role in influencing the functional differences among DR11 molecules, whereas the widely studied dimorphism of residue beta 86 is not as generally influential in DR11 as in other alleles. PMID- 7989759 TI - Octamer factors exert a dual effect on the IL-2 and IL-4 promoters. AB - The promoters of IL-2 and IL-4 genes contain multiple binding sites for octamer factors. In peripheral T lymphocytes and several T cell lines, both the ubiquitous Oct factor Oct-1 and the lymphocyte-specific factor Oct-2 are expressed and bind to the IL-2 and IL-4 promoters. Prominent octamer binding sites of IL-2 and IL-4 promoters are their upstream promoter sites (UPS) which share 14 identical nucleotides. Multiple copies of the IL-2 and IL-4 UPS act as inducible enhancers in T cells, and their induction is inhibited by the immunosuppressant cyclosporin A (CsA). Closely linked to the octamer site, the IL 2 UPS contains a non-canonical AP-1 binding (TRE) site, and mutation in either site to a non-functional factor binding site impairs the induction of the IL-2 promoter. The binding of AP-1 and octamer factors to the IL-2 UPS DNA overlaps, and the tight association and functional cooperation of octamer with AP-1 factors is of crucial importance for the inducible IL-2 UPS activity. Introduction of five or ten spacer nucleotides between both IL-2 UPS sites results in a drastic reduction of inducible UPS activity, both in the loss of suppression by CsA and stimulation by the Ca(2+)-dependent phosphatase calcineurin. Within the IL-4 UPS the Oct and TRE-like motifs are separated by a binding site of nuclear factor of activated T cells (NF-AT). This site shares nine out of ten bp with an IL-2 NF-AT site. The strong binding of NF-ATp to the IL-4 UPS site suppresses the simultaneous binding of Oct factors to the IL-4 UPS. Because the two other Oct binding sites of IL-4 promoter show a similar sequence configuration, the binding of NF-AT seems to prevent the simultaneous binding of Oct factors to the IL-4 promoter. By contrast, both classes of factors bind simultaneously to the IL-2 promoter, and their tight association with AP-1 enhances the IL-2 promoter activity. PMID- 7989760 TI - Genomic organization of mouse and human Bruton's agammaglobulinemia tyrosine kinase (Btk) loci. AB - Btk is a cytoplasmic protein tyrosine kinase (PTK) that has been directly implicated in the pathogenesis of X-linked agammaglobulinaemia (XLA) in humans and X-linked immunodeficiency (Xid) in mice. We have isolated phage and cosmid clones that allowed us to deduce the genomic structure of mouse and human Btk loci. The mouse and human genes are contained within genomic regions that span approximately 43.5 kb and 37.5 kb, respectively. Both loci contain 18 coding exons ranging between 55 and 560 bp in size with introns ranging in size from 164 bp to approximately 9 kb. The 5'-untranslated regions are encoded by single exons located approximately 9 kb upstream of the first coding exon. Exon 18 encodes for the last 23 carboxyl-terminal amino acids and the entire 3'-untranslated region. The location of intron/exon boundaries in the catalytic domains of the mouse and human Btk loci differs from that found in other described sub-families of intracellular PTKs, namely that of Src, Fes/Fer, Csk, and Abl/Arg. This observation is consistent with the classification of Btk together with the recently characterized kinases, Tec and Itk, into a separate sub-family of cytoplasmic PTKs. Putative transcription initiation sites in the mouse and human Btk loci have been determined by using the rapid amplification of cDNA ends assay. Similar to many other PTK specific genes, the putative Btk promoters lack obvious TATAA and CAAAT motifs. Putative initiator elements and potential binding sites for Ets (PEA-3), zeste, and PuF transcription factors are located within the 300 bp which are located upstream of the major transcription start site in both species. These sequences can mediate promoter activity when placed upstream of a promotorless chloramphenicol acetyl transferase reporter gene in an orientation-dependent manner. The present analysis will significantly facilitate the mutational analyses of patients with XLA and the further characterization of the function and regulation of the Btk molecule. PMID- 7989761 TI - Expressed swine VH genes belong to a small VH gene family homologous to human VHIII. AB - The sequences of 34 swine H chain V-regions expressed with either IgG, IgA, or IgM C regions in adult swine and newborn piglets are described and compared. Sixteen of these V-regions were cloned by using a specific leader primer whereas 18 were cloned by anchored PCR. According to the operational criterion of VH family classification, i.e., > 80% DNA sequence similarity, all sequences belong to a homogeneous VH gene family. A total of 31 additional VH-bearing C mu clones obtained by anchored PCR from colostrum-deprived newborn piglets hybridized equally with a probe for C mu and a pan-VH probe. When the consensus sequence of the expressed swine VH genes were compared with those of VH gene for humans (VHI, II, III), mouse (VHI, II, III), rabbit, and chicken, swine VH genes seem to have common ancestry with the human VHIII family, rabbit VH genes, and the single functional VH gene of the chicken. The leader peptides of all clones obtained by anchored PCR showed < 1% variability, and the deduced amino acid sequences from aa4 to aa25 in all 34 clones are identical. Framework (FR)1 and FR2 are conserved whereas FR3 shows greater variability. A total of 23 of 30 JH sequences were identical, suggesting preferential use of one JH. This frequent, putative JH sequence is not similar to any JH gene in humans. Identical genomic Southern hybridization patterns, each with 13 bands of differing intensity and regardless of stringency, were obtained when either a leader or a pan-specific VH probe was used. Analyses of individual genomic bands by single strand conformational polymorphism and sequence analysis suggest that the number of VHIII-related genes in the swine genome is < 20. PMID- 7989762 TI - HLA-G polymorphisms in African Americans. AB - HLA-G is a class I MHC gene most notable for its restricted tissue distribution. The unique expression of this gene in extravillous cytotrophoblast at the maternal-fetal interface suggests that HLA-G plays a critical role in human pregnancy. Previous studies have reported that HLA-G has a limited repertoire of rare alleles, unlike the classical class I alleles, which are among the most polymorphic human genes. To determine the full extent of sequence variation in this gene, we examined the nucleotide variation in the first six exons of this gene in 45 healthy African American persons. By using sensitive techniques that detect > 95% of nucleotide substitutions, we detected two sequence variations in the alpha-1 domain (exon 2) and 24 sequence variations in the alpha-2 domain (exon 3) that result in amino acid substitutions. These data indicate that HLA-G is potentially capable of presenting a wide variety of peptides and of eliciting an allogeneic response, similar to the classical class I HLA genes. PMID- 7989763 TI - Candidacidal mechanisms in the human neonate. Impaired IFN-gamma activation of macrophages in newborn infants. AB - We studied the interaction between Candida albicans and mononuclear phagocytes derived from cord blood. In the presence of normal serum, the extent of phagocytosis and killing of candida by monocyte-derived macrophages was equivalent for newborns and adults. In the absence of serum both phagocytosis and killing by macrophages were reduced by half, but cord and adult cells were still equivalent. Mannosylated BSA and mannan inhibited ingestion of unopsonized candida by macrophages, suggesting a role for the mannose receptor. Exposure of cord and adult macrophages to IFN-gamma (10-500 U/ml) gave quantitatively different results in Candida killing, as well as in release of superoxide anion (O2-). Maximal increase in these functions with adult macrophages was achieved with 100 U/ml IFN-gamma. No enhancement with cord macrophages could be detected after treatment with 100 U/ml, and at 500 U/ml there was still significantly lower killing and O2- release compared with adult cells. Defective up-regulation of O2- release was also present in cord monocytes exposed to IFN-gamma on day 0. Studies of the surface expression of IFN-gamma receptors using a "nonblocking" mAb against the IFN-gamma receptor revealed a comparable number of receptors on cord and adult monocytes. When blocking Abs were used, however, there was a three times higher number of positive cells in cord monocytes. Specific binding of 125I IFN-gamma to cord monocytes and macrophages was also higher compared with adult cells. These data suggest that neonatal macrophages have a normal capacity to ingest and kill both opsonized and unopsonized Candida but cannot be fully activated by IFN-gamma, a finding that could not be attributed to lower expression of IFN-gamma receptors on the neonatal cells. PMID- 7989764 TI - An efficient Th2-type memory follows CD8+ lymphocyte-driven and eosinophil mediated rejection of a spontaneous mouse mammary adenocarcinoma engineered to release IL-4. AB - A retroviral infection was used to introduce the cDNA coding for mouse IL-4 into the parental cells of a spontaneous adenocarcinoma of BALB/c mice (TS/A-pc). Four clones releasing between 5 to 40 U of IL-4 (10(5) cells) in 48 h culture were selected. The secretion of IL-4 does not affect their in vitro growth, whereas their ability to form tumor in vivo inversely correlates with the amount of IL-4 secreted. Although morphologic observation suggested that the rejection of clone D5.40 cells (releasing 40 U of IL-4) depends on eosinophil cytolysis, lymphocyte depletion experiments showed that this required CD8+ lymphocyte guidance. Mice that had rejected D5.40 cells were immune to a subsequent challenge with TS/A-pc. This memory rests on the interaction between noncytotoxic lymphocytes, eosinophils, and IgG1 and IgE anti-TS/A Abs. Comparison of these memory mechanisms with those elicited by IL-2 gene-transduced TS/A cells shows that the kind of cytokine released by the tumor cells determines the type of response. This Th2 memory seems to be more efficient in protecting against a subsequent challenge of TS/A-pc than the Th1-type memory elicited by IL-2 gene-transduced TS/A cells. PMID- 7989765 TI - IL-2-dependent NK cell responses discovered in virus-infected beta 2 microglobulin-deficient mice. AB - In vivo NK cell responses to lymphocytic choriomeningitis virus were studied in CD8+ T cell-deficient mice. On day 7 after infection, dramatically elevated splenic NK cell activities were observed in both beta 2-microglobulin-negative (beta 2-m-/-) mice deficient in CD8+ T cells and anti-CD8-treated C57BL/6 animals. The enhanced responses could be attributed to increased numbers of activated NK1.1+CD3- cells. The day 7 NK cell responses in beta 2-m-/- mice, but not in normal C57BL/6 animals, were cyclosporin A sensitive and coincided with IL 2 production and high affinity IL-2R expression on NK cells. Proof that IL-2 played an essential role in day 7 responses was provided by the observation that IL-2-/- x beta 2-m-/- mice lacked the late NK cell activation. Taken together, these results showed that NK cells can be activated and expanded by an IL-2 dependent pathway. Because these responses can only be measured in the absence of CD8+ T lymphocytes, an exciting model of networking between T and NK cells in response to viruses is postulated. PMID- 7989766 TI - Neutrophils migrate to delayed-type hypersensitivity reactions in joints, but not in skin. Mechanism is leukocyte function-associated antigen-1-/Mac-1-independent. AB - We have previously found that polymorphonuclear leukocyte (PMNL) migration to adjuvant arthritic joints of rats was only partially inhibited by mAbs to the adhesion molecules LFA-1 (CD11a/CD18) and Mac-1 (CD11b/CD18), suggesting that there is a CD11/CD18-independent mechanism for PMNL migration to inflamed joints. Adjuvant arthritis in rats is believed to be initiated by a T lymphocyte dependent immune response and maintained by proinflammatory cytokines such as IL 1 and TNF-alpha. Here we studied two types of joint inflammation: that induced by a delayed-type hypersensitivity (DTH) reaction in the joint and that induced by intra-articular (i.a.) injection of cytokines, to explore PMNL migration to inflamed joints and examine the role of CD18. 51Cr-labeled blood PMNL were used to measure PMNL migration in rats to inflammatory reactions in joints and compared with reactions in skin. A large number of PMNL migrated to the carpal and talar joints after i.a. injection of Mycobacterium purified protein derivative in sensitized animals to induce DTH, but there was minimal PMNL migration to this DTH reaction in the skin. This migration to the joints was not inhibited by mAbs to LFA-1 alone or mAbs to LFA-1 plus Mac-1 that almost completely inhibited PMNL accumulation in dermal inflammatory reactions induced by zymosan-activated serum (C5adesArg), endotoxin, IL-1 alpha, or TNF-alpha in the same rats. Intra-articular injection of the cytokines IL-1 alpha and TNF alpha, but not IFN-gamma, induced marked PMNL accumulation in the joints; this was strongly inhibited by the treatment of rats with anti-LFA-1 and anti-Mac-1. Thus, PMNL migrate to DTH induced in joints but not in skin, and this migration is CD18-independent, but migration to i.a. IL-1 alpha and TNF-alpha is largely CD18 dependent in both joints and skin. This suggests that both the joint microenvironment and the T cell dependence of the inflammatory reaction in the joint governs the mechanism of PMNL recruitment. PMID- 7989767 TI - Connective tissue-activating peptide III desensitizes chemokine receptors on neutrophils. Requirement for proteolytic formation of the neutrophil-activating peptide 2. AB - The connective tissue-activating peptide III (CTAP-III), which is released from activated platelets, represents an inactive precursor of the chemokine neutrophil activating peptide 2 (NAP-2). Leukocytes and leukocyte-derived proteases have been found to convert CTAP-III into NAP-2 by proteolytic cleavage at the N terminus. We demonstrate here that rapid and efficient formation of NAP-2 is mediated by neutrophil granulocytes (PMN) but not by monocytes or lymphocytes. However, as seen in a degranulation assay, neutrophils processing CTAP-III did not become activated by the generated NAP-2 and even exhibited decreased responsiveness to high doses of NAP-2 or IL-8, but not to FMLP. The desensitizing effect, being maximal already after 5 min of preincubation with CTAP-III, was not mediated through binding of the precursor to specific receptors but correlated with the rapid down-modulation of common NAP-2/IL-8 high affinity binding sites. A similar functional and receptor desensitization was observed in PMN pre-exposed to nonstimulatory doses of NAP-2. Specific inhibition of the CTAP-III-cleaving enzyme by the serine protease inhibitor aprotinin abrogated the CTAP-III, but not the NAP-2-mediated effects. Desensitization of PMN by CTAP-III was due to NAP-2 generated by proteolytic truncation of CTAP-III. Our results suggest that CTAP III may regulate PMN activation by protecting processing cells from premature activation. PMID- 7989768 TI - Transfection of vitamin D receptor cDNA into the monoblastoid cell line U937. The role of vitamin D3 in homotypic macrophage adhesion. AB - A 2-kB cDNA for the vitamin D receptor (VDR) was cloned in sense orientation into the plasmid pMEP4 (containing a cadmium-inducible metallothionein II promoter and a hygromycin-resistance selection gene) and transfected into monoblastoid U937 cells. The resultant cell line, DH39, expressed two species of VDR mRNA: 4.6-kb wild-type mRNA (present in native U937 cells or cells transfected with pMEP4 alone) and 2-kb transfected mRNA, which increased with cadmium treatment. Binding studies (using the active vitamin D metabolite, 1,25-dihydroxycholecalciferol (1,25-DHCC)) showed that DH39 cells contained five times more VDR per cell than controls, and ten times more after cadmium treatment. DH39 were sensitive to 1,25 DHCC: adding cadmium with 100 nM 1,25-DHCC for 72 h completely inhibited proliferation and induced concomitant differentiation. Unlike control cells, differentiation of DH39 by 1,25-DHCC led to homotypic cell-cell adhesion and formation of macrophage clusters. FACS analysis showed that 1,25-DHCC increased the number of cells expressing CD11b in both DH39 and controls, and the number of cells expressing CD11c in DH39. There was a quantitative increase in mean fluorescence intensity of expression of CD11a and CD18 in DH39. Northern blotting showed increased CD11a and CD18 mRNA in DH39. Ab inhibition of 1,25-DHCC-induced homotypic adhesion showed that CD11a/18 mediated the cell-cell clustering. CD50 expression was decreased on DH39, but the CD11a/18 ligand implicated was CD54. DH39 provides a model system not only for investigating the VDR role in 1,25-DHCC anti-proliferative effects, but also for regulation of homotypic macrophage adhesion mechanisms that are important in disease pathogenesis. PMID- 7989769 TI - A transcription factor with AP3-like binding specificity mediates gene regulation after an allergic triggering with IgE and Ag in mouse mast cells. AB - Mast cells are an important source of a number of lymphokines and chemokines primarily those released after challenge with the allergic trigger IgE and Ag. However, the mechanisms of lymphokine and chemokine gene activation in this cell type, as opposed to the mechanisms of activation in T cells, are poorly understood. As a model system, we addressed this issue in mast cells by using the recently cloned chemokine MARC gene, which belongs to the RANTES/sis gene family. After allergic stimulation, MARC induction is pronounced and mast cell specific. Northern blot analysis, in combination with two inhibitors, actinomycin D and cycloheximide, resulted in the formation of our initial hypothesis, which was that both transcriptional and post-transcriptional regulation are involved after stimulation through the Fc epsilon R. We performed a detailed promoter analysis of the cloned MARC gene by using transient assays of transfected reporter gene constructs. Thereby, two potential promoter regions were identified as being crucial for transcriptional stimulation. Additional fine mapping of the proximal element and subsequent electrophoretic mobility shift assays, combined with competitions of known transcription factor binding sites, identified one of the transcription factors in stimulated mast cells as an AP3 or AP3-like binding activity. PMID- 7989770 TI - Regulation of intestinal epithelial barrier function by TGF-beta 1. Evidence for its role in abrogating the effect of a T cell cytokine. AB - Maintenance of the integrity of the single-cell-thick intestinal epithelium as an in vivo barrier between environmental Ags and mucosal immunocytes is pivotal for health. The T cell cytokine IFN-gamma consistently disrupts this epithelial barrier in vitro, but the substances in mucosa that may be responsible for sustaining or enhancing barrier function have not been clearly identified. Therefore, we characterized the effect on the epithelial barrier of TGF-beta 1 and three prominent neuropeptides (VIP, substance P, somatostatin) by using a model system in which barrier function of a mature polar human colonic epithelial (T84) cell monolayer is reflected in 1) the electrical potential difference across the apical to basolateral surface of each cell, 2) the transmonolayer permeability to macromolecules such as horseradish peroxidase, and 3) lactate dehydrogenase release into the medium indicating epithelial cell cytolysis. Whereas T84 monolayers exposed to TGF-beta 1 alone demonstrated a modest increase in electrical resistance and barrier integrity, TGF-beta 1 showed a striking ability to reduce the capacity of IFN-gamma to disrupt epithelial barrier function. Characterization studies demonstrated that this TGF-beta 1 effect was prolonged (e.g., days) after a single exposure, progressive over the dose range 0.1 to 2.5 ng/ml, reversible with increased concentrations of IFN-gamma, and more pronounced when TGF-beta 1 exposure was to basolateral rather than to apical epithelial membranes. Macromolecular (horseradish peroxidase) penetration of epithelium was not simultaneously altered by TGF-beta 1 and epithelial cellular injury was minimal as gauged by lactate dehydrogenase release. Additional studies using a human pathogen demonstrated that TGF-beta 1 delayed and decreased the barrier disruption caused by exposure to Cryptosporidium parvum. TGF-beta 1 may be the first of a new class of cytokines that maintains and/or enhances barrier function of human enterocytes, in part by countering the effect of a T cell cytokine. PMID- 7989771 TI - Lipopolysaccharide induces activation of the Raf-1/MAP kinase pathway. A putative role for Raf-1 in the induction of the IL-1 beta and the TNF-alpha genes. AB - Bacterial LPS is a potent macrophage activator. The early steps in LPS signal transduction involve the tyrosine phosphorylation and activation of a number of kinases of the src family, and inhibition of this pathway causes a severe impairment in the production of the cytokines TNF-alpha and IL-1 beta. We find that LPS-induced macrophages activation also involves the Raf-1 kinase, a key component in mitogenic signal transduction. Treatment of BAC-1.2F5 macrophages with LPS causes phosphorylation and activation of Raf-1. This is paralleled by the stimulation of MEK-1 and MAP-kinase activity and by the phosphorylation of the transcription factor Elk-1, a nuclear target of MAP-kinase. Activation of the Raf/MAP-kinase pathway was inhibited upon pretreatment of the cells with genistein, a tyrosine kinase inhibitor. Raf-1 must thus lie downstream of tyrosine kinase in LPS signal transduction. However, Raf-1 is not a direct substrate of a LPS-induced tyrosine kinase, because Raf-1 immunoisolated from LPS induced cells contains only phosphoserine. This resembles the situation after CSF 1-stimulation of macrophages, in which Raf-1 clearly transduces a signal generated by the CSF-1 receptor kinase, but is phosphorylated exclusively in serine. Phosphopeptide maps of Raf-1 immunoprecipitated from LPS- or CSF-1 treated cells are indistinguishable, suggesting that these agents activate Raf-1 by similar mechanisms. Finally, v-raf-infected BAC-1.2F5 macrophages were found to constitutively express low levels of IL-1 beta and TNF-alpha. These data argue that Raf-1 functions downstream of tyrosine kinases in LPS-mediated macrophage activation and cytokine production. PMID- 7989772 TI - Captopril inhibits neutrophil synthesis of leukotriene B4 in vitro and in vivo. AB - The aim of this investigation was to determine the effects of metalloproteinase inhibitors on leukotriene (LT) A4 hydrolase in human neutrophil cytosol and to examine the effects of captopril on intact neutrophils in vitro and in vivo. Cytosolic fractions were assayed for LTA4 hydrolase and 5-lipoxygenase activity in the presence or absence of inhibitors. Only bestatin, 1,10-O-phenanthroline, captopril and fosinoprilat demonstrated significant effects. The IC50 of captopril and fosinoprilat for LTA4 hydrolase activity were 500 microM and 1 mM, respectively. No inhibition of 5-lipoxygenase activity in cytosolic fractions was detected. The effect of captopril was only minimally reversed by ZnSO4. The IC50 of captopril for inhibition of LTB4 synthesis in intact neutrophils was 63 microM. Furthermore, 5-HETE production in intact cells was diminished 25.3 +/- 8.5% in the presence of 1 mM captopril. Oral captopril inhibited stimulated LTB4 release by subsequently isolated neutrophils by 48.1 +/- 5.6% and 5-HETE release by 43.2 +/- 5.5%. Thus, captopril is an inhibitor of LTB4 synthesis in neutrophils in vitro and in vivo. However, there are differences between the potency of this drug as assessed in cytosol and intact cell studies. This study significantly extends previous reports in that it demonstrates that captopril is a more potent inhibitor of LTB4 synthesis in intact neutrophils than in cytosol and in that it demonstrates an inhibitory effect of captopril on synthesis of LTB4 by neutrophils exposed to captopril in vivo. PMID- 7989773 TI - LPS induces selective translocation of protein kinase C-beta in LPS-responsive mouse macrophages, but not in LPS-nonresponsive mouse macrophages. AB - Translocation of protein kinase C (PKC) after PMA or LPS stimulation has been studied in thioglycolate (TGC)-elicited murine peritoneal macrophages. Among the PKC subtypes we examined (alpha, beta, gamma, delta, and epsilon) by indirect immunostaining and immunoblot analysis, conventional PKC-beta, as well as novel PKC-delta and PKC-epsilon were found to exist in TGC-elicited C3H/HeN mouse macrophages. Translocation of PKC-beta to the Triton-stable cytoskeleton could be seen in macrophages after stimulation by both PMA and LPS. On the other hand, novel PKCs redistributed only after PMA stimulation. Macrophages obtained from LPS-nonresponsive C3H/HeJ mice also exhibited PKC-beta, and the m.w., cellular distribution, and cellular content of this enzyme could not be distinguished from those of C3H/HeN macrophages. These macrophages exhibited PKC-delta and PKC epsilon, as did the C3H/HeN macrophages. In these macrophages, however, LPS did not induce any remarkable change in the intracellular distribution of PKC-delta and PKC-epsilon or PKC-beta, whereas PMA was able to induce the translocation of PKC-beta to the cytoskeleton. These results suggest that LPS stimulation induces selective redistribution of PKC-beta in LPS-responsive macrophages, whereas a defect related to LPS unresponsiveness exists in C3H/HeJ mouse macrophages before the PKC activation. Translocation of PKC-beta can be understood to be an important event in LPS signaling in macrophages. PMID- 7989774 TI - Differential gene expression for IL-1 receptor antagonist, IL-1, and TNF receptors and IL-1 and TNF synthesis may explain IL-1-induced resistance to infection. AB - IL-1 pretreatment prolongs survival in lethal infection in normal and in neutropenic mice. We investigated whether this protection occurs by interference with deleterious cytokine effects. The effect of IL-1 pretreatment on concentrations of IL-1 alpha, IL-1 beta, IL-6, and TNF-alpha circulating in vivo and the ex vivo cytokine production capacity of macrophages was assessed in uninfected, non-neutropenic and neutropenic Swiss mice, in Swiss mice infected with Klebsiella pneumoniae (non-neutropenic mice) or Pseudomonas aeruginosa (neutropenic mice), and in neutropenic C3H/HeN and C3H/HeJ mice infected with P. aeruginosa. In Swiss and C3H/HeN mice, IL-1 pretreatment enhanced survival and reduced circulating TNF-alpha and IL-6 as well as LPS-stimulated production of IL 1 alpha and TNF-alpha. In C3H/HeJ mice, a lack of IL-1-induced protection was associated with low cytokine concentrations and production. In contrast, up regulation of mRNA for the IL-1 receptor antagonist (IL-1Ra) was observed in several organs of IL-1-pretreated mice, suggesting that IL-1Ra could attenuate deleterious IL-1 effects. In addition, IL-1 pretreatment down-regulated steady state mRNA for the type I IL-1R and the type I TNFR in several organs at the time of infection, suggesting desensitization of target cells as an additional mechanism of IL-1-induced protection. We conclude that the IL-1-induced protection is at least partially mediated by down-regulating cytokine production, and that the induction of IL-1Ra and the desensitization of target cells by receptor down-modulation may also contribute to this phenomenon. PMID- 7989775 TI - Macrophage function in simian AIDS. Killing defects in vivo are independent of macrophage infection, associated with alterations in Th phenotype, and reversible with IFN-gamma. AB - Infection of macrophages (M phi) in vitro with M phi-tropic isolates of simian immunodeficiency virus (SIV) did not affect killing of Cryptococcus neoformans up to 16 days after inoculation (p < 0.05). Conversely, alveolar M phi from animals with SIV-induced AIDS killed C. neoformans less efficiently (10.4 +/- 2.8% killing) and, when stimulated with phorbol myristate, produced less superoxide anion (O2-; 0.15 +/- 0.02 O2-/h/mg M phi protein) than M phi from uninfected monkeys (21.8 +/- 1.6% killing and 0.29 +/- 0.02 O2-/h/mg M phi protein). In contrast, killing and O2- release were accentuated in SIV+ asymptomatic animals (25.8 +/- 2.3% killing and 0.40 +/- 0.04 O2-/h/mg M phi protein; p < 0.05). M phi mediated killing and O2- production could be restored by culturing the affected cells in supernatants derived from Con A-stimulated PBMC of uninfected or SIV+ asymptomatic monkeys. Supernatants with restorative properties had high IFN-gamma bioactivity (63.4 +/- 11.0 U/ml) and elevated IL-10 concentrations (75.3 +/- 10.4 pg/ml) as compared with PBMC supernatants derived from animals with AIDS (IFN gamma, 9.7 +/- 4.9 U/ml; IL-10, 24.0 +/- 10.1 pg/ml). Functional restoration was found to be dependent, in part, on the presence of IFN-gamma, as neutralizing Abs to IFN-gamma significantly inhibited functional restoration in active supernatants. Moreover, the inactivity of supernatants from mitogen-stimulated PBMC cultures derived from animals with AIDS was not solely dependent upon the loss of CD4+ lymphocytes, inasmuch as purified pulmonary alveolar and peripheral blood CD4+ T cells from only uninfected and SIV+ asymptomatic animals, and not those from animals with AIDS, produced IFN-gamma upon mitogen stimulation. Collectively, these findings suggest that functional aberrations in alveolar M phi from animals with AIDS are not directly due to virus infection but likely result from changes in the pulmonary microenvironment in association with the multisystemic loss and dysfunction of CD4+ T cells. PMID- 7989776 TI - Elevated levels of shed type II IL-1 receptor in sepsis. Potential role for type II receptor in regulation of IL-1 responses. AB - Two types of cellular IL-1Rs have been characterized and cloned from both human and murine sources. The type II IL-1R has a very short cytoplasmic domain and does not seem to participate in IL-1 signaling. We demonstrate that type II IL 1Rs are released from the surface of neutrophils in response to treatment with TNF or endotoxin. In addition, serum from patients with sepsis syndrome contains elevated levels of soluble type II IL-1Rs. Neutrophils isolated from patients with sepsis have greatly enhanced expression of type II IL-1R mRNA and cell surface receptors and are therefore a likely source for the shed receptors in serum. Of the three forms of IL-1, soluble type II IL-1R binds IL-1 beta with highest affinity and also selectively inhibits IL-1 beta activity. We propose that increased cell surface expression and rapid release of preformed type II IL 1R from neutrophils, as a soluble IL-1 beta binding protein, represents a mechanism that has evolved for regulating IL-1 activity in sepsis. PMID- 7989777 TI - Induction of T cell tolerance by pretreatment with anti-ICAM-1 and anti lymphocyte function-associated antigen-1 antibodies prevents antigen-induced eosinophil recruitment into the mouse airways. AB - To determine whether the induction of Th2 cell tolerance down-regulates Ag induced eosinophil recruitment into the tissue, we studied the effect of the in vivo pretreatment with anti-ICAM-1 mAb, anti-LFA-1 mAb, and a soluble Ag on Ag induced eosinophil infiltration in the trachea of sensitized mice. The in vivo pretreatment with anti-ICAM-1 mAb, anti-LFA-1 mAb, and a soluble Ag inhibited Ag induced eosinophil infiltration in the mouse trachea in an Ag-specific manner. The pretreatment with anti-LFA-1 mAb and the Ag also had a weak inhibitory effect on the Ag-induced eosinophil infiltration. In contrast, the pretreatment with Ag alone, the combination of anti-ICAM-1 mAb and anti-LFA-1 mAb alone, or the combination of anti-ICAM-1 mAb and the Ag had no significant effect. In addition, the pretreatment with the two mAb and the Ag and, to a lesser degree, the pretreatment with anti-LFA-1 mAb and the Ag also prevented Ag-specific IgE production in mice. In vitro Ag-induced IL-2, IL-4, and IL-5 production was decreased in spleen cells of the mice pretreated with anti-ICAM-1 mAb, anti-LFA-1 mAb, and the Ag, but not with Ag alone or with the combination of anti-ICAM-1 mAb and anti-LFA-1 mAb alone, indicating the induction of both Th1 and Th2 cell tolerance in vivo. These results indicate that the induction of Th2 cell tolerance prevents Ag-induced eosinophil recruitment into the tissue and IgE Ab production and that ICAM-1/LFA-1 interaction is involved as a costimulatory signal in inducing T cell tolerance to a soluble Ag. PMID- 7989778 TI - The carboxyl-terminal region of HIV-1 Nef protein is a cell surface domain that can interact with CD4+ T cells. AB - Our previous studies have shown that the HIV-1 Nef Ag is expressed, at least in part, on the surface of infected cells. We demonstrated this by using membrane immunofluorescence and flow cytometry with Nef murine mAbs. To identify the domain of Nef exposed on the cell surface, epitope mapping of these and a new mAb was performed by ELISAs by using several recombinant truncated Nef fusion proteins and synthetic peptides. The results showed that mAbs F1, E7, E9, and 4H4 recognized Nef epitopes located at amino acid residues 148-157, 192-206, 158-206, and 1-33, respectively. The intensity of cell surface Nef staining was stronger with mAbs E7 and E9 than with F1, and there was no staining by 4H4, which indicates that the carboxyl-terminal region of Nef is predominantly exposed on the surface of HIV-1-infected T cell lines and PBMC. This surface Nef domain displayed high affinity for the surface of uninfected CD4+ T cells, because the binding of a soluble form of recombinant Nef protein to the cell surface was specifically blocked by the E7 and E9 mAbs or by synthetic peptides that contained the carboxyl-terminal region of Nef. In addition, syncytium formation between infected and uninfected cells also was specifically reduced by the same mAbs or peptides. Thus, the cell surface domain of Nef seems to play an important role in the interaction between HIV-1-infected and CD4+ uninfected T cells. PMID- 7989779 TI - Association of autoantibodies to topoisomerase I and the phosphorylated (IIO) form of RNA polymerase II in Japanese scleroderma patients. AB - Autoantibodies to RNA polymerases (RNAP) I and III are highly specific for scleroderma (SSc), whereas autoantibodies to RNAP II are associated with systemic lupus erythematosus (SLE) and overlap syndromes, as well as SSc. The specificities of autoantibodies to RNAP I, II, and III in 129 SSc sera were investigated in the present study. Immunoprecipitation and pulse-chase analysis demonstrated several patterns of autoantibody recognition of RNAPs. Some sera immunoprecipitated RNAP II only after its largest subunit was phosphorylated, suggesting that they contained autoantibodies that recognized an epitope carrying a phosphoamino acid. Autoantibody recognition of all three classes of RNAPs was influenced strongly by race. Although in SLE, autoantibodies to the phosphorylated form of RNAP II (RNAP IIO) were identified in all races, in SSc, these autoantibodies were seen in 21% of Japanese and 5% of Black patients, but never in Caucasians. A striking association of anti-RNAP IIO with anti topoisomerase I (topo I) autoantibodies was found in Japanese and Black SSc, but not SLE, patients. However, anti-topo I Abs were not associated with anti-RNAP IIO in Caucasians. Japanese SSc patients who were positive for both anti-RNAP IIO and anti-topo I Abs had a significantly higher frequency of diffuse disease, pigmentation changes, flexion contractures, and acro-osteolysis than patients having autoantibodies to topo I alone, and were diagnosed at a younger age (p < 0.05). These data suggest that genetic factors (possibly HLA-linked) influence autoantibody specificity, and that different autoantibody fine specificities may either cause, or be predictive of, different clinical outcomes. PMID- 7989780 TI - The repertoire of cytotoxic T lymphocytes in the recognition of mutant simian immunodeficiency virus variants. AB - The importance of the repertoire of a primed, AIDS virus-specific population of CTL in the recognition of emerging mutant viruses was assessed in simian immunodeficiency virus (SIV)-infected rhesus monkeys. These studies were done by using the well-characterized CTL recognition of the SIVmac Gag peptide 11C (p11C) epitope in rhesus monkeys expressing the MHC class I molecule Mamu-A*01. Lysis of peptide-pulsed targets by bulk PBL effector cells from SIVmac-infected, Mamu A*01+ monkeys was significantly decreased by mutations at residues 2, 3, and 5 of the nine-amino-acid Gag p11C epitope. However, effector cell lysis of targets pulsed with p11C containing substitutions at residues 3 or 5 was substantially increased by in vitro incubation of the monkeys' PBL with these mutant peptides. This suggested that expandable populations of cells exist in the primed CTL of infected monkeys capable of recognizing mutant peptide sequences. In fact, without in vitro exposure of PBL to mutant peptides, SIVmac Gag-specific CTL could be cloned from PBL of infected monkeys that lysed targets pulsed with mutant peptides. These observations suggest that clones of effector cells capable of recognizing many viral mutants may be able to expand in vivo to control the spread of emerging variant AIDS viruses. PMID- 7989781 TI - Peripheral expansion of human V gamma 9/V delta 2 T cells. PMID- 7989782 TI - [A technique of successfully performing an annuloplasty for narrowed aortic valvular annulus in aortic valve replacement]. AB - We previously reported that a significant reduction in both myocardial weight and left ventricular end-diastolic volume weight and left ventricular end-diastolic volume was achieved with the use of an artificial valve of 21 mm size in aortic valve replacement (AVR) performed on aortic stenosis patients with a body surface area of less than 1.4 m2. In those patients with a narrower valvular annulus on a unit body surface area basis, however, we have aggressively performed an operation of enlarging the valvular annulus in conjunction with AVR with a similar satisfactory hemodynamic improvement invariably in all cases, including 3 without autologous blood transfusion. In this paper mention is made, based on our experiences gained so far, of some points of critical technical importance for the successful performance of AVR involving annuloplasty, specification by the Manouguian's and Konno's procedure. PMID- 7989783 TI - [Postoperative pulmonary complications in patients undergoing thoracic surgery with special reference to preoperative respiratory muscle strength and nutrition]. AB - Postoperative pulmonary complications in patients undergoing thoracic surgery were examined along with their preoperative respiratory muscle strength and nutrition. Respiratory muscle strength was assessed by maximum inspiratory (MIP) and expiratory (MEP) pressures. Nutrition was assessed by serum levels of albumin and total cholesterol. The examined cases include 51 cases of lung tumors, 8 cases of mediastinal tumors, 9 cases of empyema, 3 cases of esophageal cancer, 2 cases of chest wall tumors, and 2 cases of giant bulla. Preoperative respiratory muscle training increased both MIP and MEP significantly (p < 0.01). Thirteen patients who had postoperative pulmonary complications had significantly lower values (p < 0.01), and did not show significant increases in either MIP or MEP even after training. The cases which experienced complications also showed significantly lower preoperative serum levels of albumin and total cholesterol (p < 0.01). Therefore, patients with respiratory muscle weakness and poor nutrition have a higher risk of postoperative pulmonary complications. PMID- 7989785 TI - [Relation between surgical outcome and preoperative end-systolic volume of the left ventricle in patients with regurgitant valvular heart disease]. AB - The relation between the end-systolic volume index of the left ventricle (ESVI (ml/m2)) and the early and late results after valve replacement were reviewed in 249 patients with pure aortic regurgitation (AR) and 189 patients with pure mitral regurgitation (MR). The patients with AR were classified into 4 groups (A1 A4) and those with MR were classified into 3 groups (M1-M3) according to the ESVI. The ESVI, the number of patients (No of P), early mortality rate (EM) and the actuarial survival rate at 12 years after valve replacement (AS at 12 yr) in each group are shown in the following Table. [table: see text] The actuarial survival rate at 12 years after operation in A1 and A2 were significantly lower than that in A3 and A4. In 57% of the late deaths in A1 and A2 patients, the cause of the death was thought to be rhythm disturbance. In contrast, there were no differences in late survival among the three groups with MR (M1, M2 and M3). The minor axis of the left ventricle at end-diastole and at end-systole (Dd and Ds) and shortening fraction of the left minor axis (FS), evaluated by echocardiography, were normalized early after the operation in A1 patients only. The Dd, Ds and FS in A2 and A3 returned to normal late after the operation. However, in A4, these parameters still remained abnormal. Thus, patients with a deteriorated left ventricle can survive the operation. However, the long-term results in patients with AR with ESVI more than 150 ml/m2 were unsatisfactory.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7989784 TI - [Surgery of type A acute aortic dissection with gelatin-resorcin-formal (GRF) biological glue--study of six cases]. AB - GFR (Gelatin-Resorcin-Formalin) glue consists of mixture of gelatin and resorcin. The mixture is hardened by the addition of medical form-aldehyde, creating tridimensional network. From August 1991 to February 1993, six patients of type A acute aortic dissection underwent repair of false lumen with GRF glue. Including one female, the mean age was 57.3 years old ranged 51 years old to 64 years old. The entry of aortic intima were found in the ascending aorta in 4 cases, in the greater curvature of aortic arch in one case, and in the lesser curvature of aortic arch in one case. We used GRF glue for adhesion of intimal and medial wall of dissecting aneurysm in all cases. In case 1, the ascending aorta was replaced with a ringed intraluminal graft, and in case 2, the ascending aorta was replaced with a graft. In case 3 and 4, the aortic wall was closed primarily using GRF glue after patch closure of an entry. In case 5 and 6, the ascending aorta including an aortic arch was replaced with a graft. We revealed that GRF glue could harden the thin wall of aorta in the acute phase. PMID- 7989786 TI - [Left ventricular characteristics after Jatene operation for transposition of the great arteries with intact ventricular septum--comparative study of neonatal primary and two stage repairs]. AB - Left ventricular characteristics in late postoperative period after the arterial switch operation (ASO) was evaluated in fifty-nine patients with transposition of the great arteries and intact ventricular septum. They included 22 neonates who underwent a neonatal ASO (Group I) and 37 patients who underwent a two-stage ASO (Group II). Group II was subdivided into two groups according to the presence or absence of aortic regurgitation in the late postoperative period as group IIa (aortic regurgitation [-], 22 patients) and group IIb (aortic regurgitation [+], 15 patients). Age at ASO ranged from 4 to 27 days (average 12.7 days) in the group I, 5 to 43 months (average 12.7 months) in the group IIa, and 4 to 54 months (average 16.3 months) in the group IIb. Postoperative follow-up period ranged from 8 to 68 months (average 25.0 months) in the group I, 12 to 74 months (average 59.0 months) in the group IIa, and 19 to 66 months (average 48.5 months) in the group IIb. Left ventricular end-diastolic volume was significantly smaller in the group I (123 +/- 19% of normal) than the group IIa (146 +/- 38 of normal) and the group IIa (183 +/- 53% of normal). And left ventricular ejection fraction was significantly higher in the group I (67 +/- 5%) than the group IIa (62 +/- 11%) and the group IIb (58 +/- 8%). Left ventricular normalized mass was significantly smaller in the group I (85 +/- 11% of normal) than the group IIa (113 +/- 14% of normal) and the group IIb (130 +/- 9% of normal).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7989787 TI - [Investigations of the use of IABP during open heart surgery]. AB - Since 1977, IABP has been employed in 180 cases. We studied 94 adult patients who underwent open heart surgery and were treated with IABP procedure for the past 10 years, and investigated the following items, the timing of IABP initiation, preoperative left heart functions, aortic clamping time, period of IABP use, and mortality. Additional, P-V loop was measured during the operation. The following conclusions were drawn. When IABP was used preoperatively in cases with deteriorated cardiac functions, the incidence of in cases in which IABP was used during or after the operation. P-V loop is useful to obtain the detail of cardiac function which provides sufficient patient management during and after the operation, and could be useful for establishing the criteria of IABP use. PMID- 7989788 TI - [Results and operative indications of lobectomy with bronchoplasty for bronchogenic carcinoma]. AB - We evaluated the results and operative indications of bronchoplastic lobectomy in patients with bronchogenic carcinoma. From 1980 to 1992, 34 patients underwent lobectomy in combination with bronchoplastic procedure for lung cancer. In regard to histological typing, they consisted of 18 squamous cell carcinoma, 9 adenocarcinomas, 3 large-cell carcinomas, 2 combined types of adenocarcinoma and squamous cell carcinoma, 1 small-cell carcinoma, and 1 carcinosarcoma. Five-year survival rate of 18 cases of squamous cell carcinoma was 41.2%, whereas 9 cases of adenocarcinoma died within 3 years. We classified 34 cases into two groups according to the reason of indication for bronchoplasty. Group T (n = 19) was the case whose tumor was spreading to the major bronchus. Group LN (n = 14) was the case whose metastatic lymph nodes were invading to the major bronchus. Forty-two percent of Group T was stage III or IV, while 93% of Group LN was stage III or IV. Five-year survival rate was 54.7% in Group T, and 8.1% in Group LN. There were statistical differences between both groups (p < 0.05). In 73 patients who underwent pneumonectomy at the same period, 5-year survival rate was 31.7%. In conclusion, the bronchoplastic procedure is recommended to Group T in comparison with that of Group LN. PMID- 7989789 TI - [Experimental study of optimal perfusion pressure during retrograde cerebral perfusion]. AB - The effects of retrograde perfusion pressure on the brain was experimentally investigated during profound hypothermic circulatory arrest. Fifteen adult mongrel dogs were placed cardiopulmonary bypass and induced profound hypothermia of 20 degrees C at nasopharyngeal temperature. Retrograde cerebral perfusion (RCP) with perfusion pressure of 10 mmHg (RCP10; n = 5), 20 mmHg (RCP20; n = 5), 30 mmHg (RCP30; n = 5) underwent for 60 minutes. The oxygenated blood was infused via the bilateral maxillary veins, and the flow rate was kept to maintain a desired pressure in the external jugular vein for each group. Regional cerebral blood flow (rCBF), excess lactate, cerebrospinal fluid pressure (CSFP), adenosine triphosphate (ATP) concentration of cerebral tissue, and water content of cerebral tissue were measured. In the RCP10 group, cerebral excess lactate was positive and ATP concentration was low. In the RCP30 group, the water content of cerebral tissue was significantly higher than those in the other groups. In the RCP20 group, the excess lactate was maintained in a negative range, and ATP concentration was significantly higher than in the RCP10 group. In conclusion, RCP may provide metabolically adequate support for the brain and a perfusion pressure of 20 mmHg was appropriate for RCP in dogs. PMID- 7989790 TI - [Morphological comparison between arterial grafts and venous grafts]. AB - We have extendedly used arterial grafts in coronary bypass surgery because of their better patency rate. We have operated 134 cases of coronary bypass during recent 27 months. Postoperative angiography showed high patency rate in arterial grafts, such as 97% (59/61) of right internal thoracic artery (RITA), 98% (107/109) of left internal thoracic artery (LITA), 96% (83/86) of right gastroepiploic artery (RGEA), comparing with 86% (26/30) of saphenous vein graft (SVG). Pathological examination was done by specimens of grafts obtained during operation. Vasa vasorum was poorly developed in ITA and RGEA. ITA had several layers of elastic fiber in media and RGEA had smooth muscular media. Both arterial grafts showed low atherosclerotic scores (intima/media), 7.1% in RITA, 7.3% in LITA and 6.8% in RGEA. But some cases with hyperlipidemia and/or diabetes showed high score of atherosclerosis in arterial grafts. Endothelial cells were well preserved in both arterial grafts after harvesting, in contrast with poor endothelial preservation in SVG. Endothelial appearance of RGEA was similar to that of the coronary artery and different from that of ITA. RGEA is superior grafts for CABG as coronary bypass because of their structural superiority. PMID- 7989792 TI - [Coronary intervention in patients less than 40 years of age]. AB - Forty-eight patients less than 40 years of age who underwent coronary intervention (coronary artery bypass grafting, CABG or percutaneous transluminal coronary angioplasty, PTCA) were identified and compared with a control group (patients more than 40 years of age who underwent coronary intervention). In addition, the treatment of hyperlipidemia after coronary intervention was studied in patients who required re-intervention and in those who were event free. There were no early nor late deaths and good early results were obtained in young patients, but late follow-up demonstrated that a re-intervention rate in young CABG patients was significantly higher than that in patients aged over 40 years (23.3% vs 9.3%), while in PTCA patients it was also higher in younger patients than in older patients (5.6% vs 1.3%). However, early results in PTCA patients showed the restenosis rate in young patients was significantly lower than that in older patients (7.7% vs 40.7%). Event free curve showed that earlier re intervention was necessary for PTCA patients than for CABG patients. Hyperlipidemia was not well controlled by treatment in either group. The use of arterial grafts will improve the late results of younger patients. The patency of grafts and the quality of life of young patients should be the focus of future investigation. PMID- 7989791 TI - [Effect of left heart bypass on right ventricular function in normal and acute heart failure dogs--an application of the conductance catheter to the right ventricle]. AB - We investigated right ventricular function during left heart bypass (LHB) with 18 mongrel open-chest dogs, in normal and acute heart failure (AHF) dogs which underwent aortic cross clamp. Left ventricular unloading was completely accomplished with a centrifugal pump. For more accurate evaluation of right ventricular volume, conductance catheter was employed to assess right ventricular function. Analysis were performed with right ventricular pressure-volume curve which was changed by transient volume loading on right ventricle. And right ventricular properties with and without LHB were compared by the use of load independent parameters as follows. Right ventricular systolic property was evaluated by maximum elastance (Emax) and stroke work-end-diastolic volume relation (SW/EDVR), and its diastolic function was evaluated by end-diastolic pressure-volume relation (EDP/VR). Overall right ventricular performance was assessed by stroke work-end-diastolic pressure relationship (SW/EDPR). In the normal heart, only a parallel shift to the right in EDP/VR and SW/EDVR was noted without any significant changes in slope with LHB. On the other hand, in AHF dogs, the slope of SW/EDVR and SW/EDPR were increased from 0.14 +/- 0.08 to 0.18 +/- 0.08 (p < 0.05), from 0.22 +/- 0.15 to 0.34 +/- 0.19 (p < 0.01), respectively, and the curve of EDP/VR was shifted right and downward. These result suggested that decompression of the left ventricle and septal shifting by LHB provided good diastolic compliance and afterload unloading of the right ventricle, and these effects had a more significant role in acute heart failure than in the normal heart. PMID- 7989793 TI - [Autologous pulmonary arterial flap for repair of truncus arteriosus in neonate and small infants]. AB - Complete correction without external conduit repair by autologous pulmonary arterial flap was performed for the truncus arteriosus in one neonate and two small infants. In this study, we investigated advantages of postoperative hemodynamics and pulmonary artery growth from the data on truncus arteriosus repaired by the autologous flap technique. Patient in this study was classified as type I or II truncus arteriosus and age ranged from 19 days to 95 days after birth. One of the patients died of unexpected gastric bleeding 25 days after surgery. However, all showed excellent hemodynamics in the early postoperative period. The reconstructed pulmonary tract positioned rather left ward and posterior to the level of the systemic root than the technique with extra cardiac conduit repair. Compression did not occur at the created pulmonary tract and hemodynamics was fairly stable after closure of the chest. The postoperative RVP/LVP ratio ranged among 0.45 to 0.65 and the pressure gradient across the right ventricular out flow tract demonstrated only 10-15 mmHg. The size of the pulmonary arterial flap was sufficient even in type II truncus arteriosus to create right ventricle-to-pulmonary tract. However, the first patient underwent subsequent surgery 20 months after the initial surgery, because of left pulmonary artery stenosis due to intimal tissue overgrowth distal to the outflow patch. Surgical findings revealed that the posterior wall of the pulmonary tract was smooth and well developed. Traction of pulmonary arterial flap toward the right ventricular outflow tract shortens the distance between monocusp and left pulmonary arterial orifice than expected.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7989795 TI - [Modified Naclerio-Langer method under thoracoscopic procedure for pneumothorax due to rupture of a large bulla]. AB - We managed a patient with pneumothorax caused by a large bulla by so called modified Naclerio-Langer method under thoracoscopic procedure. A 76-year-old female was hospitalized with recurrent left pneumothorax. Uncer the right lateral position, 3 Surgi ports were inserted through 5, 7, 9th intercostal space. There was a large bulla, 10 cm in diameter, with rupture at the ventral side. The bulla wall was partially resected and many bronchiolar openings were seen at the caudal side. Gregarious bronchiolar openings were resected with Endo GIA. Two residual openings were closed with 3-0 Dexon suture. The base of bulla was pleuralised by suturing the edges of the removed cyst with running suture of 3-0 Dexon. Because no air leaks was detected, a chest drain was inserted. Operation time was 215 minutes and she was discharged on 20th postoperative day. This procedure is usefull and not invasive. PMID- 7989794 TI - [Replacement of the prosthetic aortic valve within a composite graft]. AB - In 1974, a 36-year-old man underwent composite graft replacement of the aortic valve and the ascending aorta with a Starr-Edwards prosthesis (2320). In 1993, he had hemolytic anemia due to cloth wear of the Starr-Edwards prosthesis. The prosthetic aortic valve was removed and replaced without replacement of the conduit. This technique was simple and safe, and was useful to avoid unnecessary dissection. PMID- 7989796 TI - [A case of aortic and mitral regurgitation with two aneurysms in the mitral valve]. AB - A 59-year-old male was found to have two aneurysms in the mitral valve, mitral regurgitation, and aortic regurgitation by the echocardiographic examination. The patient had a previous history of infectious endocarditis by streptococcus at the age of 24. Under the diagnosis of mitral aneurysms developed after infectious endocarditis, surgery was undertaken. A 5 x 8 mm sized perforation in the right coronary cusp and two aneurysms in the anterior mitral leaflet, 22 mm and 17 mm in size, were found intraoperatively. Both the mitral and aortic valves were replaced. Patients with a history of infectious endocarditis have to be followed up for a long period of time. Transesophageal echocardiogram is useful in those patients. Considering high prevalence of aortic valvular diseases in those with a mitral aneurysm after infectious endocarditis, aortic valves should be carefully evaluated. PMID- 7989797 TI - [A case of operation for acute postinfarction mitral insufficiency due to papillary muscle rupture]. AB - A 75-year-old man was brought to hospital with complaining of chest pain. He was diagnosed acute myocardial infarction and treated medically using thrombolytic drugs. Without chest pain relieved, cardiac catheterization revealed three coronary vessel disease and severe mitral insufficiency (MR). MR was diagnosed due to papillary muscle rupture by echocardiography. After being transferred to our hospital, the patient developed in shock and underwent emergency operation with IABP inserted. Triple CABGs (to LAD, PD and 4PL) and mitral valve replacement were performed using saphenous vein grafts and a mechanical valve (Carbomedicus 25 M). The patient recovered gradually and discharged one and a half month after operation. PMID- 7989798 TI - [Surgically successful treatment of pleural empyema with multiple bronchial fistulae--a case report]. AB - A 62-year-old man who had undergone left lingual segmentectomy for pulmonary tuberculosis developed left chronic localized pleural empyema with multiple bronchial fistulae in the region of surgical gauze left in the thoracic cavity. We surgically removed the gauze and fenestrated the empyema. After disinfection of the region of suppuration, small fistulae which were less than 2 mm in diameter were closed by fibrin-glue-packing and consolidation of the orifices using 40% silver nitrate solution. Two and one-half months later a second operation was performed. Residual large fistulae were closed by fibrin-glue packing and suturing of their orifices, and the empyema space was then obliterated by muscle flap plombage. The patient's postoperative course was good and the empyema was completely cured with this treatment. PMID- 7989799 TI - [A case report of the maze procedure with mitral valve replacement]. AB - The maze procedure was performed simultaneously with mitral valve replacement for atrial fibrillation and mitral stenosis in a 66-year-old female. On the first postoperative day, the cardiac status deteriorated suddenly due to a very rapid heartbeat which was later diagnosed as a 1:1 AV conduction of atrial flutter. The atrial flutter responded to an injection of verapamil and changed to a 2:1 conduction. Although atrial flutter had continued until the thirteenth postoperative day, the heart achieved sinus rhythm on that day. Since then it has continued without any antiarrhythmic drugs except digitalis. It was difficult to make a diagnosis of the rapid heartbeat on the 12-lead ECG because P waves could not be seen clearly on the ECG. Recording the electrical cardiac status by using the temporal atrial pacing leads, which were placed during the operation, was helpful in diagnosing the heartbeat as atrial flutter. The electrophysiological examination eight weeks after the operation revealed that the sinus node function was normal and atrial flutter or atrial fibrillation could not be induced. The patient is well and in sinus rhythm 12 months after the operation. PMID- 7989800 TI - [A case of squamous cell carcinoma of negative tumor shadow arising from pulmonary cyst]. AB - We report a case of 53-year-old man who performed resection of infected cystic lung lesion seen from his childhood. Chest X-ray showed no remarkable change in the wall of the cyst, and tumor shadow was negative. As the chest cavity was severely adhesive, operation was ended in partial resection including the cyst. Pathological study revealed moderately differentiated squamous cell carcinoma replacing the entire cystic wall. Right upper lobectomy and dissection of lymph nodes were performed as second operation. Microscopically, carcinoma was limited in the wall of the cyst. PMID- 7989801 TI - [Adverse effect of internal thoracic artery steal on perioperative hemodynamic condition--a report of three cases]. AB - In three patients who had suffered from perioperative hemodynamic deterioration after myocardial revascularization with an internal thoracic artery to the left anterior descending coronary artery (LAD), blood steal from the ITA into large side branches was strongly suspected. In two of them an intractable ventricular fibrillation occurred before closure of the chest. Additional insertion of saphenous vein graft to the LAD enabled them to get out of jeopardy. Postoperative angiographic studies demonstrated large pericardial branches which had several fistulous communications with the pulmonary circulation. The other suffered from anteroseptal myocardial infarction immediately after an uneventful operation. Postoperative angiography revealed an enlarged lateral costal branch which gave off four intercostal arteries. Careful and meticulous harvesting of the ITA is mandatory to avoid tragic consequences caused by its large side branches. PMID- 7989802 TI - [Tetralogy of Fallot with a restrictive ventricular septal defect caused by a membranous flap]. AB - A 5-year-old boy who had typical tetralogy of Fallot (TOF) with mild cyanosis was referred to us. Preoperative echocardiogram revealed that in addition to the TOF morphology, an abnormal piece of tissue attached to the right side of the ventricular septum was floating and obstructing flow through the ventricular septal defect (VSD) in systole. Preoperative cardiac catheterization showed suprasystemic right ventricular pressure with a gradient of 60 mmHg between the right ventricle and the aorta, and a right ventriculogram demonstrated a narrow radiolucent structure beneath the aortic valve in the right ventricle. During surgery a fibrous membranous tissue, with no relation to the tricuspid valve, was found to extend from the edge of the VSD to the aortic valve and to partially occlude the defect. This tissue was used as a suture anchorage for patch closure of the defect. Preoperative echocardiography is useful to detect such flaps and early surgical correction should be done to prevent right ventricular failure resulting from right ventricular pressure overload. PMID- 7989803 TI - [Aortic dissection with giant pseudoaneurysm as a rare late complication of aortic valve replacement--a case report]. AB - A 60-year-old man who had received aortic valve replacement for aortic regurgitation at 47 years of age developed sudden syncope and shock on Mar. 28, 1991. Close examination including CT scan and aortography revealed DeBakey type I aortic dissection with giant pseudoaneurysm which compressed superior vena cava and right pulmonary artery and caused superior vena cava syndrome. He underwent elective ascending aortic replacement under profound hypothermic cardiopulmonary bypass and circulatory arrest on Jun. 17, 1991. The giant pseudoaneurysm was present posterolaterally to the ascending aorta. It communicated with the false lumen and contained massive thrombi. The intimal tear of the ascending aorta existed along the suture line of previous aortotomy. PMID- 7989804 TI - [Combined coronary artery bypass grafting and choledocholithotomy--a report of two cases]. AB - A 74-year-old man and a 66-year-old woman were diagnosed as angina pectoris with choledocholithiasis. Combined coronary artery bypass grafting and choledocholithotomy were performed successfully in the two cases. For the prevention of cardiac complications and mediastinal infection, coronary artery bypass grafting was performed prior to choledocholithotomy. However, skin incisions were different in both cases. In the case with the biliary tract infection, both two surgical procedure were performed through a single skin incision in order to prepare the gastroepiploic artery as a graft. The combined operation is considered to be useful in selected cases with ischemic heart disease and choledocholithiasis. PMID- 7989805 TI - [Traumatic transection of the descending thoracic aorta--2 successful case reports]. AB - We report two cases of acute traumatic transection of the descending thoracic aorta that were successfully treated. Case 1 (a 24-year-old male) was admitted to our hospital because of unconsciousness with multiple severe injuries including pelvic fracture, hepatic laceration, brain contusion, and multiple fractures in the extremities. An emergency operation was performed to control the active bleeding from the hepatic laceration and the transluminal arterial embolisation of the internal iliac arteries for the pelvic fractures. Since the condition of the patient was very serious, we had to wait the repairment of the thoracic aorta for 3 weeks. The operation was successful using extracorporeal circulation. Case 2 (a 22-year-old female) suffered traumatic transection of the descending thoracic aorta without other injuries and received an emergency operation, which was successful. The strategy for the treatment of an aortic transection is difficult, especially when involving multiple injuries. However provided the decision to operate takes careful account of the general condition of the patient, then a successful result might be obtained even in a very severe case. PMID- 7989806 TI - [A resected case of pulmonary plasma cell granuloma infiltrating the pericardium]. AB - The patient was a 66-year-old man. An abnormal mass on his chest X-ray was pointed out during a regular check-up in November 1991. He was admitted to our hospital with the chief complaint of productive cough in January 1992. With the diagnosis of lung cancer, right middle and lower lobectomy with lymph node resection and partial resection of the pericardium was carried out. The pathological examination revealed pulmonary plasma cell granuloma infiltrating the pericardium. Postoperative course was uneventful. No recurrence was seen 17 months after operation. As pulmonary plasma cell granuloma is histologically benign, this was a very rare case with extra-pulmonary extension. Up to present, only 8 cases including this case has been reported in the literature. We reviewed these 8 cases. PMID- 7989807 TI - [Insertion of prosthetic tricuspid valve two years after the tricuspid valvulectomy]. AB - A case of a 14-year-old boy who underwent a prosthetic tricuspid valve insertion two years after the tricuspid valvulectomy due to intractable right-sided active endocarditis is presented. At the initial operation, the tricuspid valve was thoroughly resected because of marked destruction and attachment of vegetations, and a concomitant ventricular septal defect was directly closed. When a prosthetic valve was placed in the tricuspid portion, a semicircular Dacron patch was attached to the right side of the interventricular septum in a fashion of up chord and down-arc to cover the bundle of His. The straight edge of the patch was located near the AV node and was not sutured to the tricuspid valve annulus. A 31 mm of CarboMedics prosthetic valve was sutured to the tricuspid valve annulus and to the free edge of the patch at the position near the AV node to prevent AV block. Postoperative course was uneventful and ECG showed regular sinus rhythm. PMID- 7989808 TI - [A case of chylomediastinum following open heart surgery via median sternotomy]. AB - The case was a 17-year-old woman on whom open heart surgery was performed for ASD. Anterior mediastinal drainage alone revealed chyloid liquid, leading to diagnosis as chylomediastium. Ramification of thoracic duct and direct injuries of thymus and lymphoduct were presumed to be responsible for the occurrence of this complication. Operative treatment was positively performed because of its unimprovement by conservative treatment. Re-operation led to its healing in a comparatively short period of time. Idea of disease, cause of occurrence, and plan of treatment of this complication were examined for reporting below. PMID- 7989809 TI - [Successful repair of acute traumatic rupture of the thoracic aorta]. AB - We report four male patients (from 18 to 36 years in age) with acute traumatic rupture of the aortic isthmus due to blunt chest trauma caused by motor vehicle accident in three patients and a full in one patient. Of these patients, 3 underwent segmental replacements of the descending thoracic aorta with vascular prosthesis using cardiopulmonary bypass, and an additional patient underwent the same procedure using left heart bypass. All patients survived without the development of any serious complications. Since traumatic rupture of the thoracic aorta due to blunt trauma frequently occurs in the relatively young, some form of assisted circulation is necessary to prevent the ischemic spinal cord injury from cross clamping of the aorta during repair of the rupture. We prefer cardiopulmonary bypass as a most appropriate support in emergency situations, because extensive mediastinal hematoma or sudden hemorrhage could make dissection extremely hazardous without it. However, cardiopulmonary bypass requires systemic heparinization, which predisposes the patients with associated multiple injuries to a tendency of bleeding. Thus, a thorough investigation of the preoperative status, including the severity of multiple injuries, should be undertaken, and appropriate therapeutic measures instituted before the start of cardiopulmonary bypass. The determination of the timing of operation is crucial to success in the treatment of acute traumatic ruptures of the thoracic aorta. PMID- 7989810 TI - [Retrograde continuous warm blood cardioplegia]. PMID- 7989811 TI - Is it possible to identify the psychologically "bad risk" orthognathic surgery patient preoperatively? AB - Everyone involved in orthognathic surgery would like some means of identifying the so-called psychologically "bad risk" patient. This article reviews a number of techniques and concludes that, not only is this identification impossible to achieve, but it is probably unnecessary since most patients do well psychologically after orthognathic surgery regardless of their preoperative psychological profile. The few psychologically dissatisfied patients cannot be accurately identified preoperatively. PMID- 7989812 TI - Skeletal and dental arch asymmetries in individuals with normal dental occlusions. AB - The aim of this study was to determine whether skeletal and/or dental asymmetries are presented in individuals with normal dental occlusions. Frontal cephalometric radiographs and dental arch casts were obtained from 20 Brazilians from Rio de Janeiro whose mean age was 22.4 years. Normal dental occlusions were present in all individuals. Nine bilateral triangles were established on the radiographs for the craniodentofacial complex. The area for each triangle was calculated, and the frequency of asymmetries on the dental casts was investigated. When comparing right and left sides on the radiographs, Student's tests did not show statistically significant differences in triangle areas, although the areas were not symmetrical. Males and females showed similar results when the areas of the radiographic triangles were compared between sexes. Maxillary and mandibular dental midlines, palatal raphe on the casts, and median sagittal plane on the radiographs were almost coincident. Additionally, the frequency of molar asymmetries on the dental casts was not statistically different, but molar asymmetries greater than 1 mm were present in 50% of the sample. PMID- 7989813 TI - Resorption patterns following intentional vital root transection in Macaca mulatta. AB - Previous studies have shown degeneration of nerve tissue as well as reorganization by periodontal tissue in dental pulp chambers following intentional vital root transection in Macaca mulatta. The supporting structures of the teeth, as well as the root itself, have not been fully studied following such surgery. The purpose of this study was to observe histopathologic changes in bone and root structure over a 1-year postoperative period. Three adult Macaca mulatta were evaluated for this study. Roots were transected within the apical one third and the areas were surgically closed. Following a postoperative soft diet for 7 days, the monkeys were allowed normal masticatory function. Maxillary and mandibular quadrants were removed following vascular perfusion of the animals at 1, 2, 3, 6, 24, and 52 weeks; quadrants were then demineralized, embedded, sectioned, and stained with Preece's trichrome. Resorption of cementum, dentin, and bone was independently evaluated on microslides for each tooth at consecutive intervals of approximately 70 microns. Resorption was rated as mild, moderate, or severe depending on the number of Howship's lacunae and the dimension of the resorptive area. Severe bone resorption was evident at 1 week, decreasing at 2 weeks, and then progressively decreasing up to 52 weeks. Most active inflammatory root resorption was noted on maxillary and mandibular premolars and molars on first-week specimens. Arrested resorptive areas were present in similar locations in second- and third-week specimens. New cementum was present along the cut surface on specimens from 2 to 52 weeks and within the pulp canal beginning at 2 weeks.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7989815 TI - Periodontal complications following orthognathic surgery and genioplasty in a 19 year-old: a case report. AB - Bimaxillary osteotomies and a sliding genioplasty were performed to correct mandibular micrognathia and maxillary vertical hyperplasia in a 19-year-old white male with a Class II, division 1 malocclusion and anterior open bite. At a follow up appointment with the orthodontist 4 weeks after the surgical procedure, the mandibular anterior teeth showed severe gingival recession, exposing labial root surfaces on the mandibular central incisors. Grafting procedures were able to restore labial soft tissue on the affected teeth. It is suggested that wound healing contraction of gingival tissue in the area of the incision for the genioplasty caused this complication. PMID- 7989814 TI - Prospective analysis of antibiotic prophylaxis for orthognathic surgery. AB - A randomized prospective study of 30 patients was undertaken to evaluate antibiotic prophylaxis for orthognathic surgery. Perioperative, high-dosage antibiotic administration was compared to an existing prophylactic regimen employing longer intervals and continued postoperative antibiotics for 7 to 10 days. No significant difference was found between the two groups with respect to incidence of infection. Other variables studied included gender and age of patients, type of surgery performed, procedure length, and use of fixation. PMID- 7989816 TI - The accuracy of computerized prediction of the soft tissue profile: a study of 25 patients treated by means of the Le Fort I osteotomy. AB - This study was performed to compare the soft tissue movements in facial profile predicted by a computer package with those that had actually occurred following a maxillary advancement osteotomy. The source of the material was serial lateral cephalograms for 25 consecutive patients who had received similar Le Fort I osteotomies primarily to correct an anteroposterior skeletal discrepancy. Many of the digitized points on the soft tissue profile were surprisingly well predicted by the computer package. The chin and profile changes resulting from mandibular autorotation and/or a genioplasty were generally predicted accurately. However, in some cases prediction was less consistent, particularly in the region of the nose and upper lip. In this latter group of patients, initial size, thickness, and morphology of the soft tissues appeared to be important factors to which some consideration could be given in the further refinement of this type of software. PMID- 7989817 TI - Helping patients with their decisions. PMID- 7989818 TI - Developing measures of patients' perceptions of orthognathic surgery. AB - Measurements of patients' perceptions of the benefits, costs, and risks of orthognathic treatment are needed to assess the utility of alternative treatments, and to assess and improve patient education to make informed decisions. A two-part study was conducted to develop and evaluate measures assessing patients' perceptions of the benefits and risks of orthognathic surgery in comparison to an orthodontics-only approach or no treatment. The first part of this study included 49 patients who had completed orthodontics and orthognathic surgery and 34 patients considering orthognathic surgery. All patients were asked to complete an open-ended telephone questionnaire about their perceptions of the benefits and risks of orthognathic surgery and of alternative options. Patients' answers were sorted into categories, and the second part of this study included a closed-form written questionnaire to assess the perceived likelihood of possible outcomes in each category. Reliability of the questionnaire was assessed using Cronbach's alpha coefficient of internal consistency reliability. Cronbach's alpha ranged from 0.74 to 0.91 when the instrument was used to assess either overall benefits or risks of orthognathic surgery, orthodontics only, or no treatment, indicating acceptable reliability for each of these uses. Subscales concerning more narrowly defined aspects of benefits and risks were less reliable than the overall scales. PMID- 7989819 TI - Determinants of facial attractiveness in a sample of white women. AB - Esthetic evaluation of a photographic profile slide of a random sample of 130 adult white women was made by six judges. The esthetic evaluation included vertical and anteroposterior evaluation and an attractiveness score on a visual analog scale. Additionally, the judges were asked to give specific reasons for their scores. Profiles with increased vertical features or convex or Class II tendency profiles were judged as being the most unattractive. Judgment of facial appearance was consistently related to certain regions of the face: the chin, upper lip, and nose having the greatest effect on the overall judgment of appearance. Orthodontic and surgical treatment planning should focus primarily on these regions to obtain the best esthetic result. PMID- 7989820 TI - Anomalies of the branchial apparatus: a case report and review of embryology, anatomy and development. AB - The majority of congenital anomalies occurring in the neck are related to the development of the branchial apparatus. This area is responsible for the development of multiple structures in the head and neck and thus its anatomy and embryology are complex. Although cysts, sinuses, and fistulas of the branchial region are not common occurrences, they do present in a variety of settings and are generally easily managed if diagnosed early. A fundamental understanding of their anatomy, embryology, and presentation is needed to appropriately diagnose and manage them. These fundamentals are reviewed and a case report is used to illustrate one of the more common presentations. PMID- 7989821 TI - Unusual presentation of a secondary malignancy with an unknown and a known primary malignancy. PMID- 7989822 TI - Kidney and pancreas transplantations in Kentucky: an option whose time has come! PMID- 7989823 TI - Medical gender politics. PMID- 7989824 TI - Medicare fraud alert. PMID- 7989825 TI - Too many tests and procedures? PMID- 7989826 TI - Toynbee Memorial Lecture 1994: mastoid surgery and the Hong Kong Flap. AB - Critical evaluation of the outcome of surgery for cholesteatoma has favoured open cavity techniques. These methods have however been plagued by an inability to consistently produce healthy well healed cavities. The strength and stability of the normal tympanic membrane depends upon the separation of squamous epithelium from the middle ear mucosa by a fibrous tissue layer. Traditional methods of dealing with the cavity fail to reproduce a similar anatomically stable arrangement. In order to achieve the highest percentage of dry, stable disease free ears after employing basic surgical principles of wide access to facilitate meticulous removal of all cholesteatoma, we have utilized a vascularized deep temporalis fascia flap for complete coverage of the cavity eliminating all raw areas. This fibrous layer provides the optimal substrate for epithelial resurfacing. Excellent healing even under unfavourable circumstances is ensured by the rich blood supply to the pedicled temporalis fascia flap. Considering patient preferences and cost effectiveness, the optimal treatment for cholesteatoma must be one operation, provided it achieves a dry safe ear. Based upon rational concepts, the 'Hong Kong Flap' technique of reconstructing the mastoid cavity involves a straightforward procedure requiring no special technical skill that consistently achieves this ideal. PMID- 7989827 TI - Clinical applications of transcranial bone conduction attenuation in children. AB - It is a common belief that there is no significant transcranial attenuation across the skull by bone conduction (BC). In 32 children with proven unilateral sensorineural hearing loss the unmasked bone thresholds were measured on each side. There was a significant attenuation of BC at 4 kHz. Transcranial attenuation of BC at 4 kHz may explain the difference in sound perception between the two ears when bone conduction amplification is used. Further research should be undertaken to identify the better cochlea in mixed hearing losses. PMID- 7989829 TI - Maxillary sinusitis in children with otitis media with effusion. AB - Sinus radiographs have been carried out on 240 new cases of childhood otitis media with effusion (OME). When the films were suggestive of infection, maxillary sinus washouts were carried out as part of the surgical treatment. Abnormal X rays were obtained in 28 per cent of the study group, but only 16 cases (seven per cent) of sinus infection were confirmed on antral lavage. In those with positive washouts, there was an apparent relationship between the findings in the maxillary sinuses and middle ears of the same side in some of the cases. There was also evidence of improvement of the middle ear disease when the sinus infection was successfully treated. It does not appear that sinus infection is an important cause of OME, though it may be relevant in a small number of cases. PMID- 7989828 TI - Hearing thresholds in insulin-dependent diabetic patients. AB - Hearing thresholds were studied in 53 patients with insulin-dependent diabetes mellitus (IDDM) and 42 randomly selected non-diabetic control subjects, aged between 20 and 40 years. The hearing level tended to be worse in diabetic patients than in control subjects, but the differences were statistically significant only at frequencies of 6,000 and 8,000 Hz. Microvascular complications (retinopathy and nephropathy), and the duration of diabetes were associated with the elevated hearing thresholds. In contrast, poor metabolic control (high fasting blood glucose and glycated haemoglobin A1c) was not associated with increased hearing thresholds. The changes caused by diabetic neuropathy appeared simultaneously with microvascular complications and a long duration of the diabetes, and thus a causative role of diabetic neuropathy in the pathogenesis of elevated hearing thresholds remained unsolved. It was concluded that elevated sensorineural hearing thresholds at the frequencies of 6,000 and 8,000 Hz in patients with IDDM are probably caused by the long duration of diabetes and the microvascular complications associated with it. PMID- 7989830 TI - Microscope and hot wire cautery management of 100 consecutive patients with acute epistaxis--a superior method to traditional packing. AB - The technique of microscope examination and hot wire cautery in a prospective study of 100 consecutive patients with acute epistaxis is described. The method was successful in arresting haemorrhage in 94 per cent of patients bleeding at the time of examination, and in 86 per cent, discharge home within one hour was possible. Due to improved illumination, magnification and control of the cautery instrument, nasal packing was required in only nine per cent of cases. By achieving this and by reducing the overall need for admission to 20 per cent, we recommend this method of treatment both as a successful cost saving measure, as well as advantageous to the patient. PMID- 7989832 TI - A pneumatic artificial larynx popularized in Hong Kong. AB - The 'Taiwan tube' is an inexpensive pneumatic artificial larynx made in Taiwan. The device, which is a tracheo-oral shunt containing a resonator, is popular with laryngectomees in Hong Kong. This paper reports its use and describes its working dynamics which compare favourably with those of other forms of voice restoration. PMID- 7989831 TI - Serum adenosine deaminase and total superoxide dismutase activities before and after surgical removal of cancerous laryngeal tissue. AB - In this study, pre- and post-operative serum activities of adenosine deaminase (ADA) and total superoxide dismutase (SOD) enzymes were measured in patients with squamous cell laryngeal cancer. Activities of both enzymes were found to be higher in cancerous patients compared to the controls. No significant differences were found however between pre- and post-operative values for both enzymes in the patient group. It has been suggested that ADA and SOD enzymes leak from the cancerous laryngeal tissues into the blood stream. The absence of differences between pre- and post-operative serum enzyme activities has two possible explanations: Firstly, removal of previously released enzymes from the blood stream takes a much longer period than one month; and secondly, cancerous laryngeal tissue is not the only source of the enzymes mentioned even after removal of cancerous tissue by surgical operation, other sources such as adjacent tissues and/or metastatic tissues etc, still release these enzymes into the blood stream. PMID- 7989833 TI - The hyoid syndrome: a pain in the neck. AB - This paper reports on 13 patients with a pain syndrome arising from the region of the greater cornu of the hyoid bone. It is often missed and yet is readily treatable. The syndrome causes pain on swallowing in the region of the hyoid which may radiate to the ear, face and lower jaw or may be felt also in the pharynx. Treatment by an injection of a mixture of depomedrone and one per cent lignocaine is very effective. The underlying pathology is discussed and it is suggested that in some cases the pain and discomfort experienced by patients may be due to tenosynovitis of the intermediate tendon of the digastric muscle. Greater recognition of this relatively common condition would not only result in more effective treatment but would also avoid unnecessary investigation and surgery. PMID- 7989834 TI - A comparison of cellular proliferation markers in squamous cell carcinoma of the head and neck. AB - Head and neck squamous cell carcinoma has a relatively good prognosis but treatment may be at the expense of function and quality of life. Various host and tumour parameters have been studied in an attempt to predict the course of the disease but without success. It has been hoped that laboratory based methods, particularly those based on molecular biology, may prove more useful. Cell kinetic parameters are studied in this paper. The present study includes 75 patients with a proven squamous cell carcinoma of the head and neck at various sites and undergoing various forms of treatment. The patient's mean age was 62 years and the median survival rate 45 months. Immunohistochemical techniques using Ki67 and PCNA were compared with flow cytometric analysis which included the BRDU labelling index, the duration of S phase, ploidy and potential doubling time. The median PCNA index was 560 and the Ki67 index 298. These indices varied between 980 and 150 for PCNA and 808 and 110 for Ki67. The BRDU labelling index measured by flow cytometry was 8.9 with a range from 25 to 1.6 and the duration of S phase was 14.8 hours. The PCNA index failed to correlate with any host or tumour factors and this failure was also seen in Ki67 indices and also in the flow cytometric parameters. There was a strong correlation between PCNA and Ki67 expression (p < 0.0001). Neither PCNA nor Ki67 values were significantly different between irradiated and nonirradiated tissues nor in sites or in patients who later developed lymph node metastases.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7989835 TI - Sedation with a target-controlled propofol infusion system during assessment of the upper airway in snorers. AB - The ability of a target-controlled propofol infusion system to provide sedation for patients undergoing assessment of the upper airway during snoring is presented. This technique provides the desired sedation level for induction of snoring and is short acting and readily controllable. We advocate its use in sedation nasal endoscopy. PMID- 7989836 TI - Primary extramedullary plasmacytoma in the middle ear: differential diagnosis and management. AB - Primary extramedullary plasmacytoma (PEP) is an uncommon neoplasm of plasma cell origin which afflicts the head and neck mainly. In this study we report a rare case of a 34-year-old man who presented with left ear tinnitus, hearing loss, blocked feeling and headache. Exploratory tympanotomy revealed a mass extending into the attic and the mastoid antrum. Following canal wall-up mastoidectomy, the tumour was carefully removed. Histological examination (including immunoperoxidase staining) and thorough clinical, laboratory and radiological evaluation revealed an exclusively cytoplasmic monoclonal IgG immunoglobulin PEP. The combination of surgery (including a second-look procedure) and radiotherapy used in this case may be an over-treatment. However, the patient is still disease free seven years after his first admission to hospital. PMID- 7989837 TI - Button battery in the nose--an unusual foreign body. AB - We present two rare, but similar, cases of button batteries in the nose in male children of Caucasian origin. The importance of early diagnosis, treatment and the long-term morbidity of such a foreign body in the nose are discussed. PMID- 7989838 TI - Acute bilateral blindness in childhood caused by rhabdomyosarcoma and malignant lymphoma. AB - Sudden unilateral visual loss in children is usually caused by a complication of acute purulent sinusitis. Differential diagnosis must include malignant tumours of the orbit or the paranasal sinuses involving the optic nerve. Rapid and adequate diagnostic measures are required in this emergency situation. In comparison, acute or progressive bilateral blindness is a very rare disorder. We report two cases of bilateral visual loss caused by malignant tumours and diagnostic and therapeutic strategies are described. Our reports show that these life-threatening disorders and their severe complications can be managed successfully if well-coordinated interdisciplinary cooperation is conducted from the beginning. If surgery is performed in this vulnerable region, it may be facilitated by computer-aided modelling techniques. During the last decade the prognosis for rhabdomyosarcoma and malignant lymphoma, the most frequent mesenchymal tumours of childhood, has improved dramatically. Thus, any loss of time causing a delay in correct diagnosis and the onset of adequate therapy must be avoided. Intensive cooperation with paediatric oncologists has to be enlisted from the beginning to avoid unnecessary, repetitive, invasive, or imaging diagnostics and to accelerate the onset of specific therapy. PMID- 7989839 TI - Recurrent laryngeal nerve palsy secondary to benign thyroid disease. AB - A recurrent nerve palsy occurring in the presence of a goitre is considered to be caused by thyroid malignancy until proven otherwise. Three cases are described in which benign thyroid disease resulted in recurrent laryngeal nerve paralysis. Recent haemorrhage was implicated histologically as the possible aetiology in all three cases. The importance of identifying and preserving the recurrent laryngeal nerve in the surgical management is highlighted. PMID- 7989840 TI - The carcinogenic risk of exposure to sulphuric acid fumes from lead acid batteries. AB - Prolonged exposure to sulphuric acid fumes is associated with an increased risk of developing laryngeal carcinoma. Lead acid batteries are a potential source of these fumes. We present a case of an electric fork lift truck driver who developed laryngeal carcinoma as a result of such exposure. PMID- 7989841 TI - Aspergillosis of the larynx. AB - Primary infection of the larynx with Aspergillus spp. is rare. It is more commonly seen as part of a wider infection involving the respiratory system in an immunocompromised host. In noncompromised patients laryngeal aspergillosis may represent colonization rather than invasion requiring no systemic anti-fungal treatment. The diagnosis is important as the presenting symptoms are suggestive of malignant laryngeal disease. We present a 62-year-old man with a short history of hoarseness. Direct laryngoscopy and biopsy confirmed the diagnosis of aspergillosis. Clinical presentation, diagnosis and the important pathological characteristics of this infection are discussed. PMID- 7989842 TI - Thyroid metastasis from nasopharyngeal carcinoma: a case report. AB - Anaplastic nasopharyngeal carcinoma (NPC) metastatic to the thyroid gland is rare. We report the first such case in a 54-year-old Malaysian Chinese woman. The correct diagnosis should be made so that thyroidectomy may be avoided and an appropriate chemoradiotherapeutic regimen instituted. PMID- 7989843 TI - Highly invasive papillary thyroid carcinoma. AB - Papillary carcinoma is the most common malignant tumour of the thyroid gland, accounting for at least two-thirds of newly diagnosed carcinomas. This tumour may be occasionally multicentric in origin. It frequently spreads to regional lymph nodes in the neck and mediastinum, but uncommonly metastasizes outside these regions. Local invasion of this tumour to the upper airway or digestive tract structures is infrequent. However, when that occurs, it is a source of significant morbidity and mortality. In the last two years four patients suffering from invasive papillary carcinoma to the aerodigestive tract were treated in our department. A short case history of one of them is presented and current trends in management of the disease are reviewed. PMID- 7989844 TI - Parotid haemangiomas in childhood: a case for MRI. AB - Seven infants with unilateral parotid haemangiomas seen at one centre are presented. Their case notes and special investigations are reviewed. Magnetic resonance imaging (MRI) is revealed as the investigation of choice because of picture quality, definition of soft tissues and lack of exposure to ionizing radiation. MRI allows a definite diagnosis to be made without any invasive procedure being required. A future study following up these infants may be of interest because of controversy regarding the spontaneous resolution of these lesions. PMID- 7989845 TI - Squamous cell carcinoma of the maxillary antrum metastatic to the heart and skin. AB - A case of squamous cell carcinoma of the maxillary antrum is presented in which autopsy examination revealed wide-spread disseminated disease including metastatic deposits in the unusual sites of the myocardium and skin. Apart from the skin deposit the metastases were clinically unsuspected. This case demonstrates the role of the autopsy in the study of malignancy and the possible effects of local disease control on the natural history of the disease process. PMID- 7989846 TI - Pulmonary carcinoma metastatic to the larynx. AB - Metastases to the larynx from distant primaries are rare. We report a case of a pulmonary epidermoid carcinoma metastatic to the larynx that simulated a primary cancer. A review of the literature showed nine previously reported cases of pulmonary metastases to the larynx--only two of them were epidermoid carcinomas. Treatment of a secondary lesion in the larynx is justified only when other organs have not been affected. The diagnostic and therapeutic considerations of this condition are discussed. PMID- 7989847 TI - Parotid acinic cell carcinoma with undifferentiated spindle cell transformation. AB - This report describes a 59-year-old black man who had an acinic cell carcinoma with associated malignant spindle cell transformation in the parotid gland. To the best of our knowledge, a similar lesion in the salivary gland has not been previously reported. PMID- 7989848 TI - Angiosarcoma of the hypopharynx. AB - Angiosarcoma is a tumour of endothelial origin rarely found in the head and neck. A case of angiosarcoma of the pyriform sinus, treated by surgery and post operative radiotherapy, is reported, providing a cue for discussion of the diagnostic, clinical and pathological peculiarities of the tumour in the light of personal experience and the published data. PMID- 7989849 TI - Pre-operative haemoglobin estimation is essential. PMID- 7989850 TI - Uvulectomy to prevent throat infections. PMID- 7989851 TI - Homework for students with learning disabilities: the implications of research for policy and practice. AB - The literature on homework for students with learning disabilities is reviewed. First, a summary of Cooper's (1989a) synthesis of research on homework for students without disabilities is presented, including (a) a definition of homework, (b) a model of the homework process, (c) the results of a meta-analysis of homework studies, and (d) generic policy guidelines. Next, special education research on homework conducted after 1985 is described. The literature is divided into studies that manipulated homework conditions and homework-related surveys of teachers and parents. The results of the literature review suggest that homework policies and practices for students with learning disabilities should emphasize (a) simple, short assignments; (b) careful monitoring by and prominent rewards from teachers; and (c) parental involvement, especially to provide structure, conducive environments, and immediate rewards. PMID- 7989852 TI - Homework: a survey of policies in the United States. AB - Homework is a key area of concern in our nation's public schools, as well as a central element of collaboration between home and school. The purpose of the current study was to survey the policies of a national sample of school districts concerning homework. Specific foci of the survey included whether a homework policy had been instituted, if modifications were made in the policy for students with disabilities, the types of homework, the length and frequency of assignments given, and specific communication mechanisms between home and school. A total of 550 surveys were mailed, with a response rate of 48.5%. The results indicated that only 35.2% of school divisions did have a policy on homework, with 64.4% of those policies including modifications for students with disabilities. Findings in terms of frequency and amount of homework assigned, as well as home-school communication mechanisms, are highlighted. The results are discussed within the context of policy development and instructional implications. PMID- 7989853 TI - Doing homework: perspectives of elementary and junior high school students. AB - A survey of homework experiences was administered to 1,527 elementary and junior high students in regular (n = 1,242), resource (n = 234), and self-contained special education (n = 51) classrooms. The results found significant main effects for Group, Grade, and Group by Grade interactions for items related to amount of, type of, and time spent doing homework; opportunity to do homework at school; parents' assistance; students' beliefs about homework assignments and grading; and students' feelings about homework and school. The higher incidence of negative feelings and opinions from students in resource room programs suggests that students' understanding of assignments, the nature of the assignments, and the feedback given to students are important issues requiring closer evaluation. The results also suggest that changes in homework assignments and grading may make the transition from elementary to junior high school particularly difficult for students with special needs. PMID- 7989854 TI - Homework practices of general education teachers. AB - The purpose of this study was to survey the homework practices of general education teachers who teach students with disabilities. A national sample of 441 elementary, middle, and senior high teachers were asked about their homework practices, including their use of adaptations for students with disabilities. The results highlight homework practices and adaptations that are used frequently and perceived by teachers as helpful for students with disabilities. Also discussed are the differences in practices and adaptations across elementary, middle, and high school teachers, as well as the instructional implications of the identified homework practices for students with disabilities and their general education teachers. PMID- 7989855 TI - Mathematical outcomes of attention-deficit hyperactivity disorder. AB - We assessed the academic performance and behavior of 121 nondisabled elementary boys and 107 boys with attention-deficit hyperactivity disorder (ADHD), ages 7.4 through 14.5 years. Students completed computer-generated tasks of reading, computation, and math problem solving, and we recorded two performance measures (accuracy and speed) and three behavioral measures (vocalizations, head movements, and bottom movements). Our purpose was to determine the effects of ADHD on conceptual and computational math. For greater precision than has been available in past math research, we held reading and problem structure constant, while recording speed of processing, number recognition, and motor response. Our analysis yielded significantly lower problem-solving scores in specific math concepts and slower computational performance for the boys with ADHD. These findings demonstrated the educational implications of attention deficit disorders for mathematical skill and the need for interventions that are geared more specifically to these deficits, and that also provide accommodations for reading complexity and length, visual-motor skill, feedback, and self-pacing. PMID- 7989857 TI - Collaborative teacher roles: special and general educators. AB - The purpose of this study was to analyze and compare the perceptions of a national sample of elementary-level learning disabilities resource teachers (n = 83) and elementary general education teachers (n = 64) in regard to actual and ideal performance of collaborative roles. Resource teacher perceptions of constraints on their performance of collaborative roles also were examined. Results indicated significant differences between teacher perceptions of actual and ideal performance of collaborative roles. Constraints on resource teachers' collaborative role performance were identified. PMID- 7989856 TI - Neurolinguistic differentiation of children with subtypes of dyslexia. AB - A detailed analysis of the types of childhood dyslexia proposed by Boder (1973) and Bakker (1990) revealed characteristic patterns of organization of intellectual functions, of hemispheric specialization, and of reading errors in right-handed children with dyslexia. Children with L-type dyslexia (10 subjects) evidenced a large number of reading errors (e.g., substitutions of nouns and verbs), low scores in verbal short-term memory, and right-ear advantage (REA) in dichotic listening. Children with P-dyslexia (18 subjects) evidenced few reading errors, a short attention span, low performance in visual-motor coordination (WISC-R coding), and an absence of REA in dichotic listening. Children with M type dyslexia (10 subjects) showed numerous reading errors (e.g., substitution of syllables and words), low performance in visual-motor coordination items (coding), and REA in dichotic listening. PMID- 7989858 TI - Oxolanosterol oximes: dual-action inhibitors of cholesterol biosynthesis. AB - A series of oxolanosterol oximes and oxime ethers have been prepared as potential dual-action inhibitors of cholesterol biosynthesis. The synthesis of these oximes along with the evaluation of their ability to inhibit lanosterol 14 alpha-methyl demethylase (P450DM) and to suppress 3-hydroxy-3-methylglutaryl coenzyme. A reductase (HMGR) activity is presented. 3 beta-Hydroxylanost-7-en-15-one 15-oxime XIX was found to be an effective inhibitor of P450DM in rat liver microsomal preparations. In [14C]acetate incorporation studies using Chinese hamster ovary (CHO) cells, compound XIX was found to cause a dramatic reduction in the incorporation of acetate into C27 sterols with a concomitant increase in radiolabeled C30 sterols which is consistent with the inhibition of P450DM. In addition, 15-oxime XIX was shown to suppress HMGR activity in both wild-type CHO and P450DM-deficient (AR45) cells, indicating that suppression of HMGR is independent of any effects of this oxime on P450DM. In both cell lines, parallel declines in HMGR activity and HMGR protein levels were observed suggesting that compound XIX suppresses HMGR activity by regulation of gene expression. These results demonstrate that, as predicted, 15-oxime XIX is indeed a dual-action inhibitor of cholesterol biosynthesis which causes both the inhibition of P450DM and a reduction in HMGR activity. PMID- 7989859 TI - Expression of heterologous human apolipoprotein E by J774 macrophages enhances cholesterol efflux to HDL3. AB - Expression of apolipoprotein (apo) E by macrophages is tightly regulated by cellular cholesterol content. We have investigated a potential modulating role for apoE on macrophage cholesterol homeostasis by stably transfecting the J774 macrophage, which does not express its endogenous apoE gene, with a human apoE cDNA expression vector and comparing cholesterol homeostasis in this cell line with that of a control line transfected with the neomycin resistance construct only. Incubation in serum-free medium after cholesterol loading produced no difference in cellular cholesterol content between apoE secreting and non secreting J774 cells. Similarly, in serum-free medium there was no difference in the amount of radiolabeled cholesterol effluxed. Addition of cAMP or S58035 to cholesterol-loaded J774 cells did enhance efflux of radiolabeled cholesterol from apoE secreting compared to non-secreting macrophages but did not detectably alter cellular free cholesterol or cholesteryl ester mass. Incubation with HDL3 alone, however, significantly decreased macrophage cholesteryl ester mass compared to a 24-h incubation in serum-free medium from 10.5 +/- 3.9 to 3.2 +/- 2.0 (P < 0.01) in apoE-secreting J774 cells. During a 24-h incubation in HDL3, cholesteryl ester fell from 6.4 +/- 2.4 to 0.8 +/- 0.7 (delta = 5.6 micrograms/mg) in apoE secreting cells and from 9.3 +/- 2.2 to 7.7 +/- micrograms/mg (delta = 1.6 micrograms/mg) in non-secreting cells (P < 0.005 apoE-secreting vs. non-secreting cells).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7989860 TI - Overfeeding increases very low density lipoprotein diameter and causes the appearance of a unique lipoprotein particle in association with failed yolk deposition. AB - Structurally specific very low density lipoprotein (VLDL) particles are presumed to redirect VLDL uptake during yolk deposition. Egg production is an energy intensive process, but energy excess negatively affects egg production. This study sought to determine whether overfeeding changed hen lipoprotein profiles, and if so, whether changes were related to egg production. Overfeeding caused 33% of hens to stop yolk deposition and reabsorb unovulated follicles (involute). VLDL of control hens possessed characteristic small particle size (30 nm) and composition indicative of limited intravascular metabolism. Overfeeding generally increased VLDL diameter, the effect being slight (+6.6 nm) in overfed laying hens when compared to overfed-involuted hens (+51.2 nm). Changes in composition indicated that increased intravascular metabolism of VLDL parallelled increases in particle diameter. Overfed-involuted hens showed significant elevations of plasma low density lipoprotein, VLDL cholesteryl ester, and high density lipoprotein (HDL) triacylglycerol content. Overfeeding increased plasma HDL, and in association with involution, caused redistribution of HDL particle sizes, including the appearance of novel HDL approximately 20 nm in diameter, termed HDLR, and a 97 kDa protein within the HDL fraction. The overfed hen model may provide new insight into the role of lipoprotein physical properties in determining the metabolism of triacylglycerol-rich lipoprotein, and the process of reverse lipid transport. Overfeeding generally increases VLDL size and plasma HDL levels suggesting that increased peripheral metabolism, and perhaps mechanical exclusion of enlarged VLDL by the granulosa basal lamina, contribute to the obesity and impaired yolk deposition observed in hens with excessive energy intakes. Temporal definition of massive VLDL enlargement relative to follicular collapse remains to be established.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7989861 TI - Possible compensation of structural and viscotropic properties in hepatic microsomes and erythrocyte membranes of rats with essential fatty acid deficiency. AB - The effect of essential fatty acid deficiency on the structural and dynamic properties of the lipid matrix of rat liver microsomes and erythrocyte membranes was studied. The rate and range of the rotational mobility of 1,6-diphenyl-1,3,5 hexatriene and 2-, 7-, and 12-(9-anthroyloxy)stearate probes in the native membranes and in lipid vesicles prepared with the total lipid extracts of these membranes were evaluated by using differential polarized phase fluorometry. For the anthroyloxystearate probes, two modes of rotation (in and out of the plane of the aromatic anthracene ring) were partially resolved by measuring at different excitation wavelengths. The fat-free diet produces important changes in the fatty acid composition of the different glycerophospholipid classes without affecting the total double-bond number, the relative contents of cholesterol, phospholipid, and protein, and the glycerophospholipid class distribution. The principal changes, more pronounced in liver microsomes than in erythrocytes, are: an increase in nonessential monoene and triene (18:1n-9 and 20:3n-9) and a decrease in essential diene (18:2n-6) and tetraene (20:4n-6). These changes modify the double-bond distribution as a function of the distance from the interphase toward the bilayer interior, with a significant deficit (15% in erythrocytes and 30% in liver microsomes) in the double-bond density in the intermediate region of the membrane leaflet, corresponding to the carbon number 11-12 of an extended saturated acyl chain, and where the 12-anthroyloxystearate probe is located. In spite of the changes in fatty acid composition and double-bond distribution, with the only exception of a slight increase (about 15%) in the "out of the plane" rotation rate of the 7-(9-anthroyloxy)stearate probe in the erythrocyte lipid vesicles, no other significant change is observed. Thus, the changes in fatty acid composition would take place in such a way that at least the average structural and viscotropic properties of the lipid phase of the membrane, sensed by these probes, would be almost exactly compensated. PMID- 7989862 TI - Distribution of angiotensin II receptors in rat and human adipocytes. AB - Angiotensin II (AII) receptor binding assays were performed in rat adipocytes from three separate anatomic depots. Fat cells were isolated by collagenase digestion, and plasma membranes were prepared from the epididymal, mesenteric, and retroperitoneal fat depots of male Sprague-Dawley rats at 100 days of age. Binding of 125I-labeled [Sar1,Ile8]AII was rapid, saturable, and specific in membranes from all depots, identifying a receptor with a similar affinity of approximately 1 nM. Site-associated differences in receptor number were observed, with epididymal and mesenteric fat cell membranes exhibiting significantly more receptors than retroperitoneal fat cells when binding was expressed per unit of membrane protein. When corrected for cell volume, the number of receptors per cell ranked epididymal > retroperitoneal > mesenteric. Inhibitory constants for the peptide agonists AII and AIII and the peptide antagonist [Sar1,Ala8]AII indicated similar affinities in all three depots. Because the receptor has been classified pharmacologically into two subtypes, the AT1 selective antagonist losartan, and the AT2 selective antagonist PD 123,319 were used to classify the adipocyte receptor, indicating an AT1 subtype with an affinity for losartan in the mesenteric and retroperitoneal adipocytes that was significantly greater than the epididymal. Similar studies were performed in adipocyte membranes obtained from human omental and subcutaneous adipose tissue, revealing the presence of an AII receptor in both depots with an affinity of approximately 10 nM for losartan. These data indicate site-specific differences in AII receptor number in fat cell membranes from rats and the existence of human adipocyte AII receptors, suggesting that the adipocyte is significant for the peripheral metabolism of components of the renin-angiotensin system. PMID- 7989863 TI - Separation of subfractions of the hydrophobic components of calf lung surfactant. AB - This study reports the biochemical separation of the hydrophobic constituents of calf lung surfactant into separate fractions from which specific components are excluded. Gel permeation chromatography on LH-20 with acidified chloroform methanol separated the constituents of calf lung surfactant extract (CLSE) into fractions containing purified phospholipids (PPL), the neutral lipids and phospholipids (N&PL), or the hydrophobic surfactant proteins (SP)-B and -C together with the phospholipids (SP&PL). Extraction of acid to prevent phospholipid degradation after separation reduced recovery of the apoproteins in SP&PL. This fraction was therefore supplemented with protein purified separately to attain the initial levels present in CLSE. Biochemical analyses confirmed that the resulting preparations had the expected composition not only of protein, neutral lipids and phospholipids, but also of the phospholipid head groups. In addition to these fractions obtained with acidified solvent, elution of CLSE with chloroform-methanol without acid yielded the zwitterionic phospholipids substantially depleted of anionic phosphatidylglycerol and phosphatidylinositol. Limited interfacial measurements also demonstrated that the process of separation did not alter the fundamental surface characteristics of the surfactant constituents. Recombined CLSE (rCLSE) reconstituted from all of the separated components had surface activity indistinguishable from the original CLSE. The individual fractions of surfactant components also had average molecular areas at the air-liquid interface which agreed with predictions based on their biochemical composition. These well defined preparations of the hydrophobic constituents of pulmonary surfactant provide the basis for future studies to establish the role of individual components in the function of this complex surface active material. PMID- 7989864 TI - Stimulation of fatty acid oxidation by a 3-thia fatty acid reduces triacylglycerol secretion in cultured rat hepatocytes. AB - The present work shows that when mitochondrial beta-oxidation is stimulated by the hypolipemic, non-beta-oxidizable fatty acid analogue tetradecylthioacetic acid, there is a decrease in the secretion of triacylglycerol in cultured rat hepatocytes. In order to study the effects of tetradecylthioacetic acid in cells with different fatty acid oxidation rates, cells were grown without or with L carnitine supplement or with addition of the beta-oxidation inhibitor L aminocarnitine. In cells grown without and with L-carnitine in the medium, the oxidation of [1-14C]oleic acid was stimulated by tetradecylthioacetic acid, whereas it was not significantly changed by palmitic acid. In cells grown with L aminocarnitine, oxidation of [1-14C]oleic acid was almost abolished both in the absence and in presence of tetradecylthioacetic acid. The effect of tetradecylthioacetic acid and palmitic acid on incorporation of [1-14C]oleic acid into triacylglycerol was similar under all conditions. In the presence of L carnitine, secretion of oleic acid-labeled triacylglycerol was reduced significantly more by tetradecylthioacetic acid than by palmitic acid. The effects of tetradecylthioacetic acid and palmitic acid on secretion of oleic acid labeled triacylglycerol were reversed in cells grown with L-aminocarnitine, where palmitic acid was the stronger inhibitor. These results were substantiated by determination of mass of triacylglycerol secreted. It is concluded that tetradecylthioacetic acid reduces secretion of triacylglycerol from rat hepatocytes mainly by acutely stimulating fatty acid oxidation. PMID- 7989865 TI - Vesicles and mixed micelles in hypothyroid rat bile before and after thyroid hormone treatment: evidence for a vesicle transport system for biliary cholesterol secretion. AB - Hypothyroid rats show reduced secretion of biliary lipids, especially cholesterol. Secretion of biliary cholesterol is markedly augmented to levels above euthryroid beginning 12-24 h after administration of thyroid hormone. In the current studies, bile from hypothyroid and triiodothyronine-treated chronic bile-fistula rats was analyzed for vesicles and mixed micelles by metrizamide gradient ultracentrifugation. For euthryoid and hypothyroid animals, less than 12% of biliary cholesterol was in a vesicle gradient fraction. After treatment with triiodothyronine, biliary cholesterol increased markedly, and 50% of total cholesterol, 60% of excess cholesterol secreted, appeared in the vesicle fraction. Triiodothyronine stimulation of vesicle secretion resulted in cholesterol-rich vesicles (cholesterol:phospholipid ratio rose from less than 0.1 to 0.56), but no change in the distinct fatty acid composition of vesicle phospholipids. The microtubule inhibitor colchicine, given 12 h after triiodothyronine, prevented subsequent increase in cholesterol secretion in the form of vesicles. These studies, in a model that allows rapid changes in biliary lipid secretion, support the hypothesis that an important component of cholesterol and phospholipid secretion into bile involves microtubules and may involve a vesicle pathway. PMID- 7989866 TI - Partial duplication of the EGF precursor homology domain of the LDL-receptor protein causing familial hypercholesterolemia (FH-Salerno). AB - A novel mutation of low density lipoprotein (LDL)-receptor gene was found in an Italian family hypercholesterolemia (FH) patient during a screening of 300 FH patients. The proband as well as her daughter were found to be heterozygotes for the mutation. Binding, internalization, and degradation of 125I-labeled LDL by the proband's fibroblasts were reduced to approximately 50% compared to values found in control cells. DNA analysis by Southern blotting showed that the mutant allele was characterized by an insertion of about 10 kb, which resulted from a duplication of exons 9-14 of the LDL-receptor gene. In addition, Northern blot analysis of the proband's RNA showed, besides the normal sized LDL-receptor mRNA (5.3 kb), an additional mRNA of about 6.2 kb. The junction between exon 14 and the duplicated exon 9 was amplified by polymerase chain reaction (PCR) from the cDNA. The sequence of the amplified fragment showed that exon 14 joined the duplicated exon 9 without changing the reading frame. The derived amino acid sequence indicated that the mutated receptor protein had a partial duplication of the EGF precursor homology domain. Ligand and immunoblotting revealed that proband's fibroblasts contained one-half of the normal amount of LDL-receptor protein (molecular mass 130 kDa) and an abnormally large receptor of approximately 160 kDa. The amount of this abnormal receptor as detected by two monoclonal antibodies (10A2 and 4B3) was found to be approximately 30% that of the normal LDL-receptor present in the same cells.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7989867 TI - Electrophoretic screening for genetic variation in apolipoprotein C-III: identification of a novel apoC-III variant, apoC-III(Asp45-->Asn), in a Turkish patient. AB - Screening of 6,840 plasma samples by isoelectric focusing (IEF) led to the identification of a novel apolipoprotein C-III variant. The underlying molecular defect was established by sequencing of exons 3 and 4 of the apoC-III gene subsequent to their amplification by the polymerase chain reaction (PCR). A G-->A transition in the first nucleotide of codon 45 results in a replacement of aspartic acid by asparagine. ApoC-III(Asp45-->Asn) was detected in a Turkish patient who previously had undergone coronary bypass surgery. Family studies identified two of the three children of the index patient as heterozygous variant carriers. The family was too small to demonstrate a significant effect of the variant on lipid metabolism. However, as judged by two-dimensional immunoelectrophoresis as well as IEF and subsequent scanning densitometry, the concentrations of the variant allele products were increased twofold in very low density lipoproteins (VLDL) and slightly decreased both in low density lipoproteins (LDL) and in high density lipoproteins (HDL) relative to the concentrations of the normal allele products. The disproportional distribution of the variant apoC-III isoproteins may indicate differences in the metabolism of variant and normal apoC-III. We conclude that genetically determined structural variants of apoC-III with changes in complete net charges are very rare and, hence, do not significantly contribute to the formation of dyslipidemia in the German population. Although heterozygosity for apoC-III(Asp45-->Asn) is not associated with severe dyslipidemia, the disproportional distribution of the allele products among plasma lipoproteins indirectly indicates some impact on lipoprotein metabolism. PMID- 7989868 TI - Hydrolysis of a novel lysosomotropic enzyme substrate for beta-galactosidase within intact cells. AB - With the goal of improving the detection of lysosomal sphingolipid hydrolases within intact cells, we have recently synthesized a new fluorophor, O-[4-(1 imidazolyl)butyl]-2,3-dicyano-1,4-hydroquinonyl beta-D-galactopyranoside (Im-DCH beta-Gal). In the present study, we evaluated the interaction of Im-DCH-beta-Gal and its tetraacetate derivative, Im-DCH-beta-Gal(OAc)4, with living human fibroblasts. Im-DCH-beta-Gal was shown to be a specific substrate for human lysosomal beta-galactosidase in cell homogenates. Im-DCH-beta-Gal(OAc)4 was taken up and hydrolyzed by normal fibroblasts under physiological culture conditions. Very little hydrolysis of Im-DCH-beta-Gal(OAc)4 was observed in fibroblasts genetically deficient in lysosomal acid beta-galactosidase or in normal cells pretreated with the lysosomal inhibitors chloroquine and ammonium chloride. Analysis of substrate processing by cells indicated that normal and acid beta galactosidase-deficient cells showed similar rates of uptake and deacetylation of Im-DCH-beta-Gal(OAc)4, with an 80% decrease in the rate of deglycosylation of substrate by beta-galactosidase-deficient fibroblasts. However, under our conditions, the fluorescent product was not well retained by cells. Our results indicate that this novel class of compounds may be useful in measuring lysosomal enzyme function in intact cells and may have application as a fluorescent marker for genetically altered cells. PMID- 7989869 TI - Occurrence of sulfoquinovosyl diacylglycerol in some members of the family Rhizobiaceae. AB - A radiolabeled component of a membrane extract of Rhizobium meliloti 2011 cells grown in the presence of 35S-labeled sulfate was isolated by silica flash chromatography and purified by high performance liquid chromatography (HPLC). Based on 1- and 2-dimensional nuclear magnetic resonance (NMR) spectroscopic and mass spectrometric analyses, the structure of the compound was determined to be sulfoquinovosyl diacylglycerol (SQDG). NMR analyses indicated substantial heterogeneity in the fatty acid composition and that an important group was the cyclopropyl fatty acids. This first report of the occurrence of SQDG outside of the plant kingdom, photosynthetic bacteria or diatoms deserves special attention as, in this case, the bacterium is one that can fix nitrogen in symbiosis with plants. The origins of the bacterium's ability to synthesize this class of membrane lipids is an important question. Membrane extracts of other strains of the family Rhizobiaceae were screened for the presence of SQDG. The occurrence of SQDG in the symbiotic organisms was confirmed, while no SQDG was detected in either the Agrobacterium tumefaciens or the Escherichia coli strains tested. The current function of these lipids in symbiosis and the commonality of the ability of bacteria that function as plant symbionts to synthesize such molecules are all germane to studies of the Rhizobium/legume symbiosis. PMID- 7989870 TI - Effects of lovastatin and chenodiol on bile acid synthesis, bile lipid composition, and biliary lipid secretion in healthy human subjects. AB - To assess the relationship between cholesterol synthesis and feedback inhibition of bile acid synthesis, we studied seven normal human subjects taking three different doses of chenodiol, 0, 5, and 15 mg/kg per day: once while taking no lovastatin and again while taking lovastatin 80 mg/day. Lovastatin and both doses of chenodiol significantly lowered bile acid synthesis measured by the 14CO2 method, but there was no significant interaction between the perturbations. Both also lowered cholesterol saturation index of gallbladder bile without appreciable interaction, and the combination was distinctly more effective than either medication alone. Lovastatin and low-dose chenodiol both lowered biliary cholesterol secretion without affecting bile acid secretion. Increasing the dose of chenodiol did not further lower cholesterol secretion, but did further reduce saturation index because of an increase in secretion of bile acid and phospholipid. These studies indicate that there is no interaction between cholesterol synthesis and feedback return of bile acid in the enterohepatic circulation with respect to either bile acid synthesis or biliary lipid secretion; that the combination of chenodiol and lovastatin is better than either alone for improving biliary cholesterol saturation; and that the mechanism by which chenodiol lowers cholesterol saturation is dose-dependent. PMID- 7989871 TI - Isolation of allele-specific, receptor-binding-defective low density lipoproteins from familial defective apolipoprotein B-100 subjects. AB - Familial defective apolipoprotein B-100 (FDB) is a genetic disorder apparently caused by a single amino acid substitution (Arg3500-->Gln) that disrupts the binding of low density lipoproteins (LDL) to the LDL receptor. The plasma of FDB heterozygotes contains a mixture of normal LDL and LDL that is defective in binding to the LDL receptor. In this study, the monoclonal antibody MB19 (which recognizes an immunogenetic polymorphism in apolipoprotein B-100) was used to determine the percentage of defective LDL in the plasma of FDB heterozygotes and to isolate allele-specific receptor-binding-defective LDL. Several FDB heterozygotes were identified who were heterozygous for the MB19 polymorphism: one apolipoprotein B allotype in each of these individuals bound with low affinity to MB19 and possessed the Arg3500-->Gln mutation, whereas the other apolipoprotein B allotype bound with high affinity to MB19 and normally to the LDL receptor. Using MB19 radio-immunoassay, we determined that an average of 73% (range 65-87) of the total LDL from FDB heterozygotes contained the Arg3500-->Gln mutation. Antibody MB19-Sepharose immuno-affinity chromatography was used to separate the receptor-binding-defective LDL from the normal LDL. The isolated LDL contained primarily the Arg3500-->Gln mutation and had only about 9% of normal LDL receptor-binding ability. Finally, the MB19-Sepharose chromatography procedure may be useful for isolating other allele-specific LDL that have functionally significant mutations. PMID- 7989872 TI - REPR and complementation factor(s) interact to modulate rat apolipoprotein B mRNA editing in response to alterations in cellular cholesterol flux. AB - Apolipoprotein B (apoB) mRNA editing is a post-transcriptional cytidine deamination involving several protein factor(s), one of which has recently been cloned. We have examined the effects of alterations in cellular cholesterol flux in the rat liver and small intestine as a means of dissecting the physiologic mechanisms regulating apoB mRNA editing, both in vivo and in isolated S-100 extracts. Hepatic cholesteryl ester accumulation was produced by feeding rats a high cholesterol diet, alone, or in combination with either ethinyl estradiol treatment, or after induction of hypothyroidism. Endogenous hepatic apoB mRNA editing decreased in parallel with the increase in cellular cholesteryl ester content (r = -0.948, P < 0.001). None of these conditions altered endogenous intestinal apoB mRNA editing. Hepatic S-100 extracts demonstrated decreased in vitro apoB RNA editing activity, in parallel with the changes observed in vivo. By contrast, the activity of intestinal S-100 extracts demonstrated a paradoxical increase in hypothyroid rats and a similar, paradoxical decrease in hyperthyroid rats, when compared to controls. Hepatic REPR mRNA, quantitated by RNase protection assay, showed a 25-50% decrease in cholesterol-fed rats. The editing activity of hepatic S-100 extracts prepared from cholesterol-fed, hypothyroid rats was restored to control levels with REPR supplementation but not with chicken intestinal S-100 extracts, suggesting that changes in REPR, but not complementation activity, may play a critical role in the regulation of apoB mRNA editing in rat liver. By contrast, the editing activity of intestinal S-100 extracts prepared from hyperthyroid animals was unaltered by supplementation with REPR, but was restored to control levels after the addition of chicken intestinal S-100 extracts. Taken together, the data suggest that tissue-specific factors regulate apoB mRNA editing in the rat and that the complex interplay of REPR and complementation factor(s) may be modulated in response to alterations in cholesterol flux, in vivo. PMID- 7989873 TI - Estimation of adipose tissue mass by magnetic resonance imaging: validation against dissection in human cadavers. AB - The evaluation of adipose tissue distribution has become an essential component of investigations on the complications of obesity. However, a major limitation is lack of methodology for accurate estimation of adipose tissue mass in the different regions of the body. Therefore, we have tested the accuracy and precision of magnetic resonance imaging (MRI) as a method to measure adipose tissue mass in regions of the body not accessible with standard anthropometric methods. The mass of subcutaneous and intraabdominal adipose tissue estimated by MRI was compared with that obtained by direct weighing of the same adipose tissue compartments after dissection in human cadavers. MRI was performed on three unembalmed cadavers (two males, one female) who were subsequently dissected to isolate intraperitoneal, retroperitoneal, and subcutaneous adipose tissues. These same components were delineated by MRI. The results of the two methods were highly congruent. For the various compartments, the mean of the difference between the two methods was only 0.076 kg (95% confidence interval + 0.005 kg and + 0.147 kg). The "limits of agreement" between the two techniques were -0.066 kg and +0.218 kg. Multiple repeated estimates of mass of adipose tissue compartments were made to determine reproducibility of the MRI measurement; the coefficient of variation for repeated measures was below 14%. The results of this study show that MRI is an accurate and precise technique to evaluate adipose tissue mass in subcutaneous and intraabdominal compartments. Furthermore, MRI was found to be a valid method to separately evaluate the mass of intraabdominal subcompartments of intraperitoneal and retroperitoneal adipose tissue. PMID- 7989874 TI - Pitfalls in the use of breath pentane measurements to assess lipid peroxidation. AB - Literature values for breath pentane, an indicator of lipid peroxidation, vary by 1,000-fold in healthy subjects. This report describes multiple technical artifacts that may explain this disparity. First, we found that a major component of human breath (probably isoprene) co-eluted with pentane on columns used by some investigators, resulting in erroneously high determinations. Second, despite washouts using pentane-free air, ambient pentane dissolved in body fat may result in breath concentrations many times greater than that due to endogenous production. True endogenous breath pentane may never have been accurately determined. PMID- 7989875 TI - Time-resolved fluorometry in the genetic diagnosis of familial defective apolipoprotein B-100. AB - A novel technique for screening point mutations has been developed for diagnosis of familial defective apolipoprotein (apo) B-100 (FDB). In FDB, an amino acid exchange occurs at position 3500 in apoB-100 due to a point mutation. Polymerase chain reaction (PCR) was performed on the appropriate region of the apoB gene, and the PCR products were hybridized in solution with europium-labeled oligonucleotides, complementary to either the wildtype or the mutant genome. The presence or absence of the apoB-3500 mutation was monitored by time-resolved fluorescence of the europium chelate. The method allows a larger number of samples to be processed simultaneously, and the detection system displays a high level of sensitivity without the hazards connected to the use of radioactivity. When 127 Swedish patients, clinically diagnosed as suffering from heterozygous familial hypercholesterolemia, were screened for the presence of the apoB-3500 mutation, two patients, unrelated to each other, were found to be heterozygotes. These patients are the first reported cases of FDB from Sweden, and the frequency rate observed among hypercholesterolemic patients, 1.6%, is in accordance with the figures reported for several other patient population in Europe and the United States. PMID- 7989876 TI - Measurement and analysis of the in vivo posteroanterior impulse response of the human thoracolumbar spine: a feasibility study. AB - OBJECTIVES: To (i) measure lumbar intervertebral motion patterns produced during low force, high frequency posteroanterior (PA) thrusts applied to adjacent thoracolumbar spinal segments; (ii) determine the dependence of PA stiffness and impedance characteristics of the thoracolumbar spine on loading frequency; and (iii) ascertain the feasibility of using PA stiffness or impedance to characterize the in vivo mechanical response of the spine during spinal manipulation. SETTING: Hospital in Gothenburg, Sweden. SUBJECTS: Three subjects- one normal (male), one patient diagnosed with L4-5 degenerative disk disease (female), and one patient diagnosed with L5 retrospondylolisthesis (male). INTERVENTIONS: Intervertebral motion device (IMD) attached to pins inserted into the L3-4 or L4-5 spinous processes. Four repeated PA impulses were delivered to each of the spinous processes (T11-L3) using an Activator Adjusting Instrument with a force-acceleration measurement system. OUTCOME MEASURES: Peak-to-peak intervertebral axial displacement, PA shear displacement and flexion-extension (FE) rotation were obtained using the IMD. Thoracolumbar PA impedance (force/velocity) vs. frequency histories and peak PA dynamic stiffness (impedance x frequency) were determined from the force-acceleration measurements. Averages and standard deviations of these measures were calculated from the repeated interventions performed at each level. MAIN RESULTS: For the normal subject, the AAI PA impulses applied to the L2 spinous process (72 +/- 9 N) produced a 1.62 +/ 1.06 mm peak-to-peak intervertebral axial displacement, 0.48 +/- 0.1 mm PA shear displacement, and 0.89 +/- 0.49 degrees FE rotation at the L3-4 spinal segment. The amplitude of the lumbar intervertebral motion in the normal subject's spine decreased approximately sixfold when the AAI impulses were delivered further from the IMD measurement site. In both patients the axial, PA shear and FE lumbar intervertebral motions were of the same magnitude, but showed less variability than the normal subject as the AAI impulses were delivered closer to the IMD measurement site. The normal thoracolumbar spine exhibited a maximum dynamic PA impedance at a frequency of approximately 100-150 Hz, resulting in a peak PA stiffness ranging from 62 KN/m (L2 segment) to 124 KN/m (T11 segment). Thoracolumbar PA stiffness values tended to be higher for the patient with a severely degenerated disk (85-362 KN/m), whereas the patient with retrospondylolisthesis had a lower PA stiffness (32-96 KN/m). CONCLUSIONS: In vivo kinematic measurements of the normal and pathologic human lumbar spine indicate that low force, PA impulses produce measurable segmental motions and reinforce the notion that mechanical processes play an important role in spinal manipulation and mobilization. Calculations of the peak dynamic stiffness derived from impedance vs. frequency measurements indicate that the dynamic stiffness of the thoracolumbar spine is considerably greater than previously reported stiffness values obtained using static and quasistatic manipulation and mobilization procedures. Computations of spinal input impedance are relatively simple to perform, can provide a noninvasive measure of the dynamic mechanical behavior of the spine, appear to have potential to discriminate pathologic changes to the spine, and warrant further study on a larger sample of normals and patients. Ultimately, chiropractic clinicians may be able to use low force, impact type spinal manipulation, together with dynamic impedance analysis procedures, to quantify the mechanical response of the normal and abnormal spine, to perform spinal diagnosis and subsequently to prescribe therapeutic treatment to patients. PMID- 7989877 TI - Further analysis of health care costs for chiropractic and medical patients. AB - OBJECTIVE: To compare the health care costs of patients who have received chiropractic treatment in insurance plans that do not restrict chiropractic or medical benefits with those treated solely by medical and osteopathic physicians. DESIGN: Retrospective statistical analysis of 2 yr of claims data on total insurance payments and total outpatient payments. OUTCOME MEASURES: Total insurance payments and total outpatient payments, each adjusted for sociodemographic characteristics. RESULTS: Patients receiving chiropractic care experienced significantly lower total health care costs as represented by adjusted third-party payments in the fee-for-service sector. Total adjusted cost differences ranged from $291 to $1722 over the 2-yr period. Total adjusted outpatient costs tended to be slightly lower for medical patients but lower hospital utilization for chiropractic patients more than offsets the additional outpatient costs associated with chiropractic care. CONCLUSIONS: The analysis of well-insured patients in plans that do not restrict the chiropractic benefit strengthens results previously reported. In this study, therefore, the favorable cost patterns for chiropractic patients cannot be attributed to insurance restrictions limiting reimbursement for chiropractic services relative to other services. Because adjustments for patient characteristics systematically reduce the cost advantages of chiropractic patients as compared to mean differences derived from unadjusted data, the results also demonstrate that adjusted values should be used for meaningful comparisons between the two groups of patients. PMID- 7989878 TI - The epidemiology of male adolescent low back pain in a north suburban population of Melbourne, Australia. AB - OBJECTIVE: To determine the prevalence of low back pain (LBP) in an Australian metropolitan, male adolescent population. DESIGN: Self-reported, pretested questionnaire that included a definition of LBP and a description of the body area it affects. SETTING: Three government operated secondary schools in a growth corridor of north suburban Melbourne, Australia. SUBJECTS: Six hundred ten males attending secondary (high) school, aged between 12 and 19 yr. INTERVENTION: None. MAIN OBSERVATIONS: The point prevalence of LBP was found to be 16.7% and the sample prevalence 57%. The typical sufferer of adolescent LBP (ALBP) reported chronic LBP experienced up to a few days at a time, several times a month. CONCLUSIONS: The high prevalence of ALBP found by studies in other populations is confirmed in Australia. There is a clear need for further study of the etiology and potential preventative factors of ALBP, and for consideration of whether nontraumatic occupational LBP results more from an aggravation of a preexisting (adolescent) condition than from an unsafe or unsuitable work environment. PMID- 7989879 TI - The efficacy of cervical extension-compression traction combined with diversified manipulation and drop table adjustments in the rehabilitation of cervical lordosis: a pilot study. AB - OBJECTIVE: To experimentally investigate the effect of cervical extension compression traction combined with diversified chiropractic manipulation and drop table adjusting in establishing or increasing cervical lordosis. DESIGN: Blinded, before and after trial with pre- and postlateral cervical radiographic measurement. SETTING: Primary care private chiropractic clinic in Saugus, MA. SUBJECTS: A) Control group--convenience sample who had no health care for 10-14 wk, 30 persons. B) Treatment group 1, nonrandomized control trial, 35 persons, whose pre- and postlateral cervical radiographs were taken 10-14 wk apart and whose radiographs clearly depicted C1 through C7. C) Treatment group 2, nonrandomized control trial, 30 persons, whose pre- and postlateral cervical radiographs were taken 10-14 wk apart and whose radiographs clearly depicted C1 through C7. INTERVENTIONS: Treatment group 1: diversified spinal manipulation, drop table adjustments and cervical extension-compression traction five times per week for 10-14 wk (12 wk +/- 2). Treatment group 2: diversified spinal manipulation and drop table adjustments five times per week for 10-14 wk (12 wk +/- 2). MAIN OUTCOME MEASURES: Anterior head translation millimeters, C2 to C7 absolute rotation angle, angle of C1 to horizontal (atlas plane angle), five relative rotation angles (C2-3, C3-4, C4-5, C5-6, C6-7) and qualitative classification of lordotic configuration. RESULTS: No statistically significant changes existed between the pre- and posttests for the control group except in the C6-7 relative rotation angle. In the treatment group 1, statistically significant differences were found in all X-ray markings. Twenty-nine of 35 members have a lordosis after treatment compared to 11 of 35 before treatment. The C2 to C7 angle changed an average 13.2 degrees, C1 to horizontal changed an average 9.8 degrees, the anterior head translation reduced an average of 6.8 mm, the average relative rotation angle changed: C2-3: 3.1, C3-4: 5.5, C4-5: 4.80, C5 6: 2.7 and C6-7: 1.1. In the treatment group 2, no statistically significant changes existed between the pre- and posttests except atlas angulation to horizontal which increased an average of 3.0 degrees. CONCLUSIONS: A transformation to a lordotic configuration or increase in lordotic configuration occurred and was measured in the majority of treatment group 1 subjects, while no change in the control group and essentially no change in treatment group 2 was measured. Extension-compression traction combined with diversified chiropractic manipulation and drop table adjusting procedures may improve or partially reestablish the cervical lordosis in 10-14 wk of daily care. PMID- 7989880 TI - Nocturnal enuresis: treatment implications for the chiropractor. AB - OBJECTIVE: A comprehensive review of the literature concerning the etiology, diagnosis, and the natural history of primary nocturnal enuresis is presented. Contemporary treatment options are discussed in light of the documented annual remission rate of this disorder. DATA SOURCE: Articles reviewed were obtained by conducting a computer-aided search of papers indexed in Medline and the Index to Chiropractic Literature from 1989 to 1993. In addition, the Chiropractic Research Abstracts Collection and bibliographies from pertinent articles were manually searched. DATA SYNTHESIS: Primary nocturnal enuresis affects some 200,000 children and their families throughout Canada. Twenty percent of children wet the bed at age 5, 10% at age 10, and only about 1% at age 15. The documented natural history of the disorder reveals that for those affected, 10% to 20% exhibit spontaneous resolution per year. Contemporary treatment options center on three factors that play primary roles in the etiology of this condition: functional bladder capacity, patient conditioning and the circadian rhythm of nocturnal ADH secretion. CONCLUSIONS: The success of each therapeutic option must, in part, be attributed to the natural history of enuresis, as well as any educational or placebo aspects of treatment. Conditioning therapy utilizing the urine pad alarm may be the most reasonable initial mode of intervention. Spinal manipulative therapy has been shown to possess an efficacy comparable to the natural history. PMID- 7989881 TI - Conservative treatment of torn medial meniscus via mechanical force, manually assisted short lever chiropractic adjusting procedures. AB - OBJECTIVE: To present the first reported case of successful chiropractic intervention in treatment of a torn medial meniscus of the knee, the meniscal tear being documented by magnetic resonance imaging (MRI). CLINICAL FEATURES: A 54-yr-old woman complaining of right knee pain of several months' duration with accompanying marked functional impairment was diagnosed as having a tear in the posterior horn of the ipsilateral medial meniscus, verified by MRI studies of the same. Independent consultation with three medical specialists resulted in the unanimous decision that surgical intervention for the purpose of meniscectomy provided the only therapeutic approach indicated for the problem. However, the patient was reticent to undergo said surgical procedure and chose, instead, to utilize chiropractic care and conservative management in an effort to resolve her condition without having to resort to surgery. INTERVENTION AND OUTCOME: The patient received chiropractic treatment to the knee via mechanical force, manually assisted short lever chiropractic adjusting procedures (MFMA) utilizing an Activator Adjusting Instrument. Auxiliary treatment included the use of homeopathic therapy as an adjunct to chiropractic care. Said treatment resulted in a complete resolution of the patient's disability, the patient recovering full function of the knee joint and achieving an asymptomatic status without having to submit to surgical intervention and its possible adverse sequelae. CONCLUSIONS: Conservative management of meniscal tears via chiropractic treatment may provide a therapeutically effective and financially cost containing alternative to routine meniscectomy in certain cases involving torn medial menisci of the knee. PMID- 7989882 TI - Pelvic insufficiency fracture simulating metastatic bone disease. AB - OBJECTIVE: To present a rare case of pelvic insufficiency fracture mistaken for metastatic bone disease. CLINICAL FEATURES: A 58-yr-old female received 3 wk of chiropractic treatment for mechanical low back pain. The treatment offered no relief. Two months later, a bone scan revealed increased uptake in the pelvis, suggesting metastatic bone disease. A CT scan demonstrated several pubic fractures. Subsequent biopsy failed to show evidence of malignancy. A diagnosis of insufficiency fractures secondary to osteoporosis was made. INTERVENTION AND OUTCOME: She was referred to a rehabilitation clinic for physiotherapy and medication. She consulted a rheumatologist and was prescribed calcitonin. Ten months later, she was improved and the fractures had united. CONCLUSION: The absence of trauma frequently delays the diagnosis of parasymphyseal insufficiency fracture. The ambiguous X-ray features often lead to a diagnosis of metastatic bone disease. Early detection is important as significant morbidity may result from delaying the treatment. PMID- 7989883 TI - The use of the standardized patients in chiropractic education. PMID- 7989884 TI - Reactivity of leg alignment to articular pressure testing evaluation of a diagnostic test using a randomized crossover clinical trial approach. PMID- 7989885 TI - On political posturing and Hammurabi's medical legacy: two scenarios of health care reform. PMID- 7989886 TI - Primary care: poised to survive the chaos of managed care. PMID- 7989887 TI - A pediatrician's view of reform. PMID- 7989888 TI - In the shadow of power. PMID- 7989889 TI - The primary care specialties. PMID- 7989890 TI - Women, Ob-gyns and primary care: an essential relationship. PMID- 7989891 TI - Primary care view from the epicenter of managed care: Orange County, Ca. PMID- 7989892 TI - The primary care group model. PMID- 7989893 TI - The Morgan Health Group--an alternative for independent primary care physicians. PMID- 7989894 TI - New directions for the Joint Commission. Inside and outside the hospital. PMID- 7989895 TI - Steroids and peptic ulcer: an end to the controversy? PMID- 7989896 TI - Homocyst(e)ine and arterial occlusive diseases. AB - Homocysteine is a thiol-containing amino acid resulting from demethylation of methionine. The free and protein-bound forms of the amino acid and derived disulfides are called homocyst(e)ine [H(e)]. Multiple studies have shown elevated H(e) levels in patients with coronary, cerebrovascular, or peripheral arterial diseases; this association is frequent and independent of most other risk factors for atherosclerosis. In the 1993 Frontiers in Medicine Symposium investigators discussed the genetic, physiological, nutritional, and pharmacological mechanisms involved in the regulation of plasma H(e), the association of H(e) with arterial occlusive diseases, and the relationships of H(e) with nitric oxide and haemostasis. High plasma H(e) levels usually can be reversed with vitamin supplements. Whether vitamin supplements will affect the evolution of arterial occlusive diseases needs to be established in prospective, placebo-controlled, randomized, clinical trials. PMID- 7989897 TI - Corticosteroids and peptic ulcer: meta-analysis of adverse events during steroid therapy. AB - OBJECTIVES: This meta-analysis was performed to determine whether corticosteroid therapy induces the development of peptic ulcer and other putative complications of steroid therapy. DESIGN: A retrospective investigation in which we analysed all the randomized, double-blind, controlled trials (RDBCT) in which steroids had been administered that we were able to identify. The number of episodes of peptic ulcer, dermatological effects, sepsis, diabetes, hypertension, osteoporosis, psychosis and tuberculosis reported in both the placebo and steroid groups were compared. SETTING: The international medical literature was analysed for any RDBCT in which any steroid or ACTH had been administered in any dosage for any duration, and any putative complication of steroid therapy was reported. SUBJECTS: Of 1857 articles, 93 satisfied our requirements and were analysed by the meta-analytic techniques of Peto, DerSimonian and Laird. A total of 6602 patients were included. MAIN OUTCOME MEASURES: The relative frequencies of each of these eight 'complications' were compared in the placebo and steroid groups using conventional statistics and meta-analysis. The relative frequencies of 'annualized' subgroups of patients who received treatment for 1 to 7 days, 1 week to 1 month, 1 to 3 months and more than 3 months, were similarly analysed. RESULTS: Nine of 3267 patients in the placebo group (0.3%) and 13 of 3335 patients in the steroid group (0.4%) were reported to develop peptic ulcer (P > 0.05). The dermatological cosmetic effects of steroid therapy were observed more frequently in the steroid group (P < 0.001), as was diabetes (P < 0.001), hypertension (P < 0.01) and psychosis (P < 0.001). Sepsis, osteoporosis and tuberculosis all occurred more frequently in the steroid than in the placebo group, but the differences are not statistically significant. CONCLUSIONS: Peptic ulcer is a rare complication of corticosteroid therapy that should not be considered a contraindication when steroid therapy is indicated. PMID- 7989899 TI - Prognosis in therapy-resistant hypertension. AB - OBJECTIVES: To study the prognosis in therapy-resistant hypertension (RH). DESIGN: Patients with RH and age- and sex-matched responding hypertensives, were followed-up for a period of 7 years. SETTING: All subjects were outpatients at a secondary referral centre for hypertension. SUBJECTS: (i) Age < or = 65 years; (ii) no prior diagnosis of secondary hypertension; (iii) on antihypertensive triple-drug therapy of optimal dosage; (iv) diastolic blood pressure remaining 5 mmHg above their (age-related) target pressure; (v) no history of renal failure, heart failure, stroke or myocardial infarction; and (vi) no record of noncompliance. A total of 800 patients were screened. Thirty-six were finally included. For each study patient, two control patients were randomly selected. INTERVENTIONS: Continuous efforts to optimize blood pressure control were made in all patients. MAIN OUTCOME MEASURES: Transient ischaemic attack or stroke, myocardial infarction, congestive heart failure, renal failure, and death. Development of non-insulin-dependent diabetes mellitus (NIDDM). RESULTS: At the end of the follow-up period, RH had a casual functional blood pressure 2/6 mmHg higher than the control hypertensives. RH exhibited an increased incidence of stroke (P < 0.05), renal insufficiency (P < 0.05) and NIDDM (P < 0.05). RH patients had an increased risk of suffering an event during the 7 years [odds ratio (OR) 2.71; P < 0.05]. CONCLUSIONS: Resistance to antihypertensive therapy may persist even when therapy is aggressively applied in compliant patients. RH is associated to an increased risk of stroke and of target organ damage, foremost renal insufficiency. The apparent association between RH, obesity and NIDDM may imply that hyperinsulinaemia is involved in therapy resistance. PMID- 7989898 TI - Homocysteine and cysteine: determinants of plasma levels in middle-aged and elderly subjects. AB - OBJECTIVES: Hyperhomocysteinaemia is an independent risk factor for cardiovascular disease. We explored possible determinants of plasma homocysteine and cysteine concentrations amongst middle-aged and elderly subjects. DESIGN AND SUBJECTS: Of 501 35-95-year-old randomly selected residents of Lund and Malmo, Sweden, 244 (49%; 131 men, 113 women) were investigated. RESULTS: Total plasma homocysteine concentrations were higher in men than in women (mean +/- SD: 13.9 +/- 4.1 and 12.3 +/- 4.1 mumol L-1; P < 0.001), increased markedly with age (Spearman's rho = 0.488; P < 0.001), and were correlated (P < 0.001) to concentrations of blood folate, serum vitamin B12, and serum creatine (rho = 0.366, -0.338, and 0.463). Users of multivitamins had lower homocysteine levels than nonusers [10.5 +/- 3.3 mumol L-1 (n = 31) and 13.5 +/- 4.2 mumol L-1 (n = 213), respectively; P < 0.001]. Total plasma cysteine concentrations also increased significantly with age and increasing serum creatinine, but were unrelated to gender, blood folate, serum vitamin B12 and use of multivitamins. CONCLUSIONS: Age, gender, folate, serum vitamin B12, serum creatinine and multivitamin usage are all important determinants of the plasma homocysteine concentration, whereas only age and serum creatinine are determinants of the plasma cysteine concentration. The age-related increase in homocysteine and cysteine may be linked to the age-related impairment of renal function, whereas the sex difference in plasma homocysteine may be because of the fact that more homocysteine is formed in men than in women in conjunction with creatine creatinine synthesis. PMID- 7989900 TI - The efficacy of multiple risk factor intervention in treated hypertensive men during long-term follow up. Risk Factor Intervention Study Group. AB - OBJECTIVE: To examine the feasibility and efficacy of a multifactorial intervention programme directed towards hypercholesterolaemia, smoking, and diabetes mellitus in treated hypertensive patients after more than 3 years' follow-up and to describe the incidence of cardiovascular complications. DESIGN: Open, randomized, parallel-group study with allocation either to a comprehensive multiple risk factor modification programme or to usual care. SETTING: Outpatient clinic in a city hospital. PATIENTS: A total of 508 male patients with treated hypertension, aged 50-72 years, with at least one of the following: serum cholesterol > or = 6.5 mmol L-1, smoking or diabetes mellitus. INTERVENTION: Individually given advice and group meetings based on nutritional advice and behavioral treatment principles. Drug therapy could be instituted to achieve the treatment goals in the intervention group: serum total cholesterol below 6.0 mmol L-1, no smoking, and HbA1c below 6.0%. Diastolic blood pressure below 90 mmHg was the treatment goal in both groups. MAIN OUTCOME MEASUREMENTS: Serum cholesterol, HbA1c, diastolic blood pressure, smoking. Cardiovascular end-points were recorded. RESULTS: The net changes were (change intervention--change usual care): serum cholesterol -5.0% (95% confidence interval, -7.6 to -2.3%), 17.6% more stopped smoking (P = 0.04); diastolic blood pressure and HbA1c remained unchanged. The incidence of stroke was lower in the intervention group compared with the usual-care group: 2.0 and 6.7%, respectively (P = 0.017). CONCLUSION: The intervention programme was comparatively successful with regards to the effects on hypercholesterolaemia and smoking habits. An unexpected decrease in the stroke incidence was observed in the intervention group compared with the usual-care group. PMID- 7989901 TI - The occurrence of polyglandular autoimmune syndrome type III associated with coeliac disease in patients with sarcoidosis. AB - OBJECTIVES: To study whether an association between polyglandular autoimmune (PGA) syndrome type III [including autoimmune thyroid disease (ATD) and insulin dependent diabetes mellitus (IDDM)], coeliac disease and sarcoidosis, exists. DESIGN: In patients with documented sarcoidosis, the presence of the disease constellation of ATD, IDDM and coeliac disease was examined. SETTING: The patients were recruited at the Department of Pulmonary Medicine, and the study was conducted at the Department of Endocrinology, Lund University Clinics, General Hospital, Malmo, Sweden. SUBJECTS: Of all patients (n = 89) with documented sarcoidosis attending the Department of Pulmonary Medicine between January 1980 and December 1991, 78 patients (44 males, 34 females: median age at the time of the study 48 years, range 22-81 years: median observation time since the diagnosis of sarcoidosis 120 months, range 1-468 months) were examined in the present study. RESULTS: Amongst the 78 patients with documented sarcoidosis, one female patient was found with PGA syndrome type III, coeliac disease and sarcoidosis. CONCLUSIONS: This present patient further indicates the existence of an association between polyglandular autoimmune (PGA) syndrome type III, coeliac disease and sarcoidosis. To determine whether this disease constellation might constitute a new syndrome, further studies on larger groups of patients with sarcoidosis are demanded. PMID- 7989902 TI - Pressure-dependent, enhanced natriuretic response to low-dose, atrial natriuretic peptide infusion in essential hypertension. AB - OBJECTIVE: To examine whether the effect of atrial natriuretic peptide (ANP) on renal glomerular and tubular segmental handling of sodium in patients with essential hypertension is pressure dependent. DESIGN: Part 1. The renal effects of a low-dose continuous infusion (10 ng kg-1 min-1) with ANP for 1 h were compared in 10 untreated essential hypertensives (EH) and 13 normotensive control subjects (CS). Part 2. The hypertensives were studied on another day with ANP infusion during preceding acute BP reduction with sodium nitroprusside infusion (NP). The results were compared with those obtained during infusion with ANP+placebo (Part 1). METHODS: Lithium clearance was used to estimate the proximal tubular reabsorption of sodium. RESULTS: Part 1. Atrial natriuretic peptide caused an exaggerated increase in urinary sodium excretion (+102 vs. +38%: P < 0.05), fractional excretion of sodium (+80 vs. +37%: P < 0.05), and urinary output (+56 vs. +8.3%; P < 0.05) in EH compared with CS. Glomerular filtration rate and filtration fraction increased to the same degree in both groups. Absolute lithium clearance (CLi) increased and FELi tended to increase (P = 0.061) in EH, but these were unchanged in CS. The increase in plasma cyclic guanosine 5'-phosphate (cGMP) and urinary excretion of cGMP and the decrease in plasma aldosterone during ANP infusion were the same in the two groups. Part 2. During NP infusion the natriuresis caused by ANP in EH was reduced (+51 vs. +99%; P < 0.05). The relative changes in GFR, CLi, and FELi during ANP infusion were not affected by the preceding BP reduction with NP. Mean arterial pressure was reduced from 122 to 101 mmHg during NP infusion. The relative increase in sodium excretion in EH was significantly correlated to mean arterial pressure. CONCLUSIONS: Low-dose ANP infusion causes an exaggerated natriuresis in untreated essential hypertensives due to a more pronounced reduction in tubular reabsorption. After BP reduction, the natriuresis induced by ANP in essential hypertensives is decreased, probably due to a less pronounced reduction in tubular reabsorption beyond the proximal tubules. We suggest that the enhanced natriuretic response to ANP in EH in secondary in some degree to the elevated systemic pressure. PMID- 7989903 TI - Incidence of pheochromocytoma in South Galicia, Spain. AB - OBJECTIVES: To estimate the incidence of pheochromocytoma in the population of South Galicia (Spain) during the period 1980-1992. DESIGN: A prospective study. SETTING: The General Hospital of Vigo, a tertiary referral centre. SUBJECTS: New cases of pheochromocytoma diagnosed in the population during the years 1980-1992. The average population size was 523,934 inhabitants, (52% female, 48% male). MAIN OUTCOME MEASURES: All data were obtained from the Medical Registry, which ensures virtually complete case ascertainment for diagnosed pheochromocytoma in the population. All cases were histologically confirmed. The average annual incidence rate of pheochromocytoma was calculated. RESULTS: For the study period, 14 new cases (eight female and six male) of pheochromocytoma were diagnosed in the population of South Galicia. The average annual incidence rate in the population was 2.06 (range 0.0-3.93) per million. This incidence rate was significantly higher in the female population (2.26 vs. 1.84; P < 0.05). The mean age at diagnosis was 43 +/- 12 (range 21-65) years. Thirteen of the 14 cases were diagnosed in living patients (two discovered incidentally at operation) and one case was diagnosed at autopsy. One pheochromocytoma was located outside the adrenals. All but one tumour were benign. One patient had pheochromocytoma as part of the multiple endocrine neoplasia type IIa, and in four patients it was associated with neurofibromatosis (28.57%). Four of the 13 patients surgically treated had residual hypertension. CONCLUSIONS: The incidence of pheochromocytoma in our population is similar to that reported from other European countries. Routine screening for this disease is not recommended, but postoperative follow up of the patients is needed. A wider study is necessary to confirm the high association with neurofibromatosis in our population. PMID- 7989904 TI - Systemic polyarteritis nodosa as the initial manifestation of a gastric adenocarcinoma. AB - We report a case of systemic polyarteritis nodosa (PAN) leading to the discovery of an as yet asymptomatic, surgically curable gastric adenocarcinoma. PAN is rarely associated with malignancies and in such cases these are more often malignant haematological diseases than solid neoplasms. The immunopathological findings, the temporal relationship between both conditions, and the spontaneous resolution of vasculitis after tumour removal suggest a paraneoplastic origin of the systemic angitis. PMID- 7989905 TI - Factitious disorder presenting with acute cardiovascular symptoms. AB - A 23-year-old female student exhibited all the characteristics of chronic factitious disorder with physical symptoms (Munchhausen's syndrome): deliberate simulation of illness, peregrination, fantastic pseudology and dramatic circumstances on admittance. The patient induced impressive blood pressure peaks by the Valsalva manoeuvre. She also simulated arrhythmias, seizures and unconsciousness. Her symptoms had previously led to comprehensive cardiological, neurological and endocrinological evaluations and treatment in at least three different countries in two continents. A literature survey suggests that facitious cardiovascular symptoms have become more frequent during recent decades. PMID- 7989906 TI - Evaluation of latex D-dimer tests. PMID- 7989907 TI - Prevention with glucocorticoids of extrapancreatic tumour-hypoglycaemia as a result of increased 'big' insulin-like growth factor II. PMID- 7989908 TI - Reactivated movement of decondensed rat sperm models and a description of their ultrastructure. AB - This study aimed at finding optimal conditions to decondense rat sperm nuclear chromatin with minimal damage. This was judged by the ability of the sperm-tail axoneme in the partially decondensed sperm models to be reactivated. Decondensation was assessed by phase contrast microscopy. Partial decondensation was judged to occur when the bright refractive appearance of the sperm nucleus turned black, and full decondensation when the nucleus turned pale and increased in volume. Demembranation was shown to have occurred by electron microscopy. With 0.03% Triton X-100 rat caudal epididymal sperm were partially demembranated to produce sperm models. Demembranation using a 0.1% solution of Triton X-100 was complete, but as with the solution of 0.05% Triton X-100, resulted in poorer reactivation of the partially decondensed sperm models. Reactivated movement of decondensed sperm models was used to assess the effect of the decondensing agents DTT and heparin. We were only able to achieve reactivation of sperm models that had undergone partial decondensation. Optimal reactivation was obtained after rat sperm models had decondensed in the decondensation solution containing 5 mM DTT, 6 mM EDTA, and 27.3 or 34.1 USP/ml heparin. Concentrations of heparin above or below these values resulted in a decrease in the number of sperm models reactivated. Ultrastructurally, sperm partially decondensed with 5 mM DTT, 6 mM EDTA, and 34.1 USP/ml heparin had their plasma membrane further extracted compared with sperm treated with 0.03% Triton X-100 alone. Decondensation was greatest in the peripheral regions of the nucleus with extraction of the acrosome but not of the perforatorium. The decondensed regions had a filamentous appearance. This procedure will allow access to sperm nuclear chromatin for experimental manipulation in rat sperm models. PMID- 7989909 TI - Oocyte nuclear maturation at the time of oocyte aspiration is independent of in vitro fertilization potential in the domestic cat. AB - This study determined (1) the temporal kinetics of nuclear maturation at and after follicular oocyte aspiration and (2) the significance of variations in nuclear maturation and sperm-oocyte co-incubation interval on in vitro fertilization (IVF) in the domestic cat. Female cats were treated with pregnant mares' serum gonadotropin followed 84 h later with human chorionic gonadotropin (hCG). Twenty-five hours after hCG, ovarian follicular oocytes were aspirated laparoscopically and classified according to morphological criteria. Oocytes classified as mature were cultured for 0, 2, 4, 6, or 8 h in Ham's F10 medium and then stained for nuclear maturation. The proportion of oocytes at metaphase II was similar (P > 0.05) at 0 (38.2%) and 2 (48.5%) h of culture, but was higher (P < 0.05) at 4 (76.5%), 6 (82.8%), and 8 (92.3%) h. Oocytes also were collected and cultured as described above and then co-incubated for 2 or 18 h with 5 x 10(5) motile cat sperm cells/ml. The incidence of IVF (cleavage to 2-cells by 30 h post insemination) was consistently 2-fold higher (P > 0.05) for the 18 h compared to the 2 h gamete co-incubation groups. However, despite differences in nuclear maturation at the time of oocyte recovery, IVF success was unaffected (P > 0.05) by pre-insemination culture interval (0 h, 72.7%; 2 h, 73.3%; 4 h, 70.7%; 6 h, 57.8%; 8 h, 62.5%; 18 h group). Thus, the majority of oocytes recovered from cats treated with this gonadotropin regimen has not achieved metaphase II by follicular aspiration.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7989910 TI - Cell cycle remodeling requires cell-cell interactions in developing Xenopus embryos. AB - Flow cytometric analysis has revealed a general remodeling of the cell cycle in developing Xenopus embryos. During early gastrulation the cell cycle is dominated by S phase, with 82% of all interphase nuclei in the S phase fraction. As development proceeds over the next 60 hours, a gradual decline in S phase cells is proportional to an increase in the number of cells in G1. By the late tailbud stage, 85% of all nuclei are found in the G1 fraction, approximating the cell cycle profile of adult somatic cells. Cell cycle remodeling occurs on schedule even in embryos that have been dissociated into a loose mound of cells which remain in close proximity to one another. However, cells that have been widely separated by manual dispersion do not undergo remodeling. These dispersed cells maintain an S phase-dominated cell cycle and continue to show patterns of blastula and gastrula gene expression at least 30 hours beyond gastrulation. We conclude that cell cycle remodeling occurs in the absence of an intact embryo but requires the inductive influences associated with a community of cells. PMID- 7989911 TI - Posttraumatic stress disorder among Vietnam Theater Veterans. A causal model of etiology in a community sample. AB - Data from the National Vietnam Veterans Readjustment Study, conducted from 1986 to 1988, were used to develop and cross-validate a model of the etiology of posttraumatic stress disorder (PTSD) among a community sample of 1198 male Vietnam theater veterans. The initial model specified causal paths among five sets of variables, ordered according to their historical occurrence: a) premilitary risk factors and traumas, b) war-related and non-war-related traumas during the military, c) homecoming reception, d) postmilitary traumas, and e) PTSD. The initial model was refined and then cross-validated, leading to the specification of a final model with highly satisfactory fit and parsimony. In terms of the magnitude of their contribution to the development of PTSD, lack of support from family and friends at the time of the homecoming and exposure to combat were the two most influential contributors. Other contributing factors, in order of importance, were Hispanic ethnicity, societal rejection at the time of homecoming, childhood abuse, participation in abusive violence, and family instability. Exposure to war-related and non-war-related traumas occurred largely independently of each other, with war-related traumas contributing substantially more than non-war-related traumas to the development of PTSD. Limitations to interpretation of the results are noted due to the retrospective nature of the data and the inevitable omission of other etiological factors. PMID- 7989912 TI - Utilization of mental health services by minority veterans of the Vietnam era. AB - This study sought to identify differences in utilization of mental health services among members of five minority groups who served in the military during the Vietnam era. Data on utilization of mental health services from five different types of provider (Veterans Affairs [VA] and non-VA mental health providers, nonpsychiatrist physicians, clergy, and self-help groups) were obtained from a national survey of Vietnam era veterans (the National Vietnam Veterans Readjustment Study) along with information on sociodemographic characteristics, health status, income, and health insurance coverage. Chi-square tests and multivariate logistic regression analyses were used to compare use of various services among whites, blacks, Puerto Rican Hispanics, Mexican Hispanics, and others. Black veterans and Mexican Hispanic veterans were significantly less likely than white veterans to have used non-VA mental health services or self help groups, after adjusting for health status and other factors. There were no differences between ethnocultural groups in use of VA mental health services, or services provided by nonpsychiatrist physicians or clergy, even after adjustment was made for health and economic factors. Although military service during the Vietnam conflict may have alienated many minority veterans from the federal government, the reluctance of minorities to use non-VA mental health services does not extend to the VA system. Further studies are needed to clarify the reasons for less non-VA service use among some minority groups. PMID- 7989913 TI - Molecular psychiatry. Adaptations of receptor-coupled signal transduction pathways underlying stress- and drug-induced neural plasticity. AB - Advances in molecular biology and neuroscience are leading to new opportunities for elucidation of the pathophysiology of psychiatric disorders and the long-term actions of psychotropic drugs. The actions of first messengers, including neurotransmitters, neuropeptides, and neurotrophins, on neuronal function can now be viewed in terms of their regulation of complex intracellular signal transduction pathways. These pathways mediate most actions of first messengers, including fast mediatory (e.g., cell firing), short-term modulatory (e.g., neuronal metabolism, receptor sensitivity, neurotransmitter sensitivity), and long-term modulatory (e.g., gene expression). Moreover, it is becoming increasingly evident that adaptations of receptor-coupled intracellular pathways, referred to here as neural plasticity, mediate the long-term actions of psychotropic drug treatments. In addition, an inability to mount the appropriate adaptive responses to environmental stressors could contribute to the pathophysiology of psychiatric disorders. The following provides a brief overview of receptor-coupled intracellular signal transduction pathways in brain and general mechanisms of neural plasticity. Specific examples of neural plasticity in response to stress, antidepressant treatments, and drugs of abuse are discussed in greater detail. Continued elucidation of the intracellular signal transduction pathways which govern neuronal function and the mechanisms that mediate neural plasticity will provide the basis for the development of more effective and fast-acting therapeutic agents, as well as identification of the abnormalities underlying psychiatric disorders. PMID- 7989914 TI - Psychopathology and cognitive decline in dementia. AB - This study investigated the correlation between the degree and quality of cognitive impairment and the presence and degree of severity of psychopathology. Sixty-four demented outpatients were rated for cognition by the Mental Status Questionnaire and for psychopathology by the BEHAVE-AD Reisberg questionnaire. A statistical analysis of the correlations between the cognitive and psychopathological parameters was performed. The study indicated a high rate of psychopathology (as high as 83% of the patients). No significant correlation was found between the cognitive grading score and the presence of psychopathology, except in the space of declined spatial orientation and the occurrence of hallucinations. Psychopathology is a common phenomenon occurring in the course of dementia in the form of Alzheimer's disease or multi-infarct dementia. There is a certain increase in the degree of psychopathology that correlated with cognitive impairment. The high correlation between impaired spatial orientation and the presence of hallucinations seems to point to a common neuropathological substrate. PMID- 7989915 TI - A longitudinal study of substance use and community violence in schizophrenia. AB - The authors report the findings of a longitudinal study testing the hypothesis that substance use leads to subsequent violence in the community. Subjects were 103 patients with a Structured Clinical Interview for DSM-III-R diagnosis of schizophrenia or schizoaffective disorder who were seen in an outpatient clinic for the treatment of schizophrenia. Data on substance use and violent behavior were collected by review of medical records. Results indicated that use of drugs and alcohol was associated with increased odds of concurrent and future violent behavior when compared with persons with schizophrenia and no substance use. Odds of violence were particularly elevated for individuals having a pattern of polysubstance use involving illicit substances. PMID- 7989916 TI - Factors influencing adjustment of high school students in an international exchange program. AB - The present study aims to investigate which psychosocial factors measured before departure are predictive of various aspects of intercultural adjustment among Japanese teenagers enrolled in a foreign exchange student program. A cohort of 188 Japanese high school students, who had been selected to spend 1 year in various countries of the world under the aegis of an international exchange student program, was administered the Maudsley Personality Inventory, the Parental Bonding Instrument, the General Health Questionnaire and the People in Your Life Scale before their departure from Japan. Six months after arrival in the host community, they were again asked to complete the General Health Questionnaire and relevant sections of the People in Your Life Scale. The students showed highly significant and substantial deterioration in all three areas of psychosocial adjustment: they reported more psychiatric symptoms, less availability of social relationships, and less satisfaction with them in their host community than at home. Psychiatric symptoms were best predicted by perceived adequacy of intimate attachments and neuroticism measured before departure, availability of social relationships abroad by availability and adequacy of social relationships and adequacy of attachments at home, and satisfaction with social relationships abroad by satisfaction with attachments at home and by paternal care before age 16. This study thus demonstrates that studying abroad entails deterioration in psychosocial adjustment of the adolescents studied and that different factors are influential in different aspects of adjustment. The importance of a prospective and multifaceted study of intercultural adjustment process is emphasized. PMID- 7989917 TI - Obsessive-compulsive disorder among patients entering substance abuse treatment. Prevalence and accuracy of diagnosis. AB - Patients (N = 217) admitted to two community-based substance abuse outpatient treatment programs participated in a structured clinical interview to determine the comorbidity of obsessive-compulsive disorder. Twenty-four patients (11.1%) met the diagnostic criteria for obsessive-compulsive disorder, which is significantly higher than the general population prevalence of this disorder. However, only eight of these patients were accurately diagnosed with this condition by their primary counselors. Clinical implications of these findings are discussed. PMID- 7989919 TI - Mother-son incest and its long-term consequences: a neglected phenomenon in psychiatric practice. PMID- 7989918 TI - Effectiveness of office-based psychiatric practice using a structured diagnostic interview to guide treatment. PMID- 7989920 TI - The positive teddy bear sign: transitional objects in the medical setting. PMID- 7989921 TI - Treatment of obsessive-compulsive symptoms in schizophrenia with a neuroleptic selective serotonin reuptake inhibitor combination: two case reports. PMID- 7989922 TI - Jauhar: mass suicide by self-immolation in Waco, Texas. PMID- 7989923 TI - International workshop on iron-sulfur proteins: new structures and unexpected functions. April 10-12, 1994, Konstanz, Germany. Abstracts. PMID- 7989924 TI - Myelodysplasia and acute myelogenous leukemia after myeloablative therapy with autologous stem-cell transplantation. PMID- 7989925 TI - The role of transplantation in non-Hodgkin's lymphoma. PMID- 7989927 TI - Myelodysplastic syndrome as a late complication following autologous bone marrow transplantation for non-Hodgkin's lymphoma. AB - PURPOSE: To determine the incidence, natural history, and risk factors associated with myelodysplastic syndrome (MDS) occurring as a late complication following autologous bone marrow transplantation for patients with non-Hodgkin's lymphoma. METHODS: We retrospectively reviewed the charts of all 262 patients who underwent autologous bone marrow transplantation for non-Hodgkin's lymphoma at the Dana Farber Cancer Institute from 1982 through 1991. Although patients received a variety of treatments before they were eligible for transplant, identical myeloablative therapy (cyclophosphamide 60 mg/kg/d for 2 days plus total-body irradiation twice daily for 3 days) was administered in each case. By collecting data on pretransplant and early posttransplant variables, we attempted to identify risk factors for the development of MDS. RESULTS: The crude overall incidence of posttransplant MDS or acute myeloid leukemia (AML) was 7.6%. The actuarial risk at 6 years was 18% +/- 9%. The median time of onset was 31 months (range, 10 to 101) after transplant or 69 months (range, 27 to 141) after initial treatment for lymphoma. Pretreatment variables predictive for the development of MDS (univariate analysis) included prolonged interval between initial treatment and the transplant procedure (P = .003), increased duration of exposure to chemotherapy (P = .019) or to alkylating agents (P = .045), and use of radiation therapy (P = .032) or pelvic radiation (P = .003) before transplant. CONCLUSION: MDS is a potential complication of autologous bone marrow transplantation for non Hodgkin's lymphoma; bone marrow stem-cell damage sustained before the transplant may be the most important risk factor. PMID- 7989926 TI - Incidence and characterization of secondary myelodysplastic syndrome and acute myelogenous leukemia following high-dose chemoradiotherapy and autologous stem cell transplantation for lymphoid malignancies. AB - PURPOSE: To analyze the risk of developing myelodysplastic syndrome (MDS) or acute myelogenous leukemia (AML) following autologous bone marrow transplantation (ABMT) or peripheral stem-cell transplantation (PSCT) and to determine the impact on failure-free survival (FFS). PATIENTS AND METHODS: Patients underwent ABMT or PSCT for the treatment of Hodgkin's disease (HD) and non-Hodgkin's lymphoma (NHL) at the University of Nebraska Medical Center. For those patients who went on to develop MDS/AML, controls were selected and a case-control-within-a-cohort study undertaken. RESULTS: Twelve patients developed MDS or AML a median of 44 months following ABMT/PSCT. The cumulative incidence (P = .42) and the conditional probability (P = .32) of MDS/AML were not statistically different between HD and NHL patients. Age greater than 40 years at the time of transplant (P = .05) and receipt of a total-body irradiation (TBI)-containing regimen (P = .06) were predictive for developing MDS/AML in patients with NHL. CONCLUSION: There is an increased risk of MDS/AML following ABMT/PSCT for lymphoid malignancies. NHL patients age > or = 40 years at the time of transplant and who received TBI are at greatest risk. PMID- 7989928 TI - Fractionated total-body irradiation, etoposide, and cyclophosphamide plus autografting in Hodgkin's disease and non-Hodgkin's lymphoma. AB - PURPOSE: High-dose etoposide was incorporated into a regimen of fractionated total-body irradiation (FTBI) and high-dose cyclophosphamide before autologous transplant with the goal to enhance the antitumor effect of the myeloablative regimen in poor-risk lymphoid malignancies. PATIENTS AND METHODS: Ninety-six patients, 24 with recurrent or refractory Hodgkin's disease and 72 with poor-risk non-Hodgkin's lymphoma (NHL), were treated on this study. Cytoreduction with conventional therapy was attempted before administration of the preparatory regimen. The preparatory regimen consisted of 12 Gy total-body irradiation administered in 10 1.2-Gy fractions on day -8 through day -5, etoposide 60 mg/kg on day -4, and cyclophosphamide 100 mg/kg on day -2. Patients with NHL received bone marrow purged with a panel of monoclonal antibodies and complement on day 0, while patients with Hodgkin's disease received peripheral-blood stem cells alone or with unmanipulated bone marrow. RESULTS: The major morbidities of transplant were mucositis and skin toxicity. Eight patients (8.6%) died of regimen-related toxicities within 100 days of transplant. Engraftment was related to the rescue product; the median time to a neutrophil count more than 500/microL was 10 days for patients with Hodgkin's disease and 16 days for NHL patients. With a maximum follow-up duration of longer than 5 years, the 3-year actuarial survival rate is 57%. At 3 years, the actuarial freedom from progression (FFP) rate is 55% and the event-free survival rate is 47% for patients with Hodgkin's disease, while the respective figures for NHL patients are 60% and 53%. Among 32 patients with intermediate- and high-grade lymphoma transplanted subsequent to first relapse, 70% are free of lymphoma and 60% are event-free at > or = 3 years. CONCLUSION: The preparatory regimen consisting of FTBI, etoposide, and cyclophosphamide demonstrates relative efficacy in patients with Hodgkin's disease and NHL selected for high-dose therapy. Longer follow-up duration is needed to determine the rate of cure and to assess late complications. Major remaining challenges for high-dose therapy are a more inclusive strategy for all poor-risk patients and the need to reduce posttransplant relapses. PMID- 7989929 TI - High-dose fractionated total-body irradiation, etoposide, and cyclophosphamide followed by autologous stem-cell support in patients with malignant lymphoma. AB - PURPOSE: To evaluate a high-dose treatment regimen of fractionated total-body irradiation (TBI), etoposide, and cyclophosphamide (Cy) followed by autologous stem-cell transplantation (ASCT) in patients with malignant lymphoma. PATIENTS AND METHODS: Fifty-three patients with non-Hodgkin's lymphoma (NHL; n = 43) or Hodgkin's disease (HD; n = 10) received 12.0 Gy of fractionated TBI, etoposide 60 mg/kg, and Cy 100 mg/kg followed by infusion of autologous hematopoietic stem cells. RESULTS: Thirty-one of 53 patients are alive a median of 643 (range, 177 to 1,144) days after transplant. The 2 year Kaplan-Meier (K-M) estimates of survival, event-free survival (EFS), and relapse for all 53 patients were 54%, 45%, and 43%, respectively. Sixteen of 24 patients with less advanced disease and 10 of 29 patients with more advanced disease survive free of disease for K-M estimates of EFS of 61% and 31%, respectively (P = .006). The K-M estimates of relapse were 34% for patients with less advanced disease and 53% (P = .05) for patients with more advanced disease. The K-M estimates of dying from causes other than relapse were 8% in patients with less versus 25% in patients with more advanced disease (P = .09). CONCLUSION: These data indicate that approximately 60% of patients transplanted early after failure of initial therapy for malignant lymphoma are projected to be disease-free more than 2 years after treatment with fractionated TBI, etoposide, and Cy and infusion of autologous hematopoietic stem cells. The transplant-related mortality rate is low and relapse is the main cause of treatment failure in patients with less advanced disease. For patients with more advanced disease, the K-M estimates of both transplant-related deaths (25%) and relapse (53%) remain major problems. PMID- 7989930 TI - Improved survival in patients with limited stage IIIA Hodgkin's disease treated with combined radiation therapy and chemotherapy. AB - PURPOSE: Patients with laparotomy-staged (PS) III 1A Hodgkin's disease confined to the upper abdomen are believed to have a favorable prognosis and require less aggressive treatment than patients with more-extensive stage III disease. We evaluated prognostic factors and outcome in 93 patients with PS III 1A Hodgkin's disease treated either with radiation therapy (RT) alone or combined RT and chemotherapy (combined modality treatment [CMT]) to determine the extent of treatment needed in this subgroup of stage IIIA patients. MATERIALS AND METHODS: We retrospectively reviewed the freedom from relapse (FFR) rate, sites of recurrence, and survival rate of PS III 1A patients selected to receive extended field irradiation (MPA, n = 27), total-nodal irradiation (TNI, n = 34), and CMT (n = 32) between 1969 and 1987. CMT consisted of six cycles of mechlorethamine, vincristine, procarbazine, and prednisone (MOPP) chemotherapy and MPA. Patients treated with MPA were part of a prospective trial designed to reduce treatment to patients with minimal stage III disease with very favorable characteristics. RESULTS: Histologic subclass and treatment were the only prognostic factors for FFR and survival rates. Patients with nodular sclerosis or lymphocyte predominance histology had significantly higher FFR and survival rates compared to patients with mixed-cellularity (MC) histology. The 10-year actuarial FFR of PSIII 1A patients treated with MPA was only 39%, versus 55% for TNI (P = .02) and 94% for CMT (v MPA, P < .0001; v TNI, P = .006). The patterns of recurrence in patients who received MPA and TNI were significantly different, with MPA patients relapsing more often in untreated pelvic or inguinal nodes, and TNI patients relapsing more often in extranodal sites with or without nodal sites. The 10-year actuarial overall survival rate for patients treated with CMT was 89% versus 78% for MPA (v CMT, P = .09) and 70% for TNI (v CMT, P = .05). CONCLUSION: Patients with PSIII 1A Hodgkin's disease treated with RT have a significantly higher risk of relapse and potentially a poorer survival compared with patients treated with CMT. These findings suggest that CMT should play a greater role in the treatment of this favorable substage of patients. Management with modified chemotherapy and RT in an attempt to reduce long-term treatment-induced complications may be a preferred approach for future trials. PMID- 7989931 TI - Intravascular lymphomatosis: a clinicopathologic study of 10 cases and assessment of response to chemotherapy. AB - PURPOSE: We report a clinicopathologic study of 10 cases of intravascular lymphomatosis (IVL) seen at a single institution, and assess the response to chemotherapy in these patients, as well as those collected from a literature review. PATIENTS AND METHODS: The clinical, pathologic, and immunophenotypic features of 10 cases of IVL diagnosed at the Johns Hopkins Hospital since 1977 were studied. Follow-up information was obtained in each case by consultation with the treating physician. In addition, cases of IVL reported previously in which patients were treated with chemotherapy and for which follow-up data were available at the time of publication were reviewed. RESULTS: In the present series of 10 cases, the most common clinical features were fever of unknown origin (FUO), mental status changes, and rash. Diagnostic specimens were obtained from a variety of sources, including brain, skin, prostate, liver, kidney, and gallbladder. All of the four patients treated with combination chemotherapy are alive and two have achieved long-term survival (48 and 45 months, respectively); the remaining two are alive and in complete remission (CR) after short follow-up duration of 6 months. Among 35 patients reported in the literature who received chemotherapy (including four from this series), 43% attained a CR and were free of disease at the time of publication. None of the three patients in our series who received localized therapy (surgery with or without radiation therapy) is alive (mean survival duration, 9 months). For the three patients diagnosed at postmortem examination, the mean interval between onset of symptoms and death was 3 months, and disease was widespread. CONCLUSION: These findings suggest that IVL represents a high-grade non-Hodgkin's lymphoma (NHL) with a propensity for systemic dissemination, and that CR and long-term survival may result in patients treated with aggressive combination chemotherapy. PMID- 7989932 TI - Allogeneic bone marrow transplantation in adult acute lymphoblastic leukemia in first complete remission: a comparative study. French Group of Therapy of Adult Acute Lymphoblastic Leukemia. AB - PURPOSE: Optimal postremission therapy remains controversial in adult patients with acute lymphoblastic leukemia (ALL). In a large multicentric trial (LALA87), we compared allogeneic bone marrow transplantation (BMT) with other postremission therapies (chemotherapy or autologous transplantation) using the result of the human leukocyte antigen (HLA) typing as a random allocation. PATIENTS AND METHODS: Patient eligibility requirements were as follows: (1) inclusion in LALA87 trial, (2) complete response to induction or salvage therapy, (3) age 15 to 40 years, and (4) at least one potential sibling donor. Patients with an HLA identical sibling were assigned to the BMT group, while patients without a sibling donor constituted the control group. Allogeneic transplantation was scheduled for patients in the BMT group; in the control group, patients were randomly allocated to receive chemotherapy or autologous transplantation. RESULTS: Of 284 eligible points, 257 entered the study: 116 were allocated to the BMT group and 141 to the control group. The 5-year survival rates were not statistically significantly different between the two groups. When only patients with high-risk ALL were considered (those with [1] Philadelphia chromosome [Ph1] ALL, [2] null or undifferentiated ALL, or [3] c-ALL with either age greater than 35 years or WBC count > 30 x 10(9)/L or time to achieve complete remission > 4 weeks), overall survival (P = .03) and disease-free-survival (P = .01) were better for the BMT group compared with the control group (5-year overall survival rates, 44% v 20%; 5-year disease-free survival rates, 39% v 14%). CONCLUSION: Allogeneic transplantation does not improve survival in patients with standard risk ALL and should be recommended only for patients with adverse prognostic factors. PMID- 7989933 TI - The role of pentostatin in the treatment of T-cell malignancies: analysis of response rate in 145 patients according to disease subtype. AB - PURPOSE: To assess the results of treatment with the purine analog 2'deoxycoformycin (pentostatin [DCF]) in patients with postthymic T-cell malignancies. PATIENTS AND METHODS: One hundred forty-five patients with postthymic T-cell malignancies were given DCF intravenously at 4 mg/m2/wk for the first 4 weeks and then every 2 weeks until maximal response; the last 30 patients received weekly injections until maximal response. RESULTS: The overall response rate was 32% (complete responses [CRs] plus partial responses [PRs]), with marked variation according to diagnosis. The best responses occurred in patients with Sezary syndrome (62%) and T-prolymphocytic leukemia (T-PLL) (45%), with CRs in three of 16 Sezary syndrome and five of 55 T-PLL patients. In contrast, no responses (NRs) were documented in 13 patients with other types of cutaneous T cell lymphoma, including five mycosis fungoides. Two of five patients with large granular lymphocyte (LGL) leukemia had a CR and two of four with Sezary cell leukaemia had a PR. A low response rate was observed in 27 patients with peripheral T-non-Hodgkin's lymphoma (T-NHL) (19%) and in 25 with adult T-cell leukemia/lymphoma (ATLL) (12%). The latter included two CRs and one PR. Toxicity was low and DCF was generally well tolerated. No significant differences were observed when results were analyzed according to previous treatment. Disease subtype was the most important factor to influence results. CONCLUSION: We conclude that DCF is effective as a single agent in T-PLL, Sezary syndrome, and LGL leukemia, but has low activity in other T-cell disorders. PMID- 7989934 TI - Low numbers of CSF blasts at diagnosis do not predict for the development of CNS leukemia in children with intermediate-risk acute lymphoblastic leukemia: a Childrens Cancer Group report. AB - PURPOSE: This study was designed to evaluate the effect on CNS relapse (CNSR) and overall relapse rates of blast cells in the CSF containing < or = 5 cells/microL at the time of diagnosis of intermediate-risk acute lymphoblastic leukemia (ALL) in children entered onto a large randomized multicenter prospective therapeutic trial (Childrens Cancer Group [CCG]-105). PATIENTS AND METHODS: We studied outcome in terms of CNSR and event-free survival (EFS) in 1,544 patients who successfully completed remission-induction therapy and had been randomized to one of four systemic chemotherapy regimens and to one of two CNS prophylaxis regimens. We compared outcome between 1,450 patients who had varying degrees of pleocytosis but no blasts in the CSF at diagnosis (blast-negative group) with 94 who had blasts detected in the CSF after cytocentrifugation but had a total CSF WBC count of < or = 5/microL (blast-positive group). RESULTS: No statistically significant differences in overall CNSR or EFS rates were observed between the two groups and no differences were found when analyzed according to age or WBC count at diagnosis, sex, or type of CNS prophylaxis (intrathecal [IT] methotrexate [MTX] alone v IT MTX plus 18 Gy cranial irradiation [CXRT]). CONCLUSION: In intermediate-risk ALL, there was no significant difference in CNSR and systemic relapse rates after standard presymptomatic CNS therapy between patients with a CSF WBC count < or = 5/microL and those without identifiable blasts in the CSF. These findings suggest that certain approaches to therapy, such as that used in this study, may eliminate the need for any additional special treatment directed at this subset of patients with CSF blasts. PMID- 7989935 TI - Immunologic, cytogenetic, and clinical characterization of childhood acute lymphoblastic leukemia with the t(1;19) (q23; p13) or its derivative. AB - PURPOSE: To evaluate the immunophenotypes, karyotypes, and clinical features, including treatment responses, of patients with childhood acute lymphoblastic leukemia (ALL) and either a t(1;19)(q23;p13) or a der(19)t(1;19)(q23;p13) translocation. PATIENTS AND METHODS: The lymphoblasts of 45 patients with a balanced translocation, t(1;19) or its derivative form, der(19)t(1;19), were analyzed by cytogenetic and immunologic methods for differences that might suggest distinct subtypes of ALL. This cohort was treated in four consecutive clinical trials with a median overall follow-up duration of 7 years. RESULTS: A pre-B immunophenotype was found in 10 cases with the balanced t(1;19) and 31 with the unbalanced der(19)t(1;19). The four remaining cases, each with a derivative t(1;19), were classified as early pre-B ALL. The characteristic surface antigen profile of the 41 pre-B cases was CD19+/CD10+/CD22+/CD34-/CD20+/-, whether the translocation was balanced or derivative. In contrast to the four early pre-B cases, which had hyperdiploid karyotypes (> 50 chromosomes), the pre-B cases were primarily pseudodiploid. Comparison of presenting clinical and laboratory features, as well as event-free survival, failed to disclose any differences that would warrant separation of pre-B cases with a balanced or derivative translocation. However, neither subgroup responded to therapy as well as patients with early pre-B ALL, each of whom remains in complete remission for > or = 3 years. CONCLUSION: The t(1;19) and the der(19)t(1;19) identify a relatively homogeneous group of patients with pre-B ALL, who can be expected to respond similarly to intensive chemotherapy. The exceptional cases have an early pre-B phenotype with hyperdiploid karyotypes and appear to have favorable prognosis. PMID- 7989936 TI - Osteosarcoma recurrences in pediatric patients previously treated with intensive chemotherapy. AB - PURPOSE AND METHODS: Between January 1981 and June 1993, 137 children and adolescents were each treated at the Institut Gustave Roussy for an initially nonmetastatic osteosarcoma of the extremities. We report the retrospective analysis of 42 cases of recurrence that occurred in this population. RESULTS: The median interval between the diagnosis of the primary osteosarcoma and the first recurrence was 21 months (range, 5 to 60). The site of the first recurrence was limited to the lung in 20 patients, the bone in seven patients, was local in six patients, and was confined to soft tissue in one patient. In eight patients, the first recurrence affected multiple sites. Subsequent recurrences often involved unusual or multiple sites. Management of recurrences included surgery and/or various regimens of second-line chemotherapy, and in one case involved high-dose chemotherapy followed by autologous bone marrow transplantation. Overall survival and event-free survival were, respectively, 36% and 27% at 36 months. At present, 13 patients are alive without evidence of disease. Response of the primary tumor to preoperative chemotherapy, the time between the diagnosis and the first recurrence, and the number of metastatic lesions did not correlate with survival. The survival rate is better in patients with a local or a pulmonary first recurrence. CONCLUSION: The most important prognostic indicator at first recurrence seems to be the possible complete resection of disease. Patients not amenable to surgery and patients with a second or a third recurrence have a poor prognosis. The potential benefit of more aggressive treatments such as high-dose chemotherapy and autologous bone marrow transplantation should be investigated for these patients. PMID- 7989937 TI - Neuropsychologic effects of cranial irradiation, intrathecal methotrexate, and systemic methotrexate in childhood cancer. AB - PURPOSE: To investigate the neuropsychologic effects of cranial irradiation (CRT), intrathecal methotrexate (IT-MTX), and systemic methotrexate (SYS-MTX) in a cohort of pediatric patients with cancer who had either received no, moderate, or high doses of these treatments alone or in various combinations. PATIENT AND METHODS: Data were collected on 120 pediatric cancer patients from a large variety of diagnostic groups. Patients completed a comprehensive neuropsychologic test battery designed to assess most areas of cognitive functioning. In analyzing cancer treatment effects, the following variables were statistically controlled: (1) age, (2) socioeconomic status (SES), (3) age at diagnosis, (4) months since both onset and cessation of CNS treatments, (5) time missed from schooling, and (6) presence/type of CNS cancer. RESULTS: CRT, largely in combination with IT MTX, was significantly associated with deficits in several, primarily nondominant, hemispheric neuropsychologic functions, even after control and other treatment variables were addressed. This relationship was somewhat, but not highly, dose-dependent at CRT doses greater than approximately 18 Gy, at least over the first several years posttreatment. While there was statistically significant evidence for cognitive impairment, absence from school during treatment and age at diagnosis were more predictive of reading and spelling academic achievement than having received CRT. IT-MTX and SYS-MTX alone were not associated with significant degrees of neuropsychologic involvement. CONCLUSION: CRT, especially when administered with IT-MTX, at currently used dosages was associated with significant neuropsychologic impairment in children. These impairments are most likely to be reflected in nonverbal intelligence, perceptual abilities, and susceptibility to distraction. IT-MTX and SYS-MTX did not result in a consistent pattern of cognitive deficit. PMID- 7989938 TI - Randomized trial of a chlorhexidine mouthwash for alleviation of radiation induced mucositis. AB - PURPOSE: To determine whether a chlorhexidine mouthwash could alleviate radiation induced oral mucositis. PATIENTS AND METHODS: Patients scheduled to receive radiation therapy to include greater than one third of the oral cavity mucosa were selected for study. Following stratification, they were randomized in a double-blind manner to receive a chlorhexidine mouthwash or a placebo mouthwash. Both groups were then similarly evaluated for mucositis and mouthwash toxicity. RESULTS: Twenty-five patients were randomized to receive the chlorhexidine mouthwash, while 27 received the placebo mouthwash. Treatment arms were well balanced. There was a trend for more mucositis and there was substantially more toxicity (eg, mouthwash-induced discomfort, taste alteration, and teeth staining) on the chlorhexidine arm. CONCLUSION: In contrast to the prestudy hypothesis that a chlorhexidine mouthwash might provide benefit for patients receiving radiation therapy to the oral mucosa, this study provides strong evidence suggesting that a chlorhexidine mouthwash is detrimental in this clinical situation. PMID- 7989939 TI - The role of thymidylate synthase expression in prognosis and outcome of adjuvant chemotherapy in patients with rectal cancer. AB - PURPOSE: We assessed the prognostic importance of the level of thymidylate synthase (TS) expression in patients with primary rectal cancer and whether, for Dukes' B and C cancer patients, the benefit of chemotherapy was associated with TS expression. PATIENTS AND METHODS: The level of TS expression in the primary rectal cancers of 294 of 801 patients enrolled on protocol R-01 of the National Surgical Adjuvant Breast and Bowel Project (NSABP) was immunohistochemically assessed with the monoclonal antibody TS 106. RESULTS: Forty-nine percent of patients whose tumors had low TS levels (n = 91) were disease free at 5 years compared with 27% of patients with high levels of TS (n = 203; P < .01). Moreover, 60% of patients with low TS levels were alive after 5 years compared with 40% of patients with high TS levels (P < .01). The level of TS protein was significantly associated with Dukes' stage (P < .01); patients with a more advanced Dukes' stage had a significantly higher level of TS. The level of TS expression remained prognostic for both disease-free survival (P < .01) and survival (P < .05) independent of Dukes' stage and other pathologic characteristics evaluated. Thirty-eight percent and 54% of patients with high TS levels (n = 71) were disease free and alive, respectively, after 5 years when treated with chemotherapy, compared with 17% and 31%, respectively, of similar patients when treated with surgery alone (n = 64) (P < .01). No difference was noted in disease-free survival (P = .46) or survival (P = .43) in patients with low TS levels. CONCLUSION: The expression of TS is an important independent prognosticator of disease-free survival and survival in patients with rectal cancer. Adjuvant fluorouracil (5-FU)-based chemotherapy demonstrated significant improvement in disease-free and overall survival for patients with high TS levels. Prospective studies measuring TS levels will be needed to understand further the role of TS as a prognosticator of survival and chemotherapeutic benefit. PMID- 7989940 TI - Placebo-controlled randomized trial of infusional fluorouracil during standard radiotherapy in locally advanced head and neck cancer. AB - PURPOSE: To determine whether the addition of infusional fluorouracil (I-FU) to standard radiotherapy improves survival at acceptable toxicity in patients with locally advanced squamous cell head and neck cancer (SCHNC). PATIENTS AND METHODS: Consenting patients with an Eastern Cooperative Oncology Group (ECOG) performance status < or = 2; with stage III or IV SCHNC of the oral cavity, oropharynx, hypopharynx, or larynx; and who were recommended for radiotherapy with curative intent received 66 Gy of radiation therapy delivered in 2-Gy fractions once daily 5 days per week for 6 1/2 weeks. Those in the experimental arm received I-FU 1.2 g/m2/d, as a 72-hour infusion in the first and third weeks of radiation. Saline infusions were used in the placebo arm. RESULTS: One hundred seventy-five patients were randomized (88 to I-FU and 87 to placebo), and the treatment arms were well balanced. The complete response rate was 68% for I-FU and 56% for placebo (P = .04). The overall median survival duration was 33 months for I-FU and 25 months for placebo (P = .08). Progression-free survival also favored I-FU (P = .06). Toxicity was greater in I-FU patients, but did not interfere with the scheduled delivery or completion of radiation. CONCLUSION: The addition of I-FU to standard radiation in SCHNC improved the complete response rate and was associated with beneficial trends in progression-free and overall survival compared with radiation alone. I-FU patients also experienced greater morbidity, but this did not compromise delivery of radiotherapy. PMID- 7989941 TI - European-Canadian randomized trial of paclitaxel in relapsed ovarian cancer: high dose versus low-dose and long versus short infusion. AB - PURPOSE: Taxol (paclitaxel; Bristol-Myers Squibb, Wallingford, CT) is a new anticancer agent with activity in a number of human tumors, including epithelial ovarian cancer. In nonrandomized trials, doses studied have ranged from 135 mg/m2 to 250 mg/m2 administered over 24 hours with premedication to avoid hypersensitivity reactions (HSRs). This study addressed two questions: the dose response relationship of Taxol in relapsed ovarian cancer and the safety of a short infusion given with premedication. METHODS: Women with platinum-pretreated epithelial ovarian cancer and measurable recurrent disease were randomized in a bifactorial design to receive either 175 or 135 mg/m2 of Taxol over either 24 or 3 hours. Major end points were the frequency of significant HSRs and objective response rate. Secondary end points were progression-free and overall survival. RESULTS: Of 407 patients randomized, 391 were eligible and 382 assessable for response. Analysis was performed according to the bifactorial design. Severe HSRs were rare (1.5% patients) and were not affected by either dose or schedule. Response was slightly higher at the 175-mg/m2 dose (20%) than at 135 mg/m2 (15%), but this was not statistically significant (P = .2). However, progression-free survival was significantly longer in the high-dose group (19 v 14 weeks; P = .02). Significantly more neutropenia was seen when Taxol was administered as a 24 hour infusion. Response rates were similar in the 24- and 3-hour groups (19% and 16%, respectively; P = .6). No survival differences were noted. CONCLUSION: The 3 hour infusion of Taxol is safe when given with premedication and is associated with less neutropenia. There is a modest dose effect with longer time to progression at 175 mg/m2. The observation that longer infusion produces more myelosuppression but does not yield higher response rates should lead to further studies to determine the optimal dose and schedule of this interesting new agent. PMID- 7989942 TI - Dose-ranging study of recombinant human granulocyte-macrophage colony-stimulating factor in small-cell lung carcinoma. AB - PURPOSE: This randomized, multicenter, dose-finding study was undertaken to determine the dose of recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) that can safely reduce neutropenia after cyclophosphamide, doxorubicin, and etoposide (CAVP-16) chemotherapy in patients with small-cell lung cancer (SCLC). Secondary clinical end points included incidence of infection, intravenous (IV) antimicrobial use, and chemotherapy delivered. PATIENTS AND METHODS: A total of 290 newly diagnosed SCLC patients were to receive six cycles of standard CAVP-16 chemotherapy on days 1 to 3 of every 21 days alone or with rhGM-CSF at 5, 10, or 20 micrograms/kg, administered subcutaneously (SC) on days 4 to 13 of each cycle. RESULTS: In cycle 1, median absolute neutrophil count (ANC) nadirs were twofold to threefold higher in patients who received rhGM-CSF, although all values were less than 500/microliters, and recovery from neutropenia was faster at all rhGM-CSF dosages versus observation (P < or = .01). In cycle 2, 56% of all patients given rhGM-CSF received full chemotherapy dosages (87.5% to 112.5% of projected dose) versus 36% of observation patients. During days 5 to 21 of cycle 1, fewer patients who received 10 micrograms/kg of rhGM-CSF required antibiotics compared with observation patients (11% v 29%, P < or = .01). Adverse events that occurred more frequently in rhGM-CSF-treated patients included injection-site reaction, edema, asthenia, paresthesia, diarrhea, myalgia, musculoskeletal pain, Pruritus, and rash (P < or = .10). Fever occurred more frequently in the 10- and 20 micrograms/kg rhGM-CSF groups than in the observation groups. The incidence in the 5-microgram/kg group was comparable to that in observation patients. Patients who received rhGM-CSF had a higher incidence of thrombocytopenia. CONCLUSION: rhGM-CSF at 5 to 10 micrograms/kg reduces chemotherapy-associated neutropenia and should be the dose range used in future studies. PMID- 7989943 TI - Measurable or assessable disease in lung cancer trials: does it matter? AB - PURPOSE: The goals of this study were to analyze and compare the major clinical response rates and survival of patients with either measurable or assessable disease status to treatment with systemic chemotherapy. PATIENTS AND METHODS: All patients had stage IIIB or IV non-small-cell lung cancer (NSCLC) and were enrolled onto three consecutive phase III clinical trials. Patients were stratified by disease status (measurable or assessable) before randomization to systemic chemotherapy. The three trials were conducted in the setting of a multicenter cooperative oncology group. Composite data were obtained for the three trials. Major clinical responses, time to progression, and survival were analyzed and compared in patients with measurable or assessable disease using standard statistical methods. RESULTS: Four hundred twenty-six patients were enrolled onto the three trials from June 1981 through August 1990. Measurable disease was present in 236 patients (55%) and assessable disease in 190 (45%). Each study was well balanced for the number of patients with measurable or assessable disease on either treatment regimen. A major clinical response was observed in 71 patients with measurable disease (30%; 95% confidence interval [CI], 24 to 36). Forty patients with assessable disease responded to treatment (21%; 95% CI, 16 to 28) (P = .04). The time to progression for all patients (P = .23) and for responders only (P = .10) was not significantly different based on disease status. Overall survival and survival of responders only was not significantly different, but patients with assessable disease tended to do better. Using multivariate analysis, sex and disease status had a borderline influence on the major response rate (P = .05). Performance score (PS) was the only factor that was significantly correlated with survival. CONCLUSION: NSCLC patients with assessable disease have major clinical response rates, time to progression, and survival that are similar to those of NSCLC patients with measurable disease. This study supports the inclusion of patients with assessable disease lung cancer in both phase II and III trials conducted in the cooperative group setting. PMID- 7989944 TI - Phase I trial of outpatient weekly paclitaxel and concurrent radiation therapy for advanced non-small-cell lung cancer. AB - PURPOSE: To determine the maximum-tolerated dose (MTD) and dose-limiting toxicities of paclitaxel administered weekly on an outpatient basis with concurrent thoracic radiation to patients with advanced non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: In this phase I clinical trial, paclitaxel was administered as a 3-hour intravenous (IV) infusion, repeated every week for 6 weeks. The starting dose of paclitaxel was 10 mg/m2. Doses were escalated at 10 mg/m2 increments in successive cohorts of three new patients if tolerated. Unacceptable toxicity was defined as grade 3 nonhematologic toxicity, excluding nausea and vomiting, and grade 4 hematologic toxicity according to Cancer and Leukemia Group B expanded common toxicity criteria. Radiation was administered to the primary tumor and regional lymph nodes (40 Gy) followed by a boost to the tumor (20 Gy). RESULTS: Twenty-seven patients were entered onto this study through seven dose escalations (from 10 mg/m2/wk to 70 mg/m2/wk for 6 weeks). Severe esophagitis occurred at 70 mg/m2 (two patients with grade 4 disease and one patient with grade 2). One of six patients at 60 mg/m2 developed grade 3 esophagitis and three of seven patients had grade 2 esophagitis. One of 27 patients developed a hypersensitivity reaction. One of 27 patients developed grade 3 neutropenia. CONCLUSION: Esophagitis is the principle dose-limiting toxicity of weekly paclitaxel and thoracic radiation in the outpatient setting. A phase II trial using concurrent radiation and paclitaxel at the MTD of 60 mg/m2/wk is underway. PMID- 7989945 TI - Fluorouracil, doxorubicin, and mitomycin combination versus PELF chemotherapy in advanced gastric cancer: a prospective randomized trial of the Italian Oncology Group for Clinical Research. AB - PURPOSE: The combination of cisplatin, epirubicin, and leucovorin preceding fluorouracil (PELF) includes three novel agents compared with the standard combination of fluorouracil, doxorubicin, and mitomycin (FAM) in the treatment of advanced gastric carcinoma. We report the results of a prospective randomized comparison of the two combinations in previously untreated patients. PATIENTS AND METHODS: One hundred thirty assessable patients were entered onto the trial; 52 received FAM and 85 PELF. A 1:2 unbalanced randomization in favor of the experimental treatment was chosen. Approximately 90% of patients had measurable tumor masses. RESULTS: The overall response rates (complete responses [CRs] and partial responses [PRs]) were 15% and 43% for the FAM and the PELF regimens, respectively, with a statistically significant advantage for the experimental treatment (P = .001). Time to progression (median, 2.6 and 4.7 months), duration of response (median, 10.7 and 10.2 months), and survival durations (median, 5.6 and 8.1 months) were not significantly different between the FAM and PELF regimens, respectively. The PELF combination was more toxic compared with FAM, but generally tolerable. CONCLUSION: This study showed that the PELF combination is about three times more effective than the FAM combination in inducing objective responses. Due to tolerability, it is not recommended for routine clinical use. However, it should be considered, among other second-generation chemotherapy combinations, in future randomized studies aimed to improve the therapeutic outcome in gastric carcinoma. PMID- 7989946 TI - Primary therapy of Waldenstrom's macroglobulinemia with 2-chlorodeoxyadenosine. AB - PURPOSE: To assess the activity of 2-chlorodeoxyadenosine (2CdA) as primary therapy for patients with Waldenstrom's macroglobulinemia. PATIENTS AND METHODS: 2CdA was given to 26 consecutive, previously untreated and symptomatic patients with Waldenstrom's macroglobulinemia. Two courses were administered to outpatients at a dose of 0.1 mg/kg body weight per day for a 7-day continuous infusion using a portable pump through a central venous catheter. Responding patients were followed up without further therapy and were scheduled to receive two additional treatments with 2CdA on disease relapse. RESULTS: Twenty-two of 26 patients responded to the 2CdA therapy (85%; 95% confidence interval [CI], 65% to 96%), including three patients who achieved a complete response and 19 patients who had a partial response. Treatment was well tolerated, with no acute hematologic toxicity. A marked and sustained reduction of CD4+ lymphocytes occurred in all patients and may have contributed to a fatal infection with disseminated herpes simplex in one patient. With a median follow-up of 13 months, five patients have relapsed and all re-treated patients have responded again to 2CdA. CONCLUSION: 2CdA is highly active in previously untreated patients with Waldenstrom's macroglobulinemia. A limited program of treatment induced responses of good quality and long duration in more than 80% of patients. PMID- 7989947 TI - Relationship of chemotherapy-induced necrosis and surgical margins to local recurrence in osteosarcoma. AB - PURPOSE AND METHODS: To assess patients with high-grade osteosarcoma treated at our institution for various prognostic factors for the development of local recurrence of disease. Follow-up data were available for all patients and the mean follow-up duration was 65 months in surviving patients. RESULTS: There were 28 local recurrences in this study (7%). Of these, only three patients (11%) were alive at the most recent follow-up point, 28, 53, and 54 months after local recurrence. None of 59 patients who were treated primarily with a radical amputation and none of 10 who underwent a rotationplasty developed local recurrence. Four of 48 patients (8%) who had wide amputations, one of whom had an intralesional amputation, and 23 of 237 (10%) who had limb-salvage surgery developed locally recurrent disease. Of 237 patients who underwent limb-sparing resection, three prognostic factors for local control were identified. The strongest association with local recurrence was chemotherapy response (P < .0001), followed closely by surgical margins (P = .0001). Older patients were more likely to have locally recurrent disease (P = .033), with each decade of life older than the first decade having a relative risk of 1.5 times greater per decade (SE = 0.16; 95% confidence interval, 0.034 to .0650). Factors that were not associated with local recurrence included sex, date of diagnosis, and anatomic site of disease. CONCLUSION: Chemotherapy-induced tumor necrosis and surgical margins are important prognostic factors for local control of patients with osteosarcoma. PMID- 7989948 TI - VAD-PECC regimen in the treatment of advanced-stage multiple myeloma. AB - PURPOSE: This prospective study was undertaken to evaluate the efficacy of combination chemotherapy with alternating cycles of vincristine, doxorubicin, and dexamethasone (VAD) and prednisone, vindesine, carmustine, and cyclophosphamide (PECC) in poor-risk multiple myeloma (MM). PATIENTS AND METHODS: Forty-four patients were previously untreated; 36 had been pretreated with an alkylating agent-containing regimen and had refractory or relapsed MM. All previously untreated patients had a high tumor burden at inclusion (stage III according to the Durie and Salmon classification). Logistic regression and the Cox proportional hazards models were used to assess the association between patient characteristics and response rate and survival, respectively. RESULTS: The overall response rate was 68% for previously untreated patients, compared with 54% for previously treated patients (P = .16). The median survival time for all patients was 28 months: 53 months in previously untreated patients, and 18 months in previously treated patients. Univariate analysis showed that the predictive factors that had a significant affect on survival in the newly diagnosed patients were age, therapeutic response to VAD-PECC, low pretreatment Karnofsky score, high baseline serum beta 2-microglobulin (beta 2M) level, bone marrow impairment, and renal insufficiency at the start of treatment. When these parameters were used as continuous variables in multivariate analysis, three were found to correlate with survival: serum beta 2M, followed by therapeutic response and Karnofsky score. In the previously treated group, only Karnofsky score entered the Cox model. CONCLUSION: These results indicate that combination VAD-PECC chemotherapy is an effective treatment that results in high response rates and long-term survival in advanced MM. PMID- 7989949 TI - Renal dysfunction associated with the administration of high-dose interleukin-2 in 199 consecutive patients with metastatic melanoma or renal carcinoma. AB - PURPOSE: To describe the incidence and management of renal dysfunction associated with the use of high-dose interleukin-2 (IL-2) (as is currently approved) in the treatment of cancer patients. PATIENTS AND METHODS: One hundred ninety-nine consecutive patients with metastatic renal carcinoma or melanoma were treated with intravenous bolus infusions of IL-2 alone (720,000 IU/kg) every 8 hours. RESULTS: Patients received 310 courses (589 cycles) of therapy and most experienced oliguria, hypotension, and weight gain; 13% of cycles were discontinued due to increased serum creatinine levels. Creatinine values (mean pretherapy, 1.2 mg/dL) increased during therapy and peaked (mean, 2.7 mg/dL) approximately 1 day after discontinuation of the second cycle of IL-2. Off therapy, toxicities reversed promptly and creatinine values returned to baseline. Higher peak creatinine values occurred in patients with renal carcinoma (v melanoma), older patients, males (v females), and those who had undergone prior nephrectomy. These same patient subsets received fewer doses of IL-2, but clinical responses were not associated with creatinine values or number of IL-2 doses administered. Urinalyses showed the appearance of protein, bilirubin, RBCs, WBCs, and granular casts during therapy, which cleared completely on follow-up evaluation. CONCLUSION: High-dose IL-2 can be safely administered to cancer patients. The associated renal dysfunction is transient and without evidence of intrinsic long-term renal damage. Practical guidelines for patient management have been identified. PMID- 7989950 TI - Percutaneous hepatic vein isolation and high-dose hepatic arterial infusion chemotherapy for unresectable liver tumors. AB - PURPOSE: This prospective, nonrandomized trial evaluated a percutaneous isolated chemotherapy perfusion approach for treating advanced primary and metastatic liver tumors. Chemotherapy was administered via hepatic artery catheter and hepatic venous blood isolated by a novel percutaneous double-balloon inferior vena cava (IVC) catheter was passed through a detoxification/filtration cartridge in a venovenous bypass circuit. PATIENTS AND METHODS: Among 23 patients enrolled onto the study, 58 procedures were performed on 21 patients. Twelve patients received dose escalations of fluorouracil (5-FU) (1,000 mg/m2 to 5,000 mg/m2), and nine received dose escalations of doxorubicin (50 mg/m2 to 120 mg/m2). Pharmacokinetic studies included drug accumulation in the liver, extraction by detoxification filters, systemic exposure, and alterations of half-life. Each patient received two treatments at 3-week intervals. Those showing stabilization or response received additional treatments. RESULTS: There was a direct relationship between dose and peak concentration of drug entering the hepatic veins. The system functioned efficiently throughout the dose range, with extraction efficiencies ranging from 64% to 91% (P < .001). The hepatic vein drug levels showed a sixfold increase in 5-FU with dose escalation from 1,000 to 5,000 mg/m2, and a twofold increase in dox with dose escalation from 50 to 120 mg/m2 (P < .001, filter-mediated drug extraction). The treatments were accomplished with only an overnight hospital stay and no mortality. The common procedure-related toxicity was transient hypotension (grade I to II), due to catecholamine depletion by the filter. Dose-limiting toxicity (leukopenia) was observed in patients receiving 5-FU at a dose of 5,000 mg/m2 and doxorubicin at a dose of 120 mg/m2. Significant tumor response (> 95% reduction) was obtained in two patients receiving doxorubicin at 90 mg/m2 and 120 mg/m2. CONCLUSION: The use of a double balloon catheter to isolate and detoxify hepatic venous blood during intraarterial therapy is technically feasible, safe, and allows administration of large doses of intrahepatic chemotherapy at short intervals. This approach should allow new dose-intensification strategies to increase tumor responses in primary and metastatic liver tumors. PMID- 7989951 TI - Salvage surgery for chemorefractory gestational trophoblastic disease. AB - PURPOSE: To investigate and define better the role of salvage surgery for patients with chemorefractory gestational trophoblastic disease (GTD). PATIENTS AND METHODS: A retrospective review of medical records at The University of Texas M.D. Anderson Cancer Center identified 33 patients with chemorefractory GTD who underwent salvage surgery between 1962 and 1991. The end points selected for analysis were serologic response and survival. RESULTS: Initial salvage procedures consisted of 29 hysterectomies, four thoracotomies, and one nephrectomy (in conjunction with a hysterectomy). Fourteen patients (42%) had a serologic complete response (CR) to surgery (normalization of human chorionic gonadotropin [hCG]), 10 (30%) had a partial response (> 50% decrease in hCG level), and nine had no response (< or = 50% decrease in hCG level). Of 19 patients who received further chemotherapy, eight (42%) attained a CR. Four patients underwent a second salvage surgery: two thoracotomies, one craniotomy, and one partial hepatectomy. All achieved a CR. The probability of achieving a CR was influenced by the time from diagnosis to surgery, number of preoperative disease sites, preoperative World Health Organization (WHO) score, and histologic type. Survival was influenced by the type of antecedent pregnancy, number of preoperative regimens, number of preoperative disease sites, time from diagnosis to surgery, and preoperative WHO score. CONCLUSION: Based on the findings of this study, it appears that a select subset of patients with chemorefractory GTD who have a limited number of clinically detectable tumor foci may benefit from salvage surgery. PMID- 7989952 TI - Regular use of a verbal pain scale improves the understanding of oncology inpatient pain intensity. AB - PURPOSE: This study was undertaken to determine if the daily use of a verbal pain scale could improve the correlation of pain perception between hospitalized oncology patients and their caregivers. PATIENTS AND METHODS: Hospitalized oncology patients were asked to rate verbally their average pain over the past 24 hours on a scale ranging from 0 to 10. The patients' primary-care physicians and nurses were asked the same question on the same morning after they had evaluated their patients. RESULTS: During a baseline study, only 64% of caregivers' pain scores were within two points of the respective patient's score. Caregivers tended to underestimate patients' pain scores. Caregivers were alerted to these poor results and then requested to ask each patient daily for the average pain score and record this score on the patient's medical record. Nonetheless, correlation between patients' and caregivers' pain scores remained poor (68% within two points of each other) during a second study. The major reason for the poor results appeared to be because caregivers did not routinely ask patients for pain scores. Subsequently, a renewed, more intensive educational effort was undertaken and a third study was conducted. During the third study, 85% of caregivers' and patients' pain scores were within two points of each other (P = .001 when compared with baseline). CONCLUSION: The enforced use of a simple verbal pain assessment tool appears to improve caregiver's understanding of the pain status of hospitalized oncology patients. PMID- 7989953 TI - Efficacy and safety of nonsteroidal antiinflammatory drugs for cancer pain: a meta-analysis. AB - PURPOSE: To assess the efficacy and safety of nonsteroidal antiinflammatory drugs (NSAIDs) in the treatment of cancer pain by meta-analyses of the published randomized control trials (RCTs). PATIENTS AND METHODS: Twenty-five studies met inclusion criteria for analysis. Of these, 13 tested a single-dose effect, nine multiple-dose effects, and three both single- and multiple-dose effects of 16 different NSAIDs in a total of 1,545 patients. Baseline pain intensity (when provided) of moderate or higher was indicated in 81% of patients. RESULTS: Single dose NSAID studies found greater analgesic efficacy than placebo, with rough equivalence to 5 to 10 mg of intramuscular morphine. Pain scores differed insignificantly for aspirin versus three other NSAIDs. Analgesic responses to low and high-dose NSAIDs suggested a dose-response relationship, but this was not statistically significant. Recommended and supramaximal single doses of three NSAIDs produced comparable changes in pain scores, which indicates a ceiling analgesic effect. Common side effects included upper gastrointestinal symptoms, dizziness, and drowsiness. The incidence of side effects showed a trend to increase with dose, without a ceiling effect, and to increase with multiple doses. Single or multiple doses of weak opioids (WO) alone or in combination (WO/C) with nonopioid analgesics did not produce greater analgesia than NSAIDs alone. Single doses of WO/C analgesics produced more side effects than NSAIDs alone, although both side effect incidence and patient dropout rates were equal when multiple doses were administered. CONCLUSION: These findings question whether the traditional World Health Organization (WHO) second analgesic step (addition of a weak opioid when pain is inadequately treated by a nonopioid analgesic alone) is warranted. A lack of comparable studies precluded testing the hypothesis that NSAIDs are particularly effective for malignant bone pain. PMID- 7989954 TI - ESHAP chemotherapy for relapsed/refractory non-Hodgkin's lymphoma. PMID- 7989955 TI - The International Index is not useful in the classification of low-grade lymphoma. PMID- 7989956 TI - Safety, pharmacokinetics, and pharmacodynamics of high-dose etoposide. PMID- 7989957 TI - Actions speak louder than words. PMID- 7989958 TI - A synopsis of the origins and function of dental plaque and pellicle. PMID- 7989959 TI - Relationship between oral hygiene state and levels of oral sensory perception and motor ability. AB - It has been postulated that subjects with high levels of oral sensory perception and motor ability are able to achieve higher standards of oral hygiene even under different dietary regimes. In this study, eleven dental personnel volunteers were started on a low-sucrose diet for one week, followed by a high-sucrose diet for another week, while eleven others followed a reverse-order dietary regime. Oral sensory perception and motor ability were assessed by the oral stereognosis test and a test for oral motor ability. There was a greater trend for subjects to have more plaque on their teeth when they were on the high-sucrose diet, even when normal oral hygiene procedures were taken. There were no significant correlations between the state of oral hygiene and levels of oral sensory perception and motor ability. These results do not support the hypothesis that subjects with high levels of oral sensory perception and motor ability are likely to achieve better oral hygiene. PMID- 7989960 TI - Comparison of the antibacterial effects on subgingival microflora of two different resorbable base materials containing doxycycline. AB - A study was conducted to evaluate the effects of local drug delivery on subgingival plaque flora using hydroxypropylmethylcellulose (HPMC) and methylcellulose (MC) base material containing 40% doxycycline (DOXY). Eleven patients who had at least four pockets exceeding 5 mm in depth associated with a single rooted tooth were selected from volunteers after an initial examination. Two of the pockets were chosen at random for insertion of the HPMC and MC strips twice a week for 6 w. One pocket received no treatment, and the other was debrided and root-planed only. Baseline and follow-up measurements at 0, 1, 3, 6, and 10w included probing depth, gingival shrinkage, bleeding on probing and crevicular fluid flow. Subgingival bacterial samples were also taken for dark field microscopy. In vitro drug release from the HPMC strips was greater than that from MC. Significant improvements in many clinical parameters occurred in the pockets treated with HPMC or MC strips, or mechanical debridement. There was a marked decrease in the relative proportions of motile organisms during and after treatment. PMID- 7989961 TI - Use of membranes containing 20% chlorhexidine and 40% doxycycline for treatment of chronic periodontal pockets. AB - A study was carried out to compare the effects of subgingival applications of resorbable hydroxypropylmethylcellulose (HPMC) membranes containing 20% chlorhexidine (CHx) and 40% doxycycline (DOXY) placed subgingivally in periodontal pockets greater than 5 mm in depth. Each of 11 patients had at least four pockets. HPMC strips containing CHx and DOXY were inserted into each pocket twice a week for 6 w. One pocket was kept as a control and the other received subgingival scaling and root planing at 0, 1, 3 and 6 w. The microbial flora of 44 pockets from the 11 patients was examined using dark-field microscopy at the baseline and at 1, 3, 6 and 10 w. Clinical parameters including probing depth, crevicular fluid flow, bleeding on probing and gingival shrinkage were also recorded. The CHx and DOXY-administered or root-planed pockets showed marked reduction of both pocket depth and the number of motile organisms. Less bleeding was also observed in CHx and DOXY-inserted pockets. PMID- 7989962 TI - Effect of smear layer removal agent and/or fluoride on the surface of dentin. AB - A study was conducted to observe the effectiveness of an EDTA-based agent, Tubulicid Red, and a polyacrylic acid-based agent, Dentin Conditioner, for removal of the smear layer from a prepared dentin surface, with or without a fluoride dentin reinforcing agent, using the dye penetration test and scanning electron microscopy (SEM). Bovine mandibular first and second incisors were used. After removal of the enamel, the smear layer on the dentin surface was treated with 38% H3PO4, Tubulicid Red, Dentin Conditioner, 1% NaF, 1% SnF2, Tubulicid Red (including 1% SnF2), Dentin Conditioner (including 1% NaF) and Dentin Conditioner (including 1% SnF2). In the dye penetration test, Dentin Conditioner (including 1% SnF2) was the most effective agent for preventing dye penetration. SEM evaluation of the dentin surface after treatment with the smear layer removal agents and/or fluorides showed that the smear layer was removed by H3PO4 and Dentin Conditioner. However, dentinal plugs remained after treatment with Dentin Conditioner alone. The other agents left some layers on the dentin surface. PMID- 7989963 TI - Subgingival plaque formation on single and polycrystal aluminum ceramics. AB - A study was conducted to investigate subgingival plaque formation on two types of dental implant material in the human oral cavity. Fifteen teeth affected by severe periodontitis and scheduled for extraction in five patients were selected. After thorough root planing, inlay cavities were prepared from the gingival margin to 5 mm subgingivally. Then, rectangular test specimens (polycrystal aluminum ceramic (P), single-crystal aluminum ceramic (S)) or a control dentin specimen (D) were installed in gold inlays, which were placed in the inlay cavities and left for 3, 7 or 21 d. As a consequence, 4 mm of the surface of each specimen was exposed to the environment of the periodontal pocket. After each test period, the specimens were removed from the inlays and examined by scanning electron microscopy (SEM). The results suggested that S is a more suitable dental implant material than P from the viewpoint of clinical application because of its lower degree of plaque accumulation. PMID- 7989964 TI - A case of open bite accompanied by temporomandibular joint disorder. A comparison of occlusal conditions before and after treatment in lateral-oblique radiogram. AB - According to the authors' clinical experience, malocclusion accompanied by temporomandibular joint disorder involves mainly cross bite, open bite, deep overbite or axillary protrusion. However, it is possible that the symptoms of this disorder are associated with other types of malocclusion or even with nearly normal occlusion. In fact, it can be said that temporomandibular joint disorder may develop with any type of occlusion. This paper reports a case of open bite accompanied by temporomandibular joint disorder occurring in a patient who visited our hospital because of pain in the left temporomandibular joint region, vertigo and partial deafness. In this patient, the temporomandibular symptoms disappeared after orthodontic treatment. The patient received no particular treatment thereafter because follow-up observation confirmed that the therapeutic results were favorable without any relapse of the symptoms of temporomandibular disorder. The positions of the temporomandibular joint and mandibular condyle were determined in lateral-oblique radiograms obtained using our radiographic system, by which the mandibular condyle is radiographed using a projection consistent with its long axis. PMID- 7989965 TI - Taking brain SPECT seriously: reflections on recent clinical reports in The Journal of Nuclear Medicine. PMID- 7989966 TI - Ictal and interictal brain SPECT imaging in epilepsy using technetium-99m-ECD. AB - The aim of this study was to evaluate the use of 99mTc-ethyl cysteinate dimer (ECD), also known as 99mTc-bicisate, in the presurgical evaluation of patients suffering from medically intractable epilepsy. METHODS: Twenty-three brain SPECT studies (8 ictally and 15 interictally) were performed on 16 patients with a high resolution annular SPECT system (CERASPECT). For the ictal studies, the tracer was injected in the very early phase of the seizure. The delay between seizure onset and 99mTc-ECD injection was 2-20 sec. RESULTS: Interictally, all patients showed circumscribed hypoperfusions. In four patients, the SPECT lesion represented only structural defects. Circumscribed increased tracer uptake was observed in all ictal studies. For all patients with temporal lobe epilepsy without significant mass lesion, in whom an interictal and ictal 99mTc-ECD-SPECT study could be obtained, the asymmetry index was 0.88 +/- 0.03 for the interictal and 1.23 +/- 0.08 for the ictal studies. CONCLUSION: The data suggest that 99mTc ECD is an effective marker of cerebral perfusion imaging in epilepsy. In comparison to other tracers, it has a high in vitro stability and is therefore particularly useful for ictal studies in the very early phase after seizure onset. PMID- 7989967 TI - Gender differences in cerebral perfusion in cocaine abuse: technetium-99m-HMPAO SPECT study of drug-abusing women. AB - Cocaine abuse continues to be a major public health concern, with a variety of medical and neurologic sequelae. Previous studies have demonstrated abnormalities in cerebral perfusion in chronic cocaine abusers and after acute administration of cocaine. Although women are becoming increasingly represented among drug abusers, few studies have included women. To the authors' knowledge, none has compared cerebral perfusion in asymptomatic women with that in men. METHODS: The cerebral perfusion of 13 cocaine-dependent women, 4 of whom were also heroin dependent, was studied with 99mTc hexamethylpropyleneamine oxime (HMPAO) SPECT. These women were compared with 13 cocaine-dependent men and 26 healthy control subjects. Structural brain lesions and neurologic abnormalities were excluded by MRI and neurologic evaluation. Perfusion studies were interpreted in a standardized fashion by reviewers blinded to clinical information. RESULTS: It was found that cocaine-dependent women were much less likely to have abnormal study findings than cocaine-dependent men (p = 0.003) and were indistinguishable from normal women (p = 1.0). However, the results in both women and men who concurrently used heroin plus cocaine were all abnormal. Perfusion abnormalities tended to be located in anterior brain structures, such as the frontal and temporal cortex and the basal ganglia. CONCLUSION: These data suggest that cocaine-dependent women have fewer abnormalities in cerebral perfusion than cocaine-dependent men, but that concurrent abuse of heroin and cocaine is associated with more perfusion abnormalities in both sexes. PMID- 7989968 TI - Clinical application and quantitative evaluation of generator-produced copper-62 PTSM as a brain perfusion tracer for PET. AB - Copper-62-pyruvaldehyde bis(N4-methylthiosemicarbazone) copper II (62Cu-PTSM) has been proposed as a generator-produced positron-emitting tracer for perfusion imaging. To evaluate the characteristics of 62Cu-PTSM as a cerebral perfusion tracer, brain PET images of 62Cu-PTSM were compared with cerebral blood flow (CBF). METHODS: Following an intravenous injection of 62Cu-PTSM, a serial dynamic PET scan was performed for 10 min with arterial sampling in 10 subjects. CBF was measured by 15O-labeled water before the 62Cu-PTSM study. RESULTS: Dynamic PET scan with octanol-extracted arterial input function indicated the presence of significant back-diffusion of 62Cu-PTSM from the brain within 3 min after injection, followed by stable activity from 3 to 10 min. Comparison with 15O water PET demonstrated less contrast between high- and low-flow regions in 62Cu PTSM image and a nonlinear relationship of flow and 62Cu-PTSM uptake, which suggests the underestimation of CBF in high-flow regions due to the existence of back-diffusion. CONCLUSION: Although 62Cu-PTSM can be used widely for evaluation of brain perfusion with PET, kinetic analysis and correction may be needed to quantify regional CBF. PMID- 7989969 TI - PET studies on dopamine D1 receptors in the human brain with carbon-11-SCH 39166 and carbon-11-NNC 756. AB - PET studies were carried out on brain dopamine D1 receptors using two new ligands, [11C]SCH 39166 and [11C]NNC 756. METHODS: Four normal subjects and eight predominantly unilateral patients with early Parkinson's disease were investigated. Each of them underwent both a PET scan with [11C]SCH 39166 and one with [11C]NNC 756. A dose of about 185 MBq (5 mCi) of these ligands was administered intravenously and a dynamic PET scan with an ECAT 931/08 PET camera was carried out. Ratios between the striatal and cerebellar uptake of these compounds were calculated. RESULTS: Both [11C]SCH 39166 and [11C]NNC 756 accumulated in the striatum. There was also some neocortical binding; 75% of the striatal value in the case of [11C]SCH 39166 and 60% with [11C]NNC 756 which displayed higher (p < 0.01) uptake in the striatum than [11C]SCH 39166. There were no significant side-to-side differences in the controls nor in the parkinsonian patients. CONCLUSIONS: These results imply that both [11C]SCH 39166 and [11C]NNC 756 can be used in PET studies for the visualization and quantification of dopamine D1 receptors. Since [11C]NNC 756 has a significantly better signal-to-noise ratio in the striatum than [11C]SCH 39166, it seems to offer definite advantages for studies of D1 receptors. PMID- 7989970 TI - Dopamine D2 receptor imaging with iodine-123-iodobenzamide SPECT in idiopathic rotational torticollis. AB - The cause of idiopathic rotational torticollis (IRT) is not completely understood to date. However, basal ganglia are believed to be involved in the pathophysiology of IRT. To elucidate this disorder further, the value of iodobenzamide (IBZM) SPECT was studied for the evaluation of striatal dopamine D2 receptors in these patients. METHODS: Striatal dopamine D2 receptor density was assessed in 10 patients with IRT using 123I-IBZM SPECT. The images were interpreted by a nuclear medicine physician initially to determine IBZM binding within the striatum and the cerebellum and, secondly, interstriatal IBZM binding. The results were correlated with the clinical parameters of the patients and compared with the results obtained from normal controls. RESULTS: No difference was found in average, specific striatal IBZM binding (basal ganglia/cerebellum ratio) between patients and controls. However, interstriatal analysis of IBZM binding revealed a significantly higher binding in the striatum contralateral to the direction of the torticollis (p = 0.026, by chi-square test). CONCLUSION: It was concluded that the striatal dopamine D2 receptor status is altered in patients with IRT. PMID- 7989971 TI - Incidence of pulmonary embolism in single segmental mismatch on lung scanning. AB - Controversy exists as to whether patients with single segmental mismatch (SSM) on a ventilation/perfusion (VQ) lung scan should be given a low or an intermediate probability of pulmonary embolism (PE). METHODS: Pulmonary angiography was used to evaluate the incidence of PE in SSM at the authors' institution. From January 1991 to January 1993, 1449 VQ scans were performed. RESULTS: With modified Biello criteria, 283 were high probability; 628, low probability; 273, normal; and 273, intermediate probability. Of the intermediate probability scans, 61 had SSM. Forty of these patients underwent pulmonary angiography. Twelve patients had PE in the area of the SSM, giving an incidence of PE of 30%. The risk of PE in SSM in the different lung regions was also analyzed. Twenty-three SSM were in the bases of the lung with a 22% incidence of PE; 17 SSM were either in the midzone or apex with a 41% incidence of PE (p = not significant). CONCLUSION: SSM carries a 30% risk of PE. Accordingly, SSM should be given an intermediate probability of PE and not a low probability of PE. PMID- 7989972 TI - V/Q imaging and the diagnosis of PE: "can we shift the gray to black and white?". PMID- 7989973 TI - Early pulmonary involvement in systemic sclerosis assessed by technetium-99m-DTPA clearance rate. AB - Systemic sclerosis (SS) is frequently associated with interstitial lung disease, but clinical symptoms and radiologic abnormalities may occur late in the course of the disease. This study investigated early pulmonary involvement by assessing the clearance rate of inhaled 99mTc-diethylenetriaminepentaacetic acid (DTPA). METHODS: Sixteen patients with proved SS, no clinical pulmonary symptoms and normal chest radiogram were prospectively studied. The 99mTc-DTPA clearance rate was calculated as the time to half clearance (T1/2) and compared with values obtained in healthy nonsmokers. RESULTS: Six patients showed abnormally increased clearance (T1/2 < 53 min). Rapid clearance was not correlated to SS disease duration or to abnormal pulmonary function tests. Five of six patients with abnormally increased clearance underwent high-resolution CT, which in all five demonstrated pathologic findings that were suggestive of early interstitial disease. CONCLUSION: These findings indicate that in SS asymptomatic patients may frequently present with abnormal 99mTc-DTPA clearance; 99mTc-DTPA lung scintigraphy may allow early detection of subclinical pulmonary involvement in SS. PMID- 7989974 TI - Left ventricular functional reserve in nonobstructive hypertrophic cardiomyopathy: evaluation by continuous left ventricular function monitoring. AB - The cardiac functional response to exercise in patients with nonobstructive hypertrophic cardiomyopathy (HCM) was evaluated using a continuous ventricular function monitor with a cadmium telluride detector (CdTe-VEST). METHODS: Supine ergometric exercise was performed under CdTe-VEST monitoring in 41 patients with nonobstructive HCM (34 men and 7 women, age 18-72 yr, mean 51 yr) and 15 patients without cardiac disease (9 men and 6 women, age 36-56 yr, mean 49 yr). RESULTS: Although 20 of 41 patients with HCM maintained a LVEF above baseline at peak exercise (Group A), 21 did not show an EF increase at peak exercise (Group B). Exercise duration and work load in Group A were longer and higher, respectively, than in Group B. Resting EF in Group B (72 +/- 7.7%) was significantly higher than that in Group A (65 +/- 8.2%) and the control group (62 +/- 5.9%). The EF increase from baseline to EF overshoot during recovery and the time to EF overshoot were lower and longer, respectively, in Group B than in Group A and the control group. Septal wall thickness and the septum-to-posterior-wall-thickness ratio between Groups A and B were not different. ST-segment depression was observed in all 21 Group B patients and in 8 of the Group A patients. CONCLUSION: In patients with nonobstructive HCM, left ventricular dysfunction during exercise and during recovery was frequently observed but was not related to the degree of septal wall hypertrophy. The CdTe-VEST is a useful means to evaluate left ventricular functional reserve to exercise in patients with HCM. PMID- 7989975 TI - Radioiodine therapy for well-differentiated thyroid cancer: a quantitative dosimetric evaluation for remnant thyroid ablation after surgery. AB - The influence of cumulative absorbed dose, initial dose rate and mass of the remnant thyroid tissue on outcome of radioiodine treatment was assessed to determine an optimum value of absorbed dose and initial dose rate predictive of successful ablation. METHODS: In 87 patients with thyroid carcinoma treated with 0.85-9.55 GBq (23-258 mCi) of 131I to ablate residual thyroid tissue, the cumulative absorbed dose and the initial dose rate were calculated. Following therapy, the parameters of radioactive iodine uptake and effective half-life were determined in each patient from the surface neck exposure rates measured using a beta/gamma exposure rate meter. Mass of the thyroid remnant was determined from rectilinear images after scatter correction obtained from phantom studies. RESULTS: Sixty-eight patients showed complete ablation and 19 showed partial ablation of the thyroid remnant after radioiodine therapy. The cumulative absorbed doses delivered to the tissue in completely ablated and partially ablated groups were not significantly different (0.6 > p > 0.5). The initial dose rate delivered to the tissue in both groups, however, showed a significant difference (0.05 > p > 0.02). An initial dose rate of 3 Gy/hr or more completely ablated up to 5 g of tissue in 54 out of 62 patients (87.1%). Dose rate above 3 Gy/hr and cumulative doses above 300 Gy resulted in ablation in 50% of patients with more than 5 g of tissue. CONCLUSION: In patients receiving 131I to ablate thyroid remnant, the initial dose rate and the tissue mass are determinants of successful treatment response. PMID- 7989976 TI - Evaluation of technetium-99m-L,L-EC in renal transplant recipients: a comparative study with technetium-99m-MAG3 and iodine-125-OIH. AB - The clinical usefulness of kit-formulated 99mTc-L,L-EC, a new renal tubular tracer agent based on a diaminodithiol ligand was evaluated in a large population of renal transplant recipients. METHODS: Fifty patients with transplants were studied. Five patients with renal insufficiency and five normal volunteers were also included to extend the range of renal function values. The labeling efficiency of 99mTc-L,L-EC in routine conditions, i.e., without HPLC purification, and the safety of the tracer were evaluated. RESULTS: The mean radiochemical purity of 99mTc-L,L-EC determined by thin-layer chromatography was 97.4%. No side effects or significant biochemical changes were observed. The clearance of 99mTc-L,L-EC and 125I-OIH ranged from 10.7 to 417.5 and from 27.6 to 602.7 ml/min/1.73 m2, respectively. The clearance of 99mTc-L,L-EC and 99mTc-MAG3 averaged respectively 71% and 52% of that of 125I-OIH. CONCLUSION: The labeling procedure of kit-formulated 99mTc-L,L-EC is easy and efficient. This tracer is safe and suitable for both imaging and quantitative measurement of the renal tubular function. Technetium-99m-L,L-EC represents an excellent alternative to 99mTc-MAG3. PMID- 7989977 TI - Dynamic renal imaging with technetium-99m-sestamibi in hypertension: potential for assessment of renovascular disorders. AB - The myocardial perfusion agent, 99mTc-sestamibi (MIBI), offers the potential to combine renal and myocardial imaging because of high initial renal extraction and significant renal clearance. METHODS: Dynamic renal imaging was performed during rest MIBI injections in 3 normal subjects (NS) and 91 patients referred for cardiac assessment. Ten served as normal controls, and 81 were hypertensive. Renal activity of MIBI during the first transit, uptake and excretory phases of the study was quantified. These data were compared with the normal kinetics of 99mTc-diethylenetriaminepentaacetic acid (DTPA) in concurrent studies. RESULTS: With MIBI, clear definition of the kidneys was possible on all phases in most studies; occasionally, overlap with liver or spleen provided a minor problem. Renal MIBI activity reached levels 70% greater than DTPA during first transit and remained higher throughout the study; renal/background activity ratios were also higher on the MIBI study (p < 0.001). During the excretory phase with MIBI, hepatic and splenic activity did not decline, and gut activity increased. In NS, 40% of the total activity was excreted in the urine in 1 hr; urinary MIBI clearances approximated creatinine clearance. Asymmetry in initial renal uptake was seen in 14 of 81 hypertensive patients (17%); renal cysts and aortic dilatation could also be identified. CONCLUSION: These data suggest that ancillary renography during rest injection of MIBI could be a useful addition to the cardiovascular assessment of selected patients. PMID- 7989978 TI - Value of fluorine-18-FDG-PET to monitor hepatocellular carcinoma after interventional therapy. AB - METHODS: Thirty-two tumors in 30 patients with hepatocellular carcinoma (HCC) were studied preoperatively using PET with 18F-labeled 2-fluoro-2-deoxy-D-glucose (FDG) to evaluate the metabolic activity of the lesions after interventional therapy. All patients had received transcatheter arterial chemoembolization therapy using iodized oil (Lipiodol, Laboratoire Guerbet, Alnaysous-Bois, France) before the PET study. The tumors were 2 to 18 cm in diameter. FDG uptake at 48 to 60 min after tracer injection was used to determine the standardized uptake value (SUV). The SUVs of the tumor and nontumor regions of the liver were calculated to obtain the tumor-to-nontumor ratio (SUV ratio). The PET results were compared with the findings of CT and histologic examination. RESULTS: The tumors were divided into three types, consisting of those with increased FDG uptake (SUV ratio of 1.07-2.66, Type A, n = 19), similar FDG uptake to the surrounding nontumor region (SUV ratio of 0.77-1.04, Type B, n = 7) and decreased or absent FDG uptake (SUV ratio of 0.13-0.58, Type C, n = 6). In histologic examination, viable HCC tissue remained in all Type A and B tumors, whereas more than 90% necrosis was found in the Type C tumors, indicating that interventional therapy had been effective. These PET findings reflected tumor viability more accurately than the extent of intratumor Lipiodol retention on CT images. CONCLUSION: FDG PET appears to be a valuable method for the assessment of tumor viability after interventional therapy for HCC. PMID- 7989979 TI - Radioimmunoguided surgery using iodine-125-labeled biotinylated monoclonal antibodies and cold avidin. AB - One of the limitations of intraoperative tumor detection with radiolabeled monoclonal antibody (Mab), by means of a gamma-detecting probe (GDP), is the long time interval needed between Mab injection and surgery to obtain low blood-pool activity. Such an interval can be shortened considerably, exploiting the high affinity between avidin and biotin. METHODS: Twenty patients with colorectal cancer were injected with 1 mg of biotinylated 125I monoclonal antibodies followed, 48 hr later, by a chase of cold avidin. During surgery, the GDP was used to detect radioactive emissions from the tumor and normal tissue. Tumor tissue samples were analyzed in vitro by immunohistochemical tests for the presence of tumor antigens and in vivo antibody localization. RESULTS: At the time of surgery (average 7 days postinjection), the mean value of circulating radioactivity was 6% +/- 3% of the injected dose. Of 20 patients studied, tumors were localized in 13 cases (65%). Subclinical tumors were detected in 3 patients (15%). CONCLUSION: The use of 125I-labeled biotinylated Mabs followed by avidin as a chase enhances the applicability and effectiveness of radioimmunoguided surgery technology and will allow the use of radioisotopes with a shorter half life than 125I. PMID- 7989980 TI - Clinical validation of SPECT and CT/MRI image registration in radiolabeled monoclonal antibody studies of colorectal carcinoma. AB - Registration methods combine the anatomic localizing ability of CT or MRI with SPECT images of radiolabeled monoclonal antibodies (Mabs), allowing the accurate staging of patients prior to surgery or following treatment. METHODS: Twenty-four patients (15 males and 9 females, mean age 55 yr, range 29-70 yr) were studied with this technique. Ten patients had suspected colorectal cancer recurrence and were infused with 10 mCi of 131I-CC49 prior to staging laparotomy. Fourteen patients treated in a Phase I radioimmunotherapy study with 131I-CC49 were also studied. All patients underwent SPECT imaging of the abdomen and pelvis 5-7 days following infusion of Mab. RESULTS: Phantom studies demonstrated a 3.6-mm surface fitting mean accuracy of datasets for the liver and 1.8 mm for an intrahepatic tumor. In the presurgical group, SPECT and CT/MRI registration allowed more accurate identification of uptake abnormal sites. Areas of metastatic disease > 1 cm confirmed at surgery were found in six of nine patients with liver lesions and in two patients with extrahepatic (including one patient with pelvic) disease. In patients imaged following radioimmunotherapy, all lesions > 1.5 cm seen on CT/MRI were identified, and activity distribution in tumor and normal tissue could be more accurately assessed. CONCLUSIONS: Routine registration of SPECT and CT/MRI images is feasible and allows more accurate anatomic assessment of sites of abnormal uptake in radiolabeled Mab studies. PMID- 7989982 TI - False-positive reversible perfusion defect during dobutamine-thallium imaging in left bundle branch block. AB - In the presence of pre-existing left bundle branch block (LBBB) exercise stress thallium scans have been associated with false-positive septal and apical perfusion abnormalities. Recent reports have documented a lower incidence of false-positive septal perfusion defects when pharmacologic agents such as dipyridamole or adenosine are utilized in patients with LBBB. Dobutamine, a synthetic catecholamine, is being used with increasing frequency in combination with perfusion agents for the diagnosis of coronary artery disease in patients unable to achieve an adequate exercise workload. Because the positive inotropic and chronotropic actions of doubtamine are similar to the physiologic effects of treadmill exercise, it is conceivable that false-positive perfusion abnormalities will be observed in patients with pre-existing LBBB undergoing dobutamine perfusion imaging. We describe a patient with underlying LBBB who underwent dobutamine thallium imaging which revealed septal and periapical defects. Subsequent coronary angiography showed these abnormalities to be false-positive. It is concluded that septal and periapical perfusion abnormalities during dobutamine thallium imaging may be false-positive and should be interpreted cautiously. PMID- 7989981 TI - Pectus excavatum: abnormal exercise scintigraphy with normal coronary arteries. AB - Pectus excavatum is the most common congenital abnormality of the chest wall, and is frequently associated with chest pain. The invasive, as well as the ECG and echocardiographic assessment of possible coronary artery disease (CAD) in adults with moderate to severe forms of this deformity, is often complicated by the associated displacement of the heart in the chest cavity in these patients. We present findings in a 67-yr-old male that demonstrate that the predictive accuracy of positive stress radionuclide ventriculogram (RVG) and SPECT scintigraphic studies may be significantly reduced in patients with moderate to severe forms of this abnormality. Our findings also suggest, however, that either lateral or even a shallow left posterior oblique detector positioning during RVG, a significantly revised SPECT acquisition orbit, or planar imaging may provide a more accurate means to assess possible CAD in these patients. Like-wise, physician input would appear to be invaluable in determining the optimal mode of imaging and the acquisition protocol for patients with pectus excavatum. PMID- 7989983 TI - Use of bone scintigraphy to select patients with multiple myeloma for treatment with strontium-89. AB - Strontium-89 is an effective agent for palliation of pain due to bony metastases from breast and prostate carcinoma. As a functional analog of calcium, 89Sr is taken up by bone in areas of osteoblastic activity. Since patients with multiple myeloma frequently have osteolytic metastases, 89Sr might not be considered to be a therapeutic option. However, metastases which appear osteolytic by radiographs may demonstrate osteoblastic activity on bone scans. Consequently, the bone scan may be used to identify a subset of patients with osteolytic metastases who may benefit from 89Sr treatment. This report describes a patient with severe rib pain due to multiple myeloma whose chest radiograph showed multiple lucent lesions throughout the bones of the chest wall but whose bone scan showed marked osteoblastic activity. The patient was treated with 89Sr and received substantial pain relief. Bone scans may be useful in selecting myeloma patients or other cancer patients with osteolytic radiographic lesions who may benefit from 89Sr therapy. PMID- 7989984 TI - Enantioselective synthesis of 6-[fluorine-18]-fluoro-L-dopa from no-carrier-added fluorine-18-fluoride. AB - METHODS: A trimethylammonium veratraldehyde triflate was synthesized and used as a precursor for the asymmetric synthesis of 6-[18F]fluoro-L-dopa. RESULTS: Its nucleophilic fluorination with 18F-fluoride produced by the 18O(p,n)18F nuclear reaction on enriched 18O-water led to the corresponding no-carrier-added [18F]fluoroveratraldehyde (45 +/- 5% EOB). Diiodosilane was used to prepare the corresponding [18F]fluorobenzyl iodide (36.5 +/- 5.3% EOB). Akylation of (S)-1 tert-boc-2-tert-butyl-3-methyl-4-imidazolidinone with this electrophilic agent, hydrolysis and purification by preparative high-pressure liquid chromatography made 6-[18F]fluoro-L-dopa ready for human injection, in a 23% +/- 6% decay corrected radiochemical yield. The enantiomeric purity and the specific activity were above 96% and 1 Ci/mumole respectively. CONCLUSION: Through this procedure, starting from 250 mCi of 18F-fluoride, multimillicurie amounts (32 +/- 8.5 mCi) of no-carrier-added 6-[18F]fluoro-L-dopa are now available at the end of synthesis (90 min) with a good radiochemical purity (more than 98%). PMID- 7989985 TI - Consensus development for producing diagnostic procedure guidelines: SPECT brain perfusion imaging with exametazime. AB - A method for developing diagnostic practice guidelines is presented in which a team of experts used a semiquantitative scoring system to reach consensus on a standard procedure for SPECT cerebral perfusion imaging. METHODS: An expert panel generated a list of elements that they thought were important for the optimal performance of cerebral perfusion imaging as the first phase of a modified Delphi panel technique. Panel members then scored each statement to indicate the importance of that statement for the performance of cerebral perfusion imaging. The scores were recorded for each statement and the average score, s.d. and variance for each statement were determined for each successive panel round. A total of three panel rounds were conducted. The change in average s.d. between scoring rounds was analyzed for significance using both parametric and nonparametric tests. RESULTS: The average s.d. decreased by 35% from 2.1 to 1.32 between the first and final panel round. This change in average s.d., which indicated enhanced consensus, was significant at p < 0.0001. Following consensus, all statements were grouped into four categories based on average score: critical elements, important elements, less important elements and elements of uncertain importance. This grouping formed the basis for a guideline summary narrative. Results were generated in 3 mo, at low cost and with clear documentation of rationale. CONCLUSION: Through simple adaptations of this methodology, expert panels that develop practice guidelines can replace informal discussion with systematic scoring methods to rate the quality of evidence, generalizability to practice conditions, appropriate indications and strength of recommendations. PMID- 7989986 TI - An interactive technique for three-dimensional image registration: validation for PET, SPECT, MRI and CT brain studies. AB - A multipurpose three-dimensional registration technique was validated with PET, SPECT, CT and MRI scans, which had been obtained under normal clinical conditions. In contrast to fully automated procedures, this coregistration method is highly interactive, which has the advantage that it does not impose rigid restrictions by data type and by alterations in normal anatomy or brain function resulting from disease. METHODS: Basically, a computer program provides a variety of tools to examine the accuracy of coregistration visually and to specify necessary translations and rotations in all three dimensions. Tools and criteria to accept coregistration were applied according to a standardized protocol. Reproducibility was assessed with five independent users on nine pairs of image sets. In two pairs of these image sets, coregistration was repeated three times by each user. RESULTS: Depending on the resolution of the images involved, the reproducibility of translation distances ranged from 0.32 to 2.22 mm (s.d.) and of rotation angles from 0.32 to 1.70 degrees. It was always much smaller than the point-spread full-width half maximum of the device with the lower resolution. The accuracy of coregistration was examined using two arbitrarily misplaced image sets. Interindividual and intraindividual variance were similar, which suggested that the influence of subjectivity was not significant. Average displacements after coregistration were 0.43 and 0.29 mm or less for PET and MRI data, respectively, which indicated the absence of a systematic bias. CONCLUSION: The results indicate the high reproducibility and accuracy of this three-dimensional coregistration technique, which is comparable or superior to those of automated techniques and methods based on external artificial landmarks. PMID- 7989988 TI - Quantification of the extent and severity of perfusion defects in canine myocardium by PET polar mapping. AB - This study validates perfusion defect extent and severity as derived by PET polar maps in vivo against measurements derived from radiolabeled microspheres. METHODS: In seven open-chest dogs, either the left anterior descending (n = 11) or left circumflex coronary artery (n = 13) were ligated sequentially from distal to proximal. After each occlusion, gated PET images were acquired with 13N ammonia (20 mCi) while radiolabeled microspheres were administered into the left atrium. The transaxial PET images were reoriented into left ventricular short axis cuts, including the apex, and polar maps were generated from circumferential activity profiles. PET polar maps were then compared with polar maps derived from microspheres after normal databases for 13N-ammonia and for microspheres were established. Nitrogen-13 or microsphere activities of less than 1.5 s.d. below the mean were defined as hypoperfused. RESULTS: The extent (percent of left ventricular mass) and mean severity of the hypoperfused myocardium in the postmortem microsphere measurements ranged from 3% to 69% and 3% to 58%, respectively. The estimated extent by summed PET and by microspheres correlated by y = 4.95 + 0.95x (r = 0.91, s.e.e. = 0.085, p < 0.001) and mean severity by y = 5.52 + 0.87x (r = 0.85, s.e.e. = 0.101, p < 0.001). The extent and severity were similar for summed and gated PET studies. CONCLUSION: The current study validated a polar map approach that provides accurate, quantitative assessment of the extent and severity of myocardial perfusion defects in vivo. Gating did not yield an improved correlation between PET and microsphere measurements. Thus, ungated PET images can be used to assess accurately the extent and severity of perfusion defects. PMID- 7989987 TI - Quantitative mapping of regional cerebral blood flow using iodine-123-IMP and SPECT. AB - A method was developed to calculate functional images of regional cerebral blood flow (rCBF) from a single scan using SPECT following intravenous 123I-N-isopropyl p-iodoamphetamine (IMP) infusion. METHODS: A two-compartment model that includes two parameters of rCBF and regional distribution volume of IMP (Vd) was employed to correct for clearance of IMP from the brain. Using a given input function and a fixed Vd value (30 ml/ml according to an analysis on dynamic SPECT data), a unique value of rCBF was calculated for each pixel of the SPECT image according to the table-look-up procedure. This technique was applied to 15 human subjects, and the calculated rCBF values were compared with those measured by PET. RESULTS: A set of simulation studies demonstrated an optimal SPECT midscan time at 30 to 40 min postinjection of IMP, providing the minimal error sensitivity to the individual difference of the input function (rCBF values with an accuracy of +/- 10%). Another set of simulation suggested validity of fixing the Vd values, i.e., errors in calculated rCBF values were around +/- 7% for a change of Vd of +/- 10%. The measured rCBF values obtained from 15 human subjects were independent on the SPECT scan time. The calculated rCBF values also agreed well with those obtained by the nonlinear least-squares fitting analysis that were obtained from the dynamic SPECT scan and the frequent arterial blood sampling and measurement of lipophilic fraction for each sample (0.54 + 0.88x, r = 0.86), suggesting the validity of the simplified procedures in this method. CONCLUSION: These observations suggested the validity of this method as a clinical tool for quantitative measurement of rCBF. PMID- 7989990 TI - Artificial neural networks: better than the real thing? PMID- 7989989 TI - Automated interpretation of planar thallium-201-dipyridamole stress redistribution scintigrams using artificial neural networks. AB - To develop an automated image interpretation system of planar cardiac 201Tl dipyridamole stress/redistribution scintigrams, the authors used artificial neural networks that associate patterns of segmental myocardial thallium uptake with a diagnostic assessment about the presence, severity and localization of significant coronary artery disease. METHODS: Artificial neural networks were trained and evaluated using the results from segmental thallium analysis and either expert readings in 159 cases or coronary angiography in a subgroup of 81 patients. RESULTS: Based on receiver operating characteristics analysis, the sensitivity for the detection of significant coronary artery disease at a specificity of 90% was 51% compared with angiography and 72% compared with the human expert. For severity and localization of disease, two vascular territories assigned to the vascular bed of the left anterior descending (LAD) artery and to the territory subtended by the left circumflex artery and the right coronary artery together (CX/RCA) were included in the analysis. CONCLUSION: Artificial neural networks may be useful to develop automated computer-based image interpretation systems of 201Tl perfusion scintigrams. However, utilization of large training datasets appears to be a prerequisite to achieve adequate diagnostic performance. PMID- 7989992 TI - Formulas to estimate renal depth in adults. PMID- 7989991 TI - Iodine-131 therapy of thyroid cancer: extensive contamination of the hospital room in a patient with tracheostomy. PMID- 7989993 TI - Combined intravenous dipyridamole and symptom-related stress testing. PMID- 7989994 TI - Technetium-99m-sestamibi imaging in breast cancer: an alternative to thallium-201 imaging. PMID- 7989995 TI - Clinical utility of bone scan features of pleural effusion: sensitivity and specificity for malignancy based on pleural fluid cytopathology. PMID- 7989997 TI - The permanent whitewater. PMID- 7989996 TI - False-positive radioiodine uptake in lung carcinoma. PMID- 7989998 TI - Integrating nursing research findings into the curriculum: a descriptive study. AB - This descriptive study examined methods used to integrate nursing research findings into associate, baccalaureate, and master's nursing program curricula. Nursing faculty members (N = 420) from 105 programs in the NLN's North Atlantic region were asked, in a mailed survey, to indicate the course objectives and learning activities concerning nursing research findings used in their courses. Completed surveys were returned from 55% (n = 231). Chi-square analyses showed significant differences in all course objectives and most learning activities among faculty. Faculty in baccalaureate and/or master's programs used the objectives and most learning activities concerning nursing research findings more than faculty from the associate degree programs. Overall, however, faculty have made concerted efforts to each nursing research findings using a variety of course objectives and learning activities. Further research is recommended to determine the most effective strategies. Educators are encouraged to provide opportunities for students to use accepted research findings in practice. PMID- 7989999 TI - Computer-assisted instruction: a learner's viewpoint. AB - Computer-assisted instruction (CAI) is becoming increasingly common in nursing. Insight into factors that facilitate or impede this process was gained through interviews with nursing students who had used one of four computer programs. Content analysis of these interviews found that the CAI experience includes many components. Three overall categories of comments emerged, pertaining to (a) the learner, (b) the learning environment, and (c) software design, including interactive features, how the learning design uses these features to achieve the learning objectives, and the content. This paper discusses elements that facilitate or hinder learning in each area and illustrates each with quotes from the interviews. This article also suggests positive actions that can increase learning through CAI use. PMID- 7990000 TI - Clinical teaching effectiveness described in relation to learning outcomes of baccalaureate nursing students. AB - Grounded in cumulative findings on teaching effectiveness from K-12 education, higher education, and professional education, this process-product study empirically explored the relationship between 24 specific teacher behaviors generally thought to be effective for student learning and learning outcomes of baccalaureate nursing students. Two measures of learning in a critical care practicum taught by staff nurse preceptors were used: performance in the practicum as assessed on a clinical evaluation instrument developed by faculty, and performance on a standardized test of knowledge in critical care. Important aspects of clinical teaching effectiveness included the ability to set clear objectives to help students organize their learning, to ask appropriate questions, to provide specific and timely feedback to students, and to convey a positive, concerned attitude. Certain teaching behaviors showed significant relationships with cognitive learning outcomes, while others were tied to performance outcomes. PMID- 7990002 TI - Statistical consultation: what should a client know? PMID- 7990001 TI - The self-concepts and motivational orientations of registered nurse master's degree students. AB - The results of this investigation indicate that nurses enrolling in nursing master's degree programs are motivated to do so for reasons related to professional achievement and increasing their knowledge base. Many of the respondents indicated the desire to seek positions that reflect the more advanced practice roles in nursing, such as clinical nurse specialist, nurse practitioner, or nurse educator, upon completion of the degree. This is significant when considering that the investigation was conducted during a serious nursing shortage when much emphasis was placed on the recruitment and retention of staff nurses to work at the bedside (Fenner, 1987). The results of this investigation have implications for nursing educators and program administrators in master's degree programs. The seven motivational orientations underlying the reasons for returning to school should be considered when evaluating the ability of their programs to meet the needs and goals of their applicants. This might be accomplished by the exploration of the applicants' reasons for returning to school as well as their professional goals upon completion of the degree during the application process. An exit interview done on completion of the degree requirements could also be performed to determine if the program met the needs of the student. PMID- 7990003 TI - Effects of BSN student preferences for studying alone or in groups on performance and attitude when using interactive videodisc instruction. PMID- 7990004 TI - Live supervision: developing therapeutic competence in family systems nursing. PMID- 7990005 TI - Teaching graduate students to write for publication. PMID- 7990006 TI - Defending the master's thesis in nursing graduate programs: the Canadian context. PMID- 7990007 TI - Patho-flow diagramming: a strategy for critical thinking and clinical decision making. AB - Developing and implementing alternative strategies to assist nursing students to gain critical thinking and clinical decision-making skills are paramount for today's nurse educator. Patho-flow diagramming is offered as a strategy that merges nursing process and pathophysiology with approaches used effectively in general education to develop thinking skills. PMID- 7990008 TI - Celebrating the international year of the midwife. PMID- 7990009 TI - Barriers to breast cancer screening in older women. A review. AB - As health care reform unfolds over the next several years, nurse-midwives will be increasingly addressing issues of health care in women of all ages across the life span. For older women, a prevalent condition that has received minimal attention in this age group has been breast cancer. Distinctions have been noted in the literature between older and younger women in terms of the biology, screening, and treatment of breast cancer. Despite theories that breast tumors in older individuals are more indolent and slower growing than those found in younger women, older women's mortality from breast cancer is higher. Although part of this is theorized to be due to other biologic processes, such as increased immune suppression with aging, it appears that most of the distinction between the courses of breast cancer in older and younger individuals has been related to decreased screening during advanced age. This manuscript describes the individual client, health care provider, and health care system barriers to each of the three major elements of breast cancer screening--breast self-examination, clinical breast examination, and mammography. Suggestions and caveats including ethical, legal, and political issues regarding breast cancer screening in older women are presented. PMID- 7990010 TI - Nurse midwives' attitudes toward abortion performance and related procedures. AB - In 1990 a symposium was held by the American College of Obstetricians and Gynecologists and the National Abortion Federation to address the national shortage of physician abortion providers. One symposium recommendation was that nurse-midwives be trained to perform first-trimester legal abortions under physician supervision. A national mail survey was conducted to determine the attitudes of nurse-midwives toward performing abortion and related procedures. One-half of the nurse-midwives who were members of the American College of Nurse Midwives as of October 1991 were polled, and 1,208 questionnaires (71.1%) were returned, resulting in a sample representative of the general membership and students. Seventy-nine percent of respondents would not support federal and state efforts to limit access to abortion, 52% would or possibly would vote in a secret ballot to permit the performance of abortion by certified nurse-midwives; 24% would, or possibly would, incorporate abortion procedures into their practice; and 19% would, or possibly would, perform abortions in an abortion clinic. The lowest level of support to permit the certified nurse-midwife practice of abortion came from the midwest (31%) and southeast (41%) and the greatest from the west coast (65%). Supporters for the nurse-midwife performance of abortion were more likely to have practiced well-woman gynecology and provided abortion related services such as abortion referrals, pre- and postabortion workups and the treatment of abortion-related complications. They were more likely to have inserted intrauterine contraceptive devices and laminaria, and to have performed circumcision. Opinions about the performance of abortion were not related to age, education, or student status. The majority of nurse-midwives (91%) would be willing to refer a woman to another provider for an abortion, prescribe RU 486 (57%), and perform dilation and curettage for spontaneous abortion (56%). The American College of Nurse-Midwives membership reported many different reasons for support of and opposition to professional involvement with abortion. Further research suggestions for institutional policy and individual practice are offered. PMID- 7990011 TI - Modifying a childbirth education curriculum for two specific populations. Inner city adolescents and substance-using women. AB - An interdisciplinary care provider team conducted a nonexperimental, observational, descriptive study to determine a childbirth education curriculum that would meet the needs of pregnant adolescent and substance-using women who attend prenatal clinics at an urban, municipal hospital center. A childbirth education curriculum, originally taught to a clinic population in 1974, was used with the two special populations in 1993 for a 7-month period. Participants were encouraged to provide feedback about the curriculum for each class by offering suggestions for additions or deletions of content. Provider staff also evaluated the content for applicability today. At the end of the study period, the pregnant adolescent group had been most involved with the class exercises; members of the group provided feedback about content. They were consistently positive in evaluating the entire six-class curriculum and recommended some additional topics. The adolescents demonstrated sustained interest in breast-feeding. The substance-using women, on the other hand, expressed a preference for content that focused on labor and birth; they preferred to ask questions, individually and in the privacy of the examining room, and showed negligible interest in breast feeding. PMID- 7990013 TI - The International Confederation of Midwives. Past history, present activities, and future challenges. AB - The International Confederation of Midwives is celebrating its 75th anniversary in 1994. The Confederation is composed of 61 member associations from 50 countries and thus includes more than 100,000 midwives. Its aims are to advance midwifery education and the role of the professional midwife, to improve the standard of maternal and child health care, and to support and advise associations of midwives in liaison with their governments. This article reviews the history and current activities of the Confederation, and discusses future challenges and new directions for the organization. PMID- 7990012 TI - Teaching strategies for preceptors of beginning intrapartal students. AB - This article describes a variety of ways to help novice students learn the nurse midwifery skills required when caring for laboring women. The influences of learning style, undergraduate nursing experience, and previous work settings are discussed. The art of nurse-midwifery is emphasized, and ways to encourage and support students are discussed. PMID- 7990014 TI - Strategies for dissemination of policy research. AB - Although there is evidence of high-quality care and cost-effective practice by certified nurse-midwives, CNMs still face many barriers to practice. Outcomes must be documented and disseminated more widely so that policy makers will be convinced that restrictions to CNM practice must be removed. The author identifies three obstacles to policy-related research dissemination: lack of cumulative data, lack of relevance to specific issues, and lack of power. To overcome these obstacles, five strategies are proposed to promote a wider dissemination of policy-related research results. CNMs must use these strategies to promote nurse-midwifery to the general public, government officials, interest groups, and policy makers. PMID- 7990015 TI - Gingival cell IL-2 and IL-4 in early-onset periodontitis. AB - The purpose of this study was to compare, using cell blot analysis, the association of gingival tissue mononuclear cells (GTMC) isolated from lesions displaying histories of early-onset periodontitis (EOP; typically B-lymphocyte dominated) and gingivitis (typically T-lymphocyte dominated) with the B-cell stimulating cytokine, interleukin (IL)-4, and the T-cell stimulating cytokine, IL 2. Eleven EOP patients and 11 age- and gender-similar gingivitis control (GC) subjects participated. Gingival tissue adjacent to the alveolar crest normally removed during surgery was digested in collagenase-containing media and GTMC were isolated by density gradient centrifugation. Cells were separated into four aliquots. One was left unstimulated; the remainder were stimulated for 2 hours with Porphyromonas gingivalis outer membrane protein, mitogen Concanavalin A, or common antigen tetanus toxoid. Cells then were centrifuged onto transfer membranes and incubated in RPMI 1640 media for 6 hours to allow absorption of secreted cytokine. Membranes were treated with monoclonal anti-IL-2 or anti-IL-4, followed by a biotin-conjugated second layer, streptavidin-alkaline phosphatase and nitro blue tetrazolium/5-bromo-4-chloro-indolyl-phosphate (NBT/BCIP) color development. A higher percentage of GTMC from EOP patients were IL-2+ when stimulated with P. gingivalis compared with GTMC from GC patients (20 +/- 2% vs. 12 +/- 2%, P < 0.003). A higher percentage of non-stimulated GTMC from EOP patients produced IL-4 than from GC (22 +/- 4% vs. 6 +/- 3%, P < 0.00007), as well as when stimulated with P. gingivalis (22 +/- 3% vs. 13 +/- 2%, P < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7990016 TI - Incidence of early periodontitis in a group of young individuals during 8 years: associations with selected potential predictors. AB - The aim of the present study was to assess the incidence of early radiographic bone loss in a birth cohort over 8 years and to assess possible associations between incidence of bone loss and reported dental behavior, ethnic background, and previous orthodontic treatment. In a case control study comprising a proportion of the study population, the detection of black pigmented Bacteroides and Actinobacillus actinomycetemcomitans and their association with early radiographic bone loss was assessed. At the beginning of the study in 1984, there were 2,767 subjects. In 1992 sets of bite-wing radiographs were obtained from 215 subjects, who also filled out a questionnaire concerning their present and past dental behavior, ethnic background, and orthodontic treatment. Radiographic alveolar bone loss was recorded if the distance from the cemento-enamel junction to the alveolar crest exceeded 2 mm. Thirteen subjects (6%) showed new sites with bone loss over the 8-year period. Subgingival plaque was sampled from these 13 subjects and from 13 control subjects. None of the independent variables could be associated with the observed incidence of radiographic bone loss in this cohort, with the possible exception of the presence of A. actinomycetemcomitans which was detected in about 50% of the new sites with bone loss. PMID- 7990017 TI - Actinobacillus actinomycetemcomitans in adult periodontitis. I. Topographic distribution before and after treatment. AB - The aim of this investigation was to study the topographic distribution of Actinobacillus actinomycetemcomitans in patients with adult periodontitis before and after mechanical periodontal treatment (repeated oral hygiene instructions, systematic deep scaling, and root planing). In 10 A. actinomycetemcomitans positive patients, subgingival microbial samples were obtained from the mesial and distal aspect of every tooth (38 to 56 sites per patient, 479 sites in total) before and one month after treatment. The samples were cultured on TSBV agar. A. actinomycetemcomitans was identified based on phenotypical and serological criteria. A. actinomycetemcomitans was present in 40% of the samples taken before and in 23% of the samples taken after treatment. Before treatment, the frequency of A. actinomycetemcomitans-positive samples per patient was wide spread and ranged from 7 to 90%. After treatment, two patterns of A. actinomycetemcomitans distribution could be recognized: the majority of the patients showed only a limited percentage of positive samples and yielded less than 10(5) A. actinomycetemcomitans. In three subjects, however, relatively high numbers of positive sites were still present, and many of these positive sites showed high A. actinomycetemcomitans counts. Logistic multiple regression showed the presence of A. actinomycetemcomitans before treatment depended strongly on the individual and was significantly associated with probing depth (P < 0.001) and bleeding upon sampling (P = 0.07). The highest chance of detecting A. actinomycetemcomitans existed in deep pockets which bled upon sampling. After treatment, there was a strong individual influence and an influence of probing depth (P < 0.001). The highest chance of detecting A. actinomycetemcomitans existed in residual pockets in the range of 5 mm. PMID- 7990018 TI - Actinobacillus actinomycetemcomitans in adult periodontitis. II. Characterization of isolated strains and effect of mechanical periodontal treatment. AB - Ten systemically healthy subjects (ages 28 to 60 years) with untreated moderate to severe periodontal disease and evidence of presence of A. actinomycetemcomitans underwent standard mechanical periodontal treatment consisting of oral hygiene instruction and systematic deep scaling and root planing. Before, and 4 to 5 weeks after treatment, clinical measurements and separate subgingival microbiological samples were taken from the mesial and distal aspect of every tooth, with the exception of the third molars. A. actinomycetemcomitans could still be detected in all patients after treatment. In 9 of the 10 patients, all tested isolates from both examinations were of a single type. Two patients carried serotype a; 2 serotype b; 2 serotype c; and 1 serotype e. Two individuals showed only non-typeable isolates lacking serotype a, b, c, d, or e specific antigens. Another subject was colonized by serotype c and, in addition, yielded a non-typeable isolate. Persistence of A. actinomycetemcomitans after treatment was significantly correlated with the frequency of A. actinomycetemcomitans before treatment (P < 0.001) and the mean probing depth before treatment (P < 0.05). No serotype-specific patterns of treatment outcome could be recognized. The analysis of the site specific effect of treatment showed a significant relationship between post treatment levels of A. actinomycetemcomitans and both probing depth reduction as well as attachment gain. Individuals showing evidence of A. actinomycetemcomitans in a multitude of sites appeared to be more difficult to treat than patients with few positive sites only. Within such individuals, the deeper pockets showed the greater resistance to eradication of A. actinomycetemcomitans. PMID- 7990019 TI - Locally delivered minocycline and guided tissue regeneration to treat post juvenile periodontitis. A case report. AB - A case of post-juvenile periodontitis in a 28-year-old female patient is described along with new periodontal treatment modalities. Administration of minocycline-HCl with local drug delivery system was introduced as a part of initial periodontal therapy following microbiological and immunological examinations. The lesions were subsequently treated by guided tissue regeneration, which resulted in considerable gain of attachment with minimal recession of marginal gingiva. This observation suggests that the local delivery of antibiotics and regenerative therapy may prove to be effective alternative modalities in treatment of post-juvenile periodontitis. PMID- 7990020 TI - Effects of tetracycline-containing gel and a mixture of tetracycline and citric acid-containing gel on non-surgical periodontal therapy. AB - The purpose of this study was to assess the clinical and microbiological effects of a newly developed root conditioning gel system containing tetracycline or a mixture of tetracycline and citric acid on non-surgical periodontal therapy. Sixty-four (64) single-rooted teeth with a probing depth of 4 to 6 mm were randomly subjected to one of the following four treatments; 1) root planing alone (RP group); 2) tetracycline-containing gel alone (TCG group); 3) root planing plus tetracycline-containing gel (RP + TCG group); or 4) root planing plus a mixture of tetracycline and citric acid-containing gel (RP + TC-CAG group). Probing depth, attachment level, and tooth mobility were measured and the presence of dental plaque and gingival inflammation was recorded at baseline and after 2, 4, 8, and 12 weeks. Subgingival plaque samples from each site were collected at the same visits and examined with phase contrast microscopy for proportions of motile rods and spirochetes. Plaque index, gingival sulcus bleeding index (SBI), probing depth, and attachment level decreased significantly in all groups compared to the baseline values (P < 0.05). A significant decrease in probing pocket depth was noted after 12 weeks in RP + TC-CAG group compared to the other groups (P < 0.05). Significantly more gain in attachment was detected in the RP + TC-CAG group compared to the TCG group (P < 0.05). Tooth mobility scores also decreased later in the study. A significant decrease in the proportion of motile rods was found primarily in the RP + TC-CAG group.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7990022 TI - The effect of post-surgical flap placement on probing depth and attachment level: a 2-year longitudinal study. AB - Postsurgical flap placement might affect the outcome of the operative procedure. Modified Widman flap surgery with primary closure and flap approximation (usually away from the bone crest) and apically positioned flap surgery with near crestal bone positioning are both widely used in surgical periodontal treatment. Several comparative investigations have studied these modalities, however, none have been able to show conclusively that either is superior to the other. The purpose of this longitudinal study was to explore the optimal postsurgical flap placement in respect to final probing depth and changes in clinical attachment level. Following routine hygienic phase of treatment, 12 subjects (186 teeth) with adult periodontitis received surgical periodontal treatment. Prior to the flap surgery, probing depth and clinical attachment level were recorded. Sounding depth measurements were taken to record postoperative flap placement. Patients were placed on a 3-month maintenance program. Probing depth and clinical attachment level were again measured at 2 years postoperatively and compared to baseline measurements. An overall positive correlation (R = 0.43; P = 0.0248) was found between immediate postoperative sounding measurements and probing depth after 2 years. Conversely, attachment level changes over the 2-year period showed only weak inverse correlation (R = 0.27; P = 0.0121) with sounding depth measurement immediately postsurgically. Sites where postoperative sounding depth were < or = 3 mm had a mean probing depth (2.52 mm) which was significantly (P < 0.001) smaller compared to sites with sound depth > or = 4 mm (3.58 mm). Changes in clinical attachment level varied between sites and sounding depth groups; however, none of these differences were statistically significant. Based on our findings it is suggested that following periodontal flap surgery, in those cases where minimal probing depth is desired, the flap be secured to the underlying structures at or slightly coronally to the bone crest (< or = 3 mm).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7990021 TI - The influence of supragingival plaque control on clinical and microbial outcomes following the use of antibiotics for the treatment of periodontitis. AB - Although supragingival plaque control is essential to successful periodontal therapy, the role of plaque control following systemic antibiotic use in periodontal disease has not been well defined. This study evaluated, following antibiotic use, which clinical and microbial parameters appeared to be influenced primarily by the antibiotics, independent of plaque control, and which outcomes appeared to be dependent on plaque control. Two hundred thirty-six patients (236) with moderate to severe periodontitis were clinically evaluated and microbial samples were taken by their private-practice periodontists. All patients were treated with scaling and root planing and a variety of systemic antibiotics, which were selected based on the microbial and clinical profile of the patient. Three months after therapy, patients were reevaluated and grouped by post treatment plaque control, as either having very good oral hygiene (LoPl: N = 143; < or = 10% plaque-covered surfaces) or poor oral hygiene (HiPl: N = 93; > or = 25% plaque-covered surfaces). The two groups had different plaque and bleeding scores initially, but similar numbers of pockets probing > 5 mm and similar microbial patterns. Although the LoPl group had a significantly greater reduction in plaque than the HiPl group, bleeding scores and probing depths changed comparably in both groups after antibiotic therapy. Plaque control influenced outcomes significantly, but in a complex manner. The LoPl group exhibited a significantly greater reduction in certain bacteria, for example P. gingivalis. Interactions between plaque control and specific microbial parameters significantly affected clinical outcomes, although neither alone was sufficient to predict outcomes following antibiotic therapy.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7990023 TI - Root grooves: a risk factor in periodontal attachment loss. AB - Periodontal health reflects a balance between harmful and protective elements in the gingival margin area. The total plaque mass, specific periodontopathogens, and local environmental factors may challenge this balance. The aim of this retrospective study was to evaluate the effect of proximal root grooves as a risk factor in periodontal attachment loss. One-hundred and three (103) extracted, formalin-stored, single-rooted teeth showing loss of attachment and having one non-grooved and one grooved proximal root surface were selected for the study. Following staining in 0.1% toluidine blue to visualize attached periodontal ligament remnants, the teeth were examined in a light microscope under incident light. On each tooth, loss of attachment was measured along the long axis of the root from the cemento-enamel junction to the most coronal level of the stained periodontal ligament remnants on mesial as well as on distal surfaces. Incisors and premolars were grouped separately. For both groups, a statistically significant greater loss of attachment was present on grooved than on non-grooved surfaces (P < 0.0001). Generally, there was a direct relationship between groove location and maximum loss of attachment. The results indicate that proximal root grooves should be considered in periodontal diagnosis, prognosis, and treatment planning. PMID- 7990024 TI - Gingival recession: intra-oral distribution and associated factors. AB - This study assesses the role of poor oral hygiene and forceful toothbrushing as risk factors for recession. As part of a cross-sectional root surface caries study, 298 subjects, 42 to 67 years of age, with at least one exposed root surface, were examined. Since 66% of the root surface exposure and practically all the abrasion was on buccal surfaces, the analyses focused only on the buccal surface. Analysis of variance on subject means for buccal recession showed both calculus and presence of buccal root surfaces with abrasion to be significantly associated with recession after adjusting for age and gender. Root surface abrasion was considered a surrogate variable for forceful brushing. An additional analysis utilized means for each tooth, aggregating across subjects. For each of the 32 tooth types mean buccal recession, percent of exposed root surfaces with abrasion (%ra), and mean debris and calculus scores were calculated. Partial correlation coefficients across tooth types between recession and calculus, adjusting for abrasion, and for recession and abrasion adjusting for calculus, were 0.55. Interpretation of the %ra as a crude measure of forceful brushing is supported by its strong negative correlation across tooth types, with mean debris (r = -0.8) and mean calculus (r = -0.7). Separate analyses on premolars and on molars suggested that recession on premolars may be primarily due to brushing force and on the molars may be primarily due to debris and calculus. The findings suggest that recession is positively associated with percent abrasion (reflecting forceful brushing) and with poor oral hygiene. PMID- 7990025 TI - Evaluation of the effects of diagnostic radiation on titanium dental implant osseointegration in the micropig. AB - The effect that diagnostic radiation may have on peri-implant supporting alveolar tissues is not well understood. Fifty-four (54) titanium dental implants were inserted into the posterior mandible of nine micropigs. At implant placement surgery, 18 implants were exposed to either 2 (diagnostic) or 10 (excessive) doses of diagnostic radiation; the remaining 36 implants served as controls. Fourteen weeks after implant placement, standardized clinical radiographs were taken, pigs were euthanized, and implants with supporting alveolar tissues were prepared and examined by light and scanning electron microscopy (SEM). Ninety seven sections were evaluated by SEM for morphometric and morphologic analyses. The mean percent of implant length in contact with bone was 47% for the controls and 53% for the implants receiving radiation. Five implants were lost during the initial healing phase and four implants were clinically mobile at time of euthanasia, giving a success rate of 83% (45/54). Correlative light microscopy of peri-implant supporting tissues revealed no distinct differences between the microvasculature of controls versus implants exposed to radiation. Standardized clinical radiographs revealed crestal saucerization in both control and radiated implants. This study revealed no statistically significant difference for the percent of implant length in contact with alveolar bone for controls or implants exposed to 2 or 10 doses of diagnostic radiation at implant placement time. PMID- 7990027 TI - Actinobacillus actinomycetemcomitans in adult periodontitis. PMID- 7990026 TI - Bone grafting and guided bone regeneration for immediate dental implants in humans. AB - This study evaluated bone regeneration and osseointegration of hydroxyapatite (HA) coated and titanium plasma sprayed (TPS) implants placed in sockets immediately after extraction in 36 adults, mean age 55.2 years (range 26 to 81 years). Twelve TPS and 10 HA-coated implants in 20 patients were grafted with demineralized freeze-dried bone allograft (DFDBA), covered with a barrier material, and the facial flap coronally positioned to attain primary closure (experimental). The remaining 11 TPS and 10 HA-coated implants were placed similarly, except that no DFDBA was used (control). Osseous structures were measured at the initial placement and 6-month re-entry surgeries. At the 6-month re-entry, all implants placed were clinically osseointegrated. Bone resorption at the most coronal socket crest was -1.53 mm for the grafted group and -1.59 mm for the control group. Crestal bone apposition of 1.39 mm was noted at the most apical socket crest (ASC) for the grafted group, whereas crestal resorption of 0.11 mm was noted in the ungrafted control group (P < 0.02). Bone fill from the base of the deepest osseous defect was 5.68 mm for the grafted group and 3.18 mm for the control group (P < 0.04). Complete resolution of osseous defects occurred at 15 of 22 sites in the grafted group and at 9 of 21 sites in the control group. Clinical exposure of the barrier material and a subsequent inflammatory response at 27 of 43 sites, requires removal of the material prior to the 6-month re-entry and was associated with significantly more bone loss at the ASC sites (P < 0.01). There was no significant difference for any of the parameters when comparing the TPS with the HA-coated implants. PMID- 7990028 TI - Constitutive upregulation of calcium channel currents in rat phaeochromocytoma cells: role of c-fos and c-jun. AB - 1. Northern blot analysis and cell transfection were used in conjunction with whole-cell current recordings to examine the involvement of the immediate early genes, c-fos and c-jun, in the expression of calcium channel currents. 2. Phaeochromocytoma cells (PC12 clone) were exposed to nerve growth factor (NGF) and to depolarizing concentrations of KCl for 60 min every day. Cells challenged with NGF developed extensive networks of neurites within 3 days. Cells depolarized periodically retained their undifferentiated morphology even after 5 days of treatment. 3. The maximal amplitude of high-voltage-activated calcium currents (ICa) increased from the control level of 117.8 +/- 48.3 (mean +/- S.D.) to 387.2 +/- 90.1 pA within 3 days of NGF treatment. omega-Conotoxin (5-10 microM) inhibited 24.6 +/- 8.5% of ICa in undifferentiated cells and 57.8 +/- 6.9% in NGF-treated cells. 4. The levels of c-fos and c-jun mRNAs increased transiently during each daily exposure to NGF. The level of c-fos mRNA also increased transiently during repeated KCl-induced depolarizations but c-jun mRNA remained low or absent. 5. Naive PC12 cells were transiently co-transfected with expression plasmids that contained the full length of c-fos and c-jun cDNA. After 2 days following transfection, the PC12 cells could be grouped according to the size of ICa. In 56% of cells, ICa was similar to control currents (106.1 +/- 37.4 pA). In the remaining 44% of cells, ICa showed a 2.2-fold enhancement with respect to control cells. Transfection of only c-fos had no effect on ICa but, in 24% of cells transfected with c-jun, ICa was 176.6 +/- 124.6 pA. Since periodic membrane depolarization induced c-fos but not c-jun mRNA, c-jun transfection was combined with a high-K+ treatment over 3 days. In 18% of treated cells, ICa was 3.7 times larger than control currents. Morphological differentiation was not observed in transfected cells. 6. In PC12 cells co-transfected with c-fos and c jun or treated with high K+ after transfection of c-jun, omega-conotoxin (5-10 microM) inhibited 68.7 +/- 11.9% of ICa when the current amplitude was in the range of 200-600 pA. since similar concentrations of omega-conotoxin blocked 19.2 +/- 5.4% of ICa in control cells, the current increase induced by c-fos and c-jun was supported by up to 11-fold enhancement of the omega-conotoxin-sensitive component of ICa.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 7990029 TI - The roles of K+ conductance in expiratory pattern generation in anaesthetized cats. AB - 1. The potassium current blockers caesium and tetraethylammonium were injected intracellularly by ionophoretic current into brainstem expiratory neurones of the ventral group. Neurones were identified by their spontaneous activity and by antidromic excitation from the spinal cord at the C2-C3 level. 2. The duration of action potentials increased and the early and late after-hyperpolarizations were completely suppressed. These effects on action potentials were reversible, recovered with an exponential time course within 3 min, and could be reproduced when blockers were applied repetitively into the same neurone. They were ascribed to blockade of potassium channels in the somatic membrane region. 3. Potassium channel blockers modified postsynaptic potentials: early-inspiratory hyperpolarizations were reversibly depressed while postinspiratory and expiratory depolarizations were irreversibly enhanced. The former effect was associated with a decrease of the neuronal input conductance. The latter effect was cumulative upon repetitive ionophoretic applications of potassium blockers. 4. The results demonstrate that potassium currents exert two different roles in expiratory pattern generation. Together with chloride currents, they contribute to the phasic early-inspiratory inhibition. They seem to be calcium-dependent and GABAB receptor-controlled currents which predominate near to the cell body. 5. Potassium currents also operate throughout the postinspiratory and late expiratory periods. They seem to include persistent potassium currents which modulate the excitatory respiratory drive provided by the respiratory rhythm generator. We assume that these currents, widely distributed over the somatodendritic membrane area, are a target for neuromodulation by transmitters and intracellular second messengers. PMID- 7990030 TI - Exercise-induced changes in plasma potassium and the ventilatory threshold in man. AB - 1. It has been reported that, during incremental exercise testing, the patterns of change in ventilation (VE) and arterial K+ (Ka+) are similar, suggesting that changing Ka+ may lead to the phenomenon of the ventilatory threshold through its action on the peripheral chemoreceptors. 2. Expiratory ventilation, oxygen consumption, CO2 production (VE, VO2, VCO2), arterialized venous PCO2 (Pav, CO2; see Methods), pH (pHav), K+ (Kav+) and lactate were measured during incremental exercise tests undertaken by six normal male subjects under control conditions and during lactic acidosis following severe exercise (experimental trial). 3. A ventilatory threshold, associated with a period of isocapnic buffering, was observed under both control and experimental conditions. During the control trial, plots of Kav+ against VO2 showed an inflexion close to the ventilatory threshold. Throughout the experimental trial Kav+ rose linearly relative to VO2. In both control and experimental trials Kav+ concentrations were similar at the ventilatory threshold. 4. These results suggest that the pattern of change of Ka+ cannot account for the phenomenon of the ventilatory threshold. The possibility that the peripheral chemoreceptor response is non-linear above a critical value of Ka+ requires further investigation. PMID- 7990031 TI - Intercostal muscle compensation for parasternal paralysis in the dog: central and proprioceptive mechanisms. AB - 1. Denervation of the parasternal intercostal muscles in the dog is known to cause a substantial reduction in the inspiratory cranial displacement of the ribs and a compensatory increase in the activation of the other inspiratory intercostal muscles, namely the external intercostals and the levator costae. The present studies were designed to assess the mechanism(s) of that compensation. 2. Denervating the parasternal intercostals bilaterally caused a reduction in tidal volume and an increase in arterial PCO2 (Pa, CO2). Severing the parasternal intercostals selectively produced similar changes. The concomitant increases in external intercostal and levator costae activity, however, were much greater than predicted on the basis of the increased Pa, CO2. 3. Denervating the parasternal intercostals on one side of the chest produced large increases in ipsilateral, but not contralateral external intercostal activity. 4. Manipulating the ribs after the parasternal intercostals were inactivated so as to reproduce the normal inspiratory cranial displacement of the ribs elicited immediate, clear-cut reductions in external intercostal and levator costae activities. 5. The increases in external intercostal and levator costae activities that occur after inactivation of the parasternal intercostals thus result partly from the increased hypercapnic drive but mostly from proprioceptive reflexes, presumably muscle spindle reflexes. PMID- 7990032 TI - Neurally maintained hypersecretion in undernourished rat intestine activated by E. coli STa enterotoxin and cyclic nucleotides in vitro. AB - 1. The electrogenic secretory responses of stripped jejuna and ilea from chronically undernourished rats (50% control diet for 21 days) to the bacterial enterotoxin Escherichia coli STa, measured as the short-circuit current in vitro, show an enhanced maximum secretion (ISC, max) with a prolonged duration compared with fed intestine. 2. The ISC, max is unaffected by pretreatment of the intestine in vitro with hexamethonium, atropine, procaine or indomethacin, or by desensitization to 5-hydroxytryptamine (5-HT), while the prolonged duration is unaffected by atropine, indomethacin or 5-HT desensitization but is reduced by hexamethonium and procaine. 3. Both 8-bromo-cyclic GMP and dibutyryl cyclic AMP added serosally activate the enhanced ISC, max and its maintenance. Pretreatment with tetrodotoxin had no effect on the initial ISC, max but prevented its maintenance. 4. Bethanechol, dimethyl phenyl piperazinium, vasoactive intestinal polypeptide, 5-HT and luminal propionate all induced the characteristic hypersecretory activity in the undernourished intestine compared with the fed state, but none could activate the maintenance circuit to prolong their transient responses. 5. Maintenance of the induced hypersecretory activity is the first example of induction of the neural control of intestinal secretion by the dietary intake level and illustrates the plasticity of the enteric nervous system. PMID- 7990033 TI - Effects of palmitoyl carnitine and related metabolites on the avian Ca(2+)-ATPase and Ca2+ release channel. AB - 1. In birds, prolonged cold exposure induces the development of a non-shivering thermogenesis (NST) of muscular origin that may result from an increase in ATP dependent cycling of Ca2+ between the sarcoplasmic reticulum (SR) and the cytosol. 2. Because fatty acids are thought to play a significant role in NST, we investigated the effects of palmitic acid and related metabolites on skeletal SR Ca2+ uptake and release in ducklings. 3. Ca(2+)-ATPase activity, 45Ca2+ release and [3H]ryanodine-binding measurements indicated that palmitic acid was without effect on the Ca(2+)-ATPase and Ca2+ release channel. Palmitoyl carnitine and palmitoyl coenzyme A inhibited the Ca(2+)-ATPase at concentrations > 20 microM whereas both activated the Ca2+ release channel at concentrations < or = 20 microM in a dose-dependent manner. 4. Palmitoyl carnitine stimulated [3H]ryanodine binding to skeletal but not cardiac SR vesicles. Induction of 45Ca2+ release was observed with long-chain (C > or = 14) but not with short chain acyl carnitines (C < or = 12). 5. Long-chain acyl carnitines accumulated significantly in duckling skeletal muscle during cold acclimation. Accordingly, these results suggest that long-chain acyl metabolites may modulate SR Ca2+ cycling and its associated thermogenesis in vivo. PMID- 7990034 TI - Photoreleased inositol 1,4,5-trisphosphate-induced response in single smooth muscle cells of rat portal vein. AB - 1. The Ca2+ release in response to inositol 1,4,5-trisphosphate (InsP3) was studied in single patch-clamped smooth muscle cells of rat portal vein. InsP3 was photochemically produced from a caged InsP3 precursor included in the pipette solution. Changes in internal Ca2+ concentration ([Ca2+]i) were monitored by measuring Ca(2+)-activated K+ current. 2. Photoreleased InsP3 evoked a transient K+ current which was abolished when 10 mM EGTA or 5 mg ml-1 heparin was included in the pipette. The amplitude and time course of the K+ current responses depended on the light-flash intensity. The amplitude increased, and the latency and the time to peak decreased, with increasing flash intensity, suggesting that the amount of released Ca2+ varied as a function of the amount of InsP3 photoreleased. 3. The K+ current response to photolysis of caged InsP3 was abolished in the presence of 10 mM caffeine; conversely, caffeine was inefficient at inducing at K+ current when applied immediately after a light flash of maximal intensity. 4. The time course of the recovery of the K+ response evoked by a light flash of supramaximal intensity was similar to that obtained for the 10 mM caffeine-induced K+ current. The response recovered to 50% of control with an interval (t1/2) of about 10 s between pulses. The time course of the recovery of submaximal response to photoreleased InsP3 was considerably slower (t1/2 = 1 min), and did not correspond to that obtained for a response of similar amplitude evoked by 2 mM caffeine. 5. Responses to photoreleased InsP3 obtained after the cells were bathed for 3 min in Ca(2+)-free solution were compared with those obtained in 2 mM Ca2+ solution. Responses to light flashes of submaximal intensity were proportionally more inhibited than those evoked by supramaximal stimulations. 6. In portal vein smooth muscle cells, the InsP3-sensitive Ca2+ store seems also to be sensitive to caffeine. Our results suggest that the InsP3 induced Ca2+ release was modulated by regulatory mechanisms. PMID- 7990035 TI - Fast presynaptic GABAA receptor-mediated Cl- conductance in cultured rat hippocampal neurones. AB - 1. Hippocampal neurones cultured from the 18-day-old embryonic rat for 3 days to 3 weeks were recorded with Cl(-)-filled patch pipettes. Spontaneous synaptic currents, which reversed at the equilibrium potential for Cl- ions (ECl) and were blocked by the GABAA (gamma-aminobutyric acid) receptor antagonists bicuculline or picrotoxin, were recorded in every culture. At 25 degrees C and -80 mV they decayed with a time constant > or = 20 ms that invariably increased at positive potentials. After 2 weeks, 50-75% of all neurones were GABA immunoreactive. 2. In pairs-recordings, coincident synaptic currents in both cells were either spontaneous or evoked by stimulation of one cell. In the presence of tetrodotoxin and using pipettes containing lidocaine (lignocaine) N-ethyl bromide, coincident spontaneous Cl- transients still occurred in both neurones far more frequently than expected by chance. 3. Holding the potential of one neurone at a positive value reversed the synaptic transients in that cell and, in half of the cells, increased the frequency of coincident events in both cells. 4. In neurones where depolarization increased the frequency of coinciding events and all regenerative current apparent at the soma was abolished, short depolarizing pulses occasionally evoked all-or-none, pre- and postsynaptic currents with matching transmission failures and identical delays in transmission. 5. The results suggest that the same pulse of GABA simultaneously activates GABAA receptor coupled Cl- channels on both sides of the same synaptic cleft, producing immediate auto-transmission in the absence of collaterals or interneurones. PMID- 7990036 TI - Functional expression of A-currents in embryonic chick sympathetic neurones during development in situ and in vitro. AB - 1. The functional expression of transient voltage-activated K+ currents (IA) was examined using whole-cell recording techniques in embryonic chick sympathetic ganglion neurones that developed in situ and under various growth conditions in vitro. 2. The density of IA increased dramatically during development in sympathetic neurones isolated acutely between embryonic days 7 and 20 (E7-E20). The time course of IA inactivation became significantly faster between E7 and E13. With these protocols, neuronal differentiation and development occurred entirely in situ. 3. Sympathetic neurones isolated at E9 and maintained in vitro for 4 days did not express a normal IA compared to neurones isolated acutely at E13. Those neurones that were in physical contact with other neurones expressed normal densities of IA, but the resulting inactivation kinetics were abnormally slow. Sympathetic neurones that were cultured on the membrane fragments of lysed neurones expressed normal densities of IA even when they failed to make visible connections with other viable neurones, but the resulting inactivation kinetics were abnormally slow. Those cultured neurones that were not in physical contact with other cells or their membranes had markedly reduced densities of IA with abnormally slow inactivation kinetics. 4. Application of 5-100 ng ml-12.5 S nerve growth factor by itself did not promote normal A density of kinetics in E9 sympathetic neurones cultured for 4 days. 5. Sympathetic neurones that developed in vitro in physical contact with ventral spinal cord explants, cardiac myocytes or aortic smooth muscle cells expressed normal densities of IA, but the inactivation kinetics were abnormally slow. Cell culture media conditioned by these tissues failed to promote normal IA expression. Sympathetic neurones cultured as explants or maintained under depolarizing conditions did not express a normal IA. 6. Embryonic chick sympathetic neurones exhibit developmental changes in the density and kinetics of IA that can be regulated independently by extrinsic environmental factors including interactions with insoluble components of the plasma membranes of some cells. PMID- 7990038 TI - Mechanical retention versus bonding of amalgam and gallium alloy restorations. AB - The retention of amalgam and gallium alloy restorations in proximal box forms was measured in vitro, and three different adhesives to conventional undercuts were compared. For control, restorations were placed without undercuts or adhesives. No significant difference was found between amalgam and gallium alloys with each of the five methods of retention used. Alloys placed without retention or adhesives were significantly less retentive than all other groups. When Tytin alloy was used, no difference was found in retention among the restorations retained with Panavia or All-Bond adhesive or an occlusal dovetail and retention grooves, but Amalgambond adhesive was less retentive than all three of these methods. When gallium alloy was used, both Panavia and All-Bond adhesive were more retentive than undercuts, but the effect of Amalgambond adhesive was more retentive than undercuts, but the effect of Amalgambond adhesive was comparable to that of undercuts. The results of this study indicate that adhesives could be used in place of traditional undercuts to retain amalgam and gallium alloys, thus saving a considerable amount of tooth structure. PMID- 7990037 TI - Mechanism for reactivation of the ATP-sensitive K+ channel by MgATP complexes in guinea-pig ventricular myocytes. AB - 1. A mechanism underlying reactivation of the adenosine 5'-triphosphate-sensitive K+ (K+ATP) channels by MgATP complexes after run-down was examined in guinea-pig ventricular myocytes using the patch-clamp technique with inside-out patch configuration. 2. After run-down was induced by exposure of the intracellular side of the membrane patch to Ca2+ (1 mM), channel activity was reactivated by exposure and subsequent wash-out of MgATP (2 mM). Addition of inhibitors of various serine/threonine protein kinases to the MgATP solution did not suppress reactivation of the run-down channels. 3. Non- or poorly hydrolysable ATP analogues were unable to reactivate run-down channels. 4. The degree of channel recovery was dependent upon the duration of MgATP exposure. The apparent half activation value (K1/2) of MgATP for reactivation was decreased with increasing exposure time. 5. Various products of ATP hydrolysis were unable to reactivate run-down channels except a relatively low concentration (100 microM) of ADP exposure. 6. Other nucleotide triphosphates, in the presence of Mg2+, were unable to reactivate rundown channels. 7. Fluorescein 5-isothiocyanate (50 microM), which interacts with lysine residues of the nucleotide-binding site on various ATPases, inhibited K+ATP channel activity. After wash-out, channel activity recovered only slightly. 8. These data suggest that the hydrolysis of ATP is important for reactivation of run-down K+ATP channels but that protein phosphorylation by serine/threonine protein kinases may not be involved. Since no products of ATP hydrolysis could reproduce MgATP-induced channel reactivation and since the degree of channel recovery was dependent upon the duration of MgATP application, the hydrolysis energy appears to be utilized for channel reactivation. PMID- 7990040 TI - Thermal distortion of different materials in crown construction. AB - This study compared the thermal distortion of all-ceramic crowns with porcelain fused-to-metal crowns. The materials exhibited different responses: metal ceramic crowns stabilized after an initial loss of marginal precision, and the all ceramic crowns continued to distort with each firing cycle. PMID- 7990039 TI - Effect of porcelain surface treatments on bond strengths of composite resin bonded to porcelain. AB - A laboratory study was conducted to evaluate the bond strength of composite resin bonded to porcelain surfaces by use of a variety of treatment regimens with the All-Bond 2 adhesive system. There were significant differences in the 24-hour bond strengths between several of the surface treatment methods. The mean shear bond strength after 24 hours of water storage ranged from 10.6 +/- 2.3 MPa to 25.0 +/- 4.4 MPa. Nine of the surface treatment methods showed a significant decrease (p < 0.05) in bond strengths after 3 months of water storage and thermocycling. After 3 months, the bond strengths ranged 0.1 +/- 0.1 MPa to 17.4 +/- 2.0 MPa. Porcelain surface treatment with aluminum oxide air abrasion followed by hydrofluoric acid, a silane coupling agent, and an unfilled resin produced a bond strength after 3 months' water storage and thermocycling that was significantly greater (p < 0.05) than the other nine porcelain surface-treatment techniques. Visual examination of the debonded specimens generally showed cohesive failures in porcelain for the treatment groups with a mean bond strength above 13 MPa. PMID- 7990041 TI - Three-dimensional finite element analysis of the effects of posts on stress distribution in dentin. AB - A finite element analysis was conducted to study the influence of posts on dentinal stress in pulpless teeth. Three-dimensional models of an intact Chinese maxillary central incisor with and without post restoration were analyzed. When the tooth was subjected to masticatory and traumatic loads, stress distributions in dentin were similar whether or not the post was present. Maximal dentinal stresses were reduced by only 7% to 10% and 10% to 14.5%, respectively, with gold alloy and stainless steel posts. Thus the reinforcement effects from posts appeared limited in pulpless incisors. PMID- 7990042 TI - Improving mouth guards. AB - Mouth guards and materials were tested to provide information for a more protective yet more comfortable product. Ethylene-vinyl acetate copolymer materials varying in thickness and stiffness were tested for their mechanical, thermal, and water-absorption properties. Thickness was measured before and after fabrication of the mouth guard. During fabrication, thicknesses decreased from 25% to 50% for the custom-fabricated mouth guards and 70% to 99% for the mouth formed (boil-and-bite), off-the-shelf, over-the-counter mouth guards. The thicker the material is, the greater the resulting energy absorption is. It is therefore essential that the thickness in the occlusal portion of the mouth guard remain optimal after fabrication. A mouth guard with a stiffer insert, which softens at a higher temperature in the occlusal portion, is proposed as a more protective mouth guard. PMID- 7990043 TI - Denture tooth selection: size matching of natural anterior tooth width with artificial denture teeth. AB - This project, conducted by the Removable Prosthodontic faculty, compared the mesiodistal widths of the six maxillary anterior teeth with the widths of denture teeth from six different denture tooth manufacturers. Four hundred eighty-eight casts of dental students were measured from the distal aspect of each canine across the facial surfaces of the six anterior teeth with a flexible plastic millimeter rule. Denture teeth from six manufacturers were compared (370 molds). The results indicated that denture teeth are predominantly smaller and natural teeth are larger. PMID- 7990044 TI - Observations on long-term use of a soft-lining material for mandibular complete dentures. AB - There has been ample evidence for short-term clinical success of Molloplast-b soft-lining materials, but their use has been discouraged because of an assumed need for frequent replacement. This article presents observations on 22 patients who were provided with Molloplast-b soft-lining materials in their mandibular complete dentures for up to 9 years. Fifteen of the patients were still wearing soft-lined dentures; four had been provided with implant-supported overdentures and two had converted to hard-based dentures. In nine patients occlusal wear was a reason cited for the need to replace the complete dentures, indicating that the soft-lining material had outlasted the acrylic resin teeth. PMID- 7990046 TI - Effect of denture adhesive on the retention and stability of maxillary dentures. AB - This study used quantitative methods to measure the effects of a denture adhesive on the retention and stability of the maxillary denture. Denture movements were measured on 20 patients during standardized chewing, swallowing, and speaking activities, first with no adhesive, and then at 0, 2, 4, 6, and 8 hours after application of an over-the-counter cream adhesive. The major findings were that the denture adhesive produced a statistically significant improvement in the retention and stability of the maxillary denture during the various chewing, swallowing, and speaking activities, for up to 8 hours; there were no statistically significant differences in improvement between a poorly fitting and well-fitting denture; and patients were able to produce significantly greater levels of incisal bite force with the use of the adhesive. PMID- 7990045 TI - Sorption and solubility of 12 soft denture liners. AB - The long-term stability of a soft denture liner depends to a large extent on the sorption and solubility of the liner. Because sorption and solubility are accompanied by a volumetric change, bacterial infestation, hardening, and color change, it is a physical property of importance. The purpose of this investigation was to determine the sorption and solubility of 12 soft denture liners (Verno-Soft, Super Soft, ProTech, Soft-Pak, Flexor, Novus, Molloplast-B, Durosoft, Justi Soft, Velvesoft, VinaSoft and Prolastic). They include nine copolymers, two silicones and one polyphosphazene fluoroelastomer. The sorption and solubility test was performed as outlined in American Dental Association (ADA) specification 12 for denture base polymers. Five specimens of each material were tested and data were collected at 1 week, 1 month, 3 months, 6 months, and 1 year. Sorption data varied from 0.2 to 5.6 mg/cm2 at 1 week; 0.3 to 12.5 mg/cm2 at 1 month; 0.1 to 22.0 mg/cm2 at 3 months; 0.1 to 13.6 mg/cm2 at 6 months; and 0.1 to 35.7 mg/cm2 at 12 months. Solubility data varied from 0.0 to 0.4 mg/cm2 at 1 week; 0.1 to 0.8 mg/cm2 at 1 month; +0.1 to 1.2 mg/cm2 at 3 months; 0.0 to 1.9 mg/cm2 at 6 months; and +0.2 to 2.3 mg/cm2 at 1 year. A statistical analysis of the data by two-way ANOVA and calculated Tukey intervals showed significant differences between materials at all time intervals. The results of this study have clinical implications because the sorption and solubility may affect the long-term life expectancy of the soft denture liner. PMID- 7990047 TI - Proportioning effect on physical and chemical properties of polysulfide impression material. AB - This study investigated the effect of variation in proportioning polysulfide base and catalyst. Light, regular, and heavy-bodied pastes were mixed in linear equivalents of base-to-catalyst proportions of 30/70, 40/60, 50/50, 60/40, and 70/30. Compression set, strain in compression, and consistency tests conformed to the American Dental Association (ADA) Specification 19 guidelines. The amount of solventleachable components and differences in the cross-linked nature of the cured products were studies. Compression set and strain in compression tests met the ADA specification guidelines. Some consistency values fell outside of the ADA specification limits. The leachable content increased with increasing proportions of catalyst, but polymer cross-linking was remarkably similar for all bodied materials tested. Clinicians need not fear a significant property alteration in polysulfide impression material by the differences (within +/- 20% of the manufacturer's suggested lengths) in proportioning the component pastes with "eyeball" estimation as directed in the instructions. PMID- 7990048 TI - Evaluation of some properties of an opaque porcelain fired simultaneously with the body porcelain. AB - Recently, a porcelain-fused-to-metal opaque porcelain was introduced that does not require a separate firing before application of the body porcelain. The objective of this study was to determine the properties of this new opaque porcelain and its ability to bond to metal. The properties studied included flexural strength, linear firing shrinkage, coefficient of thermal expansion, powder particle size, and ability to bond to body porcelain and dental alloys. Sintering of this opaque porcelain was complete when fired at 1760 degrees F (960 degrees C) with a linear firing shrinkage of 13.1% +/- 0.2%. No boundary between the opaque and body porcelains could be found with a scanning electron microscope after firing at 1760 degrees F (960 degrees C). The mean flexural strengths were 99 +/- 7 and 101 +/- 8 MPa respectively, for this opaque porcelain and a conventional opaque porcelain, and were not significantly different as assessed with Student's t-test (p = 0.548). The coefficients of thermal expansion for this opaque porcelain was 13.3 +/- 0.2 x 10(-6)/degrees C. Particle size analysis showed a 63% increase in the particles below 5 microns for this opaque porcelain and bonding to two alloys was adequate as indicated by its cohesive failure. Simultaneous firing of this special opaque porcelain and body porcelain produced satisfactory sintering, strength, and bonding to metal. PMID- 7990049 TI - Diametral tensile strength and bonding to dentin of type I glass ionomer cements. AB - This study evaluated the diametral tensile strength of type I glass ionomer cements and measured their tensile and shear bond strengths to dentin with and without conditioning. Four brands of glass ionomer cement and one brand of zinc phosphate cement were tested. Disks of each cement type were prepared and the 7 day diametral compression test for tension was conducted. The shear and tensile tests, with and without 10% polyacrylic acid dentin conditioning, were performed with an Instron testing machine. Two additional groups, one for each bond test, were prepared and conditioned with 90% trichloracetic acid. No significant differences of the diametral strength were found among the various glass ionomer cements. The comparison of means suggests that, except for trichloracetic acid dentin pretreatment, the conditioning is an effective promoter of shear strength and has no significant effect (p < 0.01) on the tensile bond strength. However, trichloracetic acid was found to be a most effective dentin conditioner for both shear and tensile bond strengths (p < 0.01). PMID- 7990050 TI - A soldering index made with 4-META adhesive resin. AB - Soldering indexes are most often made of fast-setting impression plaster or autopolymerizing resin. Lack of adhesive bonding between these materials and the casting requires the use of a bulky index to support the fixed partial denture components. The advent of adhesive resins improves the quality of the index and simplifies the procedure. A procedure for making a soldering index with 4-META adhesive resin is described that involves direct bonding of the resin to the metal castings. This procedure is accurate, simple, and time-saving. It can be used inside or outside the mouth, in prosthodontic or implant dentistry. PMID- 7990051 TI - Button versus buttonless castings for removable partial denture frameworks. AB - Casting removable partial dentures (RPDs) without completely filling the sprue channels and generating casting buttons would result in saving metal and making more defect-free castings. This investigation tested whether a complete and sound RPD casting can be obtained when a minimal amount of metal is used. A factorial experimental design, three spruing methods, two metal feeding directions, and two different weights of metal were used to cast 60 Kennedy class II, modification 1 RPDs. The metal used to cast each framework was either enough to result in a full button or in no button. Visual and radiographic examinations and counting of defects were made by two independent operators who were unaware of the spruing method, feeding direction, or amount of metal used to make the framework. The completeness of the casting and the presence of porosities were evaluated for clasps, major connectors, and meshworks. The use of minimal metal to cast RPDs was equally as successful as using enough for a full button, provided that the appropriate spruing arrangement and metal feeding direction were chosen. Indirect metal feeding for maxillary RPDs was successful with the proper spruing arrangement. PMID- 7990053 TI - Management for maxillary removable partial denture patients who gag. PMID- 7990052 TI - Duplicating an existing complete denture to make a replica. AB - Sometimes it is desirable to make a few changes when making new complete dentures for a patient who has been wearing old dentures for a long time and is satisfied with them. Replica dentures can be made for these patients, and success with the new dentures can be assured. A procedure is presented for duplication of the old dentures to make replicas. PMID- 7990054 TI - A procedure for adding posterior palatal seal to an existing denture in dental office. PMID- 7990055 TI - A customized mandrel for simplifying the polishing of cranial prostheses. PMID- 7990056 TI - Neurasthenia and Chinese psychiatry in the 1990s. PMID- 7990057 TI - Repetitive strain injury. PMID- 7990058 TI - Viruses, neurosis and fatigue. AB - The evidence for viral infections as a cause of anxiety, depression and fatigue is reviewed. It is argued that in order to fully understand any proposed relationship the effects of psychosocial factors on immunity, convalescence and illness behaviour must be acknowledged. PMID- 7990059 TI - The relationship between somatosensory amplification, alexithymia, and neuroticism. AB - Both amplification of normal visceral phenomena and the personality trait of alexithymia are factors in the process of somatization, whereby somatic symptoms become metaphors for emotional distress. The relationship between these two variables was investigated in 101 psychiatric out-patients. Each subject was administered the Somatosensory Amplification Scale (SSA); the Toronto Alexithymia Scale (TAS); the NEO-FFI, which measures five personality factors; and the health locus of control (HLC). In addition, anxiety and depression were quantitatively measured. SSA and TAS significantly correlated only in the female subjects. A regression model found neuroticism to contribute the most variance in predicting SSA while TAS did not fit into the model. Amplification is a perceptual element in potentiating somatization, whereas alexithymia contributes to the cognitive aspects of the process. The role of neuroticism is discussed as a mediating factor. PMID- 7990060 TI - Alexithymia in somatoform disorder patients with chronic pain. AB - The prevalence of alexithymia in fifty-five motor vehicle accident survivors who had chronic pain complaints and met DSM-III-R criteria for somatoform pain disorder was 53%. Alexithymic and non-alexithymic patients did not differ on self reports of current pain severity or in the number of pain locations. Alexithymic patients were found to use significantly more words to describe their pain, suggesting they may have a more diffuse style in communicating their pain experience. PMID- 7990061 TI - Alexithymia and somatization: relationship to DSM-III-R diagnoses. AB - In previous studies, results from psychometric measures suggested an association between alexithymia and somatization. However, alexithymia has not been examined in relation to somatoform disorders and other standard psychiatric diagnoses. In the present study, the prevalence of DSM-III-R diagnoses was determined by SCID interviews among 45 psychiatric inpatients with functional somatic syndromes. In addition, the Toronto Alexithymia Scale (TAS) and the SCL-90-R were administered. Of the sample, 42.2% scored in the alexithymic range of the TAS. The alexithymic patients presented significantly more psychological turmoil and overall psychopathology on the SCL-90-R, as well as a significantly higher number of current DSM-III-R diagnoses. However, alexithymia was unrelated to DSM-III-R somatoform disorders and other DSM-III-R diagnoses, as well as the course of illness. These results suggest that assessing clinical features in addition to psychometric measures seems to be necessary for further validating the potential role of the alexithymia construct in somatic symptom formation. PMID- 7990062 TI - Screening women for high risk of postnatal depression. AB - A ten-item screening questionnaire was constructed from previous reports on risk factors for postnatal depression, and its ability to predict antenatally the development of postnatal depression was tested. Women attending an antenatal clinic at 36 wk gestation completed the questionnaire and, at 8 wk postpartum, were assessed for the presence of depression using the Edinburgh Postnatal Depression Scale (EPDS). Although antenatal questionnaire scores correlated significantly with postnatal EPDS scores, this was largely because the questionnaire was able to identify correctly those who would not become depressed. Neither the questionnaire as a whole, nor groups of items, was able to discriminate well between women who later did or did not become depressed. However, women who reported previous or current treatment for depression were at a threefold greater risk of becoming or remaining depressed postnatally. Possible reasons for the negative results are discussed, including the heterogeneity of depression occurring in the postnatal period. PMID- 7990063 TI - The influence of weight on adolescent self-esteem. AB - Overweight children have traditionally been thought to have lower self-esteem than other children. Prospective data from the California Child Health and Development Studies were used to test this hypothesis by examination of the relationship between body mass index, self-esteem and locus of control while controlling for demographic and baseline psychosocial traits. Principle components and confirmatory factor analysis were used to derive latent constructs for self-esteem, locus of control and other psychosocial factors. A covariance structure model was developed using the results of the confirmatory factor analysis. In this model, adolescent self-esteem, locus of control and body mass index were not related. These findings from prospective data in a non-clinical population suggest that although some subgroups of obese children may be vulnerable for decreased self-esteem, this does not appear to be a significant problem in the general population. PMID- 7990064 TI - Psychosocial factors in premenstrual dysphoria: stressors, appraisal, and coping processes. AB - Relationships between event content of daily stressors, appraisal of daily stressors, coping processes, and menstrual cycle phase were examined in women with premenstrual dysphoria (PMD) and controls. Seventy-eight women completed the Daily Rating Form, the Daily Coping Scale and the Multiple Affect Adjective Checklist-Revised on a daily basis during the premenstrual and postmenstrual phases. No premenstrual-postmenstrual differences in frequency of occurrence of stressors were reported. Academic and interpersonal stressors were the most frequently reported stressors during both cycle phases. PMD women appraised daily stressors as being more stressful, undesirable, and changeable premenstrually than postmenstrually as compared to controls. Catharsis was used more frequently premenstrually as compared to postmenstrually by PMD women. Premenstrually, women with PMD sought social support more frequently than controls. Interactive relationships between appraisal and coping style varied as a function of cycle phase for PMD women. A state-dependent model of menstrual-related mood changes is supported. PMID- 7990065 TI - Immediate-type hypersensitivity reactions and hypnosis: problems in methodology. AB - Hypnosis has been used to ameliorate skin test reactivity in studies dating back to the 1930s. This study using modern methodology and statistical analyses sets out to test the hypothesis that it was possible to decrease reactions to histamine by hypnotic suggestion. Five subjects, all asthmatic and untrained in hypnosis, were given three hypnotic sessions where they were asked to control their reactions to histamine administered by the Pepys technique to forearm skin. These sessions were to be compared with three non-hypnotic sessions. The flare sizes but not wheal sizes were found to be significantly reduced after the hypnosis sessions, compared to sessions without hypnosis. Skin temperature was correlated with the size of reactions. The day upon which the sessions took place contributed significant amounts of the remaining unexplained variance, giving rise to questions about what could cause these day to day changes. PMID- 7990066 TI - Doctors' perception of patients' cognitions and complaints in irritable bowel syndrome at an out-patient clinic. AB - Functional abdominal complaints (IBS) are widespread in the general population, especially among women. Non-organic dimensions of the complaint such as complaint related cognitions and behaviour appear to be related to the prognosis. The prognosis could possibly be improved by changing these factors during medical consultations. Therefore, doctors have to perceive patients' cognitions and behaviour. But, do they perceive them correctly? One hundred and twenty patients with functional abdominal complaints referred to an out-patient clinic for internal medicine completed a questionnaire about their complaints and their complaint-related cognitions, behaviour, and anxiety prior to the first consultation. After the first consultation, doctors completed a similar questionnaire indicating their perceptions of patients' cognitions, anxiety, behaviour, and complaints. Complaints were perceived better than cognitions, anxiety, and behaviour. Doctors underestimated patients' expectations and secondary complaints and overestimated patients' pain-related attributions, and their catastrophizing and self-efficacy cognitions. PMID- 7990067 TI - Problem-solving therapy in the treatment of unexplained physical symptoms in primary care: a preliminary study. AB - We describe a pilot study of a simple psychological treatment based on reattribution techniques and problem-solving. The treatment was administered to a consecutive series of patients (N = 11) presenting in primary care with unexplained physical symptoms. The findings suggest that the treatment is both feasible and acceptable. Finally we suggest selection criteria for those patients who may benefit from the treatment. This needs further evaluation in a randomized, controlled trial. PMID- 7990068 TI - Post-operative fatigue following coronary artery bypass surgery: relationship to emotional state and to the catecholamine response to surgery. AB - Post-operative fatigue is an important subjective problem for surgical patients, but its basis is unknown, and the possibility of a psychological component has been neglected. To investigate its putative physiological and psychological bases, 74 patients undergoing coronary artery bypass graft surgery were studied. Circulating catecholamine levels were measured at intervals perioperatively and questionnaires were used to measure fatigue, depression and anxiety up to 30 days post-operatively. We tested whether fatigue was related either to the catecholamine or to the emotional responses to surgery. The second element to the design was a controlled randomized study: patients underwent different forms of psychological preparation or a no-treatment control procedure in an attempt to test whether post-operative fatigue was amenable to psychological manipulation. Psychological preparation had no effect. Fatigue at 30 days was greatest in patients whose noradrenaline levels were greatest perioperatively. Independently of this relationship, fatigue at 30 days correlated with concurrent levels of depression and anxiety. Post-operative fatigue has both physiological and psychological correlates. PMID- 7990069 TI - The prevalence of eating disorders in thyroid disease: a pilot study. AB - The aim of this study was to determine the prevalence of eating disorders and partial syndromes in women with thyroid disease. Female patients between the ages of 18 and 45 who attended a specialist thyroid clinic, in 1990, were asked to complete two self-report questionnaires (Bulimic Investigatory Test, Edinburgh, BITE and General Health Questionnaire, GHQ). High scoring patients were invited to attend for a research interview. The case notes of non-responders were examined. Seventy-three patients were entered into the study and 50 subjects returned their questionnaires (69%). Eleven patients scored highly on the BITE, nine of these patients also scoring highly on the GHQ, as did a further 12 patients. Ten patients were interviewed; of these, three patients (4%) met DSM111R criteria for bulimia nervosa and three patients met criteria for an eating disorder not otherwise specified. These results suggest that there is an increased prevalence of eating disorders in women thyroid patients. PMID- 7990070 TI - Life events impact in patients with secondary amenorrhoea. AB - To evaluate the relationship between stressful life events and the onset of secondary amenorrhoea Paykel's semi-structured interview for Recent Life Events was administered to patients affected by secondary amenorrhea and also to healthy volunteers. The number, quality, and objective negative impact of life events were compared among different hormonal subtypes of secondary amenorrhoea and healthy normally menstruating women, as a control group. The number of life events in amenorrhoeic patients (N = 131) was significantly greater than those observed in the control group (N = 64) (45.9 vs 32.8%). Moreover, where only hypothalamic hypogonadotrophic amenorrhoea was considered, the occurrence of life events was significantly higher (59.8%) than in hyperandrogenic (26.6%) or in normogonadotrophic (20.4%) patients. The most prevalent events among hypothalamic hypogonadotrophic amenorrhoeic patients were those classified as 'undesirable', 'uncontrolled' and with 'Objective Negative Impact'. The present study supports the hypothesis of a cause-effect relationship between stressful personal life events and the onset of secondary amenorrhoea of hypogonadotrophic subtype. PMID- 7990071 TI - Behavioral treatment of scoliosis and kyphosis. AB - A behavioral treatment of scoliosis and kyphosis was tested with 27 adolescent patients (19 scoliosis, eight kyphosis patients) to determine in which cases the conspicuous and restraining brace treatment could be replaced. In 22 compliant patients, posture biofeedback (PB) was highly effective compared to five non compliant patients. Biologically more mature scoliosis patients (menarche at the beginning of treatment) seemed to profit more from PB. With kyphosis patients the PB treatment resulted in rapid straightening of the spine and removal of structural deformities of Scheuermann's disease. PB may serve as an unobtrusive yet effective treatment alternative for both juvenile scoliosis and kyphosis. PMID- 7990072 TI - Society for the Study of Fertility and the Nutrition Society, Reproduction, Growth and Development Group joint meeting. London, December 1994. Abstracts. PMID- 7990073 TI - Immunology of the testicular excurrent ducts. AB - The sperm autoantigen concentration in the epididymis equals or exceeds that in the testis. This makes the epididymis a probable site of initiation of an antisperm autoimmune response. The mechanisms regulating antisperm antibody formation in the testicular excurrent ducts and some related aspects with clinical interest are reviewed. PMID- 7990074 TI - Decidual-trophoblast interactions: decidual lymphoid cell function in normal, anembryonic, missed abortion and ectopic human pregnancy. AB - This study was designed to investigate the consequences of decidua-trophoblast interactions on the phenotype, spontaneous and induced proliferation and immunoregulatory potential of decidual leukocytes in normal pregnancies (NP), anembryonic pregnancies (AP), missed abortions (MA) and ectopic pregnancies (EP). Spontaneous proliferation of decidual non-adherent cells (NAD) from pregnancies with viable trophoblast inside the uterus is significantly higher than proliferation of peripheral blood lymphocytes (PBL) from the same groups (P < 0.001 for NP; P < 0.05 for AP). Spontaneous proliferation of decidual NAD cells from NP was higher (P < 0.001) when compared with AP and EP. The induced (PHA and Con A) responses of PBL from women with normal and pathological pregnancies were significantly higher than that of decidual NAD cells (P < 0.001). Higher proliferation of NAD decidual cells was obtained when Con A-stimulated NP were compared with MA and EP (P < 0.01). The interaction of viable trophoblast with intrauterine decidua appears to be a prerequisite for the activation of NAD suppressor cells, since NAD cells from MA produced stimulation instead of suppression, and NAD cells from EP had no suppressive effect. On the contrary, both NAD and adherent (AD) decidual leukocytes from NP and AP produced very strong suppression of PHA or alloantigen-induced PBL proliferation. The contact between trophoblast and AD decidual leukocytes is not necessary for their suppressive function, since even higher suppression is obtained with the cells from ectopic pregnancies. PMID- 7990075 TI - Experimental allergic orchitis in mice. VII. Preliminary characterization of the aspermatogenic autoantigens responsible for eliciting actively and passively induced disease. AB - Experimental allergic orchitis (EAO) can be induced actively and passively in mice by either immunization with mouse testicular homogenate (MTH) in conjunction with the appropriate adjuvants or by transferring CD4+ T cells isolated from sensitized donors into non-immunized, naive recipients. The distribution of inflammatory lesions seen in active and passive EAO are markedly different. In active EAO maximal disease is observed in the seminiferous tubules, whereas in passive EAO lesions occur primarily in the straight tubules, rete testis, and ductus efferentes. These observations suggest that different immunopathogenic mechanisms and/or aspermatogenic autoantigens may be responsible for the distinct histopathologic profiles. Two murine testis-specific aspermatogenic autoantigens (mAP1 and mAP2) were partially purified from MT acetone powder by extraction in 7 M urea under reducing conditions, gel filtration, ion-exchange chromatography, and preparative isoelectric focusing from pH 3 to 10. In gel filtration on Sephacryl S-400 in 7-M urea, mAP1 is confined to the V0 peak, while mAP2 is in the major included peak. mAP1 has an isoelectric point of 4.4-4.9, is sensitive to both pronase and DNase but not RNase, and is active at a minimal dose of 250 500 micrograms (dry wt). Dose-response bioassays for active and passive EAO revealed that mAP1 preferentially elicits active disease, whereas mAP2 is most effective at eliciting passive disease. These results support the concept that the different histopathologic profiles seen in active and passive EAO are, in part, the result of different immunopathologic responses elicited by separate aspermatogenic autoantigens. PMID- 7990076 TI - A murine model of spontaneous aspermatogenesis: linkage to H-2. AB - Experimental allergic orchitis is an organ-specific autoimmune disease characterized by inflammatory infiltrates associated with the seminiferous tubules of the testes. Orchitis is often, but not always, accompanied by aspermatogenesis in susceptible strains of mice. In this study, various strains of H-2 congenic mice were used to examine the relationship between orchitis and aspermatogenesis, and as a result, a genetic predisposition to spontaneous aspermatogenesis has been defined. A high correlation was seen between orchitis and aspermatogenesis in B10.D2/nSnJ mice, however, the two conditions were uncorrelated in C57BL/10J mice. Subsequent analysis of C57BL/10J congenic strains showed their aspermatogenesis to be spontaneous, rather than due to either testis specific antigen or adjuvants. Further studies using other H-2 congenic strains revealed that the aspermatogenesis seen in C57BL/10J mice is linked to H-2 and influenced by C57BL/10J background genes. Finally, spontaneous aspermatogenesis was shown not to be a function of differences in the level of testicular testosterone. PMID- 7990077 TI - Prevalence of mixed hypertension, isolated systolic hypertension and isolated diastolic hypertension in the elderly population in the community. AB - The prevalence of mixed hypertension (MHT), isolated systolic hypertension (ISH) and isolated diastolic hypertension (IDH) was estimated in the elderly population in the register of a large general practice in Wrexam, North Wales. Of the 3289 elderly patients, born in 1927 or before, entered in the register of surgery, 1901 attended for the first screening. The mean SBP rose with age until the age of 80-84 years in males and 75-79 years in females and then gradually declined. The mean DBP showed an earlier decline in males than in females. The prevalence of hypertension at first screening was: mixed hypertension 9.8%, ISH 19.1% (DBP < 95 mmHg*, 23.1%*) and IDH 5.7% with a total prevalence of hypertension of 52.2%. The prevalence fell at each subsequent screening so that at the third screening MHT was 3.9%, ISH 4.2% (5.4%)* and IDH 1.0%, with a total prevalence of hypertension of 10.3%. The prevalence of ISH rose with age until 70-74 years of age and with the maximum prevalence in this age group and then gradually declined. There was a drastic drop in the prevalence of both mixed hypertension and IDH after the age of 70-74 years. This study provides data for this community and also supports earlier observations that hypertension is a common problem in the elderly and that ISH is the commonest form of hypertension in the elderly. It confirms the fall in mean DBP with age but reports a decline also in mean SBP after the age of 80-84 years in males and 75-79 years in females.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7990078 TI - 24-hour ambulatory blood pressure monitoring in elderly normotensive individuals and its reproducibility after one year. AB - To study ambulatory blood pressure (ABP) and its reproducibility in healthy normotensive elderly subjects, 34 individuals were randomly selected. Their ages were 65 years (n = 10), 70 years (n = 10), 75 years (n = 8) and 80 years (n = 6). SpaceLabs 90207 system was used and one initial and a follow-up measurement after one year was performed. It was found that 24h ABP easily could be recorded in elderly subjects. A mean of 97% of the measurements were successful and only two of 34 subjects dropped out because of measurement failures. Nocturnal blood pressures were lower in all age groups and in both sexes. The standard deviations of the differences between the baseline and one year measurements were for the daytime period 8/4 mmHg and for the nighttime period 12/8 mmHg. In conclusion, ABP is easily accepted as a clinical method in normotensive elderly subjects. In all subjects there is a reduction of the nocturnal blood pressure and the reproducibility of ABP after one year is good. PMID- 7990079 TI - Angiotensin II infusions elevated blood pressure independently of platelet cytosolic calcium concentrations in humans. AB - A remarkably close correlation between platelet cytosolic calcium ([Ca2+i]) and arterial blood pressure has been identified in patients with essential hypertension. We tested the notion that a pharmacologically relevant infusion of angiotensin (Ang) II is associated with an increase in cytosolic calcium [Ca+2i]. Five normal volunteers received Ang II (5 ng/kg/min) for three hours or vehicle intravenously in random sequence respectively. The investigations were conducted at least 14 days apart. Plasma renin activity and blood pressure were measured every 20 minutes. [Ca+2i] was measured with the fluorescent indicator fura-2 before and at the end of the last hour of Ang II infusion. Mean arterial blood pressure increased by 10 mmHg during Ang II infusion (P < 0.05). Plasma renin activity decreased from 2.21 +/- 0.28 to 1.31 +/- 0.22 ng/ml/hour during the Ang II infusion (P < 0.05). On the other hand, [Ca+2i] was 131 +/- 13 nmol/l before and 129 +/- 13 nmol/l after the infusion (P = NS). The data suggest that agonists may increase blood pressure without an increase in platelet [Ca+2i]. Furthermore, Ang II may increase blood pressure independently of [Ca+2i]. PMID- 7990080 TI - Selective alpha 1-adrenergic inhibition improves decrease glucose disposal in patients with essential hypertension. AB - This study evaluated insulin secretion and insulin sensitivity before and after short-term oral administration of doxazosin in patients with essential hypertension. The hypertensive group consisted of 11 nonobese subjects (aged 41.0 +/- 2.5 years (mean +/- SEM), body mass index 24.0 +/- 0.53 kg/m2). The normotensive group consisted of 12 subjects matched to the hypertensive group for age and body mass index. The hypertensive group showed significantly higher concentrations of prestimulated and stimulated plasma insulin and plasma C peptide than normal groups. The insulin-mediated glucose disposal rate during euglycaemic clamp (M-value) was significantly lower in the hypertensive group than in normal controls (7.32 +/- 0.56 vs 8.88 +/- 0.34 mg/kg/min, P < 0.05). After one month of doxazosin treatment blood pressure was significantly reduced (P < 0.05). The short-term administration of doxazosin improved the M-value significantly to 8.60 +/- 0.62 mg/kg/min without a significant change in stimulated plasma C-peptide level. These data show that hypertension is associated with increased insulin secretion and impaired insulin sensitivity. Selective alpha 1-adrenergic inhibition with doxazosin improves the decreased glucose disposal rate associated with hypertension. PMID- 7990081 TI - Mental stress induces different reactions in nutritional and thermoregulatory human skin microcirculation: a study in borderline hypertensives and normotensives. AB - It has recently been shown that the reactivity of total (= thermoregulatory) and nutritional (= capillary) skin microcirculation differs in hypertension and normotension (NT) with a reduced stress response in hypertension. The present study investigated skin microcirculation in 40 patients with borderline hypertension (BHT) and 38 NT controls. Capillary blood flow (CBV, dynamic capillaroscopy) and subpapillary thermoregulatory flow (Laser Doppler fluxmetry, LDF) was measured at rest, after arterial occlusion and during and after a mental stress test. Resting CBV (0.48 vs. 0.50 mm/s) and LDF (3.19 vs. 3.06 AU) were equal in the two groups and no difference was found in postocclusive hyperaemia response. Reactivity to mental stress was similar in both groups with a significant increase in LDF (45% and 39%) and a significant decrease in CBV (35% and 30%). In nonsmokers the BHT group tended to increase less in LDF (50% vs. 72%) and decrease slightly more in CBV (35% vs. 28%) than the NT group. No such difference was seen in smokers. Mental stress induces opposite reactions in total and nutritional skin microcirculation both in borderline hypertensives and normotensives. There were no significant differences in reactivity between the two groups, possibly due to the alleviated responses seen in smokers in both groups. PMID- 7990082 TI - Evidence for stimulation of neutrophil degranulation by selected angiotensin converting enzyme inhibitors in vitro. AB - Polymorphonuclear neutrophils (PMN) participate in the development of myocardial injury during ischaemia/reperfusion and granules released by human neutrophils contain proteases capable of activating prorenin in human plasma and can cleave angiotensin II directly from angiotensin I and angiotensinogen. The purpose of the present study was to investigate whether angiotensin converting enzyme (ACE) inhibitors exert an in vitro effect on PMN degranulation. Isolated neutrophils were incubated with captopril, lisinopril, enalaprilat or ramiprilat and release of lysozyme and myeloperoxidase was measured from unstimulated and opsonised zymosan stimulated cells. All ACE inhibitors increased neutrophil myeloperoxidase release and lysozyme release by both unstimulated and stimulated cells. In the presence of saline unstimulated PMN released 4.48 +/- 0.68% and zymosan stimulated cells released 7.28 +/- 0.76% of myeloperoxidase content and the enzyme release increased after incubation with captopril (5.55 +/- 0.71 and 8.74 +/- 0.72%), lisinopril (5.43 +/- 0.57 and 9.02 +/- 0.7%), enalaprilat (6.05 +/- 0.67 and 9.20 +/- 0.82%) and ramiprilat (5.82 +/- 0.69 and 9.26 +/- 0.74%), respectively. In the presence of saline unstimulated PMN released 16.71 +/- 1.28% and zymosanstimulated PMN released 34.42 +/- 1.71% of lysozyme content and the release increased after incubation with captopril (21.15 +/- 1.36 and 42.75 +/- 1.95%), lisinopril (23.95 +/- 1.26 and 39.23 +/- 1.94%), enalaprilat (21.34 +/- 1.32 and 41.59 +/- 1.99%) and ramiprilat (20.88 +/- 1.35 and 37.53 +/- 1.95%) by unstimulated PMN, respectively. The ACE-inhibitory effect of these drugs may therefore be decreased by stimulation of PMN degranulation and neutrophil dependent angiotensin II forming pathway. PMID- 7990084 TI - Progress in Hypertension. Proceedings and abstracts of the 5th annual symposium of the London Hypertension Society. 1 March 1994. PMID- 7990083 TI - Lower dose diuretic therapy in the treatment of patients with mild to moderate hypertension. AB - Indapamide (Lozol), an indoline antihypertensive drug with diuretic and vasodilating activities, was evaluated in 195 patients with mild to moderate essential hypertension (sitting DBP between 95 and 110 mmHg) in a multicentre, randomised, double-blind, parallel-group design trial. A four week single-blind placebo wash-out period was followed by an eight week double-blind period. Patients were randomised to indapamide 1.25 mg/day or to placebo. The primary efficacy endpoint was the mean change in sitting DBP from baseline to week 8. Ninety patients in the placebo group (93%) and 82 patients (84%) in the indapamide group completed the eight weeks of double-blind therapy. Indapamide produced a mean (SE) decrease in sitting DBP of 7.4 (0.63) mmHg (from 100.1 to 92.8 mmHg) compared with a decrease of 3.6 (0.75) mmHg (from 99.6 to 95.8 mmHg) produced by placebo (p < 0.0001). Indapamide and placebo also produced mean decreases in standing DBP of 6.8 (0.75) and 2.8 (0.77) mmHg, respectively (p = 0.0002), in sitting SBP of 11.1 (1.18) and 3.2 (1.35) mmHg, respectively (p = 0.0001) and in standing SBP of 11.4 (1.29) and 4.0 (1.43) mmHg, respectively (P = 0.0002). Reduction in BP of > or = 10 mmHg or to a DBP of < or = 90 mmHg was more frequent (P = 0.0005) among indapamide (46.6%) compared with placebo (23.7%) treated patients. During the eight week double-blind treatment period, incidence rates for all adverse experiences and for drug-related adverse experiences were similar between the two treatment groups.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7990085 TI - Role and identification of the genes involved in human hypertension. AB - Variance of blood pressure in the normal population is composed of environmental influences and the cumulative effects of gene structure polymorphisms. Essential hypertension results from the combined influence of these components, whose respective importance can vary considerably from individual to individual. In the rare forms of hypertension due to a single gene abnormality, the environmental component is negligible and the genetic component is represented by a major transmitted gene abnormality with major effects on the phenotype. These rare forms of monogenic hypertension offer interesting models for the study of the genes involved in essential hypertension. The angiotensinogen gene represents the first example of a strongly supported implication of a gene in essential hypertension. The success of this strategy allows the possibility of identifying other genes in essential hypertension. PMID- 7990086 TI - Recent developments in endothelin research. PMID- 7990087 TI - New approaches to the diagnosis and management of renal artery stenosis. PMID- 7990088 TI - Nutritional factors in blood pressure. AB - High sodium intake, low potassium intake, high body mass index and high alcohol intake are established risk factors for high blood pressure (BP) in populations. For sodium, an overview of randomised controlled trials gave the estimate that reduction in sodium of around 70 mmol per day lowered BP on average by 2.9 mmHg systolic and 1.6 mmHg diastolic. An overview of within-population epidemiological studies (excluding INTERSALT), with correction for regression dilution, gave a pooled (simple) regression estimate that 100 mmol lower sodium was associated with BP lower by 4.5 mmHg systolic and 2.5 mmHg diastolic. In INTERSALT, across centres, average sodium excretion was significantly related to slope of BP with age, such that 100 mmol lower sodium was associated with 10 mmHg lower rise in SBP over 30 years; among individuals, previous estimates of the size of relationships of sodium and potassium to BP in INTERSALT were too low because of insufficient correction for the 'regression dilution' problem. For sodium, revised corrected regression estimates, with adjustment for age and sex, were 4.3 mmHg/100 mmol for SBP and 1.8 mmHg/100 mmol for DBP. After adjustment for other confounders, the corrected SBP-sodium regression estimate was 3.1 mmHg/100 mmol; it was 6.0 mmHg/100 mmol if body mass index was excluded from the regression model. The revised multiply adjusted regression estimate for SBP and potassium was -0.67 mmHg/10 mmol. Body mass index was positively related to BP in INTERSALT, consistent with other studies; on average, regression coefficients indicated 3.0 mmHg lower SBP and 2.2 mmHg lower DBP, for body weight lower by 10 kg.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7990089 TI - Hypertension in the very elderly. PMID- 7990090 TI - Production of atrial natriuretic peptide and cell proliferation in ventricular myocytes given angiotensin II in culture. PMID- 7990091 TI - Investigation of the renin gene as a putative locus for essential hypertension (EH) in Vincentian African Caribbeans. PMID- 7990092 TI - ACE insertion/deletion (I/D) polymorphism in Vincentian African Caribbeans with essential hypertension. PMID- 7990093 TI - Investigation of lipoprotein lipase (LPL) as a candidate gene for dyslipidaemic hypertension. PMID- 7990094 TI - Isolation of single vascular smooth muscle cells from human omental resistance arteries. AB - Small arteries less than 500 microns make a significant contribution to peripheral vascular resistance. Single vascular smooth muscle cells were isolated from human omental resistance arteries by enzymatic dispersion. The method yielded relaxed vascular smooth muscle cells approximately 120 microns long and 7 microns wide. The cells were studied using whole cell voltage clamp techniques and a number of passive and active membrane properties were described. PMID- 7990095 TI - Are the changes in urinary kallikrein excretion on altering sodium intake an index of salt sensitivity? PMID- 7990096 TI - Resistance artery morphology in essential hypertension and in normal subjects: some methodological considerations. AB - Although it is generally assumed that small arteries are truly isometric when studied in a myograph, these arteries significantly shorten during the normalisation procedure. We assessed the effects of this shortening on calculation of morphological variables in small arteries using vessel length before and after normalisation. Subcutaneous resistance arteries were dissected from gluteal biopsies obtained from normotensive subjects (n = 7, supine pressure 116/69 +/- 5/3(SE) mmHg, internal artery diameter 276 +/- 16 microM) and patients with essential hypertension on no treatment (n = 13, supine pressure 160/102 +/- 4/2 mmHg, internal diameter 256 +/- 9 microM) mounted on a small vessel myograph. Using the actual shortened 'normalised' length compared with measurement using the original artery length, media thickness was significantly greater both in normal subjects (24.0 +/- 2.7 microM vs. 22.7 +/- 2.7 microM, 2 P < 0.05, paired t-test) and in hypertensives (27.6 +/- 1.5 microM vs. 26.5 +/- 1.4 microM, 2 P < 0.001). Calculated from the actual shortened 'normalised' length vs. original artery length, media:lumen ratio was also increased in the normal subjects (8.6 +/- 0.6 vs. 8.2 +/- 0.6 2 P < 0.05) and in the hypertensives (11.2 +/- 0.7 vs. 10.7 +/- 0.7, 2 P < 0.001). For the media thickness in normal subjects this was an increase of 6% (95% CI: 1-12%) and in hypertensives of 4% (95% CI: 2-6%). Standard methods for study of small arteries underestimate media thickness and media:lumen ratio in normal subjects and in hypertensives.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7990097 TI - Acute natriuretic effect of nifedipine on different sodium intakes in essential hypertension: evidence for distal tubular effect? PMID- 7990098 TI - The Hypertension in the Very Elderly Trial (HYVET). PMID- 7990099 TI - Polymorphisms in the gene encoding angiotensin 1-converting enzyme and relationship to its post-translational product in cerebral infarction. AB - There is increasing evidence to suggest that the gene encoding angiotensin 1 converting enzyme (ACE) plays a significant part in cardiac disease risk. It is not clear if this risk is due to atherosclerotic factors in general or whether its influence is local to cardiac tissue. Previous studies have suggested that there is a genetic control of plasma ACE levels in normal subjects. We sought to see if such a relationship also existed amongst computer tomography (CT) proven cerebral infarction. Twenty-eight patients with stroke and 19 control subjects were grouped according to their ACE genotype and their plasma ACE levels were assessed. Although there is a trend for plasma levels to be associated with the variant ACE alleles there was a wide overlap. However, when compared with their respective alleles in control subjects there was no difference. We conclude that any future evaluation of stroke risk from the ACE gene will need to determine both plasma ACE level and genotype. PMID- 7990100 TI - Angiotensin-1 converting enzyme (ACE) polymorphism in patients presenting with myocardial infarction or unstable angina. AB - A deletion/insertion polymorphism in the ACE gene has been reported previously as a potent factor for myocardial infarction. We have tested the frequency of the deletion (D) allele of the ACE gene in 308 consecutive patients admitted to coronary care with chest pain. The gene frequencies were compared with those of 348 controls recruited from the London area. Of 108 Caucasian patients with myocardial infarction, the DD genotype was found more frequently than the combined DI and II genotypes (Chi-square, chi 2 = 5.07, 2P = 0.024). The overall D gene frequency was higher in myocardial infarction patients (125 of 216, 58%) than in controls (347 of 696, 49.9%) (chi 2 = 3.79, 2P = 0.052). In contrast, the DD genotype and D allele frequencies in patients with unstable angina were similar to those found in our normal population. A nonsignificant difference in allele frequency between myocardial infarction and unstable angina patients was observed but the small numbers of subjects studied precludes a more formal comparison. Since unstable angina and myocardial infarction represent a spectrum of coronary thrombosis, it is possible that the DD genotype favours the development of myocardial infarction, perhaps through the presence of higher serum ACE concentrations. PMID- 7990101 TI - Angiotensinogen Met235-->Thr polymorphism in a London normotensive and hypertensive black and white population. AB - We describe angiotensinogen gene (AGT) polymorphic frequencies in different ethnic groups in London, both normotensive and hypertensive. The methodology is a recently described direct PCR technique. Results show that there is a marked difference in T-235 frequency between ethnic groups. However, there was no apparent association of T-235 with hypertension. PMID- 7990102 TI - Lack of acute effects of a standardised fat meal or exercise on erythrocyte sodium-lithium countertransport activity. PMID- 7990103 TI - Molecular approach to assessing the genetic risk of cerebral infarction: deletion polymorphism in the gene encoding angiotensin 1-converting enzyme. AB - Numerous factors have been reported to influence the pathogenesis of stroke. The risks arising from variations in genes between individuals have not been explored. The angiotensin 1-converting enzyme gene is a candidate gene for atherosclerotic related disease. In this work we studied the frequency of the deletion allele D and the polymorphism DD within the gene encoding angiotensin 1 converting enzyme in stroke patients compared with controls to determine if this deletion polymorphism was a potential independent risk factor for stroke. We report a study of 100 patients with cerebral infarction along with 73 normal age and sex matched controls. Personal medical histories associated with high risk factors for stroke were documented. Cholesterol and triglyceride levels for each individual were also measured. Using polymerase chain reaction techniques patients were divided into the three angiotensin 1-converting enzyme genotypes (Deletion D and Insertion I) II, ID and DD. The D/I frequency in patients with stroke (0.57/0.43) was compared with controls (0.48/0.52). This was not statistically different (P > 0.05, chi-squared test). Although strokes did occur at a younger age in those with the DD genotype compared with those with the insertion allele, the results did not approach acceptable levels of significance (II/ID) (P > 0.05, Mann-Whitney U-test). There were no differences between the three genotypes and other well accepted risk factors for stroke.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7990104 TI - The glycine site on the NMDA receptor: structure-activity relationships and therapeutic potential. PMID- 7990105 TI - A highly potent, orally active imidazo[4,5-b]pyridine biphenylacylsulfonamide (MK 996; L-159,282): a new AT1-selective angiotensin II receptor antagonist. PMID- 7990107 TI - Multisubstrate inhibition of 4-hydroxybenzoate 3-monooxygenase. PMID- 7990106 TI - GC sequence specific recognition by an N-formamido, C-terminus-modified and imidazole-containing analogue of netropsin. PMID- 7990109 TI - Bioisosteres of arecoline: 1,2,3,6-tetrahydro-5-pyridyl-substituted and 3 piperidyl-substituted derivatives of tetrazoles and 1,2,3-triazoles. Synthesis and muscarinic activity. AB - A series of arecoline bioisosteres, where the ester group is replaced by a 1,2,3 triazole-4-yl or a tetrazole-5-yl group, was synthesized and evaluated in vitro for affinity and efficacy at muscarinic receptors and in vivo for cholinergic side effects. The corresponding piperidine derivatives were also studied. In the 1,2,3,6-tetrahydropyridyl-1,2,3-triazole series, only derivatives with 2 substituents in the 1,2,3-triazole ring exert muscarinic agonist activity. The same trend is seen in the corresponding tetrazole series, where only 2 substituted derivatives display muscarinic agonist activity. The methyl derivatives in both series are full agonists, whereas the derivatives with longer side chains are partial agonists. Introduction of methyl substituents in the 1,2,3,6-tetrahydropyridine ring generally lowers affinity considerably except for the 3-substituted derivatives, where some activity is retained. In both the 1,2,3 triazole and tetrazole series, derivatives without substituents at the basic nitrogen in the 1,2,3,6-tetrahydropyridine ring are unselective full agonists, whereas the methyl-substituted derivatives generally are more M1 selective compared to M2. Larger substituents than methyl abolish activity. The 4-(3 piperidyl)-1,2,3-triazole and 5-(3-piperidyl)-2H-tetrazole derivatives are generally less active than the corresponding 1,2,3,6-tetrahydropyridine derivatives, and only the 2-allyl- and 2-propargyl-1,2,3-triazole derivatives display activities comparable to the most active compounds in the 1,2,3,6 tetrahydropyridine series. The propargyl derivative is an unselective full agonist, and resolution did not reveal any stereoselectivity The allyl derivative is a partial agonist with some selectivity for the M1 receptor, and testing of the enantiomers showed that the (+)-enantiomer is an unselective partial agonist, whereas the (-)-enantiomer is a partial agonist with preference for the M1 receptor. Generally, the structure-activity relationships of the 1,2,3-triazole and tetrazole series are very similar, and two compounds, 2-ethyl-4-(1-methyl 1,2,3,6-tetrahydro-5-pyridyl)-1,2,3-triazole and 2-ethyl-5-(1-methyl-1,2,3,6 tetrahydro-5-pyridyl)-2H-tetrazole, are M1 agonists/M2 antagonists. Muscarinic compounds with this profile are of particular interest as drugs for the treatment of Alzheimer's disease. PMID- 7990108 TI - Novel antiproliferative agents derived from lavendustin A. AB - The active partial structure of the potent tyrosine kinase inhibitor lavendustin A was derivatized in the search for novel agents against cellular proliferation. The antiproliferative potential of the new derivatives was determined using the human keratinocyte cell line HaCaT as the primary test system. Whereas the lavendustin A partial structure is ineffective in inhibiting cell proliferation, esterification of its carboxylic acid function leads to measurable antiproliferative activity. Additional O-methylation of the 2,5-dihydroxyphenyl moiety yields activity in the micromolar range. Further substantial increases in activity are achieved by replacing the nitrogen with oxygen and carbon within the 2,5-dimethoxyphenyl series (but not within the 2,5-dihydroxyphenyl analogs) leading to 5-[2-(2,5-dimethoxyphenyl) ethyl]-2-hydroxybenzoic acid methyl ester (13) as the most potent analog identified to date. These increases in antiproliferative activity are paralleled, however, by the disappearance of activity against the epidermal growth factor receptor-associated tyrosine kinase, suggesting another mechanism of action. PMID- 7990110 TI - A comparative molecular field analysis model for 6-arylpyrrolo[2,1-d] [1,5]benzothiazepines binding selectively to the mitochondrial benzodiazepine receptor. AB - A series of 42 6-arylpyrrolo[2,1-d][1,5]benzothiazepines, which we have recently described as selective ligands of the mitochondrial benzodiazepine receptor (MBR) (Fiorini I.; et al. J. Med. Chem. 1994, 37, 1427-1438), have been investigated using the comparative molecular field analysis (CoMFA) approach. The resulting 3D QSAR model rationalizes the steric and electronic factors which modulate affinity to the MBR with a cross-validation standard error of 0.648 pIC50 unit. A set of seven novel pyrrolobenzothiazepine congeners has successively been synthesized and tested. The CoMFA model forecasts the binding affinity values of these new compounds with a prediction standard error of 0.536. PMID- 7990111 TI - Conformational analysis, pharmacophore identification, and comparative molecular field analysis of ligands for the neuromodulatory sigma 3 receptor. AB - Molecular modeling studies were carried out on a series of 1-phenyl-3-amino 1,2,3,4-tetrahydronaphthalenes (phenylaminotetralins, PATs), several PAT structural analogs, and various non-PAT ligands that demonstrate a range of affinities for a novel sigma 3 receptor linked to stimulation of tyrosine hydroxylase and dopamine synthesis in rodent brain. In an effort to develop a ligand-binding model for the sigma 3 receptor, a pharmacophore mapping program (DISCO) was used to identify structural features that are common to ligands that exhibit moderate to high binding affinity for sigma 3 sites. DISCO then was utilized to propose a common pharmacophoric region that included one low-energy conformation of each compound in the training set. The resulting alignment was utilized in a comparative molecular field analysis (CoMFA) study in an attempt to correlate the steric and electrostatic fields of the molecules with the respective binding affinities at the sigma 3 receptor. A suitably predictive model was obtained from the CoMFA analysis which will be employed in the development of additional PAT analogs that could potentially display high affinity and selectivity for the sigma 3 receptor. The excluded volumes which resulted from comparing molecular volumes of active and inactive compounds were visualized to examine the limits of steric tolerance imposed by the sigma 3 receptor. PMID- 7990112 TI - Substrate specificity in short-chain phospholipid analogs at the active site of human synovial phospholipase A2. AB - The substrate specificity at the active site of recombinant human synovial fluid phospholipase A2 (hs-PLA2) was investigated by the preparation of a series of short-chain phospholipid analogs and measurement of their enzymatic hydrolysis at concentrations well below the critical micelle concentration. Substrates used in the study included 1,2-dihexanoylglycerophospholipids, 1,2 bis(alkanoylthio)glycerophospholipids, and 1-O-alkyl-2 (alkanoylthio)phospholipids. Turnover was observed for only a few of the 1,2 dihexanoylglycerophospholipids, and the rate of hydrolysis was very low, near the limit of detection of the assay. In contrast, selected 2-(alkanoylthio) glycerophospholipids were hydrolyzed by hs-PLA2 at much higher rates at concentrations well below their critical micelle concentration (cmc). Thus, the 1,2-bis(hexanoylthio)glycerophosphatidylmethanol exhibits a k(cat)/K(M) = 1800 L mol-1 s-1. Over the calculated log P (cLogP) range of 3-9, cLogP and log(k(cat)/K(M) were linearly related for compounds with straight-chain sn-1 and sn-2 substituents. At comparable cLogP's, the sn-1 ethers and thioesters were hydrolyzed at comparable rates. A negative charge in the phosphate head group was required for enzyme activity. Unsaturation, aromaticity, and branching in the sn 2 substituent reduce turnover dramatically. The same structural modifications in the sn-1 substituent have less effect on turnover. Certain of these substrates, e.g., 1,2-bis(hexanoylthio)glycerophosphatidylmethanol, may be useful in assaying for active site inhibitors of PLA2. The structure--activity relationships established here for substrates should serve as a reference for the structure- activity relationships of substrate-based inhibitors. PMID- 7990113 TI - Molecular similarity indices in a comparative analysis (CoMSIA) of drug molecules to correlate and predict their biological activity. AB - An alternative approach is reported to compute property fields based on similarity indices of drug molecules that have been brought into a common alignment. The fields of different physicochemical properties use a Gaussian-type distance dependence, and no singularities occur at the atomic positions. Accordingly, no arbitrary definitions of cutoff limits and deficiencies due to different slopes of the fields are encountered. The fields are evaluated by a PLS analysis similar to the CoMFA formalism. Two data sets of steroids binding to the corticosteroid-binding-globulin and thermolysin inhibitors were analyzed in terms of the conventional CoMFA method (Lennard-Jones and Coulomb potential fields) and the new comparative molecular similarity indices analysis (CoMSIA). Models of comparative statistical significance were obtained. Field contribution maps were produced for the different models. Due to cutoff settings in the CoMFA fields and the steepness of the potentials close to the molecular surface, the CoMFA maps are often rather fragmentary and not contiguously connected. This makes their interpretation difficult. The maps obtained by the new CoMSIA approach are superior and easier to interpret. Whereas the CoMFA maps denote regions apart from the molecules where interactions with a putative environment are to be expected, the CoMSIA maps highlight those regions within the area occupied by the ligand skeletons that require a particular physicochemical property important for activity. This is a more significant guide to trace the features that really matter especially with respect to the design of novel compounds. PMID- 7990114 TI - Syntheses of racemic and nearly optically pure ether lipids and evaluation of in vitro antineoplastic activities. AB - In addition to rac-2-O-methyl-1-O-octadecylglycero-3-phosphocholine (rac-ET-18 OCH3, rac-Edelfosine, 1), three racemic ether lipid analogs, 4, 5, and 6, were synthesized where N,N-dimethylamino, N-methylpyrrolidino, and N-methylmorpholino groups, respectively, have been substituted for the trimethylammonio group. The two enantiomers, (R)-ET-18-OCH3 (2) and (S)-ET-18-OCH3 (3), and all four possible chiral methylcholine analogs, 7, 8, 9, and 10, of (R)-ET-18-OCH3 (2) were also synthesized. Three human leukemic cell lines (CEM, HUT 78, and Namalwa) were used to assess the in vitro antineoplastic properties of these 10 ether lipid analogs. At ether lipid concentrations of 5-50 micrograms/mL, dose- and time-dependent cytotoxicities were demonstrated up to 24 h. CEM and HUT 78, both T cell derived, were more sensitive to the ether lipids than Namalwa, which is B cell derived. rac-ET-18-OCH3 (1) with its R and S enantiomeric forms, 2 and 3, respectively, exhibited modest stereoselectivity in HUT 78 and Namalwa with 1 and 2 slightly more cytotoxic than 3. Ether lipid (EL) analogs 4, 5, and 6 demonstrated significantly greater cytotoxicity in normal peripheral lymphocytes, 4 and 6 exhibited a modest increase in cytotoxicity in HUT 78 and Namalwa (P < 0.05), and 5 demonstrated greater cytotoxicity (P < 0.05) in Namalwa than the parent EL 1. The calculated 24 h ID50 values suggest that the beta-methyl analogs, 9 and 10, were more cytotoxic than the alpha-methyl analogs, 7 and 8, in all the tested cancer cell lines. PMID- 7990115 TI - The synthesis and in vitro evaluation of a 99mtechnetium-nitroimidazole complex based on a bis(amine-phenol) ligand: comparison to BMS-181321. AB - We have developed a 99mTechnetium complex for imaging of hypoxic tissue (BMS 181321). Recently, another nitroimidazole derivative, based upon a bis(amine phenol) ligand, was described in the patent literature. To compare this compound to BMS-181321, we have synthesized the ligand, prepared its 99mTc complex, and evaluated its performance in two in vitro assays of bioefficacy: membrane permeability and uptake in normoxic and anoxic cardiocytes. In attempting to reproduce the synthesis of the ligand described in the patent application, we found that one intermediate could not be made by the method described, and alternative routes were investigated. Complexation of the bis(amine-phenol) nitroimidazole with 99mTc gave an apparent single complex; this appeared as a broad peak on HPLC analysis. Purification by a solid-phase method gave a complex with 95% radiochemical purity. This complex was not permeable to cultured bovine brain endothelial cells nor did it show preferential uptake in anoxic myocytes. PMID- 7990116 TI - Quantitative structure-activity relationships/comparative molecular field analysis (QSAR/CoMFA) for receptor-binding properties of halogenated estradiol derivatives. AB - The 3-D quantitative structure-activity relationships/comparative molecular field analysis (QSAR/CoMFA) paradigm, which considers the primary importance of the molecular fields in biological recognition, is now widely used to analyze and predict receptor-binding properties of various ligands. CoMFA was applied to build 3-D QSAR models of substituted estradiol-receptor interactions, employing 3 D molecular databases of more than 40 molecules. Ligands included the 17 alpha ethynyl- and isomeric 17 alpha (20E/Z)-(iodovinyl)estradiols and their 7 alpha-, 11 beta-, and 12 beta-methyl (-methoxy) and -ethyl (-ethoxy) derivatives as well as selected 2- and 4-halogenated analogs. The influence of different CoMFA descriptors was studied in order to achieve the highest possible cross-validated r2, as derived from partial least-squares calculations. Special emphasis was put on the analysis of the nature of H-bonding (donor/acceptor) interactions. The model with the best predictive performance (r2 = 0.895) was used to visualize steric and electrostatic features of the QSAR (standard deviation*coefficient contour maps) and to predict receptor-binding affinities (RBA) of substituted estradiols other than those included in the original database. Twenty-seven test molecules were selected, including five which had previously been reported by other investigators. For the latter, a very good correlation with literature RBA values was obtained, which together with the high cross-validated r2 provides evidence for the high predictive capacity of the model. Among the unknown structures, the model suggests several new substitutions to derive at reasonable affinity ligands for the estrogen receptor. PMID- 7990117 TI - An evaluation of the antirhinoviral activity of acetylfuran replacements for 3 methylisoxazoles. Are 2-acetylfurans bioisosteres for 3-methylisoxazoles? AB - As a probe of the 3-methylisoxazole portion of our broad-spectrum antipicornaviral series, a panel of 2-acetylfuran analogues was prepared as replacements for the 3-methylisoxazole ring. Comparison of the two series showed remarkable similarity in potency, spectrum of activity, logP, and electrostatic parameters. X-ray studies of 21b bound to human rhinovirus-14 showed that the 2 acetyl group adopted a syn conformation and the carbonyl oxygen acts as a hydrogen bond acceptor with ASN219 in much the same way as the nitrogen of the isoxazole. The importance of the syn conformation and the hydrogen-bonding capability was confirmed by the reduced antiviral activity of the 2-methylfuran and 2-formylfuran analogues. From the results of this study, it is apparent that the syn-2-acetylfuran ring is acting as a bioisostere for the 3-methylisoxazole. PMID- 7990118 TI - 7-azetidinylquinolones as antibacterial agents. 2. Synthesis and biological activity of 7-(2,3-disubstituted-1-azetidinyl)-4-oxoquinoline- and -1,8 naphthyridine-3-carboxylic acids. Properties and structure-activity relationships of quinolones with an azetidine moiety. AB - A series of 7-(2,3-disubstituted-1-azetidinyl)-1,4-dihydro-6-fluoro-4- oxoquinoline- and -1,8-naphthyridine-3-carboxylic acids, with varied substituents at the 1-, 5-, and 8-positions, was prepared to study the effects on potency and physicochemical properties of the substituent at position 2 of the azetidine moiety. The activity of the title compounds was determined in vitro against Gram positive and Gram-negative bacteria, and the in vivo efficacy of selected derivatives was determined using a mouse infection model. The X-ray crystal structures of 6b, 6c, and 6d were found to be in reasonable agreement with the corresponding AM1 calculated geometries. Correlations between antibacterial potency of all the synthesized 7-azetidinylquinolones and naphthyridines and their calculated electronic properties and experimental capacity factors were established. Antibacterial efficacy and pharmacokinetic and physicochemical properties of selected derivatives were compared to the relevant 7-(3-amino-1 azetidinyl) and 7-(3-amino-3-methyl-1-azetidinyl) analogues (for Part 1, see: J. Med. Chem. 1993, 36, 801-810). A combination of a cyclopropyl or a substituted phenyl group at N-1 and a trans-3-amino-2-methyl-1-azetidinyl group at C-7 conferred the best overall antibacterial, pharmacokinetic, and physicochemical properties to the azetidinylquinolones studied. PMID- 7990119 TI - Structure-activity relationships and pH dependence of binding of 8-alkyl-N5 deazapterins to dihydrofolate reductase. AB - Thermodynamic dissociation constants (Kd) have been determined for two series of 8-alkyl-N5-deazapterins in binary complexes with human and chicken dihydrofolate reductases (DHFRs) and ternary complexes with the enzyme.NADPH complex. For an initial series of 12 compounds with variable 8-alkyl substitutents and pyrazine ring-methyl substitution patterns, Kd values at pH 6.6 were found to range from > 100 to 0.5 microM, with consistent trends depending on the enzyme source, the size of the 8-substituent, and the presence and position of the pyrazine ring methyl substituent. For most compounds in this first series, Kd values were significantly lower for the ternary complex than for the binary complex with ratios of Kd(binary)/Kd(ternary) ranging from 0.6 to 62, suggesting a degree of cooperativity in binding to the enzyme between ligand and cofactor. This effect was more pronounced for the human enzyme. The structure-activity relationships developed in the first series suggested a number of strategies for developing ligands with greater affinity for DHFR. These were tested with a second series of four compounds. The Kd of 80 nM at pH 6.6 of one of these compounds [5-methyl- 8 isobutyl-N5-deazapterin (15)] in ternary complex with human DHFR is more than 200 times lower than that for the lead compound (8-methyl-N5-deazapterin (1); Kd 21 microM). Studies of binding stoichiometry indicated two binding sites in binary complexes with DHFR for 8-alkyl-N5-deazapterins with smaller 8-substituents. The second site was not found in ternary complexes or for ligands with larger 8 substituents, suggesting that the second ligand molecule in binary complexes is probably binding in the cofactor site and that the larger 8-substituents also bind in this area. A detailed study of the inhibition kinetics for one compound, 6,8-dimethyl-N5-deazapterin (5), showed it to be a competitive inhibitor of the chicken DHFR-catalyzed reduction of 6,8-dimethylpterin suggesting that the 8 alkyl-N5-deazapterins bind in the substrate site of DHFR. The pH dependence of the binding of several ligands in binary and ternary complexes with DHFR was examined by determining their Kd values at a range of pH's. This suggested that binding was predominantly between protonated ligand and deprotonated enzyme, but with variable contributions to binding observed between deprotonated enzyme and neutral ligand, and protonated enzyme and protonated ligand, depending on compound and complex type. PMID- 7990120 TI - Latent alkyl isocyanates as inhibitors of aldehyde dehydrogenase in vivo. AB - On the basis of our previous observation that N1-alkyl substituted chlorpropamide derivatives when administered to rats nonenzymatically eliminated n-propyl isocyanate, a known inhibitor of aldehyde dehydrogenase (AlDH), we have synthesized other latentiated n-propyl isocyanates as in vivo inhibitors of AlDH. N1-Allylchlorpropamide 3 was, as expected, a potent inhibitor of hepatic AlDH in rats, as indicated by the 4-fold increase in the levels of ethanol-derived blood acetaldehyde relative to that elicited by chlorpropamide itself. Closely following in activity in decreasing order were N3-(n-propylcarbamoyl)uracil (7),N (n-propylcarbamoyl)saccharin (6), and the S-(n-propylcarbamoyl) derivative (9) of benzyl mercaptan. However, two hydantoin derivatives, 5 and 8, were totally inactive in inhibiting AlDH in vivo. A prodrug of N1-ethylchlorpropamide, viz., its N3-trifluoroacetyl derivative (4b), was a good in vivo inhibitor of AlDH, mimicking the activity of the parent N1-ethylchlorpropamide. These results suggest that latent alkyl isocyanates are inhibitors of AlDH, giving further support to the hypothesis that the inhibition of AlDH in vivo by the hypoglycemic agent chlorpropamide may be due to the release of n-propyl isocyanate following metabolic bioactivation. PMID- 7990121 TI - Androgen receptor affinity of 5'-acyl furanosteroids. AB - Syntheses of 5'-acyl furanosteroids are described from the corresponding unsubstituted [3,2-b]furanosteroids using acid anhydrides and acid chlorides in the presence or absence of Lewis acids. New methods have been developed to prepare 5'-acetyl derivatives: reduction of a 5'-trichloroacetyl intermediate either by sodium formaldehyde sulfoxylate or with 10% Pd/C. Most of these 5'-acyl derivatives bind to the rat ventral prostate androgen receptor. However the antiandrogenic activity was diminished when compared with 4,5'-methylsulfonyl furanosteroid. Biological studies revealed that 5'-acyl furanosteroids were either androgens or modest antiandrogens. The electrostatic potential maps of the substructures of 3, 4, and 5'-acetyl syn- and anti-furanosteroids showed striking differences which may explain, to some extent, the lack of significant antiandrogenic activity of 5'-acyl furanosteroids. PMID- 7990122 TI - Effect of molecular manipulation on the estrogenic activity of a brain-targeting estradiol chemical delivery system. AB - The structural parameters important for biological efficacy of an estradiol chemical delivery system (CDS), a brain-targeting approach based on redox trapping, were examined by molecular manipulation of a prototype derivative, estradiol 17-(1-methyl-1, 4-dihydronicotinate) (E2-CDS). Seven E2-CDS analogs in which the N-methyl substituent was altered were prepared including N-substituted short and medium straight chain alkyl, short branched chain alkyl, and aralkyl derivatives. Chemical and in vitro testing indicated that the most stable derivative was the N-benzyl E2-CDS. The analogs were tested in an intact male rat model to assess various central estrogenic manifestations including the rate of body weight gain, serum E2 and testosterone concentrations, and seminal vesicle, prostate and pituitary weight changes. Results indicated that all prepared CDS derivatives exerted some degree of central estrogenization with the most potent compounds being the parent E2-CDS and its ethyl homologue. Importantly, while the ethyl E2-CDS was equipotent to E2-CDS in various biological assays, it did not significantly elevate serum E2 compared to vehicle control at day 14. PMID- 7990123 TI - Iodinated 2-aminotetralins and 3-amino-1-benzopyrans: ligands for dopamine D2 and D3 receptors. AB - In developing selective ligands for dopamine D2 and D3 receptors, several iodinated 2-aminotetralins and 3-amino-1-benzopyrans, trans-7-hydroxy-2-[N-(3' iodo-2'- propenyl)amino]tetralin (1), trans-monohydroxy-2-[N-propyl-N-(3'-iodo-2' propenyl)amino]tetralin (7-, 5-, and 6-OH-PIPAT) (2, 3, and 4), and trans monohydroxy-3,4-dihydro-3-[N-propyl-N-(3'-iodo-2'- propenyl)-amino]-2H-1 benzopyran (6- and 8-OH-benzopyrans) (5 and 6), were prepared. These compounds were evaluated for their binding profiles in several membrane preparations: Spodoptera frugiperda (Sf9) cells expressing dopamine D2 (non-GTP coupled, low affinity states) and D3 receptors, HEK293 cells expressing dopamine D2 receptors in high-affinity states (D2H), rat hippocampal homogenates for 5-HT1A receptors, and cerebellar homogenates for sigma receptors. The mono-N-alkylated 2 aminotetralin, 1, displayed high sigma binding (Ki = 1.68 nM) with a moderate D3 binding (Ki = 30.2 nM). Derivatives with one N-propyl and one N-(3'-iodo-2' propeny) group generally displayed high to moderate affinity to D3 receptors (Ki = 2.90, 1.85, 0.99, 2.20, 31.4, and 6.69 nM for 7-OH-DPAT [7-hydroxy-2-(N,N-di-n propylamino)tetralin], 2, 3, 4, 5, and 6, respectively). It is interesting to note that all of the active D3 ligands also displayed comparable binding to the high affinity states of D2 receptors in HEK293 cells (Ki = 6.6, 3.6, 9.7, and 10.8 nM for 2, 3, 4, and 6, respectively). Among all of the tetralin derivatives tested, 5-OH-PIPAT, 3, showed the highest binding affinity to D3 receptors (Ki = 0.99 nM) and better selectivity (KiD2H/KiD3, KiD2/KiD3, Ki5-HT1A/KiD3 and Ki sigma/KiD3 = 3.64, 327, 48.4, and 1250 nM, respectively), making it the best ligand for studying dopamine D2H and D3 receptors. PMID- 7990125 TI - 4-Deacetyltaxol and 10-acetyl-4-deacetyltaxotere: synthesis and biological evaluation. AB - 4-Deacetyltaxol and 10-acetyl-4-deacetyltaxotere were synthesized for the first time from 7-(triethylsilyl)-4-deacetylbaccatin III. These analogs were found to be inactive in the microtubule assembly assay. PMID- 7990124 TI - Studies of the active conformation of a novel series of benzamide dopamine D2 agonists. AB - Analogs of dopamine D2 agonist 11 were prepared in which a rigid trans decalin ring system was used to mimic various conformations of 11. The four rigid analogs where compared for their ability to bind to the DA D2 receptor and to inhibit forskolin-stimulated cAMP formation, a measure of DA agonist activity. Of the four rigid analogs of compound 11, only compound 12b had significant activity in both assays. Molecular modeling studies of 12a-d showed each had a single conformation with regard to the distance between the benzamide aryl-centroid and the 4-nitrogen atom of the pyridylpiperazine. Compound 12b was shown to have a greater distance between these functionalities (11.8 A) as compared to the other isomers (9.8-10.4 A). The distance between these two functionalities in 12b was similar to that of a conformer of 11 which has an extended conformation. This suggest that 11 is likely in an extended conformation when bound to the DA D2 receptor. PMID- 7990126 TI - 12th annual symposium on nonhuman primate models for AIDS. Boston, Massachusetts, October 12-15, 1994. Abstracts. PMID- 7990127 TI - Isolation of a peptide antagonist to the thrombin receptor using phage display. AB - The thrombin receptor on platelets is an integral membrane protein and is cleaved by thrombin to expose a "tethered ligand" that binds to and triggers the receptor. Here we have explored the power of phage selection technology to make a peptide antagonist of this receptor using platelets directly for the selection. To focus the selection to the thrombin receptor, we eluted the phage with a peptide agonist of the thrombin receptor. A repertoire (1 x 10(7) phage clones) displaying peptide sequences based on the sequence of the tethered ligand, was constructed and selected by binding to the platelets. After several rounds of selection, we identified phage clones that were able to immunoprecipitate the thrombin receptor from platelets and the encoded peptides were sequenced. This revealed some features in common with the tethered ligand, in particular an arginine residue followed by a proline. Several of the peptides were synthesized chemically and one of the peptides was shown to antagonise platelet aggregation triggered by the agonist peptide, and to inhibit serotonin release and tyrosine phosphorylation triggered by either thrombin or the agonist peptide. Anti aggregatory activity was about ten-fold higher than that of previously reported peptide antagonists of the thrombin receptor. PMID- 7990128 TI - Nuclear magnetic resonance 15N and 1H resonance assignments and global fold of rusticyanin. Insights into the ligation and acid stability of the blue copper site. AB - Nuclear magnetic resonance assignments are reported at pH approximately 3 for a type 1 ("blue") copper protein, rusticyanin, obtained from the acidophilic organism Thiobacillus ferrooxidans. A combination of homonuclear proton and heteronuclear 15N-edited NMR spectra has been used to assign most of the 1H and 15N resonances of reduced rusticyanin. The copper-binding site is shown by analogy with other blue copper proteins to contain the side-chains of Cys138, His143 and Met148 at the C-terminal end of the sequence and a fourth ligand that is most likely a histidine, His85, consistent with the constitution of other type 1 copper sites. The global fold of the molecule is a compact beta-barrel or beta sandwich, which contains a high proportion of beta-sheet secondary structure and a hydrophobic core particularly rich in aromatic residues. The copper-binding active site is surrounded by aromatic residues, and many of the resonances of the residues flanking the active site are shifted to unusual values, consistent with the effects of ring currents. The protected nature of the copper site is demonstrated by the large number of amide protons that are persistent in this region in 99% 2H2O solution at pH 3.4. We suggest that the unusual acid stability, both of the protein itself and of the blue copper active site, is a direct result of the protected and highly hydrophobic nature of the active site sequence and contacting loops and the high proportion of secondary structure in the protein. PMID- 7990129 TI - The molecular replacement solution and X-ray refinement to 2.8 A of a decameric complex of human cyclophilin A with the immunosuppressive drug cyclosporin A. AB - The X-ray structure of a decameric form of a complex of human cyclophilin A (CypA) with the immunosuppressive drug cyclosporin A (CsA) has been determined. The crystals of space group P43212 with cell dimensions a = b = 95.2 A, c = 280.0 A have five copies of the cyclophilin A/cyclosporin A complex in the asymmetric unit. The structure was solved by molecular replacement techniques, using a known cyclophilin A model. Procedures were developed to construct a self-rotation function using the results of cross-rotation searches. The comparison of experimental and constructed self-rotation maps was an important aid in selecting the correct rotation function solution. The translation functions revealed the presence of a cyclic pentamer. A crystallographic dimer axis passes through the non-crystallographic 5-fold rotation axis of the pentameric asymmetric unit, and generates a decameric "sandwich" of CypA/CsA heterodimers that has 52 symmetry. The five CypA/CsA protomers were refined independently using all data to 2.8 A giving a final crystallographic R-factor of 15.7%. Despite the constraints due to the packing arrangement within the decamer, the CypA and CsA conformations are similar to other CypA/CsA structures determined by X-ray crystallography and NMR spectroscopy. The hydrophobic CsA molecules are embedded in the middle of the decameric sandwich with only 20% of their surface exposed to solvent. The binding loop of CsA (residues 1 to 3 and 9 to 11) comprising 42% of the CsA surface, is buried in the peptidyl-prolyl-cis-trans isomerase active site of the cognate binding partner CypA, while the effector loop (residues 4 to 8) packs in the core of the decamer making hydrogen-bonding and van der Waals contacts with three neighbouring molecules. The environment of CsA in the decamer has been analysed and may provide a mimic for the interactions likely to occur between the CypA/CsA complex and its biological target calcineurin. There is no evidence to suggest that the decameric sandwich itself plays a role in immunosuppression by inhibiting calcineurin. However, the chaperone/foldase activity of CypA could require oligomer formation for its biological function. PMID- 7990130 TI - X-ray structure of recombinant ricin A-chain at 1.8 A resolution. AB - Ricin is a potent plant toxin which acts by removing a specific adenine residue from the ribosome. The X-ray crystal structure of a new, tetragonal crystal form of the recombinant ricin A-chain diffracting to 1.8 A resolution has been determined via molecular replacement methods and refined to a crystallographic R factor of 18.6%. The higher resolution electron density allowed improvements to be made upon previously published models, resulting in an increase in the assigned secondary structure of the protein. The enzyme adopts the same global conformation in this crystal form with differences in detail due only partly to crystal packing. The active site superimposes closely with those of previously published models but the locations of the active-site water molecules differ in this structure. To address the current mechanistic model, an additional two structures are presented: recombinant ricin A-chain complexed with the substrate analogue formycin monophosphate as well as with adenosine monophosphate, which is cleaved by the crystalline enzyme. The formycin monophosphate displaces a putative catalytic water molecule. This supports the notion that the analogue does not bind in a transition state conformation and that contacts from other elements of the 28 S RNA natural substrate are required to achieve full reactivity. The structure of the adenosine monophosphate complex suggests a mechanism for the release of the adenine product via of the side-chain Tyr80. The structures suggest that Glu177 is better positioned for the activation of the catalytic water molecule than Arg180. PMID- 7990131 TI - A unique protonated phosphate group in bone mineral not present in synthetic calcium phosphates. Identification by phosphorus-31 solid state NMR spectroscopy. AB - The detailed chemical composition and microstructure of freshly deposited bone mineral, and how these properties change with maturation of the mineral, have been studied intensively and still remain controversial. For example, current analytical technology is inadequate for the unambiguous characterization of the monohydrogen phosphate ions in bone mineral. Using a differential cross polarization/magic angle spinning solid state nuclear magnetic resonance spectroscopy technique, we suppress the dominant orthophosphate (PO4-3) signal to reveal the spectra of the minor phosphate constituents. This method depends upon differences in the cross polarization time constants for phosphorus-31 nuclei in protonated and non-protonated phosphate ions. It is now possible for the first time to directly measure both the proportion of acid phosphate (HPO4-2) as well as the parameters which characterize its isotropic and anisotropic chemical shift. In bone from three species at several developmental stages, we have found a single type of acid phosphate species, identical in all of the specimens examined. The phosphorus-31 isotropic chemical shift of this acid phosphate group in bone mineral corresponds precisely with that of acid phosphate in octacalcium phosphate, and not with that of brushite. In contrast, the bone acid phosphate anisotropic chemical shift parameters are close to those of brushite, and differ significantly from those of octacalcium phosphate. The orthophosphate resonances of bone mineral, synthetic hydroxyapatite and synthetic octacalcium phosphate share identical chemical isotropic shifts, and similar chemical shift anisotropies. The implication of these results is that the intimate structure of the acid phosphate group in bone mineral is unique, and that none of the common synthetic calcium phosphates accounts well for all of the observed solid state phosphorus-31 NMR properties of bone mineral. PMID- 7990132 TI - Stability against denaturation mechanisms in halophilic malate dehydrogenase "adapt" to solvent conditions. AB - Malate dehydrogenase from Haloarcula marisomortui (hMDH) is active, soluble and mildly unstable in an unusually wide range of salt conditions and temperatures, making it a particularly interesting model for the study of solvent effects on protein stability. Its denaturation (loss of activity due to concomitant dissociation and unfolding) kinetics was studied as a function of temperature and concentration of NaCl, potassium phosphate or ammonium sulphate in H2O or 2H2O. A transition-state-theory analysis was applied to the data. In all cases, stability (resistance to denaturation) increased with increasing salt concentration, and when 2H2O replaced H2O. Each salt condition was associated with a particular energy regime that dominated stability. In NaCl/H2O, a positive enthalpy term, delta H not equal to 0, always dominated the activation free energy of denaturation, delta G not equal to 0. In potassium phosphate/H2O and ammonium sulphate/H2O, on the other hand, stability was dominated by a negative activation entropy, delta S not equal to 0. and delta H not equal to 0 changed sign between 10 degrees C and 20 degrees C, consistent with a strong hydrophobic effect contribution, in these salting-out solvents. Decreasing stability at low temperatures, favouring cold denaturation, was observed. Replacing H2O by 2H2O strengthened the hydrophobic effect in all conditions. As a consequence, conditions were found in which hMDH was not halophilic; below 10 degrees C, it was stable in approximately 0.1 M NaCl/2H2O. The solution structure and preferential solvent interactions of hMDH in H2O or 2H2O solvents containing NaCl were studied by densimetry and neutron scattering. Despite the different stability of the protein in H2O or 2H2O, an experimentally identical invariant solution particle was formed in both solvents. It had a total volume of 1.165 cm3 g-1 and bound about 0.4 g of H2O (0.44 g of 2H2O) and about 0.08 g NaCl g protein. The impact of these results on a stabilisation model for hMDH, involving ion binding, is discussed. PMID- 7990133 TI - Analysis and classification of disulphide connectivity in proteins. The entropic effect of cross-linkage. AB - An analysis and a classification of protein disulphide connectivity in a set of distinct sequences are presented. We analyse the number of disulphides per sequence, the number of disulphides per residue and the length of disulphide cross-linked loops. Observed connectivities are classified according to the different possible types of arrangement. In addition, we classify disulphide connectivity by physical models describing the arrangement of multiple disulphides. Firstly, we consider whether the features of native connectivity arrangement are describable by the likelihood of diffusive contact in the unfolded state. This is referred to as the diffusion model, and was originated by Kauzmann. A second model, effectively the inverse of the diffusion model, describes native connectivity arrangement as dominated by the entropic stabilisation effect of cross-linkage. This is referred to as the entropic model. Additionally, we compare the distribution of disulphide cross-linked loops and of loops formed by disulphide-like contacts. For short sequences (less than about 75 residues) native connectivities tend to have entropically more-stabilising arrangement features, whilst for longer sequences (greater than about 200 residues) the diffusion model is appropriate. We introduce the concept of arrangement entropy as a measure of the complexity of a connectivity. PMID- 7990134 TI - Crystallization and preliminary crystallographic data for Rab guanine nucleotide dissociation inhibitor (RabGDI) from bovine brain. AB - X-ray quality crystals of Rab guanine nucleotide dissociation inhibitor (RabGDI) from bovine brain expressed in Escherichia coli have been obtained from 1.73 M ammonium sulfate. The crystals are prismatic long rods and belong to the monoclinic space group P21 with approximate cell dimensions a = 91.9 A, b = 43.5 A, c = 63.2 A, beta = 104.5 degrees and one molecule per asymmetric unit. The crystals are stable in the X-ray beam and diffract to at least 2.3 A. Reverse screening, streak seeding and macroseeding methods were used to obtain and improve the crystals. PMID- 7990135 TI - Transmembrane signaling. Mutational analysis of the cytoplasmic linker region of Taz1-1, a Tar-EnvZ chimeric receptor in Escherichia coli. AB - Taz1-1 is Tar-EnvZ chimeric receptor that is able to induce ompC-lacZ expression in response to aspartate. Previous studies indicated that aspartate binding to the receptor domain of the Taz1-1 receptor modulated the ratio of kinase and phosphatase activities of the cytoplasmic signaling domain. The 80-residue segment of chemoreceptors that is located between the second transmembrane domain and the signaling domain was defined as the linker region. The Taz1-1 chimeric receptor contains 43 amino acid residues of the Tar linker region. In order to understand further the function of the linker region in transmembrane signaling, site-directed random mutagenesis was carried out on the conserved Ala231 in the linker region. Substitution mutations with Val, Glu, Gly, Thr, Lys and His gave the locked "off-mode" form (low ompC-lacZ expression), and substitution mutations with Ile and Leu resulted in the locked "on-mode" form (constitutive ompC-lacZ expression). All the mutant Taz1-1 receptors still retained both OmpR kinase and phospho-OmpR phosphatase activities. Interestingly Taz1N6, a kinase defective mutant, was able to complement with Taz1H1, a phosphatase defective mutant, carrying an off-mode mutant at position 231 to restore Asp-inducible ompC-lacZ expression, but not with Taz1H1 carrying an on-mode mutation. These results suggest that the residue at position 231 in Taz1-1 plays a key role in signal transduction. PMID- 7990136 TI - RNA chain elongation and termination by mammalian RNA polymerase III. Analysis of tRNA gene transcription by imposing a reversible factor-mediated block to elongation using a sequence-specific DNA binding protein. AB - We have used a sequence-specific DNA binding protein to examine transcription elongation and termination by mammalian RNA polymerase III (polIII). The Escherichia coli lac repressor protein, bound to its cognate operator site positioned between the 3' end of the coding region and the termination site of a human tRNA gene, conditionally blocked transcription elongation by polIII in vitro in HeLa cell nuclear extracts. Arrest of elongation by polIII dramatically reduced overall levels of transcription and directed the synthesis of shortened transcripts, consistent with a block to polIII elongation at the boundary of the repressor/DNA complex. Removal of template-bound repressor with the allosteric inducer isopropylthio-beta-D-galactoside (IPTG) allowed extension of nascent transcripts and restored transcriptional activity. Moreover, a subset of transcription complexes were shown to be capable of transcribing through the repressor obstacle. lac repressor positioned just downstream of the natural termination site effected the premature termination of transcription but otherwise had no affect on the overall level of transcription. Our findings demonstrate that elongation and termination by mammalian polIII can be modulated in vitro by a heterologous sequence-specific DNA binding protein. Moreover, the ability to selectivity arrest elongation by polIII at defined positions within the tRNA gene transcription unit has permitted the identification of discrete functional properties of paused mammalian polIII ternary complexes. PMID- 7990137 TI - DNA conformational changes associated with the cooperative binding of cI repressor of bacteriophage lambda to OR. AB - The cI repressor protein (cI) maintains bacteriophage lambda in the lysogenic state in infected Escherichia coli cells by binding cooperatively to three tandemly repeated sequences comprising the right operator (OR). Cooperative interactions occur between alternate pairs of cI dimers bound to adjacent sites. Although crystallographic studies have revealed the structure of the DNA in the 92 amino acid residue amino-terminal fragment-OL1 complex, the structure of the DNA within the OR-cI complex with intact, cooperatively bound cI has not been described. In this study, the structure of the DNA within OR was quantitatively examined using sequence and structure-dependent nuclease cleavage patterns as a function of cI binding. The cooperative binding of cI to OR1 and OR2 induces a conformational change in the DNA of OR3 that is detectable by both DNase I and 5 phenyl-1,10-phenanthroline. Hydroxyl radical footprinting indicates the presence of an "A-tract" between OR1 and OR2 at the site of a run of four adenine-thymine base-pairs, implying a stable bend between the sites of approximately 18 degrees. 5-Phenyl-1,10-phenanthroline footprinting reports conformational changes within the central base-pairs of all three sites that is dependent upon the sequence specific binding of cI. The observed conformational changes are more extensive within OR2 and OR3 compared with OR1, consistent with an "induced-fit" model of sequence-specific recognition. A number of changes in nuclease reactivity within the individual binding sites were quantitatively correlated with cI binding at the other sites within OR. These results demonstrate that changes in the DNA structure are propagated among the sites in response to the binding of cI and imply a role for DNA sequence-dependent conformational changes in the mechanisms of both the intrinsic and cooperative binding reactions of cI to OR. PMID- 7990138 TI - Structural changes of active site cleft and different saccharide binding modes in human lysozyme co-crystallized with hexa-N-acetyl-chitohexaose at pH 4.0. AB - Human lysozyme was co-crystallized with hexa-N-acetyl-chitohexaose, (GlcNAc)6, at pH 4.0 and 4.0 degrees C in a new orthorhombic form, where two protein molecules, MOL1 and MOL2, were contained in an asymmetric unit. The three-dimensional structure was refined to an R-factor of 17.0% at 1.6 A resolution. It was found that (GlcNAc)6 had already been cleaved to (GlcNAc)4 and (GlcNAc)2. In MOL1, (GlcNAc)4 was bound to the A, B, C, and D subsites, and binding sites of (GlcNAc)2 were close to the E and F subsites proposed on the basis of model building by Phillips and his colleagues. In MOL2, only the (GlcNAc)4 moiety could be found in the A, B, C and D subsites. Significant shifts of the backbone atoms were observed in the region of residues 102 to 120, which composed one side of the wall of the active site cleft. Consequently, the active cleft, with respect to the saccharide binding sites A, B and C, is narrower in both protein molecules. The residues 109 to 111 in site D of MOL1 are moved toward saccharide residue D, whereas those of MOL2 are only slightly shifted. In spite of these facts, the saccharide residues in site MOL1 and MOL2 are moved inside of the cleft. The distribution of water molecules and the hydrogen bond network in site D differ between the structures of MOL1 and MOL2. These structural changes in the active site cleft may be responsible for accommodating the substrate and releasing the products of hydrolysis. These results suggest that the three dimensional structures of MOL1 and MOL2 remain in intermediate states between a transition state and an enzyme/product complex state. PMID- 7990139 TI - Structure determination of aquomet porcine hemoglobin at 2.8 A resolution. AB - Considerable attention is currently focused on hemoglobins from lower mammals, such as the pig, for potential use in cell-free blood substitute preparations safe for use in humans. As the first step in the elucidation of structure function relationships in porcine hemoglobin, we have determined the three dimensional structure of aquomet porcine hemoglobin at 2.8 A resolution. Overall, the porcine hemoglobin tetramer is structurally similar to that of human oxyhemoglobin, and the r.m.s. deviation of all backbone atoms (minus five residues at the amino and carboxyl termini of each subunit) is 0.8 A. This similarity is not unexpected given that human and porcine hemoglobins exhibit 85% sequence identity. However, regions of subtle structural differences are implicated in subtle functional differences between the two proteins, such as the 20 to 25% inhibition of the alkaline Bohr effect and the accompanying reduction in oxygen-linked chloride binding observed for porcine hemoglobin. The structural similarity of these two mammalian hemoglobins also rationalizes the novel hybridization behavior of pig and human subunits in transgenic pigs expressing both porcine and human hemoglobins in porcine erythrocytes. PMID- 7990140 TI - Investigating the high affinity and low sequence specificity of calmodulin binding to its targets. AB - Calmodulin (CaM) is a calcium binding protein that regulates a wide range of enzymes. Recently the structures of a number of complexes between CaM and synthetic target peptides have been determined. The peptides correspond to the CaM-binding domain of skeletal and smooth muscle myosin light-chain kinase (MLCK) and calmodulin-dependent protein kinase II alpha. Comparison of the peptide-free and peptide-bound structures reveals that CaM undergoes a large conformational change when forming a complex, resulting in the formation of a binding surface that provides for an optimal interaction with its target. In this work, the available co-ordinates of the NMR solution structure of CaM-skeletal MLCK peptide are used as a basis upon which several molecular models of binding are built. The detailed features of the protein's peptide binding surface are revealed through two-dimensional topographical projections. Negatively charged margins at the binding surface extremities interact strongly with basic peptide residues separated by nine or ten positions. The binding surface core is hydrophobic and displays a groove with four deep pockets, which can accommodate bulky peptide residues at relative positions 4 and 8 (pocket A), 11 (pocket B), 13 (pocket C), 14 and 17 (pocket D). Therefore, both electrostatic and van der Waals' features contribute to the high affinity binding. A search for alternative peptide placements in the binding tunnel reveals the dominant role of specific electrostatic interactions in the binding energy. Apolar interactions are more permissive, such that the hydrophobic side-chains that line the binding tunnel adapt in order to maintain favourable van der Waals' contacts. The model suggests that the structure can accommodate large peptide translations (up to 5 A) and a reversed peptide binding mode, with a little loss in binding interaction energy. These calculations are compared with available experimental data, providing a structural rationale for the low sequence specificity of the CaM target recognition. PMID- 7990141 TI - Structure of protocatechuate 3,4-dioxygenase from Pseudomonas aeruginosa at 2.15 A resolution. AB - Protocatechuate 3,4-dioxygenase catalyzes the aromatic ring cleavage of 3,4 dihydroxybenzoate by incorporating both atoms of molecular oxygen to yield beta carboxy-cis,cis-muconate. The structure of this metalloenzyme from Pseudomonas aeruginosa (now reclassified as P. putida) has been refined to an R-factor of 0.172 to 2.15 A resolution. The structure is a highly symmetric (alpha beta Fe3+)12 aggregate with a root-mean-square (r.m.s.) difference of 0.18 A among symmetry-related atoms. The tertiary structure of the two polypeptides (alpha and beta) are highly homologous (r.m.s. difference of 1.05 A over 127 C alpha atoms), suggesting that the ancestral enzyme was originally a homodimer with two active sites. Indeed, a non-functional, vestigial active site retains many of the properties of the functional active site but does not bind iron. The coordination geometry of the non-heme iron catalytic cofactor can best be described as trigonal bipyramidal with Tyr447 (147 beta) and His462 (162 beta) serving as axial ligands, and Tyr408 (108 beta), His460 (160 beta) and Wat837 serving as equitorial ligands. The active site environment has a number of basic residues that may promote binding of the acidic substrate. Within the putative active site cavity which is located between alpha and beta chains, five approximately coplanar solvent molecules suggest a position for the planar substrate Trp449 (149 beta), Ile491 (191 beta), defined by Gly14 (14 alpha) and Pro15 (15 alpha). In this position the guanidino group of Arg457 (157 beta) would be buried by the substrate, suggesting a functional role in catalysis. PMID- 7990142 TI - Toward a mechanism for the allosteric transition of pig kidney fructose-1,6 bisphosphatase. AB - We examine structural aspects of the allosteric transition of pig kidney fructose 1,6-bisphosphatase (Fru-1,6-Pase) by analyzing the X-ray structures of the R and T form enzymes. The results show a hierarchical structural change during the R to T transition. Upon binding of AMP, a cascade of structural changes occurs starting from the AMP site: expansion of the AMP site, local conformational changes of helices H1 and H2, independent rotations and translation of helices H1, H2 and H3 (and loops connecting them), reorganization of the AMP domain as a whole and its 1.9 degrees rotation relative to the fructose-1,6-bisphosphate domain, and conformational changes at the C1-C2 and C1-C4 interfaces leading to the quaternary conformational change of a 17 degrees rotation between dimers. The AMP inhibition results from the relative movement between the AMP and FBP domains which distorts the active site during the transition by shifting the metal binding sites to unfavourable positions. Communication that ensures cooperativity during R to T transition relies on changes in positions of helices H1, H2 and H3, loops 127-131, 168-170 and 187-192, and on N-terminal residues. All of these features are close to the C1-C4 and symmetry equivalent C2-C3 interfaces and the relatively small C1-C3 interface of the T form. These secondary structures form the framework along which structural changes due to AMP binding can propagate to other parts of the monomers as well as across monomer interfaces. Future dynamics studies may be useful to analyze initiation, propagation and completion of the quaternary conformational change of Fru-1,6-Pase upon AMP binding. Also, site directed mutagenesis experiments are expected to provide more detailed descriptions of the importance of each of the residues that has been identified here in the proposed mechanisms. PMID- 7990143 TI - TEM beta-lactamase mutants hydrolysing third-generation cephalosporins. A kinetic and molecular modelling analysis. AB - The catalytic properties of six "natural" mutants of the TEM-1 beta-lactamase have been studied in detail, with special emphasis on their activity versus third generation cephalosporins. On the basis of the recently determined high resolution structure of the wild-type enzyme, and of the substrates' structures optimized by the AMI quantum chemistry method, we have attempted to explain the influences of the mutations on the substrate profiles of the enzymes. Some of the kinetic results have thus received a satisfactory, semi-quantitative interpretation, especially in the case of single mutations. Analysis of the double mutants proved more hazardous. Extending the comparison to some other class A beta-lactamases showed that similar properties could result from different sequences, supplying an interesting example of convergent evolution within a generally diverging family. PMID- 7990144 TI - Three-dimensional reconstruction from a frozen-hydrated specimen of the chiton Lepidochiton sp. hemocyanin. AB - A frozen-hydrated specimen of the hemocyanin of the chiton Lepidochiton sp. has been subjected to a three-dimensional reconstruction by the random conical tilt- series m wall and a collar complex. The wall is composed of five oblique wall units, disposed as a five-stranded, right-handed helix, separated by five clefts. The oblique wall unit is composed of two strings of functional units separated by a groove parallel with the cleft. The collar complex is a crown-like structure composed of five collar complex units, located at one end of the molecule and slightly protruding outside the cylinder wall. The collar complex unit comprises a collar unit probably composed of two functional units, one of which is connected to the wall, and an arch composed of two additional functional units, each connected to the wall by a narrow bridge. Each arch crosses a cleft between adjacent oblique wall units. The indentations present on both circular faces of the molecule and the dispositions of the masses resemble those of cephalopod hemocyanins. PMID- 7990145 TI - Purification, crystallization and preliminary X-ray diffraction studies of alpha toxin of Clostridium perfringens. AB - Alpha-toxin of Clostridium perfringens, cloned in Escherichia coli, has been purified and crystallized from ammonium sulphate using the hanging drop vapour diffusion method at 20 degrees C. The crystals diffract to a minimum Bragg spacing of 2.7 A, belong to the space group R32 (with a = b = 153.3 A, c = 95.4 A, alpha = beta = 90 degrees and gamma = 120 degrees) and contain a single polypeptide chain in the crystallographic unit. PMID- 7990146 TI - Crystallization and preliminary X-ray diffraction studies on ADP-ribosylation factor 1. AB - ADP-ribosylation factor 1 (ARF-1) is a member of a family of small G-proteins that regulate both intracellular vesicle transport and phospholipase D activity. Crystals of ARF-1 suitable for X-ray diffraction analysis have been grown in the presence of GDP by the hanging drop vapour diffusion method. Crystals grow in space group C2 with cell dimensions a = 122.36 A, b = 45.01 A, c = 91.96 A and beta = 133.62 degrees and diffract to at least 2.3 A resolution. A second crystal form has been characterized (space group C2, a = 69.70 A, b = 45.25 A, c = 60.45 A, beta = 109.6 degrees) but does not grow reproducibly. PMID- 7990147 TI - Crystallization and preliminary X-ray studies of the diphtheria Tox repressor from Corynebacterium diphtheriae. AB - Crystals of the diphtheria tox repressor (DtxR) from Corynebacterium diphtheriae suitable for structure determination have been obtained. DtxR activated with transition metal ions represses the expression of the structural gene for the diphtheria toxin, tox, which is encoded on the genome of a family of closely related corynebacteriophages. The space group of the obtained crystals is trigonal P3(1)21 or its enantiomorph P3(2)21 with a = b = 64.2 A, c = 220.5 A, alpha = beta = 90 degrees, gamma = 120 degrees. Two monomers comprise the asymmetric unit. The crystals diffract to a resolution of better than 3 A. PMID- 7990148 TI - Crystallization and preliminary crystallographic data of recombinant human osteogenic protein-1 (hOP-1). AB - We have obtained trigonal crystals of recombinant human osteogenic protein-1 (hOP 1), a member of the transforming growth factor-beta (TGF-beta) superfamily. hOP-1 (also referred to as BMP-7) is a bone morphogenetic protein and is active as a dimer of M(r) 32 to 36 kDa. The crystals have the symmetry of space group P3(1)21 or the enantiomorph P3(2)21 with unit cell dimensions of a = b = 99.46 A, c = 42.09 A. The crystals diffract to 2.2 A resolution and there is one hOP-1 monomer per asymmetric unit. In this paper we describe the first crystallization of a bone morphogenetic protein and present the results of preliminary X-ray diffraction data from the native protein and two heavy-atom derivatives. PMID- 7990149 TI - Expression, crystallization and preliminary crystallographic analysis of human carbonyl reductase. AB - The cDNA of human placental carbonyl reductase (EC 1.1.1.184), a member of the short-chain dehydrogenase family of enzymes, was introduced into the plasmid vector pET-11a and the enzyme overexpressed in Escherichia coli. Recombinant carbonyl reductase was purified to homogeneity, characterized physically and kinetically, and crystallized for X-ray diffraction study. The recombinant protein was indistinguishable from human tissue carbonyl reductase (CR8.5 form) on the basis of partial sequence analysis, substrate specificity, susceptibility to inhibitors and immunochemical analysis. Similar to the tissue enzyme which which occurs in multiple molecular forms thought to arise from autocatalytic modification by 2-oxocarboxylic acids, a second form of the recombinant enzyme was generated under bacterial growth conditions producing high pyruvate concentrations. Purified recombinant protein, which corresponds to the smallest, most basic tissue form (CR8.5), was crystallized against 20% polyethyleneglycol 6000 in 25 mM 2-(N-morpholino)ethanesulfonic acid buffer (Mes) at pH 6.0 using the hanging drop method. Crystals of human carbonyl reductase diffract to better than 3.0 A, and the diffraction symmetry is consistent with a crystal that belongs to the tetragonal space group P4(1)(3)2(1)2 with unit cell dimensions of a = b = 55 A, c = 175 A, alpha = beta = gamma = 90.0. The asymmetric unit contains one molecule of 30.2 kDa. PMID- 7990150 TI - Characterization by cDNA cloning of two new human protein kinases. Evidence by sequence comparison of a new family of mammalian protein kinases. AB - Two new human cDNAs, designated phclk2 and phclk3, which have a high identity to the cDNA of the human protein kinase clk, were characterized. Typical features of hclk2 and hclk3 proteins are non-homologous N-terminal regions and the presence of the C-terminal protein kinase domain, which is characteristic for serine/threonine-type kinases. We also identified the differentially spliced forms phclk2(139) and phclk3(152) with deletions of 88 and 97 nt, respectively, which lead to changes in the open reading frames. hclk2(139) and hclk3(152) proteins do not possess a protein kinase domain and are nearly identical to the N terminal regions of the above-mentioned protein kinases. We verified that differentially spliced variants also exist for hclk1 as well as for a mouse clk protein kinase. It was shown that shorter and longer alternatively spliced mRNAs co-exist in different human tissues. According to Southern analysis, hclk2 and hclk3 appear to be specified by single copy genes. The genes for hclk2 as well as for hclk3 were localized to human chromosomes 1 and 15, respectively. PMID- 7990151 TI - Indoor radon and lung cancer: risky or not? PMID- 7990152 TI - Nm23--into the basement (membrane) PMID- 7990153 TI - Role for pregnant women in clinical trials debated. PMID- 7990154 TI - Survivors' meeting stresses need for advocacy, activism. PMID- 7990155 TI - Workshop affirms value of breast conserving treatments. PMID- 7990156 TI - States strive to screen hard-to-reach women. PMID- 7990157 TI - Residential radon exposure and lung cancer among nonsmoking women. AB - BACKGROUND: Radon at sufficiently high concentrations is known to cause lung cancer among underground miners and in experimental laboratory animals. PURPOSE: Our aim was to determine whether indoor levels of radon are associated with a detectable increase in lung cancer. Nonsmoking women were selected because they offer the best opportunity to detect radon-related risk while minimizing the potentially confounding influences of cigarette smoking and occupation. METHODS: A population-based, case-control study of incident lung cancer was conducted in Missouri. A total of 538 non-smoking white women diagnosed with lung cancer between 1986 and 1992 and 1183 age-matched control subjects were identified from the Missouri Cancer Registry and from driver's license and Medicare listings, respectively. Information on lung cancer risk factors was obtained by telephone interview. Year-long radon measurements were sought in every dwelling occupied for the previous 5-30 years. RESULTS: Radon measurements covered 78% of the relevant residential period, and women reported being indoors for 84% of this time. The time-weighted average radon concentrations were exactly the same for case subjects and control subjects (1.82 pCi/L of air [pCi L-1]). Radon levels greater than 4 pCi L-1 were experienced by 6.5% of the case subjects and 6.8% of the control subjects. For all data combined, there was little evidence for a trend of lung cancer with increasing radon concentrations (two-tailed trend test, P = .99 continuous data analysis; P = .19 categorical data analysis). A positive dose-response trend was suggested for the adenocarcinoma cell type and among directly interviewed women (two-tailed trend test; P = .31 continuous data analysis; P = .04 categorical data analysis), but not for other histologies or among those who had surrogate interviews. CONCLUSIONS: The possibility of detecting a risk from indoor radon in this study was maximized by (a) including a large number of nonsmoking women with high indoor occupancy, (b) conducting a large number of radon measurements near the time of the diagnosis of cancer, and (c) controlling for known causes of lung cancer. However, an association between lung cancer and the exposure to domestic levels of radon was not convincingly demonstrated. IMPLICATIONS: The magnitude of the lung cancer risk from radon levels commonly found in U.S. dwellings appears low. PMID- 7990159 TI - Growth and chemotherapeutic response of cells in a hollow-fiber in vitro solid tumor model. AB - BACKGROUND: Cancer treatments that appear promising in tissue culture are often less effective in solid tumors, in part because of the proliferative and microenvironmental heterogeneity that develops in these tumors as they grow. Heterogeneous tumor models are thus needed for drug screening. PURPOSE: Our goal was to develop and test for drug evaluation a solid tumor model based on cell growth inside biocompatible hollow fibers. METHODS: Building on the experience of Hollingshead and co-workers with a sparse-cell, hollow-fiber tumor model, we tested six human tumor cell lines for in vitro growth inside 450-microns internal diameter polyvinylidine fluoride fibers and examined them histologically. Human SW620 colon carcinoma cells grown in hollow fibers were also examined using electron microscopy, and their doxorubicin sensitivity was assessed. A colorimetric assay based on sulforhodamine B was adopted to replace the more cumbersome clonogenic cell survival assay. RESULTS: Five of the human tumor cell lines tested grew to confluence, forming heterogeneous in vitro tumors with subpopulations of viable and necrotic cells. For SW620 hollow-fiber tumors, maximum viable cell populations in excess of 10(8) cells/mL were obtained after 8 days of growth. This viable cell density remained roughly constant for 3-4 days, permitting dose-response experiments over this time interval. Tumor cells in hollow fibers were much more resistant to a 4-hour doxorubicin exposure than were tumor cells in monolayers: LC50 values (i.e., the drug concentrations at which the plating efficiency equals one-half the plating efficiency of untreated cells) of 3.5 microM and 0.16 microM were obtained for hollow-fiber tumors and monolayers, respectively. LC50 values decreased when drug exposure time was increased. Results from the colorimetric assay were in agreement with those from the clonogenic assay. CONCLUSION: The successful growth of tumor cells to confluence in hollow fibers and the feasibility of performing in vitro drug dose response experiments with a relatively easy colorimetric assay demonstrate the potential of the hollow-fiber solid tumor model as a tool for experimental therapeutic research. IMPLICATION: Hollow-fiber solid tumors may prove useful for experimental drug evaluation. PMID- 7990158 TI - A novel function for the nm23-H1 gene: overexpression in human breast carcinoma cells leads to the formation of basement membrane and growth arrest. AB - BACKGROUND: We have developed a culture system using reconstituted basement membrane components in which normal human mammary epithelial cells exhibit several aspects of the development and differentiation process, including formation of acinar-like structures, production and basal deposition of basement membrane components, and production and apical secretion of sialomucins. Cell lines and cultures from human breast carcinomas failed to recapitulate this process. The data indicate the importance of cellular interactions with the basement membrane in the regulation of normal breast differentiation and, potentially, its loss in neoplasia. PURPOSE: Our purpose was to use this assay to investigate the role of the putative metastasis suppressor gene nm23-H1 in mammary development and differentiation. METHODS: The metastatic human breast carcinoma cell line MDA-MB-435, clones transfected with a control pCMVBamneo vector, and clones transfected with pCMVBamneo vector containing nm23-H1 complementary DNA (the latter of which exhibited a substantial reduction in spontaneous metastatic potential in vivo) were cultured within a reconstituted basement membrane. Clones were examined for formation of acinus-like spheres, deposition of basement membrane components, production of sialomucin, polarization, and growth arrest. RESULTS: In contrast to the parental cell line and control transfectants, MDA-MB-435 breast carcinoma cells overexpressing Nm23 H1 protein regained several aspects of the normal phenotype within reconstituted basement membrane. Nm23-H1 protein-positive cells formed organized acinus-like spheres, deposited the basement membrane components type IV collagen and, to some extent, laminin to the outside of the spheres, expressed sialomucin, and growth arrested. Growth arrest of Nm23-H1 protein-positive cells was preceded by and correlated with formation of a basement membrane, suggesting a causal relationship. CONCLUSION: The data indicate a previously unidentified cause-and effect relationship between nm23-H1 gene expression and morphological biosynthetic-growth aspects of breast differentiation in this model system. IMPLICATIONS: While the basement membrane microenvironment is capable of directing the differentiation of normal human breast cells, neoplastic transformation abrogates this relationship, suggesting that intrinsic cellular events are also critical to this process. The data identify nm23-H1 gene expression as one of these events, suggesting an important role in the modulation of cellular responsiveness to the microenvironment. The data also identify previously unknown growth inhibitory effects of nm23-H1 gene overexpression. PMID- 7990160 TI - Use of the Kohonen self-organizing map to study the mechanisms of action of chemotherapeutic agents. AB - BACKGROUND: Many natural and synthetic compounds might prove to be effective in cancer chemotherapy. To identify potentially useful agents, the National Cancer Institute screens over 10,000 compounds annually against a panel of 60 distinct human tumor cell lines in vitro. This screening program generates large amounts of data that are organized into relational databases. Important questions concern the information content of the data and ways to extract that information. Previously, statistical techniques have revealed that compounds with similar patterns of activity against the 60 cell lines are often similar in structure and mechanism of action. Feed-forward, back-propagation neural networks have been trained on this type of data to predict broadly defined mechanisms of action of chemotherapeutic agents. PURPOSE AND METHOD: In this report, we examine the information that can be extracted from the screening data by means of another type of neural network paradigm, the Kohonen self-organizing map. This is a topology-preserving function, obtained by unsupervised learning, that nonlinearly projects the high-dimensional activity patterns into two dimensions. Our dataset is almost identical to that used in the earlier neural network study. RESULTS: The self-organizing maps we constructed have several important characteristics. 1) They partition the two-dimensional array into distinct regions, each of which is principally occupied by agents having the same broadly defined mechanism of action. 2) These regions can be resolved into distinct subregions that conform to plausible submechanisms and chemically defined subgroups of submechanism. 3) These results (and exceptions to them) are consistent with those obtained with the use of such deterministic measures of similarity among activity patterns as the Euclidean distance or Pearson correlation coefficient. CONCLUSIONS: Our results indicate that the activity patterns obtained from the screen contain detailed information about mechanism of action and its basis in chemical structure. The self-organizing map can be used to suggest the mechanism of action of compounds identified by the screen as potentially useful chemotherapeutic agents and to probe the biology of the cell lines in the cancer screen. Kohonen self-organizing maps, unlike the previously applied neural networks, preserve and reveal the relationships among compounds acting by similar mechanisms and therefore have the potential to identify compounds that act by novel cytotoxic mechanisms. PMID- 7990161 TI - Familial clustering of breast and prostate cancers and risk of postmenopausal breast cancer. AB - BACKGROUND: Previous studies have suggested that cancers of the breast and prostate cluster in families and that the presence of both diseases in a family may be associated with increased risk of breast cancer. PURPOSE: Our purpose was to evaluate whether 1) prostate cancer aggregates in families with postmenopausal breast cancer, 2) families with cancers of the breast and prostate are the same ones as families with cancers of the breast and ovary, and 3) a family history of prostate cancer is associated with increased risk of postmenopausal breast cancer. METHODS: We analyzed data from a large prospective cohort study of Iowa women that were (at baseline) aged 55-69 years in 1986. At the third follow-up survey in 1992, self-reported data on family history of breast, ovarian, and prostate cancers in parents and siblings were provided by 30,883 women. Additional information was collected to ascertain whether the age-of-onset of breast cancer in mothers or sisters was before or after the age of 45 years. Cancer occurrence was documented using the State Health Registry of Iowa. RESULTS: History of prostate cancer in their father or a brother was reported by 3384 (11.0%) of the women, and a total of 4090 women (13.2%) reported breast cancer in their mother or a sister. A positive family history of both cancers was reported by 556 women, significantly (two-sided P < .001) greater than the 457 women expected if the family histories were independent. The aggregation of breast, prostate, and ovarian cancers was reported by 22 participants, greater than the 2.7 expected (two-sided P < .0001). During 6 years of follow-up, 578 breast cancers were identified in the cohort at risk. Compared with women without a family history of either cancer, women with a family history of breast cancer had a relative risk (RR) of 1.37 (95% confidence interval [CI] = 1.06-1.79) if the affected relative had onset after the age of 45 years, and an RR of 1.71 (95% CI = 1.13-2.61) if the affected relative had onset at or before the age of 45. A family history of prostate cancer in the absence of a family history of breast cancer was associated with an RR of 1.19 (95% CI = .90-1.56). However, a family history of both breast and prostate cancers was associated with RRs of 2.06 (95% CI = 1.23-3.45) and 2.35 (95% CI = .97-5.67) for breast cancer onset in relatives of greater than 45 and less than or equal to 45 years, respectively. CONCLUSIONS: These observations are concordant with recent reports that suggest a shared familial risk (inherited or environmental) for these hormone-dependent malignancies. PMID- 7990163 TI - Serum albumin, bilirubin, and uric acid and the anatomic site-specific incidence of colon cancer. PMID- 7990162 TI - p53 gene expression in node-positive breast cancer: relationship to DNA ploidy and prognosis. PMID- 7990164 TI - More on endometrial cancer and tamoxifen. PMID- 7990165 TI - More on endometrial cancer and tamoxifen. PMID- 7990166 TI - More on misclassification of nasopharyngeal cancer. PMID- 7990167 TI - Carbofuran toxicity. AB - Carbofuran, an anticholinesterase carbamate, is commonly used as an insecticide, nematicide, and acaricide in agricultural practice throughout the world. Due to its widespread use in agriculture, contamination of food, water, and air has become imminent, and consequently adverse health effects are inevitable in humans, animals, wildlife, and fish. Currently, carbofuran's involvement is most frequently encountered in malicious poisoning. The literature on chemical properties, acute toxicity data, poisoning incidences, pharmacokinetics, and mechanism of toxicity of carbofuran is briefly reviewed. Much emphasis is given to the metabolism of carbofuran, and the impact of carbofuran and its two major metabolites (3-hydroxycarbofuran and 3-ketocarbofuran) on overall toxicity. Biochemical (cholinergic and noncholinergic), hematological, and immunological effects induced by carbofuran are discussed in detail. Carbofuran and/or its major metabolites can cross the placental barrier and produce serious effects on the maternal-placental-fetal unit. Carbofuran's toxicity can be potentiated by simultaneous exposure with other cholinesterase inhibitors. Literature on various biomarkers of carbofuran exposure and on induced adverse health effects is also presented. To date, a combination of atropine and memantine remains the most effective antidotal treatment against acute carbofuran toxicity. PMID- 7990168 TI - Responses of vascular smooth muscle cells to toxic insult: cellular and molecular perspectives for environmental toxicants. AB - Over the past several decades emphasis has been given to the elucidation of mechanisms involved in the onset and progression of cardiovascular disorders. Stroke, hypertension, and atherosclerosis continue to rank as primary causes of death in the western world. In the case of atherosclerosis, the preferential localization of atheroma to large- and medium-sized blood vessels and the sequence of events leading to plaque development have been well defined. Damage to luminal endothelial and/or medial smooth muscle cells, migration of inflammatory cells, diffusion or local delivery of mediators within the vessel wall, proliferation of vascular smooth muscle cells, and cellular accumulation of lipids are now recognized as hallmarks of the pathologic process. Although these events have been established with a fair degree of certainty, the mechanisms responsible for initiation of the atherosclerotic process are not yet completely understood. Environmental chemicals have come under increasing scrutiny as evidence continues to accumulate suggesting that toxic insult plays an important role in the initiation and/or progression of atherosclerotic disorders. This review focuses on various aspects of xenobiotic-induced vascular injury with emphasis on the toxic effects of allylamine and benzo[a]pyrene in smooth muscle cells, the primary cellular component of atherosclerotic lesions. Both of these chemicals modulate growth and differentiation programs in aortic smooth muscle cells and have been implicated in the development of atherosclerotic-like lesions in laboratory animals. The major findings from recent studies examining the cellular and molecular basis of toxicant-induced phenotypic modulation of vascular smooth muscle cells to a proliferative state and the role of oxidative metabolism, phospholipid turnover, protein kinase C, ras-related signal transduction, and matrix interactions in the vasculotoxic response to allylamine and benzo[a]pyrene are discussed. PMID- 7990170 TI - PCB congeners in the rat brain: selective accumulation and lack of regionalization. AB - Perturbations in the developing nervous system have been associated with perinatal exposures to polychlorinated biphenyls (PCBs). It remains unclear whether these neurotoxic effects are direct or secondary to other toxic processes. This study was designed to determine which PCB congeners accumulate in the brain as a result of perinatal exposure and if this accumulation is regionally specific. Sprague-Dawley rat dams were dosed by gavage with corn oil or Aroclor 1242 in corn oil (4 or 16 mg/kg/d) on d 10-16 of gestation. At weaning (d 21), one male and one female pup from each litter were euthanatized and three specific regions of the brain (frontal cortex, hippocampus, and caudate putamen) were collected for PCB analysis by gas chromatography. Ten peaks, which represent 10-14 PCB congeners, were detected in all samples. There were no differences in PCB concentration between sexes or among brain regions, but the different congeners differed from each other in degree of bioaccumulation. Brain PCB concentrations increased with increased dose for all congeners except PCB 28 (2,4,4'), which was present at a higher concentration in the lower dose-group. To characterize regionalization of PCBs in the brain further, weanling rats were dosed intravenously with [14C]-PCB 77 (3,3',4,4'-tetrachlorobiphenyl; 0.25 microCi/g; 2.0 micrograms/g) or [14C]-PCB 47 (2,2',4,4'-tetrachhlorobiphenyl; 0.25 microCi/g; 5.3 micrograms/g) in dimethyl sulfoxide (DMSO). Rats were killed after 72 h and the brains were quickly removed and frozen on dry ice. The brains were serially sectioned on a cryostat and the sections (16 microns) subjected to autoradiography (3-5 mo of exposure). The radioactivity was homogeneously distributed in the brain tissue for both PCBs. PCB 77-treated, but not PCB 47 treated, pups showed increased activity in areas with blood vessels present. This was consistent with differences in the blood-brain ratios for PCB 47 and PCB 77, which were determined to be 0.44 and 16.8, respectively. PMID- 7990169 TI - Immunocytochemical evidence for a nuclear and a cytoplasmic O6-methylguanine repair mechanism in cultured rat hepatocytes. AB - The localization of DNA and RNA adducts was studied at the ultrastructural level using antibodies directed against O6-metG and the protein A-gold technique. Primary rat hepatocyte cultures were exposed for 2-24 h to 5 mM N nitrosodimethylamine (NDMA) or 0.1 mM N-methyl-N'-nitro-N-nitrosoguanidine (MNNG). In both cases, the O6-metG immunoreactive sites were concentrated in the nucleus and in the rough endoplasmic reticulum (RER) rich cytoplasmic regions. The highest gold labeling density measured was observed at 2 h of NDMA or MNNG treatment. However, after a 24-h exposure, very little labeling was observed in both the nuclear and the cytoplasmic compartments. The rate of disappearance of immunoreactive sites was faster in the cytoplasm than in the nucleus, Untreated control preparations showed no specific immunogold labeling. Furthermore, when cells were exposed first to NDMA and MNNG for a few hours and then to culture medium containing no genotoxin, and subsequently were reexposed to NDMA or MNNG for a few hours, very little labeling of both the nuclear and cytoplasmic compartments was observed. Control preparations without a second genotoxin exposure showed a normal labeling pattern. Control preparations without genotoxin showed no gold labeling. Our results provide evidence for the existence of a cytoplasmic O6-metG repair mechanism that behaves like its nuclear counterpart. PMID- 7990171 TI - Time-dependent effects of o-xylene on rat lung and liver microsomal membrane structure and function. AB - The present study investigates the time-dependent effect of acute intraperitoneal o-xylene administration (1 g/kg) on rat hepatic and pulmonary mixed-function oxidase (MFO) content and activity and microsomal membrane structural parameters for up to 12 h postadministration. The purpose of this study was to determine whether o-xylene has similar effects on these parameters as those previously observed for the m and p isomers. o-xylene decreased total pulmonary cytochrome P 450 content and aryl hydrocarbon hydroxylase (AHH) activity at all time points examined with maximal inhibition occurring at 3 h postdose. The isozyme-specific MFO activity responsible for AHH activity was examined using benzyloxyresorufin O dealkylation (BROD) as a measure of CYP2B1 activity and ethoxyresorufin O dealkylation (EROD) as a measure of CYP1A1 activity. Reduced pulmonary activity for both EROD and BROD was noted for the 12-h postexposure period, in agreement with the decreases in total cytochrome P-450 content and AHH activity data. In contrast, increased hepatic cytochrome P-450 content was noted at 6 and 12 h with slightly increased EROD activity and markedly increased BROD activity. Conjugated diene (CD) formation, and index of membrane peroxidation, and phospholipid (PL) and cholesterol (CL) content of the microsomal membranes were also examined in lung and liver to assess membrane structural integrity. Pulmonary CD formation was increased only at the 12-h time point, while hepatic CD formation was increased from 3 to 12 h. An increase in pulmonary microsomal PL and CL content was noted as early as 1 h postdose. In liver, PL content was increased as early as 3 h, with no change in CL content. An increase in the PL/CL ratio, suggesting an increase in membrane fluidity, was observed in pulmonary microsomes 12 h after dosing, and in hepatic microsomes at 3, 6, and 12 h postdose. There was no correlation between solvent tissue levels and MFO or membrane changes. It seems unlikely that the lipid changes are causal in the observed o-xylene-induced MFO alterations, since they precede membrane lipid changes. Further, MFO activity decreases in lung and increases in liver, whereas lipid parameters increase in both organs. While these data may indicate an organ-selective difference in the relationship between membrane lipid changes and MFO activity, it is more likely that these lipid changes represent alternate toxicological effects of o-xylene. The results of this study indicate that the metabolism of other xenobiotics may be altered in o-xylene-exposed individuals in an organ-selective fashion. PMID- 7990172 TI - Tissue distribution and elimination of indium in male Fischer 344 rats following oral and intratracheal administration of indium phosphide. AB - The use of indium phosphide (InP) in the semiconductor industry has raised concerns about potential occupational exposure. The tissue distribution and elimination of indium were investigated in adult male Fischer 344 rats following either a single or 14 consecutive daily oral doses, or following an intratracheal instillation of InP (10 mg/kg). The concentrations of indium ions in blood, urine, feces, and tissues were quantified either using direct acid digestion followed by electrothermal atomic absorption spectrophotometry (ET-AAS) or using an extraction method with methyltricapryl ammonium ions to remove indium from the matrix followed by ET-AAS. Indium was poorly absorbed from the gastrointestinal tract in both single and multiple oral dose studies. Upon its absorption, indium was relatively evenly distributed among the major organs such as liver, kidney, lung, spleen, and testes. By 96 h after oral dose treatment, less than 0.11% of the dose of indium was recovered from tissues in the single- or multiple-dose experiment. At 96 h, retention of indium in the body was about 0.36% of the dose (except for lung) following intratracheal instillation of InP. Following oral dose administration, the majority of indium was recovered from the gastrointestinal tract and its contents. The high recovery of indium (73% of the dose) in the feces after intratracheal instillation presumably reflects mucociliary clearance and/or biliary excretion of indium. Urinary indium accounted only for 0.08-0.23% of the dose during a 240-h collection period in both single- and multiple-dose studies. It seems that fecal excretion serves as the major route for indium elimination, and this results from poor absorption. Because of the poor absorption of indium following multiple oral doses or intratracheal instillation of InP, it seems unlikely that indium will accumulate in the body following InP exposure. PMID- 7990173 TI - Experimental design for parameter estimation through sensitivity analysis. AB - Parameter estimates can be obtained by fitting a numerical simulation model to experimental data, but these estimates may be biased and/or imprecise because of noise in the experimental data. Appropriate choice of experimental conditions, such as exposure or substrate concentrations and sampling times, can minimize the effect of experimental noise on parameter estimates, thus reducing bias and improving precision. This article describes a technique for selecting experimental (initial) conditions and measurement times for optimal parameter estimation. The technique makes use of a user-supplied mathematical simulation model for the process under study with a set of "current" parameter values specified. These "current" parameter values are the best that can be obtained using all available experimental data and/or literature information at the time when design calculations are performed. Early in a modeling study, the "current" parameter values will be tentative--based on a relatively small amount of information. Later in a study, the "current" parameter values may be known to reasonable accuracy, but final confirmation is desired. The technique uses the simulation model to calculate a numerical index for each possible experimental design. The numerical index, or Information Index, is a measure of the response of a simulation model to changes in parameter values, described by Kalogerakis and Luus (1983, 1984). The experimental design with the greatest value of Information Index is the one under which parameters can be most precisely estimated. Computation of the Information Index, described in detail, can be somewhat complicated, depending on the software available. The results, however, are simple to interpret and provide valuable information on the quality of alternate proposed experiments. The technique is applicable to a broad range of dynamical systems. Its use is demonstrated by application to a simulation model being developed to describe the in vitro metabolism of benzene by mouse liver microsomes. PMID- 7990175 TI - Diagnosis of early postoperative carotid artery thrombosis determined by transcranial Doppler scanning. PMID- 7990174 TI - Catheter-induced bilateral internal carotid artery occlusion. AB - A case of acute occlusion of both internal carotid arteries is presented where the precipitating cause appears to be catheter manipulation during angiography. Timely surgical intervention reversed the neurologic deficit. PMID- 7990176 TI - Increased preoperative endothelin release in patients with vascular disease. PMID- 7990177 TI - Reinforced aortic anastomosis after infrarenal abdominal aortic aneurysm resection. PMID- 7990178 TI - Foscarnet: a possible cause of ulnar artery thrombosis in a patient with AIDS. PMID- 7990179 TI - Transluminally placed endovascular stented grafts and their impact on vascular surgery. PMID- 7990180 TI - Peripheral vascular surgery with magnetic resonance angiography as the sole preoperative imaging modality. AB - PURPOSE: Magnetic resonance angiography (MRA) is a developing technique that provides arteriograms without the risks associated with iodinated contrast and arterial puncture or the expense of hospitalization. Prior reports have demonstrated the accuracy of peripheral vessel MRA for evaluation of the aorta through pedal vessels. This study sought to determine whether vascular reconstructions could be planned and accomplished on the basis of MRA alone. METHODS: Eighty consecutive candidates for bypass with ischemic rest pain or tissue loss were studied with preoperative outpatient MRA of the juxtarenal aorta through the foot. Confirmation of MRA findings was provided by intraoperative intraarterial pressure measurements for proximal vessels and postbypass arteriography for the runoff. Life-table analysis of graft patency and limb salvage was performed. RESULTS: Two patients could not tolerate MRA and required contrast arteriography, but all others underwent reconstructive procedures on the basis of MRA alone (11 aortobifemoral, 67 infrainguinal). Intraoperative findings regarding suitability of inflow and outflow vessels confirmed the accuracy of the MRAs in every case. MRA indicated that none of the patients undergoing infrainguinal bypass had significant inflow occlusive disease, and this was confirmed at operation with pressure measurements of inflow vessels that were always within 10 mm Hg (peak systolic) of systemic pressure. The results of intraoperative completion arteriography and preoperative MRAs were identical for all but two patients who had minor discrepancies. All aortobifemoral reconstructions remained patent, and all limbs remained intact. The infrainguinal reconstructions had an 84% limb salvage rate and 78% primary graft patency rate at 21 months. Comparison of charges for patients undergoing preoperative MRA versus contrast angiography showed a cost savings of $1288 for each patient treated with preoperative MRA alone. CONCLUSIONS: MRA is a noninvasive, cost effective outpatient imaging technique that, if properly performed and interpreted, is sufficient for planning peripheral bypass procedures. Its use may supplant contrast arteriography in many patients. PMID- 7990181 TI - The significance of calf muscle pump function in venous ulceration. AB - PURPOSE: Patients with clinically evident chronic venous insufficiency were evaluated to relate the degree of insufficiency and calf muscle pump dysfunction to venous ulceration. METHODS: Sixty-nine limbs in 55 patients with chronic venous insufficiency by Society for Vascular Surgery/International Society for Cardiovascular Surgery Classification were compared in three groups: classes 1 and 2 with no history of ulceration (19 limbs); class 3 with healed ulceration (20 limbs); and class 3 with active ulcers (30 limbs). Air plethysmography measurements of outflow fraction, venous volume, venous filling time, venous filling index, ejection fraction, ejection volume, residual volume fraction, and residual volume were made. In 62 of the 69 limbs, color-flow duplex ultrasonography was used to determine the pattern of reflux. RESULTS: The outflow fraction was normal in 84%, 75%, and 77% of nonulcerated, healed, and ulcerated limbs. The venous filling index was abnormal in most limbs (nonulcerated 95%, healed 90%, ulcerated 98%) but not significantly different among groups. Differences in calf muscle pump function were significant. Ulcerated limbs had significantly poorer ejection fractions (p = 0.0002) and greater residual volume fractions (p = 0.0006) than nonulcerated or healed limbs. By ultrasonography, deep and superficial vein incompetence was present in most limbs and was not statistically different among groups. Although venous insufficiency was not measurably different among groups, limbs with active venous ulcers had significantly poorer calf muscle pump function than those with healed ulcers or with no history of ulceration. CONCLUSION: Venous insufficiency is necessary but not sufficient to cause ulceration, and a deficiency of the calf muscle pump is significant to the severity of venous ulceration. PMID- 7990182 TI - Presentation and patterns of aortic aneurysms in young patients. AB - PURPOSE: Although aortic aneurysm (AA) is primarily a disease of older age groups, younger (< 51 years) patients infrequently are admitted requiring AA surgery. We sought to compare the characteristics of these patients with those of a randomly selected group of older patients with AA. METHODS: We identified 26 patients with AA (group I) under age 51 (mean age 44.8) treated surgically between 1977 and 1993, after excluding patients with acute aortic dissection, traumatic pseudoaneurysms, and ascending or arch aneurysms, and compared them with 75 randomly selected patients with AA between the ages of 65 and 75 (mean age 70.3) who were surgically treated during the same time period (group II). RESULTS: Prevalence of hypertension, diabetes, coexisting heart, kidney, or occlusive peripheral vascular disease was similar between the two groups, and familial aneurysm rates and sex distribution did not differ significantly. More patients in group I had symptoms at the time of presentation (46% vs 6.7%, p < 0.001), and they also had larger AAs (6.9 cm vs 6.0 cm, p = 0.01). Definable causes of aneurysmal disease, such as Takayasu's, Cogan's, and Marfan syndromes, were more common among the young patients (23% vs 0%, p = 0.01), but most (77%) young patients did not have an identifiable syndrome associated with their aneurysm disease. Group I had a marked shift toward proximal aneurysms, defined as involvement of juxtarenal, suprarenal, or thoracoabdominal aorta (46% vs 18% in group II, p < 0.01). This difference persisted even when aneurysms associated with the above syndromes were excluded from consideration (p = 0.02). Cigarette smoking was much more common among the young patients (83% vs 51% in group II, p < 0.01). Smoking in group II was associated with more extensive aneurysm disease (p = 0.04). CONCLUSIONS: Aneurysmal disease presenting in the young adult is more likely to be symptomatic and associated with more proximal aortic involvement than aneurysmal disease in older patients. Smoking appears to play an important role in the pathogenesis of aneurysmal disease in the young patient and was associated in our study with more proximal aneurysms among older patients. A subgroup of patients at risk for early and aggressive aneurysm disease is suggested by these data. PMID- 7990183 TI - Can the deep femoral artery be used reliably as an inflow source for infrainguinal reconstruction? Long-term results in 563 procedures. AB - PURPOSE: Historically, most infrainguinal bypasses originated from the common femoral artery. In spite of sporadic reports of the use of the deep femoral artery as an inflow source, its durability has not been critically reviewed. METHODS: From 1977 to 1994, 2829 infrainguinal reconstructions have been performed. Of these, 563 (20%) procedures have been performed with the deep femoral artery used as the inflow source. The indication for operation was limb salvage in 91.5% of cases. Four hundred eleven procedures were performed with use of the saphenous vein in situ, 48 were performed with partial in situ vein, and 75 were performed with excised (translocated) vein (29 other). When the deep femoral artery was relatively disease free, it was accessed through a lateral or standard inguinal approach. Reasons given for the use of the deep femoral artery were inadequate vein length, concomitant inflow procedures, prior groin dissections, and occluded superficial femoral artery. RESULTS: The 1- and 5-year secondary patency rates for all bypasses with the deep femoral artery were 90.4% and 76.9%, respectively, as compared with 88% and 73.3% for common femoral artery based bypasses. Sixty-five patients (11.5%) had concomitant inflow procedures. All patients were monitored with serial noninvasive examinations, and data were collected from the vascular registry. Only eight patients (1.6%) required further inflow reconstructions for salvage of bypasses. CONCLUSIONS: The hemodynamically unobstructed deep femoral artery is a reliable and durable inflow source for patients requiring infrainguinal bypasses. Its patency rates are comparable to those of the common femoral artery-based reconstructions in our experience. PMID- 7990184 TI - Comparison of basilic vein and polytetrafluoroethylene for brachial arteriovenous fistula. AB - PURPOSE: The aim of this study was to compare patency and complication rates between basilic vein and polytetrafluoroethylene (PTFE) for brachial arteriovenous fistulas (AVF) for long-term hemodialysis. METHODS: All basilic vein and PTFE brachial AVF constructed between March 1988 and April 1993 were retrospectively reviewed. After construction of life-tables, log-rank testing was used to compare the primary patency rate of basilic vein AVF (n = 59) with the primary and secondary patency rates of PTFE AVF (n = 47). Complication rates were calculated for each type of fistula and compared by use of chi-squared testing. RESULTS: The primary patency rate for basilic vein AVF (90%) was superior to that of PTFE AVF (70%) at 1 year (p < 0.01), and at 2 years (86% vs 49%, p < 0.001). Complications occurred two and a half times more frequently in the PTFE group than in the basilic vein group (p < 0.05). CONCLUSIONS: Basilic vein AVF provided superior patency rates and lower complication rates compared with PTFE AVF. Prospective randomized trials comparing the two fistula types is required to firmly establish the basilic vein AVF as the alternative access procedure of choice after a failed or unconstructable radiocephalic fistula. PMID- 7990185 TI - Retroperitoneal hematoma after cardiac catheterization: prevalence, risk factors, and optimal management. AB - PURPOSE: Retroperitoneal hematoma is an unusual, but potentially serious, complication after cardiac catheterization. The predisposing factors, typical presentation, and clinical course of this iatrogenic complication are identified, and the role of surgery in its treatment is defined. METHODS: A retrospective review of 9585 femoral artery catheterizations over a 5-year period allowed identification and evaluation of all patients with retroperitoneal hemorrhage. RESULTS: Retroperitoneal hematoma developed in 45 patients (overall prevalence 0.5%), with the highest frequency after coronary artery stenting (3%). In the group of patients who underwent coronary artery stenting, statistically significant predictors of this complication included protocol for sheath removal, female sex, nadir platelet count, and excessive anticoagulation. Signs and symptoms included suprainguinal tenderness and fullness in 100%, severe back and lower quadrant pain in 64%, and femoral neuropathy in 36%. Most patients were treated successfully with transfusion alone. Seven patients (16%) required operation; in four, hypotension unresponsive to volume resuscitation developed early after catheterization; and, in three, a progressive fall in hematocrit level led to surgery 24 to 72 hours after catheterization. CONCLUSIONS: Retroperitoneal hematoma after cardiac catheterization can usually be treated by transfusion alone. A small subset of patients who have development of hypotension unresponsive to volume resuscitation require urgent operation. PMID- 7990186 TI - Influence of sex on the results of abdominal aortic aneurysm repair. Canadian Society for Vascular Surgery Aneurysm Study Group. AB - PURPOSE: The purpose of this study is to determine the effect of sex on the survival rate and complications after repair of nonruptured and ruptured abdominal aortic aneurysms (AAA). METHODS: The Canadian Society for Vascular Surgery Aneurysm Registry formed the database for analysis and provided current, ongoing follow-up of the patients. Statistical methods included t tests, chi squared analysis, Kaplan-Meier analysis, and Cox regression analysis. RESULTS: Of the 679 patients undergoing repair of a nonruptured AAA, 19.7% were women and 82.3% men. The following risk factors were significantly different (p < 0.05) in women and men: women were older; more had never smoked; more had a positive family history of AAA; fewer had an electrocardiogram showing evidence of an old myocardial infarction; more had coexisting aortoiliac occlusive disease; fewer had popliteal or femoral aneurysms; and the average size of the AAA was smaller. In spite of potential differences in risk, the in-hospital mortality rates were not affected by sex: 5.2% mortality rate for women and 4.4% for men. Early and late vascular complications occurred with a similar prevalence. The late survival rates were not different in women and men: for women, the 1-, 3-, and 5-year cumulative survival rates were 93.0%, 74.2%, and 63.3%, respectively, and for men 90.3%, 82.8%, and 68.9%. To control for the potential effects of other confounding variables on survival, the Cox proportional hazards method was used. When sex was included in a model along with other significant predictive variables of late survival, sex was not found to be a significant predictor of late results. Of the 146 patients with a ruptured AAA, 13.7% were women and 83.3% men. The in-hospital mortality rates were not significantly different: 55.0% for women and 49.2% for men. There was no difference between the cumulative survival rates: the 3- and 5-year survival rates for women were 36.0% and 9.0%, respectively, and for men 33.9% and 26.9%. CONCLUSIONS: Sex was not found to have an effect on the early or late results after repair of nonruptured or ruptured AAA. However, a literature review suggests the possibility of a gender bias in the diagnosis and/or selection of patients for surgical treatment because the proportion of women in surgical series is generally less than the proportion determined from autopsy studies, ultrasound studies, hospital discharge data, and national mortality information. PMID- 7990187 TI - Acute arterial thrombosis associated with total knee arthroplasty. AB - PURPOSE: Acute arterial thrombosis associated with total knee arthroplasty (TKA) is a rare but limb-threatening complication. The purpose of this report was to determine the incidence and optimal management of these complications by reviewing our extensive orthopedic experience and the English-language literature. METHODS: Between April 1989 and March 1994 seven (0.17%) patients had development of acute limb-threatening ischemia after 4097 TKAs that were performed at our hospital. Management of these complications included (1) emergency arteriography to define inflow and outflow arteries, (2) use of autologous vein from the contralateral leg when arterial bypasses were necessary (because TKAs are associated with a high incidence of deep vein thrombosis), and (3) early, aggressive revascularization that often required difficult distal bypasses to achieve limb salvage. Management of our cases are compared with treatment of 13 patients described in the literature. RESULTS: Ten patients treated at other hospitals by arterial thrombectomy alone (six cases), sympathectomy alone (two cases), fasciotomy alone (one case) or delayed arterial bypass resulted in seven major amputations and one death. All seven of our patients and three patients treated elsewhere underwent emergency femorodistal bypasses (six tibial, three below-knee popliteal, one pedal). All 10 patients had limb salvage after long-term follow-up (average 18 months; range 1 to 58). CONCLUSION: Thrombectomy alone for acute arterial thrombosis associated with TKA generally is unsuccessful and associated with unacceptably high amputation rates. Dismal results without emergency bypass is due to underlying chronic occlusive atherosclerotic disease found in these patients and intimal plaque disruption that can occur with knee manipulation or tourniquet compression. Acute arterial occlusion after TKA is best managed by emergency arteriography and a femoroinfrageniculate bypass. PMID- 7990188 TI - Combined vitamin B6 plus folic acid therapy in young patients with arteriosclerosis and hyperhomocysteinemia. AB - PURPOSE: Hyperhomocysteinemia is associated with arteriosclerotic and thromboembolic events. The homocysteine-lowering effect of combined treatment with vitamin B6 plus folic acid has never been explored in a large group of patients with vascular disease. Therefore we studied the effects of at least 6 weeks treatment with these vitamins in 72 patients with cardiovascular disease and mild hyperhomocysteinemia (defined as an increase of the plasma homocysteine level after methionine loading greater than 97.5 percentile of age-matched control subjects but less than 200 mumol/L). METHODS: The existence of mild hyperhomocysteinemia was investigated in 309 consecutive patients under 50 years of age with peripheral arterial occlusive disease, cerebral arterial occlusive disease, or coronary artery occlusive disease. All patients with an abnormal loading test result were treated with vitamin B6, 250 mg daily, plus folic acid, 5 mg daily. After 6 weeks of treatment a second methionine loading test was performed to assess the homocysteine-lowering effect. RESULTS: Mild hyperhomocysteinemia was detected in 72 patients (23%), 33 (46%) of whom also had hyperhomocysteinemia when fasting. Treatment with vitamin B6 plus folic acid normalized the postload plasma homocysteine concentration in 66 of the 72 patients (92%), whereas fasting hyperhomocysteinemia was normalized in 30 of 33 (91%) patients. In six patients therapy failed to achieve normalization of the postload homocysteine levels. In three of these patients, the same treatment was continued for an additional 6 weeks, and in the remaining three patients betaine was added to the treatment regimen. After 6 weeks of additional treatment all six patients had normal postload plasma homocysteine concentrations. CONCLUSION: The prevalence of mild hyperhomocysteinemia in young patients with arterial occlusive disease is high. Simple and inexpensive therapy with vitamin B6 plus folic acid will normalize homocysteine metabolism, as assessed by the homocysteine plasma level after methionine loading, in virtually all these patients. PMID- 7990190 TI - Superficial femoral vein: a useful autogenous harvest site. AB - PURPOSE: The purpose of this study was to present the use of superficial femoral vein (SFV) as an arterial bypass graft when ipsilateral saphenous vein is inadequate. METHODS: Data collected prospectively were reviewed on 24 patients (25 limbs) who had an arterial bypass with SFV performed by the authors between January 1, 1988, and December 31, 1991. Many anatomic sites are represented. The indication for operation was gangrene in six patients, severe rest pain or ulceration in 11, mild to moderate rest pain in six, and graft infection in two. There had been 42 previous reconstructions in these 25 limbs. RESULTS: There has been surprisingly little long-term disability from removal of the SFV. Immediately after surgery four limbs developed acute venous congestion that resolved quickly. Twenty percent of the patients with patent grafts have continued to wear a pressure gradient stocking for swelling 1 year after surgery, one patient requires additional pressure to control induration. All grafts were patent at 30 days. During a mean follow-up of 2 years, three grafts have required revision, and three have occluded. Stenosis did not develop at valve sites or in the body of the SFV portion of any of these grafts. There were two deaths from heart-related causes in the first 30 days after operation. Life-table analysis for the whole group shows a primary patency rate of 66% (SE 10.3%) and an assisted patency rate of 80% (SE 8.7%) at 2 years. CONCLUSIONS: SFV harvest is well tolerated, even in the absence of ipsilateral saphenous vein. The magnitude of the operation is greater than saphenous vein harvest but yields a thick-walled vein of excellent diameter with many applications as an autogenous conduit, particularly where a large-diameter graft is indicated. PMID- 7990189 TI - Upper extremity arterial injuries: experience at the Royal Adelaide Hospital, 1969 to 1991. AB - PURPOSE: A review of upper extremity arterial injuries managed at the Royal Adelaide Hospital between 1969 and 1991 was undertaken because the optimal management of complex upper extremity trauma, particularly in proximal injuries, remains unclear. METHODS: Patients were identified from the computer registry of patients treated by the vascular unit at the Royal Adelaide Hospital. They were studied in three groups: (1) subclavian and axillary artery, (2) brachial artery, and (3) radial and ulnar artery injuries. The mechanism of injury, associated injuries, treatment and outcome were reviewed. RESULTS: There were 114 patients with upper extremity arterial injuries: 28 with subclavian and axillary, 62 with brachial, and 24 with radial and ulnar artery injuries. Good upper limb function was obtained in 32% of subclavian and axillary artery injuries, 79% of brachial artery injuries, and all radial and ulnar artery injuries. Amputation was performed in 14% of the proximal injuries and 8% of the brachial artery injuries. Three deaths occurred in this study group. CONCLUSION: Blunt proximal injuries were usually associated with neurologic, soft tissue, and bony damage, which was responsible for the poor functional outcome. Critical limb ischemia or severe hemorrhage rarely occurred. Complete brachial plexus lesions resulted in uniformly poor outcomes. More distal injuries were associated with fewer nerve and soft tissue injuries, resulting in a more satisfactory outcome. PMID- 7990191 TI - Superficial venous insufficiency: correlation of anatomic extent of reflux with clinical symptoms and signs. AB - PURPOSE: The aim of this study was to assess the distribution and extent of valvular incompetence in patients with reflux confined to the superficial venous system and correlate the extent of such reflux with clinical symptoms and signs. METHODS: Two hundred fifty-five limbs of 217 patients with superficial venous insufficiency and normal perforating and deep veins were examined with color-flow duplex imaging. One hundred twenty-three limbs (48.2%) of 102 patients had reflux confined to the long saphenous system, 83 limbs (32.6%) of 72 patients had reflux confined to the the short saphenous system, and 49 limbs (19.2%) of 43 patients had reflux in both long and short saphenous systems. RESULTS: In the long saphenous system the commonest pattern of reflux was that which extended throughout the length of long saphenous vein (LSV) (47%). Ache, swelling, and skin changes were common in the presence of below knee reflux irrespective whether the thigh segment was involved. Ulceration (8%) was found only in limbs with reflux extending throughout the length of LSV. In the short saphenous system the most common pattern of reflux extended throughout the length of short saphenous vein (SSV) (57%) without involvement of Giacomini or gastrocnemial veins. Ache and swelling were present in 62% and 72% of the limbs, but this incidence was not related to the extent of reflux. Swelling, skin changes, and ulceration occurred only when the whole of the SSV was involved. In the limbs with reflux in both the long and short saphenous systems, the most common pattern of reflux extended throughout the length of both systems (45%). In these limbs the incidence of swelling was 80%. The incidence of skin changes went from 44% when the below-knee segment of the LSV was involved to 73% when reflux occurred throughout the LSV and SSV. Ulceration (14%) was found only in the latter situation. Variable patterns of saphenogastrocnemial termination were seen. In 57.8% of the limbs SSV joined the popliteal vein just above the popliteal crease, whereas the SSV terminated in the thigh in 26.6%. CONCLUSIONS: We conclude that ache, ankle edema, and skin changes in limbs with reflux confined to the superficial venous system are predominantly associated with reflux in the below knee veins. Ulceration is found only when the whole of the LSV is involved (8%) or when reflux is extensive in both LSV and SSV (14%). PMID- 7990192 TI - Sex difference in the mechanical properties of the abdominal aorta in human beings. AB - PURPOSE: A previous study has shown age- and sex-related differences in abdominal aortic compliance. In that study blood pressure determined by auscultation in the brachial artery was assumed to be equal to blood pressure in the abdominal aorta. To validate our findings we investigated the pressure-diameter (P-D) relationship of the abdominal aorta. METHODS: Diameter and pulsatile diameter change of the abdominal aorta were determined noninvasively by an ultrasound phase-locked echo tracking system with simultaneous measurement of aortic pressure resulting in P-D curves in 27 healthy male and female volunteers 23 to 72 years of age. The degree of error in aortic compliance as calculated from blood pressure determined by auscultation of the brachial artery rather than from direct measurement of aortic pressure was evaluated. Compliance was defined as the inverse of pressure strain elastic modulus (Ep) or of stiffness (beta). RESULTS: There was no significant difference in the systolic pressure at the two sites, but the diastolic pressure was systematically overestimated by approximately 10 mm Hg when determined by the auscultatory method (p < 0.01) leading to a 15% to 20% underestimation of Ep and stiffness (beta). The individual P-D curves exhibited hysteresis, were nonlinear, and revealed that the aorta is more distensible at lower than at higher pressures. The steepness of the P-D curve decreased with increasing age and this occurred at an earlier age in men than in women. CONCLUSION: This investigation demonstrates a decrease in abdominal aortic wall distensibility with age, which occurs at an earlier age in men, and confirms earlier results by use of the indexes Ep and stiffness (beta). This implies that the abdominal aorta in men is more prone to degenerative changes, which may be one of the factors responsible for the sex difference in aortic vascular disease. PMID- 7990193 TI - Invaginated axial saphenectomy by a semirigid stripper: perforate-invaginate stripping. AB - PURPOSE: This study was designed to evaluate a recently introduced form of stripping of primary varicose veins by the technique of perforate-invaginate (PIN) stripping. METHODS: One hundred twelve consecutive limbs presenting with 91 long and 21 short saphenous varicosities displaying saphenofemoral or saphenopopliteal junctional escapes with varying length of greater or lesser saphenous (axial) reflux underwent operation in 1 year. All surgeries were performed in an office setting with the patient receiving locoregional anesthetic with use of the invaginated PIN stripping in conjunction with tributary hook-stab avulsion. RESULTS: In the 112 procedures performed, there were no tract hematomas or dysesthesias caused by nerve damage. Postoperative morbidity was nonexistent, permitting all patients to resume normal daily occupational and sporting activities immediately. CONCLUSIONS: PIN stripping is an excellent method of invagination stripping. There is a minimal likelihood of vein tearing. Compared with conventional ankle-to-groin (or popliteal fossa) stripping, PIN stripping is minimally invasive, does not cause damage to structures around the vein, does not require convalescence, eliminates the need for a lengthy distal second incision, can be performed in an office setting with the patient receiving locoregional anesthetic, and is most cost-efficient. PMID- 7990194 TI - Popliteal vascular compression in a normal population. AB - PURPOSE: Positional popliteal artery obstruction is believed to be an important factor contributing to popliteal artery entrapment syndromes. This study was undertaken to define the positional anatomy and physiologic condition of the vessels in the popliteal fossa in groups of highly trained and normally active young men and women. We postulate that at least some symptom-free individuals can occlude the popliteal artery with leg positioning. METHODS: Seventy-two limbs were evaluated in 36 subjects. Symptom-free subjects were recruited in four groups: normally active men, normally active women, male competitive runners, and female competitive runners. All subjects underwent noninvasive testing that included resting segmental limb pressures and Doppler waveforms and color-flow duplex imaging with the leg in the neutral position and then with knee extension with active and passive dorsiflexion and plantar flexion of the foot. Subjects unable to occlude the popliteal artery with positioning were then exercised, and studies were repeated. Magnetic resonance imaging, with magnetic resonance angiography, was conducted on 14 subjects, with each leg studied in the neutral position and with active positioning. RESULTS: Positional popliteal arterial occlusion occurred in 38 of 72 limbs (53%). No intergroup comparisons were statistically significant. The response of each leg was symmetric in 89% of subjects. No subject who could not occlude the popliteal artery at rest was able to do so with exercise. Magnetic resonance imaging disclosed normal anatomy in all subjects and showed the location of popliteal occlusion to be at the level of the soleal sling, with positional compression by the soleus muscle, the lateral head of the gastrocnemius, the plantaris, and popliteus muscles. CONCLUSION: Popliteal arterial occlusion can be induced in 53% of subjects with simple leg positioning caused by myofascial compression. This must be considered when evaluating patients for intervention on the basis of physiologic testing of the popliteal vessels. PMID- 7990195 TI - Intravenous leiomyomatosis. AB - Intravenous leiomyomatosis is a rare tumor in which benign smooth muscle cells grow into the pelvic venous channels of female patients. A case of intravenous leiomyomatosis with cardiac extension in a 45-year-old woman is described. The patient was diagnosed with cardiac syncope 3 months after total abdominal hysterectomy and was successfully treated with a two-stage approach consisting of sternotomy followed by laparotomy. The cause, disease, presentation, diagnosis, treatment and recurrence are reviewed. PMID- 7990196 TI - Persistent hypoglossal artery: diagnostic and therapeutic considerations concerning carotid thromboendarterectomy. AB - Fetal anastomotic connections between the developing internal carotid and basilar arterial systems are via the three presegmental arteries: the otic artery, the hypoglossal artery, and the trigeminal artery. After formation of the posterior communicating artery from the caudal branch of the internal carotid artery, the presegmental arteries are generally obliterated. Rarely, however, these primitive carotid-basilar anastomoses will persist into adult life, and may be detected as incidental findings at the time of cerebral angiography during evaluation of the patient with suspected cerebrovascular disease. In addition, persistence of such anastomoses may result in the coexistence of anterior and posterior circulation symptoms, precipitating diagnostic confusion. Two patients with symptoms and persistent hypoglossal artery undergoing carotid thromboendarterectomy are discussed, with emphasis on clinical presentation, diagnostic criteria and intraoperative management. PMID- 7990197 TI - Born in the USA: infant health paradox. PMID- 7990198 TI - Medical team seeks to identify human remains from mass graves of war in former Yugoslavia. PMID- 7990199 TI - Time for new head, new approach at OAM. PMID- 7990200 TI - Vaccinia-based immunization may be on the way. PMID- 7990201 TI - From the Food and Drug Administration. PMID- 7990202 TI - From the Centers for Disease Control and Prevention. Update: trends in AIDS diagnosis and reporting under the expanded surveillance definition for adolescents and adults--United States, 1993. PMID- 7990203 TI - From the Centers for Disease Control and Prevention. Update: influenza activity- United States, 1994-95 season. PMID- 7990204 TI - Varying carbohydrate intake in NIDDM. PMID- 7990205 TI - Varying carbohydrate intake in NIDDM. PMID- 7990206 TI - Varying carbohydrate intake in NIDDM. PMID- 7990207 TI - Race and access to erythropoietin by patients on hemodialysis. PMID- 7990208 TI - Nosocomial bloodstream infections in the critically ill. PMID- 7990209 TI - Changes in adiposity associated with pregnancy. PMID- 7990210 TI - Changes in adiposity associated with pregnancy. PMID- 7990211 TI - Let's stop boxing in the Olympics and the US military. PMID- 7990212 TI - Let's stop boxing in the Olympics and the US military. PMID- 7990213 TI - Formalin therapy for radiation proctitis. PMID- 7990214 TI - Thyroid hormone use and bone mineral density. PMID- 7990215 TI - Isolated visual symptoms in an older women. PMID- 7990216 TI - Smoking, alcohol, and neuromuscular and physical function of older women. Study of Osteoporotic Fractures Research Group. AB - OBJECTIVE: To determine the associations of current and lifetime smoking and alcohol use with physical function in an older population. DESIGN: Survey. SETTING: Four clinic centers in the United States. PARTICIPANTS: A total of 9704 community-dwelling, ambulatory white women 65 years or older recruited from four areas of the United States. MAIN OUTCOME MEASURES: Twelve performance tests of muscle strength, agility and coordination, gait and balance, and self-reported functional status. RESULTS: Compared with women who never smoked, current smokers had significantly poorer function on all of the performance measures except grip strength after adjusting for age, history of stroke, body mass index, clinic site, physical activity, and alcohol use (P < .05). This decrease in function was 50% to 100% as great as that associated with a 5-year increase in age, and most measures worsened with increasing numbers of pack-years. Compared with current moderate drinkers, nondrinkers had significantly poorer function on all of the performance measures except tandem walk (P < .05). Evaluation of a dose effect with alcohol was limited by the small number of heavy drinkers in the study. CONCLUSIONS: In this population, women who currently smoke are weaker and have poorer balance and poorer performance on measures of integrated physical function than nonsmokers. Smoking is associated with a decline in physical function. Current moderate drinkers have better physical function compared with nondrinkers, but associations of function with heavy drinkers could not be assessed. PMID- 7990217 TI - The cost-effectiveness of voluntary counseling and testing of hospital inpatients for HIV infection. AB - OBJECTIVE: To evaluate the cost-effectiveness of voluntary counseling and testing of US hospital inpatients for the human immunodeficiency virus (HIV). DATA SOURCES: Data for entry into the model were derived from a review of the literature, consultation with experts, and consensus of the authors. DATA EXTRACTION: We rated our confidence in these probabilities and costs by grading the data inputs using methods adapted from those of the US Preventive Services Task Force. DATA SYNTHESIS: Decision analysis models were developed to evaluate two outcomes: (1) cost per health care worker (HCW) HIV infection averted if measures are taken by the HCW to reduce his or her risk of acquiring HIV; and (2) cost per inpatient HIV infection detected. Sensitivity analyses were also conducted. Using baseline input values, testing to avert HCW infection may prevent 3.6 HIV infections per year at a total program cost of $2.7 billion, or a cost of $753 million per infection averted. At baseline assumptions (seroprevalence = 1%), testing to detect inpatient HIV infection would cost $16,104 per year per infection detected. Cost-effectiveness at baseline drops to $8353 per HIV infection detected if the seroprevalence is 10%. If testing is limited to hospitals with inpatient seroprevalences of at least 1%, approximately 5400 persons per year will be falsely labeled HIV-positive. CONCLUSIONS: This analysis provides no justification for testing inpatients to prevent HIV infection of HCWs. Screening inpatients to detect HIV infection may be justified at seroprevalences exceeding 1%, but issues of medical or social discrimination, false-positive results, informed consent, and logistics must be resolved first. PMID- 7990218 TI - The impact of serious illness on patients' families. SUPPORT Investigators. Study to Understand Prognoses and Preferences for Outcomes and Risks of Treatment. AB - OBJECTIVE: To examine the impact of illness on the families of seriously ill adults and to determine the correlates of adverse economic impact. DESIGN: Data were collected during the Study to Understand Prognoses and Preferences for Outcomes and Risks of Treatment (SUPPORT), a prospective cohort study of outcomes, preferences, and decision making in seriously ill hospitalized adults and their families. SETTING: Five tertiary care hospitals in the United States. PARTICIPANTS: The 2661 seriously ill patients in nine diagnostic categories who survived their index hospitalization and were discharged home were eligible for this analysis. Surrogate and/or patient interviews about the impact of illness on the family were obtained for 2129 (80%) of these patients (mean age, 62 years; 43% women; 6-month survival, 75%). OUTCOME MEASURES: Surrogates and patients were surveyed to determine the frequency of adverse caregiving and economic burdens. Multivariable analyses were performed to determine correlates of loss of family savings. RESULTS: One third (34%) of patients required considerable caregiving assistance from a family member. In 20% of cases, a family member had to quit work or make another major life change to provide care for the patient. Loss of most or all of the family savings was reported by 31% of families, whereas 29% reported loss of the major source of income. Patient factors independently associated with loss of the family's savings on multivariable analysis included poor functional status (odds ratio [OR], 1.40; 95% confidence interval [CI], 1.10 to 1.78 for patients needing assistance with three or more activities of daily living), lower family income (OR, 1.74; 95% CI, 1.37 to 2.21 for those with annual incomes below $25,000), and young age (OR, 2.85; 95% CI, 2.13 to 3.82 for those younger than 45 years compared with those 65 years or older). CONCLUSIONS: Many families of seriously ill patients experience severe caregiving and financial burdens. Families of younger, poorer, and more functionally dependent patients are most likely to report loss of most or all of the family's savings. PMID- 7990219 TI - Association of acetaminophen hepatotoxicity with fasting and ethanol use. AB - OBJECTIVES: To evaluate the association of fasting and alcohol use with hepatotoxicity from acetaminophen ingested for therapeutic reasons. DESIGN: Retrospective case series. SETTING: Hospitals of the University of Pittsburgh (Pa) Medical Center. PATIENTS: A total of 126,779 discharge summaries from January 1987 to July 1993 were reviewed using a comprehensive, whole-text-indexed medical database to identify all patients with acetaminophen ingestion and hepatotoxicity. These patients were categorized according to the intended acetaminophen use and dose of acetaminophen ingested. MAIN OUTCOMES MEASURED: The independent variables of chronic alcohol use, recent alcohol use, and recent fasting were determined for all patients. RESULTS: Forty-nine patients with acetaminophen hepatotoxicity (aspartate aminotransferase > 1000 U/L) were identified. Twenty-one patients (43%) ingested acetaminophen for therapeutic purposes. All patients with hepatotoxicity took more than the recommended limit of 4 g/d. Recent fasting was more common than recent alcohol use among those who suffered hepatotoxicity after a dose of 4 to 10 g of acetaminophen per day (P = .02). Recent alcohol use was more common in the group who took more than 10 g/d than in those who took 4 to 10 g/d (P = .004). CONCLUSION: Acetaminophen hepatotoxicity after a dose of 4 to 10 g/d was associated with fasting and less commonly with alcohol use. Patients who developed hepatoxicity after taking acetaminophen doses of greater than 10 g/d for therapeutic purposes were alcohol users. Acetaminophen hepatotoxicity after an overdose appears to be enhanced by fasting in addition to alcohol ingestion. PMID- 7990220 TI - Birth after preimplantation diagnosis of the cystic fibrosis delta F508 mutation by polymerase chain reaction in human embryos resulting from intracytoplasmic sperm injection with epididymal sperm. AB - Men with congenital bilateral absence of the vas deferens (CBAVD) have been regarded as presenting a mild form of cystic fibrosis (CF). In this article, we report a case of male-factor infertility, in which both partners are carriers of the delta F508 mutation and the male partner has CBAVD. Microsurgical epididymal sperm aspiration (MESA) was performed to obtain spermatozoa; intracytoplasmic sperm injection (ICSI) was carried out on the oocytes since the motility of the spermatozoa was severely impaired; and embryo biopsy and a polymerase chain reaction (PCR) were carried out for preimplantation diagnosis of the CF delta F508 mutation. Single-blastomere analysis was performed and indicated that two embryos were affected (homozygous delta F508) and three embryos were carriers. After transfer of the latter three embryos, a singleton pregnancy was established. At amniocentesis, the delta F508 carrier status of the fetus with a 46, XY karyotype was confirmed. A healthy boy was born and the presence of vasa deferentia, bilaterally, was confirmed. The CF sweat test was also normal. Successful fertilization can be obtained by combination of MESA and ICSI in patients with CBAVD. Preimplantation diagnosis of CF is indicated. Pregnancy and birth of normal children can ensue in such patients. PMID- 7990221 TI - Disputes between medical supervisors and trainees. Council on Ethical and Judicial Affairs, American Medical Association. PMID- 7990222 TI - Adverse reactions to over-the-counter analgesics taken for therapeutic purposes. PMID- 7990223 TI - Making medical errors into "medical treasures''. PMID- 7990224 TI - Coping with calamity. How well does health care disaster planning work? PMID- 7990225 TI - New trends aimed at healing by design. PMID- 7990226 TI - Exhibit explores link between art and epilepsy. PMID- 7990227 TI - Ruling on physician role in prisoner executions. PMID- 7990228 TI - From the Health Care Financing Administration. PMID- 7990229 TI - From the Centers for Disease Control and Prevention. Hantavirus pulmonary syndrome--Virginia, 1993. PMID- 7990230 TI - From the Centers for Disease Control and Prevention. Update: alcohol-related traffic fatalities--United States, 1982-1993. PMID- 7990231 TI - From the Centers for Disease Control and Prevention. Prevalence of self-reported epilepsy--United States, 1986-1990. PMID- 7990232 TI - Tacrine for Alzheimer's disease. PMID- 7990233 TI - Tacrine for Alzheimer's disease. PMID- 7990234 TI - Tacrine for Alzheimer's disease. PMID- 7990235 TI - Computer networks as a medical resource. PMID- 7990236 TI - The Italian pertussis vaccine trial: ethical issues. PMID- 7990237 TI - Workforce planning: estimating emergency physicians and uncovering primary care. PMID- 7990238 TI - Workforce planning: estimating emergency physicians and uncovering primary care. PMID- 7990239 TI - Tetanus immunization in adults. PMID- 7990240 TI - Defining sepsis. PMID- 7990241 TI - Costs vs quality in different types of primary care settings. AB - OBJECTIVE: To determine the relationship between efficiency in use of resources and quality of care provided by physicians serving as the usual source of care for patients in a state Medicaid program. DESIGN: Retrospective quality-of-care review of 2024 outpatient medical records of 135 providers sampled from system wide Medicaid claims data in Maryland. SUBJECTS: Providers in three types of practice settings (hospital outpatient clinic, community health center, and physician's office) were stratified into three case mix-adjusted resource use groups (high, medium, and low). A sample of patients with the diagnoses of diabetes, hypertension, asthma, well-child care, or otitis media were identified from Medicaid claims forms from visits during 1988. Case mix was controlled by the application of the ambulatory care groups, a method that characterizes populations according to their burden of morbidity. MAIN OUTCOME MEASURES: Nurses from the local peer review organization audited medical records using explicit criteria for quality of care in several categories: evidence of impaired access, evidence of compromised technical quality, evidence of inappropriate care, outcome of care, and several generic indicators of quality. Well-adult care was assessed for patients with the adult diagnoses. RESULTS: Although there were some systematic differences by type of facility in some aspects of quality of care (more access problems for patients in hospital clinics and more technical quality problems for patients in office-based practice), there were no consistent differences in quality of care overall for patients in different types of settings and no consistent relationships between cost-efficiency and quality of care. However, patients in medium-cost community health centers had the best or second best scores for most of the 21 comparisons of type of quality assessed. CONCLUSIONS: Quality of care provided for common conditions in primary care is not associated with costs generated by providers. Policies directed toward the choice of low-cost vs high-cost providers will not necessarily lead to a deterioration in the quality of care. States can both improve quality and lower costs by consistent monitoring of programs over time. The finding of generally higher quality of care for patients in medium-cost community health centers deserves further study. PMID- 7990242 TI - Effects of high-intensity strength training on multiple risk factors for osteoporotic fractures. A randomized controlled trial. AB - OBJECTIVE: To determine how multiple risk factors for osteoporotic fractures could be modified by high-intensity strength training exercises in postmenopausal women. DESIGN: Randomized controlled trial of 1-year duration. SETTING: Exercise laboratory at Tufts University, Boston, Mass. POPULATION: Forty postmenopausal white women, 50 to 70 years of age, participated in the study; 39 women completed the study. The subjects were sedentary and estrogen-deplete. INTERVENTIONS: High intensity strength training exercises 2 days per week using five different exercises (n = 20) vs untreated controls (n = 19). MAIN OUTCOME MEASURES: Dual energy x-ray absorptiometry for bone status, one repetition maximum for muscle strength, 24-hour urinary creatinine for muscle mass, and backward tandem walk for dynamic balance. RESULTS: Femoral neck bone mineral density and lumbar spine bone mineral density increased by 0.005 +/- 0.039 g/cm2 (0.9% +/- 4.5%) (mean +/- SD) and 0.009 +/- 0.033 g/cm2 (1.0% +/- 3.6%), respectively, in the strength trained women and decreased by -0.022 +/- 0.035 g/cm2 (-2.5% +/- 3.8%) and -0.019 +/- 0.035 g/cm2 (-1.8% +/- 3.5%), respectively, in the controls (P = .02 and .04). Total body bone mineral content was preserved in the strength-trained women (+2.0 +/- 68 g; 0.0% +/- 3.0%) and tended to decrease in the controls (-33+77 g; 1.2% +/- 3.4%, P = .12). Muscle mass, muscle strength, and dynamic balance increased in the strength-trained women and decreased in the controls (P = .03 to < .001). CONCLUSIONS: High-intensity strength training exercises are an effective and feasible means to preserve bone density while improving muscle mass, strength, and balance in postmenopausal women. PMID- 7990243 TI - Survival and disease progression according to gender of patients with HIV infection. The Terry Beirn Community Programs for Clinical Research on AIDS. AB - OBJECTIVE: To compare disease progression and mortality between women and men infected with human immunodeficiency virus (HIV). DESIGN: Multicenter cohort. SETTING: Seventeen community-based centers participating in the Terry Beirn Community Programs for Clinical Research on AIDS (CPCRA). PATIENTS: A total of 768 women and 3779 men enrolled in one or more of 11 protocols between September 7, 1990, and September 30, 1993. MAIN OUTCOME MEASURES: Survival and opportunistic events. RESULTS: The median CD4+ cell count at enrollment into the cohort was 0.240 x 10(9)/L (240/microL) for women and 0.137 x 10(9)/L for men (P < .001). Compared with men, women were younger (36 vs 38 years), more likely to be African American or Hispanic (78% vs 44%), and more likely to have reported a history of injection drug use (49% vs 27%). Women had been followed up for a median of 14.5 months and men for 15.5 months. The adjusted relative risk (RR) for death among women compared with men was 1.33 (95% confidence interval [CI], 1.06 to 1.67; P = .01) and for disease progression (including death) was 0.97 (95% CI, 0.82 to 1.15; P = .72). Women were at increased risk for bacterial pneumonia (RR, 1.38; 95% CI, 1.05 to 1.92) and at reduced risk for the development of Kaposi's sarcoma (RR, 0.16; 95% CI, 0.04 to 0.65) and oral hairy leukoplakia (RR, 0.54; 95% CI, 0.31 to 0.94). The increased risk of death and bacterial pneumonia for women compared with men was primarily evident among those with a history of injection drug use (RR, 1.68 for death, 95% CI, 1.20 to 2.35, P = .003; RR, 1.53 for bacterial pneumonia, 95% CI, 1.03 to 2.29, P = .04). Among patients without a history of disease progression at entry, death was the first event reported for more women than men (27.5% vs 12.2%). CONCLUSIONS: Compared with men, HIV-infected women in the CPCRA were at increased risk of death but not disease progression. Risks of most incident opportunistic diseases were similar for women and men; however, women were at an increased risk of bacterial pneumonia. These findings may reflect differential access to health care and standard treatments or different socioeconomic status and social support for women compared with men. PMID- 7990245 TI - A proposal for structured reporting of randomized controlled trials. The Standards of Reporting Trials Group. PMID- 7990244 TI - A cost analysis of topical drug regimens for dermatophyte infections. AB - OBJECTIVE: To examine the extra cost of using higher-priced drugs as initial therapy for dermatophyte infections, because the many available effective drugs vary considerably in cost. DESIGN: Cost analysis from the purchaser's perspective, comparing two prototypical regimens to treat tinea pedis: one in which all patients initially receive a lower-priced drug and those with unresponsive infections receive a higher-priced drug at a follow-up office visit, and one in which all patients receive the higher-priced drug from the outset. The reference drug was miconazole, an imidazole available without a prescription, for which reported overall efficacy rates are 70% to 100%. MAIN OUTCOME MEASURES: The threshold efficacy rate (the efficacy rate of miconazole below which it is always less expensive to use a specific higher-priced drug first) and the extra cost (of beginning therapy with a higher-priced drug). RESULTS: Assuming the Medicare approved charge for a follow-up visit ($21.98), it is less expensive to begin therapy with a prescription drug only if the efficacy rate of miconazole is less than 55%; this threshold efficacy rate varied from 26% (for a $0 total cost of the follow-up visit) to 79% (for an $89 total cost of the follow-up visit). If the efficacy rate of miconazole is 70%, the extra cost per patient for all patients to receive the least expensive prescription antifungal drug instead of miconazole first was $15.23 and $8.64 if total visit costs were $0 and $21.98; miconazole remained the less expensive alternative as long as the total cost of the follow-up visit was less than $50.76. CONCLUSION: For reported efficacy rates and standard costs of a follow-up office visit, using miconazole first and then treating only those patients with unresponsive infections with a higher-priced prescription drug is less expensive than treating all patients with the higher priced drug. PMID- 7990247 TI - Scalp involvement in dermatomyositis. Often overlooked or misdiagnosed. AB - OBJECTIVE: To characterize scalp involvement in patients with dermatomyositis. DESIGN: Case series. PATIENTS: All patients with dermatomyositis seen in our office between 1988 and mid 1993. Patient inclusion in this study required fulfillment of three or more of Bohan and Peter's criteria for dermatomyositis. RESULTS: Of 17 patients with the diagnosis of dermatomyositis, scalp involvement was present in 14. Five of the 14 patients with scalp involvement were diagnosed as having scalp psoriasis or seborrheic dermatitis before progression of their disease or tissue examination revealed the diagnosis of dermatomyositis. In all patients, the scalp involvement was manifested as atrophic, erythematous, scaly plaques. In addition, alopecia was noted in six of the 14 patients. Treatment of cutaneous involvement included sun avoidance, topical corticosteroids and/or antimalarials, and/or methotrexate. CONCLUSIONS: Recognition of this process is important because scalp involvement is often overlooked, may be misdiagnosed initially, and can be the presenting complaint in some patients with dermatomyositis. PMID- 7990246 TI - Hypertension in the elderly. Implications and generalizability of randomized trials. AB - OBJECTIVE: To estimate morbidity and mortality benefits of drug therapy for hypertensive elderly subjects, compare these benefits with effects in younger subjects, and provide a framework for generalizing results derived from trials to actual patients. DATA SOURCES: A literature search using MEDLINE from 1966 to 1993, references from reviews and trial articles, and experts. STUDY SELECTION: Randomized trials lasting at least 1 year that evaluated effects of drug treatment on morbidity and mortality outcomes in hypertensive persons. DATA EXTRACTION: Four independent reviewers appraised protocol characteristics and quality of selected trials. DATA SYNTHESIS: There were 13 trials involving 16,564 elderly persons (age 60 years and older). The prevalence of cardiovascular risk factors, cardiovascular disease, and competing comorbid diseases was lower among trial participants than the general population of hypertensive elderly persons. When the six large high-quality trials were combined, trial results showed 43 subjects (95% confidence interval [CI], 31 to 69) and 61 subjects (95% CI, 39 to 141) needed to be treated for 5 years to prevent one cerebrovascular event and one coronary heart disease event, respectively. Including the other seven trials did not change the results significantly. Only 18 subjects (95% CI, 14 to 25) needed to be treated to prevent one cardiovascular event (cerebrovascular or cardiac). Twelve trials in primarily younger and middle-aged adults involved approximately 33,000 persons. For all outcomes except cardiac mortality, two to four times as many of the younger subjects as the older subjects needed to be treated for 5 years to prevent morbid and mortal events. No significant effect on cardiac mortality was seen among younger subjects, while 78 older subjects (95% CI, 50 to 180) needed to be treated to prevent a fatal cardiac event. CONCLUSIONS: Randomized trials demonstrate that treating healthy older persons with hypertension is highly efficacious. Five-year morbidity and mortality benefits derived from trials are greater for older than younger subjects. Extrapolating benefits from trials to individual patients is difficult, but should take into account multiple issues including the patient's risk factors, preexisting cardiovascular disease, and competing comorbid illnesses. PMID- 7990248 TI - NIH Consensus conference. Optimal calcium intake. NIH Consensus Development Panel on Optimal Calcium Intake. PMID- 7990249 TI - Compensating physicians for telephone calls. PMID- 7990250 TI - The cost-quality relationship. Do we always get what we pay for? PMID- 7990251 TI - [Recent advances in macrolide antibiotics: focused on clarithromycin. Discussion]. PMID- 7990252 TI - [Reevaluation of current antimicrobials. Series 13: cefamandole sodium. Discussion]. PMID- 7990253 TI - [Reevaluation of current antimicrobials. Series 14: sulbactam sodium/cefoperazone sodium. Discussion]. PMID- 7990254 TI - [Reevaluation of current antimicrobials. Series 15: aztreonam. Discussion]. PMID- 7990255 TI - [Imipenem/cilastatin sodium alone or combined with amikacin sulfate in respiratory infections]. AB - In the present study, we used the envelope method to divide patients with respiratory infections into two groups: a monotherapy group given imipenem/cilastatin sodium (IPM/CS) and a combination therapy group given imipenem/cilastatin sodium plus amikacin sulfate (AMK). We then compared the clinical efficacy and safety between groups. 1. Safety was evaluated in 83 patients in the IPM/CS group and 88 in the IPM/CS + AMK group while clinical efficacy was evaluated in 77 and 80 patients in the respective groups. 2. The overall efficacy rate was 84.4% in the IPM/CS group. Among the main infections, the efficacy rates were 82.7% in 52 cases of pneumonia (including lung abscess), 100% in cases of infected bronchiectasis, 66.7% in six cases of secondary infection of chronic respiratory disease, and 100% in four cases of chronic bronchitis. The overall efficacy rate was 83.8% in the IPM/CS + AMK group. Among the main infections, the efficacy rates were 88.1% in 59 cases of pneumonia (including lung abscess), 83.3% in 12 cases of infected bronchiectasis, and 60.0% in five cases of secondary infection of chronic respiratory disease. No significant differences in efficacies were seen between groups. 3. In the IPM/CS group, the efficacy rates were 92.3% for patients without prior antibiotic therapy in the IPM/CS group and 68.0% for those with prior therapy; in the IPM/CS + AMK group, the respective rates were 83.7% and 83.9%. In the IPM/CS group, there was a significant difference in the responses of patients with and without prior antibiotic therapy (P < 0.05). 4. Side effects were observed in six patients in the IPM/CS group (7.2%) and two patients in the IPM/CS + AMK group (2.3%). Abnormal laboratory test results were noted in 5 patients in the IPM/CS group (6.0%) and in 10 in the IPM/CS + f1p4group (11.4%). There was no significant difference in the incidence of side effects between groups and no severe adverse reactions in either group. These results indicate that IPM/CS alone produces of good response in moderate to severe respiratory infections while IPM/CS combined with AMK is useful in intractable respiratory infections. PMID- 7990256 TI - [A clinical study on fluconazole against pulmonary mycosis associated with respiratory diseases]. AB - In 34 hospitals in Kyushu area, the clinical effects and safety of fluconazole (FLCZ) against pulmonary mycosis were studied. To a total of 108 patients with respiratory diseases was FLCZ administered. The results were as follows. 1. Sixty six cases were evaluable for the clinical efficacy of FLCZ. In 8 cases of pulmonary cryptococcosis, the clinical efficacy rate was 100% (8/8). In 58 cases of pulmonary aspergillosis, it was 43.1% (25/38). Overall, the clinical efficacy rate was 50% (33/66). 2. Fungi were eliminated in 3 of 6 cases in which Cryptococcus was detected, and were eliminated in 8 and reduced in 4 of 30 cases in which Aspergillus spp. including A. fumigatus were detected. 3. Side effects were observed in 5 of 87 cases (5.7%), none of them was serious, however. Abnormal results of laboratory tests that might be related to the FLCZ administration were observed in 5 cases (5.7%). 4. From these results, fluconazole appears to be a potent antifungal agent for treatment of pulmonary mycosis. PMID- 7990257 TI - [Antimicrobial activities of ciprofloxacin against recently obtained clinical isolates]. AB - In order to evaluate antimicrobial activity of ciprofloxacin (CPFX), minimum inhibitory concentrations (MICs) of CPFX and other drugs were determined against clinical isolates that were obtained in our laboratory from January to December of 1991, and of 1993. The results are summarized as follows: 1. CPFX-resistant strains were on the increase in various strains, compared to those in the early 1980s. However, many of CPFX-resistant strains were multi-drug resistant including beta-lactams. In addition, they showed cross resistance to other fluoroquinolone agents. 2. MIC distribution of other drugs suggested that there were increased frequencies of benzylpenicillin (PCG)-insensitive Streptococcus pneumoniae (PISP) and CEPs-resistant Escherichia coli. However, MIC distribution of CPFX to these resistant strains were in a relatively low range. 3. When isolates of 1991 were compared to those of 1993, we confirmed that CPFX-resistant strains decreased among certain bacteria such as Staphylococcus aureus. Also we confirmed that fewer CPFX-resistant strains were found among bacteria that may be highly related to infections encountered in daily medical care. PMID- 7990258 TI - [Antimicrobial activities of fosfomycin against Streptococcus pneumoniae and Haemophilus influenzae recently observed in sinusitis patient]. AB - In order to examine antimicrobial activities of fosfomycin (FOM), the minimum inhibitory concentrations (MICs) of FOM and those of control drugs were determined against Streptococcus pneumoniae and Haemophilus influenzae isolated from sinusitis patients from September to November, 1993, and the following results were obtained. 1. Among 50 S. pneumoniae strains tested, there were 10 strains (20.0%) of benzylpenicillin (PCG)-insensitive S. pneumoniae (PISP) and 2 strains (4.0%) of PCG-resistant S. pneumoniae (PRSP); but the MIC distributions of FOM among the PISPs and the PRSPs were almost identical to those among the PCG susceptible S. pneumoniae (PSSP). 2. There were 12 strains (24.0%) of beta lactamase producing strains among 50 strains of H. influenzae tested, but the FOM's MIC distribution among these strains was almost identical to that among beta-lactamase non-producing strains. 3. The results obtained on the MIC90s of FOM against S. pneumoniae and H. influenzae suggest that the nebulization treatment with FOM nasal preparation satisfies the condition "above the MIC". PMID- 7990259 TI - [Therapeutic efficacy of lanoconazole ointment in guinea pig model of tinea pedis, in comparison with that of cream preparations]. AB - The therapeutic efficacy of ointment and cream preparations of lanoconazole in a guinea pig model of tinea pedis was compared. When infected animals were treated once daily with 0.25% and 0.5% lanoconazole ointments, 7 of 10 and 8 of 10 infected feet became culture-negative, respectively. In animals treated with 1% lanoconazole ointment, fungus was not recovered from any infected foot. Comparing these results with those of culture study in animals which were treated with comparable concentrations of lanoconazole cream, no significant differences were found. These studies, therefore, suggested that ointment and cream preparations of lanoconazole on topical application in the tinea pedis model would show basically equivalent therapeutic efficacy. PMID- 7990260 TI - [Clinical evaluation of sulbactam/cefoperazone for infections during the chemotherapy of hematologic malignancy]. AB - In 28 patients with hematologic malignancy, the clinical effect and the safety of sulbactam/cefoperazone (SBT/CPZ) were studied on 45 episodes during granulocytopenic stage after antineoplastic chemotherapy. The overall efficacy rate obtained with SBT/CPZ in combination with other drugs was 62%. The rates for sepsis, suspected sepsis and pneumonia were 67%, 94% and 38%, respectively. The efficacy in those cases that showed granulocyte count less than 300/microliters during the course of administration of SBT/CPZ was 53%, and in those cases that showed granulocyte counts recovery to more than 300/microliters was 73%. Prior antimicrobiological treatments had no influence on the efficacy of SBT/CPZ. SBT/CPZ showed an activity spectrum covering frequently isolated microorganism including Acinetobacter calcoaceticus, Pseudomonas aeruginosa, Enterobacter cloacae and Staphylococcus aureus. Mild adverse effect were observed in 4 episodes (8.8%). These result suggested that SBT/CPZ was thought to be a useful drug for empirical therapy in granulocytopenic patients with hematologic malignancies. PMID- 7990261 TI - [The clinical study of cefpodoxime proxetil dry syrup preparation in the pediatric field]. AB - The clinical efficacy was examined for the newly developed oral cephem antibiotic, cefpodoxime proxetil (CPDX-PR) dry syrup, in the treatment of various acute infections in the field of pediatrics. CPDX-PR dry syrup was administered at 10 mg/kg/day in 3-divided doses to 535 children at 21 institutions, including Tottori University Hospital and its related hospitals. The efficacy rate of this drug was determined to be 80.8%. Among isolates, Staphylococcus aureus and Streptococcus sp. were highly susceptible to the drug, whereas Haemophilus influenzae showed relatively poor susceptibility. Side effects were observed in 2.80% of all of the patients, and abnormal laboratory findings were detected in 1.87%. The low incident of side effects demonstrated its high safety, and this drug was considered to be very useful for such pediatric infections as acute tonsillitis, acute pharyngitis and acute bronchitis. PMID- 7990262 TI - [A clinical study on the efficacy of ceftazidime and aspoxicillin in chorioamnionitis. Abdominal Infections Research Group]. AB - Chorioamnionitis as a complication of threatened abortion and preterm labor and preterm PROM were treated with ceftazidime (CAZ) and aspoxicillin (ASPC) as a primary therapy. The following results were obtained. 1. Cases of threatened abortion and preterm labor (n = 25) and preterm PROM (n = 5) were treated with 2 4 g CAZ/day alone (n = 14) or in combination with 4 g ASPC/day (n = 16) along with a uterine contraction inhibitor (ritodrine hydrochloride etc. n = 28) and clinical evaluation was made. 2. In the cases of threatened abortion and preterm labor the efficacy ratio was 24/25 (96%). In the cases of preterm PROM, the latent period-delaying effect was observed in five out of the five patients. Upon analysis of the tocolysis index in the group of threatened abortion and preterm labor, the index values > or = 5 were observed in 12 out of 25 (60%), and the delivery incidence before the 35th week of gestation was 4/25 (16%). In all patients, the incidence of delivery after the 36th week of gestation was 24/30 (80%). 3. Bacteriological examinations showed a high detection rate for Gram positive bacteria, and the combination effect between ASPC and CAZ was demonstrated against all 9 isolates examined. The above results indicated a high efficacy as well as safety of the combination of CAZ and ASPC as a primary therapeutic means against chorioamnionitis. PMID- 7990263 TI - [A clinicobacteriologic study on sultamicillin fine granules in pediatric sinusitis]. AB - We carried out clinical and bacteriological studies on sultamicillin (SBTPC) in pediatric sinusitis at 10 general practice settings. The results are summarized as follows. 1. The major isolated organisms from purulent nasal discharges were Streptococcus pneumoniae 27.5%, Haemophilus influenzae 32.4% and Moraxella catarrhalis 9.9%. Similar results were observed for the major isolates from nasopharynx. 2. 33% of the isolated S. pneumoniae were penicillin-insensitive S. pneumoniae (PISP) against which the MICs were equal to or higher than 0.1 microgram/ml. 3. PISP was isolated from 14% of all cases. 4. The clinical efficacy rate was 77.5% and was deemed satisfactory. 5. In the bacteriological study, persistence rate of PISP was 38.5% among the PISP from purulent nasal discharge and 60.0% among the PISP from nasopharynx which and these values were significantly higher than persistence rates of PSSP, H. influenzae and M. catarrhalis. 6. Adverse reactions were observed in 21.5% of all cases, involving diarrhea and loose stool. PMID- 7990265 TI - [36th annual meeting of the Japanese Society for Gastroenterology. Sendai City October 31-November 2, 1994. Abstracts]. PMID- 7990264 TI - [Clinical studies on flomoxef in acute tonsillitis]. AB - To objectively evaluate the clinical efficacy and safety in acute tonsillitis, flomoxef (FMOX) was examined for the distribution of sensitivity of clinical strains to it and for its clinical usefulness. 1. The 80% minimum inhibitory concentration of 11 clinical strains of Gram-positive bacteria, 6 of Gram negative bacteria and 5 of anaerobic bacteria was 0.39 microgram/ml. FMOX showed the strongest, most comprehensive antibacterial action among the drugs tested. 2. Thirty patients received FMOX. Clinical effectiveness was evaluated in 28 patients, and clinical usefulness and safety in 30. 3. The clinical efficacy rate ('excellent' and 'good') was 75% (21/28). 4. As for bacteriological response, bacterial elimination rates were 67% for Gram-positive bacteria, 100% for Gram negative bacteria, 100% for anaerobic bacteria and 100% for mixed infections. 5. Side effects occurred in 2 (6%) patients: drug eruption and diarrhea in 1 patient each. These symptoms improved rapidly after discontinuation of the drug. 6. Although abnormal clinical test results were found in 7 (23%) patients, i.e., increases in GOT and GPT in 2, in GPT in 4 and in BUN in 1, they were transient. 7. The usefulness of FMOX was assessed in light of its efficacy and safety. It was highly satisfactory in 14 patients, satisfactory in 11, relatively satisfactory in 1, unsatisfactory in 2 and highly unsatisfactory in 2, and rate of usefulness was 83%. FMOX is considered to be highly useful for the treatment of severe acute tonsillitis. PMID- 7990266 TI - A useful method for differential evaluation of anti-inflammatory effects due to cyclooxygenase and 5-lipoxygenase inhibitions in mice. AB - This study was performed to establish a useful method for monitoring the effects of inhibitors of 5-lipoxygenase (5-LO) and/or cyclooxygenase (CO) and for differential evaluation of these inhibitors. After oral dosing, CO inhibitors such as indomethacin (20-40 mg/kg) and ketoprofen (40-80 mg/kg), zileuton (5-LO inhibitor, 20-80 mg/kg) and MK886 (5-LO-activating-protein inhibitor, 640 mg/kg) potently suppressed arachidonic acid (AA, 0.25 mg)-induced ear edema in mice. Methysergide (serotonin antagonist, 20 mg/kg) showed a slight anti-edematous effect, while mepyramine (160 mg/kg) and bromelain (320 mg/kg) had no effect. The anti-edematous effects of indomethacin and ketoprofen were reduced by concomitant topical application of prostaglandin E2 (PGE2, 1 micrograms/ear), but not by concomitant intradermal application of leukotriene C4 (LTC4, 0.1 micrograms/ear). On the contrary, the anti-edematous effects of zileuton and MK886 were reduced by LTC4, but not by PGE2. Dual (5-LO and CO) inhibitors such as phenidone (80-160 mg/kg) and BW755C (40-80 mg/kg), which inhibited the biosynthesis of LTB4 13-15 times more potently than that of PGE2 in rat peritoneal exudate cells, also showed anti-edematous effects that were reduced by LTC4, but not by PGE2. These results suggest that the AA (0.25 mg)-induced ear edema in mice is mainly mediated by LTs and PGs and is suitable for evaluating inhibitors of 5-LO and/or CO, and that an application of LTC4 or PGE2 with AA is a useful method for differential evaluation of these inhibitors. PMID- 7990267 TI - Effects of KW-5805, a new antiulcer agent, on experimental gastric and duodenal ulcers, gastric mucosal lesions by necrotizing agents and gastric acid secretion. AB - Effects of KW-5805, a new antiulcer agent, on various experimental ulcers, necrotizing agent-induced gastric lesions and gastric acid secretion in rats were compared with those of pirenzepine and cimetidine. KW-5805 showed antiulcer activities against experimental gastric and duodenal ulcers (ED50 = 1.2-10.0 mg/kg, p.o.). KW-5805 effectively inhibited gastric lesions induced by various necrotizing agents (ED50 = 4.5-39.8 mg/kg, p.o.). In addition, the cytoprotective effect of KW-5805 was not affected by indomethacin, but reserved by N ethylmaleimide. These antiulcer and cytoprotective effects of KW-5805 were more potent than those of pirenzepine and cimetidine. In pylorus-ligated rats, intraduodenal KW-5805 administration at 30 mg/kg showed a weak antisecretory effect, which was 3-10 times less potent than those of pirenzepine and cimetidine. In rats with acute gastric fistula, intravenous injection of KW-5805 reduced methacholine-stimulated gastric acid secretion at doses of 10 and 30 mg/kg and inhibited tetragastrin-induced acid secretion at 30 mg/kg. These results indicate that KW-5805 has potent and broad antiulcer properties, which are probably exerted by its potent cytoprotective effect in addition to its antisecretory effect. PMID- 7990268 TI - Involvement of pain associated anxiety in the development of morphine tolerance in formalin treated mice. AB - The mechanism underlying the previous findings that the development of antinociceptive tolerance to morphine was significantly delayed in the presence of inflammatory pain induced by formalin was examined. Measurements of the pain threshold at different time intervals have shown that pain lasts around one week in the formalin treated mice. A single dose of indomethacin (10 mg/kg) or aspirin (400 mg/kg), 30 min before formalin injection, and daily 400 mg/kg of aspirin had no effects on the pain threshold or swelling, and it also did not affect the delay of morphine tolerance development. Daily administration of diazepam, 1 mg/kg, 1 hr before morphine injection completely abolished the delay. This effect was antagonized by 2 mg/kg of flumazenil, administered 15 min before diazepam injection. These results suggest that pain-associated anxiety participates in the delay of morphine tolerance development and consequently the benzodiazepine receptor complex plays a role in the development of morphine tolerance during a painful state. PMID- 7990269 TI - Effects of NC-1300-O-3 on gastric mucus secretion and prostaglandin release in rats. AB - We investigated the effect of NC-1300-O-3 on gastric mucus secretion and prostaglandin release into the gastric lumen in rats. NC-1300-O-3 following single or repeated administration for up to 4 weeks significantly increased the hexose content in the gastric lumen at 10 to 100 mg/kg, p.o. Omeprazole and cimetidine at doses that strongly inhibited gastric acid secretion had no effect on the hexose content following single or repeated administration for 8 days. When administered repeatedly for 8 days, NC-1300-O-3, omeprazole and cimetidine significantly decreased the hexosamine content in gastric surface mucosa, but significantly increased gastric mucus secretion was observed at the same time only with NC-1300-O-3, indicating that this agent has a profile of action on gastric mucus metabolism different from those of omeprazole and cimetidine. NC 1300-O-3 at 10 and 30 mg/kg, p.o. and omeprazole at 30 mg/kg, p.o. increased the release of prostaglandins into the gastric lumen, and this was markedly inhibited by pretreatment with indomethacin, suggesting that these agents may enhance prostaglandin biosynthesis in the gastric mucosa. From these results, it seems that the enhancement of NC-1300-O-3 on gastric mucus secretion and prostaglandin biosynthesis in the gastric mucosa contribute to the antiulcer effect of NC-1300 O-3. PMID- 7990270 TI - Histamine receptors mediating a positive inotropic effect in guinea pig and rabbit ventricular myocardium: distribution of the receptors and their possible intracellular coupling processes. AB - The difference in histamine receptor subtypes that are involved in the positive inotropic effect of histamine in guinea pig and rabbit ventricular myocardium was analytically characterized. In guinea pig papillary muscles, the positive inotropic effect of histamine was antagonized by cimetidine but not by mepyramine. The converse was true in rabbit papillary muscles. However, histamine evoked a positive inotropic effect through H1- and H2-receptors after blockade of H2- and H1-receptors in guinea pig and rabbit papillary muscles, respectively. Adenylate cyclase was significantly activated by histamine via H2-receptors in guinea pig but not in rabbit myocardial ventricular membranes. Accumulation of [3H]inositol monophosphate in ventricular strips prelabeled with myo-[3H]inositol was increased by histamine via H1-receptors to a similar extent in rabbits and guinea pigs. Radioligand binding experiments with [3H]mepyramine and [3H]tiotidine showed an increased number of H1-receptors and a decreased number of H2-receptors in guinea pig compared with rabbit ventricular myocardium. These results suggest that the positive inotropic effects of histamine are dominated by an H1-receptor-mediated effect in rabbits and by an H2-receptor-mediated one in guinea pig ventricular myocardium, and the positive inotropic effect manifested by one subtype apparently restricts the expression of the positive inotropic effect mediated by the other subtype. This species difference is not due to a difference in densities of the receptor subtypes, but may be partly related to a difference in the extents of coupling of H2-receptors to adenylate cyclase. PMID- 7990271 TI - Tacrine increases stimulation-evoked acetylcholine release from rat hippocampal slices. AB - We examined the effects of tacrine (9-amino-1,2,3,4-tetrahydroacridine) on endogenous acetylcholine (ACh) release from rat hippocampal slices. Tacrine (more than 1 microM) increased the measurable amount of basal ACh release. On the other hand, in the presence of physostigmine (50 microM; under this condition, cholinesterase activity was inhibited), tacrine did not enhance the basal ACh release. Tacrine at more than 100 microM increased the submaximal electrical stimulation-evoked release of ACh in both the absence and presence of physostigmine (50 microM). This effect of tacrine was abolished by a combination of atropine (100 mM) and physostigmine. These results indicate that a high-dose of tacrine increases cholinergic neurotransmission not only by inhibition of cholinesterase but also by increasing ACh release through an atropine-like effect, perhaps by blockade of part of the process of muscarinic autoinhibition. PMID- 7990272 TI - Effects of KCA-098 on bone metabolism: comparison with those of ipriflavone. AB - We previously found that 3,9-bis(N,N-dimethylcarbamoyloxy)-5H- benzofuro[3,2 c]quinoline-6-one (KCA-098) inhibited bone resorption in organ culture. In this study, to determine if KCA-098 is therapeutically applicable for the treatment of osteoporosis, we compared the effect of KCA-098 on bone tissues with that of ipriflavone, a drug that is clinically used for the treatment of osteoporosis. Both KCA-098 and ipriflavone inhibited parathyroid hormone-, prostaglandin E2-, 1 alpha,25-dihydroxyvitamin D3- and interleukin 1 beta-induced bone resorption of fetal rat bones, but the inhibitory activity of KCA-098 was more potent than that of ipriflavone. In fact, the effective concentrations of KCA-098 were 10 to 100 times lower than those of ipriflavone. Oral administration of KCA-098 (1 and 3 mg/kg) or ipriflavone (100 mg/kg) to ovariectomized rats on a low-calcium diet increased the breaking force and bone density of the femora, indicating that KCA 098 is an effective on the whole animal as ipriflavone. Furthermore, KCA-098 increased the length and calcium content of 9-day chick embryonic femora cultured in vitro, whereas ipriflavone did not, suggesting that KCA-098 had a direct stimulatory effect on bone mineralization. Therefore, KCA-098 seems to be more potent than ipriflavone in stimulating bone tissue formation and may thus be expected to become a useful agent for the treatment of osteoporosis. PMID- 7990274 TI - Elevated tyrosine hydroxylase mRNA levels in the adrenal medulla of spontaneously hypertensive rats. AB - We investigated the expression of tyrosine hydroxylase (TH) mRNA and its activity in the adrenal medulla of spontaneously hypertensive rats (SHR) and Wistar Kyoto rats (WKY). The TH mRNA levels were determined by Northern blot and dot blot analyses. The TH activity and the expression of TH mRNA in the adrenal medulla of SHR were significantly higher than those of WKY (P < 0.01). These results suggested that the hypertension of SHR may be related to the high activity of TH due to the high level of TH mRNA, which increases epinephrine and norepinephrine levels in the adrenal medulla. PMID- 7990273 TI - Susceptibility to adenosine agonists of giant migrating contraction induced by glycerol enema in anesthetized rats. AB - The present study examined whether adenosine agonists influence the occurrence of giant migrating contractions (GMCs) induced by glycerol enema (65%, 2 ml/kg) in rats. Catheter pressure transducers were used to measure the colonic luminal manometric alterations. The adenosine A1 agonists (2S)-N6-(2-endo norbornyl)adenosine ((S)-ENBA) (10 micrograms/kg, i.v.) and N6 cyclohexyladenosine (30 micrograms/kg, i.v.) abolished the GMCs, whereas the adenosine A2 agonist 2-[p-(2-carboxyethyl)phenethylamino]-5'-N ethylcarboxamidoadenosin e (CGS 21680) (30-300 micrograms/kg, i.v.) failed to influence the GMCs. The suppressive action of (S)-ENBA on the GMCs was entirely counteracted by the peripheral adenosine antagonist 8-(p-sulfophenyl)theophylline (10 mg/kg, i.v.). The present observations suggest that the adenosine A1 agonist suppresses the GMCs via peripheral adenosine receptors. PMID- 7990276 TI - [Significance of surgical treatment for bone metastasis from lung cancer]. AB - To assess significance of surgical therapy for patients who had metastatic bone tumor from primary lung cancer, sites of recurrence in patients who underwent surgical resection for lung cancer lesions were analyzed. Clinical courses of patients who underwent surgical therapy for metastatic bone tumor were analyzed, too. 1) From 1985 to 1989, 88 patients died from lung cancer in our hospital who has underwent pulmonary resection for lung cancer lesions. Of these, 22 patients had metastatic bone tumor. Sixty patients died who had underwent complete resection for lung cancer lesions. In eight patients of these 60 cases, bone were first site of recurrence. Of these eight patients, length from pulmonary resection to detection of bone metastasis were 4-23 months. In the other hand, length from detection of bone metastasis of death were 3-24 months. There was no correlation between two length. All of these eight patients had another metastatic lesions at the time of death. 2) From 1985 to July 1993, twelve patients underwent surgical therapy for their bone metastasis of primary lung cancer. Of these, four had metastatic cancer in thoracic vertebral body, two had in clavicle, two had in rib, three had in femoral bone, another had in tibial bone. Objective of operation were improvement of paralysis or pain, prevention of fracture, and so on. Most cases succeeded to get improvement in a short time, but some cases got worse soon. Surgical treatment was effective to improve paralysis or pain, and to increase quality of life. But it can not be effective except appropriate management in a short time because another symptom raise soon. PMID- 7990275 TI - Effects of flavonoid compounds on the activity of NADPH diaphorase prepared from the mouse brain. AB - The effects of flavonoids on NADPH diaphorase activity were studied in vitro, and we found that the enzyme activity was markedly inhibited by quercetin. This inhibitory action was shown to be accompanied by an increase in the apparent Km value of the enzyme for the cofactor NADPH, with a decrease in the Vmax, and an increase in the apparent Km for the substrate nitro blue tetrazolium, without any significant change in the Vmax. These results indicate that quercetin may directly inhibit NADPH diaphorase, thus suggesting the possibility that this compound may be able to inhibit the production of nitric oxide in the brain. PMID- 7990278 TI - [An experience of successful valve repair for acquired mitral and tricuspid regurgitation in dextrocardia, situs inversus, bilateral vena cava, and hemiazygos continuation]. AB - A 56-year-old woman was admitted to our department because of congestive heart failure. Chest X-ray showed dextrocardia with situs inversus. The echocardiography revealed severe mitral regurgitation due to prolapse of posterior leaflet and secondary Venography demonstrated the bilateral superior vena cava, huge coronary sinus and hemiazygos continuation with hypoplastic inferior vena cava. Mitral valve regurgitation was repaired by Carpentier's and Burr's technique, and tricuspid valve regurgitation was repaired by Kay's technique. Her postoperative course was uneventful. Valve surgery for acquired valvular lesion in dextrocardia with situs inversus is rare. Although valve repair is easily performed even in mirror-image heart as well as in normal, levo position heart, preoperative evaluation of systemic venous return is important in the case of dextrocardia with systemic venous anomalies. PMID- 7990277 TI - [A case of pulmonary hypertensive crisis (PHC) treated with prostaglandin E1 and tolazolin after surgery of ventricular septal defect in an adult]. AB - A 32-year-old woman was diagnosed with ventricular septal defect (VSD) with severe pulmonary hypertension (PH). Though Pp/Ps was 0.98, an operation was carried out because the index of pulmonary vascular disease (IPVD) was 1.73. Pp/Ps on the operation day was 0.51 and extubation was carried out on the next day. Five days after the operation, she suffered shock, convulsions and loss of consciousness, but these were relieved by endotracheal intubation. On the 7th day, because Pp/Ps was 0.97, we confirmed the diagnosis of PHC. PHC was treated by intravenous continuous infusion of a high dose of PGE1 (220 ng/kg/min) and tolazolin (Tz) (7-18 micrograms/kg/min) in combination with norepinephrine (0.07 microgram/kg/min) via a catheter in the descending aorta. Pp/Ps soon decreased and was 0.60 at 15 hours after administration of PGE1 and Tz. To prevent recurrent PHC, she was administered with PGE1 (20-60 ng/kg/min) intravenously for 3 weeks after improvement of PHC. As side effects of PGE1, she showed swelling and arthralgia of the hands and feet after 2 weeks. Those side effects improved after discontinuing of administration of PGE1. PMID- 7990279 TI - [Mitral and aortic valve replacement associated with aortitis syndrome: a case report]. AB - A case of aortic and mitral regurgitation associated with aortitis syndrome was presented. The patient was a 36-year-old female who admitted for palpitation and dyspnea. Left ventriculography showed moderate MR. Aortography showed moderate AR and multiple occlusive lesion of the aortic arch branches. After the inflammation was controlled, aortic and mitral valve replacement was performed. Postoperative course was uneventful. Histologically, aortic and mitral valve showed capillary increase and infiltration of inflammatory cells, mainly lymphocytes. PMID- 7990280 TI - [A resected case of sporadic myxoma of the right ventricle: the diagnosis was supported with DNA flow cytometry]. AB - We report a rare case of a 16-year-old male who had myxoma originating from septal band of the right ventricle. His ECG anomaly was found incidentally upon a physical examination. Subsequently, echocardiography and angiocardiography demonstrated a tumor occupying the right ventricular outflow tract and protruding into the main pulmonary artery in systolic phase. He was operated upon using extracorporeal circulation. By right ventriculotomy the tumor was resected together with septal tissue 5 mm around the stalk, which branched into the myocardium. The defect was closed using mattress sutures with Dacron felt strips. We also analyzed the DNA content of the tumor. The DNA flow cytometry yielded a single cell population with diploid DNA content. This result showed that the tumor is sporadic form of cardiac myxoma. His postoperative course was uneventful. Thirty months after the surgery, patient has no sign of recurrence. The DNA flow cytometry is helpful for detecting clinical behavior of the cardiac myxoma, because microscopic examination can not readily distinguish sporadic myxoma from so-called complex myxoma. PMID- 7990281 TI - [A case of chronic traumatic dissecting aneurysm of the thoracic aorta]. AB - A case of chronic traumatic dissecting aneurysm was reported. A 61-year-old man was admitted to our hospital for multiple trauma caused in traffic accident. MRI, performed for evaluation of the spinal injury, revealed dissection of the thoracic descending aorta by chance, seven months after injury. Retrospectively CT, just after admission, showed bleeding around the thoracic descending aorta. Replacement of thoracic aorta was performed after 33 months from the traffic accident, for enlargement of dissecting lumen accompanied with hoarseness. The postoperative course was uneventful and the patient returned to his daily life successfully. PMID- 7990282 TI - [Left ventricular-right atrial shunt with bacterial and rheumatic endocarditis of tricuspid valve]. AB - A 14-year-old boy who was operated on for left ventricular-right atrial shunt with bacterial and rheumatic endocarditis of the tricuspid valve (TV) is reported. The patient was pointed out perimembranous ventricular septal defect (VSD) at 4-month old and had complaint of occasional high fever for a half year. The echocardiography showed a vegetation at the TV. The vegetation did not disappear despite of administration of antibiotics for 2 weeks, and pulmonary embolism occurred. Then, the patient underwent resection of the vegetation and direct closure of VSD. The left ventricular-right atrial shunt was formed by the direct communication between VSD below TV annulus and the perforation of septal leaflet of TV adhered to the ventricular septum due to bacterial and rheumatic endocarditis. Earlier operation is needed for this type of case because antibiotics is not effective for the valvular disease. PMID- 7990283 TI - [A concomitant operation of coronary artery bypass grafting and thymectomy: a case report]. AB - A 63-year-old man was successfully operated upon concomitantly for coronary artery disease and invasive thymoma. The chest roentogenogram showed a mass shadow in the anterior mediastinum, which was 6.0 x 4.0 cm in size and irregular. Coronary angiography revealed complete obstruction of the right coronary artery and 90% stenosis of the first diagonal branch (#9). Following thymectomy combined with the resection of the left phrenic nerve and the mediastinal pleura, coronary artery bypass grafting with the major saphenous vein was performed to #4 PD and #9. This is the first report of concomitant surgery for the ischemic heart disease and invasive thymoma in Japan. PMID- 7990284 TI - [A case of aortic valve replacement and aorto-coronary bypass with left lung collapse due to thoracoplasty]. AB - A 64-year-old woman was attacked cardiac and respiratory failure in 3 times within a year. Aortic regurgitation (III degrees) and left anterior descending coronary artery 90% stenosis was recognized. %VC: 33% and %FEV1.0 75% were established. Aortic valve replacement (SJM 23 nm) and coronary arterial bypass grafting (SVG) were performed with cardiopulmonary bypass. Post operative course was no trouble and patient was discharged within 60 days. PMID- 7990285 TI - [Diagnosis of mediastinal lymph node metastasis in primary lung cancer: comparing CT scan and mediastinoscopy]. AB - In 105 patients with primary lung cancer who were operated on, the rate of diagnosis of mediastinal lymph node metastasis was determined, and the results of CT scanning and mediastinoscopy were compared. The rate of accuracy of mediastinoscopy was 93.8%, considerably higher than that of CT, which was less than 85%. For the lymph nodes other than #7, which indicate contralateral metastasis, the rate of accuracy of mediastinoscopy was even better and reached 96.3%. In the 9 patients who were proved by mediastinoscopy to have contralateral lymph node metastasis, the rate of accuracy of CT was only 44%. Mediastinoscopy was very effective in the diagnosis of mediastinal lymph node metastases from primary lung cancers. PMID- 7990286 TI - [Comparative study of type of prosthesis on late results after double valve replacement]. AB - This study was performed to clear the influence of combination of prostheses on late results by comparing our patients. The patients were divided into two groups. Group I patients received a mechanical valve in the aortic position and a bioprosthesis in the mitral position (n = 25): and group II, dual mechanical valves (n = 89). The duration of follow-up ranged from 0.2 to 13.5 years, with a total of 466 patient-years. There was no difference between the two groups in terms of actuarial survival or incidence of reoperations, thromboemboli, or nonstructural dysfunction. Group I, however, had a significantly greater incidence of structural valve deterioration, anticoagulant-related hemorrhage, and all valve-related morbidity and mortality when compared with group II. In conclusion, 1. combining a mechanical valve and a bioprosthesis is disadvantageous: 2. dual mechanical valves have excellent long-term results. PMID- 7990287 TI - [Estimation of myocardial damage after cardiac surgery by myosin light chain I and troponin T]. AB - The purpose of the study was to test cardiac myosin light chain I (MLCI) and troponin T (TNT) as markers of myocardial damage after heart surgery. Forty-three patients undergoing cardiac surgery were arbitrarily divided into three groups according to the creatine kinase MB isoenzyme (CK-MB) levels and postoperative electrocardiogram (ECG) changes. Group 1: CK MB > 100 micrograms/l and Infarction pattern changes in ECG (Infarction): Group 2: CK-MB < 100 micrograms/l and no ECG changes (minimal myocardial damage). Group 3: CK-MB > 100 micrograms/l or non specific ECG changes (myocardial injury). MLCI levels showed strong correlations with TNT levels after the operation. The peak MLCI and TNT levels in group 1 were significantly higher than in group 2. The peak MLCI in group 1 was significantly higher than in group 3. TNT showed different patterns in the Infarction and Injury groups. The study showed that MLCI and TNT estimation could evaluate myocardial damage over several postoperative days. TNT estimation could identify myocardial damage earlier than MLCI, however MLCI could discriminate perioperative infarction better than TNT. PMID- 7990288 TI - [The usefulness of combined measurements of transcranial Doppler sonogram and somatosensory evoked potentials during hypothermic cardiopulmonary bypass]. AB - Serial and simultaneous measurements of the blood flow velocity of the middle cerebral artery (MCA-V) by transcranial Doppler sonography (TCD) and somatosensory evoked potentials (SEP) were performed in 7 adult patients during hypothermic cardiopulmonary bypass (CPB). CPB was instituted by alpha-stat blood gas management until the rectal temperature stabilized at 24 to 28 degrees C and gas management was converted from alpha to pH-stat by adding 4-7% of CO2 gas into the oxygenator for 10 minutes. MCA-V during hypothermic CPB by alpha-stat management was identical with normothermic prebypass MCA-V. However it significantly increased after pH-stat conversion, suggesting that CO2 reactivity was preserved even in the hypothermic situation above 24 degrees C of body temperature. Latency of all wave components of SEP and central conduction time (CCT) prolonged and wave voltages decreased as the body temperature dropped and SEP waves almost completely recovered following the temperature resumed to the prebypass temperature. There were no significant changes developed in latency and wave forms of SEP by conversion of the blood gas management from alpha-stat to pH stat. The combined technique of TCD and SEP for detecting the real time changes of cerebral blood flow and brain function is considered to be useful to minimize the brain damage during open heart surgery. PMID- 7990289 TI - [Clinical experience and early results of aortic valve replacements with Medtronic Hall 20 A]. AB - We experienced aortic valve replacement for 18 patients (4 male and 14 female, ranging from 40 to 81 years old, mean 64 years old) with small aortic annulus with new small prosthesis. Medtronic Hall 20 A (MH 20 A). The average body surface area was 1.47 m2 (range 1.28 to 1.81 m2). One patient was died of lung cancer at 3 months postoperatively. One nonstructural dysfunction and one low cardiac output syndrome was noted during operation. Sixteen survivors with MH 20 A, showed satisfactory clinical results, except for minor thromboembolism, in 2 patients. The MH 20 A had the same function as that of MH 21 A, already reported. We concluded that aortic valve replacement by Medtronic Hall 20 A prosthesis was usefull for the patient with small aortic annulus. PMID- 7990290 TI - [Reoperative coronary revascularization without cardiopulmonary bypass]. AB - We report a case of successful reoperation of coronary revascularization without cardiopulmonary bypass. The patient was a 62-year-old man, who had undergone coronary artery bypass grafting (CABG) to the LAD and CX with two saphenous vein grafts (SVG) for the left main lesion 12 years before. He required reoperation for unstable angina due to progressive ischemic heart disease and the diseased SVG. Preoperative coronary angiogram revealed total occlusion of major 3 branches and the diseased SVG to the LAD. The reoperation was performed without cardiopulmonary bypass through the repeated median sternotomy for revascularization of the LAD and RCA. The left internal thoracic artery and the gastroepiploic artery were anastomosed to the LAD and RCA under the beating heart without any hemodynamic or electrocardiographic deteriorations. The operation was uneventfully finished in 3 hr 40 min. without the use of blood products. Postoperative angiogram showed both new grafts were widely patent, and he was discharged 14 days after the operation without angina. We also performed 4 other cases of reoperative CABG without cardiopulmonary bypass, and conclude that this technique is a safe and effective alternative in a carefully selected group of patients for reoperative CABG to reduce several technical problems related to coronary reoperation. PMID- 7990291 TI - [New technique of non-conduit repair for type III transposition of the great arteries: differences from Lecompte procedure and how to do it]. AB - Lecompte reported in 1982 an innovative technique to reconstruct the pulmonary outflow tract without using prosthetic conduit in the transposition of the great arteries (TGA) with ventricular septal defect (VSD) and pulmonary stenosis (PS). In this group, however, the Lecompte procedure appears to have some difficulties translocating the pulmonary bifurcation anterior to the ascending aorta and unable to make a physiological right ventricular outflow tract preventing pulmonary valve regurgitation. A new technique now we present consists of following:(1) The main pulmonary trunk is transected subvalvularly and connected directly to the right ventriculotomy via the left side of the ascending aorta from behind and (2) intraventricular tunnel is made with prosthetic patch directing the left ventricular blood to the aorta via VSD and (3) right ventricular outflow tract is reconstructed with PTFE patch which bears a sinus formed monocusp possessing corpora Arantii. Three consecutive patients, aged 5.8, 3.7 and 2.2 years, were treated by this technique, with excellent result. Transannular systolic pressure gradients ranged 4 to 20 mmHg (mean 10 mmHg) and each monocusp was highly competent preventing pulmonary regurgitation. All the patients were able to return home within a month after the operation. We conclude that the main pulmonary trunk can be directly connected to the right ventricle by the natural route if its full extent is efficiently utilized. This technique also facilitates the insertion of competent pulmonary valve which brings good result in the postoperative cardiac performance. PMID- 7990292 TI - [Hemodynamic effects of Amrinone in patients following open heart surgery]. AB - The hemodynamic effects of amrinone, a phosphodiesterase III inhibitor, were studied early after cardiac surgery in 10 patients. CI, SVI and SWI increased significantly. SAP, mPCWP, TSVR and PVR decreased significantly. DO2 and VO2 increased significantly. HR and DP were not affected. These data demonstrate that amrinone is a valuable inotropic agent with vasodilating effect for the early post-operative management of cardiac surgical patients, since it augments left ventricular performance without increase of myocardial oxygen consumption and induction of arrhythmia. PMID- 7990293 TI - [Effect of nicardipine cardioplegia on A-V conduction system in coronary bypass surgery]. AB - The effect of diltiazem and nicardipine cardioplegia on A-V conduction system was analyzed in 75 patients undergoing coronary bypass operation. The dose of these drugs into the crystalloid cardioplegia was 10 micrograms/kg in nicardipine group (n = 29) and 100 micrograms/kg in diltiazem group (n = 46). Among these patients, there was no operative death and no patient required IABP after surgery and there was no difference on the post operative CK-MB level, on the cardiac index and on the pulmonary pressure between two groups. The number of patients who had complete A-V block after release of aortic cross clamping was significantly smaller in nicardipine group than in diltiazem group: 45.7% in diltiazem group vs. 6.9% in nicardipine group at 30 minutes and 21.7% vs. 6.9% at 60 minutes. We conclude that the suppressive effect on A-V conduction system was significantly lower in nicardipine cardioplegia than in diltiazem cardioplegia in the patients undergoing coronary bypass operation. PMID- 7990294 TI - [Radionuclides in urology]. PMID- 7990295 TI - [Combination therapy of high energy under water shock waves and anticancer drugs for subcutaneous murine bladder cancer (MBT-2)]. AB - The effect in combination therapy of high energy under water shock waves (HESW) and anticancer drugs for subcutaneous murine bladder cancer (MBT-2) in C3H/He mice was examined. HESW were generated by piezoceramics and directed to the subcutaneous tumor under ultrasonographic guidance. The subcutaneous tumor was exposed to HESW alone (100 MPa, 1000 shots, 3 shots/sec) or in combination with pirarubicin (THP, 5 mg/kg, i.p.) or carboplatin (CBDCA, 40 mg/kg, i.p.). Remarkable bleeding in the tumor was seen immediately after the exposure of HESW, destroyed cancer cells appeared after one day and wider and clearly bordered tumor necrosis was observed after three days. In the HESW alone therapy, tumor growth of smaller tumors (< 10 mm3, n = 8) were suppressed more than that of larger tumors (10-35 mm3, n = 11). Tumor growth ratio on the 14th day (TGR 14) (tumor volume on the 14th day/tumor volume on the 1st day) was examined in larger tumors. TGR 14 were 152.2 +/- 146.6 (mean +/- S.D.) in the control (n = 20), 116.3 +/- 98.9 in HESW alone (n = 11), 75.5 +/- 110.7 in THP alone (n = 8), 90.7 +/- 61.6 in CBDCA alone (n = 6), 75.8 +/- 72.2 in THP + HESW (n = 9), 3.2 +/- 4.5 in CBDCA + HESW (n = 8) and 0.8 +/- 1.3 in CBDCA + HESW 2 cycles (n = 9). Evident suppression on tumor growth was more often seen in CBDCA + HESW and CBDCA + HESW 2 cycles therapies than in the other therapies (p < 0.01). The cumulative survival rates were higher in CBDCA + HESW and CBDCA + HESW 2 cycles therapies than in the other therapies (p < 0.05). Tumor metastasis was seen only in the lungs of the dead mice after 19 days. Lung metastases were seen in 1/6 in the control, 0/5 in HESW alone, 1/5 in CBDCA alone, 0/6 in CBDCA + HESW and 1/5 in CBDCA + HESW 2 cycles therapy, respectively. PMID- 7990296 TI - [Etiological analysis of male diabetic erectile dysfunction with particular emphasis on findings of vascular and neurological examinations]. AB - We studied the nocturnal penile tumescence (NPT) value obtained by simple method and the vascular and neurological findings closely related to the ability to achieve/maintain an erection in order to investigate the causative factors of organic erectile dysfunction seen in diabetes. Studies were carried out on 62 male diabetics (32-78 y.o.). The results were as follows. 1. There were no cases of a decrease in the nocturnal penile tumescence (NPT) value among eight subjects who showed no erectile dysfunction. However, a decrease in the NPT value was recorded in 28 (85%) of 34 subjects who showed complete failure to achieve/maintain an erection. It was, therefore, surmised that there is a large organic contribution to the erectile dysfunction seen in diabetes. 2. We determined the penile blood pressure index (PBPI), the reactions of papaverine tests, conduction velocity of the dorsal nerve of the penis and the latency of the bulbocavernosus reflex. 42 (67.7%) of the 62 subjects had penile vascular disorders and the cases with severe vascular disorders were skewed to the high age brackets. There were also many cases with neuropathy involved in the ability to achieve/maintain an erection: 38 (61.2%) of the 62 subjects. Moreover, many of the subjects were found to have damage to both the blood vessels and the nerves relating to an erection, and these forms of damage were surmised to be deeply involved in the decrease in the NPT value. 3. Multivariate analysis indicated that the most important factor involved in the decrease in the NPT value was vascular damage (contribution rate: 30.8%), followed by neuropathy (6.9%). These two factors represented the most important explanatory factors of the organic erectile dysfunction seen in diabetes. 4. The contribution rate of vascular damage to the decrease in the NPT value was 18.8% for diabetic subjects under the age of 60 years, but 45.1% for subjects aged 60 years or more. The contribution rate was thus higher in the elderly subject group. On the other hand, the contribution rate of neuropathy to the decrease in the NPT value was 7.7% for diabetic subjects under the age of 60 years, but the rate decreased to 4.7% for subjects aged 60 years or more. PMID- 7990298 TI - [Study on nocturnal penile tumescence (NPT) in healthy males study on age-related changes of NPT]. AB - Nocturnal penile tumescence (NPT) occurs in all healthy males as a physiological phenomenon. Male sexual function can be evaluated by NPT. However, the age dependent changes and the significance of NPT have still remained unknown. Thus, we measured NPT throughout the night in healthy 189 subjects, ranging from 3 to 84 years old, and studied the relationship between this phenomenon and age. The parameters obtained by NPT appeared to be greater in men over about 10 years old. This increase of the parameters was related to the maturation of the hypothalamo pituitary-testicular axis, which starts rapidly at puberty. A significant decrease in the total tumescence time in men over 30 years of age was related to a decrease of androgen. In men over 55 years of age, the maximum penile circumference change and the maximum increase rate in penile circumference were significantly lower than those of men in their twenties. These results suggest that the decrease in the parameters of NPT in men over 55 years of age had a relationship with the decrease of androgen, and organic changes in the corpus cavernosum and penile vascular system that occurred with aging. In conclusion, NPT may be related to the sexual maturation and decline in men. We also provide standard reference parameters for NPT in Japanese, which could be useful in the diagnosis and treatment of male sexual dysfunction. PMID- 7990297 TI - [Urethral opening pressure as a parameter for introduction of the proper voiding modality in myelodysplastic patients]. AB - To introduce the proper voiding modality to patients with myelodysplasty, urethral opening pressure (UOP), an intravesical pressure just at the beginning urine flows out beyond the external urethral sphincter, was measured in 63 myelodysplastic patients. Among 45 renal units with any morphological or functional changes at the first UOP measurement, 37 units (82.2%) were included in the high UOP group (> or = 35 cmH2O). And among 41 ureters with VUR of more than grade 2, 32 (78.0%) were in the high UOP group. In addition, deformity of the urinary bladder was observed in 36 patients, and 26 (72.2%) of these bladders showed high UOP values. Therefore, all the patients could be divided into two groups: high UOP group (> or = 35 cmH2O, 28 cases) and low UOP group (< 35 cmH2O, 35 cases). Twenty-three patients (82.1%) with high UOP values had been mainly treated with clean intermittent catheterization (CIC). In contrast, 24 patients (68.6%) with low UOP values had been allowed to urinate by Crede' or Valsalva's method. In the followup study for 40 to 44 months, patients in the CIC group obtained good prognosis as for morphological or functional changes of the urinary tract. On the other hand, patients in the Crede' or Valsalva's method group showed a significantly higher deterioration rate in the high UOP group (80.0%) than that in the low UOP group (9.1%) (p < 0.005). From these results, hopely that in myelodysplastic patients with the underactive detrusor, CIC may be introduced for low pressure voiding to those who show high UOP values as early as possible. On the other hand, those who show low UOP values may be managed with Crede' or Valsalva's method as well as CIC. Thus, UOP is considered a possible prognostic factor for the morphological and functional changes of the urinary tract, which may be a useful parameter in decision of voiding modalities in myelodysplastic patients. PMID- 7990299 TI - [Study on nocturnal penile tumescence (NPT) in healthy males. Study on the relationship between the serum free testosterone level and NPT]. AB - We studied the correlation of nocturnal penile tumescence (NPT) and serum free testosterone, which were evaluated in 123 healthy males and in 6 cases of primary hypogonadotropic hypogonadism before and after treatment with human chorionic gonadotropin (hCG). In healthy subjects 3 to 84 years old, the serum free testosterone levels had a relationship with 4 parameters revealed by NPT: total tumescence time, mean tumescence time, maximum penile circumference change and maximum increase rate in penile circumference. In men who showed the peak value for each NPT parameter and those who were younger, the serum free testosterone levels were correlated with all 6 parameters revealed by NPT: total tumescence time, NPT frequency, mean tumescence time, circumference in flaccid penis, maximum penile circumference change and maximum increase rate in penile circumference. In 6 cases of the primary hypogonadotropic hypogonadism, total tumescence time, mean tumescence time, maximum penile circumference change, and maximum increase rate in penile circumference significantly increased after hCG treatment. This indicated that an increase of the serum free testosterone level was responsible for the increase of the parameters of NPT. In men who were older than the subjects showing the peak value for each NPT parameter, the serum free testosterone levels were correlated with 4 parameters revealed by NPT: total tumescence time, mean tumescence time, maximum penile circumference change and maximum increase rate in penile circumference. These results suggest that the free testosterone level may be involved in the decrease of maximum penile circumference change as well as in age-related changes of the penile vascular system that were the major factor responsible for the decrease. This is the first report that studied the relationship between NPT and androgen in any group. NPT as a parameter for the erectile function was related to androgen levels. PMID- 7990300 TI - [Assay of urinary pyridinoline and deoxypyridinoline as potential markers of the rate of bone resorption: usefulness of urinary pyridinoline and deoxypyridinoline in patients with prostate cancer with bone metastases]. AB - The collagen crosslinks, pyridinoline (Pyr) and deoxypyridinoline (D-Pyr), were recently identified as potential markers of the rate of bone resorption. To determine whether urinary concentrations of Pyr and D-Pyr might provide an early warning of bone metastases in patients being monitored for cancer of the prostate, we compared these two newer parameters with the conventional indicators, that is, the serum concentrations of Bone Gla protein (BGP: osteocalcin) and alkaline phosphatase (ALP), in patients with prostate cancer with and without bone metastases vs. those of age-matched patients with benign prostatic hyperplasia (BPH). Urinary excretion of these compounds, expressed as a ratio to urinary creatinine (mg/dl), was determined by high performance liquid chromatography (HPLC) in 23 patients with prostate cancer (16 with bone metastases and 7 without bone metastases) and in 23 patients with BPH. The mean values of urinary Pyr and D-Pyr; 65.02 +/- 38.16 pmol/mumol of creatinine and 8.87 +/- 7.01 pmol/mumol of creatinine and 8.87 +/- 7.01 pmol/mumol of creatinine, respectively, for patients with bone metastases of prostate cancer were significantly higher than those for patients without bone metastases of prostate cancer (27.43 +/- 10.29 pmol/mumol of creatinine and 4.24 +/- 1.88 pmol/mumol of creatinine) or for patients with BPH (25.58 +/- 7.54 pmol/mumol of creatinine and 3.52 +/- 1.07 pmol/mumol of creatinine). Among these three groups of patients, there were statistically significant (Pyr: P = 0.0001, D-Pyr: P = 0.001).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7990301 TI - [A study on predicting factors of the effect of intra-arterial infusion chemotherapy in patients with bladder cancers: the usefulness of in-vitro chemisensitivity test measuring intracellular ATP contents (ATP assay)]. AB - We studied a relationship between in vitro sensitivity of the tumors to anti cancerous drugs and histopathological effectiveness of an intra-arterial infusion chemotherapy in 15 patients with bladder cancers. The in vitro sensitivity test was performed by measuring intra-cellular ATP contents (ATP assay). The intra arterial chemotherapy were performed by injecting methotrexate (MTX), adriamycin (ADM) and eisplatin (CDDP) from the internal iliac artery. When the intra cellular ATP contents of the tumor cells treated with an anti-cancerous drug decreased to less than 50% of the untreated tumor cells, the tumor was evaluated as sensitive to the drug. The effectiveness of the chemotherapy were histopathologically evaluated by a pathologist according to the response criteria for bladder cancer treatment. When the histopathological responses of higher than grade 2 were observed in the tumor, the chemotherapy was evaluated as effective. In 8 of 9 tumors sensitive to ADM, chemotherapy were effective histopathologically and in all 6 tumors resistant to ADM, histopathological response of the chemotherapies were poor. The overall coincidence ratio between sensitivity to ADM and the histopathological effectiveness of the chemotherapy was 93%, showing statistically significant correlation. In 7 of 12 tumors sensitive to CDDP, the chemotherapies were effective and in 2 of 3 tumors resistant to CDDP, the chemotherapies were ineffective. Although the overall coincidence ratio between the sensitivities to CDDP and chemotherapeutic effectiveness was 60%, there was no significant correlation between them. In 7 of 8 tumors sensitive to both of ADM and CDDP, the chemotherapies were effective and in 6 of 7 tumors resistant to at least one of them, the chemotherapies were ineffective. (ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7990302 TI - [Biochemical analysis of the external striated urethral sphincter of male rabbits. Difference in the proportions of muscle fiber types in the male rabbit external urethral sphincter by axial subdivisional study]. AB - We studied the difference in the proportion of fast and slow myosin subunits in axially subdivided external urethral sphincter of male rabbit using myosin light chain and heavy chain analyses. The whole urethras from 6 adult male Japanese White rabbits were sagittally bisected and one halves from all animals were processed for myosin light chain analysis and another halves from all animals for myosin heavy chain analysis. Each half urethra containing the external urethral sphincter was subdivided into 4 parts, namely prostatic (P), prostatic apical (PA), infraprostatic (IP) and bullbourethral glandular (BUG) portions, from cranial to caudal direction. The electrophoretic samples from 4 different parts were separately processed. The external urethral sphincter muscle in each part from all animals were processed together for a sample because of the minute amount of the muscle. Two-dimensional electrophoresis according to the procedure of O'Farrell for myosin light chains and SDS-polyacrylamide gel electrophoresis containing 40% glycerol for myosin heavy chains were carried out. Molar ratio of myosin subunits were estimated by the dye elution procedure. The relative proportions of slow myosin molecules in respective parts were 33.4% (P), 26.3% (PA), 18.5% (IP) and 11.0% (BUG) from myosin light chain analysis and 20.3% (P), 16.1% (PA), 7.2% (IP) and 5.0% (BUG) from myosin heavy chain analysis. The urethral striated musculature in male rabbit was predominantly composed of fast myosin subunits as a whole. But the proportion of slow myosin subunits occupied a relatively high percentage in the proximal region and tended to decrease toward the distal end.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7990303 TI - [Comparison of tumor markers versus their relative values to prostatic volume in detecting prostate cancer]. AB - Diagnostic utility of serum markers and their relative values to prostatic volume were evaluated using Receiver Operator Characteristics Analysis (ROC analysis) in 173 patients who underwent ultrasound guided biopsy of the prostate gland. Seventy cases (40.5%) of prostate cancer were detected. As a whole, prostate specific antigen density (PSAD) and prostate specific antigen (PSA) were more useful than gammaseminoprotein density (GSMD), gammaseminoprotein (GSM) and prostatic acid phosphatase in diagnosing cancer judged by the area under the ROC curve denoting a test's diagnostic accuracy (p < 0.05). No significant difference was noted, however, between PSAD and PSA (p > 0.05). Prostate specific antigen density was more predictive for prostate cancer than PSA in a subgroup of patients with PSA levels of 2.0-10.0 ng/ml (p < 0.05). No advantage of PSAD was obtained in patients with intermediate PSA levels of 2.0-5.0 ng/ml or benign feeling glands (p > 0.05). Higher sensitivity could be achieved by using Eiken PSA 2.0 ng/ml as a cutoff rather than the recommended value of 3.0 ng/ml. This helped to diagnose 5 more cases of prostate cancer who otherwise might have been missed if PSA cutoff of 3.0 ng/ml had been used. A PSAD cutoff of 0.15 has a sensitivity of 81.4%, a specificity of 87.4% and an accuracy of 85.0%. However, use of this cutoff for biopsy could result in unacceptable numbers of undiagnosed cases, including many potentially curable cancers. Though PSAD may enhance sensitivity and specificity in a certain group of patients, this gain is not sufficient to reliably define the group at highest risk of prostate cancer. Indication of biopsy should still be determined based upon PSA concentration rather than PSAD value. PMID- 7990304 TI - [The prognostic value of mean nuclear area and mean nuclear volume in bladder cancer]. AB - To evaluate the prognostic value of mean nuclear area (MNA) and mean nuclear volume (MNV) in bladder cancer, a retrospective study was performed comprising 67 bladder cancer patients who could be followed up for more than 3 years. Cosmozone 1SA, a Nikon image analyzing system was used for the morphometric study. The specimen of initially biopsied tumor tissue was set in an Olympus microscope at 400-fold magnification, and the image was superimposed on the monitor picture through a video camera attached to the microscope. MNA and MNV were measured by tracing the contour of the nucleus which were selected by the point-sampled intercept methods. The time required for measurement of the area and volume was about 15 minutes per case. MNA in cases with histological grade 1, 2 and 3 were 35 +/- 3 microns2 (mean +/- SD), 42 +/- 10 microns2 and 62 +/- 12 microns2 respectively. MNV with grade 1, 2 and 3 were 282 +/- 46 microns3, 371 +/- 148 microns3 and 644 +/- 182 microns3 respectively. The morphometric results were significantly related to histological grade. In cases with a value of MNA of 40 microns2 or more and/or a value of MNV of 370 microns3 or more, the proportion of cases who underwent cystectomy or died of cancer was significantly high and demonstrated poor survival. In contrast, those who showed MNA and MNV less than the above value had better prognosis. These results suggest that the measurements of MNV seems to be useful for objectively evaluating the malignant potential of bladder cancer. PMID- 7990305 TI - [Ultrastructural consequence of shock wave exposure on VX2 cancer implanted to the urinary bladder]. AB - In order to clarify the ultrastructural consequence of the VX2 cancer cell exposed to underwater shock waves. The VX2 cancer implanted to the urinary bladder of rabbit was received the shock waves (1000 shots, 100 MPa, 5/sec.) generated by the piezo-ceramics. Damage to the cancer cell were manifested by the three kind of findings: the one was the cell junction failure which caused the isolated cells; the second was the destruction of organelle which seemed to form the vacuole in cytoplasm; and the last finding was the emergence of moth eaten appearance in the exposed cell. We conclude that underwater shock wave exposure induces lethal injury in VX2 implanted cancer. PMID- 7990306 TI - [A case of adrenal lipoma]. AB - Lipoma of the adrenal gland is extremely rare. This condition was first described in 1988 and only seven cases have been reported to date. We have experienced a case of adrenal lipoma which was thought to be adrenal myelolipoma on computed tomography (CT). A 56-year-old man was admitted to our department with a complaint of left abdominal pain. Sonography revealed a hyperechoic mass above the left kidney, and a CT scan revealed the mass to be comprised sharply marginated and an inhomogeneous structure. The tumor was comprised of areas of different density including a fatty tissue portion. These findings were strongly suggestive of adrenal myelolipoma or liposarcoma, and a left adrenalectomy was performed. Macroscopically, the tumor was consisted of yellow fatty mass and necrotic areas, which were surrounded by thin fibrous capsule. The adrenal gland was compressed at the bottom of the tumor. The weight of tumor was 290 g. Microscopically, the tumor consisted of large fat cells in direct contact with adrenal cortical cells, and it was then diagnosed adrenal lipoma. Postoperatively, the patient no longer experienced left abdominal pain and there has been no recurrence in the 31 months since the operation. PMID- 7990307 TI - [Bilateral spermatocele developed after vasectomy: a case report]. AB - A rare case of bilateral spermatocele developed 17 years after vasectomy was presented. A forty-seven year old man visited to our hospital with a chief complaint of swelling of bilateral intrascrotal contents. Sonographic findings demonstrated multilocular lesions of the bilateral intrascrotal contents. Operative procedure revealed bilateral cysts originating from the caput of the epididymis. Bilateral epididymectomy were performed. It was diagnosed as spermatocele because of demonstration of spermatozoa in the cystic fluid. We concluded that bilateral spermatocele has been induced by prolonged increased pressure of the intraepididymal duct following vasectomy 17 years ago. PMID- 7990308 TI - [Chyluria treated with inguinal lymphangiovenous and lymph node-venous anastomosis: a case report]. AB - Stripping and ligation of the renal lymphatics has been a standard operation for patients with chyluria in Japan. However, recently, inguinal lymph node-saphenous vein anastomosis and lymphangiovenous anastomosis in the spermatic cord or the lower limb are introduced as a microsurgical treatment of chyluria with good result from China. We present a case of 50-year-old female with chyluria, which was cured by the lymphatic-venous anastomosis at the groin. The patient had lived in Okinawa, an area of endemic filariasis, till 23 years of age. She noted chyluria for the first time at 28 years of age, when it was treated by irrigation of the renal pelvis with silver nitrate solution. The symptom recurred at 48 years of age, and fatigue developed two months before admission. The conservative treatments including rest, low fat diet and repeated irrigation of the renal pelvis were carried out, but these were ineffective. Therefore, bilateral inguinal lymph node-saphenous vein anastomosis and lymphangiovenous anastomosis in the same wound on the right were performed. The chyluria disappeared five months after the operation. The lymphatic-venous anastomosis at the superficial part of the body may be the surgical procedure of choice, because they are effective, simple, less invasive and less traumatic. PMID- 7990309 TI - [Results of surgical treatment of bronchiectasis in children]. AB - Among the causes of complications occurring in the early postoperative period in children is purulent endobronchitis which in most cases cannot be arrested in the preoperative period by the traditional methods of bronchoscopic cleansing. Endobronchial application of a helium--neon laser beam in a complex with the traditional methods in the preoperative period allows endobronchitis to be arrested and the postoperative complications to be reduced to 3% of cases. PMID- 7990310 TI - [Echinococcotomy of the upper lobe of the lung in children]. AB - The authors analysed the immediate and late-term results of echinococcectomy of the upper pulmonary lobe in 71 children 3 to 14 years of age conducted by Delbet's (18), A. A. Vishnevsky's (20) and A. T. Pulatov's method (25), 8 children underwent lob--and segmentectomy. Tense cysts were found in 34 and complicated cysts in 25 children. Most of the cysts (37) were localized in the anterior segment of the superior pulmonary lobe. The superior lobes of both lungs were involved with equal frequency. Deformity of the bronchi and pneumosclerosis were encountered in the late periods after Delbet's operation. Residual cavities were formed in 10 out of 20 patients after A. A. Vishnevsky's operation. In 10 patients these operations were complicated by hydro- and pneumothorax at the site of the removed cyst of the superior pulmonary lobe. These complications were due to inadequate drainage of the pleural cavity in the eighth intercostal space. Additional drainage had to be installed in the second intercostal space. The mentioned operations are indicated only in superficial localization of hydatid cysts of small and moderate size in the superior lobe, when the depth and breadth of the residual cavity resulting from echinococcectomy will be no more than 5-6 cm. Creation of an artificial interlobar or intersegmental fissure proved to be the most optimal and effective method of echinococcectomy in large cysts and centrally situated cysts of any size in the upper pulmonary lobe. Fatal outcomes were not encountered. PMID- 7990311 TI - [Outcome of surgical treatment of thyroid gland diseases in children]. AB - The authors analyse the results of surgical treatment of 254 children with various diseases of the thyroid and follow-up periods of 12 months to 20 years. They recommend the optimal time for and the volume of the operative intervention according to the form of the goiter and the children's age. The causes of the development of postoperative hypothyroidism and a recurrence of thyroid diseases in childhood are discussed and the measures for their prevention are indicated. PMID- 7990312 TI - [Hirschsprung's disease in newborns]. AB - The authors examined and treated 52 newborn babies and infants with Hirschsprung's disease. The total form was encountered in 25%, the subtotal in 23.1%, the rectosigmoid in 36.5%, the rectal in 9.6%, and the supraanal in 5.8% of cases. The clinical picture was characterized by retention of meconium (94.2%), regurgitation or vomiting (75%), abdominal distention (100%). Irrigography with calculation of the rectosigmoid ratio was conducted in 35 children, histochemical examination in 46, and histological examination in 38 children. Twenty-four (68.5%) children had the third phase of disturbed proportion of the intestinal bacteria with clinical manifestations of enterocolitis. Emergency decompression of the intestine for low acute intestinal obstruction was carried out in 27 newborn babies. Twenty children were subjected to radical surgery in the first 2-4 months of life. The choice of the operative method was guided by the form of the disease and the length of the aganglionic zone. PMID- 7990313 TI - [Gastrointestinal motility disorders in late stages of adhesive intestinal obstruction in children]. AB - The results of examination and treatment of 211 patients with late adhesive ileus (LTAI) are discussed. Highly sensitive noninvasive method of phonoenterography was used for LTAI diagnosis and control of the efficacy of non-operative treatment. The gastrointestinal motor-evacuation disorders were studied in a group of patients with chronic recurring LTAI. For revealing hypertension in the upper parts of the gastrointestinal tract, a special catheter is suggested by means of which the pressure in the gastric and duodenal cavities can be measured simultaneously. The suggested examination methods allowed a differentiated approach to the choice of the therapeutic tactics, objective control over the efficacy of the treatment, and substantiation of the indications for planned operative treatment of patients with a recurrent course of LTAI. PMID- 7990314 TI - [Duodenal atresia]. AB - The article deals with 5-year (1986-1992) experience in the diagnosis and treatment of duodenal atresia in 26 infants. Timely diagnosis of this developmental anomaly, the variants of operative treatment, and the principles of postoperative management are discussed. The necessity of antenatal ultrasonic examination and the high diagnostic value of radiological and endoscopic methods of diagnosis are emphasized. Operations were conducted on 25 children for total high intestinal obstruction, on 23 infants in the neonatal period. The continuity of the intestinal tube was restored by duodenoduodenostomy (12), duodenojejunostomy (3), gastroduodenostomy (1), excision of the membrane (4), and dissection of the membrane (5). The latter is technically the simplest and is the operation of choice. Preliminary jejunostomy for adequate preparation for the radical operation is recommended in profoundly preterm infants with as serious premorbid background. Of high importance is postoperative enteral catheteral feeding which is begun from the first day after the operation. Seven out of the 26 patients died from severe combined developmental anomalies and infection. The mortality was 26.9%. PMID- 7990315 TI - [Restoration of continuity of the large intestine after large resections in children]. AB - The continuity of the large intestine in wide resections in children aged from 7 months to 14 years was restored by rotation of the cecal cupula and ascending part through the lateral canal on a vascular pedicle. Experience in 20 operations and different variants of colorectal anastomosis is discussed. Three children had complications in the form of stenosis of the anastomosis and necrosis of the distal part of the transposed intestine as the result of disturbed circulation. PMID- 7990316 TI - [Radical surgical correction of anorectal anomalies in children by the method of posterior sagittal anorectoplasty]. AB - In the period from 1987 to 1991, radical operations by the method of posterior sagittal anorectoplasty were conducted on 29 children with anorectal anomalies, whose ages ranged from zero to 10 years. In this group 12 patients were under the age of six months. The diagnosis was based on the presence of external clinical signs of the anomaly, ultrasonic scanning of the organs of the chest, abdomen, and true pelvis, as well as on the findings of the generally accepted radiological methods. In 23 children the radical operation was preceded by colostomy. Hyperbaric oxygenation was applied in the postoperative period in all patients. The late-term results were studied in 17 patients, they were found to be good in 12 patients and satisfactory in one patient. Mortality was not encountered in this group of patients. PMID- 7990317 TI - [Specific features of pediatric surgery]. PMID- 7990318 TI - [Prognosis in the course of postoperative period in acute appendicitis in children]. AB - To determine the informative significance of the myoglobin test for prognosticating the postoperative complications in children treated by surgery for acute appendicitis, the authors compared the content of serum myoglobin in patients with a favorable (31 children) and in those with a complicated (12 children) course of the postoperative period. The detected peculiarities of the initial (at the time of the operative intervention) myoglobin level and its changes in the first two postoperative days allowed the possibility of the development of postoperative pyoinflammatory complications to be predicted with an accuracy of up to 75%. PMID- 7990319 TI - [Immunotherapy for the treatment of acute appendicitis in children]. AB - The immune status was studied during the development of the disease in 182 children who were operated on for acute appendicitis. T lymphocytes and their subpopulations circulating in the blood, as well as B lymphocytes, immunoglobulins A, M, G, and immune complexes were determined. The character of changes of these values before the operation and in various postoperative periods were determined. The effect of complex treatment, including T-activin, on the clinical and immunological parameters in children with acute appendicitis was appraised. Analysis of the results showed that a transitory immunodepressive state forms in children with the disease, which is more marked in the destructive form, with normalization of the main values of cell-mediated and humoral immunity by the 7th day after appendectomy. In a complicated course of acute appendicitis the state of immunodeficiency is torpid in character and does not return to normal values even after clinical recovery, i.e. before discharge from the clinic. Inclusion of the immunostimulating agent T-activin into the complex treatment of patients with appendicitis ensures a more rapid involution of the main clinical manifestations of the disease. The therapeutic effect was most pronounced in destructive appendicitis: after 3 days of treatment the pain syndrome was encountered twice less frequently and intestinal paresis more than twice less frequently in these patients, and the term of hospital stay (8.8 +/- 0.4 days) was less shorter than for children of the control group (12.2 +/- 1.9 days) who did not receive T-activin in the therapeutic complex. PMID- 7990320 TI - [Surgical treatment of extrahepatic portal hypertension in children]. AB - In the period from 1985 to 1992 sixty-three patients aged from 7 months to 15 years were treated for the portal hypertension syndrome, 60 had the extrahepatie form. Forty-five various operations for portosystemic shunting were carried out: formation of proximal splenorenal anastomosis in 31, distal splenorenal anastomosis in 4, mesentericocaval anastomosis in 6, gastrocaval anastomisis in 2, and an atypical vascular shunt in 2 cases. Nonshunting operations were performed on 8 patients. Since 1986 39 sessions of endoscopic sclerotherapy were conducted, 16 of them were carried out in cases with esophagogastric bleeding. PMID- 7990321 TI - [Congenital and acquired deformities of knee joint menisci in children]. AB - Children with congenital and acquired pathology of the menisci account for 7.2% of all patients with internal pathological conditions of the knee joint. The clinical manifestations are due to instability of the joint. In rupture of normally developed menisci the instability is acute or subacute and is displayed by general unspecific reactive symptomatology. The clinical signs of instability are revealed in children with anomalous development of the menisci due to decompensation of the defence-adaptational mechanisms and are evidence of a chronic pathological condition. A precise topical diagnosis of pathology of the menisci may be established only by means of special examination methods among which arthropneumography plays the principal role. The studies made it possible to distinguish and describe a previously unknown pathological condition--abnormal attachment of the menisci to the transverse ligament of the knee. Paracapsular resection of the ruptured or discoid meniscus through a wide parapatellar approach is the optimal surgical policy. Rational postoperative management consisting in early and prolonged kinesitherapy with exclusion of an axial load on the limb and a system of active medical follow-up restore the stability of the knee joint and its full function in 95% of patients and maintain it for postoperative periods of up to 10 years. PMID- 7990322 TI - [Cryosurgery in the treatment of suppurative diseases of the soft tissues in children]. AB - The method of cryosurgical debridement in purulent diseases of the soft tissues in children is simple, effective, shortens the time for treatment by 23.4%, and has practically no contraindications. Cryosurgical debridement of the purulent focus accelerates rejection of the necrotic tissues, increases the flow of blood in the region of the wound, and stimulates the regeneration processes. The cryogenic effect reduces the resistance of the microflora to antibiotics without causing an essential influence on the content of microbes in the wound, and also has a favorable effect on the functional activity of the cells of the inflammation. PMID- 7990323 TI - [Laser and ultrasonic therapy in the treatment of acute purulent diseases of the soft tissues in children]. AB - The article analyses the results of active treatment of pyoinflammatory diseases in 138 children by means of CO2-laser and ultrasonic cavitation. The control group was formed of 145 children who were treated by the commonly applied methods. The efficacy of surgical debridement was appraised according to the number of bacteria per g of tissues. Various methods of opening and treatment of the purulent cavity are compared. The differentiated use of the laser beam and ultrasonic cavitation depending on the character of the pathological process is substantiated. The schemes of ultrasonic cavitation with the use of various solutions and their combination depending on the phase of the wound process are shown. A combination of laser cleansing and ultrasonic cavitation is most rational. Complete epithelialization of the wound occurs 5-6 days earlier than in the control group. PMID- 7990324 TI - [Treatment of diabetic foot gangrene]. PMID- 7990325 TI - [Prevention of postoperative complications in diffuse purulent peritonitis in children]. AB - A complex pathogenetic approach to the prevention of postoperative complications in generalized fibrinopyogenic peritonitis is suggested. It includes a wide operative access, one-stage cleansing with antiseptics and detoxification solutions, ultrasonic cavitation of the abdominal cavity, creation of laparostomy, local infiltration of the wound edges with 0.01% thymalin solution, correction of hemostasis disorders, and increase of the organism's general reactivity. With the use of this complex the results of treatment were significantly improved in 21 children and the number of complications was much less than in the control group of patients subjected to operation. PMID- 7990326 TI - [Surgical treatment of late stages of hydronephrosis in children]. PMID- 7990327 TI - [Development of methods of esophagoplasty in children]. AB - In the Clinic of Pediatric Surgery of the Russian State Medical University 310 operations for esophagoplasty were performed using segments of the small and large intestine. The 50-year progress in the creation of an artificial esophagus is characterized by gradual advancement from prethoracic plasty after Roux-Herzen Yudin to the refined method of retrosternal coloesophagoplasty. The incidence of the characteristic postoperative complications reduced by 3 to 10 times, necrosis of the transplant was practically not encountered, the mortality reduced to 1.2%, and the functional results improved significantly. PMID- 7990328 TI - [Thirty years of cryo-ophthalmology. Work dedicated to the memory of Dr. Tadeusz Krwawicz]. AB - It is 30 years since Krwawicz presented a new method of cataract surgery at low temperature. This operation was not only widely accepted, but also showed the possibilities of the use of low temperature in medicine. It soon became apparent that such methods might be helpful in treating a number of eye diseases. This was beginning of a new branch of ophthalmology, cryoophthalmology. The paper presents its development, its position in ophthalmology and the latest achievements. After the 30 years, cryoophthalmology has preserved its importance and its constant evolution; it remains the subject of investigations of many research centres. PMID- 7990329 TI - [Experimental studies on lesions of eye tissues in cobalt intoxication]. AB - The aim of the paper was to examine the influence of cobalt compound on rabbit eye tissues. The lesions in the eyeball were evaluated basing on ophthalmological examination and in light and electron microscopes. The studies revealed that cobalt intoxication caused the following damages in the rabbit retina: oedema and atrophy of nerve fibres, lesions of ganglion, amacrine, bipolar, horizontal cells and nucleus of photoreceptors. Also, obliteration of choroidal vessels and changes in iris and ciliary body were found. Cataract developed in 42% of rabbits and 25% chronic purulent endophthalmitis in 25%. The results of these experimental investigations indicate that further studies on the influence of this metal on human eye tissues are necessary. PMID- 7990330 TI - [Radiometric studies of eye tissues in experimental cobalt intoxication]. AB - Accumulation of cobalt in eye tissues were examined in rabbits which received the radioactive isotope 60Co Cl2. The studies revealed that this metal is accumulated at first in iris, choroid and ciliary body and, in smaller amounts, in cornea, sclera and retina. The least amounts of cobalt were found in lens. The contents of uveal tract was comparable with that found in heart and lungs, i.e. the organs in which lesions are the most frequent in cobalt intoxication. PMID- 7990331 TI - [Influence of steroidal and nonsteroidal anti-inflammatory drugs on post operative blood-aqueous barrier in pseudophakia]. AB - Fluorophotometric evaluation of the tightness of blood-aqueous barrier was made in 2 groups of patients who underwent cataract surgery with IOLs implantation. The first group was treated with nonsteroidal (Naclof, Tolectin) and the second with steroidal (Dexamethasone, Hydrocortisone) anti-inflammatory drugs. Fluorophotometry of the anterior segment of the eye was performed for the quantitative examination of the inflammatory reaction. The leakage of fluorescein through the blood-aqueous barrier was evaluated and compared with the fellow, non operated eye. The individual leakage coefficient, calculated according to Sanders, was lower in the group of patients treated with nonsteroidal drugs but the differences were not statistically significant. The results suggest that nonsteroidal drugs could be as efficient or even more efficient in the treatment of inflammatory reaction after cataract surgery with IOLs implantation. PMID- 7990332 TI - [Efficiency of laser trabeculotomy in open-angle glaucoma]. AB - Results of Nd: YAG laser trabeculotomy performed in 71 eyes of 48 patients with open-angle glaucoma are presented. There were 25 females and 23 males, aged 15-86 years (mean age 67 years). The follow-up was 0.5-1.5 years. Normalization of the intraocular pressure was achieved in 90% of cases and outflow facility was improved in 87.3%. Deterioration of visual acuity was observed in 2.8% of eyes. In 4.2% the procedure was complicated by anterior chamber haemorrhages. The authors discuss principles, indications and techniques of Nd:YAG laser trabeculotomy and compare their results with those of others. PMID- 7990333 TI - [Intraocular lens implantation with circular capsulotomy and "envelope" techniques--comparison of results]. AB - The studies comprised 200 patients with presenile and senile cataract who underwent cataract surgery with IOLs implantation. In 100 consecutive cases circular capsulotomy and in subsequent 100 "envelope" technique were used. The results indicate the advantages of "envelope" method: less intra- and post operative complications, quicker visual convalescence; it is easier and safer. PMID- 7990334 TI - [Evaluation of binocular vision and eye muscle balance in patients with diabetes]. AB - The studies comprised 41 patients, aged 18-67, with type I and II diabetes. The function of ocular muscles was evaluated basing on the examination of eye movements, muscles balance and binocular vision. In 6 patients, binocular vision and in 31 ocular muscles balance were disturbed. No relationship was found between the function of eye muscles and the age of patients, duration of diabetes and changes in the fundus of the eye. PMID- 7990335 TI - [Diagnosis and results of treatment of blow-out fracture of the orbital floor]. AB - In the last 20 years, 273 patients with blow-out fracture of the orbital floor were treated. Surgery was performed in 242 of them (88.6%). The typical features of this type of fracture as well as the methods and results of treatment are presented. Criteria of the recovery were disappearance of diplopia and decrease of enophthalmos. PMID- 7990336 TI - [Post-alcoholic neuropathy of the optic nerve]. AB - The authors presents 36 patients, aged 17-62 years, who, after use of alcohol, developed optic neuropathy in both eyes, causing deterioration of vision of various intensity. In spite of the applied treatment, in 14 cases no improvement of visual acuity was achieved, because of the complete optic nerve atrophy. In the other 12 patients the visual acuity improved but partial optic atrophy with remarkable changes in visual field remained. PMID- 7990337 TI - [Amebic keratitis-keratitis acanthamoeba]. AB - In seventeen patients who suffered of corneal ulcer, and were negative in bacteriological and mycological examinations, parasitological tests were performed between 1990-1992. Acanthamoeba keratitis was diagnosed in one patient with characteristic corneal changes of right eye following trauma. The patient was not a contact lens wearer. The amoeba found in direct smears of scraping from corneal ulcer and isolated and cloned in in vitro conditions (isolate-clone-No. 2961) belonged to Acanthamoeba polyphaga species. The trophozoites showed a low degree of invasiveness and high virulence when tested in BALB/c mice. The authors discussed the epidemiology of Acanthamoeba keratitis and pointed out to the necessity of accurate laboratory diagnosis and discerning interpretation of the results to prevent an Acanthamoeba-phobia among the potential patients and most of all among the medical staff. PMID- 7990338 TI - [Ocular system in Down's syndrome]. AB - The authors presents results of ophthalmological examination of 150 patients with cytogenetically diagnosed Down's syndrome. Refractive errors, requiring correction with glasses, were found in 45.3% of patients. Other ocular changes among which some were qualified for treatment, were observed in 72.7% of cases. PMID- 7990339 TI - [Aschner's cardio-ocular reflex and its importance in eye surgery]. AB - In 113 patients who underwent surgical treatment Aschner's reflex was evaluated by a 24-hours Holter's monitoring and simultaneous registration of the susceptibility for spontaneous bradycardia independent from the time of surgery. Aschner's reflex was found in 43.4% operated patients and bradycardia was statistically significant. Only in the group of children who received atropine intravenously immediately before surgery no statistically significant bradycardia was found. PMID- 7990340 TI - [Familial occurrence of open-angle glaucoma]. AB - Clinical observations of 6 cases of open-angle glaucoma in one family are presented. In this family, in four generations, the total number of glaucomatous persons were 12. Genetic aspects of glaucoma are discussed and it is concluded that all persons with glaucoma should be asked about their family history of eye disease. PMID- 7990341 TI - [Xeroderma pigmentosum--case report]. AB - The authors presented a case of a boy aged 16, in whom xeroderma pigmentosus was diagnosed 6 years earlier. The boy was referred to the clinic on account of a quickly growing tumor of conjunctiva and cornea of his right eye. During 2-year follow-up, in spite of two surgical excision, the tumor relapsed and finally enucleation of the eyeball was performed. Histopathological examination revealed melanoma malignum. The clinical aspects of prophylaxis, early diagnosis and treatment of xeroderma pigmentosum are discussed. PMID- 7990342 TI - [Diagnostics and localization methods of intraocular foreign bodies]. PMID- 7990343 TI - [Various nitrates in the treatment of acute myocardial infarction]. PMID- 7990344 TI - [Surgical treatment of unstable and early post-infarction angina]. AB - Out of 146 patients with unstable and early postinfarction angina pectoris, 120 underwent surgery at various intervals since the condition onset. The patients were followed up from 1 month to 6 years. Surgical management of the above forms of coronary heart disease confirmed its efficacy in prevention of acute, recurrent and repeated myocardial infarctions. PMID- 7990345 TI - [Induracin, prolonged-action nicotinic acid, in the treatment of atherogenic dyslipoproteinemia]. AB - The author presents the results of a cross-over blind trial of induracin, prolonged nicotinic acid. The study covered 31 dyslipoproteinemic patients and lasted 6 months. The treatment gave rise to a significant fall in the total cholesterol, LDL cholesterol, triglycerides (by 11%, 17% and 19% respectively), HDL cholesterol levels went up by 14%, lipid transport proteins proportions changed for the better (AI apoprotein increased by 15% against lowering of apoprotein B by 29%). The drug was well tolerated. PMID- 7990346 TI - [Effect of transcutaneous stimulation of diaphragm on systemic and central hemodynamics in patients with chronic bronchitis]. AB - 25 males and 5 females suffering from chronic obstructive bronchitis (COB) underwent transcutaneous diaphragmatic electrostimulation (TDE). As shown by central intrapulmonary hemodynamics, those patients who had no circulatory decompensation benefited from TDE. There was a decrease in the pulmonary hypertension, intensification of general hemodynamics, reduced tonicity of the pulmonary arteriolar bed, improvement of right ventricular function. In circulatory decompensation TDE may cause deterioration of right ventricular function, enhancement of circulation decompensation against unchanged pulmonary hypertension and pulmonary-arteriolar tonicity. The changes in pulmonary artery pressure, total pulmonary vascular resistance, pulmonary-arteriolar elasticity observed after a single TDE session may prompt the validity of further COB treatment according to the above regimen. PMID- 7990347 TI - [Leukinferon in the treatment of patients with acute viral hepatitis b]. AB - Leukinferon activity was studied in a controlled trial including 30 patients with acute viral hepatitis. The disease ran a moderate severity course in the majority of the patients. Leukinferon, a combined preparation of natural interferon and cytokines produced by virus-induced leukocytes, has marked immunomodulating properties at moderate antiviral activity. Leukinferon was administered intramuscularly for 10 days according to the following scheme: day 1-1 sample 3 times, day 2-1 ampule 2 times, day 3-10-1 ampule a day (overall 1 x 10(5) U of interferon). Due to leukinferon the symptoms of intoxication declined, hepatic biochemistry normalized more rapidly as well as the period of viremia and antigenemia. Positive clinical trends correlated with interferon system improvement and activation of natural killers. 6 months later complete recovery was registered in all leukinferon-treated subjects. PMID- 7990348 TI - [Sneddon's syndrome and Willebrand's factor antigen]. AB - An enzyme immunoassay examination of Willebrand factor antigen (WFA) was conducted in 36 patients with Sneddon's syndrome. The syndrome in 25 females and 11 males (mean age 40 years) was mainly characterized by ischemic cerebrovascular disorders in combination with advanced skin livedo. All the patients were not in an acute stroke phase. Increased WFA (above 2 IU/ml) occurred in 12 (33%) patients. Clinical manifestations, the condition severity, incidence of phospholipid antibodies, CIC levels in them were similar to those in patients with normal WFA values. The thrombotic trend in Sneddon's syndrome may result in some cases from structural endothelial damage responsible for WFA levels elevation, while under normal WFA content endothelial cell function may be affected. PMID- 7990349 TI - [Stomach neoplasms morbidity]. PMID- 7990350 TI - [Familial systemic lupus erythematosus]. PMID- 7990351 TI - [Clinical significance of hyperuricemia in psoriasis]. AB - After analysis of 1146 psoriasis patients, high incidence of asymptomatic hyperuricemia (18.8%) and elevated average levels of uric acid in these patients' blood were confirmed (346.8 +/- 2.4 mumol/l). More severe forms of uric acid disbolism lead to aggravated skin affections (psoriatic erythrodermia, exudative psoriasis), arthritis, occur in familial predisposition to psoriasis. Advanced psoriasis patients are at risk to develop apparent gout. PMID- 7990353 TI - [Ultra-low magnetic resonance tomography of thoracic and lumbar spine osteochondrosis]. AB - The paper presents the results of tomographic studies of 119 patients with clinical manifestations of radiculopathy or radiculomyelopathy. MR tomography was performed on the Magnaview unit ("Instrumentarium", Finland) at field intensity 0.04 T. The analysis of T1- and T2-weighted sagittal tomograms providing MRT picture of osteochondrosis and various hernias shows that osteochondrosis involves several disks simultaneously while their bulging towards the vertebral canal is multiple. The severity of the hernia in some cases does not closely agree with degeneration degree or the decline of the vertebral disk height. However there is a close correlation between the size and direction of the hernia on the one hand and the clinical manifestations on the other hand. PMID- 7990352 TI - [Hypophyseal hormones in young patients with breast cancer]. AB - Hypophyseal hormones were studied in comparison with cellular and humoral immunity in young and middle aged females with breast cancer and controls matched by age. No correlation existed between LH concentrations and cellular, humoral immunological parameters in young breast cancer patients. Basal secretion of FSH directly correlated with the activation markers expression (antigens CD30, CD38) only in young patients. Prolactin concentration was negatively related to B-cell marker (mu-chain IgM) and expression of adhesion molecules (antigen CD11b) in the young, while in the middle-aged to mature T-cell levels only (antigen CD3). No age-specific correlations were found between immunological parameters and ACTH basal secretion, except direct relationship with CD11b-positive cells expression in middle-aged subjects. PMID- 7990354 TI - [Pathogenesis of anemia in systemic scleroderma]. AB - The paper reports a case of anemia with complicated genesis in a male patient with systemic scleroderma (SS). Antianemia therapy was not easy, as after rapid disappearance of iron deficiency vitamin B12 deficiency remained, hemolytic component of the disease persisted. The case demonstrates that multicomponent pathogenesis of anemic conditions is possible. This must be taken into consideration when planning therapeutic policy in SS. PMID- 7990355 TI - [Effect of hyperbaric oxygenation on the dynamics of carbohydrate and lipid metabolism in the blood of patients with type I diabetes mellitus]. PMID- 7990356 TI - [Hemodynamic changes in patients with large postoperative ventral hernias]. AB - Hemodynamic parameters have been analyzed in 68 inpatients with large postoperative ventral hernia. Most of the patients showed normodynamic circulation. The artificial rise of the intra-abdominal pressure in the course of the preoperative preparation induced hypodynamic response of the cardiovascular system. Early after the surgery, the patients had hypodynamic circulation. As compared to induced abdominal hypertension, this hypodynamia was less pronounced indicating adaptation of the cardiac activity to preoperative hypertension. This is confirmed by the absence of complications related to high intraabdominal pressure in early postoperative period. PMID- 7990357 TI - [Diagnosis of Rothmann-Makai panniculitis]. PMID- 7990358 TI - [Zollinger-Ellison syndrome]. PMID- 7990359 TI - [Myocardial disorders after combined treatment of lymphogranulomatosis]. PMID- 7990360 TI - [Rapidly progressing clinical course of Burger's disease]. PMID- 7990361 TI - [Statistics on the risk factors in the development of cholelithiasis]. PMID- 7990362 TI - [Hypertrophic osteoarthropathy and lung cancer]. PMID- 7990364 TI - [Comment on the article of D.S. Sarkisov "Is it valid to consider so-called iatrogenic diseases"]. PMID- 7990363 TI - [Acute adult respiratory distress syndrome]. PMID- 7990365 TI - [Clinical classification of herpes zoster]. PMID- 7990366 TI - [Methodologic approaches to the evaluation of effectiveness of medical postgraduate medical education]. PMID- 7990367 TI - [Microwave resonance therapy in the treatment of patients with duodenal ulcer]. AB - Microwave resonance treatment (MRT) of duodenal ulcer leads to normalization of relationships between aggressive and defense ulcerogenesis factors. This combines with activation of reparative regeneration of the ulcer lesion. There appears a tendency to a decline in pepsin and hydrochloric acid secretion in the gastric juice, plasmic gastrin concentrations decrease more noticeably, production of protective glycoproteins of the gastric mucus grows as well as of E 2 prostaglandins and plasmic secretin. Typical changes in the quantities of plasmic bombesin, vasoactive intestinal polypeptide (lowering) and gastroinhibitory polypeptide (rising) in the MRT course allow prognostication of case-by-case responses. The highest sensitivity to MRT was observed in functional regulatory biochemical systems (neuropeptides, hormones) of the APUD series. Their reaction to MRT served the basis for biochemical typing of the patients and MRT outcome prognostication. PMID- 7990368 TI - [High-energy laser irradiation in the combined treatment of duodenal ulcer]. AB - Combined treatment of 149 patients with duodenal ulcer included a course of endoscopic irradiation emitted by a copper laser. The ulcers healed in all the cases, complicated with hemorrhages among them. In the exposure to green-and yellow light in day intervals cicatrization occurred within treatment day 11.6 +/ 0.6, on the average. Separate use of green and yellow light gave similar results. For controls respective days were 27.2 +/- 1.3. The above multimodality treatment with laser resulted in 5 year relapse-free intervals in 43% of those treated against the absence of relapse-free patients 3 years after the start of drug monotherapy. PMID- 7990369 TI - [Ultrasonography in the diagnosis of complications caused by cholelithiasis]. AB - The authors presented the results of ultrasonic investigation of 201 patients with cholelithiasis that were confirmed during surgery. Concurrent acute or chronic inflammations and hydrops of the gallbladder were found to be the commonest complications. More rare but dangerous complications were cholecystempyesis, wall destructions or paravesical abscess. Echographical symptoms of the complications mentioned were presented as well. The informative value of ultrasonic investigation turned to be rather high: the USI data coincided with operative findings in 98% of the patients. PMID- 7990370 TI - [Effect of smoking in basal, vagus and and maximal stimulated gastric secretion of hydrochloric acid and pepsin]. PMID- 7990371 TI - [Laboratory diagnosis of disseminated intravascular blood coagulation syndrome in patients with rheumatoid arthritis]. AB - DIC-syndrome frequently associated with anemia is one of rheumatoid arthritis complications which runs latently in the presence of hypercoagulation and low fibrinolytic activity. The development of DIC syndrome in the above patients correlates with the process activity, pattern of the disease, is independent of rheumatoid arthritis stage and duration, the patients' age, immunological and serological characteristics. Concentrations of circulating immune complexes and DIC-syndrome are related in rheumatoid arthritis patients with anemia. PMID- 7990372 TI - [Genetic and phenotypic markers in adult leukemia]. AB - The authors studied a number of original genetic phenotypical markers in leukemia patients. They suggested the existence of polygenic impacts involved in leukemia genesis. Hence, leukemias may be linked with some gene markers. It was established that leukemic subjects had phenotypical frequencies of cerebral hemispheric and sighting eye asymmetry, density of ear wax, hair color significantly different from those in the population. Hence, the above markers may indicate individual predisposition to leukemias. PMID- 7990373 TI - [Treatment of iron-deficiency anemias and latent iron deficiency with mineral water of the sanatorium "Martsialnye vody"]. PMID- 7990374 TI - [Clinical plasmapheresis in the treatment of diabetic neuropathy]. PMID- 7990375 TI - [Effect of veroshpiron on hormone level in patients with Parkinson's disease]. AB - Blood hormones and urinary excretion of corticosteroids were measured in 39 parkinsonian patients receiving chemotherapy with adjuvant 3-week course of verospiron (50-100 mg/day). The latter promoted normalization of endocrine and clinical statuses in the majority of the patients. It is suggested that the response may be obtained via neuropeptide systems of the brain. PMID- 7990376 TI - [Paraneoplastic syndrome in the clinical course of lung cancer]. PMID- 7990377 TI - [Long-term anamnesis of idiopathic fibrosing alveolitis]. PMID- 7990378 TI - [A case of eosinophilic fasciitis]. PMID- 7990379 TI - [Two cases of hyperkinetic syndrome in erythremia]. PMID- 7990380 TI - [Cryoglobulinemia in the patient with ascaridiasis]. PMID- 7990381 TI - [Methods of the methotrexate utilization in rheumatoid arthritis]. PMID- 7990382 TI - [Blood rheology in the early stages of cerebrovascular insufficiency]. PMID- 7990383 TI - [Errors in the diagnosis of liver diseases]. PMID- 7990384 TI - [Immunotherapy of complications caused by Pseudomonas aeruginosa]. PMID- 7990385 TI - [Complications of subclavian vein catheterization]. PMID- 7990386 TI - [Etiotropic therapy of tick-borne borreliosis (Lyme disease)]. PMID- 7990388 TI - [Rationale for pathogenesis of ulcer disease (Dedicated to academician V.Kh.Vasilenko)]. PMID- 7990389 TI - [The 4-th International Congress on esophageal mucosa diseases]. PMID- 7990390 TI - [Russian conference "Current aspects of prevention of non-infectious diseases"]. PMID- 7990387 TI - [Approaches to the personal antianginal therapy. Can we consider nitrosorbide as a drug of choice?]. PMID- 7990391 TI - [Avgustin Nikolas Zhilber (1858 - 1927)]. PMID- 7990392 TI - [F.A. Giltebrandt - outstanding Russian surgeon and clinician]. PMID- 7990394 TI - [Mobbing: psychological terrorist at the workplace. Disease-producing chicaneries]. PMID- 7990393 TI - [Characteristics of cerebral circulation and its disorders in arterial hypertension]. PMID- 7990395 TI - [Primary nursing--also on your ward?]. PMID- 7990396 TI - [Depression: symptoms, risk factors, explanatory models. The quiet disorder: depression]. PMID- 7990398 TI - [Plebiscite of December 4th. The new health insurance legislation]. PMID- 7990397 TI - [Use of flowers in nursing practice. Flower extracts for the ailing soul]. PMID- 7990399 TI - [Success with outpatient night nursing in Lucerne. Home care round the clock works]. PMID- 7990401 TI - [Real listening]. PMID- 7990400 TI - [Gentle persuasion]. PMID- 7990402 TI - [Health center for asylum seekers in Genevea. Health Center for Migrants]. PMID- 7990403 TI - [Outpatient care of cancer patients. Evaluation of pain in the home]. PMID- 7990404 TI - [Approaching death with serenity]. PMID- 7990405 TI - [Long-term admission of psychiatric patients. Finding the cruise rhythm]. PMID- 7990406 TI - [The new Federal Health Insurance Legislation]. PMID- 7990407 TI - [Incontinence--an avoidable fate]. PMID- 7990409 TI - [The business with "Adam"]. PMID- 7990408 TI - [From theoretical primary nursing to the real thing. Motivated nurses, satisfied patients]. PMID- 7990410 TI - [Prevention of thrombosis]. PMID- 7990412 TI - [Effects of preoperative parenteral feeding]. PMID- 7990411 TI - [Diagnosis and therapy of migraine]. PMID- 7990413 TI - [Cardiomyopathies--etiology, clinical aspects and therapy]. PMID- 7990414 TI - [Deviltries in the work place]. PMID- 7990415 TI - [The rightness of prejudice]. PMID- 7990416 TI - [The psychology of nursing personnel in ambulatory care]. PMID- 7990417 TI - Multi-disciplinary approach to cranial base tumors. PMID- 7990418 TI - The management of non-melanoma skin cancer of the head and neck. PMID- 7990419 TI - Comprehensive care of the cleft lip and palate patient. PMID- 7990420 TI - Otitis media: when are tubes and/or adenoidectomy needed? PMID- 7990421 TI - Hearing aids: selection, parameters, & limitations. PMID- 7990422 TI - Cochlear implants. PMID- 7990423 TI - Snoring and sleep apnea: evaluation and treatment. PMID- 7990424 TI - Common voice disorders. PMID- 7990425 TI - Options in cosmetic rehabilitation of the aging face. PMID- 7990426 TI - Evaluation of the neck mass. PMID- 7990427 TI - The evaluation and diagnosis of the dizzy patient. AB - In conclusion, the assessment of the dizzy patient is indeed complex and far reaching. The expertise of family practitioners, internist, neurologists, otolaryngologists, and neurosurgeons at times is essential and one should not feel inhibited about referring the patient for further evaluation to our colleagues so that the patient may best be served and resolution of the patient's complaints may result. PMID- 7990428 TI - Ethics, values, and policy decisions for children with disabilities: what are the costs of political correctness? PMID- 7990429 TI - Health status and income: the impact of poverty on child health. PMID- 7990430 TI - Health care reform: what's in it for children with chronic illness and disability. PMID- 7990431 TI - Child disabilities: who's in, who's out. PMID- 7990432 TI - Integrating services: the case for better links to schools. PMID- 7990433 TI - A program to address the special needs of drug-exposed children. AB - The Ravenswood-Stanford Coalition for At-Risk Children promotes school success by intervening with K-3 students identified as drug-exposed, either prenatally or environmentally, enabling them to remain in regular classrooms rather than diverted to special education. This goal was accomplished through professional partnerships, home involvement, individual intervention plans, special school based services, and mentorships. Results from the project indicate these children are not significantly different from their peers; home involvement promotes better school linkages and reinforces positive behavior change; appropriate short term, school-based services can increase academic and behavioral performance; dedicated volunteers working individually with students accelerate change processes; and these special at-risk students must be assigned to caring, supportive, and predictable classrooms. PMID- 7990434 TI - Prenatal drug education in public and private schools of Nebraska. AB - Substance abuse during pregnancy continues to be a serious health problem in the United States. Hazards associated with the use of alcohol, tobacco, and other drugs by pregnant women have been documented. The extent to which prenatal drug education is included in school health education has not been addressed. This survey determined the nature and extent of prenatal drug education being conducted by Nebraska school teachers in health-related fields. Educators in public and private schools who teach health-related courses were surveyed. Respondents indicated prenatal drug education is being addressed in a variety of courses. Amount of time devoted to the topic was 2.68 hours overall. Problems associated with providing prenatal drug education included inadequate teacher knowledge and training, lack of appropriate materials, and time limitations in the curriculum. Implications for comprehensive school health education are identified. PMID- 7990435 TI - Health services for special needs children in Pennsylvania schools. AB - School health programs traditionally have involved health services, health instruction, and a safe school environment. Likewise, school health services have been provided by nurses, physicians, and appropriate administrative personnel. In the 1990s, increased integration of primary care services through school-based clinics expanded traditional activities of school health programs. Consequently, more chronically ill children, particularly technology dependent children, have entered the regular school setting, requiring that schools be prepared to manage these chronically ill students who come to school with new morbidities and technological dependencies. This statewide survey examined the number and kind of special needs children in the regular school setting in Pennsylvania, as well as the personnel, programs, policies, and resources available to support these children. PMID- 7990436 TI - Secondary health educators' perceived self-efficacy in teaching mainstreamed mentally disabled students. AB - This study examined secondary school health education teachers' perceived adequacy of professional training and perceived self-efficacy in teaching mainstreamed mentally disabled students (MMDS). Subjects included a stratified random sample (N = 333; response rate = 63%) of secondary school health education teachers in nine states which require that health education be taught in the schools. Subjects were 44% female, 92% White, had a mean age of 40.6 years (SD = 8.6) and a mean of 12.1 years (SD = 7.5) of teaching experience. One in four received no training on teaching MMDS. Efficacy expectation (EE) scores were significantly higher in teachers with some training in teaching MMDS (p < .001) but outcome expectation (OE) scores were not significantly different based on training. Also, EE and OE scores were higher in teachers who perceived the need for health knowledge and skills (outcome value) as greater in this population (p < .001). A significant correlation existed between the degree of reward in teaching MMDS and EE and OE (p < .01). Fifty-four percent believed materials available for teaching this group were inadequate; however, 77% reported that there special education department was supportive in material development. PMID- 7990437 TI - Lessons from controversy in applying universal precautions for HIV/AIDS. PMID- 7990438 TI - Reversed-phase solvent-gradient HPLC retention indexes of drugs. AB - A high-performance liquid chromatographic (HPLC) system has been developed in which ionized basic drugs and nonionized drugs elute in efficient and reproducible bands. The effects of different HPLC systems and solvent-gradient rates on the reproducibility of retention times and normalized retention data were investigated. The retention indexes of 469 drugs were determined on this system and compared with the retention indexes of drugs in common from a previously reported retention index database. PMID- 7990439 TI - Urinary screening for benzodiazepines with radioreceptor assay: comparison with EMIT d.a.u. benzodiazepine assay and high-performance liquid chromatography. AB - The radioreceptor assay (RRA) provides a total estimate of all pharmacologically active forms of benzodiazepines and their metabolites. We evaluated the method for urine drug screening. Detection limits of the most commonly used benzodiazepines and their major metabolites were determined. In all cases, the detection limits were lower than the cutoff values specified for the Syva EMIT d.a.u. benzodiazepine assay. Thirty-three urine samples for routine drug screening were tested for benzodiazepines by RRA and EMIT. Results were compared with those obtained by a highly specific high-performance liquid chromatographic (HPLC) method. Five commonly used benzodiazepines and their major metabolites were identified by use of a computerized multichannel photodetector. We obtained two false-negative results by RRA when compared with HPLC. These may be caused by conjugate formation. The inclusion of a simple enzymatic hydrolysis improves the detection of compounds excreted in the urine as glucuronide conjugates (e.g., oxazepam). We conclude that the combination of enzymatic hydrolysis and direct RRA provides a rapid and acceptable method for detection of the presence of benzodiazepines in urine samples. PMID- 7990440 TI - Determination of cocaine usage in pregnant women by a urinary EMIT drug screen and GC-MS analyses. AB - In mothers who had no prenatal care and in their newborns, the presence of cocaine and benzoylecgonine (BE) was determined in urine, hair, and meconium. Samples of urine and hair were obtained from pregnant women who entered the hospital for delivery. Cocaine usage was assessed by a urinary enzyme-multiplied immunoassay technique (EMIT) and by gas chromatography-mass spectrometry (GC-MS). GC-MS was used to detect the presence of cocaine and BE in maternal urine and hair and in meconium and hair obtained from their newborns. In this study of 40 women, the EMIT assay for urinary BE identified 17 (42.5%) of the women as having used cocaine. Of these 17 women, all of their newborns were exposed to cocaine during gestation, based on the analysis of neonatal hair and meconium for cocaine or BE. From the maternal samples that were assayed for cocaine and BE by GC-MS, it appears that hair analysis identified the most cocaine users (70%) of the 40 women who participated in the study. When GC-MS was used to analyze the various samples from mothers and their newborns, 80% of the neonates showed exposure to cocaine. This study shows that women with no prenatal care who have a positive urinary drug screen by EMIT for BE have exposed their newborns to cocaine. The data from pregnant women with a negative drug screen for BE show that 52.2% of their newborns had prior fetal exposure to cocaine. PMID- 7990441 TI - Stable-isotope dilution GC-MS for determination of toluene in submilliliter volumes of whole blood. AB - An accurate and sensitive yet simple protocol for the analysis of toluene in submilliliter quantities of whole blood using stable-isotope dilution GC-MS has been developed and evaluated for use in pharmacokinetic studies of toluene exposure. The method involves the use of toluene-d8, a relatively inexpensive chemical used as a solvent for nuclear magnetic resonance spectroscopy, as an internal standard and extraction with pentane. This procedure allows for the determination of toluene in whole blood down to approximately 5 ng/mL and is suitable for pharmacokinetic measurements and biomonitoring of exposure to toluene. PMID- 7990442 TI - Simple and rapid HPLC of quinine, hydroxychloroquine, chloroquine, and desethylchloroquine in serum, whole blood, and filter paper-adsorbed dry blood. AB - A simple high-performance liquid chromatographic assay for the measurement of quinine, hydroxychloroquine, chloroquine, and desethylchloroquine in small volumes (50-200 microL) of serum, whole blood, or filter paper-adsorbed dry blood was developed. The analytes are isolated by liquid-liquid extraction and chromatographed on a sulfophenylpropyl-modified silica column under isocratic conditions. The column effluent is monitored by fluorimetry (excitation wavelength, 215 nm; no emission filter). The limit of quantitation is 0.005-0.01 mg/L for chloroquine and hydroxychloroquine and 0.05 mg/L for quinine. No interference from other antimalarial drugs or other compounds commonly used has been observed. Quantitative results can be obtained within 1 hour of receipt of the sample. PMID- 7990443 TI - Improved procedure for the high-performance liquid chromatographic determination of monohydroxylated PAH metabolites in urine. AB - An improved high-performance liquid chromatographic (HPLC) method for the determination of 3-hydroxybenzo(a)pyrene (3-OHBaP) in urine was developed. The sensitivity and reproducibility of the technique was greatly improved by the addition of 1 mg/L ascorbic acid to the methanol eluent of the HPLC system. This procedure also eliminated the peak splitting and band broadening of the 3-OHBaP peak otherwise observed. Furthermore, it corrected the urine matrix effect on the slope of standard curves. In fact, in the absence of ascorbic acid in the HPLC system, slopes of standard curves were steeper when prepared in a methanolic extract of control rat urine (121 L.nmol-1) than in methanol only (86 L.nmol-1). Both these slopes were smaller than that obtained with the modified mobile phase (244 L.nmol-1). The effect of the latter on the shape and intensity of the 1 hydroxypyrene (1-OHP) chromatographic peak was also investigated. Again, slopes were greater when the standards, prepared in a methanolic extract of urine, were chromatographed with ascorbic acid (380 L.nmol-1) than without (157 L.nmol-1). Therefore, it seems that ascorbic acid, like certain substances in urine, may act by masking specific adsorption sites--probably uncapped silanol residues on the LC 18 column that can retain free 3-OHBaP and 1-OHP metabolites. PMID- 7990444 TI - Urinary methamphetamine concentration following famprofazone administration. AB - A 37-year-old man had a considerable concentration of methamphetamine in his urine, but he denied taking any abused drug. It was found that he took a pain killer that contains famprofazone, a relatively strong analgesic whose metabolites include methamphetamine and amphetamine. The human urinary metabolism of famprofazone was investigated. Immunoassay was used as a preliminary test, and gas chromatography with flame-ionization detection and gas chromatography-mass spectrometry were used for quantitation and confirmation. PMID- 7990445 TI - Automated Cobas Mira kinetic enzymatic assay for ethylene glycol applied to emergency situations. AB - An automated kinetic method for assaying ethylene glycol in serum using glycerol dehydrogenase with the multiparametric analyzer Cobas Mira is described. Initially, 5 microL of sample is mixed with tris-NAD buffer; after enzyme addition, the variation of the absorbance at 340 nm is automatically measured, and the instrument calculates the ethylene glycol concentration of the specimen. The method has good precision and specificity and is suitable for emergency screening. Some applications developed in our laboratory are also described. PMID- 7990446 TI - Distribution of sertraline in postmortem cases. AB - Sertraline is a potent inhibitor of serotonin reuptake in the central nervous system and is used clinically to treat depression and obsessive-compulsive behavior. Over the course of one year, there were seven cases investigated by the Office of the Chief Medical Examiner, State of Maryland, in which sertraline was identified in postmortem specimens. Heart blood concentrations in the seven cases ranged from 0.23 to 0.46 mg/L; desmethylsertraline concentrations ranged from 0.08 to 0.99 mg/L. One similarity with tricyclic antidepressants is the high liver concentrations of drug and metabolite relative to the blood. One unusual finding is the small concentrations of drug and metabolite in the urine relative to other specimens. In none of these cases was the cause of death related to sertraline intoxication. PMID- 7990447 TI - Determination of tetramine in postmortem specimens by GC-NPD. AB - A method for the determination of tetramine in postmortem specimens is reported. Tetramine is an organosulfur rodenticide. Parathion, an organophosphorous insecticide, was adopted as the internal standard. Both were extracted from biological materials by benzene and purified by an aluminum oxide column. The extract was analyzed by a gas chromatograph equipped with a nitrogen-phosphorous detector. The extraction efficiency was greater than 90%, and the limit of detection was 0.05 microgram/g for the liver. The standard curve was linear in the range 0.5-50 micrograms/g for the liver, and the correlation coefficient was equal to 0.9993. PMID- 7990448 TI - Drugs-of-abuse testing in urine: statistical approach and experimental comparison of immunochemical and chromatographic techniques. AB - This study deals with the experimental and statistical comparison of six immunochemical techniques, including noninstrumental on-site and instrumental formats (EIA-EMIT and EZ-SCREEN; FPIA-ADx; RIA-Coat-A-Count; LI-Abuscreen ONTRAK; CBI-Triage), and three chromatographic techniques (TLC-Toxi-Lab; HPLC; HPLC REMEDi drug profiling system), using GC-MS as a reference technique for analyzing amphetamines, barbiturates, benzodiazepines, cannabinoids, cocaine, methadone, and opiates in the urine of various kinds of drug users. The study reports (a) the values of sensitivity, specificity, false-positive rates, and false-negative rates of each technique; (b) the results of bayesian statistical analysis, which are based on prevalence values of the samples examined and expressed as positive and negative predictive values and cumulative predictive values for each single technique and for combinations of paired immunochemical and chromatographic techniques; and (c) the results of a rough classification of the various degrees of predictability of these techniques. Lastly, this study proposes a decision making process for establishing the best combination of analytical techniques for the goals in question, according to the characteristics and facilities of each laboratory. PMID- 7990449 TI - Salting-out effect of sodium fluoride and its influence on the analysis of ethanol by headspace gas chromatography. PMID- 7990450 TI - Analysis of morphine and amphetamine in meconium with immunoassay and HPLC-diode array detection. PMID- 7990451 TI - Evaluation of a multidisciplinary treatment approach in an inpatient geropsychiatric unit. PMID- 7990452 TI - Effectiveness of an inpatient geriatric service in a university hospital. AB - OBJECTIVE: To assess the effectiveness of an acute interdisciplinary inpatient geriatric service in a university hospital. DESIGN: Prospective randomized control study. SETTING: Large urban university hospital. PATIENTS: 40 consecutive inpatients, randomized for inclusion on the geriatric service (study patients, n = 20) or to continue usual hospital care (control patients, n = 20) from among the geriatric consult population. MAIN OUTCOME MEASURES: Subjects were followed for changes in length of stay, hospital costs, diagnostic testing, pharmacy use, functional status, discharge disposition, and readmission within 30 days after hospitalization. RESULTS: Mean age of patients study 79.2 years (control 73.9 years). Sixty percent of study patients went home and 30% to nursing homes (control 20% home, 65% nursing homes) P = .03. Total length of stay mean 20.3 days study (control 32.7 days), length of stay after randomization mean 7.7 days study (control 11.2 days), mean overall hospital costs $23,906 study (control $45,189), and mean hospital costs after randomization study $4,671 (control $9,404) were not significantly different by F-tests due to wide variability. Laboratory use was reduced with mean 4.4 tests study (control 16.9) P = .01 and mean laboratory costs $263 study (control $828) P = .02. Functional ability improved (scale 1-7) with mean improvement study 0.8 (control 0.3) P = .09. Mean number of medications were lower in the study group by 30% P = .02; mean cost of medications at discharge was reduced with study $38 (control $112); and mean pharmacy charges after randomization decreased $462 study (control $1,268) P = .06. Readmission 30 days after discharge was not significantly different (study 21%, control 33%). CONCLUSIONS: An interdisciplinary acute geriatric service can be cost effective in providing care to elderly patients in a university hospital. It can improve outcomes measured by decreased laboratory and pharmacy usage, improved functional status, and discharge to a lesser level of care without increasing length of stay or early readmission after discharge. PMID- 7990453 TI - Fat embolism. PMID- 7990455 TI - Health consultations in the Division of Environmental Epidemiology. PMID- 7990454 TI - Agranulocytosis in a hyperthyroid patient. PMID- 7990456 TI - Family violence: reaching out to stop the abuse. PMID- 7990457 TI - Limited liability companies: the entity-of-choice is now available for Tennessee physicians. PMID- 7990458 TI - Fright. PMID- 7990459 TI - An anachronism in the new health care system. PMID- 7990460 TI - Managed care. PMID- 7990461 TI - When alcohol and water don't mix: diving under the influence. AB - The impairing effects of alcohol on divers' abilities to perform shallow-water entry dives were investigated under controlled conditions. Each of 13 male recreational divers, 21 to 35 years old, performed three shallow-entry dives during each of seven diving sessions at various blood alcohol concentrations (BACs). The mean group BACs of Diving Sessions 1-7 were 0, 17, 40, 71, 100, 123 and 97 mg/dl, respectively. Diving performances were videotaped and rated on their relative risk of injury due to contact with the pool bottom if the depth had actually been 3.5 feet. The data indicate progressive and significant impairment of diving performance at BACs of 40 mg/dl (or 0.04 g/dl, or 0.04%) and higher. Corroborating evidence of alcohol impairment was obtained from administering Field Sobriety Tests following Sessions 1, 5, 6 and 7; almost all subjects failed the tests at the higher BAC sessions. An analysis of the self ratings of diving performances indicated that the divers were not aware of either their degraded performance or the increased risk of injury resulting from diving after drinking. PMID- 7990462 TI - Expectancy theory: a two-process model of alcohol use and abuse. AB - In recent years, cognitive-behavioral approaches to drinking behavior have postulated the importance of alcohol expectancy and drinking refusal self efficacy in the development and maintenance of problem drinking. However, despite a growing number of publications, the structure and role of these constructs have not been clearly explicated in theoretical terms to date. This article proposes a two-process theory of alcohol use and abuse. It is suggested that the acquisition and maintenance phases of drinking behavior are governed by different principles of learning and involve different decision-making processes. The acquisition phase is though to be a time of instrumental learning, in which decision making involves controlled processing by means of a kind of "mental algebra". The maintenance phase is described as subject to the principles of classical conditioning, with automatic processing playing a major role in the making of decisions. Integral to both phases, though differing in structure and function from the first to the second, is the concept of alcohol expectancies. Another cognitive construct, drinking refusal self-efficacy, is also hypothesized to play a role in decisions to drink or not to drink. It is suggested that the development of drinking behavior is best explained in terms of associative models of learning and memory. Implications for prevention and treatment of problem drinking are discussed. PMID- 7990464 TI - Negative and positive alcohol expectancies as predictors of abstinence after discharge from a residential treatment program: a one-month and three-month follow-up study in men. AB - Male alcohol dependent clients (N = 53), who were given the Alcohol Expectancy Questionnaire and the Negative Alcohol Expectancy Questionnaire upon admission to a residential alcohol treatment program, were successfully followed-up 1 month and 3 months after discharge to assess their compliance with the treatment goal of total abstinence. At 1 month, neither demographic variables nor alcohol expectancies were associated with outcome consumption. At 3 months, however, the demographic variable, age, total negative expectancy (but not total positive) and the two subscales, global positive expectancy and continued-drinking negative expectancy (representing longer term expected negative consequences), were. The potential importance of negative alcohol expectancy in drinking decisions and the limitations of the study were identified. PMID- 7990463 TI - Modifying alcohol-related expectancies in grade-school children. AB - Expectancies for reinforcement from alcohol appear to form during the grade school years and play a causal role in problem drinking behavior. Using a sample of 268 second through fourth graders, we investigated whether children's expectancies could be modified successfully. Children were randomly assigned to one of four conditions: two experimental expectancy modification conditions (using 10-minute video interventions), one control condition involving a 10 minute video presenting facts concerning alcohol's deleterious effects, and one no-intervention control condition. Relative to controls, expectancies were increased by one experimental condition and decreased by the other; these changes were sustained at 4-week follow-up. This suggests expectancy modification should be tested as an adjunct to current prevention programs. Relations of gender and family history of problem drinking or alcoholism to expectancy endorsement are described. PMID- 7990465 TI - State variations in public and private alcoholism treatment at specialty substance abuse treatment facilities. AB - This article reports characteristics of state specialty alcoholism treatment systems estimated from the 1989 National Drug and Alcohol Treatment Unit Survey (Ndatus). Ndatus is adjusted to correct for item nonresponse and differential unit nonresponse across states. We estimate that $3.8 billion was spent nationally on specialty alcoholism treatment in 1989. Per capita funding ranged from $52 in Alaska to $6 in Mississippi. Clients in treatment per capita and funding per client-day each varied more than 10-fold across states. Comparison of treatment system measures with indicators of the need for alcoholism treatment showed little systematic relationship across states. PMID- 7990467 TI - Characteristics of alcoholics who attempted suicide: co-occurring disorders and personality differences with a sample of male Vietnam era veterans. AB - Data from the Vietnam Experience Study were used to examine differences among alcoholic suicide attempters and alcoholic nonattempters with regard to co occurring psychiatric disorders and MMPI scale scores. Comparisons between the 83 alcoholic suicide attempters and the remaining 978 alcoholic nonattempters indicated that suicide attempters had significantly higher rates of co-occurring disorders as well as an MMPI-based personality pattern characterized by higher levels of pathology. A discriminant function analysis yielded an overall classification accuracy of 74.08%, with significant MMPI scale scores suggestive of personality differences in impulsivity, destructiveness and assaultiveness (especially code 4-9-6). Suicide attempts may be a manifestation of self destructive behavior that typifies a subset of alcoholics with pervasive difficulties. PMID- 7990466 TI - Rates and predictors of four-year readmission among late-middle-aged and older substance abuse patients. AB - This naturalistic study examines treatment, diagnoses and readmission among late middle-aged and older (age 55+) substance abuse inpatients (N = 16,066) in Department of Veterans Affairs Medical Centers. Over an interval extending from 4 years before to 4 years after an index episode of care, older substance abuse patients used substantial amounts of inpatient and outpatient treatment. Service use was heaviest among patients with a concomitant psychiatric disorder, and there was no evidence that it declined over time in the overall group. Four-year readmission rates in three diagnostic subgroups (alcohol or drug dependence diagnosis only, alcohol or drug psychoses, substance dependence and/or psychoses with one or more psychiatric diagnoses) were very high (57% to 70%); however, they were somewhat lower among patients with less chronic substance abuse problems. Readmission and multiple readmission were predicted by younger age, unmarried status, more prior service use, alcohol psychosis or psychiatric diagnoses, treatment in a psychiatric unit, and shorter hospital stay. These factors may be used at admission and discharge to identify patients at risk for rehospitalization; inpatient treatment and aftercare can be planned accordingly. PMID- 7990468 TI - A prospective study of the precursors to problem drinking in young adulthood. AB - This study was part of the Jyvaskyla Longitudinal Study on Social Development. The subjects (196 males, 173 females) were studied at age 8, 14 and 26. Three components in drinking habits were obtained at age 26: social, problem and controlled drinking. Moderate to severe problem drinking was obtained for 26% of the men and 1% of the women, and mild problem drinking for 23% of the men and 15% of the women. Problem drinking (defined by the CAGE Questionnaire, arrest for alcohol abuse and other indicators of heavy drinking) was directly accounted for by poor school success at age 14 and, for men, by conduct problems and low anxiety. Variables at age 8 that contributed indirectly to adult problem drinking were aggression, low anxiety, low prosociality and poor school success for men, and high anxiety and poor school success for women. Women and men differed in the effect of social anxiety; in men, anxiety was a protective factor against problem drinking; in women, it was a risk factor. Although conduct problems often precede severe problem drinking, other risk factors may exist among sons of alcoholic parents. Parental drinking had a significant threshold effect on male off springs' drinking: if parental drinking was low, there was less problem drinking among the male offspring than if a mild dependence on alcohol was observed in the parents. PMID- 7990469 TI - The effects of family cohesiveness and peer encouragement on the development of adolescent alcohol use: a cohort-sequential approach to the analysis of longitudinal data. AB - This article demonstrates a latent growth curve methodology for analyzing longitudinal data for adolescent alcohol use by combining information from different overlapping age cohorts to form a single developmental trajectory. Hypotheses concerning the form of growth in alcohol use, the extent of individual differences in the common trajectory over time, and covariates influencing both initial status and the form of growth were tested. Utilizing five separate age cohorts each measured over the same 4-year period, results suggested a common trajectory existed across the 8 years represented by the cohort-sequential analysis, with alcohol use increasing more rapidly during the adolescents' transition to high school. Family cohesion and peer encouragement for alcohol use were hypothesized to influence both initial status and the trajectory of alcohol consumption during adolescence. While family cohesion served to suppress initial levels of consumption delaying the upward trajectory of alcohol use, peer encouragement was related not only to initial, and elevated, levels of use, but was predictive of those changes that occurred during adolescence. Discussion involves the importance of family and peer influences in the development of adolescent alcohol use and the utility of the cohort-sequential approach in the analysis of longitudinal data. PMID- 7990470 TI - Adult daughters of alcoholics: are they unique? AB - To test the assertion in the clinical literature that adult children of alcoholics (ACOAs) are uniquely impacted by their parents' alcohol abuse, 25-35 year old daughters (N = 184) of alcohol-abusing, psychiatrically distressed, comorbid and normal parents were compared on measures of fear of intimacy, generalized psychological distress, perceived love inconsistency from parents and perceived interparental conflict. Neither fear of intimacy nor daughters' psychological distress differed across groups. Daughters of psychiatrically distressed and comorbid mothers recalled greater love inconsistency from mother than from father. Daughters of psychiatrically distressed and comorbid fathers recalled greater interparental conflict and daughters of comorbid fathers recalled greater love inconsistency from fathers than did daughters of alcoholic fathers. The proposed unique features of ACOA daughters and of the alcoholic family environment were not identified. The findings are discussed in terms of the clinical literature on ACOAs. PMID- 7990471 TI - The shifting importance of alcohol and marijuana as gateway substances among serious drug abusers. AB - Prior research based on representative samples drawn from the general population suggests persons tend to follow a common developmental pathway from use of alcohol as youths through possible use of marijuana as teens potentially leading to use of more serious substances as adults. Based on this model, alcohol and marijuana act as gateways, whereby persons who do not onset to alcohol rarely onset to marijuana; similarly, non-marijuana users rarely onset to more serious substance use and abuse. This study examines whether a sample of serious drug abusers recruited from New York City in 1988-89 followed the same developmental pathway as observed in general populations. The results suggest that alcohol is not a prerequisite for progression to marijuana, but marijuana use nearly always precedes use of more serious substances such as cocaine, crack and heroin. Furthermore, with the growing prevalence of marijuana (since 1965) the importance of alcohol as a gateway to marijuana use appears to have declined and marijuana's role as a gateway to serious drug use appears to have increased. PMID- 7990472 TI - Indexing cognitive tests to alcohol dosage and comparison to standardized field sobriety tests. AB - Cognitive tests from a computerized battery of mental tests and standardized roadside field sobriety tests (FST) were administered in three experiments involving graded dosages of alcohol but different administration schedules. In the first experiment, subjects were raised to one of four levels of alcohol dosage in four sessions 1 week apart. In the second experiment, the descending branch of the blood alcohol concentration (BAC) curve was monitored from 150 mg/dl BAC in a single session. In the third experiment, the ascending and descending limbs of the alcohol dosage curve were followed over a single session. Dose response relationships were observed for all tests, and the changes were statistically significant (p < .001) in all three studies for all tests when evaluated singly, except for grammatical reasoning. When cognitive and FST tests were combined into a single multiple regression analysis, Gaze Nystagmus consistently accounted for the most variance in BAC, followed by code substitution. While multiple regression analyses reveal that tests from the two batteries can be combined to improve overall prediction of alcohol concentration, it is also true that the two batteries share considerable variance (i.e., > 30%). This suggests that, while the two batteries may not be substitutable, they are measuring different aspects of the same thing. PMID- 7990474 TI - Stereotaxic breast biopsy--an emerging technology and new challenge for the surgical oncologist. PMID- 7990473 TI - The effects of cue exposure on reaction time in male alcoholics. AB - The present study investigates reaction time (RT) as a measure of attentional deficits produced during alcohol cue exposure. Twenty-four male alcoholic patients responded to a series of computer-generated tones as rapidly as possible during baseline and again during either an alcohol cue exposure period or exposure to a control beverage (water). Patients required increased time to respond to the tones when exposed to alcohol cues. No such increase in RT was found during exposure to a control beverage. In addition, RT was significantly correlated with self-reported urge to drink. These data provide initial validation for the use of RT as an objective measure of cue reactivity. Both theoretical and clinical implications for the use of RT as a measure of the effects of cue exposure are discussed. PMID- 7990475 TI - Chondrosarcoma of bone: oncologic and functional results. AB - A retrospective review of 27 patients (21 males and 6 females) with chondrosarcoma of bone was performed to evaluate the oncologic and functional results. The average age of the patients was 48 years (range: 17-76). The tumor sites were pelvis in 10 cases, distal femur in 2, proximal tibia in 3, rib in 2, and other in 10. One patient with Ollier's disease had chondrosarcoma at two different sites simultaneously. Surgical stages were I A in 8 cases, I B in 8, II A in 1, and II B in 10. Two patients had no surgical treatment. Amputation was performed in 5 cases and en bloc resection in 20. An uncontaminated radical or wide surgical margin was achieved in 13 of 25 cases. Additional surgery was performed in seven cases; for deep infection in one case and for local recurrence or metastasis in six. Local recurrence developed in seven patients (26%). At follow-up, four patients had died of disease (15%), one patient had died of another cause, and two patients were alive with disease (7%). No evidence of disease was found in 20 patients (74%). The oncologic results of limb salvage and amputation in chondrosarcoma of the limbs were good, although there was one failure of limb salvage, caused by infection. Due to surgical inaccessibility, results of the management of chondrosarcoma of the pelvis were poor. The average functional evaluation of 16 patients (average follow-up: 104 months) was 75% (range: 30-100). The Musculoskeletal Tumor Society ratings were excellent in four cases, good in seven, fair in four, and poor in one. PMID- 7990476 TI - Effects of preoperative chemotherapy on DNA ploidy patterns, cell cycle, and histological findings in gastric and colonic cancer patients. AB - The effects of preoperative chemotherapy on gastric and colonic cancers have yet to be evaluated fully. In this study, its effects were assessed by studying DNA ploidy patterns, cell cycles, and histological findings in such patients. Thirty nine patients with gastric or colonic cancer were given preoperative chemotherapy with UFT (an admixture of tegafur and uracil). Biopsy specimens for analysis were obtained before chemotherapy through a gastroscope or colonoscope and after chemotherapy from resected tumors. The DNA ploidy patterns and cell cycles were evaluated using a flow cytometer and the tissues were examined histologically. The DNA ploidy pattern was diploid (D) in 12 gastric and 13 colonic cancer patients and aneuploid (A) in 10 and 4 patients, respectively. After chemotherapy, the pattern changed in nine gastric (A-->D: 7, D-->A: 2) and six colonic cancer patients (A-->D: 3, D-->A: 3) and was unchanged in the remaining patients. Cell cyclic analysis showed decreased G1- and increased S-phase fractions in 10 of 12 patients with gastric and 6 of 10 patients with colonic cancer. Histologically, decreased tumor cellularity, increased fibrosis, and/or cytological changes were observed in both cancers after chemotherapy. Gastric and colonic cancers in which the DNA ploidy pattern changed from aneuploid to diploid, G1- decreased and S-phase increased, and/or histological changes were observed, were considered to have responded to preoperative UFT administration. PMID- 7990477 TI - Antitumor effect of neocarzinostatin conjugated to human/mouse chimeric Fab fragments of the monoclonal antibody A7 on human pancreatic carcinoma. AB - The anticancer agent neocarzinostatin (NCS) was bound covalently to human/mouse chimeric Fab fragments of the monoclonal antibody A7 to form the conjugate chA7Fab-NCS. The antitumor effect of chA7Fab-NCS was tested by measuring the inhibition of 3H-thymidine incorporation into human pancreatic carcinoma cells. The chA7Fab-NCS was approximately 2.3 times as effective as free NCS against human pancreatic carcinoma cells which reacted with the monoclonal antibody A7. The antitumor activity of chA7Fab-NCS was inhibited by excess chA7Fab. ChA7Fab NCS had an antitumor effect equivalent to free NCS on human pancreatic carcinoma cells which did not react with the monoclonal antibody A7. ChA7Fab-NCS appears to be a potentially useful conjugate for immunotargeting chemotherapy against pancreatic carcinoma. PMID- 7990478 TI - Practical management of post-thyroidectomy hematoma. AB - Thyroid diseases and surgery for thyroid neoplasms are both very common. Several complications of thyroidectomy are well known. Some of these are quite disturbing, such as recurrent laryngeal nerve injury and permanent hypoparathyroidism. However, postoperative hematoma often in the recovery room may be fatal. Close observation and early intervention are of utmost necessity in the post-thyroidectomy period. In a series of 600 thyroidectomies performed over a period of 11 years, eight patients developed postoperative hematoma. Seven of them underwent re-exploration, while one patient was treated conservatively. Two patients had second re-exploration for hematoma reaccumulation. All patients recovered very well after re-exploration except one elderly patient who required ventilatory support due to poor pulmonary reserve; after a week of ventilatory support and a tracheostomy, she too recovered well. One patient had the hematoma re-explored as late as 24 hours after the operation, while the remainder were re explored within 4-6 hours after the initial procedure. Because of the extent of edema of the larynx and pharyngeal wall, it is very important that a senior, experienced person perform intubation in these patients. It is also very important to recognize that when the patients lie down flat, they may develop acute airway distress; hence, one must be prepared to intubate them emergently. We recommend close recovery room observation after thyroidectomy and early exploration and evacuation of hematoma in all patients who develop postoperative hematoma. A conservative approach may be considered in selected patients with minimal hematoma and no progression. However, it generally takes a long time for the hematoma to resorb. A better understanding of the complications of thyroidectomy will minimize morbidity and make thyroidectomy a safer procedure and a surgical triumph. PMID- 7990479 TI - Adjuvant chemotherapy for resectable gastric cancer: a preliminary report. AB - In this prospectively random study, the effect of oral Ftorafur as an adjuvant chemotherapy was compared with that of oral placebo in patients with Stage II and Stage III gastric cancer. Patients had undergone a subtotal gastrectomy with a resection margin that should have been free of tumors. Ftorafur (10 mg/kg) was given daily to 59 Group A patients. Multiple vitamins were given twice a week to 56 Group B patients. We found that there was no statistical significance in Stage II patients with regard to survival. In Stage III patients, those treated with oral Ftorafur had better 3-year and 5-year survival rates than those receiving oral placebo. This preliminary report on this ongoing study seems to indicate that long-term postoperative Ftorafur treatment may be beneficial to Stage III gastric cancer patients. PMID- 7990480 TI - Giant cell tumor of bone: oncologic and functional results. AB - Giant cell tumor of bone is a challenging surgical problem due to its mostly aggressive growth with tendency to recur locally, to develop in rare instances pulmonary metastases without histologic evidence of malignant changes, and due to its potential to dedifferentiate into a frankly malignant tumor in a limited number of patients. It is treated in many different ways because of the difficulties in finding a type of treatment with the best functional results without compromising oncologic results. This paper describes 19 patients with giant cell tumor of bone. Following 19 procedures (including 6 intracapsular resections [curettage]) in 17 patients in our hospital only 2 recurrences (10.5%) occurred, both after curettage. Functional results after curettage without recurrence were favorable. Marginal or wide resections did not result in any recurrence, but were functionally inferior to curettage; an exception to the latter was the resection-arthrodesis of the distal radius in one patient. PMID- 7990481 TI - Thyroid cancer treated in Chang Gung Memorial Hospital (northern Taiwan) during the period 1979-1992: clinical presentation, pathological finding, analysis of prognostic variables, and results of treatment. AB - This study is a retrospective analysis of 248 thyroid cancer patients who received their primary treatment in the Chang Gung Memorial Hospital during the period January 1979 to December 1992. Among these cases, there were 173 papillary thyroid cancers (69.8%), 52 cases of follicular thyroid cancer (21%), 7 cases of medullary thyroid cancer (2.8%), and 16 cases of anaplastic thyroid cancer (6.5%). The subjects included 184 female patients with a mean age of 40.7 +/- 14.3 years and 64 males patients with a mean age of 49.2 +/- 14.3 years. Most of the cases had a nearly total thyroidectomy after the diagnosis was confirmed by frozen section during the operation. During the follow-up period, 19 (8.2%) patients diagnosed with well-differentiated thyroid cancer died of thyroid cancer in contrast to 12 patients (75%) with anaplastic thyroid cancer. The 1-year Greenwood survival probabilities after the disease is diagnosed in papillary, follicular, and anaplastic thyroid cancer are 0.98, 0.86, and 0.25, respectively. For the analysis of prognostic variables in well-differentiated thyroid cancer patients, 16 factors were entered for univariate and multivariate analysis. Using a log-rank univariate analysis, survival was significantly associated with the cell type of the primary tumor, age, clinical staging, postoperative 131I pattern, tumor size, postoperative thyroglobulin (Tg) level and postoperative x ray results. In the Cox multivariate regression analysis the combination factors that gave the best prognostic value were the association of x-ray finding (P = .004), age (P = .017), and Tg level (P = 0.19). In conclusion, thyroid cancer is not an unusual disease in Taiwan. As previously reported anaplastic thyroid cancer has a poor prognosis. In this limited period of follow-up study, the patients' age with postoperative first positive x-ray finding and Tg level may provide the prognostic factors for patients with well-differentiated thyroid cancer. PMID- 7990482 TI - Transscrotal approach to testicular tumors: an anatomical approach. AB - Performing a conventional radical inguinal orchiectomy for suspected testicular cancer has three important deficiencies: 1) A benign lesion can unnecessarily and unknowingly be treated by orchiectomy. 2) Alternate routes of tumor dissemination (superficial external pudendal veins) are not clamped or destroyed before the tumor-bearing testis is brought up through the external inguinal ring. 3) The act of squeezing the testis through the external inguinal ring may be an important cause of tumor spread. Presented in this paper is a transscrotal approach that eliminates these three deficiencies. It is advocated for critical clinical evaluation. PMID- 7990484 TI - Simple method to record breast lesion: the CNSD coding system. PMID- 7990483 TI - Techniques to simplify esophagogastric circular stapled anastomoses. AB - Stapling devices for end-to-end anastomoses (EEA) have facilitated more rapid and reliable reestablishment of esophagogastric continuity following esophageal resections. Despite their ease of use, various intraoperative problems can arise, especially with the esophageal pursestring or the insertion of the anvil into the fragile, commonly contracted lumen. This paper describes various technical details that are useful adjuncts to allow creation of rapid, consistently successful EEA stapled esophagogastric anastomoses. These techniques are of particular value in the resident teaching setting. PMID- 7990485 TI - Innovative technique for division of the dorsal tongue flap. PMID- 7990486 TI - Undifferentiated tumors: an immunohistochemical analysis on biopsies. AB - Immunohistochemical staining was performed on 145 biopsies with a diagnosis of undifferentiated or poorly differentiated tumor in order to classify them into lymphoid, epithelial, or mesenchymal in origin. It was possible to arrive at a histogenetic diagnosis on immunostaining in 85.5% of cases. Immunostaining confirmed the diagnosis in 32.4% and contributed to diagnosis in 53.1%. Malignant lymphoma was the most common diagnosis (35.9%), followed by carcinoma (23.4%). A panel of antibodies consisting of anti-common leucocyte antigen (LCA), anti epithelial membrane antigen (EMA), anti-cytokeratin (CK), anti-low to intermediate molecular weight cytokeratin (CAM 5.2), anti-S-100 protein (S-100), and anti-vimentin (VM) may resolve, to a large extent, some of the common diagnostic problems. PMID- 7990487 TI - Thymic carcinoma with glandular differentiation arising in a congenital thymic cyst. AB - A case of thymic carcinoma with glandular differentiation arising in congenital thymic cyst in a 50-year-old male is reported. Neoplasia in congenital thymic cyst is a rare phenomenon and is seldom associated with glandular differentiation. It is important to differentiate these neoplasms from carcinomas of the lower respiratory tract and from thymic carcinomas with secondary cystic degeneration, in view of their relatively good prognosis and the therapeutic implications. PMID- 7990488 TI - Some neuropharmacological effects of an ethanolic extract of Maprounea africana in rodents. AB - The ethanolic extract of the leaves of Maprounea africana (Euphorbiaceae), a medicinal plant in the Congolese traditional medicine, induced hypothermia and reduced the latency to the loss of the righting reflex and prolonged the sleeping time induced by pentobarbital in mice. It also significantly delayed the onset of clonic convulsions induced by pentylenetetrazole in mice. However, the extract did not affect either generalized convulsions induced by maximal electroshock and picrotoxin or limbic status epilepticus produced by pilocarpine and kainic acid. PMID- 7990489 TI - Hypoglycaemic effect of Artemisia herba alba. II. Effect of a valuable extract on some blood parameters in diabetic animals. AB - Artemisia herba alba is widely used in Iraqi folk medicine for the treatment of diabetes mellitus. However, very few scientific and medical studies were carried out to assess the efficacy and toxicity of A. herba alba. In this study feeding diabetic rats and rabbits with 0.39 g/kg body weight of the aqueous extract of the aerial parts of the plant for 2-4 weeks shows a significant reduction in blood glucose level, prevents elevation of glycosylated haemoglobin level and possesses a hypoliposis effect, in addition to the protection against body weight loss of diabetic animals. PMID- 7990491 TI - Effects of hydroalcoholic extracts of Portulaca pilosa and Achyrocline satureioides on urinary sodium and potassium excretion. AB - Porulaca pilosa has been used in Brazil as a traditional remedy to cause diuresis, antipyresis and analgesia. Achyrocline satureioides has been used in folk medicine as antiinflammatory, hypoglycemic, sedative and to treat gastrointestinal disorders such as diarrhea and dysentery suggesting that it may affect salt and water reabsorption by the gastrointestinal tract. In the current study, hydroalcoholic extracts of both plants were investigated in order to examine their renal effects. The results support the claim that extracts of P. pilosa present renal effects but not the popular belief that it affects diuresis. It has also been provided that, in rats, it causes an increase in K excretion without a concomitant change in water diuresis or Na excretion. Our findings also support the popular belief that A. satureioides does not apparently have renal effects and it might change renal ion transport based on observations that it affects gastrointestinal reabsorption. PMID- 7990490 TI - An antifungal compound from Solanum nigrescens. PMID- 7990492 TI - Antimicrobial activity of bark extracts of Bridelia ferruginea (Euphorbiaceae). AB - Water and ethanol extracts of Bridelia ferruginea were examined for phytochemical and antimicrobial properties. The extracts, which were tested at a final concentration of 5 mg/ml, produced in vitro antimicrobial activities in assays against hospital strains of Staphylococcus aureus, Candida albicans, Staphylococcus epidermidis, Escherichia coli, Streptococcus lactis, Proteus vulgaris, Proteus mirabilis, Streptococcus pyogenes and Klebsiella sp. The zones of inhibition produced by the extracts in agar diffusion assays against the test micro-organisms ranged from 4 to 20 mm, while the chloramphenicol antibiotic control produced zones that measured 15-36 mm. Preliminary phytochemical analysis of the plant extracts showed the presence of phenols and tannins. Sesquiterpenes, anthroquinones, and saponins were not detected in the extracts. The Gram-negative bacteria appeared to be more susceptible (4-20 mm) to the antimicrobial effect of the extracts than the Gram-positive organisms (4-18 mm). PMID- 7990493 TI - Syosaiko-to and saiboku-to (Chinese-Japanese herbal medicine) suppress the release of arachidonic acid metabolites from cultured porcine pulmonary artery endothelial cells. AB - The influences of Syosaiko-to and Saiboku-to, traditional Chinese-Japanese medicines, on the arachidonic acid metabolism of porcine pulmonary artery endothelial cells (PPAEC) in culture were investigated. 6-keto-PGF1 alpha, a stable end product of prostacyclin, released by PPAEC during a 48 h incubation period with 1000 micrograms/ml of Syosaiko-to or Saiboku-to was significantly decreased. Analysis of the eicosanoid profile by high performance liquid chromatography revealed that both cyclooxygenase and lipoxygenase derivatives were released in smaller than usual proportions from PPAEC during 24 h incubation periods with 500 micrograms/ml of Syosaiko-to or Saiboku-to. Clinically, Syosaiko to is used for chronic hepatitis and Saiboku-to is prescribed for bronchial asthma. The experimental findings could explain the anti-inflammatory effect of Syosaiko-to and Saiboku-to from the perspective of their influences on arachidonic acid metabolic activity associated with PPAEC. PMID- 7990495 TI - Effect of crude extract of roots of Bredemeyera floribunda Willd. II. Effect on glomerular filtration rate and renal tubular function of rats. AB - The effect of crude extract of roots of Bredemeyera floribunda Willd., Polygalaceae used by Brazilian popular medicine as a potent diuretic, on renal function in antidiuresis or water diuresis in rats, was studied. During intravenous infusion of the extract (0.05 mg/min/100 g), mean arterial pressure did not change significantly but urine flow, glomerular filtration rate, fractional water and sodium excretion and solute clearance increased significantly, in both groups of animals. In antidiuresis rats the extract significantly increased reabsorption of water by the collecting duct and in water diuresis animals the extract significantly increased free water clearance. Our findings indicate a direct effect of extract on glomerular filtration rate, possibly by detergent like interactions with structural components of glomerular membranes and/or by decreasing renal perfusion pressure. The study on the concentrating and diluting mechanisms suggests preferential action of extract in the proximal tubular cells, possibly on the (Na(+)-K+)-ATPase countertransport system and/or on other proteins components of tubular cell membranes involved with salt transport mechanisms. PMID- 7990494 TI - Effect of crude extract of roots of Bredemeyera floribunda Willd. I. Effect on arterial blood pressure and renal excretion in the rat. AB - The infusion of the dried roots of Bredemeyera floribunda Willd. is used in Brazilian popular medicine as a potent diuretic, especially in the treatment of hypertension and nephrolithiasis (renal calculi). Intravenous administration of crude root-extract (20-80 mg/kg) to anesthetized rats induces clear dose dependent and reversible hypotensive responses. At higher doses the extract leads to bradycardia and death. In doses that do not alter the arterial blood pressure, the extract elicited immediate and dose-dependent reversible increase of water, sodium, and potassium renal excretion. The results, apart from indicating that the renal effect of the extract is not due to its systemic hypotensive action, support the folk therapeutic use of the infusion of the root-extract as a diuretic. PMID- 7990496 TI - Effect of crude extract of roots of Bredemeyera floribunda Willd. III. Effect on hormone-stimulated water transport in isolated frog skin. AB - The diuretic activity of the crude extract of roots of Bredemeyera floribunda Willd. (Polygalaceae) was investigated on basal and hormone-stimulated absorptive water transport in the isolated frog skin. The extract, added to the mucosal skin surface, at the peak of oxytocin (Oxy) action induces steady and dose-dependent reduction of water transport. Pre-treatment of the skins during 2 h with the extract, added to mucosal skin surface, renders the epithelium non-responsive to oxytocin. These effects are not observed when the extract is added to the serosal skin surface. Basal water transport is not altered by the extract. The results, apart from indicating inhibition of the oxytocin-stimulated water transport in frog skin epithelium, support the folk therapeutic use of infusion of the root extract as a diuretic. PMID- 7990497 TI - Hyperglycemic and insulin release inhibitory effects of Rosmarinus officinalis. AB - The effects of the volatile oil extracted from the leaves of Rosmarinus officinalis on glucose and insulin levels were investigated in normal rabbits, after the administration of an intraperitoneal glucose tolerance test (GTT). Also, the effects of the volatile oil on fasting plasma glucose levels, were studied in alloxan diabetic rabbits. In normal rabbits, the intramuscular (i.m.) administration of the volatile oil (25 mg/kg) produced 20% (P < 0.05), 27% (P < 0.01) and 55% (P < 0.001) increases in plasma glucose levels, above those of control animals, at the 60, 90 and 120 min intervals, respectively, following the administration of the intraperitoneal (i.p.) glucose test. The same treatment also resulted in a 30% (P < 0.002) decrease in serum insulin level, in comparison with that of control rabbits at the 30 min interval. In alloxan diabetic rabbits, R. officinalis volatile oil increased fasting plasma glucose levels by 17% (P < 0.05) above those of untreated animals 6 h after its administration. These data suggest that the volatile oil of R. officinalis has hyperglycemic and insulin release inhibitory effects in the rabbit. PMID- 7990498 TI - The ethnopharmacology and phytochemistry of Eremophila species (Myoporaceae). PMID- 7990499 TI - Solanaceae as medicinal plants in Israel. AB - In a recent survey, 106 local healers in Israel were interviewed concerning the use of Solanaceae as medicinal plants. The main findings reveal that: (a) only four species (Lycium europeaum, Solanum nigrum, Hyoscyamus aureus, Hyoscyamus albus) are extensively used today; (b) the use of some traditional plants has been almost abandoned (Datura spp., Mandragora autumnalis, Withania somnifera); (c) today all the plants are applied externally, they are rarely used as narcotics; (d) most use of these plants is local, only in a few cases is a uniform use found throughout the whole country, and in all ethnic groups; (e) the extensive distribution of modern, safe narcotics, sedatives and anaesthetics has reduced the use of the Solanaceae for these purposes. PMID- 7990500 TI - Extracts and fractions of Thymus capitatus exhibit antimicrobial activities. AB - Preliminary phytochemical screening of the plant Thymus capitatus exhibited the presence of saponins, resins, flavonoids, essential and fixed oils. Aqueous and ethanolic extracts (10-200 mg/ml) as well as saponin, resin and essential oil of the plant (10-5000 micrograms/ml inhibited the growth of several bacteria and fungi. PMID- 7990501 TI - Antitumor and cytotoxic screen of 5,6,7-trisubstituted flavones from Gomphrena martiana. AB - An in vivo antitumor screening of extracts of Gomphrena martiana indicated positive activity in the petroleum ether extract, and its further bioactivity directed fractionation resulted in a lipophilic flavonoid fraction. Upon inoculation of various doses of 5,6,7-trisubstituted flavones on two murine tumor lines, Sarcoma 180 and Ehrlich's carcinoma, a decrease of tumor growth was observed. An in vitro KB cultured cell screen indicated cytotoxicity. PMID- 7990502 TI - Antibacterial activity of plant extracts used externally in traditional medicine. AB - Plants of 28 families, selected on the basis of medicinal folklore reports and literature data, were studied in a screening program. Aqueous extracts of plants used externally for the treatment of infected skin lesions were tested for their antibacterial potential. The results indicated that about 60% of the plant extracts tested exhibited some level of antibacterial action. PMID- 7990503 TI - In vitro antibacterial activity of Argentine folk medicinal plants against Salmonella typhi. AB - Boiling water extracts of 132 samples from 54 plant families, commonly used in Argentine folk medicine, were screened for antibacterial activity against Salmonella typhi. The agar-well diffusion method was used. A reference concentration-response curve for ampicillin was used to estimate the apparent activity of the samples. Twenty four species showed antibacterial activity. Cassia occidentalis roots, Heimia salicifolia aerial parts, Punica granatum fruit pericarp and Rosa borboniana flowers produced some of the more active extracts. Taking into account the multiple resistance of Salmonella typhi, these findings could be useful in the search for new clinically useful antimicrobials. PMID- 7990504 TI - Isolation of pharmacologically active benzodiazepine receptor ligands from Tilia tomentosa (Tiliaceae). AB - Tilia species are traditional medicinal plants widely used in Latin America as sedatives and tranquilizers. For this purpose, the infusion of their inflorescences is used to prepare a tea. In this study extracts of inflorescences from Tilia tomentosa Moench, one of the species found in the market, were purified using a benzodiazepine (BZD) binding assay to detect BZD receptor ligands in the different fractions. One of the ligands was identified as kaempferol, but it had low affinity (Ki = 93 microM) for this receptor, and did not produce sedative or anxiolytic effects in mice. On the other hand, a complex fraction, containing as yet unidentified constituents, but probably of a flavonoid nature, when administered intraperitoneally in mice, had a clear anxiolytic effect in both the elevated plus-maze and holeboard tests, two well validated pharmacological tests to measure anxiolytic and sedative compounds. This active fraction had no effect on total and ambulatory locomotor activity. In conclusion, our results demonstrate the occurrence of active principle(s) in, at least, one species of Tilia that may explain its ethnopharmacological use as an anxiolytic. PMID- 7990506 TI - Measuring complex admittance and receptor current by single electrode voltage clamp. AB - Studying the membrane properties of small excitable cells like sensory receptors in situ is often difficult. Two new techniques are described here which utilize white noise during single-electrode voltage-clamp. Cells are impaled with a single microelectrode and voltage-clamped to a given holding potential, using a time-sharing technique. The first method, based on modulating the voltage command with repeated sequences of a pseudorandom stimuli, allows measurements of cell conductance (complex admittance) in the frequency domain. The second method is designed to characterize the dynamics of the receptor current in the frequency domain. In both cases, R1-6 type blowfly photoreceptors were used as experimental models. The photoreceptor was first light-adapted to a steady light background and then clamped to the resulting potential. A pseudorandomly modulated light stimulus was then superimposed on the steady light background and the resulting receptor current was recorded. The frequency response was then calculated from the light modulation and the receptor current via fast Fourier transform (FFT). By using intracellularly applied ion channel blockers, the effects of active and passive membrane properties in modulating the transmitted signals could also be studied. PMID- 7990505 TI - Augmentation of murine natural killer cell and antibody dependent cellular cytotoxicity activities by Phyllanthus emblica, a new immunomodulator. AB - When administered orally, Phyllanthus emblica, an excellent source of vitamin C (ascorbate), has been found to enhance natural killer (NK) cell activity and antibody dependent cellular cytotoxicity (ADCC) in syngeneic BALB/c mice, bearing Dalton's lymphoma ascites (DLA) tumor. P. emblica elicited a 2-fold increase in splenic NK cell activity on day 3 post tumor inoculation. Enhanced activity was highly significant on days 3, 5, 7 and 9 after tumor inoculation with respect to the untreated tumor bearing control. A significant enhancement in ADCC was documented on days 3, 7, 9, 11 and 13 in drug treated mice as compared to the control. An increase in life span (ILS) of 35% was recorded in tumor bearing mice treated with P. emblica. This increased survival was completely abrogated when NK cell and killer (K) cell activities were depleted either by cyclophosphamide or anti-asialo-GM1 antibody treatment. These results indicate: (a) an absolute requirement for a functional NK cell or K cell population in order that P. emblica can exert its effect on tumor bearing animals, and (b) the antitumor activity of P. emblica is mediated primarily through the ability of the drug to augment natural cell mediated cytotoxicity. PMID- 7990507 TI - Simultaneous multisite recordings and stimulation of single isolated leech neurons using planar extracellular electrode arrays. AB - Planar extracellular electrode arrays provide a non-toxic, non-invasive method of making long-term, multisite recordings with moderately high spatial frequency (recording sites per unit area). This paper reports advances in the use of this approach to record from and stimulate single identified leech neurons in vitro. A modified enzyme treatment allowed identified neurons to be extracted with very long processes. Multisite extracellular recordings from the processes of such isolated neurons revealed both the velocity and direction of action potential propagation. Propagation in two cell types examined was from the broken stump towards the cell body (antidromic). This was true for spontaneous action potentials, action potentials produced by injecting current into the cell body and extracellular stimulation of the extracted process via a planar extracellular electrode. These results extend previous findings which have shown that the tip of the broken stump of extracted neurons has a high density of voltage-activated sodium channels. Moreover they demonstrate the applicability of extracellular electrode arrays for recording the electrical excitability of single cells. PMID- 7990509 TI - Design CAD-3D: a useful tool for 3-dimensional reconstructions in biology. PMID- 7990508 TI - Image analysis of neuritic regeneration by adult rat dorsal root ganglion neurons in culture: quantification of the neurotoxicity of anticancer agents and of its prevention by nerve growth factor or basic fibroblast growth factor but not brain derived neurotrophic factor or neurotrophin-3. AB - Peripheral neuropathies are a common side effect of chemotherapeutic agents, particularly antineoplastic drugs such as taxol, cisplatin, or vinca-alkaloids (vincristine, vinblastine, vindesine). Using dissociated cultures of adult rat dorsal root ganglion (DRG) neurons and video image analysis after neurofilament immunostaining, we have designed a system that allows: (i) rapid screening of potential neurotoxic agents, with the establishment of dose-response curves and the calculation of IC50; (ii) quantification of neurotrophic effects; and (iii) demonstration of neuroprotection by trophic factors. In particular, we show that nerve growth factor (NGF) and basic fibroblast growth factor (bFGF) stimulate in vitro neuritic regeneration by adult rat DRG neurons, while brain-derived neurotrophic factor and neurotrophin-3 lack such effects. Furthermore, 24 h of pretreatment by NGF or bFGF drastically decreases the neurotoxic effect of vincristine and cisplatin. PMID- 7990510 TI - A simplified method for the measurement of caffeine in plasma and brain: evidence for a cortical-subcortical caffeine concentration differential in brain. AB - We describe a much simplified high-performance liquid chromatography (HPLC) method for the measurement of caffeine in plasma and brain. A particularly attractive feature of this method is that a simple methanol/water (60:40) mobile phase can be used both for plasma and brain samples. In addition, the method is compatible with solid-phase extraction for plasma samples and conventional brain tissue preparation for biogenic amine analysis with HPLC. Using this method to measure the concentrations of caffeine in plasma and brain of rats which received 10 or 50 mg/kg caffeine injections, we found substantial concentration differences between cortical and subcortical brain tissue. Specifically, at the 10 mg/kg dose, a nearly 2-fold difference between cortex and striatum caffeine concentrations was observed. A shortcoming of many neurobehavioral studies of caffeine effects is the absence of caffeine concentration measurements. The simplicity of the present method for the measurement of caffeine in plasma and brain tissue makes it a practical and feasible procedure to incorporate into neurobehavioral studies designed to elucidate the CNS actions of caffeine. PMID- 7990511 TI - A new method to quantify behavioral attention to a stimulus object in a modified open-field. AB - A new method was developed to measure locomotion and attention to a stimulus object in a typical open-field environment using a video image-analyzer system. A computer-generated central zone (CZ) composing 1/9 of the open-field floor area was monitored independently from the rest of the area. Intermittently, a 4 x 4 x 2 cm object was placed in the CZ. In 10 min test sessions, the presence of the object repeatedly and consistently increased the animal's time spent in the CZ as compared with tests when the object was absent. The presence of the object, however, did not increase either the number of entries to the CZ or overall locomotor activity. The object reliably elicited an investigatory response when the animal enter the CZ but otherwise was behaviorally neutral. Thus, by incorporating a stimulus object in a conventional open-field test environment, the present methodology extends the open-field test beyond the measurement of overall spontaneous activity to include an assessment of behavioral processes linked to attention mechanisms. PMID- 7990512 TI - The measurement of tremor using simple laser systems. AB - Quantification of movement pathologies is an important challenge of the clinical and research laboratories today. Basically, two problems must be addressed. The first one is to find the appropriate technology; the second is to develop adequate measures from the raw data which will best discriminate between health and pathology. In this paper, we propose a simple method to record and analyse tremor and other microdisplacements of the upper extremities based on the recording of position by laser analog sensors. Any microcomputer equipped to perform analog-digital conversion is compatible for use with this system. The performance of the laser system is examined and compared with the performance of accelerometers. Finally, data recorded with a laser analog sensor from a patient with Parkinson's disease and a control subject are presented. This new laser based quantitative method may prove to be an important tool in early and differential diagnosis of neurodegenerative diseases of the central nervous system. PMID- 7990513 TI - Quantitative assessment of tactile allodynia in the rat paw. AB - We applied and validated a quantitative allodynia assessment technique, using a recently developed rat surgical neuropathy model wherein nocifensive behaviors are evoked by light touch to the paw. Employing von Frey hairs from 0.41 to 15.1 g, we first characterized the percent response at each stimulus intensity. A smooth log-linear relationship was observed, with a median 50% threshold at 1.97 g (95% confidence limits, 1.12-3.57 g). Subsequently, we applied a paradigm using stimulus oscillation around the response threshold, which allowed more rapid, efficient measurements. Median 50% threshold by this up-down method was 2.4 g (1.81-2.76). Correlation coefficient between the two methods was 0.91. In neuropathic rats, good intra- and inter-observer reproducibility was found for the up-down paradigm; some variability was seen in normal rats, attributable to extensive testing. Thresholds in a sizable group of neuropathic rats showed insignificant variability over 20 days. After 50 days, 61% still met strict neuropathy criteria, using survival analysis. Threshold measurement using the up down paradigm, in combination with the neuropathic pain model, represents a powerful tool for analyzing the effects of manipulations of the neuropathic pain state. PMID- 7990514 TI - Difference in extracellular cocaine concentration between the ventral tegmental area and the medial prefrontal cortex following intravenous administration as revealed by quantitative microdialysis coupled with in vivo calibration. AB - Two microdialysis probes (active length: 1 mm) were simultaneously lowered into the ventral tegmental area (VTA) and the medial prefrontal cortex (mPFC) of each male, adult Sprague-Dawley rat, anesthetized with chloral hydrate, to evaluate whether cocaine distribution between these two areas is uniform after i.v. injection of 3 mg/kg cocaine. Using a modified in vivo calibration method, we can estimate the extracellular cocaine concentration in those nuclei. This proposed calibration method offers the advantages of simplicity and speed. Measurement of the cocaine concentration in the dialysate and estimation of the extracellular cocaine concentration showed that extracellular cocaine in the VTA was significantly higher than that in the mPFC. Next, the active length of the dialysis probe was extended to 4 mm in order to examine the effect of the active probe length on the cocaine distribution profile between the mPFC and a mixed area of VTA and red nucleus. Surprisingly, the cocaine concentration in dialysate had a contradictory result compared to the extracellular cocaine concentration due to in vivo recovery in the mPFC (25.3 +/- 3.1%) which was significantly higher than that in the mixed area (17.5 +/- 1.6%). Firstly, these results suggest that distribution of cocaine following systemic administration was not uniform in the rat brain. Secondly, in a valid comparison of drug concentrations between the two dialysis areas, we must consider the in vivo recovery for each brain region. PMID- 7990515 TI - A new method to assess Pavlovian conditioning of psychostimulant drug effects. AB - Experimental studies of psychoactive drugs by pavlovian drug-conditioning methods, which originally began with investigations of drug-induced responses mediated by the autonomic nervous system, have now been expanded to include drug induced response effects expressed as modulations of spontaneous motoric behaviors. In the latter application, however, equivalent behavioral response outcomes in post-treatment tests for conditioning can occur following a psychostimulant drug treatment either through drug interference effects on habituation processes, drug-induced stress effects and/or by pavlovian conditioning of the drug-induced motoric activation effect. Current methodologies for the study of pavlovian conditioned drug effects and/or drug sensitization cannot distinguish among these possibilities. This methodological inadequacy was addressed by a modification of the conventional paired-unpaired treatment protocol. In the new protocol, the animal is sequentially placed into two test compartments with the drug treatment administered in conjunction with placement into the second test compartment. This design permits a differentiation of a pavlovian conditioned drug responses from non-conditioned drug effects through continuous measurement of the non-drug behavioral baseline in both the drug and non-drug control treatment groups combined with multiple response measurements and post-treatment tests for conditioning at variable post-conditioning intervals. The present study details the use of the new modified pavlovian protocol with repeated cocaine (10 mg/kg) treatment. A cocaine conditioned response at 1, 7, and 21 days post-conditioning was identified and distinguished from habituation and stress effects. PMID- 7990516 TI - A simplified method for manufacturing glass-insulated metal microelectrodes. AB - A simplified method to manufacture durable, glass-insulated, tungsten microelectrodes with sufficient control of the final electrode impedance is described. This method requires only two instruments, an electrolytic etcher for wires and pipette puller, for manufacturing these electrodes. The manufacture of these electrodes involves 3 steps: (1) etching tungsten wire to sharpen the tip, (2) insulating the electrode by pulling a glass pipette over the sharpened tungsten wire and (3) assessing and adjusting the tip exposure and impedance of the electrode to meet recording requirements. Control over the electrode impedance is easily accomplished by varying the distance between the uppermost portion of the heating coil and the sharpened wire tip before a glass pipette is pulled over the wire tip. This distance determines the area of tip exposure and also the location where the glass insulation ends and the exposed electrode tip begins. A performance test of these electrodes in a chronically prepared monkey showed that they were strong enough to repeatedly penetrate thickened dura mater without significant changes in impedance and to isolate cortical neuronal activity after these multiple penetrations. Furthermore, the strength of these microelectrodes eliminated the need to remove reactive granular tissue from the dura overlying the recording site. PMID- 7990517 TI - Brain fixation for acetylcholine measurements. AB - Brain fixation using a commercially available microwave oven (power output: 750 W) has been investigated as a means for enzyme inactivation preventing post mortem changes in brain acetylcholine (ACh) and choline (Ch) levels. Rats and mice were decapitated, and the severed heads immediately irradiated for 5.5 and 3 s, respectively, resulting in a complete inactivation of brain acetylcholine esterase (AChE) and choline acetyltransferase (ChAT). The ACh and Ch contents measured in various brain regions of rat and mouse were: (in rat) striatum 60.5 and 32.4 nmol/g, hippocampus 20.4 and 30.9 nmol/g, cortex 24.2 and 19.6 nmol/g; (in mouse) striatum 70 and 47.2 nmol/g, hippocampus 22. 1 and 30.2 nmol/g, cortex 22.9 and 27.9 nmol/g. These values were found in accordance with those reported in the literature by irradiating whole animals in instruments of higher power capabilities. Thus, the procedure described in the present work may be a simple and valuable means of brain fixation for neurochemical studies of brain ACh in small animal species. PMID- 7990518 TI - Intracellular dye injection of previously immunolabeled insect neurons in fixed brain slices. AB - Our method combines intracellular dye injection and immunohistochemistry. Under optical control, Lucifer Yellow was injected into immunohistochemically identified neurons that reside in fixed tissue. The technique allows visualization of the complete arborization patterns of immunostained neurons. Injections were performed on small neurons (somata < 10 microns in diameter). The technique works on microslices of insect brain. Standard immunohistochemical procedures have only been varied slightly, omitting Triton X-100 treatment. Anti Lucifer Yellow immunohistochemistry, or alternatively the photoconversion technique, enables extension of the morphological analysis of these cells to the electron microscopic level. In the present study, Lucifer Yellow injections were performed on immunohistochemically pretreated brain microslices (anti-Locusta tachykinin II antiserum) of the beetle Tenebrio molitor. PMID- 7990519 TI - Tension transduction device for functional evaluation of the rat peroneal nerve. AB - Current techniques for evaluating animal model nerve regeneration lack accurate, sensitive and reproducible methods to determine neuromuscular function. We have developed a tension transduction apparatus which measures the magnitude of ankle dorsiflexion produced by normal rats during bipolar stimulation of the surgically exposed peroneal nerve. Three groups of animals were used to evaluate the consistency and overall reliability of this apparatus. Within the first group of 4 animals, we determined variability in a single testing period of 8 successive stimulations. The mean normalized standard deviation of dorsiflexion tension produced was 2.9% of the mean. In the second group, comparison of right and left dorsiflexion tension in 8 animals showed a difference of less than 2% (right: 134.2 g; left: 131.6 g), demonstrating that one lower limb can be used as a control for the contralateral limb. In the third group, 12 animals were tested on two separate occasions, 2 months apart, tension production increased 10% (from 122 to 134 g) and corresponded with an average weight increase, per animal, of 100 g (30%) during the 2-month rest period. Despite the increase in weight and strength, the initial procedure had a negative effect upon the maximum tension produced compared to a previously unoperated leg (prior operation: 134 g; no prior operation: 144 g). The reproducibility of data obtainable with this new device allows for its incorporation in future studies, as well as the correlation of such functional data with other current methods of studying nerve regeneration. PMID- 7990520 TI - [Analysis of the DNA of the hepatitis B virus (HBV) in the serum and mononuclear cells of the peripheral blood in subjects with chronic infection by the HBV]. AB - BACKGROUND: Viral replication is one of the determining factors of the natural history of infection by the hepatitis B virus (HBV). The clinical significance of the viremia and the DNA-HBV findings in mononuclear cells was therefore analyzed. METHODS: The epidemiologic history, liver function tests and the Knodell index were analyzed in 117 patients with chronic hepatitis B (CHB) and 33 healthy HBV carriers. The DNA-HBV was studied in serum and mononuclear cells by dot-blot and polymerase chain reaction (PCR). RESULTS: The DNA-HBV was detected by dot-blot in 62/117 subjects with and in CHB 3/33 healthy carriers. Viremis was determined by PCR in 107/117 patients with CHB and in 22/23 healthy carriers. Both aspartate aminotransferase (AST) as well as alanine aminotransferase (ALT) and the Knodell index were greater in the patients with positive DNA-HBV dot-blot. No significant differences were observed in the liver function tests and Knodell index with regard to the viremia detectable exclusively by PCR. In the mononuclear cells of peripheral blood, DNA-HBV was observed in 62% by dot-blot and in 95% by PCR. The presence of DNA-HBV by dot-blot in these cells was associated to greater disease activity. CONCLUSIONS: The activity of chronic hepatitis B was correlated with the presence of high viremic levels with no direct relation being observed between low grade viremia and disease aggressivity. The finding of DNA-HBV by dot blot in mononuclear cells was associated with a greater activity of chronic hepatitis B, with these results being in agreement with the serologic data reported. PMID- 7990522 TI - [Immunity against tetanus in adults over the age of 49 years]. AB - BACKGROUND: Despite the existence of an effective, cheap vaccine with few side effects, tetanus remains present in Spain with most of the cases being observed in subjects over the age of 49 years. The present seroepidemiologic study was performed to detect the degree of protection of this population. METHODS: The presence of antitetanic antibodies were determined in 324 subjects over the age of 49 (range: 50-88 years, mean 65.5 +/- 9.8 years) in Guipuzcoa. A passive hemagglutination technique (Tetan test; Istituto Sieroterapico Milanese) was used to detect tetanic antitoxoid antibodies following validation of the technique with a neutralizing test of the toxin in white mouse. RESULTS: Only 12.3% (40/324) of the subjects were considered as immune versus tetanus. The older subjects were the least protected: 7.7% (8/104) of those over 70 years of age versus 17.3% (17/98) of those from 50-59 years of age (chi 2 = 4.34, p = 0.037). The women were globally less protected: 5.4% versus 17% (33/194) males (chi 2 = 9.72; p = 0.002). CONCLUSIONS: Most of the adult population over the age of 49 years in Guipuzcoa is not protected against tetanus. This is in contrast with the situation observed in the infant and adolescent population. Specific preventive measures directed at the adult and elderly population should be undertaken. PMID- 7990521 TI - [HIV infection declines among intravenous drug addicts in Barcelona: 1987-1993]. AB - BACKGROUND: The evolution of the prevalence of HIV infection in intravenous drug addicts who initiate hospital detoxication was analyzed. METHODS: Six hundred fifty intravenous drug addicts (535 males, 115 females) were analyzed for HIV and surveyed in regard to demographic variables and the use of drugs over a period of 7 years (1987-1993): age, sex, year of initiation of intravenous drug addiction, length of the habit and year of admission. RESULTS: Most of the subjects were men (82%) with a mean age of 19.7 years at the time of initiation to the use of i.v. drugs and an age of 25.9 years on admission to the unit. The mean time of i.v. drug addiction at admission was 74 months. The characteristics of the patients according to the year of admission were homogeneous in regard to age, length of drug addiction and male/female ratio. More than 50% of the subjects had initiated the use of i.v. drugs during the first half of the last decade. The global prevalence of HIV infection was of 66.3% with no differences being observed between sexes. The frequency of infection was shown to have globally decreased from 1987 to 1993 (p = 0.06) although the rates of HIV infection in women did not significantly modify (p = 0.08) in contrast to that of men (p = 0.05). CONCLUSIONS: The epidemia of HIV infection in intravenous drug addicts may have entered into remission following a decade characterized by a spread in the use of heroin and great diffusion of the disease. PMID- 7990523 TI - [Infection by Candida and granulocytopenia]. PMID- 7990524 TI - [Educative structure and quality in the training of medical specialties]. PMID- 7990525 TI - [Sepsis by Candida tropicalis in patients with granulocytopenia. A study of 10 cases]. AB - The aim of the present study was to analyze the main clinical and evolutive characteristics of a series of 10 patients diagnosed with sepsis by Candida tropicalis over a 5-year period in a Hematology Unit. The mean age of the 10 patients was 23 years (range 13-66 years) with 6 males and 4 females. Eight patients had acute leukemia, 1 non-Hodgkin's lymphoma and another patient had severe bone marrow aplasia. All the patients presented intense granulocytopenia (< 0.5 x 10(9)/L), had intravenous catheters and were receiving wide spectrum antibiotics as treatment for bacterial infection. The diagnosis of the fungal infection was based on the growth of C. tropicalis in blood cultures together with the evidence of tissue involvement by the fungus. Fever (> 38 degrees C) was the initial symptom of the infection in all the patients, being accompanied by myalgia in 5 cases, pleuritic pain in 2 and septic shock in 1. Violaceous erthymatomous pustules disseminated over the trunk and limbs, the histologic study of which demonstrated the presence of C. tropicalis were observed in 9 patients. Septic metastasis were found in the liver (2 cases), serosae (2 cases), the psoas muscle and the brain (1 case), respectively. Eight patients underwent treatment with amphotericin B which was complemented with 5-fluorocytosin in 6, with death occurring in the remaining 2 patients prior to the start of treatment. Three patients died with active fungal infection (2 by cerebral hemorrhage and 1 by septic shock). In 2 patients the infection evolved to chronic systemic candidiasis and in the remaining 5 patients infection was resolved with hemoperipheral values returning to normal. Sepsis by Candida tropicalis is a severe complication in patients with granulocytopenia, being mainly characterized by fever, cutaneous papulae and, to a lesser extent, muscle pain. Amphotericin B alone, or in combination with 5-fluorocytosin constitute a treatment of choice in this infection, which nonetheless is associated with an undisdainful mortality. PMID- 7990526 TI - [Mobility of medical students. Management model at the University of Oviedo, Spain]. PMID- 7990527 TI - [Recombinant factor VIII. An introduction to recombinant DNA technology and the first results published in the replacement treatment of hemophilia A]. PMID- 7990528 TI - [The costs of home hospitalization]. PMID- 7990529 TI - [The costs of home hospitalization]. PMID- 7990530 TI - [Sexual transmission of the hepatitis C virus]. PMID- 7990531 TI - [Caution in making conclusions in clinical investigation]. PMID- 7990532 TI - [Drugs and economics in my perspective. I: Uncritical attitude of physicians is the cause of costs]. PMID- 7990533 TI - [Risks and advantages of early discharge from maternity wards]. PMID- 7990535 TI - [Children of alcoholic mothers. Can we reach them via the services given to the abusers?]. PMID- 7990534 TI - [The Ottawa method. A good attempt to reduce the number of emergency x-ray examinations of feet and ankle joints]. PMID- 7990536 TI - [A study of remoxipride dosage and plasma concentration. New psychopharmaceuticals should be followed-up more strictly]. PMID- 7990537 TI - [Ambulatory treatment without complications. A 1-year experience in distal deep vein thrombosis]. PMID- 7990538 TI - [What is the connection between Parkinson disease and tardive dyskinesia?]. PMID- 7990539 TI - [A working group on colorectal cancer. No new system for staging is necessary]. PMID- 7990540 TI - [An ear-lobe crease as a predictor of coronary disease?]. PMID- 7990541 TI - [Hip fractures. The ADL capacity predicts the length of stay]. PMID- 7990542 TI - [Prediction of violence. Specify the context, population and time perspective for a more precise prediction of violence in mental patients]. PMID- 7990543 TI - [Implantation of synthetic hair is not risk-free]. PMID- 7990544 TI - [Pediatrics at a district level in Zimbabwe. Malnutrition and AIDS are the children's greatest threats]. PMID- 7990545 TI - [Gerhard Armauer Hansen. The discoverer of Mycobacterium leprae]. PMID- 7990546 TI - [Pharmacoepidemiological registry studies. Personal integrity and the EEC legislation]. PMID- 7990547 TI - [Use of a drug registry. Can asthma be aggravated by tretinoin?]. PMID- 7990549 TI - [New York rejects a proposal on physician-assisted suicide]. PMID- 7990548 TI - [Cosmetic psychopharmacology. Prozac--an American happy pill and a gold mine]. PMID- 7990550 TI - [An early test for all elite athletes]. PMID- 7990551 TI - [Diabetes and driving licence. More liberal regulations and certification are required]. PMID- 7990552 TI - [A crisis intervention team for hospital personnel. "Visiting activities" with psychological support in incidents of severe violence]. PMID- 7990553 TI - [Violence against personnel and patients. Increased violence among psychiatric patients]. PMID- 7990555 TI - [Wife/husband as kidney donors. Excellent results in spite of unrelated tissue]. PMID- 7990554 TI - [ACE inhibitors in heart failure. Increased safety in a cardiology clinic]. PMID- 7990556 TI - [Treatment of intestinal infections. Infectious diarrhea is frequent also in developed countries]. PMID- 7990557 TI - [From empiricism to scientific safety in false croup. Good documentation for corticosteroids]. PMID- 7990558 TI - [Quinolones may be used in the treatment of children. Exaggerated fear of adverse effects]. PMID- 7990559 TI - ["Brushing" in esophageal and cardiac lesions. A complement to conventional diagnostic methods]. PMID- 7990560 TI - [The man behind the syndrome: Julius Thomsen. He himself suffered of a type of myotonia]. PMID- 7990561 TI - [The myotonia diseases--a minireview]. PMID- 7990562 TI - [Is possession of a drivers licence of patients with insulin-treated diabetes a risk? Varying medical practice behind insufficient control]. PMID- 7990563 TI - [How can we assess a case of appendicitis?]. PMID- 7990564 TI - [Clinical diagnosis when it is at its best!]. PMID- 7990565 TI - [The MEDGER document. A new document for cooperation between internal medicine and geriatrics]. PMID- 7990566 TI - [Violence and threats in health care: every third physician exposed to physical violence by patients]. PMID- 7990567 TI - [Care of mentally disturbed criminals. The county administrative court decides- not the physician]. PMID- 7990568 TI - [Call in an anesthesiologist immediately!]. PMID- 7990569 TI - [Tetanus vaccination or not?]. PMID- 7990571 TI - [Selective serotonin uptake inhibitors. A new group of antidepressive agents used more and more]. PMID- 7990570 TI - [Big differences in the resistance against urinary tract infections. Knowledge of steering mechanisms is limited]. PMID- 7990572 TI - [A survey of families with hemophilia B in Sweden. Almost all of the examined have unique mutations]. PMID- 7990573 TI - ["Newly discovered" disorders in myocardial ischemia. Disturbed function in spite of good circulation]. PMID- 7990574 TI - [A summary from a Nordic working meeting. Ribavirin therapy of RSV-infected children]. PMID- 7990575 TI - [Hermann Frenzel and the lighted eyeglasses. He introduced a new way to measure vertigo]. PMID- 7990576 TI - [Life-threatening thrombosis caused by umbilical catheters. A common intervention may cause a rare complication]. PMID- 7990577 TI - [Who is going to take care of the fat children?]. PMID- 7990578 TI - [Primary health care anno 1904--a retrospective study. Vacation after 10 years. No pension!]. PMID- 7990579 TI - [Intra-articular injection of hyaluronan in the knee. An effective therapy or placebo?]. PMID- 7990580 TI - [Starting a new Swedish registry of diabetes is a waste of resources!]. PMID- 7990581 TI - [Do not harm the patient with back pain by rehabilitation! Accurate diagnosis is important for the choice of therapy]. PMID- 7990582 TI - [Serious consequences of unconfirmed diagnosis of condylomata]. PMID- 7990583 TI - [Treatment of knee joint arthrosis--a problem?]. PMID- 7990584 TI - [Amiodarone--a warning! Clarify possible thyroid disease before treatment!]. PMID- 7990586 TI - [Ribozyme-based gene therapy of HIV]. PMID- 7990585 TI - [Why is the number increasing? A new method explains the changes in mortality from Parkinson disease and ALS]. PMID- 7990587 TI - [Cough is predisposing for urinary incontinence. Women with obstructive pulmonary disease are a risk group]. PMID- 7990589 TI - [Karin Johannison: an echo from the "fin-de-siecle". The ideal woman of that era was the breeding ground of morbidity. Interview by Birgit Wilhelmson]. PMID- 7990588 TI - [A complication in Budd-Chiari syndrome. Heparin therapy caused thrombocytopenia]. PMID- 7990590 TI - [Necessity for an alpha 1-antitrypsin registry. The clinical follow-up of patients is easier]. PMID- 7990591 TI - [UV light during surgery is an alternative to the box]. PMID- 7990592 TI - [A study shows athletic injuries caused by blunt violence. Eye injuries are mostly frequent in indoor squash games]. PMID- 7990593 TI - [Dilemmas of preventive medicine. Giving advice during health examination is a delicate matter]. PMID- 7990594 TI - [Emphasise arguments for higher dosage of proguanil!]. PMID- 7990595 TI - [How to treat suspected peptic ulcer hemorrhage?]. PMID- 7990597 TI - [Transluminal insertion of endovascular prosthesis. A development by which major surgery may be avoided]. PMID- 7990596 TI - [Severe injury and tetanus]. PMID- 7990598 TI - [Transfemoral treatment of abdominal aortic aneurysm. A new way to perform vascular surgery]. PMID- 7990599 TI - [From a vision to reality. Endovascular treatment of aortic aneurysm]. PMID- 7990601 TI - [Ethanol is effective against liver tumors. Ultrasonically guided injections are an alternative to resection]. PMID- 7990600 TI - [Physiological processes control parental behavior. Hormonal ties between mother and child]. PMID- 7990602 TI - [Long-term follow-up after removal of the bundle of His. Radiofrequency ablation is effective against fibrillation]. PMID- 7990603 TI - [Pharmaceuticals plus endoscopic therapy for hemostasis. New therapeutic methods in esophageal varices]. PMID- 7990604 TI - [Care of sexual offenders. Only pharmacologic treatment is effective]. PMID- 7990605 TI - [Muscle spindles in focus. Do stress and static work accelerate the muscle to muscle transmission of pain?]. PMID- 7990607 TI - [Five years after the collapse of the DDR. Residents of the East receive psychiatric care for self-esteem which is at zero point]. PMID- 7990606 TI - [Substantial increase of invasive fungal infections. Recommendations from an expert group. Lakemedelsverket (Drug Administration Office)]. PMID- 7990608 TI - [Health care goals and priorities: what is the target of health care?]. PMID- 7990610 TI - [An insurance is a voluntary agreement between 2 parties]. PMID- 7990609 TI - [One more time: ambulance personnel is health personnel!]. PMID- 7990611 TI - [A language of power confronting the right of the breast cancer patient]. PMID- 7990612 TI - [Dengue fever in travellers to Asia. Development of a vaccine is important]. PMID- 7990613 TI - [Dengue fever. Important differential diagnosis from malaria and typhoid fever]. PMID- 7990614 TI - [Skeletal scintigraphy for detection of metastases. A rapid first-choice method with an acceptable radiation dosage]. PMID- 7990615 TI - [Congenital cataract requires early surgery. A critical limit is at the age of 3 months]. PMID- 7990616 TI - [Care of spinal injuries]. PMID- 7990617 TI - [Clinical auditor. A key position in the development of quality of health care]. PMID- 7990618 TI - [Introductory comment on necrotizing enterocolitis in the newborn infant]. PMID- 7990620 TI - [The effect of buffers in liver preservation solutions on hepatocytes in a model of in vitro preservation and reoxygenation]. AB - In order to answer the question of whether there is an optimal buffer system for the preservation and reoxygenation period in liver transplantation, sodium/potassium phosphate, HEPES, TRIS (THAM), MOPS and histidine/His-HCl buffers were investigated. The buffers were added to an "extracellular" electrolyte composition of preservation solution. The solutions were incubated with in vitro cultures of pig hepatocytes in two different models. I: during cold hypoxia (4 degrees C, PO2 < 0.1 mmHg) for 24 h, and II. during the reoxygenation period of 3 h after preservation in UW solution. Cell viability, cell detachment rate, and LDH and GOT liberation were used as parameters of cell alteration. The lowest amount of enzyme release during the preservation period and reoxygenation was obtained using sodium or potassium phosphate buffer. Rising LDH and GOT liberation rates during preservation and reoxygenation were observed with HEPES and TRIS buffer. The enzyme release induced by these three buffer systems correlated with their pKa values. Higher pH of the preservation solution resulted in higher enzyme leakage from the cells. In contrast, the Histidine/HCl buffer system with low pH led to striking cell damage during preservation as well as during reoxygenation. MOPS, a weak acid with the lowest pH in solution, led to the lowest enzyme release during the preservation period, but to high enzyme release after reoxygenation with standard medium. Incubation of the cultures with MOPS after UW preservation resulted in lower enzyme levels in comparison to the controls. In summary, PBS had the best results in our study. PMID- 7990619 TI - [Necrotizing enterocolitis: symptomatology, diagnosis and therapeutic consequences]. AB - Within a 6-year period ten patients with necrotizing enterocolitis (grade II-III; Bell) have been treated at the University Hospital, Gottingen. The following NEC incidences were calculated: birth weight < 1000 g: 2.4% (3/123); 1000-1500 g: 0.6% (2/308); 1501-2000 g: 0.7% (3/436); > 3000 g: approximately 0.006% (2/30,000 live births). In all patients onset of necrotizing enterocolitis (NEC) was associated with typical clinical symptoms such as abdominal distension, feeding problems, bloody stools. Only four out of ten patients had positive blood tests of various inflammatory parameters when diagnosed (C-reactive protein, neutrophil count, I/T-ratio). However, increased CRP levels were observed in all patients during the course of the disease (maximum levels: day 2-4 after diagnosis). During primarily conservative therapeutic management only one out of ten patients developed bowel perforation (day 6 after diagnosis) and immediate surgical treatment was carried out. In addition, in three patients who acquired strictures with obstruction of the colon, elective surgery was performed at a postnatal age of 51-77 days. All patients survived NEC without longterm sequelae. We conclude that a primarily conservative therapeutic regimen-whenever perforation and gangrene are absent-may be an alternative to early surgical intervention in NEC. PMID- 7990622 TI - [PTFE prostheses in infrarenal aneurysms of the abdominal aorta]. AB - Postoperative dilatation of Dacron vascular grafts can lead to aneurysms and rupture of the prosthesis making it necessary to change the graft by operation. Therefore, 15 patients at Lubeck University Hospital underwent replacement of the aorta with PTFE prostheses due to infrarenal aortic aneurysms. Ultrasound measurements 2-12 months postoperatively revealed a dilatation of 11.6% concerning tubular grafts, 11.5% for the shafts and 14.6% for the limbs of bifurcation grafts compared to the higher dilatation rate of Dacron prostheses described in the literature. There was no evidence of anastomotic false aneurysms, thrombosis of the limbs of bifurcation grafts, peripheral embolization or perigraft reaction. In conclusion, PTFE prostheses seem to be a means of preventing patients from having secondary complications as a result of graft dilatation. Based on our early results and the results described in the literature, PTFE prostheses can be regarded as an alternative to dacron prostheses. PMID- 7990621 TI - [The Longmire gastrectomy in the animal model: postoperative changes in fat resorption and the hormones cholecystokinin and secretin]. AB - In this animal study we investigated the absorption of free fatty acids and triglycerides after gastrectomy. The levels of the hormones cholecystokinin and secretin were measured in response to a controlled enteral fat load (Lipofundin 20% MCT emulsion). We studied fat absorption in three groups of animals: the gastrectomy group in which lipid emulsion was administered in the duodenum, and two groups of controls that received the same infusion in the duodenum or stomach, respectively. Infusing the fat load directly into the duodenum, rather than the stomach, resulted in delayed absorption of fatty acids. In the gastrectomized animals there was, in addition, increased absorption of triglycerides. Medium- and long-chain fatty acids were found to be an adequate stimulus for secretion of the gastrointestinal hormones cholecystokinin (CCK) and secretin. In the gastrectomized group, higher baseline levels of both CCK and secretin were observed. CCK showed no response to the lipid stimulus, whereas a secretin response was observed over and above the raised baseline level. The gastrectomized animals showed a markedly restricted growth rate, as measured by body weight; however, they continued to gain weight in a linear fashion up to the end of the study period. No alterations in morphology of CCK-secreting cells were found. PMID- 7990623 TI - [Pressure-volume analysis of wound suction drainage containers and suction capacity of drainage tubes]. AB - Four low-vacuum systems and eight high-vacuum systems were examined with special reference to the pressure-volume relations. The maximum filling volume for adequate transport of wound secretion was determined for each type. The use of a synthetic wound fluid instead of water resulted in a smaller aspiration volume. Enlargement of the tube diameter resulted in a reduced initial vacuum for the low vacuum systems, whereas the high-vacuum systems were not affected. Normal drain tubes were compared with "Ulm drains" and silicon tubes for suction capacity. The suction maximum of normal tubes and silicon tubes was located at the proximal holes of the perforated tubes. The "Ulm drain," with perforation diameter increasing continuously to the distal end of the tube, was found to exert suction even at the more distal part of the tube. It is estimated that this tube allows locally more balanced vacuum in the wound. PMID- 7990624 TI - [Pseudo-aneurysm of the hepatic artery. A rare complication after laparoscopic cholecystectomy]. AB - With the spread of laparoscopic cholecystectomy more and more complications are being reported. For the first time in this paper a pseudoaneurysm of the right hepatic artery as a complication of laparoscopic cholecystectomy in a 55 year old patient is described. During embolization the aneurysm ruptured and an emergency laparotomy was performed. The right hepatic artery was ligated. The postoperative course up to follow-up at 6 months was uncomplicated. PMID- 7990625 TI - [A new suture device for continuous sutures in the intestinal tract]. AB - A new surgical sewing device for continuous sutures of gastrointestinal anastomoses with needle and suture material was used for the first time to construct a latero-lateral enterostomy (functional end-to-end anastomosis) in the small intestine of pigs. In ten animals the course was mainly uneventful during the observation period of 10 days. One animal developed a postoperative anastomotic leakage. In five cases adhesions between the anastomotic region and the small intestine were found on postmortem examination, but there was no evidence of any slight leakage. On the whole, the sewing device operated faultlessly. At present, clinical use seems possible for long sutures, which are time-consuming when sewn manually, but it is still premature. One major disadvantage of the device is its size, which restricts its application to extra abdominal tasks. Nonetheless, the principle of a mechanical device for running sutures should be investigated further. PMID- 7990626 TI - [The effectiveness of standardized follow-up studies after resection of non-small cell bronchial carcinoma]. AB - The outcomes of 190 patients in whom a non-small-cell bronchogenic carcinoma had been resected with curative intent in the Department of Surgery, University of Cologne, between 1. 1. 1977 and 31. 12. 1987 were analysed retrospectively. Sixty seven (35%) of these patients underwent regular, 64 (34%) irregular, and 59 (31%) no standardized follow-up programmes. During follow-up procedures tumour recurrences were detected in 33 patients (25%). Thirteen (39%) of these recurrences were completely asymptomatic at the time of diagnosis. Three recurrences (9%) were resected with curative intent, but the patients died between 14 and 17 months later due to recurrent disease. Seven recurrences (21%) were treated by radiotherapy, three (9%) by chemotherapy, and 20 patients (61%) received no oncologic therapy. The survival rates after diagnosis of recurrence were not affected by the type of treatment or by the presence of clinical symptoms. There is no evidence that long-term results following resection of non small-cell bronchogenic carcinoma can be improved by regular and standardized follow-up programmes. The observed incidence of postoperative pulmonary disorders and the patients' self-assessment underline the necessity for postoperative care after resection of bronchogenic carcinoma. Apart from clinical studies, follow-up should primarily focus on individual symptoms and should no longer include standardized investigations in asymptomatic patients except occasional X-ray checks of the thorax. PMID- 7990627 TI - [Localized benign pleural mesothelioma]. AB - Benign mesothelioma of the pleura is a very rare tumor. The cells responsible originate from either the mesothelium or the submesothelium. This is why such tumors are described in the literature as fibroma of the pleura, mesothelial fibroma, localized fibrous mesothelioma and monophasic spindle cell tumor. Their growth, is very slow taking several years or even decades. In contrast to the more common malignant mesothelioma of the pleura, it is not related to asbestos exposure. This report deals with a 47-year-old woman patient with a giant benign mesothelioma of the pleura in the region of the right thorax, which was completely removed by thoracotomy. PMID- 7990628 TI - [Which laparoscopic interventions are currently reliable for various indications?]. PMID- 7990629 TI - Three-dimensional magnetic resonance imaging evaluation of pediatric tracheobronchial tree. AB - Magnetic resonance imaging (MRI) of the airway has recently emerged as a diagnostic tool for evaluating tracheobronchial obstruction in pediatric patients. Computer-assisted reconstructions of transaxial images have enabled three-dimensional reconstructions of the airway to be manipulated in any plane and visualized in relation to adjacent anatomical structures. Eight patients in whom magnetic resonance imaging was used to diagnose a variety of airway obstructive lesions are presented. A protocol for the evaluation of pediatric tracheobronchial obstruction is presented, with the role of three dimensionally reconstructed MR imaging emphasized. PMID- 7990630 TI - Revision stapes surgery with and without laser: a comparison. AB - In this study, the results of 76 revision stapes surgeries performed from 1974 to 1992 were reviewed. Either the KTP or the argon laser was used in 40 operations. Prosthesis problems were the most common cause for revision (63%) followed by eroded/necrotic incus (29%) and adhesions (29%). Overall "success" in air-bone gap closure (air-bone gap < or = 10 dB) was 46% for first revisions and 33% for second or greater revisions. The "improvement" rate (air-bone gap < or = 20 dB) was 65% for first revisions and 53% for second or greater revisions. There was no statistically significant difference in hearing results between laser surgery and conventional technique. However, an absence of adhesions was noted when the laser had been used in the primary procedure. PMID- 7990631 TI - Nasal cavity area in term infants determined by acoustic rhinometry. AB - The present study was undertaken to determine whether a modification to commercially available acoustic rhinometry (AR) instrumentation might allow equipment designed for use in adults to determine accurately the nasal cavity configuration of infants and children. The standard wave tube was replaced with a version having a narrow (0.312-cm2) internal diameter (ID). Before use with neonates, the accuracy of this instrument was evaluated using the nasal cavity of a full-term infant cadaver. Acoustic nasal area curves were compared to area measurements of polyvinylsiloxane nasal casts and direct volume measurements of the specimen. AR correlated well with nasal cast data (r = .88) for total nasal cavity area. The acoustic method underestimated the total area at the nasal valve by only 1.8 mm2 (22.1 mm2 vs. 23.9 mm2) and overestimated choanal area by 10 mm2 (56.9 mm2 vs. 46.9 mm2). In addition, AR measured total nasal volume to within 5.2% of the value obtained by direct measurement. In a cohort of 10 normal, term infants, the mean acoustic value for total nasal valve area was 19.2 +/- 0.05 mm2 and for total nasal volume was 1.76 +/- 0.53 cm3. This, the first report of nasal area and volume information in live infants, suggests that the modified AR device has utility both in airway research and as a nasal patency screening tool in the pediatric population. PMID- 7990632 TI - Papillary squamous neoplasms of the head and neck. AB - Papillary squamous neoplasms of the upper respiratory tract are rare variants of squamous cell carcinoma and are related temporally to proliferative verrucous leukoplakia. Fifty-two cases of papillary squamous neoplasms were selected from 2366 cases of squamous cell carcinoma. This is the first study to characterize the biological behavior of papillary squamous neoplasms. Papillary squamous neoplasms exhibit two distinct, yet sometimes overlapping, histologic patterns including an exophytic papillary and an inverting verrucous morphologic appearance. A high rate of synchronous or metachronous lesions were found, especially with the inverting-type of papillary squamous neoplasm. Stage T3 and T4 lesions had a high rate of neck metastasis. Early surgical intervention and close long-term follow-up is mandatory. PMID- 7990633 TI - Otitis media (silent): a potential cause of childhood meningitis. AB - Sixteen temporal bones from 8 infants with otitis media, who died of meningitis, and 6 controls from infants with only otitis media, were studied histologically. All bones contained middle ear effusion and residual mesenchyme, but, unlike the controls, the meningitic cases showed considerable histopathological tissue changes of chronic and acute otitis media and chronic inflammatory cells in the round window membrane and within the perilymph, the modiolus, and the cochlear aqueduct, suggesting the latter as likely portals from the inner ear to the meninges. Since all tympanic membranes were intact and 3 were histologically normal, this silent route of infection warrants medical vigilance. PMID- 7990634 TI - Long-term results of treatment for glomus jugulare and glomus vagale tumors with radiotherapy. AB - Since 1954, 39 cases of glomus jugulare or vagale tumor have been treated by the authors with radiotherapy. The initial results with orthovoltage (280 kV) therapy were unpredictable, but 30 patients with 32 tumors treated with megavoltage radiotherapy (Cobalt-60 [60Co] or linear accelerator) have shown either no evidence of recurrence or complications, with one exception, or died of causes unrelated to their glomus tumor. Megavoltage radiotherapy is recommended for primary treatment of all glomus tumors that present with evidence of bone invasion or nerve involvement. PMID- 7990635 TI - External beam irradiation alone or combined with neck dissection for base of tongue carcinoma: an alternative to primary surgery. AB - From 1964 to 1990, 134 patients were treated at the University of Florida with continuous-course external beam irradiation, alone or followed by a planned neck dissection, for T1 (n = 17), T2 (n = 47), T3 (n = 49), or T4 (n = 21) carcinoma of the base of tongue. The 5-year rate of local control was 90% for stage T1, 92% for T2, 73% for T3, and 35% for T4. Probability of control above the clavicles at 5 years according to modified American Joint Committee on Cancer (AJCC) stage was 100% for stages I and II, 75% for stage III, 84% for stage IVa, and 52% for stage IVb. Probability of relapse-free survival at 5 years was 100% for stages I and II, 68% for stage III, 81% for stage IVa, and 37% for stage IVb. Severe complications occurred in 2% of patients. Compared with surgical resection of the primary tumor, external beam radiotherapy results in similar rates of local control and survival with a lower risk of severe complications. PMID- 7990637 TI - Carcinoma of the soft palate and anterior tonsillar pillar. AB - The results after treatment of a total of 52 patients between 1974 and 1990 for squamous cell carcinoma of the soft palate and anterior tonsillar pillar by surgery, radiotherapy, or a combination of the two are reported in the present study. Of the 45 patients who were treated for cure, 38 were treated by surgery, followed by radiotherapy in 19 patients (50%). Five patients received definitive radiotherapy only, and 2 were treated by other modalities such as intra-arterial methotrexate and carbon dioxide (CO2) laser. Absolute and determinant 5-year survival rates were 62% and 77%, respectively. Sixty-four percent of patients survived 5 years recurrence-free, and 27% developed multiple primary tumors in the head and neck. Tumor stages III and IV were shown to decrease survival by half compared to stages I and II. A 42% occult nodal metastases rate was observed, and 3 of 11 patients experienced regional relapse in an untreated neck. From this review it appears that surgery, combined with postoperative radiotherapy when indicated, is an effective form of treatment for carcinoma of the soft palate and anterior tonsillar pillar. PMID- 7990636 TI - Hypericin uptake in rabbits and nude mice transplanted with human squamous cell carcinomas: study of a new sensitizer for laser phototherapy. AB - Tissue uptake and biodistribution of hypericin was measured in rabbits and in nu/nu mice xenografted with P3 human squamous cell carcinoma to assess the value of this dye as an in vivo sensitizer for laser photoinactivation of solid tumors. Hypericin has absorption maxima at 545 and 590 nm with a fluorescence emission peak at 640 nm in ethanol. Dye uptake after intravenous injection was tested at 4 and 24 hours in rabbit tissues by ethanol extraction and quantitative fluorescence spectrophotometry. Maximum dye levels were seen at 4 hours in most vascular organs with lung having fivefold higher uptake than spleen followed by liver, blood, and kidney. Mice were examined after 2, 4, 6, 8, and 24 hours and after 3 and 7 days for dye uptake. The peak concentration of hypericin in murine organs was reached at 4 hours with uptake per gram of tissue as follows: lung > spleen > liver > blood > kidney > heart > gut > tumor > stomach > skin > muscle > brain. Elimination of hypericin was rapid in most murine organs with residual dye under 10% of maximum by 7 days compared to 25% to 30% retention for the squamous cell tumors and several normal tissues. These results suggest that hypericin may be a useful photosensitizer for KTP/532 laser interstitial therapy of human cancer. PMID- 7990638 TI - Mucociliary activity and ultrastructural abnormalities of regenerated sinus mucosa in rabbits. AB - The purpose of this study was to observe histologic findings in the regenerated maxillary sinus mucosa and restoration of ciliary activity by measuring the speed of mucociliary transport after complete surgical removal of the maxillary sinus mucosa. The maxillary sinuses of 32 rabbits were opened anteriorly and one side of the sinus mucosa of each animal was completely removed. In 16 animals, the natural ostia were widened, and, in another 16 animals, the natural ostia were left undisturbed. The contralateral, sham-operated sinus was used as a control for each animal. The animals of each group were reanesthetized and the maxillary sinuses were reopened at planned intervals. The speed of mucociliary transport toward the maxillary ostium, determined by India ink particle movement, was reduced to 6.4 mm/min, whereas it was 10.8 mm/min in the control side. Beating cilia were observed in 16% by dark-field microscopy, in contrast to 66% in the control sinus. Pseudostratified columnar epithelia without cilia were present in 12%, with the remaining consisting of pseudostratified ciliated columnar epithelia (88%). Light microscopic examination showed increase in submucosal fibrotic proliferation, decrease in submucosal glands, and infiltration of inflammatory cells. Under transmission electron microscopy, abnormal cilia such as compound cilia or edematous cilia were frequently found in the regenerated specimens. These observations suggest that mucociliary clearance of the regenerated sinus mucosa may be significantly diminished compared with that of the original mucosa. PMID- 7990639 TI - Total conservative parotidectomy for primary benign pleomorphic adenoma of the parotid gland: a 25-year experience with 229 patients. AB - A 25-year experience with total conservative parotidectomy for primary benign pleomorphic adenoma (PBPA) of the parotid gland in a consecutive series of 229 patients has been reviewed. This study focuses on survival, morbidity, PBPA recurrence, postoperative facial nerve dysfunction, and Frey's syndrome. Surgical death was never encountered in this study. The overall incidence for postoperative hemorrhage, hematoma, seroma, skin necrosis, great auricular nerve schwannoma, and keloid scar was 1.7%, 6.1%, 4.8%, 0.9%, 15.7%, and 8.3%, respectively. Five-, 10-, 15-, and 20-year PBPA control actuarial rate was 99.6%. The overall incidence for temporary facial paresis and paralysis was 64.6% and 5.6%, respectively. Kaplan-Meier actuarial analysis demonstrated that paresis recovery was noted until the eighteenth postoperative month. The overall incidence for permanent facial paresis and paralysis was 3.9% and 0%, respectively. None of the following variables--sex, age, PBPA size, PBPA location, PBPA contact with the facial nerve, inadvertent PBPA spillage, or surgeon's experience--was statistically related to PBPA recurrence and facial nerve dysfunction. The overall incidence for Frey's syndrome was 65.9%. Kaplan Meier actuarial analysis demonstrated the need for a minimal 5-year follow-up to assess Frey's syndrome incidence. The mean age was statistically lower in patients presenting with Frey's syndrome. PMID- 7990640 TI - Relationship between immune complex and total hemolytic complement in endolymphatic hydrops. AB - Recently there has been considerable investigation into the relationship of the immune system and immune disorder to Meniere's disease. Immunoglobulin G (IgG) antibody and complement are both present in endolymphatic fluid and it is possible that endolymphatic hydrops is due to immune complex. The authors' results show that patients with endolymphatic hydrops had elevated levels of circulating immune complex (CIC) of IgG (24.80 micrograms/mL). The levels of functional complement activity (CH50) were significantly lower in patients (249.7 HU) than in controls. Circulating levels of CIC and CH50 were positively correlated. Immunoglobulin G, immunoglobulin M (IgM), and subpopulation of B lymphocytes were elevated, but there was no alteration in subpopulations of T helper, T-suppressor, and natural killer (NK) cells in peripheral blood. PMID- 7990641 TI - Tetracycline sclerosis for treatment of benign lymphoepithelial cysts of the parotid gland in patients infected with human immunodeficiency virus. PMID- 7990642 TI - Changed clinical course and current treatment of acute epiglottitis in adults a 12-year experience. PMID- 7990643 TI - Endoscopic septoplasty. AB - Often there is a need to address the status of the nasal septum during functional endonasal sinus surgery. The outcome of a sinus procedure can be enhanced if the surgeon has better exposure of the operative area or if the patient receives a larger nasal airway, which provides laminar air flow. We present a technique of managing septal deviations and obstructions that adds little additional time to the sinus procedure and allows direct evaluation of the septum with the endoscopes. We describe this relatively simple technique, indications for its use, and results of the first 38 cases. PMID- 7990644 TI - Directory of otolaryngological societies. PMID- 7990645 TI - Central antisecretory and peripheral gastroprotective effects of GBR 12909, a selective dopamine uptake inhibitor. AB - A variety of dopaminergic compounds influence gastric secretion and response to injury. In particular, agonists of the D1 receptor are gastroprotective when given either centrally of peripherally. In the present studies, we show that an indirect dopamine (DA) promoter, GBR 12909, a selective DA uptake inhibitor given ip but not icv, protects against restraint-cold stress-induced gastric mucosal injury. This protection likely occurred through preservation of gastric adherent mucus, since all doses of GBR 12909 resulted in gastric mucus levels at or near control (non-stressed) values. When given, ip, GBR 12909 did not influence basal gastric acid secretion in conscious rats, however, when given icv, GBR 12909 inhibited gastric acid secretion with an ED50 of about 0.5 microgram (1.13 umoles). We conclude that both central and peripheral DA contributes to gastrointestinal integrity through reduction of aggressive elements in the gut as well as by enhancing gastric mucosal defence. PMID- 7990646 TI - Mu, delta, and kappa opiate receptor binding of Tyr-MIF-1 and of Tyr-W-MIF-1, its active fragments, and two potent analogs. AB - The relative binding to mu, delta, and kappa opiate receptors was characterized for the brain peptides Tyr-MIF-1 (Tyr-Pro-Leu-Gly-NH2), Tyr-W-MIF-1 (Tyr-Pro-Trp Gly-NH2), and two fragments of Tyr-W-MIF-1 (Tyr-Pro-Trp and Tyr-Pro-Trp-Gly) previously shown to have antagonist as well as agonist activity in the guinea pig ileum. Tyr-MIF-1 had relatively low affinity (Ki = 1 microM at the mu site) but high selectivity (400- and 700-fold greater affinity for mu over delta and mu over kappa binding). Tyr-W-MIF-1 (Ki = 71 nM at the mu site) showed higher affinity binding to all three sites than Tyr-MIF-1 while retaining 200-fold selectivity for mu over delta and kappa receptors. The affinity of the fragments of Tyr-W-MIF-1 was lower for mu but higher for delta receptors. We also tested two cyclized analogs of Tyr-W-MIF-1 that were about 200-fold more active than the parent compound in producing analgesia. These analogs showed higher affinity binding to all three opiate receptors. One of the analogs showed binding affinity to mu sites (Ki = 1.3 nM) that was within 3-fold of that of the potent analog of enkephalin, DAMGO. Thus, brain peptides with an N-terminal Tyr-Pro, rather than the Tyr-Gly-Gly-Phe sequence typical of other endogenous opiates, can provide high selectivity for mu opiate receptors. Analogs based on one of them, Tyr-Pro Trp-Gly-NH2, show high affinity as well as potent analgesic activity. PMID- 7990647 TI - Immunoregulation of mammalian fertility. AB - Fertility management is a global issue of agricultural, medical, economic, and social consequence. Although many methods have been devised to both inhibit and assist reproduction, more acceptable alternatives are needed. Regulation by immune intervention is a promising technology as applied to livestock, pets, wildlife, and human beings. Outcome is dictated by site within the reproductive axis that is targeted. Fertility is suppressed by immunization against gonadotropin-releasing hormone, gonadotropins, prostaglandin F2 alpha, oxytocin, gonadotropin receptors, and gamete/embryonic antigens. It also is possible to lyse gonadal cells with ligand-antibody hybrid molecules. Ovulation rates are enhanced by vaccination with inhibin. Antibodies to sex steroid hormones have yielded mixed results. Perhaps recombinant viral vectors can be used to deliver reproductive immunogens. A new and simple technique to generate sustained autoimmune reactions to hormones and cellular antigens entails direct gene transfer into somatic cells. Evolving advances in reproductive immunology and biotechnology should furnish us with novel nonsurgical contraceptives and profertility agents that can be efficiently and safely implemented. PMID- 7990648 TI - Induction of adenylate cyclase sensitive dopamine D2-receptors in retinoic acid induced differentiated human neuroblastoma SHSY-5Y cells. AB - Dopamine D2 receptor (D2-receptor) expression and its coupling to Gi sensitive adenylate cyclase was investigated in human neuroblastoma SHSY-5Y cells. Incubation of SHSY-5Y cells in the presence of 100 nM retinoic acid (RA) for 24 hours resulted in phenotypic differentiation accompanied by a 47% increase in D2 receptor mRNA and a significant increase in the specific binding of a D2-receptor antagonist, [3H]YM09151-2. Stimulation of D2-receptors in differentiated cells by LY171-555, a D2-agonist, attenuated cellular cAMP levels by 30%. The effect of LY171-555 on cAMP levels was blocked by the D2-antagonist, (-)sulpride. Application of these drugs to control undifferentiated cells or differentiated cells incubated with vehicle only had no effect on cellular cAMP levels. These studies suggest that differentiated SHSY-5Y cells express functional D2-receptors and will provide a useful model for future studies on the regulation of expression and function of D2-receptors in cellular differentiation of neuronal cells. PMID- 7990650 TI - Endogenous nitric oxide in expired air: effects of acute exercise in humans. AB - Nitric oxide (NO) is present in the exhaled breath of humans and experimental animals, but its physiologic role and cellular source(s) remain to be determined. Possible sites of origin are pulmonary endothelial cells and/or resident macrophages. Here we have tested the hypothesis that changes in cardiovascular status can alter the apparent pulmonary excretion of NO. Exercise on a stationary bicycle produced rapid and reversible increases in pulmonary NO excretion rate, and changes in NO excretion rate during exercise were well correlated with observed changes in heart rate. These results suggest that changes in expired NO during exercise are related to corresponding cardiovascular responses. PMID- 7990649 TI - Changes in nitric oxide precursor, L-arginine, and metabolites, nitrate and nitrite, with aging. AB - The present study was performed to test the hypothesis that excretion of nitric oxide metabolites, nitrate and nitrite, are decreased with progressive aging in rats and that a decrease in nitric oxide precursor, L-arginine, also decreases with aging. Urinary nitrate/nitrite excretory rates and serum L-arginine levels were measured in male Sprague Dawley rats, ranging in ages from 3 to 25 months. Proteinuria increased dramatically with aging. Conversely, urinary nitrate/nitrite excretion decreased by 50% and 80% in rats, aged 12 months and 17 months, respectively. There was no further decrease in urinary nitrate/nitrite excretion in very old rats, aged 23-24 months. Glomerular filtration rate (GFR) was also measured in some of the rats, aged 3-5 mos and 17 mos. GFR was not different between old and young rats, suggesting that a decrease in GFR could not account for the decrease in urinary nitrate/nitrite excretion in the old rats. However, serum L-arginine levels were decreased with aging, by 30% and 50% in rats, aged 13-15 months and 24-25 months, respectively, when compared with young rats. These data confirm our hypothesis and suggest that nitric oxide (NO) production may decrease with aging and that one mechanism by which nitric oxide production could be decreased with age is a lack of the endogenous substrate, L arginine. Because NO has been implicated to be involved in many physiological processes, age-related decreases in NO production could have far-reaching adverse effects in the aging individual. PMID- 7990651 TI - Altered peripheral benzodiazepine receptor binding in cardiac and liver tissues from thyroidectomized rats. AB - We measured the density and affinity of the peripheral benzodiazepine receptor (PBR) ligand, [3H]4'-Cl-diazepam, in cardiac ventricular and liver homogenates from thyroidectomized (TX) Holtzman adult male rats, and compared these data to sham-operated controls. When data from hypothyroid tissues were compared to those of controls, the densities of PBRs were decreased in cardiac ventricles but not in liver tissue. This reduction in cardiac PBR density is opposite to what has been reported for ventricular calcium channel density in hypothyroidism. PBR affinity for the ligand was increased in both the liver and ventricular homogenates from the hypothyroid tissues, but this difference was not seen in membranes prepared from the liver homogenates. Although 4'-Cl-diazepam affinity is reported to vary between tissues from different species, this is the first report of an in vivo hormone treatment induced change in the benzodiazepine type PBR affinity. Liver tissues from both groups failed to show any interaction when radiolabeled [3H]4'-Cl-diazepam was tested against competing concentrations of thyroid hormone analogs. PMID- 7990652 TI - Antigen-induced airway hyperresponsiveness is associated with airway tissue NEP hypoactivity in rats. AB - In the present study, the role of sensory neuropeptides in the airway hyperresponsiveness (AHR) was investigated. First, the effect of the depletion of sensory neuropeptides by systemic capsaicin treatment on the AHR to acetylcholine (ACh) induced by repeated antigenic challenge to sensitized rats was studied. We secondly investigated whether the neutral endopeptidase (NEP) activity was altered at the antigen-induced AHR. Male Wistar rats were sensitized and repeatedly challenged with DNP-Ascaris antigen. Twenty-four hours after the last antigenic challenge, a marked AHR to inhaled ACh (0.001-0.03%) was observed. This AHR was significantly attenuated by systemic capsaicin pretreatment prior to sensitization. On the other hand, in normal rats, the airway responsiveness to inhaled ACh was significantly increased by pretreatment with NEP inhibitor, phosphoramidon (3 mg/kg, i.v.), but the NEP inhibitor-induced effect was no more observed in the antigen-induced AHR rats. Furthermore, it was found that the airway NEP activity was significantly decreased at the antigen-induced AHR. These findings suggest that NEP hypoactivity and resultant increased sensory neuropeptides have an important role in the pathogenesis of antigen-induced AHR in rats. PMID- 7990653 TI - Temperature effect on the action of corticotropin-releasing hormone (CRH) on secretion of immunoreactive beta-endorphin (IR beta EP) in TM3 and AtT-20 cell lines. AB - Testicular function is sensitive to chemical and thermal stresses. To investigate the effects of small temperature changes on CRH-stimulated beta EP release, we employed TM3 cells, a mouse prepubertal Leydig cell line that secretes ir beta EP. To monitor beta EP secretion from these cells we used the reverse hemolytic plaque assay. After 3.5 hr incubation of cells with hormone, the EC50 of the CRH dose-response curve at 34 degrees C and 37 degrees C were 0.1 nM and 1 nM, respectively. For comparison, we also investigated the effect of temperature on CRH-stimulated beta EP release from a non-testicular cell line, AtT-20, a mouse anterior pituitary cell line. Using radioimmunoassay to measure ir beta EP levels in the media of AtT-20 cells, the EC50s for the CRH dose-response curve at 34 degrees C and 37 degrees C were 0.2 nM and 2 nM, respectively, at 1 h. After 3.5 h this temperature dependent difference in EC50 was still observed. These results suggest that CRH receptors or post-receptor actions in Leydig cells and anterior pituitary corticotropes are sensitive to small temperature changes. PMID- 7990654 TI - Mass spectrometric detection of preproenkephalin A-derived peptides in bovine pituitary. AB - A new analytical system, including chromatography separation, enzyme digestion, radioimmunoassay detection, and mass spectrometry characterization, has been designed to detect native preproenkephalin A-derived peptides in the bovine pituitary. The direct evidence of these intact peptides was provided by the mass spectrometric detection of the (M+H)+ ions of ME-Lys at m/z 702 and of ME-Arg at m/z 730, following trypsin digestion and the detection of ME-like immunoreactivity in HPLC fractions. PMID- 7990655 TI - Hepa-1 enzyme induction assay as an in vitro indicator of the CYP1A1-inducing potencies of laboratory rodent diets in vivo. AB - The Hepa-1 enzyme induction assay (assay of the induction of CYP1A1 catalytic activities in the Hepa-1 mouse hepatoma cell line by various compounds or mixtures) was evaluated as an in vitro indicator of the CYP1A1-inducing potencies of laboratory rodent diets in vivo. C57BL/6J mice were fed for three weeks four selected commercially available diets (one semisynthetic and three standard natural ingredient diets) exhibiting different enzyme-inducing effects in the Hepa-1 assay. beta-Naphthoflavone mixed in a semisynthetic diet (33 and 330 mg/kg of diet) was used as a model inducer. CYP1A1-dependent enzyme activities (aryl hydrocarbon hydroxylase and 7-ethoxyresorufin O-deethylase) were measured in the small intestinal mucosa and liver. There was good agreement between the induction of CYP1A1 in vitro and in vivo: the rank order of the enzyme activities elicited by the diets was the same in the mice as in the Hepa-1 cells. The standard diets were less effective inducers than beta-naphthoflavone in the Hepa-1 cells and in the mice, especially in the small intestinal mucosa. The Hepa-1 enzyme induction assay thus seems to be a mechanistically sound, reliable and sensitive in vitro indicator of the CYP1A1-inducing potencies of laboratory rodent diets in vivo. PMID- 7990656 TI - In vitro inhibition of mammary cell growth by lactoferrin: a comparative study. AB - The effect of lactoferrin (Lf) on mammary epithelial cell growth in culture was tested in a comparative study of bovine and human Lf. Bovine Lf was inhibitory to growth of a bovine mammary epithelial cell line, both in the presence and absence of fetal bovine serum in the medium. The growth inhibition activity of bovine Lf was not affected by iron-saturation status of the protein. In contrast with bovine Lf, human Lf had minimal inhibitory activity on bovine cell growth in the presence of serum, and cell growth was stimulated by human Lf in the absence of serum. In the latter case, human Lf may have acted as an iron-transport protein for the cells. Bovine Lf and human Lf had no effect on growth of MCF-7 human breast tumor cells and only minimal inhibitory activity toward the MDA-MB 231 human breast tumor cell line. The effect of bovine Lf on bovine mammary epithelial cells could be prevented by immunoneutralization of the Lf. These results indicate that Lf can be inhibitory to growth of mammary epithelial cells in culture, but this response to specific for the species origin of the Lf and of the mammary cell. PMID- 7990657 TI - Oleuropein protects low density lipoprotein from oxidation. AB - The Mediterranean diet, rich in fruit, vegetables, grain, and vegetable oil (mainly olive oil) is correlated with a lower incidence of coronary heart disease (CHD). Natural antioxidants contained in the Mediterranean diet might also play a role in the prevention of cardiovascular diseases, through inhibition of LDL oxidation. We tested this hypothesis "in vitro" by inducing LDL oxidation with copper sulphate and preincubating the samples with oleuropein, the bitter principle of olives, that is one of the major components of the polyphenolic fraction of olive oil. Oleuropein 10(-5) M effectively inhibited CuSO4-induced LDL oxidation, as assessed by various parameters. We demonstrate in this investigation that polyphenolic components of the Mediterranean diet interfere with biochemical events that are implicated in atherogenetic disease, thus proposing a new link between the Mediterranean diet and prevention of CHD. PMID- 7990658 TI - Distribution of cholesterol among its carriers in the bile of male and female hamsters. AB - The distribution of cholesterol among its carriers was studied in the bile of male and female hamsters. Sasco hamsters (Sasco Inc., Omaha, NE) were fed a semipurified diet with 0.0% cholesterol and 4% butterfat (group 1, males; group 4, females); a semipurified diet with 0.3% cholesterol and 1.2% palmitic acid (group 2, males; group 5, females); and a semipurified diet with 0.3% cholesterol and 4% safflower oil (group 3, males; group 6, females). At the end of six weeks, gallstones were found only in male hamsters receiving both cholesterol and dietary fat (fatty acid) (incidence of cholesterol stones: 90% in group 2; 22% in group 3). The biliary cholesterol carriers were separated and isolated from the bile of the hamsters by gel filtration chromatography, using the method of Pattinson [Pattinson, N.R., Willis, K.E., and Frampton, C.M. (1991) J. Lipid Res. 32, 205-214]. In those male hamsters that formed cholesterol gallstones, significant amounts of cholesterol were present in the void volume which contained large cholesterol phospholipid vesicles (void volume vesicles) (23% in group 2 and 15% in group 3). Smaller cholesterol/phospholipid vesicles were eluted next (fractions 30-45) and contained 15% of biliary cholesterol in group 2 and 21% in group 3. The remainder of the cholesterol was associated with mixed cholesterol/phospholipid/bile salt micelles. The cholesterol/phospholipid ratio was larger in both the void volume vesicles and small vesicles (2.40 and 1.48 in group 2; 2.56 and 1.33 in group 3, respectively) compared to the micelles (about 0.3 in groups 2 and 3).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7990659 TI - Arachidonic acid and eicosapentaenoic acid stimulate type II pneumocyte surfactant secretion. AB - Arachidonic acid and its leukotriene metabolites have been shown to stimulate surfactant secretion by alveolar type II cells. The present study was undertaken to determine the effects of various unsaturated fatty acids, including eicosapentaenoic acid, on surfactant secretion. Surfactant secretion was expressed as the percent of [3H]choline-derived phospholipids released into culture medium by type II pneumocytes of adult rats. Consistent with the earlier findings, arachidonic acid stimulated secretion in a concentration-dependent fashion (3.5-21 microM), doubling baseline secretion at 21 microM. Eicosapentaenoic acid was found to be equally effective as arachidonic acid in stimulating secretion. A comparison with palmitic, oleic and linoleic acids revealed that highly unsaturated fatty acids stimulated secretion to the greatest extent. This was supported by a positive correlation between degree of unsaturation (i.e., 0, 1, 2, 4 and 5 double bonds) and stimulation of surfactant secretion. In the present study, exogenous leukotriene E4 (10(-13)-10(-6) did not stimulate surfactant secretion. Neither nordihydroguairetic acid (0.1 microM) nor indomethacin (0.1 microM) affected arachidonic acid-stimulated secretion. The stimulatory effects of arachidonic acid and eicosapentaenoic acid on surfactant secretion were related to the highly unsaturated nature of the fatty acids and were not mediated by increased levels of cyclic adenosine monophosphate or calcium. PMID- 7990660 TI - Evidence that palmitic acid is absorbed as sn-2 monoacylglycerol from human milk by breast-fed infants. AB - Milk fatty acids consist of about 20-25% palmitic acid (16:0), with about 70% of 16:0 esterified to the sn-2 position of the milk triacylglycerols. Hydrolysis of dietary triacylglycerols by endogeneous lipases produces sn-2 monoacylglycerols and free fatty acids, which are absorbed, reesterified, and then secreted into plasma. Unesterified 16:0 is not well absorbed and readily forms soaps with calcium in the intestine. The positioning of 16:0 at the sn-2 position of milk triacylglycerols could explain the high coefficient of absorption of milk fat. However, the milk lipase, bile salt-stimulated lipase, has been suggested to complete the hydrolysis of milk fat to free fatty acids and glycerol. These studies determined whether 16:0 is absorbed from human milk as sn-2 monopalmitin by comparison of the plasma triacylglycerol total and sn-2 position fatty acid composition between breast-fed and formula-fed term gestation infants. The human milk and formula had 21.0 and 22.3% of 16:0, respectively, with 54.2 and 4.8% 16:0 in the fatty acids esterified to the 2 position. The plasma triacylglycerol total fatty acids had 26.0 +/- 0.6 and 26.2 +/- 0.6% of 16:0, and the sn-2 position fatty acids had 23.3 +/- 3.3 and 7.4 +/- 0.7% of 16:0 in the three-month old exclusively breast-fed (n = 17) and formula-fed (n = 18) infants, respectively.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7990661 TI - In vitro activation of mouse skin protein kinase C by fatty acids and their hydroxylated metabolites. AB - To understand how dietary fatty acids differentially modulate mouse skin tumorigenesis, the ability of specific fatty acids and their derivatives to activate murine epidermal protein kinase C (PKC) in vitro was investigated. Total PKC from untreated female SSIN mouse skin was partially purified and incubated with specific fatty acids at concentrations up to 300 microM in the presence of Ca2+ and phosphatidylserine. The cis-unsaturated fatty acids tested, ranging from 16:1 to 22:6, stimulated PKC activity in a similar dose-dependent manner with an approximate threefold maximum increase over control. Neither the number of cis double bonds nor the chainlength of these fatty acids affected their relative ability to activate PKC. trans-Fatty acids, with the exception of linoelaidic acid (t,t-18:2n-6), exhibited about half of the potency of their corresponding cis-isomers in stimulating PKC at the plateau concentration (200 microM) or lower. Substitutions close to the double bond on cis-fatty acids abolished their ability to activate PKC. The hydroxylated metabolites of arachidonic acid (20:4n 6) and linoleic acid (c,c-18:2n-6), i.e., the hydroxyeicosatetraenoic acids (HETE) and hydroxyoctadecadienoic acids (HODE), also activated mouse skin PKC in vitro, but only about half as effectively as did the respective parent fatty acids. The results suggest that both hydroxyl substitution and trans configuration of HETE and HODE are responsible for their reduced ability to activate PKC. Overall the data suggests that the reduced skin tumor yield observed in mice fed diets high in c,c-18:2n-6 is not likely to be due to differences in the ability of c,c-18:2n-6 or 20:4n-6, or their metabolites, to activate PKC. PMID- 7990662 TI - Lymphatic absorption of oxidized cholesterol in rats. AB - The absorption of cholesterol and of cholesterol oxidation products (oxidized cholesterols) was compared in lymph-cannulated rats. We found that the lymphatic absorption of an intragastrically administered, emulsified lipid meal containing 25 mg of cholesterol or 25 mg of oxidized cholesterols, within 24 h, was approximately 67 and 30%, respectively. The absorption rate of individual oxidized cholesterols differed considerably and was approximately 30% for 7 alpha hydroxycholesterol, 42% for 7 beta-hydroxycholesterol, 32% for 5 beta epoxycholesterol, 28% for 5 alpha-epoxycholesterol, 15% for cholestanetriol and 12% for 7-ketocholesterol. Moreover, cholesterol oxidation products delayed the absorption of oleic acid as triolein. Approximately 35 and 48% of cholesterol was recovered in chylomicrons (CM) and very low density lipoprotein (VLDL), respectively. In contrast, 54 and 40% of the oxidized cholesterols was recovered in CM and VLDL, respectively, although there was a significant difference in the distribution of individual oxidized cholesterols. The results of the present study indicate that oxidized cholesterols are absorbed to a lesser extent than is cholesterol, that they disturb fat absorption and that they distribute differently between lymphatic lipoproteins. PMID- 7990663 TI - Effects of n-3 and n-6 fatty acids on the activities and expression of hepatic antioxidant enzymes in autoimmune-prone NZBxNZW F1 mice. AB - Menhaden fish oil (FO) containing n-3 fatty acids dramatically extends the life span and delays the onset and progression of autoimmune disease in (NZBxNZW)F1 (B/W) female mice as compared to those fed corn oil (CO) rich in n-6 lipids. As an inefficient antioxidant defense system has been linked to autoimmune diseases, the present study was undertaken to determine whether the protective action of n 3 lipids is mediated through their antioxidant defense system. Weanling B/W mice were fed a nutritionally adequate, semipurified diet containing CO or krill oil (KO) or FO at 10% level (w/w) ad libitum until the mice were 6.5 months old. All diets contained the same level of vitamin E (21.5 mg/100 g diet). We compared the effects of feeding n-6 and n-3 lipids on survival, kidney disease, hepatic microsomal lipid composition, peroxidation, and on the activity and mRNA expression of the antioxidant enzymes catalase, glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD) in 6.5-month-old B/W mice. The results showed that when compared to livers from CO-fed mice, livers from KO- and FO-fed mice showed: (i) significantly higher (P < 0.001) activities and expression of CAT, GSH-Px and SOD; (ii) significantly lower (P < 0.001) arachidonic acid (20:4n-6) and linoleic acid (18:2n-6) and higher (P < 0.001) eicosapentaenoic acid (20:5n-3) and docosahexaenoic acid (22:6n-3) levels in hepatic microsomes; and (iii) significantly lower (P < 0.001) estimated peroxidation indices and thiobarbituric acid reactive substances generation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7990664 TI - Serum fatty acid profiles in cystic fibrosis patients and their parents. AB - Fatty acid compositions of the major serum lipid classes from 43 cystic fibrosis (CF) homozygotes (CF patients), 36 obligate heterozygotes (parents of CF patients) and 34 controls were determined by capillary gas chromatography. Fatty acid compositions of the homozygote CF patients were skewed in the direction of relative essential fatty acid deficiency in comparison with the controls. Less pronounced, but similar deviations from normal, were observed in the heterozygotes. Homozygotes with normal fatty acid compositions and heterozygotes with considerably disturbed fatty acid profiles were found. PMID- 7990665 TI - The lipid composition of selected tissues from a Mediterranean monk seal, Monachus monachus. AB - The lipid composition of blubber, brain, muscle and heart from a Mediterranean monk seal Monachus monachus (an endangered species) were examined to allow comparisons with more common species of seals. Only neutral lipids (mainly triacylglycerols) were detectable in the blubber lipids, whereas polar lipids predominated in the heart and in the brain. Neutral and polar lipids comprised almost equal proportions in both liver and muscle. Choline glycerophospholipids (CGP) were the major polar lipids, followed by ethanolamine glycerophospholipids (EGP) in the liver, heart and muscle. Cerebrosides accounted for 28.8% of the brain lipids. All lipid classes of the liver contained high levels (31-47%) of polyunsaturated fatty acids (PUFA), with the exception of phosphatidylserine. The total proportion of n-6 PUFA exceeded that of n-3 PUFA in all lipid classes of the liver, due mainly to the high levels of 20:4n-6. The highest level of 20:4n-6 occurred in phosphatidylinositol, where it comprised 32.4% of the total fatty acids. The CGP and EGP of the brain contained lower levels of PUFA than those of the liver, muscle and heart. Alkenyl ethers accounted for 35.8% of the total long chain moieties in brain EGP. The fatty acid composition of blubber triacylglycerols differed from those of the lipid classes from other tissues in that it had a very low ratio of n-6 to n-3 PUFA (0.3) as a result of a lower content of 20:4n-6. PMID- 7990666 TI - Metabolism of long-chain fatty acids, alcohols and alkylglycerols in the fish parasite Paratenuisentis ambiguus (Acanthocephala). AB - Specific differences between the acyl composition of lipids of the helminth Paratenuisentis ambiguus and its host eel, as shown previously, prompted us to study the lipid metabolism in this intestinal fish parasite. Adults and larvae of P. ambiguus were fed various lipid precursors, e.g., fatty acids, long-chain alcohols and 1-O-alkylglycerols, which may occur as common nutrients of intestinal parasites. Incorporation of [1-14C]palmitic acid into neutral and polar lipids was found to be similar under aerobic and near-anaerobic conditions. In adult parasites maintained in culture medium supplemented with glucose, [1 14C]palmitic acid was incorporated mainly into triacylglycerols and phosphatidylcholines, whereas [1-14C]oleic acid was incorporated preferentially into triacylglycerols. In fasted adults, as well as in larvae, [1-14C]oleic acid was mainly transferred to phosphatidylcholines. Lipolytic activity was detected in adult parasites that had been incubated with radioactive trioleoylglycerol. [1 14C]Hexadecan-1-ol was oxidized in P. ambiguus at a high rate to labeled palmitic acid, which was incorporated into various lipid classes of P. ambiguus. Small but significant proportions of radioactivity from hexadecan-1-ol were incorporated into ether glycerolipids of the parasite. A more direct precursor in ether glycerolipid metabolism, i.e., rac-1-O-[1'-14C]hexadecylglycerol, was incorporated into alkyl and 1'-alkenyl moieties of choline and etha-nolamine ether-glycerophospholipids of P. ambiguus in high yield. High proportions of labeled diacylglycerols, triacylglycerols and steryl esters were detected in surface lipids as well as lipid extracts of the culture media after incubation of P. ambiguus with [1-14C]palmitic or [1-14C]oleic acids.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7990667 TI - An improved spectrophotometric triiodide assay for lipid hydroperoxides. AB - A spectrophotometric method is described for the measurement of lipid hydroperoxides, to a lower limit of 0.5 nmoles, based on the formation of triiodide ions measured at the absorbance maximum of 365 nm. The assay mixture, which was modified from an earlier published procedure [El-Saadani, M., Esterbauer, H., El-Sayed, M., Goher, M., Nassar, A.Y., and Jurgens, G. (1989) J. Lipid Res. 30, 627-630], contains 18% methanol together with nonionic and cationic detergents, and is designed so that the hydroperoxides to be measured can be added in either water or methanol. By incubating the reaction mixture at 50 degrees C for 30 min, less-reactive hydroperoxides can be measured with the same fidelity as more-reactive ones. Under these conditions, the assay can be carried out under ordinary room lighting and without special protection from ambient oxygen with absorbance values being stable up to 15 h. Enzymatic standardizations showed that the triiodide method gave comparable results for H2O2, cumene hydroperoxide, linoleic acid hydroperoxide, phosphatidylcholine hydroperoxide, and a photooxidized tissue extract containing a mixture of hydroperoxides. The triiodide assay is recommended primarily for measuring purified hydroperoxides. PMID- 7990668 TI - A microprecipitation technique suitable for measuring alpha-lipoprotein cholesterol. AB - A semi-automated method has been developed for determining alpha-lipoprotein cholesterol values. Precipitation of apolipoprotein B containing lipoproteins takes place in wells of microtiter plates after 100 microL of serum are mixed with 20 microL of a heparin/MnCl2 solution. A Beckman (Fullerton, CA) Biomek 1000 work station is used to transfer sera, supernatants and reagents between tubes and microtiter plates. Supernatant cholesterol is determined enzymatically, and absorbances are read at 490 nm using a Molecular Devices Corporation (Palo Alto, CA) plate reader. Values obtained on both fresh and frozen serum samples agreed with corresponding data obtained at the Centers for Disease Control (CDC; Atlanta, GA). For the fresh samples, the average bias was 2.87%. The within-run coefficients of variations were between 2.2 and 0.6% for the data obtained on CDC frozen control pools. The results indicate that the semi-automated method is suitable for obtaining accurate and precise data for alpha-lipoprotein cholesterol. The method lends itself to the analysis of large numbers of samples and is particularly suited for the study of lipoproteins of small mammals. PMID- 7990669 TI - Short, shorter, shortest. PMID- 7990670 TI - Can aspirin prevent and treat pre-eclampsia? PMID- 7990671 TI - Keeping up with neonatal infection: designer bugs, Part II. PMID- 7990672 TI - Congenital syphilis: are we missing infected newborns? PMID- 7990674 TI - Support groups: working side by side with parents. PMID- 7990673 TI - Infant botulism. PMID- 7990675 TI - Useful tools in patient teaching--interviewing skills. PMID- 7990676 TI - FOCA: a step backward for women's health care. PMID- 7990677 TI - Instrument construction: Part II. PMID- 7990678 TI - Update on metoclopramide (Reglan). PMID- 7990679 TI - [Pathologic findings in diethylene glycol poisoning]. AB - We are reporting the necropsy findings of 7 patients poisoned with diethylene glycol-contaminated propolis (a rubbery substance produced by bees from vegetal resins). Besides the well-known features of hydropic necrosis of centrolobular areas in the liver and renal tubules we found acute pancreatitis with diffuse enzymatic fat necrosis which in two of the cases was considered the secondary cause of death, and acute demyelinating lesions in the central and peripheral nervous system. Six out of the 7 cases showed glomerular PAS-positive arteriolar hyalinosis at the vascular pole, in two of them widely disseminated. Differing from the findings reported in ethylene glycol poisoning we could not find calcium oxalate crystals in any of the cases. The pancreatic, central and peripheral nervous system lesions as well as the glomerular arteriolar hyalinosis have not been previously described in the literature in relation with diethylene glycol poisoning. PMID- 7990680 TI - [Incidence and probable etiology of toxic agranulocytosis in a definite population in the province of Buenos Aires (1963-1976)]. AB - The medical records of 55 patients with toxic agranulocytosis (unrelated to radiation, anticancer drugs or known industrial toxics) were reviewed in a well defined population of the Province of Buenos Aires during 1963-1976. There were 65 episodes in 30 women and 25 men, age average 49 years. Nine patients repeated the episode by reexposure to the same drug. The annual incidence rate was 8.4 cases per million/year. Nineteen (35.5%) of the patients died. Forty-three episodes (64.3%) were associated with analgesic-antipyretics, mainly dipyrone (34 cases). In most situations, drugs were prescribed for mild complaints such as pharyngitis, arthralgias or abdominal pain. Although toxic agranulocytosis is an infrequent disease, its relationship with drugs is well known and its mortality remains high. PMID- 7990681 TI - [Role of nitric oxide in alterations of the systemic and splanchnic hemodynamics in a experimental model of portal hypertension]. AB - Recent experimental studies have suggested that an increase in the synthesis of nitric oxide, a powerful vasodilator secreted by endothelial cells, plays a role in the hemodynamic disturbances associated to portal hypertension. The present study was addressed to investigate the effects of L-NNA (a specific inhibitor of nitric oxide) on systemic and splanchnic hemodynamics in portal hypertensive rats, induced by partial portal vein ligation. Intravenous infusion of L-NNA (50 ug/kg/min) significantly increased systemic blood pressure and decreased cardiac output as measured by radiolabeled microspheres. A significant increase in systemic and splanchnic vascular resistance was also observed in L-NNA-treated rats; whereas portal blood flow decreased significantly, L-NNA did not modify portal pressure. Pretreatment with L-arginine (300 mg/Kg, i.v.) prevented the hemodynamic changes induced by L-NNA. Similar values of endotoxin levels were detected in both groups of animals. In the control group, L-NNA caused a mild but significant increase of mean arterial pressure; no significant changes on the other hemodynamic parameters were observed. These results suggest that an increase in endogenous synthesis of nitric oxide may play an important role in hemodynamic disturbances associated with chronic portal hypertension. PMID- 7990683 TI - Papillary hyperplasia and cholesterolosis of the gallbladder. AB - Papillary hyperplasia of the gallbladder was found in 376 patients (28.4%) and cholesterolosis in 206 (15.6%) of 1323 cholecystectomies. An association between these pathological alterations was found (p < 0.001). Papillary hyperplasia was interpreted as a morphological adaptation of the mucosa to permit a greater absorption of cholesterol from the gallbladder lumen to the blood capillaries. By means of this peculiar hyperplasia the surface of interchange increases and, therefore, absorption would be facilitated. It is suggested that papillary hyperplasia could be induced by the increase of bile pressure in the extrahepatic bile ducts and/or by the concentration of bile cholesterol. PMID- 7990682 TI - Biochemical markers of acromegalic activity. AB - Against a clinical score we compared the effectiveness of three biochemical markers of acromegalic activity: a) growth hormone response to i.v. thyrotropin releasing hormone, b) growth hormone suppression one hour after an oral glucose load, c) basal plasma IGF-I levels. In 21 patients we obtained 39 observations comprising the four parameters. According to the clinical score, patients were divided into three groups: group I = patients before surgery; group II = improved but still clinically active; group III = clinically inactive. After i.v. thyrotropin-releasing hormone, abnormal observations increased although the patients improved clinically, so that this test was excluded from statistical analysis. Abnormalities in plasma IGF-I levels and in GH suppression after oral glucose were similarly frequent in the groups studied: both 100% in group I, both 71.4% in group II, 27.3% vs. 18.2% in group III (p > 0.05). Both tests made exactly the same contribution to the other's capacity to detect acromegalic activity: 3 out of 39 observations (5.1%). We conclude that basal plasma IGF-I is the single best biochemical marker to detect acromegalic activity, since it is statistically at least as useful as growth hormone suppression, and is far more simple for the patient and the laboratory. PMID- 7990684 TI - [Neurologic complications by cocaine abuse]. AB - Argentina is facing an increase in cocaine use by adolescents and young adults from every socioeconomic background. It is calculated that up to 10% of all cocaine passing through this country is locally sold and consumed. Nevertheless, local information describing common cocaine-related neurological events is scarce. From August 1988 to March 1993, 13 patients were evaluated with neurological disease associated with cocaine abuse. Among these 13 patients (Table 1), the mean age was 29; 70% were men. Patients most commonly used the nasal route (snorting). Concomitant abuse of other intoxicants, especially alcohol, was frequent (85%). The major neurological complications included one or more seizures (n = 7), ischemic stroke (n = 2) (Fig. 1-2), hemorrhagic stroke (n = 2) associated with arteriovenous malformation (Fig. 3a-b), memory disturbances (n = 1) and paroxysmal dystonia (n = 1). Psychiatric complaints were present in all patients. Mortality was not observed. There was no correlation between the appearance of complications and the amount of cocaine used, or prior experience with this drug. Only one of the 7 patients with seizures had a previous history of seizures. All had generalized tonic-clonic seizures, and one had concomitant absence episodes. Cocaine modulates central neurotransmitters and has direct cerebrovascular effects. The neurological complications appear to be related to cocaine hyperadrenergic effects, striatal dopaminergic receptor hypersensitivity and perhaps vasculitis. Structural changes in the brain of long-term cocaine abusers could explain the persistence of neurologic symptoms after drug withdrawl. PMID- 7990685 TI - [Concomitant immunity against Sarcoma E 100 comparing 2 strains of rats]. AB - Concomitant immunity (IC) is usually defined as the capacity of any animal bearing a progressor tumor to inhibit a second challenge with the same tumor. In order to establish the contribution of the host to the origin of this phenomenon, IC was induced in two lines of rats with a different behavior when challenged with Sarcoma E 100 (SE 100), i.e., line IIMc: 90% take and 100% regression; line "m": 100% take and death. The rats received a second challenge on day 3 (Group II), 7 (III), and 14 (IV), as well as the control groups: II', III' and IV', respectively. The animals reinoculated on day 7 showed a decrease, both in percentage of takes (Fig. 1, III vs III') and tumor surface (Table 1, 2). Likewise, in rats IIMc, a lesser development of the first inoculum (Table 1, Ia vs I') was observed. The Winn assay (Table 3) confirmed the presence of immunocompetent spleen cells (CE) against SE 100 in IIMc rat spleens: namely, 1) immune rats (II), 2) unique tumor bearing rats (IV), 3) first progressor and second negative inoculum (V). In line "m" the percentage of takes was only smaller in the group inoculated conjointly with CE from immune rats (Table 3, VI vs VII). A mere 10% (3/30) of "m" rats were immunized against SE 100. Consequently, these results could attribute the IC, in IIMc rats, to immunological mechanisms, while in "m" it could be due to factor(s) released and/or induced by the first tumor, as proposed by Gorelik. PMID- 7990687 TI - [Renal grafting in a patient with mitral stenosis and undiagnosed pancreatic neoplasm]. PMID- 7990686 TI - [Malignant mesothelioma of the pericardium]. AB - Malignant mesothelioma is a tumor which occurs in one out of every 4,000 patients autopsied for malignant neoplasia. Pericardial location is the least frequently encountered, accounting for less than 2% of the total cardiac tumors. We are presenting here a patient in whom the tumor resulted in a syndrome of cardiac tamponade. It could not be diagnosed in the living patient in spite of having performed a subxiphoideal pericardic biopsy. The patient died suddenly, and the tumor was found during autopsy, infiltrating the right atrium and protruding into the cavity, involving the right coronary artery. This latter situation could have been responsible for the patient's death. Clinical and pathological findings are compared with those of 30 cases found in recent literature. PMID- 7990688 TI - [Chlamydia trachomatis and tubal obstruction sterility]. AB - In order to determine the importance of Chlamydia trachomatis in infertility due to tubal occlusion, the prevalence of C. trachomatis antibody was studied in two populations of Argentine women, pregnant and infertile with tubal occlusion. IgG and IgM against C. trachomatis were determined by indirect immunofluorescence in McCoy cells infected with strain L2Bu434 of C. trachomatis. In infertile women, specific anti-C. trachomatis IgM was detected in 5 out of 32 (15.6%) and IgG in 20 out of 32 (75%). In pregnant women, specific IgM was detected in 4.8% (4/83) and IgG in 20.5% (17/83). The frequency of IgG detection was significantly higher in infertile than in pregnant women (p < 0.000). Thirteen out of 20 (65%) women who underwent laparoscopic examination had evidence of chronic inflammatory disease described as yellowish viscous cysts resembling "frog eggs" in Douglas, utero and/or perihepatitis. Twelve out of fourteen (86%) infertile women with positive serology for C. trachomatis presented one or more of these laparoscopic findings. C. trachomatis antigen was detected in 2 out of 10 tubal biopsies by direct immunofluorescence with monoclonal antibodies although isolation in McCoy cells was negative. Our results show the importance of C. trachomatis in infertility due to tubal occlusion and the need of C. trachomatis diagnosis in routine gynecologic analysis to prevent infertility and neonatal infection. PMID- 7990690 TI - [Error factors in spirometry]. AB - Spirometry is the more frequently used method to estimate pulmonary function in the clinical laboratory. It is important to comply with technical requisites to approximate the real values sought as well as adequate interpretation of results. Recommendations are made to establish: 1--quality control 2--define abnormality 3 -classify the change from normal and its degree 4--define reversibility. In relation to quality control several criteria are pointed out such as end of the test, back-extrapolation and extrapolated volume in order to delineate most common errors. Daily calibration is advised. Inspection of graphical records of the test is mandatory. The limitations to the common use of 80% of predicted values to establish abnormality is stressed. The reasons for employing 95% confidence limits are detailed. It is important to select the reference values equation (in view of the differences in predicted values). It is advisable to validate the selection with local population normal values. In relation to the definition of the defect as restrictive or obstructive, the limitations of vital capacity (VC) to establish restriction, when obstruction is also present, are defined. Also the limitations of maximal mid-expiratory flow 25-75 (FMF 25-75) as an isolated marker of obstruction. Finally the qualities of forced expiratory volume in 1 sec (VEF1) and the difficulties with other indicators (CVF, FMF 25 75, VEF1/CVF) to estimate reversibility after bronchodilators are evaluated. The value of different methods used to define reversibility (% of change in initial value, absolute change or % of predicted), is commented. Clinical spirometric studies in order to be valuable should be performed with the same technical rigour as any other more complex studies. PMID- 7990691 TI - [beta2 adrenergic bronchodilators in chronic asthma. Fixed use or according to necessity?]. PMID- 7990689 TI - [Free radicals of oxygen and superoxide dismutase. Biological and medical aspects]. AB - Oxygen free radicals (OFR) are very reactive and unstable metabolites capable of altering important biomolecules including proteins, lipids and nucleic acids. OFR are regulated by enzymes such as superoxide dismutases (SOD), catalase, glutation peroxidase and by molecules such as vitamins E, A, C, and K, selenio, cystein and other compounds. Increased OFR levels due to an overproduction of these metabolites or to a failure in the control system, induce cellular and tissue injuries that could lead to diseases such as atherosclerosis, arthritis, fibrosis, lung and heart injuries, neurological disorders and cancer. In this article we consider the use of SOD as therapeutic agents both in human and experimental models. We also refer to the administration of SOD as a protective factor against secondary injuries during radiotherapy and to the determination of SOD as a tumor marker. PMID- 7990692 TI - [Insulin resistance and hypertension: guilty or false clue?]. PMID- 7990693 TI - [Primary biliary cirrhosis and latent distal renal tubular acidosis]. PMID- 7990694 TI - [Latin-American collaborative study on congenital malformations]. PMID- 7990695 TI - [Calculating the number of patients with Chagas disease in Argentina]. PMID- 7990696 TI - Lipids and apolipoproteins in growth hormone-deficient children during treatment. AB - The role of growth hormone (GH) in regulating the transport of plasma lipoproteins has not been clearly defined, but past studies suggest that GH may influence cholesterol levels. This protocol was designed to evaluate possible changes in lipid and apolipoprotein status in GH-deficient children and children with neurosecretory dysfunction (NS) before GH therapy and at intervals after GH therapy was started. Twenty children with classic GH deficiency were evaluated, and 28% were hyperlipidemic at the onset of the study. Seven children were evaluated in the NS group, and only one (14%) showed an elevated total cholesterol (TC) greater than 200 mg/dL. The mean TC for all the GH-deficient children was elevated above the normal range, but not for the NS group. The mean apolipoprotein (apo) C-III level and its heparin-precipitated fraction (HP) were also elevated in the GH-deficient group, but only the apo C-III HP was elevated in the NS group. A standard replacement dose of recombinant methionyl GH was used, and therapy had no significant effect on TC or triglyceride (TG) levels. Apo C-III HP, a marker of hypertriglyceridemia, increased after the start of therapy, but no other lipoprotein levels changed significantly in the GH deficient group. No changes were seen with treatment in the NS group. The longitudinal design of this study allowed demonstration of the later changes in the apolipoproteins and the presence of a distinct subset of patients with both GH deficiency and hypercholesterolemia. This study supports the role of GH in modulating lipid metabolism. PMID- 7990697 TI - Copper deficiency secondary to a copper transport defect: a new copper metabolic disturbance. AB - We describe a 21-year-old man who developed copper deficiency manifested as a demyelinating neuropathy, chronic intestinal pseudo-obstruction, osteoporosis, testicular failure, retinal degeneration, and cardiomyopathy with a tortuous aorta. His serum copper was low and did not increase despite administration of large doses of intravenous copper sulfate. The ceruloplasmin level as measured by an antibody technique was normal, yet ceruloplasmin (Cp) oxidase activity was very low. The Cp amino acid sequence was normal. This suggests that the copper deficiency was caused by a defect in hepatic processing of copper for incorporation into Cp. PMID- 7990698 TI - Increased susceptibility to lipid oxidation of low-density lipoproteins and erythrocyte membranes from diabetic patients. AB - The aim of the present study was to determine if low-density lipoproteins (LDLs) and red blood cell (RBC) membranes from diabetic patients present an increased susceptibility to lipoperoxidation, which might be related to the increased incidence of atherosclerosis in diabetes. LDLs and RBC membranes were isolated from 11 insulin-dependent (IDDM) and 18 non-insulin-dependent diabetic (NIDDM) patients and exposed to a peroxidative stress by incubation with phenylhydrazine. The susceptibility to peroxidation was determined by measuring the production of thiobarbituric acid-reactive substances (TBARS) after the incubation. The following parameters were also evaluated: plasma glucose, triglycerides (TG), phospholipids (PL), total and high-density lipoprotein (HDL) cholesterol, apolipoprotein (apo) A-I, apo B, hemoglobin A1c (HbA1c), LDL PL and cholesterol, LDL fatty acid composition, and RBC membrane PL and cholesterol. Although they were apparently normolipidemic, diabetic patients showed an increased susceptibility to peroxidation in LDLs and erythrocyte membranes as compared with control subjects. The amount of arachidonic acid in LDLs and the PL concentration of RBC membranes from diabetic patients were significantly higher than in normal subjects. The increased lipoperoxidability of both RBC membranes and LDLs might play a central role in the pathogenesis of the vascular complications of diabetes mellitus. PMID- 7990700 TI - Hypocaloric high-protein diet improves glucose oxidation and spares lean body mass: comparison to hypocaloric high-carbohydrate diet. AB - The aim of the study was to investigate the effects of two hypocaloric (800-kcal) diets on body weight reduction and composition, insulin sensitivity, and proteolysis in 25 normal glucose-tolerant obese women. The two diets had the following composition: 45% protein, 35% carbohydrate (CHO), and 20% fat (HP diet, 10 subjects), and 60% CHO, 20% protein, and 20% fat (HC diet, 15 subjects); both lasted 21 days. A euglycemic hyperinsulinemic (25 mU/kg/h) clamp lasting 150 minutes combined with indirect calorimetry was performed before and after the diet. Both diets induced a similar decrease in body weight and fat mass (FM), whereas fat-free mass (FFM) decreased only after the HC diet. 3-Methylhistidine (3-CH3-HIS) excretion was reduced by 48% after the HP diet and remained unchanged after the HC diet (P < .05). A significant correlation was found between the changes in FFM and in 3-CH3-HIS excretion after the diet (rs = .50, P < .02). Blood glucose remained unchanged, while insulin decreased in both diets. Free fatty acids (FFA) significantly increased only after the HC diet (P < .05). During the clamp period, glucose disposal and glucose oxidation significantly increased after the HP diet and significantly decreased after the HC diet. Opposite results were found when measuring lipid oxidation. In conclusion, our experience suggests that (1) a hypocaloric diet providing a high percentage of natural protein can improve insulin sensitivity; and (2) conversely, a hypocaloric high-polysaccharide-CHO diet decreases insulin sensitivity and is unable to spare muscle tissue. PMID- 7990699 TI - Maternal hyperhomocysteinemia: a risk factor for neural-tube defects? AB - The maternal vitamin status, especially of folate, is involved in the pathogenesis of neural-tube defects (NTDs). Maternal folate administration can prevent these malformations. The precise metabolic mechanism of the beneficial effect of folate is unclear. In this study we focus on homocysteine accumulation, which may derive from abnormalities of metabolism of folate, vitamin B12, and vitamin B6. We studied nonpregnant women, 41 of whom had given birth to infants with NTDs and 50 control women who previously had normal offspring. The determinations included the plasma total homocysteine both in the fasting state and 6 hours after the ingestion of a methionine load. In addition, we measured the fasting blood levels of folate, vitamin B12, and vitamin B6. The mean values for both basal homocysteine and homocysteine following a methionine load were significantly increased in the group of women who previously had infants with NTDs. In nine of these subjects and two controls, the values after methionine ingestion exceeded the mean control by more than 2 standard deviations. Cystathionine synthase levels in skin fibroblasts derived from these methionine intolerant women were within the normal range. Our findings suggest a disorder in the remethylation of homocysteine to methionine due to an acquired (ie, nutritional) or inherited derangement of folate or vitamin B12 metabolism. Increased homocysteine levels can be normalized by administration of vitamin B6 or folate. Therefore, we suggest that the prevention of NTDs by periconceptional folate administration may effectively correct a mild to moderate hyperhomocysteinemia. PMID- 7990701 TI - Lactate release and uptake in hepatoma 7288CTC perfused in situ with L-[(U) 14C]lactate or D-[(U)-14C]glucose. AB - Arteriovenous differences (AVD) for glucose and lactic acid measured across tissue-isolated rat tumors in vivo have shown that individual tumors with similar rates of glucose consumption may either release or utilize lactic acid. The experiments described here investigated the relationships among arterial blood lactate concentrations and tumor lactate and glucose balances. AVDs for lactate, pyruvate, glucose, 14CO2, PO2, PCO2, pH, and lactate specific activities were measured across 17 tissue-isolated 7288CTC hepatomas perfused in situ with arterial blood containing 2.5 to 14.4 mmol/L lactate and either L-[(U)-14C]lactic acid or D-[(U)-14C]glucose. Measurements were made over a range of blood flow rates from 60% to 200% of the mean in vivo rate, 0.11 mL/min. Data collected during steady states were compared by regression analysis. Tumor lactate balance and the arterial blood lactate concentration were directly related (r = .895, n = 22, P < .01). Net negative and positive balances occurred below and above approximately 6.5 mmol/L arterial blood lactate, respectively. The mean intratumor lactate concentration for all tumors was 6.9 +/- 1.0 mmol/L (mean +/- SD, n = 13). Rates of 14C-lactate oxidation to 14CO2 (r = .716, n = 18, P < .01) and tumor venous/arterial blood 14C-lactate specific activity ratios (r = .845, n = 19, P < .01) were low during lactate release and were increased during lactate uptake. Total arterial blood lactate removal estimated from chemical and isotopic analyses was 23.1% +/- 11% and 43.0% +/- 16% (P < .05), respectively, for six lactate-utilizing tumors. Perfusions performed with 14C-glucose showed that approximately 50% of the glucose consumed during net negative lactate balance was released as 14C-lactate to the tumor venous blood, whereas only 5% was released as 14C-lactate during net positive lactate balance. The data support the following conclusions: Arterial blood lactate controls net lactate balance in solid tumors; high concentrations increase uptake. Lactate uptake inhibits lactate formation from glucose without changing the glucose balance. Lactate is release during net lactate uptake. Since lactate uptake may exceed glucose uptake, arterial blood lactate can be a substrate for tumor energy metabolism and growth. PMID- 7990702 TI - Plasma cholesteryl ester transfer protein activity in non-insulin-dependent diabetic patients with and without coronary artery disease. AB - The present study was designed to evaluate the potential role of plasma cholesteryl ester transfer protein (CETP) activity in the regulation of high density lipoprotein (HDL) subclasses in non-insulin-dependent diabetes mellitus (NIDDM). We studied 45 men with NIDDM and angiographically defined coronary artery disease ([CAD] DM+CAD+, aged 54.4 +/- 6.1 years, mean +/- SD); 47 nondiabetic men with similarly proven CAD (DM-CAD+, aged 54.9 +/- 6.6 years; 43 men with NIDDM but no CAD (DM+CAD-, aged 55.2 +/- 7.3 years); and 29 nondiabetic men without CAD (DM-CAD-, aged 53.2 +/- 5.3 years). The groups were matched for age and body mass index (BMI). Plasma CETP activity was determined by measuring the ability of the plasma sample to transfer esterified cholesterol from exogenous 14C-cholesteryl ester-labeled low-density lipoprotein (LDL) to exogenous HDL. Plasma lipoproteins were separated by ultracentrifugation. The concentration of HDL cholesterol was reduced in the DM+CAD+ group as compared with the DM-CAD- group (P < .01). This change was due to a decrease of both HDL2 cholesterol (P < .05) and HDL3 cholesterol (P < .001). There was a clear-cut decrease in HDL3 cholesterol in the DM-CAD+ (P < .01) and DM+CAD- (P < .05) groups as compared with the DM-CAD- group. Plasma CETP activity was lower in the DM+CAD- group (1.06 +/- 0.24 arbitrary units [AU]) than in the DM-CAD- group (1.19 +/- 0.26 AU, P < .05). In the DM+CAD+ group, the mean of CETP activities was 1.09 AU.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7990704 TI - The role of glucagon in the control of protein and amino acid metabolism in vivo. AB - The relative contribution of hyperglucagonemia to the mechanisms of nitrogen loss during catabolic states has not been clearly established. The present study examines the independent effect of physiologic elevations of plasma glucagon on whole-body protein kinetics, as well as on net amino acid balance across the liver and gastrointestinal tract tissues, in conscious 18-hour-fasted dogs (n = 7). Each study consisted of a 120-minute equilibration period, a 30-minute basal period, and a 150-minute experimental period. Leucine kinetics were measured using L-[1-14C]leucine. Pancreatic hormones were maintained by infusing intravenous somatostatin (0.8 micrograms/kg.min), intraportal insulin (275 microU/kg.min), and intraportal glucagon (0.65 ng/kg.min basally and 2.5 experimentally). Dextrose was infused to maintain plasma glucose constant (14.1 +/- 0.3 mumol/L), thereby providing a consistent metabolic steady state for the study of protein and amino acid metabolism. In the experimental period, plasma glucagon was fourfold basal levels (112 +/- 10 v 32 +/- 6 pg/mL), whereas plasma insulin remained stable (mean, 10 +/- 1 microU/mL). Hepatic glucose production was increased 30%, but leucine rates of appearance ([Ra] proteolysis), oxidative disappearance (Rd), and nonoxidative Rd (protein synthesis) were not altered during the experimental period. Furthermore, the net release of amino acids by the gastrointestinal tract was not increased by glucagon. However, uptake and extraction of amino acids by the liver were increased, resulting in a 17% decrease in total plasma amino acids.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7990705 TI - Changes in body composition and adipose tissue distribution after treatment of women with Cushing's syndrome. AB - Longitudinal studies on changes in body composition and adipose tissue (AT) distribution in response to altered cortisol exposure have not yet been undertaken. Therefore, we determined body composition in seven women aged 34 +/- 9 years (mean +/- SD) with Cushing's disease/syndrome before and 8 +/- 2 (SD) months after surgical treatment for pituitary (n = 5) or cortical adrenal (n = 2) adenomas. The treatment resulted in a reduction of plasma and urinary cortisol by 78% and 97% (P < .01), respectively, and body weight (BW) reductions of 10.2 +/- 8.1 (SD) kg. The volumes of AT, skeletal muscle plus skin, and visceral organs were determined using a multiscan computed tomography (CT) technique. Organ and tissue volumes were converted to weight by multiplying with organ densities. After treatment, AT was reduced by 8.2 +/- 6.1 kg (P = .012), skeletal muscle plus skin by 1.3 +/- 1.7 kg (NS), and visceral organs by 0.6 +/- 1.0 kg (NS). The net change of AT, skeletal muscle plus skin, and visceral organs (delta AMV) was thus -10.1 +/- 7.8 kg, which was in good agreement with the change in BW (delta BW, -10.2 +/- 8.1 kg). The standard error of a single determination calculated on the differences between delta BW and delta AMV was 2.8%. Although total skeletal muscle plus skin was not changed, muscle of arms was reduced by 0.3 +/- 0.2 L (P = .014). Except for leg AT (P = .088), the reductions of all regional AT depots (arms, head+neck, subcutaneous trunk, viscera) were significant when expressed in liters. The total AT was reduced by 23% +/- 11%.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7990703 TI - Sex differences in the adaptation of glucose metabolism to short-term fasting: effects of oral contraceptives. AB - The adaptation to long-term starvation is different in men and women. To evaluate whether there are also sex differences during short-term fasting (< 24 hours), we studied glucose metabolism after 16 and again after 22 hours of starvation in healthy subjects: six men, six women in both the follicular and luteal phases of their menstrual cycle, and six women on oral contraceptives ([OCC] day 12 of cycle). Glucose oxidation was measured by indirect calorimetry, and hepatic glucose output by infusion of 3-3H-glucose. There were no differences in hepatic glucose output between men and women during short-term fasting. The basal (16 hours) plasma glucose concentration was lower in women on OCC than in men (P < .05). Prolongation of the postabsorptive state induced a similar decline in plasma glucose concentrations in all groups. Basal (16 hours) glucose oxidation was lower in women on OCC than in men (P < .05). Prolongation of the postabsorptive state by 6 hours caused a significant decrease in glucose oxidation only in men. After 22 hours of fasting, glucose oxidation was lower in women on OCC than in women with normal menstrual cycles. In conclusion, the metabolic adaptation to the postabsorptive state (< 24 hours of fasting) is regulated differently in women on OCC as compared with women with normal menstrual cycles and men. These differences preclude inclusion of women on OCC in studies of glucose metabolism in the postabsorptive state. PMID- 7990706 TI - Oxidative-modified and acetylated low-density lipoproteins differ in their effects on cholesterol synthesis and stimulate synthesis of apolipoprotein E in rat peritoneal macrophages by different mechanisms. AB - Apolipoprotein (apo) E plays an important role in the recognition of lipoproteins by cellular lipoprotein receptors. Unlike other apolipoproteins, apo E is expressed by many extrahepatic tissues including macrophages (M phi). Resident M phi express low levels of apo E. However, their synthesis of apo E is substantially increased after M phi have been incubated with acetylated low density lipoprotein (LDL). But acetylation of LDL is not known to occur in vivo. On the other hand, modification of LDL by oxidation and by enzymatic action is believed to happen physiologically. In this report, we compared the effects of various modified LDLs on the synthesis of apo E by M phi. Freshly isolated human LDL was modified by (1) repeated addition of acetic anhydride (Ac-LDL); (2) incubation with 20 mumol/L CuSO4 at 37 degrees C for 24 hours (Ox-LDL); and (3) incubation with phospholipase C at 37 degrees C for 1 hour (PI-LDL). Resident peritoneal M phi were collected by lavage from rats and allowed to attach to plastic culture dishes. Although native LDL had no effect, treatment with Ac-, Ox , and PI-LDL (50 micrograms/mL each) was found to increase medium apo E by ( fold) 4.19 +/- 0.26, 4.20 +/- 0.34, and 2.02 +/- 0.20 (mean +/- SEM, n = 5), respectively, as compared with untreated cells. Northern blot analysis revealed that cellular apo E mRNA was increased in parallel to apo E protein by Ac-LDL and PI-LDL. However, increases of apo E protein and mRNA by Ox-LDL were not equal.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7990707 TI - Cyclic guanosine monophosphate responses to atrial natriuretic factor, brain natriuretic peptide, but not C-type natriuretic peptide, and the characterization of their receptors in rat medullary thick ascending limb. AB - The effects of atrial natriuretic factor (ANF), brain natriuretic peptide (BNP), and C-type natriuretic peptide (CNP) on renal medullary thick ascending limb (mTAL) have not been fully understood. The aim of this study is to examine the second-messenger responses of rat mTAL to ANF, BNP, and CNP. Characterizations of the ANF, BNP, and CNP receptors in mTAL were also performed by radioligand studies. Results showed that ANF and BNP were both capable of eliciting cyclic guanosine monophosphate (cGMP) responses in mTAL. Conversely, no cGMP response was observed upon stimulation by CNP in mTAL. The presence of ANF receptors was demonstrated by radioligand studies. One receptor site was found, and the Kd and maximum binding capacity were 4.0 +/- 0.45 nmol/L and 277.8 +/- 47.7 fmol/mg protein, respectively. BNP receptors were also found in mTAL, and ANF and BNP were sharing the same receptor. On the contrary, no CNP receptor could be shown by radioligand studies. These results suggest that guanylyl cyclase-coupled receptors (atrial natriuretic peptide receptor-A [ANPR-A]) specific for ANF and BNP are present in rat mTAL, while those for CNP (ANPR-B) are absent. ANF and BNP but not CNP act on mTAL to control water excretion. PMID- 7990708 TI - Severe impairment of insulin action in adipocytes from amenorrheic subjects with polycystic ovary syndrome. AB - Adipose tissue was used to characterize the metabolic abnormality of insulin resistance in polycystic ovary syndrome (PCOS). Nine patients with PCOS were studied during a period of amenorrhea and confirmed to be chronically anovulatory by vaginal ultrasound and plasma progesterone measurements. These were compared with six age- and body mass index (BMI)-matched controls (BMI, 27.2 +/- 2.2 in PCOS and 24.7 +/- 2.3 in control subjects). Insulin receptor binding was measured and insulin action was assessed by measuring initial rates of 3-O-methylglucose uptake and by inhibition of lipolysis. The maximum specific insulin receptor binding was 0.62% +/- 0.12% and 1.78% +/- 0.18% per 10-cm2 cell surface (mean +/- SEM) in PCOS and control subjects, respectively (P < .001). Maximum rates of glucose transport were also impaired as compared with controls, with 3-O methylglucose transport being 0.90 +/- 0.15 versus 1.57 +/- 0.28 pmol/10 cm2/5 s, respectively (P < .05). The concentration of insulin required for half-maximal stimulation of glucose uptake was 165 +/- 36 versus 32 +/- 10 pmol in PCOS and control subjects, respectively (P < .05). The maximum percentage lipolysis inhibition (mean +/- SEM) was 9.5% +/- 1.6% in PCOS and 28.3% +/- 7.2% in control patients, respectively (P < .01). These data demonstrate that there are both insulin binding and postreceptor defects in adipocytes from amenorrheic PCOS subjects. The degree of defect in adipocyte insulin action is greater than would have been anticipated from in vivo data. PMID- 7990709 TI - Changes in body composition, resting energy expenditure, and thermic effect of food in short children on growth hormone therapy. AB - The effect of growth hormone (GH) treatment on body composition, resting energy expenditure (REE), and the thermic effect of food (TEF) was studied in 10 prepubertal boys (aged 6.2 to 9.5 years, with subnormal spontaneous GH secretion during the first 6 months of treatment [0.2 IU/kg.dl]). Patients were studied before and at 2, 4, and 6 months after commencing treatment. Height and weight increased significantly during treatment (112.2 +/- 4.5 to 117.2 +/- 6.0 cm and 18.0 +/- 2.8 to 20.8 +/- 3.2 kg, respectively). Body fat percent decreased significantly (15.93% +/- 4.08% to 11.97% +/- 3.30%, P < .0002), but was not different at 4 and 6 months. Total body potassium (TBK) increased significantly (39.15 +/- 5.77 to 48.70 +/- 6.35 g, P < .001) during treatment. When correcting for the expected changes in body composition over time, height and weight were still shown to increase, fat percent decreased significantly, but TBK and mid-arm muscle circumference (MAMC) were not different from the expected values. REE increased significantly during treatment, but when it was expressed per TBK or corrected for the change in kilograms of fat-free body mass (FFBM), it increased only at 2 months and stabilized thereafter. The TEF was increased at 2 and 4 months of treatment and returned to pretreatment levels at 6 months of treatment. Substrate utilization as studied by indirect calorimetry pointed toward a significant protein-sparing effect during the first 4 months of treatment; this change tended to disappear in resting energy metabolism by 6 months of GH treatment.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7990710 TI - Impaired postprandial glucose utilization in non-insulin-dependent diabetes mellitus. AB - The importance of impaired glucose utilization in the pathogenesis of postprandial hyperglycemia in non-insulin-dependent diabetes mellitus (NIDDM) is controversial. Three methods were used to assess glucose utilization following ingestion of a mixed meal in 18 NIDDM and 12 nondiabetic subjects. Dual glucose isotopes were used to determine first-pass splanchnic glucose uptake, suppression of endogenous glucose production, and systemic glucose utilization. Leg balance was used to evaluate skeletal muscle glucose metabolism, and systemic and limb indirect calorimetry were used to assess glucose and lipid oxidation. NIDDM subjects had marked postprandial hyperglycemia as compared with nondiabetics (15.35 +/- 0.72 v 5.83 +/- 0.28 mmol, P < .001), accompanied by lower postprandial insulin (179 +/- 25 v 253 +/- 46 pmol, P < .01) and elevated plasma free fatty acids ([FFA] 569 +/- 34 v 314 +/- 20 mumol/L, P < .001). Cumulative postprandial glucose appearance was nearly twofold greater in NIDDM (82.2 +/- 4.7 v 48.7 +/- 4.9 g.5h, P < .001) due to increased endogenous glucose production (56.4 +/- 4.8 v 24.5 +/- 1.9 g, P < .001), whereas first-pass splanchnic uptake of ingested glucose was normal in NIDDM. Cumulative postprandial glucose utilization in NIDDM, after correction for urinary glucose, was unchanged from postabsorptive rates, a pattern also found for postprandial glucose oxidation. Cumulative leg glucose uptake was somewhat less in NIDDM subjects (123 +/- 18 v 173 +/- 14 mumol/100 mL leg tissue.5 h, P = .06), whereas lactate and alanine net release across the leg were nevertheless twofold greater in NIDDM (P = .04) and accounted for nearly half of the leg glucose metabolism in NIDDM.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7990711 TI - Hyperzincuria in individuals with insulin-dependent diabetes mellitus: concurrent zinc status and the effect of high-dose zinc supplementation. AB - The urinary excretion of zinc in individuals with insulin-dependent diabetes mellitus (IDDM) is approximately doubled. In the absence of a compensatory mechanism, this hyperzincuria should induce a deficient or marginal Zn status. We examined parameters of Zn status in plasma and in blood cells with respect to urinary Zn losses and Zn supplementation. We measured Zn levels in the urine, plasma, and erythrocytes of 14 IDDM subjects and 15 nondiabetics who kept dietary records for 3 consecutive days. Subsequently, six IDDM subjects and seven nondiabetics were supplemented with 50 mg Zn daily for 28 days. We measured the above parameters, as well as mononuclear leukocyte Zn (MNL-Zn) and the plasma subfraction of albumin-bound Zn (alb-Zn). The total plasma Zn-binding capacity was also assessed. Plasma copper and erythrocyte Cu were monitored as indicators of potential Zn toxicity. Individuals with IDDM displayed the expected hyperzincuria, but had normal blood Zn parameters. Zincuria increased by a similar amount in both groups during supplementation, as did the MNL-Zn content. However, erythrocyte Zn (e-Zn) was refractory, so a trend toward lower e-Zn among IDDM subjects persisted during Zn supplementation. Hemoglobin A1c (HbA1c) increased markedly in the Zn-supplemented IDDM group. Despite their chronic hyperzincuria, individuals with IDDM appear not to be Zn-deficient. Large-dose Zn supplementation increases MNL-Zn and induces an undesirable elevation of HbA1c in all individuals. This is especially disconcerting for those with IDDM, and may reflect an exacerbation of a chronic "Zn diabetes." These data suggest a potential for toxicity from large-dose Zn supplementation. PMID- 7990712 TI - Biochemical hyperparathyroidism and bone mineral status in patients treated long term with lithium. AB - Lithium is known to interfere with normal calcium homeostasis, but the long-term effects and possible clinical significance are uncertain. Thus, we measured indices of parathyroid function including intact parathyroid hormone (PTH) and ionized and total calcium levels in 26 patients treated for manic-depressive psychosis with lithium for 10 years or longer (mean +/- SD duration, 15 +/- 6 years). Increased ionized calcium levels were found in 11 patients and increased PTH concentrations in five patients. Altogether, 54% of the patients (14 of 26) had ionized calcium and/or PTH levels above the laboratory reference range. The PTH/ionized calcium relationship of the lithium-treated patients was compared with that of a group of normal subjects (n = 23) and with those of three different groups of patients with abnormal parathyroid function (chronic hypoparathyroidism, n = 21; primary hyperparathyroidism [HPT], n = 50; and tertiary HPT, n = 21). Lithium-treated patients had significantly higher ionized calcium levels (P < .0001) but not significantly higher PTH concentrations (P = .08) than the normal subjects. In comparison to the normal controls, lithium treated patients had a right-sided shift in their PTH/ionized calcium relationship that was in the same direction but less prominent than in primary or tertiary HPT. Dual-energy x-ray absorptiometry disclosed similar bone mineral densities (BMDs) of lithium-treated patients and age-, sex-, and body mass matched normal controls in the whole body, lumbar spine, and femoral neck (Z scores: +1.20, +1.22, and +1.02, respectively.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7990713 TI - Absence of insulin receptor gene mutations in three insulin-resistant women with the polycystic ovary syndrome. AB - Women with polycystic ovary syndrome (PCOS) are markedly insulin-resistant, but the molecular mechanisms of these changes and their relationship to the hyperandrogenic state remain to be clarified. Mutations have recently been identified in the insulin receptor gene of patients with extreme forms of insulin resistance associated with hyperandrogenism (eg, type A insulin resistance), and these mutations account for the insulin resistance in such patients. We performed this study to determine whether mutations in the coding portion of the insulin receptor gene were responsible for insulin resistance in PCOS. Insulin binding studies using cultured skin fibroblasts of three obese (body mass index > 27 kg/m2) women with PCOS (ie, mild hyperandrogenemia and chronic anovulation of unknown etiology) and documented insulin resistance showed no apparent abnormalities in either the number or affinity of insulin binding sites. Direct sequencing of all 22 exons of the insulin receptor gene from two of the women with PCOS did not reveal any mutations. Furthermore, both alleles of the gene were expressed at equal levels. In a third insulin-resistant PCOS woman, there was no evidence for a mutation in the coding portion of the insulin receptor gene as determined by denaturing gradient gel electrophoresis (DGGE). We conclude that the insulin resistance in these PCOS women was caused by a defect extrinsic to the insulin receptor. PMID- 7990714 TI - Folate-mediated incorporation of ring-2-carbon of histidine into nucleic acids: influence of thyroid hormone. AB - Folate-mediated incorporation of [ring-2-14C]histidine into DNA and its modulation under thyroid stress have been studied. Both hyperthyroidism and hypothyroidism decrease the folate-mediated incorporation of the one-carbon unit derived from histidine into DNA significantly, resulting in growth retardation. In concurrence with previous reports, in vivo oxidation of histidine is decreased in hyperthyroidism and increased in hypothyroidism. 5,10 Methylenetetrahydrofolate reductase levels are elevated in hyperthyroidism and decreased in hypothyroidism, whereas methionine synthase levels are decreased in hyperthyroidism and increased in hypothyroidism. It is discussed how in both hyperthyroidism and hypothyroidism folate cofactor-mediated reactions are adversely affected. PMID- 7990715 TI - Hyperinsulinemia predicts low tissue plasminogen activator activity in a healthy population: the Northern Sweden MONICA Study. AB - Fibrinogen levels predict atherothrombotic disease, and impaired fibrinolysis has been proposed as a risk factor for myocardial infarction. Fibrinolysis is mainly dependent on the activity of tissue plasminogen activator (tPA) and its inhibitor plasminogen activator inhibitor type-1 (PAI-1). Oral glucose tolerance tests were performed in 318 randomly selected healthy men and 324 women aged 25 to 64 years. tPA activity was strongly predicted by fasting insulin in both univariate analysis (r = -.37 and -.34 in men and women, respectively) and multivariate analysis with age, anthropometric measurements, lipids, and blood pressure included. Fasting insulin was the strongest predictor of PAI-1 activity (r = .49 and .51). In women, the influence of fasting insulin level on tPA and PAI-1 activity was consistently stronger after than before menopause, and a threshold effect was seen with distinctly lower fibrinolytic activity in the highest quartile of insulin (> 7.0 mU/L). In men, the relation between insulin and fibrinolytic variables was linear. Fibrinogen levels were not related to insulin or glucose levels after adjustment for age and other risk factors in a multiple regression. Subjects with previously unknown diabetes or impaired glucose tolerance tended to have elevated fibrinogen and PAI-1 activity and decreased tPA activity. Our data support previous findings of a strong correlation between insulin and PAI-1 activity in small highly selected groups, and extend them to randomly selected population samples. The strong inverse relation between endogenous insulin levels and tPA activity has not previously been demonstrated in a healthy population. PMID- 7990716 TI - Effect of hemodilution and resuscitation on tumor interstitial fluid pressure, blood flow, and oxygenation. AB - Hemodilution due to hemorrhage may increase tumor blood flow (TBF) by lowering blood viscosity and decrease tumor interstitial fluid pressure (TIFP) by moving fluid from the interstitium to the vascular compartment and by lowering microvascular pressure (MVP), mainly due to the decrease in systemic pressure. To test this hypothesis, we measured mean arterial blood pressure (MABP), TIFP, hematocrit, relative TBF (RBC flux), and intratumor pO2 during hemorrhage and volume restitution in severe combined immunodeficient mice, bearing LS174T human colon adenocarcinoma xenografts. MABP and TIFP significantly decreased after 0.2 ml of blood (approximately 12% of blood volume) was withdrawn. MABP decreased from 87.5 +/- 3.9 mmHg (mean +/- standard error) to 59.8 +/- 4.8 mmHg (n = 5, P = 0.01) within 2.5 min after the withdrawal of blood and then returned to control value within 10 min. TIFP gradually decreased from 18.7 +/- 2.3 mmHg to 11.3 +/- 0.9 mmHg after 1 hr (n = 8, P = 0.01), while RBC flux increased by a factor of 1.99 +/- 0.38 (n = 5, P = 0.02). The systemic hematocrit decreased from 51.2 to 45.9% (n = 7, P = 0.02). Tumor oxygenation did not significantly improve (median pO2 for control, 28 mmHg, and median pO2 after blood withdrawal, 32 mmHg; P = 0.14). When 0.2 ml blood was withdrawn and replaced (within 2.5 min) with the same volume of normal saline, MABP significantly decreased from 86.4 +/- 2.4 mmHg to 65.6 +/- 4.6 mmHg (n = 11) at 1 hr post-treatment (P = 0.001). TIFP decreased, but not significantly, from 24.2 +/- 2.9 mmHg to 20.4 +/- 2.4 mmHg (P = 0.35). Blood withdrawals in excess of 0.3 ml significantly decreased MABP and TIFP without recovery during 1 hr of observation. Volume restitution with hyperoncotic/hyperosmotic 6.0% Dextran 70 and 7.5% saline had effects attributable to a direct transmission of systemic pressure to the tumor microcirculation and to a lowering of tumor venous resistance. These effects appear to be common to saline blood restitution and volume top-load with Dextran 70. In conclusion, mild hemorrhage (withdrawal of approximately 12% of blood volume) can significantly lower TIFP without a reduction in TBF and pO2. PMID- 7990717 TI - Periwound skin microcirculation of venous leg ulcers. AB - Chronic venous ulceration has an estimated prevalence of from 0.06 to 1.3% with about 57 to 80% of patients with leg ulcers having demonstrable venous disease. The sequence of events whereby chronic venous insufficiency leads to leg skin ulceration is not yet worked out. Venous hypertension may set the stage for subsequent ulcer development via linkages to observed changes in skin microvessel metrics, morphology, rheology, permeability, hemodynamics, and the interstitium. Periulcer measurements show decreased transcutaneous oxygen and elevated carbon dioxide tensions, yet the skin blood perfusion measured with laser Doppler fluxometry (LDF) is reported to be elevated. This elevated perfusion, (Q), could be due to independent changes in blood velocity (U), and volume (V), with different mechanistic implications depending on the mode. Thus, we sought to determine the relative contributions of these two components with the aim of clarifying the mechanism responsible for the reported skin flow changes. Patients studied (n = 16) had unilateral venous ulcers, an ankle/brachial BP index > 0.8, and venous pathology demonstrated by duplex imaging. Ulcer areas ranged from 0.6 to 76.9 cm2 (mean = 13.7 cm2) and were present for 2 to 144 months, mean = 32. With the patient supine, Q (ml/min/100 g), V (%), and U (mm/sec) were measured by LDF (Vasamedics, BPM403A) at two to three sites on periulcer skin and compared with measurements at corresponding sites on the nonulcerated limb at local skin temperatures of 35 and 44. Results confirm an elevation in basal periulcer flow (7.0 vs 1.8 ml/min/100 g, P = 0.001) and show this to be due to elevations in both circulating blood volume (1.24 vs 0.62%, P < 0.001) and velocity (1.23 vs 0.65 mm/sec, P = .004). Maximal Q, V, and U were also higher on the ulcer leg, being for Q, 11.2 vs 6.42 ml/min/100 g, P = 0.03; for V, 1.49 vs 1.13%, P = .002; and for U, 1.76 vs 1.33 mm/sec, P = 0.020. Expressing each leg's basal values as a percentage of its own maximal response shows the ulcerated leg to have higher values for Q, V, and U, with (ulcer leg/control leg) ratios being 2.5, 1.8, and 1.4, respectively. These findings show that the LDF perfusion increase is due to roughly equal increases in microvessel circulating blood volume and velocity.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 7990718 TI - Microcirculatory dynamics of neuropeptide Y. AB - We used the hamster cheek pouch microcirculation to investigate by intravital microscopy the effects of neuropeptide Y (NPY) on arteriolar diameter, leukocyte adhesion to microvascular endothelium, and postcapillary venular permeability. We applied NPY topically for 3 min at concentrations of 10(-7), 10(-9), and 10(-11) M. We quantified arteriolar diameter and permeability changes by digital image analysis. We used the mass of fluorescein isothiocyanate-Dextran 150 accumulated around postcapillary venules (10-30 microns) to calculate extravasation rates of macromolecules. We also measured the number of adhering white cells per 100 microns length of postcapillary venules using acridine orange to label white blood cells. At the applied doses, NPY did not alter either microvascular permeability to macromolecules or leukocyte adhesion to microvascular walls. NPY, in a dose-dependent manner, constricted arterioles ranging in control diameter from 10 to 60 microns. Vasoconstriction was strongest in arterioles ranging in diameter from 30 to 39 microns at a concentration of NPY of 10(-7) M. The Y1-type NPY receptor agonist, Leu31, Pro34-NPY, was as potent as NPY, whereas the carboxy terminal fragment NPY 13-36 had no activity, indicating that the hamster cheek pouch microvasculature expresses the Y1 type of NPY receptor. We also blocked alpha-adrenergic receptors to test whether norepinephrine is required for NPY induced vasoconstriction. This blockade did not inhibit the vasoconstriction caused by exogenous NPY. Our results demonstrate that (1) NPY modulates microvascular hemodynamics by changes in arteriolar diameter, (2) the NPY receptor on the hamster cheek pouch microvasculature is of the Y1 type, and (3) exogenous NPY-induced vasoconstriction is independent of the activity of endogenous norepinephrine. PMID- 7990719 TI - Effect of erythrocyte heat treatment on pulmonary vascular resistance. AB - The effect of red blood cell deformability on the pulmonary vascular resistance was studied in isolated dog and rat lungs. Blood cells were incubated at 49 degrees C for 1 hr, to render them rigid. The resistance to blood flow in the lung was assessed either by calculating the pulmonary vascular resistance (PVR = arterial - venous pressure difference divided by flow rate) or by examining the vascular pressure-flow relationship for changes in slope and intercept. The resistance in the lung was first assessed during perfusion with normal blood and again during perfusion with rigid cells. The results showed that PVR in dog lungs increased by 15% during perfusion with heat-treated blood and that this increase in PVR was associated with a significant increase in the middle segment resistance (arterial-venous occlusion technique) and with an increase in critical closing pressure (pressure intercept of the pressure-flow curve). In contrast to the small effect in dog lungs, the PVR in rat lungs rose more than 400% during perfusion with heat-treated blood. The marked increase of PVR in rat lungs was prevented with papaverine (PVR increased only 58%), suggesting that vasoconstriction was a primary event in rat lungs. The rise in vascular resistance in rat lungs was further shown to be primarily due to the presence of rigid erythrocytes (RBC). The increase in PVR in the rat lungs was not due to mechanical obstruction of the vasculature but rather to constriction of arteries and veins (double occlusion technique). The conclusion from this study is that RBC deformability plays an important role in the pulmonary vasculature, primarily because of release of vasoactive substances and partially because of the potential mechanical obstruction of capillaries. These events are apparently species dependent and are attributed mostly to red blood cell deformability which decreases during heat treatment. PMID- 7990720 TI - In situ study of the membrane potential in microvascular endothelial cells using a fluorescent probe. PMID- 7990721 TI - Spatial heterogeneity in normal skin perfusion recorded with laser Doppler imaging and flowmetry. AB - Spatial and temporal variations in forearm skin perfusion captured by laser Doppler perfusion imaging (LDI) have been compared with topographic maps recorded by laser Doppler flowmetry. In order to determine the shortest LDI sampling time required at each measurement site, with an adequate signal-to-noise ratio and with the ability to display the heterogeneity in skin perfusion, the noise limited resolution of the LDI system as well as various sampling times were tested. The noise-limited resolution for medium and high light intensities were less than 0.5% (temporal) and 0.3% (spatial) of full scale. A sampling time of 1 sec was selected and image presentation was made by performing bilinear interpolation between perfusion values. The same area (10 x 10 mm) was mapped with LDI and topographic mapping at seven different sites. In addition, a larger area covering the surrounding skin was recorded with LDI. The small area recordings with LDI and topographic mapping could be identified in the larger LDI image. High-and low-perfusion spots coincided between the two systems. Temporal variations were studied by repeated LDI recordings of the same areas as above. Small spots were selected in the areas and plotted versus time. Without provocation, the total perfusion changes at each spot showed large variations, but the relative perfusion levels between neighboring spots persisted. Provocation with heat increased the perfusion in all spots. PMID- 7990722 TI - A novel method to assess reactivities of retinal microcirculation. AB - This study introduces a novel method of bovine retinal microcirculation preparation to assess reactivities of retinal microvessels in ex vivo. This preparation is perfused intraluminally through the retinal artery. Effects of vasoactive hormones on these microvessels can be studied by perfusion or topical application to muscle bath. Effects of these compounds on the retinal microvessels of 1A (180- to 200-microns diameters), 2A (50- to 60-microns diameter), and 3A (20- to 30-microns diameter) can be assessed simultaneously using video microscopy. In this study, the water-soluble compound endothelin-1, when applied topically, caused dose-dependent vasoconstriction of all microvessels but had no effect when perfused intraluminally. On the other hand, lipid-soluble prostaglandin F2 alpha (PGF alpha) caused dose-dependent vasoconstriction when administered either intra- or extraluminally. Furthermore, preconstricted retinal arterioles (by PGF alpha) were dilated in a dose-dependent manner when acetylcholine was perfused through the retinal artery. This vasodilation was attenuated by atropine or N3-monomethyl arginine, a nitric oxide synthase inhibitor. Topical potassium chloride also caused dose-dependent vasoconstriction of all retinal microvessels. Fluorescein angiography showed no breakdown of the blood-retinal barrier. Thus, in this ex vivo perfused bovine retinal microcirculation preparation, the water-soluble compounds may not cross the blood-retinal barrier to affect microcirculation while lipid soluble can affect this circulation. Additionally this study shows that endothelial-derived compounds, endothelin and nitric oxide, caused vasoconstriction and dilation, respectively. PMID- 7990725 TI - Delayed recovery of endothelium-dependent vasodilation in regenerating arterioles of skeletal muscle autografts. AB - This study investigated the responses of regenerating arterioles in grafted skeletal muscle to the endothelium-dependent dilator acetylcholine (ACh); the substrate for endothelium-derived relaxing factor (EDRF), L-arginine (L-Arg); and sodium nitroprusside (SNP). Additionally, responses of graft arterioles to the endothelium-independent substances adenosine (Ado) and norepinephrine (NE) were measured. The retractor muscle of hamsters was removed, placed in a myotoxic solution, and grafted into its original site. The graft revascularized spontaneously by sprouting of vessels in surrounding tissue. Quantification of changes in arteriolar luminal diameter was accomplished using in vivo video microscopy at 30, 45, and 60 days postgrafting. In 30-day grafts, there was little or no response to topically applied ACh or L-Arg. By 45 days, arteriole response to 10(-6), 10(-5), and 10(-4) M ACh and 10(-4) L-Arg was 0, 4, 20, and 17% of the control response, respectively. SNP (10(-6)-10(-4) M) produced approximately 50% of the control response at both 30 and 45 days. By 60 days the response of graft arterioles to ACh, L-Arg, and SNP was not different from controls. Arteriolar response in 30-day grafts to Ado (10(-6)-10(-4) M) was significantly attenuated, but was not different from control by 45 days. Responsiveness of arterioles to NE had recovered to control levels by 30 days postgrafting. These data indicate that the restoration of endothelium-dependent regulation of arteriolar dilation lags behind endothelium-independent, receptor mediated mechanisms. The diminished response of regenerating arterioles may be related to dysfunctions in both the synthetic pathway for EDRF and the guanylate cyclase/cGMP mechanism for vascular smooth muscle cell relaxation and/or flow dependent mechanisms of blood flow regulation. PMID- 7990726 TI - Antitrust laws/the State Action Immunity Doctrine. PMID- 7990723 TI - Spatial relationships between neuromuscular junctions and microvessels in hamster cremaster muscle. AB - Acetylcholine (ACh) dilates arterioles in skeletal muscle. Neuromuscular junctions (NMJs) are the known source of ACh in this tissue. We hypothesized that microvascular topology is related to the distribution of NMJs. To test this, the spatial relationships between NMJs, arterioles, and capillaries in the hamster cremaster muscle were investigated. Male hamsters (n = 5, 80-100 g) were anesthetized (sodium pentobarbital, 60 mg/kg) and the cremaster was perfused with fluorescein isothiocyanate-bovine serum albumin (FITC-BSA) and Microfil compound. Excised muscles were stained for NMJs (cholinesterase reaction) and cleared in glycerin. Grid overlays divided each cremaster evenly into proximal and distal regions and 40 numbered 3 x 3-mm study fields. Five fields/region (approximately 25% of muscle area) were chosen randomly. Point counting ("counts") on a coherent test grid (component grid dimensions at x 144 magnification: 150 x 150, 300 x 300, and 450 x 450 microns) quantified NMJs, arterioles, and capillaries, respectively. NMJ:arteriole and NMJ:capillary nearest distances were obtained and arterioles nearest NMJs were classified by branch order. Filling with FITC-BSA vs Microfil indicated that all arterioles and approximately 92% of capillaries were perfused with Microfil. Relative counts (i.e., volume fractions) for capillaries were five- to sixfold greater than those for arterioles, which were two- to fivefold greater than those for NMJs. Capillary counts were similar between muscle regions and did not correlate with NMJ counts. In the distal muscle, arteriole and NMJ counts were correlated (r = 0.55, P < 0.05) and counts for both structures were greater than those in proximal regions. NMJ:capillary distances (proximal, 11.9 +/- 0.9 microns; distal, 14.5 +/- 0.6 microns) were less (P < 0.05) than respective NMJ:arteriole distances (111.1 +/- 7.1 and 89.8 +/- 3.2 microns). Fourth- and fifth-order arterioles accounted for 69% of arterioles nearest NMJs. These findings suggest that NMJs may provide a vasoactive stimulus which varies with muscle region and with location in the microvascular network. PMID- 7990724 TI - Effects of L-NMMA and indomethacin on arteriolar vasomotion in skeletal muscle microcirculation of conscious and anesthetized hamsters. AB - The purpose of this study was to determine the influence of NG-monomethyl-L arginine (L-NMMA) and indomethacin (INDO), respectively inhibitors of nitric oxide synthase and cyclooxygenase, on spontaneous arteriolar activity (vasomotion) in the skeletal muscle of awake and anesthetized hamsters. Unanesthetized hamsters, implemented with the skin fold chamber window, displayed vasomotion, whose frequency and amplitude were quantified by power spectrum analysis. Intravenous administration of L-NMMA significantly increased vasomotion frequency and did not change the amplitude at the lower dose, but in order 3 arterioles amplitude decreased significantly. With higher doses L-NMMA caused constriction of order 1-2 vessels, frequency decreased and amplitude increased, and the arteriolar vasodilator response to acetylcholine decreased significantly. During anesthesia topically applied L-NMMA significantly decreased diameter and caused the appearance of vasomotion in order 1-2 arterioles. INDO did not affect vasomotion in unanesthetized hamsters and did not initiate vasomotion during anesthesia leading to the conclusion that prostaglandins do not regulate vasomotion. Vasomotion is not directly related to nitric oxide (NO) in conscious animals while NO blockage stimulates vasomotion in smaller arterioles of anesthetized hamsters without vasomotion; however, the simultaneous inhibition of cyclooxygenase and NO had no effect on arteriolar diameter during anesthesia. It is concluded that vasomotion is regulated by a mechanism that modulates smooth muscle cell activity through the endothelium. PMID- 7990727 TI - George Royer, MD. "Turning cancer kids loose". PMID- 7990728 TI - MSMS task force tackles third party payer problems. PMID- 7990729 TI - MSMS task force identifies priorities with third party payers. PMID- 7990730 TI - Medicare carrier transition update. PMID- 7990731 TI - Outcomes measurement. It's a concept physicians need to understand. AB - "The intricate machinery of our health care system can no longer grasp the threads of experience. The mischief that began long before the health care crisis of the 1970s is progressively disabling the vast machinery of medicine. Too often, payers, physicians, and health care executives do not share common insights into the life of the patient. We acknowledge that our common interest is the patient, but we represent that interest from such divergent, even conflicting, viewpoints that everyone loses perspective. As a result, the health care system has become an organism guided by misguided choices; it is unstable, confused, and desperately in need of a central nervous system that can help it cope with the complexities of modern medicine. The problem is our inability to measure and understand the effect of the choices of patients, payers, and physicians on the patient's aspirations for a better quality of life. The result is that we have uninformed patients, skeptical payers, frustrated physicians, and besieged health care executives." PMID- 7990732 TI - [Effect of antiseptics and redox-cycling agents on Corynebacterium ammoniagenes and related microorganisms in relation to synthesis of a new macroergic compound]. AB - Sublethal concentration of the antiseptic composition Desoxon-1 was shown to provoke in cells of Corinebacterium ammoniagenes in a liquid medium the biosynthesis and accumulation of a novel macroergic 2-methylbutane-1,2,3,4 tetraol-2,4-cyclopyrophosphate. This substance is also synthesized when C. ammoniagenes is cultivated in a solid agar medium supplemented with benzylviologen. Cells preloaded with the new cyclopyrophosphate maintain its content when treated with 4% phenol, DP-2, Desoxon-1 or boiled and heated in an autoclave. Experiments with Mycobacterium tuberculosis and BCG revealed the ability of these bacteria to grow in a medium supplemented with BV++ possibly due to ability of synthesis of a new cyclopyrophosphate which was shown to correlate with resistance toward redox-cycling drugs. Accumulation of polyphosphates in the control cells of M. tuberculosis was illustrated by 31P-NMR spectroscopy and disappearance of the polyphosphates during cultivation in a BV(++)-supplemented medium. No signal of the new cyclopyrophosphate was yet registered in cells of M. tuberculosis by 31P-NMR. PMID- 7990733 TI - [Effect of over-synthesis of cloned gene products on methanol metabolism in the recombinant methylotrophic yeast Hansenula polymorpha]. AB - As is shown expression homologous (dihydroxyacetone kinase) and heterologous (HBsAg, beta-galactosidase) genes in methylotrophic yeasts Hansenula polymorpha DL1 negatively affects on the growth parameters of a host strain. The reducing of specific growth rate (mu max) and yield of biomass per the unit of a consumed substrate (Yx/s) were found in all recombinant strains grown on methanol. Overproduction of dihydroxyacetone kinase and beta-galactosidase in recombinant H. polymorpha was accompanied by two-fold increasing of the activity of alcohol oxidase, which is the first enzyme of methanol oxidation. Otherwise, the activity of formaldehyde dehydrogenase two-fold decreased in the recombinant strain overproducing HBsAg compared with the host strain. It is suggested that the over synthesis of foreign proteins requiring an additional energetic and metabolic expenses might reduce the growth parameters and the activities of some enzymes of methanol metabolism in recombinant methylotrophic yeast H. polymorpha. PMID- 7990734 TI - [Mechanism of specific chromogenic reaction by Klebsiella spp. on nutrient medium with 5-aminosalicylic acid]. AB - The nature of the factor and the mechanism of color reaction with 5 aminosalicylic acid (5-ASA) inherent in bacteria of the genus Klebsiella were investigated. The color reaction was shown to proceed in two stages. During the first stage, occurring in aerobic and anaerobic conditions, the tested strains of Klebsiella decarboxylize 5-ASA yielding CO2 and p-aminophenol, which is a colorless product. During the next strictly aerobic stage which proceeds without participation of bacteria or their exoenzymes, p-aminophenol is oxidized by the air oxygen forming the dark-brown polymers. The color reaction shows high substrate specificity. It is suggested that the color reaction is realized by a previously unknown lyase-type enzyme 5-aminosalicylate decarboxylase (5 aminosalicylate-carboxy-lyase) localized inside the Klebsiella cells. PMID- 7990735 TI - [Cellular ultrastructure of various species of the genus Bifidobacterium]. AB - Morphologic heterogeneity of cells from developing populations of bifidobacteria correlates with ultrastructure peculiarities. Active proliferating cells in exponential phase are characterized by formation of intracytoplasmatic membrane complex represented by lamellar, myelinoform, vesicular structures. Nucleoid is localized as the central polybranched or disperse osmophobic zone. Nucleoid distribution is determined by morphogenesis processes--exobudding, branching or multiseptation. Electronograms reveal multiple polyphosphate and polysaccharide inclusions. Ageing of bifidobacterial populations is accompanied with ultrastructural changes: cell wall hypersynthesis, reorganization and increased size of intracytoplasmatic membrane complex, altered morphology and compactness of nuclei, formation and dissimilation of inclusions. PMID- 7990737 TI - Parkinson's disease: a chronic, low-grade antioxidant deficiency? AB - The cause of Parkinson's disease (PD) is aggressively being pursued. Several hypotheses have been advanced, yet none of these completely explains the large body of evidence research has already uncovered. A new hypothesis, that PD is caused by a chronic antioxidant deficiency state, is outlined in this article. Oxidative stress, mitochondrial abnormalities, epidemiology, genetics, toxins, history of PD and diet are discussed. PMID- 7990736 TI - The fetal antigen hypothesis for breast cancer, revisited. AB - The fetal antigen hypothesis was proposed over a decade ago to explain the small, short-term promotional effect, as well as part of the long-term protective effect that pregnancy has on breast cancer risk. The hypothesis is based on immune interaction between mother and fetus, and postulates that breast cancer genes which a women's fetus inherits from her mate may be indirectly involved in protecting the woman against breast cancer. This article addresses new epidemiological data pertaining to the hypothesis plus the growing evidence that prenatal reproductive factors are important determinants of breast cancer risk. It also suggests that iso-immunization from pregnancy, similar to Rh iso immunization, can produce immunity against breast cancer. The proposed mechanism provides a plan for development of a vaccine against breast cancer. If the fetal antigen hypothesis is valid for breast cancer, the mechanism behind it is likely to apply to other cancers, even cancers that are found in males, since males can be affected be the prenatal component of this mechanism. PMID- 7990738 TI - Gingival hyperplasia induced by calcium channel blockers: mode of action. AB - Gingival hyperplasia is a known side effect in patients treated with diphenylhydantoin, cyclosporin and the calcium channel antagonists. The present study proposes a mechanism by which calcium channel antagonists may induce gingival hyperplasia. The calcium antagonist induces blockage of the aldosterone synthesis in zona glomerulosa of the adrenal cortex since this pathway is calcium dependent, cyclic nucleotide-independent. This may produce a feedback stimulation of an increase in pituitary secretion of ACTH which affects zona glomerulosa hyperplasia. This hyperplasia is merely related by accumulation of steroid intermediate products (androgens) that are transformed to testosterone because of an increase in 17-alpha-hydroxylase enzyme activity. Elevated levels of testosterone may act on the gingival cells and matrix to produce gingival hyperplasia. PMID- 7990739 TI - Pairing modes between homologous chromatids in mammalian spermatogonia. AB - This note comments on a mechanism for pairing homologous chromatids. Of interest are two modes: Ortho and Para. Although both yielding antihelical duplexes, the two modes are not equivalent regarding cladistic relations between homologs. PMID- 7990740 TI - Deep magnetic brain stimulation--the end of psychiatric electroshock therapy? AB - The biophysical processes during electroconvulsive therapy (ECT) are discussed. The multilayer head structure causes a shunting and spreading of the major portions of the current all over the extracranial tissues. The final effect is that only a small percentage of the injected current passes into the brain. The second 'side effect' of the ECT is the electrical overstimulation of the cortex layer, with self-sustained after-discharge causing convulsive seizure. Therefore, the stimulus transmission into the neurochemically and physiologically disturbed meso-diencephalic region is the most important problem. The stimulation of the brain with rapid-rate time-varying magnetic field pulses makes this problem soluble. The magnetic field passes through all head structures with no attenuation and can stimulate the brain without discomfort. Our calculations of stimulus parameters have assumed that this inductive method may be able to evoke the same therapeutic effects as ECT, but in a safer way (painless, noninvasive and without motor seizure). PMID- 7990742 TI - Neural network in the transcription-translation process. AB - The transcription-translation process is represented by a virtual neural network. The input unit corresponds to the transcription process, the hidden unit to the mRNA-ribosome-tRNA interaction and the output unit to the final state of the protein. A correlation was found between the natural amino acid frequency and the degree of codon degeneracy and an inverse correlation between the code degeneracy and the number of amino acid substitutions in the protein. PMID- 7990741 TI - Eosinophils and AIDS. AB - Since early descriptions of Acquired Immune Deficiency Syndrome (AIDS) in the 1980s most of our research effort has been focused on a singular population, the CD4 cell population. Numerous investigations have been done into why there is a gradual diminution in CD4 counts; therapeutic interventions have focused on raising abnormally low CD4 levels. I suggest that another cell line, the eosinophil cell line, may also be abnormal in AIDS and hypothesize that an increase in eosinophil cell count and activation of eosinophils may also be important to AIDS. PMID- 7990743 TI - Can superantigens trigger sudden infant death? AB - A majority of sudden infant death syndrome (SIDS) victims have respiratory or gastrointestinal infections prior to death. This has led to an investigation of the role of pathogenic bacteria and the potentially lethal toxins they produce as triggers for sudden infant death. A small group of bacteria have been consistently identified in SIDS victims as compared to controls, and remarkably, three of these produce superantigenic toxins. Superantigens exert a powerful effect on the immune system, stimulating T-cells, which subsequently induces the formation of large amounts of cytokines. Generation of an overwhelming inflammatory response may lead to death by shock, or other, as yet unrecognized effects of the toxin on the respiratory or cardiac systems. A SIDS/superantigen model is proposed which may explain many of the pathological characteristics of SIDS and establish quantifiable markers for SIDS. PMID- 7990744 TI - The axio-somatic model in embryonic and tumoral development. AB - The growth and evolution of human tissues observed in embryogenesis and neoplasia are both reduced to a cellular theoretical axio-somatic model. The unlimited expansion and phenotype change of the model, are assured by the continuous generation of new cellular mitotic phenotypes which are grafted in a sequential order. Neogeneration results from the interaction between two cells of specific origins and situations: (a) axial cells of actual germ cell origin, generators and vectors of mitotic potential, (b) mitotically exhausted somatic cells of distal phenotypes, involved in meiotic recombinations, generating potential of neodifferentiation. The potentialities of both, axis and soma, are transformed by 'fertilization' in effectively growing new mitotic phenotypes. Bi-potent differentiation of germ line derived cells in gametopoiesis and haematopoiesis, is the source of the axial phenotype, identified in tissues as specific acid fast 'lymphoid' cells and/or vectors, formed by highly condensed hyperchromatinic nuclei and/or micronuclei endowed with DNAs of centromeric and kinetochoric types, wrapped in ceramide rich photo-affinity biomembranes. PMID- 7990745 TI - Cancer: a statistical relationship with road accident deaths and driving. AB - Findings based on a number of statistical studies indicate that road accident deaths (RAD) are a significant measure of vehicular usage. All forms of cancer have highly significant relationships with RAD for males and females, indicating a possible common cause. Circulatory complaints also show the same highly significant correlation. The relationship between cerebrovascular disease (CV) and total cancer (TC), is discussed for Australia, the USA and France, for both males and females, by age group. Indications are that fibrin (as a result of the reduction in coagulation time while driving) might be a factor involved in causation of all cancers. PMID- 7990746 TI - The new method of special brain points stimulation. AB - The integrative function of the subcortical brain structures in higher animals, realized partially via points of reinforcement and avoidance present in hypothalamic nuclei or via the hypothalamo-hypophysial system, suggest the special role these points play in the general and specific schemes of regulation of the nerve system. Stimulation of these points probably affects the brain structures by causing certain ascending effects, thus affects the animal's behavior during self-stimulation. The experimental approach described below is based on the brain itself as the stimulation source, thus allowing the investigation of an oriented effect on the hypothalamus on a similar source. PMID- 7990747 TI - [World Cardiology Congress in Berlin]. PMID- 7990748 TI - [Ear infections]. PMID- 7990749 TI - [Inflammatory diseases of the nose and paranasal sinuses in childhood]. PMID- 7990750 TI - [Adjuvant respiratory tract therapeutic agents. Therapeutic effectiveness]. PMID- 7990751 TI - [Rhino- and coronaviruses. Important pathogens of the common cold]. PMID- 7990752 TI - [What is the difference between organic and inorganic selenium preparations?]. PMID- 7990753 TI - Yohimbine for male sexual dysfunction. PMID- 7990754 TI - Treatment of hypothermia. PMID- 7990755 TI - Cysteamine for cystinosis. PMID- 7990756 TI - Juvenile chronic myelocytic leukemia--report of 10 cases. AB - Ten children (five boys and five girls) with juvenile chronic myelocytic leukemia were seen over a period of 12 years (1980-1991) at the All India Institute of Medical Sciences, New Delhi. With the exception of one who was aged 4.5 years, all children were below 4 years of age (mean age 20.4 months). The presenting features included fever, bleeding secondary to thrombocytopenia, marked hepatosplenomegaly, and skin rash. The striking hematological features were anemia, thrombocytopenia, peripheral blood monocytosis, and normoblastemia. There was no significant myeloid proliferation in the bone marrow aspirate (mean M:E = 5:1), while erythroid proliferation was prominent along with monocytosis (mean 11.2%). Fetal hemoglobin was raised in 8 of the 10 patients (mean 14.1%). Long term survival was poor, with maximum survival being 18 months in one case. New modalities of management of this rare entity are discussed. PMID- 7990757 TI - Recommendations of the Brain Tumor Subcommittee for the reporting of trials. SIOP Brain Tumor Subcommittee. International Society of Pediatric Oncology. AB - Since its constitution during the 22nd annual meeting of the International Society of Pediatric Oncology in Rome in 1990, the Brain Tumor Subcommittee has worked to arrive at a consensus for reporting criteria that should be adopted when brain tumor trials are presented. This consensus is presented here concerning minimum requirements for diagnostic procedures and a systematic approach to define the extent of surgically achieved resection by a radiodiagnostic classification aided by the surgical report as well as response and remission criteria. PMID- 7990758 TI - Cystic adrenal neuroblastoma: prenatal diagnosis by ultrasonography. PMID- 7990759 TI - Increased renal parenchymal echogenicity in ifosfamide-induced renal Fanconi syndrome. AB - Three children who presented with a Fanconi syndrome induced by the chemotherapeutic drug ifosfamide were found to have renal abnormalities on sonogram examinations. Renal echographic changes consisted in hyperechogenicity of the parenchyma with good corticomedullar differentiation. After discontinuation of the chemotherapy, the serum and urine metabolic abnormalities due to proximal tubulopathy were completely or greatly improved. Imaging studies at that time showed a complete resolution of the renal hyperechogenicity. We suggest that in patients exposed to ifosfamide, renal sonogram may be of value to monitor the tubular toxicity of this drug. In these patients, urine and serum monitoring as well as prospective echographic follow-up kidney abnormalities may lead to earlier detection of ifosfamide-induced Fanconi syndrome as well as earlier detection of disease reversibility. PMID- 7990760 TI - Papillary thyroid cancer with pulmonary metastases beginning in childhood: clinical course over three decades. AB - We present a case of childhood papillary thyroid cancer with persistent but stable pulmonary metastases for over three decades in order to highlight the natural history and clinical features of this unusual disease entity. A nine-year old girl had thyroidectomy and cervical lymph node dissection followed by neck irradiation for invasive papillary thyroid cancer. Diffuse pulmonary metastases were present at the time of diagnosis and were treated with radioactive iodine 10 and 30 years later; both the chest radiographs and the patient remained stable throughout. This case illustrates the potential indolence of thyroid cancer when it presents during childhood. PMID- 7990761 TI - Carcinoma of the male breast: update 1994. AB - In many ways, male and female breast cancers are similar, but do have some notable differences. Although the underlying etiology of male breast cancer may be partially due to hormonal or environmental changes, this disease is rare compared to female breast cancer. Most often, it presents as a painless lump, with estrogen receptor-positive infiltrating ductal carcinoma being the most common pathologic type. The main component of local therapy is either a radical or a modified radical mastectomy, with adjuvant chemotherapy proving useful. Estrogen receptor-positive tumors respond well to hormonal therapy. More research is needed in order to: (1) further characterize the molecular biological properties of male breast cancer tumors, (2) further investigate the role of adjuvant chemotherapy, and define successful regimens, and (3) determine optimal chemotherapy regimens in the treatment of metastatic disease. As this disease is a relatively rare condition, whenever possible, all patients should be allowed to participate in national cooperative group studies. PMID- 7990762 TI - Rhabdoid tumor of the kidney with humoral hypercalcemia and parathyroid hormone related protein production. AB - This is a report of a 7-month-old infant with malignant rhabdoid tumor of the kidney (RTK). The patient (pt) demonstrated clinical and biochemical evidence of humoral hypercalcemia of malignancy (HHM). The hypercalcemia responded promptly to calcitonin treatment and tumor removal. Despite aggressive surgery and chemotherapy, the patient expired four months after diagnosis. The primary tumor displayed adenylate cyclase-stimulating activity (ACSA) indicating the production of parathyroid hormone-related protein (PTHrP) by the primary tumor. This is the first report of ACSA documented in a pt with RTK. PMID- 7990764 TI - "Thoughts from SIOP 1993: randomised trials of bone marrow transplantation in paediatric malignancy?" International Society of Pediatric Oncology. PMID- 7990765 TI - Increased risk of cardiac dysfunction after anthracyclines in girls. PMID- 7990763 TI - Acute urticaria and hepatitis complicating high-dose methotrexate therapy. AB - We report an unusual case of anaphylaxis and hepatitic dysfunction in a child with the administration of the twenty-third course of high-dose methotrexate. The latter had been used as an adjuvant to prevent pulmonary metastases and the prior 22 courses had been well tolerated. An attempt to reinstate methotrexate after the twenty-third course was again followed by a similar reaction. PMID- 7990766 TI - Relapse after first cessation of therapy in childhood acute lymphoblastic leukemia: a 10-year follow-up study. Italian Association of Pediatric Hematology Oncology (AIEOP). AB - The outcome of 171 children with ALL who relapsed for the first time after elective cessation of therapy (1-86 mo) and followed over 10 years (median 60 mo; range 1-232 mo) has been evaluated. One hundred and three patients relapsed in the bone marrow (BM), 29 in the testis (T), 21 in the central nervous system (CNS), 14 in the BM plus another site and 4 in other sites. Second remission was achieved in 97% of patients (97% BM, 100% T, 90% CNS, respectively) with reinduction schedules including three or more drugs. All but 4 out of 100 patients who relapsed in the BM received cranial reprophylaxis with intrathecal CT alone or CT plus radiotherapy. Seven patients in second CR underwent allogeneic bone marrow transplantation from an HLA matched sibling. The overall survival was 34% and disease-free survival (DFS) probability at 100 years was 22%. A second relapse was observed in 73% of patients. Forty children are alive in second continuous remission and 24 are alive after a second or subsequent relapse. Patients with isolated T relapse showed a significant better outcome than those with BM or CNS involvement. Most patients (62%) with isolated BM relapse showed a further disease recurrence in BM, and DFS was shorter when relapse occurred within 12 months from off-therapy. Eighty-two patients in second CR stopped the treatment a second time and showed a survival and DFS probabilities, respectively, of 69% and 43%. Thus, children with ALL who relapse after cessation of therapy still have a high risk of further late relapses and should be treated with intensive chemotherapy and CNS reprophylaxis. BMT must be considered for all patients relapsing in the BM within 12 months from off therapy. PMID- 7990767 TI - Intrauterine monoclonal origin of neonatal concordant acute lymphoblastic leukemia in monozygotic twins. AB - We report detailed immunological, cytogenetic and molecular evidence for complete identity of the leukemic cell populations in monozygotic female twins with concordant leukemia diagnosed at two months of age. Both infants had early pre-B acute lymphoblastic leukemia with the (11;19)(q23;p13) chromosomal translocation. A common clonal origin of leukemia in these infants was suggested by the finding of identical oligoclonal heavy chain immunoglobulin gene rearrangements. Leukemic cell DNA was examined for 11q23 rearrangements by Southern blotting and restriction fragments of identical size were found in the two cases, in contrast to the diversity of rearrangements observed in other unrelated and nontwinned control infants with t(11;19)(q23;p13). Similar restriction fragments were absent in blood mononuclear DNA from both parents, liver tissue from one twin and remission bone marrow of the other, indicating that the 11q23 rearrangement was acquired and not inherited as a chromosomal abnormality or polymorphism. These findings provide a definitive evidence for intrauterine single cell origin, with twin to twin transmission, of concordant leukemia in this infant twin pair. PMID- 7990768 TI - In situ breast carcinoma after treatment during adolescence for thyroid cancer with radioiodine. AB - We reviewed the courses of patients treated during childhood or adolescence for thyroid cancer to estimate the frequency of, and to identify possible risk factors for, the occurrence of second malignant tumors in this population. We identified all patients treated for thyroid cancer in a cohort of 1,406 pediatric cancer patients who were diagnosed prior to 20 years of age during the period January 1, 1960 through December 31, 1988 and who were treated at Roswell Park Cancer Institute. Twelve patients were treated for thyroid cancer, of whom nine were women. In situ breast carcinoma was diagnosed 25 and 26 years after diagnosis of thyroid cancer in two of four women treated with radioiodine. No new cancers were diagnosed in the five women treated with thyroidectomy only. Two of four women treated for thyroid cancer during adolescence with radioiodine, which is concentrated in the breast as well as other organs, developed in situ breast carcinoma. Review of a large cohort of adolescent female thyroid cancer patients treated with radioiodine is necessary to provide an accurate estimate of their risk of developing breast cancer. These patients must remain under medical surveillance throughout their lifetimes to facilitate prompt diagnosis of and early intervention for new conditions, such as the occurrence of breast cancer. PMID- 7990769 TI - Treatment of osteosarcoma with ifosfamide: comparison of response in pediatric patients with recurrent disease versus patients previously untreated: a Pediatric Oncology Group study. AB - This study was designed to test if the activity of a phase II agent, ifosfamide, would have been underestimated if it was tested exclusively in a population of children and young adults with recurrent osteosarcoma. The response rate to ifosfamide was compared in patients younger than 30 years of age with previously untreated osteosarcoma with metastases at diagnosis and/or unresectable primary tumors (stratum 1) with that of patients with recurrent osteosarcoma following adjuvant chemotherapy who were not previously exposed to ifosfamide (stratum 2). Evaluation of response was conducted 3 weeks after two courses of ifosfamide (2400 mg/m2 x 5 days) were administered 3 weeks apart. Nine of 33 (27%) evaluable patients in stratum 1 responded (1 complete and 8 partial responses) to ifosfamide. Among 30 evaluable patients in stratum 2, only 3 (10%) responded (1 complete and 2 partial responses; P = .04) Both groups of patients received equal doses of ifosfamide and experienced comparable toxicities. Results from this study suggest that the activity of new agents will be underestimated if tested in a population of heavily pretreated patients with recurrent disease. When possible, new chemotherapeutic agents should be tested in patients with a poor prognosis who have not been exposed to chemotherapy. PMID- 7990770 TI - Wilms' tumor: a rational use of preoperative imaging. AB - OBJECTIVE: To determine whether a preoperative imaging protocol relying predominantly on a chest X-ray film (CXR) and ultrasound in patients with Wilms' tumor is adequate for patient management and to determine the frequency more sophisticated imaging, in particular, computed tomography (CT), is required. DESIGN AND SETTING: Historical cohort study at a tertiary pediatric hospital. SUBJECTS: 60 consecutive patients with Wilms' tumor treated at our institution between 1980 and 1990. MAIN OUTCOME MEASURE: The preoperative imaging was recorded and 2- and 4-year survival were compared with the National Wilms' Tumor Study. RESULTS: 100% of patients had a preoperative CXR, 95% abdominal ultrasound, 5% abdominal CT, 13% chest CT, 47% abdominal X-ray, 2% aortography, 5% cavography, and 35% intravenous urography. The overall 2- and 4-year survivals of 92% and 90%, respectively, did not statistically differ from the National Wilms' Tumor Study 2- and 4-year survivals of 94% and 91%. CONCLUSIONS: A preoperative imaging protocol relying predominantly on a CXR and abdominal ultrasound does not reduce survival. Other more sophisticated imaging, in particular, CT, is not required in the majority of cases and is warranted only when a CXR or ultrasound is unable to resolve relevant management problems. PMID- 7990771 TI - A simple exam to screen superficial masses: fine-needle aspiration cytology. AB - Fine-needle aspiration cytology (FNAC) is now considered a useful tool in the evaluation of adult patients with mass lesions. We reviewed the experience with FNAC in our Paediatric Surgical Department. One hundred and eleven FNACs were performed in children with a superficial mass and no definite diagnosis. All the exams were done by the same physician using a fine needle and no anesthesia. We routinely used May-Gruwald-Giemsa and Papanicolaou staining. Patients age ranged from 20 days to 17 years, with a mean age of 6.5 years. A clinically benign pathology was cytologically confirmed in 90 cases (81%). All children did well at follow-up. Malignancy was diagnosed in eight cases (7.2%) and in all was confirmed with a surgical biopsy. In nine children (8.1%) the specimen was considered insufficient for definite diagnosis. In four cases (3.6%) the pathologist diagnosed a possible malignancy that was excluded at surgical biopsy. The sensitivity was 100% and the specificity was 96%. Our experience confirms that FNAC is a fast, cheap, simple, and accurate diagnostic method and should be used for screening in all children with doubtful superficial masses. PMID- 7990772 TI - Duluth takes on domestic violence. PMID- 7990773 TI - Child abuse. PMID- 7990774 TI - Chemical abuse and family violence in Minnesota. PMID- 7990775 TI - Lines of defense: domestic violence awareness month. PMID- 7990776 TI - Health system reform hangs by a thread. PMID- 7990777 TI - HCMS and AMA work to end abuse in the workplace. PMID- 7990778 TI - Program for impaired health care workers is available. PMID- 7990779 TI - Community integrated service networks. PMID- 7990781 TI - Medicine's identity crisis revealed. The Asclepius vs. the Caduceus. PMID- 7990780 TI - Minnesota health care provider cooperatives. PMID- 7990782 TI - Pervasive violence calls for introspection, intervention. PMID- 7990783 TI - On the front lines. PMID- 7990784 TI - Headache. AB - Headache is very common among women of childbearing age and can be influenced by hormonal fluctuations. When pregnant women develop headache, the cause is usually tension-type headache or migraine, but headache may be a symptom of a more serious neurologic or medical condition. This article discusses the differential diagnosis and management of major causes of headache during pregnancy. PMID- 7990785 TI - Peripheral nerve and neuromuscular disorders. AB - Mononeuropathies, plexopathies, and radiculopathies may occur with increased incidence during pregnancy and the puerperium. Immunologically mediated disorders of peripheral nerve, neuromuscular junction, and muscle have distinctive management problems when they occur during pregnancy. PMID- 7990786 TI - Women with epilepsy. Reproduction and effects of pregnancy on epilepsy. AB - Conventional wisdom and prevailing medical practice strongly support the belief that medication should be avoided during pregnancy. For the nearly one million women of childbearing age with epilepsy in the United States this is often difficult, if not impossible, and for many of these women becoming pregnant raises many conflicting issues. Women with epilepsy may face a possible increase in the frequency and severity of seizures, and in generalized tonic-clonic seizures there is a small but increased risk of miscarriage. PMID- 7990787 TI - Pregnancy and movement disorders. AB - The concurrence of pregnancy and movement disorders is an uncommon event in a general neurologic practice. Even at specialized movement disorder referral centers, there is insufficient experience to adequately guide management of pregnancy, except perhaps in the case of WD. The questions posed most urgently by patients regard the safety of medication, an issue on which there is insufficient data, and their ability to care for a child for at least the next decade, an issue that differs by disease and social situation. The author's formulation of efficacy and toxicity suggests that certain medications commonly used in movement disorders should be discontinued before pregnancy, if possible. These medications include neuroleptics, amantadine, diazepam, primidone, selegiline, and reserpine. Pregnancy may unmask a pre-existing potential for chorea (i.e., chorea gravidarum) and frequently has a mild exacerbating effect on symptoms of PD; however, it has little effect on other movement disorders. Severe generalized dystonia would probably interfere with vaginal delivery, but the scant existing data suggest minimal effect of movement disorders on pregnancy, childbirth, and neonatal health. PMID- 7990788 TI - Demyelinating and neoplastic diseases in pregnancy. AB - Multiple sclerosis (MS) has no significant effect on fertility, conception, fetal viability, and delivery. Exacerbations of MS decrease during pregnancy and increase significantly during the 3 months postpartum. Pregnancy does not increase the risk of brain tumors, but physiologic changes induced by pregnancy affect the diagnosis and biologic behavior of glial tumors, meningiomas and vascular tumors, and pituitary adenomas. MR imaging and computed tomography scanning are the most useful modalities for diagnosis. PMID- 7990789 TI - Neurologic disorders of pregnancy. Connective tissue disorders. AB - Although neurological manifestations are well described in patients with connective tissue diseases, there is no evidence of increased frequency during pregnancy. Treatment varies with the neurological disorder and the nature of pathogenetic process, with modifications of usual therapies sometimes required during pregnancy. Termination of pregnancy is a consideration only with the more serious vasculitic diseases (i.e., PAN or WG), in patients with cardiac or renal failure, or in patients with severe exacerbations of their systemic disease that is refractory to therapy. PMID- 7990790 TI - Neurologic infections of the fetus and newborn. AB - This article concentrates primarily on infections of viral origin, although numerous microorganisms can infect the fetal and newborn brain (see Tables 1 and 2). Intrauterine infections occur most often for HIV, CMV and rubella, whereas HSV is preferentially transmitted intrapartum. In the last decade, changes in the epidemiology of some of the neonatal infections have occurred largely because of the AIDS epidemic. Indeed, pediatric HIV is now the second most frequent viral infection of the newborn (see Table 1) and congenital syphilis has reemerged. Surprisingly, the AIDS epidemic appears to have had minimum impact on infections with other organisms such as Toxoplasma and CMV that commonly infect the brain of adults with AIDS. The recent availability of improved viral diagnostic methods and anti-viral drugs has aided in the identification and treatment of infected newborns. PMID- 7990791 TI - Eclampsia. AB - This article defines and then delineates pre-eclampsia and eclampsia, reviewing the clinical features, neurologic manifestations, and underlying causes. There is a review of the pathophysiology including hypertension, coagulopathy, and cerebral pathology including newer findings involving immune system abnormalities. The diagnosis including laboratory studies, imaging, and electroencephalography. PMID- 7990792 TI - Arterial and venous stroke associated with pregnancy. AB - Pregnancy increases the risk of both arterial and venous strokes. The diverse causes of these strokes warrants a thorough investigation including angiography if needed to secure a diagnosis in order to give the patient the best advice and treatment. The section on arterial stroke reviews the differential diagnosis and highlights how pregnancy influences some conditions causing stroke. The section on cerebral venous thrombosis reviews the clinical scenarios of this unusual condition, the evolving techniques for its diagnosis, and its treatment with anticoagulants. PMID- 7990793 TI - Neuro-intensive care of the pregnant woman. AB - Pregnancy may exacerbate underlying neurologic illness or may precipitate an acute neurologic emergency such as pituitary apoplexy. Care is directed to both mother and fetus in a manner designed to optimize the physiologic stability of both. A "team approach" is often needed. PMID- 7990794 TI - Course of psychiatric disorders in pregnancy. Dilemmas in pharmacologic management. AB - Although it is generally believed that pregnancy is a time of emotional well being, many women develop or have a recurrence of psychiatric illness during this time. The risks associated with leaving a woman untreated during pregnancy are potentially substantial and must be weighed against the risks of exposing the fetus to the potentially teratogenic medications. Large prospective and retrospective studies suggest a relative safety of use of tricyclic antidepressants during pregnancy. Data available for neuroleptics, lithium, benzodiazepines, and the anticonvulsants valproic acid and carbamazepine, although mixed, point to increased risks of congenital malformations in the children of mothers exposed to these agents in the first trimester of pregnancy. Very little is known about the behavioral abnormalities in offspring of mothers exposed to these agents. Animal studies suggest changes in brain receptor number and function in the offspring of mothers on a variety of psychotropic drugs studied to date. The few human studies do not suggest long term effects, but given the very limited data, no definitive conclusions can be drawn. Large epidemiologic follow-up studies of children exposed to medication in utero may help clarify questions relating to behavioral changes and thus help guide clinical decisions. PMID- 7990796 TI - Cigarette smoking among adults--United States, 1993. AB - The annual prevalence of cigarette smoking among adults in the United States declined 40% during 1965-1990 (from 42.4% to 25.5%) (1) but was virtually unchanged during 1990-1992 (2). To determine the prevalence of smoking among adults, smoker interest in quitting, and the prevalence of cessation (i.e., quit ratio) among adults during 1993, the Year 2000 Health Objectives Supplement of the 1993 National Health Interview Survey (NHIS-2000) collected self-reported information about cigarette smoking from a random sample of civilian, noninstitutionalized adults aged > or = 18 years. This report presents the prevalence estimates for 1993 and compares them with estimates from the 1992 Cancer Epidemiology Supplement and presents 1993 estimates for smoker interest in quitting completely and the prevalence of cessation among ever smokers. PMID- 7990795 TI - Legal issues in neurology and pregnancy. The physician's duty of care. AB - Physicians face some unique legal issues when they treat women who have neurologic conditions in their childbearing years. These issues stem from the physician's responsibility to foresee and inform the woman of the impact of her neurologic condition and its treatment on her reproductive choices, as well as on her fetus. The physician's legal responsibility may extend to third parties, including not only the woman's spouse and child, but also to the general public. Legal liability may be imposed on a doctor because of harm to a fetus or to others as a result of the doctor's act or omission involving his patient. PMID- 7990797 TI - Abortion surveillance: preliminary data--United States, 1992. AB - For 1992, CDC received data about legal induced abortions from 52 reporting areas (the 50 states, New York City, and the District of Columbia). This report presents preliminary data for 1992. PMID- 7990798 TI - State-specific trends among women who did not receive prenatal care--United States, 1980-1992. AB - Lack of prenatal care is strongly associated with an increased risk for low birthweight (< 2500 g [< 5 lbs 8 oz] at birth) infants, preterm delivery, and maternal and infant mortality (1). From 1980 through 1992, the nationally aggregated percentage of pregnant women who did not receive prenatal care increased by 31%--from 1.3% to 1.7% (2,3). Because nationally aggregated data can obscure variations among states, CDC analyzed state-specific data derived from birth certificates for 1980-1992 to examine trends among women who did not receive prenatal care. This report summarizes the findings of the analysis. PMID- 7990799 TI - Bolivian hemorrhagic fever--El Beni Department, Bolivia, 1994. AB - In July 1994, an outbreak of Bolivian hemorrhagic fever (BHF), which is caused by Machupo virus, began in northeastern Bolivia. This report describes the investigation and features of this outbreak, the search for additional cases of BHF in El Beni, Bolivia, and results of rodent investigations. PMID- 7990800 TI - [Functional expression of plasma membrane proteins in the Xenopus laevis oocyte system]. AB - A review is presented of the possibilities of using Xenopus oocytes for molecular biological studies. Combination of biochemical, electrophysiological, and molecular-genetic methods applied to a single oocyte provides exceptional conditions for getting information about the biogenesis, structure function relationships, and modulation of plasma membrane proteins. These investigations are provided for by the oocyte ability to efficiently transcribe and translate foreign genetic information, to correctly process nascent polypeptides to target them to the proper subcellular compartment, and to couple them to the oocyte signaling pathways. PMID- 7990801 TI - [Interaction of catalytically active antibodies with oligoribonucleotides]. AB - The interaction of antibodies from blood sera of patients with autoimmune pathology, systemic lupus erythematosus with oligoribonucleotides was studied. The RNA-hydrolyzing activity was shown to be an intrinsic property of autoantibodies. Enzymic activity of antibodies in hydrolysis of poly(U) was estimated at 20-40% of that of RNase A. In contrast to known eukaryotic RNases, the autoantibodies possess a specific RNA-hydrolyzing activity for oligo r(A). The RNA-nicking activity of antibodies in hydrolysis of oligoadenylates was more higher than with hydrolysis of oligo d(A). Optimal conditions of r(pA)13 hydrolysis were selected, including the optimal of pH = 8.7. PMID- 7990803 TI - [Two types of DNA-pairing enzymatic activities detected in rat spermatocyte nuclei: partial purification and characteristics]. AB - Two types of different activity that can promote homologous pairing and strand transfer between suitable DNA substrates have been partially purified from nuclear extracts of rat testes and characterized. Two activities are separated by chromatography on a ssDNA-cellulose column. One activity promotes strand transfer between single-strand circular phage and duplex fragment DNA (346 or 943 bp). The reaction does not require ATP and Mg2+. The other catalyzes only homologous pairing between duplex circular phage and single-strand fragment DNA (346 b). The activity does not need ATP, but requires Mg2+. PMID- 7990802 TI - [The effect of the 5'-leader of potato X-virus on expression of the gene for the potato Y virus membrane protein in transgenic Solanum tuberosum]. AB - The 5'-leader of potato virus X (PVX) genomic RNA was successfully used to generate potato plants expressing the coat protein of the potato virus YN (Russian isolate) (PVY CP). Two expression cassettes were constructed that carried the PVY CP coding sequence along with the PVY 3'untranslated region under the control of the CaMV 35S promoter and poly(A) signal. The cassettes contained different sequences between the 35S promoter and the CP artificial AUG initiating codon of the coat protein: either a polylinker or a shortened variant of the PVX leader. Transgenic Belorusskii-3 potato plants generated by agrobacterial transformation were shown to express the PVY CP gene to different extents depending on the cassette integrated into the plant genome. The cassette containing the PVX leader provided detectable amounts of the coat protein in all tested plants, whereas plants carrying the cassette with the polylinker leader produced no coat protein above the Western detection threshold. Northern analysis revealed that the presence of the PVX leader in front of the PVY CP gene initiating codon resulted in a 10-fold increase in the PVY CP mRNA steady-state levels, thus suggesting an influence of the PVX leader on mRNA stability. PMID- 7990805 TI - [Cloning in the lambda ZAPII/pBluescript system. I. Design of common cDNA libraries]. AB - Here in I summarize some cloning tips that have been revealed during construction of cDNA libraries from rat tissues and mouse stem cell lines in lambda ZAPII, and that improve the cloning efficiency. These improvements can be applied to many different vectors and cDNA cloning systems. PMID- 7990804 TI - [Determination of DNA-binding proteins by countercurrent isotachopheresis on nitrocellulose membranes. I. Antibodies to DNA and its adducts]. AB - A very strong electroosmotic counterflow was produced on nitrocellulose membranes during isotachophoresis in a system of 0.06 M Tris-HCl (pH 6.7) as the leading electrolyte and 0.012 M Tris-beta-alanine (pII 8.6) as the terminating one. This counterflow was equal in rate and opposite in direction to the migration of the Cl-/beta-alanine boundary. The rate of counterflow was much higher than the rate of migration of any organic anions, including different proteins. Double-stranded and single-stranded DNA or its adducts were fixed on the nitrocellulose membrane, and the membrane was blocked with unrelated proteins. DNA-binding proteins, namely antibodies to DNA, followed by peroxidase-conjugated anti-IgG, were introduced into the counterflow, which transferred them one after another to the DNA spots. Thus, sequential binding and washing was performed automatically. In this way, antibodies were detected to ds- and ss-DNA, to BrdU-DNA, to Z-DNA, to biotinylated DNA and DNA modified with trans-Pt, as well as development of biotinylated DNA dots by steptavidin-peroxidase. PMID- 7990806 TI - [Isolation and characteristics of DNA fragments for the region of the tissue plasminogen activator genes and areas adjacent to it in the human genome]. AB - Fragments overlapping the tPA gene and its 5'- and 3'-flanking regions were isolated from human liver DNA library cloned in lambda Charon4A vector. A BglII fragment comprising the 3' end and the adjacent genomic region (total length 3.7 kb) was subcloned in plasmid pUC19 and its restriction map was determined. The nucleotide sequence of the 5' region of this fragment was compared with the 3' end region of the tPA gene and the corresponding regions of five published variants of tPA mRNA cDNA from different tissues; discrepancies in seven positions were revealed, which might be caused by intragenomic polymorphism. PMID- 7990807 TI - [A new method of nonradioactive labelling of oligonucleotides and their use as allele-specific probes for detecting mutations causing beta-thalassemia]. AB - We have developed simple and efficient methods for synthesis of biotin and horseradish peroxidase (HRP)-labeled oligonucleotides. Biotinylated oligonucleotides were obtained in quantitative yields, and oligonucleotide conjugates with HRP in 60-80% yields. Allele-specific oligonucleotide probes for the diagnostics of IVS 1-110 mutation in the beta-globin gene causing beta thalassemia were thus obtained. Temperature conditions for the non-radioactive ASO hybridization with the amplified segment of the human beta-globin gene and wash conditions were selected. HRP-labelled probes were used in hybridization without preliminary separation after synthesis. To decrease nonspecific enzyme binding we have elaborated special conditions for membrane blocking. Detection of the biotinylated probe was carried out with the help of a streptavidin--HRP conjugate. O-Dianisidine was used as a chromogenic substrate. We have demonstrated the usefulness of this method in the analysis of amplified samples of DNA obtained from blood of patients homozygous in the mutant gene, and heterozygous carriers. PMID- 7990808 TI - [Irradiation of DNA with ultraviolet light: potential changes and mutations]. AB - It is proposed a mechanism of formation of potential changes at UV irradiation of DNA. It consists in the changes of tautomers of nucleotide bases provoked by a simultaneously hydrogen atoms transitions of first and second H-bonds in G-C pair. The reason of such transitions are strong atomic vibrations induced by electronic excitation energy into heat transition and also protons excitation. The probability of different lengthening of h-b-1 bond length from equilibrium one are estimated for two different "temperature" of a small fragment. The possibility of formation of a protonic exciton on DNA Fragments consisting only from G-C pairs is demonstrated. The dispersion law of protonic excitation and its group velocity are obtained. The role of such quasiparticles at potential mutations formation is discussed as soon as the origin of "neighbour effects", i.e. way does depend the mutation ability degree of a given nucleotide nature of neighbouring ones. PMID- 7990809 TI - [Expression of the third open reading frame of the drosophila MDG4 retrotransposon similar to the retroviral env-genes, occurring through splicing]. AB - The presence of a third long open reading frame (ORF3) is the common feature of a number of Drosophila retrotransposons, including MDG4 (gypsy). Thus, these elements have a strong structural resemblance to the integrated forms of vertebrate retroviruses. To elucidate the mode of expression of ORF3, transcription analysis of MDG4 for several D. melanogaster strains and Schneider 2 cultured cells was carried out. In all cases the analysis revealed the presence of 2-kb subgenomic ORF3 transcripts in the polyadenylated RNA fractions. It was shown by using the cDNA-PCR technique with different sets of primers that these subgenomic 2-kb RNAs are generated through splicing of full-length MDG4 transcripts. In all cases, only one DNA fragment is amplified for each suitable pair of primers, indicating that there is probable no alternative splicing during the ORF3 expression. The primary structure of spliced RNA was determined, and its analysis shows that both MDG4 subfamilies (6K and 7K) are apparently able to encode functionally active translation products of ORF3. The regulation at the level of splicing is supposed to be one of the most important factors controlling the transposition frequency of MDG4. PMID- 7990810 TI - [DNA fragment DARC146 from a complex form of DNA polymerase alpha contains several nuclear protein binding segments]. AB - Earlier, a number of DNA fragments were identified in the complex form of DNA polymerase alpha. One of them, DARC146, can support autonomous replication in mammalian cells. We have subcloned 146 bp from DARC146 (here called DARC146). This fragment has an ability to replicate autonomously in mammalian cells. This ability permits one to speak about DARC146 as a putative replication origin. From this conclusion, we suggest that all signals for initiation of DNA synthesis are located on the nucleotide sequence under study. Here, we have shown that the nuclear extract contains four polypeptides binding specifically to synthetic oligonucleotides covering the AT-rich region of the DARC146 sequence. The first protein is Oct-1, a nuclear transcription-replication factor. The second protein (named p65) binds to the TCTCTTA site of the DARC146 nucleotide sequence. There are two sites for Oct-1 protein and two sites for p65 in the DARC146 fragment. Octamer motifs and sites for p65 are located tandemly side by side. Moreover, we identified 28kDa polypeptide from nuclear matrix which bound to DARC146. Based upon the data presented, we suggest a hypothetical model of the pre-initiation state of the DARC146 sequence. PMID- 7990811 TI - [Effectiveness of sequencing using stacking hybridization on oligonucleotide matrices with varying length of immobilized oligonucleotides]. AB - The opportunity of enhancing the sequencing efficiency by applying continuous stacking hybridization is considered. The approach is based on the increase of duplex length by continuous stacking hybridization of oligonucleotides added to solution (l-oligonucleotides) to oligonucleotides immobilized on matrix (L oligonucleotides). An analysis of reconstruction efficiency for sequenced fragments up to length of 30000 nucleotides was made. Various combinations of L- and l-oligonucleotide length were considered. The results obtained enable one to evaluate the potentialities of the proposed method for various nucleotide matrices and the complexity of experiment. Use of continuous stacking hybridization permits a considerable increase of the length of sequenced DNA fragments. We offer the approach for resolving ambiguities in branching points, which occur because of long repeats. It is based on continuous stacking hybridization of several l-oligonucleotides which form a "chain" stabilized by mutual stacking interaction. PMID- 7990812 TI - [Low affinity human IgE receptor: cloning cDNA from B-lymphocytes of cell line 1B and study of its expression in peripheral blood B-cells]. AB - Previously, the cDNA coding for human low-affinity receptor for IgE (FcERII/CD23) was cloned by three independent groups. Using oligonucleotide probes corresponding to the published cDNA sequence of CD23, we have isolated cDNA clones encoding FcERII from the cDNA library of B-lymphoblastoid cell line 1B obtained in our laboratory. Cloned nucleotide sequences of FcERII were shown to be identical to those from the RPMI8866 cell line. Using a DNA fragment containing the full-length cDNA copy of CD23 as a probe, CD23 expression in highly purified peripheral blood B lymphocytes was shown to be induced by recombinant human IL4 in a clearly dose-dependent manner. PMID- 7990814 TI - [A rapid and precise method for lattice approximation of the course of a protein chain based on a dynamic programming algorithm]. AB - Application of a dynamic programming method allows one to find the best possible lattice model of a protein chain fold for any lattice and any orientation of the protein relative to the lattice. Special repulsive potentials help to obtain the self-avoiding lattice models of protein folds. The quality of approximation increases when the distance between neighbor chain links is not fixed rigidly. The calculations carried out for the proteins of different structural classes show a high efficiency and precision of this method in comparison with other ones. PMID- 7990813 TI - [Design of the human GM-CSF gene using the polymerase chain reaction and its expression in Pseudomonas putida cells]. AB - Construction of human GM-CSF gene was conducted by the PCR technique. Four exons of GM-CSF gene were synthesized on the basis of human blood DNA using thermostable Tth DNA polymerase. Synthetic oligonucleotides were used as primers. The oligonucleotides contained sequences complementary to the ends of exons. Joining of exons was conducted by reciprocal complementation of the terminal sequences, followed by filling and amplification of the joined products. In most cases the effective synthesis of exons and joined products was possible only after optimizing the polymerase reaction conditions for each primer pair. Determination of the nucleotide sequence of the synthetic gene showed complete identity with the natural one. The gene was introduced into an expression vector under control of the promoter tandem (tac+lac). Expression of the GM-CSF gene was obtained in Pseudomonas putida cells. The recombinant protein had biological activity. PMID- 7990815 TI - [Segments initiating replication of the dihydrofolate reductase domain and the DNA fragment DARC146 interact with the same nuclear proteins]. AB - Comparison analysis was made of the putative replication origin DARC146 and the origin determined in the DNFR domain of CHO cells. We failed to observe extensive homology between these two sequences. However, several short (8-10 bp) areas of homology were identified. Some of them are binding sites for nuclear proteins. As shown by GM and competition experiments, both origins contain high-affinity binding sites for the transcription-replication factor Oct-1 and for two unknown nuclear factors. The two unknown nuclear factors bound to TCTCTTA and CACTTAG nucleotides. The binding sites for these proteins are located at a short distance from each other. This fact suggests interaction between these polypeptides. Measurement of DNA-binding activity of Oct-1 during the cell cycle of proliferating hepatocyte demonstrated that the binding activity of Oct-1 protein increased before initiation of DNA synthesis. The results of this report suggest that Oct-1 and two other nuclear proteins participate in the regulation of mammalian DNA replication. The results published early indicated the presence of an unusual DNA structure (bent DNA) in both origins under study. We suggest that these common elements of the origins regulate their activation. PMID- 7990816 TI - [Inhibitory analysis of DNA polymerase of herpes simplex type 1]. AB - The inhibitory potency of new analogs of nucleoside 5'-triphosphates modified at the sugar residue and or alpha-phosphate against herpes simplex virus type 1 DNA polymerase has been evaluated in a cell-free system containing M13mp10 phage DNA and a synthetic primer. Triphosphates of new acyclic nucleosides [1-(5-hydroxy-2 cis-pentenyl)nucleosides] were the most effective inhibitors among 15 types of nucleoside 5'-triphosphates under investigation, being threefold less active than acyclovirtriphosphate. 5'-Phosphonylmethyl-2'-deoxythymidine beta, gamma diphosphate proved to be a poor substrate for DNA polymerase. Compounds with other modifications at alpha-phosphate were inactive. Constants of hydrolysis rate of acyclonucleosides incorporated into the 3' end of primer were determined. PMID- 7990817 TI - [Quantitative processing of results of uniparametric fluorescent flow analysis of human chromosomes]. AB - The proposed procedure of computer analysis of the flow karyotype data, obtained in human chromosomes studies, is able to provide information about the basic parameters of the karyotypes: the positions of the peaks (corresponding to the relative size of chromosomes), peaks areas (relative number of chromosomes in the sample), coefficients of variation (CV) of the peaks--possible differences between homologous chromosomes. The analysis is based on the assumption that all chromosomal components of the experimental distributions are normal (Gaussians). The algorithm of the analysis uses a combination of two approaches: truncation method and least squares method. As the flow data are "contaminated" by background components, special tools for filtering off the contaminating signals were designed including the original integral Fourier filtering procedure. This analysis is realized in a program package utilizing IBM-compatible PCs. The user is able to get the desired parameters for most chromosomes of the karyotype under study from univariate flow data: differences between particular homologous chromosomes, presence of chromosome aberrations, extra chromosomes, etc., since structural aberrations and chromosome number variation lead to specific changes of the parameters of chromosome-related components. PMID- 7990818 TI - [Analysis of the sequence of the endogenous Djungarian hamster provirus (MRS-Ps) related to the murine mammary cancer virus]. AB - The complete nucleotide sequence of the dwarf hamster endogenous retrovirus (MRS Ps) related to the mouse mammary tumor virus is presented. MRS-Ps has a typical retroviral structure, it is 6980 bp long with LTRs of ca. 880 base pairs at both ends. LTRs carry the usual signals for transcription control. MRS-Ps genes had formerly coded for viral proteins (protease, revertase, and envelope proteins) but have been spoiled by numerous point mutations. Evolutionary relationships with other retroviruses are discussed on the basis of computer analysis of the MRS-Ps sequence. PMID- 7990820 TI - [Structural elements of 80S ribosomes located near the 5'-region of the mRNA binding center]. AB - Affinity labeling of 80S ribosomes with 4-(N-2-chloroethyl-N methylamino)benzylmethylphosphoramides of oligoribonucleotides [32P]AUGUn--mRNA analogs--was studied in three model complexes: 80S.ClRCH2N(CH3)-pAUGU6.Met(Phe)2 trRNA(Phe), 80S.ClRCH2N(CH3)pAUGU3.MetPhe-tRNA(Phe), and 80S.ClRCH2N(CH3) pAUG.Met- tRNA(Met). Two of these complexes imitate the posttranslocational state of 80S ribosomes. Small subunits were labeled preferentially; both 18S rRNA and ribosomal proteins were modified by the mRNA analogs. The relative modification extents of proteins and rRNA depended on the length of the reagent oligoribonucleotide moiety. Extension of the latter resulted in decrease in the relative extent of 18S rRNA modification from 95 a to 16% (for proteins, increase from 5 to 84%, respectively). Fragments of 18S rRNA containing cross-linking sites were identified using blot hybridization. In all cases, fragment 976-1164 was found to be modified. In the case of ClRCH2N(CH3)pAUGU6, labeling occurred also within fragments 593-673 and 1748-1869. Analysis of the modified proteins revealed that proteins S14/S15 were labeled with all three reagents and were the single target of modification with ClRCH2N(CH3)pAUGU6. Proteins S3/S3a, S6, and S16/S18 were modified only with ClRCH2N(CH3)pAUGU3; protein S20 only with ClRCH2N(CH3)pAUG; and proteins S5 and S17 were labeled with both reagents (n = 0, 3). PMID- 7990819 TI - [Transcription of antisense RNA for the human c-myc gene]. AB - Antisense RNA transcription of human c-myc gene has been examined in HeLa, Burkitt lymphoma BL-60 t(8;22) cells, and diploid fibroblasts. By means of the primer extension technique two startpoints of antisense transcription have been detected and mapped with the first (untranslated) exon of the c-myc gene. Similarity between the antisense nucleotide sequence of the first c-myc intron and the SV40 DNA fragment containing the binding sites for transcriptions factors GT-I, GT-II, TC-I, and TC-II has been revealed by computer analysis. It has been established that the DNA fragment of the first c-myc intron is able to form complexes with proteins from the HeLa cell extract. Three nucleotide sequences (TTTCTG, TTTTTA, and TGACTTGTC) are involved in the reactions. These data imply that the c-myc antisense transcripts might take part in the regulation of human c myc gene expression. PMID- 7990821 TI - [Study of the poly(U)-dependent interaction of tRNA(Phe) with the P-site of Escherichia coli ribosomes by chemical modification with nitrosoethylurea]. AB - The accessibility of phosphates in E. coli tRNA(Phe) bound to E. coli ribosomes and 30S subunits for attack by an alkylating agent ethylnitrosourea was studied. The experimental technique allowed us to investigate a part of the molecule between N-11 and N-72. Being bound to the poly(U)-programmed P site of 30S subunit, tRNA(Phe) reveals protection in a discrete region including phosphates 23-44. This region corresponds to the hairpin formed from the anticodon arm and the adjoining 3' strand of the D stem and the variable loop. On the P site of 70S poly(U), additional protection was observed in a region between N-45 and N-63. This region corresponds to the extra loop and T stem, and reveals a fine structure of protection: protected phosphates in positions 45-49, 51, 54-55, 58 61, and 63 alternate with unprotected ones in positions 50, 52-53, 56-57 and 62. We conclude that ethylnitrosourea can be used for detailed study of tRNA-ribosome contacts. PMID- 7990822 TI - [Study of the effect of halogen series anions on DNA molecular conformation in solution]. AB - Effect of halogen-series anions (F-, Cl-, Br-, I-) in sodium, potassium and ammonium halogide solutions with ionic strengths of mu = 0.1, 0.01, and 0.005 M on the dimensions and thermodynamic rigidity of the DNA molecule in solution was studied by viscosimetry and flow birefrigence. Flow birefrigence measurements showed that close-range interactions along the macromolecular chain and accordingly the persistent length of DNA did not change with a change of anion. However, the specific volume of the molecule depends on the anion type. In our opinion, the observed effect is connected with the different ability of anions to "neutralize" the cation screening effect on DNA phosphates. PMID- 7990823 TI - [Secondary structure of the M2 protein of influenza type A virus and its role in forming resistance to rimantadine and deitiforin]. AB - Studies of the molecular aspects of resistance of influenza virus A to drugs (rimantadine, deytiforine, amantadine) allow a purposeful design of new compounds with a broad spectrum of antiviral activity and evoking no resistance. In this work the nucleotide sequence of rimantadine- and deytiforine-resistant influenza A strain Leningrad/156/83 (H3N2) was compared with that of A/Victoria/35/72. The influence of aminoacid substitutions in the M2 protein on its secondary structure in the membrane and its role in resistance development was shown. PMID- 7990824 TI - [Analysis of defects in the structure of the complex poly(G).poly(C)]. AB - The concentration of free poly(C) in solution in the course of its interaction with poly(G) as well as in the presence of preformed complex poly(G).poly(C) was measured by differential pulse polarography (DPP) at a mercury dropping electrode. Poly(C) binding with poly(G) was shown to hamper its electrochemical interaction with the mercury electrode and registration by DPP. It was concluded that the extremely low DPP signal from poly(C) in the presence of preformed complex was the result of its interaction with the distortions in the secondary structure of complex molecules containing free guanines. For quantitative testing of these defects, measurement of Tb3+ ion fluorescence was applied. It was shown that preliminary denaturation of the poly(G) secondary structure reduced the amount of structural defects in the complex and restored of complete DPP registration of redundant poly(C) added to this complex. These results show that the combination of DPP and Tb3+ fluorescence measurements permits one to detect at the quantitative level the structural defects in the poly(G).poly(C) complex. PMID- 7990825 TI - [The concept of the "accessible surface" of the protein within the framework of tritium planigraphy. Experiment and calculation]. AB - Tritium planigraphy allows one to determine the sterical accessibility of protein hydrocarbon fragments (CH, CH2, CH3 groups) for interaction with tritium atoms on condition of direct transit of the bombarding particles. Using lysozyme as a test system, it was shown to be possible to use these data for the description of protein accessible surface area in terms defined by Lee and Richards. The best agreement between experimental and theoretical results was achieved for an effective radius of the testing probe of 0.9 A. Coefficients were obtained that allowed calculation of the accessibility of amino acid residue as a whole using data about its hydrocarbon fragment accessibility. PMID- 7990826 TI - [Use of frequency analysis for localization of functionally important regions of thermolysin]. AB - A theoretical investigation of the functional topography of thermolysin molecule was carried out using frequency analysis of its primary and tertiary structures. The statistical validity of predictions was estimated for the enzyme active site, substrate-binding pocket, interdomain interface, and calcium-binding sites. It was shown that frequency analysis of primary structure could be employed to predict the localization of contiguous parts of the interdomain interface. Primary structure analysis cannot be used to search for the conformation dependent enzyme active site and substrate-binding pocket. On the contrary, frequency analysis of interresidues contacts is not so effective for prediction of the interdomain interface as compared with active site, substrate-binding pocket, and calcium-binding sites. The set of original algorithms proposed could be used in searching for functional sites in various proteins. PMID- 7990827 TI - [Cloning and sequencing the cDNA for the beta-subunit of Baikal omul gonadotropin]. AB - Two types of cDNA encoding gonadotropin beta subunits (GTH beta) were isolated from a cDNA library prepared from pituitary gland of Baikal omul (Coregonus autumnalis migratorius Georgi). The nucleotide sequences of cDNA were determined. The CTHI beta and GTHII beta cDNAs code for polypeptides of 137 and 142 amino acids, respectively. Both of them include a putative signal peptide of 24 amino acids. The predicted amino acid structures of omul gonadotropins were compared with those of other vertebrate species. PMID- 7990828 TI - [Primary structure of DNA, complementary for mRNA for the Baikal omul growth hormone]. AB - The pregrowth hormone DNA was synthesized by polymerase chain reaction from a pituitary gland cDNA library of Baikal omul (Coregonus autumnalis Pallas). A cDNA was sequenced and found to encode a precursor protein of 210 amino acid residues, which included a putative signal peptide of 22 amino acid residues. Sequence comparison reveals close similarity of the omul growth hormone to those of other Salmoniformes species. PMID- 7990829 TI - [Use of the hygromycin phosphotransferase gene as the dominant selective marker for Chlamydomonas reinhardtii transformation]. AB - The hygromycin phosphotransferase gene (hpt) from E. coli under the control of the SV40 early promoter was used as a dominant selectable marker for transformation of Chlamydomonas reinhardtii. Cells were transformed by electroporation (pulse length, 2 ms, field strength, 1 kV/cm). The culture growth phase was a crucial parameter for transformation (optimal density approximately 10(6) cells/ml). It was possible to obtain approximately 10(3) Hyg-resistant colonies under these conditions. Foreign DNA integrated into the Chlamydomonas genome was maintained for at least 8 months but the Hyg-resistant phenotype of the transformed clones was unstable. The frequency of codon usage in the hpt gene was compared with the one in Chlamydomonas nuclear genes. It is supposed that highly biased codon usage in Chlamydomonas does not preclude expression. Advantages of this selection system for studying Chlamydomonas transformation by heterologous genes are discussed. PMID- 7990830 TI - [Kinetics of cyclization, coupled with ligated oligonucleotide modules, as a means of studying DNA bends]. AB - A theoretical study of cyclization accompanying multimerization of oligonucleotide blocks is presented. The primary binding due to the cohesive ends of the blocks is subject to subsequent enzyme-catalyzed covalent fixation. Conditions were found for determining the thermodynamic probabilities of circular DNA conformations from the experimentally measurable rates of cyclization. An exact analytical description for the dynamics of multimerization without cyclization and an approximate description for cyclization accompanying multimerization are given. PMID- 7990831 TI - [Expression of the Epstein-Barr virus terminal repeat protein 1 in Escherichia coli cells]. AB - A pMAL-vector-based plasmid clone with synthetic tac-promotor effectively expressing full-length terminal repeats protein 1 (TP1) of Epstein-Barr virus (EBV) in E. coli was constructed. It is important that the N-terminal region of recombinant TP1 was represented by a maltose-binding protein. The latter can be used to separate TP1 from bacterial lysate by affinity chromatography. Moreover, after treatment with the proteolytic factor Xa, full-length TP1 can be recovered in a discrete form. On the basis of the pATH tryptophan-regulated vector, several plasmid clones expressing different fragments of N- and C-terminal regions of TP1 were also constructed. This collection of recombinant proteins could be used as an important tool for obtaining corresponding antisera and for immunological mapping of the TP1 molecule. PMID- 7990832 TI - [Molecular mechanisms of mutations, arising during formation of 8-hydroxyguanine in DNA]. AB - To reveal the molecular mechanisms of genotoxic effects of oxidation and irradiation, molecular mechanics computations were performed for double-helical olygonucleotides with 8-oxoguanine:adenine (OG.A) pairs in two configurations. Substitution of a T.A pair by OG(syn).A one results in minor changes of intramolecular interaction energy and of the conformational parameters of helixes. Nearly all the interproton distances in low-energy conformations of d(CCACTAOGTCACC):d(GGTGAATAGTGG) with a OG(syn).A pair are within the limits determined from NMR data. These results confirm the suggestion that such pairs can be formed in nucleic acid biosynthesis. The computations have shown that the interaction energies in the minima for duplexes with OG(anti).A and OG(syn).A pairs differ from one another by only 1 to 3 kcal/mol. This difference depends on the nucleotide context. These results allow one to suppose that the configuration of the OG.A pair in the double helix and, as a consequence, the induced mutation probability depends on interactions with its environment (neighboring base pairs and solvent). PMID- 7990834 TI - [Study of the oligonucleotide binding sites on an immunoglobulin molecule]. AB - Interaction of IgG molecules with oligonucleotides using reactive derivatives of p(T)16 bearing a 4-[(N-2-chloroethyl-N-methyl)amino]benzylamine residue at the 5' terminal phosphate was investigated. The modified immunoglobulins were degraded with pepsin into Fab and Fc fragments and by incomplete CNBr hydrolysis into smaller peptides. It became obvious from the analysis of the peptides obtained that the oligonucleotides contacted with immunoglobulins at the antigen-binding Fab fragment of the molecule. The site of interaction is localized in the light chain N-terminal fragment 178 amino acids long. These facts are in accordance with our previous data about the ability of a specific antigen to prevent the oligonucleotide-antibody interaction. On the contrary, an oligonucleotide covalently linked with immunoglobulin could not prevent the antigen-antibody reaction. Monoclonal Fab fragments modified with the alkylating p(T)16 derivative were found to interact with the specific antigen (human myoglobin) during affinity chromatography. This interaction deserves further investigation because of its importance in studying the fate of oligonucleotides in vivo. PMID- 7990833 TI - [Synthesis and secretion of human atrial natriuretic factor in Escherichia coli cells]. AB - A recombinant plasmid providing for the synthesis and secretion of the human atrial natriuretic peptide (hANP) as a C-terminal hybrid with the St. aureus protein A was constructed. The level of secretion of the chimeric proteins and their proteolytic stability were shown to depend upon the genotype of the recipient strains and the cultivation conditions. The hybrid proteins were purified by chromatography on IgG Sepharose. The presence of peptides corresponding to the hANP in the acid hydrolysates of the secreted and affinity purified proteins was confirmed by the enzyme-linked immunoassay and analytical HPLC. PMID- 7990835 TI - [Use of peptides of major histocompatibility type I molecules for induction of specific T-suppressors in vivo in an allogeneic system and extending the life of a murine skin transplant]. AB - Six synthetic peptides represented as variable sequences of the MHC class 1 molecule H-2Kb were synthesized. Appropriate conditions were elaborated for induction of specific suppressor T cells in vivo by peptide 6 (alpha 2 domain) that is introduced intravenously in a dose of 33 micrograms into the tail vein or 100 micrograms into the orbital venous sinus with subsequent testing for inhibition of proliferation in vitro in response to irradiated stimulator cells Kb (BL/6), whereas the stimulator Kk (B10.BR) did not induce any suppressor activity. Of six different peptides tested, suppressor T cells were induced efficiently by peptides 2 (domain alpha 1), 5, and 6 (domain alpha 2), while the highest suppressor efficiency was realized by i/v injection of peptide 2 into mice preimmunized with EL-4 cells. In the same conditions in vivo, immunization by peptides did not induce any cytotoxic T lymphocytes (CTL). In contrast, specific CTL of high efficiency were induced when memory cells were incubated in vitro with heated BL/6 stimulator cells for 4 days. Intravenous injections of peptide 6 into mice gave rise to prolongation of (BL/6 or B10.MBR) skin graft retention Kb when transferred into allogeneic R101 and B10.AKM mice, respectively, but had no influence on rejection of skin grafts from foreign donors of Kk (B10.BR) or Kd (DBA/2) haplotype, respectively. PMID- 7990836 TI - [Interaction of a synthetic peptide, containing a part of the DNA-binding domain of the v-jun transcription activator, with DNA]. AB - Synthesis and DNA-binding activity of the synthetic 26-residue peptide, containing in two copies a part of the DNA-binding domain of the transcription activator v-Jun, are reported. Using CD spectroscopy, it has been shown that the peptide exists in a random coil conformation in aqueous solution, but assumes partially an alpha-helical conformation in the presence of 20% trifluoroethanol. The percentage of alpha-helix is increased in the presence of 40% trifluoroethanol up to approximately 80%. It has been shown that the peptide forms two types of complexes with DNA. The first type of complexes saturates when one peptide molecule occupies six base pairs. At further increase of molar peptide to DNA ratio the binding became a cooperative process. The binding approaches saturation when one peptide molecule is bound approximately to four DNA base pairs. The binding constant of the monomer peptide complex with DNA has been estimated to be approximately 1.10(5) M-1 in the presence of 0.2 M NaCl. The peptide binds more strongly to poly(dG).poly(dC) and poly(dA).poly(dT) than to poly[d(GC)].poly[d(GC)]. We found that the DNA minor groove-binding antibiotic distamycin A competes effectively with the peptide for binding to poly(dA).poly(dT). PMID- 7990837 TI - [Synthesis and interaction of two peptides, modeling the DNA-binding domain of the v-jun transcription activator, with DNA]. AB - Synthesis and DNA-binding activities of the two synthetic 26-residue peptides, containing in two copies a part of the DNA-binding region of the transcription activator v-Jun, are reported. Aminoacid sequences of the two peptides are identical, but in one of them the structure of the DNA-binding region is stabilized by S-S-bond between the two cysteine residues. Using CD spectroscopy, it is shown that the two peptides exist in a random coil conformation in aqueous solution, but assume partially an alpha-helical conformation in the presence of 20% trifluoroethanol. The percentage of alpha-helix is increased in the presence of 40% trifluoroethanol up to approximately 65% and 40% in the absence and presence of S-S-bond between the two cysteine residues, respectively. Evidently, formation of S-S-bond prevents a coil to alpha-helix transition in one of the two DNA-binding regions of the peptide, whereas the formation of alpha-helix in another DNA-binding region is allowed. It is shown that the two peptides bind to DNA. We found that the DNA minor groove-binding antibiotic distamycin A competes with the two peptides for binding to poly(dA).poly(dT). The binding of the two peptides to DNA is accompanied by conformational transitions in the peptide molecules, whereas the structure of DNA does not undergo a marked change. The difference CD spectrum obtained by subtracting the spectrum of DNA from the spectrum of a peptide-DNA mixture differs from the CD spectrum of the free peptide. The shapes of the difference CD spectra are consistent with alpha-beta and coil-beta transitions induced upon binding of the two peptides to DNA. DNase I footprinting diagrams show that peptides mediated cleavage protection of DNA takes place at regions containing 5'-TGA-3' and 5'-TGC-3' nucleotide sequences. PMID- 7990838 TI - [Subregional localization of recombinant cosmids, containing microsatellite sequences, on human chromosome 13]. AB - Twenty four recombinant cosmids were subregionally localized by fluorescent in situ hybridization on human chromosomes. Fifteen of the clones were found to belong to only one chromosome: 13 clones located on chromosome 13, one located on chromosome 1, and one on chromosome 11. Nine cosmids were located in nuclear organizer regions. The clones gave signals from NOR regions of chromosome 13 and all other chromosomes containing the NOR region. The cosmid probes were selected from the chromosome 13 cosmid library as ones containing microsatellite repeats with motifs GACA, GACT, GATG, TCC, and CA. Each of the 9 clones located in the NOR region contains microsatellites GACA and TCC. Among the 15 clones giving unique signals, we found 9 clones with the GACT microsatellite, and three clones containing one of the microsatellites GATG, TCC, and CA. These microsatellite containing clones can be used to make polymorphic genetic markers for fine genetic mapping of chromosome 13. PMID- 7990839 TI - [Expression of a partially modified delta-endotoxin gene from Bacillus thuringiensis var. tenebrionis in transgenic potato plants]. AB - A modified gene (Bt77) of delta-endotoxin from Bacillus thuringiensis var. tenebrionis was constructed and cloned into pMON505. This binary transformation vector was introduced into Agrobacterium tumefaciens strains containing different helper disarmed Ti-plasmids, LBA4404, A281, and CBE21. These Agrobacterium strains were used to transform potato stem segments (S. tuberosum, cv Desiree, Resy, Temp, Granat). Regenerants were selected on kanamycin-containing media. The presence of the Bt77 sequence in plant genomic DNA was confirmed by PCR analysis. Bt gene expression was studied in regenerated plants. Western blot analysis revealed that transgenic plants produced the Bt protein in the range of 0.005 0.02% of total protein. Total protection against insect damage of leaf tissue from these plants was observed in laboratory bioassays with of Colorado beetle larvae. Transgenic plants showed incomplete protection from CB larvae. PMID- 7990840 TI - [A new method of covalent immobilization of oligodeoxyribonucleotides on nylon membranes for hybridization with nucleic acids]. AB - A new method of covalent immobilization of oligodeoxyribonucleotides on nylon membranes which contain surface amino groups was developed. The method consists in condensation between the amino group of the membrane and the carboxyl group of modified oligonucleotide by means of 1-ethyl-3-(3' dimethylaminopropyl)carbodiimide. The carboxyl group was introduced into the oligonucleotide by means of postsynthetic attachment of peptide (reduced glutathione) at the terminal phosphate group of the oligonucleotide, using the N hydroxybenzotriazole method of phosphate activation. Membranes containing a covalently immobilized 23-membered oligonucleotide were tested in hybridization with complementary oligonucleotide, and with single-stranded DNA of bacteriophage M13 which has a complementary sequence. The method of covalent immobilization is very simple and convenient. The membranes with covalently immobilized oligonucleotides may be used not only in hybridization analysis, but also for purification of nucleic acids and proteins which recognize nucleotide sequences and in sense biotechnology. PMID- 7990841 TI - [A model prokaryotic promotor. III. Cloning and study of functional activity in vivo]. AB - The efficiency of two schemes of oligonucleotide-directed insertion mutagenesis was studied in comparison with standard cloning of DNA duplexes based on blunt end ligation. Using new approaches, the 30-bp consensus-like prokaryotic promoter was inserted in proper orientation in a promoter-testing plasmid at an almost 100% frequency. Data on the marker gal operon expression and S1-nuclease mapping of the transcription initiation points indicate formation of an active promoter in the region of the insertion. PMID- 7990842 TI - [Transcription of eukaryotic ribosomal RNA genes]. AB - The literature data about eukaryotic cytoplasmic ribosomal RNA (rRNA) are cited in this review. Ribosomal gene regulatory elements (promoters, enhancers, terminators) and protein factors of RNA polymerase I transcription are considered. A separate chapter is dedicated to Protista rRNA transcription. PMID- 7990843 TI - [Structure of aminoacyl-tRNA-synthetase of higher eukaryotes from molecular cloning data]. AB - This review summarizes the data on the primary structure of eukaryotic aminoacyl tRNA synthetases (EC 6.1.1) obtained during last decade by means of molecular cloning of respective cDNAs. This structural information is compared with that available for bacterial species. The alignment of E. coli, yeast and mammalian sequences are presented. The N- and C-terminal extensions of higher-eukaryotic aminoacyl-tRNA synthetases are discussed in view of their chimeric origin and potential functions. For some enzymes, the exon/intron organization of their genes are compared. A possible relationship between the domain structure of the protein and the exon/intron organization of the gene is considered. PMID- 7990844 TI - [Protein phosphatases: structure and function]. AB - The process of protein and enzyme systems phosphorylation is necessary for cell growth, differentiation and preparation for division and mitosis. The conformation changes of protein as a result of phosphorylation lead to increased enzyme activity and enhanced affinity to substrates. A large group of enzymes- protein kinases--is responsible for phosphorylation process in cell, which are divided into tyrosine- and serine-threonine-kinases depending on their ability to phosphorylate appropriate amino acid residues. In this review has been considered the functional importance and structure of protein phosphatases--enzymes, which are functional antagonists of protein kinases. PMID- 7990845 TI - Movement disorders following lesions of the thalamus or subthalamic region. AB - Reports of 62 cases with a movement disorder associated with a focal lesion in the thalamus and/or subthalamic region were analyzed. Thirty-three cases had a lesion confined to the thalamus. Sixteen cases had a thalamic lesion extending into the subthalamic region and/or midbrain. Thirteen cases had a lesion in the subthalamic region or a subthalamic lesion extending into the midbrain. Nineteen cases with dystonia, 18 with asterixis, 17 with ballism-chorea, three with paroxysmal dystonia, and five with clonic or myorhythmic movements have been described. No case with isolated tremor has been described. In 53 cases with unilateral thalamic or subthalamic lesions, all but one with bilateral blepharospasm (associated with right posterior thalamic, pontomesencephalic, and bilateral cerebellar lesions) had dyskinesias in the limbs contralateral to the lesion. The other nine cases had bilateral paramedian thalamic lesions; seven developed bilateral dyskinesias, and the remaining two had unilateral dyskinesias. Regarding the 19 patients with dystonia, the two with bilateral blepharospasm had thalamic and upper brainstem lesions, and one with hemidystonia and torticollis had a subthalamic lesion. The other 16 patients all had a unilateral thalamic lesion with contralateral dystonia (10 hemidystonia, five focal dystonia affecting a hand and/or and one segmental dystonia involving face, arm, and hand). The exact location of the thalamic lesion was mentioned in 10 cases; the posterior or posterolateral thalamus was involved in six and the paramedian thalamus in four. These areas are more posterior or medial to the ventrolateral and ventroanterior thalamic nuclei, which receive pallido-thalamic and nigro-thalamic afferents. Two cases developed dystonia immediately after thalamotomy, and one case developed it 4 days after head trauma. The others initially had a hemiplegia and developed dystonia 1-9 months after the acute insult. Fifteen of the 17 patients with chorea had a unilateral lesion in the subthalamic nucleus or subthalamic region (eight due to infarcts, one to hemorrhage, five to mass lesions, and one to multiple sclerosis). All had contralateral hemichorea or hemiballism. One other case had bilateral chorea of the hands and tongue due to paramedian thalamic infarction. Another case with generalized chorea and thalamic atrophy was complicated by stereotaxic surgery. Thirteen of the 18 cases with asterixis had lesions confined to the thalamus. Eight were associated with thalamotomy, and five others had a stroke (four infarction and one hemorrhage) affecting the contralateral thalamus.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 7990846 TI - Parkinsonian syndromes associated with hydrocephalus: case reports, a review of the literature, and pathophysiological hypotheses. AB - We present nine cases of obstructive hydrocephalus (OH) associated with marked parkinsonism. Four patients had noncommunicating OH (NCOH) [three nontumoral aqueductal stenosis (AS), one tumoral AS]. The presentation was that of acute or subacute parkinsonism, usually at the time of acute recurrent ventricular obstruction. Three had a marked response to levodopa and required short-term treatment after shunting. However, one has remained levodopa dependent after 2 1/2 years. Three of the five patients with communicating OH (COH) presented with shunt-responsive normal pressure hydrocephalus (NPH), only later to develop progressive parkinsonism. One of these was found to have progressive supranuclear palsy (PSP) at autopsy and PSP was clinically suspected in one other patient. A third had an atypical course suggestive of PSP; however, autopsy demonstrated the combination of Lewy body parkinsonism and the sequelae of hydrocephalus. The remaining two COH patients presented with levodopa-responsive parkinsonism. Subsequent clinical features and imaging studies suggested the presence of NPH. The pathophysiology of hydrocephalic parkinsonism probably involves variable sites of dysfunction in the nigrostriatal pathway and/or the cortico-striato pallido-thalamo-cortical circuit. At certain locations these pathways lie in close proximity to the ventricular system and may be subjected to mass effects and ischemic changes secondary to ventriculomegaly. The additional importance of possible associations between subcortical cerebral ischemia, NPH, and "degenerative" disorders such as PSP and Parkinson's disease is discussed. PMID- 7990847 TI - Characteristics of handwriting of patients with Huntington's disease. AB - Patients with Huntington's disease exhibit poorer-quality handwriting, sometimes clinically exhibiting macrographia, an increase in the size of handwriting. To characterize deficits in handwriting of patients with Huntington's disease, we compared the writing of 12 young, 12 age-matched controls, and 12 patients with Huntington's disease. Subjects were asked to write the letter "l" four times, at a constant length, on a graphics tablet that sampled pen position at 200 Hz. Huntington's disease causes chorea (involuntary movement), akinesia (difficulty in initiating voluntary movement), and bradykinesia (slowness and difficulty in maintaining voluntary movement). To distinguish changes in handwriting quality due to involuntary movement from impairments of voluntary movement, handwriting samples with obvious choreic movements were analyzed separately from other handwriting samples. Several measures of quality of handwriting were considered, based on: the regularity and consistency of handwriting, the efficiency of movement trajectories, and the proportions of movement occurring at specific frequencies. Results suggested that Huntington's disease increases variability of movement parameters, and causes problems in producing smooth movements. Choreic movement was best characterized by the number of zero crossings in the velocity function relative to the prescribed number of writing strokes. We hypothesize that macrographia in Huntington's disease occurs when chorea predominates over bradykinesia. Comparisons were made between the handwriting of patients with Huntington's and Parkinson's diseases. PMID- 7990848 TI - Unusual focal dyskinesias: the ears, the shoulders, the back, and the abdomen. AB - Fourteen patients with focal or segmental involuntary movements affecting the ears, back, shoulder girdle, and upper extremity, as well as the abdomen and pelvic girdle, are presented. The unusual locations and appearance of these dyskinesias distinguishes them from recognized movement disorder syndromes. It is argued that the slow, sinuous, and semirhythmic character of the movements and the variable long-duration bursts of motor unit activity responsible for them most closely fit into the spectrum of dystonia. A history of pain in the affected region and/or peripheral trauma in some cases also suggests that peripheral factors may play a role in their pathogenesis. PMID- 7990849 TI - Akathisia in Parkinson's disease. AB - This study evaluated the prevalence and clinical characteristics of akathisia in a tertiary care Parkinson's disease (PD) practice, and assessed the agreement between investigators for the diagnosis of akathisia in PD, and the sensitivity and specificity of a brief patient questionnaire. Fifty-six consecutive PD patients completed an akathisia questionnaire and then were clinically evaluated for akathisia by two examiners blinded to the patient questionnaire. Overall, 45% of PD patients had akathisia as determined by clinical evaluation. Interrater reliability for the diagnosis of akathisia was high (K = 0.89). Patient self report of restlessness agreed with examiner diagnosis in 89% of the patients. The presence of akathisia was associated with the severity and age of onset of PD. Symptoms most frequently affected the legs, and associated movements were suppressible for brief periods. PMID- 7990850 TI - Neurological sequelae following carbon monoxide poisoning clinical course and outcome according to the clinical types and brain computed tomography scan findings. AB - The prognosis for patients who survive carbon monoxide (CO) poisoning is uncertain, particularly in those who develop persistent neurological complications after recovery from the initial coma. Thirty-one patients with the sequelae of CO poisoning, followed for a year, are described. Eight had a progressive course, and 23 had a delayed relapse after an initial recovery period of approximately 20 days (range, 1-36 days). Those with a progressive course developed a persistent akinetic-mute state, and four of the eight died. Those with the delayed relapsing course either developed a parkinsonian state with behavioral and cognitive impairment but could walk (nine cases), or progressed further to an akinetic-mute state, and were bed-bound (14 cases); the deterioration to either condition occurred rapidly over a few days to a week. Fourteen of the patients with the delayed relapses (61%) subsequently improved, but three (13%) died. Those with a progressive course without initial recovery were younger (mean age, 37.0 years) than those with a delayed relapsing course (55.2 years; p < 0.01). The mean duration of their initial coma (9.8 days) was longer than that in delayed relapsing cases (2.0 days; p < 0.01). The mean initial CO hemoglobin level was not different in the two groups. Brain computed tomography (CT) scans were obtained at the onset of sequelae in both groups. Ten patients had a normal CT scan, 13 had white matter low-density lesions, and four had globus pallidus low-density lesions.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7990851 TI - Superficial hemosiderosis of the central nervous system. AB - Superficial hemosiderosis (SH) of the CNS is a rare disease caused by repeated subarachnoid hemorrhage, with progressive superficial siderosis of the CNS. We report a patient with SH whose clinical picture was marked by progressive gait ataxia, hearing loss, dysarthria, and recurrent episodes of hemifacial spasm. Iron and ferritin levels in the CSF were significantly higher than in a control group of patients. Six month's treatment with the iron-chelating agent trientine dihydrochloride led to clinical improvement, with a concomitant reduction of CSF iron level. We suggest that, in addition to magnetic resonance imaging findings, CSF levels of iron and ferritin should be used as diagnostic criteria for SH, as well as to estimate the efficacy of iron chelation treatment. PMID- 7990852 TI - Visual thresholds to low-contrast pattern displacement, color contrast, and luminance contrast stimuli in Parkinson's disease. AB - We used the computerized Moorfield Vision System to demonstrate specific increases in various perceptual visual thresholds in idiopathic Parkinson's syndrome. Fifteen patients were compared to 13 age-matched normals. Motion detection was impaired maximally (2 p < 0.01 and better in two-tailed t test) at luminance contrasts of 3-7%. Stimulus was an achromatic vertical 4 cycles/degrees sine wave grating subtending 3 degrees x 2 degrees, centered 5 degrees in the nasal field and oscillating at 5 Hz. In addition, stationary color and luminance contrast thresholds were tested with flashed display of 5 degrees x 6 degrees random letters, which were presented for 200 ms (color) and 50 ms (achromatic). Color discrimination was impaired in the tritan axis only (2 p < 0.05 in two tailed t test). All achromatic stimuli--luminance increments, decrements, and phase reversing stimuli--were equally well seen by patients and controls. We conclude that the dopaminergic deficit of retinal amacrine cells in Parkinson patients can be monitored by combined low-contrast and motion (displacement) stimuli. Future studies will determine if moving colored targets are more effective in discriminating patients from controls than are the achromatic gratings used in this work. PMID- 7990853 TI - Propriospinal myoclonus: evidence for spinal "pattern" generators in humans. AB - The clinical and electrophysiological characteristics of eight patients with propriospinal myoclonus are described. Myoclonus developed within days or weeks of cervical trauma in half the patients. Seven cases had axial flexion jerks, and one axial extension jerks. Myoclonic EMG activity consisted of repetitive bursts with a frequency of 1-7 Hz. The jerks in three of the cases were comprised of alternating and rhythmic bursts of EMG activity in rectus abdominis and the paraspinal muscles. From these new observations, it is proposed that cervical trauma can lead to the partial release of a spinal pattern generator. The latter is capable of recruiting muscles through long propriospinal pathways into complex rhythmic activity. PMID- 7990854 TI - Motor effects of the partial dopamine agonist (-)-3-(3-hydroxyphenyl)-N-n propylpiperidine (preclamol) in Parkinson's disease. AB - The motor effects of the partial dopamine agonist (-)-3-(3-hydroxyphenyl)-N-n propylpiperidine [(-)-3-PPP, preclamol] were evaluated in nine patients with Parkinson's disease using a double-blind, placebo-controlled design. (-)-3-PPP monotherapy had an antiparkinsonian effect in five of nine patients at a mean dose of 37 +/- 10 mg intramuscularly. The co-administration of (-)-3-PPP and a mildly dyskinetic dose of levodopa, infused intravenously at steady-state, resulted in complete suppression of dyskinesias and reemergence of parkinsonian signs in two of seven patients. These dopamine antagonist effects of (-)-3-PPP occurred at relatively low (2.5 and 5 mg) doses. Our results suggest that partial dopamine agonists can exert agonist or antagonist activity in parkinsonian patients depending on concurrent dopaminergic tone. Although this dual action of (-)-3-PPP and other partial agonists could be therapeutically important on theoretical grounds, the small number of patients manifesting a clinically significant response and the frequently inconsistent effects could indicate that this class of agents may have relatively limited clinical utility. PMID- 7990855 TI - First emergence of "delayed-on" and "dose failure" phenomena in a patient with Parkinson's disease following vagotomy. PMID- 7990856 TI - Ataxic hemiparesis. PMID- 7990857 TI - Parkinson's disease and milacemide. PMID- 7990858 TI - Clastogenicity of methapyrilene hydrochloride in cultured Chinese hamster cells. AB - The antihistaminic agent methapyrilene hydrochloride (MPH, CAS No. 135-23-9) has been reported as a potent rat hepatocarcinogen. However, neither the action mechanism nor mutagenicity of MPH have been clearly elucidated yet. Chromosomal aberration (CA) tests were performed with MPH in CHO-K1-BH4 and CHL cells without a metabolic activation system. Isochromatid break-like aberrations were observed in metaphases of CHO-K1-BH4 cells treated with MPH. MPH induced CA more effectively at higher pH in equitoxicity base. In contrast to CHO-K1-BH4 cells, typical chromatid type exchanges were observed in CHL cells treated with MPH. These results clearly support the results of other researchers that MPH induce chromosomal aberration and imply that MPH induces cancer in animal via other mechanisms than mere DNA damage or gene mutation which had been nearly proven to be negative by many researchers. It was suggested that pH variation might increase the sensitivity of CA tests for certain category of chemicals with dissociation potential. PMID- 7990859 TI - Dexamethasone, granisetron, or both for the prevention of nausea and vomiting during chemotherapy for cancer. AB - BACKGROUND: Serotonin-receptor antagonists seem to be as effective as corticosteroids in preventing emesis induced by moderately emetogenic antineoplastic agents. We compared the antiemetic effect of a combination of granisetron and dexamethasone with that of granisetron or dexamethasone administered alone. METHODS: From December 1992 to January 1994, 482 consecutive patients who were to receive moderately emetogenic chemotherapy for the first time (600 to 1000 mg of cyclophosphamide per square meter of body-surface area, > or = 50 mg of doxorubicin per square meter, > or = 75 mg of epirubicin per square meter, or > or = 300 mg of carboplatin per square meter, alone or in some combination) were enrolled in a double-blind, randomized, multi-center study evaluating the efficacy and toxicity of three antiemetic regimens. The following antiemetic regimens were used: 8 mg of dexamethasone given intravenously before chemotherapy plus 4 mg given orally immediately before chemotherapy and then every six hours for a total of four doses, 3 mg of granisetron given intravenously before chemotherapy, or a combination of granisetron and dexamethasone given in the doses used for the single-drug regimens. RESULTS: We evaluated 408 patients (136 receiving dexamethasone, 137 receiving granisetron, and 135 receiving both drugs). In the first 24 hours after chemotherapy, complete protection from vomiting and complete protection from nausea were achieved in 70.6 and 55.1 percent, respectively, of the patients receiving dexamethasone, in 72.3 and 48.2 percent of those receiving granisetron, and in 92.6 and 71.9 percent of those receiving granisetron combined with dexamethasone (P < 0.001 for all comparisons). Patients who received granisetron alone had less protection from delayed vomiting and nausea than those who received dexamethasone alone or the two drugs combined. All the regimens were equally well tolerated. CONCLUSION: Granisetron combined with dexamethasone was the most effective regimen for the prevention of emesis induced by moderately emetogenic chemotherapy. PMID- 7990860 TI - Association of Epstein-Barr virus with leiomyosarcomas in young people with AIDS. AB - BACKGROUND: Children with the acquired immunodeficiency syndrome (AIDS) have an unusually high incidence of smooth-muscle tumors (leiomyomas and leiomyosarcomas) in addition to malignant lymphomas. We tested the hypothesis that the smooth muscle tumors in these children are associated with the Epstein-Barr virus (EBV). METHODS: Tissue specimens of five leiomyosarcomas and two leiomyomas from six children with AIDS were studied for evidence of the human immunodeficiency virus (HIV) and EBV by in situ hybridization and quantitative polymerase chain reaction (PCR). Comparison specimens included samples of leiomyosarcoma and leiomyoma from HIV-negative children. EBV clonality of leiomyosarcomas was determined by Southern blot analysis with oligonucleotide probes for EBV terminal-repeat fragments. Tumor specimens were tested by immunoperoxidase staining for infiltration by B lymphocytes and expression of the EBV receptor. Serologic testing for EBV was performed. RESULTS: In situ hybridization showed EBV genomes in all muscle cells of the five leiomyosarcomas and the two leiomyomas from the six HIV-infected children. Quantitative PCR demonstrated strikingly high levels of EBV in tumor tissue, with as many as 4.3 genome copies per cell. Two colonic leiomyosarcomas obtained from different sites at different times from one patient contained different episomal EBV clones, signifying the presence of distinct monoclonal EBV-related tumors. We found biclonal EBV infection in the leiomyosarcoma of another patient. No EBV was detected in normal muscle or tumor specimens from HIV-negative patients. Immunostaining for the EBV receptor was strongly positive in six of the seven leiomyomas and leiomyosarcomas from the patients with AIDS. CONCLUSIONS: EBV can infect smooth-muscle cells, at least in patients with AIDS, and it may contribute to the pathogenesis of leiomyomas and leiomyosarcomas in children with AIDS. EBV seems to play no part in smooth-muscle tumors in HIV-negative children. PMID- 7990861 TI - The association of Epstein-Barr virus with smooth-muscle tumors occurring after organ transplantation. AB - BACKGROUND: Epstein-Barr virus (EBV) has been associated with nasopharyngeal carcinoma, some lymphomas, and lymphoproliferative disease after organ transplantation. Many lymphoproliferative tumors that occur after transplantation are clonal, a property that classifies them as neoplastic. Clonality can be determined by analysis of the extrachromosomal circular DNA episomes produced by EBV infection. METHODS: We describe three young children in whom smooth-muscle tumors developed 18 months to 5 1/2 years after liver transplantation with immunosuppression. We examined the tumors by microscopy and with immunohistochemical studies and molecular genetic analyses of the EBV DNA: RESULTS: The tumors were composed of spindle cells with smooth-muscle features and resembled those described in patients with the acquired immunodeficiency syndrome. Immunohistochemical analysis was negative for EBV latent membrane protein and EBV receptor (CD21), but positive for EBV nuclear antigen 2. In situ hybridization revealed nuclear EBV sequences, and molecular genetic analysis showed the EBV genome to be clonal in all three patients. CONCLUSIONS: Smooth muscle tumors that developed after organ transplantation contained clonal EBV, suggesting that the virus has a role in the development of these neoplastic lesions. PMID- 7990862 TI - Images in clinical medicine. Enterococcus faecalis. PMID- 7990863 TI - Prevention of infective endocarditis. PMID- 7990864 TI - Molecular medicine. Transcription factors. PMID- 7990865 TI - Clinical problem-solving. Pain in the marriage. PMID- 7990866 TI - The next transformation in the delivery of health care. PMID- 7990867 TI - Vision without sight. PMID- 7990868 TI - Epstein-Barr virus--an old dog with new tricks. PMID- 7990869 TI - The genetic basis of dwarfism. PMID- 7990871 TI - The use of placebo controls. PMID- 7990870 TI - Suppression of melatonin secretion in some blind patients by exposure to bright light. AB - BACKGROUND: Complete blindness generally results in the loss of synchronization of circadian rhythms to the 24-hour day and in recurrent insomnia. However, some blind patients maintain circadian entrainment. We undertook this study to determine whether some blind patients' eyes convey sufficient photic information to entrain the hypothalamic circadian pacemaker and suppress melatonin secretion, despite an apparently complete loss of visual function. METHODS: We evaluated the input of light to the circadian pacemaker by testing the ability of bright light to decrease plasma melatonin concentrations in 11 blind patients with no conscious perception of light and in 6 normal subjects. We also evaluated circadian entrainment over time in the blind patients. RESULTS: Plasma melatonin concentrations decreased during exposure to bright light in three sightless patients by an average (+/- SD) of 69 +/- 21 percent and in the normal subjects by an average of 66 +/- 15 percent. When two of these blind patients were tested with their eyes covered during exposure to light, plasma melatonin did not decrease. The three blind patients reported no difficulty sleeping and maintained apparent circadian entrainment to the 24-hour day. Plasma melatonin concentrations did not decrease during exposure to bright light in seven of the remaining blind patients; in the eighth, plasma melatonin was undetectable. These eight patients reported a history of insomnia, and in four the circadian temperature rhythm was not entrained to the 24-hour day. CONCLUSIONS: The visual subsystem that mediates light-induced suppression of melatonin secretion remains functionally intact in some sightless patients. The absence of photic input to the circadian system thus constitutes a distinct form of blindness, associated with periodic insomnia, that afflicts most but not all patients with no conscious perception of light. PMID- 7990872 TI - The use of placebo controls. PMID- 7990873 TI - The use of placebo controls. PMID- 7990874 TI - The use of placebo controls. PMID- 7990875 TI - The use of placebo controls. PMID- 7990876 TI - The use of placebo controls. PMID- 7990877 TI - The use of placebo controls. PMID- 7990878 TI - The use of placebo controls. PMID- 7990879 TI - The use of placebo controls. PMID- 7990880 TI - More on Chlamydia pneumonia and meningoencephalitis. PMID- 7990881 TI - The risk of breast cancer after giving birth. PMID- 7990882 TI - Surgery for breast cancer. PMID- 7990883 TI - Health care and the homeless. PMID- 7990884 TI - Health care and the homeless. PMID- 7990885 TI - Case records of the Massachusetts General Hospital. Weekly clinicopathological exercises. Case 1-1995. An elderly man with a questionable bronchial carcinoid tumor of long duration and recently increasing tracheal obstructions. PMID- 7990886 TI - Low birth weight--not a black-and-white issue. PMID- 7990887 TI - ACE inhibition in acute myocardial infarction. PMID- 7990889 TI - Cost-effectiveness analyses. PMID- 7990888 TI - MHC class II regulation--lessons from a disease. PMID- 7990890 TI - Cost-effectiveness analyses. PMID- 7990891 TI - Cost-effectiveness analyses. PMID- 7990892 TI - Cost-effectiveness analyses. PMID- 7990893 TI - Cost-effectiveness analyses. PMID- 7990894 TI - Clinical problem-solving: invasive interventions. PMID- 7990895 TI - Clinical problem-solving: invasive interventions. PMID- 7990896 TI - Clinical problem-solving: invasive interventions. PMID- 7990897 TI - Clinical problem-solving: invasive interventions. PMID- 7990898 TI - Clinical problem-solving: invasive interventions. PMID- 7990899 TI - Cyclosporine in severe ulcerative colitis. PMID- 7990900 TI - Lithium in the treatment of mood disorders. PMID- 7990901 TI - Expression of P antigen in parvovirus B19-infected bone marrow. PMID- 7990902 TI - PCR and the misdiagnosis of active tuberculosis. PMID- 7990903 TI - Prevalence of low birth weight and preterm delivery in relation to the interval between pregnancies among white and black women. AB - BACKGROUND: The higher mortality rate among black infants than among white infants in the United States results largely from the greater frequency of low birth weight and prematurity among black infants. Higher rates of low birth weight and preterm delivery have been associated with shorter intervals between pregnancies. METHODS: We studied a racially mixed population of women in military families, who had access to free, high-quality health care. A total of 1992 white and black women had two consecutive, singleton pregnancies during the study period. We determined the outcome of the second of each pair of pregnancies and the length of time between the pregnancies. RESULTS: Short interpregnancy intervals (calculated from delivery to the next conception) were more frequent among black than among white women. A total of 7.7 percent of the 298 black women and 3.2 percent of the 1628 white women delivered premature, low-birth-weight infants (P < 0.001). Among the black women, an interpregnancy interval of less than nine months was associated with a significantly greater prevalence of preterm delivery and low birth weight in the neonates (11.6 percent, vs. 4.4 percent for longer interpregnancy intervals; P = 0.020). Among the white women, only intervals of less than three months between pregnancies were associated with a greater prevalence of prematurity and low birth weight in the infants (11.8 percent vs. 2.8 percent; P < 0.001). Of the black women, 46.3 percent had interpregnancy intervals of less than nine months; 4.2 percent of the white women had interpregnancy intervals of less than three months. CONCLUSIONS: A short interval between pregnancies is a risk factor for low birth weight and preterm delivery, and such intervals are more common among black than among white women. The relative frequency of intervals of less than nine months between pregnancies may be an important factor in the wide disparity in pregnancy outcomes between white and black women in the United States. PMID- 7990904 TI - The effect of the angiotensin-converting-enzyme inhibitor zofenopril on mortality and morbidity after anterior myocardial infarction. The Survival of Myocardial Infarction Long-Term Evaluation (SMILE) Study Investigators. AB - BACKGROUND: Left ventricular dilatation and neuroendocrine activation are common after acute anterior myocardial infarction. Long-term treatment with an angiotensin-converting-enzyme (ACE) inhibitor may improve outcome by attenuating these processes. We investigated whether the ACE inhibitor zofenopril, administered for six weeks after anterior myocardial infarction, could improve both short-term and long-term outcome. METHODS: A total of 1556 patients were enrolled within 24 hours after the onset of symptoms of acute anterior myocardial infarction, and they were randomly assigned in a double-blind fashion to receive either placebo (784 patients) or zofenopril (772 patients) for six weeks. At this time we assessed the incidence of death or severe congestive heart failure. The patients were reexamined after one year to assess survival. RESULTS: The incidence of death or severe congestive heart failure at six weeks was significantly reduced in the zofenopril group (55 patients, 7.1 percent), as compared with the placebo group (83 patients, 10.6 percent); the cumulative reduction in the risk of death or severe congestive heart failure was 34 percent (95 percent confidence interval, 8 to 54 percent; P = 0.018). The reduction in risk was 46 percent (95 percent confidence interval, 11 to 71 percent; P = 0.018) for severe congestive heart failure and 25 percent (95 percent confidence interval, -11 to 60 percent; P = 0.19) for death. After one year of observation, the mortality rate was significantly lower in the zofenopril group (10.0 percent) than in the placebo group (14.1 percent); the reduction in risk was 29 percent (95 percent confidence interval, 6 to 51 percent; P = 0.011). CONCLUSIONS: Treatment with zofenopril significantly improved both short-term and long-term outcome when this drug was started within 24 hours after the onset of acute anterior myocardial infarction and continued for six weeks. PMID- 7990905 TI - Brief report: twin boys with major histocompatibility complex class II deficiency but inducible immune responses. PMID- 7990906 TI - Images in clinical medicine. Fungus ball. PMID- 7990907 TI - Tuberculosis among health care workers. PMID- 7990908 TI - More patent troubles about genes. AB - Two decisions by the British Appeal Court raise questions about the allowable breadth of biotechnology patents, but point to the charges patent-holders should be free to make. PMID- 7990909 TI - House of Lords is asked to rule on breadth of gene patent coverage. PMID- 7990910 TI - NIH 'should rethink pricing clause'. PMID- 7990911 TI - As US bans 'embryos for research'. PMID- 7990913 TI - Prospects grow brighter for global biosafety agreement. PMID- 7990912 TI - Fetal gene therapy under the microscope... PMID- 7990914 TI - AIDS summit promises left hanging. PMID- 7990915 TI - Cancer agency denies mismanagement. PMID- 7990916 TI - Cycles of growth and destruction. PMID- 7990917 TI - Developmental neurobiology. Death of a synapse. PMID- 7990918 TI - Signal transduction. Dorsal developments. PMID- 7990919 TI - Demography. Killing the sex ratio. PMID- 7990920 TI - Nitric oxide. More jobs for that molecule. PMID- 7990921 TI - Fullerenes in Allende meteorite. PMID- 7990922 TI - How molecular motors work. AB - What is the molecular basis of cell movement and changes in cell shape? The integration of three approaches is revealing how the molecular motors that drive these processes move and produce force. PMID- 7990923 TI - Long-term synapse loss induced by focal blockade of postsynaptic receptors. AB - Focal application in vivo of alpha-bungarotoxin to block neurotransmission in a small region of a neuromuscular junction causes long-lasting synapse elimination at that site. In contrast, blockade of neurotransmission throughout a junction does not cause synapse elimination. These and related experiments indicate that active synaptic sites can destabilize inactive synapses in their vicinity. PMID- 7990924 TI - Campomelic dysplasia and autosomal sex reversal caused by mutations in an SRY related gene. AB - Induction of testis development in mammals requires the presence of the Y chromosome gene SRY. This gene must exert its effect by interacting with other genes in the sex-determination pathway. Cloning of a translocation chromosome breakpoint from a sex-reversed patient with campomelic dysplasia, followed by mutation analysis of an adjacent gene, indicates that SOX9, an SRY-related gene, is involved in both bone formation and control of testis development. PMID- 7990925 TI - A high-resolution image of atomic hydrogen in the M81 group of galaxies. AB - It has long been recognized that interactions between galaxies are important in determining their evolution. The distribution of gas--out of which new stars are formed--is strongly affected; in particular, gas may be concentrated near the nucleus, leading to a burst of star formation. Here we present a map of atomic hydrogen (H I) in the nearest interacting group of galaxies (that dominated by M81), obtained by combining 12 separate fields observed with the Very Large Array. The H I that surrounds M81, M82 and NGC3077 (the most prominent galaxies in the group) is dominated by filamentary structures, clearly demonstrating the violent disruption of this system by tidal interactions. These observations should have detected all H I complexes more massive than 10(6) solar masses, meaning that our map contains all structures that might evolve into new dwarf galaxies. PMID- 7990926 TI - Combined spatial and temporal imaging of brain activity during visual selective attention in humans. AB - Visual-spatial attention is an essential brain function that enables us to select and preferentially process high priority information in the visual fields. Several brain areas have been shown to participate in the control of spatial attention in humans, but little is known about the underlying selection mechanisms. Non-invasive scalp recordings of event-related potentials (e.r.ps) in humans have shown that attended visual stimuli are preferentially selected as early as 80-90 ms after stimulus onset, but current e.r.p. methods do not permit a precise localization of the participating cortical areas. In this study we combined neuroimaging (positron emission tomography) with e.r.p. recording in order to describe both the cortical anatomy and time course of attentional selection processes. Together these methods showed that visual inputs from attended locations receive enhanced processing in the extrastriate cortex (fusiform gyrus) at 80-130 ms after stimulus onset. These findings reinforce early selection models of attention. PMID- 7990927 TI - Drug excretion mediated by a new prototype of polyspecific transporter. AB - Cationic drugs of different types and structures (antihistaminics, antiarrhythmics, sedatives, opiates, cytostatics and antibiotics, for example) are excreted in mammals by epithelial cells of the renal proximal tubules and by hepatocytes in the liver. In the proximal tubules, two functionally disparate transport systems are involved which are localized in the basolateral and luminal plasma membrane and are different from the previously identified neuronal monoamine transporters and ATP-dependent multidrug exporting proteins. Here we report the isolation of a complementary DNA from rat kidney that encodes a 556 amino-acid membrane protein, OCT1, which has the functional characteristics of organic cation uptake over the basolateral membrane of renal proximal tubules and of organic cation uptake into hepatocytes. OCT1 is not homologous to any other known protein and is found in kidney, liver and intestine. As OCT1 translocates hydrophobic and hydrophilic organic cations of different structures, it is considered to be a new prototype of polyspecific transporters that are important for drug elimination. PMID- 7990928 TI - Systemic and mucosal immunity induced by BCG vector expressing outer-surface protein A of Borrelia burgdorferi. AB - The bacillus Calmette-Guerin (BCG) is a live attenuated strain of Mycobacterium bovis which offers potential advantages as a vector for mucosal delivery of antigens. Recombinant BCG elicits protective humoral immune responses to a variety of antigens. Furthermore, BCG binds specifically to microfold cells present in the epithelium overlying lymphoid follicles throughout the mucosal immune system. Here we show that a single intranasal vaccination with recombinant BCG expressing the outer-surface protein A antigen from B. burgdorferi results in a prolonged (more than one year) protective systemic IgG response and a highly sustained secretory IgA response which is disseminated throughout the mucosal immune system. Furthermore, intranasal immunization induces marked, organized lymphocyte accumulation in the proximal nasopharyngeal lymphoid tissue as well as at distal mucosal sites; the appearance and persistence of lymphoid aggregates correlates with the secretory immune responses. Thus intranasal immunization with recombinant BCG is a powerful method for inducing long-lasting secretory and systemic immune responses. PMID- 7990929 TI - Locus-specific somatic hypermutation in germinal centre T cells. AB - Somatic hypermutation and affinity-driven selection of active immunoglobulin genes occur in germinal centres (GCs), resulting in the generation of high affinity memory B cells. In contrast, T lymphocytes do not require the germinal centre microenvironment to establish memory and the T-cell antigen receptor (TCR) genes, though homologous to immunoglobulin genes, are believed to be incapable of hypermutation. Here we present direct evidence that the small population of antigen-specific T cells that are recruited into splenic GCs acquire mutations in the variable region of genes encoding TCR alpha-chains (V alpha) but not those of beta-chains. These locus-specific mutations reach frequencies comparable to mutated immunoglobulin VH exons recovered from the same site and exhibit similar substitution biases and DNA strand polarity. T cells bearing identical mutations appear in multiple GCs, raising the possibility that some cells bearing mutant TCRs may re-enter the peripheral lymphocyte pool. PMID- 7990930 TI - Decreased sensitivity to tumour-necrosis factor but normal T-cell development in TNF receptor-2-deficient mice. AB - Tumour necrosis factor (TNF) elicits multiple biological effects through two distinct cell surface receptors, TNF-R1 (p55) and TNF-R2 (p75). Most TNF-mediated biological responses, such as cell death, gene induction, antiviral activity and cytokine production, have been attributed to TNF-R1 (refs 1-5). Gene targeting of this receptor confirms its role in the lethality attributable to low doses of lipopolysaccharide after sensitization with D-galactosamine; surprisingly, the toxicity of high doses of lipopolysaccharide was unaffected. The function of TNF R2 is less well understood, although there are data supporting a role in T-cell development and the proliferation of cytotoxic T lymphocytes. To clarify the physiological role of TNF-R2, we have generated mice deficient in this receptor by gene targeting. The TNF-R2-/- mice show normal T-cell development and activity, but we find that they have increased resistance to TNF-induced death. Additionally, such mice injected subcutaneously with TNF show a dramatic decrease in tissue necrosis, indicating that this receptor plays a role in the necrotic effects of TNF. PMID- 7990931 TI - A yeast gene necessary for bud-site selection encodes a protein similar to insulin-degrading enzymes. AB - Cells of the yeast Saccharomyces cerevisiae choose bud sites in a non-random spatial pattern that depends on mating type: axial for haploid cells and bipolar for a/alpha diploid cells. We identified a mutant yeast, axl 1, in which the budding pattern is altered from axial to bipolar. Expression of the AXL1 gene is repressed in a/alpha diploid cells. With the ectopic expression of AXL1, a/alpha cells exhibited an axial budding pattern, thus AXL1 is a key morphological determinant that distinguishes the budding pattern of haploid cells from that of a/alpha diploid cells. AXL1 encodes a protein similar in sequence of the human and Drosophila insulin-degrading enzymes and to the Escherichia coli ptr gene product. The axial budding pattern might result from degradation of a target protein by the putative Axl1 protease. PMID- 7990933 TI - Coalition pursues ban on animals in teaching. PMID- 7990934 TI - Biodiversity treaty nations to study biosafety protocol. PMID- 7990932 TI - Interleukin-2-mediated elimination of the p27Kip1 cyclin-dependent kinase inhibitor prevented by rapamycin. AB - The cyclin-dependent kinase (Cdk) enzymes, when associated with the G1 cyclins D and E, are rate-limiting for entry into the S phase of the cell cycle. During T cell mitogenesis, antigen-receptor signalling promotes synthesis of cyclin E and its catalytic partner, Cdk2, and interleukin-2 (IL-2) signalling activates cyclin E/Cdk2 complexes. Rapamycin is a potent immunosuppressant which specifically inhibits G1-to-S-phase progression, leading to cell-cycle arrest in yeast and mammals. Here we report that IL-2 allows Cdk activation by causing the elimination of the Cdk inhibitor protein p27Kip1, and that this is prevented by rapamycin. By contrast, the Cdk inhibitor p21 is induced by IL-2 and this induction is blocked by rapamycin. Our results show that p27Kip1 governs Cdk activity during the transition from quiescence to S phase in T lymphocytes and that p21 function may be restricted to cycling cells. PMID- 7990936 TI - . . . as tighter research links urged. PMID- 7990935 TI - Row over industry link-up splits staff of Spanish lab. PMID- 7990937 TI - UN AIDS chief will 'mobilize' commitment... PMID- 7990938 TI - Alas, poor title. PMID- 7990940 TI - Remarkable and novel increase. PMID- 7990939 TI - Randomization. PMID- 7990941 TI - Training for Africans in Africa. PMID- 7990942 TI - Science for art's sake. AB - Hollywood's absent-minded professor, always a cliche, is now more unrealistic than ever before. Just how can biological research move forward in the modern era? PMID- 7990944 TI - Peer review: a call for help. PMID- 7990943 TI - Exploiting a medical tradition. PMID- 7990945 TI - Institute living on its wits. PMID- 7990946 TI - Clinical efficiency. PMID- 7990947 TI - Bootstrapping a new institute. PMID- 7990948 TI - Neuropsychology. Faces, fear and the amygdala. PMID- 7990949 TI - Translation. Knowing when to stop. PMID- 7990950 TI - Pharmacology. Endogenous cannabinoids. PMID- 7990951 TI - Human genetics. Silence speaks in spectrin. PMID- 7990952 TI - Protein superfamilies and domain superfolds. AB - As the protein sequence and structure databases expand rapidly a better understanding of the relationships between proteins is required. A classification is considered that extends the sequence-based superfamilies to include proteins with similar function and three-dimensional structures but no sequence similarity. So far there are only nine protein folds known to recur in proteins having neither sequence nor functional similarity. These folds dominate the structure database, representing more than 30 per cent of all determined structures. This observation has implications for protein-fold recognition. PMID- 7990953 TI - An unusual member of the nuclear hormone receptor superfamily responsible for X linked adrenal hypoplasia congenita. AB - X-linked adrenal hypoplasia congenita is a developmental disorder of the human adrenal gland that results in profound hormonal deficiencies and is lethal if untreated. We have isolated the gene responsible for the disease, DAX-1, which is deleted or mutated in X-linked adrenal hypoplasia patients. DAX-1 encodes a new member of the nuclear hormone receptor superfamily displaying a novel DNA-binding domain. The DAX-1 product acts as a dominant negative regulator of transcription mediated by the retinoic acid receptor. PMID- 7990955 TI - Conformation of GroEL-bound alpha-lactalbumin probed by mass spectrometry. AB - The conformation of a three-disulphide derivative of bovine alpha-lactalbumin bound to the molecular chaperone GroEL has been investigated by monitoring directly its hydrogen exchange kinetics using electrospray ionization mass spectrometry. The bound protein is weakly protected from exchange to an extent closely similar to that of an uncomplexed molten globule state of the three disulphide protein. Binding to GroEL in this system appears to involve relatively disordered partly folded states resembling intermediates formed in the very early stages of kinetic folding of many proteins in vitro. PMID- 7990954 TI - In vivo repression by a site-specific DNA-binding protein designed against an oncogenic sequence. AB - A DNA-binding peptide comprising three zinc-fingers has been engineered to bind specifically to a unique nine-base-pair region of a BCR-ABL fusion oncogene in preference to the parent genomic sequences. Binding to the target oncogene in chromosomal DNA is possible in transformed cells in culture, and results in blockage of transcription. Consequently, murine cells rendered independent of growth factors by the action of the oncogene revert to factor dependence upon transient transfection with a vector expressing the peptide. PMID- 7990956 TI - Record of fluid-rock interactions on Mars from the meteorite ALH84001. AB - Allan Hills (ALH) 84001 is the most recently recognized member of a suite of meteorites--the SNCs--that almost certainly originated on Mars. Several factors distinguish ALH84001 from the other SNC meteorites. Preliminary studies suggest that it may be older than other martian meteorites. Moreover, it contains abundant, zoned domains of calcium-iron-magnesium carbonate that are indigenous to the sample and thus may hold important clues regarding near-surface processes on Mars and the evolution of the martian atmosphere. We report here analyses of the carbon and oxygen stable-isotope compositions of the carbonates that place constraints on their formation conditions. Our results imply the presence of at least two chemically distinct carbonates--one Ca,Fe-rich, the other Mg-rich--that are enriched in 13C relative to terrestrial carbonates (delta 13C approximately +41/1000), consistent with martian atmospheric CO2 as the carbon source. The oxygen isotope compositions of the carbonates indicate that they precipitated from a low-temperature fluid in the martian crust. Combined with textural and bulk geochemical considerations, the isotope data suggest that carbonate deposition took place in an open-system environment in which the ambient temperature fluctuated. PMID- 7990957 TI - Impaired recognition of emotion in facial expressions following bilateral damage to the human amygdala. AB - Studies in animals have shown that the amygdala receives highly processed visual input, contains neurons that respond selectively to faces, and that it participates in emotion and social behaviour. Although studies in epileptic patients support its role in emotion, determination of the amygdala's function in humans has been hampered by the rarity of patients with selective amygdala lesions. Here, with the help of one such rare patient, we report findings that suggest the human amygdala may be indispensable to: (1) recognize fear in facial expressions; (2) recognize multiple emotions in a single facial expression; but (3) is not required to recognize personal identity from faces. These results suggest that damage restricted to the amygdala causes very specific recognition impairments, and thus constrains the broad notion that the amygdala is involved in emotion. PMID- 7990958 TI - Mutations in the DAX-1 gene give rise to both X-linked adrenal hypoplasia congenita and hypogonadotropic hypogonadism. AB - Adrenal hypoplasia congenita (AHC) is an X-linked disorder characterized by primary adrenal insufficiency. Hypogonadotropic hypogonadism (HHG) is frequently associated with this disorder but is thought not to be caused by the low adrenal androgen levels due to adrenal hypoplasia. It is uncertain whether there are two distinct yet physically linked genes responsible for AHC and HHG or a single gene responsible for both diseases. AHC can occur as a part of a contiguous deletion syndrome together with Duchenne muscular dystrophy (DMD) and/or glycerol kinase deficiency (GKD). From the analysis of deletions, the following gene order has been deduced: Xpter-AHC-GKD-DMD-cen. An AHC critical region of 200-500 kilobases has been defined by physical mapping and partially overlaps with a 160-kilobase dosage-sensitive sex (DSS) reversal critical region. The DAX-1 (DSS-AHC critical region on the X, gene 1) gene was isolated and found to encode a new member of the nuclear hormone receptor family. Here we report that DAX-1 is deleted in 14 patients and point mutations were found in the coding region in DNA from 12 unrelated individuals. All AHC patients over 14 years old and with only point mutations in DAX-1 were also diagnosed with HHG, confirming that the DAX-1 gene is responsible for both X-linked AHC and HHG. But in four sporadic cases and a single familial case, no point mutations were found, suggesting genetic heterogeneity or differential expression of DAX-1. PMID- 7990959 TI - Role of the LIM class homeodomain protein Xlim-1 in neural and muscle induction by the Spemann organizer in Xenopus. AB - Like all known LIM class homeobox genes, Xlim-1 encodes a protein with two tandemly repeated cysteine-rich LIM domains upstream of the homeodomain. In Xenopus laevis, Xlim-1 is specifically expressed in the Spemann organizer, whose major functions include neural induction and dorsalization of ventral mesoderm. From RNA injection experiments we conclude here that: (1) the LIM domains behave as negative regulatory domains; (2) LIM domain mutants of Xlim-1 elicited neural differentiation in animal explants; (3) mutant, and to a lesser extent wild-type, Xlim-1 enhanced muscle formation after coinjection with Xbra; (4) both of these activities are mediated by extracellular signals as seen in combined explant experiments; (5) Xlim-1 mutants activated goosecoid (gsc) expression in animal explants, but not expression of noggin or follistatin; (6) mutant Xlim-1 elicited formation of partial secondary axes, and cooperated with gsc in notochord formation. Thus Xlim-1 has latent activities, implicating it in organizer functions. PMID- 7990960 TI - Epithelial transformation of metanephric mesenchyme in the developing kidney regulated by Wnt-4. AB - The kidney has been widely exploited as a model system for the study of tissue inductions regulating vertebrate organogenesis. Kidney development is initiated by the ingrowth of the Wolfian duct-derived ureteric bud into the presumptive kidney mesenchyme. In response to a signal from the ureter, mesenchymal cells condense, aggregate into pretubular clusters and undergo an epithelial conversion generating a simple tubule. This then undergoes morphogenesis and is transformed into the excretory system of the kidney, the nephron. We report here that the expression of Wnt-4, which encodes a secreted glycoprotein, correlates with, and is required for, kidney tubulogenesis. Mice lacking Wnt-4 activity fail to form pretubular cell aggregates; however, other aspects of mesenchymal and ureteric development are unaffected. Thus, Wnt-4 appears to act as an autoinducer of the mesenchyme to epithelial transition that underlies nephron development. PMID- 7990961 TI - The signalling molecule BMP4 mediates apoptosis in the rhombencephalic neural crest. AB - The pattern of skeletal structures and muscles in the branchial region of the head is profoundly influenced by the neural crest, whose cells arise at discrete segmental levels of the chick hindbrain: specifically, rhombomeres (r)1+2, r4 and r6, whereas r3 and r5 are crest-depleted. We have demonstrated that an interaction between even-numbered rhombomeres and r3/r5 effects this depletion of neural crest, resulting in the sculpting of discrete migratory streams of neural crest. This mechanism acts through increased expression of msx2 and the induction of apoptosis in dorsal cells of r3 and r5 (ref. 3) (Fig. 1A). Here we demonstrate that the signalling molecule Bmp4 is expressed in r3 and r5 and is dependent on the neighbouring rhombomeres. Addition of recombinant BMP4 protein to explant cultures of r3 or r5, which produce neural crest when isolated from their neighbouring rhombomeres, upregulates msx2 and reinstates apoptosis in the neural crest population. PMID- 7990962 TI - Formation and inactivation of endogenous cannabinoid anandamide in central neurons. AB - Anandamide (N-arachidonoyl-ethanolamine) was recently identified as a brain arachidonate derivative that binds to and activates cannabinoid receptors, yet the mechanisms underlying formation, release and inactivation of this putative messenger molecule are still unclear. Here we report that anandamide is produced in and released from cultured brain neurons in a calcium ion-dependent manner when the neurons are stimulated with membrane-depolarizing agents. Anandamide formation occurs through phosphodiesterase-mediated cleavage of a novel phospholipid precursor, N-arachidonoyl-phosphatidylethanolamine. A similar mechanism also governs the formation of a family of anandamide congeners, whose possible roles in neuronal signalling remain unknown. Our results and those of others indicate therefore that multiple biochemical pathways may participate in anandamide formation in brain tissue. The life span of extracellular anandamide is limited by a rapid and selective process of cellular uptake, which is accompanied by hydrolytic degradation to ethanolamine and arachidonate. Our results thus strongly support the proposed role of anandamide as an endogenous neuronal messenger. PMID- 7990963 TI - A potent peptidomimetic inhibitor of HSV ribonucleotide reductase with antiviral activity in vivo. AB - Herpes simplex viruses (HSV) types 1 and 2 encode their own ribonucleotide reductases (RNRs) (EC 1.17.4.1) to convert ribonucleoside diphosphates into the corresponding deoxyribonucleotides. Like other iron-dependent RNRs, the viral enzyme is formed by the reversible association of two distinct homodimeric subunits. The carboxy terminus of the RNR small subunit (R2) is critical for subunit association and synthetic peptides containing these amino-acid sequences selectively inhibit the viral enzyme by preventing subunit association. Increasing evidence indicates that the HSV RNR is important for virulence and reactivation from latency. Previously, we reported on the design of HSV RNR inhibitors with enhanced inhibitory potency in vitro. We now report on BILD 1263, which to our knowledge is the first HSV RNR subunit-association inhibitor with antiviral activity in vivo. This compound suppresses the replication of HSV-1, HSV-2 and acyclovir-resistant HSV strains in cell culture, and also strongly potentiates the antiviral activity of acyclovir. Most importantly, its anti herpetic activity is shown in a murine ocular model of HSV-1-induced keratitis, providing an example of potent nonsubstrate-based antiviral agents that prevent protein-protein interactions. The unique antiviral properties of BILD 1263 may lead to the design of new strategies to treat herpesvirus infections in humans. PMID- 7990964 TI - Ypt1p implicated in v-SNARE activation. AB - Synaptobrevin-like membrane proteins that reside on transport vesicles, called the vesicle SNARE (v-SNARE), play a key role in ensuring that a vesicle targets and fuses with its correct acceptor compartment. Here we show that Bos1p, the v SNARE of yeast endoplasmic reticulum-to-Golgi transport vesicles, pairs with another integral membrane protein of similar topology (Sec22p) on vesicles. This pairing, which appears to require functional Ypt1p (Rab in mammalian cells), may aid the activity of Bos1p on this compartment. These findings suggest that Rabs regulate the specificity of membrane fusion by selectively activating the v-SNARE on carrier vesicles. Because the v-SNARE resides on more than one membrane, such a regulated activation step may be necessary to prevent the premature fusion of donor and acceptor compartments. PMID- 7990965 TI - A highly conserved eukaryotic protein family possessing properties of polypeptide chain release factor. AB - The termination of protein synthesis in ribosomes is governed by termination (stop) codons in messenger RNAs and by polypeptide chain release factors (RFs). Although the primary structure of prokaryotic RFs and yeast mitochrondrial RF is established, that of the only known eukaryotic RF (eRF) remains obscure. Here we report the assignment of a family of tightly related proteins (designated eRF1) from lower and higher eukaryotes which are structurally and functionally similar to rabbit eRF. Two of these proteins, one from human and the other from Xenopus laevis, have been expressed in yeast and Escherichia coli, respectively, purified and shown to be active in the in vitro RF assay. The other protein of this family, sup45 (sup1) of Saccharomyces cerevisiae, is involved in omnipotent suppression during translation. The amino-acid sequence of the eRF1 family is highly conserved. We conclude that the eRF1 proteins are directly implicated in the termination of translation in eukaryotes. PMID- 7990966 TI - Structure of the human ADP-ribosylation factor 1 complexed with GDP. AB - ADP-ribosylation factors (ARFs) are essential and ubiquitous in eukaryotes, being involved in vesicular transport and functioning as an activator of phospholipase D (refs 1, 2) and cholera toxin. The functions of ARF proteins in membrane traffic and organelle integrity are intimately tied to its reversible association with membranes and specific interactions with membrane phospholipids. One common feature of these functions is their regulation by the binding and hydrolysis of GTP. Here we report the three-dimensional structure of full-length human ARF1 (M(r) 21,000) in its GDP-bound non-myristoylated form. The presence of a unique amino-terminal alpha-helix and loop, together with differences in Mg2+ ligation and the existence of a non-crystallographic dimer, set this structure apart from other GTP-binding proteins. These features provide a structural basis for the GTP dependent modulation of membrane affinity, the lack of intrinsic GTPase activity, and the nature of effector binding surfaces. PMID- 7990967 TI - Effects of metal cations on [3H]alpha,beta-methylene ATP binding in rat vas deferens. AB - In this study we have examined the effect of metal cations (as their chloride salts) on the binding of [3H]alpha,beta-methylene ATP ([3H]alpha beta meATP) to rat vas deferens membranes using a vacuum filtration receptor binding assay. Whereas NaCl and KCl (0.01 and 30 mM) did not affect total binding of 1 nM [3H]alpha beta meATP, several divalent and trivalent cation salts markedly increased binding. The trivalent cation salts, FeCl3 and AlCl3 (0.1 to 100 microM), produced the greatest increases in total binding of [3H]alpha beta meATP, however, their effects were most probably due to precipitation of the radioligand. In contrast, several divalent cations, at concentrations between 1 microM and 1-10 mM, increased total binding of [3H]alpha beta meATP to rat vas deferens by between 87% and 215% while having no effect on either filter binding or non specific binding. The following pEC50 values for potentiating binding of the radioligand were obtained: ZnCl2 (5.44), MnCl2 (4.52), CaCl2 (4.17), CoCl2 (4.06), MgCl2 (3.67) and BaCl2 (3.10). Both EDTA and EGTA (0.01-1 mM) inhibited the binding of the radioligand. The effects of ZnCl2, CaCl2 and MgCl2 were examined in saturation studies. In the absence of added divalent cations, [3H]alpha beta meATP labelled both high (pKd = 9.15) and low (pKd = 7.06) affinity binding sites. The affinity of the radioligand for its high affinity sites was increased by 3 mM CaCl2 (pKd = 9.56) and by 30 microM ZnCl2 (pKd = 9.46) but not by 3 mM MgCl2. The Bmax of the low affinity site for [3H]alpha beta meATP was increased (approximately 4 fold) by both 3 mM MgCl2 and 30 microM ZnCl2 but not by 3 mM CaCl2. The selective effect of CaCl2 on the high affinity binding sites enabled these sites to be labelled in the presence of 3 mM CaCl2 using a low concentration of [3H]alpha beta meATP (1 nM); the sites exhibited the binding characteristics expected of the P2x purinoceptor. The selective effect of MgCl2 on the low affinity binding sites enabled these sites to be labelled in the presence of 3 mM MgCl2 and using a high concentration of [3H]alpha beta meATP (100 nM). A comparison of the binding characteristics of the high and low affinity sites for [3H]alpha beta meATP revealed several other differences, in addition to their cation selectivity.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 7990968 TI - Corelease of noradrenaline and ATP by brief pulse trains in guinea-pig vas deferens. AB - Contractions and overflow of tritium and ATP elicited by single electrical pulses or short pulse trains were studied in the guinea-pig isolated vas deferens preincubated with [3H]-noradrenaline. ATP was measured using the luciferase technique. A single pulse caused only a small contraction and minimal tritium and ATP overflow. In contrast, trains of 6 pulses elicited marked contractions as well as tritium and ATP overflow. In experiments with 6 pulses/100 Hz, prazosin 0.3 microM reduced the contraction by 73%, did not change the evoked overflow of tritium, and reduced the evoked overflow of ATP by 85%. Suramin 300 microM reduced the contraction by 69% but changed neither the evoked overflow of tritium nor that of ATP. The combination of prazosin 0.3 microM and suramin 300 microM abolished the contraction, did not change the evoked overflow of tritium, and reduced the evoked overflow of ATP by 70%. When 6 pulses were applied at frequencies of 1, 2, 10 or 100 Hz, all responses increased with frequency up to a maximum at 10 Hz, but contractions and the evoked overflow of ATP increased with frequency to a greater extent than the evoked overflow of tritium. A similar frequency overflow relationship was observed when the medium contained prazosin 0.3 microM and suramin 300 microM (and evoked ATP overflow was greatly reduced). Yohimbine 1 microM did not affect the overflow of tritium evoked by 6 pulses/100 Hz but increased that evoked by 6 pulses/10 Hz. The results demonstrate an overflow of both noradrenaline and ATP in response to short pulse trains.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7990969 TI - Uptake of 3H-catecholamines by rat liver cells occurs mainly through a system which is distinct from uptake1 or uptake2. AB - Isolated rat hepatocytes were incubated with 200 nmol/l 3H-(-)-noradrenaline or 50 nmol/l 3H-(-)-adrenaline for 15 min, in Krebs-Henseleit solution at 37 degrees C, gassed with 95% O2 5% CO2. Monoamine oxidase and catechol-O-methyl transferase were inhibited with pargyline (500 mumol/l) and Ro 01-2812 (3,5 dinitropyrocatechol; 2 mumol/l), respectively. Total radioactivity present in the cells, which corresponded mostly to intact 3H-amine, was measured. The content of 3H-noradrenaline increased with time of incubation, a plateau having been reached after 15 min of incubation. After 15 min of incubation, the cell: medium ratio for 3H-noradrenaline and 3H-adrenaline was 0.6-0.7. Desipramine (an inhibitor of the neuronal uptake of catecholamines-uptake1; 1 mumol/l) did not affect the uptake of either 3H-noradrenaline or 3H-adrenaline into hepatocytes. Corticosterone (an inhibitor of the extraneuronal uptake of catecholamines uptake2; 40 mumol/l) slightly inhibited (by 28%) the uptake of 3H-adrenaline, and did not significantly reduce 3H-noradrenaline uptake. Probenecid (an inhibitor of the renal transport of organic anions; 100 mumol/l) did not influence the amount of either 3H-noradrenaline or 3H-adrenaline in hepatocytes. Cyanine 863 (an inhibitor of the renal transport of organic cations; 10 mumol/l) decreased by 62% the uptake of 3H-adrenaline into cells but did not significantly affect 3H noradrenaline uptake. Bilirubin (a substrate of a hepatic transport for organic anions; 200 mumol/l) produced a significant increase (50%) in the amount of 3H noradrenaline and 3H-adrenaline present in the cells.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7990970 TI - Comparison of cloned and pharmacologically defined rat tissue alpha 1 adrenoceptor subtypes. AB - Multiple alpha 1-adrenoceptor subtypes have been defined by pharmacological and receptor cloning techniques, but the precise alignment of cloned and pharmacologically-defined subtypes is still unclear. We have compared the affinities of 8 subtype-selective compounds at three cloned alpha 1-adrenoceptor subtypes (rat alpha 1B, bovine alpha 1C, rat alpha 1A/D) with those previously determined by the same methods in rat spleen, cerebral cortex, and kidney (Naunyn Schmiedeberg's Arch. Pharmacol. 348: 385-395, 1993). Among all compounds tested to date at cloned alpha 1-adrenoceptor subtypes (+)-tamsulosin appears to be the most selective with a rank order of potency alpha 1C > alpha 1A/D > or = alpha 1B. Affinities for the alpha 1A-selective 5-methyl-urapidil, methoxamine, oxymetazoline, phentolamine and (-)- and (+)-tamsulosin and for noradrenaline and SDZ NVI-085 at the splenic alpha 1B-adrenoceptors and at their low affinity sites in cerebral cortex and kidney correlated best with those at the cloned alpha 1B adrenoceptor. Affinities of these drugs at their high affinity sites in cerebral cortex (pharmacologically-defined alpha 1A-adrenoceptor) were matched best by those at the cloned alpha 1C-adrenoceptor. Rat kidney appears to contain two chloroethylclonidine-resistant alpha 1-adrenoceptor subtypes one of which is similar to the cloned alpha 1C- and one to the cloned alpha 1A/D-adrenoceptor. We conclude that the cloned alpha 1B-adrenoceptor is the genetic correlate of the pharmacologically-defined alpha 1B-adrenoceptor. An alpha 1-adrenoceptor subtype corresponding to the cloned alpha 1A/D-adrenoceptor appears to exist in rat kidney.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7990971 TI - The effects of sigma ligands on the release of glutamate from rat striatal slices. AB - This study investigated the effects of sigma receptor ligands on the release of endogenous amino acid neurotransmitters from rat striatal slices. The effect of haloperidol on release in slices prepared from 6-hydroxydopamine lesioned animals was also tested. Haloperidol, the (+/-) reduced metabolite of haloperidol, rimcazole and ifenprodil specifically reduced potassium-stimulated release of glutamate with IC50 values between 20-60 microM. The release of aspartate, gamma aminobutyric acid (GABA) and glycine was not affected. Haloperidol also reduced glutamate release from slices prepared from lesioned animals. The neuroleptic drug alpha-flupenthixol and the putative sigma receptor ligand R(+)3-(3 hydroxyphenyl)-N-(n-propyl) piperidine (3-PPP) had no effect on release. These effects of the sigma ligands show that the inhibition of glutamate release is specific to this amino acid and also that it is not due to dopamine receptor blockade as those ligands which have low affinity for dopamine receptors were also effective in reducing release. A presynaptic location for sigma receptor sites, possibly associated with ion channels, could account for the effects of these ligands on transmitter release. PMID- 7990972 TI - Characteristics of tail-tremor induced by nicotine in rats. AB - To characterize the tail-tremor and locomotor hyperactivity induced by repeated nicotine administration, the effects of nicotinic, alpha-adrenergic and dopaminergic blockers were investigated in rats. Daily administration of nicotine (0.5 mg/kg, s.c.) induced tail-tremor from the 4th day, which became more marked in intensity by subsequent administration. Locomotor hyperactivity was also induced by nicotine, which was enhanced by daily administration. The tail-tremor and locomotor hyperactivity induced by repeated nicotine administration were inhibited by mecamylamine (0.1-1 mg/kg, i.p.) but not by hexamethonium (0.5 and 1 mg/kg, i.p.). Clonidine (0.02 and 0.04 mg/kg, i.p.) and prazosin (0.5 and 1 mg/kg, i.p.) reduced tail-tremor more markedly than hyperactivity. However, haloperidol (0.05-0.2 mg/kg, i.p.) and chlorpromazine (1-5 mg/kg, i.p.) reduced hyperactivity more markedly than tail-tremor. These results suggest that nicotine induced tail-tremor and hyperactivity are due to an increased susceptibility of central nicotinic receptors of nicotine followed by catecholaminergic mechanisms, and that tail-tremor may be more associated with the noradrenergic system than the dopaminergic system. PMID- 7990973 TI - Comparison of the cromakalim antagonism and bradycardic actions of a series of novel alinidine analogues in the rat. AB - Alinidine, and eight derivatives, were synthesized and tested for their ability to antagonise the actions of the K+ channel opener cromakalim in rat thoracic aorta, and for their ability to induce bradycardia in rat isolated spontaneously beating right atria. Ring segments of rat thoracic aorta were suspended in organ baths to record isometric tension. Tissues were precontracted with K+ (20 mM), and full concentration-relaxation curves constructed to cromakalim (0.01-30 microM) in the absence and presence of increasing concentrations of alinidine/derivative. The majority of the compounds tested caused rightward shifts in the cromakalim concentration-effect curves. Rat spontaneously beating right atria were suspended in organ baths to record rate of contraction. Addition of alinidine/derivative caused a concentration-dependent negative chronotropic response. In terms of structure-activity relationships, increasing the length of the N-allyl side-chain on the alinidine molecule (from 3 carbon (3C), to 5C) resulted in a significant increase in the activity of the compounds as both bradycardic agents and cromakalim antagonists. The most potent compounds in both cases (bradycardic agent and cromakalim antagonist) had no double bond in the side chain. The results suggest that the carbon side-chain influences the activity of alinidine-related compounds both as cromakalim antagonists and as bradycardic agents. However, while similar structure-activity relationships appear to apply for both effects in some instances, there was no significant correlation between the two actions of the alinidine analogues. The results suggest that the ability of alinidine-derivatives to induce bradycardia or to block K+ channels opened by cromakalim can be differentiated on the basis of structure. PMID- 7990974 TI - A new synthetic antiarrhythmic peptide reduces dispersion of epicardial activation recovery interval and diminishes alterations of epicardial activation patterns induced by regional ischemia. A mapping study. AB - Common antiarrhythmic agents affect ionic membrane channels and thereby alter cellular electrical activity. Since this accounts for the proarrhythmic effects as well we tried to find new substances with different profiles of actions. A new antiarrhythmic peptide, H2N-Gly-Ala-Gly-4 Hyp-Pro-Tyr-CONH2 (AAP 10), was synthetized using the Fmoc-strategy. This peptide was analyzed for its electrophysiological profile of action in normal isolated rabbit hearts perfused according to the Langendorff technique either under control conditions or after induction of a regional ischemia. For this purpose 256 channel epicardial mapping was employed allowing the determination of the timepoints of activation at each electrode thus identifying the origins of epicardial activation (socalled breakthrough-points, BTP). Epicardial spread of activation was then described mathematically by activation vectors which gave direction and velocity of the epicardial activation wave at each electrode. Single heart beats were analyzed under control conditions and under treatment with AAP 10 or under regional ischemia with or without AAP 10-pretreatment (10(-8) mol/l). We calculated the percentage of similar vectors (VEC) with unaltered direction (deviation < or = 5 degrees) and the percentage of identical breakthroughpoints (deviation < or = 1 mm) compared to control conditions. In addition, apparent epicardial velocities, total activation time of a given region and activation-recovery interval (ARI) as well as dispersion of ARI (i.e. standard deviation of ARI) and distribution of ARI were analyzed. Under control conditions treatment with AAP 10 (10(-10) to 3 x 10(-7) mol/l) led to a significant decrease in ARI-dispersion without alteration of any of the other parameters under investigation. Left ventricular regional ischemia resulted in a marked alteration of the activation patterns (a significant decrease in vectorfield- and breakthroughpoint-similarity) which could be significantly inhibited by pretreatment with AAP 10. In addition, we found that AAP 10 depressed the increase in ARI-dispersion during the first minutes of ischemia and accelerated normalization of ARI-dispersion during reperfusion. In additional experiments, it could be shown that AAP 10 did not alter action potential duration, maximum dU/dt, amplitude or resting membrane potential of isolated guinea pig muscles using a common intracellular action potential recording technique.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 7990975 TI - Low dose calcium-antagonism compensates for impaired myocardial blood supply resulting from deficient nitric oxide synthesis. AB - Coronary artery disease (CAD) has been documented to be usually associated with endothelial dysfunction. Thus, the present experiments were performed to investigate whether non-hypotensive doses of calcium antagonists can compensate for the effects of deficient endogenous formation of nitric oxide (NO) in the coronary vascular bed in vivo. In chronically instrumented conscious dogs (n = 6) which were prepared for the measurement of coronary blood flow (CBF), coronary diameter of the left circumflex artery (LCX), mean arterial blood pressure (MAP) and heart rate (HR), continuous intravenous infusions of 0.2 micrograms/kg/min nisoldipine (NI) or 2.0 micrograms/kg/min diltiazem (DT) were performed after intracoronary pretreatment with either vehicle or the inhibitor of NO synthesis NG-nitro-L-arginine methyl ester (L-NAME, 6 mg/kg). NI dose-dependently increased CBF up to a maximum of +74 +/- 7.5% from control, while LCX diameter and HR were not significantly affected. MAP fell slightly (-5 +/- 3 mmHg). The maximum CBF increase in response to diltiazem at 10-fold higher doses was +39 +/- 13% while MAP fell -12 +/- 2 mmHg at the highest cumulative dose (100 micrograms/kg). HR and LCX diameter remained unaltered. Pretreatment with L-NAME caused marked hypertension and bradycardia, associated with reduction in CBF (-34 +/- 16%) and LCX diameter (-9.5 +/- 0.8%). Subsequent infusion of NI or DT increased CBF up to the control values obtained before L-NAME. In contrast, both calcium antagonists failed to reverse the effects on MAP or HR.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7990976 TI - Hypoxia induces release of atrial natriuretic peptide in rat atrial tissue: a role for this peptide during low oxygen stress. AB - A variety of different factors have been shown to induce release of atrial natriuretic peptide from atrial tissue. Among these, stretching of atrial myocytes is considered the most important. In a recent study we showed that atrial natriuretic peptide increased cGMP and reduced lactate accumulation during hypoxia in rat ventricular myocardium. This suggests that atrial natriuretic peptide has a beneficial metabolic effect during hypoxia and raises the question whether hypoxia alone induces release of atrial natriuretic peptide. The right atrium and pieces of the right ventricle, from rats, were incubated in polyethylene vials containing 3 ml Krebs bicarbonate buffer equilibrated with 75% N2 + 20% O2 + 5% CO2 (= hypoxic conditions) or 95% O2 + 5% CO2 (= normoxic conditions). After 10 min, the ventricular tissues and aliquots of the buffer were frozen. Cyclic GMP was analyzed in the ventricular tissue and atrial natriuretic peptide was analyzed in the buffer samples. The results show that the release of atrial natriuretic peptide during hypoxia significantly exceeds the release under normoxic conditions. The hypoxia-induced release of atrial natriuretic peptide over time is characterized by an s-shaped curve with the steepest slope after about 10 min. In the presence of atrial tissue the intracellular level of cGMP in ventricular myocardium increased from 0.3 +/- 0.1 to 2.6 +/- 0.9 pmol/g w wt (P = 0.033, n = 6). We conclude that ANP is released from atrial tissue and induces increased formation of cGMP in ventricular myocardium when oxygen tension is low.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7990977 TI - Effects of neuropeptide Y and vasoactive intestinal peptide on human venous smooth muscle in vivo. AB - The direct and noradrenaline-modulating effects of neuropeptide Y (NPY) and vasoactive intestinal peptide (VIP) on venous smooth muscle were studied in healthy volunteers employing the dorsal hand vein compliance technique. Local infusions of NPY had no measurable effect on venous tone, but coinfusion of a constant high dose of NPY (242 pmol/min) with noradrenaline caused a 2.9-fold increase in the mean ED50 for noradrenaline. The dilating effect of VIP on preconstricted hand veins was weak, maximal venodilation could not be achieved, because systemic side effects occurred at submaximally venodilating doses. Coinfusion of noradrenaline with a weakly venodilating, constant dose of VIP (93.2 pmol/min) caused a 0.5-fold decrease in the sensitivity for noradrenaline. Although functional interactions between NPY or VIP and noradrenaline could be demonstrated, the dosages of the peptides required were high. Thus our results indicate that neither NPY nor VIP exert a major direct or noradrenaline modulating effect on human veins. PMID- 7990978 TI - Bradykinin-induced contraction of guinea pig lung in vitro. AB - We have investigated the contractile effect of bradykinin (BK) in guinea pig lung in vitro. BK induces a dose-related contraction of lung parenchymal strips which is increased significantly in the presence of 10(-5) M captopril (an angiotensin converting enzyme inhibitor) or 10(-5) M DL-thiorphan (a neutral endopeptidase inhibitor). The kininase I inhibitor, DL-2-mercaptomethyl-3-guanidino ethylthiopropionic acid (MGTPA), has no effect on the BK-induced contraction. BK is more potent in contracting parenchymal lung strips than other contractile agents (histamine, carbachol and substance P), however the BK-induced maximal contraction is lower than those obtained with histamine and carbachol. The B1 agonist, des-Arg9-BK, does not contract lung parenchymal strips. The new BK B2 receptor antagonists (Hoe 140, NPC 17731 and NPC 17761), which possess binding affinities in the nanomolar range, inhibit the BK-induced contractile response in a dose-dependent manner. The BK-induced contraction was unaffected by propranolol, atropine, tetrodotoxin, capsaicin pre-treatment, triprolidine, methysergide, Ro 19-3704 and N omega-nitro-L-arginine-methyl-ester (L-NAME), excluding the involvement of nervous pathways, preformed mast cell mediators, platelet-activating factor and nitric oxide. However, indomethacin, a cyclooxygenase inhibitor, AA-861, a 5-lipoxygenase inhibitor, and furegrelate, a thromboxane A2 synthase inhibitor, decreased the contractile response to BK, suggesting that both cyclooxygenase and 5-lipoxygenase products are involved in this contraction.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7990979 TI - Characterization of [3H]brevetoxin binding to voltage-dependent sodium channels in adrenal medullary cells. AB - We have previously reported that in bovine adrenal chromaffin cells Ptychodiscus brevis toxin-3 (PbTx-3) does not alter the veratridine-induced 22Na influx when given alone, but increases the influx of 22Na when co-applied with either alpha- or beta-scorpion venom (Wada et al. 1992). In the present study, we characterized [3H]PbTx-3 binding in bovine adrenal chromaffin cells. [3H]PbTx-3 binding was saturable, reversible and of high-affinity with an equilibrium dissociation constant (Kd) of 32.0 +/- 4.9 nmol/l and a maximum binding capacity (Bmax) of 6.2 +/- 1.2 pmol/4 x 10(6) cells (4.5 +/- 0.9 pmol/mg cell protein). A Hill plot revealed the lack of cooperative interaction among the binding sites. Unlabelled PbTx-3 inhibited [3H]PbTx-3 binding with an IC50 of 31 nmol/l. However, tetrodotoxin, veratridine, alpha- and beta-scorpion venom, or veratridine in combination with either alpha- or beta-scorpion venom did not alter [3H]PbTx-3 binding. All these results suggest that PbTx-3 binds to a site (site 5) distinct from the previously known four toxin binding sites, which does not gate voltage dependent Na channels by itself, but is specifically involved in the allosteric modulation of Na channels in adrenal medullary cells. PMID- 7990980 TI - Structure-activity relationship of covalently dimerized insulin derivatives: correlation of partial agonist efficacy with cross-linkage at lysine B29. AB - The effects of 7 covalently dimerized insulin derivatives on glucose transport in differentiated 3T3-L1 cells were investigated. Symmetric cross-linkage at lysine B29 with a bridge of 2 (oxalyl), 8 (suberoyl) or 12 (dodecanedioyl) carbon atoms produced derivatives with essentially unaltered receptor binding affinity but largely reduced intrinsic activity. Regardless of the chain length, these derivatives inhibited the effect of submaximal insulin concentrations. Insulin derivatives cross-linked at phenylalanine B1 or asymmetrically at B1/B29 were full agonists of the insulin receptor. When lysine B29 was cross-linked with the inactive desoctapeptide(B23-B30)insulin at phenylalanine B1, the intrinsic activity of the resulting dimer was lower than that of insulin, but higher than that of the symmetric B29-dimers. It is concluded that linkage at the B29 lysines, and not at the B1-phenylalanine, leads to partial agonism of dimerized insulin derivatives, regardless of the length of the crosslinker. PMID- 7990982 TI - [Sensitization to hypoallergenic cosmetics]. PMID- 7990981 TI - Regulation of gastric acid secretion by histamine H3 receptors in the dog: an investigation into the site of action. AB - The involvement of histamine H3 receptors in the regulation of gastric acid secretion was investigated in the conscious dog with gastric fistula, by the use of the selective agonist (R)alpha-methylhistamine and the selective antagonist thioperamide. (R)alpha-methylhistamine (0.3-1.2 mumol/kg/h) induced a dose related inhibition of the acid secretion induced by pentagastrin and by bombesin, maximum inhibition not exceeding 60-65%. The inhibitory effect of the H3 agonist (0.6 mumol/kg/h) was inhibited by thioperamide (0.1 mumol/kg/h), suggesting that the effect was entirely mediated by H3 receptors. Thioperamide was also able to enhance the acid response to submaximal doses of pentagastrin and bombesin. The acid secretion induced by histamine was not modified by (R)alpha-methylhistamine (0.3-1.2 mumol/kg/h) but it was significantly enhanced by thioperamide (0.1 mumol/kg/h). Neither (R)alpha-methylhistamine nor thioperamide significantly modified the increase in plasma gastrin levels induced by bombesin. In conclusion these data demonstrate that histamine H3 receptors may represent an effective mechanism for the negative control of stimulated gastric acid secretion in the dog; however, since the inhibition was mainly evident against stimuli which involve the release of histamine, a location of H3 receptors in paracrine cells of the gastric mucosa rather than in gastrin producing cells or parietal cells seems more likely. PMID- 7990983 TI - [The 1994 Nobel Prize for Medicine for the discovery of G-protein]. PMID- 7990984 TI - [Chemotherapy in metastasized breast carcinoma: intermittent or continuous?]. PMID- 7990985 TI - [Role of mucins in inflammatory intestinal diseases]. PMID- 7990986 TI - [Measles in The Netherlands; epidemiology and the effect of vaccination]. AB - OBJECTIVE: To estimate the incidence of measles in the Netherlands and assess the effect of vaccination with regard to vaccination status. DESIGN: Retrospective study. METHOD: Data were collected from the Central Bureau for Statistics (CBS), reported cases at the National Health Department (NHD), data from hospitals concerning admissions, morbidity data from the General Practitioner Networks, serological data from virology laboratories and serological data from several other studies. RESULTS: After introduction of the measles vaccination in 1976, morbidity and reported cases decreased dramatically. Some data suggest that measles in children over 10 years old are reported more frequently. Death caused by measles did not occur after 1988. CONCLUSION: The massive vaccination since 1976 resulted in an initial decrease in incidence of measles. The increase in incidence thereafter was probably caused by an increase in, and crowding of vulnerable, older people. No effect on the severity of the complications were seen so far. Surveillance is necessary to follow groups at risk and to take proper preventive measures. PMID- 7990987 TI - [A measles epidemic in an adequately vaccinated middle school population]. AB - OBJECTIVE: To assess the extent of a measles epidemic in a secondary school. DESIGN: Retrospective and questionnaire investigation. SETTING: Secondary school, Bilthoven. METHOD: Questionnaire followed by laboratory testing for measles and other infectious diseases with exanthema. RESULTS: The response rate was 99% (935/949 pupils, aged 12-21 years, vaccination rate 92%). Seventy-seven students underwent laboratory investigations. Measles virus was isolated in 2 suspected patients. Thirty-three of 37 patients with clinical or laboratory criteria of measles had been vaccinated. Complications of measles were not detected. Infection was also detected in patients with relatively few or atypical symptoms. The protective efficacy of measles vaccine could be determined because the attack rate of the school population was less than 5%. CONCLUSION: Primary failure of the measles vaccine might be the cause of the minor epidemic but the results do not cast doubt on the efficacy of the current measles vaccination programme. PMID- 7990988 TI - [Does a modified vaccination schedule protect better against measles?]. AB - OBJECTIVE: To assess the value of an alternative vaccination programme (VP) with Mumps-Measles-Rubella (MMR) vaccine at the ages of 12 and 15 months compared with the standard VP (MMR at the ages of 14-15 months and 9 years). DESIGN: Cross sectional study. SETTING: The area of activity of the 'Lek and Merwede' Extramural Health Care Department. METHOD: Data from general practitioners (GPs) and from an inquiry among parents of 873 children born in a 1.5 year period (randomly taken among 4500 children) and given the alternative MMR VP, were used. The inquiry took place during a measles epidemic in 1993. A non-response study was also executed among the parents. RESULTS: The response of the GPs was low (14 cases reported by 8 out of 90 GPs). Eighty-two per cent of the parents responded. There was no correlation between (non-)response and the alternative VP. The vaccination was effective and no significant differences between standard and alternative VP were found. CONCLUSION: Vaccination protects against measles. An alternative VP could theoretically be more effective, but because of the excellent results of the standard VP differences could not be detected. PMID- 7990989 TI - [acute dystonias in combined abuse of cocaine and neuroleptics]. AB - A 25-year-old mildly retarded black cocaine user was hospitalized 15 times in 10 years for recurrent maniform psychosis. During the last intake he developed severe dystonia following zuclopenthixol 50 mg and droperidol 10 mg i.m. In view of current knowledge regarding the pathophysiology of acute neuroleptic induced dystonias, this suggests that cocaine may be a risk factor for development of acute dystonia. However, only a few studies with small numbers of patients and/or poor design have been reported. Therefore the conclusion cannot be drawn that an anticholinergic should be added to neuroleptics in patients with cocaine abuse. PMID- 7990990 TI - [Quality assurance of Dutch health research]. PMID- 7990991 TI - [Examination and treatment in hyperparathyroidism]. PMID- 7990992 TI - On the importance of cancer registries. PMID- 7990993 TI - Mail order pharmacy--an emerging dilemma. PMID- 7990995 TI - The promise and challenge of physician profiling. PMID- 7990994 TI - Treatment of heart failure: update 1994. PMID- 7990996 TI - Treatment of humeral diaphyseal nonunions using fibular allograft and compression plating. PMID- 7990997 TI - Newer strategies in the prevention of hyaline membrane disease. PMID- 7990998 TI - Physicians, antitrust laws and health system reform. PMID- 7990999 TI - Atheroembolic renal disease: experience with 22 patients. AB - Atheroembolic renal disease (ARD) following an arteriographic procedure developed in 17 patients over a 107-month period in which 14,998 procedures were performed at two hospitals. The incidence of ARD per arteriographic procedure was 0.1%. A review of all nephrology consults during this same period identified five patients with ARD unrelated to a procedure (spontaneous disease). ARD was diagnosed 5.3 +/- 0.9 weeks following an arteriographic procedure. Patients most likely to be diagnosed with ARD were those recently undergoing arteriography (77%), the elderly (mean 69.9 years), males (73%), Caucasians (95%) and patients with renal insufficiency prior to arteriography. In the patients who had arteriography, the baseline serum creatinine increased significantly from a mean of 3.0 +/- 0.6 mg/dl to 6.6 +/- 1.1 mg/dl at the time of diagnosis (P < .05). The mortality rate of 16 patients who progressed to end stage renal disease was significantly greater (75%) than 6 patients who recovered renal function (17%; P < .05). PMID- 7991000 TI - Intraventricular hemorrhage in the premature infant. AB - In summary, IVH is a frequent occurrence in premature infants and will continue to be seen in practice so long as neonatologists remain successful in keeping these very small babies alive. While the low-grade IVH's are typically self limiting conditions, more profound hemorrhages can have devastating effects on the neonate and initiate a progressive chain of events leading to significant neurodevelopmental morbidity. Early diagnosis and prompt medical management can allow a significant number of children to avoid permanent ventriculoperitoneal shunting. While a large number of these children will require a VP shunt, careful optimization of the child's condition prior to shunting in conjunction with a meticulous surgical technique designed to decrease infection rate allows many of these children to lead essentially normal lives. A team approach involving obstetrical care directed towards prevention of early labor and avoidance of hypoxia and hypercapnia at delivery combined with aggressive management by the neonatologist and early neurosurgical consultation is leading to a more hopeful future for many of these infants. PMID- 7991001 TI - Volvulus, the deadly twist. PMID- 7991002 TI - Arthroscopic ankle fusions utilizing bone marrow and demineralized bone matrix: a case report. PMID- 7991003 TI - [Long-term treatment of affective disorders]. AB - The majority of depressive disorders may be viewed as a recurrent condition with the possibility of a deteriorative effect on the quality of life and productivity. The results of clinical investigations suggest that anti-depressant medication should be continued for a period of 4-6 months after the acute episode has been resolved (continuation therapy). What is more controversial, however, is the view that patients who have fully recovered should continue to receive medication in an attempt to prevent a future episode from taking place (maintenance therapy). Taking into account the results of empirical investigations which have shown that depressive disorders appear to become more severe and potentially refractory with each new episode, it is argued that patients at risk for recurrent episodes should receive a maintenance pharmacotherapy. The present study reviews the rationale and practical guidelines for the long-term treatment of affective disorders. PMID- 7991004 TI - [Depression and aggression in Amish persons]. AB - The Old Order Amish are a conservative, anabaptistic religious community of Swiss origin in the USA. They practise absolute pacifism and lead a life free of hostility and aggression. Depression, however, is as much as three times more frequent in Amish populations. In order to study the possible relationship between hostility and depression, we investigated 43 Amish people, using the Buss Durkee Hostility Inventory and the Beck Depression Inventory. As expected, the total hostility score was significantly lower and the depression score significantly higher in comparison to the normal population. The positive correlation between the two scores (0.45; p < or = 0.002) indicates that the hypothesized reciprocal relationship between hostility and depression is unlikely in the Old Order Amish. PMID- 7991005 TI - [Universal time constants in movements of deaf-blind children]. AB - Most human movements are structured in units consisting of a few seconds. This phenomenon may be based upon an inherent central nervous rhythm. The question of this study was whether the movements of children born deaf and blind are structured in a similar way. On a film cutting table, 233 movements were analyzed frame by frame. It could be confirmed that the movements of deaf and blind children were also structured in temporal units. Differences with non handicapped, however, consist in the fact that these units were shorter and more stereotypic repetitions occurred. The present data are discussed in connection with the processing of momentary information in short term memory and the self stimulation by those deprived of hearing and sight. PMID- 7991006 TI - [The physician's cognition during cardiopulmonary resuscitation of the human]. AB - The cognitions of 20 emergency-physicians while working on a mobile resuscitation unit were examined by means of questionnaire in over 260 situations of resuscitation. A pattern of cognitions could be detected: Emergency physicians appear not to think very much during resuscitation. If there are thoughts, these usually concern the obvious, or what is immediately present in the situation, i.e. the patient or the patient's relatives; repression may also play a role. Cognitions which are reflective of self are rare and only develop late in the situation, depending on the surroundings and the amount of stress. The cognitions concerning the relatives are frequent in those situations with direct physician relative contact. The physicians often report in retrospect having felt compelled to a decision for resuscitation by the presence of the relatives; nevertheless, the decision itself appears to be a result, rather, of their cognitions of the relatives. Distancing by means of cognition was ubiquitously employed as a coping strategy by physicians when in situations which were perceived as not having a positive outcome. Thoughts about "own death" or "about the patient" are specific, however, for certain groups of doctors. Results of the present investigation suggest that physicians have cognitions about relatives during the process of decision making, and cognitions about the patient during the resuscitation manoeuvre. PMID- 7991007 TI - [Frontal and temporal onset of brain atrophy. Clinical and instrumental findings]. AB - We report the cases of a 70-year old man with left temporal brain atrophy and of a 39-year-old man with neuropathologically verified frontal lobe degeneration (FLD) of Non-Alzheimer type. 10 patients with FLD collected during a prospective study on degenerative dementia had more severe volumetric brain changes and less severe quantitative band power changes than a group of matched patients with clinically diagnosed Alzheimer's disease. PMID- 7991008 TI - [Nuclear magnetic resonance tomography findings in obsessive-compulsive disorder]. AB - Eighteen patients with a DSM-III-R diagnosis of obsessive-compulsive disorder (OCD) were imaged by MR and compared to a control group of 18 patients with clinically diagnosed unspecific headaches. Weighted spin-echo sequences were carried out with a 1.5T unit in both axial and coronal planes T1 (TR 700/TE 15 ms) and T2 (TR 2500/TE 15.70). The ferritin distributions in the basal ganglia and in the midbrain were evaluated; in addition, the width of the pars compacta in the midbrain on the basis of the criteria of Braffmann et al. 1988, the widths of the inner subarachnoid spaces on the basis of the ventricular index quotient VIQ (TerBrugge, 1986), and the widths of the outer subarachnoid spaces were conducted. The latter was undertaken by three independent investigators whose results were in agreement with one another. In 12 of the OCD patients (n = 18) there was a total of 25 pathological MRI findings; in the control group there were 6 pathological MRI findings in only 6 of the patients (n = 18). In conclusion pathological changes were found at different locations, but a connection between a specific neuroanatomic system and obsessive-compulsive disorder could not be demonstrated. PMID- 7991009 TI - [Multiple personality disorder. Presentation of 2 cases and a model of the etiology]. AB - Although the syndrome of Multiple Personality Disorder (MPD) has received much interest in the international literature, there have been virtually no professional articles on the topic in German over the last 70 years. This is a report on two cases with nine and 70 persons respectively. Both had undergone severe and prolonged sexual abuse in childhood. Compared with DSM-III-R, the ICD 10 criteria seem to reflect historic reports on alternating personalities rather than recent empirical research on multiple personality. The proposed etiological model postulates that extreme trauma in childhood can result in dissociative vulnerability persisting into adulthood. PMID- 7991010 TI - [Exacerbation of an affective psychosis after terminating a decade of benzodiazepine treatment. Which therapeutic procedure is sensible?]. AB - We report the case of a 61-year old patient with an affective disorder who had been treated with benzodiazepines in low dosages over a 16 year period. This treatment had been prescribed by his physician following several depressive episodes. During this time, the patient remained able to work and exhibited little psychopathological symptomatology. Following discontinuation of medication, however, the depressive phases resumed and were particularly intractable. The clinical implications of this case and the therapeutic strategies for approaching patients with long-term benzodiazepine treatment are discussed. PMID- 7991011 TI - [Drug screening in an Austrian prison]. AB - In the Austrian prison Graz, a randomized group of 64 prisoners (12.5% out of 512 total) was selected to investigate patterns of drug abuse. From this group. 60 consented to drug-screening in urine. While opiates, cocaine, alcohol and amphetamines screened negative, cannabis (in 8.4%) and benzodiazepines (in 20%) had positive results. PMID- 7991012 TI - ["Neuroadaptation" in long-term cannabis abuse. A clinical and electroencephalographic case study]. AB - This report is about electroencephalographic changes in a twenty-eight year old patient with longterm heavy cannabis use. He was admitted to our hospital after he had developed a depressive-apathetic syndrome. Two days after the last cannabis-intake, the patient had recovered from initial psychopathology and his EEG was completely inconspicuous at this day. Some days later however the patient's behavior became increasingly impulsive and unstable, while his EEG showed a marked disturbed regulation of vigilance. In the following weeks his impulsiveness became less and his EEG returned to normal. We suggest that these alterations may reflect a discontinuation of the initial neuroadaption of the central nervous system to the drug. PMID- 7991013 TI - [Guidelines for carrying out application studies in psychopharmacotherapy. "Phase IV Research" Study Group of the Society of Neuropsychopharmacology and Pharmacopsychiatry]. PMID- 7991014 TI - [Severe "late" dystonia after neuroleptic anxiolysis with fluspirilene]. PMID- 7991015 TI - [The dangers of "ecstasy"]. PMID- 7991016 TI - [The psychiatric disorder of Vincent van Gogh]. PMID- 7991017 TI - Henoch-Schonlein nephritis. A disease with significant late sequelae. PMID- 7991018 TI - Augmented expression of interleukin-6 and interleukin-1 genes in the mesangium of IgM mesangial nephropathy. AB - IgM mesangial nephropathy (IgMN) is a common pathologic finding in Taiwanese children with nephrotic syndrome. The hallmarks of IgMN are mesangial hypercellularity and IgM immune complex deposition in the mesangial area. In order to investigate whether the interleukin-6 (IL-6) and interleukin-1 (IL-1) protein production and gene mRNA expression are augmented in the local renal tissue of IgMN, we performed histobiochemical and mRNA studies using an immunopathologic technique and in situ hybridization. We also studied the correlation between urinary IL-6 levels and intensity of IL-6 expression in renal tissue. The results show that 15 cases of IgMN had overexpression with the highest score of both IL-6 and IL-1 proteins and mRNA expression in glomerular mesangial cells and diffuse distribution throughout the glomerular mesangium and capillary, Bowman's capsule, interstitium and renal tubule. In contrast, the patients with minimal change nephrotic syndrome and normal controls failed to show IL-6 and IL-1 mRNA overexpression. The urinary IL-6 levels of the patients with IgMN were highly correlated with the intensity of IL-6 protein expression in renal tissue. The higher the IL-6 overexpression, the higher was the rate of steroid resistance with focal sclerosis. These findings suggest that IL-6 and IL 1 mRNA amplification may play important roles in the pathogenesis of IgMN. The urinary level and degree of overexpression of IL-6 may serve as a prognostic parameter. PMID- 7991019 TI - Cytopathological changes induced by cadmium-exposure in canine proximal tubular cells: a cytochemical and ultrastructural study. AB - A highly sensitive cytochemical method for demonstrating intracellular Cd using 8 hydroxyquinoline was developed and applied in the cytopathological study of primary-cultured renal tubular cells from beagle kidneys. The Cd-8 hydroxyquinoline emitted a yellowish-green fluorescence which first appeared in the cytoplasm within 30 min and in the nucleus about 60-90 min after exposure to 100 mM CdCl2. It was noteworthy that intranuclear Cd was stained in the nucleolar regions. The sensitivity of the cytochemical method for Cd was estimated to be about 1.0 pg Cd/cell. Ultrastructural features of the dead cells were consistent with those of apoptosis. We conclude that Cd absorbed by proximal tubular cells rapidly reaches to the nuclei and affects nuclear as well as cytoplasmic metabolism. PMID- 7991020 TI - Systemic factors and renal hemodynamic effects of high-protein meal versus low protein meal in conscious dogs. AB - The effects of a high-protein (HP) and low-protein (LP) meal on glomerular filtration rate (GFR), effective renal plasma flow (ERPF), and renal vascular resistance (RVR) were examined in conscious dogs. Ingestion of the HP and LP meal produced a temporary increase in systemic hemodynamic parameters due in part to a 'cephalic phase' of sympathetic excitement. However only the HP significantly altered renal hemodynamics, i.e. GFR, ERPF and RVR. Plasma renin activity (PRA), serum aldosterone and plasma atrial natriuretic peptide (ANP) concentrations were not significantly altered by either a HP or LP meal. Of all the serum electrolytes measured, serum Ca2+ concentrations were significantly lower after a HP meal. It would appear that protein-meal-induced changes in renal hemodynamics are independent of changes in systemic hemodynamics. The exact mechanism of action of a HP meal on renal hemodynamics is not clear, but it appears that one mechanism by which a HP meal may alter renal hemodynamics is by altered calcium homeostasis. PMID- 7991021 TI - Cloned cells develop renal cortical collecting tubules. AB - We investigated the development and morphogenesis of stem cells cloned from cultured transformed collecting duct cells of the rabbit in the presence of hepatocyte growth factor/scatter factor (HGF), vitamin A, laminin and transforming growth factors, HGF and vitamin A induced peanut agglutinin (PNA) positivity in nonprincipal cells (PC) but not in PCs, only HGF induced tubule formation. Although HGF induced a tubule-like arrangement in both cell lines, tubules with PNA-positive cells were observed only in non-PC cells incubated with HGF. Vasopressin increased intracellular free calcium in PNA-negative cells but not in PNA-positive cells. Intracellular pH increased in PNA-positive cells but not in PNA-negative cells when gluconate was substituted for Cl in the buffer. Cloned non-PCs were stem cells that developed PC- and IC-like characteristics and formed collecting ducts when incubated with HGF. PMID- 7991022 TI - Peritoneopericardial communication after pericardiocentesis in a patient on continuous ambulatory peritoneal dialysis with dialysis pericarditis. AB - A male patient aged 41 years had dialysis pericarditis with massive pericardial effusion in his 6-year on continuous ambulatory peritoneal dialysis (CAPD). Intensive hemodialysis failed to resolve the pericardial effusion. Pericardiocentesis via a subxiphoid approach was performed with placement of a pigtail catheter for drainage. A communication between peritoneal and pericardial cavities occurred, resulting in the leakage of the peritoneal dialysate into pericardial sac which was confirmed by a 99mTc radionuclide scan. The fistula healed after removal of the catheter and discontinuation of CAPD. We suggest that pericardiocentesis via a subxiphoid approach for pericardial effusion should be cautiously exercised in CAPD cases for fear of peritoneopericardial fistula. PMID- 7991023 TI - Renal microangiopathy in the primary antiphospholipid syndrome: a case report with literature review. AB - We report the case of a 52-year-old male patient with recurrent thrombosis from 'primary antiphospholipid syndrome' who developed renal microangiopathy. Despite anticoagulant therapy with coumadin, serum creatinine progressively increased from 398 to 592 mumol/l and platelets decreased to 43,000. The patient responded to high-dose methylprednisolone and aspirin and the renal function improved. A review of the literature disclosed 4 other cases of association between primary antiphospholipid syndrome and renal microangiopathy. The clinical characteristics of these cases are discussed. PMID- 7991024 TI - Severe skin necrosis associated with heparin in hemodialysis. AB - Skin necrosis is a well-recognized although rare complication of continuous heparin therapy. We report the case of a 66-year-old diabetic woman with end stage renal failure who received intermittent intravenous heparin during hemodialysis. She developed severe necrotic cutaneous ulcers over both legs, with typical histological findings. Thrombocytopenia never occurred but platelet studies demonstrated enhanced aggregation when heparin was added in vitro. Platelet-aggregating immunoglobulins produced in response to heparin can lead to thrombotic events. Thrombocytopenia usually develops prior to the onset of cutaneous lesions, but as in this case, may be absent. Heparin should be discontinued when the condition is recognized. Unfortunately, a poor outcome is frequently observed. PMID- 7991025 TI - Minimal-change nephrotic syndrome associated with renal angiomyolipoma. PMID- 7991026 TI - Detection of hepatitis C virus in dialysate and in blood ultrafiltrate of HCV positive patients. PMID- 7991027 TI - Mannitol-induced acute renal failure. PMID- 7991028 TI - Antiphospholipid syndrome and plasma exchange. PMID- 7991029 TI - Tuberculous interstitial nephritis of the renal graft. PMID- 7991030 TI - Low dose of L-carnitine impairs membrane fragility of erythrocytes in hemodialysis patients. PMID- 7991031 TI - IgA-fibronectin aggregates in IgA nephropathy. PMID- 7991032 TI - Effect of potassium-chelating resins on phosphorus absorption. PMID- 7991033 TI - Facial actinomycosis in a renal transplant patient. PMID- 7991034 TI - Renal amyloidosis and rheumatic heart disease. PMID- 7991035 TI - Beta-2-microglobulin levels of dialysis patients with renal amyloidosis secondary to familial Mediterranean fever. PMID- 7991036 TI - Measurement of calcaneus bone mineral density using the osteoanalyzer model SPXHA 110 in patients receiving hemodialysis. PMID- 7991037 TI - Relationship between serum IgA levels and CD4 subsets in IgA nephropathy. AB - In this study, the relationship between serum levels of IgA (s-IgA) and CD4 subsets in peripheral blood was investigated in patients with IgA nephropathy (IgA N). We have also recently reported that the percentage of CD4+ CD45RA+ cells was significantly decreased in this disease. Serum levels of immunoglobulins (IgG, IgA, IgM) and the percentage of CD4+CD45RA+ cells or CD4+CD45RO+ cells were measured by two-color analysis in blood samples obtained from 45 patients with IgA N, 30 patients with various glomerulonephritides and 30 healthy volunteers. A significant decrease of CD4+ CD45RA+ cells and a significant increase of CD4+CD45RO+ cells were observed in the IgA N group. Moreover, in the IgA N group, s-IgA correlated negatively with the percentage of CD4+CD45RA+ cells and correlated positively with that of CD4+CD45RO+ cells. After 1 and 2 years, the same analyses were serially performed in 15 nonmedicated patients with IgA N. Similar results concerning the relationship between s-IgA and CD4 subsets were obtained both after 1 and 2 years. The percent changes of s-IgA (delta s-IgA) correlated with delta CD4+CD45RO+ cells: r = -0.66483 (p < 0.01) after 1 year, r = -0.69688 (p < 0.01) after 2 years. On the other hand, delta s-IgA correlated with delta CD4+CD45RA+ cells (p < 0.05) after 1 year, but no after 2 years. It was concluded that s-IgA levels strongly correlate with the percentage of CD4+ CD45RO+ cells in peripheral blood, in patients with IgA N. PMID- 7991038 TI - Progression of renal failure in chronic primary glomerular diseases. AB - The rate of progression of renal failure was analyzed in 19 patients with biopsy proven chronic primary glomerular diseases, by the slope (regression coefficient) of the linear regression of reciprocal serum creatinine on time. The relative importance of proteinuria, sex, underlying disease and components of arterial pressure (systolic, diastolic and mean) was tested using stepwise multiple linear regression, the dependent variable being the slope of progression. We found that the only variable significantly related with slopes of progression was arterial pressure. Hypertension was found in 14 of the 19 patients. There was a significant linear relationship (p < 0.05) between mean arterial pressure and slopes of progression. Notwithstanding, the best fit to the data follows a quadratic function (p < 0.001 for mean arterial pressure), which corresponds to a negative parabolic curve. Therefore, either low or high values of mean arterial pressure were associated with faster mean progression rates. Thus, an accurate approach of this relationship fits a nonlinear regression model. PMID- 7991039 TI - Glucose-induced insulin secretion in uremia: role of 1 alpha,25(HO)2-vitamin D3. AB - To evaluate the role and mechanism of action of calcitriol on glucose-induced insulin secretion in uremia, 17 patients with severe chronic renal failure were studied. Glucose metabolism was investigated by the intravenous glucose tolerance test (IVGTT) before and after treatment for 21 days with 0.5 microgram/day of calcitriol and 500 mg/day of calcium (C+Ca) (6 cases) or 0.5 microgram/day of calcitriol alone (C) (11 cases). After these evaluations the patients on C+Ca were shifted to C and 6 patients on C were shifted to C+Ca, and IVGTT was repeated 21 days after the shift. For each test plasma glucose (G), immunoreactive insulin (IRI) and C-peptide (C-p) were measured at -30, 0, 2, 5, 15, 30, 45, 60 min, and baseline plasma values of 1 alpha,25(HO)2-vitamin D3, C terminal parathyroid hormone (PTH-C), intact parathyroid hormone (PTH-I), calcitonin, and serum values of total and ionized calcium were dosed. Also, glucose constant decay (K-G), insulin response (IRI area), C-p production (C-p area), insulinogenic index (IGI) and insulin resistance index (RI) were calculated. A historical group of 21 healthy volunteers formed the normal controls. 1 alpha,25(HO)2-vitamin D3 plasma levels in uremic patients before treatment were significantly lower than normal range. As compared to controls, uremic patients showed significantly lower K-G, IRI area and IGI values and significantly higher RI values. After treatment with C or C+Ca, the insulin response improved significantly at 2 and 5 min and G decrement was more marked at 30, 45 and 60 min.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7991040 TI - Domestic cases of hemorrhagic fever with renal syndrome in the United States. AB - Although serologic studies have identified hantaviral infection in the United States, acute disease has not been recognized. This study describes 3 cases of domestically acquired hemorrhagic fever with renal syndrome (HFRS) in the United States. Infection was due to a local strain of Seoul virus (Baltimore rat virus). A review of the clinical features indicated a mild illness characterized by nausea, vomiting, renal and liver failure similar to HFRS described elsewhere for rat-borne viruses. Follow-up of 2 patients identified persistent hypertension and renal disease providing further evidence of an association between past hantaviral infection and hypertensive renal disease. PMID- 7991041 TI - Low-dose simvastatin is a well-tolerated and efficacious cholesterol-lowering agent in ciclosporin-treated kidney transplant recipients: double-blind, randomized, placebo-controlled study in 40 patients. AB - The high prevalence of hypercholesterolemia in kidney transplant recipients probably contributes to the high cardiovascular mortality in these patients. Except for diet, there is no generally recommended cholesterol-lowering treatment. We conducted a double-blind, randomized, placebo-controlled study with low-dose simvastatin in 40 ciclosporin (CS)-treated kidney transplant recipients during 16 weeks, focusing on side effects and dose finding. In the simvastatin group, the mean serum total and LDL cholesterol concentrations decreased by 23 and 33%, respectively, and the mean serum HDL cholesterol concentration increased by 12%, after 4 weeks of treatment with simvastatin 10 mg daily. Increasing the dose to 20 mg daily in a few patients only resulted in marginal further reductions of the serum cholesterol concentrations at the expense of doubling the plasma simvastatin 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitory activity concentrations. The differences between the changes in the serum cholesterol concentrations in the simvastatin group and the negligible changes in the placebo group were statistically significant. There was no case of proximal myopathy and the serum creatine kinase concentrations did not differ between treatment groups. In conclusion, low-dose simvastatin appears to be a well tolerated and efficacious cholesterol-lowering treatment in CS-treated kidney transplant recipients. Simvastatin 10 mg daily seems to be the most suitable dose for the majority of these patients. PMID- 7991042 TI - Outcome and prognostic determinants in the hemolytic uremic syndrome of children. AB - The late outcome in 89 children with the hemolytic-uremic syndrome (HUS) observed from 1971 to 1988 was analyzed up to 17 years after onset in relationship to various clinical and pathologic features at the onset of the disease. In the first 3 months after onset (acute phase) 69% of all children needed dialysis therapy. Fifteen children died, 9 during the acute phase and 6 subsequently. All surviving patients except 7 were reexamined and divided into five prognostic categories: recovery, residual renal symptoms with normal kidney function, moderate renal insufficiency, preterminal chronic renal failure (CRF) and end stage renal disease (ESRD). The rate of recovery calculated by the life table method increased from 35% after 10 years in 1971-1979 to 68% in 1980-1988 (p < 0.001); it was lower in infants than in older children (44 vs. 63%; nonsignificant). Children with atypical HUS experienced more often preterminal CRF, ESRD or death than those with a typical (postenteropathic) form (33 vs. 17%; p < 0.05). If oliguria lasted < 7 days, 74% of patients recovered after 10 years versus 13% in the case of oliguria > 14 days or anuria > 7 days (p < 0.0005). The rate of recovery was also significantly smaller with the duration of dialysis treatment > 7 days, central nervous system involvement and requirement for antihypertensive therapy. In the entire series 7 patients developed preterminal CRF and 5 ESRD. Of 27 cases serially followed for 5-10 years after onset, a stable course was noted in 16, a subsequent improvement in 8 and deterioration in 3 leading to ESRD in 2.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7991043 TI - Enhanced volume-sensitive K flux in patients on chronic hemodialysis. AB - Swelling-activated K flux was investigated in erythrocytes from patients on regular hemodialysis. K influx, measured by 86Rb uptake, was increased in hemodialysis patients from 25.5 +/- 0.6 to 47.3 +/- 3.4 nmol/10(9) cells/h (n = 4, p < 0.01), when the medium osmolarity of Hepes buffer was decreased by 100 mosm/kg H2O. In normal subjects, K influx was also stimulated from 28.1 +/- 1.2 to 37.8 +/- 2.1 nmol/10(9) cells/h (n = 4, p < 0.01). The swelling-activated increment of K influx was comparatively higher in hemodialysis patients (85.5 vs. 34.5% in controls). Reduction of the medium osmolarity by 100 mosm/kg H2O also caused a larger increase of K efflux in hemodialysis patients than in control subjects (171.1 vs. 118.1%). K efflux was increased even in the presence of 10( 4) M ouabain (from 284 +/- 25 to 879 +/- 122 nmol/10(9) cells/h), although the increment of K efflux was completely abolished when Cl was replaced by gluconate (555 +/- 47 nmol/10(9) cells/h with Cl and 467 +/- 44 nmol/10(9) cells/h without Cl). These data suggest that in hemodialysis patients, swelling-activated K transport is enhanced via activation of the Cl-dependent ouabain-insensitive K transport pathway. PMID- 7991044 TI - Salvage of clotted jugular vein hemodialysis catheters. AB - Jugular venous catheters (JVC) provide rapid, vascular access for both emergency and maintenance hemodialysis in both acute and end-stage renal disease. Clotting and occlusion of JVC is a common problem necessitating alternate vascular access. Urokinase will declot 80-90% of central venous catheters; however, recurrence of catheter occlusion is frequent. We successfully employed a guide wire insertion technique to salvage occluded JVC after failed urokinase infusion. In 24 patients JVCs, inserted for either temporary or permanent vascular access, clotted within 6-55 days of initiating hemodialysis. Urokinase (5,000 IU) instilled into both arterial and venous limbs of the catheter had been unsuccessful in restoring patency. In these patients, we inserted a soft-tipped guide wire into both lumina. In 21 of 24 patients (87.5%), guide wire insertion opened the occluded JVC, permitting immediate initiation of hemodialysis. We conclude that for clotted JVC unresponsive to urokinase infusion, guide wire insertion can salvage most catheters thereby facilitating hemodialysis. PMID- 7991045 TI - Effect of renal diseases and comorbid conditions on survival in chronic dialysis patients. AB - International and geographical differences in the survival rates of chronic dialysis patients can be explained by differences in primary renal disease, in the acceptance rate of elderly patients, and in predialysis comorbid conditions. Several studies have shown the effects of these factors on survival. However, in most studies, a large number of patients may leave for renal transplantation or transfer to other centers, so that precise analysis becomes impossible. Although the number of patients in our registry is not so large (n = 1,982), we have few such problems and were able to examine the effects of the above-mentioned factors on patient survival using the Cox proportional hazard model. Hazard ratios (HR) and 95% confidence intervals were 0.739 and 0.366-1.491 in patients with polycystic kidney disease (n = 38), 2.669 and 1.513-4.708 in patients with systemic lupus erythematosus (n = 39), 1.245 and 0.935-1.660 in patients with nephrosclerosis (n = 122), 1.815 and 1.447-2.229 in patients with diabetes mellitus (n = 374), and 1.595 and 1.201-2.117, respectively, in patients with other renal diseases (n = 146) when the HR in patients with chronic glomerulonephritis (n = 1,263) was taken as 1.00. HR and 95% confidence intervals were 1.222 and 1.016-1.470 in patients with one comorbid condition (n = 217) and 1.494 and 1.033-2.160, respectively, in patients with two comorbid conditions (n = 24) when the HR of patients with no predialysis comorbid conditions (n = 1,741) was taken as 1.00. Our data demonstrate the effects of renal diseases and number of predialysis comorbid conditions on the survival in chronic dialysis patients.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7991046 TI - Retinoic acid enhances the number of epidermal growth factor receptors in rat glomerular epithelial cells in vitro. AB - The renal epithelium appears to be an important target tissue for retinoic acid and epidermal growth factor (EGF). We report here that retinoic acid enhances the proliferative effect of EGF on glomerular epithelial cells (GEC) in vitro and also increases EGF binding to GEC. When GEC were exposed to EGF (> or = 1 ng/ml), cellular DNA synthesis was markedly increased. Moreover, the stimulating effect of EGF was synergistically increased by retinoic acid at 5 micrograms/ml. 125I EGF binding to cultured GEC was increased approximately 3-fold after addition of retinoic acid to cultures for 48 h. Analysis of 125I-EGF binding revealed 8.1 x 10(4) receptors per control (untreated) cell, while retinoic acid-treated cells demonstrated an increase to 14.3 x 10(4) receptors per cell with no detectable change in receptor affinity. These findings suggest that interactions between retinoic acid and EGF may play an important role in the regulation of GEC growth. PMID- 7991047 TI - [Vertigo: its clinical and electrophysiological correlations]. AB - In 41 cases of vertigo without abnormalities in neurological examinations BAEP examination, specialistic otological examination, X-ray of the cervical spine were done. In most cases Doppler USG examination of the carotid and vertebral arteries and EEG and CT of the head were obtained. The most frequent abnormality in these examinations were changes in cervical spine found in 30 cases (90%) and in BAEP--36.5%. BAEP changes were most frequently found in patients with known factors for dizziness--41.2%, followed by those with CT changes--33.3%, cervical spine changes--28.6% and changes in USG of the arteries supplying the brain from the neck. PMID- 7991048 TI - [Sleep disorders in patients with brain stem lesions]. AB - In 10 patients with clinical symptoms of brainstem lesions of various aethiology and different localization within the brainstem polysomnographic records were performed. Patients were divided into two groups (according to age) and the results obtained in each group were compared with the results in control group. In all patients prolongation of I and III+IV phases and reduction of II and the REM phase were noted. In some patients REM was not observed at all. These results may confirm the theory of the localization of the sleep centre in the brainstem, specially the centre of induction of the REM. PMID- 7991049 TI - [Assessment of anaerobic metabolism in central nervous system tissues in infants with intractable hypertension]. AB - Analogously to the blood lactate levels in conditions caused by impairment of peripheral circulation the authors sought a correlation between the concentrations of lactate, glucose and lactate dehydrogenase in the cerebrospinal fluid in children with hydrocephalus and the values of intracranial pressure as an important factor impairing oxygen supply to central nervous system tissues. PMID- 7991050 TI - [Peripheral nerve regeneration by autografts in rats. II. Electrophysiological assessment]. AB - Peripheral nerves repairing using freeze-thawed skeletal muscle autografts were compared to conventional nerve grafts with respect to their electrical properties. It was found that the amplitude and distal latency of action potentials in both groups were not significantly different 3 and 6 months after the operation. These observations support the thesis that peripheral nerve repair by freeze-thawed autogenous muscle grafts may have a significant role in the reconstruction of injured nerves. PMID- 7991051 TI - [Assessment of early psychic dysfunctions due to metallic mercury]. AB - The aim of the study was to find the most sensitive psychological test battery, useful for evaluation of the earliest dysfunctions in workers exposed to metallic mercury (Hg). To assess the above mentioned disorders, six tests of interference and four tests of motor reactions were applied. The examinations were performed in 44 male workers exposed to Hg in the process of acetic aldehyde synthesis. The control group was matched for sex, age and educational level. The obtained results showed that in the detection od early dysfunctions of the nervous system, psychological tests of interference are more useful than test of the motor reactions. This toxicological test battery can be recommended for monitoring workers exposed to metallic mercury. PMID- 7991052 TI - [The picture of visual evoked potentials in Kimmerle anomaly]. AB - Visual evoked potentials (VEP) were studied in 16 persons with radiological confirmed Kimmerle anomaly. Each eye was stimulated by the reversible checker board pattern using the reversal and flash stimulation methods. Abnormal responses were noted in about 75% of the studied patients. Latency disturbances prevailed during reversal stimulation and abnormal configuration of responses predominated during flash stimulation. PMID- 7991053 TI - [Iron and transferrin in the blood serum of the patients with acute cerebral vascular disease]. AB - The purpose of this study was to determine the ferrokinetics in patients suffering from acute cerebral vascular diseases by assaying the iron and transferrin levels in the blood serum. Studies were performed on 80 patients. Also a single estimation of the haemoglobin level and of the red blood cell counts were performed in each patient. The iron level in the blood serum was assayed by photocolorimetry, while the level of transferrin was tested by radial immunodiffusion technique. The obtained results were analysed statistically by t Student test. The accepted significance level was p < 0.05. In all groups of stroke patients a decrease of the average iron level and increase of the average transferrin level in the blood serum was found. It can be explained by the general disorders of the metabolism during the course of acute cerebral vascular disorders and feed-back mechanism. PMID- 7991054 TI - [Operative treatment of deep arteriovenous malformations]. AB - The authors present 12 patients operated upon for arteriovenous malformations located in deep structures of brain. In terms of the location, clinical course and neurological status there were three distinct groups of patients. The results of the operative treatment lead to the conclusion that the operative treatment risk is no greater than in cases of superficial AVMs, in which it is generally accepted. PMID- 7991056 TI - [Results of ophthalmological investigations in patients with intracranial aneurysms late after ligation of the common carotid artery]. AB - In the Ophthalmology Department, Medical Academy in Bialystok control examinations of 17 patients aged 48-65 years were carried out late after ligation of the common carotid artery for intracranial aneurysm. The control group comprised 10 patients with such aneurysms not treated surgically. Using ophthalmodynamometry (Sobanski method) reduction was found of the pressure in the central artery of the retina on the side of the ligated artery as compared to the contralateral eye and control group. Besides that, impairment of the visual functions was demonstrated in these cases, related probably to haemodynamic disturbances in the visual system following ligation of the common carotid artery. PMID- 7991055 TI - [Familial occurrence of intracranial aneurysms]. AB - Four cases of intracranial aneurysms are reported found in two families. They accounted for 1% of all patients with these aneurysms treated in that time period. The aetiology of the aneurysms, the most frequent locations in familial cases and the risk of occurrence of asymptomatic aneurysms in such families are discussed. PMID- 7991057 TI - [Giant cell tumors of vertebral column]. AB - Between 1962 and 1993 were treated at the Department of Neurosurgery, Medical Academy in Poznan 11 patients (10 women and 1 man) with giant-cell tumours of the spine. Their mean age was (26.27 +/- 17.56) years. In all patients pain was the presenting symptom and 10 had neurological deficits. The cervical, thoracic and lumbo-sacral spine was involved; 9 patients were treated surgically and 3 patients received adjuvant radiotherapy. The follow-up time was from 2 months to 30 years. PMID- 7991058 TI - [An internal fixator for posterior application to short segments of thoracic, lumbar and lumbosacral spine. Design and testing]. AB - The authors present preliminary experiences in spinal instrumentation with internal fixator Socon (Aesculap). The device was introduced into the routine clinical practice in the Department in 1992. Basing on personal experience they confirm the advantages of usage of internal fixators in spinal surgery especially good stabilisation of the spine and possibility of early mobilisation of patients. Analysis of the series of 6 cases operated on in the Department with the longest follow-up of 10 months revealed no neurological or vascular complication related to pedicle screw insertion, no wound infection and no instability of instrumented segment of the spine. The report includes 3 illustrative cases operated on in the Department. PMID- 7991059 TI - [Diagnosis of Wilson disease by methods of molecular genetics]. AB - Wilson's disease is an inborn error of cooper metabolism, inherited as an autosomal recessive gene. According to the variety of clinical features (most frequency hepatic, neurological, psychiatric and haematological) the clinical diagnostics often meets a number of difficulties. It is important to establish the diagnosis in the pre-symptomatic period, because treatment can prevent developing of the disease. The diagnosis is usually established after biochemical blood tests, that is the serum cooper and ceruloplasmin, 24-hour urinary cooper excretion and the functional test with radioactive cooper. However, all the methods quite frequently do not make it possible to confirm or exclude the diagnosis in sporadic cases. Sometimes, it is also impossible to distinguish between preclinical homozygotes and heterozygotes. Localizing of the pathogenic gene on the long arm of chromosome 13 opens new diagnostic prospects. Still, it is essential to find genetic markers situated next to the gene for applying the linkage analysis. It will also help to isolate the gene and to establish the primary biochemical defect of the disease. PMID- 7991060 TI - [Physiological basis and clinical relevance of brain temperature control]. AB - It has been recently shown that small variations in cerebral temperature critically determine the extent of neurological damage following an ischaemic insult. These reports spurred a new interest in brain temperature among clinicians--neurologists and neurosurgeons. The information about this subject is very sparse and the mechanisms of cerebral metabolic heat dissipation are largely obscure. The author recapitulates the current knowledge of the problem and discusses the hypotheses relevant to human cerebral thermoregulation during normothermia and hyperthermia. Clinical relevance of these problems is also discussed. PMID- 7991061 TI - [Evolution of the growth of multiple intracranial tumors in a case of type 2 neurofibromatosis]. AB - A sporadic case of neurofibromatosis type 2 in a 23-year old woman is described with clinical and neuroimaging (CT or MRI) 4 years follow-up. Together with bilateral acoustic tumours multiple intracranial tumours and solitary orbital meningioma were present, the latter being confirmed surgically and histopathologically. Ocular findings of congenital cataract but lack of other external stigmata of neurofibromatosis completed the clinical picture of the disease. Diagnostic criteria of NF2, difficulties in establishing the optimal management options are described and the importance of evaluating of family members is underlined. Neuroimaging pictures showed tumour expansion over 4 years leading to severe disability with total blindness, deafness, paresis and cerebellar syndrome. PMID- 7991063 TI - Current bibliographies of neuropeptides prepared by the University of Sheffield Biomedical Information Service. PMID- 7991062 TI - [Post-traumatic syringomyelia of the spinal cord in nuclear magnetic resonance imaging]. PMID- 7991064 TI - Anxiolytic effect of neuropeptide FMRFamide in rats. AB - Central administration of FMRFamide in rats dose dependently increased the duration of time spent in the open arm of an elevated plus maze and enhanced the number of drink contacts in the thirsty rat conflict test. Similarly in the social interaction test, animals pretreated with FMRFamide spent sufficient time in active social interaction as compared to controls. Neuropeptide FMRFamide antagonized the anxiogenic effect of yohimbine and enhanced the antianxiety effect of diazepam in rats. The results indicate anxiolytic action of FMRFamide and the mechanism of such an action may involve serotonergic transmission. PMID- 7991065 TI - Rapid cleavage of the endogenous PC3 prosegment and slow conversion to 74 kDa and 66 kDa proteins in AtT-20 cells. AB - AtT-20 cells synthesize 87 kDa and 66 kDa forms of the prohormone convertase PC3 (also known as PC1). In the present work, using biosynthetic labeling experiments (performed both at 20 degrees C and at 37 degrees C), followed by immunoprecipitation with aminoterminally and carboxyterminally-directed antisera, we have found that the first PC3 translational product was a 94 kDa protein that was then converted to an 84 kDa form. This processing was extremely rapid, occurring with a half-life of less than 2 min at 20 degrees C. The 84 kDa form was endoglycosidase H-sensitive, indicating a lack of acquisition of sugar transferred in the medial golgi. Dithiothreitol, a reducing agent that prevents the disulfide bond formation of newly synthesized proteins in the endoplasmic reticulum (ER), inhibited the processing of the 94 kDa to the 84 kDa form. However, brefeldin A (BFA), an inhibitor of ER/golgi transport, and monensin, an inhibitor of the medial/trans-golgi transport, did not affect the cleavage of the 94 kDa to the 84 kDa protein. The 84 kDa protein was converted to an endoglycosidase H-resistant form of 87 kDa that was sequentially processed to 74 kDa and 66 kDa proteins. The 87 kDa protein was immunoprecipitated by the PC3 aminoterminally and carboxyterminally-directed antisera, while the 74 kDa and 66 kDa protein were only detected with the aminoterminally-directed antibody. Radiosequencing of the 87 kDa and 66 kDa proteins indicated that the biosynthesis of the 87 kDa proteins involves the removal of the 83 amino acid prosegment, and that the processing of the 87 kDa to 66 kDa form occurred by cleavage at the carboxyterminal portion. BFA and monensin effectively interrupted the processing of the 84-87 kDa protein to the 74 and 66 kDa species. In addition, while the 84 87 kDa protein produced in monensin-treated cells was still sensitive to endoglycosidase H, the 66 kDa protein was resistant to this enzyme. These results indicate that the post-translational processing of PC3 occurs in three steps: (1) rapid conversion, probably in the ER, of the 94 kDa precursor to the 84 kDa protein by removal of the aminoterminus prosegment; (2) cleavage of the 87 kDa protein to an intermediate product of 74 kDa; and (3) production of the 66 kDa protein. The second and third steps occur in late cellular compartments such as the trans-golgi network or secretory granules and involve sequential cleavages at the carboxyterminus.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 7991066 TI - Opioids influence neurohypophysial but not central oxytocin release following direct hyperosmotic stimulation of the supraoptic nucleus in urethane anaesthetised rats. AB - Microdialysis was used to apply an osmotic stimulus (0.5 M NaCl-aCSF) into both supraoptic nuclei (SON) to investigate the role of endogenous opioid peptides in the control of both central and peripheral oxytocin release in response to this stimulus. There were no differences in central peptide release during direct hyperosmotic stimulation between groups of rats given either vehicle, morphine (5 mg/kg) or naloxone (5 mg/kg) intravenously. Naloxone potentiated oxytocin release into blood; this suggests that endogenous opioid peptides at the level of the neurohypophysis, but not in the SON are important modulators of oxytocin release to this stimulus. However morphine blocked oxytocin release into blood indicative of a central inhibitory action on the firing rate of oxytocin neurones, contrasted with insensitivity to morphine of oxytocin secretion from the dendrites stimulated directly by hyperosmolarity. PMID- 7991067 TI - Effect of sulpiride or paroxetine on cerebrospinal fluid neuropeptide concentrations in patients with chronic tension-type headache. AB - In lumbar cerebrospinal fluid (CSF) obtained from patients with chronic tension type headache (CTH), the concentrations of beta-endorphin, met-enkephalin, dynorphin, cholecystokinin (CCK), calcitonin gene-related peptide (CGRP), and somatostatin were measured before and after 8 weeks of treatment with sulpiride or paroxetine. We previously reported higher than normal met-enkephalin concentrations in CTH. The present study reveals normal basal concentrations of CCK, CGRP and somatostatin and slightly decreased dynorphin in the same patients. Treatment with sulpiride or paroxetine did not change the concentration of any of the neuropeptides measured. These data suggest central changes in opioid systems but not in other peptide systems (CCK, CGRP, somatostatin) involved in nociceptive processing at the level of the spinal cord dorsal horn/nucleus caudalis of the trigeminal nerve in CTH. Such central changes might be pathophysiologically important or merely secondary to other more important occurrences. The lack of changes in neuropeptide concentrations during drug treatment makes planning of studies involving CSF analysis easier, but also limits the probability of obtaining information on specific neuropeptide systems through CSF analysis. PMID- 7991068 TI - Anomalous growth hormone response to vasoactive intestinal peptide and peptide histidine methionine in patients with prolactinoma or hypothalamic hyperprolactinemia. AB - We examined a possible GH-releasing activity of vasoactive intestinal peptide (VIP) and its homologous peptide, peptide histidine methionine (PHM), in 22 patients with hyperprolactinemia (HPRL) who comprised 19 cases of prolactinoma (PRLoma) and 3 cases of hypothalamic HPRL. Each patient underwent iv bolus injections of VIP (100 micrograms) and PHM (100 micrograms) on separate days, and plasma levels of GH and PRL were measured. The plasma GH response to VIP and PHM were considered positive (a paradoxical increase) when an increase over baseline of at least 50% occurred. In agreement with previous reports, the PRL-releasing activity of VIP and PHM in our patients with HPRL were subnormal. Thirteen (59%) patients showed a paradoxical rise in GH after VIP, and 4 (18%) patients did so after PHM. It is to be noted that all the 3 patients with hypothalamic HPRL responded to VIP with a significant rise in GH. 3 of the 4 PHM-responders were also responsive to VIP, which suggests that PHM may have activated VIP receptors in the pituitary of the PHM-responders as a partial agonist of the VIP receptor. The responders and nonresponders to VIP or PHM, respectively, had similar results with respect to the mean age, and the mean basal PRL and GH levels in the plasma. Since these paradoxical GH responses were observed in not only the patients with PRLoma but also those with hypothalamic HPRL, it may be that these anomalous GH responses in HPRL were due to the HPRL itself rather than due to the neoplastic lactotrophs.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7991069 TI - The effects of protection by D-Pen2-D-Pen5-enkephalin or D-Ala2-NMePhe4-Gly-ol enkephalin against beta-chlornaltrexamine in the spinal cord on the antinociception induced by beta-endorphin administered intracerebroventricularly in the mouse. AB - Chlornaltrexamine (beta-CNA, 0.5 micrograms) alone or beta-CNA plus either mu agonist, D-Ala2-NMePhe4-Gly-ol-enkephalin (DAMGO, 500 ng) or delta-agonist, D Pen2-D-Pen5-enkephalin (DPDPE, 10 micrograms) was injected intrathecally (i.t.) to protect mu- or delta-opioid receptors, respectively, for 24 h in male ICR mice. The antinociception was assessed by the tail-flick and hot-plate test. DPDPE or DAMGO injected i.t. increased inhibition of the tail-flick and hot-plate response in a dose-dependent manner. The dose-response curve for tail-flick and hot-plate response induced by DPDPE or DAMGO in i.t. saline-treated group significantly shifted to the right in i.t. beta-CNA alone treated group but returned to the control level in the group treated with i.t. beta-CNA coadministered with DPDPE or DAMGO, respectively. The effects of protection of mu and delta-opioid receptor in the spinal cord on inhibition of the tail-flick and hot-plate response induced by beta-endorphin and morphine administered intracerebroventricularly (i.c.v.) were then studied. Intrathecal pretreatment with beta-CNA or beta-CNA coadministered with DAMGO attenuated inhibition of the tail-flick response induced by beta-endorphin administered i.c.v. However, i.t. treatment with beta-CNA coadministered with DPDPE did not affect inhibition of the tail-flick response induced by beta-endorphin administered i.c.v. Intrathecal pretreatment with beta-CNA or beta-CNA coadministered with either DPDPE or DAMGO did not alter inhibition of the hot-plate response induced by beta-endorphin administered i.c.v.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7991070 TI - Lack of involvement of the cholinergic mechanism in vasoactive intestinal peptide and peptide-histidine methionine-induced growth hormone (GH) responses in acromegaly: comparison with the GH responses to thyrotropin-releasing hormone and GH-releasing hormone. AB - We examined whether the cholinergic mechanism is involved in the paradoxical GH responses to vasoactive intestinal peptide (VIP) and peptide histidine methionine (PHM) in acromegaly. 28 patients with active acromegaly underwent i.v. bolus injections of thyrotropin-releasing hormone (TRH, 500 micrograms), GH-releasing hormone (GHRH, 100 micrograms), VIP (100 micrograms), and PHM (100 micrograms) with or without a prior atropine treatment (1 mg, i.m., 30 min before). Blood samples were collected before and at intervals up to 120 min after the injection, and plasma GH levels were measured. In response to TRH, GHRH, VIP and PHM, 23 (82%), 24 (86%), 13 (46%) and 7 (25%) patients, respectively, responded with a significant GH increase (> 50% and 6 micrograms/l above the basal level). The effect of atropine pretreatment was examined in only these responders to the respective peptides. When the GH responses were estimated by the area under the response curve, the atropine pretreatment was able to significantly suppress the GH response to GHRH, but not to TRH, VIP, or PHM. Although the lack of cholinergic involvement in the TRH-induced GH release in acromegaly is confirmatory to previous reports, the same results with the VIP- and PHM-induced GH release are novel. The present study may suggest that in acromegaly the physiological GH response is mediated by the cholinergic mechanism, but the paradoxical ones are not. PMID- 7991071 TI - Proliferogenic effect of neurotensin (NT) and neuromedin-N (NMN) on the rat adrenal cortex: evidence that angiotensin-II mediates the effect of NMN, but not of NT. AB - NT and NMN, two biologically active peptides acting via the same specific receptor, are both able to stimulate in vivo the proliferative activity of rat adrenocortical cells. The present study aimed to investigate whether the mechanism underlying this effect of NT and NMN may involve an enhanced production of angiotensin-II (ANG-II), a potent adrenocortical proliferogenic factor. Metaphases per adrenal section were counted 120 min after vincristine injection. A bolus administration of ANG-II resulted in a marked increase in the number of metaphase-arrested cells 12, 24 and 48 h after the beginning of the experiment; the concomitant administration of saralasin (SAR), a competitive antagonist of ANG-II, completely blocked the proliferogenic effect of ANG-II. NT-evoked rise in the number of metaphases occurred 48 h after administration and was not influenced by the simultaneous SAR injection. On the contrary, NMN injection induced a burst of adrenocortical cell proliferation within 12 h, and this effect was prevented by SAR. These data suggest that ANG-II mediates the proliferogenic effect of NMN, but not that of NT. PMID- 7991072 TI - The Yin and the Yang of visuo-spatial neglect: a case study. AB - We report a patient (R.B.) who has shown gross left visuo-spatial neglect over the 3 years since he sustained a right parietal infarct. Although his neglect is severe on such tasks as line bisection, cancellation, and drawing, there are some domains of preserved perceptual performance: he can perceive subjective contours, he can use lateral symmetry as a cue to figure-ground segregation, and he benefits from some forms of global cueing. In a series of five experiments, we show that R.B. has a selective inability to analyse and copy accurately the left contours of geometric nonsense-figures. These results hold even when there is a single vertical contour (to be copied) that divides a rectangle or a circle into two sub-figures; this physically-identical boundary is copied more accurately when it is cued as the right edge of the left sub-figure than when it is cued as the left edge of the right sub-figure. These effects are not influenced by a manipulation in which R.B. is required to trace the outline of the relevant sub figure with his finger immediately prior to drawing his copy. The results are interpreted in terms of classical Gestalt theories of figure-ground assignment. Pre-attentive (global) figure-ground parsing is basically intact; but when focal attention is demanded, only the right side of an object is coded as figure. PMID- 7991073 TI - Left visuo-spatial neglect can be worse in far than in near space. AB - We tested five patients with marked left-sided visuo-spatial neglect and two control subjects on a test of line bisection. A series of horizontal lines was presented to each subject, who had to indicate the centre with a projection light pen. All five patients misplaced the centre to the right, in accordance with their left-sided neglect. However, in all five the angular displacement was greater for lines well beyond reach, than for lines of identical angular size within reaching distance. This result, precisely because it is opposite to that of a previous report, supports the conclusion that there are separate dissociated neural systems concerned with the perception of, and response to, stimuli in near and far space. PMID- 7991074 TI - Gender differences in laterality patterns for speaking and singing. AB - This study examined behaviors reflecting cerebral organization of speaking and singing in normal college students. The investigation focused on whether differences existed in the laterality patterns of two singing tasks and one speaking task in males and females. Performance was measured on a verbal/manual time-sharing paradigm, coupling finger tapping with three vocal tasks (speaking, singing a rote song, singing up and down a diatonic five note scale). Females exhibited less variation than males in mean tapping rates and laterality scores across all three vocal tasks, thus indicating that gender most likely influences lateralization of vocal tasks. Bilateral integration was indicated for both males and females during singing up/down the aforementioned scale. These findings suggest differential involvement of both hemispheres in processing musical functions. PMID- 7991075 TI - Orienting of attention in deafferented patients. AB - Visual attentional processes were compared in two deafferented patients and 11 normal subjects. Two consecutive stimuli were presented in rapid succession in one of two locations. A peripheral cue first oriented attention to one location where a response was requested. After 100 msec, a second response was required at either the same or opposite location (valid vs invalid cue). Four probabilities of valid cue occurrence were presented: 100, 80, 50 and 20%. Results showed (1) faster reaction times for the second response on cued than on uncued signals; (2) greater attentional effects with increased cue probability; (3) smaller attentional effects in patients. These findings suggest that the patients adopted a cost-minimizing strategy. PMID- 7991076 TI - Visual repetition priming for words relies on access to the visual input lexicon: evidence from a dyslexic patient. AB - In this study we tested the hypothesis that visual repetition priming for words depends upon the accessibility of lexical units in the visual input lexicon. For this purpose, we investigated a dyslexic patient, A.M., whose neuropsychological performances suggested an impaired access to the lexical route of reading. According to the predictions, Experiments 1 and 2 demonstrated deficient priming in tests involving the visual presentation of words (Word Identification and Stem Completion). In Experiment 3, we demonstrated that A.M.'s deficient priming was specific for visually presented words, in that the auditory presentation elicited a normal priming effect (auditory Stem Completion). These data are discussed in the light of a theoretical framework suggesting a fractionation of the modalities by which repetition priming can be elicited, each mediated by a particular memory subsystem. PMID- 7991077 TI - Pure anomia with spared action naming due to a left temporal lesion. AB - We report the case of a patient who, after surgical ablation of an angioma in the depth of the left temporal lobe, developed a highly selective impairment of naming. A detailed investigation allowed to exclude a disorder of visual recognition or of semantic memory, and indicated the output lexicon as the most probable site of impairment. Grammatical class effects, with superior action naming, and a high consistency within and across output modalities further characterized the patient's performance. Together with some other recently reported cases, this patient suggests a correlation between temporal lobe lesions outside Wernicke's area and output lexicon disorders. A relatively spared action naming seems to be a characteristic feature of this pattern of impairment. PMID- 7991078 TI - Impairments of movement execution in unilateral neglect: a kinematic analysis of directional bradykinesia. AB - A kinematic analysis was performed on goal-directed movements made by 14 patients with right hemisphere damage and left unilateral neglect (seven mild, seven severe), and 14 healthy controls. Leftward and rightward pen strokes of varying extents were made to targets of varying size on a centrally located digitising tablet. While mild unilateral neglect patients performed like controls, patients with severe unilateral neglect were slower to initiate leftward than rightward strokes and were slow and inefficient in movement execution. Leftward strokes made by severe unilateral neglect patients were characterised by prolonged movement time, lower peak velocity and departed from optimal bell-shaped velocity profiles. Their leftward strokes also showed prolonged accelerative phases, implying difficulties in force production, while the high proportion of their total movement time spent in decelerating with rightward strokes suggested an abnormal emphasis on terminal visual guidance. Leftward strokes made by these patients also contained more submovements than rightward strokes, suggesting poor force control. An impaired internal representation of the location of left-sided targets and desired movement trajectories in severe unilateral neglect causes breakdown in the temporal control of goal-directed movements. PMID- 7991079 TI - Long lasting indirect memory performance for abstract shapes in amnesics and matched controls. AB - The speed with which subjects copied complex geometrical shapes was used as an indirect memory measure in a group of 12 organic amnesics of several aetiologies and their matched controls, tested at two delays. Both subject groups were found to copy previous seen shapes faster than new foil shapes, and the magnitude of the speed up effect did not differ significantly between amnesics and matched controls when tested at two delays of 10 min and 24 hr, respectively. The size of the indirect memory effect did not decline across the delay in either group. In contrast to indirect memory performance, measured by two-choice recognition of the shapes, was impaired in the amnesic group and there was some suggestion that recognition performance declined across the delay in both subject groups. PMID- 7991080 TI - Perceptual flexibility after frontal or temporal lobectomy. AB - Using stimuli with ambiguous figure-ground relationships, Ricci and Blundo (1990, Neuropsychologia 28, 1163-1173) demonstrated that patients with frontal-lobe lesions are impaired at shifting perspective. No significant difference between right frontal and left frontal groups was found. To investigate this phenomenon further and to look for a possible lateralization-of-lesion effect, 31 patients who had undergone focal cortical excision for the relief of intractable epilepsy and 10 normal control subjects were tested on an expanded version of the original task. It was found that no subjects had any difficulty recognizing at least one aspect in each of the figures and that only patients with right frontal lesions were significantly impaired in recognizing a second. These results indicate that the right frontal region has a particularly important role in the ability to shift visual perspective. PMID- 7991081 TI - Prediction of delayed neurological deficit after subarachnoid haemorrhage: a CT blood load and Doppler velocity approach. AB - The predictive value of cranial computed tomography (CT) blood load and serial transcranial Doppler sonography for the development of delayed ischaemic neurological deficit was assessed in 121 patients following subarachnoid haemorrhage. Of the 121 patients, 81 (67%) had thick layers of blood or haematoma, including intraventricular bleeding. The proportion of patients who developed delayed deficit was higher with increasing amounts of subarachnoid blood on the admission CT (51% of 53 cases in Fisher grade 3; 35% of 33 cases in grade 2; 28% of 7 cases in grade 1, P < 0.01). Doppler velocities obtained from readings at least every 2 days following admission were higher in patients with delayed neurological deficit (peak velocity for grade 3 patients 176 +/- 6 cm/s (mean +/- SE), versus grade 2: 164 +/- 7 cm/s; grade 4 149 +/- 9, both P = 0.04, Mann-Whitney). Peak velocity and maximal 24-h rise tended to be higher within different CT grades in patients with a deficit than in those without; this difference was significant for grade 3 patients (P < 0.01). We conclude that a combined approach with CT and Doppler sonography provides greater predictive value for the development of delayed ischaemic neurological deficit than either test considered independently. The value of Doppler sonography may be greatest for patients with Fisher grade 3 blood, in whom the risk of delayed ischaemia is greatest. PMID- 7991082 TI - The value of MRI in angiogram-negative intracranial haemorrhage. AB - In one year, cerebral angiograms were performed for intracranial haemorrhage (ICH) on 334 patients. No cause for haemorrhage could be identified in 41 (12%), 30 of whom had predominantly subarachnoid (SAH) and 11 predominantly parenchymal haemorrhage (PH). These patients were prospectively examined by cranial MRI 1-6 weeks after the ictus. The MRI studies were positive in 7 patients (17%). In the 30 patients examined after SAH, 2 studies were positive, showing an aneurysm in one case and a brain stem lesion of uncertain aetiology in the other. In those examined after PH, cavernous angiomas were shown in 2, a tumour in 1 and a vascular malformation in another; useful diagnostic information was thus obtained in 36% of this group. PMID- 7991083 TI - Imaging in acute basilar artery thrombosis. AB - The aim of this study was to review the imaging features in acute (< 24 h) basilar artery thrombosis. CT and MR studies in 11 patients with clinical diagnosis of acute basilar artery thrombosis were retrospectively reviewed. MR angiography was obtained in 4 patients. Correlation with clinical symptoms was performed. Multiple cranial nerve palsies and hemiparesis were the most common clinical symptoms at presentation. CT revealed hyperdense basilar arteries (n = 7) and hypodensities in the posterior circulation territory (n = 8). In one instance, the infarction was hemorrhagic. MR imaging showed absence of flow void within the basilar in 6 patients and MRA (using both PC and TOF techniques) confirmed absence of blood flow in 4 basilar arteries. One week after presentation, 5 patients died. Autopsy was obtained in 1 case and confirmed the diagnosis of basilar artery thrombosis. Basilar artery thrombosis has fairly typical imaging features by both CT and MR. MRA may be used to confirm the diagnosis. Prompt recognition may lead to early thrombolytic treatment and may improve survival. PMID- 7991085 TI - Moyamoya disease: diagnosis with three-dimensional CT angiography. AB - Our purpose was to assess the value of three-dimensional (3D) CT angiography in the diagnosis of moyamoya disease. We studied seven patients with moyamoya disease proved by conventional angiography. Three-dimensional (3D) CT angiography was performed using rapid sequence or helical (spiral) scanning in conjunction with a bolus injection of intravenous contrast medium. All seven patients could be diagnosed as having moyamoya disease on the basis of the following 3D CT angiographic findings: poor visualisation of the main trunks and/or major branches of anterior and middle cerebral arteries (7 patients); dilated leptomeningeal anastomotic channels from the posterior cerebral arteries (4); and demonstration of "moyamoya vessels" in the basal ganglia (2). Although conventional angiography remains the principal imaging technique for demonstrating anatomical changes in detail, less invasive 3D CT angiography provides a solid means of diagnosing moyamoya disease when it is suspected on CT, MRI, or clinical grounds. PMID- 7991084 TI - Striatocapsular infarction: MRI and MR angiography. AB - We present a case of left striatocapsular infarction manifest clinically as a transient right hemiparesis. MRI showed a left striatocapsular infarct. Striatocapsular infarction, unlike lacunar infarction, is often associated with occlusive disease of the carotid artery. In order to screen the carotid vessels, cervical MR angiography (MRA) was performed during the same examination, demonstrating a left internal carotid artery occlusion, confirmed by contrast arteriography. MRA, a noninvasive modality, can be a useful adjunct to MRI, when diagnostic information concerning the cervical carotid artery is needed. PMID- 7991086 TI - Three-dimensional spiral CT for neurosurgical planning. AB - We carried out 22 examinations to determine the value of three-dimensional (3D) volumetric CT (spiral CT) for planning neurosurgical procedures. All examinations were carried out on a of the first generation spiral CT. A tube model was used to investigate the influence of different parameter settings. Bolus injection of nonionic contrast medium was used when vessels or strongly enhancing tumours were to be delineated. 3D reconstructions were carried out using the integrated 3D software of the scanner. We found a table feed of 3 mm/s with a slice thickness of 2 mm and an increment of 1 mm to be suitable for most purposes. For larger regions of interest a table feed of 5 mm was the maximum which could be used without blurring of the 3D images. Particular advantages of 3D reconstructed spiral scanning were seen in the planning of approaches to the lower clivus, acquired or congenital bony abnormalities and when the relationship between vessels, tumour and bone was important. PMID- 7991087 TI - Neuroradiological features of intracranial and intraorbital meningeal haemangiopericytomas. AB - The neuroradiological features of six intracranial and one intraorbital haemangiopericytomas (HP) are reviewed. CT was performed before and after IV contrast medium in 5 patients. In 2 patients MRI was performed before and after contrast medium; in another, only unenhanced images were obtained. Five patients were studied by selective external and internal carotid artery angiography. Women constituted 5 of the 7 patients, and the mean age was 50.5 years, thus the sex and age distribution did not differ from that of typical meningiomas. Contrary to previous reports, calcification was present in two of the intracranial HP, and bone erosion was clearly seen in one intracranial HP and the orbital lesion. On MRI the tumours showed no differences from angioblastic meningiomas. All 6 intracranial HP were aggressive: all recurred following treatment and extracerebral metastasis occurred in one case. PMID- 7991088 TI - MRI of pleomorphic xanthoastrocytoma: case report. AB - MRI showed a cortically-based partially cystic and markedly enhancing mass in the uncus of the right temporal lobe in a patient with long standing refractory partial complex seizures. Histopathological examination revealed a pleomorphic xanthoastrocytoma, a rare, usually benign tumour thought to originate from subpial astrocytes. PMID- 7991089 TI - Magnetic resonance imaging of the normal and chronically injured adult rat spinal cord in vivo. AB - We assessed the capacity of MRI to show and characterise the spinal cord (SC) in vivo in normal and chronically injured adult rats. In the chronically injured animals the SC was studied by MRI and histological examination. MRI was performed at 1.5 T, using gradient-echo and spin-echo (SE) sequences, the latter with and without gadolinium-DTPA (Gd-DTPA). Several positions were tried for good alignment and to diminish interference by respiratory movements. Images of the SC were obtained in sagittal, coronal, and axial planes. Normal SC was observed as a continuous intensity in both sequences, although contrast resolution was better using SE; it was not possible to differentiate the grey and white matter. Low signal was seen in the damaged area in chronically injured rats, which corresponded to cysts, trabeculae, mononuclear infiltrate, and fibroglial wall on histological examination. Gd-DTPA failed to enhance the SC in normal or chronically injured rats. It did, however, cause enhancement of the lesion after acute SC injury. PMID- 7991090 TI - Posterior lumbar apophyseal ring fractures: a report of 20 cases. AB - Posterior apophyseal ring fracture (PARF) of the lumbar spine is an uncommon injury thought usually to occur in adolescence. We analysed CT findings in 20 cases (19 patients), whose age ranged from 16 to 45 years (average 30 years). The PARF could be divided into two distinct groups on the basis of the shape and location of the fracture and the defect of the vertebral rim. In group 1 (2 cases), PARF involved the central aspect of the inferior vertebral rim and bone fragments were large and broad-based. In group 2, PARF were located at the posterolateral margin of the superior vertebral rim and bone fragments were small and focal. The great majority of previously reported cases belonged to our group 1. A pathogenesis for each group is suggested. PMID- 7991092 TI - Cystic lumbar meningioma presenting as a ring enhancing lesion on MRI. PMID- 7991091 TI - Spinal epidural haematoma: report of 11 cases and review of the literature. AB - Spinal epidural haematomas (SEH) are rare; most are caused by trauma, anticoagulant therapy, vascular anomalies, hypertension, blood dyscrasias, epidural anaesthesia or, rarely, spinal surgery. We report 11 cases and review the literature (16 cases). The clinical picture is that of acute spinal cord compression. MRI characteristics are quite specific. On sagittal sections, the SEH appears as a biconvex mass, dorsal to the thecal sac, clearly outlined and with tapering superior and inferior margins. The dura mater is seen as curvilinear low signal separating the haematoma from the cord. Within 24 h of onset, the haematoma is isointense with the cord on T1-weighted images and heterogeneous on T2-weighted images. Later, it gives high signal on both T1- and T2-weighted images. Differential diagnosis must include subdural haematoma, epidural neoplasm and abscess. Complete neurological recovery rapidly follows laminectomy and removal of the clot. In three of our cases, the haematoma resolved spontaneously. MRI is the best examination for diagnostic and follow-up. PMID- 7991093 TI - 3D-FT MRI of the facial nerve. AB - Contrast-enhanced 3D-FT MRI of the intrapetrous facial nerve was obtained in 38 patients with facial nerve disease, using a 1.0 T magnet and fast gradient-echo acquisition sequences. Contiguous millimetric sections were obtained, which could be reformatted in any desired plane. Acutely ill patients, were examined within the first 2 months, included: 24 with Bell's palsy and 6 with other acute disorders (Herpes zoster, trauma, neuroma, meningeal metastasis, middle ear granuloma). Six patients investigated more than a year after the onset of symptoms included 3 with congenital cholesteatoma, 2 with neuromas and one with a chronic Bell's palsy. The lesion was found incidentally in two cases (a suspected neurofibroma and a presumed drop metastasis from an astrocytoma). Patients with tumours had nodular, focally-enhancing lesions, except for the leptomeningeal metastasis in which the enhancement was linear. Linear, diffuse contrast enhancement of the facial nerve was found in trauma, and in the patient with a middle ear granuloma. Of the 24 patients with an acute Bell's palsy 15 exhibited linear contrast enhancement of the facial nerve. Three of these were lost to follow-up, but correlation of clinical outcome and contrast enhancement showed that only 4 of the 11 patients who made a complete recovery and all 10 patients with incomplete recovery demonstrated enhancement. Possible explanations for these findings are suggested by pathological data from the literature. 3D-FT imaging of the facial nerve thus yields direct information about the of the nerve condition and defines the morphological abnormalities. It can also demonstrate contrast enhancement which seems to have some prognostic value in acute idiopathic Bell's palsy. PMID- 7991094 TI - Sinonasal polyposis: investigation by direct coronal CT. AB - To demonstrate the typical clinical and CT features of sinonasal polyposis, we reviewed the clinical records and preoperative direct coronal CT scans of 35 patients with surgically proven disease. Symptoms included progressive nasal stuffiness (100%), rhinorrhea (69%), facial pain (60%), headache (43%) and anosmia (17%). We found associations with rhinitis (46%), asthma (29%) and aspirin sensitivity (9%). Coronal CT features included polypoid masses in the nasal cavity (91%), partial or complete pansinus opacification (90%), enlargement of infundibula (89%), bony attenuation of the ethmoid trabeculae (63%) and nasal septum (37%), opacified ethmoid sinuses with convex lateral walls (51%) and air fluid levels (43%). The latter feature correlated with symptoms and signs of acute sinusitis in only 40% of patients. Recognition of sinonasal polyposis is important to the endoscopic surgeon since it can be the most troubling sinonasal inflammatory disease to manage due to its aggressive nature and tendency to recur despite appropriate treatment. PMID- 7991096 TI - MRI and CT in Krabbe's disease: case report. AB - A case of infantile Krabbe's disease was first recognised as areas of relatively increased density on CT in the thalamus lateral geniculate body and dentate nucleus. These sites were subsequently shown on MRI to have a paramagnetic effect, being characterised by short T2 and T1. Subsequent examinations showed development of atrophy and high signal in white matter. PMID- 7991095 TI - MRI of the brain in muscle-eye-brain (MEB) disease. AB - Muscle-eye-brain (MEB) disease belongs to the spectrum of rare congenital syndromes with migration disorders of the brain and muscular dystrophy, along with the Walker-Warburg syndrome and Fukuyama congenital muscular dystrophy. Their features overlap, and differential diagnosis presents some difficulties. We examined the brain of 10 patients with MEB using high-field MRI and found a uniform pattern consisting of a pachygyria-type cortical migration disorder, septal and corpus callosum defects and severe hypoplasia of the pons in 7 of them. PMID- 7991097 TI - Aplasia cutis congenita of the scalp with large underlying skull defect: a case report. AB - Localised agenesis of the scalp is the most frequent pattern in aplasia cutis congenita (ACC), a congenital absence of the skin and occasionally of deeper layers. Several clinical groups are characterised by the location and pattern of skin defects, associated malformations and the mode of inheritance. Death occurs in 20% of cases, secondary to the associated anomalies, to infections or to haemorrhage from ulceration of the sagittal sinus when there is also a defect of the underlying skull. In this latter case, we close the defect by two rotational scalp flaps (Orticochea technique) at birth. A three-dimensional CT study is useful for showing the extent of the skull defect and the deformity of the craniofacial complex and the changes in the bone after treatment. PMID- 7991098 TI - Percutaneous cervical diskectomy: preliminary experience. AB - We assessed the feasibility of percutaneous treatment of a cervical herniated disc. In the lumbar region, the surgical instrument for percutaneous diskectomy passes only through the paravertebral muscles, while in the cervical region there is considerable risk of nervous, parenchymal and vascular lesions. Moreover, open surgery for cervical herniated nucleus pulposus is a well-established, low-risk procedure, with little risk of epidural fibrosis, the main complication of lumbar open surgery; a percutaneous procedure should therefore have a low morbidity rate. A safe percutaneous approach to cervical discs could be useful for biopsy and for treatment of high-risk patients for general anaesthesia. We treated 15 patients with cervical herniated nucleus pulposus; all gave informed consent and refused or were not eligible for open surgery. We used the Nucleotome described for treatment of lumbar herniated discs; except for the first three cases, we used colour Doppler sonography to detect hazardous structures in the path of the probe. We had one complication, a cervical haematoma due to damage to the inferior thyroid artery, prior to the use of ultrasound. PMID- 7991099 TI - Embolisation of orbital varix. AB - A 34-year-old man with intermittent exophthalmos, found to have a large varix in the right orbit, was treated by endovascular surgery. Percutaneous transfemoral venous catheterisation and embolisation of the orbital varix was performed on two occasions. A Tracker 18 microcatheter was introduced through the right inferior petrosal sinus, cavernous sinus, superior ophthalmic vein and then into the varix, following a guidewire. Superselective venography of the right ophthalmic vein showed the varix. A total of 204 platinum microcoils was used to pack the varix. At the time of discharge, the exophthalmos had largely resolved. As this technique is much less invasive than surgical resection, we recommend an attempt at endovascular embolisation of orbital varices prior to surgical removal. PMID- 7991100 TI - Epidural arteriovenous fistula with perimedullary venous drainage: case report. PMID- 7991101 TI - Lucien Appel prize for neuroradiology 1994. PMID- 7991102 TI - Neurosyphilis. PMID- 7991103 TI - Medical medullary syndrome and meningovascular syphilis: a case report in an HIV infected man and a review of the literature. PMID- 7991104 TI - Paraneoplastic autoantibodies: the case for a descriptive generic nomenclature. PMID- 7991105 TI - Neurologic paraneoplastic antibodies (anti-Yo; anti-Hu; anti-Ri): the case for a nomenclature based on antibody and antigen specificity. PMID- 7991106 TI - Clozapine-related seizures: experience with 5,629 patients. AB - We reviewed the incidence, clinical features, and management of all clozapine related seizures in 5,629 patients monitored by the Clozaril Patient Management System, during the first 6 months after marketing. Seventy-one patients had generalized tonic-clonic seizures yielding a frequency of 1.3%. One patient had myoclonic seizures prior to generalization. Seizures tended to occur at low doses (< 300 mg/d) during the titration phase, and at high doses (> or = 600 mg/d) during the maintenance phase. Patients with a history of seizures or epilepsy were more likely to have seizures soon after initiation of therapy, on low doses. Twenty-nine of 37 patients (78%) who had seizures and were rechallenged with clozapine were able to continue the medication with dose reduction and more gradual dose titration, or with the addition of an antiepileptic medication. PMID- 7991107 TI - Hereditary neuralgic amyotrophy and hereditary neuropathy with liability to pressure palsies: two distinct clinical, electrophysiologic, and genetic entities. AB - Hereditary neuralgic amyotrophy (HNA) is an autosomal disease characterized by painful episodes of brachial palsy. The presence of tomacula in some patients suggested that HNA might be genetically related to hereditary neuropathy with liability to pressure palsies (HNPP), caused by point mutations in the PMP22 gene or deletion of the region containing this gene. In a clinical, electrophysiologic, and molecular study of two families with HNA, we show that the PMP22 gene is not deleted, duplicated, or mutated in HNA and that the disease is not linked to any other gene in the HNPP deleted region. We conclude that HNA and HNPP are distinct genetic entities. PMID- 7991109 TI - Indolent anti-Hu-associated paraneoplastic sensory neuropathy. AB - Paraneoplastic sensory neuropathy (PSN) usually runs a subacute progressive course, leaving the patient with severe sensory dysfunction in weeks to months. We describe five patients with PSN, high titers of anti-Hu antibodies (type 1 antineuronal nuclear autoantibodies), and an indolent clinical course. The patients had a median age of 55 years (range, 41 to 72). Four had small-cell (3) or undifferentiated large-cell (1) lung cancer. Patients presented with mild, asymmetric sensory symptoms; in two, the neuropathy was predominant in the arms. Two patients also had a visceral neuropathy causing gastrointestinal dysfunction. The PSN was stable or progressed very slowly without treatment for a median of 18 months (range, 5 to 32) and remained so after treatment with immunoglobulins (1 patient), chemotherapy (3), or both therapies (1). All patients were ambulatory, leading an independent life up until the time of the last visit or until death from the tumor (2 patients). The median follow-up was 36 months (range, 22 to 52). A paraneoplastic origin should be considered in patients with mild, very slowly progressive sensory neuropathies. PMID- 7991108 TI - Hereditary neuralgic amyotrophy and hereditary neuropathy with liability to pressure palsies: two distinct genetic disorders. AB - Hereditary neuralgic amyotrophy with predilection for the brachial plexus (HNA) and hereditary neuropathy with liability to pressure palsies (HNPP) are autosomal dominant disorders associated with episodic, recurrent brachial neuropathies. HNPP is associated with a deletion or abnormal structure of the PMP22 gene on chromosome 17p11.2-12. The genetic locus for HNA is unknown. To address the possibility that HNPP and HNA might be identical disorders or allelic variations at the same locus, we investigated three HNA pedigrees with markers from the HNPP region. We did not find the 17p11.2-12 deletion associated with HNPP, nor an abnormality in PMP22 structure with HNA. This analysis provides genetic evidence, in addition to that suggested by the clinical, electrophysiologic, and pathologic differences, that HNA and HNPP are distinct disorders. PMID- 7991110 TI - Laryngeal botulinum toxin injections for disabling stuttering in adults. AB - Stuttering is an action-induced speech disorder with involuntary, audible, or silent repetitions or prolongations in the utterance of short speech elements (sounds, syllables) and words. Symptomatic treatment programs frequently have initial success; persistent benefit is variable and many patients remain disabled. Stuttering has many characteristics similar to spasmodic dysphonia (laryngeal dystonia), often including the presence of adductor laryngeal spasms that obstruct airflow (glottal block). We hypothesized that relief of the spasmodic dysphonic glottal blocks in stutterers would modify the stuttering phenomenon and increase fluency. We therefore studied the effects of bilateral vocal fold injections of botulinum toxin type A (BTX) on dysfluency and speech characteristics in stuttering. We treated 14 adult patients (12 men, 2 women) with persistent stuttering and glottal block who previously failed standard speech therapy with 1.25 U BTX into each thyroarytenoid (vocalis) muscle. Fluency evaluations included the Stuttering Severity Instrument, the Perceptions of Stuttering Inventory, and a global rating scale (percent of normal function). Patients were evaluated at baseline and at 2-, 6-, and 12-week follow-up visits. Improvement in fluency documented by each rating instrument occurred at 2 and 6 weeks, with functional relapse by 12 weeks in most patients. We conclude that therapeutic laryngeal injections of botulinum toxin are useful in the management of stuttering with glottal block and result in a moderate improvement in fluency. When an adult patient with developmental stuttering with glottal blocks has failed speech interventional therapy and presents for treatment, a trial of BTX can be considered early.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7991111 TI - A method to improve interrater reliability of visual inspection of brain MRI scans in dementia. AB - MR scanning is used in the clinical evaluation of patients with dementia but lacks a reliable method of visual inspection. Two neurologists conducted multiple pilot trials of alternate methods for visual inspection of MRIs, including methods that produced at least 75% interrater agreement in repeat trials, and selected a final method for rating ventricular:brain ratio (VBR), cortical atrophy, and white matter changes. Two other neurologists, new to the method, tested interrater reliability for each component of the method after a brief training session. The correlation of VBR measurement was 0.884 (p = 0.0001). The weighted kappa scores were 0.68 for overall frontal lobe atrophy, 0.38 for right temporal lobe atrophy, 0.20 for left temporal lobe atrophy, and 0.54 for parietal lobe atrophy. The weighted kappa scores were 0.77 for overall periventricular white matter hyperintensities and 0.72 for centrum semiovale hyperintensities. The proposed method may provide a rapid and reliable way to assess VBR, frontal lobe atrophy, parietal lobe atrophy, and white matter changes on brain MRIs in the evaluation of dementia, but it was less reliable for the assessment of temporal lobe atrophy. PMID- 7991112 TI - Parietal lobe epilepsy: clinical features and seizure localization by ictal SPECT. AB - We studied clinical and ictal single-photon emission computed tomography (SPECT) features in 14 patients with parietal lobe epilepsy, nine of whom had structural parietal lobe lesions. Thirteen patients had simple partial seizures of somatosensory (eight), psychic (four), and motor (nine) types. Complex partial seizures (CPS) occurred in seven patients; six were psychoparetic (prominent staring, relative immobility) and one had hyperkinetic activity. Seizures lasted 7 to 110 seconds; 99mTc-HMPAO (hexamethylpropylene amine oxime) was injected ictally, 7 to 89 seconds from seizure onset and 0 to 74 seconds (mean, 21.0 +/- 24.4 seconds) before seizure termination. Ictal SPECT demonstrated focal areas of parietal hyperperfusion in all 14 cases and corresponded with sites of the structural lesions. Parietal hyperperfusion was anterior in eight, posterior in four, and diffuse in two. Quantitative analysis revealed increases in parietal side-to-side perfusion ratios on ictal compared with interictal scans of 11 to 51% (mean, 25.5 +/- 14.4%). Ictal SPECT localization correlated with two main clinical seizure patterns: an anterior syndrome characterized by sensorimotor manifestations and a posterior syndrome characterized by CPS of the psychoparetic type. Ictal SPECT is helpful for localization of parietal seizures. Parietal hyperperfusion is discrete and short-lived, demanding true ictal injections for diagnostic studies. PMID- 7991113 TI - Relationship between antisaccades and the clinical symptoms in Parkinson's disease. AB - We studied voluntary control of saccadic eye movement in 32 parkinsonian patients using the antisaccade task (the subjects were instructed not to look at the target but to look in the opposite direction). Mean latencies and error rates in the antisaccade task were significantly increased in advanced parkinsonian patients. The latencies of the antisaccades correlated with the severity of bradykinesia as well as the results of the Wisconsin Card Sorting Test. Patients taking anticholinergics showed significantly higher error rates. These results suggest that disturbance in the initiation of voluntary saccades in advanced patients may be associated with frontal lobe dysfunction, while anticholinergics may affect the inhibitory control of reflexive saccades. PMID- 7991114 TI - A reduction in serum glucocorticoids provokes experimental allergic encephalomyelitis: implications for treatment of inflammatory brain disease. AB - Glucocorticoid (GCC) therapy usually inhibits inflammatory diseases, but certain regimens can trigger relapses. Clinical use of steroids is not uniform and in some instances may be dangerous. In the present study, GCCs modified the course of experimental allergic encephalomyelitis (EAE) in Lewis rats, a model of inflammatory CNS disease. Continuous treatment with dexamethasone (DEX) completely blocked EAE. RU 486, a GCC antagonist, counteracted the effects of endogenous GCCs and worsened EAE. Sudden withdrawal of DEX also caused severe clinical and histologic exacerbations at a time when paired saline-treated animals had completely recovered. In rats that had complete clinical recovery from EAE, and would not have relapsed without this acute steroid deficit, a short pulse of DEX was followed by severe exacerbations. In contrast, a slow steroid taper prevented exacerbations. Abrupt discontinuation of GCCs provokes inflammatory brain disease. PMID- 7991115 TI - In situ demonstration of the HTLV-I genome in the spinal cord of a patient with HTLV-I-associated myelopathy. AB - Using polymerase chain reaction (PCR) and in situ hybridization, we investigated the HTLV-I genome in the CNS of an HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/TSP) patient with a 20-year disease duration. Neuropathologically, there was severe white matter degeneration throughout the spinal cord, but lymphocytic infiltrates were not evident in any lesion. PCR amplification of the pX region of HTLV-I DNA detected its sequence in the spinal cord and all extra-CNS tissue samples. In situ hybridization using probes complementary to the pX and gag regions detected the HTLV-I genome in the cytoplasm and nucleus of cells in the thoracic cord. The findings indicate a direct involvement of HTLV-I in the neurodegeneration of HAM/TSP. PMID- 7991116 TI - Utility of extrapyramidal signs and psychosis as predictors of cognitive and functional decline, nursing home admission, and death in Alzheimer's disease: prospective analyses from the Predictors Study. AB - OBJECTIVE: To examine whether either extrapyramidal signs or psychotic features are associated with more rapid progression of Alzheimer's disease. BACKGROUND: It has been unclear whether extrapyramidal signs and psychosis are predictors of faster course or are simply late signs. METHODS: Two hundred thirty-six patients with mild Alzheimer's disease were recruited in three cities and followed semiannually. RESULTS: Using Cox proportional hazards models that adjusted for age, sex, disease severity, and estimated duration of illness at study entry, the presence of extrapyramidal signs at entry was associated with higher relative risk (RR) of reaching moderate cognitive (RR = 2.35, 95% CI = 1.12 to 4.92) or functional (RR = 2.31, 95% CI = 1.37 to 3.90) severity, nursing home entry (RR = 2.51, 95% CI = 1.32 to 4.76), or death (RR = 3.04, 95% CI = 1.31 to 7.05). Psychosis predicted only the functional end point (RR = 1.85, 95% CI = 1.18 to 2.90). Using regression models, modified Mini-Mental State scores declined 1.30 points (95% CI = 0.16 to 2.44) per 6-month interval, more among patients with than those without extrapyramidal signs; patients with psychosis declined 1.15 (95% CI = 0.52 to 1.77) more mMMS points per interval. CONCLUSIONS: This study confirms extrapyramidal signs and psychosis as robust predictors of disease end points and rapid progression in Alzheimer's disease. PMID- 7991118 TI - The Clinician Interview-Based Impression (CIBI): a clinician's global change rating scale in Alzheimer's disease. AB - Global assessments are Food and Drug Administration-required primary outcome measures in trials of putative antidementia drugs. Global ratings are intended to provide an index of clinical importance of change that cannot be obtained from quantitative assessment measures such as mental status examinations. We examined the performance of a global assessment of change instrument, the Clinician Interview-Based Impression (CIBI), in the placebo group of a 30-week, randomized, double-blind clinical trial of tacrine in patients with Alzheimer's disease. Initially there were 184 placebo patients, of whom 125 completed the 30-week study. Descriptive statistics, correlations with changes on other assessment instruments, and test-retest reliability were determined for the CIBI. At week 30, clinicians rated more than 40% of patients on the CIBI as unchanged. The CIBI ratings were weakly but significantly correlated, in the expected direction, with change scores on the quantitative cognitive assessments. The CIBI was modestly reliable on test-retest at weeks 22 and 24 but less reliable compared with other quantitative outcome measures. Modifications of the CIBI that might improve its reliability and acceptance include (1) no restrictions on the form of the bedside mental status assessment, (2) inclusion of caregiver input, and (3) better definition of ratings on the global scale. Global instruments, if properly constructed, can provide an index of clinically important change for the assessment of dementia patients. PMID- 7991117 TI - The Neuropsychiatric Inventory: comprehensive assessment of psychopathology in dementia. AB - We developed a new instrument, the Neuropsychiatric Inventory (NPI), to assess 10 behavioral disturbances occurring in dementia patients: delusions, hallucinations, dysphoria, anxiety, agitation/aggression, euphoria, disinhibition, irritability/lability, apathy, and aberrant motor activity. The NPI uses a screening strategy to minimize administration time, examining and scoring only those behavioral domains with positive responses to screening questions. Both the frequency and the severity of each behavior are determined. Information for the NPI is obtained from a caregiver familiar with the patient's behavior. Studies reported here demonstrate the content and concurrent validity as well as between-rater, test-retest, and internal consistency reliability; the instrument is both valid and reliable. The NPI has the advantages of evaluating a wider range of psychopathology than existing instruments, soliciting information that may distinguish among different etiologies of dementia, differentiating between severity and frequency of behavioral changes, and minimizing administration time. PMID- 7991119 TI - Wada memory performance predicts seizure outcome following anterior temporal lobectomy. AB - We examined the ability of Wada memory testing to predict seizure outcome 1 year following anterior temporal lobectomy. Asymmetry scores for Wada memory performance, using amobarbital doses of 125 mg or less, were calculated for 55 patients under the age of 45 years who had no radiologic evidence of structural lesions other than gliosis. Wada memory asymmetries were significantly greater (p < 0.02) in patients who were seizure free compared with those who continued to experience seizures. Furthermore, patients with Wada memory score asymmetries of at least three objects (maximum = 8) were more likely to be seizure free compared with patients with Wada memory asymmetries less than three (p < 0.01). Of the 36 patients who had Wada memory score asymmetries of at least three objects, 32 (89%) were seizure free. In contrast, of the 19 patients whose Wada memory score asymmetries were less than three, only 12 (63%) were seizure free. These data suggest that Wada memory performance is related to seizure outcome following anterior temporal lobectomy. PMID- 7991120 TI - Predictors of outcome after anterior temporal lobectomy: the intracarotid amobarbital test. AB - The intracarotid amobarbital test (IAT) examines hemispheric memory and language. We set out to determine whether memory performance on the IAT correlated with seizure relief after anterior temporal lobectomy in 117 patients with refractory epilepsy. The IAT assessed recognition memory performance for nine items with correction for false-positive recognitions. We then compared performance of one hemisphere with that of the other, defining a correctly lateralized memory deficit as worse performance when using the hemisphere containing the operated temporal lobe than when using the other hemisphere. The analysis included concurrent factors that might also affect outcome, such as age at first risk for epilepsy, presence or absence of tumor, and Full Scale IQ. A discriminant function analysis demonstrated that patients with a correctly lateralized memory deficit on the IAT had an increased probability of being seizure-free following surgery after controlling for other predictors. The performance of the nonoperated temporal lobe related to outcome, although less strongly. The magnitude of the difference in performance between the two hemispheres and the performance of the operated hemisphere did not relate to outcome. Patients who became seizure-free had an earlier age at first risk than did those with persistent seizures, and tumor presence weakly correlated with postoperative outcome. IQ did not correlate with outcome. We conclude that the IAT predicts seizure relief after anterior temporal lobectomy independent of other known risk factors we examined. PMID- 7991121 TI - Predictors of outcome after anterior temporal lobectomy: positron emission tomography. AB - We assessed the relationship between temporal lobe metabolism measured quantitatively and qualitatively with PET using [18F]-fluorodeoxyglucose (FDG) and postoperative seizure frequency after anterior temporal lobectomy. Forty three patients with refractory partial epilepsy had anterior temporal lobectomy and preoperative assessment with PET-FDG. Qualitative PET analysis was performed visually by two blinded observers, and quantitative PET analysis was performed using an anatomic template for six control and six temporal lobe subregions, deriving an asymmetry index for each region. Seizure outcome was assessed 1 year after surgery; patients were classified as being seizure-free or as having persistent seizures. Qualitative data were analyzed using Fisher's exact test and the t test, and quantitative data were analyzed using a repeated-measures ANOVA. Thirty-two patients (74%) were seizure-free at follow-up, and 11 had persistent seizures, although most improved. Twenty-nine of 35 patients (83%) with restricted temporal lobe hypometabolism by visual analysis were seizure-free, compared with three of eight patients (37.5%) with normal scans or multilobar hypometabolism. Quantitative analysis revealed that an asymmetry of mesial temporal lobe glucose consumption (uncal region) correlated with improved surgical outcome (p < 0.02). We developed a logistic regression model to predict individual outcome based on the asymmetry in uncal metabolism. Lateral temporal metabolism did not correlate with outcome. We conclude that both visual PET analysis and quantitative PET analysis predict outcome after temporal lobectomy, although quantitative measures offer more precise information. PMID- 7991122 TI - Bilineal transmission in Tourette's syndrome families. AB - We assessed the frequency of bilineal (from maternal and paternal sides) transmission of Tourette's syndrome (TS) in two groups of pedigrees: (1) 39 high density families in which five or more relatives were reported to have TS, and (2) the families of 39 consecutively ascertained probands referred for evaluation of TS. We used two designations for the TS phenotype (tics, tics or obsessive compulsive behavior [OCB]), and we attempted to verify bilineal transmission with direct examinations. For the high-density pedigrees, bilineal transmission was evident in 33% (considering tics) and 41% (considering tics or OCB) of families, which was confirmed by examination in 77% of the kindreds. For the consecutive pedigrees, bilineal transmission was seen in 15% (tics) and 26% (tics or OCB) of families, which was verified by examination in 66% of the kindreds. Both parents of the proband were affected (tics or OCB) in 38% of the high-density pedigrees and 10% of the consecutive pedigrees. For the high-density families only, the frequency of bilineal transmission appeared to be related to the proband's severity of TS, and for both pedigree groups, the frequency of both parents being affected was higher in families in which the proband's symptoms were most severe. Our findings support the contention that bilineal transmission and homozygosity are common in TS. These genetic phenomena might play a role in determining severity of illness and may explain current difficulties in localizing the gene defect by linkage analysis. PMID- 7991123 TI - Predominance of the adrenomyeloneuropathy phenotype of X-linked adrenoleukodystrophy in The Netherlands: a survey of 30 kindreds. AB - X-linked adrenoleukodystrophy (X-ALD) is an inherited disorder of peroxisomal beta-oxidation associated with accumulation of saturated very long-chain fatty acids, which results in central and peripheral demyelination and in impaired function of adrenal cortex and testes. The phenotypic expression is highly variable, childhood cerebral ALD (CCALD) and adrenomyeloneuropathy (AMN) being the main variants. We explored the 30 Dutch kindreds well known to the Dutch X ALD/AMN Study Group and phenotyped 77 male patients: 35 (46%) had AMN and 24 (31%) CCALD or adolescent cerebral ALD (AdolCALD). These percentages differ significantly from previous reports, in which 25 to 28% of the patients developed AMN and 53 to 57% CCALD or AdolCALD. Our findings indicate that--at least in the Netherlands--AMN may be the most frequent phenotype of X-ALD. PMID- 7991124 TI - Molecular genetics of prion diseases in France. French Research Group on Epidemiology of Human Spongiform Encephalopathies. AB - Human prion diseases are characterized by the accumulation in the brain of an abnormal form of the prion protein. Prion protein polymorphisms seem to play a key role in the pathogenesis of these diseases, probably by enhancing the amyloidogenic properties of the protein. We performed prion protein gene (PRNP) coding sequence analysis in 57 French subjects with Creutzfeldt-Jakob disease (CJD) and found a mutation of the PRNP coding sequence in nine subjects (15.8%); the mutation corresponded with a known family history of CJD in only three of these subjects. In 41 definite and probable cases without known PRNP mutations, codon 129 genotyping revealed an excess of the homozygous 129Met/Met genotype corresponding to a 3.4-fold increased risk of developing CJD when compared with the two other genotypes. We also found that the 129Val/Val genotype, which mainly governs susceptibility to iatrogenic CJD, does not seem to predispose to sporadic CJD. PMID- 7991125 TI - Isolated motor control dysfunction related to progressive multifocal leukoencephalopathy during AIDS with normal MRI. AB - We describe the case of a human immunodeficiency virus-infected 34-year-old man with progressive multifocal leukoencephalopathy (PML). His case displayed unusual features, including a bizarre movement disorder, predominant involvement of the subcortical U fibers on neuropathologic examination, and the absence of MRI abnormalities suggestive of PML. Anatomic-clinical correlations are discussed. PMID- 7991126 TI - Clinical application of the blink reflex with stimulation of the mental nerve in lesions of the inferior alveolar nerve. AB - We evaluated the clinical usefulness of a new modification of the blink reflex (BR) test with electrical stimulation of the innervation area of the mental nerve (MN). We studied the MN BR in 28 patients with traumatic lesions of the inferior alveolar nerve and compared the results with the clinical sensory examination. Within 3 months of the trauma, the MN BR was abnormal in 18 of 20 nerves. In lesions older than 3 months, the test was often normal (in 9 of 11 nerves) despite subjective sensory symptoms and mild clinical signs. Anatomic obstacles to nerve regeneration also gave rise to abnormal MN BR in two patients examined 2 and 4 years after the trauma. The MN BR responses were often absent after violently traumatic lesions, whereas milder injuries commonly produced only latency prolongation of the reflex components. The MN BR is a useful objective method in the diagnosis of sensory loss in the distribution of the MN. PMID- 7991127 TI - The limit of tactile spatial resolution in humans: grating orientation discrimination at the lip, tongue, and finger. AB - The sensory neural pathways serving the lip, tongue, and finger are specialized for spatial information processing; thus, damage to these pathways is likely to be manifested most prominently as a loss of spatial acuity. For that reason, accurate measurement of spatial resolution at these regions is particularly important. The conventional test, the two-point discrimination task, does not measure the limit of spatial resolution and it yields variable results because it does not control nonspatial cues. The aim of this study was to quantify the limits of spatial resolution at the lip, tongue, and finger and to study the repeatability of those measurements using a stimulus that does not introduce nonspatial cues. We employed a grating orientation discrimination test, which has been studied extensively in relation to the underlying neural mechanisms. We obtained psychophysical thresholds for tactile spatial resolution from 15 normal, young adult subjects over seven test sessions. The finest gratings whose orientations were discriminated reliably had groove widths (gratings had equal groove and bar widths) that averaged 0.51 mm at the lip, 0.58 mm at the tongue, and 0.94 mm at the finger. These threshold measurements were highly reproducible between sessions with an overall improvement of 2% per session. These data suggest that the grating orientation discrimination task provides a stable, reliable measure of the human capacity for spatial resolution. PMID- 7991128 TI - Sweat gland vacuoles in Unverricht-Lundborg disease: a clue to diagnosis? AB - There has been no reported pathologic abnormality outside the central nervous system in patients with Unverricht-Lundborg disease (ULD). We report membrane bound vacuoles with clear contents in eccrine clear cells and dark cells in five of seven patients with ULD, as well as in one clinically unaffected sibling. Vacuoles were not seen in the biopsies of two patients and of eight controls with Lafora's disease. These findings, though not entirely specific, suggest that skin biopsy may serve as a diagnostic aid to give supportive evidence for ULD. PMID- 7991129 TI - Adult GM1 gangliosidosis: immunohistochemical and ultrastructural findings in an autopsy case. AB - We report neuropathologic findings for a 66-year-old Japanese man with adult/chronic GM1 gangliosidosis whose main clinical symptoms were speech and gait disturbance attributable to dystonia with rigidity. He was a homozygote for the 51isoleucine (ATC)-->threonine (ACC) mutation in the beta-galactosidase gene. Neuronal loss and intracytoplasmic storage were most prominent in the caudate nucleus and putamen and, to a lesser degree, in the amygdala, globus pallidus, and Purkinje cells in the cerebellum. Other areas of the CNS were relatively spared. We believe that this selective neuronal involvement in the CNS is characteristic of adult/chronic GM1 gangliosidosis and that it reflects a more active turnover of GM1 ganglioside in the affected areas than elsewhere in the CNS. PMID- 7991131 TI - Becker muscular dystrophy with onset after 60 years. AB - We report an unusual example of Becker muscular dystrophy in which the patient was asymptomatic until his mid-60s, and diagnosis was not made until he was 67 years old. The patient had the unusual deletion of exons 3 to 9 within an actin binding region of the dystrophin gene, removal or disruption of which is almost invariably associated with a more severe clinical phenotype. Our case illustrates the danger of drawing conclusions about possibly symptomatic deletions without lifelong follow-up. PMID- 7991130 TI - Altered neurofilament phosphorylation and beta tubulin isotypes in Charcot-Marie Tooth disease type 1. AB - Charcot-Marie-Tooth disease type 1 (CMT1) is associated with atrophy and degeneration of peripheral nerve axons in addition to prominent changes in the structure of Schwann cells. We have investigated the composition of the axonal cytoskeleton in sural nerve biopsies from patients with CMT1. Compared to controls, CMT1 nerves exhibited marked hypophosphorylation of neurofilament proteins and an increased relative abundance of beta tubulin isotypes 2 and 3. Biopsies from patients with other causes of neuropathy, matched to the CMT1 group for severity of axonal atrophy, exhibited an intermediate degree of neurofilament hypophosphorylation and no abnormality of tubulin isotypes. The axonal cytoskeleton in CMT1 resembles that of immature nerve fibers. A failure of normal Schwann cell-axon interaction in CMT1 may prevent full differentiation of the axonal cytoskeleton of myelinated nerve fibers. PMID- 7991132 TI - 1,1'-Ethylidenebis[tryptophan] induces pathologic alterations in muscle similar to those observed in the eosinophilia-myalgia syndrome. AB - 1,1'-Ethylidenebis[tryptophan] (EBT), a derivative of L-tryptophan (LT), is a trace contaminant in batches of LT implicated by epidemiologic evidence in the pathogenesis of the eosinophilia-myalgia syndrome (EMS). We treated female Lewis rats with EBT or unimplicated LT (4 mg per 100 grams daily) by intraperitoneal injection. No rash or weakness occurred in either group. All three EBT rats had a few necrotic muscle fibers. In two rats, perimysium and fascia were abnormally thickened and infiltrated with lymphocytes, macrophages, and sparse eosinophils; two rats had sparse perineurial inflammatory cells. Rats treated with unimplicated LT showed no abnormality. These findings replicate an important feature of human EMS and support the epidemiologic evidence linking EBT to the pathogenesis of the human disease. PMID- 7991133 TI - Gasoline vapors induce severe rhabdomyolysis. AB - A young patient developed rhabdomyolysis after accidentally inhaling gasoline vapors. Although there had been no preexistent myopathy, the caffeine and halothane contracture test classified the patient as being malignant hyperthermia susceptible (MHS). Abnormal contractures also occurred after exposure of muscle bundles to benzine (at 0.01%); in four control tests, benzine-induced contractures (at 0.1%) could be elicited in MHS, but not in normal, muscles. The complex composition of benzine seems to contain potentially hazardous agents that trigger MH. PMID- 7991134 TI - Acute ataxic neuropathy with cross-reactive antibodies to GD1b and GD3 gangliosides. AB - We report a patient with an acute, self-limiting neuropathy consisting of ataxia and areflexia, but without ophthalmoplegia or limb weakness, with transient, high titer serum IgG antibodies to a single NeuAc(alpha 2-8)NeuAc-linked disialosyl epitope, as found on GD1b and GD3 gangliosides. The serum did not react with GQ1b, GT1a, or GT1b. This atypical case, which most closely represents an incomplete Miller Fisher syndrome, indicates that anti-GD1b/GD3 antibodies may be able to induce sensory ataxia. PMID- 7991135 TI - Contralateral control: evolving concepts of the brain-body relationship from Hippocrates to Morgagni. PMID- 7991136 TI - Training guidelines for the use of botulinum toxin for the treatment of neurologic disorders. Report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology. PMID- 7991137 TI - Demyelinating neuropathies triggered by melanoma immunotherapy. PMID- 7991138 TI - Cerebrovascular accident associated with anabolic steroid use in a young man. PMID- 7991139 TI - Parkinsonism exacerbated by paroxetine. PMID- 7991140 TI - Loss of GABAA receptors during partial status epilepticus. PMID- 7991141 TI - Sural neuropathy due to external pressure: report of three cases. PMID- 7991142 TI - Epidural air from a bronchopleural-epidural-cutaneous fistula producing reversible myelopathy and radiculopathy symptoms. PMID- 7991143 TI - Determination of pharmacokinetic drug interactions with carbamazepine and phenytoin using stable isotope labeling and simple high-performance liquid chromatography/ultraviolet detection technique. PMID- 7991144 TI - The case for a descriptive generic nomenclature: clarification of immunostaining criteria for PCA-1, ANNA-1, and ANNA-2 autoantibodies. PMID- 7991145 TI - Multiple sclerosis and trauma. PMID- 7991146 TI - Is hyporeflexia a lower motor neuron sign? PMID- 7991147 TI - Mozart's subdural hematoma. PMID- 7991148 TI - Mozart's subdural hematoma. PMID- 7991149 TI - Bismuth toxicity. PMID- 7991150 TI - Cerebral microembolism. PMID- 7991151 TI - Visual extinction. PMID- 7991152 TI - Down's syndrome and Parkinson's disease. PMID- 7991153 TI - Apolipoprotein E epsilon 4. PMID- 7991154 TI - Apolipoprotein E epsilon 4. PMID- 7991155 TI - Marcus Gunn pupil. PMID- 7991156 TI - [Clinical considerations in Raynaud's phenomenon. How many and which patients are treated?]. AB - Among the multiple aspects about which little is still known about Raynaud's phenomenon (RP), is that, in the author's opinion, regarding the question: how many and which patients are sufficiently troubled by this pathology to seek medical treatment from their own GP or specialist, and what are the results of any treatment commenced. The following questions were put to a group of 180 patients affected by RP attending the out-patient clinic for the first time: 1) how many had already received treatment; 2) which patients were receiving pharmacological treatment and/or had undergone surgery. In this context, the authors assessed the influence of the following parameters on the fact that they had or had not been treated: a) the age of patients; b) the duration of disease; c) the presence of stenosing or obliterating arterial lesions (RP on an organic basis); d) the co-presence of pathologies considered to be the possible etiological cause of RP in literature; e) the severity of symptoms; 3) what results were obtained by medical and/or surgical treatment; 4) what was the course of RP which failed to respond to therapeutic measures. The study examined a series of 180 subjects including 139 (77.22%) females (mean age 47.6% years) and 41 (22.78) males (mean age 42.4 years). Symptoms had been present for a period ranging between 2 and 44 years (mean 10.01). In order to ascertain the possible presence of associated diseases considered by many authors to be causal factors, all patients underwent hemotochemical and instrumental test.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7991157 TI - [Predictive value of the shunt-to-infarct size ratio as a surgical risk factor in patients with decompensated post-ischemic interventricular septal rupture]. AB - Postischemic septal rupture has always been evaluated, in respect of surgical indication, as regards the time lapse between infarct and rupture, interval between rupture and operation, extension of myocardial damage and general risk factors such as age, sex and associated pathologies. But in fact the surgeon is dealing with a two sided problem, the MI and the rupture, and thus surgical results depend upon both the residual ventricular function after MI and the consequences of volume overload on a damaged muscle. Surgical indication could not be based on a single criterion only. Extension of the MI alone is not fully predictive of operative mortality because, aside the reperfusion injury, the repair further jeopardizes viable myocardium and alters ventricular geometry; although the shunt appears unrelated to mortality it certainly interferes with operative outcome at least because of the time elapsed between rupture and repair. So far an index which could correlate the extension of myocardial damage and the entity of the shunt with each other was not available. Patients with septal rupture follow an emergency protocol and are often insufficiently investigated but every patients has a least one echo-Doppler evaluation or even a ventriculography while one or more ECGs are always available. With the presumption that the Qp/Qs is roughly indicative of the right ventricular volume overload and that ecg signs of myocardial infarct are always reliable, we have reviewed among our 24 patients with septal rupture those where a full ecg tracing and a quantitative Echo or angiographic evaluation of the shunt were available.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7991159 TI - [Screening for abdominal aortic aneurysms in the general population. Preliminary results]. AB - Between March 1991 and April 1993, 1188 subjects aged 65-75 years, out of 2734 invited, underwent abdominal ultrasound for screening of asymptomatic abdominal aortic aneurysms (AAA). For each patient the maximal anteroposterior and transverse diameters of the suprarenal and infrarenal aorta were measured. According to the literature data an AAA is defined as an aortic dilatation > 29 mm. AAA < 40 mm are followed by ultrasound every 6 months and the AAA > 39 mm are considered for surgical repair after complete clinical work-up. In addition any aortic dilatation ranging 26-29 mm is followed too, using the same criteria. The aorta was normal in 1112 patients (95.12%), an infrarenal aortic dilatation was found in 21 patients (1.79%), an AAA < 40 mm in 15 patients (1.28%) and an AAA > 39 mm in 21 patients (1.79%). The global prevalence of AAA > 29 mm was 3.07% (0.3% for the females and 6.8% for the males), similar to that reported by other authors. The statistically significant (p < 0.01) risk factors were: smoking, alcohol consumption, coronary disease and chronic lung obstruction. Hypertension and dyslipidaemia were not significant (but HDL-cholesterol and Apo-B), according to a different etiology of the aneurysms. In addition 38.5% of the patients had total cholesterol > 240 mg/dl but only 34.9% of these was under medical treatment and/or on a diet. Our preliminary data confirm the results of similar studies in other countries: screening for AAA is worthwhile on the general population and, looking to a better cost-benefit rate, it might be focused only on males. PMID- 7991158 TI - [Female gender and acute myocardial infarction: what role does it play in the early and late prognosis]. AB - The primary purpose of this study is to examine the influence of the female gender on the early and 1-year post-discharge prognosis after acute myocardial infarction (AMI). Moreover, the therapeutic approaches are compared between the two sexes during the early phase of AMI. We performed a retrospective cohort study of 341 patients, 219 men and 122 women, consecutively admitted to the coronary care unit with AMI. Among the baseline characteristics, the age greater than 70 years, the systemic hypertension and the diabetes mellitus are more represented in women; on the contrary cigarette smoking is prevalent in the male gender. The analysis of laboratory and clinical parameters does not show any statistic differences between the two sexes, except the ejection fraction and the coronary reperfusion. The first turns out to be lower in the females and the second one is more often observed in the males. As for the intra-hospital complications, the cardiogenic shock is prevalent in the female gender, the early mortality gets to 26% in women and 11% in men (p < 0.01). The late mortality during the follow-up does not present any difference between the two sexes. From our data, we conclude that transmural AMI, cardiogenic shock, ventricular fibrillation and 2-3 degree atrio-ventricular blocks are significantly bound to a higher early mortality in women. In them the atrial fibrillation is the only predictor of 1-year mortality. Finally, thrombolysis, beta-blockers and significantly aspirin and heparin (p < 0.05), are less used in the female patients, while diuretics and digoxin are more employed.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7991160 TI - [Correlation of waist-to-hip circumference ratio and cardiovascular risk factors in a population of Southern Italy]. AB - AIM: To evaluate the relationship between body mass index (BMI), body fat distribution and some coronary heart disease risk factors like hyperlipidemia, hypertension and cigarette smoking. STUDY DESIGN: Cross-sectional. PLACE: Tiriolo, a little town close to Catanzaro, of prevalent rural economy. PARTICIPANTS: Volunteers, both males and females, aged more than 30 years and living in Tiriolo. MEASUREMENTS: Body weight and height with subjects in ordinary street clothes and without shoes. Systolic (SBP) and diastolic blood pressure (DBP) by a zero-random sphygmomanometer. Total (TC) and HDL cholesterol (HDL-C) using fingerstick capillary sample technology by a Cholestech analyzer. Waist circumference (W), measured midway between the lower rib margin and the iliac crest, and hip circumference (H) measured at the widest point over the greater trocanthers. Smoking habit by questionnaire. RESULTS: Females had higher values of SBP, DBP, BMI and HDL-C and lower of TC/HDL-C ratio and W/H ratio. Age was similar in both sexes. Females had lower prevalence of hyperlipidemia and cigarette smoking and higher prevalence of hypertension. BMI was strongly associated to blood pressure levels whereas W/H ratio was correlated to TC/HDL-C ratio. CONCLUSION: BMI and W/H ratio give complementary information, useful to assess the cardiovascular risk profile. The simplicity and quickness of these measurements should lead to their large utilization both in epidemiological prevention studies and everyday clinical practice. PMID- 7991161 TI - [Current knowledge and unresolved problems in the pathogenesis of abdominal aortic aneurysm]. AB - This is a wide literature review on abdominal aortic aneurysm (81 references). The main branches in which research is in progress are presented, and new concepts in pathogenesis are illustrated. These come out of the development of knowledge in basic sciences and their interdisciplinary application to this disease. Biochemistry, pathology, immunology, genetics, mathematics, mechanics, fluidodynamics are the routes now followed in the effort to cast light on the inner mechanism of birth and growth of this disease, presently unpredictable and uncontrollable, but successfully treatable by vascular surgery. PMID- 7991162 TI - [Persistent sciatic artery aneurysm. Case report]. AB - Persistent sciatic artery is a rare vascular anomaly particularly interesting for possible complications as buttock aneurysm and ischemic or embolic. Authors describes a case of buttock aneurysm of persistent sciatic artery personally observed analyse its anatomic and clinical features, and lay stress on the importance of angiography as essential examination in order to an exact surgical treatment. PMID- 7991164 TI - Facing round-about the shining cardiac pain myth. PMID- 7991163 TI - [Calcitonin-induced anaphylactic shock. Case report and review of the literature]. AB - A case of anaphylactic shock determined by intramuscular administration of a dose of synthetic calcitonin in a 64-years-old man is described. The patient had not suffered significant cardiovascular events in the past; he smoked twenty cigarettes a day and he was treated with calcitonin for osteoporosis and polyarthrosis. Allergy to diclofenac was demonstrated in the past while preceding administrations of spray calcification didn't provoke side-effects in the patient. Nevertheless after the second i.m. administration of the drug he suddenly fainted. Dyspnea, severe hypotension and maculo-papular erythema were present at the moment of admission to our hospital. The continuous electrocardiogram monitoring showed a characteristic "migrant" ST elevation at first in the anterior leads, then in inferior and septal leads, and premature ventricular and atrial beats. The echocardiographic transtoracic examination proved an apical and septal akinesia which completely disappeared after one hour at a second echocardiographic examination. In spite of intensive medical treatment (lignocaine and hydrocortisone e.v.) the patient had a sustained ventricular tachycardia that quickly degenerated into ventricular fibrillation. After one DC shock at 300 joules we observed spontaneous spontaneous restoration of the normal sinus rhythm. The following clinical evolution was good and no other arrhythmias or cardiovascular symptoms were observed. In order to estimate the reasons of the clinical picture the patient was submitted to serial blood examinations, serial electrocardiograms, exercise stress test, echodypiridamole stress test and serial echocardiograms. The blood examinations showed a relative eosynophilia (3%), the increase of IgE serum level (316 UI) and transient ipokalemia (2.3 mEq/l). None pathological findings were observed in the other examinations.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7991165 TI - [Indications for laparoscopy in the diagnosis and treatment of abdominal trauma]. AB - The use of laparoscopy as a diagnostic method dates back to the first decades of this century. Laparoscopic surgical techniques were first used by gynecologists and later, in 1989, Dubois performed the first cholecystectomy using a laparoscopic approach. Since then, in the space of a few years, there has been an overwhelming spread of videolaparoscopic operating methods, extending the therapeutic possibilities to gastroenterological surgery, as well as to thoracic, oncological, urological, and of course, gynecological surgery. The use of the laparoscope as a diagnostic method in abdominal trauma was proposed in the 70s by a number of authors, but only now, due to technological progress and the constant use of elective laparoscopic surgery, have surgeons been able to use this method for the diagnosis and treatment of patients with blunt or penetrating abdominal trauma. The experience accumulated to date includes a restricted number of cases, but preliminary results are encouraging and it is expected that this method will also be extended to emergency traumatology. The authors' preliminary experience consists of 7 laparoscopic examinations in subjects with abdominal trauma and hemoperitoneum. In 6 patients the examination confirmed hemoperitoneum caused by splenic lesion in 5 cases and hepatic lesion in 1 case. A hematoma of the left mesocolon was observed in one patient and the authors refrained from other treatment. In one subject with a splenic rupture at the ileum it was necessary to convert the operation into splenectomy. In a further 5 cases repeated washing and aspiration were used, using biological necks when necessary, until bleeding had completely ceased.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7991166 TI - [Postoperative course after laparoscopic surgery of the upper abdomen]. AB - Laparoscopic techniques in general surgery have become a widely accepted method, especially for treatment of symptomatic gallstone disease. Many reports have investigated the indications, contraindications, equipment, techniques and outcome of laparoscopic procedures. However, as yet, relatively few studies have discussed the problems concerning patient's monitoring and care during the postoperative course. In the present paper, the authors review the pertinent literature analyzing the management of the postoperative period after laparoscopic surgery of the upper abdomen. Obviously, most data have regarded cholecystectomy, that is the most frequent procedure. Surgical laparoscopists have utilized knowledge deriving from gynecological experience, but these procedures are generally short and performed on young, otherwise healthy female patients. On the contrary, laparoscopic digestive surgery shows both gastrointestinal and peculiar general problems. These procedures are frequently performed on older patients who may have pre-existing diseases and require longer periods of peritoneal insufflation. During surgery of the upper abdomen, the pneumoperitoneum and the patient's operative position produce haemodynamic and respiratory changes coupled with acid-base disturbances. Intraabdominal hypertension causes a venous stasis along the inferior vena caval territory that can lead to a decrease in cardiac preload and in cardiac output. Usually, a compensatory increase in peripheral vascular resistance ensures normal or mildly high values of arterial tension. Furthermore, a hypercapnia and a mild mixed acidosis can develop as a result of the concomitance of different pathogenetic factors.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7991168 TI - [Specific complications in laparoscopic cholecystectomy: 610 cases]. AB - The authors report their experience of 610 cases of laparoscopic cholecystectomy (VLC) and focus attention on the specific complications of this operation, in other words those not linked to the access phase (pneumoperitoneum and introduction of the trocars). The total percentage of complications reported was 1.3%. The most frequent complication was hemorrhage (0.6%), a finding which is in line with international literature. It is emphasised that complications almost always occur postoperatively, sometimes after the early discharge of patients and for this reason they may be more severe. The importance of an accurate dissection of the cholecystic ileum is underlined as being the only real guarantee against lesions to the common bile duct. In overall terms, however, after appropriate training and under the guidance of an expert surgeon, VLC may be considered as the new "gold standard" for treatment of cholelithiasis. PMID- 7991167 TI - [Laparoscopic cholecystectomy. Personal experience]. AB - Personal experience in the treatment of 120 patients submitted to laparoscopic cholecystectomy from March 1992 to September 1993 is presented. The good results obtained suggest that VLC is the best surgical approach for the treatment of cholelithiasis in reason of diminished pain after surgery, shortened hospital stay and early return to work. PMID- 7991169 TI - [The colorectal restoration. When should it be done?]. AB - The authors report a series of 10 reconnections, 4 after Hartmann operations for cancer, 3 after Mikulicz for diverticular disease, 1 after Hartmann for diverticular disease, 2 after Hartmann for traumatic perforation of sigma. Neither surgical complications nor death are reported. To reduce the risk of complication it is necessary to execute colorectal restoration with careful fiming. After the Hartmann operation you must operate in the shortest time. After operations for diverticular disease, you must operate after the lowest period of 6 months. PMID- 7991170 TI - [Perforated colonic diverticulitis. Surgical technique]. AB - Emergency surgery is required for performed colonic diverticulitis. Surgical indications are not uniform in literature. In the experience of the authors the operations have been performed in the case of peritonitis subsequent to the perforation or in the case of failure of the conservative treatment. Twenty-four patients underwent surgical intervention because of diffuse (17 cases) or localized peritonitis (7 cases). Exitus were related to cardiovascular complications in patients over seventy. Postoperative results are related to the age, the general conditions of the patient and to the intraoperative finding, of localized or generalized peritonitis. Operations may be divided into two groups: conservative procedures or primary resections. In the first one it is possible to suture the colonic wall without resection; in the second one the intraoperative finding or the extensive necrotic lesions indicates colonic resection or exteriorization. The surgical treatment adopted is correlated both to the age and cardiorespiratory conditions and to the other associated diseases. PMID- 7991171 TI - [Solitary ulcer of the rectum]. AB - The authors review their five-year experience of solitary rectal ulcers. A revision of the most recent literature enables them to outline the characteristics of the disease with reference to its epidemiology, anatomopathology and clinical features. The discussion focuses on the problem of treatment which must be based on a thorough and in-depth knowledge of pathogenetic mechanisms. The paper outlines two theories, the hamortomatous one and the so-called mechanical theory involving the hinge valve, which are referred to by most researchers. The question of treatment is then discussed illustrating the possibility of resorting to surgical-type treatment which appears to be the most suitable for the definitive resolution of the problem. But since, at least in the light of the authors' personal experience; the majority of patients belong to an age group in which other pathologies are often present, the medical treatment option appears to be more rational. The re-education of the alvus achieved using suggestions not only of a dietary type but also regarding the behaviour and correct position to assume during defecation appears, at least theoretically, sufficient to obtain a marked improvement. The local application of therapeutical AIDS, if necessary strengthened by the action of drugs taken systemically, brings considerable further benefit to the patient who cannot and/or does not which to undergo surgery. PMID- 7991172 TI - [Surgery of the kinking carotid artery]. AB - Forty-three kinkings of the epiarotic vessels were observed at the Istituto di Chirurgia Generale e Cardiovascolare dell'Universita di Milano from January 1st 1971 through July 31st 1992. Six subjects were admitted for a history of one or more transient ischemic attacks. In four cases surgical resection of the kinked tract of the internal carotid and end-to-end direct reconstruction was carried out, completed by carotid bifurcation endarterectomy in three, where atherosclerotic carotid disease was severe. All the reconstructions are currently patent and no neurological symptoms were recorded at follow-up; 39 cases were treated conservatively by antiplatelet therapy and controlled each six months: to date no worsening of the echocolordoppler imaging of the lesion was noted, and all these subjects remained completely asymptomatic. The authors point out that correct clinical approach to carotid kinking is a conservative one: surgical operation must be performed only in those subjects affected with cerebral ischemic attacks not justified by other diseases. PMID- 7991173 TI - [External saphenous vein excision with mini-phlebectomy]. AB - The surgical treatment of the varicosities of the short saphenous vein is one of most controversial matter of modern phlebology. The anatomy of this vessel, that is deep, and is accompanied by the sapheno external nerve, can be very varied species for that which concerns the sapheno popliteal joint. The traditional surgery as the sclerotherapy exposes the patient to risks and failures. For such reasons the authors believe that the modern technique of stab evulsion phlebectomy could be formatted like the treatment of choice of the venous pathology of the short saphenous vein. Synthesizing, the stab evulsion phlebectomy consists of the removal of the varicosities of the lower limbs through incisions of the skin of 1-3 mm using special surgical instruments with hook (Chrochets). The technique doesn't foresee neither stitching neither vascular binding, and could be performed on local anesthesia and in ambulatory regimen. The results of the technique and the absence of complications suggests its adoption of principle in the treatment of the incompetence of the short saphenous vein. PMID- 7991174 TI - [Considerations in immediate and delayed breast reconstruction]. AB - The authors evaluate the different procedures for breast reconstruction in order to determinate the best indication of each technique. From January 1983 to June 1992, 196 reconstructions for breast cancer using implants, including 100 immediate and 96 delayed, were performed. Different types of breast implants were used in this period: in 1983-84 46 double lumen prostheses were performed, in 1985-86 34 Radovan temporary tissue expanders, from January 1986 to June 1991 115 Becker and Gibney permanent tissue expanders and 8 microstructured prostheses. Due to unavailability of silicon-gel implants, from January to June 1992 12 breast reconstructions with saline temporary tissue expanders were performed. In the patients with radical mastectomy 39 latissimus dorsi muscular flaps were carried out for implant coverage. In the same decade 204 breast reconstructions using Rectus abdominis myocutaneous (TRAM) flaps, including 201 delayed and 3 immediate were performed. It can be concluded that the implants are first choice for small or medium size breast, with light ptosis, in immediate reconstruction and when the patients refuse harder surgical procedures. On the contrary the autologous tissue, such as TRAM flap, can be used in patients with redundant abdomen, with controlateral large and ptotic breast and in delayed reconstruction. PMID- 7991175 TI - [Personal experience in treating bilateral inguinal hernias]. AB - The treatment of bilateral inguinal hernias is an operation which has a high failure rate. This operation is influenced by a number of factors, above all the strain on aponeuroses and muscle fibres during reconstructive plastic surgery. In addition, metabolic factors, the advanced age and in particular surgical infections should also be taken into account. Over the course of past years synthetic prostheses have been introduced for hernia treatment (tantalum, nylon, steel, ivalon); currently, polypropylene, dacron and goretex are used. Placement may be intraperitoneal, preperitoneal and prefascial. The authors report their experience from December 1989 to December 1991 in relation to 70 patients undergoing surgery for bilateral inguinal hernias. The following results were obtained: a low percentage of complications, reduction of costs and no recidivation to date. These results enable the authors to affirm that the use of synthetic mesh for the treatment of bilateral inguinal hernias is the most appropriate method of choice. PMID- 7991176 TI - [Isolated hyperthermic antiblastic perfusion in recurrent melanoma of the extremities]. AB - Twenty-two patients with recurrent melanoma of the limbs, underwent Hyperthermic Antiblastic Perfusion (HAP). HAP lasted 60 min, with maximal local temperature of 40.5-42 degrees C and melphalan 10 mg/L limb volume as antiblastic agent. Fourteen patients had in-transit metastases and 8 local recurrences. Regional nodes were involved in 6 patients. Systemic leakage monitored with 125I or 99Tc ranged between 5 and 30% (mean 19%). No operative mortality nor major complications occurred. Local toxicity scored Wieberdink grade I in 6 patients, grade II in 11 and III in 5. Response rate (UICC) in the 9 patients treated with unexcised lesions was 88% (55% complete responses). After a median follow-up of 27 months (1-92) 9 patients relapsed after a median time of 17 months, and 15 patients are currently disease free, 4 of them being re-excised and one reperfused. Actuarial 5 year survival is 67%, with 45% disease free to the first relapse. Our results are consistent with the literature indicating HAP as a safe procedure with a high evidence of clinical responses. PMID- 7991177 TI - [Continuous suture in laparotomy using an absorbable eyelet thread according to the Smead Jones technique]. AB - In 78 patients undergoing laparotomy suturing was carried out using absorbable thread (polyglyconate - Maxon) with eyelet to obtain a continuous knot-free suture according to Smead Jones' technique. A prospective study was made of all surgical wounds three months after the operation to evaluate the reliability of this technique. On examination, wounds were fully healed in 98% of patients. Less than 2% of patients revealed infections, dehiscence or anomalous granulations of the wound. No laparocele were observed at the time of control using this method. Continuous suture using a trimethylene polyglyconate (Maxon) thread with eyelet according to the Smead Jones technique was found to be safe and effective. A follow-up after a longer interval will be performed in this group of patients in order to confirm these conclusions. PMID- 7991178 TI - [Assessment of phonation in patients after oncologic surgery of the oral cavity]. AB - The authors evaluated word articulation ability in 33 patients undergoing integrated (chemo-radio-surgical) treatment for carcinoma of the oral cavity. Speech was intelligible in 22 patients. Severe language distortion was observed in 11 patients. PMID- 7991179 TI - [Major resection in severe hepatic trauma. Technical indications and clinical considerations in a case of personal experience]. AB - Before the Second World War overall mortality from liver injuries was 60%. The extraordinary progresses made in elective hepatic surgery, backed by an increasingly detailed physiopathological knowledge and by progress in anesthesia and reanimation techniques, have had a positive effect also on traumatological liver surgery bringing mortality rates dawn to between 10% and 20%. However, in spite of this reassuring success, mortality from liver injury still remains unacceptably high for the most severe lesions on the "Calne scale", in particular 50-60% for 4th degree lesions. A review of the literature regarding this group of patients indicates hemorrhagic shock as being the prime cause of mortality: extensive lobar disintegration associated with severe vascular disinsertion involving the suprahepatic-caval crossroads are responsible for the patient's death in 50% of cases. Associated intra- or extra-abdominal lesions, which are often commonplace, make a decisive contribution to raising the mortality rate for 4th degree lesions. Lastly, the high number of possible postoperative complications contributes to the severity of prognosis in this group of patients. The analysis of a case of severe hepatic injury (4th degree according to Calne's and Lenriot's classifications) with a favourable outcome prompts the author to make a number of clinical and surgical observations, and to conclude that emergency hepatic resection still continues to be a rare indication reserved for cases of absolute necessity for which there is no other possible therapy. PMID- 7991180 TI - [Entero-vesical fistula in Crohn's disease. A case report]. AB - A case of entero-vesical fistula in Crohn's disease is presented. Clinical manifestations, diagnostic means and surgical treatment of the lesion are discussed. PMID- 7991181 TI - [Spontaneous pneumoperitoneum. Two case reports]. AB - The author reports two cases of spontaneous pneumoperitoneum subjected to a laparotomy without evidence of intra-abdominal damage. Spontaneous pneumoperitoneum is a clinical situation caused by favourable, abdominal or extra abdominal, conditions in association or otherwise with symptoms. Suspicion of this situation is asymptomatic patients with pneumoperitoneum and a rigorous clinical check can avoid unnecessary laparotomies. PMID- 7991182 TI - [Epithelioid hemangioendothelioma of the liver. A case report]. AB - One case of epithelioid hemangioendothelioma (EHE) of the liver is reported. The problems of a correct diagnosis of this unusual type of vascular tumor are discussed. A final diagnosis can be established only by histologic examination of appropriate material and may be helped by immunohistochemistry and ultrastructural examination. Tumor cells are vasoformative and synthesized Factor VIII-related antigen. The accurate diagnosis of EHE of the liver is of clinical and therapeutic relevance, for the favourable prognosis, also without therapy, nevertheless liver transplantation represents in selected cases (patients exhibiting a rapidly progressive liver failure) the only possible treatment. The case studied in our Department is very interesting, because it represents a summary of knowledge regarding this type of neoplasm in a 20-year period. PMID- 7991183 TI - [Transduodenal sphincterotomy and type II Mirizzi syndrome]. AB - This paper describes the clinical course of a 76-year-old woman surgically treated in our department (General Surgery) for obstructive jaundice in Mirizzi syndrome (II). Ultrasonography and ERCP failed to demonstrate the pathological situation at the level of the biliary tree. When laparotomy was decided because of the progressive worsening of the general clinical conditions of the patient, intraoperative cholangiography showed the presence of a cholecystocholedochal fistula with multiple residual stones eroded into the common bile duct. Surgical management consisted of partial cholecystectomy, removal of the stones, choledochoplasty and exploration of the distal part of the common bile duct by a transduodenal sphincteroplasty. The post-operative period was uneventful and the patient was discharged from our department nine days after surgery. Even though the surgical approach to Mirizzi syndrome generally includes procedures other than papillosphincteroplasty+partial cholecystectomy, our experience seems to substantiate the efficacy of the previously mentioned treatment under suitable conditions. PMID- 7991184 TI - [Acute pancreatitis in pregnancy treated with somatostatin. A case report]. AB - A case of acute pancreatitis in the second trimester of pregnancy is described. The literature shows a maternal mortality of 37% on and a perinatal mortality of 37.9%. Medical management with somatostatin was conducted, in addition to usual therapy. The result was positive; the patient was delivered by cesarian section at term of pregnancy. The newborn showed normal anthropometric measures. PMID- 7991186 TI - [Is surgery duration really a complication factor?]. AB - Of the numerous factors which may cause postoperative complications, some authors sustain that the durations of surgery plays a fundamentally important role. On the basis of a retrospective survey and analysis of cases operated, the authors observe that this factor, if considered alone, does not appear to cause a significant increase in septic complications, anastomotic dehiscence or mean postoperative hospital stay. Four homogeneous groups of patients were examined. Two groups included 100 who had undergone abdominal surgery which had not contaminated the peritoneal cavity. The other two groups included 150 patients who had undergone partially polluting colorectal surgery. The general preparation of patients was similar, with the exception of antibiotic prophylaxis. The mean time was calculated by analysing anesthesiological records. From an analysis of the most recent data, which are characterized by the absence of anastomotic dehiscence and operative mortality, it can be seen that the incidence of sepsis has fallen to 4% even if mean operating time was long. Mean postoperative hospital stay was also reduced from 17.3 days to 13 days. The prolongation of operating times does not depend on the complexity of surgery, intraoperative complications or the surgeon's inexperience, but may be the result of the meticulous implementation of procedures and steps taken to prevent complications which, given that they require extreme care and attention, necessarily contribute to increasing the duration of surgery. With regard to antibiotic prophylaxis and the duration of surgery, it was observed that if antibiotic prophylaxis preceded the operation by more than one hour, the incidence of sepsis was about 20%. If treatment coincided with the induction of anesthesia or the start of surgery, then the incidence of sepsis fell to 13%.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7991185 TI - [Acute ischemia of the upper limb. Clinical case and general considerations]. AB - The authors report a case of acute inveterate right subclavian artery obstruction. The leading role of US vascular investigation and the surgical technique adopted are pointed out. The personal findings are compared with those from the international references. PMID- 7991187 TI - [Lesions of the spleen caused by blunt trauma. Proposal of a classification based on CT and correlation with prognosis and treatment]. AB - The use of CT scan has had a profound influence on the evaluation and treatment of closed abdominal injuries, enabling a progressive reduction to be achieved in the total number of emergency laparotomies. The authors review CT performed over the past two years in adult hemodynamically stable patients with traumatic splenic lesions. In 19 cases it was possible to commence non-surgical treatment which was successful in 18/19 cases. A simple and precise scoring system was elaborated on the basis of data obtained from CT by evaluating 4 parameters: extent of free intraperitoneal effusion, concomitant lesions to other abdominal organs, severity and site of splenic lesion. This classification gives a high degree of prognostic accuracy and provides a useful guideline in the choice of the most appropriate treatment. PMID- 7991188 TI - [Surgical treatment of diverticular disease of the colon. Our experience in the last decade]. AB - The authors analyse their personal experience of diverticular disease of the colon and, comparing it with that of other authors, draw attention to some fundamental data relating to the type of management chosen. Having underlined the high incidence of disease in relation changed living conditions, the authors point out that this pathology is becoming more frequent as a result of the increased average age and that subacute and acute clinical manifestations of the disease are also more common-place. Attention has often been drawn to the presence of non-evolved phlogistic symptoms which it is possible to treat medically thus enabling the operation to be postponed in some cases to a time which is more convenient for the patient, whereas in other cases it has resulted in the remission of symptoms. Surgical therapy need not be used in "silent" cases, but is obligatory in recurring or complicated forms. The authors also affirm that surgery is not burdened by particular postoperative complications which, if present, are linked essentially to peritonitis due to perforation or to other associated pathologies. The use of mechanical staplers has also restricted the number of derivative operations and those performed in several stages. PMID- 7991189 TI - [Urogenital sequelae in surgery of rectal carcinoma]. AB - Seventeen consecutive patients with rectal cancer underwent surgery at our institution between January 1988 and December 1990. The aim of this study was to assess the urogenital symptoms after radical resection of the rectum. Ten of these patients were suitable for the study, 9 of whom had an Anterior Resection (with colorectal anastomosis in 7 cases and with coloanal anastomosis in 2) and 1 a Miles operation. We observed urogenital disturbances in 2 patients (20%), 1 male with urinary tract dysfunction and 1 female with difficulties of sexual activity. The disease-free interval, at 36 months, was 100%. We suggest that curative surgery for rectal cancer can be associated, in overall cases, with a low incidence of urogenital disturbances. This allows the improvement of quality of life without evidence of loco-regional recurrence. A resective approach of rectal cancer, able to preserve nervous fiber of pelvic plexus but providing at the same time a radical excision of the tumor, seems to be a determining factor. PMID- 7991191 TI - [Use of mechanical staplers in biliopancreatic diversion intervention]. AB - The use of mechanical staplers in general surgery and in particularity in biliopancreatic diversion (BPD) has led to a marked reduction in the duration of surgery, thus requiring shorter anesthesia times. In obese subjects this also serves to reduce the risks related to their particular clinical and metabolic conditions. The authors report their experience in 53 patients; in 26 cases automatic linear staplers were used to create the ileal-duodenal and gastric tomy only, whereas the entero-entero anastomosis and gastro-entero anastomosis were performed manually using a biliopancreatic diversion technique. In the remaining 27 cases the operation was performed exclusively using automatic staplers. The paper then examines the complications arising from the use of mechanical staplers, dividing them into early and late. Among the first were two episodes of GEA hemorrhage (7.4%) and an asymptomatic fistula again of the GEA (3.7%). The late complications only included two stenoses (7.4%) of the GEA, both resolved using endoscopic pneumatic dilation. PMID- 7991190 TI - [Benign obstruction of the common bile duct: what is the current role of transduodenal sphincteroplasty?]. AB - This paper is a critical review of the clinical records of 20 patients who underwent a Transduodenal Sphincteroplasty (PSP), from October 1990 to January 1992 at our Department (General Surgery). The age was 64.9 (14.2) years (mean and standard deviation), but 14 (70%) of those patients were older than 60 (range: 63 to 89) and 9 (45%) were in the 8th up to 9th decade of their lives. In 16 patients PSP was performed at the same time as cholecystectomy. Common bile duct (CBD) exploration was decided in 11 patients only on the basis of the intraoperative cholangiographic findings (evidence of CBD stones and/or benign stenosis of the Papilla of Vater) as demonstration of the permanent role of this examination in biliary surgery. Among the patients who underwent PSP some time after cholecystectomy, one had a lesion of the choledochus, sustained when he was cholecystectomized 15 days before. Because of the fact that recovery was prompt and definitely uneventful, PSP together with the infusion of somatostatin (SMTN) can be considered a useful approach to the treatment of the biliary fistula. PMID- 7991192 TI - [Care of the patient after biliopancreatic diversion (BPD) surgery]. AB - The authors report their experience in the care of severely obese patients undergoing biliopancreatic diversion (BPD) surgery. The success of this surgical technique not only depends on its correct application but also on correct postoperative management, both immediately and over time. After a short summary of the methods of management used immediately after surgery, the authors focus in greater detail on the most frequent complications in this type of surgery: these are divided into early and late. Among the former, the authors discuss thromboembolic disease, the most severe complications and bronchopneumonia disorders. The authors illustrate the methods of treating both as well as therapies for their prevention. The most frequent and potentially dangerous late complications are examined in detail: protein malnutrition, sideropenic anemia and diarrhea. Lastly, the authors underline the need for a constant rather than episodic approach to the problem of severe obesity since, in their opinion, only continuous and long term application ensures the best results with the fewest complications. PMID- 7991193 TI - [Gallbladder carcinoma. Our experience]. AB - Carcinoma of the gallbladder is the most frequent neoplasm of the biliary tract. During the period between 1 January 1979 and 31 December 1991 a total of 1016 operations for cholecystectomy were performed by our Division of Surgery and 27 cases of gallbladder carcinoma were diagnosed. The symptoms were generally similar to those of benign hepatobiliary disorders. The diagnostic tests carried out did not allow a preoperative diagnosis of gallbladder carcinoma to be made. In the majority of cases diagnosis was a surprise following the histological analysis of the operated part. The prime therapy for these lesions is surgery. Since it is not possible to make an early diagnosis of this type of neoplasm, which in the majority of cases has a fatal prognosis, the authors consider that the finding of inveterate calculosis, large calculi and echographic thickening of the gallbladder wall represent indications for surgery even in the absence of major symptoms. PMID- 7991194 TI - [Carcinoma of the gastric stump. Our experience]. AB - The authors have examined eight patients operated at the Department of Surgery "B" of the G. Bosco Hospital (Torino) from 1980 to 1992 for gastric stump cancer. All patients were male of about 72 years who were subjected to resection: 5 for gastric ulcer and 3 for duodenal ulcer. During the first operation they used the same recanalization technique after gastric resection: the semi-oral distal gastric jejunal anastomosis created by Hofmeister-Finsterer. The second operation was the subtotal gastric resection made on 6 patients, total gastrectomy in 1 case and explorative laparotomy in an inoperable case. The average of free time from disease was 32 years while it is 24 years in literature. The mean survival was 40 months. The 5-year survival was about 33%. The authors conclude that carcinoma of the gastric stump has a worst prognosis then carcinoma in normal stomach. The subtotal resection has the same results as in total gastrectomy. PMID- 7991195 TI - [Emergency surgery in patients over eighty]. AB - The authors describe a series of 139 over-eighty patients (M = 53, F = 86), who underwent emergency surgery between 1-1-1987 and 30-6-1993. They consider diagnosis, copathology, type of surgical procedures, postoperative complications and final results. In this series they study 73 large bowel obstruction and 48 peritonitis. They notice important copathologies in 78% of patients, in particular cardiovascular diseases. They performed 74 mayor surgical procedures with 48% of postoperative complications and exitus in 24% of cases, due overall to exacerbation of coexisting diseases. The authors underline the direct between mortality rate and number of copathologies, and analyze the basic rules to follow in surgical indications and during the postoperative period. PMID- 7991196 TI - [Video-assisted mediastinoscopy. A new application of television technology in surgery]. AB - Since 1959, when mediastinoscopy was introduced by Carlens, the practice has been technically unchanged. The authors suggest how the new video technologies could be very helpful to this procedure leading to an ergonomic position for the operator and a faster performance. Initial experience is reported. PMID- 7991198 TI - [Iatrogenic lesions of cranial nerves during endarterectomy of the carotid artery]. AB - Cranial nerve injuries may result from carotid endarterectomy. In a retrospective study of 222 surgical procedures, from July 1982 through June 1990 only three cranial nerve injuries were documented (1.35%). In a prospective study of 79 carotid endarterectomies performed from July 1990 through June 1992, there were 11 nerve injuries (13.9%), fortunately most of them were temporary. We conclude that carotid endarterectomy is associated with a much higher incidence of local nerve injury than retrospective surveys would indicate. PMID- 7991197 TI - [Incidence and treatment of vascular prosthesis infection in the groin. Personal experience]. AB - The incidence of prosthesis infection in the groin ranges between 1 and 3%, with high morbidity and mortality rates. Contamination, irrespective of whether it is endogenous or exogenous, may occur during surgery of afterwards due to a secondary bacterial load which is often associated with a traumatic surgical technique for tissues, often in emergency surgery or re-operations. MATERIALS AND METHODS. Over the past 5 years a total of 410 prosthetic alloplastic grafts have been made by our Division of Vascular Surgery with at least one anastomosis at an inguinal level. The materials used for prosthesis were dacron and PTFE. Thirty one infections were observed in the groin of which 11 involved the prosthesis and 20 were apparently restricted to the superficial and deep layer of the dermis. A cell culture test and antibiogram was always performed. Surgical or medical therapy (loco-regional + general) was used according to individual cases. RESULTS. With regard to the 11 patients with manifest infections of the prosthesis, only trans-obturator bypass surgery gave positive long-term results, whereas other operations (femoro-femoral bypass, axillo-popliteal bypass) were not satisfactory. Of the other 20 patients treated using loco-regional and general medical therapy, 9 developed pseudo aneurysm over time for which it was then necessary to resort to surgery. DISCUSSION AND CONCLUSION. Currently there is no universally accepted treatment protocol for the management of prosthesis infection. However, it is generally considered useful to isolate any pathological agent (using routine biopsies of arterial wall or thrombo-endoluminal fragments during the primary operation) before infection can develop so as to be able to commence specific antibiotic therapy. In this context the authors underline the more devastating action of some bacteria (pseudomonas, Staphylococcus aureus) in comparison to others (Staphylococcus epidermidis). Turning to therapeutic measures, when there are anatomical grounds and with the greatest possible respect for periarterial tissues, it is considered that trans-obturator bypass is preferable in the presence of manifest infection of the prosthesis, whereas medical therapy can be used (loco-regional + general) if infection is limited to the surface layers of the inguinal area. Possible complications over time may be corrected using surgery and in situ reconstruction if infection is no longer present. PMID- 7991199 TI - [Extra-anatomic bypass]. AB - The authors describe their experience on extra-anatomic bypass effected in five years at their Hospital. This note assesses indications relative to rebuilding operations of this kind (in particular distal revascularization in patients at high risk, or as secondary operations at prosthesis infections), the complications that can derive and finally the series in our Hospital in the years between 1986 and 1991. In our experience axillo-mono, bi-femoral and femoro femoral bypass have been effected getting excellent results, so we believe that these operating techniques should also be extended to younger patients and to patients with arteriopathies to the late second stage of Leriche-Fontaine. PMID- 7991200 TI - [A retrospective study on the importance of preoperative control in the prognosis of spinocellular carcinoma of the oral cavity]. AB - Surgical treatment of advanced forms of spinocellular carcinoma of the oral cavity (stages 3-4) has been integrated for a number of years with cycles of chemo- and/or radiotherapy both before and after surgery. This chemo-radio surgical therapeutic protocol consists of four distinct stages, separated by precise treatment-free intervals, which enable the best efficacy to be achieved through synergy. A total of 60 patients were treated by our Ward using this protocol during the period March 1988-June 1992. At the time of surgery a complete negative outcome in the histological picture (pTO) was observed in 40% of cases; lesions had not regressed on only 16% of patients. A retrospective type study has been carried out using Kaplan-Meier's statistical analysis to evaluate the prognostic factors in this population: a significant correlation was found between disease-free time and survival, calculated at 40 months from the completion of the protocol, and histopathological TNM. Non correlation was found with clinical TNM: therefore, rather than the extent of the lesion at the time of diagnosis, its control during preoperative stages appears to be the major prognostic factor. PMID- 7991201 TI - Antibiotic prophylaxis in elective neurosurgery. Epidemiological study. AB - The authors present an epidemiological study of patients who have undergone elective neurosurgery and who have been treated with different types of antibiotics throughout a ten year time span. From the statistic analysis of the different parameters taken into consideration (administering modalities of the short-term and long-term antibiotic, type of sepsis encountered, isolated microorganisms) the authors show, as a result, that the long-term antibiotic prophylaxis is a clearly improper method; the short-term prophylaxis is a correct method the effect of which is, however, still controversial as it does not modify a natural low percentage of infections in elective neurosurgery. The role given to the antibiotic seems much less important compared with the adoption of correct antiseptic measures and of proper nursing. PMID- 7991202 TI - [Organization of a center for prevention and treatment of obesity]. AB - Obesity, a pathology with a multifactorial etiopathogenesis currently has an incidence of around 6% in the adult population in Italy. Considering that this disease provokes a statistically significant reduction of life expectancy, there is an evidence need to create structures which can deal with this problem. For this purpose, the Centre for the prevention and cure of obesity was set up by the Department of Surgery and Anatomy at the University of Palermo in 1990. It makes use of the specialist skills of experts in internal medicine, dieticians, cardiologists, psychologists and surgeons. In particular the authors give a detailed description of the diagnostic iter used and the methods of follow-up adopted for patients undergoing biliopancreatic diversion (BPD) surgery. In conclusion, the authors emphasize the need for a multidisciplinary approach to this pathology since this is the only way of minimizing complications arising during BPD surgery and obtaining the best results. PMID- 7991203 TI - [Errors in digestive surgery. A case of tension pneumothorax during laparoscopic cholecystectomy]. AB - A case of tension pneumothorax caused by an accidental diaphragm injury during laparoscopic cholecystectomy is presented. This complication occurred during one of the first laparoscopic cholecystectomies caused by the crochet abandoned for few seconds, into the peritoneal cavity. Therefore laparoscopy was performed and diaphragm injury repaired. PMID- 7991204 TI - [Combined use of Stoppa's and Rives' techniques in multiple eventration]. AB - A patient with a complex pathology of the abdominal wall underwent an operation done by the simultaneous combination of Rives' and Stoppa's prosthetic techniques. The absence of complications and perfect staying power of the wall seems to confirm the efficacy of this surgical procedure. PMID- 7991205 TI - [Internal hernias. Description of 2 cases]. AB - The authors describe two cases of recent observed internal-hernia, regarding in the first case the right para-duodenal dimple, and in the second a mesenteric breach. They report the clinic presentation and the diagnostic and therapeutic approach compared with the data deriving from the international literature. A complete clinical classification of the internal-hernia is illustrated showing the different clinical signs. The respective symptomatology that in the initial phases of this pathology is not too evident, shows that the internal hernia should always be held in due consideration at the moment of diagnosis because the consequent mortality due to complications such as intestinal-gangrene is rather high. PMID- 7991206 TI - [A rare cause of intestinal pseudo-obstruction: Ogilvie's syndrome]. AB - The authors report four cases of Ogilvie's syndrome, a rare cause of intestinal pseudo-obstruction. After having reviewed the pathogenetic hypotheses reported in the international literature, the authors describe the symptoms, diagnostic iter and conservative and surgical management. With regard to the latter, the authors report their own experience which differs from that reported in the literature since they advocate the use of intraoperative colonoscopy for both decompressive and diagnostic purposes, the use of the cecal fistula instead of mid-canal cecostomy, and the application of a multi-fenestrated endocolic probe inserted through the anus and as far as the left colic angle for further decompressive purposes. PMID- 7991207 TI - [Lipoma of the small intestine as a rare cause of intestinal occlusion]. AB - Lipoma is a benign tumour of mesenchymal origin which is not frequently localized in the gastroenteric tract; in anatomopathological statistics it is less rare: this is due to the fact that it rarely reaches dimensions which warrant surgical treatment. It is usually either an occasional finding during the course of laparotomy due to other motives or is the cause of complications, as in the present case of intestinal occlusion due to ileocolic invagination, resulting in emergency surgery. As a cause of occlusion tumours of the small bowel are second in terms of incidence to adhesive factors, volvuli and hernias. Invaginations account for 2/3 of small bowel occlusions caused by up to 80% of tumours: the lipoma is the most frequent benign tumour to cause invagination in its submucous polypoid and more or less scissile form. Symptoms are not specific and this causes a delay in diagnosis. Patients are often young subjects with a history of recurrent abdominal colic and sensitivity to anti-spastic drugs so much so that in the past they were diagnosed as "chronic colic" sufferers. Sometimes the only symptom is dyspepsia, or nausea and vomiting, or occasionally abdominal distension with constipation or attacks of diarrhoea. Radiology is not of great value in the diagnosis except for indicating the possible need for emergency surgery. There are no radiological tests, with or without contrast mediums, echography, CAT or MNR which can diagnose this pathology. The decision to operate is usually triggered by the presence of a complication, but perioperative extemporary histological tests are advisable for a correct surgical approach: if the form is scissile, segmentary resection of the small bowel is necessary.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7991208 TI - [Acute abdomen caused by eosinophilic gastritis]. AB - The authors describe a case of acute abdomen operated in emergency for obstruction in a patient with eosinophilic gastritis. This is very unusual pathology characterized by eosinophilic infiltration of the gastric antral wall combined with peripheric eosinophilia. This particular case was operated for a small bowel obstruction but in those rare cases, when we can reach a diagnosis with endoscopic biopsy, a prudential attitude becomes inevitable as this pathology is very responsive to medical treatment with corticosteroids. PMID- 7991209 TI - [Diverticular disease of the vermiform appendix. Anatomo-clinical observations]. AB - The authors describe a case of diverticular disease of the appendix. The diagnosis is intraoperative and histological while therapy is based on surgical treatment. The authors seem to be favorable to surgical treatment in case of diverticulosis of the appendix in order to avoid dangerous complications. PMID- 7991210 TI - [Revascularization syndrome in traumatic vascular lesions of the limbs]. AB - The authors report a case of severe revascularization syndrome which occurred following traumatic vascular lesion to a lower limb. They focus attention on the mechanisms which make this syndrome more frequent and more severe in traumatic lesions as opposed to that observed following acute arterial obstruction secondary to embolism or thrombosis. PMID- 7991211 TI - [Anatomo-clinical considerations on intrahepatic calculosis]. AB - After reviewing the anatomoclinical classification of intrahepatic lithiasis, the authors underline the need to perform hepatic resections in selected cases. The case reported is an example of the indications for this type of surgery. PMID- 7991212 TI - Urachal adenocarcinoma. A case report. AB - A 21-year-old woman, previously operated for an acute abdomen from an infected urachal cyst, developed an urachal carcinoma. The importance of systematically and completely exciding urachal cysts is stressed by clinical considerations of the uncommon neoplasm that is associated with a poor prognosis. PMID- 7991213 TI - Acrylamide-induced distal axon degeneration: a proposed mechanism of action. AB - Exposure to acrylamide (ACR) monomer produces distal swelling and subsequent degeneration in central and peripheral myelinated axons of humans and laboratory animals. The molecular and cellular events leading to this type of axonopathy are currently unknown. Herein we describe a new mechanism of ACR axonopathy that represents a synthesis of recent research findings and prior hypotheses. According to this model, ion regulation in distal paranodal axon regions is compromised by diminished axolemmal Na/K-ATPase activity. It is suggested that decreased NA/K-ATPase activity is a consequence of aberrant cell body processing and/or deficient axonal transport. Reduced Na pump activity promotes membrane depolarization in conjunction with axoplasmic accumulation of Na and loss of K. Thermodynamically, this favors reverse operation of the Na/Ca-exchanger which permits axonal Ca entry in exchange for Na. The influx of Ca eventually overwhelms buffering mechanisms and leads to distal axon degeneration. Distal axons are predisposed to regulatory failure of this type due to a dependency on cell body output and the unique differential distribution of enzymes, ion channels and exchangers among nodal and internodal regions. This heuristic model might account for axon degeneration occurring as a result of exposure to other chemical neurotoxicants and following axotomy and other forms of mechanical injury. PMID- 7991214 TI - p,p'-DDT myoclonic/epileptic model: serotonin receptor binding and behavioral studies in the rat. AB - An abnormality of serotonergic neurotransmission has been hypothesized in p,p' DDT intoxication to explain myoclonus and the antimyoclonic properties of 5 hydroxytryptophan (5-HTP). To study the role of serotonin (5-HT) receptors in myoclonus induced by p,p'-DDT in the rat, we performed time-course and dose response studies of the effects of p,p'-DDT on behavior and regional 5-HT1 and 5 HT2 binding sites. At a time when low dose (80 mg/kg) p,p'-DDT elicited stimulus sensitive and spontaneous myoclonus, there were no significant changes in Bmax or Kd of 5-HT1A, 5-HT1B, 5-HT1C sites in cortex, striatum, brainstem or spinal cord, agonist- or antagonist-labelled 5-HT2 sites in cortex, or 5-HT uptake sites. High dose p,p'-DDT (1000 but not 500 mg/kg), which also induced convulsions, only slightly increased 5-HT1 (unsubtyped) binding sites in cortex but not in brainstem or spinal cord and had no effect on antagonist-labelled 5-HT2 sites. In naive frontal cortex in vitro, 1 microM p,p'-DDT displaced neither [3H]5-HT or [3H]ketanserin specific binding. Lesions of central indoleamine neurons made with 5,7-dihydroxytryptamine significantly prolonged the latency and attenuated the severity of p,p'-DDT behavioral abnormalities, increasing the dose of p,p'-DDT which induced myoclonus (MD50) or convulsions (CD50) in 50 percent of the rats. This is the first report of 5,7-DHT-induced attenuation in the p,p'-DDT myoclonic model. PMID- 7991215 TI - Ultrasound-induced epileptiform activity in rats treated with hexachlorobenzene. AB - Hexachlorobenzene (HCB), an environmental contaminant, has caused spontaneous convulsions in infants and neonate rats born and breast-fed from exposed mothers as well as in weanling rats exposed for many weeks. This study aimed to determine if HCB causes epileptiform convulsions in adult rats. For this purpose, a controlled stimulus was used. Female Sprague-Dawley rats received HCB (100 mg/kg in corn oil) by daily gavage; on days 7 to 13, rats were exposed to a short ultrasound stimulation 24 hr after each administration. Ultrasound-induced epileptiform activity characterized by a burst of erratic running and leaping and tonic-clonic convulsions was observed in 0, 0, 10, 40, 90, 90 and 100% of rats having received a cumulative dose of 600, 700, 800, 900, 1000, 1100 and 1200 mg/kg, respectively. A similar dose-response pattern was obtained for tremors observed in HCB-treated rats. For a 800 mg/kg group left without further treatment, a three-fold increase in the percentage of rats with epileptiform activity was observed two days after the end of treatment. In summary, ultrasound stimulation has permitted us to demonstrate in a reproducible manner that adult rats treated with HCB display epileptiform activity. PMID- 7991216 TI - Dimethylhexanedione impairs the movement of neurofilament protein subunits, NFM and NFL, in the optic system. AB - Exposure to the neurotoxic gamma-diketone 3,4-dimethyl-2,5-hexanedione (DMHD) leads to the accumulation of neurofilaments within the proximal axon and to an inhibition in the rate of anterograde transport of recently synthesized neurofilaments. These effects of DMHD are similar to those of the neurotoxic nitrile 3,3'-iminodipropionitrile (IDPN), which is also characterized by formation of neurofilamentous swellings within the proximal axon and an inhibition of transport, both of newly synthesized neurofilaments and those already in transit in more distal regions of the axon. Due to the similarities between these compounds, DMHD also might be expected to inhibit neurofilament transport in the distal axon. The objective of this study was to examine the effects of DMHD on the movement of labeled neurofilament proteins which were in transit at the time of intoxication. Proteins in the optic system, pulse labeled with 35S-methionine, underwent transport for two weeks prior to the start of intoxication. Neurofilament transport was assessed by SDS-PAGE fluorography and computerized densitometry. At two and five weeks in control animals, the peaks of NFL and NFM neurofilament subunits had broadened and flattened from their original proximal location and assumed a more uniform, proximodistal distribution (peak dispersion). In contrast, in DMHD-treated animals, the radiolabeled NFL and NFM remained near their position at the start of intoxication, retaining a peak of radiolabeled protein. A proportion of each of the subunits, however, had entered the distal axon during intoxication suggesting that a population of filaments may remain transport competent.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7991217 TI - Olfactory toxicity resulting from dermal application of 2,6-dichlorobenzonitrile (dichlobenil) in the C57Bl mouse. AB - 2,6-Dichlorobenzonitrile (dichlobenil) is an herbicide which has previously been reported by other investigators to be toxic to the olfactory mucosa following intraperitoneal administration. The objective of this study was to determine whether a more occupationally-relevant route of pesticide exposure, namely dermal exposure to dichlobenil, also resulted in olfactory system damage. Male C57Bl mice were clipped and administered 0-200 mg/kg dichlobenil dermally in acetone either as a single dose or for five consecutive days. In addition, olfactory bulb glial fibrillary acidic protein (GFAP) analysis was performed in order to determine whether the damage in the olfactory mucosa translated into damage which could be measured as an astroglial increase in GFAP concentration in the olfactory bulb, a marker of central nervous system neuronal loss. Olfactory mucosal histology revealed that single or multiple exposures to 50, 100, 150 and 200 mg/kg dichlobenil dermally caused olfactory epithelial damage (primarily sensory cell loss) in the epithelium lining the dorsal medial meatus of the nasal cavity. While the olfactory epithelial lesions were much less severe than those caused by i.p. administration of dichlobenil, GFAP was significantly elevated in both the 150 and 200 mg/kg treatment groups, demonstrating that relatively minor damage to a portion of the olfactory mucosa in the nasal cavity can be detected in the central nervous system. PMID- 7991218 TI - Homogeneity of regional brain lead concentrations. AB - It has been proposed that the neurobiological basis of many of the behavioral manifestations arising in response to Pb exposure may be due to selective vulnerability of particular brain regions, such as hippocampus, a region in which preferential accumulation has been reported in some studies. However, these findings have not been invariant and, in fact, have been found to vary with dosing parameters. This study examined potential regional accumulation of Pb in brain following postnatal exposure of rats to Pb via nursing dams consuming Pb acetate solutions of 0, 100, 350, 1000, or 2000 ppm. Offspring were sacrificed at 7, 14, 21, 40 or 60 days of age and brains dissected into 12 regions, including striatum, nucleus accumbens, hypothalamus, thalamus, ventral (tegmentum) and dorsal (tectum) midbrain, hippocampus, frontal, parietal/temporal, and occipital cortices, cerebellum and brain stem for regional Pb analyses. All brain regions generally accumulated Pb in a similar pattern. Regional elimination half-lives, determined for the 350, 1000 and 2000 ppm exposure groups, averaged about 20 days and did not vary between regions. Regional brain Pb levels were not different whether brains were perfused or not prior to brain Pb determinations. However, regional differences in brain Pb levels could be introduced by using dry, rather than wet weights in the calculation of Pb concentrations, and by procedures including soaking in formaldehyde prior to drying, probably as a result of the differential fluid volume of different brain regions. Taken together, these data do not support previous findings of selective regional accumulation of Pb in any brain region, including the hippocampus, at least under conditions of postnatal Pb exposure and wet weight measures. While there may indeed be differences among brain regions in sensitivity to Pb, any differences in response among brain regions should probably be ascribed to differences in the interactions of Pb with biochemical or cellular targets unique or enriched in that region rather than to differences in accumulation of Pb. PMID- 7991219 TI - Neuropathy target esterase inhibition by organophosphorus esters in human neuroblastoma cells. AB - Certain organophosphorus compounds (OPs) produce a delayed neuropathy (OPIDN) in man and some animal species. Capability to cause OPIDN is generally predicted in animal models by early and irreversible inhibition of neuropathy target esterase (NTE, neurotoxic esterase). In this study, NTE inhibition in response to OP exposure was examined in cell culture, using the human SH-SY5Y neuroblastoma cell line. Cells were exposed for 1 hr to equimolar (1 x 10(-5) M) concentrations of 6 OPs associated with OPIDN in vivo (including 2 protoxicants and 4 active (-P = O) toxicants), and 8 OPs that do not produce delayed neuropathy in animal models (including 5 protoxicants and 3 -P = O compounds). The -P = O compounds that cause OPIDN in animal models inhibited NTE > 60% at the test concentration; -P = O compounds that do not cause OPIDN in animal models inhibited NTE < 30%. Protoxicants did not inhibit NTE at the test concentration, reflecting their limited metabolism in the human cell line. These results indicate that human neuroblastoma cells have potential use in the initial screening of bioactive OPs with capability for causing OPIDN. PMID- 7991220 TI - Spinal cord uptake of lead injected into muscle. AB - It has been hypothesised that some motor neuron diseases may result from lead (Pb) being retrogradely transported in axons from muscle to spinal cord. To test this hypothesis, we injected mice in the right hindlimb with 0.1 ml of 0.25% or 2.5% Pb. In some animals the sciatic nerve was cut before injection. Pb levels were measured in the lumbar and thoracic spinal cord and the kidney with atomic absorption spectrophotometry (AAS). Four weeks after injection, Pb was found in the spinal cord on AAS, with higher levels in the lumbar than the thoracic cord only in the high-Pb group. Sciatic nerve cut did not inhibit the passage of Pb to the cord. The results suggest that most Pb injected into muscle reaches the spinal cord via the blood or damaged axons, rather than via intact axons. These data do not support the hypothesis of Pb-induced motor neuron disease via retrograde axonal transport from muscle. PMID- 7991221 TI - Energy related metabolic alterations in diaphragm muscle resulting from acute methomyl toxicity. AB - Male Sprague-Dawley rats receiving an acute dose of methomyl (5 mg/Kg, sc) developed overt signs of toxicity within 2 min. The maximum severity, including muscle fasciculations and convulsions, was attained within 7-10 min and lasted for about 30 min. A very rapid recovery followed and by 90 min rats were free from obvious toxicity. During intoxication, the body temperature was significantly below normal. In diaphragm, when the activity of acetylcholinesterase (AChE) was markedly depressed (82%), the levels of high energy phosphates, adenosine triphosphate (ATP) and phosphocreatine (PCr) were also significantly lowered (27% and 54%, respectively). Significant decreases in the levels of adenosine diphosphate (ADP, 19%), total adenine nucleotides (TAN, 27%), creatine (Cr, 27%), and total creatine compounds (TCrC, 29%) were noted at various intervals. The ratio of PCr/Cr was reduced by 53%. The adenylate energy charge [(ATP + 1/2 ADP)/(ATP + ADP + AMP)], an indicator of high-energy phosphate bond availability, remained unchanged throughout the time course. More than twofold elevation in the activity of Mg(2+)-facilitated creatine kinase (reverse Lohmann reaction) in diaphragm (CK-MM) and more than twofold increase in the levels of glucose in serum, were suggestive of greater synthesis of ATP. Higher activity of CK-MM was also noted in the serum. That high-energy phosphates were partially depleted suggested that the rate of ATP utilization was far greater than its synthesis. Methomyl intoxication also resulted in higher activity of LDH and its isoenzymes in muscle as a result of induced greater synthesis. Elevation of CK and LDH and their isoenzymes in the serum was probably a result of their leakage from the tissues due to loss of membrane permeability caused by significant depletion of ATP and PCr. PMID- 7991222 TI - Electromyography in relation to end-plate acetylcholinesterase in rats poisoned by different organophosphates. AB - Organophosphate (OP) poisoning produces various forms of acute, subacute, or delayed neurotoxicity. We investigated in vivo the relationship between clinical, histochemical and electromyographic (EMG) parameters in rats at various stages of poisoning by paraoxon or fenthion. Paraoxon is acutely toxic, whereas fenthion produces more sustained AChE inhibition. Fenthion has been involved in a subacute type of OP-related neurotoxicity in patients, the so-called intermediate syndrome. The animals underwent serial EMGs, with single and repetitive nerve stimulation, and concomitant contralateral muscle biopsies to determine the end plate acetylcholinesterase (AChE) activity. Repetitive activity (RA) after single nerve stimulation and decrements on repetitive nerve stimulation (RNS) were the major EMG findings in either type of poisoning, occurring in the initial and later stages of the poisoning, respectively. RA was highly correlated to fasciculations in acute, but not in prolonged intoxication. Amplitude decrements provoked by RNS occurred only in weak rats with severe end-plate AChE inhibition. The smallest amplitude occurred either at the second response with gradual improvement in the subsequent responses (decrement-increment phenomenon), or the amplitude decrease progressed up to the last response (decrement phenomenon). The decrement-increment phenomenon preceded the decrement phenomenon and occurred at a slightly less severe degree of AChE inhibition. Various types of impairment of neuromuscular transmission coexist, probably to a different extent at distinct stages of anticholinesterase poisoning. PMID- 7991223 TI - Acute and subacute organophosphate poisoning in the rat. AB - The intermediate syndrome in organophosphate poisoning is clinically characterized by weakness in the territory of cranial nerves, weakness of respiratory, neck and proximal limb muscles, and depressed deep tendon reflexes. It occurs between the acute cholinergic crisis and the usual onset of organophosphate-induced delayed neurotoxicity. The weakness has been ascribed to muscle fiber necrosis. Fenthion has been the most common cause. This study assesses the occurrence of the necrotizing myopathy in rats in relation to the clinical course and the acetylcholinesterase (AChE) inhibition after poisoning with organophosphates representative for each of the major types of organophosphate-related neurotoxicity. Marked differences are noted in the duration of cholinergic symptoms and of AChE inhibition after either paraoxon and mipafox, or fenthion poisoning. The necrotizing myopathy begins shortly after the initial decline in AChE activity with all organophosphates studied. Maximal muscle involvement occurs within the first 2 days of the poisoning with all organophosphates studied. The myopathy is not aggravated by a further decline in AChE activity in fenthion poisoning. Our data argues against the monophasic necrotizing myopathy being the cause of the intermediate syndrome, and is suggestive of persistent AChE inhibition being involved. PMID- 7991224 TI - The use of an unbaited tunnel maze in neurotoxicology: I. Trimethyltin-induced brain lesions. AB - In our laboratory we use an unbaited 6-arm radial tunnel maze (6-arm RTM) to assess working and reference memory in the course of neurotoxicity studies. The 6 arm RTM is believed to measure parameters comparable to those assessed in radial arm mazes, but without the need of food deprivation and rewarding of animals. This is especially useful in the course of neurotoxicity studies as interferences of e.g. food deprivation with drug pharmacokinetics can be avoided. Since the 6 arm RTM is less evaluated than conventional mazes the aim of this study was to further confirm mean error score as measure of 'working memory', left-right discrimination within each radial arm (expressed as percent "blind-alley" visits) as measure of 'reference memory', and number of arm entries/min as a measure of motor activity. Therefore, hippocampal lesions were induced by injecting animals with the neurotoxicant trimethyltin (TMT). TMT at a dose of 5 mg/kg slightly lesioned hippocampal CA3 pyramidal cells in 3 of 8 animals, but did not affect behavioral measures in the 6-arm RTM. In all surviving animals treated with 7 or 9 mg/kg TMT moderate to marked loss of CA3 pyramidal cells was observed, while in 4 of these 7 rats CA4 pyramidal cells were also affected. Other brain lesions were not observed. TMT-induced brain lesions led to increased mean error score and number of arm visits during the retention phase and after changing maze configuration, whereas percent "blind-alley" visits were not affected.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7991225 TI - The use of an unbaited radial maze in neurotoxicology: II. Sensory inputs, general malaise and locomotor activity. AB - An unbaited 6-arm radial tunnel maze (6-arm RTM) is used in our laboratory to screen for working- and reference memory deficits in rats in the course of neurotoxicological studies. In the 6-arm RTM animals are minimally stressed, and do not need food reward as a reinforcer. Maze behavior is assessed using mean error score of arm repetitions as a measure of 'working memory', left-right discrimination within each arm (expressed as percent "blind-alley" visits) as a measure of 'reference memory' and trial time (time to complete 12 arm entries) as a measure of locomotor activity. As shown for other mazes sensory deficits may affect spatial orientation. Sensory dysfunction are likely to be induced by neurotoxic compounds, while at toxic doses reduced locomotor activity is a common finding. When using the 6-arm RTM in the course of neurotoxicity studies to assess cognitive functions such potentially confounding effects have to be excluded to allow the conclusion of a cognitive impairment. The aim of the following experiments was to assess if visual, vibrissal or olfactory dysfunction, or hypoactivity may affect memory parameters in the 6-arm RTM. Loss of visual, olfactory or vibrissal input alone did not affect any of the maze parameters. Combined loss of visual and vibrissal or olfactory inputs increased mean error score. Loss of olfaction prolonged trial time under both lighting conditions. Acrylamide- and vitamin B6-induced sensorymotor dysfunctions and hypoactivity did not affect mean error score or percent blind-alley visits in the 6-arm RTM. Similarly, gastrointestinal distress and hypoactivity induced by lithium chloride injections did not affect parameters of working or reference memory. Results indicate that in the 6-arm RTM (1) olfactory, visual and, to a minor extent, vibrissal input contribute to the sensory information necessary for spatial orientation and (2) reduced locomotor activity secondary to impaired sensorymotor abilities or drug-induced illness do not influence working or reference memory parameter. PMID- 7991226 TI - Pharmacokinetics and distribution of tris(maltolato)aluminum(III) into the central nervous system. AB - The maltolate compound of aluminum (Al), tris(maltolato)aluminum(III), has been demonstrated to be quite toxic after central administration and in cell cultures. However, reports of peripheral Al-maltolate administration in vivo demonstrated unimpressive neurological effects. We found no reports of Al-maltolate pharmacokinetics or its distribution into the central nervous system (CNS) after systemic administration. In the present study, we evaluated Al pharmacokinetics in serum and Al distribution into brain extracellular fluid (ECF) in rats following Al-maltolate administration. The pharmacokinetic studies revealed that systemic clearance, elimination half-life and mean residence time were 42 (+/- 5) ml/hr/kg, 2.2 (+/- 0.5) hr and 3.1 (+/- 0.7) hr [mean +/- SD), respectively. The steady state volume of distribution (Vss) for Al-maltolate was 130 ml/kg. This Vss suggests that Al-maltolate may exhibit limited distribution outside the vascular compartment, which is estimated to be approximately 80 ml/kg in these rats. Previously, we used microdialysis (MD) probes to assess Al-citrate distribution into the CNS. MD was utilized in the present study to evaluate the CNS distribution of Al as a result of Al-maltolate administration. MD probes were implanted into the frontal cortex (FC) and jugular vein to sample Al from brain and blood ECF, respectively. Al was not measurable in FC MD probe dialysates after a 0.5 mmol/kg Al (as maltolate) bolus, but could be measured after steady state blood and brain ECF Al concentrations had been achieved. The Al brain/blood ration calculated from Al-maltolate steady state brain and blood MD samples was 0.04, significantly less than those calculated for other Al salts at equimolar Al doses.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7991227 TI - Studies on the neuromuscular blocking action of commercial paraquat in mouse phrenic nerve-diaphragm. AB - The neuromuscular blocking actions of commercial and pure paraquat on the mouse phrenic nerve-diaphragm were compared. Twitch responses of mouse diaphragm to nerve stimulation were inhibited by commercial paraquat (5-500 microM), but not by pure paraquat (1 mM). At concentrations greater than 30 microM, commercial paraquat also directly inhibited the contractions induced by electrical stimulation of the muscle. The inhibitory actions of commercial paraquat on twitches were potentiated by pretreatment with either 0.7 microM d-tubocurarine or 2.2 microM succinylcholine. Moreover, commercial paraquat inhibited acetylcholine contracture of the denervated mouse diaphragm. Similar to d tubocurarine, commercial paraquat protected the diaphragms from inhibition by alpha-bungarotoxin and also inhibit the binding [125I]-alpha-bungarotoxin. Electrophysiological studies revealed that commercial paraquat inhibited the amplitude of miniature end-plate potentials (m.e.p.ps) and end-plate potentials (e.p.ps) of mouse diaphragm. The inhibition induced by commercial paraquat was frequency-dependent. All of these findings indicate that commercial paraquat possesses curare-like actions and inhibits muscle contractions by binding to the postsynaptic nicotinic acetylcholine receptors. Pure paraquat does not have these effects. Analysis of the components in commercial paraquat suggested that paraquat by-products and the added emulsifying agent were responsible for these observations. The clinical significance of these findings is that this neuromuscular blocking may contribute to the respiratory failure in paraquat intoxicated patients. PMID- 7991228 TI - Chronic lead exposure induces astrogliosis in hippocampus and cerebellum. AB - The aim of this study was to characterize the cytoskeletal intermediate filaments, glial fibrillary acidic protein (GFAP), and vimentin in normal and lead treated rats, and to compare the astroglial response in the cerebellum and the hippocampus -two regions with great susceptibility to the toxic effects of lead. Experiments combined light and electron microscopy immunohistochemistry using antibodies to GFAP and to vimentin, and conventional transmission electron microscopy techniques. Chronic lead administration was provided through the drinking water (1 g% lead acetate solution) and started when pups were 7 days old through the mother's milk. Following weaning lead intoxicated offspring were continuously exposed during 9 months, and sacrificed, with their corresponding controls, by perfusion-fixation at 30, 60, 75, 90, 180 and 270 days of lead exposure. After 60 and 90 days of treatment, hypertrophic astrocytes were observed in the cerebellum and hippocampus. Additionally, in the same time-period more GFAP immunolabelled astrocytes were detected in the cerebellum but not in the hippocampus. These qualitative observations were confirmed by computerized image analysis quantification. This effect was transient, even though the lead treatment was prolonged for 9 months and the blood-lead levels remained high after 30 days of the lead-exposure. After 90 days of lead administration, hypertrophic astrocytes started to decline and a gradual increment in the number of dense bodies, lipofuscin-like, was evidenced in astrocytes, neurons, pericytes and microglial cells. The data suggest that chronic lead exposure induces an astrocytic reaction as a result of a direct action of lead on astroglial cells or as a response to underlying neural damage. PMID- 7991229 TI - Comparative effects of inorganic divalent mercury, methylmercury and phenylmercury on membrane excitability and synaptic transmission of CA1 neurons in hippocampal slices of the rat. AB - Comparative effects of inorganic mercury (Hg2+), methylmercury (MeHg) and phenylmercuric acetate (PMA) on central synaptic transmission were examined by recording field potentials from CA1 neurons of rat hippocampal slices before and after acute bath application of mercurials at 20 and 100 microM. At 100 microM, Hg2+ decreased the amplitude of population spikes (PSs) to complete block; average time to block was 25 +/- 4 min. Application of 20 microM Hg2+ for 120 min gradually decreased PS amplitude to 33% of control. Effects of Hg2+ on excitatory postsynaptic potentials (EPSPs) were comparatively slow. Application of 100 microM Hg2+ for 120 min only reduced EPSP amplitude to 60% of control; no complete block occurred, suggesting an effect primarily on the postsynaptic CA1 cell membrane. In contrast to Hg2+, MeHg at 20 and 100 microM first increased amplitudes of PSs and EPSPs significantly and then decreased both to complete block. Average times to block of PSs and EPSPs by 100 microM MeHg were 41 +/- 4 and 42 +/- 4 min, respectively. PMA caused similar effects on PSs and EPSPs as did MeHg. However, unlike MeHg, the increased amplitudes of PSs and EPSPs by PMA were not statistically significant. At 20 microM, PMA appeared to be more effective at blocking PSs and EPSPs than were Hg2+ and MeHg. Washing slices with artificial cerebrospinal fluid containing 1 mM D-penicillamine completely reversed the effects of Hg2+ on PSs and EPSPs and effects of MeHg on EPSPs in 90 min, but only partially reversed the effects of MeHg on PSs. D-penicillamine could reverse neither the effects of PMA on PSs nor EPSPs. It is concluded that these perturbations produced damage to the associated physiological functions leading to CNS dysfunctions. PMID- 7991230 TI - Microchromatographic analysis of lipids, protein, and occurrence of lipid peroxidation in various brain areas of vanadium exposed rats: a possible mechanism of vanadium neurotoxicity. AB - Administration of sodium metavanadate (3 mg/kg) to adult female Sprague Dawley rats for 5 consecutive days by intraperitoneal route resulted in major alterations in lipid profiles and protein concentration in all the brain regions. Sodium metavanadate exposure displayed significant decrease in the levels of total lipids, phospholipids, cholesterol and cerebrosides, and protein, but ganglioside concentration was significantly increased in various areas of the brain. Loss of body weight observed in this study could be attributed to the loss of appetite; loss of nutrients and wasting of tissues. It is likely that large amount of body water was lost through diarrhoea. Gas liquid chromatography has revealed that oleic acid, linoleic acid, linolenic acid, and arachidonic acid were preferentially lost in the brain of vanadium-exposed rats. Thin layer chromatography further proved degradation of individual lipids. Sphingomyelin was substantially decreased followed by phosphatidyl choline and phosphatidyl ethanolamine, but phosphatidyl serine and phosphatidyl inositol were slightly affected. Our recent work has demonstrated vanadium-induced stimulation of lipid peroxidation in the various regions of the rat brain. It is speculative that deterioration of myelin sheath by vanadium exposure contributed to preferential lipid loss but lesser loss of protein. These studies also indicate that vanadium induced stimulation of lipid peroxidation is characterized by a selective loss of brain polyunsaturated fatty acids and thus comprehensive degradation of lipids in the different regions of the rat brain. However, the mechanism involved in the elevation of ganglioside levels is not yet fully understood. It is concluded that these perturbations produced damage to the associated physiological functions leading to CNS functions. PMID- 7991231 TI - Subspecialization in obstetrics and gynecology: pros and cons. PMID- 7991232 TI - Incarceration of the gravid uterus. AB - Retroversion of the first trimester uterus occurs in 6 to 19 per cent of all pregnancies and usually does not cause problems. If the uterus remains retroverted as the pregnancy advances, it may become wedged into the pelvic cavity. This complication is referred to as uterine incarceration which can lead to spontaneous abortion, preterm labor, uterine dystocia, and inadvertent incision into the cervix or the bladder during cesarean section in cases of unrecognized incarceration. Seven cases of uterine incarceration are presented with a detailed review including clinical signs and symptoms, physical findings, ultrasound findings, and treatment modalities for each stage of pregnancy. Moreover, we present a new method of treatment for second trimester uterine incarceration. PMID- 7991233 TI - Sonographic characteristics of antenatally diagnosed extralobar pulmonary sequestration and congenital cystic adenomatoid malformation. AB - Fetal chest masses are uncommonly noted on obstetrical ultrasound examinations. Some masses will undergo in utero regression with no neonatal morbidity whereas others are almost universally fatal. An accurate prenatal diagnosis is essential in enhancing parental decision-making. This paper reviews the published literature of two specific kinds of prenatally diagnosed fetal chest masses (congenital cystic adenomatoid malformations and pulmonary sequestrations) with emphasis on ultrasound characteristics and pregnancy outcome. PMID- 7991234 TI - Prenatal ultrasound diagnosis of conjoined twins. AB - Four cases of conjoined twins are presented. On the basis of these cases and a review of the literature we present the ultrasonographic features to diagnose this rare condition prenatally in its various forms. Recommendations to avoid misdiagnosis are given. Consequences of this diagnosis and assessment of shared organs are discussed for counselling and obstetrical care. PMID- 7991235 TI - [The forms of variability in a cell population as well as in an organism population. The biology of the development of the cardiac myocytes]. AB - Variability of cells is analyzed using data obtained in studies on polyploidy in the heart muscle and on ontogenetic changes in the number of myocytes. In normal myocardium, variation in the number and ploidy of muscle cells is observed. The types of genomic variation are similar to those found in populations of organisms, i. e., to hereditary and modifying variation. In studies on modifications of the myocyte genome, heart growth reserves were revealed, which manifest themselves in pathological states associated with myocardial hypertrophy. These reserves depend on the level of myocardial polyploidy that is determined during early postnatal development. PMID- 7991236 TI - A hypothesis: reciprocal information transfer between oligoribonucleotides and oligopeptides in prebiotic molecular evolution. AB - We wish to propose a mechanism for reciprocal information transfer in prebiotic molecular evolution, based on heterologous pairing complex formation between oligoribonucleotides and oligopeptides. In this proposed pairing complex, the bases of the oligoribonucleotide and the side chains of the oligopeptide may form three types of complementary Watson-Crick-type hydrogen bonds. The structural basis for the pairing is the close correspondence of the distances between the side chains in the two molecules. Both the inter-nucleotide spacing of the RNA and the inter-side-chain spacing of the peptide are approximately 3.4 A. The proposed pairing mode would allow both specific and nonspecific interactions required for reciprocal information transfer. Thus, it represents a simple and versatile coding system that could have had significant implications in prebiotic molecular selection and evolution. In addition, we propose several testable experimental approaches based on the pairing mode of oligoribonucleotides and oligopeptides to verify our hypothesis. PMID- 7991237 TI - [Comparative analysis of ultrasonic studies, histopathological data and clinical parameters in dysfunctioning renal transplantation]. AB - The correlation of B mode and Doppler sonographic parameters and diagnoses established by histological examination of graft biopsies, nephrectomies and clinical data are discussed. 48 histological samples from 36 patients were reevaluated. The maximum interval between sonography and histology was 36 hours. The Banff classification criteria were used during histological examinations. Doppler examination evaluation was based on the resistance index (RI). Reproducibility was controlled by means of intra- and interobserver variability in 10 patients. RI values higher than 75% were regarded as abnormal. On the basis of these observations and the literature data specific sonographic features can be detected in renal artery occlusion and renal vein thrombosis. In pyelonephritis, dilatation of the collecting system was frequent. No morphological changes were detected in cyclosporin-A nephrotoxicity and the Doppler signs were not characteristic for this disease. No differentiation was found between acute rejection and acute tubular necrosis. The noninvasive duplex sonographic examinations can provide very important information regarding the flow situation of a transplanted kidney. In some cases a definitive diagnosis can be achieved, but in other cases biopsy is the method of choice. PMID- 7991238 TI - [Clinical significance of the ultrasensitive TSH assay]. AB - The authors attempted to answer the question whether the low thyroid stimulating hormone (TSH) levels measurable by the TSH ultrasensitive DELFIA kit have any clinical significance and whether they are more informative than the results obtained by the supersensitive TSH assay. No measurable TSH was detected in 111 sera among 896 random specimens, by using a supersensitive fluorimetric kit. These 111 sera were further investigated, TSH was measured by an ultrasensitive assay, in addition, the levels of the peripheral hormones (total T4, total T3, T3 uptake, free T4, free T3), were also determined. On basis of the latter, the patients were classified as having subclinical (n = 28) or manifest (n = 80) hyperthyroidism. The TSH levels of the patients affected by manifest hyperthyroidism were found significantly (p < 0.0001) lower than those encountered in subclinical hyperthyroidism. The groups were then further divided to homogeneous clinical subgroups (patients treated with thyrostatic drugs, untreated patients, toxic adenoma, Graves' disease) and the results were analyzed. It can be stated that the ultrasensitive test safely distinguishes manifest and subclinical disease in all subgroups (range of sensitivity: 90.0 94.7%). Specificity for the diagnosis of subclinical hyperthyroidism was 66.7% for the untreated subgroups, irrespective of aetiology, while in treated patients the value of specificity was 10%. In Graves' disease, specificity was 100%, in toxic adenoma 0% (the number of patients, however, was very small in these homogeneous subgroups). These results suggest that although the ultrasensitive method furnishes more information than the supersensitive test, its exclusive application would not be appropriate in characterizing thyroid function because of the broad range of individual scatter. PMID- 7991239 TI - [Treatment of methimazole-induced agranulocytosis with granulocyte-macrophage colony stimulating factor]. AB - The authors treated a patient with methimazol (Metothyrin)-induced agranulocytosis with human recombinant granulocyte-macrophage colony stimulating factor (GM-CSF). On day seven, after combined antibiotics, corticosteroid and at a dose of 270 ug daily subcutaneous GM-CSF therapy the septic state of the patients rapidly cured and the leucocytes reached the peripheric blood. No side effects were found. The publication of this case history might help to determine the place of human GM-CSF-s therapy in the treatment of agranulocytosis of different origin. PMID- 7991240 TI - [Paracetamol poisoning in infancy--is paracetamol safe?]. AB - A 5-month-old baby was observed. At the severely ill infant accidental misadministration of Paracetamol was verified. After surveying the literature the authors discussed the possible pathobiochemical ways and draw attention to the dangers of the misuse of antipyretics. PMID- 7991242 TI - [Clinical spectrum of distal renal tubular acidosis and its study with bicarbonate loading]. AB - Authors attempted to review the clinical spectrum of distal renal tubular acidosis on the basis of analysing the records of 11 patients. Distal renal tubular acidosis was associated with chronic renal failure of different severity and with tubulointerstitial diseases in the two-third of patients in whom histologic studies were also performed. The disorders caused in certain cases hypokalemia and hyperkalemia in the others, the concentrating insufficiency was characteristic leading in exceptional cases to nephrogenic diabetes insipidus and the clinical picture was accompanied also by osteomalacia. Authors describe their own method of bicarbonate loading, obtaining by its use very high values of 78.65 +/- 11.28 (p < 0.005) mmHg of urine minus blood pCO2 in 6 healthy subjects. On the other hand, in 6 distal renal tubular acidosis patients no such difference in the pCO2 values could be found. The knowledge of the clinical spectrum of the distal renal tubular acidosis may enhance the recognition and treatment of the disorder. PMID- 7991241 TI - [Direct dissolution therapy of biliary tract calculi]. AB - The aim of this study was to evaluate the effect of a recently developed biphasic multicomponent solvent in 39 patients with biliary duct stones that are too large (15-35 mm) to be removed after endoscopic sphincterotomy. From November 1991 to October 1993, 37 patients with common bile duct stones were papillotomized during endoscopic retrograde cholangiography and a nasobiliary catheter was positioned above the stone. In 2 patients, the residual stones were dissolved via the T-tube inserted during cholecystectomy. Solvent mixtures (solvent 1:26 mM ethylene diamine tetraacetic acid, 40 mM sodium deoxycholate and 30% dimethyl sulfoxide in an aqueous buffer solution glycine-NaOH, pH: 9.2; solvent 2: a 70: 30 mixture of dimethyl sulfoxide and methyl-tert-butyl-ether) were infused continuously and alternatively for 2 h at a rate of 0.3-0.5 ml/kg b.w./h. In order to diminish the absorption of the solvent from the duodenum, charcoal was given orally periodically. Fluoroscopy indicated that the common bile duct stones disappeared during 13-24 h of infusion in 10 of 39 patients. In 25 patients, the size of the stones diminished sufficiently for them to be removed by basket extraction. In 4 patients, the size of the stone did not change and surgery (1 pt) or endoscopic stenting (3 pts) was required. Only mild toxic side-effects were observed, including laboratory abnormalities and moderate duodenitis (34/39). Transient abdominal pain and/or cramp (21/39), nausea and vomiting (34/39) and diarrhoea (19/39) were the most common complaints during treatment.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7991243 TI - [Relationship between urticaria-like toxic allergic exanthema and infection by toxin-producing Staphylococcus strains in infants]. AB - The author observed that in the throat and/or nasal culture of approximately 80% of little children admitted to hospital with urticaria-like toxic-allergic exanthem, exotoxin-producing strains of Staphylococcus aureus could be isolated. In 15 of the 19 cases presented. Toxic Shock Syndrome Toxin (TSST-1) and in 4 cases various enterotoxins were identified. With aimed antibiotic treatment the skin symptoms of the children healed up in 3-4 days. Thus, the following question is raised: when facing the Toxic Shock Syndrome Toxin for the first time, why do children develop only skin symptoms, without severe complications of the Toxic Shock Syndrome observed in adult patients. It is assumed that similarly to classic infectious diseases, the course of the illness is milder in little childhood and the frequency of complications are lower than in adulthood. This phenomenon may be attributed to the immature immune reactivity of little children. PMID- 7991244 TI - ["Loop"-drainage in the management of recurrent extra-sphincteric perianal fistulae]. AB - This work covers the loop seton drainage tube treatment of multiply recurring high-spreading extrasphincteric perianal fistulas in 14 patients. The drainage loop setons make possible the rinsing of the wound after fistulectomy and bi directional drainage of the wound discharge. Strangulation of the wound, and hence the development of recurrence, is prevented by means of controlled formation of scar tissue. The sphincteral musculature of the anus is protected from damage. 25 fistulas which recurred in the 14 patients were treated successfully by this method. None of the patients developed incontinence. 1 fistula recurred. With regard to the pull-out method, in the case of high spreading multiply recurring extrasphincteric or suprasphincteric perianal fistulas. PMID- 7991245 TI - [Thyroid-stimulating hormone-secreting pituitary adenoma]. AB - A 40-year-old male patient with a 2 years history of recurring hyperthyroidism is presented with clinical hyperthyroidism and diffuse goiter. Despite thyreostatic treatment and surgical thyroid ablation the hyperthyroidism recurred. The patient had laboratory evidence of hyperthyroidism and his serum TSH was persistently and enormously elevated (T4:214 nmol/l, T3:6.9 nmol/l, TSH:218 mIU/l)> Computed tomography and magnetic resonance imaging confirmed a pituitary mass of 7 cm in a p diameter, with supra-, parasellar and sphenoidal extension. The pituitary adenoma was partially resected by transsphenoidal surgery, which failed to result in a substantial decrease in the serum thyrotropin level. Pituitary irradiation and a long-term somatostatin analog octreotide treatment (300-600 micrograms/die) combined with bromocriptine therapy resulted in a significant, but still incomplete suppression of thyrotropin secretion (TSH level about 15 mIU/l) and persisting mild hyperthyroidism. The size of the adenoma was unchanged during the two years of highdose octreotide treatment period. According to our best knowledge this is the first reported case of a thyrotropin-secreting pituitary adenoma in Hungary. PMID- 7991246 TI - Historical biography: George Kelemen. PMID- 7991247 TI - Hearing preservation in acoustic neuroma surgery: value of monitoring cochlear nerve action potentials. AB - This study reviews the hearing results in 80 consecutive patients who underwent complete removal of histologically proven acoustic neuromas by use of the suboccipital approach. Of these, 56 patients had successful monitoring of cochlear compound action potentials; 20 were not monitored because their surgery predated monitoring; and 4 had unsuccessful monitoring. A significant difference was found in hearing preservation rates between the group in whom compound action potential monitoring was performed and those in whom monitoring was either unavailable or failed (p = 0.02). Overall, 38% (30 of 80) had preserved hearing. There were 51 patients in whom the click threshold for the cochlear compound action potential was measured during surgery. Twenty-one patients had a threshold shift of 20 dB or less, 15 (71%) of these retained serviceable hearing (speech reception threshold < or = 50 dB; speech discrimination score > or = 60%). Of 12 patients in whom the threshold shift was 30 to 60 dB, none had serviceable hearing after surgery. The click threshold shift was predictive of a significant postoperative hearing change (p < 0.001). PMID- 7991248 TI - Regeneration of facial nerve after hypoglossal facial anastomosis: an animal study. AB - Hypoglossal-facial nerve anastomosis was carried out in 20 adult guinea pigs. Electromyographic responses of orbicularis oculi muscle evoked by blink reflex were recorded 2, 4, and 6 months after surgery. Then the anastomotic site was reopened, and a segment of buccal branch and the anastomotic trunk were resected for detailed histologic study. Regenerated axons were counted and the cross sectional area of axons and fasciculi was measured. Data obtained from both blink reflex measurement and histologic study demonstrate a good quality of regeneration of the facial nerve from the hypoglossal nerve completed 6 months after the operation. In addition a new nerve bundle was regenerated from the proximal stump of the facial nerve connecting to the anastomotic site in 80% of the animals. Postoperative change in innervation pattern of the facial nerve was also illustrated. PMID- 7991249 TI - Obstructive sleep apnea and the hyoid: a revised surgical procedure. AB - Obstructive sleep apnea syndrome results from a loss of muscular activity of pharyngeal dilators and airway collapse at the hypopharynx-base of tongue or the oropharynx-soft palate. The hyoid arch and its muscle attachments strongly affect hypopharyngeal airway patency and resistance. On the basis of these concepts and previous experience, a modified hyoid suspension procedure is presented. Fifteen consecutively treated surgical patients underwent an isolated modified hyoid suspension procedure to correct hypopharyngeal obstruction. Oropharyngeal-palatal obstruction had previously been corrected or was thought not to be a component of the obstruction. Treatment outcomes were based on objective polysomnographic data and subjective clinical correction of excessive daytime sleepiness. The polysomnographic data included analysis of the respiratory disturbance index and lowest oxyhemoglobin desaturation. On the basis of these criteria, 12 of 15 patients (75%) had correction of their excessive daytime sleepiness and marked improvement in their sleep disorder breathing. The mean preoperative respiratory disturbance index was 44.7 +/- 22.6, and the lowest oxyhemoglobin desaturation was 82% +/- 6%. The postoperative respiratory disturbance index and lowest oxyhemoglobin desaturation were 12.8 +/- 6.9 and 86% +/- 5%, respectively. The modified hyoid suspension procedure appears to offer significant adjunctive treatment for hypopharyngeal obstruction in obstructive sleep apnea syndrome. PMID- 7991250 TI - Analysis of the cocaine metabolite in the urine of patients and physicians during clinical use. AB - Cocaine is considered a superb anesthetic for many otolaryngologic procedures and has been shown to be positive in the urine of patients for up to 72 hours after surgery with a standard radioimmunoassay test. The standard cutoff for drug screening of benzoylecgonine, the main urine metabolite of cocaine, has been 300 ng/ml. However, the new threshold value in many laboratories is now 150 ng/ml. In review of the literature, no study has been performed that quantitates the actual level of the urine cocaine metabolite after a routine otolaryngologic procedure in both physicians and their patients with the gold standard for urine testing, gas chromatography. This study documents the quantitative level of the urine cocaine metabolite in patients and reveals that there are metabolite levels present in physicians during a single exposure, although they are below the current cutoff level that will be picked up on current screening assays. Evidence has also been presented demonstrating a cumulative effect on the benzoylecgonine levels in physicians who clinically use cocaine anesthesia more frequently; these levels can be above the cutoff level on current screening assays. PMID- 7991251 TI - Computer-assisted frontal sinusotomy. AB - An osteoplastic frontal sinus flap with flat obliteration is the "gold" standard for the management of chronic frontal sinus inflammatory disease caused by obstruction of the nasofrontal duct. Frontal sinusotomy, with an osteoplastic technique, call for osteotomies, guided by a template obtained from a Caldwell radiographic view taken at a distance of 6 feet. The reliability of the template depends on the position of the patient, distance at which the radiograph is taken, penetration of the x-rays, and other technical aspects. Therefore the template is a potential source of error. We present the use of a computer assisted frontal sinusotomy as a method to corroborate the shape and margins of the frontal sinus in six patients undergoing obliterative frontal sinus surgery. In our hands, this technique has proved more reliable than the radiographic template to corroborate the positioning of the osteotomies. PMID- 7991252 TI - Hemostatic assessment of patients before tonsillectomy: a prospective study. AB - The purpose of this prospective study in patients undergoing tonsillectomy was to determine whether perioperative bleeding could be predicted by use of a standardized questionnaire concerning bleeding risk combined with measurement of the activated partial thromboplastin time and prothrombin time. Of the 96 patients enrolled in the study, none had a history of a severe bleeding disorder, but 6 (6%) had histories suggestive of a mild bleeding disorder. Further evaluation showed possible von Willebrand's disease in one of these patients. Of the 90 patients with negative questionnaires, 16% had prolongation of the activated partial thromboplastin time. One of these patients had possible von Willebrand's disease. However, none of the patients with positive questionnaires or a prolonged activated partial thromboplastin time bled after surgery. Bleeding that resulted in additional hospital use occurred in 2% of patients, and blood tinged sputum was described by 4% after discharge; all of these patients had negative questionnaires and normal screening studies. The data provide further evidence that routine measurement of the activated partial thromboplastin time and prothrombin time in asymptomatic patients is not useful for predicting postoperative bleeding. In addition, histories suggestive of a mild bleeding disorder are also not accurate predictors of postoperative bleeding. Excessive bleeding associated with tonsillectomy is usually not a result of an identifiable coagulation disorder. PMID- 7991253 TI - Gunshot wounds to the mandible and midface: evaluation, treatment, and avoidance of complications. AB - As American society becomes progressively violent, an ever-increasing number of gunshot wounds are being seen across the United States. Particularly challenging are injuries that involve the mandible and midface, not only because of problems with reconstructing bone and soft-tissue defects but also because of emergent problems with airway obstruction and neurovascular compromise. We present 40 cases of gunshot wounds to the mouth, mandible, and maxilla treated at Wake Forest University Medical Center during the past 7 years. The focus of this retrospective analysis is on emergency evaluation and treatment, complications encountered, and operative techniques used for reconstruction. Special emphasis is placed on recognizing and avoiding the complications of these injuries. PMID- 7991255 TI - Mandible fracture repair: specific indications for newer techniques. AB - Mandible fracture repair is commonly undertaken by otolaryngologists. Although the essential principles of reduction and immobilization are undisputed, the approach used to obtain these goals varies considerably. We performed a critical evaluation of all mandible fractures treated at the Santa Clara Valley Medical Center by the otolaryngology service between January 1988 and February 1992, with the purpose of better defining the indications for plate fixation and for the use of more traditional techniques. One hundred eighty-three fractures in 112 patients were evaluable. Thirty-six (32.1%) of these patients had at least one plate placed (group A); 39 (34.8%) underwent an open procedure, with interosseous wire fixation (group B); and 37 (33.0%) were treated with closed techniques (group C). The severity of fracture (indexed by comminution, presence of infection, teeth in the fracture line, interval to repair, and whether the fracture was open or closed) was similar in plated and nonplated mandibles. Mean (+/- standard deviation) operative times for the three groups were 3.2 +/- 1.6 hours for group A, 3.0 +/- 0.9 hours for group B, and 1.4 +/- 0.5 hours for group C. The number of follow-up visits required was not statistically different (group A, 5.6 +/- 3.8 visits; group B, 5.2 +/- 2.5 visits; and group C, 5.3 +/- 2.0 visits). The overall incidence of major complications was 14.3% (16 of 112), including 11 of 36 (30.6%) in group A, 4 of 39 (10.3%) in group B, and 1 of 37 (2.7%) in group C.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7991254 TI - Comparison of computed tomography and surgical findings in deep neck infections. AB - Computed tomography is routinely used in the evaluation of patients suspected to have deep neck infections. This 10-year retrospective study compares preoperative computed tomography scan reports with intraoperative findings in 38 patients who underwent surgical exploration of the parapharyngeal or retropharyngeal space within 48 hours of their radiographic assessment. Overall, intraoperative findings confirmed computed tomography scan interpretation in 76.3% of the patients. The false-positive rate was 13.2%, and the false-negative rate was 10.5%. The sensitivity of computed tomography scan for detection of parapharyngeal space or retropharyngeal space abscess was 87.9%. This study's documentation of false-positive computed tomography scans in the evaluation of deep neck infections emphasizes the importance of correlating radiologic interpretation with clinical examination before surgical intervention. PMID- 7991256 TI - Outcomes research and otolaryngology. AB - Outcomes research studies the effects of diverse therapies on patient outcome and is increasingly recognized by physicians, third-party payers, and the federal government as crucial for the demonstration of treatment effectiveness and the establishment of patient treatment guidelines. Outcomes research began in the 1970s when researchers studied the geographic variation in the rates and appropriateness of various surgical procedures, including tonsillectomies. Outcomes research is different from traditional clinical research because it addresses a wide variety of issues pertaining to health care delivery, strategy, and policy. To address these issues, outcomes research uses two principal methodologic approaches: (1) nonrandomized research methods and (2) expanded descriptions of patient outcomes. The methodologic requirements for outcomes research include (1) establishment of the diagnostic criteria for the disease under study, (2) creation of clinical-severity index for prognostic stratification, (3) identification and measurement of cogent comorbid conditions, and (4) establishment of outcomes that include descriptions of health status, quality of life, satisfaction with care, and medical costs. Many diseases within otolaryngology seem appropriate for outcomes research. Because prospective outcomes research is conducted with patients treated in the community, great opportunity exists for community-based physicians to become involved in this type of research. PMID- 7991257 TI - A preliminary study of the prognostic role of electromyography in laryngeal paralysis. AB - Confidence in the reliability of laryngeal electromyography to predict recovery is critical if this tool is to be used to select the type and timing of surgical intervention. The characteristics of electromyography of 14 patients with unilateral vocal fold paralysis were assessed to determine which factor or combination of factors would be most useful in determining prognosis. We examined the duration, amplitude, waveform morphology, root-mean-square, and time interval from onset to electromyography recording. The results supported the concept that electromyography recordings are valuable in determining prognosis if performed before 6 months and preferably within 6 weeks of onset of laryngeal paralysis. A positive prognosis for laryngeal recovery was indicated when the following electromyography features were present in the immobile vocal fold: (1) normal motor unit waveform morphology, (2) overall electromyography activity characterized by a root-mean-square value greater than 40 microV in any one task, and (3) no electrical silence during voluntary tasks. On the basis of this criteria our overall correct prognostic rate was 89%. PMID- 7991258 TI - Transient positioning of a silicone T tube in frontal sinus surgery. AB - We applied transient positioning of a silicone T tube in 18 patients with frontal sinus cysts. Inflammation in the nasal cavity usually subsided within 6 months of surgery, whereas the frontal sinus showed pathologic changes in more than half of the patients even 6 months after surgery. After removal of the tube, the nasofrontal passage remained open in 16 patients who obtained good aeration with an intact mucosal lining in the frontal sinus, but it eventually closed in the remaining 2 patients who failed to obtain good aeration. This finding suggests that persistent inflammation in the frontal sinus encourages the closure of the nasofrontal passage and that transient positioning of a silicone T tube is successful if it is removed after subsidence of inflammation in the sinonasal tract. PMID- 7991259 TI - Intranasal sphenoethmoidectomy: an evolution of technique. AB - Intranasal sphenoethmoidectomy was originally used primarily for the provision of adequate drainage of acute and subacute bacterial sinusitis. However, the spectrum of inflammatory sinus disease has changed dramatically since the popularization of broad-spectrum antibiotics, and chronic hyperplastic rhinosinusitis has replaced acute sinusitis as the primary indication for ethmoidectomy. In such cases total or almost total disease removal is crucial to providing long-term drainage and ventilation. We describe several modifications of the Yankauer sphenoethmoidectomy technique that enable the sinus surgeon to provide clearance of disease and excellent drainage for all sinuses by complete marsupialization of the sphenoid, ethmoid, and maxillary sinuses. These modifications include (1) complete rather than partial removal of the middle turbinate, (2) extended middle meatal antrostomy with palatine bone resection to the pterygoid process with delineation of the inferior and medial orbital wall, and (3) introduction of operative endoscopes as adjunctive tools in areas inaccessible to conventional visualization. The current technique and results in nearly 2000 procedures are described. PMID- 7991260 TI - Technique for injection of botulinum toxin through the flexible nasolaryngoscope. AB - A new endoscopic method of injecting botulinum toxin into the thyroarytenoid muscles for treatment of adductor spasmodic dysphonia was evaluated. Twelve patients with adductor spasmodic dysphonia were given injections in the thyroarytenoid muscle under video visualization with a flexible catheter needle that was passed through the working channel of a flexible nasolaryngoscope. Six patients received unilateral injections, and six received bilateral injections. Preinjection and postinjection speech samples were compared by use of spectrographic analysis. Significant decreases in voice breaks and sentence duration were found after treatment with both unilateral and bilateral injections. Patient interviews and diaries documented the reported degree and duration of symptom reduction. All 12 patients reported that the injections were of significant benefit and that the endoscopic procedure was tolerable. We concluded that this is a safe and effective technique for injecting botulinium toxin into laryngeal muscles for treatment of spasmodic dysphonia. PMID- 7991261 TI - Vasoconstrictive effects of cocaine and lidocaine with epinephrine in the hamster cheek pouch model. AB - Otolaryngologists frequently use cocaine and lidocaine with epinephrine for their anesthetic and vasoconstrictive effects. However, no studies have visually compared the vasoconstrictive effects of cocaine to lidocaine with epinephrine. This study used the everted hamster cheek pouch model to assess the vasoconstrictive effects of cocaine and lidocaine with epinephrine by measuring the diameter changes of arterioles. Our results showed that locally injected 1% lidocaine with 1:100,000 units epinephrine caused the greatest diameter reduction in arterioles to 32% of the initial resting diameter. Topical 1% lidocaine with 1:100,000 units epinephrine caused a gradual reduction in diameter with findings equivalent to those of injected 1% lidocaine with 1:100,000 units epinephrine at 30 minutes. Topical 5% cocaine HCl showed a minimal response, with a reduction to only 85% of the resting arteriolar diameter. Topical NaCl and injected NaCl controls showed no significant arteriolar reduction. Vasoconstrictive differences between the preparations were statistically significant (p < 0.05). Five percent cocaine is a much weaker vasoconstrictor than locally injected 1% lidocaine with 1:100,000 units epinephrine. PMID- 7991262 TI - Scanning electron microscopic evaluation of age-related changes in the rat vestibular epithelium. AB - An ultrastructural study was performed to assess age-related changes in the vestibular end organs of Fischer 344 rats. The surfaces of the maculae and cristae from 3-, 12-, and 24-month-old Fischer 344 rats were observed by use of scanning electron microscopy. Age-related changes in the morphology of the vestibular neuroepithelium included a substantial loss of hair cells, as well as a reduction in the number of kinocilia and stereocilia on those that remained. These changes were greatest in the central upper regions of the three ampullae. In aged animals a greater area of the neuroepithelial surface was covered with microvilli, and in some instances, giant cilia were found among the microvillous surfaces. In contrast, there were few differences among the three age groups in the number and condition of hair cells in the saccules and utricles. The changes observed in the cristae may contribute to the age-associated impairment of vestibular function. If similar changes occur in human beings, these could in part account for the presbycusis observed in the elderly. PMID- 7991263 TI - A pressure-regulated model of normal and pathologic phonation. AB - Recent evidence suggests that the lung-thorax system functions as a constant pressure source during phonation. However, previous animal models used a constant flow source. This article describes an in vivo canine model that maintains a constant subglottic pressure during phonation to more closely simulate the pulmonary system. At any given subglottic pressure, increasing levels of recurrent laryngeal nerve stimulation resulted in a significant rise in resistance followed by a plateau. Increasing levels of superior laryngeal nerve stimulation, however, produced no significant change in glottal resistance. Three experimental conditions were studied: normal, unilateral recurrent laryngeal nerve paralysis, and paralysis followed by arytenoid adduction. In normal canines, maximal vocal efficiency values were the highest, indicating the best match between pressure and resistance. The vocal efficiency values were significantly lower in recurrent laryngeal nerve paralysis, indicating pressure resistance mis-match. Arytenoid adduction increased the maximal vocal efficiency values and decreased the mismatch observed in the paralyzed state. These findings may provide insight into an understanding of normal and pathologic laryngeal behavior. PMID- 7991264 TI - Laryngeal squamous cell carcinoma metastatic to the pituitary gland: a case study. PMID- 7991265 TI - Primary nasopharyngeal tuberculosis: a case report and review of this rare entity. PMID- 7991266 TI - Intradiploic epidermoid of the temporal bone: case history and literature review. PMID- 7991267 TI - Thyroid abscess resulting from fine-needle aspiration. PMID- 7991268 TI - Intrasphenoidal encephalocele: diagnosis and management. PMID- 7991269 TI - Nasal obstruction and Horner's syndrome. PMID- 7991270 TI - Disposable pressure infusor for surgical neck extension. PMID- 7991271 TI - The airway scale: a simple tool for comparing calibers of airway devices. PMID- 7991272 TI - Portable telemetry system for electromyography. PMID- 7991273 TI - Middle ear anomalies. PMID- 7991274 TI - Assessment of lectin binding for prognosis in endometrial carcinoma. AB - The binding of Ulex europeus agglutinin-I (UEA-I) and Peanut agglutinin (PNA) was studied in 56 endometrial carcinomas. The positive rates of UEA-I and PNA were 66%. Following neuraminidase treatment, the PNA positive rate increased from 66% to 98% and most tumors stained abundantly. UEA-I staining was unaffected. Using a combined grading system based on architectural and nuclear abnormalities, the PNA positive rates of grade 1, grade 2 and grade 3 tumors were 78%, 70% and 36%, respectively. There was no correlation between UEA-I binding and the grading systems. UEA-I binding correlated significantly with the presence of myometrial invasion and vessel permeation. Metastatic endometrial carcinomas showed a high affinity of tumor cells for UEA-I. Tissues that stained with UEA-I were those from patients with the worst prognosis. PNA and UEA-I reactivities relate to the biologic activity of endometrial carcinomas. UEA-I can serve as a prognostic marker for patients with endometrial carcinoma. PMID- 7991275 TI - Clear cell ("sugar") tumor of the lung is a lesion strictly related to angiomyolipoma--the concept of a family of lesions characterized by the presence of the perivascular epithelioid cells (PEC). AB - We report a comparative study of 3 clear cell tumors of the lung (CCTL) and 3 angiomyolipomas (AML) of the kidney. Morphological analysis shows that the cells of CCTL are identical to the perivascular epithelioid component of AML. Phenotypically they both consistently expressed melanoma-associated antigens recognized by Moabs HMB45 and HMSA-1, while they were negative for HMSA-5. A minority of cells also expressed S-100 protein, vimentin and actin. In addition, one case of CCTL showed mature adipose tissue entrapped in the proliferation, thus suggesting an intermediate form between CCTL and AML. Based on morphological and phenotypical similarities, it is suggested that CCTL and AML belong to the same family of lesions, characterized by the presence of a peculiar muscle cell, expressing different melanoma-associated antigens. PMID- 7991276 TI - Malignant mixed tumor of the skin (malignant chondroid syringoma). AB - Two cases of malignant mixed tumor of skin were studied, one of which demonstrated regional metastasis. The immunohistochemical features of these 2 neoplasms and of the 2 malignant mixed tumors previously described in Western Australia indicate that these neoplasms show eccrine differentiation and suggest their origin from both the secretory and ductal segments of the gland. The histological criteria of malignancy are discussed, with particular reference to those features which indicate malignant potential in neoplasms which otherwise lack overt morphological criteria of malignancy. PMID- 7991277 TI - Neurocysticercosis: a report of four cases. AB - Cysticercosis is an uncommon disease in Australia. Only 4 cases of neurocysticercosis were found in our hospital with an active neurosurgical service over a 10 yr period. All 4 cases were migrants, 3 from South America and one from Cyprus. Epilepsy, aseptic meningitis and raised intracranial pressure were the common symptoms. Although the cerebral lesions were seen on CT scans, misinterpretation of the X-ray appearances readily occurs and the diagnosis can only be confirmed by histopathological examination of tissues. The pathological features are described including electron microscopy of one case. The cysticercus has a unique ultrastructure which is most helpful in establishing the diagnosis in cases were tissue sample is small and light microscopy is difficult. Neurocysticercosis can masquerade as a glioma or other space occupying lesion or aseptic meningitis. This condition should be considered in obscure neurological syndromes in migrants from affected regions of the world. PMID- 7991278 TI - Histopathological prediction of hepatitis B recurrence in liver allografts. AB - The aim of this study was to review the clinical, serological and histopathological features of 20 patients who underwent orthotopic liver transplantation for hepatitis B virus (HBV) related liver disease in an attempt to identify factors which predict recurrence of HBV infection, pattern of disease and disease severity. Hepatitis B recurrence occurred in 11 patients (55%). Positive immunoperoxidase staining for HBsAg and HBcAg of the hepatectomy specimen were shown to have a sensitivity (82% and 64% respectively) and specificity (55% and 66%) in predicting recurrence. This was comparable to serological markers such as HBV DNA (36% sensitivity and 89% specificity). The staining for HBcAg in some cases was weak, focal and had a reticular pattern. Therefore, examination of multiple blocks with a high magnification was necessary to detect HBcAg staining. Negative staining of multiple sections for HBsAg and HBcAg were shown to have a good correlation with clearing of HBV infection (5 out of 6 patients). If recurrence occurred, the range of histological and clinical patterns of HBV recurrence was varied, with severe disease occurring in 5 patients. Neither pre-transplant serology nor hepatectomy immunoperoxidase staining characteristics were shown to be of value in predicting the pattern or the severity of disease once HBV recurrence had occurred. This study indicates that lack of staining for HBV antigens on multiple sections of the native liver may predict a subgroup of HBsAg positive transplant patients who will not suffer from recurrent disease. Once disease did occur however, markers for severity of recurrence were not identified. PMID- 7991279 TI - Actinomycin D associated hepatic veno-occlusive disease--a report of 2 cases. AB - Until recently, actinomycin D (AMD), a cytotoxic antibiotic, was considered to cause little or no liver damage. There are now reports of liver failure following treatment of childhood cancers with AMD. This report describes the pathological changes in liver biopsy samples taken from 2 children who developed liver failure after combined chemotherapy for Wilms' tumor. The changes were those of nodular hyperplasia, sclerosis of terminal hepatic venules with associated zone 3 hemorrhagic necrosis, and sinusoidal fibrosis. These features were initially ascribed to the veno-occlusive disease caused by pyrrolizidine alkaloids, radiotherapy and some therapeutic drugs but have not been described in detail as a complication of AMD therapy. An additional feature peculiar to these 2 cases was the presence of unexplained extramedullary hematopoiesis. PMID- 7991281 TI - Southern blot analysis of lymphoproliferative disorders: use and limitations in routine surgical pathology. AB - Antigen receptor gene rearrangement studies are a sensitive means of determining lineage and clonality in lymphoproliferative disorders (LPDs) which remain difficult to classify after assessment of morphology and immunohistochemistry (IHC). This study investigates the utility of genotyping LPDs in a surgical pathology laboratory servicing a large teaching hospital. Ninety-eight specimens with detailed frozen (FS) and/or paraffin section IHC were studied, including 65 B-cell lymphomas, 14 T-cell lymphomas, 2 biopsies of T-zone dysplasia, one unclassifiable lymphoma, 8 Hodgkin's disease (HD) and 8 reactive nodes. Southern blotting (SB) was performed on tumor and control DNA cleaved with restriction enzymes EcoR1, Hind III and BamH1, using radiolabelled probes for the immunoglobulin heavy chain joining region, constant regions of kappa and lambda light chains, and the constant region of the T-cell receptor beta chain. All reactive nodes and those harbouring HD and DNA in the germline configuration, apart from JH rearrangement in one case each of HD and florid reactive hyperplasia. Of the non-Hodgkin's lymphomas (NHL), 17% did not reveal clonal rearrangements (11% B-NHL; 44% T-NHL). Most of the negative results could be explained by sampling error in partially involved nodes, highly polymorphous infiltrates where the neoplastic population may have been below the 1% threshold detectable by SB, and instances of anaplastic large cell lymphoma. After accounting for these cases, a 5% negative rate of genoclonality remained (3% B NHL; 13% T-NHL). In the majority of NHL (95%), the diagnosis could be established on the basis of morphology and/or IHC alone.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7991280 TI - Analysis of cerbB2 expression using a panel of 6 commercially available antibodies. AB - Results are presented of a study comparing cerbB2 (neu or Her2) expression as assessed immunohistochemically in breast neoplasia using a panel of 6 commercially available antibodies. The antibodies were examined utilizing conventional formalin fixed paraffin embedded tissue, and compared with molecular analysis of gene amplification. The aim was to determine the practical utility of each antibody, assessing ease of use, specific and non-specific staining characteristics, and expense, thus allowing a specific recommendation as to antibody of choice for immunohistochemical assessment of cerbB2 expression. Reassuringly, amongst the 38 breast lesions (36 carcinomas, 2 fibroadenomas) subjected to immunohistochemically (IHC) with the panel of 6 antibodies (Ab), no gross discrepancy of staining pattern was seen. Of the 38 cases, 10 were positive (26%), where at least one Ab demonstrated clear cytoplasmic membrane staining. Of a total of 45 breast lesions (43 carcinomas, 2 fibroadenomas), including all those examined by IHC, the total number of cases showing cerbB2 amplification by DNA analysis was 14 (31%). Using the DNA amplification as a base line for comparison, one Ab (No. 4) was found to stain 6 of the 14 cases of breast carcinoma that were assessed as showing amplification at the DNA level. Four Abs (1,3,5,6) stained 5 of these cases. However, Abs 3,4 and 6 displayed artefactual cytoplasmic staining (in the absence of membrane staining) that precluded the practical use of these reagents. Therefore, based on additional considerations of cost and ease of use, Ab No. 1 was finally chosen for recommendation from the 6 Ab panel. PMID- 7991282 TI - Autoerotic deaths: four cases. AB - We describe the circumstances and post mortem medical findings of 4 unusual fatalities where death occurred during autoerotic practice. Three cases occurred in young to middle-aged men--hanging, electrocution and inhalation of a zucchini. The manner of death in each was accidental. The fourth case was an elderly man who died of ischemic heart disease, apparently whilst masturbating with a vacuum cleaner and a hair dryer. PMID- 7991283 TI - The value of Medicare statistics in monitoring Pap smear screening. Screening versus non-screening smears: the role of the laboratory. AB - In November 1991 separate Medicare item numbers were introduced to distinguish screening from non-screening cervical smears for the purposes of monitoring the screening programme. Referring doctors are now expected to indicate the appropriate item number on the request form accompanying the Pap smear. To test compliance with this requirement, we examined 1000 consecutive request forms for cervical smears received in August 1993. We found that 22.7% had no item number indicated and that for a further 10.4% the item number given appeared to be incorrect. As the account issued by the laboratory must show an item number the ultimate responsibility for the choice of the item number rests with the laboratory. Using the guidelines supplied by Medicare, we formulated detailed criteria to classify smears as screening or non-screening, based on the patient's past smear history and/or clinical information provided by the referring doctor. Applying these criteria to cervical smears received in this laboratory in 1993 resulted in 70% being classified as screening and 30% as non-screening smears. Analysis of the cytological predictions for these smears showed substantially higher rates for all grades of abnormalities in the non-screening smears, thus lending support to the validity of our classification system. We conclude that classifying smears into screening and non-screening categories provides valuable information for statistical and quality assurance purposes but can only be useful for monitoring purposes if the criteria for assigning smears are applied consistently by all doctors and laboratories. PMID- 7991284 TI - Test and teach. Number Seventy-six. Diagnosis: Pseudomyxoma peritonei arising from appendical cystadenocarcinoma. PMID- 7991285 TI - Test and teach. Number Seventy-seven. Diagnosis: Kimura's disease. PMID- 7991286 TI - Cross-matched platelets in bone marrow transplantation. AB - Antibodies to HLA-antigens remain a problem in multiply-transfused patients. Over a 2 yr period 44 bone marrow transplant recipients were screened at weekly intervals for the presence of HLA-antibodies using a solid phase red cell adherence technique. An adaptation of this method was used to provide cross matched random donor platelets (XMRDP) when screening proved positive. Twelve of the 44 patients were antibody positive, 6 prior to transplantation and 6 following the transplant. Those 4 patients who developed an antibody following the transplant had a significant increase in platelet increments following the change from random donor platelets (RDP) to XMRDP even though only one patient was refractory to platelets at the time the antibody was first detected. No significant bleeding occurred during the study period. The use of routine platelet antibody screening followed by platelet cross-matching allows excellent support of thrombocytopenic patients without requiring HLA-typed blood donors and avoiding clinical platelet refractoriness. PMID- 7991287 TI - Erythrocyte creatine levels in hyperthyroidism. AB - The mechanism by which erythrocyte mean corpuscular volume (MCV) is decreased in hyperthyroidism is not known. One possible mechanism is premature aging of erythrocytes in the circulation. Since erythrocyte creatine has been shown to be a good marker of cell senescence, we determined this in hyperthyroid patients and control subjects to examine whether the decrease in MCV is related to senescence. Erythrocyte creatine levels were similar in both hyperthyroid patients and controls, suggesting that premature senescence of erythrocytes does not account for the lower MCV in hyperthyroidism. PMID- 7991288 TI - Feto-maternal alloimmune thrombocytopenia associated with anti-HPA-5a--the first Australian case. AB - Maternal alloantibodies to platelet specific antigens are a rare but important cause of severe thrombocytopenia in the fetus and neonate. Feto-Maternal Alloimmune Thrombocytopenia (FMAT) is most often due to anti-HPA-1a (PLA-1) or anti-HPA-5b (Bra). Anti-HPA-5a (Brb) however is extremely uncommon, with only 4 cases previously described. We report the first Australian case of feto-maternal alloimmune thrombocytopenia due to anti-HPA-5a. PMID- 7991289 TI - Xylene: its toxicity, measurement of exposure levels, absorption, metabolism and clearance. AB - Xylene is an aromatic hydrocarbon widely used in industry and medical technology as a solvent. Health and safety authorities in most countries, including Australia, recommend a threshold limit value (TLV) of 100 ppm in the working environment. Recently, the amount of the major metabolite of xylene, methylhippuric acid (MHA), in urine has been recommended as a better indicator of exposure. The American Conference of Governmental Industrial Hygienists has recommended an upper limit for this indicator, called a biological exposure index (BEI), of 2.0 g MHA/L urine (SG 1.016). Xylene vapour is absorbed rapidly from the lungs, and xylene liquid and vapour are absorbed slowly through the skin. Of the xylene absorbed, about 95% is metabolised in the liver to MHA and 70 to 80% of metabolites are excreted in the urine within 24 hours. However, the many variables which affect the absorption, metabolism and clearance of xylene include exercise, alcohol intake, cigarette smoking, co-exposure to other solvents, gender, and gastrointestinal, hepatic and renal pathology. Xylene in high concentrations acts as a narcotic, inducing neuropsychological and neurophysiological dysfunction. Respiratory tract symptoms are also frequent. More chronic, occupational exposure has been associated with anemia, thrombocytopenia, leukopenia, chest pain with ECG abnormalities, dyspnea and cyanosis, in addition to CNS symptoms. Concomitant exposure to xylene and other solvents, including toluene, affected hematological parameters, liver size, liver enzymes, auditory memory, visual abstraction, and vibration threshold in the toes. Normal metabolic pathways were altered and significant increases in some serum bile acids may reflect early liver damage.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7991290 TI - Seven patients with respiratory infections due to Corynebacterium pseudodiphtheriticum. AB - Seven cases of lower respiratory tract infection due to Corynebacterium pseudodiphtheriticum are described. Lower respiratory tract infections with C. pseudodiphtheriticum in immunocompetent patients are usually associated with pre existing chronic pulmonary disease, and are sometimes associated with endotracheal intubation. Antimicrobial susceptibility testing of these isolates showed uniform sensitivity to penicillin and variable results to erythromycin. PMID- 7991291 TI - Serotype and serosubtype distribution of strains of Neisseria meningitidis isolated in South Australia and the Northern Territory of Australia: 1971-1989. AB - Strains of meningococci isolated from patients in South Australia (SA) and the Northern Territory (NT) with either bacteremia or meningitis (or both) were serotyped and serosubtyped using monoclonal antibodies in a whole cell ELISA technique. From SA, 144 isolates were examined for the period 1971 through 1989 and from the NT, 38 isolates from 1975 through 1977 and 1983 through 1989 were examined. During the periods of study the principal serogroups were group B in South Australia and group A in the Northern Territory. About 60% of the SA strains were typable and subtypable: the predominant types were 4, 2a, 15 and 14, in that order; the predominant subtypes were P1.2, P1.1 and P1.10, in that order. Of the strains from the NT about 80% were typable, the predominant type was type 4 and all 19 group A strains were identified as type 4, subtype P1.10. PMID- 7991292 TI - The antibiotic susceptibilities of Xanthomonas maltophilia and their relation to clinical management. AB - An increase in recovery of Xanthomonas maltophilia from clinical specimens at our institutions prompted, amongst other measures, an investigation of the antibiotic susceptibility patterns of the organism. Fifty-five consecutive first isolates of Xanthomonas maltophilia were obtained and antimicrobial susceptibility tests were carried out by the agar dilution method. Trimethoprim/sulfamethoxazole was the most active antimicrobial agent (94% susceptible), with 71% susceptible to ticarcillin/clavulanic acid, 56% susceptible to ciprofloxacin and 49% susceptible to ceftazidime. Amoxycillin/clavulanic acid and imipenem were inactive (0% susceptible), while aminoglycosides were effective against only 7% of isolates. Potentiation was observed with both the combination of trimethoprim and sulfamethoxazole and the combination of ticarcillin and clavulanic acid. Familiarity with the antibiotic susceptibility pattern of Xanthomonas maltophilia as well as the potential shortcomings of the in vitro susceptibility data are important in the effective clinical management of Xanthomonas maltophilia infections. PMID- 7991293 TI - Pyemotes species strongly implicated in an outbreak of dermatitis in a Queensland country hospital. AB - An acute outbreak of itchy papulovesicular dermatitis occurred among nursing home patients in a small Queensland country hospital west of Toowoomba. Mites, Pyemotes species, were found in the immediate environment of the hospital and have been implicated as the causative agent. This case illustrates the importance of examination of environmental specimens for ectoparasites in cases of unexplained dermatoses. PMID- 7991294 TI - Aneuploid islet cell tumor with late metastasis. AB - An unusual case of insulin producing islet cell tumor is reported which recurred after a 16 yr interval. In most instances malignancy of islet cell tumors is impossible to assess morphologically or functionally but depends on the recognition of metastases. Nuclear DNA analysis provides significant prognostic and biological information in a number of solid human tumors. Retrospective computerized nuclear image analysis of the primary tumor in the present case showed an aneuploid DNA profile similar to that seen in the metastasis. It appears that ploidy studies may be useful in predicting malignant potential of islet cell tumors. PMID- 7991295 TI - Primary Sjogren's syndrome and gamma heavy chain disease. AB - We describe a patient who has primary Sjogren's syndrome associated with asymptomatic gamma heavy chain disease and a tubulointerstitial nephritis. Sjogren's syndrome is known to be complicated by lymphoproliferative disorders and tubulointerstitial nephritis but gamma heavy chain disease is rare (approximately 100 cases described). There is one previously reported case of gamma heavy chain disease associated with primary Sjogren's syndrome and 2 cases associated with secondary Sjogren's syndrome. Our patient and the 3 other patients described in the literature did not have evidence of an underlying lymphoproliferative disorder. PMID- 7991296 TI - Subungual exostosis in a young woman. AB - A case of Dupuytren's exostosis arising under the left great toenail of a 12 yr old girl following an episode of trauma 5 mths earlier is reported. These lesions, occurring predominantly in young adults and usually affecting the great toe, have a propensity for local recurrence. The radiological and histological features and differential diagnosis are discussed. PMID- 7991297 TI - Examination of lungs for asbestosis and asbestos bodies. PMID- 7991298 TI - Splenic littoral cell angioma, not bacillary angiomatosis. PMID- 7991299 TI - Do how-to-commit-suicide manuals increase the suicide rate? PMID- 7991300 TI - Effects of sex and sex roles on avoidance of same- and opposite-sex touch. AB - Touch and touch avoidance are important facets of interpersonal relations. Touch avoidance has been related to sex, but the relationship between touch and sex roles has not been widely substantiated. 259 undergraduate students participated in a procedure designed to test the relationship between sex, sex roles, and same sex and opposite-sex touch avoidance. Significant differences were reported between men and women on same-sex touch avoidance but not on opposite-sex touch avoidance. Participants high on androgyny reported less same-sex and opposite-sex touch avoidance than did subjects low on androgyny. No interactive effect between sex and androgyny was found for either same-sex or opposite-sex touch avoidance. Regression procedures indicated predictive models for sex and androgyny in relation to same-sex and opposite-sex touch avoidance. Specific conclusions regarding the relationships among sex, androgyny, and touch avoidance were stated. PMID- 7991301 TI - Draw-A-Person test as a measure of anxiety in the work place. AB - It was hypothesized that, given their stressful working conditions, nuclear weapons workers would show more anxiety indicators on the Draw-A-Person test. Three groups (ns = 9) were given the test and their drawings were scored with Handler's 1967 objectively scorable indexes. A posttest-only design with two nonequivalent comparison groups was employed. Nuclear weapons workers had a reliably higher number of anxiety indicators on their Draw-A-Person drawings than the two comparison groups. These preliminary results indicate that Handler's objectively scorable indexes may be of value in detecting anxiety in the work place. The conclusions are tempered by the small groups and the quasi experimental design used but indicate that further research could be fruitful. PMID- 7991302 TI - Psychometric properties of Russell's short form of the Booklet Category Test. AB - Russell's short form of the Booklet Category Test was administered to 26 diagnosed schizophrenic patients and 14 normal individuals along with a test of premorbid intelligence. IQ correlated significantly (inversely) with errors and in particular with Subtests 3, 4, and 6. Age related directly to errors, especially for Subtests 3, 4, and 5. The mean Cronbach coefficient alpha was .71, indicating moderate item homogeneity across subtests. In sum, the shortened form appears to be an efficient and effective measure of concept formation among schizophrenic individuals. PMID- 7991303 TI - Motion aftereffects of wagon wheels: motion aftereffects follow apparent rather than real movement. AB - Power and Moulden have proposed a model which accounts for the movement of gratings in apertures including the barber pole illusion. It predicts the direction of motion aftereffects which follow from perceived veridical motion and the direction of these aftereffects which follow from the illusory movement experienced during the barber pole illusion. At a perceptual level, the model predicts motion aftereffects will follow direction of apparent movement rather than veridical direction. Four experiments tested this prediction. In Exp. 1 a spiral was viewed under flickering light so it appeared to be moving in the direction opposite to true motion, and the aftereffect was opposite to the apparent direction. In Exp. 2 the spiral was viewed through a narrow aperture so that it was effectively a grating appearing to move in the opposite direction to veridical motion. Again, the motion aftereffect was opposite to the apparent rather than true direction of rotation. In Exp. 3 a sectored disc was used, and similar results were obtained. In Exp. 4 the sectored disc was videotaped so that it appeared to be rotating in the direction opposite to true motion. The after motion to this "wagon wheel" effect was opposite to its apparent direction of rotation on the screen. In all experiments the predictions were confirmed, thereby confirming the general principle that motion aftereffects follow apparent rather than real direction of movement. PMID- 7991304 TI - Execution-time updating of motor program for rapid serial output. AB - Motor program updating was studied by asking 2 subjects to modify the accent pattern of rapid finger-tapping sequences during execution. The tap to be accentuated was changed unpredictably in one-third of the trials; on these trials the signal indicating the new accent position was delivered upon the onset of the first tap. The probability of placing the new accent correctly increased when the tap to be accentuated was shifted towards the end of the sequence. The probability of cancelling the initially prepared accent showed a similar pattern. Successful updating of the accent pattern could be achieved without any mistiming of the successive taps. These findings are taken to indicate the existence of a temporal overlap between the execution of the initial part of the sequence and the programming of the later part. PMID- 7991305 TI - Zipf's law extended to small samples of adult speech. AB - Zipf's law related the frequencies of words found in speech samples to the numbers of different words at each frequency. The present study extended this law to very small samples (400 words) of both written and oral speech. A secondary purpose was to investigate whether oral and written samples from the same speakers deviate from Zipf's law in systematic ways, allowing correct identifications of speakers across the two modalities. Zipf's law was strongly confirmed, but systematic deviations from the generalization proved difficult to demonstrate. PMID- 7991306 TI - Implicit and explicit learning: differential effects of affective states. AB - Two experiments using a standard artificial grammar paradigm were conducted to examine the role of affective states, specifically anxiety and depression, on implicit learning. The main purpose was to broaden the range of human functioning explored through the application of the robustness principle in the evolutionary framework recently developed by Reber which predicts that cognitive processes which rely upon unconscious, implicit processes should be less affected by affective states than those which rely upon conscious, explicit processes. In Study 1 (N = 60), high test anxiety was associated with performance deficits in the explicit components of the task; no differences were found in the implicit phases of the task. In Study 2 (N = 160), varying levels of subclinical depression were unrelated to both implicit and explicit functioning. The contrasting findings of the two studies are discussed in terms of the differential cognitive effects and adaptive implications of these two affective states. PMID- 7991307 TI - Cable television home-shopping stations and disabled persons: an informal look. AB - Based in part as a service to handicapped people, the Federal Communications Commission has granted "must carry" protection to cable television home-shopping stations. An informal inquiry of the product mix presently being offered does not show that this mission is being fulfilled. PMID- 7991308 TI - Mood alterations in older adults following acute exercise. AB - Limited research indicates positive affective change following acute bouts of exercise, but whether this improved affect among younger subjects may be generalized to older individuals is not known. The present study, then, examined the effects of a single bout of physical activity among older participants. 16 trained women (Mage = 64.5 +/- 7.6 yr.) completed an abbreviated Profile of Mood States prior to and immediately following a 75-min. session of aerobic line dancing. A series of one-way analyses of variance with repeated measures were used to examine differences between pre- and posttest subscores on mood states. Significant decreases following exercise in scores on Tension, Depression, Fatigue, and Anger and a significant increase in scores on Vigor relative to preexercise (control) scores were found. Global mood was significantly improved after the exercise session. No significant difference was found between pre- and postexercise measures of Confusion. Previous findings of significant improvements in affect immediately after an acute bout of exercise may be generalized to older adults. Repetition with a nonexercised control group is desirable. PMID- 7991309 TI - Students' learning of volleyball skills. AB - An examination of 222 students' learning of skill in volleyball was conducted in classes. Analysis indicated that over an eight-lesson unit performance for both serve and forearm pass improved. When classes were the unit of analysis five classes showed significant improvement on the serve and four on the pass. Present data provide a base for study of instructional effectiveness in physical education. PMID- 7991311 TI - Salty solutions: their effects on thermal set points in behavioral repertoires of albino rats. AB - Salt (sodium chloride) has been linked to increased blood pressure and a rise in core body temperature. The objective of this study was to investigate the role played by salt in altering behavioral thermoregulation in albino rats. Different doses of sodium chloride were administered (ip) prior to fixed-interval 2-min. schedules of microwave reinforcement in rats tested in a cold Skinner Box. Three Sprague-Dawley rats were conditioned to regulate their thermal environment with 5 sec. exposures of MW reinforcement in a repeated-measures reversal design. Friedman's non-parametric test showed significant differences among sodium chloride doses and physiologically normal saline. Post hoc sign tests showed that all doses of NaCl suppressed operant behavior for heat except 60 mg/kg. The hypothesis that sodium chloride lowers hypothalamic set point for heat was partially supported. PMID- 7991310 TI - Interrelation between stress and coaches' behavior during rest periods. AB - The purpose of the present investigation was to examine the interrelation between stress and coaches' behavior during rest periods. Subjects were 154 German coaches who completed the Rest Period Questionnaire and a Bibliographic Questionnaire for Coaches designed to attribute stress to coaches' behavior during rest periods. Analysis indicated that coaches who are highly stressed by the practice rate themselves significantly less active and less authoritarian during rest periods than do their low stressed colleagues. In addition, coaches who are highly stressed by the competition rate themselves significantly less warm-hearted than the low stressed group. PMID- 7991312 TI - Response velocity, range of movement, and timing accuracy. AB - This study examined the relationship between variation in response velocity, range of motion, and temporal accuracy for 25 subjects executing stroking movements aimed to terminate coincidently with a moving stimulus arriving at a target. Analysis indicated that temporal accuracy improved with increasing velocity and decreasing range of movement. PMID- 7991313 TI - Differences among slopes and intercepts for regression lines predicting children's connotative and denotative knowledge of familiar and unfamiliar words on the basis of age. AB - 90 children from Grades 2, 4, and 6 were asked to define words and to rate them in terms of emotional meaning. Significant differences among criterion means and among slopes and intercepts of lines predicting definitional and emotional accuracy on the basis of age suggest that knowledge about the pleasantness of familiar words (pleasantness accuracy) begins early, is high, and asymptotes earlier in comparison to definitional knowledge or to the WISC-R Vocabulary subtest in which knowledge (accuracy) begins to grow at a later age, grows faster, and does not reach the same over-all mean. PMID- 7991315 TI - Visual preferences of Mexican preschool children for abstract and realistic paintings. AB - 51 Mexican children ages 3 and 4 years were asked to express preferences for 9 abstract and 9 realistic paintings on two separate occasions. Consistently, the children showed no clear preferences for abstract or realistic paintings and their choices remained stable. Implications for educational and cultural environments as well as children's literature are discussed. PMID- 7991314 TI - Use of assisted reading to improve reading rate, word accuracy, and comprehension with ESL Spanish-speaking students. AB - The present experiment examined the effectiveness of an assisted reading program on reading rates and comprehension of three Spanish-speaking students learning English. The effects of assisted reading on reading rate, word accuracy, and comprehension were examined using a multiple-baseline design across individuals. Increases in words read correctly per minute with repeated readings of the passage and on new passages, decreases in errors per minute, and increases in comprehension were noted. PMID- 7991316 TI - Effects of "parental filter" on reported vividness of imagery. AB - 127 undergraduates (66 women, 61 men) completed experimental forms of Ahsen's Adapted Vividness of Visual Imagery Questionnaire (AA-VVIQ) in which the 16 items of Marks' Vividness of Visual Imagery Questionnaire (VVIQ) are rated separately with either mother or father in mind. When the two ratings were made side-by-side for each item and those for the father filter were given first, there was some evidence of dimmer father- than mother-filtered imagery for women. However, this effect did not appear when the mother-filtered ratings were given first, when all items were rated under one parental filter before being rated with the other, or when the filter instruction was given only before the first four items (which refer to a relative or friend). These results do not support claims that reported imagery is generally dimmer under the father than under the mother filter, but it was suggested that dimmer father- than mother-filtered imagery for women may be an order effect or may appear when raters freely compare their images under the two filters. Because scores were highly correlated (rs > .80) across filters, it was concluded that the choice of a parent for the first four items of Marks' VVIQ does not jeopardize the use of the inventory as a research instrument to classify people as good or poor visualizers. PMID- 7991317 TI - Social correlates of the percentage of suicides and homicides employing firearms. PMID- 7991318 TI - Magnitude of stress experienced by baseball and softball umpires. AB - This study surveyed 782 certified baseball and softball umpires from randomly chosen umpire associations in one state to assess how much stress they experienced while officiating. The mean stress score was between "very little" and "a moderate amount," although 4.5% of the respondents reported "quite a bit" or "a great deal" of stress. The mean stress score may have been attenuated by the umpires' reluctance to admit stressful experiences or by collection of data after the season was over. PMID- 7991319 TI - Assessment of cognitive appraisal and coping linkages using two forms of canonical correlation. AB - As a conceptual framework for research on stress and coping, the transactional model of Lazarus and Folkman is process-oriented and requires methodologies that capture the process nature of cognitive appraisal and coping across stages of a transaction. Two forms of canonical correlation were used to analyze strength of association measures between pairs of cognitive appraisal and coping variable sets for 138 student subjects. Analysis indicated that, when an environmental transaction includes more than one time period, the generalized canonical correlation approach may offer some advantages in assessing linkage strength over the pairwise method. PMID- 7991320 TI - Hedonic ratings of odors as a function of odor sequence in older adults. AB - Pleasant and unpleasant odors were presented to 20 subjects in two same-valence blocks, i.e., all pleasant ones first, all unpleasant ones second, or vice versa, and in alternation. Hedonic ratings increased for the second block of odors which followed the first block of oppositely valenced odors. Alternation did not appear to affect hedonic ratings. These findings suggest that presentation of odors can alter hedonic ratings, producing a contrast effect when odors are given in a blocked fashion. PMID- 7991321 TI - The AAMD Adaptive Behavior Scale--School Edition, Part Two: Test-retest reliability and parent-teacher agreement in a behavior disordered sample. AB - Test-retest reliability and parent-teacher agreement were estimated for Part Two of the AAMD Adaptive Behavior Scale--School Edition. Test-retest reliability was based on a subgroup of 20 students selected randomly from the total sample of 66; these were 7 students classified as Behavior Disordered, 7 students referred for behavior problems but not classified, and 6 students not referred or classified. Parent-teacher agreement was investigated for a subgroup of 25 students classified as Behavior Disordered. Test-retest reliability of .83 was significant, while parent-teacher agreement coefficients were nonsignificant. Such results are consistent with previous research using similar instruments. The implications are discussed and suggestions for research are presented. PMID- 7991322 TI - Perceived importance of self-determination factors by consumers in substance abuse treatment. AB - 40 consumers (20 from 1993 and 20 from 1994) were randomly selected from about 450 residents of a midwestern urban free-standing residential substance-abuse treatment facility to participate in a study on factors relating to self determination. Self-confidence, positive attitude, listening skills, and assuming responsibility were identified in both years as the most important factors. Role models, however, were not reported as being important. PMID- 7991323 TI - The subjective meaning of good sleep, an intraindividual approach using the Karolinska Sleep Diary. AB - The present experiment used an intraindividual design to investigate the meaning and measurement of "good sleep". Each of 16 subjects slept in an isolation unit according to a schedule (15 sleeps) designed to give variable quality of sleep. Self-rated sleep measures (from the Karolinska Sleep Diary) were obtained after each sleep and subjected to intraindividual regression analyses across time. Most subjective sleep measures showed a strong covariation across conditions. Subjective quality of sleep mainly involved variables of sleep continuity, in particular, perceived calmness of sleep and sleep efficiency. "Sleep quality," "calm sleep," "ease of falling asleep," and ability to "sleep throughout" the time allotted strongly covaried and formed an index of sleep quality. Self-rated ease of awakening deviated from the general pattern and was associated with poor sleep quality. So was reported dreaming (related to awakenings). It was concluded that most subjective sleep measures tend to covary across conditions and that "good sleep" is mainly a question of sleep continuity. PMID- 7991324 TI - The Motor Activity Anxiety Test. AB - Feelings and perceptions of insecurity, anxiety, and danger can hinder motor learning and performance. The Motor Activity Anxiety Test is proposed to assess personal attitude to meet typical motor requirements for physical education in schools and anxiety about the physical dangers linked to motor activities in particular. The test is composed of 16 pictures and has been given to 1110 subjects ranging from 11 to 19 years of age. The test has good reliability and discriminative power. Previous research shows correlation between test scores and those on other psychological and motor tests. It is easy to complete in about 5 minutes. Teachers can use the information about their pupils to plan adequate strategies and help subjects overcome inhibitions and difficulties. Influences of gender, age, and experience on pupils' attitudes toward potentially dangerous sports and motor tasks might be studied through research. PMID- 7991325 TI - The critical mass hypothesis of suicide in adolescents. PMID- 7991326 TI - Shifting attention in a rapid visual search paradigm. AB - A method is introduced for studying shifts of attention in semantic space, testing 56 subjects in four experiments on a semantic monitoring task based on rapid, serial, visually presented (RSVP) word-sequences. Following a cue to shift attention, accuracy of semantic monitoring drops abruptly to a low level, then gradually recovers to reach preshift levels over successive stimuli in the RSVP sequence. Using this method, we compared two kinds of criterion-shifts, one requiring a set-reversal ('reversal shifts'), the other involving a shift between orthogonally defined categories ('orthogonal shifts'); no differences were found. We have also examined the difference in a shift between two different processing domains (semantic vs typographic) compared with a shift of criterion within the same processing domain. The results showed no differences for within- vs between domain shifts. Finally, we studied the time-course of a semantic attention shift. Execution of a semantic shift did not follow an internally controlled time-course but was a direct function of the rate of stimulus presentation. No evidence was found for the operation of a 'supervisory attentional system' independent of external stimulus triggering. PMID- 7991327 TI - Time spent with child and parental agreement about preschool children's behavior. AB - Although there is a common core of agreement in parental perceptions of their preschool-age sons' problem behavior, perceptions of 107 parents became more concordant as fathers increased the amount of time they spent with their sons. At least within the context of a sample who were at risk for developing abuse of alcohol or other substances and antisocial behavior, fathers who spent less time with their sons perceived them to be less troubled than mothers perceived them to be. PMID- 7991328 TI - Effects of a common linguistic misrepresentation on judgments about the relationship between height and weight. AB - Researchers have debated whether laypeople can detect covariation and have tried to identify conditions that might facilitate or retard this ability. Language, especially linguistic representation of variables, seems important to consider since misrepresentation appears to be relatively common in linguistic exchanges. In the present theory-based experiment, 16 subjects were asked to make judgments about the relationship between height and either weight (heavy or light) or bodyfat (fat or thin). Data provided evidence of a powerful illusory association, that is, if tall, then thin; if short, then fat, and there was no compelling evidence to suggest that subjects understood the relationship between height and weight. PMID- 7991330 TI - The sensed presence may be facilitated by interhemispheric intercalation: relative efficacy of the Mind's Eye, Hemi-Sync Tape, and bilateral temporal magnetic field stimulation. AB - After sitting quietly within an acoustic chamber, 30 university men were exposed (singly) to binaural, complex stimulation (Hemi-Sync Tape), synchronized binaural and visual patterns (The Mind's Eye), or transtemporal magnetic fields for 30 min. Experiences were rated at the end of the treatment by questionnaire. The men who received the binaural stimulation (Hemi-Sync Tape) reported more intense sensed presences and ego-alien intrusions than did the other two groups. In a similar second experiment, 18 university women who received the binaural stimulation also reported these experiences. The results support the hypothesis that the sensed presence is facilitated by transient, neuroelectrical intercalation of the temporoparietal lobes and is associated with the intrusion into awareness of the right-hemispheric equivalent of the left-hemispheric sense of self. PMID- 7991329 TI - Orthographic, phonologic, and semantic processing in reading disabled and nondisabled subjects. AB - In this study the confusability paradigm of Byrne and Shea and Waterman and Lewandowski was modified to include an orthographic condition made possible by presenting stimuli visually rather than aurally. The confusability tasks included a pseudoword-recognition task with only phonologic and orthographic information available for coding and a word-recognition task with phonologic, semantic, and orthographic information available for coding. 20 poor and 20 good readers (13 to 18 years of age) were asked to report whether stimuli had been presented a second time in two continuous lists (pseudoword and word). In contrast to previous work, phonologic confusability was not observed for either group, whereas orthographic confusability was noted for both groups on both tasks. Semantic confusability occurred for both groups on the word task. On these tasks which triggered orthographic and semantic processing (errors) poor readers performed comparably to good readers, suggesting that on a confusability task presented visually they were not disadvantaged. PMID- 7991331 TI - Intellectually gifted elementary students' perceptions of leadership. AB - To study the self-perceptions of leadership held by intellectually gifted elementary students in Grades 4 through 6 the Leadership Strengths Indicator was administered to 21 girls and 13 boys. Significant differences favoring the girls were found on two of the cluster scales (V, Sympathetic and VII, Conscientious) and the total score. PMID- 7991332 TI - Note on the definition and ethics of projective tests. AB - It is suggested that the definition of projective tests as assessment procedures which use ambiguous figures does not differentiate them from other procedures; and, to the extent that such a definition does differentiate, it describes a procedure that is inconsistent with current standards of ethical practice. An alternative definition, emphasizing the wide number of scorable responses elicited, is more ethical and serves to establish the relation of responses to projective test structure to psychometric tests through the more scientific bandwidth-fidelity issue of psychological assessment. PMID- 7991333 TI - Procedure for assessing verbal working memory in normal school-age children: some preliminary data. AB - A procedure for assessing children's recall of lexical items in the presence of a competing language task is described. The Competing Language Processing Task was designed to reflect the dynamic processes carried out in working memory during language comprehension and production by requiring that the subject hold words in temporary storage while analyzing and responding as true or false to statements. The development of the procedure is described and results of testing of 68 normal children ages 6, 8, 10, and 12 years are presented. PMID- 7991334 TI - Suicide by jumping in Singapore as a function of high-rise apartment availability. PMID- 7991335 TI - Illegal blood alcohol levels and traffic death rates. PMID- 7991336 TI - Covert orienting of attention controls vigilance decrement at low event rate. AB - Factors controlling sustained visual orienting were investigated by combining the paradigms of covert orienting and vigilance. Analysis suggests a close relationship between orienting of attention and vigilance which is dependent on the event rate during the vigilance task. At a low event rate both facilitatory and inhibitory effects of orienting are found. Vigilance decrement is related to the accumulation of inhibition over time, supporting Posner, et als 1984 theory. Invalid cues reduce the decrement. At a high event rate, however, neither facilitation nor inhibition effects are reliable, and vigilance decrement is related to limitations of the allocation of attentional capacity, supporting Parasuraman's multifactorial theory. The results suggest that facilitation and inhibition caused by orienting are important opposing mechanisms in visual attention, allowing the nervous system to control the distribution of attention both over visual space and over time. PMID- 7991338 TI - Field sobriety tests: are they designed for failure? AB - Field sobriety tests have been used by law enforcement officers to identify alcohol-impaired drivers. Yet in 1981 Tharp, Burns, and Moskowitz found that 32% of individuals in a laboratory setting who were judged to have an alcohol level above the legal limit actually were below the level. In this study, two groups of seven law enforcement officers each viewed videotapes of 21 sober individuals performing a variety of field sobriety tests or normal-abilities tests, e.g., reciting one's address and phone number or walking in a normal manner. Officers judged a significantly larger number of the individuals as impaired when they performed the field sobriety tests than when they performed the normal-abilities tests. The need to reevaluate the predictive validity of field sobriety tests is discussed. PMID- 7991337 TI - Alterations in pleasantness but not activation when long-term memories are reconstructed during contextual versus noncontextual settings. AB - Because the dorsomedial thalamus is a major input to the prefrontal cortices, the reconstruction of experience (episodic memory) that is maximally dependent upon this subcortical structure should be influenced by one of its major correlates, hedonistic tone. University men and women (ns = 20) were shown two brief video tapes of muricide and copulation among male rats during a lecture concerning instinctual behaviors. Two weeks later the subjects were asked to recall (written narratives) all of the details of the videotapes when they were in either the same or a different context. Although both groups generated similar numbers of words and employed words with comparable activation scores, the group who reconstructed the experiences outside of the context used words with significantly lower (eta = 0.59) pleasantness scores relative to the group who remembered the videotapes within the same setting. PMID- 7991340 TI - A computational examination of image segmentation and the initial stages of human vision. AB - A novel approach to the question of image segmentation is considered. Instead of relying on edge-detection mechanisms to encircle the image of an object, it is proposed that the general Gestalt-like properties of images of objects can be used. These manifest themselves as particularly simple properties at relatively coarse spatial scales when the image is filtered with orientation-selective filters. The first part of the paper is concerned with a computational analysis of this proposal. A key issue is the question of how the information in filtered images is extracted. A simple primitive parametric description of zero-bounded blobs is used in this paper. It is shown how such a scheme can support readily the clustering of features with Gestalt-like properties. In the second part of the paper, two general difficulties for vision that are particularly severe for the present scheme are considered. The first of these are the effects of strongly asymmetric illumination. The second are the effects of using a cluttered scene. In each case the nature of the problem is examined and the nature of the computational solution considered. PMID- 7991339 TI - Perceptual organisation and object recognition--POOR is the acronym, rich the notion. AB - Instead of studying perceptual organisation and object recognition in relative isolation, they can be viewed as two highly related sets of processes performed by the visual system to achieve its goal of acquiring information about the world. Fifteen papers devoted to specific subproblems within this active area of research have been brought together in two successive issues of Perception. Collectively they demonstrate that focusing on the functional interrelationships between perceptual organisation and object recognition will enrich our understanding of each of the subprocesses involved. The editorial provides an overview of the papers together with a discussion on how they relate to one another. If a general message is to be extracted from this set of papers, it is that the reported findings and the speculations offered to explain them suggest that the visual system's processes cannot be characterised in general by simple dichotomies such as analytic versus wholistic, bottom-up versus top-down, local versus global, low-level versus high-level, parallel versus serial, etc. Instead, it appears that a wide variety of mechanisms is available to the visual system. Therefore, a complete understanding of its functioning will require careful examination of the circumstances within which one processing mechanism seems to be selected over another, depending on the available information, the task demands, and perhaps even the observer's individual characteristics. PMID- 7991341 TI - The computation of contour information in complex objects. AB - Perceptual organisation, and especially the computation of contour information, has been the object of considerable interest in the last few years. In the first part of the paper we review recent accounts on the mechanisms involved in the processing of contour. In the second part we report an experiment designed to examine (1) how physical parameters such as spatial proximity and collinearity of elements affect the integration of global contour in objects and (2) whether the activation of stored representations of objects facilitates the computation of contour. Incomplete forms varying in the spacing and the alignment of line segments on their contour were used as stimuli in a matching task. Subjects were asked to decide which of two laterally displayed figures matched a reference form presented previously. The matching target and the distractor were physically identical but differed in their orientation. In one condition the reference object was always an outline drawing of an object. In a second condition the reference object was either a complete object or a more or less identifiable incomplete form. Little variation in performance was found for forms having continuous and discontinuous contour up to a spacing of 5 pixels (10.8 min) between elements. Response times and errors increased abruptly beyond this limit. This effect occurred in the two conditions of reference stimulus, suggesting that the computation of contour information is more affected by physical constraints at early processes than by high-level processes involving activation of stored structural representations of objects. PMID- 7991342 TI - Human pattern recognition: parallel processing and perceptual learning. AB - A new theory of visual object recognition by Poggio et al that is based on multidimensional interpolation between stored templates requires fast, stimulus specific learning in the visual cortex. Indeed, performance in a number of perceptual tasks improves as a result of practice. We distinguish between two phases of learning a vernier-acuity task, a fast one that takes place within less than 20 min and a slow phase that continues over 10 h of training and probably beyond. The improvement is specific for relatively 'simple' features, such as the orientation of the stimulus presented during training, for the position in the visual field, and for the eye through which learning occurred. Some of these results are simulated by means of a computer model that relies on object recognition by multidimensional interpolation between stored templates. Orientation specificity of learning is also found in a jump-displacement task. In a manner parallel to the improvement in performance, cortical potentials evoked by the jump displacement tend to decrease in latency and to increase in amplitude as a result of training. The distribution of potentials over the brain changes significantly as a result of repeated exposure to the same stimulus. The results both of psychophysical and of electrophysiological experiments indicate that some form of perceptual learning might occur very early during cortical information processing. The hypothesis that vernier breaks are detected 'early' during pattern recognition is supported by the fact that reaction times for the detection of verniers depend hardly at all on the number of stimuli presented simultaneously. Hence, vernier breaks can be detected in parallel at different locations in the visual field, indicating that deviation from straightness is an elementary feature for visual pattern recognition in humans that is detected at an early stage of pattern recognition. Several results obtained during the last few years are reviewed, some new results are presented, and all these results are discussed with regard to their implications for models of pattern recognition. PMID- 7991343 TI - Endogenous and exogenous control of visual selection. AB - Among the most fundamental issues of visual attention research is the extent to which visual selection is controlled by properties of the stimulus or by the intentions, goals, and beliefs of the observer. Before selective attention operates, preattentive processes perform some basic analyses segmenting the visual field into functional perceptual units. The crucial question is whether the allocation of attention to these perceptual units is under the endogenous control of the observer (intentions, goals, beliefs) or under the exogenous control of attention in tasks in which subjects search for a particular 'basic' feature (eg search for a unique colour, shape, or brightness). In the present review it is suggested that selectivity in these types of search tasks is dependent on the relative saliency of the stimulus attributes. It is concluded that the visual system automatically calculates differences in basic features (eg difference in shape, colour, or brightness) and that visual information occupying the position of the highest saliency across stimulus dimensions is exogenously passed on to the 'central presentation' that is responsible for further stimulus analysis. Alternative explanations of the present findings and tentative speculations resulting from the present approach are discussed. PMID- 7991344 TI - Effects of attention on perception of features and figural organisation. AB - Four studies are reported that demonstrate effects of attention on early perceptual processes. These studies show that directing attention to stimulus location influences perceived brightness, perceived length, and the overall organisation of the Muller-Lyer figure and ambiguous figures. Since in all four studies the dependent measure was dissociated from the attentional instructions, the results are not open to traditional criticism of late-selection advocates, and therefore provide strong support for early-selection views of attention. PMID- 7991345 TI - Parallel visual coding in three dimensions. AB - Evidence from visual-search experiments is discussed that indicates that there is spatially parallel encoding based on three-dimensional (3-D) spatial relations between complex image features. In one paradigm, subjects had to detect an odd part of cube-like figures, formed by grouping of corner junctions. Performance with cube-like figures was unaffected by the number of corner junctions present, though performance was affected when the corners did not configure into a cube. It is suggested from the data that junctions can be grouped to form 3-D shapes in a spatially parallel manner. Further, performance with cube-like figures was more robust to noncollinearity between junctions than was performance when junctions grouped to form two-dimensional planes. In the second paradigm, subjects searched for targets defined by their size. Performance was affected by a size illusion, induced by linear-perspective cues from local background neighbourhoods. Search was made more efficient when the size illusion was consistent with the real size difference between targets and nontargets, and it was made less efficient when the size illusion was inconsistent with the real size difference. This last result occurred even though search was little affected by the display size in a control condition. We suggest that early, parallel visual processes are influenced by 3-D spatial relations between visual elements, that grouping based on 3-D spatial relations is relatively robust to noncollinearity between junctions, and that, at least in some circumstances, 3-D relations dominate those coded in two-dimensions. PMID- 7991346 TI - Visual separability: a study on unschooled adults. AB - It has been suggested in previous studies that unschooled adults present serious difficulties at performing tasks which, like part verification, dimensional filtering, or orientation judgments, require them to pay attention to a specific aspect of the stimulus structure. In the present study we examined the performance of unschooled adults by using a task which does not explicitly require the subjects to attend selectively to a specific component of the stimuli. Separability either of parts or of dimensions as well as line orientation registration were estimated by the occurrence of illusory conjunctions. Whatever the properties involved in the illusions, these occurred in unschooled adults, at about the same rate as in age-matched schooled controls. The two sets of contrasting findings suggest that a critical variable is whether or not the subjects' attentional control is required. The relevance of the present findings as regards the level of processing responsible for illusory conjunctions is discussed. PMID- 7991347 TI - Familiarity and pop-out in visual search. AB - In this paper, we report that when the low-level features of targets and distractors are held constant, visual search performance can be strongly influenced by familiarity. In the first condition, a [symbol: see text] was the target amid [symbol: see text]s as distractors, and vice versa. The response time increased steeply as a function of number of distractors (82 msec/item). When the same stimuli were rotated by 90 degrees (the second condition), however, they became familiar patterns--2 and 5--and gave rise to much shallower search functions (31 msec/item). In the third condition, when the search was for a familiar target, N (or Z), among unfamiliar distractors, [symbol: see text]s (or [symbol: see text]s), the slope was about 46 msec/item. In the last condition, when the search was for an unfamiliar target, [symbol: see text] (or [symbol: see text]), among familiar distractors, Ns (or Zs), parallel search functions were found with a slope of about 1.5 msec/item. These results show that familiarity speeds visual search and that it does so principally when the distractors, not the targets, are familiar. PMID- 7991349 TI - On apparent misalignment of collinear edges and boundaries. AB - In two experiments, subjects adjusted various pairings of the top and bottom boundaries of two obliquely oriented outline bars (Experiment 1) and those of two similarly oriented complete and incomplete squares (Experiment 2) to apparent alignment. The data from the first experiment showed that the misalignment effects were determined jointly by the directional properties of the bar ends (vertical, oblique, and semicircular) and the pair of boundaries that were aligned (both top boundaries, top of upper bar with bottom of lower bar, bottom of upper bar with top of lower bar). The results from the second experiment showed that the misalignment effects were the same for the oblique boundaries of solid and outline squares and persisted when the squares were reduced to two parallel lines. The effect was undiminished when the ends of the parallels were aligned, but was markedly reduced when pairs of parallels themselves were aligned. The outcomes of the two experiments are explained in terms of the apparent positions of the oblique boundaries. It is proposed that these vary with the positions of the elements (bar or square) relative to the visual field, the position of the boundaries relative to the stimulus elements, and the positions of the boundaries relative to axes that are delineated by the parallel adjacent ends of bars and sides of squares. This relative-position basis for apparent misalignment is held to be the basis of misalignment effects in other figures. PMID- 7991348 TI - Signal clustering modulates auditory cortical activity in humans. AB - Auditory streaming and its relevance to attentional processing was examined using event-related brain potentials (ERPs) in situations facilitating perception of one or two streams of sounds. Subjects listened to sequences of brief tones of three different frequencies presented in random order. In evenly spaced (ES) conditions, the three frequencies were equidistant on the musical scale. In clustered, easy (CE) conditions, the attended frequency was distinct, while the middle and extreme distractor tones were clustered together. In clustered, hard (CH) conditions, the attended frequency was clustered with one of the distractors. The subjects pressed a button in response to occasional target tones of longer duration at a prespecified frequency. The subjects were faster and more accurate in CE conditions than they were in ES conditions, and ERP attention effects were enhanced in amplitude in CE conditions. Conversely, the subjects were slower and less accurate in CH conditions and ERP attention effects were delayed in latency and decreased in amplitude. Clustering effects suggest that the processing of stimuli belonging to the attended stream was promoted and the processing of those falling outside the stream was inhibited. The timing and scalp distribution of clustering-related changes in ERPs suggest that clustering modulates early sensory processing in auditory cortex. PMID- 7991350 TI - Stimulus exposure time and perceptual memory. AB - The recent explosion of research on implicit memory has facilitated the examination of perceptual and conceptual processes in the encoding of information. Nevertheless, stimulus exposure time--the amount of time that a stimulus is physically available to a perceiver's scrutiny--has received little attention. In the present paper, we examine the effect of stimulus exposure time on three implicit memory measures (word-fragment completion, perceptual identification, and general knowledge) and two explicit memory measures (graphemic cued recall and semantic cued recall). In Experiment 1, we demonstrated that increases in exposure time lead to increases in implicit perceptual memory, but not to implicit conceptual memory, when the encoding task focuses on perceptual features of the stimulus. We replicated this effect in Experiment 2 and demonstrated that increases in exposure time lead to increases in perceptual and conceptual memory when the measures are explicit. Thus, the current experiments demonstrate that manipulations of exposure time lead to dissociations in implicit, but not explicit, memory. PMID- 7991351 TI - Selective attentional delays and attentional capture among simultaneous visual onset elements. AB - Visual discrimination and detection responses to a single stimulus presented simultaneously with noise stimuli are slower and less accurate than are responses to a single stimulus presented alone. This occurs even though the location of the relevant stimulus (target) is known or visually indicated with stimuli onset. Results showed that noise elements delay focal attending and processing of a target. Furthermore, precuing the target location reduces, and can eliminate, target processing delays. Processing delays were not due to response competition or to random attentional capture by noise. It is suggested that simultaneous stimuli are perceived initially as a single object, and delays in processing a single stimulus are due to difficulties in perceptually segregating this stimulus from noise. Precuing is assumed to facilitate this segregation process. PMID- 7991353 TI - Interference and negative priming from ignored distractors: the role of selection difficulty. AB - The relation between distractor interference and negative priming from identical distractors was examined in two experiments. Subjects responded to a target letter, which was indicated by an adjacent bar marker, and attempted to ignore a distracting letter. On prime trials, distracting letters were either compatible or incompatible with the target, allowing for a measure of interference. On subsequent probe trials, previously ignored distractors were sometimes presented as targets, allowing for a measure of negative priming. Reducing the spatial separation between targets and distractors on the prime trial increased the magnitude of interference and negative priming, but these effects appeared to be independent of each other (Experiment 1). In Experiment 2, the prime target location was precued on some trials, but not on others. Precuing attenuated the magnitude of interference, but not that of negative priming effects. This pattern indicates that measures of negative priming and measures of distractor interference on the immediately preceding trial are independent. The results are discussed in terms of a selective inhibition model of selective attention. PMID- 7991352 TI - Object recognition contributions to figure-ground organization: operations on outlines and subjective contours. AB - In previous research, replicated here, we found that some object recognition processes influence figure-ground organization. We have proposed that these object recognition processes operate on edges (or contours) detected early in visual processing, rather than on regions. Consistent with this proposal, influences from object recognition on figure-ground organization were previously observed in both pictures and stereograms depicting regions of different luminance, but not in random-dot stereograms, where edges arise late in processing (Peterson & Gibson, 1993). In the present experiments, we examined whether or not two other types of contours--outlines and subjective contours- enable object recognition influences on figure-ground organization. For both types of contours we observed a pattern of effects similar to that originally obtained with luminance edges. The results of these experiments are valuable for distinguishing between alternative views of the mechanisms mediating object recognition influences on figure-ground organization. In addition, in both Experiments 1 and 2, fixated regions were seen as figure longer than nonfixated regions, suggesting that fixation location must be included among the variables relevant to figure-ground organization. PMID- 7991354 TI - Classical geometric illusion effects with nonclassical stimuli: angular induction from decomposing lines into point arrays. AB - Angular induction is the process by which one line segment can bias judgment of orientation and/or collinearity of another segment, and it has been established that the magnitude of error is a determinate function of the relative angle between the two. We examined how these known relationships are affected by decomposing the induction segment into an array of scattered points. The bias that was produced by such arrays was found to be consistent with a formal model of angular induction, with the strength of the effect decreasing as the scatter among the points was increased. This decline in strength was almost linear with a logarithmic transform of the dimensions of the stimulus array. We also evaluated the hypothesis that the induction stimulus is detected by one or more channels- for example, neurons--for which the sensitivity profiles are modeled as Gabor wavelets. The change in induction strength with increasing point scatter was not predicted by a single width of channel. However, the combined activity of an ensemble of channels that differed in width did match the perceptual effects if one also stipulated that each channel would respond maximally to a fine-line stimulus. PMID- 7991355 TI - The gender-marking effect in spoken word recognition. AB - In this paper we examine whether the recognition of a spoken noun is affected by the gender marking--masculine or feminine--that is carried by a preceding word. In the first of two experiments, the gating paradigm was used to study the access of French nouns that were preceded by an appropriate gender marking, carried by an article, or preceded by no gender marking. In the second experiment, subjects were asked to make a lexical decision on the same material. A very strong facilitatory effect was found in both cases. The origin of the gender-marking effect is discussed, as well as the level of processing involved--lexical or syntactic. PMID- 7991356 TI - Stereoscopic perception with brief exposures. AB - In this report we describe the results of an experiment in which we demonstrated that a powerful and compelling stereoscopic experience is elicited with very brief (< 1 msec) stimulus durations. The observers were highly successful in recognizing briefly flashed, stereoscopic, random-dot surfaces in the absence of monocular contours. The results are shown to be closely related to the range of depths for any stimulus form; however, the recognition thresholds were nonmonotonic as a function of disparity. Previous investigators have disagreed about the existence of a temporal threshold for stereopsis. We believe that prior findings suggesting that stereopsis cannot occur at short exposure durations are probably due to inadequate control of fixation disparity. Therefore, there is poor dichoptic image registration when a stereoscopic stimulus is presented. The present results also raise difficulties for any theory of stereopsis that requires eye movements. PMID- 7991358 TI - Abstracts of the joint meeting of the German Physiology Society 73rd meeting. 2-5 March 1994, Jena. PMID- 7991357 TI - Adaptation effects and reversible figures: a comment on Horlitz and O'Leary. AB - Horlitz and O'Leary have provided further evidence for the important role of such top-down processes as attention and familiarity on reported reversals of ambiguous figures. As such, these results are consistent with the claims of several other investigators who have argued that any theory of phenomenal reversal that is based solely on passive neural processes is likely to be incomplete. However, Horlitz and O'Leary make the additional claims (1) that the several reports of adaptation effects in the literature are readily reinterpreted within an information-access framework and (2) that their own empirical work demonstrates a basic failure of neural-adaptation effects with reversible figures. It is proposed here that these claims must be viewed with caution. First, Horlitz and O'Leary's explanation for the discrepancy of their results from those of ostensibly similar experimental procedures in the reversible-figure literature is not the only, or the most likely, possibility. A plausible alternative model that posits critical procedural differences (specifically, duration of adaptation) across studies has been offered, and supporting empirical work for this latter suggestion has been presented. Second, the empirical efforts of Horlitz and O'Leary, while providing further evidence for top-down processes, do not eliminate the likely role of adaptation effects with reversible figures. There is strong reason to believe that the viewing conditions selected by these researchers may not have been sufficient to produce appreciable adaptation. Moreover, there is excellent reason to believe that both bottom-up and top-down processes moderate reported reversals of these figures.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7991359 TI - Amputation and reflex sympathetic dystrophy. AB - Reflex sympathetic dystrophy is a chronic pain syndrome characterized by chronic burning pain, restricted range of motion, oedema and vasolability. Patients are difficult to treat and the prognosis is very often poor. This report emphasizes that an amputation in case of a reflex sympathetic dystrophy is mostly due to a too late recognition of this syndrome. In the international literature little is written about an amputation as a therapy for reflex sympathetic dystrophy. It is only mentioned as a therapy in the end stages of this syndrome. Sometimes a rejected amputation, as in this case report, can have a relatively good result. An early recognition of this pain syndrome produces the best possible outcome. PMID- 7991360 TI - A CAD analysis programme for prosthetics and orthotics. AB - A CAD (computer aided design) analysis software package (CADVIEW) was designed for use with prosthetic and orthotic CAD CAM (computer aided design/computer aided manufacture) systems. Using the Microsoft Windows 3.1 environment, CADVIEW provides a series of anatomical shape viewing and analysis tools. These tools include simultaneous display of multiple sockets and multiple views, two dimensional (2D) and three dimensional (3D) measurement, shape statistics, multi shape alignment, cross-sectional comparison, colour coded 3D comparison, resolution enhancement, and image copying capabilities. This programme should be of benefit to clinicians and researchers who wish to assess and/or compare CAD data generated by MS-DOS based CAD CAM systems. PMID- 7991361 TI - A body powered prehensor with variable mechanical advantage. AB - The purpose of this research was to improve body powered, voluntary closing (VC) prosthetic prehension. A prototype prehensor with variable mechanical advantage was fabricated and tested. The device operates at low mechanical advantage during sizing of an object to reduce cable excursion requirements. It shifts to high mechanical advantage during gripping to allow high prehensile forces to be generated with reduced cable tension. The prototype provides a mechanical advantage of 2.4, nearly five times that of conventional VC devices. The prototype also acts as a holding assist; after grip forces are applied, they can be maintained with a cable tension of only 3 lb (13.34N). Field testing indicated that the device performs well in many tasks. The mechanism allows greater range of motion while an object is grasped than standard voluntary closing prehensors. However, the device performed poorly in grasping very compliant objects. To address this problem, a switch has been incorporated into the prototype to allow it to be used in a free-wheel mode. PMID- 7991362 TI - Re: "Fatigue testing of energy storing prosthetic feet", pp 180-188, volume 17, 1993. PMID- 7991363 TI - Gait in male trans-tibial amputees: a comparative study with healthy subjects in relation to walking speed. AB - Walking speed, stance duration and ground reaction forces were studied with the use of a stable force platform (Kistler) in 24 male transtibial amputees and 12 healthy subjects matched for sex and age. The aim of the study was to compare the gait performance of two groups with unilateral trans-tibial amputations for either vascular disease or trauma and also to compare the results of the two groups with the results of a group of healthy subjects. Multiple linear regression analysis was used to compare the stance duration and the ground reaction forces in relation to walking speed. The vascular and traumatic amputees had significantly reduced walking speeds compared with the healthy subjects, 0.85 +/- 0.2 m/s and 0.99 +/- 0.2 m/s. respectively, as compared to 1.42 +/- 0.2 m/s. By comparing the vascular and traumatic amputees with the healthy subjects in relation to walking speed, it was shown that the gait performance of the vascular amputee differed from that of the traumatic amputee, a difference that was not caused by the reduced walking speed. The active forces during push off on both the healthy (p = 0.02) and the prosthetic leg (p = 0.003) in the trauma group were not found in the vascular group. This disparity could be an effect of the systemic disease. It may be argued that the results of this study contribute to the understanding of the reduced walking ability of the vascular amputee and should be borne in mind when planning rehabilitation. PMID- 7991364 TI - Experiences with respect to the ICEROSS system for trans-tibial prostheses. AB - This article describes the authors' initial experiences and those of their patients with respect to the ICEROSS system for trans-tibial prostheses. Up to October 1992, 54 patients attending the "Hoensbroeck" Rehabilitation Centre received such a prosthesis. With the aid of patients' records an all-round evaluation has been made. In addition, a survey was undertaken and an examination made amongst the 43 patients who responded to a written request. For 26 patients who were provided with the ICEROSS as a second appliance after having used an older kind of prosthesis a comparison was made with the old system. In general these patients considered the new prosthesis as providing a clear improvement. PMID- 7991365 TI - Energy expenditure of trans-tibial amputees during ambulation at self-selected pace. AB - The purpose of this investigation was two-fold: 1) to compare the metabolic cost (VO2), heart rate (HR), and self-selected speed of ambulation of trans-tibial amputees (TTAs) with those of non-amputee subjects; and 2) to determine whether a correlation exists between either stump length or prosthesis mass and the energy cost of ambulation at the self-selected ambulation pace of TTAs. Subjects were thirty-nine healthy male non-vascular TTAs between the ages of 22 and 75 years (mean +/- sd = 47 +/- 16). All had regularly used their prosthesis for longer than six months and were independent of assistive ambulation devices. Twenty-one healthy non-amputee males aged 27-47 years (31 +/- 6) served as controls. Subjects ambulated at a self-selected pace over an indoor course, with steady state VO2, HR, and ambulation speed averaged across minutes seven, eight and nine of walking. Results showed that HR and VO2 for TTAs were 16% greater, and the ambulation pace 11% slower than the non-amputee controls. Significant correlations were not observed between stump length or prosthesis mass, and the energy cost of ambulation. However, when the TTA subject pool was stratified on the basis of long and short stump length, the former sustained significantly lower steady-state VO2 and HR than the latter while walking at comparable pace. These data indicate that stump length may influence the metabolic cost of ambulation in TTAs. PMID- 7991366 TI - Subjective benefits of energy storing prostheses. AB - The energy storing (ES) prosthesis has been used in the Prosthetic Foundation's workshop since 1987. Subjective responses from 168 amputees (141 trans-tibial and 27 trans-femoral) fitted with the ES prosthesis were analysed. Ratings were generally favourable in comparison with those for conventional prostheses. The most pronounced advantages of the new prosthesis as shown by the ratings were in walking uphill or swift walking. The younger amputees had more benefit than the older ones. High body weight decreased the benefit of the ES prosthesis. The ES prosthesis does not seem to provide any major advantage for the less active amputee whose movements are mainly indoors. PMID- 7991367 TI - A new modular six-bar linkage trans-femoral prosthesis for walking and squatting. AB - Four-bar linkage mechanisms produced by many designers of knee joints for trans femoral prostheses can provide knee rotation to permit walking only. In Afro Asian countries people are accustomed to a squatting posture in their daily activities. A six-bar linkage knee-ankle mechanism trans-femoral prosthesis is described which was developed and fitted to an amputee. The motion patterns of the ankle, knee and thigh during walking and squatting (obtained using a flickering light emitting diode system) for the above prosthesis is compared with motion patterns obtained for normal subjects. The closeness between both the patterns establishes the suitability of the new modular trans-femoral prosthesis for producing near normal patterns of motion during walking and squatting. The additional facility of cross-legged sitting provided in the prosthesis makes it functionally suitable for Afro-Asian amputees. PMID- 7991369 TI - Caught on camera. PMID- 7991368 TI - Promoting continence. Part II. The role of the nurse. PMID- 7991370 TI - A fresh start. PMID- 7991371 TI - Storm on the Clyde. PMID- 7991372 TI - Taken on trust. PMID- 7991373 TI - Treatment for infertility: counting the cost. AB - This paper looks at the provision of infertility treatment in the UK. In August this year the College of Health reported on the funding and provision of fertility services and found that local variations in access to services still exist. PMID- 7991374 TI - Continuity of care in IVF: the nurse's role. AB - In this paper the author explains the process of in vitro fertilisation. She outlines the nurse's role in patient consultation and counselling at her unit in Oxford and the importance of that role in ensuring continuity of care. PMID- 7991375 TI - Full steam ahead. PMID- 7991376 TI - Systems of life. Blood: 6. PMID- 7991377 TI - Using patient biography to promote holistic care. AB - The value of patient biographies has become apparent over recent years, especially within the specialty of health care of older people. This paper describes how a nursing assistant built up a relationship with an older man in his ward, who had previously been seen as 'difficult', through a shared interest in music, and by getting the patient to tell him his life story. PMID- 7991378 TI - Forging links. PMID- 7991379 TI - Systems of immunity. PMID- 7991381 TI - Mental health. Coping with caring. PMID- 7991380 TI - Mental health. Medication clinics. PMID- 7991382 TI - Wound care. Risk reduction. PMID- 7991383 TI - Wound care. The ideal healing environment. PMID- 7991384 TI - Wound care. Dressing choices. PMID- 7991385 TI - Wound care. Assessment criteria. PMID- 7991386 TI - Promoting continence. Part III. Revision notes. PMID- 7991387 TI - A bloody transition. PMID- 7991388 TI - Beyond the screen. PMID- 7991389 TI - Reserve findings. PMID- 7991390 TI - Shared values. PMID- 7991391 TI - The power of one. PMID- 7991392 TI - The named nurse in accident and emergency departments. AB - The 'named nurse' concept was introduced to the public in 1991. This paper describes the thinking behind the introduction of named nurses into one A&E department, utilising a specific model of nursing. PMID- 7991393 TI - Advice over the telephone. AB - The authors of this paper anonymously telephoned A&E departments in the Thames area that provided 24-hour emergency cover to investigate the safety and validity of medical advice given by these departments over the telephone to the public. PMID- 7991394 TI - An attack on justice. PMID- 7991395 TI - Nutrition and pregnancy: problems and solutions. AB - There is no doubt that a healthy and well-nourished woman living in a comfortable environment is able to support the demands of pregnancy and lactation. She will also be able to protect her offspring against short periods of nutritional and environmental abuse. Good nutritional status in a woman of reproductive age before conception and during pregnancy is, therefore, of vital importance in the successful outcome of pregnancy in successive generations. This paper discusses the issues involved. PMID- 7991396 TI - Local anaesthesia in the operating theatre. AB - Cocaine was the first drug to be used as a local anaesthetic. It was introduced into medicine in 1884 by Koller. Other drugs soon followed, for example, ethyl chloride spray, tropocaine, eugenol (oil of cloves) and Nupercaine. A wide range of uses for local anaesthetics soon developed and the term 'regional anaesthesia' was first used by Cushing in 1901 to describe pain relief by nerve blockade. Local anaesthetic drugs are water soluble salts of lipid soluble alkaloids. Each molecule is composed of an aromatic portion, intermediate chain and an amide portion. The portions are joined by either amide or ester linkages. Ester-linked drugs are hydrolysed in the plasma by plasma cholinesterase and their half-life varies from one to eight minutes. Amide-linked drugs are degraded by oxidative dealkylation in the liver. The half-life of these drugs varies from 1.5 to more than three hours. The addition of a vasoconstrictor, such as adrenaline, will prolong the duration of action of both the amide- and ester-linked drugs. Degradation of the amide-linked drugs depends on factors such as hepatic blood flow and liver conditions, such as cirrhosis, and congestive cardiac failure. Anaphylactic reactions are more common with ester-linked drugs than amide-linked drugs. The drugs are usually available for injection as hydrochlorides in a salt solution with small amounts of fungicides or preservatives added to give stability. PMID- 7991397 TI - Labouring for status. PMID- 7991398 TI - Changing ideas. PMID- 7991399 TI - Internal customers. PMID- 7991400 TI - Benchmarking best practice. PMID- 7991401 TI - Pseudomonas infection. PMID- 7991402 TI - Hepatitis revisited. PMID- 7991404 TI - Psychologic adjustments to reconstructive surgery. AB - Reconstructive surgery carries with it both physical and psychologic manifestations. The plastic surgery nurse must be aware of the functional, physical, and psychologic needs of the patient. This article explores issues associated with body image and psychologic adjustment, as well as nursing intervention for the trauma patient, the patient who has suffered from disease leading to the necessity for reconstructive surgery, patients with congenital defects, and patients undergoing multi-staged reconstruction. PMID- 7991403 TI - Selection and preoperative preparation of plastic surgery patients. AB - There is no nursing specialty in which the marriage between physical and psychosocial care of the individual is so evident as in plastic surgery nursing. The patient's surgical outcome and adjustment to the body image change depend largely on nursing care. During the adjustment period, the patient is likely to confide in the nurse, and it is clear that the patient benefits from a knowledgeable and empathetic nurse. Nurses and patients have long recognized the value of nursing care in the treatment of the plastic surgery patient. As plastic surgery becomes more widespread in the next century, the unique skills of the plastic and reconstructive surgery nurse will be even more treasured. PMID- 7991405 TI - Methods of reconstruction. AB - This article discusses methods of reconstruction, ranging from simple free-hand skin grafts to microvascular tissue transfer. The simplest reconstructive option must be chosen to suit the defect and to achieve the least possible donor morbidity. The most suitable reconstructive choices are discussed for each of the following situations: to provide a large surface area, to provide hair-bearing tissue, to fill "dead space," to restore motor function, or to provide composite bone and soft-tissue structures. PMID- 7991406 TI - Facial rejuvenation. AB - Facial rejuvenation includes several operations: rhytidectomy, rhinoplasty, blepharoplasty, mentoplasty, brow lift, chemical face peel dermabrasion, and collagen injections. The nurse's role begins with identification of expectations of the procedure. The operations described take the surgeon a few hours. Yet the ultimate success occurs over the weeks of postoperative care. Because most operations are performed on outpatient basis, the nurse's role is crucial in preparing the patient for self-care. PMID- 7991407 TI - Body contouring surgery. AB - This article discusses nursing care of patients having body contouring surgery of the abdomen, thighs, and breasts. Specific surgery reviewed includes lipoplasty, abdominoplasty, thigh lift, breast reduction, and breast augmentation. PMID- 7991408 TI - Current concepts in breast reconstruction. AB - Breast cancer is the leading malignancy in women in the United States. Breast reconstruction is an important aspect in the treatment regime for breast cancer. Reconstruction now is a daily occurrence, providing women with a life-enhancing opportunity. Women contemplating reconstruction may choose from a broad menu of options allowing for tailored care. PMID- 7991409 TI - Traumatic injuries of the face and hands. AB - Trauma to the face and hands initiates a comprehensive and often long-term course of treatment and reconstruction. Evaluation of the injuries and accurate on-going nursing assessment of the patient is essential to obtain optimal results. This article discusses both functional decision-making and aesthetic concerns. PMID- 7991410 TI - Common pediatric craniofacial reconstructions. AB - The emphasis on beauty in our society also places demands on children to meet a certain appearance. With cleft lip and palate being one of the most common birth defects, it is likely that pediatric nurses or pediatric nurse practitioners will encounter children requiring a form of craniofacial surgery. This article discusses common reconstruction techniques and important features of care. PMID- 7991412 TI - Transcultural nursing. A personal and professional challenge. AB - The traveling nurse is a guest in the host country. It is wise to remember that we represent our country and our culture--we are the only Americans many of the locals have even seen. Be sure that foreigners see in us the very best example of American citizens. After work, there is often opportunity to spend time with the local people. They are usually extremely hospitable and anxious to share their culture. A nurse who can get involved with the local people has the chance to learn so much--different values, priorities, and customs. The culture may be rich in history and folklore. Their approach to health care can be fascinating--very different from our own, yet effective in many ways. There are often highly skilled craftsmen among the people are, producing wonderfully sophisticated things from nearly nothing. It is a source of real joy to bring back treasures from a culture one has come to know. In addition to the opportunity for clinical growth and the refinement of team skills, foreign travel provides an opportunity to grow personally. Adapting to new and more primitive surroundings requires patience and understanding. Interacting with people of a different culture also gives one the opportunity to evaluate ones own beliefs and attitudes. Sometimes it is surprising to realize that we are more snobbish or prejudiced than we believed; that revelation can be an opportunity for growth and change and a new source of pride in our country, our profession, and ourselves. PMID- 7991411 TI - Surgical management of pressure ulcers. AB - This article describes how debridement and dressings are used to clean wounds prior to closure with myocutaneous flaps. Post-operative care focuses on promoting flap perfusion, especially by reducing pressure on the flap and by promoting wound drainage. Rehabilitation of the patient is imperative to reduce recidivism. PMID- 7991413 TI - The plastic surgical nurse. Nurse specialist for the 1990s. AB - In the preface to the Core Curriculum, editor Terri Goodman, RN, MA, CPSN, CNOR, eloquently describes plastic surgical nursing as "a dynamic specialty that is expanding rapidly in response to technology, creativity, and the increasing autonomy of both nurse and patient." She goes on to say that today's "plastic surgical nurse [is] a sensitive, skilled communicator [possessing] a broad knowledge base and the ability to apply principle." These are exciting times in which to be a nurse. Yes, the winds of change are blowing. Some see them as threatening the core of medical practice, that is, caring for patients. Others see them bringing opportunity, empowerment for nurse specialists, and freedom to reach new levels of professionalism. The specialty of plastic surgical nursing is proud to be a part of this exciting future. PMID- 7991414 TI - Left heart function during right heart pacing. PMID- 7991415 TI - Troubleshooting implantable cardioverter defibrillator system malfunctions: the role of impedance measurements. AB - High impedance measurements may be used to troubleshoot ICD system malfunction. In four different cases a defective system was identified or confirmed by an abnormal impedance: two secondary to lead fractures, one to an adapter faulty connection, and one to a loose set-screw connection. This led to further diagnostic procedures that ultimately localized the difficulty. Though the problems with ICD may be of diverse origins, routine use of impedance measurement for the troubleshooting of these systems may serve as an early sign of malfunction and would point the need for further investigation. PMID- 7991416 TI - Effectiveness of noninvasive programmed stimulation for initiating ventricular tachyarrhythmias in patients with third-generation implantable cardioverter defibrillators. AB - Previous generations of implantable cardioverter defibrillators (ICDs) required invasive electrophysiological testing to assess defibrillator function. Newer third-generation ICDs include the capability for performing noninvasive programmed stimulation (NIPS) and may reduce the need for invasive studies to assess tachycardia recognition and antitachycardia therapy algorithms. The effectiveness of ICD-based NIPS for the induction of ventricular arrhythmias has not, however, been formally assessed. Third-generation ICDs were implanted in 79 patients, who underwent a total of 166 postoperative defibrillator tests. NIPS with rapid ventricular pacing was performed in all patients in an attempt to induce ventricular fibrillation. In patients with prior sustained uniform ventricular tachycardia, programmed stimulation with up to three extrastimuli was performed in order to attempt to initiate the clinical ventricular tachcardia. Ventricular fibrillation was induced with NIPS in 146 of 166 studies (88%). Ventricular tachycardia was initiated with NIPS in 104 of 123 studies (85%). The type of defibrillator and the use of endocardial or epicardial rate sensing/pacing leads did not influence the efficacy of NIPS. NIPS with third generation ICDs is generally effective at inducing ventricular fibrillation and clinically relevant ventricular tachycardias, and reduces the need to perform invasive electrophysiological testing following device implantation. In a minority of patients temporary transvenous pacing catheters must still be used to facilitate arrhythmia induction. PMID- 7991417 TI - Beat-to-beat behavior of QT interval during conducted supraventricular rhythm in the normal heart. AB - To assess beat-to-beat behavior of QT interval under different conditions, high resolution recordings and computerized beat-to-beat analysis of the electrocardiogram were performed at rest, during recovery after short exercise, and during atrial pacing. Beat-to-beat variations of QT interval during sinus rhythm at rest and after short exercise were measured in ten healthy men. In an additional three patients with supraventricular tachycardia, beat-to-beat QT changes were studied after abrupt sustained acceleration and deceleration of heart rate by atrial pacing. Beat-to-beat changes in RR interval at rest are followed by minimal changes of the QT interval. The measured proportional change of the QT interval compared with the change in RR interval (delta QT/delta RR) was 0.02. This value represents 10% of the value expected for QT changes from Bazett's formula. Following short exercise QT interval did not change for 15 seconds and reached a maximal value 80 seconds later as compared to the RR interval (192 vs 115 secs, P < 0.001). The steady state of the QT interval during sustained atrial pacing was achieved after 132, 135, and 133 seconds for pacing intervals of 600, 500, and 600 msec, respectively. Our data indicate a relatively slow adaptation of the QT interval to changes in heart rate. PMID- 7991418 TI - Correlation of the endocardial fragmented electrogram with body surface signal averaged electrocardiographic mapping. AB - We compared signal-averaged electrocardiography (SAE), SAE mapping, and left ventricular catheter mapping in 60 patients with ischemic heart disease. Using the data obtained in patients with no fragmented electrograms (FE) in the left ventricle, the late potential was defined by SAE as a filtered QRS duration > 131 msec or a root mean square voltage < 16 microV for the last 40 msec of the QRS complex. SAE mapping was performed by recording the signal-averaged electrocardiogram at 48 sites on the body surface. With SAE mapping, the filtered QRS duration and the area in the last 20 msec of the QRS complex were significantly different between the patients with and without FEs. The late potential was defined by SAE mapping as a filtered QRS duration > 136 msec or an area < 28 microV.msec for the last 20 msec of the QRS complex. The sensitivity and specificity of detecting FEs were 46% and 88%, respectively, by the SAE filtered QRS criterion, while they were 66% and 88% by the root mean square criterion. In contrast, SAE mapping gave values of 66% and 92% by the filtered QRS criterion, as well as values of 100% and 92% by the area criterion. Thus, SAE mapping provided better detection of the FE and was more closely correlated with the results of catheter mapping, suggesting its potential for clinical application. PMID- 7991419 TI - Predictors of device activation for ventricular arrhythmias and survival in patients with implantable pacemakers/defibrillators. CADENCE Investigators. AB - Predictors of survival and arrhythmia recurrence for patients with implanted defibrillators have been reported but patients with sustained, well-tolerated ventricular tachycardia were often excluded from these trials. Arrhythmia recurrence and survival in populations including these patients have been less well studied. The purpose of the present study was to examine predictors of spontaneous ventricular arrhythmias and mortality in patients who received a tiered therapy antitachycardia pacemaker/defibrillator for ventricular tachycardia, fibrillation, or both. Three hundred thirty-seven patients who received a Ventritex CADENCE tiered therapy antitachycardia device at one of 19 participating centers between July 11, 1989 and March 4, 1991 are included in this retrospective analysis. Diagnostic summary data and stored electrograms telemetered from the implanted device were assessed to determine characteristics of recurrent arrhythmias. Mean follow-up was 360 +/- 10 (SEM) days. Thirty-three patients died during follow-up. At least one recurrent ventricular arrhythmia was observed in 205 patients (61%). A total of 7,539 episodes were observed with a mean of 37 +/- 5 per patient. Patients with recurrent ventricular arrhythmias were slightly but significantly older (64 +/- 0.7 vs 59 +/- 1.2 years; P < 0.001) but were not distinguished by gender or underlying structural disease. Patients whose presenting arrhythmia was monomorphic ventricular tachycardia were more likely to experience recurrent ventricular arrhythmias (69% recurrence rate) than patients presenting with ventricular fibrillation or polymorphic ventricular tachycardia (46% recurrence rate; P < 0.001). Cycle length of spontaneous tachycardia was also a predictor of arrhythmia recurrence. Patients having slower ventricular arrhythmias were less likely to remain recurrence free. Mean left ventricular ejection fraction was similar for patients with and without recurrences. Younger age and absence of arrhythmia recurrence but not presenting arrhythmia were predictors of survival. We conclude that age and presentation with monomorphic ventricular tachycardia are important predictors of arrhythmia recurrence for this patient population. Exclusion of patients with monomorphic ventricular tachycardia underestimates the rate of recurrent ventricular arrhythmias and utilization of device therapy. PMID- 7991420 TI - Clinical surveillance of an active fixation, bipolar, polyurethane insulated pacing lead, Part II: The ventricular lead. AB - Since 1989, 72 Telectronics 330-201 active fixation, polyurethane insulated ventricular leads (Accufix) have been implanted at the Mayo Clinic. There were four (5.6%) acute lead related complications (perforation, microdislodgment, and macrodislodgment), three of which led to early reoperation. Over a follow-up time of up to 2.7 years (median 9.4 months), there were six (8.3%) chronic lead related complications but no failures of lead material. Most of these complications developed during the first month, and half of them were transient, with documented improvement later. Two patients (2.8%) required reoperation for chronic complications. At follow-up examination of the pacing thresholds, usually performed about 3 months after implantation, 14.3% of the examined patients had high pacing thresholds necessitating high-output programming. The mechanisms and later evolution of this phenomenon should be further evaluated. PMID- 7991421 TI - The value of rate regularity and multiplicity measures to detect ventricular tachycardia in the presence of atrial fibrillation or flutter. AB - The predominant cause of inappropriate therapy by implantable antitachycardia devices with pacing and nonpacing cardioverter defibrillators, is mistaking a fast ventricular response during atrial fibrillation or flutter with true ventricular tachycardia (VT). The distinction between these arrhythmias is an important consideration in addressing the problem of reducing false-positives in detection mechanisms for implantable devices. Dual chamber analysis that examines atrial and ventricular event ratios has been proposed as a solution to this problem, but would still fail in distinguishing paroxysmal VT requiring treatment from a fast but otherwise benign ventricular response during atrial fibrillation or flutter. In this study, two methods for discriminating these tachyarrhythmias were evaluated. Method 1 examined ventricular rate and rate regularity as a method for VT detection. Method 2 combined rate and regularity as well as an additional multiplicity criterion for recognition of atrial flutter with a fast ventricular response. In 20 patients, Method 1 had 100% sensitivity of VT detection and 80% specificity for detection of atrial fibrillation or flutter. Method 2 had 90% sensitivity and 90% specificity. These results suggest that use of these algorithms in future implantable devices would result in a decrease in false-positive device therapies. PMID- 7991422 TI - Flecainide induced atrial tachycardia with 1:1 ventricular conduction during exercise testing. AB - Wide complex tachycardias may represent a rare proarrhythmic effect of some antiarrhythmic agents. The authors describe a patient who developed a wide complex tachycardia developing during stress testing while on therapy with flecainide, and the difficulty in interpreting the electrocardiogram. This article reviews potential proarrhythmic effects of flecainide in the treatment of atrial dysrhythmias and the difficulty in differentiating associated wide complex tachycardias. PMID- 7991423 TI - The differential diagnosis of a regular tachycardia with a wide QRS complex on the 12-lead ECG: ventricular tachycardia, supraventricular tachycardia with aberrant intraventricular conduction, and supraventricular tachycardia with anterograde conduction over an accessory pathway. PMID- 7991424 TI - Undersensing during ventricular tachyarrhythmias in a third-generation implantable cardioverter defibrillator: diagnosis using stored electrograms and correction with programming. AB - Third-generation implantable cardioverter defibrillators with stored electrograms allow diagnosis of various sensing problems that may lead to an inappropriate device response. Undersensing of ventricular tachyarrhythmias is a potentially serious problem, as it may lead to failure to deliver therapy. To determine the incidence of this problem, we reviewed 98 patients with Ventritex Cadence defibrillator systems and found 2 patients in whom defibrillation therapy was delayed or aborted because of undersensing during induced ventricular tachyarrhythmias. In both cases, examination of stored electrograms revealed variation in electrogram amplitude, which presumably resulted in failure of the autogain feature to increase its sensitivity enough to count each complex. During charging, criteria for redetection of sinus rhythm were met because of this undercounting, leading to failure to deliver defibrillation therapy. This problem was detected in both patients 4-6 weeks following device implant during device testing, and both patients had been started on antiarrhythmic drug therapy prior to this testing. Programming the sinus redetection parameter from nominal to slow, increasing the number of beats necessary to confirm resumption of sinus rhythm, corrected the problem in both patients. Device testing in the electrophysiology laboratory, routinely postoperatively and following initiation of antiarrhythmic drug therapy, and the ability to retrieve stored electrograms are useful in detecting such sensing anomalies. PMID- 7991425 TI - Single lead atrial synchronous ventricular pacing: a dream come true. AB - Single lead, atrial synchronous pacing systems were developed in the late 1970s. Clinical experience has demonstrated the need to position the "floating" atrial electrode in the mid-to-high right atrium and the need for a specially designed pulse generator (with very high atrial sensitivity) to provide a high quality and amplitude atrial electrogram for consistent sensing. A 12-year experience with different electrode configurations, from the first unipolar designed in 1980 to the most recent atrial bipolar electrodes, has confirmed the validity of the original concept and the long-term reliability of the single lead atrial synchronous pacing system, which can reliably produce long-term atrial sensing and ventricular stimulation in the presence of normal sinoatrial function. PMID- 7991426 TI - Multimedia Mania. PMID- 7991427 TI - The "reform" juggernaut: considerations for participants in the health care debate. PMID- 7991428 TI - Transcatheter radiofrequency ablation of ventricular tachycardia following surgical correction of tetralogy of Fallot. AB - Ventricular arrhythmias occur in up to 13.5% of patients after tetralogy of Fallot repair. We describe a patient with a 30-year history of recurrent ventricular tachycardia, which followed the surgical repair of tetralogy of Fallot. Findings at electrophysiological study were consistent with reentry involving an area of slow conduction in the right ventricular outflow tract. Following the transcatheter application of radiofrequency energy in the right ventricular outflow tract, ventricular tachycardia could no longer be induced and has not occurred spontaneously during follow-up (28 months). Thus, transcatheter radiofrequency ablation is an acceptable therapeutic option in some patients with ventricular tachycardia after the surgical repair of tetralogy of Fallot. PMID- 7991429 TI - Cardiac involvement by non-Hodgkin's lymphoma: an unusual presentation of heart conduction disturbances. AB - A 57-year-old man with non-Hodgkin's lymphoma presented with solitary sinus node dysfunction. Superior vena cava syndrome and progressive disturbance of the conduction system requiring dual chamber pacemaker implantation later appeared. Combination chemotherapy and radiation reversed abnormal sinus node function and the AV conduction disturbance, as demonstrated during electrophysiological evaluation. PMID- 7991431 TI - Sinus node modification using radiofrequency current in a patient with persistent inappropriate sinus tachycardia. AB - Radiofrequency catheter modification of the sinus node for persistent inappropriate sinus tachycardia has not been previously reported. This article describes a patient in whom radiofrequency current was used to ablate an incessant automatic tachycardia focus mapped to the region of the sinus node, where a discrete multicomponent electrogram demonstrating earliest atrial activation was recorded. A transient junctional rhythm developed immediately after ablation, with rapid subsequent emergence of a stable rhythm having normal sinus nodal characteristics. PMID- 7991430 TI - Lead dislodgment of a permanent pacemaker due to removal of a temporary pacing electrode. AB - A 63-year-old male received a transvenous temporary pacemaker for bradyarrhythmia following mitral valve replacement and tricuspid valve annuloplasty. A transvenous permanent pacemaker was implanted the following day due to persistence of the bradyarrythmia and pacemaker dependency of the patient. Later the same day during removal of the temporary pacing electrode the permanent pacing lead was dislodged and had to be operatively repositioned. To avoid this complication, the position of pacemaker leads should be checked postoperatively with a frontal and lateral chest radiograph, and fluoroscopy should be used during removal of a temporary lead. PMID- 7991432 TI - Cerebral ultrasonography before and after cardiac surgery in infants. AB - Cerebral ultrasonography was performed in 66 infants before and after open heart surgery in order to study the incidence of cerebral complications. The underlying cardiac malformations were ventricular septal defect (n = 28), transposition of the great arteries (n = 11), tetralogy of Fallot (n = 8), complete atrioventricular septal defect (n = 5), total anomalous pulmonary venous drainage (n = 3), truncus arteriosus communis (n = 2), and complex cardiac malformations (n = 9). In 60 of the 66 infants ultrasonography of the brain preoperatively was normal, 3 had minor structural abnormalities, and 3 had ventriculomegaly of various degrees. Postoperatively, 46 infants had a normal brain ultrasound scan; 6 had slight structural abnormalities; and 5 had slight symmetric or asymmetric widening of the ventricles. Five infants showed severe ventriculomegaly with cerebral atrophy, and in 4 patients there was intracerebral hemorrhage, associated in 2 cases with severe ventriculomegaly. On repeat examinations it was found that up to 4 weeks after the operation an initially normal cerebral ultrasound scan could convert to a pathologic one. Most of those children who showed significant deterioration on the cerebral ultrasound scan suffered from complex cardiac malformations or had severe problems during the postoperative period. PMID- 7991433 TI - Iron supplementation in children after cardiopulmonary bypass for surgical repair of congenital heart disease. AB - A controlled study was carried out to evaluate the effects of postoperative iron therapy on iron status in anemic children after cardiopulmonary bypass. The patients were 8 boys and 9 girls (mean age 6.5 years) who underwent elective closure of atrial septal defect, secundum type. On postoperative day 9, patients were randomly assigned to either iron supplementation with iron sulfate 5 mg/kg until day 56 or to a control group. Hemoglobin, reticulocytes, transferrin saturation, free erythrocyte protoporphyrin, and ferritin were measured, the final outcome measure being postoperative iron status on day 56. The treatment group showed higher transferrin saturations (33.5% versus 18.0%), smaller decreases in ferritin level (+3.0 versus--13.7 ng/ml), and a lower incidence of depleted iron stores (0/8 versus 5/9) than the control group (all data: P < 0.05). Anemic children after cardiopulmonary bypass for surgical repair of congenital heart disease thus benefit from iron supplementation within the first postoperative weeks. PMID- 7991434 TI - Maximal hemodynamic response after the Fontan procedure: Doppler evaluation during the treadmill test. AB - After undergoing the Fontan procedure for congenital heart disease, 16 young patients performed a maximal treadmill test according to the Bruce protocol. The peak velocity of the blood flow in the ascending aorta, stroke index, and cardiac index were measured by continuous-wave Doppler echocardiography at rest and at each stage of the test. The results were compared with those from 18 normal children. The body surface area was similar in the two groups. The endurance time was 37% shorter in the Fontan group than in the control group. From the beginning of exercise until the sixth minute, the increase in stroke index was lower in the Fontan group (NS). After that point, the stroke index was maintained at a high level in the control group but decreased toward its original level in the Fontan group. The response of cardiac index to exercise in the two groups was comparable until the sixth minute, after which the Fontan group failed to maintain an ascending curve. All the hemodynamic values were significantly higher in the control group at maximal exercise; at this point the cardiac index had increased 79% in the Fontan group and 170% in the control group. The subnormal response of the stroke volume at submaximal exercise and the subsequent decrease at maximal exercise following the Fontan procedure are important hemodynamic findings. PMID- 7991435 TI - Descending aortic blood flow velocity as a noninvasive measure of cardiac output in children. AB - In previous work, we postulated that mean aortic flow velocity (MAFV) might be a direct measure of cardiac index. To investigate the assumptions inherent in this relation, we measured body surface area, aortic cross-sectional area (two dimensional ultrasonography) and MAFV (Doppler ultrasonography) in 70 normal children. For a direct check of the relation, we simultaneously measured cardiac index (Fick technique) and MAFV (Doppler ultrasonography) in 25 children after cardiac surgery. In the normal group, we found that body surface area was directly proportional to aortic cross-sectional area (R 0.94), and MAFV at rest was the same in the ascending and descending aorta (t test, p < 0.05). In the intensive care patients, MAFV in the descending aorta was directly proportional to cardiac index over a wide clinical range [MAFV (cm/s) = CI (L/min/m2).7.7 1.2]. The assumptions made when deriving the relation between MAFV and cardiac index appear to be valid whether measured in the ascending or descending aorta. However, the scatter of results limits its clinical value. Mean aortic flow velocity is probably of greater use as a trend indicator and has the potential for continuous display using an esophageal Doppler probe when measured in the descending aorta. PMID- 7991436 TI - Sequential longitudinal evaluation of cardiac growth and ventricular diastolic filling in fetuses of well controlled diabetic mothers. AB - Hypertrophic cardiomyopathy and abnormal ventricular diastolic filling in the infant of the diabetic mother is related to poor maternal glycemic control. Evaluation of fetuses of well controlled diabetic mothers has not been examined. Eleven fetuses of nondiabetic mothers (normals) and 9 fetuses of well controlled insulin-dependent diabetic mothers (FODMs) underwent serial evaluation of cardiac growth and ventricular diastolic filling using M-mode and Doppler echocardiography at 20-26 weeks' (period 1), 27-33 weeks' (period 2), 34-40 weeks' (period 3),m and 48-72 hours after birth (period 4). Indices of right and left ventricular diastolic filling included time velocity integral ratios (E/A and %E/E+A). Cardiac growth and birth weight in the two groups were similar consistent with "good" glycemic control. This conclusion was supported by similar maternal glycosylated hemoglobin (%A1C) prenatally and newborn %A1C and C-peptide values postnatally. Heart rate before and after birth and placental resistance prenatally were similar. Both normals and FODMs demonstrated an increase in left ventricular E/A and %E/E+A ratios from period 1 to 4 (p < 0.0001). This shift occurred earlier (by period 2) in normals (p < 0.01). Right ventricular filling ratios increased by period 4 in normals only (p < 0.01). No differences were noted between the groups during any period. Good glycemic control in FODMs results in normal cardiac growth and ventricular diastolic filling. Progression of diastolic filling is abnormally delayed, however, and is presumably more exaggerated in poorly controlled diabetics. PMID- 7991438 TI - Familial occurrence of discrete subaortic membrane. AB - The first case of multiple family members with discrete subaortic membrane and no other congenital defects is presented. One family member presents with findings suggesting a forme fruste of this disease. Increased surveillance of family members of individuals with discrete subaortic membrane is warranted, as the clinical findings of mild subaortic obstruction may be indistinguishable from those of an innocent flow murmur. PMID- 7991437 TI - New antiarrhythmic drugs in pediatric use: propafenone. AB - Propafenone hydrochloride, a class 1C antiarrhythmic agent, combines sodium channel-blocking effects with beta-blocking capacities and a weak calcium antagonism. The drug exerts marked electrophysiologic effects on accessory atrioventricular pathways. In patients with atrioventricular nodal reentry tachycardia, propafenone is able to block conduction in the fast conducting pathway. In addition, propafenone is very effective in young patients with supraventricular tachycardia based on enhanced abnormal automaticity. In pediatric patients, left ventricular performance remains unimpaired. Proarrhythmic events have been noted in children only occasionally. In accordance with the electrophysiologic profile, intravenous and oral propafenone is an effective agent for treatment of supraventricular tachycardia based on a reentry mechanism and due to abnormal automaticity (i.e., supraventricular tachycardia based on an accessory atrioventricular pathway, atrioventricular nodal reentry tachycardia, junctional ectopic tachycardia, and atrial ectopic tachycardia). In children with ventricular dysrhythmias, efficacy seems to be related to the underlying cardiac diagnosis. Propafenone is well tolerated in the majority of young patients. Incidence of proarrhythmic events seems to be lower with propafenone than with other class 1C agents. However, the risk of these serious adverse events should be taken into account when therapy with propafenone is considered, particularly in patients with structural heart disease. PMID- 7991439 TI - Tricuspid atresia and annular hypoplasia: report of a familial occurrence. AB - Occurrence of a similar cardiac malformation in multiple family members has been reported for many lesions. Neither tricuspid atresia nor tricuspid annular hypoplasia and tricuspid atresia has been described in multiple members of the same family. We report two cases of tricuspid atresia and one case of tricuspid annular hypoplasia with an atrial septal defect in siblings. The findings in this family suggest an autosomal recessive pattern of inheritance for abnormal tricuspid valve morphogenesis. PMID- 7991440 TI - Maternal collagen vascular disease associated with fetal heart block and degenerative changes of the atrioventricular valves. AB - We report the case of a fetus diagnosed at 24 weeks' gestation with complete heart block associated with maternal collagen vascular disease and Sjogren's antibody. Serial fetal echocardiograms noted increased echogenicity along the tricuspid and mitral valves without insufficiency. Postnatally, severe tricuspid insufficiency occurred following placement of an endocardial pacing lead, and severe mitral insufficiency occurred acutely at 2.5 months of age. Both valves were noted at surgery to have fibrotic and calcific chordae tendineae that had ruptured from their papillary muscles. An inflammatory reaction within the fetal heart related to transplacental passage of Sjogren's antibody was likely responsible. PMID- 7991442 TI - Congenital complete atrioventricular block in an infant with Miller-Dieker syndrome. PMID- 7991441 TI - Extraskeletal Ewing's sarcoma of primary cardiac origin. AB - A 13-year-old boy presented with cardiac tamponade. Echocardiography revealed a large mass extending from the right and left ventricles into a large pericardial effusion. Pathology confirmed the first reported case of a primary cardiac extraskeletal Ewing's sarcoma. PMID- 7991443 TI - Pharmacokinetics and organ distribution of the sorbin C-terminal peptides. AB - Sorbin is a 153 amino acid peptide isolated from porcine small intestine. The heptapeptide-amide is the minimal active site of the natural molecule. A comparison of the distribution of C-7 and C-20 sorbin, which have been shown to share the activity of sorbin in increasing intestinal absorption of electrolytes, was undertaken by radioimmunoassay, after perfusion of 200 micrograms/kg/h. A longer half-life in plasma was observed for C-20 sorbin than for C-7 sorbin, with a clearance rate of 18 +/- 4 ml/min/kg vs. 40.6 +/- 13.5 ml/min/kg and a distribution volume of 192 +/- 35 ml/kg vs. 286 +/- 123 ml/kg. The accumulation of tritiated C-7 sorbin was observed in enterocytes, serosal acini of the salivary glands, and fundus chief cells. The recovery of intact peptide in the intestine was 0.06% per gram of tissue. Eighteen percent of the peptide was detected in urine. PMID- 7991444 TI - Peptide histidine isoleucine-induced elevations in ACTH and corticosterone in the rat. AB - Peptide histidine isoleucine (PHI) is one of many neuropeptides found in both the periphery and the central nervous system (CNS). In the present work, we compared the effects of intravenous (IV) and hypothalamic (PVN) administration of PHI on plasma ACTH and corticosterone (CORT) secretion 2 h after the onset of light in fasted, freely moving male rats. The PVN administration of PHI (0.15, 0.30, 1.50, and 3.0 nmol/rat) elicited significant, dose-dependent increases in plasma ACTH and CORT concentrations that were maximal at 15 min postadministration and fell gradually over 60-120 min. The highest dose of PHI increased ACTH and CORT to 821% and 340% of time-matched control levels, respectively. The IV injection of PHI (3.0 nmol/rat) also raised plasma ACTH and CORT levels in these animals. However, the peak response (at 15 min postinjection) to the same dose of PHI was much lower following IV administration (ACTH 188% of control; CORT 210% of control) than after PVN administration. These results suggest that endogenous PHI may be a physiological regulator of ACTH and CORT secretion in rats and that the PVN is a major site for its action. PMID- 7991445 TI - Distribution of gastrin-releasing peptide/bombesin-like immunoreactivity in the rainbow trout brain. AB - The distribution of gastrin-releasing peptide (14-27)/bombesin-like immunoreactivity was studied in the brain of the teleost Oncorhynchus mykiss using an indirect immunoperoxidase technique. Cell bodies were only found in the hypothalamic nuclei posterioris periventricularis, the anterior part of the recessus lateralis, and in the recessus posterioris. Immunoreactive fibers were widely distributed in the diencephalon, midbrain, and hindbrain. The highest density of immunoreactive fibers was found in the hypothalamus, whereas a moderate to low density of fibers was visualized in the periventricular thalamus. In the midbrain, a moderate density of fibers was observed at the level of the nuclei lateralis and centralis of the torus semicircularis, the stratum album centrale of the optic tectum, the nucleus of the rostral mesencephalic tegmentum, the nuclei lateralis valvulae, the lemnisci lateralis, istmi and locus coeruleus, as well as in the hindbrain at the level of the nuclei gustatorius secundarius, cerebelli, descendens nervi trigemini, and funiculi lateralis. These data suggest that the peptide could be involved in neuroendocrine (LT, nRL, nRP), visual (OT, nRTM, TS, Is), auditory (TS), and nociceptive (Vd, nufl) mechanisms. PMID- 7991446 TI - Inhibitory effect of somatostatin-14 and some analogues on human natural killer cell activity. AB - The effect of somatostatin-14 (SST) and the SST analogues SMS and RC160 on human natural killer (NK) activity mediated by large granular lymphocytes (LGL), as well as on IL-2- and/or anti-CD16 monoclonal antibody (mAb)-induced activation of these cells, was investigated. The NK activity of LGL was studied by the release of 51Cr by the erythroleukemia-derived cell line K562, whereas 51Cr release by the P815 murine mastocytoma-derived cell line, for which lysis was redirected by the use of an anti-CD16 mAb, was used to study the cytolytic potential of these cells. IL-2 was used at the final concentration of 100 IU and was incubated overnight with LGL. SST and the analogues, added to these systems at final doses ranging from 10(-12) to 10(-5) M, were inhibitory of the NK cell activity to K562, with a dose-response curve starting from 10(-8) M and reaching a significant level at 10(-6) M. On the contrary, no effect was observed on the redirected killing assay to P815 and on the IL-2-induced activation of NK cells. These results provide additional evidence for the immunomodulatory action of somatostatin. PMID- 7991447 TI - Dithiothreitol, sodium chloride, and ethylenediaminetetraacetic acid increase the binding affinity of [125I]angiotensin IV to AT4 receptors in bovine adrenal cortex. AB - The present studies demonstrate that the sulfhydryl reducing agent, dithiothreitol (DTT), increases the specific binding of [125I]angiotensin IV ([125I]AIV) to AT4 receptors in bovine adrenal cortical membranes. Both the degree of stimulation and the pharmacological selectivity of [125I]AIV binding in the presence of DTT were quantitatively different depending on the contents of the assay buffer. Similar effects were also observed using a different sulfhydryl reducing agent, 2-mercaptoethanol (2-MCE). These sulfhydryl reducing agents (100 mM) produced a 200% increase in specific [125I]AIV binding in an assay buffer that has been used to characterize the novel AT4 receptor subtype. A much larger stimulation (700%) of specific [125I]AIV binding was found when the assay was conducted in a buffer that has been used to characterize ligand binding to the AT1 receptor. Ligand association studies indicated that 0.3 nM [125I]AIV displayed similar equilibrium kinetics and stability in both the AT4 and AT1 buffers. Ligand saturation studies indicated that [125I]AIV bound with high affinity (Kd = 6 nM) in the AT4 buffer system, but bound with lower affinity (Kd = 32 nM) in the AT1 buffer system. Removal of NaCl and EDTA from the AT4 buffer also resulted in low-affinity [125I]AIV binding (Kd = 33 nM). The subsequent inclusion of NaCl, EDTA, or DTT resulted in higher-affinity [125I]AIV binding (KdS = 3-14 nM). No significant effects on the apparent density (Bmax) of AT4 receptors were observed.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7991448 TI - Brain atriopeptin mediates AV3V depressor response. AB - In urethane-anesthetized rats, sodium L-glutamate (Glu) microinjection into the anteroventral third ventricle region (AV3V) induced a depressor response, but the heart rate remained unchanged, whereas Glu injection into its surrounding areas or normal saline injection into the AV3V had no effect on the arterial pressure and heart rate. Bilateral preinjection of procaine or atriopeptin III antiserum into the nucleus paraventricularis (NPV) and methyl atropine (IV) markedly attenuated the AV3V depressor response, but the hypotensive response was not significantly affected by phentolamine or propranolol (IV), indicating that atriopeptin in the NPV mediates the AV3V depressor response, and excitation of the cardiac vagus is also involved in this response. PMID- 7991449 TI - Distribution of FMRFamide-like immunoreactivity in the brain of the lizard Podarcis sicula. AB - The distribution of FMRFamide-like immunoreactive peptides was investigated in the brain of the lizard, Podarcis sicula, using the indirect immunofluorescence technique. The main populations of FMRFamide-immunoreactive cell bodies were located in the forebrain. In the telencephalon, FMRFamide-containing neurons were found both in the pallium and subpallium, namely in the medial cortex, the anterior olfactory nucleus, the nucleus accumbens, the septal nuclei, the nucleus of the medial forebrain bundle, and the nucleus of the diagonal band of Broca. In the diencephalon, a dense accumulation of FMRFamide-immunoreactive neurons was observed in the area preoptica lateralis, the nucleus suprachiasmaticus, the nucleus periventricularis hypothalami, the area lateralis hypothalami, and the dorsal region of the nucleus geniculatus lateralis. In the midbrain, sparse immunoreactive perikarya were found in the tegmentum of the mesencephalon. FMRFamide-immunoreactive fibers were visualized in all regions containing positive cell bodies. In particular, dense bundles of immunoreactive processes were seen in the area preoptica lateralis, in the hypothalamus, and in the median eminence. The tectum and the basal mesencephalon were also densely innervated. Conversely, the caudal brain stem only exhibited scarce immunoreactive processes. The distribution pattern of FMRFamide-immunoreactive neurons in the brain of Podarcis sicula exhibits a number of similarities with that reported in mammals, but significantly differs from that reported in amphibians and fish, suggesting that the neuromodulatory functions of FMRFamide may have diverged during the emergence of terrestrial life. PMID- 7991450 TI - Migrating motor complex recorded spontaneously and induced by motilin and erythromycin in an ex vivo rabbit intestinal preparation. AB - We investigated basal motility and the motor effects of motilin, erythromycin, and prostigmine on segments of rabbit gastrointestinal tract removed from extrinsic neural and vascular pathway and immersed in an oxygenated organ bath. Motility was recorded by means of four strain gauges sutured on the serosal surface of the segment. During basal recording, clusters of duodenal contractions that propagated distally, resembling phase III activity of migrating motor complex, were seen. Motilin (10(-6) M) and erythromycin (10(-6) M) induced a propagated cluster of contractions similar to the phase III recorded during the basal period. Prostigmine (10(-6) M) induced a simultaneous increase in gastric and small intestinal motility. Atropine (10(-5) M) prevented the motor effect of motilin, erythromycin, and prostigmine. Thus, MMCs do not appear to require central input for initiation and propagation. Motilin and erythromycin stimulate MMCs through an enteric cholinergic mechanism; therefore, the previously reported smooth muscle receptors for both substances were not apparent in the ex vivo preparation. PMID- 7991451 TI - Estrogen increases affinity of oxytocin receptors in the medial preoptic area anterior hypothalamus. AB - Analysis of binding data from saturation experiments using a radiolabeled oxytocin antagonist ([125I]OTA) demonstrated an increase in binding affinity after treatment with 5 micrograms estradiol benzoate (EB) for 3 days in membrane fractions from the medial preoptic area-anterior hypothalamus (MPOA-AH) of ovariectomized (OVX) rats. Analysis of data from competition experiments revealed high- and low-affinity [125I]OTA binding sites in the MPOA-AH, the medial basal hypothalamus (MBH), and hippocampus of OVX controls. Three days of EB treatment reduced low-affinity binding sites in the MPOA-AH and MBH, but not in the hippocampus. Treatment of membrane fractions from the MPOA-AH of oil-treated OVX rats in vitro with 100 nM OT or with estrogen or progesterone conjugated to bovine serum albumin (E-BSA and P-BSA) also reduced low-affinity [125I]OTA binding sites but BSA alone did not. PMID- 7991452 TI - Developmental changes of enzymes involved in peptide degradation in isolated rat brain microvessels. AB - The specific activities of aminopeptidase A (APA), aminopeptidase M (APM), and dipeptidyl-aminopeptidase IV (DP IV) were determined in isolated brain microvessels and in brain homogenate of rats with different ages (between 1 and 8 weeks old). In addition, the blood-brain barrier (BBB)-specific enzymes gamma glutamyltranspeptidase (gamma-GT) and alkaline phosphatase (ALP) were measured. As similarly described by others, gamma-GT activity increased during this time period by fourfold, whereas ALP increased between weeks 1 and 2 and declined thereafter. DP IV activity increased fivefold during the first 8 weeks after birth and APM activity increased by twofold. A decrease of APA activity was found between weeks 1 and 2 after birth followed by an increase thereafter. The development of aminopeptidase activities responsible for the processing of specific neuropeptides acting on brain microvessels may be important in the development of regulation processes for cerebral blood flow and BBB permeability in the maturing animal. PMID- 7991453 TI - Isolation, sequence, and bioactivity of FMRFamide-related peptides from the locust ventral nerve cord. AB - The ventral nerve cord of the locust, Locusta migratoria, was examined for the presence of FMRFamide-related peptides (FaRPs). RP-HPLC coupled to an RIA specific for extended -RFamides revealed the presence of several FaRPs eluting at different percentages of acetonitrile. The sequences of five of these peptides were determined. Two sequences are identical to the two peptides previously sequenced from brain and retrocerebral complex of Locusta. These two peptides (PDVDHVFLRFamide and ADVGHVFLRFamide) were inhibitory when tested on locust oviduct contractions. The other peptides are novel with sequences of GQERNFLRFamide, AXXRNFIRFamide, and AFIRFamide. The synthesized peptides were stimulatory when tested on locust oviduct contractions, increasing the frequency and amplitude of spontaneous contractions and resulting in a basal contraction. PMID- 7991454 TI - Demonstration of [D-Ala2]deltorphin I-like immunoreactivity in mucosal epithelial cells of the rat gastrointestinal tract. AB - Using a specific antiserum to [D-Ala2]deltorphin I (DADTI), a delta-opioid receptor ligand, the localization of positive structures was studied in rat gastrointestinal tract by immunocytochemistry. Immunoreactive staining was not detected in the stomach, colon, or neuronal elements of any gastrointestinal tissue. However, positive cells were distributed in the mucosal epithelium of the small intestine, including the duodenum, jejunum, and ileum. The density of positive cells was highest at a proximal part of the jejunum and was gradually decreased toward the duodenum or the distal end of the intestine. These positive cells had spindle-like somata that tended to locate more closely to the lumen compared with nonimmunoreactive cells. Some of the positive cells extended cytoplasmic basal processes toward the lamina propria. Immunoelectron microscopy revealed that positive reaction products occurred within the secretory granules as well as in the cytoplasm. Because these positive granules were frequently observed in the apical cytoplasm beneath the microvilli, it is suggested that the DADTI-like molecule(s) may be secreted to the lumen. PMID- 7991455 TI - Pharmacokinetics of DGAVP in plasma following intranasal and oral administration to healthy subjects. AB - A pharmacokinetic study was carried out to assess the bioavailability of desglycinamide-[Arg8]vasopressin (DGAVP, Org 5667). DGAVP (2 mg) was administered both intranasally and orally to healthy subjects with a treatment interval of 1 week. Blood samples were taken regularly between 15 min before and 210 min after administration and were assayed for DGAVP by radioimmunoassay. In all subjects endogenous vasopressin (AVP) levels were detectable. Peak levels of DGAVP occurred at 15 min after both treatments. The mean absorption half-life was 8.7 and 7.3 min and the mean elimination half-life was 38 and 34.6 min for the intranasal and oral route of administration, respectively. The bioavailability of orally administered DGAVP was low compared with the intranasally administered drug; the relative bioavailability of oral/nasal administration was 0.7%. The results indicate that DGAVP is absorbed rapidly after both oral and intranasal administration, but the intranasal route of administration of DGAVP is 100 times more effective in increasing plasma DGAVP levels. PMID- 7991456 TI - CNS effects of peptides: a cross-listing of peptides and their central actions published in the journal Peptides, 1986-1993. AB - The centrally mediated effects of peptides as published in the journal Peptides from 1986 to 1993 are tabulated in two ways. In one table, the peptides are listed alphabetically. In another table, the effects are arranged alphabetically. Most of the effects observed after administration of peptides are grouped, wherever possible, into categories such as cardiovascular and gastrointestinal. The species used in most cases has been rats; where other animals were used, the species is noted. The route of administration of peptides and source of information also are included in the tables, with a complete listing provided at the end. Many peptides have been shown to exert a large number of centrally mediated effects. PMID- 7991457 TI - Isolation of a novel peptide with a unique binding profile from human brain cortex: Tyr-K-MIF-1 (Tyr-Pro-Lys-Gly-NH2). AB - Tyr-MIF-1 (Tyr-Pro-Leu-Gly-NH2), Tyr-W-MIF-1 (Tyr-Pro-Trp-Gly-NH2), and MIF-1 (Pro-Leu-Gly-NH2) are biologically active peptides previously isolated from brain tissue. We now have used size exclusion chromatography and several consecutive rp HPLC steps monitored by RIA to isolate a structurally related peptide from human brain cortex with the sequence Tyr-Pro-Lys-Gly-NH2 (Tyr-K-MIF-1). Determination of the sequence, electrospray mass spectrometry, and comparison of its chromatographic behavior with synthetic Tyr-K-MIF-1 confirmed the structure. Unlike Tyr-MIF-1 and Tyr-W-MIF-1, Tyr-K-MIF-1 does not bind to the mu opiate site; unlike MIF-1, Tyr-K-MIF-1 can bind to the Tyr-MIF-1 site. Of these peptides, only Tyr-K-MIF-1 binds to its own site in brain tissue prepared in Tris buffer. Thus, a new member of the Tyr-MIF-1 family of peptides, with a unique profile of binding, has been isolated from human brain cortex. PMID- 7991458 TI - Design of a potent peptide inhibitor of the epidermal growth factor receptor tyrosine kinase utilizing sequences based on the natural phosphorylation sites of phospholipase C-gamma 1. AB - Peptides that possess primary sequences identical to segments surrounding the natural phosphorylation sites of phospholipase C-gamma 1 (i.e., tyrosines 472, 771, 783, and 1284) have been synthesized and evaluated with respect to substrate kinetics for the epidermal growth factor receptor tyrosine kinase. A peptide that was based on tyrosine 472 was the superior substrate in terms of lowest Km value at 37 microM and had the following amino acid sequence: Lys-His-Lys-Lys-Leu-Ala Glu-Gly-Ser-Ala-Tyr472-Glu-Glu-Val. This peptide sequence was used as a foundation to make amino acid substitutions and/or chemical modifications directed toward the synthesis of a potent peptide inhibitor. As a result, a nine amino acid peptide was synthesized having a K(i) of 10 microM. PMID- 7991459 TI - Structure, localization, and action of buccalin B: a bioactive peptide from Aplysia. AB - The cholinergic motor neurons for the accessory radula closer (ARC) contain several neuropeptides that affect muscle contractions. In the present study, we have purified and sequenced a sixth ARC neuropeptide, using a combination of high pressure liquid chromatography and bioassays. This neuropeptide, Gly-Leu-Asp-Arg Tyr-Gly-Phe-Val-Gly-Gly-Leu-amide, has been named buccalin B (BUCb) because it is significantly homologous to the previously characterized neuropeptide buccalin A. BUCb was found to be two-three times more potent than buccalin A in depressing motor neuron induced contractions. PMID- 7991460 TI - Isolation and characterization of a diuretic peptide common to the house fly and stable fly. AB - An identical CRF-related diuretic peptide (Musca-DP) was isolated and characterized from whole-body extracts of the house fly, Musca domestica, and stable fly, Stomoxys calcitrans. The peptide stimulates cyclic AMP production in Manduca sexta Malpighian tubules and increases the rate of fluid secretion by isolated Musca domestica tubules. The 44-residue peptide, with a mol.wt. of 5180, is amidated, and has the primary structure: NKPSLSIVNPLDVLRQRLLLEIARRQMKENTRQVELNRAILKNV-NH2. Musca-DP has a high percentage of sequence identity with other characterized CRF-related insect diuretic peptides. PMID- 7991461 TI - Localization of motilin-immunopositive cells in the rat intestine by light microscopic immunocytochemistry. AB - Motilin-immunopositive cells (Mo cells) are known to exist in the upper small intestine of many species including man. However, the possible presence of Mo cells in the rat gastrointestine has remained obscure because antiserum against it raised in rabbit was found not to cross-react with motilin in the rat gastrointestine. The present study was designed to investigate the distribution of Mo cells in the rat gastrointestine by the peroxidase-conjugated second antibody method using newly raised chicken anti-motilin serum (CPV3). This antiserum was suggested to recognize the N-terminal region of the motilin molecule by enzyme-linked immunosorbent assays and immunocytochemical absorption test. Mo cells detected in the rat gastrointestine by immunocytochemistry were found to be distributed in the duodenum (1.5 cells/mm2), jejunum (2.2 cells/mm2), and ileum (0.028 cells/mm2), and no positive cells were found in the gastric body, gastric antrum, cecum, colon, or pancreas. The immunopositive cells in the rat intestine were spindle shaped or polygonal, scattered throughout the epithelium of the villi and crypts, and similar to those commonly observed in the upper small intestine of other species. These results indicate for the first time that motilin-immunopositive cells do exist in the rat intestine. PMID- 7991462 TI - Immunoelectron microscopy of different forms of glomerulonephritis in routine biopsy material. AB - Renal biopsies were investigated of patients with IgA or membraneous glomerulonephritis or with systemic lupus erythematosus by light microscopy, electron microscopy, light microscopic immunohistology and by immunoelectron microscopy using the post-embedding technique applied to LR-White embedded tissue. Aim of the study was to explore whether immunoelectron microscopy is reproduced on routine biopsy material and in accordance with light microscopic immunohistological findings. The study shows that immunoelectron microscopy can be applied to routine biopsy material and gives reproducible results. The applied method proved to be reliable, and, hence, routine biopsy material may be used for further studies concerning subcellular mechanisms in immunocomplex deposition and removal. PMID- 7991463 TI - AgNOR content and PCNA expression in transplanted malignant neurinoma in rats. AB - Malignant neurinomas can be induced in BD IX rats by transplacental application of ethylnitroso-urea during pregnancy. Tumors develop in the offspring in trigeminal and spinal nerves and can be easily transplanted upon rats of the same strain. During the first passages a considerable shortening of subsequent induction periods takes place. Concurrently, silver stained Nucleolar Organizer Regions (AgNORs) increase in number and other measured AgNOR parameters change in a similar way. The number of cells that express the proliferation marker PCNA equally becomes more frequent during the first subcutaneously transplanted generations. There is high correlation between AgNOR parameters, number of PCNA expressing cells, induction times and passage. It is concluded that the first generations of the transplantation model of these tumors can be used to test the validity of proliferation indicators. Our results show further that AgNORs in fact belong to the group of markers of proliferation. PMID- 7991464 TI - The value of the AgNOR staining method in identifying carcinoma in situ testis. AB - An early and reliable diagnosis is necessary in order to have the chance of a curative therapy of Carcinoma in situ testis (Cis). Forty-six testicular biopsies were investigated to assess the value of the AgNOR staining method in comparison to placental alkaline phosphatase (PLAP) immunostaining. Both methods provided corresponding results and identical tumor cells were recognized in serial sections. The mean AgNOR counts per nucleus were 26.86 (19-52, SD: 2.68) for CIS cells, 8.18 (5-14, SD: 2.20) for spermatogonia and 12.96 (9-18, SD: 2.44) for Sertoli cells, without the counts overlapping within these three groups. Even single CIS cells are easily and reliably recognizable by their typical AgNOR pattern and their high AgNOR count per nucleus. The independent estimation of 9 testicular biopsies with the AgNOR staining method and the PLAP immunostaining correspondingly revealed 7 biopsies with CIS. Two biopsies lacked tumor cells. The AgNOR staining method can be recommended as an additional diagnostic tool in identifying CIS, because of the short and convenient staining procedure, low costs and the applicability on formalin-fixed and paraffin-embedded material. PMID- 7991466 TI - Morphometrical analysis of cystadenolymphoma (Warthin's tumor). Subclassification and characterization of the lymphoid stroma in comparison with gastric lymphoid follicles. AB - Morphometrical analysis was applied to cystadenolymphoma (Warthin's tumor, adenolymphoma: CAL). By quantitative analysis of tissue sections, the examined cases were divided into three subtypes according to the ratio of the lymphoid stroma (LS) to the whole tissue: type I "stroma-rich type", the LS of this type was more than 57% of the whole tissue; type II "typical type", the LS of this type was 37% to 56% of the whole tissue; and type III "stroma-poor type", the LS of this type was less than 36% of the whole tissue. The average age of the patients in subtypes I, II and III was 57.7, 68.0, and 62.4 years, respectively. The age of the patients with type I CAL was significantly lower than that of those with type II CAL. In many type II cases, a reticular distribution of IgE in the germinal centers was frequently observed. From an analysis of the sections immunohistochemically stained with monoclonal antibodies to B and T cells, there appeared to be a trend that the greater the percentage of the LS to the whole tissue, the lower the ratio of B cell region to the LS. In contrast to CAL, an analysis of the change of the ratio of B cell region to the lymphoid follicles (LF) seen in the gastric mucosa of patients with chronic gastritis showed that the larger the volume of LF, the higher the ratio of the B cell region to the entire LF.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7991465 TI - Clonality of benign lymphoid hyperplasia in orbit and conjunctiva. AB - In order to thoroughly characterize the clonal population of lymphoid hyperplasia of the orbit and conjunctiva, we investigated six cases which were histologically proven to be benign lymphoid hyperplasia. We analyzed the clonal rearrangements of the antigen receptors and bcl-2 gene, Epstein-Barr virus (EBV), and human T cell leukemia virus type 1 (HTLV-I) by Southern blot and/or polymerase chain reaction (PCR), and performed in situ hybridization for mRNA of kappa and lambda immunoglobulin. Five cases showed rearrangements of immunoglobulin heavy chain gene (JH) and/or light chain gene (J kappa), and the monoclonal V-J recombination of JH in PCR. However, the rearranged bands were much more faint than was the germ-line band. We considered the monoclonal population of B cells small. Two of the five cases recurred locally after four and nine years respectively. Because benign lymphoid hyperplasias frequently contain an occult monoclonal B-cell population, a follow-up should be conducted. The remaining case in our investigation showed a rearrangement of the T-cell-receptor gene and proviral DNA of HTLV-I, and it showed rapid progress to adult T-cell leukemia after the biopsy. EBV and bcl-2 gene rearrangements were not observed in any of the six cases we studied. PMID- 7991467 TI - Phyllodes tumor of the breast. An immunohistochemical study of 28 cases with special attention to the role of myofibroblasts. AB - The presence of myofibroblasts in the stroma of Phyllodes tumor of the breast has been documented in single cases by means of electron microscopy and immunohistochemistry. In this study, we re-evaluate the immunophenotype exhibited by 28 Phyllodes tumors (14 benign, 6 borderline and 8 malignant) in order to state the relevance of myofibroblasts as active stromal elements in these tumors. Vimentin showed positive immunostaining in the stroma of all the cases (100%), muscle-specific actin in 21 (75%), and desmin in 7 (25%). By contrast, stromal cells were uniformly negative for S-100 protein, keratins (AE1/AE3 and CAM 5.2), and epithelial membrane antigen (EMA). The epithelial component showed the typical two-layered arrangement of ducts in every case. Myoepithelial (outer) cells immunostained with muscle-specific actin and S-100 protein, and in some cases with EMA and keratins, whereas the epithelial (inner) layer did so with keratins and EMA. To conclude, we have found a prominent myofibroblastic differentiation in stromal cells of many of such tumors. Our results also prove that no differences in intensity or distribution of such actin-positive stromal cells are seen between benign, borderline or malignant counterparts. PMID- 7991468 TI - The contraction state of myofibrils during global ischemia and after reperfusion following different forms of cardiac arrest. Correlation with metabolic parameters in the canine heart. AB - This study was undertaken in order to obtain information on the mode of reaction of the contractile apparatus after different forms of cardiac arrest, global ischemia and reperfusion, as well as on possible correlations between the contraction state of myofibrils and biochemical parameters. During the survival time, before the level of 3 mumol/gww creatine phosphate (CP) is reached, the contraction state shows only minor changes. During the revival time in which ATP tissue concentrations decay to 4 mumol/gww, the contribution of ATP, lactate, anorganic phosphate (Pa) and acidosis to the degree of relaxation depends on the method of cardiac arrest. At defined biochemical values, the degree of relaxation is comparable after aortic cross clamping (ACC) and St. Thomas perfusion, but significantly different compared to HTK perfusion. Thus, during the revival time, the relaxation of sarcomeres depends predominantly on the composition of the solutions used for cardiac arrest. The re-entry of contraction below 3 mumol/gww ATP is correlated with the ATP concentration, independent of the form of cardiac arrest. Reperfusion after HTK or St. Thomas cardioplegia and reversible ischemia leads to the focal formation of contraction bands, which do not occur during ischemia. This contraction state is significantly more pronounced after reperfusion of St. Thomas arrested hearts. Thus, the contraction state of myofibrils is influenced not only by alterations in metabolite concentrations, but also by the composition of cardioplegic solutions and by the characteristic conditions (sufficient energy, oxygen and Calcium) during reperfusion. PMID- 7991469 TI - Glomerular expression of type III and type IV collagens in benign nephrosclerosis: immunohistochemical and in situ hybridization study. AB - The development of glomerular sclerosis in benign nephrosclerosis (BNS) was studied. We investigated the intraglomerular expression of type III and IV collagens and their mRNAs by immunohistochemistry and by the in situ hybridization method. Formalin-fixed paraffin sections from 28 patients with BNS and 10 control cases were stained by the avidin-biotin complex (ABC) method using monoclonal antibodies for human type III and IV collagens. In the course of the sclerotic process of the glomerulus in BNS, the glomerular staining intensity of type IV collagen increased. The strongest staining was observed in the glomerulus at the early sclerotic stage, and intensity decreased slightly at the later stages. Although type III collagen was absent in normal and nonsclerotic glomeruli, peripheral regions of the sclerotic glomeruli were positive at the early sclerotic stage. Later, type III collagen was diffusely observed in the completely hyalinized glomeruli. The expression of type III and type IV collagen mRNAs was detected in the glomeruli of BNS by the non-radioactive in situ hybridization method using thymine-thymine (T-T) dimerized synthetic oligonucleotides. The number of mRNA positive cells for type III and type IV collagens increased at the presclerotic and early sclerotic stages. But these cells gradually decreased in number as glomerular sclerosis developed. We concluded that type III collagen was presumably synthesized by the intraglomerular cells and may contribute to the development of glomerular sclerosis in BNS along with type IV collagen. PMID- 7991470 TI - Disseminated peritoneal leiomyomatosis. An unusual case. AB - Disseminated peritoneal leiomyomatosis (DPL) is a very rare disorder, characterized by the presence of multiple intraabdominal smooth muscle nodules and frequently associated with a high estrogen production. We report on a 43-year old woman with DPL and simultaneous bilateral ovarian cystic teratomas. There were no overt endocrine abnormalities. Due to distinct cellular pleomorphism on a frozen section, complete removal of smooth muscle nodules was suggested, but could not be achieved because of severe bleeding. Two years after resection of the ovarian tumors but with residual DPL, the patient is doing well, with no evidence of malignant disease. PMID- 7991471 TI - Anaplastic thyroid carcinoma with osteosarcomatous differentiation. AB - A case of a thyroid tumour with the cytological and histological pattern of anaplastic carcinoma with extensive osteosarcomatous differentiation in a 54-year old Kaukasian woman is presented. Immunohistochemical examination revealed keratin-vimentin co-expression in anaplastic tumour areas. According to the WHO classification of thyroid tumours the present tumour has to be classified as an anaplastic carcinoma. A retrospective survey revealed only twenty-four comparable cases in the literature. The present tumour most likely represents an example of a neoplastic epithelial-mesenchymal metaplasia. The possible mechanisms of the occurrence of thyroid tumours with mixed epithelial-mesenchymal differentiation are briefly discussed. PMID- 7991472 TI - Sickle cell disease. Still a management challenge. AB - Early diagnosis of sickle cell disease enables physicians to initiate prompt treatment and provide appropriate education and counseling for patients and their families. In this article, Dr Burdick reviews the management of major complications of the disorder, discusses the psychosocial impact, and examines the possibilities for cure in the future. PMID- 7991473 TI - Obsessive-compulsive disorder. How to free patients from intrusive thoughts and rituals. AB - The antidepressants clomipramine hydrochloride (Anafranil), fluoxetine hydrochloride (Prozac), and sertraline hydrochloride (Zoloft) are the main choices for pharmacologic treatment of obsessive-compulsive disorder. Often, drug doses for obsessive-compulsive disorder are higher than for depression, and improvement occurs more slowly and is often only partial. Behavior therapy involving exposure to feared objects or situations and prevention of ritualistic behavior complements pharmacologic treatment. Referral to a behavioral therapist may be necessary to achieve recovery. PMID- 7991474 TI - Practical advice on rattlesnake bites. PMID- 7991475 TI - Real issue of tort reform. PMID- 7991476 TI - Thrombolysis after acute myocardial infarction. Who should be added to inclusion criteria? AB - Thrombolytic therapy has been proven to be highly effective and safe in patients presenting with acute myocardial infarction. Its use may reduce mortality rates by as much as 50%. Accelerated administration of tissue plasminogen activator (Activase) combined with intravenous heparin shows particular success in reducing mortality rates, especially in patients with anterior infarcts. However, strict compliance to the classic inclusion criteria has limited the number of patients, excluding several groups who have been shown to benefit from thrombolysis: The elderly appear to benefit from early thrombolysis even more than do their younger counterparts. Patients with inferior myocardial infarction and bundle-branch blocks also benefit. Recent trials suggest that thrombolytic therapy can be cautiously extended to patients presenting late (up to 24 hours) after onset of symptoms. Certain patients with a history of cerebrovascular disease or recent surgery, patients with severe hypertension, and those having undergone cardiopulmonary resuscitation should not necessarily be excluded from consideration. PMID- 7991477 TI - Adjuvants to thrombolysis after acute myocardial infarction. Does adding antiplatelet agents, antithrombotics, or angioplasty make a difference? AB - Thrombolytic therapy markedly reduces mortality and improves left ventricular function in patients with acute myocardial infarction. Improvement may be even more substantial with adjuvant therapy. Aspirin has proved to be effective adjuvant therapy to thrombolysis. Other antiplatelet agents that may be even more effective or have an additive effect with aspirin are being studied. The role of antithrombotic agents, especially heparin, as adjuvant therapy remains unclear. Immediate cardiac catheterization with angioplasty has been used as adjunct therapy, but its routine use is not recommended. Instead, elective angioplasty (cardiac catheterization, with revascularization as indicated) should be undertaken in patients with recurrent ischemia. Angioplasty as an alternative to thrombolysis may be advantageous in certain patients, such as those presenting in cardiogenic shock or with contraindications to thrombolysis. The role of primary angioplasty in other groups (eg, the elderly, those with anterior myocardial infarction) remains unclear, and further trials are necessary before it can be recommended over thrombolytic therapy. Equipment needed for angioplasty limits its practicality, whereas thrombolytic therapy can be administered at most US hospitals. PMID- 7991478 TI - Alcoholic hepatitis. Recent advances in pathogenesis and therapy. AB - Although the pathogenesis of alcoholic hepatitis is not fully understood, significant progress has been achieved in recent years. The role of the immune system in initiating and perpetuating the injury is being defined. Abstinence from alcohol is probably the most effective treatment. Nutritional support has not had a consistently beneficial effect on survival rates. There is renewed interest in the use of corticosteroids in patients with severe disease. Orthotopic liver transplantation is appropriate for some patients with end-stage liver disease. PMID- 7991479 TI - Acute exacerbations of chronic bronchitis. Preventing treatment failures and early reinfection. AB - Although antimicrobial agents from a number of classes have been used with a good degree of clinical success for acute bacterial exacerbations of chronic bronchitis, the incidence of resistance by beta-lactamase-producing strains to certain penicillins and cephalosporins continues to increase and represents a growing clinical problem. There also have been reports of significant resistance by Streptococcus pneumoniae to tetracyclines and of treatment failures caused by this organism among patients receiving fluoroquinolones. The emergence of penicillin-resistant pneumococci in North America also is of concern. Although first-generation cephalosporins are no longer regarded as first-line therapy or optimal alternatives for acute exacerbations of chronic bronchitis, more recently developed agents of this class have better activity against the primary pathogens, and their efficacy and safety have been demonstrated in a number of clinical trials. Newer macrolide agents probably should be reserved for infections caused by atypical organisms. PMID- 7991481 TI - An overdose patient who refuses help. PMID- 7991480 TI - Skin signs of systemic disease. When the problem is more than skin-deep. AB - The cutaneous manifestations of systemic diseases are diverse. In some cases, they are the first signs of an underlying disorder, such as Cowden's disease, dermatomyositis, and Lyme disease. Sister Mary Joseph's nodule (metastatic involvement of the umbilicus) is an ominous sign of internal malignant disease. Drug-induced skin necrosis may result from therapy with coumarin (Coumadin, Panwarfin, Sofarin) or heparin. PMID- 7991483 TI - The MRCGP: a passport to a practice. PMID- 7991482 TI - The driver, the doctor and the law. PMID- 7991484 TI - Why lifelong diet matters in coeliac disease. PMID- 7991485 TI - Innovations in gastrointestinal diseases. PMID- 7991486 TI - Current thinking on screening for large bowel cancer. PMID- 7991487 TI - Problem drug users: a problem for the GP? PMID- 7991488 TI - A survivor of teenage sexual abuse. PMID- 7991489 TI - Managing the driver who drinks. PMID- 7991490 TI - Make the best use of your time. PMID- 7991491 TI - The GP, the community and shared psychiatric care. PMID- 7991492 TI - Headaches in children: action or reassurance. PMID- 7991493 TI - Child accidents: common, serious and preventable. PMID- 7991494 TI - 'My child won't eat!'. PMID- 7991495 TI - Facing the measles epidemic. PMID- 7991496 TI - Knowing when to suspect child sexual abuse. PMID- 7991497 TI - Reasons for investigating the jaundiced child. PMID- 7991499 TI - 1994 American Association of Pharmaceutical Scientists (AAPS) annual meeting. November 6-10, 1994, San Diego, California. Abstracts. PMID- 7991498 TI - The imp in the bottle. PMID- 7991500 TI - [Violence, hate for foreigners and hostility to foreign visitors]. PMID- 7991501 TI - [The foreign evil]. AB - The strange as well as the criminal may serve to maintain a person's psychohygiene. They help to take the burden of internal psychological conflicts from the individual's shoulders, but at the same time confine his personal growth and his ability to become aware of his own dark sides. PMID- 7991502 TI - ["I came as a stranger, will leave as a stranger." From alienation to hostility to foreigners in the young generation]. AB - After a historical review of the discussion of the concept of strangeness and alienation since the beginning of the 19th century, the question of the background of the current discussion of "the alien" arises. The assumption is that the experience of strangeness and self-alienation took a qualitative and quantitative leap at the point in technological development when the dialectic between human and machine was resolved in favor of the machine's domination, and when the "mega-machine" made the end of the human species conceivable and probable. Findings from empirical research on children and youth support this assumption. The causes are traced why the younger generation in particular is affected by the structural violence of strangeness that permeates all areas of life. Its inflating influence on the development of the ego and self is depicted. In accordance with the assumption, hostility toward and hatred of foreigners are to be grasped as symptoms of a loss of identity, caused by experiences of alienation deeper and more comprehensive than current societal triggers reveal. PMID- 7991503 TI - ["I am estranged, just as I am." Migration experience, ego identity and neurosis]. AB - Some specific psychic phenomena which can occur in overcoming the migration process are discussed with reference to case studies. The possibility of a derailed and chaotic communication is shown. The change of socio-cultural membership can destabilize the ego and ego-identity and lead to transculturally generated unconsciousness. Symptoms of angst, or neurotic symptoms can result if pre-formed unconscious conflicts represent too great a threat to the weakened ego. For the child's ego these burdens can pose threats to the psychological maturation. The therapeutic goal is to restore ego-stability and narcissictic stability, as well as the development of a new psycho-social identity. This is possible if the patient in psychoanalysis experiences a responsive opposite, so that the disrupted inter- connections between the life-history, the various social super-ego structures, norms and contradictions can be named and understood. PMID- 7991504 TI - [Male adolescence, hatred for foreigners and the self-repair function exemplified by juvenile right extremist skinheads]. AB - Restructuring the personality, developing a new we-feeling, coping with drive thrusts and ego-syntonically reorganizing infantile conflicts are key developmental functions during adolescence. Some characteristics of male adolescence explain why especially male teen-agers are susceptible to joining right-wing extremist groups ready to use violence. The surroundings of right-wing extremist violence offers specific stabilizations which support the adolescent configuration of the enlarged self but as the same time they also lead to deformations of the personality. Establishing a greater self by ideology, self reparative transformation of self hatred to xenophobia, masking the personality and the regression of sexual desire to the desire of violence are consequences of processes of adaption and assimilation as described in cases of serious inner or outer threats. PMID- 7991505 TI - ["I am Dr. Germany." Right radical fantasies as disguised communication in psychoanalytic therapy of an adolescent patient]. AB - Using the analytic psychotherapy of a teenager as an example the readiness for right-wing extremist identifications during adolescence is described. The author evaluates which specific therapeutic interventions triggered the right-wing extremist fantasies of the patient in the treatment situation using Robert Langs's communicative theory as a guideline. The fantasies can be seen as enciphered messages with which the adolescent reacts to the therapist. In conclusion the author points out the biographical and developmental aspects of the patient's "Germany" imago. PMID- 7991506 TI - Prenatal sonographic detection of intra-abdominal extralobar pulmonary sequestration: report of three cases and literature review. AB - Three cases of intra-abdominal extralobar pulmonary sequestration detected antenatally by ultrasound are reported. One case was associated with a large left diaphragmatic hernia. Sonographically, all the cases were found in the left supra renal region presenting as a well-defined echogenic mass with cystic hypoechoic areas. The condition should be considered in the differential diagnosis of all antenatally detected upper abdominal echogenic masses, particularly when associated with a diaphragmatic hernia. Postnatal ultrasound-guided fine needle aspiration biopsy in one case yielded respiratory type epithelium and this procedure could provide a reasonably confident diagnosis of the lesion. PMID- 7991507 TI - Results from a reference laboratory for prenatal diagnosis of sickle cell disorders in Cuba. AB - A nationwide programme for the prevention of sickle cell (SS and SC) disorders was initiated in Cuba in 1983. Couples at risk were identified by screening pregnant women and the partners of those who carry an abnormal haemoglobin, followed by genetic counselling and the offer of prenatal diagnosis. Prenatal diagnosis was performed in one laboratory, which had carried out 1068 prenatal tests for Hb SS and SC disorders by the end of 1992. The centralization of the service has permitted rapid identification and resolution of problems. PMID- 7991508 TI - Body stalk anomaly associated with maternal cocaine abuse. AB - A case of body stalk anomaly diagnosed prenatally by ultrasound during the 24th week of pregnancy in a cocaine abusing mother is presented. Accurate visualization of the fetal organs was difficult due to the severe oligohydramnios caused by premature rupture of membranes, probably related to the cocaine use. The sonographic findings were an omphalocoele, fetal attachment to the placenta, kyphoscoliosis, and absence of a floating umbilical cord. The prenatal diagnosis of the syndrome and the possible relationship with cocaine abuse are discussed. PMID- 7991509 TI - Prenatal diagnosis and long survival of Fryns' syndrome. AB - We report on a case of Fryns' syndrome diagnosed prenatally in a woman with no family history of this disorder. A computerized database was used for the differential diagnosis. Intensive perinatal care resulted in prolonged survival, which is unusual in individuals with Fryns' syndrome. This case provides further delineation of the developmental course in patients with this condition. PMID- 7991510 TI - Cystic adenomatoid malformation of the lung: prenatal diagnosis and outcome. AB - During an 8-year period (1984-1992), we made the ultrasonographic diagnosis of cystic adenomatoid malformation (CAM) of the lung in 58 fetuses at 17-39 weeks' gestation. We reviewed the records of these fetuses and combined the data from 74 cases reported in the literature to determine the incidence of the different types of CAM, associated malformations, and outcome. The lesions were macrocystic in 78 (59 per cent) and microcystic in 54 (41 per cent) of the cases. CAM was left-sided in 51 per cent, right-sided in 35 per cent, and bilateral in 14 per cent of the fetuses. In 15 (11 per cent) of the fetuses there were additional malformations and 57 (43 per cent) were hydropic. The pregnancy was electively terminated in 44 (33 per cent) of the cases, including all those with bilateral CAM. There were six (5 per cent) intrauterine deaths, five in association with hydrops, and one with growth retardation and heart defect. Of the 82 (62 per cent) infants that were liveborn, 21 (26 per cent) died in the neonatal period, 15 before and six after surgery. Of the 61 survivors, 16 (26 per cent) did not require surgery. In the 88 cases where the pregnancy was not terminated, survival was better if the CAM was macrocystic (74 per cent versus 58 per cent for microcystic), if there was no hydrops (92 per cent versus 21 per cent for hydrops), and if the amniotic fluid volume was normal or decreased (82 per cent versus 53 per cent for polyhydramnios). PMID- 7991511 TI - Karyotype abnormalities in fetuses diagnosed as abnormal on ultrasound before 20 weeks' gestational age. AB - This study examined rates of karyotype abnormalities in fetuses diagnosed by ultrasound as abnormal before 20 weeks' gestational age and which prompted a follow-up amniocentesis or chorionic villus sampling. Those diagnosed before 20 weeks were compared with those diagnosed at or after 20 weeks. A retrospective study identified ultrasonographically abnormal fetuses in whom karyotyping had been undertaken, 306 fetuses before 20 weeks' gestational age and 241 after. Isolated malformations before 20 weeks had, on average, an 18 per cent risk of karyotype abnormality, compared with 20 per cent later. Specific rates were calculated; for example, heart abnormality was associated with karyotype abnormality in 7 per cent of cases before 20 weeks and in 14 per cent later. Multiple malformations and karyotype abnormalities were found together in 28 per cent of fetuses prior to 20 weeks and in 33 per cent of the older fetuses. Specific associations included nuchal oedema and trisomy 21 in 21 per cent of fetuses before 20 weeks. No karyotype abnormalities were found in fetuses diagnosed with choroid plexus cysts. An overview of trisomies in Victoria, in 1991, showed that 50 per cent of trisomy 18, 42 per cent of trisomy 13, and 9.5 per cent of trisomy 21 cases were identified by ultrasound in women less than 37 years of age. Another 28.6 per cent of trisomy 21 fetuses were detected in women of advanced maternal age who underwent amniocentesis or chorionic villus sampling, making a total of 38.1 per cent of trisomy 21 that were detected prenatally.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7991512 TI - Prenatally diagnosed non-immune hydrops caused by congenital transient leukaemia. AB - Congenital transient leukaemia (CTL) is a haematological disorder characterized by proliferation of myeloblasts within the bone marrow and peripheral blood of affected newborns. Infants with Down syndrome are most frequently affected and although the disorder can result in fetal death due to hydrops, it typically resolves spontaneously after birth. We present a case of prenatally diagnosed fetal hydrops accompanied by splenomegaly and an enlarged, echogenic liver in a fetus identified with CTL after birth. PMID- 7991513 TI - Gorlin syndrome (naevoid basal cell carcinoma syndrome): prenatal detection in a fetus with macrocephaly and ventriculomegaly. AB - The Gorlin (naevoid basal cell carcinoma) syndrome is an autosomal dominant disorder consisting principally of naevoid basal cell carcinomas, odontogenic keratocysts, skeletal abnormalities, and intracranial calcification. We report the prenatal detection of the Gorlin syndrome by ultrasonography in a fetus with macrocephaly and mild ventriculomegaly. PMID- 7991514 TI - The imprecision in rates of Down syndrome by 1-year maternal age intervals: a critical analysis of rates used in biochemical screening. AB - Current algorithms to determine eligibility for prenatal cytogenetic diagnostic services depend critically on the accuracy and precision of the underlying rates of cytogenetic abnormality used in the calculations. We examine the maternal age specific rates of Down syndrome livebirths in eight studies of European-origin populations, pooled rates from which are widely used for baseline calculations in biochemical screening. These studies vary significantly in such factors as methods of ascertainment of cases, likelihood of complete ascertainment, and methods of correction, if any, for underascertainment. Restriction of analysis to those two studies among the eight whose methods suggest the greatest likelihood of complete ascertainment for Down syndrome generates rates significantly higher than those in widespread use. Confidence intervals about previously reported and currently derived rates indicate that even with large-scale data, there is considerable residual uncertainty in derived rates. PMID- 7991515 TI - Fetal ear measurements in the prenatal detection of trisomy 21. AB - Although prominent fetal nuchal folds, short long bones, echogenic bowel, and renal pelviectasis have been shown to be associated with trisomy 21, none has acceptable diagnostic efficacy. Diminished fetal ear lengths measured by ultrasound have recently been reported as yet another potential morphological marker for the prenatal detection of trisomy 21. To investigate this further, we measured ear lengths and widths of normal (n = 107) and trisomy 21 (n = 25) second-trimester formalin-preserved fetuses. The normal ear growth characteristics are described and compared with those of trisomy 21 fetuses. The normal fetal ear shape, not unlike that of the neonates, manifested a marked variation. When the ear lengths and widths were regressed against gestational age, the slopes of the regression lines for the two groups were found to be different (P < 0.001). However, despite the statistically significant difference between the ear sizes of normal and trisomy 21 fetuses, the wide range of normal variation seen at each gestational age means that the fetal ear measurements are not diagnostically helpful. PMID- 7991516 TI - Late-onset isolated cystic hygroma: the obstetrical significance, management, and outcome. AB - We add two cases of prenatally diagnosed late-onset isolated cystic hygroma to the eight cases reported previously in the English literature. The obstetrical significance, management, and outcome of this entity are reviewed. A retrospective study of late-onset isolated cystic hygromas delivered in one medical centre between 1978 and 1992 was made. The medical records of these newborns served as the basis of the present report. A Medline search of the English literature was carried out. Over a period of 15 years, we observed 11 cases of late-onset congenital isolated cystic hygroma, two of whom had prenatal sonographic diagnosis. In one case, a Caesarean section was performed due to a huge lesion. All cases underwent surgical excision with a favourable outcome. Of the eight prenatally diagnosed cases reported previously, one died at bith due to inability to ventilate and two required a tracheostomy. Late-onset isolated cystic hygroma should be differentiated from the early-onset nuchal cystic hygroma. The differential diagnosis is important, as late-onset isolated cystic hygroma does not require any prenatal intervention, but special awareness during labour and Caesarean section in extreme cases. Transport to a perinatal centre with expert neonatal, respiratory, and paediatric surgical care is recommended. The prognosis in general is favourable. PMID- 7991517 TI - Fetal hypothyroidism as a complication of amiodarone treatment for persistent fetal supraventricular tachycardia. AB - We present a case of persistent fetal supraventricular tachycardia where transplacental and direct fetal treatment with amiodarone caused an iatrogenic hypothyroidism. This condition was successfully managed with the intra-amniotic instillation of 250 micrograms of L-thyroxine weekly, for 3 weeks. A male infant was delivered at 32 weeks by Caesarean section. The neonatal electrocardiogram showed Wolf-Parkinson-White (WPW) syndrome, which was controlled by digoxin alone. Thyroid function normalized quickly and the baby is developing normally. PMID- 7991518 TI - Prenatal sonographic appearance of foramina parietalia permagna. AB - Foramina parietalia permagna (FPP) is an extremely uncommon congenital defect, inherited as an autosomal dominant condition. Its characteristics are two symmetrical orifices in the parietal bones (not of fixed size) on both sides of the midline. This defect does not affect either the psychic or the physical development of the affected person. This paper describes the sonographic appearance of FPP in utero as an enlargement of the posterior fontanelle. PMID- 7991519 TI - Prenatal ultrasound diagnosis of rhizomelic chondrodysplasia punctata in a primigravida. AB - Rhizomelic chondrodysplasia punctata (RCDP) is a sublethal autosomal recessive disorder characterized by skeletal dysplasia, microcephaly, mental retardation, congenital cataracts, joint contractures, skin changes, and failure to thrive. Prenatal ultrasound diagnosis has been reported during the second trimester of pregnancy. Prenatal diagnosis is also possible from the first trimester onwards by demonstration of peroxisomal dysfunction in cultured chorionic villous or amniotic fluid cells. In all cases reported hitherto, the prenatal diagnosis was established after the birth of a previous affected child. In contrast to these studies in pregnant multiparous women at risk for RCDP, we report on the first case of prenatal ultrasound diagnosis of RCDP at 19 weeks' gestation in a primigravida. In addition, a complex cardiac malformation associated with hypoplasia of the thymus (DiGeorge anomaly) is described. PMID- 7991520 TI - p53 gene mutation in female genital tract carcinosarcomas (malignant mixed mullerian tumors): a clinicopathologic study of 74 cases. AB - Mutations of the p53 suppressor gene are involved in carcinogenesis by inactivating p53 protein (p53P), which is involved in normal cell growth control. Mutant p53P, detectable by immunohistochemistry due to longer half-life as compared to wild-type, is a marker for p53 gene mutation. Seventy-four female genital tract carcinosarcomas (FGTCSs) (41 of the heterologous type exhibiting 33 rhabdomyosarcomatous, 13 chondrosarcomatous, one osteosarcomatous, and one liposarcomatous component) were stained using two commercially available monoclonal antibodies: p53P, clone DO7 (p53P-DO7) and p53P, Ab-6 (p53P-P6). p53P DO7 and p53P-P6 stained 33 and 36, respectively, of 56 endometrial, 8 of 11 ovarian, 2 of 5 cervical, and 2 of 2 fallopian tube carcinosarcomas. Considering all 74 FGTCSs, p53P-DO7 and p53P-P6 stained both the carcinomatous component (CC) and the sarcomatous component (SC) in 46% and 54%, the CC only in 9.5% and 8.1%, and the SC only in 5.4 and 2.7%, respectively. The two antibodies for p53P showed the following concordance for staining of FGTCSs (either CC or SC or both) (p53P DO7/p53P-P6): +/+, 58%; +/-, 1.3%; -/+, 6.7%; -/-, 34%. p53P immunoreactivity was not associated with histological features or grade of the CC or SC. Clinical follow-up was available in 72 cases, which showed 48.5% and 70.8% of patients recurred or died of disease by 12 and 80 months, respectively. 20.8% of patients were disease-free after 19 to 307 months of follow-up (median, 62; mean, 92). The remaining 8.4% of patients were disease-free but had insufficient follow-up (< 1 year).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7991521 TI - c-erbB-2 oncoprotein expression and amplification in pleomorphic adenoma and carcinoma ex pleomorphic adenoma: relationship to prognosis. AB - The c-erbB-2 protooncogene has been shown to be overexpressed and/or amplified in carcinomas of the breast, ovary, pancreas, and other organs. Several studies of human breast carcinoma noted an association of c-erbB-2 overexpression and amplification with poor prognosis. Recent studies have demonstrated c-erbB-2 protein expression in a variety of salivary gland neoplasms, most notably pleomorphic adenoma (PA), carcinoma ex pleomorphic adenoma (CAexPA), and adenocarcinoma. In this study, we analyzed c-erbB-2 expression in 15 PAs and 13 CAexPAs, using immunohistochemistry. In addition, differential polymerase chain reaction was used to evaluate c-erbB-2 gene amplification in these tumors. Low level c-erbB-2 immunoreactivity was detected in three of 15 PAs. Among the CAexPAs, low-, intermediate-, and high-level immunoreactivity was seen in two, three, and two cases, respectively. The only cases showing c-erbB-2 amplification were the two CAexPA cases with high-level immunoreactivity. Based on statistical analysis of the 10 CAexPA patients with known outcome, no significant association of prognosis with c-erbB-2 expression or amplification was apparent. PMID- 7991522 TI - Composite cutaneous T-cell lymphoma and small B-cell lymphocytic lymphoma: morphologic, immunologic, and molecular genetic documentation of concurrent lymph node involvement. AB - Synchronous cutaneous T-cell lymphoma and low-grade B-cell lymphoproliferative disorders have rarely been reported in the same patient. Coexpression of each phenotype in the same lymph node has not, to our knowledge, been previously documented. We describe an 86-year-old man with chronic pruritus and erythroderma and recent-onset peripheral lymphadenopathy and lymphocytosis. Lymph node biopsy provided morphological and immunohistochemical evidence of concurrent small B lymphocytic lymphoma and small pleomorphic T-cell lymphoma. Immunophenotyping of nodal lymphocytes demonstrated two distinct clones: IgM-kappa B-cells with CD5 positivity and CD7 negative T-helper cells. Both immunoglobulin (heavy and light chains) and T-cell receptor (beta I and beta II) gene rearrangements were detected by Southern blot analysis of the lymph node. In contrast, the immunophenotype of lymphocytes from peripheral blood and bone marrow was exclusively that of T-helper cells with atypical CD7 deletion. Electron microscopic examination of circulating lymphocytes revealed small cerebriform Sezary cells. This case demonstrates that small lymphocytic lymphoma may coexist intranodally with cutaneous T-cell lymphoma as a unique form of composite T- and B-cell lymphoma. PMID- 7991523 TI - Geographical pathology profile of AIDS in Puerto Rico: the first decade. AB - Postmortem histopathological changes in 100 adult patients with AIDS who died in Puerto Rico from 1982 to 1991 were studied and tabulated. Modes of HIV transmission were reviewed. Patient ages ranged from 21 to 60 yr. Gender composition for the patient group was 83 men (average age, 35 yr) and 17 women (average age, 39 yr). Sixty-eight of the patients were injecting-drug users, 20 were homosexual and bisexual men, seven were women who had had heterosexual contact with men at risk for HIV, and one was a man who had had heterosexual contact with prostitutes. Only one case was linked to transfusions of blood. Twenty-seven men and seven women were serologically tested for antibodies and all were HIV seroreactive. The most common causes of infection and the frequency of each were as follows: Pneumocystis carinii in 49 patients; cytomegalovirus in 43; Toxoplasma gondii in 30; Candida species in 24; Histoplasma capsulatum in 18; Mycobacterium species in 14; Cryptococcus species in eight; and Strongyloides stercoralis in six patients. Infection by Schistosoma mansoni (10 patients) was considered incidental because this trematode is endemic in Puerto Rico. The lung was the organ most frequently infected by a single microorganism: Pneumocystis carinii affected 49 patients. However, Cryptococcus species was the microorganism that infected more body systems: 20 different organs in eight patients. Nineteen patients had microglial nodular encephalitis, 86 patients had lymphocyte depletion in the spleen, and 58 had lymphocyte depletion in lymph node tissue. Twenty-seven men had testicular maturation arrest and variable germ cell loss. Three patients had malignant lymphoma, and two had Kaposi's sarcoma.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7991524 TI - A method of correcting DNA ploidy measurements in tissue sections. AB - A new method of performing DNA ploidy measurements in tissue sections using image cytometry is described. The method involves an image processing "object" filtering operation to remove cut and overlapping nuclei, and DNA correction of larger nuclei for the part of the DNA cut away. The methodology of the technique is developed in detail, and the results of testing using sections of rat liver are presented. The results indicated reliable correction of DNA ploidy histograms to reconstruct the polyploid nature of this material. The sensitivity of the material to sectioning thickness errors and methods to overcome this were shown, along with an example of its use on prostate bioptic gun tissue sections. PMID- 7991525 TI - The value of multiple fluid specimens in the cytological diagnosis of malignancy. AB - Multiple fluid specimens of a patient are often received in the cytology laboratory. Both clinicians and pathologists question the optimal number of specimens required to detect a malignancy. We reviewed the computerized cytology files at Boston's Beth Israel Hospital from 1988 to 1991 to identify patients with two or more specimens from the same anatomic site. Two hundred and fifteen patients with a total of 570 specimens were identified. Before December 19, 1990, two direct smears were examined per fluid sample. After December 19, 1990, two direct smears and two cytospin preparations were examined. Medical records of patients without a positive diagnosis of cytology were reviewed. Overall, a cytological diagnosis of malignancy was made on at least one specimen for 55 patients (26%). The first positive diagnosis was made on the initial specimen in 36 patients (65%), on the second in 15 patients (27%), the third in three patients (5%), and the fifth in one patient (2%). For those specimens prepared with the two techniques described above (two direct and two concentrated smears), the first positive diagnosis was made on the initial specimen in 89% of the cases. Medical record review uncovered 55 additional patients who had clinical evidence of malignancy. Of these, 22 (40%) had at least one suspicious diagnosis of their fluid specimens. The first suspicious diagnosis was made with three or fewer specimens in all 22 patients. The majority of malignant effusions are detected with two specimens. Examination of more than three specimens is of little value. Multiple preparatory, especially concentration, techniques may increase the probability of detecting malignancy in one specimen. PMID- 7991526 TI - Fourier transform infrared microspectroscopy used to identify foreign materials related to breast implants. AB - Clinically useful methods to identify and document the presence of foreign material in tissues surrounding breast implants are needed. Fourier transform infrared microspectroscopy is an ideal technique for examining tissue for the presence of implantable biomaterials. Because the spectroscopy is microscopically guided, the pathologist is assured that the obtained spectrum is from the region of interest in a tissue section. Scanning electron microscopy yields elemental data but cannot be used to identify compounds. Because each compound has a unique spectrum by Fourier transform infrared microspectroscopy, the spectrum obtained enables identification of the various foreign materials observed by light microscopy in tissues surrounding breast implants. Histopathology from implant capsules demonstrating a silicone gel-filled implant, a saline-filled textured implant, a polyurethane foam-covered gel-filled implant, a Dacron fixation patch, and a paraffin injection granuloma are presented with corresponding Fourier transform infrared microspectroscopy spectra. PMID- 7991527 TI - Comparative image cytometric DNA ploidy of liver cell dysplasia and hepatocellular carcinoma. AB - Large-cell liver cell dysplasia (LCD), suggested to be a preneoplastic change that progresses to hepatocellular carcinoma (HCC), has a reported frequency of DNA aneuploidy by flow cytometry intermediate between that of nonneoplastic liver (0%) and HCC (80%). We assessed DNA ploidy by image cytometry of Feulgen-stained 5-microns sections of 30 livers with LCD and of 60 HCCs (29 with LCD in adjacent nonmalignant liver). All 30 LCDs were aneuploid, 27 (90%) of which were multiploid--11 (41%) with hyperdiploid and hypertetraploid peaks. Forty-eight (80%) HCCs were aneuploid; in nine of 20 (42%) with a hyperdiploid peak, a hyperdiploid peak was also present in the LCDs, but in none was there less than 0.24 between DNA indices. Besides the 12 (20%) diploid HCCs, a diploid peak was present in four heterogenous, three multiploid, and six HCCs with two phenotypes and two genotypes, one of which was diploid. One aneuploid/hyperdiploid peak in each of 22 nonneoplastic and 24 cirrhotic livers did not have a corresponding LCD or HCC aneuploid peak. These data do not suggest that dysplastic hepatocytes form a single mutant clone that progresses to HCC. PMID- 7991528 TI - Pulmonary hypertension and HIV infection: new observations and review of the syndrome. AB - This report describes the case of a 14-yr-old hemophiliac who died of complications of primary pulmonary hypertension. He was infected with the human immunodeficiency virus. The autopsy disclosed that he also had membranoproliferative glomerulonephritis type III and hepatic cirrhosis, both clinically unsuspected. This is the second report describing the association of membranoproliferative glomerulonephritis type III and primary pulmonary hypertension in an HIV-infected patient and the first to consider cirrhosis as a possible additional element of the syndrome. PMID- 7991529 TI - Chronic hepatitis: morphology and nomenclature. PMID- 7991531 TI - "Skinny lips". PMID- 7991530 TI - Correspondence re: J.P. Veinot, H.D. Tazelaar, W.D. Edwards, and T.V. Colby. Mesothelial/monocytic incidental cardiac excrescences: cardiac MICE. Mod Pathol 7:9-16, 1994. PMID- 7991532 TI - Correspondence re: S. Sandhyamani. Vascular lesions in an autopsy study. Mod Pathol 6:333, 1993. PMID- 7991533 TI - Latent capacities for gametogenic cycling in the semelparous invertebrate Nereis. PMID- 7991534 TI - The amygdala complex: multiple roles in associative learning and attention. AB - Although certain neurophysiological functions of the amygdala complex in learning seem well established, the purpose of this review is to propose that an additional conceptualization of amygdala function is now needed. The research we review provides evidence that a subsystem within the amygdala provides a coordinated regulation of attentional processes. An important aspect of this additional neuropsychology of the amygdala is that it may aid in understanding the importance of connections between the amygdala and other neural systems in information processing. PMID- 7991535 TI - Latent capacities for gametogenic cycling in the semelparous invertebrate Nereis. AB - Most nereid polychaetes are strictly semelparous, a single episode of reproduction being invariably followed by death. Endocrine manipulation in Nereis diversicolor by the regular implantation of cerebral ganglia from immature donors unveils characteristics associated with a capacity to engage in repeated gametogenic cycling. Such manipulation permits full maturation of the gametes but blocks spawning. Gamete resorption then leads on to another bout of gametogenesis and a new cohort of gametes is formed. The neurosecretory system adopts a cyclical pattern of activity, which parallels that of gametogenesis. Repair and maintenance of the soma continue throughout sexual maturation, as shown by the persistence of feeding and the capacity for regenerative segment proliferation. In consequence, life is extended apparently indefinitely. These latent capacities are reminiscent of features of iteroparous life histories, characterized by repeated breeding, and are postulated to be vestiges of an iteroparous ancestry. They also constitute a preadaptation for iteroparity and reveal how readily a reversal to this condition could occur. The study suggests that reproductive strategies may be unexpectedly labile in even their most fundamental aspects. PMID- 7991536 TI - Fluctuation analysis of motor protein movement and single enzyme kinetics. AB - We studied fluctuations in the displacement of silica beads driven by single molecules of the motor protein kinesin, moving under low mechanical loads at saturating ATP concentrations. The variance in position was significantly smaller than expected for the case of stepwise movement along a regular lattice of positions with exponentially distributed intervals. The small variance suggests that two or more sequential processes with comparable reaction rates dominate the biochemical cycle. The low value is inconsistent with certain recently proposed thermal ratchet models for motor movement as well as with scenarios where the hydrolysis of a single ATP molecule leads to a cluster of several steps. Fluctuation analysis is a potential powerful tool for studying kinetic behavior whenever the output of a single enzyme can be monitored. PMID- 7991537 TI - Retrotransposons in the flanking regions of normal plant genes: a role for copia like elements in the evolution of gene structure and expression. AB - The wx-K mutation results from the insertion of a copia-like retrotransposon into exon 12 of the maize waxy gene. This retrotransposon, named Hopscotch, has one long open reading frame encoding all of the domains required for transposition. Computer-assisted database searches using Hopscotch and other plant copia-like retroelements as query sequences have revealed that ancient, degenerate retrotransposon insertions are found in close proximity to 21 previously sequenced plant genes. The data suggest that these elements may be involved in gene duplication and the regulation of gene expression. Similar searches using the Drosophila retrotransposon copia did not reveal any retrotransposon-like sequences in the flanking regions of animal genes. These results, together with the recent finding that reverse-transcriptase sequences characteristic of copia like elements are ubiquitous and diverse in plants, suggest that copia-like retrotransposons are an ancient component of plant genomes. PMID- 7991538 TI - Identification of a 50-kDa systemin-binding protein in tomato plasma membranes having Kex2p-like properties. AB - A protein of 50-kDa (SBP50) was identified in plasma membranes of tomato leaves which resembles proteases of the family of Kex2p-like prohormone convertases. To our knowledge, proteases of this class have not been reported in plants previously. A biotinylated derivative of systemin, the 18-aa polypeptide inducer of proteinase inhibitors in tomato and potato leaves, was bound by SBP50 with high specificity. When a systemin derivative was labeled with biotin at residue 8 and with [35S]methionine at position 15, the biotin moiety but not the radioactive label was bound by SBP50. At least 4 aa from the C terminus that included [35S]methionine were missing, indicating that proteolytic cleavage had occurred. Whereas residues in systemin most important for binding SBP50 appear to be located in the N-terminal half of the molecule, amino acids crucial for proteinase inhibitor induction are located within the C terminus. The residues important for binding include a cleavage site for furin, a member of the family of Kex2p-like prohormone-processing enzymes. Processing of systemin at the predicted furin cleavage site was confirmed in vitro. An antiserum against a Kex2p-like protease from Drosophila inhibited binding of biotinylsystemin to SBP50 and recognized a protein of about 60 kDa in Western blot analyses of tomato plasma membrane proteins. The data suggest a possible role for a membrane bound, furin-like protease in the mechanism of defense gene signaling by systemin. PMID- 7991539 TI - Interspecific transfer of mitochondrial genes in fungi and creation of a homologous hybrid gene. AB - In eukaryotes, horizontal gene transfer is a rare event. Here we show that the mitochondrial genome of a lower fungus, Allomyces macrogynus, has an extra DNA segment not present in a close relative, Allomyces arbusculus. This insert consists of the C terminus of a foreign gene encoding a subunit of the ATP synthetase complex (atp6) plus an open reading frame encoding an endonuclease. The inserted atp6 portion is fused in phase to the resident gene, resulting in expression of a hybrid atp6 gene and the displacement of the original C-terminal atp6 region. We present evidence that this insertion may have been acquired by interspecific transfer and we discuss the possible role of the endonuclease in this process. PMID- 7991540 TI - Type 1/type 2 cytokine modulation of T-cell programmed cell death as a model for human immunodeficiency virus pathogenesis. AB - In vitro T-cell receptor-induced programmed cell death in both activated T cells from human immunodeficiency virus-seronegative (HIV-) donors and resting T cells from HIV+ donors was substantially influenced by cytokines. Addition of exogenous recombinant "type 1" lymphokines interferon gamma and interleukin 2 (IL-2), as well as the macrophage-produced IL-12, which favor cell-mediated T-cell responses, blocks both systems of T-lymphocyte programmed cell death. In contrast, the "type 2" lymphokines IL-4 and IL-10, which favor antibody responses, either had no effect or enhanced these systems of in vitro T-cell programmed cell death. A role for endogenously produced cytokines was suggested by the inhibition of T-cell receptor-mediated death by antibodies against IL-4 and IL-10 and its enhancement by anti-IL-12 in cultures containing monocytes. These results demonstrate that the functional properties of type 1 and type 2 cytokine classes may be further extended to include their effects on T-cell programmed cell death and their possible role in the pathogenesis of HIV infection. PMID- 7991541 TI - Observation of binding and polymerization of Fur repressor onto operator containing DNA with electron and atomic force microscopes. AB - The Fur (ferric uptake regulation) protein is a global regulator that, in the presence of Fe2+, represses the expression of a number of iron-acquisition genes and virulence determinants such as toxins. Dark-field electron microscopy of positively stained Fur-DNA complexes in addition to atomic force microscopy allowed direct visualization of Fur interactions with the regulatory regions of aerobactin and hemolysin operons and provided complementary information about the structure of the complexes. According to the DNA used and the protein/DNA ratio, Fur binding to DNA results in partial or total covering of the fragments, indicating that the protein initiates polymerization along the DNA molecules at specific sites. Negative staining of Fur-DNA complexes revealed a well-ordered structure of the polymer suggesting a helical arrangement. Local rigidification of the DNA molecules resulting from Fur binding could be involved in the repression process. PMID- 7991542 TI - Molecular cloning of a myosin I beta isozyme that may mediate adaptation by hair cells of the bullfrog's internal ear. AB - The internal ear's sensory receptor, or hair cell, responds when stimuli deflect its mechanoreceptive hair bundle. As a hair cell adapts to sustained stimulation, mechanical adjustments within the bundle reset its position of sensitivity. Because several lines of experimentation suggest that a form of myosin I mediates adaptation, we endeavored to clone cDNAs encoding this motor molecule. By using degenerate oligonucleotide primers based upon the deduced amino acid sequence for mammalian myosin I beta, we performed reverse transcription and polymerase chain reactions (PCRs) to produce a candidate cDNA from polyadenylylated mRNA isolated from the frog's brain. The resultant product was used to probe a cDNA library, from which were isolated clones encoding an approximately 119-kDa isozyme of myosin I beta. PCR amplification disclosed the presence of mRNA encoding the same isozyme in tissue from the bullfrog's sacculus, an organ of the internal ear. When expressed as a bacterial fusion protein, a domain from the tail region of this form of myosin I was recognized by monoclonal antibodies that react with myosin I in hair bundles. This cloned approximately 119-kDa isozyme of myosin I is accordingly a candidate to be the motor molecule responsible for the adaptation of mechanoelectrical transduction by hair cells. PMID- 7991543 TI - Solution scattering from 50S ribosomal subunit resolves inconsistency between electron microscopic models. AB - Models of the 50S ribosomal subunit from electron microscopy on isolated particles and on ordered sheets display significantly different features. A model of the shape of the native Escherichia coli 50S subunit in solution and of its RNA-rich core at 4-nm resolution has been produced by using methods for joint interpretation of x-ray and neutron small-angle scattering data obtained by contrast variation. The good agreement between the shape of the entire 50S subunit and the electron microscopic models of isolated particles and between the RNA-rich core and the model obtained from ordered sheets leads to the conclusion that the latter, which is based on the subjective contouring of density maps, is heavily biased toward the RNA. PMID- 7991544 TI - Nuclear accumulation of interferon gamma. AB - Examination of the interferon gamma (IFN-gamma) amino acid sequence revealed two conserved basic amino acid clusters similar to the prototype nuclear localization signal. We followed the fate of cell surface receptor-bound IFN-gamma in murine leukemia L1210 cells. A time- and temperature-dependent accumulation of murine IFN-gamma in the cell nucleus could be demonstrated by autoradiography and indirect immunofluorescence after the rapid isolation of nuclei. Human IFN-gamma was also internalized and translocated to the nucleus of murine L1210 cells transfected with and expressing the human IFN-gamma receptor, but it appeared to be retained by the nucleus only transiently. IFN-gamma molecules chemically crosslinked to their cell surface receptor remain capable of being translocated to the nucleus even as part of a receptor-ligand complex. Thus, the bipartite nuclear localization signal sequence appears to be functional and suggests that nuclear targeting could participate in IFN-gamma signal transduction. PMID- 7991546 TI - Light-induced isomerization causes an increase in the chromophore tilt in the M intermediate of bacteriorhodopsin: a neutron diffraction study. AB - Bacteriorhodopsin (BR) was regenerated with two selectively deuterated retinals, one with 11 deuterons in the beta-ionone ring (D11) and the other with 5 deuterons (D5) at the end of the polyene chain closest to the Schiff base at carbon atoms C-14, C-15, and C-20. Both label positions (centers of deuteration) were obtained from difference Fourier maps of projections onto the plane of the membrane by neutron diffraction at 90 K, both in the light-adapted ground-state BR568 and in the photocycle intermediate M412. To retard the decay of M412, purple membrane films were soaked in 0.1 M or 1 M guanidine hydrochloride at pH 9.6. M412 was produced by illuminating oriented membrane films at physiological temperature (278 K), followed by rapid cooling to 90 K in the absence of light. The results show that in the projected structure the ring position is unaltered during the transition from BR568 to M412, whereas the position of the D5 label shifts by 1.4 +/- 0.9 A toward the ring. The shortened interlabel distance in the projected structure for the M412 state implies that as a result of the all trans/13-cis isomerization, the C-5 to C-13 part of the polyene chain tilts out of the plane of the membrane toward the cytoplasm by about 11 degrees +/- 6 degrees. Pairwise comparison of data sets with the same retinal for the two photocycle states M412 and BR568 leads to four difference-density maps for the protein, which are in agreement with previous work. They show changes in the protein density near helices G and F. PMID- 7991545 TI - Targeted mutation in the neurotrophin-3 gene results in loss of muscle sensory neurons. AB - Neurotrophin 3 (NT-3) is one of four related polypeptide growth factors that share structural and functional homology to nerve growth factor (NGF). NT-3 and its receptor, called neurotrophic tyrosine kinase receptor type 3 (Ntrk3; also called TrkC), are expressed early and throughout embryogenesis. We have inactivated the NT-3 gene in embryonic stem (ES) cells by homologous recombination. The mutated allele has been transmitted through the mouse germ line, and heterozygote intercrosses have yielded homozygous mutant newborn pups. The NT-3-deficient mutants fail to thrive and exhibit severe neurological dysfunction. Analysis of mutant embryos uncovers loss of Ntrk3/TrkC-expressing sensory neurons and abnormalities at early stages of sensory neuronal development. NT-3-deficient mice will permit further study of the role of this neurotrophin in neural development. PMID- 7991547 TI - Casein kinase II specifically nucleotidylylates in vitro the amino acid sequence of the protein encoded by the alpha 22 gene of herpes simplex virus 1. AB - An earlier report has shown that eight viral proteins with a common amino acid sequence (R/P)RA(P/S)R are nucleotidylyated in vitro by nuclear extracts from cells infected with herpes simplex virus 1. One, the product of the alpha 22 gene, is nucleotidylylated in the absence of viral proteins made late in infection. A chimeric protein (GST22P) consisting of amino acids 50-200 of the alpha 22 coding sequence fused to the C terminus of the glutathione S-transferase was nucleotidylylated by enzymes in nuclear extracts of infected or mock-infected cells and also by a casein kinase II enzyme purified from the sea star. The enzyme did not nucleotidylylate common casein kinase II substrates (casein, phosvitin) and the reaction was inhibited by heparin. The results are consistent with the hypothesis that nucleotidylylation of the eight viral proteins involves casein kinase II. PMID- 7991548 TI - Isolation of unknown genes from human bone marrow by differential screening and single-pass cDNA sequence determination. AB - A cDNA sequencing project was initiated to characterize gene expression in human bone marrow and develop strategies to isolate novel genes. Forty-eight random DNAs from total human bone marrow were subjected to single-pass DNA sequence analysis to determine a limited complexity of mRNAs expressed in the bone marrow. Overall, 8 cDNAs (17%) showed no similarity to known sequences. Information from DNA sequence analysis was used to develop a differential prescreen to subtract unwanted cDNAs and to enrich for unknown cDNAs. Forty-eight cDNAs that were negative with a complex probe were subject to single-pass DNA sequence determination. Of these prescreened cDNAs, the number of unknown sequences increased to 23 (48%). Unknown cDNAs were also characterized by RNA expression analysis using 25 different human leukemic cell lines. Of 13 unknown cDNAs tested, 10 were expressed in all cell types tested and 3 revealed a hematopoietic lineage-restricted expression pattern. Interestingly, while a total of only 96 bone marrow cDNAs were sequenced, 31 of these cDNAs represent sequences from unknown genes and 12 showed significant similarities to sequences in the data bases. One cDNA revealed a significant similarity to a serine/threonine-protein kinase at the amino acid level (56% identity for 123 amino acids) and may represent a previously unknown kinase. Differential screening techniques coupled with single-pass cDNA sequence analysis may prove to be a powerful and simple technique to examine developmental gene expression. PMID- 7991549 TI - Stepwise immortalization and transformation of adult human prostate epithelial cells by a combination of HPV-18 and v-Ki-ras. AB - Recent investigations have shown the presence of ras gene mutations and human papillomavirus (HPV) DNA in prostate carcinomas. In the present study, secondary adult human prostatic epithelial cells, upon transfection with a plasmid containing the entire HPV-18 genome, acquired an indefinite life-span in culture but did not undergo malignant conversion. Subsequent infection of these immortalized cells with the Kirsten murine sarcoma virus, which contains an activated Ki-ras oncogene, induced morphological transformation that led to the acquisition of neoplastic properties. These findings demonstrate the malignant transformation of adult human prostate epithelial cells in culture by a combination of viral oncogenes and the successive roles of HPV infection and Ki ras activation in a multistep process responsible for prostate carcinogenesis. PMID- 7991550 TI - Human cytomegalovirus latent infection of granulocyte-macrophage progenitors. AB - We have investigated the interaction of human cytomegalovirus (CMV) with cultured primary granulocyte-macrophage progenitors, a suspected natural site of viral latency, and have established conditions for latent infection and reactivation in this cell population. Progenitor cells from human fetal liver or bone marrow maintained a CD14+, CD15+, CD33+ cell surface phenotype during propagation in suspension culture. Exposure to human CMV did not reduce growth or alter the phenotype of these cells during a 4-week culture period. Viral replication was not detectable in these cells, although viral DNA, as measured by PCR analysis, persisted in a high proportion of cultured cells in the absence of delayed early (beta) gene expression. Viral gene expression was restricted such that only ie1 region transcripts were detected by PCR analysis of cDNA, and these transcripts were estimated to be present in no less than 2-5% of latently infected cells. Most of these transcripts remained unspliced, a result that strikingly contrasts with the splicing pattern normally seen during viral replication in permissive cells. Latent virus reactivated after prolonged, 16- to 21-day cocultivation of infected granulocyte-macrophage progenitors with permissive cells, results that support a role for the myelomonocytic cell population as a biological reservoir of latent human CMV and suggest that these cells may be the source of CMV DNA PCR positive monocytes found in the peripheral blood of healthy carriers. PMID- 7991551 TI - Inducible phosphorylation of I kappa B alpha is not sufficient for its dissociation from NF-kappa B and is inhibited by protease inhibitors. AB - The ubiquitous transcription factor NF-kappa B is regulated by its cytoplasmic inhibitor I kappa B. A variety of cellular stimuli cause the dissociation of NF kappa B from I kappa B, allowing NF-kappa B to translocate to the nucleus and regulate gene expression. Although the activation of NF-kappa B in vivo is associated with the phosphorylation and degradation of I kappa B alpha, it has remained unclear how each of these events contributes to this process. Recently, studies utilizing protease inhibitors have suggested that the proteolysis of I kappa B alpha is a necessary event in the activation of NF-kappa B. We demonstrate in this study that these and an additional protease inhibitor also completely repress inducible phosphorylation of I kappa B alpha. This surprising result suggests a more complex role of proteases in NF-kappa B activation. In addition, data presented here indicate that many of these inhibitors also directly modify NF-kappa B and inhibit its DNA binding activity. Due to the pleiotropic effects of these protease inhibitors, it is difficult to conclude from their use how I kappa B alpha phosphorylation and degradation contribute to NF-kappa B activation. In the present study, a more direct approach demonstrates that phosphorylation of I kappa B alpha alone is not sufficient for NF-kappa B activation. PMID- 7991552 TI - The Gal(alpha 1-4)Gal-specific tip adhesin of Escherichia coli P-fimbriae is needed for pyelonephritis to occur in the normal urinary tract. AB - Nonobstructive acute pyelonephritis in humans is most often caused by P fimbriated Escherichia coli. P-fimbriae are heteropolymeric fibers carrying a Gal(alpha 1-4)Gal-specific PapG adhesin at its distal end. The pyelonephritic strain DS17 expresses P-fimbriae from a single gene cluster. A mutant strain, DS17-8, which expresses P-fimbriae tacking the PapG adhesin, was constructed by allelic replacement introducing a 1-bp deletion early in the papG gene. In cynomolgus monkeys, DS17 and DS17-8 were equally able to cause bladder infection, whereas only the wild-type strain DS17 could cause pyelonephritis as monitored by bacteriological, functional, and histopathological criteria. Since DS17, but not DS17-8, adheres to renal tissue, these data underscore the critical role of microbial adherence to host tissues in infectious disease and strongly suggest that the PapG tip adhesin of P-fimbriae is essential in the pathogenesis of human kidney infection. PMID- 7991553 TI - Expression of the allatostatin gene in endocrine cells of the cockroach midgut. AB - Cockroach allatostatins are neuropeptides that have been isolated from the brain of Diploptera punctata and shown to inhibit juvenile hormone production by the corpora allata. Enzyme-linked immunoassay and immunocytochemistry with antisera to two allatostatins, ASB2 (AYSYVSEYKRLPVYNFGL-NH2) and ASAL (APSGAQRLYGFGL-NH2), revealed that allatostatins were located not only in the insect brain but also in several peripheral tissues including the cockroach midgut and hindgut. Allatostatin-like immunoreactivity was found in nerve fibers of the stomatogastric nervous system as well as in intrinsic endocrine cells of the midgut. Midgut extracts were shown to be biologically active in an allatostatin bioassay and to contain several allatostatin-like peptides, including the octadecapeptide ASB2, which was identified by mass spectrometry following HPLC purification. Reverse transcription of brain mRNA followed by PCR with degenerate oligonucleotides for ASB2 and ASAL yielded a 338-bp fragment of the allatostatin gene that encoded six allatostatins. In situ hybridization with this probe confirmed that an allatostatin gene is expressed in intrinsic endocrine cells of the midgut. Reverse transcription of midgut mRNA followed by PCR and sequencing of the product revealed that the same gene is expressed in the midgut and in the brain. Allatostatins are thus an example of insect "brain-gut peptides" and we suggest that their function may not be restricted to the regulation of juvenile hormone production. PMID- 7991554 TI - Mutagenic potency of exocyclic DNA adducts: marked differences between Escherichia coli and simian kidney cells. AB - A single-stranded shuttle vector containing a single 3,N4-etheno-2'-deoxycytidine (epsilon dC) or 1,N2-(1,3-propano)-2'- deoxyguanosine (PdG) DNA adduct was used to investigate translesional DNA synthesis in Escherichia coli and simian kidney (COS) cells. The presence of either exocyclic adduct was associated with reduced numbers of transformants. In E. coli, this inhibitory effect could be overcome partially by irradiating cells with UV light before transformation. Translesional synthesis past both exocyclic lesions was accompanied by targeted mutations. For PdG, the primary mutagenic events observed in both hosts were PdG-->T transversions; in preirradiated E. coli, PdG-->A transitions were also observed. The targeted mutation frequency for single-stranded DNA that contained PdG was 100% in nonirradiated E. coli, 68% in preirradiated cells, and 8% in COS cells. In contrast, the targeted mutation frequency for single-stranded DNA that contained epsilon dC was 2% in nonirradiated E. coli, 32% in preirradiated cells, and 81% in COS cells. The primary mutations generated by epsilon dC in both E. coli and COS cells were epsilon dC-->A and epsilon dC-->T base substitutions. These observations appear to reflect the variable specificity of DNA replication complexes in incorporating bases opposite certain adducts. We conclude that DNA synthesis past the same DNA adduct can have strikingly different consequences in bacteria and mammalian cells, underscoring the importance of establishing the intrinsic mutagenic potential of DNA adducts in mammalian cells. PMID- 7991555 TI - Protein footprinting by the combined use of reversible and irreversible lysine modifications. AB - A two-step lysine-modification procedure has been devised to chemically footprint protein surfaces involved in macromolecular interactions. A protein tagged at one particular end, in the free state or in a complex, is first treated lightly with a reversible lysine-modifying reagent. The protein is then unfolded and treated extensively with an irreversible lysine reagent to block those lysines that did not react previously; next, the first lysine modification is reversed, and a lysine-specific endoproteinase is used to cleave the tagged polypeptide at the deblocked lysines. Separation of the proteolytic products by size and identification of the tagged fragments map the positions of these lysines. In this procedure, the reversible lysine reagent serves as the chemical footprinting agent, as cleavage of the polypeptide ensues only at the sites of reaction with this reagent. Lysines involved in macromolecular contacts are identified from differences in proteolytic patterns of the tagged protein when the first lysine modification is done with the protein in the free form and in a complex. Application of the method to vaccinia virus topoisomerase identifies a number of lysines that are involved in its binding to DNA. PMID- 7991556 TI - Binding of TFIID to the CYC1 TATA boxes in yeast occurs independently of upstream activating sequences. AB - Functional transcription initiation complexes can be assembled in vitro without the aid of regulatory factors that bind to upstream activating sequences. However, promoters that lack upstream activating sequences are transcribed poorly if at all in vivo, suggesting that regulatory factors are necessary for the assembly of transcription initiation complexes in cells. To test this possibility, we asked whether the general transcription factor TFIID can bind to a promoter in yeast that lacks upstream activating sequences and is transcriptionally inactive. Analysis of an inactive CYC1 core promoter by high resolution genomic footprinting revealed efficient binding of TFIID to either of two TATA box elements. Addition of a heat shock element rendered this promoter highly responsive to induction of transcription by heat shock but did not alter the TATA box footprints in the core promoter. Inactivation of all but one TATA box by site-directed mutagenesis did not prevent TFIID from binding to the remaining wild-type TATA box independently of regulatory sequences. These results indicate that upstream regulatory factors are not required for the in vivo binding of TFIID to the CYC1 promoter and that binding of TFIID to DNA is not necessarily a rate-limiting step in the activation of transcription in cells. Differences in chromatin structure may account for why regulatory transcription factors are required for the binding of TFIID to some promoters but not to others. PMID- 7991557 TI - Differentiation-dependent expression of the Na+/glucose cotransporter (SGLT1) in LLC-PK1 cells: role of protein kinase C activation and ongoing transcription. AB - We examined changes in the mRNA level of SGLT1, a Na+/glucose cotransporter, by the differentiation status of LLC-PK1 renal epithelial cells. Proliferating (undifferentiated) cells revealed no detectable SGLT1 mRNA by Northern blot analysis. However, when cells became confluent and differentiated into polarized monolayers, there was an abrupt appearance of the SGLT1 mRNA. When confluent (differentiated) cells were dedifferentiated by reseeding at a subconfluent density, SGLT1 mRNA levels decreased quickly to nondetectable levels (t1/2 = 1.5 h), while the mRNA levels of gamma-glutamyltranspeptidase, another differentiation marker, decreased only slowly (t1/2 > 40 h). This decrease in SGLT1 mRNA was completely blocked by H-7, a protein kinase inhibitor. Since protein kinase C was highly activated in the undifferentiated cells and treatment of differentiated cells with a phorbol ester also induced quick and complete loss of SGLT1 mRNA (t1/2 = 1.5 h) but not of gamma-glutamyltranspeptidase mRNA, protein kinase C activation appears to be involved in the dedifferentiation induced decrease in SGLT1 mRNA. Although the phorbol ester-induced decrease in the SGLT1 mRNA level was blocked completely by inhibition of transcription, inhibitors of translation blocked the decrease in mRNA levels only partially. PMID- 7991558 TI - Coatomer-rich endoplasmic reticulum. AB - We identify in normal cells the existence of two distinct sites of the transitional endoplasmic reticulum (ER), one housing the Sec23p protein complex (the classical transitional element), the other the coatomer protein complex (the coatomer-rich ER). Experimental conditions that reduce transport from the ER to the Golgi complex lead to the overexpression of this newly defined coatomer-rich ER. PMID- 7991560 TI - Initiation of meiotic recombination is independent of interhomologue interactions. AB - In yeast meiosis, crossing-over between homologues is dependent upon double strand breaks. We demonstrate that the occurrence of these breaks is independent of pairing between homologues by showing that they occur with normal frequency, timing, and position in the absence of a homologue. This observation supports models that view double-strand breaks as initiating events and crossing-over as a consequence of repair of these breaks. PMID- 7991559 TI - Initiation of recombination in Saccharomyces cerevisiae haploid meiosis. AB - In most eukaryotes during prophase I of meiosis, homologous chromosomes pair and recombine by coordinated molecular and cellular processes. To directly test whether or not the early steps of the initiation of recombination depend on the presence of a homologous chromosome, we have examined the formation and processing of DNA double-strand breaks (DSBs, the earliest physical landmark of recombination initiation) in various haploid Saccharomyces cerevisiae strains capable of entering meiosis. We find that DSBs occur in haploid meiosis, showing that the presence of a homolog is not required for DSB formation. DSBs occur at the same positions in haploid and diploid meioses. However, these two types of meiosis exhibit subtle differences with respect to the timing of formation and levels of DSBs. In haploid meiosis, a slower rate of DSB formation and a reduction in the frequency of DSB (at one of the three sites analyzed) were observed. These results might indicate that interactions between homologs play a role in the formation of meiotic DSBs. Furthermore, haploid strains exhibit a pronounced delay in the disappearance of meiotic DSBs compared to diploid strains, which suggests that sister chromatid interactions for DSB repair are inhibited in haploid meiosis. PMID- 7991561 TI - Directing transcription of an RNA polymerase III gene via GAL4 sites. AB - A yeast chimeric RNA polymerase III transcription system was constructed to explore the ordered, multistep process of gene activation in vivo. A promoter deficient U6 RNA gene harboring GAL4-binding sites could be reactivated by fusing the GAL4 DNA-binding domain to components of the general transcription factor TFIIIC (tau) or TFIIIB. Expression of chimeric tau 138 or tau 131 (but not tau 95) subunits activated transcription from GAL4-binding sites located at various positions, including upstream of or within the gene. The function(s) of the B block binding domain of TFIIIC was provided by the fused GAL4-(1-147) domain. The GAL4-(1-147)-TFIIIB70 fusion protein acted at a distance like an activator of transcription. In contrast, none of the 10 different GAL4-(1-147)-polymerase subunit fusions was able to induce transcription, suggesting that RNA polymerase recruitment is not sufficient to initiate transcription. PMID- 7991562 TI - Rapid detection of homologous recombinants in nontransformed human cells. AB - Gene targeting is a technique by which a preselected site in the genome of a living cell can be modified by inserting, deleting, or exchanging DNA sequences. The application of this technology to cells with a limited life-span, such as nontransformed human somatic cells, requires the development of simplified and efficient procedures to allow the isolation of correctly modified cells from the much larger pool of random integrants. The current study describes the development of a widely applicable strategy for detecting homologous recombinants in human cells by using an ELISA-based screen. When this system is used accurately targeted clones can be detected with high efficiency as soon as 14 days following transfection. Data are presented demonstrating the utility of this detection system in isolating targeted recombinants at the beta 2-microglobulin locus in both human retinal pigmented epithelial cells and human keratinocytes. PMID- 7991563 TI - Lymphocyte proliferation in mice congenitally deficient in T-cell receptor alpha beta + cells. AB - In mice and humans, T cells are characterized on the basis of T-cell receptor (TcR) expression and divided into the major TcR alpha beta + and minor TcR gamma delta + populations. TcR alpha beta + cells are considered to be the primary regulators of the immune response, whereas the function of TcR gamma delta + cells is unclear. Mice congenitally deficient in TcR alpha beta-expressing cells provide an ideal model for analyzing the independent in vivo function of TcR gamma delta + cells in the absence of TcR alpha beta + cells. Here we report that lymphoid organs in TcR alpha mutant mice undergo substantial enlargement after being challenged by environmental antigens. This organ expansion can be attributed in part to increases in the relative proportions and absolute numbers of TcR gamma delta + cells, but an expansion of the recently described TcR beta + alpha - population also has a role. The expansion of the TcR gamma delta + population is polyclonal, as evidenced by the usage of multiple gamma and delta variable chain segments. Furthermore, a substantial proportion of the cells appears to be activated and these activated cells express surface activation markers. The results clearly demonstrate that TcR gamma delta + cells proliferate independently in response to a broad spectrum of challenges. Moreover, since the expansion of the lymphoid tissues and the TcR gamma delta + cell population is excessive relative to that seen in wild-type animals, one role of TcR alpha beta + cells is directly or indirectly to limit the responses of the other lymphoid components. PMID- 7991564 TI - An ADP-ribosyltransferase as a potential target for nitric oxide action in hippocampal long-term potentiation. AB - Recent studies of long-term potentiation (LTP) in the CA1 region of the hippocampus have demonstrated that nitric oxide (NO) may be involved in some forms of LTP and have suggested that postsynaptically generated NO is a candidate to act as a retrograde messenger. However, the molecular target(s) of NO in LTP remain to be elucidated. The present study examined whether either of two potential NO targets, a soluble guanylyl cyclase or an ADP-ribosyltransferase (ADPRT; EC 2.4.2.31) plays a role in LTP. The application of membrane-permeant analogs of cGMP did not produce any long-lasting alterations in synaptic strength. In addition, application of a cGMP-dependent protein kinase inhibitor did not prevent LTP. We found that the CA1 tissue from hippocampus possesses an ADPRT activity that is dramatically stimulated by NO and attenuated by two different inhibitors of mono-ADPRT activity, phylloquinone and nicotinamide. The extracellular application of these same inhibitors prevented LTP. Postsynaptic injection of nicotinamide failed to attenuate LTP, suggesting that the critical site of ADPRT activity resides at a nonpostsynaptic locus. These results suggest that ADP-ribosylation plays a role in LTP and are consistent with the idea that an ADPRT may be a target of NO action. PMID- 7991566 TI - Interplay between excited-state intramolecular proton transfer and charge transfer in flavonols and their use as protein-binding-site fluorescence probes. AB - A comparative study is presented of competitive fluorescences of three flavonols, 3-hydroxyflavone, 3,3',4',7-tetrahydroxyflavone (fisetin), and 4'-diethylamino-3 hydroxyflavone (DHF). The normal fluorescence S1-->S0 (400-nm region) is largely replaced by the proton-transfer tautomer fluorescence S'1-->S'0 in the 550-nm region for all three of the flavonols in aprotic solvents at room temperature. For DHF in polar solvents the normal fluorescence becomes a charge-transfer fluorescence (460-500 nm) which competes strongly with the still dominant proton transfer fluorescence (at 570 nm). In protic solvents, and at 77 K, the interference with intramolecular hydrogen bonding gives rise to greatly enhanced normal fluorescence, lowering the quantum yield of proton-transfer fluorescence. The utility of DHF as a discriminating fluorescence probe for protein binding sites is suggested by the strong dependence of the charge-transfer fluorescence on polarity of the environment and by various static and dynamic parameters of the charge-transfer and proton-transfer fluorescence which can be determined. PMID- 7991565 TI - Rab geranylgeranyl transferase catalyzes the geranylgeranylation of adjacent cysteines in the small GTPases Rab1A, Rab3A, and Rab5A. AB - Rab proteins are Ras-related small GTPases that are geranylgeranylated on cysteine residues located at or near their C termini. They differ from other geranylgeranylated small GTPases in several important respects. (i) Most Rab proteins contain two adjacent cysteine residues within one of the following C terminal sequence motifs: -XXCC, -XCXC, or -CCXX; (ii) a Rab protein that ends in a -XCXC motif has been shown to be geranylgeranylated on both adjacent cysteine residues; and (iii) Rab proteins are substrates of a unique Rab-specific geranylgeranyltransferase. Whether this enzyme catalyzes the geranylgeranylation of both cysteines is unknown. We addressed this question by direct structural analysis of in vitro prenylated proteins. We incubated recombinant Rab geranylgeranyltransferase, Rab escort protein, and [1-3H]geranylgeranyl pyrophosphate with recombinant wild-type Rab1A (-XXCC), Rab3A (-XCXC), or Rab5A ( CCXX) and treated each labeled protein with trypsin. We then analyzed the resulting peptides by HPLC and electrospray mass spectrometry and found that for each protein both C-terminal adjacent cysteines were geranylgeranylated. These results indicate that Rab geranylgeranyltransferase/Rab escort protein catalyzes the geranylgeranylation of both cysteines in Rab proteins with three distinct C terminal motifs and suggest that other Rab proteins with these motifs may be similarly modified. PMID- 7991567 TI - The mitochondrial outer membrane protein Mas22p is essential for protein import and viability of yeast. AB - We have cloned the gene encoding the protein Mas22p, which spans the outer membrane of yeast mitochondria. Cells that completely lack Mas22p are inviable. The plasmid-borne MAS22 gene suppresses several defects resulting from the deletion of one or more of the mitochondrial protein import receptors. Defects of Mas20p-deficient cells are explained by the reduced level of Mas22p in these mutants. Mas22p has one acidic domain in the cytosol and a second acidic domain in the mitochondrial intermembrane space. We suggest that these domains of Mas22p on either side of the outer membrane function as a relay system for transferring the basic targeting sequences of precursor proteins into the mitochondria. PMID- 7991568 TI - Cloning of a human gene involved in cytochrome oxidase assembly by functional complementation of an oxa1- mutation in Saccharomyces cerevisiae. AB - The yeast nuclear gene OXA1 is essential for cytochrome oxidase assembly, so that a null mutation in the OXA1 gene leads to complete respiratory deficiency. We have cloned by genetic selection a human OXA1 (OXA1Hs) cDNA that complements the respiratory defect of yeast oxa1 mutants. The deduced sequence of the human protein shares 33% identity with the yeast OXA1 protein. The OXA1Hs cDNA corresponds to a single and relatively highly expressed gene. Oxygen consumption measurements and cytochrome absorption spectra show that replacement of the yeast protein with the human homolog leads to the correct assembly of cytochrome oxidase, suggesting that the proteins play essentially the same role in both organisms. PMID- 7991569 TI - Evolution of mobile group I introns: recognition of intron sequences by an intron encoded endonuclease. AB - Mobile group I introns are hypothesized to have arisen after invasion by endonuclease-encoding open reading frames (ORFs), which mediate their mobility. Consistent with an endonuclease-ORF invasion event, we report similarity between exon junction sequences (the recognition site for the mobility endonuclease) and intron sequences flanking the endonuclease ORF in the sunY gene of phage T4. Furthermore, we have demonstrated the ability of the intron-encoded endonuclease to recognize and cleave these intron sequences when present in fused form in synthetic constructs. These observations and accompanying splicing data are consistent with models in which the invading endonuclease ORF is provided safe haven within a splicing element. In turn the intron is afforded immunity to the endonuclease product, which imparts mobility to the intron. PMID- 7991570 TI - Bone marrow declines as a site of B-cell precursor differentiation with age: relationship to thymus involution. AB - The rearrangement of immunoglobulin genes in B-lymphocyte precursors requires the expression of the recombination activating genes (Rag), which leads to the generation of a highly diverse B-cell repertoire. We can use the level of Rag-1 mRNA in the bone marrow as an index of its capacity to support the maturation of B lymphocytes as all detectable bone marrow Rag-1 mRNA is expressed by B-cell precursors. In mouse bone marrow, Rag-1 mRNA increases during the first 2 months of life to reach its maximal level at 2 months of age. This level is maintained until 5 months of age and thereafter declines to a minimum level by 10 months of age. Thus, bone marrow Rag-1 mRNA is highest at the time when thymic function is maximal in euthymic mice. An association between thymic activity and bone marrow Rag-1 gene expression was supported by showing a low level of bone marrow Rag-1 mRNA in athymic nude mice at an age when this gene is maximally expressed in euthymic mice. Another characteristic of B cells in nude mice is their preferential rearrangement of diversity region (D)-proximal heavy-chain variable region (VH) genes. We demonstrated that injection of syngeneic splenic T cells into nude mice not only stimulates an increase in Rag-1 mRNA in their bone marrow B-cell precursors but also restores their random use of VH genes. Most interestingly, injection of supernatant medium from phytohemagglutinin-activated splenic T-cell cultures from young euthymic mice also induces both Rag-1 mRNA in bone marrow B-cell precursors and random use of VH genes. These findings suggest that thymic function can regulate both Rag-1 gene expression and VH gene use by bone marrow B-cell precursors. PMID- 7991571 TI - Excessive production of amyloid beta-protein by peripheral cells of symptomatic and presymptomatic patients carrying the Swedish familial Alzheimer disease mutation. AB - The 39- to 43-amino acid amyloid beta-protein (A beta), which is progressively deposited in cerebral plaques and blood vessels in Alzheimer disease (AD), is secreted by cultured human cells during normal metabolism. In studies of cell lines transfected with beta-amyloid precursor protein (beta APP) cDNAs, the beta APP mutation K670N/M671L found in a Swedish familial AD (FAD) pedigree has previously been shown to cause a marked augmentation of A beta secretion. Here, we have conducted blinded analyses of beta APP metabolism in primary skin fibroblasts from affected members of the Swedish FAD pedigree and their unaffected siblings or spouses. These fibroblasts continuously secrete a homogenous population of A beta molecules starting at Asp-1 (D672 of beta APP). We found a consistent and significant approximately 3-fold elevation of A beta release from all biopsied skin fibroblasts bearing the FAD mutation. No significant alterations of other metabolic derivatives of beta APP were detected. The elevated A beta levels were found in cells from both patients with clinical AD and presymptomatic subjects. Thus, A beta overproduction in this FAD pedigree is not a secondary event but is consistent with a causal role in the development of the disease. Increased A beta secretion can begin many years prior to onset of symptoms, even in peripheral tissues, indicating that it does not require preexisting neural abnormalities. PMID- 7991572 TI - Prostaglandin D2-sensitive, sleep-promoting zone defined in the ventral surface of the rostral basal forebrain. AB - The site of action for the sleep-promoting effect of prostaglandin (PG) D2 was extensively examined in the brain of adult male rats (n = 231). PGD2 was administered at 100 pmol/0.2 microliter per min for 6 hr (2300-0500 hr) through chronically implanted microdialysis probes or infusion cannulae. Among the administrations of PDG2 by dialysis probes (n = 176), only those (n = 8) to a ventro-rostral part of the basal forebrain by the probes implanted on the midline consistently increased slow-wave sleep (SWS), by 51 +/- 6 min (mean +/- SEM) above the baseline value (111 +/- 11 min). Since this area is separated by a cleft into right and left regions, the results were interpreted to mean that, through this cleft, PGD2 diffused in the subarachnoid space over the adjacent ventral surface, where it had the effect of promoting sleep. When PGD2 was directly infused into the subarachnoid space (n = 55), extraordinary increases exceeding 90 min were consistently attained for the SWS at sites located between 0.5 and 2 mm rostral to the bregma and between 0 and 1.2 mm lateral to the midline defined according to the stereotaxic coordinates adopted from the brain atlas of Paxinos and Watson [Paxinos, G. & Watson, C. (1986) The Rat Brain in Stereotaxic Coordinates (Academic, San Diego)]. Thus, we demarcated a "PGD2 sensitive, sleep-promoting zone" within this region in the ventral surface of the rostral basal forebrain. During the bilateral infusion of PGD2 into the subarachnoid space of this zone, the hourly mean SWS level of the nocturnal animals (n = 6) in the night reached the maximum at the second hour of the infusion period; this maximum hourly SWS level, corresponding to the daytime level of the same animals, lasted until the end of PGD2 infusion. PMID- 7991573 TI - Fialuridine accumulates in DNA of dogs, monkeys, and rats following long-term oral administration. AB - Accumulation of the antiviral nucleoside analogue fialuridine (FIAU; 1-(2'-deoxy 2'-fluoro-beta-D-arab-inofuranosyl-5-iodouracil) in genomic DNA was examined with a modified version of a recently developed RIA for FIAU. DNA was obtained from tissues of dogs administered FIAU at 0, 1, 2, or 3 mg/kg of body weight per day for 90 days, monkeys administered FIAU at 0 or 25 mg/kg per day for 30 days, and rats administered FIAU at 0, 255, or 510 mg/kg per day for 70 days. FIAU incorporation was observed in all species. In the rat, FIAU was incorporated into DNA of all tissues examined, with highest concentrations in the liver followed by jejunum, spleen, and heart. FIAU was also incorporated into sperm DNA. Incorporation rates were as high as 11,000 pmol of FIAU per mumol of thymidine or 1 FIAU molecule per 90 thymidine molecules. In dogs and rats, the extent of incorporation was dose-dependent. Across species, FIAU concentrations in DNA were not singly dependent on the total dose administered but also may have been dependent on the duration of exposure. These studies show that FIAU accumulates to high concentrations in genomic DNA of liver as well as other tissues during chronic oral administration and suggest that net accumulation of FIAU in DNA may be a critical step in FIAU-induced toxicity. PMID- 7991574 TI - Targeted gene replacement demonstrates that myristoyl-CoA: protein N myristoyltransferase is essential for viability of Cryptococcus neoformans. AB - Cryptococcus neoformans is a major cause of systemic fungal infection in immunocompromised patients. Myristoyl-CoA:protein N-myristoyltransferase (Nmt) catalyzes the transfer of myristate (C14:0) from myristoyl-CoA to the N-terminal glycine of a subset of cellular proteins produced during vegetative growth of C. neoformans. A Gly487-->Asp mutation was introduced into C. neoformans NMT by targeted gene replacement. The resulting strains are temperature-sensitive myristic acid auxotrophs. They are killed at 37 degrees C when placed in medium lacking myristate and, in an immunosuppressed animal model of cryptococcal meningitis, are completely eliminated from the subarachnoid space within 12 days of initial infection. C. neoformans and human Nmts exhibit differences in their peptide substrate specificities. These differences can be exploited to develop a new class of fungicidal drugs. PMID- 7991575 TI - Pharmacological and biochemical demonstration of the role of cyclooxygenase 2 in inflammation and pain. AB - Nonsteroidal antiinflammatory drugs (NSAIDs) are widely used for the treatment of inflammatory diseases, but significant side effects such as gastrointestinal erosion and renal damage limit their use. NSAIDs inhibit the enzyme cyclooxygenase (COX), which catalyzes the conversion of arachidonic acid to prostaglandins (PGs) and thromboxane. Two forms of COX have been identified--COX 1, which is constitutively expressed in most tissues and organs, and the inducible enzyme, COX-2, which has been localized primarily to inflammatory cells and tissues. In an animal model of acute inflammation (injection of carrageenan into the footpad), edema was produced that was associated with marked accumulation of COX-2 mRNA and thromboxane. A selective inhibitor of COX-2 (SC 58125) inhibited edema at the inflammatory site and was analgesic but had no effect on PG production in the stomach and did not cause gastric toxicity. These data suggest that selective inhibition of COX-2 may produce superior antiinflammatory drugs with substantial safety advantages over existing NSAIDs. PMID- 7991576 TI - Differentiation of receptor subtypes by thermodynamic analysis: application to opioid delta receptors. AB - The temperature dependence of the dissociation constant for the interaction of an opioid delta selective ligand and its receptor was evaluated in three tissues. The change in free energy of this interaction was similar in mouse brain, mouse spinal cord, and NG 108-15 mouse neuroblastoma-rat glioma hybrid cells (delta G(o)' = -13.44, -13.34, and -13.66 kcal.mol-1, respectively). However, the reaction was endothermic and occurred with an increase in entropy in mouse brain and NG 108-15 cells, but it was exothermic and occurred with a negligible change in entropy in mouse spinal cord. These data are consistent with the existence of multiple subtypes of opioid delta receptor, and they further suggest that the opioid delta receptor recently cloned from the NG 108-15 cell line is of the brain subtype. Subtypes of opioid delta receptors may mediate analgesia, but not side-effects, of opiates and thus could be targets for future drug design. PMID- 7991577 TI - Participation of the ascending serotonergic system in the stimulation of atrial natriuretic peptide release. AB - Results obtained in our laboratories have provided evidence for the participation of the hypothalamic atrial natriuretic peptide (ANP) neuronal system in the regulation of water and electrolyte homeostasis. The anterior ventral third ventricular (AV3V) region, a site of the perikarya of the ANP neurons, receives important afferent input from ascending serotoninergic axons. We hypothesized that the ascending serotoninergic tract might be involved in control of the liberation of ANP. Therefore, electrolytic lesions were produced in the mesencephalic dorsal raphe nucleus (DRN), the site of perikarya of serotonin (5 HT) neurons whose axons project to the AV3V region. Rats with sham lesions constituted the control group. In a second group of animals, the serotoninergic system was depleted of 5-HT by lateral ventricular administration of p chlorophenylalanine (PCPA), an amino acid that causes depletion of 5-HT from the serotoninergic neurons. Control animals were injected with an equal amount of isotonic saline. The DRN lesions induced an increase of water intake and urine output beginning on the first day that lasted for 1 week after lesions were produced. There was a concomitant sodium retention that lasted for the same period of time. When water-loaded, DRN-lesioned and PCPA-injected animals showed diminished excretion of sodium, accompanied by a decrease in basal plasma ANP concentrations, and blockade of the increase in plasma ANP, which followed blood volume expansion by intraatrial injection of hypertonic saline. The results are interpreted to mean that ascending stimulatory serotoninergic input into the ANP neuronal system in the AV3V region produces a tonic stimulation of ANP release, which augments sodium excretion and inhibits water intake. Therefore, in the absence of this serotoninergic input following destruction of the serotoninergic neurons by DRN lesions or intraventricular injection of PCPA, an antinatriuretic effect is obtained that is associated with increased drinking, either because of sodium retention per se or removal of ANP-induced inhibition of release of the dipsogenic peptide, angiotensin II. The serotoninergic afferents also play an essential, stimulatory role in volume expansion-induced release of ANP and the ensuing natriuresis. PMID- 7991578 TI - Determination of the effective charge of a protein in solution by capillary electrophoresis. AB - This paper describes two methods to estimate the effective charge of a protein in solution by capillary electrophoresis and demonstrates these methods by using representative proteins. In one method, a "charge ladder"--a series of derivatives of a protein differing by known increments of charge but differing only minimally in hydrodynamic drag--is generated by covalent modification of the epsilon-amino groups of lysines with 4-sulfophenyl isothiocyanate or acetic anhydride. In the second method, the equivalent of a charge ladder is produced by noncovalent association of a protein with differently charged ligands. Analysis of the electrophoretic mobilities of the protein and its derivatives as a function of added charge allows the effective charge to be estimated for the unmodified protein. This type of analysis permits estimation of the effective charge of a protein without knowing its composition, structure, or amino acid sequence. PMID- 7991580 TI - Topology of the RNA polymerase active center probed by chimeric rifampicin nucleotide compounds. AB - Spatial organization of the binding sites for the priming substrate, the template DNA, and the transcription inhibitor rifampicin (Rif) in Escherichia coli RNA polymerase (EC 2.7.7.6) was probed with chimeric compounds in which Rif is covalently attached to a ribonucleotide. The compounds bind to RNA polymerase in bifunctional manner and serve as substrates for RNA chain extension, yielding chains up to 8 nucleotides in length, with Rif linked to their 5' termini. These products act as potent inhibitors of normal transcription. Using the linker between the two ligands as ruler, we determined the distance between the sites for Rif and the priming nucleotide to be approximately 15 A. A reactive side group placed in the linker next to Rif crosslinks to the template strand of DNA at the -2 or -3 position of the promoter. Thus, bound Rif is juxtaposed to DNA immediately upstream of the start site, suggesting that Rif plugs the channel leading RNA out of the active center. PMID- 7991579 TI - Disruption of a topoisomerase-DNA cleavage complex by a DNA helicase. AB - The type II DNA topoisomerases are targets for a variety of chemotherapeutic agents, including the antibacterial quinolones and several families of antitumor drugs. These agents stabilize an enzyme-DNA cleavage complex that consists of the topoisomerase covalently linked to the 5' phosphates of a double-stranded DNA break. Although the drug-stabilized cleavage complex is readily reversible, it can result in cell death by a mechanism that remains uncertain. Here we demonstrate that the action of a DNA helicase can convert the cleavage complex into a nonreversible DNA break by displacing DNA strands from the complex. Formation of a nonreversible DNA break, induced by a DNA helicase, could explain the cytotoxicity of these topoisomerase poisons. PMID- 7991581 TI - Chromosome painting in plants: in situ hybridization with a DNA probe from a specific microdissected chromosome arm of common wheat. AB - We report here on the successful painting of a specific plant chromosome within its own genome. Isochromosomes for the long arm of chromosome 5 of the wheat B genome (5BL) were microdissected from first meiotic metaphase spreads of a monoisosomic 5BL line of the common wheat Triticum aestivum cv. Chinese Spring. The dissected isochromosomes were amplified by degenerate oligonucleotide-primed PCR in a single tube reaction. The amplified DNA was used as a complex probe mixture for fluorescent in situ hybridization on first meiotic metaphase spreads of lines carrying 5BL as a distinctive marker. Hybridization signals were observed, specifically, along the entire 5BL. In some of the cells, labeling was also detected in two bivalents, presumably those of the 5B "homoeologues" (partial homologues) found in common wheat (5A and 5D). The probe also revealed discrete domains in tapetal nuclei at interphase, further supporting the probe's high specificity. These data suggest that chromosome and homoeologous group specific sequences are more abundant in 5BL than genome-specific sequences. Chromosome-painting probes, such as the one described here for 5BL, can facilitate the study of chromosome evolution in polyploid wheat. PMID- 7991582 TI - Covalent catalysis in nucleotidyl transfer reactions: essential motifs in Saccharomyces cerevisiae RNA capping enzyme are conserved in Schizosaccharomyces pombe and viral capping enzymes and among polynucleotide ligases. AB - Formation of the 5' cap structure of eukaryotic mRNAs occurs via transfer of GMP from GTP to the 5' terminus of the primary transcript. RNA guanylyltransferase, the enzyme that catalyzes this reaction, has been isolated from many viral and cellular sources. Though differing in molecular weight and subunit structure, the various guanylyltransferases employ a common catalytic mechanism involving a covalent enzyme-(Lys-GMP) intermediate. Saccharomyces cerevisiae CEG1 is the sole example of a cellular capping enzyme gene. In this report, we describe the identification and characterization of the PCE1 gene encoding the capping enzyme from Schizosaccharomyces pombe. PCE1 was isolated from a cDNA library by functional complementation in Sa. cerevisiae. Induced expression of PCE1 in bacteria and in yeast confirmed that the 47-kDa Sc. pombe protein was enzymatically active. The amino acid sequence of PCE1 is 38% identical (152 of 402 residues) to the 52-kDa capping enzyme from Sa. cerevisiae. Comparison of the two cellular capping enzymes with guanylyltransferases encoded by DNA viruses revealed local sequence similarity at the enzyme's active site and at four additional collinear motifs. Mutational analysis of yeast CEG1 demonstrated that four of the five conserved motifs are essential for capping enzyme function in vivo. Remarkably, the same motifs are conserved in the polynucleotide ligase family of enzymes that employ an enzyme-(Lys-AMP) intermediate. These findings illuminate a shared structural basis for covalent catalysis in nucleotidyl transfer and suggest a common evolutionary origin for capping enzymes and ligases. PMID- 7991583 TI - Rapid humanization of the Fv of monoclonal antibody B3 by using framework exchange of the recombinant immunotoxin B3(Fv)-PE38. AB - B3(Fv)-PE38 is a recombinant single-chain immunotoxin in which the Fv region of carcinoma-specific antibody B3 is fused to a truncated form of Pseudomonas exotoxin (PE). The efficacy of monoclonal antibody B3 and B3 immunotoxins in cancer therapy and diagnosis may be limited by the human anti-mouse response. Here we describe the humanization of the Fv of B3(Fv)-PE38 by "framework exchange." The variable domains of the heavy (VH) and light (VL) chains were aligned with their best human homologs to identify framework residues that differ. Initially, 11 framework residues in VH and six in VL were changed by site specific mutagenesis to human residues and introduced simultaneously into a preassembled single-chain Fv expression cassette. Six VH and five VL residues that differ were not changed because they were buried, in the interdomain interface, or previously found to result in decreased affinity when mutated. This basic design resulted in some 20-fold loss of activity. Changing VL residues at the interdomain interfacial position 100 and at the buried position 104 to the human sequence increased the activity 8-fold. Changing VH residue at position 82b from the human sequence back to that of the mouse restored the activity 2- to 3 fold to the full binding and cytotoxic activity of the mouse sequence. Humanized B3(Fv)-PE38 lost immunogenic epitopes recognized by sera from monkeys that had been immunized with B3(Fv)-PE38. PMID- 7991584 TI - Transcription of a yeast telomere alleviates telomere position effect without affecting chromosome stability. AB - Telomeres are required for the stable maintenance of chromosomes in the yeast Saccharomyces cerevisiae. Telomeres also repress the expression of genes in their vicinity, a phenomenon known as telomere position effect. In an attempt to construct a conditional telomere, an inducible promoter was introduced adjacent to a single telomere of a chromosome such that transcription could be induced toward the end of the chromosome. Transcription toward two other essential chromosomal elements, centromeres and origins of replication, eliminates their function. In contrast, transcription toward a telomere did not affect the stability function of the telomere as measured by the loss rate of the transcribed chromosome. Transcription proceeded through the entire length of the telomeric tract and caused a modest reduction in the average length of the transcribed telomere. Transcription of the telomere substantially reduced the frequency of cells in which an adjacent URA3 gene was subject to telomere position effect. These results indicate that telomere position effect can be alleviated without compromising chromosome stability. PMID- 7991585 TI - Differences in the molecular structure of c-myc-activating recombinations in murine plasmacytomas and precursor cells. AB - The translocation of c-myc on chromosome (chr.) 15 to an immunoglobulin heavy chain switch region on chr. 12 is the critical oncogenic step in pristane-induced plasmacytoma (PCT) development in BALB/cAnPt mice. Applying a recently developed PCR method, we have been able to detect the most commonly occurring illegitimate recombinations between alpha-chain switch region (S alpha) and c-myc in preneoplastic B cells residing in mesenteric oil granuloma (OG) tissues 7-30 days postpristane. In this study, we compare the nucleotide sequences at the S alpha/c myc breaksites on both the c-myc-activating chr. 12+ and the reciprocal chr. 15- from eight transplanted PCTs, seven primary PCTs, and five OGs that contained six B-cell clones. These junction sequences revealed a remarkable diversity of S alpha/c-myc recombinations. In nine cases--four PCTs and five B-cell clones- nearly precise reciprocal exchanges with a loss of only 3-35 bp in c-myc were found. Large deletions in c-myc that removed 369-878 bp were observed in seven PCTs but not in early B cells. Duplications of c-myc ranging from 103 to 229 bp were also restricted to PCTs and noticed in four cases. Clonally related but different reciprocal recombinations, 38 bp apart on chr. 12+ and 15 bp apart on chr. 15-, were isolated from two different specimens of the same OG tissue from a BALB/c mouse 30 days postpristane. A second OG from another 30-day mouse yielded four recombinational fragments--two clonally related chr. 12(+)-specific fragments and two chr. 15(-)-specific fragments--one of which carried a 143-bp insertion of a microsatellite at the breaksite. We suggest that the initial recombinational break-point regions between S alpha and c-myc in plasmacytoma precursor cells at the time of immunoglobulin heavy-chain switching are intrinsically labile and characterized by a persisting instability of c-myc, which can result in large secondary deletions of c-myc. PMID- 7991586 TI - Identification of a melanosomal membrane protein encoded by the pink-eyed dilution (type II oculocutaneous albinism) gene. AB - The pink-eyed dilution (p) locus in the mouse is critical to melanogenesis; mutations in the homologous locus in humans, P, are a cause of type II oculocutaneous albinism. Although a cDNA encoded by the p gene has recently been identified, nothing is known about the protein product of this gene. To characterize the protein encoded by the p gene, we performed immunoblot analysis of extracts of melanocytes cultured from wild-type mice with an antiserum from rabbits immunized with a peptide corresponding to amino acids 285-298 of the predicted protein product of the murine p gene. This antiserum recognized a 110 kDa protein. The protein was absent from extracts of melanocytes cultured from mice with two mutations (pcp and p) in which transcripts of the p gene are absent or greatly reduced. Introduction of the cDNA for the p gene into pcp melanocytes by electroporation resulted in expression of the 3.3-kb mRNA and the 110-kDa protein. Upon subcellular fractionation of cultured melanocytes, the 110-kDa protein was found to be present in melanosomes but absent from the vesicular fraction; phase separation performed with the nonionic detergent Triton X-114 confirmed the predicted hydrophobic nature of the protein. These results demonstrate that the p gene encodes a 110-kDa integral melanosomal membrane protein and establish a framework by which mutations at this locus, which diminish pigmentation, can be analyzed at the cellular and biochemical levels. PMID- 7991587 TI - Incipient and overt stages of neoplastic transformation. AB - A subline of NIH 3T3 cells was developed that multiplies to low saturation density and produces no transformed foci in a standard assay at confluence if the cells had been kept in continuous exponential growth by passage at extremely low density. Repeated cycles of extended incubation at confluence result in the production of large dense foci with large increases in saturation density of the culture. I investigated the changes preceding overt transformation and the conditions that favor them by making a preliminary 2- or 3-week incubation of cells at high density in 2, 5, or 10% (vol/vol) calf serum (CS) followed by three consecutive assays at 2-week intervals, all in 2% CS. The cell counts on transfer of each consecutive assay constituted their saturation density, and staining of sister dishes exhibited transformed foci and other morphological evidence of transformation. To strengthen the significance of the observations, each CS category consisted of four separate but parallel lineages. The initial incubation in 2, 5, and 10% CS is referred to as the first-round (1 degree) assay. In the second-round (2 degrees) assay in 2% CS after the primary incubation for 2 weeks in different concentrations of CS, there were small but consistent increases in saturation density that were proportional to the CS concentration used in the first round. There were also large numbers of very light foci in the 2 degrees assay that increased in size as a function of the CS concentration used in the 1 degree assay but were uniform within each CS category. In the 3 degrees and 4 degrees successive assays, large dense foci appeared in a sporadic manner but these were also dependent on the CS concentration in the initial incubation. Cultures kept in the 1 degree assay in 5 and 10% CS for 3 weeks produced large dense foci at an earlier stage of the subsequent assays than did those kept for only 2 weeks in the 1 degree assay. The barely perceptible nature of the early morphological changes suggests an analogy to incipient neoplasia. Their graded nature, relatively high frequency, regularity of occurrence, and uniformity of appearance are characteristic of an epigenetic process, which Foulds [Foulds, L. (1969) Neoplastic Development, Vol. I (Academic, New York), preface, pp. 41-89] cited as the most plausible basis for incipient neoplasia [corrected]. In contrast, the low-frequency and sporadic occurrence of the large dense foci, which have the main features of overt neoplasia, are consistent with both genetic and epigenetic processes. PMID- 7991588 TI - Three forms of gonadotropin-releasing hormone characterized from brains of one species. AB - Most vertebrate species have more than one form of gonadotropin-releasing hormone (GnRH) in their brains, but it is not clear whether each form has a distinct function. We report that sea bream (Sparus aurata) brains have three forms of GnRH, one of which is described herein and is called sea bream GnRH (sbGnRH). The primary structures of two forms were determined by Edman degradation and mass spectral analysis. The amino acid sequence of sbGnRH is pGlu-His-Trp-Ser-Tyr-Gly Leu-Ser-Pro-Gly-NH2. The second peptide is identical to a form originally isolated from chicken brains (cGnRH-II): pGlu-His-Trp-Ser-His-Gly-Trp-Tyr-Pro-Gly NH2. cGnRH-II is the most ancient form of GnRH identified to date in jawed fish and the most prevalent form throughout the vertebrates. The third form of GnRH has previously been identified as salmon GnRH by cDNA studies and is confirmed here by chromatographic and immunological studies. Phylogenetic distribution of GnRH peptides suggests sbGnRH arose in the perch-like fish as a gene duplication of the existing cGnRH-II or salmon GnRH genes. All three identified GnRH peptides were synthesized and shown to release gonadotropin in vivo in the sea bream. The dominant form of GnRH stored in the pituitary was sbGnRH. Not only was the content of sbGnRH 500-fold greater than that of salmon GnRH but also cGnRH-II was not detected in the pituitary. The latter evidence suggests that sbGnRH is the endogenous releaser of gonadotropin II. PMID- 7991589 TI - Detection of conserved segments in proteins: iterative scanning of sequence databases with alignment blocks. AB - We describe an approach to analyzing protein sequence databases that, starting from a single uncharacterized sequence or group of related sequences, generates blocks of conserved segments. The procedure involves iterative database scans with an evolving position-dependent weight matrix constructed from a coevolving set of aligned conserved segments. For each iteration, the expected distribution of matrix scores under a random model is used to set a cutoff score for the inclusion of a segment in the next iteration. This cutoff may be calculated to allow the chance inclusion of either a fixed number or a fixed proportion of false positive segments. With sufficiently high cutoff scores, the procedure converged for all alignment blocks studied, with varying numbers of iterations required. Different methods for calculating weight matrices from alignment blocks were compared. The most effective of those tested was a logarithm-of-odds, Bayesian-based approach that used prior residue probabilities calculated from a mixture of Dirichlet distributions. The procedure described was used to detect novel conserved motifs of potential biological importance. PMID- 7991590 TI - Angiogenin promotes invasiveness of cultured endothelial cells by stimulation of cell-associated proteolytic activities. AB - Angiogenin, a potent inducer of neovascularization in the chicken chorioallantoic membrane and rabbit cornea, promotes endothelial cell invasion of Matrigel basement membrane. A transformed bovine aortic endothelial cell line, GM 7373, is 5 times more invasive when cultured in the presence of 1 microgram of bovine angiogenin per ml than in its absence. A polyclonal anti-angiogenin antibody and alpha 2-antiplasmin neutralize the effect of angiogenin, but an angiogenin binding protein (actin) does not. Further, this concentration of angiogenin induces a 14-fold increase in the cell-associated proteolytic activity of cultured endothelial cells, determined with a tissue-type plasminogen activator specific peptide as the substrate. In addition, cells cultured on a three dimensional fibrin gel in the presence of angiogenin are 3 times more capable of dissolving the gel and forming focal defects in the underlying matrix. The results indicate that angiogenin can enhance the ability of endothelial cells to digest extracellular matrix components and degrade basement membrane, thereby facilitating cell invasion and migration. Binding of angiogenin to its cell surface binding protein (actin) followed by dissociation of the angiogenin-actin complex from the cell surface and subsequent activation of tissue-type plasminogen activator/plasmin are likely steps involved in the processes of endothelial cell invasion and angiogenesis. PMID- 7991591 TI - Fractal analysis of proton exchange kinetics in lysozyme. AB - Experimental data for the exchange of protons in tritiated lysozyme is reexamined by using a fractal model. The fraction of protons unexchanged, f, is seen to follow a stretched exponential, f infinity exp[(-t/tau)alpha], in the long time limit. Data over a range of temperatures are considered, and accurate fits are obtained with a single, unadjusted scaling exponent, alpha. The time constant, tau, follows an Arrhenius law and gives an activation energy comparable to that obtained for free peptide exchange. A model is proposed where proton exchange occurs as a result of solvent reacting with protein side groups in a restricted volume surrounding the protein. Dynamic fluctuations of the protein allow the protonated groups to enter this volume. Solvent also penetrates this volume, allowing proton exchange to occur. The fluctuations of reactants in this restricted volume dominate the kinetics and result in anomalous behavior. The topology of this reaction volume can be characterized by its fractal dimension. The fractal dimension of the space excluded by the protein is equal to 3-ds, where ds is the fractal dimension of the protein surface. The dimensionality of this "reaction space" can be used to predict the value of the exponent alpha. When the problem is treated as a reaction of the type A + B-->C in a confined region, the exponent is given by alpha = (3-ds)/4. By using the value of 2.17 previously established for the surface dimension of lysozyme [Pfeifer, P., Welz, U. & Wippermann, H. (1985) Chem. Phys. Lett. 113, 535-540], a corresponding alpha of 0.21 is calculated. Data for lysozyme at six different temperatures could be accurately fit by using this unadjusted value for alpha. These results show how the surface morphology of a protein influences diffusional processes of small molecules associating with the protein. PMID- 7991592 TI - AFC1, a LAMMER kinase from Arabidopsis thaliana, activates STE12-dependent processes in yeast. AB - In the yeast Saccharomyces cerevisiae a kinase cascade activates the transcription factor STE12 leading to mating in haploid cells and pseudohyphal growth in diploid cells. To investigate related signal transduction pathways in higher plants, we have isolated a putative protein kinase gene from Arabidopsis thaliana that restores STE12-dependent functions to yeast with mutations in this signal transduction pathway. This Arabidopsis gene, AFC1, induces three STE12 dependent processes even in signal transduction-defective yeast strains: mating specific gene expression in haploid yeast, mating of haploid yeast to yield diploids, and pseudohyphal growth in diploid yeast. AFC1 has no effect on transcription of the STE12 gene and, instead, is likely to activate the STE12 protein. However, AFC1 has only limited homology to FUS3 and KSS1, the endogenous yeast kinase regulators of STE12. AFC1 is a member of a recently described CDC2 related kinase subfamily, the LAMMER kinases. A close AFC1 homolog, AFC2, lacks STE12 activation phenotypes, indicating the specificity of AFC1. The phenotypes of AFC1 in yeast provide us with tools to elucidate the role of this kinase in Arabidopsis. PMID- 7991593 TI - Cloning of ELL, a gene that fuses to MLL in a t(11;19)(q23;p13.1) in acute myeloid leukemia. AB - To characterize the functions of MLL fusion transcripts, we cloned the gene that fuses to MLL in the translocation t(11;19)(q23;p13.1). This translocation is distinct from another type of 11;19 translocation with a 19p13.3 breakpoint that results in the fusion of MLL to the ENL gene. By PCR screening of a cDNA library prepared from a patient's leukemia cells with this translocation, we obtained a fusion transcript containing exon 7 of MLL and sequence of an unknown gene. The sequence of this gene was amplified and used as a probe to screen a fetal brain cDNA library. On Northern blot analysis, this cDNA detected a 4.4-kb transcript that was abundant in peripheral blood leukocytes, skeletal muscle, placenta, and testis and expressed at lower levels in spleen, thymus, heart, brain, lung, kidney, liver, and ovary. In addition, a 2.8-kb transcript was present in peripheral blood, testis, and placenta. On "zoo blots," this gene was shown to be evolutionarily conserved in 10 mammalian species as well as in chicken, frog, and fish. We have named this gene ELL (for eleven-nineteen lysine-rich leukemia gene). A highly basic, lysine-rich motif of the predicted ELL protein is homologous to similar regions of several proteins, including the DNA-binding domain of poly(ADP-ribose) polymerase. The characterization of the normal functions of ELL as well as its altered function when fused to MLL will be critical to further our understanding of the mechanisms of leukemogenesis. PMID- 7991594 TI - Group A streptococci efficiently invade human respiratory epithelial cells. AB - Although infection by group A streptococci is a model of extracellular mucosal pathogenesis, these organisms can be associated with highly invasive infections resulting in sepsis and shock. Over the last 6 yr this species has renewed its reputation as a significant cause of sepsis and has piqued interest in the mechanism by which some strains are better able to breach mucosal barriers to gain access to the bloodstream than are others. An internalization assay was developed on the basis of resistance of intracellular streptococci to penicillin and gentamicin. Experiments showed that stationary-phase, as opposed to logarithmic-phase, bacteria are efficiently internalized and can persist in cultured human cells. Electron microscopy confirmed that streptococci were contained within intracellular vacuoles. Various strains of streptococci revealed significant differences in their capacity to be internalized. Two type M1 streptococci isolated from blood infections were internalized at frequencies equal to those reported for Salmonella and Listeria monocytogenes and greater than the frequency of a clonal variant from a case of pharyngitis. PMID- 7991595 TI - Protein domains connect cell cycle stimulation directly to initiation of DNA replication. AB - Polyoma large T antigen (LT) is the only viral gene product required for viral DNA replication. LT can be divided into two domains, one N-terminal (NT) spanning residues 1-260 and one C-terminal (CT) comprising approximately residues 264-785. NT is known to immortalize primary cells in a manner dependent on binding of pRB/p107. Here a CT construct comprising residues 264-785 was shown to have independent function in DNA replication. CT is entirely sufficient for driving viral DNA replication in vivo in growing mouse cells at a level approaching that of full-length LT. In contrast, CT is strikingly deficient for replication in serum-starved cells. However, this deficiency can be complemented by coexpression of NT. BrdUrd incorporation in transfected, starved cells showed that NT was sufficient for inducing S phase, suggesting a mechanism for complementation. By contrast, CT was unable to induce S phase when tested in the same assay. NT also promotes phosphorylation of sites in CT that are likely to be important for replication. Other DNA tumor virus gene products such as adenovirus E1A 12S and human papillomavirus 16 E7 could also complement CT for replication. Although NT, E1A 12S, and E7 all bind the retinoblastoma gene product (pRB) and p107, genetic analysis demonstrates an additional function, independent of that binding, is responsible for complementation. PMID- 7991596 TI - Interactions between saturated acyl chains confer detergent resistance on lipids and glycosylphosphatidylinositol (GPI)-anchored proteins: GPI-anchored proteins in liposomes and cells show similar behavior. AB - Proteins anchored by GPI are poorly solubilized from cell membranes by cold nonionic detergents because they associate with detergent-resistant membranes rich in cholesterol and sphingolipids. In this study, we demonstrated that cholesterol and sphingolipid-rich liposomes were incompletely solubilized by Triton X-100. GPI-anchored placental alkaline phosphatase incorporated in these liposomes was also not solubilized by cold Triton X-100. As sphingolipids have much higher melting temperatures (Tm) than cellular phospholipids, a property correlated with Tm might cause detergent inextractability. In support of this idea, we found that the low-Tm lipid dioleoyl phosphatidylcholine (DOPC) was efficiently extracted from detergent-resistant liposomes by Triton X-100, whereas the high-Tm lipid dipalmitoyl phosphatidylcholine (DPPC) was not. The fluorescence polarization of liposome-incorporated diphenylhexatriene was measured to determine the "fluidity" of the detergent-resistant liposomes. We found that these liposomes were about as fluid as DPPC/cholesterol liposomes, which were present in the liquid-ordered phase, and much less fluid than DOPC or DOPC/cholesterol liposomes. These findings may explain the behavior of GPI anchored proteins, which often have saturated fatty acyl chains and should prefer a less-fluid membrane. Therefore, we propose that acyl chain interactions can influence the association of GPI-anchored proteins with detergent-resistant membrane lipids. The affinity of GPI-anchored proteins for a sphingolipid-rich membrane phase that is not in the liquid crystalline state may be important in determining their cellular localization. PMID- 7991597 TI - Two-state transition between molten globule and unfolded states of acetylcholinesterase as monitored by electron paramagnetic resonance spectroscopy. AB - Cys-231 of Torpedo californica acetylcholinesterase (EC 3.1.1.7) was selectively labeled with the mercury derivative of a stable nitroxyl radical. In 1.5 M guanidinium chloride, this conjugate exists in a molten globule state (MG), whereas in 5 M denaturant, it is in an unfolded state (U). The transition between the two states is reversible. In the MG, the label is highly immobilized, whereas in the U, it is almost freely rotating. The clearly distinct electron paramagnetic resonance (EPR) spectra of the two states permits the study of this transition. Upon elevating the guanidinium chloride concentration, a decrease in the EPR signal of the MG occurs concomitantly with an increase in the U signal, the total intensity of the EPR spectra remaining constant. This behavior is characteristic of a two-state transition. The thermodynamic characteristics of this transition (delta G0 and m), whether estimated directly from the EPR data or from both CD and fluorescence data analyzed by assuming a two-state scheme, are in good agreement. PMID- 7991598 TI - De novo synthesis of an intron by the maize transposable element Dissociation. AB - The mechanisms by which introns are gained or lost in the evolution of eukaryotic genes remain poorly understood. The discovery that transposable elements sometimes alter RNA splicing to allow partial or imperfect removal of the element from the primary transcripts suggests that transposons are a potential and continuing source of new introns. To date, splicing events that precisely restore the wild-type RNA sequence at the site of insertion have not been detected. Here we describe alternative RNA splicing patterns that result in precise removal of a Dissociation (Ds) insertion and one copy of its eight-nucleotide host site duplication from an exon sequence of the maize shrunken2-mutabe1 (sh2-m1) mutant. In one case, perfect splicing of Ds was associated with aberrant splicing of an intron located 32 bp upstream of the insertion site. The second transcript type was indistinguishable from wild-type mRNA, indicating that Ds was spliced like a normal intron in about 2% of the sh2-m1 transcripts. Our results suggest that the transposition of Ds into sh2 in 1968, in effect, marked the creation of a new intron in a modern eukaryotic gene. The possibility of precise intron formation by a transposable element demonstrated here may be a general phenomenon of intron formation, since consensus intron splice sites can be explained by insertions that duplicate host sequences upon integration. A model is presented. PMID- 7991599 TI - (C-A)n microsatellite repeat D7S522 is the most commonly deleted region in human primary breast cancer. AB - Loss of heterozygosity in human chromosome 7q was studied to determine the location of a putative tumor suppressor gene. Twenty-six of 31 cases studied presented loss of heterozygosity at one or more loci on chromosome 7q. Eighty three percent loss of heterozygosity (in 11 informative cases) was detected by using the (C-A)n microsatellite repeat marker D7S522 at 7q31.1-7q31.2. These results suggest that a tumor suppressor gene relevant to the development of breast cancer is present in the 7q31.1-7q31.2 region, confirming our previous evidence for a tumor suppressor gene in this chromosome and frequent deletions of the long arm in human primary breast cancers. PMID- 7991600 TI - Infectious amyloid precursor gene sequences in primates used for experimental transmission of human spongiform encephalopathy. AB - Based on the analysis of genomic DNA from single healthy animals of each of five primate species, nucleotide and predicted amino acid sequences of the infectious amyloid precursor gene of higher apes (Gorilla and Pan) and Old World (Macaca) and New World (Ateles, Saimiri) monkeys showed 95-99% homology to the human sequences, corresponding to their phylogenetic distance from humans. Two of 18 amino acids that differed from humans resulted from nucleotide changes at sites of mutations in humans with familial forms of spongiform encephalopathy (a deleted codon within the codon 51-91 region of 24 bp repeats and a substitution at codon 198). In each of the five animals, codon 129 specified methionine, the more common of the two polymorphic genotypes in humans. Because genotypic homology did not correlate with experimental transmission rates of human spongiform encephalopathy, primary structural similarity of the infectious amyloid precursor protein in humans and experimental primates may not be an important factor in disease transmissibility. PMID- 7991601 TI - Analysis of patterns of DNA sequence variation in flanking and coding regions of murine germ-line immunoglobulin heavy-chain variable genes: evolutionary implications. AB - We analyzed the DNA sequence structure of the 5' flanking and coding regions of 52 VH186.2-related germ-line genes isolated by PCR from C57BL/6J and BALB/c mice. The aligned coding regions display hypervariable and conserved regions corresponding to some of the complementarity-determining regions (CDRs) and framework regions (FRs) found in somatically mutated rearranged immunoglobulin variable genes. Most of the coding regions (88.5%) display open reading frames, strongly suggesting positive selection by antigen. Phylogenetic comparisons of putative transcribed regions versus 5' nontranscribed regions show that they have evolved very differently. Inspection of the 52 murine VH186.2-related DNA sequences (as well as other vertebrate germ-line V sequences reported in the literature) reveals clusters of insertion and deletion events bracketing the transcription/coding unit. These data strongly suggest hyperrecombination events targeting the putative transcription/coding sequence. Given that the DNA of unrearranged germ-line V elements cannot be the direct target for "natural selection" antigen-binding forces (since V elements are only expressed somatically when rearranged in a mature lymphocyte), it is difficult to explain how these nonrandom sequence variations appear in the germ-line DNA. A number of molecular genetic processes are considered, including antigen-driven soma-to-germ line gene feedback operative during vertebrate germ-line V gene evolution. PMID- 7991602 TI - Heparin-dependent binding and autophosphorylation of epidermal growth factor (EGF) receptor by heparin-binding EGF-like growth factor but not by EGF. AB - Heparin-binding EGF-like growth factor (HB-EGF) is a recently identified member of the EGF family of growth factors and a potent mitogen for smooth muscle cells and fibroblasts. Chinese hamster ovary (CHO) cells genetically engineered to express the human EGF receptor bind with high affinity both EGF and HB-EGF. CHO mutant cells lacking heparan sulfate proteoglycans (HSPG) bind EGF equally well to wild-type cells and EGF binding is not affected by exogenous heparin. However, HSPG-deficient EGF receptor-expressing cells do not bind significant levels of HB EGF unless heparin is present in the binding medium. Moreover, binding of radiolabeled EGF to HSPG-deficient EGF receptor-expressing cells is efficiently displaced by nonlabeled HB-EGF only in the presence of heparin. Signal transduction by the EGF receptor tyrosine kinase as evidenced by receptor autophosphorylation is induced by HB-EGF only in the presence of heparin, in contrast to EGF-induced receptor autophosphorylation, which is independent of heparin. These results directly demonstrate that HB-EGF but not EGF requires heparin or cell surface HSPG for binding and activation of the EGF receptor and that HB-EGF receptor interactions can be tightly regulated by the available local concentration of heparin-like molecules. PMID- 7991603 TI - Specific photocrosslinking of DNA-protein complexes: identification of contacts between integration host factor and its target DNA. AB - Azide moieties have been specifically placed in the backbone of DNA by chemical coupling between azidophenacyl bromide and uniquely positioned phosphorothioate residues. The derivatized DNA forms specific complexes with a DNA-binding protein and, following irradiation with 302-nm light, makes specific crosslinks to the protein. Isolation of this covalent complex, followed by tryptic digestion and Edman degradation of the resulting crosslinked peptide, identifies the portion of the protein that is near the derivatized segment of the target DNA. We use this method to probe the interaction between a specific DNA sequence and integration host factor (IHF) protein. A single IHF heterodimer is known to contact > 25 bp of DNA and thereby introduce a sharp bend. Two segments of a typical IHF site were derivatized with aryl azide. Although the segments were separated by only 5 bp, they crosslinked to different subunits of IHF. The locations of the crosslinks support our current view for the way IHF protein binds to and bends its specific targets. PMID- 7991604 TI - In vivo transfer and expression of a human epidermal growth factor gene accelerates wound repair. AB - This report details the transfer of a human epidermal growth factor (hEGF) expression plasmid to porcine partial-thickness wound keratinocytes by particle mediated DNA transfer (Accell). After gene transfer an external sealed fluid filled wound chamber was used to protect the wound, provide containment of the exogenous DNA and expressed peptide, and permit sampling of the wound fluid. Analysis of wound fluid for hEGF and total protein, an indicator of reformation of the epithelial barrier, showed that wounds bombarded with the hEGF plasmid exhibited a 190-fold increase in EGF concentration and healed 20% (2.1 days) earlier than the controls. EGF concentrations in wound fluid persisted over the entire 10-day monitored period, decreasing from 200 pg/ml to 25 pg/ml over the first 5 days. Polymerase chain reaction results showed that plasmid DNA was present in the wound for at least 30 days. These findings demonstrate the possible utility of in vivo gene transfer to enhance epidermal repair. PMID- 7991605 TI - Oligodeoxynucleotides antisense to mRNA encoding protein kinase A, protein kinase C, and beta-adrenergic receptor kinase reveal distinctive cell-type-specific roles in agonist-induced desensitization. AB - The roles of three protein kinases, cyclic AMP-dependent protein kinase (protein kinase A), protein kinase C, and beta-adrenergic receptor kinase (beta ARK), implicated in agonist-induced desensitization of guanine nucleotide-binding protein (G-protein)-coupled receptors were explored in four different cell lines after 48 hr of incubation with oligodeoxynucleotides antisense to the mRNA encoding each kinase. Desensitization of beta 2-adrenergic receptors was analyzed in cell types in which the activities of the endogenous complement of protein kinases A and C and beta ARK were distinctly different. Protein kinase A was necessary for desensitization of rat osteosarcoma cells (ROS 17/2.8), whereas the contribution of beta ARK to desensitization was insignificant. In Chinese hamster ovary cells that stably express beta 2-adrenergic receptors and in smooth muscle cells (DDT1MF-2), oligodeoxynucleotides antisense to beta ARK mRNA nearly abolished desensitization, whereas oligodeoxynucleotides antisense to protein kinase A mRNA attenuated desensitization to a lesser extent. In human epidermoid carcinoma cells (A-431), oligodeoxynucleotides antisense to either protein kinase A mRNA or beta ARK mRNA attenuated agonist-induced desensitization, providing a third scenario in which two kinases constitute the basis for agonist-induced desensitization. In sharp contrast, oligodeoxynucleotides antisense to protein kinase C mRNA were found to enhance rather than attenuate desensitization in DDT1MF-2 and A-431 cell lines, demonstrating counterregulation between prominent protein kinases in desensitization. Using antisense oligodeoxynucleotides to "knock out" target protein kinases in vivo, we reveal distinctive cell-type specific roles of protein kinase A, protein kinase C, and beta ARK in agonist induced desensitization. PMID- 7991606 TI - Terminal protein-primed DNA amplification. AB - By using appropriate amounts of four bacteriophage phi 29 DNA replication proteins--terminal protein, DNA polymerase, protein p6 (double-stranded DNA binding protein), and protein p5 (single-stranded DNA-binding protein)--it has been possible to amplify limited amounts of the 19,285-bp-long phi 29 DNA molecule by three orders of magnitude after 1 hr of incubation at 30 degrees C. Moreover, the quality of the amplified material was demonstrated by transfection experiments, in which infectivity of the synthetic (amplified) phi 29 DNA, measured as the ability to produce phage particles, was identical to that of the natural phi 29 DNA obtained from virions. The results presented in this paper establish some of the requisites for the development of isothermal DNA amplification strategies based on the bacteriophage phi 29 DNA replication machinery that are suitable for the amplification of very large (> 70 kb) segments of DNA. PMID- 7991607 TI - Pancreatic beta cells express a diverse set of homeobox genes. AB - Homeobox genes, which are found in all eukaryotic organisms, encode transcriptional regulators involved in cell-type differentiation and development. Several homeobox genes encoding homeodomain proteins that bind and activate the insulin gene promoter have been described. In an attempt to identify additional beta-cell homeodomain proteins, we designed primers based on the sequences of beta-cell homeobox genes cdx3 and lmx1 and the Drosophila homeodomain protein Antennapedia and used these primers to amplify inserts by PCR from an insulinoma cDNA library. The resulting amplification products include sequences encoding 10 distinct homeodomain proteins; 3 of these proteins have not been described previously. In addition, an insert was obtained encoding a splice variant of engrailed-2, a homeodomain protein previously identified in the central nervous system. Northern analysis revealed a distinct pattern of expression for each homeobox gene. Interestingly, the PCR-derived clones do not represent a complete sampling of the beta-cell library because no inserts encoding cdx3 or lmx1 protein were obtained. Beta cells probably express additional homeobox genes. The abundance and diversity of homeodomain proteins found in beta cells illustrate the remarkable complexity and redundancy of the machinery controlling beta-cell development and differentiation. PMID- 7991608 TI - Substrate spectrum of human excinuclease: repair of abasic sites, methylated bases, mismatches, and bulky adducts. AB - Nucleotide-excision repair is the repair system for removing bulky lesions from DNA. Humans deficient in this repair pathway suffer from xeroderma pigmentosum (XP), a disease characterized by photodermatoses, including skin cancers. At the cellular level, XP patients fail to remove cyclobutane pyrimidine dimers and pyrimidine(6-4)pyrimidone photoproducts induced by UV light, as well as other bulky DNA lesions caused by various genotoxic agents. XP cells are not particularly sensitive to ionizing radiation or to alkylating agents that cause mostly nonbulky DNA lesions. Therefore, it has generally been assumed that the human nucleotide-excision repair enzyme (excinuclease) is specific for bulky adducts. To determine the substrate range of human excinuclease we used the highly sensitive excision assay and tested bulky adducts, synthetic apurinic/apyrimidinic sites, N6-methyladenine, O6-methylguanine, and mismatches as potential substrates. We found that all of these "lesions" were removed by human excinuclease, although with vastly different efficiencies. PMID- 7991609 TI - A molecular chaperone, ClpA, functions like DnaK and DnaJ. AB - The two major molecular chaperone families that mediate ATP-dependent protein folding and refolding are the heat shock proteins Hsp60s (GroEL) and Hsp70s (DnaK). Clp proteins, like chaperones, are highly conserved, present in all organisms, and contain ATP and polypeptide binding sites. We discovered that ClpA, the ATPase component of the ATP-dependent ClpAP protease, is a molecular chaperone. ClpA performs the ATP-dependent chaperone function of DnaK and DnaJ in the in vitro activation of the plasmid P1 RepA replication initiator protein. RepA is activated by the conversion of dimers to monomers. We show that ClpA targets RepA for degradation by ClpP, demonstrating a direct link between the protein unfolding function of chaperones and proteolysis. In another chaperone assay, ClpA protects luciferase from irreversible heat inactivation but is unable to reactivate luciferase. PMID- 7991610 TI - Pulsed growth of fungal hyphal tips. AB - Somatic fungal hyphae are generally assumed to elongate at steady linear rates when grown under constant environmental conditions with ample nutrients. However, patterns of pulsed hyphal elongation were detected during apparent steady growth of hyphal tips in fungi from several major taxonomic groups (Oomycetes, Pythium aphanidermatum and Saprolegnia ferax; Zygomycetes, Gilbertella persicaria; Deuteromycetes, Trichoderma viride; Ascomycetes, Neurospora crassa and Fusarium culmorum; Basidiomycetes, Rhizoctonia solani). Growing hyphal tips were recorded with video-enhanced phase-contrast microscopy at high magnification, and digital images were measured at very short time intervals (1-5 s). In all fungi tested, the hyphal elongation rate was never perfectly steady but fluctuated continuously with alternating periods of fast and slow growth at more or less regular intervals. Pulsed growth was observed in fungi differing in cell diameter, overall growth rate, taxonomic position, and presence and pattern of Spitzenkorper organization, suggesting that this is a general phenomenon. Frequency and amplitude of the pulses varied among the test organisms. T. viride and N. crassa showed the most frequent pulses (average of 13-14 per min), and F. culmorum the least frequent (2.7 per min). Average pulse amplitude varied from 0.012 microns/s for F. culmorum to 0.068 microns/s for G. persicaria. In F. culmorum and T. viride, the fast phase of the growth pulses was correlated with the merger of satellite Spitzenkorper with the main Spitzenkorper. These findings are consistent with a causal relationship between fluctuations in the overall rate of secretory vesicle delivery/discharge at the hyphal apex and the fluctuations in hyphal elongation rate. PMID- 7991611 TI - Tobacco smoke tumor promoters, catechol and hydroquinone, induce oxidative regulation of protein kinase C and influence invasion and metastasis of lung carcinoma cells. AB - Cigarette smoke polyphenolic agents (catechol and hydroquinone) that generate oxidants have been shown to be tumor promoters. Furthermore, oxidants can influence protein kinase C (PKC)-mediated signal transduction. Since terpenoid tumor promoters, phorbol esters, increase invasion and metastasis by activating PKC, we have determined whether polyphenolic agents present in the cigarette smoke condensate (CSC) could also influence these events. Hydroquinone (50 microM), catechol (500 microM), or CSC (50 micrograms/ml) induced an initial cytosol-to-membrane translocation of PKC in LL/2 lung carcinoma cells, followed by a later down-regulation of the enzyme. LL/2 cells treated with these CSC related agents for a limited time (45 min) and exhibiting high membrane associated PKC activity, when injected into mice through the tail vein, produced an increase in metastatic nodules in the lungs after 20 days. However, cells treated with CSC-related agents for a prolonged period did not exhibit an increase in metastasis. Agents that decrease the rate of production of reactive oxygen species, such as catalase either alone or in combination with superoxide dismutase, and a cell-permeable iron-chelator, o-phenanthroline, inhibited CSC mediated membrane association of PKC and metastasis. Prior treatment of CSC with tyrosinase to modify polyphenols resulted in a partial loss of CSC stimulation of metastasis. Furthermore, a cell-permeable Ca2+ chelator and diverse PKC inhibitors, such as calphostin C, hypericin, chelerythrine, and bisindolylmaleimide, inhibited CSC-enhanced metastasis. CSC increased in vitro tumor cell adhesion to endothelial monolayers and to reconstituted basement membrane (Matrigel) and also enhanced the invasion through Matrigel coated on the polycarbonate filters in Transwells. All these CSC effects were found to be temporary and were blocked by the above mentioned antioxidant systems and PKC inhibitors. Thus, these results suggest that the oxidants generated by autooxidation of polyphenolic agents present in tobacco smoke increase tumor cell invasion and metastasis, at least in part by activation of Ca2+/PKC signal transduction. Conceivably, cigarette smoke constituents not only promote tumorigenesis but also may increase the spread of cancer in the body. PMID- 7991612 TI - Critical role of the group A streptococcal capsule in pharyngeal colonization and infection in mice. AB - To study the role of the group A streptococcal capsule in pharyngeal colonization, we used two acapsular mutants derived from a type 24 strain of group A Streptococcus by transposon mutagenesis. One mutant had a stable acapsular phenotype due to a transposon-associated chromosomal deletion of essential capsule synthetic genes, while the second mutant could revert to the encapsulated phenotype at a low frequency (< 10(-4)) upon spontaneous excision of the transposon from the capsule-synthesis region of the chromosome. Both acapsular mutants were sensitive to phagocytic killing in vitro and had reduced virulence in mice after intraperitoneal challenge. Mice inoculated intranasally with the stable acapsular mutant rapidly cleared the organisms from the pharynx, and no mice died. In contrast, throat cultures of animals challenged with the revertible mutant yielded many encapsulated revertants, and mortality was similar to that of animals challenged with the parent strain. The rapid emergence of a population of encapsulated revertants in the pharynx implies that the capsule conferred a powerful selective advantage in this environmental niche. Together with the complete avirulence of the stable acapsular mutant, these observations indicate that the hyaluronic acid capsule plays a critical role in colonization and infection of the pharynx by group A streptococci. PMID- 7991613 TI - Beta-amyloid neurotoxicity requires fibril formation and is inhibited by congo red. AB - beta-Amyloid (beta A) is normally produced as a nontoxic soluble peptide. In Alzheimer disease, beta A aggregates and accumulates in the brain as inert diffuse plaques or compact plaques associated with neurodegenerative changes. To determine the relationship of neurotoxicity to the physical state of beta A, we created (i) nonamyloidogenic amorphous aggregates of beta A [amorphous beta A (Am beta A)] analogous to diffuse plaques and (ii) amyloidogenic fibrils of beta A [fibrillar beta A (Fib-beta A)] analogous to compact plaques. In primary rat hippocampal culture, Fib-beta A was neurotoxic, whereas Am-beta A was not toxic. Fib-beta A caused significant loss of synapses in viable neurons, while Am-beta A had no effect on synapse number. The amyloid fibril-binding dye Congo red inhibited Fib-beta A neurotoxicity by inhibiting fibril formation or by binding to preformed fibrils. Congo red also inhibited the pancreatic islet cell toxicity of diabetes-associated amylin, another type of amyloid fibril. These results indicate that beta A neurotoxicity requires fibril formation. These findings and our previous demonstration that amylin fibrils are toxic suggest that a common cytopathic effect of amyloid fibrils may contribute to the pathogenesis of Alzheimer disease and other amyloidoses. PMID- 7991615 TI - Isolation of a DEAD-family protein gene that encodes a murine homolog of Drosophila vasa and its specific expression in germ cell lineage. AB - In an effort to study the molecular basis of the determination processes of the mammalian germ cell lineage, we have tried to isolate a mouse gene homolog to vasa, which plays an essential role as a maternal determining factor for the formation of Drosophila germ cell precursors. By reverse transcriptase PCRs of mouse primordial germ cell cDNAs using family-specific primers, we obtained a gene (Mvh) encoding a DEAD-family protein that showed a much higher degree of similarity with the product of the Drosophila vasa gene (vas) than previously reported mouse genes. In adult tissues, Mvh transcripts were exclusively detected in testicular germ cells, in which Mvh protein was found to be localized in cytoplasm of spermatocytes and round spermatids including a perinuclear granule. The protein was also expressed in germ cells colonized in embryonic gonads but was not detected in pluripotential embryonic cells such as stem cells and germ cells. These results suggest the possibility that the Mvh protein may play an important role in the determination events of mouse germ cells as in the case of Drosophila vasa. PMID- 7991614 TI - Aconitase is a sensitive and critical target of oxygen poisoning in cultured mammalian cells and in rat lungs. AB - The effect of hyperoxia on activity of the superoxide-sensitive citric acid cycle enzyme aconitase was measured in cultured human epithelial-like A549 cells and in rat lungs. Rapid and progressive loss of > 80% of the aconitase activity in A549 cells was seen during a 24-hr exposure to a PO2 of 600 mmHg (1 mmHg = 133 Pa). Inhibition of mitochondrial respiratory capacity correlated with loss of aconitase activity in A549 cells exposed to hyperoxia, and this effect could be mimicked by fluoroacetate (or fluorocitrate), a metabolic poison of aconitase. Exposure of rats to an atmospheric PO2 of 760 mmHg or 635 mmHg for 24 hr caused respective 73% and 61% decreases in total lung aconitase activity. We propose that early inactivation of aconitase and inhibition of the energy-producing and biosynthetic reactions of the citric acid cycle contribute to the sequelae of lung damage and edema seen during exposure to hyperoxia. PMID- 7991616 TI - An anti-peptide antibody specific for the class A calcium channel alpha 1 subunit labels mammalian neuromuscular junction. AB - We have generated an anti-peptide antibody specific for the class A calcium channel alpha 1 subunit from rat brain. In immunoblots of the calcium channel complex partially purified from rat brain membranes, the antibody specifically recognized two doublets, one of apparent M(r) 210,000 and M(r) 180,000 and another of apparent M(r) 160,000 and M(r) 130,000. Immunofluorescent staining of sections of rat diaphragm showed that this antibody specifically recognizes antigens that are highly concentrated at neuromuscular synapses. Using this antibody, we also examined the distribution of the class A alpha 1 subunit in sagittal sections of rat cerebellum by immunoperoxidase staining. Specific immunoreactivity was localized in the granule cell layer, possibly to the cerebellar glomeruli, the unique structures in cerebellum where mossy fibers synapse with granule cell dendrites. Purkinje cell neurons were not stained specifically. These results indicate that the class A calcium channel alpha 1 subunit is highly concentrated at mammalian neuromuscular junction and has a restricted localization in cerebellum that does not include Purkinje cell soma or dendrites. PMID- 7991617 TI - Motility voltage sensor of the outer hair cell resides within the lateral plasma membrane. AB - The outer hair cell (OHC) from the organ of Corti is believed to be responsible for the mammal's exquisite sense of hearing. A membrane-based motile response of this cell underlies the initial processing of acoustic energy. The voltage dependent capacitance of the OHC, possibly reflecting charge movement of the motility voltage sensor, was measured in cells during intracellular dialysis of trypsin under whole cell voltage clamp. Within 10 min after dialysis, light and electron microscopic examination revealed that the subplasmalemmal structures, including the cytoskeletal framework and subsurface cisternae, were disrupted and/or detached from adjacent plasma membrane. Dialysis of heat-inactivated trypsin produced no changes in cell structure. Simultaneous measures of linear and nonlinear membrane capacitance revealed minimal changes, indicating that contributions by subsurface structures to the generation of the nonlinear capacitance are unlikely. This study strongly suggests that voltage-dependent charge movement in the OHC reflects properties of the force generator's voltage sensor and that the sensor/motor resides solely within the lateral plasma membrane. PMID- 7991618 TI - Chemiluminescent activation of the antiviral activity of hypericin: a molecular flashlight. AB - Hypericin is a naturally occurring photosensitizer that displays potent antiviral activity in the presence of light. The absence of light in many regions of the body may preclude the use of hypericin and other photosensitizers as therapeutic compounds for the treatment of viral infections in vivo. The chemiluminescent oxidation of luciferin by the luciferase from the North American firefly Photinus pyralis was found to generate sufficiently intense and long-lived emission to induce antiviral activity of hypericin. Light-induced virucidal activity of hypericin was demonstrated against equine infectious anemia virus, a lentivirus structurally, genetically, and antigenically related to the human immunodeficiency virus. The implications for exploiting chemiluminescence as a "molecular flashlight" for effecting photodynamic therapy against virus-infected cells and tumor cells are discussed. PMID- 7991619 TI - Dollo's law and the death and resurrection of genes. AB - Dollo's law, the concept that evolution is not substantively reversible, implies that the degradation of genetic information is sufficiently fast that genes or developmental pathways released from selective pressure will rapidly become nonfunctional. Using empirical data to assess the rate of loss of coding information in genes for proteins with varying degrees of tolerance to mutational change, we show that, in fact, there is a significant probability over evolutionary time scales of 0.5-6 million years for successful reactivation of silenced genes or "lost" developmental programs. Conversely, the reactivation of long (> 10 million years)-unexpressed genes and dormant developmental pathways is not possible unless function is maintained by other selective constraints; the classic example of the resurrection of "hen's teeth" is most likely an experimental artifact, and the experimental reactivation of the Archaeopteryx limb developmental program has been shown to be a misinterpretation. For groups undergoing adaptive radiations, lost features may "flicker" on and off, resulting in a distribution of character states that does not reflect the phylogeny of the group. PMID- 7991621 TI - Bootstrap hypothesis tests for evolutionary trees and other dendrograms. AB - The bootstrap computer-intensive statistical technique is frequently applied to statistical analyses of phylogenetic trees. The widely used rule that a group is supported significantly if it appears in at least 95% of bootstrap trees is conservative in most situations. This paper describes three ways of using the bootstrap to carry out statistical inference on phylogenies. The first method tests whether there is nonrandom support for a single group or tree. The second method compares the support for two groups or trees. The third method tests whether a single group or tree has better support than the set of all possible alternatives; this may be a replacement for the "95% rule." These tests generally require fewer bootstrap trees to be estimated than do other methods of bootstrapping phylogenies. A simple, sequential statistical method can be used to increase the efficiency further. These methods can be applied to tests of multiple hypotheses about a single phylogeny. Parsimony analyses of 5S rRNA sequences of plants and cluster analyses of randomly amplified polymorphic DNA bands in three pathotypes of the cereal eyespot fungus are used as illustrative examples. The tests can be used to analyze dendrograms in subjects other than taxonomy. PMID- 7991620 TI - African origin of human-specific polymorphic Alu insertions. AB - Alu elements are a family of interspersed repeats that have mobilized throughout primate genomes by retroposition from a few "master" genes. Among the 500,000 Alu elements in the human genome are members of the human-specific subfamily that are not fixed in the human species; that is, not all chromosomes carry an Alu element at a particular locus. Four such polymorphic human-specific Alu insertions were analyzed by a rapid, PCR-based assay that uses primers that flank the insertion point to determine genotypes based on the presence or absence of the Alu element. These four polymorphic Alu insertions were shown to be absent from the genomes of a number of nonhuman primates, consistent with their arising as human genetic polymorphisms sometime after the human/African ape divergence. Analysis of 664 unrelated individuals from 16 population groups from around the world revealed substantial levels of variation within population groups and significant genetic differentiation among groups. No significant associations were found among the four loci, consistent with their location on different chromosomes. A maximum likelihood tree of population relationships showed four major groupings consisting of Africa, Europe, Asia/Americas, and Australia/New Guinea, which is concordant with similar trees based on other loci. A particularly useful feature of the polymorphic Alu insertions is that the ancestral state is known to be the absence of the Alu element, and the presence of the Alu element at a particular chromosomal site reflects a single, unique event in human evolution. A hypothetical ancestral group can then be included in the tree analysis, with the frequency of each insertion set to zero. The ancestral group connected to the maximum-likelihood tree within the African branch, which suggests an African origin of these polymorphic Alu insertions. These data are concordant with other diverse data sets, which lends further support to the recent African origin hypothesis for modern humans. Polymorphic Alu insertions represent a source of genetic variation for studying human population structure and evolution. PMID- 7991622 TI - Synthesis and biological activities of highly potent antagonists of growth hormone-releasing hormone. AB - In the search for antagonists of human growth hormone-releasing hormone (hGHRH) with high activity, 22 analogs were synthesized by solid-phase methods, purified, and tested biologically. Within the N-terminal sequence of 28 or 29 amino acids of hGHRH, all the analogs contained D-Arg2, Phe(4-Cl)6 (para chlorophenylalanine), Abu15 (alpha-aminobutyric acid), and Nle27 and most of them had Agm29 (agmatine) substituents. All the peptides, except one, were acylated at the N terminus with different hydrophobic acids--e.g., isobutyric acid (Ibu) or 1 naphthylacetic acid (Nac) in order to study the effect of N-terminal acylation on the antagonistic activity. In the superfused rat pituitary cell system, all the analogs inhibited more powerfully the GHRH-induced growth hormone (GH) release than the standard GHRH antagonist [Ac-Tyr1,D-Arg2]hGHRH-(1-29)NH2. Antagonists [Ibu0,D-Arg2,Phe(4-Cl)6,Abu15,Nle27]hGHRH-(1-28) Agm (MZ-4-71), [Nac0,D Arg2,Phe(4-Cl)6,Abu15,Nle27]hGHRH-(1-28) Agm (MZ-4-243), [Nac0,D-Arg2,Phe(4 Cl)6,Abu15,Nle27]hGHRH-(1-29) NH2 (MZ-4-169), [Nac0-His1,D-Arg2,Phe(4 Cl)6,Abu15,Nle27]-hGH RH-(1-29)NH2 (MZ-4-181), and [Nac0,D-Arg2,Phe(4 Cl)6,Abu15,Nle27,Asp28]hGH RH-(1-28)Agm (MZ-4-209) inhibited GH release at 3 x 10(-9) M. Among these peptides, MZ-4-243, MZ-4-169, and MZ-4-181 were also long acting in vitro. Antagonist MZ-4-243 inhibited GH release 100 times more powerfully than the standard antagonist and was the most potent in vitro among GHRH antagonists synthesized. Analogs with high inhibitory effects in vitro were also found to have high affinities to rat pituitary GHRH receptors. In experiments in vivo, antagonists [Ibu0,D-Arg2,Phe(4-Cl)6,Abu15,Nle27]-hGHRH-(1-28 )Agm (MZ-4-71), [Nac0,D-Arg2,Phe(4-Cl)6,Abu15,Nle27]hGHRH-(1-29) NH2 (MZ-4-169), and [Nac0-His1,D-Arg2,Phe(4-Cl)6,Abu15,Nle27]hGHR H-(1-29)NH2 (MZ-4-181) induced a significantly greater inhibition of GH release than the standard antagonist. In view of their high antagonistic activity and prolonged duration of action, some of these antagonists of GHRH may find clinical applications, including treatment of certain endocrine disorders and insulin-like growth factor I-dependent tumors. PMID- 7991623 TI - Key role for pregnenolone in combination therapy that promotes recovery after spinal cord injury. AB - Controlled compressive injury to rat spinal cord was chosen to test therapies that might attenuate the progression of tissue destruction and locomotor deficits that characteristically occur after spinal injury. A highly significant reduction of damage was achieved by immediate postinjury treatment with a combination of the following: an antiinflammatory substance, indomethacin; a stimulator of cytokine secretion, bacterial lipopolysaccharide; and the parent steroid, from which all other steroids arise, pregnenolone. This treatment reduced histopathological changes, spared tissue from secondary injury, and increased restoration of motor function. Remarkably, 11 of 16 of the animals treated with the above combination were able to stand and walk at 21 days after injury, 4 of them almost normally. The results were far superior to those obtained in controls or in animals to which the substances were given separately or in combination of two. This approach may prove to be applicable to nervous system injury, in general, and to injury in other tissues. PMID- 7991624 TI - "Metabolic switch" for desert survival. AB - Food, like water, is in short supply in the desert. We report a specialized mechanism used by a desert mouse for surviving prolonged food shortages. The key element of this adaptation is a large reduction in resting metabolism. After about 2 weeks of restricted food intake (50% of normal), the desert mouse "switched down" its resting metabolism and was able to survive and maintain its weight indefinitely on these limited rations. When food was again freely available, resting metabolism "switched up," returning to normal levels in a single day. The reduced metabolism occurred without a decrease in body temperature or in levels of activity. In marked contrast, metabolism of the laboratory white mouse increased during food restriction, and the experiments had to be terminated to avoid starvation. We think this "metabolic switch" is common among desert mammals. It may be an amplification of a general metabolic response for coping with food scarcity common to all mammals, including humans. PMID- 7991625 TI - Modulator factor-binding sequence of the sea urchin early histone H2A promoter acts as an enhancer element. AB - The sea urchin early H2A histone gene, like the other four members of the repeating units, is transiently expressed during very early development. To investigate the mechanisms underlying the faithful expression of the early H2A gene, we focused our attention on the modulator element. We showed by DNase I cleavage protection patterns that the modulator includes the upstream sequence element 1 (USE1) and mapped at nucleotides -137 to -108 in the early H2A gene promoter. Functional tests conducted by microinjection into sea urchin embryos then showed that the modulator element binds the transcriptional factor called modulator-binding factor 1 (MBF-1). We found in fact that coinjection of an excess of the MBF-1-binding site, either as the modulator or as the USE1, efficiently impaired the activity of the H2A promoter. An unexpected finding was the expression of the reporter gene from the early H2A promoter at the gastrula stage of embryonic development, when the early histone genes are transcriptionally silent. In addition, we also found that the modulator element was active at the gastrula stage. The potential enhancer activity of the modulator was tested by microinjecting several constructs containing single or multiple copies of the modulator element placed 5' or 3' to a thymidine kinase gene (tk) promoter in both sea urchin embryos and Xenopus laevis oocytes and determining the expression of a reporter chloramphenicol acetyltransferase gene under the control of the linked tk promoter. We found that an oligonucleotide bearing the MBF-1-binding site activates the expression of the reporter gene independently of the position and orientation. We conclude that the modulator binds the MBF-1 activator and that it is a transcriptional enhancer of the early H2A histone gene. PMID- 7991626 TI - A functional chimeric DNA primase: the Cys4 zinc-binding domain of bacteriophage T3 primase fused to the helicase of bacteriophage T7. AB - Two colinear bacteriophage T7 gene 4 proteins provide helicase and primase functions in vivo. T7 primase differs from T7 helicase by an additional 63 residues at the amino terminus. This terminal domain contains a zinc-binding motif which mediates an interaction with the basic primase recognition sequence 3'-CTG-5'. We have generated a chimeric primase in which the 81 amino-terminal residues are derived from the primase of phage T3 and the 484 carboxyl-terminal residues are those of phage T7 helicase. The amino-terminal domain of T3 primase is 50% homologous with that of T7 primase. The resulting T3/T7 chimeric protein is a functional primase in vivo. While the primase activity of the purified protein is about one-third that of T7 primase, the recognition sites used and the oligoribonucleotides synthesized from these sites are identical. We conclude that the residues responsible for the interaction with the sequence 3'-CTG-5' are conserved between the chimeric and T7 proteins. PMID- 7991627 TI - DNA oxidative damage and life expectancy in houseflies. AB - The objective of this study was to explore the relationship between oxidative molecular damage and the aging process by determining whether such damage is associated with the rate of aging, using the adult housefly as the experimental organism. Because the somatic tissues in the housefly consist of long-lived postmitotic cells, it provides an excellent model system for studying cumulative age-related cellular alterations. Rate of aging in the housefly was manipulated by varying the rate of metabolism (physical activity). The concentration of 8 hydroxydeoxyguanosine (80HdG) was used as an indicator of DNA oxidation. Exposure of live flies to x-rays and hyperoxia elevated the level of 8OHdG. The level of 8OHdG in mitochondrial as well as total DNA increased with the age of flies. Mitochondrial DNA was 3 times more susceptible to age-related oxidative damage than nuclear DNA. A decrease in the level of physical activity of the flies was found to prolong the life-span and corresponding reduce the level of 8OHdG in both mitochondrial and total DNA. Under all conditions examined, mitochondrial DNA exhibited a higher level of oxidative damage than total DNA. The 8OHdG levels were found to be inversely associated with the life expectancy of houseflies. The pattern of age-associated accrural of 8OHdG was virtually identical to that of protein carbonyl content. Altoghether, results of this study support the hypothesis that oxidative molecular damage is a causal factor in senescence. PMID- 7991628 TI - Tracking the origins of the cave bear (Ursus spelaeus) by mitochondrial DNA sequencing. AB - The different European populations of Ursus arctos, the brown bear, were recently studied for mitochondrial DNA polymorphism. Two clearly distinct lineages (eastern and western) were found, which may have diverged approximately 850,000 years ago. In this context, it was interesting to study the cave bear, Ursus spelaeus, a species which became extinct 20,000 years ago. In this study, we have amplified and sequenced a fragment of 139-bp in the mitochondrial DNA control region of a 40,000-year-old specimen of U. spelaeus. Phylogenetic reconstructions using this sequence and the European brown bear sequences already published suggest that U. spelaeus diverged from an early offshoot of U. arctos--i.e., approximately at the same time as the divergence of the two main lineages of U. arctos. This divergence probably took place at the earliest glaciation, likely due to geographic separation during the earlier Quaternary cold periods. This result is in agreement with the paleontological data available and suggests a good correspondence between molecular and morphological data. PMID- 7991629 TI - Neurotrophin 3 potentiates neuronal activity and inhibits gamma-aminobutyratergic synaptic transmission in cortical neurons. AB - Neurotrophins have traditionally been regarded as slowly acting signals essential for neuronal survival and differentiation. However, brain-derived neurotrophic factor and neurotrophin 3 (NT-3) have recently been reported to exert an acute potentiation of synaptic activity at the amphibian neuromuscular junction. Little is known about the role of neurotrophins on functional synapses in the central nervous system. Here we show that NT-3 rapidly increased the frequency of spontaneous action potentials, and it synchronized excitatory synaptic activities in developing cortical neurons. Moreover, the inhibitory synaptic transmission mediated by gamma-aminobutyric acid (GABA) subtype A receptors was found to be reduced by NT-3. Thus, the excitatory effects of NT-3 on spontaneous action potentials were attributable to a reduction of GABAergic transmission. Our findings, together with previous reports of rapid regulation of central nervous system neurotrophin expression by neuronal activity and of the role of GABAergic transmission in cortical plasticity, suggest a mechanism for modulation of synaptic transmission and activity-dependent synaptic modulation in cortical neurons. PMID- 7991630 TI - A mutation in segment IVS6 disrupts fast inactivation of sodium channels. AB - Na(+)-channel inactivation is proposed to occur by binding of an intracellular inactivation gate to a hydrophobic inactivation gate receptor in the intracellular mouth of the pore. Amino acid residues in transmembrane segment S6 of domain IV (IVS6) that are critical for fast inactivation were identified by alanine-scanning mutagenesis. Mutant VIL1774-6AAA, in which three adjacent residues (Val-Ile-Leu) at the intracellular end of segment IVS6 were converted to alanine, had substantial (> 85%) sustained Na+ currents remaining 15 ms after depolarization, while a nearby mutation of three residues to alanine had no effect. Single-channel analysis revealed continued reopenings late in 40-ms depolarizing pulses indicating that inactivation was substantially impaired compared to wild type. The mean open time for VIL1774-6AAA was longer than wild type, suggesting that this mutation also decreases the rate of entry into the fast inactivated state. These results suggest that residues near the intracellular end of segment IVS6 are critical for fast Na(+)-channel inactivation and may form part of the hydrophobic receptor site for the fast inactivation gate. PMID- 7991633 TI - The cortical Enigma: a reply to Professor Gregory. AB - The phenomenon of motion from form, as seen in the Enigma figure, can be used for studying brain-induced processes of 'illusory' motion perception. PMID- 7991632 TI - Inhibitory K+ current activated by odorants in toad olfactory neurons. AB - Odorant responses of isolated olfactory neurons from the toad Caudiverbera caudiverbera were monitored by using patch-clamp techniques. Depending on the stimulus, the same neuron responded with an increase or a decrease in action potential firing. Odorants that activate the cAMP cascade in olfactory cilia increased electrical activity, caused membrane depolarization, and triggered inward currents. In contrast, odorants that do not activate the cAMP cascade inhibited electrical activity, produced membrane hyperpolarization, and activated outward currents in a dose-dependent fashion. Such currents were carried by K+ and blocked by tetraethylammonium. Similar currents were recorded from Xenopus laevis. Our results suggest that this K+ current is responsible for odorant induced inhibition of action potential firing in olfactory neurons. PMID- 7991634 TI - Life-history trade-offs and the evolution of pathogen resistance: competition between host strains. AB - The dynamics of a 'resistant' and a 'susceptible' strain of a self-regulated host species, in the presence of a directly transmitted pathogen, is investigated. The two strains trade off differences in pathogen transmissibility (as an aspect of pathogen resistance) against differences in birth rate and/or resistance to crowding. Depending on parameter values, either strain may be eliminated, or the two may coexist (along with the pathogen). Coexistence (polymorphism), unsurprisingly, requires an appropriate balance between the different advantages possessed by the two strains. The probability of coexistence through such a balance, however, varies nonlinearly with the degree of difference between the strains: coexistence is least likely between two very similar strains. Resistance is most likely to evolve in hosts with the characteristics of many insect pests. Moreover, with highly pathogenic pathogens, a 'susceptible' strain may exclude a 'resistant' strain because its higher growth rate is more effective against the pathogen than reduced transmissibility. 'Resistance' can reside in parameters other than those directly associated with the pathogen. Although no cycles arise and no chaotic behaviour is found, an oscillatory approach to equilibrium is commonly observed, signalling the possibility of observable oscillations in strain frequency in the (more variable) real world. PMID- 7991631 TI - Modulation of brain Na+ channels by a G-protein-coupled pathway. AB - Na+ channels in acutely dissociated rat hippocampal neurons and in Chinese hamster ovary (CHO) cells transfected with a cDNA encoding the alpha subunit of rat brain type IIA Na+ channel (CNaIIA-1 cells) are modulated by guanine nucleotide binding protein (G protein)-coupled pathways under conditions of whole cell voltage clamp. Activation of G proteins by 0.2-0.5 mM guanosine 5'-[gamma thio]triphosphate (GTP[gamma S]), a nonhydrolyzable GTP analog, increased Na+ currents recorded in both cell types. The increase in current amplitude was caused by an 8- to 10-mV negative shift in the voltage dependence of both activation and inactivation. The effects of G-protein activators were blocked by treatment with pertussis toxin or guanosine 5'-[beta-thio]diphosphate (GDP[beta S]), a nonhydrolyzable GDP analog, but not by cholera toxin. GDP[beta S] (2 mM) alone had effects opposite those of GTP[gamma S], shifting Na(+)-channel gating 8 10 mV toward more-positive membrane potentials and suggesting that basal activation of G proteins in the absence of stimulation is sufficient to modulate Na+ channels. In CNaIIA-1 cells, thrombin, which activates pertussis toxin sensitive G proteins in CHO cells, caused a further negative shift in the voltage dependence of Na(+)-channel activation and inactivation beyond that observed with GTP alone. The results in CNaIIA-1 cells indicate that the alpha subunit of the Na+ channel alone is sufficient to mediate G protein effects on gating. The modulation of Na+ channels via a G-protein-coupled pathway acting on Na(+) channel alpha subunits may regulate electrical excitability through integration of different G-protein-coupled synaptic inputs. PMID- 7991635 TI - The major secreted product of the whipworm, Trichuris, is a pore-forming protein. AB - The data presented here describe the first unequivocable characterization of a pore-forming protein in any helminth parasite. The excretory/secretory (E/S) material of the human whipworm T. trichiura contains a highly abundant protein of molecular mass 47 kDa (TT47); the murine model parasite, T. muris, contains a similarly abundant protein of molecular mass 43 kDa (TM43). When purified to homogeneity, these proteins induce ion-conducting pores in lipid bilayers. Antibodies raised against TM43 abolish channel activity. Pore formation in epithelial cell membranes may facilitate invasion of the host gut by Trichuris and enable the parasite to maintain its syncytial environment in the caecal epithelium. The observation that this activity may be inhibited by antibody opens a possible avenue for drug and vaccine development. PMID- 7991636 TI - Novel synapses compensate for a neuron ablated in embryos. AB - In leeches, as well as mammals, neuronal death in adults produces lasting deficits, whereas the embryonic nervous system is believed to be more plastic. Killing the single S interneuron in an adult leech ganglion permanently interrupts the chain of S cells linked by electrical synapses along the entire animal. Axons that synapsed with the ablated neuron do not change length in response to cell ablation, but they will grow if another axon of the same neuron is injured. In the present experiments, the S cell and surrounding cells in one ganglion were ablated with a fine pin during embryogenesis (day 8-11). Effects were evaluated 1-4 months later. Cell-specific monoclonal antibody confirmed S cell deletions. Intracellular injection of horseradish peroxidase and 6 carboxyfluorescein dye showed that intact S cells' axons projected twice their usual length into the lesioned ganglion and formed electrical synapses with homologues of their usual synaptic targets. Conduction was often restored by these connections, which replaced those of the deleted S cell. Therefore, in both adults and embryos, growing S interneurons respond to loss of a target by greater growth. However, only on the small scale of the embryo is growth sufficient to reach suitable targets. PMID- 7991637 TI - Animal body size distributions change as more species are described. AB - Frequency distributions of body size have been reported in the literature for a range of animal higher taxa. However, the reported shapes of these distributions may be biased by species missing from them, specifically by currently undiscovered species. There is a body of evidence that the small-bodied species in a taxon are described later, on average, than the large-bodied. From this, we predict that the means of animal body size frequency distributions should decrease through time, and the skewnesses of the distributions increase. These predictions are shown to be true for body size distributions for five different higher taxa of animals. Thus, any reported body size distribution for a taxon is likely to be systematically biased, even if it includes all the species which are known, if many species are likely to remain undiscovered. PMID- 7991638 TI - Melanocortins as factors in somatic neuromuscular growth and regrowth. AB - Melanocortins, non-corticotropic fragments of adrenocorticotropic hormone, accelerate growth of the developing neuromuscular system and regrowth of damaged neurons, both in the adult and neonatal rat. Morphological, electrophysiological and behavioral characteristics are all improved by melanocortins, which, however, vary in potency, with alpha-MSH being the most effective. Tissue substrate, dosage, critical time periods and pattern of neuropeptide administration are all important variables. Melanocortins protect central neurons affecting motor behavior during development or following neuronal damage in the adult brain. Possible mechanisms of melanocortin action are discussed. PMID- 7991639 TI - Role of insulin-like growth factors in peripheral nerve regeneration. AB - Prolonged denervation results in atrophy of target organs and increased risk of permanent paralysis. A better understanding of the mechanism responsible for nerve regeneration may one day lead to improved rates of nerve regeneration and diminished risk of loss of function. Neurobiologists have known for decades that soluble neurotrophic activity is present in nerves and nerve targets. Until recently, the soluble molecules that regulate the rate of nerve regeneration have eluded identification. Insulin-like growth factor (IGF) gene expression is correlated with synapse formation during development and regeneration. IGFs are now identified as the first soluble nerve- and muscle-derived neurotrophic factors found to regulate the rate of peripheral nerve regeneration. The roles of IGFs and other neurotrophic factors in peripheral nerve regeneration, motor nerve terminal sprouting and synapse formation are reviewed. PMID- 7991640 TI - Intestinal toxicity of non-steroidal anti-inflammatory drugs. AB - We review the adverse effect of non-steroidal anti-inflammatory drugs (NSAIDs) on the small and large intestine. NSAIDs cause small intestinal inflammation in 65% of patients receiving the drugs long-term. The clinical implications of NSAID induced enteropathy are that patients bleed and lose protein from the inflammatory site, contributing to iron deficiency and hypoalbuminemia, respectively. Some patients develop intestinal strictures, which may require surgery, and the occasional one may develop discrete ulcers with perforations. There are a number of therapeutic options available to treat the enteropathy and the attendant complications, including antibiotics, sulphasalazine and misoprostol. The colon, by comparison, is only rarely affected by NSAIDs, but colitis is well recognized and NSAIDs may be an important factor in diverticular complications and the relapse of inflammatory bowel disease. There is an association between NSAID intake and appendicitis in the elderly. PMID- 7991641 TI - The importance of 5-hydroxytryptamine receptors in the gut. AB - Most of the 5-hydroxytryptamine (5-HT) present in the adult human body is located in the gastrointestinal tract. The vast majority is contained in enteroendocrine cells, the rest exists mainly in myenteric interneurons separated from the mucosa by an intraenteric barrier. Physiological studies suggest that 5-HT plays a vital role in mediating both sensory and reflex responses to gastrointestinal stimuli and, thus, this transmitter is closely implicated in gut reactions. This review outlines some of the evidence for different 5-HT receptors, summarizes the role of 5-HT in mediating gut sensitivity and motor activity, secretion and more complex activities, such as emesis and diarrhoea and identifies the clinical role of drugs acting on 5-HT receptors in the treatment of emesis, diarrhoea, the control of abdominal pain and discomfort and the rectification of gastrointestinal motility. PMID- 7991642 TI - Comparative toxicity of non-steroidal anti-inflammatory agents. AB - Comparative toxicity of non-steroidal anti-inflammatory drugs was assessed using the Stanford Toxicity Index consisting of weighted symptoms, laboratory abnormalities and hospitalizations in 2976 consecutively enrolled rheumatoid arthritis patients from eight data bank centers with 27,936 patient-years of observation. Scores ranged from 1.77 (SE 0.20) for aspirin to 5.94 (SE 0.92) for meclofenamate, with many differences between drugs being 2- to 3-fold and highly statistically significant. Results are consistent with our prior data, persist when assessed by several different scoring algorithms, are consistent across data bank centers and are consistent with data of others. There are major and reproducible differences in the overall toxicity of different non-steroidal anti inflammatory drugs. PMID- 7991643 TI - Breast milk as a source of vitamins, essential minerals and trace elements. AB - Human breast milk provides all of the vitamins and essential minerals and trace elements (micronutrients) that are required by the normal term infant, until weaning. With a few exceptions, excessive micronutrient supplies to the mother, or a moderate deficiency in her diet, do not greatly alter the supply to the infant. Thus, the infant is well-protected by maternal homeostatic processes, although the mechanisms of these are not yet well understood. Considerable progressive changes in concentration occur for some of the micronutrients during the course of lactation. Because the concentration of these nutrients, and of other substances that modify their absorption by the infant, such as binding proteins, differs considerably between human milk, animal milk and, hence, commercial milk formulae, there is great interest in the quantitative significance of micronutrient supplies, and their variability in breast milk, in the quest for improvement of commercial formulations. The aim of this review is to summarize the available information about the factors that determine breast milk contents of micronutrients. PMID- 7991645 TI - Negative regulators of cell proliferation. AB - Cell proliferation is governed by the influence of both mitogens and inhibitors. Although cell contact has long been thought to play a fundamental role in cell cycling regulation, and negative regulators have long been suspected to exist, their isolation and purification has been complicated by a variety of technical difficulties. Nevertheless, over recent years an ever-expanding list of putative negative regulators have emerged. In many cases, their biological inhibitory activities are consistent with density-dependent growth inhibition. Most likely their interactions with mitogenic agents, at an intracellular level, are responsible for either mitotic arrest or continued cell cycling. A review of naturally occurring cell growth inhibitors is presented with an emphasis on those factors shown to be residents of the cell surface membrane. Particular attention is focused on a cell surface sialoglycopeptide, isolated from intact bovine cerebral cortex cells, which has been shown to inhibit the proliferation of an unusually wide range of target cells. The glycopeptide arrest cells obtained from diverse species, both fibroblasts and epithelial cells, and a broad variety of transformed cells. Signal transduction events and a limited spectrum of cells that are refractory to the sialoglycopeptide have provided insight into the molecular events mediated by this cell surface inhibitor. PMID- 7991644 TI - Phosphoinositide metabolism in airway smooth muscle. AB - Agonist-stimulated hydrolysis of phosphatidylinositol 4,5-bisphosphate, which generates inositol 1,4,5-trisphosphate and sn-1,2-diacylglycerol, is thought to be one of the major mechanisms underlying pharmacomechanical coupling in airway smooth muscle. This article is a review of the currently available information on phosphoinositide and inositol 1,4,5-trisphosphate metabolism in this tissue and includes data on inositol 1,4,5-trisphosphate-induced Ca2+ release and the receptor mediating this effect. The final section outlines the potential mechanisms underlying physiological regulation of phosphoinositide metabolism by other second-messenger pathways operative in this tissue. PMID- 7991646 TI - Tetanus toxin as a neurobiological tool to study mechanisms of neuronal cell death in the mammalian brain. AB - Tetanus toxin is a potent clostridial neurotoxin responsible for causing spastic paralysis in humans, often accompanied by seizures and death. The tetanic syndrome is believed to originate from a disinhibitory action of the toxin in the CNS. To produce its effects, tetanus toxin undergoes retrograde, intra-axonal transport to the CNS, where it blocks preferentially the release of gamma aminobutyric acid and glycine, two inhibitory neurotransmitters. These effects stem from the cleavage of synaptobrevin, a constitutive small-vesicle protein, by tetanus toxin, whose zinc-dependent metalloprotease characteristics recently have been recognized. Blockade of inhibitory transmission produces a predominance of excitatory amino acid neurotransmission, which is responsible for the neurodegenerative effect caused by tetanus toxin after intrahippocampal injection in rats. In fact, hippocampal damage can effectively be prevented by reduction of glutamate-mediated excitatory transmission, thus suggesting that unopposed excitation may be the underlying mechanism for neuronal cell death. PMID- 7991647 TI - Bioequivalence requirements for generic products. AB - Many countries have established procedures for the introduction of generic pharmaceutical products. In order to protect consumers, these generic products must be demonstrated to be therapeutically equivalent to a previously approved product, typically an innovator product. The therapeutic equivalence of a generic and an innovator product is most commonly based on the demonstration of bioequivalence, i.e. clinically insignificant differences in the rate and extent of drug absorption usually assessed from pharmacokinetic measurements. This article reviews the bioequivalence requirements for generic products and, in the interest of promoting international harmonisation, highlights those areas where differences exist among countries. PMID- 7991648 TI - Signalling pathways as targets for anticancer drug development. AB - Intracellular signalling pathways mediating the effects of oncogenes on cell growth and transformation offer novel targets for the development of anticancer drugs. With this approach, it may be sufficient to target a component of the signalling pathway activated by the oncogene rather than the oncogene product itself. In this review, the abilities of some antiproliferative drugs to inhibit signalling targets are considered. There are some anticancer drugs already in clinical trial that may act by inhibiting signalling targets, as well as drugs in preclinical development. Some problems that may be encountered in developing this new class of anticancer drugs are discussed. PMID- 7991649 TI - Targeting of drugs and vaccines to the gut. AB - Targeted delivery to the gastrointestinal tract requires a multi-disciplinary approach to research involving contributions from polymer and material scientists, gastroenterologists, pharmaceutical scientists and technologists. Intestinal delivery is important not only for drugs that act locally, but also for those with systemic activity. In particular, there is considerable interest in the oral delivery of peptides and it is felt that the colon may provide an advantageous absorption site for such molecules. The different targeting mechanisms available to the pharmaceutical scientist to provide site-specific delivery in the gastrointestinal tract will be critically assessed. Delivery systems and targeting agents, which are being developed for the delivery of drugs, may also be exploited for the delivery of vaccines, since many of the delivery problems are common to both areas. Recent developments in the design of oral antigen formulations will be discussed in this review. PMID- 7991651 TI - The use of splints in the treatment of joint stiffness: biologic rationale and an algorithm for making clinical decisions. AB - The purpose of this article are (1) to discuss the rationale for using splints to increase range of motion (ROM) and (2) to describe an algorithm that can guide therapists' clinical decisions when splints are used to treat patients who have limited ROM. The primary rationale for using splints is to apply relatively long periods of tensile stress to shortened connective tissues to induce tissue lengthening through biologic remodeling. The process of remodeling is contrasted with more temporary mechanical phenomena that occur in biologic tissues. The proposed algorithm guides the use of splints based on measurements of pain and ROM. We describe three variables of splint use that may be adjusted: frequency, duration, and intensity. The relative importance of each of these variables is discussed. The algorithm is not joint or injury specific and requires continual modification of splint use based on a patient's response to treatment. Deciding which patients are appropriate for end-range splinting and deciding when to discontinue splint use are also discussed. PMID- 7991650 TI - Relative effectiveness of an extension program and a combined program of manipulation and flexion and extension exercises in patients with acute low back syndrome. AB - BACKGROUND AND PURPOSE: The relative effectiveness of an extension program and a manipulation program with flexion and extension exercises was examined in patients with low back syndrome. SUBJECTS: Forty-nine patients with less than a 3 month history of low back pain were seen at physical therapy clinics in western Pennsylvania, southern Mississippi, and eastern Missouri during a 6-month period. Twenty-seven of the 49 patients were classified a priori into a treatment oriented category of extension/mobilization and were then randomly assigned to participate in an extension program or a program of manipulation followed by hand heel rocks (flexion and extension). Two patients dropped out of the study (1 patient returned to work, and the other patient was unable to comply with the treatment schedule), and 1 patient was eliminated from the study because of magnified illness behavior. The remaining 24 patients (15 male, 9 female; mean age = 44 years, SD = 15, range = 14-73) were assigned randomly and equally to the two groups. Eight physical therapists participated in the study. METHODS: A randomized clinical trial comparing the two regimens was conducted for a 1-week period. Outcome was assessed using an Oswestry Low Back Pain Questionnaire initially (before treatment) and at 3 and 5 days posttreatment, and data were analyzed using a 2 x 3 (group x time) analysis of variance. RESULTS: A significant interaction of the group and time variables was demonstrated, indicating that the rate of positive response was greater in the manipulation/hand-heel rock group than in the extension group. CONCLUSION AND DISCUSSION: In this category of patients with low back pain, the use of manipulation as an adjunct to an ongoing exercise program appears to be warranted. PMID- 7991652 TI - Effect of proprioceptive neuromuscular facilitation on the gait of patients with hemiplegia of long and short duration. AB - BACKGROUND AND PURPOSE: The immediate and cumulative effects of proprioceptive neuromuscular facilitation (PNF) applied to the pelvic region on the gait of patients with hemiplegia of short and long duration were studied. SUBJECTS: The subjects were 20 patients with hemiplegia of short duration (mean = 4.4 months, SD = 0.8, range = 2.8-5.6; n = 10) or long duration (mean = 15.4 months, SD = 1.7, range = 12.7-18.5; n = 10). METHODS: Each subject received a total of 12 sessions of PNF (three times per week), with each treatment lasting for 30 minutes. RESULTS: In subjects with hemiplegia of short duration, gait speed and cadence improved immediately after 1 session of PNF, and this improvement was further enhanced after 12 treatments. By contrast, subjects with hemiplegia of short duration. CONCLUSION AND DISCUSSION: These data suggest that (1) in both groups of patients with hemiplegia, the cumulative effects of PNF is more beneficial than the immediate effects, and (2) patients with hemiplegia of short duration respond to training sooner than do patients with hemiplegia of long duration, although the cumulative effects are similar for both groups. PMID- 7991653 TI - An exploratory study of righting reactions from a supine to a standing position in adults with Down syndrome. AB - BACKGROUND AND PURPOSE: Standing from a supine position is important for physical independence. The purpose of this study was to determine the developmental level of movement in this righting task of adults with Down syndrome. SUBJECTS: Fifteen subjects (mean age = 37.6 years, SD = 18, range = 22-65) with a diagnosis of Down syndrome and mild to moderate mental retardation participated in this study. METHODS: Subjects were videotaped rising from a supine to a standing position during 10 repeated trials. The video record was analyzed to categorize the standing movements according to VanSant's descriptions. RESULTS: Sixty-four percent of the upper-extremity movements, 14.6% of the axial component movements, and 33.8% of the lower-extremity movements could not be categorized according to VanSant's descriptions. Additionally, developmentally less advanced movements dominated those movements that could be categorized. CONCLUSION AND DISCUSSION: The great variety of movements demonstrated by these subjects in the task of standing from a supine position suggests greater motor maturity than is apparent from the movement sequences described by VanSant. Identifying appropriate standing movements in persons with Down syndrome will require weighing numerous intrinsic factors (eg, physiological and anthropometric) other than motor maturity. PMID- 7991654 TI - Evaluation of the gravity-correction feature of a Kin-Com isokinetic dynamometer. AB - BACKGROUND AND PURPOSE: Torques reflecting muscle performance must be corrected for the effects of gravity if error-free ratio-scaled data are to be obtained. Ratio-scaled data are necessary, for example, to report muscle performance characteristics in terms of ratios or percentages or in the form of ratios with another muscle (eg, ratio of hamstring to quadriceps femoris muscle peak torque). The purpose of this study was to determine the error associated with the gravity correction procedure of the Kin-Com dynamometer when a weight or limb segment is weighed at different lever arm positions. METHODS: A known weight was suspended from the lever arm of the Kin-Com dynamometer. The rotational component of gravitational forces on the weight was measured at 11 different angular positions. We compared the force measurement obtained from the Kin-Com with the predicted rotational component at each angular position. The gravitational forces on a subject's limb segment (leg) were then measured at 12 different angular positions in each of two trunk positions (sitting and supine). We compared the force measurement obtained from the Kin-Com with the predicted rotational component for each position. Forces measured for the two trunk positions with the lever arm horizontal were compared. Forces measured with the knee extended were compared with forces measured with the lever arm horizontal. RESULTS: The dynamometer accurately recorded the rotational component of gravitational forces for the weight suspended from the lever arm. There was a progressively greater discrepancy between measured forces and predicted forces for the leg as the lever arm was moved from horizontal to 50 degrees below the horizontal. The force recorded with the Kin-Com was greater when the subject's knee was in full extension than when the lever arm was horizontal, which placed the subject's knee in a flexed position. A small difference was noted between the measured forces with the lever arm horizontal when the subject was sitting compared with when the subject was positioned supine. CONCLUSION AND DISCUSSION: When weighing a leg with this dynamometer, we recommend that the lever arm be as close to the horizontal position as possible. Positions of proximal joints should be chosen that do not put two joint muscles in stretched positions. PMID- 7991655 TI - The influence of body size on linear measurements used to reflect cervical range of motion. AB - BACKGROUND AND PURPOSE: The purposes of the study were to demonstrate that linear measurements of cervical range of motion are confounded by differences in body size when comparisons are made between groups and to introduce an alternative measure of range of motion that adjusts for variation in body size. SUBJECTS: The sample consisted of 42 subjects (25 female, 17 male) with chronic posttraumatic headaches. METHODS: Using a tape measure, a physical therapist measured the distance between two anatomical landmarks with the subject's neck in the anatomical neutral position and with the subject's neck fully laterally flexed, rotated, and forward flexed. Range of motion was effected with two measurements: the distance between the landmarks at full flexion/rotation and the proportion of distance traversed between the landmarks. RESULTS: The end-of-range values were significantly correlated with body size. No significant correlations emerged between the proportion-of-distance values and body size. CONCLUSION AND DISCUSSION: Linear measurements of cervical motion are potentially confounded by body size when subjects of nonequivalent size are compared. Proportion-of distance measurement is presented as a more valid alternative to end-of-range measurement. PMID- 7991656 TI - Levels of reduction. PMID- 7991657 TI - Photosensitized formation of 8-hydroxy-2'-deoxyguanosine and DNA strand breakage by a cationic meso-substituted porphyrin. AB - Cationic porphyrins, known to have a high affinity for DNA, are useful tools with which to probe a variety of interactions with DNA. In this study we have examined both DNA strand scission and oxidative DNA base damage, measured by 8-hydroxy-2' deoxyguanosine (8-OHdG) formation, using a photoactivated cis-dicationic porphyrin. The data demonstrated a dose-dependent formation for each type of DNA damage. Inhibition of strand scission and 8-OHdG formation with the singlet oxygen scavenger 1,3-diphenylisobenzofuran and with MgCl2 and no apparent effect by D2O suggests that a singlet oxygen mechanism generated in close proximity to the DNA may be responsible for the damage. However, a nearly complete inhibition of 8-hydroxy-2'-deoxyguanosine formation in 75% D2O and the substantial enhancement of 8-hydroxy-2'-deoxyguanosine formation in a helium atmosphere by photoactivated porphyrin rules out singlet oxygen as a primary mechanism for this process. These data indicate that distinct mechanisms lead to 8-OHdG formation and strand scission activity. PMID- 7991658 TI - Femtosecond studies of hematoporphyrin derivative in solution: effect of pH and solvent on the excited state dynamics. AB - We report direct femtosecond measurements of the excited state dynamics of hematoporphyrin derivative (HpD) in solution. The dynamics are found to be very sensitive to the solvent and pH of aqueous solutions. The decay of the excited singlet states is much faster in acidic and pH 7 buffer aqueous solutions (< 230 ps) than in basic aqueous solutions or organic solvents (> 10 ns). The dynamical results show strong correlation with static fluorescence measurements: weaker fluorescence in acidic and pH 7 buffer solutions corresponding to shorter-lived excited states. A new fast decay component with a time constant around 5 ps is identified both in acidic aqueous solutions and in organic solvents such as acetone and attributed to internal conversion from the second to the first excited singlet state of aggregates or certain oligomers in HpD, in accord with the observation that the fast decay component is larger at a higher concentration. Oxygen is found to have no effect on the dynamics on the time scale investigated, 1 ns, indicating that oxygen quenching of the singlet excited states is insignificant on this time scale. The sensitive solvent and pH dependence of the excited state dynamics has important clinical implications in the use of HpD as a photosensitizing agent. PMID- 7991659 TI - Doubly allylic hydroperoxide formed in the reaction between sterol 5,7-dienes and singlet oxygen. AB - Ergosterol and 7-dehydrocholesterol, common 5,7-conjugated diene sterols, react with photochemically produced singlet oxygen very efficiently to yield, in parallel pathways, the corresponding 5,8-endoperoxides and the 7 beta-hydroperoxy 5,8(9),22-trienol or -5,8(9)-dienol, respectively. The hydroperoxides decompose in an acid-catalyzed reaction to generate hydrogen peroxide and the 5,7,9(11),22 tetraenol or 5,7,9(11) trienol, respectively, with 1:1 stochiometry. The molar ratio of endoperoxide to hydroperoxide was constant (16:5) with two different reaction solvents, two different photosensitizers, and at all time points between 5 min and 3 h from the start of irradiation. Ergosterol did not react with either hydrogen peroxide or superoxide ion under our reaction conditions. Inhibition studies with nitrogen, 2,5-dimethylfuran, beta-carotene, and tert-butanol confirmed the involvement of singlet oxygen in these reactions. The unstable hydroperoxide would be expected to have undesirable biological consequences if formed in vivo. PMID- 7991661 TI - Damage to uracil- and adenine-containing bases, nucleosides, nucleotides and polynucleotides: quantum yields on irradiation at 193 and 254 nm. AB - Photoreactions, such as base release and decomposition of the base moiety, induced by either 20 ns laser pulses at 193 nm or continuous 254 nm irradiation, were studied for a series of uracil and adenine derivatives in neutral aqueous solution. The quantum yield of chromophore loss (phi cl) depends significantly on the nature of the nucleic acid constituent and the saturating gas (Ar, N2O or O2). In the case of polynucleotides the destruction of nucleotides was measured by high-performance liquid chromatography after hydrolysis; the quantum yields (phi dn) are comparable to those of chromophore loss or larger. The phi cl and phi dn of 0.04-0.1 for poly(U) and poly(dU), obtained for both wavelengths of irradiation, are due to processes originating from the lowest excited singlet state, i.e. formation of photohydrates and photodimers, and a second part from photoionization using lambda irr = 193 nm. Irradiation at 193 nm effectively splits pyrimidine dimers and thus reverts them into monomers. The quantum yield for release of undamaged bases (phi br) from nucleosides, nucleotides and polynucleotides upon irradiation at 254 nm is typically phi br = (0.1-1) x 10( 4). Breakage of the N-glycosidic bond is significantly more efficient for lambda irr = 193 nm, e.g. phi br = 1.1 x 10(-3), 0.8 x 10(-3), 4.3 x 10(-3) and 0.5 x 10(-3) for poly(A), poly(dA), poly(U) and poly(dU) in Ar-saturated solution, respectively. Enhanced phi values for lambda irr = 193 nm, essentially for adenine and its derivatives, are caused by photoprocesses that are initiated by photoionization. PMID- 7991662 TI - Hematoporphyrin derivative (Photofrin) photodynamic action on Ca2+ transport in monkey kidney cells (CV-1). AB - After 24 h incubation with Photofrin (PF), photodynamic action has been studied on Ca2+ transport in CV-1 cells. A moderate increase of the cytosolic free Ca2+ concentration [Ca2+]i is observed immediately after a dose of irradiation which yields a survival rate of less than 5% at 48 h. In parallel, studies on digitonin permeabilized cells indicate that such a treatment inhibits endoplasmic reticulum Ca2+ uptake with few alterations of this process in mitochondria. In contrast, ADP-stimulated respiration is impeded and intracellular ATP level decreases. It is suggested that direct damage to endoplasmic reticulum as well as mitochondrial disturbance are the primary mechanisms responsible for a nontransient elevation of [Ca2+]i preceding cell death. PMID- 7991660 TI - Targeted photochemical modification of HIV-derived oligoribonucleotides by antisense oligodeoxynucleotides linked to porphyrins. AB - Antisense oligodeoxynucleotides directed against a 24-mer RNA derived from the long terminal repeat (LTR) region of HIV were linked to proto- and methylpyrroporphyrin and their zinc derivatives. The oligonucleotide-porphyrin conjugates were tested for their ability to induce photodamage on the target RNA. Upon hybridization followed by irradiation at 405 nm, the photochemical reaction led to photocross-linking of the antisense derivative to the RNA substrate. The protoporphyrin exhibited a much higher cross-linking yield than the methylpyrroporphyrin while the Zn-porphyrin derivatives were found to be less efficient than their corresponding nonmetallated congeners. The specificity of the photocross-linking reaction between the porphyrin-oligomer and its target RNA was demonstrated by the following evidence: (1) hybrid formation was required for photocross-linking to occur, (2) the sites of cross-linking on the target RNA were identified at G residues located in close proximity to the porphyrin photoactive center in the hybrid and (3) addition of bulk calf liver RNA did not affect the photocross-linking efficiency. PMID- 7991663 TI - Effects of in vitro exposure to ultraviolet radiation on the functional activity of lymphocytes, with emphasis on susceptibility of different species. AB - In this study lymphocytes from blood and/or spleen of different species (rat, mouse, human) were exposed to different doses of ultraviolet radiation (UVR). The functional activity of these lymphocytes was determined using assays for mitogen proliferation and the mixed lymphocyte response (MLR). These experiments demonstrated that in vitro exposure to UVR causes a dose-dependent decrease of the MLR activity of the irradiated lymphocytes. Viability of lymphocytes and mitogen proliferation responses were also decreased by UVR exposure but less severe in comparison to the MLR. Lymphocytes of rats seem to be more sensitive to UVR as compared to lymphocytes of mice and humans. PMID- 7991664 TI - Observed and predicted minimal erythema doses: a comparative study. AB - This study compared how well minimal erythema doses predicted using the reference action spectrum for UV erythema proposed by the International Commission on Illumination (CIE) in 1987 agreed with those observed in phototesting a large number of subjects with normal responses to sunlight to six different wavelengths of UV radiation (UVR) between 300 and 400 nm. It was found that, within the limits of experimental error, the hypothesis that the CIE reference action spectrum is a valid predictor of the erythemal effectiveness of different wavelengths of UVR could not be dismissed. There is no strong reason, therefore, why the CIE action spectrum should not continue to be used as a reference to compare the erythemal effectiveness of different broadband sources. However, close examination of the residuals from the regression analysis suggested that the erythemal sensitivity of skin at longer UV wavelengths (> 350 nm) in the population studied here is greater than predicted from the CIE reference action spectrum. PMID- 7991665 TI - Wavelength-dependent effects of benzoporphyrin derivative monoacid ring A in vivo and in vitro. AB - Benzoporphyrin derivative monoacid ring A (BPD-MA) is a chlorin-like photosensitizer currently in clinical trials for cancer and psoriasis. It has maximal absorption peaks at both 630 and 690 nm and can be activated at both these wavelengths. In vitro phototoxicity tests using the P815 murine mastocytoma cell lines conducted over wavelengths of light between 678 and 700 nm emitted by an argon-ion pumped dye laser showed that equivalent cell kill could be achieved between 682 and 690 nm. Tests on in vivo phototoxicity of normal skin of DBA/2 mice injected with 2 mg/kg of BPD-MA and exposed to light at 125 J/cm2, between 620 and 700 nm, demonstrated peaks of normal skin damage occurring at 630-640 nm and 680-690 nm. In tests carried out with light between 620 and 700 nm, at 10 nm increments, it was seen that light delivered at 680-690 nm caused slightly more damage to normal skin than light delivered at 630-640 nm. When lower doses of light between 675 and 705 nm were tested using smaller increments, it was determined that equivalent skin damage occurred over a range of 680-695 nm. Antitumor efficacy in tumor-bearing DBA/2 mice was tested between 683 and 695 nm. It was found that equivalent antitumor efficacy, determined by assessing tumor free status at 20 days posttreatment, occurred at wavelengths between 685 and 693 nm.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7991666 TI - Shape of the chromophore binding site in pharaonis phoborhodopsin from a study using retinal analogs. AB - To investigate the shape of the chromophore binding site of pharaonis phoborhodopsin (ppR), ppR-opsin was incubated with five ring-modified retinal analogs: an acyclic retinal, phenylretinal, alpha-retinal, cyclohexylretinal and 5-isopropyl-alpha-retinal. The experimental results were compared with those obtained from bacteriorhodopsin-opsin (bR-opsin) and the same retinal analogs. It was suggested that ring chain conformation is important in affecting the spectral shoulder unique for the absorption spectrum of ppR. The rate of pigment formation depended greatly on the analogs used with the planar analogs showing rapid formation. Thus, we concluded that the space of the retinal binding site of ppR is restricted to the plane of the cyclohexenyl ring of the chromophore, whereas that of bR is less restricted. PMID- 7991667 TI - IS1139 from Streptococcus salivarius: identification and characterization of an insertion sequence-like element related to mobile DNA elements from gram-negative bacteria. AB - An insertion sequence-like element, IS1139, was cloned and sequenced from Streptococcus salivarius ATCC 25975 chromosome. This insertion sequence-like element is 1168 bp long and is delimited by inverted repeats of 29 bp and by a duplicated sequence of 6 bp. This IS possesses an open reading frame that codes for a putative transposase of 339 amino acids which has, respectively, 94, 35, 33, and 30% amino-acid identity with the transposases of IS1161 from S. salivarius ATCC 25975, IS4351 from Bacteroides fragilis, IS30 from Escherichia coli, and IS1086 from Alcaligenes eutrophus. Sequence analysis revealed that these transposases may have evolved from a common ancestral gene. Southern hybridization of restriction endonuclease-digested genomic DNA from 21 strains of oral streptococci, using a probe specific to the transposase-encoding gene (tnpA), revealed that IS1139 is found in two strains of S. salivarius, ATCC 25975 and ATCC 13419, in eight and two copies, respectively. PMID- 7991668 TI - Nucleotide sequence and analysis of an insertion sequence from Bacillus thuringiensis related to IS150. AB - A 5.8-kb DNA fragment encoding the cryIC gene from Bacillus thuringiensis (Bt) subsp. aizawai HD229 was subcloned into the pMex7 vector for expression in Escherichia coli. In addition to the 135-kDa CryIC delta-endotoxin, this DNA fragment also encoded a 30-kDa polypeptide whose open reading frame (orfX) was located less than 200 bp upstream of cryIC. Nucleotide sequencing showed that orfX was truncated at the 5' end, and full sequence was obtained from a second overlapping clone. Sequence analysis showed that orfX could encode a polypeptide closely related to the putative transposase from IS150. OrfX was flanked by a 17 bp imperfect inverted repeat, defining the length of the element as 998 bp. Southern blot analysis revealed that the novel insertion sequence was present in a single copy and located in an identical position immediately upstream of cryIC in plasmid DNA from both Bt subsp. aizawai and entomocidus. PMID- 7991669 TI - TrfA-dependent, inner-membrane-associated plasmid RK2 DNA synthesis in Escherichia coli maxicells. AB - Previous results of experiments in which plasmid-encoded proteins were selectively labeled in ultraviolet sensitive "maxicell" mutants suggested that the essential initiation proteins of RK2 (33 and 43 kDa) were bound to the inner membrane of Escherichia coli (D. Kostyal et al., 1989, Plasmid 21, 226-237). However, in the present studies using a specific polyclonal antibody against the TrfA initiation proteins, significant levels of these proteins were also detected for the first time in the outer membrane fraction as well as the inner membrane fraction. Only in the cytosol fraction were the initiation proteins relatively absent. In order to determine whether initiation and replication were also associated with either or both of the membrane fractions, it was necessary to develop a replicating system more active than the one previously extracted from minicell membranes, which did not separate the membrane into its component parts (J. A. Kornacki and W. Firshein, 1986, J. Bacteriol. 167, 319-326). In addition, it was also necessary to devise an extraction procedure that did not degrade the supercoil DNA template during the separation of the inner from the outer membrane fraction. Both criteria were met, first by the use of maxicells containing a miniplasmid derivative of RK2 and second by disrupting cell envelopes in the French pressure cell using low pressure. Under these conditions, not only were the two major membrane fractions separated successfully from the cytosol fraction, but supercoil DNA template was also preserved in both fractions, detergents were avoided, and replication was significantly higher than that described in the earlier experiments. TrfA-dependent initiation of DNA replication was associated primarily with the inner membrane fraction. PMID- 7991670 TI - A set of beta-galactosidase gene fusion cassettes demonstrates usefulness in expressing HIV-1 genes in Escherichia coli. AB - Heterologous expression in Escherichia coli is often limited by yield and solubility of the foreign protein in the bacterial cytoplasm. In many cases, overexpression also results in growth inhibition. In order to produce retroviral proteins that are especially difficult to overexpress in E. coli, we designed a set of beta-galactosidase fusion cassettes. Fusions with beta-galactosidase increase significantly both yield and solubility of the foreign proteins, thus making purification much easier. These cassettes allow for N- or C-terminal fusions, and the retroviral proteins can be released from the fusion by automaturation in vivo for the HIV-1 protease or cleavage by thrombine for Tat. More generally, any synthetic sequence coding for a given cleavage site can be introduced 5' or 3' to the lacZ gene through a convenient set of unique restriction sites, making these fusion cassettes highly versatile. PMID- 7991671 TI - Reiterated sequences of the Streptomyces griseus plasmid pSG1. AB - pSG1 is a 16.9-kb element that is comaintained with its chromosomally integrated form in Streptomyces griseus YP5344. Three forms of amplifiable units of DNA (AUDs) were found on pSG1 in S. griseus YP5344 derivatives. All three share a 3.1 kb fragment, but each AUD is flanked by different sequences. Fragments bracketing the AUDs on pSG1 and fragments of junctions between the AUDs from amplifiable DNA sequences (ADS) containing pSG1 derivatives were cloned and sequenced. The edges of the AUDs are not homologous, nor are they flanked by direct repeats. One AUD is bracketed by a short (8-nt) inverted repeat. This AUD was reiterated in six independent isolates, suggesting preferred sites for the reiteration mechanism. Cells harboring plasmids with ADS also harbor circular molecules consisting of the same AUD. These findings suggest that reiteration is initiated by an illegitimate recombination event that yields an AUD duplication on the plasmid or an AUD DNA circle. Either of these structures may serve as an intermediate in the reiteration process. Circular AUDs may also be formed by intramolecular recombination between the repeats during the process of deamplification. PMID- 7991672 TI - IS1032 from Acetobacter xylinum, a new mobile insertion sequence. AB - IS1031 elements constitute a family of related insertion sequences (IS) in Acetobacter xylinum strains. A new IS1031-related element, IS1032, was isolated from A. xylinum ATCC 23770. Southern hybridization analysis showed that one or more sequences similar to IS1032 are present in most of the A. xylinum strains examined. In addition, one copy was detected in Acetobacter aceti ATCC 15973. The transposition of IS1032 was evident from the appearance of an extra insertion in a spontaneous exopolysaccharide-negative mutant of A. xylinum ATCC 23770. IS1032 consists of 916 bp and has imperfect terminal inverted repeats of 14 bp (IR-Left) and 16 bp (IR-Right). A 3-bp target sequence is duplicated upon insertion. IS1032 displays a single open reading frame, encoding a putative 276-amino-acid protein sharing 58% identity with the corresponding protein encoded by IS1031. Thus, IS1032 is a member of the IS1031 family in A. xylinum. A striking degree of nucleotide sequence similarity between IS1032 and ISRm4 from Rhizobium meliloti was found. Furthermore, the IS1031-family transposases also display stretches of amino acid sequence similarities with putative transposases encoded by IS elements from other species. PMID- 7991673 TI - Complete nucleotide sequence of the Streptomyces nigrifaciens plasmid, pSN22: genetic organization and correlation with genetic properties. AB - The complete nucleotide sequence of the multicopy, self-transmissible, broad-host range Streptomyces plasmid pSN22, originating from Streptomyces nigrifaciens, was determined. pSN22 is a circular DNA molecule, 10,922 bp with 71.76% G + C. Computer-assisted analysis identified 10 open reading frames (ORFs); 8 of them- traA (155 amino acids [aa], traB (651 aa), traR (246 aa), spdB1 (107 aa), spdB2 (251 aa), spdB3 (70 aa), spdB4 (128 aa) and spdA (154 aa)--are involved in plasmid transfer and pock-formation. One ORF, rep (451 aa), probably encodes a replication protein similar to known replication proteins of rolling circle replicons. The four spdB genes have hydrophobic amino termini that might attach to the cytoplasmic membrane. The deduced rep proteins of pSN22 and pIJ101 are very similar, suggesting that both are derived from a recent common ancestor. The transfer regions of the two plasmids are, however, very different. The only detectable similarities between presumably analogous proteins are DNA- and NTP binding motifs and hydrophobic regions. This suggests that two transfer regions are of separate origins. PMID- 7991674 TI - An EBV-based vector allowing a high level of LTRHIV-directed expression in human cells. AB - We have developed a vector that allows high and transactivable expression of inserted genes. The vector contains a transcription unit in which the LTR from HIV flanks a multicloning site. The plasmid is based on the EBV p205 plasmid, which allows stable replication in human cells. The ability of the vector to express an exogenous DNA in human cells has been tested using the firefly luciferase gene. PMID- 7991675 TI - The large nonsymbiotic plasmid pRmeGR4a of Rhizobium meliloti GR4 encodes a protein involved in replication that has homology with the RepC protein of Agrobacterium plasmids. AB - The large plasmid, pRmeGR4a, of Rhizobium meliloti GR4 is a nonsymbiotic, self transmissible replicon that shows a high degree of stability. Plasmid replication and stabilization functions are located on a 4.8-kb PstI fragment. Analysis of the nucleotide sequence of this DNA region revealed the presence of six open reading frames (ORFs) with coding capabilities; all are transcribed in the same direction. Only one of the ORFs (ORF3) seems to be essential for replication. Its predicted protein sequence shows homology with RepC, a protein that has been suggested to be involved in the replication of Agrobacterium Ri and Ti plasmids. PMID- 7991676 TI - Surface exclusion gene of IncI1 plasmid R64: nucleotide sequence and analysis of deletion mutants. AB - We have cloned and sequenced the exc gene determining surface exclusion of IncI1 plasmid R64. R64 exc gene is highly homologous to the R144 exc gene. The R64 exc gene may encode two proteins with 220 and 147 amino acid residues by inframe reinitiation of translation, as the R144 exc gene does, while the larger protein with 220 amino acids was shown to be essential for surface exclusion function. R64 derivatives carrying deletion or insertion mutations in the exc gene transferred at a frequency similar to that of wild-type R64, indicating that the exc gene is not essential for the transfer of R64. PMID- 7991677 TI - Transformation of Mollicutes with single-stranded Tn4001 DNA. AB - Acholeplasma oculi ISM1499 and Mycoplasma gallisepticum were transformed with single-stranded and double-stranded plasmids containing Tn4001. The transposon mobilized to the chromosome using both single-stranded and double-stranded DNA at the same frequency. M. gallisepticum transformed at a 2 log lower frequency than did A. oculi ISM1499. Restriction enzyme digestion of single-stranded DNA indicated homologous base pairing in the inverted repeat regions, which could account for the transpositional activity of single-stranded DNA. PMID- 7991678 TI - Tn5431, a new transposable element composed of Tn1721- and Tn3-like genes. PMID- 7991679 TI - Seed-specific gene activation mediated by the Cre/lox site-specific recombination system. AB - The Cre/lox site-specific recombination system was used to activate a transgene in a tissue-specific manner. Cre-mediated activation of a beta-glucuronidase marker gene, by removal of a lox-bounded blocking fragment, allowed the visualization of the activation process. By using seed-specific promoters, the timing and efficiency of gene activation could be followed within the developing tobacco (Nicotiana tabacum) embryo. To serve as a basis for analyzing gene expression after-Cre-mediated activation, the timing and patterns of expression of the promoters of the genes encoding French bean (Phaseolus vulgaris) beta phaseolin and the alpha' subunit of soybean (Glycine max) beta-conglycinin, as well as the cauliflower mosaic virus 35S promoter, were studied in developing transgenic tobacco embryos using the same visual marker. These seed-specific promoters were expressed earlier than anticipated. The 35S promoter was expressed earlier than the seed-specific promoters, but not in globular-stage embryos. Cre mediated gene activation occurred approximately 1 d after promoter activation, based on developmental staging, and spread progressively throughout the embryo. The timing of gene activation was varied by altering Cre expression. Efficient Cre expression ultimately directed gene activation throughout the model tissue, whereas inefficient Cre expression resulted in mosaic tissue. Limited gene activation provides a system for cell lineage and developmental analyses. PMID- 7991680 TI - 5' proximal regions of Arabidopsis nitrate reductase genes direct nitrate-induced transcription in transgenic tobacco. AB - Nitrate reductase (NR) is the first enzyme in nitrate assimilation, a critical process for plant survival. The regulation of NR gene expression is complex, involving both internal and external factors. Of these, nitrate induction of NR gene expression has been studied most extensively and is well conserved among bacteria, fungi, and higher plants. We are interested in understanding the mechanism of nitrate induction of higher plant NR genes. Here we describe promoter analyses of the 5' flanking regions of the Arabidopsis NR genes, NR1 and NR2, with respect to nitrate induction of gene expression. To facilitate these analyses, a nitrate induction procedure using T1 transgenic tobacco plants was established. Approximately 1.5-kb 5' flanking regions of the two Arabidopsis NR genes (NR1 and NR2) were fused to a reporter gene and its expression in transgenic plants was analyzed. Deletion analyses of these regions show that 238- and 188-bp 5' flanking regions of the NR1 and NR2, respectively, contain sequences responsive to nitrate induction. PMID- 7991681 TI - Cloning and regulation of flavonol 3-sulfotransferase in cell-suspension cultures of Flaveria bidentis. AB - Flaveria spp. accumulate flavonol sulfate esters whose biosynthesis is catalyzed by a number of position-specific flavonol sulfotransferases. Although the accumulation of sulfated flavonols appears to be tissue specific and developmentally regulated and to vary among related species, little is known about the mechanism of regulation controlling the synthesis of these metabolites. In the present work, we report the isolation of a cDNA clone from Flaveria bidentis (pBFST3) encoding flavonol 3-sulfotransferase (F3-ST), which catalyzes the first step in the biosynthesis of flavonol polysulfates. This clone (pBFST3) was expressed in Escherichia coli and produced an F3-ST with high affinity for the flavonol aglycones, quercetin, and its 7-methyl derivative, rhamnetin. In addition, the synthetic auxin 2,4-dichlorophenoxyacetic acid was shown to induce F3-ST enzyme activity and F3-ST mRNA transcript levels in cell cultures of F. bidentis. The F3-ST mRNA levels increased within the first 3 h, reaching a maximum after 24 h of treatment, and remained elevated for up to 48 h. Treatments with either quercetin 3-sulfate or quercetin 3,7,4'-trisulfate reduced F3-ST enzyme activity in cell cultures but had no effect on the transcript levels. These results are discussed in relation to the putative role of flavonoid conjugates in the regulation of auxin transport. PMID- 7991682 TI - Apple beta-galactosidase. Activity against cell wall polysaccharides and characterization of a related cDNA clone. AB - A beta-galactosidase was purified from cortical tissue of ripe apples (Malus domestica Borkh. cv Granny Smith) using a procedure involving affinity chromatography on lactosyl-Sepharose. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis indicated that two polypeptides of 44 and 32 kD were present in the fraction that showed activity against the synthetic substrate p-nitrophenol beta-D-galactopyranoside. The enzyme preparation was incubated with polysaccharide extracts from apple cell walls containing beta-(1-->4)-linked galactans, and products of digestion were analyzed by gas chromatography. Small amounts of monomeric galactose were released during incubation, showing that the enzyme was active against native substrates. Amino acid sequence information was obtained from the purified protein, and this showed high homology with the anticipated polypeptide coded by the ethylene-regulated SR12 gene in carnation (K.G. Raghothama, K.A. Lawton, P.B. Goldborough, W.R. Woodson [1991] Plant Mol Biol 17: 61-71) and a harvest-related pTIP31 cDNA from asparagus (G. King, personal communication). Using the asparagus cDNA clone as a probe, an apple homolog (pABG1) was isolated. This clone contains a 2637-bp insert, including an open reading frame that codes for a polypeptide of 731 amino acids. Cleavage of an N-terminal signal sequence would leave a predicted polypeptide of 78.5 kD. Genomic DNA analysis and the isolation of other homologous apple clones suggest that pABG1 represents one member of an apple beta-galactosidase gene family. Northern analysis during fruit development and ripening showed accumulation of pABG1-homologous RNA during fruit ripening. Enzyme activity as measured in crude extracts increased during fruit development to a level that was maintained during ripening. PMID- 7991683 TI - Assessment of the number and expression of P-type H(+)-ATPase genes in tomato. AB - Seven genomic fragments encoding isoforms of tomato (Lycopersicon esculentum) plasma membrane H(+)-ATPase were cloned and characterized. Genomic DNA gel-blot analysis indicated that probes corresponding to LHA1 through LHA7 hybridized to a common set of seven to nine restriction fragments at moderate stringency and to single, distinct fragments at high stringency. RNA gel-blot and polymerase chain reaction (PCR)-based RNA analyses indicated that LHA1, LHA2, and LHA4 transcripts were present in all organs examined (roots, hypocotyls, stems, immature leaves, mature leaves, green fruit, and red ripe fruit). LHA1 mRNA was present at similar abundance in all organs, LHA2 mRNA was most abundant in hypocotyls and leaves, and LHA4 mRNA was most abundant in roots and hypocotyls. RNA gel-blot and RNA based PCR assays indicated that LHA3, LHA5, LHA6, and LHA7 mRNA was present at very low or nondetectable levels in all organs, suggesting that these genes are either expressed at very low levels or in organs not examined or that they are regulated by hormonal or environmental cues that were not tested. Indoleacetic acid (IAA) treatment of tomato hypocotyl segments resulted in modest changes in abundance of LHA1, LHA2, and LHA4 transcripts, but these changes were not correlated with the time course of IAA-induced growth. In addition, constitutively silent LHA genes were not activated by IAA. These results indicate that at least seven genomic sequences are present in tomato that may encode plasma membrane H(+)-ATPases, at least three of which are expressed relatively abundantly at the mRNA level. PMID- 7991684 TI - A group of chromosomal proteins is specifically released by spermine and loses DNA-binding activity upon phosphorylation. AB - Biologically relevant concentrations as low as 500 microM spermine led to the specific release of chromatin-associated proteins from nuclei of rice (Oryza sativa) seedlings. Using a southwestern technique, it was shown that several of these proteins bind DNA. This affinity was lost upon in organello phosphorylation by an endogenous kinase. The effect of spermine was very specific. Spermidine was far less effective and putrescine was essentially ineffective in releasing these proteins. The most abundant spermine-released protein was shown to be homologous to the maize HMG1 protein. Our results suggest that spermine induces the release of spermine-released proteins by changing DNA conformation. Binding of these proteins might be sensitive to long-range changes in chromosome structure caused by torsional stress. PMID- 7991685 TI - Identification of surface-exposed domains on the reducing side of photosystem I. AB - Photosystem I (PSI) is a multisubunit enzyme that catalyzes the light-driven oxidation of plastocyanin or cytochrome c6 and the concomitant photoreduction of ferredoxin or flavodoxin. To identify the surface-exposed domains in PSI of the cyanobacterium Synechocystis sp. PCC 6803, we mapped the regions in PsaE, PsaD, and PsaF that are accessible to proteases and N-hydroxysuccinimidobiotin (NHS biotin). Upon exposure of PSI complexes to a low concentration of endoproteinase glutamic acid (Glu)-C, PsaE was cleaved to 7.1- and 6.6-kD N-terminal fragments without significant cleavage of other subunits. Glu63 and Glu67, located near the C terminus of PsaE, were the most likely cleavage sites. At higher protease concentrations, the PsaE fragments were further cleaved and an N-terminal 9.8-kD PsaD fragment accumulated, demonstrating the accessibility of Glu residue(s) in the C-terminal domain of PsaD to the protease. Besides these major, primary cleavage products, several secondary cleavage sites on PsaD, PsaE, and PsaF were also identified. PsaF resisted proteolysis when PsaD and PsaE were intact. Glu88 and Glu124 of PsaF became susceptible to endoproteinase Glu-C upon extensive cleavage of PsaD and PsaE. Modification of PSI proteins with NHS-biotin and subsequent cleavage by endoproteinase Glu-C or thermolysin showed that the intact PsaE and PsaD, but not their major degradation products lacking C-terminal domains, were heavily biotinylated. Therefore, lysine-74 at the C terminus of PsaE was accessible for biotinylation. Similarly, lysine-107, or lysine-118, or both in PsaD could be modified by NHS-biotin. PMID- 7991686 TI - Purification and partial characterization of NADPH-cytochrome c reductase from Petunia hybrida flowers. AB - NADPH-cytochrome c reductase was solubilized from the microsomal fraction of Petunia hybrida flowers by 3-[(3-cholamidopropyl)dimethylammonio]-1-propane sulfonate detergent and purified by adenosine 2',5'-bisphosphate-Sepharose chromatography, followed by high-performance anion-exchange chromatography. Two proteins with molecular sizes of 75 and 81 kD were detected in the purified preparation by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Western blot analysis showed that both purified proteins cross-reacted with two different monoclonal antibodies raised against P. hybrida NADPH-cytochrome c reductase and rabbit anti-Jerusalem artichoke NADPH-cytochrome P450 reductase antibodies. Only one 84-kD protein was detected by western blot analysis of fresh microsomal extracts. Amino acid sequence analysis of tryptic peptides revealed significant similarity to the NADPH binding region of plant and animal NADPH-cytochrome P450 reductases and Bacillus megaterium cytochrome P450:NADPH-cytochrome P450 reductase. The pH optimum for reduction of ferricytochrome c was 7.4 and the Km values for the binding of NADPH and ferricytochrome c were 9.2 and 2.8 microM, respectively. We believe that the purified enzyme is a P. hybrida NADPH cytochrome P450 reductase (EC 1.6.2.4). PMID- 7991687 TI - Purification and characterization of two ferredoxin-NADP+ oxidoreductase isoforms from the first foliage leaves of mung bean (Vigna radiata) seedlings. PMID- 7991688 TI - Posttranslational modification of an isoinhibitor from the potato proteinase inhibitor II gene family in transgenic tobacco yields a peptide with homology to potato chymotrypsin inhibitor I. AB - A member of the potato proteinase inhibitor II (PPI-II) gene family under the control of the cauliflower mosaic virus 35S promoter has been introduced into tobacco (Nicotiana tabacum). Purification of the PPI-II protein that accumulates in transgenic tobacco has confirmed that the N-terminal signal sequence is removed and that the inhibitor accumulates as a protein of the expected size (21 kD). However, a smaller peptide of approximately 5.4 kD has also been identified as a foreign gene product in transgenic tobacco plants. This peptide is recognized by an anti-PPI-II antibody, inhibits the serine proteinase chymotrypsin, and is not observed in nontransgenic tobacco. Furthermore, amino acid sequencing demonstrates that the peptide is identical to a lower molecular weight chymotrypsin inhibitor found in potato tubers and designated as potato chymotrypsin inhibitor I (PCI-I). Together, these data confirm that, as postulated to occur in potato, PCI-I does arise from the full-length PPI-II protein by posttranslational processing. The use of transgenic tobacco represents an ideal system with which to determine the precise mechanism by which this protein modification occurs. PMID- 7991689 TI - Carbon starvation increases endoglycosidase activities and production of "unconjugated N-glycans" in Silene alba cell-suspension cultures. AB - We previously reported the occurrence of oligomannosides and xylomannosides corresponding to unconjugated N-glycans (UNGs) in the medium of a white campion (Silene alba) cell suspension. Attention has been focused on these oligosaccharides since it was shown that they confer biological activities in plants. In an attempt to elucidate the origin of these oligosaccharides, we studied two endoglycosidase activities, putative enzymes involved in their formation. The previously described peptide-N4-(N-acetyl-glucosaminyl) asparagine amidase activity and the endo-N-acetyl-beta-D-glucosaminidase activity described in this paper were both quantified in white campion cells during the culture cycle with variable initial concentrations of sucrose. The lower the sucrose supply, the higher the two activities. Furthermore, endoglycosidase activities were greatly enhanced after the disappearance of sugar from the medium. The production of UNGs in the culture medium rose correlatively. These data strongly suggest that the production of UNGs in our white campion cell-suspension system is due to the increase of these endoglycosidase activities, which reach their highest levels of activity during conditions of carbon starvation. PMID- 7991690 TI - Three different cDNAs encoding acyl carrier proteins from Cuphea lanceolata. PMID- 7991691 TI - A third highly conserved group 1 Lea gene from Arabidopsis thaliana L. PMID- 7991692 TI - Sequence of the phytoene desaturase locus of tomato. PMID- 7991693 TI - Isolation and characterization of a rice full-length cDNA clone encoding a polyubiquitin. PMID- 7991695 TI - A ompR gene in the plastid genome of Rhodella violacea. PMID- 7991694 TI - A gene encoding acetyl-coenzyme A carboxylase from Brassica napus. PMID- 7991696 TI - A 1-aminocyclopropane-1-carboxylate oxidase cDNA sequence from Pelargonium. PMID- 7991697 TI - Sequence of a cDNA from Oryza sativa (L.) encoding the pyruvate decarboxylase 1 gene. PMID- 7991698 TI - Cloning of a cDNA encoding 3-ketoacyl-acyl carrier protein synthase III from Arabidopsis. PMID- 7991699 TI - Detection and sequencing of the transposable element ILS-1 in the Illinois long term selection maize strains. PMID- 7991700 TI - Isolation and characterization of a drought-induced soybean cDNA encoding a D95 family late-embryogenesis-abundant protein. PMID- 7991701 TI - cDNAs for isoforms of the delta 9-stearoyl-acyl carrier protein desaturase from Thunbergia alata endosperm. PMID- 7991702 TI - A cDNA encoding a new GTP-binding protein of the ADP-ribosylation factor family from Arabidopsis. PMID- 7991703 TI - A cDNA encoding a low molecular mass heat-shock protein from opium poppy. PMID- 7991704 TI - The PHYC gene of Arabidopsis. Absence of the third intron found in PHYA and PHYB. PMID- 7991705 TI - Nucleotide sequence of a cDNA encoding a heat-shock protein (HSP70) from barley (Hordeum vulgare L.). PMID- 7991706 TI - [The dynamics of depression on children. A prospective follow-up study]. AB - Prospective follow-up study of a group of 33 children diagnosed as socially and emotionally immature, and depressive at age 7 years were conducted. Results of assessment at 10 years of age revealed chronicity of depression in this group. Chronicity of depression was reflected in the change of symptomatology. The thesis about the dependence of depressive symptoms on the developmental stage was supported. Answers to the question about the nature of childhood depression should be looked for in farther longitudinal studies. PMID- 7991707 TI - [Description of an adolescent psychiatric inpatients' families]. AB - Detailed analysis of family dynamics of 63 adolescent psychiatric in-patients' families was carried out. The results of this project show indicate relatively more dysfunctional relations of the patient with other family members, especially with both parents. Also the study showed undifferentiated needs of family members' for co-operation and support from the psychiatric institution. Attitudes of resistance and anxiety in relation to psychiatry, which are still typical for Polish families at the end of eighties, were indicated. PMID- 7991708 TI - [Anxiety in the family]. AB - The authors present the conceptual framework of the development and transmission of anxiety in the family system based on M. Bowen and general system theories. Anxiety is conceptualized as the reaction of family members to the disturbance in relational balance within the family system. The hypothesis that blurred boundaries within the family system are responsible for development, transmission and maintenance of anxiety in the family system is presented and supported with clinical examples. The ways of transmission of anxiety within the nuclear family and the phenomenon of transgenerational transmission are described. At the end the authors discussed practical implications of the presented theory for family therapy. Work with families with high level of anxiety should support the development of clear boundaries within the family system which leads to processes of separation and autonomy of family members. PMID- 7991709 TI - [Panic disorders of children: personal observation]. AB - Two children with panic disorder (PD) have been presented: 12 year old boy and 9.5 year old girl. PD diagnosis was based on diagnostic criteria DSM-III-R. According to the literature a fully developed PD appears mainly after the 20th year of life. There is no mention made about PD relating to children. Our observations indicate that PD may appear as early as the 10th year of life. Analysis of these cases may support other authors' findings confirming that: etiopathogenesis of PD has a multifactor nature and psychodynamic mechanisms play a role in its apparition [13, 17]; release mechanism of panic reaction may be based on conscious or unconscious stimulation to day-dreaming, especially together with negative effect [17]. Positive therapeutic result may be obtained by use of pharmacotherapy along with psychotherapy [4, 16, 18]. PMID- 7991710 TI - [Premorbid adjustment of 100 hospitalized adolescent patients]. AB - Premorbid adjustment of 100 hospitalized adolescent patients and its correlation with some clinical variables was assessed and compared with a group of 100 healthy adolescents. The hospitalized group of patients was divided into four diagnostic subgroups according to the diagnostic criteria of ICD 9: psychoses, neuroses, conduct and personality disorders and anorexia nervosa. The following assessment tools were used: Premorbid Adjustment Scale in Polish adaptation of A. Grzywa, List of demographic variables, List of Organic Risk Factors, Inventory of Developmental Psychopathology and the Brief Psychiatric Research Scale (BPRS). SPSS was used to analyze the results. The results confirmed the hypothesis of different levels of premorbid adjustment in hospitalized and healthy adolescents as well as in hospitalized adolescents and original control group of the research of A. Grzywa. Contrary to our expectations and data from the literature premorbid adjustment was lowest in the group of patients with conduct disorders and not as was expected in the group of psychotic adolescents. It was also confirmed that the differences in the level of premorbid adjustment between the group of hospitalized adolescents and control groups were smaller in the period of early childhood than in later developmental periods. Pronounced difficulties in adjustment were observed in all diagnostic subgroups in the period of late adolescence. PMID- 7991711 TI - [Selected issues of biological aspects of eating disorders]. AB - This paper reviews the recent progress in the understanding of the neurobiology of the eating disorders. The analysis of the biochemical abnormalities present in the patients with bulimia nervosa indicates the decrease of central serotonin and noradrenalin activity, elevation of the levels of cerebrospinal fluid peptide YY, alterations of the endogenous opioids and also reduction of peripheral cholecystokinin levels. As these studies were performed on patients who were actively binging and purging it is conceivable that the above abnormalities can results from a pathological feeding pattern. It is also suggested that the reduction of central serotoninergic activity is the stable, trait-related dysregulation of neurotransmitter system activity. In patients with anorexia nervosa the endocrine disturbances of the hypothalamic-pituitary-ovarian and hypothalamic-pituitary-adrenal axes were thoroughly studied. Underweight anorectic patients have been found to have elevations of cerebrospinal fluid level of neuropeptide Y, corticotropin releasing hormone and vasopressin as well as reductions of beta-endorphin and oxytocin level. However, most of the neuropeptide alterations normalize following weight recovery. The only exception is a persistent increase of central serotonin activity postulated to be responsible for the obsessive-compulsive personality traits and disturbed eating behaviors found in these patients. PMID- 7991712 TI - [Clinical evaluation of fluoxetine]. AB - The multicenter trials were performed in a group of 86 depressive inpatients (among them 64 with endogenous depression) managed with fluoxetine (Prozac). It was established that the drug is most effective in managing psychogenic depressions and may also be of use in endogenous depressions, among them in drug resistant ones. Tolerance to the drug was satisfactory, 62% did not show any unwanted side-effects. The rest of the group displayed sleep disorders, increased anxiety, lost of appetite and nausea. Changes in the laboratory parameters and non-specific changes in the electrocardiogram were observed sporadically. Fluoxetine seemed not to have any direct cholinolytic effect. PMID- 7991713 TI - [Clomipramine and other serotonin reuptake inhibitors in the treatment of depressed mood, anxiety and impaired impulse control]. AB - The antidepressive effects of substances which most likely increase the rate of monoaminergic neurotransmission by the antagonization of the serotonin and noradrenaline reuptake inhibitors has been know to exist for over thirty years. The role of both of these substances, serotonin and noradrenaline, in the function of these mechanisms is still, however, a matter of discussion. In the last ten years it has been shown that many antidepressive drugs are not only effective in the treatment of depression but also in the treatment of many other psychiatric disorders. These include for example panic anxiety attacks, compulsive-obsessive symptoms, premenstrual tension disorder etc. It appears from the treatment of these disorders that serotonin is of greater importance than noradrenaline. PMID- 7991714 TI - [Procaine kindling in acute non-allergic reaction to procaine penicillin G]. AB - On the basis of the analysis of acute nonallergic reaction to a course of procaine penicillin G, the authors have stated that symptoms of this reaction result from the irritation of temporal limbic structures. The authors think that it is connected with procaine kindling mechanism, the procaine component of the drug. PMID- 7991715 TI - [Hoigne syndrome and psychopathological issues]. AB - This paper presents 3 cases of late psychopathological issues after the Hoigne syndrome. Acute egzogenous psychosis caused the anxiety-like disorder and was the reason for an endogenous psychosis of with a schizophrenia profile. There is a need for psychiatric care support in every case of Hoigne syndrome after acute episode of mental disturbance. PMID- 7991717 TI - Opportunities for women through reproductive choice. AB - Women around the world hope for the future--for better lives for themselves, education and prosperity for their children, and security for their families. A broad array of social and economic changes is necessary to overcome the poverty, lack of education, and limited control over their own lives that often keep women's hopes from coming true. But women can take an important step forward when they make their own reproductive choices--about marriage, sex, childbearing, and contraception. PMID- 7991716 TI - [Mikolajus Konstantinas Ciurlonis, visionary artist]. AB - The author presents a very interesting account of the personality of M. K. Ciurlonis (1875-1911). He was regarded as a precursor of abstractionism and surrealism--"The poet of music and painting". Thousands of his music al compositions and pictures gave him a place among the very best of artists of Eastern Europe of his epoch. He used to say that the influence of music was shown in his paintings and the influence of paintings in his musical compositions. His own philosophy of art has been expressed in his letters written to his brother and to his bride whom Ciurlonis married after 11 years of rather platonic friendship (one year before his death). He was born in to a Polish family living in Eastern Poland. His first music teacher was his father, an organ player. A medical doctor, friend of Prince Oginski facilitated the young man to attend the palace orchestra and after that the prince who was also a musical composer and a lover of art, helped Ciurlonis to study music in the best schools in Warsaw and Leipzig. Since his childhood Ciurlonis loved to draw and to paint. After having finished his music study he spent some months studying in the Academy of Fine Arts and after that he sacrificed himself to both arts. Influenced by his bride he considered himself to be Lithuanian and worked very hard for the liberation of Lithuania. (ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7991718 TI - A multidimensional approach to analysis of cerebrospinal fluid biogenic amines in schizophrenia: I. Comparisons with healthy control subjects and neuroleptic treated/unmedicated pairs analyses. AB - Recent hypotheses and findings indicate that measurements of interactions between cerebrospinal fluid (CSF) biogenic amine systems, rather than measurement of CSF biogenic amine metabolites, better correlate with clinically important findings in schizophrenia. To test hypotheses, we used a recent technological advance in high performance liquid chromatography with electrochemical detection and combined it with multivariate statistical analyses to study biogenic amine concentrations in CSF in schizophrenia. This approach enabled the study of the interactions of several metabolites of each of the three major neurotransmitter pathways (dopaminergic, noradrenergic, and serotonergic) to test existing hypotheses regarding the neurobiochemical basis of schizophrenia. Twenty biogenic amines, their metabolites, and other compounds from 24 medication-free schizophrenic patients and 12 normal control subjects were simultaneously measured using a recently developed technique of gradient high performance liquid chromatography coupled with a 16-channel electrochemical array detector. After covariation for storage time, results of a stepwise discriminant function analysis comparing the control and patient groups identified tryptophan, tryptophol, and epinephrine as discriminating variables. Hotelling's paired T2 test from a subgroup of schizophrenic patients studied while they were and were not receiving neuroleptic treatment did not yield any significant differences between subgroups. A discussion of the findings and a comparison with previous studies of CSF biogenic amines in schizophrenia are presented. PMID- 7991719 TI - A multidimensional approach to analysis of cerebrospinal fluid biogenic amines in schizophrenia: II. Correlations with psychopathology. AB - As part of a multidimensional study of cerebrospinal fluid biogenic amine metabolites in schizophrenia, the relationship between neurochemical measures and psychopathology assessed using the Psychiatric Symptom Assessment Scale (PSAS) was analyzed. In a group of 20 unmedicated patients, 3,4-dihydroxyphenylacetic acid (DOPAC) was a predictor of symptom severity in a stepwise multiple regression model. Values of 3-hydroxykynurenine and metanephrine in the unmedicated state predicted clinical response in a stepwise multiple regression model, as measured by improvement in PSAS mean item score following 6 weeks on a standard dose of neuroleptic. In a subgroup of 14 patients in whom both off- and on-medication concentrations of cerebrospinal fluid biogenic amines and metabolites were measured, change in 3-hydroxykynurenine predicted clinical outcome in a multiple regression model. These findings point toward the need to examine the role of the kynurenine pathway of tryptophan metabolism in the pathophysiology of schizophrenia. PMID- 7991720 TI - Neuropsychological prognosis and clinical recovery. AB - This report examines prognostic implications of neuropsychological deficit for clinical symptomatic improvement. Neuropsychological performance levels are related to the Brief Psychiatric Rating Scale thinking disturbance, paranoid disturbance, withdrawal/retardation, and anxiety/depression scales at hospital admission and discharge in 68 schizophrenic and psychotic and nonpsychotic mood disorder patients. Findings indicate a relationship between neurocognitive deficit and thinking disturbance at admission; however, neuropsychological impairment predicts blunted affect/emotional withdrawal at discharge, after the acute psychopathology resolves. Neuropsychological deficit is nonspecific, occurring across a broad range of cognitive-perceptual functions. These data suggest that neuropsychological dysfunction may be prognostic of a more chronic residual disorder in both schizophrenia and major psychotic and nonpsychotic mood disorder syndromes. PMID- 7991721 TI - Day-night variations in melatonin secretion by the pineal gland during febrile and epileptic convulsions in children. AB - The pineal gland is a complex neuroendocrine organ with pronounced effects on central nervous system activity. Because previous studies in animals and humans have suggested an anticonvulsant role for the pineal hormone melatonin, we studied the day-night variations in plasma melatonin in normal children and children with febrile or epileptic convulsions. We found significant changes in day-night melatonin levels during convulsions, consistent with the hypothesis that melatonin has an inhibitory function on central nervous system activity. PMID- 7991722 TI - In vivo serotonin release and learned helplessness. AB - Learned helplessness, a behavioral depression caused by exposure to inescapable stress, is considered to be an animal model of human depressive disorder. Like human depression, learned helplessness has been associated with a defect in serotonergic function, but the nature of this relationship is not entirely clear. We have used in vivo microdialysis brain perfusion to measure serotonin (5 hydroxytryptamine, 5HT) in extracellular space of medial frontal cortex in conscious, freely moving rats. Basal 5HT levels in rats perfused before exposure to tail-shock stress did not themselves correlate with subsequent learned helplessness behavior. However, 5HT release after stress showed a significant increase with helpless behavior. These data support the hypothesis that a cortical serotonergic excess is causally related to the development of learned helplessness. PMID- 7991723 TI - Five-component model of schizophrenia: assessing the factorial invariance of the positive and negative syndrome scale. AB - A five-component model of schizophrenia has been presented by Kay and Sevy based upon an analysis of the Positive and Negative Syndrome Scale. Kay and Sevy found factorial validity for negative and positive syndromes, and they identified excitement, depressive, and cognitive components as well. They suggested that subtypes and syndromes can be mapped along dimensions presented in their model. The present study compares the five-component solution for a new sample of 146 subjects to a reanalysis of the Kay and Sevy data. Despite divergent demographic characteristics, the two samples produce similar dimensions. Correlations of component loadings and subject scores as well as confirmatory factor analysis are presented. Discussion focuses on points of agreement and important differences in the symptoms assigned to each component. How the dimensions relate to rationally derived models of positive and negative syndromes is reviewed, and implications for subtyping and other methods of examining the heterogeneity of schizophrenia are considered. PMID- 7991724 TI - Effect of the placebo control condition in neuroendocrine challenge studies. AB - Neuroendocrine challenge studies are frequently used to make inferences about the pathophysiology of psychiatric illness or about the effects of chronic psychotropic drug treatment on brain monoamine function. The outcome of these exploratory neuroendocrine tests, however, may be influenced by the effects of confounding variables, such as specific stress effects and variations in basal hormone levels. The inclusion of a placebo control condition minimizes the variability due to these variables. A number of recent neuroendocrine studies have omitted the placebo control condition. Based on experimental data, it can be shown that failure to include a placebo control condition may result in both Type I and Type II errors of inference. These results suggest a placebo control condition should be included in exploratory neuroendocrine challenge studies. PMID- 7991726 TI - Performance of nonpsychotic relatives of schizophrenic patients on cognitive tests. AB - We tested 54 nonpsychotic first degree relatives of 23 schizophrenic probands and 18 control subjects matched for age and education on several neuropsychological tests. The tests were selected to assess overall intellectual ability or because previous work indicated that they are particularly sensitive measures of cognitive dysfunction in schizophrenic patients. The relatives of schizophrenic patients performed significantly worse than the control subjects on tests of verbal fluency and on Trailmaking, part B. Each of these tests contributed unique variance to the discrimination between groups. The groups did not differ significantly on the number of perseverative errors on the Wisconsin Card Sorting Test, Wechsler Adult Intelligence Scale-Revised block design or vocabulary, or Trailmaking, part A. Eight relatives who met DSM-III-R criteria for schizotypal personality disorder were more impaired than the remaining 46 relatives on letter fluency, but otherwise their performance was similar to that of nonschizotypal relatives. These data suggest that close relatives of schizophrenic patients may have subtle neuropsychological impairments that are not necessarily associated with clinical symptoms of schizophrenia spectrum disorders. PMID- 7991725 TI - Latency to rapid eye movement sleep as a predictor of treatment response to fluoxetine and placebo in nonpsychotic depressed outpatients. AB - Fluoxetine and placebo were compared in 89 outpatients with major depression with (n = 45) or without (n = 44) a reduced or shortened rapid eye movement latency (SREML) (< or = 65 minutes) to determine whether rapid eye movement latency (REML) predicted placebo and/or antidepressant response. Men and women were stratified based on polysomnographic recordings and then randomly assigned to receive double-blind fluoxetine (20 mg/day) or placebo for 8 weeks after a 2 week, single-blind, placebo lead-in period. Fluoxetine-treated patients demonstrated a significantly greater reduction in the Hamilton Rating Scale for Depression total score and a significantly greater response rate than placebo treated patients in both the SREML and the combined strata. Treatment differences in the non-SREML stratum were not statistically significant. Results supported REML as a predictor of placebo nonresponse but did not predict a differential fluoxetine response in patients with SREML compared with patients without SREML. PMID- 7991727 TI - Decreased CSF inositol monophosphatase activity after lithium treatment. PMID- 7991728 TI - Sleep deprivation and thyroid hormones. PMID- 7991729 TI - Gender differences in a sample of adults with attention deficit hyperactivity disorder. AB - Although originally conceptualized as a childhood disorder, attention deficit hyperactivity disorder (ADHD) may also be an adult disorder. However, despite increasing media attention to adult ADHD, its validity has only recently been studied in a systematic fashion. The overrepresentation of females in adult samples in comparison to pediatric samples of ADHD raises additional questions about the validity of this disorder in adults. The goal of this article is to explore whether ADHD is a valid clinical entity in female subjects and whether it is expressed differently in male and female adults. To this end, we examined the clinical, cognitive, and functional characteristics of 128 referred adult ADHD cases of both sexes. Each subject had a clinical diagnosis of childhood-onset ADHD confirmed by structured interview. The male and female ADHD adults were similar to one another but more disturbed and impaired than non-ADHD adult control subjects. Compared with normal control females, ADHD women had higher rates of major depression, anxiety disorders, and conduct disorder; and more evidence of school failure and cognitive impairment. The consistency of these findings in both genders further supports the validity of the diagnosis of ADHD in adults. Our results stress the viability and importance of identification of female subjects with ADHD. The underidentification and undertreatment of females with ADHD may have substantial mental health and educational implications, suggesting that research is needed to develop a better understanding of clinical indicators of ADHD in females. PMID- 7991730 TI - Psychometric properties of the positive and negative syndrome scale (PANSS) in schizophrenia. AB - We analyzed the psychometric properties of the Positive and Negative Syndrome Scale (PANSS) in a sample of 100 DSM-III-R schizophrenic patients. Our findings coincided with the results of Kay's group in the following points: (1) the PANSS scores were normally distributed; (2) the positive and negative scales showed good interrater reliability; (3) positive and negative syndromes are independent constructs; (4) the positive and negative scales held a high concurrent validity in relation to the Scale for the Assessment of Positive Symptoms and the Scale for the Assessment of Negative Symptoms; and (5) although positive and negative syndromes showed factorial validity, they were not sufficient to account for the whole of the schizophrenic symptoms. Unlike Kay's group, we found a modest internal consistency of the positive scale, indicating that it is composed of several independent components. The data suggest that the distinction between positive and negative symptoms is an oversimplification, and that schizophrenic symptoms can be better conceptualized as composed of, at least three dimensional syndromes: positive, disorganized, and negative. PMID- 7991731 TI - A reconsideration of the relationship between cerebral structural abnormalities and family history of schizophrenia. AB - In a study of 229 schizophrenic patients for whom reliable family history information was available, ventricular size and incidence of ventricular enlargement were found to be greater in male cases without a family history of schizophrenia. A significant sex by family history interaction on cerebral ventricular dimension was detected. The age-corrected morbid risk for schizophrenia was lower among first degree relatives of male probands with ventricular enlargement vs. those with normal ventricles, but similar in relatives of females with and without ventricular enlargement. On the other hand, no association was found between family history and degree of cortical atrophy. A meta-analysis of published studies on the issue revealed 20% larger ventricles in patients without any known genetic predisposition for schizophrenia. PMID- 7991732 TI - Regional cerebral blood flow distribution in newly diagnosed schizophrenia and schizophreniform disorder. AB - Regional cerebral blood flow distribution (rCBF) in 24 first admissions with schizophrenia or schizophreniform disorder and in 17 healthy volunteers was examined. Single photon emission computed tomography with a brain-retained tracer, technetium-99m-d,l-hexamethyl-propylene amine oxime, was used to study subjects under resting conditions and during performance of the Wisconsin Card Sorting Test. The study is a replication of a previous investigation in an independent series of patients and healthy volunteers. The patients had significantly lower relative blood flow in prefrontal regions during activation than did the healthy volunteers. An earlier series of 19 patients and 7 healthy volunteers was studied using exactly the same procedure. Analyses of the combined samples from the two studies (43 patients and 24 healthy volunteers) showed the patients to have significantly lower relative flow in prefrontal regions both at rest and during activation and higher flow in the left striatum during activation. The same finding emerged when analyses were confined to drug-naive patients and patients educationally matched to the healthy volunteers. The study suggests a defective frontostriatal interrelationship in schizophrenia and schizophreniform disorder. PMID- 7991733 TI - Absence of linkage between schizophrenia and the dopamine D4 receptor gene. AB - The dopamine D4 receptor gene and the closely placed tyrosine hydroxylase (TH) receptor gene are important candidate genes for schizophrenia; both are located on the short arm of chromosome 11. Multipoint linkage analyses excluded linkage of schizophrenia/schizoaffective disorder to both candidate genes in a sample of 15 multiplex and systematically recruited families. This result was not dependent on the definition of the affection status and on the specification of the mode of transmission (insofar as it is monogenic) of the disease. There was no evidence for a subgroup of families being linked. This result does not preclude the possibility that the D4 receptor gene or the TH gene has only a nonmajor effect on the genetic etiology of schizophrenia or that families in other populations are linked. PMID- 7991734 TI - Decreased adhesiveness and altered cellular distribution of fibronectin in fibroblasts from schizophrenic patients. AB - Relative to those from normal subjects, cultured skin fibroblasts from schizophrenic patients have been found to show abnormal growth characteristics and morphology. This study compared skin fibroblasts from 10 drug-free schizophrenic patients and 10 normal control subjects on cell adhesiveness to the substratum. Relative to fibroblasts from normal controls, those from patients showed significantly decreased cell adhesiveness, with no overlap in distribution between the groups. Since fibronectin, a major cell surface molecule, is known to be involved in the fibroblast adhesion to substratum, its extracellular and intracellular distribution was determined by immunocytochemical analysis. Both extracellular and intracellular levels of fibronectin were significantly lower, and the distribution was altered in fibroblasts from the patients. PMID- 7991735 TI - Platelet serotonin measures in posttraumatic stress disorder. PMID- 7991736 TI - Levels of explanation--symptoms, neuropsychological deficit and morphological abnormalities in schizophrenia. PMID- 7991738 TI - Central monitoring deficiency and schizophrenic symptoms. AB - Twenty-five schizophrenic patients currently experiencing Schneiderian symptoms performed a series of tasks in which drawings had to be made in the absence of immediate visual feedback. In comparison to 10 normal controls and to 30 patients not experiencing Schneiderian symptoms, the target group had great difficulty in keeping track of their performance and remembering what actions they had made. These results are consistent with the hypothesis that Schneiderian symptoms (such as delusions of alien control) are associated with impairments in the central monitoring of action. PMID- 7991737 TI - Neuroendocrine and clinical effects of electroconvulsive therapy and their relationship to treatment outcome. AB - Two groups of variables, endocrine and clinical, have been reported to have predictive value in determining response to electroconvulsive therapy (ECT) in depressed patients. Baseline levels of oxytocin associated neurophysin (OAN) and peak OAN response to ECT may predict clinical outcome, while the presence of delusional symptoms may indicate favourable initial response to ECT. The purpose of this study was to examine the relationship between these variables on initial and longer term response over a course of ECT, using a direct measure of plasma oxytocin concentrations. A substantial and immediate increase in oxytocin was seen after the first ECT, with significantly attenuated responses after the third and fifth ECTs. Increased plasma vasopressin concentrations were seen after all ECT treatments, each response being of similar magnitude. No associations were found between either endocrine baseline levels or peak responses, and clinical outcome. Only clinical variables predicted outcome, as patients with psychotic symptoms had more rapid initial response to ECT, and patients who had relapsed 2 months after the end of ECT had significantly higher depression ratings at day 14 of treatment than treatment responders. PMID- 7991739 TI - An overview of family interventions and relapse on schizophrenia: meta-analysis of research findings. AB - The purpose of this overview is to appraise the studies on the efficacy and effectiveness of family interventions in decreasing relapse in schizophrenic patients. The studies were identified by means of a computerized MEDLINE search, and the scanning of review articles and the reference lists of the primary articles identified. More than 300 citations were reviewed, and the potentially relevant articles revealed six randomized controlled trials that were included in this meta-analysis. The criteria for selecting potential studies as well as for the meta-analysis were tested by means of an inter-rater reliability check that showed a good agreement between two independent raters (kappa = 0.83, and kappa = 0.82, respectively). There were independent assessments of the quality of the studies selected, and data extraction comprised a descriptive information of the study population, the types of interventions, and the relevant outcome measurements. The total number of patients included in the six trials was 350 (181 in the control group and 169 in the experimental group). Regarding the decrease of relapse in the experimental group, the pooled odds ratios and their 95% confidence intervals were: 0.30 (0.06, 0.71) for six months; 0.22 (0.09, 0.37) for nine months; and 0.17 (0.10, 0.35) for the 2-year follow-up. Two to five patients needed to be treated to avert one episode of relapse in a nine month follow-up. The changes in Expressed Emotion status between experimental and control group combining nine months and one year follow-ups were shown to be marginally significant (P < 0.06), in favour of the experimental group. Emotional over-involvement was also marginally significant (P < 0.07), and there was no statistical difference in the distribution of criticism and hostility. In addition, the experimental group showed a significant increase with drug compliance and a reduction in hospitalization over time. These findings are discussed in light of the potential ingredients in the efficacy of family interventions by focusing on the limitations of using relapse as primary outcome in the assessment of efficacy trials with schizophrenic patients. PMID- 7991740 TI - Parental treatment and the equal environment assumption in twin studies of psychiatric illness. AB - The validity of the twin method depends on the equal environment assumption (EEA) -that monozygotic (MZ) and dizygotic (DZ) twins are equally correlated in their exposure to environmental factors of aetiological importance for the trait under study. Parents may treat MZ twins more similarly than DZ twins thereby potentially violating the EEA. We tested this hypothesis for four common psychiatric disorders (major depression, generalized anxiety disorder, phobia, and alcoholism) in a population-based sample of female-female twin pairs where analyses indicate sufficient statistical power meaningfully to test the EEA. Mother's and father's beliefs about their twins' zygosity disagreed with assigned zygosity in approximately 20% of cases, often because of what they were told about their twins' zygosity at their birth. By structural equation model-fitting, we found no evidence that mother's or father's perceived zygosity influenced twin resemblance for any of the disorders. Compared to parents of DZ twins, parents of MZ twins were more likely to report that, in rearing their twins, they emphasized their similarities more than their differences. However, by model-fitting, mothers' and fathers' approach to raising twins had no significant influence on twin resemblance for the four examined psychiatric disorders. These results suggest that the differential treatment of MZ and DZ twins by their parents is unlikely to represent a significant bias in twin studies of these major psychiatric disorders. PMID- 7991741 TI - Course of multi-impulsive bulimia. AB - Thirty-two consecutively admitted females with bulimia nervosa (purging type) according to DSM-IV and additional impulsive behaviours (multi-impulsive bulimia (MIB)) and 32 age-matched female controls with DSM-IV bulimia nervosa (purging type) (uni-impulsive bulimia (UIB)) were assessed longitudinally on admission and at discharge following in-patient therapy and at a 2-year follow-up. Multi impulsive bulimics were defined as presenting at least three of the six of the following impulsive behaviours in their life-time in addition to their bulimic symptoms at admission: (a) suicidal attempts, (b) severe autoaggression, (c) shop lifting (other than food), (d) alcohol abuse, (e) drug abuse, or (f) sexual promiscuity. Multi-impulsive bulimics were more frequently separated or divorced, had less schooling and held less-skilled jobs. Except for interoceptive awareness (EDI), which was more disturbed in multi-impulsive bulimics, there were no differences concerning scales measuring eating disturbances and related areas. Multi-impulsive bulimics showed more general psychopathology--anxiety, depression, anger and hostility, psychoticism--differed in several personality scales from uni-impulsive bulimics (e.g. increased excitability and anger/hostility) and had overall a less favourable course of illness. Multi impulsive bulimics also received more in- and out-patient therapy previous to the index treatment and during the follow-up period. The data support the notion that 'multi-impulsive bulimia' or 'multi-impulsive disorder' should be classified as a distinct diagnostic group on axis I or that an 'Impulsive Personality Disorder' should be introduced on axis II. The development of more effective treatment for multi-impulsive bulimia is warranted. PMID- 7991742 TI - Bulimia comorbidity in the general population and in the clinic. AB - This study compares rates of comorbidity of lifetime psychiatric disorder in a clinical sample of women with bulimia, with general population base rates, and with rates of comorbidity among bulimic women in the general population. Eighty four per cent of the clinical sample of bulimic women had a lifetime affective disorder, and 44% a lifetime alcohol or drug disorder. These rates of disorder were significantly higher than the base rates in the general population. Bulimic women in the general population also had more affective and substance-use disorders than the general population base rates, but the rates of these disorders were lower than found in the clinical sample. In the general population, quite similar rates of other disorders including generalized anxiety, panic, phobia and obsessive-compulsive disorder, are found among those with bulimia, substance-use disorder and depression. Furthermore, among those with depression and substance-use disorder in the general population, rates of eating disorder are comparable. Rather than suggesting a specific relationship between bulimia and either depression or substance-use disorder, the data from this study suggest that the presence of any disorder is associated with a non-specific increase in the likelihood of other psychiatric disorder. PMID- 7991743 TI - A prospective study of widowhood and changes in symptoms of depression in a community sample of the elderly. AB - This survey examines changes in depressive symptomatology (CES-D) during bereavement in 1046 elderly subjects, of whom 139 became widowed during follow up. Depression scores increased during the first year of bereavement, but generally returned to pre-widowhood levels thereafter. However, depression scores remained elevated among young-old widows (65-74-year-olds) well after the first year of widowhood. Using cut-off scores, rates of high depressive symptoms remained somewhat elevated over baseline levels. Increases in depression scores during bereavement were not explained by socio-economic variables, health habits and health status. It is concluded that particularly young-old widows are at risk of developing chronic depressive symptomatology during bereavement that may warrant clinical attention. PMID- 7991744 TI - The psychological impact of motor neurone disease. AB - Self-report measures were completed by 59 individuals with motor neurone disease (MND) in order to assess whether: (a) MND affects patients' psychological well being and quality of life; (b) if greater affective disorder is associated with greater physical disability; (c) whether accepting the illness and ways of coping have an impact on psychological distress, and (d) if beliefs over control of their health shift as the disease progresses. Results indicated that the effects of MND on everyday functioning accounted for incidence of depression and low self esteem. Acceptance of illness was related to severity of symptoms and was a significant factor irrespective of level of physical symptomatology. Ways of coping with the illness did not relate in any significant way to severity of symptoms. Mild physical impairments were associated with an 'internal' view of control over health. PMID- 7991745 TI - The differentiation of depression from dementia by temporal lobe magnetic resonance imaging. AB - Temporal lobe Magnetic Resonance Imaging (MRI) was performed in 43 patients with NINCDS/ADRDA Alzheimer's disease (AD) (33 probable, 7 possible, 3 definite) and 32 subjects with DSM-III-R Major Depression (DEP) matched for age, sex and level of education. Hippocampus (anterior and posterior, right and left), amygdala, entorhinal cortex, parahippocampal gyrus and cerebral cortex were rated for atrophy on a 4-point scale. Good discrimination between groups could be achieved using a cut-off of 2 or more on anterior hippocampal atrophy rating (sensitivity 93%; specificity 84%; 89% cases correctly grouped overall). Even among a subgroup of 9 mild AD subjects and 10 cognitively impaired DEP subjects (matched on mini mental state score), the same cut-off correctly grouped 84% (16/19) cases. Hippocampal atrophy increased with age in both AD and DEP subjects leading to a reduction in specificity (but not sensitivity) for those aged over 75. Within the AD group a significant correlation was observed between length of history and atrophy of the entorhinal cortex (r = 0.39, P = 0.009). We conclude that temporal lobe atrophy on MRI can provide good discrimination between AD and DEP subjects, including those DEP patients with cognitive impairment apparent on screening tests of cognitive function. PMID- 7991746 TI - Pathways to psychiatric care in south-Verona, Italy. AB - This paper compares the pathway to psychiatric care of patients contacting the South-Verona Community Psychiatrics Service (CPS) with the pathways described in other countries, using the method of the WHO cross-cultural study of pathways in psychiatric care. One hundred and sixteen South-Verona residents starting new episodes of care were traced and included in the study. The first port of call for 92% of patients was a doctor. More than one-third arrived at the CPS directly, not filtered by other carers. One-third went first to the GP and then straight to the CPS. Both the median total interval since onset of symptoms and the median interval between onset of the problem and first seeking care was 8 weeks. Patients presenting first at the two major ports of call tend to have a quite similar latency period before seeking care. Problems presented are represented mostly by depression and anxiety. The diagnosis of affective disorders occurred in more than half of the sample, followed by neurotic and somatoform disorders and schizophrenia and related disorders. The intervals after seeing the first carer are short and quite homogeneous among all patients. More than three-quarters of the patients said that they received some form of treatment for their presenting problems prior to arrival at the CPS, mostly psychopharmacotherapy with sedatives/hypnotics. These results are discussed in the light of those obtained in the WHO cross-cultural study. PMID- 7991747 TI - The effect of social adversity on the fatigue syndrome, psychiatric disorders and physical recovery, following glandular fever. AB - Two hundred and fifty patients attending primary care with glandular fever or an upper respiratory tract infection were studied prospectively up to 6 months after onset. Of these patients 228 were interviewed with the Life Events and Difficulties Schedule and the Schedule for Affective Disorders and Schzophrenia, giving Research Diagnostic Criteria for psychiatric disorders. The experience of severe social adversity (provoking agents) had a significant association with psychiatric disorder at 2 months (odds ratio = 5.3) and 6 months (odds ratio = 5.8) after onset of infection. This association was especially significant for depressive illness (odds ratio = 9.1 at 2 months and 11.9 at 6 months). In contrast, social adversity had little association with the development of the post-infectious fatigue syndrome, or delayed physical recovery. Social adversity may be an important maintaining factor for psychiatric disorders, especially depressive illness, following acute infections. PMID- 7991748 TI - Psychosocial factors and chronic fatigue syndrome. AB - This study investigated the number and severity of life events, Type A behaviour, coping strategies and social support differences between chronic fatigue and irritable bowel syndrome patients prior to illness and between these groups and healthy controls. Although few differences were found between the groups for life events, a number of interesting results emerged with regard to different aspects of Type A behaviour, various coping strategies and social support. These findings are discussed with respect to existing research in the field. PMID- 7991749 TI - Visual and motor functions in graphically gifted savants. AB - Savant artists represent a conundrum to our understanding of the nature of high level specific talents as well as to the concept of general intellectual impairment. In the present paper, we are particularly concerned with the relationship between general perceptual-motor functions in relation to drawing aptitude. Drawing is by definition a perceptual-motor operation, yet mental handicap tends to be associated with some degree of impairment in this area. The following study seeks to isolate such aspects of performance on general perceptual-motor skills that might be associated with drawing ability, and may thus be regarded as building blocks underlying the manifestation of graphic talent. The results are discussed in terms of the relationships between graphic talent, non-verbal intelligence and visual-motor functions. PMID- 7991750 TI - Correlates of codisorders in homeless and never homeless indigent schizophrenic men. AB - We recently completed a case-control study of 100 literally homeless and 100 never homeless indigent schizophrenic men in New York City, in which concurrent substance abuse and antisocial personality disorder were widespread. In this paper we probe the correlates of 'pure' schizophrenia (single disorder, N = 60), schizophrenia and substance abuse (double disorder, N = 89), and schizophrenia, substance abuse, and antisocial personality disorder (triple disorder, N = 50), across the homeless/never homeless distinction. Subjects were recruited from a homeless shelter and mental health service programmes in Upper Manhattan. Psychologist and social worker interviewers administered the Structured Clinical Interview for DSM-III-R, I, and II and other structured instruments to explore social, family and illness history, the current illness, and aspects of treatment and family support. Codisorder subjects emerged from more disadvantaged family backgrounds, experienced greater school difficulties, began drug use in early adolescence, were more prone to hyperactivity in childhood, and were more likely to have spent time in jail. While codisorder groups did not differ on key aspects of schizophrenia, the triple disorder group was found to suffer from a more severe form of substance abuse than double disorder subjects, associated with an earlier age of onset and abuse of a wider array of substances. The widespread prevalence of codisorders among indigent schizophrenic men has major significance for clinical psychiatry. Study of the correlates of codisorders has revealed important differences in social, family, and illness history which may guide the development of more effective treatments and improved service delivery. PMID- 7991751 TI - Volumetric MRI measurements in bipolars compared with schizophrenics and healthy controls. AB - Twenty-six patients with RDC bipolar disorder were compared with a previously reported group of 48 RDC schizophrenics and 34 healthy controls, using volumetric MRI measurements of cerebral, cortical and sulcal volumes. The bipolar group appeared no different from the controls, and both of these groups had significantly larger cerebral and cortical volumes than the schizophrenics. Our previous report of a significantly reduced cortical volume in the schizophrenic group, with a corresponding increase in the volume of sulcal fluid is, therefore, not a generalized feature of psychotic illness but may be more specific to schizophrenia. PMID- 7991752 TI - Development and validation of the computerized clinician administered post traumatic stress disorder scale-1-revised. AB - A computer administered version of the clinician administered post-traumatic stress disorder (PTSD) scale-1 was developed to assess PTSD in subjects presenting with psychological symptoms following exposure to a traumatic event. Both forms were administered to 40 subjects who met the Diagnostic and Statistical Manual, third edition, revised (DSM-III-R) criteria for exposure to a significantly traumatic stressor. Inter-observer reliability was demonstrated with a kappa statistic of 0.90. The computer version had a sensitivity of 0.95 and a specificity 0.95. A correlation of 0.95 was found between the two versions and the mean score difference was non-significant. The computer form demonstrated adequate internal reliability and test-retest reliability. Overall results suggest the computer version is a valid and reliable measure of PTSD. PMID- 7991753 TI - The predictive utility of expressed emotion in schizophrenia: an aggregate analysis. AB - We analysed aggregate data from 25 studies linking Expressed Emotion (EE) and schizophrenia. We had access to original data sets from 17 studies, and used published data from the remainder. This provided us with 1346 cases from around the world. The association of EE with relapse was overwhelming, and was maintained whatever the geographical location. The predictive capacity of EE was virtually identical in men and women. While high contact with a high EE relative increased the risk of relapse, the opposite was true in low EE households. Medication and EE were independently related to relapse, and thus EE status has no bearing on the decision to prescribe. Our findings were confirmed using log linear analysis. PMID- 7991754 TI - Anorexia nervosa: change over time in age of onset, presentation and duration of illness. AB - The question as to whether anorexia nervosa as an illness has transformed itself was partially addressed in an investigation into the possible change over time in age of onset, age of presentation and the derived variable, delay between onset and presentation. These three variables were examined in 827 patients diagnosed as suffering with anorexia nervosa, who had attended the Eating Disorders Unit at the Middlesex and St George's Hospitals from 1960 to 1990. This analysis revealed a stable age of onset but a lengthening in duration of illness and associated increase of age at presentation. However, investigation of data obtained from two other tertiary referral centres revealed stability of all three variables over time. The overall conclusion was that there has been no change in the age of onset of anorexia nervosa during the past 30 years. The increasing delay in presentation to the eating disorders clinic is most likely attributable to a change in the practice of patient referrals to a national tertiary referral centre. PMID- 7991755 TI - The effect of personality disorder on clinical outcome, social networks and adjustment: a controlled clinical trial of psychiatric emergencies. AB - One hundred psychiatric emergencies presenting to an inner London teaching hospital had formal assessments of psychopathology, personality disorder (using both ICD-10 and the Personality Assessment Schedule), social networks and social functioning before being randomly assigned to a multidisciplinary community-based team (Early Intervention Service (N = 48) or conventional hospital-based psychiatric services (N = 52) and treated for a period of 12 weeks. The ICD-10 classification yielded a higher proportion (50%) of personality disordered patients than the Personality Assessment Schedule (34%) and those from ethnic minorities (mainly Afro-Caribbean) and upper social classes had a lower incidence of personality disorder. Social networks were smaller in personality disordered patients and there were fewer attachment figures. Improvement in social function, and to a lesser extent with depressive symptomatology, was better in patients with no differences were found between the numbers and duration of social contacts in the two services and it is concluded that the better outcome in the community-treated patients was independent of changes in social networks. PMID- 7991756 TI - An investigation of the adequacy of MEDLINE searches for randomized controlled trials (RCTs) of the effects of mental health care. AB - Valid reviews of the effects of mental health care depend on identifying as high a proportion as possible of relevant randomized controlled trials (RCTs). To investigate the sensitivity and precision both of MEDLINE and of hand-searching for RCTs in mental health, 12 journals specializing in mental health and indexed by the National Library of Medicine (NLM) for MEDLINE were searched for the years 1971, 1976, 1981, 1986 and 1991. The sensitivity of the hand-search was 94% (95% Confidence Interval (CI) 93-95%), but it had a precision of only 7% (CI 6-8%). The optimal MEDLINE search had a sensitivity of only 52% (CI 48-56%) and a precision of 59% (CI 55-63%). Of the reports of RCTs identified by the hand search, 9% (CI 7-11%) were not included in MEDLINE at all. Authors had included methodological descriptions in 84% (CI 80-88%) of RCTs found by the hand-search but missed by the MEDLINE search. Systematic reviews of mental health care which are based solely on MEDLINE searches of the literature will miss a large proportion of the relevant RCTs, and are thus liable to random error and bias. A register of mental health RCTs is urgently required. PMID- 7991757 TI - Self-monitoring in speech production: effects of verbal hallucinations and negative symptoms. AB - This paper reports results of a study on self-monitoring in speech production. Thirty schizophrenics, varying in verbal hallucination and in negative symptoms status, and 17 controls were tested on the reporter test. The position of interruptions of the speech-flow to repair errors was used to indicate whether the detection of the errors was through monitoring of internal phonetic plans or through external acoustic feedback. We have found that the internal error detection was twice as frequent in controls as in schizophrenics. The relevance of this finding to Frith's (1992) model of schizophrenia is discussed. Our conclusion is that the problem with internal monitoring of phonetic plans is common to all schizophrenics, and not just to those with verbal hallucinations. PMID- 7991759 TI - Fractal analysis of the boundary between white matter and cerebral cortex in magnetic resonance images: a controlled study of schizophrenic and manic depressive patients. AB - This paper reports development of a computerized ('box-counting') method for estimation of fractal dimension (FD) of the magnetic resonance image (MRI) boundary between cerebral cortex and white matter; and the application of this method to MRIs of 39 schizophrenics (SZs), 23 manic-depressives (MDs) and 31 controls (CONs). Mean FD across all diagnostic groups was 1.402; 95% confidence interval (CI) 1.399 to 1.406. Mean FD was greater in boundaries extracted from manic-depressive patients than in boundaries extracted from controls (difference between MD and CON mean FDs = 0.008; 95% CI -0.002 to +0.018); and less in schizophrenics than in controls (difference between SZ and CON mean FDs = -0.003; 95% CI -0.011 to +0.005). Mean FD was positively correlated with subcortical volume and anterior cerebral volume, and negatively correlated with sulcal cerebrospinal fluid volume. Significant differences in mean FD between diagnostic groups were demonstrated by analysis of covariance (ANCOVA; P < 0.01), with age and volumetric measures of brain size as covariates; and manic-depressive boundaries were shown to have significantly greater values for residual FD (after controlling for effects of brain size) than boundaries extracted from controls (t test; P < 0.05). It is proposed that FD is a useful measure of clinically relevant differences in the complexity of MRI boundaries. PMID- 7991758 TI - Assessing cognitive abilities and dementia in a predominantly illiterate population of older individuals in Kinmen. AB - A community survey of dementia was conducted on a Chinese islet. A total of 221 men and 234 women in the age range of 50-92 were assessed. The Cognitive Abilities Screening Instrument (CASI), a 100-point cognitive test designed for cross-cultural studies and adapted in Chinese for individuals with little or no formal education, was administered twice by trained field workers with a retest interval of 3 to 4 weeks. In addition, all participants were assessed by physicians who did not know the CASI scores. The physicians' assessment included a complete neurological examination, plus semi-structured tests and interviews covering cognitive abilities, daily activities, depression, cerebrovascular disease, and Parkinson's disease. Dementia was diagnosed by consensus among the physicians according to the DSM-III-R criteria. Among the 455 participants, 16 cases of dementia were identified, including 13 with probable Alzheimer's disease and 1 each with vascular dementia, Parkinson's disease, and alcoholism. The rates of dementia were 0, 3.9 and 11.5% for the age groups of 50-69, 70-79 and 80-92; and 4.4, 2.0 and 0% for the education groups of 0-1, 2-6 and 7-15 years of schooling. No sex difference was found after controlling for education. The Chinese version of the CASI had an intraclass retest reliability of 0.90. Using a cut-off score of < or = 50 for dementia, the sensitivity was 0.88 and the specificity was 0.94. The preliminary study suggests that the CASI can be used in Chinese populations with generally low education levels and that Alzheimer's disease was the most common type of dementia in this population. PMID- 7991760 TI - Personality characteristics of the parents of autistic individuals. AB - Personality characteristics of 87 parents of autistic probands and 38 parents of Down's syndrome probands were examined using a standardized personality interview. Using best-estimate ratings derived from subject and informant interviews, parents of autistic individuals were rated significantly higher than controls on three characteristics: aloof, untactful and undemonstrative. When ratings were based on interviews with subjects only, parents of autistic probands were rated as significantly more aloof, untactful and unresponsive. There were no significant differences between parent groups on ratings based on informant interviews only. The implications of these findings for future family studies of autism are discussed. PMID- 7991761 TI - The role of central oxytocin in obsessive compulsive disorder and related normal behavior. AB - Oxytocin (OT) is a neurosecretory nonapeptide synthesized in hypothalamic cells, which project to widely distributed sites in the CNS as well as the neurohypophysis. Central OT affects a variety of cognitive, grooming, affiliative, sexual, and reproductive behaviors in animals. Obsessive Compulsive Disorder (OCD) includes a range of cognitive and behavioral symptoms that bear some relationship to dimensions of behavior associated with OT. Anecdotal data and a recently completed cerebrospinal fluid (CSF) study provide evidence that some forms of OCD are related to OT dysfunction. Based on these findings, we hypothesize: 1) that some forms of OCD are at the extreme end of a range of normal behaviors that are mediated by OT and related systems; and that 2) some normal cognitive, affiliative, and sexual behaviors contain elements that are similar to features of OCD. Alternative hypotheses are considered, and a series of predictions are presented concerning the relationship between central OT and the onset, course, treatment response, and response to challenge procedures seen in this form of OCD. PMID- 7991762 TI - Research perspectives in psychoneuroimmunology IV, 1993. PMID- 7991763 TI - Plasma cortisol levels and reactivation of latent Epstein-Barr virus in response to examination stress. AB - In this study, we explored the possibility that glucocorticoid hormones, known to increase under stress, might be one component of the mechanism involved in induction of latent Epstein Barr virus (EBV). We obtained blood samples from 45 male medical students during examinations and approximately 3-4 weeks before the examinations (baseline) and measured antibody titers to EBV and plasma cortisol levels. We found reproducible changes in EBV, virus capsid antigen (VCA) antibody titers, with higher antibody titers observed in the examination blood samples consistent with the reactivation of latent virus. However, we found no evidence that day and night plasma cortisol values across the sampling points changed significantly from baseline to examinations. Therefore, academic stress did not elevate cortisol levels, but increases in EBV VCA antibody titers were still observed. The data suggest in these subjects that other neuropeptides or hormones were involved in the induction of latent EBV. PMID- 7991764 TI - Regional thyroid hormone levels in rat brain. AB - Levels of T4 and T3 were measured in half-brain and seven brain regions. Although thyroid hormones were distributed throughout the brain, T4 levels were highest in cerebellum and thalamus. The highest T3 levels were observed in the thalamus and lowest levels were found in olfactory bulb, hypothalamus, and amygdala. PMID- 7991765 TI - Failure of periodontal treatment. AB - Treatment failures appear to occur more frequently in periodontology than in other dental disciplines. Inappropriate patient selection, incomplete diagnostic procedures, errors in diagnosis or prognosis, treatment difficulties, unsupervised healing, and the absence of maintenance therapy may be causes of such failures. A regular recall program can largely prevent such failures. PMID- 7991766 TI - Resin-bonded ceramic onlays for retained primary molars with infraocclusion. AB - In some patients, primary molars with no permanent successor can be retained for an indefinite time; however, if occlusal relationships necessitate intraocclusal augmentation, cast ceramic onlays can provide an excellent solution. This paper reports the case of a teenager in whom two cast ceramic onlays were bonded with resin to retained mandibular primary molars, to create an esthetic and functional occlusion. PMID- 7991767 TI - Provisional treatment for resin-bonded fixed partial dentures. AB - The resin-bonded fixed partial denture is a conservative option for the replacement of a missing tooth. It has a good prognosis and offers several advantages over a conventional fixed partial denture. However, it does not allow for placement of a provisional fixed partial denture. In some situations, it is important to provide some type of interim treatment. This can be accomplished by several techniques, that include placement of either a removable or bonded replacement tooth. The provisional treatment can provide an esthetic solution and maintain tooth position while the fixed partial denture is being made by the dental laboratory. PMID- 7991768 TI - The construction of crowns for removable partial denture abutment teeth. AB - The construction of crowns for teeth that will serve as abutment teeth for removable partial dentures is an important and technically demanding procedure. The preparation of the tooth itself must include provision for the components and path of placement of the removable partial denture and at the same time conform to all the parameters associated with proper tooth preparation. Some of the factors unique to surveyed crowns that must be considered include the position of the tooth in relation to the proposed occlusal plane with the removable partial denture, the type of facial and lingual tooth contours desired for the direct retainer, the size and suitability of existing restorations, and the proposed path of placement and removal of the removable partial denture relative to the orientation of the abutment tooth as well as to other adjacent teeth if the abutment also is to be used as a fixed partial denture retainer. The design requirements for the removable partial denture must be determined before treatment is initiated, to account for all of these factors. PMID- 7991769 TI - Pulpal response after complete crown preparation, dentinal sealing, and provisional restoration. AB - This study evaluated the acute pulpal healing response following preparation, etching, and sealing of the prepared vital dentin with a 4-methacryloxyethyl trimellitate anhydride (4-META) bonding system. Adult monkey teeth received crown preparations with chamfer margins, prepared with a diamond used at ultra high speed with water cooling. Vital dentin was etched with 10% citric acid-3% ferric chloride, rinsed, and sealed with 4-META system. A provisional crown was formed with a low-viscosity light-curing adhesive resin. Teeth were fixed and evaluated histopathologically. Pulpal responses at 3 days showed only minimal disruption of the odontoblastic zone. At 7 days, the pulps presented reorganizing odontoblastoid cells, and, at 10 days, the pulps showed new odontoblastoid cells with a thin rim of reparative dentin. Pulps of crown preparations that were etched and then sealed with the 4-META system presented healing patterns similar to those of pulps associated with Class V preparations lined with calcium hydroxide, observed in (previous) similar studies. PMID- 7991770 TI - Correction of Class II, division 1, malocclusion with the use of an activator appliance: a case report. AB - This article describes the use of an activator appliance to treat a Class II, division 1, malocclusion in a child in the mixed-dentition phase. The correction of Class II, division 1, malocclusions can be achieved by careful case selection of a motivated patient with a favorable growth pattern. PMID- 7991771 TI - Conservative amalgam restoration of Class II lesions--the "slot" restoration: a case report. AB - The decline in caries prevalence and a greater emphasis on preventive measures and oral hygiene have led to a reconsideration of the classic parameters proposed by Black for cavity preparation. Through a case report, the rationale and the technique for conservative amalgam restoration of interproximal lesions (the slot restoration) are discussed. PMID- 7991772 TI - In vivo evaluation of glass-ionomer cement adhesion to dentin. AB - Class V cavities were prepared in 20 vital teeth and 10 extracted teeth. For all the restorations, glass-ionomer cement was used as a liner at the base of the cavity. The cavity was then restored with a microfilled composite resin. After the extraction of the vital teeth, all specimens were sectioned and tested for marginal microinfiltration of 2% methylene blue dye. The teeth restored in vivo showed no signs of infiltration between the dentin and the glass-ionomer liner. The dye penetrated between the liner and the composite resin in five in vivo restorations. The in vitro restorations dye was present between the dentin and the liner. Examination of replicas under the scanning electron microscope revealed no gaps between the glass-ionomer cement and the dentin in the in vivo specimens, while gaps of various sizes were present in the in vitro replicas. Glass-ionomer cement was able to bond to dentin when used as a liner in vital teeth but not when used in extracted teeth. This can be attributed to the presence of a partially humid environment in vivo that favors the application process. In vitro, specimens are to a large extent dehydrated. PMID- 7991773 TI - The effect of dentinal conditioning on light-activated glass-ionomer cement. AB - This article reports the effect of conditioning of dentinal surfaces on the sealing capability of a light-curing glass-ionomer restorative material, Fuji II LC. The in vitro evaluation measured gap formation at the tooth-restoration interface. The control specimens were restored with Fuji II LC after dentinal surface treatment with a polyacrylic acid solution, while the experimental specimens were restored without pretreatment. The sealing ability of the material to dentin was assessed by measuring the gap between the restorative material and tooth structure. The control group registered a mean marginal gap of 7.75 microns, and the experimental group registered a mean gap of 10.75 microns, but statistical analysis indicated that there was no significant difference between the two groups. Dentinal surface treatment prior to restoration with the light curing glass-ionomer cement used in this study resulted in a smaller gap at the dentin-restoration interface, but this difference was not significant. PMID- 7991774 TI - Logos: the emblem in the marketing wars. AB - The logo is a powerful marketing tool. It is a condensed form of communication for a selected niche in a mass audience. Effective logo design principles include considerations of art design, visual perception, memory retention, and succinct nonverbal communication. Design principles for logos for dental practices are presented. Dental practices may realize significant advantages if logos are properly conceived and executed and are creatively implemented. PMID- 7991775 TI - Prostaglandin F2 alpha stimulates progesterone secretion by porcine luteal cells in vitro throughout the estrous cycle. AB - In this study we examined the stimulatory effects of PGF2 alpha on progesterone secretion by porcine luteal cells on different days of the estrous cycle, and the effects of PGF2 alpha, A23187 and PMA on progesterone secretion by isolated large and small luteal cells, in vitro. Corpora lutea were obtained from cycling pigs (days 6-16), collagenase dispersed and luteal cells incubated in medium 199 in the absence or presence of increasing doses of PGF2 alpha, A23187, and PMA. Progesterone concentrations in spent media were measured by RIA. PGF2 alpha stimulation of progesterone secretion by mixed luteal cells did not vary significantly throughout the estrous cycle. Progesterone secretion by large, but not small, luteal cells was increased (p < 0.05) in a dose-dependent fashion by PGF2 alpha. A23187 also caused a dose-dependent increase in progesterone secretion by large luteal cells but inhibited small luteal cells. Progesterone secretion by both large and small luteal cells was significantly increased by increasing doses of PMA. We conclude that the stimulatory response of luteal cells to PGF2 alpha in vitro did not correlate with PGF2 alpha receptor concentrations (not measured in this study), and we speculate that calcium/protein kinase C may be involved in mediating the stimulatory action of PGF2 alpha on luteal cell progesterone secretion. PMID- 7991776 TI - An endogenous inhibitor of prostaglandin synthesis in human decidua. AB - Human first trimester decidual tissue has been reported to contain an inhibitor of cyclo-oxygenase enzyme, but a careful reading of the literature indicates that the inhibitor may be human albumin. Our own studies also showed that high levels of albumin were present in samples from homogenised decidual tissues. We therefore digested the tissue to obtain isolated cells and washed them extensively to minimise contamination with blood. Homogenates of such cells did not bind arachidonic acid, and inhibited cyclo-oxygenase enzyme-1 (COX-1) activity. The cellular factor inhibited COX-1 at concentrations of 60-100 micrograms protein/ml, and was therefore more potent than human albumin (0.5-2.0 mg/ml). The inhibitory activity was lost after heat treatment (100 degrees C for 10 mins) and after digestion with trypsin or papain, but was resistant to mercaptoethanol and urea. Preliminary data indicated that the protein had a molecular weight > 30 kD. PMID- 7991777 TI - The expression of phospholipase A2 and lipocortins (annexins) I, II and V in human fetal membranes and placenta in association with labour. AB - We have studied the expression of the cellular, type two phospholipase A2 and lipocortins (annexins) I, II and V in human amnion, chorion-decidua and placenta using northern analysis. We found no difference in the expression of phospholipase A2 or lipocortin V in tissues obtained before or after labour. Lipocortin I expression was found to decrease in amnion and placenta but increase in chorion decidua with the onset of labour, while expression of lipocortin II increased only in amnion. These results support the hypothesis that the increased phospholipase A2 activity in the fetal membranes and placenta which is associated with labour is not due to increased phospholipase A2 gene expression, but that post translational control of phospholipase A2 activity may be mediated through changes in lipocortin I expression. PMID- 7991778 TI - Effect of oxytocin and indomethacin on the estrous cycle of goats. AB - The effect of oxytocin and indomethacin on luteal function during the estrous cycle in goats was investigated. Daily subcutaneous administration of oxytocin given on days 12-15 of the estrous cycle had no effect on length of the cycle or concentrations of progesterone and estradiol-17 beta. Oxytocin given on days 3-6 shortened the cycle and decreased concentrations of progesterone, but increased the estradiol-17 beta to levels similar to seen at estrus. These changes caused by oxytocin were prevented by indomethacin, a prostaglandin synthetase inhibitor, although indomethacin given alone did not affect luteal function. These results suggest that luteal function affected by prostaglandin in the early luteal phase of goats may be different from that in cattle. PMID- 7991779 TI - Total content of prostaglandin F2 alpha in the endometrium and myometrium from various sections of the porcine uterine horn during the estrous cycle. AB - The purpose of this study was to determine effects of various stages of the estrous cycle on the content and concentration of PGF2 alpha in endometrium and myometrium in different segment of the uterine horn and whether different methods of expressing PGF2 alpha data would affect interpretation of results. Total content of PGF2 alpha in the endometrium and myometrium of the entire uterine horn, and PGF2 alpha concentrations in five sections of uterine horn each of equal length (1 to 5 beginning from the ovarian end) were measured in gilts during three different phases of the estrous cycle: the early luteal phase (Days 3 to 6 of the estrous cycle), mid-luteal phase (Days 9 to 12), and during luteolysis (Days 15 to 18). The total content of PGF2 alpha in the early and mid luteal phases was similar (P > or = 0.05) in both the endometrium and myometrium. During luteolysis the content of PGF2 alpha in the endometrium and myometrium increased 7-fold and 4-fold, respectively, when compared to the early luteal phase. The distribution of PGF2 alpha was similar throughout the length of the uterine horn and this did not change during the phases of the cycle studied. The PGF2 alpha concentrations during different phases of the estrous cycle differed with methods of expressing the data i.e. ng g-1 tissue, ng mg-1 DNA, ng mg-1 protein, but the relative differences were not appreciably altered. PMID- 7991780 TI - Peripheral and local regulators of folliculogenesis. AB - The role of the gonadotrophins follicle-stimulating hormone (FSH) and luteinizing hormone and the putative local regulators, activin and follistatin, in the control of folliculogenesis is reviewed. An account of early work on the development and application of assays for FSH and inhibin is given, together with a summary of the data on the ovarian responsiveness to gonadotrophin and follicular atresia. Models for studying local regulation of granulosa cells in vitro are described and the data from these experiments reviewed. It is concluded that activin has a role in the development and maintenance of healthy oestrogenic follicles, preventing premature luteinization, whereas follistatin opposes these effects of activin and promotes luteinization or atresia. PMID- 7991781 TI - The role of cortisol in preparing the fetus for birth. AB - The glucocorticoids, cortisol and corticosterone, have a unique function in the fetus in inducing a wide range of enzymes before birth that have little or no function during fetal life but on which survival after birth is dependent. The loss of the placenta at birth deprives the fetus of a source of oxygen, glucose and heat (among many other things) for which alternatives must be available immediately if survival is to be assured. In anticipation of these needs several organs undergo maturational changes in late pregnancy aimed at meeting these requirements. The lungs mature structurally and functionally, becoming distensible and capable of coping with high surface tension when air enters the alveoli with the first breath. In the liver, glycogen accumulates and gluconeogenesis is initiated to meet the demands for glucose until feeding begins. There is an increase in the production of tri-iodothyronine and catecholamines in preparation for the sharp increase in metabolic rate and thermogenesis associated with breathing and the cold environment. All these dramatic maturational events are regulated by cortisol as are numerous others in most organ systems that contribute to neonatal well-being but on which survival is less dependent. Pharmacological manipulation of these systems before birth has made a substantial contribution to improving human health. PMID- 7991782 TI - Hormonal control of testicular descent and the cause of cryptorchidism. AB - This paper briefly reviews the literature on testicular descent and presents new observations from the authors' laboratory which suggest new ways of looking at old problems. There is now good evidence that testicular descent occurs in two morphologically and hormonally distinct phases. Relative 'transabdominal migration' of the testis compared with the ovary occurs at 10-15 weeks of gestation in the human and 'inguinoscrotal' migration occurs at 26-35 weeks of gestation. We have proposed previously that the first phase is controlled by Mullerian inhibiting substance although this remains controversial. The second phase is androgen dependent and is possibly mediated indirectly through the release from the genitofemoral nerve (GFN) of the neuropeptide calcitonin gene related peptide (CGRP). Recently we have used three different rodent models of undescended testis to determine the involvement of the GNF and/or CGRP. The testicular feminization mouse with complete androgen resistance and the rat exposed prenatally to the antiandrogen flutamide have a deficiency of CGRP in the GFN. In contrast, the mutant trans-scrotal rat which has normal androgen levels has an excess of CGRP in the GFN. All cryptorchidism models, despite their different primary cause, have in common an abnormality of the GNF and/or CGRP which is consistent with the hypothesis that normal testicular descent in the rodent may be mediated by the GFN. PMID- 7991783 TI - Structure-function relationships and mechanism of action of pituitary and placental gonadotrophins. AB - Data from the author's laboratory on relationships between structure and function of equine luteinizing hormone, follicle-stimulating hormone and choriogonadotrophin as well as their mechanisms of action are reviewed and compared with their human counterparts. Polymorphism of these hormones and problems associated with their purification are discussed as well as the association and dissociation of their alpha- and beta-subunits. The affinity of receptor binding, the superactivity of membrane transduction and homologous desensitization of target cells by non-stimulatory doses of the gonadotrophins are also reviewed. PMID- 7991784 TI - Low molecular weight components in bovine semen diffusate and their effects on motility of bull sperm. AB - Dialysis of diluted semen before cryopreservation is beneficial to sperm survival. This is due to removal of low molecular weight components from seminal plasma that are damaging to sperm. The apparent molecular weights (M(r)) of these components range between 1000 and 12,000 as estimated by gel permeation chromatography and electrophoresis. The detrimental effect on sperm motility is greatest with the components of M(r) between 5000 and 12,000 and with those of M(r) < 1500. Their effect on sperm motility was dependent on concentration. The small molecular weight components were derived from the high molecular weight components of seminal plasma through disaggregation under prescribed conditions. PMID- 7991785 TI - Survival of ram spermatozoa at high dilution: protective effect of simple constituents of culture media as compared with seminal plasma. AB - During incubation of ram spermatozoa at 1 x 10(7) cells mL-1 or less in a simple HEPES-buffered saline medium, high levels of cell death were detected using propidium iodide as a probe of viability (membrane integrity): some 70% of the cells died during 3 h incubation at 37 degrees C. Because the conditions of incubation were similar to those encountered during manipulations for in vitro fertilization, this phenomenon was investigated further. If ram spermatozoa were diluted in an equivalent sucrose-based medium, or if the saline medium was supplemented with 10% seminal plasma, survival was greatly improved (only 5-15% died during a 3-h incubation at 37 degrees C); the protective effect of seminal plasma resided in a 5-10 kDa fraction. Sperm death in the basal saline medium was strongly dependent on cell concentration below 5 x 10(7) spermatozoa mL-1 whereas little effect of concentration was seen in the sucrose medium or in the presence of seminal plasma. The presence of Ca2+ (2 mM), EGTA (1 mM) or mercaptoethanol (1 mM) enhanced sperm survival in saline medium, but no effect was gained by replacing NaCl with KCl, and neither BSA nor fetal calf serum were beneficial. However, when a combination of pyruvate (1 mM), lactate (21.7 mM), Mg2+ (0.4 mM), phosphate (0.3 mM) and Ca2+ (2 mM) was included in the saline medium (to render it similar to Tyrode's medium), cell survival was greatly improved (12% died during the 3-h incubation).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7991786 TI - Successful embryo transfer following artificial insemination of superovulated fallow deer (Dama dama). AB - Thirty-four European fallow deer (Dama dama dama) were randomly allocated into embryo donor (n = 12) or embryo recipient (n = 22) groups. All does were treated with controlled internal drug release (CIDR) devices for 14 days. Animals in the embryo donor group were further treated with 200 I.U. pregnant mare serum gonadotrophin (PMSG) and 0.5 units ovine follicle-stimulating hormone (FSH). PMSG was administered 72 h before withdrawal of CIDR devices and FSH was given in eight 0.063 unit injections at 12-hourly intervals starting at the time of PMSG administration. All embryo donor animals were inseminated, by laparoscopy in both uterine horns, 36 h after withdrawal of CIDR devices with 25 x 10(6) fresh spermatozoa collected from Mesopotamian fallow deer (Dama dama mesopotamica). Embryos were recovered by laparotomy on Day 3 (n = 6) or Day 6 (n = 6) after withdrawal of CIDR devices and the ovarian response was determined. In total, 22 embryos were transferred into the oviduct (2-4-cell stage, n = 14) or uterine horn (morula stage, n = 8) on Day 3 or Day 6 after withdrawal of CIDR devices respectively. The overall means (+/- s.e.m.) of total follicular response and corpora lutea were 24.2 +/- 3.5 and 14.1 +/- 3.6 respectively. The mean number of large unruptured follicles was higher on Day 6 than on Day 3 (13.5 +/- 2.9 v. 6.7 +/- 1.3, P < 0.05). The overall embryo recovery rate was 45.8%. There was no difference in pregnancy rate following transfer of embryos on either Day 3 or Day 6 (7/14 v. 5/8 respectively).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7991787 TI - Thyroid hormones are required for the expression of seasonal changes in red deer (Cervus elaphus) stags. AB - Experiment 1, from 6 July 1990 (winter) to 8 November 1990 (spring), examined the effect of an early elevation of plasma thyroid hormone concentrations on the expression of seasonal changes in 20-month-old stags. Four stags were injected subcutaneously with 1 mg thyroxine (T4) daily, and four with vehicle only. Plasma T4 concentration was elevated by injection of T4; the mean concentration 24 h after injection was 192 +/- 31 nmol L-1 compared with 58 +/- 5 nmol L-1 in controls on 21 September. However, live weight, testicular diameter, plasma testosterone concentration and moulting underwent similar changes in both groups of animals. Experiment 2 tested the hypothesis that thyroid hormones are required for the expression of changes that occur during spring and early summer in red deer stags. Thyroidectomized (THX) stags (n = 4) of mixed age (> 22 months old) were given a replacement dosage of T4 or vehicle only (controls) during spring (from 7 September). T4-treated THX stags underwent testicular regression, antler regeneration and spring moult during spring and early summer (October-December), whereas control THX stags did not display these changes. During spring and summer, T4-treated stags gained more live weight (P < 0.05) than control stags. These results show that, in stags, thyroid hormones are required for the expression of seasonal changes and that these changes are not caused by the seasonal elevation of plasma concentrations of thyroid hormones. PMID- 7991788 TI - Natural and recombinant bovine interferon tau regulate basal and oxytocin-induced secretion of prostaglandins F2 alpha and E2 by epithelial cells and stromal cells in the endometrium. AB - The effects of bovine interferon tau (IFN tau) and oxytocin on secretion of the prostaglandins PGF2 alpha and PGE2 by epithelial and stromal cells in the endometrium were assessed in two experiments. Endometrial tissues were collected from cyclic cows at Day 15 after oestrus for subsequent isolation of epithelial cells (4 cows) and stromal cells (4 cows). In both experiments, confluent cells were treated with 0, 2, 10 or 50 ng mL-1 natural bovine IFN tau (nbIFN tau) or 0, 0.4, 2, 10, 50 and 250 ng mL-1 recombinant bIFN tau (rbIFN tau). Culture medium was sampled at 24 h. Oxytocin (2.0 x 10(-7) M) or placebo was then added to wells and the medium was sampled 30 and 90 min later. Epithelial cells secreted more PGF2 alpha than stromal cells whereas stromal cells predominantly secreted PGE2. Oxytocin stimulated secretion of PGF2 alpha and PGE2 (P < 0.01) from epithelial cells, but both basal secretion and oxytocin-induced secretion of PGF2 alpha and PGE2 decreased with increasing dose of either nbIFN tau or rbIFN tau (P < 0.01). At comparable doses, rbIFN tau inhibited PGF2 alpha and PGE2 secretion more strongly than did nbIFN tau (either in the absence or the presence of oxytocin). The minimal effective dose of rbIFN tau was 0.4 ng mL-1 and 50% inhibition was obtained with 1 ng mL-1 (0.043 nM). Neither nbIFN tau nor rbIFN tau nor oxytocin altered PGF2 alpha or PGE2 secretion by stromal cells. The results indicate differential prostaglandin responses by the two major endometrial cell types (epithelium and stroma) to regulatory agents such as bIFN tau and oxytocin in cattle. Suppression of prostaglandin secretion by bIFN tau in epithelial cells of endometrial tissue is supportive of an antiluteolytic effect of bIFN tau. PMID- 7991789 TI - Actions of oxytocin and vasopressin on oestrogen-induced electromyographic activity recorded from the uterus and oviduct of anoestrous ewes. AB - Oxytocin and the related peptide [Arg8]vasopressin (AVP) have previously been shown to bind with equally high affinity to oxytocin binding-sites (presumed oxytocin receptors) present within the uterus and oviduct of oestrous ewes. There is a possibility, therefore, that AVP mediates oxytocic actions through these binding sites. For the present study, ewes in seasonal anoestrus were treated with oestradiol-17 beta (50 micrograms subcutaneously, daily for 2-4 days). It was shown initially that this treatment stimulated the development of high affinity oxytocin binding-sites (Kd 4.4 +/- 0.8 nmol L-1) which had similar affinity for AVP (Kd 4.2 +/- 0.9 nmol L-1) in the myometrium. The efficacy of oxytocin and AVP in vivo were compared by recording electromyographic (EMG) activity from the ampullary-isthmic junction of the left oviduct and the left uterine horn of four conscious ewes. Before oestradiol treatment there was no EMG response to oxytocin even at supraphysiological (1000 mU) doses. During oestradiol treatment, EMG activity was consistently increased in response to injections of 25 mU and 100 mU oxytocin via the jugular vein, but not to saline or 100 mU AVP. Higher doses of AVP were not investigated because of the possibility of cardiovascular side effects. A subsequent blood sampling experiment showed that maximal concentrations of oxytocin and AVP (achieved in peripheral plasma during the first 2 min following injection into the jugular vein) were of a similar order of magnitude after injection of equivalent doses of the two peptides. It is concluded that AVP probably does not mediate biological activity through the oxytocin receptor in non-pregnant ewes.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7991790 TI - Porcine conceptus and endometrial retinoid-binding proteins. AB - Porcine conceptus secretory proteins were obtained from medium in which pig conceptuses, collected on Day 15 of pregnancy, were cultured for 30 h. Culture medium was pooled, dialysed and concentrated by Amicon ultrafiltration for retinol and retinoic acid (RA) binding studies. Proteins in the 20-kDa range, conceptus-secreted retinol-binding protein (RBP), bound both [3H]retinol and [3H]RA specifically. Cross-competition experiments indicate that [3H]RA was completely displaced with excess cold retinol; however, excess cold RA did not completely displace [3H]retinol, suggesting that conceptus RBP has greater affinity for retinol than RA. Cellular RBP and retinoic acid receptor (RAR)-alpha and RAR-gamma mRNA transcripts (0.7 kb; 3.8 and 2.8 kb; 3.4 kb respectively) were detected in poly (A)+ RNA isolated from Day-15 conceptus, Day-15 pregnant endometrium, late pregnant myometrium and late pregnant fetal tissues of pigs by Northern blot analysis. RAR-alpha and RAR-gamma immunoreactive proteins were detected in extracts of Day-15 conceptus, Day-15 pregnant endometrium and late pregnant fetal tissues by Western blot analysis. Collectively, results indicate that biochemical molecules required for retinoid transport, metabolism and regulatory effects are present in porcine conceptus and endometrial tissues during early pregnancy in swine. PMID- 7991791 TI - Importance of bicarbonate/CO2 for fertilization of pig oocytes in vitro, and synergism with caffeine. AB - Fertilization of pig oocytes was performed in vitro in modified Tyrode's media in which either HEPES or bicarbonate/CO2, or both, were included as buffer systems; caffeine (2 mM) was also included in some of the media because it is a reported stimulant of fertilization. The composition of the bicarbonate-containing media was designed so as to maintain the same pH and osmolality as bicarbonate-free media. The inclusion of bicarbonate during gamete co-incubation in caffeine containing medium led to high levels of fertilization (66% of 238 mature oocytes were fertilized). However, essentially no fertilization occurred if bicarbonate was replaced with HEPES (0.7% of 146 oocytes were fertilized; significantly different, P < 0.001). Inclusion of HEPES in bicarbonate-containing medium during gamete co-incubation did not affect fertilization, showing that HEPES did not exert an inhibitory effect. Omission of bicarbonate during sperm preincubation also did not affect fertilization. If caffeine was included in bicarbonate containing medium, 73% of 311 oocytes were fertilized whereas if caffeine was omitted only 14% of 326 oocytes were fertilized (significantly different, P < 0.001). In the absence of bicarbonate, when fertilization was very low, caffeine had no stimulatory effect. The results indicate that bicarbonate is essential for pig fertilization in vitro, but that caffeine exerts a synergistic stimulatory effect. PMID- 7991792 TI - Effect of culture in vitro and organ culture on the dry mass of preimplantation mouse embryos. AB - The dry mass of mouse embryos cultured in vitro in medium alone or in an organ culture system were measured by means of the Vickers M86 scanning microinterferometer. The data were compared with previous data on the dry mass of preimplantation embryos in vivo. The metabolism of embryos cultured in vitro differs from that of fresh embryos. In cultured embryos, dry mass decreases throughout the 2-cell stage whereas the dry mass is increasing at this stage in vivo. Embryos in an organ culture system regain a dry mass profile, similar to that observed in vivo at the late cleavage stage. These results support the view that conditions for embryo metabolism are suboptimal in vitro and that, although the oviduct may confer some advantage on developing embryos in vitro, it is unable fully to support the pattern of metabolism, as assessed by dry mass, observed in vivo. PMID- 7991793 TI - Silastic implants for delivering physiological concentrations of progesterone to mice. AB - Silastic implants filled with progesterone in arachis oil were designed to provide a convenient and reliable method for the delivery of physiological concentrations of progesterone to mice. Placement of the implants in ovariectomized mice resulted in a rapid increase in circulating progesterone within 6 h; stable levels could be maintained for many days. Removal of the implants resulted in a very rapid fall in progesterone concentrations. The delivery of progesterone from the implants could be controlled by varying both the length of the implants and the concentration of progesterone internally. This allowed plasma progesterone concentrations to be maintained and controlled over the entire physiological range. PMID- 7991794 TI - Effect of a new anti-oestrogen and anti-implantation agent, CDRI-85/287, on tubal transport, development and viability of rat embryos. AB - The effect of CDRI-85/287, a pure nonsteroidal anti-oestrogen, on the rate of tubal transport and development and viability of embryos in rats was investigated. Single postcoital oral administration of an anti-implantation dose (2.5 mg kg-1) resulted in a mild acceleration in the passage of embryos through the oviduct; however, their rates of recovery, cleavage, blastocyst formation and zona shedding remained unaffected. Morphologically normal embryos were recovered from the genital tract up to Day 12 post coitum. Embryos recovered from CDRI 85/287-treated rats on Days 4 and 8 post coitum developed to normal term fetuses when transferred to uteri of untreated females. The compound therefore did not seem to have any deleterious direct effect on development or viability of rat embryos. PMID- 7991795 TI - Superovulation and embryo recovery in ewes treated with gonadotrophin-releasing hormone agonist and purified follicle-stimulating hormone. AB - Chronic treatment with gonadotrophin-releasing hormone (GnRH) agonist eliminates luteinizing hormone (LH) pulses and inhibits maturation of Graafian follicles in sheep. Since the presence of 'dominant' follicles may inhibit superovulatory responses, an experiment was conducted to determine whether a GnRH agonist could be used in conjunction with follicle-stimulating hormone (FSH) to induce a superovulatory response with production of normal embryos. Twenty-four Welsh Mountain ewes were chronically treated with GnRH agonist by means of a subcutaneous minipump. Twelve of the ewes were given 12 mg progesterone intramuscularly (i.m.) twice daily for four days; all ewes were then given 672 micrograms (total) of highly purified FSH continually infused intravenously for either 72 h (Group A) or 96 h (Group B) in a 2 x 2 experimental design (n = 6). Ovulation was then induced with 750 I.U. human chorionic gonadotrophin injected i.m. (Day 0) and all ewes were inseminated into the uterus with > 100 x 10(6) fresh sperm on Day 0. Embryos were flushed from the uterus, and ovaries were inspected at laparotomy on Day 5. Pretreatment with progesterone did not affect any of the parameters measured and data were pooled accordingly. There were no differences between Groups A and B in the number of ovulations or the number of embryos recovered, although there were more large unruptured follicles in Group A animals (8.8 +/- 0.8 v. 3.1 +/- 0.7, P < 0.001). The embryo recovery rate was higher in Group A ewes (52.5 v. 26.4, P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7991796 TI - Effect of post-ovulation nutritional status in ewes on early conceptus survival and growth in vivo and luteotrophic protein secretion in vitro. AB - Overfeeding during early pregnancy in ewes compromises pregnancy establishment and/or embryo survival. To determine whether high feed intakes after ovulation alter the secretory dialogue between the conceptus and the endometrium, 24 embryos (8-16-cell) from ewes fed maintenance rations were synchronously transferred in singleton on Day 3 of the cycle (oestrus, Day 0) into the uterus of ewes receiving a high or low plane of nutrition from Day 0 (n = 12 ewes per group). Embryo survival and conceptus growth were assessed on Day 16. At this time, pregnancy was maintained in 11 of 12 recipient ewes per group and conceptus mass was not influenced by nutritional plane (637 +/- 48 v. 583 +/- 72 mg for high and low groups respectively). Conceptus and endometrial tissues were cultured separately for a further 24 h in vitro in the presence of [3H]leucine. There was no quantitative difference between nutritional treatments in the incorporation of radiolabel into proteins synthesized and secreted by the conceptus or endometrium. Secretion of ovine trophoblast protein-1 was also similar in both groups. Peripheral progesterone concentrations were significantly (P < 0.05) lower throughout the luteal phase in recipient ewes on high v. low intakes after ovulation. This effect was independent of ovulation rate which was 3.1 +/- 0.40 and 2.6 +/- 0.25 corpora lutea for high and low groups respectively. A high plane of nutrition after ovulation did not influence embryo survival and development in vivo or luteotrophic protein secretion in vitro despite a reduction in peripheral progesterone concentrations.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7991797 TI - Influence of day-0 and day-7 superovulated cow serum during development of bovine oocytes in vitro. AB - Oocytes were matured in medium supplemented with 5% serum collected from superovulated cows at oestrus (Day-0 SCS) or at the time of embryo collection (Day-7 SCS), or in medium supplemented with fetal calf serum (FCS). After insemination using frozen-thawed sperm, oocytes were cultured in vitro with medium supplemented with 5% Day-0 SCS or 5% Day-7 SCS or 5% FCS. The proportions of embryos that cleaved were not significantly different among treatments, whereas development of the embryo to a blastocyst was significantly higher in the presence of SCS than FCS. When the four possible combinations of Day-0 SCS and Day-7 SCS were used in the maturation and culture media, there were no differences among treatments, except that the cleavage rate was significantly higher (P < 0.05) with Day-0 SCS in the maturation medium and Day-7 SCS in the culture medium than with Day-7 SCS in the maturation medium and Day-0 SCS in the culture medium. The proportions of embryos that cleaved and developed to blastocysts were not related with the level of progesterone and luteinizing hormone in the serum added to the maturation and culture media. However, the use of serum with low concentrations of glucose, fatty acids and cholesterol in the maturation medium and the culture medium tended to be associated with a higher rate of cleavage and blastocyst development. PMID- 7991798 TI - Effect of active immunization against the amino-terminal peptide (alpha N) of the alpha 43 kDa subunit of inhibin (alpha 43) on fertility of ewes. AB - Immunization against the amino-terminal peptide (alpha N) of the alpha 43 subunit of inhibin was shown previously to reduce fertility in ewes. The aim of this study was to examine the effects of active immunization of ewes against alpha N on egg recovery and fertilization rates. Ewes were immunized against alpha N immunogen, and were given 800 I.U. of pregnant mare's serum gonadotrophin at the end of treatment with intravaginal progesterone to synchronize the oestrous cycles. Control ewes received adjuvant only. The ewes were run with fertile rams, and 4 days after withdrawal of the progesterone device the oviducts were flushed to recover eggs and luteal structures on the ovaries were recorded. Eggs were recovered from 17/19 (90%) control ewes compared with 4/16 treated ewes (25%) (P < 0.01), and the egg recovery rates were 76% (45/59) and 17% (7/42) respectively (P < 0.001). The mean number of corpora lutea (CL) per ewe were similar (3.1 +/- 1.4 v. 2.6 +/- 1.0) but several CL in the treated ewes did not appear to have ruptured, and 2 treated ewes had cystic follicles and no CL. There were no apparent differences in either the fertilization rates or the stages of development of fertilized eggs between treated and control ewes. Antibody binding levels in follicular fluid were approximately half those found in peripheral plasma. It is concluded that immunization of ewes against alpha N leads to lowered fertility by suppressing ovulation, implicating alpha N in the normal ovulatory process. PMID- 7991799 TI - Oxytocin stimulates uterine prostaglandin F2 alpha secretion in red deer Cervus elaphus. AB - The prostaglandin F2 alpha analogue cloprostenol stimulates ovarian secretion of oxytocin in red deer hinds and Pere David's deer hinds, as in cattle and sheep, but the response of the uterus to administered oxytocin has not been studied in deer. In the present experiment, oxytocin administered intravenously caused an increase in circulating concentrations of 13,14-dihydro-15-keto prostaglandin F2 alpha from 186 +/- 35 to 404 +/- 34 pmol L-1 within 5 min; concentrations in saline-treated hinds were unchanged (150 +/- 12 and 164 +/- 12 pmol L-1 before and after treatment respectively). This suggest that in red deer as in other ruminants, a positive feedback relationship between the corpus luteum and the uterus may operate to stimulate luteolytic episodes of prostaglandin F2 alpha. PMID- 7991800 TI - [The Prader-Willi syndrome. A diagnostic update]. AB - The authors analyze the clinical history of a 13-year-old boy with the diagnosis of Prader-Willi syndrome (PWS), who was studied in the Perinatal Pediatric Neurology and Clinical Genetics outpatient clinics, in the Social Security Arnulfo Arias Madrid Hospital Complex. The authors review the clinical characteristics that help in the diagnosis of PWS, in the neonatal period and therefore increase the rate of early diagnosis. PMID- 7991801 TI - [The neurobiological bases of aggression: the pharmacotherapeutic implications]. AB - The aim of this paper is to attempt a classification of aggressive behavior based on neurobiological mechanisms and to shed some light on the pharmacological treatment of this condition. Drugs that enhance serotonin transmission are indicated in conditions related to decreased serotonergic transmission. Dopamine blockers are useful in the acute control of aggression and the violence displayed by schizophrenic patients. Clozapine probably has an anti-aggressive effect independent of its antipsychotic action. Noradrenergic agents have been shown effective in chronic aggression of organic brain syndromes. Gabaergic drugs are effective in acute aggression and in organic brain syndromes. PMID- 7991802 TI - [The isolation of Schizophyllum commune in Panama]. AB - The authors report the isolation of the basidiomycete Schizophyllum commune in two enclosed areas of healthy facilities in the city of Panama. The growth occurred in Sabouraud's agar as a white mycelium which gradually rose above the surface of the culture medium until it became a fan-shaped basidiocarp. This basidiomycete is found in environmental samples, but since there have been reports of its role in pathologic processes it should be included in the etiologic differential diagnosis in some patients and clinical laboratory must identify it and not discard it as a "contaminant". PMID- 7991803 TI - [Epithelioid sarcoma. A clinical, pathological and immunohistochemical analysis]. AB - The author study the clinical history of a patient who initially had a nodule in the left arm and the lesion was excised, had 7 recurrences in the left arm in the following twelve years. The histological examination of one of the nodules showed that it was composed mainly of large ovoid and polygonal cells with abundant eosinophilic cytoplasm, vesicular nuclei and prominent nucleoli. There was an average of 4 mitoses in every 10 high power fields and rare atypical mitoses. The tumor cells showed intense activity with keratin, epithelial membrane antigen and vimentin, and were negative for the CD 31 endothelial marker. PMID- 7991804 TI - [The psychological factors that affect the making of a decision for surgical sterilization and the likely later changes]. AB - The practice of female surgical sterilization in Panama during the past decades, motivated the realization of this study, to determine the factors which caused women to use this permanent contraceptive method, and to see if regrets later occurred after that decision, in the sterilized women. A sample of 151 women were selected, between the ages of 28 and 45 years, concurrently pregnant and with 2 or more living children at the moment of the study. Psychological tests were applied during three different phases (pre-operatively and subsequently 12 and 24 months, post operatively). Results showed that female sterilization did not cause long term complications, and amongst the majority of women conforming the sample, a stable psychological profile was found up to 24 months after the interventions, with a significant improvement in the last evaluation of the social adaptation variable, in comparison to the pre-operative assessment. PMID- 7991805 TI - [Abdominal tuberculosis]. AB - The authors studied the symptoms, signs and diagnostic procedures in 9 cases of abdominal tuberculosis, six in women, three in men, 17 to 84 and average of 43 years old, who were treated in the Social Security Arnulfo Arias Madrid Hospital Complex in Panama City. In 8 cases the diagnosis was confirmed by biopsy with laparotomy, in 5 with laparoscopy in 1 case because by concomitant lung tuberculosis and improvement with antituberculosis drugs. They present the clinical histories of 2 patients in order to discuss the presenting complaints in abdominal tuberculosis, review the pathology and arouse interest in the study of this entity precisely now that since the initiation of the AIDS epidemic in Panama in 1984 until July 1992 there have been a total of 369 confirmed cases of which 18% had tuberculosis as the first or second opportunistic infection. PMID- 7991806 TI - [Anorectal malformations: their diagnosis and the initial decisions]. AB - The author presents the salient aspects of anorectal malformation which allow us to simplify their anatomical diagnosis. In many cases only clinical means are used while in others adequate use of technical studies are necessary. This enables us to reach therapeutic decisions in the simplest and most orderly fashion so that patients with these anomalies may be given the opportunity of attaining normal or near normal function. PMID- 7991807 TI - [The history of family planning among women who opt for surgical sterilization in the Social Security Fund of Panama]. AB - In this study, the previous history of family planning and prior usage of contraceptive methods are analyzed, in a sample of 175 women who voluntarily opted for surgical sterilization as a permanent method of fertility regulation, in the Panamanian Social Security System. A questionnaire was applied during the second trimester of pregnancy, by which information would be gathered in regard to knowledge, usage and adverse effects of the contraceptive methods used prior to the intervention. Results showed that 99% of the sample had heard, on some occasion about oral contraceptives (OC) and, in lesser proportion to intrauterine devices (IUD), barrier methods and hormonal inyectables. The first contraceptive method used, and the one of longest usage, was the combined OC, of which 43% begun between 17 and 25 years of age. In contrast, 7.4% initiated contraception with IUD, from the age of 26 years. The health personnel constituted the major source of recommendation for contraceptive usage and, despite the fact that 37% of the sample did not use contraception prior to the last pregnancy, over half of the subjects responded that combined OC were considered as the most secure method. PMID- 7991809 TI - High tech equals high cost in medicine: does it really? PMID- 7991808 TI - [The syndrome of renal and pulmonary vasculitis with positive neutrophil anticytoplasmic antibodies and antibasement membrane antibodies. A case report]. AB - The authors present a case of Goodpasture's syndrome with necrotizing vasculitis of spleen and appendix. Serological examination shows antiglomerular basement membrane antibodies and antineutrophil cytoplasmic antibodies. The authors review the literature to establish if this or other similar cases can be considered a distinct disease entity. The authors also mention the laboratory methods that are currently being used to classify more precisely the vasculitides associated with glomerulonephritis. PMID- 7991810 TI - Cholangiographic segmental anatomy of the liver. AB - The importance of understanding the Couinaud nomenclature describing hepatic segmental anatomy has been increasingly recognized by practicing radiologists. The normal cholangiographic appearances of the biliary ductal branches, as well as those of their common anatomic variants, are less well known. As percutaneous biliary procedures increase in frequency and complexity, a thorough understanding of this anatomy is of utmost importance. In this article, we present cholangiograms, computed tomographic (CT) scans, and anatomic drawings to illustrate cholangiographic segmental anatomy and its correlation with segmental anatomy as depicted by CT. The significance of the anatomy to percutaneous interventional procedures is discussed. PMID- 7991812 TI - MR imaging of hemorrhage and iron deposition in the kidney. AB - Hemoglobin and its degradation products result in signal intensity changes at T1- and T2-weighted magnetic resonance imaging that can either facilitate or obstruct diagnosis of renal lesions. These substances are deposited in the kidney by means of hemorrhage or systemic intravascular hemolysis. Hemorrhage commonly occurs into a renal cyst, resulting in an appearance that cannot be reliably distinguished from that of renal cell carcinoma without use of contrast material. Hemorrhage may also occur diffusely in the renal medulla, and the resulting low signal intensity on T1- and T2-weighted images is characteristic of the rare disease hemorrhagic fever with renal syndrome. Systemic intravascular hemolysis results in low signal intensity in the renal cortex on T2-weighted images, owing to hemosiderin deposition; this occurs in severe hemolytic anemias. Familiarity with the spectrum of findings in the kidney resulting from hemorrhage or iron deposition is necessary for accurate diagnosis of renal disease. PMID- 7991811 TI - State-of-the-art MR imaging of the adrenal gland. AB - The authors discuss the appearances of adrenal diseases characterizable with magnetic resonance (MR) imaging (pheochromocytomas, hemorrhage, cysts, adenomas, myelolipomas, and metastases), new imaging techniques, and differentiation of benign from malignant lesions. Most pheochromocytomas appear markedly hyperintense relative to the liver on T2-weighted images. However, this appearance is not specific, since adrenal metastases and adenomas may have similar features. Occasionally, pheochromocytomas may be iso- or hypointense to the liver on T2-weighted images. One of the new techniques for MR imaging of the adrenal gland, fat suppression, reduces cardiac and respiratory motion-induced artifacts, accentuates small differences in tissue contrast, and eliminates chemical shift artifacts. These advantages far outweigh the disadvantages of inhomogeneity of fat suppression and the fewer sections obtained per acquisition. Differentiation of adrenal metastases from adrenal adenomas with MR imaging is problematic with the use of signal intensity ratios (33% overlap) or T2 calculations. The future of discriminating between adrenal metastases and adenomas may rest with chemical shift MR imaging, which uses in-phase and out-of phase gradient-echo pulse sequences. This approach relies on the fact that adrenal adenomas contain fat whereas metastases do not. The reported accuracy of chemical shift imaging in differentiating adrenal adenomas from metastases is 96% 100%. PMID- 7991813 TI - Echo-planar imaging. AB - Echo-planar imaging is a fast magnetic resonance (MR) imaging technique that allows acquisition of single images in as little as 20 msec and performance of multiple-image studies in as little as 20 seconds. Echo-planar imaging achieves its speed by obtaining all spatial-encoding information after a single radio frequency (RF) excitation. Conventional imaging requires multiple-RF excitations, separated by the repetition time (TR), to acquire this information. An "infinite" TR, routine lipid suppression, and sensitivity to magnetic susceptibility are other features of echo-planar imaging. Standard pulse sequences are used to obtain echo-planar images, which have diagnostic utility similar to that of conventional MR images. Echo-planar imaging is less sensitive to motion than is conventional MR imaging and allows imaging of rapidly changing physiologic processes such as blood flow and kinetic activity. Echo-planar imaging is opening new areas of MR imaging research and clinical applications. PMID- 7991814 TI - Differential diagnosis of leukokoria: radiologic-pathologic correlation. AB - Leukokoria is an abnormal pupillary light reflection that usually results from an intraocular abnormality and is seen most often in children. One-half of the cases of childhood leukokoria are caused by retinoblastoma, a malignant tumor of immature retinoblasts that manifests in a normal-sized eye as a calcified mass, is often partially necrotic, and grows into the vitreous and through the choroid. Retinoblastoma enhances with contrast material and, unlike most tumors, may be darker than vitreous on T2-weighted images. When leukokoria is associated with microphthalmia, persistent hyperplastic primary vitreous (PHPV) (28% of cases) or retinopathy of prematurity (ROP) (5% of cases) should be considered. PHPV is a congenital, usually unilateral lesion that appears as a dense tubular mass extending from the lens to the retina along the course of the hyaloid canal. Hemorrhage from PHPV produces a subhyaloid (or subretinal) fluid collection, often with characteristic blood-fluid levels. ROP is bilateral and usually manifests in premature infants who received supplemental oxygen therapy. Coats disease (16% of leukokoria) is a sporadic unilateral idiopathic retinal telangiectasia that produces a lipoproteinaceous subretinal exudate leading to complete retinal detachment. The globe has normal size but increased attenuation and signal intensity from hemorrhage without calcification or enhancement. Toxocaral endophthalmitis (16% of leukokoria) is a granulomatous reaction to the parasite in the vitreous and uveoretinal coat. Retinal astrocytoma (3% of leukokoria), which manifests in a normal-sized globe, is an indolent benign neoplasm commonly associated with phakomatoses (usually tuberous sclerosis). PMID- 7991815 TI - MR imaging instrumentation and image artifacts. AB - Current magnetic resonance (MR) imaging systems use four basic types of magnets: permanent, resistive (electromagnets), hybrid (combines principles of permanent and resistive magnets), and superconducting (resistive-like magnets cooled to near absolute zero to achieve superconductivity). The first three have relatively low field strength (0.2-0.6 T) compared with superconducting magnets (2.0 T), but they cost less, have limited fringe fields, and have minimal sitting restrictions. Although current low-field-strength units have signal-to-noise ratios competitive with those of high-field-strength superconducting units, the latter still allow faster data acquisition. Use of shim coils improves the uniformity of the primary magnetic field and thus image quality. However, distortions may be incurred depending on the magnetic susceptibility of materials being imaged or chemical shift effect. Image nonuniformities can result from the interactions between the shim coils and gradient coils, which are used to create the high-performance linear gradients needed in many MR techniques (eg, gradient echo and echo-planar imaging). The gradient coils must be shielded to prevent these eddy current effects. The imager must also be shielded from external radio frequency signals, which can cause interference. Image degradation caused by respiratory motion, cardiac motion, and blood flow can be reduced by use of gating and special imaging techniques. PMID- 7991816 TI - Understanding the process of quantitative ultrasonic tissue characterization. AB - Because the human vision system cannot distinguish the broad range of gray values that a computer visual system can, computerized image analysis may be used to obtain quantitative information from ultrasonographic (US) real-time B-mode scans. Most quantitative US involves programming an off-line computer to accept, analyze, and display US image data in a way that enhances the detection of changes in small-scale structures and blood flow that occur with disease. Common image textural features used in quantitative US tissue characterization consist of first-order gray-level statistics (eg, occurrence frequency of gray levels independent of location or spatial relationship) and second-order gray-level statistics dependent on location and spatial relationship, including statistical analysis of gradient distribution, co-occurrence matrix, covariance matrix, run length histogram, and fractal features. A customized tissue signature software has been developed to analyze image data obtained from clinical US scanners. Means comparison testing and multivariate analysis techniques are used to compare the numbers generated for a particular region of interest. By integrating these techniques into the radiologist's interpretation of the sonogram, the quantitative information gained may lead to earlier detection of lesions difficult to see with the human eye. PMID- 7991817 TI - Diagnostic imaging management in Manitoba: 1995-2000. AB - As part of a 5-year imaging management plan being developed for the single insurance carrier in Manitoba, the radiologic utilization for the province was reviewed. For the fiscal year 1993 (April 1, 1992, through March 31, 1993), 1,056,694 imaging studies were performed in a total patient population of 1,133,117 in 81 hospitals and 39 offices in which 648 units of equipment were operated by 773.4 full-time personnel at a cost of $100,302,812 ($75,227,109 in U.S. dollars). The skin dose for the total population for the year was 40,112 Gy, compared with 35,513 Gy in 1979. Since 1979, there has been a 9% increase in the number of radiologic examinations (from 972,426 examinations), a greater need for more personnel to conduct ultrasound, mammography, computed tomography, and magnetic resonance imaging examinations, and striking costs escalation (from $25,082,500 to $100,302,812). Reduction of total funding for imaging services will be possible only if the medical service infrastructure and physician behavior are altered, since imaging is a support service. Hospital services must be integrated and the infrastructure reduced, and physicians must adhere to guidelines and practice protocols for requesting consultations. PMID- 7991818 TI - Digital archive system for radiologic images. AB - Use of a picture archiving and communication system (PACS) for clinical review requires rapid access to patient images. The authors have developed a second generation archive system for a departmental PACS that optimizes access time for both current and historical images. The system is based on a composite staging mechanism that uses multiple storage media: magnetic disks, erasable magneto optical disks, and write-once-read-many (WORM) disks. A two-tiered communication network composed of a standard Ethernet network and a gigabit bandwidth fiberoptic UltraNet network is used for distributing images to remote display stations. The system currently archives 1.5 Gbytes of radiologic images daily from three magnetic resonance imagers, two computed tomographic scanners, one computed radiographic system, and one laser film digitizer. The system features (a) multiple optical drives and robotic arms, which support concurrent archival and retrieval operations; (b) a stacking mechanism, which provides fast retrieval of current images; (c) a pre-fetch mechanism, which minimizes on-line image retrieval, hence relieving peak-hour workload of the optical disk library and the networks; (d) studies grouping and platter management, which optimize retrieval of a patient's images from multiple examinations; and (e) a job-prioritizing control, which minimizes waiting time for radiologists and referring physicians to review images at the display stations. This system is suitable for a large scale PACS to serve the clinical and research staff. PMID- 7991819 TI - Computerized scientific exhibit in radiology: a valuable format for delivering scientific information. AB - The computerized scientific exhibit (CSE) is gaining acceptance as a tool for delivering scientific information at meetings of radiologic societies. CSEs allow presentation of more material in a more space-efficient manner than do conventional exhibits, and the viewer can control the order and detail in which material is reviewed. As a disadvantage, currently, the radiologist must use a support team and learn new tools to create a CSE. The preparation and cost may also be greater. Meeting attendees must overcome a reluctance to use computers to benefit from a CSE. Creation of a CSE has design, production, and presentation phases. A team of content authors, software author, graphics acquisition person, and project manager works together through brainstorming, conceptual ordering, storyboarding, prototyping, and selection of authoring tools to design the exhibit. Production must include use of common word processing and image file formats, as well as standardization of image resolution. Accurate equipment specification is needed to ensure that the exhibit can be run on the equipment provided by the meeting organizers. In addition, some security steps are needed to prevent misuse of the exhibit. In addition to display at assemblies, the CSE can be made available to a larger audience by delivery on media such as compact disks and the Internet and can be continually modified as new material becomes available. PMID- 7991820 TI - Pediatric case of the day. Neurocristopathy (Ondine-Hirschsprung syndrome). PMID- 7991821 TI - General case of the day. Chronic traumatic pseudoaneurysm of the thoracic aorta. PMID- 7991823 TI - Chest screening and tuberculosis in the United States. PMID- 7991822 TI - Ultrasound case of the day. Hepatosplenic candidiasis. PMID- 7991824 TI - Future of diagnostic radiology. PMID- 7991825 TI - Hypoglossal nerve palsy: a segmental approach. AB - Hypoglossal nerve (cranial nerve XII) palsy is uncommon. Damage to this nerve produces characteristic clinical manifestations, of which unilateral atrophy of the tongue musculature is the most important. When these features are recognized, the radiologist, armed with knowledge of the normal anatomy of the area, can focus on each segment of the nerve in search of a cause. The hypoglossal nerve is divided into five segments: the medullary, cisternal, skull base, nasopharyngeal/oropharyngeal carotid space, and sublingual segments. Because each segment is usually affected by different disorders, localizing a lesion to a particular segment allows the radiologist to narrow the differential diagnosis. In this way, the most efficient imaging strategy for evaluation of the symptoms can be developed. Both computed tomography and magnetic resonance imaging are useful in assessing dysfunction of the hypoglossal nerve; the choice depends on the status of the patient and the preference of the radiologist. PMID- 7991826 TI - Percutaneous vascular and nonvascular puncture under US guidance: role of color Doppler imaging. AB - Although ultrasound guidance is extensively used in percutaneous interventional procedures, the limitations of B-mode, gray-scale sonographic guidance can restrict clinical use. Little attention has been paid to the use of color Doppler sonography during such procedures. There are several ways in which color Doppler sonography can facilitate percutaneous procedures that involve insertion of a needle or catheter. The advantages of color Doppler sonography include the following: (a) better visualization of the shaft and tip of the needle, especially in solid, echogenic lesions, when the needle is moving, or when the beam-needle angle is narrow; (b) improved targeting of either vessels or non vascular structures (ie, biliary ducts) to be punctured; (c) avoidance of interposed vascular structures and highly vascular areas during puncture of lesions; (d) improved visualization of poorly echogenic catheters, allowing proper placement; and (e) prompt detection of complications, including active bleeding, after withdrawal of the needle. PMID- 7991827 TI - CT evaluation of the anterior mediastinum: spectrum of disease. AB - Computed tomography (CT) is the study of choice for evaluating disease in the anterior mediastinum. Mediastinal CT is usually performed with intravenously administered contrast material, and spiral CT is the preferred technique for evaluating a mediastinal mass. CT demonstrates thymic hyperplasia and thymic cysts and can help differentiate thymoma and thymic Hodgkin lymphoma. It is also useful in staging Hodgkin lymphoma and non-Hodgkin lymphoma. In thyroid malignancy, CT can depict mediastinal extension and lymphadenopathy; it also allows detection of goiter and ectopic parathyroid glands. Germ cell tumors such as teratoma and seminoma have characteristic appearances at CT. CT can also demonstrate miscellaneous mediastinal masses, such as lymphangioma, hematoma, those due to fibrosing mediastinitis, and pericardial cysts. Adenopathy due to tuberculosis or sarcoidosis is evident at CT, as is osteomyelitis due to a postsurgical abscess. Finally, CT features can suggest the pathologic origin of metastasis in the anterior mediastinum. PMID- 7991828 TI - CT of bronchial and bronchiolar diseases. AB - Computed tomography (CT) is useful in evaluating bronchial and bronchiolar abnormalities. Common bronchial and bronchiolar abnormalities include bronchiectasis, asthma, bronchial obstruction, and various forms of bronchiolitis. Causes of bronchiectasis include cystic fibrosis, childhood viral infection, allergic bronchopulmonary aspergillosis, and pulmonary fibrosis. On CT scans, cystic fibrosis may manifest with bronchial wall thickening, bronchiectasis (usually cylindrical, with varicose and cystic forms seen in advanced cases), and mucus plugs in the bronchi. Allergic bronchopulmonary aspergillosis is characterized by central, varicose or cystic bronchiectasis, predominantly in the upper lobes, with mucoid impaction in the bronchi. Traction bronchiectasis may be seen on CT scans of pulmonary fibrosis. Asthma is characterized by bronchial wall thickening due to inflammation. Bronchial dilatation and air trapping may also be seen. Bronchiolitis obliterans is manifested by direct and indirect signs on CT scans; the former consist of centrilobular branching structures and nodules, and the latter consist of bronchiectasis and bronchiolectasis, mosaic perfusion, and air trapping. CT findings of bronchiolitis obliterans organizing pneumonia (also known as cryptogenic organizing pneumonia) include air-space consolidation and nodules, with occasional bronchial dilatation and pleural effusions. PMID- 7991829 TI - [Doppler velocimetry: perinatal results according to an integral evaluation of resistances]. AB - The experience with 180 high-risk pregnancies evaluated with Doppler velocimetry in Rancagua Regional Hospital, classified according to an original integral resistance evaluation table, is presented. Perinatal outcome is analyzed in relation to this classification, demonstrating a high correlation between progressive increase of resistance and poor perinatal outcome, evidenced as proportion of SGA newborns, non-reactive NST, low five-minute Apgar score, admission to neonatology or perinatal death, with good sensibility, specificity and predictive values. PMID- 7991830 TI - [Hysterectomy by videolaparoscopy. Use of the CASH technique]. PMID- 7991831 TI - [Use of ultrasonic aspirator in surgery of breast neoplasms]. PMID- 7991832 TI - [Histological evaluation of cryosurgery in high grade intraepithelial neoplasia (CIN-III)] of the uterine cervix]. AB - Sixty patients, having high grade cervical intraepithelial neoplasia (CIN III) are analyzed. They are all treated primarily with cryosurgery followed, approximately 12 weeks thereafter, by cervical conization, in order to histologically evaluate the response to treatment. The mean follow up of the whole series was 36 months. Ninetieth five percentage of the patients were included in the series, having an abnormal PAP smear, suggesting presence of a CIN. Colposcopically directed biopsy prior to cryosurgery showed grade CIN III, with no glandular involvement in 61.7% of the cases. In 38.3% the endocervical glands were involved, cryotherapy was done in 60 patients, with single freezing in 26 (43.3%) and double freezing in 34 (53.7%) patients. On analyzing the cone specimen, 71.7% of the cases showed no residual disease. The group that received double freezing did better than the single one (79 versus 61%). As well, the group with out gland involvement did better than the group showing such condition (83.8 versus 52.2%). Cryosurgery is a good therapeutic modality in cases with CIN III, following street selection criteria and having a good and reliable follow up. PMID- 7991833 TI - [Metastatic carcinoma to the ovary of extragenital origin: analysis of 9 cases and review of the concept of Krukenberg's tumor]. AB - Between 1987 to 1992, nine patients with metastatic ovarian tumors of extragenital origin were analyzed. Seven corresponded to Krukenberg tumors, according to the traditional description of carcinoma with signet-ring cells and stroma with sarcomatoid reaction. The primary neoplasia was detected in 8 patients (89%) and corresponded to: gastric cancer (n = 4), colon cancer (n = 2), gallbladder cancer (n = 1) and breast cancer (n = 1). Mean survival in these patients was 11 months (range 4 to 20 months). Irrespective of their histology and origin, all the lesions were found to share similar macroscopic characteristics: bilateral enlarged ovaries, solid and embossed appearance. PMID- 7991834 TI - [Plasma estradiol levels and duration of lactation amenorrhea]. AB - In Temuco, Chile, 114 women in fully nursing, were studied, according to their length of lactational amenorrhea and their relation with estradiol levels at 3th postpartum month. Sixty six (58%) recovery their menses before the 6th postpartum month. The length of lactational amenorrhea was 100.7-5.2 and 277 +/- 10.6 days, for those mothers who were with menses and amenorrhea, respectively. The estradiol levels were 88 pmol/l higher in the woman with short length of lactational amenorrhea. This study corroborate, that short length of lactational amenorrhea is a condition highly frequent in Chilean population. The difference in the estradiol levels may be a indicators of the early recovery of the postpartum fertility. PMID- 7991835 TI - [Effect of arginine-vasopressin infusion on the secretion of tracheal fluid in sheep fetuses]. AB - Timely evacuation of alveolar fluid, release of surfactant and the beginning of continuous breathing, are key processes for an adequate adaptation of the fetus to the extrauterine life. Fetal vasopressin increases during labor and inhibit the secretion of tracheal fluid through a mechanism still unknown. The aim of this study was to elucidate the mechanism whereby vasopressin inhibit the secretion of lung fluid. We used fetal sheep chronically catheterized and infused either with vasopressin, vasopressin agonist (V2; dDAVP) or vasopressin antagonist (V1). Tracheal flow was measured during basal and infusions periods of 2 hours, monitoring fetal blood pressure, heart rate and blood pH and gases. Vasopressin and the V1 vasopressin antagonist caused a significant reduction in tracheal fluid flow, effect that was potentiated when both peptides were infused together. The V2 vasopressin agonist had no effect on the secretion of lung fluid. We concluded that vasopressin causes a significant inhibition of lung liquid secretion through a mechanism different to the activation of V1 and V2 receptors, and we propose the existence of other (s) kind of receptors (or receptors) for vasopressin that is (are) active during fetal life. PMID- 7991836 TI - [Effect of preoperative brachytherapy on estrogenic ovarian function, in patients with cervical neoplasms]. AB - Eight patients with cervical carcinoma, Stage I B, and tumor size of 5 centimeters or more were treated with preoperative brachytherapy followed by Wertheim; in all of them the right ovary was preserved. The minimum radiation rate over the ovary was 458 rads. Plasma estradiol and gonadotrophin levels were consistent with those observed after castration. These results are compared and discussed with those of the control group with only pelvic radiation or surgery. PMID- 7991837 TI - [Perimeters of the arm and the thorax as indicators of low birth weight]. AB - In a group of 317 newborns, measurements of the perimeter of the arm and the thorax were taken as an indicator of low birth weight. The perimeters of both the arm and the thorax had a high correlation with low birth weight (LBW) (0.88-0.80 respectively). In the sample group, the cut-off point to define low birth weight in the case of perimeter of the arm was 9 cm and was 29-30 cm for perimeter of the thorax. Applying these measurements facilitates early detection and treatment of low birth weight babies who are at risk for infant mortality in situations where it is not possible to weigh the baby at birth. PMID- 7991838 TI - [Impact of health care in the reduction of the mortality of cervix neoplasms in the health services]. AB - The importance of health care in the mortality caused by cervical uterine cancer in the age group 30 to 64 years is evaluated in the different health centers, excluding the effect of the quality or level of live in those areas. A model of multiple regression predicts the expected mortality rate according to the economic level of the population served by the health center. The different between the observed and predicted rates (the residual rate) is attributed to health care. Another multiple regression model with health variables checks the direct association between the magnitude of the residual rate and medical gynecological consultations; this variable is related significantly and positively to the number of consultations (patient visits) for general morbidity; specialities and with the numbers of midwives. The higher mortality rate associated with higher morbidity rate reflects defects in programs of early diagnosis and identified five deficitiary services. As the activities realized by midwives (such as prenatal check ups and gynecological consultation) are important and the lack of an inverse relation with the mortality rates shown, it is suggested that the resignation of activities and functions to strengthen secondary prevention of cervical uterine cancer be reviewed and modified. PMID- 7991839 TI - [Gyneco-obstetric aspects in women developing postpartum depression]. AB - The relationship between different variables was studied related to pregnancy, labor, puerperium, newborn and breast-feeding with the development of a depressive disorders during pregnancy, in a sample of 125 pregnant women. No relationship it's found with the presence of disease during the gestation period, except urinary tract infection. The same happens with other variable of labor, puerperium and newborn, Nevertheless, the major stress situations (urgent cesarean section, use of anesthesia during labor, diseases of the newborn, etc.) systematically present a higher incidence of depression. It is observer a relationship between the development of a depressive disorders and a decrease of the natural lactation period. PMID- 7991840 TI - [Effects of prenatal stress: an updated review]. PMID- 7991841 TI - [Cesarean section. Round table]. PMID- 7991842 TI - [Fetal death, 1-year prospective analysis]. AB - Fetal death (FD) over 22 weeks are analyzed during a one year period in a service with approximately 12,000 deliveries per year. 118 FD were found and the study was completed in 97 pregnancies (100 FD). A control group was included. The pathologies more related with FD were the premature rupture of membranes, chorioamnionitis and premature delivery. Followed by the funicular pathology, abruptio placentae, preeclampsia and intrahepatic cholestasia. Mother's educational level and prenatal care were clearly better in the control group. The majority of the FD occurred out of the hospital (70%). The anatomopathological study was performed in few cases (34%). We concluded that an important number of FD are preventable with an accurate prenatal care and that a complete and modern anatomopathological study including the placenta will decrease the high number (26%) of FD that remaining without diagnoses. PMID- 7991843 TI - [Transvaginal echography and endometrium in postmenopause]. AB - Thirty one postmenopause patients were studied, twenty three had metrorrhagia. They were examined by transvaginal ultrasonography with the purpose of measuring the depth of the endometrium. Endometrium depth < or = 10 mm is associated with minimal risk of endometrial cancer. The relationship between the echographic measurements and endometrium cancer, reveals a sensitive of 75%; specificity of 89%; positive predictive value of 60% and negative of 94%. PMID- 7991845 TI - [Prognostic factors in epithelial neoplasm of the ovary. A multivariate analysis]. AB - The results in the treatment of ovarian cancer in our center are analyzed from 1976 until 1989. Seventy nine patients have been treated. Patients were staged as by FIGO guidelines. Thirty three patients were staged as stage I, 9 as stage II, 26 as stage III and as stage IV. Median follow-up is 72 months with a minimum of 12. The actuarial survival was 93.8% for stage I, 36.3% stage II, 6.9% stage III 6.9% stage III and 9% in stage IV. The analysis of the prognostic factors was made by the Cox model. The clinical stage was the principal prognostic factor. No prognostic factors were found in stage I, II and IV but in stage III, complete surgery, well differentiated tumors and the possibility of rescue were of good prognosis. PMID- 7991844 TI - [Vesical filling for the management of umbilical cord prolapse]. AB - A new method for management of the umbilical cord prolapse is presented: the bladder of the patient is filled with 500 to 700 ml of saline solution through a catheter, the bladder produce the upward displacement of the fetal head and soon proceed to cesarean section, this method reduce the maternal risks and the perinatal mortality. Four case reports are presented with good results. PMID- 7991846 TI - [Microsurgical reconstruction of fallopian tubes]. AB - A six year study of 90 women with tuboperitoneal infertility at the Hospital Barros Luco-Trudeau is presented. 32.2% of them had tubal sterilization and had distal tubal occlusion. In 62.2% the peritoneal factor was present. In 40% distal microsurgery was done and in 32.2% proximal microsurgery was performed. The pregnancy rate was 48.8% in patients with adequate follow-up. The incidence of ectopic pregnancy was 9.5%. PMID- 7991847 TI - [Application of microsurgical principles of the reversal of tubal sterilization]. AB - The results in pregnancies obtained in sixty six patients recanalized using the microsurgical principles in a period of five years are presented. The pregnancy rate was 72.7% with 31 new borns (47%), 15 abortions (22.7%) and 2 ectopic pregnancies (3%). Using the life table the accumulative probability of pregnancies was 39%, 55%, 87% at 6, 12 and 24 months respectively. The results are statistically correlated with the parameters of age, time of sterilizations, technique of anastomosis and only or two Fallopian tubes reanastomosed. PMID- 7991848 TI - [Diagnosis of human papillomavirus infections in cervical cytology in the absence of classical signs]. AB - "Nonclassic" cytologic signs (NCS) of infection by human papillomavirus (HPV) were analyzed in two groups of patients: A: (condylomata) 81 women with both condylomata confirmed by biopsy and a cervical smear not showing the "classic" signs of HPV infection, and B: (controls) 50 cervical smears diagnosed as negative. In group A, 96% showed nuclear hyperchromatism, 78% showed perinuclear halos, 77% showed clear cytoplasm, and 74% showed mild koilocytosis. In 89% of the condylomata cases at least four NCS were found. In the control group only three cases showed nuclear hyperchromatism; the most frequent NCS in this group was perinuclear halo (50%). The frequency in which NCS of condylomata are found in smears without the classic signs is high. Nevertheless, 11% of these showed less than four NCS; in all of them, nuclear hyperchromatism was prominent. This is the most useful NCS in the diagnosis of HPV infection. PMID- 7991849 TI - [Borderline tumors of the ovary. Laparoscopic management?]. AB - Two cases of epithelial ovarian tumors of borderline malignancy initially approached by laparoscopy are presented. The role of laparoscopy are presented. The role of laparoscopy in the management of ovarian tumors is discussed. PMID- 7991850 TI - [Color Doppler hysterosalpingography. Preliminary experience]. AB - Tubal factor accounts for approximately 25% of the causes of infertility. The diagnosis has been made with x ray hysterosalpingography or laparoscopy chromoperfusion. We presents the utilization of ultrasonographic color Doppler flow used to perform hysterosalpingography to asses tubal patency. PMID- 7991851 TI - [Cytologic response of the irradiated vagina to estriol succinate]. AB - The vaginal response to estriol succinate was studied in 40 oncogynecological patients, 20 with irradiation (study group) and 20 without irradiation (control group). Both groups had artificial established menopause at the beginning of the treatment. The previous clinical and cytological patterns to estrogen therapy were more severe in the irradiated group; they presented the highest degree of vaginal atrophy which was related to the type and therapeutic dose used. Response of the study group to a continuous 4 mg of estriol as well as the control group, both has a positive effect in vaginal cytology and alleviates postmenopausal symptoms and improve the quality of life. PMID- 7991853 TI - [Ovarian hyperstimulation in women with fibrocystic mammary dysplasia treated with tamoxifen]. PMID- 7991852 TI - [Systematic echography in the first trimester of pregnancy]. AB - The purpose of this prospective study was to ascertain the usefulness of routine first trimester ultrasonography in 872 consecutive patients. A high incidence of abnormalities was noted: 35% A significant discrepancy between ultrasonography and menstrual dating was frequently noted: in 24% of all patients, and in 14% of patients with optimum menstrual history. These data suggest that routine obstetric ultrasonography should be considered for all patients at the first trimester, and that ultrasonometry in this period is the gold standard to estimate the true gestational age. PMID- 7991854 TI - [Pathology of the lower genital tract]. PMID- 7991855 TI - [Mycoplasma hominis and Ureaplasma urealyticum in pregnant and infertile women. Differences in tubal pathology]. AB - We studied the frequency of cervicovaginal bacteria in 47 pregnant women (16-41 weeks of gestational age), in 47 infertile patients and in 4 with gynecological diseases (not infections). When we compared the frequency of bacteria between pregnant and infertile women, we found that the biggest difference was with U. urealyticum. In fact the frequency of this germ was 61% in the total population studied, in pregnant women was of 72% which is statistically higher than the frequency in infertile women which was of 47% (p < 0.025). We think that the reason for the higher frequency of this germ is a consequence of the effect of estrogens that favors the proliferation of this of germ. In the case of M. hominis the frequency in pregnant women was of 13% and in infertile women was of 21% which was not statistically different. Within the group of infertile patients, those that had tubal damage had a higher frequency of germs that the patients that did not have damage, moreover M. Hominis was not detected in the infertile patients without tubal damage and in patients with tubal damage its frequency was of 25%. PMID- 7991856 TI - [Antenatal ultrasonic diagnosis of meconial peritonitis and follow up of newborn infants]. PMID- 7991857 TI - [Role of frozen section biopsy in the diagnosis of adnexal neoplasms]. AB - Three hundred and five patients undergoing exploratory laparotomy by adnexial tumors in our institution from January 1987 to October 1992 were studied. The results of the frozen sections vs permanent sections were compared. The diagnosis was concordant in 98.7% of the cases. Sensitivity was 96.9% and specificity was 99.6%. These results consagrate frozen sections as an accuracy and efficient intraoperative diagnostic form in the ovary tumoral pathology. PMID- 7991858 TI - [Gynecologic laparoscopic surgery. Clinical analysis]. AB - One hundred thirty six women received laparoscopy surgery. The majority were between 25 and 39 years old (86.8%) nuliparous (73.5%0). Six (4.4%) were under 19 and once over 40. The most common diagnosis (64%) and surgery (79.4%) was endometriosis. Other laparoscopic treatments were cystectomies (11.8%), ectopic pregnancy surgery (3.6%), and miomectomies (2.9%). PMID- 7991859 TI - [Transvaginal color Doppler in ovarian neoplasms]. AB - Thirty one patients with clinical and sonographic diagnosis of ovarian tumor were studied prospectively, with Transvaginal Color Doppler. There were 24 benign and 7 malignant tumors (4 stage I borderline, I stage IA cistoadenocarcinoma and 2 adenocarcinoma stage III). Six malignant tumors had resistance indexes (IR) from 0.17 to 0.55. In one borderline no vascular signal was obtained. The probability of malignancy increased inversely with the IR from 60%, with RI below 0.60 to 100% with IR below 0.4. PMID- 7991860 TI - [Atypical endometrial hyperplasia: characteristics of histopathological diagnosis in curettings]. AB - The frequency of Hendrickson's and Kurman's criteria for the diagnosis of endometrial carcinoma was analyzed in 25 cases of endometrial curettings in which the diagnosis of atypical hyperplasia was made. All cases had subsequent hysterectomies not showing carcinoma. Hendrickson's cytologic elements were found in 88% of the cases and architectural elements in 84% of the cases. Kurman's architectural elements were not found. In only one case stromal desmoplasia was present; 3 cases (12%) showed small cribes, all of them in tiny foci less than 0.5 mm. Small glands were present in 76% of the cases. Hendrickson's cytological and architectural criteria are not specific for carcinoma; they are frequently found in atypical hyperplasias. Kurman's criteria are absent in endometrial hyperplasias. Most cases of endometrial atypical hyperplasia do not show small cribes; when the latter are present, they are only focally found and measure less than 0.5 mm. PMID- 7991861 TI - [Uterine defibrillation in uterine inertia. Report of 2 cases]. AB - The uterine atony are the most common cause of postpartum hemorrhage. Manual compression and pharmacologic methods are usually used with a successful result. When pharmacologic methods fail to control hemorrhage from atony, surgical measures should be undertaken to arrest the bleeding before it becomes life threatening. We presents the utilization of electrical uterine defibrillation in two cases with acute hemorrhage confirming the effectivity of the proceeding. PMID- 7991862 TI - [Verrucous carcinoma in the cervix uteri. Report of a case]. AB - One observed case of verrucous carcinoma involving the uterine cervix is presented. Both clinical and pathologic aspects, and pertinent literature are discussed. PMID- 7991863 TI - [Advanced endometriosis treatment with leuprolide acetate]. AB - Endometriosis is a disease observed in women in fertile age, it causes pelvic pain characterized by dysmenorrea and dyspareunia. Moreover, there is an association with infertility. Between the alternative of the medical therapeutics of endometriosis drugs with hipogonadotrofic and hypoestrogenic effects, as the danazol and gestrinona has been used. At present, there are analogies of GnRH factor where leuprolide acetate allow a continue liberation in a monthly administration. This is a case of a woman with extensive endometriosis that has hepatitis due to danazol and subsequently was treated with leuprolide acetate. The effectiveness of leuprolide acetate is analyzed in relation with the relief of pain and the laparoscopic evaluation of the endometriosis focus. PMID- 7991865 TI - [Pre and post-graduate program in gyneco-obstetrics field of the North-American family physician]. AB - Description of the undergraduate program of the Department of Obstetrics and Gynecology, School of Medicine, Ohio State University, USA and the program of Family Medicine related to the speciality, in order to know the scope of family practice on this field. PMID- 7991864 TI - [Minimal deviation adenocarcinoma of the uterine cervix]. AB - A 33 year-old female with minimal deviation adenocarcinoma of the endocervix is presented. In two years five biopsies were needed to make the diagnosis. There was association with bilateral mucinous cystadenomas of the ovary. Even under radiotherapy and surgical resection the clinical outcome was fatal with 2 years of survival rate. The tumor shows fairly well differentiated endocervical glands which may be confused with different forms of endocervical hyperplasia but the clinical course is aggressive and fatal. PMID- 7991866 TI - [Advances in hormonal contraception]. PMID- 7991867 TI - [A re-evaluation laparotomy in ovarian neoplasms]. AB - "Second look" laparotomy in ovarian cancer demonstrated negative result in 49%, microscopic positive result in 17%, and macroscopic positive result in 34%. The prediction factors were related with, clinical stage, degree of differentiation and the postsurgical residual tumors after the first operation. PMID- 7991868 TI - [Colonic volvulus during pregnancy: 2 clinical cases]. AB - Two clinical cases of volvulus of the colon in pregnant women are presented. Both were operated on with success and the pregnancies continued without problems. PMID- 7991869 TI - [Simplified management of an in vitro fertilization program]. AB - The development of in vitro fertilization has accelerated in a dramatic way the understanding on gamete physiology. Results obtained with the technique are easily reproducible and consistent between different centers. It is well known that cumulative pregnancy rates with 5 or 6 cycles can reach up to 60% of couples being pregnant. However, the main limitations to successive attempts have been the cost of the procedure and the surgical transfer of the embryos. In an attempt to overcome this difficulties, efforts has been made to simplify the monitoring of induction of ovulation, use of GnRh analogs and non surgical transfers whenever it is possible. Results presented in 47 of these cycles show non significant differences, with data published elsewhere, on oocyte maturity, fertilization and cleavage rates. Moreover pregnancy rates per aspiration are 28.6% and per transfer 33.3%. We can conclude that ultrasonography alone to monitor ovulation induction as well as uterine transfers do not affect the outcome of the cycle. PMID- 7991870 TI - [Female genitoperitoneal tuberculosis an in force pathology]. AB - We present the experience during 1987-1991 years, about Female Genital Tuberculosis, at the University of Chile Clinical Hospital. We present 16 cases with histologic and bacteriologic demonstration; in two cases also positive cultures for myco bacterium tuberculosis. It is made emphasis about personal characteristics of patients physical examination findings, laboratories procedures and technics of diagnostic, treatment and posterior control of patients. We comments utility of new procedures as laparoscopy, gynecologic sonography and A.D.A. analysis of ascitis. PMID- 7991871 TI - [Intrauterine fluid collections as echographic findings in postmenopause]. AB - The possible relationship between the intrauterine accumulation of fluid during the peri and post-menopause period and genital cancer are studied by ultrasonography. In our experience 22% of the patients had endometrial cancer. PMID- 7991873 TI - [Hypocalciuria in pre-eclampsia]. AB - Recent studies have associated preeclampsia with hypocalciuria, nevertheless others do not show association. We proposed to determinate if this association exists, so we studied 25 term pregnancies patients (13 normotensives, 7 transient hypertension and 5 preeclamptic). We did not find significative differences in the hematocrit, serum calcium, serum creatinine, platelets count and the 24 hour diuresis between these groups. The serum uric acid was significative lower in the normotensive group (3.5 +/- 0.8 mg/dl) than in the preeclamptic group (4.9 +/- 0.89 mg/dl) (mean +/- SD) (p < 0.05). The 24 hour calciuria was lower in the preeclamptic group (121 +/- 78 mg/24 hours) than in the normotensive (256 +/- 71 mg/24 hours) and transient hypertension group (229 +/- 93 mg/24 hours) (p < 0.05). We measured the creatinine clearance and the fractional excretion of calcium in the transient hypertension and the preeclamptic groups, there was significative difference only in the fractional excretion of calcium (2.5 +/- 0.8% and 1.1 +/- 0.8% respectively) (p < 0.05). All the patients had a good clinical evolution, so the arterial pressure returned to normal values in a mean period within 7 days in both groups. There were 3 newborn who were small for gestational age (1 in the transient hypertension and 2 in the preeclamptic group). The difference we found in the 24 hour calciuria and the fractional excretion of calcium agree with the finds of other authors, further prospective studies are needed to understand the physiology and pathophysiology of calcium metabolism in normal, transient hypertension and preeclamptic pregnancy. PMID- 7991872 TI - [Importance of prolactin isoforms on ovary function in hyperprolactinemic women]. AB - Gel filtration chromatography in Sephadex G-100, was used to analyse the molecular heterogeneity of prolactin (PRL) in serum from seven hyperprolactinemic women. Chromatographic patterns from samples obtained from four women with hyperprolactinemia and normal menstrual cycles showed a predominance of big-big PRL (79%). In contrast, three women with hyperprolactinemia and amenorrhea presented a chromatographic pattern with predominance of little PRL (69%). The results suggest that the molecular heterogeneity of PRL found is associated with menstrual cycles disorders and hence with ovarian function. Normal ovarian function in hyperprolactinemic patients seems to be associated to increased levels of big-big PRL and altered ovarian function to high level of little PRL. PMID- 7991874 TI - [Gestational choriocarcinoma in a tubal pregnancy]. AB - We report a gestational choriocarcinoma arising in a tubal ectopic pregnancy. Unilateral salpingectomy and single agent methotrexate chemotherapy achieved a cure. A follow up of two years revealed no evidence of recurrence. PMID- 7991875 TI - [Potter syndrome caused by bilateral renal agenesis and duodenal atresia]. AB - A case of Potter syndrome secondary to renal agenesia and duodenal atresia with anular pancreas is presented. The karyotype was 47 XY-21. We discuss the antenatal diagnosis and the perinatal management. PMID- 7991876 TI - [Endocervical and endometrial atypical intestinal metaplasia, concomitant with leiomyosarcoma]. AB - One case of Intestinal Metaplasia with moderate Dysplasia of the cervix and endometrium associated to leiomyosarcoma is presented. Clinical and Anatomo Pathological aspects are reviewed. PMID- 7991877 TI - [Cesarean section]. PMID- 7991878 TI - Is farming good for your lungs? PMID- 7991879 TI - Corticosteroids and tuberculosis. AB - Common for all older studies is the use of less potent anti-tuberculosis chemotherapy as compared with the present. The results of these studies cannot without reservation be used in the present setting. The newer, prospective, randomized placebo-controlled trials include rather few patients and their number is limited. The results must be interpreted carefully. There is no reason to give prophylactic isoniazide treatment to Mantoux-positive patients or patients with earlier tuberculosis who start treatment with corticosteroids. If allergic reactions to one of the antituberculous drugs emerge during therapy, the treatment can, if necessary, be continued if corticosteroids are added. Pericardial tuberculosis and atelectasis in children with endobronchial tuberculosis should be treated with corticosteroids, as can pleural disease with prolonged fever and exudation. Cases of severe pulmonary tuberculosis may be treated with supplementary steroids. The effect seems modest. Patients with tuberculous meningitis, stages II and III seem to benefit from corticosteroid treatment. PMID- 7991880 TI - Arthropathy in cystic fibrosis. PMID- 7991881 TI - Prevalence of chronic obstructive pulmonary disease in elderly Finns. AB - The prevalence of chronic obstructive pulmonary disease (COPD) in the elderly is poorly known. The aim of this study was to determine the prevalence of COPD and to analyse the factors associated with it in an elderly Finnish population. The population consisted of persons resident in Lieto, Finland, born in or before 1926. One thousand one hundred and ninety-six individuals (488 men and 708 women, 93% of those eligible) participated in the survey, which was carried out in 1990 91 at the Lieto Health Centre. The methods included a nurse's interview and spirometry with a bronchodilator test. The participants were also clinically examined, and the number of subjects with COPD was determined using simple diagnostic criteria. Sixty-one men and 21 women with COPD were found. Thus the prevalence was 12.5% for the men and 3.0% for the women. In both sexes only about 2% of those who had never smoked suffered from COPD, but among the current smokers the prevalence was 35% for the men and 13% for the women. In a stratified analysis COPD was commonest among those with a low social status and histories of smoking and working in dusty occupations. In a majority the obstruction was only minimally reversible when tested with salbutamol inhalation. The study confirmed that the prevalence of COPD in the elderly with negative histories of smoking is low, and emphasizes the importance of reducing smoking as the only effective preventive measure. PMID- 7991883 TI - The annual risk of tuberculosis infection used as predictor of the future incidence of smear-positive cases. AB - It has been estimated that in underdeveloped countries every 1% annual risk of tuberculosis infection results in an incidence of 50 per 100,000 smear-positive cases. However, workers had theoretically speculated that the incidence would be about one-third less in countries with good medical facilities. I decided to test the latter theory in the city of Riyadh (capital of Saudi Arabia) which enjoys a high standard of living, easy access to medical facilities, and free treatment. I calculated the annual risk of infection (using the standard tables developed by the TSRU of the International Union Against Tuberculosis) from a nationwide survey of tuberculin reactivity that was conducted in 1987-1988. The annual risk was found to be 0.5% in the whole of Saudi Arabia as well as the city of Riyadh. Accordingly, the incidence of smear-positive cases should have been 25 per 100,000 in an underdeveloped community (0.5 x 50 = 25). However, the actual incidence of smear-positive cases in Riyadh was found to be only 15.2 per 100,000 in 1991-1992. This supports the theoretical speculation that the incidence, as predicted from annual risk of infection, is about one-third less in wealthy communities with adequate access to medical care. If this finding is confirmed, it could have two applications: First, the annual risk of infection could be used to predict the future incidence of smear-positive cases in high risk groups in wealthy countries, like immigrants from the third world, and foresee in advance what impact they will have on active tuberculosis.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7991882 TI - Tracheal wheezes during methacholine airway challenge (MAC) in workers exposed to occupational hazards. AB - Methacholine airway challenge (MAC) is a simple and useful means to assess bronchial hyperreactivity in workers exposed to various occupational hazards. Recently, wheeze detection by tracheal auscultation has been proposed as an indicator of bronchial responsiveness during bronchial provocation test in children. Our aim was to examine the relationship between the appearance of wheezes and the concurrent changes in forced expiratory volume in one second (FEV1) observed during MAC test in adults. Three cumulative doses of a methacholine solution (100 micrograms, 500 micrograms and 1500 micrograms) were inhaled by 45 workers with occupational exposure to flour dust. Spirometry was done using an electronic spirometer. Tracheal sounds were recorded with an electronic stethoscope placed over the anterior cervical triangle, 2 cm above the sternal notch. The amplified sounds were stored on magnetic tape, band-pass filtered (50-2000 Hz), and digitized at a sampling rate of 4096 Hz into a GenRad Vibration Control System. Wheezes were detected by fast Fourier transform (FFT) analysis and their presence compared to a 20% fall in FEV1. A positive MAC test by spirometry was found in 12 subjects whereas wheezes were identified in 14 subjects. Among the wheezing subjects, nine had a positive MAC test (range of fall in FEV1 = 20.6 to 42.3%) and five had a negative one (range of fall in FEV1 = 3.6 to 16.9%). Moreover, no wheezes were found in the remaining three subjects with a positive MAC test (range of fall in FEV1 = 20.7 to 27.4%). Taking a 20% fall in FEV1 as reference, wheezes were 75% sensitive and 84.8% specific to detect airflow obstruction. In conclusion, since it carries a significant although small false-negative rate, the acoustic technique based upon wheeze detection cannot, at the present time, fully replace spirometry during airway challenge testing in subjects with suspected asthma. PMID- 7991884 TI - Endobronchial tuberculosis: diagnostic features and therapeutic outcome. AB - BACKGROUND: Endobronchial tuberculosis (EBTB) is not seen often in the adult population. In most cases it is associated with pulmonary tuberculosis. During its course significant tracheobronchial stenosis may develop. In this study we report our experience with patients with EBTB. METHODS: The records of 38 patients in whom EBTB had been proved by fibre optic bronchoscopy, microbiology and histology studies were evaluated. RESULTS: Symptoms were non-specific and represented mainly the co-existing pulmonary tuberculosis. Signs characteristic of airway obstruction were rare (localized wheezing in 6%). Indications for bronchoscopy were radiographic features (87%), microscopy smear negatives (8%), wheezing (3%), and blood stained sputum (3%). The lesions were more likely to be seen in the main and upper bronchi. In 5% of patients the lower trachea was involved. Most lesions looked inflamed (51%), followed by caseous (19%), granulomatous (17%), ulcerative (12%), and fibrotic appearance (1%). The degree of stenosis was nil (22%), minor (45%), significant (13%), subtotal (13%), or total (7%). The patients were treated with a combination of antituberculosis drugs. Four patients underwent surgical procedures. Dilatation techniques were used in two patients for a right and left main bronchus stenosis respectively, with significant improvement in one. Dilatation in combination with laser therapy of a right intermediate bronchus stenosis did not result in re-expansion of the dependent part of the lung due to pleural adhesions. Left pneumonectomy was performed in one patient for destroyed lung. Twenty-two patients agreed to follow up bronchoscopy. The macroscopic appearance of the mucosa had improved in most cases but the degree of stenoses was unchanged in a considerable proportion (58%). Bronchial stenosis in one patient subsided during therapy but developed again at a later stage. CONCLUSIONS: Patients with pulmonary tuberculosis and radiographic evidence of volume loss are recommended to undergo bronchoscopy to rule out EBTB. Specific symptoms for EBTB are rare. Biopsy of inflamed areas of bronchial mucosa seems to be indicated. Despite adequate antituberculosis therapy tracheobronchial stenosis may develop. Long term follow up including bronchoscopy seems therefore advocated. Dilatational intervention may be indicated in selected cases. PMID- 7991885 TI - The efficacy and tolerability of inhaled salmeterol and individually dose titrated, sustained-release theophylline in patients with reversible airways disease. AB - In a double-blind, double-dummy, cross-over, multicentre study, 141 patients with moderate reversible airways disease were randomized to receive either 50 micrograms salmeterol via a metered dose inhaler or individually dose-titrated oral theophylline, both twice daily for a 2-week period. Just over half (n = 77) the patients had received theophylline before, but 64 patients were new to theophylline therapy. Efficacy was based on lung function data and symptom scores. Salmeterol produced significantly higher increase in mean morning peak expiratory flow (PEF) of 161 min-1 (P < 0.001; 95% Confidence Interval (CI); 8 241 min-1) and mean evening PEF of 151 min-1 (p < 0.001; 95% CI; 7-221 min-1) compared with theophylline therapy. Further analysis of the data revealed that the increase in PEF with salmeterol compared with theophylline was highest in a sub-group of patients new to theophylline therapy. Patients on salmeterol had significantly less night-time awakenings than those on theophylline (P = 0.011) and significantly less daytime symptoms (P = 0.017). There was also a significant increase in the number of nights (P = 0.013) and days (P < 0.001) on salmeterol when no additional salbutamol was required compared with theophylline. Theophylline produced a higher incidence of adverse events compared with salmeterol. The results of this study show that inhaled salmeterol is more effective and better tolerated than individually dose-titrated oral theophylline over a 2-week study period in patients with moderate asthma. PMID- 7991886 TI - Miliary tuberculosis in Edinburgh--a comparison between 1984-1992 and 1954-1967. AB - We have reviewed the records of 29 patients notified with miliary tuberculosis in Edinburgh from 1984 to 1992 and compared our findings with those for the 40 patients previously reported in Edinburgh from 1954 to 1967. The incidence of miliary tuberculosis has not changed. Respiratory symptoms of cough and dyspnoea were commoner in 1984-1992 (P < 0.001) perhaps reflecting the increase in mean age at presentation (73.5 vs. 59.4 years; P < 0.001). Mortality was 50% in 1984 1992, significantly higher (P < 0.05) than the 25% recorded in 1954-1967. Forty percent of cases in both time periods were of cryptic miliary disease. The diagnosis of cryptic disease tended to be made more often post-mortem and less often by a trial of anti-tuberculosis chemotherapy in 1984-1992. Our findings emphasize the current poor outcome associated with a diagnosis of miliary tuberculosis. It is important to consider this diagnosis in elderly patients with unexplained pyrexia and implement a trial of specific anti-tuberculosis chemotherapy to confirm it. PMID- 7991887 TI - Serum eosinophil cationic protein (ECP) in chronic asthma. Relationship to spirometry, flow-volume curves, PC20, and exacerbations. AB - Serum ECP was measured in a double-blind study in relation to spirometry, flow volume curves, and histamine PC20 (30-s tidal breathing method, normal value > 32 mg ml-1) in 20 chronic asthmatic patients (five male), mean age 48.9 yr (SD 11.0), once a month and at additional visits due to acute exacerbations over a 6 month period. All patients were on maintenance inhaled corticosteroid therapy. Serum ECP was considered elevated at > or = 20 micrograms l-1. ECP showed significant negative correlations with lung function, especially when ECP was elevated (45/143 observations): r = -0.48, -0.48, and -0.49 for respectively FEV1, PEF, and MMEF (all at baseline and as % predicted, P = 0.001), the best correlation being with FEV1/FVC ratio (r = -0.61, P < 0.001). PC20 only had a weak overall correlation with ECP (r = -0.21, P = 0.015). Eosinophilia at > or = 0.400 x 10(9) cells l-1 (38/143 observations) did not show any significant correlations with the lung function variables. The patients were subdivided into three groups according to exacerbations. Group A consisted of seven patients with suspected infectious exacerbations (mean 1.4), group B of six patients with suspected inflammatory exacerbations (mean 3.2), and group C of seven patients who did not experience any symptomatic exacerbations. A significant difference in mean ECP was found between group B and A (33.1 vs. 10.2, P = 0.003). Group B also differed significantly from group A with respect to lung function and PC20, but not to atopy, lung function and PC20 being lower and variability higher in group B. The findings of this study suggest that serum ECP is a sensitive marker of inflammatory airflow obstruction in chronic asthma. Elevated ECP seems to denote patients at risk from inflammatory exacerbations, resulting in practical implications for the therapeutic management of chronic asthma. PMID- 7991888 TI - Comparison of fibre optic bronchoscopy histology in an unselected series of patients. PMID- 7991889 TI - Resolution of superior vena cava obstruction following thrombolytic therapy in a patient with cystic fibrosis and a long-term indwelling catheter. PMID- 7991890 TI - Risk of needle track metastasis after fine needle lung aspiration in lung cancer- a case report. PMID- 7991891 TI - Vocal cord paralysis as the presenting symptom of sarcoidosis. PMID- 7991892 TI - [Gumboro disease (infectious bursitis) in Madagascar]. AB - Four Gumboro disease (IBD) outbreaks were identified between February and June 1993 in the Antananarivo area (Madagascar) exhibiting the largest commercial poultry production activity. Affected birds were 3 to 5 weeks old, the mortality rate ranged from 5.70 to 27.4%. Typical symptoms and gross lesions were observed, necrotic degeneration of bursal follicles was also detected. By means of agar immunodiffusion test, IBD viral antigen was demonstrated. Since the IBD has never been recorded in the country before, the probability of an external origin through the importation of day-old chicks is high. PMID- 7991893 TI - [First case of an outbreak of hemorrhagic septicemia caused by Pasteurella multocida serotype B6 in northern Cameroon]. AB - For the first time in Cameroon, a strain of Pasteurella multocida serotype B6 was isolated from a haemorrhagic septicaemia outbreak in Zebu cattle in the area of Maga (Far Northern Province). Through the mouse protection test, evidence was given that there was no cross protection between this strain and the strain of Pasteurella multocida serotype E6 which is used as an inactivated vaccine in Cameroon. Hence, it is recommended to use a combined vaccine including both serotypes for the Central and West African countries. PMID- 7991894 TI - [Ancient methods of surveillance and control of rinderpest]. AB - Using the many documents available on the history of rinderpest, it is possible to accurately describe the practical measures adopted for rinderpest surveillance and control from Antiquity to the 19th Century. Surveillance was based on clinical diagnosis, post-mortem examination, animal inoculation, and also on the knowledge of the conditions under which infection occurred: aetiology, pathogenesis, susceptible species, virulent material, mode of infection, incubation period, etc. The historical facts are assembled and compared, with comments on each of these points. Control was based upon the application of general disease control measures, attempts at vaccination, and treatment. A study of these procedures makes it possible to compare their efficacy and describe the major steps of their implementation. PMID- 7991895 TI - [First case of adenomatosis in a ewe in Tunisia]. AB - The authors describe a typical case of adenomatosis in association with parasitic lesions in a ewe. They show the importance of histological data in the diagnosis of this disease and confirm its presence in Tunisia. PMID- 7991896 TI - [Evaluation of the vaccinal protection against rinderpest in Cameroon. I. Province of Adamaoua]. AB - As a part of the panafrican rinderpest campaign, a serological survey of 5,720 samples was undertaken in the Adamaoua province of Cameroon. The herd immunity level varied from 60 to 73% in the four departments investigated. Vaccination of all animals from the age of six months, replacement of vaccination equipment, restoration of crushes, and use of magnesium sulfate, or as a substitute, saline for lyophilized vaccine reconstitution are recommended. PMID- 7991897 TI - [Ticks and hemoparasitoses of livestock in Senegal. VI. The Soudano-Sahelian zone]. AB - The authors report the results of a study on ticks and hemoparasitoses among cattle, sheep and goats in the Sudano-Sahelian zone. During a period of 15 months, ticks were systematically removed from 40 cattle, 40 sheep and 40 goats in order to assess the population dynamics and determine more accurately the preferential sites of settlement of the different species. The following species were collected in ruminants: Hyalomma truncatum, H. marginatum rufipes, Rhipicephalus evertsi evertsi, Rh. guilhoni, Amblyomma variegatum, Boophilus decoloratus. Concurrently, studies were made on hemoparasitoses using blood smears and splenectomy. The following species were found in cattle: Anaplasma marginale, Ehrlichia bovis, Theileria mutans. Infections detected in sheep and goats were caused by Anaplasma ovis, Ehrlichia ovina and Theileria ovis. The PCV values of apparently healthy nature animals as well as the seasonal variations in this hematological parameter were investigated. PMID- 7991898 TI - [Subcutaneous nodules and cutaneous lesions caused by different Onchocerca in African cattle]. AB - Subcutaneous nodules and skin biopsy specimens obtained from the umbilical area of 6 onchocercal Bos indicus were collected in Cameroon and subjected to a histological examination. The nodules containing Onchocerca ochengi and Onchocerca dukei showed the same structure as Onchocerca volvulus nodules in man; they consisted of inflammatory pseudo-cysts often containing a female filaria. These pseudo-cysts were classified as "young", "active" and "old" depending on the inflammatory cellular component of their walls. The nodules were surrounded by a connective tissue capsule criss-crossed by vessels containing sections of microfilariae and morula in the vascular lumen. The skin, infected with microfilariae of these two species, of O. gutturosa and O. armillata, showed various dermatitis lesions with fibrosis, similar to those observed in patients with onchocerciasis. In most cases, inflammatory infiltrates surrounded the lymphatic capillaries along the blood vessels, giving rise to lymphangitis. The presence of microfilariae inside the granulomatous tissue demonstrates that microfilariae were deposited directly into the cystic lumen. Only the microfilariae which escaped the inflammatory reaction were able to penetrate the lymphatic vessels. They could then migrate into the lymphatic system and reach the superficial layer of the dermis. Bovine nodular onchocercomata represent an interesting model for human onchocerciasis. PMID- 7991899 TI - Haematological changes in ewes experimentally infected with Trypanosoma brucei. AB - Changes in the haematological values were studied in West African Dwarf ewes infected with Trypanosoma brucei. This disease was characterized by a normocytic normochromic anaemia in the acute phase and a severe macrocytosis during the chronicity. The observed changes suggest inadequate erythropoiesis in the acute phase while the chronic phase had a superior but still inadequate erythropoietic response with persistent anaemia. Normal total leucocyte values were observed during the acute phase while leucocytosis was a permanent feature in the chronic phase. PMID- 7991900 TI - [Camel trypanosomiasis caused by Trypanosoma evansi (Steel 1885), Balbiani 1888, in Islamic Republic of Mauritania: results of surveys in the Trarza region]. AB - A first survey concerning camel trypanosomiasis due to Trypanosoma evansi was carried out in the Trarza region (south-western Mauritania). Blood smears were made from 218 animals and 160 were submitted to an indirect immunofluorescence test. Young calves below one year old seem to be free of T. evansi infection, while in dairy females, average rates of infection of 7.3% (blood smears) and 24.5% (serological results) were found. The type of herd management seems to be an important risk factor: the herds that frequent, even temporarily, the wooded areas of the Senegal river valley or permanent water collections (R'kiz lake) show the highest infection rates. Recommendations are presented to camel rearing owners, especially those with dairy camel herds in the South of the country. PMID- 7991901 TI - [Pharmacokinetics and plasma protein binding of sulfamethoxypyridazine in camels (Camelus dromedarius)]. AB - The pharmacokinetics of sulfamethoxypyridazine (SMPD) were investigated in the camel after intravenous and oral administration. After intravenous injection, the plasma concentration of the drug followed the kinetics of a two-compartment model. The steady-state volume of distribution (Vss) of 0.47 l/kg suggested that sulfamethoxypyridazine was mostly distributed within the vascular compartment and the strongly vascularized tissues. The elimination from the body was rather slow, with a biological half-life [t1/2(beta)] and a total plasma clearance of about 9.5 h and 0.037 l/kg.h, respectively. Oral treatment showed that the maximum plasma concentration was reached 17 hours post drug administration and that the bioavailability ranged around 57%. Study of the plasma protein binding showed that the percentage of SMPD binding to plasma proteins varied from 47 to 72% and seemed to be concentration-dependent. The total binding capacity and the dissociation constant at equilibrium were 196 micrograms/ml and 335 micrograms/ml, respectively. PMID- 7991902 TI - [Postoperative cognitive dysfunction and its value for anesthesiologists]. PMID- 7991903 TI - [Postoperative mental confusion in the elderly with hip fracture. Perioperative risk factors]. AB - OBJECTIVE: To determine the incidence of postoperative mental confusion and perioperative risk factors in elderly patients with femoral neck fractures. PATIENTS AND METHODS: A prospective study of patients 65 years of age or older undergoing surgery for hip fracture with intradural anesthesia between March 1992 and August 1993. Although the total number of cases came to 162, only 50 patients were enrolled in the study: the rest were excluded mainly because of mental deficits presenting before surgery. Folstein's Mini-Mental State test was used to assess mental function. Risk factors analyzed were classified as preoperative, intraoperative (in the operating room and the recovery room) or postoperative (hospital ward). RESULTS: Eleven (22%) patients showed signs of postoperative mental confusion. Simple analysis revealed a correlation between mental confusion and ASA (p = 0.01), neuropsychiatric history (p = 0.03) and preoperative hemoglobulin, red blood cell and urea nitrogen levels (p = 0.02). Multifactorial discriminant analysis indicated that patients with low red cell counts before surgery, high urea nitrogen and neuropsychiatric histories were more predisposed (p = 0.004) to mental confusion. CONCLUSIONS: A high incidence of postoperative mental confusion is associated to pre-surgical factors. We therefore suggest that greater preventive and therapeutic efforts be directed preferably to preparation before surgery, especially in patients at high risk. PMID- 7991904 TI - [Adenosine triphosphate in the peroperative management of hypertensive crises and heart rate disorders in the surgical treatment of pheochromocytoma]. AB - OBJECTIVE: To assess the hypotensive and antiarrhythmic effect of adenosine triphosphate (ATP) and its impact on hypertensive crises and heart rhythm abnormalities resulting from surgery to remove pheochromocytoma. PATIENTS AND METHODS: A prospective study of 7 patients with pheocromocytoma who were scheduled for unilateral (4) or bilateral (3) suprarenalectomy prior to treatment with phenoxybenzamine and propranolol. The anesthetic procedure was the same for all patients, as was monitoring: ECG, digital pulse oximetry, capnography, direct recording of arterial pressure by a catheter in the left radial artery and a Swan Ganz fiber optic catheter in the pulmonary artery to measure pulmonary pressures and mixed venous oxygen saturation. Minute volume was measured by thermodilution. Blood glucose levels and urine excreted through a catheter were recorded hourly during surgery. During surgery, when arterial pressure had risen 20% above baseline level, i.v. infusion of ATP 0.5 mg/kg/min was begun and adjusted up or down depending on patient response. Infusion was stopped when the suprarenal vein had been tied. Hemodynamic analysis was performed during 4 phases: 1) start of surgery; 2) during manipulation of the tumor; 3) after excision, and 4) after surgery. Hemodynamic and metabolic variables were recorded, as were ATP doses and requirements for vasopressors and antiarrhythmic drugs. RESULTS: We found the following changes between phase 1 and phase 2, coinciding with ATP infusion: systemic arterial pressure increased 22.2%, heart rate increased 28.04% (with no cardiac arrhythmia observed in any patient), pulmonary artery pressure rose 25.35%, pulmonary capillary pressure rose 22.17%, cardiac index rose 108% while systemic vascular resistance decreased 55.82% and pulmonary vascular resistance decreased 33.96%.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7991905 TI - [Comparative study of intravenous anesthesia with propofol in continuous perfusion and neuroleptanalgesia in traumatology surgery]. AB - OBJECTIVE. To study propofol as the single agent for both anesthetic induction and maintenance with respect to quality of anesthesia, hemodynamic effects, quality of recovery and analgesic requirements in comparison with neuroleptoanesthesia as the technique of reference. PATIENTS AND METHODS. We selected 2 homogeneous groups of 15 ASA I-III patients undergoing traumatological surgery. Patients were premedicated with bromazepam 3 mg p.o. and droperidol 0.03 mg/kg prior to induction. Induction was achieved with propofol 1.5-2.5 mg/kg in group I (GI) and with sodium thiopental 4-5 mg/kg in group II (GII). Maintenance was by continuous infusion of propofol 6-12 mg/kg in GI and with droperidol 0.15 microgram/kg/h and 50% N2O/O2 in GII. Both groups received fentanyl 4 micrograms/kg/h. Neither analgesia nor curarization were antagonized pharmacologically. Variables recorded were time and quality of anesthetic induction, mean duration of anesthesia, anesthetic education time, time until orientation and time of residual analgesia. Hemodynamic parameters were recorded for both groups at baseline, after induction, at intubation, at 2 and 5 min after intubation, at the start of surgical incision, 30 min after start of incision, and at the end of surgery. Results for the two groups were compared, as were results at the various moments of measurement within groups. PMID- 7991906 TI - [Stress among anesthesiologists in the city of Havana]. AB - OBJECTIVE: To determine whether or not anesthesiologists are more vulnerable to stress, and whether or not they suffer related psychosomatic symptoms. MATERIAL AND METHOD: Representative samples of 50 anesthesiologists and 80 other physicians not members of surgical teams in Havana, taken from a stratified randomized sample population. Data on the subjects' vulnerability to stress, anxiety levels and symptoms were collected through psychological testing and questionnaires. RESULTS: Data obtained were subjected to statistical analysis, showing that susceptibility to stress was higher among anesthesiologists (64%) than in the control group (40%). Stress levels were also higher among anesthesiologists (60%) than among the controls (43%) and psychosomatic symptoms were highly related. CONCLUSION: Anesthesiologists are subjected to stress that leads to psychosomatic symptoms to a greater extent than are other physicians. PMID- 7991907 TI - [Influence of anesthetic technique in postoperative analgesia in thoracic surgery]. AB - OBJECTIVE: To compare the intensity of postoperative pain after thoracotomy with 2 anesthetic techniques: 1) thoracic epidural block with bupivacaine administered before surgery (combined anesthesia with isoflurane) and 2) conventional balanced anesthesia with isoflurane and endovenous fentanyl. PATIENTS AND METHODS: Thirty patients scheduled for thoracotomy by lateral incision (T5-T6) were randomly divided into 2 groups of 15. Group A received 8 ml of 0.5% bupivacaine with adrenalin 1:200.000 30 min before start of surgery while group B received 8 ml saline solution through an epidural catheter inserted to T4-T8. Combined anesthesia (4 ml 0.5% bupivacaine through an epidural catheter 150 min after the first dose and isoflurane in 100% oxygen) was used in group A. Group B received balanced anesthesia with endovenous fentanyl 2.5 micrograms/kg and isoflurane in 100% oxygen. The difference in pain intensity during postoperative recovery was assessed by way of the following variables: number of boluses administered by epidural patient-controlled analgesia (bupivacaine 0.0625% and fentanyl 6 micrograms/ml); score on a visual analog scale of 10 at baseline and at 1, 3, 7, 11, 19 and 43 hours after surgery; and need for additional analgesia (diclofenac) during the 43 hours of study. Arterial gases were measured during the preoperative period and at 1, 3, 7, 19 and 43 hours after surgery. RESULTS: No significant differences in pain intensity measured on the visual analog scale, by the number of boluses per patients or by need for additional analgesia were found between the 2 groups. The total number of boluses administered and additional analgesic requirements were greater in the group receiving bupivacaine, although the difference was not significant (p = 0.095 and p = 0.056, respectively). Nor were there significant differences in pH and PaCO2 levels for the 2 groups. CONCLUSIONS: Analgesic efficacy after thoracotomy was similar for our 2 groups receiving either combined anesthesia (epidural bupivacaine at 0.5% and isoflurane) or balanced anesthesia with isoflurane and endovenous fentanyl. PMID- 7991908 TI - [Nuclear magnetic resonance and anesthesia]. AB - Anesthesia for imaging by nuclear magnetic resonance presents special problems due to the effect of the large magnetic field and high frequency radio waves on monitoring and respiratory systems. These systems in turn affect image quality. Special materials should be designed specifically for this context or existing materials should be modified. PMID- 7991909 TI - [Treatment with sympathetic intravenous block with reserpine in work-related reflex sympathetic dystrophy]. AB - To assess the results obtained in treatment of sympathetic reflex dystrophy by sympathetic endovenous blockades with reserpine in working patients. We reviewed 170 diagnoses of sympathetic reflex dystrophy in 165 patients. One hundred seven were located in the foot, 13 were in the knee and 50 were in the hand. All were treated once a week for 3 weeks with local sympathetic endovenous blocks with reserpine (1 mg in the upper extremity and 1.5 mg in the lower extremity). We analyzed the location, etiology, course, X-rays, gammagrams, psychological state, other treatments, associated conditions, number of blocks received and side effects. The results were classified as excellent, good, fair and nil. We particularly reviewed sympathetic reflex dystrophy associated to Colles' fractures. Five hundred forty endovenous sympathetic blocks with reserpine were performed. Results obtained were excellent in 57 (34%) patients, good in 77 (45%), fair in 29 (17%) and nil in 7 (4%). Sympathetic reflex dystrophy leads to loss of 215 +/- 91 working days. In patients with Colles' fracture without sympathetic reflex dystrophy the loss is 96 +/- 31 days, although this period lengthens to 115 +/- 15 days if the two conditions are associated in stage I and to loss of 193 +/- 71 days if the association is in stage II. Results of treating sympathetic reflex dystrophy with sympathetic endovenous blocks with reserpine are satisfactory, particularly when diagnosis and treatment are early, clearly demonstrating the usefulness of this technique in workplace medicine. PMID- 7991910 TI - [Total intravenous anesthesia in general surgery]. AB - To evaluate unwanted side effects expressed in hemodynamic parameters, postanesthetic recovery and quality of intravenous total anesthesia (IVTA) with propofol, fentanyl and atracurium. A prospective study in 292 patients undergoing general surgery. Fifty-three percent of the patients were ASA I, 32.2% were ASA II and 14.8% were ASA II, representing a wide range of ages, weights and heights. Mean time of anesthesia was 108.25 +/- 56.96 min. Anesthesia was achieved with propofol 0.108 +/- 0.027 mg/kg/min, fentanyl 0.093 +/- 0.035 microgram/kg/min and atracurium 0.011 +/- 0.0034 mg/kg/min. Slight pain was evident at injection in 1.7% of the patients. Greater hemodynamic instability was recorded at induction, with mean decreases in systolic and diastolic arterial pressures of 16% and 10%, respectively, with scarcely any response to intubation and extubation. Anesthetic recovery was recorded at 5.95 +/- 4.97 min, with surgical amnesia in 100% of the patients. Nausea was seen in 3.42% and vomiting in 1.7%. Patient evaluation of anesthetic technique was "good" in 60.3% and "excellent" in 39.7%. Propofol dose was significantly (p < 0.05) correlated with age (r = -0.33) and time of anesthesia (r = -0.4). IVTA with propofol and fentanyl in general surgery provides adequate maintenance of anesthesia for surgery and recovery, with good hemodynamic stability. In older patients and longer times of anesthesia, the total dose of propofol administered decreases, with negative effect on time and quality of recovery. Total dose of propofol administered is not significantly correlated with either time or quality of recovery. PMID- 7991911 TI - [Spinal block in pediatric anesthesia (II)]. PMID- 7991912 TI - [Heart blockade and reversible ventricular asystole after propofol administration]. PMID- 7991913 TI - [The use of laryngeal mask in cricoidoarytenoid arthritis]. PMID- 7991914 TI - [Anesthetic risk and the education of resident physicians]. PMID- 7991915 TI - [Myotubular myopathy (centronuclear) and expected difficult intubation. Anesthetic management]. PMID- 7991916 TI - [The treatment of asymptomatic ventricular dysfunction with angiotensin converting enzyme inhibitors]. PMID- 7991917 TI - [Current epidemiological information on cardiovascular diseases in Spain. The usefulness of national registries in cardiology]. PMID- 7991918 TI - [The incidence, mechanisms and clinical factors predictive of sudden death in patients with severe heart failure evaluated in anticipation of heart transplantation]. AB - INTRODUCTION AND OBJECTIVES: Sudden death is not uncommon in patients with severe congestive heart failure. The aim of our study was to assess the incidence, mechanisms and clinical predictors of sudden death in a large series of patients with severe congestive heart failure evaluated for heart transplantation. METHODS: With this aim we have reviewed our experience on 240 consecutive patients with severe heart failure studied in our hospital from May 1986 to June 1992. Heart failure was due to ischemic heart disease in 35% of patients and idiopathic dilated cardiomyopathy in 65%. Age was 47 +/- 12 years, left ventricular ejection fraction was 20 +/- 6%, and symptom class was IV in 88% of patients and III in 12%. RESULTS: Sixty-eight of the 240 patients (28%) died without transplantation. Death was sudden in 21 patients (31% of deaths, and 9% of all patients), due to heart failure in 41 (68%), and due to malignancy (ampuloma) in 1 (1%). Mechanism of sudden death could be identified in 12 cases: ventricular tachycardia/fibrillation in 8 and bradycardia/electromechanical dissociation in 4. On multivariate analysis (stepwise logistic regression), a lower tolerated captopril dosage (p = 0.004), a lower systolic blood pressure (p = 0.079) and a history of a ventricular tachycardia/fibrillation (p = 0.073) were independent predictors of sudden death. CONCLUSIONS: It seems possible to identify, between patients with severe heart failure, a subgroup of patients at higher risk for sudden death by means of such simple clinical parameters. PMID- 7991919 TI - [The safety of the treatment of an acute myocardial infarct by immediate intravenous fibrinolysis in the regional hospital environment]. AB - INTRODUCTION AND OBJECTIVES: Our aim was to evaluate the utility of thrombolytic therapy administered outside tertiary hospital. METHODS: We analyzed 80 consecutive patients with acute myocardial infarction admitted to the emergency area of primary hospital within 24 hours after the onset of symptoms and lastly transported to a coronary care unit (CCU) of a reference hospital. The thrombolytic protocol was performed by medicine department of primary hospital and the CCU of reference hospital. RESULTS: 23 patients without (group A) and 57 with (group B) fibrinolytic therapy (APSAC 50 patients and streptokinase 7 patients) were analyzed. Group A patient were older (mean: 67 +/- 11 vs mean: 62 +/- 10 years; p = 0.01), and arrived later to emergency area (mean 254 +/- 284 vs mean 163 SD 161 min; p = 0.04) and to the coronary care unit (mean 561 +/- 371 vs mean 334 +/- 177 min; p = 0.0002). The guard physician decision to start or not the fibrinolytic therapy, was adequate in 86% of the patients (sensitivity 87%, predictive positive value 95%, specificity 83%). Complications on emergency area or during transport in group B were ventricular fibrillation in 9%, AV block (2-3 degree) in 9%, severe nonsustained ventricular arrhythmia in 11% and transitory hypotension in 23%. No death occurred before CCU admission. In group B, 35% patients was treated within the first 2 hours. The average time gain was 124 min (thrombolysis administration--CCU admission). CONCLUSION: On emergency area of primary hospital, thrombolytic therapy is feasible and safe when administered by well-equipped and well-trained medical emergence area and ambulance staff. PMID- 7991920 TI - [The usefulness of transesophageal echocardiography in the diagnosis of infectious endocarditis and its complications]. AB - INTRODUCTION AND AIMS: Transthoracic echocardiography is a technique with high specificity but low sensitivity in the diagnosis of valvular vegetations and infectious endocarditis complications. Recent reports have shown the transesophageal technique to be more sensitive. The aim of this study was to assess the comparative diagnostic roles of transthoracic and transesophageal echocardiography in infectious endocarditis. METHODS: Eighty-eight patients with infectious endocarditis (native valve in 71 and prosthesis in 17) were studied. All underwent transthoracic echocardiogram followed by transesophageal study to detect vegetations and possible complications, particularly paravalvular abscesses. RESULTS: Transthoracic echocardiogram diagnosed vegetations in 33 (46%) of the 71 native valve endocarditis, whereas these were detected by transesophageal study in 67 (94%). In 23 patients vegetations were surgically confirmed. Transthoracic echocardiography failed to diagnose vegetations in any of the prosthetic endocarditis, whereas they were detected by transesophageal study in 11 of the 17 cases (65%). Of the 9 patients who underwent surgery in the acute phase, 5 presented vegetations on transesophageal study which were confirmed at surgery. Transesophageal echocardiography diagnosed 14 abscesses: 11 aortic peri-annular and 3 in the interfibrous. Echocardiography only detected 1 of the peri-annular aortic abscesses. All patients with peri-annular abscess underwent surgery. Transesophageal echocardiography was also more effective than transthoracic in the diagnosis of other complications: 15 vs 4 chordae tendineae mitral valve rupture and 18 vs 13 aortic valve disruption. CONCLUSIONS: Transesophageal echocardiography is more effective than transthoracic echocardiography in the diagnosis of infectious endocarditis and its complications and would therefore be indicated in all cases of absence of vegetations on transthoracic echocardiography and clinical suspicion of endocarditis. Transesophageal echocardiography could be indicated in all cases of clinically suspected aortic endocarditis to rule out peri-annular abscesses. PMID- 7991921 TI - [Cardiac surgery in patients over 70. Its incidence and trends in Spain]. AB - INTRODUCTION AND OBJECTIVES: During the last years elderly population has been growing in all the occidental world. Consequently the number of elderly patients undergoing cardiac surgery has increased. The aim of this work is to know whether this increase has also taken place in Spain. METHODS: A survey among the different Units in the country was performed. The number and percentages of patients older than 70 years with coronary and valvular heart disease operated among 1991 and 1992 was analysed. Twenty-one of the 28 units replied (74%). RESULTS: The percentage of coronary patients older than 70 years operated in 1991 was 15.61% and 19.20% in 1992, a statistically significant increase of 21.84% (p < 0.001). However, there was no significant increase in the number of elderly patients undergoing valvular surgery. CONCLUSIONS: The influence of the elderly population on the activity in cardiac surgery is known to be significant; thus, a careful analysis of the health, social and economic implications seems to be mandatory. PMID- 7991922 TI - [The hemodynamic effects of the combination of milrinone in heart failure refractory to treatment with dopamine, dobutamine and/or nitroprusside]. AB - INTRODUCTION: Classical treatment of advanced heart failure is mainly based on the intravenous administration of inotropic drugs and vasodilators. Phosphodiesterase-III inhibitors, drugs whose effectiveness is not affected for the beta-receptor downgrading, may be particularly helpful in patients with severe heart failure refractory to conventional treatment with dopamine, dobutamine and/or nitroprusside. PATIENTS AND METHODS: We have analysed the hemodynamic effects of milrinone in 13 patients (11 men, 2 women, mean age 55 +/- 12 years) with advanced heart failure resistant to dopamine, dobutamine and/or nitroprusside. Basally, before milrinone was administered, mean cardiac index and pulmonary capillary wedge pressure were 1.9 +/- 0.4 l/min/m2 and 25 +/- 6 mmHg, respectively. Milrinone was administered intravenously with a initial dose of 50 micrograms/kg over 10 minutes and followed by and infusion of 0.75 micrograms/kg/min over 6 hours. RESULTS: During milrinone administration cardiac index and stroke volume index significantly increased (40% and 28%, respectively) (p < 0.05). Furthermore, systemic and pulmonary vascular resistance indexes significantly decreased (17% and 30%, respectively) (p < 0.05). Mean right atrial pressure and pulmonary capillary wedge pressure also decreased (36% and 20%, respectively), but differences did not reach statistical significance. Milrinone was well tolerated and no patient presented serious side-effects. CONCLUSION: Our results suggest that in patients with advanced heart failure refractory to conventional treatment with dopamine, dobutamine and/or nitroprusside, the addition of milrinone significantly improves parameters of systolic function. PMID- 7991923 TI - [Cardiovascular pharmacology (V). Pharmacological interactions in the patient on immunodepressant treatment]. PMID- 7991925 TI - [Pulmonary artery sling. A nuclear magnetic resonance study]. AB - We present a symptomatic newborn infant with anomalous pulmonary artery (pulmonary artery sling) studied by magnetic resonance imaging. Of the ones diagnosed by this method, is the first case published in our country and the eight of all that have been reported until this moment. The different methods used for the diagnostic, are discussed. We conclude that, the magnetic resonance imaging is at the moment, the elective diagnostic method. PMID- 7991924 TI - [Aortic pseudoaneurysm and acute myocardial infarct secondary to thoracic trauma]. AB - Three cases of traumatic cardiovascular disease following chest trauma in males with no previous ischemic heart episodes are presented. One of them coursed with a combination of myocardial infarction and aortic pseudoaneurysm in an unusual location. The others coursed with and acute myocardial infarction and an aortic pseudoaneurysm, respectively. It is also underlined the utility of transthoracic and transesophageal echocardiography as well as a routine hemodynamic evaluation in this kind of patients. PMID- 7991926 TI - [The pectoral implant of an automatic defibrillator by cardiologists in an electrophysiology laboratory]. AB - We have performed 2 implantations of transvenous automatic cardioverter defibrillator in a cardiac laboratory devoted to electrophysiology and pacemaker implantation. This is a preliminary experience with a novel implant strategy. Cardiologists were the primary operators. The automatic cardioverter defibrillator were placed in a subcutaneous pectoral region, with a non thoracotomy lead system. The automatic cardioverter defibrillator were two Medtronic 7219D PCD Jewel, with a Transvene system. There were no perioperative complications. Acceptable defibrillation threshold were obtained in both patients, 12 and 20 J, respectively. Leads were inserted percutaneously through the left subclavian vein. After 8 months of follow-up the patients continue to tolerate the device satisfactorily. Implantation of automatic cardioverter defibrillator systems by trained cardiologists in an electrophysiology laboratory is safe and feasible. Moreover, its cost-effectiveness is superior, the saving includes the surgeons, and the reduction of stay in unit of intensive care and hospitalization. PMID- 7991928 TI - [Complicated acute myocardial infarct]. PMID- 7991927 TI - [Primary pericardial angiosarcoma with multiple lung and a solitary liver metastases: the clinical and anatomicopathological findings]. AB - A case of 66-year-old woman with cardiac tamponade and bilateral pulmonary infiltrates is reported. These infiltrates were "pseudonodulars" and confluent. We practice pericardiocentesis and a hemorrhagic fluid is pulled out. Its cytology shown not neoplastic cells. She died and the necropsy shown an angiosarcoma of pericardium with multiple pulmonary and alone hepatic metastases. PMID- 7991929 TI - [Epidemiological data and the physiopathology of acute myocardial infarct]. PMID- 7991930 TI - [Prognostic stratification after myocardial infarct. Secondary prevention and rehabilitation]. PMID- 7991931 TI - [Coronary units in Spain: their planning, structure, staff and organization]. PMID- 7991932 TI - [Standards for managing the patient with an acute myocardial infarct]. PMID- 7991933 TI - [The treatment of uncomplicated acute myocardial infarct]. PMID- 7991934 TI - Effect of stimulus intensity on visually-evoked electrical brain activity maps in rabbit. AB - Stimulation by means of flashes is a commonly-used method in basic research into evoked potentials. Nevertheless, the different responses obtained at different luminous intensities, to which the inter-individual and intra-individual differences are added, determine the need to control this stimulus parameter for each experimental model. Maps of visually-evoked activity in the rabbit brain, obtained after monocular stimulation with flashes at different intensities of luminosity, are presented. Variation in the intensity of the luminous stimulus does not substantially affect the distribution of the electrical potential on the surface of rabbit brain described in previous articles. PMID- 7991935 TI - Modifications of tissular oxygenation and systemic hemodynamics after the correction of hypocapnia induced by mechanical ventilation. AB - The modifications of systemic hemodynamics, oxygen transport and tissular oxygenation in mechanically-ventilated critical ARF (acute respiratory failure) patients, after the correction of its hypocapnia by addition of dead space (VD) are determined. The prospective and randomized study was carried out in a multidisciplinary ICU. Fifteen ARF patients were studied within the first 48 hours of evolution. All the patients were intubated and mechanically ventilated. Three stages were delimited: I) 30 min after the beginning of anesthesia; II) 30 min after adding 30 cm of VD; III) 30 min after replacing the previous VD with a VD of 60 cm. Similar steady states had been reached when the measurements were taken. Ventilation parameters and FiO2 were kept stable. In stage I the patients presented a pure respiratory alkalosis and, with respect to hemodynamics, a hyperdynamic situation. In stage II the acid-base balance was normalized with a continuation of the hyperdynamic situation and an increase in mixed venous oxygen tension and saturation (PvO2 and SvO2) (p < 0.001). Stage III was characterized by a pure hypercapnic acidosis and an increase in capillary wedge pressure (CWP) (p < 0.05), right atrial pressure (RAP) (p < 0.001) and cardiac output (Qt) (p < 0.001); simultaneously, the systemic vascular resistances (SVR) decreased (p < 0.01), the PvO2, SvO2 and oxygen delivery (DO2) increased (p < 0.001); oxygen utilization coefficient (OUC) decreased (p < 0.01). The results suggest that the variations in PvO2 and SvO2 are a direct consequence of the modifications in blood flow.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7991936 TI - Metabolic clearance rate of insulin in type 2 diabetic patients treated with combined insulin and sulfonylurea therapy. AB - The metabolic clearance rate of insulin (MCRI) in 10 non-obese type 2 diabetic patients treated with either insulin alone or combined insulin plus sulfonylurea therapy is investigated. A classical 2-hour euglycaemic hyperinsulinaemic glucose clamp using the artificial pancreas was performed in a randomized order after two 6-week periods of treatment: either with subcutaneous injections of insulin alone or with insulin plus oral administration of the sulfonylurea compound glipizide at the dose of 3 x 10 mg/day. The MCRI was calculated knowing the constant insulin infusion rate (0.1 U.kg-1.h-1) and measuring basal and steady-state plasma free insulin and C-peptide levels. When the test was performed at the end of the period of treatment with insulin plus glipizide and 30 min after the ingestion of the last dose of 10 mg glipizide, plasma C-peptide levels were significantly increased and steady-state free insulin levels tended to be slightly higher whereas the metabolic clearance rate of glucose was not affected. The MCRI was significantly reduced by glipizide from 23.3 +/- 2.9 to 18.9 +/- 2.0 ml.kg-1.min-1 p < 0.05. These results demonstrate that the sulfonylurea glipizide decreases the MCRI. This effect may play a role in the hypoglycemic action of sulfonylureas. PMID- 7991937 TI - Hormonal control of exocrine pancreatic secretion in the isolated intact rat pancreas. AB - This study employs the isolated perfused rat pancreas to investigate the actions of the two gut hormones, cholecystokinin-octapeptide (CCK-8) and secretin on pancreatic juice flow and total protein output. Perfusion of the pancreas with either CCK-8 (100 pM) or secretin (100 pM) resulted in marked both pancreatic juice flow and total protein output. The effect of CCK-8 was three-fold larger compared to the responses obtained with secretin alone. Simultaneous application of CCK-8 and secretin (all 100 pM) failed to elicit either a potentiation or an additive effect in both pancreatic juice flow and total protein output. The net increases in both secretory parameters were reduced during combined application of CCK-8 and secretin compared to the responses obtained with CCK-8 alone. The results indicate that optimal concentrations of either CCK-8 or secretin can display marked secretagogue effects on the exocrine pancreas but when administered simultaneously they failed to elicit either an additive response or a potentiation in pancreatic juice secretion. PMID- 7991938 TI - Plasma glucose and lactate and hematological changes after handling stresses in the dogfish. AB - Hematological variables as well as blood glucose and lactate levels are determined in the Mediterranean dogfish after either cannulation surgery or handling by capture. The results show that both types of stress generate similar metabolic changes but somehow different hematological responses, since a cell loss is detected in cannulated fish, whereas an increase of cell volume is observed after handling. At the same time, surgery stress requires longer time to recover the basal levels than handling stress. PMID- 7991939 TI - Mechanisms of osteoporosis development during prolonged restriction of motor activity in dog. AB - The pattern in the mechanisms of osteoporosis development during prolonged motor activity restriction (hypokinesia) in animals has been studied. Twenty-four male dogs with initial body weights of 6.8 to 8.9 kg were divided into two equal groups: the 1st group were placed under ordinary vivarium conditions and served as control and the 2nd group were subjected to pure hypokinesia (HK) without any form of physical exercise and served as experimental animals. They were kept for 364 days in small individual wooden cages which restricted their movements without hindering food and water intake. Animals of each group were decapitated on the 120th, 240th and 360th day of the hypokinetic period and bones were x rayed, histological specimens were examined, mineralization or organic bone was measured, microroentgenographic analysis was performed and calculation was made of calcium, phosphorus, potassium and sodium. By the 120th and 240th day of the hypokinetic period bone resorption increased significantly, while by the 360th day it decreased significantly. The mature bone microstructures manifested a higher degree of mineralization, whereas the young bone microstructures exhibited a lower degree of mineralization. In bone, calcium content decreased, that of potassium increased, while sodium and phosphorus content remained unchanged. It was concluded that the development of osteoporosis in osseous tissues during prolonged restriction of motor activity of animals is associated not only to quantitative changes, which consist of a reduction of bone mass, but qualitative changes as well. PMID- 7991940 TI - Unconjugated bilirubin effect on 3H-ouabain binding to human fetal red cells. AB - Human fetal red cells show heterogeneity of 3H-ouabain binding sites. These cells were chosen as a model to look into unconjugated bilirubin effects on the primary active Na(+)-K+ transport mechanism. Evidences are presented suggesting that unconjugated bilirubin affects 3H-ouabain binding but not through a direct effect. This is supported by the fact that the "low affinity" subgroup sites of the last mentioned ligand persists after unconjugated bilirubin treatment of cells, whereas the "high-affinity" subgroup disappears. PMID- 7991942 TI - Mechanisms of autoimmunity and AIDS: prospects for therapeutic intervention. AB - The network theory of autoimmunity is presented with recent experimental data relevant to the understanding of the pathogenesis of AIDS. Schematically, effector T cells specific for self-antigens exist normally, but their activity is modulated and prevented by networks of regulatory T cells. As a result of mimicry between molecular components of microorganisms and self-antigens, autoimmune disease can be triggered by specific foreign pathogens which alter the state of activity of the network from suppression to activation. Conversely, by a procedure known as T-cell vaccination, autologous effector T cells re-injected after in vitro stimulation and attenuation may alter the state of the network from an activation to a suppression. Numerous observations are reviewed that support the concept of autoimmune activity in the destruction of non-infected T4 cells. Such activity is presumed to be triggered by an antigen of viral origin, the most likely, but not the only one, being the envelope protein gp 120. Based on this hypothesis, a T-cell vaccination procedure against effector T cells responsible for autoimmunopathic activity in HIV-seropositive patients is proposed, similar to the one known from experimental study of autoimmunity and presently being tested in human autoimmune diseases. Its purpose would be to prevent T-cell loss and the onset of immunodeficiency disease in HIV-seropositive patients. Apart from its potential therapeutic value, this procedure will have use as a therapeutic test from which insight will be gained about the immunopathogenesis of AIDS. PMID- 7991941 TI - Catalytic and regulatory sites in CF1. AB - The Ca(2+)-ATPase activity of the trypsin-activated CF1 presented a monophasic pattern, indicating that the active centres of the enzyme were acting with the same kinetic properties. The study of the effect of the anions cianate (OCN-) and thiocyanate (SCN-) on the ATPase activity showed the existence of cationic regulatory sites, capable of binding these modulators in a competitive way, resulting in the inhibition of the ATPase activity. Nucleotides ADP and ATP, at high concentrations, were competitive inhibitors for the substrate Ca(2+)-ATP. ATP, at low concentrations, presented an activating effect. The study of the combined effects of ATP (at low concentrations) and SCN- on ATPase activity revealed the existence of a non-competitive relationship between anions and nucleotides. The modification of CF1 with fluorescein isothiocyanate, a specific reagent that binds to amino groups of nucleotide binding centres, yielded a molar relationship FITC/CF1 = 4, both with the trypsin-treated and non treated enzyme. This specific incorporation took place on the alpha and, beta subunits of CF1, and resulted in a decrease of about 30% of the ATPase activity. These results are consistent with the existence of either three catalytic and three regulatory sites or four catalytic and two regulatory sites on CF1. PMID- 7991943 TI - The development of humoral immunological memory to a T-cell-dependent antigen requires thymic emigrant cells. AB - Immunological memory is embodied in the rapid and enhanced immune responsiveness to previously encountered antigens. Classically, memory would depend on the presence of small resting long-lived specific lymphocytes which, through clonal expansion after priming with antigen, would be present at higher frequencies than in naive animals. Here we report that T-cell-reconstituted athymic mice, which lack recent thymic emigrants, mount a primary response to a T-cell-dependent antigen, but do not develop memory or the capacity to produce specific anti-TNP IgG1 antibodies during the secondary immune response. On the other hand, if thymocytes are continuously provided during the secondary response, a typical secondary immune response is achieved with high levels of specific IgG1. These results lead us to propose that the development of humoral immunological memory cannot be explained solely by the long life span of primed T lymphocytes, but is rather a dynamic state dependent on the continuous presence of recent thymic emigrants and qualitative functional differences in responder T cells. PMID- 7991944 TI - Hyper-IgM syndrome. PMID- 7991946 TI - [Endocarditis: a clinical challenge]. PMID- 7991945 TI - Human CD40 ligand: molecular cloning, cellular distribution and regulation of IgE synthesis. PMID- 7991947 TI - [Pathogenesis of infectious endocarditis]. AB - The principles of pathogenesis of infective endocarditis are reviewed. Predisposing factors include not only rheumatic and congenital, but also degenerative cardiopathies, such as valvulopathy, and some extracardial factors of increasing importance. These abnormalities promote the development of nonbacterial thrombotic vegetations, which may become infected when bacteremia occurs. The ability of some microorganisms to produce an infective endocarditis is related to their capacity of adherence to valvular tissue. The pathogenesis of the infected vegetations explains most of the pathophysiologic mechanisms responsible for the variety of the clinical manifestations of infective endocarditis. PMID- 7991948 TI - [Clinical aspects and diagnosis of infectious endocarditis]. AB - The first step in the diagnosis of infective endocarditis is a high level of clinical suspicion. Only rarely are all the classic signs of infective endocarditis, namely fever, a new cardiac murmur, splenomegaly, anemia and embolic phenomena, found. Every organ system can be involved by embolic or immunologic complications. We have to look specially for manifestations in skin and mucosa, CNS, kidney, locomotor system and lungs. The clinical spectrum has changed over the last decades. More elderly patients, patients with prosthetic heart valves and i.v. drug users are affected. The traditional classification into acute and subacute infective endocarditis has been replaced by a classification based on the microbiological etiology or on the involved valve (native, prosthetic, left- or right sided). In particular, the clinical presentation of right-sided infective endocarditis differs from the left-sided one. A diagnosis of infective endocarditis has to be considered in every patient with unexplained fever or a multisystem disease. A definite diagnosis of infective endocarditis rests on a multidisciplinary approach that involves the clinician and the echocardiography and microbiology laboratories. PMID- 7991949 TI - [Transesophageal echocardiography in the diagnosis of endocarditis]. AB - Transesophageal echocardiography is a new diagnostic method for visualization of retrocardial structures and heart valves with high resolution. This retrospective analysis describes the use of and the findings by transesophageal echocardiography in patients suspected to suffer from endocarditis studied in three hospitals. 50 patients were studied; the diagnosis was confirmed in 64%, whereas 36% (controls) had other findings. The leading initial symptoms were fever and valvular incompetence. Laboratory parameters were altered in both groups with equal frequency. One or more diagnostic features were detected by transesophageal echocardiography in 88% of patients with endocarditis: vegetations (approximately with equal frequency on the mitral and the aortic, rarely on the tricuspid valve) were detected in 75% and/or abscesses in 22% of them. Only one patient in the control group with a history of endocarditis had vegetation-like structures on the aortic valve. Transesophageal echocardiography was on the average performed on the seventh day of hospitalization. With the exception of one female patient, all had been treated with antibiotics. Valve replacement was recommended in 65% of the patients with endocarditis and was in 59% also performed (single or double valve replacement), most frequently because of aortic or mitral regurgitation. The other patients were treated with antibiotics. Transesophageal echocardiography thus detects vegetations and abscesses in endocarditis frequently, findings that influence treatment in a significant manner. PMID- 7991950 TI - [Therapy of infectious endocarditis]. AB - The response of infective endocarditis to antimicrobial therapy is slow because host defence mechanisms in heart valves are absent, high bacterial densities occur in vegetations and the infecting agents have a low metabolic activity. In this situation, only an optimal antibiotic treatment can be effective; therefore early identification of the microorganism by means of blood cultures and the use of bactericidal antibiotics with proven efficacy in clinical trials are essential. The antibiotics should be administered intravenously, because constant and high serum levels are important. The choice of the empirical therapy is based on the patient's history, on clinical signs and symptoms as well as on some additional examinations in order to define the most probable organisms involved. As soon as the infecting agent is identified, the treatment should be optimized. A daily clinical examination of the patient and frequent laboratory controls are needed. In case of poor clinical response to the antimicrobial therapy, the search for complications is frequently more appropriate than changing the antibiotics. The duration of therapy depends on the infecting agent, the evolution and the antibiotic regimen that has been chosen. After treatment, blood cultures should be taken at four and eight weeks, since most relapses appear within this period. PMID- 7991951 TI - Sleep-disordered breathing in healthy aged persons: two- and three-year follow up. AB - We report the results of a study of the effects of sleep-disordered breathing in a cohort of healthy elderly subjects followed longitudinally for 3 years. In a comprehensive evaluation of daytime functioning, including medical history and physical examination, pulmonary function testing and neuropsychiatric testing, we found very little difference in the neuropsychiatric or medical sequelae between those subjects with moderate [apnea+hypopnea index (AHI) > or = 5] and low (AHI < 5) levels of sleep-disordered breathing at baseline. Although there were no differences in the electrocardiogram, pulse rate or cardiac history data, a mild association was found between indices of sleep-disordered breathing and pulmonary function. We conclude that moderate levels of sleep-disordered breathing in an otherwise asymptomatic healthy geriatric patient should probably not be considered pathologic in the short term. PMID- 7991952 TI - Chronic hypercapnia in obstructive sleep apnea-hypopnea syndrome. AB - In order to determine the relationship between chronic hypercapnia and anthropomorphic data, pulmonary function tests and slopes of ventilatory responses to hypercapnia (HVCR) and hypoxia (HVR), we studied 55 patients with sleep apnea-hypopna syndrome (SAHS). Patients were divided into hypercapnic, PaCO2 > or = 45 mm Hg (Group I, n = 23, PaO2 = 61 +/- 10 and PaCO2 = 50 +/- 5 mm Hg, and [HCO3-] = 30 +/- 4 mEq/l [means +/- SD]) and normocapnic (or eucapnic), PaCO2 < 45 mm Hg (Group II, n = 32, PaO2 = 76 +/- 10 and PaCO2 = 39 +/- 4 mm Hg and [HCO3-] = 25 +/- 3 mEq/l [means +/- SD]) groups. When compared to the normocapnic group, hypercapnic patients were significantly heavier (with greater body surface area) and had significantly more severe restrictive and obstructive defects and impaired HVR and HCVR. The means (+/- SD) of some of the data follow (* indicates p < 0.05 when Group I is compared to Group II): [table: see text] When subgroups of hypercapnic and eucapnic patients with similar lung functions were compared, the subgroups differed significantly in their weights; conversely, in subgroups with comparable weights, lung function tests differed significantly. These data suggest that the mechanisms of chronic hypercapnia are multifactorial, and we hypothesize that, in the face of repetitive apneas and hypopneas, increased weight and abnormal lung function tests interact and contribute to the generation and maintenance of hypercapnia. PMID- 7991953 TI - Cholinergic regulation of cataplexy in canine narcolepsy in the pontine reticular formation is mediated by M2 muscarinic receptors. AB - Both rapid eye movement sleep and cataplexy in the narcoleptic canine have been shown to increase after both systemic and local administration of cholinergic agonists in the pontine reticular formation. Furthermore, binding studies indicate an increase in the number of M2 muscarinic receptors in the pontine reticular formation of narcoleptic canines. In the present study we have investigated the receptor subtypes involved in mediating the cholinergic stimulation of cataplexy, as defined by brief periods of hypotonia induced by emotions, within the pontine reticular formation of narcoleptic canines. Specific cholinergic and monoaminergic agonists and antagonists, and excitatory or inhibitory amino-acid neurotransmitter receptor agonists, were perfused through microdialysis probes implanted bilaterally in the pontine reticular formation of narcoleptic canines, and cataplexy was monitored using the Food-Elicited Cataplexy Test and recordings of electroencephalogram, electrooculogram and electromyogram. In narcoleptic canines, bilateral perfusion with oxotremorine (M2 muscarinic) (10(-5)-10(-3) M) in the pontine reticular formation produced a dose dependent increase in cataplexy, which reached complete muscle atonia (status cataplecticus) during the highest concentration. In control canines bilateral perfusion with oxotremorine (10(-5)-10(-3) M) did not produce any cataplectic attacks, but did produce muscle atonia after the highest concentration. Bilateral perfusion with either McN-A-343 (M1 muscarinic) or nicotine (both 10(-5)-10(-3) M) did not have any effect on cataplexy in either narcoleptic or control canines. The increase in cataplexy in narcoleptic canines produced by local perfusion with carbachol (10(-4) M) followed by equimolar perfusion with a muscarinic antagonist was rapidly reversed by atropine (muscarinic) and gallamine (M2 muscarinic), partially reversed by 4-DAMP (M3/M1 muscarinic) and completely unaffected by pirenzepine (M1 muscarinic). Bilateral perfusion with excitatory, glutamatergic receptor agonists N-methyl-D-aspartate, AMPA (both at 10(-4)-10(-3) M) and kainic acid (10(-5)-10(-4) M) did not have any effect on cataplexy, whereas bilateral perfusion with the inhibitory GABAergic receptor agonist muscimol (10(-4)-10(-3) M) produced a moderate increase in cataplexy in the narcoleptic canines. Bilateral perfusion with numerous monoaminergic compounds, BHT-920 (alpha-2 agonist), yohimbine (alpha-2 antagonist), propranolol (beta antagonist) and prazosin (alpha-1 antagonist), did not have any effect on cataplexy. These findings demonstrate that cholinergic regulation of cataplexy in the narcoleptic canine at the level of the pontine reticular formation is mediated by M2, and possibly M3, muscarinic receptors. The effects of muscimol indicate that the stimulation of cataplexy might be elicited by local neuronal inhibition. PMID- 7991954 TI - Modafinil binds to the dopamine uptake carrier site with low affinity. PMID- 7991955 TI - Experimental sleep fragmentation. AB - Thirty-six healthy young men and women (age range 21-35 years) were studied in an experimental model of sleep fragmentation. On 2 nights sleep was disrupted by presenting tones to produce brief electroencephalogram (EEG) arousals (without shortening sleep time) and daytime function was assessed the following day with the Multiple Sleep Latency Test and a divided attention performance test. The fragmentation of sleep produced significant disruption of nocturnal sleep and reduced daytime alertness. Adaptation in EEG-defined arousals occurred from the 1st to the 2nd night of fragmentation. Threshold (measured indirectly) characteristics of EEG-defined arousals were somewhat different than those of previous studies requiring behavioral awakening. The percent of tone series producing arousal, number of tones necessary for arousal and duration of the arousal all reflected heightened thresholds in stage 3/4 and rapid eye movement (REM) sleep compared to stage 1 and stage 2 sleep. In the last 3 hours of sleep versus the first 3 hours, arousals occurred less frequently, required more tones to produce, resulted in shorter durations and in fewer sleep stage changes, except for REM sleep where the converse was the case. PMID- 7991956 TI - Asymmetry of instructed motor response to auditory stimuli during sleep. AB - Previous studies have demonstrated that motor activity during sleep is lateralized to the nondominant hand. There are two basic theories concerning this phenomenon: 1) The nondominant hemisphere is nonspecifically more alert or responsive than the dominant one, and 2) the lateralization to the nondominant side is task specific, reflecting the spatially oriented mode of information processing that is responsible for movements during sleep. We examined the motor responses to auditory stimuli during waking and sleep of 10 right-handed healthy subjects, who were instructed to switch off a tone stimulus by pressing a transducer that was attached to each hand. Sleep stage scoring was performed according to Rechtschaffen and Kales's criteria. During wakefulness and in all stages of sleep, with and without alpha activity occurring after stimulus onset, the dominant hand was used more, but during nonrapid eye movement S1 sleep the difference was not statistically significant. When alpha activity was present in the electroencephalogram after stimulus onset, the responses were significantly more lateralized to the right hand than when there was no alpha activity. During an actimetric home recording of both wrists of the subjects, there was an excess of left-sided movements during sleep as compared to waking. The results do not support the idea that the right hemisphere is generally more responsive than the left during sleep. They are, however, in accordance with the hypothesis that spatial information processing is a crucial factor in the nondominant lateralization of spontaneous sleep movements.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7991957 TI - Relationship between sleep spindles and hypersomnia. AB - Sleep spindles (SS) and K complexes constitute the physiological markers of stage 2 sleep. Because sleep allows a spontaneous thalamic manifestation in the form of SS, one could hypothesize that there is some kind of relationship between SS and the complaint of hypersomnia. To investigate this possible relationship we compared nonhypersomnolent subjects with hypersomnolent patients who carried a diagnosis of narcolepsy or idiopathic hypersomnia. SS were counted in well defined nocturnal stage 2 sleep segments, and the average SS density (number of SS in stage 2/minute stage 2) was tabulated for the entire night. Agreement between two independent scores was higher than 95%. The results show that the average SS density is higher in both cerebral hemispheres in the hypersomnolent group, especially in the idiopathic hypersomnia patients. At the beginning and at the end of the nocturnal sleep time, SS density is increased in this group compared with the normal one. These findings support the complaint of hypersomnia, mainly in idiopathic hypersomnia patients. This is in agreement with the notion that SS are generated by thalamic structures that serve a gatekeeping function during nonrapid eye movement sleep, and further suggests that their relative abundance expresses the power of that control. PMID- 7991958 TI - Insomnia in Vietnam era veteran twins: influence of genes and combat experience. AB - Genetic and environmental influences on insomnia were studied in 2,825 pairs of Vietnam era veteran male twins. The self-reported sleep problems studied included trouble falling asleep, trouble staying asleep, waking often, waking tired and a composite sleep scale. Twin correlations for each of the sleep problems were larger in monozygotic than in dizygotic pairs, with heritability estimates ranging from 0.21 to 0.42. There was no effect of common familial environment. Phenotypic correlations for combat experience and sleep problems were small, ranging from 0.00 to 0.09, with no differences seen in monozygotic and dizygotic twins. When the effects of genes and combat exposure were evaluated simultaneously, there was a significant genetic contribution to all sleep measures, but combat exposure was significantly associated only with overall sleep quality, waking often and having trouble staying asleep. PMID- 7991959 TI - Pure sleep panic: two case reports and a review of the literature. PMID- 7991960 TI - Associations of sleep with everyday mood, minor symptoms and social interaction experience. AB - Although there are strong popular beliefs about the value of a good night's sleep, there is very little documented evidence of day-to-day relations between sleep and well-being. In this study, covariations between sleep and both prior and subsequent daily states of well-being were studied in a healthy, employed sample. Thirty volunteers used pocket computers to complete a daily sleep diary and self-rating scales of mood, minor symptoms and social interaction experience. These were recorded every 2 hours for 14 days except during sleep periods. A pooled regression analysis showed small but significant relationships between many of the sleep and well-being measures. Sleep appeared to be more strongly related to subsequent well-being than prior well-being. An earlier onset of sleep was associated with better mood and social interaction experience the following day and was a better predictor than sleep duration. This result was interpreted to be consistent with the phase angle model of chronobiologic mood disorders. In general, the results suggest that the sleep disturbances found in affective disorders may not be pathological but instead represent the extremes of normal relationships between sleep and well-being. PMID- 7991961 TI - Bibliography of recent literature in sleep research. PMID- 7991962 TI - [Gastroesophageal reflux: new concepts on physiopathology and treatment]. AB - Multiple factors through a complex interaction are involved in the pathophysiology of gastroesophageal reflux disease. The transient or permanent failure of the antireflux barrier located at the esophagogastric union (lower esophageal sphincter and diaphragmatic crura) and the presence of gastric content to be refluxed determine the occurrence of reflux from the stomach into the esophagus, according to the physiologic gastroesophageal pressure gradient. The activity and mechanism of damage of the injurious components of gastroduodenal refluxate (hydrochloric acid, pepsin, bile acids and trypsin) are determined by the pH of the refluxate. The esophagitis is the final consequence of a prolonged contact time between the epithelium and several injurious components of gastroduodenal refluxate, and is due to the impairment of esophageal volume and acid clearance as well as to the failure of the epithelial resistance mechanisms. PMID- 7991963 TI - [Gastroesophageal reflux in pediatrics]. AB - The frequency of gastroesophageal reflux disease in pediatrics has increased. There is not a clear explanation, some believe there is more awareness of the disease, others believe that new formulas, which are richer in nutrients, may irritate the gastrointestinal tract of the infant. Clinically, children present with regurgitation-malnutrition, respiratory disease, and esophagitis. The medical treatment aims to improve the eating techniques, to decrease the gastric acid output, and to improve the motility function of the esophago gastrointestinal tract. Surgical treatment is rarely needed. PMID- 7991964 TI - Small bowel motility disorders. AB - Small bowel motility disorders may result in prolonged or accelerated transit and present clinically with such symptoms as nausea, vomiting, bloating, pain or altered bowel movements. These disorders result from derangements of neuromuscular control affecting extrinsic nerves, enteric plexuses or smooth muscle, or from structural disorders that may be congenital or acquired. Diagnosis depends on exclusion of mechanical obstruction or structural disease and assessment of motor function by measurement of transit and intestinal pressure profiles, and a search for the underlying disorder causing a neuropathy or myopathy. Management of stasis syndromes is based on restoration of good nutrition, treatment of bacterial overgrowth, prokinetic agents, antiemetics and surgery for localized disease. Patients with fast transit disorders require opioid agonists and, rarely, second-line treatments such as verapamil, clonidine or octreotide. PMID- 7991965 TI - Current concepts in the management of the irritable bowel syndrome. AB - In the irritable bowel syndrome gastrointestinal tract motility is disturbed from the esophagus to the colon, causing pain and altered function. When colonic motility is abnormal, the patient can experience either constipation or diarrhea in addition to abdominal pain and bloating. In constipated patients the postprandial colonic motility can increase normally after eating or the colon can remain motionless. Generally propagating contractions are absent in patients with constipation predominant irritable bowel syndrome. Propagating contractions are increased in frequency in patients with diarrhea, although the phasic contractions are decreased. Questionnaires discriminate between patients with structural disease such as ulcerative colitis and patients with functional disease, however they cannot differentiate between the different subgroups of patients with constipation predominant irritable bowel syndrome. Treatment strategies are beginning to focus on the underlying pathophysiologic abnormality. PMID- 7991966 TI - Evaluation and treatment of constipation. AB - Constipation is a symptom that usually reflects the existence of associated diseases. The clinical history, physical examination, and barium enema or colonoscopy should permit the diagnosis of extracolonic and structural colonic causes of constipation. A comprehensive evaluation of colonic transit and pelvic floor function in patients with functional constipation should categorize the underlying pathophysiologic mechanism, and optimize the selection of candidates for surgical operations and their results. PMID- 7991967 TI - Pathophysiology and management of fecal incontinence. AB - The successful management of fecal incontinence requires an understanding of anorectal function, careful delineation of the disorder by a detailed history and physical examination, and specialized studies of anorectal and pelvic floor function in selected patients. These studies include anorectal manometry, dynamic radiographic studies of the anorectum, pelvic floor neurophysiologic tests and anal endosonography. Therapeutic options include dietary modifications, behavioral programs, pharmacologic agents and surgery. Currently available diagnostic tests should result in optimal management of these patients. PMID- 7991968 TI - [Physiology of gallbladder motility and its clinical importance]. AB - The role of gallbladder motility (GBM) in gastrointestinal diseases has been frequently ignored. Recently however, the introduction of new diagnostic methods and data on the normal physiology of gallbladder emptying and refilling have placed this interesting area of gastrointestinal motility where it justly deserves. In this way it has been possible to recognize and further study the pathophysiologic mechanisms involved in some clinical situations with a higher than expected frequency of gallstones (GS). It has also been possible to identify with more clarity the role GBM has in the chain of events that lead to GS development and thus, to plan prevention or therapeutic strategies. The discovery of new drugs with effects on GBM have also permitted to further advance in the knowledge of normal physiologic mechanisms and to have access to possible future treatments. Also pathologic entities have been clearly defined, such as chronic acalculous cholecystitis. In this review we present recent knowledge on normal GBM physiology and its clinical applications as well consequences of its dysfunction. PMID- 7991969 TI - Sphincter of Oddi in health and disease. AB - Sphincter of Oddi (SO) is a dynamic structure located strategically at the confluence of the bile duct, the pancreatic duct and the duodenum. The advent of lateral viewing endoscope along with a minimally compliant pneumocapillary manometry system has greatly enhanced our ability to evaluate the SO in health and disease. These studies have shown that the SO motor function is a complex phenomenon controlled by a variety of neurohumoral agents. The sphincter also actively participates in the Migratory Motor Complex (MMC). The major function of the SO seems to be in regulating the flow of bile and pancreatic juice into the duodenum. By maintaining a basal tone, the sphincter diverts bile into the gallbladder under fasting conditions. On the other hand it functions as "a pump" as well to milk bile into the duodenum. Recent manometric studies also have unravelled a number of abnormalities involving the SO motor function often referred to as SO dysfunction. Most such patients respond favorably to sphincter ablation. Studies are underway to better define patients with SO dysfunction as well as to identify them using noninvasive investigations. PMID- 7991971 TI - [Biofeedback in the treatment of fecal incontinence]. AB - Four hundred and thirty seven consecutive patients with problems of motility were referred to, and examined at our third-level unit from 1987 to 1993. Forty seven (mean age 36.3 +/- 3.8, range 5-76 years; 25 females) fulfilled the established criteria for fecal incontinence. The mean period of total incontinence was 55.4 +/- 7.6 months (range 6 months to 21 years), with episodes of incontinence of 2.4 +/- 0.2 (range 1-7 a day). All patients were asked to complete a questionnaire in order to validate the incontinence diagnosis. A complete clinical history was obtained from each patient, and they were given laboratory tests, barium enema, recto-sigmoidoscopy, rectal sensitivity tests, recto-anal manometry, and biofeedback without electronic equipment. Twenty one normal subjects were used as a control group. Patients with fecal incontinence showed less rectal sensitivity (P < 0.01). The spontaneous recto-anal inhibitory reflex was not present in all forty seven. All the patients that completed their treatment were completely cured in a period of 4 +/- 0.5 months (range 16 days to 15 months), and follow-up continued for one to eight years. To sum up, this new therapeutic approach is beneficial independent of age, duration and cause of incontinence. The treatment is patient-friendly and economical. Doctors have changed their attitudes, and the quality of life of the patient has improved dramatically, thus providing clinical signification, and proof of the validity and applicability of this treatment: using biofeedback without electronic equipment in the treatment of fecal incontinence. PMID- 7991970 TI - Pharmacotherapy of gastrointestinal motor disorders. AB - Pharmacotherapy of gastrointestinal motor disorders is complicated by the large variety of drug targets and their interactions, the complex relation between contractile patterns and propulsion and the occurrence of regional and species differences. A number of drug classes are discussed: cholinergic agonists/antagonists, dopamine-antagonists, calcium-entry blockers and spasmolytics, serotonin-5-HT4-agonists, cholecystokinin-antagonists, motilin agonists, 5-HT3-antagonists, opiate agonists, and laxatives. The number of drug classes is increasing rapidly allowing a more specific treatment for the large number of gastrointestinal disorders related to disturbed motility. An interesting new development is the search for compounds interfering with transmitters of the non-adrenergic non-cholinergic nerves of the enteric nervous system a.o. nitric oxide (NO). PMID- 7991972 TI - Gastrointestinal motility: towards a new millennium. PMID- 7991973 TI - Oropharyngeal dysphagia: pathophysiology, clinical assessment and management. AB - The evaluation of dysphagia patient requires an understanding of the underlying physiology and the applicability of various evaluative techniques. This is best accomplished with a multidisciplinary team so each patient can benefit from a coordinated approach to the often complex problem of dysphagia. PMID- 7991975 TI - [Of apprenticeship and change]. PMID- 7991974 TI - [Motor disorders of the smooth muscle of the esophagus]. AB - Dysphagia and/or chest pain are the symptoms that characterize the motor abnormalities of the esophagus. These symptoms are not specific for motor disorders and can be seen with mucosal lesions. Symptom varies in severity and can be severe enough to put in risk the patient life. Motor dysfunction of the esophagus can be idiopathic, when it is not related to another systemic disease, or secondary, when it is associated to a generalized disease. Diagnosis and characterization of the motor disorders of the esophagus are best performed by manometry. In the present work, we expose some of the relevant clinical aspects and the manometric criteria currently accepted to classify motility disorders. Some treatment aspects are also reviewed. PMID- 7991976 TI - [Obesity. Recovering self-esteem]. PMID- 7991978 TI - [Florence Nightingale and nursing education]. PMID- 7991977 TI - [The hospital discharge of a high spinal injury patient. The experience of a regional hospital]. PMID- 7991980 TI - [Living menopause in health]. PMID- 7991979 TI - [Coronary patients. The effect of diet and the population characteristics]. PMID- 7991981 TI - [Care for the woman in the climacteric]. PMID- 7991982 TI - [Continent colostomy systems (I). The system of irrigation]. PMID- 7991983 TI - [Continuing education. 88. Medical-surgical. Burns]. PMID- 7991984 TI - [Marketing via the news]. PMID- 7991986 TI - Histologic type and gastric acid secretion in gastric cancer. AB - We investigated gastric acid secretion in 638 gastric cancer patients with respect to the association between aging and histologic types. In intestinal type tumors in which invasion is restricted to the mucosa, and in diffuse type tumors where the tumor invaded the serosa there was a significantly negative correlation between acid secretion and age. However, no relationship was found between gastric acid output and age in signet ring cell carcinoma. On the other hand, a significantly negative correlation between acid secretion and age was shown in male patients with well differentiated type and in females with signet ring cell carcinoma. In conclusion, low acid secretion related to aging may play an important role in developing cancer cells in intestinal type tumors especially in the male elderly, and in diffuse type tumors in the female elderly, respectively. PMID- 7991987 TI - Are tumours innervated? Immunohistological investigations using antibodies against the neuronal marker protein gene product 9.5 (PGP 9.5) in benign, malignant and experimental tumours. AB - The aim of the present study was to assess the innervation pattern in benign haemangiomata, malignant colo-rectal carcinomata and experimental malignant tumours transplanted into severe combined immunodeficient (SCID) mice using the general nerve fibre marker protein gene product (PGP) 9.5. An indirect immunohistological technique (using streptavidin-biotin complex formation) was used on paraffin wax sections of tumour tissues fixed in neutral buffered formalin. In 5/7 haemangiomata nerve fibres were detected in the vicinity of some tumorous blood vessels, though the majority of such vessels were without immunoreactive nerve fibres. In some cases the reaction product for PGP 9.5 appeared to be distributed in a diffuse perivascular manner. In the colo-rectal carcinomata, no intra-tumorous blood vessels received a nerve supply, though nerves were observed in the stroma supporting the tumour tissues. In the experimental tumours derived from either human colo-rectal carcinomata or breast carcinomata cell lines, no nerve fibres were detected within the tumours themselves. The conclusions reached were that tumour blood vessels are not innervated. Angiogenesis, which is a prerequisite for tumour growth, must, therefore, be regulated by a means other than neural. PMID- 7991988 TI - Growth inhibition in vitro of murine mammary adenocarcinoma cells by heparin and chemically modified heparins. AB - Heparin, a highly sulfated polysaccharide used as an antithrombotic and anticoagulant, inhibits proliferation of several cell types. We have investigated the effect of heparin and chemically modified heparins on the growth of a cell culture of a murine mammary adenocarcinoma (M3). We found that heparin inhibited the proliferation of M3 cells growing either with or without 2% fetal calf serum (FCS) in a dose-dependent and reversible fashion. Several heparins with different anticoagulant properties showed a similar antiproliferative effect. Histological assays showed that heparin was internalized and appeared in cytoplasmic vesicules. O-desulfated, O/N-desulfated N-acetylated and N-desulfated heparins lost their antiproliferative activity, while N-desulfated N-acetylated heparin significantly inhibited cell proliferation with or without FCS. The finding of an antiproliferative action of N-desulfated N-acetylated heparin which does not show anticoagulant activity suggests a possible therapeutic role for this compound as an antineoplastic drug. PMID- 7991985 TI - The diagnostic value of CA 27-29, CA 15-3, mucin-like carcinoma antigen, carcinoembryonic antigen and CA 19-9 in breast and gastrointestinal malignancies. AB - In the past decade, considerable interest has arisen for defining the role of various tumor markers in the diagnosis of cancer. This cross-sectional study evaluates four breast cancer markers (CA 27-29, CA 15-3, MCA and CEA) and two gastrointestinal (GI) markers (CA 19-9 and CEA) in 213 patients. Receiver operating curves (ROC) revealed a sensitivity for the 90% specificity cutoff for breast cancers compared to breast benign diseases of 70% for CA 27-29, 67.5% for CA 15-3, 52.5% for MCA and 40% for CEA. When GI tumors were compared to benign GI disease, the sensitivity for 90% specificity was 40.3% for CEA and 32.3% for CA 19-9. Comparison of breast cancer and GI malignancies with other malignancies leads to a marked shift of the ROC curve to the right and loss of specificity. Late stage for all breast and GI tumor markers was found to be a predictor of high serum antigen level (p < 0.001). The presence of liver metastases in breast cancer was associated with abnormal levels of CA 27-29 (p = 0.028). Pancreas adenocarcinomas had a higher CA 19-9 antigen level (p < 0.001) than other GI malignancies. CA 27-29 appears to be at least as sensitive and specific as CA 15 3 in patients with breast cancer. None of the above markers retain their specificity when compared with a control group consisting of other malignancies. PMID- 7991990 TI - Comparison of c-erbB-2 oncoprotein expression in tissue and serum of patients with stomach cancer. AB - Resected specimens of 288 primary stomach cancers (175 early cases and 113 advanced cases) and recurrent tumors or biopsy specimens of 21 recurrent or inoperable metastatic stomach cancers were examined immunohistochemically for expression of c-erbB-2 oncogene product. c-erbB-2 protein-positive staining was detected in 6.9, 15.9 and 28.6% of early, advanced and recurrent or inoperable metastatic stomach cancers, respectively, the difference being significant (p < 0.005). Four patients with advanced cancer showed positive staining in metastatic lymph nodes but not in the primary tumors. The results of tissue immunostaining were compared with c-erbB-2 protein levels in sera of the patients measured by an enzyme-linked immunosorbent assay. The levels of this oncogene product were consistently low in the sera of most of the patients with primary stomach cancers, regardless of whether or not c-erbB-2 protein was expressed in the tumor. However, in the recurrent or inoperable metastatic stomach cancers, 5 of 6 patients with c-erbB-2 protein-positive tumors showed elevated levels of c-erbB-2 protein in the serum. After following up c-erbB-2 protein levels in the sera of 3 patients during the period of chemotherapy against recurrent or inoperable metastatic disease, we found that the levels increased only in the late stage. These results suggest that, in stomach cancer, c-erbB-2 protein is likely to be excreted into the serum at a relatively late stage, reflecting systemic spread of the disease. PMID- 7991989 TI - Effect of host-organ environment on the in vivo and in vitro behavior of a murine mammary adenocarcinoma. AB - We investigated the role that organ environment may play in determining the homing of disseminated cells from a murine mammary adenocarcinoma moderately metastatic to lung (M3). Conditioned medium (CM) from normal lung was able to enhance both local and metastatic growth. It increased the number of lung colonies when inoculated together with tumor cells via intravenous or separately via intraperitoneal route. Several in vitro studies were performed in order to elucidate possible mechanisms. It was shown that lung CM stimulated the in vitro growth and the migration of M3 cells. Normal kidney and liver CM lacked all these capacities. PMID- 7991991 TI - pH-dependent LAK cell cytotoxicity. AB - In the microenvironment of many solid tumors the pH is considerably lower (mean pH between 6.6 to 7.2) than the pH in normal tissue (pH 7.0-7.5). Therefore, the influence of acidic pH on the cytotoxic activity of lymphokine-activated killer cells (LAK cells) after different culture periods was tested. K-562 human erythroleukemia cells were selected as target cells. Cell killing was measured using a two-color flow cytometric method. At physiological pH of 7.4, LAK cell mediated cytotoxicity ranged from 15 to 48% (E:T ratio = 50:1). The specific lysis of target cells was considerably reduced (up to 70% inhibition of specific lysis) under acidic conditions (pH 6.8, 6.3, 5.8). This effect was independent of donors, duration of the culture period, and the E:T ratio in the cytotoxic assay. As pH gradients surrounding tumor cells may reach values below pH 6.0 at the cell surface, the pH-dependence of LAK cell cytotoxicity could at least partially explain the inhibition of the natural immune response in solid tumors. Therapeutic immunological strategies concerning the enhancement of the natural immune response like LAK cell and IL-2 immunotherapy including IL-2 gene therapy may only be successful if a simultaneous inhibition of the acidification process and an elevation of tumor pH is achieved. PMID- 7991992 TI - Antioxidants in brain and the effect of hypoxia. AB - In the first part of our experiments we investigated the ascorbic acid content in five areas of the brain in 11 age groups of rats aged 1 to 90 postnatal days. In the area of the olfactory lobe the values vary within the range of 2.9-4.5 mmol/kg fresh weight, with a significant drop on the 21st, 35th and 90th day. In the cerebral cortex the scatter of values was similar with a significant drop on the 21st and 90th day. From the hippocampal area varying values were obtained, the drop on the 5th, 12th, 15th, 21st, 35th and 90th day being significant. The curve of the ascorbic acid content in the area of the vermis cerebelli has the typical shape of a wave. The initial drop is followed by a rise with the maximum on the 18th day. A significant drop was observed on the 5th, 7th and 90th day, a significant rise on the 12th, 15th, 18th and 21st day. In the area of the medulla oblongata the lowest ascorbic acid values in our experiment were recorded. A significant drop was observed on the 5th, 21 st, 35th and 90th day, a significant rise on the 18th day. All significances are referred to one-day old rats. In the second part of our experiments we studied the influence of acute and chronic hypoxia on the ascorbic acid content in liver, adrenal, plasma, cerebrospinal fluid and brain in 18-day-old rats. Due to acute hypoxia a significant decrease in ascorbic acid concentration in the adrenal occurred. Its levels in plasma and cerebrospinal fluid increased significantly compared with controls.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7991993 TI - [Serum fatty acids in premature neonates]. AB - In the past we have published several papers concerning the evolution of large spectrum of fatty acids in the brain or in the blood-serum in rats or in human newborns (and their mothers just after the delivery). Therefore we realized this study: the blood-serum spectrum of fatty acids in the healthy human newborns (n = 32) was compared with the spectrum of fatty acids detected in the blood-serum of human premature neonates (n = 22). The birth-weight in the control group was 3,882, in the premature neonates 2,137 g only. Fatty acids were measured as methylesters (FAME) using the method of gas chromatography and absolutely the same methodological approach as in our previous studies (33, 22, 23). The results were computed by biocybernet. dep. of Physiological institute and the statistics were evaluated by Mann-Whitney U test. It was established that the premature neonates show a distinct greater content (expressed in percentage) of saturated fatty acids and a smaller share of polyenoic FA (PUFA). A further marked difference consists in a significant lower of the n-3 FA and consequently a higher n-6/n-3 index. In premature neonates a significant increase of caprylic acid and arachidonic acid in the blood-serum was detected. The significance of described changes in the participation of single fatty acids in the premature neonates for their maturation, structural evolution especially of the brain cells and for therapy, is discussed. PMID- 7991994 TI - [The spectrum of fatty acids during lactation in women]. AB - The large spectrum of fatty acids (expressed in relative values) was studied in the breast-human milk during the first three weeks of the lactation (3rd, 5th, 10th and 20th day after delivery). All women passed the pregnancy and the delivery without any pathological syndrome and their neonates were found as a healthy and physiological too. No drug dependency was registered. Fatty acids were measured as methyl-esters (FAME) using the method of gas chromatography (1). During the 20 days after delivery and of lactation period, summarising the groups of fatty acid (saturated, monoenoic, PUFA n-3, n-6 and n-9) only few changes could be detected: the increase of the participation of saturated fatty acids of short-medium chain (8:0, 10:0 and 12:0) and of PUFA n-9. Compared with the most administered commercial formula Feminar, the visible differences in the participation of fatty acids were described. Finally: during the lactation we could obtain a large number of significant differences of such individual fatty acids as palmitic acid, arachidonic acid, eicosopentaenoic acid, linoleic acid ect. The possible reasons of such changes during the lactation are discussed and these results are compared with our previous data concerning the fatty acid- spectrum in blood plasma of healthy newborns and preterm or hypoxic infants. PMID- 7991995 TI - A comparison of haemocoagulation tests in the experimental endotoxin model DIC and in rats whole-body irradiated by 250 Gy. AB - Based on comparing results of tests followed in the present work between the endotoxin model of the disseminated intravascular coagulation (DIC) and irradiated groups of rats we consider that after the whole-body irradiation by a high dose of 250 Gy, the DIC occurs, in spite of the fact that the first stage- hypercoagulation condition, can be hardly observed. In the experimental endotoxin model, an increase of activated partial thromboplastin test (APTT) values and prolongation of the thrombin time was observed up to 24 hours in both endotoxin doses. After both endotoxin doses, the fibrinogen level was transiently decreased with its subsequent increase. The fibrin monomers correspond to decreasing the fibrinogen level. After the first dose, they were positive between the 3rd and 12th hours and after the second dose, the positivity was observed 6 hours after the application. The antithrombin III level was decreased after 12 hours in both endotoxin doses. The thrombocyte count was considerably reduced already from the 6th hour after administering endotoxin to the end of the experiment. Considerable changes of the thrombocyte aggregation were observed only 3 hours after administering the second dose. When comparing the resulting values of these tests with values observed in irradiated animals, then we can see a certain agreement in the nature of the changes after the exposure to 250 Gy. The fibrinogen level was transiently decreased 3 hours after irradiation, when considerable changes in the thrombocyte aggregation also occurred. PMID- 7991996 TI - Changes of certain biochemical values during whole-body exposures of rats to doses of 50, 100 and 250 Gy. AB - In the course of the postirradiation syndrome, changes of concentrations of certain components and of activities of certain enzymes occur in the blood serum. The data available in the literature concern doses lower than 10 Gy. In the present work, changes were studied of concentrations of mineral components, total proteins, glucose, creatinine and bilirubin and activities of liver transaminases, acid prostatic and alkaline phosphatases up to 24 hours after the whole body exposures of rats to doses of 50, 100 and 250 Gy of ionizing radiation. The changes observed--enhanced kalemia and activity of aspartate aminotransferase, particularly after the highest radiation dose used, and changes of the glycaemia (early increase with a subsequent considerable decrease)- support the assumptions based on the former results known from the literature. PMID- 7991997 TI - [Laboratory animals--suggestions, views, warnings]. AB - Basic informations are given on the Central Laboratory Animal Facility at the Hannover Medical School, Lower Saxony, which served as a model for similar facilities in nearly all medical schools in former West-Germany. Centralized facilities for laboratory animals as a service for bio-medical research are meanwhile common and well established in all universities of western countries. The lack of money is, certainly the paramount limiting factor hampering a soon realization of similar central facilities at czech and slovak medical schools. Another serious obstacle which could soon emerge comes from the psychologic ethical area. It is the emotional and unreasonable shift in the society's consciousness in western countries pertaining the use of animals for research which si promoted and perpetuated by plenty of legal and illegal actions of many potent organizations of so called animal rightists or activists or antivivisectionists. Such organizations do not yet exist in Czechoslovakia but the situation can change abruptly. The second part of this article consists in the description of the roots of such organizations and the description of their activities in the western countries in order to develop successful contra strategies. PMID- 7991998 TI - Hypoxia and the metabolic behavior of the immature brain. AB - The immature brain, affected by hypoxia (of certain degree and duration) shows several distinct differences as compared with the mature one. We demonstrated that previous hypoxia does not disturb the aerobic metabolism (in the newborns). The respiratory rate remains the same or its increase is accompanied by the improved coupling processes (the effect of DNP, increased incorporation of P32 into ATP fraction). Hypoxia elevates--at the same time--in the brain tissue of the youngest rats, the proportion of polyenoic n-3 fatty acids. This mechanism (hydrogen sink effect or hydrogen is drained to the synthetic work-elongation of fatty acids) could be decisive factor explaining the high resistance of the mammalian newborns against any lack of oxygen and at the same time their higher capacity for the recovery processes. This fact acquires a further physiological dimension. PMID- 7991999 TI - [The effect of ascorbic acid on adrenergic lipolysis]. AB - The effect of ascorbic acid on basal and adrenergic lipolysis was studied in rat epididymal adipose tissue in vitro. When adipose tissue was incubated with isoprenaline (ISO) for 1.5 h, the concentration-lipolytic effect curves of ISO were practically the same in the presence or absence of ascorbic acid used in concentration 100 and 1000 micrograms/ml. The lipolytic effect of ISO was not substantially altered even in the experiments in which adipose tissue was incubated with ISO for 4.5 h, but ascorbic acid (1000 micrograms/ml) was added only 1.5 h before the end of incubation. On the other hand, the contact of adipose tissue for 4.5 h with high concentration of ascorbic acid (1000 micrograms/ml) induced significant decrease of maximum adipokinetic effect of ISO. Contrary to catecholamine stimulated lipolysis, the basal rate of lipolysis was enhanced by ascorbic acid. Inhibition of maximum lipolytic effect of catecholamines (isoprenaline and noradrenaline-NOR) and oxedrine (isopropylnoroxedrine) was also seen when adrenomimetics were added to incubation medium 1.5 h before the end of 4.5 h incubation of adipose tissue with ascorbic acid. Decreased reactivity of adipose tissue to catecholamines persisted when the tissue, after 3 h incubation with ascorbic, was transferred into fresh medium with ISO and ascorbic acid. Preincubation of ascorbic acid (3h) in the incubation medium without adipose tissue, followed by subsequent addition of the tissue and catecholamines (NOR, ISO) and 1.5 h lasting incubation, did not influence the adipokinetic effect of NOR and ISO. These facts indicate that ascorbic acid decreases the lipolytic effect of catecholamines as a result of its effect on adipose tissue but not on the incubation medium.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7992000 TI - [3H-dihydroalprenolol binding to beta-adrenergic receptors in adipocyte membrane fractions of rats premedicated with estrogens]. AB - Oestradiol administration in vivo has been shown to potentiate the adrenergic lipolysis in vitro in rat epididymal adipose tissue; one of the possible explanations of this oestradiol effect might be the direct influencing of beta adrenergic receptors. In order to show this possible mechanism of action, in direct radioligand binding studies we have estimated the specific binding parameters of beta-adrenergic receptors in controls and in vivo pretreated rats by a single dose of oestrogen (200 microgram.kg-1 s.c. 24 hours prior sacrification of rats). Beta-adrenergic receptor binding studies we performed with membrane fraction of homogenates of epididymal adipose cells, the radioligand used was L-[3H]-dihydroalprenolol (3H-DHA). No clear-cut differences in the saturation curves of 3H-DHA were found between control and pretreated oestradiol rats; the density of beta-adrenoreceptors (Bmax) was practically identical (269 v. 270 fmol.mg-1 protein) and also differences in dissociation constants (Kd) of both groups were minimal (1.05 vs. 0.95 nmol.1-1). Minimal differences between control and oestradiol pretreated rats were also found in displacement studies, where the effects of 1-isomers of norepinephrine and epinephrine was tested. Thus, it seems possible that the potentiating effect of in vivo pretreatment by oestradiol on adrenergic lipolysis of epididymal adipose tissue in vitro is not caused by the direct influencing of beta-adrenergic receptors. The explanation of this effect will be necessary to search on other steps of the adrenergic reaction which lead to lipolysis or in influencing other receptors (e.g. alpha-adrenergic receptors). PMID- 7992001 TI - Does chronic nitrate therapy induce tolerance to short-acting ones? AB - The aim of this study was to ascertain whether long-term nitrate administration (therapy by 120 mg ISDN or 16 mg molsidomine) decreases the efficiency of administered short-acting nitrate by the mechanism of tolerance. Fourteen male patients (mean age 56 years) with stabilized angina (IIIrd degree) were included and stress test with standard workload of 75 W was performed at the beginning of the study after cessation of therapy. Subsequently, the test was repeated after administration of 2.5 mg ISDN (IsoMack spray). The period of time until maximal load increased more than twice (4.0 +/- 1.3 vs 9.1 +2- 3.3 min. mean +/- SD). Afterward, patients were treated by ISDN 120 mg (IsoMack 120) once a day or molsidomine 8 mg (Corvaton ret.) twice a day; both drugs were interchanged after the period of 6 weeks. Stress tests were repeated at the end of these therapy periods (before and after application of short-acting nitrate). During 120 mg ISDN therapy, the time until maximal load after the application of 2.5 mg ISDN increased analogously (6.2 +/- 1.8 vs 9.6 +/- 3.7 min) and similarly after molsidomin therapy (5.5 +/- 1.7 vs 10.0 +/- 4.1 min). These results indicate that stress tolerance increases after short-acting nitrate administration significantly also in patients treated by high doses of long-acting nitrates (ISDN or molsidomine). Inducing of tolerance to short-acting nitrates was not observed. PMID- 7992002 TI - Glycosaminoglycans in urine of type 1 diabetic patients. AB - Diabetic nephropathy is accompanied by changes of glomerular and tubular functions manifesting already in the early stages by an increase of glycosaminoglycans excretion into urine. We evaluated urinary glycosaminoglycan excretion in 38 Type 1 diabetic patients with no markers of developed nephropathy. Glycosaminoglycan excretion related to creatinine concentration was significantly higher in diabetic patients with or without retinopathy than in healthy persons (3.9, 1.2-12.7 or 3.7, 0.9-15.9 vs 2.0, 0.8-5.1 micrograms/mumol creatinine, p < 0.01). A positive correlation between glycosaminoglycan excretion and albuminuria was observed in all diabetic patients (r = 0.60, p < 0.01). Urinary glycosaminoglycan excretion did not correlate with serum fructosamine concentration. PMID- 7992003 TI - Neurohumoral relations in neurological and psychiatric patients. AB - Sixteen patients-epileptics, alcoholics, psychotics and post-contusion cases-were subjected to neurological, psychiatric, psychological, morphological (X-ray, CT, NMR), physiological (EEG, polysomnography, evoked potentials), immunological and SPECT examination. Most had CT and SPECT signs of focal brain damage. The results were but exceptionally due to injury, most were of unknown etiology. This tallied with EEG focal abnormalities, mainly sleep disorders, sometimes subjective ones, but invariably detectable objectively. In each case there was REM, in some also NONREM sleep deficiency. Half of the cases were tested immunologically, each time with positive results: increased levels of acute-phase protein and stress reaction proteins. As copious literature and our experience show, the above pathological condition, rather than being accidental, constitute regardless of etiology, an integrated entity which could be called "programme cerebropathy". The primary role is played there by the epileptic focus and its properties, in particular, the speed of discharge and localization and brain stem humoroergic systems, i.e., their performance and mutual balance. There is a program sequence of events, first, and epileptic focus acting on the neighborhood, the rise of secondary and tertiary foci, and influence over the thalamocortical system. Soon afterwards, epileptic activity begins to act on brain-stem structures. This results in changes in sleep, mood, psychic output, immunity, endosecretion, and in paroxysms. PMID- 7992004 TI - Melanosome--a sophisticated organelle. AB - Melanosome is a clear out organelle of its own. The experience of the authors in the melanosome investigation has been reviewed and put to context with the literature data. Melanin moiety, a prominent feature of melanosome, was found to vary between 20-60 weight %. Melanosome concentration in pigment tissues was demonstrated to be remarkably high which explains their capacity to perform various functions both cytoprotective and cytotoxic-ascribed to the presence of melanin. Putative relation of melanosomes to other cell organelles was critically analysed. Systems of melanosome maturation were explained. The ultrastructure of melanosomes determined by the quality of their protein matrix was described and basic morphometric data summarized. The importance of the compartmentalization of melanogenesis was underlined and the fragility of melanosomal limiting membrane shown. The melanosome degradation repeatedly observed by electron microscopy has not been confirmed by biochemical means. PMID- 7992005 TI - Ultrastructure of the tubal chorion. AB - The chorion of five cases of ampullar pregnancies aged 9-11 weeks was examined in electron microscope. The appearance of chorion is affected by massive haemorrhage into the tubal lumen which occurs in this type of tubal pregnancy and causes its segregation from the tubal wall. The chorionic villi scattered in haematoma show different structure. The electron microscope investigation reveals that many chorionic villi possess the intact microvillous surface and are similar to normal villi of the intrauterine chorion. The development of syncytiotrophoblastic organelles especially as far rough endoplasmic reticulum, Golgi apparatus and mitochondria suggests that the syncytiotrophoblast may for some period be functional under these unfavourable conditions. The chorionic villi imprisoned in blood clot are often covered by fibrin deposits, their syncytium shows considerable folded nuclei with coarse chromatin aggregations, extremely dilated and degranulated endoplasmic reticulum. When syncytium degenerates the fibrinoid sheets invest the isolated portions of the villi. The necrotic villi as well as the cells of cytotrophoblastic islands are embedded in the fibrinoid masses. The cytotrophoblastic cells resembling the cells of basal plate in placenta are found in the tubal wall adjacent to the haematoma. PMID- 7992006 TI - Filipin test for diagnosis of Niemann-Pick disease type C. AB - The test is based on the reaction of unesterified cholesterol with fluorescent antibiotic filipin giving a strongly fluorescent, stable cholesterol-filipin complex suitable for in situ detection. The test is useful for the evaluation of impaired cholesterol esterification in cultured cells (fibroblasts or others) in Niemann-Pick disease type C. PMID- 7992007 TI - Infantile sialic acid storage disease (ISSD). Report on first case in Czech Republic with biopsy and autopsy findings. AB - The first case of infantile sialic acid storage disease in Czech Republic is presented in a four-and-half year-old girl. The clinical phenotype consisted of moderate hepatosplenomegaly and skin hypopigmentation, early psychomotoric and developmental arrest, associated with truncal ataxia and lower extremities spasticity, extinguished acoustic and visual perception (optic atrophy without macular alteration) and remarkable automutilation phenomena. The appearance was normosomatic and there were minimal dysostotic changes. Skin and liver biopsy displayed moderate amount of lucent storage lysosomes in epithelial, mesenchymal, and neural elements. Alder-Reily granules were found in the bone marrow and peripheral blood cells. The urinary excretion of mucopolysaccharides and oligosaccharides was not increased. The autopsy showed heterogenous neuronal and glial brain storage (lucent lysosomes, lipopigment, membranous cytoplasmic bodies), severe hypomyelination and severe storage in the splenic sinus endothelium. Diagnosis was made by proving thirteen fold increase of free sialic acid in the fibroblast culture. It is pointed out that in the case of a mucopolysaccharidosis-like storage disease unexplainable by a hydrolytic enzyme deficiency, it is the enzyme product storage which must be suspected. At present, the only candidate is the sialic acid storage disease. PMID- 7992008 TI - Plasma concentrations of some cardiovascular humoral factors in essential hypertension and their changes during the treatment with converting enzyme inhibitor lisinopril. AB - Plasma concentration of two main cardiovascular substances - atrial natriuretic factor (ANF) and endothelin - were studied in control subjects (n = 21) under basal conditions and 90 minutes after oral administration of glucose. In hypertensive patients (n = 21) these determinations were repeated after 12 weeks treatment with an angiotensin I-converting enzyme inhibitor lisinopril (Prinivil, Merck Sharp and Dohme). While basal and post-glucose ANF concentrations did not differ in controls and hypertensive patients, a tendency to the higher endothelin levels was found in our group of essential hypertension when compared to normotensive subjects. Glucose loading did not change significantly ANF concentrations in any studied group but significantly lowered plasma endothelin in both controls (from 13 +/- 0.95 to 9.50 +/- 0.95 fmol/ml) and hypertensive patients (from 15.05 +/- 1.23 to 12.15 +/- 1.03 fmol/min). Treatment of hypertensive patients with lisinopril paradoxically increased concentrations of ANF (from 6.43 +/- 2.53 to 11.47 +/- 4.90 fmol/ml) and lowered that of endothelin (from 15.05 +/- 1.23 to 12.17 +/- 1.58 fmol/ml). From our findings we may suggest that the relative predominance of the vasoconstrictor (endothelin) over the vasodilator (ANF) humoral substances might participate in pathogenesis of EH and that the reversal of this disadvantageous ratio after lisinopril (increase of ANF and decrease of endothelin) might contribute to the blood pressure reducing effect of ACEI. The drop in plasma endothelin after glucose remains so far unexplained consequence of glucose loading in both control and hypertensive subjects. PMID- 7992009 TI - Pepsinogen polymorphism in human gastric mucosa in relation to gastric diseases. AB - The human stomach mucosa contains two main group of gastric proteinases. Both pepsinogen A (PGA) and pepsinogen C (PGC) consist of molecular variants, isozymogens, which can be separated electrophoretically, PGA was found to consist of five isozymogens (Pg1-Pg2), and PGC of two isozymogens (Pg6 and Pg7). Five hundred zymograms were examined and electrophoretic mobility of pepsinogens from patients with gastric cancer was found to be higher than from other gastric diseases. The ratio of isozymogens Pg3 to Pg5 differs in to great extent in various disease. Patients with ulcer disease have this value higher than 1, but patients with gastric cancer lower than 1. Patients with gastric ulcer have lower occurrence of Pg1 and SMP in antrum. In patients with gastric carcinoma lower concentration of PGA and also ratio PGA to PGC are observed. PMID- 7992010 TI - [Are we typing HLA-A, B, and C antigens correctly?]. AB - Analysis of the results of check-up examinations of HLA-A,B,C antigens in 62 cases of paternity demonstrated complete agreement of the first and second expert in 58.06% cases. Differences in 26 cases (= 41.94%) consisted in 10 cases in the detection of different HLA antigens from the first and second expert (owing in 6 cases to the different conclusion of the experts' account) and in 16 cases in the evidence of some HLA antigen only from one expert (usually by the revision). The most frequent errors pertained to the evidence of HLA antigens A28, A29, A30/31, A33, B16, B17, B21, B18, Bw22 and of the antigens of HLA-C locus; however, the well demonstrable HLA antigens A9, A10, B8, B13 were also not proved. The causes of the mistakes were analysed. It is necessary to avoid the errors of the administrative character and by the evaluation of the results in doubtful cases. PMID- 7992011 TI - [Pregnancy after chemotherapy in malignant forms of gestational trophoblastic disease]. AB - The authors reviewed the subsequent pregnancy experience in patients with malignant gestational trophoblastic disease who were managed at the Czechoslovak Trophoblastic Disease Center between January 1981 to December 1990. Thirty-five women who conceived following successful chemotherapy of gestational trophoblastic disease subsequently became pregnant a total of 53 times. Twenty seven of these 53 pregnancies or 51% terminated in live-born infants. Major or minor congenital malformations were not detected. Those subsequent pregnancies concluded in 23 full-term deliveries (85%) and 4 premature births (15%). Primary cesarean section was performed for 5 (19%) women. Three or 6% ended in spontaneous abortion, one or 2% ended in mola hydatidosa partialis and mola hydatidosa completa. Sixteen pregnancies or 30% terminated in therapeutic abortion. Five women or 9% are now pregnant. Those patients who are treated successfully with chemotherapy should be reassured that they can anticipate a normal reproductive outcome in later conceptions. PMID- 7992012 TI - [A remembrance of Professor Frantisek Mares (1857-1942)]. PMID- 7992013 TI - The changes in the myocardium under experimental conditions. AB - An effect of different interventions on the electron microscopic structure and morphometric parameters of the myocardium were studied. Application of cyclophosphamide and isoprenaline in the experimental animals allows the similar changes of mitochondrial partial volume like hypoxic periods of cardiac surgery by coronary bypass operation. Although the initial agents are different, the primary affected structures are sarcoplasm and mitochondria, whose proportions change promptly. The primary effect may be connected with alteration of membrane permeability caused by increased osmotic active ion transport on responsibility of the inhibited Na, K-ATP-ases (or F0 F1-ATP-ases irreversibly altered in mitochondria). The morphometric evaluation confirms not only statistically significant differences among the experimental groups treated by cyclophosphamide, isoprenaline and by cardioplegic ischaemic periods in the human myocardium but also by application of physiological saline in the control groups. Comparing the morphometric evaluation by manual processing with computer mediated image analysis we can conclude that the results correspond upon conditions of the specific defined raster for Weibel's intersection test only. PMID- 7992014 TI - [Ethanol metabolism and pathobiochemistry of organ damage--1992. I. Metabolism of ethanol by alcohol dehydrogenase, cytochrome P450IIE1 and catalase]. AB - Three metabolic pathways of ethanol in human body have been described thus far: 1) alcohol dehydrogenase (ADH), 2) microsomal oxidizing ethanol system (MEOS), 3), catalase. The main role in alcohol metabolism is being payed by cytosolic enzyme, alcohol dehydrogenase, which catalyses metabolism of ethanol to acetaldehyde. It occurs in many dimeric isoenzyme forms which are divided into three classes, according to substrate specifics and other chemical-physical properties. ADH is regulated by development and sex, its activity has been described in many tissues (liver, stomach, kidneys, ovaria, uterus, testes, retina, iris). In 1991 Yoshida found a new gene of alcohol dehydrogenase-ADH 6. 4 hydroxyalkenals, cytotoxic products of lipid peroxidation, are also substrates of ADH. Acetaldehyde is further metabolised by aldehyde dehydrogenase (AIDH) to acetate. AIDH occurs in the form of several isoenzymes in cytosole, mitochondria and microsomes of almost all tissues. Acetaldehyde thus binds to nucleic acids, phospholipids and especially to proteins, it may change their structure and function. In activates collagen synthesis and stimulates lipid peroxidation. Human body may be impaired by immune reaction caused by acetaldehyde binding proteins. Acetaldehyde has the function of a hapten. In 1968 Lieber and DeCarli described microsomal ethanol oxidizing system (MEOS). MEOS is one of cytochrome P450 isoenzymes, now called P450IIE1. Having a gene on chromosome 10, composed of 492 amino acids, this isoenzyme is present in cytoplasmatic reticulum. It is inducible and in case of chronic alcoholism, it accelerates elimination of ethanol from the human body. Inducted P450IIE1 is also present in Kupffer cells which participate in fibrogenesis of liver tissue and produce interleukin 1.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7992015 TI - [Ethanol metabolism and pathobiochemistry of organ damage--1992. II. Relation between ethanol metabolism and free radicals, and the metabolism of saccharides and amino acids. Ethanol as a carcinogen. Drug interactions with ethanol]. AB - Ethanol metabolism induces formation of free radicals which are responsible for lipid peroxidation of biological membranes with subsequent aldehyde formation (malondialdehyde,4-hydroxy-nonenal). These aldehydes are competitive or mixed inhibitors of aldehyde dehydrogenase, and they cause an increase in hepatocellular toxicity of aldehydes. The activity of antioxidative systems in human body after chronic as well as acute ethanol intake is being reduced. Interference of ethanol metabolism and gluconeogenesis is caused by inhibition of intake substrates or by decrease NADH/NAD+, ratio in hepatocyte. The blood level of glucose decreases, lactate level increases as well as the ration of lactate, pyruvate and NADH/NAD+ which inhibit cytosole pyruvate carboxykinase. An acute ethanol administration reduces the concentration of most amino acids in plasma by ethanol oxidation impacts on increase of NADH/NAD+ ratio or by mechanism mediated by beta-adrenergic receptors. Chronic alcoholics develop tolerance to decreased plasmatic levels of amino acids. Accumulation of proteins in liver may be explained by larger amount of proteins binding to fatty acids, and also by diminished degradation of proteins with decreasing autophagosome and autolysosome formations. Alcohol is one of carcinogenic factors. Ethanol, acetaldehyde and originating free radicals impaired the DNA repairing enzyme. Binding itself to DNA, acetaldehyde changes DNA properties. Ethanol may also function as a co carcinogen due to its ability to increase disolution and absorption of carcinogens. Chronic alcoholism induces cytochrome P450 which takes part in the activation and metabolism of carcinogens. Mutual interaction of drugs metabolism and ethanol is connected mainly with cytochrome P450-MEOS. Acute ethanol intake inhibits MEOS, as MEOS gives preference to ethanol as a substrate, however, chronic alcoholism induces MEOS.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7992016 TI - [Ethanol metabolism and pathobiochemistry of organ damage--1992. III. Mechanisms of damage to the gastrointestinal tract and the liver by ethanol]. AB - Alternations of stomach mucose caused by ethanol are in direct correlation with its concentration. ADH in stomach mucose is an efficient barrier against ethanol system toxicity. It stimulates higher secretion of HC1, dilutes protective barrier of mucose and phospholipids in membranes. Inflammatory reaction also participates in the damage of stomach mucose, with a share of products of arachidonic metabolism and free radicals. After ethanol administration the pancreas blood circulation diminishes and resistance in microcirculation increases. This can cause necroses in periphery of lobules. Activated phospholipase C may result in hypersecretion of Ca2+ dependent proteinkinases. Ischemic changes participate in alcohol impairment of pancreas and increase its vulnerability to enzyme attract and free radical reactions. Ethanol excesses may result in diarrhoea, dyspepsia, malnutrition and cause morphologic alternations of intestinal mucose (erosion, hemorrhagia). Absorption of nutrients and vitamins is affected by inhibition of active transport or by decrease of enzyme activity. Ethanol increases mucose permeability, alteres intestinal motility and damages absorption of water and electrolytes. In chronic alcoholics lower villi and changes in bacterial flora are described. The following mechanism of ethanol caused liver injury are observed: acetaldehyde toxicity, change in NAD+/NADH ratio connected with acidosis, cytoskeletal impairment, inhibition of protein synthesis and their secretion, relative perivenular hypoxia, activation of fibrogenesis, increased formation of free radicals with lipid peroxidation and immunological reaction. In hepatocyte there are morphological changes (megamitochondria, etc.) and functional changes (inhibition of glycolysis, inhibition of Krebs cycle and beta oxidation of fatty acids). Ethanol intake activates leukocytes, trombocytes, endothelial and Kupffer cells and their mediators, which result in increase of collagen and proteoglycans synthesis furthermore in fibrotic changes in liver. PMID- 7992017 TI - [Ethanol metabolism and pathobiochemistry of organ damage--1992. IV. Ethanol in relation to the cardiovascular system. Hematologic, immunologic, endocrine disorders and muscle and bone damage caused by ethanol. Fetal alcohol syndrome]. AB - Peripheral vasodilatation with increased cardiac output, tachycardia and increased blood pressure are described after alcohol administration. An increased HDL-cholesterol is found in moderate drinkers (both HDL-2 and HDL-3 fractions), with diminishing risk of coronary heart diseases. Acute ethanol intake causes an increased the level of triglycerides without changes in HDL-cholesterol level. This may be put into correlation with higher incidence of cardiovascular diseases in so-called "week-end" drinkers. Alcohol abuse may result in central diabetes insipidus. An increased elimination of lactate diminishes tubular secretion of uric acid with subsequent secondary hyperuricemia. Ethanol reduced the number of lymphocytes, reduces phagocytosis by macrophages and diminishes the activity of NK-cells. Bone marrow cellulity diminishes with the subsequent reduction in erythropoiesis, trombopoiesis and leukopoiesis. Alcohol may cause sideropenic and megaloblastic anemia. There are two forms of alcohol muscle injury: the acute one, with myonecrosis and inflammatory reaction, and chronic one, with muscle weakness and atrophy. Alcohol is one of etiologic factors of osteoporosis. An acute intoxication result in transitory hypoparatthyreoidism, while chronic ethanol intake make grow the PTH level and decreases the level of D vitamin metabolises. Stimulation of cortisol secretion, decrease of testosterone level and a reversible decrease of T3 and T4 levels have been described following ethanol administration. Hypothalamic-pituitary-adrenal axis suffers alteration in alcoholics, and secondary amenorrhea is observed in female alcoholics. Ethanol behaves as an agonist on GABA receptor. Fetal alcohol syndrome together with Down's syndrome and spina bifida are the most frequent reasons of mental retardation in developed countries. Toxicity of ethanol affects the whole pregnancy period.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7992019 TI - [Polysomnography findings in middle-aged and elderly narcoleptics]. AB - The comparison of 24 hours polysomnographic recordings of middle-aged narcoleptic subjects (39-51 years, group A) with 11 twenty four hours and 3 nighttime recordings of elderly narcoleptic subjects (aged 60-72 years, group B) using T test for non paired values was made. No difference was found in parameters of nighttime registrations: total sleep time (A:510.4 +/- 71.2 min., B: 475.9 +/- 92.4 min), intrasleep wakefulness (A: 107.5 +/- 75.3 min., B: 112.3 +/- 65.3 min), latencies of sleep stages (1NREM-A: 3.4 +/- 2.8 min, B: 4.3 +/- 3.7 min, 2NREM-A: 7.4 +/- 7.6 min, B: 6.6 +/- 12.7 min, 3NREM-A: 27.2 +/- 10.4 min, B: 51.6 +/- 62.6 min, REM-A: 62.2 +/- 59.5 min, B: 64.6 +/- 71.6 min), relative duration of each sleep stage (1NREM-A: 20.0 +/- 9.5%, B: 21.4 +/- 13.2%, 2NREM-A: 51.3 +/- 8.5%, B: 51.9 +/- 14.2%, 3 +/- 4NREM-A: 8.2 +/- 6.5%, B: 7.2 +/- 6.5%, REM-A: 20.4 +/- 4.5%, B: 19.1 +/- 5.7%), and sleep continuity index (A: 0.83 +/- 0.11, B: 0.81 +/- 0.11). Total sleep time in the daytime was similar (A: 160.5 +/ 53.8 min, B: 180.5 +/- 59.9 min), the number of sleep episodes during the day was in elderly patients higher (A: 3.4 +/- 1.2, B: 4.8 +/- 1.3, P < 0.05) and the number of sleep onset REM periods was in elderly subjects slightly higher (A: 1.9 +/- 1.1, B: 2.7 +/- 1.7). The authors conclude that the nocturnal sleep of both age groups of narcoleptic subjects is disturbed and the character and the intensity of this disturbance are similar. Elderly narcoleptic subjects displayed more daytime sleep periods. PMID- 7992018 TI - Prevalence of HBeAg and HBsAg seroconversion in patients with chronic hepatitis B. AB - In 37 patients with chronic hepatitis B in the stage of active viral replication the authors tried to assess the time of seroconversion of HBeAg to anti-HBe and HBsAg to anti-HBs (21 men, 13 women and 3 boys, mean age of adults 44 years). During the 8-years investigation period seroconversion of HBeAg occurred in 19 of 37 patients (51.3%) which is an annual rate of seroconversion 6.4%. HBeAg disappeared from serum after a mean period of 82 months (range 29-228 months). After seroconversion of HBeAg the ALT and AST activity declined significantly. Acute exacerbation of hepatitis before seroconversion of HBeAg was recorded in 13 of 37 patients (35%). The mean ALT activity at the peak of exacerbation was 7.93 mu kat/l, the average duration of exacerbation was 9.8 months. Seroconversion of HBsAg occurred in 7 of 37 patients (19%). The mean annual rate of seroconversion of HBsAg was 2.4% after an average period of 98 months. During the investigation period 7 patients died (19%), four of them had a constantly positive HBeAg. The authors conclude that very low annual average seroconversion of HBeAg (6.4%) and HBsAg (2.4%) in patients with chronic hepatitis B is probably caused by previous glucocorticoid treatment. PMID- 7992020 TI - [Perianal disease in Crohn disease]. AB - The treatment of perianal disease by Morbus Crohn belongs to a general conceptional therapy of this disease and requires close cooperation between gastro-enterologist and surgeon. Primary role in the treatment belongs to the internist, surgeon intervenes only in case of complications or during failure of the conservative treatment. Simple, asymptomatic fistulas are treated conservatively. The fistulas with trouble requires local surgical treatment. In case complicated, multiplied of the fistulas is indicated curative resection of the bowel, if it is indicated from another reasons, in dependence on classical criterions. Temporary derivative colostomy is applied in case, where curative resection is not indicated or if the rectum is not affected or if curative resection and local surgical treatment were ineffective. Proctectomy is applied only during massive affection of rectum and destruction of spincters. Our work confirms that the mentioned surgical methods in treatment of perianal disorder accompanying Morbus Crohn are still valid and the improvement of results in treatment this disease could be expected rather on the field of farmacotherapy. PMID- 7992021 TI - [Prevention of thromboembolic disease using mini doses of heparin in surgery patients]. AB - In our study, the effect of the prophylaxis with the low doses of heparin on the occurrence of the deep venous thrombosis or the thromboembolic disease (TED) in the selected groups of the patients was investigated. From our work arises that the patients suffering from malignant diseases are actually at the high risk according to the shortened values of APTT in the preoperative period, which shows evidence of hypercoagulability and further according to the major occurrence of the deep venous thrombosis and the thromboembolic disease during the insufficient prevention by heparin (II. gr. 12%). Low doses of heparin evidently affected the values of APTT and elevated them to the more desirable levels in most of the patients. During the therapy by heparin is necessary to control regularly the values of APTT and to correct the dosage conditionally. Failure and complications of the therapy by heparin is mostly due to incorrectly dosed heparin or its delayed administration or further its improper and inadequate application in the group of the patients being contraindicated (mainly the patients suffering from the bleeding disorders or hepatic damage). The dosage of heparin must be consistent, then the therapy is safe and effective. At any postoperative complication it is necessary to applicate heparin again in the case of its previous abortion. It is also necessary to monitor the mobility of the patients after the operation, which is individual and according to correct the length of the administration of heparin. The period of the administration of heparin is individual, not overall. It is needless to afraid of the application of heparin in the surgical patients.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7992022 TI - [A new method of retrograde hypothermic cardioplegia]. AB - Application of the cardioplegic solution dramatically improved the results of the operations in ECC. Authors discussed the methods of application of the cardioplegic solution, mainly in the connection with its applications to the sinus coronarius. This is then discussed from another point of view of its use. In the field of the cardioplegy there is referred about new authors' method, and so on the possibility of its use, and the most propriete indications. Described method is available and its parameters, verified clinically and experimentally, are advantageous in the stated situations. PMID- 7992023 TI - [Successful resuscitation and recovery of brain function]. AB - After each circulation block which has been successfully resuscitated comes to post-resuscitation disease the seriousness of which depends on the duration of block. It is a specific pathophysiological condition of vital organs just after the ischemic anoxia. The brain is able to tolerate only four minutes of block without its damage and represents a factor limiting the success of cardiopulmocerebral resuscitation (CPCR). The present researches in resuscitology are concentrated towards the research of the chemical nature of endotoxins created during the ischemic affection of other organs which inflicts inversely the brain. Therefore the recovering of cerebral functions from the arrest of heart activity lasting more than five minutes is always problematic because it is already under the influence of existing changes in organ systems which follow after the reperfusion. PMID- 7992024 TI - [Problems in craniocerebral injuries]. AB - Considering the number of patients hospitalized for craniocerebral injuries, the authors found, that it is the second highest of all wound injuries, and that in the age group to 44 years, these injuries, mostly treated in the surgical departments of hospitals, are also the most frequent cause of death. Both the correct diagnosis and timely cure are essential for lowering the mortality rate and alleviating the post-injury impairment. Even thought inebriety in a larger number of patients makes the diagnosis and treatment difficult, it seems possible that in many other cases shorter hospitalization as well as a treatment on the out-patient basis, mostly by a neurologist, should be considered. This contribution focuses on isolated craniocerebral injuries. In the years 1981-90, this group of patients hospitalized in our department, reached the number 1, 135. Of which 208 (18.3%) suffered the structural damage of the brain tissue diagnosed as cerebral contusion or intracranial bleeding, 927 (81.7%) brain concussion, and 68 (6.0%) simultaneously had polytrauma. PMID- 7992025 TI - Swedish Association of Urology. Proceedings of the annual spring meeting 1994. Malmo, June 1-3, 1994. PMID- 7992026 TI - [AIDS--a leading cause of death among young people in Switzerland]. AB - Analysis of Swiss mortality statistics reveals that from 1980 to 1992 AIDS has become one of the leading causes of death among Swiss women and men aged 25 to 44 years. In 1992 77% (n = 414) of all AIDS-related death cases (n = 540) were in this age group. In the mortality statistics of men aged 25-44 years, AIDS (n = 307; death rate = 27.8/100,000) was found to be in third place after accidents and suicides. Among women aged 25-44 years, AIDS (n = 107; death rate = 9.9/100,000) was second after cancer. In spite of the inadequate epidemiological data position in Switzerland it may be suspected that in a few years AIDS will be the leading cause of death for both sexes in this age group in Switzerland. PMID- 7992028 TI - [Results of liver transplantations in Geneva or 32 consecutive transplantations without mortality in 2 years]. AB - Between 1 january 1992 and 31 december 1993, 32 liver transplantations were performed in 29 patients (5 transplants in 3 children and 27 transplants in 26 adults) at Geneva University Hospital. Despite 5 super-urgent transplantations (3 fulminant hepatitis, 1 end-stage Wilson disease and 1 primary nonfunction), all patients are still alive and all have lived more than 10 months. On 1 october 1994, all patients were at home and 93% were in good general condition. No patient of this series had been transplanted for cancer and all patients positive for hepatitis B surface antigen receive long-term administration of anti-HBs immune globulin: in this respect, the long-term mortality risk of the present series of patients seems to be very low. Although these results highlight that liver transplantation can be performed safely by a competent medico-surgical team, two significant difficulties have to be outlined. First, patients are likely to die on the waiting list due to unavailable grafts, especially in emergency cases. Second, the postoperative period of patients with decompensated end-stage liver disease at the time of liver transplantation is still one of high morbidity. These facts underline that chronic liver disease patient should be evaluated for liver transplantation prior to the terminal decompensated stage of the disease, when the candidate's invariably poor general condition precludes successful liver transplantation. PMID- 7992027 TI - [Can the quality of a modest liver transplantation program compare to international standards? Results in Inselspital Berne]. AB - Today, orthotopic liver transplantation is the treatment of choice for the endstage of various liver diseases, and a 1-year survival rate of over 80% is reported in international surveys. The liver transplant program of the Inselspital is very small compared to international centers and this may raise questions about the results and the justification for such a program. In a 24 month period, 20 liver transplants (including 2 retransplants) have been performed in 18 patients at the Inselspital. 2 patients (11%) died 20 and 268 days respectively after transplantation. 2 patients (11%) had significant morbidity 502 and 529 days respectively after transplantation. After a median follow-up of 11.5 months postoperatively, 14 (80% of all patients) lived an independent life. 9 (50%) were fully reintegrated in the household or in their profession and 5 others (30%) were working part time. We conclude that even a small liver transplant program based only on routine resources can achieve results comparable to international standards. PMID- 7992030 TI - [Annual meeting of the Swiss Society of Intensive Medicine and the Swiss Society of Infectology. Lausanne-Dorigny, 8-9 September 1994. Abstracts]. PMID- 7992029 TI - Pathophysiology of failure to wean from mechanical ventilation. AB - Weaning patients from mechanical ventilation constitutes a major portion of the workload in an intensive care unit, as over 40% of total ventilator time is consumed by the weaning process. Several pathophysiological mechanisms may be responsible for weaning failure, but the precise role of each is incompletely understood. Patients who fail a weaning trial commonly develop hypercapnia, which appears to be due to decreased tidal volume rather than a primary decrease in respiratory drive. Respiratory muscle performance is impaired as a result of dynamic hyperinflation and paradoxic motion of the rib cage and abdomen. Worsening of pulmonary mechanics will cause further embarrassment of the respiratory muscles. However, the clinical importance of respiratory muscle fatigue remains unclear. Afferent stimuli arising in the lung parenchyma, respiratory muscles, or as a consequence of impaired gas exchange will be transmitted to the respiratory control centers and result in severe dyspnea in patients who fail a weaning trial. PMID- 7992031 TI - [59th Annual meeting of the Swiss Society of Gastroenterology and Hepatology in conjunction with study groups on abdominal ultrasonography, enodoscopy and study of the liver. Berne, 15-17 September 1994. Abstracts]. PMID- 7992032 TI - Indoor exposure to perchloroethylene (PCE) in individuals living with dry cleaning workers. AB - Perchloroethylene (PCE) is the most widely used solvent in dry-cleaning; it is toxic to the liver, kidney and central nervous system and may be a human carcinogen. PCE levels in the ambient air of dry-cleaners' homes were measured, and samples of end-exhaled air (alveolar air) from subjects who were not themselves occupationally exposed, but who were members of the household of dry cleaners were compared with samples from the general population. Thirty apartments were visited housing dry-cleaners and their families, and located well away from the dry-cleaning premises. Indoor air samples and alveolar air samples were collected contemporaneously from the dry-cleaners (36) and members of their household (34). The same sampling procedure was followed in 25 private homes where samples of alveolar air were collected from 41 subjects who were not occupationally exposed and who acted as control group. All the samples were analysed by direct-injection gas-chromatography. PCE levels in dry-cleaners' homes proved to be significantly higher than in control houses (geometric means: 265 vs. 2 micrograms/m3, P < 0.001). PCE levels in the alveolar air exhaled by dry-cleaners, their family members and control subjects were statistically different (geometric means: 5140, 225 and 3 micrograms/m3, respectively; P < 0.001). PCE is a ubiquitous substance in indoor air, but is present at higher concentrations in apartments where dry-cleaners and their families live. Biological monitoring of PCE in alveolar air confirms that family members of dry cleaners are more exposed than the general population. PMID- 7992033 TI - Identification of metabolic intermediates in microbial degradation of phenol using laser desorption time-of-flight mass spectrometry. AB - Laser desorption time-of-flight (LD-TOF) mass spectrometry was utilized to determine the metabolic intermediates in microbial degradation of phenol. The identified components were in good agreement with the well-documented pathway. This technique also demonstrated excellent precision. Analytical merits, instrumentation and methodology are discussed. PMID- 7992034 TI - Dental lead levels in the Galician population, Spain. AB - The aim of this study was to investigate tooth lead concentrations in a Spanish population living in Coruna, Spain. A total of 220 teeth were analysed using a microwave oven digestion procedure and lead content was measured by atomic absorption spectrometry. Samples were classified according to age, sex, type of tooth, cause of extraction and place of residence. Tooth lead levels followed a logarithmic-normal distribution. The general geometric mean was 10.36 micrograms/g of tooth. There was a significant increase in teeth lead levels with advancing age. Permanent teeth showed higher values (13.09 +/- 1.07 micrograms/g, mean +/- S.E.M.) than deciduous teeth (3.96 +/- 1.07 micrograms/g). However, no differences were found between sexes. High lead concentrations were detected in pathological teeth, particularly in those with periodontal pathology, suggesting a relation between lead levels and dental disease. Nevertheless, teeth with caries did not show any significant lead increase. People living in urban areas of the coast had the highest lead teeth contamination. This is the first study in Spain which describes the tooth lead levels as a marker of lead exposure. PMID- 7992035 TI - Distribution of cadmium in the food chain (soil-plant-human) of a cadmium exposed area and the health risks of the general population. AB - Since 1960, extensive cadmium emissions from a factory producing fluorescent substances and cadmium pigments resulted in cadmium accumulation in the urban area of Bad Liebenstein. We show cadmium exposure of soils and plants in Bad Liebenstein and the meadows near the Grumbach brook. Lettuce and parsley from Bad Liebenstein contained 6- and 9-fold levels of cadmium (2140 and 1194 micrograms/kg dry matter) when compared with control plants. Vegetables from gardens in the immediate vicinity of the Grumbach brook contained cadmium levels which partly exceeded the limit values of the Federal Office of Health. The cadmium status of the inhabitants of Bad Liebenstein was tested by means of hair, whole blood and urine samples. The values were within the normal range (389 micrograms/kg dry matter hair; 1.06 micrograms/l whole blood; 0.24 microgram/l urine). In a duplicate study, the cadmium intake amounted to 10 micrograms/day in men and to 9 micrograms/day in women, which is only 12 or 15% of the WHO limit value. Hence, it follows that the cadmium exposure of soils and flora is not reflected in the food chain of the inhabitants of Bad Liebenstein and health risks caused from cadmium can be excluded. PMID- 7992036 TI - Comparative study of two in vitro models (L-929 fibroblasts and Tetrahymena pyriformis GL) for the cytotoxicological evaluation of packaged water. AB - The preservation of 234 samples of water packaged in polychloride vinyl (PVC), polyethylene terephthalate (PET) and glass-bottles was concurrently evaluated using both classical chemical analysis oriented to finding organic and inorganic substances which could have been leached by the packaging and in vitro toxicological bioassays using two models: the L-929 established cell line of fibroblasts and the ciliated protozoa Tetrahymena pyriformis GL. Although no significant abnormality was detected with the chemical analysis, cytotoxicity was detected with both models in some samples of water bottled for > 18 months, for either PVC, PET or glass-packaging. However, statistical analysis did not allow a mathematical relationship between the cytotoxic effects, the length of storage and the packaging to be demonstrated. PMID- 7992037 TI - Plague vaccine "regulations": ensuring quality. PMID- 7992038 TI - EPA dioxin reassessment. PMID- 7992039 TI - Thailand to test controversial vaccine. PMID- 7992040 TI - Human embryo research. Clinton rules out some studies. PMID- 7992041 TI - Freedom of information. Washington law forces grant disclosure. PMID- 7992042 TI - Science education. National standards finally ready for public scrutiny. PMID- 7992043 TI - The Duesberg phenomenon. PMID- 7992044 TI - Duesberg and critics agree: hemophilia is the best test. PMID- 7992045 TI - Fulfilling Koch's postulates. PMID- 7992046 TI - The epidemic in Thailand. PMID- 7992047 TI - Could drugs, rather than a virus, be the cause of AIDS? PMID- 7992048 TI - Scientists and the integrity of research. PMID- 7992049 TI - Binding site revealed of nature's most beautiful cofactor. PMID- 7992050 TI - How a protein binds B12: A 3.0 A X-ray structure of B12-binding domains of methionine synthase. AB - The crystal structure of a 27-kilodalton methylcobalamin-containing fragment of methionine synthase from Escherichia coli was determined at 3.0 A resolution. This structure depicts cobalamin-protein interactions and reveals that the corrin macrocycle lies between a helical amino-terminal domain and an alpha/beta carboxyl-terminal domain that is a variant of the Rossmann fold. Methylcobalamin undergoes a conformational change on binding the protein; the dimethylbenzimidazole group, which is coordinated to the cobalt in the free cofactor, moves away from the corrin and is replaced by a histidine contributed by the protein. The sequence Asp-X-His-X-X-Gly, which contains this histidine ligand, is conserved in the adenosylcobalamin-dependent enzymes methylmalonyl coenzyme A mutase and glutamate mutase, suggesting that displacement of the dimethylbenzimidazole will be a feature common to many cobalamin-binding proteins. Thus the cobalt ligand, His759, and the neighboring residues Asp757 and Ser810, may form a catalytic quartet, Co-His-Asp-Ser, that modulates the reactivity of the B12 prosthetic group in methionine synthase. PMID- 7992051 TI - Polyglycylation of tubulin: a posttranslational modification in axonemal microtubules. AB - A posttranslational modification was detected in the carboxyl-terminal region of axonemal tubulin from Paramecium. Tubulin carboxyl-terminal peptides were isolated and analyzed by Edman degradation sequencing, mass spectrometry, and amino acid analysis. All of the peptides, derived from both alpha and beta tubulin subunits, were modified by polyglycylation, containing up to 34 glycyl units covalently bound to the gamma carboxyl group of glutamyl residues. This modification, present in one of the most stable microtubular systems, may influence microtubule stability or axoneme function, or both. PMID- 7992052 TI - Phylogeny of the attine ant fungi based on analysis of small subunit ribosomal RNA gene sequences. AB - Complete 16S-like ribosomal RNA coding regions were obtained from the fungal symbiont of five genera of attine (leaf-cutting) ants and two free-living fungi. Phylogenetic analyses with distance matrix, maximum likelihood, and parsimony methods revealed that the attine fungal symbionts are homobasidiomycetes in the order Agaricales. Comparison of the topology of the attine fungal symbiont phylogenetic tree with a tree based on attine ant morphology revealed a congruent branching pattern of the more derived attine ants and their fungal symbionts. The parallel branching pattern suggests a long-term coevolution of derived leaf cutting attine ants and their fungal symbionts. PMID- 7992053 TI - Naturally occurring variation in bristle number and DNA polymorphisms at the scabrous locus of Drosophila melanogaster. AB - The association between quantitative genetic variation in bristle number and molecular variation at a candidate neurogenic locus, scabrous, was examined in Drosophila melanogaster. Approximately 32 percent of the genetic variation in abdominal bristle number (21 percent for sternopleural bristle number) among 47 second chromosomes from a natural population was correlated with DNA sequence polymorphisms at this locus. Several polymorphic sites associated with large phenotypic effects occurred at intermediate frequency. Quantitative genetic variation in natural populations caused by alleles that have large effects at a few loci and that segregate at intermediate frequencies conflicts with the classical infinitesimal model of the genetic basis of quantitative variation. PMID- 7992054 TI - RNA14 and RNA15 proteins as components of a yeast pre-mRNA 3'-end processing factor. AB - Most eukaryotic pre-messenger RNAs are processed at their 3' ends by endonucleolytic cleavage and polyadenylation. In yeast, this processing requires polyadenylate [poly(A)] polymerase (PAP) and other proteins that have not yet been characterized. Here, mutations in the PAP1 gene were shown to be synergistically lethal with previously identified mutations in the RNA14 and RNA15 genes, which suggests that their encoded proteins participate in 3'-end processing. Indeed, extracts from ma14 and rna15 mutants were shown to be deficient in both steps of processing. Biochemical complementation experiments and reconstitution of both activities with partially purified cleavage factor I (CF I) validated the genetic prediction. PMID- 7992055 TI - Control of kinetic properties of AMPA receptor channels by nuclear RNA editing. AB - AMPA (alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid) receptor channels mediate the fast component of excitatory postsynaptic currents in the central nervous system. Site-selective nuclear RNA editing controls the calcium permeability of these channels, and RNA editing at a second site is shown here to affect the kinetic aspects of these channels in rat brain. In three of the four AMPA receptor subunits (GluR-B, -C, and -D), intronic elements determine a codon switch (AGA, arginine, to GGA, glycine) in the primary transcripts in a position termed the R/G site, which immediately precedes the alternatively spliced modules "flip" and "flop." The extent of editing at this site progresses with brain development in a manner specific for subunit and splice form, and edited channels possess faster recovery rates from desensitization. PMID- 7992056 TI - Light-regulated translation of chloroplast messenger RNAs through redox potential. AB - Translation of key proteins in the chloroplast is regulated by light. Genetic and biochemical studies in the unicellular alga Chlamydomonas reinhardtii suggest that light may regulate translation by modulating the binding of activator proteins to the 5' untranslated region of chloroplast messenger RNAs. In vitro binding of the activator proteins to psbA messenger RNA and in vivo translation of psbA messenger RNA is regulated by the redox state of these proteins, suggesting that the light stimulus is transduced by the photosynthesis-generated redox potential. PMID- 7992057 TI - Differential activation of ERK and JNK mitogen-activated protein kinases by Raf-1 and MEKK. AB - Growth factors activate mitogen-activated protein kinases (MAPKs), including extracellular signal-regulated kinases (ERKs) and Jun kinases (JNKs). Although the signaling cascade from growth factor receptors to ERKs is relatively well understood, the pathway leading to JNK activation is more obscure. Activation of JNK by epidermal growth factor (EGF) or nerve growth factor (NGF) was dependent on H-Ras activation, whereas JNK activation by tumor necrosis factor alpha (TNF alpha) was Ras-independent. Ras activates two protein kinases, Raf-1 and MEK (MAPK, or ERK, kinase) kinase (MEKK). Raf-1 contributes directly to ERK activation but not to JNK activation, whereas MEKK participated in JNK activation but caused ERK activation only after overexpression. These results demonstrate the existence of two distinct Ras-dependent MAPK cascades--one initiated by Raf-1 leading to ERK activation, and the other initiated by MEKK leading to JNK activation. PMID- 7992058 TI - Suppression of hyphal formation in Candida albicans by mutation of a STE12 homolog. AB - A Candida albicans gene (CPH1) was cloned that encodes a protein homologous to Saccharomyces cerevisiae Ste12p, a transcription factor that is the target of the pheromone response mitogen-activated protein kinase cascade. CPH1 complements both the mating defect of ste12 haploids and the filamentous growth defect of ste12/ste12 diploids. Candida albicans strains without a functional CPH1 gene (cph1/cph1) show suppressed hyphal formation on solid medium. However, cph1/cph1 strains can still form hyphae in liquid culture and in response to serum. Thus, filamentous growth may be activated in C. albicans by the same signaling kinase cascade that activates Ste12p in S. cerevisiae; however, alternative pathways may exist in C. albicans. PMID- 7992059 TI - Dating hominid sites in Indonesia. PMID- 7992060 TI - Chemotherapy with Platinum Compounds: Current Status and Future Directions. Volume 3: Dosing, Head and Neck Cancer, Genitourinary Cancer, Pediatric Cancer, Tumor of Unknown Origin, Dose Intensity, Future Directions. Kona, Hawaii, February 24-28, 1993. PMID- 7992061 TI - Salvage chemotherapy for recurrent germ cell cancer. AB - Clinical trials of chemotherapy in germ cell cancer have explored the full range of the relationship of chemotherapy dose and intensity. In good-risk patients, successful efforts have diminished the duration of treatment or number of drugs required to reliably cure the illness. In patients with a poor prognosis, efforts to intensify therapy have been undertaken. In the setting of disease recurrence after primary chemotherapy, the outlook is considerably less hopeful, as only 20% to 30% of patients survive recurrent illness. Current standard treatment in this setting is combination therapy with ifosfamide and cisplatin, given with either etoposide or vinblastine. High-dose chemotherapy with bone marrow or peripheral blood stem cell support can cure a small portion of selected patients with multiple recurrences of germ cell cancer. The impact of earlier treatment with high-dose chemotherapy (either as initial salvage therapy or primary treatment) is less certain. Clinical trials in these settings have not yet demonstrated a definite advantage over less toxic conventional-dose therapies. PMID- 7992062 TI - Cisplatin: the future. AB - Cisplatin is one of the most important anticancer drugs yet developed. It proved critical in the development of curative programs for testicular cancer and in life-prolonging regimens for such diseases as small cell lung cancer, ovarian cancer, and metastatic bladder cancer. Cisplatin currently remains the recommended agent of choice for treatment of several malignancies and is a major reagent in the design of existing clinical trials. Although its analogue, carboplatin, has a constitutional and nonhematologic toxicity profile clearly superior to that of cisplatin, thrombocytopenia associated with carboplatin remains a problem, particularly since it can only be circumvented by means of cellular support, with or without growth factors. Continued laboratory investigations exploring new hypotheses concerning the pharmacodynamics of platinating agents emphasize the importance of the parent compound as well. Thus, in the short term, cisplatin will continue to be used in the therapy of certain major cancers. Ultimately, however, it will be replaced by compounds that both obviate its toxicity and increase its spectrum of activity. PMID- 7992063 TI - The future role of carboplatin. AB - In the nonprotocol, clinical arena, carboplatin is supplanting cisplatin due to its more favorable toxicity profile and lower overall cost. A review of the presentations from "The Role of Platinum Compounds in Cancer Treatment" (February 24 to 28, 1993, Kona, Hawaii) suggests that carboplatin can replace cisplatin for dose-intensification studies and treatment of ovarian cancer. Carboplatin (rather than cisplatin) is recommended for chemotherapy of palliative or noncurative intent (ie, for most solid tumors where cisplatin has activity), for the reasons mentioned above. In potentially curative settings (eg, testicular cancer) and in combination with radiation, results obtained with carboplatin are less clear and further study will be required. PMID- 7992064 TI - Cisplatin combinations in the treatment of head and neck cancer. AB - Most patients with head and neck cancers present with locally advanced (stages III and IV) disease. The conventional treatments for these patients are surgery and/or radiotherapy, and the overall results in resectable or unresectable disease are poor and unacceptable. Most of the patients have locoregionally recurrent disease. These poor results led to the investigation of systemic chemotherapy as part of the combined modality treatment for patients with locally advanced head and neck cancers. The achievements of systemic chemotherapy are summarized herein. For instance, active agent(s) and combinations have been identified, as have prognostic factors that influence response rates (overall and complete), and overall results in previously untreated patients. Identification of timing and sequence of chemotherapy as part of combined modality treatment, especially in patients with resectable cancer, has become feasible. Also possible is the prediction of response to subsequent radiotherapy after response to initial induction chemotherapy. This article also discusses the results obtained with concurrent high-dose cisplatin and radiotherapy as total treatment for patients with nasopharyngeal carcinomas and other patients with inoperable and unresectable cancer or in postoperative patients. Results of systemic chemotherapy in laryngeal function preservation is also summarized. Results are also obtained in unresectable patients and organ preservation with induction chemotherapy followed by concurrent chemoradiotherapy. Improved treatment of systemic metastasis and/or survival with maintenance chemotherapy are goals of current trials. We found a decreased incidence of systemic recurrence to be possible with induction and postsurgery chemotherapy. Continued studies are necessary to further improve prognoses in the treatment of head and neck cancers. PMID- 7992065 TI - Chemoradiotherapy for the treatment of regionally advanced head and neck cancers. AB - Despite the use of aggressive surgery and radiotherapy, patients with locoregionally advanced squamous cell carcinoma of the head and neck continue to suffer poor local control and poor survival. Chemotherapy produces excellent regressions of locoregional disease when given as part of initial induction therapy. The use of chemoradiotherapy for regionally advanced disease offers the possibility of organ preservation and retention of organ function for many of these patients. Randomized studies have suggested that chemoradiotherapy also offers better local control and survival than radiotherapy alone. Many chemotherapy regimens used in modern chemoradiotherapy include cisplatin. Because of its ease of outpatient administration, lesser degree of nausea and vomiting, reduced nephrotoxicity, improved nutritional status during therapy, and predictable myelotoxicity, carboplatin has important advantages over cisplatin. Carboplatin possesses well-defined single-agent activity against head and neck cancers, and produces excellent responses in combination with 5-fluorouracil in previously untreated patients. Sequential studies at the University of Maryland Cancer Center showed that weekly carboplatin could be safely and easily combined with standard doses and fractions of radiotherapy. With this regimen, 57% of the patients achieved a complete response and 21% achieved a partial response. Although the addition of bleomycin to this regimen proved somewhat toxic, concurrent carboplatin and radiotherapy allows for the further testing of new agents in developing a combination chemotherapy/concurrent radiotherapy program. Such regimens may improve local control and survival, and may be developed further for organ preservation studies. PMID- 7992066 TI - Carboplatin and radiotherapy in the treatment of head and neck cancer: six years' experience. AB - Between 1987 and 1991, 103 patients with advanced head and neck carcinoma were treated with radiochemotherapy plus carboplatin. Tumors were located in the oral cavity in 33 patients, the oropharynx in eight, and the hypopharynx in seven. Four patients had a tumor of the epipharynx and three, tumor of the larynx. In 48 patients tumor involvement included two or more compartments. Radiotherapy was performed with cobalt-60 rays or 8-MeV photons in a fractionation of 5 x 2 Gy/wk to a dose of 50 Gy. Carboplatin 60 to 70 mg/m2/d was administered days 1 through 5 and 29 through 33. For inoperable patients radiotherapy was continued to a dose of 70 to 74 Gy. To date, 103 patients have entered the study and 100 have completed treatment; three patients died during the treatment period. Actuarial 1 and 2-year survival rates are 77% and 53%, respectively, for all patients; comparable figures for patients with interposed surgery are 93% and 69%, and for the patients treated with radiotherapy alone, 71% and 47%. In a pilot study conducted between 1990 and 1991, 15 patients with advanced head and neck carcinomas underwent hyperfractionated accelerated radiotherapy (2 x 1.6 Gy/d 5 days per week; total dose, 64 to 67.2 Gy) and simultaneous intravenous carboplatin (60 mg/m2, days 1 through 5 and 29 through 33). Eleven patients had T4 and four had T3 tumors. At the end of the treatment period, 12 patients had achieved a complete tumor remission and all others attained a partial tumor involution. Although acute side effects were more pronounced compared with conventional irradiation, this treatment regimen is feasible and the initial complete remission rate of 80% is encouraging. As a result of the encouraging results achieved with hyperfractionated accelerated radiotherapy, we initiated a multicenter randomized study in November 1991. Patients with advanced head and neck carcinomas are either randomized for conventional radiotherapy plus carboplatin or hyperfractionated accelerated irradiation plus carboplatin. As of July 1994, 178 patients have been entered in the study. Results will be evaluated after the study is completed. PMID- 7992067 TI - Platinum-based chemotherapy for bladder cancer. AB - The majority of patients with advanced urothelial cancer are not cured by surgery or radiotherapy. This report reviews the results of radiation and surgery in the treatment of this malignancy and puts advances that have been made with chemotherapy into this context. PMID- 7992068 TI - Etoposide plus carboplatin or cisplatin in good-risk patients with germ cell tumors: a randomized comparison. AB - Two hundred sixty-five evaluable patients were randomized to receive either carboplatin/etoposide (131 patients) or cisplatin/etoposide (134 patients). Among the carboplatin-treated patients, 115 (88%) achieved a complete remission, compared with 121 (90%) of patients receiving cisplatin. In the carboplatin group, however, 16 patients (12%) relapsed following complete remission, in contrast to four (3%) of those receiving cisplatin. Thus, the total number of unfavorable events (incomplete response + relapse) was 32 (24%) in the carboplatin arm, compared with 17 (13%) in the cisplatin arm (P = .02). In addition, patients receiving carboplatin had a greater likelihood of being hospitalized for neutropenia and fever (P = .016) and had lower platelet nadirs (P < .001). It was concluded that carboplatin administered at the dose and schedule used in this clinical trial resulted in an inferior event-free survival rate and worse toxicity than cisplatin, and is not recommended for use in general practice. PMID- 7992069 TI - Carboplatin in pediatric malignancies. AB - Carboplatin is an analogue of cisplatin, an agent that has found application in the cancers that afflict more than one half of children with malignancy. Exploration of the potential of cisplatin has been impeded by its severe and persistent ototoxicity and nephrotoxicity and its prolonged emetogenicity. At conventional doses, carboplatin appears to have a similar spectrum of activity. Its toxicity profile is limited largely to myelosuppression, which may be predicted with some precision from drug dose and glomerular filtration rate, and can be ameliorated with cytokine or bone marrow rescue. Cisplatin nephrotoxicity and especially ototoxicity have been less amenable to amelioration. Unlike cisplatin, carboplatin has demonstrated activity in adult acute myeloblastic leukemia. Exploration of carboplatin proceeds in the setting of bone marrow or cytokine rescue, in combination with nephrotoxic drugs like ifosfamide, in children with brain tumors who are especially susceptible to ototoxicity and in children with acute leukemia. PMID- 7992070 TI - Modeling toxicity and response in carboplatin-based combination chemotherapy. AB - Data from women with advanced ovarian cancer (International Federation of Gynecology and Obstetrics stage III or IV) were analyzed to evaluate the pharmacokinetic/pharmacodynamic relationships of carboplatin-based combination chemotherapy. With the equation area under the plasma concentration versus time curve (AUC) = dose/(creatinine clearance + 25), carboplatin AUC was calculated in each of up to six treatment cycles in 224 women with advanced ovarian cancer who had been randomized to receive carboplatin 300 mg/m2 plus cyclophosphamide 600 mg/m2. In addition, for each patient, the predicted nadir count (obtained by rearranging the University of Maryland single-agent carboplatin dosing formula) was compared with the actual observed nadir count, received and relative received dose intensities were calculated, and carboplatin exposure intensity was defined. Relationships were sought between these treatment indices and the clinical outcomes of time to progression and survival. When combined with cyclophosphamide 600 mg/m2, any carboplatin AUC was found to be associated with greater myelotoxicity and a higher likelihood of both leukopenia and thrombocytopenia occurring than had been determined for single-agent carboplatin. Furthermore, the platelet nadir in 83% of patients was equal to or below that predicted to result from the same dose of single-agent carboplatin. There was a relatively narrow range of received dose intensities within this patient population, but carboplatin exposure intensity was calculated as being distributed over a two fold range within the population. Therefore, received carboplatin dose intensity underestimates the range of plasma drug exposure associated with a fixed dosing regimen of carboplatin. However, there were no consistent relationships between received dose intensity, relative received dose intensity, or carboplatin exposure intensity and the clinical outcomes of time to progression or survival. The relationships between carboplatin exposure and the pharmacodynamic measures of toxicity and response are likely to require definition in each regimen that includes carboplatin and for each tumor type treated. PMID- 7992071 TI - Poorly differentiated carcinoma or adenocarcinoma of unknown primary site: long term results with cisplatin-based chemotherapy. AB - Cases of poorly differentiated carcinoma and poorly differentiated adenocarcinoma of unknown primary site represent a large minority of patients with carcinoma of unknown primary site and are clinically distinct in several ways from well differentiated adenocarcinoma. Cisplatin-based combination chemotherapy produces meaningful clinical responses in more than 50% of the poorly differentiated histologies, and there is a potential for cure in some of these patients (10% to 15%). Clinical and pathologic features enable us to identify many of the patients with responsive tumor types. It is hoped that the future will brighten for these patients as the prospects of genetic diagnosis and treatment become more realistic, and the therapy of common epithelial neoplasms becomes more successful. PMID- 7992072 TI - High-dose ifosfamide/carboplatin/etoposide with autologous hematopoietic stem cell support: safety and future directions. AB - Agents with broad cytotoxic activity, steep linear log dose-response relationships, relative non-cross-resistance, and nonoverlapping nonhematologic toxicities can be combined to create new high-dose combination regimens. We have previously reported phase I dose-escalation studies of ifosfamide, carboplatin, and the combination of the two. Etoposide has reported synergism with these alkylators and produces mucositis as its dose-limiting toxicity. The current study was designed to define the maximum tolerated doses of high-dose combination ifosfamide/carboplatin/etoposide (ICE), with stem cell support for amelioration of hematologic toxicity. Forty-eight adults with advanced malignancy received ICE chemotherapy by 96-hour continuous infusion. Initially, etoposide was added to fixed-dose ifosfamide and carboplatin, then the maximum tolerated dose of etoposide was fixed while doses of the alkylators were individually escalated. Autologous marrow, with or without peripheral blood progenitor cells, was reinfused 3 days after completing chemotherapy. The maximum tolerated doses of ifosfamide, carboplatin, and etoposide were identified as 16 g/m2, 1.8 g/m2, and 1.2 g/m2, respectively. Mortality was 4%. Patients who had prior cisplatin exposure were at increased risk for renal toxicity. If serum creatinine levels (monitored twice daily) rose sharply during chemotherapy, ifosfamide and carboplatin were immediately stopped. Severe multiorgan toxicity developed in the few patients who experienced early renal toxicity. Early stopping enhanced the safety of this regimen. Interpatient differences in chemotherapy drug metabolism or reduced renal clearance may predispose individuals to severe toxicity by increasing overall drug exposure. It was concluded that the ICE regimen is well tolerated and warrants further exploration as treatment of patients with small cell lung cancer, ovarian and germ cell carcinomas, and lymphomas in phase II trials. PMID- 7992073 TI - Current status of peripheral blood progenitor cell transplantation. AB - Peripheral blood hematopoietic progenitor cells are primitive cells capable of both self-renewal and terminal differentiation. Cells can be collected in large numbers from the peripheral blood following their stimulation by cytokine administration or during the hematologic recovery phase following chemotherapy administration. Following their collection from the peripheral blood, these cells have been used both as a supplement and an alternative to bone marrow in providing hematologic reconstitution following high-dose chemotherapy and/or radiation. This article describes the biology of these cells, reviews current methods for their acquisition, and discusses the clinical applications in which they have been found useful. PMID- 7992074 TI - Somatostatin and the concept of peptide receptor scintigraphy in oncology. PMID- 7992075 TI - Localization of gastroenteropancreatic neuroendocrine tumors with 111indium pentetreotide scintigraphy. PMID- 7992076 TI - Somatostatin receptor imaging in patients with neuroendocrine tumors: preoperative and postoperative scintigraphy and intraoperative use of a scintillation detector. PMID- 7992077 TI - Gastroenteropancreatic tumor imaging with somatostatin receptor scintigraphy. PMID- 7992078 TI - Somatostatin receptors in neuroblastoma: diagnostic and therapeutic implications. PMID- 7992079 TI - Somatostatin receptor imaging: a new horizon in the diagnostic management of neuroblastoma. PMID- 7992080 TI - The contribution of somatostatin receptor scintigraphy to the diagnosis of recurrent medullary carcinoma of the thyroid. PMID- 7992081 TI - Clinical experience with somatostatin receptor imaging in lymphoma. PMID- 7992082 TI - Influence of isotope dose on somatostatin receptor imaging: when less is better. PMID- 7992083 TI - Medical oncology considerations in patients with metastatic neuroendocrine carcinomas. PMID- 7992084 TI - Essentials of peptide receptor scintigraphy with emphasis on the somatostatin analog octreotide. PMID- 7992085 TI - The role of somatostatin analogs in the control of tumor growth. PMID- 7992086 TI - Listening to people with cancer. AB - Modern oncologic treatment includes prescriptive remedies for patient-defined illnesses as well as physician-defined diseases. To obtain needed information, oncologists must be skilled as discriminative, analytical, supportive, critical, and appreciative listeners. Listening skills help to establish rapport, confirm understanding, and exchange background information. The neuropsychiatric needs of impaired patients and oncologists should be identified and remedied to improve oncologist-patient communication. Improvements in listening skills makes the oncologist's work more meaningful and helps their patients to feel more confident. PMID- 7992087 TI - Collaborative practice in oncology. PMID- 7992088 TI - The dimensions of oncology social work: intrapsychic, interpersonal, and environmental interventions. PMID- 7992089 TI - Procedural control of cancer pain. PMID- 7992090 TI - Symptom control in advanced cancer. AB - Most important is the physician's attitude, energy, and skill focused toward helping the patient through the difficulties in the last weeks of life. Many causes of nausea, dyspnea, and other troublesome symptoms can be effectively treated, and pharmacologic palliation is nearly always possible. A multidisciplinary team (ie, hospice) can help the physician see the whole picture and needs the physician's input to effectively manage physical, psychosocial, and spiritual components of the situation. The physician who attends to his own physical, psychosocial, and spiritual needs will have the stamina and depth of insight to help his patients through these difficult days. They can then complete their lives in the place of their choosing with the comfort and support needed to finish business, address strained relationships, and open to the mysteries of life and death. PMID- 7992091 TI - Psycho-oncology: depression, anxiety, delirium. PMID- 7992092 TI - Rethinking nutritional support of the cancer patient: the new field of nutritional oncology. PMID- 7992093 TI - Cancer rehabilitation. PMID- 7992094 TI - Cancer survivorship: a consumer movement. PMID- 7992095 TI - Innovative treatment strategies for non-Hodgkin's lymphoma and multiple myeloma. AB - Interferon-alfa (IFN-alpha) has been evaluated in non-Hodgkin's lymphoma and multiple myeloma. The preclinical evidence that IFN-alpha has antitumor activity against non-Hodgkin's lymphoma includes genetic deficits in IFN-alpha production in patients with non-Hodgkin's lymphoma, direct antiproliferative effects of IFN alpha in stem cell assays, and beneficial effects of combined IFN-alpha and chemotherapy in experimental models. Interferon-alfa was active in phase I and II studies of patients receiving prior chemotherapy for non-Hodgkin's lymphoma, particularly those with low- to intermediate-grade lymphoma. The results of randomized studies suggest that adding IFN-alpha to chemotherapy as either induction or maintenance therapy may improve the outcome in patients with previously untreated non-Hodgkin's lymphoma. Interferon-alfa also appears to have activity as a single agent in patients with multiple myeloma, and eventually may have a role as maintenance therapy in patients with multiple myeloma. Collectively, these studies reveal a trend toward using IFN-alpha in patients with smaller hematologic tumor burden instead of reserving it as a last-resort measure. PMID- 7992096 TI - Combination of chemotherapy with interleukin-2 and interferon-alfa for the treatment of advanced melanoma. AB - The antitumor activity of available chemotherapy regimens against advanced melanoma is modest. Likewise, the results with biologic response modifiers such as interleukin-2 (IL-2) and interferon-alfa (IFN-alpha), used alone or in combination, also have been disappointing, although some patients experience very durable remissions. However, the combination of cisplatin-based chemotherapy with IL-2 plus IFN-alpha, referred to as biochemotherapy, has shown encouraging preliminary results. Investigators at M.D. Anderson Cancer Center have conducted a series of phase II studies exploring different schedules of chemotherapy administration using a regimen of cisplatin, vinblastine, and dacarbazine (CVD) and IL-2 plus IFN-alpha (biotherapy). Alternating CVD with biotherapy every 6 weeks produced a response rate similar to that obtained by using CVD alone. The administration of biotherapy immediately after CVD followed by a sandwich of biotherapy/CVD/biotherapy appears to be superior to CVD alone. Finally, the administration of biotherapy concurrently with CVD also appears to be superior to CVD alone. Similar results were observed by other investigators using a cisplatin based regimen in combination with IL-2 plus IFN-alpha. The mechanism of antitumor effect of biochemotherapy remains unclear. Preliminary results of laboratory studies performed at M.D. Anderson Cancer Center suggest that the biotherapy may act by enhancing the cytotoxic effect of CVD, possibly by activation of tumor infiltrating macrophages, which release pro-oxidants that affect the DNA repair process of the tumor cells. Collectively, these clinical and laboratory findings indicate that biotherapy may be synergistic with cisplatin-based regimens and that the sequence of administration appears to be important. PMID- 7992098 TI - Use and coverage of novel cancer agents in managed care. AB - Cancer is unique because its management depends on novel therapies to a greater extent than most other diseases. State-of-the-art care requires access to physicians and facilities that specialize in cancer treatment; however, such access may be blocked by the gatekeeper in the managed care setting. One possible solution to this problem lies in the use of specialists to determine access to tertiary care facilities. Managed care facilities also may limit access to the comprehensive drug therapy required by cancer patients, often by restricting off label drug uses. To solve this problem, criteria should be developed for the use of novel cancer therapies, such as whether off-label uses are supported by major medical compendia or peer-reviewed medical literature. Finally, managed care organizations may deny coverage of state-of-the-art care associated with clinical trials, which may limit the patient's ability to participate in clinical trials. Managed care organizations should cover such costs if they meet certain criteria, such as absence of clearly superior treatment. To provide comprehensive, state-of the-art care for cancer patients, managed care organizations and oncologists must collaborate and find solutions to their mutual problems. PMID- 7992097 TI - Use of interferon in the treatment of chronic myelogenous leukemia. AB - In a series of studies spanning 14 years, investigators from M.D. Anderson Cancer Center (Houston, TX) documented the activity of interferon-alfa (IFN-alpha) in chronic myelogenous leukemia (CML). Beginning with partially purified IFN-alpha, we demonstrated that this biologic compound has clinical activity against CML, that some malignancies are resistant to IFN-alpha, and that the effect is selective whereby the malignant clone can be restored to normalcy. These observations were confirmed by us and others when larger quantities of IFN-alpha became available through recombinant DNA technology (rIFN-alpha). In contrast with our experience with chemotherapy, myelosuppression was not required for cytogenetic remission; this dissociation may be the basis for the selectivity of IFN-alpha against CML. Recently, another group demonstrated that patients randomized to receive rIFN-alpha 2a survived longer than those treated with standard hydroxyurea chemotherapy. New tests are needed to identify the subset of patients most likely to benefit from IFN-alpha therapy and to distinguish cytogenetic responders who are truly cured from those with minimal residual disease. PMID- 7992100 TI - Introduction to the symposium on photodynamic therapy. PMID- 7992099 TI - Chemotherapy and bone marrow transplantation in the treatment of chronic myelogenous leukemia. AB - Many therapeutic modalities have been or are being investigated for the management of chronic myelogenous leukemia (CML). Conventional chemotherapy with hydroxyurea or busulfan continues to be the most widely prescribed modality. Recent data suggest that hydroxyurea is preferred over busulfan on the basis of survival rates, particularly among patients who undergo bone marrow transplantation. To improve on responses associated with interferon-alfa (IFN alpha) alone, IFN-alpha has been added to drugs with selective activity against CML. Combining low-dose cytosine arabinoside and IFN-alpha improves outcome in patients with late chronic-phase CML. Preliminary results with homoharringtonine as induction therapy followed by the addition of IFN-alpha as maintenance therapy are also promising in patients with early chronic-phase CML. Enthusiasm regarding allogeneic bone marrow transplantation remains high, but there are problems related to paucity of ideal candidates, controversies regarding optimal timing, and some mortality. Interferon-alfa has been used in the immediate posttransplant period to reverse early cytogenetic relapse in a limited number of patients, which suggests that IFN-alpha also may be useful in preventing relapse in high risk patients. In autologous bone marrow transplantation, there is interest among investigators in reducing the leukemic burden and altering the marrow microenvironment to favor normal hematopoiesis, but the effect of this alternative on survival is not yet known. Results suggest that young patients are candidates for allogeneic bone marrow transplantation, whereas older patients should be offered IFN-based therapy initially. PMID- 7992101 TI - Photodynamic therapy in dermatology with porfimer sodium and benzoporphyrin derivative: an update. AB - Photodynamic therapy (PDT) involves the sequential administration of photosensitizing drugs and light for the treatment of diseased tissue. The first photosensitizer systematically evaluated for PDT was hematoporphyrin derivative (HPD). Porfimer sodium (Photofrin; manufactured by Lederle Parenterals, Carolina, Puerto Rico, under license from Quadra Logic Technologies, Inc, Vancouver, British Columbia, Canada) is a chemically related photosensitizing agent. Preliminary trials suggest a role for PDT in the treatment of primary, recurrent, and metastatic nonmelanoma skin cancers. Both HPD and porfimer sodium appear to be limited by generalized cutaneous photosensitivity, which lasts up to 6 to 8 weeks after administration. Benzoporphyrin derivative (BPD verteporfin; BPD Quadra Logic Technologies, Inc, Vancouver, British Columbia, Canada) is a second generation porphyrin that has shown promise in clinical studies as a safe and effective photosensitizer for PDT of non-melanoma cutaneous malignancies. Benzoporphyrin derivative is activated by a longer, more penetrating wavelength of light than is porfimer sodium, and has a shorter duration of cutaneous photosensitivity following systemic administration. The use of BPD for PDT of nononcologic conditions also had been studied. Recent trials have shown efficacy in the treatment of psoriasis by BPD-sensitized PDT using drug and light doses lower than those used for malignant tumors. PMID- 7992102 TI - Photodynamic therapy of lung cancer. AB - Photodynamic therapy (PDT) has been used investigationally for the treatment of lung cancer since 1980. Following systemic administration of a photosensitizing agent such as porfimer sodium (Photofrin; manufactured by Lederle Parenterals, Carolina, Puerto Rico, under license from Quadra Logic Technologies, Inc, Vancouver, British Columbia, Canada), specialized optical delivery systems are engaged to deliver light of a specific wavelength (630 nm for porfimer sodium) to neoplastic tissue. A promising use of PDT appears to be treatment of early stage lung carcinoma. Phase I-II clinical trials by Hayata's group in Japan showed that for superficial early lung cancer less than 1 cm in surface diameter, complete eradication can be achieved in approximately 90% of cases. Additional phase II III clinical trials have demonstrated an average of 90% complete response rates for superficial tumors less than 1 cm in diameter. Preoperative PDT may be useful for larger neoplasms to reduce tumor burden and potentially lessen the degree of surgery required. At the British Columbia Cancer Agency, 22 patients with 30 radiologically occult cancers were treated with PDT. In contrast to Hayata's studies, most of these patients had rather extensive tumor burden. Thirty percent of the tumors involved two or more bronchi, and more than half of them were greater than 1 cm in surface diameter. Twenty-three percent of the cases were bronchial stump recurrences. In the group of patients with bronchial stump recurrence, although a complete response was obtained with PDT initially, local recurrences occurred in 75% of cases. These results suggest that recurrent tumor in the bronchial stump should not be treated with PDT because of difficulty in delivering light endobronchially to distal tissues. Photodynamic therapy may have a role in the palliation of advanced, inoperable, obstructive bronchial tumors. Phytodynamic therapy in combination with external radiotherapy may produce better local control than external radiotherapy alone in patients with obstructive bronchial cancers. Photodynamic therapy and conventional Nd:YAG laser therapy appear to be equally effective in relieving intraluminal obstruction by tumor. An advantage of PDT for this purpose is longer time to treatment failure; a disadvantage is photosensitization that usually occurs for up to 4 weeks after treatment. In summary, PDT is a promising curative treatment for patients with small early bronchial cancers. PMID- 7992103 TI - Photodynamic therapy and cancer of the esophagus. AB - Esophageal carcinoma usually is diagnosed at an advanced, incurable stage. In patients with good operative risk, surgery is still considered the ideal treatment. Patients with coexisting major medical conditions in whom resective surgery is precluded may benefit from several therapeutic options, including photodynamic therapy (PDT) with porfimer sodium (Photofrin; manufactured by Lederle Parenterals, Carolina, Puerto Rico, under license from Quadra Logic Technologies, Inc, Vancouver, British Columbia, Canada), dilation, thermal destruction, Nd:YAG laser ablation, injection therapy, and placement of prosthetic tubes. Photodynamic therapy with porfimer sodium is thought to have a direct toxic effect on malignant cells via the production of singlet oxygen, which damages the microvasculature of the tumor and renders it ischemic. The 630 nm wavelength used for clinical PDT exhibits the greatest relative degree of light penetration into tissue, with corresponding activation of retained photosensitizer. The efficacy of PDT with porfimer sodium is closely related to stage of disease. It should be emphasized that PDT has been shown to be potentially curative in patients with early, noninvasive tumors of both squamous and glandular (adenocarcinoma) histologies. Eighty-three patients with esophageal carcinoma were treated using PDT. At presentation, 60% of patients had recurrence following previous radiotherapy or chemotherapy. Patients with less advanced disease had a better response to PDT with regard to relief of dysphagia and prolongation of survival. Photodynamic therapy was found to be more useful than Nd:YAG laser therapy for high, upper third lesions, especially circumferential ones. For tumors larger than 8 cm, PDT was twice as effective as Nd:YAG laser therapy in establishing prolonged lumen patency, especially for adenocarcinomas. Photodynamic therapy appears to have the added advantages of fewer treatments and less pain. The role of PDT in gastrointestinal malignancies continues to evolve. PMID- 7992104 TI - The use of photodynamic therapy in bone marrow purging. AB - High-dose chemotherapy and autologous bone marrow transplantation are an effective combination for treating a number of malignant disorders. Clinical trials have demonstrated a potential role for this regimen in the management of acute leukemia and non-Hodgkin's lymphoma. Autologous bone marrow transplantation continues to be limited by high relapse rates, as compared with allogeneic bone marrow transplantation. Two factors are thought to account for this observation. First, autologous transplants lack the immunologic "graft-versus-host" advantage of allogeneic transplants. Second, autologous grafts have the possibility of tumor cell contamination. Methods to reduce tumor cell contamination in autografts include exposure to chemical agents or monoclonal antibodies; long term marrow cultures; and immunologic manipulation, either with immunomagnetic devices or antibody/complement combinations. Photodynamic therapy (PDT) with porfimer sodium (Photofrin; manufactured by Lederle Parenterals, Carolina, Puerto Rico, under license from Quadra Logic Technologies, Inc, Vancouver, British Columbia, Canada) or benzoporphyrin derivative (BPD verteporfin; BPD-MA; BPD Quadra Logic Technologies, Inc, Vancouver, British Columbia, Canada) may be an effective means of purging bone marrow. The ability of malignant cells to selectively accumulate photosensitizing agents may account for efficacy of PDT in bone marrow purging. The efficacy of porfimer sodium and BPD has been evaluated in cell lines known to express multidrug resistance (MDR), and the results compared with corresponding MDR-negative cell lines. Multidrug resistance positive cell lines appear relatively resistant to BPD; porfimer sodium remains active. The reason for the differential effect of MDR positivity on the cytotoxicity of porfimer sodium and BPD is unclear, but is believed to be related to the larger size of the porfimer sodium molecule. Clinical trials evaluating PDT in bone marrow transplantation are under way. PMID- 7992105 TI - Photosensitizers in photodynamic therapy. AB - Photodynamic therapy (PDT) is based on the use of light-sensitive molecules called photosensitizers. Photoactivation causes the formation of singlet oxygen, which produces peroxidative reactions that can cause cell damage and death. Porfimer sodium (Photofrin, manufactured by Lederle Parenterals, Carolina, Puerto Rico, under license from Quadra Logic Technologies, Inc, Vancouver, BC, Canada) is the photosensitizer that has been studied most extensively. Patients generally have to be hospitalized for 2 days prior to light treatment after administration of porfimer sodium; it takes approximately 48 hours after injection to reach optimal concentration in tumor tissue. The tumoricidal capacity of PDT with porfimer sodium is determined in part by the maximum depth of penetration of light having a wavelength of 630 nm. Porfimer sodium causes cutaneous photosensitivity that may last for up to 6 weeks. Benzoporphyrin derivative (BPD verteporfin; BPD-Quadra Logic Technologies, Inc, Vancouver, BC, Canada), another photosensitizer, accumulates more rapidly in tumor tissue, permitting optimal PDT 30 to 150 minutes following intravenous administration. It is rapidly cleared from the body, and skin photosensitivity does not extend beyond a few days. The primary mechanism of action of PDT is related to the selective accumulation of photosensitizers in cancer tissue. Photodynamic therapy also shows promise in the treatment of a number of nonneoplastic conditions, including psoriasis, macular degeneration of the retina, atherosclerotic plaque and restenosis, bone marrow purging for treatment of leukemias with autologous bone marrow transplantation, inactivation of viruses in blood or blood products, and several autoimmune conditions, including rheumatoid arthritis. Physiologic characteristics shared by this disparate group of diseases, and the mechanisms by which they may mediate photoactivation, are discussed. PMID- 7992106 TI - Progressive pseudorheumatoid chondrodysplasia: a report of nine cases in three families. AB - Nine cases of progressive pseudorheumatoid chondrodysplasia in subjects aged 7-60 years are reported. Six of them were members of one large family with several consanguineous marriages. Evaluation of six generations of this family suggested an autosomal recessive mode of inheritance. The presentation of the disease was between the ages of 3 and 8 years with waddling gait and fusiform swelling of the interphalangeal joints of the hands, clinically resembling juvenile rheumatoid arthritis. Most of the other joints become progressively involved, with crippling disability. One of the patients had typical features of Blount disease at presentation. PMID- 7992108 TI - High-resolution magnetic resonance imaging of arthritic pathology in the rat knee. AB - High-resolution magnetic resonance imaging (MRI) has been used to visualise the changes that occur in both soft tissue and bone during antigen-induced, monoarticular arthritis (AIMA) of the rat knee. Extensive optimisation studies were performed in order to minimise the time of the experiments and to maximise both the signal-to-noise ratio and the contrast in the MR images. The study was cross-sectional rather than longitudinal and at each of the 13 time points studied during the progression of the disease, corresponding X-radiographs and histological sections were obtained. Interpretation of the spin echo MR images was aided by the use of chemical shift-selective imaging, magnetisation transfer contrast and relaxation time experiments, as well as by correlation with the histology and X-radiography data. The MR images clearly show invasion of the synovium by an inflammatory pannus which spreads over the articular cartilage and invades the bone, leading to erosion and later remodelling. Two distinct types of bony erosion were observed: focal erosions, especially at the margins of the joint, and subchondral erosions. It is concluded that MRI provides a sensitive, non-invasive method for investigating both early-stage inflammatory changes and late-stage bony changes in the knee joints of the arthritic rat. PMID- 7992107 TI - Annual evaluation of hip joints and hands for radiographic signs of A beta 2M amyloidosis in long-term hemodialysis patients. AB - Radiographs of hand and hip joints of 15 hemodialysis patients taken annually over at least 15 years were evaluated in this retrospective study. We looked for signs of A beta 2M-amyloidosis such as lucencies, erosions, and soft tissue swelling. The femoral head-soft tissue distance (FHSTD) was used to estimate the soft tissue swelling of the hips. The number and size of lucencies, the number of erosions, and the FHSTD increased during dialysis. Both hyperparathyroidism and failure of renal allograft transplantation influenced the development of lucencies and erosions after 15 years. The FHSTD at the start of the dialysis appeared to be an independent prognostic factor for the lucencies of the hips and hands. We conclude that the radiological signs of A beta 2M-amyloidosis are influenced not only by the duration of dialysis, but also by age, failure of renal transplantation, hyperparathyroidism and the FHSTD at the start of dialysis. PMID- 7992109 TI - MR imaging: its role in detecting occult fractures. AB - Magnetic resonance (MR) studies were performed on 30 consecutive patients who continued to be symptomatic despite negative or inconclusive findings on radiographs and other imaging studies including radionuclide bone scans, computed tomography, and/or polytomography. There were 9 men and 21 women, 20-92 years old (mean age 63 years) whose MR studies were done 3-72 h after frank trauma in 22 cases and in another 8 after 1-4 weeks of increasing pain subsequently attributed to trauma or unaccustomed effort. MR studies were performed using 0.5-T (Phillips) or 1.5-T (Phillips, GE) superconductive magnets. Results indicated that: (1) MR images allowed identification of acute fractures in an emergency room setting, as well as subtle subacute or chronic fractures in the context of strong clinical suspicions despite negative or inconclusive radiographs and other subsequently indecisive imaging studies. (2) MR imaging is the most sensitive way of documenting the earliest changes in traumatized osseous and soft tissue structures simultaneously. PMID- 7992110 TI - Osteoarthritis of the knee: correlation of subchondral MR signal abnormalities with histopathologic and radiographic features. AB - Subchondral signal abnormalities are often present on magnetic resonance (MR) images of patients with osteoarthritis, but no study correlating these changes with histopathology has been published. We selected nine consecutive patients with clinical and radiographic diagnosis of moderate to severe osteoarthritis of the knee scheduled to undergo joint replacement surgery, and performed MR imaging and conventional radiographs preoperatively. After surgery, the resected portions of the femur and tibia underwent gross and microscopic examination, and the findings were correlated with the corresponding findings on the imaging studies. Subchondral MR signal abnormalities of the femur or tibia were present in seven of the nine patients, with intermediate signal on T1-weighted images and low or isointense signal on T2-weighted images. The subchondral signal abnormalities were hemispherical in configuration and corresponded predominantly to fibrous tissue replacing the fatty marrow. A component of trabecular thickening was also present. PMID- 7992111 TI - Relation between the finger positions used in the precision and partial power grips and the regional prevalence of osteoarthritis. AB - The correlation between digital flexion angles used in the precision and partial power grips and the reported regional prevalence of osteoarthritis was studied by goniometric measurement of six female subjects using the grips in 40 preselected activities. Normal interphalangeal ranges were determined by goniometric measurement in 20 normal female subjects. Both grips show a highly significant inverse correlation between mean flexion at each joint and the local prevalence of osteoarthritis. The conflict between these data implicating underuse and those supporting the theory of overload can be reconciled by postulating that primary and secondary osteoarthritis arise from different mechanisms. The former may be bifactorial, with incomplete use initiating the process and cartilage loading determining the rate of progress. PMID- 7992112 TI - Bone marrow blood supply in gadolinium-enhanced magnetic resonance imaging. AB - A retrospective study was performed to determine whether bone blood supply can be assessed on gadolinium-enhanced magnetic resonance imaging. Lumbar spine magnetic resonance imaging (MRI) examinations of 49 patients attending for post laminectomy examination were reviewed (30 male, 19 female, mean age 46.4 years, age range 23-84 years). Each study included sagittal T1-weighted spin echo sequences before and after gadolinium administration. Regions of interest were drawn within the L3 vertebral body from a parasagittal slice from each sequence. Signal intensity (SI) values were ascertained and the percentage increase in SI was calculated. For each patient, changes in receiver gain for pre- and post gadolinium images were corrected by an image scaling factor. In all cases, a measurable increase in SI was found (mean 15.3%, range 4.4-55.7) due to bone vascularity. The results give no indication of the quantity or timing of blood supply but provide a basis for further work. PMID- 7992113 TI - Case report 839: Elastofibroma of the right shoulder causing brachial plexus impingement. AB - A case of an elastofibroma in the right scapular region in a 56-year-old woman was reported. The clinical and pathological findings were discussed. The location of this lesion was uncommon. The common sites were mentioned. The differential diagnosis and magnetic resonance findings were also described. PMID- 7992114 TI - Case report 855: Synovial swelling of the elbow extending into the forearm and causing compression of the underlying ulna. PMID- 7992115 TI - Case report 856: Multifocal osteoid osteoma in a 2.5-year-old child. PMID- 7992116 TI - Case report 857: Hereditary symphalangism with carpal and tarsal fusions and deafness. PMID- 7992117 TI - Case report 858: Postradiation osteosarcoma of the patella. AB - A case of postradiation osteosarcoma of the patella in a 54-year-old man was presented. The lesion in the patella was diffuse and highly sclerotic, and was partially radiolucent in radiographs. The whole patella was removed by Miyakawa's method. Diagnostic criteria, clinical features, and radiographic findings of postradiation sarcoma were described. The rarity of osteosarcoma of the patella was emphasized. PMID- 7992118 TI - Case report 859: Massive calcium pyrophosphate dihydrate crystal deposition disease involving the wrist joint. AB - A case of massive calcium pyrophosphate dihydrate crystal deposition disease (MCPDD) is reported. A 41-year-old Japanese man presented with swelling, intermittent pain, and limitation of motion in the wrist. Radiological studies indicated amorphous calcification and bone erosion. MCPDD, although rare, should be included in the list of the differential diagnosis of periarticular calcific diseases. PMID- 7992119 TI - Case report 860: Bacillary angiomatosis of the calcaneum. AB - Bacillary angiomatosis (BA) is newly reported infectious disease observed mainly in HIV-infected patients, caused by a small gram-negative bacillus of the Rochalimea genus. From a purely dermatological presentation similar to that of Kaposi's sarcoma, it may evolve into a systemic disease. Bone lesions seem fairly frequent. We report a case of an isolated osteolytic lesion due to the BA bacillus. PMID- 7992120 TI - Case report 861: Primary lymphedema of the left lower extremity. AB - We believe MR findings to be quite characteristic of primary lymphedema. We believe that MR has a role in diagnosing lymphedema and its complications. PMID- 7992121 TI - Case report 862: Multiple giant cell tumor of bone (symmetrical lesions in both humeral heads). PMID- 7992122 TI - Whither community health workers in the age of structural adjustment? PMID- 7992123 TI - Epidemiology and the web of causation: has anyone seen the spider? AB - 'Multiple causation' is the canon of contemporary epidemiology, and its metaphor and model is the 'web of causation.' First articulated in a 1960 U.S. epidemiology textbook, the 'web' remains a widely accepted but poorly elaborated model, reflecting in part the contemporary stress on epidemiologic methods over epidemiologic theories of disease causation. This essay discusses the origins, features, and problems of the 'web,' including its hidden reliance upon the framework of biomedical individualism to guide the choice of factors incorporated in the 'web.' Posing the question of the whereabouts of the putative 'spider,' the author examines several contemporary approaches to epidemiologic theory, including those which stress biological evolution and adaptation and those which emphasize the social production of disease. To better integrate biologic and social understandings of current and changing population patterns of health and disease, the essay proposes an ecosocial framework for developing epidemiologic theory. Features of this alternative approach are discussed, a preliminary image is offered, and debate is encouraged. PMID- 7992124 TI - The social impact of HIV/AIDS in developing countries. AB - This paper highlights some of the main areas of social impact of HIV and AIDS in developing countries and suggests that these must constitute priority areas for action among international and national policy makers, as well as others concerned with HIV and AIDS. The areas of impact which are considered are: economic and demographic; labour productivity; agricultural production and development; pressures on the health sector; the role of families and households; children; women; HIV/AIDS discrimination; and the impact of HIV/AIDS on the individual. Some of the responses which have already been developed to the impact of HIV and AIDS are considered, and many of these are seen to be at least partially effective ways of addressing some of the consequences of pandemic. The paper concludes however that the escalating cost of HIV and AIDS, in personal, social and economic terms, demands a greater degree of considered, concerted and coordinated action by international, national and local agencies. PMID- 7992125 TI - AIDS and women in Brazil: the emerging problem. AB - This paper compares and problematizes the public discourse on AIDS and sexuality with the actual private discourse of low-income urban women in Brazil. Women's perspectives on sexuality are explored by examining what they say about anal sex, virginity, and fidelity and are seen as approximating culturally scripted ideals for sexual behavior. AIDS discourses that are being proposed by the Brazilian government, Brazilian AIDS activist groups and the women's movement are examined in light of these perspectives. Condom literacy, a central component to the Brazilian AIDS activist campaign, is problematized within the context of low income women's lives. PMID- 7992126 TI - AIDS and the health crisis of the U.S. urban poor; the perspective of critical medical anthropology. AB - The social identity of HIV/AIDS in the U.S. has been shaped, for the most part, by two factors, the prevailing configuration of social relations across class, racial, gender, and sexual orientation, on the one hand, and the prevailing array of public health, especially epidemiological, categories of disease transmission, on the other. Focusing on the AIDS epidemic among inner city people of color, this paper challenges the distortions wrought in our understanding from both of these factors and instead develops an alternative perspective for AIDS research among medical anthropologists and health social scientists generally. PMID- 7992127 TI - Subject, project or self? Thoughts on ethical dilemmas for social and medical researchers. AB - In this paper we address an important but sadly neglected area; namely some of the ethical issues which arise for social and medical researchers in the course of their work. Our concern is for a wide spectrum of researchers using the full range of social research methods from small-scale in-depth qualitative work through to large scale quantitative studies. The unifying factor is that they all have an element of contact and hence the potential for interaction between the researcher and the subject. In our experience (with the exception of some ethnographers) few if any social researchers will have had adequate training about the interactional aspects of their work. As a result they are unprepared for the ethical dilemmas and conflict of loyalties which they might experience. To understand these issues it is important to look at the context within which such research is undertaken. PMID- 7992128 TI - Multi-dimensional interaction analysis: a collaborative approach to the study of medical discourse. AB - This paper reviews the conceptual frameworks of several research approaches to the study of medical interactions. Two methods are discussed: process analysis and microanalysis. Adapted from Robert Bales's study of the behavior of small groups, process analysis sorts and tallies such interviewing processes as questioning and informing, achieving analysis of large numbers of interviews at the expense of attention to the content or context of the interview. When used in medical interaction research, process analysis seeks correlation between processes documented in the interview and outcomes of the interview. The methods of conversation analysts and discourse analysts, microanalyses subject medical conversations to close linguistic study and contextualization. This review focuses on the underlying assumptions, generalizability of findings, and the types of subjective judgment applied by the methods. It then describes the Multi Dimensional Interaction Analysis (MDIA) system, a linguistic analytic instrument that combines features of process analysis and microanalysis to capture content, process, and context of medical conversations. The MDIA's validity and reliability are reported and implications for future research are outlined. PMID- 7992129 TI - The end of the second most expensive health care system in the world: some geographical implications. AB - In Canada, there has been an increasingly, vociferous debate over the future of a health care system which is based on 5 principles: comprehensiveness; public administration; universality; portability; and accessibility. In part, this debate is a policy tug-of-war among provincial governments, special interest groups and the public who on one side want to maintain the principles of the health care system and on the other want to control costs within the system. The outcome of this policy tug-of-war is demonstrated through an analysis of the funding of health care in the province of Ontario, Canada in general, and the closure of hospital beds specifically. The analysis shows that in attempting to restructure the system, rationalization and growing spatial inequality are occurring simultaneously. The analysis calls into question the whole strategy of bed closures as a method of controlling health care costs. These conclusions have implications for other national health care systems where hospital bed closures have also been used as a strategy in controlling health care costs. PMID- 7992130 TI - Self-rated health revisited: exploring survey interview episodes with elderly respondents. AB - Analysing transcripts of survey interview episodes where self-rated health was discussed, the paper aims (1) to throw light on the interview situation and the way in which talk is structured in this situation, and (2) to uncover the elements out of which the interviewees construct their 'health'. The excerpts analysed show that the survey interview is an interactional situation produced by the interpretations and actions of the people involved. As a rule, the interviewees did not simply opt for one of the preset alternative answers but inserted their own descriptions and explanations. In this talk, 'health' appears as a multidimensional, context-bound phenomenon that can be constructed out of different, even contradictory elements. PMID- 7992131 TI - An essay: 'AIDS and the social body'. PMID- 7992132 TI - When 50-50 isn't fair: the case against couple counseling in domestic abuse. PMID- 7992133 TI - Comparison of white and nonwhite homeless men and women. AB - The majority of the homeless population are people of color. There has been little study of racial differences among the homeless population, and racial findings have not been reported separately for homeless men and women. This study investigated differences between white and nonwhite homeless people in a randomly selected sample of 600 homeless men and 300 homeless women in St. Louis. The 900 homeless people were interviewed using the Diagnostic Interview Schedule and Homeless Supplement. About three-fourths of the sample were African Americans. The homelessness of the white people was more often internally related, for example, substance abuse in men and non-substance abuse psychiatric illness in women. The homelessness of nonwhite people was more often externally related, for example, socioeconomic problems caused by lower incomes for men and reliance on a failing welfare system by women and their dependent families. These differences point to potentially divergent emphases for intervention with these subpopulations. Because of the diversity within racial subgroups, however, all need a variety of interventions for both external and internal problems. PMID- 7992134 TI - Self-help strategies and resources among people at risk of homelessness: empirical findings and social services policy. AB - Although studies suggest that informal helping among poor people keeps millions off the streets of America, very little is known about self-help strategies and resources that exist among poor households and their role in the prevention of homelessness. This study examines the characteristics of homeless people who double up with their friends and relatives. It also examines their relationships with those who house them. Survey data revealed differences in the helping strategies and resources of those who double up. The respondents' sex, race, presence of children, and dependence on public assistance appear to influence the opportunities to double up with friends or relatives. Recommendations are made to enhance the living conditions among doubled-up households so they may continue to serve as a foundation in the prevention of homelessness. Although our primary focus is on the homeless population, policy recommendations include ways to help the low-income households that shelter them as well. PMID- 7992135 TI - Homeless children: are they different from other low-income children? AB - This study examines the differences in academic performance, adaptive functioning, and problem behaviors of 145 elementary school-age children who had experienced homelessness and a matched group of 142 mobile children with low socioeconomic status (SES). The Achenbach and Edelbrock Teacher Report Form and the Harter Self-Perception Profile for Children were used. Within groups, children displayed a range of academic and psychological functioning; about 30 percent performed in the normal range. Comparisons revealed no significant differences between homeless and low SES-mobile children. However, the children's scores taken together differed substantially from norms. These findings suggest that although homelessness is a stressful event in children's lives, long-term poverty may be a more appropriate marker of risk in children. Further, the findings imply that interventions must presume a substantial diversity of need within the various populations. A model of the dynamic of poverty, mobility, and lack of social supports is presented. Implications for intervention by schools and community agencies are discussed. PMID- 7992136 TI - Emotional concerns and treatment of male partners of female sexual abuse survivors. AB - Many men are discovering that they are involved with women who were sexually abused as children. However, male partners of female sexual abuse survivors have thus far received little attention in the literature. As these men increasingly seek treatment with concerns of their own, social workers must become familiar with their emotional experiences and treatment needs. This article outlines the major concerns expressed by 20 male partners of sexual abuse survivors. These concerns included conflicts about expressing needs, frustration with various aspects of their relationships, guilt and shame at having feelings, questions about how to deal with relatives, and sexual issues. The author recommends a treatment approach that combines attention to both the individual's and the couple's concerns and uses insight and the safety of the therapeutic relationship to promote growth. The importance of further outreach to partners of women who were sexually abused as children and the need for increased attention to other partner populations are highlighted. PMID- 7992137 TI - A critical analysis of the concept of codependency. AB - This article addresses problems associated with conceptualizing interpersonal behaviors as addictions or diseases and pathologizing characteristics associated with women. The failure of the codependency model to focus on the unequal distribution of power and resources and the blurring of responsibility between the actor and audience are also discussed. Individual identity can be lost in the label, and the codependency model encourages separation from rather than connection with the family of origin. PMID- 7992138 TI - "Shadows of the heart": a dramatic video for the treatment resistance of spouse abusers. AB - Successful intervention with spouse abusers, most of whom are ordered into treatment by the courts, must overcome formidable anger and resistance, often expressed by high attrition and scant participation in the group treatment process. The dramatic video "Shadows of the Heart" dissipates client resistance by providing internal motivation to control violent behavior. The video dramatizes spouse abuse from the viewpoint of a young boy, who as a man has become a spouse abuser. As clients experience compassion for the child witness to family violence, they learn to convert their habitual anger response into nonviolent actions. Developed to combat treatment resistance, the video presentation was tested in a randomized experiment with 106 male spouse abusers drawn from seven public and private agencies. Results indicate that the video presentation significantly increased attendance and participation in the group treatment process. PMID- 7992139 TI - Social services for battered women: are they adequate, accessible, and appropriate? AB - During the past 20 years a network of services, including official state agencies and statewide grassroots domestic violence coalitions, has developed across the country to meet the problem of woman abuse. Although state agencies have gained access to diverse federal funds; have developed additional, more-creative ways to fund programs; and have established regulatory mechanisms to ensure quality of services, respondents agree that the existing services would not have been developed without the committed energy and effective lobbying of grassroots coalitions. However, these coalitions are now struggling with internal conflicts and are concerned that emerging social problems will eclipse them and capture the scant funds available. Without these coalitions, the network of social services may return the problem of woman abuse to the private arena of family life, where it is treated by therapy. This article surveys both state agencies and coalitions and discusses implications for services to abused women. PMID- 7992140 TI - Chipping away at general assistance: a matter of economics or an attack on poor people? AB - Over the past few years, a number of states and localities have restricted or discontinued their general assistance programs. This article describes the political climate that contributed to these general assistance changes and recommends efforts social workers should be making toward reversing this trend. PMID- 7992141 TI - Overcoming obstacles to forming empowerment groups: a consumer advisory board for homeless clients. PMID- 7992142 TI - Designing precise instruments for focused international mental health service research. PMID- 7992143 TI - Statistical methods for measuring outcomes. AB - This issue of the journal concerns promotion of the routine use of outcome measures in clinical practice; the purpose of this particular article, however, is to warn care providers to think very very carefully before routinely using such measures. Just what are the benefits of their use? What are the outcome measures intended to demonstrate? In order to try to convince the reader that there might be real difficulties in the interpretation of the results, the main body of the paper concentrates on the difficulties in the interpretation of data from a structured research project that has been specifically designed to evaluate an innovation in mental health care provision. The difficulties of interpreting haphazardly collected data as part of routine clinical or administrative practice will be far greater. One of the main purposes of an evaluative exercise is comparison: which approach to service provision is the better? If care providers really want to be involved in mental health service evaluation then their time would be much better spent in taking part in a large multicentre trial. PMID- 7992144 TI - Global function scales. AB - There is a close relationship between impairment of global functioning and mental illness. However valid measurement of global functioning is difficult, and there is no perfect scale. The instruments reviewed in this paper illustrate a range of different approaches. Despite the inherent difficulties the measurement of functioning is a critical domain in mental health evaluative research. PMID- 7992147 TI - Social Security Bulletin. Annual statistical supplement, 1994. PMID- 7992148 TI - SAGES presidential address. Society of American Gastrointestinal Endoscopic Surgeons. PMID- 7992146 TI - Instruments measuring family or caregiver burden in severe mental illness. AB - The consequences of psychiatric disorders for family members, usually called family or caregiver burden, have been studied during the last 4 decades. During this period a variety of instruments have been developed to measure the impact of mental illness on family members, but not all instruments have been described systematically in the published literature. The authors review 21 instruments that have been used or developed during the last 10 years, including several that have not previously been reported. The protocols are described in terms of their method and comprehensiveness, precursors and theoretical foundations, and types of psychometric information available. The instruments are assessed for potential use as research tools, and also for application in routine clinical practice. PMID- 7992145 TI - Patients' and relatives' satisfaction with psychiatric services: the state of the art of its measurement. AB - Despite reservations made on its use as a means for evaluating interventions, various findings in the recent literature point to patients' and relatives' satisfaction with psychiatric services as a particularly salient and appropriate measure of outcome and quality. Even though substantial improvements have occurred in the last decade, research in the field suffers various methodological limitations regarding the study design, the instruments' construction and the lack of attention to their psychometric properties. In the last few years the need for research that develops and refines measures of client satisfaction and establishes their psychometric properties has been considered a priority in service evaluation by a growing number of authors. In spite of this, in the mental health field very few validated instruments for the measurement of satisfaction are currently available. The aims of the present paper were: (1) to update work done in the field of satisfaction with mental health services in the last decade; (2) to describe the main instruments currently available to measure patients' and relatives' satisfaction with mental health services; (3) to provide guidelines for the future development of instruments and their use in mental health settings. The author concludes by emphasizing that, in order to make further progress, considerable effort is needed in developing and spreading the use of validated instruments and discouraging the use of ad hoc measures. Comparability between studies should be pursued more vigorously in order allow both the refinement of existing instruments and a better understanding of the theoretical and substantive meaning of satisfaction with psychiatric services. PMID- 7992149 TI - Laparoscopic repair of gastroesophageal reflux disease. Toupet partial fundoplication versus Nissen fundoplication. AB - This report describes our preliminary experience with two surgical laparoscopic fundoplication procedures, the Nissen technique and the Toupet operation, in which the fundal wrap is reduced from 360 degrees to 180-200 degrees. Fourteen patients with symptomatic gastroesophageal reflux disease who were refractory to pharmacologic and medical therapy underwent a laparoscopic Nissen fundoplication; in an additional 14 patients, we performed a laparoscopic Toupet partial fundoplication. Our laparoscopic approach to the two procedures does not differ significantly from the traditional open methods and the effectiveness of the laparoscopic fundoplication procedures appears similar to that of the same conventional techniques. Oral feedings can be resumed on the first postoperative day and patients typically are discharged on the second day after surgery. Operative time for performing the Toupet procedure averaged just approximately 1.6 h and was shorter than that for the Nissen fundoplication, due to the use of a stapler to secure the fundal wrap. Confirming earlier observations, the laparoscopic Toupet 180-200 degrees fundoplication was associated with a lower incidence of postoperative digestive complications, such as dysphagia, than was the laparoscopic Nissen operation. The laparoscopic fundoplication approach offers the advantages of clear visualization, adequate dissection and precise repair, along with the benefits associated with endoscopic surgery: diminished postoperative pain and discomfort, reduced hospitalization, and quicker return to normal activities. Our experience indicates that the Toupet fundoplication may be preferable to the Nissen technique for many patients requiring surgical treatment of their reflux disease. PMID- 7992150 TI - Experimental study of laparoscopic selective proximal vagotomy using a carbon dioxide laser. AB - This study investigated the effectiveness of laparoscopic selective proximal vagotomy using a CO2 laser. Irradiation of the stomach was performed from the serosal aspect using a defocused CO2 laser beam. In the first experiment, the inhibitory effect on cysteamine ulcers in rats was compared between surgical vagotomy and CO2 laser vagotomy using three different irradiation fields. The results suggested that irradiation near the lesser curvature provided sufficient denervation. In the second experiment, CO2 laser vagotomy was performed laparoscopically in dogs. The procedure lasted less than 1 h and a postoperative endoscopic Congo red test confirmed its effectiveness. Subserosal tissues including the vagus nerve branches showed degeneration and were replaced by fibrosis 3 months postoperatively, but the deeper tissues were spared. In conclusion, laparoscopic CO2 laser vagotomy may be as effective for reducing acid secretion as standard surgical vagotomy. Its simplicity and safety suggest that a clinical trial in humans may be warranted. PMID- 7992151 TI - Direct endoscopic percutaneous jejunostomy (EPJ). Clinical results. AB - Direct puncture of the small bowel under endoscopic guidance (direct EPJ) is possible in patients whose stomach has been removed or whose small bowel cannot be punctured by other methods. From January 1990 to June 1992 a total of 39 patients underwent successful direct EPJ at our institution. The indications were malnutrition after partial or total gastrectomy (n = 19), insufficient anastomosis or a stenosis after esophageal resection and esophagojejunostomy (n = 13), esophageal perforation (n = 3), fistulas (n = 2), or severe trauma (n = 2). The tubes were inserted at the bedside under local anesthesia using the string pull-through technique. The procedure was attempted in five other patients but it was technically impossible to insert the tubes in these patients. Postoperative enteral feeding was possible in all 39 patients whose direct EPJ was successful. Complications included tube dysfunction due to plugging and fracture in five patients, pressure-induced enteric ulcers in two, and local infections in three patients. The ulcers and infections were managed conservatively. We conclude that direct EPJ is a safe, effective alternative to surgical catheter-jejunostomy. PMID- 7992152 TI - Accuracy of viscera slide detection of abdominal wall adhesions by ultrasound. AB - Viscera slide is the normal, longitudinal movement of the intraabdominal viscera caused by respiratory excursions of the diaphragm. By detecting areas of restricted viscera slide, ultrasonic imaging was used to identify anterior abdominal wall adhesions prior to laparotomy or laparoscopy. Transcutaneous ultrasound examination was performed on 110 patients. A prediction of adhesions was made for each patient and then compared to the findings during subsequent laparotomy or laparoscopy. Only patients with previous abdominal surgery or history of peritonitis demonstrated adhesions. Sensitivity and specificity of viscera slide ultrasound in predicting adhesions were 90% and 92%. Nine out of 10 false results involved misinterpretation of ultrasound images of the lower one third of the abdomen. Ultrasonic imaging of viscera slide is highly accurate in detecting abdominal wall adhesions. This technique is most useful in guiding the insertion of trocar in laparoscopic surgery, and as a noninvasive method in studying the formation of adhesions. PMID- 7992153 TI - Laparoscopic cholecystectomy. Do preoperative factors predict the need to convert to open? AB - We reviewed our experience with the last 587 laparoscopic cholecystectomies performed between May 1990 and January 1993 to correlate preoperative findings that may predict the conversion of a laparoscopic cholecystectomy to that of an open procedure. The prediction of a need to convert to an open cholecystectomy would allow the surgeon to discuss the higher risk of conversion with the patient and also allow for an earlier intraoperative decision to convert if difficulty was encountered. In addition to routine demographic data, ultrasound reports were available for 526 patients and the following information was recorded: presence of stones, thickened gallbladder wall, common bile duct dilatation, gallbladder sludge, and cystic duct impaction. Overall, a two times higher rate of conversion was found for male patients and patients with a body mass index > 27.2 kg/m2. Additionally, a thickened gallbladder wall on preoperative ultrasound was correlated with a six times higher conversion rate to open cholecystectomy. As expected, the positive intraoperative cholangiogram was associated with a higher incidence of conversion. Additionally, finding a dilated common bile duct on ultrasound was found to be associated with a nearly seven times higher rate of positive intraoperative cholangiogram. No statistical significance was found between conversion and age, previous abdominal operations, the presence of stones, common bile duct dilatation, gallbladder sludge, cystic duct impaction, or a distended gallbladder. Thus, these predictive findings allow the surgeon to preoperatively discuss the higher risk of conversion and allow for an earlier judgment decision to convert if intraoperative difficulty is encountered. PMID- 7992155 TI - Laparoscopic fenestration of a giant simple hepatic cyst. Case report and technical considerations. AB - The management of symptomatic large, simple hepatic cysts has evolved toward the use of wide unroofing or "fenestration" in instances where patients are not rendered asymptomatic by percutaneous aspiration. We report adoption of the technique of fenestration of such hepatic cysts to the laparoscopic route. Laparoscopic fenestration appears able to accomplish all of the aims of transabdominal fenestration in appropriately selected patients. PMID- 7992154 TI - Is immune function better preserved after laparoscopic versus open colon resection? AB - The purpose of this preliminary study was to evaluate immunologic responses to laparoscopic vs standard open colon resection and to evaluate possible mediators of any differences found. Specifically, we compared cortisol levels and delayed type hypersensitivity response after each method of colon resection in a group of 20 pigs. Two groups of 10 animals each were treated in identical fashion including bowel preparation, anesthesia, and postoperative management. The only difference between groups was that one underwent laparoscopic and the other an open colon resection. Blood specimens for cortisol were drawn before, during, and immediately postoperatively as well as at 11 A.M. on postoperative days 1 and 2. All animals had been previously immunized as piglets with Sow Bac-E (Oxford Veterinary, Worthington, MN), an antigen preparation of common pig pathogens. At the conclusion of the operative procedure 0.5 cc of the antigen was injected intradermally on the right forelimb of the animals. At 48 and 72 h postoperatively the largest diameters of induration surrounding the injection site were measured and averaged. Cortisol levels were measured in serum samples by radioimmunoassay (Met-Path, Rockville, MD). Statistical significance was determined by t-test. Results of skin antigen testing showed that the group of pigs that underwent laparoscopic resection had a 20% greater response, 1.54 cm +/ 0.28 cm at 48 h and 1.53 cm +/- 0.18 cm at 72 h. For the open-surgery group results were 1.24 cm +/- 0.26 cm at 48 h and 1.32 cm +/- 0.21 cm at 72 h, P < 0.05 for the difference between groups at both 48 and 72 h.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7992156 TI - Laparoscopic gastric resection for gastric leiomyoma. AB - Less than 2% of gastric neoplasms that are resected surgically are of smooth muscle origin. Gastric leiomyomas are not encapsulated, and the distinction of benign from malignant leiomyoma may be difficult. Some of these tumors manifest malignant behavior. The histological basis for the diagnosis of benign or malignant smooth-muscle tumor is not entirely satisfactory, and misclassification occurs in some cases. The aggressiveness of those tumors reported as malignant is usually low, and the term "malignant leiomyoma" is usually used rather than the more ominous "leiomyosarcoma." A case is presented of a patient with a 4.5-cm leiomyoma of the gastric antrum resected by the laparoscopic approach. Four laparoscopy trocars were used and multiple applications of the Endo-GIA were needed. Satisfactory margins of resection were obtained. The patient made an excellent recovery with minimal pain. She promptly returned to work and full physical activity. PMID- 7992157 TI - Laparoscopic cholecystectomy in pancreas transplant recipients. AB - Laparoscopic cholecystectomy is the treatment of choice for symptomatic cholelithiasis. Since its introduction in 1987, this procedure has been employed with increasing frequency as its safety has been documented in numerous studies. Absolute contraindications to laparoscopic cholecystectomy have become relative contraindications, and patients previously felt to be at excessive risk for laparoscopic cholecystectomy are viewed as patients who may benefit from laparoscopic cholecystectomy. The use of this procedure in patients with comorbid medical conditions has the potential to decrease patient morbidity. Patients who have previously undergone solid organ transplantation and require immunosuppressive therapy are a group of patients who may benefit from laparoscopic cholecystectomy. We report four patients who have previously undergone combined renal and pancreas transplantation who underwent successful laparoscopic cholecystectomy. PMID- 7992158 TI - Laparoscopic repair of incarcerated paraesophageal hernias. AB - Paraesophageal hernias comprise only 2-5% of all hiatal hernias, yet unlike the more common sliding hiatal hernia, paraesophageal hernias are prone to undergo volvulus, with obstruction, ischemia, and gangrenous perforation. Due to their propensity toward calamitous complications, they must be recognized and repaired as expeditiously as possible. Traditionally these hernias have been repaired by either an open transabdominal or an open transthoracic approach. Laparoscopic repair with Nissen fundoplication has already been successfully applied to the repair of the more common sliding hiatal hernia. Described here is the laparoscopic repair of two paraesophageal hernias. The merit of an anti-reflux procedure as part of this repair is discussed. PMID- 7992159 TI - Gallstone shrapnel contamination during laparoscopic cholecystectomy. AB - The fate of lost gallstones in the peritoneal cavity following laparoscopic cholecystectomy is unknown. We report a case of microabscesses and granuloma formation in the peritoneal cavity and abdominal wall caused by infected gallstone shrapnel due to rupture of the gallbladder during extraction. PMID- 7992160 TI - Incarcerated trocar-wound hernia after laparoscopic hysterectomy. Is closure of large trocar fascia defects after laparoscopy necessary? AB - An incarcerated hernia through a 12-mm laparoscopic trocar wound, causing small bowel subobstruction, was diagnosed in a 50-year-old female patient following a laparoscopic hysterectomy 1 month earlier. Trocar-wound hernias causing early postoperative bowel obstruction are very rare. Insertion of trocars at a narrow angle to the abdominal wall may cause larger fascia defects than the actual size of the trocar. Manual examination and closure of large defects, if possible, may prevent such complications. PMID- 7992161 TI - Acute midgut volvulus following laparoscopic cholecystectomy. AB - A case of midgut volvulus forty eight hours following laparoscopic cholecystectomy is reported. PMID- 7992162 TI - Large postoperative umbilical hernia following laparoscopic cholecystectomy. A case report. AB - The authors report a case of large postoperative umbilical hernia following laparoscopic cholecystectomy, which occurred in the early postoperative period despite primary suture of the trocar insertion site. Forced dilation of the fascial layer is proposed as the etiological mechanism. This procedure should be avoided and an accurate and aseptic removal of the gallbladder should be performed in order to prevent risk of abdominal wall weakness and visceral herniation. PMID- 7992163 TI - Laparoscopic resection of pheochromocytoma. AB - The following case report presents the diagnostic procedures, laparoscopic therapy, and postoperative course of a 48-year-old patient with pheochromocytoma. During the previous 15 years, he had occasionally presented with hypertension, intermittent attacks of severe perspiration, and tachycardia; no diagnostic measures were performed at the time. During an ultrasound examination of the abdomen performed due to gastrointestinal complaints, a 5-cm adrenal tumor was discovered incidentally. Further diagnostic procedures then indicated the presence of a pheochromocytoma which was resected laparoscopically. The anesthesia was tolerated well, although isolated systolic blood pressure peaks to 200 mmHg were observed. The laparoscopic tumor resection presented no problems, although identifying the tumor proved to be difficult and resulted in an extended operation time of 4 h and 20 min. The postoperative course was unremarkable. This case report presents our laparoscopic technique and confirms that techniques proven in the "open" resection of a pheochromocytoma can also be utilized in the laparoscopic approach. PMID- 7992165 TI - The lost gallstone. Complication after laparoscopic cholecystectomy. AB - Laparoscopic cholecystectomy has become the treatment of choice for most patients with gallstones. During this procedure it is not uncommon for the gallbladder to be entered inadvertently, spilling gallstones freely into the peritoneal cavity. Finding and removing all of the spilled gallstones can be difficult and time consuming. The natural history of stones left in the peritoneal cavity, outside the gallbladder, bile ducts, or intestine, is not known. This is a case report of a complication related to several gallstones left in the peritoneal cavity after laparoscopic cholecystectomy. An abscess developed around them, which necessitated the drainage of purulent exudate from the right flank 8 months postoperatively. the abscess and sinus tract did not heal until the stones were removed. If possible, all stones should be removed during laparoscopic cholecystectomy to forestall the development of this type of complication. PMID- 7992164 TI - Videolaparoscopic treatment of spleen injuries. Report of two cases. AB - Splenectomy is very frequently used to manage splenic lesions. Nevertheless, spleen-injured patients who have undergone splenectomy are exposed to hyposplenism. Authors report two patients with splenic lesions treated by conservative surgery (with fibrin glue) using the videolaparoscopic method. In both cases the preservation of the spleen was achieved. The conservative treatment allows one to avoid the risk of hyposplenism and the videolaparoscopy provides the possibility to treat the patient with minimal surgical stress. PMID- 7992166 TI - Localization of small intestinal bleeding. The role of intraoperative endoscopy. AB - The preoperative identification of a bleeding site is not always possible, particularly when bleeding originates in the small intestine. Small vascular abnormalities, such as the telangiectatic lesion described in this report, comprise about 40-60% of such cases. Preoperative location using arteriography, radionuclide bleeding scan, and enteroclysis were nondiagnostic. The lesion was demonstrated by intraoperative endoscopy. A segment of small intestine was resected, and the patient made an uneventful recovery. PMID- 7992167 TI - Thoracoscopic esophageal myotomy--a surgical technique for achalasia diffuse esophageal spasm and "nutcracker esophagus". AB - Thoracoscopic myotomy has been performed for diffuse esophageal spasm "nutcracker esophagus" and achalasia. Technical considerations for thoracoscopic long myotomy such as trocar placement, length of myotomy, extent of myotomy distal to the gastroesophageal junction, hiatal closure, fundoplication and degree of esophageal mobilization are discussed. PMID- 7992168 TI - An alternative technique for laparoscopic cholangiography. AB - The current methods utilized for laparoscopic cholangiography involve cystic duct cannulation and present practical difficulties and potential hazards. An alternative method for intraoperative cholangiography is described which is easy, quick, and safe. The Kumar clamp (a gift from Sabi Kumar, M.D.) is placed across the infundibulum. A 23-gauge sclerotherapy needle is introduced through a side port in the clamp and directed into the infundibulum. The cholangiogram is obtained prior to any dissection in the triangle of Calot, thereby avoiding iatrogenic common bile duct injuries due to misidentification of the cystic duct or anomalous anatomy. To date no pathology has been missed and no complications have resulted from this technique. PMID- 7992169 TI - Laparoscopic splenectomy. AB - Laparoscopic splenectomy was attempted in 16 patients and was performed successfully in 13 (81%) patients with the diagnosis of idiopathic thrombocytopenic purpura (ITP), AIDS-related thrombocytopenia, Hodgkin's disease, or lymphoma. The operative time averaged 157 min, and autologous transfusion was required in four patients. The postsurgical stay averaged 3 days in patients with completely laparoscopic splenectomies and 4 days in patients whose spleens were removed through small counterincisions. No major complications secondary to the procedure itself occurred postoperatively. Conversion to open operation was necessary in three (19%) patients because of bleeding or splenomegaly. With careful selection of patients and mastery of the technique, laparoscopic splenectomy can be safely performed on normal or slightly enlarged spleens. The advantages are less pain, shorter hospitalization, and reduced disability as compared to "open" splenectomy. PMID- 7992170 TI - Use of oxidized regenerated cellulose (TC7) to prevent postoperative adhesions in laparoscopic surgery. PMID- 7992172 TI - Feeding gastrostomy. PMID- 7992171 TI - Minimal access surgery--which path to competence? PMID- 7992173 TI - Entrapment neuropathy in laparoscopic herniorrhaphy. AB - In laparoscopic hernia repairs, the staples used to affix prosthetic mesh have resulted in entrapment neuropathies. This paper describes the diagnosis and treatment of nine cases of entrapment neuropathy. Injuries to all the branches of the lumbar plexus, with the exception of the obdurator nerve, have been treated. Generally, the entrapments are self-limiting, but chronic disability requiring surgical intervention can occur. Staple removal and neurolysis controlled the severe, chronic pain of one femoral nerve entrapment. A thorough understanding of the anatomy of these nerves can prevent stapling in the areas of danger and thus greatly reduce the incidence of this complication. PMID- 7992174 TI - The integration of laparoscopy into a surgical residency and implications for the training environment. AB - Although laparoscopic cholecystectomy is now an accepted part of resident training, the impact of operative laparoscopy (OL) upon the residency environment has not been examined in detail. We reviewed the first 3 years' experience with OL and the process by which it was introduced into our residency program. Data were obtained from our prospective computerized surgical laparoscopic registry as well as from a survey conducted midway in this experience. At that time, a questionnaire was sent to current residents in the program and residents who graduated after the inception of the OL program were interviewed by telephone. OL cases increased each year and comprised a progressively greater percentage of total cases. Residents performed over 97% of cases, with attending surgeons as first assistants. Initially, only senior-level residents participated as surgeons; however, after the first year we noted a significant tendency for cases to filter down the ranks. Junior-level residents have already participated in more laparoscopic than open cholecystectomies and expressed considerable concern about training in open procedures. Graduated residents without exception were able to obtain privileges to perform OL without additional training. They did not feel that resident education was compromised by the advent of laparoscopy. Both current and graduated residents considered didactic sessions including animal laboratories and simulators an important part of training.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7992175 TI - Laparoscopic cholecystectomy. The early experience of surgical attendings compared with that of residents trained by apprenticeship. AB - During our first year of laparoscopic surgery, all cases were performed by attending surgeons; resident involvement was confined to camera work and occasionally to acting as first assistant. These residents were PGY3 or -4. During our second year, these same residents, who had learned the craft in the traditional apprenticeship method, on promotion to senior resident functioned as the primary surgeon in laparoscopic cholecystectomy cases, but under very close guidance by the credentialed attending. Ninety-two cases were attempted in the first year and 100 in the second. There were no differences in age, gender, or preoperative symptoms. More than half the patients had at least one co-morbidity in addition to their gallbladder disease. More women had laparoscopic cholecystectomy soon after pregnancy in the second year, but the percent of the patients with previous surgery declined from 21.4% to 5%. There was a threefold increase in the percent of cases performed in less than two hours and there was a significant reduction in hospital length of stay in the second year. Complication rates were similar in the first and second years. Training residents to do laparoscopic cholecystectomy can be done in a traditional residency program provided the attendings are adequately trained. However, the residents need a higher level of skill at this time than was necessary for open cholecystectomy and have to be further advanced in their training in order to perform this operation laparoscopically. PMID- 7992176 TI - Preceptored introduction of laparoscopic techniques for cholecystectomy into a large university-affiliated medical center. AB - Faced with the task of introducing laparoscopic techniques for cholecystectomy into the practice of a large department composed of individuals with varied backgrounds and experience, our surgical staff decided to grant provisional provileges to five surgeons, two from the full-time faculty and three from the community, who had completed a formal course in laparoscopic cholecystectomy. These five surgeons agreed to assist one another through 10 cases a piece before performing any procedures on their own or serving as preceptors for additional surgeons. Other surgeons could obtain credentials for this procedure by satisfying the same course criteria and receiving assistance from one of the five original surgeons during their first 10 cases. In the 14 months after September 1990, 250 laparoscopic cholecystectomies were performed by 19 different attending surgeons at our hospital. One death from hemorrhage (0.4%) and two bile duct injuries (0.8%) occurred in these patients. One of the bile duct injuries occurred after conversion to open cholecystectomy, as did the hemorrhage, which was from a vessel within the parenchyma of the gallbladder bed which rebled even after temporary control through open ligature technique. The second bile duct injury, the result of injudicious application of hemoclips for hemostasis, was minor in degree and the only injury to occur in a procedure conducted exclusively through the laparoscope. This experience demonstrates that laparoscopic techniques can be safely introduced into an environment involving multiple surgeons by adherence to a careful protocol of preceptored assistance. PMID- 7992178 TI - Combined laparoscopic-endoscopic gastrostomy. AB - Since the first report of successful percutaneous endoscopic gastrostomy placement by Gauderer and Ponsky in 1981 [Surg. Gynecol. Obstet. 152: 83-85], many modifications of the original technique have been published. Each reports easier and safer placement of the gastrostomy tube, but all have the same inherent flaw: Access to the gastric lumen is accomplished by a blind needle puncture of the anterior abdominal wall. A new technique, utilizing a newly available microendoscope (Origin Medsystems), is described. Using the microendoscope, direct visualization of the stomach and left upper quadrant of the abdomen allows safer access to the gastric lumen for subsequent tube placement without the need for additional incisions or punctures. The procedure can still be performed with local infiltrative anesthesia and systemic intravenous sedation. PMID- 7992179 TI - Clinical and laboratory evaluation of an electrosurgical laparoscopic trocar. AB - Electrosurgical energy may be utilized as an adjunct to mechanical force for insertion of laparoscopic trocars. The advantage of this approach may be better operator control of insertion, with less risk of intraperitoneal and retroperitoneal injury. To assess the safety and efficacy of electrosurgical trocars, we compared them to mechanical trocars in clinical and animal trials. During 100 trocar introductions in 25 laparoscopic cholecystectomies, insertion force was measured. In contrast to mechanical trocars, which required progressively more force to insert as size increased, electrosurgical trocars required the same low insertion force regardless of size. No wound complications occurred. In animal experiments, wound healing (measured histologically and by bursting strength) was normal and equivalent for mechanical and electrosurgical insertions. We conclude that electrosurgical trocars require less force for insertion and do not impair wound healing. Electrosurgical trocars may thus offer important safety advantages over mechanical trocars. PMID- 7992177 TI - Use of percutaneous endoscopic gastrostomy tubes in burn patients. AB - Alimentation and decompression are imperative to the successful management of the severely burned patient. Utilization of percutaneous endoscopic gastrostomy (PEG) tubes for these purposes has become a proven effective procedure in non-burned patients with few major complications. We retrospectively reviewed placement of PEG tubes in 31 burn patients, some of whom had been admitted with additional diagnoses such as inhalation injury and/or dysphagia. In 90% of our burn patients, the use of PEG tubes was without complication. The placement of PEG tubes through burn wound areas or donor sites added no increase in wound complications. In summary, there was no mortality referable to the use of PEG tubes, there were no major operative or wound complications, and feedings were tolerated well. This study reports on the use of PEG tubes in a regional Burn Treatment Center. It shows that PEG tubes offer safe and effective alimentation and decompression in the management of burned patients. PMID- 7992181 TI - Endoscopic localization of colon cancers. AB - In order to determine the accuracy of endoscopic localization of colon cancers, the endoscopic location was compared to the actual location at the time of operation in 320 patients who underwent resection of intraabdominal colon cancer between 1983 and 1988. The endoscopic location was correct in 86% of the cases. There were 44 endoscopic errors, including seven missed cancers. One-third of all endoscopic errors occurred when the tumor was in the cecum. We conclude that endoscopy is an accurate method of localizing colon cancers. However, with the advent of laparoscopic surgery and the loss of the ability to palpate the colon, the 14% of endoscopic errors take on a greater importance and additional means for localizing tumors should be pursued in selected cases. PMID- 7992180 TI - Laparoscopic Nissen-Rossetti fundoplication. AB - Although antireflux surgery offers very good results and patient's satisfaction, the referral rate to the surgeon remains very low. We present our experience with a less-invasive procedure that would result in minimal pain and very rapid return to normal activities and thus might lead to earlier referral. Fifty-nine patients with documented reflux esophagitis were treated. There were 31 females and 28 males whose age ranged from 27 to 69 years and whose weight varied between 140 and 280 lbs. Pre-op work-up included endoscopy, barium swallow, manometry, and 24 h pH studies. There was no mortality and morbidity was minimal; hospital stay was 2-3 days. Ten patients were lost to follow-up; all the remaining patients are completely asymptomatic, and the patients who had their pre-op work-up repeated showed normal results. Laparoscopic fundoplication seems to be as efficient and safe as the open procedure. PMID- 7992182 TI - Laparocholecystectomy. 6,865 cases from Italian institutions. AB - Data concerning 6,865 laparocholecystectomies have been collected retrospectively from 19 Italian groups. Only 5% of all patients were chosen for open cholecystectomy (OC). Acute cholecystitis was present in 5.6% of laparocholecystectomies (LC). Conversion to laparotomy occurred in 3.1% of patients. Mortality was 0.06%, morbidity 2.53% (general anesthesia complications 0.07%; general complications 0.07%; omphalitis 0.7%; abdominal complications 1.69%). Main duct lesions occurred in 0.26% of the patients, biliary leaks in 0.48%, bleedings in 0.75%, perforations in 0.2%. Data from literature concerning OC are compared to ours: mortality and morbidity have been lowered by LC; general and abdominal-wall complications have been drastically reduced; main duct lesions are not different. PMID- 7992183 TI - Treatment of ovarian dermoid cysts. Place and modalities of operative laparoscopy. AB - The purpose of this study was to discuss the place and the specific modalities of laparoscopic surgery in the management of ovarian dermoid cysts. This retrospective and noncomparative study was carried out in 65 patients who presented dermoid ovarian cyst between January 1986 and December 1990 in our institution. The surgical treatment was performed purely by laparoscopy in 86.2% of the cases (56 patients). The modalities of laparoscopic surgery were as follows: ovariectomy (8 cases; 14.3%), transparietal cystectomy (4 cases; 7.1%) and intraperitoneal cystectomy (44 cases; 78.6%). In 15 cases (15/44 = 34%) the intraperitoneal cystectomy was carried out without opening the cyst and the intact cyst was extracted using an endoscopic impermeable sack. We observed no cases of chemical peritonitis. The risk of recurrence after conservative treatment is 4% (two patients) and out of the ten patients for whom a second-look laparoscopy was performed only two (20%) presented adhesions. Laparoscopic treatment of dermoid ovarian cysts is feasible, safe, and effective. The treatment can be conservative in over 80% of the cases. The specific risk of chemical peritonitis can be countered by a change in the cystectomy technique. The use of an impermeable laparoscopic sack permits extraction of the cyst without any peritoneal contamination. PMID- 7992184 TI - Laparoscopic treatment of hydatid cysts of the liver. AB - We report for the first time treatment of hydatid cyst of the liver laparoscopically. The patient is a 27-year-old man who presented to our hospital with a 6-week history of recurrent right-upper-quadrant pain with abdominal ultrasound findings compatible with hydatid cyst of the liver. The cyst was approached laparoscopically using the same hydatid asepsis as in open surgery. The cyst was evacuated laparoscopically and marsupialized, and its remaining cavity was packed with omentum. The patient did well postoperatively and was discharged home on the third postoperative day. He had minimal biliary leak that ceased spontaneously on the fifth postoperative day. PMID- 7992185 TI - Laparoscopic resection of a nonparasitic liver cyst. AB - The spectrum of treatment options for symptomatic, benign, nonparasitic hepatic cysts has ranged from percutaneous aspiration to liver transplantation. Most large series have demonstrated that complete resection of the cyst is associated with the lowest rate of recurrence. However, a conventional open laparotomy may subject these patients to unacceptable morbidity given the benign nature of most of these lesions. We successfully performed a complete resection of a large hepatic cyst using a laparoscopic approach. Using an endoscopic GIA stapling device we were able to remove the cyst with minimal blood loss and in minimal operative time. The patient tolerated the procedure well, was discharged home on postoperative day 2, and in follow-up has been without recurrent symptoms. PMID- 7992186 TI - Laparoscopic repositioning of a continuous ambulatory peritoneal dialysis (CAPD) catheter. AB - We describe a laparoscopic technique for relieving obstruction of a continuous ambulatory peritoneal dialysis (CAPD) catheter. Laparoscopic repositioning of the catheter and omentectomy obviated the need for laparotomy in a patient with end stage renal disease. PMID- 7992187 TI - Right atrial to left atrial shunt through foramen ovale during pneumoperitoneum for laparoscopic cholecystectomy. AB - A 62-year old female patient in whom paradoxical right atrial to left atrial shunt flow through the foramen ovale was detected by transesophageal echocardiography during pneumoperitoneum for laparoscopic cholecystectomy was reported. This patient had a history of mitral valve replacement with residual tricuspid valve regurgitation. It was considered that the onset of paradoxical interatrial shunting through the foramen ovale might be caused not only by mechanical ventilation with positive end-expiratory pressure but also by pneumoperitoneum, especially in patients with heart disease, even if the intra abdominal pressure was maintained at 12 mmHg. PMID- 7992188 TI - Laparoscopic removal of dislocated ventriculoperitoneal shunts. Report of two cases. AB - In two patients the dislocated abdominal catheter of a ventriculoperitoneal (VP) shunt was successfully removed from the abdominal cavity by laparoscopy. Avoiding laparotomy, only two small abdominal incisions were necessary to insert the laparoscope and the grasping forceps. Postoperative course was uncomplicated except for protrusion of a part of the greater omentum through the umbilical incision in one patient. Both patients were mobilized on the operative day. Surgery required only 10 min, provided an excellent view of the entire abdomen, and led to prompt identification and removal of the lost catheter. PMID- 7992189 TI - The prone position. Using gravity for a clear view. AB - Obtaining a clear view during laparoscopic surgery in the posterior abdominal cavity, on the abdominal backwall, or during colon surgery is time consuming and therefore one of the major objections to these procedures. In an experimental setting we positioned the animals in the prone position using the abdominal flanks to introduce the trocars. Our experience with this position is that a clear and unobstructed view of the abdominal back wall and the large intestines is obtained, facilitating laparoscopic procedures in these areas. PMID- 7992190 TI - Laparoscopic oncologic proctosigmoidectomy with low colorectal anastomosis in a cadaver model. AB - The purpose of this study was to demonstrate that a standardized approach to laparoscopic proctosigmoidectomy in a cadaver model with (1) initial proximal ligation of the inferior mesenteric (IM) vascular pedicle, (2) complete mobilization of the splenic flexure, and (3) intraperitoneal stapled colorectal anastomosis can be accomplished in complete accordance with oncologic surgical principles. Using nine cadavers in the fresh state, six abdominal wall cannulas were placed so as to allow good access to the left colon and rectum. After identifying the left ureter and gonadal vessel, the IM pedicle was divided close to the aorta and the left mesocolon was separated from the retroperitoneal structures. The sigmoid colon was transected at the proximal resection line with an endoscopic stapler; then the splenic flexure and descending colon were completely mobilized. The rectum was freed circumferentially, dissected first posteriorly, laterally, and anteriorly, and then transected in its middle portion with an endoscopic stapler. The specimen was removed through a widened left-lower quadrant trocar incision and the anvil of a circular endoscopic stapler was placed into the proximal colon extraperitoneally. An intraperitoneal laparoscopic colorectal anastomosis was performed using a double-stapled technique. The median length of specimen was 53 cm (range 45-80 cm) and the median number of removed lymph nodes was 15 (range 11-20). A careful abdominal autopsy was carried out in all cadavers. Length of remaining inferior mesenteric artery was smaller than 1.5 cm in all cases and only one remaining lymph node (3 mm in diameter) was found adjacent to the IMA in one subject. No damage to either ureter occurred.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7992192 TI - Hypodermic needle illuminator. PMID- 7992191 TI - Intracorporeal instrumental ligation with reliable security. PMID- 7992193 TI - Patient position for laparoscopic surgery. PMID- 7992194 TI - AESOP robotic arm. PMID- 7992195 TI - Solitary inflammatory polyp harboring peridiverticular abscess. PMID- 7992196 TI - Framework for post-residency surgical education and training. The Society of American Gastrointestinal Endoscopic Surgeons. PMID- 7992197 TI - Pharmacologically induced cessation of burst activity in nigral dopamine neurons: significance for the terminal dopamine efflux. AB - Results obtained previously indicate that the firing pattern of midbrain dopamine (DA) neurons is of importance for the terminal DA release. In the present combined electrophysiological and microdialysis study, the influence of the firing pattern on striatal DA release was studied by using the previously observed ability of low doses of gamma-hydroxybutyrate (GHBA) to profoundly regularize the firing pattern of rat DA neurons in the substantia nigra (SN). Administration of GHBA (200 mg/kg, i.v.) did not significantly reduce the firing rate of any of the DA neurons recorded from, but rather caused a slight transient excitation. However, this dose of the drug caused a profound regularization of the firing pattern and abolished burst activity of the DA neurons. The DA concentration in the dialysate obtained from the striatum (10 min sampling periods) decreased with the lowest value (67% of predrug value) observed at the sampling period 20-30 min after the GHBA administration. As a complement to microdialysis, the 3-methoxytyramine (3-MT) accumulation in striatal tissue following monoamine oxidase inhibition was determined as an indirect measure of DA release in vivo. The 3-MT concentrations in the striatum decreased to 84% of controls following 200 mg/kg of GHBA. To exclude an effect on DA release conceivably mediated by GHBA locally in the striatum, GHBA (10(-7)-10(-3) M) was given locally in the dialysis probe and was found to increase DA in the dialysate (maximally to 140% of controls).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7992198 TI - Dopamine neuron membrane physiology: characterization of the transient outward current (IA) and demonstration of a common signal transduction pathway for IA and IK. AB - Dopamine neurons derived from the mesencephalon of embryonic rats were maintained in primary culture, identified and studied with whole-cell patch recording techniques. These neurons demonstrated a rapidly activating and inactivating voltage-dependent outward current which required the presence of K+ ions. This current was termed IA because of its transient nature. It was elicited by step depolarizations from holding potentials more negative than -50 mV and exhibited steady-state inactivation at a membrane potential more positive than -40 mV and half-maximal inactivation observed at -65 mV. This current rapidly achieved peak activation in less than 8 msec and decayed with a time constant (tau) of 58 +/- 5 msec. This current was observed in the presence of tetraethylammonium but was readily blocked by 4-aminopyridine (2-4 mM). This current was also observed to be modulated by stimulation of D2 dopamine receptors (DA autoreceptors) located on the dopamine neurons. Thus, both DA and the D2 receptor agonist quinpirole enhanced the peak IA observed, while the partial D1 receptor agonist SKF 38393 was without effect. The enhancement of IA was confirmed to be due to the activation of D2 receptors as the effects of either DA or quinpirole were blocked by the D2 receptor antagonists eticlopride and sulpiride, but not by the D1 receptor antagonist SCH 23390. Since we have previously demonstrated that the IK present in these cells is also enhanced by D2 receptor stimulation, we investigated the signal transduction pathways involved in coupling DA autoreceptors to both IA and IK. The response of both these potassium currents to DA autoreceptor stimulation was completely abolished by the preincubation of cultures with pertussis toxin, indicating the possible involvement of the G proteins Gi and G(o). In an attempt to further characterize which G protein may be involved, additional experiments were performed. The ability of DA autoreceptor stimulation to augment both currents was also blocked completely when G protein activation was prevented by the intracellular application of GDP beta S (100 microM). In contrast, irreversible activation of G proteins by intracellular application of the nonhydrolyzable GTP analog GTP gamma S (100 microM) mimicked the effects of DA autoreceptor stimulation on both IA and IK. In addition, the intracellular application of a polyclonal antibody that was selective for the alpha-subunit of G(o) completely abolished the DA autoreceptor modulation of both currents while preimmune serum was without effect.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 7992199 TI - Effects of haloperidol, quinelorane, and lithium on regional neurotensin/neuromedin N concentrations: further evidence for neurotensin/neuromedin N-dopamine interactions. AB - In order to further characterize the pharmacologic mechanisms that mediate the antipsychotic drug-induced increase in neurotensin (NT) in nucleus accumbens and striatum, the effects of three weeks treatment with psychotherapeutic levels of lithium alone or in conjunction with haloperidol were compared to the ability of haloperidol alone to alter NT and neuromedin N (NMN) regional brain concentrations in rats. A separate experiment examined the ability of a selective dopamine D2 receptor agonist, quinelorane, to alter NT/NMN regional concentrations after three weeks of treatment as compared to haloperidol, a D2 receptor antagonist. Haloperidol (1 mg/kg) increased both NT and NMN concentrations in several brain regions and these parallel peptide increases were highly correlated. Lithium chloride (0.4 mM) had no effect, either alone or with haloperidol, on NT/NMN concentrations. Quinelorane (1 mg/kg), however, effectively increased both NT and NMN concentrations in the caudate nucleus and nucleus accumbens, as did haloperidol (2 mg/kg). These data indicate that the induction of NT and NMN, whose adjacent sequences are contained in a pro-hormone product of a single gene, occurs in tandem and remains proportional, as well as demonstrating that putative D2 receptor agonists can produce effects on NT/NMN systems that are similar to D2 receptor antagonists. PMID- 7992200 TI - Local communication within dendritic spines: models of second messenger diffusion in granule cell spines of the mammalian olfactory bulb. AB - Dendritic spines are generally believed to play a role in modulating synaptically induced electrical events. In addition, they may also confine second messengers and thus topologically limit the distance over which second messenger cascades may be functionally significant. In order to address this possibility, computer simulations of transient second messenger concentration changes were performed. The results show the importance of spine morphology and binding and extrusion mechanisms in controlling second messenger transients. In the presence of intrinsic cytoplasmic binding sites and kinetic rates similar to that expected for calcium, second messengers were confined to the spine head. In the absence of binding/extrusion mechanisms, the size and time course of the input transient to the spine head influenced the second messenger transients that might be seen at the base of the spine neck and in other spines. Large and/or sustained increases in second messenger concentration in the spine head were communicated to the spine base and to other spine heads. The results emphasize the importance of a knowledge of breakdown pathways, concentrations and kinetics of binding sites, and extrusion mechanisms for understanding the dynamics of local chemical changes for dendritic spine function. PMID- 7992201 TI - Calcium signalling in bovine adrenal chromaffin cells: additive effects of histamine and nicotine. AB - In a previous report, we described the ability of two secretogogues, histamine and nicotine, to stimulate additive effects on catecholamine (CA) release and synapsin II phosphorylation in bovine adrenal chromaffin cells (BACC) [Firestone and Browning (1992), J. Neurochem., 58:441-447]. We hypothesized that these results were due to the combined effects on cytosolic Ca++ of the two distinct signalling pathways. We therefore examined the intracellular Ca++ signals stimulated by histamine and nicotine, alone and together. In Ca(++)-deficient medium, nicotine-stimulated signals were abolished, whereas histamine-stimulated signals were maintained, demonstrating that nicotine depended entirely on Ca++ influx for its effects. Indeed, the nicotine-stimulated signal could also be prevented using a Ca++ channel blocker, nicardipine. Further, the observation that exposure of BACC to thapsigargin reduced histamine-stimulated Ca++ signals verified that histamine mobilizes Ca++ from intracellular stores. Thus, the two secretogogues mobilize Ca++ from distinct pools. When BACC were stimulated with the two secretogogues together, the resulting Ca++ signal was greater than that from either alone. These data are consistent with a model in which two distinct sources of Ca++ can summate within the cell, producing a greater Ca++ signal and, hence, a greater effect on neurotransmitter release. PMID- 7992202 TI - Perinatal cocaine exposure decreases the number of spontaneously active midbrain dopamine neurons in neonatal rats. PMID- 7992203 TI - Quinazolinone cholecystokinin (CCK)-B antagonists decrease midbrain dopamine unit activity. PMID- 7992204 TI - [The prevalence of cardiovascular diseases among the workers and employees of organized collectives based on cardiological screening data]. AB - Altogether 90.2 thousand workers of 33 enterprises of the cities and villages were examined. Of these, men (mean age 41.1 +/- 1.1 years) accounted for 39.2%. Use was made of an automated system for mass cardiological screening and dispensary observation made over time of the workers and employees of the organized bodies by computer EC, CM and IBM PC XT/AT. Different cardiological diseases were revealed in 38.4% of the examined. Out of the total number of the patients, 44.5% were diagnosed to have arterial hypertension (AH) whereas 18.6% coronary heart disease (CHD). CHD was widely prevalent in the working middle-aged and elderly men and women. Angina pectoris of effort appeared to be most frequently occurring form of CHD, accounting for 70.4% of the total number of CHD patients. Myocardial infarction was discovered in 0.9% of men and 0.3% of women. AH was identified in 40.8% of CHD patients, whereas 38% demonstrated borderline AH. Therefore, associated CHD and elevated blood pressure was recorded in 78.8% of the patients. A relationship was established between the prevalence and incidence of cardiovascular diseases and sex and age. PMID- 7992205 TI - [Silent myocardial ischemia in patients with ischemic heart disease in assessing the severity of the disease]. AB - Ninety patients with angiographically confirmed diagnosis of coronary heart disease were examined. The ECG exercise test and Holter ECG monitoring were carried out. Silent ischemia (SI) was revealed in 40 patients (44.4%). According to the data of examinations, the patients with SI episodes were clinically graver than those without SI. In the SI group, 60% of the patients had prognostic criteria of a clinically high coronarographic risk, namely stenosis of the trunk of the left coronary artery, dangerous localisation of one or more arteries in "incomplete" myocardial infarction, and significant sclerosis of three main coronary arteries. Practically all the patients were at high risk for SI episodes. The probability of a high risk increases if SI is associated with such factors as the total ischemic burden of more than 30 minutes and ST depression magnitude equal to 1.5 mm in the ECG exercise test or 3 mm in Holter ECG monitoring. PMID- 7992206 TI - [The antioxidant ceruloplasmin: its effect on lipid peroxidation, blood rheology and the course of stenocardia]. AB - Lipid peroxidation, antioxidant system and hemorheology were studied in the course of ceruloplasmin treatment given to 47 patients with ischemic heart disease (IHD). Coupled changes in the above systems seem to be involved in pathogenesis of IHD variants. Ceruloplasmin effectively inhibits lipid peroxidation, corrects hemorheological disorders, improves IHD running. PMID- 7992208 TI - [The role of systolic and diastolic disorders in the development of heart failure]. PMID- 7992207 TI - [Hypoxic training in prevention and treatment]. PMID- 7992209 TI - [Experience with the use of computer processing of the cardiac signal in the bedside ECG monitoring of patients in a cardiological resuscitation department]. PMID- 7992210 TI - [The characteristics of the lipid-hormonal interrelations in young men with a history of myocardial infarct (based on family registry data in Novosibirsk and Bishkek)]. AB - Altogether 226 male probands who suffered large-focal or transmural myocardial infarction (MI) before reaching 50 years were examined in Novosibirsk and Bishkek in one stage according to the unified program. In Novosibirsk all the probands were Russians whereas in Bishkek 75 probands were Kirghizs and 71 were Russians. The probands were examined within a period of 1 to 3 years after MI. The lipid and lipoprotein plasma content was determined by standardized methods on a Tekhnikon AAP autoanalyzer. The content of thyroid hormones, insulin and cortisol was measured by means of RIA-kits and that of apolipoprotein B (ApoB) by radial immunodiffusion. It turned out that the patients from Novosibirsk demonstrated the highest content of cholesterol, low density lipoprotein cholesterol, the highest index of atherogenicity, the highest concentration of ApoB, and hyperinsulinemia. In the probands of both nationalities from Bishkek, the lipid spectrum did not differ substantially from the populational norm, the content of ApoB in the Russian probands was slightly lower than in those from Novosibirsk whereas in Kirghizs, the least content of thyroxin was recorded. PMID- 7992211 TI - [The effect of thrombolytic therapy with the preparation APSAC on the course of myocardial infarct]. AB - To evaluate the influence of thrombolytic therapy (TT) on the course of acute myocardial infarction (AMI), a comparative analysis of clinical and pathological findings was conducted. The latter included post mortem examination of 35 myocardial samples from patients treated with APSAC in the acute phase of the infarction. The analysis indicated the predominance of cases with unfavourable coronary heart disease, severe myocardial damage and severe AMI complications in the group of the decreased patients. The following beneficial effects of TT were reported: relatively safe stromal and parenchymal myocardial components, earlier regeneration of the connective tissue. Late TT had a negative effect on MI because more hemorrhagic infarctions occurred. The combination of TT and myocardial repair modulators is proposed. PMID- 7992212 TI - [The regression of the structural-functional changes in the hypertrophic left ventricle during the long-term correction of the arterial pressure with Inhibace (cilazapril)]. AB - The regression of structural and functional alterations in the hypertrophic left ventricle was measured in the course of long-term correction of arterial pressure with a new inhibitor of angiotensin-converting enzyme ingibeis (chilasapril) in 23 patients with essential hypertension stage II-III. The results were for the most part obtained at echocardiography providing basic hemodynamic parameters and those of left ventricular diastolic function. Adaptability of the hypertrophic myocardium in response to physical loading was studied dynamically under isometric exercise test. The findings proved high efficacy of chilasapril in monotherapy of arterial hypertension. Long-term (6 months) therapy of left ventricular hypertrophy provides regression of the latter and improves left ventricular diastolic function, pumping capacity. In the course of arterial hypertension correction relevant patients with associated coronary heart disease improved their condition, demonstrated less frequent ECG changes indicative of ischemia. PMID- 7992213 TI - [The use of graded walking with hypertension patients]. AB - Different walking regimens adjusted in duration and intensity to the circulation functional class were prescribed to patients with essential hypertension (EH) stage I and II. Functional class of the circulation was determined at bicycle exercise, the motor regimen was under the control of ECG Holter monitoring. Regular walking improved the patients' health, lowered blood pressure, enhanced physical performance. The authors advocate graded walking as one of nonpharmacological forms of outpatient EH therapy. PMID- 7992214 TI - [The possibilities of preventing hypertension and the characteristics of the psychological set for its management in rural inhabitants]. AB - At examination of 360 hypertensive subjects living in rural areas it was found that the examinees were quite indifferent to their health. This is explained by poor knowledge of hypertension and its complications, inadequacy of the patients psychophysical condition, lack of medical prevention activity. A questionnaire survey of the physicians-in-charge revealed that 24% of them were unaware of the risk factors, 68% did not care for relevant correction, though they had diagnosed the risk factors in themselves. In self-rating the physicians were not confident, showed indifference to own health and future. The authors believe that the condition of the patients was in many respects due to social and psychological dysadaptation of their physicians who had lost their interest in preventive medicine. PMID- 7992215 TI - [The effect of Lomir (isradipine) on the tolerance for physical loading and on the gas exchange indices of patients with primary pulmonary hypertension]. AB - Spirometry and bicycle ergometry were performed before and 3 weeks, 6 months after lomir treatment (mean dose 10.62 +/- 2.59 mg/day) of 8 patients with primary pulmonary hypertension. It was found that 3 weeks of the treatment produced a significant increase in the maximum power working capacity and performance, in 6 months of the treatment there were positive trends in gas exchange: anaerobic threshold became higher and maximum oxygen consumption rose. Thus, lomir is recommended for management of primary pulmonary hypertension as it improves exercise tolerance and gas exchange measured by means of spirometry and bicycle ergometry useful both for evaluating functional condition of the patients and the disease advance as well as its response to the therapy conducted. PMID- 7992216 TI - [Permanent repetitive nonparoxysmal ventricular tachycardia. I. The electrocardiographic manifestations and possible mechanisms of its occurrence]. AB - A total of 20 patients (16 males and 4 females) with repetitive nonparoxysmal ventricular tachycardia (RNVT) underwent Holter monitoring of ECG, bicycle exercise test, intracardiac electrophysiological measurements. The findings evidence for a principal difference of this tachycardia form from paroxysmal ventricular tachycardia by trigger mechanism. All the tests performed showed rhythm-dependence of RNVT, tachycardia cannot be initiated by electrocardiostimulation, but can be stopped after intravenous introduction of finoptin. It is evident that this form of cardiac arrhythmia is due to the mechanism of pathological ectopic automatism represented, most likely, by trigger activity, but not re-entry, as it is in the majority of patients with paroxysmal ventricular tachycardia. PMID- 7992217 TI - [Permanent repetitive nonparoxysmal ventricular tachycardia. II. The results of using anti-arrhythmia preparations and the characteristics of its long-term course]. AB - A total of 20 patients with repetitive nonparoxysmal ventricular tachycardia (RNVT) underwent Holter ECG monitoring to test efficacy of successive oral antiarrhythmic drugs. The response was recorded in 50% of the patients. Although the effect of the drugs persisted for a few months only, RNVT ran without severe symptoms, in contrast to paroxysmal ventricular tachycardia. Long-term course of RNVT is characterized by dilatation of the left ventricular compartment under increasing ejection fraction and absence of cardiac insufficiency. A close relationship exists between the end-diastolic volume, ejection fraction of the left ventricle and RNVT duration. This is attributed to heart adaptation to long term activity in the conditions of tachycardia. PMID- 7992218 TI - [The neuroregulatory modulation of the hemodynamic reactions to physical loading in patients with cardiac arrhythmias]. AB - Course activations of artificial stable functional links (ASFL-II) simulating tranquilizer hidazepam were given to 36 arrhythmic patients with effort syndrome (ES) and coronary heart disease. Hemodynamic responses to ASFL-II at bicycle exercise were evaluated. It was found that ASFL diminish pressor vascular reactions and increase hemodynamic resources at bicycle exercise, especially of ES patients. The modulating activity of ASFL-II in relation to hemocirculation is attributed to alterations in the central neuromediator mechanisms. PMID- 7992220 TI - [Plasmapheresis and immunosorption in cardiology]. PMID- 7992221 TI - [Plasmapheresis in the combined therapy of neurological diseases]. PMID- 7992219 TI - [Serum neopterin, bacteremia and viral antibodies in dilated cardiomyopathy]. AB - Quantitation of neopterin and morphological examination of bacteria circulating in the blood of 28 patients with dilated cardiomyopathy gave evidence for elevated neopterin concentrations in 22 of the examinees (> 10 nM/l). The highest neopterin levels occurred in patients with L-form bacteria. Concentrations of neopterin and antibodies to cytomegalovirus, herpes simplex were related. The above antibodies were associated with high neopterin levels in the serum. It is suggested that high amounts of serum neopterin may result from combination of viral and bacterial infection in dilated cardiomyopathy sufferers. PMID- 7992223 TI - [The basic antihypertensive drugs for the long-term secondary prevention of cardiovascular diseases (the working group of the multicenter study Captopril and the Quality of Life)]. PMID- 7992222 TI - [The complications of plasmapheresis and the possible means for their prevention in glomerulonephritis patients]. PMID- 7992224 TI - [Emergency states in cardiology]. PMID- 7992225 TI - [Molsidomine (Corvaton)]. PMID- 7992226 TI - [The kallikrein-kinin system: its significance in circulatory failure and the effect of angiotensin I-converting enzyme inhibitors]. PMID- 7992227 TI - Progressive growth of rat bladder carcinomas after exposure to prolonged uracil induced urolithiasis. AB - Dietary uracil at the 3% level induces urinary bladder tumors in rats through urolithiasis-dependent mechanical irritation. In the present study, comparison of lesions induced by uracil administration over the different periods of 36 weeks (middle-term) and up to 103 weeks (long-term) revealed significant elevation of both incidences and multiplicity of transitional cell carcinomas (TCCs) in the long-term group. Histopathological assessment in terms of tumor biology further demonstrated significantly higher grading on the basis of the degree of cellular and structural atypia, and greater depth of invasion in the long-term group. Application of markers for cell proliferation activities including proliferating cell nuclear antigen (PCNA) and silver-binding nucleolar organizer regions (AgNORs) also revealed significantly elevated AgNOR counts in the long-term group TCC. AgNOR counts and PCNA rates in TCCs showed relation to the histological grades. Thus the present study demonstrated that prolonged uracil-induced urolithiasis causes more biologically aggressive bladder carcinomas with invasive potential. Continuous stimulation of cell proliferation presumably has the potential to facilitate multiple genetic alterations leading to development of more malignant carcinomas. However, it should be borne in mind that the difference in bladder cancer development might also be related to the fact that the animals survived longer and that the early lesions therefore had more time to progress to more advanced stages. PMID- 7992228 TI - Lack of promoting effect of proline on bile duct cancer development in dimethylnitrosamine-initiated hamster livers. AB - Bile duct hyperplasia caused by proline is believed to represent a chemical effect of the liver fluke, Fasciola hepatica, and the resultant cell division might be expected to play a role as a tumor promoter. To investigate the potential promoting effect of proline on bile duct cancer development, Syrian hamsters were therefore divided into 8 treatment groups: dimethylnitrosamine (DMN) + proline intraperitoneally (i.p.); DMN + proline s.c.; DMN + saline i.p.; DMN + saline s.c.; proline i.p.; proline s.c.; saline i.p.; and saline s.c. DMN was injected i.p. at 20 mg/kg to the animals 2 weeks prior to commencement of proline treatment, whereby 1 ml of a 2 M solution was given by i.p. or s.c. injection 3 times a week for 20 weeks. At the end of week 42, assessment of preneoplastic lesion development did not reveal any significant modulating influence of proline on DMN-initiated lesion development nor did it itself cause persistent bile duct hyperplasia. PMID- 7992229 TI - Impact of higher doses of vitamin C in modulating pesticide genotoxicity. AB - The modulatory effect of higher doses of vitamin C (ascorbic acid) on the genotoxicity of the three pesticides (endosulfan, phosphamidon, and mancozeb) was assessed in the in vivo micronucleus test in Swiss albino mice. Concurrent administration of the vitamin in a dose (20 mg/kg bwt/day) equivalent to double the human therapeutic one, along with each of the three pesticides, was most effective as an antimutagen. The therapeutic dose (10 mg/kg bwt/day) was comparatively less so, and the quadruple (40 mg/kg bwt/day) of it did not show any further amelioration. PMID- 7992230 TI - Comparison of DNA adduct levels in human placenta from polychlorinated biphenyl exposed women and smokers in which CYP 1A1 levels are similarly elevated. AB - Previous studies demonstrated that cigarette smoking is associated with high elevations in levels of both cytochrome P450 1A1 (CYP1A1) and DNA adducts in human placenta. To date, the identity of the smoking related DNA adducts is not known. The DNA adducts identified in placenta of smokers could result from chemicals present in cigarette smoke, substances formed by CYP 1A1 metabolic activation of endogenous compounds, noncigarette related exposures or a combination of these processes. Exposure to contaminated rice oil containing large doses of polychlorinated biphenyls (PCBs) and polychlorinated dibenzofurans (PCDFs) also resulted in massive elevation of CYP 1A1 in human placenta but formation of DNA adducts directly from this exposure has not previously been reported. The purpose for comparing the two populations was to test the hypothesis that if CYP 1A1 induction results in the metabolic activation of endogenous compounds, then DNA adducts should also be present in PCB/PCDF exposed tissues exhibiting high CYP 1A1 activity and some of the adducts detected in the placental DNA from smokers may be identified as those derived from the metabolic activation of endogenous compounds. To test this hypothesis, we measured DNA adducts using 32P-postlabeling to analyze placental DNA from women exposed to PCB/PCDF and from cigarette smokers where levels of CYP 1A1 were similarly elevated. There was no evidence of DNA adducts among specimens obtained from PCB/PCDF exposed individuals. These data suggest that CYP 1A1 induction alone (in the absence of cigarette smoking) does not induce the formation of DNA adducts detectable by this approach, and that smoking related adducts are not a consequence of CYP 1A1 induction mediated activation of endogenous compounds or xenobiotics other than cigarette smoke. PMID- 7992231 TI - Effect of phenacetin pretreatment on renal pelvic carcinogenesis by N-butyl-N-(4 hydroxybutyl)nitrosamine in NON/Shi mice of both sexes. AB - Influences of phenacetin (PH) pretreatment on renal pelvic carcinogenesis induced by N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN) were examined in NON/Shi mice of both sexes. Histopathological examination revealed that PH pretreatment enhanced not only the induction of urinary tract carcinoma but also distant metastasis of renal pelvic carcinoma by BBN in male mice. The high incidence of urinary tract carcinoma by PH pretreatment might be due to hydronephrosis and epithelial proliferative lesions enhanced by PH, since a single treatment of PH induced hydronephrosis in all mice and simple hyperplasia in 70-80% of mice used. PMID- 7992232 TI - How to avoid calculations during treatment of numerous groups of laboratory animals with a single appropriate dose in mg/Kg b.w.: an original technical note. PMID- 7992233 TI - Coagulation, fibrinolysis and haemorheology in premenopausal obese women with different body fat distribution. AB - Recently waist/hip ratio (WHR), a marker of body fat distribution, has been described as a risk factor for cardiovascular disease (CVD). The aim of the present study was to evaluate the influence of body fat distribution on metabolic, haemostatic and haemorheological pattern in premenopausal obese women with different WHR. Fourty premenopausal obese women were subdivided into two groups, matched for age and body mass index (BMI): 20 women with abdominal obesity (WHR = 0.94 +/- 0.02) and 20 women with peripheral obesity (WHR = 0.77 +/ 0.03). Twenty nonobese women were recruited as control group. The abdominal obesity group had significantly higher blood glucose, triglycerides, total cholesterol, Apolipoprotein B and plasma insulin levels and lower high density lipoprotein (HDL) cholesterol and Apolipoprotein A1 levels than the control group. All the haemostatic (figrinogen, Factor VII, plasminogen activator inhibitor (PAI) activity and tissue plasminogen activator (t-PA) antigen (Ag) pre venous occlusion (VO)) and haemorheological parameters (haematocrit, whole blood filterability, blood and plasma viscosity) were significantly higher in the abdominal obesity group as compared to the control group. In contrast, mean values of t-PA (Ag) post VO were significantly lower in abdominal obese women. Moreover positive correlations between WHR and plasma insulin (r = 0.68, p < 0.05), between WHR and fibrinogen (r = 0.63, p < 0.05) and between WHR and PAI pre VO (r = 0.71, p < 0.05) and a negative correlation between WHR and t-PA (Ag) post VO (r = -0.55, p < 0.05) were found.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7992234 TI - ADP-, PAF- and adrenaline-induced platelet aggregation and thromboxane formation are not affected by a thromboxane receptor antagonist at physiological external Ca++ concentrations. AB - Thromboxane (TX) receptor antagonists are of considerable clinical interest in prevention of acute thrombembolic vessel occlusion. This study demonstrates that the selective TX receptor antagonist, daltroban, at a concentration (10 microM) that does not inhibit TX synthesis, markedly inhibits ADP-, PAF- and adrenaline induced platelet secretion and TX formation. With the exception of ADP-induced platelet secretion, these actions are only detectable in citrated platelet-rich plasma but not in plasma anticoagulated by hirudin. Since TX antagonists are supposed to act at physiological external Ca++ concentrations in the clinics, it is questionable whether in vitro studies in Ca(++)-deprived media are the optimum model to evaluate the clinical potential of these compounds. PMID- 7992235 TI - A garlic derivative, ajoene, inhibits platelet deposition on severely damaged vessel wall in an in vivo porcine experimental model. AB - Ajoene, (E,Z)-4,5,9-trithiadodeca-1,6,11-triene 9-oxide, is a potent antiplatelet compound isolated from alcoholic extracts of garlic. In vitro, ajoene reversibly inhibits platelet aggregation as well as the release reaction induced by all known agonists. We used a well characterized perfusion chamber to study the in vivo effects of ajoene on platelet deposition onto a highly thrombogenic, severely damaged arterial wall, obtained by stripping off the intimal layer and exposing tunica media. Platelet-vessel wall interaction and the effect of ajoene was studied under flow conditions of high and low local shear rate that mimics laminar blood flow in small and medium size arteries (1690 sec-1 and 212 sec-1). Our results indicate that administration of ajoene to heparinized animals, significantly prevents thrombus formation at local low blood shear rate. Ajoene does not inhibit binding of vWF to GPIb, therefore, it does not affect platelet adhesion. In fact, although ajoene impairs fibrinogen and vWF (less efficient) binding to GPlIb/IIIa, it does not totally inhibits platelet deposition to the substrates at any of the shear rates used in this study. Our present results, under in vivo flow conditions and in the presence of physiological calcium levels, suggest that ajoene may be potentially useful for the acute prevention of thrombus formation induced by severe vascular damage, mainly in arterial sites with local low shear rates. PMID- 7992237 TI - The low pH stability of human coagulation factor XII (Hageman factor) is due to reversible conformational transitions. AB - Factor XII undergoes autoactivation when bound to negatively charged surfaces. To gain insight into the mechanism of factor XII autoactivation and stability at low pH, structural studies in the presence and absence of a soluble surface, dextran sulfate, at pH 5.3 and pH 8.3 were carried out. The circular dichroism data indicate that the secondary structure at pH 5.3 is only modestly different from that at pH 8.3. However, large changes in the secondary structure are found to occur when factor XII is exposed to pH 5.3 in the presence of surface. Changes in tertiary structure at low pH are also evident from the difference in tryptophan fluorescence and chemical reactivity of the histidine residues. Factor XII binds to the surface even at pH 5.3 though it is inactive at this pH. It is concluded that factor XII adopts a different conformation at pH 5.3 and causes it to interact differently with dextran sulfate. This results in an obstructed cleavage site that accounts for its stability at low pH. PMID- 7992236 TI - Platelet aggregability in relation to the anaerobic threshold. AB - Platelet aggregability might be increased during physical exercise. This, in turn, has been explained by the elevation of plasma catecholamines and by the state of lactic acidosis, which occur at high exercise intensities. The purpose of this investigation was to study the relationship between changes in platelet aggregability and exercise intensity, the latter being determined in reference to the anaerobic threshold (AT). Each of sixteen male subjects performed an incremental exercise test in order to determine both (a) his running velocity (VAT) corresponding to his anaerobic threshold and (b) his running velocity (V4mM) corresponding to 95% of his running velocity eliciting a blood lactate concentration of 4 mM.l-1. Three and six days after this preliminary test, respectively, each subject performed an exercise test of 30 minutes, at a constant running velocity of either VAT or V4mM. Running velocity for each day's test was randomly assigned. Both capillary and venous blood samples were collected immediately before and immediately after each test, and after 30 minutes of recovery from each test, respectively. Capillary blood samples were obtained for determination of blood lactate concentration, whereas venous blood samples were obtained for determination of platelet count, and platelet aggregation in response to ADP and collagen, respectively. Platelet count significantly increased (p < 0.001) immediately after the 30-minute-tests at either VAT and V4mM, remaining elevated (p < 0.05) after 30 minutes of recovery from the tests at V4mM. The results did not evidence any significant increase in platelet aggregability with exercise, except for aggregation response to ADP immediately after the tests performed at V4mM (p < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7992239 TI - Bleeding times related to serum triglyceride levels in healthy young adults. AB - A diet rich in fish tends to increase the bleeding time both in patients and healthy controls. Another effect of such a diet is a reduction in serum triglyceride levels in the individuals. It is not known whether these two effects are interrelated. In order to rule out effects of selenium in the fish diet, half of a control group consumed bread enriched with selenium while the other half had a normal diet. This combined control group (n = 21) was compared with healthy volunteers (n = 11) eating 250 g of fish daily for six weeks. Blood tests were performed at the start of the study, after three weeks and at the end. Changes in bleeding time were then related to changes in hemostatic variables and serum lipids. An inverse correlation (r = -0.41, p = 0.001) was present in the controls between serum triglyceride levels and bleeding times, but neither of the two variables changed in the course of the study. A negative correlation was observed in the fish eating group, and a change in the variables mentioned occurred in an orderly manner in the course of the study: a prolongation of the bleeding time from the start of the study to the end was only seen in individuals with low triglyceride levels, i.e. less than 1 mmol/L. Selenium in the diet, on the other hand, did not affect any of the observed variables.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7992238 TI - Inhibition of human platelet aggregation by GR91669, a prototype fibrinogen receptor antagonist. AB - In order to produce more potent and specific fibrinogen receptor (GpIIb/IIIa) antagonists, the Arg-Gly of a chemical series based upon Arg-Gly-Asp was replaced by alkyl chains of varying lengths. The most potent in this series, GR91669, inhibited aggregation of human gel-filtered platelets (GFP) in vitro induced by ADP or the thromboxane A2 mimetic, U46619, with IC50 values of 200nM and 500nM respectively and was selected for further studies. Its inhibitory effects on GFP were reversed by addition of excess fibrinogen. The compound also inhibited ADP- or U46619-induced platelet aggregation in human whole blood (IC50 values of 700nM in both cases). 125I-Fibrinogen binding to ADP-stimulated platelets was inhibited by GR91669 with an IC50 (65nM) similar to that against platelet aggregation. GR91669 (1mM) did not inhibit U46619-induced platelet shape change or 14C-5HT secretion from platelets stimulated by collagen, U46619 or thrombin. Therefore GR91669 inhibits aggregation but has no significant effect on stimulus-response events, a profile consistent with fibrinogen receptor blockade. In addition, GR91669 (1mM), unlike echistatin or Gly-Arg-Gly-Asp-Ser, did not disrupt vitronectin recptor-dependent attachment of cultured HUVECS in vitro and similarly did not inhibit Mac-1 dependent adhesion of human granulocytes. Thus, of the integrins tested, GR91669 appears to be specific for GpIIb/IIIa. Following intravenous administration to marmosets of 1 or 10 mg/kg GR91669, ADP (10 microM) induced platelet aggregation ex vivo was abolished for 15 and 60 minutes respectively. Greater than 50% inhibition was maintained for 30 minutes and 2 hours respectively. GR91669, therefore appears to be a potent, specific fibrinogen receptor antagonist in vitro and which is also active in vivo. PMID- 7992240 TI - Amino acid substitutions of the P2 residue of human antithrombin that either enhance or impair function. AB - Recombinant forms of human antithrombin (AT) were expressed in COS-1 cells, and their interaction with human thrombin characterized by comparing the reactivity of two engineered mutant forms of AT with the wild-type recombinant. Both mutant forms contained single amino acid substitutions of Asp (G392D) or Pro (G392P) for the wild-type Gly, at residue 392, termed the P2 position with reference to the adjacent reactive centre bond. All three forms of AT co-migrated on Western blots, with an apparent molecular weight of 58 kD, with endoglycosidase F treatment reducing their mobility to 47 kD. The two mutant forms of AT reacted with thrombin differently from the wild-type molecule, in that the G392D substitution abrogated the thrombin inhibitory capacity of the protein, while the G392P substitution enhanced the reactivity of the recombinant mutant AT with thrombin. Under pseudo-first order conditions, the second order rate constants for the reaction of the recombinant wild-type and G392P mutant AT were determined to be 1.4 x 10(4) L-mol-1 sec-1 and 3.0 x 10(4) L-mol-1 sec-1, respectively, a difference of 210%. In contrast, in the presence of heparin, the reaction rates of the G392P and wild-type AT forms with thrombin, differed by less than 25%. We conclude that the P2 position of AT is an important residue for AT to express its inhibitory activity, alterations to which can either enhance or impair the inhibition of thrombin by AT. PMID- 7992241 TI - Degradation of the alpha-chain of fibrin by human neutrophil elastase reduces the stimulating effect of fibrin on plasminogen activation. AB - The degradation of fibrin by human neutrophil elastase (HNE) and the interference of such degradation on the stimulating effect of fibrin on plasminogen activation by tissue plasminogen activator (t-PA) was studied. By using SDS electrophoresis and Western blotting with subsequent immunostaining with monoclonal antibodies, degradation of the fibrin molecule was monitored. This degradation was related to the stimulating effect on plasminogen activation. Degradation of the alpha-chain was seen to occur before degradation of the beta- and gamma-chains. On the alpha chain it was found that C-terminal degradation occurred prior to visible degradation of the N-terminal end. This C-terminal degradation was associated with a fall in the stimulation of plasminogen activation, coinciding with a corresponding reduction in the polymerization of fibrin. With further degradation, including N-terminal proteolysis of the alpha-chain, the stimulating effect of fibrin was reduced to that of fibrinogen. CONCLUSIONS: Our results indicate that HNE degradation of the alpha-chain of fibrin occurs initially from the C-terminal end, affecting the polymerization of fibrin. This impaired polymerization may be important for the observed reduction in the t-PA mediated plasminogen activation. PMID- 7992242 TI - Plasma fibronectin and estrogen replacement therapy. PMID- 7992243 TI - Fibrinogen structure, activation, polymerization and fibrin gel structure. PMID- 7992244 TI - Fibrin deposition and fibrin degradation products in atherosclerotic plaques. AB - Soluble fibrin/fibrinogen-related antigens and insoluble fibrin are present in virtually all samples of human aortic intima. Components of the soluble fraction were identified by SDS-PAGE and immunoblotting with specific antisera. The fibrinogen was characterized by increased proportions of low molecular mass (Mr) species (300 and 280 kD), the FDP by fragments DY and DD derived from crosslinked fibrin, and by fragment E that lacked fibrinopeptide A (FPA). Experiments suggest that fibrin is formed in situ, and free thrombin was present in all 10 samples analysed for prothrombin-related antigen (PtRA). Fibrin-derived fragment E is mitogenic, so fibrin degradation may provide continuing stimulation of smooth muscle cell (SMC) proliferation. PMID- 7992245 TI - Fibrinogen and fibrin in the arterial wall. PMID- 7992246 TI - Sites in fibrin involved in the acceleration of plasminogen activation by t-PA. Possible role of fibrin polymerisation. AB - Polymeric fibrin is a strong enhancer of the activation of plasminogen by t-PA. At least two types of sites are involved in this enhancement i.e. a site within A alpha-(148-160), and a site within gamma-(311-379). These sites are not accessible in fibrinogen, but are exposed upon conversion of fibrinogen to fibrin. This explains why fibrinogen has no rate-enhancing properties, and helps to explain the effects of fibrin. Fibrin with its ordered structure appears to exert its rate-enhancing effect by presenting the above sites for interaction with t-PA and plasminogen; thus concentrating and correctly orienting these two reactants on its surface and inducing conformational changes which lead to higher catalytic efficiencies. PMID- 7992247 TI - Fibrinogen, a vascular risk factor: a simple marker or a real cause of vascular lesion? PMID- 7992248 TI - Pharmacological approaches of fibrin gel architecture modulation and thrombus degradation: its implication in atherogenesis and thromboembolism disease. PMID- 7992249 TI - How does ticlopidine treatment lower plasma fibrinogen? AB - Many clinical studies have evaluated the clinical efficiency of ticlopidine in vascular pathology and in few of these studies the plasma Fg level was determined as a biological parameter and not a primary end point. All these studies are heterogeneous because plasma Fg concentration have been measured using various methods, patients were included at various time after the acute event and were followed over a period of 1 to 24 months of treatment with ticlopidine, patients suffered from various pathology: peripheral arterial disease, cerebrovascular disease, diabetes or polycythemia vera. Despite the heterogeneity of these prospective studies, a general trend indicates a decrease in the plasma Fg levels by 10 to 25% with ticlopidine compared to placebo. This decrease in circulating Fg was associated with clinical improvement, and, when studied, hemorheological modifications (decreases in whole blood and plasma viscosities). The mechanism of ticlopidine action is discussed. PMID- 7992250 TI - Evaluation of annexin V as a platelet-directed thrombus targeting agent. AB - Annexin V is a human phospholipid binding protein (M(r) 36,000) that binds with high affinity to activated platelets in vitro. We studied the biodistribution and thrombus binding of annexin V in rabbit and swine models of fully occlusive arterial thrombi formed 1-2 h prior to injection of annexin V. Iodinated annexin V was cleared from blood in a rapid early phase (t1/2 = 6.4 min, 76% of radioactivity) and a slower late phase (t1/2 = 71 min, 24% of radioactivity). Organ uptake was highest in the kidney and spleen and lowest in heart and skeletal muscle. Thrombus/blood uptake ratios were (mean +/- SEM): 6.39 +/- 1.80 for rabbit iliac artery, 6.97 +/- 1.45 for swine carotid artery, and 7.68 +/- 1.70 for swine femoral artery (all p values < 0.01 versus control artery); a control protein, ovalbumin, showed an uptake ratio of 0.59 +/- 0.08 in swine femoral artery thrombi. These results indicate that annexin V is useful as an agent for selective targeting of platelet-containing thrombi. PMID- 7992251 TI - Salivary PAF in acute myocardial infarction and angina: changes during hospital treatment and relationship to cardiac enzymes. AB - Salivary levels of platelet activating factor (PAF) were measured together with serum CPK and interleukin 2 receptor in 30 patients admitted to the coronary care unit, 9 patients with pulmonary tuberculosis, 10 with acute severe asthma and 8 normal controls. 16 of the 30 C.C.U. patients had sustained a acute myocardial infarction (M.I.) 5 had acute angina and the remaining 9 had non cardiac chest pain. Salivary PAF on admission was significantly higher in the M.I. Patients than in the normal subjects, asthmatics, tuberculosis patients and those with non cardiac chest pain (p < 0.001 in all cases) but not those with angina. After 48 hours PAF levels fell in the subjects with M.I. (p < 0.01) and no significant difference was seen between any group. PAF levels did not show any relationship with CPK levels or site of infarct in the M.I. patients. Interleukin 2 receptor was not significantly raised in the M.I. group as a whole but some individual patients showed markedly increased serum levels, but these levels did not correlate with either salivary PAF or serum CPK. PMID- 7992252 TI - High plasma levels of plasminogen activator inhibitor 1 (PAI-1) in polycythemia vera and essential thrombocythemia are associated with thrombosis. AB - We attempted to determine if a hypercoagulability state exists in patients with polycythemia vera (PV) and essential thrombocythemia (ET). We studied the hematocrit level, platelet count, use of any antiaggregant drugs, thrombotic or bleeding accidents and plasma levels of antithrombin III, protein C, total protein S, free protein S, vWF:Ag (Von Willebrand's factor related antigen), thrombin-antithrombin complexes, D-dimer, fibrinolytic activity, tissue plasminogen activator, plasminogen and PAI-1 in 33 patients (19 with ET and 14 with PV). PAI-1 plasma concentration was significantly higher in, both ET and PV patients than in the control group, and were higher in those patients with previous thrombotic episodes than in asymptomatic patients or with previous bleeding episodes. Increasing age was associated to more thrombotic episodes while younger patients presented with more hemorrhagic complications. A linear correlation between platelet count and PAI-1 levels in PV patients (r = 0.44, p < 0.05) and ET patients (r = 0.30, p < 0.05) was found. Fibrinolytic activity in patients with ET was significantly decreased when compared to the control group. A hypofibrinolytic state could be an additional factor which could be used as a predictive index of the thrombotic or bleeding tendency in each patient. PMID- 7992253 TI - Fibrin in human plasma: gel architectures governed by rate and nature of fibrinogen activation. AB - The porosity, fiber dimension and architecture of fibrin gels formed in recalcified plasma on addition of thrombin are, within a certain range of thrombin concentrations, determined by the initial rate of fibrinogen activation. Furthermore, the initial network formed in this range creates the scaffold into which subsequently activated fibrinogen molecules are deposited. Change in thrombin concentration that occurs during gelation, as a result of indigenous thrombin generation in plasma, does not qualitatively alter this scaffold. The formation of the networks obeys a more complex rule when low amounts of thrombin are added or with recalcified plasma without added thrombin. These networks are tighter than would be expected from the initial rate of fibrinogen activation. In this case an extremely porous network is probably formed initially, followed by formation of a secondary, superimposed network of a less porous architectural quality. The latter structure appears to be governed by the rate of indigenous generation in plasma of thrombin-like enzymes in combination with the particular type of fibrinmonomers being produced. In addition our findings establish the rules for proper determination of gel structures in clinical plasma samples. The sequelae of a variety of clot structures that may be formed in vivo are discussed. PMID- 7992254 TI - Coagulation inhibition capacities of low-molecular mass and unfractionated heparin, as determined by thrombin generation. AB - The common unfractionated heparin preparations (UFH) accelerate inhibition of most of the enzymes in the coagulation cascade, while low-molecular mass heparin (LMMH) mainly accelerates inhibition of activated coagulation factor X (FXa). The present study addresses the question of whether LMMH may be a weaker anticoagulant than UFH when the two preparations are added to plasma with equal FXa inhibitory activities. Normal and coagulation factor VIII (FVIII)-deficient plasma was used. Thrombin generation was determined by assaying the formation of the thrombin-antithrombin complexes (TAT) and of fibrinopeptide A (FPA), two parameters that showed a strong positive correlation. At a heparin concentration of 0.5 or 1.0 FXa-inhibiting IU/ml, the formation of TAT and FPA was substantial and always much more increased with LMMH than with UFH. At 4.0 FXa-inhibiting IU/ml, no FPA was generated, but traces of thrombin were. In recalcified FVIII deficient plasma (one of the batches containing FVIII antibodies), more TAT was formed with 0.1 FXa-inhibiting IU/ml LMMH than with UFH with the same FXa inhibiting activity. It is concluded that LMMH is a weaker anticoagulant than UFH, partly because of a poor thrombin inhibition capacity which facilitates acceleration of coagulation by FVIII activation and partly because of a poor inhibition of enzymes preceding the prothrombinase stage, both mechanisms leading to increased enzymatic activity above the prothrombin stage. As judged from the higher degree of thrombin generation with LMMH than with UFH, there is no support for the assumption that LMMH is as good an antithrombotic agent as UFH is, without reducing the haemostatic capacity as much as UFH does. PMID- 7992255 TI - Bioassay of procoagulant albumin in human plasma. AB - Procoagulant albumin (P-Al) is present in normal human plasma and increases monocyte and endothelial cell expression of tissue factor activity. To develop a bioassay for P-Al, we partially purified plasma from healthy volunteers and several patient groups using BaCl2 and (NH4)2SO4 precipitation. The samples were assayed for tissue factor (TF) inducing activity, expressed as a percentage increase compared to a serum-free media control. Over six months, the assay was reproducible in stored samples and in serial samples from normal volunteers. The plasma P-Al activities of 35 volunteers averaged 141 +/- 8.2% (SEM). There was no diurnal variation. There was no difference in the P-Al activity after a 12 hour fast and 2 hours after a large meal in 4 healthy volunteers. There was no increase in activity (r = 0.16) with the subject's age. The average activity from 16 poorly-controlled diabetics was 131 +/- 11% (SEM). No alteration in activity was seen with samples from patients with uremia, liver dysfunction, hemophilia, thrombotic events, or adenocarcinoma. These results indicate that P-Al activity can be bioassayed in individual patient samples; however, pathologic states associated with abnormal P-Al-induced tissue factor activity presently remain unidentified. PMID- 7992256 TI - Fibrinolytic system of cultured rabbit aortic endothelial cells. AB - The fibrinolytic system of rabbit aortic endothelial cells (RAECs) isolated from male New Zealand White rabbits was investigated. The components of the fibrinolytic system in the conditioned media (CM) were analysed by SDS-PAGE followed by fibrin autography and reverse fibrin autography. The major lytic zones appeared at 54 and 70 KD and minor lytic zones could be detected between 100 and 120 KD. A plasminogen activator inhibitor was localised at 50 KD. Addition of amiloride abolished the lytic zones at 54 KD and 100 KD. There was a time dependent increase in plasminogen activator and inhibitor activities as revealed by an assay involving plasminogen and chromogenic plasmin substrate. A plateau was reached after 16-20 hours. When mRNA obtained from RAECs cultured for 16 hours in serum free medium was analysed for the presence of specific messages of tissue type plasminogen activator (t-PA), urokinase type plasminogen activator (u-PA) and plasminogen activator inhibitor 1 (PAI-1) using human probes, weak specific binding could be seen for both t-PA and mu-PA while the PAI-1 probe gave a strong specific signal at 3.4 Kb and a weak signal at 2.3 Kb. Both thrombin (1U/ml) and endotoxin (100 ng/ml) increased the release of PAI-1 activity into CM significantly, while there was no significant change in PAs. The increase of PAI 1 was reflected by increased PAI-1 mRNA levels. The data suggests that rabbit ECs can be used to investigate endothelial cell mediated fibrinolysis and supplement results obtained in investigations employing the rabbit as an in vivo animal model to study the fibrinolytic system. PMID- 7992257 TI - Daily variations of platelet aggregation in relation to blood and plasma serotonin in diabetes. AB - The circadian rhythms of platelet aggregation in the whole blood and platelet rich plasma-PRP and plasma serotonin were studied in healthy volunteers (n = 10) and diabetic patients (type II diabetes mellitus n = 12). Platelet aggregation in the whole blood induced by collagen (2 micrograms/ml), ADP (10 microM), arachidonic acid (0.5 mM) and epinephrine (10 microM), and in PRP induced by collagen (2 micrograms/ml), ADP (5 microM), arachidonic acid (250 microM), epinephrine (10 microM) and serotonin-5-HT (1 microM) was measured at 7:30, 11:30, 17:00, 23:00, 4:00 and 7:00. In healthy subjects collagen- and ADP-induced platelet aggregation in the whole blood was significantly lower at 23:00 and 4:00 when compared to values at 7:30. In PRP normal and diabetic platelet response was the lowest during the night. Diabetic platelets exhibited an enhanced response to 5-HT starting from 17:00 until 4:00 when compared to 7:30. 5-HT-induced platelet aggregation was found to be significantly higher throughout the study in DM patients over controls in parallel to plasma 5-HT. In healthy volunteers plasma 5 HT was higher at 17:00 when compared to baseline values, whereas in DM patients plasma 5-HT was elevated starting from 17:00 until 4:00. An enhanced response of diabetic platelets to 5-HT together with elevated plasma 5-HT levels may contribute, at least partly, to the pathogenesis of diabetic vasculopathy and 5HT2 receptor blockers may be of value in DM patients. PMID- 7992258 TI - Plasma TFPI activity after intravenous injection of pentasaccharide (PS) and unfractionated heparin in rabbits. AB - Tissue Factor Pathway Inhibitor (TFPI), is known, to be released in plasma after injection of intravenous or subcutaneous injection of heparin or low molecular weight heparin (1,2). Addition of protamine or polybrene in plasma can neutralize anticoagulant effects of heparin in vitro but not completely ex vivo in patients treated with heparin (3). It was believed for many years that this post-heparin anticoagulant effect was due to another activity released by heparin. More recently it has been shown that post-heparin anticoagulant effect could be inhibited by anti-TFPI antibodies (4). Since we have shown in a previous work (5), that in healthy volunteers, pharmacokinetics of TFPI were more closely related to anti IIa activity than anti Xa activity we hypothesized that fragments with anti-IIa activity may be required for this release, possibly from vascular wall. In order to determine if a very low molecular weight glycosaminoglycan can release TFPI in plasma, in the present study, we compared plasma TFPI amidolytic activity after intravenous injection in rabbits of pentasaccharide (PS), a synthetic fragment of very low molecular weight and with a strong and exclusive anti Xa activity, and unfractionated heparin (UFH). PMID- 7992259 TI - [Norwegian infection control in an international perspective]. PMID- 7992260 TI - [Reform or oblivion. Psychiatric long-term patients; life and treatment outside institutions]. PMID- 7992261 TI - [Disability as a paradox of health]. PMID- 7992262 TI - [Estrogen--good for the heart(?)]. PMID- 7992263 TI - [Attitudes of Norwegian general practitioners to prescription of estrogens 1990 92]. AB - In order to investigate the attitudes towards the prescription of hormone replacement therapy in menopausal and postmenopausal women, a questionnaire was mailed to two random samples of Norwegian general practitioners. The first sample (n = 340) was investigated in 1990, just before a national consensus conference on the use of oestrogens, the second (n = 240) one year after the conference. Nine short case stories were presented and the doctors indicated their attitudes to oestrogen prescribing in each case. Four items were systematically investigated: climacteric symptoms, smoking, risk of cardiovascular disease and osteoporosis. In general, a restrained attitude towards the prescribing of oestrogen was found. Smoking and a family history of cardiovascular disease reduced the willingness to prescribe. The doctors had more patients on oestrogen treatment in 1992 than in 1990. In general, the answers indicate a more liberal attitude to replacement therapy in 1992, but the pattern of willingness to prescribe remained unchanged. Female physicians showed greater willingness to prescribe oestrogen than their male colleagues did, and were more updated on contraindications. PMID- 7992264 TI - [New cases of HIV infection. Estimation of the time of transmission]. AB - During 1991 and 1992, 107 HIV infections were diagnosed at Ulleval hospital, Oslo. Previously collected serum specimens from 53 of these persons were tested with different anti-HIV and HIV antigen tests. Some of the sera were also examined for HIV RNA using PCR. Based on these results, the intervals between the last HIV negative and the first positive samples, and between the first HIV positive sample and the HIV diagnosis, were calculated. 38 persons had delivered HIV negative samples before their first positive sample. In addition, eight persons had a sample with serological markers of recent infection. For these 46 persons, the median time between the last HIV negative sample and the diagnosis was one year. 36 of them were HIV negative three years before diagnosis. For 19 persons, markers of HIV infection were detected in samples taken before the disease was first diagnosed. For two persons HIV markers were present in samples taken as early as 1986. PMID- 7992265 TI - [Bacteremia at a medium-sized Norwegian hospital]. AB - This report, which is based on laboratory reports and patient records, covers the epidemiology, etiology and antibiotic susceptibility of all bacteremic episodes at a community hospital during 1988-90. The overall incidence was eight episodes per 1000 patient admissions, though this figure varied considerably between departments and between age groups. Most organisms were community acquired, and we had few Klebsiella spp., Pseudomonas spp., anaerobic bacteria, fungi and polymicrobial episodes. There were fewer antibiotic resistant strains than reported from outside Scandinavia. The combination of benzylpenicillin and aminoglycoside (plus metronidazole in surgical wards) has a broad enough spectrum of activity for 95% of our patients with sepsis of unknown origin. Thus, our rather "old-fashioned" prescribing policy, with the new and broadspectrum cephalosporins and betalactam drugs constituting only a minor part, is still good practice. The study also shows that cumulative reports issued by the local microbiological laboratory bring awareness to these issues and affect the prescribing pattern in a positive way. PMID- 7992266 TI - [Diet therapy of hypercholesterolemia. Can the diet of persons who already follow a cholesterol-lowering diet be further improved by guidelines given by a clinical nutritionist?]. AB - The objective of the study was to investigate whether expert advice from a clinical nutritionist improves the diet of patients who have previously been instructed by health professionals to follow a lipid-lowering diet. We investigated dietary composition before and after dietary intervention by a clinical nutritionist in 46 individuals, aged 33 to 65 years, with primary hypercholesterolemia. After intervention, there was a 25% reduction in the intake of saturated fat and of cholesterol (p < 0.0001) and an 65% elevation of the P/S ratio (p < 0.05). Percentage of energy from fat remained unchanged. The diet of patients who are already following a lipid-lowering diet can be improved by expert advice from a clinical nutritionist, and they easily adjust to new habits. PMID- 7992267 TI - [Biological background of clinical bone transplantation]. AB - The biologic incorporation of bone grafts into host bone is dependent upon the type of graft, but the aim in all cases is to replace the graft with host bone by bone resorption and new bone formation. This is best achieved by transplanting fresh autogeneic bone. Allogeneic bone grafts are less efficient because of immunological reactions to the grafts, but they are the only alternative in clinical practice. There are several methods of preparing the allogeneic grafts to make them more suitable for clinical use, e.g. deep-freezing, freeze-drying, or demineralization. Experimentally attempts have been made to reduce the immunological reactions to allogeneic bone, or to combine the graft with bone inducing substances. The basic knowledge of bone transplant biology has improved greatly in recent years, but is still inadequate to achieve an improvement in the established clinical practice. PMID- 7992268 TI - [The polycystic ovarian syndrome. New physiopathological theories]. AB - Although the polycystic ovarian syndrome was first described in 1935, controversies regarding the pathophysiological mechanism still persist. The pathogenesis seems multifactoral and the events leading to clinical manifestation of the disease can be triggered or can originate in different organ systems, such as the central nervous system or the ovary itself. The syndrome can originate from excess fat tissue and hyperinsulinemia, or may be a result of an increase in growth factors acting on the ovary. The current view is that the full expression of the polycystic ovarian syndrome is probably the result of several entities. PMID- 7992269 TI - [Nasal polyps and chronic sinusitis as a possible adverse effect of non-selective beta blockers]. AB - Five patients presented with unusually severe and therapy-resistant rhinitis, sinusitis, and nasal polyps. Long courses of antibiotics did not cure the sinusitis, and recurrences appeared soon after surgical intervention. The patients used non-selective beta blockers for hypertension or as secondary prophylaxis after cardiac infarction, either timolol (n = 4) or propranolol (n = 1), and the nasal problems developed with a latency ranging from a few days up to four years of beta blocker use. Two of the patients discontinued the beta blocker for reasons relating to cardiovascular status and experienced complete remission of the nasal problems without further treatment. In the three remaining patients the therapy was withdrawn. The symptoms cleared within weeks, and did not recur. The patients who needed beta blockade experienced no recurrence when put on beta 1-selective blocker (metoprolol or atenolol). PMID- 7992270 TI - [Mental Health's hot line. A report from the first year of the service]. AB - In 1992, Mental Health Norway, a national organisation of psychiatric patients, started a telephone-service for persons in difficult situations. The service is free, and operates all day and night. The counsellors are specially selected lay persons. They are supervised by the head of the project and by a psychiatrist. During the first year more than 20,000 calls from all over the country were answered. The callers have been registered both demographically and according to the problems presented. The findings are reported, and problems, such as thoughts of suicide, are described in detail. The author stresses the importance of regular supervision of the counsellors, and mentions the possibility of extending the service. Some difficulties in measuring the efficiency and the effects of a service of this kind are also discussed. All the same, a telephone service which offers a personal talk here and now or establishes contact with professionals when essential is considered justified. PMID- 7992271 TI - [The physiological and pathophysiological significance of endothelins]. AB - Endothelin-1 (ET-1) is a vasoconstrictor peptide of endothelial origin belonging to a family of four isopeptides consisting of ET-1, ET-2, ET-3, and vasoactive intestinal constrictor also called ET-4. These peptides show considerable homology with the sarafotoxins which are cardiotoxic molecules present in the venom of the snake Israeli burrowing asp. ET-1 is the most potent vasoconstrictor known, ten times more potent than angiotensin II. It is synthesized in response to stress, hypoxia, and other vasoactive substances. The physiological role of the endothelins and site of synthesis for ET-2 and ET-3 are still unknown. Two endothelin receptors have been cloned. Elevated plasma levels of ET-1 have been measured in patients suffering from various diseases such as myocardial infarction, cardiogenic shock, septic shock, renal failure, subarachnoid haemorrhage and pre-eclampsia. ET-receptor antagonists and ET-1 synthesis inhibitors are now available. It has been shown that these inhibitors, and also ET-1 antibodies, ameliorate the consequences of severely impaired blood flow in the kidney and in the brain. In animals, infusion of endothelin antibody has been shown to limit the size of myocardial infarction. ET-1 inhibitors can be expected to play a therapeutic role in the future. PMID- 7992272 TI - [Global transmission of Salmonella--increased risk in Norway. Interdisciplinary measures are necessary to maintain Norway's favourable situation]. AB - Over the last 20 years, Salmonella infections in humans have increased considerably in the industrialized world, including Norway. The situation has been characterized as a serious problem, with considerable economic, political and public health implications. In contrast to the situation in most other countries, a large majority of the Norwegian patients have contracted the infection abroad. The endemic level of salmonellosis in Norway is low, and the prevalence of Salmonella in Norwegian food products is negligible. Appropriate intersectorial actions are required to maintain Norway's favourable status. Such actions include: preventing import of infected food, feed, and live animals; ensuring good hygienic practices at all stages of production, processing, and preparation of food; maintaining the present good health status of meat producing animals; providing consumers with drinking water of adequate hygienic quality; and intensifying national and international collaboration to prevent and control salmonellosis. PMID- 7992273 TI - [Esophageal lesions induced by iron tablets]. AB - Oesophageal injury in the form of ulcers, with deposition of iron salts, was diagnosed histologically in 12 patients over a 3-years period. One patient died following perforation of the oesophagus. Not in any of the patients was the use of iron tablets thought of clinically as a possible cause of the lesion. This appears to be the most likely explanation, however, owing to the fact that the use of iron sulphate tablets of sustained release type was reported by ten out of 12 patients. The patients were all elderly and the majority were bedridden. Any gain from using iron medication in the elderly and bedridden should be weighed against the potential danger related to the use of iron sulphate tablets of sustained release type. PMID- 7992274 TI - [Electromagnetic therapy for patients with intermittent claudication--is it effective?]. AB - A treatment based on electromagnetic principles (Elmedistraal) has been tested on 12 patients with intermittent claudication. What initiated this investigation was the publicity in the media around this treatment and its supposedly positive effect on peripheral circulation. 12 patients received ten placebo and ten active treatments. The patients were thus their own control. We looked for changes in clinical signs, ankle/arm pressure index (ultrasound Doppler) and maximal walking distance (treadmill). The patients reported changes in symptoms by means of a visual analog scale. In this study neither subjective nor objective effects of treatment with Elmedistraal could be documented in patients with claudication. PMID- 7992275 TI - [Norwegian infection control in the new Europe]. AB - Infectious diseases are still a major health problem world wide. In Europe, however, and in Norway in particular, infectious diseases have not been a threat to public health for several years. In this paper, some of the major events in the European region which could have an impact on public health are discussed. These events include the extensive migration of people in the European region, military conflicts in former Yugoslavia, serious economic and social problems in the former Soviet-Union, and the expansion of the European Union (EU). Increased passage across borders of people and food may, in the worst case, represent a threat to public health. The paper also deals with the status of the different elements of the Norwegian health care system involved with infectious disease control, and with the parts of this system that should be improved, in order to adjust to the new epidemiologic situation that may be encountered in the European region. PMID- 7992276 TI - [The extent of disability pensions based on educational background. Disability pensions in the period 1967-1992 in a group born 1949 in Bergen]. AB - The authors discuss recruitment to disability pension in groups of former pupils of different types of school in the school system in Bergen in the 1950s. The study is based on a cohort of 1,570 persons, all live births from 1940 of the mothers then residing in Bergen. This birth-cohort was followed up in the school system in Bergen at the age of 14 years and up to the end of 1992. Information on disability pensions was extracted from the files of the National Insurance Administration for the years 1967-92. The prevalence of disability pension of former pupils of different types of school reached a peak at the end of 1992, i.e. at the age of 52 years, as follows: Former pupils of the regular secondary schools, i.e. junior high school and continuation school, 6.8% and 12.7% respectively, former pupils of elementary school classes for slow learners 25.9%, of special schools for the educable mentally retarded 59.6% and for those receiving the services for the mentally retarded, 100%. PMID- 7992277 TI - [Use of disability pensions. Disability pensions from 1967 to 1992 in a group from Bergen born in 1940]. AB - The authors describe the medical conditions (expressed by ICD-codes) leading to a disability pension in a cohort of 1,570 persons born in the year 1940. Information on disability pensions was extracted from the files of the National Insurance Administration for the years 1967-92. The disability diagnoses varied during the period 1967-92. Diagnoses during the first years reflect conditions that caused disability of young persons. Later on, diagnoses of "traditional" mental and organic diseases were used. Gradually other diagnoses, including alcoholism also appeared. This was a consequence of a broadening in the 1970s of the medical criteria for occupational disability. In recent years, disability diagnoses related to unspecific conditions are seen, particularly diagnoses reflecting symptoms associated with the musculosceletal system. These disability diagnoses were used in the case of about 30% of the women in the cohort who became new pensioners during the period 1988-92. PMID- 7992278 TI - [Oligophrenia as a disability diagnosis. Disability pensions in the period 1967 1992 in a group from Bergen born in 1940]. AB - The authors discuss the use of unspecified oligophrenia as a diagnosis for disability pension, and draw attention to unrecognized oligophrenia. The study is based on a cohort of 1,570 persons, comprising all live births from 1940 of the mothers then residing in Bergen. The cohort was followed up in the school system in Bergen at age 14 years, again at age 30 years (1971) and up to the end of 1992. Relevant information on disability pensions was extracted from the files of the National Insurance Administration. The results of medical and psychological examinations in 1971 of a random sample of the cohort are also included. In the cohort 180 persons became new pensioners during the years 1967-92. Of these 10.6% were diagnosed as disable due to oligophrenia. In the sample 69.6% of the IQ group 55-69 were receiving a disability pension, two thirds with a diagnosis of oligophrenia. In the IQ-group 70-84, 46.4% had a disability pension, one third with the diagnosis oligophrenia. These findings suggest that the use of oligophrenia as a disability diagnosis is less frequent than the prevalence of oligophrenia would in fact seem to justify. PMID- 7992279 TI - [The specialty orthopedic surgery. Lack of interest for and prevalence in the surgical specialties]. PMID- 7992280 TI - [CT and pelvimetry]. PMID- 7992281 TI - [Norwegian psychiatry and Nazism]. PMID- 7992282 TI - [On women in the medical profession]. PMID- 7992283 TI - [Is it necessary to be burned first to avoid the fire?]. PMID- 7992284 TI - [If the abortion law were practised as the Parliament required]. PMID- 7992285 TI - [Tourette syndrome and related conditions]. PMID- 7992286 TI - [High-dose autologous stem cell support in malignant diseases--an established method, uncertain indication]. PMID- 7992287 TI - [Infusion of hematopoietic stem cells from the blood. Simpler and better than bone marrow transplantation?]. AB - Infusion of haematopoietic stem cells, either autologous or allogeneic, allows treatment of malignant diseases with marrow ablative doses of cytostatics or whole body irradiation. Hospitalization and general anaesthesia is necessary for bone marrow harvesting, while the harvest of peripheral stem cells may be performed without hospitalization. Mobilization of haematopoietic stem cells from the bone marrow to peripheral blood, followed by cytapheresis and harvesting of the stem-cell containing fraction is a promising alternative to the harvest of marrow. We have tried this in one patient with advanced acute myeloid leukaemia and discuss our experience and that of others. PMID- 7992288 TI - [Patients with burns admitted to hospitals in 1992. Fewer cases and shorter length of stay also in Norway?]. AB - Patients admitted for care of acute burns in Norway in 1992 were compared with patients in an earlier national survey in 1977. In 1992, 635 patients were admitted for acute burns in Norway, 20% less than in 1977. 8,975 hospital days were spent on care of acute burns, a 45% reduction compared with 1977. 58 patients (10% of all burn cases admitted to hospital) were referred to the National Burn Centre in Bergen. The number of deaths from fire and burn injury was similar to the number in 1977 (68 persons). Despite a moderate reduction in the total number of burns we found no evidence of a significant reduction in the number of severe burns. To achieve optimal functional and cosmetic results, extensive burns still deserve the special care offered in a regional Burn Centre. PMID- 7992289 TI - [Tourette syndrome in children. An analysis of everyday problems--neurology or emotional conflicts?]. AB - Over a three year period, 109 children aged 5-17 were diagnosed as having Tourette syndrome. They were all evaluated by a team composed of persons with backgrounds in special education, physiotherapy or neuropsychology, and a paediatrician with experience in child neurology. All the children satisfied the criteria of several motor tics and at least one vocal tic lasting more than one year. Besides the tics the most common symptoms were attention deficit disorder and motor hyperactivity. These symptoms were present in 79 children (73%). 42 children (39%) met the criteria for minimal brain dysfunction. Problems relating to attention, activity, perception, motor control and language are generally considered to be part of a neurological dysfunction. We also investigated the children's emotional profile by looking into factors such as aggression, fluctuations of mood, peer relationships and impulsiveness. More than half of the children experienced serious problems in these areas. We believe that emotional problems of this nature are an integral part of their neurological dysfunction and that they can seldom be attributed to psychological factors in their families or to other events related to everyday life. PMID- 7992290 TI - [Percutaneous endoscopic gastrostomy. Experiences with the first 10 cases in a medical department]. AB - Enteral nutrition has many advantages over parenteral nutrition and is being increasingly used. Percutaneous endoscopic gastrostomy is performed under local anaesthesia by means of a gastroscope inserted for 15-20 minutes. From January 1993 til January 1994 we performed ten percutaneous endoscopic gastrostomies in patients suffering mainly from stroke and dysphagia. The article includes a description of the method and the results. The mean application time for the gastrostomies was 67.9 days (14-238 days). No serious complication was observed, two local wound infections were noted. It is concluded that percutaneous endoscopic gastrostomy is a safe and efficient method for enteral nutrition. The method seems to have few complications, is cheap and is simple to perform. PMID- 7992291 TI - [Selective catheterization of the inferior petrosal sinus]. AB - The inferior petrosal sinus is a dura sinus which traverses laterally and dorsally from the dorsal aspect of the cavernous sinus. It represents the nearest catheterization point for blood sampling from the pituitary gland. Inferior petrosal sinus venous sampling is used for diagnosis and lateralization of ACTH secreting and growth hormone-producing hypophyseal adenomas. It is also used in the differential diagnosis of ectopic production of ACTH or other similar peptides. We briefly describe the anatomy of the inferior petrosal sinus and the catheterization technique, based on our experience from 15 patients. The endocrinological results are published in a separate article. PMID- 7992292 TI - [Analysis of blood from the inferior sinus petrosus in patients with Cushing syndrome and acromegaly]. AB - Bilateral catheterization of sinus petrosus inferior was performed in ten patients with Cushing's syndrome and five patients with acromegaly. This was done in order to secure the diagnosis (Cushing's syndrome) and localize an adenoma (Cushing's syndrome and acromegaly). Blood from sinus petrosus inferior on both sides and from the peripheral vein was analyzed for concentration of ACTH or growth hormone after injection of ACTH-releasing hormone and growth hormone releasing hormone respectively. The quotient between the ACTH concentration in blood from sinus petrosus and peripheral blood determines the diagnosis in Cushing's syndrome and the quotient between the concentration of ACTH or growth hormone between right and left sinus petrosus determines localization of the pituitary adenoma. Correct diagnosis and localization of ACTH-producing pituitary adenoma was found in eight of ten patients with Cushing's syndrome. One result was doubtful and one was wrong. In four patients with Cushing's disease (ACTH producing adenoma) magnetic tomography (MT) was negative, but catheterization showed the presence of adenoma. In acromegalic patients, correct localization of the adenoma was determined in two out of five patients. In the other three patients, anatomical difficulties prevented satisfactory interpretation. PMID- 7992293 TI - [A comparison between lovastatin and pravastatin--effects on lipids, sleep and quality of life in primary hyperlipidemia]. AB - The efficacy and safety of treatment with recommended doses of lovastatin (20, 40 and 80 mg/day) and pravastatin (10, 20 and 40 mg/day) were compared in 48 men and women with primary hyperlipidemia and LDL-cholesterol > or = 4.1 mmol/l following dietary intervention. Each dose was taken for six weeks in this double-blind, parallel, randomized study. Lovastatin was found to reduce LDL-cholesterol by 22 37% and pravastatin by 18-26%. HDL-cholesterol levels increased and triglyceride levels decreased to the same extent in both groups. The number of patients who reported adverse events in the course of the study was small. No clinically significant changes occurred in laboratory tests, nor in sleep scores obtained from a standardized questionnaire. Neither drug had any effect on the responses to a quality of life screening questionnaire, nor were any significant changes in depressive symptoms seen during the 18 weeks of treatment. PMID- 7992294 TI - [The significance of proteoglycans in several diseases]. AB - A prominent feature in several diseases is the accumulation of connective tissue. The ultimate result of high levels of extracellular matrix is organ failure and death, evident in diseases such as liver fibrosis, diabetes and amyloidosis. Among the extracellular matrix components, proteoglycans play a basic role in several pathological conditions. In the development of atherosclerosis they provide an anchor for lipoprotein lipase on the endothelial wall, sequester lipoproteins in the subendothelial matrix and present lipoproteins to macrophages. In diabetes these proteoglycans have a lower charge, such that the network has a reduced capacity to retain negatively charged proteins. In fibrosis and amyloidosis the synthesis of proteoglycans and matrix is increased and large amounts are deposited at the expense of tissue-specific cells. Some of the conditions mentioned can be ameliorated by changes in the diet. PMID- 7992295 TI - [Illness caused by water-based paints?]. AB - Illness caused by the indoor environment is a challenging and complicated field to investigate. Emissions from paints may contribute to the problems. Several components of water-based paints evaporate for a long time after painting, and some of them may affect human biology. We describe one patient who has experienced symptoms caused by water-based paint. Different reaction mechanisms may be involved, and these are discussed. Components which may elicit biological effects are listed and discussed. Physicians should be aware of the possibility that a few patients may suffer from illness caused by emissions from modern paints. PMID- 7992296 TI - [The chemical working environment among car painters in Bergen]. AB - Official guidelines have been prepared for the working environment in Norwegian spraylacquering garages, in order to reduce the incidence of symptoms and diseases related to exposure to organic solvents. 11 garages were visited to see if the guidelines were being followed. All the sprayers (n = 28) were examined by questionnaire about the occurrence of acute symptoms connected to the central nervous system, the skin, the eyes and the airways during work, and about their use of personal protective equipment. All the garages had specially ventilated rooms for the lacquering procedure, and all the workers used personal respiratory protective equipment. The sprayers did not report more acute symptoms than a control group of office workers employed in the same companies. PMID- 7992297 TI - [The decision-making process and information needs among women seeking abortion. Results from 2 studies conducted with a 10-year interval, 1983-93]. AB - The decision-making process and need for medical information during the consultation prior to abortion were examined among 183 women who sought abortion in 1983 and 160 in 1993 at the Department of Gynaecology, University Hospital, Trondheim, Norway. The father of the foetus participated significantly more often in the decision-making process in 1993 than in 1983. The final decision was taken either by the woman alone or together with the father of the foetus. More than 85% of the women had decided to terminate the pregnancy before requesting an abortion at the pre-abortion visit. Few women were under pressure when they decided to terminate the pregnancy. More women were under pressure to continue the pregnancy to term than to terminate (p < 0.05). Norwegian abortion law guarantees the right to medical information during the pre-abortion consultation. The general practitioners involved scored higher in 1993 compared with their colleagues in 1983, since they satisfied the demands of abortion-seeking women for medical information concerning the surgery and possible complications. PMID- 7992298 TI - [The native country of many of the Norwegian immigrants]. PMID- 7992299 TI - [Preparation prior to punishment--a medical issue?]. PMID- 7992300 TI - [What attitude do physicians have to risk?]. PMID- 7992301 TI - [A simple instruments for blood glucose measurement]. PMID- 7992302 TI - [Education of the elderly--help to self-help]. PMID- 7992303 TI - [Malignant lymphomas in dogs: a review with reference to non-Hodgkin lymphoma in man]. PMID- 7992304 TI - [Tumor cells on the inside and tumor cells on the outside. A contribution to the diagnosis and elucidation of the pathogenesis of mammary tumors in dogs]. AB - This review discusses some recent experience with intra- and extracellular components of tumours as markers for tumour diagnosis. Intermediate filaments are cytoskeletal proteins of either epithelial or mesenchymal cells. Antibodies raised against human intermediate filament proteins cross-react with their canine counterparts. A study of the presence and distribution of intermediate filaments in normal mamma and mammary tumours of dogs showed that they do not contribute to a more adequate classification of the tumours. However, the presence of vimentin in epithelial tumour cells may be a marker of malignancy. Proteoglycans are extracellular matrix proteins, containing long chains of glycosaminoglycans (GAGs). Analysis of the presence of GAGs in canine mammary tumours showed that accumulation of chondroitin sulfate, frequently of an abnormal type, was a predominant finding in all tumour types, but not in normal mamma, and was not related to biological behaviour. Although demonstration of the before-mentioned tumour components does not help tumour diagnosis, it may contribute to the elucidation of the development of such tumours as the complex and mixed adenomas of the mamma of which cartilage and bone are important constituents of unknown origin. PMID- 7992305 TI - [Immunotherapy of tumors in agricultural domestic animals]. PMID- 7992306 TI - [Oncology, pathology and companion animal practice]. AB - A review of research in veterinary oncology, as executed in Amsterdam and Utrecht, is presented. Also an inquiry into the cooperation between oncologist, pathologist and practitioner is discussed. It is concluded that microscopic tumour diagnosis is practized at too low a scale (+/- 30%). Veterinary oncology has significance both from the veterinary and the comparative (model) point of view. Etiologic-pathogenetic and biologic-therapeutic aspects are studied in a multidisciplinary way. Intercellular communication, growth factors and intercellular matrix are items of present and future research. Molecular-genetic research is in progress. Prevention of mammary tumours by ovariectomy (dog, cat) and of malignant lymphoma (cat) by fighting FeLV seems promising. PMID- 7992307 TI - [What is cardiomyopathy?]. PMID- 7992308 TI - Inhibition of Na(+)-glucose cotransport in kidney cortical cells by cadmium and copper: protection by zinc. AB - Properties of the inhibition of Na(+)-glucose cotransport by Cd2+ in mouse kidney cortical cells have been determined. In no case was any inhibition observed before 3 hr. The extent of inhibition was dependent upon both the concentration of Cd2+ and the length of exposure. Kinetic studies showed that metallothionein mRNA induction by Cd2+ was initiated within 1 hr after incubation with Cd2+ began and peaked by 3-6 hr. Metallothionein protein increased more slowly, beginning at 3 hr and continuing for at least 9 hr. The protein had both Cd2+ and Zn2+ bound to it throughout this period. Nevertheless, a pool of nonmetallothionein Cd2+ appeared after 3 hr, coinciding with the onset of inhibition of Na(+)-glucose cotransport, and increased over the next 9 hr. Pretreatment of cells with Zn2+ protected them from the effects of Cd2+ on Na(+)-glucose cotransport. It delayed the onset of inhibition of transport as well as the extent of inhibition. Detailed analysis of the distribution of Cd2+ and Zn2+ in the soluble fraction of these cells showed that the concentration of non-metallothionein bound Cd2+ was not suppressed by the presence of Zn-metallothionein after the onset of exposure to Cd2+. Incubation of cells with larger concentration of Zn2+ and Cu2+ also inhibited Na(+)-glucose cotransport. PMID- 7992309 TI - Monocrotaline alters type II pneumocyte morphology and polyamine regulation. AB - Lungs from monocrotaline (MCT)-treated rats exhibit altered polyamine metabolism and content. One of the prominent morphological abnormalities in MCT-treated lungs is a decrease in population density of type II pneumocytes. Against this background, the present study tested the hypothesis that failure to maintain normal population density of type II pneumocytes is associated with MCT-induced derangements in polyamine biosynthesis and/or transmembrane polyamine transport. After a 24-hr treatment, cultured type II pneumocytes exhibited numerous vacuoles at the highest dose of 3.2 mM MCT but not at the lower dose of 1.6 mM MCT. Intracellular spermidine content was significantly reduced at the highest dose of MCT. Relative to controls, the abundance of mRNA for both ornithine decarboxylase, and S-adenosylmethionine decarboxylase, key regulatory enzymes in polyamine synthesis, was not altered. However, the activities of both of these enzymes were dramatically reduced. Increased mRNA for the catabolic polyamine enzyme, spermine/spermidine-N1-acetyltransferase (SAT), paralleled significant increases in SAT activity. MCT also caused a concentration-related inhibition of spermidine uptake in type II cells, characterized by a fourfold decrease in Vmax with little change in Km. These results show that MCT alters type II pneumocyte polyamine regulatory mechanisms and may help explain the decreased population density of type II pneumocytes in MCT-treated rats. PMID- 7992310 TI - Increases in the number of reactive glia in the visual cortex of Macaca fascicularis following subclinical long-term methyl mercury exposure. AB - The number of neurons, astrocytes, reactive glia, oligodendrocytes, endothelia, and pericytes in the cortex of the calcarine sulcus of adult female Macaca fascicularis following long-term subclinical exposure to methyl mercury (MeHg) and mercuric chloride (inorganic mercury; IHg) has been estimated by use of the optical volume fractionator stereology technique. Four groups of monkeys were exposed to MeHg (50 micrograms Hg/kg body wt/day) by mouth for 6, 12, 18, and 12 months followed by 6 months without exposure (clearance group). A fifth group of monkeys was administered IHg (as HgCl2; 200 micrograms Hg/kg body wt/day) by constant rate intravenous infusion via an indwelling catheter for 3 months. Reactive glia showed a significant increase in number for every treatment group, increasing 72% in the 6-month, 152% in the 12-month, and 120% in the 18-month MeHg exposed groups, and the number of reactive glia in the clearance group remained elevated (89%). The IHg exposed group showed a 165% increase in the number of reactive glia. The IHg exposed group and the clearance group had low levels of MeHg present within the tissue; however, the level of IHg was elevated in both groups. These results suggest that the IHg may be responsible for the increase in reactive glia. All other cell types, including the neurons, showed no significant change in number at the prescribed exposure level and durations. The identities of the reactive glial cells and the implications for the long-term function and survivability of the neurons due to changes in the glial population following subclinical long-term exposure to mercury are discussed. PMID- 7992311 TI - Platelets and alpha-naphthylisothiocyanate-induced liver injury. AB - Administration of alpha-naphthylisothiocyanate (ANIT) to rats results in periportal cholangiolitic hepatopathy. Inflammation is a hallmark of the liver injury, and expression of toxicity is dependent on blood neutrophils. The role of other cellular mediators of inflammation in ANIT-induced hepatic insult is unknown. We hypothesized that platelets participate in the expression of ANIT hepatotoxicity. To test this, circulating platelets were decreased by administration of anti-rat platelet serum (PAb) prior to treatment of rats with ANIT. The PAb treatment regimen effectively reduced circulating thrombocytes over the course of the experiment. Twenty-four hours after oral ANIT administration, rats were euthanized and liver injury was estimated by increases in serum alanine aminotransferase (ALT) and gamma-glutamyltransferase (GGT) activities. Cholestasis was assessed by measurement of serum total bilirubin concentration and bile flow. Reduction in platelet numbers was associated with attenuation of the increases in plasma ALT activity and bilirubin concentration seen after ANIT administration. However, PAb treatment did not attenuate the increase in plasma GGT, a marker of biliary epithelial cell injury. ANIT-induced changes in platelet function were assessed by evaluating platelet aggregation responses in platelet rich plasma from rats treated with ANIT in vivo. ANIT treatment modestly decreased ex vivo platelet aggregation in response to ADP and collagen stimuli. To address further the role of platelet-derived cyclooxygenase products in ANIT hepatotoxicity, rats were treated with aspirin or ibuprofen. Neither pretreatment ameliorated ANIT-induced hepatic insult. These results suggest that platelets contribute to the expression of ANIT-induced liver injury, but they do not appear to act through the production of cyclooxygenase metabolites. PMID- 7992312 TI - Beta-adrenergic receptor overexpression in the fetal rat: distribution, receptor subtypes, and coupling to adenylate cyclase activity via G-proteins. AB - Biogenic amines are hypothesized to play a role in the control of cell differentiation. We assessed the development of beta-adrenergic receptors and their linkage to adenylate cyclase activity in order to determine whether catecholaminergic cell signaling can take place early in development. On Gestational Day 12, beta-receptors were present in rat embryo in concentrations comparable to those in mature adrenergic target tissues; the concentrations climbed fivefold by Gestational Day 18. beta-Receptor expression was higher in liver than in heart and brain, as identified both by binding to isolated membrane preparations and by receptor autoradiography; nevertheless, receptor distribution was quite widespread, with labeling visible throughout the fetus. Receptor subtype selectivities (beta 2 in liver, beta 1 in heart, predominantly beta 2 in whole fetus) were already in place in early development, but receptor coupling to adenylate cyclase via G-proteins showed substantial developmental changes. Agonist-induced displacement of radioligand binding showed little or no GTP sensitivity on Gestational Day 12, suggesting relatively poor receptor linkage to Gs. In contrast, by Day 18, GTP produced a large shift in the agonist displacement curve. Receptor stimulation of adenylate cyclase by isoproterenol also showed a developmental spike by Gestational Day 18; the pattern for isoproterenol stimulation was distinct from the ontogeny of adenylate cyclase itself and from stimulation by forskolin-Mn2+ (which bypasses the need for receptors or G-proteins) or by fluoride (which activates G-proteins nonselectively). Thus, beta-receptors are highly expressed during fetal development and the receptors are readily capable of modulating intracellular cAMP production. Fetal catecholamines, which are produced and released by the adrenal medulla, extraadrenal chromaffin tissue, and cells that transiently express adrenergic phenotype, can thus have a direct impact on the differentiation of a wide variety of cells. PMID- 7992313 TI - Changes in alveolar lavage materials and lung microsomal xenobiotic metabolism following exposures to HCl-washed or unwashed crystalline silica. AB - Intratracheal exposures of rats to crystalline silica washed with HCl to remove iron contaminants have previously been shown to increase lung surfactant phospholipids (PL) and proteins and to alter the pulmonary microsomal cytochrome P450 system. We compared these effects of HCl-washed silica with those produced by exposures to unwashed silica and alumina. Both silica preparations produce increases in lung weights and alveolar lavage PL and proteins, but to different degrees. The increases produced by HCl-washed vs unwashed silica are lung weights, 2.2- vs 1.3-fold; lavage PL, 25.9- vs 3.7-fold; and lavage proteins, 11.1- vs 3.2-fold, respectively. Although the two silica particles increase lung microsomal protein concentrations (expressed per gram lung) by 50-60%, their effects on cytochrome P-450-mediated xenobiotic metabolism are quite different. Exposure to HCl-washed silica leads to a 2.3-fold increase in 7-ethoxyresorufin O deethylation, a reaction catalyzed by cytochrome P4501A1, and a 0.5- to 0.6-fold reduction in 7-ethoxycoumarin O-deethylation, a reaction which may be catalyzed by cytochrome P-4502B1. Unwashed silica does not alter the metabolism of either xenobiotic when results are expressed per milligram microsomal protein. Administration of alumina produces only minor increases in lung weight and lavage PL and no effect on microsomal xenobiotic metabolism. These results show that the increases in alveolar lavage PL and proteins induced by administration of unwashed silica are exaggerated by 3- to 7-fold if the silica is treated with HCl. Furthermore, exposure to HCl-washed silica results in significant alterations of the lung microsomal cytochrome P450 system, but the unwashed silica has little effect. Although the reason(s) for these different effects is not known, measurements of iron levels and formation of hydroxyl radicals using ESR demonstrate that there is more iron associated with the unwashed than with the HCl-washed silica. PMID- 7992314 TI - Additive binding of polychlorinated biphenyls and 2,3,7,8-tetrachlorodibenzo-p dioxin to the murine hepatic Ah receptor. AB - Fixed aliquots of both radiolabeled [3H]2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and hepatic Ah receptor from C57BL/6J mice were incubated competitively at 4, 23, and 30 degrees C with mixtures of 2,3,7,8-TCDD and several polychlorinated biphenyls (PCBs). The production of the radiolabeled receptor-ligand complex changed if the ligands were added sequentially, demonstrating that the competition between PCBs and TCDD for the Ah receptor in vitro is principally a kinetic rather than an equilibrium phenomenon and is irreversible on the time scale of our in vitro experiments. Examination of previous reports on the ability of TCDD, PCBs, and their mixtures to induce cleft palate in fetal mice suggests that the potency of receptor-ligand complexes is ligand-dependent. Receptor occupancy is not a sufficient condition for toxicity, and protection by one ligand against the toxic effect of a second, more potent one is only possible when a significant fraction of receptors is occupied. PMID- 7992315 TI - Clofibrate pretreatment diminishes acetaminophen's selective covalent binding and hepatotoxicity. AB - Peroxisome proliferators have been shown to diminish acetaminophen (APAP) hepatotoxicity (Biochem. Pharmacol. 43, 1395, 1992). To investigate the mechanistic basis for this protection CD-1 male mice were given corn oil or 500 mg clofibrate (CFB)/kg, ip, daily for 10 days. They were then fasted overnight and either killed without challenge or at 4 or 12 hr after challenge with 800 mg APAP/kg (in 50% propylene glycol). At 12 hr, hepatotoxicity was evidenced by elevated plasma sorbitol dehydrogenase and histopathology in corn oil but not in CFB-pretreated mice. At 4 hr after APAP treatment, hepatic glutathione (GSH) depletion and selective arylation of the major APAP target proteins were both greatly diminished by CFB pretreatment. Western blot analysis with the anti-58 antibody of liver cytosol from unchallenged mice showed no apparent changes in the levels of the 58-kDa major APAP target protein with CFB treatment. These findings suggest that protection could be the result of diminished net availability of generated electrophile. In vitro, measurements indicated that the specific activity in microsomes for APAP oxidation by cytochrome P450 was not changed by CFB treatment; whereas GSH S-transferase activity in cytosol was decreased by 25%. Pretreatment with CFB also produced a significant elevation in hepatic GSH. These studies indicate that protection by CFB might result from increased availability of hepatic GSH which could trap APAP electrophile nonenzymatically, thereby decreasing covalent binding and preventing toxicity. PMID- 7992316 TI - Limited effects of ozone exposure during pregnancy on physical and neurobehavioral development of CD-1 mice. AB - Only a few studies have attempted to assess in laboratory rodents the maternal toxicity and behavioral changes in offspring caused by prenatal exposure to ozone (O3). In particular, no data are available concerning the behavioral development of mouse offspring after maternal exposure, despite the fact that increasing use is made of this species in behavioral teratology studies for reasons both of economy and in order to increase the effectiveness of subsequent higher-tier studies (e.g., of treatment-genotype interactions). In the present work, female CD-1 mice were exposed during pregnancy (Days 7-17) to different O3 concentrations (0, 0.4, 0.8, or 1.2 ppm); to avoid confounding by postnatal maternal effects, all litters were assigned shortly after birth to foster dams neither treated nor handled during pregnancy. The dams' food and water intake and body weight gain were depressed in a concentration-dependent fashion. Tolerance to these effects developed during continuing exposure; such tolerance was faster in the case of food than water intake. Several measures of reproductive performance, such as proportion of pregnancies carried to term, litter size, sex ratio, frequency of stillbirth, and neonatal mortality, failed to show differences between control and O3 animals. Postnatal body weight gain was slightly but significantly depressed in the 1.2 ppm offspring. Otherwise, the somatic development of O3 pups was indistinguishable from that of controls, save for a delay in eye opening; this effect, however, failed to show a significant concentration dependence. Negative results were obtained in a wide range of assessments concerning (i) the development of various reflexes and responses ("Fox battery") from birth to Day 18; (ii) ultrasonic emissions on Postnatal Days 3, 7, and 11; and (iii) activity, habituation, response to an unfamiliar object, and hyperactivity produced by a monoaminergic stimulant (d-amphetamine) at 60-61 days. The present data differ from those of a previous study on rats raised by their biological mothers after gestational exposure to O3 (1 and 1.5 ppm), which showed a substantial impairment in somatic and neurobehavioral development (R. Kavlock, E. Meyer, and C. T. Grabowski, 1980, Toxicol. Lett. 5, 3-9). This difference, be it due to species factors, to postnatal maternal effects, or to the time of occurrence of maximal O3 effects (e.g., on food and water intake) after the onset of exposure and before adaptation or tolerance, may provide significant cues for the understanding of O3 effects in pregnant and developing organisms. PMID- 7992317 TI - Clearance of glutathione disulfide from rat mesenteric vasculature. AB - Organs of the digestive tract, including pancreas, small intestine, and colon, have mechanisms to modulate plasma thiol-disulfide balance. Because plasma glutathione disulfide (GSSG) concentration may be elevated from < 1 microM in control rats to over 25 microM during oxidative stress, we examined whether GSSG was cleared from rat mesenteric vasculature. When 100 microM GSSG was perfused through the gut via the superior mesenteric artery, an average of 45% was lost in a single pass. Results showed that gamma-glutamyltransferase (gamma-GT)-dependent and -independent mechanisms were involved in GSSG loss. Acivicin (AT125) treatment inhibited gamma-GT activity in the mesenteric vasculature by 94% and attenuated the loss of GSSG equivalents by 44%. These results supported a role for gamma-GT in GSSG loss from the mesenteric vasculature but indicated that still other mechanisms were involved in GSSG clearance. Elevations of portal levels of glutathione (GSH) and the mixed disulfide of cysteine and GSH (CySSG) also occurred with vascular GSSG perfusion and could account for about 40% of GSSG equivalents lost. Because portal elevations of GSH and CySSG were not inhibited by AT125, they were formed by a gamma-GT-independent mechanism(s). Given that cysteine was present in the mesenteric vasculature, the most likely mechanism to explain GSH and CySSG formation was via nonenzymatic thiol-disulfide exchange between GSSG and cysteine. Uptake of vascular GSSG by pancreas, small intestine (jejunum and ileum), or colon apparently did not occur as tissue contents of GSSG or GSH were not elevated, except for a small elevation of GSH in pancreas when mesenteric gamma-GT was inhibited with AT125. Additionally, GSSG was not transported from mesenteric vasculature into the small intestinal lumen because luminal levels of GSSG or GSH were not elevated. Further, total cysteine equivalents in lumen were unchanged indicating that GSSG was not transported to lumen and degraded to cystine by gamma-GT and dipeptidases localized to the intestinal brush-border. These results indicate that GSSG present in mesenteric vasculature is metabolized in the vascular compartment by gamma-GT-dependent and independent reactions; together, these account for over 80% of lost GSSG equivalents. They also suggest that organs of the mesentery may play a quantitatively important role in plasma GSSG clearance and modulation of vascular thiol-disulfide balance. PMID- 7992318 TI - Inhibition of intercellular communication by 2,3,7,8-tetrachlorodibenzo-p-dioxin and dioxin-like PCBs in mouse hepatoma cells (Hepa1c1c7): involvement of the Ah receptor. AB - The effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (2,3,7,8-TCDD) and the coplanar 3,3',4,4'-tetrachlorobiphenyl (3,3',4,4'-TCB) and 3,3',4,4',5,5' hexachlorobiphenyl (3,3',4,4',5,5'-HCB) on intercellular communication (IC) were determined in order to investigate the in vitro tumor promoting potency of these compounds. 2,3,7,8-TCDD and the two coplanar PCBs tested caused a rapid (2 hr) and a sustained inhibition (48 hr) of IC in the mouse hepatoma cell line (Hepa1c1c7) to 20 and 50% of the unexposed control, respectively. Inhibition of IC was dose dependent with an EC50 range of about 50-100 pM for 2,3,7,8-TCDD, 2-5 nM for 3,3',4,4'-TCB, and 10-15 nM for 3,3',4,4',5,5'-HCB, respectively. A comparison of the IC inhibitory effects of 2,3,7,8-TCDD and PCBs with a well known aryl hydrocarbon receptor (AhR)-mediated response, the induction of ethoxyresorufin O-deethylase (EROD) activity, in the same cells revealed EROD induction by 2,3,7,8-TCDD, 3,3',4,4'-TCB, and 3,3',4,4',5,5'-HCB with EC50 ranges of 100-200 pM, 20-70 nM, and 5-10 nM, respectively. The time course of IC inhibition was paralleled by EROD induction, although the time of onset of the response was earlier for IC (1 hr) than for EROD (2.5 hr). A role of the AhR in the inhibition of IC by 2,3,7,8-TCDD and PCBs was demonstrated by the lack of inhibition in AhR-defective Hepa1c1c7 cells. Transient inhibition of IC was observed in the mutant cells only at early time points (within 2 hr of exposure). These results and the observation that alpha-naphtoflavone (an AhR antagonist) greatly reduced the 2,3,7,8-TCDD-dependent sustained inhibition of IC strongly support a role of the AhR in the sustained inhibition of IC by these compounds. Furthermore, these data suggest that the mouse Hepa1c1c7 cells may be a good model in which to study in vitro tumor promoting capacity of dioxins, PCBs, and related compounds. PMID- 7992319 TI - Immunohistochemical localization of CYP1A and CYP3A-like isozymes in hepatic and extrahepatic tissues of Atlantic cod (Gadus morhua L.), a marine fish. AB - The cellular localization of inducible CYP1A and constitutive CYP3A-like forms in different organ systems of Atlantic cod (Gadus morhua) was determined in control fish and fish exposed to beta-naphthoflavone (BNF). Paraffin-embedded sections were stained with polyclonal rabbit anti-cod P450 1A IgG or rabbit anti-rainbow trout P450con (a putative CYP3A form which cross-reacts with purified cod P450b) serum by the avidin-biotin peroxidase complex method. Following BNF-exposure of cod, CYP1A induction was immunohistochemically demonstrated in hepatocytes and endothelial cells of liver, the endocardium and vascular endothelium in the atrium and ventricle, and epithelial cells of the proximal tubular segment, endothelial cells, and interrenal cells in kidney. The vascular endothelium was the main site of induction of CYP1A in gills, spleen, gut, pyloric caecae, and gonads. The CYP3A-like isozyme P450b was mainly localized to hepatocytes, renal tubular epithelium, and epithelial cells of the mucosa in the intestine. Furthermore, the distribution of P450b was not affected by BNF exposure. The localization of P450b bears interesting similarities to the localization of CYP3A in mammals supporting the CYP3A-like identity of cod P450b. Simultaneous localization of inducible CYP1A and a constitutively expressed CYP isoenzyme has not previously been reported in fish. This is also the first presentation of cellular distribution of a CYP3-like isozyme in fish. Staining of CYP1A in endothelial cells supports previous observations that endothelium is a major site of CYP1A induction following xenobiotic exposure in fish. The observation of CYP1A induction in interrenal cells has important implications for possible endocrine effects of xenobiotic exposure. PMID- 7992320 TI - Dapsone-induced hematologic toxicity: comparison of the methemoglobin-forming ability of hydroxylamine metabolites of dapsone in rat and human blood. AB - The relative methemoglobin (MetHgb) forming ability of two metabolites of dapsone, dapsone hydroxylamine (DDS-NOH) and monoacetyldapsone hydroxylamine (MADDS-NOH), were compared in rat and human whole blood. Concentration-response curves for the two metabolites were generated in vitro in whole blood. Data were fit to both the Emax and Sigmoid Emax models. The Emax values for MetHgb formation in rat blood for MADDS-NOH and DDS-NOH fitted to the Emax model were 83 (8) and 84 (2)%, while the EC50 values were 1087 (283) and 828 (104) microM, respectively (mean +/- SD). Neither these values nor those generated for the Sigmoid Emax model differed significantly between the two metabolites. Similarly, the Emax values in human blood for MADDS-NOH and DDS-NOH fitted to the Emax model were 79 (5) and 80 (2)%, while the EC50 values were 90 (17) and 95 (19) microM, respectively. These values also did not differ between the two metabolites using either pharmacodynamic model. MetHgb was produced at the same rate, reached similar peak concentrations, and exhibited the same rate of decline with both metabolites. The area under the MetHgb content versus time curve did not differ between the two metabolites. These data demonstrate that MADDS-NOH and DDS-NOH are equipotent and equally efficacious in their MetHgb-forming ability. Investigation of the disposition of these metabolites is necessary to assess their relative role in dapsone-induced toxicity in vivo. PMID- 7992321 TI - Past and present trends of community health in tropical countries. PMID- 7992322 TI - Progress in the control of schistosomiasis in Mauritius. AB - Schistosomiasis in Mauritius was mainly dealt with in hospitals and their annexed services until 1988 when a special control programme was started by the Ministry of Health with the technical help of the World Health Organization and the financial assistance of the Theodor Bilharz Foundation (Germany). As only Schistosoma haematobium is present in Mauritius, this consisted of screening for microhaematuria and/or eggs in urine, health education and mollusciciding. All the primary school population, some of the secondary school population, and most of the general population in the foci of infection in the 3 endemic districts of Pamplemousses, Port Louis and Grand Port were screened. There has been a marked reduction in the prevalence of schistosomiasis in the island. In the school population aged 5-11 years, prevalence fell from 0-8.2% in 1988 and 1989 to zero in all the schools surveyed since 1991. The prevalence in the general population fell from an average of 6.6% in 1988 to 0.9% in 1992. PMID- 7992323 TI - A successful control programme for lymphatic filariasis in Hubei, China. AB - This paper describes the epidemiology and control of human lymphatic filariasis in Hubei province, China from the 1950s to the 1990s. Brugia malayi, transmitted by Anopheles sinensis, and Wuchereria bancrofti, transmitted by Culex quinquefasciatus, were found in 69 of 78 counties and cities. The distribution of filaria species was distinct, with B. malayi endemic in the plains, mixed infections in hilly areas, and W. bancrofti in the mountains. Before 1979, the microfilaria rate (mfr) in some villages was as high as 30.69%. Since 1979, large scale control programmes have been carried out and 27,875,267 blood examinations have been made. Up to 1988, the mfr in all endemic villages decreased to below 1%. From 1989 to 1991 about 200,000 people had their blood examined yearly and few cases were detected. The continued use of mass blood examination for filariasis surveillance is not economic at such low levels of infection, and it is suggested that selective treatment of microfilaremic persons should be the main control measure at this stage. PMID- 7992324 TI - Testing a participatory strategy to change hygiene behaviour: face washing in central Tanzania. AB - A participatory strategy to increase face washing was designed and tested in central Tanzania. Changing children's face-washing behaviour is postulated to be important in preventing the transmission of eye disease, particularly blinding trachoma. The strategy used non-formal adult education techniques at neighbourhood level meetings to build a community consensus to keep children's faces clean for the prevention of eye disease. Men, women, schoolchildren, traditional healers and village social groups participated in the intervention. The strategy was evaluated by observing changes in numbers of clean faces of a sample of preschool children in the village. Clean faces increased from 9% to 33% over the course of a year. Factors which were related to sustained change in children's clean faces included distance to water, age of the child, and presence of a corrugated metal roof. Owning cattle was associated with lack of sustainable change in this population. PMID- 7992325 TI - The isolation of Leishmania major from Phlebotomus (Paraphlebotomus) caucasicus, in Isfahan province, Islamic Republic of Iran. AB - As part of a general survey of leishmaniasis and sandflies in the focus of zoonotic cutaneous leishmaniasis (ZCL) at Borkhar, a rural district north of the city of Isfahan, central Iran, Phlebotomus (Paraphlebotomus) caucasicus Marzinowsky from gerbil and jird burrows were found naturally infected with Leishmania major, zymodeme MON-26 (= LON-1). This is the first characterized isolate of L. major from a sandfly vector in Iran. PMID- 7992326 TI - The interpretation of intensity and aggregation data for infections of Schistosoma haematobium. AB - The relationships between mean intensities of infection, the aggregation of infection among hosts, and host age are analysed using data from 2 large (> 3000 individuals) field studies of Schistosoma haematobium infection. The data show a convex relationship between mean intensity and age, a convex relationship between an inverse index of aggregation and age, and an age-dependent relationship between the mean and aggregation of infection intensity when levels of infection are high. These patterns are qualitatively compared with the output of mathematical models based on an immigration-death process (model I), and incorporating age-dependent changes in the distribution of exposure to infection as suggested by field data (model II), or reductions in the rate of infection as a function of either current (model III) or cumulative (model IV) parasite burdens, that is, density-dependent processes without or with memory, respectively. Models II and III were able to reproduce observed patterns, but model IV, which is a possible representation of acquired immunity, was not. These results are consistent with the following assumptions: (i) age-related patterns of aggregation can be generated without recourse to density-dependent processes; (ii) the epidemiological impact of density-dependent processes depends on whether these act with or without memory; and (iii) any acquired immunity to human S. haematobium infection may be significantly less than life-long. PMID- 7992328 TI - Epidemiology of human toxocariasis in La Reunion. AB - In La Reunion island (Indian Ocean) a seroepidemiological survey for toxocariasis was carried out among 387 subjects over 15 years old by Western blotting using Toxocara canis excretory-secretory larval antigens; 92.8% of the sera were positive. Statistical study, including logistic regression analysis, showed a significant correlation of Western blot results with sex, age, and absence of water supply. The final logistic model demonstrated that only the last 2 factors were significant multiplicative risk factors for toxocariasis. Sex was an independent risk factor. With this level of infection, we suggest that further surveys of ocular toxocariasis in children and teenagers of La Reunion would be advisable. PMID- 7992327 TI - Strongyloides stercoralis in an urban slum community in Bangladesh: factors independently associated with infection. AB - Stool samples from 880 residents in an urban slum in Dhaka, Bangladesh, were collected on 3 occasions over one year, and examined for intestinal parasites. Information on many potential risk factors for infection was obtained by questionnaire from a respondent in each household studied. In a crude univariate analysis of the data, several of the factors were found to be significantly associated with Strongyloides stercoralis infection. Most of these factors were co-variate with one another, and with poverty generally. Using Mantel-Haenszel chi 2 tests to control for confounding effects of each variable individually, the following 4 factors remained independently associated with S. stercoralis infection: respondent's use of a community latrine rather than a private latrine, living in a house with an earth floor rather than a cement floor, being of Bihari ethnicity, and being 7-10 years of age. Implications of these results for the epidemiology and control of strongyloidiasis are briefly discussed. PMID- 7992329 TI - Hepatitis B and C in Juba, southern Sudan: results of a serosurvey. AB - To compare the epidemiology of hepatitis B virus (HBV) with hepatitis C virus (HCV) in a southern Sudanese population, 666 out-patients attending 6 public clinics in the city of Juba were enrolled in a serosurvey. The average age of subjects was 16 years; 54% were female. Of the 651 samples tested for hepatitis B markers, HBsAg was found in 26% and anti-HBc in 67%. In contrast, only 21 (3%) of the 666 samples were positive for anti-HCV using a second generation immunoblot assay (RIBA-2). Seventeen (81%) of the 21 anti-HCV-positive subjects were positive for anti-HBc, compared to 66% (418/630) of subjects negative for anti HCV (P = 0.07). None of the anti-HCV-positive subjects reported receiving a prior blood transfusion and only 5 subjects reported a history of jaundice. Nine of the 21 (43%) anti-HCV-positive subjects reported a history of scarification, compared to 23% (148/645) of anti-HCV-negative subjects (P = 0.01). Hepatitis B infection was also associated with scarification by univariate analysis. However, after adjustment for age a history of scarification was not significantly associated with hepatitis C infection, but it was with HBV infection (odds ratio = 1.5, 95% CI 1.0-2.5; P = 0.05). The findings of this study indicate that HCV infection is not highly endemic in this population and that the epidemiology of HCV differs from that of HBV. PMID- 7992330 TI - Hepatitis C virus antibodies in prostitutes in Niger. PMID- 7992331 TI - Malaria: how useful are clinical criteria for improving the diagnosis in a highly endemic area? AB - To assess the validity of clinical criteria, we investigated 2096 outpatients diagnosed as malaria cases by nurses at a rural health subcentre in a highly endemic area of Papua New Guinea. 73% of the children < 10 years old had a positive blood slide for any species of Plasmodium and 32% had > or = 10,000 P. falciparum parasites per microL. For adults the frequencies were 51% and 9%, respectively. Stepwise logistic regression identified spleen size, no cough, temperature, no chest indrawing, and normal stools as significant predictors for a positive blood slide in children; no cough and normal stools predicted a positive blood slide in adults. Fever, no cough, vomiting, and enlarged spleen were significant predictors for a P. falciparum parasitaemia > or = 10,000/microL in children; in adults the only predictor was vomiting. In children the association of no cough and enlarged spleen had the best predictive value for a positive blood slide, and a temperature > or = 38 degrees C had the best predictive value for a P. falciparum parasitaemia > or = 10,000 microL. In adults, no major symptom had a good predictive value for a positive blood slide but vomiting had the best predictive value for a P. falciparum parasitaemia > or = 10,000/microL. When microscopy is not available, these findings can help in areas of high endemicity to determine which patients with a history of fever are most likely to have malaria and, more importantly, for which patients another diagnosis should be strongly considered. PMID- 7992332 TI - The effect of BCG vaccination on the leishmanin skin test. PMID- 7992333 TI - Serodiagnosis of Asian leishmaniasis with a recombinant antigen from the repetitive domain of a Leishmania kinesin. AB - rK39 is a recombinant product of the 39 amino acid repeats found in a kinesin like gene of visceral Leishmania spp. This and other antigens were compared for immunodiagnostic potential by enzyme-linked immunosorbent assay with sera from confirmed cases of Asian cutaneous and visceral leishmaniasis. In preliminary trials, rK39 proved superior to 2 purified Leishmania antigens, a cytosolic protein (p36) and a membrane protein (gp63), for immunodiagnosis of visceral leishmaniasis. Of the 53 visceral cases from China and Pakistan assayed, 52 were seropositive (98%) at a 10(-1) dilution with 36 ng of rK39. End point titrations of 27 highly positive samples yielded anti-rK39 antibody titres ranging from c. 10(-3) to beyond 10(-4). Antigen titrations with one positive serum further revealed that rK39 was 25-fold more sensitive than Leishmania whole cell soluble lysates. 31 cutaneous leishmaniasis cases from Turkey assayed for anti-rK39 antibody gave reactions ranging from negative or marginally positive to positive. In Brazil, all cutaneous and mucocutaneous leishmaniasis cases gave negative results in this assay. PMID- 7992334 TI - Detection of immune complexes in tissues of persons infected with Entamoeba histolytica. AB - Immune complexes were detected by radioimmunoassay in colonic tissue from 71 to 122 patients (58%) excreting Entamoeba histolytica cysts and in liver tissue from 5 of 16 of these patients. Complexes were also found in colonic tissue from 9 of 56 other patients (16%) who were not excreting cysts. PMID- 7992335 TI - In-hospital morbidity and mortality due to malaria-associated severe anaemia in two areas of Malawi with different patterns of malaria infection. AB - We examined the relative contribution of malaria-associated severe anaemia (parasitaemia and haematocrit < or = 15%) to malaria-related morbidity and mortality among children admitted at 2 hospitals in areas with different seasonal patterns of malaria infection in Malawi. The prevalence of malaria-associated severe anaemia was 8.5% among admissions at the hospital in an area with sustained, year-round infection (Mangochi District Hospital [MDH]), compared to 5.2% at the hospital in an area with a fluctuating pattern of infection (Queen Elizabeth Central Hospital [QECH]). Infants at MDH were nearly twice as likely to have malaria-associated severe anaemia as were those at QECH. Parasite density on admission was not related to the risk of severe anaemia at MDH, but it was at QECH. A similar proportion of all deaths was attributed to malaria at MDH (17.5%) and QECH (20.4%). However, malaria-associated severe anaemia accounted for 54% of malaria-related deaths at MDH compared to only 32% at QECH. Malaria-associated severe anaemia contributed significantly to morbidity and mortality at both sites, but its impact was more marked in the area with a sustained pattern of infection. These findings suggest that seasonal fluctuations in malaria infection may contribute to differences in patterns of malaria disease. PMID- 7992336 TI - Sporotrichoid cutaneous leishmaniasis due to Leishmania major of different zymodemes in the Sudan and Saudi Arabia: a comparative study. AB - Sporotrichoid cutaneous leishmaniasis is due to dissemination of amastigotes via the lymphatics to the subcutaneous tissues. A comparison was made between the potential to disseminate by this route of 2 parasites of different zymodemes in Sudan and Saudi Arabia. In Sudan cutaneous leishmaniasis is caused by Leishmania major zymodeme LON-1, and in Saudi Arabia by L. major LON-4. Sporotrichoid leishmaniasis was significantly more common in Sudan, occurring in 23% of patients compared with 10% in Saudi Arabia. Lymph node involvement was slightly more prevalent in the Sudan. Clinical and pathological differences between subcutaneous nodules, particularly when they ulcerate, and multiple primary cutaneous lesions are described and treatment of localized and sporotrichoid leishmaniasis is discussed. The pathological features of the primary lesions in the Sudan and Saudi Arabia were similar. PMID- 7992337 TI - Parasitological and clinical aspects of bancroftian filariasis in Kassena-Nankana District, upper east region, Ghana. AB - A survey of the prevalence of bancroftian filariasis was conducted in August September 1992 in the northern part of the Kassena-Nankana District, Upper East Region, Ghana. 200 compounds from 3 different communities were randomly selected from the vitamin A trial database. All resident compound members were examined for clinical manifestations of lymphatic filariasis and capillary blood was obtained between 21:00 and 01:00 and examined using the counting chamber technique. 1603 people were examined, 741 males and 862 females. The overall prevalence of microfilaraemia was 32.4% (95% confidence interval 30.1-34.7). Geometric mean microfilaria density (infected persons only) was 794 per mL. The most important clinical manifestation was hydrocele (in 32% of males) followed by limb elephantiasis (in 3.6% of the study population). There was no significant difference between the 3 communities in clinical or parasitological findings. PMID- 7992338 TI - Ultrasonographic evidence for stability of adult worm location in bancroftian filariasis. PMID- 7992339 TI - Long-term disability due to guinea worm disease. AB - The village-based surveillance system for guinea worm disease (dracunculiasis), which has been established in all endemic villages in Ghana, was used to carry out a retrospective study of long-term disability due to the disease. A sample of 195 cases was interviewed and examined, 12-18 months after emergence of the worm. Currently continuing pain when walking or working, attributable by its location and date of onset to the episode of dracunculiasis, was reported by 55 persons (28.2%). Some difficulty in performing at least one of 6 everyday physical activities, attributable after careful interview to the episode, was reported by 66 respondents (34.0%), of whom 10 (5.1%) were unable to carry out one of the activities. In one case, the disease had caused impairment of movement of the joints of the right thumb. The prevalence of serious permanent physical impairment among the cases in the study was thus 0.5%. PMID- 7992340 TI - Opisthorchis viverrini infection in Thailand: symptoms and signs of infection--a population-based study. AB - A population-based study of the clinical, laboratory and ultrasonographic findings in patients suffering from mild or moderate opisthorchiasis in Prachinburi province, Thailand was conducted in 1990-1992. The effectiveness of treatment with praziquantel at 40 mg/kg body weight was evaluated. After treatment, a long-lasting, marked improvement in the well-being of the study group was observed. Symptoms common in opisthorchiasis infection decreased in intensity and the clinical response showed total or partial remission in 98% of all cases studied. Total and direct bilirubin concentrations decreased significantly and remained low up to the end of the follow-up period of 2 years, indicating a reduction in cholestasis. Also, white blood cell counts decreased initially, which can be interpreted as a reduction in inflammation intensity. No relationship was found between intensity of infection and age or clinical findings. Population-based treatment of opisthorchiasis appears to have had a significant impact on public health in north-east Thailand. However, it is also evident that drug therapy alone will not solve the opisthorchiasis problem, as indicated by the reinfection rate of almost 10% at the end of the study. PMID- 7992341 TI - Ataxia in patients infected with Salmonella typhi phage type D2: clinical, biochemical and immunohistochemical studies. AB - Reversible cerebellar dysfunction has been described in association with typhoid fever by a number of authors. Ataxia and tremors are relatively common manifestations of typhoid fever in Papua New Guinea. A series of 14 patients with typhoid fever and ataxia was compared with non-ataxic typhoid patients. Hyponatraemia and hypoalbuminaemia were common in both groups and more severe in the ataxic group. Hypotension was also more common in the ataxic group. These features may reflect more severe disease. All isolates of Salmonella typhi, from both ataxic and non-ataxic patients, were phage type D2 which is endemic around Port Moresby. Tests for autoantibodies cross-reacting with cerebellar tissue were negative. It is possible that cerebellar dysfunction in typhoid fever is more common in association with phage type D2. PMID- 7992342 TI - Low incidence of clinically significant gastroduodenal pathology despite a high incidence of Helicobacter pylori infection. AB - Gastric Helicobacter pylori infection is common throughout the tropics yet does not always correlate with the incidence of serious upper gastrointestinal pathology. In a consecutive series of 213 patients examined by gastroscopy for dyspepsia in northern Nigeria, 176 (92%) of 193 with acceptable biopsies had gastritis. Only 16 (8%) had a histologically normal gastric mucosa. H. pylori was present in 161 of 192 patients (84%); 31/41 (75%) with chronic gastritis and 130/135 (96%) with active gastritis. Serious pathology, ulcer and gastric cancer were present in only 29 (14%). PMID- 7992343 TI - Analysis of referral letters to assess the management of poisonous snake bite in rural Papua New Guinea. AB - A prospective series of patients envenomed after snake bite was seen at Port Moresby General Hospital (PMGH), Papua New Guinea, between January 1991 and December 1992. Referral letters were received with 60 of the patients who had been initially seen at a health centre. These letters were analysed in conjunction with our own clinical observations. The importance of non-clotting blood and local lymphadenopathy as early signs of systemic poisoning did not appear to be universally recognized by staff in health centres. In some cases, no attempt was made to transfer the patient to hospital until signs of neurotoxicity were established with potentially dangerous delay. Analysis of both hospital and health centre records suggests that the majority of deaths which occurred in Central Province, Papua New Guinea, during the period of the study were due to delay in transfer to hospital. We suggest that all patients with unequivocal signs of envenoming in Central Province, Papua New Guinea, should be transferred to PMGH as soon as possible. Antivenom should also be given as soon as possible, but this does not remove the need for immediate transfer. PMID- 7992344 TI - Early childhood feeding practices in northern Cameroon. AB - Following the identification of differences in disease patterns among infants from households of different social groups (Moslem and non-Moslem) in northern Cameroon, 534 mothers and their children 0-23 months old were studied to determine early childhood feeding practices in the 2 groups. Several significant differences were revealed. Compared with non-Moslem infants, Moslems were more likely to be given animal milk instead of breast milk before the age of 3 d. On average, millet pap was introduced to Moslem babies between their 1st and 2nd months and to non-Moslem babies between their 3rd and 4th months. Moslem mothers more commonly prepared pap with oil or cow butter as an ingredient. Moslem mothers also planned to wean their children at an earlier age than non-Moslems and were less likely to report boiling their children's drinking water. Moslem mothers of infants less than 5 months old were likely to believe their breast milk was insufficient. The implications of these findings on the higher incidence of infant diarrhoea, stunting and early childhood death among Moslems are discussed. PMID- 7992345 TI - Towards optimal regimens of parenteral quinine for young African children with cerebral malaria: unbound quinine concentrations following a simple loading dose regimen. AB - Nine children with severe falciparum malaria were treated with an intravenous quinine regimen which did not require burettes or infusion pumps, to determine its practicability and to ensure that therapeutic drug concentrations were achieved and maintained throughout the dose interval. The regimen comprised quinine dihydrochloride (15 mg/kg; 12.5 mg/kg of the free base), which was added to a bag of intravenous fluid (after wastage of all but 100 mL), and given via standard giving sets over 2 h. Blood was drawn sequentially during the infusion, and for 12 h thereafter; plasma water was obtained by ultrafiltration of samples at the bedside, and quinine concentration was measured, in plasma and plasma water, by high performance liquid chromatography. Drug administration was practicable without burettes or infusion pumps; unbound drug concentrations exceeded the 99% inhibitory concentration for local parasites within 0.5 h, and remained within the therapeutic range for the entire dose interval. This loading dose regimen can now be recommended for young children in African hospitals; maintenance doses of 10 mg/kg should be given at 12 h intervals until oral antimalarial drugs are possible. These recommendations will need to be modified if susceptibility to quinine declines. PMID- 7992346 TI - Praziquantel for the treatment of Diphyllobothrium nihonkaiense infections in humans. PMID- 7992347 TI - The impact of five years of annual ivermectin treatment on skin microfilarial loads in the onchocerciasis focus of Asubende, Ghana. AB - Following the registration of ivermectin (Mectizan) for human use in the treatment of onchocerciasis, in 1987 the Onchocerciasis Control Programme in West Africa (OCP) begun a series of trials in order to determine the safety of the drug when used on a large scale and its potential for morbidity control. This paper reports the changes in skin microfilarial loads during the first 5 years of annual treatment in the holoendemic focus of Asubende in Ghana, which was the largest trial area and which also had the longest series of follow-up surveys. The general observed pattern was a marked reduction of microfilarial loads shortly after each treatment followed by a steady repopulation of the skin until a subsequent treatment round. The overall reduction of microfilarial loads observed between the base line survey and one year after the last treatment was 90% for the total population examined and over 93% for a cohort which received the drug at all 5 treatment rounds. In contrast, there was only a very gradual decrease in the prevalence of infection in the population after subsequent treatments. The study further emphasizes that even a single treatment with ivermectin has a significant medium-term impact on microfilarial loads. Microfilarial counts barely increased after 14-16 months of treatment and stabilized around 55% of pre-treatment counts 2-4 years after a single treatment. PMID- 7992348 TI - A randomized controlled trial comparing mebendazole and albendazole against Ascaris, Trichuris and hookworm infections. AB - The efficacies and side effects of single dose treatments with 500 mg mebendazole (Janssen Pharmaceutica) and 400 mg albendazole (SmithKline Beecham) against intestinal nematodes were compared in a single-blind, randomized controlled trial among 2294 children aged 6 to 12 years on Pemba Island, Zanzibar, among whom infections with Ascaris, hookworms and Trichuris were highly prevalent. Both drugs were highly effective against Ascaris, with cure rates of over 97%. The cure rates for Trichuris were low, but mebendazole was significantly better than albendazole and produced a greater reduction in the geometric mean egg count. Mebendazole was inferior to albendazole in curing hookworm infections and in reducing the geometric mean egg count. There was no difference in the frequency of side effects reported by heavily infected children treated with either drug. In a trial on 402 children, 500 mg mebendazole (Janssen) was compared with a generic version of the drug, 500 mg mebendazole (Pharmamed). No difference was apparent in the efficacies of the 2 treatments against any of the 3 parasites studied. PMID- 7992349 TI - The effects of iron supplementation during pregnancy, given by traditional birth attendants, on the prevalence of anaemia and malaria. AB - A randomized, double-blind, placebo-controlled community-based trial of oral iron supplementation (200 mg ferrous sulphate daily) administered to multigravid pregnant women by traditional birth attendants (TBAs) was carried out in a rural area of The Gambia. Iron supplementation led to a significant reduction in the prevalence of anaemia and of iron deficiency. Iron supplementation was not accompanied by increased susceptibility to malaria infection; there was no difference in the prevalence and severity of peripheral blood or placental malaria infection between the 2 groups of women. The birth weight of children born to women who received iron prophylaxis was increased by an average of 56 g. It is concluded that oral iron prophylaxis can be successfully delivered through TBAs integrated into a primary health care programme. This simple intervention can produce significant beneficial effects on the health of the mother without inducing increased susceptibility to malaria and has the potential for reducing perinatal mortality by increasing birth weight. PMID- 7992350 TI - Management of protein-energy malnutrition in Nigeria: an evaluation of the regimen at the Kersey Nutrition Rehabilitation Centre, Nigeria. AB - An evaluation of the performance of the Kersey Nutrition Rehabilitation Centre in Nigeria was undertaken with particular focus on mortality, rate of weight gain, and the management strategy. During 1987-1991 the total number of admissions for protein-energy malnutrition (PEM) was 803. The age group most commonly represented were those aged 12-29 months. Kwashiorkor cases formed the largest proportion of admissions (66%). Marasmic cases consistently predominated among children aged < 18 months. Average mortality was 22% during the 5 years. Mortality among oedematous patients was 25% compared with 15% among marasmic cases. The rate of weight gain averaged 7 g/kg/d for marasmic and marasmic kwashiorkor cases and 6 g/kg/d for kwashiorkor cases. Specific recommendations are made to improve case-management, focusing particularly on the prevention of deaths in the first few days after admission. PMID- 7992351 TI - A beta 1 integrin-like molecule in Entamoeba histolytica. AB - Human invasive amoebiasis is highly destructive, causing rapid necrosis and liquefaction of all tissues reached by the trophozoites. Degradation of extracellular matrix components (EMC) has been demonstrated during invasion of the basal lamina. Pursuing the idea that trophozoites might behave similarly to other invasive cells with respect to their interaction with EMC, plasma membrane proteins biochemically or functionally related to integrins were looked for. A 140 kDa molecular mass membrane protein from Entamoeba histolytica trophozoites with the characteristics of a beta 1 integrin-like fibronectin receptor was identified. PMID- 7992352 TI - Enzyme polymorphisms in Ascaris lumbricoides in Bangladesh. AB - Fourteen enzymes of Ascaris lumbricoides were analysed electrophoretically on cellulose acetate plates; 8 stained well and 3 were found to be polymorphic. Allelic and genotypic frequencies at the 3 polymorphic enzyme loci, Mpi, Pgi and 6-Pgd, were determined in a sample of 117 worms from 8 children living in different houses in an urban slum in Bangladesh. Allele frequencies in samples of parasites from the different children were compared to test for the possibility of non-random distribution of parasite genotypes between people. No strong evidence of differences was found. Diploid genotype frequencies did not deviate significantly from those expected from the Hardy-Weinberg equilibrium. Significant linkage disequilibrium was observed in one of 3 pairs of enzyme loci tested, which might suggest that some genetic subdivision exists in the local A. lumbricoides population, although no strong interference should be made from this single result. Overall, the results suggest that the worms sampled formed part of a single population which appears to be randomly mating. PMID- 7992353 TI - The impact of gender on renal transplantation. PMID- 7992354 TI - Effects of rapamycin on renal hemodynamics, water and sodium excretion, and plasma levels of angiotensin II, aldosterone, atrial natriuretic peptide, and vasopressin in pigs. AB - We have investigated the acute effects of rapamycin on renal hemodynamics, water, sodium and lithium excretion rates, and plasma levels of angiotensin II, aldosterone, atrial natriuretic peptide and vasopressin in 34 Lancaster/Yorkshire female pigs, a breed that has a renal structure/function resembling that of the human kidney. Three different dosages were given over a 1-hr period: dose A, 0.1 mg/kg (n = 8); dose B, 0.2 mg/kg (n = 8); dose C, 0.4 mg/kg (n = 8); and P, placebo vehicle (n = 10). Glomerular filtration rate (GFR) and renal plasma flow (RPF) were measured by constant infusion clearance technique using 125I iothalamate and 131I-hippuran, and hormonal parameters were measured by RIA. Renal hemodynamics, water and sodium excretion rates, and tubular function, evaluated by the lithium clearance technique, were unchanged both during and up to 2 hr after rapamycin infusion, although GFR and RPF increased when rapamycin was given in supratherapeutic dosages of 0.4 mg/kg (GFR: P, 4.4%; A, 7.9%; B, 2.5%; C, 13.3% [P < 0.05]; RPF: P, 7.1%; A, 4.9%; B, 3.9%; C, 15.3% [P < 0.01], median values). It is concluded that infusion of rapamycin has no acute deleterious effects on renal function in pigs in therapeutic to supratherapeutic dosages. PMID- 7992355 TI - The early release of interleukin-2, tumor necrosis factor-alpha and interferon gamma after ischemia reperfusion injury in the lung allograft. AB - A period of cold and warm ischemia is obligatory when performing lung transplantation. Subtle ischemia-reperfusion injury induced in the course of transplantation can pass undetected or cause a short phase of reversible lung dysfunction. We hypothesized that ischemia-reperfusion injury may result in the local release of cytokines that have the capability to mediate acute lung injury early following transplantation. To test this hypothesis, 10 mongrel dogs were subjected to left lung allotransplantation. As performed in the clinical setting, donor lungs were preserved with Eurocollins solution and stored at 4 degrees C for 4 hr, which was followed by 1 hr of warm ischemia. Recipients received standard immunosuppression of cyclosporine, azathioprine, and low dose steroids. Bronchoalveolar lavage (BAL) and open lung biopsies were performed before operation and at approximately 1 hr, 4 hr, 24 hr, and 1 week after transplantation. A significant increase in BAL IL-2 levels was observed 4 hr after surgery (0 hr: 349 +/- 138 pg/ml; 4 hr: 757 +/- 284 pg/ml) (mean +/- SEM) (P < 0.05) which subsequently decreased 24 hr (320 +/- 168 pg/ml) after transplantation. BAL TNF-alpha levels were significantly increased 1 hr after transplantation (P < 0.05) (0 hr: 3.4 +/- 0.65 pg/ml; 1 hr: 13.3 +/- 8.0 pg/ml) returning to baseline after 24 hr (5.8 +/- 2.8 pg/ml). BAL IFN-gamma levels also significantly increased 1 and 4 hr after transplantation (0 hr: 7.2 +/- 2.1 pg/ml; 1 hr: 68.2 +/- 49.2 pg/ml; 4 hr: 301 +/- 131 pg/ml) (P < 0.05). This decreased back to baseline after 24 hr and 1 week (5.2 +/- 1.2 pg/ml and 9.7 +/- 7.9 pg/ml, respectively). There were no changes detected in plasma levels of cytokines. Histology showed evidence of grade 1-2 rejection after 1 week. We conclude that subjection of a lung allograft to standard periods of cold-warm ischemia will result in a temporary early elevation of IL-2, TNF-alpha, and IFN gamma detectable only in the bronchoalveolar compartment. Such local increase in cytokines in the lung allograft may play an important role in the development of early allograft dysfunction. PMID- 7992356 TI - Mechanisms of injury in porcine livers perfused with blood of patients with fulminant hepatic failure. AB - Hyperacute rejection of renal and cardiac xenografts is initiated by the reaction of recipient natural antibodies and complement with endothelial cell antigens of the donor organ. The liver is thought to be less susceptible to this form of rejection; however, the mechanisms underlying its decreased susceptibility are not known. We investigated the organ injury occurring in porcine livers perfused with blood from 4 human subjects with fulminant hepatic failure. Nine porcine livers were perfused via an extracorporeal circuit in order to provide temporary metabolic support. Each porcine liver exhibited metabolic function, and the duration of xenoperfusion ranged from 2 to 5 hr. Histologic examination of the xenoperfused livers revealed focal hepatocellular necrosis, prominent infiltration of neutrophils, and, in 7 of 9 cases, periportal and centrilobular hemorrhage and thrombosis. Immunopathology demonstrated minimal or no human IgM and IgG along the small vessels and sinusoidal surfaces. Trace deposits of human IgM were observed along the luminal surfaces of large blood vessels in most cases. Trace deposits of C3 were noted in 2 of 9 livers; however, C4, iC3b, C5b, properdin, and the membrane attack complex were not detected. Human anti-porcine natural antibody titers decreased less than expected during the perfusions. Serum CH50, C3, and C4 levels were low before each procedure and decreased slightly with perfusion. One patient perfused 2 porcine livers and a human liver. The human liver had focal hepatocellular necrosis, trace deposits of IgM, no deposits of complement, and an infiltrate consisting of neutrophils; however, the neutrophil influx was less than that observed in the xenoperfused livers. To further evaluate the effects of alloperfusion, venovenous bypass was established in 2 pigs and the extracorporeal circuit was utilized to perfuse 2 porcine livers. The alloperfused porcine livers had focal hepatocellular necrosis and a minimal infiltrate of neutrophils. There were no deposits of porcine IgM, IgG, or complement components. In conclusion, although the porcine livers perfused by human blood sustained structural damage, the time course, the absence of immune deposits, and the findings of similar, albeit less severe, lesions in the alloperfused livers suggest that the pathogenesis of tissue injury in the xenoperfused livers differs from that of hyperacute rejection and may be related to the action of recipient neutrophils. PMID- 7992357 TI - Radioisotopic evaluation of renal function in cyclosporine-treated pediatric and adult renal transplant recipients and their living donors. A study of 152 donor recipient pairs. AB - Renal function was studied in 2 groups of renal transplant recipients and their donors by technetium-99m diethylenetriamine pentaacetic acid and a gamma camera. The pediatric group (group A) comprised 40 children and their adult kidney donors. The adult group (group B) consisted of 112 consecutive adult renal transplant recipients and their adult donors. All patients received kidneys from living donors and were given the same immunosuppression protocol (PRED plus CSA). Donor glomerular filtration rate (GFR) was determined before nephrectomy and at a mean period of 30 (range 10-50) months after nephrectomy. The graft GFR was measured at 1, 3, 6, and 12 months and at the most recent follow-up visit. Moreover, the functional reserve of the graft was assessed by infusion of dopamine and an amino acid. The postnephrectomy GFR of donors in groups A and B were 74 +/- 18 and 72 +/- 20 ml/min/1.73 m2, respectively. The GFR of pediatric recipients was significantly lower than that of adult recipients at corresponding time points along the course of follow-up. The mean values of graft GFR were 47.6 +/- 20 and 63.8 +/- 29.6 ml/min/1.73 m2 for pediatric and adult recipients, respectively (P < 0.001). Moreover, the graft functional reserve was significantly lower in pediatric recipients. These data demonstrate that adult kidneys transplanted into pediatric recipients have lower GFR than those transplanted into adults, despite corrections for body surface area. Although the reason for this phenomenon is unknown, the observation may have important implications for management of pediatric recipients. PMID- 7992358 TI - Multicenter trial of Towne strain attenuated virus vaccine in seronegative renal transplant recipients. AB - The Towne strain of attenuated CMV vaccine was compared with placebo in seronegative renal transplants who later received kidneys from seropositive donors. This was a double-blind, randomized, placebo-controlled trial conducted at 3 different institutions. The results were consistent with 2 prior studies, in that whereas mild CMV disease was only slightly and insignificantly reduced in vaccine recipients, severe disease was markedly reduced. In the current study, all 4 severe cases of CMV disease occurred in placebo recipients, for an incidence of 17%, versus 0% in vaccine recipients (P < 0.03). Thus, prior immunization rendered seronegative patients more resistant to the effects of CMV infection. PMID- 7992359 TI - Course of Henoch-Schonlein nephritis after renal transplantation. Report on ten patients and review of the literature. AB - The frequency and the risk factors for clinical recurrence of Henoch-Schonlein nephritis following renal transplantation (TP) remain largely unknown. We report on 14 transplants performed at our center in 10 patients, detail the evolution of 2 of them with clinical recurrence, and review 64 other transplants reported in the literature. In our series, all patients are currently alive. Seven grafts are well-functioning 22-295 (mean, 97) months after TP without any sign of clinical recurrence. Five grafts were lost from rejection. Clinical recurrence occurred in 2 patients who were on cyclosporine/azathioprine/prednisone therapy. Pooling our series with that of Hasegawa et al., the actuarial risk for renal recurrence and for graft loss due to recurrence was 35 and 11% at 5 years after TP, respectively. In our series, duration of original disease was 2 and 28 months in the 2 patients with recurrence versus 31-144 months in the others without recurrence. In the literature, this duration was < or = 36 months in all 7 patients with recurrence. Recurrence occurred despite a > 12-month delay between disappearance of purpura and TP in our 2 patients and in 3 of 6 previously reported recurrences. We conclude that Henoch-Schonlein purpura nephritis frequently recurs after TP. Recurrence (1) seems to be associated with a shorter duration of the original disease, (2) can occur despite a delay of more than 1 year (as commonly advised) between disappearance of purpura and TP, and (3) is not prevented by a triple immunosuppressive regimen that includes cyclosporine. PMID- 7992360 TI - Factors influencing vertebral bone density after renal transplantation. AB - In an effort to determine the influence of immunosuppressive therapy and other clinical variables on posttransplant osteopenia, vertebral bone density was measured at least 6 months after transplantation in 65 adult primary renal transplant recipients receiving a variety of immunosuppressive regimens. Fifteen of the 65 patients (23%) had vertebral bone densities below a fracture threshold of 1.0 g hydroxyapatite/cm2. Multivariate analyses indicated that cumulative steroid dose and female gender were the major independent predictors of low vertebral bone density. In women, postmenopausal status also was associated with osteopenia. There was no correlation between cumulative cyclosporine dose and bone density. Results of this study indicate that posttransplant osteopenia is common in renal transplant recipients, including those treated with CsA. Although CsA has allowed the use of lower cumulative doses of steroids, concomitant steroid therapy remains the preeminent factor accounting for loss of bone density. PMID- 7992361 TI - One-year enzyme-linked immunosorbent assay follow-up of human interleukin for Da cells/leukemia inhibitory factor in blood and urine of 22 kidney transplant recipients. AB - The cytokine human interleukin for Da cells/leukemia inhibitory factor (HILDA/LIF) exerts multiple biological effects in vitro. In mice, high circulating levels of HILDA/LIF induce a wide range of pathophysiological events, some of them closely involved with immunological and inflammatory responses. Using a sandwich ELISA recognizing the natural human HILDA/LIF molecule with a threshold of 50 pg/ml in urine and 150 pg/ml in plasma, we monitored the urine and plasma HILDA/LIF levels of 22 patients in their first year after a kidney transplant. HILDA/LIF urine excretion is increased during acute rejection, and infections also trigger heavy HILDA/LIF plasma concentrations or urine excretion. In addition, this study raises the question of HILDA/LIF involvement in post kidney-transplant phenomena such as hypercalcemia, osteoporosis, or the reversal of anemia. PMID- 7992362 TI - Histological chronic allograft damage index accurately predicts chronic renal allograft rejection. AB - Chronic rejection has emerged as a major problem in renal transplantation, and clinical trials for prophylaxis and therapy are underway. Use of graft and patient survival as endpoints in prophylactic studies requires long follow-ups to read the endpoint. There is also an obvious need for a starting point for intervention studies. Previously, we formed a histological chronic allograft damage index (CADI), based on numerical scoring of histological alterations compatible with chronic rejection. Using protocol core needle biopsies of 89 functioning grafts 2 years after transplantation and a follow-up of 6 years, we demonstrate now that (a) the CADI at 2 years correlates significantly (r = 0.717, P = 0.0001) with transplant function at 6 years, and (b) that the CADI at 2 years reliably (P = 0.001) predicts the patients who will proceed to clinical chronic rejection later. As protocol core biopsy is an early predictive parameter for chronic rejection, our results suggest that a protocol core biopsy (at 2 years or possibly even earlier) should be included in all clinical investigative protocols dealing with chronic renal allograft rejection. PMID- 7992363 TI - Comparison of helper and cytotoxic antirecipient T cell frequencies in unrelated bone marrow transplantation. AB - Donor/recipient histocompatibility antigen differences initiate acute graft versus-host disease (GVHD) after bone marrow transplantation. Frequency analysis, using limiting dilution techniques, of functionally defined (helper or cytotoxic) antirecipient T lymphocyte precursors in the peripheral blood of the donor has been shown to be an accurate predictor for the development of moderate-to-severe acute GVHD. Here, we describe a sensitive assay for measuring alloreactive helper (IL-2-producing) T lymphocyte precursor (HTLp) frequencies, and compare the ability of this assay and the cytotoxic T lymphocyte precursor (CTLp) assay to detect HLA- class II and class I differences and to predict clinical outcome in a cohort of unrelated donor/recipient BMT pairs. Twenty-two pairs underwent unrelated donor BMT. Patients with high (> 1:100 x 10(3)) HTLp or CTLp frequencies had a higher incidence of moderate-to-severe (grades II-IV) acute GVHD (80% and 100%, respectively) than pairs with low (< 1:100 x 10(3)) frequencies (40% and 57%, respectively). Ten (45%) patients have died, but all patients with both a low HTLp and low CTLp frequency remain alive. The HTLp and CTLp assays provided similar predictive information for outcome. Given that the HTLp assay is more rapid and less labor intensive, it offers an additional or alternative functional method for donor selection in unrelated donor BMT. PMID- 7992364 TI - Pravastatin reduces serum cholesterol and low density lipoprotein concentrations following pancreas transplantation. AB - Hyperlipidemia is a significant risk factor for atherosclerotic vascular disease. We have shown previously that pancreas transplantation (PTX) improves but does not normalize lipids in most PTX recipients. We studied whether pravastatin was effective in treating 10 patients with elevated low density lipoprotein (LDL) cholesterol (LDL-C) following PTX. Seven men and 3 women were studied. Six received combined kidney-pancreas transplantations, while 4 received PTX alone. Age at time of PTX was 37.2 +/- 2.2 years (mean +/- SEM), and 4 had established coronary artery disease before PTX. Mean cholesterol (C), LDL-C, triglycerides (TG), and high density lipoprotein (HDL)-cholesterol (HDL-C) were 236 +/- 12, 142 +/- 6, 222 +/- 50, and 49 +/- 4 mg/dl before PTX. The LDL to HDL ratio was 3.0 +/ 0.3. After PTX, excluding the first 45 days, mean C, LDL-C, and HDL-C increased to 278 +/- 10, 178 +/- 7, and 63 +/- 6 mg/dl (all P < or = 0.05), respectively. TG, LDL to HDL ratio, and weight were unchanged. Pravastatin (11.7 +/- 0.8 mg/day, mean +/- SEM) was initiated 250 +/- 53 days after PTX. During therapy, C and LDL-C decreased on average to 231 +/- 10 and 134 +/- 8 mg/dl, respectively (both P < 0.01), while HDL did not change. The decreases in C and LDL-C were unexplained by a decrease in weight, cyclosporine dose or concentration, or increase in serum creatinine. However, prednisone dose decreased over the same interval, so a contribution from this variable cannot be excluded. No evidence of toxicity was identified during therapy. This is one of the first reports demonstrating that pravastatin is a safe and effective treatment for elevated C and LDL-C in patients following PTX. However, pravastatin did not increase HDL or decrease TG, as observed in the nontransplantation setting. Whether pravastatin or any hypolipidemia therapy can prevent cardiovascular events or mortality following PTX remains to be established. PMID- 7992365 TI - Influence of donor and histocompatibility factors on corneal graft outcome. AB - The Corneal Transplant Follow-up Study has followed 2311 penetrating keratoplasties for up to 450 days after transplant. A total of 207 failures were observed, including 65 classical rejections and 35 endothelial decompensations. At 12 months, graft survival was 89%, and survival free from rejection was 87%. For surviving grafts, risk of failure reduced from 4.8% in the first 75 days and stabilized after 5 months at 1.2% in each 75-day interval. Risk of rejection initially followed a similar pattern, but then increased after 12 months. Multifactorial analyses accounted for differences in recipient characteristics and interrelationships of donor factors. Donor age, sex, cause of death, and method of corneal storage were not found to influence significantly either time to graft failure or time to first rejection. Grafts in prospectively tissue-typed donor-recipient pairs were generally considered before surgery to be at increased risk of either graft failure or rejection. With due allowance, increasing risk of rejection was associated with increasing numbers of mismatches at HLA-A and HLA-B broad antigens. The opposite was true at HLA-DR broad antigens, where increased risk of rejection was observed with no mismatches. PMID- 7992366 TI - Differential effects of gallium nitrate on T lymphocyte and endothelial cell activation. AB - The immunosuppressive agents used clinically to prevent allograft rejection exert their effects by interfering with antigen-dependent T cell activation, endothelial cell function, or both. Gallium nitrate (GN) is immunosuppressive both in vitro and in vivo, and has potential for clinical use in transplant recipients. Therefore, we analyzed the influence of GN on gonadal vein endothelial cell (GVEC) and T cell activation. GVEC were stimulated with IFN gamma or TNF alpha in the presence or absence of GN, and tested for changes in levels of MHC class I, MHC class II, vascular cell adhesion molecule-1, and intercellular adhesion molecule-1 expression. GN did not interfere with the baseline or cytokine-enhanced expression of these molecules. Rather, it increased the expression of intercellular adhesion molecule-1 on GVEC, and this effect was further augmented in the presence of IFN gamma. In contrast, GN inhibited T cell proliferation stimulated by allogeneic GVEC or allogeneic monocytes in a dose dependent manner. In transwell experiments, GN blocked the induction of MHC class II expression on isolated GVEC caused by alloactivated T cells, but not by recombinant IFN gamma. This suggests that GN can interfere indirectly with inflammatory responses of endothelial cells by interfering with local T cell activation and lymphokine production. Once lymphokines are produced, GN does not interfere with their effects on endothelial cells. GN is thought to act through transferrin receptors, but GVEC, unlike T cells, do not increase their expression of transferrin receptors, after stimulation with cytokines. This may explain their relative lack of sensitivity to GN. In general, GN appears to stimulate endothelial cells but suppress T cells. This paradoxic effect suggests that therapy with GN may enhance T cell-independent inflammatory responses, such as cellular infiltration and repair of tissue damage, while suppressing T cell dependent responses, such as T cell-mediated tissue destruction and allograft rejection. PMID- 7992367 TI - Induction of natural chimerism after retransplantation of the liver in rats. AB - Immunological aspects after orthotopic rat liver retransplantation (re-OLT) were examined in association with cell migration and mixed chimerism. At day 2 after the first orthotopic liver transplantation (day 0) in the combination of DA (MHC haplotype, RT1a) donor into PVG (RT1c) recipient, the grafted DA liver was removed and a new PVG liver was implanted into the same PVG recipient (re-OLT). In the PVG recipient at various times after the re-OLT, DA-derived antigen and cells were detected using a DA-specific anti-class I mAb R3/13 in conjunction with ELISA, immunoblotting, and immunohistochemistry. The level of soluble class I antigen, which had risen to 270 ng/ml after the first OLT, substantially decreased within 24 hr after re-OLT. Using immunoblotting, DA class I antigen was detected in the PVG recipient's lymphoid organs at day 3 after DA liver grafting and persisted for up to 21 days after the DA liver was replaced by a new PVG liver. Immunohistochemistry on sections of spleen from re-OLT rats showed that the level of migratory cells expressing DA class I correlated with the findings obtained by immunoblotting. While the DA-derived antigen and cells were detected in the re-OLT recipient, the DA-specific inhibition of mixed lymphocyte reaction was observed in re-OLT serum. Our results suggest that the implanted DA liver graft was the source of DA soluble class I antigen, but DA-derived antigen and cells detected in the re-OLT recipient organs could persist for a relatively long time under immunosuppression after the implanted DA liver was removed by re-OLT. PMID- 7992368 TI - Orally administered immunosuppressants modify intestinal uptake of nutrients in rabbits. AB - The effect on intestinal nutrient transport of the immunosuppressive drugs cyclosporin A (CsA), cyclosporin G (CsG), and rapamycin (RAP) was determined in New Zealand white rabbits. Rabbits received oral doses of CsA (20 mg/kg/day), CsG (10 mg/kg/day), or RAP (1 mg/kg/day) for 10 days. Animals receiving RAP had decreased food intake and weight gain compared with controls. This correlated with a decrease in both total ileal weight and corresponding mucosal weight. CsA and CsG administration had no effect on food intake, total weight gain, or intestinal weight. Villus surface area was significantly decreased in all groups as compared with controls. Jejunal uptake of D-glucose as well as 1 medium and 4 long chain fatty acids was not affected by drug administration, while both mucosal-to-serosal and net 3-0-methylglucose fluxes were increased (P < 0.05) in the jejunum by all 3 drugs. In the ileum, the rates of uptake of D-glucose as well as stearic and linoleic acids were increased in animals treated with RAP compared with controls. There was an increase in the ileal values of the maximal transport rate (Vmax) and apparent Michaelis constant (Km*) in RAP, and a fall in the Vmax and Km* in CsG. CsG administration resulted in a decreased cholesterol uptake in both jejunum and ileum, and a decreased D-glucose uptake in the ileum compared with controls. These differences in glucose uptake among groups could not be attributed to variations in body, intestinal, or mucosal weights. It is unlikely that the changes observed in CsA- and CsG-treated animals would have nutritional importance, as these animals gained weight normally. In addition, in these animals the changes mainly occurred in the ileum, not in the jejunum, where most glucose is absorbed, and the associated alterations in the values of the Vmax and Km* would lead to reciprocal changes in the rates of uptake of varying luminal concentrations of glucose. In contrast, these changes are likely to be of more importance in RAP-treated animals, since they failed to gain weight normally. The significance of these findings needs to be established in chronically treated animals. PMID- 7992369 TI - Elastin expression in a model of acute arterial graft rejection. AB - Elastin is an important component of normal blood vessels and the extracellular matrix of atherosclerotic plaques, but its role in intimal thickening in the arteries of transplanted organs has not been defined. We have looked at elastin gene expression (by in situ mRNA hybridization) in an animal model using an abdominal aortic transplant between 2 strains of rats disparate for MHC class I antigens. The normal aortic wall of adult rats lacks elastin mRNA. Aortic allografts at 7 days after transplantation exhibit increased elastin mRNA in the medial vascular smooth muscle cells. This medial elastin mRNA expression is present only until 20 days after transplantation, and at later times, only the juxtaluminal cells of the neointima express elastin mRNA. Stainable elastin is detectable only in regions that previously demonstrated high levels of elastin mRNA. Combined in situ hybridization and immunocytochemistry reveals that most elastin mRNA-expressing cells in the media are alpha-actin-positive smooth muscle cells. In the neointima, elastin mRNA-expressing cells do not stain with antibodies to either smooth muscle alpha-actin or macrophage proteins. This cell population may represent a "synthetic" phenotype of vascular smooth muscle cell lacking alpha-actin protein. We presume there is immune cell-mediated injury leading to a vascular smooth muscle cell response and part of the vascular smooth muscle cell response may be increased elastin mRNA expression and elastin deposition in the allografts. PMID- 7992370 TI - Effects of exogenous interleukin-10 in a murine model of graft-versus-host disease to minor histocompatibility antigens. AB - IL-10 is a regulatory cytokine of both T cells and monocytes. We have investigated the ability of IL-10 to regulate responses to alloantigens in vitro and in vivo. Addition of IL-10 to mixed lymphocyte cultures profoundly decreased the proliferation and IL-2 production by donor B10.BR cells stimulated with CBA cells expressing minor histocompatibility antigens. Administration of IL-10 for a period of 2 weeks after bone marrow transplantation decreased the expansion of CD4+ and CD8+ donor T cells. In addition, splenocytes from BMT mice treated with IL-10 secreted less IFN-gamma after stimulation with Con A in vitro. The suppression of the mitogen-driven proliferative response of lymphocytes from the IL-10-treated group could also be reversed with significantly less anti-IFN-gamma antibody than for saline-treated controls. However, treatment with IL-10 was not sufficient to alter significantly the clinical course of graft-versus-host disease in CBA recipient mice as assessed by survival, weight loss, and splenomegaly. The results suggest that exogenous IL-10 suppresses the afferent Th1 response in a graft-versus-host reaction but does not significantly diminish the effector stage of graft-versus-host disease. PMID- 7992371 TI - Suppression of acute rejection prevents graft arteriosclerosis after allogeneic aorta transplantation in the rat. AB - Rat aortic allografts develop arteriosclerotic alterations in the vascular wall that are histologically similar to those observed in chronic rejecting vascular allografts. We used cyclosporine and rapamycin (RAPA) in two different rat strain aorta transplantation models to investigate the effect of immunosuppression on posttransplant graft arteriosclerosis. High dose CsA (25 mg/kg, 3 times/week) treatment significantly inhibited intimal proliferation in the "strong" WAG-BN model (P < 0.01) as well as in the "weak" BN-WAG combination (P < 0.001), compared with untreated allogeneic controls. In the latter combination, even fewer intimal lesions were present than in WAG autotransplants, suggesting that CsA may also inhibit the arteriosclerotic response to mechanical injury. RAPA (3 mg/kg, 3 times/week) was as effective as CsA in reducing intimal lesions (P < 0.01 and P < 0.001 in the BN-WAG and WAG-BN models, respectively). Low dose CsA (5 mg/kg, 3 times/week) was only partially effective in preventing intimal lesions. Histology of the nontreated allografts showed ongoing acute rejection in the adventitial layer. The degree of cellular infiltration correlated with the severity of arteriosclerotic lesions. High dose CsA and RAPA treatment prevented adventitial infiltration in both models, while low dose CsA was only moderately effective. In conclusion, in the present study, the degree of arteriosclerotic involvement after allogeneic aorta transplantation was related to the severity of cellular adventitial infiltration. The myointimal thickening was inhibited by effective immunosuppressive treatment. These observations may imply that chronic rejection develops after ineffective immunosuppression. PMID- 7992372 TI - Reduction of donor-specific cytotoxic T lymphocyte precursors in peripheral blood of allografted heart recipients. AB - Tolerance to allografted hearts in human recipients has been observed both in clinical situations and in in vitro experiments. To elucidate whether a quantitative change of alloreactive CTL is one of the mechanisms accounting for this graft tolerance, CTL precursor (CTLp) frequencies in the peripheral blood of 10 heart recipients were measured against spleen cells from donors and HLA nonidentical third-party persons. In this longitudinal follow-up study, we showed that the rejection reaction(s) in the grafted heart correlated with CTLp frequencies in samples taken before transplantation against the donor spleen cells, but not with the CTLp frequencies against the spleen cells from the third party persons. The CTLp frequencies against the spleen cells from donors decreased 4-6 months after transplantation, and remained at a low level afterward. However, the CTLp frequencies against spleen cells from third-party persons in blood samples obtained 1 year after transplantation were not significantly different from those before transplantation. Therefore, we conclude that donor-reactive CTLs are important in rejecting allografted heart. The decrease in donor-specific CTLp after transplantation could explain the donor specific tolerance. The decrease may be due to homing of the specific CTLp to the graft, or by clonal deletion of the donor-reactive CTL caused by chronic alloantigen stimulation in the presence of immunosuppressive therapies. PMID- 7992373 TI - Soluble HLA class II concentrations in normal individuals and transplant recipients. Comparison with soluble HLA class I concentrations. AB - We developed an ELISA to quantify soluble HLA class II (S-HLA-II) in 702 sera obtained from normal subjects, patients with end-stage renal disease, and recipients of renal, hepatic, and cardiac transplants. Concentrations of S-HLA-II were detectable in 124 of 126 normal individuals. The distribution of normal values described a monophasic curve with a skewed distribution. In transplant recipients, there were no differences between preoperative and posttransplant values, but values in liver patients were significantly higher than in kidney patients, and values for heart patients were lowest of all groups. There were periodic variations in concentrations in individual patients, but these were unrelated to rejection, infection, or any other apparent clinical event. S-HLA-II was consistently present in the urine. All of these observations contrast with previous observations concerning soluble HLA class I (S-HLA-I) molecules, which were almost the precise reverse. It seems likely that these clear differences in S-HLA-II and S-HLA-I concentrations relate to different physiologic processes in either production, function, or elimination. PMID- 7992374 TI - Stem cell regions in filiform papillae of tongue as targets of graft-versus-host disease. PMID- 7992375 TI - Transplantation in humans of encapsulated xenogeneic cells without immunosuppression. A preliminary report. PMID- 7992376 TI - Lymphocyte culture from endomyocardial biopsies. Effects of polyclonal T cell activators compared with interleukin-2 alone. PMID- 7992377 TI - Improved in vitro generation of epithelial grafts with oral mucosa. PMID- 7992378 TI - Dynamics of the expression of the interleukin-2 (IL-2) receptor in rat renal allografts analyzed by immunohistology, autoradiography, and nuclear imaging using radioiodinated IL-2 probes. PMID- 7992379 TI - Adenosine and ATP: from receptor structure to clinical applications. PMID- 7992380 TI - Novel receptor antagonists welcome a new era in endothelin biology. PMID- 7992381 TI - Dopamine D4 receptors: curiouser and curiouser. PMID- 7992382 TI - Problems associated with the partiality of a partial agonist. PMID- 7992383 TI - Theoretical treatment of one-agonist-two-receptor systems. PMID- 7992384 TI - An alternative model for bell-shaped concentration-response curves. PMID- 7992385 TI - Further mechanisms of non-genotoxic carcinogenesis. PMID- 7992386 TI - TH2 and 'TH2-like' cells in allergy and asthma: pharmacological perspectives. AB - Recently, considerable progress has been made in understanding the molecular basis by which cytokines released from CD4+ helper T cells contribute to allergic disease. A subset of CD4+ helper T cells, termed TH2 cells, produce interleukin 4 (IL-4) and IL-5, but not interferon gamma. IL-4 has a critical role in causing B cell immunoglobulin-isotype switch leading to IgE synthesis, and IL-5 governs eosinophilic inflammation of airway tissue. Studies on the mechanisms whereby TH2 cells, and non-T cells such as metachromatic cells, produce a highly restricted panel of cytokines has revealed molecular mechanisms that may affect our views on the induction and treatment of asthma, and these are discussed in this review by Gary Anderson and Anthony Coyle. TH2 cytokine biology may enable pharmacologists to design better, and perhaps even preventative, therapies for the treatment of asthma and allergy. Surprisingly IL-4, rather than IL-5, is emerging as a critical drug target owing to its central role in the regulation of CD4+ helper T cell phenotype commitment. PMID- 7992388 TI - Dissection of eukaryotic transmembrane signalling using Chlamydomonas. AB - Novel insights and surprises are often generated when investigators choose an organism that permits a new approach to a problem. For example, secretory and cell-cycle mutants in yeast have provided quantum leaps in elucidating these processes. Similarly, genetic systems are providing exciting new insights into signal transduction. The 'green yeast' Chlamydomonas has the potential to be a particularly rich organism for genetic analysis of signal transduction because, although unicellular, it has several interesting behaviours, which are discussed in this article by Lynne Quarmby and Criss Hartzell. Phototaxis results from the transduction of a light signal received by the eyespot to changes in flagellar beat. The mating reactions, which culminate in the fusion of gametes, are initiated in response to adhesion of flagellar proteins. Deflagellation, or flagellar shedding, is an acute response to a variety of stimuli. Molecular genetic analysis of behavioural mutants is providing new directions for understanding signal integration and segregation. PMID- 7992387 TI - Phenylglycine derivatives as antagonists of metabotropic glutamate receptors. AB - Metabotropic glutamate receptors represent a family of G protein-coupled receptors that can be activated by L-glutamate, the principal excitatory neurotransmitter in the brain. Until recently, progress in identifying the physiological and pathological roles of metabotropic glutamate receptors has been hampered by the lack of selective antagonists. In this article, Jeff Watkins and Graham Collingridge describe the pharmacology of, and initial physiological studies using, certain phenylglycine derivatives and related substances--the first definitive antagonists of metabotropic glutamate receptors. PMID- 7992389 TI - [Late sequelae after cancer treatment in children]. PMID- 7992390 TI - [Second cancer. Risk of a second malignant neoplasm in persons with cancer in childhood and adolescence]. AB - Cancer treatments in early life have in previous studies been associated in with high risks of developing a second malignant neoplasm. This study reports on the relative and attributable risks of second malignant neoplasms among 30,880 people under the age of 20, who had been identified in the files of any of the five Nordic cancer registers, 1943-1987. Overall, 247 cases of second malignant neoplasms were observed in 238 patients, yielding a relative risk for cancer of 3.6 (95% confidence interval 3.1-4.1). The risk changed significantly from 2.6 in people first diagnosed during the 1940s and 1950s to 6.9 among cohort members included in the late 1970s and 1980s. Highest levels of the relative risk were seen during the ten years immediately after first malignant diagnosis. The incidence of second malignant neoplasms attributable to the first cancer and associated treatments, however, showed a consistent rise throughout the 45 years of follow up. It was concluded that the estimated risks for second malignant neoplasms were significantly lower than those found in most large hospital based studies but compatible with the results from a similar population based study in the United Kingdom. Extent of risk and cancer pattern were similar among the Nordic countries and are believed to be representative for a large part of the European population. PMID- 7992391 TI - [Thyroid hormone autoantibodies. Characterization and clinical significance]. AB - Circulating autoantibodies against the thyroid hormones are a well-known phenomenon, which was first described in 1956. This article summarizes what is known about the prevalence in the population and the association with diseases and with the thyroid autoantibodies. Biochemical characterization has been performed in a number of studies. The pathophysiological effects are discussed. Clinically, the influences on the thyroid hormone assays are the most important aspect. PMID- 7992392 TI - [Endocarditis--clinical picture of native valve infection]. AB - In a population of 930,000 inhabitants all records of native valve infective endocarditis diagnosed in the decade 1980-89 were reviewed. One hundred and thirty-two cases were found, of whom 23 were not diagnosed until postmortem. Median prehospital duration of symptoms was 20 days (range 0-180) and median in hospital diagnostic delay five days (range 0-54). Known cardiac disease was found in 42%, possible portal of entry in 33%, but in 36% no predisposing factors were found. During the clinical course 55% experienced cardiac failure and 17% embolic episodes. Surgery was required in 19 patients. Of 111 culture positive cases, streptococci were found in 61 and staphylococci in 45 cases. Overall mortality was 33% with a mortality of clinically diagnosed cases of 18%. Native valve endocarditis is thus associated with a significant mortality in part due to significant diagnostic delays and a large number of post-mortem diagnosed cases. Only by securing a high level of alertness towards endocarditis can we expect a reduced mortality. PMID- 7992393 TI - [Quality assurance in postoperative pain treatment]. AB - One hundred and ninety-one patients were interviewed before and after surgery about their attitude toward and the quality of received pain relief. The nurses working in the same surgical units answered a questionnaire covering attitudes to postoperative pain and pain treatment. Forty-seven percent of the patients were in pain at the time of the postsurgical interview, 10% had not any analgesic prescribed at all, and 15% had received less than prescribed. Fifty-one nurses (71% of the total nursing staff) answered the questionnaire. Of these, 63% were sometimes in doubt about the physicians' prescriptions, 55% would occasionally refuse to give analgesics for various reasons, and 37% were not satisfied with the routines of pain control in their ward. Knowledge of pain treatment and communication between surgeons, anaesthesiologists, nurses and patients must be improved to make postsurgical pain relief adequate. PMID- 7992394 TI - [The disease panorama of emergency surgery in Maniitsoq 1991-1992. An epidemiological study and an evaluation of surgical results]. AB - In the district of Maniitsoq/Sukkertoppen, Greenland, an investigation was carried out to evaluate the extent of major surgical diseases seen in an epidemiological context. The number of patients submitted to major emergency surgery was 63, of which 61 were operated at the hospital of Sukkertoppen. The three main diagnostic entities were appendicitis, ectopic pregnancy and complicated delivery leading to cesarean section. Operative outcome was described, and the results were evaluated as satisfactory in the light of a very modest amount of per- and postoperative complications. The need for surgical preparedness must be taken into consideration by the authorities responsible for the recruitment of doctors and medical staff for district hospitals in Greenland. PMID- 7992395 TI - [Computer tomography in Greenland--a basis for establishment of the service]. AB - The purpose of this study is to evaluate the consequences of referral of patients for medical reasons from Greenland to Denmark for computed tomography (CT) scans. Twenty-eight of 35 evaluable patients could have been treated following the information from the CT scans without the use of the resources of a university hospital (for instance rehabilitation of patients with cerebral infarction). The establishment of a CT scanning service in Greenland may reduce costs without a deterioration in medical care. Accordingly, the alternative seems attractive. PMID- 7992397 TI - [Suicide in Denmark]. PMID- 7992396 TI - [Migrating clips--a complication of laparoscopic sterilization with Filshie clips]. AB - The most common method for female sterilization in Denmark is laparoscopic tubal application of Filshie clips. We describe a case of a 35 year old women admitted with a right inguinal abscess. A Filshie clips that had been inserted five years earlier was found by surgical exploration of the abscess. Possible pathogenetic and etiological factors are discussed. PMID- 7992398 TI - [Psychiatric patients and criminality]. PMID- 7992399 TI - [Forensic psychiatric patients--diagnosis, criminality and sanctions]. AB - During the last few years the number of persons who in connection with a breach of the penal code have been sentenced to psychiatric treatment has increased considerably. The case records of 38 such psychiatric patients have been reviewed with focus on diagnostic dispersion, patterns of abuse of alcohol and/or drugs and of crime. A majority of the patients (87%) had formerly been in contact with the psychiatric treatment system. At their latest psychiatric contact many (68%) were diagnosed as schizophrenic and were found to be involved in serious abuse of alcohol and drugs. The crimes committed consisted to a large extent of either real or potential injury to other persons. An unexpectedly large number of the patients had for a shorter or longer time been detained in custody. The examined criminal psychiatric clientele constitutes a strained group with a serious psycho pathology and with a high frequency of alcohol or drug abuse. More extensive investigations of these patients and possibly also of the effects of their pre trial detention would be desirable. PMID- 7992400 TI - [Dramatic decline in the incidence of gonorrhea and syphilis in Greenland--result of an intervention strategy?]. AB - During this century the incidence of gonorrhoea in Greenland has increased continuously and since the late 1960's syphilis has been reported with two epidemic peaks in 1976 and 1987. In 1986 a systematic intervention strategy was initiated consisting of 1) information and education, 2) enhancement of the attention of the medical profession to STD 3) critical evaluation of methods of examination and treatment 4) carefully performed partner notification and the use of epi-treatment of contacts in selected cases and finally 5) continued public information about the result of these efforts and the prevention of spread of HIV infection. Education was established in schools. Instructions for examination and treatment were renewed, special training was offered to health care personnel, and in 1988 a venereologist was employed by the Health Service. An almost constant decline in the incidences of both gonorrhoea and syphilis has now been demonstrated, which may easily be attributed to the above measures. However, it is uncertain whether the reduction is due to the improved treatment or a real change in sexual behaviour. Studies of knowledge and behaviour indicate that it is still necessary to influence attitudes to sexual behaviour, and to teach "safer sex" in order to further reduce the incidence of STD and to impede the spread of HIV. PMID- 7992402 TI - [Anesthesiological aspects of laparoscopy in gynecological surgery]. AB - A review of anaesthesia for gynaecologic laparoscopic surgery is given. Special criteria are needed for selection of patients, choice of anaesthesia and intraoperative monitoring. The cardiovascular and respiratory system are affected by tension from the pneumoperitoneum, absorption of CO2 and Trendelenburg position. Gas insufflation can provoke venous gas embolism, pneumothorax, pneumomediastinum, pneumopericardium and subcutaneous emphysema. The introduction of laparoscopic instruments may result in unintentional injuries to intra abdominal organs. The possibility that the procedure may have to be converted to open laparotomy needs to be considered. Bowel burns may result in perforation, peritonitis and sepsis. Laparoscopy is contraindicated in patients with serious cardiac disease, extensive bowel adhesions or intestinal obstruction. General anaesthesia with muscle paralysis, tracheal intubation and controlled ventilation is the preferred technique in these cases. Short acting anaesthetics are preferred in day case laparoscopy. Central neural blockade or infiltration anaesthesia supplemented with sedation and analgetics can be used for short laparoscopic procedures. The electrocardiogram, noninvasive arterial pressure monitor, airway pressure monitor, intra-abdominal pressure monitor, pulse oximeter and CO2 monitor are used routinely. Antiemetics and analgetics may be needed postoperatively. PMID- 7992401 TI - [Supravaginal or total hysterectomy?]. AB - There has been a decline in the rate of hysterectomies in Denmark in general over the last thirteen years, together with a rise in the number of supravaginal operations over the last two years. The literature concerning the relative merits of the supravaginal and the total abdominal operation is examined. It is concluded that the risk of developing carcinoma of the cervical stump is low, and no longer a weighty indication for the total in preference to the supravaginal hysterectomy as long as subsequent screening of the cervix is performed. At the same time it is important to inform the women carefully after the supravaginal operation in order to secure that subsequent screening actually is taking place. One must have a normal smear and offer a colposcopic examination before the operation. In general the rate of complications after both kind of hysterectomies is low. However, a few new studies indicate a reduced frequency of orgasm after the total hysterectomy compared with the supravaginal operation. When there are technical problems peroperatively with an increased urologic risk the supravaginal operation is recommended. PMID- 7992403 TI - [Is there a connection between size and risk of bleeding in unruptured intracranial aneurysms?]. AB - Of 1076 patients with intracranial ruptured aneurysms (RA), 948 had the RA verified by angiography, and of 908 RA with a maximum diameter less than 25 mm, 162 RA were < 5 mm, 474 were between 5-10 mm and 272 were between 11-24 mm. The average diameter of the RA according to the day of angiography after rupture did not differ significantly within the first 10 days. In these circumstances, using the indirect method for estimation of the risk of aneurysm rupture according to the size, we also recommend that unruptured aneurysms with a size 10 mm or less should be seriously considered for operative closure of the aneurysm. PMID- 7992404 TI - [Prognosis after ruptured intracranial aneurysm in men and women]. AB - Of 1076 patients with aneurysmal subarachnoid haemorrhage, 674 were females and 402 males. No significant differences between females and males were seen as regards age, clinical condition on admission, pre-existing arterial hypertension and number of rebleeds. Angiographically demonstrated vasospasm was seen with a significantly higher incidence in females, which may possibly explain a significantly poorer outcome in females compared to males, despite a much higher rate in females of internal carotid artery aneurysms which have a significantly better prognosis compared with aneurysms at other sites. PMID- 7992406 TI - [Is recurrent abdominal pain in children a symptom of hyperreactivity disorder?]. AB - Suggestions in the literature about a possible role of hypersensitivity in children with recurrent abdominal pain induced an open controlled investigation in twenty children with recurrent abdominal pain and in twenty healthy children. The purpose was to look for differences in the numbers of hypersensitivity markers in pain and control children. Hypersensitivity markers were defined in four areas: familial disposition to atopic disease, atopic disease in the child's history, atopic disease disclosed at a clinical examination, and elevated levels of blood eosinophils and serum immunoglobulin E antibodies to selected inhalant allergens and food allergens. In no child was abdominal pain provoked by specific food intake. The total number of markers in the pain children was 21, and in the control children 31. In spite of the small material it thus seems unlikely that hypersensitivity plays an influential part in the etiology of children's recurrent abdominal pain. PMID- 7992405 TI - [Familial aggregation of insulin-dependent diabetes mellitus in Denmark. A nation wide population study]. AB - This study aimed to assess the prevalence of familial aggregation of insulin dependent diabetes mellitus (IDDM), among Danish families with a diabetic child and to compare epidemiological data for familial and sporadic cases of IDDM children. All IDDM patients aged 19 years or less treated at paediatric departments or departments of internal medicine were identified and asked to complete a questionnaire regarding diabetes onset and family history. Of 1574 probands identified, 1419 participated (90.2%). Additional cases of IDDM were found in 12.8% of the families. Among these families, in 6.8% the father and in 2.1% the mother were diabetics and in 5.0% at least one of the siblings were diabetics. In familial cases the proband was significantly younger at diabetes onset, the parents were younger at birth of the IDDM child and no differences in gender were observed in contrast to sporadic cases, where more males were found. Thus, heterogeneity in epidemiological characteristics was observed between familial and sporadic cases. PMID- 7992407 TI - [Cholecysto-duodenal fistula. A cause of severe gastrointestinal hemorrhage]. AB - A unique case of haematemesis due to a pyloroduodenal ulcer caused by an erosion by a 3 cm gallstone impacted in the duodenal bulb is presented. This is the first case where the localisation of a severe haemorrhage due to a complication of a duodenal biliary fistula is identified. PMID- 7992408 TI - [Autotransfusion with Cell-Saver in orthopedic surgical patients]. PMID- 7992409 TI - [Lung cancer--better prognosis?]. PMID- 7992410 TI - [Examination programs in patients with colonic symptoms]. PMID- 7992411 TI - [Rectoscopy and Hemoccult-II as initial diagnosis. A procedure in patients with symptoms of irritable colon]. AB - The diagnostic accuracy for colorectal cancer (CRC) of rigid sigmoidoscopy and faecal occult blood test (Hemoccult-II) (H-II) was investigated in patients with irritable bowel syndrome in general practice in a three year period and the results were compared with those of the previous three years, where rigid sigmoidoscopy and double contrast barium enema (DCBE) were the initial preferred examinations. Colonoscopy was recommended in patients with positive H-II, but also in patients with repeated negative H-II within three months, provided that the symptoms persisted. CRC was detected in 141 of 630 patients with positive H II and in 52 of 8697 with negative H-II. The number of CRC's in the two study periods was similar, in spite of a pronounced reduction in DCBE's from 12,196 to 5656 and a small increase in colonoscopies from 3053 to 4127. It was concluded that the new strategy was no worse than the previous one and the major savings in DCBE's could be used to exchange the rigid sigmoidoscopy with a 60 cm flexible sigmoidoscopy, increasing diagnostic accuracy, shortening delay of diagnosis and removing more adenomas, which eventually may reduce the future incidence of CRC and thereby the mortality from CRC. PMID- 7992412 TI - [Treatment of dyskinetic syndromes]. AB - Dyskinetic syndromes are conditions with involuntary movements. They can have different causes, but are often due to dysfunction of the basal ganglias. The clinical picture varies but all show spontaneous alterations in intensity as well as deterioration with stress. This often leads to misjudgment of cases of dyskinesia. It is however important to be aware of these syndromes as medical treatment is effective in many cases. The treatment of tremor, tics, chorea, myoclonus, dystonia and medically induced dyskinesia is reviewed and the clinical pictures are briefly described. PMID- 7992413 TI - [Coagulation factor VII--new physiopathological and therapeutic aspects]. AB - Factor VII (FVII) is a vitamin K dependent coagulation factor that is synthesized in the liver, where clearance of the unactivated protein also takes place. It is a glycoprotein that following activation plays an important role in initiating coagulation after complex formation with tissue factor. A revised hypothesis of blood coagulation implicating the requirement of intact extrinsic and intrinsic pathways is presented. Increased activity of factor VII is associated with atherogenesis, and FVII deficiency may cause bleeding disorders. Recombinant FVIIa (rFVIIa) may be used in the treatment of haemophilic patients with antibodies against factor VIII or factor IX, utilizing its direct action in activation of factor X. Ongoing studies are investigating whether rFVIIa can shorten the bleeding time in patients with thrombocytopenia. PMID- 7992414 TI - [Preoperative laparoscopic evaluation of patients with upper gastrointestinal cancer]. AB - Nineteen consecutive patients with adenocarcinoma of the stomach or pancreas, in whom preoperative ultrasonography and computed tomography were unable to assess the possibility of surgical resection, had a diagnostic laparoscopy performed. In 16 cases the operability could be established from the findings at laparoscopy. All laparoscopies were carried out without major morbidity and with a short postoperative hospital stay. It is concluded that patients belonging to this category should have a diagnostic laparoscopy performed in order to avoid futile laparotomies, which in cases that are unsuitable for surgical treatment are associated with emotional stress, physical morbidity and a prolonged hospital stay. PMID- 7992415 TI - [Kawasaki disease. Incidence in Denmark during the period 1981-1990]. AB - The aim of the study was to estimate the incidence of Kawasaki's disease and to describe the clinical manifestations and the prognosis of the disease in children in Denmark during the period 1981-1990. In a register of all hospital admissions in Denmark, 99 patients were registered as having Kawasaki's disease. Of those, 89 patients fulfilled the clinical diagnostic criteria. The mean incidence of the ten year period was 1.0 per 100,000 children per year. The incidence of the disease decreased in the age group from zero to seven years after which it was rarely observed. Typical laboratory findings were hypersedimentation, leucocytosis and thrombocytosis. Eight children had cardiomegaly and three had electrocardiographic changes. Echocardiography was performed in 66 patients showing coronary artery aneurysms in nine patients (14%) (six boys and three girls). No further cardiac complications were found. PMID- 7992416 TI - [Epidemiology of Legionnaires' disease in Denmark. A comparative study]. AB - An epidemiological study of Legionnaires' disease in Denmark is presented. A high incidence of apparently sporadic cases of Legionnaires' disease in Denmark was found. The source of infection remains obscure in most cases. No outbreaks have been registered in Denmark, in contrast to most European countries. It is concluded that intensified surveillance, including monitoring of water distribution systems in hospitals, combined with an earlier etiological diagnosis might disclose more nosocomial cases. PMID- 7992417 TI - [Intrauterine insemination with donor semen. Treatment of involuntary childlessness caused by male infertility]. AB - Intrauterine insemination with cryopreserved donor semen was performed in 114 women in a total of menstrual 381 cycles during the period 1.2.1991 to 15.5.1993. Eighty-one pregnancies were recorded corresponding to a conception rate of 21% per insemination cycle. After ten cycles the probability of conception and expected delivery was respectively 96% and 86%. The results show that intrauterine insemination with donor semen is a good treatment for couples with male infertility. Ultrasonic measurement of the follicles and timing of hCG injection were used for optimal timing of intrauterine donor insemination. The quality of the semen used for insemination is important. It is recommended to inseminate with at least two million of spermatozoa where at least 20% have normal motility. PMID- 7992418 TI - [Treatment of episiotomy wound infections. Incision and drainage versus incision, curettage and sutures under antibiotic cover--a randomized trial]. AB - Conventional, "open" treatment of episiotomy wound infections was compared to incision, curettage and primary suture under antibiotic cover in a prospective, randomized study. During the period 1.5.1986-31.12.1988 there were 4154 vaginal deliveries with episiotomy, of which 20 (0.48%) became infected. Seventeen of these patients consented to enter the study. Median time for healing was 12 days following suture and 19 days after "open" treatment (not significant). Hospitalization time was the same in the two groups. No re-infections were seen. A need for vaginal plastic repair was found in three of nine of the conventionally treated patients and in none of the patients in the suture group (not significant). It is concluded that treatment of episiotomy wound infections with incision, curettage and primary suture under antibiotic cover is an attractive, safe ad convenient alternative treatment. PMID- 7992419 TI - [Severe respiratory depression after intake of a sustained-release morphine preparation]. AB - A case of severe intoxication in a 33 year-old male who chewed a tablet of sustained-release morphine is presented. It is emphasized that patients are informed of the correct method of intake, especially of sustained-release agents since these are most likely to cause intoxication due to their high content of active substance. PMID- 7992420 TI - [Life-threatening postoperative rectal hemorrhage after appendectomy]. AB - A case of life-threatening haemorrhage nine days after appendicectomy is described in a 51 year old previously healthy man. Coecotomy revealed a bleeding artery near the invaginated appendiceal stump. The bleeding artery was presumably an intramural branch to the appendix from the posterior coecal artery that had not been included in the primary appendiceal ligature. This artery was presumably electrocoagulated during the appendicectomy but bleeding ensued when the coagulated tissue sloughed. PMID- 7992421 TI - [Vibration-induced white toes]. AB - A case of vibration-induced white toes and subtle neuropathy in a man aged 46 years is presented. He used to work with his left foot placed on a vibrating pedal for two to three hours a day during 12 years, driving a small wagon at a mink farm. PMID- 7992422 TI - [Is coronary disease caused by an infection with Chlamydia pneumoniae?]. PMID- 7992423 TI - [Pelvic inflammation--pelvic pain]. PMID- 7992424 TI - [Quality assurance at an emergency unit]. PMID- 7992425 TI - [Moderate alcohol consumption and reduced risk of ischemic heart disease. A causal connection or a coincidence?]. AB - A negative association between light to moderate alcohol consumption and the risk of coronary heart disease has been documented in numerous ecological, case control and cohort studies. The observed association is in the order of a 40-60% reduction in risk among light to moderate drinkers. The epidemiological findings are consistent, and several plausible biological mechanisms by which alcohol could reduce the risk of coronary heart disease add support to the hypothesis that the association is casual. The epidemiological evidence confirms the wellknown risk of adverse health effects of alcohol consumption above one to two drinks a day for women and one to three drinks a day for men. PMID- 7992426 TI - [Ambulatory treatment of injuries]. AB - In Denmark as well as in other countries an increase in the number of minor trauma treatments has been observed. This increase has not been observed in major trauma, suggesting an alteration in people's behaviour after trauma. As a result, more people are seeking treatment after minor injuries without an increase in the number of accidents. Suggestions have been made to reorganize the treatment of minor injuries to keep expenses down, and the treatment of minor injuries in accident and emergency departments as well as in general practice has been described in prospective investigations, but comparative studies between trauma treatment in accident and emergency departments or general practice have not been made. Economical studies of benefits (or losses) in different structures of trauma treatment are scarce. Comparative studies between minor trauma treatment in accident and emergency departments and general practice including detailed economical analysis should be carried out before changes in treatment structure are made, and the effect of these changes should be carefully evaluated afterwards. PMID- 7992427 TI - [Quality development at an emergency unit--an intervention study based on consumer satisfaction]. AB - A study among the users of an emergency department was carried out to assess user satisfaction, based upon a questionnaire. The study was split into two periods, before and after a change in procedure in the emergency department, namely that a nurse was to give information about waiting time, make coordinations and fix an order of priority of patients (triage) in the waiting room. Fourteen hundred and twenty-six answers were received, 794 before and 632 after the change. The users questioned after this change of procedure felt that they had been better received, that they had waited for a shorter time and described a better general experience as compared to the users questioned before the change, these differences were significant. There were no difference between the two groups concerning opinions on information about diagnosis, treatment and outcome, whether there was enough time for examination, treatment and information, whether the staff were obliging or whether their expectations had been fulfilled. It is concluded that such changes in procedure in the emergency department are to be recommended. PMID- 7992428 TI - [Structure of emergency units in Denmark 1985-1992]. AB - The aim of the study was to investigate the changes in trauma treatment structure in Denmark during the period 1985-1992. The design was a repeated cross-sectional analysis performed as a questionnaire in 1985, 1989 and 1992 given to the heads of the medical staff of all accident and emergency departments in Denmark. The analysis showed that the number of accident and emergency departments was reduced from 81 in 1985 to 69 in 1992. The median number of annual patient contacts increased from 5911 (150-50,000) to 8757 (150-47,000) over the period. The median number of inhabitants in the uptake-areas of the accident and emergency departments increased from 50,000 (4500-230,000) to 67,000 (4500-230,000). Only at 12 accident and emergency departments (with 1,183,000 inhabitants) was prehospital treatment given by medical doctors to trauma patients. Only one accident and emergency department used trauma scores routinely, and 29 (42%) used the Glasgow Coma Scale as a routine. It is concluded that there has only been a minor centralisation in trauma treatment structure in Denmark over the period 1985-1992, and there are still many accident and emergency departments with relatively few annual patient contacts. Prehospital treatment by medical doctors is still not routine in most areas of Denmark. PMID- 7992429 TI - [Referrals to an emergency unit before and after changes in the practitioner-on call system]. AB - Attendance at the casualty department of the Central Hospital in Naestved was investigated during two similar periods before and after changes were made in the practitioner-on-call system. The total number of patients admitted (either via casualty or referred from a practitioner) were registered. A total of 4454 attendances took place during the two periods, 2330 of these being before the changes and 2123 after the changes in the practitioner-on-call system. In the present material there were 1673 orthopaedic and 136 medical patients before and 1552 orthopaedic and 133 medical patients after the reorganization. No changes in medical specialities of the attendances in the two periods could be pointed out. 2110 patients were admitted to hospital in the first period, 2299 in the second period. The study concludes that no changes in the pattern of attendance at the casualty department could be shown after the reorganization in general practice. PMID- 7992430 TI - [A closed emergency unit. Consequences for referral patterns and economics]. AB - During the mid 1980's the emergency-room at Faaborg Hospital changed status from being open to semi-closed. From then on the patients had to contact a general practitioner before going to the emergency-room. The general practices in the area were then supposed to have a referring function. We decided to evaluate the consequences of this decision in 1991. From 25 August to 1 December 1991 we registered all patients who contacted the emergency-room. The conclusions were that no changes in the types of patients had occurred, and that it was at a greater cost to the National Health Service. PMID- 7992431 TI - [Injection site for quick-acting insulin. Significance for glycemic control in basal bolus insulin regimen]. AB - The impact on glycaemic control of soluble insulin injected either intramuscularly into the thigh (IMT), subcutaneously into the abdominal wall (SCA) or subcutaneously into the thigh (SCT) was evaluated in 49 Type 1 diabetic outpatients following a randomised three-month intervention study. Insulin doses were adjusted based on patients' self-monitored blood glucose values and reported hypoglycaemic episodes. More patients in the SCA and IMT groups than in the SCT group had serum fructosamine values within normal limits following intervention. Blood glucose at 03.00 was lower in the SCT group than in the SCA and IMT groups, due to a higher number of low nocturnal blood glucose values (less than 4 mmol/l) in the SCT group. In conclusion, s.c. injection of soluble insulin into the abdominal wall or intramuscularly into the thigh is preferable compared to s.c. injection into the thigh in the basal bolus insulin delivery regimen. Soluble insulin injection s.c. into the thigh during daytime is a risk factor for nocturnal hypoglycaemia. PMID- 7992433 TI - [A trial to prevent development of renal disease]. PMID- 7992432 TI - [Adolescent idiopathic scoliosis among girls in the Herning region. A follow-up of girls with adolescent idiopathic scoliosis found in an earlier screening at school]. AB - A nine year follow-up study of 76 females was carried out to investigate the spontaneous course of adolescent idiopathic scoliosis. The subjects were selected in an earlier epidemiological investigation by a screening (forward bending test and Moire topography) of 989 girls aged 10-17 years. A prevalence of 7.7% was found (76 girls). Four scolioses progressed to treatment (0.4%). Of the rest (72 girls) forty girls (55.6%) participated fully in the follow-up investigation involving clinical examination, Moire topography and X-ray examination. Of these 22.5% had thoracic, 37.5% had thoracolumbar and 40.0% had lumbar curve. The median size of the Cobb-angles was initially 10.1 (5-31) and at follow-up 8.5 degrees (0-30). A progression of more than four degrees was seen in 12.5%. The rest were unchanged or showed regression. None of the subjects needed treatment at any time. We found no indicators for the different spontaneous courses in untreated mild idiopathic scoliosis. Neither topography of the scoliosis, initial curve size nor age at the investigation-start showed corellation with curve behavior. PMID- 7992434 TI - [Travel insurance and chronic diseases]. PMID- 7992435 TI - [Pain in children]. PMID- 7992436 TI - [Winter depression and light therapy]. AB - Winter depression (Seasonal Affective Disorder, SAD) is a depressive illness, which starts in the autumn and disappears in the spring. The depression is, in contrast to the typical endogenous depression, characterized by increased appetite with carbohydrate craving, and increased sleep. There is an increase in the frequency of the illness towards the geographical poles. About 80% of the patients are women. The most remarkable aspect of the depression is however, that it can be effectively treated with bright light, given two hours daily for one to two weeks. A number of biological functions are currently under investigation in relation to winter depressions; among these are the metabolism of melatonin, various diurnal rhythms and the serotonergic system. PMID- 7992437 TI - [Biofilm, foreign bodies and chronic infections]. AB - Most bacteria occur in the environment as sessile cells adhering to a surface, whereas a minority exists as free floating (planktonic) cells. Biofilms consist of microcolonies embedded in a polysaccharide matrix produced by the bacteria. This polysaccharide slime protects the bacteria against hostile environmental factors. Planktonic daughter cells are liberated from the surface of biofilms and may colonize new surfaces and subsequently produce new biofilms. Biofilms are often consortia of several different bacterial species. The normal microflora on the skin or on the mucous membranes in the human body occurs as a biofilm, which is removed by the shedding of old cells and by the excretion of mucus. Subsequently new cells and new mucus are colonized by biofilm forming bacteria without giving rise to any symptoms. When body surfaces with a normally occurring microflora (A) are connected by means of an implanted foreign body with body surfaces or tissue compartments without a microflora (B) e.g. bronchi, gall bladder, peritoneum, veins, then a translocation of the normal microflora from (A) to (B) may easily occur leading to acute infection, formation of new biofilms on the implanted foreign body and induction of inflammation in the environment of this biofilm. Chronic bacterial infections are frequently caused by biofilm producing bacteria and the pathogenesis of the tissue damage is dominated by a persistent immune complex mediated inflammation. Bacteria growing in biofilms cannot be eradicated by antibiotics and biofilms resist the immunological and non specific defence mechanisms of the body.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7992438 TI - [Consultation-liaison psychiatry--the clinical couterpart of psychosomatics]. AB - Consultation-liaison psychiatry (C-L psychiatry) was founded in the USA in the 1930's as a clinical pendant of Psychosomatic medicine. By support and grants provided from the NIMH (National Institute for Mental Health) during the 1970's and 1980's, C-L psychiatry has now become an integrated part of the health care system in the USA. C-L psychiatric services are now being established in some European countries also. The aim of this review has thus been to introduce the C L psychiatry sub-specialty to a Danish audience. PMID- 7992439 TI - [Kasabach-Merritt syndrome]. AB - Kasabach Merritt syndrome, first recognized in 1940, is characterized by haemangiomatosis, thrombocytopenia and intravascular coagulation. It is most often seen in children, rarely in adults. The mortality rate is 20-30%. Treatment is by removing the haemangiomatosis and correcting the consumptive coagulopathy. The purpose of this paper is to present a patient with Kasabach Merritt syndrome with haemangiomatosis in the spleen and the liver. A review of the relevant literature is given. PMID- 7992440 TI - [Risk of cataract surgery in patients with myopia. A prospective Danish multicenter study with special reference to a complication]. AB - A prospective Danish multicentre study was conducted to evaluate the incidence of retinal detachment after cataract extraction in myopic eyes (axial length, > or = 25.5 mm). Two hundred and forty-seven cataract extractions in myopic eyes were reported during a period of 13 months. Two hundred and forty-one eyes underwent extracapsular and six eyes intracapsular cataract extraction. The mean follow-up time for 158 eyes was seven months (ranging from 1-30 months). In five cases a retinal detachment was observed, one case was probably present preoperatively, this person had undergone intracapsular cataract extraction. The incidence of retinal detachment was thus 1.62-2.02% in the total material and 1.66% in eyes operated with extracapsular cataract extraction. PMID- 7992441 TI - [Orthopedic ambulatory surgery. A study of patient satisfaction]. AB - One hundred and eighty-two patients who underwent ambulatory orthopaedic surgery received a questionnaire, 168 (92%) answered. Fourteen patients (7.7%) had to stay in hospital for one to three nights. One hundred and forty-seven (87.5%) found it acceptable to be discharged the same day, and 145 (86.3%) would prefer ambulatory to stationary treatment in case of new surgery. PMID- 7992442 TI - [Ultrasonic evaluation of peri-intestinal lymph nodes in patients with colorectal cancer]. AB - The aim of this study was to compare the number of lymph nodes detected by sonography with the actual number and nature of the lymph nodes found on histopathological examination. Twenty colorectal specimens with carcinoma were studied. Sonography was performed with the bowel submerged in water and pericolonic lymph nodes were marked on a drawing of the specimen. After fixation, pericolonic lymph nodes were identified by palpation and their location and size were noted on a similar drawing. By comparing the sonographic and histological findings it was possible to determine which nodes had been identified by sonography. Histological examination detected 205 lymph nodes in the 20 specimens. Sixty-four of them (31%) were found by in vitro sonography (25% of the benign nodes, 56% of the malignant nodes). Preoperative endosonographic assessment (performed in 10 of the patients) generally showed fewer lymph nodes than what was subsequently found by in vitro sonography. The inability of sonography to detect more than 56% of the metastatic lymph nodes makes preoperative endosonographic assessment less valuable than hitherto believed. PMID- 7992444 TI - [Bacterial endocarditis at a county hospital department, 1983-1992. Prognosis in relation to bacteriology, disease localization and treatment]. AB - The case records of 69 patients with a diagnosis of bacterial endocarditis were reviewed. Forty-nine patients had native valve endocarditis (NVE) and 20 patients had prosthetic valve endocarditis (PVE). Among patients with NVE left-sided endocarditis was treated surgically more often than right-sided endocarditis. Involvement of the aortic valve was the most important indicator of death and acute/subacute surgical intervention. The mortality was 29%. No patient with right-sided endocarditis died. The infective agent did not seem to influence outcome or frequency of surgical intervention. Among patients with PVE the most frequently isolated organism was coagulasenegative staphylococci. Surgical intervention occurred most frequently in those with infection with coagulase negative staphylococci or culture negative endocarditis. The mortality was 25%, identical for early and late cases. The patients who died were all infected with staphylococci. The localization did not seem to influence treatment or outcome. In spite of advances in surgical and medical treatment bacterial endocarditis is still a life-threatening disease with a high mortality. PMID- 7992443 TI - [Ion generators and bronchial asthma. A double-blind placebo controlled study]. AB - In this double blind, placebo-controlled study we examined the value of using a device for ionizing the air in the immediate environment as a therapy for asthma bronchiale. Nineteen adult patients with stable, reversible asthma were randomised to blind treatment with either an active device or an inactive placebo device. After four weeks treatment the patients were given the alternative device for another period of four weeks. We measured daily peak-flow, symptomscore, use of medicine and spirometry and found no differences between the two periods. Therapy with ionization of the environmental air in patients with bronchial asthma should not be recommended. PMID- 7992445 TI - [Left ventricular hypertrophy in patients with aortic stenosis. A comparison between electrocardiography and echocardiography]. AB - Using echocardiography (ECHO) as the reference method, the aim of this study was to determine the sensitivity, specificity, and predictive value of the electrocardiogram (ECG) in detection of left ventricular hypertrophy (LVH) in patients with aortic stenosis. Forty-one patients, 18 men and 23 women aged 25-80 years (mean 49 years) with uncomplicated aortic stenosis were studied. ECG-LVH was estimated by standard fixed voltage criteria. ECHO-LVH was defined according to left ventricular mass (LV mass) calculated by the Penn method. In the total material, the correlation between ECG-LVH and ECHO-mass was poor (r = 0.56, p < 0.05). The sensitivity and specificity of the ECG was respectively 50% and 100%. The positive predictive value of the ECG in detection of LVH was high (100%). We conclude that the sensitivity of the ECG in detection of LV hypertrophy is unsatisfactorily low. Accordingly, it is recommended that echocardiography be performed in all patients suspected of aortic stenosis. PMID- 7992446 TI - [Physical exercise as a supplement to diet. Effect on body composition, resting metabolic rate and cardiovascular risk factors in postmenopausal overweight women]. AB - One hundred and twenty-one healthy, overweight, postmenopausal women were randomly assigned to three groups: controls (no intervention), a 4200 kJ/day diet, or 4200 kJ/day diet with combined aerobic and anaerobic exercise, for 12 weeks. One hundred and eighteen women completed the study. The loss of weight was similar in the two intervention groups, but compared with the diet-only group, the diet-plus-exercise group lost significantly more fat (7.8 vs 9.6 kg) and no lean tissue mass (1.2 vs 0.0 kg). The resting metabolic rate was increased in the diet-plus-exercise group as compared to the controls (11% vs 4%, p < 0.009). The cardiovascular risk factors (serum lipids and lipoproteins (except high density lipoprotein), systolic blood pressure, and the waist-to-hip ratio) decreased significantly in both intervention groups, as compared to the controls. There were no consistent, major differences between groups in changes in total body, spinal, or forearm bone mineral density. In conclusion, overweight postmenopausal women benefit from addition of combined aerobic and anaerobic exercise to an energy-restrictive diet. PMID- 7992447 TI - [Subacute thyroiditis in Parvovirus B19 infection]. AB - In a 32-year-old women with clinical and scintigraphic signs of thyroiditis, serological screening showed positive IgG and IgM titres against Parvovirus B19 (PB19). Subacute thyroiditis has not previously been reported following PB19 infection. The present case suggests that subacute thyroiditis may be caused by PB19 infection. Further screening is necessary to establish whether this infection is more frequently associated with subacute thyroiditis than previously thought. PMID- 7992448 TI - [Liver infarction diagnosed by CT in a patient with dissecting thoracic aorta aneurysm]. AB - The CT appearance of hepatic infarction is only described in a few cases in the literature. The description is of well circumscribed areas of low-attenuation, often wedge-shaped and extending to the periphery of the liver. We present a case where infarction of the liver, caused by a dissecting aneurysm of the aorta, was diagnosed by CT-scanning. Our CT scan revealed large, confluent, poorly circumscribed and hypodense areas in the liver consistent with an atypical appearance of hepatic infarction. The patient died shortly after the scanning, and autopsy confirmed infarction of the liver. PMID- 7992450 TI - [Acute brain syndrome after mefloquine treatment]. AB - It is known that the antimalarial drug mefloquine may cause neurological side effects. Only few cases of encephalitis ascribed to mefloquine treatment have been reported. We here describe a 34 year-old female patient with symptoms of acute brain syndrome. The patient was initially treated with mefloquine for infection with P. falciparum. She was rehospitalized 12 days after mefloquine treatment with fever, nausea, dizziness and headache. Her condition worsened and her temperature rose and 15 days after treatment she had generalized convulsions and went into a coma. The EEG was severely abnormal. The patient was discharged 37 days after mefloquine treatment, but it was two months before the EEG was normal and the patient in her usual condition. PMID- 7992449 TI - [Aggressive fibromatosis]. AB - Fibromatosis can be classified in two groups: Superficial fibromatosis without capacity for infiltration and deep fibromatosis with variable capacity for infiltrative growth. One of the deep fibromatoses is aggressive fibromatosis which is a local infiltrating process never known to metastasize. Two cases of aggressive fibromatosis are presented and histological characteristics and prognosis are reviewed. Once the diagnosis aggressive fibromatosis is established, surgical removal of the lesion by large excision is the only sufficient treatment. PMID- 7992451 TI - [Does long-term treatment with omeprazole increase the risk of cancer?]. PMID- 7992452 TI - [Chronic pelvic pain]. PMID- 7992453 TI - [Sexually transmitted diseases in Greenland]. PMID- 7992454 TI - [The nephrological misery]. PMID- 7992455 TI - Pyelonephritis: renal urokinase activity in rats on essential fatty acid diets. AB - This study was undertaken to assess whether additions of different oils to the diets of male rats would affect the renal urokinase (UK) activity of healthy and pyelonephritic kidneys. Four groups of fatty acid diets were studied: fat-free, coconut oil, fish oil and evening primrose oil (EPO). Pyelonephritis was obtained by unilateral extrarenal urinary obstruction and subcutaneous injection of Escherichia coli. The UK activity of the non-obstructed kidneys did not differ statistically between rats infected and not infected with bacteria (P > 0.056), except within the coconut oil group. A statistically decreased UK activity was obtained with bacteria injected animals on a coconut oil diet (P < 0.0001). This phenomenon, namely a decrease in UK activity, was also seen with pyelonephritic kidneys of rats on fat-free, coconut and fish oil diets (P < 0.0065). However, the UK activity of the obstructed kidneys with and without infection in the EPO group remained similar (P = 0.8477). These results suggest that the UK activity in infection-induced renal stones may be restored by EPO containing diets and may be of high relevance in the prevention and treatment of infection-induced renal stones. This revelation now needs to be more fully investigated. PMID- 7992456 TI - Urinary Tamm-Horsfall protein as a marker of renal transplant function. AB - In a total of 428 urine samples collected from 15 patients aged between 23 and 60 years after cadaveric kidney transplantation during a postoperative hospital stay, Tamm-Horsfall protein (THP) was quantitatively determined using the ELIAS SYNELISA-THP immunoassay. All patients were treated with azathioprine, cyclosporine, prednisolone, given an intraoperative high-dose single antilymphocyte globulin bolus and discharged with functioning grafts. In clinically uncomplicated courses, even after immediate transplant function, the recovery of graft function took on average 7 days. Thereafter the urinary THP excretion was relatively stable and amounted, on average, to 14.5 +/- 4.9 mg/24 h (i.e. was at the lower limit of normal urinary THP excretion). In cases of delayed onset of graft function of undetermined origin accompanied by extremely reduced urinary THP excretion, the functional recovery, whether spontaneous or brought about by treatment, was characterized by a continuous increase in urinary THP excretion. In connection with interstitial rejections urinary THP excretion seems not to be a recommendable diagnostic parameter. Daily measurement of urinary THP is, however, suitable for monitoring the functional state of transplanted kidneys. PMID- 7992457 TI - Nonuniform sampling of urodynamic signals: a comparison of different methods. AB - Several different techniques for urodynamic signal compression have been proposed in the last few years. Using these techniques it is possible to reduce the requirements for digital storage or transmission. There are a number of applications where it is essential to use such techniques in diagnostic and ambulatory urodynamics. The purpose of this study is to compare different techniques of urodynamic data compression. The so-called FAN, voltage triggered, two point projection and second difference methods. The comparison between the methods is based on 65 pressure, 46 uroflow and 18 surface electromyogram signals. The reduction ratio achieved for different allowable errors between the original and compressed signals is calculated and compared for the different techniques. Results show that it is possible to store urodynamic signals accurately at a low sampling rate, where FAN and voltage triggered methods seem to be superior to the rest. PMID- 7992458 TI - Transrectal ultrasound of the prostatic urethra related to urodynamically assessed urethral resistance. A pilot study. AB - In this pilot study on 17 men who underwent urodynamic investigation for various dysuric complaints, real-time transrectal ultrasonography (TRUS) was performed. From the images anatomical parameters were identified that correlated with obstructive urodynamic findings and urethral resistance parameters based on pressure-flow analysis. This study gives support for further clinical investigations to determine the value of TRUS for male patients with dysuric disorders. It also illustrates the anatomical basis of prostatic obstruction as quantified by objective urodynamic parameters. PMID- 7992459 TI - Perineal nerve stimulation for urinary sphincter control. Experimental study. AB - The effect of electrostimulation of the perineal nerve on the external urethral sphincter (EUS) and urethral pressure was studied in 9 dogs. The nerve was displayed in the ischiorectal fossa through a para-anal incision and an electrode was applied to it. Perineal nerve stimulation effected an increase of the urethral pressure (P < 0.01) and EMG activity of the EUS (P < 0.01), but not of the vesical pressure (P > 0.05). The greater the stimulus frequency, the higher the rise of the urethral pressure and EUS activity up to 50 Hz beyond which no further increase occurred. The duration of response diminished with increased frequency, the shortest being at 80 Hz (P < 0.001). The latency of the response decreased with increased stimulus frequency (P < 0.05). In terms of force and speed of contraction, stimulus frequency of 50 Hz evokes the most adequate EUS contraction. An off-time of double the stimulation phase allows indefinite re stimulation. Chronic electrostimulation of the perineal nerve may restore the sphincter tone so that perineal stimulation could be dispensed with. PMID- 7992460 TI - Experimental investigation of an infolded bowel segment as an anti-incontinence mechanism without interposing the ileo-cecal valve. AB - A technique for using bowel segment as an anti-incontinence mechanism was developed in an animal model and evaluated urodynamically. Variously modified bowel segments were investigated alone and later attached to a colonic reservoir to establish their value in preventing urinary incontinence while allowing easy catheterization. Using careful surgical technique, intussuscepted, tapered and plicated bowel segments were constructed. The maximum segmental closure pressure and functional length were evaluated in all preparations. The three bowel segments remained continent during slow filling and up to reservoir capacity. The recordings demonstrated both highest maximal closure pressure and longest functional length in the plicated system when evaluated both alone and following reservoir attachment. These recording differences occurred both with the reservoir full and empty. These results demonstrate the value of a plicated bowel segment in the maintenance of urinary continence when attached to a compliant urinary reservoir without using the ileo-cecal valve in this model. PMID- 7992461 TI - Effect of combined supplementation of magnesium oxide and pyridoxine in calcium oxalate stone formers. AB - A combined supplement of magnesium oxide (300 mg/day) and pyridoxine.HCl (10 mg/day) was given p.o. to 16 recurrent calcium oxalate (CaOx) stone formers, and its therapeutic efficacy was biochemically evaluated by measuring various parameters of blood (Na, K, Mg, urea, creatinine, calcium, phosphate, uric acid, alanine transaminase, aspartate transaminase and alkaline phosphatase) and urine (volume, pH, creatinine, Na, K, Mg, uric acid, calcium, phosphate, oxalate and citrate) at 0, 30, 60, 90 and 120 days of treatment. Serum Mg significantly (P < 0.01) increased after 30 days of treatment and remained constant thereafter while other blood parameters were unaltered. Combined treatment led to a significant increase in the urinary excretion of Mg and citrate over pretreatment values while oxalate excretion showed a gradual and significant decline during the therapy. The results confirmed the efficacy of MgO-pyridoxine supplementation in terms of changes in urinary excretion of lithogenic and inhibitory components, leading to a significant (P < 0.01) decrease in CaOx risk index from 0.09 +/- 0.04 at 0 day to 0.05 +/- 0.02 after 120 days of treatment. PMID- 7992462 TI - Measurement of BBN-induced alterations in rat urothelium by electron microscopic X-ray microanalysis. AB - The aim of this study was to analyse N-butyl-n-butanol-4-nitrosamine (BBN) induced alterations of the urothelium in rats concerning its content of phosphorus, sulphur, chlorine, potassium and calcium using electron microscopic X ray microanalysis (REM analysis). The following histopathological findings of the bladder mucosa were discovered after exposure to BBN: normal urothelium (n = 36); focal epithelial proliferations (n = 12) following 6-12 week's exposure; epithelial hyperplasia (n = 8) after urothelial carcinoma (n = 4) following 12 weeks' exposure. The observed phosphorus/sulphur and phosphorus/calcium ratios based on REM analysis did not show any statistical correlation with the morphological changes classified by light microscopy. Our data do not support the hypothesis raised by other investigators that an increase in phosphorus content or phosphorus/sulphur or phosphorus/calcium ratio could indicate early neoplastic transformations of urothelial cells as "tumor markers". PMID- 7992463 TI - Effects of selected chemotherapeutic agents on PCNA expression in prostate carcinoma cell lines. AB - Bivariate flow cytometric analysis of proliferating cell nuclear antigen (PCNA) was performed on prostate carcinoma cell lines (PC-3, DU-145). For both cell lines 100% methanol fixation provided optimal fluorescence intensity of PCNA. The ratio of PCNA/DNA increased in late G1 through early S/phase, followed by a decrease in mid- and late S and enhancement in G2/M phase. PCNA expression was increased in G2/M phase cells treated for 48 h with vinblastine. A slight decrease in PCNA expression was observed with cyclohexamide treatment. Hydroxyurea induced an increase in S-phase fraction along with enhanced PCNA expression. Methotrexate and Adriamycin had little effect on the cell cycle compartments of PC-3 or DU-145; however, methotrexate decreased PCNA expression, while Adriamycin enhanced it. Cisplatin increased S-phase in both cell lines, increasing PCNA expression in PC-3 and decreasing it in DU-145 cells. The data on the effects of drug treatment point to a dissociation between PCNA expression and S-phase fraction as calculated from the DNA distribution. In some cases, e.g., the cisplatin studies, different effects were obtained in the two different cell lines treated with the same drugs. Whether changes in PCNA expression will provide more useful information than S-phase fraction for evaluation of potential antitumor drugs is not known. PMID- 7992465 TI - Pathological and morphometric assessment of testicular parameters in patients with metastatic prostate cancer following treatment with either the antiandrogen Casodex (ZM176,334) or bilateral orchidectomy. AB - Casodex is an orally active non-steroidal antiandrogen that is highly selective for androgen receptors in animals and man. It is indicated for the non-surgical treatment of advanced prostate cancer in man. The present open controlled study in 13 Casodex-treated and 21 orchidectomy-alone (control) patients addressed the hypothesis that chronic administration of antiandrogens will result in Leydig cell hyperplasia as a result of feedback inhibition of the pituitary resulting in increased luteinising hormone (LH) stimulation of Leydig cells. Although Casodex has been shown to produce a moderate rise in circulating plasma testosterone concentration on chronic treatment in prostate cancer patients, a controlled histopathological and morphometric assessment of the testis following orchidectomy in relapsed Casodex patients showed no effect on Leydig cell populations compared with an orchidectomy alone (control) group. No evidence for induction of Leydig cell hypertrophy or hyperplasia as a result of chronic oral administration of 50 mg Casodex daily was obtained in this study. PMID- 7992464 TI - Effects of isoniazid (INH) on the BCG-induced local immune response after intravesical BCG therapy for superficial bladder cancer. AB - Because recent investigations showed that the use of isoniazid (INH) severely impaired the local immune reaction to intravesical bacillus Calmette-Guerin (BCG) in the bladder of guinea pigs, in this study the effect of INH in man has been investigated. Patients were treated with BCG with or without oral INH. The concentration of free INH in most urine samples of patients treated with BCG/INH was much higher (mean 38.0 +/- 60.9 micrograms INH/ml) than the minimal inhibitory concentration (MIC; 0.1 microgram INH/ml), suggesting at least a bacteriostatic potential of the INH present. However, in vitro studies showed that these urinary concentrations of INH did not kill BCG organisms effectively, even at a concentration of 150 micrograms/ml for 24 h. After the fifth and sixth BCG instillations a significant increase in the concentration of cytokines (IL2, IL6, IL8 and TNFa), IgG and IgA antibodies to BCG and the number of leukocytes in urine was observed. The leukocytes mainly consisted of granulocytes, besides monocytes/macrophages and, in lower amounts, T- and B-lymphocytes and natural killer (NK) cells. The absolute number of granulocytes and the concentration of IgG antibodies after BCG instillation were significantly suppressed by INH, whereas INH appeared to have no effect on the urinary cytokine and IgA antibody concentrations or the total number and phenotype of the leukocytes present. In conclusion, the results of this study indicate that INH does not impair the local immunological stimulation after BCG instillation in man as severely as was observed in the guinea pig and it may be expected that INH does not impair the antitumor efficacy of BCG. PMID- 7992466 TI - Oligonucleotide (GTG)5 in bacterial DNA fingerprinting. AB - On a set of 198 bacterial strains out of 19 different species we have tested the ability of oligonucleotide (GTG)5 to provide definitive DNA fingerprints. All the tested bacteria gave rise to at least one band after digestion with Hinf I and hybridization with radioabelled oligonucleotide (GTG)5. The number of resulting bands varied considerably from species to species and correlated strongly with the GC content of individual bacterial species. A set of 13 well defined laboratory strains of Escherichia coli was divided into 3 groups after GTG fingerprinting, while standard ribotyping revealed no differences. GTG fingerprinting is simple and reliable method for typing bacteria and may be of particular value in those bacterial species, where no other typing systems are available. PMID- 7992467 TI - [Testosterone levels in testicular and epididymal tissue during histopathologic changes in the testes in bulls]. AB - A total of 42 sexual organs of bulls were used to study the relationship between the level of testosterone and the effect of histopathological changes. Genital organs were obtained immediately after slaughter at the Brno abbatoir. Bulls were 14 to 20 months of age and weighed 450 to 650 kg, they were of the Czech Pied, Black and White breeds and their crossbreds. After an assessment of testosterone contents in testicular and epididymal tissues and microscopic examination of organs the concentration of testosterone determined according to the histopathological findings were (Tab. I) as follows. The mean content of testosterone in testicular homogenates was 38.96 +/- 47.0 ng/g. The values for the head, corpus and cauda regions of the epididymal tissue were 5.7 +/- 4.7, 5.3 +/- 5.1 and 3.2 +/- 3.5 ng/g tissue, respectively. The mean level of testosterone in testicular homogenates in the group without histopathological changes of the spermatogenic epithelium was 9.2 +/- 6.77; 5.26 +/- 4.2. In this group the concentration of 5.3 +/- 4.2 from the head 5.4 +/- 5.3 from the corpus and 3.23 +/- 3.26 ng/g tissue were revealed in the cauda of the epididymis. In the group with oedematous infiltration of the interstitium the mean level of testosterone in testicular tissue was determined 16.2 +/- 24.6, in the head of the epididymis it was 6.2 +/- 3.59, in the corpus 4.6 +/- 3.3 and 2.07 +/- 1.2 ng/g of testosterone was obtained from the cauda of the epididymis.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7992469 TI - [Melanoblastoma in laboratory minipigs: a model for studying human malignant melanoma]. AB - Human malignant melanoma is a progressively growing tumour mostly with a fatal prognosis during short time. Its frequency has doubled in some states of the USA during the last few years. Surgical treatment, which is still generally used, has very low efficiency due to the numerous metastases in different organs. An animal model is a necessary prerequisite to develop a new therapy methods. We have recorded primary cutaneous malignant melanomas as well as extensive metastases in the visceral organs in darkly pigmented laboratory minipigs. The primary skin tumours were mostly multiple and they showed a tuberous nodular form. The regular occurrence of tumours in a progeny of three specific mating types suggests the existence of genetic predisposition to malignant transformation. We discuss the use of this animal model for further studies and treatment of human malignant melanoma by our ischemization technique developed previously. PMID- 7992468 TI - [The immunogenicity of a vaccine against enzootic abortion in sheep]. AB - Immunogenicity of vaccine against enzootic abortion of ewes (EPO) was evaluated in sheep and laboratory white mice. The vaccine contained purified and formalin inactivated corpuscules of Chlamydia psittaci. Experiment was performed on ten sheep, Slovak Merino breed, which were negative before vaccination in serological assays and blastic transformation of lymphocytes (BTL) tests. The animals were immunized subcutaneously with 2 ml of vaccine which contained 100 micrograms (sheep No. 1-4) and 20 micrograms (sheep No. 5-8) corpuscules of C. psittaci. Control group (No. 9-10) received the same volume of physiological saline. The second dose of vaccine was given one month after the first dose (No. 1-2--100 micrograms each, and No. 5-6--20 micrograms each). Blood for serological evaluation and BTL test was taken before vaccination and 1, 3, and 6 months after vaccination. The sheep which were given the second dose of vaccine were also evaluated two weeks thereafter. Antibody response in complement fixation reaction (CFR) and enzyme-linked immunosorbent assay (ELISA) was compared with the results of BTL. While the antibody response evaluated by CFR was sporadically positive after administration of the higher dose of vaccine only, in ELISA all sera were positive except one lower dose of vaccine (Tab. I). In all post-vaccination intervals positivity was confirmed by BTL test irrespective of the size and number of vaccine dose (Tab. II). Immunization of mice with one dose (100 micrograms) of vaccine significantly but not completely reduced multiplication of C. psittaci in the lungs of mice (Tab. III). PMID- 7992470 TI - [Changes in hydration in chicken and duck eggs during incubation]. AB - Water loss was determined during incubation in 80 eggs of the domestic fowl, White Leghorn-LB and New Hampshire-NH (between the 1st and 20th day), and in 80 eggs of Beijing White ducks (between the 1st and 25th day). Our data have shown that, the lowest actual water content was found in NH eggs, the highest in the duck eggs. Water content decreased absolutely and relatively during incubation; 365 in LB, 500 in NH and 312 mg/d in ducks. Water loss was higher in the first half of hatching. In the second half it was probably partly offset by water originating from fats oxidized for energetic purposes; the offset made a third in LB and NH, and still more in the ducks. Our results are somewhat different from the literature data, the variability of which is considered to be rather high in general. There were large shifts of water among the egg components during incubation. Water totally disappeared from the albumen, although it contained approximately three quarters of water was at the beginning of hatching. Already in the first half of incubation, more than a third of water was transported to the embryo, fetal membranes and fluids. In the subsequent ten days, water accumulation in the body of the developing and growing embryo was especially rapid; the water amount increased eight times in the fowl, seven times in the duck bodies. Water losses and its shifts show not only interspecific differences related to different lengths of incubation, but also intraspecific ones, between BL and NH. PMID- 7992471 TI - [Epizootiology and pathogenesis of avian mycobacteriosis in domestic pigeons (Columba livia f. domestica)]. AB - The occurrence and expansion of avian mycobacteriosis in the pigeon, its sensitivity to infection and epizootological importance as a source of M. avium were investigated. A total of 470 pigeons were examined coming from seven localities with different epizootological situation in avian tuberculosis. Tuberculous lesions were found out in 2 birds (0.43%) and mycobacteria were isolated from five birds (1.06%). Four out of the five isolated strains of mycobacteria were pathogenic to the domestic fowl. Experimental infections demonstrated the pigeon's high resistance to M. avium. Intramuscular infection with the suspension of M. avium induced histological lesions in the muscle at the spot of puncture in a fortnight, in the liver it was in 28 days, in the lungs and intestines in 56 days. Macroscopic changes were observed at the spot of puncture only in 21 days, but they were not observed in other organs and tissues. The mycobacteria were isolated since the 12th day after infection, particularly from the muscle at the spot of puncture, from liver, spleen and medulla. Macroscopic changes were found out in the intestine in 160 days after peroral infection with feed contaminated with the liver of tuberculous fowl. The mycobacteria of various organs and tissues were isolated from the pigeons killed in 160 days. After a contact with the tuberculous fowl histological changes in the intestinal wall were observed in 380 days in one case only and the mycobacteria were demonstrated by cultivation in the medulla of a pigeon which died in 68 days. PMID- 7992472 TI - [Dr. Jan Vlcek, DVM--his life and work]. PMID- 7992473 TI - Eradication of caseous lymphadenitis in sheep with the help of a newly developed ELISA technique. AB - The purpose of the study was to attempt to eradicate caseous lymphadenitis in sheep with the help of serological monitoring. A newly developed double-antibody sandwich ELISA and the culling of positive or doubtful reactors was the basis of the disease control regimen. Seropositive pregnant ewes were kept in quarantine and removed after lambing; their lambs were artificially fed and allowed to remain in the herd. Under this regimen, supplemented by a number of hygienic measures, caseous lymphadenitis was eradicated from two large flocks of sheep in which the disease was endemic. PMID- 7992474 TI - Antiviral studies of feline infectious peritonitis virus in vitro. AB - Sixteen compounds were tested for their ability to inhibit the replication in vitro of feline infectious peritonitis virus (FIPV), a coronavirus that causes a lethal, immunologically mediated illness in domestic and exotic cats. Six of the compounds, when incubated with cells and titrations of the virus, were found to reduce the virus titres by 0.401 to 0.833 log10 (P < 0.05), using the cytopathic effect as endpoint. Further inhibition studies were performed to determine the 50 per cent effective dose (ED50) levels for these six compounds. Selectivity indices (50 per cent cytotoxic dose [CD50]/ED50) provided the following order of antiviral activity: pyrazofuin > 6-azauridine > 3-deazaguanosine > hygromycin B > fusidic acid > dipyridamole. Compounds which had no statistically significant effect on FIPV in the same assay were caffeic acid, carbodine, 3-deazauridine, 5 fluoroorotic acid, 5-fluorouracil, D(+)glucosamine, indomethacin, D penicillamine, rhodamine and taurine. PMID- 7992475 TI - Naturally occurring tetracycline-like fluorescence in sections of femur from jackals in Zimbabwe. AB - In assessing the potential of the tetracycline compounds as biomarkers in oral rabies vaccination campaigns in jackals in Zimbabwe, the natural prevalence of fluorescent compounds in bone tissue from jackals was investigated. Femur samples were taken from unbaited jackals received for routine rabies diagnosis, and thin undecalcified sections were cut and viewed under an ultraviolet microscope. Of 131 femur samples examined, 49 (37 per cent) had fluorescent markings indistinguishable from those of tetracycline. The result implies that the tetracycline compounds, which are commonly used in rabies baiting campaigns in Europe and North America, cannot be used as biomarkers in jackals in Zimbabwe. PMID- 7992476 TI - Ataxia due to a vertebral haemangiosarcoma in a horse. AB - A haemangiosarcoma in a horse resulted in ataxia affecting all four legs, a low head carriage and a reluctance to flex the neck. Ancillary diagnostic procedures included the analysis of cerebrospinal fluid, standing lateral cervical radiographs and a myelogram. Post mortem a tumour was found which involved the body of the second cervical vertebra and the associated hypaxial muscles, with secondary intravertebral extradural infiltration and focal compressive myelopathy. A histological examination showed that the tumour was a haemangiosarcoma. PMID- 7992477 TI - Atypical Aeromonas salmonicida isolated from ulcerated chub Leuciscus cephalis. PMID- 7992478 TI - A simplified procedure for making reconstituted blastocysts for interspecific and intergeneric transfer. PMID- 7992479 TI - Evaluation of post mortem magnesium concentration in bovine eye fluids as a diagnostic aid for hypomagnesaemic tetany. PMID- 7992480 TI - Dandy-Walker malformation in lambs. PMID- 7992481 TI - Development of the National Home and Hospice Care Survey. Series 1: programs and collection procedures. AB - The National Home and Hospice Care Survey began operation in 1992. This report presents the development of the survey instruments and survey procedures from a feasibility study in 1990 to the first year of operation of the National Survey. PMID- 7992482 TI - Lessons from the Swedish health care system. PMID- 7992483 TI - West Virginia physicians: cardiovascular risk factors, lifestyles and prescribing habits. AB - Physicians educate their patients by direct teaching and by serving as a role model. Through the use of questionnaires, we evaluated the degree to which physicians in West Virginia participate in these activities. Thirty-five percent of the 2,404 licensed physicians in the state returned completed questionnaires. Although 90% prescribed appropriate diets and recommended exercise for their patients, the physicians who responded were often less likely to follow their own advice. Twenty percent of the male physicians and 13% of the female doctors were obese; 30% had LDL cholesterol levels over 130 mg./dl.; 13% had HDL cholesterol values of less than 35 mg./dl.; and 8% had triglycerides over 250 mg./dl. Participation in regular exercise (30 minutes three times per week) was reported by 48% of the male physicians and 47% of the female physicians. Eight percent of the men were smokers, as were 1.9% of the females. These results suggest that the role model aspect of patient education may need to be improved among some West Virginia physicians. It is an inexpensive method of directing attention to lifestyle in order to decrease preventable disorders such as coronary artery disease, obesity, diabetes, and hypertension. PMID- 7992484 TI - A study of Helicobacter-pylori in 100 pediatric patients from the Tri-State area. AB - Helicobacter pylori (HP) is a newly discovered pathogen implicated in the pathophysiology of peptic ulcer disease. The aim of this study was to review all pediatric patients who were evaluated by upper endoscopy through the Pediatric Gastroenterology Service at the Marshall University School of Medicine between July 1990 and March 1993. A total of 100 charts were retrospectively reviewed. HP was diagnosed by CLO-test and confirmed histologically. Results showed that the major presenting symptom was abdominal pain (53%). GI mucosal inflammation was found in 77 patients, and 41% of these cases were associated with HP. Two patients had duodenal ulcer; both were HP+. The incidence of gastritis was significantly higher in patients with HP+ compared to HP-. Follow-up on the HP associated gastritis showed no significant difference in their clinical response irrespective to the treatment, we conclude that HP in children is highly associated with gastritis, but not duodenitis or esophagitis; and in our experience, that CLO has a high failure rate in identifying HP in the mucosa. PMID- 7992485 TI - A combined internal medicine-psychiatry clinic at a community hospital: initial experiences. AB - A new internal medicine/psychiatry outpatient clinic was recently established at Charleston Area Medical Center (CAMC). This report describes the clinical profiles of the first 52 patients and also reviews the clinic's staffing, facilities, referral sources and reimbursement. For large community hospitals, a med-psych clinic may be a useful method of providing psychiatric treatment to medically-ill outpatients. PMID- 7992486 TI - The legal responsibility of physicians supervising physician assistants is significant. PMID- 7992487 TI - The United States women's health research agenda analysis and critique. AB - This article describes the process used to develop a United States women's health research agenda and the published critiques of that agenda. Consideration of methods to develop knowledge about women's health from a feminist standpoint raises questions about the process and products of research that can have emancipatory ends for women. PMID- 7992488 TI - Feminist empiricism as a method for inquiry in nursing. AB - Feminist empiricism may provide a valuable approach for the acquisition, evaluation, and integration of biological knowledge in nursing epistemologies. This article discusses feminist empiricism as a method for inquiry in nursing. Proponents of feminist empiricism strive to work within the current political, social, and scientific structures while acknowledging that all three of these structures must change if less distorted epistemologies are to emerge. Hypertension in women is used to illustrate how feminist empiricism could be used to modify the traditional scientific approach. The argument is made that the androcentricism of the traditional scientific approach must be changed in order to include the problematics of women. Moreover, women must have a central role in determining the problematics of both health and illness in women. A philosophical stance embracing holism cannot deny biological phenomena or preclude research on these phenomena. Theorists and scientists in nursing have a unique opportunity to reconceptualize biological phenomena, from a holistic perspective, in the development of epistemologies for nursing. An argument for the use of basic research as a quantitative methodology, from a feminist perspective, is made. The appropriateness, for nursing, of basic research methodologies to generate knowledge about biological processes, which are within nursing's scientific domain, are discussed. PMID- 7992489 TI - A Black feminist approach to nursing research. AB - Despite the presence of a body of Black feminist literature, the growing body of nursing literature on feminism and the feminist approach to research remains narrowly focused on White feminist concerns. By essentially ignoring the realities of Black women, nursing has reproduced the errors of previous White feminists. This article demonstrates the relevance of the Black feminist approach to nursing by applying it in combination with general feminist research principles and anthropological theory in research concerned with low-income Black women's experiences with dysphoria and depression. The findings of the research suggest that a combination approach more clearly illuminates how context effects dysphoria in poor Black women. PMID- 7992490 TI - Risks and benefits associated with hormonal and surgical therapies for healthy midlife women. AB - The view that menopause is a disease is dominant in Westernized societies, where menopause has long been considered an estrogen deficiency disease and, more recently, an endocrinopathy. The definition of menopause as disease has its origins in patriarchal views and beliefs about women as defective and imperfect, likened to machines that continually need to be fixed. This view of menopause has overshadowed the concept of menopause as a normal biological event, resulting in increased pressure to prescribe steroid sex hormones and perform surgical interventions on healthy women to prevent disease. Institutionalization of the "menopause as disease" ideology has legitimated, and thus condoned, the use of risk/benefit criteria normally used to assess risks versus harms in sick people. The use of these criteria assumes that acceptable risks for the sick are acceptable risks for healthy, well women. PMID- 7992491 TI - A biomedical and feminist perspective on women's experiences with weight management. AB - Weight concerns and dieting have become so normative for U.S. women that weight is the lens through which experience is viewed. The obsession with weight and dieting among women is considered by feminists to be one result of the oppression by women resulting from questionable weight standards and weight control programs that foster a view of overweight as a sign of addiction and lack of control. Feminist critique is used to deconstruct both the literature related to weight standards and health and the research on weight loss/weight management. Feminist and ethnographic methods are used to describe successful and unsuccessful experiences with weight management of 20 Euro-American women who had participated in a 1985 weight study and agreed to be reinterviewed. Success at weight management was examined from a biomedical perspective using Body Mass Index (BMI) norms and from a feminist perspective using participants' subjective definitions of success. Based upon BMI, only 8 members of the study group were defined as successful, whereas based upon the women's perspectives, 11 members were successful. Participants' definitions of successful weight management were divergent from biomedical definitions and could be categorized into three perspectives: biomedical, reframed normal weight, and holistic. Women who ascribed to the biomedical definition of success embodied the cultural ideal of thinness by adhering to an underweight weight norm. Participants using the reframed normal weight definition of success rejected biomedical weight norms and created their own weight norms. The holistic perspective on success involved the use of a broader, health-focused definition of successful weight management and offers some directions for revising current health promotion care relative to weight. PMID- 7992492 TI - The self, health, and depression in elderly women. AB - A short-term, longitudinal, survey study was conducted to examine relationships among actual and ideal self conceptions, physical health, and depression in 149 community-dwelling elderly women. Two theoretical perspectives regarding the self were compared, women's self-development and lifespan developmental theory. As predicted by theories of women's development, relationships with other emerged as a salient aspect of the self in elderly women. Regression analyses indicated that actual and ideal self-conceptions were predicted by depression, but not generally by physical health status. Thus, physical health problems were not global in their effects on the various dimensions of the self in elderly women, but depression was. PMID- 7992494 TI - A feminist approach to concept analysis. AB - Concept analysis is an important device for clarifying the meaning of concepts and the foundations of nursing theory, research, and practice. Exploration of traditional approaches to concept analysis reveals the limitations of these methods for contextual analysis that acknowledges the social construction of the concept and acknowledges gender, class, and racial bias. Concept analysis conducted from a feminist perspective overcomes these weaknesses and becomes a powerful tool for the development of nursing knowledge. PMID- 7992493 TI - The experiences of lesbians in Alcoholics Anonymous. AB - A feminist ethnographic study of lesbians' experiences in recovery from alcohol problems was done to understand from their perspectives how they identified alcohol use as problematic, sought help, experienced health care interactions and participation in Alcoholics Anonymous (AA), and maintained recovery. Through community-based purposive sampling in San Francisco, 35 lesbians recovering from alcohol problems participated in semistructured ethnographic interviews of 2 hours duration, which were subsequently interpreted using ethnographic coding, narrative analysis, and matrix analysis. A major finding was that participation in AA was fraught with tension in three areas. Each tension was defined by two poles of experience that appear to be in conflict. They were assimilation versus differentiation, authority versus autonomy, and false consciousness versus politicization. These tensions are elaborated and supported by examples from the women's interviews. Nursing implications regarding the role of AA in recovery for marginalized women are discussed. PMID- 7992495 TI - [Breast cancer in the man: a report of 30 patients]. AB - A retrospective review of male patients suffering from breast cancer seen over an 18-year period was carried out at the Department of Clinical Oncology of the University Hospital of Graz. Thirty evaluable cases were analysed. Eight patients had Stage I, 11 had Stage II, 8 had Stage III, and 3 had Stage IV disease. Local control was achieved in the majority, 29/30 (97%), by either surgery alone or combined surgery and radiation therapy. Local recurrence developed in 2 (7%) patients. Further 7 (23%) patients developed distant metastases and were treated in accordance with policies developed for the appropriate stage of the disease in females, with hormonal manipulation for hormone receptor-positive and -unknown patients and chemotherapy for hormone receptor-negative patients. The corrected five-year survival (Kaplan-Meier) is 83% for the entire group, 100% for patients with Stage I disease, 86% in Stage II, and 67% in Stage III and IV disease, respectively. This corresponds well with the results in recently published series. Stage of disease at initial presentation was a significant factor determining survival in our investigation. Our own data as well as recent data from literature suggest that with respect to TNM Stages in mammary carcinoma, there is no prognostic difference between men and women. To what extent improved local control by adequate local therapy or systemic adjuvant treatment modalities may improve overall survival remains to be discussed. PMID- 7992496 TI - [Emergency postpartum hysterectomy. A study over 5 years]. AB - A retrospective review was conducted of 34 women who underwent emergency peripartum hysterectomy at Hutzel Hospital--Wayne State University, Detroit from January 1986 to December 1991. Indications for hysterectomy were placenta accreta, uterine rupture, uterine atony and unspecified uterine bleeding. The median age of the patients was 33 years (20-40 years). The median hospital stay was 6 days (4-26 days) and median blood loss was 2000 ml (1000-6000 ml), with a median blood replacement of 4 units of packed cells (0-16 RPC). Postoperative complications included urinary tract infection (2), vaginal cuff cellulitis (3), wound infections (2), septic thrombophlebitis (2), acute tubular necrosis (1) and wound hematoma (1). No patient died. PMID- 7992497 TI - [Magnetic resonance tomography (MRT) of the breast in problem patients]. AB - Over the past few years MRI has become important in the evaluation of inconclusive mammograms. These studies were performed on high-field strength machines, which have the disadvantage of limited accessibility. We evaluated 185 investigations on 169 patients on a 0.5 Tesla MR machine using a dynamic sequence and gadolinium (Gd) DTPA. The results in 107 patients were correlated with the histological findings and MRI assessment proved correct in 44 of 47 benign lesions (93.6%) and 57 of 60 malignant lesions (95%). The 3 false positive results occurred in patients with mastitis, fibroadenoma and an ectatic vessel, respectively. Of the 3 false negative results 2 occurred in patients with microcarcinomas and were due to partial-volume artefacts, whilst the third was due to a technical error. These results compare with those reported in the literature using mainly high-field strength machines. Furthermore, unsuspected second tumours were diagnosed in the ipsilateral breast of 6 women and infiltration of the adjacent thoracic wall in 4 women, findings which had not been evident on mammography. Hence, our results indicate that a mild-field strength MR machine is a valuable tool not only for the non-invasive differentiation between benign and malignant lesions of the breast, but also for planning therapeutic strategy. PMID- 7992498 TI - [Measuring cesium 137 concentrations in surgical specimen of gynecologic tumors and breast milk, amniotic fluid and in umbilical cords, 6 years after Chernobyl]. AB - In the present study, the cesium 137 content in various human tissues was examined 6 years after the Chernobyl reactor catastrophe. The measurements were performed with a gamma-ray spectrometer by means of a germanium/lithium detector. The median of cesium 137 was 20 mBq/ml in mother's milk, 60 mBq/ml in amniotic fluid, 105 mBq/g in umbilical cords, 51 mBq/g in ovarian tumours, and 140 mBq/g in mammary carcinomas. These values lay far below the permissible limit values of 528 mBq/ml or 528 mBq/g for persons not exposed to radiation. The problems of determining the upper limit were also discussed, and it was ascertained that despite the favorably low values recorded in this study a residual risk to health cannot be absolutely precluded in the light of present-day knowledge. PMID- 7992499 TI - [Follow-up results of complications in tibial intramedullary and interlocking nailing]. AB - Faults in the technique of tibial nail locking and possibilities of complications thereafter are numerous, showing that this procedure is also not foolproof. On the basis of the results of follow-up examinations carried out in 42 cases with perioperative and postoperative complications out of a total of 229 patients on whom tibia nail locking was performed in the period from 1987 through 1992, we were able to state that in the learning curve for the initial period the overall rate of complications amounted to as much as 25.5%. After we-like other authors- made routine use of the method of static nail locking the overall rate of complications dropped to 5.6%. Although we cannot confirm an increase in the occurrence of the compartment syndrome on account of static nail locking, we deem it advisable to point to the possibility of this postoperative complications, as well as to the chance of avoiding incomplete healing by early decompression. PMID- 7992500 TI - [Resection of cervical glands in pelviscopic hysterectomy]. AB - A case of pelviscopic hysterectomy with uterine hyperflexion and cervical elongation is presented. In this case we were forced to extirpate the cervical fascia because of uterine hemorrhage by laparotomy after the cervical tissue punch had been performed. The histological findings were supravaginal cervical glands. Complete removal of cervical glandular tissue may be undetermined by hyperflected uteri and cervical elongation. PMID- 7992501 TI - Functional expression of human poly(ADP-ribose) polymerase in Schizosaccharomyces pombe results in mitotic delay at G1, increased mutation rate, and sensitization to radiation. AB - The activity of poly(ADP-ribose) polymerase (PADPRP), a chromatin-associated enzyme present in most eukaryotic cells, is stimulated by DNA strand breaks, suggesting a role for the enzyme in the cellular response to DNA damage. However, the primary function of PADPRP remains unknown. We have selected Schizosaccharomyces pombe as a simple eukaryotic system in which to study PADPRP function because this fission yeast shares with mammalian cells important cellular features possibly associated with poly-(ADP-ribos)ylation pathways. We investigated the existence of an endogenous yeast PADPRP by DNA and RNA hybridization to mammalian probes under low-stringency conditions and by PADPRP activity assays. Our data indicate that fission yeasts are naturally devoid of PADPRP. We therefore isolated S. pombe strains expressing PADPRP by transformation with a human full-length PADPRP cDNA under the control of the SV40 early promoter. The human PADPRP construct was transcribed and translated in S. pombe, generating a major transcript of the same size (3.7 kb) as that detected in mammalian cells and a 113-kDa polypeptide, identical in size to the native human PADPRP protein. Yeast recombinant PADPRP was enzymatically active and was recognized by antibodies to human PADPRP. S. pombe cells expressing PADPRP (SPT strains) showed a stable phenotype that was characterized by: (i) cell cycle retardation as a result of a specific delay at the G1 phase, (ii) decreased cell viability in stationary cultures, (iii) enhanced rates of spontaneous and radiation-induced ade6-ade7 mutations, and (iv) increased sensitivity to radiation. SPT strains may prove efficient tools with which to investigate PADPRP functions in eukaryotic cells. PMID- 7992503 TI - Phosphoribosylpyrophosphate synthetase (PRS): a new gene family in Saccharomyces cerevisiae. AB - Saccharomyces cerevisiae contains at least four PRS genes, all of which have been cloned and sequenced. Each of the four derived amino acid sequences have more than 60% similarity to the corresponding polypeptides of man, rat, Escherichia coli and Salmonella typhimurium. The PRS1 gene maps on chromosome XI, PRS2 on chromosome V, PRS3 on chromosome VIII and PRS4 on chromosome II. One member of this gene family, PRS1, contains a region of non-homology (NHR) shown by cDNA cloning and sequencing not to be an intron. The results presented here suggest that the presence of this NHR is not detrimental to the function of the gene. To date the possibility of protein splicing can be neither proven nor disputed. PMID- 7992502 TI - A new approach for isolating cell wall mutants in Saccharomyces cerevisiae by screening for hypersensitivity to calcofluor white. AB - To study cell wall assembly, a simple screening method was devised for isolating cell wall mutants. Mutagenized cells were screened for hypersensitivity to Calcofluor White, which interferes with cell wall assembly. The rationale is that Calcofluor White amplifies the effect of cell wall mutations. As a result, the cells stop growing at lower concentrations of Calcofluor White than cells with normal cell wall. In this way, 63 Calcofluor White-hypersensitive (cwh), monogenic mutants were obtained, ordered into 53 complementation groups. The mannose/glucose ratios of the mutant cell walls varied from 0.15 to 3.95, while wild-type cell walls contained about equal amounts of mannose and glucose. This indicates that both low-mannose and low-glucose cell wall mutants had been obtained. Further characterization showed the presence of three low-mannose cell wall mutants with a mnn9-like phenotype, affected, however, in different genes. In addition, four new killer-resistant (kre) mutants were found, which are presumably affected in the synthesis of beta 1,6-glucan. Most low-glucose cell wall mutants were not killer resistant, indicating that they might be defective in the synthesis of beta 1,3-glucan. Eleven cwh mutants were found to be hypersensitive to papulacandin B, which is known to interfere with beta 1,3 glucan synthesis, and four cwh mutants were temperature-sensitive and lysed at the restrictive temperature. Finally, nine cwh mutants were hypersensitive to caffeine, suggesting that these were affected in signal transduction related to cell wall assembly. PMID- 7992504 TI - Codon usage table for Schizosaccharomyces pombe. PMID- 7992505 TI - Activation of trehalase during growth induction by nitrogen sources in the yeast Saccharomyces cerevisiae depends on the free catalytic subunits of cAMP-dependent protein kinase, but not on functional Ras proteins. AB - Addition of a nitrogen-source to glucose-repressed, nitrogen-starved G0 cells of the yeast Saccharomyces cerevisiae in the presence of a fermentable carbon source induces growth and causes within a few minutes a five-fold, protein-synthesis independent increase in the activity of trehalase. Nitrogen-activated trehalase could be deactivated in vitro by alkaline phosphatase treatment, supporting the idea that the activation is triggered by phosphorylation. Yeast strains containing only one of the three TPK genes (which encode the catalytic subunit of cAMP-dependent protein kinase) showed different degrees of nitrogen-induced trehalase activation. The order of effectiveness was different from that previously reported for glucose-induced activation of trehalase in glucose depressed yeast cells. Further reduction of TPK-encoded catalytic subunit activity by partially inactivating point mutations in the remaining TPK gene further diminished nitrogen-induced trehalase activation, while deletion of the BCY1 gene (which encodes the regulatory subunit) in the same strains resulted in an increase in the extent of activation. Deletion of the RAS genes in such a tpkw1 bcy1 strain had no effect. These results are consistent with mediation of nitrogen-induced trehalase activation by the free catalytic subunits alone. They support our previous conclusion that cAMP does not act as second messenger in this nitrogen-induced activation process and our suggestion that a novel nitrogen induced signaling pathway integrates with the cAMP pathway at the level of the free catalytic subunits of protein kinase A. Western blot experiments showed that the differences in the extent of trehalase activation were not due to differences in trehalase expression. On the other hand, we cannot completely exclude that protein kinase A influences the nitrogen-induced activation mechanism itself rather than acting directly on trehalase. However, any such alternative explanation requires the existence of an additional, yet unknown, mechanism for activation of trehalase besides the well-established regulation by protein kinase A. PMID- 7992506 TI - Predominant localization of non-specific lipid-transfer protein of the yeast Candida tropicalis in the matrix of peroxisomes. AB - PXP-18 is a 14-kDa major peroxisomal protein of the yeast Candida tropicalis and a homologue of the non-specific lipid-transfer protein (nsLTP) of mammals. Mammalian nsLTP is thought to facilitate the contact of membranes, to stimulate lipid-transfer between them. If PXP-18 functions like nsLTP, it must be present on organelle membranes. Immunoelectron microscopy of C. tropicalis cells indicated that gold particles, which visualized PXP-18, localized exclusively in the matrix of peroxisomes. Subcellular fractionation followed by Western blotting revealed the association of PXP-18 with peroxisomes in C. tropicalis cells. An enzyme-linked immunosorbent assay revealed that almost all the PXP-18 associated with peroxisomes was detectable after the solubilization of the organelle but not before, implying the predominance of PXP-18 inside peroxisomes. This differential assay was applied to the intracellular import of the intact and truncated PXP-18s expressed in Saccharomyces cerevisiae cells. Most of the intact PXP-18 was shown to be imported into the matrix of host-cell peroxisomes, whereas the truncated PXP-18, which lacked the C-terminal tripeptide Pro-Lys-Leu, no longer targeted peroxisomes. These results are consistent with the view that PXP-18 is the matrix protein of peroxisomes and must function in a system other than that of lipid transfer. PMID- 7992507 TI - nmt2 of fission yeast: a second thiamine-repressible gene co-ordinately regulated with nmt1. AB - We previously described a screen for thiamine-repressible genes in Schizosaccharomyces pombe and reported on one such gene, nmt1, required for thiamine biosynthesis. Here we describe a second gene, nmt2, recovered in the same screen. Disruption of nmt2 also resulted in thiamine auxotrophy, indicating a role for the nmt2 gene product in thiamine biosynthesis. Both genes are highly transcribed in minimal medium and repressed in medium containing thiamine, and nuclear 'run-on' experiments confirm that expression in both cases is controlled by the rate of transcription initiation. The virtually identical kinetics of induction and repression suggest that the two genes are co-ordinately regulated. Sequence comparison of the two promoters reveals a canonical TATA box, downstream of which is a perfectly conserved 11 bp element. Transcript mapping experiments show that transcription initiation of both genes is centred on this element. PMID- 7992508 TI - Analysis of beta-glucans and chitin in a Saccharomyces cerevisiae cell wall mutant using high-performance liquid chromatography. AB - We have previously shown that mutations in the yeast KNR4 gene resulted in pleiotropic cell wall defects, including resistance to killer 9 toxin, elevated osmotic sensitivity to SDS and increased resistance to zymolyase, a (1-->3)-beta glucanase. In this report, we further demonstrated that knr4 mutant cells were more permeable to a chromogenic substrate, X-GAL, suggesting that the mutant cell walls were leakier to certain non-permeable molecules. To determine if these defects resulted from structural changes in the cell walls, we analysed the alkali-insoluble cell wall components using HPLC assays developed for this purpose. Comparative analysis using four isogenic strains from a 'knr4 disrupted' tetrad demonstrated that mutant cell walls contained much less (1-->3)-beta glucan and (1-->6)-beta-glucan; however, the level of chitin, a minor cell wall component, was found to be five times higher in the mutant strains compared to the wild-type strains. The data suggested that the knr4 mutant cell walls were dramatically weakened, which may explain the pleiotropic cell wall defects. PMID- 7992509 TI - The two genes encoding yeast ribosomal protein S8 reside on different chromosomes, and are closely linked to the hsp70 stress protein genes SSA3 and SSA4. AB - A 7.4 kb segment of chromosome II was sequenced and analysed. This segment is part of the 25 kb insert of cosmid clone alpha 1004.10 which is located on the left arm of chromosome II. Sequence analysis revealed four open reading frames (ORFs), of which two had been characterized previously (SSA3, AAR2) and one was not identified. The other ORF was precisely 600 bp long and the deduced protein sequence predicted a very basic protein (pI = 11.1; molecular weight = 22.5 kDa). Evidence was found that the ORF is the S40 ribosomal protein gene (RPG) S8. Consensus splice signals were found in the 5' leader sequence and also potential RPG-specific sequences. Chromoblot analysis revealed a second copy of the S8 RPG on chromosome IV or VIII. This copy is also closely linked to an hsp70 protein gene, SSA4. PMID- 7992510 TI - Cloning and characterization of a sulphite-resistance gene of Saccharomyces cerevisiae. AB - In this paper we describe the cloning and sequencing of the gene (SUL1) responsible for sulphite resistance in a Saccharomyces cerevisiae mutant (Casalone et al., 1992). The deduced amino acid sequence predicted that the gene codes for a zinc-finger protein with five fingers. Comparison of wild-type and mutant gene sequences demonstrated that the mutation event was a transversion from C to G; as a consequence of the mutation a histidine substituted an aspartic acid, affecting directly the fourth finger structure. The SUL1 gene sequence corresponds to that of FZF1 gene (Breitwieser et al., 1993) to which no function was attributed. PMID- 7992511 TI - The nucleotide sequence of TTP1, a gene encoding a predicted type II membrane protein. AB - The DNA sequence of a 2967 bp fragment located near the centromere of chromosome II, between the CEN2 and FUR4 genes, was determined. The segment contains a new open reading frame of 1794 bp. The product encoded by the gene, designated TTP1, is a predicted type II membrane protein of 597 amino acid residues with a short cytoplasmic NH2-terminus, a membrane-spanning region and a large COOH-terminal region containing three potential N-glycosylation sites. Gene disruption indicated that TTP1 is not essential for cell growth. PMID- 7992513 TI - Current awareness on yeast. PMID- 7992512 TI - Cloning and DNA sequence of a Kluyveromyces lactis ERD1 homologue. AB - The ERD1 gene product is required for the correct localization of soluble proteins that normally reside in the endoplasmic reticulum (ER). Cell lacking ERD1 secrete resident ER proteins and, in addition, exhibit defects in the processing of glycoproteins. Here, the molecular characterization of the Kluyveromyces lactis ERD1 homologue is described. A comparison of the predicted sequences of the Saccharomyces cerevisiae and K. lactis Erd1 proteins indicates that they are about 30% identical and 50% similar in sequence. Despite low sequence identity, these proteins are predicted to be conserved structurally. Furthermore, the K. lactis protein can functionally complement an S. cerevisiae mutant containing a deletion of the entire ERD1 gene, indicating these two proteins are functional homologues. PMID- 7992515 TI - [Abstracts of the 26th annual meeting of the German Society for Rheumatology. 28 September-1 October 1994, Berlin]. PMID- 7992514 TI - In the budding yeast Kluyveromyces marxianus, adenylate cyclase is regulated by Ras protein(s) in vitro. AB - The presence of adenylate cyclase activity was first demonstrated in membrane fractions from the budding yeast Kluyveromyces marxianus. The enzyme showed a Mn(2+)- and Mg(2+)-dependent activity, with optimal pH at around 6 as observed in other yeast species. As in Saccharomyces cerevisiae, where adenylate cyclase is regulated by RAS1 and RAS2, we detected a guanyl nucleotide-dependent activity. Interestingly Y13-259 monoclonal antibody, raised against mammalian p21Ha-ras, inhibited Mg2+ plus GTP-gamma-S-dependent cAMP production, suggesting that the GTP binding proteins involved in adenylate cyclase regulation could be Ras proteins. The same antibody recognized on Western blot and immunoprecipitated a 40 kDa polypeptide from K. marxianus crude membranes. This polypeptide was not detected by an anti-RAS2 polyclonal antibody raised against S. cerevisiae RAS2 protein, suggesting that Ras proteins from the two species could be structurally different. PMID- 7992516 TI - [A gas chromatographic analysis of the fatty acid composition of Yersinia pestis]. AB - The fatty acid composition of Y. pestis strains, the causative agent of plaque, has been studied. Y. pestis cells have been found to contain great amounts of palmitoleic acid, methylenehexadecanoic acid, oleic acid with elaidic acid, palmitic acid and pentadecanoic acid. Lauric acid, myristic acid, 3-oxymyristic acid and methyleneoctadecanoic acid have been detected in moderate amounts. Vaccine strains, virulent museum and newly isolated strains, while differing in their antigenic structure, have proved to be uniform in their fatty acid composition. In Y. pestis cels, grown on a solid medium for a longer period and at higher temperature, an increased proportion of saturated acids is observed. PMID- 7992517 TI - [The development of a method for isolating and the study of the properties of an extract of the allergens from granary mites]. AB - The method for obtaining allergenic extracts from T. putrescentiae bodies has been developed. As nutrient medium for the cultivation of these mites oat flour has been selected: it has no allergenic cross-reactive properties with T. putrescentiae. Some physico-chemical properties and specific activity of allergenic extracts obtained from these mites were studied. Protein content in these extracts has been found to vary from 0.93 to 0.26 mg/ml, depending on extraction conditions. Protein constitutes 1.5-30.0% of the dry substance of the allergen. After lyophilization the allergen becomes grayish-white powder, readily soluble in water and aqueous saline solutions. In addition, allergenic extracts from T. putrescentiae have pronounced capacity for binding specific IgE antibodies in the sera of patients sensitized to storage mites of this species, which has been confirmed by RAST inhibition and ELISA. Lyophilization produces no changes in the properties and activity of T. putrescentiae allergenic extracts. PMID- 7992518 TI - [A rapid specific reaction of the blood phagocytes to bacteria and the new possibilities for its diagnostic determination in infections]. AB - Materials on the study of specific reaction of phagocytes, rapidly appearing after the contact of the body with soluble microbial substances, are presented. The study has established that of the reaction-inducing stimulus has a non antigenic character and it acts directly on phagocytes. The method for the determination of phagocytic reaction by the ratio of the phagocytosis levels in the specific and control objects has been developed, which makes it possible to use a common diagnostic criterion for different infections and to diagnose them from the onset of the disease. PMID- 7992519 TI - [Pneumocystis pneumonia as an opportunistic infection in AIDS]. PMID- 7992520 TI - [The outlook for creating a single system for the immunoprophylaxis of clostridial wound infections]. PMID- 7992521 TI - [Problems in the general physiology of microorganisms]. PMID- 7992522 TI - [A difficult case in the intravital diagnosis of rabies]. PMID- 7992523 TI - [Meningoencephalitis caused by Yersinia enterocolitica]. PMID- 7992524 TI - [The physicochemical characteristics of a chick embryo hydrolysate-based nutrient broth]. AB - The composition of dried nutrient broth, prepared on the basis of the fermentative hydrolysate of waste chick embryos, has been studied with the use of physicochemical analytical methods. The parameters of total and amino nitrogen, the content of amino acids, peptides, lipids, carbohydrates and microelements have been determined. The qualitative analysis of the peptide composition of the broth has been made. The heterogeneity of peptides with respect to their molecular weights (200--15,000 D and over) has been noted. As regards its physico chemical composition, the broth is a valid medium, suitable for the cultivation of a wide spectrum of microorganisms. PMID- 7992525 TI - [The quantitative composition of lactoflora and a method for its determination]. AB - A newly developed method for the determination of the quantitative composition of lactoflora is described. According to this method, the material under study is subcultured, after its primary inoculation into solid selective medium M P C - 4, placed into fructose- and sorbitol-containing media by the replica method. The characterization of fecal lactoflora of young healthy persons, made with the use of the above-mentioned new method, is presented. PMID- 7992526 TI - [The local manifestations of diphtheria]. AB - The development of diphtheria is characterized by a pronounced local process, but the description of local changes in the disease are based only on postmortem findings. 67 patients with different forms of diphtheria were examined. In 11 cases of descending croup bronchoscopic examination was carried out. As revealed in this study, at the primary stage of the disease films cover the whole of the air duct system, and the process is identical to that on tonsils. In the course of convalescence and under the action of specific antiserum films on the tonsils, the soft palate and the vocal cords disappeared, and films in the larynx, the trachea and bronchi could be easily separated from the mucous membrane, but always with the formation of erosions and even perforations in it. The character of the process was indicative of the absence of any specific action of diphtheria toxin on the mucous membrane at the site of the inoculation of the infective agent. No correlation between the severity of the course of diphtheria, the degree of edema and the frequency of the development of complications was noted. PMID- 7992527 TI - [The intestinal microflora of patients with inflammatory diseases of the maxillofacial area]. AB - The microflora of the large intestine in patients with odontogenic phlegmons of different localization were studied. 80.8% of such patients were found to have microecological disturbances, characterized by a decrease in the number of bacteria belonging to the genera Bifidobacterium, Lactobacillus, Enterococcus and Bacteroides and by an increase in the number of opportunistic microorganisms. PMID- 7992528 TI - [The cloning and expression of the phospholipase D gene from Corynebacterium pseudotuberculosis]. AB - In a number of consecutive gene engineering operations a DNA fragment having a size of about 2.8 kb was cloned in Escherichia coli by means of Blue-script II SK+ used as vector. The insert contained pld gene coding the synthesis of phospholipase D, one of the key factors of C. pseudotuberculosis virulence. The stable and active expression of this gene in E.coli was achieved. High phospholipase A activity was accumulated in the periplasmatic space. The molecular weight of the synthesized protein was 31 kD. The product obtained by gene engineering methods was found to possess the biological activity of the natural product: it induced the hemolysis of sheep red blood cells in the presence of equi factor of Rhinococcus equi and inhibited the hemolytic activity of Staphylococcus aureus beta-hemolysin (phospholipase C). The pld gene cloned in these experiments differed from that of another C.pseudotuberculosis strain. Further research is underway with a view of searching for the limits of pls gene. PMID- 7992530 TI - [The purification and characteristics of listeriolysin O from Listeria monocytogenes]. AB - A scheme of the purification of listeriolysin O produced by L. monocytogenes strain NCTC 7973 was developed. The isolation procedure included the cultivation of the bacteria in heart-brain broth, the concentration of culture liquid free of bacteria with ammonium sulfate, cation exchange chromatography on a column packed with CM-Sepharose and Mono S, gel chromatography on a column packed with Superose 12. The preparation obtained with the use of this procedure was homogeneous, as confirmed by the data of SDS electrophoresis. The protein obtained in this investigation was no different from the protein studied earlier in its physico chemical properties (molecular weight, heat stability, inhibition with thiole active compositions, cholesterol, sensitivity to proteolytic enzymes) and corresponded to the characteristics of thiole-dependent hemolysins. PMID- 7992529 TI - [The efficacy of different antimicrobial preparations in treating patients with disseminated peritonitis]. AB - The results of our investigations revealed that in 68% of cases the treatment of patients with diffuse peritonitis with ampiox, gentamicin and metronidazole led to arresting the infectious process and to a considerable decrease in microbial contamination of the abdominal cavity. The use of cephalosporins and metronidazole proved to be effective in 85% of cases. In this treatment a considerable decrease in the amount of aerobic and anaerobic bacteria in peritoneal exudate was registered. In the process of treatment with cyprophloxacin positive clinical and microbiological dynamics were observed in all patients. PMID- 7992531 TI - [The epidemiological characteristics of single cases of campylobacteriosis in urban inhabitants]. AB - The results of the analysis of the epidemic situation in Campylobacter infection and the epidemiological markers of the strains of the infective agent have demonstrated that Campylobacter infection, registered as single cases among the residents of Vologda, has an epidemic character. An intensive and uncontrolled process among fowl (chickens) and the absence of effective measures of specific prophylaxis make it necessary that a system of hygienic measures be given priority in the complex of measures aimed at the prophylaxis of Campylobacter infection. PMID- 7992532 TI - [The prevalence of etiological forms of viral hepatitis in Khabarovsk]. AB - For the first time the etiological structure of viral hepatitis in the Far East, in Khabarovsk, has been studied. The leading etiological form of viral hepatitis is hepatitis A. The spread of hepatitis B and nondifferentiated hepatitis is less than that of hepatitis A. The ratio of different etiological forms of virus hepatitis is determined by the epidemiological situation. At the period of epidemic hepatitis A morbidity increases while hepatitis B morbidity decreases. The occurrence of nondifferentiated hepatitis at different periods of observation remains unchanged. PMID- 7992533 TI - [An evaluation of the allergizing properties of merthiolate as a component of adsorbed DTP vaccine]. AB - The study of the allergenic properties of thimerosal contained in adsorbed DPT vaccine was carried out. Two variants of this vaccine, with and without thimerosal, as well as thimerosal alone (diluted 1:10,000, which corresponds to the content of this preservative in the vaccine), were used in experiments. The phenomenon of anaphylactic shock, passive dermal anaphylaxis and skin tests were used as test-systems. The injection of each of the two variants of the vaccine induced the state of sensitization in guinea pigs. At the same time no differences in the intensity of manifestations of immediate and delayed hypersensitivity induced by preparations with and without thimerosal were registered. The solution of thimerosal alone exhibited no sensitizing properties. PMID- 7992534 TI - [The activity of NK and K cells in mice vaccinated against plague]. AB - The activity of NK and K cells in mice immunized against plague has been studied. This activity has been shown to depend on the dose of the vaccine and the time elapsed after immunization. The booster immunization of mice leads to an increase in the specific sensitization of lymphocytes, the antibody level and to an increase in the activity of killer cells. Changes in the cytotoxicity of NK cells on days 21-28 after primary and booster immunization are considered to occur not due to the action of Yersinia pestis themselves, but as the result of the immunological transformation induced by these microorganisms in the animals. PMID- 7992535 TI - [The protective activity of Yersinia pseudotuberculosis antigens]. AB - Samples of Y.pseudotuberculosis (serovar I) antigens, represent a high-molecular lipopolysaccharide (LPS) fraction with a mol. wt. of 22.5 kD and fractions of outer membrane proteins isolated by the method of M. Osborn and R. Munson (1974), were tested in comparison with the activity with live cells of Y. pseudotuberculosis I attenuated mutant KV 9/2, having lost its Cad plasmid of virulence with a mol. wt. of 47 MD and carrying 2 attenuating markers: resistance to crystal violet and nalidixic acid. In experiments on guinea pigs pathomorphological studies demonstrated high protective activity of Y.pseudotuberculosis I attenuated mutant KV 9/2 and a pronounced protective effect achieved after the immunization of the animals with complex biopolymers, including a high-molecular LPS fraction and outer membrane proteins. PMID- 7992536 TI - [The use of solid-phase immunoenzyme analysis for the diagnosis of a suppurative infection of the maxillofacial area caused by Bacteroides melaninogenicus and Staphylococcus aureus]. AB - In 186 patients with odontogenic infection the level of antibodies to B.melaninogenicus polysaccharide antigen, teichoic acid and S.aureus polysaccharide was determined in the enzyme-linked immunosorbent assay (ELISA). The positive values of ELISA indices were found to coincide with the data of bacteriological study in more than 90% of cases. The role of B.melaninogenicus and S.aureus associations in the development of purulent infections was confirmed with the use of ELISA in 34.2% of the patients for S.aureus and in 50% of the patients for B.melaninogenicus and bacteriologically in 31.4% and 46.9% of the patients respectively. PMID- 7992537 TI - [The problems of a loss of activity of the sorbed ligands in heterogeneous immunoenzyme analysis]. AB - Literature containing a number of data on the problem of the loss of activity of adsorbed ligands in the heterogeneous enzyme immunoassay has been analyzed. This analysis has demonstrated that this process is the superposition of the processes of both denaturation and oxidation of the adsorbed ligand, as well as its desorption from the surface of the plate. The proofs of both denaturation and desorption increments of the process of activity loss are presented. Attempts at the theoretical calculations of desorption components with the use of the concept and parameters of the solubility of plastic and dipeptides have been successfully made. Some ways for decreasing the loss of activity of solid-phase antigens (antibodies) have been outlined. PMID- 7992538 TI - [An evaluation of the effectiveness of laboratory diagnostic methods for brucellosis]. AB - The diagnostic value of bacteriological and serological methods for the laboratory diagnosis of brucellosis was studied. In the analysis of milk and cheese specimens Brucella cultures were isolated and differentiated as B.melitensis, biovar I, and B.abortus, biovar 4. In 25.6% of cases B.melitensis culture, biovar 1, was isolated from the blood of persons suspected for brucellosis. The isolation of B.melitensis culture from milk showed that this infective agent migrated from small animals to cattle, which was indicative of a high risk of human infection in the state of Zacatecas, Mexico. The comparative evaluation of serological diagnostic methods (the agglutination test in test tubes, Huddleson's slide test, the acidic rose bengal test and the 2 mercaptoethanol test) showed high sensitivity of rapid tests (Huddleson's test and the rose bengal test in 93.7% and 87.9% of cases respectively). The 2 mercaptoethanol test which gave positive results in 63.8% of cases provided additional information characterizing the course of infections process. PMID- 7992539 TI - [Europium-labelled Staphylococcus aureus protein A as a reagent for determining specific antibodies]. AB - In this work the conditions of labeling protein A with europium ions were studied and the conjugates obtained in this study were compared with traditional peroxidase conjugates currently used in immunochemistry. The conjugates of protein A with Eu3+ chelate were obtained with the use of cyclic dianhydride of diethylenetriaminepentaacetic acid (DADETPA). Conjugation methods with the use of DADETPA was shown to permit obtaining high-quality conjugates with europium chelates. Europium-labeled protein A ensured the sensitivity of the determination of adsorbed IgG at a level of 2 ng/ml and the dynamic analytical range within 3 1,000 ng/ml, which essentially exceeded similar characteristics of peroxidase conjugates with protein A. Europium-labeled protein A was used for the detection of antibodies to Francisella tularensis in the sera of humans immunized against tularemia. The sensitivity of this assay exceeded that of the enzyme immunoassay 10- to 40-fold. A conclusion was made on the possibility of using europium labelled protein A for the determination of specific antibodies to F.tularensis. This preparation may be useful in the determination of specific antibodies in low immune sera. PMID- 7992540 TI - [Coxiella burnetii antigens--inducers of tumor necrosis factor and interleukin 1]. AB - The cultivation of mouse peritoneal macrophages in the presence of antigenic preparations obtained from C.burnetii was accompanied by the appearance of phagocytes and considerable amounts of tumor necrosis factor and interleukin 1 in the culture medium. The production of cytokines depended on the doses of preparations used as inducers. The special treatment of C.burnetii antigen, selectively removing its phospholipid components, led to a sharp drop in its capacity for stimulating the production of cytokines. PMID- 7992542 TI - [The effect of recombinant interleukin-1 beta on concanavalin A-induced lymphocyte reactions]. AB - As revealed by investigations made by the use of the method of luminol-dependent chemiluminescence and light dispersion, the addition of concanavalin A (ConA) to the suspension of human peripheral blood lymphocytes and subsequent incubation with recombinant interleukin-1 beta leads to a sharp increase in the yield of chemiluminescence and the rate of cell aggregation in comparison with similar parameters obtained for cells, not treated with interleukin-1 beta. The study revealed the potentiating action of recombinant interleukin-1 beta on ConA induced proliferative response of thymocytes in the culture. The mechanisms of the priming action of recombinant interleukin-1 beta on ConA-induced reaction of lymphocytes are discussed. PMID- 7992541 TI - [The reaction of cultured mononuclear cells from the peripheral blood of patients with lepromatous leprosy to rabbit interleukin-1]. AB - Interleukin-1 (IL-1) obtained from leukocytes of rabbit peritoneal exudate was added to concanavalin A-stimulated cultures of peripheral blood mononuclear cells obtained from healthy donors and patients with lepromatous lepra at the active stage of the process. The comitogenic effect of IL-1, observed in the process of its action on mononuclear donor cells, has been found to be linked with the presence of the state of leprous reaction in the patient and is not manifested in the absence of such state. This indicates that intercellular cooperation processes mediated by IL-1 play some role both in the mechanisms of immunodepression in lepra and in the pathogenesis of leprous reactions connected with the activation of cell immunity. PMID- 7992543 TI - [The enterotoxigenic activity of Campylobacter isolates taken in acute intestinal infections in children and its clinical assessment]. AB - The screening of Campylobacter clinical isolates in ELISA with the use of nitrocellulose filters as solid phase has revealed the possibility of the detection of enterotoxins. The capacity for producing thermolabile enterotoxin has been found in 75.9%, Shiga-like enterotoxin in 56.4% and both enterotoxins in 31.3% of the tested C. jejuni and C. coli strains. The influence of the enterotoxigenic capacity of the strains under study on the severity of Campylobacter infection and on its numerous clinical manifestations in children has been established. PMID- 7992544 TI - [The mechanism of the combined action of immunomodulators on phagocytic cells]. AB - The study revealed that the injection of different immunomodulators (salmosan, levamisole, BCG, prodigiosan) or such irritants as meat-peptone broth led to the formation of heterogeneous macrophage populations, differing in their phagocytic function, oxidation metabolism, secretion of protein products. The additional injection of immunomodulators led neither to further increase in the influx of cells into the abdominal cavity, nor to further activation of the phagocytic function in all cases, irrespective of background and additional preparations used in the experiment. The response was determined by the first stimulus. Each of these macrophage populations was seemingly in a characteristic state of self maintenance during a certain period when it was insensitive to the second stimulus, i.e. the existence of a certain refractory period was revealed. The effect produced by the additional injection was registered only at the expiration of the refractory period. Therefore, the data on the presence of a certain refractory period and its duration for each immunomodulator should be established and taken into consideration in working out the schedule of their combined use. PMID- 7992545 TI - [The immunomodulating and metabolic actions of thymalin in an experimental herpetic infection]. AB - In experiments on the intracerebral inoculation of herpes virus, type I, into 38 CBA mice the phagocytic activity of peritoneal exudate, cells, spontaneous migration of leukocytes and their response to phytohemagglutinin (PHA), the activity of key enzymes of gluconeogenesis, lipid peroxidation in liver tissue, as well as the level of glucose and glycosylated hemoglobin in the blood, were determined simultaneously with the histological study of the brain and the main internal organs of the animals, receiving thymalin treatment and not receiving it. As demonstrated in these experiments, the development of experimental infection was accompanied by the inhibition of the phagocytic activity of peritoneal macrophages and response of leukocytes to PHA, as well as metabolic shifts in liver tissue. Treatment with thymalin produced a combined immunomodulating and metabolic effect. PMID- 7992546 TI - [The preventive properties and therapeutic efficacy of an antitetanus immunoglobulin for experimental intravenous administration]. AB - The new preparation of antitetanus immunoglobulin for intravenous injection has been developed at the Kirov Research Institute of Hematology and Blood Transfusion. The technology for obtaining this preparation is based on the method of acidic fermentative hydrolysis. The preparation has high specific potency: one dose contains at least 1,500 I.U. of tetanus antitoxin. As demonstrated in the experimental study of the preparation on mice, its intravenous injection 0.5 hours after challenge completely neutralizes the action of tetanus toxin, its use 24 hours after challenge protects all animals from death, while eliminating the clinical signs of the disease in 50% of them. The intramuscular injection of the preparation has proved to be considerably less effective. PMID- 7992547 TI - [Thymosin alpha-1 and hybrid proteins consisting of tumor necrosis factor-alpha and thymosin alpha-1 enhance the efficacy of vaccination against the causative agent of plague]. AB - The influence of the preparation of chemical thymosin alpha 1 (T), recombinant thymosin alpha 1 (rT), tumor necrosis factor (TNF) and hybrid proteins on their basis (T-TNF, TNF-T and T-TNF-T) on the effectiveness of immunization against Y.pestis have been studied. The preparations of T and hybrid proteins exhibit immunostimulating action, enhancing specific immunity when injected at different periods of the vaccinal process against Y.pestis virulent strain 231 in experiments on mice and guinea pigs. The highest effectiveness and reproducibility of results is observed after the use of hybrid protein T-TNF-T. An increase in immunity after the use of the preparations of hybrid proteins is accompanied by the activation of its T-cell element. The influence of rT on the restoration of the immune system of white mice after their exposure to sublethal doses of gamma radiation has been shown. PMID- 7992548 TI - [The distribution of antibodies to the herpes simplex virus in different types of raw material used for producing immunoglobulin preparations]. AB - The distribution of antibodies to herpes simplex virus (HSV) in different kinds of biological raw materials has been studied with the use of the enzyme-linked immunosorbent assay. The study has revealed that the content of herpes-specific antibodies in pooled placental and donor blood sera and in the preparations of commercial normal immunoglobulins is sufficiently uniform, and 7-10% of these sera and preparations have elevated titers of antibodies to HSV. Blood sera of individual donors are characterized by greater differences in the content of herpes-specific antibodies. About 10% of such sera have significantly greater titers of antibodies to HSV. From selected blood sera of individual donors with initially high titers of antibodies to HSV the preparation of antiherpes immunoglobulin has been obtained; the specific activity of this preparation is 4- to 6-fold higher than that of preparations of commercial normal immunoglobulins. PMID- 7992549 TI - [The immune status of patients with typhoid fever]. AB - The immune status in 48 typhoid fever (TF) patients has been studied. As revealed in this study, during the fever period of the disease pronounced disturbances in immune homeostasis are observed, which are manifested by T lymphopenia, the prevalence of suppressor subpopulations of T lymphocytes with the prevalence of T helpers, a considerable rise in the level of circulating immune complexes (CIC), mainly highly pathogenic medium- and low-molecular complexes. At the early period of convalescence the preservation of all these signs is indicative of fact that the treat of TF relapse is present. IN the prognosis of the disease the most informative signs are a decrease in the number of T lymphocytes and active (early) rosette-forming cells, an increase in the level of CIC and the presence of 75% and more highly pathogenic medium- and low-molecular complexes among them. PMID- 7992551 TI - The effect of amino acids and amino acid derivatives on cell proliferation. AB - The effect of certain amino acids and amino acid derivatives on cell proliferation have been studied in the author's Institute for more than 25 years. The optically active forms of arginine, lysine, aspartic acid and glutamic acid influence the growth of transplantable rat tumors. L-arginine, D-lysine, L aspartic acid and D-glutamic acid promoted; D-aspartic acid, L-glutamic acid, D arginine and L-lysine inhibited tumour growth. E-amino trimethyl-lysine (TML) stimulated cell proliferation in various cell systems (bone marrow, small intestine, cultured lymphocytes). When administered simultaneously with high doses of Cyclophosphamide, Vincristin or Doxorubicin to tumour-bearing mice, TML decreased the toxicity of the antitumour drugs, resulting in a higher rate of survivors. L-leucine methyl ester caused cell death of mouse peritoneal macrophages by inducing disruption of macrophages. PMID- 7992550 TI - [Sorbed animal immunoglobulins--a reserve for increasing the output of therapeutic antitoxic and diagnostic sera]. AB - Conditions for the desorption of immunoglobulins from the surface of blood cells of animals used for the production of antitoxic therapeutic and diagnostic sera have been established. The possibility of obtaining, in principle, additional amounts of immunoglobulins and specific antibodies (in comparison with their initial content in sera) without increasing the number of producer animals has been demonstrated. The possibility of using desorbed immunoglobulins and specific antibodies in the production of therapeutic and diagnostic immunobiological preparations is discussed. PMID- 7992552 TI - Anionic amino acid transport in ras- transformed fibroblasts. AB - The sodium-dependent transport of anionic amino acids is suppressed in NIH3T3 cells that constitutively express ras oncogenes. In a model of NIH3T3 cells in which ras expression is triggered in the presence of dexamethasone, aspartate transport decreases gradually upon dexamethasone treatment and is almost completely suppressed after two days of incubation in the presence of the steroid. In the same cell model, lovastatin, an inhibitor of beta hydroxy-beta methyl-glutaryl-CoA-reductase and, hence, of farnesylation of p21ras, partially protects aspartate transport from the inhibition observed upon steroid treatment. Determinations of cell glutamate in ras-expressing and non expressing cells indicate that in both cell models glutamate decreases when extracellular medium is depleted of glutamine. However, this decrease is much faster in cells expressing ras (either constitutively or conditionally). It is proposed i) that cell production of oncogenic p21ras hinders sodium-dependent transport of anionic amino acids and ii) that the transport alteration impairs the maintenance of cell levels of glutamate in ras-expressing cells. PMID- 7992553 TI - Potential markers (enzymes, proteoglycans) for human liver tumors. AB - In the present work the activities of GGT and G-6-Pase and the content of Cyt P 450 were determined in surgically removed liver specimens (16 hepatocellular carcinomas, 8 focal nodular hyperplasias and 4 adenomas). The activities were compared to the surrounding seemingly normal liver tissue. In the adenomas neither of the enzymes studied showed alterations, characteristic for hepatocarcinogenesis. Four out of 8 FNHs had the enzyme pattern that was found in experimental liver carcinogenesis. Liver carcinoma specimens proved to be heterogenous. Neither elevated GGT nor reduced G-6-Pase activity was consistent in these samples although the average of G-6-Pase activity decreased to 50 percent. Cytochrome P-450 was significantly reduced in the majority of cases, showing the best agreement with the tendency observed in experimental models. As an other approach, the qualitative and quantitative alterations of proteoglycans (PG) were analized in the same tumor samples. The amount of sugar components of PGs the glycosaminoglycans (GAG) increased by many times in liver tumors. Carcinoma samples were characterized by about twentyfold increase in chondroitin sulfate content, compared to normal liver. The enhancement of GAGs is partly the consequence of a selective alteration in PG expression. The amount of perlecan and decorin was found to be increased, while syndecan disappeared from liver carcinomas. These data suggest that malignant transformation in liver is accompanied by specific alteration in the content, composition and structure of PGs. Presumably, these changes have significance in tumor progression and have also the potential to be used as markers for liver tumors. PMID- 7992554 TI - Significance of cellular DNA content in human liver tumors. AB - The nuclear DNA content of 26 liver tumors (1 adenoma, 10 focal nodular hyperplasia and 15 hepatocellular carcinoma) was measured by flow cytometry (FCM) on formalin-fixed, paraffin-embedded tissues. All lesions developed in noncirrhotic liver and were negative for HBsAg. DNA aneuploidy was found in 1/10 FNH (one hypodiploid) and in 11/15 HCC (73%). Intratumoral heterogeneity was observed in three cases. In HCC the ploidy level showed no correlation with tumor size or histopathological grading. Results support the potential of FCM to measure DNA content in archival pathological specimens, and also that DNA content itself has no diagnostic value. PMID- 7992555 TI - Values and limits of combined use of 4 tumor markers (CEA, TPA, NSE and SCC) in un-treated patients with lung cancer. PMID- 7992556 TI - The value of ploidy in the prognosis of the colorectal cancer. AB - Between the prognostic indices in the colorectal cancer the ploidy has determined a great interest. To study the value of ploidy in the prognosis of the colorectal cancer, as a sign of the aggressiveness of the tumor for a therapeutic help, we have examined, in a retrospective study, 150 patients who had a colorectal cancer resected from 1980 to 1986. We have compared ploidy of specimens of paraffin embedded tumors and Dukes' stage, Grading, the over-all, distal and local recurrence and the survival at 5 years. The statistics were performed by the chi square test, the Fisher exact-test and the Wilcoxon test. The aneuploids are 126 (84%) and the diploids 24 (16%). The correlations of ploidy and the Duke's stages, the Grading, and the over-all and local recurrence are not statistical significant. The distal recurrence of the aneuploids and the better survival of the diploids are significant. In conclusion the ploidy is only a generic indicator of the aggressiveness of the tumor, not useful for a more complete therapeutic choice. PMID- 7992557 TI - Endocrine tumors of the pancreas: the pathologist's approach. AB - The introduction of modern cytological techniques has provided the pathologist of tools that considerably improved his analysis of pancreatic endocrine tumors and that are discussed in this review. Hormonal characterization of the tumors by immunohistochemistry significantly contributed to the definition of the current functional classification of the tumors and proved that ectopic tumors (producing extrapancreatic hormones) are as common as entopic tumors synthesizing pancreatic hormones. The identification of neuroendocrine markers and of other active non hormonal substances extended our knowledge on the functional properties of tumor cells often with significant fall out on the biology of the corresponding normal cells. Current studies are mostly oriented toward the analysis of cell proliferation and appear to open promising perspectives for the prognostic evaluation of the tumor course. PMID- 7992558 TI - Bone marrow transplantation in patients with acute leukemia. AB - At least three factors may be responsible for leukemic relapse in patients receiving ABMT: (a) minimal residual disease; (b) leukemic cells reinfused with the graft; and (c) the lack of a graft-versus leukemia effect. Techniques for pharmacological marrow decontamination, clinical result obtained with ABMT and the efficacy of ABMT with mafosfamide purged marrow in patients with acute myelogenous leukemia are reviewed. PMID- 7992559 TI - Lack of correlation between the number of donor nucleated bone marrow cells or CFU-GM content and the rapidity of engraftment in allogeneic BMT. AB - The data of 146 consecutive allogeneic bone marrow transplant patients over a two year period from one center were analysed to study the possible correlation between the rapidity of engraftment and the number of the transplanted nucleated bone marrow cells (TNBMC) or CFU-GM. Thirty-four patients were excluded because of early death, previous splenectomy, colony stimulating factor therapy or non engraftment. Of the remaining 112 patients 85 had both TNBMC and CFU-GM data alone. No correlation was found between the rapidity of engraftment and the number of TNBMC or CFU-GM. PMID- 7992560 TI - Relationship between epidermal growth factor receptor and other prognostic factors in gynecological cancers. AB - In 62 cases of gynecological malignancies, 16 of the ovarian, 31 of the endometrium and 15 of the cervix, the EGF-R status was evaluated in order to establish its prognostic value and its correlation with other classical prognostic factors. We have failed to demonstrate any correlation between EGF-R status and stage, grade and hormonal receptors, ER/PgR, in ovarian and cervical cancer. In contrast, in endometrial cancer, we observed significantly lower levels of EGF-R in poorly differentiated tumors. Moreover, a weak negative relationship between EGF-R and PgR status was found. Regarding survival, we noticed a better prognosis in patients with ovarian cancer EGF-R positive, but without statistical significance. PMID- 7992561 TI - Radical operative treatment of cervical cancer. AB - From July 1990 until the end of December 1993, 86 patients with cervical cancer were treated by radical hysterectomy and lymphadenectomy according to Wertheim, at the I. Department of Obstetrics and Gynecology of Semmelweis University Medical School Budapest. Data analysed according to the histological examination results of their surgical specimens. A good relationship was found to exist between the pathological anatomical stage of the cancer, tumor volume, incidence of lymph node involvement. The authors have combined the conventional surgery of gynecologic malignancies with the use of the CUSA. In the course of few interventions they did not experience any serious intra- or postoperative complications. The results showed that good results with surgical treatment can be achieved even for very large cancers (Stage II B) with a high frequency of lymph node involvement. PMID- 7992562 TI - AIDS and HIV infection in Belgium. PMID- 7992563 TI - [Status of 3 years of hyperthyroidism treatment with iodine 131]. AB - We analysed retrospectively the results obtained during 3 years in the treatment of thyrotoxicosis with 131-iodine. A group of 32 patients, including 21 Graves' diseases, 10 multinodular toxic goitres and 1 toxic adenoma has been collected. The therapeutic efficacy of one dose of radioiodine, assessed after 6 months was 100% in toxic multinodular goitres and 57% in Graves' diseases. No acute complications were observed. The best radiosensitivity of toxic multinodular goitres compared with diffuse goitres is probably due to the mechanisms themselves of thyrotoxicosis in these diseases. Results also suggest that multinodular toxic goitres in our country should be systematically treated with antithyroid drugs before radioiodine. In Graves' disease, no predictive factor of the early response to therapy could be definitely evidenced. Finally, clinicians should be aware of the advantages of such a treatment of thyrotoxicosis which is not very aggressive and at least definitive. PMID- 7992564 TI - [Long-term follow-up of patients with complete congenital auriculo-ventricular block treated with a cardiac stimulator]. AB - The congenital complete heart block (CCHB) is a rare affection. In our two centers, in a period of 10 years, 1405 pacemakers were placed and only 10 (0.71%) for CCHB. We review the clinical history, the EKG's, echocardiography and Holter monitoring of these 10 patients. All of them were symptomatic. After pacemaker implantation, symptoms were improved in 90%. No death or other morbidity were observed during the long-term follow-up. So, the clinical outcome of patients with CCHB who underwent prophylactic pacemaker implantation seems to be associated with an excellent prognosis. PMID- 7992566 TI - Paraquat poisoning. "State of the art". AB - The authors describe the main features of acute paraquat poisoning. The clinical picture together with severity grading is presented. The pathophysiological mechanisms responsible for multiple organ dysfunction are discussed. Despite a better understanding of pathophysiological pathways and numerous experimental data, the treatment of the most severe forms of poisoning remains limited. The efficacy of more recently developed therapeutic approaches is still to be evaluated. PMID- 7992565 TI - [Resistance to chemotherapy: current progress]. AB - Chemotherapy has become a very important part of the therapy for several cancers. Complete remission, and sometime cure, can be achieved with this treatment modality. However, when relapse occur, a second remission is seldom obtained. This failure is believed to be linked, at least in part, to the development of drug resistant tumor cells. Our understanding of the mechanisms underlying this resistance, especially regarding the multidrug resistance (MDR) phenomenon, has improved over the recent years. New strategies are being developed to circumvent drug resistance and come now to clinical trials. PMID- 7992568 TI - Metastatic involvement of the left atrium revealed by electrocardiographic Ta segment change. AB - We describe a case in whom an unusual alteration of the atrial repolarization observed on routine electrocardiogram (Ta segment depression) led to the echocardiographic diagnosis of metastatic involvement of the left atrium by a lung cancer. Electrocardiographic abnormalities in the metastatic involvement of the heart are non specific but observation of new changes may suggest the diagnosis and modify the staging and the treatment. PMID- 7992567 TI - Two AIDS patients with life-threatening pancreatitis successfully treated, one with ganciclovir the other with foscarnet. AB - Two AIDS patients, clinically suspected to have cytomegalovirus (CMV) pancreatitis are described. The first patient was successfully treated with ganciclovir 10 mg/kg/day. This patient refused ganciclovir maintenance treatment and developed 3 other episodes of pancreatitis which responded each time to ganciclovir. The second patient was successfully treated with foscarnet 200 mg/kg/day followed by maintenance foscarnet treatment 100 mg/kg/day. No pancreatitis relapse was observed. PMID- 7992569 TI - Infectious disease surveillance: early warning systems and public health interventions in a Belgian and European perspective. PMID- 7992570 TI - Guidelines for diagnosis and treatment of adult hyperlipidaemias. Consensus of the Belgian Lipid Club. PMID- 7992572 TI - A turning point in breast cancer cytology reporting: moving from callowness to maturity. PMID- 7992573 TI - Special issue: Breast cancer cytology. PMID- 7992571 TI - Penicillin and acute streptococcal pharyngitis. PMID- 7992574 TI - Fine needle aspiration cytology of tubular breast carcinoma and radial scar. AB - Fine needle aspiration cytology (FNAC) findings in 33 tubular breast carcinomas (TC) and 10 radial scars (RS) were reviewed. In 19 (57%) cases of TC, a categorical diagnosis of malignancy could be made. Four (12%) TC, all containing myoepithelial cells, were misdiagnosed as benign. None of the RS was misinterpreted as malignant on FNAC. All RS smears contained myoepithelial cells. Although RS shared some of the cytologic features of TC, the lack of conspicuous nucleoli and pleomorphism prevented a false-positive diagnosis. Tubular angular structures, considered to be a characteristic feature of TC, may also occur in RS. Cellularity was poorer in RS than TC. The FNA yield obtained when attempting to aspirate small TC and RS lesions may originate in adjacent breast lesions and give a misleading cytologic picture. The occurrence of myoepithelial cells and/or lack of dissociation are not unequivocal benign signs in FNA smears; such findings do occur in TC. Finally, the difficulties that may be encountered in the diagnosis of TC and RS by frozen section are briefly discussed. Radiology often helped in establishing a diagnosis of malignancy in TC but did not help in ruling out malignancy in RS. A teamwork approach to the diagnosis and management of these lesions is recommended. PMID- 7992575 TI - Cytologic evaluation of phyllodes tumors as compared to fibroadenomas of the breast. AB - In an attempt to better understand the cytopathologic features of phyllodes tumors (PTs) and to differentiate PTs from fibroadenomas (FAs) of the breast, cytologic smears prepared from 17 and 19 histologically diagnosed cases of PT and FA, respectively, were reviewed. PT cases were histopathologically graded as benign, borderline and malignant. Cytologically, hypercellularity of stromal cells with recognizable cytoplasm was observed in 6 of 7 borderline and malignant PT cases, but none of the benign PT or FA cases revealed such hypercellular stroma. Between all PT and FA cases, no statistically significant differences could be obtained in the nuclear size of stromal cells, folding of epithelial cell sheets or number of foamy macrophages. The study revealed that the abundance of stromal cells with cytoplasm, not naked nuclei, was strongly suggestive of borderline and malignant PT, but the differentiation between benign PT and FA was difficult on the basis of the cytopathologic findings. PMID- 7992576 TI - The spectrum of the "gray zone" in breast cytology. A review of 186 cases of atypical and suspicious cytology. AB - A "gray zone" exists in fine needle aspiration (FNA) cytology of breast; there an unequivocal diagnosis cannot be made. Previous studies have reported a gray zone incidence of 6.9-20%. We reviewed 2,197 fine needle aspirations (FNAs) of the breast performed at our institution to determine the incidence of the gray zone, analyze the sources of difficulty and establish guidelines to minimize the size of the gray zone. One hundred eighty-six (10%) of the total 2,197 FNAs were diagnosed as atypical (91) or suspicious for malignancy (95). The cytologic smears from all 186 equivocal cases and histopathologic sections from 156 of these patients who underwent a biopsy or mastectomy were reviewed. Clinical follow-up was obtained on the remaining 30 cases. Upon review, the causes of the equivocal diagnoses were divided into three categories: (1) technical, in which the smears were either markedly limited in cellularity or obscured by blood and/or drying artifact; (2) inexperience, which included cases that were reclassified by the reviewing cytopathologist as benign or malignant; and (3) the overlap of cytologic features of benign and malignant lesions due to the nature of the lesion, justifying a confirmational biopsy. Technical difficulties accounted for 103 equivocal diagnoses (4.5%); inexperience of the cytopathologist was responsible for 44 cases (2.4%). The third category, which represents the true gray zone in breast cytology, accounted for 39 cases (2%). Fibroadenomas constituted the largest single cause of equivocal diagnoses (17 cases). These fibroadenomas exhibited very cellular smears with marked discohesiveness and occasional nuclear atypia and prominent nucleoli. Other breast lesions in this category were intracystic papillary carcinoma, low grade apocrine carcinoma, solitary intraductal papilloma, and intraductal and atypical hyperplasia. The remaining lesions, and useful criteria of help with the differential diagnosis of the above categories, are discussed. PMID- 7992577 TI - Secretory carcinoma of the breast. Correlation of aspiration cytology and histology. AB - We analyzed the fine needle aspiration findings in five cases of secretory carcinoma of the breast in adults to clarify their cytomorphologic features and correlate them with their histology. The cytologic smears revealed grapelike clusters of mucous globular structures (MGSs); single MGSs; clusters and sheets of cells with pale green and slightly granular cytoplasm with or without intracytoplasmic vacuolization; some ordinary duct carcinoma-like arrangements; scattered, single, vacuolated cells; some extracellular mucus; and a clean background. The MGSs were globular structures consisting of distinctive vacuolated cells containing large globules of a secretory product. The cytologic findings showed a similar wide variation in the range of histologic appearances; however, the grapelike clusters of MGSs, which corresponded to a microcystic or microfollicular pattern histologically, were present in most cases and should suggest a diagnosis of secretory carcinoma. PMID- 7992578 TI - Fine needle aspiration cytology of accessory axillary breasts and their lesions. AB - Fine needle aspiration cytology (FNAC) of 25 cases of accessory axillary breast tissue was performed during a five-year period. The patients were referred to the cytology clinic with clinical diagnoses of axillary lymphadenopathy (16), accessory breasts (5) and lipomas (4). FNAC revealed accessory breasts in 17 cases, fibroadenoma in 7 and fibrocystic disease in 1. Of the 17 accessory breasts, 12 were clinically thought to be lymphadenopathy or lipomas. FNAC remains an important tool in preventing unnecessary surgery in such cases. PMID- 7992579 TI - Metaplastic carcinoma of the breast in a renal transplant recipient. Initial diagnosis by fine needle aspiration cytology and immunocytochemistry. AB - A 46-year-old woman presented with a mass in the left breast and left axillary lymphadenopathy. Five years earlier she had received a renal transplant from an unrelated donor because of end-stage renal failure secondary to adult polycystic kidney disease. She was on immunosuppression therapy in the form of cyclosporine, azathioprine and prednisolone. Fine needle aspiration cytology of the breast mass showed a metaplastic (sarcomatoid) carcinoma, whereas the axillary lymph node aspirate suggested carcinosarcoma. Immunocytochemical studies revealed dense positivity for vimentin in the sarcomatous component and positivity for epithelial membrane antigen in the epithelial component. Rare cells were positive for cytokeratin. The cytodiagnosis was confirmed by excision biopsy of axillary lymph nodes. The patient died on the fourth postoperative day following left mastectomy and axillary clearance. The histopathology report of the breast tumor showed sarcomatoid carcinoma. PMID- 7992580 TI - Fine needle aspiration cytology of pleomorphic lobular carcinoma of the breast. Duct carcinoma as a diagnostic pitfall. AB - Pleomorphic lobular carcinoma (PLC) of the breast is a subtype of lobular carcinoma of the breast that is well recognized in the surgical pathology literature. Fine needle aspiration (FNA) recognition of this subtype is important, for the subtype characteristically pursues an aggressive clinical course as compared to the classic lobular carcinoma of the breast. The cytologic literature on this entity is nonexistent. We describe the FNA findings in a series of four cases of PLC diagnosed retrospectively, discuss the cytologic features that are useful in the recognition of this entity and the diagnostic pitfalls, and propose classifying these tumors as a high (poor) nuclear grade variant of lobular carcinoma, analogous to the grading scheme in use for aggressive ductal carcinomas. PMID- 7992581 TI - Role of fine needle aspiration cytology after lumpectomy. AB - Lumpectomy with axillary dissection followed by radiotherapy is a frequently utilized technique for the treatment of selected breast carcinomas. Following this procedure, patients often present within a variable period of time with either clinical or mammographic abnormalities at the lumpectomy site suggesting recurrent cancer. In order to evaluate the utility of fine needle aspiration biopsy (FNAB) in the follow-up of such patients, aspirates were obtained 1-73 months after lumpectomy from 72 patients. A spectrum of cytologic changes was seen as a consequence of surgery and irradiation at the site of the lumpectomy as well as in the axilla and lumpectomy scar. The majority of these changes (94%) were benign and generally resolved during follow-up visits. Recurrent malignancy was detected in 4 of 72 patients. These results show that FNAB can reliably differentiate benign from neoplastic changes in postlumpectomy patients and indicate that FNAB may play an important role in the nonsurgical management of clinically alarming but benign postlumpectomy lesions. PMID- 7992582 TI - Immunocytochemical assay of estrogen and progesterone receptors in fine needle aspirates from breast cancer patients. AB - Estrogen receptors (ERs) and progesterone receptors (PRs) were determined by an immunocytochemical assay (ICA) on fine needle aspirates (FNAs) from patients with primary, recurrent and metastatic mammary carcinoma, and the results were compared to those with the biochemical dextran-coated charcoal (DCC) method performed on the surgical sample in order to compare the two methods. The aspirates were suspended in a buffered saline solution, cytocentrifuged onto glass slides and immunocytochemically stained according to the protocol of commercial kits employing monoclonal antibodies specific for ER and PR. Immunocytochemical staining of malignant cells was evaluated on the basis of the percentage of stained cells; 10% staining was taken as the cutoff value. Fine needle aspiration biopsies (FNABs) from 107 breast carcinomas were analyzed immunocytochemically for ER and 31 of them for PR, also. The overall concordance between ICA and DCC was 88% for ER and 87% for PR. The sensitivity, specificity, and positive and negative predictive value of ICA on FNAs as compared to conventional DCC were 87%, 90, 97% and 63%, respectively, for ER and 85%, 100%, 100% and 56% for PR. These findings suggest that estrogen immunocytochemical assays and progesterone immunocytochemical assays on FNAs in breast cancer patients are reliable techniques for evaluating receptor status and can be useful in assessing ER and PR whenever surgical biopsy is not indicated and when information about ER and PR status is required at the time of the clinical diagnosis. PMID- 7992583 TI - Fine needle aspiration cytology of the breast. A review of 1,868 cases using the Cytospin method. AB - The Cytospin method of fine needle aspiration cytology includes flushing the aspirate into 10 mL of Cytospin fluid; the cytocentrifuge preparations are then safely and conveniently prepared in the laboratory. Slides are stained with Papanicolaou stain and hematoxylin and eosin. From November 1989 through October 1992, 1,868 breast aspirates from palpable lumps were examined by this method at our institution. The method detected 398 of 441 cancers (90.2%); of the 43 that were undetected, 16 had inadequate aspirates, and 27 were falsely reported as negative (for a false-negative rate of 6.0%). There were no false positives; the positive predictive value for malignancy was 100%. The inadequacy rate was 14.8%. Excluding inadequate samples, the complete sensitivity was 95.2%, with 96.5% specificity. The Cytospin method of processing breast aspirates from palpable breast lumps is an acceptable alternative to conventional fine needle aspiration using direct smears. It is also highly convenient as an outpatient procedure, obviating the need for skillful preparation of direct smears. PMID- 7992584 TI - Multivariate analysis of prognostic features in malignant pleural effusions from breast cancer patients. AB - To identify prognostic indicators in breast cancer patients with malignant pleural effusions, we analyzed the cytopathologic features of 57 fluids representing the first pathologic diagnosis of a distant metastasis in these women. The specimens were analyzed prior to reviewing the clinical records. The median survival of 55 patients who died of the disease was five months following the effusion diagnosis (range, 1-114). Univariate analysis identified three cytopathologic features that correlated with relatively prolonged survival: arrangement of tumor cells in spheroids, slight nuclear atypia and low mitotic rate. Women whose tumor cells formed spheroids survived a median of 24.5 months as compared to 4 months for women with all other architectural patterns (P = .004). Multivariate analysis revealed that slight nuclear atypia and low mitotic rate strongly correlated with spheroid formation. Since breast cancers that form spheroids in effusions portend a relatively favorable prognosis, we recommend that cytopathologists comment on this pattern when reporting on metastatic breast carcinoma in pleural fluids. PMID- 7992585 TI - Adenomyoepithelioma of the breast. A case report correlating cytologic and histologic features. AB - Adenomyoepithelioma is a relatively recently described benign lesion of the breast. Although the histologic features have been well documented, to the best of our knowledge the cytologic features have not been reported. In this paper we present the fine needle aspiration cytologic features of a case of adenomyoepithelioma and correlate them with histology. The cytologic distinction from other benign and malignant breast lesions and its clinical significance are discussed. PMID- 7992586 TI - Fine needle aspiration cytology of liposarcoma of the breast. A case report. AB - Aspiration cytology has become an accepted procedure in the evaluation of breast abnormalities. Encountering unusual findings in cytologic material, therefore, may become more frequent. We describe a primary liposarcoma of the breast diagnosed by fine needle aspiration cytology and review the cytologic features of liposarcoma in general. The differential diagnosis is considered, and the previous literature regarding liposarcomas of the breast is reviewed. PMID- 7992587 TI - Fine needle aspiration cytology of tubular adenoma of the breast. A report of two cases. AB - During the routine practice of fine needle aspiration of the breast, two tubular adenomas were encountered. The patients were 46 and 69 years of age. In one case the appearances indicated a benign epithelial proliferative lesion, while in the other, epithelial atypia necessitated surgical excision. The differential diagnoses included other benign epithelial proliferative lesions and carcinoma. To avoid inappropriate surgery, the cytomorphologic spectrum of benign epithelial proliferative lesions, including tubular adenoma, must be recognized. PMID- 7992588 TI - Secretory carcinoma of the breast. PMID- 7992589 TI - Nuclear grading of breast carcinoma. PMID- 7992590 TI - A plea for uniform terminology and reporting of breast fine needle aspirates. M.D. Anderson Cancer Center proposal. PMID- 7992591 TI - [Low molecular weight heparins in prophylaxis and treatment of thromboembolic disorders]. PMID- 7992592 TI - [Cyclins and proliferative pathology]. AB - Cyclins are proteins which activate a family of serine-threonine kinases called cdk (cyclin-dependent kinases) responsible for progression through the cell cycle. Human cyclins are divided into two groups: mitotic cyclins (cyclins A and B) which regulate cell division, and G1 cyclins (C, D and E) involved in early stages of cell cycle. Cyclins and their cdk partners participate in the pathogenesis of neoplastic proliferation by phosphorylating some oncogenes and antioncogenes, for example the protein encoded by the retinoblastoma susceptibility gene (pRb). Moreover, hyperexpression of one or more classes of cyclins on the gene, mRNA and/or protein level is sometimes observed in neoplastic cells of different origin, for example the rearrangement of the cyclin D1 gene with ectopic expression of its protein product in centrocytic lymphomas with translocation t(11; 14) (q13; q32). Mitotic cyclins can serve as a marker of proliferating cells. PMID- 7992593 TI - [Platelet transfusion from HPA typed donors in alloimmune thrombocytopenia of newborns and fetuses]. AB - The registry of donors typed for HPA-1 and HPA-3 antigens is presented. Three cases of fetal/neonatal alloimmune thrombocytopenia (F/NAIT) transfused with typed platelets either from mother or from registered donors are discussed. All children were transfused just after delivery, one in addition in utero: they survived not having any haemorrhagic complications in central nervous system inspite of such complications in previous born siblings. In the paper the general rules of platelet transfusions in F/NAIT are discussed. PMID- 7992595 TI - [Treatment of inflammatory changes and stomatitis in patients with acute leukemias and malignant lymphomas using low pressure hydrotherapy--preliminary report]. AB - The management of stomatitis, commonly complicating intensive chemotherapy in patients with acute leukemias and malignant lymphomas has been presented. The hydrotherapy equipment of our own construction was designed to wash the oral cavity with large amounts of fluid given at low pressure and constant temperature. This washing solution contained the addition of drugs; its pH was adjusted to the pH of the patients saliva. Preliminary results of this treatment modality have been reported. PMID- 7992594 TI - [Results of induction treatment with idarubicin for acute nonlymphoblastic leukemia in adults]. AB - Fifty six adult acute nonlymphoblastic leukemia patients were randomised in 1993 year according to Polish Acute Leukemia Group (PALG) into prospective, cooperative trial with the same prognostic factors distribution. The results of induction treatment using idarubicin on days 1, 3, 5 plus arabinoside cytosine 1 7/10 plus etoposide 1-5 (ICE7/10) vs. daunorubicin on days 1-3 plus Ara-C 1-7/10 with additional HD Ara-C in case of not sufficient cytoreduction in 6th day's bone marrow biopsy (3+7/+/-HD) and etoposide in M4-5 subtype are comparable (63 vs. 61% CR). Complete remission was achieved significantly more frequency (p < 0.02) after 1 cycle of induction treatment with ICE7/10 (93%) compared with 3+7+/ HD (55%), and 10 days shorter time to CR was observed. Side effects were comparable in both groups. The program with IDA needed more intensive supportive therapy. PMID- 7992596 TI - The antithrombotic effect of thromboxane receptor antagonist HN 11500 on thrombus formation in laser thrombosis model and platelet function tests. AB - The effect of thromboxane receptor antagonist HN 11500 (Chemie Linz AG, Austria) on thrombus formation in laser thrombosis model and platelet function test has been studied. In this study HN 11500 was a potent antithrombotic agent significantly inhibiting thrombus formation in venules in doses higher than 5 mg/kg after i.v. and 10 mg/kg after oral administration. Lower doses were needed to obtain the same antithrombotic effect when arterioles were investigated. The antithrombotic effect of minimal effective doses of HN 11500 lasted longer than 8 hours in venules and more than 12 hours in arterioles. After oral feeding of this thromboxane receptor antagonist in doses 5 mg/kg, antithrombotic effect in investigated arterioles lasted longer than 16 hours but less than 20 hours. When different doses of HN 11500 were injected i.v. together with r-Hirudin or LMWH CY 216 the inhibitory effect on thrombus formation in venules was stronger and observed with lower doses of HN 11500. In vitro study HN 11500 inhibited platelet adhesion to the siliconized glass, bovine extracellular matrix as well as ADP and collagen mediated platelet aggregation. Lower concentration of this agent were needed to inhibited platelet adhesion to the extracellular matrix than platelet adhesion to the siliconised glass, and ADP and collagen induced aggregation. PMID- 7992597 TI - [Antithrombotic properties of heparin independent of its anticoagulant activity]. AB - Antithrombotic effects of two glycosaminoglycans: LMWH-Fraxiparin (Sanofi) and UFH Heparinum (Polfa) have been studied in the laser-induced rat thrombosis model. The investigations were carried out on male Wistar rats. Thrombus formation was induced in small mesenteric venules 25-30 microns in diameter using argon laser. An interference contrast system based on a Leitz Orthoplan microscope was used for the evaluation of thrombus formation. The number of laser injuries needed to induce a defined thrombus proved to be a useful way to quantitate the results in this thrombosis model. Fraxiparin and UFH showed doses dependent antithrombotic effect in the laser model. Fraxiparin in minimal dose 16 aXa/kg and UFH in minimal dose 15 IU/kg 30 min after i.v. injection to the rats markedly inhibited thrombus formation in small mesenteric venules. Antithrombotic effect of the administration of minimal effective doses of both glycosaminoglycans lasted longer than 4 hours but less than 6 hours. Protamine injected in a dose 1 ml per 5000 U/heparin neutralized anticoagulant activity of both heparins in rat plasma but did not inhibit the antithrombotic effect in laser thrombosis model. After the injection of protamine antithrombotic effect of the investigated glycosaminoglycans was weaker but still observed. Further studies are needed to clarify the factors which are responsible for the antithrombotic effect of heparins after neutralization of their anticoagulant activity (inhibition factors: IIa and Xa). PMID- 7992598 TI - [Platelet defects in chronic myeloproliferative disorders]. AB - Platelet abnormalities are common in patients with chronic myeloproliferative disorders. In this study we report abnormalities in platelets morphology and function in 45 patients with chronic myeloproliferative disorders: 15 with chronic myelogenous leukaemia (CML), 8 with polycythemia rubra vera (PRV), 20 with essential thrombocythemia, and 2 with myelofibrosis (ME). We investigated flow cytometric features of platelets as measured with Technicon H1 technology, VIZ, mean platelet volume (MPV), plateletocrit), platelet distribution width (PDW), and modal platelet volume (PLT Mode) Platelet aggregation in response to ADP, epinephrine and collagen was used as functional test. In patients with ET, PRV and MF we found a significant decrease in platelet volume (both MPV and PLT MODE). Decrease in platelet aggregation and secretion in response to ADP, epinephrine and collagen was the most frequent abnormality in platelets function and was observed in most of patients with thrombocythemia in chronic myeloproliferative disorders. PMID- 7992599 TI - Secretory response of the vessel wall to DDAVP and venous occlusion in von Willebrand's disease. AB - The aim of this study was to compare the secretory response of the vascular wall in vivo to DDAVP (i.v. 0.3 microgram/kg, 30 min) and to venous occlusion (VO, 20 min) in control healthy subjects, patients with von Willebrand's disease type I (vWd I) and patients with von Willebrand's disease type III (vWd III). In controls (n = 10) and vWd I (n = 12), DDAVP induced a 2 to 3-fold rise in plasma von Willebrand factor antigen (vWf: Ag), factor VIII coagulant activity (VIII: C) and tissue--type plasminogen activator antigen (t-PA:Ag). VO was less effective in increasing vWf: Ag and VIII:C but produced a greater rise in t-PA:Ag. Large increments (over 10-fold) were observed in plasmin-alpha 2-antiplasmin complexes following both stimuli. In vWd III (n = 10), DDAVP and VO failed to increase vWf:Ag, VIII:C and t-PA:Ag. No significant changes in plasmin-alpha 2-antiplasmin complexes were observed in this group. Moreover, the baseline t-PA:Ag values were significantly lower in vWd III (2.17 +/- 1.13 ng/ml) than in controls (4.84 +/- 1.97 ng/ml, p < 0.001). A significant increase in urokinase--type plasminogen activator antigen (u-PA:Ag) was found only in controls after VO. Neither controls nor patients with vWd showed any changes in plasma fibronectin levels following DDAVP. The low t-PA:Ag results and the abnormal fibrinolytic response to DDAVP and VO in patients with severe (type III) vWd indicate that their endothelial cell abnormality is more extensive than the defect in the synthesis or release of vWf. PMID- 7992600 TI - [In vitro study about the influence of recombinant interleukin-8 on human hematopoiesis]. AB - The influence of the recombinant human Interleukin-8 (IL-8) on in vitro clonogenicity of human bone marrow progenitors from the different haemopoietic lineages has been evaluated. Two different forms of IL-8 were used in this study: the longer one of the endothelial and shorter one of the monocytic origin. The bone marrow cells before the plating were enriched in CD34+ cells. We did not confirm that endothelial derived IL-8 inhibits the CFU-GM, BFU-E and CFU-Meg colony formation. Similarly monocytic IL-8 did nor inhibit neither the CFU-GM not the BFU-E colony growth. Nevertheless, small inhibitory effect of monocytic derived IL-8 have been found on the CFU-Meg colony formation. PMID- 7992601 TI - Rearrangement of T-cell receptor delta/gamma genes: application to the study of clonality in childhood B-lineage acute lymphoblastic leukaemia. AB - DNA-based PCR with various sets of primers for T-cell receptor gamma/delta (TCR gamma/delta) chain genes was used to study clonality in childhood B-lineage acute lymphoblastic leukaemia. TCR delta genes rearrangements were the most common and were observed in 77 patients (64.2%). The typical pattern of rearrangements was defined as an incomplete V delta 2 to D delta 3 or to D delta 2 recombination product. Rearrangements of TCR gamma genes were observed in 61 cases (50.8%). Predominantly, TCR gamma genes rearrangements were detected in null-ALL and the early B-ALL (55.2% and 60%, respectively) and were rather rare in other groups. From all eight V segments of V gamma l group rearrangements concerned mostly regions V gamma 2, V gamma 4 and V gamma 7. We have confirmed that TCR gamma and delta genes amplification provides a rapid, sensitive method for assessing clonality in ALL almost in 100%. PMID- 7992602 TI - [Larsen syndrome: multicenter study of 12 new cases. Diagnosis, planning and results of treatment]. AB - Larsen's syndrome is characterized by the association of congenital knee, hip and elbow dislocations, characteristic facial abnormalities, joint hyperlaxity, and other inconstant malformations. A review is made after description of 12 new cases from a multicenter study. A partial modification of diagnostic criteria is proposed, based on the analysis of the frequency and localization of the deformities. Radiological aspects, surgical indications, clinical evolution, complications and late results are presented, with emphasis on lower extremity problems. Good clinical results are more remarkable in the children treated early. Periodic follow-up is obligatory for good therapeutic results. PMID- 7992603 TI - Hemiarthroplasty in elderly, debilitated patients with an unstable femoral fracture in the trochanteric region. AB - The purpose of this study was to evaluate the results of patients with an unstable fracture in the trochanteric region who were treated by hemiarthroplasty. During a 10-year period, 154 of the 308 patients with a trochanteric fracture treated in our hospital had an unstable fracture. In patients with severe comminution and osteoporosis an endoprosthesis was inserted: 5 patients with a subtrochanteric and 17 with a pertrochanteric fracture. Ten patients suffered from central nervous system diseases, and in 10 patients cardiovascular or pulmonary disorders were diagnosed. Pre- and postoperative ambulation levels were classified. Seventeen patients (77%) achieved full weight bearing mobilization. Five patients never walked again (23%): 2 patients died in the first month (9%). It is concluded that for elderly and debilitated patients with an unstable trochanteric fracture, hemiarthroplasty is an acceptable alternative to osteosynthesis. PMID- 7992604 TI - [Reconstruction of the acetabulum using femoral head autograft in total hip arthroplasties]. AB - We have reviewed, at a mean follow-up of 63.7 months, 36 total hip replacements performed with bulk acetabular autograft. Before surgery all the hips had acetabular insufficiency. Improvement of acetabular coverage was achieved in all cases with the patient's femoral head screwed to the ilium. Only one massive graft resorption was observed, simultaneous to loosening of the socket. Partial graft resorption was observed in 6 cases, and was not correlated with loosening of the socket. In all cases we observed radiographic features consistent with graft incorporation. Periprosthetic ossifications were noted in 13 cases. At follow-up, four sockets were loose, among which were included three Weill threaded rings. The mean functional improvement scores evaluated with the Merle d'Aubigne hip rating were: 4 points for pain, 2.7 points for mobility, and 2.4 points for walking. The authors concluded that femoral head, used as a massive autograft during total hip replacement, was a safe procedure for bone stock reconstruction in case of severe acetabular insufficiency. PMID- 7992605 TI - The clinical significance of suction drainage cultures. AB - A prospective study of 72 operations in which one or more suction drains were inserted, showed that cultures of the drains did not have any predictive value for the development of signs of infection. Protracted suction drainage could, however, increase the risk of postoperative infection. PMID- 7992606 TI - Bacterial contamination of allografts. AB - The risk of bacterial infection through allogeneic bone transplantation is one of the problems facing tissue banks. The purpose of this study is to report the contamination rate in 987 grafts obtained under strictly aseptic conditions, between 1989 and 1992. The grafts were stored at -80 degrees C (cortical bone and tendons) and -40 degrees C (cancellous bone). The overall contamination rate was 6.6%, with Gram-positive bacteria responsible for 80% of the positive cultures. We discuss the sources of contamination, the most frequently isolated bacteria and the steps in the donation and transplantation procedures that help to reduce the risk of contamination. We conclude that the methods of procurement, processing and storage of tissues are effective in making sterile allografts available. PMID- 7992607 TI - [Characteristics of fractures of the distal part of the clavicle in children]. AB - Fractures of the clavicle are frequent in children and mostly affect the middle third. On the other hand, traumatic fractures of both medial and lateral thirds of the clavicle are rare. The lesions have special characteristics: difficulty in diagnosis for the medial third; risk of callus formation in the absence of surgical reduction of the lateral third. The authors report two observations of fractures of the medial and lateral thirds of the clavicle; they insist on the value of investigation by CT scan. PMID- 7992609 TI - Operative treatment of clavicular nonunion. AB - Twelve patients treated for clavicular nonunion mainly with plate fixation and bone grafting were reviewed in order to evaluate the treatment. Follow-up was a median of 41 months (20-117). Nine out of 12 patients achieved a good end result, but the primary treatment failed in half of the cases, probably because of short (4-hole) semitubular plates and insufficient postoperative immobilization. We conclude that 4-hole semitubular plates cannot be recommended for treating clavicular nonunion because of a high risk of failure. Sufficient postoperative immobilization should follow plate fixation. If this is respected, plate fixation with bone grafting appears as a good method for treating clavicular nonunion. PMID- 7992608 TI - Surgical treatment of Allman type III acromio-clavicular dislocation. A long-term follow-up study. AB - The authors report the results of a long-term follow-up study of surgical treatment of Allman type III acromio-clavicular dislocation. Despite numerous publications regarding the validity of closed treatment, the authors believe, in accordance with the anatomo functional and pathological knowledge, that open treatment is justified not only in young people but in older ones too. Among the different techniques, the authors prefer acromio-clavicular fixation with threaded wires because the operation time is short and the functional results are good with the lowest number of complications. PMID- 7992610 TI - [Heyman's operation for the treatment of congenital metatarsus varus]. AB - The authors report their experience with the operation of Heyman, i.e. complete release of the tarsometatarsal and intermetatarsal joint for the treatment of congenital metatarsus varus. This operation of Heyman is capable of meeting the requirements of correction if the indications are precise and if the surgical technique is perfect. The operation is indicated in cases of varus over 15 degrees, passively reducible, with good axes of the hindfoot and without bony alterations of the Lisfranc joint, in children between 3 and 8 years old. There should be a dorsal and medial capsulotomy, with section of the medial 2/3 of the plantar aspects of tarsometatarsal and intermetatarsal capsules; the lateral portion, the lateral 1/3 of the capsule and the insertions of the fibularis brevis and tibialis anticus should be spared. A complete capsulotomy is not indicated owing to the risk of dislocation of the tarsometatarsal joint. The correction should be stabilized during the operation by Kirschner wires to avoid a loss of correction when putting the foot in plaster. PMID- 7992611 TI - Validity and diagnostic bias in the clinical screening for congenital dysplasia of the hip. AB - To assess the validity of the clinical maneuvers and signs in the screening for congenital dysplasia of the hip and the presence of a diagnostic bias in this screening, a random sample of 261 newborns was studied at a tertiary hospital. All newborns were clinically and sonographically studied in the first 48 hours after birth. Hips were classified according to Graf's scheme. Sensitivity, specificity and predictive values were estimated. Nineteen dysplasias and 100 physiologically immature hips were detected. Sensitivity and specificity for the Ortolani-Barlow maneuver were 26% and 84% respectively. A higher sensitivity was observed when all clinical maneuvers/signs were considered; however, specificity decreased, so the positive predictive value reached a similar figure to that of Ortolani-Barlow, 5%. A higher positive rate with the Ortolani-Barlow procedure was observed when newborns had risk factors for congenital disease of the hip (family history and female sex) or belonged to groups that could be considered as high-risk (low Apgar score, younger mothers). Other procedures apart from clinical examination should also be recommended as an effective screening procedure to decrease the number of cases missed and to avoid diagnostic bias in future epidemiologic research on this condition. PMID- 7992612 TI - Unstable femoral neck fractures treated with a 130 degrees blade plate. AB - We reviewed 32 patients who sustained an unstable intracapsular hip fracture, treated with an AO 130 degrees blade plate. The low incidence in complications (avascular necrosis 7%, delayed union 3%, no nonunion or loss of fracture reduction) compares favorably with previous reports. Experience with this highly demanding surgical technique is however essential to obtain good results. PMID- 7992613 TI - Larsen's syndrome with mixed-type hearing loss. AB - Mixed-type hearing loss is an extremely rare feature of Larsen's syndrome, a complex of symptoms characterized by multiple joint dislocation and "flat" faces. In this report, a patient with bilateral mixed-type hearing loss and Larsen's syndrome is presented. PMID- 7992614 TI - Delayed diagnosis of high-pressure injection injuries to the finger. A case report and review of the literature. AB - High-pressure injuries to the finger are often under-estimated. Nevertheless, early diagnosis and debridement are absolute requirements to save the finger and to restore function. Delayed diagnosis may lead to severe infection and often ends in amputation. PMID- 7992615 TI - Giant lipoma of the deep palmar space, mimicking persistent carpal tunnel syndrome. AB - In a patient with persisting signs of median nerve compression, a giant lipoma of the deep palmar space was discovered during revision surgery. All symptoms disappeared postoperatively. PMID- 7992616 TI - Tibial tuberosity avulsion associated with patellar tendon avulsion. AB - We report an adolescent boy with avulsion of the tibial tuberosity associated with avulsion of the patellar tendon. He underwent open reduction and internal fixation of his bone injury, and the patellar tendon was successfully reattached. The boy experienced a full recovery. PMID- 7992617 TI - Compartment syndrome after fracture of the distal radius. AB - A compartment syndrome of the forearm after a fracture of the distal radius is presented. This rare complication should be considered after high velocity trauma in young people. In this setting, we prefer general anesthesia for fracture reduction. Fracture fixation and avoidance of circular casts are recommended. Repeated evaluation allows early detection of compartment syndrome. Fasciotomy should be done if this syndrome occurs. PMID- 7992618 TI - Slipped capital femoral epiphysis in primary juvenile hypothyroidism. AB - We report a case of a patient with a unilateral slipped upper femoral epiphysis and primary juvenile hypothyroidism. A satisfactory outcome was observed two years after surgery. PMID- 7992619 TI - [Effects of arterial blood pressure change on release of GABA in the posterior hypothalamus conscious of freely moving rats]. AB - Push-pull superfusion technique was used to investigate the release of endogenous gamma-aminobutyric acid (GABA) in the posterior hypothalamus of the conscious, freely moving rat in response to peripherally applied drugs or experimentally induced blood pressure changes. The rise in blood pressure elicited by intravenous infusion of phenylephrine (15 micrograms.kg-1.min-1) or blood (3 ml/100 g) was associated with an increased rate of GABA release in the posterior hypothalamus. Hypotension produced by nitroprusside (30 micrograms.kg-1.min-1), chlorisondamine (3 mg.kg-1,iv) and controlled bleeding (3 ml/100 g) led to a counteracting decrease in hypothalamic GABA outflow. This finding suggests that GABAergic neurons of the conscious, freely moving rat in the posterior hypothalamus are involved in cardiovascular control and possess a hypotensive function. PMID- 7992620 TI - [Studies on the antitumor activity of organotin compounds]. AB - Organotin compounds were found to obviously inhibit the activity of phospholipid/Ca(2+)-dependent protein kinase (PKC) in rat brain tissue and the proliferation of tumor cell lines in vitro. The results showed that a correlation exists between the effects on PKC and anti-proliferative and antitumor activities. The structure-activity relationship was shown to be as follows: (1) R, the organic group determines the biological activity; (2) electronegativity of the halogen can affect the activity. The organotin compounds inhibit tumor cells by its [SnR2]2+, and inhibit G1-->S phases of HL-60 cell cycle. The IC50 of [SnPh2F2], [SnPh2(CysOS)].H2O and [SnPh2Cl2.phen(CH3)2] are respectively 25, 15 and 20 mumol.L-1 on PKC, 0.5, 4.0 and 0.3 mumol.L-1 on HL-60 cells, 2.7, 9 and 1.5 mumol.L-1 on BEL-7402 cells, 2.2, 15 and 5.0 mumol.L-1 on KB cells. But no induction of differentiation of leukemic cell lines HL-60 and K562 was observed. PMID- 7992621 TI - [Effect of acetylsalvianolic acid A on platelet function]. AB - Acetylsalvianolic acid A (ASAA) is an semisynthetic analogue of salvianolic acid A, isolated from Danshen (Salvia miltiorrhiza Bunge). In in vitro experiments, ASAA showed marked inhibitory effect on rat and rabbit platelet aggregation induced by ADP, collagen, arachidonic acid (AA) and thrombin. In ex vivo experiments with ADP, collagen, and AA as inducers, ASAA was also shown to inhibit platelet aggregation remarkably. The effect lasted more than two hours. In addition, ASAA was found to have suppressive effect on collagen induced platelet 5-HT release while inhibiting aggregation. The above results seemed to suggest that ASAA may be a widely effective inhibitor of platelet function. PMID- 7992622 TI - Synthesis and biological activity of atriopeptin III and its small molecular analog. AB - Atriopeptin III (AP III) and its small molecular analog were synthesized manually by stepwise solid-phase method. The peptides were oxidized with iodine in 30% acetic acid at very high dilution to form intramolecular disulfide bridge and purified to homogeneity by conventional means, including Sephadex G15, dialysis and reversed-phase HPLC. Bioassay study demonstrated that the synthetic AP III possesses potent bioactivities identical to those of the same product of Peninsula Lab both in vitro and in vivo; whereas the linear peptide, having the same primary structure as AP III, showed very limited bioactivity. The small analog, with Ser-Ser-residue deleted from the N-terminal of AP III, was equipotent as AP III while exhibiting a longer half-life in vivo resulting from the peptide modification. PMID- 7992623 TI - [Studies on antiviral agents: synthesis of tai-ding-an analogs]. AB - Tai-Ding-An (3-phthalimido-2-oxo-n-butyraldehyde bisthiosemicarbazone, TDA) is a synthetic antiviral drug developed by our institute. Because of its low water/lipid solubility. Tai-Ding-An is limited to topical treatment of herpes viruses infected skin diseases and of condylomata acuminata (ginital warts), one of sexual transmitted diseases (STD), caused by human papilloma virus (HPV). Ten TDA derivatives IIIb-e, Va, Vb, VIIa-e have been synthesized in order to search for compounds with higher antiviral activity and better solubility than the parent compound as well as to explore structure and activity relationship. Among the ten analogs, three compounds (IIIc, VIIa and VIIb) were found to be effective against herpes simplex virus. The most potent inhibitor was 3-phthalimido-2-oxo-n butyraldehyde bis- N4- phenylthiosemicarbazone (IIIc, PTDA) which was approximately 10 times more active against HSV-2 as compared with TDA. Compound IIIc was also found to be effective on the topical treatment of herpetic epithelial keratitis in rabbits. PMID- 7992624 TI - [Synthesis of tyrosine-related peptide and their effect on progesterone production]. AB - Twenty peptides containing hydroxy-amino acids have been synthesized manually by stepwise solid-phase procedure. The chloromethyl resin and MBHA resin were used as solid supports. A new reagent of 0.5 mol.L-1 DDSi/1.5 mol.L-1 phenol/DCM was applied for the removal of N alpha-Boc group. TFMSA was the cleaving reagent. After purification by C-18 column; all products were assayed according to amino acid analysis. The bioactivity of synthetic peptides was tested for the effect on progesterone production in vitro. Eight peptides, GlyTyrAlaLys, (SarSer)2Lys and its methyl ester, TyrLys, HisTyr-NH2, ThrProTyrLys-NH2 TyrThrProArgLys and AspHisProThrPheLys showed significant effect on inhibiting hCG-induced progesterone production, and first three of them could also inhibit basal progesterone secretion. However, peptide GlySerTyr exhibited stimulative activity on basal progesterone secretion. So far, no reasonable relationship between structure and bioactivity was found. PMID- 7992625 TI - [Determination of salbutamol in human urine]. AB - Salbutamol (2.4 mg) was administrated to a healthy male. The urine was analysed by GC-MS. 95% of the drug was excreted in 24 h in unconjugated form. The pH of urine was shown to strongly affect the extraction rate, good recovery was obtained at pH 8.8. With this method, salbutamol can be determined simply, quickly and accurately. PMID- 7992626 TI - [Effect of panaxadiol saponin (PDS) on phorbol ester induced change of protein kinase C activity in cardiomyocytes]. AB - Partially purified protein kinase C and protein kinase A were separately incubated with various concentrations of PDS (1-1000 micrograms.ml-1) for 10 min in vitro. The results indicate that protein kinase C activity was inhibited in a dose-dependent manner by PDS, but type I and type II protein kinase A were not. In cardiomyocytes preincubated with PDS (250, 500, 1000 micrograms.ml-1) for 10 min, PMA-induced decrease of cytosol protein kinase C activity and increase of membrane protein kinase C activity were greatly inhibited in the same manner. These results suggest that PDS not only inhibited protein kinase C in vitro, but also inhibited activation of protein kinase C in cardiomyocytes. PMID- 7992627 TI - [Studies on compounds of cancer chemoprevention: synthesis of some amides]. AB - In search for cancer chemoprevention agents, seven new amide compounds have been synthesized. The structures have been determined based on spectral and chemical data. N-4-(ethoxycarbophenyl)-alpha-naphthamide and N-4-(ethoxycarbophenyl)-beta naphthamide were shown to be 81% and 79% effective, respectively, for inducing different in HL-60 human promyelocytic leukemia cells at the concentration of 10( 5) mol/L in NBT tests. PMID- 7992628 TI - [Prophecy, utopia, prognosis: forms of the future]. PMID- 7992629 TI - [Drugs epidemiology]. AB - Any drug can be construed as a universal marker of physicians' tasks and knowledge (or ignorance thereof). Presently, pre-marketing studies and trials imply that, after a thorough, basic and/or preclinical research has been conducted, a clinical research stage is in a position to be carried on over a 4- to 6-year lapse of time so that all necessary data are collected thus paving the way for the marketing of the drug involved to be eventually authorized. In most countries, an adequate regulation framework is required in order to eliminate unnecessary drugs, besides setting up efficiency, innocuousness, and purpose criteria for new drugs to be approved. PMID- 7992630 TI - [Maternity, sterility and reproduction technology]. AB - The idea of maternity--and paternity as well--reaches far beyond the field of biological reproduction inasmuch as it implies a subject's desire, besides being regulated by the symbolic order: Language, myths, patterns and values of a given culture. From this point of view, infertility cannot be considered as a mere somatic illness, but as a human problem implying psychological and social aspects that require a search for solutions unlikely to be reduced to a sole medical operation. The development of the new reproductive technology is in keeping with the increasing medicalization of human lives, human sexuality, and human bodies. PMID- 7992631 TI - [Rational use of psychotropic drugs and social communication role]. AB - Extra-clinical factors about the influences affecting the prescription and use of drugs are reviewed. Special attention is given to regulatory agencies, the pharmaceutical industry, and mass media. The problems and public health consequences of the irrational use of drugs are rarely documented in Latin America. Analysis of these factors, information sources, and rational use of psychotropic drugs will require multiple strategies such as social communication and policy formulation to define goals and objectives related to population information, doctors' and individual citizens' decision making processes, and participation of consumers in improving the use of psychotropic drugs. PMID- 7992632 TI - [Evaluation and intervention in demented patients: capacity approach or deficiency approach?]. PMID- 7992633 TI - [Psychiatric and social aspects of AIDS. Report of 4 cases]. AB - A report of four AIDS-related psychiatric cases in Honduras is presented. (2,544 AIDS cases have been reported up to April '93. In the sole city of San Pedro Sula, 1,000 cases have been reported). Measures are suggested for an improved psychiatrical and psychological care of patients (either seropositive patients or AIDS healthy carriers): the former would be helped toward a smoother acceptance of an impending death, the latter could be in a better position to fight against social prejudice and discrimination. PMID- 7992634 TI - [Internal coherence of reasoning in a psychiatric patients group]. AB - This experimental work was aimed at evaluating the internal coherence of reasoning. Several inferential structures of premises have been also typified so that the relationship likely to be established among these variables, and the specific characteristics of the samples involved could be assessed. Population included 50 psychiatric patients, and 50 sound control subjects. Both samples were administered Lopez-Alonso's Test of Reasoning Coherence. From such evaluations, total scores of logical incoherence mistakes as well as inferential structures of premises have been extracted. Results suggest that the psychiatric patients sample lacks a good control on the cognitive reversibility, hence adhering to more atypical structures based on reductionist criteria that give rise to a large number of mistakes coupled to a much more incoherent, and disorganized reasoning pattern. PMID- 7992635 TI - [Daily stress, depressive mood and suicidal ideation in Mexican adolescents]. AB - Among adolescents--especially, early adolescents, social relationships with your peer group are an important element so that new, mature social relationships can be established, with your best friends (peers) competing with your family. Obviously, this new relationship system demands both negotiations and arrangements, while bearing on your emotional state. Hence, the importance of the daily psychosocial stress, since stress is related to the relationship between an individual and his or her environment--an environment likely to outmatch personal psychosocial resources. The present work is aimed at identifying a relationship between some social daily stressors, depressive disturbance, and suicidal ideation among Mexican adolescents. Findings suggest that among male and female adolescents, conflicts with the best friend correlate strongly with a depressive mood also tending to somatizing discomfort: Besides enduring negative affect and somatization, females also tend to feel awkward in their interpersonal relationships, and also suffer from suicidal ideation. So, it could be assessed that a depressive disturbance assumes a different psychopathoplastic expression according to subjects' gender. PMID- 7992636 TI - [Darwin and the scientific study of behavior]. AB - Interest in the study of behavior is ubiquitous in the works of Darwin's. Its influence upon the development--either direct or indirect--of the psychological science extends itself from methods to conceptions about human beings, and social ethics as well. Both the structure and scope of behavioral research have been influenced by Darwin's repositioning of humankind within Nature. PMID- 7992637 TI - [Comorbidity]. PMID- 7992638 TI - [The movement of articles received by Acta Medica Portuguesa]. PMID- 7992639 TI - [Clinical medicine and informatics]. PMID- 7992640 TI - [Reflections on the course of neonatology]. PMID- 7992641 TI - [The clinical implications of the characteristics of uteroplacental flow in pregnancy complicated by hypertension]. AB - The study of the relationship between maternal and perinatal outcome with uterine blood flows using a continuous wave Doppler unit, in hypertensive patients was the aim of our work. One hundred and thirty seven pregnant hypertensive women seen and delivered at the Department of Obstetrics, Santa Maria Hospital, Lisbon, were included in the study. Blood flows were classified as abnormal if and when the systolic/diastolic ratio was > 2.8 and/or a diastolic notch was seen in one or both uterine arteries. The cases were divided in 2 groups (normal/abnormal) according to the uterine blood flow and correlated with maternal and perinatal outcomes. Twenty-three of 26 maternal complications occurred in cases with abnormal uterine artery blood flow; we also found the large majority of perinatal complications within this group (100% perinatal deaths, 88% of the intrauterine growth retardation, 92% preterm deliveries, 93% fetuses with absent or reverted diastolic umbilical flow, 88% cardiotocographic patterns of fetal distress and 84% of the newborns admitted to the neonatal care unit). In conclusion, in pregnancies complicated by hypertension, uterine artery blood flow evaluation by continuous wave Doppler may identify a set of patients needing closer prenatal surveillance. PMID- 7992642 TI - [The sex distribution of congenital cardiopathies]. AB - For 17 years, 4150 infants and children under 13 years of age with final diagnosis of well defined congenital heart disease were studied and the pattern of sex differences are reported. In general, the sex distribution was equal: 2108 males (50.8%) and 2042 females (49.2%) with a male to female ratio of 1.03. Male sex predominance was marked for the following specific lesions: aortic stenosis (valvar and subvalvular) (70%), coarctation of the aorta (66%), transposition of the great arteries (60%), univentricular heart (76%), tricuspid atresia (63%), Ebstein anomaly (76%), hypoplastic left heart syndrome (85%), vascular rings (77%) and right midventricular stenosis (70%). Female sex predominance was marked for the following specific lesions: Persistent ductus arteriosus (72%), atrioventricular septal defects (62%) supravalvular aortic stenosis (71%) and isolated infundibular pulmonic stenosis (80%). A more balanced sex distribution was confirmed for cases of congenital rubella syndrome with persistent ductus arteriosus as isolated cardiovascular malformation (56%). The Importance to establish the sex dominance is emphasized as predictive of recurrence risk of congenital heart disease. PMID- 7992643 TI - [Neural tube defects. The 10-year experience of a central maternity hospital]. AB - OBJECTIVES: 1) To determine trends in prevalence of neural tube defects and the impact of therapeutic abortion. 2) To review perinatal management of spina bifida. DESIGN: All spontaneous and therapeutic abortions, still births and live births affected by neural tube defects registered in Alfredo da Costa Maternity in Lisbon, from 1983 to 1992, were retrospectively analysed. RESULTS: Eighty-two cases with neural tube defects are reported and myelomeningocele and anencephaly++ were the most frequent ones. Total prevalence for all defects was 0.78:1000 births with a small upward trend during the last two years. Birth prevalence was 0.6:1000, with a clear downward trend, due to therapeutic abortion. Prenatal diagnosis improved significantly, from 9% of all defects detected in 1983-87 to 77.5% in 1988-92. Since 1989, all cases of anencephaly were detected before birth. Most cases of spina bifida were vaginally delivered, and elective cesarean section occurred in 4. Early closure of the defect was undertaken in 87.6% of the newborns with open spina bifida. CONCLUSION: While total prevalence of neural tube defects remained stable, with only a small upward trend, prenatal diagnosis and therapeutic abortion resulted in a 56.3% fall in birth prevalence. Optimal management of open spina bifida demands a multidisciplinary team with an individual program for each case. PMID- 7992644 TI - [Carotid-cavernous fistulae. The diagnostic and therapeutic prospects]. AB - Even though in clinical practice carotid cavernous fistulas (CCF) are not a frequent pathology, it should be a diagnostic hypothesis in face of a suggestive clinical presentation. We intended to review the diagnosis and the therapeutics, comparing them with the actual perspectives. Files of 25 patients with the diagnostic hypothesis of CCF, confirmed by conventional angiography in the HSAC Neuroradiology Department, were reviewed. In this group of patients, (5 males and 20 females), the fistulous aetiology was spontaneous in 10 and traumatic in 15. Clinically the symptom most often presented was diplopia (23 cases) and the most frequent encountered sign was ophthalmoplegia (20 cases). Of the Neuroradiologic investigation, CT scan (done to all patients) have shown an prominent superior ophthalmic vein as the most frequent abnormality. Angiographic study was based on Lasjaunias et al protocol (Surgical Neuroangiography, Vol. 2, Springer-Verlag). Surgery was the therapeutic approach for the traumatic fistulas; only 2 of the spontaneous were treated by endovascular route. Three patients are still under observation. In all the others cases there was a fistula exclusion. PMID- 7992645 TI - [A case of Cotard's delusion of negation]. AB - The authors present a clinical case of a 66-year-old man with melancholy of involution with delusion negation, ruin and damages of. The clinical case was interpreted as Cotard's delusion. To the purpose of this case, the authors make a brief examination of the psychopathological, clinical and nosological aspects of this syndrome. PMID- 7992646 TI - [Acute polyradiculoneuritis associated with boutonneuse fever]. AB - We have recorded three cases of Mediterranean fever harboring peripheral nerve involvement. According to the time of occurrence of the neurological symptoms, the cerebrospinal fluid analysis and electromyographic features, we admit that the peripheral nervous system can be involved in two ways in this disease. One due to the direct action of the pathogenic agent, giving place to a vasculitis. The other by an immunological mechanism originating a Guillain-Barre syndrome. PMID- 7992647 TI - [The projects and activities of the Ethics Committee of the Hospital Garcia de Orta]. PMID- 7992648 TI - [The computerized clinical record: merely an academic discussion or an essential technology?]. AB - The publication of the results of a study on improving patient records, recently completed by the Institute of Medicine of the National Academy of Sciences, in the United States, where it was concluded that the Computer-Based Patient Record (CPR) was an essential technology for health care, witnesses the importance and expectations that patients, physicians and other health care professionals, hospital administrators and health systems managers, place on forms of management of clinical information that are more accurate, complete and efficient than what is possible with current methods. A large amount of work is in order, to develop standards for sharing clinical data between clinical information systems and for representing medical terminology and knowledge, to create legislation regarding data protection in CPR, and for the preparation of health care professionals for the information and technological demands of the future. Recent developments in database integration, and the experience of several CPR systems developed at academic institutions, have led to the progressive delineation of the architecture of modern CPR systems. PMID- 7992649 TI - [The computerized clinical record. Myth and reality]. AB - The state of the art in medical informatics is presented, in science as well as in the technological field. After the inventory of the solutions provided it is postulated that informatics and medicine are inevitable partners, but it is a globally positive marriage. PMID- 7992650 TI - [The radiological pattern of cochlear otosclerosis. A CT study of 14 patients]. AB - In this review of cochlear otosclerosis 14 cases were studied by CT scan aiming to establish a densitometric pattern of the capsular foci and relating it to the hearing and vestibule dysfunctions. Severe demineralization with characteristics of probable activity (increased lucency of 30-40%) was demonstrated in the capsular foci. These were mainly cochlear with endosteal involvement (93%): large (64%) or discrete (29%). Cochlear otosclerosis was widespread in 64% of the patients, with coexisting foci in the semicircular canals (38%), vestibule aqueduct (43%) and internal auditory canal (43%). The antefenestral component with stapes involvement was 85%, mostly of the anterior polar and crural varieties (64%) and signs of activity. In 2 patients there was a conductive hearing loss in the tonal audiometry, pure or combined; in 2 others there was only a pure perceptive hypoacusis of type IV. A direct relationship was noted (64% of cases) between the most serious hypoacusis (type III and IV) and the endosteal extension of the cochlear foci. Vertigo occurred in 36% of the patients and was attributed to the posterior labyrinth foci. PMID- 7992651 TI - [The microbiological profile of nosocomial infection in a respiratory intensive care unit]. AB - In 1987, in the Respiratory Intensive Care Unit of Santa Maria Hospital we developed a nosocomial surveillance program with specially created software that provides knowledge of NI in the ICU at any moment. The information gathered along the time is particularly useful in the correlation of the risk factors, the most frequent microorganisms and in the institution of empiric antibiotic therapy. Out of 2528 patients admitted in our ICU for the last 6 years (87/92), 10% had bacteriologically identified NI. Almost (93%) of them had occurred in mechanically ventilated patients, which corresponds to 20.7% NI in those patients. The gram-negative appeared in 63.37%, with the predominance of Enterobacteriaceae. From the gram-positives the most frequent were Staphylococcus spp. Their meticiline resistance was worrisome. NI patients had significantly higher severity and therapeutic intervention scores. Mechanical ventilation period was 4 fold higher and mortality 2.5 times higher in the patients with this complication. PMID- 7992652 TI - [Ritual circumcision and the plastic repair of phimosis]. AB - The AA. describe two variations of their personal technique of foreskin plasty for phimosis treatment. They utilize a variation of Duhamel procedure, with incision of foreskin dorsal face in italic S in cases where the striction ring is moderate and allows a slipping with glandular exposure. They resected ad minima the foreskin in the cases of very serious phimosis and make a YV plasty on the dorsal face, and if necessary a small excision a la demande of the remaining ventral skin. They achieve a good aesthetic result in both techniques and most of operated cases are hard to distinguish from a normal foreskin. The plasties with foreskin maintenance tend to be used in the modern European culture, where the rites disappeared and hygienic habits gained roots. With the exception of religious reasons or strict medical indications (diabetes, skin lesions, etc.) the phimosis repair by mutilation procedures tends to disappear. PMID- 7992653 TI - [A posttraumatic visual defect with late exacerbation associated with an aneurysm of the cervical internal carotid artery]. AB - A posttraumatic visual deficit which worsened eleven weeks later, with sudden visual loss, is reported. The neuro-ophthalmologic examination was suggestive of central retina artery occlusion. The intra-arterial angiography revealed a traumatic pseudo-aneurysm of the ipsilateral high extracranial portion of the internal carotid artery. Based upon the clinical examination, the hypothesis of embolization has been considered the most probable mechanism, which is a rarely described etiopathogenesis. The clinical, pathogenic and diagnostic aspects of this situation are discussed. Finally, the authors describe the treatment, which consisted of the occlusion of the internal carotid artery with detachable latex balloons. PMID- 7992654 TI - [An estimate of the prevalence of dementia and Alzheimer's disease in Portugal]. AB - The authors projected to the Portuguese population the data on prevalence of dementia and Alzheimer's disease obtained respectively by Hofman et al. and Rocca et al through reanalyses of European epidemiological studies conducted or published between 1980 and 1990. The projection relies on the fact that the results of these reanalyses are extensive to all European countries. With this projection which is based on the Portuguese population census of 1991 the numbers of about 92.470 demented patients and about 48.706 Alzheimer's patients are obtained for Portugal. The authors think that, until systematic epidemiological studies of dementia and Alzheimer's disease are available in Portugal, the data now provided are useful for the planning of the care of these patients. PMID- 7992655 TI - [Bases for the teaching of oncology]. AB - We define the parameters for preclinical and postgraduate teaching in oncology coupled with hematology with a view to train competent physicians in these areas as well as to encourage a restructuring of the health system to permit optimal delivery of care to all people. We analyze and define curricular changes in the medical schools to be implemented at a national level with the introduction of an intensive course in hematology-oncology during the clinical clerkships. This course would require a host of appropriate teachers, continued monitoring and a final appropriate written exam. The Oncologic training of the medical student requires an interdisciplinary approach with an emphasis on the personalized approach to the patient with cancer. The postgraduate training should follow minimal guidelines established by the ESMO, EORTC and ABIM with an emphasis on combined training in oncology/hematology, following appropriate training in internal medicine. A need for continued "recycling" of generalists in oncology is felt to be important. Other issues discussed include: methods of teaching and their evaluation; the career pathway for the scientist (docent) in oncology; preventive medicine and finally the need for continuing medical education. An evaluation of the quality of medicine and of ethical and professional conduct while not specifically linked to oncology is considered a vital part of medical care and needs to be placed in perspective. PMID- 7992656 TI - [The physician facing the evolution of ethical concepts in our times]. AB - Medical ethics institutionalized with clinical activities being determined by the patient's interests as they developed in the doctor-patient relationship. The ethical nature of the health concept was emphasized in the positive definitions of health such as the one by the W.H.O.. The established goals for clinical intervention surpass the effective medical capabilities. The curricula of medical schools will have to be reviewed in light of these goals. We characterized the contemporary values and the way medicine has adapted to them: superspecialization and doctors' change in social image brought about by the impact of technocracy in clinical activities, increasing costs of medical care, the interference of non medical managers in the process of clinical decision, litigation and breaches of confidentiality. Technical and social developments lead to new ethical problems in which the moral principles of the doctor can be confronted with patients' demands in situations of difficult choice. Contraception, abortion, genetic engineering, transplants, allocation of scarce resources, the expansion of drug dependency and euthanasia are examples of problems that clinicians frequently face today. PMID- 7992657 TI - [The Program of External Quality Evaluation in Clinical Chemistry. An overview and evaluation after 11 years of functioning]. AB - After an eleven-year period, the goals and way of functioning are remembered the External Quality Assessment Scheme in Clinical Chemistry, under the responsibility of the National Institute of Health. The authors try to evaluate the quality of results obtained at the time by the 160 participant laboratories, belonging to the public and private sectors as well as to the Portuguese reference laboratories which have to assign the expected values on the control sera to be analysed. As regards the 22 biochemical blood parameters, we came to the conclusion that there is a high performance level in what concerns the reference laboratories and a quality level of participant laboratories in accordance with their considered peer foreign laboratories. PMID- 7992658 TI - Hyaluronan in cerebrospinal fluid after head injury. AB - Hyaluronan (HYA) is a large molecular weight polysaccharide which functions in various roles throughout the body. Little is known regarding HYA in human cerebrospinal fluid (CSF). We measured CSF and serum HYA concentrations in eleven patients with varying degrees of head injury. In these patients, CSF HYA ranged from 46 to 772 micrograms/l and serum HYA from 16 to 573 micrograms/l. We did not find any relationship between HYA values in CSF or serum and underlying disease or Glasgow Coma Scale (GCS). The role of CSF HYA in the injured human brain has yet to be elucidated. PMID- 7992659 TI - An unusual neurological feature of HIV-1 encephalopathy: Gerstmann's syndrome. AB - The authors describe the first case in literature of Gerstmann's syndrome (agraphia, acalculia, finger agnosia) occurred in HIV correlated encephalopathy developed as the first severe manifestation of HIV infection in a patient with prevalent white matter neuroradiologic alterations. The PDL rapidly extended from the left subcortical parietal-occipital regions to the pre-rolandic one, with subsequent involvement of the corpus calosum splenium and the bilateral temporal lobes white matter. The authors indicate the extent of the lesions and the involvement of the interhemispheric connection fibres as the pathogenetic mechanism of the "Gerstmann syndrome", that until today has not been reported in the literature of the wide variety of AIDS dementia complex. The administration of 1 g of zidovudine for about 9 months did not avoid the establishing of the neurologic damage, but the sudden suspension of the drug could have enhanced the exacerbation of inflammation and the involvement of areas whose lesion is classically believed responsible for cognitive impairment. PMID- 7992661 TI - Giant basilar artery aneurysm associated with moya-moya disease. Case report and review of the literature. AB - The case of a 32-year-old man with a giant, partially thrombosed, basilar artery aneurysm associated with moya-moya disease is described. The patient exhibited symptoms due to compression of the aneurysm on the right cerebral peduncle. He was discharged after conservative treatment for 10 days. Pathogenesis and management of this rare case are discussed in the light of data reported from the literature. PMID- 7992660 TI - Imaging of inner cerebral trauma. AB - The concept of "Inner cerebral trauma" (ICT) has been preliminary defined as a characteristic topographic pattern of deep brain lesions produced by physical forces occurring within the cranial cavity in closed head injury of the acceleration/deceleration type. The lesions, based on neuropathological examinations, are characteristically localized in the "centro-axial" regions of the brain. The extent of ICT is often underestimated by CT. Due to assess the value of MR imaging, 83 patients with ICT were examined on a 1.5 T unit in different stages after trauma. The pattern of lesions, as shown with MR imaging, correlated well with neuropathological studies, suggesting a multifocal pathogenesis of severe traumatic brain injury. PMID- 7992662 TI - Chorea due to hyperthyroidism in old age. A case report. AB - The authors discuss the case of an elderly female patient with thyrotoxicosis and chorea. T3 and T4 serum values were high. Since the chorea disappeared with euthyroidism but reappeared whenever there was a further increase in T3 and T4, its relationship on hyperthyroidism and its reversibility are clearly demonstrated. The chorea therefore appears to be another clinical condition present in hyperthyroidism. PMID- 7992663 TI - Superficial hemosiderosis of the central nervous system. A case report. AB - A case of idiopathic superficial hemosiderosis (SH) of the central nervous system and a review of the literature are presented. The patient suffered from progressive cerebellar ataxia, hearing loss, anosmia, spastic paraparesis, but no mental deterioration. The diagnosis was made with brain and spinal MRI, that showed in T2 weighted images superficial hypointensity of spinal cord, medulla oblungata, pons, mesencephalon, cerebellum and cerebral hemispheres, images that are considered pathognomonic of SH. Repeated spinal fluid examinations were negative, suggesting that evidence of overt subarachnoidal bleeding is not essential in the diagnosis. In patients with SH of unknown etiology no valid therapy is yet available. PMID- 7992664 TI - Hand deformities in extrapyramidal disorders. AB - Hand deformities cause severe discomfort and functional limitations to patients with Parkinson disease (PD) and related disorders. In clinical practice the problem is often overlooked or misdiagnosed. This paper reports on four cases whose characteristics are discussed. PMID- 7992665 TI - Multiple sclerosis and Sjogren's syndrome. PMID- 7992666 TI - Interleukin-1 beta plasma secretion during diurnal spontaneous and induced sleeping in healthy volunteers. AB - We previously reported nocturnal plasma IL-1 beta (beta) increases during sleep in absence of stress-induced activation of hypothalamic-pituitary-adrenal (HPA) axis. In this paper we evaluate the presence of plasma IL-1 beta secretion in nine healthy volunteers (mean age 31.2 +/- 4.2) during post-prandial naps, after the administration of zolpidem, a benzodiazepine receptorial agonist. Although a significant increase in IL-1 beta plasma levels during spontaneous sleep was present in only four subjects when compared to those obtained during wake and induced-sleep, spontaneous sleep IL-1 beta mean plasma levels appeared slightly higher than both wake and induced-sleep values. Moreover, a negative correlation was present between IL-1 beta and cortisol (F) values obtained during the early afternoon (r = 7; p < 0.05). Our findings are consistent with a possible association of IL-1 beta secretion to physiologic sleep also during daytime spontaneous naps, with the presence of F influence on this phenomenon, and with the lack of IL-1 beta association to daytime naps after sleep-inducer pharmacological agents. PMID- 7992668 TI - Chronic and acute pain syndromes in patients with multiple sclerosis. AB - We have studied 122 patients (52 men and 70 women) with definite Multiple Sclerosis (MS) to evaluate the frequency and clinical characteristics of pain in MS. The Hamilton Rating Scale for depression, the Beck-Self Depression Inventory and the Kurtzke Disability Status Scale were used in all patients. We have divided the patients with pain in two groups: patients with pain syndromes at onset and patients with pain syndromes during the course of MS disease. We found that 57% of all our MS patients complained of pain syndromes at some time during the MS course, while 21% reported pain as a symptom at onset of MS. The majority of patients suffered from chronic pain (constant or intermittent pain lasting more than one month). The most frequent chronic syndromes were dysesthetic extremity pain, painful spasms and tonic seizures. We did not find a significant differences with respect to age, sex, disease duration, physical impairment, depressive symptoms between the patients of pain-free group and of pain groups. There was a significant difference in mean disease duration from diagnosis in patients reporting pain at onset of the disease. In conclusion, the pain in MS is not a rare symptom; the role of physiopathological mechanism underlying pain syndromes arise unclear. PMID- 7992667 TI - Primary antiphospholipid syndrome: two case reports, one with histological examination of skin, peripheral nerve and muscle. AB - Two cases of primary antiphospholipid antibody syndrome are reported. One patient presented multiple abortions and epilepsy. The second patient was affected by a brain vascular accident, with a residual hemiparesis. Both cases showed livedo reticularis in arms, NMR evidence of diffuse lesions of the white matter, high serum levels of anticardiolipin antibodies and cardiopathy. Lupus anticoagulant was also found in the serum of the first patient, and cortisone and antiaggregants enabled her to reach term in a fifth pregnancy after four miscarriages. In the other case histological examination of specimens of skin, peripheral nerve and skeletal muscle revealed occlusive, non arteriosclerotic vasculopathy and an absence of inflammatory lesions. Histological study has rarely been performed in primary antiphospholipid syndrome but suggests that the mechanism of thrombosis is not vascular; in our subjects it revealed findings similar to those in Sneddon syndrome. PMID- 7992669 TI - Putting restrained and unrestrained nondieters on short-term diets: effects on eating. AB - This study examined the joint effect of restrained eating status and short-term food restriction on ice cream consumption in the laboratory. Restrained and unrestrained eaters who were not dieting were asked to restrict their food intake for 2 days or to continue eating normally. They then engaged in an ostensible taste test of ice cream. A restraint x restriction interaction was found for ice cream consumption. Among unrestrained eaters, restricted subjects ate more than unrestricted ones; among restrained eaters, the opposite eating pattern was found. These results were attributed to the differential sensitivity of restrained and unrestrained eaters to the internal and external eating cues manipulated in the study. PMID- 7992670 TI - Effects of nicotine abstinence and menstrual phase on task performance. AB - Both menstrual phase and nicotine have been shown to affect task performance. Though conflicting results have been reported, at least one well-controlled study has demonstrated that women at midluteal phase show superior performance on speech articulation and speeded motor coordination tests, but poorer performance on perceptual-spatial tests, than during menses. Smokers have demonstrated superior performance on numerous tasks following nicotine than following placebo. To explore the separate and combined influence of these factors, we studied 13 regularly-menstruating smokers using a two (smoking vs. 12 hours' abstinence) by two (menstrual vs. midluteal phase) factorial design. During each session, subjects completed a test battery including two speeded motor coordination tasks, a computerized reaction time test, and the Stroop (1935) color/word test. Subjects completed the Stroop color and color-word tasks significantly faster after ad lib smoking than after overnight abstinence. No other significant differences emerged. Our findings replicate, in an all-female sample, previous reports that speed of cognitive processing is reduced by nicotine abstinence (or enhanced by nicotine administration). Our failure to observe menstrual cycle effects raises the possibility that the anti-estrogenic effects of smoking may attenuate phase differences in performance. PMID- 7992671 TI - Social influence predictors of alcohol use among New York Latino youth. AB - We examined demographic and social influence predictors of adolescent drinking among New York City Latino adolescents, including specific Latino subgroups (i.e., Puerto Rican, Dominican, Colombian, and Ecuadorian). Sixth- and seventh grade students (N = 3129) who identified themselves as Latino or Hispanic on the survey questionnaire comprised our Latino sample. The survey included self reported frequency of alcohol use, demographic items, and measures of social influences for drinking. Logistic-regression analyses revealed that social influences (how many friends drink, attitudes of parents and friends toward respondent's drinking) are strong predictors of current drinking (defined as drinking at least once a month) for the overall sample of Latino youth, as well as for Puerto Rican youth and Dominican youth. Findings are discussed in terms of their implications for prevention. PMID- 7992672 TI - Characteristics of alexithymia and eating disorders in college women. AB - This study examined the relationship between characteristics of alexithymia and eating disorders (anorexia nervosa, bulimia nervosa, and obesity) in a nonclinical sample of 308 college women. Scores on the Toronto Alexithymia Scale were mostly unrelated to a weight index, which assessed subjects' deviation from their expected weight, but were correlated with subjects' scores on the Eating Disorders Inventory (EDI). EDI scores were related to the affective deficits of alexithymia (difficulty identifying and communicating feelings), but not to the cognitive disturbance associated with alexithymia. PMID- 7992673 TI - Planning a spit tobacco cessation intervention: identification of beliefs associated with addiction. AB - We examine the relationship between beliefs regarding spit tobacco (ST) use and addiction among 473 male college athletes who currently use ST. Beliefs were assessed using methods prescribed by the Theory of Reasoned Action. Independent associations between beliefs and addiction, defined by self-reported amount of ST used per week, were found via multivariate polychotomous regression modeling. We found that with increasing addiction level, athletes were significantly more likely to believe that "ST helps me relax," "ST keeps me alert," "ST tastes good," and "ST is addicting." All athletes believed that clinicians, parents, and girlfriends do not approve of their ST use, but that male peers, coaches, and professional athletes are fairly indifferent about it. To increase quit rates, highly addicted ST users may require an intensive cessation program including nicotine replacement to overcome symptoms of withdrawal, oral substitutes for the enjoyable taste of ST, and the support of male peers and athletes who influence their social norms. PMID- 7992674 TI - Is sham smoking an adequate control condition for the motoric component of smoking? AB - This is a study of the similarities and differences between real and sham smoking; 15 participants, all of whom had a smoking history of more than two years, attended on two occasions within a balanced design. They were instructed to either smoke or sham smoke their own brand of cigarette as normally as possible. Real and sham smoking were highly correlated for various measures: frequency of puffs, puff duration, interpuff interval, puff volume, and puff pressure. This showed that the pattern of smoking was common across the two conditions. At the same time, there were differences between the two conditions in the intensity of smoking, such that sham smoking led to significant increases in puff duration, volume, frequency, and decreases in the length of interpuff interval. Sham smoking is often used in smoking experimentation as a control for various aspects of smoking. This is the first study to examine the commonalities between real and sham smoking in a detailed and systematic fashion. PMID- 7992675 TI - Food intake and physical activity: a comparison of three measures of dieting. AB - We examined food preferences, dietary intake, and physical activity in dieters and nondieters using three different methods of dieting classification. One hundred three women and 99 men completed the cognitive restraint subscale of Stunkard and Messick's (1985) Three Factor Eating Questionnaire (TFEQ-R) and Herman and Polivy's (1980) Restraint Scale (RS), and answered questions about their current efforts to lose or maintain weight. Women identifying themselves as currently dieting to lose weight reported expending twice as much energy in physical activity compared to those reporting that they were either currently dieting to maintain weight or not dieting. There were no significant differences in dietary intake or physical activity by current dieting status in men. Women chronic dieters identified by high TFEQ-R scores reported lower total calorie intake and less frequent sweets consumption than women with low TFEQ-R scores. In men, those with high TFEQ-R scores reported consuming a greater percent of calories from protein and carbohydrate, less beef, pork, whole milk, and sweets. In women, the RS did not distinguish dieters from nondieters on any measure. In men, the RS results were similar to those from the TFEQ-R. These results show that current measures of dieting are only weakly related to behaviors thought to be indicative of dieting. Future research must develop more precise measures of dieting in order to examine the relationship between self-reports of dieting and behaviors thought to be related to dieting. PMID- 7992676 TI - Prevalence, patterns, and correlates of spit tobacco use in a college athlete population. AB - We surveyed varsity athletes (N = 1,328) in 16 California colleges about their patterns of spit (smokeless) tobacco (ST) use, related habits, reasons for use, and preferred methods for quitting. Prevalence of use was analyzed by sport and demographic characteristics, and patterns of use in players using snuff exclusively, using chewing tobacco exclusively, and those using both were compared. Odds ratios and 95% confidence intervals were calculated, adjusting for ethnic group. Prevalence was highest in Whites (44%) and Native Americans (48%) and lowest in African Americans (11%), and higher in varsity baseball (52%) than varsity football players (26%), in players attending rural colleges, and among those who ever smoked cigarettes or used alcohol. Forty-one percent of ST users initiated regular use during their high school years. Athletes who used snuff exclusively used it more intensively and for more years than those who used chewing tobacco exclusively. Snuff users indicated a greater perceived need for ST, but also were more ready to quit. These data suggest ST programs with prevention and cessation components are appropriate for high school as well as college athletes. Such interventions should focus on baseball players, distinguish snuff from chewing tobacco users in planning quit strategies, integrate intervention programs for cigarette smoking and alcohol consumption, provide training in refusal skills, and attempt to change social norms in support of ST use by integrating popular peers and significant others (e.g., wives/girlfriends) to endorse nonuse of ST. PMID- 7992677 TI - Cognitive brain potential alterations in boys exposed to opiates: in utero and lifestyle comparisons. AB - Several studies have observed that intrauterine exposure to opiates results in emotional and cognitive complications for the child, but genetic and postnatal social-environmental factors may also affect the CNS development of these children. To assess the relative contribution of the in utero and social environmental (lifestyle) effects of opiate exposure, event-related potentials (ERPs) and performance were studied in three groups of 7- to 12-year-old boys: (1) the in utero/lifestyle group (IU/LS) contained 16 boys who were exposed to opiates (in utero and lived with opiate-abusing mothers, (2) the lifestyle group (LS) included 14 boys who lived with opiate-abusing mothers, and (3) the control group (CON) composed of 13 boys. The cognitive ERP components and task performance were recorded in the Auditory Rare Event Monitoring (AREM) task and the Sternberg Memory task (Sternberg, 1975). On the AREM and Sternberg Memory tasks, P200 component was significantly decreased for the IU/LS and LS groups. On the Sternberg Memory task, percent correct was also significantly impaired in IU/LS and LS groups. The ERP alterations in the boys living with opiate-abusing mothers with and without intrauterine opiate exposure were similar. A dysfunctional social environment may contribute to the cognitive deficits seen in the sons of opiate-abusing mothers. PMID- 7992678 TI - Teasing, body image, and self-esteem in a clinical sample of obese women. AB - This study examined the relationship of physical-appearance-related teasing history to body image and self-esteem in a clinical sample of adult obese females. The frequency of being teased about weight and size while growing up was negatively correlated with evaluation of one's appearance and positively correlated with body dissatisfaction during adulthood. Self-esteem was unrelated to teasing history but covaried significantly with body image measures. Subjects with early-onset obesity reported greater body dissatisfaction than did subjects with adult-onset obesity. The findings suggest that being teased about weight/size while growing up may represent a risk factor for the development of negative body image and that self-esteem and body image covary. PMID- 7992679 TI - Use of urine cotinine to validate smoking self-reports in U.S. Navy recruits. AB - Cotinine analysis of urine has been used by many researchers to determine validity of smoking self-reports. This technique is easy and inexpensive, but has not been used previously in military smoking studies. This study incorporated a random validation of self-reported smoking by U.S. Navy recruits participating in a smoking relapse program (N = 496). Results of cotinine analysis indicate only a 1% misrepresentation of actual smoking status. These results suggest smoking self reports from U.S. Navy recruits are very good indicators of actual smoking status. PMID- 7992680 TI - Hereditary metabolic cardiomyopathies. PMID- 7992681 TI - Idiopathic autoimmune thrombocytopenic purpura. AB - Childhood ITP occurs in acute and chronic forms. In general, both diseases are mild and can be managed conservatively. Approaches to therapy are highly controversial and vary widely among pediatricians and academic centers. Approximately 5% of children with ITP will develop chronic disease with severe thrombocytopenia and bleeding. These children require therapy, which is often expensive and not without risk of development of late adverse effects. PMID- 7992682 TI - Dysfunctional swallowing and respiratory disease in children. PMID- 7992683 TI - Henoch-Schonlein purpura. AB - Henoch-Schonlein purpura is a fairly common pediatric disorder. The role of immunosuppression in the treatment of HSP continues to be controversial and awaits a multicenter controlled trial. The prognosis for the majority of patients is very good. Less than 2% of patients develop a serious complication associated with long-term morbidity. The most common serious complication is end-stage kidney disease, which may develop late in the disease after the symptoms from other organ systems have resolved. Patients with HSP should be carefully followed for several years to look for evidence of late renal involvement, and those patients who develop renal involvement should be followed regularly throughout their lifetime. PMID- 7992684 TI - The persistent vegetative state in children. PMID- 7992685 TI - Advances in the treatment of precocious puberty. AB - The development of immunoassay techniques for accurately measuring serum gonadotropins and gonadal steroids allows distinction between central (GnRH dependent) and peripheral (GnRH-independent) precocious puberty in children. Previously (see case 3) it was not possible to do this, and a rational approach to therapy could not be designed. Significant advances in the synthesis of superagonists of gonadotropin-releasing hormone have allowed effective treatment for children with CPP. Such treatment has only been possible for the past 10 to 15 years, and GnRHa have been approved for use in the United States for this indication only since 1992. Long-term studies are still needed to determine what effect, if any, such treatment has on fertility, because only a few patients, even from the earliest studies, have reached child-bearing age. All indications, however, suggest that treatment with GnRHa is reversible, as well as safe and efficacious. More challenging is the effective treatment of PPP, for which innovative approaches involving inhibition of gonadal steroid synthesis or action have met with some success. Again, long-term studies or efficacy and safety are needed. PMID- 7992688 TI - Understanding diabetes in children. PMID- 7992687 TI - Fragile X syndrome. AB - 1. Fragile X syndrome is defined by the combination of a characteristic phenotype, cognitive impairment, the presence of a fragile site (gap) detectable in folate-free culture medium on Xq27.3 called FRA X A, and transcriptional inhibition, through overmethylation, of an mRNA protein-binding gene called FMR 1. 2. It is inherited in an atypical X-linked dominant way and affects about 1 in 1000 males and 1 in 2000 females; about 1 in 700 females is a carrier. 3. A characteristic but subtle phenotype includes an elongated face and mandible, large ears, macrocephaly with bizygomatic pinching, soft skin, inconsistent mitral valve prolapse, macroorchidism, mildly shortened stature in adulthood, and characteristic behavior that may resemble autism and attention deficit disorders. Intellectual impairment in affected individuals varies from mild to severe, with a majority of affected males within the moderate range of cognitive disability. Twenty percent of males with the mutation are phenotypically and intellectually unaffected. They ae called transmitting males. 4. Female heterozygotes may be indistinguishable from the general population, or they may have subtle physical signs or both physical and intellectual impairment. 5. Sensory motor integration is the therapy of choice for the learning disabilities in children with fragile X syndrome. The benefits of folic acid supplementation are equivocal. 6. A sensitive and understanding support system for the patient and extended family is an inseparable component of appropriate management of fragile X syndrome. 7. Molecularly the mutation is characterized by varying lengths of DNA fragments consisting of the trinucleotide CGG. It is repeated about 6 to 50 times in the normal population and approximately 51 to 200 times in unaffected individuals with a so-called premuation who are at risk for expansion and transmission to offspring. Individuals with over 200 repeats are usually affected and said to have a full mutation. 8. The physician caring for a family with fragile X syndrome should work with an experienced genetics center, counselor, and a laboratory with expertise. PMID- 7992686 TI - Menkes disease. PMID- 7992689 TI - Building an embryo with limited resources. PMID- 7992690 TI - The immunology of Kawasaki disease. PMID- 7992691 TI - Anaerobic infections in the neonate. PMID- 7992692 TI - Immunotherapy for infection and malignancy in children with cancer. PMID- 7992693 TI - Niemann-Pick disease: newer classification based on genetic mutations of the disease. PMID- 7992695 TI - Premature exfoliation of teeth in childhood and adolescence. AB - Although the premature loss of primary teeth in conjunction with early eruption may be of no clinical significance, the loss of primary or permanent teeth in the absence of trauma should not be overlooked by the clinician. Premature loss of teeth associated with systemic disease usually results from some change in the immune system or connective tissue. This chapter presented some conditions associated with loosening and/or premature loss of teeth that may be encountered in children and adolescents. The most common of these conditions appear to be hypophosphatasia and early-onset periodontitis. Other less common conditions were described to aid in forming a differential diagnosis. Other diseases that may manifest with severe oral infection, such as Wiskott-Aldrich syndrome, diabetes mellitus, or herpes zoster, could result in early tooth loss. PMID- 7992694 TI - Acquired immunodeficiency syndrome and the developing nervous system. PMID- 7992696 TI - Epilepsy surgery in children: state of the art. PMID- 7992697 TI - Radiofrequency catheter ablation of cardiac arrhythmias in pediatric patients. AB - Since their introduction 4 years ago in children, radiofrequency ablation techniques for definitive management of cardiac arrhythmias have evolved dramatically. All forms of abnormal tachycardia in children are now amenable to ablation. The success rates are high, and the procedure-related and short-term risks of ablation are very low. Radiofrequency ablation offers significant advantages over cardiac surgery as well as over long-term or lifetime administration of antiarrhythmic medications. The application of these techniques to children requires, in addition to experience in electrophysiology, a thorough knowledge of developmental issues in children, pediatric catheterization techniques, and a detailed knowledge of congenital heart disease. Although the impressive safety of the technique in the short term suggests that it should be considered as first-choice therapy for children with serious tachyarrhythmias, unresolved questions about the long-term safety of the technique suggest that a cautious approach should be taken in the application of radiofrequency ablation to the pediatric age group, and particularly in younger children and infants. PMID- 7992698 TI - [Experience of extravesical dismembered antireflux surgery]. AB - Thirty-eight patients (61 ureters) with primary vesicoureteral reflux who underwent extravesical antireflux surgery between Jan. 1975 and March 1989 were retrospectively analyzed. The overall postoperative vesicoureteral reflux (VUR) disappeared in 81.6% (31/38) of the patients, 86.9% (53/61) of the ureters. Among patients under 8 years old, VUR disappeared in all but one ureter. The postoperative VUR the disappeared in 95.7% (22/23) of the patients, 97.2% (35/36) of the ureters. Early postoperative early complications, including macrohematuria and bladder irritation were significantly fewer than those occurring in patients treated by the intravesical method. There were no serious late complications. Under restricted indications for patients under 8 years old, extravesical antireflux surgery might be clinically useful for treatment of VUR. Through the re-evaluation of length of submucosal tunnel, surgical outcome of this procedure might be improved. PMID- 7992700 TI - [Long-term results and complications of intravesical instillation of bacillus Calmette-Guerin for prophylaxis of bladder cancer recurrence]. AB - Since 1982, we treated 22 patients with superficial bladder cancer via intravesical bacillus Calmette-Guerin (Tokyo 172 strain) for prophylaxis against tumor recurrence. To determine the long-term efficacy and complications of BCG therapy, retrospective analysis was performed. The BCG therapy was initiated one to two weeks after complete transurethral resection of visible tumors. One hundred twenty mg or 80 mg of BCG suspended in 40 ml of 0.9% NaCl solution was instilled into the bladder once a week for 6 times, then monthly for 10 times. Of 22 patients, 10 tumor recurrences were recognized in 4 patients (mean followup 74 months). Recurrent free rate at 5 years was 78.5%. Common side effects were low grade fever and bladder irritability. Although these side effects were self limiting, 15 patients (68%) refused instillation of BCG before completion of our protocol because of the bladder irritation. No relationship was observed between total dose of BCG instilled and tumor recurrence. Severe side effects such as permanent structural or functional alterations of the bladder or mycobacterial infection of other organs were not observed. Intravesical administration of Tokyo 172 strain of BCG seemed to be safe and useful for long-term prophylaxis of superficial bladder cancer recurrence. PMID- 7992699 TI - [Membranous and penile urethral involvement in bladder cancer patients-- review of cystoprostatourethrectomy specimens]. AB - We studied 18 cystoprostatourethrectomy specimens, which were surgically removed for bladder cancer and step-sectioned in 0.5 cm thickness, to evaluate the relationship of the membranous and penile urethral lesions, with the multiplicity of bladder cancer, association of carcinoma in situ (CIS), bladder neck involvement, and prostatic involvement. Thirteen cases were associated with CIS. There were four solitary bladder cancers and 14 were with multiple cancers. Twelve cases were with bladder neck involvement and seven with prostatic involvement. There were five cases of urethral involvement; two cases of CIS and three with dysplasia. No macroscopic urethral cancers were detected in the urethra. Four of the five cases of urethral involvement had multiple cancers with CIS and were associated with bladder neck and prostatic involvement. One case of urethral dysplasia had solitary bladder cancer and neither bladder neck nor prostatic involvement were observed. Statistical analysis revealed that prostatic involvement was the only significant risk factor for urethral involvement. Our study shows that bladder cancer patients with prostatic involvement should be excluded from the candidates for bladder substitution utilizing the retained urethra. When a neobladder is indicated to bladder cancer patients, each case should be followed carefully for urethral recurrence. PMID- 7992701 TI - [Six cases of upper urinary tract diseases including tumors and inflammatory lesions which suggest the significance of urine cytology in preoperative diagnosis]. AB - We present six cases of upper urinary tract diseases including tumors and inflammatory lesions in which the urine cytology rather than the radiological examinations was useful for their preoperative diagnoses. Three of the six cases had malignant diseases and the others had benign diseases. In all cases preoperative results of urine cytology were identical to histopathological findings of resected specimens; the cases with positive findings in urine cytology had ureter cancers and those with negative findings had benign diseases. Primary CIS of upper urinary tract was found in two of six cases, which is still uncommon in Japan. Since it is very difficult to make a preoperative diagnosis of primary CIS by radiological examinations, the present study showed that urine cytology is useful for its preoperative diagnosis. Recently endoscopic techniques for the diagnosis of upper urinary tract tumors are in clinical use. The ureteroscopic biopsy is recommended for the case in which the diagnosis using urine cytology is difficult. PMID- 7992702 TI - [A case of hydronephrosis caused by renal stones with elevated serum levels of CA 19-9 and CA-125]. AB - A case of hydronephrosis caused by renal stones with elevated serum levels of carbohydrate antigens 19-9 (CA-19-9) and 125 (CA-125) is reported. A 74-year-old woman was hospitalized with pyelonephritis. The results of computerized tomography and endoscopy suggested that the patient did not have pancreatic or ovarian cancer, but laboratory tests were significant for serum CA-19-9 greater than 1,000 U/ml (normal less than 37) and serum CA-125 78 U/ml (normal less than 35), which are markers for such tumors. Abdominal X-ray films showed stones in the pelvis of the right kidney. Excretory urography showed that the right kidney was not functioning. Computerized tomography showed severe right hydronephrosis with a thin renal cortex. Complete obstruction of the ureteropelvic junction of the kidney was seen by retrograde pyelography. During percutaneous pyelography, aspiration of the pelvic urine was done, and the sample had a high concentration of CA-19-9 (250,000 U/ml), but no cancer cells. The patients underwent right nephrectomy. The pelvic urine was tested for both CA-19-9 and CA-125 this time, and both were high (190,000 U/ml and 5,100 U/ml, respectively). Pathological evaluation showed no evidence of a malignant tumor. The epithelium lining the renal pelvis was stained for both CA-19-9 and CA-125 using the avidin-biotin peroxidase complex method. Serum levels of the markers returned to normal after nephrectomy. PMID- 7992703 TI - [A case of retrovesical hemangiopericytoma]. AB - A case of retrovesical hemangiopericytoma is reported. The patient was a 44-year old woman with right lumbago. Cystoscopy showed extra-vesical compression in the area from the trigone to right wall of bladder. The histological examination of the specimen obtained with ultrasound-guided transvaginal biopsy revealed hemangiopericytoma. Because of the invasion to the bladder mucosae, total cystectomy and ileal conduit were performed. The patient received postoperative irradiation of 3,060 rad for pelvis. Eight months after operation, computerized tomography showed no evidence of local recurrence of the tumor. PMID- 7992704 TI - [Persistent mullerian duct syndrome: report of two cases]. AB - Persistent Mullerian duct syndrome is characterized by the retention of mullerian derivatives in patients otherwise normally virilized. Clinically, the persistence of uterus and tubes leads either to cryptorchidism or inguinal hernia. The condition is usually discovered at surgery. We report two boys with this anomaly. In each case, hysterectomy and orchidopexy were carried out. The gonads were testes and the karyotype was 46, XY. Long-term follow up for these patients is necessary because of an increased risk of testicular tumors and infertility which will develop in future. PMID- 7992705 TI - [A case report of condyloma acuminatum in female urethra]. AB - A case of condyloma acuminatum in female urethra is reported. A 53-year-old woman was referred to our clinic because of urethral bleeding. A tumor was noted around the external urethral meatus and the size of the tumor was 20 mm in diameter. Excision was performed on the tumor including the external urethral meatus. Pathological examination revealed condyloma acuminatum. Condyloma acuminatum in female urethra is very rare. We reviewed and discussed 6 cases of condyloma acuminatum in female urethra, including our case, in the Japanese literature. PMID- 7992706 TI - [A case of metachronous bilateral malignant lymphoma of the testis]. AB - We report a case of metachronous bilateral malignant lymphoma of the testis. A 67 year-old man was admitted to our hospital with complaints of left scrotal swelling with swelling of the left inguinal lymph node. Left high orchiectomy and dissection of the left inguinal lymph node were done under the diagnosis of the testicular tumor. Histopathological diagnosis was non-Hodgkin's lymphoma of diffuse, medium-sized cells of the B cell type. Several examinations revealed no apparent additional involvement. Chemotherapy was initiated with cyclophosphamide, adriamycin, vincristine and prednisolone (VEPA). One year and 10 months later, contralateral right scrotal swelling with swelling of the right inguinal lymph node occurred. Histopathological findings were similar to those of the resected left testis. We discussed malignant lymphoma of the testis, especially bilateral cases. PMID- 7992707 TI - [Management of advanced urogenital cancer: treatment of metastasis]. AB - In clinical trials in advanced urogenital cancer with metastasis there are cases showing a poor clinical response and poor prognosis. The cure of advanced urogenital cancer still remains a major problem in management. The present paper is a summary of 8 articles presented at the symposium on "Management of advanced urogenital cancer: Treatment of metastasis" in the 43th Annual Meeting of Center Section of Japanese Urological Association in November, 1993. The present status, problems and future conception of treatment modalities for advanced urogenital cancer were discussed. PMID- 7992708 TI - [Role of organ specific fibroblasts in metastasis of human renal cell carcinoma: regulation of type IV collagenase production from human renal cell carcinoma by organ specific fibroblasts]. AB - An orthotopic metastatic human renal cell carcinoma model in nude mice was established to evaluate the mechanism of metastasis as a preliminary phase in the development of a treatment to prevent cancer metastasis. The effect of host fibroblasts from different organs on the production of type IV collagenase by human renal cell carcinoma and the factors which influenced the enzyme production and secretion by fibroblasts were also investigated. KG-2 cells were established from human renal cell carcinoma, and produced tumors following implantation to both the subrenal capsular space (orthotopic site) and subcutis (ectopic site). Histologically, the tumors in the subcuit (SC tumors) were well encapsulated with a thick fibrous capsule and did not produce metastasis or invasion, whereas those in the subrenal capsular space (SRC tumors) lacked a fibrous capsule and produced metastasis at the lung or regional lymph nodes. The production of type IV collagenase in conditioned media from metastatic SRC tumors and lung metastatic lesions was larger than that from non-metastatic SC tumors. The conditioned media separated from mouse kidney or lung fibroblasts stimulated the production of type IV collagenase by KG-2 cells, whereas, that separated from mouse skin fibroblasts decreased the enzyme production. The production of type IV collagenase by KG-2 cells was stimulated by cocultured KG-2 cells and fibroblasts from the kidney or lung, whereas it was suppressed by cocultured KG-2 cells and skin fibroblasts.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7992709 TI - [Management of advanced renal cell carcinoma: surgical treatment of metastasis]. AB - The prognosis of advanced renal cell carcinoma, especially with metastatic lesions was very poor. We described the outcome of surgical treatment of advanced renal cell carcinoma with metastasis. From 1964 to 1992, 279 cases of renal cancer were treated in the Department of Urology, the Center for Adult Diseases, Osaka. Sixty four cases were with distant metastasis (M1 case) and 55 cases were recurrent after radical nephrectomy (M0-M1 case). Among these 119 cases with distant metastasis, 50 cases were treated by surgical resection. Indication of surgical resection was first to obtain surgical complete regression (sCR), second to improve quality of life (QOL). Lung metastases from 14 patients (M1, 5 cases; M0-M1, 9 cases) were resected. The survival of patients with unilateral lung metastases was significantly better than that of patients with bilateral lung metastases. Bone metastases from 18 patients (7 cases to obtain sCR, 11 cases to improve QOL) were resected. The prognosis of patients with bone metastasis was very poor, and more than a 3-year survival was seen in only patients histopathologically with grade 1. QOL improvement was observed in 9 of 11 patients (82%). Solitary adrenal metastasis showed a relatively good prognosis. Surgical resection of brain metastasis was performed only to improve QOL, because all patients had other metastases. Lymph node metastasis showed in general poor prognosis. Six cases with tumor thrombus extending into inferior vena cava nephrectomized under extracorporeal circulation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7992710 TI - [Intraarterial chemotherapy for metastatic renal cell carcinomas: combination with MDR-overcoming agents]. AB - We analyzed the sensitizing activity of five agents, which have been assumed to be MDR-overcoming drugs, in two human renal cell carcinoma cell lines expressing the MDR1 gene at high levels. In addition, we studied the sensitizing activity of cepharanthin, an MDR-overcoming agents, to vinblastine, adriamycin, epirubicin, cisplatin, mitomycin C and etoposide. Based on the results, we treated 6 patients with metastatic renal cell carcinomas (4: bones, 2: contralateral kidneys) by intraarterial injection of vinblastine and adriamycin (or epirubicin) in combination with cepharanthin. Two of the 4 bone metastasis cases responded markedly to the treatment. Renal tubular impairment was observed in one patient who was treated for the contralateral kidney metastasis. PMID- 7992711 TI - [Treatments for advanced transitional cell carcinoma of the urinary tract: chemotherapy and operation]. AB - The current status of treatments for advanced transitional cell carcinoma of the urinary tract with metastasis is reported. A total of 62 patients were treated in Nara Medical University Hospital and its affiliated hospitals between January, 1980 and June, 1993. All patients were divided into two categories; cases in which local recurrence and/or distant metastasis had developed during the followup study (group 1) (n = 32) and fresh cases with distant metastasis (group 2) (n = 30). Most of the metastatic sites were treated with chemotherapy alone or combination therapy including chemotherapy. As for clinical response of each case, CR + PR rate in group 1 (34%) was higher than that in group 2 (13%) (p < 0.1). As for prognosis, the survival rate in group 1 was significantly higher than that in group 2 (p < 0.05). In group 1, the survival of CR was significantly higher than that of the non-responders. No adjuvant therapy for invasive bladder cancer and post-operative adjuvant therapy for renal pelvic and/or ureteral cancer can be recommended to prevent local recurrence or distant metastasis. In addition, supporting therapy and dose intensified chemotherapy would lead to good prognosis in advanced urothelial cancer patients. PMID- 7992712 TI - [Treatment of advanced prostate cancer]. AB - The treatment against hormone relapsing prostate cancer was examined clinically, experimentally and by a review of the literature. Conventional systemic chemotherapy should be appreciated as one of the symptomatic treatment options; and suramin might be an effective chemotherapeutic agent, if severe and the wide spectrum of side effects were concurred. Intermittent administration of suramin is beneficial at present, with monitoring of its concentration in the blood. Some patients with wide spread bone metastases, especially if they are symptomatic, would be the candidates for hemiskeletal irradiation. Low dose of fractionated radiation was found to be more effective than high dose of single radiation. Bisphosphonate was found to protect bone resorption and destruction from the inoculated prostatic cancer cells in nude mice. In the clinic, the compound would be effective to the aggravation of bone metastasis, especially in combined use with irradiation. PMID- 7992713 TI - [The role of salvage surgery following chemotherapy in advanced testicular cancer]. AB - Twenty-seven patients with advanced testicular cancer underwent cisplatin-based combination chemotherapy and followed by salvage surgery. Complete necrosis and/or fibrosis (necrosis) was found in 12 (44%) operative specimens, mature teratoma in 5 (19%) and residual cancer in 10 (37%) patients. Ten of the 12 (83%) patients with necrosis and all 5 with mature teratoma were rendered disease-free (NED). Only 6 of the 10 (60%) patients with residual cancer were continuously NED. These findings suggest that if carcinoma is found in the resected specimen, further salvage chemotherapy is required. Salvage surgery should be avoided in patients with elevated serum tumor marker levels. PMID- 7992714 TI - [Retroperitoneal lymph node dissection for patients with advanced testicular tumor]. AB - We examined the indication for retroperitoneal lymph node dissection (RPLND) for 30 patients with advanced testicular tumor and made the following conclusion. The sequence of RPLND and primary chemotherapy made no difference in the therapeutic effect for patients with stage II A non-seminomatous germ cell tumor (NSGCT). However, we thought it better to administer primary chemotherapy prior to RPLND to prevent dissemination of tumor cells. Viable tumor cells often remained in retroperitoneal residual tumors even after chemotherapy in the patients with NSGCT advanced beyond stage II B. Therefore, RPLND seemed to be necessary if residual retroperitoneal tumors were found after the chemotherapy. In patients with seminoma, RPLND did not seem to be necessary if the residual tumor was less than 3 cm in diameter or the reduction rate of the retroperitoneal tumor was more than 80% after the initial therapy (chemotherapy or irradiation therapy. PMID- 7992715 TI - Eugene W. Caldwell Lecture. Technology: the key to controlling health care costs in the future. AB - The American health care financing system is in a state of crisis. The rising cost of health care and the progressive difficulty Americans are experiencing in accessing the system have produced a great national debate concerning the future of medicine in America. Current health care cost trends, which are not sustainable, are projected to consume 37% of the gross national product by the year 2030. The financing system that supports the health care system is failing. The number of uninsured residents is growing more than twice as fast as the number with health insurance. The legitimate concern about the spiraling cost for medicine has focused attention on seeking root causes. Critics have focused on technology as the single most important factor in driving the cost trends in medicine upward. They have concluded that "long-term control of the rate of increase in expenditures requires that we curb the development and diffusion of clinically useful technology." These critics have not made their case, because they base their conclusions on hospital-derived data. These data are inaccurate because of the phenomenon of "cost-shifting." The critics do not examine the important issue of productivity and do not have reliable data on the costs and benefits of new technologies. Finally, the critics do not take into account the issue of use and abuse of technology. This is particularly important in the ambulatory environment. To break the health care cost spiral, radiologists, as the keepers of new technology, must commit themselves to at least four fundamental initiatives. The current American hospital-based health system must be replaced with an ambulatory system; productivity must be the primary business goal for radiologists; pricing of new services should reflect actual resources consumed, not the in-patient services displaced; and radiologists must reassert their role as doctors' doctors. The health care cost spiral is a real national crisis. The mission for radiology is to introduce the minimally invasive, ambulatory system of the future. The costs for delivering care within the new system will be a fraction of former costs. My assignment is to present a perspective on the role radiology must play in introducing new imaging technology to medicine. One of the distinguishing features of American society is its fascination with technology. It is only natural that the American health care system reflects this orientation. PMID- 7992716 TI - Laparoscopic general surgery: current status and future potential. AB - In the 1990s, a sweeping change has occurred in general surgery driven by patients demanding cosmetically appealing incisions and speedier recuperation. Established surgeons have swarmed to academic and industry-sponsored courses to learn basic laparoscopic techniques. Hospitals have been forced to redesign operating suites and retrain nurses to keep pace with the technological changes. Industry has responded to powerful market forces with new high-tech equipment and a substantial investment for research and development. More and more, surgeons are collaborating with gastroenterologists, sonographers, and interventional radiologists with the hope of advancing minimally invasive surgical techniques. This article highlights the current status of laparoscopic surgery in the United States and foretells exciting advances for the future [1]. PMID- 7992717 TI - The radiologist's role in the new era of laparoscopic general surgery. PMID- 7992718 TI - The job market for radiology residents and fellows graduating in 1994. AB - OBJECTIVE: In response to anecdotal reports of grave deterioration in the job market for graduates of radiology training programs, the American College of Radiology undertook a systematic appraisal of this job market for 1994. MATERIALS AND METHODS: Between mid-April and mid-May 1994, the American College of Radiology surveyed 40 directors of randomly chosen diagnostic radiology training programs and 20 directors of randomly chosen radiation oncology training programs. We achieved a response rate of 80% or more in both categories. The survey asked, among other questions, the number of graduates, how many had jobs, the number of offers received by graduates this year and last, and how difficult the job market was relative to recent years. RESULTS: Directors reported that 96% of graduating residents and 86% of graduating diagnostic fellows had commitments for positions. Of those with commitments, 94% of residents and 84% of diagnostic fellows were reported to have jobs that reasonably matched their training and job goals. Program directors estimated that the average graduate received two job offers but, on average, rated the job market as somewhat more difficult than was typical of recent years and reported that 1993 graduates had received more job offers. Plans to change size were reported for one fourth of programs, but the job market situation was not an important reason for these planned changes. CONCLUSION: Although the overwhelming majority of 1994 graduates obtained jobs, and these overwhelmingly were jobs of interest, program directors reported that the job market was weakening. Given the changes in the socioeconomic environment- managed care, for example--and the changing job market, training programs should give more attention to the job market in planning for changes in size. PMID- 7992719 TI - Diagnosis and treatment of nephrolithiasis: current perspectives. AB - Urinary stones are a frequent cause of morbidity in persons in affluent industrialized societies. The surgical management of symptomatic stones in the upper urinary tract has changed dramatically in the past generation, largely because of the introduction of progressively less invasive treatment techniques. The concurrent revolution in radiologic imaging and interventional techniques has mirrored the surgical experience. This article reviews the current diagnosis and therapy of nephrolithiasis. An evaluation of the complex metabolic abnormalities present in the population of patients with urolithiasis is beyond the scope of this article, but several good reviews of this subject have been published recently [1-4]. Because primary urolithiasis involving the bladder or urethra is less common and is a separate medical entity, this article is focused on renal and ureteral calculi. PMID- 7992720 TI - Current perspectives in the diagnosis and treatment of urinary stone disease. PMID- 7992721 TI - CT of the acute abdomen: findings and impact on diagnosis and treatment. AB - An acute abdomen is a clinical condition characterized by severe abdominal pain that develops suddenly over several hours or less [1]. Abdominal tenderness and rigidity, either generalized or localized, usually are severe and indicate an urgent need for prompt diagnosis and treatment. The underlying cause of acute abdomen varies, and some cases require immediate surgical treatment, whereas for others, surgery is unnecessary or contraindicated. This need for prompt diagnosis and treatment should not preclude an appropriate investigation to establish the precise diagnosis before undertaking surgery [1, 2]. PMID- 7992722 TI - CT during arterial portography for the preoperative evaluation of hepatic tumors: how, when, and why? AB - CT during arterial portography (CTAP) is the most sensitive technique for the detection of intrahepatic tumors. CTAP is based on portal enhancement of the liver by infusion of contrast material through the superior mesenteric artery. This technique provides clear delineation of intrahepatic vessels, allowing segmental location of tumors to be accurately determined and relationships between tumors and intrahepatic vessels to be assessed. CTAP must be limited to patients for whom noninvasive preoperative imaging examinations have shown a potential for hepatic resection. In the majority of the cases, CTAP is performed in patients with hepatic metastases from colorectal cancer, but other types of tumor (either primary or secondary) may be an indication for CTAP. Visualization of nontumorous perfusion defects is a limitation of this technique, but such defects have been well described and have characteristic locations and appearance. In difficult cases, correlation with sonographic, CT, and MR imaging findings helps characterize portal perfusion defects. CTAP data can be viewed as multiplanar and three-dimensional reconstructions that allow preoperative planning of the extent of resection and determination of the volume of the remaining liver. The use of spiral CT shows promise in the performance of CTAP. PMID- 7992723 TI - Detection of pooled secretions above endotracheal-tube cuffs: value of plain radiographs in sheep cadavers and patients. AB - OBJECTIVE: Mechanical ventilation is thought to increase the risk of nosocomial pneumonia by permitting leakage of bacteria-laden gastro-oropharyngeal secretions into the upper airways. The goal of this study was (a) to validate radiographic signs of pooled secretions above endotracheal-tube cuffs (supracuff liquid) in an animal model and (b) to determine whether suctionable pooled supracuff liquid can be identified on bedside radiographs of intubated patients. MATERIALS AND METHODS: Diagnostic criteria for supracuff liquid were initially validated by three radiologists interpreting 162 randomized radiographs made in an intubated sheep cadaver. The primary criteria included (a) replacement of the normal supracuff lucency with liquid opacity and (b) the formation of a sharp interface between the lucency of the upper edge of the cuff below and the liquid above. Graded infusions of 0, 3, 8, 13, and 23 ml of saline were made in triplicate into the space above the cuff, and radiographs were evaluated for the presence or absence of saline. The validated diagnostic criteria were used by two radiologists to estimate the frequency with which pooled liquid was seen on portable chest radiographs of 47 patients undergoing elective short-term postanesthetic mechanical ventilation. RESULTS: In the sheep-cadaver model, the diagnostic criteria for supracuff liquid allowed successful differentiation between no liquid, a small amount of liquid (3-8 ml), and a large amount of liquid (13-23 ml; c2, p < .0001). In a clinical study, radiographic signs of supracuff liquid were identified in 57% of 47 patients. In a small subset of patients (n = 18), the estimated liquid volume (mean +/- SEM) was calculated to be 7.8 +/- 1.1 ml (range = 2.1-18.4 ml). CONCLUSIONS: Radiography is a sensitive means of identifying small volumes of supracuff liquid above the inflated cuffs of endotracheal tubes. Potentially contaminating liquid pooled above the cuff of an endotracheal tube can be identified in about half of patients undergoing short term mechanical ventilation. Our results suggest the suction of the supracuff space may be a reasonable prophylactic maneuver against nosocomial pneumonia. A much larger study is suggested to investigate the actual relation between pooled supracuff liquid and the development of nosocomial pneumonia. PMID- 7992724 TI - Thoracostomy tubes after acute chest injury: relationship between location in a pleural fissure and function. AB - OBJECTIVE: The purpose of this study was to determine how often chest tubes placed for acute trauma lie within a pleural fissure and to determine whether an intrapleural location influences outcome. SUBJECTS AND METHODS: Fifty-eight consecutive thoracostomy patients who had 66 chest tubes were studied prospectively. Tube location was determined from frontal and lateral chest radiographs. Outcome measures recorded included the following: duration of thoracostomy drainage, quantity of pleural fluid drained, need for further tubes, length of hospital stay, appearance on last chest radiograph before discharge, and need for surgical intervention. RESULTS: Thirty-eight (58%) of the tubes were placed within a pulmonary fissure, 15 (23%) were posterior, nine (13%) were anterior, and four (6%) were in other locations. We found no significant difference in any of the outcome measures between tubes located in the fissure and other tubes. CONCLUSION: A large percentage of tubes placed for acute chest trauma lie within a pleural fissure. These tubes, however, appear to function as effectively as those located elsewhere in the pleural space. PMID- 7992725 TI - Plain film radiography of the chest: findings that simulate pulmonary disease. AB - Many pitfalls are encountered while interpreting routine radiographs of the chest. Intrathoracic disease can be mimicked by disease or anatomic variation of the superimposed bony thorax and soft tissues, by artifacts, and by iatrogenic intrathoracic changes. Although cross-sectional imaging may occasionally be necessary to solve a problem case, most often the simple use of an additional projection such as a lordotic, kyphotic, oblique, or skin marker view is sufficient to exclude pulmonary disease. We illustrate a series of cases in which serious intrathoracic disease was mimicked by extrapulmonary processes. The correct interpretation of these findings in a timely manner with relatively simple and inexpensive maneuvers can save the patient unnecessary worry and expense. PMID- 7992726 TI - Atypical and unusual calcifications of the heart and great vessels: imaging findings. AB - Cardiovascular calcifications in the thorax may be clinically significant and may prove extremely valuable diagnostically. The typical appearance and location of common cardiovascular calcifications have been well described [1, 2]. We present a series of radiologic findings in patients with atypical and unusual cardiovascular calcifications in the thorax. PMID- 7992727 TI - Retroperitoneal schwannoma. PMID- 7992728 TI - Sonographic features of mediastinal tumors. AB - Although mediastinal sonography, thus far, is used rarely in the United States, it might play a role in the diagnostic workup of mediastinal pathology as an adjunctive examination technique to other imaging studies (chest radiography, CT, and MR imaging). Mediastinal sonography is an effective and inexpensive imaging method, with a higher sensitivity than conventional radiographs, for the detection of mediastinal tumors [1-3]. The diagnostic advantage of mediastinal sonography over chest radiography results from its capability to demonstrate deep central mediastinal lymph nodes sonographically long before a displacement of pleuromediastinal lines occurs [3]. Mediastinal sonography is inferior only marginally to CT in the detection of supraaortic, pericardial, and prevascular lesions (sensitivity, 98-100%), but certain compartments (e.g., the posterior mediastinum and the paravertebral region) can be evaluated only with CT or MR imaging [3]. In addition to the assessment of size and topographic characteristics of mediastinal masses, sonography precisely visualizes the internal structure of the tumor, which may suggest a specific diagnosis when considered along with the clinical presentation and the location of the tumor [4]. This article illustrates the sonographic appearance of various mediastinal tumors. PMID- 7992729 TI - Disappearing pulmonary metastases from a pineal teratoma. PMID- 7992730 TI - Coronary artery interposition graft simulating pseudoaneurysm of the ascending aorta on CT. PMID- 7992731 TI - Breast thickness in routine mammograms: effect on image quality and radiation dose. AB - OBJECTIVE: The purpose of this study was to compare the thickness of the compressed breast between mediolateral oblique and craniocaudal mammograms and to relate these differences in thickness to image quality and radiation dose. These differences may partially explain why some subtle tumors are better visualized on the craniocaudal view. SUBJECTS AND METHODS: The study population consisted of 250 paired mediolateral oblique and craniocaudal mammograms obtained on one mammographic unit by seven certified mammography technologists during a 2-month period. Only women with breast implants, prior lumpectomy and radiotherapy, or chest wall deformity were excluded. The digital readout of compressed breast thickness and applied compression force was recorded. Mammographic positioning was assessed using standard criteria. Absorbed radiation dose at different thicknesses was measured with a BR-12 breast phantom. Image quality differences for geometric unsharpness and contrast were calculated for the observed breast thickness differences between mediolateral oblique and craniocaudal mammograms. RESULTS: The mean thickness of the compressed breast on the craniocaudal view was less than the mean thickness on the mediolateral oblique view (4.4 versus 4.8 cm, p < .0001) despite the greater force used to compress the breast for mediolateral oblique than for craniocaudal views (93 versus 86 newtons, p < .0001). The breast thickness on the mediolateral oblique view exceeded that on the craniocaudal view in 98 (84%) of 117 pairs that differed in thickness by 5 mm or more and 46 (94%) of 49 pairs that differed by 10 mm or more (p < .0001). Geometric unsharpness increased by 8% and 19% when a 4.4-cm-thick breast was compared to a 4.8- and 5.4 cm-thick breast, respectively. A 5% and 12% loss of contrast was noted when a 4.4 cm-thick breast was compared to a 4.8- and 5.4-cm-thick breast. Mean glandular radiation dose at 4.4, 4.8, and 5.4 cm was 1.40, 1.70, and 2.33 mGy, respectively. CONCLUSION: The compressed breast is 8% thicker on mediolateral oblique than on craniocaudal mammograms, a small but statistically significant difference. This difference results in a small loss of spatial and contrast resolution on the mediolateral oblique views and an increase in radiation dose. These image quality differences may partially explain why some subtle carcinomas are better visualized on the craniocaudal view. PMID- 7992732 TI - Diffuse small-bowel ischemia in hypotensive adults after blunt trauma (shock bowel): CT findings and clinical significance. AB - OBJECTIVE: The purpose of this study is to describe CT findings of shock bowel (diffuse abnormality of the small bowel observed in hypotensive or hypoperfused patients after blunt abdominal trauma) and to determine the clinical significance of CT-diagnosed shock bowel. MATERIALS AND METHODS: A data base search of a radiology data registry indicated 13 patients had CT scans obtained at admission that showed diffuse abnormalities of the small bowel and a corresponding medical history of profound clinical shock preceding CT study. All patients sustained blunt abdominal trauma: nine were involved in motor vehicle collisions, three were struck by motor vehicles, and one had a crushing injury. Vehicular impacts were typically high speed, inducing multisystem injury. Admission and follow-up CT studies were reviewed to characterize and assess the evolution of the abdominal CT findings that occur with shock bowel. Medical records were reviewed to determine blood pressure at the accident scene or on admission, surgical findings, and patient outcome. RESULTS: All patients were severely hypotensive in the field or on admission; three were in cardiac arrest at the scene of the accident. CT scans showed diffuse thickening of the small-bowel wall in all patients, ranging from 7 mm to 15 mm (mean, 11 mm); fluid-filled, dilated small bowel in nine patients; subjectively increased contrast enhancement of the small bowel wall in six patients; and a flattened inferior vena cava (< 9 mm anteroposterior diameter at renal veins) in 10 patients. The colon appeared normal in all cases. Celiotomy in eight patients revealed normal-appearing small bowel by inspection in two and localized bowel injuries, with the remaining bowel appearing normal in six. Three patients, including one who had celiotomy, had normal-appearing small bowel on repeat CT scans obtained within 5 days of admission, and three had no clinical evidence of small-bowel disease. Three patients died of causes unrelated to bowel pathology. CONCLUSION: In trauma patients with hypotension, early abdominal CT may show diffuse abnormalities of the small bowel due to prolonged hypoperfusion--shock bowel--with a normal appearing colon. In this study, the CT findings of shock bowel were reversible and were not associated with clinical symptoms. PMID- 7992733 TI - Enteroclysis in the evaluation of obscure gastrointestinal bleeding. AB - OBJECTIVE: The diagnostic yield of enteroclysis was retrospectively evaluated for patients with obscure bleeding from the gastrointestinal tract. MATERIALS AND METHODS: A total of 128 patients with obscure gastrointestinal bleeding were referred to our department for enteroclysis between 1988 and 1993. The original radiologic reports were reviewed to determine the radiographic findings in these patients. The radiographic findings then were correlated with medical, surgical, and pathologic findings. RESULTS: Thirty-two patients had lesions found at enteroclysis. Nineteen of those patients had confirmation of the radiographic diagnosis, primarily by pathologic examination of the surgical specimen. Five other patients were found at surgery to have had false-positive diagnoses at enteroclysis. Eight patients ceased to bleed without pathologic corroboration, but their clinical presentation and course supported the radiographic diagnosis. Thus, 27 (21%) of the 128 patients had confirmed or highly probable lesions seen at enteroclysis as the cause of obscure gastrointestinal bleeding. Seventeen patients (13%) had tumors involving the small bowel, and three (2%) had arteriovenous malformations in the jejunum. CONCLUSION: This study corroborates earlier reports that enteroclysis is a useful diagnostic test for examining the small intestine in patients with obscure gastrointestinal bleeding. PMID- 7992734 TI - CT of the liver in patients with metastatic breast carcinoma treated by chemotherapy: findings simulating cirrhosis. AB - OBJECTIVE: Although the hepatotoxic effects of systemic chemotherapy are well known, CT findings in the liver after systemic chemotherapy have received little attention in the literature. In some patients with breast carcinoma metastatic to the liver who have received chemotherapy, a morphologic pattern develops similar to that associated with cirrhosis. This pattern is characterized by a lobular hepatic contour, segmental volume loss, and enlargement of the caudate lobe. The purpose of this study was to describe the CT appearance of this pseudocirrhosis and to correlate it with pathologic findings. MATERIALS AND METHODS: We reviewed 65 CT examinations of 22 patients with stage IV breast carcinoma with hepatic metastases, who were receiving systemic chemotherapy and for whom abdominal CT scans showed pseudocirrhosis. Nineteen of 22 patients had follow-up CT scans at intervals ranging from 1 to 15 months. Criteria for the diagnosis of pseudocirrhosis included a lobular hepatic contour, segmental volume loss, and enlargement of the caudate lobe. CT findings were correlated with pathologic findings in seven patients. RESULTS: In all patients, CT scans showed retraction of the capsular surface of the liver (15 diffuse, seven focal) with a lobular margin, a finding also seen in advanced cirrhosis. The retraction occurred at the site of subjacent metastases. Findings evolved over 1-3 months. Six of seven patients had pathologic findings suggestive of nodular regenerative hyperplasia. No patients had pathologic evidence of cirrhosis. CONCLUSION: In patients undergoing systemic chemotherapy for breast cancer metastatic to the liver, a pattern may develop that mimics the CT appearance of hepatic cirrhosis. Pathologic findings suggest nodular regenerative hyperplasia as a possible cause. PMID- 7992735 TI - Echoplanar MR imaging of the liver in patients with focal hepatic lesions: quantitative analysis of images made with various pulse sequences. AB - OBJECTIVE: We undertook this study to evaluate pulse-sequence performance in terms of liver signal-to-noise ratio (SNR) and lesion-liver contrast-to-noise ratio (CNR) on T1- and T2-weighted echoplanar MR imaging. SUBJECTS AND METHODS: Forty-nine patients referred for MR imaging of the liver were examined at 1.5 T with echoplanar MR imaging using spin-echo, inversion-recovery, and gradient-echo pulse sequences. T2-weighted spin-echo (TE = 25, 50, 100, and 150 msec), T1 weighted inversion-recovery (T1 = 100, 380, 600, and 800 msec), and T2*-weighted gradient-echo (TE = 20 msec) images were acquired after one excitation (TR = infinite), using a 128 x 128 data matrix. T2-weighted spin-echo (TE = 20, 50, 100, and 150 msec) images were also obtained with two excitations (TR = 6 sec), resulting in a 128 x 256 data matrix. Signal intensity measurements were made to calculate liver SNR and lesion-liver CNR. RESULTS: Single-excitation, T2 weighted, spin-echo images at a minimum TE of 25 msec provided the highest liver SNR (p < .05). Single-excitation, T2-weighted, spin-echo images at TEs of 50 and 100 msec, and T1-weighted inversion-recovery images at Tls of 100 and 380 msec provided the highest lesion-liver CNR (p < .05). However, the latter two pulse sequences had considerably inferior liver SNR (p < .05). CONCLUSION: Single excitation, T2-weighted, spin-echo images provide both superior liver SNR and superior lesion-liver CNR. These results can be used to guide technique selection when echoplanar MR imaging is used to examine the liver. PMID- 7992736 TI - Portal venous and segmental anatomy of the right hemiliver: observations based on three-dimensional spiral CT renderings. AB - OBJECTIVE: The purpose of this study was to evaluate the segmental anatomy of the right hemiliver and to assess whether the right hepatic vein and right portal trunk are accurate indicators of the position of the right and transverse scissurae, respectively. SUBJECTS AND METHODS: We examined 26 patients with spiral CT using 5-mm slices, reconstructed at 2-mm intervals. Three-dimensional renderings of the portal and hepatic venous structures were created. The portal ramification pattern and relationship between the hepatic veins and portal system were evaluated. RESULTS: In the right hemiliver, an anterosuperior sector and a posteroinferior sector were present in all patients. In addition, in nine patients, a total of 15 accessory portal sectors were present, each arising directly from the portal bifurcation or the right portal trunk. Further subdivision of the portal sectors showed marked individual variability, with no prevailing branching pattern. The scissura between the anterosuperior and posteroinferior sectors showed an angled orientation--its cranial part was tilted posteriorly (average, 58.4 degrees) and its caudal part was tilted anteriorly (average, 2.8 degrees)--relative to the coronal plane. In 24 patients, portal branches crossed the plane of the right hepatic vein. No transverse scissura could be seen in the anterosuperior or posteroinferior sector. CONCLUSION: The right hemiliver could be divided into anterosuperior and posteroinferior sectors in all patients studied. Many patients have accessory sectors. Further subdivision into portal segments can be described only after the individual portal branching pattern has been studied. The right hepatic vein is an inaccurate indicator of the position of the right scissura. No clear transverse scissura can be seen in the right hemiliver. PMID- 7992737 TI - Preoperative localization of hepatomas by sonography with microbubbles of carbon dioxide. PMID- 7992738 TI - Tumors of the adrenal gland: findings on CT and MR imaging. AB - Adrenal gland imaging has improved drastically since the advent of CT and MR imaging. The purpose of this essay is to illustrate findings on cross-sectional imaging of adrenal gland tumors. Emphasis is given to imaging features that help to characterize specific lesions. PMID- 7992739 TI - MR diagnosis of meniscal tears: analysis of causes of errors. AB - OBJECTIVE: MR imaging of the knee is an accurate method for diagnosing meniscal tears. However, MR findings do not always agree with surgical findings. In a retrospective study, we analyzed the various causes of incorrect MR diagnoses. MATERIALS AND METHODS: We reviewed a series of 400 MR examinations for suspected meniscal tears in which the diagnostic accuracy was 90%. In this group, we found 70 patients in whom the original MR diagnosis did not agree with the surgical findings. Three musculoskeletal radiologists independently reviewed each of the 70 MR examinations without knowledge of the original interpretation or the surgical findings. Their interpretations and the MR images then were correlated with the surgical findings. The original incorrect diagnoses were categorized as being due to unavoidable errors, errors in interpretation, or errors made because of equivocal MR findings of a tear. Unavoidable errors were defined as false positive and false-negative diagnoses that could not be avoided, even in retrospect. RESULTS: Of the 83 original diagnostic errors made in the MR evaluation of 800 menisci, 33 (40%) were unavoidable errors, 32 (39%) were due to equivocal MR findings, and 18 (21%) were due to interpretation errors. The unavoidable errors consisted of 21 missed meniscal tears and 12 false-positive MR diagnoses. In the false-positive cases, the menisci were interpreted as torn on MR images by all three observers, but no tear was found at arthroscopy. Subtle MR findings that were equivocal for a tear caused both false-positive and false negative diagnoses. Seven of the 18 interpretation errors occurred when normal variants were mistaken for a tear. CONCLUSION: Using conventional coronal and sagittal spin-echo MR imaging, we could not identify 21 (6%) of the 333 meniscal tears, even in retrospect. In addition, subtle findings that are equivocal for a tear may still make MR diagnosis of every torn meniscus difficult even for experienced radiologists. Unavoidable false-positive diagnoses due to healed tears or tears missed at arthroscopy are an infrequent problem occurring in only 1.5% of the original 800 menisci evaluated with MR imaging. PMID- 7992740 TI - MR diagnosis of superior labral anterior posterior (SLAP) injuries of the glenoid labrum: value of routine imaging without intraarticular injection of contrast material. AB - OBJECTIVE: Superior labral anterior posterior (SLAP) lesions are peculiar types of tears that involve the superior and anterior aspects of the glenoid labrum and extend posteriorly. The biceps tendon may also be involved in the injury. There have been conflicting reports in the literature about the value of MR imaging in depicting these injuries. Some authors have advocated imaging in special planes and, more recently, the use of intraarticular injection of contrast material to facilitate the diagnosis of SLAP injuries. Symptoms of SLAP injury of the glenoid labrum are nonspecific, and patients are often imaged according to routine imaging protocols that include images in axial, oblique coronal, and oblique sagittal planes using spin-echo pulse sequences. Intraarticular injection of contrast material is not part of routine MR imaging of the shoulder. We sought to determine the value of routine MR imaging without intraarticular contrast enhancement in the diagnosis of SLAP injuries of the glenoid labrum. MATERIALS AND METHODS: The MR images of eight patients with arthroscopically proved SLAP lesions were selected for this study. The MR imaging appearance of the glenoid labrum, biceps tendon attachment, and rotator cuff tendons were retrospectively evaluated in the axial, oblique coronal, and oblique sagittal planes in each case. The findings were correlated with the surgical observations. RESULTS: All eight patients showed an abnormal labrum on the coronal MR images, on 88% of the axial images, and on 50% of the sagittal images. An oblique or horizontal linear focus of increased signal was seen to traverse the labrum in 50% of the cases on sagittal images. Fifty percent of the cases also showed an intraarticular body, presumably representing the displaced fragment of a bucket-handle tear, on all imaging planes (the MR "Cheerio" sign). CONCLUSION: Routine MR imaging of the shoulder without intraarticular injection of contrast material is useful in the diagnosis of SLAP injuries of the glenoid labrum. PMID- 7992741 TI - Ulnar collateral ligament of the thumb: MR findings in cadavers, volunteers, and patients with ligamentous injury (gamekeeper's thumb). AB - OBJECTIVE: The ulnar collateral ligament bridges the ulnar aspect of the first metacarpal and the proximal phalanx and functions as a major stabilizer of the first metacarpophalangeal joint. Acute or chronic injury of this ligament is referred to as gamekeeper's thumb. The objectives of this study were to (1) determine the MR appearance of the ulnar collateral ligament of the thumb in cadavers and volunteers and (2) analyze the MR findings in patients with gamekeeper's thumb, especially with regard to the value of MR in detecting clinically significant displacement of the ligament (Stener lesion). MATERIALS AND METHODS: MR imaging of the first metacarpophalangeal joint was performed in three volunteers, two cadaveric specimens, and 11 patients with acute injury. In the patients, the mechanism of injury was an abrupt abductive force on the thumb resulting in rupture of the ulnar collateral ligament. The diagnosis was confirmed by surgery in five patients and by clinical follow-up in the remaining six. Cryomicrotome sectioning of the cadaveric tissue blocks was performed to correlate pathologic and MR findings. Images were interpreted by one radiologist. RESULTS: MR images showed rupture of the ulnar collateral ligament in all 11 patients. Prospectively, Stener lesions (n = 3) could be differentiated from non Stener lesions (n = 8) in eight of 11 patients. Retrospectively, the correct diagnosis could be made in all 11 patients once the importance of determining the position of the ulnar collateral ligament relative to the adductor aponeurosis was understood. CONCLUSION: MR imaging of the first metacarpophalangeal joint depicts the ulnar collateral ligament and adductor aponeurosis to good advantage. It can also accurately show tears of the ulnar collateral ligament and thus be used to differentiate a rupture without significant retraction from a Stener lesion. This information is important in determining whether surgical or conservative management is indicated. PMID- 7992742 TI - Dual energy X-ray absorptiometry of the calcaneus: comparison with other techniques to assess bone density and value in predicting risk of spine fracture. AB - OBJECTIVE: The calcaneus has been proposed as an alternative site for assessment of bone mineral density (BMD) in women with osteoporosis. The objectives of this study were to evaluate the clinical usefulness of dual-energy X-ray absorptiometry (DXA) of the calcaneus for predicting spinal fracture and to compare the predictive value of assessment of BMD by DXA of the calcaneus, quantitative CT or DXA of the lumbar spine, and DXA of the most distal part of the radius. SUBJECTS AND METHODS: The study group consisted of 399 healthy volunteer women (aged 19-81 years) and 27 women (aged 44-85 years) who had osteoporosis. They had DXA of the calcaneus, quantitative CT and DXA of the lumbar spine, and DXA of the most distal part of the radius. T-score analyses were used to compare decreases in BMD in postmenopausal women with decreases in premenopausal women, and to compare decreases in women with and without osteoporosis. RESULTS: T-score analysis of age-related changes in BMD in the control subjects showed that densities in the calcaneus, the lumbar spine, and the most distal part of the radius decrease significantly with age in postmenopausal women. In women with osteoporosis (n = 27), BMDs in the calcaneus (DXA, p < .0002), L1-L3 (quantitative CT, p < .0001), L1-L4 (DXA, p < .0005), and the most distal part of the radius (DXA, p < .005) were significantly lower than those in healthy control subjects (n = 77). T-score analysis indicated that in women with osteoporosis, DXA of the calcaneus showed BMD losses greater than those shown by DXA of L1-L4 and the most distal part of the radius and similar to those shown by quantitative CT of L1-L3. Receiver-operating characteristic (ROC) analysis showed that findings on DXA of the calcaneus were as good a predictor of the risk of spinal fracture as findings on DXA of the lumbar spine and not as good as findings on quantitative CT of the lumbar spine. CONCLUSION: The results suggest that DXA assessment of BMD in the calcaneus is not a useful adjunct to other measurements. However, it can be used to predict the risk of fracture when better measures, such as quantitative CT, are unavailable. PMID- 7992744 TI - Osseous sarcoidosis of the foot: detection by MR imaging. PMID- 7992743 TI - Low-dose CT of developmental dysplasia of the hip after reduction: diagnostic accuracy and dosimetry. PMID- 7992745 TI - Vascular contact with the fifth cranial nerve at the pons in patients with trigeminal neuralgia: detection with 3D FISP imaging. AB - OBJECTIVE: Vascular contact with the trigeminal nerve at the pons is known to cause trigeminal neuralgia; however, this finding also is present in some asymptomatic subjects. We evaluated the usefulness of high-resolution MR imaging and MR angiography of the posterior fossa to determine the presence or absence of vascular contact with the fifth cranial nerve at the pons in patients with trigeminal neuralgia and in control subjects. SUBJECTS AND METHODS: The trigeminal nerves in 40 symptomatic patients and 114 asymptomatic control subjects were examined for the presence or absence of vascular contact at the pons by using three dimension (3D) fast inflow with steady-state precession (FISP) imaging. Imaging parameters were 35/7/15 degrees (TR/TE/flip angle) with a slab thickness of 55 mm and 64 partitions. Contrast-enhanced imaging was done in 10 of 12 patients with normal findings on an unenhanced scan. Axial, coronal, sagittal, and maximum-intensity-projection images were reviewed by two observers who had no knowledge of the clinical details. The findings on MR images were prospectively compared with the surgical findings in 25 patients. RESULTS: On the unenhanced MR images, vascular contact with the trigeminal nerve at the pons was identified in 70% of 40 nerves in patients with trigeminal neuralgia and in a further 15% following injection of contrast medium. Contact between the nerve and two vessels at the pons was seen in 10% of cases, and deformity of the nerve was present in 30% of cases. In the control group, vascular contact with the nerve was identified in 8% of 114 nerves. Contact between the nerve and two vessels or deformity of the nerve was not identified in any control subject. The difference between the two groups was highly significant regarding the presence or absence of vascular contact with the nerve at the pons (p < 0.001, x2 test), distortion of the nerve (p < .001), and contact between the nerve and two vessels (p < .001). The imaging findings were in agreement with the surgical findings regarding the presence or absence of vascular contact with the nerve in all 25 patients who had surgery. Complete or partial pain relief was achieved following microvascular decompression in all patients who had surgery. CONCLUSION: Despite the fact that vascular contact with the trigeminal nerve at the pons is not specific for trigeminal neuralgia, high-definition unenhanced and enhanced 3D FISP imaging and MR angiography at the posterior fossa are useful in determining the presence or absence of vascular contact with or deformity of, the fifth cranial nerve in patients for whom surgery is planned for treatment of trigeminal neuralgia. PMID- 7992746 TI - MR measurements of the hippocampus for lateralization of temporal lobe epilepsy: value of measurements of the body vs the whole structure. AB - OBJECTIVE: Measurements of the volume of the hippocampus have been used preoperatively to determine the side of the hippocampus involved in patients with intractable temporal lobe epilepsy. However, the method used is time consuming and requires special training. The purpose of this study was to determine the validity of using measurements of the volume of the hippocampal body as a substitute for measurements of the volume of the whole hippocampus in patients with temporal lobe epilepsy. SUBJECTS AND METHODS: The study group consisted of 33 patients with intractable temporal lobe epilepsy due to presumed hippocampal sclerosis and 30 control subjects. Of the 33 patients with intractable temporal lobe epilepsy, 30 had hippocampal sclerosis and three had normal findings on pathologic examination of the hippocampus. T2-weighted fast spin-echo images were used to determine hippocampal volumes. Volumes were calculated by summing the sectional areas of the entire hippocampus and of the hippocampal body. Correlation between the volume of the hippocampal body and the volume of the whole hippocampus was determined. The sensitivity and specificity of measurement of the volume of the hippocampal body for lateralizing the foci responsible for seizures in patients with presumed hippocampal sclerosis were compared with those of measurement of the volume of the whole hippocampus. RESULTS: Significant linear relationships were noted between volumes of the hippocampal body and volumes of the whole hippocampus (p < .001). The sensitivity and specificity of measurements of volumes of the hippocampal body were identical to those of measurements of volumes of the whole hippocampus (87% and 100%, respectively). CONCLUSIONS: Our results show that segmental MR measurements of the body of the hippocampus are as accurate as measurements of the whole hippocampus for lateralizing temporal lobe epilepsy before surgery. Because segmental measurements are less time consuming and require less experience to perform, they are considered the procedure of choice. PMID- 7992747 TI - Diagnosis of recurrent brain tumor: value of 201Tl SPECT vs 18F fluorodeoxyglucose PET. AB - OBJECTIVE: This prospective study was designed to compare the sensitivity and specificity of a relatively simple examination, 201Tl chloride single-photon emission CT (SPECT), with a more complex examination, 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET), in patients thought to have recurrent brain tumor. Because both agents have been shown to be markers of viable tumor, we hypothesized that their sensitivity and specificity should be the same. SUBJECTS AND METHODS: Nineteen patients with evidence of recurrent tumor on CT or MR images were studied with both 201Tl SPECT and FDG PET imaging. Two patients were examined twice, so a total of 21 studies were evaluated. The 201Tl SPECT and FDG PET examinations were performed on the same day in 17 patients, and the remaining four examinations were done within 1 week of one another. Three reviewers independently interpreted each Tl SPECT and PET scan. Inappropriate regional increases in 201Tl or FDG activity were considered indicative of tumor recurrence. Sensitivity and specificity values were based on biopsy results and clinical follow-up. The final diagnosis was tumor recurrence in 16 cases and radiation necrosis in 5 cases. The relationship of scan results to survival was analyzed. RESULTS: The sensitivity and specificity of the 201Tl examination for detecting tumor recurrence were 11 (69%) of 16 and two (40%) of five, respectively; values for the FDG PET examination were 13 (81%) of 16 and 2 (40%) of 5, respectively. In patients with recurrent tumors less than 1.6 cm in size, results were false-negative in four 201Tl SPECT examinations and three FDG PET studies. All tumor lesions 1.6 cm or larger (n = 8) were detected. Agreement among the three nuclear medicine specialists was complete for each of the 201Tl SPECT scans. There was disagreement on the interpretation of five (24%) of the 21 FDG PET scans, which was resolved by consensus. Scintigraphic findings did not correlate with patients' survival times. CONCLUSION: We were unable to detect a statistically significant difference in sensitivity or specificity between the 201Tl SPECT and FDG PET scans. Both techniques were sensitive for tumor recurrence with lesions less than 1.6 cm or larger. However, given the greater availability, simplicity, and ease of interpretation and the lower cost of the 201Tl SPECT studies, this technique should be considered for detection of tumor recurrence with lesions that are demonstrated to be 1.6 cm or larger on CT or MR examinations. PMID- 7992748 TI - CT of the temporal bone: findings after mastoidectomy, ossicular reconstruction, and cochlear implantation. AB - Because of its superior visualization of bone detail, compared with that of MR imaging, CT commonly is used in patients who have had otomastoid or other forms of temporal bone surgery. The already complex anatomy of the temporal bone is distorted by the combination of surgical procedures and preexisting abnormalities, making proper identification of the postoperative imaging studies difficult. The purpose of this essay is to familiarize radiologists with the more common neurootologic surgical procedures and the expected postoperative findings in patients who have had this type of surgery. Special emphasis is placed on the indications for the procedure and the distinguishing features associated with each procedure. PMID- 7992749 TI - Otologic bioimplants: ex vivo assessment of ferromagnetism and artifacts at 1.5 T. PMID- 7992750 TI - Thyroglossal duct cysts: variability of sonographic findings. AB - OBJECTIVE: The purpose of this study was to describe the sonographic features of thyroglossal duct cysts, emphasizing the variable sonographic appearances, and determine if the presence of infection or inflammation influences the sonographic appearance. MATERIALS AND METHODS: We reviewed the sonograms in 12 children (2 months-16 years old) with pathologically proven thyroglossal duct cysts (TDCs). The cysts were evaluated for location, size, cystic versus solid features, echogenicity, and wall thickness. The sonographic features then were compared with the pathologic findings. RESULTS: Sonograms of the 12 lesions showed that nine were midline at or near hyoid bone; two were to the right of midline in the submandibular region; and one was located to the left of midline in the neck. Cysts were from 0.5 cm to 4 cm in diameter. Five lesions were anechoic with no perceptible wall thickness. Seven lesions were hypoechoic. Two of the seven were homogeneously hypoechoic with thin borders. The remaining five lesions were hypoechoic but heterogeneous (complex). One lesion was hypoechoic with small anechoic spaces. Four lesions were largely cystic with dense internal echoes and thick walls. The presence of thick walls and internal echoes did not correlate with the presence or absence of inflammation on pathologic examination. No lesions in our series were hyperechoic. CONCLUSION: Our results indicate that TDCs have a variable sonographic appearance. Anechoic, homogeneously hypoechoic, and heterogeneous (complex) lesions occur. We found no correlation between the pathologic findings of infection and inflammation and the sonographic appearance of TDCs. Awareness of the variable sonographic appearance of the TDC is helpful when a midline lesion is encountered in the neck. PMID- 7992752 TI - Sonographic detection of fetal anomalies of the aortic and pulmonary arteries: value of four-chamber view vs direct images. AB - Some investigators support the notion that the four-chamber view of the fetal heart is sufficient for the sonographic identification of most serious heart defects [1, 2]. We have found that the evaluation of the great vessels (aorta and pulmonary artery) is crucial for the detection of some of the most common heart defects, such as tetralogy of Fallot and transposition of the great arteries [3 5]. Although many abnormalities of the great vessels can be recognized indirectly by an abnormal four-chamber view, the detection of the ductus-dependent lesions often requires evaluation of the aorta and pulmonary artery outflow tracts [3-5]. This pictorial essay illustrates abnormalities of the great vessels and shows those likely to be identified with a four-chamber view as opposed to those that require direct images of the great vessels for detection. PMID- 7992751 TI - Ovarian torsion in prepubertal and pubertal girls: sonographic findings. AB - OBJECTIVE: The purpose of this study is to report the range of gray-scale and color Doppler findings of ovarian torsion in prepubertal and pubertal girls to determine whether there is a difference in appearance between the two age groups. MATERIALS AND METHODS: The study population consisted of 20 patients, 11 who were prepubertal (ages 2 days to 6 years) and nine who were pubertal (ages 12-16 years), who had gray-scale sonograms and surgical confirmation of ovarian torsion. Color Doppler studies were obtained in 14 of 20 patients. All sonograms were reviewed retrospectively by two radiologists with attention to location of the twisted ovary, internal characteristics, and evidence of color Doppler flow. The results were then compared in the prepubertal and pubertal groups. RESULTS: Sonographic findings of torsion in 11 prepubertal patients included complex mass with septations and debris (6/11), cystic mass (1/11), and solid mass with peripheral cysts (4/11). The masses were located in the right lower quadrant (5/11), left lower quadrant (3/11), right adnexa (2/11), and right inguinal canal (1/11). Eight of nine pubertal patients had solid masses, and one had a thick walled cystic mass. Torsion involved the right ovary in nine patients and the left in 11. Color patterns included central flow (3/14), peripheral flow (6/14), and absence of flow (5/14) and did not correlate with age or gray-scale findings. CONCLUSION: Sonographic findings of ovarian torsion vary with age. Neonates and young children have extrapelvic cystic or complex cystic masses, whereas pubertal girls have predominantly solid masses in an adnexal location. In both groups of patients, color Doppler signal can be documented in many twisted ovaries. PMID- 7992753 TI - Sonographic evaluation of fetal growth: growth rate variability as a function of the interval between examinations. AB - OBJECTIVE: Fetal growth rates determined on the basis of findings at two separate sonographic examinations can be used to detect growth abnormalities. This article determines the relationship between the length of the interval between examinations and the associated variability in measured fetal growth rates. MATERIALS AND METHODS: We analyzed 1479 fetal measurements of the biparietal diameter, average abdominal diameter, and femur length from 539 normal pregnancies. Mean growth rates were computed as functions of gestational age. The standard deviation of the growth rate was computed as a function of the interval between examinations. RESULTS: The standard deviation of fetal growth rates is relatively constant when the interval between examinations is 8-10 weeks or more, but increases substantially when the interval is fewer than 6 weeks. CONCLUSION: From a purely statistical point of view, the optimal interval for assessment of fetal growth rates is 8-10 weeks or more. Shorter intervals, however, usually are mandated by the clinical situation. Correction factors can be used to determine the standard deviations and associated confidence intervals for fetal growth measured over a period of fewer than 10 weeks. PMID- 7992754 TI - Making global telemedicine practical and affordable: demonstrations from the Middle East. AB - OBJECTIVE: The purpose of this study was to demonstrate the first use of voice grade telephone lines for the international transmission of both high-resolution digital images (radiology and pathology) and video in near real-time. MATERIALS AND METHODS: Eight live demonstrations were performed from the United Arab Emirates and the Kingdom of Saudi Arabia at the invitation of the respective ministries of health. Thirty radiologic studies (CT, MR, and radiographs) were digitized, compressed, and transmitted to Cambridge, MA, where they were interpreted on diagnostic workstations (1792 x 2252 display matrix) by a team of subspecialist radiologists. Near real-time image transmission was achieved by combining wavelet-based image compression (average compression ratio of 23:1) and multiplexing technology that used four phone lines simultaneously. During each demonstration, one pathology image was transmitted from Cambridge to the demonstration site, where it was interpreted by a visiting pathologist. Video conferencing was implemented with a 64-kilobits-per-sec leased line from the United Arab Emirates and with four multiplexed telephone lines from Saudi Arabia. RESULTS: For teleradiology and telepathology, transmission times ranged from 2-5 min per image. Image fidelity was judged to be of diagnostic quality in all transmitted cases. The video link to the United Arab Emirates was highly reliable. Bandwidth for videoconferencing from Saudi Arabia was marginal on four voice-grade telephone lines, resulting in some downtime (10-20%). Live consultations provided by subspecialists in Cambridge assisted in the management of patients at both venues. The system was well received by both the referring physicians in the Middle East and the participants in the United States. CONCLUSION: Image compression and multiplexing technologies enabled high resolution teleradiology and telepathology as well as real-time video consultations over international telephone lines. While telecommunications systems are advancing rapidly in many parts of the world, those areas most in need of telemedicine services are likely to be the last to upgrade their telecommunications infrastructures. This "proof of concept" article outlines a practical and affordable approach that makes telemedicine more accessible to underserved areas worldwide. PMID- 7992755 TI - Composing documents for radiologic education: value of a computer workstation integrated with a hand-held digitizer and a 600 DPI laser printer. PMID- 7992756 TI - Improving report turnaround time: an integrated method using data from a radiology information system. AB - OBJECTIVE: In the face of a changing health care system and increased competition, radiology departments need to become more efficient. One measurement of efficiency is promptness in producing a final report. Many large radiology centers have radiology information systems (RIS) that track work flow, collecting tremendous amounts of data. Most, however, lack an appropriate analytic mechanism. We have developed an integrated system that allows continual monitoring of radiology work flow and thus of opportunities to apply interventions. This system can form an important component of the quality management process in the radiology department. MATERIALS AND METHODS: In developing the system, we identified seven key steps in the work-flow process. When left to chance, these steps occur out of sequence and large delays occur. A scheme was devised to improve the sequencing of the work flow by using the data collected from the RIS, sorted by radiology division and patient type. Biweekly, the appropriate data file is transferred to each division for analysis, via the department's computer network. A one-step process follows, using desktop Macintosh computers and a custom program written in Microsoft Excel. Extracted data are quickly converted into a tailored division summary, and a report is automatically generated. RESULTS: The result summary format is uniform throughout the department, allowing ease of review at divisional and departmental meetings. Problems can be immediately localized to a specific step in the work-flow process. Automation of much of the system allows continual, near-real-time review of work flow. Using this approach, we have seen a sustained reduction of average report turnaround time. CONCLUSION: This system allows continual monitoring of work flow. It is largely automated and lends itself well to inclusion in the quality management program of any radiology department. PMID- 7992757 TI - A century of radiology at the University of Toronto. PMID- 7992759 TI - Smoking leads to small-airways disease and destruction of lung parenchyma. Does stopping smoking simply slow these processes or does repair ensue? Does pulmonary function improve after cessation of smoking? PMID- 7992758 TI - Should I get informed consent for every procedure and every contrast agent injection? PMID- 7992760 TI - How should I respond to clinicians who ask me about breast cancer screening for women 40-50 years of age? PMID- 7992761 TI - Are liver windows necessary in body CT? PMID- 7992762 TI - Is a single negative core biopsy, clearly obtained from a suspicious lesion in the cirrhotic liver, sufficient to exclude the diagnosis of hepatocellular carcinoma as the cause of the lesion? PMID- 7992764 TI - More on spiral vs helical CT. PMID- 7992765 TI - Pleural thickening caused by leukemic infiltration: pleural findings. PMID- 7992766 TI - Massive edema due to gastric cancer: another variety of diffuse low attenuation on CT scans. PMID- 7992763 TI - A second opinion on health care reform. PMID- 7992767 TI - CT of insulinoma. PMID- 7992768 TI - Spring ligament of the foot. PMID- 7992769 TI - The pinto plug. PMID- 7992770 TI - Synthetic color images for contrast-enhanced MR imaging. PMID- 7992771 TI - Telemedicine comes of age. PMID- 7992772 TI - Fatal Streptococcus pneumonia infection due to hyposplenism. PMID- 7992773 TI - Physician impairment: current concepts. PMID- 7992774 TI - International cooperation. PMID- 7992775 TI - Robarts School parents support total communication. PMID- 7992776 TI - Appendix: sign communication guidelines at the Robarts School, London, Ontario. PMID- 7992777 TI - Self-esteem, family climate, and communication patterns in relation to deafness. AB - The purpose of the study presented in this article was to determine the effect that family communication patterns have on the self-esteem of deaf children. Deaf students at a southern residential school, ranging in age from 13 to 19, were administered the Modified Self-Esteem Inventory (MSEI) and the Subject Communication Questionnaire. The subjects' parents answered 10 questions about their communication patterns with their deaf child. The parents were not deaf themselves. Analysis of the data revealed that there is a positive relationship between the family's communication method and the deaf child's self-esteem such that parents who use total communication (speech, fingerspelling, and sign) have children whose self-esteem scores are higher than those of children whose parents use an oral-only method of communication (speech). The parents who were best able to communicate by using sign language had children whose self-esteem scores were higher than those of children whose parents were less skilled in sign language. Also, a positive relationship was found between student self-esteem and reading level. PMID- 7992778 TI - The role of adaptability and communication in fostering cohesion in families with deaf adolescents. AB - The families of 325 adolescents enrolled in local public high schools throughout the United States were surveyed to assess the relationship between the communication modes used by families and family cohesion. Cohesion is defined here as the degree of emotional bonding among family members. In a path analysis, family cohesion was predicted by the mother's use of sign language. In turn, the child's degree of hearing loss and the child's mode of communication predicted the mother's use of sign language. Based on the use of the FACES (family adaptability and cohesion evaluation) inventory and a parent communication questionnaire, the authors conclude that mothers who sign tend to be more family oriented. PMID- 7992779 TI - Number processing in deaf college students. AB - Magnitude comparison, calculation verification, and short-term memory span experiments were conducted as a means of investigating number processing in deaf college students. The level of accuracy shown by the deaf students did not differ from that shown by their hearing peers. However, mean response times for the deaf students were greater than those of the hearing students for all experimental tasks. The authors question the importance of development, working memory, and sign communication as factors that may contribute to explanations of the experimental results. PMID- 7992780 TI - Effects of early manual instruction on the oral-language development of two deaf children. AB - The speech and language training provided to deaf children at our clinic is done by the Kanazawa Method, which consists of reception and expression training in sign communication and auditory/oral language, as well as written-language training. In our investigation, we analyzed the acquisition of passive and active vocabulary in sign and oral language. The subjects were two children congenitally deaf at the 105 dB level or greater. Recorded-language samples through the age of 54 months were analyzed. Acquisition of sign occurred more quickly than oral language acquisition. The children's production of active nouns, function words, and "wh-" question words in sign was equivalent to that of hearing peers, and later this proficiency transferred to oral language. These results suggest that early presentation of sign is effective in the acquisition of function words and interrogative sentences, both of which are especially challenging for the Deaf. PMID- 7992781 TI - A pilot study of SPINE test scores and measures of tongue deviancy in speakers with severe-to-profound hearing loss. AB - Two developments show promise in the assessment and remediation of defective speech production in persons with hearing loss. A perceptual speech intelligibility test, the SPINE (for Speech Intelligibility Evaluation), is a simple, clinician-administered instrument which is valid, reliable, and clinically efficient. In addition, the development of acoustic measures of tongue deviancy, computed from formant frequencies, makes possible a direct lateral visualization of tongue placement in relation to standard vowel placement. In this study, SPINE test scores of 28 persons with severe-to-profound hearing loss were correlated with two measures of tongue deviancy during production of the vowels /i/, /a/, and /u/. For both measures of tongue deviancy, correlations with the SPINE were significant for the three vowels combined and for the isolated vowel /i/. These findings suggest that clinicians may ultimately have two different but complementary means of assessing speech production in persons with hearing loss. PMID- 7992782 TI - A guide to the diagnosis of learning disabilities in deaf and hard-of-hearing children and adults. AB - This article provides a guide to psychological tests and test procedures recommended for diagnosing learning disabilities in deaf and hard-of-hearing youth and adults. Tests are evaluated relative to their usefulness with deaf and hard-of-hearing persons in school and rehabilitation settings. These data provide the basis for recommendation of a battery of tests for use by school, vocational, and general psychologists in evaluating deaf and hard-of-hearing youth and adults for learning disabilities. PMID- 7992783 TI - Performance of a group of deaf and hard-of-hearing students and a comparison group of hearing students on a series of problem-solving tasks. AB - The purpose of this study was to compare the performance of a group of school-age deaf and hard-of-hearing students and a matched group of hearing students on a series of problem-solving tasks. The results indicated that the hearing group performed better than the deaf and hard-of-hearing group. As they got older, both groups made incremental gains in problem-solving ability, and the gap between the deaf and hard-of-hearing group and the hearing group narrowed. Possible reasons for the results are discussed and suggestions for intervention and future research are presented. PMID- 7992784 TI - Deaf children reading fables: using ASL summaries to improve reading comprehension. AB - This study was a cooperative effort of two university-based reading educators and a reading teacher-librarian who is deaf. An intervention technique was designed based on studies emphasizing the importance of using American Sign Language (ASL) to build deaf children's background knowledge before they read materials that support the learning of English. The teacher used the ASL summary technique; that is, she signed a summary of a fable in ASL without giving the moral lesson before having the students read the fable in printed English. "Retelling scores" were computed for seven deaf elementary school students who read some fables with the ASL intervention and read other fables without the intervention. The students' responses in telling the moral lesson of each fable were also scored. The data showed that the ASL summary technique increased the quantity and quality of the retelling scores; it also improved deaf readers' comprehension of the moral lessons of the fables. A description of the ASL summary technique and a discussion of its implications for teachers are provided. PMID- 7992785 TI - Molecular medicine: oligonucleotides. PMID- 7992787 TI - Discriminatory pricing lawsuits could change future of community pharmacy. PMID- 7992786 TI - Avoiding medication mix-ups. PMID- 7992788 TI - One lawyer's view of discriminatory pricing. PMID- 7992789 TI - Selection and use of beta-blockers for patients with cardiovascular disease. PMID- 7992790 TI - Adapting to providing pharmaceutical care. PMID- 7992791 TI - Creating pharmacy's future. PMID- 7992792 TI - Pharmacist-physician link: keys to effective outcomes management. PMID- 7992793 TI - Risk management in pharmacy: preventing liability claims. PMID- 7992794 TI - Estimation of metabolic rate using qualitative job descriptors. AB - This project developed two methods to estimate metabolic rate that can be used easily and provide acceptable precision. The methods were developed from the measurement of oxygen consumption on 80 typical jobs in automotive manufacturing. The Ready-Reference Method uses three easily identified, dichotomous characteristics to classify the job into one of four levels of metabolic rate. The characteristics are based on motion of the hands, weights or forces, and walking; standard error of estimate was 68 kcal/hour. The Component Method has four terms that account for hand motion, walking/carrying, lifting, and pushing/pulling. Hand motions and lifting factors are characterized by three or four categories with a reference value to make the determination easier by using more qualitative data. Walking/carrying and pushing/pulling data are noted as typical distances traveled in one minute. The standard error of estimate for this method was 62 kcal/hour. In addition to a smaller standard error of estimate, the further advantage of the Component Method over the Ready-Reference Method is an ability to point toward the largest contributors to metabolic rate. PMID- 7992795 TI - Comparative physiological responses of exercising men and women to 5 ppm hydrogen sulfide exposure. AB - A study compared the effects of inhalation of 5 ppm hydrogen sulfide (50% of its occupational exposure limit) on the physiological and hematological responses of healthy men and women during exercise. Subjects were 13 men (mean +/- SD for age, height, and weight = 24.7 +/- 4.6 yr, 173 +/- 6.6 cm, 73.1 +/- 8.1 kg, respectively) and 12 women (mean +/- SD for age, height, and weight = 22.0 +/- 2.1 yr, 165 +/- 8.2 cm, 63.4 +/- 8.6 kg, respectively). Subjects completed two 30 minute exercise tests on a cycle ergometer at 50% of their predetermined maximal aerobic power while breathing medical air or 5 ppm H2S from a specially designed flow system. The results indicated that there were no significant differences between the two exposures for the metabolic (oxygen uptake, carbon dioxide production, respiratory exchange ratio), cardiovascular (heart rate, blood pressure, rate pressure product), arterial blood (oxygen and carbon dioxide tensions, pH), and perceptual (rating of perceived exertion) responses in either sex. None of the subjects reported any adverse health effects subsequent to the H2S exposure. These results suggest that healthy men and women can safely perform moderate intensity work in environments contaminated with 5 ppm H2S. PMID- 7992796 TI - An alternative method for the analysis of phenol and o-, m-, and p-cresol by capillary GC/FID. AB - An alternative method for the sampling and simultaneous analysis of phenol, o-, m , and p-cresol, employing XAD-7 as a sorbent for the collection of each analyte, is described. Desorption was achieved with methanol followed by analysis of all samples using gas chromatography with flame ionization detection. The separation of all analytes was achieved on a Stabilwax-DA capillary column. Sample collection and preparation was improved over current methods used at the National Institute for Occupational Safety and Health. The results obtained when a Stabilwax-DA capillary column was used in the analysis, as compared to those obtained using a Stabilwax capillary column, indicated achievement of baseline separation of the analytes. Peak resolution and overall peak shape were enhanced by the use of the Stabilwax-DA column. Lower limits of detection were achieved for each analyte. Desorption efficiency and storage stability results (30 days) were acceptable. Sample stability in solution and on solid sorbent tubes was examined. The relative standard deviation of the analytical portion of the method was found to be 0.045. This method provides a simplified, concise, simultaneous analysis of phenol, o-, m-, and p-cresol. PMID- 7992797 TI - Workers' exposure to airborne bacteria and endotoxins at industrial wastewater treatment plants. AB - A study of sewage workers' exposure to airborne culturable bacteria and inhaled endotoxins was performed at nine waste-water treatment plants that treat mainly industrial effluents. Airborne endotoxins were collected on glass fiber filters and analyzed using a chromogenic limulus assay. Endotoxin concentrations measured in the immediate vicinity of the waste-water treatment process varied from 0.1 to 350 ng/m3. The eight-hour time weighted average concentrations of endotoxin to which workers were exposed exceeded the suggested exposure limit (30 ng/m3 endotoxin) at four of the plants. Air samples of culturable bacteria concentrations varied between 10 and 10(5) colony-forming units/m3. Of the particles carrying culturable bacteria, 88% had an aerodynamic diameter of less than 4.7 microns. The most common genera of airborne gram-negative bacteria were acinetobacter, citrobacter, enterobacter, klebsiella, and pseudomonas. High levels of exposure to bacteria and bacterial endotoxin usually were related to certain phases of the treatment process. The microbiological contamination of air was highest near the inlets where incoming wastewater entered the basins, in the sludge treatment area, and inside the biofilter tower. In these spaces it is necessary to control and reduce exposure to airborne bacteria and endotoxin at wastewater plants. PMID- 7992798 TI - Bioaerosol sampling in field studies: can samples be express mailed? AB - Bioaerosol sampling for viable microorganisms was conducted in 25 dairy barns in summer and in winter to examine the relationship of sample storage and shipping in determining bioaerosol concentrations separately for yeasts, molds, mesophilic bacteria, and thermophilic organisms. The study also compared the performance of three sampling methods--(1) all-glass impinger (AGI) used with peptone solution in both seasons and (2) betaine solution in winter; and (3) the nuclepore filtration and elution (NFE) method, using air filtration with subsequent elution and culturing--which were studied in a pairwise fashion with duplicate, simultaneous, side-by-side sampling. For each sample, one duplicate was analyzed within two hours in a laboratory less than 50 km from the sampling site, while the other was express-mailed to the authors' laboratory. Concentrations of all microorganisms measured by the AGI peptone method were unaffected by mailing in winter, but mesophilic bacteria increased in summer. AGI betaine samples were unchanged except for increased concentrations of molds after mailing in winter. Yeasts and mesophilic bacteria significantly decreased after mailing of NFE samples. Pairwise comparison of the sampling methods in winter yielded no significant differences in airborne concentrations for the yeasts, mesophilic bacteria, and thermophilic bacteria. Both AGI betaine and NFE methods had significantly greater concentrations of molds than AGI peptone. In summer, concentrations of yeasts and mesophilic bacteria were significantly greater with AGI peptone, as were molds with the NFE method.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7992799 TI - The use of recovered memories outside of therapy. PMID- 7992800 TI - Suggestibility and repressed memories of abuse: a survey of psychotherapists' beliefs. AB - The mental health field is deeply divided in its views regarding the possibility of creating false memories of sexual abuse through suggestive procedures. Psychotherapists in clinical practice were surveyed regarding their views on memory and hypnosis in order to assess how their perspectives might influence their clinical methods. Survey data regarding hypnosis and suggestibility indicate that while psychotherapists largely view hypnosis favorably, they often do so on the basis of misinformation. A significant number of psychotherapists erroneously believe, for example, that memories obtained through hypnosis are more likely to be accurate than those simply recalled, and that hypnosis can be used to recover accurate memories even from as far back as birth. Such misinformed views can lead to misapplications of hypnosis when attempting to actively recover memories of presumably repressed episodes of abuse, possibly resulting in the recovery of suggested rather than actual memories. PMID- 7992801 TI - A case of the psychotherapist's fallacy: hypnotic regression to "previous lives". PMID- 7992802 TI - Truth in memory: ramifications for psychotherapy and hypnotherapy. AB - In this article we address a number of issues relevant to the practice of psychotherapy and hypnotherapy: How reliable is memory? How are therapists' and clients' beliefs and expectancies related to pseudomemory formation? Are certain clients particularly vulnerable to pseudomemory creation? Does hypnosis pose special hazards for pseudomemory reports? What are the variables or factors that mediate hypnotic pseudomemories? In addition to reviewing the literature on these topics, we intend to sensitize the clinician to the potential pitfalls of critical reliance on the patient's memories, as well as uncritically accepted clinical beliefs and practices. PMID- 7992803 TI - Hypnotizability enhancement: clinical implications of empirical findings. AB - While some conceptualize hypnotizability as a stable attribute of the individual, there is a growing body of literature that indicates hypnotizability may be characterized as a constellation of potentially modifiable attitudes and skills that are strongly influenced by contextual factors. In this article I briefly review representative studies from the hypnotizability-enhancement literature and highlight several controversial issues that have emerged. Although the empirical debate regarding hypnotizability and its enhancement will continue, this literature review has produced findings that are of value to hypnotherapists who wish to facilitate optimal hypnotic responding and positive outcomes with their patients. Several of these findings and their implications for the clinical application of hypnosis are discussed. PMID- 7992804 TI - The hidden observer, hypnotic dreams, and age regression: clinical implications. AB - This article summarizes data from three studies (Mare, Lynn, Kvaal, Segal, & Sivec, in press; Lynn, Mare, Kvaal, Segal, & Sivec, 1993) designed to extend research on the "hidden observer" to two phenomena of clinical relevance: hypnotic dreams and suggested age regression. Subjects received suggestions for a hypnotic dream or age regression and then received suggestions for a "hidden observer" (i.e., the subject possesses a part of the self that is aware of images and ideas that the conscious mind is unaware of) with respect to the dream or age regression experience. Hidden reports contained more personally relevant information than the target suggestions (i.e., dream, age regression). Subjectives were also less likely to recall hidden reports. The high rate of hidden-observer responding (> 80%) was also evident in nonhypnotized simulating and relaxed subjects, although they did not exhibit as much primary process thinking in their dream reports as hypnotized subjects. Case studies of a trauma client and a forensic client are used to illustrate the clinical potential of hidden-observer suggestions. PMID- 7992806 TI - The interface of research and clinical practice. PMID- 7992805 TI - Comment on Torem's "Hypnotherapeutic techniques in the treatment of hyperemesis gravidarum". PMID- 7992807 TI - Idiographic approaches to hypnosis research (or how therapeutic practice can inform science). AB - We argue that both nomothetic and idiographic research strategies can advance scientific knowledge of therapeutic hypnosis. In particular, practitioners can make idiographic contributions to the scientific literature in a manner that will be received positively by a growing number of behavioral scientists. Broad methodological issues and concerns specific to hypnosis research are discussed. PMID- 7992808 TI - Clinical hypnosis as a nondeceptive placebo: empirically derived techniques. AB - Many psychological problems are maintained, in part, by dysfunctional response expectancies, and changing those expectations is an essential part of treatment. Hypnotic inductions alter response expectancies and have been shown empirically to substantially enhance the effects of psychotherapy. Therefore, hypnosis can be used therapeutically as a nondeceptive placebo. Expectancy plays a major role in hypnotic inductions and their effects. Clinical procedures suggested by these data are explored. PMID- 7992809 TI - Experimental evidence of a plant meridian system: II. The effects of needle acupuncture on the temperature changes of soybean (Glycine max). AB - When stainless steel needles were inserted opposite each other in the stem near the unifoliolate buds of soybean plants and retained there for the whole experiment, leaf temperatures increased for two consecutive days. Following acupuncture, the mean temperature of the main vein in the first and second days increased 0.59 degree C and 0.48 degree C, respectively, while the temperature of mesophyll increased only 0.50 degree C and 0.47 degree C in the first and second days. These results are very consistent with studies on the human meridian system. This is our second report on experimental evidence that plants may have a meridian system as is known to exist in mammals. PMID- 7992810 TI - Absorption of subcutaneous injection of Tc-99m pertechnetate via acupuncture points and non-acupuncture points. AB - SC-RNV, a new method of radionuclide venography by subcutaneous injection of Tc 99m pertechnetate at acupuncture points K-3 (Taixi), was developed in our laboratory. To further investigate whether K-3 is the best point for SC-RNV, Tc 99m pertechnetate was subcutaneously injected at K-3 on one foot and at one of the 11 other acupuncture points (APs) or 3 nonacupuncture points (NAPs) on the opposite foot, simultaneously, in 157 subjects without evidence of venous disorder. The absorption of radioisotopes from each injection site was evaluated by analyzing the time-activity curve at a region of interest set upon over the lower leg above the injection site. The results revealed that the absorption of radioisotopes via K-3 (Taixi) was better than that via NAPs, evidenced by higher peak activity and greater absorption rate. However, there was no significant difference between K-3 injection and other APs injections except Liv-2 and Liv-3. These results indicate that absorption of radioisotopes via APs is better than via NAPs. This together with the fact that K-3 is easier to detect than other APs in feet, suggests that K-3 is a good point for SC-RNV. PMID- 7992811 TI - Effects of acupuncture and moxibustion on intestinal motility in mice. AB - To study the effects of acupuncture and moxibustion on intestinal motility, the distance of intra-intestinal movement of a carbon solution injected into the stomach of a mouse was evaluated. Intestinal motility was also evaluated using several drugs to accelerate or reduce intestinal motility. Our results indicate that intestinal peristalsis was accelerated significantly by acupuncture at the abdomen, but suppressed by moxibustion. The intestinal peristalsis acceleration by vagostigmin was reduced significantly by both acupuncture and moxibustion, while the reduction of intestinal peristalsis by atropine was accelerated significantly. However, no remarkable changes of intestinal peristalsis were observed with treatment by acupuncture and moxibustion after reduction by epinephrine. PMID- 7992812 TI - Further analysis of a pilot study for planning an extensive clinical trial in traditional medicine--with an example of acupuncture treatment for stroke. AB - Statistical methods for evaluating the effects of treatments and prognostic factors in clinical trials are discussed. Exploratory data analysis, nonparametric methods, regression modeling, and regression diagnostics of influential cases are applied to the analysis of a pilot 'randomized' controlled trial on the treatment of acute stroke with acupuncture. The utility of this analysis for modifying patient eligibility criteria, determining required sample size and utilizing stratified randomization in a future extensive stroke trial is discussed. PMID- 7992813 TI - Immunopharmacological studies of low molecular weight polysaccharide from Angelica sinensis. AB - A low molecular weight polysaccharide has been isolated from the rhizome of Angelica sinensis (Oliv.) Diels (Umbelliferaer). It has a molecular weight of approximately 3,000 and consists of protein (4.73%) and carbohydrate (85.85%) of which 5.2% is uronic acid. It shows strong anti-tumor activity on Ehrlich Ascites tumor bearing mice. It also exhibits immunostimulating activities, both in vitro and in vivo. PMID- 7992814 TI - Immunomodulatory effect of fu-fang-tai-pan-pian, a traditional Chinese tonic medicine. AB - The purpose of this study was to evaluate the effect of the traditional Chinese medicine Fu-Fang-Tai-Pan-Pian on responsiveness of mouse spleen leukocytes to the mitogens concanavalin A (con A), phytohemagglutinin (PHA), and bacterial endotoxin (LPS). Aqueous and chloroform/methanol extracts of the drug were prepared and added to mitogen-stimulated cultures at doses ranging from 0.625% to 20% by volume. The aqueous extract depressed responsiveness to all mitogens at all doses tested, and was significantly more potent in this regard than the organic extract. The organic extract depressed responsiveness at low dilutions; however it significantly stimulated responsiveness to PHA and LPS, but not to con A, at dilutions of 2.5% or less. The relative ability of compounds partitioning into aqueous and organic extracts of the medicinal mixture to both stimulate and depress the ability of lymphocytes to proliferate may provide insight into the mechanism of action of this and related medicines. PMID- 7992815 TI - Hepatoprotective effects of Taiwan folk medicine: wedelia chinensis on three hepatotoxin-induced hepatotoxicity. AB - The hepatoprotective effects of a Taiwanese crude herb, Hwang-hua-mih-tsay (Wedelia chinensis (Osbeck) Merr.), were investigated. Acute hepatitis was induced by three hepatotoxins: carbon tetrachloride and acetaminophen in mice, and D(+)-galactosamine in rats. After treatment with W. chinensis (300 mg/kg, p.o.) at 2, 6 and 10 hours, a reduction in the elevation of serum glutamate oxaloacetic transaminase (SGOT) and glutamate pyruvic transaminase (SGPT) levels was observed at 24 hrs after hepatotoxins were administered. These serological observations were confirmed by histopathological examinations. A microscopic examination of the liver showed a marked improvement in groups receiving W. chinensis. In order to further confirm the hepatoprotective effect of W. chinensis, all pharmacological and histopathological effects were compared with Bupleurum chinense DC. (family Umbelliferae), a well documented antihepatotoxicity herb. It was concluded that W. chinensis has a definite hepatoprotective effect against liver injuries. PMID- 7992816 TI - Antibacterial activity of alimentary plants against Staphylococcus aureus growth. AB - Alimentary plants were screened for antibacterial activity against a penicillin G resistant strain of Staphylococcus aureus. Twenty-five samples of plant material corresponding to 21 species from 13 families were used. Both aqueous and ethanol extracts were obtained from them. Antibacterial activity was determined by the agar-well diffusion method, using cephazolin as a standard antibiotic. Seventeen ethanol extracts were found active. Eugenia caryophyllata (clavo de olor*) flowers, Myristica fragans (nuez moscada*) seeds, Theobroma cacao (cacao*) seed bark, Triticum sp (trigo*) fruit, Zea mays (maiz*) fruit and Piper nigrum (pimienta*) ripe fruit produced some of the more active extracts (* = Argentine vulgar names). PMID- 7992817 TI - Anti-nociceptive effects of aconiti tuber and its alkaloids. AB - The anti-nociceptive effect of processed aconiti tuber (TJ-3021), one of the traditional oriental herbal medicines (Kampo), was investigated by utilizing various methods including repeated cold stress and adjuvant articular inflammation in rats and mice. Analgesic potency was compared with that of mesaconitine, a potent component of aconitine alkaloids, and other analgesic agents. It was found that mesaconitine was more potent than morphine, and a processed aconiti tuber [(TJ-3021), Tsumura-shuchi-bushi-matsu] showed some analgesic effect, although it was weaker than those of dichlofenac, aminopyrine and indomethacine. PMID- 7992818 TI - The effect of sho-saiko-to on concentration of vitamin E in serum and on granuloma formation in carrageenin cotton pellet-induced granuloma rats. AB - The effect of Sho-saiko-to on the concentration of vitamin E in serum and on the granuloma formation in Carrageenin cotton pellet-induced rats was investigated. As a result, in the granuloma rats of Sho-saiko-to group, a significantly improved inhibitory effect on granuloma formation and a higher concentration of vitamin E in serum, cholesterol and phospholipid were observed compared to the control group. Despite this lipid-increasing action by Sho-saiko-to, the concentration of serum lipid peroxide was significantly lower than in the control group. Furthermore, a significant negative correlation between the concentration of vitamin E and granuloma weight was observed. These results suggest that vitamin E plays an important role in promoting the anti-inflammatory effect of Sho-saiko-to. PMID- 7992819 TI - Acupuncture and blood studies in sickle-cell anemia. PMID- 7992820 TI - Inhibitory effects of sho-seiryu-to on acetylcholine-induced responses in nasal gland acinar cells. AB - Sho-seiryu-to, a traditional Japanese herbal medicine, has been used extensively in the treatment of allergic rhinitis. The effects of Sho-seiryu-to on electrical responses induced by acetylcholine in dissociated nasal gland acinar cells were investigated using patch-clamp and microfluorimetric imaging techniques. The application of Sho-seiryu-to inhibited both K+ and Cl- currents augmented by acetylcholine. The elevation of intracellular Ca2+ and Na+ concentrations induced by acetylcholine was also inhibited by Sho-seriyu-to. These findings suggest that Sho-seiryu-to attenuated the secretion of water and electrolytes from the nasal glands through an anti-cholinergic effect. PMID- 7992821 TI - Alteration of pulse in human subjects by three Chinese herbs. AB - Human subjects were fed with extract of three Chinese herbs, Panax ginseng, Panax quinquefolium roots and Ganoderma lucidum. Pulse of the radial artery was examined. Our results indicate that each herb has a specific effect on the Fourier components of the pulse, and is in agreement with traditional Chinese medical descriptions. PMID- 7992822 TI - Pharmacokinetics of the newer antidepressants: clinical relevance. AB - The newer antidepressants are a diverse group of compounds with distinct pharmacokinetic properties. The selective serotonin reuptake inhibitors (SSRIs)- paroxetine, sertraline, and fluvoxamine--have elimination half-lives of 15-26 hours. The extended half-life of fluoxetine (4-6 days) and its active metabolite, norfluoxetine (4-16 days), results in an extended time to steady-state and a prolonged washout period when dosing is discontinued. The SSRIs are administered as a single daily dose. Venlafaxine and nefazodone have short half-lives, 2-5 hours, and are dosed > or = 2 times daily. The newer antidepressants are all highly cleared from the body through hepatic metabolism. The biotransformation of all the drugs except paroxetine and fluvoxamine results in the formation of pharmacologically active metabolites. The newer antidepressants display a broad variability similar to the tricyclic antidepressants (TCAs) in steady-state drug concentrations. Due largely to a safer toxicity profile, the variability in clearance is of lesser importance with the newer antidepressants than with the TCAs. No useable concentration versus therapeutic effect relationship has been found with the newer drugs, and widely varying concentrations appear to have little relationship to adverse effects. Knowledge of kinetic characteristics is important for designing dosage regimens and avoiding potentially serious drug drug interactions that are mediated through inhibition of specific hepatic cytochrome P450 enzyme pathways. Each of the SSRIs inhibits at least one cytochrome P450 enzyme, and all of the SSRIs increase serum concentrations of concomitantly administered TCAs. PMID- 7992823 TI - Contemporary management of depression. AB - Major depression is a common and disabling disorder with far-reaching social and economic implications. Nonetheless, major depression is treatable by one of the many currently available antidepressants with response rates of approximately 65 70%. Treatment of depression has improved in recent years because of the availability of effective and well-tolerated antidepressants, such as the selective serotonin reuptake inhibitors (SSRIs). The currently available antidepressants are generally equally effective and are distinguished primarily by side-effect profiles. The side effects of tricyclic antidepressants (TCAs) are attributed to their nonspecific interaction with cholinergic, histaminergic, serotonergic, and dopaminergic receptors in the central nervous system. The secondary amine TCAs, nortriptyline and desipramine, are preferred among the TCAs because of a more favorable side-effect profile. The TCAs are cardiotoxic, and overdoses are frequently fatal. Adverse effects, including potentially fatal drug and food interactions, limit the use of the monoamine oxidase inhibitors (MAOIs); however, these agents have a role in the treatment of depression with comorbid anxiety, refractory depression, atypical depression, and bulimia. The SSRIs possess a class side-effect profile of headache, nausea, and sexual dysfunction. Individual differences in side effects may distinguish fluoxetine (nervousness, restlessness), sertraline (diarrhea, loose stools), and paroxetine (dry mouth). The SSRIs all inhibit certain cytochrome P450 isoenzymes involved in the metabolism of drugs, such as the TCAs, and each SSRI has been reported to increase plasma concentrations of concomitantly administered TCAs. Bupropion therapy is associated with a risk of seizure development, which can be minimized by multiple daily doses. Trazodone is sedating and can rarely cause priapism. The related compound, nefazodone, does not cause sexual dysfunction or priapism, but is associated with sedation. Venlafaxine, a recently available antidepressant that appears to have efficacy in treatment-refractory depression, may cause nausea that requires gradual upward dosage titration. Higher doses of venlafaxine may also cause elevations in blood pressure, heart rate, and serum cholesterol. As more is learned about the pathophysiology of depression, even more specific and well-tolerated antidepressants will be developed. PMID- 7992824 TI - Recent pharmacologic advances in antidepressant therapy. AB - The serotonergic properties of newer generation antidepressants underscore the role of 5-hydroxytryptamine (5-HT, serotonin) in both the pathophysiology and the pharmacotherapy of major depression. Clinical differences between selective serotonin reuptake inhibitors (SSRIs) and tricyclic antidepressants (TCAs) are attributed to the greater potency and selectivity for 5-HT transporter inhibition by the SSRIs and the comparatively weak interaction of the SSRIs with nonserotonin neurotransmitter receptors. The SSRIs, monoamine oxidase inhibitors (MAOIs), and TCAs share a common adaptive regulation of noradrenergic, 5-HT, and glutamate neurotransmission, suggesting possible unifying mechanisms of action underlying their antidepressant effects. In vivo neuroimaging techniques, such as positron emission tomography (PET) and single photon emission computed tomography (SPECT) have yielded a functional neuroanatomy of compromised neurocircuitry in major depression and promise to be invaluable in mapping the in vivo effects of future novel antidepressant drugs. PMID- 7992825 TI - Long-term management of depression. AB - Major depression is often a chronic and recurrent disorder. Findings from a landmark study, the Pittsburgh Study of Maintenance Therapies in Recurrent Depression, demonstrate that full doses of antidepressants prevent recurrent depression and that maintenance therapy lasting at least 5 years may be required for patients with severely recurrent disease. In addition, psychotherapy is a useful adjunct to antidepressant maintenance therapy in prolonging the duration between recurrent episodes. The currently accepted approach to preventing recurrent depression is to treat the acute episode to full remission and follow up by maintaining the patient on the full, acute dose used to achieve the initial response. The selective serotonin reuptake inhibitors (SSRIs) have been studied in recurrent depression and are rational choices for initial maintenance therapy because of demonstrated efficacy, safety, and tolerance during long-term therapy. PMID- 7992826 TI - Treatment of depression in late life. AB - Depression is a common, but treatable, source of suffering, excess disability, and caregiver strain in late life. It is important to take a long-term view of the treatment of late-life depression because of the high risk for relapse, recurrence, and chronic illness. Elderly patients with medical and neurological illness or bereavement-related depressions also merit greater attention. Recent data highlight several important caveats: (a) the role of medical and psychosocial factors in the course of major depression; (b) variability in etiology, clinical presentation, and treatment response; (c) need for additional studies of syndromal and subsyndromal depression in primary and long-term care facilities, particularly in patients > 75 years of age; and (d) importance of continuation and maintenance treatment to maintain quality of life and to lower the risk for chronic illness. Nortriptyline, desipramine, and the newer selective serotonin reuptake inhibitors (SSRIs), paroxetine and sertraline, are preferred pharmacotherapy for short-term and long-term treatment. The newer SSRIs should be further studied in controlled trials of elderly depressed patients, including those > 75 years and those with medical or neurological illness. Psychotherapy also appears to be of major importance in successful outcome but, as does pharmacotherapy, merits further controlled investigation in both short- and long term clinical trials. PMID- 7992827 TI - Cost-effectiveness considerations for managed care systems: treating depression in primary care. AB - This article addresses the management of depression in primary care from the perspective of a health maintenance organization. The rise of managed care systems is briefly discussed with reference to their impact on choice of treatment strategies. Cost-effectiveness considerations pertinent to a health maintenance organization are reviewed. A simplified protocol for the treatment of depression with paroxetine or imipramine in the primary care sector is presented and used as an example of cost calculations. Given the assumptions used in this cost-effectiveness model, it appears that the costs of treating depression in primary care with paroxetine are approximately equal to those found with the use of imipramine. Higher acquisition costs of paroxetine are balanced by the greater labor costs associated with imipramine. PMID- 7992828 TI - A pregnant possibility: crossing fetal tolerance with hematopoiesis. PMID- 7992829 TI - Comparative genomic hybridization: an overview. AB - Comparative genomic hybridization (CGH) is a newly described molecular cytogenetic assay that globally assays for chromosomal gains and losses in a genomic complement. In this assay, normal human metaphase chromosomes are competitively hybridized with two differentially labeled genomic DNAs (test and reference), which upon fluorescence microscopy, reveal the chromosomal locations of copy number changes in DNA sequences between the two complements. Application of CGH to DNAs extracted from fresh frozen specimens and cell lines of various tumor types has revealed a number of recurring chromosomal gains and losses that were undetected by traditional cytogenetic analysis. Few previously known sites were found to be in higher copy number, or lost by CGH, while many novel amplified regions were identified. These regions warrant further molecular genetic studies aimed at isolating the perturbed genes. Since CGH can also be performed on DNA extracted from formalin-fixed paraffin-embedded archived tumor specimens with few modifications, gains and losses of genetic material can be determined for specimens that would otherwise be unanalyzable. Prospective and retrospective application of CGH to tumor specimens would permit correlative studies to be performed, possibly identifying diagnostic and prognostic indicators of disease. CGH may also have a future role in detection and identification of chromosomal abnormalities in prenatal diagnosis and in dysmorphic anomalies. PMID- 7992830 TI - Alzheimer's disease and prion proteins: a meeting made in muscle. PMID- 7992831 TI - Development of central nervous system pathology in a murine transgenic model of human amyotrophic lateral sclerosis. AB - Transgenic mice expressing mutant Cu,Zn superoxide dismutase (SOD), containing a substitution of glycine at position 93 by alanine, develop disease prevalently affecting motor neurons. Light microscopical and ultrastructural studies reveal that the earliest pathological features are microvesiculation of large neurons of the anterior horns of the spinal cord. These vacuoles originate from dilation of rough endoplasmic reticulum and from degenerating mitochondria. At the end stage of the disease, the microvesicular pattern gives way to atrophic anterior horns showing severe neuronal depletion and hyaline, filamentous inclusions in some of the surviving neurons. Posterior horn neurons and dorsal root ganglia are not affected. With disease progression, moderate degeneration of anterior and lateral columns, severe degeneration of anterior roots, and mild degeneration in posterior columns and roots become apparent. This study shows that a mutation in SOD, known to occur in a percentage of familial amyotrophic lateral sclerosis patients, may affect only selective neuronal populations, although SOD is a ubiquitous enzyme. PMID- 7992832 TI - Abnormal accumulation of prion protein mRNA in muscle fibers of patients with sporadic inclusion-body myositis and hereditary inclusion-body myopathy. AB - Sporadic inclusion-body myositis is the most common progressive muscle disease of older patients. The muscle biopsy demonstrates mononuclear cell inflammation and vacuolated muscle fibers containing paired helical filaments and 6 to 10-nm fibrils, both resembling those of Alzheimer brain, and Congo-red positivity. Hereditary inclusion-body myopathy designates patients cytopathologically similar but without inflammation. In both muscle diseases, prion, and several proteins characteristic of Alzheimer brain--eg, beta-amyloid protein and hyperphosphorylated tau (which normally are expressed mainly in neurons), and apolipoprotein E--are abnormally accumulated in vacuolated muscle fibers, by unknown mechanisms. We now demonstrate in both muscle diseases that prion mRNA is strongly expressed in the vacuolated muscle fibers, which suggests that their accumulated prion protein results, at least partly, from increased gene expression. This, to our knowledge, is the first demonstration of abnormally increased prion mRNA in human disease. Another novel finding is the increased prion mRNA in human muscle macrophages, and both increased prion protein and prion mRNA in regenerating muscle fibers. The latter indicates that prion may play a role in human muscle development. PMID- 7992833 TI - Increased gelatinase A (MMP-2) and cathepsin B activity in invasive tumor regions of human colon cancer samples. AB - Gelatinase A (MMP-2) and cathepsin B are proteinases which have been proposed to participate in human tumor invasion and metastasis. Precise quantitation of the activity of these enzymes in invading tumors has not been previously described. We utilized a novel tissue microdissection technique to determine levels of enzyme activity in specific microscopic areas of invasive human colon cancer. Tissue specimens smaller than one high power field can be extracted from the samples and analyzed. Increased levels of pro-enzyme and active enzyme forms of gelatinase A (MMP-2) and increased cathepsin B activity were localized in regions of tumor invasion as compared with a matched number of normal epithelial cells from the same patient. Levels of progelatinase B (MMP-9) were also increased in the tumors; however, we did not observe activation of this enzyme. To investigate the mechanism of gelatinase A activation, we amplified DNA of specific microdissected tumor cell populations using polymerase chain reaction. We did not detect a mutation in the activation locus of the enzyme in any of the tumors studied, which suggests that activation may be due to up-regulation of a tumor associated gelatinase A activating species. Microdissection of frozen tissue sections may prove valuable in the study of proteinases in human tumor invasion as well as in the detection of genetic alterations in human cancers. PMID- 7992834 TI - Expression of p53 protein in precursor lesions and adenocarcinoma of human pancreas. AB - To evaluate the incidence and stage at which p53 alterations occur in human pancreatic carcinogenesis, we examined primary and metastatic carcinomas, carcinoma in situ, and hyperplastic lesions with and without atypia for p53 protein overexpression by immunohistochemical procedure. Overexpression of p53 was observed in 40% (10/25) of primary tumors, 29% (2/7) of metastatic tumors, 36% (5/14) of carcinoma in situ, and 35% (6/17) of hyperplastic lesions. These results suggest that p53 protein overexpression is not only a common genetic alteration but also occurs very early in the development of these tumors. It is suggested that p53 overexpression can be used as a marker to identify precursor lesions that have increased potential to develop into malignant tumors. PMID- 7992835 TI - Analysis of changes in DNA sequence copy number by comparative genomic hybridization in archival paraffin-embedded tumor samples. AB - Analysis of previously unknown genetic aberrations in solid tumors has become possible through the use of comparative genomic hybridization (CGH), which is based on competitive binding of tumor and control DNA to normal metaphase chromosomes. CGH allows detection of DNA sequence copy number changes (deletions, gains, and amplifications) on a genome-wide scale in a single hybridization. We describe here an improved CGH technique, which enables reliable detection of copy number changes in archival formalin-fixed paraffin-embedded tumor samples. The technique includes a modified DNA extraction protocol, which produces high molecular weight DNA which is necessary for high quality CGH. The DNA extraction includes a 3-day digestion with proteinase K, which remarkably improves the yield of high molecular weight DNA. Labeling of the test DNA with a directly fluorescein-conjugated nucleotide (instead of biotin labeling) improved significantly the quality of hybridization. Using the paraffin-block technique, we could analyze 70 to 90% of paraffin blocks, including very old samples as well as samples taken at autopsy. CGH from paraffin blocks was highly concordant (95%) with analyses done from matched freshly frozen tumor samples (n = 5 sample pairs; kappa coefficient = 0.83). The method described here has wide applicability in tumor pathology, allowing large retrospective prognostic studies of genetic aberrations as well as studies on genetic pathogenesis of solid tumors, inasmuch as premalignant lesions and primary and metastatic tumors can be analyzed by using archival paraffin-embedded samples. PMID- 7992836 TI - Fluorescent in situ hybridization in routinely processed bone marrow aspirate clot and core biopsy sections. AB - Fluorescent in situ hybridization (FISH) is a technique which complements conventional cytogenetic banding analysis by allowing the evaluation of cells in interphase as well as metaphase. This technique has been used to study air-dried peripheral blood and bone marrow aspirate smears. We have applied the FISH technique to study routinely processed sections of bone marrow aspirate clot and decalcified core biopsy specimens, fixed in either formalin or B5 and embedded in paraffin. We evaluated 28 specimens (8 aspirate clot and 20 core biopsy sections) for chromosome 8 copy number, studied previously by conventional cytogenetics, and found the following distribution: 15 with disomy, 11 with trisomy, and 2 with tetrasomy. Using a chromosome 8 alpha-satellite probe, we detected fluorescent hybridization signals in 18 of 28 specimens (64%); 6 of 8 (75%) aspirate clot sections, and 12 of 20 (60%) core biopsy sections. Ten of 13 (77%) B5-fixed and 8 of 15 (53%) formalin-fixed specimens had hybridizing signals. Specimen age was a significant factor; 10 of 11 (91%) specimens processed within the last 6 months showed signals, in contrast with 8 of 17 (47%) specimens older than 6 months. In the positive specimens, 200 cells were analyzed in areas where individual cells could be identified. In the disomic specimens, two signals per cell were seen in 34 to 66% of the cells. Rare cells (0-2%) with three signals were detected. In the trisomic specimens, three signals per cell were seen in 19 to 46% of the cells. In the tetrasomic specimens, four signals per cell were seen in 15 to 25% of the cells. We conclude that the FISH technique may be useful in the detection of numerical chromosomal abnormalities such as trisomy and tetrasomy 8 in routinely processed bone marrow aspirate clot and decalcified core biopsy sections. PMID- 7992837 TI - In situ characterization of antigenic and functional tissue factor expression in human tumors utilizing monoclonal antibodies and recombinant factor VIIa as probes. AB - Tissue factor (TF), the primary initiator of blood coagulation in vivo, is expressed in vitro by a variety of cells. Previous efforts to localize TF in tissue and cells have been limited principally to the use of immunological techniques. In the present study, we describe a novel functional probe for TF expression, which can be utilized to localize functional TF in situ in human cells and tissues. This probe, a biotinylated phe-pro-arg-chloro-methyl-ketone labeled rVIIa (FPR-ck-VIIa), interacts with TF via high-affinity binding sites. The binding of FPR-ck-VIIa, therefore, can be correlated with the ability of TF to activate clotting. In the described studies, TF antigen (TF:Ag) expression was examined immunohistochemically with various TF-specific monoclonal antibodies (MAbs) and was correlated with functional TF expression using our novel TF binding probe (eg, FPR-ck-VIIa). Initial results indicate that TF:Ag expression correlates with the expression of functional TF (TF:VIIa), and the specificity of both types of probes was confirmed. Parallel antigenic and functional TF expression in situ was demonstrated in various human tumors. We believe this to be the first demonstration of functional TF in situ in human cells and tissues. We suggest that FPR-ck-VIIa should prove a useful reagent for studying the role of TF in the pathogenesis of clotting complications of human disease. PMID- 7992838 TI - Immunohistochemical determination of in vivo distribution of Bax, a dominant inhibitor of Bcl-2. AB - The protein encoded by the bcl-2 gene is a regulator of programmed cell death and apoptosis. The cell survival-promoting activity of this protein is opposed by Bax, a homologous protein that forms heterodimers with Bcl-2 and accelerates rates of cell death. In this report, the in vivo patterns of bax gene expression were immunohistochemically assessed in the mouse, with a polyclonal antibody raised against a synthetic peptide corresponding to a unique region in the murine Bax protein. Direct comparisons were made with Bcl-2 by using anti-peptide antisera specific for the mouse Bcl-2 protein. The expression of bax was more widespread than bcl-2. For example, Bax immunoreactivity was present in the hepatocytes of the liver, the exocrine pancreas, and the renal tubule epithelial cells whereas Bcl-2 was absent from these tissues. Both the Bax and Bcl-2 proteins were present in several epithelia examined, including the small intestines, colon, breast, prostate, respiratory tract, and skin. The most intense Bax immunostaining was seen in cells located in the base of the crypts of the small intestinal mucosa, consistent with reports of high rates of spontaneous and inducible apoptosis in this region. Bcl-2 immunostaining was completely absent from these cells but was present in the absorptive epithelial cells of the small intestine. In contrast, Bax immunostaining in the colon tended to be stronger in the surface epithelial cells that had advanced up the crypts towards the lumen and that are destined for programmed cell death, whereas Bcl-2 immunoreactivity generally was stronger in the base of the colonic crypts. Similarly, bax expression in the gastric pits of the stomach occurred in a gradient such that higher levels of Bax immunostaining were found in the upper layers of gastric glands than in the lower regions. In addition, strong Bax immunostaining was detected in the androgen-dependent secretory epithelial cells of the prostate, whereas Bcl-2 was limited to the androgen-independent basal cells. Like Bcl-2, Bax was found in the thymic medulla but not the cortex, despite the propensity for immature cortical thymocytes to undergo apoptosis. Unlike Bcl-2, however, Bax immunostaining tended to be more intense in the germinal center lymphocytes of lymph nodes than in the interfollicular lymphocytes, consistent with the high rate of apoptotic cell death in the former.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 7992839 TI - Medullary carcinoma is associated with expression of intercellular adhesion molecule-1. Implication to its morphology and its clinical behavior. AB - The histological hallmarks for the diagnosis of medullary breast cancer are circumscription, syncytial architecture, diffuse inflammatory infiltrate, and highly atypical nuclei. The biological and prognostic implication is a lower propensity to metastasize. We studied 19 medullary carcinomas for expression of the intercellular adhesion molecule-1 and lymphocyte-function-associated antigen 1, Neu differentiation factor, tumor necrosis factor-alpha, and the expression of HER-2/neu, HER-4, and HER-3 receptors. Our study revealed that all of the 19 medullary carcinomas expressed the intercellular adhesion molecule-1 and lymphocyte function associated antigen. Eighteen of 19 cancers expressed Neu differentiation factor and tumor necrosis factor-alpha. All medullary cancers expressed the HER-2/neu receptor, however, in the majority of the cases, the staining was confined to the cytoplasm. Only 4 of 12 cancers expressed HER-4 and none of the eight medullary cancers tested expressed HER-3. By comparison, in a control group of infiltrating ductal carcinomas, expression of intercellular adhesion molecule-1, lymphocyte function associated antigen-1, and Neu differentiation factor was positive in about 25 to 30% of the cases, HER-4 was expressed in 75% and HER-3 in 95% of the cases. Taken together, our observations suggest that the expression of intercellular adhesion molecule-1, lymphocyte function associated antigen, Neu differentiation factor, and tumor necrosis factor-alpha as factors that may affect the special morphology and the biological behavior that characterizes medullary carcinomas. PMID- 7992841 TI - Bovine ENA, a new monocyte-macrophage derived cytokine of the interleukin-8 family. Structure, function, and expression in acute pulmonary inflammation. AB - A novel bovine neutrophil-activating peptide, bovine ENA (boENA), was identified in the conditioned media of endotoxin-stimulated bovine monocytes and alveolar macrophages. The chemotactic peptide was purified to homogeneity from conditioned media by cation-exchange chromatography and several steps of reversed-phase high performance liquid chromatography. The partial amino acid sequence of boENA was: VVRELRCVCLTTTPGIHPKTVSDLQVIAAGPVCSKVEVIATLKNGXXV. Its cysteine molecules are positioned identically to those of the C-X-C family of human proinflammatory peptides. BoENA shows structural (73% identity in amino acid sequence) and functional homology to human ENA-78, a product of the human type II epithelial cell line A549, as demonstrated in assays for chemotaxis, aggregation, shape change, and a rise in intracellular free calcium. The immunohistochemical identification of boENA in the hyperplastic type II alveolar epithelial cells and in pulmonary alveolar leukocytes of pneumonic bovine lungs strongly supports a role for ENA-78 in the genesis of pulmonary inflammation. PMID- 7992842 TI - Developmental and tissue-specific expression of prosaposin mRNA in murine tissues. AB - Prosaposin is a multifunctional locus in humans and mice that encodes in tandem and in the same reading frame four glycoprotein activators, or saposins, of lysosomal hydrolases. These ubiquitously expressed glycoproteins and the precursor, prosaposin, have been proposed to function in glycosphingolipid catabolic pathways and glycolipid transport. To characterize the temporal and spatial expression of the prosaposin locus, prenatal and postnatal mouse tissues were screened by in situ hybridization with a mouse antisense riboprobe for prosaposin. Prenatally, prosaposin mRNA was expressed differentially in the placenta and prominently in the decidua basalis and capsularis where expression was gestational age dependent. No other region of high-level expression was detectable in the prenatal mouse. In comparison, high-level differential expression of prosaposin was clearly evident postnatally in a variety of organs, including secretory epithelial cells of the choroid plexus, ependymal lining, upper trachea, esophagus, cortical tubules of the kidney, sertoli cells of the testes and epididymis. Discrete localization of prosaposin mRNA expression was also found in neurons of the cerebral cortex, cerebellar cortex, and lateral columns of the spinal cord as well as in hepatocytes of the mature liver. Very high levels of expression were found in specialized tissues including the Harderian glands and macrophages of lymph nodes, lungs, splenic tissue, and thymus. These studies indicate that the expression of the prosaposin locus, a presumed "housekeeping" gene, is under tissue- and cell-specific differential control. The spatial organization of expression suggests a role for this locus in the expression of glycosphingolipid-storage diseases. PMID- 7992840 TI - Synaptic pathology and glial responses to neuronal injury precede the formation of senile plaques and amyloid deposits in the aging cerebral cortex. AB - The cerebral cortices of macaques (ranging in age from 10 to 37 years; n = 17) were analyzed by immunocytochemistry and electron microscopy to determine the cellular and subcellular localizations of the amyloid precursor protein and beta amyloid protein, the cellular participants in the formation of senile plaques and parenchymal deposits of the beta-amyloid protein, and the temporal/spatial development of these lesions. Amyloid precursor protein was enriched within the cytoplasm of pyramidal and nonpyramidal neuronal cell bodies in young and old monkeys. In the neuropil, amyloid precursor protein was most abundant within dendrites and dendritic spines; few axons, axonal terminals, and resting astrocytes and microglia contained the amyloid precursor protein. At synapses, amyloid precursor protein was found predominantly within postsynaptic elements and was enriched at postsynaptic densities of asymmetrical synapses. The earliest morphological change related to senile plaque formation was an age-related abnormality in the cortical neuropil characterized by the formation of dense bodies within presynaptic terminals and dendrites and an augmented localization of the amyloid precursor protein to astrocytes and microglia. In most monkeys > 26 years of age, the neocortical parenchyma exhibited neuritic pathology and plaques characterized by swollen cytoplasmic processes, interspersed somata of neurons, and reactive glia within or at the periphery of senile plaques. Neurites and reactive astrocytes and microglia within these plaques were enriched with the amyloid precursor protein. In diffuse plaques, nonfibrillar beta-amyloid protein immunoreactivity was visualized within cytoplasmic lysosomes of neuronal perikarya and dendrites and the cell bodies and processes of activated astrocytes and microglia. In mature plaques, beta-amyloid protein immunoreactivity was associated with extracellular fibrils within the parenchyma; some cytoplasmic membranes of degenerating dendrites and somata as well as processes of activated glia showed diffuse intracellular beta-amyloid protein immunoreactivity. We conclude that morphological abnormalities at synapses (including changes in both pre- and postsynaptic elements) precede the accumulation of the amyloid precursor protein within neurites and activated astrocytes and microglia as well as the deposition of extracellular fibrillar beta-amyloid protein; neuronal perikarya/dendrites and reactive glia containing the amyloid precursor protein are primary sources of the beta-amyloid protein within senile plaques; and nonfibrillar beta-amyloid protein exists intracellularly within neurons and nonneuronal cells prior to the appearance of extracellular deposits of the beta amyloid protein and the formation of beta-pleated fibrils.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 7992843 TI - Tissue repair processes in healing chronic pressure ulcers treated with recombinant platelet-derived growth factor BB. AB - Cellular and molecular mechanisms responsible for the observed vulnerary effects of recombinant human platelet-derived growth factor BB (rP-DGF-BB) in man have not been elucidated. In a double-blinded trial, patients having chronic pressure ulcers were treated topically with either rPDGF-BB or placebo for 28 days. To explore how rPDGF-BB may induce chronic wounds to heal, biopsies were taken from the ulcers of a cohort of 20 patients from the trial and evaluated in a blinded fashion by light microscopy for 1), fibroblast content, 2) neovessel formation, and 3), collagen deposition. Electron microscopy also was used to assess fibroblast activation and collagen deposition. Before initiation of therapy most wounds had few fibroblasts and most of those present were not activated. When mean scores for the total active treatment phase (days 8, 15, and 29) for rPDGF BB-treated ulcers were compared with the scores for placebo-treated ulcers, fibroblast content was significantly higher for the rPDGF-BB-treated ulcers (P = 0.03, Kruskal-Wallis test). More significant differences in fibroblast and neovessel content were observed when six nonhealing wounds were eliminated from the analysis (three placebo, three treatment). Thus, in all healing wounds, rPDGF BB therapy significantly increased fibroblast (P = 0.0007) and neovessel (P = 0.02) content. These results were correlated with increased collagen fibrillogenesis by fibroblasts from healing rPDGF-BB-treated wounds, as assessed by intracellular procollagen type I immunostaining, and by electron microscopy, and were concordant with clinical measurements (eg, area of ulcer opening and ulcer volume) which showed greater healing in rPDGF-BB-treated wounds. These results suggest induction of fibroblast proliferation and differentiation is one mechanism by which rPDGF-BB can accelerate wound healing and that rPDGF-BB can augment healing responses within a majority of, but not all, nonhealing chronic pressure ulcers in man. PMID- 7992844 TI - Persistence, re-expression, and induction of pulmonary arterial fibronectin, tropoelastin, and type I procollagen mRNA expression in neonatal hypoxic pulmonary hypertension. AB - Changes in the structure and function of muscular pulmonary arteries are crucial for normal adaptation to extrauterine life and rapid changes in matrix protein gene expression are likely necessary for this adaptation. We hypothesized that pathological stimuli imposed at the time of birth would alter developmental changes in matrix protein gene expression thereby affecting the normal post uterine changes in pulmonary hemodynamics. We used in situ hybridization to examine the normal developmental expression of three extracellular matrix protein mRNAs, fibronectin, tropoelastin, and alpha 1 (I) procollagen, in muscular pulmonary arteries of both fetal and neonatal calves and assessed the impact of severe hypoxia-induced pulmonary hypertension on their expression. Morphometric techniques were used to assess whether changes in matrix protein mRNA levels were related to changes in matrix fiber accumulation. Exposure to chronic hypoxia postnatally resulted in the persistence, reexpression, and induction of fibronectin, tropoelastin, and alpha 1 (I) procollagen mRNAs, respectively, in muscular pulmonary arteries. In each case the hybridization signal was localized primarily to the adventitial layer of the vessel. Morphometric analysis showed that the increased hybridization signals seen correlated with an increase in both vascular elastin and collagen fiber volumes in the adventitial layer. We conclude that the change in expression of matrix genes in the pulmonary artery wall during exposure to chronic hypoxia is an important adaptive response to changes in hemodynamic factors and/or oxygen tension. The unchecked increase in matrix protein expression seen likely contributes to the pathological pulmonary arterial structural remodeling and loss of vasoreactivity that occurs during the development of severe neonatal pulmonary hypertension. PMID- 7992845 TI - Hepatic microcirculatory perfusion failure is a determinant of liver dysfunction in warm ischemia-reperfusion. AB - Hepatic ischemia-reperfusion (I/R) is characterized by circulatory and metabolic derangements, liver dysfunction, and tissue damage. However, little is known about the causative role of I/R-induced microcirculatory disturbance on the manifestation of postischemic reperfusion injury. Therefore, the intention of the study was to assess changes of hepatic microvascular perfusion (intravital fluorescence microscopy) as related to hepatic morphology (light/electron microscopy), hepatocellular integrity (serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) activities), and excretory function (bile flow). Sprague-Dawley rats were subjected to 20 minutes (group B, n = 9) and 60 minutes (group C, n = 9) of left hepatic lobar ischemia followed by 60 minutes of reperfusion. Sham-operated animals without ischemia served as controls (group A, n = 10). Lobar ischemia for 20 minutes followed by reperfusion resulted in a significant reduction of sinusoidal perfusion rate (93.9 +/- 1.4%; P < 0.05) and a decrease in erythrocyte flux (90.0 +/- 5.6%) when compared with controls (99.4 +/- 0.2 and 97.9 +/- 2.7%). This was accompanied by a significant increase of serum AST and ALT activities (P < 0.05) and a reduction of bile flow (P < 0.05). Prolongation of lobar ischemia (group C, 60 minutes) aggravated postischemic reperfusion injury (sinusoidal perfusion rate: 87.4 +/- 2.9%; erythrocyte flux: 62.1 +/- 8.4%) and was paralleled by severed hepatocellular damage. Electron microscopy of postischemic tissue demonstrated alteration of nonparenchymal cells (swelling of sinusoidal lining cells and widening of Disse's space) and substantial parenchymal cell damage (swelling of mitochondria, disarrangement of rough endoplasmatic reticulum, vacuolization, complete cytoplasmic degeneration). Initial postischemic increase in serum AST and ALT activities and reduction of bile flow directly correlated with the extent of microcirculatory failure (P < 0.01), ie, impairment of sinusoidal perfusion and decrease of erythrocyte flux, indicating the decisive role of microvascular perfusion failure for the manifestation of hepatic tissue damage and liver dysfunction. PMID- 7992846 TI - Isolation, propagation, and characterization of rat liver serosal mesothelial cells. AB - Although rat liver epithelial cell (RLEC) lines have been developed by a number of laboratories, the identity of the clonogenic nonparenchymal progenitors is unknown. To provide insight into the derivation of RLEC, we immunoisolated serosal liver mesothelial cells (LMC) and bile duct epithelial cells and attempted to propagate each epithelial cell population using culture conditions routinely employed to establish RLEC lines. Briefly, the selective reactivity of LMC with two bile duct cell surface markers, OC.2 and BD.2, was exploited to develop an immunocytochemical technique to isolate LMC. Livers were collagenase dissociated, the mesothelial capsule was "peeled" and digested with pronase to destroy contaminating hepatocytes, and rare biliary ductal epithelial cells were immunodepleted using OC.2. LMC were subsequently isolated by selective binding to magnetic beads adsorbed with BD.2 and cultured in supplemented Waymouths 752/1 media containing 10% fetal calf serum. Proliferating BD.2+ LMC rapidly formed epithelial-like monolayers that could be continuously subcultured after trypsinization. In contrast, attempts to establish cell lines from purified OC.2+ bile duct epithelial cells were unsuccessful. Results from reverse transcriptase polymerase chain reaction analysis confirmed that LMC expressed Wilms' tumor transcripts, a lineage marker for mesodermally-derived cells. In summary, our findings clearly demonstrate that LMC can be continuously propagated using culture conditions routinely employed to establish RLEC lines, an observation that supports the contention that some RLEC lines may be derived from LMC. PMID- 7992847 TI - Patterns of p53 mutations in squamous cell carcinoma of the lung. Acquisition at a relatively early age. AB - Squamous cell carcinoma (SQCC) of the lung is thought to arise after the accumulation of multiple mutations, including p53. To better characterize when p53 mutations are acquired, 37 SQCC of the lung were examined by polymerase chain reaction and single-strand conformation polymorphism analysis. Somatic p53 mutations were detected in nine tumors (24.3%). There were no significant differences in the stage, sex, or race between patients with or without p53 mutations. However, the patients with SQCC and p53 mutations were significantly (P = 0.0006) younger (mean age, 54.3 years) compared with patients without p53 mutations (mean age, 65). The topographical tissue distributions of the p53 mutations were examined by selective ultraviolet radiation fractionation. In all nine cases, the specific p53 mutant alleles were homogeneously present throughout the primary tumors, in all three examples with in situ carcinoma, and in all four cases with metastases. In one case, squamous metaplasia contiguous with the primary tumor also contained the same p53 mutation. Normal or hyperplastic and metaplastic or dysplastic epithelium not contiguous with the primary tumors lacked the specific p53 mutations. These findings suggest that p53 mutations are commonly acquired at a relatively early age, before the bulk of clonal expansion, and usually persist throughout the progression of SQCC of the lung. PMID- 7992848 TI - Macrophages express osteopontin during repair of myocardial necrosis. AB - Osteopontin is a secreted glycoprotein implicated in a variety of functions, including cell adhesion and migration. Because these functions may be of general importance in the response of tissue to injury, we examined osteopontin expression after experimental cardiac injury and human myocardial infarction. Rat hearts were injured by transdiaphragmatic freeze-thaw and examined from 1 to 28 days after injury. Osteopontin was absent from normal myocardium by immunocytochemistry, Western blotting, and in situ hybridization. On days 1 and 2 after injury, osteopontin mRNA and protein were expressed at high levels by macrophages infiltrating necrotic myocardium. Double labeling with the macrophage marker ED1, however, demonstrated that only a subset of macrophages expressed osteopontin. Western blot analysis showed a single 66-kd band in injured myocardium that was absent from control tissue. Although macrophages remained abundant in the ensuing granulation response and scar tissue formation, the expression of osteopontin was diminished on day 4 and markedly downregulated at 1 and 4 weeks after injury, with only rare cells expressing the message or protein. In a human heart with an 8-day-old myocardial infarct, there was abundant expression of osteopontin mRNA and protein in macrophages within the necrotic and granulation tissue. Transient expression of osteopontin was also observed in a subset of macrophages infiltrating lung, skin, and skeletal muscle injured during the experiment, indicating the response was not limited to the heart. Thus, synthesis of osteopontin by macrophages appears to be a generalized response in the reaction to tissue injury. Although macrophages persist in these lesions, osteopontin is dramatically downregulated as healing proceeds. These results provide the first evidence that osteopontin may be important in healing after tissue injury, possibly in cellular adhesion, chemotaxis, and/or phagocytosis. PMID- 7992849 TI - Macrophage activation and muscle remodeling at myotendinous junctions after modifications in muscle loading. AB - Modifications in muscle loading have been reported previously to result in increased numbers of mononucleated cells and changes in myofibril organization at myotendinous junctions (MTJs). The goals of this study were to determine the identity of those mononucleated cells and to examine the relationships between changes in their structure, location, and number with structural aspects of remodeling at MTJs experiencing modified loading. Soleus muscles from rats subjected to 10 days of hindlimb suspension were analyzed 0, 2, 4, and 7 days after return to weight bearing. Immunohistochemistry showed that ED1+, ED2+ and Ia+ macrophages were present at the MTJ and microtendon of control muscle. After reloading, ED2+ macrophages increased in number and size at MTJs and microtendons, indicating their activation. ED1+ cells showed no change in size or number whereas Ia+ cells were increased in size at day 7 of reloading. Electron microscopic observations showed that mononucleated cells near MTJs of control or suspended muscle were not highly active in protein synthesis or secretion. However, in reloaded muscle, mononucleated cells were found to be in close proximity to MTJs and to contain a high concentration of organelles associated with protein secretion. During these stages of reloading, extensive remodeling of myofibril-membrane associations occurred and nascent sarcomeres appeared in the MTJ regions of muscle fibers. Immunohistochemistry showed that during these stages of nascent sarcomere formation, there was renewed expression of developmental myosin heavy chain at MTJs, with this heavy chain appearing most prominently at the MTJ at day 7 of reloading. The activation and increased numbers of macrophages at MTJs and the close apposition of secretory cells to the MTJ membrane during remodeling lead us to propose that macrophage-derived factors may influence remodeling of MTJs in muscles experiencing modified loading. PMID- 7992850 TI - Influence of apolipoprotein E genotype on senile dementia of the Alzheimer and Lewy body types. Significance for etiological theories of Alzheimer's disease. AB - Alzheimer's disease (AD) is associated with an increased frequency of the apolipoprotein E type epsilon 4 allele. To address both the disease and the allele specificity of this association, we have examined the apolipoprotein E allele distribution in 255 elderly persons including those with autopsy-confirmed AD, senile dementia of the Lewy body type (SDLT), vascular dementia, Parkinson's disease (PD) or Huntington's disease and in nondemented controls either with or without coronary complications. The epsilon 4 allele frequency was increased in SDLT (0.365) and AD (0.328) as compared with controls (0.147), PD (0.098), or Huntington's chorea (0.171). Coronary disease and vascular dementia were associated with marginally higher epsilon 4 allele frequencies than in controls. In PD, amyloid beta-protein accumulated to a greater extent in those cases possessing an epsilon 4 allele than in those without. Those PD cases with dementia were not distinguished from either controls or PD cases without dementia, whether tested biochemically or by apolipoprotein E genotype. It is the comparison of the results in AD and SDLT that yielded the most significant findings. There was a 1.8-fold excess of amyloid beta-protein in AD as compared with controls, and the levels in SDLT were intermediate between those in AD and controls. In contrast, AD was discriminated from both controls and SDLT by the substantial accumulation of paired helical filament tau and phosphorylated tau (both increased more than 20-fold as compared with controls). SDLT was nevertheless characterized by an increased epsilon 4 allele frequency in the absence of significant tau pathology (at least 10-fold less than that in AD). These findings indicate that tau processing is more specifically associated with AD than is amyloid beta-protein accumulation and that presence of the epsilon 4 allele is not an etiological factor that accounts for tau pathology. PMID- 7992851 TI - Hematopoietic placental protein 14. An immunosuppressive factor in cells of the megakaryocytic lineage. AB - Placental protein 14 (PP14), an immunosuppressive molecule previously known to be expressed in the female and male reproductive tracts only, was shown to be expressed by hematopoietic cells of the megakaryocytic lineage. Northern blot analysis confirmed the induction specificity of PP14 mRNA in phorbol ester treated K562 cells. Potent immunosuppressive activity in conditioned medium from phorbol ester-treated K562 cells was attributed to hematopoietic PP14 by anti PP14 antibody blocking. Immunoprecipitation with anti-PP14 antibodies from conditioned medium revealed two distinct PP14 protein isoforms, designated PP14.1 and PP14.2. Polymerase chain reaction cloning and analysis demonstrated the presence of distinct mRNA counterparts to PP14.1 and PP14.2 that had not been resolved by Northern blot analyses. Hematopoietic PP14.1 mRNA corresponds in size to endometrial PP14 mRNA, whereas the smaller hematopoietic PP14.2 mRNA displays an internal in-frame 66-nucleotide deletion that can be explained by alternative splicing and predicts a 22-amino-acid deletion in the encoded gene product. Both PP14 mRNA isoforms were additionally detected by reverse transcriptase polymerase chain reaction analyses in two human megakaryocytic cell lines and in normal human megakaryocytes and platelets. PP14 mRNA was not detected by reverse transcriptase polymerase chain reaction in a panel of nonhematopoietic, nonendometrial tissues examined. The finding of hematopoietic PP14 within the megakaryocytic lineage provides an additional regulatory link between the coagulation and immune systems in normal and pathological settings. PMID- 7992852 TI - Ultrastructure and biochemical composition of paired helical filaments in corticobasal degeneration. AB - Corticobasal degeneration (CBD) is a neurodegenerative disorder associated with extensive cytoskeletal abnormalities. These include tau-positive neuropil threads and grains, ballooned or swollen neurons, neurofibrillary tangles, and glial inclusions. Given the presence of tau-positive structures in CBD, we investigated whether abnormalities in tau proteins associated with CBD were similar to those in Alzheimer's disease (AD). Fractions of abnormal tau proteins were isolated as Sarkosyl-insoluble pellets. By electron microscopic examination, the fraction from CBD contained twisted filaments that differed from paired helical filaments of AD. In CBD, filaments were shorter in length, rarely longer than 400 nm, 10 to 20% wider in the maximum and minimum widths (26 to 28 nm and 13 to 14 nm, respectively), and the periodic twist (169 to 202 nm) was twice as long as that in AD. Immunogold labeling with a panel of tau-reactive antibodies (Alz 50, Tau 14, AH-1, E-11, PHF-1, and Tau 46) showed no apparent differences in the pattern of tau immunoreactivity between filaments of CBD and AD. Western blots revealed that polypeptides of abnormal tau were present in both fractions; however, only two polypeptides (68 and 64 kd) were present in CBD as compared with three (68, 64, and 60 kd) in AD. Both of these polypeptides were reactive with additional antibodies (E-9, Tau-1 after dephosphorylation, AT8, and NP8). Only one polypeptide (68 kd) bound an antibody to adult-specific tau sequence encoded by exon 2, but neither was reactive with antibodies to adult-specific sequences encoded by exons 3 and 10. The results suggest that abnormalities in the number and heterogeneity of isoforms of tau may be one of the factors contributing to ultrastructural differences in pathological filaments of CBD and AD. PMID- 7992853 TI - Detection of human herpesvirus 6 and human papillomavirus 16 in cervical carcinoma. AB - A subset of human papillomaviruses (HPVs) is associated with the majority of cervical cancers; however, cofactors appear to be required for carcinogenic progression of HPV-induced neoplasia. As human herpesvirus-6 (HHV-6) was recently shown to infect cervical epithelial cells in vitro and activate transcription of HPV-transforming genes, human cervical dysplasia and cancers were analyzed for the presence of HHV-6 by multiple methods, including polymerase chain reaction, slot blot, Southern blot, and in situ hybridization. HHV-6 DNA sequences were detected in 6 of 72 cases of squamous cervical carcinoma and cervical intraepithelial neoplasia. HPV-16 was found in four of the HHV-6-positive cases (two squamous cervical carcinomas and two cervical intraepithelial neoplasias). None of the 30 normal cervices and biopsies of patients with cervicitis was positive for HHV-6 DNA. These results are the first suggestion of an in vivo association between HHV-6 and some cervical neoplasia. PMID- 7992854 TI - Thymic epithelial defects and predisposition to autoimmune disease in BB rats. AB - We report an association between thymic epithelial defects and predisposition to autoimmunity. Diabetes-prone (DP) BB rats develop spontaneous hyperglycemia and are deficient in T cell subsets expressing the RT6 alloantigen. Diabetes resistant (DR) BB rats become diabetic if depleted of RT6+ T cells. The inciting immune system defects are unknown. We made the following observations: 1) Regions of thymic cortex and medulla devoid of thymic epithelium exist in DP-BB, DR-BB, and Lewis rats, all of which are susceptible to autoimmune disorders. Such defects were absent in eight normal rat strains. 2) Thymic epithelial defects are absent at birth, but present in BB rats at 4 weeks of age. 3) The genetic predisposition to thymic epithelial defects is an autosomal dominant trait. 4) The observation of thymic defects in (DP x WF)F1 rats led to the prediction that such animals, which never develop spontaneous autoimmunity, might be susceptible to its induction. Following depletion of RT6+ T cells we observed diabetes in 91%, and thyroiditis in 43%, of treated F1 animals (n = 23). Pancreatic insulitis was uniformly present. Because thymic epithelium participates in the positive and negative selection of developing thymocytes, we propose that thymic epithelial defects may play an important role in the predisposition of BB rats to autoimmunity. PMID- 7992855 TI - Antibodies to the 280-kd coated pit protein, target of teratogenic antibodies, produce alterations in the traffic of internalized proteins. AB - Previous studies have identified two high-molecular weight (280 and 330 kd) glycoproteins expressed by coated pits of the proximal renal tubule and yolk sac and have further established that, in vivo, antibodies to gp280 but not to gp330 induce fetal malformations. In the present study, we report the effect of these antibodies on the endocytic process by yolk sac visceral epithelial cells of rat embryos explanted at day 10 of gestation. Antibodies to gp280 markedly altered development of the yolk sac and embryo, induced malformations, inhibited by 40% the uptake of [14C] sucrose and perturbed the intracellular traffic of internalized proteins. Under control conditions, rat immunoglobulin G present in the culture medium was immunolocalized in lysosomes of epithelial cells, whereas in the presence of antibody, it was detected in small vesicles scattered through the apical cytoplasm. Alterations of the endocytic pathway were confirmed by experiments analyzing the uptake of peroxidase added to the medium for 2 to 60 minutes. The initial compartments of endocytosis visualized by peroxidase were increased in size and abnormal in shape and the transfer of the internalized peroxidase to the lysosomal compartment was delayed. In contrast, antibodies to gp330 had a minimal effect on embryonic development and did not induce fetal malformations. Endocytosis was only modestly altered; uptake of [14C] sucrose was decreased by 25%, and only minor modifications of the intracellular transit of peroxidase could be detected. We suggest that the key role of anti-gp280 antibodies is via trapping of the target antigen in the early endocytic compartment thus preventing its normal function in lysosomal transfer. PMID- 7992857 TI - K-ras mutations in pancreatic ductal proliferative lesions. PMID- 7992858 TI - A Horneyan analytic perspective on couple therapy: a case study. AB - This paper describes the study, diagnosis, and course of treatment of a marital couple incorporating Horney theory as a basis for understanding. The case illustrates how fundamental features of Horney theory--character structure, pride positions, attacks on the idealized image, alienated aspects of self, externalization and counter-externalization-can be illuminated in the expanded context of a specific other, the spouse, as background. In a marriage characterized by conflict, omnipresent struggles for authority, and malignantly destructive communication, the wife adopts a position of self-effacement externalizing expansiveness to her husband while the husband adopts an expansive detached position externalizing both expansiveness and self-effacement to the wife. Externalizations from the wife include a form that has not been described in the psychoanalytic literature of the Horney school: indirect active externalization. As shown, the wife attributes an idealization of her husband to third parties. We observe, too, that the husband's reasonableness and the wife's emotional stridency have the effect of attacking the idealized image of the other. Defenses are mobilized in order to repair hurt pride reactions: for the husband, the wife's stridency is an assault on his sense of himself as a principled, virtous man. For the wife, the husband's reasonableness is experienced as an assault on her sense of herself as a caring wife and mother. In order to block their pride responses and attacks on each other's idealized image, which made conjoint sessions antagonistic and unproductive for a time, a "glass wall" technique was employed for some months that enabled each to speak to the other through me. I struggled against the temptation of siding with the husband's rationality and seeing the wife as secondary. I came to understand that the husband's reasonableness was oppressive for the wife. In order for the wife to feel understood empathically, I needed to fill the role of witness to her suffering over a long period of time. At the time this paper was prepared, I was attempting to explore the wife's fantasies and fears while supporting the husband's emerging self-affirmation and gradual recognition of how certain compelling dictates within himself require that his wife behave in a way that justifies certain externalizations as described above. A Horneyan perspective proves to offer a rich and practical theoretical framework to understand this clinical case, both in terms of diagnosis and treatment process. It enables the varieties of defensive maneuvers, particularly those connected to externalizing and idealizing, to be recognized, elucidated, and worked through in a systematic fashion.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7992856 TI - Replicative Legionella pneumophila lung infection in intratracheally inoculated A/J mice. A murine model of human Legionnaires' disease. AB - The role of host immune responses in the pathogenesis of Legionnaires' disease is incompletely understood, due in part to the current lack of an animal model that is both susceptible to replicative Legionella pneumophila-induced lung infection and for which species-specific immunological reagents are available. We have developed a model of replicative L. pneumophila lung infection in intratracheally inoculated A/J mice. L. pneumophila was obtained in the exponential growth phase and inoculated into the trachea of 6- to 8-week-old female A/J mice. Microbiological and histopathological evidence of infection was demonstrated in mice inoculated with 10(6) colony-forming units. Development of an acute pneumonia that resembled human Legionnaires' disease coincided with exponential growth of the bacteria in the lung 24 to 48 hours after intratracheal inoculation of L. pneumophila. This was associated with increased plasma levels of interferon gamma at 24 hours after inoculation. After 48 hours, the bacteria were gradually eliminated from the lung over the next 5 days, corresponding with resolution of the inflammatory response in the lung, thereby mimicking the outcome frequently seen in the immunocompetent human host. Treatment of animals with anti-interferon gamma antibody enhanced bacterial replication and disease progression, indicating an important role of host immune response in resolution of the infection. Because of the availability of murine-specific reagents, this model of replicative L. pneumophila lung infection in A/J mice after intrapulmonary inoculation of L. pneumophila potentially provides an important tool for future studies investigating the role of host immune responses in the pathogenesis of Legionnaires' disease in the immunocompetent host. PMID- 7992859 TI - It's not such a wonderful life: the neurotic George Bailey. PMID- 7992860 TI - Feedback in dynamic psychotherapy: definitions and essential concepts. PMID- 7992861 TI - The use of a psychoanalytic framework in the rehabilitation of patients with traumatic brain injury. PMID- 7992863 TI - Fantasies about Freud's fantasies. PMID- 7992862 TI - Cross-cultural passages. PMID- 7992864 TI - Legacy for our children: violence or harmony? PMID- 7992865 TI - Therapeutic approaches to delinquency: the negative ideal. PMID- 7992866 TI - Self-destructiveness in adolescence. AB - This study is an attempt to formulate the dynamics of the group of adolescents involved in major drug use and other antisocial behavior. As consultant to a drug rehabilitation center for teenagers, the author has had occasion to interview and evaluate a large number of youths whose lives had taken such a turn. Certain aspects of the life style and behavior patterns of these young people show striking similarities. In particular, their behavior evidences the presence of a central self-destructive moiety which can be likened to a negative ego ideal; this acts to shape and to direct their lives. This element in the character structure of these patients is described in clinical and theoretical (developmental) terms, with special address to: a chronic low-grade sense of inner malaise, a tendency to self-blame for whatever goes wrong for family and close friends, feelings of alienation from the larger society around them, behavioral provocativeness in the service of seeking the relief that punishment brings, recurrent gestures of self-mutilation, frequent involvement with cults of devil worship, a record of multiple antisocial acts punctuated by numerous arrests, and repeated suicidal gestures and attempts. The origins of the negative regulatory superego elements which make for this type of psychopathology are explored. PMID- 7992867 TI - Self-destructiveness in adolescence: psychotherapeutic issues. AB - In sum, then, the psychotherapy of self-destructive adolescents involves an assessment of the degree to which the patient's behavior is dominated by a negative ideal. If that seems like a central mechanism, than the therapist must seek ways to bring this to awareness, to confront the patient with the presence and the activity of such a component of the self, to sensitize the patient to the way this expresses itself in his everyday behavior, and to rally the patient to the twin tasks of facing this and consciously opposing it, and of working to discern its origins and what happened to introduce it into his life. Generally speaking this is an aspect of personality that patients tend to repress and to maintain in repression. They may do this by denial, evasion, or hyper emotionality, by regarding this part of the self as a source of pleasurable excitement, or by using its effects to drive away the therapist or to convert the therapy into yet another site for the attainment of pain, frustration and failure. PMID- 7992868 TI - Psychologists' beliefs concerning confidentiality with suicide, homicide, and child abuse. AB - A large number of psychologists from the Division of Psychotherapy and the Division of Psychologists in Practice were surveyed to determine their attitudes about confidentiality. It was found that psychologists reference their personal code to a considerable extent when making decisions about breaching confidentiality and when providing information to their clients about confidentiality. Approximately one-fourth of the respondents believed in absolute confidentiality. These respondents were found to differ from those respondents who did not believe in confidentiality with respect to their actions as therapists, their beliefs about the effects of informing clients concerning limits of confidentiality, and their actually breaching of confidentiality. The two groups differed much less with reference to items that assessed knowledge of matters pertaining to confidentiality, as well as information afforded their clients. Possible stress and conflict experienced by those believing in absolute confidentiality, in light of legal and APA mandates, is discussed along with the need for future research. PMID- 7992869 TI - Object relations theory and pharmacopsychotherapy of anxiety disorders. AB - This paper provides an overview of object relations concepts, applying them specifically to combined psychoterapy-pharmacotherapy of anxiety disorders. Anxiety in this clinical theory is conceptualized as arising from threatened loss of the self- and object-relationship. At a rudimentary level, individuals can attempt to manage potential loss through splitting and projective identification. As benign and loving experiences accumulate and ego functions neurophysiologically develop, whole object relations provide alternate and more modulated ways of coping with anxiety. In anxiety disorders, these more mature coping styles break down. Treatment combining object relations approaches to psychotherapy with pharmacotherapy pay particular attention to the relationship aspects and meanings of medication and prescribing. These approaches use the concepts of empathy, containment, countertransference, splitting, projective identification, and transitional object formation to help patients come to terms with their anxiety and with the treatment relationship. PMID- 7992870 TI - Treatment for multiple personality disorder: at what cost? AB - The material presented in this paper suggests that before mental health practitioners ask of society the resources to treat those thousands of patients diagnosed with MPD in the past few years, a critical attempt should be made to evaluate the efficacy of the type of treatment currently recommended for the condition. Proponents of the disorder claim its treatment is cost-effective, but this article's analysis indicates that it is simply premature to make claims about the treatability or prognosis of multiple personality disorder. PMID- 7992871 TI - Adaptive function of depression: psychotherapeutic implications. AB - Using the frameworks of attachment and social hierarchy theories, strategies seen in depression and in normal life are better understood. A hierarchial encounter elicits the "Involuntary Subordinate Strategy" ("ISS") in the loser, which terminates the "ISS" and brings the encounter to an end. These are psychophysiological mechanisms deeply rooted in our phylogenetic ancestry. Loss of a love object also elicits ineffective anger or rage which may, in turn, trigger the ISS. A prolonged intense ISS manifests in depression. Factors are examined that prevent "acceptance" of losing, thereby contributing to an escalation of the ISS and culminating in depressive illness. Psychotherapeutic implications include cognitive restructuring to enable the patient to explore options that might turn off the ISS such as "acceptance" (without making negative self-evaluations), changing unrealistic ideals and aspirations, leaving the scene, or becoming more self-assertive. Case examples are given to illustrate these interventions. PMID- 7992872 TI - The supervision of psychotherapy supervisor trainees. AB - Corresponding to the four stages of the SCM, supervision environments/behaviors- which could be used to guide thinking about the supervision of psychotherapy supervisor trainees--have been proposed and described. The supervision environments are designed to match the particular needs of psychotherapy supervisors at the four SCM stages. From this presented conceptualization, the reader can see that the supervision of psychotherapy supervisor trainees proceeds through (1) an initial period where a strong, secure "hold" and direct instruction, teaching, and structure are needed, to (2) a period where a continued but loosened "hold" and continued but lessened instruction, teaching, and structure are needed, to (3) a period where an even greater loosening occurs and a shift to more of a collegiate/collaborative stance evolves, to (4) a period where a collegiate/collaborative stance totally predominates. PMID- 7992873 TI - Limit setting: theory, techniques, and risks. AB - Limit setting is a necessary aspect of clinical treatment but the professional literature on this subject is relatively sparse and does not address many core issues, including some countertransferential and ethical problems raised by the approach. Many clinicians struggle with the "authoritarian" nature of limit setting, especially when they have great power over patients as in a hospital setting. This paper traces the theory of limit setting back to Freud's conception of "acting-out in the transference" and the corresponding need by clinicians to manage nihilistic behavior which threatens the treatment process, whether inpatient or outpatient. When done properly, setting limits makes working with acting-out patients viable, enabling them both to master devastating early experiences and to replace restraint by others with self-control. Techniques are addressed which lead to the responsible and effective use of power, but at the same time observing the social and practical limits inherent in the approach. PMID- 7992874 TI - Political attitudes and religiosity levels of Israeli psychotherapy practitioners and students. AB - This study investigated the political attitudes (PA) and religiosity level (RL) of a practitioners sample, comprising 82 psychiatrists, 222 clinical psychologists, and 113 psychiatric social workers, and a students sample comprising 69 B.A. and 65 M.A. students in psychology, and 73 B.A. students in social work, who intended to practice psychotherapy. PAs were measured by the subjects' voting intentions, self-definition, and attitudes toward Capitalism Socialism and the occupied territories. RL was judged by special measures developed for the Jewish population in Israel, which were adapted for secular psychotherapists. Subjects also defined both themselves and their parents regarding PA and RL. The results are similar to findings of previous studies, indicating that psychotherapists support the political left and conduct a secular way of life. No significant differences were found between practitioners and students regarding PA and RL. A significant decrease in subjects' right-wing attitudes and RL relative to their parents was found. It is suggested that the similarity between practitioners and students regarding PA and RL could imply that supporting the political left and low RL preceded the decision to practice psychotherapy. The therapeutic implications of the differences between therapists and clients regarding PA and RL are also discussed. PMID- 7992875 TI - Integrating African and Western healing practices in South Africa. AB - Through a detailed analysis of a dream shared by three adolescent girls suffering from PTSD, this paper has outlined many similarities between an African and a Western understanding of their symptoms. It has shown how both systems would acknowledge these symptoms to be a function of: (a) the breaching of stimulus boundaries; (b) the existence of survivor guilt; (c) the phenomenon of frozen mourning. It has illustrated further how many factors considered to be part of Western psychotherapy, e.g., (a) catharsis following an emotional reliving of the traumatic event; (b) re-ordering of perceptions following insight; (c) fostering hope for the future following a re-establishment of continuity with the past, may be promoted while interpreting dreams within the traditional meanings ascribed to them by an African healing framework. That is, it has been shown how these elements may be fostered while working within the African belief that dreams are not the manifestation of intrapsychic conflict but communications from ancestral spirits concerning interpersonal duties that need to be fulfilled. Finally this paper has illustrated the importance of therapists developing a general appreciation of myths and metaphors. PMID- 7992876 TI - Potentiometric thick-film sensor for the determination of the neurotransmitter acetylcholine. AB - A potentiometric thick-film biosensor for the determination of the neurotransmitter acetylcholine is presented. The selective membranes consist of two layers. The first is a choline- and H(+)-selective membrane made from a poly(vinyl chloride)-poly(vinyl acetate) copolymer which is plasticized with 2 nitrophenyl octyl ether. It contains 1% m/m of the ion-pair choline phosphotungstate as an electroactive compound. Both products of the enzymic cleavage, choline and H+, are detected. The second layer is placed above the first and is made from a poly(vinyl acetate)-polyethylene dispersion polymer. It is loaded with 2% m/m of acetylcholinesterase isolated from electric eel. The linear region of the response curve extends from 2 x 10(-5) to 0.01 mol dm-3 in buffer solution and undiluted horse serum. The detection limit is 5 x 10(-6) mol dm-3 and the response time is about 4 min. PMID- 7992878 TI - Sensitive method for measuring lactate dehydrogenase activity in human serum by differential-pulse polarography. AB - A sensitive and accurate differential-pulse polarographic method is reported for the measurement of lactate dehydrogenase (LDH) activity. The method is based on the polarographic measurement of the NAD+ formed via the enzymic reaction of LDH with pyruvate and NADH. The method was successfully applied to measure LDH activity in the serum of normal and diseased individuals. PMID- 7992877 TI - Determination of selenium in food supplements by differential-pulse cathodic stripping voltammetry in the presence of added copper. AB - Selenium was determined by cathodic stripping voltammetry in a 1 mol l-1 HCl acid solution containing added CuII. In this medium, selenium was preconcentrated on the hanging mercury drop electrode and stripped cathodically in differential pulse mode. After a deposition period of 1 min, 0.2 ng ml-1 of selenium could be detected. The method was applied to the analysis of food supplements. Total selenium was determined after digestion of the sample with HNO3-HClO4 and reduction to the electroactive SeIV by heating with HCl. Inorganic selenium (i.e., selenite and selenate) was similarly determined after extraction with dilute sodium hydroxide solution and clean-up on activated carbon. Representative over-the-counter preparations have been analysed. PMID- 7992879 TI - Development of a radioimmunoassay for the determination of N-desmethylzopiclone in urine. AB - The development of a specific and sensitive radioimmunoassay for the detection of N-desmethylzopiclone in urine samples is described. The assay will be used to pre screen for N-desmethylzopiclone as an indication of zopiclone intake in a forensic and emergency context. N-Hemisuccinyldesmethylzopiclone has been prepared as a hapten. The immunization of rabbits with the hapten-bovine serum albumin conjugate resulted in the production of highly specific antibodies, showing no significant cross-reactivities with existing drugs. The four-parameter logistic model was used to process the calibration data into a fitting curve (r2 = 0.9979). Intra- and inter-assay relative standard deviations were < 9.1 and < 19.1%, respectively. The minimum detectable dose of the immunoassay was calculated to be 0.1 ng ml-1 (Pooled-variance t-distribution, p = 0.01, degrees of freedom = 14). PMID- 7992880 TI - Application of the matrix solid phase dispersion technique for the determination of ivermectin residues in fish muscle tissue. AB - A modified high-performance liquid chromatographic method has been developed for the determination of ivermectin (IVM) residues in fish muscle tissue. The extraction and clean-up procedure is based on the matrix solid phase dispersion technique. Control and IVM-fortified fish muscle samples (0.5 g) are blended with octadecyl (C18 end-capped) packing material. A column made from the C18-fish tissue blend is washed with hexane (8 ml) and the IVM is eluted with 8 ml of dichloromethane-ethyl acetate (3 + 1). Ivermectin is derivatized and analyzed by high-performance liquid chromatography (HPLC) with fluorescence detection. The recovery from fortified samples was greater than 80% in the concentration range 20-100 ng g-1 of tissue. The limit of determination was 10 ng g-1 of tissue. This method and another, using solvent extraction and clean-up of the extract on a solid phase extraction cartridge, gave comparable results for an incurred sample containing IVM residue. This method incorporates a rapid sample pre-treatment step which makes it an attractive and useful method for routine analysis of IVM in fish muscle tissue. PMID- 7992881 TI - Ultrastructural differentiation of the first Hensen cell in the gerbil cochlea as a distinct cell type. AB - BACKGROUND: The mammalian cochlea contains beneath and lateral to outer hair cells, several types of supporting cells. The function of these cells has not been explained beyond providing a structural base. METHODS: The supporting cells of gerbil cochlea were examined by electron microscopy with a view to elucidating their biologic activity on the basis of cytologic structure. RESULTS: Ultrastructural examination differentiated the laterally located Hensen cells from their medial neighbor connected to the third Deiters cell. The latter cell formed a cover to the outer tunnel between Hensen and Deiters cells, appeared not to reach the basilar membrane, and exhibited a denser cytosol and more mitochondria, compared to Hensen cells. In these respects the cell observed here to cover the outer tunnel, corresponded with the tectal cell described by Henson et al. (1983) in the mustache bat, but not heretofore documented in other animals. CONCLUSIONS: This distinctive cell in the gerbil differed in displaying unique villus-like structures which projected from the basomedial surface and are referred to as fimbriae. The fimbriae and interspersed filopodia largely filled outer tunnel space and expanded the cell's basal surface. The amplification of basal plasmalemma by fimbriae and their content of mitochondria testify to a role for the tectal cell in ion resorption and an influence on ion content and volume of outer tunnel fluid. PMID- 7992882 TI - Ultrastructural evidence for innervation of the endothelium and interstitial cells in the atrioventricular valves of the Japanese monkey. AB - BACKGROUND: A rich supply of nerves to the atrioventricular valve has been demonstrated. The role of the valvular nerves is still controversial because the target sites of the nerves have not been confirmed. METHODS: The innervation of the atrioventricular valves of the Japanese monkey (Macaca fuscata) was examined by acetylcholinesterase staining and electron microscopy. Immunoreactivity for neuropeptide Y (NPY) was also investigated by a post-embedding immunogold method. RESULTS: The valvular nerve elements were clearly concentrated between the endothelium and interstitial cells on the atrial side of cusps. Naked axon terminals were observed to make direct contact (20-nm gaps) with interstitial cells and also to be in close proximity (approximately 200-nm cleft) to the endothelium. NPY immunoreactivity was clearly detected on the large granular vesicles in some terminals that were in close proximity to interstitial cells and/or the endothelium. CONCLUSION: The present study suggests that the extensive innervation of the atrioventricular valve, which includes NPY-containing nerves, might affect valvular function via interstitial cells and/or the endothelium. PMID- 7992883 TI - Ultrastructure and histochemistry of human anterior lingual salivary glands (glands of Blandin and Nuhn). AB - BACKGROUND: Specimens of human anterior lingual salivary glands obtained by surgery and by dissection of cadavers were studied ultrastructurally and histochemically. METHODS: Specimens were obtained by surgery for ultrastructural study. Other specimens for histochemistry were obtained by dissection of fresh cadavers. Tissues for electron microscopy were fixed and processed by conventional means. Formalin-fixed cadaver specimens were subjected to a battery of tests for glycoconjugates. RESULTS: The anterior lingual salivary glands are composed predominantly of mucous tubules (which come in two distinct sizes: large and small), seromucous demilunes, and rare seromucous acini. Regardless of tubule size, mucous cells are typical in appearance and, like mucous cells in other human salivary glands, contain filamentous bodies. Histochemically, the larger tubules contain neutral glycoproteins, low concentrations of sialoglycoproteins, and large amounts of sulfated glycoproteins. The small mucous tubules contain neutral glycoproteins, much sialoglycoprotein, and relatively small amounts of sulfated glycoprotein. The seromucous cells, whether demilunar or acinar, are identical. They contain numerous secretory granules, which show a spectrum of internal patterns from one individual to another. These cells have considerable concentrations of neutral- and sialoglycoproteins and lower concentrations of sulfated glycoproteins. Contrary to previously published reports, we could find no differences in the ratio of mucous to seromucous cells along the anterior posterior lingual axis: there was no gradient of seromucous cells in our specimens. The ducts in the anterior lingual salivary glands are not precise counterparts of those in the major salivary glands, since the former have no capsules, hence lack lobulation. Without these familiar structural landmarks, the only duct that can be identified with certainty is the intercalated duct, and then only if it is in continuity with or lies close to a secretory endpiece. Such ducts consist of simple cuboidal epithelium of prosaic appearance. The ductular epithelium gradually thickens and gives rise to what appear to be excretory ducts consisting of columnar cells with few mitochondria. Scattered within the walls of the larger ducts are patches of typical striated ducts wherein the taller cells display basal striations resulting from highly folded basal plasma membranes and numerous, vertically oriented, virgulate mitochondria. In other atypical regions of the excretory duct, basal cells may have a primary cilium that juts into the intercellular space. CONCLUSIONS: There is a high degree of structural variability in human anterior lingual salivary glands. Because of the technical difficulties in collecting pristine saliva from these glands, the precise function(s) of these organs remains unknown. PMID- 7992884 TI - Mucous droplets with multiple membranes in the accessory submandibular glands of long-winged bats. AB - BACKGROUND: Certain species of bats possess two sets of submandibular glands, namely, principal and accessory. The ultrastructure and histochemistry of the accessory submandibular gland was examined in three species of long-winged bats. METHODS: Specimens of Miniopterus schreibersi and M. magnator were live-trapped in Thailand, and of M. inflatus were live-trapped in Kenya. For electron microscopy, accessory submandibular lands were initially fixed in triple aldehyde DMSO, postfixed in osmium tetroxide, and embedded in Epon-Maraglas. A portion of the glands collected in Thailand (M. schreibersi and M. magnator) was fixed in buffered formalin and embedded in paraffin. Sections of the latter material were subjected to a battery of histochemical tests for glycoconjugates. RESULTS: Although in all three species the accessory submandibular glands have normal histological structure, the glands in two, M. schreibersi and M. magnator, were distinguished by possessing mucous droplets of unusual morphology. These droplets, whose identity as mucous was confirmed by histochemical tests for glygoconjugates, are delimited by manifold membranes: up to 10 in M. schreibersi and fewer, but still multiple, in M. magnator. In both species, the entire array of surface membranes may fold inward in the fashion of mitochondrial cristae, forming packets of membranes, many of which have the spurious appearance of floating free in the droplet matrix. These multipartite limiting membranes appear to originate simply by Golgi saccules and moderately large, flattened Golgi vesicles repeatedly wrapping themselves around the surface of nascent mucous droplets. During exocytosis, the outermost membrane of each mucous droplet contacts the luminal membrane, this barrier ruptures, then the remainder of the droplet--multiple membranes and matrix--either flow into the lumen or are cast out in toto. In either case, a great deal of membrane phospholipid is added to the saliva. This salivary lipid may permit these bats to consume insects that normally are able to repel predators with chemical defenses that make them unpalatable. The third species that we studied, M. inflatus, has mucous droplets of normal appearance, i.e., they have only one limiting membrane. CONCLUSIONS: The varying structure of mucous secretory products among the species of Miniopterus provides important clues as to the evolution of this genus as well as to the evolution of secretory cells in general. PMID- 7992885 TI - Light and TEM study of nonregenerated and experimentally regenerated scales of Lepisosteus oculatus (Holostei) with particular attention to ganoine formation. AB - BACKGROUND: The structure of nonregenerated and experimentally regenerated scales of the holostean fish Lepisosteus oculatus and the events taking place before and during ganoine deposition on the scale surface were studied. The aim of this study was to answer the question of the origin of the ganoine in lepisosteids, the scales of which are devoid of dentine, and to compare them to ganoine formation in polypterid scales and to enamel formation in teeth. METHODS: Two adult specimens were used and the scale structure was studied using light and transmission electron microscopy. Regeneration was used as an alternative to the lack of developmental stages and to induce ganoine deposition on the scale surface. RESULTS: Nonregenerated scales are composed of a thick, avascular bony plate capped by ganoine that is covered either by the epidermis or by dermal elements. The ganoine surface is separated from the covering soft tissues by an unmineralized layer, the ganoine membrane. During the first 2 months of regeneration, the bony plate forms. It differs from the bony plate of nonregenerated scales only by its large, woven-fibered central region and by the presence of numerous vascular canals. Shortly before ganoine deposition, the osteoblasts cease their activity and an epithelial sheet comes to contact them and spreads on the bony surface. This epithelial sheet is connected to the epidermis by a short epithelial bridge only and is composed of two layers: the inner ganoine epithelium (IGE), in contact with the bone surface and composed of juxtaposed columnar cells that synthesize the ganoine matrix, preganoine; the outer ganoine epithelium (OGE), composed of elongated cells, the surface of which is separated from the overlying dermal space by a basal lamina. Isolated patches of preganoine are deposited by the IGE cells in the upper part of the osteoid matrix of the scale. The interpenetrated preganoine and osteoid matrices constitute an anchorage zone between ganoine and bone. Preganoine patches fuse and a continuous layer of preganoine is progressively synthesized by the IGE cells. Preganoine progressively mineralizes to become ganoine. CONCLUSIONS: The processes of ganoine formation are similar to those known for the ganoine in the polypterid scales and to those described for enamel deposition in teeth. Ganoine is enamel. PMID- 7992886 TI - Changes in proteoglycans of ageing and osteoarthritic human articular cartilage: an electron microscopic study with polyethyleneimine. AB - BACKGROUND: Ageing and osteoarthritic (OA) cartilage show characteristic alterations in chondrocyte morphology and in the composition and content of matrix proteoglycans (PGs). Data concerning matrix components are mostly of biochemical nature. Ultrastructural histochemistry is needed to gain more information about distribution of these altered matrix components. METHODS: We used the cationic dye polyethyleneimine (PEI) to visualize at the EM level alterations in the distribution and dimensions of PGs of human healthy young, healthy aged, and OA articular cartilage. RESULTS: Young cartilage contained PEI positive granules in the superficial layer and big winding PEI-positive structures in the deeper layers. In the healthy aged tissue, PEI-positive granules were observed throughout the matrix and smaller winding structures were present in the deeper layer. In OA cartilage both types of PEI-positive structures were absent in the superficial layer. Deeper in the matrix PEI positive granules could be demonstrated. Moreover, PEI-positive angular structures were observed in the deeper zones. CONCLUSIONS: The differences in PEI positive structures are a good reflection of the differences in PGs between young, ageing, and OA cartilage as demonstrated in biochemical studies. PEI, used at the EM level, gave more precise information concerning the localized changes in quality, quantity, and location of PGs in articular cartilage during ageing and disease. PMID- 7992887 TI - Appearance of complex branched fibers following repetitive muscle trauma in normal rat skeletal muscle. AB - BACKGROUND: To examine whether the complex branched fibers observed in mdx mutant mice were formed in normal skeletal muscles, long-term repetitive muscle trauma was applied to muscle of normal Wistar male rats. METHODS: Three kinds of artificial muscle trauma--crush injury, bupivacaine hydrochloride treatment, and forced stretching of contracting muscle (eccentric contraction)--were performed once a week for 10 weeks to achieve a state of repetitive degeneration and regeneration in the muscles. Two weeks after the final treatment, numerical, histochemical, and three-dimensional analyses by scanning electron microscopy were performed. RESULTS: Mean numbers of total branched fibers of the three groups were increased compared with normal control values, especially in the bupivacaine treatment group (three- to fivefold greater than in the other two groups). Aggregations of fibers of the same type which usually appear in mdx mice were observed in various parts of histological sections of the bupivacaine treatment group and only in a part of the crush injury group. No aggregations were observed in sections of the forced stretching group. In the three dimensional analysis, complex branched fibers appearing as an "anastomosing syncytial reticulum" were observed only in the bupivacaine treatment group. CONCLUSIONS: These findings suggest that the formation of an anastomosing syncytial reticulum is one of the adaptation mechanisms of normal skeletal muscle rather than a specific event in mdx mutant mice, and long-term repeated trauma of the same fiber is necessary for this formation. Adaptive changes in the muscles with the three different types of muscle trauma are discussed. PMID- 7992888 TI - Sertoli cells in testes containing or lacking germ cells: a comparative study of paracrine effects using the W (c-kit) gene mutant mouse model. AB - BACKGROUND: Paracrine effects of germ cells on Sertoli cell structure were examined in a mouse model with the W locus (dominant white spotting) mutation in which animals with the W/Wv genotype (referred to as mutants) lack virtually all germ cells. RESULTS: Morphometric determination of Sertoli cell parameters in mutant and control (+/+) animals showed that although the testes of mutant animals were about eight times smaller than controls, the numbers of Sertoli cells in the two groups did not differ. Sertoli cell volume, Sertoli cell cytoplasmic and nuclear volumes, and Sertoli cell surface area in mutant animals were significantly smaller than in control animals. Organelle volumes and surface areas, expressed per cell, did not differ significantly in the two groups with one exception: the volume and surface area of smooth endoplasmic reticulum was significantly reduced in mutant animals. Plasma testosterone levels and tissue testosterone levels/testis were normal, indicating that the effects observed in the mutant animal were not a consequence of androgen insufficiency. Plasma FSH was elevated, probably as a consequence of germ cell depletion, and was thought not to affect Sertoli cell parameters observed. CONCLUSIONS: The data suggest that paracrine interactions with germ cells do affect Sertoli cells by modifying the amount of smooth endoplasmic reticulum. These data focus attention on the function of this abundant Sertoli cell organelle in promoting spermatogenesis. PMID- 7992889 TI - Distribution of macrophages in the mouse uterus from one day to three months after parturition, as defined by the immunohistochemical localization of the macrophage-restricted antigens F4/80 and macrosialin. AB - BACKGROUND: The morphology of placental detachment sites and the distribution of macrophages were studied in the mouse uterus from day 1 to 3 months post partum. METHODS: Uterine morphology was studied using H&E and Mallory's Trichrome staining. Macrophages were identified using the macrophage-restricted antigens F4/80 and FA/11 and the leukocyte beta 2-integrin CR3 (Mac-1) which is also expressed by neutrophils. RESULTS: The post-partum wound was infiltrated by large numbers of CR3+ F4/80+ FA/11+ macrophages, and CR3+ neutrophils. The wound resolved rapidly and no inflammatory infiltrate or necrotic tissue was seen by day 5 post partum. The area of the detachment wound and the site of the metrial gland of pregnancy resolved into a structure, here called a post-partum nodule, which persisted for at least three months. The post-partum nodule consisted of an outer layer of collagen around a group of nodule-specific cells which could be divided into haemosiderin- and lipid-bearing phenotypes. The lipid-bearing nodule cells were not found after day 20 post partum. Nodule cells were FA/11+ at all times and also expressed leukocyte common antigen. Expression of CR3 and F4/80 was found on nodule cells up to day 9-10 post partum. CR3 expression was found only occasionally after day 10. F4/80 expression was downregulated from day 9-10 to day 20 but was found consistently after day 20. Implantations of second and subsequent pregnancies are known not to occur in the immediate vicinity of post partum nodules and nodules from successive pregnancies were seen to be separate within the uterus. CONCLUSIONS: Since the endometrial area in the immediate vicinity of nodules is inimical to implantation and nodules consist of a group of macrophages, it can be implied that nodule macrophages are exerting some influence on the endometrium in their vicinity. PMID- 7992890 TI - Cartilago cordis in serpents. AB - BACKGROUND: The cartilago cordis, a cartilaginous element present within the heart, has been found in a number of vertebrates. The present study provides a detailed description and comparative analysis of the cartilago cordis in snakes. METHODS: Transverse sections through the hearts of 42 snakes and three monitor lizards were examined. RESULTS: A cartilago cordis was found near the roots of the aortic trunk and pulmonary artery in eleven species of snakes. There is substantial variation in the size, shape, and precise location of the cartilago cordis. CONCLUSIONS: The presence of a cartilago cordis does not correlate with body size, taxonomic relationships, or habitat preference. The cartilago cordis may simply represent an illustration of the potential for chondrification that is present in the connective tissue of the aorticopulmonary septum. PMID- 7992891 TI - Perinotochordal connective sheet of gilthead sea bream larvae (Sparus aurata, L.) affected by axial malformations: an histochemical and immunocytochemical study. AB - BACKGROUND: Spinal malformations in adult teleosts occur under natural conditions and, more frequently, in culture exploitations. Skeletal deformities are linked with dysfunctions in collagen metabolism. We studied axial deviations appearing in early larval stages of cultured sea bream (Sparus aurata, L.). METHODS: To evaluate connective tissue components of normal and lordotic fish we used histochemistry (alcian blue, picrosirius-polarization, clorhydric orcein, fuchsin resorcin), immunohistochemistry (anti-collagen I, II, III, and IV), and specific enzymatic digestions. The results were evaluated by semiquantitative methods. RESULTS: Lordosis appeared before a vertebral column was developed, thus affecting the only skeletal structure present in the animal body, the notochord. At this stage the animal depends on the vitelline sac and an inflated swim bladder is missing. The region of the curvature showed strong alterations in the arrangement of the muscle bundles and irregularities in notochord and perinotochordal collagen sheet. Histochemical and immunocytochemical analysis of the perinotochordal sheet revealed the presence of type II collagen, non-sulfated glycosaminoglycans, and elastic fibers in normal and lordotic specimens. Low collagen-proteoglycan interactions occurred in lordotic animals. CONCLUSIONS: Lordosis in Sparus aurata originated during embryonic development and was characterized by disorganized connective tissue and muscle bundles. No major differences in connective tissue constituents were seen with respect to normal specimens. PMID- 7992892 TI - Immunohistochemical evidence of neurons with GHRH or LHRH in the arcuate nucleus of male mice and their possible role in the postnatal development of adenohypophysial cells. AB - BACKGROUND: The neonatal administration of monosodium L-glutamate (MSG) has been used in investigations of the possible role of the arcuate nucleus in neuroendocrine regulation during postnatal development. We used this method to examine whether the mouse arcuate contained cell bodies immunoreactive with antisera to growth hormone releasing hormone (GHRH) or luteinizing hormone releasing hormone (LHRH), and whether these hypothalamic peptides affect synthesis and secretion of growth hormone and gonadotropin and the testis. METHODS: The hypothalamus, pituitary, and testes of adult male mice treated with MSG during the neonatal period were fixed in Bouin's fluid or 10% neutral formalin. The hypothalamus was used in immune staining, the pituitary was used in both morphometry and immune staining, and the testis was stained with hematoxylin and eosin. RESULTS: Body weights in control and treated mice were not different. The treated mice had more subcutaneous adipose tissue and a shorter body than the control mice. The testes were heavier in the controls. Many perikarya immunoreactive with antisera to GHRH or LHRH were found in the arcuate nucleus in control mice, but few such perikarya were found in this nucleus in treated mice. The size of the anterior lobe and the number and size of GH cells, follicle stimulating hormone (FSH) cells, and prolactin (PRL) cells in treated mice were less than those of control mice. CONCLUSIONS: GHRH and LHRH neurons in the arcuate nucleus in male mice may cause body and testis weight to increase via GH and LH cells, respectively, in the adenohypophysis during postnatal development. There are some differences in the hypothalamo-pituitary-testis axis of mice and rats. PMID- 7992893 TI - Abandonment of germ cells in the embryonic chick ovary: TEM and SEM studies. AB - BACKGROUND: Embryonic chick ovary forms medulla and cortex successively in early developmental stages. Unlike the cortex, which is a functioning tissue in the adult, the medulla regresses as development advances. Although germ cells are included in these respective regions, their behavior within these regions is different. This study focuses on the fate of germ cells in the medulla of both ovaries. METHODS: Germ cells found in the medulla of the developing chick ovary from 7 to 19 days of incubation were observed by TEM and SEM. RESULTS: From 10 days of incubation onward, medullary germ cells in both right and left ovaries were often released into medullary lacunae. During the releasing process, germ cells were covered by thin cytoplasm of epithelial cells of the lacunae. After release, however, they were freed from the thin coat of epithelial cells. Abandoned germ cells were seen in the lacunae as solitary cells or as a mass composed of several cells. In the right ovary, germ cells released into the lacunae were subsequently found at the holes of the ovarian surface, which were continuous with the medullary lacunae. Moreover, germ cell death was often found in late stages in the medullary tissues of both right and left ovaries. CONCLUSIONS: The present study clarifies the fact that chick germ cells of the medulla of both right and left ovaries are either discarded by a process of programmed cell death and/or released into medullary lacunae with increasing embryo age. PMID- 7992894 TI - Differentiation of the chorionic plate of the placenta: cellular and extracellular matrix changes during development in the macaque. AB - BACKGROUND: The chorionic plate forms the fetal side of the placental disc, and its proper growth and development is important to the formation of a normal placenta. The development and structure of the chorionic plate has received little attention. Therefore, we have conducted a developmental and immunohistochemical study of the chorionic plate of the macaque placenta. METHODS: Conventional light and transmission electron microscopy techniques were used to study macaque placental tissues collected from 22 days of gestation to near term. Standard immunoperoxidase methods were used to identify type IV collagen, laminin, and fibronectin in paraffin sections. RESULTS: Early in gestation the chorionic plate trophoblast consisted of an outer layer of syncytiotrophoblast and a single underlying layer of cytotrophoblast. Beginning at about 100 days of gestation, the cytotrophoblast layer became stratified. The cytotrophoblast cells also became surrounded by variable amounts of extracellular matrix containing type IV collagen, laminin, and fibronectin. Ultrastructurally, the matrix contained abundant 10-12 nm diameter microfibrils. During later gestation the syncytiotrophoblast had a tendency to separate from the cytotrophoblast. CONCLUSIONS: The chorionic plate of the macaque placenta undergoes several distinctive morphological changes over the course of gestation. During the period of rapid diametrical growth of the disc, the chorionic plate trophoblast consists of a layer of syncytiotrophoblast and a single layer of cytotrophoblast. During later gestation the cytotrophoblast layer stratifies at a time coincident with that at which diametrical growth of the disc slows. The cytotrophoblast cells of later gestation appear synthetically active and at least some of their products are extracellular matrix components that encapsulate many of these cells. These components include type IV collagen, laminin, fibronectin, and microfibrils. PMID- 7992895 TI - Structural, morphometric, and immunohistological study of the accessory olfactory bulb in the dog. AB - BACKGROUND: The study of the morphological, morphometric, and immunohistological characteristics of the accessory olfactory bulb (AOB) in the dog is the main goal of this work. METHODS: Horizontal sections of the AOB where stained by four different methods (haematoxilin/eosin, Tolivia, Nissl, and Bielchowsky). The avidin-biotin-peroxidase complex (ABC) was used, whereas the monoclonal antibodies to neuron-specific enolase, neurofilaments, glial fibrillary acidic protein, and synaptophysin were selected for the immunohistological study. A computer-assisted image analysis was employed in order to define the morphometric characteristics of de AOB. RESULTS: The general morphology of the AOB indicates that it comprises a thick glomerular layer and a thinner internal layer containing mitral/tufted, granular, and glial cells. The mitral/tufted cells have large pale-staining nuclei with intensely staining nucleoli. There does not appear to be a clearly defined granular layer. No reactivity with antibodies to neuron-specific enolase or to neurofilaments was observed in any part of the AOB, but there was some reactivity with an antibody to glial fibrillary acidic protein and widespread reactivity with an antibody to synaptophysin. CONCLUSIONS: The stratification of the AOB is simpler and less well defined than that of the main olfactory bulb (MOB), unlike in rodents in which the structure of the AOB corresponds closely to that of the MOB. According to the scale of Frahm and Bhatnagar (1980. J. Anat., 130: 349-365) the AOB of the adult dog has an intermediate position. PMID- 7992896 TI - Functional allometry of the semicircular ducts in subterranean mole-rats Cryptomys (Bathyergidae, Rodentia). AB - BACKGROUND: Since the spatial mobility of subterranean mole-rats is restricted and their skull strongly modified, morpho-functional regression of their vestibular organ may be expected. On the other hand, vestibular sense may be indispensable for orientation in a world deprived of most external sensory cues. Since vestibular sensitivity is determined by the size of the labyrinth, morphometrical analysis may be employed to assess the sensitivity and to test whether the organ is degenerate or progressively specialized. METHODS: We analyzed the shape and size of the membranous labyrinth of vestibular organs in toto in three species of African subterranean blind mole-rats of the genus Cryptomys (Bathyergidae) differing in body size yet not in habitats, ways of life, or employed orientation and locomotory strategies. The mechanical sensitivity of the cupula was estimated according to Oman et al. (1987. Acta Otolaryngol. (Stockh.), 103:1-13) for each of the three semicircular ducts. RESULTS: The size and shape of the vestibular organ changed predictably depending on species-specific (yet not individual) body mass. In some aspects, particularly the cross-sectional area, the ducts were larger than expected for a mammal of a comparable body size. In all species examined, the anterior semicircular ducts exhibited the highest sensitivity. CONCLUSIONS: The vestibular organs of blind subterranean mole-rats are not regressed morpho-functionally. PMID- 7992897 TI - Beyond CK-MB. Biochemical markers for perioperative myocardial infarction. AB - Diagnosis of perioperative myocardial infarction remains an important but challenging task. Both clinical symptoms and electrocardiographic changes have inherent limitations. Therefore, biochemical markers for myocardial injury are critical diagnostic tools. The use of creatine kinase isoenzymes (CK-MB) has enhanced detection of perioperative myocardial infarction; however, skeletal muscle damage during surgery limits CK-MB specificity. In this regard, the cardiac troponins appear to offer increased sensitivity, primarily because of their prolonged diagnostic window and even may offer enhanced specificity (especially troponin-I) in patients with surgical skeletal muscle damage. In addition, the convenience of relatively infrequent sampling (because of the prolonged diagnostic window), as well as potential cost savings, make use of the troponin markers attractive. However, definitive data in high-risk patients undergoing either cardiac or noncardiac surgery are still lacking, and significant questions remain regarding appropriate thresholds, specificity of troponin-T, and comparative accuracy of troponin-T, troponin-I, and CK-MB for diagnosis (and prognosis) of perioperative myocardial infarction. PMID- 7992898 TI - Perioperative ulnar neuropathy: are we ready for shortcuts? PMID- 7992899 TI - Preoperative myocardial cell damage in patients with unstable angina undergoing coronary artery bypass graft surgery. AB - BACKGROUND: Troponin-T is one of the contractile proteins of the myocardium. Its release into the circulation indicates various degrees of myocardial cell damage. Troponin-T may be measured in serum with a recently developed enzyme immunoassay. This immunoassay was used to evaluate the preoperative myocardial cell damage in patients with stable and unstable angina undergoing elective coronary artery bypass graft surgery, and it was compared with conventional assays of creatine kinase (CK) MB isoenzyme activity and mass. METHODS: Twenty-one patients with unstable angina and 31 with stable angina were studied. Troponin-T, CK-MB activity, and CK-MB mass were measured 24 h before anesthesia and surgery, immediately before induction of anesthesia, before and after cardiopulmonary bypass, at the end of surgery, and 24 h afterward. RESULTS: In 90% (19 of 21) of the patients with unstable angina, troponin-T was increased 24 h before anesthesia (median 0.33 microgram/l, range 0.15-5.2 micrograms/l), whereas only 3% (1 of 31) of the patients with stable angina had increased values (median 0.0 microgram/l, range 0.0-0.53 microgram/l). The difference was statistically significant (P < 0.001). The same profile was found in patients with and without unstable angina immediately before induction of anesthesia (86% [18 of 21] and 0%, respectively) and before cardiopulmonary bypass (62% [13 of 21] and 0%, respectively). In contrast to troponin-T, CK-MB activity was increased in only 0 14% of patients with unstable angina, and CK-MB mass was increased in only 9-24%. After bypass troponin-T increased in both groups (P < 0.01), but there was no longer a statistically significant difference between the groups. Twelve percent (4 of 31) of the patients in the stable angina group and 28% (6 of 21) in the unstable group had major cardiac events (P not significant). CONCLUSIONS: The study data suggest that many patients with unstable angina undergoing elective coronary artery bypass graft surgery have already increased troponin-T levels preoperatively, although conventional biochemical markers such as CK-MB activity and mass are at a normal range. Increased troponin-T and normal CK-MB concentrations may reflect some degree of ischemic myocardial cell damage. Because of the small number of patients in the study, the influence of preoperative myocardial injury on perioperative outcome could not be clarified. PMID- 7992900 TI - Ulnar neuropathy. Incidence, outcome, and risk factors in sedated or anesthetized patients. AB - BACKGROUND: Ulnar neuropathy is well-recognized as a potential complication of procedures performed on anesthetized patients. However, reported outcomes and risk factors for this problem are based on small series and anecdotes. METHODS: We retrospectively reviewed the perioperative courses of 1,129,692 consecutive patients who underwent diagnostic and noncardiac surgical procedures with concurrent anesthetic management at the Mayo Clinic from 1957 through 1991 (inclusive). The medical diagnoses of patients who had these procedures were scanned for 26 diagnoses associated with neuropathy. Persistent neuropathy of an ulnar nerve was defined as a sensory or motor deficit of greater than 3 months' duration. Risk factors anecdotally associated with persistent neuropathy were analyzed by comparing patients with an ulnar neuropathy with control subjects in a 1:3 case-control study. RESULTS: Persistent ulnar neuropathies were identified in 414 patients, a rate of 1 per 2,729 patients. Of these, 38 (9%) patients had bilateral neuropathies. Approximately equal numbers of the neuropathies included sensory loss only or mixed sensory and motor loss. Initial symptoms form most neuropathies were noted more than 24 h after the procedure. Factors associated with persistent ulnar neuropathy included male gender and a duration of hospitalization of more than 14 days (P < 0.01). Neuropathy was more likely to develop in very thin and obese patients than in patients with average body habitus. Neither the type of anesthetic technique nor the patient position was found to be associated with this neuropathy. Of the 382 patients who survived the 1st postoperative yr, 53% regained complete motor function and sensation and were asymptomatic. Of those with neuropathies persisting for more than 1 yr, most had moderate or greater disability from pain or weakness. CONCLUSIONS: These data suggest that perioperative ulnar neuropathies are associated with factors other than general anesthesia and intraoperative positioning. Men at the extremes of body habitus who have prolonged hospitalizations are particularly susceptible to development of ulnar neuropathies. PMID- 7992901 TI - Clonidine and lidocaine inhibition of isoflurane-induced tachycardia in humans. AB - BACKGROUND: A rapid increase in isoflurane concentration can induce tachycardia and hypertension and increase plasma catecholamine concentrations. To investigate a possible mechanism, we measured hemodynamic responses to isoflurane administered via mask; we also administered clonidine for premedication, lidocaine topically to the nasal mucosa, or lidocaine intravenously to evaluate the effect of these drugs on the hemodynamic responses. METHODS: Forty ASA physical status 1 patients (aged 20-30 yr) scheduled for elective oral surgery participated in the study. Thirty patients were randomly allocated to one of three groups: a control group, a group receiving 3-4 micrograms.kg-1 of oral clonidine for premedication, and a group receiving 2 ml of 4% lidocaine spray to the nasal mucosa. Ten patients were assigned nonrandomly to a group receiving intravenous lidocaine continuously (0.4 mg.kg-1 bolus followed by 30 micrograms.kg-1.min-1) after the initial randomized experiments were done to test whether systemic lidocaine blunts the responses to inhaled isoflurane. Anesthesia was induced with thiamylal, after which inhalation of 1% isoflurane in 100% oxygen via mask was begun. The inspired concentration of isoflurane was increased by 1% every 5 min to a maximum of 4%. During normocapnia and without surgical stimulation, heart rate and systolic blood pressure were measured every minute for 20 min before and during isoflurane inhalation. Plasma catecholamine concentrations were measured before and at each isoflurane concentration. RESULTS: In the control and intravenous lidocaine groups, an increase in isoflurane concentration from 2% to 3% significantly increased systolic blood pressure (peak changes of 16 +/- 5 and 15 +/- 6 mmHg, respectively) and heart rate (peak changes of 23 +/- 3 and 13 +/- 4 beats.min-1, respectively). A change in concentration to 4%, however, did not significantly alter hemodynamics. Blood pressure and heart rate responses to a change to 3% isoflurane were significantly blunted in the groups receiving clonidine (peak changes of 4 +/- 4 mmHg and 8 +/- 3 beats.min-1, respectively) or nasal lidocaine (peak changes of 2 +/- 1 mmHg and 4 +/- 2 beats.min-1, respectively) compared with the control group. In all groups, plasma epinephrine and norepinephrine concentrations increased after administration of 2% and 1% isoflurane, respectively. Plasma lidocaine concentrations were 0.3-1.3 micrograms.kg-1 in the nasal lidocaine group and 0.6 1.5 micrograms.kg-1 in the intravenous lidocaine group. CONCLUSIONS: Stepwise increases in isoflurane concentration elicited hypertension and tachycardia as well as increments in plasma catecholamine concentrations during mask anesthesia. Nasal administration of lidocaine and clonidine premedication significantly blunted the circulatory responses to isoflurane. Intravenous lidocaine did not significantly weaken the responses to changes in isoflurane concentration. PMID- 7992902 TI - Fentanyl, esmolol, and clonidine blunt the transient cardiovascular stimulation induced by desflurane in humans. AB - BACKGROUND: A rapid increase in the end-tidal concentration of desflurane to greater than 1 MAC transiently increases heart rate, arterial blood pressure, and circulating epinephrine and vasopressin concentrations. We hypothesized that drugs that block sympathetic activity or decrease sympathetic outflow (an opioid, a beta-adrenergic antagonist, and an alpha 2-adrenergic agonist) would blunt these responses. METHODS: After induction of anesthesia with intravenous propofol 2 mg/kg in ten healthy male volunteers age 25 +/- 1 yr (mean +/- standard error), anesthesia was maintained with 4% end-tidal desflurane in oxygen (0.55 MAC) via an endotracheal tube for 32 min. Controlled ventilation provided normocapnia. We then increased the end-tidal desflurane concentration within 1 min to 8% (1.1 MAC) and maintained this concentration for 10 min. On separate days, five of these volunteers were similarly anesthetized except that 5 min before the increase to 8% desflurane, we administered intravenous fentanyl 1.5 micrograms/kg and on another day 4.5 micrograms/kg (dose randomly assigned). On 2 separate days, intravenous esmolol 0.75 mg/kg was given to five volunteers 1.5 min before, or clonidine 4.3 micrograms/kg by mouth to four volunteers 90 min before, the increase from 4% to 8% desflurane. RESULTS: Without pretreatment, the increase to 8% desflurane increased heart rate (from 57 +/- 2 to 118 +/- 6 beats/min at peak, mean +/- standard error) and mean arterial blood pressure (from 66 +/- 2 to 118 +/- 5 mmHg). At the time of peak hemodynamic changes (within 1-2 min of the increase in desflurane concentration), plasma epinephrine and norepinephrine concentrations increased (from 22 +/- 6 to 339 +/- 83 pg/ml and from 205 +/- 19 to 283 +/- 30 pg/ml, respectively). Fentanyl 1.5 and 4.5 micrograms/kg attenuated the heart rate increase by 61 +/- 14% and 70 +/- 7% and the mean arterial blood pressure increase by 31 +/- 16% and 46 +/- 11% but did not alter the epinephrine or norepinephrine response at the time of peak cardiovascular changes. Esmolol attenuated the heart rate response but no other response. Clonidine attenuated all responses except that of norepinephrine and also caused postanesthesia sedation. CONCLUSIONS: Fentanyl, esmolol, and clonidine blunt the transient cardiovascular response to a rapid increase in desflurane concentration. Fentanyl may be the most clinically useful of these drugs because it blunts the increase in heart rate and blood pressure, has minimal cardiovascular depressant effects, and imposes little postanesthetic sedation. PMID- 7992903 TI - Alterations in temporal patterns of heart rate variability after coronary artery bypass graft surgery. AB - BACKGROUND: Preliminary studies have indicated that autonomic nervous system dysfunction may be present in patients after cardiac surgery. The purpose of this study was to evaluate cardiac autonomic nervous system function, as assessed by analysis of heart rate variability (HRV), in adult patients undergoing uncomplicated coronary artery bypass graft surgery. METHODS: Longitudinal changes in HRV were determined perioperatively by continuous electrocardiographic monitoring in 40 adult patients undergoing elective coronary artery bypass graft surgery and were compared with HRV in two groups of control subjects: 15 patients undergoing nonthoracic major vascular surgery and 19 healthy volunteers. Exclusion criteria were diabetes, renal failure, recent or perioperative myocardial infarction, or use of inotropic drugs. HRV data during electrocardiographically documented episodes of myocardial ischemia were omitted. RESULTS: There were no differences in any measurement of preoperative HRV between groups during the day, but HRV was greater at night (12:00 AM to 5:00 AM) in volunteers than in patients in either surgical group. In the hour after induction of anesthesia (before cardiopulmonary bypass), the components of HRV were decreased compared with those in the preoperative daytime but were similar in the two surgical groups. After surgery, HRV in the group undergoing nonthoracic vascular surgery remained at about the same level as that observed after induction of anesthesia, whereas in the group undergoing coronary artery bypass graft surgery, HRV was further reduced and was approximately 40-50% less than that in the vascular surgery group (P < 0.05). In the coronary artery bypass group, the reduction in HRV compared with the preoperative daytime measurements persisted on postoperative day 5. CONCLUSIONS: HRV is reduced after uncomplicated coronary artery bypass graft surgery. Although we cannot exclude the effects of uncontrolled variables in this reduction of postoperative HRV, the observed changes in HRV did not appear to result from general anesthesia, perioperative stress responses, and other factors associated with the early postoperative period. These data are consistent with the supposition that cardiac autonomic nervous system function is impaired after cardiac surgery. PMID- 7992904 TI - Bispectral analysis of the electroencephalogram correlates with patient movement to skin incision during propofol/nitrous oxide anesthesia. AB - BACKGROUND: Bispectral analysis is a signal-processing technique that determines the harmonic and phase relations among the various frequencies in the electroencephalogram. Our purpose was to compare the accuracy of a bispectral descriptor, the bispectral index, with that of three power spectral variables (95% spectral edge, median frequency, and relative delta power) in predicting patient movement in response to skin incision during propofol-nitrous oxide anesthesia. METHODS: Forty-four adult patients scheduled for elective noncranial surgery were studied. Gold cup electroencephalographic electrodes were placed on each patient in a frontoparietal montage (Fp1, Fp2, P3, and P4) referred to Cz, and the electroencephalogram was recorded continuously and processed off-line. Conventional frequency bands were used to describe power spectrum variables. Anesthesia was induced with propofol (1.5-3.0 mg-1.kg-1) and maintained with 60% nitrous oxide in oxygen and with propofol at one of three randomized infusion rates (100, 200, or 300 micrograms.kg-1.min-1). Inadequate anesthetic depth was defined as patient movement in response to a 2-cm skin incision at the planned site of surgery. Plasma propofol concentrations were measured within 2 min after skin incision. RESULTS: Complete data were available for 38 patients, of whom 17 moved in response to skin incision. Analysis of the area under the receiver operating characteristic curves showed that only for bispectral index and drug dose group was there a significant predictive relation (area > 0.5). Furthermore, the bispectrum was significantly predictive even after stratification by dose group. CONCLUSIONS: The bispectral index of the electroencephalogram is a more accurate predictor of patient movement in response to skin incision during propofol-nitrous oxide anesthesia than are standard power spectrum parameters or plasma propofol concentrations. PMID- 7992905 TI - An intrathecal fentanyl dose-response study in lower extremity revascularization procedures. AB - BACKGROUND: Intrathecal opioids routinely are administered to surgical patients to provide prolonged postoperative analgesia. This study evaluated the dose response effects of intrathecal fentanyl in an elderly patient population undergoing lower extremity revascularization procedures. METHODS: Surgical anesthesia was induced using a continuous spinal technique. No patient received perioperative antiemetics or opioids. Postoperatively, after complete regression of spinal anesthesia, patients received via the spinal catheter either 0, 5, 10, 20, 40, or 50 micrograms fentanyl. Blood pressure, heart rate, respiratory rate, oxyhemoglobin saturation, and visual analog pain scores were recorded approximately every minute for 15 min after study drug administration. After this initial observation period, blood pressure, heart rate, respiratory rate, oxyhemoglobin saturation were recorded every 15 min for the next 2 h, then every 30 min thereafter. A verbal analog pain score, with 0 equivalent to no pain and 10 the worst pain imaginable, was obtained with each set of vital signs. The study was concluded when the verbal analog pain score was > or = 3, the patient was medicated, and the time was recorded. Any side effects, such as respiratory depression, nausea, vomiting, and pruritus, were recorded. RESULTS: Minimal analgesia was derived from the 0-, 5-, and 10-micrograms doses. Beginning at 20 micrograms, patients experienced the onset of satisfactory analgesia (visual analog pain scores < 3) within 4 min. All patients in the 40- and 50-micrograms groups had excellent analgesia (visual analog pain scores < 1) within 10 min. No patient experienced respiratory depression (respiratory rate < 9 breaths/min), hypoxemia (oxyhemoglobin saturation < 90%), or any hemodynamic alterations (20% change greater or less than baseline heart rate or blood pressure). In the 50 micrograms group, five of ten patients complained of pruritus. CONCLUSIONS: Results indicate that 40 micrograms intrathecal fentanyl provides satisfactory analgesia for approximately 5 h in an elderly patient population, with a low incidence of side effects. PMID- 7992906 TI - Postdural puncture headache and spinal needle design. Metaanalyses. AB - BACKGROUND: Attempts have been made to reduce the incidence of postdural puncture headache (PDPH) after spinal anesthesia by changing the size and design of the needle. We wished to determine whether these strategies are effective in reducing PDPH and whether they affect the incidence of back pain and the failure rate of spinal anesthesia. METHODS: The literature was searched for trials comparing noncutting spinal needles with cutting needles and larger spinal needles with smaller needles. Trials were included if they were randomized or blinded and if outcomes included PDPH, backache, or failure of the method. The pooled odds ratio for each side effect was computed, and the results were considered statistically significant if the 95% confidence interval excluded 1. RESULTS: Four hundred fifty articles were identified by title using computerized search strategies. Thirty-one abstracts, 25 correspondences, 44 original articles, and 12 reviews were assessed. There was a reduction in the incidence of PDPH when noncutting spinal needles rather than cutting needles were used (P < 0.05), unless the discrepancy in needle size was very large. There also was a reduction in PDPH when a small spinal needle was used compared with a large needle of the same type (P < 0.05). There was no difference in the incidence of failure of spinal anesthesia or the incidence of back pain. CONCLUSIONS: We conclude that a noncutting needle should be used for patients at high risk for PDPH, and the smallest gauge needle available should be used for all patients. PMID- 7992907 TI - Hemodynamic response to induction and intubation. Propofol/fentanyl interaction. AB - BACKGROUND: When given as an intravenous bolus for induction of anesthesia, propofol can decrease postintubation hypertension but can also create moderate to severe postinduction, preintubation hypotension. The addition of fentanyl usually decreases the postintubation hypertension but can increase the propofol-induced preintubation hypotension. The goal of the study was to determine the relation between propofol and fentanyl doses and the hemodynamic changes post-induction, preintubation and postintubation. METHODS: Twelve groups of 10 patients, ASA physical status 1 or 2, first received fentanyl 0, 2, or 4 micrograms.kg-1 and then 5 min later received propofol 2.0, 2.5, 3.0, or 3.5 mg.kg-1 as an intravenous bolus for induction of anesthesia. Arterial blood pressure was continuously monitored. The trachea was intubated 4 min after propofol administration. RESULTS: The mean decrease in systolic blood pressure after propofol was 28 mmHg when no fentanyl was given, 53 mmHg after 2 microgram.kg-1 of fentanyl (P < 0.05 vs. no fentanyl), and 50 mmHg after 4 micrograms.kg-1 (P < 0.05 vs. no fentanyl; no statistically significant difference 4 vs. 2 micrograms.kg-1). There was no statistically significant difference in hemodynamic response to intubation relative to propofol dose. Hemodynamic response to intubation was decreased by the administration of fentanyl; the mean increase of systolic blood pressure after intubation was 65 mmHg from preintubation value without fentanyl, 50 mmHg after 2 micrograms.kg-1, and 37 mmHg after 4 micrograms.kg-1 (P < 0.05 for 2 and 4 micrograms.kg-1 vs. no fentanyl and for 4 vs. 2 micrograms.kg-1). Hemodynamic changes postintubation were not statistically different with increasing doses of propofol. CONCLUSIONS: Hemodynamic changes after induction with propofol or propofol/fentanyl, pre- or postintubation, are not modified when the propofol dose is increased from 2 to 3.5 mg.kg-1. Maximal hypotension preintubation occurs with a fentanyl dose of 2 micrograms.kg-1, whereas the magnitude of postintubation hypertension is significantly decreased with an increase in the fentanyl dose to 4 micrograms.kg 1. PMID- 7992908 TI - Antagonism of mivacurium-induced neuromuscular blockade in humans. Edrophonium dose requirements at threshold train-of-four count of 4. AB - BACKGROUND: Mivacurium's rapid rate of recovery has led to the suggestion that routine reversal of its residual effects may be unnecessary once signs of spontaneous recovery are evident. When antagonism is attempted at 90% twitch depression, the time saved to return to train-of-four (TOF) ratios > 0.70 compared to control has been reported to average < or = 8 min. This study was an attempt to determine whether similar savings in time could be achieved once spontaneous recovery was well underway. Also investigated was the ability of a TOF count of 4 to serve as a marker that might predict the dose of edrophonium necessary for satisfactory antagonism of mivacurium. METHODS: Fifty-eight adult patients were studied under nitrous oxide/propofol/opioid anesthesia. Neuromuscular block was monitored electromyographically and maintained by infusion of mivacurium at a level sufficient to abolish any palpable response of the thumb. TOF stimuli were delivered to the ulnar nerve at the wrist every 20 s throughout the period of observation. When the infusion was terminated, an observer was asked to note the time when the 1st through the 4th twitches first became detectable. In group 1, recovery to a TOF ratio > 0.90 was allowed to proceed spontaneously. In groups 2, 3, and 4, 0.3, 0.5, and 0.75 mg/kg edrophonium, respectively, was administered when the 4th response to TOF stimulation first became palpable. Times to TOF ratios of 0.70 and 0.90 were recorded in all groups. RESULTS: TOF counts of 1, 2, 3, and 4 first became palpable at 8 +/- 4% (SD), 20 +/- 6%, 33 +/- 9%, and 44 +/- 10% of control twitch height. Fade on TOF stimulation could no longer be detected once the TOF ratio exceeded a value of 0.41 +/- 0.07 (range 0.25-0.51). Once the 1st evoked response was palpable, the 2nd, 3rd, and 4th responses could be detected 2.5 +/- 1.1 (SD), 4.6 +/- 1.6, and 6.1 +/- 1.6 min later. Spontaneous recovery to TOF fade ratios of 0.7 and 0.9 occurred on average 10.7 +/- 2.3 and 16.9 +/- 4.7 min, respectively, after a threshold count of 4. Administration of 0.3 mg/kg edrophonium shortened the recovery process by about 7.5 min. Increasing the dose of edrophonium beyond 0.3 mg/kg did not further accelerate recovery. CONCLUSIONS: After recovery from profound mivacurium-induced neuromuscular block, TOF counts of 1, 2, 3, and 4 approximate 10%, 20%, 30%, and 40% return to control twitch height, respectively. Finally, > or = 0.3 mg/kg edrophonium will accelerate recovery from mivacurium by approximately 7-8 min. PMID- 7992909 TI - Flow velocity measurements as an index of cerebral blood flow. Validity of transcranial Doppler sonographic monitoring during cardiac surgery. AB - BACKGROUND: Transcranial Doppler sonography is increasingly used to monitor changes in cerebral perfusion intraoperatively. However, little information is available about the validity of velocity measurements as an index of cerebral blood flow (CBF). The purpose of this study was to compare invasive and Doppler derived measurements of cerebral hemodynamic variables during coronary artery bypass graft surgery. METHODS: In 15 male patients, measurements of CBF and middle cerebral artery flow velocity (VMCA) were performed before and after induction of fentanyl-midazolam anesthesia, during hypothermic cardiopulmonary bypass (CPB), and at the end of the surgical procedure. Transcranial Doppler sonography recordings of systolic, diastolic, and mean VMCA, and derived parameters such as pulsatility (PI) and resistance (RI) indexes were recorded from the proximal segment of the right middle cerebral artery. CBF was measured by the Kety-Schmidt inert gas saturation method with argon as a tracer. To facilitate comparisons of CBF and VMCA measurements, changes between consecutive measurements were expressed as percentage values. Calculations of cerebral perfusion pressure and cerebral vascular resistance (CVR) were based on jugular bulb pressure. The cerebral metabolic rate for oxygen was calculated from CBF and the arterial-cerebral venous oxygen content difference. RESULTS: Changes in mean VMCA paralleled changes in mean CBF except for hemodynamic changes associated with hypothermic CPB. At this stage of surgery, mean VMCA increased while actual CBF decreased. Separate analysis of the periods before and after CPB revealed a poor association between percentage changes in CBF and VMCA (r = 0.26, P = 0.36; r = 0.51, P = 0.06, respectively). Mean values of CVR, PI, and RI showed consistent changes after induction of anesthesia. After termination of CPB, mean CVR significantly decreased, whereas mean PI and RI remained virtually unchanged. Neither before nor after CPB was a clinically useful correlation found between percentage changes in PI, RI, and CVR (PI r = 0.28, P = 0.34; r = -0.47, P = 0.09, respectively; RI r = 0.16, P = 0.59; r = -0.53, P = 0.06, respectively). CONCLUSIONS: Hypothermic CPB seems to alter the relation between global CBF and flow velocity in basal cerebral arteries. Inconsistency in directional changes in CBF and VMCA at this stage of surgery might be attributable to changes in middle cerebral artery diameter, red blood cell velocity spectra, and regional flow distribution. Although changes in mean VMCA before and after CPB appear to parallel changes in mean CBF, individual responses of VMCA cannot reliably predict percentage changes in CBF. Furthermore, Doppler sonographic PI and RI cannot provide an approximation of changes in CVR during cardiac surgery. PMID- 7992910 TI - Thermoregulatory and anesthetic-induced alterations in the differences among femoral, radial, and oscillometric blood pressures. AB - BACKGROUND: A decrease in radial artery blood pressure relative to central arterial blood pressure is commonly associated with the rewarming phase of cardiopulmonary bypass. Decreased hand vascular resistance has been suggested as a possible mechanism. Although decreased blood viscosity due to hemodilution may contribute to decreased hand vascular resistance, thermoregulatory vascular responses to core hyperthermia also may be important. METHODS: Seven healthy volunteers were studied. Volunteers first were cooled until thermoregulatory vasoconstriction was evident. Next, each was warmed until intense sweating developed. After a cool-down period, general anesthesia was induced with propofol and N2O. Femoral artery pressure (a surrogate for central arterial pressure) and radial artery and oscillometric (brachial artery) pressures were compared during each of six defined thermoregulatory and anesthetic study conditions. To determine the effect of hand vascular resistance on blood pressure differences, measurements were compared before and after occlusion of hand blood flow. Upper extremity blood flow was evaluated by forearm and fingertip plethysmography and laser Doppler flowmetry. RESULTS: Forearm, fingertip, and cutaneous blood flow increased significantly during warming and were maximal during intense sweating. During thermoregulatory vasoconstriction, femoral, radial, and oscillometric mean blood pressures were similar. In contrast, radial artery mean pressure was 5 +/- 1 mmHg less than femoral artery mean pressure and 12 +/- 8 mmHg less than oscillometric mean pressure during intense sweating. Hand compression reduced these differences. The contour of the radial artery pressure waveform was dramatically altered by thermoregulatory and anesthetic conditions. Radial artery systolic pressure exceeded both femoral artery and oscillometric systolic pressures during vasoconstriction but was less than these during intense sweating. Hand compression reestablished the exaggerated radial artery systolic pressure during all study conditions. CONCLUSIONS: Thermoregulatory and anesthetic-induced alterations in upper-extremity blood flow substantially influence the relations among femoral artery, radial artery, and oscillometric blood pressure measurements. PMID- 7992911 TI - Dexmedetomidine decreases seizure threshold in a rat model of experimental generalized epilepsy. AB - BACKGROUND: Dexmedetomidine (DEX) is a highly selective alpha 2 agonist with marked sedative and analgesic properties thought to be mediated via reduction of central noradrenergic transmission. Because an anticonvulsant effect is associated with increased noradrenergic activity, we investigated the possible proconvulsant effects of DEX in an experimental model of generalized seizures. METHODS: Male rats (n = 82) were administered 0.9% saline as placebo (n = 18) or pretreatment drug(s) before initiation of an infusion of pentylenetetrazol (PTZ) at 5.5 mg.kg-1.min-1. The total dose of PTZ required to elicit electroencephalographic (EEG) and behavioral seizure activity was assessed. Blood samples were obtained 15 min after initiation of infusion (82.5 mg/kg) for determination of serum PTZ concentrations by gas chromatography. Pretreatment drug groups included DEX (20 micrograms/kg [n = 11], 100 micrograms/kg [n = 14], and 500 micrograms/kg [n = 10]); L-medetomidine (500 micrograms/kg [n = 7]); the alpha 2 antagonist atipamezole (500 micrograms/kg [n = 9]); and atipamezole (500 micrograms/kg) before DEX (100 micrograms/kg [n = 7] and 500 micrograms/kg [n = 6]). RESULTS: In control animals, PTZ 25-35 mg/kg induced EEG evidence of epileptiform activity. The mean dose to EEG epileptiform activity and clonic convulsions was 30 +/- 5.8 (SE) and 59 +/- 3.2 mg/kg, respectively. Infusion of DEX at 100 and 500 micrograms/kg resulted in a marked sedative response and reduced the EEG seizure threshold of PTZ to 18 +/- 1.5 and 7 +/- 1.8 mg/kg, respectively (P < 0.05 at both doses). The clonic convulsant threshold also was significantly decreased in both groups, to 37 +/- 3.2 and 28 +/- 2.3 mg/kg (P < 0.01 at each dose). Before clonic convulsion, a significantly greater number of motor seizure manifestations were scored in the DEX-treated animals at all three dose levels compared with the number scored in control animals. The proconvulsant action of DEX was not a result of alteration of PTZ kinetics, because serum concentrations did not differ between control and DEX-treated animals. Animals treated with L-medetomidine demonstrated more paroxysmal motor phenomena before clonic seizures than controls (P < 0.01) although the clonic seizure threshold was not altered. Atipamezole alone did not alter background EEG, nor did it affect the clonic convulsant threshold. Atipamezole did, however, block the proconvulsant behavioral action at both doses of DEX, raising clonic seizure threshold from 37 +/- 3.2 to 59 +/- 5.8 mg/kg (100 micrograms/kg DEX, P < 0.05) and from 28 +/- 2.3 to 59 +/- 6.9 mg/kg (500 micrograms/kg DEX, P < 0.01). CONCLUSIONS: DEX exerted a significant proconvulsant action in the PTZ experimental seizure model. The pharmacodynamic effect was dose-dependent and stereospecific and was blocked by the selective alpha 2-receptor antagonist atipamezole. These data are consistent with previous data demonstrating that inhibition of central noradrenergic transmission facilitates seizure expression. Further evaluation of DEX for possible clinical proconvulsant effects may be warranted. PMID- 7992912 TI - Electrophysiologic analysis of preemptive effects of spinal opioids on N-methyl-D aspartate receptor-mediated events. AB - BACKGROUND: Spinal N-methyl-D-aspartate (NMDA) receptor-mediated mechanisms may contribute to reduced opioid sensitivity in conditions of pain. The effectiveness of spinal opioids in inhibiting NMDA-mediated nociceptive events was assessed with two models. In addition, opioid dose-response curves with preemptive administration were compared with early and late postadministrations. METHODS: Dorsal horn nociceptive neuronal responses were recorded in the intact halothane anesthetized rat to acute repetitive C-fiber electrical stimulation (0.1 and 0.5 Hz) and to the peripheral injection of 5% formalin. At 0.5 Hz but not at 0.1 Hz, there was an enhanced C-fiber evoked response of dorsal horn neurons elicited by repetitive C-fiber stimulation (wind-up), which is mediated by the NMDA receptor. Formalin produced a biphasic response; the late protracted inflammatory phase was NMDA receptor-mediated. RESULTS: With 0.5-Hz stimulation a large degree of wind up was elicited; it was less sensitive to 5 micrograms morphine compared with the effect of the same dose on the residual wind-up elicited at 0.1 Hz. Preadministration and early postadministration of morphine were equieffective at inhibiting the second-phase formalin response. In contrast, administration of the fast-acting mu opioid, D-Ala-Gly-MePHe-Gly-ol, given late postadministration (during the second phase) was less effective than preadministration. Increasing the dose of D-Ala-Gly-MePHe-Gly-ol produced complete inhibitions. CONCLUSIONS: NMDA receptor-mediated neuronal responses, such as wind-up and the established second phase of the formalin response, are poorly responsive to opioids. Dose increases and preemptive opioids effectively inhibit these NMDA receptor-mediated events. PMID- 7992913 TI - Isoflurane inhibits hypoxic pulmonary vasoconstriction. An in vivo fluorescence microscopic study in rabbits. AB - BACKGROUND: Contradictory results have been reported in previous studies investigating the effect of isoflurane on hypoxic pulmonary vasoconstriction by indirect approaches. The current study measured the effects of one-lung ventilation (1LV) and isoflurane 1.5% by direct visual observation of the pulmonary microcirculation. METHODS: Ten New Zealand White rabbits were anesthetized with intravenous thiopental, alpha-chloralose, and piritramid. Arterial, central venous, pulmonary arterial, left atrial, and airway pressures and cardiac output were recorded continuously. 1LV was facilitated by a bronchial blocker in the right main bronchus. A transparent window was implanted into the right thoracic wall for videofluorescence microscopy of the subpleural pulmonary microcirculation. After intravenous injection of fluorescein isothiocyanate labeled red blood cells, vessel diameters, red blood cell flux, red blood cell velocity, and dynamic microhematocrit were measured in pulmonary arterioles and venules during two-lung ventilation and 1LV during baseline anesthesia and with supplementary isoflurane 1.5%. RESULTS: During intravenous anesthesia, 1LV caused significant reduction of vessel diameters and red cell flux and velocity and an increase in microvascular hematocrit in pulmonary arterioles and venules. The decreases in arteriolar diameters and red blood cell flux and velocity induced by 1LV were significantly attenuated by isoflurane as compared with those measured during baseline anesthesia (P = 0.010, P = 0.029 and P = 0.047). Accordingly, 1LV induced reduction of venular red cell flux (P = 0.023) and velocity (P = 0.036) were less pronounced during isoflurane. Isoflurane caused a significant decrease in arterial pressure. Venous admixture increased and arterial oxygen tension decreased significantly during 1LV; the changes were more pronounced during 1LV with isoflurane 1.5% than during 1LV with baseline anesthesia. CONCLUSIONS: 1LV leads to a marked reduction of microvascular diameters and blood flow in the hypoxic lung. Isoflurane 1.5% inhibits hypoxic pulmonary vasoconstriction in pulmonary arterioles and increases regional blood flow in the hypoxic lung. PMID- 7992914 TI - Hyperventilation in the treatment of metabolic acidosis does not adversely affect pulmonary gas exchange. AB - BACKGROUND: Hyperventilation has been recommended to increase blood pH during metabolic acidosis. However, hypocapnia may adversely affect arterial blood oxygenation, especially in the presence of lung disease. We therefore studied the effects of metabolic acidosis, with and without normalization of pH by hyperventilation, on pulmonary gas exchange in dogs with permeability pulmonary edema. METHODS: Six pentobarbital-anesthetized dogs were administered 0.06 ml/kg of oleic acid at least 150 min before study. Ventilation was set with an inspired O2 fraction of 0.90 and a tidal volume of 18 ml/kg, and the respiratory rate was adjusted to alter the arterial CO2 tension (PaCO2) per the experimental protocol. The protocol in random order was (1) normal pH (7.36 +/- 0.01)/normal PaCO2 (39 +/- 1 mmHg); (2) low pH 7.20 +/- 0.01)/normal PaCO2 (40 +/- 1 mmHg); (3) low pH (7.18 +/- 0.01)/hyperventilation with inspired CO2 (PaCO2 = 40 +/- 1 mmHg); and (4) normal pH (7.35 +/- 0.01)/hyperventilation with low PaCO2 (24 +/- 1 mmHg). In phases 2-4, the pH was slowly reduced by intravenous infusion of 2 N hydrochloric acid. The pH was normalized in phase 1 where necessary by infusion of sodium bicarbonate. The pH in phase 4 was normalized by reducing the PaCO2 by increasing the respiratory rate. Gas exchange was assessed by the multiple inert-gas elimination technique. RESULTS: The hemodynamic measurements remained constant throughout the protocol. Arterial O2 tension increased from 244 +/- 55 to 293 +/- 49 mmHg in the presence of metabolic acidosis (P < 0.05). Hyperventilation to normalize the pH during metabolic acidosis (phase 4), increased arterial O2 tension (313 +/- 44 mmHg, P < 0.05), and reduced shunt (from 20 +/- 5% to 12 +/- 3%, P < 0.05) compared with normal acid-base conditions (phase 1). No change in shunt was observed with hyperventilation compared with metabolic acidosis alone (phase 2). The decrease in pulmonary shunt was not attributable to the direct effects of hyperventilation, because shunt was increased (20 +/- 5%) when PaCO2 was normalized during hyperventilation by inspiration of CO2 (phase 3). CONCLUSIONS: Hyperventilation to normalize blood pH during hydrochloric acid induced metabolic acidosis did not adversely affect pulmonary gas exchange in dogs with permeability pulmonary edema. PMID- 7992915 TI - Epidural anesthesia modifies the cardiovascular response to marked hypercapnia in dogs. AB - BACKGROUND: There is little information on the cardiovascular response to marked hypercapnia during epidural anesthesia (EA). Our objective was to assess the potential modifying effects of various levels of EA on this response. METHODS: We randomly assigned 48 mongrel dogs anesthetized with halothane (0.5%) to one of four groups: control (n = 12), receiving general anesthesia alone; lumbar (n = 12), also receiving lumbar EA; thoracic (n = 12), also receiving thoracic EA; and thoracolumbar (n = 12), also receiving thoracolumbar EA. During marked hypercapnia (mean arterial CO2 tension > 90 mmHg for 15 min), we measured hemodynamic parameters and plasma catecholamine concentrations in each group. RESULTS: In the control condition, marked hypercapnia increased cardiac output, reduced systemic vascular resistance, modestly increased mean arterial blood pressure. Lumbar EA abolished the increase in cardiac output, and thoracic and thoracolumbar EA caused CO2 to depress the cardiac output and the mean arterial blood pressure during marked hypercapnia. The physiologic increase in circulating catecholamines during marked hypercapnia was abolished only in the thoracolumbar EA group. CONCLUSIONS: We conclude that sympathetic blockade by EA modifies the cardiovascular response to marked hypercapnia in dogs. Although modest hypoventilation is often effective in treating hypotension during general anesthesia, the current results suggest that hypoventilation may be detrimental during the combination of EA and general anesthesia. PMID- 7992916 TI - Effects of isoflurane and hypothermia on glutamate receptor-mediated calcium influx in brain slices. AB - BACKGROUND: To understand how volatile anesthetics protect neurons during cerebral ischemia, we studied the effects of isoflurane on cerebral glutamate receptor-mediated calcium influx. Calcium influx via these key excitatory receptors may mediate pain transmission, memory, and the pathophysiologic sequelae of cerebral anoxia or ischemia. Because cerebral protection by hypothermia may involve a decrease in glutamate receptor activity, we also examined the interaction of temperature and isoflurane on glutamate receptor inhibition. METHODS: We measured glutamate receptor-mediated changes in cytosolic calcium in 300-microns-thick rat cortical brain slices. Temperature was varied to 28, 34, 37, or 39 degrees C and isoflurane partial pressure to 0.016-0.019 atm (equivalent to 1.16 minimum alveolar concentration [MAC], adjusted for temperature and age). Brain slices were loaded with fura-2 to permit measurement of cytosolic free calcium. Calcium changes due to the glutamate receptor agonist N-methyl-D-aspartate (NMDA) (50 microM), to ischemia levels of L-glutamate (1.0 mM) or to simulated ischemia (1.0 mM glutamate, 100 microM NaCN, and 3.5 mM iodoacetate) was then measured. Slice lactate dehydrogenase leakage and adenosine triphosphate were measured as indices of cellular integrity. RESULTS: Isoflurane reduced both L-glutamate and NMDA-mediated calcium fluxes by approximately 60%. Neither the activity of the NMDA receptor nor its inhibition by isoflurane was altered by temperature. The rate of calcium influx during ischemia was significantly reduced both by temperature and by isoflurane (P < 0.05). Adenosine triphosphate loss and lactate dehydrogenase leakage were reduced by isoflurane during simulated ischemia by 37% and 73% (P < 0.05), respectively. CONCLUSIONS: (1) At 1.16 MAC, isoflurane potently inhibits glutamate receptors and delays cellular injury induced by simulated ischemia, and (2) hypothermia does not reduce the intrinsic activity of cortical glutamate receptors but delays calcium accumulation during simulated ischemia. Isoflurane reduces the severity of key pathophysiologic events in an in vitro model of simulated cerebral ischemia. PMID- 7992917 TI - Dose-dependent effects of halothane on the carbon dioxide responses of expiratory and inspiratory bulbospinal neurons and the phrenic nerve activities in dogs. AB - BACKGROUND: Expiratory bulbospinal and inspiratory bulbospinal neurons in the ventral respiratory group provide drive for thoracoabdominal expiratory and phrenic and thoracic inspiratory motor neurons. Potent inhalational agents such as halothane may have differential effects on inspiratory and expiratory neurons, but detailed studies comparing neurons at a homologous level are lacking. METHODS: The dose-dependent effects of anesthesia with 1.0-2.5 minimum alveolar concentration halothane on the CO2 responses of single expiratory and inspiratory bulbospinal neurons of the ventral respiratory group and on phrenic neural activities were studied in nonpremedicated, anesthetized, paralyzed, vagotomized dogs. Hyperventilation with O2 and the addition of CO2-O2 mixtures were used to produce low, medium, and high steady-state levels of central CO2 drive. RESULTS: Peak neuron discharge frequency decreased progressively with increasing halothane dose at all levels of CO2 drive for both types of neurons. The sensitivities of inspiratory and expiratory bulbospinal neuronal activities to halothane were not significantly different from one another, whereas the sensitivity to halothane of the peak phrenic activity was markedly greater than those of the neurons. Increasing halothane dose caused a downward, predominantly parallel shift of the CO2 response curves. Phrenic nerve activity also showed a decrease in slope of the CO2 response. CONCLUSIONS: The activities of respiratory premotor neurons are less depressed by increasing doses of halothane than is phrenic nerve activity. The greater depression of phrenic activity may result from additional anesthetic actions on the efferent motor pathways, resulting in decreased descending synaptic inputs to phrenic motor neurons. PMID- 7992918 TI - Anesthetic depression of spinal motor neurons may contribute to lack of movement in response to noxious stimuli. AB - BACKGROUND: Previous studies suggest that anesthetics produce immobility by an action on the spinal cord. We postulated that immobility results from a depression of alpha-motor neuron excitability in vivo, and that this depression would be reflected in a depression of recurrent, (F)-wave activity. METHODS: The lungs of 15 normocapnic, normothermic, normotensive rats were mechanically ventilated with 0.5, 0.8, 1.2, and 1.6 MAC isoflurane, in random sequence, with at least 30 min of equilibration at each step. In addition, at 1.2 MAC, inspired carbon dioxide was altered to create hypercapnia and hypocapnia. The sizes of the orthodromic (M) wave and F wave were measured in ten sequential trials as the activity in the intrinsic muscles of the ipsilateral foot evoked by stimulation of the tibial nerve. RESULTS: M-wave amplitude did not change. F-wave amplitude did not decrease between 0.5 and 0.8 MAC but decreased 50% between 0.8 and 1.2 MAC (P < 0.001) and 60% between 1.2 and 1.6 MAC (P < 0.05). Hypocapnia (17 mmHg) increased F-wave amplitude by 15%, and hypercapnia (73 mmHg) reduced it by 60% compared with normocapnia at 1.2 MAC (31 mmHg) (P < 0.0001). CONCLUSIONS: Anesthetics may cause and moderate hypercapnia may contribute to surgical immobility by depressing excitability of alpha-motor neurons. Monitoring F waves may indicate the adequacy of this aspect of anesthesia and may detect states in which spontaneous or nocifensive movements might occur. PMID- 7992919 TI - Intrathecal magnesium sulfate protects the spinal cord from ischemic injury during thoracic aortic cross-clamping. AB - BACKGROUND: Paraplegia is a known complication after surgery on the descending thoracic aorta. Thoracic aortic cross-clamping causes an increase in proximal aortic and cerebrospinal fluid pressures. Sodium nitroprusside, though effectively decreasing proximal aortic pressure, has been implicated in worsening the incidence of paraplegia by further increasing cerebrospinal fluid pressure and decreasing distal blood pressure, thereby reducing spinal cord perfusion pressure. Intravenous administration of magnesium sulfate has been shown to offer some spinal cord protection when used with mild hypothermia. This study investigated the effect of intrathecal magnesium on the prevention of paraplegia when sodium nitroprusside is used to control proximal hypertension during thoracic aortic cross-clamping in a dog model of spinal cord ischemia. METHODS: Two groups of eight dogs underwent thoracic aortic cross-clamping via a small thoracotomy incision for 45 min. Proximal, distal, and central venous pressures and cerebrospinal fluid pressures were monitored. Temperature was maintained at 36 degrees C. Sodium nitroprusside was used to control proximal hypertension. The control group received no magnesium sulfate, and a second group received 3 mg/kg intrathecal magnesium sulfate before thoracic aortic cross-clamping. The dogs were neurologically evaluated 24 h later by an observer blinded to the dogs' group. Spinal cord segments were obtained for histologic examination. RESULTS: Proximal mean arterial pressure, cerebrospinal fluid pressure, spinal cord perfusion pressure, and central venous pressure were not statistically different between the two groups. Neurologic outcome, however, was statistically different between the groups. None of the eight dogs in the magnesium group had any measurable neurologic injury, in contrast to the control group, in which seven of the eight dogs had severe neurologic injury (P < 0.005). Post mortem histologic data supported these findings. CONCLUSIONS: Intrathecal magnesium can prevent spinal cord injury despite markedly negative spinal cord perfusion pressure during thoracic aortic cross-clamping in a canine model of spinal cord ischemia. PMID- 7992920 TI - Does the brain influence somatic responses to noxious stimuli during isoflurane anesthesia? AB - BACKGROUND: Recent evidence suggests that anesthetic action within the spinal cord is important in suppressing somatic responses to painful stimuli. Whether the brain influences this response is not clear. This study was designed to test the hypothesis that the brain affects anesthetic requirements. METHODS: Six goats were anesthetized with isoflurane. After tracheal intubation and femoral arterial cannulation, bilateral neck dissections were performed to isolate the external carotid arteries and external jugular veins. The occipital arteries were ligated bilaterally. Control isoflurane requirements as defined by the minimum alveolar concentration (MAC) were determined by using a dew-claw clamp as a painful stimulus. Cranial venous blood was drained into a bubble oxygenator in which an isoflurane vaporizer was placed in line with the gas flow, and arterial blood was infused into a carotid artery with a roller pump. This arrangement permitted selective control of the delivery of anesthetic to the head and to the systemic circulation. Isoflurane concentration in the arterial blood delivered to the head was estimated from the isoflurane concentration in the oxygenator exhaust. While isoflurane concentration in the head was maintained at approximately 0.2-0.3%, MAC for the body was determined. After return to the native circulation, MAC was determined again. RESULTS: During bypass with cranial isoflurane concentration at 0.2-0.3%, all animals showed varying, intermittent degrees of light anesthesia, including spontaneous head movement, chewing, swallowing, and eye opening. Isoflurane MAC was 1.4 +/- 0.2% (mean +/- SD) at baseline, decreased to 0.8 +/- 0.1% during bypass (P < 0.05), and increased to 1.2 +/- 0.2% after bypass (P not significant compared with baseline). CONCLUSIONS: These results verify the importance of volatile anesthetic action at an extracranial site vis a vis purposeful movement in response to a noxious stimulus. Furthermore, the results confirm that the brain affects anesthetic requirements. PMID- 7992921 TI - Metabolism of glucose, glycogen, and high-energy phosphates during complete cerebral ischemia. A comparison of normoglycemic, chronically hyperglycemic diabetic, and acutely hyperglycemic nondiabetic rats. AB - BACKGROUND: Increases in brain glucose will worsen outcome after global cerebral ischemia, and some experimental evidence suggests that the duration of hyperglycemia also may influence outcome. Different types of hyperglycemia were studied to identify metabolic differences that might account for alterations in postischemic outcome. METHODS: Ninety pentobarbital-anesthetized Sprague-Dawley rats were divided into three groups: normoglycemic nondiabetic rats (N) (n = 30), chronically hyperglycemic diabetic rats (HD) (n = 30), and acutely hyperglycemic, glucose-infused nondiabetic rats (HN) (n = 30). These groups were further subdivided into groups of six rats each that received 0, 2.5, 5, 10, or 15 min of complete cerebral ischemia (potassium chloride--induced cardiac arrest). Brains were excised after 10-kW focused microwave radiation and metabolites were measured using enzymatic fluorometric techniques. RESULTS: At all study intervals, plasma glucose concentrations in HD and HN were fourfold greater than in N. Before ischemia, brain glucose concentrations in all groups were proportional to plasma glucose concentrations; however, brain glycogen concentrations did not differ among groups. After the onset of ischemia, there was an immediate diminution of brain glucose, glycogen, adenosine triphosphate (ATP), and phosphocreatine that in all cases was most pronounced during the initial 2.5 min of ischemia. Consumption of carbohydrate stores and lactate production were greater in HD and HN than in N. HD had lesser preischemic ATP concentrations and energy charges relative to N and HN (P < 0.05), perhaps reflecting their disease state; however, at 2.5 min of ischemia, the relationship of ATP concentrations and energy charges was HN > HD > N (P < 0.05 among all). In all groups, ATP and phosphocreatine were more than 96% depleted by 10 min of ischemia. With few exceptions (ATP concentrations and energy charges before ischemia and at 2.5 min, and lactate concentration in HD < HN at 15 min), there were no measured metabolic differences between HD and HN. CONCLUSIONS: In these studies, the duration of hyperglycemia did not affect intraischemic carbohydrate consumption. At short durations of ischemia (2.5 min), both HD and HN groups had greater intraischemic ATP concentrations and energy charges than N; however, at longer durations of ischemia (> 5.0 min), high-energy phosphate depletion was similarly severe in all groups. These studies suggest that energy failure is not the origin of worse postischemic neurologic injury in hyperglycemic subjects, nor does energy failure readily explain reported differences between acutely and chronically hyperglycemic subjects exposed to global cerebral ischemia. PMID- 7992922 TI - Perturbation of ion channel conductance alters the hypnotic response to the alpha 2-adrenergic agonist dexmedetomidine in the locus coeruleus of the rat. AB - BACKGROUND: The alpha 2-adrenergic agonists are members of a novel class of hypnotic-anesthetic agents that selectively bind to alpha 2 adrenoceptors in the locus coeruleus (LC) to initiate their pharmacologic action. The postreceptor molecular mechanism of the hypnotic action of alpha 2-adrenergic agonists remains unknown. In this study we addressed the role of conductance through a variety of calcium and potassium ion channels in the hypnotic action of dexmedetomidine in the LC of the rat. METHODS: Cannulas were inserted stereotactically into the LC of halothane-anesthetized rats (n = 318). After at least 48 h, rats were tested for loss of righting reflex in response to administration of the alpha 2 adrenergic agonist dexmedetomidine at a hypnotic (7.0 micrograms LC) or subhypnotic (3.5 micrograms LC) dose. To establish the mediating role of various species of calcium and potassium ion channels in the hypnotic response, rats were pretreated with the following drugs before the administration of dexmedetomidine LC:S(+)202791 (L-type calcium-channel activator), nifedipine and R(-)202791 (L type calcium-channel blocker), SNX 111 (N-type calcium-channel blocker), SNX 230 (P-type calcium-channel blocker), quinine (calcium-activated and voltage-gated potassium-channel blocker), charybdotoxin (calcium-activated potassium-channel blocker), dendrotoxin (voltage-gated potassium-channel blocker), or glybenclamide (adenosine triphosphate-sensitive potassium-channel blocker). The drugs were used in doses not causing behavioral effects that could have confounded the interpretation of loss of righting reflex. RESULTS: SNX 230 and the dihydropyridines nifedipine and R(-)202791 produced loss of righting reflex in the presence of a subhypnotic dose of dexmedetomidine. The hypnotic-enhancing effects of the dihydropyridines could be blocked with S(+)202791, which also diminished loss of righting reflex in response to dexmedetomidine 7.0 micrograms LC. Quinine, dendrotoxin, and charybdotoxin each attenuated the hypnotic response to dexmedetomidine 7.0 micrograms LC. The hypnotic response to dexmedetomidine was not significantly altered by SNX 111 or glybenclamide. CONCLUSIONS: Inhibition of ion conductance through L- or P-type calcium channels and facilitation of conductance through voltage-gated or calcium-activated potassium channels may be involved in the mechanism of hypnotic action of alpha 2 adrenergic agonists. These changes in ion conductance were capable of producing membrane hyperpolarization and decreasing neuronal excitability. There was no evidence for the involvement of adenosine triphosphate-sensitive potassium channels or N-type calcium channels in the hypnotic response to dexmedetomidine. PMID- 7992923 TI - Electrical seizures during sevoflurane anesthesia in two pediatric patients with epilepsy. PMID- 7992924 TI - Nitric oxide reduces pulmonary hypertension during hepatic transplantation. PMID- 7992925 TI - Paraplegia in a patient with an intrathecal catheter and a spinal cord stimulator. PMID- 7992926 TI - Transesophageal echocardiography confirms atelectasis due to right mainstem bronchial intubation. PMID- 7992927 TI - Sympathetically maintained pain and the use of regional anesthesia. PMID- 7992929 TI - Laryngeal mask airway-assisted, wire-guided fiberoptic tracheal intubation. PMID- 7992928 TI - Echocardiographic identification of paradoxical air embolism. PMID- 7992930 TI - Application of negative-pressure ventilation when changing endotracheal tubes. PMID- 7992931 TI - Evaluation of double lesion syndrome with diagnostic spinal anesthesia. PMID- 7992932 TI - [Respiratory effects of midazolam in patients with obstructive sleep apnea syndromes]. AB - The administration of benzodiazepines at sleeping doses can be followed by an increased rate of upper airways obstruction episodes, especially in patients with an obstructive sleep apnea syndrome (OSAS). However, the effects of benzodiazepines at premedication doses have not yet been assessed. Therefore, fourteen patients were studied after administration of midazolam 0.08 mg.kg-1 i.m.: seven with an OSAS diagnosed previously (baseline recording) (= OSAS group) and seven without risk factors for OSAS (= Control group). The recordings were undertaken in the sleep laboratory. The airflows were assessed by nasal and oral thermistors and chest and abdominal movements by strain gauges. The electromyogram of the chin muscles was recorded, the electroencephalogram and the electro-oculogram electrodes were placed as described by RECHTSCHAFFEN and KALES. The arterial saturation in oxygen (Spo2) was monitored by pulse oximetry. All the signals were digitized and fed into a computer. The apnea was defined as a cessation of airflows for a least 10 s. The hypopnea was defined as a 10 s decrease in airflow with a drop in Spo2 of 4% or more. The respiratory event (apnea or hypopnea) was qualified as obstructive if the thoraco-abdominal movements persisted. The rate and the duration of respiratory events per sleep hour (mean +/- SEM) in OSAS group after midazolam (respectively 29.6 +/- 10 and 11.2 +/- 3.5 min) were not different from those of the baseline recording (respectively 38.4 +/- 11.6 and 12 +/- 3.5 min) and were significantly higher than in the control group (respectively 38.2 +/- 2 and 1.8 +/- 1.3 12 +/- 3.5 min) and were significantly higher than in the control group (respectively 3.8 +/ 2 and 1.8 +/- 1.3 min; p < 0.05). In the OSAS group, the percentage of sleeping time spent with a Spo2 < 90% was 1.5 +/- 1.4% during the baseline recording and 4.7 +/- 1.9% after midazolam (difference n.s.). However, a dramatic increase was observed in two patients.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7992933 TI - [Comparison of amoxicillin and cefamandole in the prevention of bronchopulmonary infections in pulmonary surgery. A randomized double-blind study]. AB - Antibiotic prophylaxis is currently recommended in clean-contamined surgery (type II of Altemeier classification). Pulmonary surgery belongs to this type. This prospective randomized and controlled study was designed to compare amoxicillin and cefamandole for prevention of pleural and bronchopulmonary infections after pulmonary resections. It included 256 patients, admitted between October 1st 1989 and July 1st 1991, for elective thoracotomy and probable pulmonary resection. The patients were allocated into two groups, group A (amoxicillin) and group C (cefamandole). The first intravenous antibiotic injection took place immediately after induction of anaesthesia (1 g of amoxicillin or 1.5 g of cefamandole). Postoperative injections were performed every 6 hours during 36 hours (i.e. a total of 6 injections). Infection was defined by the association of general signs including hyperthermia (> 38 degrees C), hyperleucocytosis (> 12,000/mm3), and local signs such as bronchitis (B), pneumonia (P), empyema (E), wound sepsis (W) and non thoracic infection (S). Follow-up included the hospital stay and a period of eight months after surgery for possible rehospitalisation for infection. Respiratory infections (bronchitis n = 35, pneumonia n = 5, empyema n = 2) occurred in 18% of the total population. No difference was seen between the two groups concerning the type of infection and the repartition of infection in relation to the type of pulmonary surgery. The causative bacterial organisms were Haemophilus influenzae (n = 4), Streptococcus pneumoniae (n = 2), Escherichia coli (n = 1), anaerobic bacteria (n = 1). Multiple bacteria were found in one case. The empyema and wound sepsis occurred in the amoxicillin group.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7992934 TI - [Risk evaluation of oxygen desaturation after buprenorphine or morphine administration during the early postoperative period]. AB - The purpose of this study, conducted in a PACU in the early recovery period of orthopaedic procedures under general anaesthesia, was to compare the time course of O2 arterial saturation (SpO2), measured by pulse oximetry, after the intramuscular administration of either buprenorphine (0.30 mg) or morphine (10 mg). The rate of patients who had an episode of O2 desaturation (defined as a SpO2 under 95%) was similar in both groups: 73% after buprenorphine vs 67% after morphine. The cumulative duration of desaturation episodes was higher following buprenorphine (p < 10(-5). Finally, in patients who had at least one episode of arterial desaturation, the mean duration of these episodes was identical in both groups. However the average number of episodes per patient was significantly higher in the buprenorphine group. These results should lead us to be cautious with the use of buprenorphine during the early recovery period, especially as this as this agent has specific characteristics such as a long duration of action and resistance to naloxone. PMID- 7992935 TI - [Unrecognised intake of trace elements in polytraumatized and burnt patients]. AB - Recommended trace element doses during parenteral nutrition have been revised many times and increased, especially in surgical patients. Blood products are known to provide significant amounts of trace elements under certain circumstances. In intensive care patients crystalloids and colloids are also given in large amounts. This study aimed at determining the magnitude of the unrecognized trace element administrations after major burns and/or trauma. Fifteen patients burnt 36 +/- 11% (mean +/- SD) of body surface area, aged 34 +/- 8 years, admitted to the Burns Centre and 11 trauma patients with an Injury Severity Score of 29 +/- 6 points, aged 40 +/- 13 years, admitted to the surgical Intensive Care Unit in a Swiss University Hospital. Prospective study of intakes and urinary excretion from the first post-injury day (D1) to D7. Copper and zinc were analyzed by flame atomic absorption spectrophotometry, and selenium by fluorimetry. The actual trace element administrations were much larger than those prescribed in the 3 groups of patients, and were significantly above the most recent parenteral recommended daily allowance = RDA (2.3 times RDA for copper, 5 times for selenium and zinc in Group 2, which received the largest i.v. supplements). There greatest provision of the 3 elements was by the blood products (packed red cells and frozen plasma) and by the albumin solutions (0.5 mg.L-1 Cu, 90 micrograms.L-1 Se and 2.1 mg.L-1 Zn in the 20% solutions). During the resuscitation phase, crystalloids provided a significant amount of copper (0.14 mg.L-1 NaCl 0.9%, none in dextrose) and zinc (0.3 mg.L-1 of any crystalloid), whereas selenium was not detected.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7992936 TI - [Complications and outcome of implantable infusion pumps: apropos of 60 cases]. AB - The aim of this study was to analyse the complications and the outcome in 59 patients with 60 implantable ports for cancer chemotherapy. Perioperative complications included: subcutaneous haematoma (n = 6), wrong position of the catheter tip (n = 2), accidental intravascular injection of lidocaine with adrenaline (n = 1), vagal reflex (n = 1) and pneumothorax (n = 1). Late complications included extravasation of drugs (n = 4), wound dehiscence (n = 1), spontaneous migration of the catheter tip (n = 2), venous thrombosis (n: = 2), septicaemia (n = 6), local discomfort (n = 6) and ports' obstruction (n = 15). In 11 cases, repermeabilization was possible with heparin or streptokinase. Patients were followed up to 40 months, 37% died with a patent port, 6% died with an obstructed port and 45% are still alive with a functional port. Twelve percent of the ports were removed. The lack of life-threatening complications, the high rate of satisfied patients (85%) and the long mean period of use (11 months) in this study are similar to those published in the literature and confirm the value of implantable ports for chemotherapy. PMID- 7992937 TI - [Anaphylactoid reactions to colloid plasma substitutes: incidence, risk factors, mechanisms. A French multicenter prospective study]. AB - Changes in transfusion behaviour induce a widespread use of colloid plasma substitutes, the range of which has recently been enlarged by the marketing of starch derivatives. The product chosen depends, at least in part, on its adverse effects, anaphylactoid reactions being a part of these. This study aimed to discover the frequency and severity of these reactions according to the type of substitute available in France, to look for possible risk factors, and determine the mechanisms involved. A prospective inquiry was carried out in 49 public and private hospitals spread throughout France. It lasted for 15 months, between June 1991 and October 1992. A data sheet was filled in for each patient who was given a plasma substitute, whether or not there was an incident. When a reaction did occur, an assessment was carried out in two stages: straightaway, with the measurement of the concentrations of serum tryptase, antigelatin antibodies, urinary methylhistamine; and four to six weeks later, with skin tests. A series of 19.593 patients was thus collected: 48.1% were given gelatins, 26.7% starches, 15.7% albumin, and 9.5% dextrans. 43 anaphylactoid reactions were recorded, giving an overall frequency of 0.219%, or 1 reaction for 456 patients. The frequency differed according to the substitute considered: 0.345% for gelatins, 0.273% for dextrans, 0.099% for albumin, and 0.058% for starches. These reactions (grades III and IV) were serious in 20% of cases. Multivariate analysis revealed four independent risk factors: giving gelatins (odds ratio: 4.81), giving dextrans (odds ratio: 3.83), a history of drug allergy (odds ratio: 3.16), and being male (odds ratio: 1.98). The relative risks of anaphylactoid reactions due to one type of substitute with respect to another were estimated to be 6 times less for starches with respect to gelatins, and 4.7 times less than with dextrans. The relative risk of albumin is 3.4 times less than that of gelatins, and almost identical to that of the starches. An immuno-allergological assessment was only carried out in 15 patients who had been given a gelatin (Plasmion). IgE dependent anaphylaxis was proven in 7 of these. To conclude, it was shown that gelatins and dextrans should be avoided in patients with a known history of drug allergy. When a reaction does occur, an allergological assessment must be carried out, as this may be due to specific antibodies. Should this prove to be the case, that particular substitute would be contraindicated for the rest of the patient's life. PMID- 7992938 TI - [Efficacy and tolerance of Fraxiparine in the prevention of deep vein thrombosis in general surgery performed with medullar conduction anesthesia]. AB - From 1989 to 1991, 480 patients undergoing general surgery under epidural anaesthesia were included in a multicentre, comparative, randomized, open-study designed to assess whether calcium nadroparin (Fraxiparine), one daily subcutaneous injection of 0.3 mL, i.e. 3,075 anti Xa IU per day, is more efficiency and better tolerated than a non-fragmented standard heparin (Calciparine), one subcutaneous injection of 0.2 mL t.i.d. 15,000 IU per day, for the prevention of postoperative deep vein thrombosis (DVT). The 480 patients, treated in 78 centres, were randomized in two groups (Fraxiparine, n = 241; Calciparine, n = 239). In both groups, treatment was started two hours after the end of the surgical procedure. Hernia repair and prostatic surgery accounted for 60% of operations. Thromboembolic events were detected by clinical examination performed at regular time intervals and by a systematic exam (doppler and rheoplethysmography or ultrasonogram) at the end of the treatment. Both agents demonstrated a similar efficiency. There was only one case of DVT, confirmed by phlebography in the Fraxiparine group. Tolerance was good in both groups. The proportion of patients requiring a transfusion was low (3% in each group). Hematuria was relatively frequent (33% in the Fraxiparine group and 28% in the Calciparine group), however these rates were related to prostatic and urinary incontinence surgery. This study, including a wide series of patients undergoing general surgery under epidural anaesthesia, demonstrates that efficiency and tolerance of one daily injection of Fraxiparine are similar to those of three daily injections of Calciparine. It it concluded that Fraxiparine improves of the patient's comfort and decreases the nursing work load. PMID- 7992939 TI - [Comparison of Orth-Evac and Solcotrans Plus devices for the autotransfusion of blood drained after total knee joint arthroplasty]. AB - Surgical wound blood which is ched through drains after total knee replacement surgery with a tourniquet may be returned to the patient using special collecting devices. This study aimed to compare two systems, Orth-Evac and Solcotrans Plus an to assess the safety of the reinfusion of non washed blood cells. It included 30 patients scheduled for total knee replacement surgery, free from tumoral or coagulation disease and allocated randomly in three groups of 10 each: the Orth Evac group (OGr), the Solcotrans Plus group (SGr) and the Control group (CGr). The devices, not containing an anticoagulant, were connected to the deep suction drains in the operating room, after skin closure and before the tourniquet removal. The salvaged blood was reinfused in the subsequent six hours via a 40 microns filter. The volume of collected blood was measured and homologous blood was added as required, to maintain a hematocrit of 30%. A blood sample was obtained the day before surgery (D - 1), before reinfusion (D0), two hours later (D + 2h), one day later (D + 1), and from the collecting device before reinfusion. The statistical analysis used the Kruskal-Wallis test and Steel-Dwass procedure to confirm the difference between two groups. The three groups did not differ in age, weight, height and gender. The volume of salvaged and autotransfused blood was 925 +/- 156 mL in OGr and 605 +/- 178 mL in SGr respectively, transfusion of homologous blood was required in two patients of OGr, four of SGr and six of CGr. At D + 1, the hematocrit was comparable in all groups (OGr = 28%, SGr = 28.2% and CGr = 28.5%).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7992941 TI - [Electric infusion devices: criteria of choice and comparative analysis of 45 models available in France]. AB - This study compared 45 electric infusion devices, either constant flow pumps or syringe pumps, available in France. These devices were tested for start-up delay, time to alarm following occlusion, bolus following occlusion, accuracy of flow rate and pressure output. Ergonomic, environmental and various technical criteria such as safety in continuous perfusion, correct positioning of infusion sets, air in line and end of perfusion detection were also considered. Users can compare these devices in easy to read tables. The newest devices include systems improving the quality of flow. PMID- 7992940 TI - [Prehospital air ambulance and systemic secondary cerebral damage in severe craniocerebral injuries]. AB - Advanced supportive therapy at the site of the accident, associated with direct transfer to a trauma centre increases survival and reduces morbidity rates. Patients with severe head injury, especially those with multiple injuries, often arrive in the emergency department with potentially causes of serious secondary systemic insults to the already injured brain, such as acute anemia (Hematocrit < or = 30%), hypotension (systolic arterial pressure (Pasys) < or = 95 mmHg, 12.7 kPa), hypercapnia (Paco2 > or = 45 mmHg, 6 kPa) and/or hypoxemia (Pao2 < or = 65 mmHg, 8.7 kPa). The incidence of such insults and their impact on mortality were studied in a group of 51 consecutive adults suffering from non penetrating severe head injury (Glasgow score < or = 8, mean age 31 +/- 17 yrs) rescued by a medicalized helicopter. Each patient received medical care on the site of the accident by an anaesthesiologist of a university hospital (UH) complying with an advanced trauma life support protocol including intubation, hyperventilation with FiO2 = 1, restoration of an adequate Pasys and direct transportation to the UH. Mean delay from call to arrival of the rescue team on the site was 15 +/- 5 min. Mean scene time was 32 +/- 10 min in cases not requiring extrication. Nineteen patients (Group I) were admitted without secondary systemic insults to the brain, 13 with isolated head injury, and 6 with multiple injuries, with a low Glasgow Outcome Score (GOS 1-3) of 42% at 3 months. In 32 patients (Group II), despite advanced supportive measures at the scene of the accident and during transportation, one or more secondary systemic insults to the brain were detected upon arrival at the emergency room, one with isolated head injury, 31 with multiple injuries, with a bad GOS of 72% at 3 months. We conclude that: 1) advanced trauma life support prevents from secondary systemic insults in the great majority of isolated severe head injured patients. 2) secondary systemic insults to the already injured brain are frequent in patients with multiple injuries and are difficult to avoid despite rapid aeromedical trauma care, 3) secondary systemic insults to the brain have a catastrophic impact on the outcome of severely head injured patients. PMID- 7992942 TI - [Electric infusion devices]. AB - Electrical infusion devices are specifically aimed to maintain an accurate and constant flow rate. The infused agents can be allocated into three categories of risk, according to their therapeutical index and their infusion rate. Each category requires infusion devices with the corresponding performances. Moreover the choice of a device depends also on ergonomical and environmental criteria as the area of use (e.g. ambulatory patient, transport, neonates, intravenous anaesthesia). PMID- 7992943 TI - [Role of isotopic imaging in intensive care]. AB - The real place of isotopic imaging in intensive care patients remains still unclear. This review aimed to consider the indications of isotopic imaging for improved diagnosis and therapy and to specify its place among the other techniques of exploration. Pulmonary perfusion and ventilation scintigraphies are valuable for the diagnosis of pulmonary embolism (PE). A "high probability" scintigraphy of the lungs ascertains the diagnosis of PE and allows to start a specific treatment without requiring a pulmonary angiography. This is not the case in the presence of a history of previous PE or if the arguments for a PE are only weak. A normal lung scintigraphy eliminates the diagnosis of a clinically significant PE all the more as an exploration of good quality of the lower limb veins remains negative. In the opposite a "non diagnostic" scintigraphy justifies a pulmonary angiography in intensive care patients. The diagnosis of myocardial contusion is made uneasy as the clinical symptoms, the ECG, the cardiac enzymes and the chest X-ray are only of limited value. Isotopic explorations of the heart could provide additional valuable data or be an alternative for 2 D echocardiography. The comparison of CPK-MB concentrations with a myocardial scintigraphy using thallium 201 is given as being very reliable, with positive and negative predictive values higher than 80%. An exploration restricted to the cardiac ejection fractions is only of limited value. In the future, an improvement will perhaps be obtained with tracers such as MIBI labelled with technetium 99m, which allow the simultaneous assessment of myocardial perfusion and the ventricular ejection fractions as well. The localisation of centres of infection, especially when intra-abdominal, remains difficult in intensive care patients. Isotopic imaging, especially the scintigraphies with labelled polynuclears, could allow in combination with conventional imaging techniques (computed tomography and 2 D echocardiography) to prevent from errors in diagnosis. An array of arguments is essential for ascertaining the presence of an abscess. Scintigraphies with leucocytes labelled with indium 111 or technetium 99m are qualified as having a sensitivity and a specificity greater than 90%. The conventional techniques of measurement of the cerebral blood flow (CBF) using xenon 133 require a special equipment or are invasive. Other cerebral tracers, such as cyclic amines (HMPAO) labelled with technetium 99m and administrable by i.v. route, allow the use of a standard tomo-gamma camera, and could be of help in various pathological conditions.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 7992944 TI - [Anesthesia for MRI examination]. AB - Magnetic resonance imaging (MRI) requires the patients to stay for 30-45 min in a magnetic closed noisy space. Therefore most children and agitated adults require general anaesthesia or sedation in order to high quality images. Anaesthesia may be given by several routes (TIVA, inhalational or intrarectal administration) using common drugs. However, the magnetic field limits the selection of patients undergoing MRI and the spectrum of anaesthetic and monitoring equipment. The magnetic field may have deleterious effects on implanted ferromagnetic devices. It may attract objects towards the magnet centre at a dangerous speed. Moreover it may disturb the function of monitors and anaesthesia machines which should be tested for a specific magnetic field strength before introducing their use in a given MRI unit. PMID- 7992945 TI - [Intra-abdominal pressure]. AB - The abdominal pressure is a hydrostatic one, which can be measured in the bladder, the rectum and the stomach. In physiologic conditions, the abdominal pressure is variable, with peaks as high as 100 to 200 mmHg at the time of defecation, cough. The increase in abdominal pressure elicited by abdominal distension or compression acts directly on the abdominal compartment, indirectly on the thoracic compartment, and modifies the circulation and the ventilation. Venous return is decreased as the inferior vena cava is compressed. The systemic resistances are also increased as the abdominal vessels are compressed. Therefore the circulation is mainly distributed to the superior part of the body. Although the cardiac output is decreased, the usual haemodynamic parameters remain in the normal range: arterial pressure is increased, heart rate is unchanged, central venous pressure is increased, cardiac failure is unusual. The abdominal distension is also responsible for a restrictive respiratory syndrome, mainly due to the ascension of the diaphragm. The compression of the abdominal content explains renal effects and the decreased diuresis. A sustained increase in abdominal pressure occurs in several clinical conditions. During coelioscopy, abdominal pressure is a under control and the cardiovascular effects are minor. Insufflation with CO2 carries the risk of hypercapnia, gas embolism and pneumothorax. During abdominal tamponade, anuria is directly related to the level of pressures. At an abdominal pressure over 25 mmHg, anuria is common and decompression becomes essential. The G suit increases arterial pressure either by elevating vascular resistances or increasing blood content in the upper part of the body. Therefore cardiac tolerance can be decreased especially in cardiac patients. The adverse effects of abdominal pressure can also be observed in case of peritoneal dialysis and ascites. The risk of regurgitation associated with an increased abdominal pressure must also be kept in mind. The abdominal pressure plays an important role in anaesthesia as well as in surgery. Therefore its measurement, which is easy, should become a routine. PMID- 7992946 TI - [Bilateral sensorineural hearing loss after general anesthesia]. AB - A bilateral sensorineural (perceptive) deafness occurred in a 12-year-old girl, following laparoscopic appendicectomy under general anaesthesia not comprising nitrous oxide and low insufflation pressures and a normal haemodynamic status. There was neither a personal nor a familial history of hearing disturbances nor a preoperative intake of ototoxic drugs. The initial loss of 50 dB has been substantiated by evoked auditive potentials. The treatment consisted of hyperbaric oxygenotherapy and vasodilators. The girl recovered completely. Finally the etiology of this complication remained unrecognized. Possibly the CO2 insufflated into the abdominal cavity could be considered. However, its causative effect remains to be proven. PMID- 7992947 TI - [Hemodynamic diagnosis of aortocaval fistula complicating abdominal aortic aneurysm]. AB - A 78-year-old man with a history of hypertension was admitted for a fall with back pain. The blood pressure was at 110/50 mmHg and the pulse at 115 b.min-1. A pulsatile abdominal mass was palpated. No signs of respiratory insufficiency or congestive heart failure were found. The diagnosis of abdominal aortic aneurysm was promptly confirmed by echography. Before laparotomy, a pulmonary artery catheter was inserted for haemodynamic monitoring which showed a high cardiac output, low systemic vascular resistances, increased pulmonary artery wedge pressure and a high SvO2 (93%). This was not consistent with a hypovolaemic shock but rather an aortocaval fistula. After incision and aortic clamping, surgical procedure consisted of transaortic closure of the fistula and restoration of arterial continuity with a prosthetic graft. Initial control of venous bleeding was obtained by passing a Foley's catheter distally and by clamping the vena cava. The postoperative course was initially satisfactory. The patient was extubated, but remained with a major renal insufficiency. After a stay of 15 days in the intensive care unit, he died from nosocomial pneumonia. Aortocaval fistulas are either traumatic or spontaneous. Spontaneous fistulas are more common, and in about 90% of the cases result from a rupture of an atherosclerotic aortic aneurysm. Clinical findings include signs of high cardiac output symptoms of venous hypertension and regional arterial insufficiency. Haemodynamic changes can be of value for the recognition of an aortocaval fistula. Most authors emphasize the importance of preoperative diagnosis, allowing the use of appropriate operative techniques and a prompt control of the fistula. This could decrease haemodynamic instability and transfusion requirements. PMID- 7992948 TI - [State of shock during acute meprobamate poisoning. 6 cases]. AB - The prognosis of acute meprobamate poisoning is related to shock whose haemodynamic mechanism remains obscure. We report the results of a retrospective study of six patients with meprobamate poisoning associated with shock and explored by a right heart catheterization. The age of the patients, five women and one man, ranged from 36 to 57 years. Five patients had also ingested other psychotropic drugs. A haemodynamic investigation was performed at admission to the ICU and three hours later, under treatment. Vasoplegia was the predominant feature. A myocardial dysfunction was sometimes associated, which can be explained by a moderate hypothermia. According to these results, we suggest that prior to right heart catheterization, the treatment should include inotropic and alphamimetic agents and that vascular filling should be cautious. PMID- 7992949 TI - [Hypertensive episode and arrhythmia with fatal outcome caused by pheochromocytoma discovered peroperatively]. AB - The authors report a case of pheochromocytoma recognized during surgery, at the manipulation of the tumor resulting in severe arterial hypertension, arrhythmia and a final unresponsive ventricular fibrillation. The anatomopathological examination confirmed the diagnosis of the pheochromocytoma in ectopic localization. PMID- 7992950 TI - [Pulmonary edema occurring 2 days after elective cesarean section]. AB - Two days after an elective Caesarean section, a 30-year-old woman suffered a pulmonary oedema. The diagnosis of cardiomyopathy was obtained with echocardiography, right heart catheterization and a myocardial biopsy. Peripartum cardiomyopathy is defined as a heart failure occurring in the last trimester of pregnancy or up to the third postpartum month and the lack of another etiology. The cause of myocarditis resulting in peripartum cardiomyopathy remains yet unknown. An immunosuppressive therapy can be associated with the treatment of the congestive heart failure. PMID- 7992951 TI - [Angioneurotic edema and anesthesia: preparation and perioperative monitoring]. AB - Hereditary angioneurotic oedema is an autosomal dominant disease associated with serum deficiency of functional C1-inhibitor. It is characterized by periodic swelling of subcutaneous tissues, abdominal viscera and upper airways. Lethal acute episodes of oedema can occur during anaesthesia and surgery. It is essential to prepare such patients before surgery. This article describes three cases (kidney transplantation, caesarean section, normal delivery) and the various preventive measures used to avoid acute episodes during anaesthesia and surgery. Antibrinolytic agents, androgens, fresh frozen plasma, C1-inhibitor concentrate can be administered. Their various indications are discussed. PMID- 7992953 TI - [Surgery for epidermolysis bullosa in children: value of the association of inhalation anesthesia and locoregional anesthesia]. AB - Due to the cutaneous and mucosal fragility associated with epidermolysis bullosa, this disease is a source of various practical problems for the anaesthesiologist concerning the surgical posture, the monitoring of vital functions, the airways control and the vascular access, as all these procedures may worsen, sometimes dramatically, the lesions in these young patients, still in a precarious health state. Basing on published studies and their own experience, the authors have used in these patients a combined locoregional and general anaesthesia. The latter was obtained with isoflurane, administered in the non intubated and spontaneously breathing patient through a closed surgical isolation container (Vi Drape), including the patient's head and ventilated with a ventilator generating a PEEP for long procedures. The results obtained during 9 procedures in 3 children are reported and discussed. For several shorter procedures (for example wound dressing), intramuscular ketamine was used. PMID- 7992952 TI - [An unusual cause of pericardial effusion during pleural drainage]. AB - A 66-year-old man was admitted for mitral valve replacement required by a mitral regurgitation resulting in a severe heart failure. He also suffered from chronic respiratory failure, related to a left concavity cyphoscoliosis. Postoperatively, hypoxemia occurred. His chest X-ray showed a left pleural effusion indicating a percutaneous pleural drainage. A local anaesthesia with a 21 G needle was performed prior to drain insertion, which was easily introduced into the pleural cavity. A few minutes later, the patient experienced an acute haemorrhagic shock. He was immediately transferred into the operating room, where the cardiac surgeon discovered and treated a coronary artery effraction. The vascular lesion was attributed to the needle used for local anaesthesia. The patient was discharged twelve days later without sequelae. Two factors were responsible for this accident: the patient's cyphoscoliosis and his left ventricle enlargement. This complication is uncommon. However, in case of a particular patient's anatomy, it is suggested to use a score devised to anticipate the risk of a difficult pleural drainage. This score should include general, thoracic, spinal, cardiac, hepatic and splenic morphology. PMID- 7992954 TI - [Hydrofluoric acid: an unrecognised toxic agent]. AB - Hydrofluoric acid has widespread uses in industry and at home. Its mechanism of toxicity is the basis of a specific treatment. Cutaneous burns are the most common form of toxicity and the consequences can be catastrophic. Its insidious presentation can delay any therapeutic action, except if the physician is aware about it. A case report underlines the beneficial action of the intra-arterial infusion of calcium gluconate. PMID- 7992955 TI - [Epidural "ambulatory" anesthesia]. PMID- 7992956 TI - [Analgesia after laparoscopy: value of intraperitoneal administration of sodium chloride solution]. PMID- 7992958 TI - [Minute ventilation or tidal volume?]. PMID- 7992957 TI - [3 in 1 block associated with local and intra-articular infiltration for fascicular nailing of the hip]. PMID- 7992959 TI - [Etiology of cardiac arrest with massage in prone position]. PMID- 7992960 TI - [The SFAR logo and the "golden number", comments (continued)]. PMID- 7992961 TI - [Who knows Hood? Wanted!]. PMID- 7992962 TI - The simple Fogarty embolectomy: an operation of the past? AB - We have found in reviewing our vascular cases that the Fogarty embolectomy is definitive treatment in only certain types of cases; in most it is an adjunct to more complex vascular surgery. In our cases, an embolectomy catheter was used as an integral part of the procedure in 130 (18%) cases. In 96 (74%) cases, an embolectomy alone was performed with a success rate of only 48% (46 cases). In 50 (52%) cases, the embolectomy was not adequate, requiring reoperation, a new bypass, or amputation within 7 to 10 days. Mortality rate for the series of 130 patients was 7.0%, and limb loss rate was 5.0%. The majority of cases (92) in this review were diagnosed with an acute exacerbation of diffuse peripheral vascular disease or a clotted graft, and it is in these patients that the success rate was so poor (17%) if embolectomy alone was performed. The population of patients presenting with suspected acute arterial insufficiency has changed over the past 30 years. Now it is the elderly who have an acute exacerbation of their peripheral vascular disease. It is this change in the population that has made the Simple Fogarty Embolectomy an operation of the past--mandating angiography, Fogarty embolectomy, and complex vascular reconstruction for limb salvage. PMID- 7992963 TI - Postpneumonectomy chylothorax: a logical approach to successful management. AB - Chylothorax is unusual as a postoperative complication following pneumonectomy. Although rare today, it can still manifest life-threatening consequences if not recognized and treated in a timely and appropriate manner. Management options range from a conservative approach to immediate re-exploration, each of which has been reported as successful. However, treatment of this entity has been characterized as ill-defined or controversial despite the fact that most approaches to this clinical problem are similar. A successful outcome of this unusual complication is presented based on early recognition and institution of logical principles of conservative management. Treatment should be neither ill defined nor controversial. PMID- 7992964 TI - Peripherally-placed central venous access ports: clinical and laboratory observations. AB - The P.A.S. Port system is a totally implantable central venous access device consisting of a miniature titanium portal and a 5.8 French catheter that is specifically designed for implantation in the forearm. The configuration of this system combined with its unique placement technology provides a simplified alternative to conventional chest-placed systems. Our group has placed a total of 61 P.A.S. Port devices in 56 patients whose ages ranged from 9 months to 85 years and who were followed for a median of 672 days. Over this period of follow-up, these devices have demonstrated a low overall complication rate (13.1%), an infection rate of 6.6%, median event-free patency of 278 days, and exceptional patient acceptance. Placement of the P.A.S. Port system is easily performed as an outpatient procedure under local anesthesia and requires neither fluoroscopy nor a conventional operating room setting. In vitro measurement of infusion pressure across a P.A.S. Port and a conventional catheter system revealed much higher resistance in the peripherally placed device, but this was found to be of no clinical significance because infusion pressures generated by flow rates up to 750 mL/hr were well within the limits of clinically available infusion pumps. We recommend the P.A.S. Port system as a safe, durable, and effective alternative for patients in whom a chest-placed device is inappropriate or undesired. PMID- 7992965 TI - An evaluation of symptoms and performance status in patients after esophagectomy for esophageal cancer from the viewpoint of the patient. AB - We used a questionnaire method to investigate the complaints and the life conditions of 81 patients after esophagectomy for esophageal cancer. Patients were separated into three groups according to their follow-up time: less than 2 years, more than 2 years but less than 5 years, and more than 5 years after surgery. The distribution of complaints was similar regardless of the time elapsed since surgery. Only 22% of all patients had no complaints. Abdominal fullness and stenotic sensation were the major complaints. Body weight was unstable for 2 years following surgery, but subsequently stabilized. The content of meals, volume of meals, and Performance Status (PS) did not differ significantly among the groups and were indicative of satisfactory recovery. Our results suggest that in contrast to other surgeries, postoperative symptoms persist in esophagectomyed patients with long survival and that about half of the cases whose follow-up time was less than 2 years have unstable body weight. PMID- 7992966 TI - Primary non-Hodgkin's lymphoma of the duodenum. AB - Primary non-Hodgkin's lymphoma of the duodenum is an uncommon primary tumor of the gastrointestinal (GI) tract. Diffuse, large cell lymphoma of B-cell origin is currently recognized as representing the predominant histologic type of primary extranodal lymphoma arising in a gastrointestinal site. Three patients are presented with primary lymphoma arising in the second (two) and fourth (one) portions of the duodenum. Two patients with Stage I-E disease were treated by pancreaticoduodenectomy followed by postoperative radiotherapy, and remain without recurrence at 8 and 6 years. A third patient with Stage II-E disease of the fourth portion of the duodenum was treated with total resection of all bulky disease followed by chemotherapy without radiotherapy. However, this patient died after 46 months. The literature is reviewed, with emphasis on the use of surgical resection in the treatment of non-Hodgkin's lymphoma of the duodenum. PMID- 7992967 TI - Liver metastases from colorectal carcinoma: incidence, resectability, and survival results. AB - We studied 328 cases of colorectal carcinoma (stages I-IV) seen at our hospital during a 19-year period. We found that 15% of these had liver metastasis (LM) at initial diagnosis, and 14% developed LM after resection of their primary cancers. Among the 73 patients with LM, the lesion was confined to the liver (LM only) in 40 patients. Using our criteria of "resectability" of LM, 45% with LM only had resectable LM lesions, but only 15% (six patients) actually had hepatic resections. We had no operative death nor major complication. Five of the six patients with LM resected lived 3 years or longer, but none of the other 34 patients with LM only (either non-resectable or resectable but not operated on) lived more than 35 months. Although our series is relatively small, our data are consistent with results coming from other national and institutional studies. The controversies and issues relating to resection of colorectal liver metastasis are discussed. PMID- 7992968 TI - A simple stapling technique for prosthetic repair of massive incisional hernias. AB - This article introduces a simpler, faster, and safer method of performing the Stoppa procedure with an articulating stapler. It also encourages use of preperitoneal repair instead of the often unsuccessful onlay mesh repair. The latter repair involves placing the mesh over the abdominal aponeurotic layer and can result in a high incidence of infection, seroma accumulation, and chronic fibrous cyst formation. In the preperitoneal repair technique, the same force that created the hernia--the intraabdominal hydrostatic pressure--keeps the mesh tightly in place and prevents recurrence of the hernia. The authors base their recommendation of the stapling technique on the experience of 54 large incisional hernias successfully repaired by preperitoneal insertion of a large sheet of Marlex mesh (Stoppa's procedure). In 29 of the 54 patients, the mesh was fixed in place with hand suturing. In the other 25, articulating staplers attached the mesh. The authors have found the stapling technique to be both simpler to accomplish and safer for the patient. PMID- 7992969 TI - Management of anomalous rotation in adults. AB - Rotational anomalies of the gut are infrequently encountered in the adult population. Management of this population is debatable because of a few anecdotal reports and small patient series. We present the successful surgical correction of a patient with symptomatic nonrotation and review our experience with six asymptomatic patients with anomalous rotation discovered incidentally at laparotomy for another disease process. The incidence of anomalous rotation is reported as high as 0.5% in autopsy series. Therefore, a large majority of subjects are clinically silent throughout life. Although a surgical emergency in the pediatric population, serendipituous discovery in the asymptomatic adult does not require surgical intervention. It is important, however, that the patient have a thorough understanding of his abnormality so that should symptoms arise, urgent surgical intervention may be warranted. We recommend appendectomy in those patients undergoing laparotomy for other conditions. In patients with chronic abdominal symptoms, surgical intervention is warranted. PMID- 7992970 TI - The use of adjunctive thrombolytic therapy in the management of acute popliteal aneurysm thrombosis. AB - Acute thrombosis of a popliteal aneurysm frequently results in limb loss due to thromboembolic occlusion of the tibioperoneal "outflow" tract. In these patients, the best prognostic indicator of limb salvage is the patency status of the tibioperoneal vessels. When these outflow vessels are occluded at arteriography, intraarterial fibrinolytic therapy may reestablish outflow when none is present preoperatively, thereby allowing the opportunity for dependable distal reconstructive surgery and thus limb salvage. PMID- 7992971 TI - Rapid right atrial cannulation for fluid infusion during resuscitative emergency department thoracotomy. AB - A simple rapid technique for cannulating the right atrium during a resuscitative Emergency Department thoracotomy (EDT) for exsanguinating trauma is described. Following the thoracotomy and pericardiotomy, an ordinary Foley urinary bladder balloon catheter is inserted into the right atrial appendage for rapid, large volume normothermic blood and fluid infusion. A method for simplifying this maneuver, as well as the potential complications of over-resuscitation with myocardial distention and fluid overload, myocardial cooling, air embolism, and tricuspid valve occlusion are discussed. We recognize that this technique is radical and applicable to only a limited subset of severely injured patients, for example, victims of non-cardiac penetrating trauma who arrive at the hospital moribund or who arrest in the emergency center. PMID- 7992972 TI - Emergency appendectomies in patients over 80 years. AB - The outcome of 100 consecutive emergency appendectomies between 1985 and 1991 in octogenarians was compared to an unselected group of equal size, composed of patients between 60-79 and under 59 years. The frequency of appendectomies in the elderly did not increase during the study period. Negative explorations were performed in 28%-33% of the three age groups. The mortality was 0%, 3%, and 7%, and the complication rates 10%, 23%, and 40% in the patients aged under 59, between 60-79, and over 80 years, respectively. Appendiceal perforation was found in 49% of octogenarians, and it was associated with the mortality rate of 21%. In conclusion, patients under 80 years with emergency appendectomy had acceptable low mortality and morbidity rates that were comparable to the results of elective abdominal surgery of the same age, but the octogenarians had higher risk of poor outcome. PMID- 7992973 TI - Sepsis-induced alterations in the erythrocyte membrane. AB - Sepsis is known to alter red blood cell (RBC) deformability, and this change in flexibility may play a role in the pathophysiology of the hemodynamic alterations characteristic of the septic syndrome. The etiology of this red cell change is unclear. This study evaluates erythrocyte size and cell membrane fluidity during clinical (septic surgical patients) and experimental (endotoxin incubation) sepsis. Membrane lipid viscosity was assessed by fluorescent spectroscopy. Mean corpuscular volume and hemoglobin concentration was determined by automated counter. There was a significant increase in erythrocyte membrane lipid viscosity (P < 0.001) in both the clinical and experimental septic models. No difference was detected, however, in RBC mean corpuscular volume or hemoglobin concentration. These findings suggest that sepsis-induced alterations in erythrocyte deformability are due primarily to an increase in the membrane lipid viscosity and are unrelated to alterations in the cell surface area to volume ratio. PMID- 7992974 TI - Pseudomyxoma retroperitonei associated with appendiceal cystadenoma. AB - Pseudomyxoma peritonei is a rare condition in which the peritoneal cavity is full of thick gelatinous deposits, thought to represent a tumor of varying degrees of malignancy. Most cases originate from ruptured ovarian cysts or appendiceal mucoceles, and involve the intraperitoneal cavity alone. There have only been two previously reported cases of extraperitoneal pseudomyxoma in the English literature. This report describes a case of pseudomyxoma retroperitonei arising from an appendiceal mucinous cystadenoma. The pathologic elements of the disease process, as well as treatment options, are discussed. PMID- 7992976 TI - Advantages of outpatient breast surgery. AB - This article outlines surgical, financial, and psychosocial advantages of outpatient, definitive breast cancer surgery. The analysis of 118 patients who underwent outpatient breast cancer surgery between January 1991 and December 1993 -20 modified radical mastectomy, 90 lumpectomy and axillary dissection or axillary dissection alone, and 8 partial or simple mastectomy--revealed only three patients with minor complications requiring admission. Same-day discharge was safely accomplished by early morning admission and using recovery room time for postoperative education. Outpatient cost was $1572 compared with an average 3 day inpatient cost of $6282, for a potential savings of $4710, or 75%, per patient for modified radical mastectomy. Outpatient cost was $1080 compared with an average 2-day inpatient cost of $4907, for a potential savings of $3827, or 78%, per patient for lumpectomy with axillary node dissection. Patients have indicated a high level of satisfaction with ambulatory surgery and experienced faster healing and recovery at home within the family milieu. PMID- 7992975 TI - Coexistent abdominal aortic aneurysm and renal carcinoma: management options. AB - Renal carcinoma (RCA) presenting in association with abdominal aortic aneurysm (AAA) is extremely rare, with only sporadic case reports previously described. The management of six cases of AAA and concomitant RCA presenting to a single institution from March, 1991 through December, 1993 was reviewed and management options considered. AAAs ranged in size from 4.5-7.0 cm (mean, 5.6 cm). Three left renal carcinomas were resected via a retroperitoneal approach simultaneous to repair of the AAA. One right renal carcinoma was resected in combination with repair of an AAA through a transperitoneal approach. The fifth case was managed by left nephrectomy, followed by interval aneurysmectomy, and the sixth case was managed by nonsurgical methods because of the presence of widely metastatic disease. Renal malignancies included five renal cell carcinomas and one transitional cell carcinoma. Three patients remain free of disease 8-11 months postoperatively, and one patient had metastatic disease detected 19 months postoperatively. Two deaths have occurred; one due to a massive CVA 1 month following a combined aneurysmectomy and left nephrectomy, and a second due to unknown etiology in the patient managed non-surgically. No peripheral vascular or aortic graft related complications have occurred. The treatment of AAA and RCA should be governed by the size of the AAA, the location of the cancer, and the extent of malignant disease. Simultaneous resection is safe and effective in patients with coexistent AAA and renal cancer. Left sided tumors should be resected via a retroperitoneal approach that also provides excellent exposure for simultaneous AAA resection.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7992977 TI - Laparoscopic cholecystectomy in the inner-city hospital. AB - Laparoscopic cholecystectomy (LCCY) has become the treatment of choice for patients undergoing elective CCY. Inner-city hospitals treat a large number of patients with advanced or acute disease, and the ability to perform LCCY in this patient population is unclear. The records of the first 107 patients undergoing LCCY were reviewed. There were 96 women and 11 men with a mean age of 42 years (range 14-86 years). Twenty-seven (42%) of the patients were admitted through the emergency room and were operated upon urgently, whereas 35 (58%) underwent elective LCCY. More than two-thirds of the patients were either uninsured or covered by Medicaid. In the urgent group, 38% had gallstone pancreatitis, 41% had abnormal LFTs, and 26% had a WBC > 13,000. A total of 70% of these patients were discharged within 48 hours after LCCY. The conversion rate was 9% and was similar between urgent and elective LCCY. In summary, acute biliary tract pathology accounted for one-half of the patients undergoing LCCY in our hospital. In conclusion, LCCY can be performed in this group of patients with low morbidity, especially if the need for liberal conversion to open CCY is recognized. PMID- 7992978 TI - Missile embolization revisited: a rationale for selective management. AB - Embolization of missiles is an unusual presentation of penetrating trauma. Often the management of these injuries may be quite challenging, and selective management continues to be subject to controversy. We report a case of a bullet embolus to the right ventricle from the internal iliac vein in a 15-year-old boy that was managed with observation. An algorithm for diagnosis and management of this phenomenon mandates exploration of emboli to the aorta and peripheral arteries with repair of the vascular entry site and embolectomy. It also recommends operative intervention for symptomatic venous emboli to the heart and pulmonary circulation. Nonoperative management may be considered in patients with asymptomatic emboli to the right heart or the cerebral and pulmonary circulation. PMID- 7992979 TI - Tumor-induced ileo-ileal invagination in adults. AB - We report two cases of ileo-ileal intussusception due to a lymphoma in a 25-year old and a leiomyoma in a 35-year-old woman. Both were diagnosed by laparotomy. Intussusception is a rare condition in adults and is usually difficult to diagnose. In contrast to childhood, idiopathic intussusception is quite rare in adults. The etiology is usually an intestinal tumor. In adults treatment is always surgical. PMID- 7992981 TI - Conservative management of endoscopic sclerotherapy-induced esophageal perforation. AB - Esophageal perforation is a rare though potentially lethal complication of variceal sclerotherapy. Diagnosis is usually made after recognition of often subtle clinical symptoms. Surgical and nonsurgical modalities have been proposed, and nonoperative management can be successful even in patients thought to have absolute indications for surgery. PMID- 7992980 TI - Villous adenoma of the vermiform appendix with cecal intussusception: a case report and review of literature. AB - Villous adenoma of the appendix is an uncommon neoplasm. Intussusception of the appendix is a rare pathological entity. We report here an intussusception of the appendix, the lead point being a villous adenoma, presenting in a 62-year-old male whose initial complaint was a progressive enlargement of a right inguinal hernia. The endoscopic, surgical, and pathologic data are presented. A review of the literature of this uncommon entity is also presented. PMID- 7992982 TI - "What will the poor boys at LSU do without me?" An account of the death of Senator Huey P. Long. PMID- 7992983 TI - A mechanism for pentamidine-induced hyperkalemia: inhibition of distal nephron sodium transport. AB - OBJECTIVES: To determine whether pentamidine directly affects the transport of renal ions and thus provides a mechanism for hyperkalemia, which develops in as many as 100% of patients with the acquired immunodeficiency syndrome (AIDS) who receive pentamidine for more than 6 days. DESIGN: Transepithelial and single channel electrical measurements were made on two models of distal-nephron ion transport: an amphibian distal-nephron cell line (A6) and primary cultures of rabbit cortical collecting tubules. RESULTS: Luminal bath application of pentamidine to A6 monolayers inhibited the amiloride-sensitive, short-circuit current with a 50% inhibitory concentration of 700 microM (five experiments). In the principal cell apical membranes of cortical collecting tubule primary cultures, amiloride-sensitive, 4-picosiemen Na+ channels in cell-attached patches were also identified. When the luminal membrane was directly exposed to 1.0 microM of pentamidine in the patch pipette solution, channel activity decreased by 40% (11 experiments). Channel inhibition rapidly reversed with washout of intrapipette pentamidine (four experiments). In contrast, replacement of either the luminal bath outside the patch pipette (four experiments) or the serosal bath (five experiments) with pentamidine did not significantly affect Na+ channel activity in the patches. CONCLUSIONS: Luminal or "urinary" pentamidine inhibits distal nephron reabsorption of Na+ by blocking apical Na+ channels in a manner similar to "potassium-sparing" diuretics (for example, amiloride and triamterene). This results in a decrease in the electrochemical gradients that drive secretion of distal nephron K+. Because pentamidine is eliminated through urinary excretion, this renal tubular effect provides a mechanism for pentamidine induced hyperkalemia. PMID- 7992985 TI - The ciguatera poisoning syndrome from farm-raised salmon. PMID- 7992984 TI - The irritable bowel syndrome: long-term prognosis and the physician-patient interaction. AB - OBJECTIVE: To evaluate the long-term course and prognosis associated with the irritable bowel syndrome (IBS) and to determine the influence of an effective physician-patient relationship on subsequent health care use. DESIGN: Prospective review of medical records. SETTING: Tertiary referral center. PATIENTS: 112 consecutive Olmsted County, Minnesota, residents who were first diagnosed with IBS at the Mayo Clinic during the period 1961-1963. RESULTS: The median follow-up was 29 years (range, 1 to 32 years) and patients made a median of 2 return visits for IBS-related symptoms (range, 0 to 12 visits). In addition to abdominal pain, diarrhea (reported by 50% of patients) was the predominant bowel symptom at diagnosis. Organic gastrointestinal disease occurred in 10 patients a median of 15 years after diagnosis of IBS. Survival in patients with IBS did not differ from expected survival (27 deaths; median survival > 30 years after initial diagnosis). A positive physician-patient interaction, defined a priori using objective criteria in the written record, was associated with fewer return visits for IBS. Of the eight variables examined, notations in the medical record about psychosocial history, precipitating factors, and discussion of diagnosis and treatment with patients were associated with fewer return visits for IBS-related symptoms. CONCLUSIONS: When diagnosed according to current criteria, IBS is associated with a good prognosis and the diagnosis is unlikely to be changed to that of an organic disease during follow-up. A positive physician-patient interaction may be related to reduced use of ambulatory health services by patients with IBS. PMID- 7992986 TI - Genetic testing in the diagnosis and management of multiple endocrine neoplasia type II. AB - PURPOSE: To review significant advances in the early diagnosis and treatment of medullary thyroid carcinoma in patients with the multiple endocrine neoplasia II (MEN II) syndromes, advances made possible by the application of recently discovered genetic information. DATA SOURCES: Recently published English-language literature on linkage analysis and DNA analysis in the MEN II syndromes. STUDY SELECTION: Articles on familial and sporadic forms of medullary thyroid carcinoma; pentagastrin-calcitonin determination; and genetic testing. DATA EXTRACTION: Information from recent studies on 1) the usefulness and limitations of genetic testing, especially DNA and linkage analysis, in the early diagnosis of the familial form of thyroid carcinoma and 2) the correlation between the results of genetic testing and the results of biochemical screening. DATA SYNTHESIS: Medullary thyroid carcinoma accounts for most of the morbidity and mortality among patients with the familial medullary thyroid carcinoma syndromes. Multiple endocrine neoplasia IIa and IIb and familial medullary thyroid carcinoma are inherited conditions with autosomal dominance and incomplete penetrance. Traditionally, diagnosis and screening for these conditions have been done using pentagastrin stimulation tests and plasma calcitonin determinations. Recent genetic mapping, however, has assigned the genes responsible for these tumors to the pericentromeric region of chromosome 10. Available data suggest that mutations in exon 10, 11, or 16 of the RET proto-oncogene are responsible for MEN IIa and IIb and familial non-MEN medullary thyroid carcinoma. Thus, genetic testing can identify affected members of a kindred and will probably lead to early thyroidectomy and possible cure for gene carriers. CONCLUSIONS: Early studies confirm the usefulness of DNA analysis in the diagnosis and treatment of patients with familial forms of medullary thyroid carcinoma. We review changes in the diagnosis and treatment of these patients and offer a strategy for operative intervention based on results of genetic testing. PMID- 7992987 TI - Comparing hospital mortality in adult patients with pneumonia. A case study of statistical methods in a managed care program. AB - OBJECTIVE: To compare and contrast a managed care program's analysis of differences in hospital mortality with results obtained by accepted statistical methods. DESIGN: A re-analysis of computerized discharge data using the same method used by a managed care program, and using conventional methods of categorical data analysis. One thousand computer simulations of a method for comparing hospitals by severity-adjusted mortality were done to determine the probability of falsely identifying hospitals as high-mortality outliers. SETTING: 22 acute care hospitals in central Pennsylvania. PATIENTS: All adult patients with pneumonia (n = 4587; diagnosis-related groups 089-090) less than 65 years of age who were discharged from the 22 hospitals in 1989, 1990, and 1991, excluding patients with the acquired immunodeficiency syndrome and transplant recipients. MEASUREMENTS: In-hospital mortality adjusted for age and severity of illness using MedisGroups admission severity group score. RESULTS: The hospital that had the highest mortality for adult pneumonia according to the managed care program's analysis did not, according to an appropriate analysis, differ significantly from other area hospitals (likelihood ratio test, P = 0.23). Random variation in this sample of patients with a low average mortality rate (3.5%) showed a 60% chance that 1 or more of the 22 hospitals would be falsely identified as a "high mortality outlier" when simplistic statistical methods were used. CONCLUSION: Organizations seeking to compare the quality of hospitals and physicians through outcome data need to recognize that simplistic methods applicable to large samples fail when applied to the outcomes of typical patients, such as those admitted for pneumonia. Although these comparisons are much in demand, careful attention must be paid to their statistical methods to ensure validity and fairness. PMID- 7992988 TI - Effects of antihypertensive therapy on serum lipids. AB - PURPOSE: To compare and contrast the effects of antihypertensive agents on serum lipids and blood pressure in different patient populations. DATA SOURCES: A MEDLINE search and bibliographies from recent comprehensive reviews were used to identify trials that provided sufficient data to calculate the change in one or more serum lipid values measured before and after antihypertensive therapy. STUDY SELECTION: 474 controlled and uncontrolled clinical trials investigated the effects of 85 antihypertensive agents on lipids and blood pressure in more than 65,000 patients. DATA EXTRACTION: Data on triglyceride and total, low-density lipoprotein (LDL), and high-density lipoprotein (HDL) cholesterol levels; blood pressure; patient characteristics; and study design. DATA SYNTHESIS: Differences in the effects of agents, adjusted for differences in patient populations and study design, were examined using multiple linear regression analysis that was weighted by study quality and inverse variance. Diuretics caused relative increases in cholesterol levels (regression coefficient = 0.13 mmol/L; 95% CI, 0.09 to 0.18 mmol/L) that were greater with higher doses (additional effect of high dose, 0.12 mmol/L; CI, 0.04 to 0.20 mmol/L) and were worse in blacks than in nonblacks (additional effect in blacks, 0.13 mmol/L; CI, 0.01 to 0.26 mmol/L). Beta-blockers caused increases in triglyceride levels (0.35 mmol/L; CI, 0.31 to 0.39 mmol/L) that were substantially smaller for agents with intrinsic sympathomimetic activity (amelioration of beta-blocker increase, -0.21 mmol/L; CI, -0.27 to -0.16 mmol/L). When combined with cardioselectivity, beta-blockers with intrinsic sympathomimetic activity favorably affected lipids and reduced both total (-0.14 mmol/L; CI, -0.24 to -0.04 mmol/L) and LDL cholesterol levels ( 0.17 mmol/L; CI, -0.28 to -0.07 mmol/L). alpha-Blockers beneficially affected total cholesterol (-0.23 mmol/L; CI, -0.28 to -0.18 mmol/L), LDL cholesterol ( 0.20 mmol/L; CI, -0.25 to 0.15 mmol/L), triglycerides (-0.07 mmol/L; CI, -0.11 to -0.03 mmol/L), and, in younger persons, HDL cholesterol (0.02 mmol/L; 0.01 to 0.04 mmol/L). Converting enzyme inhibitors reduced triglycerides (-0.07 mmol/L; CI, -0.12 to -0.02 mmol/L), and, in patients with diabetes, total cholesterol ( 0.22 mmol/L; CI, -0.34 to -0.10 mmol/L). Vasodilators reduced total (-0.22 mmol/l; CI, -0.30 to -0.10 mmol/L) and LDL cholesterol (-0.22 mmol/L; CI, -0.29 to -0.11 mmol/L) and increased HDL cholesterol (0.06 mmol/L; CI, 0.02 to 0.09 mmol/L). CONCLUSION: With the exception of calcium antagonists, nearly all antihypertensive agents affect serum lipids. These effects differ among patient populations. PMID- 7992989 TI - Respirators, recommendations, and regulations: the controversy surrounding protection of health care workers from tuberculosis. AB - Recent nosocomial outbreaks of tuberculosis have increased concern about the occupational acquisition of tuberculosis by health care workers. The Centers for Disease Control and Prevention (CDC), Department of Health and Human Services, and the Occupational Safety and Health Administration, Department of Labor, have issued recommendations and regulations in an effort to decrease health care workers' risk for exposure to patients with infectious tuberculosis. Within the CDC, the National Center for Infectious Diseases, the National Center for Prevention Services, and the National Institute for Occupational Safety and Health collaborated to produce the 1994 Guidelines for Preventing the Transmission of Tuberculosis in Health-Care Facilities. As stated in the Draft Guidelines, the major components of health care worker protection from Mycobacterium tuberculosis infection include administration or source controls, engineering controls, and respiratory protective devices. We review the evolution of the seemingly conflicting recommendations for respiratory protective devices made by these Centers of the CDC and explain how the recommendations in the current CDC Guidelines were reached. PMID- 7992990 TI - Minocycline treatment of rheumatoid arthritis. PMID- 7992991 TI - The measure and mismeasure of hospital quality: appropriate risk-adjustment methods in comparing hospitals. PMID- 7992992 TI - Plague in India: a new warning from an old nemesis. PMID- 7992993 TI - Transmission of hepatitis C virus to spouses. PMID- 7992994 TI - Prinzmetal angina and cyproheptadine. PMID- 7992995 TI - Screening for ovarian cancer. PMID- 7992996 TI - Chronic severe hemolytic anemia from phenazopyridine. PMID- 7992997 TI - Chronic severe hemolytic anemia from phenazopyridine. PMID- 7992998 TI - Joseph Goldberger: unsung hero. PMID- 7992999 TI - The internist's reading: purposeful eclecticism. PMID- 7993000 TI - Minocycline in rheumatoid arthritis. A 48-week, double-blind, placebo-controlled trial. MIRA Trial Group. AB - OBJECTIVE: To assess the safety and efficacy of minocycline in the treatment of rheumatoid arthritis. DESIGN: A double-blind, randomized, multicenter, 48-week trial of oral minocycline (200 mg/d) or placebo. SETTING: 6 clinical centers in the United States. PATIENTS: 219 adults with active rheumatoid arthritis who had previous limited treatment with disease-modifying drugs. MEASUREMENTS: As the primary outcomes, 60 diarthrodial joints were examined for tenderness, and 58 joints were examined for swelling (hips excluded). Grip strength, evaluator's global assessment, morning stiffness, Modified Health Assessment Questionnaire, patient's global assessment, hematocrit, erythrocyte sedimentation rate, platelet count, and IgM rheumatoid factor levels were also assessed; radiographs of both hands and wrists were taken. RESULTS: 109 and 110 patients were randomly assigned to receive minocycline and placebo, respectively. At entry, demographic, clinical, and laboratory measurements were similar in both groups. Most patients had mild to moderate disease activity and some evidence of destructive disease. At the week 48 visit, 79% of the minocycline group and 78% of the placebo group continued to receive the study medication. At 48 weeks, more patients in the minocycline group than in the placebo group showed improvement in joint swelling (54% and 39%) and joint tenderness (56% and 41%) (P < 0.023 for both comparisons). The minocycline group also showed greater improvement in hematocrit, erythrocyte sedimentation rate, platelet count, and IgM rheumatoid factor levels (all P values < 0.001), and more patients receiving minocycline had laboratory values within normal ranges at 48 weeks. For the remaining outcomes, P values ranged from 0.04 to 0.76, all greater than the critical value of 0.005 (Bonferroni adjustment for multiple comparisons). The frequency of reported side effects was similar in both groups, and no serious toxicity occurred. CONCLUSIONS: Minocycline was safe and effective for patients with mild to moderate rheumatoid arthritis. Its mechanisms of action remain to be determined. PMID- 7993001 TI - Efficacy of control measures in preventing nosocomial transmission of multidrug resistant tuberculosis to patients and health care workers. AB - OBJECTIVE: To assess the efficacy of control measures in decreasing nosocomial transmission of multidrug-resistant tuberculosis. DESIGN: Retrospective cohort study. SETTING: A teaching hospital in New York City. POPULATION: 40 patients hospitalized with multidrug-resistant tuberculosis (case-patients) and health care workers receiving tuberculin skin testing. INTERVENTIONS: Centers for Disease Control and Prevention (CDC) 1990 guidelines for preventing transmission of tuberculosis, including 1) prompt isolation and treatment of patients with tuberculosis; 2) rapid diagnostic techniques for processing Mycobacterium tuberculosis specimens; 3) negative-pressure isolation rooms; and 4) molded surgical masks for health care workers. MEASUREMENTS: Proportion of case-patients with nosocomially acquired tuberculosis and rate of tuberculin skin test conversion among health care workers before and after implementation of control measures. RESULTS: The proportion of patients with multidrug-resistant strains of M. tuberculosis decreased after the interventions (10 of 70 [14%] compared with 30 of 95 [32%] patients before the intervention; relative risk [RR], 0.5; 95% CI, 0.2 to 0.9). Before onset of multidrug-resistant tuberculosis, case-patients in the intervention period were as likely to be hospitalized on high-risk wards containing patients with tuberculosis (4 of 10 compared with 17 of 30 patients; RR, 0.7; P = 0.5) but were less likely to be exposed to another case-patient with tuberculosis (1 of 10 compared with 20 of 30 patients; RR, 0.2; P = 0.003). Tuberculin skin test conversion rates for health care workers assigned to wards housing patients with tuberculosis were lower in the intervention period than in the preintervention period (4 of 78 [5%] compared with 15 of 90 [17%] conversions; P = 0.02), decreasing to levels observed for workers assigned to other wards (4 of 78 [5%] compared with 9 of 228 [4%] conversions; P = 0.7). CONCLUSIONS: Implementing control measures reduced nosocomial transmission of multidrug-resistant strains to patients and health care workers. PMID- 7993003 TI - On being a Professor Emeritus. 1944. PMID- 7993002 TI - Unrecognized myocardial infarction: epidemiology, clinical characteristics, and the prognostic role of angina pectoris. The Reykjavik Study. AB - OBJECTIVE: To evaluate the incidence, prevalence, characteristics, and prognosis associated with clinically unrecognized myocardial infarction as diagnosed by electrocardiographic changes. DESIGN: Prospective, population-based cohort study with 4- to 20-year follow-up. SETTING: Icelandic Heart Association Preventive Clinic. PARTICIPANTS: 9141 men residing in the Reykjavik area who were born between 1907 and 1934. MEASUREMENTS: Patients were assigned to categories of coronary heart disease at first visit on the basis of hospital records, Rose chest pain questionnaire, standardized 12-lead electrocardiogram, and history and physical examination. Incidence and prevalence of unrecognized myocardial infarction were determined, survival was measured, and causes of death were determined from death certificates and autopsy records. RESULTS: Prevalence was strongly influenced by age. Nearly undetectable in the youngest age group, it increased to more than 5% in the group aged 75 to 79 years. Incidence was almost zero up to age 40, then increased steeply to more than 300 cases per year per 100,000 persons at age 60, and decreased with age after age 65. Ten- and 15-year survival probabilities were 51% and 45%, respectively, and were similar to those for patients with recognized myocardial infarction. One third of men with unrecognized and 58% of men with recognized myocardial infarction had a history of angina pectoris (P < 0.001). Angina pectoris had a greater effect on coronary heart disease mortality in the former group than in the latter. The risk ratio for unrecognized myocardial infarction was 4.6 without angina (95% CI, 2.4 to 8.6) and 16.9 with angina (CI, 9.4 to 30.3); the risk ratio for recognized myocardial infarction was 6.3 without angina (CI, 3.7 to 10.6) and 8.5 with angina (CI, 5.8 to 12.6). CONCLUSION: At least one third of all myocardial infarctions were unrecognized. Prognosis and risk factor profiles for patients with recognized and unrecognized myocardial infarction were similar. Although those with unrecognized myocardial infarction were less likely than those with recognized myocardial infarction to have a history of angina pectoris, angina in these cases was usually associated with ischemic electrocardiographic changes and a poor prognosis, suggesting severe coronary heart disease. PMID- 7993004 TI - Tracheoesophageal voice following tubed free radial forearm flap reconstruction of the neopharynx. AB - Tracheoesophageal voice restoration after laryngectomy is possible with a variety of neopharyngeal reconstructions. We have used the tubed radial forearm free flap for neopharyngeal reconstruction since 1991. Six patients have undergone voice restoration with the Blom-Singer prosthesis and were available for quantitative and qualitative speech analysis. These patients were compared to five laryngectomy patients with standard pharyngeal closures and similar voice restorations. The free flap patients produced similar loudness levels compared to the standards with soft speech (52.06 dB and 47.19 dB, respectively) and loud speech (62.66 dB and 60.91 dB, respectively). The free flap patients demonstrated adequate intelligibility, with fundamental frequencies comparable to standards (124.82 Hz and 135.66 Hz, respectively), although with increased jitter (5.00% versus 1.96%). No differences were statistically significant, but evaluation by trained and naive listeners demonstrated significant differences in voice quality. This quantitative and qualitative and qualitative analysis of tracheoesophageal speech after radial forearm free flap reconstruction of the neopharynx demonstrates that acceptable voice can be achieved, but with limitations. PMID- 7993005 TI - Dynamic properties of the posterior cricoarytenoid muscle. AB - The aim of this research was to investigate the contractile properties of the posterior cricoarytenoid (PCA) muscle. Simultaneous measurements were made of the isometric force, temperature, and electromyographic activity of the dorsal cricoarytenoid muscle of anesthetized dogs during supramaximal stimulation of the recurrent laryngeal nerve for twitch and tetanic contraction. The conduction delay between stimulation of the recurrent nerve at the level of the larynx and the onset of the muscle action potential averaged 2.0 +/- 0.2 milliseconds (ms), and the latent period between the onset of electrical activity of the muscle and the onset of contraction had a mean duration of 3.3 +/- 0.8 ms. The mean of isometric contraction times found was 33.3 +/- 2.0 ms, shorter than most previous studies of canine PCA muscle. Tetanic frequency defined as smooth contraction was higher than previous estimates. Considerations of scaling of physiological time based on animal mass were applied to analysis of the experimental findings to make possible systematic comparison of previous findings across species and animal size. PMID- 7993006 TI - Statistical analysis of otosclerosis surgery performed by Jean Marquet. AB - The early and long-term hearing results of 1,681 primary otosclerosis operations performed by the same surgeon, Jean Marquet, were reviewed retrospectively and analyzed with very strict statistical standards. Significantly better short- and long-term results were achieved with the stapedotomy technique compared to total stapedectomy, mainly at the higher frequencies (4 and 8 kHz) important for speech discrimination. Whatever technique was used to open the footplate (micropick, microdrill, or laser), no statistical audiometric difference could be found. The results were equal whether or not the stapedial tendon was preserved. Perioperative problems like pronounced oozing, difficult anatomic relationships, and accidental perilymph aspiration could affect hearing at higher frequencies. The calibrated hole technique was equally as good as conventional oval window sealing in sealing of the fenestra to prevent fistula. The stapedotomy technique was found the safest, having fewer complications. PMID- 7993007 TI - Endoscopic resection of the intranasal frontal sinus floor. AB - The current accepted treatment for chronic frontal sinus disease unresponsive to medical management and endoscopic surgery is an external approach to either obliterate the sinus or restore communication to the nasal cavity. Here reported is an endoscopic approach for resection of the intranasal frontal sinus floor, a modification of a procedure first described by Lothrop in 1899. Eleven patients underwent this operation from April 1993 to December 1993. One complication, a cerebrospinal fluid leak treated successfully endoscopically, has occurred. Of the 7 patients followed up 3 months or longer after surgery, only 1 has developed symptoms of recurrent frontal sinusitis. On the basis of this limited preliminary experience, the endoscopic Lothrop procedure shows promise as an effective operation designed to establish a physiologic communication between the frontal sinus and the nasal cavity in selected patients who would otherwise be candidates for an external approach. PMID- 7993008 TI - Changes in cerebrospinal fluid pressure in daily life. AB - The purpose of the present study was to measure changes in cerebrospinal fluid pressure (CSF-P) during actions of daily life. A spinal tap was performed on 23 inpatients. During the procedure, the patients were requested to perform the following four actions: nose blowing with one side closed, nose blowing with both sides closed, breath holding, and sniffing. The CSF-P was recorded before and during these actions. Of these, nose blowing with both sides closed resulted in the greatest elevation of pressure. Three patients with perilymph fistula showed larger changes than the other 20 patients. Conversely, sniffing lowered the CSF-P in all cases. The present study suggests that daily physical actions cause significant elevations of CSF-P. Such changes may be responsible for the development of perilymph fistula. PMID- 7993009 TI - Healing of incisions in the tongue: a comparison of results with milliwatt carbon dioxide laser tissue welding versus suture repair. AB - The healing of carbon dioxide laser weld closures produced by two commercial instruments of differing design were compared. Healing after laser welding was also compared to healing following conventional suture closure. Healing was evaluated histologically and by measurement of tensile strength over time. No histologic differences were found between closures produced by different lasers; however, in all cases suture closure resulted in slower healing times consistent with a foreign body reaction prolonging the healing process. Tensile strength measurements were performed at intervals over the first 21 days after the operation. Laser repair was found to be equivalent to or stronger than suture repair at every interval measured. The clinical use of the carbon dioxide laser for tissue welding of oral injuries should be investigated further, since it appears to be a good alternative to suture repair. PMID- 7993011 TI - Auditory effect of kanamycin given to newborn guinea pigs whose mothers received kanamycin during pregnancy. AB - Clinical and experimental data indicate that aminoglycoside ototoxicity occurs more frequently in individuals previously exposed to ototoxic drugs. This study investigated the auditory effect of repetitive administration of kanamycin on newborn guinea pigs that had previously been exposed, in utero, to kanamycin administered to their mothers. Sixteen pregnant guinea pigs in the late stages of gestation were divided into two groups, one receiving kanamycin 500 mg/kg per day intramuscularly for 8 days, and the other acting as a control. After birth, the mothers and their newborns in both groups were examined for auditory brain stem response (ABR) and then treated with kanamycin 500mg/kg per day for 4 days. The results from the second examination demonstrated that the group receiving prior treatment with kanamycin, despite their good ABR responses during the first measurement, showed significantly elevated auditory thresholds compared to the control group. Therefore, any ototoxic drugs should be used with extreme caution in newborns having had prior exposure to the drugs in utero, even if they have a "normal" auditory response after birth. PMID- 7993010 TI - Function of the interarytenoid muscle in a canine laryngeal model. AB - The interarytenoid (IA) muscle has rarely been studied in the living larynx. In this work, the role of the IA muscle in phonation was studied in three dogs by means of an in vivo phonation model. The isolated action of the IA muscle was studied by sectioning and stimulating its nerve branch. As IA activity increased, subglottic pressure increased significantly until a plateau was reached. In the absence of superior laryngeal nerve stimulation, the fundamental frequency rose with increasing IA activity. In the presence of superior laryngeal nerve stimulation, however, no significant change in fundamental frequency was observed with increasing IA activity. Measurement of adductory force demonstrated that the IA muscle adducts primarily the posterior vocal fold. In this canine model, phonation was not possible without IA stimulation, owing to a large posterior glottic chink. PMID- 7993012 TI - Lingual abscess. PMID- 7993013 TI - Orbital decompression for Graves' disease complicated by sinusitis. PMID- 7993014 TI - [Organization of liver transplantation in France]. AB - Liver transplantation (LT) is performed in 27 centres in France, including 7 in Paris. Two of these centres (Cochin and Bicetre) have a large paediatric activity, either exclusively or alongside adult transplantation. An organ harvesting activity is very often associated with LT. Except for one centre (Strasbourg), LT is associated with other surgical activities. The distribution of livers complies with national rules established by transplanters who have defined priorities in the context of a system based successively on regional priorities then national priorities. A ministerial decree and 6 executive decrees govern the organisation of LT in France, the conditions necessary for accreditation, as well as the modalities of evaluation which, for the moment, remain fairly theoretical. LT activity is important in France: 697 LTs in 1991, including 315 in Paris. Its development, or even its maintenance depends on the volume donor organs. The future law on bioethics will have a decisive importance on the subsequent development of liver transplantation. PMID- 7993015 TI - [Preoperative assessment of liver transplantation. Contribution of imaging]. AB - Medical imaging plays an essential role in the preoperative assessment of liver transplant patients to detect any lesions contraindicating the operation or to detect any anatomical variants in the recipient likely to lower the chances of success of the transplantation. At the present time, the imaging techniques useful in the preoperative assessment are colour Doppler ultrasound, abdominal CT scan and coeliac and superior mesenteric arteriography. The calibre and patency of the portal trunk and its branches, the hepatic artery at the porta hepatis, the hepatic veins and their distribution and the inferior vena cava are systematically evaluated. Systematic identification of the various portosystemic shunts in the context of portal hypertension helps to define a veritable preoperative map. PMID- 7993016 TI - [Therapeutic attitude in adult recipients waiting for liver transplantation]. AB - Any new therapeutic procedure raises the question of its possible interference with a possible liver transplantation. This management must therefore give a change to medical treatments of complications of liver disease without interfering with the possibility of subsequent liver transplantation. The treatment of the complications related to chronic liver disease: gastrointestinal haemorrhage, ascites, ascitic infection are examined from this point of view. The necessity of repeated investigation for hepatocellular carcinoma and the importance of maintaining a correct nutritional status are recalled. The elements of monitoring and treatment which can interfere with the planned transplantation are examined in patients with alcoholic cirrhosis, chronic active viral hepatitis B, sclerosing cholangitis, autoimmune chronic active hepatitis or hepatocellular carcinoma. In fulminant hepatitis, the administration of drugs and any form of clotting factor is prohibited due to the particular risk of altering regular reassessment of the level of consciousness and hepatocellular function. Don't transplant those who are going to recover and don't transplant too late those who are not going to recover. PMID- 7993017 TI - [Transjugular intrahepatic portasystemic shunt and liver transplantation]. AB - From the first one hundred consecutive patients treated by transjugular intrahepatic portosystemic shunt (TIPS), 12 subsequently underwent liver transplantation (a mean of 103 +/- 109 days after TIPS). Fourteen TIPS were created in 12 patients, with advanced cirrhosis (Child B = 5, C = 7) and portal hypertension. Seven patients presented either active variceal hemorrhage or refractory variceal bleeding, and 5 cases of refractory ascites. The shunt could be performed in all cases. Two patients experienced rebleeding (one after a shunt obstruction) and were successfully treated by insertion of a second TIPS. A histological study was performed in 10 cases. The shunt was patent in all cases (except in one case previously described), and the endoluminal surface was covered by a connective tissue layer and a new endothelium. We therefore conclude that this method is a safe and effective therapy for complications of portal hypertension, in patients referred for liver transplantation. PMID- 7993018 TI - [Intrahepatic anatomy. Application to liver transplantation]. AB - In transplantation of the whole liver, the variable shape of the organ can exceptionally be the source of difficulties, as in the rare cases of situs inversus. Arterial variants may be the source of great difficulties. Among the biliary variants, the low junction of the right and left hepatic ducts in the main portal pedicle, and especially the cysto-hepatic ducts (entrance of a right duct into the gallbladder or the cystic duct) are particularly important, with a frequency ranging from 2 to 15% of the cases. Right liver--left liver, or right liver--left lobe bipartition is now a well controlled technique. Right lobe, left lobe bipartition should never be performed. The left hepatic vein is attributed to the left transplant (left liver or left lobe). In case of duplication of the left vein, the terminal portion of the middle vein is attributed to the left transplant, and the continuity of the middle vein with the inferior vena cava must be reconstructed. The middle vein is always attributed to the right transplant. When the portal bifurcation is missing, usually bipartition is impossible. When the right portal vein is duplicated, the portal stem is attributed to the right liver. Duplications of right and left arteries and ducts make difficulties. A thorough preoperative investigation is necessary in case of a living donor. Cholangiography and arteriography on the back table are essential to achieve an ex vivo bipartition. The surgeon then disposes of three manoeuvres: resection of segment IV, attribution of a short segment of the main duct on the side of a biliary duplication, attribution of the main hepatic artery (or the celiac axis) on the side of a left transplant (left liver or left lobe) is possible in 86% of cases, ex vivo is possible in 95. 70% of cases. Tripartition of the liver is not yet a controlled technique. PMID- 7993019 TI - [Intensive care and perioperative monitoring in liver transplantation]. AB - Perioperative intensive care has several objectives in the context of liver transplantation. Prior to the operation, it is essential for the management of fulminant hepatic failure in order to limit the consequences of cerebral oedema. During the operation, intensive care consists of monitoring and correction of the occasionally severe circulatory and metabolic disorders induced by vascular exclusion of the liver and revascularization of the cold, ischaemic, orthotopic transplant. The possibility of major haemorrhage requiring massive transfusion with stored blood aggravates these disorders. Complex clotting disorders also play an important role; their mechanism is imperfectly understood and they are difficult to control. The severity of the problems encountered after the operation depends on graft function. PMID- 7993020 TI - [Liver transplantation, vascular complications, role of imaging, percutaneous therapeutic possibilities]. AB - Duplex Doppler ultrasound should be the first investigation when a vascular complication is suspected. Serial examinations may increase sensitivity. Color imaging enhances identification of small vessels and increases specificity. Angiography is not necessary unless an pseudoaneurysm is suspected. When duplex Doppler ultrasound is abnormal, angiography is performed to evaluate the possibility of treatment. Endovascular therapeutic procedures appear to have a limited field of application in comparison to percutaneous biliary procedures. Hemostatic embolization or dilatation of vascular strictures can be used either as definitive treatment or while waiting for a new graft to be performed under better conditions. PMID- 7993021 TI - [Vascular complications of liver transplantation: surgical treatment]. AB - Vascular complications constitute a major cause of morbidity and mortality after liver transplantation. They are dominated by arterial complications, the most frequent being hepatic artery thrombosis. Venous complications essentially consist of portal vein thrombosis. The preventive treatment of vascular complications is based on a better understanding of the risk factors. Close cooperation between surgeon, and radiologist is essential for effective surgical correction, which requires a rapid diagnosis and is designed to save not only the patient's life, but also, whenever possible, the liver transplant. PMID- 7993022 TI - [Biliary complications after liver transplantation. Contribution of imaging- percutaneous treatment]. AB - Biliary complications are observed in 7 to 20% of orthotopic liver transplantations. Biliary strictures and fistulas are the commonest complications, usually at the site of anastomoses, or more rarely at a distance. The entire transplant biliary tract may be affected, particularly in the case of hepatic artery thrombosis. These lesions are due to multifactorial ischaemic phenomena. Mechanical complications can occur after insertion of a Kehr drain. Mucoceles of the cystic duct, responsible for extrinsic bile duct compression, are much less common. The diagnosis is based on medical imaging, as the clinical signs are often non-specific. Ultrasonography has limited sensitivity as a first line examination. Opacification of the bile ducts is therefore essential at the slightest doubt, as it has a sensitivity of 100% and allow assessment of the lesions. Transhepatic cholangiography is preferable to retrograde opacification due to the risks infection. CT scan is useful in the case of fistula to assess fluid collections. Percutaneous treatment avoids the need for open surgery in about 1/3 of cases. Strictures can be dilated by means of inflatable balloons, via a percutaneous or retrograde approach. Intra-abdominal collections can be drained percutaneously. PMID- 7993023 TI - [Technique of biliary reconstruction in liver transplantation and surgical treatment of complications]. AB - Reconstruction of the biliary tree is the last step of a liver transplant procedure. The two techniques currently used are anastomosis of the common bile ducts with or without a Kehr drain and anastomosis to a Roux-en-Y jejunal limb. The latter procedure is usually done when the former is not feasible (missing or abnormal bile duct in the recipient). Biliary complications still occur in 5% to 25% of liver transplant recipients. The most common are fistulas and, above all, stenosis of the anastomosis. Treatment usually requires a surgical procedure to repair the anastomosis, drain a fistula, or perform a Roux-en-Y jejunal anastomosis. However, some complications are amenable to endoscopic or percutaneous treatment. PMID- 7993024 TI - [Imaging of complications of liver transplantation in children]. AB - The authors report their experience of imaging of 286 liver transplantations (LT) in children. Hepatic artery thrombosis is the most serious complication (9%), with a maximum risk during the first two weeks. Its clinical presentation is very variable and its diagnosis is based on Doppler ultrasonography. Emergency surgical disobstruction prevented the development of biliary or ischaemic complications in one half of cases. Portal thrombosis (4.5%) is due, in the majority of cases, to hypoplasia of the recipient's portal vein. Patency of intrahepatic portal branches with inversion of flow can delay the ultrasonographic diagnosis. Biliary complications are frequent (20%) and occur after a very variable interval. Their diagnosis is ultrasonographic, but sometimes delayed compared to the histological signs. Transhepatic cholangiography visualises the lesions and allows external drainage or even percutaneous dilatation. In 1 out of 4 cases, the aetiology was hepatic artery thrombosis. The imaging protocol after LT consists of ultrasonography with daily Doppler (or even twice-daily) in the patient's bed for the first two weeks and then as required. Computed tomography is useful to demonstrate parenchymal ischaemia and intraperitoneal abscess in multi-operated children. Angiography and cholangiography confirm the ultrasonographic signs. Interventional Radiology plays an increasingly important role. PMID- 7993025 TI - [Infectious complications after liver transplantation]. AB - Infections after liver transplantation are frequent and represent the first cause of mortality. Bacterial and fungal infections are favourized by preoperative clinical status, surgical conditions, degree of immunosuppression, and surgical complications. Perioperative antibiotics and, for patients at risk, antifungal prophylaxis, reduce their indicidence. Viral infections are attributed principally to CMV. Prophylaxis against CMV with immunoglobulins can be suggested for patients at risk. Curative antiviral treatment is always effective. PMID- 7993026 TI - [Ascites after liver transplantation in children]. AB - The objective of this study, based on a series of 148 transplants performed in 131 children, was to evaluate the frequency, complications and predisposing factors of ascites occurring after liver transplantation (LT). The diagnosis of post-LT ascites was defined as a drainage rate greater than 25 ml/kg/day (or- > 500 ml/day) persisting for at least 72 hours after removal of the drains. Among the 123 transplants analysed, 31 (25.2%) were complicated by ascites (group I). Group II consisted of 92 LT without ascites. This ascites was predominantly lymphocytic (669 +/- 1,104/mm3), rich in proteins (32 +/- 13 g/l), with a low triglyceride concentration. The mean duration of ascites was 25 +/- 19 days. Complications of ascites included: infection of ascitic liquid (35%), respiratory complications (65%), parietal complications (50%), consumption coagulopathy (35%), functional renal failure (Creat > 130 mumol/l, 35%). There were 9 deaths (29%) in group I versus 8 in group II (p < 0.02). The predictive factors, pre-LT, of postoperative ascites included: serum bilirubin > 300 mumol/l (p < 0.02); PT < 30% (p < 0.05); and serum albumin < 30 g/l (p < 0.05). Intraoperative factors favouring the development of ascites were end-to-side cavo-caval implantation of the graft when it was reduced (p < 0.02) and a volume of transfused blood after unclamping greater than 60 ml/kg (p < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7993027 TI - [Complications and liver transplantation: diagnostic strategy]. AB - Liver transplantation is currently the treatment of choice for end-stage liver failure in children and adults. 670 liver transplantations were performed in France in 1990. The 2-year survival rate in adults is 65%. Significant progress in terms of survival has been achieved as a result of improvement of surgical techniques and postoperative surveillance, the development of effective immunosuppressant therapy and a better organization of donor organs. Surgical techniques depend on the recipient and the transplant available. Imaging is useful in pretransplantation assessment, but especially during the immediate and long-term follow-up to assess transplant vitality and to detect any complications, which are of four types: vascular, biliary, or related to rejection or infection. Postoperative surveillance of the transplant must be based on a diagnostic approach conducted according to the following optimal sequence: laboratory parameters, histological examination and imaging, performed systematically from the 1st day onwards, including examination of the hepatic parenchyma, bile ducts, hepatic vessels and search for effusions and collections. The role of imaging in the context of rejection is not so much to visualize of rejection, as to eliminate a vascular, biliary or even infectious cause for the altered laboratory parameters. In the context of surgical vascular, biliary, infectious or complex complications, the examination sequence always includes clinical and laboratory findings, histology, angiography in the context of vascular complications and CT scan to assess the vitality of the hepatic parenchyma and to identify any intrahepatic or perihepatic collections. Interventional radiology plays an important role in the treatment of these vascular, biliary and infectious complications and should be considered prior to any surgical revision. PMID- 7993028 TI - [Measurement of the volume of the liver by 3D computed tomography with anatomic correlation]. AB - The purpose of this prospective study is to evaluate the accuracy of the volume measurement of the liver by three dimensional computed tomography (CT 3D). Volumetric studies were performed using axial data obtained in 12 cases during conventional dynamic CT and 8 cases during spiral CT with contrast enhancement examination. All patients were selected for liver transplantation. Volume of the liver and left and right lobes was obtained on 3D CT images after thresholding and ROI manual contour segmentation on CT slices and integrated 3D reconstruction software. Reference volume of recipient liver was obtained by means of water deplacement after transplantation. The segmental anatomy on CT slices and recipient liver was defined as described by Couinaud. Comparison by means of linear regression analysis between volume measurement on CT 3D reconstruction and reference volume showed a nearly ideal correlation coefficient (R = 0.996) (p < 0.01). CT3D reconstruction for measuring liver or segmental liver volume can be applied in extensive hepatic surgery or partition liver transplantation with adult donor with the necessary sensitivity. PMID- 7993029 TI - [Perspectives of liver replacement: consideration of the uniqueness of the human liver]. AB - The feasibility of liver replacement is currently dominated by the problems of availability of liver transplants. This has led to the development of surgical techniques allowing the use, in children, of a transplant derived from an older donor, whose volume is reduced by partial hepatectomy. Transplant sharing techniques have also been developed allowing the same donor organ to be used in two recipients. Despite the negative aspects of this approach, some teams have also been forced to develop liver transplantation in children using a living related donor. With the possibility of a growing shortage of transplants, research is underway in the field of heterologous transplantation, i.e. interspecies transplantation. Control of rejection is currently the principal obstacle in this context and is a long way from being completely resolved. PMID- 7993030 TI - [Towards a decrease of myocardial infarction in the Bas-Rhin region? Results of the 6 first years of the Strasbourg MONIC Register]. AB - The Bas-Rhin MONICA Register shows trends in myocardial infarction and other acute ischemic events between 1984 and 1989. Coronary heart disease mortality decreased by 27% in men and 30% in women. Morbidity trends were less favourable. The annual event rate for total acute ischemic events remained stable. However, a decrease of 14% for myocardial infarction was seen in men, particularly in patients with a past history of coronary disease. Another positive point is that the 28-day mortality rate in recent infarctions decreased in men by 33% during the 5 year period. PMID- 7993032 TI - [New approach for implantation of automatic defibrillators using videothoracoscopy]. AB - Nonthoracotomy lead systems are increasingly used in patients (pts) with implantable cardioverter defibrillator (ICD). In this setting, due to high energy requirements, a subcutaneous patch may be necessary in addition to endocardial leads. However in some patients, high defibrillation threshold (DT) may persist leading to thoracotomy for epicardial patch placement. In a preliminary experience, 3 patients with high DT (> 20 J) following endocardial lead system, underwent the insertion of a extrapericardial patch under video-thoracoscopic control. A left subcostal incision extended to the left pleural cavity was performed. Using thoracoscopy the patch was positioned on the pericardium, sutured and connected to the defibrillator. DTs were 10, 10 and 20 J respectively in our 3 patients. Postoperative course was uneventful. Thoracoscopy allows other techniques such as a stellectomy, which we performed in a 33 year old woman with long QT syndrome. Patients were reassessed after 8 days and 2 months. Termination of induced ventricular fibrillation was achieved with the same minimal energy levels used peroperatively. In conclusion, extrapericardial patch insertion using thoracoscopy may help reduce DT in ICD patients with a non thoracotomy lead system. Comparison with other lead configurations requires further investigation. PMID- 7993031 TI - [Tracheobronchial healing after lung and heart-lung transplantations. Apropos of 64 anastomoses]. AB - The authors report an analysis concerning the healing of tracheo-bronchial anastomoses after lung- and heart-lung transplantation. The present study includes 64 anastomoses selected from a total of 80 cases. Sixteen had to be excluded because of early post-operative death; none of these deaths was related to an air-way complication. Bronchial healing was assessed by bronchoscopic follow-up; the appearance of the suture-line was classified according to Couraud's grades. The initial reference was the examination at 2 weeks, which was compared to subsequent follow-up. At the initial assessment, 42 anastomoses were grade 1, 4 were grade II, and 18 were grade III. The subsequent anatomic result was satisfactory for 52 sutures (81%). The complications were malacia in 2 cases, stenoses treated with a stenting device in 4 cases, dehiscence in 6 cases. The duration of ischemia and postoperative mechanical respiratory support, as well as the proximal or distal site of the anastomosis appeared to be of significant prognostic value. PMID- 7993033 TI - [Ventricular decompression and neuropsychiatric disorders in coronary surgery]. AB - The marked decrease in neuropsychiatric morbidity (NPM) following coronary artery bypass (CAB) over a period of four years led us to carry out a retrospective study in order to identify the cause. Two hundred fifty-eight consecutive CAB procedures were performed between 1983 and 1986. For 133 patients (group A), the CAB procedure was performed with left ventricular vent (LVV) and for 125 patients (group B) without LVV. In group A, 93 patients (group A1) had cardiopulmonary bypass (CPB) with a bubble oxygenator and 40 patients (group A2) had CPB with a membrane oxygenator. In group B, 30 patients (group B1) had CPB with a membrane oxygenator without filter in the arterial line and 95 patients (group B2) had CPB with a membrane oxygenator and filter in the arterial line. The reduction in NPM arose from the removal of the LVV, as the incidence of NMP was in group A 24.6% versus 12.3% in group B (p < 0.05). The substitution of the bubble oxygenator by a membrane oxygenator does not alter the incidence of NPM: 23.3% in group A1 versus 27.5% in group A2 (p > 0.05) nor did incorporation of a filter in the arterial line: 10% in group B1 versus 13.1% in group B2 (p > 0.05). Introduction of air in the left ventricle via an LVV catheter opening and coronary arteriotomy therefore causes gazeous microembolic events responsible for NPM following CAB. PMID- 7993034 TI - [Recovery of healthy and hypertrophied hearts after global ischemia and gradual reperfusion]. AB - The influence of pressure controlled reperfusion on the postischemic outcome of normal and normotensive hypertrophied rat hearts should be investigated. To induce normotensive cardiac hypertrophy, male Wistar rats received injections of isoprenaline (5 mg/kg s.c. bid for three days). Hearts were excised and perfused in the Langendorff-technique at a perfusion pressure of 75 mmHg for 30 min. After cardioplegia and 40 min of global ischemia at 25 degrees C the hearts were reperfused for 45 min. Reperfusion pressure was built up either abruptly (75 mmHg immediately) or gradually (from 40 mmHg to 75 mmHg within 30 min). Postischemic recovery was significantly affected by the mode of reperfusion in normal hearts where pressure controlled (gradual) reperfusion is superior to the abrupt reperfusion mode. In hypertrophied hearts the postischemic outcome did not differ from normal hearts if abrupt reperfusion was used, but gradual reperfusion only led to a comparably small amelioration of postischemic status. PMID- 7993035 TI - [Abdominal aortic aneurysm binds less albumin-I-125 the atheromatous aorta]. AB - The causes of abdominal aortic aneurysm are still poorly understood. The author studied the permeability of the aneurysm wall or the aortic wall in 21 patients with abdominal aortic aneurysm or aorto-iliac bypass by comparing 125I-albumin tissue concentrations; The results suggest that albumin crosses the aneurysm wall less easily than that of the atheromatous aorta. PMID- 7993036 TI - [Thromboses of heart valve prostheses: predisposing and prognostic factors based on a study of 41 patients]. AB - Forty one patients were admitted with a diagnosis of prosthetic valve thrombosis. One patient was thrombolyzed successfully, and 40 underwent surgical procedures. In 13 cases, prosthetic valve thrombosis occurred in the first month after valve replacement. 18 patients were in functional class IV of the NYHA classification. Among the thrombosed prostheses, 91% were mechanical, and 61% in mitral position. Adequacy of anticoagulation was the most important risk factor, as this treatment was inappropriate in 20 patients. In 10 other patients, it had been changed for medical (bleeding events, pregnancy) or surgical (non cardiac surgery) reasons. The perioperative mortality rate was high (32.4%). It was 12% in patients in functional class II and 46% in those in class IV (p < 0.05). This underlines the value of early diagnosis, in which echocardiography, especially with a transesophageal probe, takes a major place, allowing prompt surgical treatment. PMID- 7993037 TI - [Left ventricular hypertrophy in hypertensive patients]. AB - Left ventricular hypertrophy associated with hypertension is characterised by an increase in ventricular mass, secondary to hypertrophy of myocardial cells and to the development of collagen tissue and capillaries. Easily detectable by electrocardiography, it occurs in 30 to 60% of hypertension patients, in a concentric form with symmetric or asymmetric thickening of the walls, or in an eccentric form with dilatation of the ventricular cavity. It impairs the functional properties of the myocardium, first affecting diastolic function then, later, systolic function. It interferes with the coronary circulation, with a decrease in coronary reserves and hypoperfusion of subendocardial layers. It predisposes to the onset of ventricular and supraventricular arrhythmias. It is a major and independent risk factor, severely marring the prognosis of hypertension sufferers. PMID- 7993038 TI - HIV--Australasian experience. Oral manifestations of HIV infection and their clinical management. PMID- 7993039 TI - Treatment of the refractory case. PMID- 7993040 TI - A comparison of aesthetic inlay systems. AB - A comparison of the aesthetic inlay systems available to the dental practitioner is made. The methods of fabrication of the various types of inlay are described, together with the reasons for utilization of the inlays. The indications and the contra-indications for prescribing these systems are listed, and the advantages and disadvantages of the inlays are enumerated. The clinical technique for the inlays is briefly outlined, and the use of resin luting cements is reviewed. PMID- 7993041 TI - The Hunter years. PMID- 7993042 TI - Aspects of dentinal and pulpal pain. Pain of dentinal and pulpal origin--a review for the clinician. AB - Recent advances in understanding the mechanisms of pain arising from the dental pulp serve to benefit patients by improving the clinician's ability to diagnose and treat pain. There are two types of pain arising from the pulp which are mediated by entirely different nerve fibres, each with their own individual characteristics. One is a short, sharp fast pain which is induced by stimuli which cause a rapid fluid flow within the dentinal tubules. Such stimuli include cold, heat, air, drilling, and osmotic stimuli. Once the affected teeth are identified, they can often be treated by sealing the open, exposed dentine. The second type of pain is experienced as a slow, dull, aching, poorly localized pain which is mediated by pain fibres activated by stimuli which are noxious to the pulp, such as prolonged damaging heat and inflammatory mediators. Pain of this character can be difficult to diagnose and often indicates serious pulp damage necessitating removal of the offending pulp by endodontic therapy. PMID- 7993043 TI - Aspects of dentinal and pulpal pain. Diagnosing dental pain. AB - Patients present with a large variety of different pain patterns. Some types of pain will be quite excruciating and intolerable whereas other types of pain will be low grade, annoying but quite tolerable. It is only by carefully going through the complete history with the patient and using the appropriate test or tests that one can accurately diagnose the pain and positively treat the offending tooth. PMID- 7993044 TI - Aspects of dentinal and pulpal pain. Force, cracks and restorative dentistry. AB - The human dentition is subject to many and varied destructive forces which decrease the longevity of the individual tooth and dentition. This article is a review of the forces placed on the dentition during function and the potentially more damaging parafunction and the effect restorative dentistry plays on weakening tooth structure. This will be related to the cracked tooth syndrome, its diagnosis and subsequent treatment. PMID- 7993045 TI - Treatment planning for the mixed dentition malocclusion--treatment and goals. AB - The mixed dentition stage of development may provide a useful window of opportunity to embark upon orthodontic therapy to correct an isolated malocclusion or provide preliminary treatment as a precursor to more comprehensive therapy at a later stage of the patient's physical development. As in all forms of orthodontic treatment, the planning of any correction must be carried out with care so that meaningless tooth movement can be avoided. Growth modification procedures can also be considered during this stage of development but, as this is connected intimately to increased height velocity, these procedures are most usefully carried out in the late mixed dentition, or more frequently in the early permanent dentition as this coincides more closely with peak height velocity. Several studies have suggested that approximately 20 per cent of patients presenting with a malocclusion can be treated appropriately during the mixed dentition. There would appear to be a genuine risk of falling off in cooperation levels in needed, permanent dentition treatment in many patients who have experienced one or more treatment procedures at an earlier stage in dental development. These findings reinforce the need for careful treatment planning during the mixed dentition. PMID- 7993046 TI - Orthodontics through the ages: from six to sixty. PMID- 7993047 TI - Aetiology and management of the anterior dislocated disc. The anterior dislocated disc: some considerations of aetiology and clinical diagnosis. AB - The displacing temporomandibular joint disc presents an enigma. Modern imaging techniques of arthrography, CT, and MRI, as well as arthroscopy show that a displaced or even totally dislocated disc is not necessarily associated with disease, and such a joint can function quite without symptoms. Conversely these techniques, and notably arthroscopy, show that in some cases trauma initiates a cascade of events affecting not only the disc but also synovium, capsule, ligaments, and cartilage. Changes in synovial fluid, alterations in collagen, and associated release of pain-producing substances, cause alteration in joint dynamics. Reversible at early stages, these processes can produce adhesions which alter joint movement, including disc displacement. There is no single cause of disc displacement, but rather the effect of trauma on the interplay between structural, behavioural, and orthopaedic factors. Clinical diagnosis, excluding imaging, is briefly discussed emphasizing the concept of the barrier, and the use of diagnostic manipulation. PMID- 7993048 TI - Aetiology and management of the anterior dislocated disc. Management of articular disc displacement. AB - There is considerable disagreement among clinicians regarding the appropriate management of articular disc displacement. Research findings are difficult to interpret and compare because of the multitude of clinical variables. A number of questions remain unanswered. Is articular disc displacement truly pathology? Is diagnosis by clinical signs and symptoms adequate and accurate? Do we need to 'reposition' the disc and, if so, can we? Is reciprocal clicking a reliable sign of disc displacement and does it require treatment in the absence of other signs and symptoms? This article presents a short review of the more recent literature and provides guidelines for appropriate treatment. PMID- 7993049 TI - Periodontics--1990 and onwards. PMID- 7993050 TI - Placement of implants into immediate extraction sites: a review. PMID- 7993051 TI - Medicine and dentistry: the dawn of the fourth age. AB - Medicine-bashing is in vogue; but is there substance behind the empty 'sound bites'; cheap shots and screaming headlines, or is it all just political rhetoric? This essay examines some of the issues and tries to place the costs and technologicalization of medicine and dentistry in a perspective of historical development. The truth is that there is much truth in the criticisms. Howsoever, this is not a jeremiad essay--solutions to our problems exist and they are not Utopian--the real question is whether we are able to learn and put into our practice our lessons. PMID- 7993052 TI - Sodium hyaluronate for temporomandibular joint disorders. PMID- 7993053 TI - Improving the accuracy of orthognathic surgery. AB - The advent of modern techniques for the correction of facial deformity has allowed oral and maxillofacial surgeons to routinely perform facial bone osteotomies to correct facial deformities and malocclusions. As these techniques have become more commonplace there is an ever increasing need for accuracy to fulfil the expectations of patients, orthodontists, and surgeons. Attention to detail is 'the name of the game'. This paper will highlight points of detail in the preparation, planning, and execution of facial bone osteotomies to improve the outcome for patients with facial deformities. PMID- 7993054 TI - The stability of the downgrafted maxilla in the cleft lip and palate patient. AB - Vertical stability following maxillary downgrafting in cleft patients is poor with an average relapse of 42 per cent (ranged 0-100 per cent). Overcompensation should, therefore, be undertaken with 2 mm added to the downgraft movement for bony relapse and 1 mm added to the downgraft movement for upper lip lengthening. The Tideman et al. method for advancement of the lesser maxillary segment is a very stable procedure (less than 8 per cent relapse). Semi-rigid fixation with plates, bone grafting and 'ramping' enhances stability; and freeway space assessment preoperatively is an important guide to relapse potential in the downgrafted cleft maxilla. All surgical prediction tracings should be done with the patient at the occlusal vertical dimension to prevent inadequate maxillary advancement and subsequent reverse overjet or excessive anterior incisor proclination developing with vertical relapse. PMID- 7993055 TI - The analysis of failure or success with oral and maxillofacial implants. AB - Prospective and retrospective studies on oral and maxillofacial osseointegrated implants have been performed and 'success' rates are reported to be very high. A critical analysis of the literature and anecdotal discussion with surgeons and prosthodontists alike, suggests that 'failures' occur considerably more frequently than is documented. This paper does not give a practical guide to the prevention or management of complications but it discusses the concepts of 'success' and 'failure' in implantology. Improvements in definitions, terminology and study design protocols are required together with research producing scientifically analytic and reproducible results rather than the present philosophy of the importance of the percentage of the commercial market share will allow an accurate analysis of the value and role of oral and maxillofacial implants. PMID- 7993056 TI - Reconstructive options for maxillary defects. AB - Reconstruction of the maxilla should aim to restore appearance, speech and occlusion. With modern reconstructive techniques and availability of an increasing variety of reliable tissue flaps, many of the traditional problems of treatment have been overcome. This paper reviews local and distant tissue flaps useful in rehabilitating an acquired maxillary defect of various dimensions. The local flaps discussed include flaps from the palate, cheek, tongue and the buccal fat pad. The distant flaps considered are the temporalis myofascial flap, pedicled cutaneous and myocutaneous flaps, and vascularized free flaps. Bony reconstruction of the maxilla with particular emphasis on restoring an anatomical alveolar ridge for occlusal rehabilitation by dental implants is presented. PMID- 7993058 TI - Giant cells in lesions of the oral region. AB - Multinucleated giant cells form by several different mechanisms in a variety of disease processes. They play a role in the host immune response to chronic infections, react to foreign materials and are an integral part of a number of bone disorders. A selection of lesions of the oral regions that contain giant cells will be presented. PMID- 7993057 TI - The mandibular infected buccal cyst--a reappraisal. AB - The mandibular infected buccal cyst was first described over ten years ago as a discrete pathological entity found only in children. The features of this lesion have been consistently described as a buccal location adjacent to erupting first molar teeth, a thick, hyperplastic non-keratinized epithelial lining, expansion of buccal cortex and associated infection. The paradental cyst had been described some years previously. This lesion was noted to have a similar non-specific hyperplastic non-keratinized epithelial lining but was described as being associated predominantly with third molar teeth in young adults. Recently investigators have called for the mandibular infected buccal cyst to be reclassified as a variant of the paradental cyst. In this paper, ten previously unreported cases of mandibular infected buccal cysts are presented and the evidence for their reclassification as paradental cysts is advanced. PMID- 7993059 TI - Update on contemporary management of oral maxillofacial infections. PMID- 7993060 TI - Risk factors associated with periodontal breakdown. AB - It is the intention of the authors to review previous reports of risk indicators for periodontal disease and correlate them according to their usefulness in the clinical arena. Cross-sectional as well as longitudinal studies have indicated possible risk factors associated with periodontal disease. A single aetiological factor cannot predict progression, but rather a multifactorial aetiology is needed for a prognosticatory diagnosis. Many contributing factors are noted. Age, smoking, diabetes, neutropenia, Down's syndrome, and the number of remaining teeth are some of those considered to be of influence. Acquired immune deficiency syndrome, race, socio-economic factors, frequency of dental visits, and previous attachment loss are host factors associated with periodontal disease. The purpose of this investigation is to review all possible risk factors in order to guide the clinician in determining which patients need conservative treatment or aggressive surgical therapy. PMID- 7993061 TI - External root resorption. AB - Root resorption is a pathological process initiated by specific clastic cells which remove the organic and mineral components of dental hard tissues. Clastic cell activity in teeth is associated with a number of factors which include biomechanical forces, mechanical, surgical and chemical trauma, endodontic micro oragnisms and their toxins, developmental defects, neoplasia, and hormonal disturbances. The therapeutic measures which can regulate clastic activity include endodontic treatment, the use of specific anticlastic agents such as Ledermix paste, non-specific necrobiotic agents such as calcium hydroxide and trichloracetic acid, surgery or root surface conditioners. Accurate diagnosis is essential to the correct application of therapy. While some resorptions are self limiting, others such as inflammatory root resorption require active and prompt endodontic preparation and medication to allow the control of clastic activity. One treatment regimen of invasive cervical and related conditions involves careful and accurate application of a chemical cauterizing agent, trichloracetic acid, followed by curettage and restoration. PMID- 7993062 TI - Images and communication: a radiological perspective. AB - Some advances in the technology of the digital acquisition of radiographic images are discussed. The role of teleradiology and other communication prospects within dentistry are proposed and some anticipated trends in the use of new technology suggested. The philosophical concept of Total Quality Management in dentistry is introduced. PMID- 7993063 TI - Minimal intervention dentistry. AB - The concepts of 'minimal intervention' or 'minimally invasive' restorative dentistry do not appear to be well understood or accepted. This paper attempts to clarify what is meant by these concepts, and to examine some of the difficulties preventing these concepts being fully implemented in general dental practice in Australia. Possible approaches to facilitating more widespread acceptance and adoption of these concepts are proposed. PMID- 7993064 TI - The role of guided tissue regeneration and guided bone regeneration. AB - The goal of periodontal therapy includes not only the halting of the progressive loss of connective tissue attachment but also the restitution of those parts of the supporting apparatus which have been destroyed. The cells which repopulate this area may originate from any number of the different tissue components of the periodontium: the dentogingival epithelium, the gingival connective tissue, the alveolar bone, and the periodontal ligament (PDL). The size and shape of the wound and the potential of the different types of tissues cells to migrate, determines the type of healing. Previous studies have revealed that root resorption was found to occur when granulation tissue derived from the gingival connective tissue or alveolar bone was proliferating into contact with the root surface, while re-epithelialization of the surface prevented both connective tissue attachment and root resorption. The only cells which appear to have the capacity to form a new attachment were cells originating from the PDL. Based on this knowledge of the biological behaviour of the different periodontal tissues during wound healing, the principle of Guided Tissue Regeneration (GTR) was introduced and tested. A membrane section was placed over the debrided root surface in such a way that all periodontal tissues except the PDL cells were prevented from reaching contact with the root. Healing resulted in extensive amounts of new connective tissue attachment, that is, the formation of new cementum with inserting collagen fibres. The objective was, and is, assessment of how predictably new attachment may form when treatment included GTR.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7993065 TI - The effect of cigarette smoking on the long-term success of guided tissue regeneration: a preliminary study. AB - Regenerative therapy has provided the clinician with an alternative to traditional procedures such as osseous surgery. However, there is a deficiency of data and research on long-term success of guided tissue regeneration (GTR). The purpose of this paper is to report the findings of a preliminary long-term clinical study of GTR in Class II furcation defects. In a private practice setting, 38 e-PTFE barrier membranes were placed in 38 periodontal Class II furcation lesions in patients diagnosed with chronic adult periodontitis (1 defect per patient). These patients were followed from 4 to 7 years. There were 21 maxillary Class II furcation defects and 17 mandibular Class II furcation defects. All patients had a non-contributory medical history; however, in retrospective examination, many of these patients smoked at least 10 cigarettes per day for at least 5 years. In this study, results after 4 to 7 years revealed a 58 per cent success rate and a 42 per cent failure rate: 80 per cent of the failures were in smokers. In this study, GTR in furcation defects was not as successful as previously reported in the literature from a clinical point of view and the success rate was significantly lower when a patient was a smoker. PMID- 7993066 TI - HIV--Australasian experience. Current status of HIV infection in Australasia. AB - The HIV/AIDS pandemic continues to evolve in a volatile and heterogeneous fashion and is now best described as a series of different but related epidemics, all posing their own particular problems. The response to the first decade of the epidemic in Australasia has been effective in a number of ways, but much remains to be done. The problems raised by recent cases of transmission of HIV in a health care setting have yet to be resolved. The characteristics of the local epidemic are increasingly divergent from the overseas models used to date, necessitating a flexible and creative approach tailored to the particular characteristics and needs of the local communities. PMID- 7993067 TI - A study on blood groups and serum proteins in Bengalee populations of Calcutta, India. AB - The genetic polymorphisms of two blood groups (A1A2B0, Rh-D) and two serum proteins (HP, TF) were investigated in five endogamous caste groups of Bengalee Hindu population living in Calcutta. The distribution of A1A2B0 and Rh-D blood groups in all the caste groups showed an oriental pattern with high B and Rh-D+ frequencies, while for the haptoglobins a very low frequency of HP*1 was seen in all the caste groups, except the Vaidya. For transferrin types the absolute predominancy of TF*C in all the caste groups was noted. PMID- 7993069 TI - Blood pressure distribution in a school age population of Quetta, Pakistan. AB - Standardized measurements of blood pressure, height and weight were obtained in 8 11 years old children, attending school in Quetta, Balochistan, Pakistan. The sample consisted of 427 individuals (219 boys and 208 girls). The blood pressure was measured by auscultatory method. To calculate the body mass index (BMI), the weight (kg) of each subject was divided by the square of the subject's height. Association between various variables and blood pressure was judged through correlation coefficient. The net and joint effect of selected variables on blood pressure variability was calculated using simple/multiple regression. The correlation coefficients with that of systolic blood pressure were 0.365, 0.427 and 0.341 whereas these were 0.397, 0.430 and 0.320 for diastolic blood pressure. Height had a regression coefficient of 0.475 mmHg/cm with systolic pressure and 0.419 mmHg/cm with diastolic blood pressure. Weight had a regression coefficient of 0.878 mmHg/kg and 0.717 mmHg/kg with systolic and diastolic pressure respectively whereas BMI had a regression coefficient of 2.35 mmHg/BMI unit with systolic pressure and 1.79 mmHg/BMI unit with diastolic blood pressure. PMID- 7993068 TI - Serum lipids and lipoproteins associations with ABO blood groups. AB - In the present study, total cholesterol, triglyceride, HDL-cholesterol and LDL cholesterol concentrations were evaluated in 393 Italian male blood donors aged from 20 to 59 years and the association between these variables and ABO blood groups was examined. Through multiple linear regression we found that the variance in serum variable concentrations was significantly influenced by variance in the other serum variables, while lipid and lipoprotein levels were not significantly influenced by age. In the population studied we did not find any association between total, HDL- and LDL-cholesterol and ABO blood groups while triglyceride levels were higher in individuals with B antigen (B + AB) than in subjects without this antigen. We think that environmental factors could be more important than genetic factors in the arousal of cardiovascular diseases. PMID- 7993070 TI - Mortality of the German linguistic isolates of the western Italian Alps (Walser). AB - For five localities of Western Alps (Val d'Aosta and Piemonte) inhabited by Walser populations (Gressoney-la-Trinite, Gressoney St. Jean, Issime, Macugnaga and Rima) the main features of mortality are described, namely raw death rate, seasonality of deaths, distribution of deaths according to age classes and infant mortality. Death rate is higher than the Italian average value; seasonality of deaths shows some statistically significative differences only in a few decades and does not reach a high significativity. Distribution in age classes shows a rather low mortality at lower ages (0 and 1-4 years) with small changes between the two halves of the 20th century. An exception is constituted by Macugnaga, where an elevated mortality at lower age classes is present in both halves of the century, though higher in the first one. The picture can be considered as not typical of Walser populations. Infant mortality shows great variations in the investigated isolates, but an explication today is impossible. The degree of illiteracy, one of the causes of infant mortality, is rather elevated only at Macugnaga (until 1931). A comparison is made with other German linguistic islands studied so far by one of the two authors (G.M.). PMID- 7993071 TI - [Comparative biometric studies of school children from Kenya and Braunschweig]. AB - Constitution and growth biology of 6 to 7 years old children from a European city ("Braunschweiger Langsschnitt") and a country with rather original habits (extreme rural area of Kenya, "Abaluya"--administrative name of Bantuid tribes from W-Kenya--out of the region of Idakho and Tiriki, elevated in spring 1990) were comparatively studied. To achieve comparability in physique and body height, the elevated data were "allometrically standardized". The statistical parameters and the results of correlation statistics were shown by comparing the two groups of children. This paper is thought to be the first attempt of a more extensive study in which further more comparative data from other age groups of children and different ecological factors as climate or nutrition should be involved in the analysis. At least the knowledge of standardized data is a cogent assumption to judge about constitution, typology and health of populations. PMID- 7993072 TI - Inhibition of human adenoviruses by 1-(2'-hydroxy-5'-methoxybenzylidene)amino-3 hydroxyguanidine tosylate. AB - Antiviral activities of four Schiff bases of aminohydroxyguanidine, designated ML1, ML4, ATL14 and LK11, were tested against human adenovirus types 5 and 8 (Ad5 and Ad8) in A549 cells by plaque reduction and virus yield reduction methods. Compound (ML1 1-(2'-hydroxy-5'-methoxybenzylidene)amino-3-hydroxyguanidine tosylate gave the best therapeutic indices (TC50/IC50) of 27.2 and 17.8 for Ad5 and Ad8, respectively. Pretreatment of cells with ML1 did not affect the adsorption nor the penetration of virus. Ultrastructure studies showed that only the drug treated infected cells had unidentified irregular shaped electron dense structures that might be drug altered viral macromolecules that were not assembled into complete infectious virus particles. Since these compounds have metal chelating properties, their antiviral activity may involve the early IA (EIA) gene which encodes a viral protein of 289 amino acid which has a zinc finger moiety that is required for its transactivation activity. PMID- 7993073 TI - Bicyclic imidazo derivatives, a new class of highly selective inhibitors for the human immunodeficiency virus type 1. AB - In the search for new antiviral agents against human immunodeficiency virus, different members of two imidazoheterocycle families (imidazothiazoles, imidazopyridines) have been found to display potent inhibitory effects on the replication of HIV-1. Three of these derivatives, which show significant anti-HIV 1 activity, have been chosen for further studies. The analysis of these compounds and their comparison to AZT and TIBO revealed that these bicyclic imidazo derivatives represent a class of highly specific inhibitors of HIV-1, but not of HIV-2 or simian immunodeficiency virus (SIV). Their inhibition of HIV-1 is mediated through interaction with the reverse transcriptase (RT). The mechanism of action of these bicyclic imidazo derivatives may be similar to that of the other non-nucleoside RT inhibitors (NNRTIs). PMID- 7993074 TI - Stereoelectronic properties of five anti-HSV-1 2'-deoxynucleosides analogues with heterocyclic substituents in the 5-position: a comparison with BVDU. AB - Structural and electronic characteristics of 5-(5-chlorothien-2-yl)-2' deoxyuridine (I), 5-(furan-2-yl)-2'-deoxyuridine (II), 5-(5-bromofuran-2-yl)-2' deoxyuridine (III), 5-(3-bromoisoxazol-5-yl)-2'-deoxyuridine (V) and 5-(isoxazol 5-yl)-2'-deoxyuridine (IV) have been determined and compared to the BVDU (VI) characteristics in order to explain their respective affinity for the herpes simplex virus type 1 thymidine kinase (TK). Molecular structure of 5-(5 chlorothien-2-yl)-2'-deoxyuridine has been obtained using single crystal X-ray crystallography. Electrostatic potential maps, energy and topology of frontier orbitals were computed at the ab initio MO STO-3G and STO-3G level. These studies reveal that the electrostatic potential energy maps are clearly dependent on the affinity of the compound for the enzyme. PMID- 7993075 TI - Inhibition of human immunodeficiency virus by N-methylisatin-beta 4':4' diethylthiosemicarbazone and N-allylisatin-beta-4':4'-diallythiosemicarbazone. AB - N-methylisatin-beta 4':4'-diethylthiosemicarbazone(M-IBDET) and N-allylisatin beta-4':4'-diallylthiosemicarbazone(A-IBDAT ) inhibit the production of Human Immunodeficiency virus (HIV). Virus inhibition was related to the thiosemicarbazone derivative (TSCD) concentrations and time of treatment. Inhibition of HIV production was confirmed by various parameters of virus assay employing reverse transcriptase activity, plaque forming units (PFU) and levels of viral structural proteins. Effective antiviral TSCD concentrations ranged from 0.17 microM to 2.04 microM for M-IBDET, and from 1.45 microM to 17.4 microM for A IBDAT. Treatment of the chronic HIV-infected cells for 48 h with 0.34 microM M IBDET or 2.9 microM A-IBDAT caused about 50% inhibition in as virus yield ED50 as assayed by the PFU method. Almost 2 logs of virus infectivity (PFU) was suppressed after 48 h of treatment with 17.4 microM A-IBDAT. Therapeutic index values of 20 and 30 were found for M-IBDET and A-IBDAT, respectively. A significant selective inhibition of HIV structural protein synthesis was shown by both M-IBDET and A-IBDAT. PMID- 7993076 TI - Synthesis of 5-[1-hydroxy (or methoxy)-2,2-dihaloethyl]-2'- deoxyuridines with antiviral and cytotoxic activity. AB - The 5-[1-hydroxy (or methoxy)-2,2-dihaloethyl]-2'-deoxyuridines (3-12, Cl, Br and/or I) were synthesized by the addition of HOX or CH3OX (X = Cl, Br, I) to the vinyl substituent of the respective (E)-5-(2-halovinyl)-2'-deoxyuridines (1a-c). In vitro antiviral (HSV-1, HSV-2, HCMV, VZV, EBV) and cytotoxic (L1210) activities were determined. The 5-(1-hydroxy-2,2-dihaloethyl) series were generally more active than the 5-(1-methoxy-2,2-dihaloethyl) series against HSV 1, HSV-2, VZV and EBV. Anti-HSV-1 activity was dependent upon the steric orientation and/or hydrophobic properties of the halogen atom(s), with CH(OH)CHBr(I) and -CH(OH)CHBr2 C-5 substituents providing the most potent activity. 5-(1-Hydroxy-2-bromo-2-iodoethyl)-2'-deoxyuridine (6), which exhibited the most potent anti-HSV-1 activity, was 12-fold less active than acyclovir. In contrast, the halogen atom(s) were not determinants of anti-VZV activity, where the approximately equipotent 5-(1-hydroxy-2,2-dihaloethyl) compounds (3, 4, 5, 6) exhibited anti-VZV activity comparable to that of acyclovir. All of the 5-(1 hydroxy (or methoxy)-2,2-dihaloethyl) analogs (3-12) were inactive against HCMV. The 5-(1-hydroxy-2-chloro-2-iodoethyl) compound (4) was an active cytotoxic agent as determined in the in vitro L1210 screen. The compounds 3-12 were non-toxic to uninfected host cells. The inhibitory effect on cell proliferation diminished upon replacement of the 5-(1-hydroxy-2,2-dihaloethyl) substituents of 3-6 with the corresponding 5-(1-methoxy-2,2-dihaloethyl) substituents (7-12). PMID- 7993077 TI - Use of a flavivirus RNA-dependent RNA polymerase assay to investigate the antiviral activity of selected compounds. AB - We have developed an assay using flavivirus RNA-dependent RNA polymerase to test the inhibitory activity of potential antiviral agents. The effects of antiviral agents on RNA synthesis were examined in this assay using extracts of Vero cells infected with dengue virus type 2 or Kunjin virus. Several different classes of known polymerase inhibitors were tested. The synthesis of double-stranded replicative form RNA was inhibited in a dose-dependent fashion in the presence of the polyoxometalate HPA-23 [(NH4)18(NaW21Sb9O86)17].14 H2O and several structurally related compounds. PMID- 7993078 TI - Inhibition of the growth of influenza viruses in vitro by 4-guanidino-2,4-dideoxy N-acetylneuraminic acid. AB - The sialidase inhibitor 4-guanidino-2,4-dideoxy-2,3-dehydro-N- acetylneuraminic acid was tested for growth inhibitory effects against a panel of avian influenza A viruses encompassing all nine neuraminidase subtypes. Growth in tissue culture of viruses from each subtype was inhibited by this compound at concentrations within a range previously found effective against human N1 and N2 viruses. This compound may prove a selective agent for the treatment (and prevention) of influenza virus infections. PMID- 7993080 TI - Engineering of Escherichia coli central metabolism for aromatic metabolite production with near theoretical yield. AB - Escherichia coli and many other microorganisms synthesize aromatic amino acids through the condensation reaction between phosphoenolpyruvate (PEP) and erythrose 4-phosphate to form 3-deoxy-D-arabinoheptulosonate 7-phosphate (DAHP). It has been shown that overexpression of transketolase increases the production of DAHP in an aroB mutant strain (unable to further metabolize DAHP) with elevated DAHP synthase. However, the yield (percent conversion) of DAHP from glucose is still low. Stoichiometric analysis shows that many enzymes compete for intracellular PEP. In particular, the phosphotransferase system, responsible for glucose transport in E. coli, uses PEP as a phosphate donor and converts it to pyruvate, which is less likely to recycle back to PEP. This stoichiometric limitation greatly reduces the yield of aromatic metabolites. To relieve this limitation, we overexpressed PEP synthase in the presence of glucose and showed that it increased the final concentration and the yield of DAHP by almost twofold, to a near theoretical maximum. The PEP synthase effect is not observed without overproduced transketolase, suggesting that erythrose 4-phosphate is the first limiting metabolite. This result demonstrates the utility of pathway analysis and the limitation of central metabolites in the high-level overproduction of desired metabolites. PMID- 7993079 TI - Efficacy of ganciclovir in combination with zidovudine against cytomegalovirus in vitro and in vivo. Freitas, V.R., Fraser-Smith, E.B., Chiu, S., Michelson, S. and Schatzman, R.C. (1993) Antiviral Res. 21, 301-315. PMID- 7993081 TI - Evidence for microbial iron reduction in a landfill leachate-polluted aquifer (Vejen, Denmark). AB - Aquifer sediment samples obtained from the anaerobic part of a landfill leachate plume in Vejen, Denmark, were suspended in groundwater or in an artificial medium and incubated. The strictly anaerobic suspensions were tested for reduction of ferric iron [Fe(III)] oxides, which was measured as an increase in the concentration of dissolved Fe(II). Iron reduction did not occur when the medium was inoculated with inactive sediment and when the organisms in the inoculated medium were killed by formaldehyde, by chloroform, or by pasteurization, whereas the level of iron reduction was significant when living bacteria were present. Mixed cultures were obtained from the sediment samples, and differences in apparent iron reduction rates among the different cultures were maintained during several transfers. In addition, iron reduction was observed in unamended incubation mixtures containing whole sediment and groundwater. Synthetic amorphous Fe(III) oxides, as well as naturally occurring sediment-bound Fe(III) oxides, could be reduced by the cultures. Together, our results provide evidence that iron-reducing bacteria are present and microbial iron reduction occurs in the polluted aquifer sediments which we studied. PMID- 7993082 TI - Analysis of the raw starch-binding domain by mutation of a glucoamylase from Aspergillus awamori var. kawachi expressed in Saccharomyces cerevisiae. AB - Carboxy-terminal deletions were introduced into the raw starch-binding domain (A 515 to R-615) encoded by the gene for glucoamylase I (GAI) from Aspergillus awamori var. kawachi. Genes coding for proteins designated GA596 (A-1 to E-596), GA570 (A-1 to A-570), and GA559 (A-1 to N-559) were constructed and resulted in truncated proteins. All of the mutant genes were expressed heterologously in Saccharomyces cerevisiae. GA596 adsorbed to raw starch and digested it. GA570 and GA559 did not adsorb to raw starch or to an alpha-cyclodextrin-Sepharose CL-4B gel under our experimental conditions. However, GA570 was able to digest raw starch, and the digestion of raw starch by GA570 was inhibited by beta cyclodextrin. Residue Trp-562 of GAI, which was suggested previously to contribute to formation of an inclusion complex with raw starch, was replaced by Leu (GAW562L), Phe (GAW562F), and Gly (GAW562G). GAW562L and GAW562F adsorbed to raw starch and an alpha-cyclodextrin gel, but GAW562G did not. Although GAW562L digested raw starch to the same extent as wild-type GAI (designated GAY), GAW562F and GAW562G exhibited less ability to digest raw starch. On the basis of our results, it appears that the sequence around Trp-562, PL(W-562)YVTVTLPA, is the minimal sequence necessary for digestion of raw starch and that hydrophobic residue Trp-562 contributes to formation of an inclusion complex. The sequence near Trp-589, which has abundant hydrogen bond-forming residues and the charged amino acid residues needed for stable adsorption to raw starch, probably assists in the formation of the inclusion complex. PMID- 7993083 TI - Metabolism of benz[a]anthracene by the filamentous fungus Cunninghamella elegans. AB - The metabolism of the carcinogen benz[a]anthracene (BA), a tetracyclic aromatic hydrocarbon, by Cunninghamella elegans was investigated. C. elegans grown on Sabouraud dextrose broth transformed [14C]BA to labeled BA trans-8,9-dihydrodiol (90%), BA trans-10,11-dihydrodiol (6%), and BA trans-3,4-dihydrodiol (4%), but not to BA trans-5,6-dihydrodiol. These metabolites were separated by thin-layer chromatography and reversed-phase high-performance liquid chromatography and were identified by UV and mass spectral techniques. A BA tetraol, 8 beta,9 alpha,10 alpha,11 beta-tetrahydroxy-8 alpha, 9 beta,10 beta,11 alpha-tetrahydro-BA, was also identified as a metabolite and may have arisen as an additional oxidation product of either BA 8,9- or 10,11-dihydrodiol. This is the first study in which a biologically produced BA tetraol has been identified. Our results suggest that the transformation of BA to trans-dihydrodiols by C. elegans is similar to the transformation of BA found in mammals, except that BA 5,6-dihydrodiol is not produced. PMID- 7993084 TI - Acetate metabolism by Escherichia coli in high-cell-density fermentation. AB - Little is known about the cellular physiology of Escherichia coli at high cell densities (e.g., greater than 50 g [dry cell weight] per liter), particularly in relation to the cellular response to different growth conditions. E. coli W3100 cultures were grown under identical physical and nutritional conditions, by using a computer-controlled fermentation system which maintains the glucose concentration at 0.5 g/liter, to high cell densities at pH values of 6.0, 6.5, 7.0, and 7.5. The data suggest a relationship between the pH of the environment and the amount of acetate excreted by the organism during growth. At pH values of 6.0 and 6.5, the acetate reached a concentration of 6 g/liter, whereas at pH 7.5, the acetate reached a concentration of 12 g/liter. Furthermore, at pH values of 6.0 to 7.0, the E. coli culture undergoes a dramatic metabolic switch in which oxygen and glucose consumption and CO2 evolution all temporarily decreased by 50 to 80%, with a concomitant initiation of acetate utilization. After a 30-min pause in which approximately 50% of the available acetate is consumed, the culture recovers and resumes consuming glucose and oxygen and producing acetate and CO2 at preswitch levels. During the switch period, the specific activity of isocitrate lyase typically increases approximately fourfold. PMID- 7993085 TI - Plant and algal interference in bacterial beta-D-galactosidase and beta-D glucuronidase assays. AB - Several commonly occurring freshwater and marine plants and algae were screened for beta-D-galactosidase and beta-D-glucuronidase activities by using a 60-min enzyme assay based on the hydrolysis by these enzymes of 4-methylumbelliferyl beta-D-galactoside and 4-methylumbelliferyl- beta-glucuronide, respectively. All freshwater plant extracts tested showed beta-D-galactosidase activity several at relatively high levels, and a number also showed beta-D-glucuronidase activity. A number of the macroalgae showed no activity of either enzyme, but those showing beta-D-galactosidase activity also showed beta-D-glucuronidase activity. The majority of microalgae showed some beta-D-galactosidase activity, but few showed beta-D-glucuronidase activity. Further studies, using the commercial Colilert test and the marine water formulation of Colilert, revealed that 2 of 11 of the microalgal species and several of the plant extracts tested caused positive reactions. It was concluded that several plant extracts and algae could significantly interfere with the detection of coliform bacteria and Escherichia coli with the use of rapid assays, on the basis of their production of beta-D galactosidase and beta-D-glucuronidase, respectively. The significance of the plant and algal interferences in tests such as Colilert is dependent on the levels of enzymes released under natural conditions, the dilution which they may undergo, and the numbers of algal cells present. This also applies to interferences in rapid enzyme assays.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7993086 TI - Construction of phoE-caa, a novel PCR- and immunologically detectable marker gene for Pseudomonas putida. AB - In this paper we describe the construction and use in Pseudomonas putida WCS358 of phoE-caa, a novel hybrid marker gene, which allows monitoring both at the protein level by immunological methods and at the DNA level by PCR. The marker is based on the Escherichia coli outer membrane protein gene phoE and 75 bp of E. coli caa, which encode a nonbacteriocinic fragment of colicin A. This fragment contains an epitope which is recognized by monoclonal antibody (MAb) 1C11. As the epitope is contained in one of the cell surface-exposed loops of PhoE, whole cells of bacteria expressing the protein can be detected by using the MAb. The marker gene contains only E. coli sequences not coding for toxins and therefore can be considered environmentally safe. The hybrid PhoE-ColA protein was expressed in E. coli under conditions of phosphate starvation, and single cells could be detected by immunofluorescence microscopy with MAb 1C11. Using a wide host-range vector the phoE-caa gene was introduced into P. putida WCS358. The gene appeared to be expressed under phosphate limitation in this species, and the gene product was present in the membrane fraction and reacted with MAb 1C11. The hybrid PhoE-ColA protein could be detected on whole cells of WCS358 mutant strains lacking (part of) the O-antigen of the lipopolysaccharide but not on wild type WCS358 cells, unless these cells had previously been washed with 10 mM EDTA. In addition to immunodetection, the phoE-caa marker gene could be specifically detected by PCR with one primer directed to a part of the phoE sequence and a second primer that annealed to the caa insert. PMID- 7993087 TI - Cloning and sequencing of a serine proteinase gene from a thermophilic Bacillus species and its expression in Escherichia coli. AB - The gene for a serine proteinase from a thermophilic Bacillus species was identified by PCR amplification, and the complete gene was cloned after identification and isolation of suitably sized restriction fragments from Southern blots by using the PCR product as a probe. Two additional, distinct PCR products, which were shown to have been derived from other serine proteinase genes present in the thermophilic Bacillus species, were also obtained. Sequence analysis showed an open reading frame of 1,206 bp, coding for a polypeptide of 401 amino acids. The polypeptide was determined to be an extracellular serine proteinase with a signal sequence and prosequence. The mature proteinase possessed homology to the subtilisin-like serine proteinases from a number of Bacillus species and had 61% homology to thermitase, a serine proteinase from Thermoactinomyces vulgaris. The gene was expressed in Escherichia coli in the expression vector pJLA602 and as a fusion with the alpha-peptide of the lacZ gene in the cloning vector pGEM5. A recombinant proteinase from the lacZ fusion plasmid was used to determine some characteristics of the enzyme, which showed a pH optimum of 8.5, a temperature optimum of 75 degrees C, and thermostabilities ranging from a half-life of 12.2 min at 90 degrees C to a half-life of 40.3 h at 75 degrees C. The enzyme was bound to a bacitracin column, and this method provided a simple, one-step method for producing the proteinase, purified to near homogeneity. PMID- 7993088 TI - A novel strictly anaerobic recovery and enrichment system incorporating lithium for detection of heat-injured Listeria monocytogenes in pasteurized milk containing background microflora. AB - Heat-injured cells of Listeria monocytogenes were recovered from heated raw milk containing noninjured Enterococcus faecium by combining a simple method for obtaining strict anaerobiosis with a novel enrichment broth, Penn State University broth (PSU broth). Strictly anaerobic conditions were rapidly achieved by adding 0.5 g of filter-sterilized cysteine per liter to PSU broth and then purging the preparation with N2 gas. Little resuscitation or growth occurred in strictly anaerobic PSU broth without lithium chloride because of overgrowth by E. faecium. The growth of E. faecium decreased dramatically with increasing LiCl concentration; LiCl concentrations of 8 and 10 g/liter were completely bacteriostatic. The mechanism of inhibition by LiCl appeared to involve competition with the divalent cations Ca2+ and Mg2+. Heat-injured L. monocytogenes consistently recovered and grew rapidly in strictly anaerobic PSU broth containing 4, 6, or 7 g of LiCl per liter. The use of strictly anaerobic PSU broth containing 7 g of LiCl per liter permitted detection of severely heat injured L. monocytogenes in one simple recovery-enrichment step by eliminating oxygen toxicity and inhibiting the growth of background microflora, without preventing the resuscitation and subsequent growth of heat-injured L. monocytogenes. L. monocytogenes heated in raw milk at 62.8 degrees C for 10, 15, and 20 min could be consistently recovered from strictly anaerobic PSU broth enrichment cultures at 30 degrees C after 48, 96, and 144 h, respectively, and hence, use of PSU broth may result in better recovery of both injured and noninjured cells from foods than currently used U.S. Department of Agriculture and Food and Drug Administration preenrichment procedures. PMID- 7993089 TI - Destruction of gram-negative food-borne pathogens by high pH involves disruption of the cytoplasmic membrane. AB - High pH has been shown to rapidly destroy gram-negative food-borne pathogens; however, the mechanism of destruction has not yet been elucidated. Escherichia coli O157:H7, Salmonella enteritidis ATCC 13706, and Listeria monocytogenes F5069 were suspended in NaHCO3-NaOH buffer solutions at pH 9, 10, 11, or 12 to give a final cell concentration of approximately 5.2 x 10(8) CFU/ml and then held at 37 or 45 degrees C. At 0, 5, 10, and 15 min the suspensions were sterilely filtered and each filtrate was analyzed for material with A260. Viability of the cell suspensions was evaluated by enumeration on nonselective and selective agars. Cell morphology was evaluated by scanning electron microscopy and transmission electron microscopy. A260 increased dramatically with pH and temperature for both E. coli and S. enteritidis; however, with L. monocytogenes material with A260 was not detected at any of the pHs tested. At pH 12, numbers of E. coli and S. enteritidis decreased at least 8 logs within 15 s, whereas L. monocytogenes decreased by only 1 log in 10 min. There was a very strong correlation between the initial rate of release of material with A260 and death rate of the gram negative pathogens (r = 0.997). At pH 12, gram-negative test cells appeared collapsed and showed evidence of lysis while gram-positive L. monocytogenes did not, when observed by scanning and transmission electron microscopy. It was concluded that destruction of gram-negative food-borne pathogens by high pH involves disruption of the cytoplasmic membrane. PMID- 7993090 TI - Molecular characterization of races and vegetative compatibility groups in Fusarium oxysporum f. sp. vasinfectum. AB - Restriction fragment length polymorphism (RFLP) and vegetative compatibility analyses were undertaken to assess genetic relationships among 52 isolates of Fusarium oxysporum f. sp. vasinfectum of worldwide origin and representing race A, 3, or 4 on cotton plants. Ten distinct vegetative compatibility groups (VCGs) were obtained, and isolates belonging to distinct races were never in the same VCG. Race A isolates were separated into eight VCGs, whereas isolates of race 3 were classified into a single VCG (0113), as were those of race 4 (0114). Ribosomal and mitochondrial DNA (rDNA and mtDNA) RFLPs separated four rDNA haplotypes and seven mtDNA haplotypes. Race A isolates displayed the most polymorphism, with three rDNA haplotypes and four mtDNA haplotypes; race 4 isolates formed a single rDNA group but exhibited three mtDNA haplotypes, while race 3 isolates had unique rDNA and mtDNA haplotypes. Two mtDNA molecules with distinct sizes were identified; the first (45-kb mtDNA) was found in all race A isolates and seven race 4 isolates, and the second (55-kb mtDNA) was found in all race 3 isolates and in two isolates of race 4. These two mtDNA molecules were closely related to mtDNAs of F. oxysporum isolates belonging to other formae speciales (conglutinans, lycopersici, matthioli, and raphani). Isolates within a VCG shared the same rDNA and mtDNA haplotypes, with the exception of VCG0114, in which three distinct mtDNA haplotypes were observed. Genetic relationships among isolates inferred from rDNA or mtDNA site restriction data were different, and there was not a strict correlation between race and RFLPs.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7993091 TI - Initial reactions in the anaerobic oxidation of toluene and m-xylene by denitrifying bacteria. AB - Pseudomonas sp. strain T and Pseudomonas sp. strain K172 grow with toluene under denitrifying conditions. We demonstrated that anaerobic degradation of toluene was initiated by direct oxidation of the methyl group. Benzaldehyde and benzoate accumulated sequentially after toluene was added when cell suspensions were incubated at 5 degrees C. Strain T also grows anaerobically with m-xylene, and we demonstrated that degradation was initiated by oxidation of one methyl group. In cell suspensions incubated at 5 degrees C 3-methylbenzaldehyde and 3 methylbenzoate accumulated after m-xylene was added. Toluene- or m-xylene-grown strain T cells were induced to the same extent for oxidation of both hydrocarbons. In addition, the methyl group-oxidizing enzyme system of strain T also catalyzed the oxidation of each isomer of the chloro- and fluorotoluenes to the corresponding halogenated benzoate derivatives. In contrast, strain K172 only oxidized 4-fluorotoluene to 4-fluorobenzoate, probably because of the narrow substrate specificity of the methyl group-oxidizing enzymatic system. During anaerobic growth with toluene strains T and K172 produced two transformation products, benzylsuccinate and benzylfumarate. About 0.5% of the toluene carbon was converted to these products. PMID- 7993092 TI - Frequency of horizontal gene transfer of a large catabolic plasmid (pJP4) in soil. AB - Limited work has been done to assess the bioremediation potential of transfer of plasmid-borne degradative genes from introduced to indigenous organisms in the environment. Here we demonstrate the transfer by conjugation of the catabolic plasmid pJP4, using a model system with donor and recipient organisms. The donor organism was Alcaligenes eutrophus JMP134 and the recipient organism was Variovorax paradoxus isolated from a toxic waste site. Plasmid pJP4 contains genes for mercury resistance and 2,4-dichlorophenoxyacetic (2,4-D) acid degradation. A transfer frequency of approximately 1/10(3) donor and recipient cells (parent cells) was observed on solid agar media, decreasing to 1/10(5) parent cells in sterile soil and finally 1/10(6) parent cells in 2,4-D-amended, nonsterile soil. Presumptive transconjugants were confirmed to be resistant to Hg, to be capable of degrading 2,4-D, and to contain a plasmid of size comparable to that of pJP4. In addition, we confirmed the transfer through PCR amplifications of the tfdB gene. Although transfer of pJP4 did occur at a high frequency in pure culture, the rate was significantly decreased by the introduction of abiotic (sterile soil) and biotic (nonsterile soil) stresses. An evaluation of the data from this model system implies that the reliance on plasmid transfer from a donor organism as a remediative strategy has limited potential. PMID- 7993093 TI - Characterization of Acinetobacter type strains and isolates obtained from wastewater treatment plants by PCR fingerprinting. AB - Acinetobacter type strains and isolates from wastewater treatment plants were differentiated by PCR fingerprinting. On the first level, PCR fingerprinting with two tRNA-gene specific primers (T5B and T3A) was used for the identification of species (genospecies 1 to 17). On the second level, a single arbitrary primer (DAF 4) was employed for strain differentiation. Upon comparison of Acinetobacter type strains with 28 sewage sludge isolates, 2 could be classified as belonging to A. johnsonii, 8 isolates could be classified as A. lwoffii, 8 could be classified as A. baumannii, and 9 isolates were very closely related to the Acinetobacter species A. junii; only 1 isolate could not be classified as one of the Acinetobacter type strains. The PCR fingerprinting method was found to be a reproducible and fast method for differentiation and identification of Acinetobacter isolates. Because of some resulting discrepancies compared with previously described identification schemes, e.g., DNA-DNA hybridization methods, the original identification experiments should be repeated and the results should be reassessed. PMID- 7993095 TI - Sensitive and specific detection of Xanthomonas campestris pv. pelargonii with DNA primers and probes identified by random amplified polymorphic DNA analysis. AB - The random amplified polymorphic DNA method was used to distinguish strains of Xanthomonas campestris pv. pelargonii from 21 other Xanthomonas species and/or pathovars. Among the 42 arbitrarily chosen primers evaluated, 3 were found to reveal diagnostic polymorphisms when purified DNAs from compared strains were amplified by the PCR. The three primers revealed DNA amplification patterns which were conserved among all 53 strains tested of X. campestris pv. pelargonii isolated from various locations worldwide. The distinctive X. compestris pv. pelargonii patterns were clearly different from those obtained with any of 46 other Xanthomonas strains tested. An amplified 1.2-kb DNA fragment, apparently unique to X. campestris pv. pelargonii by these random amplified polymorphic DNA tests, was cloned and evaluated as a diagnostic DNA probe. It hybridized with total DNA from all 53 X. campestris pv. pelargonii strains tested and not with any of the 46 other Xanthomonas strains tested. The DNA sequence of the terminal ends of this 1.2-kb fragment was obtained and used to design a pair of 18-mer oligonucleotide primers specific for X. campestris pv. pelargonii. The custom synthesized primers amplified the same 1.2-kb DNA fragment from all 53 X. campestris pv. pelargonii strains tested and failed to amplify DNA from any of the 46 other Xanthomonas strains tested. DNA isolated from saprophytes associated with the geranium plant also did not produce amplified DNA with these primers. The sensitivity of the PCR assay using the custom-synthesized primers was between 10 and 50 cells.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7993094 TI - Structural and functional analysis of the nor-1 gene involved in the biosynthesis of aflatoxins by Aspergillus parasiticus. AB - The nor-1 gene was cloned previously by complementation of a mutation (nor-1) in Aspergillus parasiticus SU-1 which blocked aflatoxin B1 biosynthesis, resulting in the accumulation of norsolorinic acid (NA). In this study, the nucleotide sequences of the cDNA and genomic DNA clones encompassing the coding region of the nor-1 gene were determined. The transcription initiation and polyadenylation sites of nor-1 were located by primer extension and RNase protection analyses and by comparison of the nucleotide sequences of the nor-1 genomic and cDNA clones. A plasmid, pNA51-82, was created for one-step disruption of the nor-1 gene by inserting a functional copy of the nitrate reductase (niaD) gene from A. parasiticus into the coding region of the nor-1 gene. Transformation of A. parasiticus NR-3 (niaD Afl+) with pNA51-82 resulted in niaD+ transformants that accumulated NA and produced reduced levels of aflatoxin as determined by thin layer chromatography and enzyme-linked immunosorbent assay analyses of extracts from mycelia and the growth medium. Southern analysis of genomic DNA isolated from the NA-accumulating transformants indicated that the wild-type nor-1 gene in the chromosome had been replaced by the nonfunctional allele carried on pNA51-82. This recombinational inactivation event provides direct evidence that the nor-1 gene is functionally involved in aflatoxin biosynthesis. Comparison of the predicted nor-1 amino acid sequence with sequences in the GenBank and EMBL databases suggested that the protein is a member of the family of short-chain alcohol dehydrogenases, consistent with its proposed function as a keto reductase. PMID- 7993096 TI - Metabolism of chlorofluorocarbons and polybrominated compounds by Pseudomonas putida G786(pHG-2) via an engineered metabolic pathway. AB - The recombinant bacterium Pseudomonas putida G786(pHG-2) metabolizes pentachloroethane to glyoxylate and carbon dioxide, using cytochrome P-450CAM and toluene dioxygenase to catalyze consecutive reductive and oxidative dehalogenation reactions (L.P. Wackett, M.J. Sadowsky, L.N. Newman, H.-G. Hur, and S. Li, Nature [London] 368:627-629, 1994). The present study investigated metabolism of brominated and chlorofluorocarbon compounds by the recombinant strain. Under anaerobic conditions, P. putida G786(pHG-2) reduced 1,1,2,2 tetrabromoethane, 1,2-dibromo-1,2-dichloroethane, and 1,1,1,2-tetrachloro-2,2 difluoroethane to products bearing fewer halogen substituents. Under aerobic conditions, P. putida G786(pHG-2) oxidized cis- and trans-1,2-dibromoethenes, 1,1 dichloro-2,2-difluoroethene, and 1,2-dichloro-1-fluoroethene. Several compounds were metabolized by sequential reductive and oxidative reactions via the constructed metabolic pathway. For example, 1,1,2,2-tetrabromoethane was reduced by cytochrome P-450CAM to 1,2-dibromoethenes, which were subsequently oxidized by toluene dioxygenase. The same pathway metabolized 1,1,1,2-tetrachloro-2,2 difluoroethane to oxalic acid as one of the final products. The results obtained in this study indicate that P. putida G786(pHG-2) metabolizes polyfluorinated, chlorinated, and brominated compounds and further demonstrates the value of using a knowledge of catabolic enzymes and recombinant DNA technology to construct useful metabolic pathways. PMID- 7993097 TI - Isolation, characterization, and expression of a second beta-tubulin-encoding gene from Colletotrichum gloeosporioides f. sp. aeschynomene. AB - Colletotrichum gloeosporioides f. sp. aeschynomene is a fungal plant pathogen of Aeschynomene virginica. A beta-tubulin-encoding gene (TUB2) from this pathogen was cloned and sequenced. The deduced amino acid sequence of TUB2 had a high degree of homology to other fungal beta-tubulins. A portion of TUB2 from a benomyl-resistant C. gloeosporioides f. sp. aeschynomene mutant was also cloned and sequenced. A point mutation resulting in a glutamic acid-to-lysine substitution at amino acid 198 likely confers benomyl resistance. The mutation is relevant for use as a selectable marker in developing a gene transfer system in C. gloeosporioides f. sp. aeschynomene. Northern (RNA) hybridizations with C. gloeosporioides f. sp. aeschynomene TUB2 and another C. gloeosporioides f. sp. aeschynomene beta-tubulin-encoding gene (TUB1) as probes showed differential expression of these genes in different cell types. PMID- 7993098 TI - Fungal production of volatiles during growth on fiberglass. AB - Acoustic and thermal fiberglass insulation materials used in heating, ventilation, and air-conditioning systems were colonized with fungi in laboratory chambers. The mixed fungal population, principally Aspergillus versicolor, Acremonium obclavatum, and Cladosporium herbarum, produced odoriferous volatiles, including 2-ethyl hexanol, cyclohexane, and benzene. These volatiles may be related to poor indoor air quality and the sick building syndrome. PMID- 7993099 TI - Correlation of bioenergetic parameters with cell death in Listeria monocytogenes cells exposed to nisin. AB - In Listeria monocytogenes, nisin induced ATP efflux, reduced the intracellular ATP concentration within 1 min, and dissipated the proton motive force within 2 min. Efflux accounted for only 20% of the ATP depletion, suggesting that ATP hydrolysis also occurred. ATP efflux depended on nisin concentration and followed saturation kinetics. These results suggest that nisin breaches the membrane permeability barrier in a manner more consistent with pore formation than with a nonspecific detergent-like membrane destabilization. PMID- 7993100 TI - Construction of Agrobacterium strains by electroporation of genomic DNA and its utility in analysis of chromosomal virulence mutations. AB - We have extended the technique of electroporation as a genetic tool for manipulating the Agrobacterium tumefaciens chromosome. We used this technique to introduce chromosomal DNA into recipient A. tumefaciens strains by electroporation and constructed isogenic chvE mutants that share the same chromosomal background but differ in their types of pTi (octopine or nopaline). Both nopaline and octopine pTi-carrying chvE mutants were deficient in vir regulon induction and exhibited similar reductions in host range. PMID- 7993101 TI - Expression of mosquitocidal toxin genes in a gas-vacuolated strain of Ancylobacter aquaticus. AB - A series of plasmids bearing the binary toxin genes of Bacillus sphaericus 2297 or 2317.3, the 100-kDa toxin gene of B. sphaericus SSII-1, or the 130-kDa (cryIVB) toxin gene of Bacillus thuringiensis subsp. israelensis were constructed and introduced into Ancylobacter aquaticus by electroporation. The transformed A. aquaticus cells exhibited significant toxicity towards mosquito larvae, demonstrating a potential use of recombinant A. aquaticus for biological control of mosquitoes. PMID- 7993102 TI - Cell culture and PCR determination of poliovirus inactivation by disinfectants. AB - Inactivation of poliovirus type 1 by 1 N HCl, 1 N NaOH, 0.5 and 1.0 mg of free chlorine per liter, and UV light was compared by using cell culture and seminested PCR (30 cycles of reverse transcriptase-PCR plus 30 cycles of seminested PCR). A minimum contact time of 45 min with HCl, 3 min with NaOH, 3 and 6 min with 1.0 and 0.5 mg of free chlorine per liter, respectively, was required to render 1.64 x 10(2) PFU of poliovirus type 1 per ml undetectable by seminested PCR. In cell culture, a minimum contact time of 5 min to HCl, 30 s to NaOH, and 1 min to either chlorine concentration was required to render the viruses undetectable by the plaque assay method. No correlation was observed between results by PCR and cell culture when viruses were exposed to UV light. These data suggest that inactivated virus with intact nucleic acid sequences can be detected by PCR. PMID- 7993103 TI - Duplication of the lantibiotic structural gene in M-type 49 group A streptococcus strains producing streptococcin A-M49. AB - Streptococcin A-M49 is produced by certain strains of M-type 49 group A streptococci. The structural gene for streptococcin A-M49 was cloned after hybridization with a probe containing the scnA lantibiotic structural gene. Sequence analysis revealed a duplication of the scnA gene; each gene (scnA' and scnA") encoded a 51-amino-acid prepeptide. PMID- 7993104 TI - [Dose intensity in cancer chemotherapy (including high dose chemotherapy)]. AB - It has been difficult to compare the impact of different dosing practices in treatment programs. Hryniuk and colleagues retrospectively analyzed treatment outcome in a number of different tumors as a function of what they have termed dose intensity. They defined dose intensity as the amount of drug delivery per unit of time, expressed as mg/m2/wk, regardless of the schedule or route of administration. Relative dose intensity (RDI) is the amount of drug delivered per unit of time relative to an arbitrarily chosen standard single drug, or, for a combination regimen. Calculation of the dose intensity, therefore, require the assumption that differences in scheduling dose not influence treatment outcome. Retrospective reviews of the clinical literature indicate that dose intensity of single agent or combination chemotherapy correlates well with outcome in cancer of the breast, lung, ovary colon, or lymphoma. To confirm adequately the data obtained from retrospective review prospective randomized trials are required to determine whether dose (dose intensity) is independent determinant of outcome. In this paper prospective trials of dose intensity were reviewed and some of them in breast cancer, small cell lung cancer, ovarial cancer, malignant lymphoma, or germ cell tumor showed correlation between dose intensity and single anticancer agent regimens or combination regimens. High dose chemotherapy with supportive therapy such as administration of hematopoietic growth factor, autologous bone marrow transplantation, or peripheral blood stem cell transfusion, was also reviewed. Some of these modality showed the suggestive correlation between these therapeutic intensification and the prolongation of survival rate. Intensive chemotherapy for curable intent should be investigated very carefully in near future. PMID- 7993105 TI - [New strategy of breast cancer treatment]. AB - Incidence of the patients with breast cancer has been increased continuously in Japan and it will be the top of all kinds of cancers in female by the end of this century. Early detection of the disease is very important and thus the surgical treatment such as breast conserving therapy (BCT) is much more acceptable. However BCT should be performed carefully and individually for each case. The new hormonal treatments and the new anti-cancer agents are developed recently and powerful therapy with combination of these drugs and the others will be expected. PMID- 7993106 TI - [Early detection and diagnosis of breast cancer]. AB - Various kinds of modalities have been used to detect and diagnose breast cancer. In order to detect early breast cancer, mass screening has been widely performed with physical examinations in Japan and mammography in the U. S and European countries. After detecting some abnormalities within the breast under basic screening, further examinations are required for a precise diagnosis. For this purpose, ultrasonography and/or thermography are used as a noninvasive image examination, and aspiration biopsy cytology and/or surgical biopsy are employed for the final diagnosis. Mammography with highly qualified equipment and its adequate performance is thought to be the most useful modality in basic screening for detecting nonpalpable breast cancer. Ultrasonography is valuable for differentiating whether the lesions detected on screening are malignant or benign. Thermography seems better in analysing the malignant potential of the lesions detected by other examinations. Aspiration biopsy cytology (ABC) is employed for final diagnosis. Fine needle ABC has the highest sensitivity (90.8%) compared to other modalities in this department of Fukushima Medical College Hospital. Positive diagnosis on ABC is not needed for surgical biopsy. However, suspected or negative findings on ABC are required for two-step surgical biopsy which should be performed at the outpatient clinic to obtain detailed information about the biological characteristics as well as pathological diagnosis. PMID- 7993107 TI - [Controversies in the surgical options for the patient with primary breast cancer]. AB - We analysed the results of relapse free survivals for breast cancer patients treated with traditional mastectomy through 10 years of follow up. In the consecutive series of 162 patients with Stage III breast tumor, we noted that the mastectomy followed by radiation to axilla and adjacent area failed to confirm the efficacy to support the prevention for local and distant relapse in the past decade (1962-1974) (27.2%). The concepts of neoadjuvant and/or adjuvant chemotherapy were evolved primarily from clinical trials: these have been shown to influence favorably for the 228 patients with STAGE III in the next decade (1975-1985) (46.1%). Modified mastectomy, which involved removal of the breast, overlying skin and axillary contents but spares the pectoralis muscle, has recently been established as an entirely satisfactory approach for STAGE I (295 patients) and STAGE II (281 patients) breast carcinomas (1986-1991). Five-year relapse free survivals of these 2 categories calculated 93.7% and 86.8%, respectively. In recent studies, the many trials to breast conservation therapy reported, such as partial mastectomy plus nodes dissection with or without radiotherapy for selected patients with early cancer represent as effective results as modified mastectomy. Breast preservation has focused attention on the extent and distribution of cancer (multifocality, residual foci of surgical margin, etc) for clinicians. PMID- 7993109 TI - [Recent advances in radiotherapy for breast cancer]. AB - Radiotherapy for breast cancer has been performed as adjuvant lymph node irradiation after radical operation, irradiation for chest wall relapse, and palliative treatment for bone, lung and brain metastases. However, attention has been paid to irradiation of the breast as a conservative treatment. The role of radiotherapy in breast conservative treatment is to reduce local relapse after shrinkage of operation, and to enhance the cosmetic outcome. The indications of this treatment, technique of irradiation, effects and side effects of irradiation, and risk of radiation-induced cancer were discussed. In Japan, we have experience with this treatment. Breast conservation treatment and modified mastectomy showed the same results in local control and survival. Sometimes the cure and most cases of relief of complaints are attained for recurrent or advanced breast cancer by radiotherapy. High dose rate brachytherapy by 192-Ir showed high local control of uncontrollable tumor by external irradiation. And hyperthermia combined with radiotherapy is also effective for superficial (less than 3 cm in depth) tumor. Even in patients with lung and or brain metastases, radiotherapy sometimes showed complete remission for years. The standard method of radiotherapy for bone and brain metastases is 30 Gy/2 wks, and the symptom relief rate is over 80%. Oncologists should be made aware of the high complaint relief rate by radiotherapy. PMID- 7993108 TI - [Recent advance of hormonal treatment for breast cancer]. AB - Since ER positivity in breast cancer is highest in the early stage of its natural history, hormonal treatment should be given as the initial treatment after both surgery and recurrence. Tamoxifen and medroxyprogesterone acetate have been commonly used as the standard hormonal treatment with a response rate of 20-30% and a median duration of response of 6-10 months. New agents for hormone therapy include tamoxifen analogues, LH-RH analogues and aromatase inhibitors. They are now on or have just cleared phase studies. LH-RH analogue is a unique drug that is active for premenopausal patients and should be used as the first-line therapy for them. Aromatase inhibitors lower serum estrogen levels by inhibiting conversion from andreogens to estrogens, thus inducing regression of ER-positive tumors. They are used as the second-line treatment after tamoxifen failure for postmenopausal patients. An increasing body of information has been accumulated as to how the hormonal treatments affect breast cancer at subcellular levels. New approaches controlling growth factors such as anti-angiogenesis are under way. PMID- 7993110 TI - [Acquired resistance and cross-resistance of gemcitabine to cisplatin or vindesine in human lung cancer xenografted in nude mice]. AB - One of the problems in the treatment of cancer is the development of resistance to anti-tumor agents when used repeatedly. We described the induction of resistance, cross-resistance to cisplatin (CDDP) or vindesine (VDS) and the side effects of gemcitabine, a new Ara-C derivative, in human lung cancers, Mqnu-1 or H-74 xenografted in nude mice. We investigated the effects of 4-week observation period. Gemcitabine was effective and did not show the acquired resistance when given repeatedly. In contrast, CDDP but not VDS, when given repeatedly, showed a decrease of the anti-tumor effect in the second course. Gemcitabine was still effective to the large tumor grown after CDDP or VDS therapy. Thus, gemcitabine may not develop resistance nor show cross-resistance to CDDP or VDS. In addition, repeated treatment with gemcitabine was much safer than CDDP or VDS. These results suggest that gemcitabine is a candidate for the first choice drug in cancer treatment. PMID- 7993111 TI - [Study of in vitro cancer sensitivity of anticancer drugs by SDI (succinate dehydrogenase inhibition test)]. AB - To clarify the effect of fibroblast mixture in in vitro sensitivity test using SDI method. I have investigated the influence of fibroblast on the anticancer sensitivity test in a colon cancer cell line. The anticancer drugs, such as MMC (mitomycin C), CDDP (cisplatin) and 5-FU (5-fluorouracil) were contacted with colon cancer cells at 8 different concentrations on the intervals from 24 to 168 hours. The drug sensitivity of cancer cells in mixture of fibroblast was influenced by the kind of anticancer drugs, sensitivity of fibroblast itself, and the difference of sensitivity of cancer cell and fibroblasts. With the increase of percentage of fibroblast, the sensitivity of cancer cells became almost equivalent to that of fibroblast in 5-FU. But the sensitivity was not influenced by MMC or CDDP. And the difference of sensitivity was within about 27% by using 5 FU when the cancer cell ratio is 50%. Drug sensitivity of cancer cells was greatly influenced by drug concentration and contact time. Although the optimal contact time of sensitivity test depended on the kinds of drugs, 72 hours was considered to be optimal. PMID- 7993113 TI - [Diagnosis of hepatocellular carcinoma using chicken anti-monoclonal antibody--as tumor marker on the heterophilic hanganutziu-deicher antigen]. AB - The Hanganutziu-Deicher (HD) antigen is a heterophilic antigen with N glycolylneuraminic acid as the terminal carbohydrate, and has attracted much attention as one of tumor-associated antigens. This antigen is absent from normal tissues of human and chicken but expressed in human neoplasms. Extensive research on HD antigen has not be made yet to show the intimate correlation with human neoplasm, but it is attracting an attention as a diagnostic marker for the definition of cancer. We made two different chicken monoclonal antibodies against HD antigen as a pathological tool for hepatocellular carcinoma (HCC). The hybrid cell, which produced antibodies, were prepared by means of fusion technology with HD3 antigen-immunized chicken spleen cells and HAT-sensitive chicken B cell line termed R27H4. The two antibodies had a different characteristic, one recognized only glycolipid, and the other recognized glycoprotein as well as glycolipid. Glycolipid type HD antigen and glycoprotein type HD antigen were identified by using two chicken anti-HD monoclonal antibodies. Glycolipid type HD antigen was detected by flow cytometry in 4 out of 24 HCC samples (87.5%). In our study, increased serum levels of IgG type and/or IgM type HD antibodies were observed in 21 out of 24 patients with HCC (87.5%). The presence of these antibodies is attributable to the expression of the HD antigen in cells of HCC. Eleven out of 24 patients with HCC were negative for AFP and PIVKA-II, and 10 out of these 11 patients (90.9%) were positive for anti-HD antibodies. We consider that patients with HCC should be screened for HD antigen and antibody for an early diagnosis of hepatocellular carcinoma; the same as for AFP and PIVKA-II both of which are tumor-associated antigens that have been associated with for hepatocellular carcinoma. PMID- 7993112 TI - [Clinical significance of P-glycoprotein expression and multidrug resistance assessed by in vitro thymidine incorporation assay in patients with gastric carcinoma]. AB - Drug resistance in chemotherapy is a significant problem in the treatment of gastric carcinomas as well as other malignant tumors. Multidrug resistant cells frequently overexpress the 170 kDa P-glycoprotein (P-gp). Twenty-four fresh tumor specimens of gastric carcinoma were assessed by flow cytometric detection of P-gp using monoclonal antibody C219. Eight patients were P-gp positive. Differentiated gastric carcinomas contained significantly higher concentrations of P-gp positive. Incidence of P-gp positive case was high in advanced stage. Sixteen cases received in vitro chemosensitivity test assessed by thymidine incorporation assay (TIA). Seven of 9 multidrug resistant cases by TIA were P-gp positive, and all of 7 non-multidrug resistance were negative. Expression of P-gp and multidrug resistance were closely correlated (p < 0.01). Also, in 89 patients with operable gastric carcinoma, the relationship between multidrug resistance by TIA and their clinicopathologic features as well as their survival lengths were examined. Thirty-one of 89 specimens from gastric carcinoma patients were multidrug resistant by TIA. Patients with multidrug resistant group had a significantly poorer cumulative survival rate than non-multidrug resistant cases (p < 0.01). The multivariated analyses showed that multidrug resistance analyzed is useful indicator for prognosis (p < 0.1). We suggest that multidrug resistance cases or P-gp-positive cases of gastric carcinoma are highly malignant, and these determinations are clinically useful. PMID- 7993115 TI - [Phase I/II study of a combination regimen composed of cisplatin, carboplatin and etoposide against small cell lung cancer]. AB - Phase I/II study of combination regimen composed of cisplatin (CDDP), carboplatin (CBDCA) and etoposide (VP-16) [CPVP] was conducted for small cell lung cancer. The dose level of VP-16 was fixed at 100 mg/m2, while the dosages of CDDP and CBDCA administered at each of the 4 steps were 50/200, 60/200, 60/250 and 70/250 mg/m2, respectively. Nine patients were allocated to each step dose group. Toxicities were evaluated in the first 2 courses to determine the maximum tolerated dose (MTD). As a result, step 3 dosages proved to be MTD, and the dose limiting factor (DLF) was hematotoxicity, but gastro-intestinal toxicity was tolerated. The response (CR+PR) was found in 21 out of 23 patients with evaluable lesions (91%). In the 22 patients who had not received pretreatment, median survival time (M ST) was 16.4 months. These results suggest that the recommended dose is step 2, and that the CPVP regimen is both more tolerable and more effective than the standard regimen. The CPVP regimen warrants further study in phase III trials. PMID- 7993114 TI - [A basic and clinical study of CA 19-9-MP-Mitsui kit for determination of CA 19 9]. AB - Recently, the CA 19-9-MP-Mitsui kit (MP-kit) by a sandwich enzyme immunoassay using two mouse monoclonal antibodies of C192 and C241 for the determination of CA 19-9 was developed by Mitsui Pharmaceutical Co., Ltd.. We carried out basic and clinical studies of MP-kit for the serum CA 19-9 in comparison with the Immunoclone CA 19-9 EIA kit (I-kit) which was provided by Fuji-Rebio Company. It was found that MP-kit appeared to have excellent reproducibility with high sensitivity and specificity for CA 19-9. Furthermore, the coefficient of positive correlation was as high as 0.92 in serum CA 19-9 level between MP-kit and I-kit in the determination of serum CA 19-9 in 67 cases by each of two kits. On the other hand, with two kits, it was found that employment of a cut off value more than 70 U/ml brought a highest diagnostic efficiency for pancreatic and bile duct cancers, while employment of a cut off value of 37 U/ml which was used routinely resulted in a high false positive incidence, particularly in liver cirrhosis or hepatitis. From the results, it is concluded that a pertinent cut off value of CA 19-9 in serum was about 70 U/ml and MP-kit was available for determination of CA 19-9 in serum such as the other known kits on the market for CA 19-9. PMID- 7993116 TI - [Late phase II study with 21-consecutive-day oral administration of etoposide for malignant lymphoma]. AB - We conducted a multi-institutional (33 institutes), late phase II study with a 21 consecutive-day oral administration of etoposide for malignant lymphoma. Patient entry criteria were either those refractory to standard therapies or those for whom no appropriate therapy was available. A once-daily dose of 50 mg/body was administered for 21 consecutive days. Of the evaluable 83 among 88 entry patients, the overall response rate was 53.0% (44/83), including 10 CR; 52.5% (42/80, 9 CR) with non-Hodgkin's lymphoma and 100% (2/2, 1 CR) with Hodgkin's disease. Regarding abnormal laboratory findings, myelosuppression was observed; the incidence rates of leukopenia (23.3% with Grade 3), neutropenia (32.6%), hemoglobin decrease (17.4%) and thrombocytopenia (4.7%) were 70.9%, 65.1%, 54.7% and 19.8%, respectively. Major adverse reactions and their incidence were: anorexia 43.0%, alopecia 37.2%, nausea/vomiting 32.6%, fatigue 18.6%, stomatitis 15.1%, fever 7.0% and diarrhea 5.8%. Therefore, a 21-consecutive-day oral administration of 50 mg/body/day or 75 mg/body/day appears to be effective for the treatment of malignant lymphoma. PMID- 7993118 TI - [A case of lung metastasis from Meibomian gland carcinoma of eyelid with effective chemotherapy]. AB - A 47-year-old man was admitted to Shinshu University Hospital in 1992 because of cough and chest abnormal shadow. In 1987, he had an operation for Meibomian gland carcinoma of his right lower eyelid, and also received radiotherapy. His chest X ray film on admission showed tumor shadows in the bilateral upper lung fields. The chest CT scan showed tumors in the right S1 and the left S3. Bronchofiberscopic findings demonstrated stenosis of the right upper bronchus and an endobronchial mass occluding the left B3. A biopsy specimen of the endobronchial mass revealed sebaceous carcinoma, which was identical with that of the resected eyelid tumor. He received two courses of chemotherapy in a combination of CDDP 75 mg/m2 and ADM 50 mg/m2. The tumors on chest X-ray and CT scan became small by the chemotherapy. Bronchofiberscopy after the chemotherapy also revealed that the stenosis of the right upper bronchus improved and the endobronchial mass in the left B3 had disappeared. He died 8 months after initial chemotherapy with a response duration of 7 months. PMID- 7993117 TI - [Antiemetic efficacy of the repeated use of granisetron in multiple cycles of anti-cancer chemotherapy]. AB - Twenty-three patients with gynecological cancer who were treated with 85 cycles of cytotoxic chemotherapy containing platinum received intravenous granisetron repeatedly. Granisetron (3 mg/body) was drip-infused twice for each cycle at a 24 hour interval. The antiemetic efficacy was evaluated and compared for each day and each cycle, and analysed using the chi-square and H tests. There were no significant differences between the first cycle and the subsequent second through fifth cycles in the severity of nausea and the frequency of vomiting. The latter tended to increase in the second day of each cycle. These results indicated that granisetron does not decrease in antiemetic efficacy by repeated administration during multiple cycles of anti-cancer chemotherapy. PMID- 7993119 TI - [A case of poorly differentiated hepatic cell carcinoma which showed 90% decrease in size after chemotherapy with intraarterial infusion of mitomycin C and oral administration of tegafur]. AB - The patient was a 77-year-old man, admitted complaining of abdominal fullness and appetite loss. By ultrasonography and CT an 8 x 5 cm mass was discovered in S1 of the liver. Needle biopsy specimen from the lesion revealed poorly differentiated hepatic cell carcinoma. Because of his advanced age and the size of the tumor, surgical therapy was not used. Chemotherapy with intraarterial injection of mitomycin C 2 mg once a week and 800 mg of tegafur PO daily was given for 5 weeks until bone marrow suppression developed. After recovery of hematological data, tegafur 800 mg PO daily every other week was administered for a year. In the course of these therapies, the hepatic tumor became smaller, and the ultimate decrease rate was over 90% (PR). Thus far it seems that chemotherapy with tegafur might be tried in hepatic cell carcinoma cases in which surgery is not indicated. PMID- 7993120 TI - [Two cases of malignant effusion treated successfully by loco-regional administration of carboplatin]. AB - We encountered two cases of malignant effusion treated successfully by loco regional administration of carboplatin (CBDCA). One case was a 60-year-old male showing recurrent non-small cell lung cancer (adenocarcinoma) with pericarditis carcinomatosa. A drainage from the pericardial cavity was performed and a total dose of 600 mg (single dose, 300 mg) of CBDCA was administered into the cavity. Malignant effusion disappeared and radiographic improvement was also observed. No pericardial effusion was observed for about 4 months after the loco-regional treatment, till he died of lung cancer. Another case was a 58-year-old male having invasive thymoma (mixed cell type) with pleuritis carcinomatosa. He received palliative radiation therapy and systemic cancer chemotherapy concurrently. As a loco-regional therapy, drainage from the pleural cavity was performed, and 300 mg of CBDCA and 10 KE of OK-432 were administered into the cavity. A remarkable reduction of pleural effusion was observed after the therapy. No increase of pleural effusion has been observed radiographically for about 18 months, and the patient is still alive with the tumor. The side effects due to loco-regional administration of CBDCA were quite tolerable in both cases. PMID- 7993121 TI - [Improvement of clinical symptoms by UFT and TAM and a case of bone metastasis from breast carcinoma during pregnancy]. AB - At age 35, the patient was diagnosed with left breast carcinoma (T4bN0M0, Stage IIIb) during her first pregnancy, and underwent mastectomy of the left breast and bilateral oophorectomy. Although CPA was administered as adjuvant chemotherapy after the operation, left pelvic pain developed about a year after the operation, and bone metastasis was detected from the imaging diagnosis. Then, the therapy was switched to UFT (600 mg/day) and tamoxifen (20 mg/day), which markedly relieved the pain along with bone scintiscan (NC) and simple X-P (NC). Five years have passed since the operation, and the progress is excellent. There is neither increase of pain nor adverse reactions to drugs. Furthermore, the patient received breast reconstruction operation at her strong insistence in the third year after operation, and has achieved a high quality of life (QOL). PMID- 7993122 TI - [A case of inflammatory breast cancer treated with preoperative intra-arterial infusion chemotherapy]. AB - A 35-year-old female with inflammatory breast cancer was treated with preoperative intra-arterial infusion chemotherapy. One cycle consisted of cyclophosphamide 700 mg, epirubicin 20 mg and 5-FU 1,750 mg. After 4-cycles of intra-arterial infusion chemotherapy, the size of tumor and regional lymph nodes were remarkably decreased. Histological examinations revealed that almost all the cancer cells had disappeared in the resected specimen. In the patient, preoperative intra-arterial infusion chemotherapy was very effective in local control, which enabled us to perform a histologically curative operation. In conclusion, multimodal treatment including intra-arterial infusion chemotherapy is a promising treatment for inflammatory breast cancer. PMID- 7993123 TI - [A case of curatively operated gastric cancer with peritonitis carcinomatosa treated by intraperitoneal administration of CDDP.Etoposide and EAP therapy]. AB - Intraperitoneal administration of cisplatin (CDDP) etoposide (VP-16) and EAP therapy (combination chemotherapy with CDDP, adriamycin (ADM) and etoposide provided the curative resection for advanced gastric cancer with peritonitis carcinomatosa in a 48-year-old woman. She suffered from epigastralgia. CT shows the ascites, and ultrasonography shows Schnitzler metastasis. First, CDDP 100 mg and etoposide 200 mg were given intraperitoneally. Then, the ascites completely disappeared. Next, the patient underwent EAP therapy, after which Schnitzler metastasis disappeared, and total gastrectomy was performed. Macroscopically, it was of H0P0N0S2. Histopathologically, it was poorly differentiated adenocarcinoma and n0s2. She has been doing well with no evidence of recurrence for 18 months after operation. PMID- 7993124 TI - [A clinical study of sixteen polycythemia vera cases--acute myeloblastic leukemia in patients with polycythemia vera]. AB - The clinical course of 16 patients with polycythemia vera (PV), treated in the period 1982 to 1993, was shown. Splenomegaly occurred in three fourths of these patients (75%), and hypertension was a major symptom. Thrombosis such as myocardial infarction and cerebral infarction was noted. Eight patients was treated with myelosuppressive agents and the 8 other patients were treated with phlebotomy. A 70-year-old male who was treated with mitobronitol (DBM) developed acute myeloblastic leukemia (AML) 11 years later. He was treated with multi combination chemotherapy (BHAC-DMP), and entered complete remission, followed by early relapse. He became refractory to chemotherapy and died of acute pneumonia 6 months later. Median survival of 16 cases of PV was more than 10 years, and long term treatment and care are necessary. PMID- 7993125 TI - [Concomitant radiotherapy and chemotherapy with protracted low dose continuous infusion of 5-fluorouracil and cisplatin]. PMID- 7993126 TI - [Carboplatin treatment by continuous infusion in combination for relapsed and refractory acute myeloid leukemia]. PMID- 7993127 TI - [Clinical effects of granisetron and methylpredonisolone against delayed emesis and anorexia induced by anticancer agents]. PMID- 7993128 TI - [Interferon-alpha, beta, gamma]. AB - There are three types of interferons (IFN), alpha, beta and gamma. IFN-alpha is produced in the leukocytes infected with virus, while IFN-beta is from fibroblasts infected with virus. IFN-gamma is induced by the stimulation of sensitized lymphocytes with antigen or non-sensitized lymphocytes with mitogens. It is believed that IFN-alpha and beta originated from the same ancestral gene, whereas IFN-gamma did not. IFN has not only an antiviral activity, but also various kinds of biological activities including cell growth inhibition, immunosuppressive effects, enhancement of macrophage, natural killer (NK) cell, killer (K) cell and neutrophil functions, and cell differentiation-inducing activity. IFN also shows the antitumor activity resulting from the integration of the above-mentioned biological activities. IFN is also deeply involved in the pathogenesis of various diseases, e.g., collagen diseases such as SLE and rheumatoid arthritis, insulin-dependent diabetes mellitus, fulminant hepatitis, severe pancreatitis, nephritis, multiple sclerosis, allergic diseases, and atherosclerosis. At present, IFN is clinically used in therapy against virus infections such as hepatitis B and C, and for malignancies such as renal cell carcinoma, multiple myeloma, malignant melanoma, glioblastoma, skin cancers, malignant lymphoma and chronic myelogenous leukemia. PMID- 7993129 TI - Consumers and their families. PMID- 7993130 TI - Caring, curing, and brief therapy: a model for nurse-psychotherapy. AB - Traditional models of psychotherapy have failed to meet the demands for accessible, cost-effective, and accountable mental health services. This traditional approach to mental health based on the received view of science is deconstructed in terms of its cure-orientation and contrasted with the care orientation of nursing that is more consistent with postmodern ideas of science. Methods of brief, intermittent or possibility-oriented therapy are suggested as ways to actualize a care-orientation to mental health nursing that is more consistent with nursing's values and is more accessible to the needs of the consumer. PMID- 7993131 TI - Bridging the clinical-research gap through nursing collaboration. AB - The process of conducting research protocols on clinical psychiatric units presents many challenges for research and clinical staff alike, challenges that are especially daunting when the clinical psychiatric unit is not designed for or dedicated to research. This article describes an attempt to bridge the gap between clinical and research needs through nursing collaboration, focusing on the specific issue of managing treatment-resistant psychotic patients in a neuroleptic-free state before trial on clozapine. It suggests that applying research methods to the process of research itself is as necessary as applying them to the specific protocols conducted within it. PMID- 7993132 TI - Brief hospital treatment plans for persons with borderline personality disorder: perspectives of inpatient psychiatric nurses and community mental health center clinicians. AB - Despite growing recognition of the challenges inherent in helping persons with borderline personality disorder, systematic investigation of caring for this population in specific treatment situations is lacking. In this study, an innovative hospital treatment program for persons with borderline personality disorder was evaluated. Using an interpretive phenomenological approach, a team of researchers analyzed data from in-depth, individual interviews with inpatient psychiatric nurses and community mental health center clinicians (n = 13) and thereby identified a constitutive pattern, the paradoxes of helping. At a time when innovation in caring for persons with this disorder is sought, an examination of these paradoxes will help identify those practices to be abandoned, those to be extended, and those to be preserved. PMID- 7993133 TI - Effects of two caregiver-training programs on burden and attitude toward help. AB - The purpose of this research was to determine which caregiver-training program (CTP) was most beneficial to caregivers. Two types of CTPs, a behavior management program and a social skills program, were implemented. The effects of the CTPs on attitude toward asking for help, attitude about using adult day care, are caregiving burden were explored. Thirty-three caregivers volunteered to participate. Of the caregivers, the majority were female spouses (n = 22), 76% were over age 60, and 68% had some college education. Subjects were randomly assigned to one of two CTPs or a control group. Pretest was completed during the first phase of the training program. Both CTPs met for six sessions. The control group received no training. The posttest was conducted 1 month after completion of the CTPs. Differences between the three groups were analyzed by using ANOVA. No differences were observed between groups. Six of the subjects chose the alternate training program when given the opportunity for further training. Caregivers who participated in both CTPs experienced a decrease in objective burden and a more positive attitude toward asking for help and using adult day care. PMID- 7993134 TI - A profile of mood in ambulatory nursing home residents. AB - This study examined mood in 54 ambulatory nursing home residents. Female subjects reported significantly lower scores on the Anger-Hostility subscale than either men or normative subjects. Women also scored lower than normative subjects on the Vigor-Activity and Confusion-Bewilderment subscales, whereas men scored lower on the Fatigue-Inertia subscale. Both men and women reported below norm scores for the Tension-Anxiety subscale. Further study is needed to identify sociological factors that may explain diminished expression of mood in this vulnerable population, and to compare these findings with the mood profile of community dwelling elders. PMID- 7993135 TI - Hardiness and death attitudes: predictors of depression in the institutionalized elderly. AB - There are varied and high estimated prevalence rates of depression in the institutionalized elderly. Personality characteristics and attitudes are two attributes in the uniqueness of humans that have been overlooked in explaining depression. This study examined the relationships of hardiness and death attitudes to depression. The sample consisted of 90 consenting participants; 46 women and 44 men. The mean age of the sample was 73.3 years. This study produced the following three major findings: hardiness and depression are correlated; healthy death attitudes are related to low depression scores; and the combination of nonhardiness and health-limiting death attitudes are reliable predictors of depression in the institutionalized elderly. PMID- 7993136 TI - Psychiatric hospitalization as an experience of trauma. PMID- 7993137 TI - President's message: new mission statement and LRSP will guide ANNA's future. PMID- 7993138 TI - Personality, stress, coping, and sense of coherence among nephrology nurses in dialysis settings. AB - The goal of this study was to examine the relationships among personality types, personal and work-related stress, coping resources, and sense of coherence (SOC) among nephrology nurses in dialysis settings. Nurses (n = 49) from 13 dialysis units in New Mexico completed a demographic data form, Perceived and Nursing Stress Scales, SOC Scale, Coping Resources Inventory, and the Myers-Briggs Type Indicator (MBTI). The results indicated that there was a positive correlation between perceived personal stress and work-related stress, especially work load. Conversely, there were negative correlations between (a) both personal and work related stress with SOC, and (b) both coping resources and SOC with burnout. High levels of personal and work-related stress were related to inadequate coping resources. Regression analysis indicated that the main contributing factors to emotional exhaustion (a major component of burnout) were low SOC, lack of staff support, personal stress, and heavy work load. Increased utilization of coping resources may facilitate the nurses' management of personal and work-related stressors. PMID- 7993139 TI - CQI in action: benefiting our patients. AB - During 1993, the renal department of a suburban New Jersey hospital made the transition from quality assurance (QA) to continuous quality improvement (CQI). The chronic hemodialysis unit identified a problem based on the patient status at the beginning of the year, initiated steps to correct it, assessed the change by the end of the year, and developed plans to continue and improve the change. The effort to improve patient iron levels demonstrates one CQI activity undertaken. PMID- 7993140 TI - Family decision making about living related kidney donation. AB - Little information is available on how families make decisions about living related kidney donation. The purpose of this study, therefore, was to explore the family decision making process in identifying and selecting a living related kidney donor, to identify factors that assist or inhibit the decision making, and to explore issues and concerns raised by families about the experience. The qualitative method of grounded theory was used. Ten recipients, their living related donors, and their family members were interviewed individually and as a group prior to and after the transplant. Four decisions were required of most families. Three decision-making patterns--straightforward, moderately straightforward, and complex were identified as well as the factors that influenced the process. PMID- 7993142 TI - Nephrology nurse presents with acute cortical necrosis. PMID- 7993141 TI - Management of the peritoneal dialysis patient receiving radioactive iodine 131. AB - The patient met all expected outcomes while receiving I-131 and performing CAPD. As anticipated, the multidisciplinary approach proved to be effective in meeting this patient's needs. Careful planning and supportive care by the nephrology professionals resulted in a positive influence on F.A. and his family's acceptance of the prescribed treatment. Providing education for the nurses and patient decreased anxiety levels, and enabled F.A. and the nephrology nurses to cope with this difficult situation. The optimal delivery of nursing care was enhanced through patient and staff education, open communication and proper preparation of the patient, family, nurses, and environment for the safe administration of radioactive I-131. The nursing care of this patient was indeed an extraordinary experience. The purpose of this case study is to serve as a useful reference to other health care professionals who might face a similar dilemma. PMID- 7993143 TI - Case study of the anemic patient: epoetin alfa--focus on sexual function. AB - For patients with end-stage renal disease (ESRD) whose anemia is corrected with Epoetin alfa, a higher hematocrit typically results in increased well-being and renewed interest in life, including sexual activity. Paradoxically, this generally positive therapeutic outcome can result in sexual problems for the patient and his or her partner because of changing expectations. Understanding the physical and psychosocial causes of sexual dysfunction in patients with ESRD, as well as strategies for assessment and intervention, prepares nurses to anticipate sexual problems and intervene appropriately. PMID- 7993144 TI - Age factors in transplantation. PMID- 7993145 TI - Cisapride. AB - Renal patients often complain of vague abdominal symptoms compatible with a gastric motility disorder. Cisapride is a recently available prokinetic agent that improves motility and emptying of the upper gastrointestinal tract in patients on long-term dialysis. The drug is extensively metabolized in the liver producing metabolites with minimal pharmacologic activity. Adverse reactions are primarily gastrointestinal in nature and include abdominal cramps, flatulence, and diarrhea. PMID- 7993146 TI - Expanding the ANNA scope of practice. PMID- 7993147 TI - Influence of blood culture results on antibiotic choice in the treatment of bacteremia. AB - BACKGROUND: It is unclear how often blood culture results influence empiric antibiotic regimens. METHODS: To assess the frequency of antibiotic modification and the rates of proper documentation of blood culture results by house staff physicians, we prospectively evaluated 226 episodes of bacteremia in 199 patients. RESULTS: Antibiotics were changed in 49.6% of episodes of true bacteremias. Physicians were more likely to change therapy if gram-negative rods (odds ratio [OR], 3.19) or Staphylococcus aureus (OR, 3.12) were isolated, if the blood culture was obtained in the first 7 days of hospitalization (OR, 1.9), or if house staff physicians properly documented the culture results in the medical chart (OR, 3.8) (all P values, < .05). Documentation of positive blood culture results by house staff physicians was absent in 26% of patients, and it was observed less often in patients on the surgical service (OR, 0.35; P = .004) or if a contaminant was recovered (OR, 0.24; P < .001). Eighty-three percent of "true-positive" blood cultures, as compared with 55% of "contaminated" blood cultures, were documented with a note in the medical records (P < .0001). Rates of documentation were higher for gram-negative rods, for patients who were already receiving antibiotic therapy, and for those who had a change of therapy after the culture results became available (all P values, < .05). A multivariate logistic regression model showed that documentation of the blood culture result (OR, 1.78; P = .006) or a positive culture within 7 days of hospitalization (OR, 1.49; P = .01) was independently associated with a change in therapy. CONCLUSIONS: In a significant proportion of patients with bacteremia, the blood culture result may not be the most important factor that determines antibiotic choice. Bacteremia is not adequately documented by house staff physicians in up to a quarter of patients. PMID- 7993148 TI - Adherence to aspirin in the prevention of myocardial infarction. The Physicians' Health Study. AB - BACKGROUND: The primary aim of this article was to explore, in subgroup analyses, whether participants with differing frequencies of aspirin consumption in a randomized, double-blind, placebo-controlled, primary prevention trial had different magnitudes of benefit in the prevention of myocardial infarction. Secondary aims were to identify factors associated with adherence and to examine the relationship of adherence with cardiovascular outcomes in the placebo group. METHODS: The Physicians' Health Study randomized 22071 US male physicians who were free of myocardial infarction and cerebrovascular disease at baseline. The average follow-up during the aspirin component of the trial was 60.2 months. Baseline cardiovascular risk factors and adherence to therapy during the trial were assessed by questionnaire; cardiovascular outcomes were reported by questionnaire and confirmed by record review by an Endpoints Committee. RESULTS: Several cardiovascular disease risk factors assessed at baseline were related to poor adherence (taking < 50% of study tablets): cigarette smoking, obesity, lack of exercise, and history of angina. After adjusting for baseline differences in risk factors, participants in the aspirin group with excellent adherence (taking at least 95% of study tablets) had a statistically significant 51% reduction in myocardial infarction compared with those with excellent adherence in the placebo group. Those in the aspirin group with poor adherence had a smaller, non significant reduction in risk of myocardial infarction (a 17% reduction associated with taking < 50% of study tablets). In the placebo group better adherence was not associated with decreased risk of myocardial infarction, but was strongly associated with decreased risk of death. CONCLUSIONS: These subgroup data raise the possibility that a less than alternate day aspirin regimen may yield lower benefits in the prevention of myocardial infarction. Alternate explanations are that these analyses reflect either the play of chance or effects of uncontrolled confounding since comparisons were no longer randomized. Randomized trials are necessary to address the question of frequency of administration of aspirin to achieve optimal benefits in primary prevention of myocardial infarction. PMID- 7993149 TI - A rapid test for infectious and inflammatory enteritis. AB - BACKGROUND: Inflammatory illnesses are an indication for specific diagnostic studies and possible antimicrobial therapy. The presence of fecal leukocytes has been used as a marker of inflammatory diarrhea; however, microscopic examination of the fecal smear is unreliable if the specimen is transported, refrigerated, frozen, or collected by swab. OBJECTIVE: To evaluate a rapid, sensitive, semiquantitative test for detection of fecal leukocytes using antilactoferrin latex bead agglutination (LFLA), a test that remains sensitive even after specimens are refrigerated, frozen, or stored on swabs. METHODS: LFLA titers were determined in stool specimens from previously healthy volunteers before and after experimental infection with different enteric pathogens and from patients with nosocomial diarrhea caused by Clostridium difficile. RESULTS: Healthy controls and subjects with noninflammatory diarrhea caused by Vibrio cholerae consistently demonstrated LFLA titers less than 1:50. In contrast, subjects with inflammatory diarrhea caused by Shigella species and C difficile had markedly elevated titers. Titers for subjects with experimental shigellosis ranged from 1:50 to 1:3200, with seven (78%) of nine at 1:400 or greater. Titers for patients with C difficile enteritis ranged as high as 1:1200, with six (50%) of 12 at 1:400 or greater. Subjects with experimental enteropathogenic Escherichia coli infection also had elevated titers, ranging from 1:100 to 1:1600, with three (43%) of seven at 1:400 or greater. Titers for subjects with experimental enterotoxigenic E coli infection were moderately elevated, with nine (53%) of 17 ranging from 1:50 to 1:200 (only one [6%] of 17 was > or = 1:400), suggesting a mild inflammatory process. CONCLUSIONS: The fecal LFLA assay distinguishes inflammatory from noninflammatory diarrhea, may provide new information on mildly inflammatory processes, and may be a useful, rapid test in a diagnostic algorithm for acute, infectious diarrheal illnesses. PMID- 7993150 TI - Efficacy of pneumococcal vaccination in adults. A meta-analysis of randomized controlled trials. AB - BACKGROUND: Because of the prevalence of pneumococcal pneumonia, the substantial morbidity and mortality associated with many pneumococcal infections, and an increase in the incidence of antibiotic resistance among pneumococcal isolates, considerable efforts for disease prevention have been made using a polyvalent polysaccharide pneumococcal vaccine. Despite numerous clinical trials of the vaccine, its efficacy in the prevention of pneumococcal infections and other clinically relevant medical outcomes in adults remains uncertain. METHODS: To assess quantitatively the efficacy of pneumococcal vaccination, a MEDLINE literature search, manual reviews of article bibliographies, and communications with pneumococcal vaccine investigators were used to identify randomized controlled trials of the pneumococcal vaccine. Independent review of 594 articles revealed nine randomized trials with 12 vaccine and control study groups that evaluated clinically relevant outcomes in adults. To estimate a summary effect size for all outcomes, Mantel-Haenszel odds ratios (ORs) and Dersimonian and Laird rate differences (RDs) and their associated 95% confidence intervals (CIs) were computed. RESULTS: Summary ORs demonstrated a statistically significant protective effect of the vaccine for four pneumococcal infection-related outcomes: definitive pneumococcal pneumonia (OR = 0.34; 95% CI = 0.24 to 0.48), definitive pneumococcal pneumonia for vaccine-containing pneumococcal antigen types only (vaccine types only) (OR = 0.17; 95% CI = 0.09 to 0.33), presumptive pneumococcal pneumonia (OR = 0.47; 95% CI = 0.35 to 0.63), and presumptive pneumococcal pneumonia (vaccine types only) (OR = 0.39; 95% CI = 0.26 to 0.59). The summary RDs, which account for heterogeneity among studies, confirmed a statistically significant protective effect for two of these same outcomes: definitive pneumococcal pneumonia (RD = 4/1000; 95% CI = 0/1000 to 7/1000) and definitive pneumococcal pneumonia (vaccine types only) (RD = 8/1000; 95% CI = 1/1000 to 16/1000). Summary ORs and RDs failed to demonstrate a protective effect for pneumonia (all causes), bronchitis, and mortality (all causes) or mortality due to pneumonia or pneumococcal infection. Subgroup analyses showed that for all four pneumococcal infection-related outcomes, vaccine efficacy differed for high- and low-risk subjects, demonstrating efficacy for low-risk subjects and lack of efficacy for high-risk subjects. CONCLUSIONS: Pneumococcal vaccination appears efficacious in reducing bacteremic pneumococcal pneumonia in low-risk adults. However, evidence from randomized controlled trials fails to demonstrate vaccine efficacy for pneumococcal infection-related or other medical outcomes in the heterogeneous group of subjects currently labeled as high risk. PMID- 7993151 TI - Dobutamine-atropine stress echocardiography in elderly patients unable to perform an exercise test. Hemodynamic characteristics, safety, and prognostic value. AB - OBJECTIVE: To establish the hemodynamic effects, safety, and prognostic value of dobutamine-atropine stress echocardiography in patients 70 years of age or older. DESIGN AND SETTING: Observational study at a university hospital. PATIENTS: One hundred seventy-nine patients (mean age, 75 years; range, 70 to 90 years) referred for chest pain (n = 73) or preoperative risk assessment for major vascular noncardiac surgery (n = 106). MEASUREMENTS: All patients underwent clinical evaluation and dobutamine-atropine stress test. RESULTS: One hundred seventy-nine stress tests were performed. Test end points were the target heart rate (85% of theoretical maximum heart rate), reached in 165 tests (92%); inadequate echo images, two tests (1%); and side effects, 12 tests (7%). Side effects that caused a premature end of the test were severe chest pain (n = 5 [2.8%]), electrocardiographic changes (n = 1 [0.6%]), hypotension (n = 2 [1.1%]), chills (n = 2 [1.1%]), and cardiac arrhythmias (paroxysmal atrial fibrillation) (n = 2 [1.1%]). New wall motion abnormalities as a marker of myocardial ischemia occurred in 50 tests (28%). No death or myocardial infarction occurred during the test. Perioperative events occurred in 12 patients (four cardiac deaths, three myocardial infarctions, and five episodes of unstable angina). During 16 +/- 6 months (mean +/- SD) of follow-up of 166 patients, 22 cardiac events occurred (eight cardiac deaths, four myocardial infarctions, and 10 episodes of unstable angina pectoris). By multivariate regression analysis, only perioperative cardiac events (odds ratio, 51; 95% confidence interval, 5.8 to 454) and late cardiac events (odds ratio, 5.2; 95% confidence interval, 2.0 to 14) were correlated with new wall motion abnormalities during stress. CONCLUSION: Dobutamine-atropine stress echocardiography is a feasible and safe test for assessing elderly patients with suspected and/or proven coronary artery disease, providing useful prognostic information for perioperative and late cardiac risk with relatively few side effects. PMID- 7993152 TI - Gonococcal arthritis in an era of increasing penicillin resistance. Presentations and outcomes in 41 recent cases (1985-1991). AB - BACKGROUND: To assess the impact of recent reports of disseminated gonococcal infection caused by penicillin-resistant organisms, we reviewed the presenting features, clinical course, and outcomes of a group of patients with gonococcal arthritis treated in recent years. METHODS: We reviewed the records of all cases of acute arthritis associated with a culture positive for Neisseria gonorrhoeae at our institution from July 1985 through December 1991. RESULTS: Forty-one cases were identified. Patients included 34 women and 38 blacks; the mean age was 22.6 years. Duration of symptoms averaged 4.8 days at presentation. Other features included migratory arthralgias (n = 27), urogenital symptoms or signs (n = 26), fever (n = 21), and skin lesions (n = 16). Comorbid conditions included intravenous drug use (n = 8) and systemic lupus erythematosus (n = 3). The knee was the most commonly affected joint. Positive culture results were obtained from 32 urogenital samples (86%), 14 synovial fluid samples (44%), seven rectal samples (39%), four blood samples (12%), and two throat samples (7%). All synovial fluid samples with positive culture results had white blood cell counts higher than 20.0 x 10(9)/L. Response to therapy with penicillin and/or ceftriaxone was prompt, and mean duration of hospitalization was 5.8 days. Patients who required longer hospitalization had a higher mean erythrocyte sedimentation rate and higher frequencies of positive synovial fluid culture results and comorbid conditions. Penicillin sensitivity could be determined in 30 patients on the basis of clinical response or in vitro testing. Among these patients, two cases of penicillin-resistant organisms were identified, one beta lactamase positive and one beta-lactamase negative. CONCLUSIONS: The clinical features of patients with gonococcal arthritis have changed very little since the last large reported series over a decade ago. Underlying conditions appear to be more common, but response to antibiotic therapy and eventual outcome remain excellent. The finding of penicillin-resistant organisms in at least 5% of patients reinforces recent recommendations that third-generation cephalosporin agents be used as initial therapy for disseminated gonococcal infections until drug susceptibilities are known. PMID- 7993153 TI - Intranasal fluticasone propionate is more effective than terfenadine tablets for seasonal allergic rhinitis. AB - BACKGROUND: We compared the efficacy and tolerability of the intranasal corticosteroid fluticasone propionate with that of the antihistamine terfenadine in patients with seasonal allergic rhinitis. METHODS: Two hundred thirty-two adults and adolescents with seasonal allergic rhinitis received intranasal fluticasone propionate (200 micrograms once daily), terfenadine tablets (60 mg twice daily), or placebo for 2 weeks in a double-blind, randomized, parallel group study. Main outcome measures were clinician- and patient-rated individual and total nasal symptom scores (based on ratings of nasal obstruction, sneezing, nasal itching, and rhinorrhea); clinician-rated overall response to therapy; changes in nasal inflammatory cell counts; adverse events; and morning plasma cortisol concentrations. RESULTS: Both clinician- and patient-rated total and individual nasal symptom scores were significantly lower in the fluticasone group than in either the terfenadine group or the placebo group at nearly every measured time point throughout the treatment period. After 2 weeks of therapy, clinician-rated total nasal symptom scores decreased by 49% in the fluticasone group compared with 27% in the terfenadine group and 19% in the placebo group. In general, therapy with terfenadine was not statistically distinguishable from that with placebo based on patient-rated total or individual nasal symptom scores. According to clinician ratings, 64% of fluticasone-treated patients compared with 49% and 44% of patients treated with terfenadine and placebo, respectively, experienced significant or moderate improvement. A greater percentage of fluticasone-treated patients compared with either terfenadine- or placebo-treated patients experienced reductions in intranasal eosinophil and basophil counts after 2 weeks of therapy. No unusual or serious drug-related adverse events were reported. Morning plasma cortisol concentrations after 2 weeks of therapy did not differ among groups. CONCLUSION: Fluticasone aqueous nasal spray, a well tolerated corticosteroid preparation that can be administered once daily, is more effective than terfenadine tablets or placebo in controlling symptoms of seasonal allergic rhinitis. PMID- 7993154 TI - Esophageal candidiasis in patients infected with the human immunodeficiency virus. A decision analysis to assess cost-effectiveness of alternative management strategies. AB - BACKGROUND: Currently no consensus exists concerning the timing of upper endoscopy and the choice of antifungal therapy for patients infected with the human immunodeficiency virus who also have esophageal candidiasis. The objective of this research was to determine the clinical and economic effects of alternative management strategies for these patients. METHODS: Decision analysis was used to evaluate the outcomes, costs, and cost-effectiveness of two strategies for the diagnostic workup and treatment of patients infected with the human immunodeficiency virus with dysphagia and/or odynophagia: (1) empiric--a strategy to treat all patients empirically with an oral antifungal agent for up to 4 weeks; and (2) initial esophagogastroduodenoscopy (EGD)--a strategy to perform EGD on all patients and to treat only those with esophageal candidiasis with an oral antifungal agent for up to 4 weeks. Within each strategy, three antifungal regimens were evaluated: ketoconazole, 200 mg daily; fluconazole, 100 mg daily; and ketoconazole, 200 mg daily, for 2 weeks followed by fluconazole, 200 mg daily, for 2 weeks in nonresponders. Information on the probability of esophageal candidiasis in patients with esophageal symptoms and the efficacy of antifungal therapy was obtained from the literature. The costs for diagnostic workup were estimated using both teaching hospital charges and Medicare reimbursement payments. The costs of antifungal therapy were estimated from local pharmacy charges. The average cost per complete response and incremental cost effectiveness were calculated and subjected to sensitivity analysis. RESULTS: Using the best available evidence for antifungal efficacy, empiric fluconazole was the most cost-effective strategy for all probabilities of esophageal candidiasis that were more than 0.55. Using teaching hospital charges in our base case analysis, the average costs per complete response for empiric fluconazole and initial EGD and fluconazole were $2706 and $3141, respectively. The incremental cost-effectiveness of initial EGD and fluconazole compared with empiric fluconazole was $3792 per additional complete response. When the cost effectiveness of the two strategies was compared as the cost of diagnostic workup was varied, initial EGD and fluconazole became the dominant strategy when the diagnostic workup cost fell below $710, a figure that is less than the current Medicare reimbursement payment. CONCLUSIONS: From the perspective of the payer of medical care, empiric fluconazole is the most cost-effective strategy for the initial management of patients infected with the human immunodeficiency virus with esophageal symptoms. PMID- 7993155 TI - The triglyceride issue revisited. Findings from the Helsinki Heart Study. AB - BACKGROUND: In clinical practice, high triglyceride level is recognized as an indicator of increased risk of coronary heart disease (CHD), while most epidemiological studies have shown that triglyceride level is not an independent risk factor for CHD. In an effort to explain this discrepancy we reanalyzed the Helsinki Heart Study data in the light of findings from recent clinical studies related to the insulin resistance syndrome. METHODS: The log-linear modeling technique was used to study the pattern of cross-sectional interdependence of triglyceride level, high-density lipoprotein cholesterol (HDL-C) level, low density lipoprotein cholesterol level, blood pressure, and blood glucose level. The CHD risk associated with different combinations of levels of triglycerides, HDL-C, and blood pressure was assessed via Cox proportional hazards models. RESULTS: Triglycerides occupied a central role in the pattern of associations of the factors studied; in particular, the associations with HDL-C level, blood pressure, and blood glucose level were without threshold values. The prevalence of high triglyceride level plus low HDL-C level was strongly associated with blood pressure and blood glucose level, while the prevalence of low HDL-C level alone was not. Only the subgroup with both high triglyceride and low HDL-C levels showed a substantial CHD risk, while those with low HDL-C levels alone or high triglyceride levels alone showed a marginal risk. CONCLUSIONS: Our results suggest that triglycerides play a central mediating role in the occurrence of several CHD risk factors, especially those related to the insulin resistance syndrome. Because of these interdependencies, the question of an independent effect of triglycerides is not relevant, and when assessing CHD risk, triglycerides should be considered jointly with HDL-C. PMID- 7993156 TI - Enhanced susceptibility to amiodarone-induced hypothyroidism in patients with thyroid autoimmune disease. AB - BACKGROUND: The iodine-rich antiarrhythmic drug, amiodarone, can induce both thyrotoxicosis and hypothyroidism, the former being more frequent in iodine deficient areas, the latter in iodine-sufficient areas. In this study we evaluated prospectively thyroid function in amiodarone-treated patients with positive or negative baseline thyroid autoantibody test results who resided in a moderately iodine-deficient area of Italy. SUBJECTS: Two groups of patients received long-term amiodarone treatment: Group 1 included 13 patients with negative thyroid autoantibody test results. Group 2 consisted of seven patients with positive thyroid autoantibody test results and thyroid ultrasound patterns compatible with Hashimoto's thyroiditis. The control group (group 3) included 16 untreated euthyroid patients with Hashimoto's thyroiditis. All subjects resided in a mildly iodine-deficient area of Italy (Southern Sardinia) and had low urinary iodine values. Patients in groups 1 and 2 had markedly elevated urinary iodine excretion during treatment. The follow-up period ranged from 6 to 29 months in group 1, from 4 to 9 months in group 2, and from 12 to 55 months in group 3. RESULTS: Two (15%) of 13 patients in group 1 with nodular goiter developed thyrotoxicosis. No patient in this group developed circulating thyroid autoantibodies. Five (71%) of seven patients in group 2 became hypothyroid after 4 to 9 months of amiodarone treatment associated with a rise in serum thyroid autoantibody levels. No patient in group 3 became hypothyroid. CONCLUSIONS: (1) Amiodarone administration can cause both thyrotoxicosis and hypothyroidism. (2) Hypothyroidism is far more frequent in patients with preexisting thyroid autoimmune disease. (3) Amiodarone can modify the natural history of Hashimoto's thyroiditis. (4) Circulating thyroid autoantibodies do not appear in amiodarone treated patients who have negative test results prior to therapy. PMID- 7993157 TI - Interobserver variability in the interpretation of chest roentgenograms of patients with possible pneumonia. AB - BACKGROUND: Previous studies have found considerable interobserver variability in the roentgenographic diagnosis of pneumonia. In this study we determined the impact of experience on interobserver variability in the interpretation of chest roentgenograms of patients with pneumonia and defined the characteristics of chest roentgenograms interpreted as pneumonia by all groups. METHODS: The chest roentgenograms of 15 consecutive patients with a clinical and roentgenographic diagnosis of pneumonia were read by a convenience sample of 10 first-year and 20 fourth-year medical students, 21 medical residents, and 21 staff physicians from the department of medicine. Three board-certified radiologists served as the gold standard. The majority rule decision and logistic regression analysis were used to analyze agreement among the various groups of observers. RESULTS: Agreement with the majority decisions of the gold-standard radiologists on the presence or absence of pneumonia for all observations of the various groups were as follows: original radiologist, 87%; first-year medical students, 59%; fourth-year medical students, 54%; medical residents, 66%; and attending staff, 72%. Chest roentgenograms with dense lobar or segmental opacities were generally interpreted as pneumonia by all observers. Patchy opacities caused major disagreements and were usually read as not being due to pneumonia. Bronchopneumonia was not diagnosed by any of the observers. Air bronchograms, atelectasis, and chronic obstructive lung disease were usually not recognized by the nonradiologists. CONCLUSIONS: There is considerable interobserver variability in the roentgenographic diagnosis of pneumonia. This variability does not improve with increasing experience. Dense lobar or segmental opacities are uniformly recognized as pneumonia while patchy opacities result in a variety of interpretations. PMID- 7993158 TI - HLA-DR5 antigen. A genetic factor influencing the outcome of hepatitis C virus infection? AB - BACKGROUND: Prognosis may be quite different among individuals infected with hepatitis C virus (HCV): a chronic liver disease is believed to occur in half the patients while in the other half there are no signs of histologic progression of liver damage. The host immune response might play an important role in such different outcomes. A relationship has been shown between HLA genes and immune response to viral hepatitis B, but to our knowledge, no evidence of an association with HCV has been reported so far. We investigated whether HLA class II alleles might influence the outcome of HCV infection. METHODS: Eighty-seven individuals, positive for anti-HCV by second-generation enzyme-linked immunosorbent assay and recombinant immunoblot assay tests, enrolled from May 1, 1991, to June 31, 1992, were evaluated. Thirty-six were symptom-free subjects found to have HCV antibodies when screened for blood donation: they all had normal results of liver function tests, normal results of physical examination, and normal hepatobiliary ultrasonography. Fifty-one were patients diagnosed as having a chronic liver disease by percutaneous liver biopsy specimen; histologic assessment was chronic persistent hepatitis in 15, chronic active hepatitis in 28, and liver cirrhosis in eight. A group of 231 donors of platelets and bone marrow, negative for anti-HCV, was used as a control population. All participants were typed for HLA class II antigens (DR and DQ) using National Institutes of Health recommended microlymphocytotoxicity test and were followed up by means of alanine aminotransferase and HCV testing for at least 1 year. RESULTS: Frequency of HLA-DR5 antigen was higher in symptom-free anti-HCV-positive individuals (52.8%) than among HCV-related patients with chronic liver disease (13.7%). The difference was statistically significant (corrected P value = .005; 95% confidence interval, 19.6% to 58.6%); between DR5 and long-term evolution of hepatitis C, there was a negative association (relative risk = 0.142). Moreover, frequency of HLA-DR5-positive subjects appeared to be inversely proportional to severity of liver disease (52.8% in symptom-free patients, 26.6% in patients with chronic persistent hepatitis, 10.7% in patients with chronic active hepatitis, and 0% in patients with liver cirrhosis, P < .001). CONCLUSIONS: Our results point to a strict relationship between HLA haplotype and ability of immune response to influence the outcome of HCV infection. Presence of HLA-DR5 antigen appears as a protective factor against a severe outcome of chronic infection, being correlated with a benign evolution of the infection, often asymptomatic, or a less severe chronic liver disease. PMID- 7993159 TI - A detailed evaluation of patients with acute pulmonary embolism and low- or very low-probability lung scan interpretations. AB - BACKGROUND: To determine the clinical characteristics of patients with pulmonary embolism (PE) and low- or very-low-probability ventilation-perfusion lung scan interpretations. METHODS: A retrospective analysis of the data obtained during the Prospective Investigation of Pulmonary Embolism Diagnosis study was performed. The clinical characteristics of patients with acute PE and low- or very-low-probability lung scan interpretation (false-negative interpretations) were compared with patients who had low- or very-low-probability lung scan interpretations and no evidence of acute PE (true-negative interpretations). RESULTS: Of the 1493 patients who gave consent to participate in the Prospective Investigation of Pulmonary Embolism Diagnosis study, 399 patients had angiographic or autopsy evidence of acute PE. Pulmonary embolism was excluded in 960 patients. Patients with false-negative lung scan interpretations more commonly had a history of immobilization (P < .0001), trauma to the lower extremities (P < .003), recent surgery (P < .002), or central venous instrumentation (P < .04) compared with patients with true-negative lung scan interpretations. In patients with low- or very-low-probability lung scan interpretations and none of the above-mentioned risk factors, the prevalence of PE was only 4.5%. In contrast, for patients with low- or very-low-probability lung scan interpretations and two or more of the above-mentioned risk factors, the prevalence of PE was 21%. CONCLUSIONS: Patients with a history of immobilization, trauma to the lower extremities, recent surgery, or central venous instrumentation were more likely to have false-negative lung scan interpretations. Therefore, this population warrants special attention when deciding on the need for peripheral venous studies or angiography in patients with low- or very-low-probability lung scan interpretation. PMID- 7993160 TI - Tolerability, safety, and acceptability of zidovudine prophylaxis in health care workers. AB - OBJECTIVE: To evaluate the safety, tolerability, and acceptability of zidovudine used for prevention of human immunodeficiency virus (HIV) transmission to health care workers. METHODS: Prospective study between January 1989 and December 1992 at a suburban New York City medical center of health care workers who had percutaneous or permucosal exposures to blood or body fluids of HIV-infected patients. The zidovudine regimen offered was 200 mg orally every 4 hours for 42 days. RESULTS: Only 60 (53%) of 113 health care workers chose to take zidovudine, and only 21 (35%) of these health care workers completed the recommended 42-day course of therapy. Men were more likely than women to choose zidovudine therapy (P = .06), and a greater proportion of men completed the full 42 days of zidovudine therapy (P = .09). The most frequent reason for stopping treatment prematurely was clinical adverse reactions (n = 18 [30%]). Overall, clinical adverse events occurred in 44 (73%) of those taking zidovudine, with the most frequent events being nausea (n = 28 [47%]), headache (n = 21 [35%]), and fatigue (n = 18 [30%]). Selected laboratory parameters (hemoglobin level, hematocrit, alanine aminotransferase level, and white blood cell, granulocyte, and platelet counts) were compared at baseline and at week 4. Of interest, platelet counts were significantly more likely to increase by week 4 than to remain the same or decrease (P = .035). This observation may shed light on the mechanism of platelet elevation seen in zidovudine-treated patients infected with HIV. None of the laboratory changes was considered clinically significant. Of the 42 health care workers followed up for 3 months or longer (range, 3 to 32 months), none had undergone HIV antibody seroconversion. CONCLUSIONS: Zidovudine therapy is poorly accepted and tolerated by health care workers, at least in the dosage regimen used in this study. Alternative prophylactic regimens are needed. PMID- 7993161 TI - Can physicians warn patients of potential side effects without fear of causing those side effects? AB - BACKGROUND: When initiating treatment, it has been shown that only one quarter of the physicians discuss potential side effects with patients. There are several possible reasons, but, in particular, many physicians are concerned that the power of suggestion may lead some patients to experience an increase in side effects if they are fully informed. Accordingly, this study was designed to determine whether providing patients with information about potential side effects of new medications increases the reported incidence of those side effects. METHODS: All clinic patients are randomly assigned to one of four firms. Two firms served as the intervention group and two served as control groups. All patients receiving new prescriptions for the angiotensin-converting enzyme inhibitors, trimethoprim/sulfamethoxazole, or nonsteroidal anti-inflammatory drugs were recruited. Patients without telephones were excluded. Intervention patients received verbal instructions and a handout describing the name, purpose, dose, and three most common side effects of the drug. Control patients received usual discharge instructions. Patients were interviewed 14 to 21 days later using a standardized questionnaire. RESULTS: There was no difference in incidence of targeted side effects for specific medications between the study groups (38% vs 37%). Study groups were similar with regard to age, sex, financial status, and type of medication prescribed. CONCLUSION: Informing patients of potential side effects prior to starting a new medication does not lead to an increased incidence of those side effects. This should not be a reason for physicians to avoid warning patients of potential side effects. PMID- 7993162 TI - The appropriateness of use of cardiovascular procedures in women and men. AB - OBJECTIVE: To determine whether there are differences between women and men in the appropriateness of use of cardiovascular procedures. DESIGN: Retrospective chart review. SETTING: Thirty hospitals located in New York State. PATIENTS: Random sample of 3979 patients undergoing coronary angiography, percutaneous transluminal coronary angioplasty, or coronary artery bypass graft surgery in 1990. MEASURES: We evaluated two measures: (1) the percent of women and men who underwent cardiovascular procedures for appropriate, uncertain, and inappropriate indications and (2) for coronary angiography patients, the prognostic exercise stress treadmill score that predicts before the coronary angiogram the 5-year probability of death from a cardiovascular event. RESULTS: The inappropriate rate of use of cardiovascular procedures was low and not significantly different for men and women (4% vs 5% for coronary angiography; 4% vs 3% for percutaneous transluminal coronary angioplasty; and 2% vs 3% for coronary artery bypass graft surgery, respectively), and the use of these procedures for uncertain reasons also did not vary significantly by gender. There was also no significant gender difference in the predicted risk of death from a cardiovascular event for coronary angiography patients: 24% of men and 22% of women were at high risk (ie, < 75% 5-year survival rate) and 20% and 16%, respectively, were at low risk (ie, > or = 95% 5-year survival rate). CONCLUSION: Based on two indicators, the RAND appropriateness score and the Duke prognostic exercise treadmill score, we were unable to find any evidence of a difference in the clinical appropriateness of use of these three cardiovascular procedures between women and men. PMID- 7993163 TI - Evaluation of back pain secondary to spinal epidural hematoma associated with aspirin intake and a partial platelet glycoprotein Ia/IIa deficiency. AB - We report a case of spontaneous spinal epidural hemorrhage with three unusual features: (1) the hemorrhage was associated with aspirin ingestion and a reduced level of platelet glycoprotein Ia/IIa; (2) the patient presented with typical severe back pain but without neurologic dysfunction; and (3) the patient initially recovered without surgical decompression but suffered from recurrent epidural hematoma. PMID- 7993164 TI - Four methods for characterizing disability in the formation of function related groups. AB - The Functional Independence Measure-Function Related Groups (FIM-FRGs) were developed to classify medical rehabilitation inpatients into homogeneous groups based on length of stay (LOS). Patients are first grouped into clinically relevant rehabilitation impairment categories, then by functional status, as expressed by the FIM, and in certain cases by patient age. The statistical approach used to form the final groupings was a recursive partitioning algorithm applied to the FIM scores and patient age within impairment category. This analysis compares four FIM-FRG classification schemes developed from four scale sets that combine FIM items differently: (1) use of the 18 FIM items as separate variables, (2) the combination of FIM items into six clinical subscales, (3) the combination of the six clinical subscales into motor and cognitive subscales, and (4) the combination of all FIM items into a single scale. The FIM-FRG schemes explain similar amounts of variance in the logarithm of LOS and contain approximately equal numbers of FRGs. The motor and cognitive subscale scheme is recommended for use in payment, however, this scheme and the other schemes have additional uses. Each FRG scheme provides different insight into the clinical relationship between disability and LOS. PMID- 7993165 TI - The Burke dysphagia screening test: validation of its use in patients with stroke. AB - The objective of this study was to validate a dysphagia screening test to identify patients in the rehabilitation phase post stroke at risk for pneumonia, recurrent upper airway obstruction, and death. The setting was an inpatient stroke rehabilitation unit. One hundred thirty-nine consecutive patients met the following criteria: stroke confirmed by clinical history and neurological exam with compatible computed tomography (CT) or magnetic resonance imaging (MRI) scan; ages 20 to 90 years inclusive; and no known history of significant oral or pharyngeal anomaly. The main outcome measures were pneumonia, recurrent upper airway obstruction, and death. The Burke Dysphagia Screening Test (BDST) identified 11 of 12 patients who subsequently developed pneumonia, recurrent upper airway obstruction, or death (Fisher's exact test: p = .03). The relative risk for the occurrence of any of these complications was 7.65 times greater for those failing versus passing the BDST. The BDST identified 9 of 9 patients who developed pneumonia (Fisher's exact test: p = .01). We concluded that the BDST is of value in identifying patients in the rehabilitation phase poststroke at risk for pneumonia, recurrent upper airway obstruction, and death. PMID- 7993167 TI - Inter-rater agreement and stability of functional assessment in the community based elderly. AB - The purpose was to examine the inter-rater agreement and test-retest stability of the Functional Independence Measure (FIM) and the Instrumental Activities of Daily Living Scale (IADL) from the Multidimensional Functional Assessment of Older Adults. These two instruments were administered to 20 older persons living in the community. Two experienced raters administered the assessment instruments over either a short (7-10 days) or long (4 to 6 week) interval. The intraclass correlation (ICC) was used to analyze the data. ICC values were computed for agreement between and within raters and across short and long intervals. ICC values for inter-rater agreement and stability ranged from 0.90 to 0.99. The relation between scores on the FIM and IADL scale was also examined. The analysis produced an r value of 0.85, suggesting a positive statistical relationship among the items assessed. The high ICC values indicate that the Functional Independence Measure Instrument and IADL scale of the Multidimensional Functional Assessment of Older Adults provide consistent information across two experienced raters and over time when used with a sample of elderly persons residing in the community. PMID- 7993168 TI - A randomized trial of identification bracelets to prevent falls among patients in a rehabilitation hospital. AB - This purpose of this study was to determine whether an identification bracelet is effective in preventing falls among high-risk patients who are undergoing in patient physical rehabilitation. A stratified, randomized, balanced controlled clinical trial was conducted; participants were blinded as to the outcome and the study hypothesis. All patients having one or more risk factors that predisposed them to falls were randomized to receive either a blue identification bracelet or no bracelet. The identification bracelet was intended to increase patients' vigilance about falling. Two risk strata were specified. The high risk stratum consisted of patients with stroke or ataxia, urinary incontinence, or a history of falls. The low risk stratum comprised patients older than 80 years and those on one or more medications that had been identified as contributing to an individual's risk of falling. This report presents the effect of the identification bracelet only among persons in the high-risk stratum. Over 1 year, 65 high-risk subjects were randomized to receive the blue identification bracelet and 69 high-risk subjects were controls. In the intervention group, 27 persons (41%) fell at least once, whereas in the control group 21 persons (30%) fell at least once yielding a hazard ratio of 1.3 (95% confidence interval: 0.8 to 2.4). These results suggest that the identification system was of no benefit in preventing falls among high-risk persons. PMID- 7993166 TI - Health-related information postdischarge: telephone versus face-to-face interviewing. AB - This study had two primary aims: (1) to determine the usefulness of a telephone administered health status questionnaire as an epidemiological survey instrument in groups at high risk for morbidity and disability; and (2) to evaluate the value of a telephone interview for making judgments about individual patient management. A structured telephone interview was compared with a face-to-face interview in 366 individuals with a stroke or an orthopedic condition up to 5 years after discharge from a rehabilitation hospital. Standardized assessments including the Barthel Index, the Zung Scale, the Reintegration to Normal Living (RNL) Index, and the Pfeiffer Short Portable Mental Status Questionnaire (SPMSQ), along with questions on health, medication use, and health events were administered using both modes. Comparability between the modes was also assessed according to the type of respondent, self, or proxy. On the Barthel Index, the Zung Scale, the RNL Index, and the SPMSQ the percentage of patients indicated as having no disability was similar between the modes. Proxies' responses were, in general, as consistent between the modes as patients' responses. The reliability coefficients indicated moderate to substantial agreement between the modes on the majority of indices and health-related questions. Discord between modes, when present, was greatest for individuals with moderate and severe disability, with less frequent reporting of disability on the telephone. This study supports the use of telephone interviews in determining the prevalence of disability in the community and supports the use of the telephone interview in the case finding process. PMID- 7993169 TI - Prosthetic profile of the amputee questionnaire: validity and reliability. AB - The Prosthetic Profile of the Amputee (PPA) is a clinical follow-up questionnaire that measures the factors potentially related to prosthetic use and the actual use of the prosthesis by people with a lower extremity amputation. This profile is a report on the psychometric properties of the questionnaire. The PPA was administered, on two occasions, to 89 adults with lower extremity amputations. Test-retest data analysis demonstrated that the questionnaire was reliable in terms of repeatability. Strong test-retest agreements were obtained. When the PPA was assessed against the Reintegration to Normal Living (RNL) index, results supported the presence of construct validity. Data confirmed convergence of analogous constructs of the PPA questionnaire and the RNL index and showed evidence of discrimination between the more distantly related constructs. Based on the results of this study, we conclude that the PPA questionnaire is reliable and valid for clinical and research use. PMID- 7993170 TI - Reliability of measuring isometric and isokinetic peak torque, rate of torque development, integrated electromyography, and tibial nerve conduction velocity. AB - To determine the reliability of measures used in neuromuscular diagnosis and rehabilitation, 23 adults underwent identical testing on two occasions. Intraclass correlation coefficients (ICC) showed the reliability of peak torque measurement to depend both on the movement tested and velocity of contraction (leg extension ICC = 0.64-0.94, plantar flexion ICC = 0.55-0.76, leg press ICC = 0.72-0.91). Peak rate of torque development (RTD) and the percentage of peak torque at peak RTD were not reliable for any movement (ICC = 0.02-0.28). Mean RTD between 30% and 60% of peak torque was unreliable for leg press (ICC = 0.46), yet fairly reliable for both knee extension (ICC = 0.61) and plantar flexion (ICC = 0.63). Mean integrated electromyography (IEMG) showed fair to good reliability for isometric and 1.05 rad.s-1 leg press (ICC = 0.66, 0.90, respectively), and plantar flexion and leg extension (ICC = 0.75-0.89). Tibial nerve conduction velocity was highly reliable (ICC = 0.89). A range of reliabilities can be expected when measuring these variables, and must be considered when interpreting neuromuscular data. PMID- 7993171 TI - Potentials associated with the Go/No-Go paradigm in traumatic brain injury. AB - Surface event-related potentials associated with visually triggered movements (Go) and the inhibition of planned movements (No-Go) were examined in seven healthy subjects and five postacute traumatic brain injured (TBI) subjects. Analysis showed that the cortical potential P1-N1 was similarly affected by condition in both the control and TB1 groups. Although TB1 subjects showed smaller P1-N1 amplitudes (Go = 2.91 uV; No-Go = 3.95 uV; p < .03) relative to control subjects (Go = 4.82 uV; No-Go = 6.03 uV; p < .03), both groups showed larger amplitudes in the No-Go condition. A bipolar lead (C3'-C3") over the sensorimotor cortex showed a reversal of polarity between Go and No-Go conditions which was synchronized with the EMG activity in all control subjects. This signal reversal and timing of potentials was absent in four of the five TB1 subjects' waveforms, suggesting difficulty in sensorimotor processes associated with movement control. In addition, TB1 subjects displayed a number of atypical stimulus-locked waveforms, which are discussed relative to the specific functional impairments of individual subjects. The results highlight the potential usefulness of such paradigms as the Go/No-Go procedure in the analyses of electroencephalographic waveforms and of the effects of TBI. PMID- 7993172 TI - Kinematics of wheelchair propulsion in adults and children with spinal cord injury. AB - This study examined the kinematic features of wheelchair propulsion in two neurologically matched groups of adults and children with uncomplicated spinal cord injury. The average mass and age of the pediatric group was much smaller than the adult group (37.4kg and 11.3 years vs 68.5kg and 33.5 years). Each subject propelled his/her own chairs and new, low-mass wheelchairs at a steady, nominal speed of 2 m/sec across a level surface. Three dimensional video analysis determined the movement of upper body angles (elbow, shoulder, trunk, and shoulder abduction) based on reflective markers placed on the subjects' shoulder, elbow, wrist, and hip joints. Analysis of the temporal factors showed that although the average group overground velocities of the adult group (2.4m/sec) were significantly greater than the pediatric group (2.3 m/sec), the two groups spent comparable proportions of the wheeling cycle in propulsion (24%). Analysis of the angular kinematics (elbow, shoulder, and shoulder abduction angular changes over a time normalized wheeling cycle) showed that whereas the pediatric group did show significant absolute angular differences from the adult group, the angular changes over time were the same in both groups. The implications of this work are that, for the first time, it can be said that children propel their wheelchairs in the same manner as adults. In addition, these data were similar to those previously reported in athletic adult populations. We conclude that published data from adult wheelchair users may be applied to pediatric wheelchair users, thus providing a basis for pediatric wheelchair prescription.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7993173 TI - Relation among indices of effort and oxygen uptake in below-knee amputee and able bodied children. AB - The purpose of this investigation was to determine the relationships among simple methods for measuring effort in below-knee amputee (BKA) and able-bodied (AB) children. Ten BKA children and 13 AB children walked on a treadmill and selected a freely chosen walking speed (CWS). Children then walked for 2 minutes at each of three speeds: CWS, 20% above CWS, and 20% below CWS. Oxygen uptake, heart rate, physiological cost index, percent maximum heart rate, and vertical displacement of a surface marker on the sacrum were determined for each subject and speed. Linear regression with repeated measures was used to determine correlations between oxygen uptake and the four variables (p < 0.05). To evaluate the effectiveness of the regression equations, two male children not part of the AB group were tested. The proportion of explained variance arising from the significant correlations between oxygen uptake and the four measured variables were all between 0.91 and 0.92. It was concluded that the vertical displacement of a marker on the sacrum is a simple and convenient measure for a biomechanics gait laboratory to estimate effort because only standard biomechanics laboratory equipment is required. Further, in a clinical setting and/or where the necessary equipment is available heart rate, physiological cost index, and percent maximum heart rate are also adequate. PMID- 7993174 TI - Cerebral aneurysms and arteriovenous malformations: implications for rehabilitation. AB - Arteriovenous malformations (AVM) and intracranial aneurysms often have devastating impact when they present as subarachnoid hemorrhage (SAH). With an overall incidence of 10 to 16 per 100,000, subarachnoid hemorrhage is relatively rare; however, these patients often comprise a significant component of a rehabilitation specialist's practice. There exists a host of risk factors and premorbid characteristics that correlate with long-term outcome after aneurysmal and AVM-related subarachnoid hemorrhage. Physical, cognitive, behavioral, and social deficits are relatively common after SAH, and can have a significant impact on effective home, community, and work reentry. Seizure risk after SAH or craniotomy and the use of prophylactic anticonvulsant medications is often a confusing and troublesome issue for the rehabilitation specialist. This situation often is handled by weighing the potential risk of serious medication side effects against the potential seizure risk. Cognitive, behavioral, and social sequelae are most frequent in patients with anterior cerebral and communicating artery lesions; however, delayed ischemic dysfunction often accounts for these deficits in patients with lesions in other distributions. An understanding of the classification, incidence, presentation, complications and treatment of arteriovenous malformations and intracranial aneurysms is especially important for the rehabilitation specialist. Knowledge about these areas assists the rehabilitation specialist in developing an individual rehabilitation plan that sets realistic goals for predicted outcomes. In addition, such knowledge enhances appropriate monitoring of patient progress, so that early interventions can be established when there is an alteration in clinical status. PMID- 7993175 TI - Rotator cuff tears. PMID- 7993176 TI - Outcomes evaluation in TBI Rehabilitation. Part I: overview and system principles. AB - Questions of how to measure outcomes are commonly heard in rehabilitation today. In this supplement we review the current state of the art of outcomes measurement in traumatic brain injury rehabilitation, discuss key issues, and identify steps that need to be taken. The underlying question is not simply that of outcomes measurement but how to infer effective and cost-effective treatment. The validity of such inferences rests on multiple features of the entire clinical information system. Requirements for valid, feasible, outcome-oriented clinical data systems are described. Effectiveness is inferred from variations in outcomes experienced by similar persons who received differing interventions. Outcome data systems need large sample sizes and technically adequate severity adjusters. A nationwide TBI data system is needed to identify reasonably homogeneous subgroups in different programs whose outcomes can be meaningfully compared. In alliance with payors and persons with disabilities, rehabilitation professionals can create outcome data systems that will provide the knowledge necessary to improve the effectiveness and cost-effectiveness of rehabilitation programs. PMID- 7993177 TI - Outcomes evaluation in TBI Rehabilitation. Part II: measurement tools for a nationwide data system. AB - In Part II we address tools for describing general functional levels of clients in acute care, in traumatic brain injury (TBI) rehabilitation programs, and in the community. Tools must be brief, have proven reliability, and measure characteristics common to moderately and severely brain-injured individuals. Possible components of a uniform dataset dedicated to TBI are described. PMID- 7993178 TI - Outcomes evaluation in TBI rehabilitation. Part III: Ethical perspectives and social policy. AB - The choice and interpretation of rehabilitation outcomes are suffused with personal and social values. In this article we examine the ethical implications of outcomes evaluation. The viewpoints of key parties to the rehabilitation process are considered. Self-determination of persons served is of central significance. Valuative conflicts in practice frequently obscure the meaning of a "good" outcome. Outcome studies can contribute to the development of a just policy but bear serious ethical responsibilities. Although these issues are general to rehabilitation, persons with TBI are at special risk of being disenfranchised. A new paradigm or clinical philosophy is needed to respond to the new and divergent pressures facing clinical rehabilitation. PMID- 7993179 TI - Three crises facing sexology. AB - Three crises facing sexology are described: what is happening with sexuality in the culture, what is happening with sexuality in academia, and what is happening with sexuality in medicine. In each case, the response of sexology has been benign neglect, disinterest, and a failure to understand the profound implications of these challenges for a field that considers itself the premiere source of accurate facts and comprehensive theories about sexuality. As a consequence we are losing control of our subject matter, and we are losing our professional legitimacy. A wake-up call is offered for sexologists to become more knowledgeable, for our paradigms and organizations to become more inclusive, and for our research methods to become more sophisticated. PMID- 7993180 TI - Sexual function in a community sample of middle-aged women with partners: effects of age, marital, socioeconomic, psychiatric, gynecological, and menopausal factors. AB - A randomly selected community sample of 436 women with partners was studied with regard to frequency of sexual intercourse and orgasm with their partners and to attitudes to their sexual relationships. Associations were examined between these factors and demographic, psychiatric, marital, gynecological, and menopausal status. Frequency of sexual intercourse, orgasm, and enjoyment of sexual activity with the partner were most closely associated with younger age and better general marital adjustment, with the partners' ages also appearing to influence frequency of sexual intercourse and the duration of the relationships to affect enjoyment of sexual activity. Women's satisfaction with their sexual relationships was most closely associated with marital adjustment and bore no relation to age. Weak positive associations were found between higher socioeconomic status and frequency of orgasm and enjoyment of sexual activity. Psychiatric factors (psychiatric disorder and neuroticism) made little contribution to differences in frequency of sexual activity although they were associated with attitudes towards it. Sexual behavior was largely unrelated to gynecological symptoms. Little difference was found between age-matched subgroups of pre- and postmenopausal women in frequency of sexual behavior and attitudes towards their sexual relationships. PMID- 7993181 TI - Menstrual cycle and work schedule: effects on women's sexuality. AB - Sexual interest and coital frequency reportedly fluctuate according to phases of the menstrual cycle, but attention has not been paid to factors such as wishes or fears regarding pregnancy or to the daily schedule of work vs. leisure time. With a view to simultaneous evaluation of the effects both of hormonal and social factors on sexual interest and activity, a group of women rated their level of sexual interest and frequency of coitus. Some variation in sexual interest and in the incidence of coitus during different menstrual phases was found. The incidence of coitus, however, was also affected by the work schedule with time off as a positive determinant. Present results are compared with those from a similar study of hysterectomized women in which the work schedule but not hormonal fluctuations of the ovarian cycle, influenced the likelihood of coitus. PMID- 7993182 TI - Is there a national standard with respect to attitudes toward sexually explicit media material? AB - Surveys in 10 states conducted with probability samples of adults (N = 4621) between 1976 and 1985 found that a statistically significant majority of the respondents in each state indicated acceptance of sexually explicit content in mass media. In each state, respondents felt that (i) standards have changed so that such material has become more acceptable; (ii) adults have the right to obtain such materials; and (iii) it is all right for adults to obtain and see materials containing exposure of the genitalia and every kind of sexual activity. Some factors contributing to what appears to be an emerging national consensus of acceptance are discussed. PMID- 7993183 TI - Intimacy and sexuality in gay male couples. AB - In a study of 320 men (20 to 77 years) in gay relationships, data were gathered on verbal, physical, and emotional intimacy and on sexual aspects of relationship functioning. Independent of relationship duration and partners' age, emotional intimacy predicts relationship satisfaction the best. Sexual satisfaction is best predicted by low sexual distance. Sexual frequency is best predicted by sexual satisfaction. Data analysis indicates that young gay men value emotional aspects of their relationship more than older gay men do. The attitude towards sexual encounters one partner has is related to his actual number of sexual partners and to his partner's attitude. PMID- 7993184 TI - Personality and lipid level differences associated with homosexual and bisexual identity in men. AB - Self-identified homosexual (n = 30), bisexual (n = 29), and heterosexual (n = 31) men were compared on measures of gender-typical behavior, sex role, ego strength, and lipid levels. Homosexual men differed significantly from the heterosexual men on the gender-typical behavior and feminine sex-role measure (both in adulthood and in childhood), and several trends and significant differences were found on the biochemical measures of lipid levels (especially when 7 obese men were removed from the analyses). As a rule, the bisexual men were different from the heterosexual men on the above measures, but were indistinguishable from the homosexual men. Bisexuals differed from both of the other two groups, however, by scoring lower on the ego strength scale and by reporting themselves to be more often troubled, lonely, and depressed. We caution that the lipid analyses were made on single blood samples and require an extended replication; however, we report the data because of their possible theoretical interest and because they replicate work of 20 years ago. PMID- 7993185 TI - The everyday experience of an institutionalized sex offender: an idiographic application of the experience sampling method. AB - The Experience Sampling Method (ESM) is a novel assessment strategy that allows random sampling of thoughts, affects, and behaviors. In ESM studies subjects wear beepers that signal at randomly generated, preprogrammed times at which subjects fill out a questionnaire containing items related to current activity, location, thought content, mood states, etc. The ESM was used to examine the relationship between mood states and thought content in a hospitalized sex offender. The patient exhibited a very high frequency of thoughts with sexual content, as well as thoughts indicative of anger against women, personal inadequacy, and distress. He appeared to be a poor judge of his state of optimal well-being. Whereas he considered support from others to be related to optimal well-being, it was actually sexual thoughts about a woman that were associated with his optimal well being. The present case study illustrates the value of the ESM in the study of complex thought-affect-behavior relationships. PMID- 7993186 TI - The prevalence and some attributes of females in the sadomasochistic subculture: a second report. AB - Nonprostitute women in the sadomasochism (S/M) subculture have been believed to be rare. A sample of 45 women from the S/M subculture of whom 34 were determined to be nonprostitutes was obtained. This sample is compared with a similar sample obtained by Breslow et al. (1985). Despite methodological differences between the present investigation and that of Breslow et al., interstudy similarities permit conclusions about women in the S/M subculture in addition to the fact that they occur with sufficient frequency to study. The women become aware of their orientation as young adults and most are satisfied with it. They tend to be better educated and less often married than the general population. A majority designate themselves as heterosexual but a substantial minority are bisexual. They tend more often to prefer the submissive role but preference for the dominant role or no preference are found with considerable frequency. Oral sex and bondage are favored activities. PMID- 7993188 TI - Hyperbaric oxygenation: is it an hepatic assist device? PMID- 7993187 TI - [44th general meeting of the Japanese Society of Allergology. Tokyo October 26 28, 1994. Abstracts]. PMID- 7993189 TI - Recirculation measures with urea and mannitol during hemodialysis. AB - A simple, accurate, and reproducible method of measuring recirculation in grafts during hemodialysis is essential for improving the efficiency of dialysis. In our studies, plasma samples for plasma urea nitrogen (PUN) were taken from the arterial line of the dialyzer at blood flows (A) of 200, 300, and 400 ml/min, preceded by a 5-min period of equilibration, and at 15 s and 2 min after turning the flow down to 100 ml/min (S), the latter serving as systemic samples. Recirculation was calculated as (S - A)/(S - V). Total blood flow (Qb) through the grafts was measured by color Doppler ultrasound. We found a significant, inverse relationship between recirculation and total flow through the graft at dialyzer Qb of 400 but not 300 or 200 ml/min. The magnitude and prevalence of recirculation was always greater when the 2 min sample was used as S compared to the 15 s sample and as dialyzer Qb increased. As a qualitative, urea-independent measure of recirculation, we assayed the appearance of mannitol in the arterial line in blood drawn 15 s after initiating a mannitol push into the venous line. Blood obtained just prior to the mannitol push was used as the zero blank. Thirteen of 18 patients had a measurable, but low, level of mannitol, 5 did not, and 2 had inconsistent results in studies done on separate days. We conclude that the majority of patients receiving chronic hemodialysis have a low degree of recirculation and that methods relying on urea must be suspected of exaggerating the true degree of recirculation. PMID- 7993190 TI - Differences in intravenous and subcutaneous application of recombinant human erythropoietin: a multicenter trial. AB - The aims of this clinical study were to compare the maintenance doses for intravenous (i.v.) and subcutaneous (SC) administration of recombinant human erythropoietin (rhEPO) and to investigate whether there is any difference in the increase of the packed cellular volume (PCV) per week under i.v. and SC administration of rhEPO from two production sites (Genetics Institute, Cambridge, USA; and Boehringer Mannheim, Penzberg, Germany). A total of 90 patients suffering from end-stage renal disease were included in the study. All patients had already been treated for at least 6 months with chronic hemodialysis. The study was carried out as a randomized, multicenter parallel group comparison study with a 1-week pretreatment phase, a subsequent 8-week double-blind phase, and a final open phase. The final open phase consisted of a correction phase and a maintenance phase. The production site had no influence on the PCV increase per week, and there were no differences with respect to tolerability. The median rhEPO dose required to maintain the target PCV of 30 to 35 vol.% was 33 U/kg body weight three times a week in the i.v. group compared with 22 U/kg in the SC group (i.e., an average of 30% less with SC administration). Development or aggravation of hypertension under rhEPO therapy was observed, especially during the correction phase and more frequently in the SC group than in the i.v. group. During the maintenance phase, there was no essential difference between the two groups. PMID- 7993191 TI - Improvement of hemocompatibility on a cellulose dialysis membrane with a novel biomedical polymer having a phospholipid polar group. AB - To improve surface hemocompatibility on cellulose hollow fibers for hemodialysis, newly designed hemocompatible polymers with a phospholipid polar group, 2 methacryloyloxyethyl phosphorylcholine (MPC) polymers, were introduced on the surface through two different methods: direct grafting of MPC on the surface, or coating of a water-soluble cellulose grafted with MPC. The MPC was polymerized using cerium ion as an initiator in the cellulose hollow fibers, and the poly(MPC) chains were grafted directly on the surface. Another modification of the cellulose hollow fibers was attempted by coating them with a water-soluble graft copolymer composed of a poly(MPC) side chain and a cellulose backbone. The coating process from an aqueous solution of the graft copolymer was very convenient, and the graft copolymer on the surface was not detached even after water circulated into the hollow fibers. These cellulose hollow fibers modified with MPC polymers displayed excellent hemocompatibility such as prevention of blood cell adhesion and aggregation after contact with blood without an anticoagulant. The permeability of the hollow fibers did not decrease as a result of these modifications. From these results, it is clearly suggested that introduction of the MPC units was effective for improving the hemocompatibility of the hollow fibers for hemodialysis. PMID- 7993192 TI - A one-step, operator-independent method for isolating islets of Langerhans from the porcine pancreas. AB - Large-scale isolation of islets of Langerhans is one of the major obstacles in islet transplantation. Until now, isolation methods relied on enzymatic digestion, the duration of which relies on a decision dictated by the operator's experience. This approach has always hindered development of an automated method. The aim of this study was to develop a one-step method based on complete digestion of the pancreas. The original aspect of the technique (derived from the Ricordi method) is use of the University of Wisconsin (UW) solution in the digestion medium and a continuous flow collagenase processing circuit with local cooling and rewarming to allow tissue digestion to proceed at 37 degrees C while settling of the cell suspension takes place at 4 degrees C. A stopcock system permits the alternate use of two settling chambers so that while one is in the circuit, the other can be removed for centrifugation, resuspension of the crude islet preparation in collagenase in free UW solution, and further purification in a density gradient system. Ten experiments were performed, and 545,750 +/- 48,670 purified pig islets were obtained per totally digested pancreas. Histological studies showed cell integrity. Insulin secretion in response to double glucose stimulation under perfusion conditions demonstrated the functional viability of the isolated islets. In conclusion, this one-step method makes it possible to obtain a high number of viable islets of Langerhans in the absence of any decision by an operator, and it should therefore provide basis for an automated method. PMID- 7993193 TI - Life-saving effect of pyridoxalated hemoglobin-polyoxyethylene conjugate on carbon monoxide intoxication of rabbits. AB - We examined whether pyridoxalated hemoglobin-polyoxyethylene conjugate (PHP) could be life-relievable for carbon monoxide (CO) intoxication. Toxic gas (O2, 5.0%; CO2, 16.0%; CO, 1.8%; and N2, 77.2%) was inhaled by rabbits anesthetized with urethane and the following parameters were measured: blood pressure, arterial and venous Po2, Pco2, pH, and carboxyhemoglobin (COHb). When mean blood pressure reached 0 or 20 mm Hg as an index after inhalation of the toxic gas, the toxic gas was switched to air; intravenous infusion of physiological saline or PHP (1.2 g/20 ml/kg/30 min) was simultaneously initiated. In the experiment using 0 mm Hg blood pressure, PHP prolonged the survival time and exhibited significant temporary recovery of P02 and Pco2 in comparison with saline. In the experiment using the 20 mm Hg blood pressure, a significant difference in each parameter was observed between the saline and PHP groups. Two of 8 animals in the saline group died without any recovery of each parameter. All 6 animals in the PHP group survived and each parameter recovered. PHP accelerated recovery from high COHb concentrations, low arterial and venous Po2, reduction of arterial and venous Pco2, and elevations of pH and blood pressure. These results suggest that PHP treatment during the early stage of CO intoxication is life-saving and effective in facilitating the recovery of various functions. PMID- 7993194 TI - In vitro evaluation of platelet/biomaterial interactions in an epifluorescent video microscopy combined with a parallel plate flow cell. AB - Suitable evaluation systems are critical for ranking various biomaterials in order to develop a method to design and synthesize nonthrombogenic biomaterials. We have recently developed an in vitro test system to evaluate platelet/biomaterial interactions in whole blood. The system consists of a parallel plate flow cell and epifluorescent video microscopy (EVM). A glass coverslip coated with a polymer was incorporated into the flow cell, and blood was perfused using a syringe pump via a polymer-coated PVC tubing connected to the flow cell. Whole human blood was anticoagulated with heparin (2 U/ml), and the platelets were labeled with the fluorescent dye mepacrine (5 microM). This system permitted real-time and dynamic observations of platelet/biomaterial interactions in whole blood under a defined flow condition. In order to evaluate the feasibility of this system, two different segmented polyether-polyurethanes (SPEUs), PU-PTMG(650) and PU-PTMG(2000), were chosen as test polymers. Surface characteristics verified with electron spectroscopy for chemical analysis (ESCA) and contact angle measurements showed similar results in both SPEUs. Blood was perfused at a wall shear rate of 200 s-1 for 20 min. Excitation light was applied for 2 s at 1 min intervals. The real-time image was then analyzed at each time point for the percentage of surface area of platelet coverage. Plasma beta thromboglobulin (beta-TG) levels were also measured before and after each run. PU PTMG(650) showed a significantly higher number of adhered platelets than PU PTMG(2000) at each time point.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7993195 TI - Oversaturation status of reticuloendothelial system following cardiopulmonary bypass. AB - In the past, it was generally believed that the phagocytic function of the reticuloendothelial system (RES) was depressed after cardiopulmonary bypass (CPB), but several investigators reported differing results. Therefore, this study was performed to determine the effect of CPB on RES function, experimentally and clinically. Six dogs undergoing CPB (CPB group) were compared with an identical number of dogs subjected to thoracotomy without CPB (control group). A lipid emulsion test was performed in all dogs before and after the surgical procedure to measure RES phagocytic function. Any ultrastructural changes in Kupffer cells were observed by electron microscopy. In both groups, the RES phagocytic index showed a significant decline after surgery. However, comparison of the 2 groups revealed that there was a significantly greater decrease in the CPB group (p < 0.05). Electron microscopy of the Kupffer cells showed that the number of phagosomes, especially those containing deformed erythrocytes, increased after CPB. Twenty patients undergoing cardiac surgery requiring CPB (Group A) and 8 patients undergoing pulmonary resection (Group B) were studied. RES phagocytic function was determined 3 days prior to surgery and 3 days postoperatively using the lipid emulsion test. No significant difference was observed in the preoperative phagocytic indices between the 2 groups. The phagocytic function remained almost unchanged in Group A on the third postoperative day, compared with the preoperative value, but it increased significantly in Group B on the third postoperative day, compared with the preoperative value. The intergroup difference was significant on the third postoperative day (p < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7993196 TI - Novel method to determine instantaneous blood volume in pulsatile blood pump using electrical impedance. AB - A novel real-time volumetric method was developed for a pulsatile pump. This method, the impedance method, used electrical impedance change in the blood chamber according to volume change while pumping. This method was evaluated with two kinds of air-driven diaphragm pumps. During in vitro tests, the impedance method indicated real-time volume change, and there was excellent correlation between computed stroke volume with the impedance method and measured stroke volume with the electromagnetic flowmeter. In chronic animal tests with goats and in a clinical case, the impedance method measured pump output accurately, and it detected diaphragm motion in real-time. In addition, excellent durability was seen. Full-fill to full-empty drive was realized accurately with this method. Application of the impedance method was easy, and it did not deteriorate native antithrombogencity of the pump. The impedance method is practical and useful to estimate the pumping condition of a pulsatile blood pump, especially a diaphragm pump. This method would be useful in clinical application. PMID- 7993198 TI - Keratocyte loss after corneal deepithelialization in primates and rabbits. PMID- 7993197 TI - Culture of a differentiated liver cell line, Hep G2, in serum with application to a bioartificial liver: effect of supplementation of serum with amino acids. AB - Much effort has been directed toward the development of serum-free, hormonally defined culture conditions for the maintenance of differentiated functions in many cell types, including hepatocytes. However, in the development of a hepatocyte bioreactor for artificial liver support, many designs propose the maintenance of cells in plasma as opposed to defined culture medium. There is very little reported literature on the growth and function of cells cultured in plasma or serum; therefore, the effect of increasing serum concentrations was investigated using the human hepatoma, Hep G2, as a model cell line. It was found that Hep G2 can survive and grow in 100% serum if the serum is supplemented with L-glutamic acid, glycine, and L-cysteine. PMID- 7993199 TI - Comparison of excimer laser treatment of astigmatism and myopia. PMID- 7993200 TI - The $94250 bottle of eyedrops. PMID- 7993201 TI - Infectious keratitis 1 day after radial keratotomy. PMID- 7993202 TI - Perforated bacterial corneal ulcer in a radial keratotomy incision secondary to minor trauma. PMID- 7993204 TI - Differentiating zosteriform herpes simplex from ophthalmic zoster. PMID- 7993203 TI - Complications of automated lamellar keratectomy. PMID- 7993205 TI - Hermann von Helmholtz: a century later. PMID- 7993206 TI - The socioeconomic aspects of laser refractive surgery. AB - Excimer laser photorefractive keratectomy (PRK) has shown promising results in preliminary studies. However, even if long-term safety and efficacy are demonstrated, questions have been raised about its viability from a cost effectiveness perspective. We analyzed the economic investment of elective excimer laser PRK both from the societal and individual perspectives. When the present value of likely expenses associated with excimer laser PRK and follow-up care are compared with those entailed in wearing soft contact lenses, PRK is roughly equivalent to daily wear soft contact lenses over a 10-year horizon and considerably less expensive than extended-wear soft contact lenses. When the analytic perspective is extended to 20 years, excimer laser PRK is a less expensive investment than both daily wear and extended-wear soft contact lenses. PMID- 7993208 TI - Surgical results of trabeculotomy ab externo for developmental glaucoma. AB - OBJECTIVE: To elucidate long-term surgical outcome of trabeculotomy ab externo in the treatment of developmental glaucoma. PATIENTS: Included in this retrospective study are 116 eyes of 71 patients with developmental glaucoma. We classified patients into three groups based on their age: congenital (33 eyes), existing before age 2 months; infantile (31 eyes), occurring from ages 2 months to 2 years; and juvenile (52 eyes), age 2 years or older. RESULTS: A life-table analysis showed that the total success probabilities at 5 and 10 years with one or more trabeculotomy ab externo operations were, respectively, 92.5% +/- 2.7% and 76.5% +/- 6.2%. The success probability of patients with congenital glaucoma (60.3% +/- 15.9%) was significantly lower than it was for those with infantile (96.3% +/- 3.6%) or juvenile (76.4% +/- 7.5%) glaucoma (P < .01 for both). CONCLUSIONS: Surgical results of trabeculotomy ab externo remain effective for a long time. Congenital glaucoma has the worst prognosis, and infantile glaucoma has a better prognosis than does juvenile glaucoma. PMID- 7993207 TI - Treatment of cytomegalovirus retinitis with an intraocular sustained-release ganciclovir implant. A randomized controlled clinical trial. AB - BACKGROUND AND METHODS: We performed a randomized controlled clinical trial to assess the safety and efficacy of a 1 microgram/h ganciclovir implant for the treatment of newly diagnosed cytomegalovirus (CMV) retinitis in patients with the acquired immunodeficiency syndrome (AIDS). Patients with previously untreated peripheral CMV retinitis were randomly assigned either to immediate treatment with the ganciclovir implant or to deferred treatment. Standardized fundus photographs were taken at 2-week intervals and analyzed in a masked fashion. The study end point was progression of retinitis based on the photographic assessment. RESULTS: Twenty-six patients (30 eyes) were enrolled. The median time to progression of retinitis was 15 days in the deferred treatment group (n = 16) vs 226 days in the immediate treatment group (n = 14) (P < .00001, log-rank test). During the study, 39 primary implants and 12 exchange implants were placed in immediate-treatment eyes, deferred-treatment eyes that progressed, or contralateral eyes that developed CMV retinitis. Postoperative complications in the total series included seven late retinal detachments and one retinal tear without detachment. Final visual acuity was 20/25 or better in 34 of 39 eyes. The estimated risk of developing CMV retinitis in the fellow eye was 50% at 6 months. Biopsy-proven visceral CMV disease developed in eight (31%) of 26 patients. The median survival was 295 days. CONCLUSION: The ganciclovir implant is effective for the treatment of CMV retinitis. Patients with unilateral CMV retinitis treated with the implant are likely to develop CMV retinitis in the fellow eye, and some patients will develop visceral CMV disease. PMID- 7993209 TI - Results of surgical treatment of recent-onset full-thickness idiopathic macular holes. AB - OBJECTIVE: To investigate whether the visual prognosis after macular hole surgery was different between recent and older holes and to evaluate preoperative characteristics and variations in surgical technique that may influence outcome. DESIGN: The medical charts of all our patients who underwent surgery for a full thickness macular hole were retrospectively reviewed. PATIENTS: Forty-eight eyes of 48 patients in the "early" group (symptoms < or = 6 months), and 20 eyes of 19 patients in the "late" group (symptoms > 6 months). INTERVENTION: Vitrectomy, separation of the posterior hyaloid, gas tamponade, and instructions to be face down for 1 week. Most patients had epiretinal membrane dissection. MAIN OUTCOME MEASURES: The early and late groups were compared regarding anatomic and visual outcomes. In the early group we evaluated the effect on outcome of the stage of the hole, intraocular tamponade, membrane dissection, and travel distance. RESULTS: Median postoperative visual acuity in the early group was 20/40 at 3, 6, and 12 months. Fifteen (56%) of 27 patients gained at least three lines of vision at 12 months. Anatomic success was seen with one operation in 75% (36/48), and with two operations in 87.5% (42/48). Stage 2 holes had a final anatomic success rate of 94.4%. Of respondents to an informal survey, 63.4% (26/41) believed that vision was greatly improved, and 70.3% (26/37) said that they would definitely choose surgery again. In the late group, median postoperative visual acuity was 20/100 at 6 months, compared with 20/142 preoperatively. Closure of the hole with one operation was seen in 60% (12/20) of the patients in the late group. CONCLUSIONS: Surgery in patients with recent macular holes has a better prognosis for visual rehabilitation than with older holes and appears to be considered beneficial by most patients. PMID- 7993210 TI - Comparison of flow cytometry with the surgeon regarding ability to predict the ultimate success of surgery for proliferative vitreoretinopathy. AB - OBJECTIVE: To analyze vitreous specimens obtained from human eyes with proliferative vitreoretinopathy (PVR) by use of flow cytometery (FC) to compare the capacity of FC with that of the surgeon's in predicting the ultimate outcome after PVR surgery. METHODS: Thirty-one vitreous aspirates were obtained at vitrectomy or from postoperative fluid-gas exchanges for complicated retinal detachment due to PVR. Samples were analyzed by FC for the concentration of total and proliferating cells. These measurements were compared with the surgeon's preoperative prognosis (good, poor, or indeterminate) for the ultimate result. At 12 weeks, the eyes were evaluated for clinical outcome. An unsuccessful outcome was one in which the retina was attached with macular pucker or hypotony or was anatomically detached. Anatomic attachment of the retina anterior and posterior to the scleral buckle without these findings was considered a successful outcome. RESULTS: Flow cytometry was capable of quantifying the concentration of total and proliferating cells in eyes with PVR. Eyes destined for an ultimately successful outcome demonstrated fewer total and proliferating cells than did eyes destined for an unsuccessful outcome. No differences were observed between eyes destined for development of macular pucker and those destined for anatomic redetachment. The surgeon was able to accurately predict a good or a poor outcome in 64.5% of the cases, with a sensitivity of 92% and a specificity of 89%. Using the total number of recovered cells, FC was able to correctly predict a good or a bad outcome with a 77% accuracy, whereas the surgeon was able to do so with a 65% accuracy. Combining the surgeon's prediction with the result of FC increased the diagnostic power of the prediction to 87%. CONCLUSIONS: The diagnostic power of FC was similar to that of the surgeon's in predicting ultimate outcome, but the two techniques probably evaluate different features of the disease process. The combination of the two techniques was the most powerful approach to the prediction of ultimate outcome after PVR surgery. PMID- 7993211 TI - Ocular findings in patients with autosomal dominant retinitis pigmentosa and transversion mutation in codon 244 (Asn244Lys) of the peripherin/RDS gene. AB - OBJECTIVE: To identify phenotypic characteristics of a certain mutation in the peripherin/RDS gene. DESIGN: Case reports with clinical features and results of fluorescein angiography, electroretinography, kinetic visual field testing, dark adaptometry, and DNA analysis. SETTING: University medical center. PATIENTS: We studied the ocular findings in eight members of a Japanese family with autosomal dominant retinitis pigmentosa and cytosine-to-adenine transversion at the third nucleotide in codon 244 of the peripherin/RDS gene. This mutation resulted in a substitution of lysine for asparagine in amino acid 244 of peripherin/RDS, a photoreceptor-specific glycoprotein. RESULTS: Clinical findings of each affected member in this family showed a marked intrafamilial similarity, which may provide the natural course of the phenotype produced by the Asn244Lys mutation. Characteristic features include diffuse pigmentary retinal degeneration in the midperipheral and peripheral fundi associated with macular degeneration in the later stage, starting with bull's-eye maculopathy, and severely deteriorated electroretinographic findings in both rods and cones, even in the early stage. CONCLUSION: The mutation at codon 244 of the peripherin/RDS gene causes both rod and cone degeneration, although the precise mechanism of retinal degeneration is currently unknown. PMID- 7993212 TI - Ocular findings associated with a Cys39Arg mutation in the Norrie disease gene. AB - OBJECTIVE: To diagnose the carriers and noncarriers in a family affected with Norrie disease based on molecular analysis. DESIGN: Family members from three generations, including one affected patient, two obligate carriers, one carrier identified with linkage analysis, one noncarrier identified with linkage analysis, and one female family member with indeterminate carrier status, were examined clinically and electrophysiologically. Linkage analysis had previously failed to determine the carrier status of one female family member in the third generation. Blood samples were screened for mutations in the Norrie disease gene with single-strand conformation polymorphism analysis. The mutation was characterized by dideoxy-termination sequencing. RESULTS: Ophthalmoscopy and electroretinographic examination failed to detect the carrier state. The affected individuals and carriers in this family were found to have a transition from thymidine to cytosine in the first nucleotide of codon 39 of the Norrie disease gene, causing a cysteine-to-arginine mutation. Single-strand conformation polymorphism analysis identified a patient of indeterminate status (by linkage) to be a noncarrier of Norrie disease. CONCLUSION: Ophthalmoscopy and electroretinography could not identify carriers of this Norrie disease mutation. Single-strand conformation polymorphism analysis was more sensitive and specific than linkage analysis in identifying carriers in this family. PMID- 7993213 TI - Independence of optokinetic nystagmus asymmetry and binocularity in infantile esotropia. AB - OBJECTIVE: Children with congenital esotropia, amblyopia, or early visual deprivation have persistent asymmetric monocular pursuit, as measured by optokinetic nystagmus (OKN), and favor targets moving in a temporal to nasal direction. Previous studies suggest that binocular visual development is necessary for the development of symmetric monocular OKN. We recently treated patients with congenital esotropia with unconventionally early surgery to establish good binocularity. We wished to determine if mature symmetric OKN responses could develop in patients with congenital esotropia following the acquisition of good stereopsis. METHODS: Electro-oculographic recordings documented horizontal eye movements in response to an electronic OKN stimulus. PATIENTS: The recordings of three patients with congenital esotropia that had been surgically aligned before age 20 weeks and who had achieved high-grade stereopsis with random dot and Titmus stereographic testing were studied. We compared this group of children with groups of age-matched controls, including the following: (1) three patients with congenital esotropia who underwent surgical alignment after age 6 months and who had no amblyopia but poor stereopsis; (2) three children with accommodative esotropia, good ocular alignment when wearing spectacles, and good stereopsis; and (3) three normal children. RESULTS: The normal children and those with accommodative esotropia demonstrated normal symmetrical OKN. The patients with congenital esotropia showed poor nasal to temporal OKN regardless of the degree of stereopsis or timing of surgery. CONCLUSIONS: Our results indicate that good binocularity, as measured by stereopsis, is not sufficient for the development of symmetric OKN in patients with congenital esotropia. PMID- 7993214 TI - Micrometer-scale resolution imaging of the anterior eye in vivo with optical coherence tomography. AB - OBJECTIVE: To demonstrate a new diagnostic technique, optical coherence tomography, for high-resolution cross-sectional imaging of structures in the anterior segment of the human eye in vivo. Optical coherence tomography is a new, noninvasive, noncontact optical imaging modality that has spatial resolution superior to that of conventional clinical ultrasonography (< 20 microns) and high sensitivity (dynamic range, > 90 dB). DESIGN: Survey of intraocular structure and dimension measurements. SETTING: Laboratory. PATIENTS: Convenience sample. MAIN OUTCOME MEASURES: Correlation with range of accepted normal intraocular structure profiles and dimensions. RESULTS: Direct in vivo measurements with micrometer scale resolution were performed of corneal thickness and surface profile (including visualization of the corneal epithelium), anterior chamber depth and angle, and iris thickness and surface profile. Dense nuclear cataracts were successfully imaged through their full thickness in a cold cataract model in calf eyes in vitro. CONCLUSIONS: Optical coherence tomography has potential as a diagnostic tool for applications in noncontact biometry, anterior chamber angle assessment, identification and monitoring of intraocular masses and tumors, and elucidation of abnormalities of the cornea, iris, and crystalline lens. PMID- 7993215 TI - Periocular granuloma annulare, nodular type. Occurrence in late middle age. AB - We describe the two oldest individuals with nodular granuloma annulare (pseudorheumatoid nodules) in the ophthalmologic literature and propose a unified classification scheme that recognizes pseudorheumatoid nodules to be granuloma annulare, nodular type. All lesions in both cases revealed so-called necrobiotic granulomas, characterized by an acellular central area containing mucin (hyaluronic acid) surrounded by palisading histiocytes (macrophages), diagnostic of granuloma annulare. These features are identical to those reported in the ophthalmologic and older general pathology literature as pseudorheumatoid nodules and the contemporary general and dermatologic pathology literature as granuloma annulare. We believe the diagnosis of nodular granuloma annulare should be employed for necrobiotic lesions displaying distinctive clinicopathologic features to unite the ophthalmologic, general, and dermatologic pathology literature. Granuloma annulare, nodular type, must also be considered in the differential diagnosis of ocular and periocular lesions at any age. PMID- 7993216 TI - A clinicopathologic report of the retinal lesions associated with didanosine. AB - Didanosine, a purine analogue with antiretroviral activity, is used in the treatment of human immunodeficiency virus disease. Associated toxic effects of didanosine include pancreatitis, peripheral neuropathy, and retinopathy. The retinal lesions associated with didanosine therapy were studied in a 6-year-old girl with acquired immunodeficiency syndrome. Gross examination disclosed multiple well-circumscribed depigmented lesions in the midperipheral retina. Microscopic examination of these lesions showed multiple areas of retinal pigment epithelial (RPE) loss, some surrounded by areas of hypertrophy or hypopigmentation of the RPE. Partial loss of the choriocapillaris and neurosensory retina were also noted in areas of diseased RPE. Transmission electron microscopy showed numerous membranous lamellar inclusions and cytoplasmic bodies in the RPE cells. These data show that didanosine primarily affects the RPE and that the choriocapillaris and overlying neurosensory retina are also dystrophic in areas of RPE loss. PMID- 7993217 TI - Detection of herpes simplex viral DNA in the iridocorneal endothelial syndrome. AB - OBJECTIVE: To test the hypothesis that the iridocorneal endothelial (ICE) syndrome has a viral origin by comparing the incidence of viral DNA in corneal specimens from patients with the ICE syndrome and from controls. DESIGN: Thirty one corneas obtained from 25 patients with the ICE syndrome and six with chronic herpetic keratitis (n = 31) were compared with 30 control specimens obtained from 15 healthy donors and from 15 patients with other, nonviral chronic corneal diseases. METHODS: Primer pairs and polymerase chain reaction methods were used to identify and amplify either a segment of the DNA polymerase gene in the case of the herpes simplex and zoster viruses or a region of the nuclear antigen gene for the Epstein-Barr virus. The oligonucleotide amplified by polymerase chain reaction was fully characterized with the use of restriction enzyme, hybridization, and sequence analyses to determine that it contained the expected base pair sequence. RESULTS: Sixteen of 25 ICE syndrome specimens and four of six herpetic keratitis specimens were positive for herpes simplex virus (HSV) DNA. All nine ICE syndrome specimens tested were negative for the presence of DNA from the herpes zoster or the Epstein-Barr viruses. Controls were uniformly negative for HSV DNA whether they were obtained from ostensibly normal corneas (n = 15) or from corneas with intestinal keratitis, aphakic bullous keratopathy, or keratoconus (n = 15). Tissue samples cut from positive ICE syndrome specimens yielded negative results when retested after the endothelial layer was removed. These findings indicate that localization of HSV DNA is within the endothelium, the tissue primarily involved in the pathogenesis of the ICE syndrome. CONCLUSIONS: Polymerase chain reaction evidence shows that HSV DNA is present in a substantial percentage of ICE syndrome corneal specimens and that HSV-DNA is absent in normal corneas and in corneas from patients with three other chronic corneal diseases. These results provide direct evidence to support our hypothesis that the ICE syndrome has a viral origin. We discussed clinical implications, including possible therapeutic interventions. PMID- 7993219 TI - Unusual penetrating intraorbital foreign body. PMID- 7993218 TI - Phalloidin inhibits epinephrine's and cytochalasin B's facilitation of aqueous outflow. AB - OBJECTIVE: To determine whether phalloidin, a fungal peptide that inhibits actin filament depolymerization, could inhibit the ability of cytochalasin B and epinephrine to increase the facility of aqueous outflow in the eyes of living cynomolgus monkeys. METHODS: Outflow facility was determined by two-level constant-pressure perfusion of the anterior chamber. After measurement of baseline facility in both eyes, one eye of each animal received intracameral phalloidin (1.3, 13, or 130 mumol/L); the opposite eye received vehicle. Both eyes then received either epinephrine (0.3 mmol/L) or cytochalasin B (0.2 mmol/L), and facility was again measured. RESULTS: Cytochalasin B and epinephrine increased facility by 120% to 190% and 100% to 180%, respectively (uncorrected for 15% resistance washout caused by perfusion itself). Phalloidin itself (13 or 130 mumol/L) did not affect facility, but it inhibited up to 50% of the facility increasing effect of cytochalasin B and epinephrine. CONCLUSIONS: We conclude that (1) the aqueous humor outflow facilitating effects of cytochalasin B or epinephrine depend in some manner on depolymerization of actin filaments within trabecular meshwork cells, and (2) actin filaments may help regulate aqueous outflow. PMID- 7993220 TI - Intrascleral foreign body simulating extrascleral extension of uveal melanoma. PMID- 7993221 TI - Subretinal hemorrhage precedes development of angioid streaks. PMID- 7993222 TI - Cellulose sponge punch for controlled mitomycin application. AB - We describe a new punch for cellulose sponges that helps to standardize the application of mitomycin during glaucoma filtration surgery. The punch was used to create 40 cellulose application disks. The height, diameter, and weight were measured in both wet and dry states. The disk dimensions and weights were reproducible, with a coefficient of variation less than 5 for all categories. The punch has been very useful in our clinical practice and research. PMID- 7993223 TI - Immunohistopathological investigation on unspecific chronic sclerosing sialadenitis of the submandibular gland (Kuttner tumor). AB - An immunohistochemical investigation was conducted on infiltrating lymphocytes in submandibular glands removed from three cases with unspecific chronic sclerosing sialadenitis of the submandibular gland (unspecific CSSS) which has been described for the first time by Kuttner. A high degree of lymphocyte infiltration was recognized and formation of lymphatic follicles was observed. In particular, activated B cells were predominantly observed in that part of the lymphatic follicles which was equivalent to germinal centers. In the T cell subset, the helper/inducer T cells displayed significant dominance over suppressor/cytotoxic T cells, and were distributed in the dark peripheral zone of the follicles. The distribution pattern of these lymphocytes seemed to be similar to antigenically stimulated lymph nodes and it was recognized that the unspecific CSSS could be a site of exceedingly active local immune responses. The authors believe that these findings support the view that unspecific CSSS (Kuttner tumor) is an immune disorder. PMID- 7993224 TI - A case of cerebellar infarction occurred with the 8th cranial nerve symptoms. AB - A rare case, 32-year-old man, of cerebellar infarction with the occurrence of the 8th cranial nerve symptoms was reported. On the neuro-otological examination, hearing test and caloric test showed a severe hearing loss and no response on the right side, respectively, and the spontaneous horizontal nystagmus fixed to the left direction was observed. Magnetic resonance (MR) imaging showed the infarctions in the areas of anterior inferior cerebellar artery (AICA) and posterior inferior cerebellar artery (PICA) on the right side. On the 14th illness day, the 8th cranial nerve symptoms disappeared, and on the 12th illness day, right hearing level and caloric response were significantly improved. We suggested that such an early recovery of the subjective symptoms and neuro otological findings may be attributable to the recanalized circulation disturbance or the development of collateral circulation. PMID- 7993225 TI - Electronystagmographic findings in a case of Lermoyez's syndrome. AB - A 40-year-old female patient with Lermoyez's syndrome is presented. Prior to the vertiginous attack, right low-tone hearing loss and tinnitus were noted. During the vertiginous attack, spontaneous nystagmus was directed to the right (lesioned) side, with improvement of cochlear symptoms. After the vertiginous attack, nystagmus was positional rather than spontaneous, and was directed to the left (opposite) side, with the subsidence of cochlear symptoms. One week later, follow-up audiometry revealed bilateral normal hearing. PMID- 7993227 TI - Primary small cell carcinoma of the larynx. AB - Small cell carcinoma is a rare tumor of the larynx. We present such a case in a 78-year-old female. The histopathological diagnosis at the time of laryngomicroscopic biopsy was squamous cell carcinoma, upon which basis we initially chose surgical treatment. The surgical specimen, however, revealed small cell carcinoma. Despite the administration of radiotherapy and chemotherapy, the patient died 9 months after initial presentation. We believe that this case illustrates the need for a sufficiently large biopsy specimen in order to arrive at the correct histopathological diagnosis when small cell carcinoma of the larynx is present, and that immunohistochemistry and electron microscopy should be performed to aid the diagnosis. PMID- 7993226 TI - Preoperative embolization for paraganglioma. AB - We have applied a new method of preoperative embolization to an intravagal and to carotid body paraganglioma, using estrogen dissolved in absolute alcohol and polyvinyl alcohol particles, which diffusely embolizes vessels from capillaries to main feeders. Total resection of the tumors after embolization was successively performed without postoperative complications; total blood loss was 205 and 130 ml, respectively, and the surgical time was approximately 3 hours in both cases. The technique, characteristics, and advantages of this method are discussed. PMID- 7993228 TI - Two cases of head and neck cancer with carotid artery reconstruction. AB - A carotid artery reconstruction was performed on two patients of head and neck cancer with infiltration into the carotid artery. To detect any possibility of cerebral ischemia at the time of ligation of the carotid artery, a temporary occlusion test of the internal carotid artery with a balloon catheter (balloon Matas test) was performed in both cases. An artificial vessel (Case 1) and a greater saphenous vein (Case 2) were used as an implanted vessel. No neurological sequelae were observed during or after the surgery in these cases. With a recent advance in various imaging diagnosis and an improvement in surgical techniques, the radical treatment including carotid artery reconstruction is expected to improve the prognosis for the cases demonstrating tumor infiltration into the carotid artery. PMID- 7993229 TI - Tympanoplasty with reconstruction of soft posterior meatal wall in ears with cholesteatoma. AB - A surgical technique for the reconstruction of a posterior meatal wall using a soft material (fascia) was developed for ears with cholesteatoma. Both myringoplasty and reconstruction of the posterior meatal wall were simultaneously performed using a large sheet of fascia, after the removal of the posterior meatal bony wall and the lesion. Even if postoperative middle ear aeration is disturbed, a retraction pocket may be expected to occur easily in ears with a soft posterior meatal wall, because of its flexibility compared to ears with a usual hard posterior meatal wall. This method is simple and can be useful in ears in which the posterior bony wall is removed. PMID- 7993230 TI - Effects of arterial occlusion on endocochlear DC potential and cochlear blood flow in guinea pigs. AB - The present study was undertaken to investigate the role of collateral arteries in cochlear circulation by examining the effect of occlusion of branches of the basilar artery on endocochlear DC potential (EP) and cochlear blood flow (CBF). EP and CBF were measured at the basal turn of the cochlea during microclamp occlusion of the basilar artery, its branches and the posterior inferior cerebellar artery (PICA). CBF was measured with a laser Doppler flowmeter. Systemic blood pressure (SBP) increased at occlusion of the basilar artery, but was not influenced by any occlusion of its branches. Changes of EP and CBF at occlusion of the basilar artery were classified into two types: recovery type and non-recovery type. Thirty-five guinea pigs were classified into three groups according to the number of branches of the basilar artery: Group A with one branch in 10 animals (29%), Group B with two branches in 20 animals (57%), and group C with three branches in 5 animals (14%). From the results obtained at successive occlusions of branches of the basilar artery and PICA, it is clear that the anterior inferior cerebellar artery (AICA) supplies blood to the cochlea more or less in all animals, although the reduction of the blood volume by its occlusion is not enough to decrease EP in some animals. When vascular dysfunction occurs in AICA of such animals, other branches of the basilar artery and/or PICA will play an important role to maintain cochlear circulation. PMID- 7993231 TI - Cytoskeletal organization of the vestibular sensory epithelia: saponin perfusion method for observing intracellular structures by scanning electron microscopy. AB - The cytoskeletal organization of the guinea pig vestibular sensory epithelial cells were investigated by the use of saponin perfusion method using scanning electron microscopy. The skeletal framework of a cell is composed of thin (actin or intermediate filaments) and thick filaments (microtubules). The membrane bound organelles such as nucleus, mitochondria, endoplasmic reticulum, Golgi apparatus, etc. were also well demonstrated. This made it possible to investigate the three dimensional structures of cytoskeletons as well as their complex interactions with various membranes bound organelles. It is therefore suspected that this technique may provide us further information about distribution, topographic relationships, and the functional role of cytoskeletons. PMID- 7993233 TI - Cochlear implantation: preoperative counselling and postoperative problems. AB - Some patients cannot understand the reasons for a cochlear implant, nor the implications of such a device, and thus a clear explanation is required during patient counselling. Approximately one tenth of the patients with hearing loss examined in our hospital have received cochlear implants. Adequate preoperative examinations can make the surgery less difficult. Following cochlear implantation, speech comprehension of the patients with prelingual hearing loss is poor, and even patients with good speech comprehension have complaints about the clarity of the voice by the cochlear implant. PMID- 7993232 TI - The transitional region of the eighth nerve in elderly humans: light and electron microscopic study. AB - To investigate the central-peripheral transitional region (TR) of the eighth nerve in elderly humans and to determine the reasons for its fragility, the eighth nerve root was studied by light and electron microscopy and by immunohistochemistry. Central and peripheral nervous tissue showed complex interdigitations at the TR. Slight proliferation of central glial tissue accompanied with disarranged course of the nerve fibers was also seen in this region. These findings were though to be age-related changes of the eight nerve. The capillaries ran in various directions at the TR and formed anastomoses with capillaries in the peripheral portion of the nerve. The density of capillaries in the peripheral nervous tissue was twice as high as that in the central nervous tissue. These findings indicated that the capillaries at the TR provide a connection between the blood supply to the central and peripheral portions of the eighth nerve. The occurrence of the age-related changes and complex course of the capillaries at the eighth nerve TR appeared to be related with the fragility of this region. PMID- 7993234 TI - The retention phase of treatment; the importance of root positioning as an aid to stability of the occlusion. PMID- 7993236 TI - The molar extraction debate. AB - Recent reports of conflict between dentists and orthodontists over the extraction of second molar teeth prior to orthodontic treatment raise a number of questions; one of which is: not whether or not to extract, but which teeth to extract. So that this controversial topic may be debated further, the Editor of this Journal has sought contributions from several quarters. Dr Harry Orton of the United Kingdom has written and lectured widely on this subject and recently lectured to the Western Australian Branch of the Australian Society of Orthodontists; his lecture has been summarised by Dr John Stamatis who has also compiled a review of the literature on the subject. Both the summary and the review are printed below together with some clinical experiences of the Editor. PMID- 7993235 TI - 14th Congress of the Australian Society of Orthodontists: lecture summaries. PMID- 7993237 TI - Computers and the orthodontist. PMID- 7993238 TI - The graphical analysis of tooth width discrepancy. AB - The standard tooth width ratio tables currently do not provide an overall indication of the final interdigitation of teeth. To provide a comprehensive analysis of inter-arch tooth width discrepancy, this study has developed a combination of cumulative percentage tooth width ratios and a method to visually determine the harmony between maxillary and mandibular tooth widths. Mesiodistal tooth widths from the first permanent molar to the corresponding first permanent molar were measured from 60 sets of pretreatment study models which were selected consecutively. Cumulative percentage ratios relating mandibular teeth to maxillary teeth were calculated utilising the mesiodistal tooth width measurements. The 13 mean cumulative percentage ratios developed in this study were plotted on graph paper showing plus and minus two standard deviations from the mean. These ratios provide a standard from which cumulative percentage ratios obtained from any new case may be compared graphically. Deviations from the mean cumulative percentage ratios are immediately recognised. No simple graphical method of assessment on the final interdigitation of anterior and posterior teeth has previously been devised. The graphical analysis of tooth width discrepancy is invaluable as an aid in localising any tooth width discrepancy and ensuring that incompatible maxillary-to-mandibular tooth widths are recognised prior to orthodontic treatment. PMID- 7993239 TI - Localisation of the unerupted maxillary canine: additional observations. AB - Occlusal radiographs are recommended for the tube shift method used to localise the unerupted maxillary canine. Several case histories are presented to explore how diagnostic occlusal films may be obtained. The initial maxillary incisor inclination determines the vertical angulation of the tube, while the mesio distal position of the canine crown determines the horizontal angulation of the tube to the mid-sagittal plane. Increased distances aid localisation: both the distance between the impacted tooth and its reference tooth, and the distance between the positions of the tube at exposure are significant. If an orthopantomogram and an occlusal film are to be taken as initial radiographs, the orthopantomogram should be read first to determine the position of the tube for the occlusal film. Radiographs taken previously may provide information on centring the tube for the occlusal film. The horizontal tube shift between two occlusal films is a more sensitive means of localising canines than is the vertical tube shift available between an orthopantomogram and an occlusal film. PMID- 7993240 TI - Tooth movement following third molar removal. AB - The mandibular dental arches of 45 young adults (mean age = 24.3 years) were analyzed by measuring study casts taken immediately before and twelve weeks after the removal of impacted third molar teeth. Arch length and width were measured at predetermined points on the study casts. The results showed significant buccal movement of mandibular second molar teeth following surgery (p < 0.01). Bilateral mesioangular impactions were associated with larger increases in mandibular arch width following surgery than unilateral mesioangular impactions or other classes of impaction (p < 0.05). The greatest amount of tooth movement was observed in cases where mandibular second molars had a pre-operative lingual inclination. It is hypothesised that mesioangularly impacted mandibular third molars can produce sufficient force to displace the adjacent second molar teeth in a lingual direction and when the adjacent third molar is removed this movement is reversed by functional forces. PMID- 7993241 TI - Ceramic bracket debonding: the evaluation of two debonding techniques and their effect on enamel. AB - Enamel fractures have been associated with the debonding of some ceramic brackets which have a chemical bond to the enamel. The purpose of this study was to assess the enamel surface subsequent to debonding Transcend series 2000 ceramic brackets using two debonding techniques. One hundred extracted human premolars were divided randomly into groups of two and prepared for bonding. Group 1 teeth had brackets bonded with Transbond light-cured adhesive and Group 2 teeth had brackets bonded with Unite chemically-cured adhesive. Bonded teeth were stored in normal saline at 37 degrees C for 5 days and thermocycled. Teeth in both groups were subdivided randomly into Subgroups A and B. Teeth in Subgroup A had brackets debonded with the Transcend debonding instrument while teeth in Subgroup B had brackets debonded with ligature cutters. Each tooth was examined under light microscopy and those teeth suspected of enamel fracture were assessed by scanning electron microscopy. Three out of the 100 teeth exhibited enamel fracture. There was no difference between the adhesive used and the number of enamel fractures or between the debonding technique used and the number of enamel fractures. A high proportion of brackets debonded with ligature cutters exhibited tie wing fracture. PMID- 7993242 TI - The role of CT, MRI and 3D imaging in the diagnosis of temporomandibular joint and other orofacial disorders in children. AB - Advances in medical imaging techniques add a new third dimension (3D computer reconstruction of CT, MR and Ultrasound images) to the diagnostic armamentarium of practitioners in orofacial medicine, surgery and Orthodontics. In particular, Computerized Tomography and Magnetic Resonance Imaging with, to a lesser extent, Nuclear Medicine Imaging and Sonography provide more accurate and detailed information on abnormalities and disorders of craniofacial osseous and soft tissues, especially the temporomandibular joint, than was previously available from plain films or tomography. Greater familiarity with these new imaging modalities by dental specialists will result in their more effective use in paediatric patients. PMID- 7993243 TI - Treatment planning by appliance selection. AB - Today, there is a wide variety of orthodontic appliances, each of which has its own particular advantages and disadvantages. Some of these appliances move teeth; others move elements of the skeleton, modify growth of hard tissues or modify functions of soft tissues. The modern orthodontist should select the appropriate "blend" of appliances in order to treat the individual problem, rather than follow a particular technique. This article discusses the merits of the various bracket systems that are available and explores how they may be combined to produce an individual appliance for each patient. PMID- 7993244 TI - A review of magnetic resonance imaging in spinal trauma. AB - One hundred and ninety-five magnetic resonance (MR) images (1.5 Tesla) of 167 patients with neurological impairment following spinal trauma were reviewed. Acute cord injury produces central haemorrhagic necrosis that extends transversely and longitudinally with time and increased injury severity. Oedoma is more homogeneous, extensive and dominant in minimal lesions. Magnetic resonance appearances correlate with neurological status and outcome. Patients with MR evidence of cord blood had severe clinical lesions and failed to show useful clinical improvement. Patients with homogeneous 'oedema' improved to useful function. Lesion signal inhomogeneity relates to a worse prognosis. The clinical level correlates closely with cord blood or signal in homogeneity but imprecisely with homogeneous oedema. Disc herniations require differentiation from epidural blood and venous engorgement, which are prominent with bone displacement. Magnetic resonance is recommended in incomplete cord syndromes and in cord injuries with no apparent fracture, particularly if clinically deteriorating. Chronic injury consists of cavitation, extensive gliosis, cord atrophy and leptomeningeal fibrosis. Progressive myelopathy may result from cystic or non-cystic intramedullary lesions. Cord cysts are common and cyst fluid signal should closely follow cerebrospinal fluid. Turbulent cyst fluid motion is commoner in larger cysts and may predict those cysts more prone to propagate. Progressive syrinxes show typical appearances, usually with transverse septa. Atrophy and propagating syrinxes usually take years to develop. Leptomeningeal cysts and spinal stenosis caused by bone displacement and accelerated adjacent disc disease may cause late deterioration. In progressive myelopathy following injury, surgically drainable cysts are clearly differentiable from cord gliosis and atrophy. PMID- 7993245 TI - Biliary dilatation in asymptomatic AIDS patients. AB - Cytomegalovirus (CMV) is a recognized cause of biliary abnormalities in acquired immune deficiency syndrome (AIDS) patients. In a prospective trial, two of 25 (8%) of AIDS patients on treatment for CMV related infections without biliary symptoms were found to have biliary dilatation on ultrasound. The study confirms previous findings of the poor correlation of sonographic findings with clinical status and biochemical profiles, and demonstrates that biliary tree dilatation in this group of patients may not per se warrant further invasive investigation. PMID- 7993246 TI - Bronchial artery embolization to control haemoptysis. AB - This is a retrospective study of 15 patients who had bronchial artery angiography and embolization for life-threatening haemoptysis in the period January 1986 to March 1993. Eight were male and seven were female, in the age range 32-77 years. Massive haemoptysis has a 50-100% mortality if treated conservatively and surgery has an up to 35% mortality in this high-risk group. Nine patients had advanced tumours. Seven had technically successful procedures, with haemoptysis being controlled in six and one patient dying from post-procedural massive haemoptysis. One of the patients with failed embolization died from massive haemoptysis and the other had spontaneous settling of bleeding. The other six patients suffered from bronchiectasis (2), aspergilloma involving tuberculous cavity (2), active tuberculosis (1), and abscess cavity presumably due to vasculitis (1). Technically successful embolizations were achieved in all six; three had control of haemoptysis, one required successful re-embolization after massive bleeding following initial embolization, one suffered continuing non-massive bleeding and one died soon afterwards from massive haemoptysis. PMID- 7993247 TI - Diverticular disease of the vermiform appendix and its clinical relevance. AB - The case of a solitary diverticulum of the appendix found on routine barium enema is presented. The types of diverticula, their presentations and their potential outcomes and significance are discussed. PMID- 7993248 TI - Carcinoma of the breast with sarcomatous metaplasia. AB - Carcinoma of the breast with sarcomatous metaplasia (CSM) is a rare and interesting tumour with a poorer prognosis than the usual breast malignancies. The mammographic appearances of this lesion have only previously been described once in the literature. A case of CSM is presented with mammographic-pathological correlation and review of the literature. PMID- 7993249 TI - Shoulder impingement syndrome: diagnostic accuracy of magnetic resonance imaging and radiographic signs. AB - Shoulder impingement syndrome is commonly encountered in orthopaedics. In a blinded retrospective study, magnetic resonance imaging and roentgenographic signs in 41 patients with clinical signs of impingement syndrome were compared with 40 control patients. Statistically significant differences between the groups included the absence of subarcromial fat, as well as the presence of a supraspinatus tear, subacromial osteophytes, and a decreased coracohumeral distance. Other signs reported to occur in patients with impingement syndrome did not vary significantly in the population studied. PMID- 7993250 TI - Segmental trends in cancellous bone structure in the thoracolumbar spine: histological and radiological comparisons. AB - Segmental variations in vertebral body cancellous bone architecture throughout the thoracolumbar spine were examined using histomorphometry and microradiography, and compared to bone mass measured using dual energy X-ray absorptiometry. In six human vertebral columns (T1 to L5) bone mineral content (BMC) and bone mineral density (BMD) of each vertebral body was determined in the lateral projection. Sagittal plane cancellous bone architecture was assessed from two-dimensional surface stained images and microradiographs of two 1 mm thick sections at each vertebral level. Computer-assisted image analysis was used to measure the total bone area (TBA), mean trabecular width (MTW) and trabecular number (TbN) from the stained images, and the skeletonized network length (SNL) from the radiographic images. Consistent segmental trends were observed for all structural parameters across the six columns examined. Higher TBA and TbN values were observed in the upper thoracic segments and decreased caudally. The MTW was relatively constant in the thoracic vertebrae before increasing in the lumbar spine. Pooled correlations between TBA and the bone density measurements were poor (BMC: r = 0.17, BMD: r = 0.25), while the TBA and SNL were only moderately correlated (r = 0.42). In conclusion, histomorphometric and radiological measurements appear to provide different information about cancellous bone structure. Bone structure is poorly correlated to integral measurements of bone mass. The consistent segmental variations in bone architecture appear to reflect a skeletal response to the relative extent of habitually applied loads in different regions of the spine. PMID- 7993251 TI - Imaging of the absent cervical pedicle syndrome. AB - Three cases of congenital absence of a cervical spine pedicle are described. This anomaly comprises a radiological triad of (i) the absent pedicle producing an apparently 'giant' neural foramen; (ii) a dorsally displaced ipsilateral articular mass and lamina with a dysplastic and reversed facet joint; and (iii) deficiency or absence of the ipsilateral transverse process. Recognition of this anomaly is particularly important in the context of acute injury to avoid misdiagnosis as a traumatic facet joint fracture-dislocation. The giant foramen must also be differentiated from expansion due to a neurofibroma. A correct plain radiographic diagnosis is usually possible, but in doubtful cases appearances on computed tomography are pathognomonic. Magnetic resonance imaging, performed in two of the cases, was helpful in elucidating the contents of the giant foramen, but should rarely be necessary in clinical practice. PMID- 7993252 TI - Sonography of abdomino-scrotal hydrocele. PMID- 7993253 TI - Evaluation of the healing process in fractures using early and delayed bone scanning. AB - Fifty-two fracture sites were evaluated by bone scintigraphy after acquiring similar views of the lesions at 4 and 24 h following technetium-99m methylene diphosphonate administration. After calculating 24/4 h radio-uptake ratio (RUR) and using 1.15 as the critical point of separation, fresh healing lesions could be separated from old healed fractures persisting as 'hot spots' with a sensitivity of 100% and specificity of 82%. The 24/4 h RUR technique is a new approach in measuring the osteoblastic activity at the lesion site. The technique appears to have clinical significance in the detection and follow up of the healing status of occult fractures where radiological procedures are of limited value. PMID- 7993254 TI - Allergic bronchopulmonary aspergillosis: a comparative evaluation of computed tomography with plain chest radiography. AB - Computed tomography (CT) was done in 15 consecutive patients with allergic bronchopulmonary aspergillosis (ABPA). When compared with chest X-ray, CT was found to be superior in the diagnosis of bronchiectasis in patients with ABPA. Of the 90 lobes studied, CT detected bronchiectasis in 57 lobes and plain chest X ray in 44 lobes. In addition to central bronchiectasis, peripheral bronchiectasis was diagnosed with CT in 18 of the 57 lobes. Follow-up CT was done in two patients after treatment for detection of progression or regression of bronchiectatic lesions. One patient showed radiological as well as clinical improvement, while the other patient presented with a recurrence of symptoms 4 months after stopping treatment. Computed tomography showed radiological progression of bronchiectasis and the patient was successfully treated with corticosteroids (thus preventing further bronchial damage). It is concluded from this study that CT is superior to plain chest X-ray in the diagnosis of bronchiectasis in patients with ABPA. Being non-invasive, it is also helpful in monitoring the course of bronchiectasis in these patients. PMID- 7993255 TI - Loss of the mucosal lining/gall-bladder wall echo: a sonographic sign of gangrenous cholecystitis. AB - An additional sonographic sign of gangrenous cholecystitis, namely the loss of the mucosal/gall-bladder wall echo in a setting of acute cholecystitis, is described. It was found prospectively in six patients and correlated well with the presence of mucosal/wall necrosis on histological gallbladder specimens. Other reported signs of gangrenous cholecystitis are reviewed. PMID- 7993256 TI - Computed tomography in acute small bowel obstruction. AB - The abdominal computed tomograms of 28 patients with a clinical diagnosis of acute small bowel obstruction were reviewed. Computed tomography accurately identified the presence, severity and level of obstruction. Signs such as angulated bowel loops and adjacent streaks within the mesentery at points of luminal calibre change were recognized in 69% of cases with adhesive obstruction. Computed tomography may reveal non-adhesive causes and is the modality of choice for investigating patients with higher grades of bowel obstruction where early surgical intervention is contemplated. PMID- 7993257 TI - Radiotherapy planning for lung cancer: can we do better? AB - Modern radiotherapy planning and treatment techniques allow the delivery of treatment with considerable geographic and dosimetric precision. Uncertainties and variability in the radiotherapy process prior to this stage, that is, localization of the target volume, has received little systematic study. The results of a planning study in non-small cell carcinoma of the lung are presented to highlight the possible variability in the planning process, both at an inter clinician and intra-clinician level. The implications of this survey, both in terms of treatment outcome and training issues, are discussed. PMID- 7993258 TI - Radiotherapy alone for early stage Hodgkin's disease: a 16 year experience at the Royal Adelaide hospital. AB - The records of all patients with stage I and II Hodgkin's disease treated with radiotherapy alone at the Royal Adelaide Hospital between 1970 and 1986 were reviewed. The aim was to ensure the results were equivalent to the best reported series, particularly as treating such patients with chemotherapy alone has been shown to produce equivalent overall survival figures with improved relapse-free survival. There were 104 patients of whom 67 had undergone staging laparotomy. Fifty-seven patients were stage I and 47 stage II. Nine patients had B symptoms. Overall survival at 10 years was 83% with disease-specific survival being 86% and relapse-free survival 68%. These results compare favourably with those in the world literature. Multivariate analysis only revealed stage as an independent predictor of improved relapse-free survival. The use of radiotherapy for most patients with early stage Hodgkin's disease is continued at Royal Adelaide Hospital. However, careful selection criteria need to be applied to minimize the incidence of relapse after radiotherapy. PMID- 7993259 TI - Leaking mycotic abdominal aortic aneurysm. AB - A case of leaking mycotic abdominal aortic aneurysm is reported, with a brief review of the literature. A 58 year old female presented with shoulder and abdominal pain associated with diarrhoea, vomiting and fever with leucocytosis. Computed tomography of the abdomen showed pooling of contrast in the retroperitoneum anterior to a non-dilated abdominal aorta. There was considerable retroperitoneal blood accumulating in a mass-like lesion in the right lower abdomen and pelvis obstructing the right renal collecting system. Laparotomy revealed a 4 cm diameter saccular aneurysm of the abdominal aorta, with a 1 cm diameter neck. Culture of the thrombus grew Streptococcus pyogenes. PMID- 7993260 TI - Unifocal Langerhans' cell histiocytosis (eosinophilic granuloma) resembling Ewing's sarcoma. AB - In a 9 year old boy, a destructive lesion in the diaphysis of the right femur was wrongly diagnosed as a Ewing's sarcoma on the basis of the radiologic findings and fine needle aspiration cytology report. The clinical and radiologic picture was suggestive of Ewing's sarcoma, but an open biopsy of the lesion revealed a histopathological pathological picture of eosinophilic granuloma. A brief review of the literature is given, together with discussion on the differential diagnosis of a mid shaft femoral lesion in young patients. PMID- 7993261 TI - Radiotherapy and concurrent chemotherapy for oesophageal carcinoma. AB - This retrospective non-randomized study reports the outcome of 67 patients who received radical radiotherapy with or without two courses of concomitant chemotherapy using 5-fluorouracil and cis-platin at Westmead Hospital from 1985 to 1992. The overall median survival was 14.0 months, the actuarial 5-year survival was 18%, and median disease-free survival was 11.3 months. Forty-eight per cent of the 67 patients had complete endoscopic response and this resulted in a significantly improved survival for those patients. A pretreatment baseline Karnofsky performance > or = 80, and a baseline swallowing score > or = 80 also predicted for better survival. The development of acute toxicity did not predict the likelihood of developing chronic toxicity. The incidence of stricture formation (benign and malignant) requiring dilatation was 37%. There was no significant improvement in overall or disease-free survival, nor significant worsening of toxicity in the group of patients who received concurrent radiotherapy and chemotherapy compared with patients receiving radiotherapy alone. PMID- 7993262 TI - Colour duplex ultrasound: a screening modality for femoropopliteal disease in patients with intermittent claudication. AB - In patients presenting with intermittent claudication, Colour Duplex Ultrasound (CDU) examination of the femoro-popliteal segment has been proposed as a screening modality. Those patients with atheromatous lesions suitable for percutaneous transluminal angioplasty (PTA) could proceed to diagnostic angiography. Patients with long segment occlusive disease demonstrated by CDU, who were not considered suitable candidates for surgery, would not require angiographic examination. This prospective study was performed on 46 limbs in 25 consecutive patients who presented for investigation of claudication. There was close correlation between the two methods in the demonstration of high-grade stenoses and occluded segments. Using angiography as the 'gold standard' this study indicated a diagnostic accuracy for CDU of 93% with a sensitivity of 89% and a specificity of 95%. Angiography tended to show longer occluded segments than CDU. Colour Duplex Ultrasound shows promise as a screening investigation in patients with intermittent claudication to detect lesions that may be suitable for PTA. PMID- 7993264 TI - After-hours radiology. AB - After-hours radiological procedures are essential but expensive in any major teaching hospital. Using the criteria that radiological procedures performed after-hours should have a reasonable probability of influencing or changing patient management acutely, a study of the justification of after-hours radiological procedures was performed at the Princess Alexandra Hospital. Computer print-outs were used to select the patients based on the dates and times of the procedures. Their charts were then reviewed. The study found that most after-hours radiological procedures were justified. However, it also identified certain procedures that need not be performed or at least could be reduced after hours. The procedures were: (i) computed tomography (CT) head--epilepsy, meningitis; (ii) CT abdomen--trauma (intubated)--unable to examine abdomen; (iii) CT spine--obvious unstable fractures; (iv) Ultrasound abdomen--biliary colic (afebrile); and (v) Ultrasound kidneys--renal failure (afebrile). PMID- 7993263 TI - Mammographic features of adenoid cystic carcinoma. AB - Adenoid cystic carcinoma of the breast accounts for < 1% of breast malignancies. This case report describes the mammographic features and the pathology. Adenoid cystic carcinoma is a well-circumscribed carcinoma that has a relatively good prognosis. PMID- 7993266 TI - Longitudinal stress fracture in the femoral diaphysis. AB - Stress fractures occur in multiple sites but more so in the lower limbs and show a predilection for certain sites. The lower femoral shaft is not a common site and a longitudinal stress fracture is extremely rare. A case is reported of a longitudinal stress fracture in the distal femoral shaft that was not suspected initially despite the patient's athletic activities. Review of the literature did not reveal documentation of any similar case. PMID- 7993265 TI - Distended iliopsoas bursa: case reports and anatomical dissection. AB - Distension of the iliopsoas bursa is usually seen in association with underlying hip joint disease. The computed tomography (CT) appearance is characteristic and allows a diagnosis to be readily made. Computed tomography will also facilitate needle placement for aspiration of bursa contents and the injection of water soluble contrast media for CT bursography. Three cases of iliopsoas bursa enlargement of varying underlying aetiology are presented. The dissection of seven cadavers demonstrated the anatomy of the normal bursa and highlighted its important role in the normal functioning of the iliopsoas muscle. PMID- 7993267 TI - Mucinous cystadenoma of the appendix with unusual sonographic appearances. AB - A case of an appendiceal cystadenoma resulting in a large mucocele in a 35 year old man presenting with abdominal pain is reported. On ultrasonography, an unusual appearance of strand-like layers of varying echo-texture suggesting a solid lesion was seen. On computed tomography, calcification and contrast enhancement of the rim was noted. The spectrum of imaging appearances of appendix mucoceles is reviewed. PMID- 7993268 TI - The utility of the Philips SRI-100 Real Time Portal Imaging Device in a case of postoperative irradiation for prevention of heterotopic bone formation following total hip replacement. AB - The new Radiation Oncology Department at the Heidelberg Repatriation Hospital in Melbourne, Australia commenced operation in June 1992. As part of quality control the Philips SL-15 linear accelerator was fitted with the Philips SRI-100 Real Time Portal Imaging Device (RTPID), the first such apparatus in Australia. One of its major advantages over older systems is its ability to provide a permanent hard copy of the image of the field treated. The computer image can be immediately manipulated and enhanced on the screen (with respect to such qualities as brightness and contrast) prior to the printing of the hard copy. This is a significant improvement over the more cumbersome older port films that required developing time, without any pre-assessment of the image quality. The utility of the Philips SRI-100 RTPID is demonstrated in the case of a patient irradiated soon after total hip replacement, as prophylaxis against heterotopic bone formation (HBF). The rapidity and quality of image production is a major advantage in these patients where post-operative pain may result in positional change between film exposure and image production. Extremely accurate shielding block position is essential to shield the prosthesis (and allow bone ingrowth for fixation) whilst avoiding inadvertent shielding of the areas at risk for HBF. A review of the literature is provided. PMID- 7993269 TI - Primary hyperoxaluria type I. PMID- 7993270 TI - The significance of hypoechoic renal rims. PMID- 7993271 TI - Youth suicide: a public health problem? PMID- 7993272 TI - Developing a code of ethics for psychiatry: the Australasian experience. AB - The first ever code of ethics of the Royal Australian and New Zealand College of Psychiatrists was promulgated in 1992. In this paper two of the four members of the College's Ethics Committee (which prepared the document) describe the code's provenance and the procedure used to determine its form and content. The code, a milestone in the College's history, reflects its maturity in confronting the many ethical issues with which psychiatrists have to wrestle in contemporary clinical (and research) practice. We hope that our account will assist them to deal effectively with this pivotal aspect of their professional work. PMID- 7993273 TI - Professional misconduct in psychiatry: sexual behaviour with patients. A report of recent New South Wales findings. AB - In the period 1989-1991 the Medical Tribunal in the state of New South Wales conducted enquiries into seven complaints about professional misconduct of a sexual nature incidental to psychiatric treatment. This study is submitted in the interests of patients, profession and public in accordance with the ethos of the Medical Practitioners Act (NSW). It is based on personal observations and published legal documents and refers to the legal context and procedures. It addresses the substance and style of complaints and complainants and of defences and respondents. The names of six psychiatrists and one trainee psychiatrist were removed from the Medical Register. In three instances decisions or orders were unsuccessfully appealed in the Supreme Court. In two instances associated complaints (of illicitly prescribing drugs of addiction and of divulging confidential information) were also found to be professional misconduct. Courtroom pitfalls are illustrated and practical principles explicit in judgements are reiterated. PMID- 7993274 TI - Alcoholism: development of the diagnostic concept. AB - This paper traces the diagnostic concepts of alcoholism featured in the major classification systems over the past 40 years. The description of alcoholism as a diagnostic concept has undergone considerable transformation over this time, but an international consensus now exists in the DSM-IIIR [2] criteria and ICD-10 [3]. Alcoholism is equated with alcohol dependence, and both definitions draw largely on the description of the alcohol dependence syndrome by Edwards and Gross [4]. Although the presence of withdrawal symptoms and relief use (key aspects of so-called physical addiction) is part of both systems, they are not necessary to make the diagnosis in either. Future directions and clinical implications of these developments are discussed. PMID- 7993275 TI - Clinical management of parasuicides: critical issues in the 1990s. AB - In view of recent rises in suicide rates of males aged 15-29 years, the literature on the specialised clinical management of parasuicides presenting at hospital is reviewed. Few studies demonstrate reduction in suicidal behaviour with such services, although substantial psychosocial benefits have been shown. These negative results with respect to suicidal behaviour partly relate to methodological problems such as small sample sizes, the exclusion of high risk subjects, short follow-up and confusing outcome measures. We cannot be confident that existing clinical practices have been effective in reducing suicide. Hence this paper focuses on selected issues of critical importance. Clinically, risk assessment is a problematic area worthy of clear understanding. There is a continuing confusion over the nature of affective disturbance associated with parasuicide and whether it might benefit from pharmacotherapy. Recent studies on the prevalence of psychological disorder in suicidal youth are discussed. Child abuse might usefully be screened for in parasuicidal patients, although this may be overlooked because of unfamiliarity with the association. New developments in cognitive and pharmacotherapies offer hope for suicidal rate reduction. There is a pressing need for further intervention studies. In particular, community and inpatient care of high risk patients require urgent evaluation. Further study of the role of depression and its appropriate management is needed. Although depression seems a significant factor, the recent rise in youth suicide remain largely unexplained. PMID- 7993276 TI - Psychotic speech: a neurolinguistic perspective. AB - The existence of an aphasia-like language disorder in psychotic speech has been the subject of much debate. This paper argues that a discrete language disorder could be an important cause of the disturbance seen in psychotic speech. A review is presented of classical clinical descriptions and experimental studies that have explored the similarities between psychotic language impairment and aphasic speech. The paper proposes neurolinguistic tasks which may be used in future studies to elicit subtle language impairments in psychotic speech. The usefulness of a neurolinguistic model for further research in the aetiology and treatment of psychosis is discussed. PMID- 7993277 TI - Differences according to recruitment method in subjects who care for a relative with schizophrenia. AB - With growing emphasis on community mental health care, there is increased research interest in the needs of people who care for a relative suffering from chronic mental illness. This methodological note examines the differences between two samples of caregivers for schizophrenia sufferers. The two samples were recruited by different methods from different sources: one a mail survey of a self-help group and the other through patients at psychiatric hospitals and outreach clinics. Differences were minimal and recruitment through self-help groups is advocated as the more cost effective method. PMID- 7993278 TI - Effectiveness of an assertive outreach community treatment program. AB - The purpose of this paper is to describe an Adult Community Treatment (ACT) program in Dandenong, Victoria, and its effect upon admission rates and time in hospital for 50 of the service's most disturbed patients. The implementation of the program was associated with a reduction in the annual re-admission rate from 38% (1989-90) to 21% (1990-91); the total length of hospital stay was also significantly reduced. The results support the value of community support programs in the management of the seriously mentally ill. PMID- 7993279 TI - Language, culture and psychiatric services: a survey of Victorian clinical staff. AB - In planning psychiatric services for non-English speaking immigrant communities it is essential to know what resources are available for the implementation of service plans. A survey of 991 professionals from a variety of disciplines working in Victorian state operated inpatient and community psychiatric services demonstrates that, although there is a substantial number of bilingual clinicians working in the system, there is a poor match between languages spoken by patient groups and clinicians, infrequent contact between bilingual clinicians and patients speaking the same language, and inadequate availability of interpreting services. Clinicians' knowledge of cultural issues relevant to assessment and treatment is inadequate, and there is some enthusiasm among clinical staff for remedying this deficiency. Clinicians express the opinions that services to non English speaking patients are inferior, and clinical outcome is worse than for the Australian-born. There appears to be general support for changes which would seek to more adequately meet the psychiatric service needs of immigrants. PMID- 7993280 TI - Police referrals to a psychiatric hospital: indicators for referral and psychiatric outcome. AB - Studies of police psychiatric referrals in the USA and the UK generally show these patients to be ill and in need of care. There are, however, no published Australian studies and such findings may not be validly generalised. This prospective study of consecutive police psychiatric referrals in Adelaide reports psychiatric assessment in 92 cases and observations by police in 69 of these, with no evidence of selection bias. The most common reason for referral was threat of self harm (28%). Mental illness was deemed to be present in 49% and the most common clinical description was "situational crisis" (29%). Schizophrenia was diagnosed in 18%. Clinicians viewed 19% of referrals as inappropriate. Increased relative odds for mental illness were associated with police accounts of psychotic symptoms, and decreased odds with threat of self harm and violence. Increased odds for admission were associated with language difficulties and damage to own property, decreased odds with threat to others, threat of suicide, and threat to self injury. There were 14 cases where possible charges were not being pursued: of these 7 were regarded as ill and 4 were regarded as inappropriate referrals. The rates of major disorders are lower than in other published work. It is proposed that this can be explained by relative ease of referral by police to psychiatry and flexible acceptance criteria. PMID- 7993282 TI - Depression and somatic symptoms: a cross-cultural study. AB - The study was carried out by the same research team in two metropolitan hospitals, one in Greece (N = 60) and one in Australia (N = 56). Subjects comprised patients consecutively admitted with a DSM-III-R diagnosis of depressive disorder, all of whom completed questionnaire measures of depression, anxiety and somatic symptoms. Clinical concepts and practices in the two hospitals were very similar. Overall levels of depression, anxiety and somatic symptoms in the two samples were almost identical, but there were differences in the pattern of somatic complaints: Greeks scored significantly higher on dizziness, paraesthesiae and masticatory spasms, and Australians scored significantly higher on drowsiness, hypersomnia and non-refreshing sleep, with the latter two items being the best discriminators of the two samples using discriminant function analysis. These findings, combined with factor analysis, suggested that symptoms associated with hyperventilation in the Greek sample, and with sleep disturbance in the Australian sample, explained most of the differences between them. PMID- 7993281 TI - Electroconvulsive therapy in a psychiatric intensive care unit. AB - This study reviewed all patients (N = 37) treated with ECT in a psychiatric intensive care unit during 1989-91. Diagnoses were: psychotic depression (8); bipolar disorder, manic phase (13); schizoaffective disorder (14); and schizophrenia (2). All patients were very severely disturbed and had failed to respond to medication given at highest levels judged to be safe, usually over 3-4 weeks. Response to ECT was generally rapid and marked, allowing substantial reductions in medication. To achieve the same clinical outcome for each course of ECT, 50% more unilateral than bilateral treatments were required, suggesting that bilateral ECT has a more rapid effect in this highly disturbed population. PMID- 7993283 TI - Patient satisfaction with a mood disorders unit: elements and components. AB - Patient satisfaction is an indicator of effective service provision and may influence compliance with treatment. Of 265 patients attending a specialised mood disorders unit and surveyed at least two years after their initial contact, 221 (83%) replied. Characteristics of responders and non-responders were compared on demographic and clinical information from index assessment and follow-up. Sixty four percent of responders were very satisfied and 21% partly satisfied with their management. Components of satisfaction included perceived competence of clinical management; the unit's administrative and after-treatment accessibility; and the support of staff and other patients. Those with a more adequate personality and melancholic depression at baseline assessment were more satisfied. A low current mood state at time of survey was associated with lower satisfaction in non-melancholics only. There were interactions between improvement in condition, diagnosis, personality and satisfaction. The survey provided a framework for formulating treatment programmes and was a useful quality assurance tool. PMID- 7993284 TI - The elderly admitted to a general hospital psychiatry ward. AB - In this retrospective study of 489 consecutive elderly admissions to a general hospital psychiatry ward, the main aim was to describe the stressors precipitating admission, psychiatric and medical diagnoses, physical treatments used, length of hospitalisation, and clinical and social outcome. Depression was the predominant diagnosis, with length of stay being correlated with depression severity. The main stressor associated with admissions was a change in medical status of the patient. At least two medical diagnoses were present in 70% of admissions, with many new physical illnesses being diagnosed. Significant improvement was found in 81% of admissions at discharge. Two thirds of admissions were discharged into independent living arrangements. While these outcomes suggested effective interventions, management difficulties were noted with the mix of elderly and young patients. It is recommended that acute psychogeriatric wards be developed in the general hospital and be located near geriatric medical wards. PMID- 7993285 TI - The association between spouse-reported Type A behaviour pattern and coronary heart disease. AB - This paper describes further validation of the Spouse-Report Type A Behaviour Pattern Questionnaire. In a case controlled study of 61 cardiac patients versus 61 community controls, the questionnaire was found to discriminate statistically between a group of patients with proven coronary heart disease and a group of matched healthy controls on the anger/hostility subscale and total Type A score. No relationship between Type A score and coronary heart disease severity was found. Possible explanations for these findings are examined. PMID- 7993286 TI - Psychiatric issues in the "loin pain and haematuria syndrome". AB - The Loin Pain and Haematuria Syndrome is a relatively new diagnosis applied to the problem of persistent loin pain, often with haematuria, in the absence of identifiable explanatory organic pathology. Case reports have suggested a range of salient psychopathological features associated with the complaints of pain and haematuria, although the psychological factors have been largely neglected in understanding the aetiology or in approaches to management. The roles of illness behaviour, patterns of somatisation, and psychiatric disorder associated with chronic pain syndromes, need to be addressed, as do the patterns of medical and surgical response to these patients. The use of the term "syndrome" to describe these symptoms implies a degree of uniformity in clinical features and outcome that has not yet been substantiated. New surgical techniques have been developed such as renal denervation and renal auto-transplantation to treat the pain, with limited success. A review of this condition illustrates the frequent failure of medicine to apply multi-factorial biopsychosocial models to understanding the aetiology and management of unexplained physical symptoms. It also illustrates the failure of our current nosology and understanding of somatoform disorders to achieve application outside psychiatry. PMID- 7993287 TI - The influence of spinal cord injury on coping styles and self-perceptions two years after the injury. AB - This study is a two year follow-up of previous longitudinal research which investigated the effects of spinal cord injury (SCI) on perceptions of control, self-esteem and coping styles over the first year of SCI. Persons with SCI and a demographically matched able-bodied control group completed standardised questionnaires on four occasions over two years. The instruments included the Locus of Control of Behaviour Scale (LCB), Rosenberg's Self-Esteem Scale, and an adapted Mental Adjustment to Cancer Scale (MAC), which measures coping styles, including fighting spirit, helplessness/hopelessness and fatalism. Results obtained in the first year were replicated in the two year data, except for the LCB Scale. After one year, the SCI group were found to perceive their life to be externally controlled, to be lower in self-esteem, and have more helpless/hopeless and fatalistic attitudes than the controls. There were no differences in self esteem and coping styles after two years for the SCI group. However, locus of control fluctuated over the two years, though there was a trend for the SCI group to be more externally focussed. There were no significant interactions between group and time. Implications for the adjustment of SCI persons are discussed. PMID- 7993288 TI - The clinical features of Tourette's disorder: an Australian study using a structured interview schedule. AB - The clinical features of an Australian series of patients fulfilling DSM-III-R criteria for Tourette's Syndrome (TS) were examined. Fifty patients, recruited from a hospital-based outpatient clinic and a self-help group, were interviewed using a structured schedule. TS is a complex disorder with wide ranging manifestations. Forty male and ten female TS patients with a mean age of 20.8 years (SD 11.2) were assessed. The mean age of onset of tics was 8.3 years (SD 3.3). Simple motor tics occurring in the rostral body regions were more common (eye 86%, face and head 80%) when compared both to simple tics occurring caudally (leg 52%) and complex motor tics (58%). Simple vocal tics were more common (94%) than complex ones (44%). There was a rostrocaudal pattern in the age of onset and severity of simple motor tics. Rates of comorbidity were 32%, 18% and 30% for Attention-Deficit Hyperactivity Disorder, Major Depression and Generalised Anxiety Disorder respectively and this was reflected in the considerable proportion (32%) of the sample who first presented for reasons other than their tics. There were substantial delays between the age of first presentation and diagnosis of TS owing to the insidious onset of the disorder, misdiagnosis and delays in presentation for help. A comparison of the features of the present patients with those of other published studies revealed similarities with some differences. Better clinical recognition of the symptoms and modes of presentation of TS may improve existing delays in diagnosis and treatment. PMID- 7993290 TI - Fluoxetine induced dyskinesia. AB - A case of fluoxetine induced dyskinesia in an elderly woman with previous use of low dose haloperidol is described. In contrast to neuroleptic induced tardive dyskinesia it was characterised by a rapid onset after commencing fluoxetine and rapid resolution on cessation. In the case discussion we describe other cases of fluoxetine induced extrapyramidal syndromes and possible mechanisms. PMID- 7993289 TI - Career choice and experience of distress amongst interns: a survey of New South Wales internship 1987-1990. AB - Successive cohorts of interns assigned to a Sydney teaching hospital since 1987 were interviewed at the beginning and end of their intern year to document factors influencing career choice and psychological morbidity, with comparisons between the graduates of the three NSW medical faculties. Intellectual challenge and altruism were the two most reported motivating factors in choosing Medicine. Many interns expressed regret at their career choice. Apart from anger, self reported psychological morbidity during internship was low. Interns' evaluation of the relevance of their undergraduate training declined during internship, except for Newcastle graduates. Increased "hands on" clinical experience during undergraduate years, career guidance, assertiveness training, and time management skills should be included in the undergraduate curriculum. More registrar teaching, frequent performance feedback, regular grievance sessions and decreased clerical activities contribute to more enriching intern experiences. PMID- 7993291 TI - Natural history of Khat psychosis. AB - A paranoid psychosis, resembling amphetamine psychosis, caused by chewing Khat (stems and leaves from the plant Catha edulis) has been well described. Our case demonstrates the natural history of Khat psychosis which, in previous case reports, has been vigorously treated with major tranquillisers. PMID- 7993293 TI - Self-inflicted enucleation of both eyes. AB - Categories of self-injurious behaviour are briefly reviewed. Serious and bizarre self injurious behaviour is usually psychotic in origin. The literature concerning self-inflicted enucleation of the eyes is reviewed and two additional patients, both with a diagnosis of schizophrenia, are reported. The lack of pain and the lack of concern shown by the patients and their management are discussed. PMID- 7993292 TI - Phenothiazine-associated supraventricular tachycardia. AB - Psychotropic medications, mainly phenothiazines, are known to be associated with cardiac insult. The case report presented here describes nearly fatal arrhythmia (sustained supraventricular tachycardia) consequent to phenothiazine treatment. The authors aim to alert psychiatrists to the possible adverse, and even fatal, effects of phenothiazines. PMID- 7993294 TI - Child maltreatment and later life psychopathology. PMID- 7993295 TI - Neglect of child psychiatry. PMID- 7993296 TI - Women in medicine. PMID- 7993297 TI - Clinical practice beyond science. PMID- 7993299 TI - Practice examinations. PMID- 7993298 TI - Clinical practice beyond science. PMID- 7993300 TI - The code of ethics and the law. PMID- 7993301 TI - Behavioral effects of persistent lymphocytic choriomeningitis virus infection in mice. AB - Lymphocytic choriomeningitis virus (LCMV) is a nonlytic murine virus that provides a valuable model system for studying the behavioral correlates of CNS viral infection. Newborn or immunosuppressed mice infected with LCMV develop a persistent tolerant infection characterized by continuous viral production. Virus can be found in various body organs including lung, liver, kidney, and brain. In brain, neurons are the predominant CNS cells infected and the greatest number of persistently infected neurons are found in the cerebral cortex, hippocampus, other limbic structures and parts of the hypothalamus. Despite continuous infection throughout the animal's life, neurons show no structural injury or dropout. Mice from the DBA/2J strain were infected with LCMV (1000 plaque-forming units) within 18 h of birth and tested for behavioral function as adults. Plaque assays indicated persistent infection in virus-injected mice. Mice were tested for their ability to learn a Y-maze spatial discrimination to avoid the onset of a mild footshock (0.43 mA). The number of correct avoidance responses made during training was taken as a measure of acquisition performance. The virus-infected mice showed a deficit in acquisition of the Y-maze discrimination compared to that seen in vehicle-injected and noninjected controls. Following additional training to reach control levels of performance, the infected mice and the controls were injected with the cholinergic antagonist scopolamine. Scopolamine (2.0 mg/kg) disrupted the performance of the infected mice significantly more than control performance, suggesting that a cholinergic dysfunction accounted for some of the learning deficit. A separate group of virus-infected mice exhibited hypoactivity during the first exposure to a locomotor testing apparatus.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7993302 TI - Lesions of supracallosal or infracallosal hippocampal pathways in the rat: behavioral, neurochemical, and histochemical effects. AB - Long-term behavioral and neurochemical effects of bilateral lesions to only the infracallosal component of the "so-called" septohippocampal pathways (cingular bundle, fimbria and fornix) have not been assessed. This experiment compared the behavioral, histochemical and neurochemical effects of supracallosal (SUPRA; cingular bundle) and infracallosal (INFRA; fimbria-fornix) hippocampal denervations in Long-Evans female rats. The rats were tested, over two periods (8 52 and 92-170 days postlesion), for open field locomotion, spontaneous alternation and radial-maze performance. Subsequently, histochemical or neurochemical determinations of cholinergic, serotonergic and noradrenergic hippocampal innervations were performed using acetylcholinesterase-staining, determination of high-affinity synaptosomal uptake of choline and serotonin, and measurement of hippocampal serotonin and noradrenaline concentrations by HPLC methods. Whatever behavioral test was considered, no significant effect was found in rats with SUPRA lesions, whereas rats with INFRA lesions were permanently impaired in all tests. Histochemical and neurochemical analyses showed hippocampal cholinergic as well as serotonergic markers to be substantially decreased in INFRA rats as compared to SHAM and SUPRA rats. The SUPRA rats exhibited a weak but significant reduction of both serotonergic and noradrenergic markers compared to SHAM and INFRA rats. These results suggest that lesions limited to the infracallosal pathway induce a hippocampal denervation sufficient to account for most of the behavioral, histochemical and neurochemical deficits classically reported following extensive lesions of the anterior hippocampal connections. Since the behavioral and neurochemical deficits were found to be lasting, it is suggested that bilateral infracallosal damage to the septohippocampal pathways might constitute an interesting paradigm of partial hippocampal deafferentation to investigate the effects of neural grafts or other treatments in an animal model of Alzheimer's disease. PMID- 7993303 TI - Delayed-response deficit induced by local injection of the alpha 2-adrenergic antagonist yohimbine into the dorsolateral prefrontal cortex in young adult monkeys. AB - Two young adult monkeys (Macaca mullata) were trained to perform a delayed response task that required the monkeys to remember a cued spatial position (left or right) over a delay interval and then to make a response to the cued position. Local injection of the alpha 2-adrenergic antagonist yohimbine (10 micrograms in 2 microliters saline) into the dorsolateral prefrontal cortex (Walker's area 46 and area 9) impaired the performance of the delayed-response task, and it was without effect on the performance of the task if there was no delay between the cue and choice signals. The main performing error after injection of yohimbine was that the monkeys responded to uncued position with higher rate. Local injection of the alpha 1-adrenergic antagonist prazosin (10 microgram in 2 microliters saline) or the beta-adrenergic antagonist propranolol (10 micrograms in 2 microliters saline) into the same cortical areas induced no significant effect on the performance of the task. The present study suggests that prefrontal alpha 2-adrenoceptors play an important role in the spatial working memory in young adult monkeys. PMID- 7993304 TI - Latent inhibition, overshadowing, and blocking of a conditioned antinociceptive response in spinalized rats. AB - Prior research has shown that a conditioned antinociceptive response can be established in spinalized rats by pairing stimulation to one hind leg (the conditioned stimulus, or CS) with tailshock (the unconditioned stimulus, or US). This suggests that spinal mechanisms can support classical conditioning. It is well known that in intact subjects, classical conditioning is undermined by preexposure to the CS (latent inhibition) or the concurrent presentation of either a more salient CS (overshadowing) or one that has already been associated with the US (blocking). In the present paper we show that these manipulations have a similar impact on the acquisition of a conditioned antinociceptive response in spinalized rats. These findings imply that similar principles may govern the acquisition of a conditioned response across different levels of the nervous system. PMID- 7993305 TI - Intrahippocampal administration of both the D- and the L-isomers of AP5 disrupt spontaneous alternation behavior and evoked potentials. AB - We previously reported that systemically administered N-methyl-D-aspartate (NMDA) antagonists significantly impair spontaneous alternation behavior. Others have reported that the restricted blockade of hippocampal NMDA receptors disrupts performance on different tests of spatial learning and have suggested that the resulting impairments are attributable to a disruption of endogenous NMDA dependent long-term potentiation (LTP). In the present study, we determined whether spontaneous alternation performance was disrupted by circumscribed blockade of hippocampal NMDA receptors as well as by a second class of compounds which disrupt LTP, protein kinase inhibitors. The effect of hippocampal NMDA blockade on inhibitory avoidance was also examined insofar as this behavior too is disrupted by systemically administered NMDA antagonists. When injected into the hippocampus 15 min prior to spontaneous alternation testing, the NMDA antagonists CPP and D,L-AP5 each decreased alternation rates. The specific protein kinase C (PKC) inhibitor, NPC 15437, also disrupted spontaneous alternation, whereas the more general kinase inhibitor, PMXB, did not. When injected 15 min prior to inhibitory avoidance training, CPP also impaired inhibitory avoidance learning as assessed during a subsequent test session, 48 h later. Interpretation of these data was complicated by the additional findings that intrahippocampal infusion of L-AP5 (which is inactive with respect to NMDA receptors) also disrupted alternation performance, and that both the D- and the L isomers of AP5 as well as each kinase inhibitor dramatically disrupted evoked responses (i.e., population spike amplitude, spike latency, and EPSP slope), as recorded in the dentate gyrus and evoked by perforant path stimulation. These data indicate that behaviorally effective doses of AP5 may have effects which extend beyond NMDA blockade. Moreover, the effects of these compounds on hippocampal transmission, in general, suggest that attribution of the amnestic consequences of their administration to impaired LTP may be unwarranted. PMID- 7993307 TI - Spine morphology of neurons in the avian forebrain is affected by rearing conditions. AB - An area of the caudal forebrain of male zebra finches, the Archi-Neostriatum caudale (ANC), which is active during arousal (Bischof & Herrmann, 1986, 1988), shows rearing-dependent changes in neuron morphology (Rollenhagen & Bischof, 1991). We demonstrate here that rearing conditions also affect the shape of spines of one of the four ANC neuron types. This neuron type was examined in birds reared under five different conditions--in isolation (1), caged (2), in the aviary (3), and with social contact (4) or chasing (5) after an isolation period. Our results show that social experience determines the proportion of the three types of spines (thin, mushroom, and stubby) of the investigated neuron type. Rearing conditions and short social contact also affect the spine stem length of the thin spine type. Long-term isolation results in a reduction in number and elongation of shafts of thin spines, along with an increase of stubby-and mushroom-shaped spines. Short-term social contact or arousal enhances the number of mushroom-and thin-shaped spines and reduces the length of spine stems of thin spines. We suggest that isolation prevents the ANC neuron from reaching full development. The increase of mushroom and thin spine types due to social contact indicates that the stubby-shaped spines are replaced by, or transformed into, mushroom-shaped spines, and the mushroom-shaped spines are replaced by, or transformed into, thin spines. These results confirm and extend the experimental background for our hypothesis (Rollenhagen & Bischof, 1991) that social contact is necessary for development of normal morphology of ANC neurons. PMID- 7993306 TI - Activation of adenosine A1 receptors in the nucleus accumbens impairs inhibitory avoidance memory. AB - Potent and highly selective adenosine A1 and A2 receptor agonists were bilaterally injected into the nucleus accumbens of mice 10 min prior to inhibitory avoidance training. Retention of the inhibitory avoidance response was assessed 24 h after training. Intra-ACB activation of A1 receptors, but not A2a receptor activation, significantly impaired the performance of mice during the subsequent retention test. Furthermore, the retention deficit produced by activation of A1 receptors was significantly attenuated by pretreating mice with a highly selective A1 receptor antagonist. These findings suggest that endogenous adenosine may modulate information processing in the ventral striatum via adenosine A1 receptors. PMID- 7993308 TI - Involvement of alpha- and beta-noradrenergic receptors in the effects of hippocampal vasopressinergic treatment on retrieval and relearning. AB - Biochemical investigations show that vasopressin interacts with noradrenalin to potentiate noradrenalin-induced accumulation of cyclic-AMP in the hippocampus, via the beta-adrenergic receptors. We previously showed in BALB/c mice that the effects of vasopressin (bilaterally injected at a 25-pg dose) in the ventral hippocampus were more effective than in the dorsal hippocampus on the retrieval and relearning of a Go-No Go visual discrimination task. Considering our results and those reported by biochemical investigations, we evaluated possible noradrenergic-vasopressinergic interaction in the ventral hippocampus under our behavioral conditions. To do so, we first explored the effects of propranolol and phentolamine, antagonists of beta- and alpha-adrenergic receptors, respectively. Second, we assessed the modifications in the vasopressin-induced improvement of retrieval and relearning by pretreating the subjects with either propranolol or phentolamine. Third, we tested the treatments in a locomotor activity task to determine whether the effects demonstrated in the two preceding experiments could be partially due to locomotor alterations by the drug. The results indicated that bilateral injection of propranolol (1 microgram on each side), which did not appear to affect the retention performance itself, completely blocked the enhancement of retrieval and relearning resulting from the vasopressin treatment. In contrast, bilateral injection of phentolamine (1 microgram on each side), which moderately improved retrieval, enhanced the vasopressin effect. The present results lend further support to the view that both noradrenalin and vasopressin play important roles in retrieval and relearning processes. More importantly, they provide additional support for the functional interaction of the noradrenergic and vasopressinergic hippocampal systems. PMID- 7993309 TI - Educational and occupational achievements of brothers and sisters in adoptive and biologically related families. AB - The study of brothers and sisters from adoptive and biologically related families permits unique analyses of the determinants of young adults' educational and occupational achievements. Brothers and sisters come from the same homes, neighborhoods, and usually schools. Many differences among families are controlled by the study of siblings. In addition, adoptive families influence their children only through the environment they provide, whereas biologically related parents transmit their intellectual and personal characteristics to their offspring genetically as well. Thus, the comparison of models of adult achievements for children from adoptive and biologically related families can inform us about the true effects of family environments, apart from genetic transmission (Scarr and Weinberg, 1978, 1980). In this follow-up study of 450 biologically related and adopted young adults (ages 22 to 30 years), we report on the family resemblances in educational and occupational achievements. Parents' reports were obtained on 97% of the original sample (N = 443), and 77% of the young adults participated in the follow-up study themselves; complete educational and occupational data were available on 303 young adults. Results show that biological sons are more influenced by their family backgrounds than daughters, regardless of genetic relatedness. A second finding is that young women's achievements are not as predictable from their own earlier achievements as are those of their brothers. A third finding is that parents invest in their sons' educational futures, regardless of sons' abilities and achievements, in ways they do not invest in their daughters' postsecondary educations. Sibling correlations and natural mother-adopted child correlations suggest that test scores, high school performance, postsecondary education, and even later occupational status can be influenced by genetic variability in personal characteristics that affect such achievements. PMID- 7993310 TI - Human parental behavior: evidence for genetic influence and potential implication for gene-culture transmission. AB - A large sample of adult twins (1117 pairs), who were concordant for having had children were asked to report on their child-rearing practices. A 14-item version of the Parental Bonding Instrument (PBI) was used to assess rearing practices of parent twins. The two factors of Care and Overprotection, commonly found in other studies, were recovered from this analysis of the PBI's parent form. Model fitting analyses indicate that human parental behavior is under significant genetic influence. Findings further suggest that this influence is sex limited, with a higher heritability in mothers than in fathers, and that it may result partly from the expression of dominant genes. For both PBI factors and both parents, the best-fitting models invariably assumed sex-limited genetic effects and unique environmental influences only. Broad heritability ranged from 19% (father overprotection) to 39% (mother care). These results are interpreted in the broader perspective of gene-culture theory. PMID- 7993312 TI - Biometrical genetic analysis of the cotwin control design. AB - The twin-cotwin matched case-control design can be interpreted in terms of bivariate genetic factor models. I derive expressions for the expected intrapair difference for a trait correlated with the variable on which discordance was selected. PMID- 7993311 TI - No differential heritability of intelligence test scores across ability levels in Norway. AB - The possibility of differential heritability of intelligence test scores across levels of ability has been raised in several recent reports. In the present paper intelligence test data from 862 monozygotic and 1325 dizygotic male twin pairs tested at about 19 years of age were analyzed in search for changes in heritability and shared environmentality as a function of ability level. The analyses were performed by means of multiple regression models (e.g., Cherny et al., 1992). No evidence of differential heritability across different ability levels was detected. PMID- 7993313 TI - Commingling and segregation analysis of reading performance in families of normal reading probands. AB - This paper reports the results of commingling and genetic segregation analyses performed on a quantitative reading phenotype in 125 families ascertained through normal, nondisabled readers. Commingling analysis using SKUMIX suggested that the reading phenotype best fit a skewed, single distribution model. Complex segregation using POINTER was then performed on the power adjusted data. While there were some analytical ambiguities and complexities, the segregation analysis indicated that there was familial transmission of the phenotype and that a significant percentage of the variance in this phenotype could be attributed to a major gene with dominance. Because the estimated frequency of the putative dominant allele is .35, 57% of the population would carry at least one copy of this allele. This common allele, with low penetrance, accounted for 54% of the phenotypic variance in reading scores. These findings are considered in the context of our earlier report of major gene influence ona qualitative dyslexic phenotype in a sample of 133 dyslexic proband families that were originally matched to the present sample of control families (Pennington et al., 1991). The applicability of a classic single gene, multifactorial-polygenic, and oligogenic or QTL models for reading ability/disability is discussed. PMID- 7993314 TI - Spouse similarity in attitudes, personality, and psychological well-being. AB - The study of the origin of spouse similarity is interesting because the extent to which spouse similarity reflects genetic resemblance between husbands and wives affects the genetic structure of a population. The sources of observed spouse similarity in attitudes, personality, and psychological well-being are discussed. Analyses based on data collected from an American adult sample assessed longitudinally showed that spouse correlations were high for attitudes and low to moderate for personality and psychological well-being. Four competing explanations to spouse similarity were compared: initial similarity, attrition, convergence, and age covariation. The results did not support the latter three explanations, indicating that initial similarity may be an appropriate interpretation of observed spouse similarity. The findings are consistent with those of other comparable studies. PMID- 7993315 TI - Continuity and change in infant shyness from 14 to 20 months. AB - Objective measures of shyness in the MacArthur Longitudinal Twin Study were obtained in two testing situations: the laboratory and the home. A longitudinal hierarchical model was fitted to the data, allowing estimation of the extent to which genetic, shared environmental, and unique environmental influences contributed to continuity and change of the shyness phenotype from 14 to 20 months of age. The sample consisted of 163 monozygotic and 138 same-sex dizygotic twin pairs. Models were fitted to raw data using a maximum-likelihood pedigree approach. Genetic, shared environmental, and unique environmental first-order factors, with specific variances, were modeled on each of four shyness ratings assessed in the laboratory and home at 14 and 20 months. Four second-order genetic, shared environmental, and unique environmental factors were also modeled. Results indicated that developmental change from 14 to 20 months and situational specificity between the laboratory and the home are mediated largely by shared and unique environmental influences. Genetic variation is largely responsible for both the stability in shyness from 14 to 20 months and the phenotypic correlations observed between the laboratory and the home settings. PMID- 7993316 TI - The inactive mutation leads to abnormal experience-dependent courtship modification in male Drosophila melanogaster. AB - Flies carrying the inactive mutation of Drosophila melanogaster have only 15% wild-type titers of the putative neurotransmitter octopamine. With a view to discovering whether the inactive mutation impairs learning, I describe the effect of the inactive mutation on experience-dependent courtship modification (EDCM). Wild-type males rapidly condition to immature males and modify their behaviour toward subsequent target flies. The weaker EDCM phenotype of inactive males is similar to that of dunce males. Using time-sampling, habituation is most rapid for wild-type males and slowest for dunce males, with inactive males showing an intermediate phenotype. These results support the notion that octopamine plays a significant role in the manifestation of Drosophila learning behavior. PMID- 7993317 TI - Tsukuba high- and low-emotional strains of rats (Rattus norvegicus): an overview. AB - This report compiles the results of a series of studies on the Tsukuba High- and Low-Emotional strains (THE and TLE) of rats (Rattus norvegicus) established at the University of Tsukuba, Japan. The THE and TLE strains have been selected, respectively, for low and high activity in a runway test. During the course of selection, defecation has increased in the THE strain and decreased in the TLE strain. These strain differences were not affected by maternal influences, early experience, or psychotropic drugs. THE rats were consistently inactive in all novel situations examined, while TLEs were very active. The level of spontaneous activity, however, was similar between the two strains. It was remarkable that THE rats showed more burrowing activity than TLE animals, whereas the latter displayed more aggression than the former. Differences in learning ability, concentration of neural transmitters, and social behavior were examined. PMID- 7993318 TI - Evaluating activity and emotional reactivity in a hexagonal tunnel maze: correlational and factorial analysis from a study with the Roman/Verh rat lines. AB - Two hundred forty 30-day-old Roman high- and low-avoidance (RHA/Verh and RLA/Verh) rats (divided equally by line and gender) which had received several peri- and/or postnatal treatments, forming two factorial [line x sex x treatment(s)] experimental designs, were tested in a hexagonal tunnel maze including a brightly illuminated central arena. The present study reports the results of correlational and factorial (principal-components) analyses performed on the data from those two experimental constituencies. The purpose of the study was to evaluate the validity of the hexagonal tunnel maze for testing emotionality, and therefore, the following measures were included in the analysis: entries into the central illuminated arena, total activity during testing, defecation during testing, and defecation during handling and weighing after testing. An overall pattern of negative correlations (or opposite loadings in the principal-components analyses) between defecation (especially during maze testing) and entries into the illuminated center and activity was found, thus giving support to the validity of entries into the illuminated center as being indicative of emotional reactivity. PMID- 7993319 TI - Biometrical analysis of larval digging behavior in Drosophila melanogaster. AB - Digging behavior of D. melanogaster larvae increases as larval development proceeds. Diallel crosses were made to analyze genetically digging behavior at 72 and 108 h of larval age. Additive and dominance variation was found, dominance being principally to dig. Dominance to dig is higher at 108 than 72 h of development; additivity does not substantially change between these two larval ages. At 72 h of larval age, depending on the cross, I found (i) dominance to dig, (ii) dominance to nondig, (iii) overdominance to dig, and (iv) no dominance to dig. At 108 h of larval development I detected (i) dominance to dig and (ii) overdominance to dig. Thus, diversity of response in the F1 was greater at 72 than 108 h of larval development. These age-related changes in larval digging behavior of D. melanogaster seem to reflect epigenetic changes in the patterns of gene expressions. PMID- 7993320 TI - Genetics of a nonoptimal behavior: oviposition preference of Drosophila mauritiana for a toxic resource. AB - Among three sibling species of the D. melanogaster subgroup, two are generalists (D. simulans and D. mauritiana), while the third, D. sechellia, specializes on a single toxic resource, the fruit of Morinda citrifolia. D. sechellia, resistant to the toxics, prefers to oviposit on morinda; D. simulans, which is very sensitive, is strongly repelled. D. mauritiana exhibits an aberrant behavior since it prefers to lay its eggs on morinda, where its embryos are killed. Oviposition behavior, studied in parental species, F1 hybrids, and backcrosses, was mostly an additive genetical trait. Further investigations were made with D. mauritiana and D. simulans carrying recessive markers. The X and second chromosomes had no effect, while a clear effect was found for chromosome 3. Since the toxicity of morinda is due to middle-length fatty acids, the behavior of the three species toward various acids was investigated. We found that D. sechellia exhibited a general oviposition preference for acids, while D. simulans was repelled by acids with at least four carbons. Surprisingly D. mauritiana exhibited behavior quite similar to that of D. simulans. Preference for morinda in D. sechellia and D. mauritiana could be mediated by different chemicals. PMID- 7993321 TI - Locating human quantitative trait loci: guidelines for the selection of sibling pairs for genotyping. AB - Simulation studies were conducted to assess the relative merits of different nonrandom sampling strategies for the selection of sibling pairs for genotyping in the attempt to locate individual loci (QTLs) contributing to variation in human quantitative traits. For a constant amount of variation contributed by a QTL (25% of the total) the frequencies and dominance relationships of a trait increasing allele were varied. Three strategies for selection of pairs for genotyping were based on the phenotypic values of the siblings: "Concordant sib pairs" (CSP) are pairs in which both individuals exceed a given threshold value; "discordant sib pairs" (DSP) are pairs in which one member exceeds a given upper threshold and the other is below a specified lower threshold; and "most similar pairs" (MSP) are pairs selected for falling below a specified percentile ranking of the within-pair mean square for the quantitative trait. Tests for linkage with markers at 1, 2, 5, 10, and 20 cM from each of the QTLs were conducted for each of the selected samples and compared with tests based on the regression, in the entire sample, of within pair variation on the proportion of alleles identical by descent (IBD) at each marker locus. Tests for the effect of the increasing allele at the QTL ("candidate gene") were also conducted for the DSP pairs. No single nonrandom selection procedure yields as much as half the information realized in the total sample. However, a combined strategy which involves genotyping the 5% of MSP and DSP for the upper and lower quintiles of values of the quantitative trait (a further 3% of the sample approximately) yields lod scores which are usually more than 65% of the values realized for the entire sample. Tests comparing the proportion of increasing alleles in high- and low-scoring siblings from DSP samples are uniformly very powerful for detecting candidate loci. Even when it is not possible to measure the entire range of the phenotype with uniform precision, some attempt to differentiate among individuals in a common "unaffected" class of individuals can lead to considerable increase in power. PMID- 7993322 TI - A simple method for censored age-of-onset data subject to recall bias: mothers' reports of age of puberty in male twins. AB - Genetic analysis of variation in age of onset of development milestones or psychopathological behaviors has been little researched, owing largely to the computational difficulty of dealing with "censored" observations. Censored observations arise when the only information on individuals is that they have reached a particular age but without onset having occurred. This paper shows how models can be simply fitted to such data using programs that can perform genetic analysis of categorical data by maximum likelihood. The method is illustrated using the program Mx with data on maternal report of the onset of puberty in twin sons from the Virginia Twin Study of Adolescent Behavioral Development. Frequently, data on age of onset is collected by retrospective recall. This can pose a variety of measurement problems. Suggestions are made for models that account for some of these problems or are robust to their presence. Substantial evidence for "telescoping" of onset dates is found for the puberty data. If left unaccounted for, these effects can artifactually inflate estimates of common environment effects. PMID- 7993324 TI - Prevention of depressive symptoms in school children. AB - This paper describes the development and preliminary efficacy of a program designed to prevent depressive symptoms in at-risk 10-13 year-olds, and relates the findings to the current understanding of childhood depression. The treatment targets depressive symptoms and related difficulties such as conduct problems, low academic achievement, low social competence, and poor peer relations, by proactively teaching cognitive techniques. Children were identified as 'at-risk' based on depressive symptoms and their reports of parental conflict. Sixty-nine children participated in treatment groups and were compared to 73 children in control groups. Depressive symptoms were significantly reduced and classroom behavior was significantly improved in the treatment group as compared to controls at post-test. Six-month follow-up showed continued reduction in depressive symptoms, as well as significantly fewer externalizing conduct problems, as compared to controls. The reduction in symptoms was most pronounced in the children who were most at risk. PMID- 7993323 TI - Type A personality in Australian twins. AB - We examined the genetic and environmental determinants of Type A behavior in 200 pairs of same-sex twins as measured by the structured interview (SI) of Rosenman and Friedman and by the Bortner questionnaire (BARS). As noted previously, these measures are poorly correlated (r = .30). Quite different heritabilities were found for the two measures (63% for SI, 23% for BARS), and the correlation between the two was found to be largely genetic. Although the sample size meant that differences in correlation between MZ and DZ twins on the BARS were not significant in univariate analyses, they were suggestive of twin competition effects, as other twin studies have found. We conclude that further genetic analyses should concentrate on component behaviors rather than the overall Type A construct. PMID- 7993325 TI - Acquisition of blood, injury, and needle fears and phobias. AB - The origins of fear and phobia of blood, injury, and injections were investigated in a sample of 128 fearful university students. Based on Mutilation Questionnaire scores, subjects were designated as common fear, high fear, or phobic. Ss reports of their onset experiences obtained from structured interviews were categorized into one or more acquisition pathways of conditioning, vicarious observation, and information. Of the 73% of Ss who recalled one or more onset experiences, 76% reported conditioning-like events as the primary pathway with the majority reporting fear-related UCSs. Vicarious experiences were reported as primary by 20% and 3% reported information as being primary in their fear onset. Severity of fear was unrelated to the pathway by which it was acquired, to whether the onset was recalled, and if recalled, whether it was due to a single or to multiple traumatic events. Results are discussed in terms of methodological problems of memory issues and means by which data are collected. PMID- 7993326 TI - Detection of somatic sensations in panic disorder. AB - Twenty-four panic disorder patients and 25 nonclinical subjects underwent double breath inhalations of 5, 10, and 20% carbon dioxide (CO2) or room air. All subjects were blind to inhalation content and were required to guess if the inhalation contained CO2. There was no significant difference between groups in the accuracy with which they were able to detect CO2 at any concentration. Similarly, the number of somatic symptoms reported to each inhalation did not differ between groups. The findings question suggestions that individuals with panic disorder are more accurate at detecting changes in physiology than other individuals. PMID- 7993327 TI - Personally relevant intrusions outside the laboratory: long-term suppression increases intrusion. AB - It has been suggested that the suppression of unwanted thoughts may increase their frequency and that this effect may contribute to some psychological problems. Previous studies have examined this over a period of minutes, in an artificial setting. Suppression over a four day period was evaluated in the present study. Each S was asked to identify a negative intrusive thought which he or she experienced and to record each occurrence of it in conditions designed to maximise the similarity to those experienced by obsessional patients. Ss were randomly allocated to one of three groups. One group was asked to suppress their thoughts whenever they occurred, another group was asked to think about their thoughts whenever they occurred and the third group just recorded the thoughts whenever they occurred. This design allowed experimental control of both attention to and manipulation of the target thoughts in contrast to attention and active suppression. It was found that Ss who suppressed their thoughts experienced more thoughts and found them more uncomfortable than Ss in the other two groups. This is consistent with the theory that suppression increases thought frequency and may be important in the development and maintenance of some disorders. PMID- 7993328 TI - Effects of priming and suppression of worry. AB - High and low worriers were primed by a short period of worry, suppression of worry, or the same period of non-worrying thought. Analysis of thoughts during the period following showed that worriers had more than twice as many unpleasant thoughts as did controls, across all prior conditions. Priming condition had little effect on this difference, although worry suppression was associated with a slight increase in the frequency of neutral or pleasant thoughts in high worriers, and a slight decrease in controls. These results are taken as evidence against the hypothesis that suppression of upsetting thoughts increases their intrusive quality, and thereby contributes to anxiety disorders. PMID- 7993329 TI - Worry and the suppression of imagery. AB - This experiment investigates Borkovec's theory that the function of worry is to protect people from potentially distressing emotional imagery. The experiment builds on a previous one of Borkovec and Inz (Behaviour Research and Therapy, 28, 153-158, 1990) comparing the frequency of thoughts and images in imagery and relaxation. The present experiment confirms the previous finding that worry is associated with less imagery than relaxation, but shows that this is not distinctive to worry. Indeed, an additional control condition, 'present-oriented mentation', was associated with even less imagery than worry. The fact that other kinds of thinking are at least as effective as worry in suppressing emotional imagery indicates that this property of worry is not sufficient to explain its occurrence. PMID- 7993330 TI - Behavior therapy for drug abuse: a controlled treatment outcome study. AB - 82 Ss were studied in a comparative evaluation of a behavioral vs supportive treatment for illegal drug use. Behavioral treatment included stimulus control, urge, control, contracting/family support and competing response procedures for an average of 19 sessions. 37% of Ss in the behavioral condition were drug-free at 2 months, 54% at 6 months, and 65% at 12 months vs 20 +/- 6% for the alternative treatment during all 12 months. The behavioral treatment was more effective across sex, age, educational level, marital status and type of drug (hard-drugs, cocaine, and marijuana). Greater improvement for this condition was also noted on measures of employment/school attendance, family relationships, depression, institutionalization and alcohol use. PMID- 7993331 TI - Qualitative dimensions of normal worry and normal obsessions: a comparative study. AB - Despite the crucial role typically given to negative thoughts in cognitive conceptualizations of emotional problems, few studies have compared the characteristics of varieties of such thoughts. The present study compared the process features of naturally occurring worries and obsessions in a non-patient group. Analyses of variance revealed several significant differences between these types of thought. The relationship between worries and obsessions, and the clinical and conceptual importance of the observed differences is briefly discussed. PMID- 7993332 TI - The Thought Control Questionnaire: a measure of individual differences in the control of unwanted thoughts. AB - Previous research has suggested that unpleasant and unwanted thoughts are a frequent experience in both normal and clinical populations. This paper describes the development and validation of a questionnaire that assesses strategies for controlling such thoughts. Analyses of the Thought Control Questionnaire (TCQ) demonstrated five replicable factors: Distraction; Social Control; Worry; Punishment and Reappraisal. Significant associations were found between the punishment and worry subscales of the TCQ and various measures of emotional vulnerability and perceptions of impaired control over cognition. The implications of these findings are discussed in relation to the literature on thought suppression, worry and mental self-regulation. PMID- 7993333 TI - The utility of the PND statistic: a reply to Allison and Gorman. AB - Quantitative synthesis ("meta-analysis") of single-subject research has rarely been conducted, partly because of a lack of agreement on how study outcomes are to be quantified. This article provides a response to Allison and Gorman (Behaviour Research and Therapy, 31, 621-631, 1993), who listed some problematic characteristics of use of the PND (percent of non-overlapping data) statistic for computing single-subject study outcomes, and recommended a regression-based solution to computation of effect sizes from single-subject research reports. Although Allison and Gorman are generally accurate in pointing out some limitations of the use of the PND statistic, they have been less thorough in identifying its relative strengths. Among these strengths is the fact that the PND statistic and its variations (a) have been shown to be strongly related to qualitative, "expert" ratings, (b) have been successfully employed in at least seven separate integrative reviews, and (c) have produced results which are complementary to more qualitative reviews of the same literature. In contrast, Allison and Gorman did not report results of applications of their procedure and, although their procedure has apparent theoretical support, it may be less useful in synthesizing existing single-subject literature. PMID- 7993334 TI - [Claude Bernard (1813-1878)--remarks on his methodology]. AB - Claude Bernard is the most distinguished French physiologist of the 19th century. He has not only performed a great number of scientific experiments. Moreover he has formulated a strictly reasoned methodology. It seems to be very useful to observe it even in temporary scientific work. Unprejudiced observations and experiments initially carried out only in thoughts are necessary premises for the formation of well supported working hypotheses. Only under these prerequisites practical experiments are justified as a decisive control. Claude Bernard emphasizes the idea that in spite of the rational principles of research the scientist is not immune to psychological dangers leading him to erroneous concepts as dogmatization of scientific statements, uncritical assumption of scientific fashions and last not least undue respect for personal authorities. The applicability of Claude Bernard's methodology is scrutinized and interpreted by three examples of the fate of scientific problems. PMID- 7993335 TI - [The detection of salmonellas using Rambach agar]. AB - Selective enrichment in Rappaport-Vassiliadis medium of 1595 animal fed samples and of 82 feedstuff and carcass meal was streaked simultaneously onto water-blue metachrome-yellow-lactose-agar acc. to Gassner, onto brilliant-green-phenol-red lactose-agar acc. to Kauffmann and onto Rambach agar. Salmonellae were isolated in 34 cases with Rambach agar (sensitivity 94.4%), in 33 cases with water-blue metachrome-yellow-lactose-agar acc. to Gassner (sensitivity 91.7%) and in 31 cases with brilliant-green-phenol-red-lactose-agar acc. to Kauffmann (sensitivity 86.1%). The high specificity (99.87%) recommends the use of Rambach agar for isolation of Salmonellae from selective enrichment. PMID- 7993336 TI - [Unconventional disease agents--a danger for humans and animals?]. AB - The occurrence of bovine spongiform encephalopathy (BSE) in Great Britain in 1985/86, has focused again the public concern as well as scientific interest to the Scrapie disease of sheep and goat known more than 150 years. The agents of scrapie and BSE are characterized by unusual biological and physical-chemical properties, especially their high tenacity. Therefore, they are also designated "unconventional agents of viruses". Different theories have been proposed about their infectious characteristics--especially because of the apparent or real missing of an agent-specific nucleic acid--which are named Virinos, Prions or Nemavirus. The broad host range of Scrapie respective BSE, which includes domestic and wild ruminants, Suidae, Felidae, Mustelidae, small rodents, birds and non-primates, has created some concern since there might be an aetiological correlation between the transmissible spongiform encephalopathies of man (Creutzfeld-Jakob- and Gerstmann-Straussler-Scheinker-Disease) and that of animals. Although at present neither epidemiological nor molecular biological evidence whatsoever was proved, the hypothesis cannot be completely disproved. The probability of infection through digestive tract seems to be rather unlikely but special precautions should be taken as far as production, investigation and application of human medicine drugs of animal origin. Furthermore, research about the aetiology of "unconventional agents" and pathogenesis of resulting diseases is necessary and should be intensified in Germany. Finally, only an early intra vitam-Diagnose and in vitro detection can avoid an further spread of this new category of diseases. PMID- 7993337 TI - [The effect of the covering of mares during the postpartum heat on the pregnancy rate]. AB - The present study was carried out to investigate the pregnancy rate after covering in the foal heat (Group I), in the subsequent spontaneous heat (Group II), and in the induced heat (Group III) after administration of 7.5 mg of the prostaglandin F2 alpha analogue Luprostiol (Reprodin, Bayer) between the 20th and 22nd day post partum. Breeding during foal heat resulted in a pregnancy rate of 43.9% compared to 48.6% in the subsequent spontaneous heat post partum. Of 18 mares in group III, 14 mares had a foal heat, whereas 4 others had not shown a foal heat. 1-8 days after treatment, 14 mares (77.8%) returned to an oestrus. In consideration of the mares which had shown a foal heat, oestrus was induced in 85.7% of treated mares. In this group, a pregnancy rate of 50.0% was achieved. In conclusion, the results of the present study indicate that induction of oestrus by treatment with prostaglandin 20-22 days after parturition for covering is a good alternative. PMID- 7993338 TI - [Yew poisoning in Australian emus (Dromaius novaehollandiae, LATHAM)]. AB - Six, four month old, captive bred emus (Dromaius novaehollandiae) were found dead in their pen without any previous indications of illness. Postmortem examination revealed the cause of death to be taxine poisoning after ingestion of leaves and green berries from a Yew bush (Taxus baccata) growing outside the perimeter fencing but encroaching through the wire. After longstanding access to the Yew bush, an unidentified stimulus prompted these young birds to sample this toxic plant. Pathological findings included changes in the lungs, heart, liver, spleen and most parts of the digestive system as would be expected from the quoted sources concerning taxine poisoning in other species. Considering the varied artificial environments in which taxa are kept and the relative infrequency of autopsies carried out on birds, the incidence of taxine poisoning in avian species is considered to be probably much higher than that evidenced by reference to the published literature. PMID- 7993339 TI - [Detection of mycoplasmas in horses with respiratory diseases and their biochemical and serologic characterization]. AB - Tracheal swabs were taken from 25 horses with respiratory diseases and investigated for mycoplasmas using three different media. Mycoplasmas could be isolated from 5 horses. The isolates were characterized by serological and biochemical methods. Four isolates could be identified as Mycoplasma equirhinis. The fifth isolate could not be typed. It did not react with antisera against mycoplasmas found in the respiratory tract of horses and its biochemical characteristics were different from the mycoplasmas described so far. It may represent a new species. PMID- 7993340 TI - [The development of veterinary boards and veterinary institutes in Germany in the 18th and 19th centuries]. AB - Coincident with the veterinary institutes at the universities a number of at first smaller institutes were founded, that partly attained a leading role up to this day for scientific and diagnostic work in veterinary medicine. The chambers of veterinarians in the first half of the 19th century were progressive institutions with statutes as modern as today. PMID- 7993341 TI - [The relationship between the acidity of the rumen contents and the proliferation status of the rumen mucosa in cattle]. AB - Two non pregnant, non lactating Jersey cows, fitted with rumen fistulas, were subjected to three feeding periods: high - low - high in energy. At the end of each period biopsies (approximately 1 cm2) were taken from the floor of the dorsal blind sack of the rumen for morphological examination. After in-vivo isolation of the ventral sack of the rumen a mixture of volatile fatty acids (pH 5) has been infused and the time measured in which the pH value rose from 5 to 7. The ruminal mucosa reacted to the different energy levels of the ration, as expected, by proliferation or regression. With high mucosa the pH of the infused solution rose, at the maximum, 100% faster to pH 7 than with low mucosa. On that way the different absorption capacity of the ruminal mucosa as well as their importance for the regulation of the pH value in the rumen could be demonstrated. PMID- 7993342 TI - [The lipopolysaccharide structure of Haemophilus parasuis strains in SDS-PAGE]. AB - The LPS patterns of 231 H.p. strains were studied by using SDS-PAGE. The strains were isolated from the nasal mucous membrane of clinical healthy animals, from animals with GK and from animals with pneumonia without any symptoms of GK. The LPS patterns of H.p. strains consists of 2 to 4 bands of high electrophoretical mobility. In all it was possible to distinguish seven different LPS electrophoretic profiles. The distribution of the H.p. isolates from clinically healthy animals and animals with GK or pneumonia to the 7 LPS electrophoretic profiles shows a similar picture. Variation in the growth conditions showed a process of a standardization of the LPS structure as a result of an increased CO2 atmosphere or lack of O2 respectively. PMID- 7993343 TI - [Therapy of edema disease/coli complex of weaned piglets--where do we stand today?]. AB - The paper gives an up to date review of our knowledge concerning etiology, clinics and pathogenesis of the edema disease. A therapy protocol is given, an extensive list of original literature for further study is presented. PMID- 7993344 TI - [Development and testing of an indirect ELISA for the detection of antibodies against avian encephalomyelitis]. AB - Because of the intensive efforts required and the dissatisfactory sensitivity achieved with the traditional serological diagnostic techniques for Avian Encephalomyelitis, an ELISA was developed and tested to show the presence of antibodies in chicken serum. Using a multi-phase antigen preparation and optimizing the reagents and serum dilutions, a method was developed which shows considerable advantages in sensitivity, specificity, practicability and costs compared with the Embryo Serum Neutralization Test. PMID- 7993345 TI - [Results of serological studies of Leptospira antibodies in foxes]. AB - 1253 serum samples of foxes were checked for the presence of Leptospira antibodies. 24 serum samples (1.92%) were positive. Leptospira grippotyphosa (10 samples) was the most common serotype, which ist also widespread in other wild and domestic animals. The possibility of distribution of Leptospira in fox populations are discussed. Leptospira antibodies were found in only 0.20% of the examined serum samples of domestic animals of the same territory (South Thuringia). PMID- 7993346 TI - [The development of the state veterinary organization in Germany in the 18th and 19th centuries]. AB - The short introduction into the historical development of our profession is followed by a review of the beginning of the public veterinary affairs in Germany of the 18th and 19th century with special respect of Prussia and Bavaria. PMID- 7993348 TI - [Occurrence of Campylobacter and salmonellas in relation to liver changes in slaughtered poultry]. AB - On the occasion of slaughter, 97 laying chickens, 100 broilers, 48 geese and 36 ducks were examined for Campylobacter spp. and Salmonella spp. in liver, small intestine and caeca. Pathological changes in the liver were recorded. Campylobacters and salmonellas were isolated from 61 and 18% of the laying chickens, 63 and 3% of the broilers, 54 and 15% of the geese and from 81 and 39% of the ducks, respectively. Birds with diseased liver were found more often infected with campylobacters and salmonellas than those without. This correlation could be gathered from the isolation rates from the liver and from the intestine. The occurrence of campylobacters and salmonellas together in the liver was only observed in individuals with pathological changes of the liver. The own findings suggest that besides salmonellas also campylobacters can be responsible for diseases of the liver. PMID- 7993347 TI - Antigenic changes in Campylobacter spp. after adaptation to media with increased sodium chloride concentrations. AB - Campylobacter strains which were adapted to growth at 3% NaCl in the medium were examined for antigenic changes. The results of the immunodot blot, the immunoprecipitation test and the immunoblot demonstrate changes in the antigenic pattern. Heat-labile and heat stable antigens of the obtained salt-tolerants variants of Campylobacter type-strains showed differences from their parental strains after cross-absorption of antisera. Differences of the antigens between salt-tolerant variants and their salt-sensitive parental strains suggest that the antigenic structure of the flagellum and possibly of outer membrane proteins has been changed by adaptation of strains to higher salt concentrations. PMID- 7993349 TI - [Illustrated report from practice: foreign body in the bifurcation of the trachea of a dog]. AB - A stone in the bifurcatio tracheae is diagnosed roentgenologically and extracted under endoscopic control. PMID- 7993350 TI - [Continuous production of FMD virus in a two-step bioreactor system]. AB - The so-called Goettingen two step bioreactor system has been tested in a pilot project in Argentina to produce FMD-virus. With a 10-1-reactor a cell density of 3.5-4 x 10(6) cells/ml could be maintained and virus titres of up to 10(7.2) TCID/ml were reached. A correlation existed between inoculum titre and incubation period of virus. With lower inoculum a higher titre of harvested virus and a shorter incubation period were obtained. In spite of considerable problems with peripheral infrastructure and laboratory equipment the bioreactor system did work reliably. The project was terminated before final results of virus yield could be reached. PMID- 7993351 TI - ["With effort and much pain and an unspeakable, truly stupid patience." Theodor Ludwig Wilhelm von Bischoff (1807-1882) as an embryologist]. AB - Theodor L. W. von Bischoff (1807-1882), who worked as an anatomist and physiologist in Heidelberg, Giessen and Munich, is among the most excellent embryologists of the 19th century. His work on the history of development of mammals and of man (1842), his finding proof of spontaneous periodic ovulation in mammals (1844), but above all his directive monographies on rabbits, dogs, guinea pigs and deer (1842-1854) provided the most comprehensive research into the history of the development of mammals which had been done so far. He was less successful, however, with his physiological research including a project on urea as a measure for metabolic activity (1853) which had been initiated by Justus Liebig. The same is true for his studies of the weight of the human brain and his comparative anatomical research into the anatomy of the skull and brain of primates, which had been his main interest since 1860. Bischoff, who had been raised to nobility for his merits, did not confine his activities to science, but engaged in questions of medical education and in the politics of his profession as a member of influential committees, fiercely opposing the admission of women to medical studies (1872). PMID- 7993352 TI - Psychosocial aspects of preventive psychiatry. PMID- 7993353 TI - Decentralization of mental health services in Greece. 1979-82 and 1989-92. PMID- 7993354 TI - Leros deinstitutionalization program: psychopathological parameters in sheltered care residents. PMID- 7993355 TI - The role of psychiatry in the renewal of medical education. PMID- 7993356 TI - Personality characteristics of psychiatric trainees. PMID- 7993358 TI - Civilization and mental health: suggestions for a foundation of the concepts. PMID- 7993357 TI - Preventing adult psychopathology with interventions in childhood. PMID- 7993359 TI - The preventive effect of early interventions. PMID- 7993360 TI - School drop-outs in Greece: is it true that Greek adolescents reject school? PMID- 7993361 TI - Prevention of postnatal mental illness: sociocultural facets. PMID- 7993363 TI - Self-destructive behaviour: risk factors and preventive principles. PMID- 7993362 TI - Prevention of postoperative anxiety and depression. PMID- 7993364 TI - Suicides in a large psychiatric hospital: risk factors for schizophrenic patients. PMID- 7993365 TI - Treatment of recurrent unipolar depressions: psychological and biological aspects. PMID- 7993367 TI - Maintenance antipsychotic therapy and civil commitment. PMID- 7993366 TI - Genetic counseling for major psychiatric disorders. PMID- 7993368 TI - Greek psychiatric reform: perspectives and limitations. PMID- 7993369 TI - Problems in tertiary prevention: then and now. PMID- 7993370 TI - Biochemical genetics of methylglyoxal dehydrogenases in the laboratory rat (Rattus norvegicus). AB - A genetic locus controlling the electrophoretic mobility of a methylglyoxal dehydrogenase (EC 1.2.1.23) in the rat is described. The locus, designated Mgd1, is expressed in liver and kidney. Inbred rat strains have fixed either allele Mgd1a or allele Mgd1b. Codominant expression is observed in heterozygotes, providing evidence for a tetrameric enzyme structure. Backcross progenies showed the expected 1:1 segregation ratio, and there is evidence that Mgd1 is linked to Pep3 and Fh1 on chromosome 13. There is also evidence for two additional methylglyoxal dehydrogenases: Mgd2, present in liver and kidney, and Mgd3, present only in heart. PMID- 7993371 TI - Genetic control of geranial formation in Perilla frutescens. AB - A novel chemotype (C type) having a lemon-like odor segregated out in the F2 progeny of a cross between PK and PL chemotypes of Perilla frutescens. Chemical analysis of C-type plants revealed that geranial was the major component of essential oils in the leaves. Genetic analysis suggested that geranial is accumulated by individuals homozygous for two pairs of recessive, polymeric genes, fr1 and fr2, which are incapable of converting geranial into perillene. PMID- 7993373 TI - The identification of nuclear and mitochondrial genes by sequencing randomly chosen clones from a marsupial mammary gland cDNA library. AB - To increase the number of genes that can be mapped to the genome of the tammar wallaby (Macropus eugenii), we sequenced 100 randomly chosen clones from a mammary gland cDNA library. Provisional identifications were made of seven nuclear genes and one mitochondrial gene encoding two caseins, beta galactosidase, acetyl-coenzyme A synthetase, lipoprotein lipase, inorganic pyrophosphatase, an ATP-dependent RNA helicase, and cytochrome c oxidase I. Highly conserved genes, such as that encoding acetyl-coenzyme A synthetase, were easily identified even from cross-kingdom matches. Genes which are highly divergent, however, such as those encoding the mature casein peptides, could not be aligned with homologues in the databases. Even in an organ where there is high mRNA species redundancy, the sequence characterization of expressed sequence tags provides a rapid means of gene identification for mapping purposes. PMID- 7993372 TI - Molecular heterogeneity of naturally occurring sn-glycerol-3-phosphate dehydrogenase low-activity variants in Drosophila melanogaster. AB - Northern analyses of two low-activity sn-glycerol-3-phosphate dehydrogenase (Gpdh) alleles extracted from natural populations of Drosophila melanogaster showed that one of them, GpdhACyg22, produced wild-type levels of a normal sized (1.7-kb) mRNA but the other, GpdhAMB5, had very low levels of a 1.7-kb mRNA together with low levels of a transcript 200 bp larger. The two variant genes were cloned and sequenced. Compared with normal activity alleles, there were two nucleotide differences in the DNA sequence of GpdhACyg22 which were in first codon positions and would be expected to give rise to Asn-13-->Tyr and Arg-272- >Cys substitutions. The second of these changes is most likely to account for the altered properties of the enzyme. In contrast, none of the nucleotide differences in GpdhAMB5 would give rise to amino acid substitutions, but a 76-bp deletion in the 5' region removed the normal TATA box and there was a 20-bp insertion in the same region. One of the two transcripts was derived from the use of a substitute TATA box sequence in the insertion, but the 1.9-kb transcript had heterogeneous 5' ends that were not associated with substitute TATA box sequences. The two transcripts either are produced at a lower rate or are less stable than the normal mRNA. PMID- 7993374 TI - Alcohol dehydrogenase (EC 1.1.1.1) isozymes as markers at 2,4 dichlorophenoxyacetic acid x kinetin combinations in callus cultures of Cereus peruvianus (Cactaceae). AB - Alcohol dehydrogenase (ADH; EC 1.1.1.1) isozymes were investigated in tissue of Cereus peruvianus cultured in different concentrations of 2,4 dichlorophenoxyacetic acid (2,4-D) and kinetin. Five ADH isozymes were detected in starch gel and showed different patterns in seeds, seedlings, calli cultured at 32 and 22 degrees C, and plants regenerated from calli cultured in three 2,4-D and kinetin combinations. Four phenotypes formed by different combinations of ADH 2, ADH-3, ADH-4, and ADH-5 were detected in calli cultured at 32 degrees C and in plants regenerated from calli. ADH-1 isozyme was detected only in calli subcultured for 1 or 2 weeks at 22 degrees C and was indicated as a marker of stress conditions that affect the growth of C. peruvianus callus tissues in culture. ADH phenotypes with either a higher or a lower number of isozymes were detected in different proportions in the callus tissues cultured in media containing different 2,4-D and kinetin ratios. ADH isozyme patterns were found to be sensitive markers at the highest kinetin concentration or at high kinetin/2,4 D ratios. The results indicate a high correlation between the ADH isozyme patterns and the capacity for regeneration. Thus, ADH isozymes are indicated as good biochemical markers and as a powerful tool for monitoring studies of C. peruvianus callus cultures. PMID- 7993375 TI - Molecular genetics of chimpanzee Rh-related genes: their relationship with the R C-E-F blood group system, the chimpanzee counterpart of the human rhesus system. AB - As the chimpanzee R-C-E-F blood group system appears to be the chimpanzee counterpart of the human Rhesus (RH) system, we have tried to determine whether chimpanzee Rh-like genes encode R-C-E-F-related proteins. Chimpanzee genomic DNA, digested by any of eight endonucleases and hybridized with three Rh exon-specific probes, exhibits a high degree of polymorphism. Analysis of DNA from unrelated individuals of different R-C-E-F types revealed that the presence of some restriction fragments is correlated with particular R-C-E-F types. The cosegregation of these fragments with R-C-E-F haplotypes was confirmed by family studies. Oligonucleotides complementary to regions flanking human exons were used as PCR primers on chimpanzee DNA; the resulting amplified fragments were identical in size to their human counterparts. Moreover, the nucleotide sequences of the fragments present a high degree of similarity to the corresponding human regions. PMID- 7993376 TI - Construction of genetic maps for some Eurasian coniferous species using allozyme genes. AB - In an analysis of allozyme genes in three pine and one spruce species distributed in Eurasia, 45 of 87 loci were mapped. Four linkage groups in Pinus sylvestris and Picea abies, three in Pinus pallasiana, and two in Pinus pumila were determined. The order and the locations of homologous genes in the linkage groups in the different species were similar. The data suggest that during the separate development of the Pinus and Picea genera that has lasted for millions of years, there was not any large inversion, translocation, or other significant chromosomal change, at least in the gene blocks analyzed. PMID- 7993377 TI - [Noninstrumental immunoanalysis based on dyed polyacrolein latexes. Determination of a group-specific polysaccharide from Streptococcus pyogenes]. AB - Non-instrumental immunoassays based on immunofiltration and microtiter particle agglutination (MPA) techniques have been developed using coloured polyacrolein latex. These methods have been applied to the quantification of the group specific polysaccharide (PS) of S. pyogenes (group A streptococcus) and compared with standard ELISA tests. The most efficient method was MPA; as little as 0.05 ng A-PS/ml could be detected in 1.5 h. In comparison with ELISA test, the sensitivity of MPA was 10 times higher and the procedure was much simpler. The sensitivity of immunofiltration assay using both enzyme and latex conjugates was shown to be the same (50 ng/ml A-PS) and the duration of the assay 3-5 min. No cross-reactions of latex conjugates with non A streptococcus cell lysates have been observed. The developed methods are rapid, robust, easy to perform, don't need any sophisticated equipment and specially trained staff. PMID- 7993378 TI - [Synthesis and biological activity of new analogs of beta-casomorphine-5]. AB - Four new analogues of beta-cazomorphine-5 modified at the C-end with ethylenediamine- and glycine-containing derivatives were synthesized by the standard method of peptide chemistry (mixed anhydrides, carbodiimide, activated esters): H-Tyr-Pro-Phe-Pro-Gly-EtDA-Gly-II (I) H-Tyr-Pro-Phe-Pro-Gly-EtDA-Gly-Gly II (II) H-Tyr-Pro-Phe-Pro-Gly-EtDA-Gly-Gly-CO-CH3 (III) H-Tyr-Pro-Phe-Pro-Gly EtDA-Gly-Gly-CO-CH2-CH2-COOH (IV) The level of affinity and the degree of selectivity of the peptides towards the mu- and delta-opioid receptors of the rat brain lyophilized membranes were studied by the radioreceptor method. All the new peptides displayed analgetic activity, largely depending upon their structure. PMID- 7993379 TI - [Cloning transport protein genes for two strains of tobacco mosaic virus and their expression in Escherichia coli cells]. AB - Recombinant constructs expressing fusion (His)6 movement proteins of two strains (Cruciferous and Vulgare) of tobacco mosaic virus were generated by cloning the PCR-amplified fragments into the pQE-9 vector. The movement proteins containing N terminal (His)6 affinity tags were purified on a metal chelate adsorbent. PMID- 7993380 TI - [Synthesis and cloning of genes for the antisense peptides for human calcitonin and miniproinsulin]. AB - Because of the potential significance of the 'molecular recognition' theory for studies in molecular biology and biotechnology, the theory is worth being examined using methods of chemical-enzymatic gene synthesis, recombinant DNA construction and microbiological peptide synthesis. We therefore undertook the synthesis of human Va18-calcitonin, miniproinsulin, and the corresponding antisense peptides as model compounds. In designing an experimental system the idea was to combine sense and antisense polypeptides into a single chain and to examine their intramolecular interaction. In this paper the chemical-enzymatic synthesis, cloning and expression of the genes for calcitonin, miniproinsulin, the corresponding antisense peptides and their combinations are described. The recombinant DNAs obtained were able to direct in vivo expression of the target polypeptides as hybrid proteins with the IgG-binding domain of the staphylococcal A protein in bacterial cells. PMID- 7993382 TI - American Speech-Language-Hearing Association. 1994 annual convention. New Orleans, Louisiana, November 17-21, 1994. Abstracts. PMID- 7993381 TI - [Native, modified, and immobilized chymotrypsin in chaotropic media. Stabilization limits]. AB - To stabilize alpha-chymotrypsin against irreversible thermal inactivation at high temperatures, methods of covalent modification and multi-point immobilization in combination with the addition of salting-in compounds were used. The upper limit of the protein stability proved to be the same for a combination of the modification and salting-in media and for each of these methods separately. The limit of stabilization reached by means of covalent immobilization is higher than the limit of stabilization reached by two other methods. The greatest stabilization of immobilized alpha-chymotrypsin by the salting-in media (a 10000 fold increase in the native enzyme's stability level) takes place only in the case of the protein with the minimum number of bonds with the support. Stabilization of the enzyme by these methods is explained in terms of the suppression of the conformational inactivation processes. PMID- 7993383 TI - An accident and emergency department experience. PMID- 7993384 TI - The right gastroepiploic artery graft. Clinical and angiographic midterm results in 200 patients. AB - From March 1986 to September 1991, the right gastroepiploic artery has been used for coronary artery bypass grafting in 200 patients (171 male and 29 female patients, mean age 58 years, range 6 to 80 years. They were followed up from 6 to 70 months with a mean of 27 months. There were 16 reoperations and 176 patients had triple vessel or left main disease. The gastroepiploic artery (182 in situ and 18 free grafts) was anastomosed to 11 anterior descending, 3 diagonal, 26 circumflex, and 160 right coronary arteries. The internal thoracic artery was concomitantly used in 192 patients. The mean number of distal anastomoses was 2.3 with arterial grafts and 3.3 including additional saphenous vein grafts. Postoperative angiography was performed in 152 patients within 6 months after the operation (mean 2 months) and after the operation second angiograms were done sequentially 1 to 5 years (mean 2 years) after the operation in 40 patients. There were 6 early and 4 late deaths. A new Q wave was noted in 4 patients. Duration of the operation and postoperative complications did not increase with the use of the gastroepiploic artery. Relief of angina was noted in 186 patients. Gastroepiploic artery graft patency was 95% (144/152) in the early postoperative period and 95% (38/40) in the late postoperative period. Percutaneous transluminal coronary angioplasty was done successfully through the in situ gastroepiploic artery graft for anastomotic stenosis in four cases. In stress myocardial scintiscans, performed sequentially preoperatively and in the immediate, 1-year, and 2-year postoperative periods in 11 patients, washout rate of the gastroepiploic artery-grafted area improved from 35% +/- 10% to 45% +/- 15% (p < 0.05) and was maintained to 43% +/- 6% and 48% +/- 9% at respective periods. In conclusion, the gastroepiploic artery is a suitable conduit for coronary artery bypass grafting in terms of low surgical risk, high patency rate, and excellent patient outcome. PMID- 7993385 TI - Public discourse on the benefits of moderation: implications for alcohol policy development. AB - There is increasingly widespread acceptance of a protective effect of alcohol against coronary heart disease and a consequent delay of mortality among the elderly. This information has been widely disseminated in the popular media and by industry related sectors. The policy arguments based on the epidemiological data are that moderate alcohol use is beneficial, therefore policy should not impact on moderate drinkers, only on heavy drinkers. This fits well with the arguments of those opposed to population public health measures such as taxation, controls on availability, and enforcement of drink-driving laws like random breath testing. However, there is a growing consensus among public health researchers that population measures are most effective at reducing alcohol related harm. Concern has been expressed that the current public discourse on benefits of moderation will influence individuals to drink more. Of equal, or even greater, concern is the likelihood that this public discourse will decrease the chances that effective population focused policies will be implemented. PMID- 7993386 TI - Increased levels of cow's milk and beta-lactoglobulin antibodies in young children with newly diagnosed IDDM. The Childhood Diabetes in Finland Study Group. AB - OBJECTIVE: To investigate the humoral immune response to cow's milk in pediatric patients with newly diagnosed IDDM. RESEARCH DESIGN AND METHODS: We measured IgA, IgG, and IgM antibodies to the proteins of cow's milk and to beta-lactoglobulin by an enzyme-linked immunosorbent assay. Samples from 706 pediatric patients with newly diagnosed IDDM were available. We used two comparison groups: 105 patients < 7 yr old had an unrelated age-matched control subject, and samples from 456 3- to 14-yr-old nondiabetic siblings also were available. RESULTS: Patients < 3 yr of age had a markedly higher median level of IgG and IgA antibodies to cow's milk compared with the control subjects (P = 0.03 and 0.002, respectively), IgG antibodies to beta-lactoglobulin also were higher (P = 0.03). Older groups of diabetic patients, 3.0-6.9 and 7.0-14.9 yr of age, had significantly higher levels of IgA antibodies to cow's milk and beta-lactoglobulin than the age matched comparison groups of both unrelated control subjects and nondiabetic siblings, although the median values of the diabetic patients were closer to those of the comparison groups than in the youngest groups. Nondiabetic siblings had higher levels of IgA cow's milk antibodies than unrelated control subjects of similar ages (3-6.9 yr of age) (P = 0.03). The 14 siblings contracting IDDM during the follow-up showed no change in the levels of cow's milk or beta lactoglobulin antibodies in relation to the clinical diagnosis. CONCLUSIONS: The results indicate an abnormally strong humoral response to the proteins of cow's milk, particularly in young IDDM patients and, to a lesser extent, in their siblings. We infer that the proteins of cow's milk may trigger the autoimmune process of IDDM. PMID- 7993387 TI - Improved visualization of the choroidal circulation with indocyanine green angiography. PMID- 7993389 TI - Investigation of a thrombin inhibitor peptide as an alternative to heparin in cardiopulmonary bypass surgery. AB - BACKGROUND: This study was undertaken to determine if a newly developed synthetic peptide thrombin inhibitor (DuP 714; DuPont-Merck, Wilmington, Del) could be used as an anticoagulant in cardiopulmonary bypass (CPB) surgery. METHODS AND RESULTS: Anesthetized mongrel dogs were placed on CPB for 1 hour and then observed for 2 hours. Following a dose-finding study, the optimal dose (DuP 714 group) and an overdose (DuP-HI group) were studied. The DuP 714 group received 0.25 mg/kg i.v. bolus plus 0.5 mg.kg-1 x h-1 infusion of DuP 714 (n = 10) and the DuP-HI group received 0.5 mg/kg i.v. bolus plus 1.0 mg.kg-1 x h-1 infusion of DuP 714 (n = 6). No neutralizing agent was used. The control group received 2.0 mg/kg intracardiac bolus of heparin with 0.15 mg/kg i.v. bolus injections as needed to maintain the activated clotting time (ACT) at > 300 seconds during CPB (n = 6). Protamine sulfate (2.0 mg/kg) was used to reverse heparin after CPB. Postoperative blood loss for both DuP 714 groups was less than that for heparin (177 +/- 40 and 297 +/- 36 versus 318 +/- 99 g, P = NS). The DuP 714 group revealed higher pump line filter fibrin deposits (15.5 +/- 3.6 mg, P < .032 ANOVA) compared with the heparin group (4.2 +/- 2.4 mg), whereas the DuP-HI group showed equivalent deposits (9.3 +/- 5.3 mg). The ACT levels recorded during and 30 minutes after CPB were 638 +/- 52 and 160 +/- 9 seconds in the DuP 714 group and > 800 and 436 +/- 75 seconds in the DuP-HI group; however, the ACT level only in the DuP-HI group remained elevated 2 hours after CPB. Platelet counts were significantly higher (P < .05) in both DuP 714 groups after CPB. There was nearly complete elimination of all peptide in the urine. No statistical difference was observed in hemodynamics (cardiac index and systemic vascular resistance) in any of the groups. CONCLUSIONS: This study reveals that the peptide inhibitor DuP 714 can effectively function as an anticoagulant in a canine CPB model. The efficacy and safety, even when overdosed, are demonstrated by reduced blood loss and lack of platelet count reduction. Clinical monitoring can be achieved by the use of ACT levels. No evidence of hemodynamic compromise was noted with the drug administration. PMID- 7993388 TI - Postoperative pain management and acute pain service activity in Canada. AB - A survey of postoperative pain management practices was mailed to the 56 Canadian university-affiliated teaching hospitals in December 1991. The aims of the survey were (1) to determine the prevalence, structure, and function of Acute Pain Services and (2) to determine the use and management of patient-controlled analgesia (PCA) and epidural opiate analgesia (EOA) in teaching hospitals. Responses were received from 47 hospitals, representing a return rate of 84%. Twenty-five hospitals (53%) operated an Acute Pain Service and an additional 17 (35%) were attempting to organize one. "Time commitment" was given as the primary reason why hospitals were unable to offer an Acute Pain Service. Most commonly used methods of pain relief were EOA and PCA. Most services were multidisciplinary, with 60% having a nurse and 29% a pharmacist. Irrespective of the presence of an Acute Pain Service, PCA was used at 32 (68%) hospitals, and EOA was used at 41 (87%); however, only 15 provided EOA on general wards. Complications have occurred with both PCA and EOA, with 14 of 32 hospitals indicating that they have had a major or serious complication. The data suggest an estimated incidence of severe respiratory depression of 0.03% with PCA and 0.13% with EOA. No deaths were reported at the time of the survey. Epidural opioid-local anaesthetic EOA-LA combinations were used at 26 (63%) hospitals; however, only six administered these combinations on general words. We conclude that a multidisciplinary team approach to manage postoperative pain is viable in university teaching hospitals of all sizes.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7993391 TI - Properties of aminopeptidase activity involved in the conversion of vasopressin by rat brain membranes. AB - Previously it has been shown that vasopressin (VP) and oxytocin are converted by aminopeptidase activity in brain membranes into fragments with potent CNS activities. This report concerns the properties of this enzyme activity, addressed as VP-converting aminopeptidase (VP-AP) activity, in membranes of the rat brain. The VP-AP activity had a pH optimum at pH 7.0 and had a Km of 17 microM for its action on VP. Amastatin was the most potent aminopeptidase inhibitor. Enzyme activity was inhibited by relatively low concentrations of metal chelators. Treatment of brain membranes by EDTA resulted in loss of enzyme activity that was completely reversed by 10 microM Zn2+, indicating that VP-AP activity is a metallopeptidase. Several VP analogues and fragments, in particular VP(1-8), inhibited the action of enzyme activity on VP. Among peptides unrelated to VP, angiotension I, somatostatin, and porcine ACTH(1-39) markedly inhibited enzyme activity. Solubilization of VP-AP activity from brain membranes and gel filtration on Sephadex G200 showed two peaks of activity, one eluting with an apparent mass of about 140 kDa, the other in the void volume. Gel filtration fractions were able to convert [3H][Phe3]VP in a step-wise fashion. The VP-AP like activity was found in many tissues outside the brain. Highest activity was present in lung, kidney, parts of the gastrointestinal tract, ovary, and uterus. The results indicate that VP-AP activity is a widely distributed enzyme with probably multiple functions, one of which involves the metabolism of vasopressin in the brain. PMID- 7993390 TI - P1 and cosmid clones define the organization of 280 kb of the mouse H-2 complex containing the Cps-1 and Hsp70 loci. AB - A 280 kilobase (kb) contig was isolated from mouse genomic P1 and cosmid libraries, using as probes human cDNA and genomic DNA fragments that map in the interval between the second component of complement and tumor necrosis factor genes of the HLA complex. The clone contig demonstrates synteny of eleven mouse genes that are homologous to genes initially mapped within the human major histocompatibility complex. These include the mouse homologs of BAT2 (HLA-B associated transcript 2) through BAT9 and also three HSP70-related genes. Five P1 clones form a contig of 240 kb that spans from BAT9 through BAT3. Twelve cosmid clones are arranged in three contigs that confirm most of the structure of the P1 contig and link the mouse BAT3 homolog to the BAT2 homolog approximately 15 kb farther telomeric. Polymorphic DNA markers within the cloned region were used to map the cleft palate susceptibility-1 (Cps-1) locus to the interval between Hsp70.1 and BAT6 (valyl-tRNA synthetase). This refines the location of the Cps-1 locus to a 45 kb region contained in the H2-124 P1 insert. PMID- 7993392 TI - GroESL proteins facilitate binding of externally added inducer by LuxR protein containing E. coli cells. AB - htpR- (rpoH, sigma 32 minus) strain of E. coli harbouring the whole lux system of Vibrio fischeri is very dim. We have recently shown that GroESL proteins fully recover the expression of the lux system in this strain. This work has been undertaken to study our assumption that the GroESL proteins stabilize the LuxR protein, thus enhancing the formation of LuxR-Inducer complex. E. coli htpR- cells harbouring the luxR gene were unable to bind extracellularly added inducer, while late logarithmically growing htpR+ strain bound small quantities of the inducer. Reduction in the nutrient content of the growth medium resulted in a large increase in the capability of these cells to bind the inducer. htpR+ or htpR- E. coli strains harbouring both the luxR and the groESL genes bound large quantities of the inducer. The molecular and ecological significance of these results is discussed. PMID- 7993393 TI - Patellofemoral pain syndrome. AB - Patellofemoral pain syndrome is a common problem that occurs in association with mild malalignment of the extensor mechanism of the knee or as a result of repetitive microtrauma from overuse. Patients most often present with retropatellar or peripatellar knee pain, which becomes especially noticeable when they climb or descend stairs. The diagnosis is usually made from the history and the physical examination, with relatively little information gained from other diagnostic aids. Treatment involves physical therapy, anti-inflammatory medication and the application of ice. In most patients, surgical treatment should be avoided. Patient motivation and adherence to the treatment regimen are critical to long-lasting improvement. PMID- 7993394 TI - Characterization of linne, a new autosomal eclosion rhythm mutant in Drosophila subobscura. AB - A new putative gene, named linne, affecting circadian eclosion rhythm was found in a Norwegian strain of Drosophila subobscura. The phenotype of linne may be novel among Drosophila clock mutants. Eclosion is practically arrhythmic in light dark cycles, but diel temperature cycles of 4 degrees C amplitude effectively entrain eclosion in continuous light and in continuous darkness. After that, the rhythm continues in constant temperature and darkness, but unlike other strains, it continues in constant temperature and light as well. Thus in the linne strain the coupling between light signals and pacemaker is disrupted, not the pacemaker itself. Genetic effects of linne were tested in crosses with a wild strain. Arrhythmicity was recessive and autosomal and showed monogenic inheritance, suggesting that arrhythmicity in linne is based on mutation on a single locus. PMID- 7993395 TI - Investigation of a fatality from nonoccupational aluminum phosphide exposure: measurement of aluminum in tissue and body fluids as a marker of exposure. AB - This case study reports our clinical and laboratory investigation of the accidental death of a pregnant rural woman related to phosphine exposure from stored grain fumigated with aluminum phosphide (AIP3) pellets. Environmental data (housing proximity to fumigated grain and meteorologic conditions at the time) coupled with clinical data (tachycardia and the rapid development of pulmonary edema with no antecedent clinical abnormalities) suggested possible toxicant effects. Gross and microscopic autopsy findings demonstrated pulmonary edema. Because phosphine generated from the phosphide is highly reactive and unstable, our laboratory strategy for this investigation focused on the quantitative analysis of aluminum (AI) in blood, gastric contents, and in lung tissue to test the possibility of fumigant intoxication. We recovered 713 ng/ml Al from blood (normal laboratory range 2 to 42 ng/ml). Laser mass spectral analysis of lung tissue demonstrated high concentrations of Al in alveolar macrophages (> 200 ppm) with little or no Al in adjacent lung tissue. Control lung tissue from an urban autopsy case matched by age, sex, and smoking habits showed no demonstrable Al. We conclude that Al may be a useful marker for AIP3 exposure. PMID- 7993396 TI - Transnasal butorphanol. AB - Transnasal administration of systemic medication offers a convenient alternative to intravenous and intramuscular routes. Butorphanol, a noncontrolled, synthetic opioid agonist-antagonist analgesic is available in a nasal spray formulation. Transnasal butorphanol appears to be a safe and effective alternative for the treatment of moderate to severe postoperative and migraine headache pain. Side effects include sedation, nausea and confusion; transnasal butorphanol also has the potential to induce abstinence syndromes in opioid-dependent patients. PMID- 7993397 TI - Malignant pilomatrixoma with bone metastasis. PMID- 7993398 TI - Obesity as an adaptation to a high-fat diet: evidence from a cross-sectional study. AB - Expansion of the fat stores has been proposed as a prerequisite for increasing fat oxidation in response to a high-fat diet in individuals with a predisposition to obesity. In a cross-sectional design we measured 24-h substrate oxidations on a standardized diet in 38 overweight or obese and 35 nonobese women. Fat oxidation (g/d) was mainly a function of total energy requirements (r = 0.71, P < 0.0001). To account for this we used for further analysis oxidative fat energy (%), a counterpart to dietary fat energy (%). After differences in fat energy of consumed food (%), age, and 24-h energy balance were adjusted for, obese women had higher oxidative fat energy than did nonobese women [40.2% (37.8-42.6) vs 36.0% (33.6-38.5), P < 0.02]. Adjusted oxidative fat energy (%) increased with increasing size of fat mass (r = 0.31, P < 0.01). This relation suggests that a 10-kg change in fat mass may be caused by a change in dietary fat energy of > or = 1.6% (0.4-2.7%). The study supports the concept that in susceptible individuals the expansion of fat stores is a prerequisite to increase the oxidative fat energy to an amount commensurate with a high percentage of dietary fat energy. PMID- 7993399 TI - The nucleus is insulated from large cytosolic calcium ion changes. AB - Extracellular events regulate functions in the cell nucleus by means of calcium ions acting through effector enzymes. Recently, the traditional view of the nuclear pore as freely permeable to small ions has been questioned as a result of reports that nuclear calcium can be regulated independently of cytosolic calcium. We have used confocal microscopy of fluorescent Ca2+ indicators to investigate the Ca2+ dynamics between cytosol and nucleus in neurons. We find that a previously reported amplification of Ca2+ changes in the nucleus is a measurement artefact. Small changes of cytosolic Ca2+ cause equally rapid changes in nuclear Ca2+, consistent with the free diffusion of Ca2+ through nuclear pores. In contrast, large cytosolic Ca2+ increases (above 300 nM) are attenuated in the nucleus. Our results show the nuclear envelope shapes but does not block the passage of Ca2+ signals from cytosol to nucleus. PMID- 7993400 TI - A percutaneous method for venovenous bypass in liver transplantation. PMID- 7993401 TI - Safety hazard--Sabex drug labels. PMID- 7993402 TI - The International Agency for the Prevention of Blindness. PMID- 7993403 TI - Impairment of consciousness induced by valproate treatment following neurosurgical operation. AB - Eight patients, who underwent neurosurgery for various supratentorial lesions presented unexplained impairment of consciousness during the first post-operative days. These states ranged from stupor to deep coma, and two patients had an emergency re-exploration. All these patients were receiving the usual dosage (1000 to 1500 mg per day) of Valproic acid (VPA). The treatment had been initiated either several weeks or months previously in 4 cases, and was thus well tolerated, or the day before surgery in the 4 other cases. EEG recordings displayed diffuse abnormalities, delta waves and/or high voltage triphasic complexes, that led to the diagnosis of VPA intolerance and drug withdrawal. Then full clinical recovery and EEG clearing occurred within 1 to 5 days. VPA intolerances are wellknown but remain exceptional, about 1 case per 100.000. In our neurosurgical population, however, the rate was higher, approximately 2%. Wide areas of blood brain barrier destruction may contribute to the higher frequency of this easily reversible cause of post-operative stupor or coma. PMID- 7993405 TI - Body iron stores and the risk of coronary heart disease. AB - BACKGROUND: Recent studies have suggested an association between higher body iron stores and the risk of coronary heart disease. To assess these findings, we examined the association between transferrin saturation and the risk of coronary heart disease, myocardial infarction, overall mortality, and mortality from cardiovascular causes in a large population. METHODS: We studied a total of 4518 men and women from the first National Health and Nutrition Examination Survey Epidemiologic Follow-up Study, using a multivariate Cox proportional-hazards model. Base-line data were collected from 1971 to 1974, with follow-up through 1987. Transferrin saturation (serum iron concentration divided by total iron binding capacity) was used as a measure of the amount of circulating iron available to tissues. RESULTS: The risk of coronary heart disease was not related to transferrin-saturation levels in white men or women. Estimates of the relative risk of coronary heart disease for the fifth quintile of transferrin saturation as compared with the first quintile were 0.72 (95 percent confidence interval, 0.51 to 1.00) for men and 0.85 (95 percent confidence interval, 0.60 to 1.21) for women. The results were similar for myocardial infarction. A significant inverse association with transferrin saturation was found for overall mortality and for mortality from cardiovascular causes in white men and women. Transferrin saturation was not associated with any of the clinical outcomes in blacks, possibly owing to the small sample. CONCLUSIONS: Higher transferrin-saturation levels were not associated with an increased risk of coronary heart disease or myocardial infarction. On the contrary, the results indicate that there may be an inverse association of iron stores with overall mortality and with mortality from cardiovascular causes. PMID- 7993404 TI - Inhaled nitric oxide in severe acute respiratory failure--its use in intensive care and description of a delivery system. PMID- 7993406 TI - Sex differences in patterns of drug taking behaviour. A study at a London community drug team. AB - This study investigates sex differences in patterns of drug taking and related injecting and sexual behaviour among 355 patients attending a London community drug team. The majority of cases attending the service presented with heroin problems. Men were more likely to use heroin by injection and women were more likely to use heroin by inhaling/smoking ('chasing the dragon'); there was no sex difference in the overall incidence of needle sharing. The delay between first use of the problem drug and first presentation to services was the same for both men and women. Women were more likely to have a sexual partner who was a drug user and to be living with another user than men. This closer social attachment to other drug users was seen as presenting a high risk factor for women with regard to prognosis and treatment. PMID- 7993407 TI - Brief report: molecular biology and the early detection of carcinoma of the bladder--the case of Hubert H. Humphrey. PMID- 7993408 TI - Preventive health services in adults. PMID- 7993409 TI - Mortality in sickle cell disease. Life expectancy and risk factors for early death. AB - BACKGROUND: Information on life expectancy and risk factors for early death among patients with sickle cell disease (sickle cell anemia, sickle cell-hemoglobin C disease, and the sickle cell-beta-thalassemias) is needed to counsel patients, target therapy, and design clinical trials. METHODS: We followed 3764 patients who ranged from birth to 66 years of age at enrollment to determine the life expectancy and calculate the median age at death. In addition, we investigated the circumstances of death for all 209 adult patients who died during the study, and used proportional-hazards regression analysis to identify risk factors for early death among 964 adults with sickle cell anemia who were followed for at least two years. RESULTS: Among children and adults with sickle cell anemia (homozygous for sickle hemoglobin), the median age at death was 42 years for males and 48 years for females. Among those with sickle cell-hemoglobin C disease, the median age at death was 60 years for males and 68 years for females. Among adults with sickle cell disease, 18 percent of the deaths occurred in patients with overt organ failure, predominantly renal. Thirty-three percent were clinically free of organ failure but died during an acute sickle crisis (78 percent had pain, the chest syndrome, or both; 22 percent had stroke). Modeling revealed that in patients with sickle cell anemia, the acute chest syndrome, renal failure, seizures, a base-line white-cell count above 15,000 cells per cubic millimeter, and a low level of fetal hemoglobin were associated with an increased risk of early death. CONCLUSIONS: Fifty percent of patients with sickle cell anemia survived beyond the fifth decade. A large proportion of those who died had no overt chronic organ failure but died during an acute episode of pain, chest syndrome, or stroke. Early mortality was highest among patients whose disease was symptomatic. A high level of fetal hemoglobin predicted improved survival and is probably a reliable childhood forecaster of adult life expectancy. PMID- 7993410 TI - Asymptomatic hepatitis C infection. More questions than answers. PMID- 7993411 TI - Detection of a 4-bp insertion (CACA) functional polymorphism at nucleotide 241 of the cellular adhesion regulatory molecule CMAR (formerly CAR). PMID- 7993412 TI - Transmission of tuberculosis in New York City. An analysis by DNA fingerprinting and conventional epidemiologic methods. AB - BACKGROUND: The incidence of tuberculosis and drug resistance is increasing in the United States, but it is not clear how much of the increase is due to reactivation of latent infection and how much to recent transmission. METHODS: We performed DNA fingerprinting using restriction-fragment-length polymorphism (RFLP) analysis of at least one isolate from every patient with confirmed tuberculosis at a major hospital in the Bronx, New York, from December 1, 1989, through December 31, 1992. Medical records and census-tract data were reviewed for relevant clinical, social, and demographic data. RESULTS: Of 130 patients with tuberculosis, 104 adults (80 percent) had complete medical records and isolates whose DNA fingerprints could be evaluated. Isolates from 65 patients (62.5 percent) had unique RFLP patterns, whereas isolates from 39 patients (37.5 percent) had RFLP patterns that were identical to those of an isolate from at least 1 other study patient; the isolates in the latter group were classified into 12 clusters. Patients whose isolates were included in one of the clusters were inferred to have recently transmitted disease. Independent risk factors for having a clustered isolate included seropositivity for the human immunodeficiency virus (HIV) (odds ratio for Hispanic patients, 4.31; P = 0.02; for non-Hispanic patients, 3.12; P = 0.07), Hispanic ethnicity combined with HIV seronegativity (odds ratio, 5.13; P = 0.05), infection with drug-resistant tuberculosis (odds ratio, 4.52; P = 0.005), and younger age (odds ratio, 1.59; P = 0.02). Residence in sections of the Bronx with a median household income below $20,000 was also associated with having a clustered isolate (odds ratio, 3.22; P = 0.04). CONCLUSIONS: In the inner-city community we studied, recently transmitted tuberculosis accounts for approximately 40 percent of the incident cases and almost two thirds of drug-resistant cases. Recent transmission of tuberculosis, and not only reactivation of latent disease, contributes substantially to the increase in tuberculosis. PMID- 7993414 TI - The quackery question. PMID- 7993413 TI - Elevation of systemic oxygen delivery in the treatment of critically ill patients. AB - BACKGROUND: Elevation of systemic oxygen delivery and consumption has been associated with an improved outcome in critically ill patients. We conducted a randomized trial to determine whether boosting oxygen delivery by infusing the inotropic agent dobutamine would improve the outcome in a diverse group of such patients. METHODS: On the basis of previously published recommendations, we established the following goals: a cardiac index above 4.5 liters per minute per square meter of body-surface area, oxygen delivery above 600 ml per minute per square meter, and oxygen consumption above 170 ml per minute per square meter. If these goals were not achieved with volume expansion alone, patients were randomly assigned to a treatment or control group. The treatment group received intravenous dobutamine (5 to 200 micrograms per kilogram of body weight per minute) until all three goals had been achieved. Dobutamine was administered to the control group only if the cardiac index was below 2.8 liters per minute per square meter. RESULTS: A total of 109 patients were studied. In nine patients the therapeutic goals were achieved with volume expansion alone; all nine patients survived to leave the hospital. Fifty patients were randomly assigned to the treatment group, and 50 to the control group. During treatment, there were no differences between the two groups in mean arterial pressure or oxygen consumption, despite a significantly higher cardiac index and level of oxygen delivery in the treatment group (P < 0.05). Although the predicted risk of death during hospitalization was 34 percent for both groups, the in-hospital mortality was lower in the control group (34 percent) than in the treatment group (54 percent) (P = 0.04; 95 percent confidence interval, 0.9 to 39.1 percent). CONCLUSIONS: The use of dobutamine to boost the cardiac index and systemic oxygen delivery failed to improve the outcome in this heterogeneous group of critically ill patients. Contrary to what might have been expected, our results suggest that in some cases aggressive efforts to increase oxygen consumption may have been detrimental. PMID- 7993415 TI - Air-abrasive technology: its new role in restorative dentistry. AB - Air-abrasive technology has re-emerged in dentistry. The history, characteristics and clinical applications of this approach are reviewed, including advantages and limitations for the removal of stain, enamel, dentin and decay. Air-abrasive technology may be especially suited for use in bonded restorations. PMID- 7993416 TI - Prescription-event monitoring of 10,401 patients treated with fluvoxamine. AB - Prescription-event monitoring (PEM) is one of two national systems of drug safety monitoring practised in Britain. The objective of this PEM study was to assess the safety of fluvoxamine and to monitor the occurrence of untoward and other events during treatment. A total of 10,401 patients treated with the drug in general practices throughout England were studied and data were analysed in the Drug Safety Research Unit, Southampton. The main outcome measures were the overall incidence of events per 1000 patients; the incidence during the first month of treatment; the mean incidence for months 2-6 of treatment; and the ratio of these rates as a signal that an event could be drug related. The most commonly reported category of events was neuropsychiatric while the most commonly reported individual events were nausea and vomiting. Fluvoxamine was shown to be a safe drug and no unexpected or previously undetected drug-related events were encountered. There was a relatively high incidence of gastro-intestinal symptoms, but other adverse reactions often encountered during treatment with tricyclic antidepressants were not frequently reported. PMID- 7993417 TI - Petrol sniffer's encephalopathy. PMID- 7993418 TI - Psychosocial factors and somatisation in chronic fatigue and allied disorders. PMID- 7993419 TI - ABC of sports medicine. Overuse injury in sport. PMID- 7993420 TI - Definition of the sudden infant death syndrome. PMID- 7993421 TI - Safety of milk from cows treated with bovine somatotropin. PMID- 7993422 TI - The Overseas Doctors Training Scheme: failing expectations. AB - The Overseas Doctors Training Scheme needs appraisal. Set up 10 years ago to improve the quality of postgraduate training that overseas (non-European) doctors receive in Britain, the scheme has been popular, but it is questionable how far it has achieved its aims. If Britain is to continue to employ large numbers of overseas doctors in training grades, both through the scheme and through independent arrangements, the apparent mismatch between their expectations and the reality of what Britain offers must be tackled. PMID- 7993424 TI - Tuberculosis in eastern Europe. PMID- 7993423 TI - Views of elderly patients and their relatives on cardiopulmonary resuscitation. PMID- 7993425 TI - Dialysis-related amyloidosis and acquired renal cystic disease with renal cell carcinoma in uremia. PMID- 7993426 TI - Use of lay personnel. PMID- 7993427 TI - Courteous Linus Pauling. AB - One pity of Linus Pauling's death is that even vitamin C could not keep him living longer. PMID- 7993428 TI - LSD and post-hallucinogen perceptual disorder. PMID- 7993429 TI - Posterior view imaging in pulmonary embolism. PMID- 7993430 TI - Milia during treatment of mycosis fungoides: follicular mycosis fungoides? PMID- 7993431 TI - Re: Secondary reconstruction of abdominal wall defects associated with exstrophy of the bladder. PMID- 7993432 TI - Is human insulin imprinted? PMID- 7993433 TI - Windshield-wiper loosening: a complication of in situ screw fixation of slipped capital femoral epiphysis. PMID- 7993434 TI - To empathize or to dissociate--a physician's dilemma. PMID- 7993435 TI - Computed tomography to evaluate chronic sinusitis. PMID- 7993436 TI - Tests for HIV in lupus. PMID- 7993437 TI - Confidential bedwetting hotline. PMID- 7993438 TI - Surrogate laboratory measures of cyanide intoxication. PMID- 7993439 TI - Does oxytocin release correlate with ECT's efficacy? PMID- 7993440 TI - Should relatives watch resuscitation? May affect doctors' performance. PMID- 7993441 TI - Elderly patients and resuscitation. Nurses' and doctors' views may differ. PMID- 7993442 TI - Resuscitation and patients' views. Discuss implications with the patients. PMID- 7993443 TI - Microscopic haematuria. Prevalence in young men underestimated. PMID- 7993444 TI - Critical airway obstruction. PMID- 7993445 TI - Recent advances in pain relief. PMID- 7993446 TI - 'Persistent' forms and persistence of Chlamydia. PMID- 7993447 TI - Relation of pulse pressure and blood pressure reduction to the incidence of myocardial infarction. PMID- 7993448 TI - Simultaneous chemoradiation: accelerated hypofractionation. PMID- 7993449 TI - Spider bites. PMID- 7993450 TI - Intentional diagnostic sting challenges: an important medical issue. PMID- 7993451 TI - International criteria for neuroblastoma diagnosis, staging, and response to treatment. PMID- 7993452 TI - Fetal heart rate monitoring. PMID- 7993453 TI - Pulmonary artery perforation after Kirschner wire migration: case report and review of literature. PMID- 7993454 TI - Safety of milk from cows treated with bovine somatotrophin. PMID- 7993456 TI - Computer-based diagnostic systems. PMID- 7993457 TI - Glioblastoma treatment. PMID- 7993455 TI - Pregnancy after hormonal correction of severe spermatogenic defect due to mutation in androgen receptor gene. PMID- 7993458 TI - Use of lay personnel. PMID- 7993459 TI - Obesity and difficult intubation. PMID- 7993460 TI - Overseas Doctors Training Scheme. Feedback from past trainees will help. PMID- 7993461 TI - Screening for cystic fibrosis. Screening before pregnancy is preferred. PMID- 7993462 TI - Asthma trends. Causes of wheeze and asthma may differ. PMID- 7993463 TI - Somatostatin in gastroenterology. More studies needed. PMID- 7993464 TI - Overseas Doctors Training Scheme. NHS reforms are causing problems. PMID- 7993465 TI - Definition of the sudden infant death syndrome. Keep current definition. PMID- 7993466 TI - Urinary tract infection in children. Intravenous urography is now superseded for reflux. PMID- 7993467 TI - Managing a Jehovah's Witness who agrees to blood transfusion. PMID- 7993468 TI - Susceptibility of Pseudomonas aeruginosa to anti-pseudomonal antibiotics in a general hospital in Spain from 1989 to 1992. PMID- 7993469 TI - Assay of streptomycin trough concentrations by fluorescence polarization immunoassay. PMID- 7993470 TI - Livedo reticularis and inflammatory carcinoma of the breast. PMID- 7993471 TI - Shared governance. PMID- 7993472 TI - Factors affecting bone mass. PMID- 7993473 TI - Non-pharmacological treatment of hypertension. PMID- 7993474 TI - Enhanced basal nitric oxide production in heart failure. PMID- 7993475 TI - Turks and Kurds. PMID- 7993477 TI - Day-night changes of ambulatory blood pressure in patients with ischaemic cerebrovascular damage. PMID- 7993476 TI - J-P Allain. PMID- 7993478 TI - Transmission of tuberculosis. PMID- 7993479 TI - Association between a deletion polymorphism of the angiotensin-converting-enzyme gene and left ventricular hypertrophy. PMID- 7993480 TI - Science in the courtroom. PMID- 7993481 TI - Temporary dissecting seton for trabeculectomy. PMID- 7993482 TI - On tumor necrosis factor alpha in CF. PMID- 7993483 TI - Handedness: basic physics. AB - In the News & Comment article "Genetic testing set for takeoff" by Rachel Nowak (22 July, p. 464), Michael Liskay of Oregon Health Sciences University in Portland should have been named as the senior scientist on one of the teams that identified MLH1. The test for Charcot-Marie-Tooth disease detects the duplication of the PMP22 gene, not a deletion, as stated in the table accompanying the article (p. 466). PMID- 7993484 TI - Adaptive mutation. PMID- 7993485 TI - Urinary tract isolates in rural Africa. PMID- 7993486 TI - Previous surgery as a contributory cause of abnormalities overlooked on mammograms. PMID- 7993487 TI - Pain control during interventional biliary procedures: epidural vs i.v. sedation. PMID- 7993488 TI - Does cesarean section do it all? PMID- 7993490 TI - Complexity of adjunctive pharmacological agents in ECT. PMID- 7993489 TI - Refractoriness induced by lithium discontinuation despite adequate serum lithium levels. PMID- 7993491 TI - Betel chewing incompletely understood in journal supplement. PMID- 7993492 TI - ACLS training. PMID- 7993493 TI - Autologous transplanted colonic carcinoma in Sprague-Dawley rats. AB - Thirty-five adult male Sprague-Dawley rats received weekly subcutaneous injections of 1,2-dimethylhydrazine (DMH) for 12 weeks. At the end of this period, 31 rats had developed colonic carcinomas (CC). A fragment (1 mm3) of each CC was autotransplanted into the subcapsular space of the left kidney of the respective rats. After an additional 3 weeks, the rats were sacrificed. The left kidney in 20 of the 31 rats (65%) demonstrated tumors at the site of transplantation. The transplanted tumors demonstrated markers of viability such as a PCNA positive cells, mitotic figures, mucin secretion, neo-vascularization, invasion of the adjacent kidney tissue and infiltration of mononuclear cells. The frequency of tumor cells exhibiting the tumor associated antigens CO17-1A, GA73 3, BR55-2, GICA 19-9 was similar or higher in most of the autotransplants when compared to the donor tumor. Since MAb17-1A is being used in immunotherapy of metastatic CC in humans, the present model may offer a feasible method to assess various biotherapeutic approaches of metastatic CC based on the use of MAb17-17A. PMID- 7993494 TI - Euthanasia. Present law protects doctors and patients. PMID- 7993495 TI - Euthanasia. Natural and unnatural death. PMID- 7993496 TI - Sports medicine. Booster doses are not needed. PMID- 7993497 TI - Vulvovaginal candidiasis. PMID- 7993499 TI - Taking away hope. PMID- 7993498 TI - Cervical smear uptake rates. PMID- 7993500 TI - Centuries with amalgam. PMID- 7993501 TI - State-dependent responses of two motor systems in the crayfish, Pacifastacus leniusculus. AB - The expression of both swimmeret and postural motor patterns in crayfish (Pacifastacus leniusculus) were affected by stimulation of a second root of a thoracic ganglion. The response of the swimmeret system depended on the state of the postural system. In most cases, the response of the swimmeret system outlasted the stimulus. Stimulation of a thoracic second root also elicited coordinated responses from the postural system, that outlasted the stimulus. In different preparations, either the flexor excitor motor neurones or the extensor excitor motor neurones were excited by this stimulation. In every case, excitation of one set of motor neurones was accompanied by inhibition of that group's functional antagonists. This stimulation seemed to coordinate the activity of both systems; when stimulation inhibited the flexor motor neurones, then the extensor motor neurones and the swimmeret system were excited. When stimulation excited the flexor motor neurones, then the extensor motor neurones and the swimmeret system were inhibited. Two classes of interneurones that responded to stimulation of a thoracic second root were encountered in the first abdominal ganglion. These interneurones could be the pathway that coordinates the response of the postural and swimmeret systems to stimulation of a thoracic second root. PMID- 7993502 TI - Petrol sniffer's encephalopathy and lead exposure. PMID- 7993503 TI - Preventive health services. PMID- 7993504 TI - Elevation of systemic oxygen delivery in the treatment of critically ill patients. PMID- 7993507 TI - Marked twin-twin transfusion in the absence of nonimmune hydrops. AB - The precise pathophysiology of development of nonimmune hydrops in either the recipient or donor twin associated with twin-twin transfusion syndrome is not entirely clear. At times the recipient twin may develop nonimmune hydrops, but at other times the donor twin, and infrequently both, may develop this ominous complication. We present an unusual cases of this syndrome in which discordant twins, despite neonatal hematocrit levels of 86 and 21% were both nonhydropic and discuss the possible underlying pathophysiology of this occurrence. PMID- 7993506 TI - Does thermal stress decrease uterine blood flow in hypertensive pregnancies? AB - The aim of the study was to determine the acute effects of thermal stress on maternal and fetal circulatory responses in normal and hypertensive patients. Therefore we studied 14 healthy pregnant women and 12 women with compromised pregnancies during short-term heat stress using color Doppler ultrasound in addition to conventional follow-up methods. The uterine vascular resistance increased significantly during the exposure in the high-risk pregnancy group without change in the control group. The results of the present study give strong support to our earlier studies that short-term heat stress seems to be safe in uncomplicated pregnancies but may be detrimental in high-risk pregnancies. PMID- 7993505 TI - Omphalocele in Down syndrome. PMID- 7993508 TI - Mathematical modeling of fetal organ growth using the Rossavik growth model: III. Cardiac ventricle. AB - Growth of the fetal cardiac ventricle has been monitored by total cardiac diameter (TCD), left ventricular systolic (LVSD) and diastolic diameter (LVDD), right ventricular systolic (RVSD) and diastolic diameter (RVDD), left ventricular width (LVW), interventricular septal width (IVSW), and right ventricular width (RVW) from 19 to 39 weeks, menstrual age, in 114 normal Japanese fetuses. Growth curves for these parameters have been determined using a Rossavik growth model [P = c(t)k+s(t)]. R2 values of 89.7, 58.0, 65.3, 77.9, 80.3, 31.1, 30.1, and 26.9 were obtained for TCD, LVSD, LVDD, RVSD, RVDD, LVW, IVSW, and RVW, respectively. Variability analysis indicated a progressive increase in variability with fetal age for these eight parameters. Variability data were used with the growth curve models to determine standard curves for these parameters. These standard curves provide a superior means for evaluating the normal fetal cardiac growth in the fetus and for identifying congenital heart anomalies in utero. PMID- 7993509 TI - Vertical human immunodeficiency virus transmission: a study of placental pathology in relation to maternal risk factors. AB - We examined 48 placentas of human immunodeficiency virus (HIV)-exposed pregnancies morphologically for HIV-specific changes and immunohistologically for the presence of HIV antigen and RNA. Findings were correlated to infectious states of the children and maternal risk factors. Few HIV antigen-positive Hofbauer cells and HIV RNA positive syncytiotrophoblast and Hofbauer cells were detected. HIV-positive cells in the placenta did not correlate with intrauterine infection and maternal immunologic parameters. Light microscopically, we found two changes: immaturity of the terminal villi and allantois vasculopathy. These changes, however, are not HIV specific. Our results show that vertical HIV transmission cannot be diagnosed by morphological examination of the placenta. PMID- 7993510 TI - Fractured clavicle in the neonate: a retrospective three-year review. AB - A hospital-based case-controlled study was undertaken to determine maternal and neonatal characteristics associated with fractured clavicle. A total of 11,604 consecutive vaginal deliveries of liveborn infants in vertex presentation at the Mount Sinai Hospital from 1988 to 1990 were reviewed. Maternal and neonatal characteristics were compared for the neonates with and without a diagnosis of a fractured clavicle. Compared to controls, mothers of neonates with a fractured clavicle were more likely to be nulliparas or primiparas, to have had an operative vaginal delivery, and to have been delivered by an attending as opposed to a resident physician. The fractured clavicle group also had a longer gestational age, greater birthweight, and higher frequency of macrosomic infants. After controlling for maternal parity, type of delivery and infant birthweight, experience of the delivering physician, and gestational age at delivery were not significantly different. Fracture of the clavicle in the neonate is related to maternal parity, mode of delivery, and infant birthweight but not to the level of experience of the delivering physician. PMID- 7993511 TI - Fetal echocardiography in gravidas with historic risk factors for congenital heart disease. AB - All fetal echocardiograms performed at our institution between January 1, 1986, and June 1, 1991, were reviewed. The echocardiogram referral indication and results were verified for all women studied. Historic risk factors under consideration were pregestational diabetes, anticonvulsant or lithium ingestion in the first trimester, and a family history of congenital heart disease. Women with historic risk factors who had either a fetal abnormality on antenatal sonography or a known aneuploid fetus prior to the fetal echocardiograph were excluded. Of the 994 women who had a fetal echocardiogram performed during this study period, 486 (48.9%) were evaluated solely on the basis of a historic risk factor. Four of the 486 women (0.8%) were diagnosed as having a significant fetal structural cardiac malformation. Two of the four fetuses succumbed to obstetric complications. The remaining two infants were delivered at term and are doing well after postnatal cardiac surgery. In this select group of women with risk factors but no recognized fetal abnormality, the incidence of significant cardiac lesions was low. Although indications for fetal echocardiography must be evaluated on an individual basis, our data do not support a recommendation for the routine use of fetal echocardiography as a screening test in all women with historic risk factors. PMID- 7993512 TI - Vaginal and intracervical prostaglandin E2 for cervical ripening: a Doppler study of hemodynamic effects. AB - The hemodynamic effects of vaginally and intracervically administered prostaglandin E2 gel were evaluated by pulsed wave color Doppler ultrasound. Twenty term pregnant mothers were recruited. Mothers were randomized to receive either vaginal or intracervical prostaglandin E2 gel. The hemodynamics was assessed by repeated color Doppler velocimetry of the uterine artery and fetal umbilical and middle cerebral arteries; analysis of variance was used to test statistical significance. In the uterine artery a statistically significant rise (P < or = 0.001) of the pulsatility index (PI) was observed. A slightly higher rise of the PI was observed after intracervical administration, but the difference between the groups was not statistically significant (P = 0.4). The fetal PI remained unchanged both in the umbilical and cerebral vessels throughout the study. The rise in the uterine artery PI is probably caused by an increase in the uterine tone as prostaglandins of the E series usually cause vasodilation. No detectable fetal effects were evident. PMID- 7993513 TI - Congenital complete absence (bilateral agenesis) of the diaphragm: a rare variant of congenital diaphragmatic hernia. AB - Although congenital diaphragmatic hernia is one of the most common congenital anomalies, complete bilateral absence of the diaphragm is a very rare variant, with six cases reported in the literature. A 1040 g black male infant was born at 27 weeks' gestation to a 28-year-old black woman with a history of minimal prenatal care and cocaine abuse during pregnancy. Apgar scores were 2/1/1/0/1 at 1, 5, 10, 15, and 20 minutes, respectively and efforts to resuscitate him were unsuccessful. He died at 2 1/2 hours of age. Autopsy showed complete absence of the diaphragm, pulmonary hypoplasia, and an atrial septal defect of the heart. Cytogenetic studies showed normal male karyotype. We suggest that decreased or interrupted blood supply to the developing diaphragm of this infant may have interrupted normal embryogenesis in the early developmental stages. PMID- 7993514 TI - Fetal liver length measurement does not provide a superior means for prediction of a small for gestational age fetus. AB - To assess the growth of the fetal liver in normal pregnancies and evaluate the ability of fetal liver length measurement for prediction of small for gestational age fetuses, ultrasonographic examinations were performed on 162 normal fetuses, ranging from 15 to 40 weeks menstrual age. The optimal mathematical function and normal range of liver length were generated. The liver length was obtained in 21 small for gestational age fetuses between 34 and 40 weeks, and the ability to use fetal liver length measurement for prediction of small for gestational age fetuses was investigated. A curvilinear relationship was found between the menstrual age and liver length (R2 = 91.9%), and a normal range of liver length measurement for estimating the growth of the fetal liver during normal pregnancy was generated. The liver length was normal in 19 of 21 small for gestational age fetuses (90.5%). The fetal liver length measurement does not provide a superior means for identifying the small for gestational age fetus. PMID- 7993515 TI - Favorable neonatal outcome after fetal entrapment and partially successful Zavanelli maneuver in a case of breech presentation. AB - A 16-year-old primigravida woman presented in advanced labor with a singleton breech presentation. Vaginal delivery was considered to be possible, but entrapment at the level of the fetal thorax occurred. The Zavanelli maneuver was attempted unsuccessfully. A cesarean section was performed immediately but was complicated by lateroflexion of the fetus. The attending pediatrician proceeded to endotracheal intubation and ventilation of the partially born baby. Repositioning of the mother facilitated delivery. The fetus survived without any complications. This case illustrates the lack of scientific data to support decision-making in the case of patients presenting with breech presentation late in labor, as well as the unconventional steps sometimes needed in these situations. PMID- 7993516 TI - Uterine sacculation sonographically mimicking an abdominal pregnancy at 20 weeks' gestation. PMID- 7993517 TI - A technique for intrapartum monitoring of fetuses with congenital bradycardias. AB - Our objective was to construct from readily available components a system that would allow determination of P-wave to P-wave intervals in fetuses with congenital heart block. Using a fetal monitor, bedside patient monitor, spiral electrode, and a special cable described herein, we obtained direct fetal electrocardiograms from two fetuses with autoimmune heart block. Measurement of the atrial rate was made by determining the P-wave to P-wave interval. These determinations were compared to atrial rates measured by M-mode echocardiography in utero and neonatal electrocardiograms. Atrial rates determined by direct fetal electrocardiogram were identical to rates obtained by M-mode echocardiography and within 10 beats/min of rates calculated from neonatal electrocardiograms. Premature ventricular contractions in one fetus were also detected. It is possible to perform continuous and accurate assessments of sinoatrial node activity in fetuses with congenital heart block using components readily available to most obstetricians. PMID- 7993518 TI - Do uterine leiomyomas influence pregnancy outcome? AB - To evaluate the clinical significance of the presence, location, size, and number of uterine leiomyomas in pregnancy, a retrospective cohort study in which pregnancy complications and outcome of pregnant women with uterine myomas was undertaken by routine second trimester ultrasound examination. The case group consisted of 183 consecutive women with uterine myomas detected and followed during the years 1983-1989; the control group was made up of all pregnancies diagnosed and followed at the obstetric clinic during the period 1985-1987. The incidences of preterm delivery (less than 37 weeks), preterm premature rupture of membranes, in utero growth retardation (less than 5th percentile), placental abruptio, placenta previa, postpartum hemorrhage (more than 500 cc), and retained placenta were not significantly increased in the group of women with myomas compared with the general population. However, cesarean sections were more common in women with myomas (23 vs 12%; P < 0.001). Within the group of women with myomas, the incidence of cesarean section was not different in cases with multiple rather than solitary myomas, but it was significantly higher in cases of lower uterine segment compared with fundal myomas (39 vs 18%; P < 0.01) and when the mean diameter of the myoma was greater than 5 cm (35 vs 17%; P = 0.01). Stepwise logistic regression analysis showed that both myoma location and size were independent predictors of the odds of cesarean section. PMID- 7993520 TI - Clerical staff attitudes toward patients in 19 prenatal care clinics in New York City. AB - It is widely believed that prenatal care is essential if women are to have healthy pregnancies and infants. Yet many low income women do not initiate care early in their pregnancies or make sufficient visits for prenatal care. Although financial difficulties are usually considered the main reason why prenatal care is not sought, other barriers have also been identified, such as problems with transportation, child care, and understanding English. A possibly unrecognized barrier to obtaining prenatal care is the frontline clerical staff attitudes toward patients. We surveyed 102 frontline staff in 19 prenatal care clinics serving low-income pregnant women in New York City. We explored staff attitudes toward patients, the benefits patients receive, and staff job satisfaction. The survey revealed that many frontline staff questioned whether patients should receive some prenatal care benefits offered. The staff members felt that their needs were attended to less than those of patients or other health care personnel. The attitudes of frontline staff concerning patients, patient benefits, and perceived lack of recognition at work may influence their interactions with patients and be a factor in patients' satisfaction with prenatal care services. Recognizing and changing factors fostering employee dissatisfaction may improve the "user friendliness" of prenatal care clinics and remove a barrier for low-income women. PMID- 7993519 TI - Risk of eye splash in obstetric procedures. AB - A prospective cross-sectional study was designed to determine the rates of upper facial splash during obstetric deliveries. Macroscopic splashes on the attached eye shields of surgical masks, worn for obstetric deliveries were enumerated for a sample of parturients during a 3-month period. Masks were collected for 68 vaginal and 44 cesarean deliveries, 31% of all deliveries during the study period. For cesarean deliveries, 68% (30) of all masks worn by primary surgeons had at least one splash; 57% (17) of which were heavily contaminated (more than five splashes). For the first assistant, 68% (30) of all masks had at least one splash; 23% (7) of which were heavily contaminated. During vaginal deliveries 44% (30) of masks worn by the delivering physician had at least one splash; 20% (6) of which were heavily contaminated. The primary surgeon in a cesarean section was 1.6 times as likely to be splashed (P < 0.04) when compared with vaginal deliveries and 4.6 times as likely to be heavily contaminated (P < 0.003). Estimated blood loss and the rate of eye splash were linearly related. Method of delivery was not independently associated with eye splash. These findings suggest that the risk of contamination by splash during obstetric procedures is high, particularly for cesarean deliveries because these deliveries tend to have greater blood losses. PMID- 7993521 TI - Resolution of marked intrapartum fetal tachycardia following intravenous nalbuphine hydrochloride. AB - We report a case of a patient who received nalbuphine during labor. The fetus was in an awake state, but when exposed to intravenous nalbuphine manifested quiet sleep. This suggest a physiological response and not a sign of fetal compromise. PMID- 7993522 TI - Blood pressure predicts insulin requirement and exogenous insulin is associated with increased blood pressure in women with gestational diabetes mellitus. AB - Fifty gestational diabetic women were studied to determine the interaction of blood pressure, insulin resistance, and the effect of exogenous insulin on blood pressure response. Gestational diabetes was diagnosed according to the criteria affirmed by the Third International Workshop-Conference on Gestational Diabetes at 20 to 32 weeks' gestation. At diagnosis, all women were placed on a standard diet and performed glucose monitoring on rising and 1 hour after meals. The criteria for initiation of insulin included fasting whole blood finger stick glucose more than 90 mg/dL, ketonuria that could only be cleared by increasing carbohydrate to a level causing postprandial hyperglycemia, or postprandial glucose levels at 1 hour above 140 mg/dL. Of the initial cohort, 28 required insulin to maintain target glycemia. Within this group, there was a significant positive correlation between mean arterial pressures at initiation of therapy for gestational diabetes mellitus and insulin requirement quantified by the amount of insulin required to maintain euglycemia at term (r2 = 0.259; P = 0.006). The initiation of insulin was associated with a significant blood pressure increase in this group when compared with values prior to insulin administration or to values in the group treated with diet alone. These observations are consistent with an interaction of blood pressure and insulin resistance as reflected by insulin requirement in women with gestational diabetes mellitus. PMID- 7993523 TI - Association of isoimmune thrombocytopenia and neonatal hyperinsulinism/hypoglycemia. AB - Neonatal hyperinsulinism and hypoglycemia have a well-established association with maternal Rh isoimmunization. We report herein an infant who presented with significant neonatal hypoglycemia that was found to be secondary to hyperinsulinism and who also had thrombocytopenia secondary to maternal platelet isoimmunization. PMID- 7993524 TI - Viral load and its relationship to quinolinic acid, TNF alpha, and IL-6 levels in the CNS of retroviral infected mice. AB - Mouse models of infection of the central nervous system (CNS) have been used to study retroviral-induced neurologic disease. Ecotropic-neurotropic murine leukemia virus (MuLV) infection of susceptible neonatal mice causes a neurologic disease characterized by progressive hindlimb paralysis. The lesions consist of chronic noninflammatory spongiform change predominantly involving brainstem and spinal cord. Two molecularly cloned strains of MuLV, ts-1, a temperature sensitive mutant of Moloney MuLV, and pNE-8, derived from a feral mouse isolate Cas-Br-E, were used in this study. Infected mice were sacrificed at regular intervals postinoculation throughout the time-course of disease. The neuropathology was evaluated using standard histological and immunohistopathological techniques. Tissue concentrations of viral proteins and potentially cytotoxic factors were compared with the histopathology in select regions of the CNS. Areas of extensive vacuolation with neuronal and oligodendroglial infection were observed in spinal cord, brainstem, and cerebellum. High titers of infectious virus were observed within CNS lesions, whereas low titers were observed in morphologically uninvolved areas. Western blot analysis revealed abundant production of viral envelope proteins, which correlated well with infectious virus titers. Serum quinolinic acid (QUIN) concentrations in both groups of noninfected and infected mice were similar. However, CNS tissue concentrations of QUIN, TNF alpha, and IL-6 in ts-1 infected mice were significantly higher than in pNE-8 infected or noninfected mice. The difference in concentration of these factors may be the result of greater activation of macrophages/microglia in ts-1 infected mice. During murine retroviral encephalitis, CNS damage may be mediated by direct infection of CNS cells and may be enhanced by indirect effects of neurotoxic factors possibly secreted by infected/activated macrophages. PMID- 7993525 TI - Transforming growth factor beta 1 inhibits cytokine-induced CNS endothelial cell activation. AB - Postcapillary endothelium at the sites of inflammation undergoes a series of changes collectively termed endothelial cell activation. Activated endothelium expresses immunologically relevant surface proteins that include MHC class II antigens (Ags) and adhesion proteins, as well as exhibits a number of functional changes. Endothelial activation has not been thoroughly studied in CNS endothelium. We have examined cytokine-mediated endothelial activation in isolated rat CNS microvessels. Freshly isolated rat CNS microvessels are viable in culture for at least 72 h. Untreated microvessels express no endothelial activation antigens, but do exhibit constitutive expression of the transferrin receptor (tfR). INF gamma induces a dose-dependent increase in both MHC class II antigens and tfR measured by immunofluorescent staining and quantitated by laser cytometry. IFN gamma-mediated endothelial cell activation could be inhibited with as little as 2 ng/mL TGF-beta 1. although 100% inhibition was seen with 10 ng/mL TGF-beta 1. Cytokine-preactivated endothelial expression of class II Ag and tfR could also be inhibited by TGF-beta 1. TGF-beta 1-treated microvessels become anergic to IFN gamma stimulation. Results suggest that TGF-beta 1 may have a regulatory role in endothelial activation. PMID- 7993526 TI - High ammonia levels decrease brain acetylcholinesterase activity both in vivo and in vitro. AB - We have tested the effect of ammonium injection on the activity of acetylcholinesterase in rat brain. Fifteen minutes after ip injection of 7 mmol/kg of ammonium acetate, the activity of acetylcholinesterase in brain was reduced significantly. The inhibitory effect varied in a wide range, with a maximum decrease of 60%, and was proportional to the concentration of ammonia reached in the brain. It is also shown that ammonium salts added in vitro to the assay mixture inhibit acetylcholinesterase in brain homogenates competitively. The Ki values for inhibition of the enzyme in vitro were 7.2 and 8.5 mM for ammonium acetate and ammonium chloride, respectively, when acetylcholinesterase was assayed in rat brain homogenates, and 7.6 and 8.3 mM when assayed in mice brain homogenates. These results suggest that at least part of the neurologic effects of ammonia could be mediated by an increase of acetylcholine as a consequence of the inhibition of acetylcholinesterase. PMID- 7993527 TI - Changes in brain and spinal cord water content during recurrent experimental autoimmune encephalomyelitis in female Lewis rats. AB - Regional changes in percent water content, a measure of regional levels of edema, were determined in female Lewis rats during key stages of recurrent experimental autoimmune encephalomyelitis (rEAE). The changes in percent water content of the spinal cord and brainstem closely paralleled the clinical and, to a lesser extent, histological course of rEAE (increasing during exacerbations and decreasing during remissions), whereas the percent water content of the forebrain, thalamus/midbrain, hypothalamus, and cerebellum remained constant and equal to control levels at all stages of the disease process. These results suggest that edema formation and resolution in the brainstem and spinal cord may be significant determinants of the transient and recurrent course of neurological dysfunction exhibited by rats with rEAE. PMID- 7993528 TI - Neuropeptide Y immunoreactive neurons in murine trisomy 16 cortical cultures. Plasticity of expression and differentiation. AB - Neuropeptide Y (NPY)-containing neurons are depleted in the cortices of individuals with Alzheimer disease (AD), yet spared in the striatum of patients with Huntington chorea. It is unknown whether this neuronal phenotype is inherently susceptible to the neurodegenerative processes that are a hallmark of AD. To study this question, the murine trisomy 16 model of Down syndrome and Alzheimer disease was investigated. Since trisomic fetuses die in utero, studies were carried out on primary cultures of dissociated cortical neurons. These were prepared from 15-d gestational trisomy 16 fetuses and their littermate euploid controls, and examined by immunocytochemical staining for neuropeptide Y at 7 and 12 d in vitro. Trisomy 16 neurons were also grown on euploid glial carpets, whereas euploid neurons were grown on trisomic glia. The results demonstrate a significant increase in the number of NPY neurons and a stunting in the dendritic arbor of these neurons in trisomic vs euploid cortex. Both of these parameters could be normalized by direct contact with euploid glia. When euploid cortex was plated on trisomic glia, the number of NPY neurons and their morphology were altered so that they began to resemble trisomic NPY cortical neurons. These results indicate a dysregulation of NPY neuronal expression and differentiation in trisomy 16 cortex that are modifiable by interaction with euploid glia and imply an abnormal trophic (glial) environment in trisomic cortex. PMID- 7993529 TI - U50488 reduces the severity of tissue damage in a rabbit model of focal cerebral ischemia. AB - Many pharmacotherapies for stroke that have been successful in the laboratory have proven to be ineffective in the clinical setting, often because patients do not arrive for treatment until hours after the onset of the ischemic insult. Kappa opioid treatment of cerebral ischemia has been successful in the cat and mouse with treatment delays of up to 6 h. The purpose of the present study was to develop a model of delayed kappa opioid treatment of cerebral ischemia in the rabbit. Fourteen rabbits underwent permanent, unilateral occlusion of the internal carotid, middle cerebral, and anterior cerebral arteries via a transorbital, microsurgical approach. At 6 h postocclusion, animals received a blinded bolus injection and continuous infusion of either saline or the kappa agonist, U50488. Survival was not improved after U50488 treatment. U50488 treatment did, however, reduce areas of severe tissue damage and increase areas of modest tissue damage. This suggests U50488 arrested the progression of damage from noninfarcted to fully infarcted tissue. The present results show beneficial effects of delayed treatment with kappa agonists in a species similar in vasculature to humans, and much less costly than primates or cats. PMID- 7993531 TI - [New records of human diphyllobothriasis in Chile (1981-1992), with a case of multiple Diphyllobothrium latum infection]. AB - Fifteen new human cases of diphyllobothriasis in Chile are reported, one of them a multiple case of infection by Diphyllobothrium latum. Five scolices and 28 m of strobila were recovered after treatment with Niclosamide in a male adult patient with multiple infection. In other 5 cases, after treatment, only one worm was recovered in each person and all corresponded to D. latum species; worms measured between 2.9 to 11.0m. In 9 cases, only the eggs of parasites were reported in the coprological exam. Thirteen cases were determined in the lakes area from south of Chile where infection by plerocercoids in salmonids is very frequent and the persons consume smoked and raw ("cebiche") fishes. PMID- 7993530 TI - [Comparison of the frequency of electrocardiographic changes in groups of apparently healthy persons with a positive serology for Chagas' disease, for toxoplasmosis or for both parasitoses]. AB - In order to compare the frequency of electrocardiographical abnormalities among apparently healthy persons with Trypanosoma cruzi and Toxoplasma gondii infections, electrocardiogram (EKG) and the corresponding indirect hemagglutination tests (IHAT) were performed to 13,444 randomly selected rural and suburban inhabitants from the seven first regions of Chile which are located in the geographic area of distribution of Chagas' disease in the country. The IHAT for each parasitosis resulted positive (titers > or = 1:16) for Chagas' disease alone in 1,289 (9.6%), for toxoplasmosis alone in 3,519 (26.2%) and for the two infections in 994 (7.4%). EKG abnormalities of all type (AAT) and suggestive of a chagasic etiology (ASChE) were found in 18.5 and 8.3% respectively of the T. cruzi infected group, in 10.9 and 3.2% of the T. gondii infected group, in 18.9 and 4.8% of the group simultaneously infected by the two parasites, whereas AAT and ASChE were found in 7.9 and 1.8% of the IHAT negative group. All the corresponding percentage differences between abnormal EKG had a statistical significance (p < 0.05). Besides the increasing of the IHAT positivity, for each infection parallels to the age grouping of the studied persons, a similar situation was observed in the frequence of the AAT and ASChE mainly among people aged > or = 50 years. As T. cruzi and T. gondii infections sometimes isoletely adopt a high virulence and overlap in a proportion higher than 43.0% in Chagas' disease endemic areas, it is advisable to consider these etiologic possibilities in the presence of patients with a myocardiopathy of dubious interpretation, particularly when AIDS is involved. PMID- 7993532 TI - [A modified Strout test, used as a probe for the diagnosis of transplacental Chagas disease. I. Collection and preservation of the newborn's umbilical cord blood]. AB - Two umbilical cord (UC) blood samples are routinarily taken from each newborn (NB) at the University of Chile Maternity Hospital, to determine blood grouping and for detecting syphilis infection respectively. In august-september 1993, an additional UC blood sample was collected from each of 116 NB (with volumes of whole blood ranging 2.7 - 24.5 ml and a mean of 13.5 ml). In order to determine the persistence of the mobility of Trypanosoma cruzi in blood samples stored at three different temperatures (-2 to -4 degrees C, 4 to 6 degrees C and environmental temperature from 16 to 23 degrees C), two experiments were performed: 1) In three centrifuge microtubes mouse blood (C3H strain) abundant T. cruzi trypomastigotes Tulahuen strain were put. 2) In an other similar number of microtubes, with the same concentration of parasites, human serum from UC was added. During the first 12 h in all the samples trypomastigotes with very active mobility were observed. At 72 h mobility persisted in samples with temperature between 4 and 6 degrees C and between 16 and 23 degrees C. Whereas in the samples maintained at -2 to -4 degrees C with parasites in blood plus serum, an important decrease of T. cruzi mobility was observed. The results of this study suggest that UC blood samples could be collected and maintained between 4 and 6 degrees C or at room temperature up to 48 h to be processed by the modified Strout concentration method (MSCM).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7993533 TI - [Indicators for the evaluation of the impact of hydatidosis control programs on the health status of a human population]. AB - The importance of measuring the impact of the hydatidosis control program activities on the health of human populations has been emphasized. The different rates used, as well as their limitations defining new hydatidosis cases, are described. The specific incidence rates for the age group of 0-10 years should be considered, together with the standardization of serologic and echographic screening in young groups, in order to achieve the epidemiological evaluation of the control programs impact on a human population in the short term. PMID- 7993534 TI - [Prevalence of Strongyloides stercoralis infection in childhood. Oran, Salta, Argentina]. AB - An enteroparasitological, clinical and epidemiological study was carried out in 36 infants who attended the Hospital San Vicente de Paul from Oran for medical assistance. The age of the children varied between 0 and 4 years with an average of 28 months. The main clinical causes for consultation were bronchitis (52.8%), inappetence (52.8%) and paleness (27.8%). The general characteristics of the stool samples were: formed 44.4% and diarrheic 55.6%. The frequency of intestinal helminthic and protozoan elements was the following: S. stercoralis 30(83.3%) N. americanus 5(13.9%), A. lumbricoides 7(19.4%), T. trichiura 3(8.3%), H. nana 5(13.9%), G. intestinalis 10(27.8%), I. belli 1 (2.8%) and E. coli 4 (11.1%). The nutritional condition found in the infants, according to the relation high/weight was: eutrophic 17(42.2%), lightly undernourished 9(20.0%), moderately undernourished 9(25.0%) and severely undernourished 1(2.8%). The mean values of hematocrit and hemoglobin found were under those established as minima by the W.H.O. The white blood cells and eosinophils countings were over the normal mean values. PMID- 7993535 TI - [First report of Camallanus corderoi Torres, Teuber and Miranda, 1990 (Nematoda: Camallanidae) in cultured salmonids from Puyehue Lake, Chile]. AB - During 1991, in one of three specimens of Oncorhynchus mykiss cultured in Puyehue Lake (40 degrees 36'S, 72 degrees 26'W) was registered for first time the infection by Camallanus corderoi. Comments on the morphological and geographic distribution of the three species of Camallanus described in South America are also given. PMID- 7993536 TI - [Lepocreadium valdiviensis nov. sp., (Digenea: Lepocreaiidae) parasite of Paralichthys microps Small-eyed flounder in south Chile]. AB - A new species of Lepocreadium, L. valdiviensis (Digenea) from the small intestine of the flounder, Paralicthys microps Gunther, 1881, is described. It differs from the other species of the genus mainly in the distribution of the vitelline follicles, which extends from the posterior extreme of the body to the ventral sucker; anterior portion of the body covered with spines; uterus preovaric; ovary and testes compact. This finding extends the known geographic distribution of the genus and identifies a new host for this taxon. PMID- 7993537 TI - A new record of the parasitic isopod Orbione bonnieri Nobili, 1906 (Crustacea: Isopoda: Epicaridea) from the prawn Palaemon lamarrei in Visakhapatnam Coast, India. AB - Orbione bonnieri is recorded for the first time from India. O. bonnieri is collected from the prawn Palaemon lamarrei as ectoparasite. PMID- 7993538 TI - A new bopyrid isopod Athelges neotenuicaudis (Crustacea: Isopoda: Epicaridea) parasitic on Pagurus kulkarnii from Visakhapatnam Coast, India. AB - A new bopyrid isopod Athelges neotenuicaudis is reported. The new isopod is collected from the crab Pagurus kulkarnii as ectoparasite. They are found in the intertidal region of Mukkam, Visakhapatnam Coast. Andhra Pradesh, India. Athelges neotenuicaudis n. sp. is compared with A. paguri Rathke, 1843; A. tenuicaudis Rathke, 1843; and A. bilobus Rathke. PMID- 7993539 TI - [Frequency of finding helminths eggs in canine stool samples collected in public places in the La Plata city, Argentina]. AB - A study was carried out in order to determine the level of contamination with helminth eggs in different sectors of the city of La Plata, Argentina. A total of 351 fecal pools were collected from streets (328) and parks and public places (23) of this locality. Of these fecal pools, 117 (33.3%) contained eggs of at least one helminth species. The overall frequencies found were: Uncinaria sp. 16.0%, Trichuris vulpis 9.7% and Toxocara canis 10.5%. PMID- 7993540 TI - Effect of dissolution of collagen on adhesion to dentin. AB - A new method of adherend surface treatment was evaluated to determine the effect of adhesion between dentin and adhesive resins. The pretreatment method consisted of the application of 40% phosphoric acid solution to dentin to remove the smear layer and decalcify the superficial dentin layer, followed by 10% sodium hypochlorite to dissolve and remove the exposed dentinal collagen and provide a fresh dentin apatite surface to which adhesive resin is applied. This method features a direct adhesion between the adhesive resin and dentin, with no resin reinforced layer of dentinal collagen and adhesive resin. The adhesive tensile strength after storage in water at 37 degrees C for 24 hours measured 6.7 MPa with the phosphoric acid treatment alone, while the test method produced an initial adhesive strength as high as 9.7 MPa. After 10,000 thermal cycles (4 degrees C to 60 degrees C), the adhesive strength was 6.2 MPa, which was approximately 1.5 times greater than the value obtained with the method using the phosphoric acid solution alone. PMID- 7993541 TI - Denture base reinforcement using woven polyethylene fiber. AB - Reinforcement of acrylic denture base resin with high-performance polyethylene fiber in woven form produced a substantial improvement of stiffness and impact strength, as well as reducing the sensitivity of the material to notches that mimic anatomic features. The mechanical properties of the new systems were not affected by water immersion. Reinforced complete maxillary and mandibular dentures having good appearance and satisfactory fiber/resin integration were achieved using conventional laboratory techniques. These prostheses are undergoing clinical trials with encouraging results. PMID- 7993542 TI - Immersion disinfection of irreversible hydrocolloid impressions with sodium hypochlorite. Part II: Effect on gypsum. AB - This study investigated the effects of various immersion times and concentrations of sodium hypochlorite on irreversible hydrocolloid impressions and resultant gypsum casts. Irreversible hydrocolloid impressions of a test die were immersed for 1, 5, or 10 minutes in water (control), 5.25%, 0.525%, and 0.0525% sodium hypochlorite and then cast in a Type III stone and a Type V stone. Each stone specimen was evaluated for detail reproduction, dimensional change, surface roughness, and surface hardness. The results indicated that impressions may be immersed in sodium hypochlorite for any of the experimental times and concentrations without negative effects on Type V stone casts. However, immersion of impressions in 5.25% sodium hypochlorite causes some surface deterioration on Type III stone casts. PMID- 7993544 TI - Fracture strength of all-ceramic crowns. AB - The fracture strengths of four types of all-ceramic premolar crowns (conventional Vita-Dur, In-Ceram, Dicor, and IPS-Empress) were compared after a preload cycling in aqueous atmosphere. Preload cycling significantly decreased the strength of Vita-Dur crowns. Fracture strength of Vita-Dur crowns was improved when they were luted with either polyalkenoate or adhesive resin cement. The average (standard deviation) of load to fracture of ceramic crowns luted using zinc phosphate cement and after applied preload cycling in distilled water were: Vita Dur, 770 (237) N; Vita In-Ceram, 1060 (341) N; Dicor, 840 (226) N; and IPS-Empress: 891 (185) N. The In-Ceram crowns fractured in two modes: complete fractures at 1276 (207) N; and fractures with the core remaining intact at 808 (292) N. PMID- 7993543 TI - Computer-aided design and transverse strength of screw-retained attachments. AB - Two commercially available, screw-retained attachments and an experimental attachment were modeled and analyzed by computerized finite element method. Mechanical test specimens were then developed. Cast rectangular bars were fabricated with the attachments or were joined by soldering at midspan as a control. These bars were subjected to three-point loading. The soldered connector was stronger than the three attachment designs, and the experimental attachment was stronger than the two commercial products. There was general agreement between the mechanical and finite element testing. The use of computer-aided technology to design dental devices with improved mechanical properties was demonstrated by this study. PMID- 7993545 TI - The creep behavior of denture-supporting tissues and soft lining materials. AB - This study examined the desirable properties of a soft denture liner. The physical behavior of palatal mucosa of young adults was quantified by analyzing creep behavior using Voigt's four-element model. Instantaneous elastic recovery was significantly smaller than instantaneous elastic displacement, and delayed elastic recovery was significantly larger than delayed elastic displacement (P < .05). Viscous recovery was small but detectable. To ascertain whether the characteristics of the mucosa can be replaced with a soft material, a new soft lining material was developed and both behaviors, especially after load release, were compared with each other. It was indicated that by properly controlling the amounts of the crosslinking agent and inorganic filler of the soft material, its properties may be made to approximate those of the mucosa. PMID- 7993546 TI - A comparison of the fit of spark-eroded titanium copings and cast gold alloy copings. AB - The fit of spark-eroded titanium and cast gold alloy copings was compared by assessment of retrieved cement film analogues. This technique was chosen for its simplicity, nondestructive nature, and for the information it provided on overall fit. The present study showed that the overall fit of titanium copings was comparable to that of gold copings. In marginal areas, the space between die and coping was found to be larger for spark-eroded than cast copings. PMID- 7993548 TI - Finishing and polishing of a poly (fluoroalkoxyphosphazene) resilient denture liner. AB - A raised ridge of Novus resilient denture liner was removed from samples using one of three burs, three stones, or a coarse sandpaper disc. Samples were polished using pumice alone, tin oxide alone, or both agents. A flat, unfinished sample served as a control. Average surface roughness of control samples was 0.96 microns. Average surface roughness measurements for reduced samples ranged from 7.21 microns (sandpaper disc) to 3.34 microns (Prolastic wheel). Without polishing, sandpaper discs and serrated burs produced rougher surfaces than stones or the nonserrated bur. The sandpaper disc reduced the liner the quickest. There were no significant differences between treatments or controls after the use of pumice alone or after the use of a combination of pumice and tin oxide. An acceptable finishing protocol for this poly(fluoroalkoxyphosphazene) resilient liner appears to differ from that previously established for a silicone resilient denture liner. PMID- 7993547 TI - Colorimetric evaluation of vita shade resin composites. AB - The shades of several resin composite materials are keyed to the Vita Lumin shade guide. This study was designed to determine whether different composites of the same designated Vita shade were actually similar in color. A small-area colorimeter was used to compare the L*a*b* color parameters of three hybrid resin composites--Pertac-Hybrid, Prisma AP.H, and XRV Herculite. Four Vita shades (A2, B3, C2, and D3) of each material were evaluated. Color differences (delta E values) between composites of the same designated shade ranged from 2.07 for the A2 shades of Herculite and AP.H to 7.64 for the D3 shades of Herculite and Pertac. Color differences in this range are perceptible to many observers under ideal viewing conditions. PMID- 7993549 TI - Changes in mandibular ridge height in relation to aging and length of edentulism period. AB - This study investigated the mandibular height reduction in relationship to aging and the length of edentulism period. Data were collected from 120 edentulous male subjects (complete denture wearers) who were divided into two resorptive age groups. The edentulism period of the subjects was classified as 1 to 5, 5 to 10, and over 10 years. Ridge resorption was estimated on the panoramic radiograph by estimating the original height of the alveolar process as being three times the distance from the inferior border of the mandible to the inferior edge of the mental foramen. According to statistical analysis, the amount of mandibular height reduction increased in the older age group. The mandibular resorption rate was greatest in the earlier stages of edentulism and slowed with longevity of edentulism. PMID- 7993550 TI - Color stability of denture base polymers. AB - One light-polymerized, three heat-polymerized, and three autopolymerized denture base polymers were exposed to coffee, tea, water at 50 degrees C +/- 1 degree C, as well as artificial sunlight and water, and evaluated for color stability. The color characteristics were determined using a computer-controlled spectrophotometer. Water sorption and solubility were assessed, and the materials were also chemically characterized. Coffee and tea stained the denture base materials superficially. Brushing with toothpaste and moderate grinding reduced discoloration to an acceptable level. All materials were relatively color stable when immersed in water at 50 degrees C +/- 1 degree C. The materials behaved differently when exposed to artificial sunlight and water. PMID- 7993551 TI - Proceedings of the Workshop on Methods for Assessing Fluoride Accumulation and Effects in the Body; January 13-15, 1993. PMID- 7993552 TI - Chemical sensors and biosensors for fluoride: current status and developing technologies. AB - Portable sensors for bioanalytes are becoming of increasing interest, because their development will permit analyses of biological samples at the point of sampling, i.e., at the time when an individual is being examined by a health professional. In this paper, the design requirements for a fluoride sensor are outlined. Currently, commercially available fluoride sensors, ion-selective electrodes, do provide the capability to measure fluoride content in samples directly. However, the sensitivity of these devices is lower than the normal content of fluoride in plasma, and thus, samples must be concentrated before measurement. Recent progress in improving the sensitivity of chemical sensors for fluoride shows sensitivities up to 0.1 mumol/L, which is within the range of interest. In addition, the use of biological systems for developing sensors (biosensors) is expanding rapidly, because of the potential of achieving high selectivity and sensitivity through the use of the amplification power of enzymes. However, relatively few enzyme systems have been discovered that are affected by fluoride--thus the need for expanded research to find appropriate enzymes for this purpose. The characteristics of some enzymes, such as adenylate cyclase, that could be used in the development of a fluoride biosensor are discussed. PMID- 7993553 TI - Dental fluorosis: its use as a biomarker. AB - Several epidemiological studies, beginning with those of Dean and co-workers in the 1940's, clearly demonstrate the relationship between dental fluorosis in humans and the level of fluoride in water supplies. These studies and others have shown that, in a population, there is a direct relationship among the degree of enamel fluorosis, plasma and bone fluoride levels, and the concentration of fluoride in drinking water. However, dental fluorosis is a reflection of fluoride exposure only during the time of enamel formation, somewhat limiting its use as a biomarker. In addition, the degree of fluorosis is dependent not only on the total fluoride dose, but also on the timing and duration of fluoride exposure. At the level of an individual response to fluoride exposure, factors such as body weight, activity level, nutritional factors, and the rate of skeletal growth and remodeling are also important. These variables, along with an individual variability in response to similar doses of fluoride, indicate that enamel fluorosis cannot be used as a biological marker of the level of fluoride exposure for an individual. PMID- 7993555 TI - Strategies for improving the assessment of fluoride accumulation in body fluids and tissues. PMID- 7993554 TI - Strategies for improving methods of assessing fluoride accumulation in body fluids and tissues. PMID- 7993556 TI - Strategies for improving the assessment of dental fluorosis. PMID- 7993557 TI - Dental tissue effects of fluoride. AB - It is now well-established that a linear relationship exists between fluoride dose and enamel fluorosis in human populations. With increasing severity, the subsurface enamel all along the tooth becomes increasingly porous (hypomineralized), and the lesion extends toward the inner enamel. In dentin, hypomineralization results in an enhancement of the incremental lines. After eruption, the more severe forms are subject to extensive mechanical breakdown of the surface. The continuum of fluoride-induced changes can best be classified by the TF index, which reflects, on an ordinal scale, the histopathological features and increases in enamel fluoride concentrations. Human and animal studies have shown that it is possible to develop dental fluorosis by exposure during enamel maturation alone. It is less apparent whether an effect of fluoride on the stage of enamel matrix secretion, alone, is able to produce changes in enamel similar to those described as dental fluorosis in man. The clinical concept of post eruptive maturation of erupting sound human enamel, resulting in fluoride uptake, most likely reflects subclinical caries. Incorporation of fluoride into enamel is principally possible only as a result of concomitant enamel dissolution (caries lesion development). At higher fluoride concentrations, calcium-fluoride-like material may form, although the formation, identification, and dissolution of this compound are far from resolved. It is concluded that dental fluorosis is a sensitive way of recording past fluoride exposure because, so far, no other agent or condition in man is known to create changes within the dentition similar to those induced by fluoride. Since the predominant cariostatic effect of fluoride is not due to its uptake by the enamel during tooth development, it is possible to obtain extensive caries reductions without a concomitant risk of dental fluorosis. PMID- 7993558 TI - Non-dental tissue effects of fluoride. AB - The anti-caries effects of water fluoridation are well-established. The non dental tissue effects of fluoride in drinking water, either naturally occurring or as an additive, have been too poorly studied to permit definitive conclusions to be drawn. Claims have been made that fluoride results in an increased occurrence of malignancies, particularly osteogenic sarcoma. Experimental rat data have not resolved this issue, and epidemiologic studies are equally unclear. Initial claims that fluoride offers protection against atherosclerosis remain viable, but here too, much more directed research is needed. Early studies suggested that a water fluoride content greater than 1 ppm resulted in a lower prevalence of osteoporotic fractures. Recent epidemiologic data seriously question this conclusion and raise the possibility that even this relatively low level may increase the prevalence of osteoporotic hip fractures. Other elements, including calcium and magnesium, also vary in amount as water fluoride content varies, and it has proved difficult to distinguish the independent effects of the various nutrients in water from each other. Therapeutic use of fluoride has been largely restricted to studies of its effect on the osteoporotic study, this important issue remains unresolved. This review provides an overview of these issues, focusing on the uncertainties alluded to, and attempting to develop strategies for future research. PMID- 7993559 TI - Epidemiologic indices for measuring the clinical manifestations of dental fluorosis: overview and critique. AB - Several indices have been used to describe the clinical appearance of dental fluorosis. The purpose of this paper is to describe and compare the three principal ones in use today: those developed by Dean (1934, 1942), Thylstrup and Fejerskov (1978), and Horowitz et al. (1984). A recent index (Fluorosis Risk Index) developed by Pendrys (1990) is also included in this review. The continued use of Dean's classification system and derived index (CFI) for more than a half century is testimony to its simplicity and utility. The index has been criticized because the unit of analysis is the person, because criteria are unclear for some categories, or that they lack sensitivity, particularly for severe fluorosis, and because of the way in which data are summarized and reported. The Thylstrup and Fejerskov Index is appealing to clinicians and epidemiologists alike in that it corresponds closely to histological changes that occur in dental fluorosis and to enamel fluoride concentrations, thereby having biological validity. The TSIF described by Horowitz et al. makes a useful contribution because it provides clearer diagnostic criteria and provides for an analysis based on esthetic concerns. The Fluorosis Risk Index appears to be particularly useful for analytical epidemiologic studies, because it is designed to permit a more accurate identification of associations between age-specific exposures to fluoride and the development of dental fluorosis. All three indices in common use today provide useful indices for the study of dental fluorosis. The utility of the Fluorosis Risk Index will be determined as it receives wider use. The selection of one of these indices for use in an epidemiologic study depends in large measure on the purpose of the study. Research needs to continue on the validity of these indices, particularly for mild fluorosis, and on the public's perception of the cosmetic appearance of teeth with different severity levels of fluorosis. PMID- 7993560 TI - Intake and metabolism of fluoride. AB - The purpose of this paper is to discuss the major factors that determine the body burden of inorganic fluoride. Fluoride intake 25 or more years ago was determined mainly by measurement of the concentration of the ion in the drinking water supply. This is not necessarily true today because of ingestion from fluoride containing dental products, the "halo effect", the consumption of bottled water, and the use of water purification systems in the home. Therefore, the concentration of fluoride in drinking water may not be a reliable indicator of previous intake. Under most conditions, fluoride is rapidly and extensively absorbed from the gastrointestinal tract. The rate of gastric absorption is inversely related to the pH of the gastric contents. Overall absorption is reduced by calcium and certain other cations and by elevated plasma fluoride levels. Fluoride removal from plasma occurs by calcified tissue uptake and urinary excretion. About 99% of the body burden of fluoride is associated with calcified tissues, and most of it is not exchangeable. In general, the clearance of fluoride from plasma by the skeleton is inversely related to the stage of skeletal development. Skeletal uptake, however, can be positive or negative, depending on the level of fluoride intake, hormonal status, and other factors. Dentin fluoride concentrations tend to increase throughout life and appear to be similar to those in bone. Research to determine whether dentin is a reliable biomarker for the body burden of fluoride is recommended. The renal clearance of fluoride is high compared with other halogens. It is directly related to urinary pH. Factors that acidify the urine increase the retention of fluoride and vice versa. The renal clearance of fluoride decreases and tissue levels increase when the glomerular filtration rate is depressed on a chronic basis. PMID- 7993561 TI - Current techniques for measuring dental fluorosis: issues in data analysis. AB - The currently popular scoring systems used to diagnosis fluorosis use different measurement units, evaluate variable numbers of sites per person, and involve non comparable groupings of clinical symptoms. Although none of these factors is related to the level of fluoride exposure in the examined population, their combined effect produces fluorosis prevalence values for a population which vary considerably among and within these scoring systems. Intrinsic factors for a scoring system include the inclusion of a questionable category, the minimal level of fluorotic involvement, and the number of affected sites within a subject required for case definition. Thus, a case definition of fluorosis for each scoring system, although not mandatory, would certainly be desirable so that dental epidemiologists and clinical investigators can interpret fluorosis scores relative to risk assessment. On the other hand, ratios of fluorosis prevalence magnitudes, as evidenced by odds ratios, can be more stable between scoring systems when groups with different fluoride exposure levels are compared. There is a strong correlation between extent and specific measures of fluorosis severity for Dean's Index (DI) and the Tooth Surface Index of Fluorosis (TSIF) scoring system, as well as within each scoring system separately. Parallel patterns in fluorosis severity were found among groups with different fluoride exposure on severity levels of fluorosis may be better understood by using relative measures rather than by using differences in severity levels. PMID- 7993562 TI - Strategies for improving the assessment of dental fluorosis: focus on chemical and biochemical aspects. AB - In order to assess fluoride accumulation and effects in developing dental tissues, one must determine the concentration profile of fluoride in the tissue and to assess separately the labile (i.e., free ions in fluid and ions associated with organic matter) and stable (i.e., incorporated into apatite lattice) pools of fluoride. Free fluoride ions in the mineralizing milieu markedly affect the driving force for precipitation and, as a result, the nature of precipitating crystals. The fluoride incorporated into the crystalline lattice increases the stability of the formed mineral. Improvement in the understanding of the mechanism of dental fluorosis requires more comprehensive information about the effects of fluoride on the ionic composition of the fluid phase, the nature of the initially precipitating mineral(s), the interactions between crystals and matrix proteins, and the enzymatic degradation of the proteins. Recent observations relevant to the role of fluoride in enamel formation include: (1) that there are threshold concentrations of fluoride below which the precipitation and hydrolysis of thin-platy octacalcium phosphate is facilitated but beyond which de novo apatite precipitation prevails; (2) that the presence of fluoride in the mineralizing milieu most likely affects the steady-state concentrations of mineral lattice ions; (3) that incorporation of fluoride into the stable pool is retarded by the presence of matrix proteins, particularly amelogenins, which inhibit the growth of apatite crystals; (4) that increasing the degree of fluoridation of apatite crystals enhances the adsorption of amelogenins onto the crystal surface, and (5) that amelogenins pre-adsorbed onto apatite crystals are more resistant to enzymatic cleavages by trypsin (used as a prototype of amelogeninases). PMID- 7993563 TI - Strategies for improving the assessment of dental fluorosis: focus on optical techniques. AB - In its milder forms, enamel fluorosis is characterized clinically by diffuse opacities. The appearance is due to optical properties of a subsurface or surface porous layer with lower mineral content. These areas usually have texture and color similar to those of initial caries lesions but generally another shape and location. Therefore, several optical methods, previously used to diagnose initial caries lesions, were applied to fluoride-induced opacities on extracted premolars and on incisors of four subjects in vivo. These methods included light-scattering measurements, white light illumination, violet light illumination, ultraviolet illumination, and laser fluorescence. Video images were captured with a charge coupled-device (CCD) camera, digitized, and computer-processed. It is concluded that the light-scattering monitor can be used for the determination of the local porosity of fluorotic enamel and that the laser fluorescence method might be developed into a method applicable for the assessment of the severity of enamel fluorosis. PMID- 7993564 TI - Determination of fluorine in biological materials: a review. AB - This review on determination of fluorine in biological materials briefly covers (a) a discussion of various forms of fluorine in body fluids and tissues [and also in foods]; (b) methods of their determination, including pretreatment of samples, separation and concentration of F and its final measurement; (c) an evaluation of the analytical methods used and interpretation of results; and (d) some recommendations for future research in fluorine analytical methods applicable to biological materials. PMID- 7993566 TI - Biological markers: their use in quantitative assessments. AB - Biological markers can be conceptualized in terms of categories of markers that form a continuum representing a sequence of events from exposure to disease. These categories include markers of internal dose, biologically effective dose, early response, and disease. Outside of this sequence are susceptibility factors that can act at any point along the way to modify the effects of external exposures on disease outcomes. Examples of the use of these different types of markers in epidemiologic research are provided. There are many factors that one must consider when selecting a biological marker for use in an epidemiologic study. These factors include: the objectives of the study, the availability and specificity of potential markers, the feasibility of measuring the markers in various biological media, the invasiveness of the techniques necessary to measure the markers, the amount of biological specimen needed for analysis, the time to appearance of the markers in the biological media, the persistence of the markers in biological media, the variability of marker levels within and between individuals, the stability of markers in storage, as well as the cost, sensitivity, specificity, and reliability of the assays used to measure the markers. Each of these characteristics is discussed. The usefulness of biological markers in an epidemiologic study depends on the objectives of the study and whether the properties of the markers fulfill the objectives of the study in a feasible and cost-effective manner. PMID- 7993565 TI - Determination of fluorine in biological materials: reaction paper. AB - Although the fluorine in human tissues may exist in both inorganic and organic (covalently bound) forms, the inorganic fraction is clearly the most relevant for assessing human exposure to, and utilization of, environmental fluoride. There is now general agreement that the inorganic fraction of total tissue fluorine can be accurately determined by a variety of analytical techniques. One of the basic questions considered at this workshop is whether the analysis of a specific tissue or body fluid can provide an estimate of how much of the fluoride to which an individual is exposed actually enters and accumulates in the body. The analysis of hair and nails has been used as an indicator of exposure and utilization for several trace elements, including fluoride. Due to methodological uncertainties regarding sampling and pre-analysis treatment, however, it is presently not possible clearly to distinguish fluoride which is incorporated into hair and nails during formation (endogenous) from that which becomes associated with the tissues following exposure to the environment (exogenous). Consequently, although the fluoride content of hair and nails is clearly increased by environmental exposure to fluoride, the conclusion that these tissues are suitable indicators of fluoride utilization and accumulation in the body is premature. PMID- 7993567 TI - Acute effects of different immunosuppressive drugs on pancreatic, islet, renal, and arterial hepatic blood flow in anesthetized rats. AB - The effects of four different immunosuppressive drugs on organ blood flow were investigated. Sprague-Dawley rats were injected intravenously with 0.2 ml of either 15-deoxyspergualin (DSG; 5 mg/kg body weight), RS 61443 (80 mg/kg body weight), FK 506 (0.5 mg/kg body weight), cyclosporin A (9.5 mg/kg body weight), or the vehicles used. At 15 or 60 min after injection of the drugs, the blood perfusion of the whole pancreas, the pancreatic islets, and the kidneys, as well as the arterial blood flow to the liver, were measured in anesthetized animals using a microsphere technique. Fifteen minutes after administration, both FK 506 and DSG decreased the fraction of whole pancreatic blood flow diverted through the islets. FK 506 and cyclosporin A reduced renal blood flow, but only 60 min after injection of the drug. None of the drugs influenced hepatic blood flow. RS 61443 did not affect the blood flow of the organ systems investigated. These differences in the effects of the drugs tested on blood flow might have some important implications on their efficacy and side effects. Thus, in view of its lack of influence on organ blood flow, RS 61443 seems to be preferable, at least when compared with cyclosporin A and FK 506 in the context of organ transplantation. PMID- 7993569 TI - Effect of small bowel transplantation, denervation and ischaemia on rat intestinal microflora. AB - The effects of denervation and warm ischaemia on quantitative and qualitative changes in small intestinal microflora following rat heterotopic small-bowel isotransplantation were assessed. Animals with Thiry-Vella fistula, but without transplants, acted as controls. Thirty and 40-fold increases in bacterial colony counts were seen in the isografts compared to controls at 2 and 7 days, respectively (P < 0.05). Aerobic faecal organisms predominated at 2 and 7 days, but an overgrowth of Flavobacterium meningosepticum occurred at 28 days in the transplanted and host bowels. The effect of warm ischaemia on intestinal microflora was assessed by the application of a microvascular clamp to the superior mesenteric artery for 90 min. The effect of denervation was assessed following microsurgical division of all nervous tissue around the superior mesenteric artery. After 7 days, lengths of jejunum and ileum were removed and intraluminal microflora assessed. The number of bacterial colonies isolated from the ileum in the warm ischaemia group was six times greater than the number in the control group, whereas no significant changes were seen in the upper bowel. In contrast, denervation led to a slight, but consistent, decrease in colony counts. These findings suggest that the increase in bacterial numbers in an isografted small bowel primarily results from warm ischaemia rather than from mesenteric denervation, and that physical aspects of the procedure may affect the development of sepsis following small-bowel transplantation. PMID- 7993568 TI - Immunohistological studies of complement activation after xenogeneic perfusion of a working heart model. AB - Transplantation of organs from one species to another leads to immediate hyperacute rejection. Activation of complement is one important factor involved in this process. Whether complement activation is induced by preformed natural antibodies (PNAbs) via the classical pathway or by an "activator surface" via the alternative pathway is unclear. In order to simulate the relevant clinical situation of animal donor/human recipient we perfused working porcine hearts ex vivo with human blood. This also offered the possibility to study the process of complement activation in a precisely defined system with human complement proteins. PNAb titer and complement lytic activity of the plasma were measured. Immunohistological stainings for IgG, IgM, C1q, C4, C3d, C5-9, factor B, and properdin were performed on tissue sections of the left ventricle. PNAb titer almost totally disappeared within the first 5 min of perfusion. Complement lytic activity of the classical pathway decreased similarly within the first 3 h of xenogeneic and autologous perfusion from 70% to 40%. More detailed immunohistological studies revealed positive staining for C3d on endothelium and myocardium of ex vivo perfused xenogeneic hearts. Complement-induced cytotoxicity was proven by the presence of C5-9 (membrane attack complex). However, hardly any C1q and C4 could be found in the ex vivo xenogeneic perfused hearts. Staining for factor B was positive and proved activation via the alternative pathway. Beyond that, the presence of properdin binding even indicated an upregulation of the alternative pathway C3 convertase.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7993570 TI - Human papillomavirus type 16 associated with multifocal transitional cell carcinomas of the bladder in two transplanted patients. AB - This report describes two cases of rapidly progressive, multifocal transitional cell carcinomas of the bladder that developed in two patients after renal and cardiac transplantation, respectively. In both cases human papillomavirus (HPV) type 16 DNA was detected using the polymerase chain reaction DNA amplification method. To our knowledge, this HPV type has not been previously described in multifocal bladder transitional cell carcinoma in transplanted patients. Our findings suggest that HPV may play a major role in the development of rapidly progressive, multifocal transitional cell carcinoma in immunosuppressed patients. PMID- 7993571 TI - Genetic requirements for the development of the GVH reaction following small bowel transplantation. AB - The genetic requirements for the development of graft-versus-host (GVH) disease have been investigated in a model of semiallogenic, heterotopic small-bowel transplantation in the rat. Following semiallogenic MHC-incompatible small-bowel transplantation, all graft recipients showed characteristic signs of GVH disease and died within 14 days. On autopsy the transplanted bowel was normal, while the recipient's bowel was dilated and distended with gas. Histology showed a generalized cell infiltration of the connective tissue with macrophages and lymphocytes. After semiallogenic, RT1.A-incompatible, small-bowel transplantation, the graft recipients developed mild and temporary symptoms of GVH disease between days 25 and 40. Only two of the six animals died, while the remaining animals survived the observation period. Small-bowel transplantation across an isolated RT1.C barrier was unable to induce GVH reaction. These results indicate that the development of GVH disease after small-bowel transplantation is controlled genetically by the MHC. Class II MHC incompatibility is necessary for the induction of an acute and lethal GVH reaction. PMID- 7993572 TI - Infiltration patterns of macrophages and lymphocytes in chronically rejecting rat kidney allografts. AB - The migration of circulating leukocytes to sites of inflammation or antigen is based, at least in part, on the activities of adhesion molecules. In the context of organ transplantation, some of these have been shown to be upregulated during acute allograft rejection. As their role during chronic rejection has not been examined, we have used an established rat model to compare sequentially the presence of host cells within the grafts, as defined immunohistologically, with patterns of in vitro leukocyte binding and their dependence upon particular adhesion molecules. Various donor populations of peripheral blood lymphocytes (PBL), lymph node lymphocytes (LNL), and splenic monocytes were interacted with snap-frozen sections of allografted, isografted, and native kidneys at serial intervals up to 24 weeks after transplantation. Monocyte binding in the allografts rose at 8 weeks and peaked at 12 weeks, a period preceding the maximum numbers of macrophages noted immunohistologically in the chronically rejecting grafts at 16 weeks. Lymphocyte binding and infiltration patterns were similar, remaining stable throughout the follow-up period and consistently greater than those noted in isografts. In vitro binding of the monocytes was inhibited by mAbs against ICAM-1, LFA-1, CD18, and MAC-1; MAC-1 did not influence lymphocyte binding, although the other mAbs were effective. We conclude that adhesion molecules are responsible, at least in part, for patterns of cell populations infiltrating chronically rejecting renal allografts. PMID- 7993573 TI - A prospective, double-blind, randomized study of high-versus low-dose OKT3 induction immunosuppression in cadaveric renal transplantation. AB - We undertook a prospective, double-blind study of high-(5-mg) versus low-(2-mg) dose OKT3 for induction immunosuppression (12 days) in cadaveric renal allograft transplantation. Maintenance immunosuppression was identical in both groups and consisted of azathioprine and prednisone initially, with cyclosporine beginning on the 5th postoperative day. Twenty-six patients were randomized. The groups were similar in terms of age, kidney ischemia time, peak PRA, and latest PRA. There were more diabetics and women in the high-dose group. Patient survival at 12 months was 100% in both groups. Graft survival at 12 months was 92% and 100% in the high- and low-dose groups, respectively. Infections were mostly minor and equal in frequency in the two groups. All patients receiving high- or low-dose OKT3 had manifestations of the cytokine release syndrome; these were delayed in onset in the low-dose group. Eleven patients (85%) in each group produced anti OKT3 antibodies. Lymphocyte depletion after 1 day was major (> 98%) and identical in both groups. CD3 antigens were removed more slowly in the low-dose group but eventually at equal rates in both groups. Cost was significantly lower in the low dose group. We conclude that while both doses of OKT3 were effective and safe for induction immunosuppression, it may be prudent to use a lower dose of OKT3 for induction immunosuppression because of its potential to reduce cytokine-mediated effects and to avoid the complications of overimmunosuppression and because of the lower costs associated with it. PMID- 7993574 TI - Risk factors for cytomegalovirus infection and disease in renal transplant recipients: HLA-DR7 and triple therapy. AB - In a prospective study, an analysis of risk factors for the development of cytomegalovirus (CMV) infection and disease was performed on 77 renal allograft recipients. Twenty-five out of the 77 recipients (32%) had a CMV infection. Twenty-two of the recipients received triple immunosuppressive therapy (cyclosporin A, prednisolone, and azathioprine) while the remaining 55 received standard therapy (cyclosporin A and prednisolone). In 23 recipients (30%) acute rejection was diagnosed and the first positive parameter of infection occurred 22 days after rejection therapy. Infection occurred in 10 out of 18 HLA-DR7-positive recipients (56%) and in 15 out of 59 HLA-DR7-negative recipients (25%; P < 0.02). In multiple regression analysis, HLA-DR7 was found to be a significant predictor of CMV infection (P < 0.005). CMV disease was diagnosed in only 9 out of 25 recipients with an acute infection. Six recipients (67%) with CMV disease received triple therapy for maintenance immunosuppression; this was significantly correlated to CMV disease (P < 0.05) as compared to three recipients (33%) with CMV disease maintained with standard therapy. Our data suggest that HLA-DR7 positive recipients are more susceptible to CMV infection and that CMV disease is associated with triple immunosuppressive therapy. PMID- 7993575 TI - Vascular anastomotic techniques for experimental intestinal transplantation. AB - A comparison of two techniques for the vascular anastomosis of intestinal transplants in the rat suggests that the use of an aortic segment with the graft leads to reduced operative time and improved technical success. PMID- 7993576 TI - The use of DNA typing to clarify the origin of metastatic carcinoma after renal transplantation. A clinical and medico-legal problem. AB - We present an unusual diagnostic problem in a transplant patient whose failed renal transplant was found to contain undifferentiated carcinoma. When the patient later developed metastatic renal carcinoma, he began legal proceedings against the hospital for the transmission of a tumour with his renal transplant. He subsequently died of carcinomatosis. Post-mortem examination revealed acquired renal cystic disease in his native kidneys with a 1-cm adenocarcinoma arising from the wall of one of the cysts. We used DNA typing to determine the origin of the metastatic tumour and resolve the medico-legal problem. PMID- 7993577 TI - Abdominal pain that mimics acute appendicitis caused by an ATG overdose in a kidney transplant recipient. PMID- 7993578 TI - Secretion of plasminogen activator inhibitor type 1 by cultured ovarian cells obtained from gonadotropin-treated immature rats. AB - It is demonstrated that i) theca-interstitial compartment synthesizes the majority of plasminogen activator inhibitor type 1 (PAI-1) in the ovary before ovulation, and the follicular wall may therefore serve as a specific barrier with the presence of PAI-1 activity to prevent the secretion of tPA into the extrafollicular compartments; ii) granulosa cells secrete only a small amount of ovarian PAI-1, but synthesize the most of tissue-type plasminogen activator tPA involved in the processes leading to ovulation; iii) since only matured cumulus oocyte complexes secrete a large amount of tPA and PAI-1, both tPA and PAI-1 activity in the conditioned medium may be used as reliable markers for evaluating oocyte quality for in vitro fertilization. PMID- 7993579 TI - Molecular characteristics of four new depressant insect neurotoxins purified from venom of Buthus martensi Karsch by HPLC. AB - Suitable pattern and high yield were obtained when the reverse-phase performance liquid chromatography (RP-HPLC) was used to separate neurotoxins from venom of Chinese scorpion Buthus martensi Karsch. Using this technique, the venom was first separated to two main regions. The toxicity tests show that the insect selective neurotoxical components are concentrated in the latter region, from which five insect-selective neurotoxins designated by BmK IT1-IT5 were obtained. According to the results of the toxicity test as well as the amino acid composition and N-terminal analyses, BmK IT1 is the excitatory insect neurotoxin as reported in a previous paper, and the others are the newly found depressant insect-selective neurotoxins. The molecules of all the four toxins are single chain minipeptides of about 60 amino acids. Their isoelectric points (pI) are between 8.3 and 8.5. The fact that BmK IT2 loses completely its insect toxicity after being modified by fluorochrome shows that the positive charges on the molecular surface of this kind of toxins are important to maintaining the bioactivity of the molecules. PMID- 7993580 TI - Molecular cloning and expression of human interleukin-6 in insect cells. AB - 670-bp hIL-6 cDNA fragments have been amplified by polymerase chain reaction (PCR) using recombinant plasmid pBMIL-6A as templates and two synthetic oligonucleotides containing the optimized translation initiation sequence and restriction sites suitable for cloning as primers. The amplified IL-6 cDNA fragments have then been recombined with a non-fusion expression baculovirus vector pVL1393. The resultant recombinant plasmid pVL. IL-6 together with wtAcMNPV DNAs were transferred into cultured lepidopteran insect cells (Sf9) by calcium phosphate coprecipitation procedure. The recombinant baculoviruses were formed by homologous recombination in vivo between pVL. IL-6 and wtAcMNPV DNAs, screened for plaque assay, and identified by means of dot blotting hybridization. The expressed rhIL-6 was secreted into the culture medium, and its bioactivity was measured through half-maximum H-TdR incorporation into IL-6-dependent cells 7TD1. As a result, the supernatant collected from recombinant baculovirus rAc. IL 6-infected Sf9 cells showed IL-6 activity of 10(6) U/mL. The expression level of rhIL-6 of the supernatant determined by IL-6 ELISA quantitation kit was 1 microgram/mL. PMID- 7993581 TI - Expression of human beta E-globin gene with erythroid enhancer in transgenic mice. AB - The human beta E-globin gene from HbE (beta 26 Glu-->Lys, G-->A) homozygote, a common hemoglobinopathy in China, was injected into the pronuclei of fertilized mouse eggs to prepare transgenic mice. A transgenic mouse bearing 16 copies of construct 5'.HS2 beta E has characteristics of typical transgenic mice. It has been verified that the presence of erythroid enhancer 5'HS2 is necessary for the high level expression of human beta E-globin gene in transgenic mice, indicating that the cis-element 5'HS2 is effective for abnormal beta-globin gene as well. Although the expression level of beta-globin gene was copy number-dependent as reported in previous studies, the average expression level per gene copy (12.1%) in transgenic mice bearing many copies of 5'HS2 beta E (16 copies) was significantly lower than that (79.7%) in transgenic mice bearing fewer copies of the gene (2 copies). The possible mechanisms for this decrease of expression are discussed. Novel hemoglobin tetramers which presumably consist of human beta E globin chains and mouse endogenous alpha-globin chains have been assembled in transgenic mice. PMID- 7993582 TI - Effectiveness of SofScale Calculus Scaling Gel as an aid during dental scaling of teeth of dogs. AB - The effect of pre-scaling application of SofScale Calculus Scaling Gel was studied on teeth of cadaver dogs, comparing scaling time and effort among pre treated and untreated pairs of teeth. Teeth with light, moderate and heavy calculus were studied, treated by either hand-scaling only or hand and ultrasonic scaling. No significant difference was found in overall mean time required, comparing SofScale treated and untreated teeth. Scaling time was faster for SofScale treated teeth with light calculus, and slower for SofScale treated teeth with heavy calculus. There were no differences observed in the effort required for scaling, comparing SofScale treated and untreated teeth. PMID- 7993583 TI - Compliance with oral hygiene recommendations following periodontal treatment in client-owned dogs. AB - A telephone questionnaire survey of owners of 51 dogs was conducted. All 51 dogs had had periodontal treatment at VHUP six months or more previously. At that time, they had received a tooth brush, dentifrice, instructions and a demonstrations of brushing. The owners were asked to brush the dogs' teeth once daily. At the time of survey, 53% of the clients were still brushing several times a week and 38% were no longer brushing at all. PMID- 7993584 TI - Feline lymphoplasmacytic stomatitis associated with monoclonal gammopathy and Bence-Jones proteinuria. AB - Lymphoplasmacytic stomatitis and gingivitis was diagnosed in an 8-year old female domestic shorthair. The cat had evidence of severe generalized inflammation of the oral cavity. Biopsy samples were evaluated and displayed a lichenoid, interface stomatitis which was predominantly lymphoplasmacytic. Serum protein electrophoresis confirmed a monoclonal gammopathy. Urine protein electrophoresis confirmed Bence-Jones proteinuria. Protein electrophoresis was used to diagnose monoclonal gammopathy (the production of a monoclonal immunoglobulin, or paraprotein, which is associated with a characteristic "M" protein spike on serum electrophoresis). Diseases associated with monoclonal gammopathy are similar in the dog and cat. Alkylating agent chemotherapy is used to rapidly reduce paraprotein concentrations in multiple myeloma. Multiple myeloma is the most common disorder associated with monoclonal gammopathy. This condition is less common in the cat, compared to the dog. This report examines the diagnosis and treatment of multiple myeloma in a cat presenting with severe stomatitis. PMID- 7993585 TI - Cybernetic hypothesis of periodontal disease in mammalian carnivores. AB - Factors known to govern the pathogenesis of periodontal disease of carnivores are reinterpreted from an ecological perspective. A cybernetic hypothesis is generated which predicts and explains population control mechanisms. Sensitivity to prevailing conditions and the ability to exert a powerful influence upon those conditions is central to the hypothesis. Natural and domestic situations are contrasted with demonstration of a range of immune-mediated conditions arising from a permanent septic focus in the mouths of domestic cats and dogs. The hypothesis is expected to withstand critical scrutiny. In which case a new theory at the heart of a new paradigm will set the future course. PMID- 7993586 TI - Clinical evaluation of SofScale Calculus Scaling Gel in dogs and cats. AB - An in-depth study was performed using SofScale Calculus Scaling Gel to determine its value in assisting animal dental prophylaxis as compared to nontreated teeth. A total of one hundred and five animals (dogs and cats) were tested. This gel saved a slight amount of time on animal full mouth prophylaxis in many cases, especially in heavy calculus groups. The gel helped to reduce total actual scaling time, but did not reduce actual procedure time. PMID- 7993587 TI - Antigenic relationship between mugwort and ragweed pollens by crossed immunoelectrophoresis. AB - Mugwort and ragweed pollens have been considered as important respiratory allergens in Korea. These two pollens are abundant in the air of Seoul from August through October. Many ragweed-sensitive patients have shown concurrent sensitivities to mugwort pollen. However the antigenic relationship between these two pollens has not been clarified. To observe the cross-reactivity between them, we developed polyclonal anti-mugwort and anti-ragweed antibodies by immunization on New Zealand white rabbits, and performed crossed immunoelectrophoresis(CIE) with two pollen extracts. Five precipitation lines were formed by mugwort and anti-mugwort antibody. One precipitation line was formed by ragweed and anti ragweed antibody. There was no reaction from mugwort and anti-ragweed antibody, and from ragweed and anti-mugwort antibody. These results indicate that there is no cross-antigenicity between mugwort and ragweed pollens. PMID- 7993588 TI - Illness associated with contamination of drinking water supplies with phenol. AB - An accidental spill of phenol (100%) into the Nakdong river with subsequent contamination of the tap water for about two million consumers in Teagu city of Korea occurred in March 1991. A historical cohort study of 6,913 individuals was undertaken to determine association with illness. Population subjects were divided into two groups of exposed and unexposed. Exposed subjects were reported to have significantly more phenol associated symptoms than those in a nearby unexposed area (39.6% vs. 9.4%, p < 0.01). Especially, in the related symptoms, highly significant differences were noted in the number of subjects reporting gastrointestinal illness such as nausea, vomiting, diarrhea, or abdominal pain. During the accident, study subjects who experienced peculiar taste or odor in the tap water were significantly more in the exposed areas (92% vs. 34.3%). PMID- 7993589 TI - EBV in situ hybridization study for non-Hodgkin's lymphomas. AB - Epstein-Barr virus(EBV) has been implicated in the pathogenesis of B lymphoproliferative disorders, T-cell lymphomas and Hodgkin's disease. In this report, we performed an in situ hybridization study on EBV genome in 10 cases of nasal non-Hodgkin's lymphoma(NHL), 20 cases of Waldeyer's ring(WR) NHL, and 20 cases of nodal NHLs to document EBV association with lymphomas in Koreans. For immunophenotyping, monoclonal antibodies for CD 20, MB 2, CD 45Ro & CD 43 were used. For in situ hybridization study, EBV DNA probe for Bam HI 'V' fragment and EBV RNA probe for EBER and BHLF were used. Twenty two cases(44%) of malignant lymphomas were positive for EBV genome. Generally, T-cell lymphomas showed a higher positive rate(61%) than B-cell lymphomas(24%). Among T-cell lymphomas, nasal lymphomas showed a higher positive rate(80%) than WR(50%) or nodal lymphomas(50%). Of 22 EBV genome positive cases, 10 cases were positive for EBER, 10 cases for BHLF, and 2 cases for both EBER and BHLF. The histologic types by Working Formulation(WF) were not correlated with EBV genome positive rate, whereas lymphomas showing the histologic spectrum of polymorphic reticulosis(PR) showed a higher positive rate(65%) than lymphomas without PR-like features(40%). These results indicate that nasal T-cell lymphomas with the histologic spectrum of PR are strongly associated with EBV and that the anatomic site may be an important factor in this association. PMID- 7993590 TI - Splenic lymphoid change in abdominal neoplasmic patients--analysis of 121 cases. AB - Because the spleen is likely to play a specific role in immunity, we have tried to observe the influence of the abdominal neoplasms on splenic lymphoid tissue as well as the distribution and localization of immunoregulatory cells with a special attention to the marginal zone, using splenectomy specimens in the various kinds of 121 abdominal neoplasm patients. As a control group, twenty-six splenectomy specimens from patients with traumatic rupture were used. In splenic size and weight, there was a statistically meaningful increase in the patients with abdominal neoplasms. Among those patients, the evolving activated immune reaction (EVA) was 60.2%, the early activated immune-reaction (EAA) 39.0%, the mixed evolving activated and granulomatous reaction (MIX) 0.8%, unlike EVA 30.8%, EAA 69.2%, and MIX 0% in the normal control group. The reason for this change may be explained by activated lymphoid tissue in the form of EVA type. In conclusion, the splenic lymphoid tissue in the various kinds of abdominal neoplasms, mostly malignant, revealed the chronic immune activated state characterized by the increased number of prominent germinal centers and distinct marginal zones, the latter of which revealed the positive reaction for L26, IgM and IgG, and negative for IgD, as well as showing increased natural killer and dentritic reticulum cells identified by Leu7 and S-100 protein respectively. Therefore, we could at least find the significance of the immunologic role of the spleen in the case of abdominal neoplasms, mostly from malignancy. PMID- 7993591 TI - Schrimer test in Parkinson's disease. AB - We carried out the Schirmer test to measure objectively the amount of lacrimation among 51 clinically diagnosed parkinsonian patients (33 men and 18 women aged 50 to 79 years, mean 64) and 75 age-matched controls (42 men and 33 women aged 50 to 76, mean 62). Whatman No. 2 paper, prepared in precut strips 5mm by 35mm, was placed in the cul-de-sac for five minutes, after which the wetted length of the strip was studied. It was noted that the lacrimation amount decreased in patients with Parkinson's disease compared with controls: the average amount of lacrimation was 3.4 +/- 2.3mm in the former group and 8.1 +/- 6.5mm in the latter group (p < 0.01). We believe that the decrease in the amount of lacrimation is associated with emotional disturbance and autonomic dysfunction, and presume that the lacrimation may be under the control of the basal ganglia which has a connection with the superior salivatory nucleus downward and the limbic system upward. PMID- 7993592 TI - Polyangiitis overlap syndrome: cutaneous leukocytoclastic vasculitis associated with polyarteritis nodosa. AB - A rare case of polyangiitis overlap syndrome is described. The patient was a 25 year-old man who had palpable purpura on his legs which showed leukocytoclastic vasculitis, and polyarteritis nodosa. Superior mesenteric arteriography showed microaneurysms in jejunal branches with focal segmental necrotizing arteritis of small and medium sized muscular arteries in the jejunum. Deposits of IgA and C3 in the superficial blood vessels of the lesional skin were consistent with the features of Henoch-Schonlein purpura. The patient died about two months after initial admission in spite of cytotoxic agent and steroid administration. PMID- 7993593 TI - The prognostic significance of c-erbB-2 and p53 protein expressions in gastric carcinoma--a multivariate analysis of prognostic factors. AB - 152 curative gastrectomy specimens from patients with gastric carcinoma were examined in an attempt to assess the prognostic value of c-erbB-2 and mutant p53 protein expressions. The labeled streptavidin-biotin method was applied to routinely fixed and paraffin-embedded tissue sections, using the polyclonal and monoclonal antibodies against the c-erbB-2 protein and the mutant form p53 protein, respectively. In this examination, staining of c-erbB-2 protein was found in 9.2% of these carcinomas. The c-erbB-2 stained tumors were significantly associated with the tumors whose diameters were smaller than 5cm, and were more likely to be associated with serosal invasion and nodal involvement than the unstained ones. However, there was little association between staining of c-erbB 2 protein and clinicopathologic findings such as age, sex, location, histology, gross type, lymph node status, depth of invasion, and stage. The survival analysis of 104 patients with stage III gastric carcinoma revealed no significant association between c-erbB-2 staining status and survival duration. The 5-year survival rates of the c-erbB-2 positive group and its negative group were 21% and 28%, respectively. Positive p53 protein expression was observed in 46% of 152 carcinomas. There was no significant association between p53 expression and parameters such as age, sex, location, histology, gross type, and size. The p53 stained tumors were more likely to be associated with lymph node metastasis, serosal invasion than p53 unstained ones; but this did not reach significance. The 5-year survival rates of the p53 positive group and counter part group were 27% and 31%, respectively.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7993594 TI - Hepatocellular carcinoma associated hemolytic uremic syndrome unrelated to chemotherapy. AB - A 67-year-old man, diagnosed as hepatocellular carcinoma by percutaneous needle aspiration biopsy of liver mass, presented microangiopathic hemolytic anemia, thrombocytopenia and renal failure from the early phase of the illness. We could establish the diagnosis of cancer-associated hemolytic uremic syndrome which was unrelated to chemotherapy clinically. This is a rare case reported in adult hepatoma patients. PMID- 7993595 TI - Brain abscess from a ganglionic hemorrhage--a case report. AB - We present a unique case of a brain abscess that occurred secondary to a ganglionic hemorrhage in a 64-year-old man. This abscess appeared to be metastatic after septicemia. Aspiration with antibiotics eliminated this infection. PMID- 7993596 TI - A case of extra-hepatic portal hypertension caused by periportal tuberculous lymphadenitis. AB - This report describes a case of portal hypertension caused by periportal tuberculous lymphadenitis. There were a few reports of portal hypertension associated with tuberculosis. A 27-year-old man was admitted to the hospital because of recurrent hematemesis for 7 days. There was a history of mediastinal tuberculous lymphadenitis 3 years earlier that was treated with isoniazide, rifampin, ethambutol, and pyrazinamide for 2 years. Clinical evaluation revealed esophageal variceal bleeding and main portal vein obstruction by enlarged periportal lymph nodes. The patient underwent distal splenorenal shunt. Pathologic examination of the excised periportal lymph node revealed chronic granulomatous inflammation with central caseous necrosis. Thereafter the patient took antituberculous medication for 12 months. The patient has not re-bled 3 years since the shunt operation. PMID- 7993598 TI - Primary localized amyloidosis of the bladder--a case report. AB - Primary localized amyloidosis is a rare disease with an excellent prognosis in most cases. We report a case of primary localized amyloidosis of the bladder that was treated with transurethral resection. PMID- 7993597 TI - A case of primary hyperparathyroidism with hypercalcemic nephropathy in children. AB - Primary hyperparathyroidism is a rare disease in children and is characterized by conspicuous skeletal and renal changes. A 12 year old male patient presented with symptoms of polydipsia, polyuria, general weakness, nausea, and vomiting which had begun 3 months earlier, and showed typical laboratory findings of primary hyperparathyroidism. Confirmatory diagnosis was made by elevated parathyroid hormone concentration in serum, technetium-thallium subtraction scan imaging method and histopathologic finding of chief cell hyperplasia. The laboratory findings revealed elevated levels of BUN, creatinine and decreased GFR. Kidney biopsy showed typical calcium deposits in tubules with marked tubulointerstitial infiltration. After subtotal parathyroidectomy, clinical findings improved remarkably. PMID- 7993599 TI - Pit and fissure sealant application using a drying agent. AB - This clinical investigation assessed the retention of pit and fissure sealants with and without the use of a post-etching drying agent in pediatric dental patients. Twenty eight healthy patients with four fully erupted, non-carious first permanent molars participated. Sixteen males and 12 females, 5-12 years of age, each received four sealants, two with and two without a drying agent. Sealants were placed by three dental operators. Assignment for sealant application (with and without drying agent) was based on a computer-generated randomization table. Sealant application involved cleansing of the teeth with a non-fluoridated prophylaxis paste followed by rinsing 60 seconds with air/water spray, enamel conditioning with 40% phosphoric acid for 60 seconds, rinsing with air/water spray for 60 seconds, application of drying agent for 5 seconds, application of sealant material, and light curing for 60 seconds. Modified USPHS (Ryge) criteria were used to evaluate interfacial staining, secondary caries, marginal integrity, and surface texture. Sealant retention was evaluated as fully retained or lost (failed). All 28 participants returned for the 12-month recall visit. Four evaluators reported a 91% overall retention rate. Of the 56 teeth sealed without a drying agent, there was a 13% (n = 7) failure rate compared to 5% (n = 3) failure rate for the 56 teeth sealed with a drying agent. These results were not statistically significant (P > 0.05) based on the log-rank test. PMID- 7993600 TI - Enamel rehardening with cheese in irradiated patients. AB - Radiotherapy of head and neck malignancies results in severe xerostomia which induces radiation caries. Hard cheese has potent anti-cariogenic effects, even with minimal salivary gland function. Eight patients irradiated for neck cancer volunteered for this study. The saliva flow rate varied between 0.0-0.15 ml/minute. In vitro etched enamel slabs, prepared from human teeth, were exposed intraorally to parafilm stimulated salivary secretion for 5 minutes or, alternatively, to cheese compounds and saliva due to masticating 20 gm hard cheese for 5 minutes. Microhardness measurements were carried out on the enamel surface at start (baseline), after etching and after rehardening. Stimulated saliva or cheese compounds and saliva, due to mastication, induced rehardening of surface enamel in both, non-irradiated and irradiated subjects. The rehardening was significantly increased in the irradiated group consuming cheese as compared to rehardening by stimulated saliva only and not significantly less of that achieved in non-irradiated subjects. Rehardening achieved with stimulated saliva in irradiated patients was of a borderline-significant lower degree in comparison to non-irradiated subjects. The reduced rehardening capacity of a decreased saliva flow in irradiated patients may be complemented by cheese compounds. For xerostomic patients, hard cheese consumption may be regarded as effective to keep initial caries under control. PMID- 7993601 TI - Influence of a dentin bonding agent on the fracture load of Dicor. AB - The purpose of this investigation was to evaluate the effect of a dentin bonding agent on the fracture resistance of a cast glass-ceramic luted to dentin. Sixty beam-shaped Dicor specimens and 40 bovine dentin specimens of similar dimension were prepared and randomly distributed among three groups of 20 each: Dicor specimens (control); Dicor specimens luted to dentin with Dicor Light-Activated Cement; and Dicor specimens luted to dentin with Prisma Universal Bond 3 dentin bonding agent and Dicor Light-Activated Cement. All samples were thermocycled and loaded to flexural failure with an Instron Universal testing machine. The mean fracture loads of the three groups were all statistically different from one another (P < .05). The use of a dentin bonding agent increased the fracture resistance of the resin-cemented glass-ceramic samples by more than three-fold compared to those luted with resin cement alone. The results of this study suggest that the use of a dentin bonding agent in combination with dual-cure resin cement will increase the fracture resistance of castable glass-ceramic restorations. PMID- 7993602 TI - Long term sealing properties of Amalgambond under amalgam restorations. AB - The degree of microleakage at 14 days, 6 months and 1 year between Class V amalgam restorations lined with Copalite varnish or with Amalgambond was compared in this in vitro study. The restored teeth were subjected to cyclic occlusal loading, thermocycling procedures and then stored in a dye solution at the appropriate intervals. Dye penetration was assessed at the gingival and occlusal margins of the restorations. The results showed that with Amalgambond, there was significantly better sealing of the dentin tubules than with Copalite or unlined restorations (P < 0.001) at all times tested. Amalgambond showed significantly less microleakage as compared to unlined restorations (P < 0.01) at all time periods, and significantly less short-term (14 days) microleakage compared with the Copalite-lined group (P < 0.01). PMID- 7993604 TI - Adhesion of a total-etch phosphate ester bonding agent. AB - This study evaluated the shear bond strengths of a phosphate ester bonding agent, Clearfil Photo Bond, using different phosphoric acid gels to etch dentin. The study also tested the shear bond strength of the Clearfil Liner Bond system. Sixty extracted human molars were ground to expose mid-coronal dentin and were randomly assigned to six treatment groups. The first group was left unetched as a control. In the next four groups, dentin was etched with phosphoric acid gels: K etchant (40% with silica thickener); Uni-Etch (polymer-thickened 32%); All-Etch (10%, polymer thickener); or Ultra-Etch (10%, silica thickener). Specimens in the sixth group were etched with 10/20 Ca, a gel with 10% citric acid and 20% calcium chloride. All specimens were bonded with Clearfil Photo Bond and XRV Herculite resin composite. Specimens in the final group also received SA Primer and Protect Liner. After thermocycling, shear bond strengths were determined using an Instron universal testing machine. Mean shear bond strengths ranged from 1.3 MPa (control) to 15.9 MPa (Clearfil Liner Bond). The shear bond strengths of specimens that had been etched with phosphoric acid gels were in the range of 5-8 MPa, and were not significantly affected by either acid concentration or thickener type. SEM examination showed that phosphoric acid demineralized dentin to a depth of 5 microns, while 10/20 Ca demineralized dentin to a depth of only 1 1.5 microns. PMID- 7993605 TI - Base deflection and microleakage of composite restorations. AB - The flexural deflections of human dentin, Herculite XR, Dycal, Vidrion F, zinc phosphate base, and combinations of composite-base were determined. The influence of the flexural deflections in the marginal microleakage was also determined for the composite-base combinations. The flexural deflection test for dentin showed no statistically significant differences between the two floor cavity depths studied. There were significant differences among cements when the thickness of the base was 1 mm whereas no differences occurred at 2 mm. The composite-base combinations did not present statistical differences. There were no statistically significant differences in the microleakage levels among loaded and non-loaded specimens; however, dye penetration was visually greater in loaded samples. PMID- 7993603 TI - Dentin bond strength after air drying and rewetting. AB - The purpose of this study was to investigate the effect of air drying and remoistening of dentin on resin composite bond strength and to determine the extent to which the outermost, collagenous network and surface area of chemically conditioned dentin contributed to interfacial strength. Three components made up the experimental design: The first component comprised 12 experimental groups each containing 10 caries-free molar teeth. Shear bond strength values with dentin were measured for conditioned and non-conditioned dentin to which All-Bond 2 and BisFil were applied. The following values (MPa) were obtained for the groups conditioned with 10% phosphoric acid for 20 seconds: Group 1 (wet control) 24.20 +/- 2.03; Group 2 (10 seconds dried) 19.83 +/- 5.42; Group 3 (30 seconds dried) 11.56 +/- 4.93; Group 4 (10 seconds dried, 5 seconds. remoistened) 25.38 +/- 3.89; Group 5 (30 seconds dried, 5 seconds, remoistened) 24.66 +/- 4.54; Group 6 (5% NaOCl/wet) 25.97 +/- 3.61. For the non-conditioned groups the values were: Group 7 (wet control) 21.54 +/- 4.07; Group 8 (10 seconds dried) 14.62 +/- 3.55; Group 9 (10 seconds dried, 5 seconds remoistened) 16.95 +/- 4.04; Group 10 (5% NaOCl/wet) 13.67 +/- 4.39; Group 11 (air abrasive action) 18.78 +/- 3.62; Group 12 (air abrasive/5% NaOCl) 19.87 +/- 2.03.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7993606 TI - Relationship between degree of polymerization of resin composite and bond strength to Gluma-treated dentin. AB - The purpose of the present study was to investigate the relationship between shear bond strength (SBS) to dentin and degree of polymerization of resin adjacent to the coupling interface. A hybrid-type resin composite was polymerized on Gluma-treated dentin at thicknesses of 1, 2, 3 and 5 mm, respectively, with seven different light activation times (LAT) from 3 through 180 seconds. SBS of the specimens was determined 10 minutes after the end of light activation. The degree of polymerization of resin close to the dentin interface was determined by Wallace Indentation Depth (WID) of specimens polymerized under the same conditions as the SBS samples, however, separated from the dentin surface by a thin glass plate. Consistent relationships were found for SBS vs. LAT and WID vs. LAT by regression analyses (y = A+B/x). There was a strong linear correlation between SBS and WID (r = -0.93), indicating that the early bond strength to Gluma treated dentin is a function of mechanical characteristics of resin close to the bonding interface. PMID- 7993607 TI - Effect of filler content of restorative resins on retentive strength to acid conditioned enamel. AB - In this in vitro study the retentive strength of enamel, either conventionally etched with a phosphoric acid gel or conditioned with an oxalic acid containing etching agent, was investigated. Five experimental restorative resins with filler contents between 0 and 78% by weight were polymerized on the etched enamel surfaces. In spite of the pronounced micromorphological differences of the patterns generated with the two etching agents, the bond strengths mediated were very similar. Application of an intermediate low-viscous or adhesive resin had no influence on bond strength. Exponential relationships were found between the filler content of the resins on the one hand and their flexural moduli and flexural strengths on the other. Significant exponential relations were also demonstrated between filler content and bond strength to the etched enamel surface. The linear relationship between mechanical properties of the resins and their bond strengths to etched enamel indicates that debonding occurred by cohesive failure in resin. PMID- 7993609 TI - Shear bond strength of composite to enamel and dentin using Scotchbond Multi Purpose. AB - A laboratory study was conducted to determine the shear bond strength to enamel and dentin using the Scotchbond Multi-Purpose dental adhesive system. High shear bond strengths of P50 composite to both human enamel (26.8 +/- 5.2 MPa) and bovine enamel (24.8 +/- 4.1 MPa) were found when the system was used according to manufacturer's directions. The mean bond strength for human dentin (25.5 +/- 7.5 MPa) was also similar to that found for bovine dentin (23.4 +/- 4.9 MPa). Variations in the recommended application technique were examined on bovine dentin. Extreme air drying of the primer slightly reduced the mean shear bond strength (19.7 +/- 6.4 MPa), while a significant reduction was observed when the adhesive resin was aggressively air-thinned (10.1 +/- 6.6 Mpa). PMID- 7993610 TI - Quality of life never in the eyes of the beholder! PMID- 7993608 TI - Pooling of long term clinical wear data for posterior composites. AB - Clinical studies to evaluate the wear of posterior composite restorations are complicated by the large number of factors which influence the findings. A multi factorial equation has been developed which successfully normalizes the effects of these factors within studies. This equation is not capable of normalizing these effects for other investigations reported in the literature because study characteristics essential to the analysis are rarely reported. Quantitative estimates of wear rate often differ dramatically between studies and between groups of investigators. The objective of this study was to investigate a potential solution to this problem by ranking materials within studies, using common materials to relate rankings across studies, and achieving an overall pooled ranking for products. An intensive literature search disclosed 78 articles and 46 abstracts on clinical posterior composite wear. All studies were analyzed which involved: (1) more than five restorations per material, (2) Class I or II restorations in posterior adult teeth, (3) characterized commercial products, (4) 2 or 3-year wear data, and (5) information on more than one composite material per study. There were 10 2-year studies involving 25 materials, and 10 3-year studies with 26 materials. Within each study the materials were ranked by wear, and the rankings were converted to centered modified ridits. A meta-analysis combining the data across studies was conducted using ANOVA. Although caution is needed for interpreting significance levels because of the small numbers of products evaluated per study, a high level of agreement in rank correlation of 28 products across qualifying studies was observed.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7993611 TI - Faculty departure from academic programs of physical medicine and rehabilitation. AB - Anecdotal reports suggest that substantial numbers of physiatrists leave academic positions each year, but the specific reasons why departure occurs from academic institutions are opaque. Academic program chairpersons were asked to identify individuals who had left their program in the previous 5 yr, and a confidential survey was sent to those persons. Program chairpersons who responded were from similar programs as chairpersons who did not respond, except they had greater numbers of nonphysiatrists on their faculty. Forty-nine completed surveys were returned. Respondents were generally junior faculty, who had practiced an average of 5.35 yr, and their previous academic position was the first one after residency. The most important reasons for leaving were for a better career opportunity, personal, low job satisfaction with administration and not enough financial reward. The most important changes at the previous institution that might have induced them to stay were fewer administrative/political problems, greater salary, more protected time for academics, effective mentor/role model and more support for research. Statistically significant differences were noted between those who moved to another academic position and those who went into private practice, between those who were in their first job v the second or later job, between program and nonprogram graduates who had long-term expectations and between men and women respondents. Recommendations for faculty retention are discussed. PMID- 7993612 TI - Alteration of immune system function in tetraplegics. A pilot study. AB - Over the past 20 yr, evidence has accumulated that implicates the autonomic nervous system as a central modulator of immune function. We hypothesized that injury to the cervical spinal cord would affect immune function by dysregulation of the sympathetic outflow tract. To test this hypothesis, peripheral blood lymphocytes were obtained from five individuals with complete cervical spinal cord injury (SCI) and from five age- and sex-matched neurologically intact controls. Immunologic parameters studied included cell counts by flow cytometry, lymphocyte proliferation response to three mitogens and a natural killer cell cytotoxicity assay. In addition the Ilfeld Psychiatric Symptom Index was completed by all subjects and controls. Repeated measures analysis of variance revealed an impaired lymphocyte proliferation response in the SCI group. Our results suggest that individuals who have sustained complete cervical SCI have alteration in immune function as compared with neurologically intact controls. This may contribute to infections after spinal cord injury. The mechanism may involve dysregulation of the sympathetic arm of the autonomic nervous system. PMID- 7993613 TI - Lumbosacral radiculopathy screen. Optimizing the number of muscles studies. AB - The literature is unclear as to which muscles and how many are required for a sensitive lumbosacral radiculopathy (LSR) screen. A retrospective study of 247 electrodiagnostically confirmed LSRs in 201 patients over a 3-yr period was conducted to determine how many muscles were required to identify a LSR. All LSRs showed abnormal spontaneous activity (positive waves or fibrillation potentials) in two or more muscles innervated by the same nerve root level but different peripheral nerves. All cases were categorized by radiculopathy level, and the most frequently abnormal individual muscles were combined into different muscle screens. The frequency with which each muscle screen identified a radiculopathy was the frequency with which one or more muscles in the screen displayed abnormal spontaneous activity divided by the total number of radiculopathies. The paraspinal muscles (PM) alone identified 88% of LSRs. Without PM, two muscle screens identified only 14-68%, three muscle screens identified 37-89% and four muscle screens identified 45-92%. Including PM, three muscle screens identified 86-94% of LSRs, four muscle screens identified 91-97% and five muscle screens yielded 94-98% identification. Seven to ten muscle screens resulted in minimal improvements in identifying a LSR with 98-99% identification. We conclude that five muscle LSR screens, including PM, are sufficient to identify LSRs while minimizing patient discomfort and examiner time. PMID- 7993614 TI - Post-traumatic fibromyalgia. A long-term follow-up. AB - This report describes a follow-up study of 176 individuals seen between 1980 and 1990, in whom a diagnosis of post-traumatic fibromyalgia was made. Sixty-seven people completed a lengthy questionnaire and underwent a confirmatory physical examination using the American College of Rheumatology Criteria to confirm or deny the presence of fibromyalgia at the time of follow-up. A total of 60.7% noted the onset of symptoms after a motor vehicle accident, 12.5% after a work injury, 7.1% after surgery, 5.4% after a sports-related injury and 14.3% after other various traumatic events. Fifty-six of 67 individuals had 11 or more tenderpoints (average, 13.5), 3 had 10 tenderpoints, and 7 had fewer than 10 or no tenderpoints. Study subjects were asked to compare the use of the following for the first 2 yr after onset as well as the year preceding the current evaluation: biofeedback, medications, physical therapy, manipulation, massage therapy and tenderpoint injections. In addition, we asked detailed questions regarding symptoms commonly seen in association with fibromyalgia (fatigue, sleep disturbance, etc.). Symptoms of traumatically induced fibromyalgia are quite similar to spontaneous fibromyalgia. There was a dramatic reduction in the use of all forms of physical treatments. Fifty-four percent continued to use over-the counter pain medications, and 39% were on antidepressants. Eighty-five percent of the patients continued to have significant symptoms and clinical evidence of fibromyalgia. PMID- 7993615 TI - Quantitative evaluation of a home exercise program on muscle and functional capacity of patients with osteoarthritis. AB - Rehabilitation of patients with osteoarthritis of the knees is typically based on home exercise. These programs are believed to benefit patients and have been shown to qualitatively improve strength. The purpose of the present study was to quantify the effects of a 3-mo home exercise program on muscle function and functional capacity. The progressive program included flexibility, strength, endurance, active range of motion and functional activities. Nineteen subjects (67.4 +/- 7.5 yr) with osteoarthritis of the knees began the program, with only nine completing it. The subjects initially had significantly reduced muscle function and functional capacity. Maximal isometric strength of knee extension increased significantly at a knee flexion position of 45 degrees for hip flexion positions of 120 degrees and 60 degrees (35%); however, it failed to increase at longer muscle lengths. There were no significant improvements in hamstring strength. Maximal angular velocity improved after 3 mo of exercise (40%). Muscle endurance did not improve significantly. Although there was a slight increase in functional capacity, these data failed to demonstrate significant clinical or statistical improvement in overall function in patients after home exercise. PMID- 7993616 TI - An illustration of clinical gait laboratory use to improve rehabilitation management. AB - The purpose of this report is to illustrate the utility of a gait laboratory as a simple, straightforward aid to psychiatric care. The evaluation and management of a patient with spastic paresis and reduced knee flexion in swing (stiff-legged gait), using quantitative gait analysis, are provided. Spastic quadriceps activity during swing was thought to be the cause of reduced knee flexion, based on traditional physiatric history and physical examination. Gait laboratory analysis, including lower extremity kinematic, kinetic and dynamic electromyographic measurements, demonstrated that the quadriceps were not inappropriately active, as had been expected and suggested, instead, that the reduced knee flexion was secondary to dynamic ankle plantar flexor weakness. Modification of an ankle-foot-orthosis and specific exercises to strengthen the ankle plantar flexors were, therefore, prescribed and resulted in kinematic and kinetic improvements at subsequent gait analysis and a subjective feeling by the patient that gait was better. Gait laboratory analysis was useful in determining the optimal rehabilitation plan. PMID- 7993617 TI - Toward a methodology for rehabilitation research. AB - The field of rehabilitation is becoming increasingly important as the American population ages, seriously ill and injured individuals survive with impairments, and quality of life assumes greater importance in health outcomes assessment. Like other branches of health care, progress in rehabilitation depends on advances in research. However, the rehabilitation process is different from some other facets of health care in that it focuses simultaneously on health outcomes that range from cellular to social. This fundamental difference affects the research methodologies that are appropriate to the field. The strengths and limitations of existing research methods need to be taken into consideration and novel strategies developed to handle the complexity inherent in rehabilitation practice. PMID- 7993618 TI - Ethical issues in physical medicine and rehabilitation. Conclusion to a series. PMID- 7993619 TI - Neuronal transfection in brain slices using particle-mediated gene transfer. AB - Difficulties in neuronal transfection continue to restrict the applicability of molecular approaches to neurobiology. Conventional transfection techniques have been of limited effectiveness, particularly in intact neural tissues. Viral vectors effectively transfect neurons both in vitro and in vivo but are labor intensive to construct, difficult to control, and often compromise cell viability. We describe here an alternative strategy using particle-mediated gene transfer for the transfection of neurons and glia in intact brain slices. This approach is efficient, reliable, and does not require advanced molecular biological facilities for its application. PMID- 7993620 TI - Programmed cell death in Drosophila. PMID- 7993621 TI - Localization of individual calcium channels at the release face of a presynaptic nerve terminal. AB - Studies using biophysical techniques suggest a highly structured organization of calcium channels at the presynaptic transmitter release face (Llinas et al., 1981; Stanley, 1993), but it has not as yet proved possible to localize identified channels at the required nanometer level of resolution. We have used atomic force microscopy on the calyx-type nerve terminal of the chick ciliary ganglion to localize single calcium channels tagged via biotinylated omega conotoxin GVIA to avidin-coated 30 nm gold particles. Calcium channels were in low (modal value approximately < or = 1 per micron 2) and high (modal value approximately 55 per micron 2) density areas and exhibited a prominent interchannel spacing of 40 nm, indicating an intermolecular linkage. Particles were observed in clusters and short linear or parallel linear arrays, groupings that may reflect calcium channel organization at the transmitter release site. PMID- 7993622 TI - Functional properties of multiple synaptotagmins in brain. AB - At least four forms of synaptotagmin are expressed in neurons. Of these, synaptotagmin I has an essential function in mediating Ca(2+)-triggered neurotransmitter release at hippocampal synapses, but the functional implications of multiple synaptotagmins are unknown. Synaptotagmins I-III exhibit a strikingly differential distribution between synapses, with most neurons coexpressing either synaptotagmins I or II with III. Synaptotagmin IV is present uniformly throughout the brain at low levels. Synaptotagmins III and IV are both coexpressed with synaptotagmin I in hippocampal synapses, suggesting that these synaptotagmins are not functionally redundant. The first C2 domains of synaptotagmins I-III exhibit similar Ca2+ affinities in phospholipid-binding assays, whereas that of synaptotagmin IV is unable to bind Ca2+. All synaptotagmins tested bind the clathrin-adaptor protein AP-2 with high affinity. Our results suggest that different synaptotagmins serve distinct but overlapping functions in neuronal membrane traffic, with synaptotagmins I and II representing alternative Ca2+ sensors in exocytosis and all synaptotagmins functioning as AP-2 receptors in endocytosis. PMID- 7993623 TI - Two subcellular mechanisms underlie calcium-dependent facilitation of bioluminescence. AB - Epithelial calcium action potentials in Obelia geniculata trigger brief light flashes from specialized cells by direct activation of cytoplasmic calcium activated photoprotein obelin. During a series of action potentials, sequential flashes undergo characteristic facilitation and decrement with no change in associated spike waveform. Analysis of the subcellular light distribution shows that facilitation results from two processes: recruitment of calcium entry sites and increased light from previously responding localized sites. We propose a model that accounts for the localized flash facilitation and decrement observed in vivo and is based upon the kinetics of calcium binding and emission of obelin. In this model, obelin emits light only when three calcium ions are bound. Changes in flash intensity during successive action potentials result from calcium bound persistently to unexpended obelin, effectively lowering the number of calcium ions required for subsequent activation. Accordingly, facilitation or decrement results from the time-dependent availability of singly and doubly bound obelin. PMID- 7993624 TI - Identification of a syntaxin-binding site on N-type calcium channels. AB - Immunochemical studies have suggested a tight association of syntaxin with N-type calcium channels. Syntaxin specifically interacts with the fusion proteins containing the cytoplasmic loop (LII-III) between homologous repeats II and III of the alpha 1 subunit of the class B N-type calcium channel (alpha 1B) from rat brain, but not with those of the class A Q-type (alpha 1A) or the class S L-type (alpha 1S) calcium channels. This interaction is mediated by an 87 amino acid sequence (773-859) containing two overlapping predicted helix-loop-helix domains. The 87 amino acid peptide can specifically block binding of native N-type calcium channels to syntaxin, indicating that this binding site is required for stable interaction of these two proteins. Interaction takes place with the C-terminal one-third of syntaxin (residues 181-288), which is thought to be anchored in the presynaptic plasma membrane. Our results suggest a direct interaction between the cytoplasmic domains of these two presynaptic membrane proteins that could have an important role in the targeting and docking of synaptic vesicles near N-type calcium channels, enabling tight structural and functional association of calcium entry sites and neurotransmitter release sites. PMID- 7993625 TI - Cloning, expression, and distribution of functionally distinct Ca(2+)-activated K+ channel isoforms from human brain. AB - We have cloned and expressed nine Ca(2+)-activated K+ channel isoforms from human brain. The open reading frames encode proteins ranging from 1154 to 1195 amino acids, and all possess significant identity with the slowpoke gene products in Drosophila and mouse. All isoforms are generated by alternative RNA splicing of a single gene on chromosome 10 at band q22.3 (hslo). RNA splicing occurs at four sites located in the carboxy-terminal portion of the protein and gives rise to at least nine ion channel constructs (hbr1-hbr9). hslo mRNA is expressed abundantly in human brain, and individual isoforms show unique expression patterns. Expression of hslo mRNA in Xenopus oocytes produces robust voltage and Ca(2+) activated K+ currents. Splice variants differ significantly in their Ca2+ sensitivity, suggesting a broad functional role for these channels in the regulation of neuronal excitability. PMID- 7993626 TI - N-glycosylation site tagging suggests a three transmembrane domain topology for the glutamate receptor GluR1. AB - We investigated the transmembrane topology of the glutamate receptor GluR1 by introducing N-glycosylation sites as reporter sites for an extracellular location of the respective site. Our data show that the N-terminus is extracellular, whereas the C-terminus is intracellular. Most importantly, we found only three transmembrane domains (designated TMD A, TMD B, and TMD C), which correspond to the previously proposed TMDs I, III, and IV, respectively. Contrary to earlier models, the putative channel-lining hydrophobic domain TMD II does not span the membrane, but either lies in close proximity to the intracellular face of the plasma membrane or loops into the membrane without transversing it. Furthermore, the region between TMDs III and IV, in previous models believed to be intracellular, is an entirely extracellular domain. PMID- 7993627 TI - Neurotrophins regulate sequential changes in neurotrophin receptor expression by sympathetic neuroblasts. AB - We have examined the mechanisms controlling the induction of the two NGF receptors, trkA and p75, in proliferating neuroblasts immuno-isolated from thoracolumbar embryonic sympathetic ganglia. Contrary to prior studies, we find that induction of p75 follows rather than precedes that of trkA; this late induction is consistent with the fact that p75 functions at relatively late stages of sympathetic development. trkA induction is apparently not controlled by a cell-intrinsic mechanism. Rather, this receptor is induced by environmental signals including NT-3, which also acts as an interim survival factor for these neuroblasts. trkA induction by NT-3 is consequent to its promotion of mitotic arrest, as anti-mitotic drugs also efficiently induce trkA. p75 expression is induced in trkA-expressing cells by NGF. Thus, the development of sympathetic neurons involves sequential actions of different neurotrophins, which also regulate the expression of their own and each other's receptors. PMID- 7993628 TI - Concomitant alterations of physiological and developmental plasticity in Drosophila CaM kinase II-inhibited synapses. AB - Ca2+/calmodulin-dependent protein kinase II (CaM kinase) has been implicated in neural plasticity that underlies learning and memory processes. Transformed strains of Drosophila, ala1 and ala2, expressing a specific inhibitor of CaM kinase are known to be impaired in an associative conditioning behavioral paradigm. We found that these transformants had altered short-term plasticity in synaptic transmission along with abnormal nerve terminal sprouting and directionality of outgrowth. These results represent an interesting parallel with the activity-dependent regulation of synaptic physiology and morphology by the cAMP cascade in Aplysia and Drosophila. In contrast to the learning mutants dunce and rutabaga, which are defective in the cAMP cascade, inhibition of CaM kinase in ala transformants caused increased sprouting at larval neuromuscular junctions near the nerve entry point, rather than altering the higher order branch segments. In addition, synaptic facilitation and potentiation were altered in a manner different from that observed in the cAMP mutants. Furthermore, synaptic currents in ala transformants were characterized by greater variability, suggesting an important role of CaM kinase in the stability of transmission. PMID- 7993629 TI - Saturation of postsynaptic glutamate receptors after quantal release of transmitter. AB - Miniature excitatory postsynaptic currents (mEPSCs) were elicited from small numbers of release sites after brief microperfusion of Ba2+ and K+ onto proximal dendritic processes of hippocampal neurons in culture. Temporal summation of closely timed mEPSCs deviated significantly from linearity. The number of instances of closely timed mEPSCs that were also closely matched in terms of peak amplitudes was significantly greater than that expected by chance. Amplitude pairing became statistically more significant after prolongation of mEPSC duration and inhibition of glutamate receptor desensitization with cyclothiazide. These results are best explained by postsynaptic receptors that approach saturation after quantal release of transmitter. PMID- 7993630 TI - Structural basis of the different gating kinetics of fetal and adult acetylcholine receptors. AB - Structure-function studies have identified key functional motifs in the acetylcholine receptor, including residues that contribute to the ion channel and to the ligand-binding sites. Little is known, however, about determinants of channel gating kinetics. To identify structural correlates of gating, we examined the structural basis of the fetal-to-adult decrease in channel open time conferred by the presence of the epsilon subunit in place of the gamma subunit. By constructing chimeras composed of segments of the epsilon and gamma subunits, we show that the main determinant of this kinetic change is a 30 residue segment of a predicted amphipathic helix located between transmembrane domains M3 and M4. Further subdividing the amphipathic helix revealed that either multiple residues or its overall conformation confers this regulation of channel kinetics. We also show that L440 and M442, conserved residues within M4 of the gamma subunit, contribute to long duration openings characteristic of the fetal receptor. PMID- 7993632 TI - Kir2.1 inward rectifier K+ channels are regulated independently by protein kinases and ATP hydrolysis. AB - Second messenger regulation of IRK1 (Kir2.1) inward rectifier K+ channels was investigated in giant inside-out patches from Xenopus oocytes. Kir2.1-mediated currents that run down completely within minutes upon excision of the patches could be partly restored by application of Mg-ATP together with > 10 microM free Mg2+ to the cytoplasmic side of the patch. As restoration could not be induced by the ATP analogs AMP-PNP or ATP gamma S, this suggests an ATPase-like mechanism. In addition to ATP, the catalytic subunit of cAMP-dependent protein kinase (PKA) induced an increase in current amplitude, which could, however, only be observed if channels were previously or subsequently stimulated by Mg-ATP and free Mg2+. This indicates that functional activity of Kir2.1 channels requires both phosphorylation by PKA and ATP hydrolysis. Moreover, currents could be down regulated by N-heptyl-5-chloro-1-naphthalenesulfonamide, a specific stimulator of protein kinase C (PKC), suggesting that PKA and PKC mediate inverse effects on Kir2.1 channels. Regulation of Kir2.1 channels described here may be an important mechanism for regulation of excitability. PMID- 7993631 TI - Elimination of rapid potassium channel inactivation by phosphorylation of the inactivation gate. AB - The effect of protein kinase C (PKC) on rapid N-type inactivation of K+ channels has not been reported previously. We found that PKC specifically eliminates rapid inactivation of a cloned human A-type K+ channel (hKv3.4), converting this channel from a rapidly inactivating A type to a noninactivating delayed rectifier type. Biochemical analysis showed that the N-terminal domain of hKv3.4 is phosphorylated in vitro by PKC, and mutagenesis experiments revealed that two serines within the inactivation gate at the N-terminus are sites of direct PKC action. Moreover, mutating one of these serines to aspartic acid mimics the action of PKC. Serine phosphorylation may thus prevent rapid inactivation by shielding basic residues known to be critical to the function of the inactivation gate. The regulatory mechanism reported here may have substantial effects on signal coding in the nervous system. PMID- 7993633 TI - Protein kinase C enhances recombinant bovine alpha 1 beta 1 gamma 2L GABAA receptor whole-cell currents expressed in L929 fibroblasts. AB - The beta 1 and gamma 2L subunits of the gamma-aminobutyric acid type A receptor (GABAR) contain phosphorylation sites for PKC. To determine the effect of PKC on GABAR function, whole-cell recordings were obtained from mouse fibroblasts expressing recombinant alpha 1 beta 1 gamma 2L receptors, and catalytically active PKC (PKM) was applied via the recording pipette. The first experiment was a population study. Intracellular application of PKM increased GABAR currents, and the enhancement was antagonized by coapplication of the PKC inhibitory peptide. No acceleration or deceleration of GABAR desensitization was observed. The second experiment was a reimpalement study in which paired recordings were made successively from individual cells. Enhancement of GABAR currents by PKM was again obtained. PKM increased GABAR currents at high (> 10 microM) but not at low (< 10 microM) GABA concentrations, resulting in increases in both EC50 and maximal GABAR current. Thus, PKC phosphorylation enhanced recombinant alpha 1 beta 1 gamma 2L GABAR current by increasing maximal current without increasing the affinity of GABA for the GABARs. PMID- 7993634 TI - The amino terminus of a calcium channel beta subunit sets rates of channel inactivation independently of the subunit's effect on activation. AB - There is molecular diversity in both alpha 1 and beta subunits of voltage-gated Ca2+ channels. Coupling between voltage sensing and pore opening of the C-type alpha 1 (alpha 1c) is improved by the type 2 beta subunit (beta 2), and E-type alpha 1 beta complexes inactivate at different rates depending on the nature of beta. We compared the effects of type 1 and 2 beta subunits on activation of the human E-type alpha 1 (alpha 1E) with the effects they have on inactivation, as seen in Xenopus oocytes. The beta subtypes stimulated activation in similar fashion but affected inactivation differently, and even in opposing directions. beta subunits have a common central core but differ in their N- and C-termini and in a central region. N-terminal chimeras between beta 1 and beta 2 subunits that have opposing effects on inactivation resulted in the reciprocal transfer of their effects. We conclude that regulation of activation and inactivation of alpha 1 by beta are separable events and that the N-terminus of beta is one of the structural determinants important in setting the rate and voltage at which an alpha 1 inactivates. PMID- 7993635 TI - Activation of adenosine A1 and A2 receptors differentially modulates calcium channels and glycinergic synaptic transmission in rat brainstem. AB - Multiple types of calcium channels are responsible for calcium influx that triggers transmitter release in the mammalian CNS. To test the contribution of each calcium channel type on synaptic modulation, we recorded calcium currents from somata of presynaptic interneurons and unitary glycinergic postsynaptic currents in the rat brainstem. In interneuron somata, A1 receptor activation inhibited predominantly N-type (omega-conotoxin GVIA-sensitive) and, to a lesser extent, P-type (omega-agatoxin IVA-sensitive) channels. At the presynaptic terminal, N- and P-type channels mediated synaptic transmission. omega-CgTx occluded synaptic inhibition by A1 receptor activation, suggesting that synaptic inhibition was mediated predominantly by N-type channel inhibition. A2 receptor activation facilitated synaptic transmission, probably through potentiation of P type channels at the presynaptic terminal. PMID- 7993636 TI - Depolarization-induced suppression of GABAergic inhibition in rat hippocampal pyramidal cells: G protein involvement in a presynaptic mechanism. AB - Following postsynaptic activation of a pyramidal cell, the degree of GABAergic synaptic inhibition that the cell receives is reduced dramatically for many seconds. Previously, we found that induction of depolarization-induced suppression of inhibition (DSI) required post-synaptic increases in intracellular [Ca2+], but absence of a decrease in responsiveness to iontophoretically applied GABA left the mechanism of DSI expression uncertain. We investigated DSI with whole-cell voltage-clamp recordings in rat hippocampal slices. Bath-applied carbachol was ordinarily used to increase the spontaneous action potential induced IPSCs (sIPSCs) and enhance detectability of DSI; synaptically released ACh has the same effects. TTX-sensitive sIPSCs are markedly reduced by DSI, whereas TTX-insensitive miniature IPSC amplitudes do not change, suggesting that DSI represents a retrograde influence on presynaptic GABA release. A lag (approximately 1 s) prior to maximal DSI and prevention of DSI by pertussis toxin pointed to a G protein-linked second messenger that may be presynaptic, since perturbation of postsynaptic G protein function did not alter DSI. PMID- 7993637 TI - Heterodimerization between mineralocorticoid and glucocorticoid receptor: a new principle of glucocorticoid action in the CNS. AB - In the mammalian central nervous system, responsiveness to glucocorticoids is mediated by both the mineralocorticoid receptor (MR) and the glucocorticoid receptor (GR). These pharmacologically distinct receptors are believed to bind to common response elements as homodimers. We provide evidence that MR and GR can form a heterodimeric complex with DNA-binding and transactivation properties different from those of the respective homodimers. There was a high degree of cooperativity of MR and GR in binding to a glucocorticoid response element. Transient transfection of a neuroblastoma cell line revealed a transcriptional response pattern of coexpressed MR and GR distinct from that obtained by MR or GR alone. Our findings demonstrate that heterodimerization of MR and GR is a hitherto unrecognized principle for the transcriptional regulation of glucocorticoid-responsive genes in tissue coexpressing these receptors. PMID- 7993638 TI - Microtubules are involved in the localization of tau mRNA in primary neuronal cell cultures. AB - Subcellular localization of neuronal mRNAs contributes to the development of identifiable microdomains. In differentiated neurons, tau mRNA is localized in the cell body and the proximal portion of the axon, and MAP2 mRNA is localized in the cell body and dendrites, whereas tubulin mRNA is restricted to the cell body. To investigate the mechanism(s) leading to segregation of mictrotubule-associated protein mRNA, we examined the role of the cytoskeleton in this process. Detergent extraction of primary neuronal cells in culture followed by in situ hybridization analysis demonstrated that tau mRNA remains bound to cytoskeleton of the treated cells. In addition, biochemical fractionation showed that tau and MAP2 mRNAs are preferentially associated with the fraction of assembled microtubules. In contrast, mRNAs restricted to the neuronal cell body, such as those of tubulin, the 68 kDa neurofilament, and mouse GAPDH, are preferentially found in the supernatant. Using cytoskeletal inhibitors, we demonstrate that tau mRNA is associated with the microtubule system, and not with the actin filaments, thus supporting the hypothesis that the mechanism of mRNA localization is a multistep pathway in which the microtubules play a crucial role. PMID- 7993640 TI - A population-based survey of ovarian malignancies in the southeast health care region of Sweden 1984-1987. AB - All 426 patients with ovarian malignancies registered in the population-based Tumor Registry of the Southeast region of Sweden during 1984 to 1987 were analyzed by survey of the hospital records and population registry data. After comparison with other population-based materials, it seems that the overall survival figures have improved in ovarian cancer. Excluding patients diagnosed at autopsy a 5-year corrected survival of 43% was recorded. Among patients aged under 45 years the corrected 5-year survival was 72%. In a Cox's regression analysis age and stage were significant predictors of cancer death while histology (epithelial vs. non-epithelial), although significant in the univariate analysis, did not add prognostic information in the multivariate model. The relative cancer death rate was 6.4 for patients aged over 74 years compared with those aged under 45 (p < 0.0001), and 13.8 for FIGO stage IV compared to stage I (p < 0.0001). For patients with advanced stage tumors (FIGO stage III or IV) postoperative residual tumor, stage, and age were independent prognostic factors in a multivariate analysis. The corrected cancer death rate was 2.0 for patients with > 1 cm relative to < or = 1 cm postoperative residual tumor nodule(s) (p < 0.0001). PMID- 7993639 TI - Magnus Strandqvist: 50th anniversary of his doctoral thesis. AB - This article is dedicated to Magnus Strandqvist's famous doctoral thesis "Studien uber die kumulative Wirkung der Rontgenstrahlen bei Fraktionierung. Erfahrungen aus dem Radiumhemmet an 280 Haut- und Lippenkarzinomen" published in Acta Radiologica in 1944. After a short biography of Strandqvist some central points of his work and their influence on future development of modern radiotherapy are presented. PMID- 7993641 TI - TAG-72, CA 19.9 and CEA as tumor markers in gastric cancer. AB - Serum levels of CEA, CA 19.9 and TAG-72 were measured in 79 patients with active gastric cancer, 47 with treated gastric cancer and no clinical evidence of the disease and 33 with benign gastric disease. In the patients with active gastric cancer TAG-72 was increased in 47%, CA 19.9 in 46% and CEA in 33%. The sensitivity of these markers was related to the stage of the disease, although upon comparison of stages I-II and III-IV significant difference was observed only for TAG-72. The combined use of two of the markers increased the sensitivity compared with the use of only one. The results suggest that the combination of TAG-72 and CA 19.9 may be useful in the post surgical management of patients with gastric cancer. PMID- 7993642 TI - Management of early breast cancer in southeast Netherlands since 1984. A population-based study. Regional Breast Cancer Study Group. AB - We studied changes in staging and treatment of patients with early breast cancer (TNM stage I and II) in eight community hospitals in southeast Netherlands between 1984 and 1991 and related these changes to the guidelines for the management of breast cancer drawn up by the regional Breast Cancer Study Group. Since 1984, the proportion of patients that underwent breast-conserving therapy (local tumour excision, axillary dissection, and irradiation of the breast) increased from 26% to 53%. Although the mean number of axillary lymph nodes examined by the pathologists increased significantly, the proportion of patients with positive lymph nodes remained unchanged. The proportion of patients with involved axillary nodes receiving any form of adjuvant systemic therapy increased from 49% to 82%. Therapeutic policy initially varied significantly from one hospital to another but gradually became more uniform. We conclude that, except for elderly patients, treatment of early breast cancer corresponded increasingly to the guidelines of the regional Breast Cancer Study Group. PMID- 7993643 TI - Classical prognostic factors for survival and loco-regional control in breast cancer patients treated with radical mastectomy alone. AB - A retrospective analysis of clinical and pathological prognostic factors was performed in 1,068 breast cancer patients treated with radical mastectomy alone in 1952-1980. Three endpoints were considered: 10-year survival, 10-year disease free survival and 10-year loco-regional relapse-free survival. Both univariate and multivariate analyses confirmed the prognostic significance of tumour size, histological type and grade (Bloom classification) and involvement of axillary nodes for all three endpoints. Additionally, young age appeared to be a significant risk factor for loco-regional disease-free survival. Prognostic subgroups were defined by the use of 3 main indicators. In node negative patients with T1 tumours the prognosis seemed to be good regardless of histological grade (80-90% 10-year disease-free survival), in T2 tumours the survival was significantly dependent on histological type and grade. In node positive patients increasing number of involved nodes and higher histological grade had an independent adverse effect on all three endpoints. The study demonstrates that classical, commonly available prognostic factors clearly distinguish subgroups with different prognosis, which may be helpful when deciding on the use of adjuvant local and/or systemic therapies. PMID- 7993644 TI - Male breast cancer. Report of a series of 50 cases. AB - Fifty consecutive cases of male breast cancer (MBC) treated in a single institution were studied. Presentation of the disease, histology, pattern of relapse, and major prognostic factors were similar to those known in female breast cancer (FBC). Five-year disease-free interval and survival were 59% and 75% respectively. Endocrine therapy for treatment of metastatic MBC was proven to be effective with a response rate of about 50% of patients, unselected with regard to oestrogen receptors. A group of patients receiving adjuvant treatment showed lower recurrence rate and a trend toward better outcome than similar stage patients without adjuvant treatment. The present study combined with the recent literature suggests that MBC and FBC are biologically comparable and that inference from experience in treatment of FBC may be justified. PMID- 7993645 TI - Expression of the multidrug-resistance gene product in untreated human breast cancer and its relationship to prognostic markers. AB - The immunohistochemical expression of the 170-kDa permeability glycoprotein (P gp) was investigated in 41 primary untreated breast carcinomas, using the monoclonal antibodies C219 and MRK16. DNA ploidy by flow cytometry and estrogen (ER) and progesterone receptor (PgR) contents were also determined. P-gp expression, as revealed by C219 or MRK16, was observed in 6 (14%) of the investigated cancers. P-gp expression had a tendency to occur in non-diploid, high-grade tumors as well as in patients with lymph node negative disease. However, except for lymph node status, these associations were not statistically significant. No positive statistical relationships were observed between other prognostic parameters (age, tumor size, and receptor status) and P-gp expression. Considering the great heterogeneity observed in previous studies and the low expression of P-gp observed hereby, the utility of P-gp immunostaining as a guide for therapy planning in patients with breast cancer remains uncertain. PMID- 7993646 TI - Clinical studies of liposome-encapsulated doxorubicin. AB - Initial clinical studies with doxorubicin entrapped in the bilayer of phosphatidylglycerol-rich liposomes were hindered by the avid reticuloendothelial system (RES) uptake and by drug leakage from circulating liposomes. In contrast, recent tests of a doxorubicin formulation of polyethyleneglycol-coated liposomes (Doxil) in cancer patients indicate that the drug pharmacokinetic properties are significantly altered, with a prolonged distribution half-life of approximately 2 days. Plasma fractionation studies show that nearly all the drug measured in plasma is in liposome-encapsulated form. The dose of Doxil has been escalated from 25 to 60 mg/m2. Stomatitis is the most significant toxicity, and skin toxicity, in the form of hand-foot syndrome, may complicate the repeated administration of Doxil. A number of objective antitumor responses in a variety of malignancies have been observed, indicating that Doxil is an active antitumor compound. Polyethyleneglycol-coated liposomes show a distinct advantage over previous liposome formulations directed at the RES and appear to be a promising drug delivery system for doxorubicin. PMID- 7993647 TI - Reversal of multidrug resistance by new dihydropyridines with low calcium antagonist activity. AB - The clinical use of Ca++ antagonist agents as modulators of multidrug resistance is limited by their strong vasodilator activity. This study reports data obtained by testing a series of new 1,4 dihydropyridine derivatives (DHPs) for their in vitro resistance modulating activity and their Ca++ antagonist effect. All the tested DHPs are active to increase doxorubicin activity with dose modifying factor values ranging between 2 and 47 on P388/DX cells and 12 and 36 on LoVo/DX cells. Their resistance modulating action is exerted through an increase of DX intracellular level. The Ca++ antagonist activity of DHPs, evaluated as capacity to inhibit the KCl-induced contractions in isolated Guinea pig ileum strips, is not related to their resistance modulating activity. This finding makes it possible to select, for further in vivo evaluations, compounds IX, X and XI, which have strong ability to overcome multidrug resistance and low Ca++ antagonist effect. PMID- 7993648 TI - Effects of a modified CMF treatment (cyclophosphamide, methotrexate and 5 fluorouracil) on hematopoietic tissues and Yoshida sarcoma in rats. AB - Effects of a modified CMF treatment on hematopoietic tissue and an implanted tumor were studied in rats. The modification of the treatment refers to the application of cyclophosphamide 24 h after methotrexate and 5-fluorouracil. The study was done on Wistar rats bearing Yoshida sarcoma in the ascites form. The controls were a) untreated animals bearing the tumor or b) treated conventionally with the 3 cytostatics and c) tumor-free animals under either conventional treatment or d) modified treatment. We examined survival, the appearance of metastases, and the regeneration of hematopoietic tissues. Improved survival, the absence of metastases, and improved regeneration of hematopoietic tissues was observed when modified CMF treatment was applied. These results support the importance of sequencing cytostatic protocols for basic hematological determinants and anti-tumor activity. PMID- 7993649 TI - Drug-sensitivity and DNA-binding of a subform of topoisomerase II alpha in resistant human HL-60 cells. AB - Topoisomerase II alpha (170 kDa) expressed in human HL-60 cells is heterogeneous in charge. By two-dimensional electrophoresis and chromatofocussing two major subforms with pI of 6.5 and 6.7 can be resolved. By preparative anion-exchange chromatography we separated the known topoisomerase II isoenzymes (170/180 kDa) and in addition a late-eluting 170 kDa form, which has not been described before. The catalytic optimum of this late-eluting form is shifted to pH 9.4. It is more than 100-fold resistant to orthovanadate, amsacrine or etoposide, and has an increased salt stability. SDS-treatment induces covalent attachment of this enzyme fraction to calf thymus DNA in the absence of drug. The latter observations indicate an increase in DNA-binding. In the tightly DNA-bound state the late-eluting enzyme is not targeted by cleavable complex forming drugs. Accordingly, cells may become drug-resistant by expressing this form predominantly. PMID- 7993650 TI - Carbogen breathing in patients with glioblastoma multiforme submitted to radiotherapy. Assessment of gas exchange parameters. AB - It has been reported that carbogen breathing yields a remarkable increase of radiosensitivity in murine tumour models. Hence, application of carbogen might be promising in radiotherapy of human tumours. We describe a method to increase arterial oxygenation and to ensure stability of O2 and CO2 during carbogen breathing in patients with malignant disease. We measured in 6 patients with histologically proven intracranial glioblastoma multiforme arterial blood gases, inspired and expired gas concentrations and vital signs either baseline and during carbogen breathing. The highest values of arterial oxygenation were achieved after 10 min of carbogen breathing and they remained stable up to 15 min. In none of our patients was N2 wash-out from the lungs completed in 15 min of carbogen breathing. In conclusion, carbogen breathing increased arterial oxygenation in patients with intracranial malignant diseases. The system used is reliable and of practical use. Monitoring of expired gas concentrations is highly recommended. PMID- 7993651 TI - The response of quiescent cell populations in murine solid tumors to irradiation with fast neutrons. AB - 5-bromo-2'-deoxyuridine (BUdR) was injected into SCC VII tumor-bearing mice intraperitoneally to label all proliferating tumor cells. The mice were irradiated with fast neutrons or x-rays. Immediately, or 24 h after irradiation, the tumors were excised, minced and trypsinized. The tumor cell suspensions were incubated with cytochalasin-B (a cytokinesis blocker). The micronucleus frequency was determined using immunofluorescence staining to BUdR. The cells that were not labeled with BUdR could be regarded as the quiescent cells. The micronucleus frequency in total tumor cells was determined from the irradiated tumors that were not pretreated with BUdR. The difference in radiosensitivity between total and quiescent cells was markedly reduced with fast neutrons, especially at higher doses of radiation. Potentially lethal damage repair by total and quiescent cells was inhibited more strongly with neutrons than with x-rays. When using fast neutrons, the radiosensitivity of solid tumors depends on their heterogeneity less critically than for x-rays. PMID- 7993652 TI - Radiation tolerance of the liver in relation to the preserved functional capacity. AB - The radiation tolerance of the liver was investigated in 12 patients, 11 of them with liver cirrhosis, treated for hepatocellular carcinoma by partial liver irradiation with doses between 50 and 77 Gy. The tolerance was assessed by the complication probability (Lyman's model), which concerned the injured tissue itself, and by a prediction score used for postsurgical liver failure, which concerned the preserved functional capacity, assuming that the > or = 30 Gy volume was equivalent to the resected volume. The prediction score corresponded better with the observed risk of fatal liver failure than the complication probability. The liver volume after radiotherapy correlated largely with the untreated volume and the low-dose volume. Thus the preserved functional capacity gives a better expression of the radiation tolerance than direct measures of the extent of injured tissue. PMID- 7993653 TI - Radiation therapy and concurrent cisplatin administration in locally advanced head and neck cancer. A Hellenic Co-operative Oncology Group study. AB - In an attempt to improve local control of locally advanced head and neck cancer, radiation therapy was combined with cisplatin. Forty-eight patients entered into this study. All patients were irradiated with a 60Co unit and according to the protocol they should receive 70 Gy in the tumor area and 45 Gy in the rest of neck. Cisplatin was administered at a dose of 100 mg/m2 on days 2, 22 and 42. Thirty-seven (80%) patients received the total radiation dose as initially planned. Thirty-four (72%) patients achieved complete and 5 (10%) partial response. Grade 3-4 toxicities included vomiting (14%), stomatitis (4%), diarrhea (2%), myelotoxicity (14%), hoarseness (4%), dysphagia (30%), weight loss (32%), nephrotoxicity (4%) and dermatitis (2%). After a median follow-up of 26 (range, 18-33) months, 16 patients have died. Among the 35 complete responders 6 later on relapsed. Median relapse-free survival has not yet been reached. Combined radiation therapy and cisplatin appears to be a highly active treatment in patients with advanced head and neck cancer as far as primary locoregional response is concerned. PMID- 7993654 TI - Complete remission after repeated trofosfamide treatment in relapsing high-grade malignant non-Hodgkin's lymphoma--a case report. PMID- 7993655 TI - Bronchial embryonal rhabdomyosarcoma--a case report. PMID- 7993656 TI - The methylfolate axis in neural tube defects: in vitro characterisation and clinical investigation. AB - We have investigated various micronutrients important to folate metabolism in women with two previous neural tube defect (NTD)-affected pregnancies. Results suggest the disposition of plasma 5-methyltetrahydrofolate (5CH3-H4PteGlu) with respect to dietary intake may differ from that of the control population. It appears that to achieve a given plasma level of 5CH3-H4PteGlu, the population with a history of NTD pregnancies needs to take in more dietary folate than controls. We discuss this in the context of a potential lesion at or upstream from 5,10-methylenetetrahydrofolate reductase (MTHFR). This metabolic axis, which is responsible for the multienzymic conversion of PteGlu to 5CH3-H4PteGlu, has been investigated in a rat model using liver homogenate. The anticonvulsant drug (ACD) carbamazepine was found to inhibit the reaction in terms of a reduced Vmax and increased Km. Inhibition approaching maximal was found to occur at therapeutic levels of ACD. Various potential inhibitory sites along the methylfolate axis are considered and possible relationships to congenital malformations discussed. We describe folate and one carbon metabolism in relation to potential NTD lesion sites, not only in the light of present findings, but with respect to the published findings of other workers. Based on our hypothesis that an NTD lesion exists upstream from MTHFR, we expound how pteroylmonoglutamate supplementation may protect against NTD (i) by reducing endotoxic homocysteine and (ii) through inhibiting MTHFR (as do dihydrofolates) and thus diverting one carbon units into DNA thymine. PMID- 7993657 TI - Isolation of a new gene in the Friedreich ataxia candidate region on human chromosome 9 by cDNA direct selection. AB - The Friedreich ataxia (FRDA) locus is localized on chromosome 9q13 in an interval less than 1 Mb between markers D9S202/FR1 and FR5. We cloned the FRDA candidate region in YACs, and we started a systematic search for transcripts in this region using the cDNA selection approach. Several overlapping cDNA clones mapping near the telomeric end of the FRDA minimum genetic region were isolated. Zoo blot analysis demonstrated that these cDNAs are well conserved among different species. A transcript of 4.8 kb was identified by hybridization to a Northern blot containing human brain poly(A)+ RNA. Partial sequence of these clones showed 100% homology with a previously described anonymous brain cDNA (EST01251). A search for mutations of this gene in FRDA patients and carriers is in progress. No mutations have been found to date, but we have identified a DNA polymorphism. This polymorphism was nonrecombinant with the disease in a previously described FRDA pedigree in which a recombination had occurred with more telomeric markers. PMID- 7993658 TI - Studies on human porin. XII. Eight monoclonal mouse anti-"porin 31HL" antibodies discriminate type 1 and type 2 mammalian porin channels/VDACs in western blotting and enzyme-linked immunosorbent assays. AB - Eight mouse monoclonal antibodies directed against the acetylated N-terminal part of the type 1 human VDAC Porin 31HL clearly discriminate type 1 and type 2 mammalian porin channels. This is shown by comparing synthetic N-terminal peptides of either channel type in Western dot blots or by ELISA. The data support the specificity of the anti-Porin 31HL antibodies and thus give further support to our recent observations on extramitochondrial expression of VDAC. In the plasmalemma of different mammalian cells VDAC forms part of an ubiquitous chloride channel complex, which in patch clamp measurements may figure as the outwardly rectifying depolarization-induced chloride channel that is affected in cystic fibrosis. PMID- 7993659 TI - Erythropoietin (EPO) levels in fetal rats after ritodrine and terbutaline administration. AB - Beta-2 sympathomimetics, such as terbutaline, have been shown to alter erythropoietin (EPO) secretion in animal studies. More recently introduced sympathomimetics, such as ritodrine, have been extensively used to inhibit uterine contractions in preterm labor. It has not been determined what effect ritodrine may have on EPO production. We investigated the effect of RD administered to rats in the last day of gestation on the dam and the fetuses' levels of EPO. Rats at the 20th day of gestation were given, under anesthesia, either 3000 micrograms/kg ritodrine over a 10-min period or a similar volume of saline as control (CTL). Fetuses were removed at 0 and 4 h after injection. Ritodrine administration produced a decrease of dam EPO (23.4 +/- 4.2 to 12.0 +/- 2.9 pmol/ml), while the CTL showed no changes. The fetuses from the ritodrine injected dams exhibited a marked decline over the 4-h period, while the CTL fetuses did not change. In other experiments 500 micrograms terbutaline was administered daily during the last 5 days of rat gestation. The drug produced a significant decline in EPO at delivery time, but plasma EPO in the pups was unchanged. Blood hematocrits were comparable to those of controls. The data show that acute administration of ritodrine reduces fetal and dam plasma EPO, while long-term terbutaline treatment late in gestation alters maternal, but not fetal plasma EPO, indicating that neither drug has any direct regulatory effect on the erythropoietic ability of the fetuses. PMID- 7993660 TI - Membrane fluidity is different in intact erythrocytes and ghost membranes. AB - The fluorescence anisotropy of 1,6-diphenylhexatriene (DPH) and trimethylammonium DPH in the membranes of intact human erythrocytes and ghost membranes was compared. The anisotropy of fluorophores is significantly higher in intact erythrocytes compared to that in ghost membranes. Perturbation of membranes by heating at 47 degrees C and use of a rotating stirrer affected the anisotropy of fluorophores in intact erythrocytes only. These results suggest that: (a) spectrin has a significant modulating effect on membrane fluidity, and (b) the physical properties of the cell membrane are different between intact erythrocytes and erythrocyte ghost membranes. PMID- 7993661 TI - A Caucasian family with the 3271 mutation in mitochondrial DNA. AB - The second most common mutation associated with MELAS (mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes) in Japan is the 3271 mutation. This mutation was found in a Brazilian family of Portuguese and Italian descent, indicating that this mutation also exists in a race other than Japanese. The propositus had mild clinical manifestations atypical of MELAS, suggesting that patients with the 3271 mutation exhibit heterogeneous phenotypic expression as seen in the 3243 mutation. PMID- 7993662 TI - Low efficiency of [14C]galactose incorporation by galactosemic skin fibroblasts: relationship with neurological sequelae. AB - The incorporation of radioactivity from [1-14C]-galactose into TCA-precipitable material was determined in skin fibroblasts derived from 11 galactosemic patients deficient in galactose 1-phosphate uridyl transferase (GALT-). "R" ratios (designated the R phenotype) were defined as the ratio between [14C]galactose incorporation and [3H]leucine incorporation. Results were expressed as a percentage of the controls. In the GALT-strains this ratio varied from strain to strain, presumably depending on the efficiency of the secondary route via the UDP galactose pyrophosphorylase pathway. In 10 GALT-patients without late serious clinical manifestations, the R phenotype varied from 37 to 57% of the control value. In the 11th patient, the R phenotype was only 20% of the control. Thus, we obtained a significantly lower R phenotype in one patient who was distinguished from the others by having very severe delayed neurological complications, although compliance to galactose-free diet was good. We suggest that, in this patient, the development of the UDP-galactose pyrophosphorylase pathway was not sufficient to ensure the availability of enough galactose for the necessary synthesis of glycoproteins and glycolipids. Thus the R phenotype may be an indicator of the risk of late neurological complications. The determination of the R phenotype of GALT-patients may therefore be valuable. However, further investigations of galactosemic patients with neurological complications are required to confirm this relationship. PMID- 7993663 TI - Anabolic effect of human growth hormone: management of inherited disorders of catabolic pathways. AB - The effects of growth hormone treatment and dietary alanine supplementation, individually and in combination, were studied in five patients with organic acidemias. Three patients had propionic acidemia, one had 3-hydroxyisobutyric acidemia, and one had a defect in isoleucine metabolism. Two patients with propionic acidemia had decreased growth hormone secretion in response to provocative stimuli (intravenous L-arginine and oral levodopa or clonidine); the remaining subjects had sufficient growth hormone secretion. Three of four subjects in whom IGF1 was measured showed subnormal concentrations at baseline (including two with normal growth hormone secretory responses). All patients showed an increase in linear growth with growth hormone. In the four patients studied, all had a significant increase in nitrogen retention over baseline with alanine or growth hormone alone, or with the combination of growth hormone and alanine, with a much greater effect of growth hormone. Lean body mass and body fat composition tended to become normal with treatment. Protein tolerance increased, and when the patients' dietary protein intakes were increased between 20 and 60% they maintained positive nitrogen balance, without a significant increase in metabolite excretion. One patient with propionic acidemia expired during the time of the study, following a course of recurrent pancreatitis and an episode of acute basal ganglia infarction. All of the other subjects showed clinical improvement (decreased incidence of ketoacidotic episodes and decreased frequency of hospital admission and school absence) during treatment, and even the patient who expired remained metabolically stable up to and through the terminal event. We conclude that growth hormone may be of value in the management of patients with organic acidemia. PMID- 7993665 TI - Nonisotopic identification of two point mutations in the CYP21 gene responsible for nonclassic 21-hydroxylase deficiency. AB - A simple nonradioactive method was developed for identification of the Pro-30-Leu and Val-281-Leu mutant alleles in the CYP21B gene. Not only does this approach improve mutation analysis for patients with the late onset form of 21-hydroxylase deficiency, but it also decreases problems with interference by the CYP21A pseudogene sequence. PMID- 7993664 TI - DNA sequence analysis of the cytosolic acetaldehyde dehydrogenase gene (Ahd-2) in mouse strains with variable ethanol preferences. AB - Differences in Ahd-2 at the DNA sequence level were characterized in mouse strains with variable ethanol preferences. The 5' region and the region surrounding the active site of Ahd-2 were compared to detect differences which could affect ethanol sensitivity. Only minor differences were found among the strains in the two regions. These differences cannot explain their variable ethanol preference and the implications of sequence identities among the divergent strains in these regions has yet to be determined. PMID- 7993666 TI - 1,3-Dioctanoylglycerol (1,3-DiC8) is as effective as 1,2-dioctanoylglycerol (1,2 DiC8) in priming phospholipase A2 activation in human platelets and neutrophils. AB - In the present study, we investigated the effects of different diacylglycerols in comparison with phorbol 12-myristate 13-acetate (PMA) on eicosanoid-independent phospholipase A2 (PLA2) activation in human platelets and neutrophils. Eicosanoid independent PLA2 activation was measured under conditions where both cyclooxygenase and lipoxygenases were blocked by BW755C. In the presence of PMA (50 nM), the amount of mass arachidonic acid (AA) released represented 400 and 257% of control (without PMA) in A23187-stimulated platelets and neutrophils, respectively, while 1,2-dioctanoylglycerol (1,2-DiC8) and 1-oleoyl-2-acetyl-sn glycerol (OAG) had increased the eicosanoid-independent AA release by 150 and 117 134% of control, in platelets and neutrophils, respectively. Our results further demonstrate that 1,3-dioctanoylglycerol (1,3-DiC8), a poor activator of protein kinase C (PKC), is nearly as effective as diacylglycerols, such as OAG and 1,2 DiC8 (activators of PKC) in priming PLA2 activation, but is less effective than PMA as a priming agent. However, all three diacylglycerols were less effective than PMA as priming agents. Furthermore, diacylglycerols including 1,3-DiC8 exerted a much greater effect on PLA2 activation in platelets than in neutrophils. Neither 1,3-DiC8 nor 1,2-DiC8 and OAG had any significant priming effect on the accumulation of palmitic and stearic acids, while PMA caused a substantial accumulation of these fatty acids in platelets, but not in neutrophils. We also found that exogenously added OAG underwent significant hydrolysis even in unstimulated platelets, but not in neutrophils, suggesting that exogenously added OAG may be readily accessible for diacylglycerol (DAG) lipase/PLA1 in platelets.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7993668 TI - Natural and restorative oral esthetics. Part II: Esthetic treatment modalities. PMID- 7993667 TI - Inhibitory effect of fatty acids on glucose and insulin uptake in the perfused rat hindquarter. AB - To elucidate the effects of fatty acids on the uptake of glucose and insulin in the muscle, the effects of oleic and palmitic acids on the uptake of glucose and insulin were investigated in perfused hind-quarters of rats. In the absence of insulin, glucose uptake in the hindquarter was slightly, but not significantly, decreased by the addition of oleic and palmitic acids. In the presence of 100 or 500 microU/ml insulin, glucose uptake in the hindquarter (243 +/- 58 or 282 +/- 65 mumol/30 min) was significantly decreased by the addition of 1000 microM oleic acid and 500 microM palmitic acid (175 +/- 50 or 207 +/- 47 mumol/30 min). The decrease in insulin uptake rate, although not significant at 500 microU/ml insulin, is of similar magnitude to the decrease in glucose uptake. In the presence of 1000 microU/ml insulin, glucose and insulin uptake was not significantly altered by the addition of fatty acids. These results indicate that fatty acids directly inhibit the muscular glucose uptake via the decrease in muscular insulin uptake at a physiological concentration of insulin. PMID- 7993669 TI - The golden proportion revisited. PMID- 7993670 TI - Guided bone regeneration for enhanced esthetics: defining the therapeutic possibilities. PMID- 7993671 TI - Esthetic principles for full crown restorations. Part II: Provisionalization. PMID- 7993672 TI - Effect of implant position on implant restoration design. PMID- 7993673 TI - Environment/behavior interface. PMID- 7993674 TI - Shade selection. PMID- 7993675 TI - Solving restorative esthetic dilemmas with the semilunar coronally positioned flap. PMID- 7993676 TI - Esthetic considerations of the long face syndrome. Part I: Class II malocclusion. PMID- 7993677 TI - Esthetic considerations of the long face syndrome. Part II: Class III malocclusion. PMID- 7993678 TI - Esthetic occlusal composite resin restorations. PMID- 7993679 TI - Esthetics and the argon ion laser. PMID- 7993680 TI - Esthetic dentistry challenges to reimbursement. PMID- 7993681 TI - Abstracts and selected papers from the 1993 annual meeting of the Laboratory of Tumor Cell Biology. August 22-28, 1993, Bethesda, Maryland. PMID- 7993683 TI - An excerpted version of the banquet presentation of Dr. Antonia C. Novello, M.D., M.P.H. 1993 Annual Meeting of the Laboratory of Tumor Cell Biology. PMID- 7993682 TI - Identification of factors that govern HIV-1 replication in nondividing host cells. PMID- 7993684 TI - Programmed cell death (apoptosis) and AIDS pathogenesis. PMID- 7993686 TI - [Impervious disposable fabric prevents spread of bacteria. Nurses want disposable clothing. Interview by Kjell Arne Bakke]. PMID- 7993685 TI - SIV transmission across the mucosal barrier. PMID- 7993687 TI - [Impervious disposable fabric prevents spread of bacteria. Air pollution causes postoperative wound infection. Interview by Kjell Arne Bakke]. PMID- 7993688 TI - [Impervious disposable fabric prevents spread of bacteria. Current regulations. Interview by Kjell Arne Bakke]. PMID- 7993689 TI - [Questionable drug distribution]. PMID- 7993691 TI - [Nursing under a different sky: Kotka]. PMID- 7993690 TI - [Questionable drug distribution. Shift in routine. Interview by Karin Anne Aase]. PMID- 7993692 TI - [Open care in psychiatry. Interview by Marit Fonn]. PMID- 7993693 TI - [New center for rare diseases. Interview by Marit Fonn]. PMID- 7993694 TI - [With a balloon for a stomach. Interview by Marit Fonn]. PMID- 7993695 TI - [Happiness and worry. Interview by Marit Fonn]. PMID- 7993696 TI - [Life on a diet. Interview by Marit Fonn]. PMID- 7993697 TI - [Danish hospital on the way against chaos]. PMID- 7993698 TI - [10 steps to better quality of life for children]. PMID- 7993699 TI - [Impervious disposable fabric prevents spread of bacteria. An almost germ-free operating room. Interview by Kjell Arne Bakke]. PMID- 7993700 TI - Systemic lupus erythematosus and Sjogren's syndrome. PMID- 7993701 TI - Pediatric and heritable disorders. PMID- 7993702 TI - Lymphocytes, cytokines, inflammation, and immune trafficking. AB - Patients with systemic lupus erythematosus display heterogeneous immune cell abnormalities that are now being understood in terms of the underlying molecular defects. The fraction of T cells that are involved in the pathogenesis of the disease is characterized in terms of T cell receptor expression, production of inappropriate quantities of lymphokines, and ability to provide help to B cells to produce autoantibodies. The function of antigen-presenting cells is studied in terms of presenting antigens and providing the proper costimulation to T cells. Better understanding of aberrant expression of adhesion molecules may set forward an abnormal tissue response and eventually the expression of clinical disease. PMID- 7993703 TI - Autoantibodies in systemic lupus erythematosus. AB - Various autoantibodies are found in systemic lupus erythematosus. Anti-double stranded DNA antibodies are the most pathognomonic and among the most extensively studied. Genetic studies of these antibodies and their idiotypes suggest that high-affinity IgG anti-double-stranded DNA antibodies are produced by a process of somatic mutation and clonal expansion favoring sequences with accumulated positively charged amino acids in the complementarity-determining regions. The antigens that trigger this process are not known, but recent studies have suggested that a DNA-protein complex may be implicated. At the tissue level, these antibodies may react directly with membrane proteins or indirectly via complexes with DNA, histones, and heparan sulfate. Serologic studies have sought to establish links between clinical features and the presence of particular non DNA-binding autoantibodies. Of particular interest have been antibodies to proteins with nucleic acid-binding potential, such as Sm, SS-A (Ro), and SS-B (La). PMID- 7993704 TI - Epidemiology, genetics, etiology, and environment relationships of systemic lupus erythematosus. AB - Systemic lupus erythematosus continues to provide a major etiologic challenge. Current investigation is focusing on the possibilities of environmental factors, including infection. How these factors are related to genetic factors, including the major histocompatibility complex and more recently observed defects in apoptosis genes, remains unclear. Ethnic and geographic studies of systemic lupus erythematosus are providing important clues, as are continued clinical observations on the various subsets of disease and the patterns of therapeutic response. Different pathogenic mechanisms are constantly being uncovered and in turn need to be related to the various etiologies. PMID- 7993705 TI - Clinical features of systemic lupus erythematosus. AB - Case reports, case series, and analytical clinical research studies continue to define and refine our understanding of the clinical presentation of lupus and its evolution over time. Major areas of interest in the past year have included malignancies, osteoporosis, neonatal lupus, central nervous system lupus, pregnancy, and renal disease. New emphasis has been placed on the importance of gynecologic malignancies in systemic lupus erythematosus. Osteoporosis, especially the role of corticosteroid therapy in the development of osteoporosis, remains a controversial area, particularly in premenopausal women. The poor outcome of many infants with neonatal lupus has been documented in several reports. A more sensitive brain imaging test for central nervous system lupus- brain single photon emission computed tomography--has been introduced. The effect of pregnancy on disease activity and the appropriate use of second-line agents in pregnancy have been reviewed. The importance of hypertension and other clinical variables in predicting renal outcome (as opposed to reliance on renal biopsy findings) was emphasized in two studies. PMID- 7993706 TI - Indicators of disease activity, prognosis, and treatment of systemic lupus erythematosus. AB - In this article, assessment of disease activity in systemic lupus erythematosus (SLE), including available instruments and their use in patients with SLE, is discussed. Several validated measures, including the SLAM (Systemic Lupus Activity Measure), SLEDAI (Systemic Lupus Erythematosus Disease Activity Index), LAI (Lupus Activity Index), ECLAM (European Consensus Lupus Activity Measurement), and that of the BILAG (British Isles Lupus Activity Group) are now available and should be included in studies of new laboratory measures, therapeutic trials, and studies of outcome and prognosis. The prognosis of SLE has improved over the past 4 decades, including 20-year survival rates. With improved survival, other outcome measures such as specific organ function and health status need to be considered. Administration of hydroxychloroquine remains an important part of therapy for SLE. The use of cyclophosphamide should be reserved for severe manifestations of the disease. Newer forms of therapy, particularly immunotherapy, have been tested in animal models. PMID- 7993707 TI - Antiphospholipid antibodies in systemic lupus erythematosus. AB - Antiphospholipid antibodies (aPL) are associated with a clear but variable risk for thromboses at multiple vascular sites and with a wide spectrum of clinical features comprising both the primary and secondary antiphospholipid antibody syndromes (APS). The recent literature reviewed here includes refined and more quantitative descriptions of aPL-associated clinical phenomena and APS features in studies of increasingly larger patient cohorts, and better understanding of the heterogeneity of aPL relative to binding dependency on beta 2 glycoprotein I and other phospholipids. There is expanded knowledge of pathogenesis of aPL from in vitro and in vivo studies in murine and human models and intriguing data on therapeutic modalities, old and new. PMID- 7993708 TI - Epidemiology, pathogenesis, animal models, and treatment of Sjogren's syndrome. AB - Sjogren's syndrome is characterized by dry eyes (xerophthalmia) and dry mouth (xerostomia). Although general agreement exists about the ocular features of Sjogren's syndrome, significant controversy surrounds the classification criteria for defining the oral component. This has resulted in confusion in both the clinical and the research literature. The recent litigation involving silicone breast implants has forced clinicians to evaluate critically whether the condition of a particular patient fulfills specific diagnostic criteria for Sjogren's syndrome. Research studies have focused on potential genetic and environmental factors in the pathogenesis of Sjogren's syndrome. Studies of various ethnic populations have demonstrated an association with particular HLA DR and -DQ alleles. However, the associated alleles are different for each ethnic group. No single environmental agent has been identified as a critical cofactor. Studies have concentrated on herpesviruses (Epstein-Barr virus and human herpesvirus type 6), hepatitis C virus, and retroviruses. Epstein-Barr virus isolated from patients has altered the ability to transform and lytically infect particular types of lymphocytes. Hepatitis C can lead to sicca symptoms, even in patients with relatively normal salivary gland biopsy findings. One report of Japanese patients indicated the presence of human T cell lymphotropic virus type I-like tax genes in the salivary biopsy specimens of a subset of patients and no gag, pol, or env sequences; this finding suggested a potential infection by a defective retrovirus. Studies on the pathogenesis have indicated that cytokines produced in the salivary gland are similar to T helper type 1 lymphocytes (interferon gamma).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7993710 TI - Rheumatic diseases of children, including systemic lupus erythematosus, dermatomyositis, scleroderma, and fasciitis. PMID- 7993709 TI - Chronic arthritis in children. AB - Chronic inflammatory arthritides in children include a wide range of various diseases. One of the main concerns of physicians who treat these disorders is the risk of permanent physical disability resulting from joint damage. Actual classification relies mainly on clinical features, particularly the number of joints affected at onset, although the general feeling is that chronic childhood arthritis exists in many different entities gathered together under the common names juvenile chronic arthritis or juvenile rheumatoid arthritis. The past 2 years were rather fertile in debates for proposing a progression for more objectivity in nomenclature, which was the theme of the Pediatric Rheumatology Study Group session at the American College of Rheumatology annual meeting held in Atlanta in 1992. The viewpoints from North America and Europe addressed at this meeting were published in a supplement of the Journal of Rheumatology in 1993. A debate on this topic was also organized at the International League Against Rheumatism Congress held in Barcelona in 1993. At present, the main criteria rely on clinical experience and natural history of the diseases and on biology and immunogenetics. Another important concern among pediatric rheumatologists is efficacy of treatment. Questions include, "Are we doing enough?" and "How safe are the therapeutic strategies?" In this review some of the recent studies that may be important for classification and nomenclature and therapy and management are discussed. PMID- 7993711 TI - Neonatal lupus syndromes. AB - Neonatal lupus continues to generate considerable interest despite its rarity; more than 15 original contributions were made to the literature in the past year. Diverse aspects of this "syndrome" of passively acquired autoimmunity have been covered. Experiments using a rabbit model provided insights into the pathogenicity of maternal anti-Ro/SS-A and anti-La/SS-B antibodies. Perfusion of rabbit hearts with anti-Ro/SS-A and anti-La/SS-B sera resulted in conduction abnormalities in whole adult rabbit hearts and induced a reduction in the peak slow inward current in patch-clamp experiments of isolated rabbit ventricular myocytes, suggesting involvement of calcium channels. Clinical investigations are moving away from case reports, and recent studies now include substantial entries. Assuming that patients reported from the United States, Finland, and England are all separate, sera from at least 100 different mothers of infants with congenital heart block have been studied. Although there is apparently no serologic profile that is unique to mothers of affected children, compared with mothers of healthy children, anti-Ro/SS-A antibodies (anti-52-kD antibodies are more prevalent by immunoblot in congenital heart block, although all these sera are likely to have anti-60-kD antibodies by immunoprecipitation) are usually of high titer and associated with anti-La/SS-B antibodies. To date, the only maternal autoantibodies that have been associated with congenital heart block recognize Ro/SS-A or La/SS-B antigens. Mothers of affected infants are often asymptomatic, and when symptomatic, the clinical features are frequently characteristic of Sjogren's syndrome. Although treatment of affected fetuses with dexamethasone has successfully diminished associated effusions, there has been no report of reversal of established third-degree heart block. PMID- 7993712 TI - Vasculitis, Kawasaki disease, and hemolytic uremic syndrome. AB - Aside from Henoch-Schonlein purpura and Kawasaki disease, vasculitis in childhood is rare. The etiology, clinical characteristics, and therapy of Kawasaki disease continue to be important areas of investigation, and a number of important observations recently were published. Recent clinical descriptions of other vasculitis disorders such as cutaneous polyarteritis and Wegener's granulomatosis are also reviewed in this article. Hemolytic uremic syndrome is an acute disorder of childhood characterized by thrombocytopenia, microangiopathic hemolytic anemia, and acute nephropathy. Treatment of children with severe manifestations of hemolytic uremic syndrome with plasma exchange therapy in addition to traditional supportive approaches is proving to be life saving in many cases. PMID- 7993713 TI - Infectious arthropathies and other rheumatologic manifestations of infectious diseases. AB - Infectious agents have been implicated in the pathogenesis of many rheumatologic diseases. In most of these diseases, including those in which specific organisms are known to play a role, the details of pathogenesis remain incompletely defined. Recent studies have aimed to isolate bacterial and viral pathogens from patients with rheumatic diseases, efforts have been made to further define the host immune response to infection, and there have been attempts to develop improved methods of diagnosis and treatment of infectious diseases affecting the musculoskeletal system. This review discusses recent studies on the association of infection with illnesses affecting the joints and musculoskeletal system, with an emphasis on the rheumatic diseases of childhood. PMID- 7993714 TI - Progress in diagnosing and understanding chronic pain syndromes in children. AB - Chronic pain syndromes such as fibromyalgia and reflex sympathetic dystrophy constitute an increasing percentage of new patient referrals to pediatric rheumatology clinics. It is surprising then that so few studies have been published on these syndromes. This review focuses on the investigations that are central to our understanding of this difficult diagnostic area. PMID- 7993716 TI - AIDS surveillance in the Americas. PMID- 7993715 TI - Nutritional situation in the Americas. PMID- 7993719 TI - Plasma substitute may improve calcium levels, clot formation. PMID- 7993717 TI - Cuban epidemic neuropathy. An update. PMID- 7993718 TI - Leishmaniasis in the Americas. PMID- 7993720 TI - Taxotere shows significant antitumor activity in anthracycline-resistant breast cancer patients. PMID- 7993721 TI - Lahey Clinic to lead study of treatment options for older women with breast cancer. PMID- 7993722 TI - Possible guide for treatment of AIDS and other diseases. PMID- 7993723 TI - Is bone marrow purging proving to be of value? AB - Although the role of hematopoietic stem-cell transplantation (HSCT) in cancer treatment is rapidly expanding, decreasing the side effects of stem-cell infusion is a major challenge. Cancer cells present in the stem-cell collection can cause relapse after autologous transplantation. In allogeneic transplantation. T lymphocytes contribute to graft-versus-host disease. Various methods of purging have been used to remove these unwanted cells, and there is some evidence that such manipulations are clinically useful. Nevertheless, the inability to detect minimal disease makes it difficult to determine whether relapse is caused by incomplete disease eradication in the patient or by the infused cells. This makes it hard to justify the clinical benefit of ex vivo purging. Researchers can focus on this issue by designing studies with minimal variation in other factors that affect the success of stem-cell transplantation. PMID- 7993724 TI - Clinical trials referral resource. Rectal cancer. PMID- 7993725 TI - Current management of disseminated intravascular coagulation. AB - Disseminated intravascular coagulation is a complex process seen in a wide variety of clinical disorders. The oncology patient may develop this syndrome either as a result of the neoplasm itself or of the treatment of the neoplasm. An understanding of the pathophysiology of disseminated intravascular coagulation is essential for diagnosis and treatment. Diagnosis is accomplished by correlating clinical and laboratory data. Treatment remains controversial, but reversal of the triggering mechanism is the single most important factor in successful treatment. Other interventions, including the use of heparin, antithrombin III, and hirudin, are being studied. Much remains to be understood about disseminated intravascular coagulation, and controlled clinical trials are needed to define optimal treatment. PMID- 7993726 TI - Another view of the epidemiology of non-Hodgkin's lymphoma. PMID- 7993727 TI - After long lag time, radiation therapy for peptic ulcer increases cancer risk. PMID- 7993729 TI - Study reports increase in autotransplants for breast cancer patients in North America. PMID- 7993728 TI - AM285 demonstrates anticancer activity in combination with conventional agents. PMID- 7993730 TI - Lymphedema reduction by noninvasive complex lymphedema therapy. AB - Noninvasive complex lymphedema therapy (CLT), a technique of manual lymph drainage, compressive bandaging, and specific physical therapy exercises, has been utilized successfully to treat lymphedema in Europe and Australia. This paper reports the results of such therapy in 38 patients (16 females with arm lymphedema secondary to breast surgery, 18 patients with unilateral lower extremity lymphedema, and 4 individuals with bilateral leg disease) for 1 month. Reduction of edema averaged 73% among the patients with arm disease, and 88% among those with leg lymphedema; both reductions are statistically significant. Thirty patients have been followed for up to 1 year. During this period, their average reduction in lymphedema of 80% improved to 86%. We conclude that CLT significantly and safely reduces lymphedema. Reductions not only are maintained after the initial therapy but may increase in magnitude. PMID- 7993731 TI - World malaria situation in 1992. Part I. PMID- 7993732 TI - Recognising outbreaks of tuberculosis. PMID- 7993733 TI - Promoting mental health behind bars. PMID- 7993734 TI - Space science: the final frontier. PMID- 7993735 TI - Assessing the cost of pressure sores. PMID- 7993736 TI - Dementia in acute units: the issues. AB - To coincide with World Alzheimer's Day, Nursing Standard this week launches a major new series which looks in detail at one of the most pressing nursing problems of the age--coping with the behaviours of people with dementia who are admitted to acute care units. The series, which consists of seven articles, presented at monthly intervals, takes a very practical look at how nurses in such units can cope with patients who display behaviours such as wandering, aggression, sexual disinhibition and agitation--behaviours which nurses have difficulty understanding and managing.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7993737 TI - Local pay: is it set to become a reality? PMID- 7993738 TI - Preparing to take on clinical supervision. PMID- 7993739 TI - Live and let die? PMID- 7993740 TI - Selling nursing: come out and fight. PMID- 7993741 TI - Probing reports. PMID- 7993742 TI - Nursing ethics. III: Ideas of self (continuing education credit). PMID- 7993743 TI - Depression rife among Ugandan nurses, AIDS conference is told. PMID- 7993744 TI - Programmable pumps for people who can't cope alone. PMID- 7993745 TI - Personalising the service. PMID- 7993747 TI - Revision surgery for joint replacements. AB - Revision joint surgery is becoming an increasingly common operation. This article describes how the operation is carried out, the techniques available and the pre operative, peri-operative and post-operative nursing care of the patient. PMID- 7993746 TI - Programme for NVQ makes the grade. PMID- 7993748 TI - Mental health: meeting the needs of neglected patients. AB - This article discusses part of a study of a large, well-resourced community care service. The study looked at why people with serious, ongoing mental health problems were sometimes rejected by the service or refused the care they were offered. The authors argue that these patients need the support of mental health care services although they can be difficult to care for, and suggests ways in which this can be achieved. PMID- 7993749 TI - Leg ulcer treatments: a critical review (Part 2). PMID- 7993750 TI - Education: hands off experience. PMID- 7993751 TI - Waiting areas: cosmetic surgery. PMID- 7993752 TI - Support: baptism by fire. PMID- 7993753 TI - Speaking out: tongue-tied. PMID- 7993754 TI - World Mental Health Day. Universal challenge. PMID- 7993755 TI - World Mental Health Day. Must do better. PMID- 7993756 TI - The diet dictators. PMID- 7993757 TI - Professional development: don't call me stupid. PMID- 7993758 TI - Employment issues: share and share alike. PMID- 7993760 TI - Nursing quality in Sweden. PMID- 7993759 TI - Nursing ethics. IV: Theories and principles (continuing education credit). PMID- 7993761 TI - One-stop quality. PMID- 7993762 TI - Euroquan comes of age. PMID- 7993764 TI - Towards quality in Luxembourg. PMID- 7993763 TI - Quality issues and nursing education. PMID- 7993765 TI - Concerted action on quality. PMID- 7993766 TI - Small team care approach increases patient satisfaction. PMID- 7993767 TI - Zidovudine cuts HIV transmission rates. PMID- 7993768 TI - Emergency services: leather-clad lifesavers. PMID- 7993769 TI - The Pit Stop initiative. PMID- 7993770 TI - Extending nurses' professional roles. PMID- 7993771 TI - A guide to setting up patient-focused care. PMID- 7993772 TI - A guide to documents on the NHS reforms. AB - The convulsive changes which have swamped the health services in recent years have been preceded by reports, documents and commentaries. An understanding of what information is contained where is important in helping nurses come to terms with the reforms and their implications for patients and nursing practice. This review sets out the most significant publications, their main points, and where they can be obtained. PMID- 7993773 TI - Absenteeism: cashing in on sickness. PMID- 7993774 TI - Mental health: taking a punch. PMID- 7993775 TI - Student uprising. PMID- 7993776 TI - Sister Susie. A phone-fayre. PMID- 7993778 TI - Theatre nursing. Pearls of wisdom. PMID- 7993779 TI - Theatre nursing. Operation Sarajevo. PMID- 7993777 TI - Theatre nursing. Empowerment, empowerment.... PMID- 7993780 TI - Theatre nursing. Real nursing, for real nurses. PMID- 7993781 TI - Nursing ethics. V: Points of view (continuing education credit). PMID- 7993782 TI - Nurses fight 'patient-approved' closure of HIV/AIDS ward. PMID- 7993783 TI - Simple analgesics: choosing with care (continuing education credit). PMID- 7993784 TI - Antisense therapeutics in haematological malignancies. PMID- 7993785 TI - Studies of neutrophil and monocyte oxidative responses in polycythaemia vera and related myeloproliferative disorders. AB - We have previously reported that polymorphonuclear granulocyte (PMN) chemiluminescence (CL) and superoxide anion production are abnormally low in patients with polycythaemia vera (PV) after simulation with n-formyl-methionyl leucyl-phenylalanine (fMLP), but normal when elicited by phorbol myristate acetate (PMA). This study documents that both fMLP and PMA induced CL was normal in PMN from patients with chronic myelogenous leukaemia (CML) and essential thrombocythaemia (ET). Furthermore, we monitored intracellular hydrogen peroxide (H2O2) production in PMN and monocytes from patients with PV, CML and ET by flow cytometry. H2O2 production in resting and PMA-stimulated cells was normal in all diseases. So also was fMLP induced H2O2 generation in ET PMN and monocytes. In contrast, fMLP-induced H2O2 production was significantly lower both in PV PMN (1.8 +/- 0.7 mean fluorescence intensity units in PV compared to 8.4 +/- 3.4 in healthy controls; P < 0.02), and in PV monocytes (0.3 +/- 0.5 compared to 2.5 +/- 0.7 in controls; P < 0.02). A less pronounced reduction of fMLP stimulated H2O2 production was noted in CML PMN (3.8 +/- 3.1 compared to 8.4 +/- 3.4 in controls; P < 0.05), and monocytes (1.3 +/- 0.6 compared to 2.5 +/- 0.7 in controls; P < 0.05). The reduction of H2O2 generation in PV and CML PMN was not attributed to subpopulations of less responsive cells. However, one ET and one CML patient showed a subpopulation of less responsive PMN. Thus intracellular H2O2 (as well as extracellular release of superoxide ions) is reduced in fMLP-stimulated PV PMN and monocytes but normal after PMA stimulation, a phenomenon that is not consistently found in other myeloproliferative disorders. PMID- 7993786 TI - Spontaneous megakaryocyte colony formation in myeloproliferative disorders is not neutralizable by antibodies against IL3, IL6 and GM-CSF. AB - Megakaryocyte progenitor growth in 42 patients with myeloproliferative disorders (MPD), including 23 essential thrombocythaemia (ET), eight polycythaemia vera (PV), six chronic myelogenous leukaemia (CML) and five primary myelofibrosis (PMF), was studied in vitro using plasma clot assay and serum-free agar culture. Spontaneous megakaryocyte colonies (CFU-MK) were found in 34/40 (80%) blood and 14/18 (77.8%) bone marrow plasma clot cultures, and also observed in 27/35 (77.1%) blood and 10/18 (55.6%) bone marrow serum-free agar cultures. In the blood of 27 patients with MPD (15 ET, four PV, four CML and four PMF) and the bone marrow of 10 patients (five ET, four CML and one PV), spontaneous colony formation was observed in both plasma clot and serum-free agar cultures. However, spontaneous CFU-MK was only found in plasma clot culture, but not in agar culture in two blood (one ET and one CML) and four bone marrow cultures (one ET, two PV, one CML). The colony numbers were greatly increased in the presence of aplastic anaemia serum (AAS) under both conditions. In 17 patients (12 ET, two CML and three PV) with spontaneous megakaryocyte colonies, anti-cytokine antibody neutralizing experiments were carried out in blood cultures. Anti-IL3, anti-IL6 and anti-GM-CSF antibody, alone or in combination, at different concentrations (1, 5 and 10 micrograms/ml), were added into plasma clot or agar cultures without exogenous stimulating growth factors. The results showed that the numbers of spontaneous megakaryocyte colonies were not significantly decreased in the presence of these monoclonal antibodies in the cultures. The data indicated that the megakaryocyte progenitor growth in MPD under in vitro conditions was heterogenous, and independent of exogenous stimulatory factors in most patients and that optimal megakaryocyte colony development in MPD still requires exogenous growth factors. Three possibilities are discussed with regard to the phenomenon that the spontaneous colony formation was not decreased with the addition of anti IL3, anti-IL6 and anti-GM-CSF antibodies. PMID- 7993787 TI - The proliferative activity of myelopoiesis in myelodysplasia evaluated by multiparameter flow cytometry. AB - Double staining of bone marrow cells for CD13 and CD33 leucocyte differentiatian antigens and for DNA content has allowed us to evaluate the proliferative capacity of myelopoiesis in patients with myelodysplastic syndromes (MDS) using flow cytometry. By analysing 39 patients (15 RA/RAS, 14 RAEB and 10 RAEB-t) and eight normal controls, we found significant differences in both the percentage of cells positive for these immature myeloid antigens between the FAB groups as well as in the fractions of CD13 and CD33 positive cells in S or S-G2M phase of the cell cycle. Moreover, a clear decrease in the immature myeloid cell proliferative activity upon progression within the FAB groups was evident. Finally, we found a significant negative association between the percentage of myeloblasts in the bone marrow and the proliferative activity of the immature myeloid cells, indicating that the block in differentiation in MDS patients might be coupled to a simultaneous block in proliferation, especially in advanced stages. These data suggest that the use of double parameter assays in the longitudinal follow-up of MDS patients might yield new information about the biology of MDS. PMID- 7993788 TI - Cell surface expression and functional significance of adhesion molecules on human myeloma-derived cell lines. AB - Multiple myeloma is characterized by the presence of malignant plasma cells predominantly localized in bone marrow. Our prior studies have suggested that human myeloma derived-cell lines adhere specifically to fibronectin and to bone marrow stromal cells (BMSCs) via beta 1 and beta 2 integrins as well as RGD peptide, and that tumour cell to BMSC contact triggers interleukin-6 (IL-6) secretion from BMSCs. Since IL-6 is a growth factor for myeloma, adhesion may be important in paracrine IL-6 mediated tumour cell growth. We therefore examined phenotypic expression of adhesion molecules on the U266 and IM-9 human myeloma derived cell lines using the panel of monoclonal antibodies (MoAbs) directed at adhesion molecules submitted to the Vth International Conference on Human Leukocyte Differentiation Antigens. U266 and IM-9 myeloma cell lines express mainly CD29, CD49d, VLA-1, CD18, CD54, ICAM-2 and ICAM-3. In contrast, CD49b, VLA 3, CD49f, CD11b, VCAM-1, selectins and selectin-ligands were not expressed on these cell lines. Specific adherence of IM-9 cells to BMSC line LP101 was demonstrated which could be partially blocked by pre-incubation and culture of tumour cells with anti-beta 1 integrin, anti-beta 2 integrin, anti-CD49d, anti VLA-5, anti-CD11a, anti-CD44 and anti-CD54 MoAbs. The combination of these MoAbs (anti-CD29, CD18, CD11a, CD49d, VLA-5, CD44, CD54, ICAM-2, ICAM-3 MoAbs) decreased but did not completely abrogate binding of IM-9 to BMSCs. Moreover, increases in IL-6 secretion from BMSCs after adherence of IM-9 cells were also partially blocked by these MoAbs. These findings suggest that multiple adhesion pathways may mediate adherence of myeloma cell lines to BMSCs, localizing tumour cells in the marrow microenvironment and triggering IL-6 secretion by BMSCs which may augment tumour cell growth. PMID- 7993789 TI - Generation of anti-tumour activity by OKT3-stimulation in multiple myeloma: in vitro inhibition of autologous haemopoiesis. AB - T cells in multiple myeloma (MM) patients are highly susceptible to activation with the anti-CD3 monoclonal antibody (mAb) OKT3. When short-term OKT3 stimulation is carried out on bone marrow mononuclear cells (BMMC), large numbers of CD3+ CD25+ HLA-DR+ cells are rapidly generated and autologous malignant plasma cells are killed. OKT3 may thus be exploited in autologous bone marrow transplantation (ABMT) to purge residual plasma cells and simultaneously activate T cells to induce graft-versus-leukemia-like (GVL-like) activity upon reinfusion. However, the possible impact of ex-vivo short-term OKT3 stimulation on haematological recovery is unknown. The aim of this work was to investigate the effect of OKT3 stimulation in vitro on autologous haemopoietic progenitor cells (HPC) of MM patients. Colony formation by granulocyte-macrophage progenitor cells (granulocyte-macrophage colony-forming units, CFU-GM) was highly suppressed, although supernatants of OKT3-activated T cells contained up to 2,500 pg/ml of granulocyte-macrophage colony-stimulating factor (GM-CSF). T cell depletion completely prevented this suppression. Neutralizing antibodies against TNF-alpha, TNF-beta and IFN-gamma (which are also produced by OKT3-activated MM T cells) did not prevent it, and Transwell cultures showed that cell-to-cell contact was the main mechanism involved. OKT3-activated T cells also suppressed erythroid burst forming units (BFU-E) and CFU-GM generation from HPC responsible for long-term maintenance of in vitro myelopoiesis. When tested on normal allogeneic BM, MM supernatants of OKT3-stimulated BMMC partially suppressed the generation of day 7 CFU-GM, but had no effect on day 14 CFU-GM. These data indicate that short-term stimulation of BMMC with OKT3 can be used to generate anti-tumour effector T cells for autologous adoptive immunotherapy. It is not a feasable approach for ex vivo purging and activation procedures in ABMT because of its potent inhibition of autologous haemopoiesis. PMID- 7993790 TI - P-glycoprotein expression on acute myeloid leukaemia blast cells at diagnosis predicts response to chemotherapy and survival. AB - P-glycoprotein (Pgp) expression, which is associated with the multi-drug resistance (MDR) phenotype, has been reported to be a useful predictor of treatment outcome in acute leukaemia. We have examined the expression of Pgp on acute myeloid leukaemia (AML) cells in 54 newly diagnosed patients, using a novel streptavidin-biotin complex (ABC) technique. 55% of patients at diagnosis were positive for Pgp with JSB-1, a monoclonal antibody that binds to an internal epitope of Pgp. All patients received intensive induction chemotherapy. Post remission treatment consisted of further chemotherapy +/- bone marrow transplantation. Complete remission (CR) rates were significantly lower in the Pgp positive group than in the Pgp negative group (60% v 92%; P = 0.02). The overall survival for Pgp-positive patients was significantly shorter (329 v 534d, P = 0.004), disease-free survival was also reduced but the difference was not statistically significant (median 277 v 522d, P = 0.16). In this study CD34 expression was not predictive of response to chemotherapy nor was it associated with Pgp expression. Our results confirm the prognostic value of Pgp expression in AML at diagnosis and we suggest that Pgp could be a useful therapeutic target for reversing multi-drug resistance. Furthermore, our simple and sensitive method of detecting Pgp should enable widespread testing to be performed. PMID- 7993791 TI - Minor myeloid component in Ph chromosome-positive acute lymphoblastic leukaemia: correlation with cytogenetic pattern and implication for poor response to therapy. AB - Morphological, immunological and cytogenetic features were studied in 27 adults presenting with Ph chromosome-positive acute lymphoblastic leukaemia (ALL), in correlation with clinical outcome. Twenty patients (group 1) were diagnosed as having typical ALL according to the FAB criteria supported by immunological findings. Less than 1% blast cells with azurophilic granules were detected in all cases. Myeloid cytochemistry, i.e. peroxidase and Sudan black-B stain, was negative in all cases. A minor phenotype deviation consisting of the expression of the CD13 myeloid-associated marker was detected in two patients. In seven patients (group 2) a diagnosis of ALL with a minor myeloid component was made because of the presence of a majority of lymphoid blasts and of 5-15% blast cells with morphological cytochemical and immunological features of the myeloid lineage. Abnormal metaphases were found in 6/20 (30%) patients in group 1, compared with 7/7 (100%) patients in group 2. All patients were treated by antilymphoid regimens; however, complete remission was achieved in 17/20 (85%) patients in group 1 versus 1/7 (14.3%) patients in group 2. Median survival was 16 months, range < 1-120+ in group 1 and 9 months, range < 1-15 in group 2. It is concluded that morphological, immunological and cytogenetic studies allow for the recognition of two cytological subsets of Ph+ ALL. The presence of a minor myeloid component in otherwise typical Ph chromosome-positive ALL may be associated with a distinct cytogenetic pattern and poor responses to antilymphoid therapy. PMID- 7993792 TI - Trisomy 12 is uncommon in typical chronic lymphocytic leukaemias. AB - The incidence of trisomy 12 was studied by conventional chromosome analysis in 111 patients referred as B-cell chronic lymphocytic leukaemia (B-CLL). Fluorescent in situ hybridization (FISH) was also applied in 34 of those patients with either a normal karyotype or no analysable mitoses. By karyotyping, trisomy 12 was present in 11.7% (13/111), whereas additional FISH increased the incidence to 14.4% (16/111). When subdividing our cases in either typical CLL (n = 90), fulfilling the FAB classification criteria, or atypical CLL (n = 21), with one or more variations from those criteria, the incidence of +12 by metaphase analysis was 3% and 48%, respectively. Additional FISH increased the incidence to 4% and 57%. The most common aberration in atypical CLL was FMC7 positivity (n = 11), followed by CD5 negativity (n = 8), strong surface immunoglobulin staining (n = 7) and atypical morphology (n = 6). Trisomy 12 could only be demonstrated in a small proportion of neoplastic cells in all positive cases. By FISH and/or karyotyping, all available samples at diagnosis of the disease were positive. PMID- 7993793 TI - Clinicopathological spectrum of haemophagocytic syndrome in Epstein-Barr virus associated peripheral T-cell lymphoma. AB - Haemophagocytic syndrome (HS) is frequently observed in Epstein-Barr virus associated peripheral T-cell lymphoma (EBV-PTCL) and represents a major cause of death. In this communication we have further analysed the spectrum of HS in 12 patients with EBV-PTCL. The patients could be divided into three groups according to the time of onset of HS during the clinical course of PTCL. Group I patients (four cases) had HS as the initial clinical manifestation. All four patients were initially suspected to have malignant histiocytosis (MH) but a MH-like PTCL was later diagnosed. Group II patients (six cases) developed HS at the time of lymphoma relapse. Four of them belonged to the angioinvasive type PTCL. Group III patients (two cases) developed HS at clinical remission; both were angioinvasive type PTCL. Nine patients had serological evidence suggesting active EBV infection. The clinical course after the onset of HS was generally fulminant in each group with a median survival of only 44d despite combination chemotherapy and/or empirical therapy with high-dose immunoglobulin and corticosteroids in six patients. In conclusion, HS represents a severe complication of EBV-PTCL. Although most patients develop HS at a time of active lymphoma, the syndrome may occur when the lymphoma is in remission. Because of the poor outcome, early diagnosis and a new modality of treatment for HS associated with EBV-PTCL should be pursued in future. PMID- 7993794 TI - Peripheral T cell receptors alpha beta and gamma delta in patients with Hodgkin's lymphoma. AB - Antigen recognition by T cells is determined by an antigen specific T cell receptor (TCR). Two heterodimeric TCR structures associated with CD3 have been defined: TCR alpha beta and TCR gamma delta. TCR alpha beta and its function are well described but the role of TCR gamma delta in normal and lymphoproliferative disorders is not well established. In newly diagnosed or relapsed/refractory Hodgkin's disease (HD), a disease associated with defective T cell functions and increased sIL-2R, we determined levels of seven TCR alpha beta variable regions [beta V5(a), beta V5(b), beta V6(a), beta V12(a), alpha beta V(a), alpha V2(a)] and TCR gamma delta by using monoclonal antibodies (MCA). TCR gamma delta levels did not show any difference, but several variable regions of the TCR alpha beta differed when groups are compared with each other and the control group. PMID- 7993795 TI - Inhibition of prothrombin activation by antiphospholipid antibodies and beta 2 glycoprotein 1. AB - Lupus anticoagulants, commonly found in the immunoglobulin fraction of patients with the antiphospholipid syndrome (APS), and the normal plasma protein beta 2 glycoprotein 1 (beta 2GP1) may both contribute to the in vitro impairment of prothrombin activation associated with the APS. We examined the effects upon prothrombin activation supported by phospholipid vesicles of plasma IgG preparations from APS patients in the presence and absence of beta 2GP1. Using a purified system for measurement of prothrombin activation to thrombin, we demonstrated significant phospholipid concentration-dependent inhibition of prothrombin activation in the absence of beta 2GP1 by 11 consecutive patient IgG preparations. The degree of inhibition of prothrombin activation by equivalent concentrations of patient IgG correlated well with the extent of prolongation of the plasma clotting time in lupus anticoagulant assays of whole patient plasma. Additional studies with eight patient IgG preparations indicated that the addition of beta 2GP1 to patient IgG-phospholipid vesicle mixtures resulted in either independently additive inhibition by the two protein species (six cases) or potential inhibition of beta 2GP1 of the IgG inhibitory activity demonstrable in the absence of beta 2 GP1 (two cases). In addition, beta 2GP1-independent inhibition of prothrombin activation also occurred with three patient IgG preparations obtained by affinity binding to cardiolipin. PMID- 7993796 TI - The progression of HCV-associated liver disease in a cohort of haemophilic patients. AB - We have studied morbidity and mortality related to hepatitis C virus infection in haemophilic patients treated at our centre. 11/255 HCV seropositive patients have developed hepatic decompensation. 20 years after first exposure to lyophilized clotting factor concentrate the risk of hepatic decompensation is estimated to be 10.8% (95% CI 3.8-17.8%). There is a significantly increased risk associated with HIV infection, and also with increased age. For HIV seropositive patients the rates of decline in CD4 lymphocyte count and the development of p24 antigenaemia are significant risk factors for hepatic decompensation. Cirrhosis was seen in 9/19 HIV seropositive patients at post mortem. There was an association of cirrhosis with increased age but not with CD4 count, p24 antigenaemia, or AIDS. In conclusion, HCV infection is associated with serious liver disease in haemophilic patients, but so far this has been restricted to a minority of those at risk. HIV co-infection accelerates progression to hepatic decompensation, and we speculate that this is probably due to enhanced HCV replication in the presence of immune deficiency. PMID- 7993797 TI - An echistatin-like Arg-Gly-Asp (RGD)-containing sequence in the heavy chain CDR3 of a murine monoclonal antibody that inhibits human platelet glycoprotein IIb/IIIa function. AB - We describe the production and biochemical characterization of the first GPIIb/IIIa-inhibiting monoclonal antibody that contains an RGD sequence in the CDR3 region of the heavy chain. Monoclonal antibodies obtained by immunizing mice with human platelets were screened using consecutive ELISAs based on human platelets and immuno-affinity-purified glycoprotein (GP) IIb/IIIa coated on microtitre plates. Out of 30 monoclonal antibodies reacting with GPIIb/IIIa, one, MA-16N7C2, potently inhibited platelet aggregation induced by ADP, thrombin, arachidonic acid, collagen, U46619, adrenaline and platelet-activating factor, whereas ristocetin-induced aggregation was unaffected. MA-16N7C2 (IgG2a) bound approximately 4 times faster to activated than to resting platelets, with a Kdcalc of 6.6nM and of 17.5nM, respectively. Equilibrium binding studies to non activated platelets showed a Kd of 18.2nM with 41 x 10(3) binding sites per platelet. The antibody recognized GPIIb/IIIa only as a Ca(2+)-dependent complex. MA-16N7C2 blocked fibrinogen and von Willebrand factor binding to GPIIb/IIIa in a competitive manner with a Ki of 8.5nM and 13.2nM, respectively. Sequence analysis revealed a RGD-containing sequence with homology to disintegrins, in the CDR3 region of the heavy chain. That this RGD-containing sequence could be involved in the interaction of the antibody to GPIIb/IIIa was finally indicated by showing that the binding is completely and competitively inhibited by echistatin. PMID- 7993798 TI - Improvement of mitomycin C- and cyclophosphamide-induced thrombocytopenia and leucocytopenia by prior treatment with deoxyspergualin in dogs. AB - Deoxyspergualin (DGS) is a new immunosuppressant which has shown inhibitory haemopoietic activity. We investigated the myeloprotective effect of DSG against the haemopoietic injury of mitomycin C (MMC) or cyclophosphamide (CYC) by measuring peripheral blood cell numbers in dogs. DSG given at 5 mg/kg on days 3, 2 and 1 before, or at 10 mg/kg on either days 2 and 1 before or on day 1 before and the day of injection of MMC at 0.25 mg/kg ameliorated both the thrombocytopenia and leucopenia caused by MMC. This ameliorative effect was more evident on platelet counts than on white blood cell counts. In addition, the leucopenia and thrombocytopenia induced by a single injection of CYC at 10 mg/kg was also ameliorated by prior DSG administration. These findings suggest that DSG may be useful in protecting against the haemopoietic damage induced by chemotherapeutic agents in the treatment of cancer. PMID- 7993800 TI - Elevated urinary levels of thromboxane and prostacyclin metabolities in sickle cell disease reflects activated platelets in the circulation. AB - There is evidence for increased factor VII turnover and the associated increased thrombin generation and fibrinolytic activities in sickle cell disease (SCD) that may affect in vivo platelet and endothelial cell reactivity. We studied the release of specific eicosanoids that are indicative of in vivo platelet activation and endothelial cell injury. The circulating and urinary levels of 2,3 dinor thromboxane B2(2,3-dinor-TxB2),TxB2,PGI2 [as 6-keto-PGF1 alpha], and PGE2 were measured in 15HbSS patients, eight HbAA non-haemolytic anaemic individuals and 12 healthy HbAA controls using specific RIAs. The mean urinary 2,3-dinor-TxB2 in the HbSS patients was significantly higher than in both the healthy HbAA and the anaemic controls. 6-keto-PGF1 alpha was undetected in the urines of the healthy HbAA controls, but was measured insignificant amounts in the HbSS and the HbAA anaemic patients. The urinary concentrations of PGE2 and TxB2 in HbSS patients' samples were also significantly higher than those of both control groups (P < 0.05). PGE2 and TxB2 levels were below the detection limit in the plasmas of the HbAA subjects, but were measurable in the HbSS and HbAA anaemic plasmas. The plasma level of 6-keto-PGF1 alpha in the HbSS patients was also significantly higher than in the control groups. The data indicates a persistent inflammatory process in the HbSS patients, and is consistent with the hypothesis that there is platelet and endothelial cell activation in SCD. PMID- 7993799 TI - A case of severe neonatal thrombocytopenia with schizencephaly associated with anti-HPA-1b and anti-HPA-2a. AB - We report a family with a neonate who was severely damaged by intracranial haemorrhages. These probably occurred before the 20th week of gestation. The neonate had a moderate thrombocytopenia. In the maternal serum anti-HPA-1b and anti-HPA-2a alloantibodies were detected. Third-generation assays were applied to identify the alloantibodies. No other cause for the bleeding was found. Probably the combination of anti-HPA-1b and anti-HPA-2a alloantibodies, directed against the platelet fibrinogen receptor and the von Willebrand receptor, respectively, induced a thrombocytopenia and a thrombocytopathy. PMID- 7993801 TI - The painful crisis of homozygous sickle cell disease: clinical features. AB - The details of onset, perceived precipitating factors, associated symptoms, and pain distribution in the painful crisis of homozygous sickle cell (SS) disease have been prospectively recorded in 183 painful crises in 118 patients admitted to a day-care centre in Kingston, Jamaica. Painful crises developed most frequently between 3 p.m. and midnight, most commonly affected patients aged 15 29 years, affected the sexes equally, and were not obviously influenced by menstrual cycle. Of the perceived precipitating factors, skin cooling occurred in 34%, emotional stress in 10%, physical exertion in 7%, and pregnancy in 5% of women of child-bearing age. Cold as a precipitant was not less common in patients with more subcutaneous fat. Pain affected the lumbar spine in 49%, abdomen in 32%, femoral shaft in 30%, and knees in 21%. There was a highly significant excess of bilateral involvement in limb and rib pain. Recurrent painful crises occurred in 40 patients but showed no evidence of involving similar sites on successive occasions. Abdominal painful crises were associated with abdominal distention in 18 (31%) and with referred rib pain in a further 15 (26%) of crises. Fever was common even in apparently uncomplicated painful crises, suggesting that fever is characteristic of the painful crisis itself and not necessarily indicative of infection. Following investigation and treatment in a day-care centre, over 90% of patients returned home. PMID- 7993802 TI - Prevention of MHC-alloimmunization by UV-B irradiation in a murine model: effects of UV dose and number of transfused cells. AB - The optimal dose of UV-B radiation for prevention of in vivo alloimmunization (AI) against major histocompatibility complex (MHC) antigens was investigated in a murine transfusion model. Two groups with five C57BL/6 mice (H-2b) each were transfused at weekly intervals with 1 x 10(5) or 1 x 10(6) DBA/2 (H-2d) leucocytes. Both suspensions induced anti-H-2d antibodies in all mice after the second transfusion. The minimal UV-B dose required for abolition of alloreactivity in the mixed leucocyte reaction (MLR) was 0.6 J/cm2. This dose completely prevented the onset of MHC-AI in all five mice transfused with six suspensions containing 1 x 10(5) leucocytes. In contrast, suspensions with 1 x 10(6) leucocytes and exposed to 0.6 J/cm2 induced immunization in 4/5 mice. Further increase of the dose to 1.8 or 5.4 J/cm2 did not prevent the onset of MHC AI. The use of UV radiation for prevention of secondary MHC-AI was investigated in five mice with a primed immune system. Transfusion of suspensions with 1 x 10(5) leucocytes and irradiated at a dose of 1.8 J/cm2 did not prevent booster reactions. We conclude that the number of leucocytes per transfusion determines the efficacy of UV irradiation for the prevention of MHC-AI. For UV irradiation of human platelet concentrates (PCs) we propose to reduce the number of leucocytes by centrifugation prior to UV exposure. UV-B irradiation of PCs with high numbers of leucocytes may not be effective for prevention of alloimmunization. PMID- 7993804 TI - Red cell lipid abnormalities in acquired acanthocytosis are extended to platelets. AB - Acquired acanthocytosis (AA) is an uncommon disease characterized by the presence of abnormal red cells (acanthocytes) in the blood smears of affected subjects. Acanthocyte membrane is enriched in cholesterol by an abnormal plasma lipoprotein. We studied the existence of similar changes in platelets of one patient with AA. Red cell cholesterol/phospholipid (Ch/PL) ratio in the patient was 1.6 (normal 1.1 +/- 0.1). Phosphatidylcholine (PC) comprised 36% of total phospholipid (30.7 +/- 1.8% in controls). Platelets showed aberrant morphology in the blood smears, and the ratio Ch/PL was high in comparison with normal platelets (1.4 v 0.6 +/- 0.1). PC comprised 52% of total PL (39.6 +/- 1.9% in normal platelets). Normal platelets incubated with autologous plasma for 24 h maintained a Ch/PL ratio of 0.7, whereas this value changed to 1.4 when these cells were incubated with plasma from the patient. These results suggest that platelets of patients affected by AA acquire the same biochemical abnormality as red cells. PMID- 7993803 TI - rh-erythropoietin stimulates immature reticulocyte release in man. AB - The pharmacodynamics of single intravenous dosing with recombinant human erthropoietin (rhEPO) was investigated in eight healthy volunteers (150 U/kg, n = 2; 300 U/kg, n = 6) with respect to reticulocyte subdivisions (by fluorescence flow cytometry) and serum ferritin over 6.5 d. The present study shows that bolus rhEPO injection produces an immediate release of high and middle fluorescence (immature) reticulocytes with a high RNA content from the marrow into the circulation, whereas the low fluorescence (more mature) reticulocytes were at first not affected. Serum ferritin decreased markedly within 24 h, reaching a nadir 50% of baseline after 120 h (5 d), with no increase in haemoglobin. Our data suggests that rhEPO triggers premature expulsion of immature reticulocytes from the bone marrow into the circulation independent of its effect in stimulating erythropoiesis and that rhEPO has an effect on serum ferritin concentration which in this dynamic situation is dependent not only on the iron stores. PMID- 7993805 TI - Burkitt type leukaemia associated with multiple myeloma. AB - We describe a 77-year-old man with multiple myeloma (MM) who developed Burkitt type leukaemia (BTL) 16 months after the initial diagnosis of MM. MM was positive for CD10 with immunoglobulin (Ig) kappa, kappa Bence Jones protein (BJP) and a normal karyotype. BTL was positive for CD10, CD19, CD20 and HLA-DR with Ig mu and lambda, lambda BJP and a clonal abnormal karyotype of 46,XY,-13, t(8;14)(q24;q32),11q+,14q+, +mar. The patient died 9 d after diagnosis of BTL despite treatment with multiple agents. This is, to our knowledge, the first such case to be reported. PMID- 7993806 TI - The in vitro and in vivo effect of recombinant interferon alpha-2a on circulating haemopoietic progenitors in polycythaemia vera. AB - In four patients with polycythaemia vera (PV) who received interferon alpha (IFN alpha) (3 MU subcutaneously three times a week) for 5 months, peripheral blood levels of granulocyte-macrophage colony-forming units and erythroid burst-forming units were assessed monthly. Circulating progenitors significantly decreased throughout the treatment period. Moreover, we observed an inhibitory activity of IFN-alpha on haemopoietic progenitor cells (HPC) from patients with PV in vitro. The data presented confirm previous research which has shown an inhibitory effect of IFN-alpha on HPC from patients with myeloproliferative disorders. Significant improvement in the patients' clinical and haematological conditions should encourage larger studies on IFN-alpha administration in PV patients. PMID- 7993807 TI - Lymphoid blast crisis at the onset of chronic myelogenous leukaemia: molecular evidence. AB - A patient with a typical haematological pattern of acute lymphoblastic leukaemia with BCR and IgH rearrangements was brought into complete remission by treatment. A few weeks later she developed the typical peripheral and bone marrow pattern of chronic myelogenous leukaemia (CML) with persistence of the BCR rearrangement and disappearance of the IgH rearrangement, suggesting that this case is an example of CML presenting in blast crisis without a detectable chronic phase. PMID- 7993809 TI - The effects of gestation on circulating progenitor cells. AB - The frequency of BFU-E in second-trimester fetal blood (484 +/- 104/10(5)) falls progressively during gestation to a value of 69 +/- 41/10(5) in cord bloods of 36 weeks gestation and beyond, but this is still significantly greater than adult blood values of 14 +/- 8 (P < 0.01). BFU-E obtained from unfractionated peripheral blood mononuclear cells from fetuses/neonates less than 36 weeks gestation were more sensitive to erythropoietin than adult BFU-E, but the sensitivity of highly purified BFU-E obtained from second-trimester fetal liver was similar to that in adult cells. Almost maximal growth of BFU-E from purified fetal progenitor cells could be achieved with erythropoietin alone, whereas adult cells required the presence of other factors with 'burst-promoting activity'. PMID- 7993808 TI - Sequential relapses of blastic crisis may involve different clones of cells with different molecular abnormalities. AB - A patient with typical Ph1-positive CML was studied during sequential phases: (1) initial chronic phase, (2) first myeloid blast crisis, (3) second chronic phase, and (4) accelerated disease leading to a second blast crisis. A point mutation in codon 239 of the p53 gene and a novel chromosome 17 alteration appeared concomitantly with the first blast crisis and then disappeared with re establishment of a second chronic phase. They did not reappear with the second acute phase, indicating that the clone responsible for the original blast crisis had been suppressed and supplanted by another clone of malignant cells. This observation suggests that in at least some CML patients drug therapy can suppress or eliminate an aggressive malignant cell clone, but that the underlying molecular defect in haemopoietic cells (in this case the c-ABL translocation) persists and other aggressive clones with different molecular lesions eventually arise. Our observations and inferences are consistent with the hypothesis advanced by Fialkow et al (1991) to explain clonal remissions in acute non lymphocytic leukaemia. PMID- 7993810 TI - Significant amount of hepatocyte growth factor detected in blood and bone marrow plasma of leukaemia patients. AB - Hepatocyte growth factor (HGF) has been known as a versatile functional molecule, and as being involved in the colony formation of haemopoietic progenitor cells. Clinically, an elevated HGF level in the blood has been associated with liver diseases such as fulminant hepatic failure and acute hepatitis. We have found a high level of HGF in blood and bone marrow plasma from patients with various types of leukaemia and lymphoma. In particular, 21/31 acute myeloblastic leukaemia (AML) patients showed a significant level of HGF (> 0.40 ng/ml) in their blood or bone marrow plasma. The mean value of HGF in the plasma of AML patients was 2.03 ng/ml, which was higher than that in the serum of patients with acute hepatitis. This demonstrates, for the first time, evidence of frequent association of increased levels of HGF in non-lymphocytic leukaemias, though its significance in the disease remains unknown. PMID- 7993811 TI - Elevated levels of soluble factors in the cerebrospinal fluid in patients with adult T-cell leukaemia complicated with meningeal infiltration. AB - We measured some soluble factors in the cerebrospinal fluid (CSF) of patients with adult T-cell leukaemia (ATL) complicated with meningeal infiltration. Interleukin-4 (IL-4) was not detectable in the CSF of all cases with meningeal infiltration. Interleukin-6 (IL-6) was detected in a few patients with ATL. Measurement of IL-4 and IL-6 in CSF had no diagnostic value for meningeal infiltration of ATL cells. Soluble CD4 (sCD4) was highly elevated in all ATL patients with meningeal infiltration. Soluble interleukin-2 receptor (sIL-2R; sCD25) in CSF was markedly elevated in 13/18 ATL patients (72.2%) with meningeal infiltration. Levels of sCD4 and sCD25 in the CSF of ATL patients with central nervous system (CNS) symptoms were significantly higher than those of non-ATL patients with CNS symptoms. These observations indicate that sCD4 and sCD25 in the CSF are probably associated with meningeal infiltration of leukaemia cells that expressed CD4 and CD25 on the surface membrane and new markers for the meningeal infiltration of ATL cells. PMID- 7993813 TI - A new type of pseudothrombocytopenia: EDTA-mediated agglutination of platelets bearing Fab fragments of a chimaeric antibody. AB - In vitro agglutination of platelets leading to low automated platelet counts was observed in EDTA-anticoagulated blood from human volunteers receiving infusions of Fab fragments of a chimaeric monoclonal antibody to platelet glycoprotein IIb IIIa. This pseudothrombocytopenia depended on the presence of chimaeric Fab on the platelet surface and was not seen when sodium citrate was used as anticoagulent. Preliminary evidence suggests that this phenomenon might be mediated by immunoglobulin G reactive with the human component of the chimaeric Fab. It is important to exclude pseudothrombocytopenia when low automated platelet counts are reported in association with the administration of chimaeric anti-platelet antibodies. PMID- 7993812 TI - Detection and significance of bone marrow infiltration at the time of autologous bone marrow transplantation in Hodgkin's disease. AB - Bilateral iliac crest biopsies were performed at the time of bone marrow (BM) harvest in patients with poor-risk Hodgkin's disease (HD) undergoing autologous bone marrow transplantation (ABMT). 67 consecutive patients with normal trephine biopsies (58 unilateral; nine bilateral) taken 2 weeks prior to harvest were studied. Nine (13%) of patients had BM infiltration with HD on the harvest biopsies. These patients had all previously had only unilateral biopsies. Three patients did not proceed to ABMT because disease progression became clinically apparent, but the remaining six patients were infused with involved marrow. One patient died 6 weeks post ABMT, with no evidence of disease at post-mortem. One patient showed no response to ABMT and four patients either had a partial or complete response to ABMT. Of the responders, three patients are now in complete remission at 53, 39 and 33 months past ABMT. PMID- 7993814 TI - Serum thymidine kinase in congenital dyserythropoietic anaemia type III. AB - Serum thymidine kinase (TK) was determined in a family with congenital dyserythropoietic anaemia type III (CDA, type III). 20 patients and 10 of their healthy siblings were investigated. Elevated TK was found in all 20 patients (median 56.2 U) but their healthy siblings had normal values (median 2.65 U). We suggest that determination of TK should be used for discrimination between healthy siblings and individuals affected by CDA type III when bone marrow examination is not suitable. PMID- 7993815 TI - A function of CD10 on bone marrow stroma. AB - Bone marrow (BM) stromal cells express CD10 (cALLA), a surface antigen now known to be a neutral endopeptidase (NEP-24.11). The function of CD10 in BM stroma is unknown, although purified NEP-24.11 is known to degrade different substrates including interleukin 1 beta (IL-1 beta). We have therefore employed a CD10 positive BM stromal cell line (L2AK) which proliferates in response to IL-1 beta to test the hypothesis that degradation of this cytokine is one of the functions of stromal CD10. We first showed that [3H]thymidine incorporation by L2AK cells is enhanced by IL-1 beta in a clear dose-dependent manner. Addition of the CD10 inhibitor, phosphoramidon, together with IL-1 beta resulted in a left shift in the dose-response curve which corresponded to a 10-fold potentiation of the IL-1 beta effect. These results indicate that CD10 on bone marrow stromal cells can degrade IL-1 beta and therefore provide a local control of the effects of this, and possibly other, growth factor(s). PMID- 7993816 TI - Detection of fetal RhD sequence from peripheral blood of sensitized RhD-negative pregnant women. AB - A sensitive PCR-based assay was developed to amplify fetal-derived rhesus D (RhD) sequence from peripheral blood of RhD-negative pregnant women with circulating anti-D. RhD-PCR positivity was detected in 7/22 samples from women bearing RhD positive fetuses, despite the presence of varying levels of anti-D. Evidence is presented which suggests that rising maternal anti-D levels might reduce circulating fetal cell numbers. Further development of this assay may have implications in the clinical management of RhD-sensitized pregnancies and aid the understanding of the physiology of feto-maternal cell trafficking. PMID- 7993817 TI - Splenectomy for treatment of immunoblastic lymphadenopathy. AB - A 5-month-old girl was diagnosed with immunoblastic lymphadenopathy (IBL) on the basis of clinical symptoms and pathological findings. alpha-interferon, immunosuppressive agents such as cyclosporin A, deoxyspagarine, and azathioprine, and an alternating regimen of low-dose 6-mercaptopurine, cyclophosphamide and methotrexate were tried with partial success. Finally, splenectomy was carried out at 58 months of age, inducing prolonged complete remission without any medication. PMID- 7993818 TI - A patient with multiple myeloma and respiratory insufficiency due to accumulation of paraprotein in the alveolar space. AB - We describe a patient with multiple myeloma and respiratory insufficiency. Autopsy revealed accumulation of IgG-kappa paraprotein in the alveolar space. The clinical and pathological presentation are typical for secondary pulmonary alveolar proteinosis. Attention is focussed on the possibility of secondary pulmonary alveolar proteinosis as a cause for dyspnoea in patients with haematological malignancies. PMID- 7993819 TI - Should all pregnant women be tested for their platelet PLA (Zw,HPA-1) phenotype? PMID- 7993820 TI - Should all pregnant women be tested for their platelet PLA (Zw,HPA-1) phenotype? PMID- 7993821 TI - Plasma viscosity and erythrocyte sedimentation rate in suspected cases of temporal arteritis. PMID- 7993822 TI - The value of DNA image cytometry for the cytological diagnosis of well differentiated breast carcinomas and benign lesions. AB - Cytological evaluation of breast diseases can lead to false diagnosis if benign lesions show epithelial atypia or if carcinomas are orthoplasic and well differentiated. In order to determine the potential usefulness of image cytometry for discrimination between benign and malignant breast lesions, we studied 120 Feulgen-stained imprints, half from benign lesions with epithelial atypia and half from well-differentiated carcinomas and determined values of parameters expressing DNA content, morphometry and chromatin texture. Twenty-five out of the 60 carcinoma imprints were found to be DNA-aneuploid and could thus be easily distinguished from benign imprints, as, in our and other authors' experiences, aneuploidy very rarely occurs in benign breast lesions. When the remaining 35 carcinoma imprints were compared with 38 benign lesion imprints, randomly selected from the 60 cases studied, only four cases were misclassified after a linear discriminant analysis; the most discriminant parameters were those expressing the heterogeneity of DNA content and the chromatin texture. Thus, in cases where cytological diagnosis is difficult, image analysis of Feulgen-stained imprints may be a very useful tool for correctly discriminating benign from malignant cases. PMID- 7993823 TI - Assessment of proliferative activity in Wilms' tumour. AB - The proliferative activity in 26 cases of Wilms' tumour was studied by enumeration of silver-staining nucleolar organizer regions (AgNORs) and proliferating cell nuclear antigen (PCNA) staining of the blastemal, epithelial and stromal components of the tumours. The PCNA and AgNOR scores derived from the blastemal (PCNA range 18.9-81.4%, AgNOR range 2.11-4.95) and epithelial (PCNA range 24.1-74.2%, AgNOR range 2.47-4.41) components of the tumours were significantly higher than those of the stromal component (PCNA range 3.4-64.7%, AgNOR range 2.20-4.26). Ten of the patients had died with recurrent or metastatic tumour (mean survival 29 months) while the remaining 16 were disease free (mean follow-up 95 months) at the time of the study. The prognostic significance of PCNA and AgNOR for Wilms' tumour was evaluated by dividing the tumours into groups exhibiting low (PCNA < or = 40 or AgNOR < or = 4) or high (PCNA > 40 or AgNOR > 4) proliferative activity. There was a significant difference in the survival of the two groups for tumours treated with preoperative chemotherapy (PCNA, P = 0.049; AgNOR, P = 0.02), while no significant difference was observed from tumours resected prior to the administration of chemotherapy. The results of this study suggest that assessment of proliferation activity in postchemotherapy Wilm's tumours may be a useful indicator of prognosis. PMID- 7993824 TI - High resolution image-cytometric differentiation of hormone sensitive and hormone insensitive prostatic carcinomas. AB - Until the present it was not possible to predict hormone sensitivity of prostatic carcinoma. Based on studies correlating image cytometric results of hormone receptor negative and hormone receptor positive breast carcinomas, the present study aims at separating responders and non-responders to hormone therapy in metastatic prostatic carcinoma. From May-Grunwald-Giemsa stained slides of fine needle aspirates of 23 patients with metastasizing prostatic carcinoma about 100 nuclei per slide were taken by TV camera for image-cytometric processing. One thousand and twenty-two nuclei came from 10 patients who showed tumour regression for at least 36 months and who all survived for more than 5 years. One thousand three hundred and thirty-two nuclei were from prostatic aspirates of patients who showed a continuous tumour progression despite receiving hormone therapy. All patients of the latter group died within 5 years. A correct classification of the patient groups of responders and non-responders was possible in 19-21 of 23 cases by means of high resolution image analysis including nuclear structural features. It was found that even simple planimetric features, like the nuclear perimeter, or densitometric features, such as the total nuclear extinction, differed markedly between the two groups. The data show that nuclei from hormone sensitive prostatic carcinoma are distinct from those of non-sensitive ones in the present series. The interpretation of results must take into account that the very strict criteria for hormone sensitivity leads to a highly selected patient group. The application of the method to an unselected patient group can be presumed to yield a higher rate of false classifications. PMID- 7993825 TI - Karyometric analysis of intra-tumour heterogeneity in prostate adenocarcinoma. AB - The intra-tumour heterogeneity in different locations in the prostate was determined by karyometric image analysis and compared with local tumour progression in a retrospective analysis of 65 patients with localized adenocarcinoma of the prostate. In these 65 radical prostatectomy specimens 290 tumour locations were documented. In each location tumour volume was estimated and Gleason grade determined. Quantitative image analysis of nuclear size, shape and chromatin pattern was performed. Differences in Gleason grade and karyometric feature values were evaluated as measures for intra-tumour heterogeneity. Moreover, the location within the prostate was documented for each tumour area. Gleason grade and karyometric features varied widely in the prostate. Tumour locations in the apex (n = 92) had significantly larger and more irregularly shaped nuclei (P < 0.005) compared with basally located tumours (n = 49). Significant differences in nuclear shape were also found in different locations in the equatorial plane of the organ. Tumour heterogeneity in chromatin pattern features was found to correlate with local extension (seminal vesical invasion, extracapsular tumour growth, positive resection margins) and lymph node metastases. This correlation was even stronger when more pathological features were present. In view of the observed tumour heterogeneity, (karyometric) analysis of multiple tumour areas in the prostate is advisable for optimal evaluation of prostate carcinoma. PMID- 7993826 TI - Pattern interpretation by cellular automata (PICA)--evaluation of tumour cell adhesion in human melanomas. AB - In routine pathology, the evaluation of the pattern of a tumour at scanning magnification often reveals diagnostic and prognostic features indicating that the biological properties of the tumour cells are related to the morphological pattern. For further evaluation of the relationship between functional properties of the cells on the one hand and the pattern on the other, we propose the pattern interpretation by cellular automata (PICA) procedure. The PICA system consists of an import module transferring real histological images into the data structure of a cellular automaton, a measurement module generating a comparable quantitative description of real and simulated images, a cellular automation designed to simulate tumour growth and invasion at the histological level, a database consisting of the morphological results obtained in simulated patterns, an interpretation module linking real histological images to the knowledge stored in the database and an image synthesis and display module. By comparing real images to computer-simulated patterns, PICA facilitates an estimation of functional properties based on the static histological pattern of a given tumour. Using the example of tumour cell adhesion, it is demonstrated that the degrees of tumour tumour and tumour-stroma adhesion significantly affect the resulting simulated patterns, that, in turn, the morphological evaluation of the patterns enables a reproducible estimation of adhesion and that estimates of adhesion in real images of malignant melanoma of the skin are of prognostic significance. PICA may serve as an additional in situ evaluation technique linking morphological features to functional properties. PMID- 7993827 TI - Scientists find genes for colorectal cancer, raising hopes for genetic test. PMID- 7993828 TI - New directions for anti-emetic research. PMID- 7993829 TI - Chemoprophylaxis of fungal infections in neutropenic patients. AB - BACKGROUND: In recent years there has been an increasing incidence and awareness of mucosal candidiasis and invasive fungal infections in neutropenic patients. Early diagnosis (before serious morbidity and mortality) is often difficult, emphasizing the continuing need for adequate prophylaxis. DESIGN: A review of studies on the chemoprophylaxis of fungal infections in neutropenic patients. RESULTS: There is a limited number of large, prospective, well-designed studies using proper criteria and end points. No antifungal drug or drug combination has been shown to prevent invasive fungal infection with the exception of fluconazole (mainly Candida Albicans infections) in certain high-risk patients groups. CONCLUSIONS: Prophylaxis strategies are dependent upon local conditions, patient populations, types of therapies, available resources, etc. Future improvement will be based upon a) improved study quality, b) new strategies for established drugs, c) development of new and safer drugs, d) new strategies to eliminate or reduce immunosuppression and e) cost-benefit studies. PMID- 7993830 TI - Special conference on 'growth factors, development and cancer. PMID- 7993831 TI - Oral granisetron alone and in combination with dexamethasone: a double-blind randomized comparison against high-dose metoclopramide plus dexamethasone in prevention of cisplatin-induced emesis. The Granisetron Study Group. AB - PATIENTS AND METHODS: Three anti-emetic treatment regimens were compared in 357 patients receiving cisplatin therapy (mean dose 81 mg/m2) in this double-blind randomized study. Regimens studied were i) granisetron 1 mg bd orally for 7 days (granisetron alone); ii) gran 1 mg bd orally for 7 days plus prophylactic dexamethasone (12 mg i.v.) on the first day only (gran/dex); iii) metoclopramide (3 mg/kg i.v. loading dose; 4 mg/kg i.v. infusion) plus dex (12 mg i.v.) on the first day followed by met 10 mg orally tds for a further 6 days (met/dex). RESULTS: At 24 hours, gran/dex was significantly superior to met/dex in terms of total anti-emetic control, defined as no nausea, no vomiting, no rescue anti emetic therapy, not withdrawn (54.7% gran/dex vs. 37.2% met/dex; P < 0.01). There was also a significant delay in time to onset of nausea (P < 0.01) and vomiting (P < 0.01) following gran/dex compared with met/dex. Oral granisetron alone was as effective as met/dex in control of acute emesis in all parameters examined. There were no significant differences between the three groups in the control of delayed nausea and vomiting. The most common adverse experiences in both granisetron groups were headache and constipation, both characteristic of 5-HT3 antagonists. Agitation, somnolence, diarrhoea and decreased appetite were reported more frequently by the met/dex group. CONCLUSIONS: Oral granisetron as a single agent is as effective as high doses of i.v. met/dex in preventing cisplatin-induced emesis. Oral granisetron in combination with a corticosteroid provides superior anti-emetic control to the met/dex regimen in patients undergoing highly emetogenic chemotherapy. PMID- 7993832 TI - Cisplatin-induced delayed emesis: pattern and prognostic factors during three subsequent cycles. Italian Group for Antiemetic Research. AB - BACKGROUND: Cisplatin-induced delayed emesis has been studied much less than has acute emesis. In particular, its pattern of presentation and prognostic factors have not been evaluated in a large enough patient population submitted to multiple cycles of chemotherapy. PATIENTS AND METHODS: Delayed nausea and vomiting occurring in patients submitted to cisplatin (> or = 50 mg/m2) chemotherapy were analyzed for three consecutive cycles. All patients were treated with the same antiemetic therapy (i.m. dexamethasone and oral metoclopramide) for delayed emesis, while they had received either i.v. ondansetron plus dexamethasone or metoclopramide plus dexamethasone plus diphenhydramine for acute emesis. RESULTS: Two hundred forty-nine patients were evaluable at first cycle of chemotherapy, 195 at second and 163 at third. About 25%-30% of patients presented delayed vomiting, 40%-45% nausea and 45%-50% nausea and/or vomiting. The percentage of patients suffering from delayed emesis remained similar in the three cycles of chemotherapy. Dose of cisplatin, control of acute emesis and dependence effect from the results obtained in the control of acute and delayed emesis of the previous cycle were found to be the most important prognostic factors of delayed emesis. Adverse events were infrequent and mild. Hiccup was significantly more frequent in patients receiving high-dose metoclopramide. CONCLUSIONS: Despite the use of the most efficacious antiemetic treatment, delayed emesis remains an unsolved problem in cisplatin-treated patients. Efforts should be directed to obtain better control of acute and delayed emesis, since they have a mutual influence. PMID- 7993833 TI - Primary (neoadjuvant) chemotherapy and radiotherapy compared with primary radiotherapy alone in stage IIb-IIIa breast cancer. AB - BACKGROUND: A phase III randomized trial was activated to evaluate the efficacy of preoperative combined chemotherapy and radiotherapy as compared to preoperative radiation therapy alone, in patients with breast cancer presenting with a clinical stage of IIb-IIIa (TNM classification). PATIENTS AND METHODS: From 1985 to 1990, 271 patients, aged 27-55 years, with stage IIb-IIIa breast cancer were randomized to receive either one or two courses of thiotepa 20 mg (i.m. injection) on the days 1, 3, 5, 7, 9, 11 (total dose per course 120 mg), methotrexate 40 mg/m2, i.v. on days 1 and 8, and 5-fluorouracil 500 mg/m2, i.v. on days 1 and 8 (TMF regimen) plus radiotherapy (Group I, 137 patients), or preoperative radiation therapy only (Group II, 134 patients). After the preoperative treatment all patients underwent mastectomy and complete axillary clearance, and then received 4-6 courses of TMF. The trial was conducted in a single institution (N.N. Petrov Research Institute of Oncology, St. Petersburg). RESULTS: Histopathological assessment of the mastectomy specimens showed complete regression of the tumour in 29.1% of the patients in group I and in 19.4% of the patients e.c. in group II. The estimated 5-year overall survival percentages were 86.1% for group I, and 78.3% for group II (P > 0.05). 5-year disease-free survival percentages were 81.0% and 71.6%, respectively (p < 0.05). CONCLUSIONS: Despite the low number of the patients included in the trial, we were able to detect a significant improvement in treatment results with a combination of chemotherapy and radiation therapy given prior to mastectomy over those of local therapy alone with radiation therapy followed by mastectomy, for average- and high-risk patients with operable breast cancer. PMID- 7993834 TI - Suramin for breast and prostate cancer: a pilot study of intermittent short infusions without adaptive control. AB - BACKGROUND: Suramin has shown promising activity against prostate and breast cancer but is severely neurotoxic. Complex adaptive pharmacokinetics have previously been used to adjust doses. We have undertaken a pilot study to assess the feasibility of administering suramin to outpatients with advanced cancer, using simple peak and trough monitoring. PATIENTS AND METHODS: Nine patients with cancer refractory to conventional therapy were studied, eight with breast cancer and one with prostate cancer. Two received continuous infusions of suramin 350 mg/m2/day through an indwelling central venous catheter. Both sustained axillary vein thromboses. Subsequent patients received suramin 500 mg/m2 as a one hour intravenous infusion thrice weekly until a trough serum level of 200 micrograms/ml was achieved. Treatment was repeated at 8 week intervals. Serum suramin levels were checked before and after each dose. RESULTS: Suramin treatment was well tolerated. Despite peak serum levels of up to 506 micrograms/ml, no serious toxicity was seen. No tumour responses were seen. CONCLUSIONS: We conclude that suramin can be safely and conveniently administered to outpatients by intermittent infusion without using complex adaptive dosing strategies. Suramin merits further study in less heavily pretreated breast cancer patients. PMID- 7993835 TI - Randomized comparison of etoposide-cisplatin vs. etoposide-carboplatin and irradiation in small-cell lung cancer. A Hellenic Co-operative Oncology Group study. AB - PURPOSE: To compare the efficacy and toxicity of etoposide and cisplatin (EP) with etoposide and carboplatin (EC) in combination with irradiation in small-cell lung cancer (SCLC). METHODS: Previously untreated patients (pts) with SCLC and measurable or evaluable disease were randomized to receive either cisplatin 50 mg/m2 on days 1-2 or carboplatin 300 mg/m2 on day 1, both combined with etoposide 300 mg/m2 on days 1-3 every 21 days for 6 treatment cycles. The vast majority of responding limited disease (LD) pts and complete responders (CR) with extensive disease (ED), also received thoracic irradiation (TI) and prophylactic cranial irradiation (PCI) concurrently with the third cycle. RESULTS: Of the 147 patients registered, 143 were eligible; median performance status (PS, WHO) was 1, and tumour stage was LD in 41 pts of each treatment group. The mean delay between cycles was 8 days in the EP group and 9 in the EC group increasing in both arms with the number of treatment courses. The drug dose administered per unit time as a proportion of the protocol dose was 74% and 80% for the two groups respectively. Leukopenia, neutropenic infections, nausea, vomiting, neurotoxicity and hyperergic reactions were more frequent and/or severe in the EP group. The CR rates were 57% and 58% for EP and EC respectively. Median survival for all pts was 12.5 and 11.8 months, respectively. CONCLUSION: Both treatments proved to be effective, with no differences in response and survival between the two treatment arms. The EC regimen was associated with significantly less toxicity. PMID- 7993837 TI - Usefulness of indium-111 antimyosin scintigraphy in confirming myocardial injury in patients with anthracycline-associated left ventricular dysfunction. AB - BACKGROUND: In patients with cardiac dysfunction due to anthracycline-induced myocyte damage, continuation of anthracyclines carries a high risk, and modification of chemotherapy is thus indicated. The condition, however, must be distinguished from other causes of cardiac dysfunction, e.g., the transient negative inotropic effect which may accompany and follow the intravenous administration of anthracyclines. In the present study the efficacy of 111In antimyosin in confirming myocyte injury and its potential applicability in differentiating causes of cardiac dysfunction during anthracycline therapy are evaluated. PATIENTS AND METHODS: Twenty-seven patients with asymptomatic left ventricle ejection fraction (LVEF) decrease (median LVEF 47%, range 38%-50%) during chemotherapy with anthracyclines (dose range 100-700 mg/m2 doxorubicin or equivalent) were subsequently studied with 111In-antimyosin cardiac scintigraphy. The degree of myocardial uptake, an indicator of heart muscle cell injury, evaluated both visually and quantitatively by means of heart-to-lung ratios (HLR) obtained from 48-hour planar images, was analyzed in relation to the further clinical and LVEF course. The results were also compared with 111In-antimyosin data from 5 patients who had normal LVEF during chemotherapy and 5 patients who had received no anthracyclines. The distribution pattern of myocardial uptake was assessed by means of single photon emission computed tomography (SPECT). RESULTS: a) Fourteen patients presented with persistent LVEF decrease (median LVEF 42.5%, range 32%-47%) after discontinuation of anthracycline therapy. In 11 of these patients intense and diffuse, as shown by SPECT, cardiac uptake of 111In antimyosin (HLR 1.87-2.45) was observed. In two patients with intense antimyosin cardiac uptake, spurious HLR values (1.23-1.55) were found which were caused by unexpected lung uptake and focal heart uptake, respectively. All patients with intense cardiac 111In-antimyosin uptake showed persistently decreased LVEF on follow-up (4-26 weeks) and 4 of them subsequently developed congestive heart failure. In another patient with no intense uptake (HLR 1.15) and persistent decrease in LVEF, metastatic cardiac involvement was found. b) In 13 patients with improvement or normalisation of the LVEF (median LVEF 53%, range 51%-63%), generally less intense or slight cardiac uptake (HLR range: 1.20-1.88) was seen; the HLR in these patients, who continued chemotherapy without complications, was consistently lower (p < 0.01) than in patients with persistently decreased LVEF, and comparable to values of patients who had normal LVEF. CONCLUSIONS: 111In antimyosin scintigraphy can be useful to differentiate cardiac dysfunction caused by severe myocardial injury from temporary decreases in LVEF, without severe concomitant myocyte damage, which may occur during anthracycline therapy. Intense myocardial uptake of 111In-antimyosin can be used as an important confirmatory criterium for the clinical decision to discontinue anthracycline therapy. PMID- 7993836 TI - A phase II study in advanced gastro-esophageal cancer using epirubicin and cisplatin in combination with continuous infusion 5-fluorouracil (ECF). AB - PURPOSE: A phase II study was performed in patients with unresectable or metastatic gastric cancer evaluating the efficacy of a new chemotherapy schedule combining epirubicin and cisplatin with a continuous ambulatory infusion of 5 fluorouracil (ECF). PATIENTS AND METHODS: One hundred thirty-nine consecutive, previously untreated patients were given ECF. Of these, 128 had measurable disease. Epirubicin (50 mg/m2 i.v.) and cisplatin (60 mg/m2 i.v.) were administered every three weeks for 8 cycles during a 21 week continuous i.v. infusion of 5-fluorouracil (200 mg/m2/day). In total 773 cycles of chemotherapy were given. RESULTS: Objective tumour responses was seen in 91 (71%) of the 128 patients with measurable disease, of which 15 (12%) had a complete response. Twenty patients with locally advanced disease responding to ECF had attempted resection of the primary--11 (55%) were completely removed, 4 of these had no residual tumour in the resected specimen. The overall median survival was 8.2 months with 1 and 2 year survivals of 30% and 10% respectively. Grade 3 or 4 emesis occurred in 13%, stomatitis in 7%, diarrhoea in 4%, infection in 6%, leucopenia in 21% and thrombocytopenia in 8% of patients. Myelosuppression delayed treatment in 39 (5%) of the 773 cycles. Six of the 139 patients (4.3%) had treatment related deaths. There was no measurable reduction in quality of life during chemotherapy, while 67% of the 66 patients with dysphagia had complete resolution of this symptom. CONCLUSIONS: The ECF regimen displays high anti-tumour activity with moderate toxicity in patients with gastric cancer and in some cases enabled resection of previously inoperable tumours. PMID- 7993838 TI - Fucosyl-GM1 in small-cell lung cancer. A comparison with the tumour marker neuron specific enolase. AB - BACKGROUND: Recently, the ganglioside Fucosyl-GM1 (FucGM1) has been described as a possible new tumour marker for small-cell lung cancer (SCLC). FucGM1 has been detected in 75% to 90% of SCLC tumours by immunohistochemical analysis and in about 50% of sera from SCLC patients. Neuron-specific enolase (NSE) is a glycolytic enzyme which is expressed in the majority of SCLC tumours and patient sera. PATIENTS AND METHODS: Sera from 156 patients with SCLC were analyzed for FucGM1 with a scintillation proximity assay (SPA), which is a simple and sensitive analysis. Sera were analyzed before the initiation of chemotherapy, and twenty patients were monitored during and after treatment. The concentration of FucGM1 was compared to the tumour marker NSE and related to clinical data and survival. RESULTS: Sixty-three per cent of the patients were positive for FucGM1. The concentrations did not correlate with NSE or clinical data including stage of disease, organ site of metastases or ABO blood group status. Nor did the expression of FucGM1 correlate with survival. As a monitor of clinical response, a correlation was found in 8 out of 20 patients. Eighty-four per cent of the patients were positive for NSE; and 97% were positive for either FucGM1 or NSE. CONCLUSION: We conclude that FucGM1 does not have a clinical role as a tumour marker for patients with SCLC at diagnosis or during treatment. PMID- 7993839 TI - Cell kinetics of human ovarian cancer with in vivo administration of bromodeoxyuridine. AB - BACKGROUND: Cell kinetics could have prognostic significance in human ovarian cancer and might also help in designing optimal therapy. No data are available on the in vivo kinetics of this tumor using bromodeoxyuridine (BrdU) infusion before surgery. PATIENTS AND METHODS: The kinetic parameters of human ovarian carcinoma were investigated in vivo using BrdU incorporation and bivariate BrdU/DNA flow cytometric (FCM) analysis. Fifty-five previously untreated patients with ovarian cancer (F.I.G.O. clinical stage III and IV) were studied. BrdU (250 mg/sqm) was given i.v. 6 h before surgery and samples of primary tumor and metastasis biopsies were fixed in 70% ethanol. By coupling the BrdU immunoreaction with biparametric FCM analysis, the nuclear DNA content (i.e., ploidy status), the tumor labelling index (LI), the synthesis time (TS) and the potential doubling time of the tumor mass (Tpot) were obtained. BrdU immunodetection was done on histological sections of the same tumors. RESULTS: The majority of the tumors had a DNA aneuploid content (71.5%). The amount of BrdU-positive S-phase cells varied in different tumor samples and when several samples were taken from the same tumor. The proportion of BrdU-negative S-phase cells was large (50% of the total S phase cells) in almost all cases. The mean LI was 6.1% using FCM and 7.2% on visual count of the slide. The mean TS and Tpot were 14.7 h and 12.5 days, respectively. LI and TS were not correlated with clinical tumor stage, histological grading, residual tumor size or DNA ploidy, but Tpot was significantly higher (p < 0.05) in patients with residual tumor size < 2 cm. Univariate analysis showed that Tpot was significantly associated with the response after first-line chemotherapy (p < 0.009). In multivariate analysis only residual tumor size was related to the response. CONCLUSION: Although this in vivo BrdU technique provides information on the kinetic features of human ovarian cancers, it remains questionable whether this information has any additional value compared to currently used prognostic factors which are assessable clinically and surgically. PMID- 7993840 TI - Management of advanced colorectal cancer. PMID- 7993841 TI - A four-drug combination chemotherapy with cisplatin, mitomycin, vindesine and 5 fluorouracil. A regimen associated with major toxicity in patients with advanced non-small lung cancer. European Lung Cancer Working Party. AB - PURPOSE: To determine in patients with advanced non-small cell lung cancer the activity of a 4-drug combination chemotherapy. PATIENTS AND METHODS: Chemotherapy consisted of the administration of cisplatin (30 mg/m2 d 1-3 or 4), mitomycin C (10 mg/m2 d 1), vindesine (3 mg/m2 d 1) and 5-FU (1 g/m2 d 1-3 or 4 by continuous intravenous infusion. RESULTS: 182 were eligible patients. A 34% objective response rate was observed in the 164 evaluable patients. The overall median survival was 26 weeks. The most serious adverse event was the occurrence of 18 (10%) cardiac or sudden deaths. These toxic deaths were significantly associated with a > or = 5% loss of body weight prior to therapy. CONCLUSIONS: The regimen studied resulted in a very significant cardiac toxicity. PMID- 7993842 TI - 5-fluorouracil and high dose folinic acid in hormone-refractory metastatic prostate cancer: a phase II study. AB - BACKGROUND: The response of hormone-refractory metastatic prostate cancer to chemotherapy is poor. The antitumour activity of single agent 5-fluorouracil (5 FU) is approximately 15%. Folinic acid is a reduced folate which when combined with 5-FU augments the activity of 5-FU by stabilizing the ternary complex of 5 deoxyuridine monophosphate-thymidylate synthetase-5,10 methylene tetrahydrofolate, resulting in increased DNA inhibition and in increased cytotoxicity of 5-FU. PATIENTS AND METHODS: We used the combination of 5-FU at 300-370 mg/m2 and folinic acid at 200 mg/m2 daily for five days in 16 patients with hormone-refractory metastatic prostate cancer. RESULTS: A total of 15 evaluable patients were treated. There were no complete or partial responses. Seven patients had stable disease. Diarrhea constituted the most common non hematologic toxicities (67%). Four patients experienced grade 3 and 4 neutrophil toxicity. There was one treatment-related death from an acute enterocolitis and peritonitis in a patient with grade 4 neutropenia. CONCLUSION: High dose folinic acid did not increase the cytotoxicity of 5-FU in hormone-refractory metastatic prostate cancer. PMID- 7993843 TI - Primary mediastinal germ cell tumour and acute monocytic leukaemia occurring concurrently in a 15-year-old boy. AB - This report describes the case of a 15-year-old boy who presented with a primary mediastinal germ cell tumour and while receiving chemotherapy developed an acute monocytic leukaemia. The occurrence of these conditions simultaneously is extremely rare, and the possible shared aetiology is discussed. Also, the role of the chromosome marker i(12p) in the diagnosis of germ cell tumours is examined. PMID- 7993846 TI - Association of acromegaly and two malignancies: colorectal cancer and non Hodgkin's lymphoma. PMID- 7993844 TI - A phase II trial of dose-escalated doxorubicin and ifosfamide/mesna in patients with malignant mesothelioma. AB - BACKGROUND: This study investigated the feasibility and efficacy of doxorubicin dose-escalated chemotherapy in combination with ifosfamide in patients with malignant mesothelioma. PATIENTS AND METHODS: In this single institution phase II study, 24 chemotherapy-naive, eligible patients were entered. The chemotherapy regimen consisted of doxorubicin 75 mg/m2 in combination with ifosfamide 5 gr/m2 given as a continuous 24 hour infusion, every 21 days with either rhG-CSF (5 micrograms/kg) or rhGM-CSF (250 micrograms/m2) as haematopoietic support from d3 to d14. Cycles were repeated every 3 weeks. RESULTS: We treated 24 patients, of whom 22 are evaluable for tumour response. One of the two inevaluable patients died from a cerebral haemorrhage during a period of grade III thrombocytopenia after the second course. In 7 patients a partial response was observed, resulting in a response rate of 32% (95% confidence interval 13%-51%). Median response duration was 6 months (range 1-13) and median survival was 7 months (range 1-18). CONCLUSIONS: The high-dose regimen with growth factor support is feasible in this group of patients and leads to an interesting response rate. The limiting toxicity for further dose increments and more courses of treatment, was cumulative thrombocytopenia. There seems to be a subgroup of patients with malignant mesothelioma which is less susceptible to develop thrombocytopenia. However, the overall toxicity and the poor response duration limit the use of this schedule in the treatment of malignant mesothelioma. PMID- 7993845 TI - Phase II study of prolonged oral etoposide in patients with ovarian cancer refractory to or relapsing within 12 months after platinum-containing chemotherapy. AB - PATIENTS AND METHODS: Twenty-eight patients with ovarian cancer refractory to or relapsing within 12 months after cisplatin-containing chemotherapy were treated with etoposide 50 mg/m2 daily for 21 days, followed by a 7-day break. RESULTS: Of 25 evaluable patients, 4 achieved partial responses (16%, 95% confidence interval 5%-36%) of 4, 4, 7, and 10 months' duration. The platinum treatment-free intervals for these patients were 2, 9, 7, and 10 months, respectively. Etoposide in this schedule was generally well tolerated, with myelosuppression as the major toxicity, resulting in a median dose intensity over all cycles of 83% (range 47% 100%). CONCLUSIONS: Prolonged oral etoposide is moderately active both in relapsed and platinum-refractory ovarian cancer, and a schedule of 50 mg/m2 days 1-21, every 4 weeks is fairly well tolerated in this usually heavily pretreated and elderly patient population. PMID- 7993847 TI - High dose oral amiodarone added to doxorubicin and vindesine for overcoming multidrug resistance in solid tumors. PMID- 7993848 TI - Meningeal and brain metastases in primary malignant pericardial mesothelioma. PMID- 7993849 TI - Breast cancer in a woman with HIV infection: a case report. PMID- 7993850 TI - More on intraperitoneal therapy. PMID- 7993851 TI - GM-CSF and dose escalation of chemotherapy. PMID- 7993853 TI - Rhythms in the central nervous system and 1/f fluctuations of the heart rate. AB - We have developed a system to analyze heart rate variability (HRV) (power spectral array of the HRV) during 24 h ambulatory electrocardiographic monitoring. Several rhythms (circadian and several ultradian rhythms) were observed in the power spectral array of the heart rates and 1/f-like fluctuations in the log-log scaled heart rate power spectrum. The circadian change of the heart rate is closely related to the body temperature rhythm. The 90 min rhythm of HRV during sleep was suspected to be produced by the sleep cycle (REM/NREM) and the lower frequency peak of the HRV was coherent with oscillation in amplitude modulated respiration. These circadian and ultradian rhythm as assessed by heart rate variability exist both in normal subjects and in patients with autonomic failure. The power of the high frequency band decreases in subjects with autonomic failure. The power of low frequency components increases during periodic breathing or Cheyne-Stokes respiration. Log-log scaled analysis of the power spectrum of HRV disclosed that the slope of the HRV is markedly modulated by the range of the frequency applied for the least square regression line analysis. The increased power that might be produced by periodic breathing and decreased power in patients with autonomic failure might strongly modulate the slope of the log-log scaled HRV. It is concluded that the power spectral array of the HRV during 24 h period is useful in the detection of circadian and ultradian rhythm, and log-log scaled power spectra might be useful in the overall integration of the heart rate dynamics produced by the central nervous system. The several rhythm factors that might be produced by the central nervous system might modulate 1/f fluctuations of the HRV. PMID- 7993854 TI - Estrous-related variations of blood pressure and heart rate in female rats. AB - In female rats, several biological variables change with a 4 or 5 day estrous cycle. To clarify whether blood pressure and heart rate show estrous-related changes, we measured three variables, i.e. mean arterial pressure (MAP), heart rate (HR) and spontaneous activity (ACT), using an implantable radiotelemetry transmitter and a computerized data collecting system non-invasively and chronically for more than 2 months. Under a 12-12 light-dark cycle, the three variables revealed clear daily variations and modulations by the estrous cycle which were most pronounced in the proestrous night. During the proestrous night, ACT showed a remarkable increase and a peak in the first half of the night, whereas MAP showed a gradual increase and a peak around midnight, and HR remained low without forming a peak. All modulations by the estrous cycle disappeared following bilateral ovariectomy. It is concluded that daily variations of blood pressure and heart rate are modulated according to the estrous cycle. PMID- 7993852 TI - Assessment of hypertension based on chronoengineering. AB - For the study of blood pressure, the use of automatic fully ambulatory recording systems greatly facilitates data collection and, in combination with proper software, the interpretation of results. Hardware for automatic long-term measurement is here wedded to a set of software modules to assess the circadian variability of human blood pressure. To evaluate changes in blood pressure within a day, the authors analyzed 303 series of systolic and diastolic blood pressures and heart rates automatically monitored every 30 minutes for at least 48 hours. Subjects were clinically healthy men and women, 19-23 years of age. Individual circadian rhythm parameters computed for each time series by least-squares rhythmometry were used, first, to assess rhythm characteristics of all subjects and for each gender separately, and, second, to compute a so-called paradesm, a (here 90%) time-specified prediction region for the amplitude-acrophase pair. The limits thus obtained for the circadian amplitude (an index of within-day variability) of blood pressure are exceeded in cases of amplitude-hypertension. Additionally, the original data were also used to compute time-specified tolerance limits for blood pressure and heart rate in clinical health. By the use of these reference standards many false positive and false negative diagnoses can be eliminated. Such reference limits may serve for an objective and positive definition of health, for the screening and diagnosis of disease, and for gauging a subject's response to treatment. The combined hardware-software method for the establishment of time-qualified tolerance limits presented allows the assessment of the extent and timing of rhythmic change and can be used for the interpretation of single values obtained at specified times. PMID- 7993855 TI - Issues and technology to assess circadian variability of blood pressure in hypertension. AB - Three problems remain to be solved to assess the circadian profile of blood pressure, and night dipper-non-dipper, day-night and morning rise of blood pressure in essential hypertension have been discussed. Both medical and bioengineering issues have been discussed to solve these important problems. PMID- 7993856 TI - Circadian profiles of blood pressure and heart rate of apparently healthy metropolitan Japanese. AB - The circadian waveform in blood pressure (BP) and heart rate (HR) was explored in metropolitan Japanese. Clinically healthy subjects (50 women and 50 men, aged 40 59 years) were selected for the study of computing a peer-group reference standard. Hypertensive subjects diagnosed by conventional criteria (systolic(S)BP/diastolic(D)BP > or = 160/90 mmHg) also volunteered for this study. Each was to provide measurements of SBP, DBP, and HR at 15 min intervals over 48 h by using an ambulatory monitor ABPM-630 (Colin Medical, Komaki, Japan). Reference limits were computed as 90% prediction limits specified by the circadian stage. Data in intervals of 30 min, displaced by 15 min, were used for the computation of these limits. Those time-qualified reference limits were reconstructed as 'three-component chronodesms' with the two harmonics (12 h and 8 h) in conjunction with the fundamental period (24 h). The coefficient of harmonics needed was determined by discrete Fourier transform (DFT). A diagnosis based on office BP readings was confirmed chronobiologically. As a result, the circadian BP profiles did not exceed the upper limit in 27/107 hypertensives for SBP and in 30/107 hypertensives for DBP. In conclusion, chronobiologic approaches improve the sensitivity and the reliability of diagnosis. PMID- 7993857 TI - Chronobioengineering toward a cost-effective quality health care. AB - The current disease-cure-oriented health care system does too little too late for too few. Engineering for concomitantly resolving the external conditions and the internal schedules, chronoengineering in the broad sense, could change this status quo into a system that recognizes environmental and organismic risk early, blows a whistle as a minimum and acts automatically, as an optimum. The chronobioengineering feature (of the broader chronoengineering for external as well as internal monitoring and decision helping) would gain new individualized information from the resolution of predictable variations that occur within the physiologic range, the chronomes, genetically anchored multifrequency rhythms and trends. Their resolution by chronobiometry provides a more precise and more accurate mean value (than the arithmetic mean) along with new dynamic endpoints for improved screening, diagnosis, prognosis, and timely and timed treatment. Trends are those with growth, development, maturation and aging, and also those with risk elevation or disease and treatment. Risk elevation may change amplitude or timing, but not necessarily the mean. The implementation of engineering for concomitantly resolving the external and internal schedules depends on telecommunications and telehygiene as well as telemedicine for (i) universal chronobiologic education (to assume self-responsibility and self-help in health care), (ii) physiologic monitoring (complemented as a sine qua non by chronobiologic data analysis and interpretation of the results) and (iii) the monitoring of pertinent environmental conditions. Thus, the number of cases of catastrophic diseases could be reduced and quality (since preventive) health care made available to all. PMID- 7993858 TI - Strategies for reducing blood transfusions in hepatic resection. AB - A comparison of 60 blood transfused and 71 nonblood transfused hepatic resection patients was done to evaluate strategies for reducing blood transfusions during hepatic surgery. There were no significant differences between the two groups with regard to preoperative laboratory data, except for prothrombin time and hematocrit value. The mean operative blood loss was 1990 ml and 760 ml in the blood transfused and nonblood transfused groups, respectively. A multivariate analysis suggested that the patient's body weight, preoperative prothrombin time, and operative blood loss independently predicted the need for intraoperative blood transfusion. Major postoperative complications developed more frequently in the blood transfused group than in the nonblood transfused group (31.7 vs. 11.3%, p < 0.005). These results suggest that the difference in operative blood loss between the two groups was related to the prolonged prothrombin time and a susceptibility for blood transfusion was found to exist particularly in patients with a lower hematocrit value as well as a lower body weight. Thus, the improvement of these preoperative laboratory data combined with avoiding the use of the hematocrit value as a determining factor for intraoperative transfusion could correspond to a reduction in operative blood loss, while curtailing the demands on blood bank facilities, and lowering the risk of postoperative complications. PMID- 7993859 TI - Intra-abdominal venous pressure during laparoscopic cholecystectomy. AB - Superior vena cava (SVC) and inferior vena cava (IVC) pressures were measured serially during laparoscopic cholecystectomy in which the intra-abdominal pressure was maintained at 12 mmHg. The influences of alteration of position from 15 degrees head-down to 15 degrees head-up and of the operative procedure of holding the gallbladder up to the right subphrenic space on SVC and IVC pressures were mild. IVC pressure was maintained almost equal to the intra-abdominal pressure during prolonged continuous pneumoperitoneum lasting longer than 60 min, while SVC pressure did not change significantly during operation. The discrepancy between SVC and IVC pressures underwent no change during continuous pneumoperitoneum. PMID- 7993860 TI - Complications after laparoscopic and conventional cholecystectomy: a comparative study. AB - The growing popularity of laparoscopic cholecystectomy (LC) has made extensive series comparing laparoscopic and conventional cholecystectomy in a prospective, randomized way nearly impossible. To evaluate LC we compared retrospectively 800 laparoscopic with 748 conventional cholecystectomies (CC). Of the 800 LC, 10 (1.2%) were converted to laparotomy. 6 conversions were related to aberrant anatomical features or features making dissection very difficult, 4 conversions were due to complications. There were 5 (0.6%) intraoperative complications during LC and 4 (0.5%) during CC. Postoperative morbidity was 2.1% (n = 17) after LC and 3.7% (n = 28) after CC. Particularly the incidence of wound problems was only 0.5% (n = 4) after LC while it was 1.3% (n = 10) after CC. Overall morbidity was 2.7% (n = 22) for LC and 4.2% (n = 32) for CC. Mortality rate after CC was 0.4% (n = 3), there were no deaths after LC. Common bile duct-injury rate was 0.2% (n = 2) for both groups. Complication rates after LC have been rapidly decreasing with growing experience. Laparoscopic cholecystectomy can safely be performed by appropriately trained surgeons in more than 90% of patients suffering from gallbladder disease. The low morbidity and mortality together with the significant advantages to patient recovery makes laparoscopic cholecystectomy the treatment of choice for symptomatic cholecystolithiasis. PMID- 7993862 TI - Solitary hepatic lymphangioma. A rare benign tumour: a case report. AB - Hepatic lymphangiomas are extremely rare; moreover cystic lymphangiomas usually arise in areas such as the neck and axilla, where loose connective tissue allows the expansion of lymphatic channels. The case of a 65-year old male is described, who presented with a solitary lymphangioma in the liver. The lesion was discovered incidentally and due to diagnostic uncertainty was removed surgically. A short review of histology, clinical presentation and preoperative diagnostic difficulties of hepatic lymphangiomas is given. PMID- 7993861 TI - The effect of communication between the right and left liver on the outcome of surgical drainage for jaundice due to malignant obstruction at the hilus of the liver. AB - Debate continues regarding the optimal management of irresectable malignant proximal biliary obstruction. Controversy exists concerning the ability of unilateral drainage to provide adequate biliary decompression with tumors that have occluded the communication between the right and left hepatic ductal systems. Between October 1986 and October 1989, 18 patients with malignant proximal biliary obstruction were treated by an intrahepatic biliary enteric bypass. Patients were divided into two groups based on the presence or absence of a communication between the right and left biliary systems. In Group I (n = 9), there was free communication; and in Group II (n = 9) there was no communication. There were two perioperative deaths (11%) one due to persistent cholangitis and the other to myocardial insufficiency both with one death in each group. The median survival (excluding perioperative deaths) was 5.6 months. Comparison of pre- and postoperative serum levels of bilirubin and alkaline phosphatase showed a significant decrease in each group, but no difference between the groups in the size of the reduction. Sixteen patients survived at least three months and the palliation was judged as excellent in eight, fair in five, and unchanged in three. These results demonstrate the effectiveness of biliary enteric bypass regardless of communication between the left and right biliary ductal systems. PMID- 7993863 TI - The influence of portal deviation on the effect of repeat dearterializations of a transplantable adenocarcinoma to the rat liver. AB - As liver tumours receive some of their blood supply from the portal vein, we wanted to illustrate the influence of portal blood flow in combination with dearterialization in the treatment of liver tumours. Forty male, inbred Wistar/Furth rats with an adenocarcinoma transplanted to the liver were treated with various inflow occlusions repeated daily for 5 days. Deviation of the portal blood flow alone with an end-side porto-caval shunt did not alter the tumour growth (p = 0.089). Thirty min of repeat dearterializations was potentiated by portal deviation so that tumour growth was delayed (p = 0.004). However, repeat dearterializations for 60 min in portal deviated rats induced irreversible liver damage and all rats died in a few days. Repeated dearterializations for 60 minutes alone retarded the tumour growth as efficiently (p = 0.007). Simultaneous occlusion of the hepatic artery and the portal vein for 30 minutes with a side side porto-caval shunted (total devascularization) did not affect tumour growth (p = 0.154). Liver aminotransferases (ASAT and ALAT) were substantially increased following dearterialization for 30 min in rats with either an end-side or a side side porto-caval shunt. Dearterialization for 60 min in rats with end-side porto caval shunts gave a further release of ASAT and ALAT. In conclusion, portal deviation did not augment the therapeutic benefit of repeat dearterializations for the treatment of this experimental liver tumour. Repeat dearterializations alone seemed to be a feasible and efficient therapy for liver tumours. PMID- 7993864 TI - Duodenal leiomyosarcoma mimicking a pancreatic pseudocyst. AB - A case of duodenal leiomyosarcoma presenting as a cystic mass is reported. Amylase, tumour markers levels in the cyst fluid and radiological findings suggested an inflammatory pancreatic pseudocyst. Exploratory laparotomy and frozen section examination showed a smooth muscle tumour of the duodenum. Pancreatoduodenectomy with pylorus-preser vation was performed and the patient remained symptom-free at 8 months follow-up. PMID- 7993865 TI - Solitary metastasis from cutaneous melanoma to the liver: resection by extended left hepatectomy (trisegmentectomy) with clearance of tumor from the portal vein. AB - A 61-year-old woman presented with low grade fever and an epigastric mass eight years following resection of a stage Clark IV infraclavicular cutaneous melanoma followed by axillary node dissection. Investigations revealed a tumor in segment II, III, IV and V of the liver and a thrombus involving the main portal vein. Liver resection with extended left hepatectomy (left trisegmentectomy) and portal vein thrombectomy is reported. PMID- 7993866 TI - Partial portacaval shunt: narrow diameter H-graft. PMID- 7993867 TI - Gastric varices: first you have to see them. PMID- 7993868 TI - Emergency portacaval shunts in variceal hemorrage: a critique of critics. PMID- 7993870 TI - Enucleation for giant liver haemangioma. PMID- 7993869 TI - The role of the distal splenorenal shunt in the sclerotherapy era? PMID- 7993871 TI - Acute variceal bleeding: somatostatin or sclerotherapy? PMID- 7993872 TI - Cystic lesions of the pancreas. PMID- 7993873 TI - Has propranolol rendered sclerotherapy obsolete for poor risk alcoholic cirrhotic patients? PMID- 7993874 TI - "Split" pancreaticojejunostomy in the surgical treatment of chronic pancreatitis. AB - "Split" pancreaticojejunostomy is a procedure consisting of vertical transection of the pancreas and anastomosis of both sides of the cut pancreatic duct with an interposed, Roux-en-Y jejunal loop. In this paper we report the long term results of this procedure in the treatment of eight patients with chronic pancreatitis (CP). PMID- 7993875 TI - Texture segmentation and 'pop-out' in infants and children: the effect of test field size. AB - The ability of infants and children to segment textures based on differences in line orientation and blob size was investigated, using a forced-choice preferential looking method. In the first experiment, a stimulus pair (a homogeneous texture and a texture containing either a group of sixteen elements or a single element of an orthogonal orientation or a larger blob size) was presented on two separate test fields. Preference for the figure defined by differences in blob size was seen already in 2-month-old infants. In contrast, preference for a figure defined by differences in orientation emerged at 9-12 months of age and became adult-like around school age (see also Sireteanu and Rieth, Behavioural Brain Res., 49, 133-139, 1992). Preference for the single discrepant element was always lower than preference for the discrepant group. In the second experiment, segmentation of oriented textures presented on a single, rather than two separate surfaces was tested. A significant preference for the embedded discrepant group, but not for the single discrepant element, was seen already at 3 months of age. These results show that infants as young as 3 months of age are able to detect a boundary defined by differences in line orientation (see also Atkinson and Braddick, Behavioural Brain Res., 49, 123-131, 1992). However, this ability does not appear to lead to the 'pop-out' phenomenon, as seen in adult observers, until much later. PMID- 7993876 TI - Attention and apparent motion. AB - Two dissociations between short- and long-range motion in visual search are reported. Previous research has shown parallel processing for short-range motion and apparently serial processing for long-range motion. This finding has been replicated and it has also been found that search for short-range targets can be impaired both by using bicontrast stimuli, and by prior adaptation to the target direction of motion. Neither factor impaired search in long-range motion displays. Adaptation actually facilitated search with long-range displays, which is attributed to response-level effects. A feature-integration account of apparent motion is proposed. In this theory, short-range motion depends on specialized motion feature detectors operating in parallel across the display, but subject to selective adaptation, whereas attention is needed to link successive elements when they appear at greater separations, or across opposite contrasts. PMID- 7993877 TI - Finding perceptually dominant orientations in natural textures. AB - An algorithm for detecting orientation in texture is developed and compared with results of humans detecting orientation in the same textures. The algorithm is based on the steerable filters of Freeman and Adelson (IEEE Trans. PAMI 13, 891 906, 1991), orientation-selective filters derived from derivatives of Gaussians. The filters are applied over multiple scales and their outputs non-linearly contrast-normalized. The data for humans were collected from forty subjects who were asked to identify 'the minimum number of dominant orientations' they perceived, and the 'strength' with which they perceived each orientation. Test data consisted of 111 grey-level images of natural textures taken from the Brodatz album, a standard collection used in computer vision and image processing. Results show that the computer and humans chose at least one of the same dominant orientations on 95 of the natural textures. Of these textures, 74 were also in 100% agreement on the location of all the dominant orientations chosen by both humans and computer. Disagreements are analyzed and possible causes are discussed. Some apparent limitations in the current filter shapes and sizes are illustrated, as well as some (surprisingly small) effects believed to be caused by semantic recognition and gestalt grouping. PMID- 7993879 TI - Segmenting textured 3D surfaces using the space/frequency representation. AB - Segmenting 3D textured surfaces is critical for general image understanding. Unfortunately, current efforts of automatically understanding image texture are based on assumptions that make this goal impossible. Texture-segmentation research usually assumes that the textures are flat and viewed from the front, while shape-from-texture work assumes that the textures have already been segmented. This deadlock means that none of these algorithms will work reliably on images of 3D textured surfaces. An algorithm has been developed by the authors that can segment an image containing nonfrontally viewed, planar, periodic textures. The spectrogram (local power spectrum) is used to compute local surface normals from small regions of the image. This algorithm does not require unreliable image feature detection. Based on these surface normals, a 'frontalized' version of the local power spectrum is computed that shows what the region's power spectrum would look like if viewed from the front. If neighboring regions have similar frontalized power spectra, they are merged. The merge criterion is based on a description length formula. The segmentation is demonstrated on images with real textures. To the authors' knowledge, this is the first program that can segment 3D textured surfaces by explicitly accounting for 3D shape effects. PMID- 7993878 TI - The effect of similarity and duration on spatial interaction in peripheral vision. AB - Spatial interactions are extensive in the peripheral visual field, extending up to about half the retinal eccentricity of the target (Toet and Levi, Vision Res. 32, 1349-1357, 1992). In the present study it is shown that the degree and extent of peripheral spatial interaction depends in large measure on the similarity between test and flanking stimuli. The stimulus consisted of a test T surrounded by four distracting flanking Ts, each randomly oriented. The task was to determine the orientation of the test T. The test and flanking Ts differed in contrast polarity, shape, depth, color, eye of origin, or contrast. When the target and flanks differed in contrast polarity, depth, or shape, performance improved markedly for all observers. A color difference enhanced the performance of most but not all observers. Eye-of-origin had no effect, that is, spatial interaction was identical when the target and flanks were presented to the same eye, or to opposite eyes. The role of stimulus duration in spatial interaction was examined in two additional experiments. In the first, the stimulus viewing duration was increased in order to allow the observer time to serially search for the test T. In the second experiment, a postmask was presented at the location of the test T. The results of these experiments showed that the influence of similarity was independent of stimulus duration and the postmask, and suggest that serial search does not play an important role in the spatial interaction effects reported here. The extent of spatial interaction is correlated with the ability to do parallel search. PMID- 7993881 TI - Regulation of phospholipid degradation and biosynthesis in the heart by isoprenaline: effect of mepacrine. AB - We investigated the effect of isoprenaline (IPRO), a beta-mimetic catecholamine, on incorporation (32P)Pi into phospholipids of the mouse left ventricle in vivo. All experimental groups of male mice received an injection of (32P)Pi (250 MBq x kg-1 b.w.) intraperitoneally two hours prior to sacrifice. A single dose of IPRO (5 mg x kg-1 b.w.) was injected one hour before killing. IPRO increased the specific radioactivity of phosphatidylcholine (PC) by a factor of 1.8, diphosphatidylglycerol (DPG) 2.1, sphingomyelin (SM) 3.5, phosphatidylinositol (PI) 1.7, phosphatidylserine (PS) 1.7, phosphatidylglycerol (PG) 1.7, phosphatidic acid (PA) 2.0 compared to control values. On the other hand, IPRO is also known to stimulate phospholipid degradation by activation of phospholipase A2. That is why we used mepacrine (50 mg x kg-1 b.w.), a phospholipase inhibitor, to find a possible link between biosynthesis and degradation of phospholipids. Pretreatment with mepacrine two hours prior to sacrifice suppressed IPRO stimulated incorporation of (32P)Pi into phospholipids nearly to control levels. Mepacrine itself did not significantly influence the specific radioactivity of phospholipids. We conclude that phospholipase A2 inhibitor, mepacrine, is able to prevent IPRO-stimulated incorporation into phospholipids, suggesting a feedback relation between their biosynthesis and degradation in the myocardium. PMID- 7993880 TI - Blood pressure regulation in ANF-transgenic mice: role of angiotensin and vasopressin. AB - Transgenic mice overexpressing a transthyretin promoter-ANF structural fusion gene have a life-long reduction in arterial blood pressure compared to nontransgenic littermates. The present study was designed to test the hypothesis that the high plasma level of ANF in the transgenic mice inhibits the renin angiotensin and/or vasopressin systems, thereby causing the hypotension. Mice were anaesthetized with Inactin and arterial pressure and heart rate were monitored before and during Saralasin infusion and vasopressin V1 receptor blockade. Effectiveness of the blockade was determined by injection of angiotensin and vasopressin before and during Saralasin and V1 receptor antagonist administration. Saralasin was associated with hypotension in both transgenic and nontransgenic mice. The decrease in blood pressure was proportionally greater in the transgenic animals. Vasopressin receptor blockade had little effect on blood pressure in either group. Heart rates were not different between the groups during any maneuver. We conclude that the chronic hypotensive effect of ANF overproduction does not involve the inhibition of either renin-angiotensin or vasopressin systems. The data, however, suggest that the renin-angiotensin system may be stimulated in the ANF-transgenic mice. PMID- 7993882 TI - In vitro separation of embryonic chick skeletal muscle myoblasts and fibroblasts: comparison of their characteristics. AB - The aim of the present experiments was to test two methods of separating myoblasts and fibroblasts (selective plating, differential trypsinization) from chick embryonal skeletal muscle and to compare their characteristics. Ornithine decarboxylase (ODC) activity, the amount of incorporated [3H]leucine into proteins and incorporation of [3H]thymidine into DNA were significantly higher in myoblasts than in fibroblasts separated by selective plating. When comparing myoblasts and fibroblasts separated by differential trypsinization, significantly higher ODC activity and greater incorporation of [3H]leucine into protein, but no incorporation of [3H]thymidine into DNA, were found in myoblasts. Higher ODC activity and greater incorporation of labelled leucine were found in fibroblasts separated by the selective plating than in fibroblasts separated by differential trypsinization. The incorporation of labelled thymidine into DNA was higher in myoblasts separated by selective plating than in myoblasts obtained by differential trypsinization. The method of selective plating appears to be simpler and adequate for obtaining myoblastic and fibroblastic cell cultures with sufficiently low mutual contamination. The method of differential trypsinization involves a more drastic treatment of cells and is more time consuming. PMID- 7993883 TI - An unusual temperature dependence of malondialdehyde formation in Fe2+/H2O2 initiated lipid peroxidation of phosphatidylcholine liposomes. AB - Determination of malondialdehyde is a widely used procedure for measurement of lipid peroxidation. In this paper we report an unusual temperature dependence of malondialdehyde formation in egg yolk phosphatidylcholine liposomes oxidized by the Fenton system (0.1 mmol/l FeSO4 and 0.05 mmol/l H2O2). The amount of malondialdehyde formed was 37% higher in samples kept at 22 degrees C than at 50 degrees C. An alternative method for determination of lipid peroxidation, measurement of oxygen uptake, revealed complete consumption of dissolved oxygen to peroxidized lipids at 22 degrees C as well as 50 degrees C. Since oxygen is essential for the formation of cyclic peroxides--precursors of malondialdehyde- we conclude that the nature of the observed effect consists in limitation of oxygen availability at elevated temperatures. PMID- 7993884 TI - The lipid peroxidation in various parts of the rat brain: effect of age, hypoxia and hyperoxia. AB - The effect of normobaric oxygen atmosphere on hypoxia-enhanced lipid peroxidation in the brain cortex, subcortical structures, medulla oblongata and in the cerebellum was observed in 7- and 21-day-old and adult rats. The production of free oxygen radicals causing lipid peroxidation was assessed by the method described by Ohkawa et al. (1979). The rats were exposed for 30 min to 100% oxygen atmosphere which significantly stimulated the production of malondialdehyde (MDA) in all the studied regions of the brain in 7- and 21-day old male rats, and in the brain cortex and subcortical structures of adult males. Higher levels of MDA were found in the brain cortex of 7-day-old female rats only. Reoxygenation with pure oxygen after 30 min hypobaric hypoxia corresponding to 9000 m increased MDA production in all studied parts of the brain on both male and female rats 7- and 21-day-old. In adult rats significantly increased MDA production was only found in the brain cortex of male and female rats and in the subcortical structures of males. The exposition to hypobaric hypoxia followed by reoxygenation by atmospheric air enhanced MDA production in all studied regions of the brain in 7-day-old males and in the cerebellum of females; in 21-day-old rats of both sexes a significant increase of MDA was detected in all parts of the brain. In adult rats were found higher MDA levels in the cerebral cortex of both males and females. PMID- 7993885 TI - Levels of energy-related metabolites in intact and isolated perfused-superfused rat skeletal muscles. AB - Adenosine 5'-triphosphate (ATP), phosphocreatine (PCr), creatine (Cr), inorganic phosphate (Pi), lactate (LAC), pyruvate (PYR) and glycogen as glucose (GLU) were determined and free adenosine 5'-diphosphate (ADP) was calculated from ATP:creatine phosphokinase (CPK) reaction in the gracilis muscle of cold acclimated rats in vivo, and in completely isolated muscles under medium perfusion and superfusion in vitro, using the freeze-clamping method. The mean in vivo levels (mumol/g w.w.) were: ATP 4.8, PCr 12.0, Cr 7.8, Pi 16.1, LAC 1.6, PYR 0.09, GLU 22.9, ADP 0.62 x 10(-3). Isolation of the muscle (about 11 min of anoxia followed by perfusion in the air with a high pO2 medium) decreased macroergic phosphate levels (ATP 3.0, PCr 8.3). In isolated muscles perfused with a high pO2 medium (99 kPa O2, perfusion rate 70 microliters/min) and simultaneously superfused with a low pO2 medium (6.2 kPa O2, 2.3 ml/min) at 28 degrees C in vitro the levels of metabolites were (mumol/g w.w.): ATP 3.1, PCr 8.5, Cr 5.6, Pi 9.2, LAC 2.1, PYR 0.19, GLU 6.6, ADP 0.44 x 10(-3). The mean steady oxygen uptake of the isolated muscle was 97 nmol O2 x min-1 x g-1 w.w. Thus, the levels of macroergic phosphates and their derivatives are lower after isolation and perfusion of the muscle, but the creatine charge [PCr]/([PCr]+[Cr]) remains stable (0.61 in vivo versus 0.60 in the isolated muscle). This indicates that the steady-state and high energy status of the isolated perfused-superfused gracilis muscle is maintained [corrected]. PMID- 7993886 TI - Gastric antiulcer activity of pentacaine: possible mechanism of action. AB - The effect of pentacaine on different models of gastric and duodenal damage and on gastric acid secretion was studied after oral and parenteral administration. A proportional involvement of local and systemic effects of pentacaine was found in phenylbutazone-induced and cold-resistant stress-induced lesions, whereas in ethanol-induced lesions oral administration was the only effective way. On the other hand, duodenal lesions and gastric acid secretion were substantially affected by parenteral administration. The possible mechanisms involved in these differences are discussed. PMID- 7993887 TI - Binaural monopolar galvanic vestibular stimulation reduces body sway during human stance. AB - The influence of monopolar binaural galvanic stimulation of the vestibular system was studied on body sway. Subjects, with eyes closed, were standing on a hard support or on foam rubber. Their body sway was registered on a force platform at intervals of 50 s. Both polarities of direct current with intensity 1 mA were used as a galvanic stimulus during the whole recording interval. Changes of body sway amplitude and velocity were analyzed in situations with and without galvanic stimulation on two different support surfaces. In stance on the hard support, the cathodal polarization of labyrinths (in most subjects) reduced body sway velocity and decreased body sway slightly in the anteroposterior direction. Anodal polarization of labyrinths during 50 s did not affect the body sway parameters. The results on the foam rubber platform exhibited a significant reduction of body sway velocity induced by both anodal and cathodal polarization of the labyrinths. The decrease of body sway in the anteroposterior direction was also observed during cathodal polarization. The stabilizing effect of vestibular binaural monopolar stimulation on the upright stance was mainly observed in the postural control situation where the leg proprioceptive input was changed (stance on soft surface) and the role of vestibular input was more important. PMID- 7993888 TI - Universal multifunctional IBM PC I/O board for clinical examinations and experimental research in neuroscience. AB - The PC is and will remain a basic instrument in the laboratory arsenal in the next few years. The key role of the IBM PC and its clones prompted us to develop a universal multifunctional I/O board (UNIMUL) for this computer. The board will make it possible to use the IBM PC for a wide range of tasks from a simple interface for laboratory processing of data to complex IBM PC-based instruments, e.g. a stimulator, signal analyzer, chart recorder. The present article summarizes the experience gathered during the design and application of the described I/O board in more than 10 different IBM PC-based laboratory and clinical systems listed in the Appendix. An example of the application of the I/O board is presented in the conclusion of this report together with the discussion of the future role of new Application-Specific Integration Circuits (ASICs) and single chip processors in this domain. PMID- 7993889 TI - Cold-activated growth of rat brown adipose tissue in the neonatal period. AB - Repeated exposure of newborn rats to a short-term cold load between day 10 and 30 after birth stimulates the physiological growth rate of the brown adipose tissue. This indicates that in the neonatal period the brown adipose tissue has no reserve thermogenic capacity to compensate an additional cold load and therefore the rate of tissue growth must be activated. PMID- 7993891 TI - Recombinant inbred strains in hypertension research. PMID- 7993890 TI - The mushroom Pleurotus ostreatus accelerates plasma very-low-density lipoprotein clearance in hypercholesterolemic rat. AB - The administration of a diet containing 5% of dried oyster mushroom to male Wistar rats fed a cholesterol diet (0.3%) shortly after weaning for 8 weeks reduced cholesterol levels in the serum and liver by 27 and 33%, respectively and increased the fractional turnover rate of 125I-very-low-density lipoproteins (VLDL) by more than 30%. PMID- 7993892 TI - Phosphorylation of the alpha- and beta-isoforms of DNA topoisomerase II is qualitatively different in interphase and mitosis in Chinese hamster ovary cells. AB - Qualitative differences between interphase and mitotic topoisomerase II were studied in Chinese hamster ovary cells. Differences in sites of phosphorylation of in vivo 32P-labeled topoisomerase II alpha were observed between mitosis and interphase by one-dimensional phosphopeptide mapping of partial tryptic digests. Two-dimensional phosphopeptide mapping of complete trypsin digests revealed two phosphopeptides unique to interphase and three phosphopeptides unique to mitosis. A reduced electrophoretic mobility on denaturing gels (approximately 190 kDa) was observed for the beta-isoform of topoisomerase II in mitosis relative to interphase. Treatment of lysates with alkaline phosphatase demonstrated that this was due to phosphorylation of mitotic topoisomerase II beta. The existence of interphase- and mitosis-specific sites of phosphorylation of topoisomerase II alpha, along with the electrophoretic mobility shift caused by phosphorylation of topoisomerase II beta in mitosis, demonstrates qualitative differences between interphase and mitosis in the phosphorylation state of both isoforms of topoisomerase II. PMID- 7993893 TI - Cyclic GMP formation in rat cerebellar slices is stimulated by endothelins via nitric oxide formation and by sarafotoxins via formation of carbon monoxide. AB - Involvement of a cyclic GMP pathway in signal transduction stimulated by endothelins (ETs) and sarafotoxins (SRTXs) was explored using rat cerebellar slices. These peptides activated the same receptor binding sites (ET-1 and SRTX-b at the picomolar sites; ET-3 and SRTX-c at the nanomolar sites) to produce cyclic GMP, but their signaling pathways differed. The endothelins (ET-1 and ET-3) were found to signal via nitric oxide formation and to involve pertussis toxin sensitive G-protein(s). The SRTXs (b and c), while also stimulating cyclic GMP production, did so via a pathway which is not L-arginine-dependent, i.e., carbon monoxide formation, and did not involve pertussis-toxin-sensitive G-protein(s). This is the first demonstration that the signaling pathways of endothelins and sarafotoxins may differ, even though they share the same binding sites. PMID- 7993894 TI - Dynamic surface properties of pulmonary surfactant proteins SP-B and SP-C and their mixtures with dipalmitoylphosphatidylcholine. AB - Dynamic cyclic surface pressure (pi)-area measurements were performed on surfactant proteins SP-B and SP-C in pure and binary spread films with dipalmitoylphosphatidylcholine (DPPC). When the films of pure SP-B and SP-C were compressed beyond their collapse points (about 40 mN m-1), no appreciable irreversible loss of material occurred and the successive compression isotherms were reproducible. A similar reversible collapse for the proteins was observed when their binary films with DPPC were compressed up to high surface pressures (pi approximately 65 mN m-1), which did not surpass the collapse for DPPC (about 72 mN m-1). In this case, SP-B, squeezed out at 50 mN m-1 during compression of the SP-B/DPPC monolayers that contained > or = 10 weight % protein, reinserted in the films during their subsequent expansion. Likewise, SP-C-DPPC complexes were reversibly excluded at pi approximately 55 mN m-1 from the SP-C/DPPC films that contained > or = 5 weight % protein. Dynamic compression of the mixed protein lipid films beyond the collapse pressure of DPPC showed that SP-B and SP-C improved the respreading of DPPC in a concentration dependent manner. SP-B was more effective in promoting the respreading of DPPC than was SP-C, as indicated by the collapse plateau length ratio criterion. The results from this study suggest a possible interfacial role for SP-B and SP-C in lipid replenishment at the alveolar-air interface, through enhancement of the respreading of DPPC collapse phases (SP-B and SP-C) or through reversible removal of phospholipid (SP C) during dynamic cyclic compression-expansion of the alveolar surface. PMID- 7993895 TI - Identification of amino acids in the N-terminal SH2 domain of phospholipase C gamma 1 important in the interaction with epidermal growth factor receptor. AB - Photoaffinity labeling and site-directed mutagenesis have been used to identify amino acid residues of the phospholipase C gamma 1 (PLC gamma 1) N-terminal SH2 domain involved in recognition of the activated epidermal growth factor receptor (EGFR). The photoactive amino acid p-benzoylphenylalanine (Bpa) was incorporated into phosphotyrosine-containing peptides derived from EGFR autophosphorylation sites Tyr992 and Tyr1068. Irradiation of these labels in the presence of SH2 domains showed cross-linking which was time-dependent and specific; labeling was inhibited with non-Bpa-containing peptides from EGFR in molar excess. The phosphotyrosine residue on the peptides was important for SH2 recognition, as dephosphorylated peptides did not cross-link. Radiolabeled peptides were used to identify sites of cross-linking to the N-terminal SH2 of PLC gamma 1. Bpa peptide SH2 complexes were digested with trypsin, and radioactive fragments were purified by HPLC and analyzed by Edman sequencing. These experiments showed Arg562 and an additional site in the alpha A-beta B region of the SH2 domain, most likely Glu587, to be labeled by the Tyr992-derived peptide. Similar analysis of the reaction with the Tyr1068-derived photoaffinity label identified Leu653 as the cross-linked site. Mutation of the neighboring residues of Glu587 decreased photo cross-linking, emphasizing the importance of this region of the molecule for recognition. These results are consistent with evidence from the v-Src crystal structure and implicate the loop spanning residues Gln640-Ser654 of PLC gamma 1 in specific recognition of phosphopeptides. PMID- 7993896 TI - Self-association and DNA binding of lambda cI repressor N-terminal domains reveal linkage between sequence-specific binding and the C-terminal cooperativity domain. AB - The effects of temperature, protons, and KCl on self-assembly and site-specific binding of lambda cI N-terminal domains with operator sites OR were studied to assess the roles of these domains in DNA binding and cooperativity of the natural system. Domain self-assembly was studied using sedimentation equilibrium while domain-OR interactions were analyzed by quantitative DNase footprint titration. The self-assembly reactions were modeled best as a monomer-dimer-tetramer stoichiometry. Compared with intact cI, the monomer-dimer assembly is energetically weak and is largely independent of pH and KCl. The van't Hoff enthalpy of dimerization was found to be large and positive (+ 10.8 kcal/mol), in sharp contrast to that of intact cI (i.e., -16.1 kcal/mol; Koblan & Ackers, 1991a), indicating that different driving forces dominate the respective assembly processes. The interactions of OR with N-terminal domains were noncooperative under all conditions studied. Binding at each site is accompanied by a negative enthalpy (large at site 1, small at sites 2 and 3). Identical values for salt release and proton absorption were found for the three sites. Comparisons with the analogous thermodynamic parameters from our previous studies indicate that N terminal domains exhibit different linkages to pH, KCl, and T from those of intact cI-OR interactions. This implies that the domains do not act independently within the intact repressor. Since the linkage differences are dependent upon which site the proteins are binding, the C-terminal domain must play a role in repressor discrimination between specific sites. PMID- 7993897 TI - Stimulation of transcription in cultured cells by high mobility group protein 1: essential role of the acidic carboxyl-terminal region. AB - Several in vitro studies have suggested that high mobility group (HMG) protein 1 has a role in gene regulation as a trans activator or quasi-transcription factor. However, data on the molecular functions of HMG1 protein in these reactions are contradictory or obscure. In order to assess whether HMG1 protein does, in fact, have transcriptional activation potential, two assay systems in cultured cells were employed. HMG1 protein introduced into COS-1 cells as a complex with a reporter plasmid carrying the lacZ gene enhanced the level of the gene expression. Cotransfection of an expression plasmid carrying HMG1 cDNA into the cells with the reporter plasmid enhanced the activity of beta-galactosidase 2-3 fold in comparison with that of the control effector plasmid. The enhancement was proved to be dependent not on the replication but on the transcription of the reporter plasmid. In the cotransfection experiments, an expression plasmid the HMG1 molecule lacking the acidic carboxyl terminus repressed the expression of the reporter gene. The binding of an HMG1 protein variant lacking the acidic carboxyl terminus to DNA gave an extremely large shift of gel retardation in comparison with the complete HMG1 molecule. Together, these results indicate that HMG1 protein can enhance expression in cells in culture at the step of gene transcription and that the DNA binding domains comprising two-thirds of the HMG1 protein molecule are responsible for the inhibition property. Also, the acidic terminus of the HMG1 molecule is essential for the enhancement of gene expression in addition to elimination of the repression caused by the DNA binding. (ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7993898 TI - Major cell surface-located protein substrates of an ecto-protein kinase are homologs of known nuclear proteins. AB - Cell surface polypeptides serve as substrates for a casein kinase-like ecto protein kinase activity which is demonstrable under stringent criteria with intact cells using micromolar levels of extracellular [gamma-32P]ATP. Two major 32P-labeled proteins, designated as pp100 and pp120 after their apparent molecular masses on SDS-PAGE under reducing and nonreducing conditions, have repeatedly appeared in the phosphoprotein spectra of different cell types. We have chosen HeLa cells as a source for the biochemical characterization and isolation of pp100 and pp120. Phosphorylation of pp100 and pp120 occurs in their extracellular domains at seryl residues of amino acid side chains. Several criteria deduced from the heparin sensitivity of the ecto-protein kinase and its substrate-induced shedding into the cell supernatant indicated that surface phosphorylation is a function of the ecto-protein kinase. The radioactive phosphorylation of pp100 and pp120 which coincides with their biotinylation on 2D blots can be reversed by mild trypsination of intact cells. Purification and enrichment of pp100 and pp120 were achieved on the basis of radioactivity detection on and isolation from 1D- and 2D-gels. Amino acid sequence analysis performed on tryptic digests of purified ecto-phosphoproteins in most cases showed significant consensus sequences between pp100 and the nuclear RNA-binding protein nucleolin while pp120 sequences proved to be related to hnRNP U, a nucleoplasmic pre-mRNA-binding protein. Immunochemical analysis using anti nucleolin and anti-hnRNP U antibodies combined with comparative phosphorylation and characterization of the ecto-proteins with authentic nucleolin and hnRNP U further established the close relationship, suggesting surface membrane versions of the nuclear proteins. PMID- 7993899 TI - Subcellular localization of specific inositol 1,3,4,5-tetrakis([3H]phosphate) binding sites in rat liver membrane fractions: a comparative evaluation of pH sensitivity and binding characteristics. AB - Inositol 1,3,4,5-tetrakis([3H]phosphate) ([3H]IP4) binding sites were investigated in plasma membranes, nuclei and microsomes derived from the rat liver. The pH optimum for maximum [3H]IP4 binding was not the same for plasma membranes, pH 7.5, nuclei, pH 6.5, and microsomes, pH 8.0. Evidence is presented demonstrating that inositol 1,3,4,5-tetrakis(phosphate) (IP4) was the most effective inositol phosphate in displacing the binding of the [3H]IP4 in all the membrane fractions studied. Furthermore, the rank order of inhibition in various membrane fractions was identical; i.e., IP5, Ins(3,4,5,6), and IP3. This suggests that similar types of putative IP4 receptor proteins are dealt with in the plasma membranes, nuclei, and microsomes. Scatchard analysis of saturation isotherms revealed a single binding site in the plasma membranes and in the microsomes, whereas two binding sites marked by distinct KD and Bmax values were found in the nuclei. The density of putative IP4 binding sites in the plasma membranes corresponded to that of the high-affinity ones in the nuclei. Microsomes contained fewer binding sites as compared with plasma membranes or nuclei. On the basis of the pH sensitivity of [3H]IP4 binding and the KD and Bmax values in various membrane compartments, it is proposed that inositol 1,3,4,5 tetrakis(phosphate) receptor proteins are similar but not identical in membrane fractions in rat liver. Plasma membrane [3H]IP4 binding was displaced with IP4 and IP6, revealing IC50 values of 8 +/- 2 and 150 +/- 20 nM, respectively, indicating that rat liver plasma membrane IP4 receptor is not clathrin assembly protein AP-2.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7993900 TI - Phospholipase A2 engineering. Structural and functional roles of the highly conserved active site residue aspartate-49. AB - Site-directed mutagenesis and high-resolution two-dimensional (2D) proton nuclear magnetic resonance (NMR) were used to probe the structural and functional roles of a highly conserved residue, Asp-49, in the interfacial catalysis by bovine pancreatic phospholipase A2 (PLA2, overexpressed in Escherichia coli). According to crystal structures, the side chain carboxylate of Asp-49, along with the carbonyl oxygens of Tyr-28, Gly-30, and Gly-32, and two water molecules, provides the necessary ligands for Ca2+ which is essential for the enzymatic activity. The Asp-49 of PLA2 was changed to Asn, Glu, Gln, Lys, and Ala; the resulting mutants are named D49N, D49E, D49Q, D49K, and D49A, respectively. The conformational stabilities of all five mutants are similar to that of WT as judged by guanidine hydrochloride-induced denaturation. The structural analyses by NMR indicated no global perturbations upon substitutions, although localized conformational perturbations can be observed for less conserved replacements. Direct Ca2+ binding studies showed no specific binding for D49A, D49N, D49Q, and D49K; however, D49E retains a 12-fold weaker calcium binding affinity (Kd,Ca = 23 mM). The specific activities of all five mutant enzymes decrease significantly, ranging from 5.4 x 10(2)- to 5.8 x 10(5)-fold in comparison with that of the wild type enzyme. The observed activities of mutants require the presence of Ca2+. This demonstrates the functional importance of Asp-49 in the catalytic mechanism of PLA2, presumably by helping to bind and properly orient Ca2+.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7993901 TI - Enoyl-coenzyme A hydratase-catalyzed exchange of the alpha-protons of coenzyme A thiol esters: a model for an enolized intermediate in the enzyme-catalyzed elimination? AB - 3-Quinuclidinone catalyzes the exchange of the alpha-protons of butyryl-coenzyme A (CoA) with a second-order rate constant of 2.4 x 10(-6) M-1 s-1. In contrast, enoyl-CoA hydratase catalyzes the stereospecific exchange of the pro-2S proton of butyryl-CoA with a maximum second-order rate constant of ca. 8 x 10(2) M-1 s-1. This isotope exchange reaction is completely stereospecific within the limits of experimental detection (over 600-fold). The enzyme-catalyzed exchange is dependent on pD, decreasing above a pKa of 8.8 and below a pKa of 8.1, but independent of the buffer concentration. The stereospecificity of the exchange was unexpected because the pro-2R hydrogen is abstracted during the enzyme catalyzed dehydration of 3(S)-hydroxybutyryl-CoA. In spite of the ability to exchange the pro-2S hydrogen, the stereospecificity of the dehydration reaction was determined to be better than 1 in 10(5) as no incorporation of 2H into the alpha-position of crotonyl-CoA or into the pro-2S position of 3(S)-hydroxybutyryl CoA was detected during prolonged equilibrations with enoyl-CoA hydratase. Both the exchange of the alpha-proton and the dehydration activity of the enzyme are diminished by over 100-fold in a site-directed mutation of rat liver enoyl-CoA hydratase, where glutamate-164 is changed to glutamine, strongly suggesting that the same active site base is responsible for proton abstraction in both the dehydration and solvent exchange reactions. The enoyl-CoA hydratase-catalyzed exchange of the alpha-protons becomes nonstereospecific when the acidity of the alpha-protons is enhanced. While alpha-proton abstraction can be observed when no elimination reaction is possible, there is no evidence for proton abstraction without elimination in the crotonase equilibrations with 3(S)-hydroxybutyryl-CoA, 3-hydroxypropionyl-CoA, or 3-chloropropionyl-CoA. The differences in the isotope exchange and dehydration reactions emphasize the importance of the 3-hydroxyl group in promoting elimination and are consistent with a concerted elimination mechanism. PMID- 7993902 TI - Stereochemistry and kinetics of the hydration of 2-acetamido-D-glucal by beta-N acetylhexosaminidases. AB - Hydrolysis by three beta-N-acetylhexosaminidases (human placenta, jack bean, and bovine kidney) is shown to occur with the retention of anomeric configuration, most likely via a double-displacement mechanism involving the formation and hydrolysis of a glycosyl-enzyme intermediate. 2-Acetamido-D-glucal is shown to be a slow, tight-binding substrate for the jack bean enzyme, with Vmax and Km values of 0.48 +/- 0.01 unit/mg and 27 +/- 2.8 microM, respectively. The same substrate is also bound very tightly by the human and bovine enzymes, with Ki values of 8 and 25 microM, respectively. All three enzymes hydrate 2-acetamido-D-glucal, yielding N-acetyl-D-glucosamine as the product in each case. This is the first time that proton transfer has been shown to occur from the top face during the hydration of a glycal by a retaining beta-glycosidase. Kinetic studies of this hydration reaction with the jack bean enzyme demonstrate that the tight binding observed is due to the formation of a high-affinity, reversible complex, and not due to the accumulation of a reaction intermediate. This indicates that correctly substituted glycals might act as transition state mimics and suggests approaches to the design of high-affinity inhibitors of beta-N-acetylhexosaminidases. PMID- 7993903 TI - Substituent effects in the carboxypeptidase A catalyzed hydrolysis of substituted L,beta-phenyllactate esters. AB - The carboxypeptidase A catalyzed hydrolysis of an extensive series of substituted cinnamoyl-L,beta-phenyllactate esters has been investigated. Plots of kcat vs pH are sigmoidal in the pH range 5-9 with an average apparent pKaES of 6.6 +/- 0.1. The values of Km are pH independent in the range pH 5-8. Plots of log kcat/Km vs pH give pKaE values of 6.4 and 9.0 that do not vary significantly through the series. A plot of log kcat (pH 8) vs sigma, the Hammett substituent constant, is linear with a slope rho of 0.5, while log Km vs sigma has a slope of -0.4. The plot of log kcat/Km vs sigma is also linear with rho = 0.9. The Hammett plots are linear at both pH 6 and 8 with closely similar slopes, which indicates that the apparent pKaES near pH 6 does not reflect a change in the rate-determining step. The enzymatic reactions and the nonenzymatic OH- catalyzed hydrolysis reactions are affected alike by changes in the substituent groups; a plot of log kOH, the second-order rate constant for alkaline hydrolysis of the esters, vs log kcat/Km is linear with a slope of 0.9. There is little effect of changing the substituent group in the nonenzymatic pH-independent hydrolysis of the Zn(II) complex of corresponding 4-substituted cinnamic acid 6-carboxypicolinic acid anhydrides (rho < or = 0.1).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7993904 TI - On the heterogeneity of the M population in the photocycle of bacteriorhodopsin. AB - The M stage in the photocycle of bacteriorhodopsin (bR), a key step in its light induced proton pump mechanism, is studied in water/glycerol suspensions over the temperature range between 20 and -60 degrees C. The biexponential decay of M is analyzed for wild-type (WT) bR and for its D96N, Y185F, and D115N mutants, at various pH values, according to the scheme: bR-->(hv) L-->M<-->(k1, k-1) N-->(k2) bR. The analysis leads to the conclusion that the N state is generated, with analogous rate parameters, in all cases, including the D96N mutant. Another approach involves probing the M state, generated by steady-state illumination at 60 degrees C, by fast cooling to -180 degrees C. Subsequent irradiation with blue light, followed by gradual warming up, induces the M-->(hv) M'-->bR'-->bR sequence of reactions. On the basis of characteristic difference spectra and transition temperatures observed for the M'-->bR' process, it is concluded that the initially observed M state at -60 degrees C, denoted as (M)a, is composed of three (or four) equilibrated substrates, MI, MII, MIII, and MIV. During the M-->N equilibration, which corresponds to the fast phase of the M decay, (M)a transforms into a second state, (M)b, in which MIII has been replaced by a fifth M substate, denoted as MV. MV is identified as the protein state in which an appropriate structural change allows reprotonation of the Schiff base, generating the N state. The low-temperature heterogeneity in M is discussed in terms of the two M states (M1 and M2) previously postulated [Varo, G., & Lanyi, J. K. (1990) Biochemistry 29, 2241] for the room temperature photocycle. The following conclusions are derived for both low and room temperature photocycles: (a) The M population is highly heterogeneous and pH dependent. (b) At least three transitions are observed between the initially formed M state and the M state that is equilibrated with N. These are assigned to protein conformational changes and to water molecule rearrangements. (c) In an aqueous suspension of WT bR at room temperature, the Schiff base reprotonation is controlled by D96. However, our results show that the formation and stability of the N state do not require the D96 residue. Moreover, at low temperatures, the (M)a-->(M)b protein structural transformation, which has not yet been resolved at room temperature, becomes the rate-determining step in the protonation of the Schiff base. PMID- 7993905 TI - Does slow energy transfer limit the observed time constant for radical pair formation in photosystem II reaction centers? AB - We have used spectrally photoselective femtosecond transient absorption spectroscopy on photosystem II reaction centers to show that there are at least two pools of chlorin molecules/states which can transfer excitation energy to P680, the primary electron donor in photosystem II. It has previously been shown that one chlorin pool equilibrates with P680 in 100 fs [Durrant et al. (1992) Proc. Natl. Acad. Sci. U.S.A. 89, 11632-11636], and we report here the observation of energy transfer from a second more weakly coupled chlorin pool. The effect of the weakly coupled pool is to increase the apparent time constant for radical pair formation from 21 ps when P680 is selectively excited to 27 ps when the accessory chlorins are excited. We conclude that it is possible to observe both radical pair formation somewhat slowed by an energy transfer step and radical pair formation not limited by this slow energy transfer, depending upon which chromophores are initially excited. These observations provide evidence that when using photoselective excitation of P680, the observed 21 ps time constant for radical pair formation is not limited by a slow energy transfer step. PMID- 7993906 TI - Spectroscopic characterization of three different monomeric forms of the main chlorophyll a/b binding protein from chloroplast membranes. AB - A detailed comparison has been made between dichroic steady-state spectroscopic properties at 77 K of several trimeric and monomeric forms of the major chlorophyll a/b binding protein (LHC-II) from pea. Monomeric forms were obtained by applying high concentrations of nonionic detergents, by a lipase treatment, or by a chymotrypsin/trypsin treatment. The latter treatments removed phosphatidyl glycerol essential for trimer formation. The absorption and dichroism spectra indicate that for trimeric LHC-II the chlorophyll b absorption region is centered around 649 nm and is composed of at least five subbands near 640, 647, 649, 652, and 656 nm. The chlorophyll a absorption region is centered around 670 nm and is composed of at least five bands near 661, 668, 671, 673, and 676 nm. The chlorophyll b band near 647 and 652 nm and the chlorophyll a bands near 668 and 673 nm are absent in the circular dichroism spectrum after monomerization. A configuration in which pigments of the same nature located on different monomers become excitonically coupled in the trimer could explain these results. In monomers obtained in high concentrations of nonionic detergents, no additional bands have disappeared, but the absorption spectra of the other two types of monomers lack the bands at 640 and 661 nm. These monomers have lost some chlorophyll a and b according to the fluorescence emission spectra, which show contributions from free chlorophyll a and b. The results suggest that phosphatidyl glycerol not only is involved in trimer formation but also has a structural role within the monomers. PMID- 7993907 TI - Human cathepsin B is a metastable enzyme stabilized by specific ionic interactions associated with the active site. AB - The effect of neutral or alkaline pH on cathepsin B activity and structure was investigated. An irreversible loss of activity, accompanied by large structural changes, was observed at pH > or = 7.0. The high activation energy of 183.5 kJ mol-1, calculated for the inactivation process, is in good agreement with structural changes observed by circular dichroism. Both the pH-induced inactivation and the pH-induced unfolding of cathepsin B were found to be first order processes, exponentially increasing with increasing pH of the solution. The good agreement of the rate constants of inactivation and unfolding of the enzyme indicates an important structure-function relationship. Cathepsin B was also found to be destabilized both by increasing ionic strength and organic solvent content. PMID- 7993908 TI - Kinetic mechanism for the interaction of Hirulog with thrombin. AB - Hirulog (D-FPRPGGGGDGDFEEIPEEYL) is a bivalent inhibitor of thrombin consisting of a moiety (D-FPRP) that binds to the active-site cleft and a hirudin-like C terminal region (DGDFEEIPEEYL) that binds to the positively charged surface groove of thrombin known as the anion-binding exosite. The formation of the thrombin-Hirulog complex was studied using steady-state and rapid kinetics at 37 degrees C. The inhibition constant for Hirulog was found to be 1.9 nM. Hirulog was slowly degraded by thrombin with a kcat value of 0.01 s-1. The formation of the complex resulted in an enhancement of 44% in the intrinsic fluorescence of thrombin. The kinetics of the increase in thrombin fluorescence were described by a double-exponential decay. The dependence of the rate constant for the fast phase on the concentration of Hirulog could be described by the Michaelis-Menten equation with Km and kmax values of 0.75 +/- 0.12 microM and 325 +/- 17 s-1. The data were consistent with a mechanism in which the C-terminal region of Hirulog binds to the anion-binding exosite with a dissociation constant of 0.75 microM in the first step, followed by two intramolecular steps with rate constants of about 300 and 30 s-1. A C-terminal fragment of hirudin was found to compete in the first step confirming that this process corresponded to the binding of the hirudin-like C-terminus of Hirulog to the anion-binding exosite.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7993909 TI - Identifying substrate motifs of protein kinases by a random library approach. AB - Protein phosphorylation is an important posttranslational modification process that plays a crucial role in signal transduction. There are many protein kinases involved in cell signaling. However, substrate motifs of many protein kinases in signal transduction are not well-known. Traditional methodologies for identifying these motifs are often difficult and inefficient. In the present study, we developed a novel approach for discovering linear substrate motifs of protein kinases. This method is based on the screening of random synthetic combinatorial peptide libraries on beads where each bead expresses only one peptide entity [Lam et al. (1991) Nature 354, 82-84]. We chose cyclic AMP-dependent protein kinase (cAPK) as a model system in the present study since it is a well-studied enzyme. Random pentapeptide and heptapeptide libraries were screened with the addition of [gamma-32P]ATP and cAPK. 32P-Labeled peptide-beads were then isolated for microsequencing. The identified peptide motif for cAPK was RRXS and is identical to that reported in the literature. Kinetic studies of the best three peptides indicate that they are efficient substrates for cAPK discovered from random synthetic combinatorial peptide libraries. Our results also suggest that this method is potentially useful for identifying substrate motifs of various protein kinases with high sensitivity and specificity. In addition, this method can also be used as a general method for identifying linear substrate motifs for various posttranslational modifications. PMID- 7993910 TI - NMR solution structure of the C-terminal fragment 255-316 of thermolysin: a dimer formed by subunits having the native structure. AB - The solution structure of the C-terminal fragment 255-316 of thermolysin has been determined by two-dimensional proton NMR methods. For this disulfide-free fragment there was a previous proposal according to which it would fold into a stable helical structure forming a dimer at concentrations above 0.06 mM. A complete assignment of the proton NMR resonances of the backbone and amino acid side chains of the fragment was first performed using standard sequential assignment methods. On the basis of 729 distance constraints derived from unambiguously assigned nuclear Overhauser effect (NOE) proton connectivities, the three-dimensional structure of a monomeric unit was then determined by using distance geometry and restrained molecular dynamic methods. The globular structure of fragment 255-316 of thermolysin in solution, composed of three helices, is largely coincident with that of the corresponding region in the crystallographic structure of intact thermolysin [Holmes, M. A., & Matthews, B. W. (1982) J. Mol. Biol. 160, 623-639]. This fact allowed identification as intersubunit of up to 52 NOE cross correlations, which were used to dock the two subunits into a symmetric dimer structure. The obtained dimeric structure served as the starting structure in a final restrained molecular dynamic calculation subjected to a total of 1562 distance constraints. In the resulting dimeric structure, the interface between the two subunits, of a marked hydrophobic character, coincides topologically with the one between the 255-316 fragment and the rest of the protein in the intact enzyme. The present work decisively shows that the thermolysin fragment 255-316 can attain a stable and nativelike structure independently of the rest of the polypeptide chain. Considering that the thermolysin molecule is constituted of two structural domains of equal size (residues 1-157 and 158-316), the results of this study show that autonomously folding units can be substantially smaller than entire domains. PMID- 7993911 TI - Comparison of crystal structures of two homologous proteins: structural origin of altered domain interactions in immunoglobulin light-chain dimers. AB - The sequence and structure of a second human kappa 1 immunoglobulin light-chain variable domain, Wat, has been determined. The R-factor is 15.7% for 1.9-A data. One hundred and ninety-five water molecules were identified; 30 water molecules were located in identical positions in each of the monomers. Some of the water molecules are integral parts of the domains. This light chain is encoded by the same variable domain gene that encoded the previously characterized kappa I variable domain, Rei. Due to limited somatic mutation, the two highly homologous proteins differ in only 20 of the 108 residues. Wat crystallized in space group P6(4) while Rei crystallized in space group P6(1); in both crystals, the asymmetric unit was the noncovalent dimer. Although the basic domain structure is the same for both proteins, the relative positions of the domains within the two dimers differ. This difference is most likely accounted for by the replacement of Tyr36 in Rei by Phe in the Wat protein. Residue Tyr36 is part of the hydrogen bonding network in the interface between the domains in Rei. Losing the hydrogen bonding capability of residue 36 by replacement of Tyr by Phe alters the network of hydrogen bonds between the domains, resulting in a different domain-domain contact. The details of lattice contacts in the two crystals were compared. One type of contact that extends the beta-sheet of the individual domains was conserved, but because it involved different symmetry elements within the crystal, different crystal packing resulted. In the Wat crystal, one of the contacts shows an example of how a symmetrical binding site can "bind" an asymmetrical object. Further, the examination of the Wat crystal also illustrates how the different crystalline environments of the domains of the dimer results in different distributions of temperature factors for the residues within the domains. PMID- 7993912 TI - 1H, 13C, and 15N resonance assignments and secondary structure analysis of the HU protein from Bacillus stearothermophilus using two- and three-dimensional double- and triple-resonance heteronuclear magnetic resonance spectroscopy. AB - Nearly complete 1H, 13C, and 15N resonance assignments have been obtained for the protein HU from Bacillus stearothermophilus (dimer, 19.5 kDa) using double- and triple-resonance 2D and 3D NMR experiments. This has resulted in assignments of 91% of the observable protons, 98% of all 13C, and 92% of all 15N nuclei. NOEs obtained from a 3D time-shared NOESY-(13C,15N)-HSQC spectrum, exchange data of amide protons, and chemical shifts of the 1H alpha, 1HN, 13C beta, 13C alpha, 13CO, and 15N nuclei have been used to identify the secondary structure elements. Three alpha-helices (residues 3-13, 18-37, and 83-90) and three extended strands (residues 40-45, 48-62, and 67-82) have been found in HU. The arrangement of these elements of secondary structure is very similar to the X-ray structure [Tanaka et al. (1984) Nature 310, 376-381; White et al. (1989) Proteins 5, 281 288]. The conformation of the proposed DNA-binding region of HU, i.e., an antiparallel beta-hairpin, was not observed previously in the X-ray structure. In the NMR structure long range NOEs in the beta-arm region (residues 53-76) suggest a distortion between residue Pro-72 and Ala-73 and between Pro-63 and Gln-64 with concomitant distortions in the opposite strand. The NOE data indicate further that the loop region in the DNA-binding arms of HU is arranged as a type I beta turn from Pro-63 to Gly-66. PMID- 7993913 TI - Hydrogen tunneling in the flavoenzyme monoamine oxidase B. AB - Competitive kH/kT and kD/kT kinetic isotope effects on p-methoxybenzylamine oxidation by the 8 alpha-S-cysteinyl flavin adenine dinucleotide (FAD)-dependent enzyme monoamine oxidase B (MAO-B) have been measured as a function of temperature. At pH 7.5, exponents relating observed kH/kT and kD/kT isotope effects indicate the presence of a temperature-dependent change in rate-limiting step. At lower temperature (e.g., 2 degrees C), the presence of multiple rate limiting steps (commitments) is clearly indicated from the size of the exponent and individual isotope effects. Noncompetitive kH/kD isotope effect measurements indicate a trend in observed isotope effects between pH 9.0 and 6.0, with isotope effects increasing at lower pH. Primary and secondary kH/kT and kD/kT isotope effects were therefore measured as a function of temperature at pH 6.1. Exponents relating primary and secondary kH/kT and kD/kT in the 10-43 degrees C range are 3.13 +/- 0.04 and 2.36 +/- 0.13, respectively, and do not systematically change with temperature. These data indicate that commitments, if present, remain constant across this temperature range. The temperature dependence of the observed primary isotope effects gives values for the ratios of Arrhenius prefactors of 0.13 +/- 0.03 (AH/AT) and 0.52 +/- 0.05 (AD/AT). Both values are well below the lower limits predicted in the absence of tunneling contributions to the reaction coordinate, indicating that both deuterium and protium tunneling take place in this reaction. The presence of a temperature independent commitment contribution cannot be rigorously ruled out; however, the effect of such a commitment on the observed AH/AT and AD/AT values is shown to be quite small. PMID- 7993914 TI - Photoaffinity labeling of the ATP binding domain of Rubisco activase and a separate domain involved in the activation of ribulose-1,5-bisphosphate carboxylase/oxygenase. AB - Photoaffinity labeling of Rubisco activase with 2- and 8-N3ATP was used to identify the adenine binding domain for ATP. Rubisco activase hydrolyzed both of these analogs of ATP and used their hydrolysis to support a low rate of Rubisco activation. When irradiated with ultraviolet light, these and other azido substituted adenine nucleotides covalently modified Rubisco activase at two distinct binding sites. Competition binding experiments with ATP and ADP showed that one of the sites was the ATP binding domain. The other site was not a nucleotide binding domain per se but would bind adenine nucleotides if an azido moiety was present on the base. Tryptophan and other indoles prevented azidoadenine nucleotides from labeling this domain but afforded little protection to the ATP binding domain. The ability to selectively protect each of the two binding sites made it possible to localize the adenine binding domain for ATP to the region of Rubisco activase from N68-D74 and the other binding domain to a region near the N-terminus from Q10 to D14. Modification of the region from Q10 to D14 by photoaffinity labeling prevented Rubisco activase from promoting activation of Rubisco without affecting ATP hydrolysis. These data suggest that a specific region of Rubisco activase near the N-terminus may be a site of interaction with Rubisco. Binding of azidoadenine nucleotides in this region appears to be fortuitous and may involve base-stacking with the species-invariant Trp at position 16 and hydrogen bonding of the azido moiety. PMID- 7993915 TI - Subcellular location of enzymes involved in core histone acetylation. AB - Multiple enzyme forms of histone deacetylase and histone acetyltransferase exist in germinating maize embryos. We analyzed the association of the different enzymes to chromatin by ion exchange chromatography of subcellular fractions from different time points of embryo germination. The vast majority of histone deacetylase HD-1A was not bound to chromatin, since it was solubilized during chromatin isolation, regardless of its phosphorylation state and the phase of embryo germination. In contrast, HD-2 was chromatin bound during the entire germination pathway. Histone deacetylase HD-1B was present in a chromatin-bound and a soluble form; the ratio between these two forms changed during germination. Both nuclear histone acetyltransferases, HAT-A1 and HAT-A2, were tightly chromatin-bound and could only be released from chromatin by salt extraction. To test whether histone acetyltransferases or deacetylases are associated with the nuclear matrix, we analyzed nuclear matrix preparations from yeast, Physarum, and maize step by step for both enzyme activities. This analysis confirmed that part of the activity is chromatin bound, but no significant enzyme activity could be found in the final nuclear matrix, regardless of the preparation protocol. This result was further substantiated by detailed analysis of histone deacetylases and acetyltransferases during cellular fractionation and nuclear matrix preparation of chicken erythrocytes. Altogether our results suggest that the participation of these enzymes in different nuclear processes may partly be regulated by a distinct location to intranuclear components. PMID- 7993916 TI - NMR studies and conformational analysis of a DNA four-way junction formed in a linear synthetic oligonucleotide. AB - A linear DNA oligomer (M(r) 14,000, 46 nucleotides) was especially designed, chemically synthesized, and studied by means of 1H NMR spectroscopy. The design of the oligomer was guided by the idea that incorporation of three short palindromic sequences, each interspersed by 5'-CTTG-3' motifs at predetermined positions in the oligomer, would give rise to the formation of three stable minihairpin loops [Ippel, J. H., et al. (1992) J. Biomol. Struct. Dyn. 9, 1-16], which in turn were expected to encourage further folding of the strand into a stable four-way junction containing three "hairpin" arms and an open-ended duplex stem as the fourth arm. Linear DNA four-way junctions constructed according to this concept can be more compact and are therefore expected to be more suitable as model compounds for conformational studies compared to junctions that are built from two or more separate strands. A stable cruciform conformation was substantiated for the 46-mer in aqueous solution in the presence of Mg2+. Complete sequential 1H NMR assignments of the nonexchangeable protons (except H4', H5', and H5") were obtained with the aid of NOESY and HOHAHA experiments. The NMR data gave evidence for the expected existence of minihairpin-loop structures at the three 5'-CTTG-3' motifs in the sequence. The complementary stem domains adopt a regular B-DNA form. Watson-Crick type base pairing is preserved for all residues in the stem domains, including the residues at the center of the junction. A systematic investigation of the interresidual NOEs observed between the protons of the eight central residues revealed the complete stacking pattern of the residues at the branch point. PMID- 7993917 TI - Mutants affecting nucleotide recognition by T7 DNA polymerase. AB - Analysis of two mutations affecting nucleotide selection by the DNA polymerase from bacteriophage T7 is reported here. Two conserved residues (Glu480 and Tyr530) in the polymerase active site of an exonuclease deficient (exo-) T7 DNA polymerase were mutated using site-directed mutagenesis (Glu480-Asp and Tyr530 Phe). The kinetic and equilibrium constants governing DNA binding, nucleotide incorporation, and pyrophosphorolysis were measured with the mutants E480D(exo-) and Y530F(exo-) in single-turnover experiments using rapid chemical quench-flow methods. Both mutants have slightly lower Kd values for DNA binding compared to that of wild-type(exo-). With Y530F(exo-) the ground state nucleotide binding affinity was unchanged from wild-type for dGTP and dCTP, was 2-fold lower for dATP and 8-10-fold lower for dTTP binding. With E480D(exo-), the binding constants were 5-6-fold lower for dATP, dGTP, and dCTP and 40-fold lower for dTTP binding compared to those constants for wild-type(exo-). The significance of a specific destabilization of dTTP binding by these amino acids was examined using a dGTP analog, deoxyinosine triphosphate, which mimics the placement and number of hydrogen bonds of an A:T base pair. The Kd for dCTP opposite inosine was unchanged with wild-type(exo-) (197 microM) but higher with Y530F(exo-) (454 microM) and with E480D(exo-) (1 mM). The Kd for dITP was the same with wild type(exo-) (180 microM) and Y530F(exo-) (229 microM), but significantly higher with E480D(exo-) (3.2 mM). These data support the suggestion that E480 selectively stabilizes dTTP in the wild-type enzyme, perhaps by hydrogen bonding to the unbonded carbonyl. Data on the incorporation of dideoxynucleotide analogs were consistent with the observation of a selective stabilization of dTTP by both residues. Pyrophosphorolysis experiments revealed that neither mutation had a significant effect on the chemistry of polymerization. The fidelity of the mutants were examined in misincorporation assays. Both E480D(exo-) and Y530F(exo ) showed saturation kinetics with the wrong nucleotide, with binding constants of 1-3 mM compared to the estimated binding affinity of 6-8 mM with wild-type(exo-). Accordingly, both mutants showed slightly lower selectivity against misincorporation. Taken together, these results indicate that E480 and Y530 each contribute to ground state nucleotide binding and suggest that the E480 may serve to specifically stabilize the incoming dTTP of A:T base pairs to compensate for the fewer hydrogen bonds compared to G:C base pairs. PMID- 7993918 TI - DNA cleavage by NaeI: protein purification, rate-limiting step, and accuracy. AB - NaeI endonuclease must bind two DNA sites for cleavage to occur. NaeI was purified to apparent homogeneity and used to determine the rate-limiting step for DNA cleavage and to measure NaeI's specificity for its cognate recognition site. Steady-state cleavage by NaeI in the presence of effector DNA (activated) gave values of 0.045 s-1 and 10 nM for kcat and KM for M13 DNA substrate, respectively, but values of 0.4 s-1 and 170 nM, respectively, for an M13 DNA fragment substrate. Single-turnover cleavage of M13 DNA demonstrated that DNA strand scission is not rate-limiting for turnover of NaeI. Transient kinetic analysis of M13 DNA cleavage by NaeI showed an initial burst of substrate cleavage that was proportional to NaeI concentration, implying that product release is rate-limiting for turnover of NaeI. The NaeI effector and substrate binding sites were found to prefer cognate over noncognate sequences by 10(3) fold and at least 40-500-fold, respectively. kcat for noncognate recognition sequence was at least 10(6)-fold lower than that for cognate. The specificity of activated NaeI, as measured by kcat/KM, for noncognate recognition sequence was 10(8)-fold lower than that for cognate, and over 10(11)-fold lower when the decreased affinity for noncognate sequence at the effector binding site was taken into account. This specificity is approximately 10(4)-fold larger than for any other restriction enzyme measured. PMID- 7993919 TI - Transcription bypass or blockage at single-strand breaks on the DNA template strand: effect of different 3' and 5' flanking groups on the T7 RNA polymerase elongation complex. AB - We have studied the effects of single-strand breaks present on the template strand during T7 RNA polymerase transcription elongation. A synthetic DNA template with a T7 promoter was designed to contain a one-nucleotide gap at a defined location on the template strand. This gap, surprisingly, was efficiently bypassed by T7 RNA polymerase during transcription elongation, and the full length transcript (FLT37) generated from the bypass event was shortened by one nucleotide compared to the full-length transcript (FLT38) generated from an intact, unbroken template strand. FLT37 did not contain any nucleotide insertions opposite to the gap, so that the RNA sequence downstream from the gap, although accurately transcribed, contained a single base deletion compared to FLT38. This, to our knowledge, is the first demonstration that the continuity of the DNA template strand is not a necessary requirement for DNA-dependent RNA polymerase transcription elongation. DNA templates with different 3' and 5' termini at the single-strand break site were also investigated in this study. One of these templates, 1/3P-4P, which contained 3'- and 5'-phosphoryl termini at the break site, efficiently blocked T7 RNA polymerase. A single phosphoryl group present on either the 3' or the 5' terminus of the break site did not efficiently block RNA polymerase progression, suggesting that the blockage observed with template 1/3P 4P is due to the repulsion between the two phosphoryl termini in the vicinity of the polymerase active site. PMID- 7993920 TI - Research on aging: what strategies in the European Union? PMID- 7993921 TI - Humoral immunity in aging. AB - The interactions between B and T lymphocytes, leading to the development of humoral responses, are reviewed with references to the changes occurring in aged people. Aging is perceived as a process of impairment of immune functions; it is known that T cells from aged subjects have a reduced ability to produce IL-2. However, other functions seem to be upregulated in elderly subjects; indeed, IL 1, IL-3, IL-4, IL-6 and TNF alpha production are increased both in aged mice and humans. These cytokines are known to control B cell differentiation, through isotype switch and Ig production. A significant increase in IgG subclasses and IgA is observed in sera of aged subjects. This contrasts with the significant decrease in circulating B lymphocytes. The impairment of primary responses to immunization, and other aspects of humoral immunity, including mucosal responses, autoantibody production and correlations with phenotypic markers of T and B cell subsets, are discussed. PMID- 7993922 TI - Comparison of spouse and nonkin controls: the experience of the Consortium to Establish a Registry for Alzheimer's Disease (CERAD). AB - Normal spouses may be an excellent source of control subjects in research on noninstitutionalized Alzheimer's disease (AD) cases. To determine to what extent spouses might differ from nonkin controls, we compared information on 145 spouses of AD patients with 158 nonkin community volunteers enrolled by 23 centers of the Consortium to Establish a Registry for Alzheimer's Disease. Chi square and 1-way ANOVA analyses indicate that neither at entry nor over the next two years did the two groups of controls differ significantly on demographic characteristics, health status, or performance on neuropsychological measures. However, hierarchical logistic regression showed that, after controlling for demographic characteristics and physical status, dropout was nearly twice as high among spouse controls. Dropout was related to nonreturn of the AD case. Thus, as controls, spouses are viable as long as the cases to whom they are married remain in the study. PMID- 7993923 TI - Comorbidity of other chronic age-dependent diseases in dementia. AB - This study compares the prevalence rates of 5 common age-dependent diseases in non-demented and demented subjects. Control and dementia populations were approximately age-matched and their numbers also approximated. Prevalence rates for hypertension, myocardial infarction (MI), stroke, cancer and diabetes were determined. The rates of two or more coexisting diseases in the same patient were also compared. Two populations were studied: one was designated the autopsy series, and the other the hospital series. In the autopsy series, the rate of cardiomegaly/hypertension was 1.3 times higher in the control than in the dementia population, and for MI it was 1.7 times higher in the former than in the latter. The rate for stroke was higher in the control group by only a factor of 1.1, for cancer by only a factor of 1.2, and for diabetes the rates were almost identical in the two populations. The rate differences were statistically significant only with respect to cardiomegaly and MI. When the non-vascular and vascular dementias were compared, the rates in the latter were higher by only a factor of 1.3 for cardiomegaly, stroke, cancer and diabetes; for MIs, the rates were about the same in the two dementia categories. The data for two or more coexisting diseases were almost identical in control and dementia autopsy populations. In the hospital series, the hypertension rate was 1.6 times higher in the control than in the Alzheimer's disease (AD) group; for MI, the control group was higher by a factor of 1.5.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7993924 TI - Changes in endocrine atrial rat cardiocytes during growth and aging: an ultrastructural, morphometric and endocrinological study. AB - The effects of age on atrial natriuretic factor (ANF) metabolism were studied in male Sprague Dawley rats by standard radioimmunological procedures, transmission electron microscopy, and ultrastructural morphometry. Plasma atrial natriuretic peptide (ANP) levels increased during growth (1-month-old rats: 64 +/- 8.7 pg/mL; 2-month-old rats: 105 +/- 8.1 pg/mL) and did not change thereafter. Immunoreactive (ir)-ANP concentration increased significantly in senescent rats, both in the right (12-month-old rats: 254 +/- 33 ng/mg; 24 month-old: 415 +/- 77 ng/mg) and left atrium (226 +/- 30 and 498 +/- 60 respectively). The ultrastructural morphological features of the endocrine cardiocytes of senescent rats were the presence of a few lysosomal structures and atrial specific granules of higher electron-density. Ultrastructural morphometry studies did not reveal any significant increase in the number or in the mean individual volume of atrial specific granules, compared with young adult rats. In conclusion, unlike younger rats, morphometric data in older and senescent rats show that atrial granularity may not necessarily change together with atrial ir-ANP contents; ir-hormone assay findings show that senescent rats have ANP plasma levels within the norm, and a much larger hormone store in atrial tissue. PMID- 7993925 TI - Improved exercise tolerance by cardiac rehabilitation after myocardial infarction in the elderly: results of a preliminary, controlled study. AB - Elderly patients are commonly excluded from cardiac rehabilitation after myocardial infarction (MI). The present controlled, non-randomized trial was undertaken as a preliminary study to compare some effects of cardiac rehabilitation between patients younger and older than 65 years without contraindications to physical exercise. Baseline total work capacity (TWC) was assessed by a maximal ergometric stress testing 4 weeks after MI. Patients were then prospectively enrolled into an 8-week ambulatory rehabilitation program (R group: age < or = 65 N = 16; age > 65 N = 16). Those who refused or who could not participate in the program because of logistic difficulties served as controls (NR-group: age < or = 65 N = 16; age > 65 N = 14). In spite of non-randomized allocation, clinical characteristics did not differ between either treatment groups or age groups. TWC was re-assessed at 8 weeks from baseline evaluation in all patients. The number of completed training sessions in the R-group, and the proportion of sessions which were suspended for physiological or pathological (adverse events during exercise) causes were similar under and over 65 years. TWC increased (p < 0.001) in the R-group, the improvement being similar in the two age cohorts (< or = 65: +55% vs > 65: +65%, NS). A spontaneous enhancement of TWC (+37%, p < 0.001) occurred among younger controls as well. Only older controls did not improve their TWC; moreover, their +16% change was significantly (p < 0.05) less than the +65% increase obtained by the R-group of the same age.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7993926 TI - The assessment of biological age: a report from the Department of Environment Study. AB - Indicators of ageing were measured in 397 male and 130 female London Civil Servants aged from 37 to 58 years of age. Grey hair, skin inelasticity, and arcus senilis were strongly and independently related to chronological age. Also independently related were serum albumin (negatively related in both sexes), baldness, serum creatinine, systolic blood pressure, serum calcium (negatively) and ESR in men, and serum cholesterol in women. Chronological age was regressed on the above variables for men and women separately to provide regression equations. Biological age for an individual was calculated by entering his or her results and calculating the residuals. Biological age in those who stopped smoking tended to be younger than chronological age by an average of 12-13 months in men and 1-4 months in women. Men and women who had never smoked had higher biological than actual ages but not after adjusting for regression dilution bias. Men who currently smoked had higher biological ages of 2-3 months but not women smokers (4-6 months lower). Similarly, men of lower employment grades had an average biological age 13 months older and women 8 months, compared with higher employment grades. These differences between employment grade appeared to be due to ESR, arcus senilis, systolic blood pressure and serum cholesterol. These four measurements may be markers of biological rather than chronological age, and the value of attempting to measure biological age is discussed. PMID- 7993927 TI - Multiple age-associated mitochondrial DNA deletions in skeletal muscle of mice. AB - Multiple mitochondrial DNA (mtDNA) deletions have been associated with aging in humans and monkeys. Since the inbred mouse strain, C57BL/6, has been extensively studied gerontologically, we sought to investigate its utility as a model for examining the importance of mtDNA deletions in aging. Using the polymerase chain reaction (PCR), we analyzed hind limb skeletal muscle from mice of three age groups (5, 16 and 25 months) for the presence of age-associated mtDNA deletions. We observed multiple mtDNA deletions in all three age groups. Further, the number of deletions detected per mouse increased greatly with advancing age. PMID- 7993928 TI - Platelet MAO-B activity as a marker of behavioural characteristics in dementia disorders. AB - Both low and high platelet MAO-B (pMAO-B) activity is considered an indicator of increased vulnerability in psychopathology. How the activity of this peripheral enzyme can be linked with the sophisticated functions of the central nervous system (CNS) is not clear; in man, evidence exists that the genetic mechanisms determining the size or capacity of the central serotonin system are common to platelet and brain MAO. In the present study pMAO-B activity was evaluated in demented patients suffering from early-onset Alzheimer's disease (AD), late-onset Alzheimer's disease (SDAT), vascular dementia (VD), and controls. In these dementia categories, the relationship between pMAO-B activity and clinical features, and between pMAO-B activity and cerebrospinal fluid (CSF) monoamine metabolites (3-methoxy-4-hydroxyphenyl-glycol, MHPG; 5-hydroxy-indoleacetic acid, 5-HIAA; homovanillic acid, HVA) was also investigated. pMAO-B activity was significantly higher in SDAT patients, compared to controls and AD. Age, as covariate, failed to show any significant effect, and no association was found between pMAO-B activity and CSF monoamine metabolites. The correlation analysis between pMAO-B and neuropsychological scores showed a highly significant positive relationship with GBS-emotional impairment (N = 40, r = 0.72, p < 0.01) in the SDAT group. This result suggests the importance of platelet MAO-B activity as biological marker also in old-age dementias, namely senile dementia of Alzheimer type, where the increased activity of this enzyme might constitute a marker for vulnerability toward behavioural disturbance, i.e., emotional deterioration. PMID- 7993929 TI - Uncovering the synchronization dynamics from correlated neuronal activity quantifies assembly formation. AB - Synchronous network excitation is believed to play an outstanding role in neuronal information processing. Due to the stochastic nature of the contributing neurons, however, those synchronized states are difficult to detect in electrode recordings. We present a framework and a model for the identification of such network states and of their dynamics in a specific experimental situation. Our approach operationalizes the notion of neuronal groups forming assemblies via synchronization based on experimentally obtained spike trains. The dynamics of such groups is reflected in the sequence of synchronized states, which we describe as a renewal dynamics. We furthermore introduce a rate function which is dependent on the internal network phase that quantifies the activity of neurons contributing to the observed spike train. This constitutes a hidden state model which is formally equivalent to a hidden Markov model, and all its parameters can be accurately determined from the experimental time series using the Baum-Welch algorithm. We apply our method to recordings from the cat visual cortex which exhibit oscillations and synchronizations. The parameters obtained for the hidden state model uncover characteristic properties of the system including synchronization, oscillation, switching, background activity and correlations. In applications involving multielectrode recordings, the extracted models quantify the extent of assembly formation and can be used for a temporally precise localization of system states underlying a specific spike train. PMID- 7993931 TI - Reconstruction of equilibrium trajectories and joint stiffness patterns during single-joint voluntary movements under different instructions. AB - A method for reconstructing joint compliant characteristics during voluntary movements was applied to the analysis of oscillatory and unidirectional elbow flexion movements. In different series, the subjects were given one of the following instructions: (1) do not intervene voluntarily; (2) keep the trajectory; (3) in cases of perturbations, return back to the starting position as quickly as possible (only during unidirectional movements). Under the instruction 'keep trajectory', the apparent joint stiffness increased by 50% to 250%. During oscillatory movements, this was accompanied by a decrease in the maximal difference between the actual and equilibrium joint trajectories and, in several cases, led to a change in the phase relation between the two trajectories. The coefficients of correlation between joint torque and angle were very high (commonly, over 0.9) under the 'do not intervene' instruction. They dropped to about 0.6 under the 'keep trajectory' and to about 0.3 under the 'return back' instructions. Under these two instructions, the low values of the coefficients of correlation did not allow reconstruction of segments of equilibrium trajectories and joint stiffness values in all the subjects. The results provide further support for the lambda-version of the equilibrium-point hypothesis and for using the instruction 'do not intervene voluntarily' to obtain reproducible time patterns of the central motor command. PMID- 7993930 TI - Generation of periodic and chaotic bursting in an excitable cell model. AB - There are interesting oscillatory phenomena associated with excitable cells that require theoretical insight. Some of these phenomena are: the threshold low amplitude oscillations before bursting in neuronal cells, the damped burst observed in muscle cells, the period-adding bifurcations without chaos in pancreatic beta-cells, chaotic bursting and beating in neurons, and inverse period-doubling bifurcation in heart cells. The three variable model formulated by Chay provides a mathematical description of how excitable cells generate bursting action potentials. This model contains a slow dynamic variable which forms a basis for the underlying wave, a fast dynamic variable which causes spiking, and the membrane potential which is a dependent variable. In this paper, we use the Chay model to explain these oscillatory phenomena. The Poincare return map approach is used to construct bifurcation diagrams with the 'slow' conductance (i.e., gK, C) as the bifurcation parameter. These diagrams show that the system makes a transition from repetitive spiking to chaotic bursting as parameter gK, C is varied. Depending on the time kinetic constant of the fast variable (lambda n), however, the transition between burstings via period-adding bifurcation can occur even without chaos. Damped bursting is present in the Chay model over a certain range of gK, C and lambda n. In addition, a threshold sinusoidal oscillation was observed at certain values of gK, C before triggering action potentials. Probably this explains why the neuronal cells exhibit low amplitude oscillations before bursting. PMID- 7993932 TI - Temporal variability in a system of coupled mitotic timers. AB - Cell proliferation is considered a periodic process governed by a relaxation timer. The collective behavior of a system composed of three identical relaxation oscillators in numerically studied under the condition that diffusion of the slow mode dominates. We demonstrate: (1) the existence of three periodic regimes with different periods and phase relations and an unsymmetrical, stable steady-state (USSS); (2) the coexistence of in-phase oscillations and USSS; (3) the coexistence of periodic attractors; and (4) the emergence of a two-loop limit cycle coexisting with both in-phase oscillations and a stable steady-state. The qualitative reasons for such a diversity and its possible role in the generation of cell cycle variability are discussed. PMID- 7993933 TI - The influence of limited presynaptic growth and synapse removal on adaptive synaptogenesis. AB - This report continues our research into the effectiveness of adaptive synaptogenesis in constructing feed-forward networks which perform good transformations on their inputs. Good transformations are characterized by the maintenance of input information and the removal of statistical dependence. Adaptive synaptogenesis stochastically builds and sculpts a synaptic connectivity in initially unconnected networks using two mechanisms. The first, synaptogenesis, creates new, excitatory, feed-forward connections. The second, associative modification, adjusts the strength of existing synapses. Our previous implementations of synaptogenesis only incorporated a postsynaptic regulatory process, receptivity to new innervation (Adelsberger-Mangan and Levy 1993a, b). In the present study, a presynaptic regulatory process, presynaptic avidity, which regulates the tendency of a presynaptic neuron to participate in a new synaptic connection as a function of its total synaptic weight, is incorporated into the synaptogenesis process. In addition, we investigate a third mechanism, selective synapse removal. This process removes synapses between neurons whose firing is poorly correlated. Networks that are constructed with the presynaptic regulatory process maintain more information and remove more statistical dependence than networks constructed with postsynaptic receptivity and associative modification alone. Selective synapse removal also improves network performance, but only when implemented in conjunction with the presynaptic regulatory process. PMID- 7993934 TI - Human cancer and gene therapy. PMID- 7993935 TI - Molecular pathology of AIDS-related lymphomas. Biologic aspects and clinicopathologic heterogeneity. AB - A high frequency of lymphoma in human immunodeficiency virus-infected individuals has been reported since the outbreak of the acquired immunodeficiency syndrome (AIDS) epidemic in 1982. AIDS-associated non-Hodgkin's lymphoma (AIDS-NHL) is almost invariably derived from B cells and is classified as high- or intermediate grade NHL, according to the working formulation. Two main histologic types are recognized, including small noncleaved cell lymphoma (SNCCL) and diffuse large cell lymphoma (DLCL). Pre-existing host factors putatively involved in lymphoma development include disrupted immunosurveillance, deregulated cytokine production, chronic antigen stimulation, and infection by Epstein-Barr virus (EBV). These alterations are associated with the development of multiple oligoclonal expansions which correspond to the clinical phase known as persistent generalized lymphadenopathy (PGL). The appearance of a true AIDS-NHL is characterized by the presence of a monoclonal B-cell population displaying several genetic lesions, including monoclonal EBV infection, c-MYC and BCL-6 rearrangements, RAS mutations, p53 inactivation, and 6q deletions. These genetic lesions cluster into two distinct molecular pathways, which specifically associate with the different histologic subtypes of AIDS-NHL, i.e., AIDS-SNCCL and AIDS-DLCL. The presence of distinct genetic pathways for AIDS-SNCCL and AIDS DLCL correlate with a number of clinical features which distinguish these two groups of tumors, including differences in the age of onset, CD4 counts at the time of presentation, time elapsed since HIV infection, and clinical outcome. PMID- 7993936 TI - Acute lymphoblastic leukemia in patients over 59 years of age. Experience in a single center over a 10-year period. AB - We report data of 29 consecutive patients aged 60 years or older with newly diagnosed acute lymphoblastic leukemia (ALL) treated at a single center between 1983 and 1992. Immunophenotyping was performed in 26 patients. According to the immunological classification used at the time of diagnosis, 14 had common-ALL, two had T-ALL, six had null-ALL, three had myeloid antigen-positive ALL with both lymphoid and myeloid markers, and one had B-ALL. One patient died before therapy could be instituted. Twenty-four patients received intensive induction chemotherapy. Nine of these patients died during the first 8 weeks, eight due to infections and one due to liver failure after asparaginase. In 14 of the remaining patients treated intensively, scheduled treatment was discontinued prematurely due to treatment-related toxicity and was replaced by milder chemotherapy. Four patients aged 75-77 years were treated with vincristine and prednisone. Only one patient who completed a whole study protocol survived more than 5 years. Twelve of the 28 patients treated with chemotherapy achieved complete remissions. The median survival was 5 months (range 1-103+). Median survival in patients with CR was 9.0 months. Actuarial survival is 3%. Our data demonstrate a poor prognosis in ALL patients over 59 years of age. The reasons were a high mortality during intensive induction therapy due to toxicity of treatment and a short remission duration. PMID- 7993937 TI - Improvement of hematologic recovery after high-dose intensification using peripheral blood progenitor cells (PBPC) mobilized by chemotherapy and GM-CSF. AB - We have tested the efficiency of GM-CSF to mobilize peripheral blood progenitor cells (PBPC) and evaluated the hematological reconstitution after GM-CSF primed PBPC infusion following myeloablative therapy. Twenty three patients suffering from hematological malignancies were included in this study. Starting 24 hours after completion of a standard dose chemotherapy including vindesine, cyclophosphamide, adriblastine, prednisone, (VCAP), 5 micrograms/kg sub-cutaneous daily dose GM-CSF was given for a median time of 14 days followed by three consecutives cycles of leukapheresis. Fifteen of these 23 patients underwent GM CSF primed-PBPC autotransplantation following high dosed intensification regimen. PBPC collection and hematopoietic recovery were compared with a 15 patients control group who did not receive GM-CSF. No marrow or growth factors were administered after PBPC reinfusion in the two groups. VCAP/GM-CSF mobilization induced significantly higher yields of CFU-GM (3.8 fold) than did VCAP mobilization alone, 19 x 10(4)/kg (2-73) vs 5 x 10(4)/kg (2-27), (p < 0.005). The median number of days to achieve 1.10(9)/l neutrophils, platelet count > 20.10(9)/l and > 50.10(9)/l was significantly lower in the GM-CSF group than in the control group, respectively 13 vs 19 days (p = 0.04), 15.5 vs 27 days (p < 0.02), 19 vs 51 days (p < 0.01). When compared with the control group, transfusion requirements and median of hospital stay were both significantly decreased for the patients receiving GM-CSF primed-PBPC. Our study confirms that infusion of GM-CSF primed-PBPC as a sole source of hematopoietic support improves hematopoietic reconstitution following myeloablative therapy. PMID- 7993938 TI - Phase-II trial with M-CAVe-CEC as a salvage chemotherapeutic regimen for early relapsed or primary refractory Hodgkin's disease. AB - A substantial number of patients with Hodgkin's disease (HD) do not respond adequately to standard therapy. Patients who relapse later than 1 year after completion of treatment have a good chance of achieving a second complete remission (CR). The prognosis of patients with primary refractory HD or relapse within 1 year, however, is poor. The long-term results of autologous bone marrow transplantation (ABMT) in these patients have not yet been established. Therefore, we conducted a phase-II study among 15 patients with primary refractory or early relapsed HD, in which they were treated with a two-drug sequential regimen not cross-resistant with MOPP. The patients received two to six courses of methotrexate, cyclophosphamide, adriamycin, vinblastine, CCNU, etoposide, and chlorambucil (M-CAVe-CEC). Seven patients (47%) achieved a CR, including a patient with additional radiotherapy. Actuarial overall survival was 58 and 41%, respectively, and failure-free survival 38% at 2 and 5 years. Gastrointestinal toxicity was acceptable. Dose reductions were necessary in up to 60% of courses given. These preliminary results suggest that the M-CAVe-CEC regimen may be a more effective salvage regimen as compared with other regimens for primary refractory or early relapsed HD. Larger studies, possibly with hematopoietic growth factors, are required to determine its value in comparison to ABMT. PMID- 7993939 TI - Secretion of phospholipase A2 induced by interactions of human platelets with monocytes. AB - Phospholipase A2 (PLA2) activity was found and measured in the cell-free supernatants of human mononuclear cells (monocytes and lymphocytes) cultured with platelets for 48 h at 37 degrees C. The relative molecular mass of purified, calcium-dependent PLA2 was 14 kD. The amount of PLA2 in the supernatants correlated positively with the number of monocytes and platelets in the cultures. Electron microscopically, direct cell-to-cell interactions of monocytes and platelets were observed. Cultivation of suspensions of human mononuclear cells with platelets in serum-free medium was found to be an efficient way to produce and purify human secretable PLA2. In the release of secretable PLA2 in peripheral blood, the interactions between platelets and monocytes may play a considerable role. PMID- 7993940 TI - Plasma concentrations of total/free and functional protein S are not decreased in systemic lupus erythematosus patients with lupus anticoagulant and/or antiphospholipid antibodies. AB - We conducted an investigation to clarify whether or not the levels of total, free, and functional protein S and C4-binding protein (C4bp) in plasma are decreased in systemic lupus erythematosus (SLE) patients, especially those with antiphospholipid antibody (aPL), which is known to be a causative factor of such complications as habitual abortion and arteriovenous thrombosis. Fifty patients with SLE were recruited as subjects of the study. Serum aPL (anticardiolipin, antiphosphatidyl serine, antiphosphatidyl inositol, and antiphosphatidic acid antibodies) were measured by ELISA. Lupus anticoagulant was determined by a PTT, KCT, and diluted RVVT. Furthermore, plasma concentrations of total, free, and functional protein S and C4bp were measured. There were no significant differences in the mean levels of total, free, or functional protein S and C4bp between aPL-positive, aPL-negative SLE patients, and the healthy controls. From these results, we concluded that the protein S level is not the sole factor causing complications, and that other factor(s) may be involved in the induction of such complications in this clinical setting. PMID- 7993941 TI - Hemophilia A or von Willebrand disease? AB - Seven members of the same family were studied on several occasions due to a history of hemorrhages. The propositus, a 12-year-old boy, his sister, one brother, and their father all had a low plasma factor VIII (FVIII) level. Von Willebrand factor (vWF) activity, vWF multimeric analysis, and vWF factor domain for binding to FVIII were normal in all seven subjects. The sister had a normal 46XX karyotype. The study of two intragenic restriction fragment length polymorphisms (RFLPs) and two closely linked, highly polymorphic extragenic markers showed a phenotypic expression of mild hemophilia A, which suggests that the sister of the propositus is homozygous or compound heterozygous at the hemophilia A locus. She would have inherited two hemophilic genes: one from her carrier mother and the other from her father, a mild hemophiliac. PMID- 7993942 TI - Growth-factor-like substance in amniotic fluid in the rat: effect on the development of fetal colonic goblet cells. AB - Extra- and intrauterine fetuses were studied to explore the effect of amniotic fluid on the development of colonic goblet cells. Significant differences in the density of goblet cells in developing colon were observed during fetal days 19-22 between these two groups, suggesting that amniotic fluid affects the development of the colonic goblet cells, especially during the period between days 19 and 21 when rat fetuses began to swallow amniotic fluid, as demonstrated by injecting India ink into the amniotic cavity. By immunological dot blot analysis, the amniotic fluid and gastric juice from intrauterine fetuses were positive for epidermal growth factor (EGF), whereas maternal abdominal serous fluid and gastric juice from extrauterine fetus were negative for EGF. The present results indicate that the amniotic fluid during late gestation greatly affects the development of the colonic goblet cells in rat fetuses and that the trophic factors for the cells seems to be EGF or an EGF-like substance in the amniotic fluid. PMID- 7993943 TI - The catecholamine sensitivity of adult rats is enhanced after prenatal hypoxia. AB - In this study, the effect of prenatal hypoxia on the catecholamine sensitivity of the offspring of pregnant rats was investigated. The offspring from hypoxic animals showed after treatment with isoproterenol in adult age a distinctly more pronounced decrease of protein content and enzyme activities in heart tissue as well as a significantly higher elevation of enzyme activities in blood plasma as compared with the offspring from normoxic rats. These results suggest a long lasting enhancement of catecholamine sensitivity after prenatal oxygen deficiency. PMID- 7993944 TI - Alteration of maternal growth hormone levels during pregnancy influences both fetal and postnatal growth in rats. AB - To study the effects of exogenous growth hormone (GH) administration to the mother on fetal growth, dwarf rats with an isolated GH deficiency were given daily s.c. injections of GH throughout pregnancy. Fetuses were heavier in GH treated mothers (p < 0.001), and pups from GH-treated mothers continued to grow faster (p < 0.001) than pups from control mothers throughout the postnatal growth period through to weaning. In normal Wistar rats, administration of a potent antiserum to somatostatin to pregnant rats increased the mean birth weight of the offspring (p < 0.01). Administration of GH to the mothers also significantly increased birth weight (p < 0.05), but administration of antiserum to rat GH resulted in a significant retardation of both fetal and placental growth (p < 0.001). These data suggest that maternal GH status is significantly involved in the growth of the fetal rat. PMID- 7993945 TI - Postnatal development of ornithine decarboxylase and polyamines in the mouse kidney: influence of testosterone. AB - The role of ornithine decarboxylase (ODC) and polyamines in kidney growth during the postnatal development of mice and the influence of testosterone were investigated. A marked sexual dimorphism in renal size was evident after the 3rd week of life, corresponding with the rise in circulating testosterone and the increase in renal ODC and urinary excretion of putrescine in male mice. Renal putrescine and spermidine gradually decreased during the first 3 weeks of life and did not correlate with ODC activity. Treatments with alpha difluoromethylornithine, and ODC-specific inhibitor, and the antiandrogen flutamide during weeks 4 and 5 showed that both compounds decreased renal ODC activity but only flutamide impaired kidney growth, suggesting that renal growth in mice is regulated by androgens but is independent of the induction of ODC activity. PMID- 7993946 TI - Influence of disease state on oxygen transport in newborn piglets. AB - Optimally, oxygen delivery (DO2) should be sufficient to provide for adequate oxygen consumption (VO2) while avoiding O2 toxicity. Physiologically a critical level of DO2 has been described, below which decreases in oxygen supply begin to impair VO2, leading to venous hypercarbia and tissue acidosis. We predicted that this critical level would be influenced by factors such as underlying disease state and oxygen needs. Newborn piglets were exposed either to hypoxia (n = 6) or to group-B beta-hemolytic streptococcal sepsis (n = 6). Hemodynamic parameters were measured; DO2 and VO2 were calculated and compared within and between the groups. 'Critical DO2' was defined as the point at which decreases in DO2 began to produce concomitant decreases in VO2. This was observed at 9 ml/kg/min in hypoxic vs. 21 ml/kg/min in septic piglets. The 'critical Vsat' was defined as the venous O2 saturation beyond which tissue acidosis, as defined by base excess, developed. 'Critical VsatS' were 17% for hypoxic vs. 21% for septic animals. In summary, septic newborn piglets had higher critical DO2 and critical Vsat than hypoxic piglets, implying that they became oxygen supply dependent and developed tissue acidosis at higher levels of DO2 and Vsat, respectively. PMID- 7993948 TI - Effect of mode of delivery, parity and umbilical blood gas on first meconium passage in full-term healthy neonates. AB - The various physiologic factors which might influence the time of first meconium passage were studied in 62 healthy full-term newborn infants. Thirty-two babies were born vaginally and 30 by elective cesarean section. Infants born vaginally were more acidotic and passed first stool earlier compared to those born by cesarean section. The same applies to vaginally delivered babies when comparing babies born to primipara and others. Acidosis is a presumed mechanism, and a role of gastrointestinal hormones is suggested to be the possible mediator of increased motility in these babies. PMID- 7993947 TI - Validation of cardiac output measurements with noninvasive Doppler echocardiography by thermodilution and Fick methods in newborn piglets. AB - Since cardiac output measured by the noninvasive pulsed Doppler technique has not been well correlated to results from the invasive thermodilution or Fick methods in neonates, the three methods were evaluated in 6 sedated newborn piglets (age < or = 7 days, weight 1.5 +/- 0.7 kg) in room air and after 10 min of hypoxia. Doppler velocities were measured in the ascending aorta, and the aortic root diameter was measured in early diastole. A Swan-Ganz catheter in the left pulmonary artery sampled mixed venous blood for central venous O2 content and measured cardiac output by thermodilution. Oxygen consumption was measured by the open-circuit technique and used to determine cardiac output by the Fick method. In room air, values obtained by pulsed Doppler, thermodilution and Fick methods (0.270 +/- 0.05, 0.246 +/- 0.05 and 0.241 +/- 0.05 liters/kg/min, respectively) were similar, with a correlation coefficient (r) between Doppler and thermodilution values of 0.89, Doppler and Fick values of 0.82 and thermodilution and Fick values of 0.88. Although hypoxia sometimes produced larger differences between paired values, correlation coefficients remained high (Doppler echocardiography vs. thermodilution, r = 0.96; Doppler vs. Fick methods, r = 0.92; thermodilution vs. Fick method, r = 0.95). The mean +/- SD of the percent difference between values obtained by Doppler echocardiography and thermodilution was 4.2 +/- 14.4% in room air and 12.8 +/- 14.4% in hypoxia, whereas differences in values obtained by Doppler and Fick methods was 6 +/- 14.9% in room air and 14.7 +/- 8.5% with hypoxia.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7993949 TI - Arginine deficiency accompanies persistent pulmonary hypertension of the newborn. AB - Persistent pulmonary hypertension of the newborn (PPHN) is a life-threatening disorder of neonates manifested by vasoconstriction of the pulmonary arteries. Recently, the gas nitric oxide (NO) has been used with some success in the management of infants with PPHN. Exogenous administration of NO selectively dilates the pulmonary vascular bed. NO is naturally synthesized in the body from the amino acid L-arginine. Here we report our findings that infants with PPHN are deficient in arginine and achieve normal or elevated plasma arginine concentrations with intravenous hyperalimentation. We prospectively identified and studied 10 infants with PPHN who were not receiving protein or amino acids for at least 24 h and compared their plasma arginine concentrations to 8 control infants without PPHN given similar nutrition. Plasma arginine concentrations were 32 +/- 14 and 52 +/- 20 mumol/l in infants with PPHN and control infants, respectively (p = 0.02). There were no other statistically significant differences in plasma amino acid concentration for any of the 22 other amino acids determined. Infants with PPHN who were subsequently treated with amino acid infusions had plasma arginine concentrations of 115 +/- 48 mumol/l (mean of ten determinations at 86 +/- 27 h after initiation of intravenous amino acids in five PPHN infants). PMID- 7993950 TI - Hyperbilirubinemia in premature infants: relevance to blood transfusion. AB - The rate of hemolysis of transfused adult red blood cells in the premature circulation may be higher than in the native circulation and produce a significant bilirubin load on the immature liver during the first days of life with consequent hyperbilirubinemia. The association between the transfusion of packed red blood cells and consequent change of serum bilirubin level was evaluated in 35 premature infants with birth weight of < 1,250 g during the first 10 days of life, using the analysis of variance method. There was a significant increase of bilirubin level with a mean of 24.3 mumol/l following packed red blood cells transfusion. Birth weight had a significant negative effect and mechanical ventilation for > 2 days had a significant positive effect on bilirubin levels; however, the changes were of small magnitude. The results of our study indicate that a rise of bilirubin level following blood transfusion to very low birth weight infants during the early neonatal period should be anticipated. PMID- 7993951 TI - Hyperoxia induces interstitial (type I) and increases type IV collagenase mRNA expression and increases type I and IV collagenolytic activity in newborn rat lung. AB - Oxygen toxicity is attributed to the reaction of oxygen metabolites with cellular components leading to cell destruction. Activation of latent human neutrophil interstitial collagenase by reactive oxygen species has been demonstrated. The potential role of collagenases in hyperoxic lung injury has not been investigated. We studied the effect of hyperoxia on newborn rat lung water content, morphology and ultrastructure, interstitial (type I) and type IV collagenase gene expression and type I and IV collagenolytic activity. We observed that hyperoxia causes pulmonary edema, alters newborn rat lung morphology in a sequential manner and produces ultrastructural alterations, induces type I and increases type IV collagenase mRNA expression, and increases type I and IV collagenolytic activity. A role for type I and IV collagenase in hyperoxic newborn lung injury or in the recovery following the injury is proposed. PMID- 7993952 TI - Sequential changes in pulmonary epithelial permeability after birth in term and preterm rabbits. AB - We assessed sequential changes in the permeability properties of the pulmonary epithelium in spontaneously breathing, newborn term (30 days of gestation) and preterm (28 days) rabbit pups, using the rate of pulmonary clearance of 99mTc DTPA (MW = 492) as an index of permeability. In term rabbits, clearance was faster at 1 h of age than at hourly timepoints thereafter (p < 0.05). In preterm rabbits, clearance rates measured from 1 to 5 h after birth were not quite significantly different (p = 0.0519) although the trend to slower clearance with increasing time after birth was significant. When term and preterm rabbits were compared, clearance was similar at 1 h after birth but was faster at both 2 and 3 h in the preterm rabbits (p < 0.05). Pulmonary epithelial permeability appears to be increased in the immediate postnatal period and the duration of increased permeability is longer in preterm rabbits. Because lung water content at birth is greater in the preterm rabbits, we speculate that the permeability changes may be associated with clearance of fetal lung liquid. PMID- 7993953 TI - Elevated production of interleukin-1-beta from alveolar macrophages isolated from newborn rabbits. AB - Alveolar macrophage (AM) production of pro-inflammatory cytokines has been associated with the development of acute and chronic lung injury. However, the role of AM-derived IL-1 beta in the development of bronchopulmonary dysplasia has not been extensively examined. To determine if in vitro production of IL-1 beta by AM is influenced by maturity, cells were isolated by lung lavage from litters of newborn rabbits and from adults. After overnight incubation in serum supplemented medium, newborn AM produced more IL-1 beta than cells from adults. When these AM were then exposed for 2 h to endotoxin in serum-free medium, adult cells increased their IL-1 beta secretion while the newborn cells did not. Newborn AM IL-1 beta response to LPS returned by 24 h. AM from newborn rabbits also demonstrated increased spontaneous production and increased LPS-induced production of IL-1 beta during overnight incubation in serum-free medium. The newborn rabbit AM appears to be up-regulated in its IL-1 beta production compared to the adult. PMID- 7993954 TI - Studies of a neurochemical link between depression, anxiety, and stress from [3H]imipramine and [3H]paroxetine binding on human platelets. AB - We measured platelet [3H]imipramine and [3H]paroxetine binding in patients with major depression (n = 11), dysthymia (n = 9), generalized anxiety (n = 18) and panic disorder (n = 10), and in healthy controls (n = 13). The [3H]imipramine binding capacity (Bmax) was lower in all patient groups; [3H]paroxetine binding was reduced in anxiety disorders, however, decreases in depression and dysthymia were not significant. There were no differences in the affinity constant (Kd) for either radioligand. We also examined the effects of examination stress on platelet binding in medical students. Compared to after vacation, when binding was similar to controls, [3H]imipramine (n = 19) and [3H]paroxetine (n = 14) Bmax values were significantly decreased during examinations and similar to patient values. Examinations were also associated with an increase in plasma cortisol levels. These findings suggest that there is a neurochemical link between depression, anxiety, and stress, and that disturbances in neurochemical functioning may be associated with specific symptomatology, independent of psychiatric diagnosis. PMID- 7993955 TI - Is platelet imipramine binding reduced in depression? A meta-analysis. AB - Although it has been suggested that decreased platelet imipramine binding may be a putative biological marker of depressive illness, a number of studies have not confirmed this finding, including a recent multicenter investigation by the World Health Organization (Mellerup and Langer 1990). We performed a meta-analysis of published reports on imipramine binding in groups of depressed and healthy control subjects and found that there was a highly significant decrease in Bmax (maximal binding) values in the depressed subject groups, which was even greater among those who had been free of medication for 4 weeks at the time of investigation. This finding remained highly significant even when only high affinity binding studies (Kd < 1 nmol/L) were considered, although the absolute size of this decrease was smaller. PMID- 7993956 TI - Attenuation of hormone responses to the 5-HT1A agonist ipsapirone by long-term treatment with fluoxetine, but not desipramine, in male rats. AB - The present study had two objectives: (1) to provide information on neuroendocrine challenge tests that can lead to diagnostic tests in humans; and (2) to confirm our previous observation that chronic fluoxetine selectively inhibits serotonin (5-HT1A) receptor function. We determined the effect of chronic fluoxetine and desipramine (DMI) on the hormone response to ipsapirone, a 5-HT1A agonist and a potential anxiolytic drug. Ipsapirone increased oxytocin, adrenocorticotropic hormone (ACTH), corticosterone, and prolactin, but not renin or vasopressin concentrations in plasma. Chronic fluoxetine, but not DMI, significantly inhibited the effect of ipsapirone on plasma oxytocin, ACTH and corticosterone concentrations. Chronic fluoxetine also reduced the Bmax for 3H-8 hydroxy-2-(dipropylamino) tetralin (3H-8-OH-DPAT) labelled 5-HT1A receptors in the midbrain. Neither antidepressant altered the density or affinity of 5-HT uptake sites. In conclusion, the present results confirm our previous results using 8-OH-DPAT as a challenge, and suggest that chronic 5-HT uptake inhibition results in adaptive changes leading to decreased function of the 5-HT1A receptor system. Finally, because ipsapirone may be administered to humans, it might be usable to evaluate 5-HT1A receptor function in depressed patients. PMID- 7993957 TI - The 5-HT3 antagonist, BRL 46470 does not attenuate m-chlorophenylpiperazine (mCPP)-induced changes in human volunteers. AB - Results from animal studies have suggested that serotonin (5-HT) antagonists acting on the 5-HT3 receptor may have anxiolytic properties. We have assessed whether pretreatment with the 5-HT3 receptor antagonist BRL 46470 (1 mg orally) attenuates the increase in anxiety induced in healthy volunteers by intravenous infusion of m-chlorophenylpiperazine (mCPP: 0.08 mg/kg over 2 min). In this double-blind placebo-controlled crossover study in 12 healthy men who were volunteers, infusion of mCPP caused significant increases in self-ratings for the psychological and physical symptoms of anxiety, for the symptoms of panic attack, and in the plasma levels of cortisol and prolactin, with four subjects (33%) experiencing an mCPP-induced "panic attack." Pretreatment with BRL 46470 did not attenuate any of these mCPP-induced changes. These results do not support suggestions from animal studies that 5-HT3 receptor antagonists can attenuate mCPP-induced anxiety, although it is conceivable that a different dose of BRL 46470 may have been effective. PMID- 7993959 TI - Serotonin and alcohol intake, abuse, and dependence: clinical evidence. AB - A large body of literature has emerged concerning the role of the neurotransmitter serotonin (5-hydroxytryptamine, or 5-HT) in the regulation of alcohol intake and the development of alcoholism. Despite the wealth of information, the functional significance of this neurotransmitter remains to be fully elucidated. This paper, part one of a two-part review, summarizes the available clinical research along two lines: the effects of alcohol on serotonergic functioning and the effects of pharmacological manipulation of serotonergic functioning on alcohol intake in normal (nonalcohol dependent) and alcohol-dependent individuals. It is concluded that considerable evidence exists to support the notion that some alcoholic individuals may have lowered central serotonin neurotransmission. PMID- 7993958 TI - Acute d-amphetamine challenge in schizophrenia: effects on cerebral glucose utilization and clinical symptomatology. AB - The effects of d-amphetamine (0.5 mg/kg orally) on regional cerebral glucose utilization were measured with positron emission tomography (PET) in 17 schizophrenics (along with a placebo-control group of an additional six schizophrenic patients). The acute d-amphetamine challenge tended to decrease glucose utilization throughout much of the brain, with a regional effect that was statistically significant in the left temporal cortex. There was no apparent relationship between the effects of amphetamine-induced changes in regional cerebral metabolism and psychotic symptom exacerbation. An exploratory analysis suggested that features characteristic of Crow's type II syndrome were significant predictors of cerebral hyporesponsivity to stimulant challenge, however. PMID- 7993960 TI - Clozapine treatment of nonpsychotic rapid cycling bipolar disorder: a report of three cases. PMID- 7993961 TI - Sleepiness and sleep onset REM periods in the absence of clinical symptomatology. PMID- 7993962 TI - Reduced prolactin response to fenfluramine challenge in personality disorder patients is not due to deficiency of pituitary lactotrophs. PMID- 7993963 TI - Pain thresholds are not elevated in trichotillomania. PMID- 7993964 TI - Clozaril--saving lives. PMID- 7993965 TI - Punding on levodopa. PMID- 7993966 TI - Transfer of shuttle vectors containing Bacillus thuringiensis toxin gene into wild-type B. cereus, B. brevis and B. subtilis by electroporation. AB - Gram positive and negative bacterial shuttle vectors carrying Bacillus thuringiensis (B.t.) toxin gene were introduced by electroporation into wild-type Bacillus cereus, B. brevis and B. subtilis. The transformation efficiencies for these bacteria were around 10(1)-10(4) transformants per micrograms DNA based on the numbers of neomycin- and ampicillin-resistant colonies produced. The structure of the transferred plasmids proved identical with the original ones both in size and restriction pattern. Toxicity assays showed that the transformants gave a mortality of 90-100% against caterpillar of Heliothis assulta, indicating that the gene function was not changed by electroporation. PMID- 7993967 TI - Effect of 5' non-coding region on expression of LT-B gene. AB - The different construction of mRNA 5' non-coding region may affect gene expression. To improve gene expression levels, we constructed recombinant plasmids with different nucleotide composition of the 5' non-coding region which direct the synthesis of human toxicogenic E. coli heat-labile enterotoxin B subunit coded by LT-B gene under the control of the PRPL tandem promoter of vector pBV220. These recombinants were expressed in E. coli HB101 and DH5 alpha, respectively. The results show that the expression levels of LT-B gene with two tandem SD sequences upstream from the initiation codon are lower than those with only one SD sequence and translation coupling can improve the expression levels; the different SD sequences can affect the expression of LT-B gene a little. The SD sequence of LT-B gene itself may be better for expression than that of the vector pBV220; the length of 5' non-coding region in the recombinants harboring only one SD sequence has no effect on the expression of LT-B gene; the expression of LT-B gene in HB101 is higher than that in DH5 alpha. PMID- 7993968 TI - Cloning and high level expression of gene encoding ES antigen from Trichinella spiralis muscle larvae. AB - The partial structure gene encoding ES antigen derived from Trichinella spiralis (TSP) muscle larvae was cloned, characterized, and expressed in E. coli. The target DNA (0.7 kb) was directly obtained from the TSP total RNA by using RNA PCR technique. Based on the analysis with the RE digestion, the fragment was cloned into the fusion expression vector pEX31C. It was shown that a kind of 37kDa fusion protein was expressed in E. coli containing the recombinant plasmid by SDS PAGE electrophoresis. The expressed protein was over 22% of the total cell protein, and it was aggregated in the form of inclusion bodies in E. coli. The purified protein could be recognized in ELISA both by sera from swine-infected with TSP and by the monoclonal antibody against TSP. These findings suggest that the recombinant protein is a potentially valuable antigen both for immunodiagnosis and vaccine development of trichinellosis. PMID- 7993969 TI - High-level expression of staphylococcal nuclease A in Escherichia coli. AB - The staphylococcal nuclease A gene has been successfully cloned and overexpressed in E. coli under the transcriptional control of the bacteriophage lambda PRPL promoters regulated by the temperature sensitive repressors. The SDS-PAGE analysis demonstrates that the nuclease A is produced to the extent of as much as 60% of the total cellular protein. The N-terminal analysis of the nuclease A shows that the amino terminal formyl methionine residue of the enzyme is precisely processed. The recombinant nuclease A with full activity is finally obtained after appropriate solubilization--denaturation and renaturation treatment. The conformational identity of the renatured nuclease A in different conditions is also studied by using hydrophobic interaction chromatography on a phenyl-superose HR5/5 column. PMID- 7993971 TI - Hypocotyl protoplast culture in Brassica napus L. AB - Protoplasts were isolated from the hypocotyls of two oilseed rape (Brassica napus L.) cultivars, Yunbei 2 and Ningyou 7. Light treatment during seed germination could apparently increase their cell division frequency. The purified protoplasts were cultured with three different methods. The method called "agarose island" was found superior to two others ("thin liquid layer" and "agarose solid layer"). The protoplasts cultured in the "agarose island" divided more rapidly and developed into calli more frequently. Shoot regeneration occurred soon after the transfer of protoplast-derived calli onto the differentiation medium. Individual shoots were rooted on the rooting medium. Whole plants were transplanted into pots, and grew well in the phytotron. The "agarose island" method might be suitable for genetic transformation of protoplasts because the liquid medium surrounding the "island" could be conveniently replaced without strong disturbing the microenvironment of protoplasts plated. PMID- 7993970 TI - Transformation of Solanum dulcamara protoplasts and regeneration of transgenic plants. AB - We have achieved successful transformation of Solanum dulcamara protoplasts by direct DNA uptake and regeneration of transgenic plants. The plasmids pDW2 carrying CAT gene and pCaMVNEO carrying NPTII gene were used. The electroporation voltage was 1500 V, which gave a field strength of 1500 V/cm with a time decay constant of 59.4 sec. The concentration of plasmid was 20 micrograms/2 x 10(6) protoplasts. Under these conditions, a very high transformation efficiency was obtained, with relative transformation frequency being up to 12.4% and absolute transformation frequency 2.4 x 10(-4). The activity of NPTII was detected in 75% of the kanamycin resistant calli and all of the plants regenerated from resistant calli. Southern blot analysis showed that the DNA sequence of NPTII gene derived from pCaMVNEO plasmid existed in the transformed plants of S. dulcamara. PMID- 7993972 TI - Synthesis and cloning of the human lysozyme gene. AB - The human lysozyme is an enzyme with potential importance in clinical and industrial application. Owing to the limitation of its natural resource, we are making an attempt to produce the enzyme with the aid of recombinant DNA technology. Twenty-four segments with length ranging from 26 to 38 nucleotides were chemically synthesized by solid phase. The oligonucleotides were joined to form DNA duplexes by two different ligation methods. The entire gene covers a start signal ATG and a BamHI restriction site at its 5' end, and two stop signals TAA TGA and a SphI restriction site at its 3' end, besides the structural gene of human lysozyme. The synthetic gene was cloned into vector M13. The positive colonies were confirmed by dot-blot hybridization and analysis by restriction enzymes. The DNA sequence of the cloned enzyme gene was proved to be correct by M13 dideoxynucleotide chain termination method. The study on gene expression is under way. PMID- 7993973 TI - Plasmid transfer from Escherichia coli to coryneform bacteria by conjugation. AB - The mobilizable shuttle plasmids pXZ911, pBZ51, pBZ52, carrying the Mob site and replication origin of the Corynebacteria plasmid pXZ10145, were constructed. In E. coli S17-1, they can be transferred to coryneform bacteria C. glutamicum ATCC13032, C. glutamicum ATCC21543, C. pekinense B3, C. pekinense AS1.299, C. herculis B43, B. flavum ATCC14067 by conjugation and the transfer frequencies are 9 x 10(-5), 1 x 10(-4), 8.5 x 10(-5), 2.3 x 10(-4), 6 x 10(-4), 2.9 x 10(-5), respectively. This plasmid transfer system, which is convenient and highly effective, should greatly facilitate the basic research and optimization of amino acid genetic engineering in coryneform bacteria and related species. PMID- 7993974 TI - Statistic method for determining the fusion-recombination of cellulase genome. AB - A hypothesis was proposed based on cellulase synergism and multiple variable statistics that the experimental value of N strains out of total fusants from the same cell fusion pool, Aspergillus niger x Trichoderma reesei, could be a sample for the definite fusion cross due to the independence and random of DNA recombination. It could be reduced if fusion recombination happened by analyzing the sample with the provided computer program selected 40 strains of about 2000 fusants of A. niger x T. reesei were analyzed under this procedure as an example and was showed that was effective method on guiding cellulase breeding. PMID- 7993975 TI - Cancer and obesity, nutrition and hormones? PMID- 7993976 TI - Pharmacological aspects of appetite: implications for the treatment of obesity. AB - The properties of an ideal weight-reducing drug would be to produce a sustained decrease in body fat, to oppose the recidivism in obese patients and to improve compliance to dietary requirements. More specifically the drug would have to decrease hunger, be active in the long term, preferably produce no tolerance or rebound effects, and prevent any decrease in basal metabolic rate. Moreover, the drug should reduce the intake of dietary fat which is now regarded as a major cause of weight gain (and regain) [14]. Can this be achieved? Can drug-induced appetite control be used to combat obesity? Some drugs have already demonstrated a capacity to adjust appetite so as to produce significant improvements in the pattern of eating and the control of body weight. What mechanisms are responsible for such an action and how can new drugs be developed so as to advance the pharmacological control of appetite? PMID- 7993977 TI - Physical activity and obesity. AB - Obesity is a major public health problem. Secular increases in the prevalence of obesity appear to be paralleled by decreases in physical activity. Although physical activity and weight are associated, the exact nature of the relationship remains uncertain. Research strongly suggests that exercise is a critical component of any program for weight control and health improvement. Potential mechanisms linking exercise and weight are discussed. For some persons, the health improvement derived from increased activity may not depend on weight loss. Modest levels of activity may be sufficient to achieve both the weight and health benefits of exercise. PMID- 7993978 TI - Obstructive sleep apnea syndrome: a frequent complication of obesity. AB - Obstructive sleep apnea syndrome (OSAS) is a major health problem, not only because of its consequences in terms of morbidity and mortality, but also because of its social impact in the form of car accidents and industrial accidents. These facts stress the necessity of screening OSAS among the population, particularly in patients suffering from obesity or hypertension, diseases frequently associated with OSAS. This review will focus on the epidemiology and the pathophysiology of this syndrome, its clinical features with a view to screening OSAS, and the main examination used to confirm the diagnosis. The management of OSAS will be discussed. PMID- 7993979 TI - Risk factors for obesity in young adults: Hispanics, African Americans and Whites in the transition years, age 16-28 years. AB - Previous studies have suggested that late adolescence may represent a critical period in the development of lifelong obesity, but representative prospective studies in this age group are lacking. The analytic cohort consisted of a representative sample from the United States of 11,591 Hispanic, African American, and white youths interviewed as part of the National Longitudinal Survey of Youth. Significant differences in obesity measures were observed among the six race-sex groups. Compared to whites of the same sex, the prevalence of obesity in 1981 was significantly higher among Hispanic males (12.0 vs 8.6%, P < 0.05) and African American females (14.2% vs 7.3%, P > 0.001) and lower among African American males (6.4% vs 8.6%, P > 0.005). Five-year cumulative incidence of obesity (1981-1986) was highest in Hispanic males, Hispanic females and African American females. Among those ages studied both in 1981 and in 1986, a secular trend towards increased prevalence of obesity was observed over the five year period (10.6% in 1981, 13.6% in 1986, P > 0.0001). Multivariate analyses failed to identify behavioral or sociodemographic factors that operated similarly in all race-sex groups. PMID- 7993980 TI - Awakenings to the pathogenicity of urease and the requirement for continuous long term therapy. AB - Urease is an enzyme found in plants and bacteria, but not mammals. It catalyzes the conversion of urea to carbon dioxide and ammonia. Ammonia shortens the life span of cells; and higher concentrations cause tissue necrosis and cytolysis. Twenty percent of total body urea is converted to ammonia by bacterial urease in the colon. Small injections of urease immunize animals by producing antiurease, a gamma globulin, which inactivates urease. Immunization eliminates the colonic conversion of urea to ammonia. Injection of urease produces ammonia intoxication making immunization hazardous. Although previously impossible, a non enzymatic urease antigen was synthesized by covalently bonding jack bean urease with glutaraldehyde. This antigen stimulated the production of antiurease that inactivates native urease. Helicobacter pylori, a potent urease producer, has been implicated in peptic ulcer, gastritis and other inflammatory bowel lesions. The pathogenicity of H pylori is dependent on its urease production. Immunization to urease can render H pylori non pathogenic. Cirrhotics develop encephalopathy and hyperammonemia because their livers fail to convert all the ammonia in portal venous blood to urea and collaterals develop by passing the liver. Colonic ammonia increases the turnover rate of colonic mucosa. Ammonia absorbed into the portal venous system is transported to the liver where it is reconverted to urea. Absorbed ammonia adversely influences liver function. Infections with urease producing organisms destroy the renal parenchyma and produce struvite stones. Urease immunization aids colonic healing and prevents uremic colitis. Absorbed ammonia is a noxious influence on the liver. Animals immunized to urease regenerate the liver faster and are less susceptible to hepatotoxins. Immunization to urease ameliorates cirrhosis. Proteus and other urease producers become non toxic and do not damage the renal parenchyma. Urease is responsible for the pathogenicity of infections with urease producing organisms. Immunization to urease renders urease producing organisms non pathogenic. PMID- 7993981 TI - CV 205-502 in the treatment of tumoral and non-tumoral hyperprolactinemic states. AB - CV 205-502 (octahydrobenzol[g]quinoline), a non-ergot dopamine agonist drug, was administered to 40 patients with hyperprolactinemic syndrome: 16 patients with macroprolactinoma, 14 with microprolactinoma and 10 with non-tumoral hyperprolactinemia. Twenty-four out of 40 patients had previously been treated by surgery and/or bromocriptine, with variable results. All had gonadal dysfunction and 22 patients had galactorrhea. Eight patients with macroprolactinoma had defects of the visual field. Pre-treatment serum PRL levels ranged from 60 to 2050 micrograms/l. The daily dose of CV 205-502 used in this trial ranged from 0.075 to 0.600 mg. After 6-12 months of treatment, serum PRL level decreased in all the patients reaching normoprolactinemia in 31 of them (77.5%) who demonstrated restoration of menses and disappearance of galactorrhea. The remaining nine patients (22.5%) had only a decrease of PRL levels without reaching normoprolactinemia and without any clinical effect. In 12 out of 16 patients with macroprolactinoma not previously surgically treated, a significant tumor shrinkage was shown by means of Computed Tomography and/or Magnetic Resonance Imaging. The disappearance of visual defects was obtained in four out of eight patients. CV 205-502 was tolerated satisfactorily: mild side-effects occurred in four patients in the first week of treatment and spontaneously disappeared, whereas six patients (15%) needed to withdraw the therapy after 6 months because of side-effects. In conclusion CV 205-502 is a potent and well tolerated drug in the treatment of tumoral and non-tumoral hyperprolactinemic states and is an effective alternative to other dopamine agonists in use today. PMID- 7993982 TI - Percutaneous absorption of diclofenac in healthy volunteers after single and repeated topical application of diclofenac Emulgel. AB - The percutaneous absorption of diclofenac was studied in ten healthy volunteers treated with Emulgel containing 1.16% diclofenac diethylammonium for 8 d as follows: a single application of 5 g Emulgel on days 1 and 8, and two applications d-1 on days 2-7. Plasma concentration profiles of unchanged diclofenac and urinary concentrations of total diclofenac and metabolites (sum of free and conjugated) were determined. High inter-individual variations in plasma and urine data were recorded, due probably to the permeability and the hydration of the skin. Steady state was reached after 2 d of twice-daily administration. Plasma concentrations were low but remained in the range 10-50 nmol L-1 over the full day for most of the subjects, indicating prolonged absorption from the application site. PMID- 7993983 TI - The absence of a pharmacokinetic interaction between aspirin and the angiotensin converting enzyme inhibitor benazepril in healthy volunteers. AB - Potential effects of the coadministration of single doses of aspirin (325 mg) and of benazepril hydrochloride (20 mg) on the pharmacokinetics and the metabolism of these two drugs were evaluated in 12 healthy subjects. Plasma concentration profiles of benazepril, its active metabolite benazeprilat, and total salicylic acid were determined together with urinary excretion of benazeprilat, salicylic acid, salicyluric acid, and salicylate glucuronides. Almost superimposable plasma profiles of benazepril, benazeprilat, and total salicylic acid were achieved with the drugs given alone and concomitantly. The coadministration of benazepril hydrochloride and aspirin did not modify the pharmacokinetics or the metabolism of the two drugs. PMID- 7993984 TI - The effect of colestipol and cholestyramine on ibuprofen bioavailability in man. AB - The purpose of this study was to determine whether a concomitant single oral dose of one of the anion exchange resins colestipol hydrochloride (10 g) or cholestyramine (8 g) administered with ibuprofen (400 mg) would alter the bioavailability of this non-steroidal anti-inflammatory agent. The study was performed according to a randomized three-way crossover design in six healthy male volunteers. After dosing, serial blood samples were collected for a period of 10 h. Plasma harvested from blood was analysed for ibuprofen by a sensitive high-performance liquid chromatographic method. There were no significant differences between colestipol treatment and control for peak plasma concentration (Cmax), time to peak concentration (Tmax), area under the plasma concentration-time curve (AUC), mean residence time (MRT), elimination rate constant (Kel), or elimination half-life (t1/2). Cholestyramine treatment resulted in a significant decrease in AUC (26%, p < 0.05) and Cmax (34.4%, p < 0.01) and a significant increase in Tmax (80%, p < 0.01) and MRT (20.2%, p < 0.05). Cholestyramine administration showed no significant effect on the Kel and t1/2 values. A significant correlation was obtained between the increase in MRT and the increase in Tmax. The confidence intervals (90%) of the mean values of the pharmacokinetic parameters (AUC0-infinity and Cmax) for the colestipol: control ratio were well within the acceptable range of 100 +/- 20, whereas those for the cholestyramine: control ratio were outside it. Colestipol treatment was found to be bioequivalent to the control treatment by Schuirmann's two one-sided t tests, while cholestyramine treatment was found to be bioinequivalent.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7993985 TI - A comparison of population and standard two-stage pharmacokinetic analyses of vigabatrin data. AB - Vigabatrin (VGB), an irreversible inhibitor of GABA, is being developed as an add on therapy for uncontrolled complex partial seizure. A single-dose study was conducted in three groups of subjects with normal, mild-to-moderate, and moderate to-severe renal impairment to examine the effect of renal function on the pharmacokinetics of VGB. Serial blood samples were collected up to 60 h following a single 750 mg oral dose of VGB for the quantitation of drug concentrations. The plasma VGB concentration-time data were analyzed by mixed-effects modeling to estimate population pharmacokinetic parameters and to identify any significant demographic covariates. The parameters of VGB were also calculated by standard two-stage techniques and then compared to the results obtained using the mixed effects analysis. Population VGB plasma concentration-time profiles were best described by a two-compartment model with zero-order absorption. Creatinine clearance was observed to significantly affect the oral clearance of VGB (p < 0.05), i.e. a linear increasing relationship existed between the two variables. Other demographic factors had no influence on VGB pharmacokinetics. There were agreements in the oral clearance, apparent volume of distribution during elimination, and half-life estimates calculated by both methods. In addition, the conventional technique identified a linear relationship between oral and creatinine clearances. In summary, mixed-effects modeling of serial vigabatrin data validated results determined by the standard two-stage technique. PMID- 7993986 TI - The penetration of amphotericin B from an Intralipid formulation into fibrin loci in a rabbit model of candidiasis. AB - The kinetics of amphotericin B (AMB) concentrations in plasma and interstitial fluid were studied in an experimental model of Candida albicans infection in rabbits. Rabbits were infected by subcutaneously implanted fibrin clots containing the yeast. Three groups of five rabbits received a 4 mg kg-1 AMB infusion. AMB (Fungizone) was dissolved in 5% glucose (group I) or in 20% Intralipid at a final concentration of 1.5 (group II) or 3 mg mL-1 (group III). AMB was measured by liquid chromatography in plasma and in trypsin-dissolved fibrin clots up to 72 h after the infusion. No significant differences in AMB plasma and interstitial-fluid concentration kinetics between the three modes of administration were found. AMB penetration into fibrin clots was slow, with no significant differences between treatments. Thus, formulation of AMB in Intralipid does not modify either the drug's interstitial or plasma kinetics at equivalent doses. PMID- 7993987 TI - Relative bioavailability of four controlled-release nifedipine products. AB - Four controlled-release nifedipine products were investigated in two clinical studies. In study 1, 22 healthy male volunteers took part in an open, multiple dose, randomized, crossover study to determine the relative bioavailability of two 10 mg controlled-release nifedipine tablets (Adalat Retard, Bayer), administered 12 hourly, and one 20 mg controlled-release nifedipine tablet (Adalat Retard, Bayer) administered 12 hourly. In study 2, 24 healthy male volunteers took part in an open, multiple-dose, randomized, three-period, crossover study to determine the relative bioavailability of (i) two 30 mg nifedipine gastro-intestinal therapeutic system (GITS) tablets (Adalat XL, Bayer) administered once daily; (ii) one 60 mg nifedipine GITS tablet (Adalat XL, Bayer) administered once daily; and (iii) one 20 mg plus one 10 mg nifedipine controlled release tablet (Adalat Retard, Bayer), administered 12 hourly. In both studies detailed pharmacokinetic data, in particular with respect to the controlled release characteristics of the different formulations, were collected. Results of both studies indicate that all nifedipine products investigated are bioequivalent with respect to the extent of absorption of nifedipine. The nifedipine GITS products (Adalat XL) have better controlled-release properties than the Adalat Retard product, and are suitable for once-a-day administration. PMID- 7993988 TI - Variability in absorption lag time of pyridoxal phosphate under fasting and pre- and post-meal conditions. AB - Inter-individual variations in the absorption lag time of pyridoxal phosphate were determined after administration of an enteric-coated tablet (EC) or a plain capsule (PC) to 113 healthy volunteers under fasting, pre-meal, and post-meal conditions. The absorption lag time of pyridoxal phosphate was assessed from the urinary excretion of 4-pyridoxic acid after administration of EC and PC. Significantly larger lag times after administration of both formulations were observed under post-meal conditions than under pre-meal conditions (0.477 +/- 0.315 h versus 0.081 +/- 0.086 h for PC and 1.995 +/- 1.345 h versus 1.064 +/- 1.327 h for EC), indicating that the mean gastric emptying rates of both a solution and a tablet were delayed after food intake. The lag time for PC showed little inter-individual variation with (0-1.2 h) or without food (0-0.25 h), whereas that for EC showed markedly large inter-individual variation, from 0.25 to 2.63 h (median, 1.5 h) in the fasting condition, from 0.25 to > 5.5 h (median 0.25 h) under pre-meal conditions, and from 0.25 to > 5.5 h (median 1.25 h) under post-meal conditions. The effect of food on the gastric emptying rate of a solution appears to be almost uniform, whereas that for a tablet is so unpredictable that a reliable absorption rate for an enteric-coated tablet cannot be expected, particularly under pre- and post-meal conditions. PMID- 7993990 TI - Bioequivalence of pyrantel pamoate dosage forms in healthy human subjects. AB - Drugs that are largely restricted to the gastro-intestinal tract (GIT) for their therapeutic efficacy and that are not substantially absorbed into the body are usually inadequately studied in terms of systemic bioavailability. The possibility of systemic effects requires that bioavailabilities be studied to ensure against enhanced toxicity resulting from formulation differences. Pyrantel pamoate falls into this category. High-performance liquid chromatography was employed in this study to determine plasma levels of pyrantel in nine healthy human subjects after administration of tablet and suspension dosage forms. Mean peak plasma concentrations of 37.56 +/- 9.37, 35.89 +/- 8.94, and 36.22 +/- 10.10 ng mL-1 were obtained following administration of 750 mg pyrantel pamoate in three different formulations. The mean tmax values were 2.02 +/- 0.12, 2.05 +/- 0.356, and 2.05 +/- 0.339 h respectively for the above dosage forms; the respective AUC0-9 values were 81.01 +/- 12.97, 94.59 +/- 17.18, and 101.47 +/- 19.59 h ng mL-1. There was no statistically significant difference between the bioavailabilities of the dosage forms tested. Large inter-subject variations were observed. One subject experienced abdominal discomfort and one experienced dizziness. It was not possible to clearly correlate individual variations in absorption with the observed adverse effect because the number of incidents was low (two out of 27 treatments). PMID- 7993989 TI - The influence of food on the disposition of the antiepileptic oxcarbazepine and its major metabolites in healthy volunteers. AB - The effect of food on the pharmacokinetics of the antiepileptic oxcarbazepine (OXC) was investigated in healthy volunteers. Six healthy male volunteers were treated with single peroral doses of 600 mg of oxcarbazepine (Trileptal) after overnight fasting or a fat- and protein-rich breakfast. Mean (+/- SD) areas under the plasma concentration-time curves (AUC) of the major component in plasma, the active monohydroxy metabolite (MHD), which is responsible for the therapeutic effect in man, were 672 (25) mumol L-1 h when given to the fasted volunteers and 780 (31) mumol L-1 h (p = 0.042) when given after a substantial breakfast. Mean (+/- SD) maximum concentrations (Cmax) were 25.5 (4.8) mumol L-1 when given to the fasted volunteers and 31.4 (5.3) mumol L-1 (p = 0.025) when given after breakfast. Thus, the average AUC was increased by 16% and Cmax by 23% when oxcarbazepine was given with food. The times at which Cmax was reached (tmax) as well as the terminal half-lives were not influenced by concomitant intake of food. The tolerability was the same whether oxcarbazepine was given before or after food in healthy volunteers. The slight effect of food on the kinetics of oxcarbazepine should be of little therapeutic consequence. PMID- 7993991 TI - Time to abandon nonionic contrast. PMID- 7993992 TI - Contrast nephrotoxicity. AB - Iodinated contrast media have some nephrotoxic potential but rarely cause significant renal failure in patients with normally functioning kidneys. Patients with existing renal impairment, with or without diabetes, those with current congestive heart failure of Class III or IV, those with reduced effective arterial volume (e.g., nephrotic, cirrhotic), or those receiving drugs that may impair renal function or increase contrast nephrotoxicity are at higher risk. Contrast nephrotoxicity may be clinically important in patients with other factors simultaneously affecting the renal response to contrast or in whom acute renal failure would seriously affect prognosis. The pathogenesis of contrast nephrotoxicity probably involves a combination of direct tubular toxicity and renal ischemic injury. Knowledge of the pathogenetic pathways is accumulating and is leading to the discovery of rational specific prophylactic measures to reduce the burden of nephrotoxicity. After the efficacy of these measures has been established, they should be considered for use in patients at high risk. Existing data indicate a limited role for the newer low-osmolality media for the prevention of nephrotoxicity. PMID- 7993993 TI - Interactions of neutrophils with epithelial cells: lessons from the intestine. AB - Active inflammatory processes in organs lined by columnar epithelial cells are often characterized by abundant neutrophil migration. To reach an epithelial surface, neutrophils must leave the vasculature and cross the interstitium where signals may be generated that influence migration and/or epithelial function. Subsequently neutrophils migrate across epithelial linings by impaling intercellular junctions between epithelial cells and, in doing so, diminish the ability of epithelial linings to serve as a barrier. Decreased barrier function brought about by neutrophil migration across epithelia appears to be a reversible process after the removal of the chemotactic stimulus. The molecular events underlying neutrophil-epithelial interactions are at present poorly understood. With recent information regarding neutrophil-endothelial interactions, it has been possible to better understand issues of neutrophil interactions with epithelial cells. In general, there appear to be different rules governing the interaction of neutrophils with endothelial cells as compared with epithelial cells. Neutrophil migration across endothelial monolayers involves a series of at least three steps, each regulated by glycoproteins expressed on the cellular surface. In considering neutrophil-epithelial interactions, the single common denominator is the requirement for surface expression of neutrophil beta 2 integrins, and specifically CD11b/18, as shown by functional inhibition through the use of antibodies to neutrophil beta 2 integrins and the use of neutrophils from patients lacking the beta-chain of this integrin. An understanding of the regulation of neutrophil-epithelial interactions, although in its infancy, appears to involve inflammatory cytokines. Recent in vivo evidence suggests that interferon-gamma production at the level of the intestine may correlate with the regulation of neutrophil-epithelial interactions in vitro by interferon-gamma. Finally, considerable evidence exists that neutrophils may contribute significantly to fluid transport during inflammatory diseases such as secretory diarrhea. When placed in contact with epithelial monolayers, activated neutrophils bring about the transport of ions, with concomitant water loss across epithelial surfaces. This transport process brought about by the presence of neutrophils is generated by a metabolite produced and secreted from neutrophils. This metabolite was originally termed neutrophil-derived secretagogue and has recently been identified as 5'-AMP. The mechanism of 5'-AMP action on epithelial cell ion transport is discussed. PMID- 7993994 TI - Myoglobinuric acute renal failure in a cardiac transplant patient taking lovastatin and cyclosporine. AB - Acute renal failure can occur in cardiac transplant patients for a variety of reasons. A case of a patient who developed acute renal failure secondarily to drug-induced rhabdomyolysis is reported. The literature regarding acute renal failure and lovastatin and other 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors is reviewed. The potential mechanisms of myoglobinuria and nephrotoxicity and the therapeutic implications are discussed. PMID- 7993995 TI - COL4A5 deletions in three patients with Alport syndrome and posttransplant antiglomerular basement membrane nephritis. AB - Mutations in the COL4A5 gene encoding the alpha 5 chain of Type IV collagen were identified in three men with Alport syndrome and posttransplant antiglomerular basement membrane (GBM) nephritis by the use of Southern analysis, polymerase chain reaction amplification of genomic DNA, and reverse transcription and amplification of lymphocyte RNA. Two related patients (M.C. and J.M.) exhibited deletion of COL4A5 beginning in the 5'-most portion of the gene and extending through the 3' untranslated region, whereas the third patient (J.E.) had an intragenic deletion encompassing Exons 4 through 47. Combined with previously reported data, these findings suggest that the incidence of deletions of COL4A5, as opposed to other COL4A5 mutations, is much higher in Alport patients who develop posttransplant anti-GBM nephritis than in the general Alport population. Immunofluorescence studies of kidney from Patient J.E. showed no reactivity of GBM with monoclonal antibodies directed against the alpha 3, alpha 4, and alpha 5 chains of Type IV collagen. This finding confirms that the mutation affecting the alpha 5(IV) chain can interfere with the incorporation of alpha 3(IV) and alpha 4(IV) into the GBM. PMID- 7993996 TI - Mutations in the vasopressin V2 receptor gene in two families with nephrogenic diabetes insipidus. AB - Congenital nephrogenic diabetes insipidus (CNDI) is a rare X-linked disorder in which the renal collecting duct is unresponsive to arginine vasopressin, and thus, the urine is consistently hypotonic to plasma. As a result, affected individuals are unable to concentrate urine and suffer from episodes of severe dehydration and hypernatremia. Recently, the association between arginine vasopressin V2 receptor gene mutations and CNDI has been demonstrated. In this report, two additional novel molecular defects of the arginine vasopressin V2 receptor gene in CNDI families are described. In one family, the affected individual demonstrated a G-->T transversion causing a nonsense mutation in codon 231. This mutation results in a glutamic acid becoming a termination codon, causing premature termination and truncation of the encoded receptor protein. This mutation causes a NciI site within the gene to be abolished and a BsaWI site to be created. In the second family, affected individuals showed a 28-basepair duplicating insertion in the very beginning of exon 2 down-stream of the splice acceptor site. It was hypothesized that an insertion mutagenesis mechanism involves the formation of a stem-loop structure within the newly synthesized DNA strand, followed by a slipped mispairing. This may be a general mechanism for the deletion or insertion of repeated sequences within the genome. Recent data show that G-protein-coupled receptors are susceptible to many different mutations that often result in the loss of function, causing a similar clinical phenotype. PMID- 7993997 TI - Reduced production, absorption, and elimination of erythropoietin in uremia compared with healthy volunteers. AB - The purpose of this study was to investigate the metabolism of erythropoietin (EPO) in uremia compared with healthy subjects. Twenty-one patients (nine men and 12 women) with end-stage renal failure and anemia and 12 healthy volunteers (3 women and nine men) were studied. The pharmacokinetic parameters were calculated after an i.v. and a femoral sc injection of 100 U/kg of recombinant human EPO. The serum EPO (s-EPO) was measured by radio-immunoassay at regular intervals until 48 h (i.v.) and 120 h (sc). In uremia, the median terminal elimination half life was significantly longer (8.31 versus 4.92 h; P < 0.001) and the clearance was reduced (5.00 versus 7.88 mL/min per 1.73 m2; P < 0.01). The volume of distribution was (3.70 versus 3.31 L/1.73 m2) not significant. The estimated endogenous EPO production was significantly lower in uremia (146 versus 290 U/day per 1.73 m2; P < 0.001). After sc administration, the bioavailability was significantly lower in the patients (23.7 versus 38.5%; P < 0.01), and the maximal s-EPO was lower (113 versus 153 U/L; P < 0.05) and delayed (15.4 versus 11.0 h; P < 0.02), but the mean input time (sc) was not significantly different (23.3 versus 27.8 h). The basal s-EPO was lower in the uremic patients (20.0 versus 26.3 U/L; P < 0.05). There was no difference between patients treated with hemodialysis and peritoneal dialysis or between uremic men and women. There was no correlation between the pharmacokinetic parameters and age.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7993998 TI - Uremic serum subfraction inhibits apolipoprotein A-I production by a human hepatoma cell line. AB - Abnormalities in lipoprotein metabolism are common in uremic patients and may represent an additional risk factor for the development of atherosclerosis. Despite the frequent occurrence of lipoprotein abnormalities, the role of various serum toxins and subfractions that accumulate in uremic patients on lipoprotein metabolism is not clearly understood. This study addressed the role of uremic toxins on lipoprotein metabolism by examining the effect of a 500 to 2,000-d subfraction obtained from the serum of uremic and control subjects on the synthesis of apolipoprotein (apo) A-I in a human hepatoma cell line (Hep-G2). Serum subfractions obtained from uremic patients inhibited apo A-I synthesis and secretion by Hep-G2 cells in a dose-dependent manner as measured by (3H)leucine incorporation into apo A-I, immunoprecipitation, and ELISA. The uremic serum subfraction decreased the mRNA expression for apo A-I in Hep-G2 cells when compared with controls. These observations suggest that a component of uremic serum can have the potential to inhibit hepatic apo A-I synthesis and may adversely influence high-density lipoprotein metabolism, thus increasing the risk for the development of atherosclerotic vascular complications in uremic patients. PMID- 7993999 TI - Human renal cortical interstitial cells with some features of smooth muscle cells participate in tubulointerstitial and crescentic glomerular injury. AB - In most forms of renal injury, even those due to a primary glomerular process, the extent of tubulointerstitial scarring is a critical determinant of renal functional reserve and prognosis. Yet, little is known about the functional characteristics of the interstitial cells that mediate the processes of chronic tubulointerstitial injury. In this study, tissues from normal kidney (N = 7), from nephrectomies removed for allograft rejection (N = 14) and chronic pyelonephritis (N = 2), and from a cohort of 128 biopsies exhibiting a range of glomerulopathies and tubulointerstitial injury were characterized with antibodies to mesenchymal cells (alpha-smooth muscle actin, desmin) by immunohistology. Selected normal kidneys were also studied by immunoelectron microscopy. Normal adult kidneys contain a widespread population of cortical interstitial cells that constitutively express alpha-smooth muscle actin but not desmin. Immunoelectron microscopy shows that these cells are fibroblasts and not capillary endothelial cells or leukocytes. It has previously been shown that these cells constitutively express platelet-derived growth factor receptor beta and the p75 nerve growth factor receptor. Accumulations of cells expressing smooth muscle actin were identified at sites of chronic tubulointerstitial injury in allograft and pyelonephritic kidneys. The cohort of 128 renal biopsies also revealed accumulations of muscle actin-expressing cells at sites of interstitial injury. These findings demonstrate that a population of interstitial cells with some muscle-like features can be identified in normal kidneys.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7994000 TI - Acute nitric oxide blockade amplifies the renal vasoconstrictor actions of angiotension II. AB - The tone in the renal vasculature is determined by the balance between vasoconstrictor and vasodilator agents. In this study, the effect on renal function was investigated when the acute blockade of the endogenous nitric oxide system was superimposed on a state of high circulating angiotensin II. Studies were conducted in the conscious, unstressed rat measuring renal function before and during acute systemic nitric oxide blockade with nitro-L-arginine methyl ester and with or without concomitant angiotensin II infusion. Nitric oxide blockade alone, in the presence of normal, unstimulated levels of endogenous angiotensin II, caused a large rise in blood pressure and a doubling of renal vascular resistance. The infusion of angiotensin II alone produced a mild rise in systemic blood pressure and a small (30%) rise in renal vascular resistance. When nitric oxide blockade was combined with angiotensin II infusion, the rise in blood pressure was similar to that produced by nitric oxide blockade alone but the increase in renal vascular resistance was much greater (350%), leading to marked declines in renal function. These studies demonstrate that when angiotensin II levels are acutely elevated and are controlling renal vascular tone, nitric oxide is essential for the maintenance of adequate renal perfusion and function. PMID- 7994001 TI - The origin of urinary angiotensins in humans. AB - To examine whether urinary angiotensin (ANG) I and II excretion responds to changes in plasma ANG I and ANG II, ANG I or ANG II was infused in seven healthy subjects pretreated with a 340-mmol sodium diet and 20 mg of enalapril twice daily. Infusion rates were 4, 8, 16, and 32 pmol/kg per minute for ANG I and 1, 4, and 8 pmol/kg per minute for ANG II. Baseline ANG I and ANG II excretions averaged 10 and 20 fmol/min, respectively, which is approximately 0.3 and 5% of the filtered loads. Despite a 20-fold increase in plasma ANG I during ANG I infusion, urinary ANG I did not increase. Similarly, the 30-fold increase in plasma ANG II during ANG II infusion was not followed by an increase in ANG II excretion, but in fact by a decrease in urinary ANG I and ANG II. In a separate study, urinary ANG I and ANG II were measured before and after the oral administration of 20 mg of enalapril in eight healthy volunteers taking 400, 200, or 20 mmol of NaCl daily. In contrast to the considerable effects on plasma ANG I and ANG II and renal hemodynamics, enalapril had no effect on urinary ANG I and ANG II. Variation of sodium intake had predictable effects on plasma ANG I and ANG II but did not affect urinary ANG I and ANG II. These data suggest that urinary ANG I and ANG II originate from an intrarenal source. The independency of sodium intake and ANG-converting enzyme make the juxtaglomerular apparatus as the site responsible for the production of this ANG unlikely. PMID- 7994002 TI - Renal tubular dysgenesis: evidence of abnormality in the renin-angiotensin system. AB - Renal tubular dysgenesis is an autosomal recessive condition characterized by short, abnormally developed cortical tubules that lack proximal differentiation. Despite the lack of normal proximal tubules, the major site of water resorption in the kidney, the principal clinical manifestations are caused by fetal and neonatal oliguria. The kidneys in three cases of neonatal renal tubular dysgenesis were found to contain large amounts of immunohistochemically reactive renin in preglomerular arterioles, glomerular hilums, and glomerular mesangial areas, far exceeding the intensity of staining and the numbers of sites stained in control kidneys. The increased accumulation of renin may reflect strong local vasoconstriction, which is responsible for reduced glomerular perfusion. This accumulation suggests faulty feedback control of renin secretion, the basis of which is still to be identified. PMID- 7994003 TI - Proinflammatory cytokines and hemofiltration membranes. AB - To determine whether the clinical improvement noted in some septic patients undergoing hemofiltration is in part due to the removal of proinflammatory mediators, in vitro hemofiltration of a 1% albumin solution containing recombinant human tumor necrosis factor alpha and interleukin-1 was performed through a variety of hemofilters. Observed sieving coefficients of these cytokines was much higher (up to 0.35) than expected, considering their molecular weights of 17 kd. In addition, binding of up to 32% of the total mass to selected membranes (polyamide and AN69) was noted. These data are consistent with the concept that either the convective or adsorptive removal of proinflammatory cytokines may play role in the clinical efficacy of hemofiltration in sepsis. PMID- 7994004 TI - Proposal to establish a National Institute of Kidney and Urologic Diseases, a report of the National Kidney and Urologic Diseases Advisory Board. AB - In 1990, the National Kidney and Urologic Diseases Advisory Board published a long-range plan entitled "Window on the 21st Century." In that plan, the Board recommended that Congress establish a new National Institute of Kidney and Urologic Diseases (NIKUD). This recommendation stemmed from the Board's appreciation that patient morbidity and mortality from kidney and urologic diseases continue to increase and that a focused, well-funded research endeavor is the only real hope for reversing this trend. In 1992, the Board established a special subcommittee to further consider the establishment of a National Institute of Kidney and Urologic Diseases. The Subcommittee sought input from a wide variety of extramural and intramural sources. American Urologic Association- A new devoted institute would provide coordination and expansion of basic research into kidney and urologic diseases, now fragmented and underfunded within multiple institutes. The research areas of kidney and urologic diseases are not currently receiving adequate or appropriate attention proportionate to their prevalence and their adverse effect on society. American Society of Nephrology- The ASN supports the establishment of a separate kidney and urology institute. First and foremost, our primary interest is to obtain more support for kidney and urologic diseases. Such research does not receive the emphasis and prominence that it deserves at the National Institutes of Health. ASN believes that a separate institute would provide increased focus for these diseases.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7994005 TI - The presynaptic compartment: signals and targets. AB - Synaptic terminals are key elements in the functional and structural organization of the nervous system. Release of neurotransmitters, i.e. the activity specifically localized at the terminals, not only sustains the transfer of information among adjacent cells, but also contributes significantly to directing the non-random distribution of macromolecules in the plasmalemma of postsynaptic neurons, with major consequences in their general architecture (assembly of postsynaptic densities, dendritic spines, etc.). In order for these specific functions to be carried out, synaptic terminals need to be specialized in a variety of aspects with respect to the rest of the neuron. This minireview is specifically focused on two such aspects, the generation of transduction signals and their mechanism of action on intraterminal targets. In either aspect nerve terminals are by no means fully homogeneous, yet they certainly share a number of common features. These include the predominant role of Ca2+, collaborating however with other second messengers (cAMP, IP3, diacylglycerol) in the control of processes such as transmitter release and its modulation. PMID- 7994007 TI - LTP expression: hanging like a yo-yo? AB - Until a few years ago long-term potentiation or LTP was not a very popular subject for a cell biology-oriented audience. Recently, however, the picture has completely changed, mainly because most of the LTP papers are now dealing with specific molecules, second messengers, biochemical pathways, gene regulation, Ca2+ homeostasis, and so forth. This very big transition, has not led yet to a clear-cut picture on the actual locus of change after LTP induction and on the 'memory' molecule that bears the permanent change. Perhaps the biggest limitation is still the very small knowledge we have on how central synapses work. For this reason, at the moment, the most popular and conservative view is that LTP expression involves both pre- and postsynaptic changes. The aim of this review is to briefly summarize the status of LTP expression and to describe some possible future developments based on new approaches and techniques. PMID- 7994006 TI - Clostridial neurotoxins as tools to investigate the molecular events of neurotransmitter release. AB - The clostridial neurotoxins responsible for tetanus and botulism are eight different proteins, composed of two disulfide-linked polypeptide chains. They bind specifically to the presynaptic membrane via the heavy chain, while the light chain enters the cytosol of the neurons, where it displays a zinc endopeptidase activity directed to proteins of the neuroexocytosis apparatus. Tetanus neurotoxin and botulinum neurotoxin serotypes B, D, F and G cleave specifically and at single different peptide bonds VAMP/synaptobrevin, a component of small synaptic vesicles. In contrast, the other neurotoxins catalyze the hydrolysis of proteins of the presynaptic membrane. Serotypes A and E of botulinum neurotoxin cleave SNAP-25, at different sites located within the carboxyl-terminus, while the specific target of serotype C is syntaxin. PMID- 7994009 TI - Molecular consequences of diffusible signaling: locally distributed synaptic enhancement in hippocampal neurons. AB - The long-lasting increase in synaptic strength known as long-term potentiation is regarded as a potential physiological mechanism for many forms of both developmental and adult neuronal plasticity. In many models of plasticity, intercellular communication has been proposed to account for observations in which simultaneously active neurons are strengthened together. Recent studies indicate that long-term potentiation can be communicated between synapses on neighboring neurons, perhaps via a diffusible messenger. This distributed potentiation provides a potential mechanism for the cooperative strengthening of proximal synapses that underlie common neuronal functions and contribute to a variety of plastic processes in the nervous system. PMID- 7994008 TI - Calcium requirement of long-term depression and rebound potentiation in cerebellar Purkinje neurons. AB - Cerebellar Purkinje neurons (PNs) receive two main excitatory inputs, from climbing fibers and parallel fibers, and inhibitory inputs, from GABAergic interneurons. The synapses formed by parallel fibers and by inhibitory interneurons on PNs are able to undergo long-lasting changes in efficacy. Thus, the excitatory parallel fiber-PN synapse undergoes long-term depression when it is activated in conjunction with climbing fibers. Synaptic inhibition can be potentiated by climbing fiber activity by a mechanism named rebound potentiation, resulting in a more powerful inhibitory effect of GABAergic interneurons. The induction of both long-term depression and rebound potentiation requires a transient elevation of the cytoplasmic calcium concentration ([Ca2+]i). The [Ca2+]i-transient is caused by Ca2+ entry through voltage-gated Ca2+ channels and, possibly, by release of Ca2+ from IP3- and ryanodine-sensitive stores. Direct Ca2+ entry through synaptic AMPA receptor channels seems not to contribute significantly to the Ca2+ signal mediating the induction of both long-term depression and rebound potentiation. PMID- 7994010 TI - The PACAP receptor: generation by alternative splicing of functional diversity among G protein-coupled receptors in nerve cells. AB - Recent molecular characterization of new G protein-coupled receptors (GPCR) draw attention to alternative splicing as a source of structural diversity. After a brief overview of characterized GPCR splice variants, we will describe in more detail the functional properties of the PACAP type I receptor splice variants. Some of these variants are positively coupled to both adenylate cyclase (AC) and phospholipase C (PLC) whereas others do not elicit any stimulation of the PLC or display a qualitatively intermediate phenotype. The PACAP type I receptor is therefore one of the few examples in which alternative splicing is clearly linked to functional diversity. PMID- 7994011 TI - Structure and function of IP3 receptors. AB - The molecular, structural and functional characteristics of the intracellular Ca2+ release channel activated by inositol 1,4,5-trisphosphate (IP3), also named IP3 receptor (IP3R), are described here. We also discuss the differences in primary structure, expression and modulation of the receptor subtypes and their physiological roles. The similarity and differences between the IP3R and the other intracellular Ca2+ channel, the ryanodine receptor, are briefly presented. PMID- 7994012 TI - A stream of broken promises. PMID- 7994013 TI - New instrumentation and technique for obtaining consistent interproximal contacts of direct Class II composite restorations. AB - The difficulty in obtaining tight proximal contacts and properly placed contours in direct Class II composite resin restorations continues to demand a high level of proficiency when using conventional Class II techniques. Despite the highly improved composite resins and fourth-generation dentin bonding systems available, comparatively little advancement has taken place in instrumentation for reducing technique sensitivity and procedural time. This article introduces a prototype instrument which uses simple mechanical principles to overcome the difficulties in placing direct Class II composite restorations. The learning objective of this article is to familiarize the reader with the instrument, its principles, and the application technique. PMID- 7994014 TI - Intra-radicular rehabilitation: a clinical approach. AB - The emphasis in placing posts is shifting from their ability to strengthen the tooth structure to their capacity to provide additional retention and resistance to the displacement of the core material, without inducing undue installation or functional stresses. Numerous post systems are available. The learning objective of this article is to present a recently-introduced system of light-transmitting posts (LTP), with integrated size reamers and metal posts, which simplify the placement technique. A case report is used to illustrate the clinical procedure. PMID- 7994015 TI - Achieving interdental integrity in resin-bonded posterior ceramic restorations. AB - Increased physical strength of ceramic materials and increased bond strength now make it feasible to use these materials in the posterior area, and these restorations are aesthetic to the point of being virtually indistinguishable from natural teeth. These restorations are more technique-sensitive, and the restrictive anatomical proximities present an additional challenge, requiring meticulous attention to preparation, impression, temporization, fabrication, and cementation procedures. The health of the tissues investing and supporting the teeth has long been accepted as essential. The learning objective of this article is to share the knowledge gained in clinical experience with other clinicians. PMID- 7994016 TI - Are all those crowns really necessary? PMID- 7994017 TI - The connective tissue graft with labial vestibular extension. AB - Because of its predictability and simplicity, the connective tissue graft has become the method of choice in most root coverage procedures. However, in cases with prominent frenum involvement and limited vestibular depth, this procedure can be difficult, if not impossible, to accomplish. Building upon a modification of the labial vestibular extension, described by Kazanjian in 1935, a technique is presented, whereby vestibular extension is accomplished in the same one-stage surgical procedure with a connective tissue graft. The learning objective of this article is to introduce this modification of the surgical technique to a larger segment of the clinical profession. PMID- 7994018 TI - What defines a pluripotent hematopoietic stem cell (PHSC): will the real PHSC please stand up! PMID- 7994019 TI - Fanconi anemia and novel strategies for therapy. PMID- 7994020 TI - Interleukin-12: a cytokine produced by antigen-presenting cells with immunoregulatory functions in the generation of T-helper cells type 1 and cytotoxic lymphocytes. PMID- 7994022 TI - Candidate tumor-suppressor genes MTS1 (p16INK4A) and MTS2 (p15INK4B) display frequent homozygous deletions in primary cells from T- but not from B-cell lineage acute lymphoblastic leukemias. AB - Using a Southern blot approach, deletions of MTS1 (multiple tumor-suppressor gene 1) and MTS2 (multiple tumor-suppressor gene 2) candidate tumor-suppressor genes have been studied in primary neoplastic cells from 55 acute lymphoblastic leukemia (ALL) patients. Homozygous MTS1 deletions were found in 20 of 24 T-ALL cases and in only 2 of 31 B-lineage cases (P < .001). The deletions involved MTS1 and MTS2 in most cases. Homozygous MTS2 deletions were observed in 16 of 24 T-ALL cases and in 1 of 31 B-lineage ALLs (P < .001), all of them displaying homozygous MTS1 deletions. In 5 cases (4 T and 1 B), deletions involved MTS1 but spared the MTS2 gene, showing that one deletion breakpoint was located between the two genes within a 25-kb region. In 1 T-ALL case, an MTS1 gene rearrangement has occurred downstream to exon 2. Possible hemizygous deletions were found in 6 cases, 4 of them of the B-cell lineage. In 7 ALL cases, cells obtained at presentation and at first relapse were studied and identical results were observed in 6 cases. In 1 B lineage case, a germline pattern was found at presentation and a possible monoallelic MTS1/MTS2 deletion was observed at relapse. The high frequency of MTS1 and MTS2 homozygous deletions in T-ALLs supports the view that inactivation of these genes plays an important role in the pathogenesis of this type of human leukemia. PMID- 7994021 TI - Organization of the gene for human platelet/endothelial cell adhesion molecule-1 shows alternatively spliced isoforms and a functionally complex cytoplasmic domain. AB - Platelet endothelial cell adhesion molecule-1 (PECAM-1) is a cell-cell adhesion molecule that is expressed on circulating platelets, on leukocytes, and at the intercellular junctions of vascular endothelial cells and mediates the interactions of these cells during the process of transendothelial cell migration. The cDNA for PECAM-1 encodes an open reading frame of 738 amino acids (aa) that is organized into a 27-aa signal peptide, a 574-aa extracellular domain composed of 6 Ig homology units, and a relatively long cytoplasmic tail of 118 aa containing multiple sites for posttranslational modification and postreceptor signal transduction. To provide a molecular basis for the precise evaluation of the structure and function of this transmembrane glycoprotein, we have determined the organization of the human PECAM-1 gene. The PECAM-1 gene, which has been localized to human chromosome 17, is a single-copy gene of approximately 65 kb in length and is broken into 16 exons by introns ranging in size from 86 to greater than 12,000 bp in length. Typical of other members of the Ig superfamily, each of the extracellular Ig homology domains is encoded by a separate exon, consistent with PECAM-1 having arisen by gene duplication and exon shuffling of ancestral Ig superfamily genes. However, the cytoplasmic domain was found to be surprisingly complex, being encoded by seven short exons that may represent discrete functional entities. Alternative splicing of the cytoplasmic tail appears to generate multiple PECAM-1 isoforms that may regulate phosphorylation, cytoskeletal association, and affinity modulation of the mature protein. Finally, a processed pseudogene having 76% identity with PECAM-1 cDNA was identified and localized to human chromosome 3. These findings should have important implications for structure/function analysis of PECAM-1 and its role in vascular adhesive interactions. PMID- 7994023 TI - Identification of potential hot spots in the carboxy-terminal part of the Epstein Barr virus (EBV) BNLF-1 gene in both malignant and benign EBV-associated diseases: high frequency of a 30-bp deletion in Malaysian and Danish peripheral T cell lymphomas. AB - In this study, we have sequenced the C-terminal part of the Epstein-Barr virus (EBV)-BNLF-1 gene encoding for the latent membrane protein-1 from tissues of EBV positive Danish Hodgkin's disease (HD) and of Danish and Malaysian peripheral T cell lymphomas (PTLs) and from tonsils of Danish infectious mononucleosis (IM). Our study showed that some of the 7 single-base mutations and the 30-bp deletion previously detected between codons of amino acid 322 and 366 in the BNLF-1 gene of the nasopharyngeal carcinoma cell line CAO were present in all Malaysian PTLs and in 60% of the Danish PTLs. In HD and the IM cases, the mutations were present in about 30%. The 30-bp deletion and the single base mutations occurred independently, and mutations were detectable in the majority of EBV type B positive cases. These findings suggest that the 30-bp deletion and the 7 single base mutations in the C-terminal part of the CAO-BNLF-1 gene do not characterize a new EBV type A substrain. Rather, some of the positions of single base mutations and the 30-bp deletion are hot spots that may have mutated independently through the evolution of EBV strains. PMID- 7994024 TI - Long-term follow-up of patients with hairy cell leukemia after treatment with 2' deoxycoformycin. AB - Twenty-four patients with advanced hairy cell leukemia treated with 2' deoxycoformycin (dCF) were studied after achieving complete remission to determine the impact of treatment on survival, disease-free survival, long-term complications of treatment, and response to retreatment. At a median follow-up time of 82 months (range, 54 to 104 months), 23 of 24 patients remain alive. One patient has died of recurrent disease refractory to treatment. Of the remaining 23 patients, 11 have relapsed at a median time of 30 months (range, 7 to 80 months) after treatment completion. Of these 11 patients, 7 have been retreated with dCF or 2'-chlorodeoxyadenosine (2-CdA), including one patient that was retreated twice. All seven patients have responded, with five patients achieving second complete remission. Two patients have had normalization of blood cell counts, but repeat bone marrows have not been performed. No serious infections have been seen in dCF-treated patients during follow-up. One case of Hodgkin's disease and three cases of skin malignancies have developed in these 24 patients. From initiation of treatment, survival is 93 months (range, 63 to 116 months). We concluded that dCF significantly prolongs the survival of patients with advanced hairy cell leukemia without resultant long-term complications. It is too early to predict if this therapy will be curative for the patients still in remission. PMID- 7994026 TI - Induction of anti-recombinant human granulocyte-macrophage colony-stimulating factor (Escherichia coli-derived) antibodies and clinical effects in nonimmunocompromised patients. AB - The pharmacokinetics of recombinant human granulocyte-macrophage colony stimulating factor (rhGM-CSF), induction of anti-GM-CSF antibodies, and clinical effects related to the induction of the antibodies were analyzed in patients with metastatic colorectal carcinoma (CRC) who were not on chemotherapy (n = 20, nonimmunocompromised patients). rhGM-CSF (250 micrograms/m2/d; Escherichia coli derived) was administered subcutaneously for 10 days every month for 4 months. Eight patients with multiple myeloma (MM) on intensive chemotherapy followed by rhGM-CSF treatment were also included (immunocompromised patients). After a single injection of GM-CSF at the first cycle in CRC patients, the maximum calculated concentration (Cmax) was 5.24 +/- 0.56 ng/mL; the half life (T1/2) was 2.91 +/- 0.8 hours; and the area under the concentration curve (AUC) was 30.86 +/ 6.03 hours x ng/mL (mean +/- SE). No anti-GM-CSF antibodies were detected. During the subsequent cycles, 95% of the CRC patients developed anti-GM-CSF IgG antibodies, which significantly altered the pharmacokinetics of rhGM-CSF at the third and fourth cycles with decreased Cmax (2.87 +/- 0.57 ng/mL; P < .05), T1/2 (1.57 +/- 0.2 hours; P < .05), and AUC (14.90 +/- 4.10 hours x ng/mL; P < .005). The presence of anti-GM-CSF antibodies significantly reduced the GM-CSF-induced enhancement of granulocytes, and there was a clear tendency for a decreased increment of monocytes. Antibodies diminished systemic side effects of rhGM-CSF. Only 1 of 8 MM patients showed a very low anti-GM-CSF antibody titer after GM-CSF therapy, as shown by enzyme-linked immunosorbent assay and Western blot. Therefore, in nonimmunocompromised patients, exogenous nonglycosylated GM-CSF induced an anti-GM-CSF IgG antibody response in practically all patients, which seemed to be of clinical significance. In immunocompromised patients, virtually no significant antibody response was shown. PMID- 7994025 TI - Randomized comparison of interferon-alpha with busulfan and hydroxyurea in chronic myelogenous leukemia. The German CML Study Group. AB - As curative bone marrow transplantation is available only to a minority of patients with chronic myelogenous leukemia (CML), drug therapy remains of central interest. Several nonrandomized studies have suggested that interferon-alpha (IFN) may prolong survival in CML. In a randomized multicenter study the influence of IFN versus busulfan or hydroxyurea (HU) on survival of Philadelphia positive (Ph+) CML was examined. A total of 513 Ph+ patients were randomized for treatment as follows: 133 for IFN, 186 for busulfan, and 194 for HU. IFN-treated CML patients have a significant survival advantage over busulfan-treated (P = .008), but not over HU-treated patients (P = .44). The longer survival is due to slower progression to blast crisis. Median survival of IFN-treated patients is 5.5 years [5-year survival, 59%; 95% confidence interval (CI), 48%-70%], of busulfan-treated patients, 3.8 years (5-year survival, 32%; CI, 24%-40%), and of HU-treated patients, 4.7 years (5-year survival, 44%; CI, 36%-53%). Patients who continue on IFN survive longer than those in whom IFN is discontinued before blast crisis (P = .007). Complete hematologic IFN-responders have a survival advantage over partial responders or nonresponders (P = .02). Cytogenetic IFN responders have no significant survival advantage over nonresponders (P = .2). Patients who attain white blood cell (WBC) counts of 10 x 10(9)/L or less have a survival advantage in the IFN (P = .007) and HU (P = .05) groups. Whereas toxicity in the IFN group was considerably higher than in the busulfan or HU groups, long-lasting cytopenias necessitating discontinuation of therapy as observed with busulfan have not been seen with IFN or HU. The problems of conventional prognostic scores (Sokal's score, Score 1) that we observed in IFN treated patients support the idea that IFN changes the natural course of CML. We conclude that, with regard to survival of CML in the chronic phase, IFN is superior to busulfan and as effective as HU. Whether and to what extent IFN is superior to HU appears to depend, at least in part, on the degree of WBC suppression by HU-therapy and on the risk profile of the patients. PMID- 7994027 TI - Changes in G protein pattern and in G protein-dependent signaling during erythropoietin- and dimethylsulfoxide-induced differentiation of murine erythroleukemia cells. AB - We have studied the expression of G protein subtypes and the role of G protein dependent signaling in two subclones of RED-1 cells, an erythropoetin(Epo) sensitive, murine erythroleukemia cell line. Clone 6C8 showed terminal erythroid differentiation in response to a combined treatment with Epo and dimethylsulfoxide. Clone G3 was resistant to these inducers, but responded to Epo with enhanced proliferation. We measured G protein alpha subunit levels by toxin catalyzed adenosine diphosphate (ADP)-ribosylation with [32P]-nicotinamide adenine dinucleotide (NAD) and by semiquantitative immunoblotting with specific antisera. Native RED-1 cells expressed G alpha i2, alpha i3, alpha s, and alpha q/11, but not alpha i1 and alpha o. Terminal differentiation was associated with a selective loss (approximately 80%) of G alpha i3 and an increase in a truncated cytosolic form of G alpha i2, while the membrane levels of alpha i2, alpha q/11, and alpha s did not change significantly. Treatment of G3 cells with the inducers was without effect on G protein abundance. However, except for alpha s, G3 cells contained significantly higher levels of the different G protein alpha subunits tested. Stimulation of G protein-coupled receptors by thrombin and ADP caused a pertussis toxin (PTX)-inhibitable transient increase in intracellular Ca2+ that was markedly reduced in differentiated cells. In G3 cells, but not in 6C8 cells, thrombin also caused a PTX-sensitive inhibition of isoprenaline-stimulated cyclic 3',5'-adenosine monophosphate (cAMP) formation. Our results show that specific alterations in G protein expression and function are associated with erythroid differentiation of erythroleukemia cells but do not prove a causal relationship. The loss of G alpha i3 may affect cellular responses that are mediated via P2T purine or thrombin receptors. PMID- 7994028 TI - Retinoids (all-trans and 9-cis retinoic acid) stimulate production of macrophage colony-stimulating factor and granulocyte-macrophage colony-stimulating factor by human bone marrow stromal cells. AB - Retinoic acids (RAs) exert pleiotropic effects on cellular growth and differentiation. All-trans retinoic acid (ATRA) and 9-cis retinoic acid (9-cis RA), a stereoisomer of ATRA, induce differentiation of leukemic cell lines and cells from patients with acute myelogenous leukemia (AML) in vitro. Despite information on the effects of RAs on hematopoietic cells, little is known about how RAs act on the hematopoietic microenvironment, especially on bone marrow stromal cells. Based on recent observations that various cytokines produced mainly by bone marrow stromal cells regulate hematopoiesis, we analyzed the effects of RAs on cytokine production by these cells. ATRA or 9-cis RA treatment of human bone marrow stromal cell line KM101, which produces macrophage colony stimulating factor (M-CSF) and granulocyte-macrophage colony-stimulating factor (GM-CSF) constitutively, enhanced mRNA levels of both cytokines in a dose dependent manner. Both RAs also stimulated M-CSF production from primary cultures of human bone marrow stromal cells. Both retinoic acid receptor (RAR)-alpha and retinoid X receptor (RXR)-alpha were expressed constitutively in KM101 cells. ATRA did not affect the expression of either receptor, whereas 9-cis RA increased RXR-alpha mRNA expression in a dose-dependent manner, but did not affect levels of RAR-alpha mRNA. These findings may have important biologic implications for both the role of RAs in hematopoiesis and the therapeutic effects of ATRA on the hematopoietic microenvironment in patients with acute promyelocytic leukemia (APL). PMID- 7994029 TI - Regulation of cytokine expression by interferon-alpha in human bone marrow stromal cells: inhibition of hematopoietic growth factors and induction of interleukin-1 receptor antagonist. AB - We investigated the effects of interferon-alpha (IFN-alpha) on the expression of cytokines by human bone marrow stromal cells. Production of granulocyte macrophage colony-stimulating factor (GM-CSF), granulocyte-CSF (G-CSF), and interleukin-1 beta (IL-1 beta) in stromal cell layers was induced by incubation with IL-1 alpha, tumor necrosis factor (TNF), or lipopolysaccharide (LPS). Addition of IFN-alpha to such stimulated cultures resulted in a strong downregulation of mRNA expression of GM-CSF and IL-1 beta. Similarly, the protein levels of GM-CSF and IL-1 beta were significantly reduced by IFN-alpha, whereas G CSF production was only moderately inhibited. In contrast, IFN-alpha markedly stimulated the production of IL-1 receptor antagonist (IL-1RA) by stromal cells. The inhibition of cytokine expression resulted in a reduced hematopoietic activity of stromal cells, indicated by a reduced proliferation of the factor dependent cell line MO7e on IFN-alpha-treated stromal cells. In the presence of cycloheximide (CHX), IFN-alpha failed to inhibit IL-1 mRNA expression, whereas the regulation of GM-CSF and IL-1RA by IFN-alpha was not affected. Our results indicate that the myelosuppressive effects of IFN-alpha, as observed in therapeutic applications or associated with viral infections, are, in part, indirectly mediated by inhibition of the paracrine production of hematopoietic growth factors. PMID- 7994030 TI - The STRO-1+ fraction of adult human bone marrow contains the osteogenic precursors. AB - The monoclonal antibody STRO-1 identifies clonogenic bone marrow stromal cell progenitors (fibroblast colony-forming units [CFU-F]) in adult human bone marrow. These STRO-1+ CFU-F have previously been shown to give rise to cells with the phenotype of fibroblasts, adipocytes, and smooth muscle cells. In this study, the osteogenic potential of CFU-F derived from the STRO-1+ fraction of adult human bone marrow was determined. CFU-F were isolated from normal bone marrow aspirates by fluorescence activated cell sorting, based on their expression of the STRO-1 antigen. Osteogenic differentiation was assessed by the induction of alkaline phosphatase expression, by the formation of a mineralized matrix (hydroxyapatite), and by the production of the bone-specific protein osteocalcin. STRO-1+ cells were cultured in the presence of dexamethasone (DEX; 10(-8) mol/L), ascorbic acid 2-phosphate (ASC-2P; 100 mumol/L), and inorganic phosphate (PO4i; 2.9 mmol/L). After 2 weeks of culture, greater than 90% of the cells in each CFU F colony stained positive for alkaline phosphatase using a monoclonal antibody specific for bone and liver alkaline phosphatase. Alkaline phosphatase activity was confirmed by histochemistry. A mineralized matrix developed in the CFU-F cultures, after 4 weeks of culture in the presence of DEX, ASC-2P, and PO4i. Mineralization was confirmed by both light and electron microscopy. The mineral was identified as hydroxyapatite by electron dispersive x-ray microanalysis and by x-ray diffraction analysis. In replicate cultures, osteocalcin release was shown after exposure of the cells to 1,25-dihydroxyvitamin D3 (10(-7) mol/L) both by radioimmunoassay and Northern blot analysis. This work provides direct evidence that adult human bone marrow-derived CFU-F are capable of differentiating into functional osteoblasts and that osteoprogenitors are present in the STRO-1+ population. PMID- 7994032 TI - Molecular cloning, characterization, and chromosomal localization of a novel protein-tyrosine phosphatase, HPTP eta. AB - Protein-tyrosine phosphatases (PTPases) are considered to play an important role in signal transduction. We previously identified partial sequences of three novel PTPases in a human leukemic cell line. F-36P. We describe here cloning, characterization, and chromosomal localization of one of the newly identified PTPases, termed as HPTP eta (human protein-tyrosine phosphatase eta). The deduced amino acid sequence was composed of an extracellular region homologous to fibronectin type III repeats, a transmembrane region, and a cytoplasmic region containing a single PTPase-like domain. Based on its primary structure, this clone belongs to type-III receptor-type PTPases. The PTPase-like domain showed PTPase activity when expressed in Escherichia coli. Antibody against the extracellular region detected a protein of 220 to 250 kD in human hematopoietic cell lines expressing HPTP eta mRNA. The antibody also recognized a protein of approximately the same molecular weight in COS cells transfected with HPTP eta cDNA, indicating that the antibody specifically recognized HPTP eta gene product and that the cloned cDNA contained full-length coding region. The chromosomal localization determined by fluorescence in situ hybridization showed that the HPTP eta gene was located at chromosome 11p11.2 on the short arm of chromosome 11, which is frequently lost or deleted in human carcinomas. PMID- 7994031 TI - Expression and function of the human granulocyte-macrophage colony-stimulating factor receptor alpha subunit. AB - To determine the expression and function of the granulocyte-macrophage colony stimulating factor (GM-CSF) receptor alpha chain (GMR alpha) during hematopoiesis and on leukemic cells, monoclonal antibodies were raised by immunizing mice with cells expressing high levels of human GMR alpha. A pool of five antibodies isolated from three different mice was used to characterize GMR alpha. This antibody pool (anti-GMR alpha) immunoprecipitated a protein with the expected molecular weight of GMR alpha from COS cells transiently transfected with the GMR alpha gene. In factor-dependent cells, GMR alpha existed as a phosphoprotein. However, its phosphorylation was not stimulated by the presence of GM-CSF. Anti GMR alpha inhibited the GM-CSF-dependent growth of cell lines and normal bone marrow cells and inhibited the binding of iodinated GM-CSF to its receptor. Cell surface expression of GMR alpha was examined using anti-GMR alpha and flow cytometry. GMR alpha was readily detectable on both blood monocytes and neutrophils. In adherence-depleted normal bone marrow, two separate populations expressed GMR alpha. The most positive cells were predominantly macrophages, whereas the cells that expressed less GMR alpha were largely myelocytes and metamyelocytes. A small population of lin-CD34+ or CD34+CD38- cells also expressed GMR alpha, but they were not capable of significant growth in colony forming assays. In contrast, the majority of lin-CD34+ and CD34+CD38- cells were GMR alpha-, yet they produced large numbers of myeloid and erythroid colonies in the same assay. Malignant cells from patients with leukemia were also tested for GMR alpha expression. All of the myeloid leukemias and only rare lymphoid leukemias surveyed tested positive for GMR alpha. These results show that anti GMR alpha is useful for the functional characterization of the GMR alpha and for the detection of myeloid leukemia and that GMR alpha is expressed on certain lineages throughout hematopoietic development; however, progenitors that express the receptor may have a reduced capacity to proliferate in response to hematopoietic growth factors. PMID- 7994033 TI - Identification of a novel thrombin receptor sequence required for activation dependent responses. AB - Thrombin receptor (TR) activation by alpha-thrombin requires proteolytic cleavage, although synthetic peptides modeled after the new N-terminus directly effect receptor activation without cleavage, presumably by interacting with an unidentified region of the receptor. To further define critical residues responsible for receptor activation, we performed epitope mapping of anti-TR1 160, a previously described polyclonal antibody that inhibits peptide ligand induced receptor activation in various cell types expressing a functional TR. An enzyme-linked immunosorbent assay (ELISA) using overlapping decapeptides derived from the TR extracellular domains identified four immunodominant peaks within the long N-terminal extension centered between amino acids 34-44, 48-67, 65-79, and 87-94. Soluble peptides derived from regions 83-94, but not those from other regions of the receptor, neutralized the ability of anti-TR1-160 to inhibit peptide ligand-induced platelet aggregation, suggesting that antibodies directed against this region of the TR are important in ligand-mediated activation. Thrombin receptor mutants lacking discrete regions of the TR were subsequently evaluated using microinjected Xenopus oocytes. Whereas a TR mutant lacking amino acid residues Thr67-Lys82 (TR delta 67-82) showed normal to exaggerated responses to either alpha-thrombin or synthetic peptide ligands, only TR mutants with limited deletions spanning the residues Gln83-Ser93 exhibited dysfunctional responses to either agonist (200 nmol/L alpha-thrombin or 200 mumol/L TR42-47). These data provide a model for receptor activation that implicates a discrete and previously uncharacterized sequence within the TR N-terminal extension that is necessary for initiation of signal transduction events independent of the initiating agonist. PMID- 7994034 TI - Prevalence and clinical significance of elevated antiphospholipid antibodies in patients with idiopathic thrombocytopenic purpura. AB - Antibodies against phospholipid antigens (APA) have been demonstrated in idiopathic thrombocytopenic purpura (ITP), but their clinical and pathogenetic significance has remained elusive. In this study we analyzed the prevalence and clinical features of ITP patients with elevated APA. In addition, we prospectively evaluated APA levels after treatment with corticosteroids and compared them with platelet-associated immunoglobulin (PAIgG) titers. We studied 149 patients with newly diagnosed ITP. Of these, 78 had a platelet count less than 50 x 10(9)/L and received an initial treatment with oral prednisone (PDN). In 71 asymptomatic cases with platelet counts between 50 x 10(9)/L and 120 x 10(9)/L, no therapy was scheduled. However, in five of them, the platelet count fell below 50 x 10(9)/L after more than 12 months; these patients were treated with PDN. Tests for APA included the measurement of anticardiolipin antibodies (ACA) with a solid-phase immunoassay and the detection of the lupus-like anticoagulant (LA) activity with coagulation tests that included kaolin-clotting time, dilute Russel's Viper venom time, activated partial thromboplastin time (aPTT), and dilute aPTT. Controls consisted of 174 apparently healthy subjects. Either LA or elevated ACA was seen in 69 patients (46.3%) at diagnosis. LA and ACA were both elevated in 24 cases (16.1% of the overall patient population and 34.8% of patients with high APA concentrations). No correlation was found between LA ratio values and ACA-IgG or -IgM titers, or between ACA-IgG and ACA-IgM levels. The presence of these antibodies was not associated with sex, age, platelet count, or the severity of hemorrhages. PAIgG was detected in 106 of 127 cases (83%). Again, no relationship was observed with clinical parameters or with APA levels. However, all cases with elevated APA also had increased PAIgG. With regard to the clinical course, we were not able to detect any significant difference between patients with normal and elevated APA. An initial complete response to prednisone treatment was observed in 43 of 83 cases (51.8%), with 13 (15.7%) achieving a prolonged complete remission. APA levels were not significantly modified after PDN therapy and on relapse. We conclude that APA positivity is a common finding in patients with ITP and does not select a category with different clinical features. APA levels are not influenced by immunosuppressive therapy with steroids and are not related to the activity of the disease. Therefore, we do not support a role for APA in the pathogenesis of ITP. PMID- 7994035 TI - Hereditary antithrombin deficiency: heterogeneity of the molecular basis and mortality in Dutch families. AB - We studied the molecular basis and genetic heterogeneity of hereditary antithrombin (III) deficiency in nine Dutch families. Polymerase chain reaction (PCR) amplification and direct sequencing of all antithrombin gene exons and flanking intronic regions identified mutations in eight families. Given the opportunity to correlate the molecular basis with survival, we addressed the relevance of molecular defects to mortality in inherited antithrombin deficiency. The defects included single nucleotide deletions (7671 del G, 7768-69 del G) and insertions (5501 ins A, 2463 G-->TC) that lead to frameshifts, a single base substitution [5381 C-->T (129Arg-->stop)] leading to a premature termination codon, and single base substitutions resulting in amino acid substitutions [2652 A-->C (63Tyr-->Ser), 13380 T-->C (421Ile-->Thr), and 13407 G-->T (430Cys-->Phe)]. All affected individuals were heterozygous for the defects. Previously we found in Dutch families that antithrombin deficiency did not lead to higher mortality compared with the general population. In accordance with these findings, we observed no excess mortality in the nine families [Observed:Expected, 52:52.6; standardised mortality ratio (SMR) 1.0, 95% confidence interval (CI), 0.7-1.3]. Our findings confirmed a considerable genetic heterogeneity underlying antithrombin deficiency. We therefore concluded that the lack of excess mortality in these families is not caused by a Dutch mild defect. We suggest that the longevity is not affected by molecular defects in the antithrombin gene and hypothesize that differences in mortality or natural history between families most likely result from other (genetic) risk factors. PMID- 7994036 TI - Role of the B domain for factor VIII and factor V expression and function. AB - Factor V and factor VIII are homologous cofactors in the blood coagulation cascade that have the domain structure A1-A2-B-A3-C1-C2, of which the B domain has extensively diverged. In transfected COS-1 monkey cells, expression of factor VIII is approximately 10-fold less efficient than that of factor V, primarily because of inefficient protein secretion and, to a lesser extent, reduced mRNA expression. To study the functional significance and effect of the B domain on expression and activity, chimeric cDNAs were constructed in which the B domains of factor V and factor VIII were exchanged. Expression of a factor VIII chimera harboring the B-domain of factor V yielded a fully functional factor VIII molecule that was expressed twofold more efficiently than wild-type factor VIII because of increased mRNA expression. Thus, sequences within the factor VIII B domain were not responsible for the inefficient secretion of factor VIII compared with factor V. Expression of a factor V chimera harboring the B domain of factor VIII was slightly reduced compared with wild-type factor V, although the secreted molecule had significantly reduced procoagulant activity correlating with dissociated heavy and light chains and resistance to thrombin activation. Interestingly, the factor V chimera containing the factor VIII B domain was efficiently activated by Russell's viper venum (RVV). A factor V B domain deletion (residues 710-1545) molecule also exhibited significantly reduced procoagulant activity caused by resistance to thrombin cleavage and activation, although this molecule was activatable by RVV. These results show that, in contrast to factor VIII, thrombin activation of factor V requires sequences within the B domain. In addition, thrombin activation of factor V occurs through a different mechanism than activation by RVV. PMID- 7994037 TI - A defect in the early phase of T-cell receptor-mediated T-cell activation in patients with common variable immunodeficiency. AB - Common variable immunodeficiency (CVID) is characterized by an impairment of specific antibody production and a decrease in all or selected Ig isotypes. Abnormalities at the level of the B cells, T cells, and antigen-presenting cells have been described. In the present study, we have focused our attention on T cell activation in CVID. T cells from 15 of 24 patients failed to respond to recall antigens (eg, tetanus toxoid, Escherichia coli). Of these 15 patients, 11 were studied in detail and showed significantly decreased T-cell proliferative responses and/or decreased interleukin-2 and interferon-gamma production on T cell receptor-mediated stimulation with recall antigens and superantigens (staphylococcal enterotoxins [SE]); however, T-cell response to mitogens (anti CD3 monoclonal antibody, phytohemagglutinin) was normal. The defect in interleukin-2 and interferon-gamma release on tetanus toxoid stimulation could also be documented in purified CD4 T cells of the patients and was present in patients with high and normal CD8 counts alike. Furthermore, patients' T cells failed to mount a significant elevation in free intracellular calcium (Ca++ flux) in response to superantigen, whereas the response to phorbol myristate acetate and ionomycin, bypassing receptor-mediated signaling, was unimpaired. These results indicate a defect in the early phase of T-cell activation after triggering of the T-cell receptor in a significant subgroup of CVID patients. PMID- 7994038 TI - Interleukin-1 induces interleukin-8 secretion from endothelial cells by a juxtacrine mechanism. AB - Inflammation is characterized by migration of neutrophils through the endothelium, and the chemokine interleukin-8 (IL-8) appears to be involved. We asked whether adherence of cells bearing a membrane-form of interleukin 1 (IL-1) induces IL-8 secretion from human umbilical vein endothelial cells (HUVEC) and fibroblasts. Human peripheral blood mononuclear cells (PBMC) were stimulated with endotoxin for 12 hours and then fixed for 4 hours with paraformaldehyde. When these cells were added to HUVEC or fibroblasts, IL-8 production was induced. This stimulation by fixed PBMC was attributed to IL-1, because pretreatment of HUVEC or fibroblasts with IL-1 receptor antagonist (IL-1Ra) reduced the induction by 95% and 80%, respectively, P < .005. Using anti-IL-1 alpha monoclonal antibodies, reduction was complete, whereas anti-IL-1 beta had no effect. IL-1 alpha was shown on the surface of monocytes by fluorescence-activated cell sorter (FACS) analysis. Blockade of IL-1 receptors on PBMC did not affect the activity of membrane-associated IL-1 alpha, indicating that IL-1 is not anchored to the membrane through its receptors. However, PBMC treated with D-mannose before fixation resulted in a loss of activity; this loss of activity was associated with release of IL-1 alpha, not IL-1 beta, into the supernatant. Thus, anchoring of IL-1 alpha to the membrane may be via a lectin or mannose receptor-like interaction. Blockade of membrane IL-1 alpha required a 30-fold and fivefold excess of IL-1Ra compared with the amount required to block soluble IL-1 beta and IL-1 alpha, respectively. We conclude that the fixed PBMC IL-8 inducing activity is almost entirely caused by IL-1, that this represents IL-1 alpha bound to a surface lectin or mannose receptor on the monocyte, and that it functions in inflammation via juxtacrine interactions. PMID- 7994039 TI - Expression and regulation of tumor necrosis factor, interleukin-2, and hematopoietic growth factor receptors in B-cell chronic lymphocytic leukemia. AB - Leukemic cells from patients with B-cell chronic lymphocytic leukemia (B-CLL) express tumor necrosis factor (TNF) and interleukin-2 (IL-2) receptors, but only a low proliferative response can be elicited in vitro by TNF alpha and IL-2. To investigate the functional properties of IL-2 and TNF alpha on leukemic B cells, we evaluated (1) the regulation of expression of TNF receptors (TNF-R) and IL-2 receptors on leukemic B cells after culture with TNF alpha and IL-2; (2) the effect of the combination of TNF alpha and IL-2 in a proliferative in vitro assay; and (3) the expression and regulation by these cytokines of receptors for hematopoietic factors, including IL-3, granulocyte colony-stimulating factor (G CSF), and granulocyte-macrophage colony-stimulating factor (GM-CSF). Flow cytometry analysis showed that freshly isolated leukemic cells from B-CLL patients bear the 75-kD TNF-R and the 55-kD IL-2R; TNF alpha was able to upregulate the 55-kD IL-2R but not the 75-kD TNF-R. On the other hand, IL-2 was not able to modify the expression of the above-mentioned receptors. Although each cytokine alone was unable to induce a relevant proliferation of leukemic cells, a synergistic proliferative effect was detected when these cytokines were used in combination. Leukemic B cells from B-CLL patients bear receptors for hematopoietic factors (IL-3, G-CSF, and GM-CSF) that were upregulated in vitro by IL-2 via the 55-kD IL-2R. On the contrary, TNF alpha was unable to affect the expression of the above-mentioned receptors. These results indicate (1) that IL-2 and TNF receptors are related to each other on leukemic cells in B-CLL and (2) that the IL-2R is involved in the regulation of other structures, ie, CSF receptors, thus pointing to another functional role of this receptor complex and the related cytokine in leukemic cells. PMID- 7994041 TI - Changes in cytokine secretion patterns of CD4+ T-cell clones in human immunodeficiency virus infection. AB - In addition to the loss of CD4+ T cells in later stages of human immunodeficiency virus (HIV) infection, functional defects of Th cells can already be observed in early infection. Decreased interleukin (IL)-2 and interferon (IFN)-gamma production by CD4+ T cells and diminished delayed type hypersensitivity reactions are indicative for impaired Th1 responses. We studied the cytokine secretion patterns of T-cell clones (TCC) generated by mitogenic stimulation of CD4+ memory T cells. Compared with TCC from HIV-negative controls, TCC isolated from HIV infected individuals consistently showed increased IL-4 production, often paralleled by increased IL-5 and decreased IFN-gamma production. This resulted in a decreased percentage of Th1 clones with an increase in Th0 clones. To rule out the influence of interindividual differences, we studied two individuals from whom cells were available before and after infection with HIV. Indeed, an increase in Th2 cytokine secretion was observed after HIV-infection. Loss of Th1 and enhanced Th2 responses might further curtail cellular responses resulting in deficiency of cellular immunity in HIV infection. PMID- 7994042 TI - Decreased macrophage colony-stimulating factor mRNA expression from activated cord versus adult mononuclear cells: altered posttranscriptional stability. AB - We have previously shown that protein production and mRNA expression of granulocyte-macrophage colony-stimulating factor (GM-CSF), granulocyte colony stimulating factor (G-CSF), and interleukin-3 are decreased in stimulated mononuclear cells (MNCs) from human umbilical cord compared with adult peripheral blood. These deficiencies may contribute to the increased susceptibility of neonates to infection. Macrophage colony-stimulating factor (M-CSF) regulates the proliferation, differentiation, and functional activation of monocytes. In the present study, we compared the regulation of M-CSF gene expression and protein production from stimulated cord and adult MNCs. Upon adhesion to tissue culture flasks, both cord and adult MNCs constitutively expressed M-CSF mRNA. In response to both adhesion and recombinant human GM-CSF (rhGM-CSF) stimulation for 120 hours, radioimmunoassays and bioassays showed that cord MNCs produced twofold to threefold less M-CSF protein compared with adult MNCs. Northern blot analysis also showed a fourfold decrease in M-CSF mRNA expression in both unstimulated and GM-CSF-induced cord versus adult MNCs. M-CSF mRNA expression in both cord and adult MNCs peaked between 16 and 24 hours and decreased to normal levels by 48 hours. We next determined the relative rates of transcription of the M-CSF gene by nuclear run-on assays in both cord and adult MNCs. The basal level signal of the M-CSF gene was similar between cord and adult MNCs. The transcriptional rate after stimulation with rhGM-CSF appeared to increase to a similar extent in both cord and adult MNCs (130% +/- 10% v 150% +/- 15%, C v A, n = 3, mean +/- SD). The comparative stability of M-CSF mRNA from cord versus adult MNCs was next determined by actinomycin D decay studies. The half-life of M-CSF mRNA from stimulated adult MNCs was 70 +/- 7.0 minutes (n = 4) compared with 47 +/- 2.8 minutes (n = 3) from stimulated cord MNCs (mean +/- SD, P < .05). To further determine the involvement of labile protein factors in posttranscriptional regulation, cord and adult MNCs were incubated with cycloheximide (CHX; 10 micrograms/mL). There was a significant increase in the induction of M-CSF mRNA by CHX treatment in both cord and adult MNCs. The increase of M-CSF mRNA induction by CHX was 2.5 times higher in cord MNCs compared with that in adult MNCs. These results suggest that there are one or more labile proteins that regulate M-CSF transcript stability in both cord and adult MNCs.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 7994040 TI - Identification of a specific HLA class II haplotype strongly associated with susceptibility to cyclosporine-dependent aplastic anemia. AB - Hematopoietic function of some aplastic anemia (AA) patients is dependent on the administration of cyclosporine (CyA). To investigate whether certain HLA class II genes are associated with susceptibility to such CyA-dependent AA, we determined the HLA class II alleles of 59 AA patients treated with CyA. Among 26 patients successfully treated with CyA, 13 required a small dose of CyA to maintain stable hematopoiesis. Of these 13 AA patients, 10 shared an HLA class II haplotype of DRB1*1501-DQA1*0102-DQB1*0602. None of the 13 responders who obtained a sustained remission off CyA therapy possessed this haplotype. In the 10 patients who shared the HLA class II haplotype, single-strand conformation polymorphism analysis of each gene fragment of this haplotype failed to detect a polymorphism in the nucleotide sequence. When the AA patients were assessed for their likelihood to respond to CyA therapy, the response rate in patients with this haplotype (71%) was significantly higher than that of patients with another haplotype associated with HLA-DR2, DRB1*1502-DQA1*0103-DQB1*0601 (36%) and that of patients without HLA-DR2 (35%). These findings indicate that the CyA-dependent response of AA is closely related to an HLA class II haplotype of DRB1*1501-DQA1*0102-DQB1*0602 and suggest that, in AA patients with this haplotype, immune mechanisms play an important role in the pathogenesis of bone marrow failure. PMID- 7994043 TI - Early myeloablative therapy for multiple myeloma. AB - The value of early myeloablative therapy supported by autologous bone marrow or blood progenitor cells was assessed in 72 patients with multiple myeloma who were treated within 1 year of initial therapy. Forty-five patients were consolidated during remission, and 27 patients were treated for primary refractory disease. Outcomes were compared with those of similar patients who did not receive intensive treatment primarily for socioeconomic reasons. Among patients who had responded previously, myeloablative therapy increased the rate of complete remission from 5% to 45% (P < .01) but did not prolong progression-free intervals or survival times. The same treatment controlled the myeloma in 70% of patients with primary resistant disease and prolonged the median survival from 37 to 83 months (P = .03). Intensive treatment for primary resistant myeloma administered later in the disease course resulted in significantly lower response rates and shorter progression-free intervals. Current myeloablative regimens supported by autologous stem cells appeared useful primarily in patients with primary resistant disease during the first year of therapy. PMID- 7994044 TI - Characterization of a vitamin D3-resistant human chronic myelogenous leukemia cell line. AB - A variant of the chronic myelogenous leukemia cell line, RWLeu-4, that is resistant to the antiproliferative effects of vitamin D3 was established. Although RWLeu-4 proliferation is inhibited by 1 nmol/L vitamin D3, the resistant cells (JMRD3) continue to proliferate in the presence of 100 nmol/L vitamin D3. Both cells express similar patterns of differentiation-specific antigens after treatment with vitamin D3, and both express the retinoblastoma gene product (p110Rb). Vitamin D3 treatment of the sensitive RWLeu-4 cells decreased the level of the p110Rb protein, as well as its phosphorylation. In contrast, vitamin D3 treatment of JMRD3 had no effect on p110Rb expression or phosphorylation. Both RWLeu-4 and JMRD3 express similar vitamin D3 receptors and vitamin D3-inducible enzyme activities. Differences were detected in the DNA binding characteristics of the vitamin D3 receptors as determined by electrophoretic mobility shift studies. However, sequence analysis of the DNA-binding domain and immunoblot analysis showed no differences in the receptors. We conclude that some process subsequent to vitamin D3 receptor activation is altered in JMRD3 that partially separates vitamin D3-induced inhibition of proliferation from the induction of differentiation. PMID- 7994045 TI - Abnormal expression of the p53-binding protein MDM2 in Hodgkin's disease. AB - The possible involvement of p53 tumor suppressor gene in the pathogenesis of Hodgkin's disease (HD) is suggested by the frequent finding of abnormal accumulation of p53 protein in the nuclei of Reed-Sternberg cells and their variants (H-RS) in a large proportion of cases. This finding, besides being consistent with the presence of p53 gene mutations, might represent a consequence of the inactivating interaction between p53 and p53-binding proteins such as the product of the MDM2 cellular oncogene. We have examined an unselected series of 77 HD cases of different histologic patterns for the expression of p53 and MDM2 proteins, using specific monoclonal antibodies and sensitive immunohistochemical techniques in single- and double-marker combination. In the large majority of cases (66/77), a variable proportion of H-RS cells expressed MDM2 that was strictly confined to the nuclei. Coexpression of both MDM2 and p53 was common in the same cells. The abnormal nuclear expression of p53 and MDM2 did not seem to correlate with the presence of Epstein-Barr virus infection, as shown by the results of LMP-1 antigen expression and EBER in situ hybridization analysis. Our data suggest that the abnormal accumulation of MDM2 and p53 proteins in HD might reflect a derangement of molecular mechanisms that could play a pathogenetic role in this disease. PMID- 7994047 TI - Immunomorphologic analysis of bone marrow biopsies after treatment with 2 chlorodeoxyadenosine for hairy cell leukemia. AB - Treatment of hairy cell leukemia with 2-chlorodeoxyadenosine (2-CdA) induces complete remissions in 85% of patients. Complete remission has been defined as the absence of hairy cells in the bone marrow after routine morphologic examination. To determine if hairy cells could be detected in complete remission bone marrows using immunohistochemical techniques with antibodies L26 (CD20) and DBA.44, 154 bone marrow biopsies performed between 3 months and 25 months after therapy were studied. Of the biopsies, 50% exhibited staining with L26 and/or DBA.44 in five or more cells with morphologic features of hairy cells. Minimal residual disease was usually less than 1% of the total cellular population. DBA.44-positive cells were demonstrated in 91% of the biopsies, although in 48% of these the morphologic features of the positive cells were not sufficiently distinctive for hairy cells. The proportion of biopsies with residual hairy cells was similar over the 25 months of follow up, indicating a relatively stable amount of residual disease. Immunomorphologic analysis is a more sensitive method for detecting residual hairy cells than morphology alone. Although further follow up is necessary to determine the clinical significance of the L26/DBA.44-positive staining in cells with and without distinctive morphologic features of hairy cells, we conclude that many patients in a stable clinical remission may have residual hairy cells. PMID- 7994046 TI - Nonrandom cytogenetic changes accompany malignant progression in clonal lines abelson virus-infected lymphocytes. AB - Initially, lymphoid cells transformed by v-abl or BCR/ABL oncogenes are poorly oncogenic but progress to full transformation over time. Although expression of the oncogene is necessary to initiate and maintain transformation, other molecular mechanisms are thought to be required for full transformation. To determine whether tumor progression in ABL oncogene-transformed lymphoid cells has a genetic basis, we examined whether progression of the malignant phenotype of transformed clones correlates with particular cytogenetic abnormalities. A modified in vitro bone marrow transformation model was used to obtain clonal Abelson murine leukemia virus-transformed B lymphoid cells that were poorly oncogenic. Multiple subclones were then derived from each clone and maintained over a marrow-derived stromal cell line for several weeks. Over time, clonally related Abelson murine leukemia virus-transformed subclones progressed asynchronously to full transformation. The data show that tumor progression can occur in the absence of detectable cytogenetic changes but, more importantly, that certain cytogenetic abnormalities appear reproducibly in highly malignant subclones. Therefore, three independent subclones showed deletion in a common region of chromosome 13. Other highly malignant cells carried a common breakpoint in the X chromosome, and, finally, two subclones carried an additional chromosome 5. These results are consistent with the hypothesis that ABL oncogenes are sufficient for the initial transformation of cells but that additional genetic events can drive oncogenic progression. These observations further suggest that diverse genetic mechanisms may be able to drive tumor progression in cells transformed with ABL oncogenes. PMID- 7994048 TI - Synergistic growth inhibitory and differentiating effects of trimidox and tiazofurin in human promyelocytic leukemia HL-60 cells. AB - Increased ribonucleotide reductase (RR) activity has been linked with malignant transformation and tumor cell growth. Therefore, this enzyme is considered to be an excellent target for cancer chemotherapy. We have examined the effects of a newly patented RR inhibitor, trimidox (3,4,5-trihydroxybenzohydroxamidoxime). Trimidox inhibited the growth of human promyelocytic leukemia HL-60 cells with an IC50 of 35 mumol/L. Incubation of HL-60 cells with 50 mumol/L trimidox for 24 hours decreased deoxyguanosine triphosphate (dGTP) and deoxycytidine triphosphate (dCTP) pools to 24% and 39% of control values, respectively. Incubation of HL-60 cells with 20 to 80 mumol/L trimidox even up to a period of 4 days did not alter the distribution of cells in different phases of cell cycle. Sequential incubation of HL-60 cells with trimidox (25 mumol/L) for 24 hours and then with 10 mumol/L tiazofurin (an inhibitor of inosine monophosphate dehydrogenase) for 4 days produced synergistic growth inhibitory activity, and the cell number decreased to 16% of untreated controls. When differentiation-linked cell surface marker expressions were determined in cells treated with trimidox and tiazofurin, a significantly increased fluorescence intensity was observed for the CD 11b (2.9 fold). CD 33 (1.9-fold), and HLA-D cell surface antigens. Expression of the transferrin receptor (CD71) increased 7.3-fold in cells treated with both agents, compared with untreated controls. Our results suggest that trimidox in combination with tiazofurin might be useful in the treatment of leukemia. PMID- 7994049 TI - Studies of human cord blood dendritic cells: evidence for functional immaturity. AB - We have isolated low-density, nonadherent, nonphagocytic, HLA-DR+ve cells with the morphology of dendritic cells (DCs) from the cord blood of full-term newborn infants. Relative to adult DCs, cord blood DCs were poor stimulators of the mixed leukocyte reaction when either adult or cord blood mononuclear cells (MNCs) or T lymphocytes were used as responder cells. In contrast, cord blood T cells and MNCs responded normally to allogeneic adult DCs. Cord blood DCs performed poorly as accessory cells for T-lymphocyte mitogenic responses at suboptimal concentrations of concanavalin A (Con A) and phytohemagglutinin A or at optimal concentrations of mitogen and low numbers of DCs. Addition of recombinant interleukin-2 (rIL-2) or recombinant interferon-gamma (rIFN-gamma) to cord blood DC-T-cell cultures containing a suboptimal concentration of Con A potentiated the proliferative response. In contrast, rIL-2 and rIFN-gamma exerted little effect on the proliferative response of adult T cells cultured with Con A and DCs. Flow cytometric studies showed that levels of intercellular adhesion molecule-1 (ICAM 1; CD54) and major histocompatibility complex (MHC) class I HLA-ABC and class II HLA-DR antigens on cord blood DCs were significantly lower than those on adult blood DCs. These findings suggest that the relative inefficiency of cord blood DCs in the activation of T cells may be related to their low cell surface expression of MHC and cell adhesion molecules. The demonstrated impairment of cord blood DC function could be of importance in understanding the immunologic relationship between the fetus and mother and could contribute to the susceptibility of newborns to infection. PMID- 7994050 TI - Molecular analysis of the structure and expression of the RH locus in individuals with D--, Dc-, and DCw- gene complexes. AB - Rh blood group antigens of the D, C/c, and E/e series are carried by at least three red cell membrane polypeptides encoded by two highly related genes, RHD and RHCE. Homozygous individuals carrying the D--, Dc-, and DCw- gene complexes are characterized by a total or partial lack of expression of the RHCE-encoded antigens. Analysis of the molecular genetic basis of these rare conditions indicates that complete or partial expression defect of Cc/Ee antigens result from different alterations at the RH locus, but not from gross deletions. No rearrangement or mutation of the RHCE gene could be detected in donors homozygous for the D-- complex, suggesting that the lack of the Cc and Ee antigens might result from a reduced transcriptional activity of the RHCE gene. The Dc- and DCw- gene complexes, however, exhibited an important rearrangement of the RHCE gene. Instead of the normal RHCE gene, both variants carried a hybrid RHCE-D-CE gene in which exons 4 to 9 (Dc- complex) and 2 (or 3) to 9 (DCw- complex) of the RHCE gene, respectively, have been substituted by the equivalent region of the RHD gene. These gene conversion events provide an explanation for the well-described abnormal antigen profiles associated with the Dc- and DCw- complexes, like the increased expression of RhD, the reduced expression of RhC/c or RhCw, and the absence of RhE/e. PMID- 7994051 TI - Rapid genotyping of the five major platelet alloantigens by reverse dot-blot hybridization. AB - Amino acid substitutions in platelet membrane glycoproteins result in alloantigens. Identifying these polymorphisms is important in alloimmune-mediated platelet disorders. Immunophenotyping platelet antigens can be limited by the unavailability of specific antisera. The goal of this work was to identify human platelet antigen genotypes in individuals using a technique that would circumvent the limitations of immunophenotyping and be clinically applicable. We have successfully applied the reverse dot-blot (RDB) technique to the genotyping of the five major human platelet alloantigen systems. Allele-specific oligonucleotides (ASOs) representing each allele of these alloantigens were covalently linked to a filter. Biotinylated oligonucleotides flanking the polymorphic sequences in genomic DNA were used to amplify genomic DNA by the polymerase chain reaction (PCR), and these products were hybridized to the filters containing the ASOs. Reactivity was detected with a chromogenic substrate. This nonradioactive methodology identifies all 15 possible genotypes in a well-defined control group of individuals and requires only two PCR reactions per patient sample. RDB analysis was used to successfully genotype women and family members with neonatal alloimmune thrombocytopenia and with posttransfusion purpura and to prenatally genotype the amniocytes from a fetus at risk for thrombocytopenia. The RDB methodology is specific, sensitive, and rapid and should enhance our ability to accurately diagnose disorders of alloimmune platelet destruction. PMID- 7994052 TI - Clonal dysregulation of the antibody response to tetanus-toxoid after bone marrow transplantation. AB - After bone marrow transplantation (BMT), a prolonged dysregulation of humoral immunity can be observed. In the present study, we investigated whether this is reflected in an abnormal production of specific antibodies (Ab) to the T-cell dependent recall antigen tetanus-toxoid (TT). The study group consisted of children receiving transplants of an unmodified allogeneic graft and of adults receiving either a T-cell-depleted allogeneic or an unmodified autologous BM graft. Findings were compared with those in healthy controls. In pediatric graft recipients, who were routinely revaccinated early after BMT, the Ab response was quantitatively superior to that in adult graft recipients who did not receive early revaccination. In the majority of graft recipients, the time period after vaccination required to reach the peak level of antibodies was prolonged and the number of responding TT-specific B-cell clones was markedly decreased in comparison with controls. In controls, a low frequency of dominant B-cell clones may produce low quantities of homogeneous Ab components (H-Ab) against a heterogeneous background. However, in BM graft recipients, "overshooting" of Ab production by separate B-cell clones was observed, resulting in the development of H-Ab at a relatively high concentration. These abnormalities were present up to 10 years after BMT, irrespective of either the age of the recipient, the modulation of the graft, or the vaccination schedule used. It is hypothesized that the dysregulated Ab production is the consequence of activation of a restricted number of resting memory B cells, present in germinal centers, repopulating gradually after BMT. Our data show that routine revaccination early after BMT improves the humoral immune response. However, because of a clonally dysregulated Ab production, long-lasting qualitative defects may be present even after normalization of Ab titers. PMID- 7994053 TI - Altered retinoid dose-response of retinoic acid-resistant HL-60 cells. PMID- 7994054 TI - Evidence that a second human tissue factor pathway inhibitor (TFPI-2) and human placental protein 5 are equivalent. PMID- 7994055 TI - Mixed chimerism after bone marrow transplantation and the risk of relapse. PMID- 7994056 TI - Interaction of primitive human myeloid and lymphoid progenitors with the marrow microenvironment. AB - Primitive human hematopoietic progenitors containing a high proportion of long term culture-initiating cells (LTCICs) are found in the 34+DR- fraction of bone marrow mononuclear cells (BMMNCs). These progenitors adhere selectively to the 33/66-kD binding domain of fibronectin and to the FN-CHII binding site, unlike more committed progenitors, which adhere less selectively to fibronectin components. These differences in adhesion to stromal components may explain selective homing and release of progenitors at varying levels of differentiation from the marrow compartment. In additional studies, we demonstrate that cultivation of primitive progenitors in a stroma noncontact long-term culture allows both differentiation of primitive progenitors and conservation of LTCICs. These observations (1) demonstrate that expansion of primitive progenitors does not require stromal contact, (2) shed light on the regulatory role of stroma in myeloid differentiation, and (3) suggest strategies for both ex vivo myeloid progenitor expansion and retrovirus gene insertion. Finally, we demonstrate that a natural killer cell population can be derived from primitive hematopoietic progenitors in a modified long-term culture model. Our findings suggest an important role for marrow stroma in lymphoid differentiation from primitive progenitors and in expression of CD2, a lymphoid marker ordinarily associated with passage of T-lymphocyte progenitors through the thymus. PMID- 7994057 TI - Gene transfer into hematopoietic stem cells. AB - The ability to insert a gene into hematopoietic stem cells and achieve lineage specific expression of the transferred gene within hematopoietic organs following bone marrow transplantation would create the potential to effectively treat many genetic and acquired diseases. The use of retroviral vectors to achieve this purpose has been investigated extensively in animal models and most recently, in humans. In the murine model, about 20-30% of repopulating stem cells can be genetically modified with a retroviral vector. Peripheral blood stem cells, mobilized by cytokine administration in splenectomized animals, are readily transduced and are capable of long-term reconstitution of transplant recipients with genetically modified cells. Similar protocols have been utilized to transduce highly purified stem cells from rhesus monkeys. Although long-term repopulation with cells that persistently express the transferred gene has been achieved, the frequency of cells containing the vector genome is only about 1-2%. Genetic marking of human bone marrow and peripheral blood cells has been utilized to investigate their potential for contributing to long-term reconstitution following autologous transplantation. Future work will focus on improving gene transfer efficiencies for specific therapeutic applications. PMID- 7994058 TI - Rheologic and pathophysiologic significance of red cell passage through narrow pores. AB - To elucidate the pathophysiologic significance of red blood cell (RBC) filterability, we measured RBC rheology with our own designed nickel mesh with 3 microns pores, smaller than the previously used 5-microns pores. Vertical and cylindrical pores with no pore coincidence were regularly distributed across the filter, the pore entrances of which showed a round and rather smooth transition to the pore inside. An advantage of the nickel mesh is the repeated use (at least 100 times) of the same filter possible after ultrasonic washing. A very low concentration of RBC, i.e., 3 x 10(4) cells per cubic millimeter (hematocrit value of approximately 0.3%), was sufficient for a typical test to examine RBC filterability. The filtration of the dilute RBC suspension was not influenced by contaminating or added leukocytes up to a leukocyte count of approximately seven cells per cubic millimeter; therefore, measurements can be performed using conventionally washed RBCs. This may be practically relevant to routine use, such as in a clinical laboratory. As compared with filtration through 5-micron pores, filtration through 3-micron pores was found to be very sensitive in detecting major determinants of RBC deformability, particularly, changes in viscoelastic properties of the cell membrane, surface area/volume ratio of the cell, perturbing effects of lysophosphatidylcholine, and osmolality of the medium. The 3-micron filtration method revealed a marked impairment in the filterability of Heinz body-containing RBCs from patients with unstable hemoglobin (Hb) disease (Hb Yokohama). Thus, 3-micron-filtration measurements may contribute to several subfields of hematology. PMID- 7994059 TI - In vivo polymerization of sickle-cell hemoglobin: a theoretical study. AB - Several studies on the gelation and oxygenation state of sickle red blood cells have been done under conditions of equilibrium. The kinetics of sickle hemoglobin (HbS) polymerization have also been studied extensively in fully deoxygenated HbS solutions. The issue of the relevance of these investigations to the physiological in vivo situation has not been addressed. Here, we use a theoretical model to compare theoretical equilibrium predictions of HbS polymer concentration and cellular oxygen content, previously validated against equilibrium data, with the corresponding values under physiologic oxygen unloading conditions. We also use the model to simulate polymerization in almost completely deoxygenated sickle erythrocytes, validate the theoretical polymerization curves against published data, and compare them with the corresponding curves from the dynamic oxygen unloading analyses. Our model shows that equilibrium predictions severely overestimate intracellular polymer concentrations and underestimate cellular oxygen content, during the unloading of oxygen. Also, the delay times to significant polymerization in the physiologic situation are substantially longer than the corresponding values measured in completely deoxygenated HbS solutions. These results indicate that in vivo HbS polymerization is strongly influenced by the rate of oxygen desaturation. Equilibrium estimates of intracellular polymer content, or polymerization kinetic data from fully deoxygenated solutions, could be misleading and should be used in the proper perspective. PMID- 7994060 TI - Development of hemopoietic bone marrow within the ectopic bone induced by bone morphogenetic protein. AB - Neogenesis of hemopoietic bone marrow was observed in the ectopic bone induced by implantation of bone morphogenetic protein (BMP) into the muscle of mice. A bone rudiment-like cartilage was formed first, which was then replaced by bone through an endochondral ossification process. Bone marrow formation occurred after the invasion of blood vessels into the cartilage, with accumulations of small lymphocyte-like cells and the appearance of large hemopoietic stem cells around the blood vessels. The stem cells proliferated and differentiated to form hemopoietic bone marrow. This process was similar to the embryogenesis of bone and bone marrow, but the hemopoietic activity of the BMP-induced bone was transient. The bone marrow was converted to fatty tissue within 2 weeks of its appearance. This study showed that implantation of BMP in the ectopic sites offers a useful model to investigate the neogenesis of ectopic bone marrow and the regulation of its activity. PMID- 7994061 TI - Lysis of blood platelets by human osteosarcoma cells in vitro. AB - The in vitro interactions between human osteosarcoma (HOS) cells and platelets were studied in real time using video-enhanced microscopy. Interference reflection techniques showed that platelets were lysed within minutes after contacting HOS cells that had been treated with interferon-gamma. Untreated HOS cells lysed platelets less efficiently. Platelet lysis depended on platelet-tumor cell contact and on extracellular Ca2+. A number of possible mechanisms were excluded. Lysis of platelets in proximity to tumor cells can provide these with growth factors and thereby contribute to the metastasis-enhancing effect of platelets. PMID- 7994062 TI - Protein tyrosine phosphorylation in the regulation of hematopoiesis by receptors of the cytokine-receptor superfamily. AB - Cytokines regulate the growth and differentiation of hematopoietic cells through their interaction with receptors of the cytokine receptor superfamily. This family of receptors has conserved motifs in the extracellular domain but share only limited similarity in the cytoplasmic domains. Although lacking catalytic domains, a variety of studies demonstrate that the cytokine receptors function by coupling ligand binding to induction of tyrosine phosphorylation. Recent studies have shown that the JAK family of kinases associate with cytokine receptors and are activated by ligand binding. Interaction occurs with the membrane proximal region of the cytoplasmic domain, a region that has been found to be essential for mitogenesis. One of the substrates of tyrosine phosphorylation is the receptor and, in the case of the receptor for Epo, the membrane distal region of the cytoplasmic domain is phosphorylated. Once phosphorylated, this site becomes a binding site for the amino-terminal SH2 domain of hematopoietic cell phosphatase (HCP). HCP is an important negative regulator of hematopoietic cell growth and its recruitment to the receptor complex is speculated to be important for this effect. The role of HCP is best indicated by the observation that the murine mutation, motheaten, is due to a mutation that results in the inability to make HCP. Motheaten mice die soon after birth due to the overproliferation of a variety of hematopoietic lineages. Together the results demonstrate an essential role in both protein tyrosine phosphorylation and de-phosphorylation in the growth regulation of hematopoiesis. PMID- 7994063 TI - Enrichment for primitive hemopoietic progenitors of marrow cells from 5 fluorouracil-treated mice and normal mice. AB - Study of the mechanisms regulating stem cells would be significantly facilitated if a purified population of stem cells were available. During the last 4 years, our laboratory has been engaged in enrichment of murine marrow cells for primitive hemopoietic progenitors. We primarily used marrow cells from mice treated with 150 mg/kg of 5-fluorouracil (5-FU), and our assay for the primitive progenitors was formation of multilineage colonies supported by a combination of interleukin-3 (IL-3) and IL-6. First, we found that post-5-FU marrow cells with a density of 1.0631-1.0770 g/cm3, negative for lineage-specific markers and positive for Ly-6A/E are routinely enriched for multipotential progenitors by approximately 800-fold. We then observed that J11d.2 and c-kit are additional useful markers for further enrichment of the primitive hemopoietic progenitors. Cell cycle-dormant primitive progenitors are primarily in the J11d.2+ fraction, whereas more mature progenitors are J11d.2-. The primitive progenitors express relatively low levels of c-kit, while more mature, actively cycling progenitors express high levels of c-kit. Combinations of these markers may be useful in enrichment of marrow cells of normal mice for primitive hemopoietic progenitors. PMID- 7994064 TI - Differential manipulation of normal and chronic myeloid leukemia stem cell proliferation in vitro. AB - The long-term marrow culture (LTC) system allows the sustained production of primitive normal and neoplastic (chronic myeloid leukemia [CML]) hematopoietic cells in vitro for many weeks. This is achieved in the absence of exogenously added hematopoietic growth factors because of the presence in the cultures of supportive "stromal" cells of the fibroblast-endothelial-adipocyte lineages. These latter cells form a confluent adherent layer with which the most primitive hematopoietic cells become associated and which locally regulates their behavior. The LTC system has thus been considered as a model of the microenvironment of the bone marrow and used to delineate potentially physiologically relevant mechanisms that regulate the proliferation, self-renewal and differentiation of primitive normal hematopoietic cells. It has also been used to analyze the molecular basis of the altered proliferative behavior that characterizes primitive neoplastic cells from patients with CML. Most of the information obtained to date has emerged from experiments designed to shift the balance of stimulatory and inhibitory factors present in order to favor either the cycling or quiescence of primitive normal or CML cells in LTC. This has been achieved either by addition of soluble factors (or antagonists) to the LTC medium or by the use of genetically engineered factor-producing stromal cells. Such experiments have allowed the identification of a number of cytokines that promote one or the other of these responses (i.e., primitive progenitor cycling or quiescence), including some that are involved in control mechanisms endogenous to the LTC system. Recent studies suggest that the retention of primitive normal cells in a reversible G(o) state in this system is mediated by the cooperating action of limiting concentrations of at least two endogenously produced inhibitory factors (transforming growth factor-beta (TGF-beta) and macrophage inflammatory protein-1 alpha (MIP-1 alpha)), either of which, however, if added exogenously at a sufficient concentration, can exert this action on its own. Interestingly, the heightened turnover characteristic of primitive CML cells appears to be due to a selective unresponsiveness to only one of these two inhibitors (MIP-1 alpha). These findings are consistent with a complex model of the extrinsic regulation of primitive hematopoietic cells in which a multiplicity of intracellular signaling intermediates within the target cells converge at different points ultimately to control their entry into S phase. Our findings further suggest that only some of these pathways may be affected by intracellular expression of the BCR-ABL fusion gene. PMID- 7994066 TI - Optimizing performance through process improvement. AB - Health care professionals have found traditional problem solving and traditional management have not succeeded in "assuring quality." Organizations are changing the way they do business and are utilizing process improvement methodology to improve performance. Based on important functions, select dimensions of performance for processes are measured, evaluated, redesigned, and improved. Once priorities for improvement activities are determined, improvement projects can be implemented utilizing various process improvement models. The PRIDE (process, relevant, interpret, design, execute) model, designed by the authors, is one approach that can be applied in any setting. PMID- 7994065 TI - In vitro and in vivo studies of stromal niches. AB - Lymphohematopoiesis occurs in the densely packed environment of the intramedullary spaces. Primitive lymphohematopoietic stem cells exist in close apposition to a variety of supportive cells including both hemopoietic and nonhemopoietic lineages. Using an in vitro long-term Dexter liquid culture system, we have established that a variety of cytokines are produced constitutively by such stromal cells in culture. These cytokines include Steel factor, interleukin-6 (IL-6), and colony-stimulating factor (CSF-1). Granulocyte CSF and granulocyte-macrophage-CSF mRNA can be detected after refeeding of cultures, although in quiescent cultures message for these factors is difficult to detect. Interleukin-3, IL-4, and IL-5 are not detectable by standard Northern blot analysis or bioassay of condition media. However, IL-3--detectable by reverse-transcriptase PCR and biologic activity--was confirmed by growth of factor-dependent cells on stromal cells with IL-3 antibody blocking of such growth. Stem cells resident on such stromal cells are mirrored by the high proliferative potential colony-forming cell assay and are responsive to a relatively large number of cytokines, with Steel factor being of central importance, appearing to be a critical component of various synergistic combinations. Steel factor allows reduced levels of other factors in such combinations and works early in a temporal sequence. Hematopoietic stem cells can engraft in normal nonmyeloablated hosts. Using a male/female BALB/c transplantation model, we have shown high rates of engraftment into normal animals, out after marrow infusion to 25 months, after marrow infusion and that post-5-fluorouracil bone marrow is quite deficient in such engraftment.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7994067 TI - Improving the process of communication at the bedside. AB - Timely communication among health care workers, patients, and significant others is an important component of delivering quality health care. As patients' lengths of stay decrease, "flextime" among health care personnel increases, and the various types of practitioners providing patient care increases, a method for quick communication of pertinent clinical information at the bedside becomes imperative. A multidisciplinary quality improvement team was formed to improve the process of communication of pertinent clinical information such as allergies, isolation precautions, and NPO (nothing by mouth) at the bedside. The outcome of this project was the development of a bedside clinical communication system and an improvement in the process of communicating pertinent clinical information at the bedside. PMID- 7994068 TI - Product evaluation and process improvement. AB - This article discusses how a systematic approach to product selection and evaluation can assist health care personnel. This model considers four tenets: (1) quality, (2) cost, (3) safety, and (4) practitioner choice. An algorithm is utilized to serve as a visual guide for the introduction, trial, and selection of equipment and products. In addition to considering the four tenets, the article discusses the value of an integrated team approach and the importance of involving the staff in the decisions. PMID- 7994069 TI - TQM brings collaboration to patient transport process. AB - Total quality management (TQM) principles can be utilized to achieve successful outcomes of an interdepartmental problem-solving process prior to implementation of a TQM formal structure within an organization. Prior to implementation of the new process, patient transport time from nursing units to lab destination was calculated at 17.6 minutes; postimplementation, an institutional benchmark of 15.4 minutes has been set. The mechanisms utilized for development, implementation, and evaluation of a process improvement team is the focus of the article. The reader will be taken on a journey through an interdepartmental problem-solving process utilizing the TQM principles. PMID- 7994070 TI - Improving patient outcomes in a dialysis unit: an integrated approach to CQI. AB - Continuous quality improvement (CQI), staff education, and patient education are essential, interrelated components of nursing practice that share the common goal of improved patient outcomes. The nurses of the Nashville Veterans' Administration Medical Center dialysis unit effectively combined these activities to improve the iron balance, hemoglobin, and hematocrit levels of chronic hemodialysis patients on erythropoietin. The integration of these components increased the effectiveness of each one, thereby enhancing the improvement of patient outcomes. PMID- 7994071 TI - Improving medication administration through an enhanced occurrence reporting system. AB - Accurate data about medication errors are essential to prevention efforts. A multidisciplinary team at Bon Secours Hospital trialed an innovative method of reporting medication errors. It increased the number of reported medication errors six times compared with the same time period for the previous year on the pilot unit. It also saved time for the person reporting the error. The continuous quality improvement methodology was used to implement the new process. PMID- 7994072 TI - The components of hospital quality: a nursing perspective. AB - The first stage of a larger investigation intended to define objective and standardized measures of the quality of care provided by hospitals included the conduct of focus groups with registered nurses, eliciting their opinions as to the merit of a number of potential indicators of hospital quality. The registered nurses in the focus groups settled on the ratio of registered nurses to beds, the percentage of board-certified physicians, the presence of discharge planning services, service mix, the number of technological services, and Council on Teaching Hospitals membership as the best indicators of high-quality care delivery. PMID- 7994073 TI - Process standards of nursing care for patients with COPD: validation of standards and criteria by the Delphi technique. AB - It is common for professional literature to describe quality of care as based on standards. Yet little attention is given to the steps that precede the establishment of these standards. This study answers the question. "Which nursing care standards and criteria should be developed for chronic obstructive pulmonary disease (COPD) patients discharged from a pulmonary rehabilitation center? "Our approach included the following steps: delineating the scope of care and service, identifying indicators, and formulating standards and identifying criteria. Aspects of care included are: establishment and maintenance of a good care relationship with the patient; delineation of the care needs during the home visit; provision of health education, advice, and instruction; support in psychosocial problems; and coordination and continuity of the service. These standards and criteria were validated by the Delphi technique. PMID- 7994074 TI - Influencing groups who choose to study or measure issues that seem to have little importance or relevance. PMID- 7994075 TI - Murine PGK-1 promoter drives widespread but not uniform expression in transgenic mice. AB - Pgk-1 is an X-linked gene encoding 3-phosphoglycerate kinase, an enzyme necessary in every cell for glycolysis. The regulatory sequences of the Pgk-1 gene were used to drive the E. coli lacZ reporter gene and 2 strains of transgenic animals created with this Pgk-lacZ transgene carried on autosomes. The levels of expression of Pgk-1 varied from one adult tissue to another and the transgene was similarly regulated. However, in situ staining of the beta-galactosidase encoded by the transgene indicated extensive cell-to-cell variability in its level of expression. A reproducible subset of cells stained darkly for the transgene product. Some of these beta-galactosidase positive cells were rapidly proliferating while others appeared to be metabolically very active, suggesting that the Pgk-1 promoter is regulated so as to be more active in cells requiring high levels of glycolysis. Although Pgk-1 is X-linked and subject to X chromosome inactivation, the transgenes were not inactivated in either female somatic or male germ cells. Thus, the Pgk-1 promoter drives transgene expression in all tissues but the levels of expression are not uniform in each cell. PMID- 7994076 TI - Type II collagen is transiently expressed during avian cardiac valve morphogenesis. AB - We present new evidence of the temporal and spatial expression of type II collagen in the embryonic chick heart during the very early stages of its development. In particular, we emphasize the distribution of its mRNA and protein during valve formation. Type II collagen as well as several other fibrillar collagens (types I, III, and V) are present in stage 18 endocardial cushion mesenchymal cells. At stage 23, alpha 1 (II) collagen transcripts and the cognate polypeptide colocalize in the atrioventricular valves. As development proceeds, the relative abundance of alpha 1 (II) collagen transcripts decreases during the stages studied (stages 22 to 45; day 3.5 to day 19) as assayed by RNA blotting of extracts of whole hearts. Type II collagen protein was immunologically undetectable in stage 38 (day 12) hearts, although collagens I, III, and V persisted and localize in the valve regions, in the endothelial lining of the heart, and in the epicardium. In keeping with other observations of type II collagen expression in non-chondrogenic regions of a variety of vertebrate embryos, the avian heart also exhibits transient type II collagen expression. PMID- 7994077 TI - Developmental regulation of M-cadherin in the terminal differentiation of skeletal myoblasts. AB - Cadherins form a large family of membrane glycoproteins which mediate homophilic calcium-dependent cell adhesion. They are thought to mediate the initial calcium dependent cell adhesion which precedes the plasma membrane fusion of skeletal myoblasts. Two cadherin subtypes are known to be expressed in mammalian skeletal myoblasts: muscle cadherin (M-cadherin) and neural cadherin (N-cadherin). In the present study we demonstrate that 1) the expression of M- and N-cadherin is differentially regulated during myoblast differentiation in vitro, 2) the expression of M-cadherin but not N-cadherin is inhibited by 5-bromo-2' deoxyuridine (BUdR), an agent which selectively inhibits skeletal myoblast differentiation, and 3) fusion and differentiation-competent rat L6 myoblasts do not express detectable levels of N-cadherin mRNA. In vivo, M-cadherin mRNA was detectable exclusively in skeletal muscle. M-cadherin mRNA levels peaked during the secondary myogenic wave in rat hindlimb muscle, becoming barely detectable in 1-week-old and adult rats. These observations indicate that M-cadherin is unique in two ways: It is the first cadherin to be included in the family of skeletal muscle-specific genes, and it shows peak levels of expression in developing skeletal muscle tissue. Taken together, these results suggest that M-cadherin plays an important role in skeletal myogenesis. PMID- 7994078 TI - Heart specification in the Mexican axolotl (Ambystoma mexicanum). AB - The concept of the morphogenetic field has been used extensively in developmental biology. However, little is known about the mechanisms that partition these broad areas of tissue into the smaller areas which actually form the corresponding structures, and the remaining tissue. In the Mexican axolotl, the heart field forms as the anterior lateral plate mesoderm migrates over the underlying pharyngeal endoderm between stages 14 and 28. We have previously shown that both the mid-ventral and lateral walls of the pharyngeal cavity have considerable inductive capacity at stage 14. If this inductive capability, and the competence of the mesoderm to respond, is retained between stages 14 and 28, a much broader area of mesoderm would be induced than actually participates in heart development. In this paper, we use explant cultures to establish that pharyngeal endoderm retains its inductive activity, and that both pre-cardiac mesoderm and lateral plate mesoderm caudal to the pharyngeal cavity remain competent to respond to the induction throughout this period. We also map the specified region of the antero-lateral mesoderm between stages 14 and 28 by placing carefully measured areas of mesoderm in culture without inductive endoderm. We found that the region capable of initiating a spontaneous beat approximately doubles in size during this period. Since the specified region is larger than the actual heart primordium, some mechanism must exist to partition "induced" mesoderm into heart forming and non-heart-forming areas.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7994079 TI - Elastic extracellular matrix of the embryonic chick heart: an immunohistological study using laser confocal microscopy. AB - The "elastic matrix" constitutes a specialized component of the extracellular matrix which confers resiliency to tissues and organs subjected to repeated deformations. The role of the elastic matrix in living organisms appears to be of key importance since diseases characterized by expression of defective inherited genes which encode components of the elastic matrix lead to premature death. While the elastic matrix of adult organs has received a great deal of attention, little is known about when it first appears in embryonic tissues or its possible role in developing organs. In the present study we have performed an immunohistochemical study of the distribution of elastin and three additional components often associated with elastic matrices in adult tissues (i.e., fibrillin, emilin, and type VI collagen) during the development of the chicken embryonic heart. The three-dimensional arrangement of these components was established through the observation of whole-amount specimens with scanning laser confocal microscopy. Our results revealed three different periods of heart development regarding the composition of the elastic matrix. Prior to stage 21 the embryonic heart lacks elastin but exhibits a matrix scaffold of fibrillin and emilin associated with the endocardium and the developing cardiac jelly. Between stages 22 and 29 the heart shows a transient elastic scaffold in the outflow tract which contains elastin, fibrillin, and emilin. Elastin-positive fibrillar material is also observed during these stages in the base of the atrioventricular cushion adjacent to the myocardial wall. In addition, emilin-positive material appears to be associated with the zones of formation of ventricular trabeculae. Collagen type VI was not detected during these early stages. From stage 30 to stage 40 a progressive modification of the pattern of distribution of elastin, fibrillin, emilin, and collagen type VI is observed in association with the formation of the definitive four-chambered heart. The distribution of the elastic scaffold in the outflow tract appears to be rearranged and becomes restricted to the roots of the main arteries. Each of the components studied here is also deposited at increasing levels in the developing valvular apparatus including the valve leaflets and the chordae tendinea. The components are also present in the subendocardial space where they form aligned fibrillar tracts, an arrangement suggestive of a role in ventricular contractile function. The epicardium constitutes an additional region of elastic matrix deposition during these later stages and contains elastic, fibrillin, and collagen type VI.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 7994080 TI - Developmental regulation of fatty acid binding protein in neural tissue. AB - Fatty acid binding proteins (FABP) constitute a family of small, cytosolic carriers of hydrophobic ligands. These proteins are thought to be important for lipid trafficking toward specific metabolic pathways, and are potentially important for the establishment of characteristic lipid compositions of neural tissue. In the embryonic chick retina and brain, FABP resembles the heart subtype, as determined by protein characterization and immunoblot studies. In this paper, the developmental expression and cellular localization of chick retinal FABP were examined. Results of immunoblot analysis suggest that FABP is maximally expressed around embryonic day 9 (E9) and declines thereafter. In adult retinas, FABP is barely detectable on a Western blot. Immunohistochemical staining of the retina shows light labeling on day E6 and a more intense staining throughout the retina on day E9. As the retina differentiates, labeling becomes increasingly localized. By day E18 subpopulations of ganglion cells and photoreceptor inner segments are stained, as are all photoreceptor cell bodies, most of the inner nuclear layer, and the nerve fiber layer. Staining is decreased in older retinas such that in adult animals, only light staining of the photoreceptor cell bodies is visible. The decrease in relative amount of FABP in the retina after day E9 suggests a role for FABP in the early stages of retinal differentiation. Localization in the retina is consistent with this hypothesis, as label becomes more restricted to those cells undergoing maturation at a particular developmental age. Thus, in young embryos (E6-E9), FABP immunolabeling is apparent throughout the retina, and transiently localizes at different ages (E12-E15) to plexiform and nuclear layers.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7994081 TI - Retarded chondrogenesis in transgenic mice with a type II collagen defect results in fracture healing abnormalities. AB - We have examined the biological and biomechanical consequences of defective type II collagen production for fracture repair employing a genetically engineered mouse line Del1 which was generated by microinjection of a 39-kb mouse pro alpha 1(II) collagen gene construct containing a deletion of exon 7 and intron 7 (Metsaranta et al. [1992] J. Cell Biol. 118:203-212). Standardized tibial fractures were produced in transgenic Del1 mice and their nontransgenic littermates were used as controls. The fracture callus tissues were analyzed at days 7, 9, 14, 28, and 42 using radiography, histomorphometry, biomechanical testing, and Northern analysis of mRNAs for several tissue-specific matrix components. Deficient production of cartilage in Del1 mice resulted in reduced radiographic callus size, smaller cross-sectional area, and impaired biomechanical properties when compared with fractures of nontransgenic control mice. The differences were most evident in 14-day fracture calluses. Consequently mRNAs for cartilage-specific type IX and X collagens and aggrecan were also reduced in Del1 calluses. Levels of type II collagen mRNAs were unaffected since the mutated transgene produced additional type II collagen mRNA molecules. Further abnormalities in the fracture repair process of Del1 mice were observed in callus remodeling. In the control animals a typical feature of external callus remodeling was reduction of callus size during endochondral ossification between days 14 and 28. Such reduction was not observed in the transgenic mice. Histological examination of fracture calluses suggested also a reduction in trabecular surface area, which was found to be even more pronounced in metaphyseal bone of Del1 mice. Despite these differences the biomechanical properties of the calluses in the two groups became similar by day 28 of fracture healing. The results thus suggest that reduced chondrogenesis due to the presence of mutated transgenes in Del1 mice not only causes a temporary impairment in biomechanical properties of healing fractures but also affects later stages of callus remodeling. PMID- 7994082 TI - Effects of retinoic acid and dexamethasone on proliferation, differentiation, and glucocorticoid receptor expression in cultured human osteosarcoma cells. AB - HOS-8603 is a newly established human osteosarcoma cell line with phenotypic characteristics of osteoblasts. When these cells were grown in monolayer culture in the presence of dexamethasone (Dex) or retinoic acid (RA), there was a significant inhibition of proliferation in a concentration-dependent manner. The combined effects of Dex and RA depended upon the concentrations: at low concentrations (< 10 nM) the effects of Dex and RA were additive, whereas at high concentrations the effects were antagonistic. Anchorage-independent growth studies performed in methylcellulose culture indicated that Dex or RA inhibited colony formation by HOS-8603 cells. Treatment of HOS-8603 cells with 100 nM Dex induced alkaline phosphatase activity in a time-dependent manner, reaching a maximum of about 6.5-fold over basal levels. All these effects of Dex on HOS-8603 cells could be reversed by RU 486, a potent antiglucocorticoid. Based upon saturation of specific binding and Scatchard plot analysis, we demonstrated that a saturable, high-affinity glucocorticoid receptor (GR) existed in HOS-8603 cells, suggesting that the effects of glucocorticoids on HOS-8603 cells are mediated by the specific GR. Finally, we further investigated the homologous and heterologous regulation of GR in HOS-8603 cells. Treatment of these cells with Dex led to a time-dependent decrease in GR concentrations. This homologous GR downregulation occurred not only at the level of hormone binding but also at the level of GR mRNA. In contrast, RA was capable of increasing GR concentrations in a concentration- and time-dependent manner.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7994083 TI - Analysis of MRP gene expression and function in HL60 cells isolated for resistance to adriamycin. AB - In an effort to define clearly the basis of non-P-glycoprotein multidrug resistance in HL60/ADR cells, we have analyzed expression of MRP mRNA levels and the MRP-encoded protein in resistant cells and also in resistant cells that have undergone a reversion to drug sensitivity. The results demonstrate that an MRP cDNA containing 5'-end coding sequences reacts with a 6-kb RNA, which is overexpressed in the resistant isolate. As resistant cells revert to drug sensitivity there is essentially a complete loss of the 6-kb RNA. Southern blot analysis indicates that the MRP gene is amplified compared to the copy number found in sensitive cells. Revertant cells no longer contain amplified MRP sequences. Western blot analysis has been conducted using an antibody prepared against the carboxyl terminus (15 amino acids) of the deduced sequence of the MRP encoded protein. The antibody is reactive with a 190-kDa protein (P190) and with two closely migrating proteins of 65 and 70 kDa (P70), which are overexpressed in plasma membranes and endoplasmic reticulum of resistant cells. Both proteins are greatly reduced in revertant cells. Growth of cells in the presence of tunicamycin demonstrates that both P190 and P70 are glycosylated, with the deglycosylated forms migrating in polyacrylamide gels as proteins of 165 kDa and 45 kDa, respectively. Additional antisera have also been prepared against sequence domains contained in the C-terminal region of P190. These antisera are reactive with both P190 and P70. Antisera directed against sequences of the amino terminal region of P190 do not react with P70.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7994084 TI - Analysis of O6-methylguanine-DNA methyltransferase in individual human cells by quantitative immunofluorescence microscopy. AB - A quantitative assay of immunofluorescence is described that can be performed on individual cells from standard pathologic specimens using fluorescence microscopy. The technique has been applied to measurement of O6-methylguanine-DNA methyltransferase, a DNA repair protein that is a molecular marker for resistance to chloroethylnitrosources used in cancer chemotherapy. The immunofluorescence assay makes use of monoclonal antibodies with specificity for human transferase, fluorescence microscopy with digital imaging, fluorescent bead internal standards, and computerized image analysis. This method is specific for the transferase, produces results correlated with activity measurements, and yields new data about tissue heterogeneity and subcellular localization previously unavailable with standard assay methods. PMID- 7994085 TI - The FGF-4 promoter is required for transformation and is active in both embryonal and somatic cells. AB - We report the independent isolation of a rearranged FGF-4 gene from a patient with chronic myeloid leukaemia. We show that the FGF-4 gene has been truncated 30 nucleotides 3' to the coding sequence and has been fused to the RNA processing signals from a putative unknown gene on chromosome 15. We demonstrate that the promoter region of the FGF-4 gene is active in NIH3T3 cells and is indeed necessary for transformation. Using the luciferase reporter assay we have shown that the FGF-4 5' flanking sequences possess easily detectable promoter activity in both F9 and HeLa cell lines. 5' deletion analysis of the FGF-4 promoter has delineated regions containing cis-acting elements of functional importance. These regulatory regions are common to both embryonal and somatic cell lines. Electrophoretic mobility shift assay, using nuclear extracts from F9 and HeLa cells, has allowed detection of DNA-protein interactions occurring in the functionally significant regions. Subsequent comparison of the human and murine FGF-4 promoters show that the regions of functional significance are highly conserved. We suggest that the FGF-4 gene may be suppressed through a distal suppressor locus and becomes active when separated from this suppressor. PMID- 7994087 TI - Reference listings in cancer research. PMID- 7994086 TI - Modulation of intrinsic in vitro resistance to carboplatin by edatrexate in the A549 human nonsmall cell lung cancer cell line. AB - Edatrexate (10-ethyl-deazaaminopterin) is a methotrexate analog that has been shown to have greater antitumor activity and improved therapeutic index compared to its parent compound in preclinical systems. We have evaluated the ability of edatrexate to modulate the intrinsic resistance of the lung adenocarcinoma A549 cell line to carboplatin. Concentration effects, exposure time and schedule dependence were assessed. Modulation of resistance was observed with edatrexate treatment (0.2 microM for 1 h) prior to carboplatin. The concentrations of carboplatin to achieve IC50 at the 1-, 3-, and 24-h IC50 were decreased by a mean of 16.8 times (12.2-22.2) with edatrexate preexposure. In contrast, there was little modulation observed of carboplatin resistance when carboplatin was administered prior to edatrexate. In addition, schedule dependency experiments were performed using the method described by Chou and Talalay, in which the ratio of carboplatin to edatrexate was constant or nonconstant, and both the potency of effects and the shapes of the concentration-effect curves were taken into account in a computerized analysis. These experiments also demonstrated schedule dependency. Although both treatments resulted in a reduced IC50 vs. carboplatin alone, the reduction was much greater when edatrexate was added first (12.59 vs. 2.59 times). We conclude that the combination of edatrexate and carboplatin demonstrates schedule-dependent modulation of intrinsic carboplatin resistance in this in vitro model at clinically achievable edatrexate plasma levels (0.01 to 10 microM). The greatest modulatory synergism was observed in the setting of edatrexate treatment before carboplatin. Our findings suggest a potentially useful schedule when combining edatrexate and carboplatin for the treatment of malignant disease. PMID- 7994088 TI - Proceedings of the aortic surgery symposium IV. New York, New York, April 21-22, 1994. PMID- 7994089 TI - Three faces of the Bentall procedure. AB - Since the original description of composite replacement of the aortic valve and ascending aorta by Bentall in 1968, several modifications of the technique have been described. In order to evaluate the results of these different techniques, we have retrospectively reviewed our results with 140 consecutive patients who underwent Bentall operations between October 1986 and March 1994, using three different anastomotic techniques: Classic, n = 30; Button, n = 95, and Cabrol, n = 15. Overall hospital mortality was 5%. In univariate analysis, acute type A dissection, rupture, new preoperative neurological symptoms, and the Cabrol technique were associated with a higher hospital mortality, but by multivariate analysis no independent risk factors were demonstrated. Overall rates of reoperation did not differ among the three techniques (Classic 4.1%/pt-yr, Button 2.7%/pt-yr, Cabrol 0%/pt-yr; p = 0.44). The actuarial freedom from reoperation was 87% at 5 years. The 5-year actuarial survival for all patients was 79% (Classic 85%, Button 82%, Cabrol 52%): the poorer results with the Cabrol modification are likely due to patient selection, complicated by a higher early mortality in this small group of patients. The presence of dissection was associated with a higher mortality in Marfan patients (50% vs 8%, p = 0.03). The rate of aortic valve-related complications was 3.6%/pt per year. Actuarial event free survival was 67% at 5 years. Current indications for an elective Bentall procedure include an ascending aortic diameter of 6 cm or greater, with significant aortic valvular dysfunction, and dilatation of the ascending aorta greater than 5 cm in patients with Marfan syndrome or a bicuspid aortic valve. The routine procedure of choice is the Button Bentall technique, with the Classic Bentall and the Cabrol variation reserved for use under special circumstances. PMID- 7994090 TI - Composite graft repair of Marfan aneurysm of the ascending aorta: results in 150 patients. AB - One hundred fifty consecutive Marfan patients undergoing composite graft repair of an ascending aorta aneurysm are reported. Twenty-six of the 150 patients had a preoperative dissection of the ascending aorta. There were no early deaths among 138 patients undergoing elective composite graft repair. There was one early death among 12 patients undergoing urgent operation; this patient arrived at the hospital with a rupturing aneurysm. Twenty-four of the 150 patients had mitral procedures; there were no early deaths in this group. There have been 14 late deaths among the 149 hospital survivors (9%). Actuarial survival of 150 patients at 1, 5, 10, and 14 years was 93%, 92%, 81%, and 73% respectively. Risk factors for early or late death were identified by multivariate analysis and only New York Heart Association class (III or IV) and male gender emerged as significant independent predictors of mortality. Late complications directly related to the composite graft have been gratifyingly low; only 2 patients had coronary dehiscence and 3 had thromboembolic events. Endocarditis emerged as an important late complication in 8 patients (5%). Two patients were successfully treated with antibiotics, 3 died before widespread availability of cryopreserved homografts, and 3 patients treated with antibiotics and homograft root replacement have had no evidence of recurrent infection. Seven patients with dissection in this series had aortic diameters of 6.5 cm or less. This experience supports the concept that composite graft repair in Marfan patients is mandated when the aneurysm reaches 5.5 to 6 cm, even in the asymptomatic patient.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7994091 TI - Management of the severely atherosclerotic aorta during cardiac operations. AB - Embolization of atheroma from the ascending aorta is a major cause of stroke following cardiac surgery. We evaluated a protocol for intraoperative detection and treatment of the severely atherosclerotic ascending aorta which included epiaortic ultrasonographic scanning and resection and graft replacement of the involved segment using hypothermic ischemic arrest. During an 81-month interval, 47 patients 50 years of age and older (mean age 71 years) who underwent coronary artery bypass grafting had resection and graft replacement of the ascending aorta. This represented approximately 2% of the patients in this age group who had cardiac operations during this interval. Nineteen patients (40%) required additional procedures. The 30-day mortality rate was 4.3% (2 patients). Both patients died of myocardial failure. None of the 45 surviving patients sustained a perioperative stroke. There have been no strokes or transient ischemic events in the follow-up period, which extends to 72 months (mean 21 months). While this technique for management of the severely atherosclerotic aorta could be considered radical, it was associated with lower mortality and stroke rates than those that were observed in patients with moderate or severe atherosclerosis in whom only minor modifications in technique were made to avoid embolization of atheroma. Resection and graft replacement during a period of hypothermic circulatory arrest is currently our preferred method of treatment for the severely atherosclerotic aorta during cardiac surgery. PMID- 7994093 TI - Selectivity in aortic root reconstruction. AB - Anatomical variations in aortic root pathology, including combinations of dissection, aneurysmal dilatation, annuloaortic ectasia, and valve disease, defy standardized repair and mandate application of various surgical reconstructions. To examine these techniques, and their influence on morbidity and mortality, we reviewed 53 consecutive patients undergoing aortic root procedures. Thirty-two patients underwent total root reconstruction. Of these, 21 underwent Bentall procedures, 9 had a modification thereof, and 2 underwent a Cabrol reconstruction. Less extensive pathology was corrected in 21 patients with a partial root reconstruction. These included aortic valve replacement (AVR) and a separate tube graft in 14 patients, AVR and primary aortic repair +/- wrapping in 4 individuals, and AVR and patch aortic root enlargement in 3 patients. Mean age was 53.2 years (range 20 to 79). Nearly 20% had undergone previous cardiac surgery and 7.5% were emergencies. Early mortality was 4%. Complications included dysrhythmias (48%), myocardial infarction (4%), stroke (4%), pneumonia (14%), and pancreatitis (2%). There were no reoperations for bleeding. Three late complications, one pseudoaneurysm and two perivalvular leaks, were successfully repaired. Late deaths (13.7%) were caused by congestive heart failure (3), myocardial infarction (MI) (1), cancer (1), stroke (1), and accidental fall (1). Kaplan-Meier analysis reveals 1-, 5-, and 10-year survivals of 98%, 81%, and 66%. Survival and mortality data did not differ between groups, and except for the incidence of atrial dysrhythmias, complication rates also were not significantly different. This series illustrates the need for and the successful application of a selective approach to aortic root reconstruction. PMID- 7994092 TI - Aortic dissection after aortic valve replacement: incidence and consequences for strategy. AB - From 1986 to 1994, 10 patients were observed to have developed an acute aortic dissection at some stage after an aortic valve replacement (AVR). Study of the characteristics of these patients showed that all patients had an aortic diameter of 50 mm or more (range 50 to 80 mm, mean 64 mm), and 70% suffered from systemic hypertension. Subsequently, the echocardiographic database, containing data from 33,105 studies in 21,484 patients, was searched for cases of AVR in which an accurate aortic dimension could be measured. Of 524 patients who had undergone AVR, an accurate aortic diameter was recorded in 419. Thirty-seven patients had an aortic size greater than 50 mm. All acute dissections occurred in this group of patients. The incidence of acute dissections among patients with significant aortic dilatation following AVR was 27%, whereas the overall incidence of acute dissection after AVR is 0.6%. Although there was a preponderance of tilting disc mechanical valves in the dissecting patients, the type of valve implanted does not seem to be of any importance. From these observations, we conclude that implantation of a valved conduit is indicated even in the presence of mild annuloaortic ectasia (aortic size = 50 mm). Patients who have had an AVR and show an enlarging aortic diameter exceeding 50 mm should have an elective reoperation at an early stage, especially when systemic hypertension is present. PMID- 7994094 TI - Diagnosis and therapeutic consequences of intramural aortic hematoma. AB - The classical triad of sudden devastating chest pain, electrocardiographic absence of acute myocardial infarction, and identification of an upstream flap in the ascending aorta by transesophageal echocardiography (TEE) indicates aortic type A dissection requiring emergent surgery. Among 34 patients presenting with clinical signs and symptoms of an aortic dissection, three did not show the mandatory flap in the upstream aorta. The only echocardiographic finding was aortic wall thickening indicating an intramural hematoma. Two of these patients showed early aortic ectasia and one showed a pericardial effusion. Despite the missing flap echocardiographically, surgery was performed in all three patients. The surgical approach was the same as that for patients with a type A dissection. Two patients are doing well after the procedure, and one patient died after reoperation. The postoperative histologic work-up confirmed that there was no intimal tear or dissection of the intimal layer. We conclude that the echocardiographic finding of an intramural hematoma combined with typical clinical signs of chest pain, with myocardial infarction ruled out, requires emergent surgical intervention. PMID- 7994095 TI - Hypothermic circulatory arrest and other methods of cerebral protection during operations on the thoracic aorta. AB - Current surgical techniques in operations on the thoracic aorta frequently require exclusion of the cerebral circulation for varying periods. During these periods, hypothermic circulatory arrest (HCA), selective cerebral perfusion (SCP), and retrograde cerebral perfusion (RCP) can be used for cerebral protection. Hypothermia is the principle component of these methods of protection. The main protective effect of hypothermia is based on reduction of cerebral energy expenditures and largely depends on adequate suppression of cerebral function. It is most effective at deep hypothermic levels (13 degrees C to 15 degrees C). Measures that preserve autoregulation of cerebral blood flow help increase the margin of safety with all methods of protection. There is solid experimental and clinical data indicating the safe limits and outcome following HCA. Current applications of SCP and RCP are fairly recent developments and do not have comparable supporting data. SCP can be used without deep hypothermia and allows prolonged periods of cerebral protection, but is complex in application. RCP is simpler, but always requires deep hypothermia. Present clinical data do not allow separation of its protective effect from that of HCA alone. Recent modifications in the application of HCA include monitoring of cerebral O2 extraction, and selective use of supplemental SCP to limit arrest times to less than 50 minutes, or RCP to prevent embolic strokes, as indicated. These changes appear to have reduced the overall mortality, the severity of embolic strokes, and stroke-related mortality. PMID- 7994096 TI - Tactics and techniques of aortic arch replacement. AB - Operations on the nondissected and dissected aortic arch still pose challenges in terms of the need for and extent of aortic replacement. Our approaches to these lesions are described against the background of 204 operations (58 aneurysms, 54 chronic dissections, and 92 acute dissections), in terms of cerebral protection, procedural choices, and operative technique. Arch anastomoses sparing the supraaortic vessels had shorter periods of circulatory arrest (17.2 min) when compared to tubular arch replacement, with insertion of some or all of these vessels (33.7 min). Early death rates due to cerebral complications were lowest in acute dissections (3/14 fatalities, with two patients showing preoperative cerebral compromise). Based on our experience, we recommend doing subtotal or total arch replacement in aneurysms regardless of cause. Radical arch surgery should be avoided in acute dissections whenever feasible. Instead, the arch should be explored and a blood-tight distal anastomosis made, going beyond any entry tears encountered in that aortic portion. PMID- 7994097 TI - Optimal perfusion pressure for experimental retrograde cerebral perfusion. AB - We evaluated cerebral metabolism during retrograde cerebral perfusion (RCP) and circulatory arrest during profound hypothermia, and also investigated the effects of perfusion pressure on RCP. Twenty-four adult mongrel dogs were placed on cardiopulmonary bypass and cooled to a nasopharyngeal temperature of 20 degrees C. At this temperature, hypothermic circulatory arrest (HCA; n = 6), and RCP with a perfusion pressure of 10 mmHg (RCP10; n = 6), 20 mmHg (RCP20; n = 6), and 30 mmHg (RCP30; n = 6) were carried out for 60 minutes. RCP was performed with oxygenated blood via the bilateral maxillary veins, and the retrograde flow rate was regulated to maintain a mean perfusion pressure of 10, 20, or 30 mmHg in the external jugular vein. At 60 minutes of RCP, we measured nasopharyngeal temperature; regional cerebral blood flow (rCBF); cerebral oxygen consumption, carbon dioxide excretion, and excess lactate; cerebral tissue adenosine triphosphate (ATP), adenosine diphosphate (ADP), adenosine monophosphate (AMP) and energy charge; and cerebral tissue water content. In the RCP10 group, there was excess cerebral lactate, and ATP and energy charge were low. In the RCP30 group, the water content of cerebral tissue was significantly higher than in other groups. In the RCP20 group, temperature was maintained in a narrow range, oxygen consumption and carbon dioxide excretion could be observed, there was no excess lactate, and ATP and energy charge were significantly higher than in the HCA group. In conclusion, RCP can provide adequate metabolic support for the brain during circulatory arrest, and a perfusion pressure of 20 mmHg is most appropriate for RCP. PMID- 7994098 TI - Comparison of retrograde cerebral perfusion to antegrade cerebral perfusion and hypothermic circulatory arrest in a chronic porcine model. AB - Retrograde cerebral perfusion (RCP) is a new method of cerebral protection that has been touted as an improvement over hypothermic circulatory arrest (HCA). However, RCP has been used clinically for durations and at temperatures that are "safe" for HCA alone. This study was designed to compare RCP to HCA and antegrade cerebral perfusion (ACP) deliberately exceeding "safe" limits, in order to determine unequivocally whether RCP provides better cerebral protection than HCA. Four groups of six Yorkshire pigs (20 to 30 kg) were randomly assigned to undergo 90 minutes of RCP, ACP, HCA, or HCA with heads packed in ice (HCA-HP) at an esophageal temperature of 20 degrees C. Arterial, mixed venous and cerebral venous oxygen, glucose and lactate contents; quantitative EEG; were monitored at baseline (37 degrees C); at the end of cooling cardiopulmonary bypass (20 degrees C); during rewarming (30 degrees C); and at two and four hours post intervention. Animals were recovered and were evaluated daily using a quantitative behavioral score (0 to 9). Mean behavioral score was lower in the HCA group than in the other three groups at seven days (HCA 5.8 +/- 1.1; RCP 8.5 +/- 0.2; ACP 9.0 +/- 0.0; HCA-HP 8.5 +/- 0.2, p < 0.05). Recovery of QEEG was better in the ACP group than in all others, but the RCP group had faster EEG recovery than HCA alone, although not better than HCA-HP (HCA 15 +/- 4; RCP 27 +/- 3; ACP 78 +/- 5; HCA-HP 19 +/- 3, p < 0.001). However, histopathological evidence of ischemic injury was present in 5 of 6 HCA animals and also in 4 of 6 of the HCP-HP group, but only in 1 of 6 RCP animals and in none of the ACP group. This study demonstrates that ACP affords the best cerebral protection by all outcome measures, but RCP provides clear improvement compared to HCA. PMID- 7994099 TI - Retrograde cerebral circulation for distal aortic arch surgery through a left thoracotomy. AB - We have devised a simple hypothermic retrograde cerebral circulation technique for protecting the brain during aortic arch surgery. The central venous pressure is simply elevated (15 to 18 mmHg) while the aortic arch is open and the descending aorta occluded, causing oxygen-saturated venous blood from the lower half of the body, which is undergoing deep hypothermic (15 degrees C to 18 degrees C) perfusion, to circulate in the brain in a retrograde fashion, supplying it with oxygen. Twenty-six cases of distal aortic arch aneurysm treated using this method, through a left thoracotomy with femoral vein cannulation, were evaluated. Retrograde cerebral circulation time was 59.6 +/- 13.1 minutes (40 to 93 min). Retrograde flow was 43.9 +/- 13.0 (25 to 62) mL/min. Significant oxygen and apparent lactate extraction were noted in the brain. Early death resulted in 3 of the first 14 cases (21.4%) from embolism, and in 1 of the other 12 cases (8.3%) from massive bleeding and multiple organ failure. Only one late death occurred. No death was attributed to the method itself. This method, with its simplified operative procedure using a lateral thoracotomy, supplied oxygen to the brain and protected it during interruption of the cerebral circulation. Careful management of the atherosclerotic aorta is needed. PMID- 7994100 TI - Protective effect of continuous retrograde cerebral perfusion on the brain during deep hypothermic systemic circulatory arrest. AB - Deep hypothermic circulatory arrest has been widely used as an adjunct for surgery of the aortic arch to protect the brain and other vital organs. We introduced the use of continuous retrograde cerebral perfusion via the superior vena cava during deep hypothermic circulatory arrest in 1987 and have used it in 33 patients. Continuous retrograde cerebral perfusion times ranged from 10 to 89 minutes (mean 40.2 +/- 22.5), and minimal nasopharyngeal temperatures ranged from 14 to 25 degrees C (mean 17.4 +/- 2.0). Two patients with a ruptured aneurysm died during operation due to bleeding and two other patients, with continuous retrograde cerebral perfusion time of 24 and 35 minutes, died 1 month postoperatively due to preoperative liver cirrhosis and sepsis. Two patients suffered from stroke. The remaining 27 patients, including 6 with from 60 to 82 minutes of continuous retrograde cerebral perfusion, had no complications related to continuous retrograde perfusion. During continuous retrograde cerebral perfusion, 66 pairs of blood samples from the perfusate and from the drainage back to the arch vessels were obtained. Analysis of these samples revealed that partial pressure of oxygen, saturation of oxygen, and oxygen content significantly decreased (p < 0.001), and partial pressure of carbon dioxide (CO2) and CO2 content significantly increased (p < 0.001). The nasopharyngeal temperature gradually increased at the rate of 0.01 to 0.03 degree C/min, but was maintained below 20 degrees C. These results reflect the fact that the aerobic metabolism of the brain is maintained during continuous retrograde cerebral perfusion due to oxygen and substrate availability. This technique offers the potential of metabolic support to the brain during deep hypothermic circulatory arrest and prolongs the safe time limits of deep hypothermic circulatory arrest in surgery of the aortic arch. PMID- 7994101 TI - The use of somatosensory evoked potentials to determine the optimal degree of hypothermia during circulatory arrest. AB - We sequentially recorded subcortical (P14) and cortical (N20) somatosensory evoked potentials (SEPs) in 32 patients undergoing deep hypothermic circulatory arrest (CA). Under normal hemodynamic conditions, hypothermia initially produced N20 disappearance at a mean nasopharyngeal temperature of 20.4 +/- 2.6 degrees C (range 14.5 to 26.1 degrees C) and P14 disappearance at a mean of 16.9 +/- 2.0 degrees C (range 12.4 to 20.2 degrees C). On rewarming, P14 reappeared at mean temperature of 19.3 +/- 4.0 degrees C (range 13.5 to 29.2 degrees C) and N20 at a mean of 21.1 +/- 4.1 degrees C (range 14.3 to 29.6 degrees C). The delay of SEP reappearance after restoration of blood flow correlated significantly with CA duration (r = 0.74 for P14, and r = 0.62 for N20; p < 0.01). Neurological recovery was uneventful in 23 patients; 5 patients presented with neurological sequelae (minor or transient in 4; no recovery from anesthesia and death after 48 hours in 1), and 4 patients died during operation. Twenty-three of 24 surviving patients in whom P14 disappearance was the criterion that hypothermia was deep enough to perform CA (duration: 17 to 94 min) had a normal neurological outcome. By contrast, all surviving patients in whom cortical SEPs disappeared at higher temperatures presented neurological sequelae. In conclusion, the neurophysiological monitoring of brain stem activity, as specifically provided by SEPs, enables determination of the optimal temperature for CA, and demonstrates superiority of SEP monitoring over the use of EEG. PMID- 7994103 TI - Molecular ecology and evolution: approaches and applications. PMID- 7994102 TI - One-stage intrathoracic repair of extended aortic aneurysms. AB - Aneurysms of the entire thoracic aorta are usually approached in two to three stages. From 1990 to 1994, we performed one-stage aortic replacement from the root to the diaphragm in 16 patients (8 men and 8 women with a mean age of 55.7 years, range 49 to 73). There were 11 type A dissections, 7 of which were acute. Six patients underwent aortic valve reconstruction; seven had aortic root replacement by Bentall or Cabrol techniques. In two cases, the innominate artery had to be replaced by a vascular graft separately in addition to reimplantation of the supraaortic branches as an island flap into the arch prosthesis. In eight cases, a median sternotomy was used; eight had a bilateral transverse thoracotomy. The procedure was performed under deep hypothermic circulatory arrest in all cases (mean duration 50.5 min, range 38 to 62 min). Two patients, both operated upon for an acute dissection, expired perioperatively: one due to a bronchopneumonia, and one because of a thrombosed Cabrol graft to the right coronary artery. No patient developed bleeding or neurological complications. At a mean follow-up of 26.9 months (1 to 50 months), all patients discharged from the hospital were still alive. Four patients underwent subsequent thoracoabdominal aortic replacement. This experience suggests that complete thoracic aortic replacement can be performed in a single session with an operative risk comparable to that of the conventional two-stage approach. The bilateral transverse thoracotomy affords excellent exposure. The lack of spinal cord ischemia may be the result of spinal cord protection with hypothermic circulatory arrest and use of the open-clamp technique. PMID- 7994104 TI - Molecular techniques in population genetics: a brief history. PMID- 7994105 TI - Organization of genetic variation at the molecular level: lessons from Drosophila. PMID- 7994107 TI - The use of microsatellites for genetic analysis of natural populations. AB - Microsatellites, tandemly repeated units of 2 to 5 bp are distributed throughout eukaryotic genomes. Length variation within microsatellites, caused by DNA slippage, can be amplified by PCR and used for DNA profiling. In this paper potential applications and limitations of this technique are discussed. Two case studies for pilot whales (Globicephala melas) and sheep (Ovis aries) exemplify the suitability of microsatellites for analyzing natural populations. Other currently available profiling techniques are compared to microsatellite analysis. PMID- 7994106 TI - The use of microsatellite analysis in population biology: background, methods and potential applications. AB - A promising technique currently emerging for population studies is the analysis of microsatellite DNAs. Microsatellite alleles offer several advantages over other types of molecular markers. They are abundant, highly variable, and can be assayed from minute quantities of DNA using PCR. Their major disadvantage is that it is usually necessary to screen genomic libraries to identify and characterize microsatellite loci for each species under investigation. The first goal of this chapter is to summarize background information having implications for population studies. This information comes primarily from human genome literature and is therefore not easily accessible to many population biologists. Secondly, because microsatellite analysis uses molecular approaches that are new to most population biologists, we attempt to provide a rationale and overview of methodology. Finally, we review population studies to date that have used microsatellite analysis and offer our perspective on the potential for future studies. PMID- 7994108 TI - PCR assays of variable nucleotide sites for identification of conservation units. AB - A number of authors have recently suggested that the best approach for identifying units of conservation is to follow a systematics model of character analysis (Amato, 1991; Cracraft, 1991; Vogler and DeSalle, 1994). This approach necessitates the use of an operational, typological, evolutionary species concept. The use of the phylogenetic species concept has the utility and philosophical logic appropriate for this task. Additionally, there is a large body of literature that uses this framework, along with a parsimony based character analysis to identify patterns of phylogeny (Cracraft, 1983; Nelson and Platnick, 1981; Nixon and Wheeler, 1990). While we advocate this approach, we recognize that one of its limiting factors is sample size. We propose that by selective direct sequencing plus rapid sampling of variable target characters by polymerase chain reaction (PCR) assays of specific sites, sufficiently large numbers of individuals can be accurately, inexpensively, and quickly surveyed for diagnostic characters. This procedure is demonstrated by a survey of variable nucleotide sites in the Caiman crocodilus complex. PMID- 7994110 TI - Advances in the theory and practice of DNA-hybridization as a systematic method. AB - DNA hybridization continues in the 1990s to provide insight into phylogeny and evolution. The resilience of this 30-year-old distance technique may be attributed to its fundamental power as a comparative method, as well as to advances in our understanding of its operation and improvements in experimental design and data analysis. These attributes and advances, along with the assumptions and limitations of DNA hybridization, are discussed in this paper. Examples are provided of recent DNA hybridization studies of molecular, morphological, and behavioral systematics and evolution. PMID- 7994109 TI - Concerted evolution and RAPping in mitochondrial VNTRs and the molecular geography of cricket populations. AB - In recent years, many animal species have been shown to exhibit a variable number of tandem repeats (VNTR) in the control region of their mitochondrial DNA. To characterize the nucleotide polymorphism of a VNTR system, this region was sequenced in individuals from two species of crickets (genus Gryllus) collected at a mainland locality and an island locality within each species. The data reveal a clear pattern of concerted evolution: homogeneity among repeats within individuals and populations, but heterogeneity among the tandem arrays from divergent populations, and between species. The patterns of nucleotide polymorphisms within the arrays show several instances of partial homogenization where derived nucleotides have not swept through all the repeats in the array. These serve as examples of concerted evolution "caught in the act". Additional repeat associated polymorphisms (RAPs) shed light on the molecular basis of the insertion and deletion of repeat units and, with the concerted evolution of VNTRs, provide phylogeographic resolution of island and mainland populations within and between species. The polymorphisms within VNTRs also provide a simple system in which to examine the balance of mutation and drift and offer a unique view of the histories of genomic and organismal phenomena in the patterns and processes of molecular evolution. PMID- 7994112 TI - Analysis of DNA from natural history museum collections. AB - Genetic data derived from museum collections have an important role in systematics, conservation biology, ecology and medicine. Technical advances in molecular biology are increasing the range of material in collections amenable to such analysis. While the very diversity of natural history collections sometimes makes generalisations difficult, classes of extraction procedures and precautions against contamination can be described. Destructive sampling of specimens for genetic studies raises a number of institutional issues, such as granting of permission to use particular specimens and the return of DNA to the museum housing the specimens. Molecular biology is seen as further enhancing the value of collections. PMID- 7994111 TI - Allozymes in mammalian population genetics and systematics: indicative function of a marker system reconsidered. AB - Data from an extensive research project on lagomorphs were compiled and re analyzed from a synoptical point of view for examining the indicative function of allozymic variation. Empirical data suggested the Shannon-Weaver information index to be a better indicator of allelic diversity than expected average heterozygosity. There were differences in polymorphism among various structural and physiological classes of enzymes. Reliable estimates of gene diversity and genetic distances can be obtained only if more than 30 loci are examined. At the population level, allozymic diversity was not related to morphological variation. It was, however, indicative of increased developmental homeostasis as assessed by overall fluctuating asymmetry in non-metric morphological traits. Allozymes served well for fully resolving genetic differentiation among populations and for assessing levels of migration, whereas mtDNA and morphological data provided only additional information. The results are discussed with respect to data from other mammalian taxa. PMID- 7994113 TI - Sources of ambiguity in nucleic acid sequence alignment. AB - The discussion of molecular sequence alignment is becoming more prominent in studies of molecular systematics and evolution. As the basis for initial homology statements, alignment is crucial to comparative molecular biology. Although fundamental, alignment is not a process which necessarily yields objective, precise results. Ambiguities can appear in alignment due to a number of factors. Three such sources of ambiguity are discussed here. These are ambiguity in the establishment of alignment parameters, pair-wise order and individual "path" variation. The first arises from the necessary but empirically untestable assumptions of gap costs and other factors which are required to align sequences objectively. The second is due to the possible existence of non-unique solutions to the same alignment parameters in heuristic and exact solutions. The third is a result of multiple optimal paths within single alignments, potentially generating huge numbers of equally costly but unique alignments. Some of the problems with and several possible solutions to the difficult situation of non-unique alignments are discussed. PMID- 7994114 TI - The analysis of simple repeat loci as applied in evolutionary and behavioral sciences. AB - This chapter describes several aspects of tandemly organized, simple repetitive DNA sequences and their usefulness for genetic relationship analyses. After introducing the structure, the evolution and the biological meaning of such target sequences in a particularly well-studied gene, we discuss oligonucleotide probes for generating individual specific multilocus banding patterns. Thus, oligonucleotide fingerprinting allows to approach novel problems in behavioral sciences. Here, we use a passerine bird, the great tit (Parus major) as an example. Finally, genomic fingerprinting is compared to sensitive amplification methods requiring less DNA. Advantages and shortcomings of these techniques need to be evaluated in the context of the biological question(s) asked and, above all, the quality and quantity of the starting material. PMID- 7994115 TI - Computational problems in molecular systematics. AB - The development of extremely powerful computer programs and the ready availability of microcomputers has revealed several computational problems with data analysis. These problems occur in the handling of systematic data in general and molecular systematic data in particular. This paper examines three areas of controversy in molecular systematics resulting from increased computer power. We start by examining the first step in DNA sequence analysis, the establishment of homology via sequence alignment. Next we examine several problems in phylogenetic analysis that have arisen in the last few years due to use of the PAUP (Swofford, 1991), HENNIG86 (Farris, 1988), and PHYLIP programs. These problems include limitations on the number of taxa examined in a given analysis and the accuracy of the parsimony trees in such analyses. The final subject is an examination of programs used for assessing tree robustness. We concentrate on certain programs (such as MALIGN (Wheeler and Gladstein, 1993), PAUP (Swofford, 1991), HENNIG86 (Farris, 1988), PHYLIP (Felsenstein, 1990), CLADOS (Nixon, 1993), MacClade (Maddison and Maddison, 1993), etc.), but similar comments about other programs could also be made. PMID- 7994116 TI - The comparison of morphological and molecular data in phylogenetic systematics. AB - Analytical methods facilitating the use of molecular and morphological characters as complementary sources of phylogenetic information are explored. Separation of phylogenetically useful information from misleading patterns of character variation is most effective when the methods of "taxonomic congruence" and "character congruence" are used together. Statistical approaches for implementing both methods are described and illustrated with an example from the phylogeny of salamanders. PMID- 7994117 TI - Non-coding chloroplast DNA for plant molecular systematics at the infrageneric level. AB - With primers constructed against highly conserved regions of tRNA genes (trnTUGU, trnLUAA and trnFGAA) in chloroplast DNA, we have amplified two different non coding spacers and one intron from four species within the genus Echium L. (Boraginaceae) and from two confamilial outgroups. The trnTUGU-trnLUAA intergenic spacer contains a greater number of polymorphic sites than the trnLUAA intron or the trnLUAA-trnFGAA intergenic spacer. We analyzed a total of 11 kb of sequence data from this non-coding DNA. Total nucleotide divergence between Echium species is on the order of 1% for these regions, all of which possess infrageneric length polymorphisms. The latter two regions contain indels which occur only in the 14 Macaronesian Island endemic species of Echium studied and suggest that these may form a monophyletic group. PMID- 7994118 TI - Multilocus DNA fingerprinting and genetic relatedness in plants: a case study with banana and tomato. AB - The technique of DNA fingerprinting is frequently used for studies of genetic diversity and relatedness in a wide range of organisms. In humans and animals, multilocus fingerprints are mainly applied to paternity and identity test cases, behavioral ecology, and the analysis of population structures. In plants and fungi, the frequent occurrence of "low-variability" fingerprint patterns additionally allows to use multilocus fingerprinting for studying taxonomical problems at an intraspecific level. In the present article, we (1) present an overview of such approaches in a series of plant species, (2) summarize our attempts to estimate genetic relationships within two cultivated plant species, banana and tomato, by band sharing data derived from oligonucleotide fingerprints, and (3) discuss the limitations and potentials of multilocus fingerprinting for the determination of genetic relatedness. PMID- 7994119 TI - The role of molecular genetics in speciation studies. AB - Systematists and population geneticists can both use molecular data sets to construct evolutionary trees (species and gene trees, respectively), and then use the resulting historical framework to test a variety of hypotheses. The greatest prospect for future advances in our understanding of speciation is to extend these historical approaches to the species/population interface, for only by straddling this interface can we actually study the processes involved in the origin of a new species. This chapter illustrates how the bottom-up historical approaches used in population genetics can be extended upwards to this critical interface in order to separate the effects of population structure from population history, to rigorously test the species status of a group, and to test hypotheses about the process of speciation by using gene trees to define a nested, statistical analysis of biogeographic and other types of data. PMID- 7994120 TI - The origin and evolution of species differences in Escherichia coli and Salmonella typhimurium. AB - Since diverging from a common ancestor some 120 million years, Escherichia coli and Salmonella typhimurium have accumulated numerous phenotypic characteristics which have traditionally been used to distinguish these enteric species. While most of the genetic differences between these species are due to the accumulation of point mutations, the majority of the observed variation in phenotypic characters is attributable to segments of the genome confined to only one of the species. We have analyzed the map positions, G+C contents, nucleotide sequences and functions of regions unique to the Salmonella chromosome in an attempt to determine the ancestry of species-specific sequences. Some of the Salmonella specific regions had uncharacteristically low base compositions and contained open reading frames of atypical codon usage patterns suggesting that portions of the genome were acquired by horizontal transfer from distantly-related bacterial species. The role of these species-specific sequences was assayed by constructing mutant strains harboring deletions in the corresponding regions of the genome. Several functions were ascribed to these unique portions of the Salmonella chromosome, including one encoding proteins involved in virulence and invasion of host epithelial cells. PMID- 7994121 TI - The evolutionary ecology of Daphnia. AB - In order to generate genetic markers from both nuclear and mitochondrial DNA, we used three PCR-based techniques (RAPD, mtDNA-RFLPs, and sequencing of an amplified mtDNA fragment) to illuminate various aspects of the population genetics of large-lake Daphnia species. Estimations of genetic diversity at different taxonomic levels integrated with ecological data revealed insights into the genetic components of the evolutionary process of interspecific hybridization in these Daphnia species, which had previously been documented with allozyme markers. Our new molecular data suggest the occurrence of recent hybridization and backcrossing events, and allow the identification of the maternal species of hybrid clones. PMID- 7994123 TI - Evolutionary analysis of genes involved in early embryonic pattern formation in Drosophila. AB - Segmentation and homeotic genes have originally been identified and analyzed in Drosophila. Molecular techniques such as low stringency hybridization or PCR now allow to clone homologs of these genes from different organisms. This provides a basis to study the evolution of pattern formation mechanisms between organisms at the gene level, creating a new discipline: molecular comparative embryology. This chapter discusses the practical and conceptual problems arising from this approach. PMID- 7994122 TI - Diversity within diversity: molecular approaches to studying microbial interactions with insects. AB - DNA sequence information has greatly augmented the number of characters available for analysis in phylogenetic research. Nowhere is this more evident than in studies of microbial evolution. Ribosomal DNA sequence data has simultaneously permitted the distinction between individual species and the inference of their phylogenetic relationships in many cases where both were formerly impossible. These have contributed to our understanding of the ecology of particular microbe host interactions and the history of these relationships over evolutionary time. We describe examples from two ends of the ecological spectrum in insect/bacterial associations: one in which bacteria mediate host cytoplasmic incompatibility and parthenogenesis, and the other in which mycetocyte bacteria augment host nutrition. In the former, the pattern of bacterial interaction is general, with the same or closely related strains of the genus Wolbachia associating with a wide range of insect taxa. In the latter, concordance between host and microbe phylogenies suggests cospeciation between bacteria and host, although it is as yet unclear whether this process has involved step-wise, reciprocal coevolution. We conclude with a discussion of how developments in molecular techniques may aid in analyzing more complex interactions between insects and microbes. PMID- 7994124 TI - Evolution and multi-functionality of the chitin system. AB - Chitin, that is, the beta-1, 4 linked polysaccharide of N-acetylglucosamine, is best known as a cell wall component of fungi and as skeletal material of invertebrates. In recent years this simple picture has changed dramatically. Three developments have taken place: the discovery of chitinous tissues in vertebrates, the molecular analysis of the chitin-synthase genes, and the discovery that chitin derivatives play a crucial role in the interaction between higher plants and symbiotic bacteria. In this paper the methods for chitin detection and the current data on the evolution of chitin synthesis are reviewed. In addition, data is summarized which suggest that chitin synthesis may serve roles other than the production of skeletal material. In particular, anecdotal evidence suggests that chitin derivatives may play a role as signals in plant as well as animal development. Two major unresolved questions are identified: 1) Is there historical continuity of all the chitin synthesizing systems in protists, animals and, in particular, the deuterostome animals. 2) Are chitin derivatives actually involved in the development of plants and animals? PMID- 7994125 TI - Genome evolution: between the nucleosome and the chromosome. AB - Intermediate between DNA sequences and broad patterns of karyotypic change there is a major gap in understanding genome structure and evolution. The gap is at the megabase level between genes and chromosomes. New methods for analyzing large DNA fragments cloned in yeast or bacterial vectors provide experimental access to genome evolution at the megabase level by enabling the assembly of megabase-size contiguous regions. Genome evolution at the megabase level can also be studied using high-resolution genetic maps. Rates and patterns of genome evolution in mammals (mouse versus humans) and Drosophila (D. virilis versus D. melanogaster) are compared and contrasted. Opportunities for research in genome evolution using the new technologies are enumerated and discussed. PMID- 7994127 TI - Perspectives on future applications of experimental biology to evolution. AB - The first three decades of the subdiscipline of biology known as "molecular evolution" have generated large amounts of new information that illuminate the nature of evolutionary pattern and process. Major progress has been made in identifying primary sequence variation in genes and their protein products, initially from biochemically tractable systems (from large or culturable organisms and from highly-reiterated genes or highly-expressed gene products). In the 1980s, these techniques that had been limited to specialists, to relatively few representatives of the diversity of life, and to a small number of those organisms' genes, were extended through advances in molecular genetics and biochemistry, resulting in an explosion of molecular information and a proliferation of molecular trees. Studies of variation in molecular characters also were rarely linked with studies of anatomical, behavioral or ecological diversity. More sophisticated molecular genetic and biochemical techniques, currently being applied to long-standing questions in cell and developmental biology in model systems, should be applicable to more diverse lineages in the next decade. Molecular trees produced from one or more "housekeeping genes" can identify key lineages (species, populations, genomes or gene families) which, by comparison to model systems, may illuminate important aspects of higher level variability. Thus, the next phase of research in the field of molecular evolution should see greater linkage between studies of simple molecular and more complex developmental characters, and increased functional testing of genes and gene products in an evolutionary context. This review highlights some comparative experimental approaches that I believe will be most effective in extending our understanding of molecular evolution and better linking the field to other areas of science in the next few years. PMID- 7994126 TI - Individual genes underlying quantitative traits: molecular and analytical methods. AB - Because of innovations in quantitative and molecular genetics, it is becoming possible to study the individual loci affecting quantitative traits, quantitative trait loci (QTL). We review a number of recently developed molecular and analytical techniques that allow the identification and localization of QTL and the quantification of their effects, and present an example. We suggest that this area of investigation, already in widespread use in the agricultural and medical sciences, will become increasingly important in evolutionary biology as techniques continue to improve. PMID- 7994129 TI - Why Sister Cooksley had to go. PMID- 7994128 TI - Unravelling the components that underlie insect reproductive traits using a simple molecular approach. AB - Applications of RAPD technology to questions of paternity and maternity in studies of insect reproductive traits are discussed. We present three case studies where RAPD fingerprinting reveals levels of complexity in insect systems that help us to understand the causal mechanisms underlying observed behaviour. Finally, we consider ways in which RAPD data can be analysed to generate information about kinship. PMID- 7994130 TI - Getting our act together for the severely mentally ill. PMID- 7994131 TI - Role of nurses in antibiotic therapy. PMID- 7994132 TI - Drugs used to control asthma. AB - The diagnosis of asthma is only the beginning of asthma care. Every patient is an individual and asthma care must be tailored to the patient. The aim is to control the symptoms of asthma with the minimum of drugs, a suitable delivery system and minimal interruption of everyday life. PMID- 7994133 TI - Diabetic ketoacidosis. PMID- 7994134 TI - Blood and urine tests for diagnosis and monitoring of diabetes. AB - The diagnosis of diabetes is made on the evidence of raised blood glucose levels. In diabetic patients, regular monitoring of blood and urine guides decisions about treatment and helps to minimise the risk of complications. This article describes various diagnostic tests that can be used both in the laboratory and outside. PMID- 7994135 TI - Diabetes in childhood. AB - Insulin-dependent diabetes mellitus is the most common endocrine disorder of childhood. Early diagnosis is important. A multidisciplinary team approach enables families to assume responsibility for self-management. The paediatric diabetes nurse specialist is a key member of the team. PMID- 7994136 TI - Reducing the incidence of sharps injuries. AB - Sharps injuries are the primary route through which health care workers acquire blood-borne diseases occupationally (Lynch et al, 1992). In order to reduce the incidence of such injuries effectively within a hospital, it is vital to first ascertain the frequency and types of injuries and then implement a risk-reduction programme based on the specific problems identified. PMID- 7994137 TI - Should we listen to gossip? PMID- 7994138 TI - Hollister impression. AB - Despite modern surgical techniques, stomas continue to produce practical management problems for some individuals. This product focus appraises the use of Hollister Impression, an appliance with built-in convexity, designed to reduce or remove the problem of leaks for the ostomist. PMID- 7994139 TI - Ethnic Irish older people. AB - Older Irish people experience considerable ill health and social deprivation. The absence of a specific Irish ethnicity category from official statistics has led to a failure to identify the needs of this large and elderly population. PMID- 7994140 TI - Labour opposes performance-related pay. PMID- 7994141 TI - Who should be giving nurses professional advice? PMID- 7994142 TI - UKCC's response to the Sister Cooksley case. PMID- 7994143 TI - Pressure area risk assessment in a neurological setting. AB - Hospital-acquired pressure sores are a costly and often avoidable drain on both patient and hospital resources. This article describes the process and rationale behind a multidisciplinary attempt to develop an effective risk assessment tool for use in a specialist neurosciences setting. PMID- 7994145 TI - Profiling and nursing practice. AB - This article examines profiling, with particular reference to profiling approaches and the use of profiling in preregistration nursing. It also identifies some of the difficulties that have arisen in relation to diary keeping and the use of a competence approach to education. It is taken from and forms part of a working paper produced for West Midland Regional Health Authority on profiles and accreditation of prior experiential learning. PMID- 7994144 TI - Containing incontinence in men: an extra dimension. AB - The prevalence and nature of incontinence means that all nurses will see patients who suffer from this condition. Many professionals remain unaware of products that can assist in the management of such patients. This article describes experience with some of the products available, highlighting their clinical usefulness and effectiveness. PMID- 7994146 TI - Teaching research methods to nursing students. AB - This article addresses the teaching of research methods to student nurses. An eclectic approach is advocated within which traditional, experiential and action oriented methods are used. This approach is illustrated by means of an example in which it was used to help students understand the analysis of qualitative data. Suggestions regarding the integration of research within nursing courses are also given. PMID- 7994147 TI - Academic credit and professional experience. AB - Accreditation of experiential learning is being promoted as a legitimate cost effective method of short-cutting professional degree courses for qualified practitioners. While there are benefits in giving academic recognition for learning gained from experience, there is a danger that the pressure of market forces may devalue the status of nursing degrees. PMID- 7994148 TI - A career in cancer nursing. AB - Cancer nursing offers much to the professional nurse and is a popular and rewarding career choice. It remains, however, a demanding role and one that should not be chosen without careful consideration of what is involved. PMID- 7994149 TI - Mental illness: diagnosis or value judgment? AB - This article is concerned with the definition of mental illness. Although it seems that it cannot be defined clearly in a legal or scientific way, this does not necessarily mean that health treatment is arbitrary and ill-founded. PMID- 7994150 TI - Use of the Baxter PCA infusor in the community. AB - This article gives an account of the care given to a terminally ill patient who wished to remain at home and in complete control of her symptoms using equipment and techniques usually reserved for hospital in-patients. PMID- 7994151 TI - Role of the UKCC's Preliminary Proceedings Committee. PMID- 7994152 TI - Kaltostat. AB - The wound dressings in C V Laboratories' Kaltostat range are composed of calcium sodium alginate. By managing the physical aspects of wounds, they also reduce the associated psychological distress. PMID- 7994153 TI - The health of traveller-Gypsies. AB - Travellers are not a healthy group. They experience widespread prejudice and discrimination from the settled population. In the sphere of health care, they have poor access to services. This article reviews the prevalent health care needs of this group from the perspective of client factors and service factors. PMID- 7994154 TI - "Hanseniaspora uvarum" the ultrastructural morphology of a rare ascomycete, isolated from oral thrush. AB - Superficial fungal infections, including oral thrush, often affect aged full denture wearers and many individuals over 65 years old. The aim of this study was to examine the ultrastructural morphology of a very rare yeast, named Hanseniaspora uvarum/guillermondi, member of the Ascomycetes family, whose pathogenesis and behaviour is not widely known. The yeast was isolated from whitish lesions of the buccal mucosa of an 70 years old woman. The specimen was collected with a mouth swab and cultured in Sabourauds-Dextrose agar. The identification of the organism was performed on the Api 20C Aux system. The yeast colonies, after fixation in glutaraldehyde 3% for 1 hour were immersed in OsO4 1% solution for 1 hour and were "in tissue" stained with uranyl acetate. Ultrathin sections, were observed with TEM Jeol C x 100. Our ultrastructural observations showed that this yeast had a thick cell wall in which the outer surface appeared fuzzy. In some yeasts we observed multilayered intracytoplasmic membrane a figure which is not described as far as we know in any yeast. Many vacuoles were frequently observed in the cytoplasm and especially in the center of the oval shaped cells. Bilateral budding which form ascospores is identical for the morphology of this yeast. PMID- 7994155 TI - [The use of computer-assisted stabilometry in the diagnosis of craniomandibular disorders]. AB - The aim of this study was to evaluate the influence of the cervical region and the stomatognathic system on the balance control. We examined 35 healthy subjects and 201 balance disorder patients; of the 201 patients 60 suffered also from craniomandibular disorders (CMD) and 40 from cervical rachis disease. All cases were tested by computerized stabilometry executed in Romberg position: with closed eyes, retroflexed head and two cotton roles between the dental arches. The results show that cervical rachis disease and stomatognathic dysfunction have a significative influence on the balance control; however, this influence is smaller than that of vestibular disease; moreover, the computer stabilometry allows to measure the degree of ascending or descending correlation between the posture and stomatognathic system. PMID- 7994157 TI - Ultrastructural analysis of periapical granulomas. AB - A large portion of periapical granulomas is composed by cells of the mononuclear phagocyte and lymphoid system. The ultrastructural features of the monocytes/macrophages differ in relationship to the state of activity of the cells (phagocytosis or secretion). A close correlation between cells of these two systems can be surmised by their tight contacts. An important role in the bone resorption is probably played by cytokines like IL-1 and TNF. PMID- 7994156 TI - [The role of stabilometry in assessing the correlations between craniomandibular disorders and equilibrium disorders]. AB - We examined three groups: 29 patients suffering from balance disorders and craniomandibular disorders but from vestibular disease; 21 patients suffering from balance disorders, craniomandibular disorders and vestibular disease; 26 patients suffering from craniomandibular disorders but not from vestibular disease or balance disorders. All cases were examined by the odontologist and otoneurologist and tested by computerized stabilometry; they were reexamined after six months of therapy by an occlusal stabilization splint. The static analysis of the results show a significative reduction of the postural oscillations in all patients. PMID- 7994158 TI - Anti-DNA antibodies and circulating immune complexes (C1q-IgG) in recurrent aphtous stomatitis. AB - Anti-DNA antibodies and circulating immune complexes (C1q-IgG) in sera from 50 patients with minor aphtae at the moment of study and 50 healthy controls, were determined. The obtained results were correlated with chronological and clinical parameters of the disease. Our findings show a greater number of patients than controls with higher values of anti-DNA antibodies. The time from the last active stage of the disease conditioned the anti-DNA antibody levels (p < 0.001). However, no significant differences among the number of recurrences in a year or the number of lesions in a ulcerative stage and the anti-DNA antibody concentrations were observed. PMID- 7994159 TI - [The pterygoclival trihedron: its 3D reconstruction, stability and possible variations during growth]. AB - The growth's study, from skull's radiographics, needs the use of superposition's structures. Three X-ray radiographics pictures from the front, from profile and from under are retalling by a soft. This orthogonalization's step has been realized for every child at two different ages. The reconstruction of the "clivus" straight and "pterygoide" straights from three views gives the "pterygo clivus triedre" which stability is studied for time. PMID- 7994160 TI - Oral lichen planus. An evolutive clinical and histological study of 45 patients followed up on for five years. AB - A study is made of 45 patients clinically and histologically diagnosed of oral lichen planus, and followed up on for 5 years. The course of the disease was monitored after three months and one, two and five years. The patients were classified in terms of lesion evolution (healed, improved, stationary or worse). Two evolutive groups were established for statistical purposes: (a) favorable (healed or improved lesions) and unfavorable cases (stationary or worsened oral lesions); and (b) healed and non-healed cases. Statistical correlations were established between these evolutive groups and different clinical and histological parameters, in an attempt to identify parameters of predictive value in the course of the disease. No statistically significant results were obtained, with the exception of inflammatory infiltrate. Thus, the depth of this infiltrate was found to be greater in patients with an unfavorable evolution (p = 0.02) than in those with a favorable course. Likewise, the inflammatory infiltrate was greater in non-healed than in healed cases. PMID- 7994161 TI - [The value of the CO2 laser for bonding composite resins to dentin]. AB - CO2 laser irradiation brings about structural modifications at the dentin surface. The aim of this study was to compare the tensile strength of composite resin bonded to unlased dentin and lased dentin. Dentin specimens were prepared by vestibular surface sectioning, exposing a plane dentinal surface. 40 specimens received 20 individual laser impacts with a power of 4 W and a duration of 0.1 s. 20 specimens received no laser irradiation. Half of the 60 specimens was treated with Scotchbond 2 and the other one with Scotchbond Multipurpose. Composite cylinders were polymerised for 40 seconds to these specimens. Tensile bond strengths were determined at a crosshead speed of 5 mm/min and fractured surfaces were examined at SEM after the test. Unlased dentin had significantly higher bond strength that the lased dentin. PMID- 7994162 TI - Organ-localized hypothalamic-stimulated vasculature changes in the cat. AB - Stimulation of specific lateral hypothalamic targets in a cat model induces vascular and/or cardiac changes. Evidence is presented that these may consist of discretely localized sympathetically mediated changes taking place in just one or two organs. Moreover, following stimulation of either one of two adjacent lateral hypothalamus sites, pressor effects are induced that superficially look similar, but prove to be mediated by different pathways. To investigate possible synapsing at sympathetic ganglia, e.g. in superior cervical or stellate ganglia, 50 micrograms atropine methyl nitrate, a ganglionic blocker, was applied directly to the ganglia. This was shown to potentiate the pressor effects, in some cases when applied to the superior cervical ganglia, in others to stellate ganglia, presumably by blockade of a ganglionic attenuating mechanism. The contributions made by different sympathetic nerves to the lateral hypothalamus-induced pressor effect were analysed. Stimulation of one of the lateral hypothalamus sites (TAR.I) in eight cats induced a pressor effect that was abolished by severing a nerve branch, from the superior cervical ganglia laterally, shown to innervate neck muscle vasculature. In another group of nine cats stimulation of TAR.II induced a pressor effect abolished by cutting a branch from the superior cervical ganglia medially, shown to be destined to the vasculature of pharyngeal muscles and possibly lower respiratory tract. The hypothesis that central control via the sympathetic nervous system is responsible for differential organ specific regulation of blood flow to individual organs is discussed. PMID- 7994163 TI - Plasma neuropeptide Y in the symptomatic limb of patients with causalgic pain. AB - The aim of this experiment was to measure the concentration of neuropeptide Y (NPY), a vasoactive transmitter which co-exists with noradrenaline in sympathetic nerve terminals, in venous blood taken from the painful and contralateral limbs of 16 patients with features of reflex sympathetic dystrophy (RSD) or causalgia. In nine patients tapping the skin of the affected limb provoked pain (allodynia). In seven of the nine patients with allodynia the concentration of NPY was lower on the painful side; similar results were obtained in only two of seven patients without widespread allodynia. In addition, the concentration of NPY was generally lower in the painful limb if it was warmer than the contralateral limb. These findings suggest that a reduction in sympathetic activity might accompany allodynia and influence vasomotor disturbances in patients with causalgic pain. PMID- 7994164 TI - Investigation of parasympathetic and sympathetic cardiac innervation in diabetic neuropathy: heart rate variation versus meta-iodo-benzylguanidine measured by single photon emission computed tomography. AB - In diabetic neuropathy disturbed autonomic cardiac innervation is associated with shortened life expectancy. Sympathetic dysfunction is likely to play a role in cases of cardiac death. The quantitative uptake of the radiopharmaceutical iodine 123-meta-iodo-benzylguanidine (MIBG) can be measured by single photon emission computed tomography (SPECT). It is an index of the functional integrity of sympathetic neurones in the heart. The respiratory heart rate variation--as assessed by a computerized device--reflects mainly parasympathetic cardiac innervation. In 25 diabetic patients and 19 healthy subjects MIBG-SPECT and heart rate variation tests were carried out. MIBG scans in all normal subjects showed homogeneous uptake of activity. In 12 out of 25 patients at least two heart rate variation tests were abnormal. MIBG-SPECT was more sensitive (abnormal in 17 out of 25). The lack of correlation between MIBG-SPECT results and spectral analysis of heart rate variation suggest that spectral analysis alone should not be regarded as an indicator of sympathetic cardiac innervation. PMID- 7994165 TI - Vasodepressor reactions after orthotopic cardiac transplantation: relationship to reinnervation status. AB - Ventricular vagal nerve endings are thought to trigger vasodepressor syncope. Reports of vasodepressor reactions associated with donor bradycardia after cardiac transplantation have led to speculation that vagal reinnervation occurs. We assessed reinnervation status in seven patients 23-36 months (median 24 months) post-transplantation. Heart rate responses to vagal manoeuvres (respiration, Valsalva) and sympathetic stimuli (exercise and injection of tyramine into the coronary artery supplying the sinus node) were measured. All patients underwent 60 min of 60 degrees head-up tilt with foot plate support. During tilt four of the seven had vasodepressor reactions with a fall in mean arterial pressure of 20-90 mmHg. During vasodepression two patients had falls in donor heart rate of 13 and 40% relative to peak heart rate during tilt. These two patients had evidence of functional sympathetic reinnervation. By contrast the two patients without donor bradycardia during vasodepression had only limited or no evidence of sympathetic reinnervation. No patient had consistent evidence of parasympathetic reinnervation as judged by the heart rate response to vagal manoeuvres. Head-up tilt can thus produce vasodepressor reactions with donor bradycardia after cardiac transplantation in the absence of consistent evidence of vagal reinnervation. Left ventricular nerve endings may not be the only mediators of tilt-induced vasodepressor reactions in man. Donor bradycardia during vasodepression may reflect sympathetic withdrawal and not vagal reinnervation. PMID- 7994166 TI - Metabolic heat production and cardiovascular responses to an incremental intravenous infusion of adrenaline in healthy subjects. AB - Increased circulating adrenaline causes a rise in metabolic heat production and well characterized cardiovascular changes. To further characterize these responses we measured metabolic heat production and cardiovascular responses during an incremental infusion of adrenaline (A) in ten healthy subjects (five male; aged 21 to 27 years) and in a placebo controlled (C) study. Plasma adrenaline was unchanged during C, but increased during A (baseline 0.2 nmol/l and low, intermediate and high dose 1.0, 1.9 and 3.1 nmol/l respectively). There was a stepwise increase in metabolic heat production during A (from baseline +0.19, +0.51 and +0.77 kJ/min) with a fall during C (-0.25 kJ/min). During high dose A, plasma adrenaline correlated with increments in metabolic heat production (p < 0.05). Heart rate increased (p < 0.01) and diastolic blood pressure decreased (p < 0.01) at low dose A, and systolic blood pressure increased during intermediate dose A (p < 0.01). Forearm blood flow increased during A and C, with a greater increase in the former during high dose A (p < 0.01). Toe blood flow and toe pulp blood velocity decreased during high dose A (p < 0.05), whereas, skin capillary blood velocity increased at low (p < 0.05) and fell at high (p < 0.01) dose A. In summary, adrenaline increases metabolic heat production and limb blood flow in a dose-dependent fashion. A small increment in plasma adrenaline causes a rise in skin capillary blood flow; and at higher plasma levels blood flow in skin capillaries and arteriovenous anastomoses falls. PMID- 7994167 TI - Differential effects of prostanoid synthesis inhibitors on cicletanine-induced relaxation of isolated human epigastric arteries. AB - We have examined the influence of prostanoid synthesis inhibitors on the relaxation responses induced by cicletanine in ring preparations of isolated human epigastric arteries following precontraction induced by 10(-7) M noradrenaline. Cicletanine caused concentration-dependent relaxations, uninfluenced by the cyclooxygenase inhibitors, meclofenamate (1, 10 microM) and indomethacin (1, 10 microM) but significantly (p < 0.05) attenuated by the specific prostacyclin synthesis inhibitor, tranylcypromine (0.1-10 microM) (n > 6 in each). In contrast, cromakalim-induced relaxations were significantly attenuated by indomethacin, meclofenamate and tranylcypromine. The tranylcypromine-sensitive cicletanine-induced relaxation suggests, at least in part, the involvement of prostacyclin in the vasodilator action of cicletanine. PMID- 7994168 TI - Time-frequency analysis of slow cortical activity and cardiovascular fluctuations in a case of Alzheimer's disease. AB - The dynamics and relationship of slow cortical activity (amplitude modulation of electroencephalograph at 0.02-0.05 Hz) and cardiovascular fluctuations (0.01-0.05 Hz range) was studied by time-frequency mapping (modified Wigner distribution) in a patient with Alzheimer's disease. The amplitude modulating at rest basal alpha and theta activity (lead Oz) was exaggerated compared with control subjects. Fluctuations at respiratory and nonrespiratory (0.01-0.05 Hz) frequencies in R-R intervals and blood pressure were present and within normal range. Spontaneous hypotension (by 20 to 80 mmHg lasting 15-20 s) accompanied by cardioacceleration occurred repeatedly in the supine position and during hyperventilation. Slow cortical activity and nonrespiratory fluctuations (0.01-0.05 Hz) in blood pressure increased concurrently with hypotensions. No signs of peripheral autonomic dysfunction or malfunction of baroreceptors were observed and the vasomotor instability appeared to be of central origin. The results suggested that slow cortical activity was functionally related to the central autonomic nervous system and reflected cortico-thalamo-brainstem interaction. PMID- 7994169 TI - The head and neck discomfort of autonomic failure: an unrecognized aetiology of headache. AB - Information concerning the frequency, severity, character, location, duration, diurnal pattern of headache and ancillary symptoms were obtained in 25 patients with autonomic failure and 44 control subjects. Precipitating and ameliorating factors were identified. Autonomic failure patients had more head and neck discomfort than controls. Their discomfort was much more likely to localize in the occiput, nape of the neck and shoulder, compared with controls. There was a greater tendency for the discomfort to occur in the morning and after meals. It was sometimes less than 5 min in duration and was often associated with dimming, blurring, or tunnelling of vision. It was provoked by upright posture and relieved by lying down. Patients with severe autonomic failure and orthostatic hypotension often present with a posture-dependent headache or neck pain. Because the relationship of these symptoms to posture is often not recognized, the fact that these findings may signal an underlying autonomic disorder is underappreciated, and the opportunity to consider this aetiology for the headache may be missed. PMID- 7994170 TI - Making sense (suppression) of viral RNA-mediated resistance. PMID- 7994171 TI - Rhizobium meliloti lipooligosaccharide nodulation factors: different structural requirements for bacterial entry into target root hair cells and induction of plant symbiotic developmental responses. AB - Rhizobium meliloti produces lipochitooligosaccharide nodulation NodRm factors that are required for nodulation of legume hosts. NodRm factors are O-acetylated and N-acylated by specific C16-unsaturated fatty acids. nodL mutants produce non O-acetylated factors, and nodFE mutants produce factors with modified acyl substituents. Both mutants exhibited a significantly reduced capacity to elicit infection thread (IT) formation in alfalfa. However, once initiated, ITs developed and allowed the formation of nitrogen-fixing nodules. In contrast, double nodF/nodL mutants were unable to penetrate into legume hosts and to form ITs. Nevertheless, these mutants induced widespread cell wall tip growth in trichoblasts and other epidermal cells and were also able to elicit cortical cell activation at a distance. NodRm factor structural requirements are thus clearly more stringent for bacterial entry than for the elicitation of developmental plant responses. PMID- 7994172 TI - A plant plasma membrane proton-ATPase gene is regulated by development and environment and shows signs of a translational regulation. AB - A proton-pumping ATPase is present in the plasma membrane of plant cells where it sustains transport-related functions. This enzyme is encoded by a family of genes that shows signs of both transcriptional and post-transcriptional regulation. The regulation of pma1, one of the Nicotiana plumbaginifolia H+-ATPase genes, was characterized with the help of the beta-glucuronidase (gusA) receptor gene in transgenic plants. pma1 is active in the root epidermis, the stem cortex, and guard cells. This activity depends on developmental and growth conditions. For instance, pma1 activity in guard cells was strongly enhanced when the plant material (young seedlings or mature leaves) was incubated in liquid growth medium. pma1 is also expressed in several tissues of the reproductive organs where active transport is thought to occur but where scarcely any ATPase activity has been identified, namely in the tapetum, the pollen, the transmitting tissue, and the ovules. Several pma genes have a long 5'untranslated region (leader sequence) containing an upstream open reading frame (URF). Analysis of translational and transcriptional fusions with gusA in transgenic plants suggests that the pma1 leader sequence might activate translation of the main open reading frame, even though the URF is translated by a large majority of the scanning ribosomes. As confirmation, transient expression experiments showed that the pma1 leader causes a fourfold post-transcriptional increase of main open reading frame expression. Deletion of the URF by site-directed mutagenesis stimulated the main open reading frame translation 2.7-fold in an in vitro translational assay. These results are consistent with a regulatory mechanism involving translation reinitiation. Altogether, they suggest a fine, multilevel regulation of H+-ATPase activity in the plant. PMID- 7994173 TI - Overexpression of Arabidopsis COP1 results in partial suppression of light mediated development: evidence for a light-inactivable repressor of photomorphogenesis. AB - Arabidopsis seedlings are genetically endowed with the capability to follow two distinct developmental programs: photomorphogenesis in the light and skotomorphogenesis in darkness. The regulatory protein CONSTITUTIVE PHOTO MORPHOGENIC1 (COP1) has been postulated to act as a repressor of photomorphogenesis in the dark because loss-of-function mutations of COP1 result in dark-grown seedlings phenocopying the light-grown wild-type seedlings. In this study, we tested this working model by overexpressing COP1 in the plant and examining its inhibitory effects on photomorphogenic development. Stable transgenic Arabidopsis lines overexpressing COP1 were generated through Agrobacterium-mediated transformation. Overexpression was achieved using either the strong cauliflower mosaic virus 35S RNA promoter or additional copies of the wild-type gene. Analysis of these transgenic lines demonstrated that higher levels of COP1 can inhibit aspects of photomorphogenic seedling development mediated by either phytochromes or a blue light receptor, and the extent of inhibition correlated quantitatively with the vivo COP1 levels. This result provides direct evidence that COP1 acts as a molecular repressor of photomorphogenic development and that multiple photoreceptors can independently mediate the light inactivation of COP1. It also suggests that a controlled inactivation of COP1 may provide a basis for the ability of plants to respond quantitatively to changing light signals, such as fluence rate and photoperiod. PMID- 7994174 TI - Distinct phenotypes generated by overexpression and suppression of S-adenosyl-L methionine synthetase reveal developmental patterns of gene silencing in tobacco. AB - S-Adenosyl-L-methionine synthetase (SAM-S) catalyzes the conversion of L methionine and ATP into S-adenosyl-L-methionine. Tobacco plants that were transformed with a construct allowing high transcription levels of an Arabidopsis sam-s gene could be grouped into two main classes based on their morphology. One class developed yellow-green leaves and had high SAM-S activity and transgene mRNA levels, whereas the other class was stunted and had leather-like leaves, very low SAM-S activity, and suppressed mRNA level of the transgene. Because both overexpression and silencing of transgene expression led to distinct, abnormal phenotypes, the developmental pattern of transgene silencing was visualized. In the lower leaves, the suppressed phenotype was associated with the veins. In successive leaves, the area of the suppressed tissue increased until all newly developed leaves displayed the suppressed phenotype. In this study, a hypothesis is presented for this developmental gene silencing. Furthermore, transgenic plants with suppressed SAM-S activity had a characteristic smell, a consequence of the accumulation of L-methionine that is converted into the volatile methanethiol. PMID- 7994175 TI - Rhizobium nod factors reactivate the cell cycle during infection and nodule primordium formation, but the cycle is only completed in primordium formation. AB - Rhizobia induce the formation of root nodules on the roots of leguminous plants. In temperate legumes, nodule organogenesis starts with the induction of cell divisions in regions of the root inner cortex opposite protoxylem poles, resulting in the formation of nodule primordia. It has been postulated that the susceptibility of these inner cortical cells to Rhizobium nodulation (Nod) factors is conferred by an arrest at a specific stage of the cell cycle. Concomitantly with the formation of nodule primordia, cytoplasmic rearrangement occurs in the outer cortex. Radially aligned cytoplasmic strands form bridges, and these have been called preinfection threads. It has been proposed that the cytoplasmic bridges are related to phragmosomes. By studying the in situ expression of the cell cycle genes cyc2, H4, and cdc2 in pea and alfalfa root cortical cells after inoculation with Rhizobium or purified Nod factors, we show that the susceptibility of inner cortical cells to Rhizobium is not conferred by an arrest at the G2 phase and that the majority of the dividing cells are arrested at the G0/G1 phase. Furthermore, the outer cortical cells forming a preinfection thread enter the cell cycle although they do not divide. PMID- 7994176 TI - An alternative methylation pathway in lignin biosynthesis in Zinnia. AB - S-Adenosyl-L-methionine:trans-caffeoyl-coenzyme A 3-O-methyltransferase (CCoAOMT) is implicated in disease resistant response, but whether it is involved in lignin biosynthesis is not known. We isolated a cDNA clone for CCoAOMT in differentiating tracheary elements (TEs) induced from Zinnia-isolated mesophyll cells. RNA gel blot analysis showed that the expression of the CCoAOMT gene was markedly induced during TE differentiation from the isolated mesophyll cells. Tissue print hybridization showed that the expression of the CCoAOMT gene is temporally and spatially regulated and that it is associated with lignification in xylem and in phloem fibers in Zinnia organs. Both CCoAOMT and caffeic acid O methyltransferase (COMT) activities increased when the isolated Zinnia mesophyll cells were cultured, whereas only CCoAOMT activity was markedly enhanced during lignification in the in vitro-differentiating TEs. The induction pattern of the OMT activity using 5-hydroxyferuloyl CoA as substrate during lignification was the same as that using caffeoyl CoA. Taken together, the results indicate that CCoAOMT is associated with lignification during xylogenesis both in vitro and in the plant, whereas COMT is only involved in a stress response in vitro. We propose that CCoAOMT is involved in an alternative methylation pathway in lignin biosynthesis. In Zinnia in vitro-differentiating TEs, the CCoAOMT mediated methylation pathway is dominant. PMID- 7994177 TI - Transgenic plant virus resistance mediated by untranslatable sense RNAs: expression, regulation, and fate of nonessential RNAs. AB - Haploid leaf tissue of tobacco cultivars K326 and K149 was transformed with several transgenes containing cDNA of the potato virus Y (PVY) coat protein (CP) open reading frame (ORF). The various transgenes containing the PVY CP ORF sequence produced (1) the expected mRNA and CP product, (2) an mRNA rendered untranslatable by introduction of a stop codon immediately after the initiation codon, or (3) an antisense RNA that was untranslatable as a result of the incorrect orientation of the PVY CP ORF behind the transcriptional promoter. Homozygous doubled haploid (DH) (diploid) plants were generated, and selfed progeny from these plants were examined. Resistance was virus specific, functioning only against PVY. An inverse correlation between transgene-derived PVY transcript steady state levels and resistance was generally noted with lines expressing the untranslatable sense version of the PVY CP ORF. A collection of DH lines, derived from a single transformation event of a common haploid plant and isogenic for the PVY transgenes expressing untranslatable sense RNA, displayed different levels of PVY resistance. Lines with actively transcribed, methylated transgene sequences had low steady state levels of transgene transcript and a virus-resistant phenotype. These results are discussed within the context of sense suppression in plants. PMID- 7994178 TI - Inefficient rpl2 splicing in barley mutants with ribosome-deficient plastids. AB - Analysis of transcript accumulation and splicing in plastids of four nuclear mutants of barley revealed that the ribosomal protein L2 (rpl2) gene transcripts containing a group II intron remained entirely unspliced, whereas the intron of the ribosomal protein L16 (rpl16) gene (linked with the rpl2 gene in the same operon) was removed in the mutant plastids. Also, the transcripts of other genes containing group II introns (ribosomal protein S16 gene, rps16; NADH dehydrogenase ND2 gene, ndhB; cytochrome f gene, petD; and intron-containing reading frame 170, irf170) and of the tRNA for leucine, trnL (UAA), possessing the only chloroplast group I intron, were found to be spliced. The mutants used in this investigation are considered to be nonallelic; this excludes the possibility that a single nuclear gene is responsible for the impaired splicing of rpl2 transcripts. The mutants, however, have a severe deficiency in chloroplast ribosomes in common; this deficiency is evident from the lack of the essential ribosomal protein L2 and from an extremely low steady state level of plastid rRNAs. From these results, we conclude that a functioning translational apparatus of the organelle is a prerequisite for splicing of the chloroplast rpl2 class II intron but not for splicing of at least five other group II intron containing transcripts. This provides genetic evidence for a chloroplast DNA encoded component (e.g., a maturase) involved in the splicing of rpl2 pre-mRNA. PMID- 7994179 TI - Two classes of homeodomain proteins specify the multiple a mating types of the mushroom Coprinus cinereus. AB - The A mating type locus of the mushroom Coprinus cinereus regulates essential steps in sexual development. The locus is complex and contains several functionally redundant, multiallelic genes that encode putative transcription factors. Here, we compare four genes from an A locus designated A42. Overall, the DNA sequences are very different (approximately 50% homology), but two classes of genes can be distinguished on the basis of a conserved homeodomain motif in their predicted proteins (HD1 and HD2). Development is postulated to be triggered by an HD1 and an HD2 gene from different A loci. Thus, proteins encoded by genes of the same locus must be distinguished from those encoded by another locus. Individual proteins of both classes recognize each other using the region N-terminal to the homeodomain. These N-terminal specificity regions (COP1 and COP2) are predicted to be helical and are potential dimerization interfaces. The amino acid composition of the C-terminal regions of HD1 proteins suggests a role in activation, and gene truncations indicate that this region is essential for function in vivo. A corresponding C-terminal region in HD2 proteins can be dispensed with in vivo. We will discuss these predicted structural features of the C. cinereus A proteins, their proposed interactions following a compatible cell fusion, and their similarities to the a1 and alpha 2 mating type proteins of the yeast Saccharomyces cerevisiae. PMID- 7994180 TI - Two divergent endo-beta-1,4-glucanase genes exhibit overlapping expression in ripening fruit and abscising flowers. AB - Two structurally divergent endo-beta-1,4-glucanase (EGase) cDNAs were cloned from tomato. Although both cDNAs (Cel1 and Cel2) encode potentially glycosylated, basic proteins of 51 to 53 kD and possess multiple amino acid domains conserved in both plant and microbial EGases, Cel1 and Cel2 exhibit only 50% amino acid identity at the overall sequence level. Amino acid sequence comparisons to other plant EGases indicate that tomato Cel1 is most similar to bean abscission zone EGase (68%), whereas Cel2 exhibits greatest sequence identity to avocado fruit EGase (57%). Sequence comparisons suggest the presence of at least two structurally divergent EGase families in plants. Unlike ripening avocado fruit and bean abscission zones in which a single EGase mRNA predominates, EGase expression in tomato reflects the overlapping accumulation of both Cel1 and Cel2 transcripts in ripening fruit and in plant organs undergoing cell separation. Cel1 mRNA contributes significantly to total EGase mRNA accumulation within plant organs undergoing cell separation (abscission zones and mature anthers), whereas Cel2 mRNA is most abundant in ripening fruit. The overlapping expression of divergent EGase genes within a single species may suggest that multiple activities are required for the cooperative disassembly of cell wall components during fruit ripening, floral abscission, and anther dehiscence. PMID- 7994181 TI - The AAPT1 gene of soybean complements a cholinephosphotransferase-deficient mutant of yeast. AB - Aminoalcoholphosphotransferases (AAPTases) utilize diacylglycerols and cytidine diphosphate (CDP)-aminoalcohols as substrates in the synthesis of the abundant membrane lipids phosphatidylcholine and phosphatidylethanolamine. A soybean cDNA encoding an AAPTase that demonstrates high levels of CDP-choline:sn-1,2 diacylglycerol cholinephosphotransferase activity was isolated by complementation of a yeast strain deficient in this function and was designated AAPT1. The deduced amino acid sequence of the soybean cDNA showed nearly equal similarity to each of the two characterized AAPTase sequences from yeast, cholinephosphotransferase and ethanolaminephosphotransferase (CDP-ethanolamine:sn 1,2-diacylglycerol ethanolaminephosphotransferase). Moreover, assays of soybean AAPT1-encoded enzyme activity in yeast microsomal membranes revealed that the addition of CDP-ethanolamine to the reaction inhibited incorporation of 14C-CDP choline into phosphatidylcholine in a manner very similar to that observed using unlabeled CDP-choline. Although DNA gel blot analysis suggested that AAPT1-like sequences are represented in soybean as a small multigene family, the same AAPT1 isoform isolated from a young leaf cDNA library was also recovered from a developing seed cDNA library. Expression assays in yeast using soybean AAPT1 cDNAs that differed only in length suggested that sequences in the 5'leader of the transcript were responsible for the negative regulation of gene activity in this heterologous system. The inhibition of translation mediated by a short open reading frame located 124 bp upstream of the AAPT1 reading frame is one model proposed for the observed down-regulation of gene activity. PMID- 7994182 TI - The Arabidopsis GA1 locus encodes the cyclase ent-kaurene synthetase A of gibberellin biosynthesis. AB - The first committed step in the gibberellin (GA) biosynthetic pathway is the conversion of geranylgeranyl pyrophosphate (GGPP) through copalyl pyrophosphate (CPP) to ent-kaurene catalyzed by ent-kaurene synthetases A and B. The ga1 mutants of Arabidopsis are gibberellin-responsive male-sterile dwarfs. Biochemical studies indicate that biosynthesis of GAs in the ga1 mutants is blocked prior to the synthesis of ent-kaurene. The GA1 locus was cloned previously using the technique of genomic subtraction. Here, we report the isolation of a nearly full-length GA1 cDNA clone from wild-type Arabidopsis. This cDNA clone encodes an active protein and is able to complement the dwarf phenotype in ga1-3 mutants by Agrobacterium-mediated transformation. In Escherichia coli cells that express both the Arabidopsis GA1 gene and the Erwinia uredovora gene encoding GGPP synthase, CPP was accumulated. This result indicates that the GA1 gene encodes the enzyme ent-kaurene synthetase A, which catalyzes the conversion of GGPP to CPP. Subcellular localization of the GA1 protein was studied using 35S-labeled GA1 protein and isolated pea chloroplasts. The results showed that the GA1 protein is imported into and processed in pea chloroplasts in vitro. PMID- 7994183 TI - Alterations in the expression of osteonectin, osteopontin and osteocalcin mRNAs during the development of skeletal tissues in vivo. AB - Heterogeneity in the expression of three members of non-collagenous matrix proteins in osteogenic and chondrogenic development in vivo were investigated by in situ hybridization. Sections of several skeletal tissues from mice at various stages of development were hybridized with digoxigenin-labeled complementary RNA probes encoding osteonectin (Osn), osteopontin (Osp) and osteocalcin (Osc). In calvariae and mandibulae, Osn messenger RNA (mRNA) was detected in cells in pre osseous and osseous tissues before mineralization. Osp mRNA was found in cells attached to the mineralized bone matrix together with Osn mRNA followed by the expression Osc mRNA. In long bones, mRNAs for Osn, Osp and Osc were sequentially expressed with bone development from primary spongiosa to diaphyseal bone. In growth cartilage, Osn mRNA was observed in chondrocytes in non-mineralized cartilage, whereas Osp mRNA was detected in hypertrophic chondrocytes in mineralized cartilage matrix with a characteristic switch in expression. Osc mRNA was not detected in any chondrocytes. These results indicate that osteogenic differentiation in bone development in vivo is characterized by the sequential expression of these three genes, and suggest that these genes are expressed differentially and specifically, in association with extra-cellular matrix mineralization. PMID- 7994185 TI - Effects of endurance exercise on bone histomorphometric parameters in intact and ovariectomized rats. AB - Physical activity is important for maintenance of bone mass. The effects of exercise on bone histomorphometry were studied in 9-month-old intact (INT) and ovariectomized (OVX) rats. The rats were either kept sedentary (SED) or were exercised (EX) on a treadmill at 21 m/min for 1 h/day 5 days/week for 3 months. Bone resorption as well as formation parameters were significantly higher in OVX SED than in INT-SED rats, indicating increased bone turnover in OVX rats. In OVX rats, lower osteoclast perimeter and number, lower labeled perimeter but higher mineral apposition rate (MAR) and bone formation rate (BFR) were associated with higher trabecular bone in OVX-EX compared with OVX-SED rats. In intact rats, trabecular bone mass and osteoclast number and perimeter were not affected by exercise. Labeled perimeter was slightly lower while MAR was higher and BFR was insignificantly higher in INT-EX than in INT-SED rats. Thus, exercise resulted in fewer resorption-formation sites, as indicated by lower labeled perimeter, but higher activity of individual osteoblasts, as indicated by higher MAR, both in estrogen-depleted and estrogen-replete states. PMID- 7994184 TI - Time-related increase of biochemical markers of bone turnover in androgen deficient male rats. AB - Bone loss during androgen deficiency has been associated with accelerated bone turnover and imbalance between bone formation and resorption but the relative increase of both phenomena is not well described. Serum osteocalcin as marker of bone formation and urinary excretion of pyridinoline (PYD) and deoxypyridinoline (DPD) as markers of bone resorption were measured in both orchidectomized (ORCH, n = 8) and sham-operated (SHAM, n = 8) aged (12-month-old) male rats from 2 days before until 66 days after surgery. PYD and DPD were significantly higher in the ORCH group compared to the SHAM group starting from 21 days after surgery until the end of the experiment. Serum osteocalcin was only significantly increased in the ORCH group at 30 and 40 days. The maximal increase of serum osteocalcin was also smaller than the increase in PYD and DPD (30% versus 74% and 112%, respectively). The two markers of bone resorption were correlated with osteocalcin (r = 0.63 for PYD and r = 0.71 for DPD). Based on these results, we conclude that (1) bone resorption, as measured by PYD and DPD, increased during androgen deficiency; (2) moreover, the increase of bone resorption, as measured by DPD and PYD, was followed by a more moderate increase in bone formation as measured by serum osteocalcin, supporting the hypothesis that androgen deficiency causes accelerated bone turnover and imbalance between bone resorption and bone formation. PMID- 7994186 TI - Regulation of protein kinase C activity by phorbol ester, thrombin, parathyroid hormone and transforming growth factor-beta 2 in different types of osteoblastic cells. AB - We investigated the role of protein kinase C (PKC) in osteoblast function using a set of putative PKC modulating factors and an in situ peptide substrate-based kinase assay in different types of osteoblastic cells. Primary calvarial rat osteoblastic cells (ROB) and ROS 17/2.8 osteosarcoma cells showed an equally high PKC activity when a maximal dose of PKC-activating phorbol ester was applied. The osteosarcoma cell line UMR 106-01 showed only 5-10% of this maximal PKC activity. All 3 cell types responded to 10 U/ml thrombin with a 2-fold stimulation of PKC activity. However, no distinct direct effects of parathyroid hormone (bPTH (1 34)) or transforming growth factor-beta 2 (TGF-beta 2) were found in either of the cell types. The thrombin-induced stimulation of PKC was associated with an increase in the PTH-mediated cAMP response of ROB. Down-regulation of PKC activity was found when ROB were treated for 24 h with phorbol ester and, interestingly, also after a 24 h treatment with bPTH (1-34) and TGF-beta 2. We conclude that differences in PKC activity exist among osteoblastic cell types, which may be related to their different proliferative activity. Direct PKC activation may lead to modulation of the cAMP signaling pathway. Down-regulation of PKC activity by bPTH (1-34) and TGF-beta 2 provides an interesting possible mechanism for the long-term regulation of signal transduction. PMID- 7994187 TI - Evaluation and comparison of urinary pyridinium crosslinks in two rat models of bone loss--ovariectomy and adjuvant polyarthritis--using a new automated HPLC method. AB - A specific HPLC system was developed to assess urinary excretion of collagen crosslinks (pyridinoline (Pyr) and deoxypyridinoline (D.Pyr)) in two models of osteopenia in rats, ovariectomy and adjuvant polyarthritis. The sensitivity of this method was in the picomolar range. In ovariectomized rats, a specific model of bone resorption, Pyr and D.Pyr levels rose early, reaching a peak 2 weeks after surgery. Both levels remained raised during the whole observation period (6 weeks) with no change in the Pyr/D.Pyr ratio. So, in this high bone turnover model, hyperresorption is reflected by the parallel increase of both crosslinks resulting in a significant decrease of bone mineral density (BMD) at 6 weeks ( 7.3% vs. control). In polyarthritic rats, in the 2 post-adjuvant weeks, Pyr levels increased in parallel with inflammatory parameters, whereas D.Pyr levels remained unchanged. This is in agreement with our previous report that at the end of the 2nd week after adjuvant there is no change in bone resorption. From the 3rd week, both Pyr and D.Pyr increased. The Pyr/D.Pyr ratio was always significantly higher in polyarthritic rats. These results suggest that the early increase of Pyr level reflects non-osseous collagen breakdown and that bone resorption occurs at a later stage when D.Pyr rises, leading to a dramatic decrease of BMD at 4 weeks (-17.7% vs. control). Taken together, our results suggest that in rat as in human, urinary Pyr is a marker of bone and cartilage breakdown, whereas D.Pyr is a specific marker of bone loss. This automated method described may constitute a very useful tool to evaluate bone and/or cartilage breakdown in rats and for the assessment of protective treatments. PMID- 7994188 TI - Normal ranges for bone loss rates. AB - We reported previously that the variability in bone loss rates among postmenopausal women decreases dramatically during the first few years of followup. In this paper, we have examined the distributions of bone loss rates measured at the calcaneus, distal radius and proximal radius. The incidence of physical impairment was five times greater among women with bone loss rates faster than 2 S.D. below the mean. Because the rate of change in bone density was skewed at the lower end of the distribution (representing rapid bone loss), the influence of values at the extreme ends of the distribution were statistically removed in order to estimate the normal distribution of bone loss rates. For the convenience of clinicians, the upper and lower limits of the 90 and 70% normal ranges are presented. Because average bone loss rates vary with age, normal ranges are provided separately by age group. The width of each normal range decreased by at least half after 3 or 4 years of followup, compared to less than 1 year. Consequently, measured loss rates which were well within the normal range at 1 year were sometimes far outside the normal range for longer followup times. We conclude that followup duration has a profound effect on estimates of the normal range, and must be considered when interpreting the clinical significance of measured loss rates. PMID- 7994189 TI - In vivo effect of 17 beta-estradiol on intestinal calcium absorption in rats. AB - Previously we reported that intestinal cells contain estrogen receptors, and that 17 beta-estradiol enhanced calcium uptake by these cells in vitro. The current study was undertaken to examine the in vivo effects of 17 beta-estradiol on intestinal absorption of calcium and phosphorus. Three groups of rats were studied. Group 1 received solvent vehicle. Groups 2 and 3 received 5 micrograms and 40 micrograms 17 beta-estradiol/kg body weight/day, respectively, for 21 days. Hormone and solvent vehicle injections were given subcutaneously. Rats were fed a Teklad diet containing 0.4% Ca, 0.3% P and 3.0 U vitamin D/g during the study. Intestinal absorption of calcium and phosphorus was assessed over a 5-day period from day 15-19. Carmine red (25 mg/100 g diet) was added to the rat feed to mark the beginning and end of fecal collections. Administration of 17 beta estradiol caused an increase in intestinal absorption of calcium and phosphorus. The increase was significant only for calcium, and in the animals that received high-dose 17 beta-estradiol (P < 0.05). Serum calcium and phosphorus levels were significantly greater in 17 beta-estradiol treated than in control animals. The urinary excretion of calcium and phosphorus was also increased in a dose dependent manner by 17 beta-estradiol, and was significant for both calcium and phosphorus in animals that received high-dose 17 beta-estradiol (P < 0.05). In contrast, 17 beta-estradiol treatment did not significantly alter the serum levels of parathyroid hormone and 1,25(OH)2 vitamin D. These findings indicate that estrogen administration promotes intestinal absorption of calcium in vivo.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7994190 TI - Effects of two novel bisphosphonates on bone cells in vitro. AB - Bisphosphonates are now widely used in the treatment of bone diseases, particularly where there is uncontrolled bone resorption, as they are known to be potent inhibitors of osteoclasis. It is still unclear whether the bisphosphonates act by inhibiting osteoclast maturation or by blocking the mechanism of bone resorption, and little is known of their effects on osteoblasts. Recent studies with 3-amino-1, hydroxypropylidene-1,1-bisphosphonic acid (APD) in the treatment of osteolytic metastases in breast cancer have suggested that APD may affect osteoblasts directly. We have now investigated the effects of two novel bisphosphonates, CGP 47072 and CGP 42446A on osteoclastogenesis in fetal rat calvariae cultured on collagen gels and on human osteoblasts (hOB) cultured as explants from bone taken from patients at surgery. We also compared the action of these new bisphosphonates with that of APD, which at concentrations of 2.5 x 10( 6) M to 2.5 x 10(-10) M inhibited osteoclast recruitment, even when this was stimulated by conditioned medium from MCF7 breast cancer cells. This bisphosphonate was particularly potent if cultured with calvaria taken at 19 days gestation, when more immature osteoclast precursors are present. If calvariae from 20 days gestation were used, which contain more mature cells, it produced less inhibition. In contrast, CGP 42446A (2.5 x 10(-6) M to 2.5 x 10(-8) M) was more effective in inhibiting osteoclast maturation in calvariae from 20 days gestation than in those from 19 days. CGP 47072 had a similar pattern of effects but was less potent than either of the other two compounds. APD or CGP 42446A at 10(-5) M significantly inhibited hOB numbers and DNA synthesis, but lower concentrations had little effect. CGP 47072 did not inhibit human osteoblast replication. It is unlikely that these effects are due to calcium chelation, as none of these compounds mimicked results obtained with EDTA, which was effective only at 2.5 x 10(-6) M in reducing osteoclast size and 10(-4) M in human osteoblast cultures. These results demonstrate that all three bisphosphonates are able to inhibit osteoclast formation at low concentrations. APD may be able to influence less mature osteoclast precursors and CGP 42446A and CGP 47072 may exert their effects on the fusion of more mature precursor cells on the bone surface. At these concentrations, however, there is little or no effect on osteoblasts. PMID- 7994191 TI - Acetylcholine accumulation and release by hybrid NG108-15, glioma and neuroblastoma cells--role of a 16kDa membrane protein in release. AB - A procedure is described to fill up cells in culture with ACh and study its calcium dependent release, by-passing the synthesis steps. Whether differentiated or not with dbc-AMP, the NG108-15 cells efficiently released ACh when stimulated with calcium and ionophore A23187. The release was also studied in the parent C6 BU-1 and N18TG2 cells. It was found that C6-BU-1 released ACh much better that N18TG2 in spite of their glial origin. The internalization by NG108-15 cells of an antisense oligonucleotide probe hybridizing the 16 kDa proteolipid messenger common to mediatophore and to the V-ATPase reduced ACh release indicated a role of this proteolipid in ACh translocation. This characteristic protein was found in the membrane extract of NG108-15 cells and also in the C6-BU-1 cells, but its amount was strongly reduced in the N18TG2 cell line and in the NG108-15 cells having internalized the antisense probe. PMID- 7994192 TI - Partial purification of [3H]glutamate-associating-proteins with sensitivity to displacement by N-methyl-D-aspartate from rat brain. AB - An attempt was made to solubilize and isolate [3H]L-glutamic acid (Glu) binding sensitive to displacement by N-methyl-D-aspartic acid (NMDA) from rat brain. Brain synaptic membranes were solubilized by deoxycholic acid, followed by gel filtration with Sephadex G-25. In these turbid supernatants, significant but fragile binding was detected with a variety of radioligands related to ionotropic subclasses of receptors for excitatory amino acids. These included [3H]5-methyl 10,11-dihydro-5H-dibenzo-[a,d]cyclohepten-5,10-imine (MK-801), [3H]glycine, [3H]spermidine, [3H]Glu, [3H]DL-alpha-amino-3-hydroxy-5-methylisoxazole-4 propionic and [3H]kainic acids. Re-solubilization of turbid supernatants by Triton X-100 resulted in detection of [3H]Glu binding which was only stable for 24 h, with [3H]MK-801 binding being entirely lost. In these clear preparations after re-solubilization, Glu was exclusively effective in completely displacing [3H]Glu binding with other ligands being partially active. Furthermore, [3H]Glu binding displaceable by NMDA was eluted with 0.5 M KCl together with [3H]Glu binding insensitive to NMDA on DEAE-Toyopearl column chromatography, while fractions eluted with 0.2 M KCl had NMDA-insensitive [3H]Glu binding only. Chromatography on chelate (Zn)-Toyopearl resin resulted in elution of both NMDA sensitive and NMDA-insensitive [3H]Glu binding with 10 mM EDTA. High performance liquid chromatography revealed that NMDA-sensitive [3H]Glu binding was detected at retention times of 10-20 min when eluted from an Asahipak ES-502N column with NaCl at linearly graded concentrations up to 0.5 M. In order to detect NMDA sensitive [3H]Glu binding, however, the whole procedures needed to be completed within 24 h after re-solubilization. Accordingly, the identity of the NMDA sensitive [3H]Glu binding partially purified here is still unclear at present. The NMDA recognition domain could be more stable than the NMDA channel domain on the NMDA receptor ionophore complex under aqueous conditions. PMID- 7994193 TI - Functional interactions between glutamate and dopamine in the rat striatum. AB - The functional role of NMDA receptors in a spontaneous (locomotion) and a conditioned behaviour (reaction-time task) known to preferentially involve dopamine transmission in the ventral or the dorsal part of the striatum, respectively, was studied in the rat. The non-competitive NMDA receptor antagonist MK-801 systemically injected produced a dose-dependent increase in locomotor activity and impaired the performance of the animals trained to release a lever after a visual stimulus within a time limit by increasing the number of anticipatory errors (lever releases occurring before the stimulus onset). Similar behavioural changes were obtained after bilateral striatal microinjections of the competitive NMDA-antagonist APV into the ventral or dorsal striatum, respectively, suggesting that MK-801-induced behavioral effects after systemic injection might be mediated through a blockade of EAA transmission within the striatum. Dopamine injected in the same striatal locations induced effects similar to APV on locomotion and reaction-time performance, in agreement with the proposal for a functional antagonism between the glutamatergic and the dopaminergic transmission at striatal level. The conjoint administration of APV and dopamine directly into the striatum did not alter the behavioural effect induced by each compound injected alone showing that these effects are not additive. This latter observation actually suggests the occurrence of a functional interaction between the two neuronal systems probably acting on a common striatal target relaying dopaminergic and glutamatergic antagonistic influences on locomotion and conditioned motor behaviours. PMID- 7994194 TI - Acrylamide increases in vitro calcium and calmodulin-dependent kinase-mediated phosphorylation of rat brain and spinal cord neurofilament proteins. AB - Male Sprague-Dawley rats were administered a daily i.p. dose of 0.70 mmol/kg body weight of acrylamide, propionamide (a non-neurotoxic structural analog of acrylamide) or deionized water. Animals were sacrificed when signs of severe neurotoxicity were apparent. Neurofilaments (NFs) and endogenous kinase were isolated from the brain and spinal cord by axonal floatation. Increased in vitro Ca2+/calmodulin-dependent phosphorylation of endogenous and exogenous NF proteins and autophosphorylation of Ca2+/calmodulin protein kinase II (CaM kinase II, EC 2 7-1-37) were observed in samples from both brain and spinal cord of acrylamide treated animals compared with controls. There was no significant difference between samples isolated from propionamide-treated animals and controls. Increased calmodulin binding to brain supernatant CaM kinase II was also observed as a result of acrylamide treatment. There was no significant difference observed in the amount of antibody binding to the alpha-subunit of brain supernatant CaM kinase II between treated or control animals. These results suggest that increased CaM kinase II-dependent phosphorylation of cytoskeletal proteins may be involved in the mechanisms of acrylamide-induced neurotoxicity. PMID- 7994196 TI - Asymmetric cross-sensitization to the locomotor stimulant effects of phencyclidine and MK-801. AB - Chronic administration of a psychomotor stimulant has been shown to produce progressively enhanced effects, a phenomenon called "reverse tolerance" or sensitization. Sensitization which develops to the psychomotor stimulant effect of a drug generalizes to drugs with similar neurochemical mechanisms of action, a phenomenon called cross-sensitization. The present study compared the psychomotor stimulant effects of phencyclidine and MK-801, examined the effects of the daily injection of phencyclidine and MK-801 on locomotor activity and investigated whether reciprocal cross-sensitization occurred between phencyclidine and MK-801. Adult female Sprague-Dawley rats were used. Their locomotor activity was measured automatically for a 2 h period following drug injection. Phencyclidine and MK-801 both increased locomotor activity. Four daily injections of phencyclidine in a dose of 3.2 mg/kg i.p., or MK-801 in a dose of 0.32 mg/kg i.p., produced sensitization to locomotor activity. Moreover, MK-801 sensitized rats showed cross-sensitization to phencyclidine. However, phencyclidine sensitized rats did not show cross-sensitization to MK-801. This finding suggests that there are significant differences in the neurochemical mechanisms underlying phencyclidine induced and MK-801-induced sensitization. Phencyclidine sensitization may not be mediated by NMDA receptors. PMID- 7994195 TI - Presynaptic control of dopamine synthesis and release by excitatory amino acids in rat striatal synaptosomes. AB - Purified striatal synaptosomes were continuously superfused with L,3,5[3H]tyrosine in order to estimate the synthesis ([3H]water) and release of newly formed [3H]dopamine. In the presence of magnesium, L-glutamate, D,L-alpha amino-3-hydroxy-5-methyl-4-isoxazole-4-propionate (AMPA) and kainate, but not N methyl-D-aspartate (NMDA) and 1-aminocyclopentane-1S,3R-dicarboxylate (t-ACPD), stimulated the release of [3H]dopamine, in a dose-dependent manner. When magnesium was omitted or in the presence of AMPA, NMDA also increased the release of [3H]dopamine. The effects of AMPA and kainate were competitively inhibited by 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) or 6,7-dinitro-quinoxaline-2,3-dione (DNQX), whereas those of NMDA were reduced by 2-amino-5-phosphonovalerate (APV) or (+)-5-methyl-10,11-dihydro-5-H-dibenzo(a,d)cyclo-hepten-5,10-imine maleate (MK801). The stimulation of [3H]dopamine release by a high concentration of glutamate resulted from the concomitant activation of AMPA and NMDA receptors since this effect was potentiated by glycine and reduced by 2-amino-5 phosphonovalerate or MK801. This reduction was almost complete in the combined presence of DNQX and MK801. Surprisingly, glutamate and NMDA (in the absence of magnesium) reduced the efflux of [3H]water. The reduction of [3H]dopamine synthesis was blocked by 2-amino-5-phosphonovalerate indicating the involvement of NMDA receptors. Neither AMPA nor kainate affected dopamine synthesis. The inhibition of [3H]dopamine synthesis resulting from the stimulation of NMDA receptors was prevented when synaptosomes were continuously superfused with adenosine deaminase and quinpirole, a combined treatment known to markedly reduce the phosphorylation of tyrosine hydroxylase by cAMP-dependent protein kinase. The opposite effects of a high concentration of glutamate on [3H]dopamine synthesis and release were mimicked by ionomycin. As a working hypothesis, it is proposed that the NMDA-triggered calcium influx could lead to a reduction of tyrosine hydroxylase phosphorylation, possibly through an activation of calcineurin. PMID- 7994198 TI - Regional distribution of glycogen, glucose and phosphorylated sugars in rat brain after intoxicating doses of ethanol. AB - Ethanol and anaesthetics increase glycogen levels in the brain. However, no data have been reported about the effect of ethanol on glycogen and glucose metabolism in specific brain regions. We have studied the concentrations of glycogen, glucose, glucose 6-P, glucose 1,6-P2 and fructose 2,6-P2 and the activities of glycogen synthase, glycogen phosphorylase and glycogen phosphorylase kinase in seven brain regions of starved rats following treatment with a single dose or several doses of ethanol. Our results show that: (1) the effect of ethanol on glucose metabolism depends on whether it is given in one single dose or in a series of doses; (2) glycogen concentration increases after a single dose of ethanol but not after long exposure; (3) glucose, glucose 6-P in some areas, and the bisphosphorylated sugar, fructose 2,6-P2 significantly increase after prolonged exposure to ethanol; and (4) the enzymatic activities of glycogen metabolism are not modified after a long exposure to ethanol. In summary, these data show that ethanol may modify the use of glycogen, glucose and derivatives in brain. Moreover, the changes produced depend on the pattern of ethanol intake and the brain area considered. PMID- 7994197 TI - Effect of transient reduction of cerebral blood flow on membrane anisotropy and lipid peroxidation in different rat brain areas. AB - Light-microscopical studies revealed that oligemic hypoxia for 24 and 60 min as produced by bilateral clamping of the carotid arteries (BCCA) in normotension does not produce neuronal cell necrosis in the vast majority of rat brain. Less than 5% of cases showed a pattern of mild selective neuronal necrosis as would be expected in ischemia. However, significant changes in both lipid peroxidation (as measured by MDA formation) and membrane anisotropy (measured by DPH or TMA-DPH, respectively, as a fluorescence probe) in cortical and striatal, but not in hippocampal, membrane fractions could be measured in ex vivo studies. Twenty-four and 60 min of BCCA without reperfusion decreased lipid peroxidation in the cerebral cortex but not in the striatum. BCCA, either for 24 or 60 min, and 60 min of reperfusion produced no changes in lipid peroxidation in either structure. However, 24 and 60 min of BCCA followed by 14 days of reperfusion led to a significant increase in MDA formation in the striatum, while lipid peroxidation in the cortex was only increased after 60 min of BCCA. Cortical as well as striatal membrane anisotropy increased significantly 14 days later in rats submitted to BCCA for 24 or 60 min. The study shows an increased lipid peroxidation 2 weeks after a transient reduction in cerebral blood flow although no neuronal necrosis could be observed in general. PMID- 7994199 TI - Characterization of imidazoline binding protein(s) solubilized from human brainstem: studies with [3H]idazoxan and [3H]clonidine. AB - Imidazoline binding sites from the human brainstem were solubilized with 3-[(3 cholamido-propyl)-dimethylammonio]-1-propane-sulfonate (CHAPS). [3H]idazoxan and [3H]clonidine were used as ligands to characterize the solubilized binding sites. In both the soluble and membrane fractions, [3H]idazoxan binding was saturable, stereoselective, sensitive to imidazolines and insensitive to (-)norepinephrine and to amiloride. The affinities of [3H]idazoxan for the soluble and membrane sites were similar (KD = 25 +/- 11 nM and 20 +/- 3 nM). In both soluble and membrane fractions, the alpha 2-adrenoceptor binding being masked with ( )norepinephrine, [3H]clonidine bound to a low affinity site which was insensitive to (-)norepinephrine and which exhibited the same selectivity for various drugs as the [3H]idazoxan binding site. alpha 2-adrenoceptor binding was present in the membrane and the soluble fractions although it was difficult to detect in the soluble fraction because of inhibition of [3H]rauwolscine binding by the CHAPS detergent. PMID- 7994200 TI - Serotonin, a potent modulator of arachidonic acid turnover, interaction with glutamatergic receptor in brain cortex. AB - Brain cortex synaptoneurosomes actively incorporated [14C]arachidonic acid (AA) into lipids. Serotonin (5-HT), at a concentration range of 10 microM-1 mM, significantly stimulates the incorporation of AA mainly into phosphatidylinositol (PI) of brain cortex synaptoneurosomes. The stimulation rate of AA incorporation by 5-HT was the same in the presence and absence of lysophosphatidylinositol (LPI). However, in the absence of LPI some stimulation of AA uptake was also observed into phosphatidylcholine, phosphatidylethanolamine and phosphatidic acid. Buspirone, an agonist of 5-HT1A receptor, has a similar effect on AA incorporation into membrane lipids as serotonin itself. Moreover, ketanserin, an antagonist of 5-HT2 receptor, also induces activation of AA incorporation into membrane lipids. On the other hand, glutamate, in a concentration dependent manner, significantly inhibits AA uptake into PI and also has some inhibitory action on AA uptake into the other lipids. Serotonin itself and the agonist of 5 HT1A receptor through the activation of AA turnover counteract glutamate-induced inhibition of AA uptake into lipids of brain cortex. Our results indicated that serotonin directly, through the specific receptors, or indirectly, through the interaction with glutamatergic receptors, modulates turnover and the level of arachidonic acid in the brain. PMID- 7994201 TI - Simplified body-surface electrocardiographic maps with depolarization magnitude and direction. AB - A new technique is presented for extracting the magnitude and direction of ventricular depolarization at the body surface from surface electrocardiographic (ECG) map data. Bipolar electrocardiograms were obtained from 36 sites on the chest surface in five normal subjects. The direction and magnitude of depolarization as seen from the chest surface were calculated for 18 body-surface areas centred between electrode positions V1 and V6. Each area was bounded by three electrodes with an electrode spacing of 5 cm. A major depolarization component could be calculated for all triangular areas, with 48% of areas having a smaller second component. The area with the greatest magnitude in each subject had a depolarization vector pointing downwards and to the left, with an average angle to the horizontal of 55 degrees. This was consistent with an average angle of 51 degrees obtained from the subjects' 12-lead electrocardiograms. There was more variability in vector angle between adjacent areas on the right-hand side. At the V5/V6 areas, close to the cardiac apex, the vector component had an upwards orientation in all subjects, opposing the overall downward component of ventricular depolarization. The technique was able to determine local depolarization directions which were in agreement with the normal cardiac vector derived from standard electrocardiography. Reversal of the vector direction close to the cardiac apex and the collision of depolarization components from different directions could be detected. This simple form of body-surface mapping can reduce the essential features of depolarization to a single map, and provide information not directly available from a 12-lead electrocardiogram. PMID- 7994202 TI - Magnetization transfer in fatty and low-fat livers. AB - The magnetization transfer technique was applied to imaging of liver tissue at 0.1 T in order to examine the dependence of proton relaxation parameters on protein concentration. The effect of the fat signal on the values of these parameters was also evaluated by using the special fat/water separation method for low fields. The livers of pigs as a model for low-fat tissue and those of burbots as a model for fatty tissue were examined. For the low-fat liver tissue, the magnetization transfer rate Rwm correlated linearly with the total protein concentration very significantly (p = 0.0086). For the fatty liver, the relaxation parameters did not correlate well with the total protein concentration. After fat/water separation, the relaxation times T1 and T1w, the magnetization transfer rate Rwm and magnetization transfer contrast (MTC), measured from the water image, increased significantly. This indicates that the presence of fat in the liver will affect the measured values of magnetization transfer parameters. PMID- 7994203 TI - Comparison of extra-cellular fluid volume measurement in children by 99Tcm-DPTA clearance and multi-frequency impedance techniques. AB - Comparisons of extra-cellular fluid (ECF) volume estimates made by isotope dilution and electrical impedance techniques have been made in a group of 16 children. For each patient an estimate of ECF volume (Vt) was obtained from measurements of the blood clearance of 99Tcm-diethylene triamine penta-acetate (DPTA) which was compared with two estimates (Vi1 and Vi2) of ECF volume obtained from measurements of the whole-body electrical impedance at 50 frequencies in the range 1 kHz to 1.348 MHz and a third estimate Vh based on patient height, L, alone. The observed frequency response of the impedance measurements was fitted to a three-element equivalent-circuit model of whole-body impedance and gave a value of the ECF resistance R. Vi1 was obtained from Vi1 = a (L2/R) + b. Vi2 was given by c(W1/2L2/R)2/3 where W is the patient weight, and Vh was given by dL2 + e. The constants a, b, c, d, e were determined by comparison with Vt and were equal to 0.335 l omega m-2 (standard error = 0.01 1 omega m-2), 0.42 l (0.25 l), 0.33 l (omega 2kg-1m-4)1/2 0.007 l (omega 2kg-1m-4)1/3, 4.92 l m-2 (2.8 x 10(-5) lm-2), 0.13 l (0.41 l), respectively. Vi1, Vi2, Vh were linearly correlated with Vt (r2 = 0.98, 0.99, 0.95, respectively, p < 0.001), and upper and lower levels of agreement were given by +/- 0.95 l (Vt and Vi1), 1.44 l and -1.12 l (Vt and Vi2), +/- 1.5 l (Vt and Vh), respectively. Thus inclusion of the impedance data accounted for greater volume variation, but differences between the techniques were not significant (paired t-test and Mann-Whitney analysis) suggesting that more accurate and detailed measurements are required. PMID- 7994204 TI - Design and evaluation of a fibre-optic sensor for limb blood flow measurements. AB - A fibre-optic microbending sensor for clinical use in venous occlusion plethysmography (VOP) has been developed. The sensor utilizes the microbending principle to detect the volume expansion of a limb following venous occlusion. This principle is based on the loss of energy in an optical fibre that undergoes mechanical perturbations. A comparative study of 10 healthy subjects has been made between the new fibre-optic sensor and a mercury strain-gauge sensor. Each subject's limb blood flow was recorded 10 times. The two sensor types were positioned closely together on the same limb. The result of the study shows a high correlation (r = 0.949) verifying that the fibre-optic sensor's performance makes it a suitable alternative to the mercury strain-gauge sensor. PMID- 7994205 TI - An optical technique for the measurement of thoracic wall movement during high frequency jet ventilation. AB - Instrumentation for use in high-frequency jet ventilation is not currently capable of providing information suitable for predicting gas exchange. Whilst techniques for the accurate measurement of tidal volume during jet ventilation are now available, the relationship between tidal volume and the efficiency of gas exchange varies with frequency and inspiratory/expiratory time (I:E) ratio. We report technical details of a new non-invasive instrument capable of accurately measuring displacement of the thoracic wall at high frequencies and without electrical connection to the patient. It is hoped that use of this instrument will allow the calculation of an efficiency index for the transduction of airway pressure changes into peripheral expansion. It is also hoped that this index may be of value in predicting the gas exchange response to changes in jet parameters. PMID- 7994207 TI - Non-contact imaging of thermal properties of the skin. AB - Non-contact measurement of thermal properties of the skin was performed by using a thermovision camera and a mechanical system that provides a step change in ambient radiation temperature. A hood maintained at 20 degrees C was initially placed so as to cover the object surface towards which a thermovision camera was directed. Then the hood was quickly replaced by another hood maintained at 40 degrees C. Thermograms before, immediately after and 20 s after switching the hoods were taken. Then the image of emissivity was computed from thermograms taken before and immediately after hood switching, and the emissivity-corrected thermograms were computed by using the emissivity value obtained at each pixel. The images of the square root of the product of thermal conductivity, density and specific heat were computed from thermograms taken immediately after and 20 s after hood switching. While images of the emissivity obtained and the thermal parameter defined above contained significant noise, differences in these quantities between sites could be clearly demonstrated. PMID- 7994206 TI - Calcium mass in human aortas from autopsy. AB - We used a single-energy x-ray method and an image processing system to measure the amount of calcium salts deposited in 60 human aortas (41 male and 19 female) of ages 15-88 y. The aortas were removed at autopsy, slit lengthwise and preserved in formalin. The aortas were x-rayed while flat, together with a calibration block containing known amounts of CaHPO4. We determined the amount of calcium salt, referenced to CaHPO4, from the x-ray film with a personal computer using a frame-grabbing board. There was less calcium in the thoracic than the abdominal aorta both in males and females and those of ages less than 50 y. The coefficient of correlation for abdominal aortic calcium mass versus age in 19 females was 0.557 and in 41 males was 0.321. The higher correlation of mass with age for females may be related to differences in calcium metabolism between sexes. PMID- 7994208 TI - Non-invasive measurement of pulse wave velocity using transputer-based analysis of Doppler flow audio signals. AB - A system for the measurement of arterial pulse wave velocity is described. A personal computer (PC) plug-in transputer board is used to process the audio signals from two pocket Doppler ultrasound units. The transputer is used to provide a set of bandpass digital filters on two channels. The times of excursion of power through thresholds in each filter are recorded and used to estimate the onset of systolic flow. The system does not require an additional spectrum analyser and can work in real time. The transputer architecture provides for easy integration into any wider physiological measurement system. PMID- 7994209 TI - Measurement of plasma clotting time using ultrasonic shear waves. AB - This work presents a method that employs ultrasonic shear waves in the determination of prothrombin time (PT) and activated partial thromboplastin time (APTT), two plasma tests, during the coagulation process. Two AT-cut quartz crystal transducers are used as transmitter and receiver, with a frequency of 2.0 MHz. During the coagulation process there are random fluctuations in the amplitude of the wave transmitted through the sample of plasma that cease once the clot is formed. The time interval during which these fluctuations occur is used to indicate the coagulation time for the plasma. The method, repeated 35 times over the same plasma sample, provided for the mean of PT and APTT 12.7 s and 23.4 s with standard deviations of 0.8 s and 2.1 s, respectively. These results are in accordance with those obtained for normal plasma by means of other clinical tests. PMID- 7994210 TI - Performance measurements of an infrared digital scanning laser ophthalmoscope. AB - Direct digital acquisition of images using a scanning laser ophthalmoscope (SLO) offers several advantages over the conventional fundus camera; in particular, the ability to produce tomographic images using a confocal aperture. This note describes measurements of the performance of an SLO. Spatial resolution, measured by the modulation transfer function, MTF, was shown to be worse along the direction of scan. As expected, image uniformity was good, with a coefficient of variation of 1.9%. While the effect of using a 100 microns diameter confocal aperture instead of one with a 400 microns diameter was to reduce slice thickness from 2600 microns to 975 microns, image intensity was reduced by a factor of 30. PMID- 7994211 TI - Measuring leg ulcers using a laser displacement sensor. AB - A non-contact method for the measurement of a skin ulcer's area and volume has been developed. A commercially available laser displacement sensor is scanned across the ulcer's surface to produce a displacement image. From this image the healthy normal skin's surface is reconstructed and the area and volume found. Results of measurements made with phantom ulcers show that the method has a precision and accuracy +/- 5% of the total size. This compares favourably with results from other non-contact methods that have been published. The method of measurement is simple and reliable. At present, the time taken to produce a displacement image is lengthy but this is due to a limitation in the instrumentation, rather that a failing of the technique. The result of a preliminary measurement made on a patient's leg ulcer is presented. PMID- 7994212 TI - A combination of microendoscopy and spectrophotometry allowing real-time analysis of microcirculatory parameters during in vivo observations. AB - A combination of microendoscopy (which is a modification of endoscopy with fine rigid endoscopes) and spectrophotometry (which analyses on line the remission spectra from the endoscopic picture) is presented. This setup allows the endoscopic in vivo observation of haemodynamics as well as simultaneous on line determination of intravascular haemoglobin oxygenation. Furthermore, the clearance of intravasally applied tracers can be analysed. Application, results and further evaluation of this new technique are demonstrated in the retinal vessels of the albino rabbit. PMID- 7994213 TI - Bulimia nervosa and depression: a theoretical and clinical appraisal in light of the binge-purge cycle. AB - This review seeks to familiarize clinicians with several major theoretical perspectives on the relationship between bulimia nervosa and depression. It begins by clarifying the affective changes which occur within the binge-purge cycle. Six hypotheses relating negative affect to bulimia nervosa are then reviewed in light of these changes, with their strengths, weaknesses and clinical implications clearly outlined. The author concludes that, although none of these perspectives has received universal support, recent hypotheses which focus upon specific portions of the binge-purge cycle are best suited to integration. These include the restraint, escape and hopelessness hypotheses. An integrative model is proposed to account for data across the binge-purge cycle, to assist in understanding the maintenance of bulimia nervosa, and to guide clinical intervention. PMID- 7994214 TI - The structure of schizotypy, its relation to subdiagnoses of schizophrenia and to sex and age. AB - A growing amount of evidence suggests that the generally accepted division of schizophrenic symptomatology into positive and negative aspects should be extended to include a third major aspect, namely 'disorganization/social impairment'. As schizotypy can be seen as the non-pathological counterpart of schizophrenia, possibly brought about by the same 'schizotaxic' predisposition(s), it might be expected that the multidimensionality of schizotypy would reflect the tripartite structure seen in schizophrenia. Although the data from studies using scales to measure schizotypy do not clearly support this view, this is mainly because of the relative lack of comparability among the scales used in different studies. Results from the present study, which involve the factor analysis of items rather than scales derived from the testing of a large and diverse population of normal subjects, does, however, support the view that measures of schizotypy may be grouped in a parallel way to symptoms shown by populations of schizophrenic subjects. The suggestion may thus be made that the symptom groupings shown by schizophrenics may be seen as primary and not the secondary result of reactions to earlier phases of the illness. The role of sex and age in the determination of scores on schizotypic dimensions is also examined and show that the sex and age differences found in subdiagnostic categories in schizophrenia are reflected in dimensions of schizotypy. PMID- 7994215 TI - Assertiveness, submissive behaviour and social comparison. AB - This paper explores the relationship between a new assertiveness measure (the Scale for Interpersonal Behaviour--SIB), social comparison and submissive behaviour. The paper investigates these measures in relation to the personality traits of neuroticism and introversion. Findings suggest: (a) that social comparison may be an important variable in assertiveness and submissive behaviour and shows a strong relationship to neuroticism and introversion; (b) that submissive behaviour is not the mirror opposite of assertive behaviour; and (c) submissive behaviour seems more strongly associated with introversion and neuroticism than assertive performance. PMID- 7994216 TI - Into the dangerous world: an in vivo study of information processing in agoraphobics. AB - The differential processing of threatening information in anxious patients is now well established, but there has been little attention to situational variation in information processing. A review of the experimental literature suggests that agoraphobics should show interference in the performance of the modified Stroop task for threat words and that this interference should increase in phobic situations. In the present study, agoraphobics and normal controls carried out the Stroop task either in a safe setting or a public place. Agoraphobics showed greater interference with threat words but this interference was not affected by setting. The implications of this result are considered. PMID- 7994217 TI - Explaining why negative events will happen to oneself: parasuicides are pessimistic because they can't see any reason not to be. AB - Parasuicides (N = 18) were compared with matched controls (N = 18) on their subjective probability judgements for nine future, negative, self-relevant events. Prior to the probability judgements, subjects were asked to think of reasons why the events would or would not happen. The ease with which they were able to think of reasons was assessed by time taken to think of the first reason, number of different reasons given in 90 seconds and a subjective rating of difficulty. Relative to controls, parasuicides judged negative events to be more likely. They also showed evidence of finding it more difficult to think of why those events might not happen, but were no different from controls in their ability to think of reasons why the events would happen. The effect of thinking of reasons against negative events happening was to reduce the pessimism of parasuicides. It is suggested that parasuicide subjects may not actively anticipate future negative outcomes, but when presented with the possibilities, they judge them to be likely because of an inability to think of positive aspects of themselves or their circumstances which would prevent those events happening. PMID- 7994218 TI - Thought suppression and smoking relapse: a secondary analysis of Haaga (1989). AB - Previous research indicates that use of cognitive coping strategies in high risk situations is positively correlated with smoking cessation maintenance. Basic research on self-control of unwanted thoughts, however, suggests that mental coping efforts involving thought suppression should be ineffective. We evaluated this possibility by rescoring the articulated thoughts transcripts of 95 subjects from a one-year prospective study of smoking relapse (Haaga, 1989). Frequent use of cognitive coping tactics for reframing high risk situations (e.g. reminding oneself of negative consequences of smoking) predicted greater likelihood of continuous abstinence in the following three months (49 per cent success for those above the sample median, 20 per cent for those below the median). This effect was marginally significant at a 12-month follow-up. By contrast, thought suppression showed no association with maintenance of non-smoking. Discussion focused on complications in applying laboratory research on thought suppression and on reanalysis of cognitive assessment protocols. PMID- 7994219 TI - Coping, caring and stress: a study of stroke carers and carers of older confused people. AB - The dementias and strokes are chronic conditions often occurring at older ages. Most sufferers are cared for at home and, in this context, many research studies have described high levels of stress experienced by their carers. The present study, looking mainly at spouse carers of stroke victims (N = 36) or older confused people (N = 37), examined the possibility that the ways in which carers cope may be associated with their levels of stress and depression. A number of measures of behaviour disturbance and coping were developed and utilized. Multiple regression analyses supported the involvement of some aspects of coping in relation to carer stress and depression, particularly the coping strategy of Non-confronting and a Quality of Coping index--the former being positively and the latter negatively associated with stress and depression. Implications for intervention work with carers of stroke victims or carers of older confused people are discussed. PMID- 7994220 TI - A speech rate measure of laboratory induced affect: the role of demand characteristics revisited. AB - The study examined the effects of mood shift on a behavioural measure to investigate an ongoing question in the mood induction literature: Whether changes in performance following laboratory based mood induction procedures reflect genuine changes in affective state, or whether such changes can be generally attributed to the demand characteristics of the experimental situation. Prior to mood induction 40 subjects were assessed on self-spaced and maximal performance articulation tasks. Following mood induction articulation rates were again recorded. It was hypothesized that while there is considerable scope for experimental demands to influence self-paced tasks, by contrast maximal performance tasks should either reduce or eliminate demand characteristics. The results indicated that maximal articulation rate was sensitive to mood induction in that performance was retarded by the depressogenic procedure and accelerated by the elation-inducing procedure. Additionally, within-subject changes in speech rates correlated with conventional self-report measures of affective state. Interestingly, the speeded task appeared more sensitive to the mood manipulation than the self-paced task where demand characteristics had been expected to exert their greatest effect. It is concluded that these results corroborate the view that laboratory based induction procedures do promote true affective change and indicate that the speeded articulation task constitutes an effective indicator of that change. PMID- 7994221 TI - Changes in selective information processing with three psychological treatments for bulimia nervosa. AB - Data from a treatment trial were used to test whether interference with colour naming eating, shape and weight related words on the Stroop colour-naming task changed with treatment. Interference decreased with treatment and there was no difference between three treatments in the size of this effect. These findings suggest that interference with colour-naming words related to eating, shape and weight in subjects with bulimia nervosa may be a useful objective measure of patients' concerns about these issues. PMID- 7994222 TI - The inter-rater reliability of the Gudjonsson Suggestibility Scale (form 2). AB - The Gudjonsson Suggestibility Scale (GSS) is widely used, particularly in the preparation of court reports, to derive information on the memory, suggestibility and confabulation of criminal suspects, victims and witnesses. The inter-rater reliability of all these measures was assessed by three raters, using the data of 101 subjects who were tested on the parallel form of the scale (GSS2). The intra class correlation coefficients for all the memory and suggestibility measures were both very high (.951-.996) and highly significant (p < .001 for all measures), indicating a high level of inter-rater reliability. In contrast, whilst still highly significant (p < .001), the correlations for confabulation on immediate and delayed recall were much lower (.724 and .803, respectively). Guidelines are provided to refine the scoring of memory and suggestibility and to clarify the definition of confabulation. PMID- 7994223 TI - Effects of a health education programme with telephone follow-up during cardiac rehabilitation. AB - A health education and counselling programme was offered to myocardial infarction patients during and after hospitalization. A randomized pre-test-post-test control group design was used to evaluate the effects of the experimental intervention. During hospitalization the intervention consisted of two individual counselling sessions and two group health education sessions focusing on medication, healthy habits, anxiety and depression. On completion of these sessions, weekly telephone calls were made to patients for a period of six weeks after discharge from hospital. The intervention was offered to 30 myocardial infarction patients and their partners (the experimental group) in addition to standard medical care. Thirty control patients received standard medical care only. Two months after myocardial infarction, patients in the experimental condition reported a significantly greater increase in physical activity, and a significantly greater decrease in unhealthy eating habits. No effects were found regarding smoking cessation, anxiety and depression. Twelve months after discharge from hospital patients in the experimental condition reported a significantly greater decrease in unhealthy eating habits. No effects were found regarding smoking cessation, physical activity, anxiety and depression. In addition, two months after myocardial infarction, it was found that patients whose partners participated in the health education sessions showed a significantly greater decrease in smoking and unhealthy eating habits and a significantly greater increase in physical activity than patients with no partner participating. Twelve months after discharge the only significant result favouring the patients whose partner participated in the health education sessions concerned smoking cessation. PMID- 7994224 TI - The role of patient involvement in oral hygiene compliance. AB - Eighty-two dental patients were interviewed at the beginning of treatment in order to assess a number of psychosocial variables relevant to the prediction of compliance with treatment recommendations. Treatment consisted of cleaning, depuration and motivation. The patients were followed up after six months by measuring the development of plaque, calculus and gingivitis. In support of our hypothesis, it was found that variables that were related to patient involvement contributed strongly to the prediction of the oral health variables. The patient's visiting habits and initial attitudes were of particular prognostic value. The results with a set of variables conceptually unrelated to patient involvement were mixed and generally not as positive. Attendance at follow-up was predicted equally well by both kinds of variables, but generally not by the same variables as those that predicted oral health. PMID- 7994225 TI - Ageing and the pursuit of slimness: dietary restraint and weight satisfaction in elderly women. AB - Dieting and body dissatisfaction are highly prevalent amongst young women. In this study, dietary restraint, disinhibited eating, eating attitudes and body satisfaction were compared in elderly (ES) and young (YS) normal weight women. Dietary restraint and eating attitudes were similar across age groups. Differences between current body weight and desired body weight were equivalent for both age groups (ES, M = 10.8, SEM = 1.8 lb; YS, M = 11.3, SEM = 1.2 lb), although young women (Body Shape Questionnaire, BSQ, M = 78.5, SEM = 5.8) reported significantly greater dissatisfaction with their bodies than the elderly (BSQ, M = 61.7, SEM = 2.9). Of the elderly who had dieted, the majority had dieted five times or less, had started dieting between the ages of 40 and 50 years, and very few had dieted in their teens or twenties (< 8 per cent). Despite normal weight status, desire to lose weight and attempts to achieve this are experienced by young and old alike. PMID- 7994227 TI - Renal failure. PMID- 7994226 TI - Effects of rehabilitation exercise programmes on anxiety and depression in coronary patients: a meta-analysis. AB - In coronary patients, emotional disturbances in the sense of increased anxiety and depression have often been documented. Over the last years, there has been a growing interest in the effects of exercise on emotion. This meta-analysis, based on 13 to 15 studies on psychological effects of exercise programmes in coronary patients, showed a positive effect size both for anxiety (dmean = .3137) and depression (dmean = .4569). Nevertheless, these effect sizes have to be evaluated as less than medium by convention and in comparison to the effect size of psychotherapeutic interventions. The effect sizes on anxiety or depression were not related to methodological characteristics of the included studies, like duration of the exercise programme, time chosen for follow-up, publication year or use of control groups. But there was a significantly negative correlation between sample size and effect size. This might indicate a potential publication bias in the sense that significant rather than non-significant results may be published on small subject samples. We concluded that exercise programmes should not be considered the only treatment for emotional disturbances in coronary patients, but that they can be psychologically beneficial as an additional treatment component. PMID- 7994228 TI - The management of memory disorders in adults. PMID- 7994229 TI - Paradigm shift for graft-versus-host disease. PMID- 7994230 TI - Current knowledge about the properties of umbilical cord blood hematopoietic stem cells. PMID- 7994231 TI - Umbilical cord blood progenitor cell transplantation. The International Conference Workshop on Cord Blood Transplantation, Indianapolis, November 1993. AB - Haemopoietic progenitor cells are present in umbilical cord blood (UCB) and have been used to restore haemopoiesis in children after myeloablative therapy. UCB may possess a number of advantages over bone marrow and peripheral blood as a source of allogeneic progenitor cells, e.g. a lower incidence of graft-versus host disease and a decreased risk of transmission of infection and there is considerable interest in the establishment of large cord blood banks for use in unrelated transplants. The International Conference Workshop on Cord Blood Transplantation was held in Indianapolis in November 1993 and provided a timely opportunity to review the clinical and laboratory data relating to the use of UCB in transplantation. The results from 34 UCB transplants have been reported to the International Cord Blood Transplant Registry. Engraftment was achieved in 27 of 31 evaluable patients. Graft-versus-host disease > grade 1 occurred only in children transplanted from a one haplotype matched donor; 22 patients survive at a median of 1.5 years. Further sessions at the meeting reviewed the haemopoietic cell content of UCB, the capacity for expansion of early cells and the origin (fetal and/or maternal) and function of lymphoid cells within the graft. The conference ended with a discussion of the practicalities of cord blood banking including collection, cryopreservation, storage, HLA-typing and screening for genetic and infectious diseases. PMID- 7994232 TI - Bone marrow transplantation in children: current results and controversies.Meeting, Hilton Head Island, SC, March 1994. AB - The first meeting devoted specifically to BMT in children took place on Hilton Head Island, SC, in March 1994 and included detailed reviews of the role of BMT in the management of diseases for which it has been a subject of considerable controversy: haemoglobinopathies (thalassaemia and sickle cell disease), metabolic storage disorders and neuroblastoma. The results of BMT using marrow donors other than HLA-identical siblings were presented, including data from a number of centres on the outcome in children transplanted from mismatched family donors. Experience of the collection and transplantation of alternative sources of haemopoietic stem cells in the paediatric age group has accumulated rapidly in recent years. The results of transplantation of peripheral blood stem cells and of umbilical cord blood stem cells indicate that both approaches may soon replace BMT as first-line treatment for some malignant and non-malignant disorders in children. While gene therapy offers exciting prospects for the future, it was discussed here principally as treatment for ADA deficiency and is likely to remain a more distant, although exciting, therapeutic option for many diseases currently treated by BMT. PMID- 7994233 TI - Minimal residual disease after bone marrow transplantation for chronic myelogenous leukemia and implications for graft-versus-leukemia effect: a review of recent results. AB - Cure of leukemia by allogeneic BMT is achieved by the combined effect of the myeloablative preparative regimen and an allo-immune response of donor cells to residual leukemia termed the graft-versus-leukemia (GVL) effect. In the first year following BMT for CML, PCR used to detect the leukemia-specific BCR/ABL message frequently reveals subclinical levels of persisting leukemia. In a meta analysis of reports on qualitative PCR findings after BMT for CML in 12 recently published series, we found that for unmanipulated BMT in chronic phase, PCR detection was not associated with a higher relapse risk and that most patients became PCR negative within 2 years post-BMT. In contrast, PCR detection of BCR/ABL transcripts was a more reliable predictor in recipients of T cell depleted BMT and in those transplanted in accelerated or blastic phase of their disease. For accurate prediction of relapse, serial quantitative PCR is necessary. It could also be used to monitor efficacy of experimental treatments of relapse with interferon or donor lymphocyte transfusions. Furthermore, studies of the association of GVHD with PCR detection of BCR/ABL message may shed light on the relationship of GVL with minimal residual disease in CML. PMID- 7994234 TI - 25th anniversary of the first successful allogeneic bone marrow transplants. PMID- 7994235 TI - Regeneration of immunity and varicella-zoster virus infection after high-dose chemotherapy and peripheral blood stem cell autografts in children. AB - We assessed recovery of the immune system in 41 children who underwent high-dose chemotherapy (without total body irradiation) and autologous peripheral blood stem cell transplantation (PBSCT) for acute leukemias or non-Hodgkin's lymphoma. The analysis was in two parts. Firstly, we performed serial monitoring of regenerating subsets and blastogenesis of lymphocytes. We then reviewed the incidence of varicella-zoster virus (VZV) infection, based on the belief that this served as a clinical indication of immunological recovery. The CD4/CD8 ratio markedly decreased in all patients, with a nadir at 3 months, due to both abnormally low levels of CD4+ cells and sustained higher levels of CD8+ cells. These abnormalities were sustained for > 12 months post-graft. Within 6 months after PBSCT, all patients showed a decreased in vitro response to mitogens including PHA, Con A and PWM but these responses gradually recovered during the subsequent 6 months. All patients had a previous history of chicken pox. The actuarial incidence of VZV was 45% at 6 months and 67% at 12 months. All patients were treated with intravenous acyclovir with relief of pain and cutaneous healing within 10 days. No patient developed visceral dissemination. These findings suggest that at least in children, no major difference is apparent between immunological reconstitution in bone marrow transplantation and PBSCT. The development of minor and reversible VZV is a common event in this group of patients. PMID- 7994236 TI - Immune status and immune response to diphtheria-tetanus and polio vaccines in allogeneic bone marrow-transplanted thalassemic patients. AB - We evaluated the immune status against diphtheria (D), tetanus (T) and polio viruses (PV) and the immune response to re-administration of the respective vaccines in a series of 23 transplanted homozygous beta-thalassemic patients, aged 5-17 years (mean age 12.1 +/- 3.1 years). They had been given compulsory DT toxoids and types 1, 2 and 3 PV vaccine in infancy and had been successfully submitted to allogeneic BMT 2-6 years previously. Prior to revaccination, a high percentage of subjects (from 48% for type 2 PV to 83% for D) had antibody levels below the protective levels and low geometric mean titers (GMTs). After revaccination (three doses of DT toxoids and of inactivated PV vaccine) the percentage of subjects with protective levels of antibodies rose to 86-100% and the GMTs increased markedly. We conclude that: (1) the protection afforded by compulsory DT and PV vaccines administered in infancy is almost entirely lost in beta-thalassemic patients for several years after BMT, (2) revaccination is necessary in these subjects, and (3) at least three doses of DT and PV vaccines must be administered to recover adequate protection. PMID- 7994237 TI - Salivary and serum immunoglobulins in recipients of transplanted allogeneic and autologous bone marrow. AB - Significantly decreased levels of all classes Ig were found in saliva and serum of 85 patients before and up to 5 years after bone marrow transplantation (BMT). Salivary levels of IgG were increased before BMT in patients that died shortly after transplantation (p = 0.04). Significantly higher secretory IgA (sIgA) levels in saliva were noted in patients with malignant disorders than in those with non-malignant diseases, both before (p = 0.007) and after BMT (p = 0.011). Recipients of autologous marrow had higher levels of salivary sIgA before BMT than recipients of allogeneic bone marrow (p = 0.020). With increased BM cell dose at transplantation, lower levels of salivary IgG and albumin were found. Patients with cytomegalovirus infections after transplantation showed increased salivary IgG levels (p = 0.029). Individuals with chronic GVHD had less salivary IgM one year after BMT (median value 3.2 mg/l, p = 0.04) than those without chronic GVHD (median value 42.6 mg/l). All Ig classes in serum were decreased directly after BMT and later normalized. Salivary levels of all Ig classes except IgD fluctuated post-BMT. PMID- 7994238 TI - Monitoring of polyomavirus BK viruria in bone marrow transplantation patients by DNA hybridization assay and by polymerase chain reaction: an approach to assess the relationship between BK viruria and hemorrhagic cystitis. AB - An association between long-lasting hemorrhagic cystitis (HC) in bone marrow transplantation (BMT) patients and viral infections, mostly with reactivation of the human polyomavirus BK (BKV), is suggested by several previous reports. We have carried out a prospective study in 55 (30 allogeneic, 24 autologous, 1 syngeneic) BMT recipients with the aim of evaluating the role of BKV in this frequent complication after BMT. To overcome the well known difficulties in BK virus isolation in cell cultures, a DNA hybridization assay and the polymerase chain reaction (PCR) were used for the detection and monitoring of viral urinary shedding, respectively. The presence of human polyomavirus JC and adenovirus DNA was also sought in urine specimens. BK viruria was demonstrated in 52.7% of patients (in 53.3% allogeneic and in 54.1% autologous BMT), whereas JCV and adenovirus were seldom present. Seven cases of HC (20% in allogeneic and 4% in autologous BMT) occurred and in all cases the clinical event was associated with BKV urinary shedding. This study suggests that BKV infection alone does not invariably lead to HC in BMT patients; for HC to occur the presence of other, at present unidentified, factors seems to be necessary. PMID- 7994239 TI - Prophylaxis of toxoplasmosis infection with pyrimethamine/sulfadoxine (Fansidar) in bone marrow transplant recipients. AB - Prophylaxis against toxoplasmosis with weekly administration of pyrimethamine/sulfadoxine (Fansidar) was assessed for efficacy and toxicity in bone marrow transplant (BMT) recipients over a 21 month period. Sixty-nine of 90 consecutive seropositive patients were evaluable. Fansidar was administered from the time of established engraftment (median day 40, range days 13-100). Medication was scheduled to be continued until 6 months or longer in cases of continued immunosuppression (median 10 months, range day 72 to 22 months). No proven case of toxoplasmosis occurred in patients receiving prophylaxis. In addition, there were no cases of Pneumocystis carinii. Side-effects included BM suppression requiring cessation (n = 4) or interruption (n = 8) of therapy and rash (n = 1). To evaluate toxicity associated with prolonged therapy, 42 evaluable patients were assessed at 6 months following transplant (or at least 4 months of continuous treatment). Haematological toxicity was minimal and compounded in three patients showing moderate derangement by cytomegalovirus infection and graft-versus-host disease. Fansidar is an effective prophylactic agent against toxoplasmosis in BMT patients. PMID- 7994240 TI - Life-threatening infections occurring more than 3 months after BMT. 18 UK Bone Marrow Transplant Teams. AB - We sent a questionnaire to 22 teams performing allogeneic and autologous bone marrow transplants (BMT) in the UK enquiring about routine use of prophylactic antimicrobials post-transplant, use of CMV-negative blood products and the incidence of major infection acquired more than 3 months post-BMT. Eighteen centres (82%) responded. To prevent Pneumocystis infection 17 centres routinely gave cotrimoxazole at various doses for periods varying between 3 and 12 months (or sometimes longer if chronic GVHD was present) and six centres gave nebulised pentamidine to patients intolerant of cotrimoxazole. Six centres gave penicillin for 1-3 years to allograft patients. Thirteen centres gave only CMV-negative blood products to CMV neg/neg patients, one centre gave CMV immunoglobulin and five centres continued acyclovir to 6 months. During the period 1986-90, 818 autologous and 1007 allogeneic BMT patients were reported, of whom 113 (6.2%) developed severe infections requiring readmission to hospital. The commonest infections were CMV (n = 19), Pneumocystis (n = 12), Pneumococcus (n = 15), Pseudomonas (n = 7) and Aspergillus (n = 8). Some patients with severe infections were not receiving 'appropriate' prophylaxis. Only two of the patients with Pneumocystis were taking cotrimoxazole. We conclude that the duration of continuing prophylaxis against Pneumocystis and pneumococcal infections after BMT needs careful consideration; prophylaxis may be especially important in patients with persisting immune suppression. PMID- 7994241 TI - In vivo effects of GM-CSF and IL-3 on hematopoietic cell recovery in bone marrow and blood after autologous transplantation with mafosfamide-purged marrow in lymphoid malignancies. AB - This retrospective study evaluates the impact of GM-CSF and interleukin 3 (IL-3) on bone marrow (BM) and peripheral blood (PB) cell recovery following autologous bone marrow transplantation (ABMT) with mafosfamide-purged BM in patients with lymphoid malignancies compared with a control group receiving no colony stimulating factor. GM-CSF was administered at 250 micrograms/m2/day (8 patients) as a continuous infusion from day of autologous BMT until the absolute neutrophil count (ANC) reached 0.5 x 10(9)/l for 7 days or until day 30, whichever was first. IL-3 was administered daily starting on the first day of transplant at a dose of 1 microgram/kg/day (6 patients) and 5 micrograms/kg/day (6 patients) for 30 days. CFU-GM and BFU-E were sequentially evaluated in BM and PB at days 7, 14, 21, 28, and 56 post-graft. The neutrophil recovery (ANC > 0.5 x 10(9)/l) was significantly faster in the GM-CSF group compared with IL-3 5 micrograms, IL-3 1 microgram and control group (respectively, days 15, 21, 22, 24) (p < 0.05 to p < 0.01). Similarly, leukocyte recovery was faster in the GM-CSF group compared with control and IL-3 1 microgram groups (p < 0.01 and p < 0.05). No difference was noticed between the two IL-3 groups. Although no difference was observed in platelet recoveries (> 50 x 10(9)/l), it appeared that the GM-CSF group required more units of platelets than either the IL-3 1 microgram or 5 micrograms groups (p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7994242 TI - Vitrification of hematopoietic progenitor cells obtained from human cord blood. AB - Human cord blood mononuclear cells (MNCs) purified by Ficoll-Hypaque gradient centrifugation were cryopreserved in a vitreous state. The vitrification solution was MEM-alpha medium containing 4-8 mol/l (M) ethylene glycol (EG). A pellet of 1.5-2.0 x 10(6) MNCs was added with 10 microliters of 1 M EG and then 50 microliters of high concentration EG at room temperature (the final concentration was 4-8 M EG). The cell suspension was directly plunged into liquid nitrogen, stored for various periods and rapidly warmed in a water bath at 37 degrees C. The vitrification solution was removed by addition of MEM-alpha medium containing 1 M sucrose. The present experiments demonstrated that a vitrification solution consisting of 8 M EG produced the highest recovery rate for MNCs (89.5 +/- 8.5%), CFU-GM (66.6 +/- 20.8%) and BFU-E (66.5 +/- 22.8%) and the highest Trypan blue viability (98.7 +/- 0.4%). This ultrarapid cryopreservation method may be useful for the preservation of hematopoietic progenitor cells. PMID- 7994243 TI - Prognostic factors in patients who received autologous bone marrow transplantation for non-Hodgkin's lymphoma. Report of 104 patients from the Spanish Cooperative Group GEL/TAMO. AB - One hundred and four patients with low grade (9 patients), intermediate grade (31 patients) and high grade (64 patients) non-Hodgkin's lymphoma received an autologous bone marrow transplantation (BMT). Disease status at transplant was first complete remission (CR) in 46 patients, second CR in 14 patients, third CR in 7 patients, chemosensitive disease in 16 patients and chemoresistant disease in 21 patients. Estimated 5 year disease-free survival (DFS) for all 104 patients was 49% (95% confidence interval (CI), 36-63%) with a median follow-up of 24 months. Five year relapse rate for 80 evaluable patients was 26% (95% CI, 14 44%). The 8 year DFS and relapse for the 46 patients transplanted in first CR were 75% (95% CI, 63-82%) and 15% (95% CI, 7-33%), respectively, with a median follow-up of 27 months (range 13-104 months) and a median time to relapse of 5 months (range 4-20 months). In the univariate analysis, variables correlated with DFS were performance status at autologous BMT, disease status at autologous BMT, LDH level at autologous BMT, failure to achieve CR at diagnosis, front-line chemotherapy (1 vs 2 or more regimens) and Working Formulation. Variables correlated with relapse were disease status at autologous BMT, preparative regimen and Coiffer's index at diagnosis. Multivariate analysis showed that performance status was the only independent predictor of DFS and that disease status at autologous BMT was the best relapse predicting variable. In patients transplanted in first CR, the variables correlated with DFS were stage at diagnosis and performance status at autologous BMT.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7994244 TI - Prevention of hemorrhagic cystitis after high-dose alkylating agent chemotherapy and autologous bone marrow support. AB - High-dose cyclophosphamide (CY) is associated with a high risk of hemorrhagic cystitis. The reported frequency ranges from 6.5 to 52% despite the use of hydration protocols. The current study reports a hyperhydration and continuous bladder irrigation protocol which resulted in a very low incidence of microscopic hematuria and no reported cases of visible hematuria. Patients received baseline fluids at 200 ml/m2/h during chemotherapy. Additional fluid boluses were given if urine output fell below 200 ml/h. Bladder irrigation was performed at a rate of 1 l/h during and for 24 h after high-dose CY. Three hundred three evaluable patients with solid tumors received high-dose chemotherapy with CY at a dose of 5625 mg/m2 over 3 days. Patients also received cisplatin 165 mg/m2 and carmustine 600 mg/m2. Some patients received thiotepa 300-750 mg/m2 instead of carmustine. The overall incidence of microscopic hematuria (> 15 RBCs per high power field) was 19%, with only 11% of patients experiencing more than 50 RBCs per high power field. No patient developed visible hematuria or symptomatic hematuria requiring intervention. These results using aggressive hyperhydration and high volumes of continuous bladder irrigation are among the best reported following high-dose CY chemotherapy. PMID- 7994245 TI - European survey of bone marrow transplantation in acute promyelocytic leukemia (M3). Working Party on Acute Leukemia of the European Cooperative Group for Bone Marrow Transplantation (EMBT). AB - Acute promyelocytic leukemia (M3) is a distinct subtype of AML considered to have better response to chemotherapy and a higher cure rate than other subtypes. We analyzed the outcome for 362 M3 patients transplanted in Europe from November 1979 to December 1992 and reported to the acute leukemia registry of the European Cooperative Group for Bone Marrow Transplantation (EMBT). Of these 362 patients, 187 received an autograft, 129 in first remission (CR1) and 58 in second remission (CR2), and 175 an allograft, 142 in CR1 and 33 in CR2. Patients autografted in CR1 had at 7 years a leukemia-free survival (LFS) of 48 +/- 5%, a relapse rate (RR) of 41 +/- 5% and a probability of transplant-related mortality (TRM) of 18 +/- 6%. Patients allografted in CR1 had a LFS of 42 +/- 6%, a RR of 28 +/- 5% and a TRM probability of 42 +/- 8%. For patients transplanted in CR2, the respective figures after auto and allotransplantation were: LFS: 31 +/- 7% and 22 +/- 8%, RR: 54 +/- 8% and 64 +/- 11%, TRM: 23 +/- 9% and 40 +/- 9%. These data, which do not permit comparison between autologous and allogeneic BMT, indicate that roughly 45% of M3 patients achieving CR1 may be cured by a marrow transplant. Since the recent use of transretinoic acid-containing induction regimens has increased early control for patients with AML M3, it will be important to find out how these results affect outcome following allogeneic or autologous BMT. PMID- 7994246 TI - Minimal residual disease in bone marrow transplant recipients with chronic myeloid leukemia. AB - Bone marrow samples of 70 transplant recipients with CML were studied by Southern blot analysis and RT-PCR using a two-step procedure with nested primers. Twenty two patients were studied once and 48 were assessed on multiple occasions. All patients remained in a hematological remission during the study. The time of follow-up after the transplant ranged from 2 to 144 months with a median of 42 months. Thirty-nine patients (56%) were negative by RT-PCR and Southern blot studies at the time of their last evaluation. The proportion of RT-PCR negative patients increased with the duration of follow-up after the transplant; 36% of patients were RT-PCR negative after 1 year compared with 60% after 2 years and 78% after > or = 5 years. Patients maintained on immunosuppression had a higher probability of remaining RT-PCR positive. Age, sex, time from diagnosis to BMT, as well as acute and chronic GVHD did not influence the RT-PCR status. The majority of patients studied on multiple occasions demonstrated a stable RT-PCR and Southern blot pattern. Some showed uni- or multi-directional transitions. However, none of the patients studied progressed to a hematological relapse. RT PCR studies on colonies grown from RT-PCR positive. Southern blot negative patients confirmed that some of the clonogenic progenitors are able to produce BCR/ABL transcripts. PMID- 7994247 TI - Early detection of hematopoietic engraftment after bone marrow and peripheral blood stem cell transplantation by highly fluorescent reticulocyte counts. AB - At present, the appearance of neutrophils in the peripheral blood is considered to be the earliest sign of hematopoietic regeneration after myeloablative chemoradiotherapy. We studied erythroid regeneration in 27 allogeneic and 21 autologous marrow recipients using an automated reticulocyte counter employing a flow cytometric technique. Thereby, reticulocytes can be divided into a high, moderate and low fluorescent fraction according to RNA content. Marrow ablation caused an immediate and rapid fall in highly fluorescent reticulocytes (HFR) to zero in all patients. HFR reappeared after a median time of 7 days after allogeneic and 11 days after autologous marrow grafting. This was 7 and 2 days earlier than the appearance of first neutrophils. In allogeneic marrow recipients given erythropoetin after marrow infusion the median time to reach HFR of 0.2 and 0.5 x 10(9)/l was significantly shorter than time to reach similar absolute neutrophil counts (ANC). In allogeneic marrow recipients treated with G-CSF time to rise of HFR and ANC was almost exactly the same. Thus, automated flow cytometric reticulocyte counting allows early detection of hematopoietic regeneration and may be of clinical value for the early diagnosis of inadequate marrow function after marrow transplantation and the monitoring of erythroid regeneration under cytokine administration. PMID- 7994248 TI - 15-Deoxyspergualin controls cyclosporin- and steroid-resistant intestinal acute graft-versus-host disease after allogeneic bone marrow transplantation. AB - We report a case of cyclosporin- and methylprednisolone-resistant intestinal acute graft-versus-host disease (GVHD) after allogeneic bone marrow transplantation which responded to a new immunosuppressant, 15-deoxyspergualin (DSG). Endoscopy showed lymphoid hyperplasia with CD3+, CD4+, CD8- lymphocyte infiltration into the submucosa of the jejunum and colon. DSG effectively suppressed this intestinal acute GVHD. PMID- 7994249 TI - Severe isolated acute hepatic graft-versus-host disease with vanishing bile duct syndrome. AB - A 28-year-old man with chronic myelogenous leukaemia in blastic transformation underwent allogeneic bone marrow transplantation from his HLA-identical brother. Severe, progressive cholestatic jaundice developed from day 25 and did not respond to repeated therapy with high-dose methylprednisolone. In addition to marked cholestasis, both liver biopsy (day 69) and autopsy (day 134) findings revealed total disappearance of interlobular bile ducts in all of the portal areas, although extrahepatic manifestations of GVHD were minimal. Isolated acute vanishing bile duct syndrome can occur as the most severe form of acute hepatic GVHD. PMID- 7994250 TI - Pneumatosis intestinalis with free air mimicking intestinal perforation in a bone marrow transplant patient. AB - A case of pneumatosis intestinalis with perforation is reported in a patient after bone marrow allograft for chronic myeloid leukemia. Risk factors included the transplant, prolonged immunosuppression and neutropenia, graft-versus-host disease, extended use of corticosteroids, infection and lower gastrointestinal endoscopic biopsy. The literature is reviewed and a management plan for patients presenting with this complication is discussed. PMID- 7994252 TI - Complete remission following donor leukocyte infusion in ALL relapsing after haploidentical bone marrow transplantation. AB - A 7-month-old boy with a high risk ALL harbouring the translocation (4;11) was grafted with an haploidentical bone marrow from paternal origin. At time of relapse, 11 months after BMT, he received donor leukocyte infusions (DLI) which put him in second CR. GVHD and pancytopenia occurred 2 weeks after DLI and were fully reversed with CsA + prednisolone. Six months later, the child continues to be in second CR, off steroid therapy, without any signs of GVHD. Our limited experience indicates that a second CR can be obtained with acceptable toxicity by DLI in very high risk ALL children who have been previously grafted with haploidentical bone marrow cells. PMID- 7994251 TI - Bone marrow transplantation in Gaucher's disease: effect of mixed chimeric state. AB - The effective dose and schedule of enzyme replacement therapy for Gaucher's disease have not been definitely established. We report a case of mixed chimeric state in an allogeneic BMT patient and followed her clinical and laboratory progress. The result shows that a low but sustained glucocerebrosidase level may provide symptomatic relief for this lysosomal disorder. PMID- 7994253 TI - Fatal eosinophilic disease following autologous bone marrow transplantation. AB - A 15-year-old girl developed massive, fatal eosinophilic disease following autologous bone marrow transplantation (BMT) for Hodgkin's disease (HD). Prior to autologous BMT, the erythrocyte sedimentation rate (ESR) was elevated, with active HD, but eosinophilia was absent. Post-autologous BMT, ESR and peripheral eosinophilia were observed to correlate with respiratory symptoms. Initial evaluation revealed no recurrent tumor, infection or other identifiable etiology. A diagnosis of chronic eosinophilic pneumonia was made following lung biopsy. A complete response was initially achieved with steroid therapy; however, when steroid therapy was tapered, the eosinophilia and elevated ESR recurred with worsening respiratory symptoms. Terminally, severe pulmonary disease developed and recurrent HD was found in lung, lymph nodes and bone marrow. During episodes of eosinophilia, the patient's serum stimulated her bone marrow as well as control marrow to produce predominantly eosinophilic colonies. Eosinophilic colony production was not observed with patient's sera obtained prior to or during autologous BMT or with control sera. This patient died of eosinophilic inflammatory disease following autologous BMT. The etiology of this disease was not definitely identified but appeared to be due to an eosinophilic-stimulating factor which developed after autologous BMT. PMID- 7994254 TI - Splenectomy may reverse pancytopenia occurring after allogeneic bone marrow transplantation. PMID- 7994255 TI - What's new in blood progenitor cell autotransplants? AB - Autotransplants of blood progenitor cells are increasingly used in persons with cancer, sometimes added to bone marrow cells but increasingly in their stead. Clearly, transplants of blood progenitor cells accelerate hematopoietic recovery after high-dose therapy. However, because some residual recipient-derived hematopoiesis typically persist even after the most intensive therapy, it is not certain that long-term hematopoiesis is from the blood progenitor cell autograft. However, this issue may be unimportant since the immediate goal is short-term recovery of bone marrow function regardless of which cells are responsible for long-term recovery. This issue is, however, of considerable import were more intensive treatment to be used or where blood progenitor cells were to be used for allografts. There are some reasons to think that transplants of blood-derived cells might have a lower likelihood of returning cancer cells to the recipient, at least in some lymphomas and solid tumors, than an autotransplant of bone marrow cells. This notion is as yet unproven and may be important only when and if more effective anti-cancer pretransplant regimens are developed. The potential role of transplants of blood progenitor cells depends on how useful autotransplants prove. Whether use of blood progenitor cells rather than bone marrow cells offers any advantage requires considerable additional data and controlled trials. PMID- 7994256 TI - Cardiac arrhythmia after infusion of cryopreserved stem cells. AB - A retrospective study of the cardiovascular side-effects of 17 patients during and after receiving unpurged cryopreserved autologous bone marrow and/or peripheral blood stem cells was performed. Fourteen (82%) patients developed cardiac arrhythmia, of which 11 (65%) developed sinus bradycardia, four (24%) second degree heart block and one patient had complete heart block. The onset of sinus bradycardia occurred at 15-513 (median 56) min and the onset of heart block ranged from 30 to 680 (median 234) min after starting the stem cell infusion. Hypertension was noted in seven patients (41%) and usually occurred within 2 hours of infusion. There was no mortality or symptoms associated with these findings. Since some of these arrhythmias could be quite severe as assessed electrophysiologically, continuous cardiac monitoring should be considered during and after the infusion of cryopreserved stem cells. PMID- 7994257 TI - Ovarian recovery after total body irradiation and allogeneic bone marrow transplantation: long-term follow up of 79 females. AB - Seventy-nine females undergoing allogeneic BMT following conditioning with total body irradiation (TBI), were prospectively followed between March 1983 and March 1992 with regular gynaecological examinations, including plasma levels of luteinising hormone (LH), follicle stimulating hormone (FSH), 17-beta oestradiol (E2) and pelvic ultrasonography. The end-points of this study were the following: (1) early and late effects of TBI on ovarian function, (2) compliance and results of hormonal replacement therapy (HRT), and (3) predictive events for ovarian recovery. During the first year post-BMT most adult women complained of vasomotor and/or genitourinary tract symptoms. These were associated with decreased E2 and increased LH-FSH plasma levels and a deterioration in their sexual life (94% of sexually active women). Forty-nine adult females were selected to receive systemic hormonal replacement therapy (HRT), consisting of cyclic transdermal oestrogens plus medroxyprogesterone acetate (MPA) or cyclic oral therapy with low doses of conjugated oestrogens and MPA: these patients were selected on the basis of age (< 45 years), absence of medical contraindications or subjective refusal. Compliance and tolerability were overall good: most women (65%) never stopped HRT; this was discontinued in 14 patients for medical reasons and in 3 because of refusal. Forty-three females completed 6 months of HRT: vasomotor symptoms disappeared in 91% of 58 women who previously referred these symptoms. Improvement of genitourinary symptoms was seen both with local and systemic hormonal therapy. However sexual symptoms were reduced in 21 of 26 women (81%) given HRT compared with 8 of 19 (42%) women given local treatment (p = 0.02).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7994258 TI - Outpatient total body irradiation for bone marrow transplantation. AB - Five selected patients entering a BMT program were included in a prospective feasibility study to evaluate the tolerance to total body irradiation (TBI) on an outpatient basis. Four fractions of 3 Gy in 4 consecutive days (8 Gy lung total dose) were given. Ondansetron 8 mg/8 h orally was used without sedation as anti emetic regimen. After each treatment dose, patients went home where they remained in close telephone contact with the BMT team. After the last TBI fraction, patients were hospitalized and treated with cyclophosphamide 60 mg/g/day for 2 consecutive days. The outpatient TBI regimen was well tolerated in four cases. Only one patient presented with nausea and vomiting after the second treatment day. She was admitted to the hospital and treated with chlorpromazine. During the conditioning and hematological recovery period, no complications related to the outpatient TBI could be identified. We conclude that TBI can be given on an outpatient basis with safety. Additionally, it represents a cost saving of US$ 1160 per patient. PMID- 7994259 TI - Bone marrow transplantation in 63 adult patients with acute lymphoblastic leukemia in first complete remission. AB - Over a 10 year period, we transplanted 63 patients with acute lymphoblastic leukaemia (ALL) who had achieved first complete remission (CR). All were > 15 years old and 45 (71%) had at least one poor prognostic factor. Twenty-nine patients with a suitable sibling underwent autologous bone marrow transplantation (BMT). Beginning in 1984, patients without a donor received an allogeneic BMT (34 patients). Preparation consisted of cyclophosphamide (CY)/TBI (78%) or melphalan (Mel)/TBI (22%); marrow was treated in vitro in 31 patients (allogeneic: 7; autologous: 24). Kaplan-Meier estimates of the probability at 6 years of relapse, survival and DFS were 41% (allogeneic: 10%, autologous: 65%, p < 0.05), 44% (allogeneic: 62%, autologous: 26%, p = NS) and 42% (allogeneic: 62%, autologous: 27%, p < 0.06), respectively. This report confirms that allogeneic BMT permits long-term remissions giving high levels of survival when performed shortly after entering first CR while autologous BMT, when performed in the same setting, is less successful at preventing relapse. This study also confirms the high sensitivity of ALL to the graft-versus-leukemia effect provided by allogeneic BMT. Chemoradiotherapy dose intensification delivered at autologous BMT is not sufficient to prevent relapses. Autologous BMT must therefore be augmented by other approaches of which immunotherapy may be one. PMID- 7994260 TI - Transplantation of patients with high risk acute myeloid leukemia in first remission with autologous marrow cultured in interleukin-2 followed by interleukin-2 administration. AB - Relapse rates in patients after autologous bone marrow transplantation (BMT) for acute myeloid leukemia (AML) continue to be high despite the use of aggressive conditioning regimens. Based on studies in the murine system a clinical protocol was developed that utilizes immunotherapy to obtain a graft-versus-leukemia (GVL) effect both pre-BMT (to purge leukemic cells from the autograft) and post-BMT (to eradicate residual leukemia in the patient). As part of a phase I study, 10 consecutive patients (median age 41 years, range 15-60 years) with 'high risk' AML (i.e. any of the following: FAB M5, WBC of > or = 50 x 10(9)/l at diagnosis or 'unfavorable' cytogenetic abnormalities) were transplanted at a median of 32 days (range 13-128 days) after achieving first remission. Marrow cells to be autografted were first cultured for 8 days at 37 degrees C in standard long-term culture medium (containing 12.5% horse serum, 12.5% fetal calf serum and 10(-6) M hydrocortisone) to which 1000 U/ml of interleukin-2 (IL-2) was also added. During this time patients received busulfan 4 mg/kg for 4 days and cyclophosphamide 60 mg/kg for 2 days). On the day of transplantation (day 0), the cultured marrow cells were collected from the flasks and infused over 1 h. Between days 0 and 7 patients were given escalating doses of subcutaneous IL-2 (2, 4 and 6 x 10(5) U/m2/day, 3-4 patients/dose level). Side-effects attributable to IL-2 were generally mild, dose-dependent and consisted of fever and malaise.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7994261 TI - Addition of low-dose folinic acid to a methotrexate/cyclosporin A regimen for prevention of acute graft-versus-host disease. AB - A study was performed to determine whether the addition of folinic acid to a combination of methotrexate (MTX) and cyclosporin A (CsA) after allogeneic bone marrow transplantation (BMT) could improve tolerance to the regimen without inhibiting its ability to prevent graft-versus-host disease (GVHD). Sixty-nine adult BMT patients received CsA plus MTX 15 mg/m2 on day 1 and 10 mg/m2 on days +3, +6 and +11. Folinic acid 5 mg was started 24 h after each MTX dose and continued 6 hourly until 12 h before the next dose of MTX. The median age of the group was 37 years and 13 patients (19%) received bone marrow from mismatched and/or unrelated donors. No MTX doses were omitted or modified. Grade II-IV acute GVHD occurred in 18 patients (29%) and chronic GVHD in 35 of 56 (64%) patients at risk. There were no cases of grade > or = III stomatitis. Transplant-related mortality was 7% before 100 days and 20% overall (9% for low risk leukaemia) with a median follow-up of 41 months (range 24-88 months). This regimen of folinic acid rescue may contribute to a well tolerated GVHD prophylaxis protocol with reasonably low BMT-related mortality. Our results suggest that the ability of MTX to prevent acute GVHD is not abrogated by folinic acid given in this way. PMID- 7994263 TI - Autologous stem cell transplantation in chronic myelogenous leukemia: a retrospective analysis of the European Group for Bone Marrow Transplantation. Chronic Leukemia Working Party of the EBMT. AB - Over a 3 year period (1989-1991), 49 patients who underwent autologous stem cell transplantation (ASCT) for chronic myelogenous leukemia (CML) in chronic phase were reported to the European Bone Marrow Transplant Registry. Most patients had bad prognostic factors. The results were analyzed by 1 September 1993. Hematological recovery was observed in 45 cases and was significantly quicker after blood stem cell transplantation (n = 30) than after BMT (n = 19). Five patients died early and five other patients did not achieve a complete hematological response (CHR) following ASCT. Of the 39 patients who achieved CHR, 34 are still alive 17 to 52 months after ABSCT. Fifteen of the 34 patients who had cytogenetic evaluation exhibited a major response (> or = 65%, Ph-negative metaphases). The actuarial risk of transformation for the 44 evaluable patients was 28.1 +/- 15% (95% CI) and the actuarial survival at three years was 81.5 +/- 15% (95% CI). No factors were found to significantly influence the response rate or the patients' survival. These encouraging results suggest that ASCT by itself could play a role in prolonging survival in CML patients. PMID- 7994262 TI - Prolactin: a possible mediator of graft-versus-host disease following allogeneic bone marrow transplantation in humans. AB - We have evaluated post-transplant serum levels of prolactin with respect to source of donated bone marrow (BM) and to the occurrence of either acute and/or chronic graft-versus-host disease (GVHD). Forty adult patients underwent allogeneic (n = 35), autologous (n = 4) or syngeneic (n = 1) bone marrow transplantation for haematologic malignancy (n = 32) or aplastic anaemia (n = 8), respectively. Serum prolactin levels measured within 100 days post-transplant were related to patients' sex but otherwise proved unrelated to the occurrence or severity of GVHD and to the source of the BM graft (allogeneic, autologous, syngeneic). Beyond day 100 post-graft, however, serum prolactin levels proved significantly elevated in allogeneic recipients exhibiting chronic GVHD (p = 0.0004) and were unrelated to the patients' sex. In this group of patients, serum prolactin levels were not related to serum cyclosporin levels. In allogeneic recipients exhibiting no GVHD, serum prolactin levels were positively correlated with serum cyclosporin levels (p < 0.05). These data show that serum prolactin levels are significantly elevated beyond day 100 post-graft in recipients exhibiting chronic GVHD. Prolactin, a hormone recently shown also to be released by mononuclear leucocytes and to be involved in lymphocyte activation plays a hitherto unrecognized role in the pathogenesis of GVHD in humans. PMID- 7994264 TI - Parafollicular bulges, but not hair bulb keratinocytes, are attacked in graft versus-host disease of human skin. AB - Graft-versus-host disease (GVHD) has been shown to preferentially attack epithelial stem cell regions in the rete ridge of epidermis, the parafollicular bulge stem cells of the hair follicle, the limbus of the eye, the basal cells of filiform papilla of the tongue and the stem cell regions of gut crypts. The parafollicular bulge, but not the papillary bulb tip, has recently been shown to be the site of follicular stem cells. The hair bulb at the tip of the papilla contains progeny of the parafollicular bulge stem cells. These progeny in turn are a proliferative population which gives rise to the hair. We asked the question: Does GVHD preferentially attack the younger, less differentiated population of cells in the parafollicular bulge but spare the also cycling, later generation of cells in the papillary bulb? We had 22 evaluable cases from our prior study of 38 biopsies of GVHD patients: 19 showed preferential bulge involvement, 2 showed both involved, 1 showed neither involved and none showed bulb positive and bulge negative. The data support a strong preference for GVHD to attack the less differentiated of two cell populations both of which are cycling, thereby supporting the hypothesis that preferred targets are related to the stem cell populations in epithelial and not just all cycling or proliferating populations. PMID- 7994265 TI - Bone marrow transplantation for primary refractory acute leukaemia. AB - Twenty-four patients with primary resistant acute leukaemia received bone marrow transplants (BMTs) from matched sibling, syngeneic, matched unrelated, or mismatched family donors as treatment for induction failure. Three (12.5%) patients are alive and well 2-10 years after transplantation. Four (16.7%) patients died of transplant-related complications early post-transplant and remission status could not be determined. Two patients did not achieve complete remission (CR) and died of cytomegalovirus pneumonitis 3 months post-transplant. One patient died of graft failure. CR was obtained in 17 of 20 (85%) evaluable patients after BMT. Ten of 17 (58.8%) patients achieving CR died of transplant related complications 1-10 months post-transplant. Four of 17 (23.5%) patients who had achieved CR relapsed after transplant. We conclude that a high proportion of patients failing to achieve remission with aggressive conventional chemotherapy achieve CR with BMT and a small proportion become long-term survivors. PMID- 7994266 TI - A survey of methods of processing and storage of bone marrow and blood stem cells in the EBMT. AB - We conducted a survey to identify current practices in bone marrow processing, preservation and storage by mailing a questionnaire to 155 bone marrow transplant centres listed in the EBMT records. Approximately 57% of centres replied. There were wide variations in methodology which reflected the different types of disease being treated, local conditions and personal preferences. A number of areas where more caution could be exercised were identified: possible reinfusion of excessive quantities of heparin, possible misuse of disposable needles and lack of awareness of the implications of product liability rules relating to cooling rate, storage and viability data. PMID- 7994267 TI - Autologous transplant for chronic myelogenous leukemia using marrow treated ex vivo with mafosfamide. AB - Ten adult patients with Ph-positive chronic myelogenous leukemia (CML) received autologous transplantation using marrow treated ex vivo with mafosfamide. At transplant, 7 patients were in chronic phase (5 in first, 2 in second) and 3 in accelerated phase. The median time to achieve 500 x 10(6)/l neutrophils was 32 days (range 17-72 days). A platelet count of 20 x 10(9)/l was achieved at a median of 40 days (range 24-151 days). After transplant, cytogenetic analysis revealed 100% Ph-negative marrow metaphases in 6 of 9 analyzable patients with a median duration of Ph-negative hematopoiesis of 6.5 months. After a median follow up of 16 months (range 3-31 months), five patients evolved into blast crisis, two died of non-hematological causes, one is Ph-negative in chronic phase at +4 and one is in chronic phase, but Ph-positive, at +22. In conclusion, this pilot study demonstrates that: (1) engraftment can occur from Ph-negative stem cells selected by mafosfamide, (2) mafosfamide purging may induce a transient period of Ph negative hematopoiesis, and (3) modifications of the purging procedure and post transplant manipulations of the immune-hematopoietic system are required to prolong cytogenetic remission. PMID- 7994268 TI - Seroprevalence of HTLV-I and HTLV-II in marrow transplant recipients. AB - HTLV-I and HTLV-II can both be transmitted through blood transfusions. Although the seroprevalence of HTLV-I/II in volunteer blood donors in low, patients with leukemia who received multiple blood transfusions are at increased risk for HTLV I/II infection. Patients undergoing marrow transplantation for malignant and non malignant diseases have often received multiple transfusions prior to transplantation. The seroprevalence of HTLV-I/II in marrow transplant recipients is not known, however. We studied pre-transplant sera from 317 patients receiving allogeneic or syngeneic marrow transplant in 1988 for antibodies to HTLV-I/II using an ELISA. Six sera were positive in this assay and nine other sera had absorbance values elevated above background. One of these 15 sera was confirmed positive in a Western blot assay; six others had an indeterminate reactivity. The seropositive patient was infected with HTLV-I and not HTLV-II as determined using a synthetic peptide-based ELISA; the indeterminate sera did not show reactivity to either HTLV-I or HTLV-II in this assay. Differentiation of HTLV-I from HTLV-II infection was also shown using a modified recombinant Western blot assay in which the seropositive patient showed reactivity to recombinant HTLV-I env gp46 and not recombinant HTLV-II env gp46. These results show infection with HTLV in one of 317 patients (0.3%) prior to marrow transplantation. The clinical consequences resulting from HTLV-I/II seropositivity during the severe immunosuppression accompanying marrow transplantation are not known. Testing blood donors for HTLV I/II as is currently practised should reduce seroprevalence of HTLV-I/II in previously transfused marrow transplant recipients. PMID- 7994269 TI - Busulfan-containing pre-transplant regimens for the treatment of solid tumors. AB - This study investigated the toxicity and efficacy of busulfan-containing pre transplant regimens in patients with solid tumors. The majority of these patients were also treated on protocols involving two transplant courses aiming at further reducing tumor burden. Between October 1984 and November 1993, we treated 44 patients with recurrent breast cancer (n = 28), sarcoma (n = 10) or ovarian cancer (n = 6) with one of two busulfan-containing regimens. All patients except two had measurable disease prior to transplantation. Twenty-one patients had not received chemotherapy for metastatic disease. Of the remaining 23 patients treated with standard-dose chemotherapy, 14 had progressive disease. Busulfan 16 mg/kg was paired with cyclophosphamide 200 mg/kg (BuCY) or with etoposide 60 mg/kg (Bu-Vp). The Bu-Vp combination (32 courses) was used as the second preparative regimen in patients who had received thiotepa, carboplatin and cyclophosphamide for their first transplant. The BuCY regimen was used in 16 courses, either for single or for tandem transplant. Bone marrow cells only were used in 17 transplants and peripheral blood progenitor cells, with or without bone marrow, in 31 courses. Treatments were usually well tolerated. Common toxicities included mucositis, skin rash and veno-occlusive disease of the liver (fatal in two). One patient developed generalized seizures during busulfan therapy. Hematologic recovery was significantly accelerated with peripheral progenitor cells and permitted the administration of closely spaced tandem transplants. Two patients receiving sequential transplants with BuCY experienced severe long-term neurologic and pulmonary toxicity. Objective responses were noted in 26 patients.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7994270 TI - Phase I trial of high-dose melphalan, high-dose etoposide and autologous bone marrow re-infusion in solid tumors: an Eastern Cooperative Oncology Group (ECOG) study. AB - The purpose of this work was to determine the maximum tolerated (phase II) dose of melphalan and etoposide that can be given in conjunction with autologous BM re infusion in patients who have refractory or relapsed solid tumors. Twenty-six patients with refractory or relapsed breast cancer (n = 15), small cell lung cancer (n = 1), ovarian cancer (n = 3), colorectal cancer (n = 3) or malignant melanoma (n = 4) were enrolled and treated in this phase I study. Patients ranged in age from 31 to 60 years (median 44.5 years). Melphalan 180 mg/m2 (60 mg/m2/day for 3 consecutive days i.v. over 30 min) and etoposide 1200-3600 mg/m2 (400-1200 mg/m2/day for 3 consecutive days i.v. over 4 h) were given followed by autologous BM infusion 60-72 h after completion of chemotherapy. Ten patients received GM CSF or G-CSF therapy after marrow re-infusion. Regimen-related toxicities included fever, pancytopenia, mucositis, nausea, vomiting, diarrhea, esophagitis, hepatic dysfunction and infection. Neutrophils recovered to > 500 x 10(6)/l and platelets recovered to > 20 x 10(9)/l (without transfusions) a median of 17 days and 20.5 days after marrow infusion, respectively. Dose-limiting toxicity occurred at an etoposide dose of 3600 mg/m2, since 4 of 6 patients treated at this dose level experienced grade 4 NCI Common Toxicity Criteria (mucositis (n = 3) and infection (n = 1)). Complete responses were noted in 7 patients (breast cancer (n = 5), colorectal cancer (n = 1) and melanoma (n = 1)); partial responses were observed in 5 patients. Melphalan 180 mg/m2 and etoposide 3000 mg/m2 is a potent high-dose chemotherapy regimen with significant antineoplastic activity, particularly for breast cancer, and has acceptable toxicity when administered in conjunction with autologous BM re-infusion. PMID- 7994271 TI - A phase I-II study of high-dose thiotepa, busulfan and cyclophosphamide as a preparative regimen for allogeneic marrow transplantation. AB - Thirty adults with hematologic malignancies at high-risk for relapse were treated on a phase I-II study of high-dose thiotepa, busulfan (BU) and cyclophosphamide (CY) as the preparative regimen for allogeneic marrow transplantation. Cyclosporine and methylprednisolone or anti-CD5 ricin A chain immunoconjugate were used as graft-versus-host disease prophylaxis. Filgrastim was given from day 1 to enhance engraftment. Median follow-up time is 16 months (range 9-29 months). Grades III-IV regimen-related toxicity occurred in 5 (26%) of 19 patients treated with thiotepa 250 mg/m2 x 3, BU 1 mg/kg x 12 and CY 60 mg/kg x 2 and this was considered the maximal tolerated dose-schedule. Stomatitis and hepatoxicity were dose-limiting. All patients engrafted and had complete donor chimerism. The actuarial rate of acute graft-versus-host disease was 71% (95% CI 62-80%). The relapse rate at 1 year was 38% (95% CI 25-50%) and the actuarial survival at 1 year was 30% (95% CI 22-38%). The combination of thiotepa, BU and CY is tolerable as a preparative regimen for allogeneic marrow transplantation. PMID- 7994272 TI - Lung toxoplasmosis after HLA mismatched bone marrow transplantation. AB - We report a clinically isolated toxoplasma pneumonitis in a child treated by HLA haplo-mismatched BMT. Conditioning consisted of TBI, cytarabine and melphalan. The BM graft was T-depleted and the boy received iv moAb antiLFA1 and antiCD2. The clinical course of pneumonitis was characterised by an early onset (day 28) and a rapidly overwhelming course. Donor and recipient had pre-graft IgG Ab against toxoplasma without IgM. These Abs had completely disappeared from the serum of the patient at the time of pneumonitis. PCR amplification detected the B1 gene of Toxoplasma gondii in the patient's PBMC from day 28. PMID- 7994273 TI - Acanthamoeba meningoencephalitis after bone marrow transplantation. AB - Two patients presented with fever and nodular pulmonary infiltrates 9 and 6 months after marrow transplantation for leukemia. The second patient also had painful subcutaneous nodules that subsequently ulcerated. Both had a history of sinusitis and both had recently been treated with corticosteroids. During treatment with antibacterial and antifungal antibiotics, they developed rapid mental deterioration, coma and/or seizures. CT findings included hydrocephalus with extensive cortical and periventricular hypodensities in the first patient, and hydrocephalus with a cerebellar hemorrhage and edema in the second patient. Cerebrospinal fluid had a low glucose and elevated protein levels with few erythrocytes and little or no pleocytosis. Despite therapy with broad-spectrum antibiotics, including coverage for opportunistic infections, both patients died. Autopsy revealed Acanthamoeba species causing necrotizing meningoencephalitis, pneumonitis and adrenalitis in the first patient and causing necrotizing meningoencephalitis and dermatitis in the second patient. While these are the only reported cases of disseminated Acanthamoeba infection in marrow transplant recipients, a review of the literature suggests that this organism may be a new cause of opportunistic infections. PMID- 7994274 TI - HLA class II DNA typing and subsequent transplantation of an aplastic anemia patient using hair follicles as a DNA source. AB - Identification of HLA-DR, DQ and DP alleles at the DNA level is an important tool for bone marrow transplantation (BMT). We recently encountered an aplastic anemia patient for whom the ability of molecular HLA typing to utilize alternative sources of DNA proved to be fundamental for her treatment. After repeated failures to obtain HLA typing using peripheral blood, HLA-DR and DQ alleles were identified by molecular techniques utilizing two hairs as a source of DNA, ultimately resulting in successful BMT from a sibling donor. This case clearly illustrates the potential of DNA methodologies for HLA typing in patients whose condition precludes the use of more traditional methods. PMID- 7994275 TI - Donor B cell lymphoma of the brain after allogeneic bone marrow transplantation for acute myeloid leukemia. AB - We present a case of EBV-induced cerebral B cell lymphoproliferation of donor origin after HLA-matched allogeneic BMT for AML. The presentation was note-worthy as this 4-year-old girl was grafted after a conditioning regimen without irradiation, with an unmanipulated, HLA-matched graft. Furthermore, the cerebral mass developed long after reduction of immunosuppressive therapy following improvement of severe GVHD. To our knowledge, such cerebral lymphoproliferation, under these transplant conditions, has never been described. PMID- 7994276 TI - Partial hypopituitarism following total body irradiation in adult patients with haematological malignancy. AB - We present the endocrine parameters of two adult patients with partial hypopituitarism documented at 6 and 8 months after chemotherapy, single fraction total body irradiation (10.5 Gy) and autologous bone marrow transplantation. The hormone profiles demonstrate severe somatotroph insufficiency and impaired adrenocorticotroph secretory capacity, despite sparing of the gonadotroph compartment. We recommend stimulatory testing of hypothalamic-pituitary function from 3 months post-transplant, as basal hormonal concentrations may be equivocal, and supplementation may significantly improve quality of life. PMID- 7994277 TI - Autologous bone marrow transplantation in ALL: relapse linked to infusion of tumor cells with the back-up marrow. AB - A 41-year-old female patient with a pre-B ALL expressing 2 BCR/ABL transcripts e1/a2 and b2/a2 underwent autologous bone marrow transplantation (aBMT) with marrow grown in long-term culture (LTC) for consolidation of remission (CR). After failing to engraft on day 54 she received her back-up marrow. She engrafted by day 23 and developed a full-blown leukemic relapse 2 weeks later. She died from tumor progression 3 months after infusion of the backup marrow. Analysis of the BCR/ABL transcripts weakly positive at time of collection of the backup marrow, negative in the LTC marrow and in the patient after infusion of the LTC marrow, again positive from day 29 after infusion of the backup marrow until death, strongly suggests that infusion of residual tumor cells with the backup marrow contributed to the relapse. PMID- 7994278 TI - Severe rhabdomyolysis as a complication of peripheral blood stem cell transplantation. AB - We present a case of severe rhabdomyolysis developing after peripheral blood stem cell transplantation (PBSCT) in a 17-year-old woman with Ki-1 lymphoma. Severe muscle weakness, myoglobinemia and acute renal failure developed on day 23 following PBSCT associated with painful peripheral neuropathy. Cytomegalovirus infection may have been a contributory factor. PMID- 7994279 TI - High-titre interferon-alpha antibodies in a patient with chronic graft-versus host disease after allogeneic bone marrow transplantation. AB - In a patient undergoing allogeneic BMT for chronic phase CML, de novo chronic GVHD developed within 80 days after transplantation. Eighteen months post-BMT, high serum levels of neutralizing interferon-alpha (IFN-alpha) antibodies were detected, which persisted despite continuous immunosuppressive treatment. The antibodies were of oligoclonal or polyclonal origin, predominantly of the IgG1 type, and reacted broadly with various human IFN-alpha types, including the patients endogenous IFN-alpha, but failed to recognize natural IFN-beta and recombinant IFN-gamma. Pathogenesis and clinical impact of the IFN-alpha antibodies are unknown. Antibodies of cytokines are a novel class of autoantibodies that may develop after allogeneic BMT and interfere with cytokine homeostasis and immune regulation. PMID- 7994280 TI - Heparin-induced thrombocytopenia after bone marrow transplantation: report of two cases. AB - Persistent thrombocytopenia and thrombotic complications are commonly observed in bone marrow transplant (BMT) patients. We describe two incidents following BMT in which heparin may have played a contributory role. One patient developed subclavian venous thrombosis following autologous BMT in spite of the severe thrombocytopenia. The second patient, who received an HLA-matched sibling allogeneic BMT, developed thrombocytopenia after a normal platelet recovery. Because of the clinical evidence and a normocellular bone marrow biopsy result, heparin-induced thrombocytopenia was suspected and heparin was discontinued. In 2 weeks, the patient was transfusion free and her platelet count returned to normal levels. These two cases demonstrate that heparin-induced thrombocytopenia may be responsible for some cases of post-BMT thrombocytopenia and thrombosis. PMID- 7994282 TI - Malignant fibrous histiocytoma secondary to allogeneic bone marrow transplantation. PMID- 7994281 TI - Prevention of transplant-related hemorrhagic cystitis using bladder irrigation with sorbitol. PMID- 7994284 TI - Quality assurance in the irradiation of blood products. PMID- 7994283 TI - Prevention of high dose L-PAM-induced mucositis by cryotherapy. PMID- 7994285 TI - National Advisory Committee on Immunization (NACI). Supplementary statement on newly licensed Haemophilus influenzae type B (HIB) conjugate vaccines in combination with other vaccines recommended for infants. PMID- 7994286 TI - Ostrich fern poisoning--western Canada and New York, 1994. PMID- 7994287 TI - An improved method for analysis of technetium radiolabeled antibody by size exclusion HPLC. AB - A quantitative radio HPLC method for the analysis of radiolabeled 99mTc compounds, in particular labeled antibodies or proteins, is described. The method is based on the quantitative re-oxidation of the reduced column absorbed 99mTc species to pertechnetate using hydrogen peroxide. The pertechnetate is quantitatively eluted from the column. The method can be used as a stand alone technique for determining the true radiolabeling yield of labeled proteins/antibodies. The method has been automated for routine use and the typical analysis time is 30 min. PMID- 7994288 TI - In vivo measurements of bone lead content in residents of southern Ontario. AB - In 111 subjects not occupationally exposed, bone lead content increased steadily with age in both men and women. Higher than expected bone lead levels were observed in two-thirds of 27 subjects working in occupations with potential for lead exposure. Five of 8 patients who displayed symptoms which might have been due to lead poisoning had increased bone lead levels. In vivo bone lead measurements reflect the cumulative extent of exposure to environmental and occupational sources of lead and allow the assessment of abnormal exposures. PMID- 7994289 TI - Synthesis, radiolabelling and stability of radioiodinated m-iodobenzylguanidine, a review. AB - Since the introduction of radioiodinated m-iodobenzylguanidine in 1980, much research has been performed, both in the chemical field as well as in medical sciences. This paper reviews the synthesis, radiolabelling and stability of radioiodinated m-iodobenzylguanidine. Regarding the many radiolabelling procedures for m-iodobenzylguanidine, the Cu(1+)-assisted nucleophilic exchange radioiodination can be considered as the method of first choice. Quality control of the radiopharmaceutical product is discussed and attention is paid to recent studies regarding the radiochemical stability of iodine-131 labelled m iodobenzylguanidine. PMID- 7994290 TI - Treatment approaches for developmental apraxia of speech. AB - The purpose of this article has been to present a theoretical construct that would enhance our understanding of the basis of the disorder apraxia of speech, whether it be developmental or acquired. From a theoretical explanation a conceptual framework was developed to guide the selection of appropriate treatment strategies. DAS, like acquired apraxia of speech, is conceived here as a sensorimotor impairment. The sensorimotor impairment is based on reduced or aberrant reafference. Thus, tactile or kinesthetic methods of treatment, as well as treatment techniques that may facilitate the processing of peripheral sensation (such as slowed speech), have been proposed as being the most facilitative. The hypotheses proposed herein require extensive investigation. Nonetheless, according to a number of clinical reports, methods that highlight movement sequences and methods that heighten the melodic line and slow rate are the ones that have gained the greatest favor in the treatment of children with DAS and adults with acquired apraxia of speech. PMID- 7994291 TI - Motor Speech Treatment Hierarchy: a systems approach. AB - The Motor Speech Treatment Hierarchy used to guide PROMPT intervention represents a theoretical framework for the application of all bottom-up motor speech treatments. In addition, the hierarchy can be used prior to motor speech treatment to evaluate what aspects of the child's neuromotor system are intact and which elements are operating ineffectively or partially. When consideration is given to the development of the speech motor system and the interaction among the various valves and/or articulators, it becomes apparent that treatment must focus on the integration of all these aspects in order to be successful. The goal of intervention must be the voluntary control of all speech actions. But voluntary control of all speech actions is not possible for all children, and the clinician must realize that compensatory actions, although beneficial in the short term, will limit more complex interactions later. It is for these reasons that more attention should be given to mastery of control at the lower stages of the hierarchy. The clinician should not assume that all actions are intact based upon the perceived quality of speech. For the child with "pure" DAS, intervention usually begins at stage V or VI, whereas for children with developmental dysarthria, intervention begins at lower levels of the hierarchy. The responsibility, as always, lies with the clinician to determine the most appropriate level at which intervention should begin and the steps needed to achieve the best speech production. The clinician's knowledge provides the foundation for changing deviant motor speech patterns and for providing for our clients voluntary control of motor speech function. It has been the aim of this article to provide for clinicians a framework for treatment that will enhance their clinical effectiveness. PMID- 7994292 TI - A clinical perspective: melodic intonation therapy for developmental apraxia. AB - The therapeutic process is a mix of technique and insight, and effective clinicians are able to blend theory with practice. This is especially true in the area of DAS. Children with the symptom complex of apraxia are a challenge to any therapy program. Clinicians should choose combinations of therapy protocols that best serve the child. MIT is one technique that has been shown to be successful. PMID- 7994293 TI - Adapted cuing technique: facilitating sequential phoneme production. AB - ACT is a visual cuing technique designed to facilitate dyspraxic speech by highlighting the sequential production of phonemes. In using ACT, cues are presented in such a way as to suggest sequential, coarticulatory movement in an overall pattern of motion. While using ACT, the facilitator's hand moves forward and back along the side of her (or his) own face. Finger movements signal specific speech sounds in formations loosely based on the manual alphabet for the hearing impaired. The best movements suggest the flowing, interactive nature of coarticulated phonemes. The synergistic nature of speech is suggested by coordinated hand motions which tighten and relax, move quickly or slowly, reflecting the motions of the vocal tract at various points during production of phonemic sequences. General principles involved in using ACT include a primary focus on speech-in-motion, the monitoring and fading of cues, and the presentation of stimuli based on motor-task analysis of phonemic sequences. Phonemic sequences are cued along three dimensions: place, manner, and vowel related mandibular motion. Cuing vowels is a central feature of ACT. Two parameters of vowel production, focal point of resonance and mandibular closure, are cued. The facilitator's hand motions reflect the changing shape of the vocal tract and the trajectory of the tongue that result from the coarticulation of vowels and consonants. Rigid presentation of the phonemes is secondary to the facilitator's primary focus on presenting the overall sequential movement. The facilitator's goal is to self-tailor ACT in response to the changing needs and abilities of the client.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7994294 TI - Rate control therapy for developmental apraxia of speech. PMID- 7994295 TI - Can religious health systems still go it alone? PMID- 7994296 TI - AMA: 4 million American women abused annually. PMID- 7994297 TI - Federal dollars give IS vendors a research boost. PMID- 7994298 TI - Deadly pathogens beware! PMID- 7994299 TI - Union continues push for FDA to mandate safer needles. PMID- 7994300 TI - New power strategies (the battle for control). AB - When yesterday's home care company has become today's primary care network, and yesterday's purchaser is today's provider, it's no longer enough to look at hospital/physician integration for clues to the new health care road map. Instead, it's vital to examine how all the players in the health care system are interacting, and what the interchanges of power and activity among them mean. In a probing analysis, Contributing Editor Alden Solovy applies an innovative macroeconomic theory to the radical reshaping of health care now taking place. PMID- 7994301 TI - Union uprising. California nurses react aggressively to work redesign. PMID- 7994302 TI - Southwest symbiosis. In Tucson, academic and community doctors tie their fates together. PMID- 7994303 TI - TQM: merger trailblazer? Quality tools provide common ground for 'doing the deal'. PMID- 7994304 TI - Chicago. Market evolution gains momentum in the Windy City. PMID- 7994305 TI - Ready or (probably) not: the elderly are coming. PMID- 7994306 TI - Spirited team. Interview by Jill L. Sherer. PMID- 7994307 TI - Radical cost cutting. PMID- 7994308 TI - Keeping promises on Medicare. PMID- 7994309 TI - [Assisted embryonal hatching]. PMID- 7994310 TI - [Evaluation of the respective roles of FSH and LH in ovulation induction]. PMID- 7994311 TI - [Sperm analysis]. PMID- 7994312 TI - [Growth factors: a pluripotent and misnamed family]. AB - Growth factors are a family of polypeptides with a major physiological role. They were first described for their mitogenic activity. However, these peptides have a wide spectrum of biological actions which include the regulation of tissue morphology, differentiation, movement and functional activity. They act via an autocrine or paracrine mechanism. They are characterized by their binding to specific receptors at the membrane level. Some of these receptors possess a kinase activity. PMID- 7994314 TI - [Initial stages of gonadal differentiation]. AB - Morphological differentiation of gonads results within successive morphogenetic steps beginning with the formation of the undifferentiated gonad, identical in both sexes, through the differentiation of the characteristic gonadal structures, seminiferous tubes in the testis and follicles in the ovary. In this paper, we report recent data on each of these steps and particularly on the origin of somatic gonadal cells. Results from our laboratory are summarized with special emphasis on the relationships between cellular differentiation and morphogenetic processes. PMID- 7994313 TI - [Signal transmission modalities induced by growth factors: from membrane to nucleus]. AB - Growth factors transduce their biological signals through transmembrane receptors that possess an intrinsic or an associated protein-tyrosine kinase activity. Two complete signalling pathways, from membrane to nucleus, were elucidated in 1993. They are described in detail in this review. PMID- 7994315 TI - [Functional interactions between somatic cells in the male gonad]. AB - The existence of multiple interactions between somatic cells in the testis, has been suspected in vivo, and demonstrated in vitro by cocultures and cultures in the presence of conditioned media. Long term Sertoli-Leydig cell interactions results in a local regulation of the specific differentiated functions of these cells, and more precisely in a control of their responsiveness to their respective gonadotropin. Among the paracrine and/or autocrine factors, growth factors are involved in the control of differentiated functions. It is the case for IGF-I and TGF-beta, which respectively exhibit a stimulatory and inhibitory effect on Leydig cell functions and more specifically on LH responsiveness. PMID- 7994316 TI - [Insulin-like growth factors and gonadal regulation in fish]. AB - Recent data showing the occurrence of IGF in fish, mainly teleostean fish, and their biological activity in gonads are reviewed. IGF-I does occur in all vertebrates and first evidence of IGF-II occurrence in fish has been reported. IGF-I is expressed in the testis and the ovary, and receptors for the peptide have been demonstrated in both gonads. Besides, IGF-I seems implied in spermatogonial proliferation and in oocyte maturation. Both germinal cells and somatic cells could be responsive to IGF-I stimulation. PMID- 7994317 TI - [IGF(s) and testicular functions. Secretion and action of IGF-1 on Leydig cells]. AB - Many in vitro and in vivo studies have demonstrated a presence of IGF-I in the testis. Testicular production of IGF-I and its mRNA is stimulated largely by gonadotropins; FSH acts on Sertoli cells while LH acts on Leydig cells. A regulation by local factors is also demonstrated; the role of GH remains unclear. In the testis, IGF-I has various effects but we only focussed this review on Leydig cells. Specific receptors have been characterized on these cells. They are up-regulated by LH/hCG (at the transcriptional level) and down regulated by IGF I. The effect of GH is depend on the experimental models used. In addition in this paper, we have shown in adult rats that the IGF-I level in the testicular interstitial fluid and the IGF-I receptors on Leydig cells are modified by fasting. Both in vivo and in vitro, IGF-I increased LH/hCG receptors and the steroidogenic response to hCG by a mechanism which is poorly understood yet. PMID- 7994318 TI - [TGF beta (transforming growth factor beta) and its related peptides in the local control of the testicle]. AB - Recent data on TGF beta (and related peptides) expression and action in the testis are briefly reviewed. At least, three isoforms of TGF beta are expressed during the male gonadal development. TGF betas are expressed in somatic and germ cells. The expression of the different isoforms varies during gonadal development and is cell specific. Both types I, II and III TGF beta receptors have been localized in somatic cells. TGF beta inhibits gonadotropin action both in Sertoli cells and Leydig cells as well as proliferation of germ cells and Leydig cells. Inhibins and activins (in terms of mRNA and proteins) are expressed in somatic cells and germ cells. Inhibin production in Sertoli cells is under the control of FSH, local factors (ex: EGF, insulin, opiods) and probably of germ cells. Activins and inhibins regulate Leydig and Sertoli cells activities and germ cells development. The existence of activin receptors in somatic and germ cells has been suggested by the presence of type II receptor mRNA (ActRII and ActRIIB). PMID- 7994319 TI - [Inhibin, activin, follistatin, and transforming growth factor beta (TGF-beta): presence in the ovary and possible role in the regulation of folliculogenesis in primates]. AB - The aim of this review is to provide recent data concerning the ovarian production of the inhibin-related peptides and their possible role in the regulation of ovarian folliculogenesis in primates. Activin is mainly produced by recruitable follicles, whereas inhibin, FSP and TGF-beta are mainly produced by preovulatory follicles. Activin could play a key role in the selection of the follicle destined to ovulate by enhancing the responsiveness of granulosa cells to FSH. Activin inhibits production of aromatizable androgens by theca interna cells but, by stimulating the FSH-induced aromatase at the level of granulosa cells, it prepares the early selected follicle to play its further endocrine function. The full endocrine function of the preovulatory follicle is triggered, among others, by inhibin which strongly stimulates the production of aromatizable androgens by theca interna cells, by TGF-beta which may favour cytodifferentiation of granulosa cells, and by FSP which, by binding activin, suppresses the negative actions of activin on preovulatory maturation. PMID- 7994320 TI - [Action of growth factors on the ovary in the domestic chicken (Gallus domesticus)]. AB - An original method for the culture of granulosa and thecal cells of the domestic hen was developed and used to investigate the effects of serum, of EGF and of IGFI on the multiplication of these cell types and on their secretion of steroid hormones. The growth of the cultures (measured by the accumulation of DNA in the culture wells) over a 72 hour period was judged to be satisfactory although slower without serum. Both growth factors stimulated cell growth and EGF inhibited steroidogenesis in both cell types. IGFI inhibits the secretion of oestrogens by thecal cells but it stimulates the secretion of progesterone by granulosa cells towards the end of the period of culture. PMID- 7994322 TI - Valuing future benefits. AB - This paper reports the results of a study of time preference amongst the general public in the Grampian region of Scotland. The subjects, who were selected randomly from the electoral roll, were offered a series of intertemporal choices. Their responses were used to calculate private financial time preference rates, social non-monetary time preference rates and social financial time preference rates. The paper investigates the relationship between these three measures of time preference in both the short and the long run. It also explores the effects of individual characteristics, including age, and health, on the implicit discount rates. PMID- 7994321 TI - Life quality assessment of breast cancer patients receiving adjuvant therapy using incomplete data. AB - Previous research on the effects of adjuvant treatment for women with operable breast cancer focused exclusively on disease-free and overall survival. In this study we evaluate life quality of premenopausal node-positive breast cancer patients receiving adjuvant chemotherapy for at least three months. For the first time, a modified latent variable model is used to assess treatment outcome in a prospective clinical trial. This poses a number of econometric problems which did not occur in the preceding studies. One of them is how to deal with patients whose records are incomplete. The data are provided by the International Breast Cancer Study Group (study VI). The results indicate that the lowest dose treatment improves life quality faster than the remaining three alternatives. At the end of the 24 months observation period no significant differences between the four treatment options remain. Although the lowest dose treatment is also the least costly no definite conclusion regarding cost-effectiveness can be drawn at this stage since survival data is not yet available. PMID- 7994323 TI - Is it possible to reduce tobacco consumption via alcohol taxation? AB - Recent studies with Spanish data suggest that indirect taxation is a potential instrument to reduce tobacco consumption but the magnitude of the estimated price elasticity limits the effectiveness of the taxes. However, if the separability restriction does not hold between tobacco and other goods, the results obtained could be misleading. This shortcoming of previous analyses leads us to formulate a demand system with alcohol, tobacco and other goods so as to estimate and test complementary effects and to assess the possibility for reducing consumption by indirect taxation of complementary commodities. We use the Spanish Family Expenditure Survey to carry out a cross-section study which allows us to estimate demand models under different assumptions about the nature of zero expenditures and to test the effectiveness of indirect taxation. The findings tend to support our initial suspicions about the inadequacy of imposing separability and point out the importance of alcohol taxation to reduce tobacco consumption. However, given the structure of the data used, these results should be viewed with caution and must be confirmed by additional evidence. PMID- 7994324 TI - Reimbursing insurance carriers: the case of 'MUFACE' in the Spanish health care system. AB - This article aims at contributing to the analysis of financial incentives in managed competition, on the basis of the literature on procurement and regulation under incomplete information. More specifically, we focus on MUFACE, the publicly funded health care system for Spanish civil servants and dependants. MUFACE makes up an internal market, where competing public and private insurers are reimbursed a flat capitation payment. Some of our results are that theoretically, both pre contractual (adverse) selection of insurers contracted by MUFACE, and post contractual risk selection of enrollees undertaken by insurers, should occur under flat capitation. PMID- 7994325 TI - Willingness to pay for diagnostic services. A new approach to modelling patient benefits in health care. AB - The paper investigates the benefit the patient derives from medical diagnosis. By considering explicitly the prospects with respect to both health and monetary consequences resulting from a decision taken by the physician, a fairly general approach to discuss diagnostic services is developed. The willingness to pay of the patient is taken to be measured by his compensating option price, evaluated with respect to the reference state without further diagnostic information. Of particular interest are conditions governing positivity of the patient benefit. Imposing additional restrictions upon individual preferences considerably simplifies the analysis by relying on a loss function. The final section discusses the role of the patient benefit as regards cost-benefit analysis of diagnostic services. If health insurance is available providing at least partial coverage, a positive willingness to pay of the patient net of diagnostic cost can be shown to give no clue as to whether utilization of a diagnostic service is beneficial to society in the sense of cost-benefit analysis. PMID- 7994326 TI - Shared 'features' in prices: income and price elasticities for health care expenditures. AB - The evidence found in most studies suggests a strong positive relationship between health care expenditure and gross domestic product. However, this evidence weakens with respect to the actual value of the income elasticity. There are two possible sources of these discrepancies, the use of arbitrary deflators and specification errors. We find that health PPP cannot be taken as a 'universal' price index. The problem is that its components do not move together. Nevertheless, we derive a 'universal' health price index from a dynamic system in which its components share both short and long run co-movements. The omission of relevant explanatory variables seems to be the main cause of the discrepancies. We confirm that there exists a strong positive relationship between per capita health care expenditure and per capita GDP. However we estimate a long run income elasticity at or around unity, although it is greater than unity for the countries with lower per capita income (Spain and Ireland). The results for income elasticity are the same regardless of whether health care expenditure is converted using the GDP PPP or the 'universal' health price index. The importance of non-income variables is also confirmed, in particular the relative price of health care. We find that relative price has a strong rationing effect on the quantity of health demanded and has no effect on the expenditures. PMID- 7994328 TI - [Metabolic aspects of intensive care in neonatology]. PMID- 7994327 TI - Measuring inequalities in health in the presence of multiple-category morbidity indicators. AB - This paper considers the problems which arise in seeking to measure socioeconomic inequalities in health when the health indicator is a categorical variable, such as self-assessed health. It shows that the standard approach--which involves dichotomizing the categorical variable--is unreliable. The degree of measured inequality is found to depend on the cut-off point chosen and the choice of cut off point to affect the conclusions one can reach about trends in or differences in health inequality. The paper goes on to propose an alternative approach which involves constructing a latent health variable and then measuring inequalities in this latent variable by means of a variant of the health concentration curve. PMID- 7994329 TI - [Jean-Francois Borel: discoverer of cyclosporin]. PMID- 7994330 TI - [Morphological abnormalities of the pituitary stalk of unknown cause in 4 cases of diabetes insipidus in children]. AB - BACKGROUND: Magnetic resonance imaging (MRI) is the best technique for studying hypothalamic and hypophyseal structures. CASE REPORTS: Four children aged 2 years 5 months to 8 years with idiopathic diabetes insipidus were studied. Their condition had been identified for 2-6 years. All the patients had undergone complete clinical, neurological and endocrinological investigations during the search for the cause of their diabetes insipidus. A CT scan was performed in one patient and MRI in all four; the investigations were repeated each 6 months for 4 years. RESULTS: The first examination showed complete lack of antidiuretic hormone (four patients) and growth hormone deficiency (two patients). An enlarged pituitary stalk was seen in three patients, one patient had a small anterior pituitary, and three patients gave no posterior pituitary hypersignal. Follow-up showed that three patients completely lacked of growth hormone. One was thyrotropin deficient, three had persistent enlarged pituitary stalks, three had sub-normal anterior pituitaries and all four patients produced no post-pituitary hypersignal. None of the patients developed signs of histiocytosis or germinoma. CONCLUSION: The finding of abnormal pituitary stalks by MRI raises the possibility that the apparently idiopathic diabetes insipidus is due to some type of infiltrating disease of the hypothalamus and pituitary. PMID- 7994331 TI - [Medium-chain acyl-CoA dehydrogenase deficiency: contribution of molecular biology]. AB - BACKGROUND: Medium-chain acyl-CoA dehydrogenase deficiency is the most frequent cause of defective congenital fatty acid oxidation. Its molecular characterization is now possible. Case n. 1. A girl, 15 month-old, was admitted because she suffered from fever and vomiting, requiring the administration of aspirin. One day later, she showed signs of drowsiness and hypotonia; her blood glucose concentration was 0.3 g/l. She was given intravenous glucose and this episode rapidly passed. Case n. 2. A boy, brother of the preceding patient, was routinely investigated; he was never symptomatic. Case n. 3. A boy, sibling of the two preceding children, was admitted at the age of 18 months because he had gone into a coma during a febrile episode. His blood glucose concentration was 0.15 g/l. This episode was rapidly resolved by a glucose infusion. His fasting blood concentrations of glucose, non esterified fatty acids. beta hydroxybutyrate, lactate and pyruvate were normal as were his blood carnitine and ammonia, but he showed elevated urinary excretion of dicarboxylic acids. METHODS: Genomic DNA was extracted from peripheral leukocytes of the three sibs and their parents. The A-->G mutation at nucleotide 985 of the MCAD gene was detected by amplification and creation of a restriction site (ACRS). The implicated segment of this gene was amplified by PCR. RESULTS: ACRS showed that the symptomatic children were homozygous for the A-->G mutation, whereas their parents were heterozygous. The third asymptomatic child did not carry the mutation. CONCLUSIONS: Molecular biology techniques are appropriate for diagnosing this potentially lethal disease and their use for screening is important for disease prevention. PMID- 7994332 TI - [Acute respiratory infections in pediatric hospital at Bobo-Dioulasso (Burkina Faso)]. AB - BACKGROUND: Acute lower respiratory tract infections are the primary cause of morbidity in developing countries. POPULATION AND METHODS: Six hundred and sixty seven children (379 boys, 288 girls, aged 0-30 months) admitted for lower respiratory tract infections from January 1990 to March 1991 were included in the study. Immediate medical history was collected from the mother. The weight, height, temperature and clinical manifestations, plus the results of chest X rays, parasitologic and bacteriological examination of stools, and blood smear for malaria were recorded for each patient. Sero-immunologic study for HIV infection of 473 of the patients aged 12-36 months and their mothers also took part in a sero-immunological study for HIV infection. RESULTS: Lower respiratory tract infections were the second major cause of admission (16.8%) after malaria (28.7%). Infections peaked between 6 and 11 months of age (29.5%). The main diseases were pneumonia and bronchial pneumonia (54%) followed by bronchiolitis (21.7%). Almost half the patients were admitted during the hot, dry season. Two hundred and eighty seven patients (43.4%) were referred only after they had been suffering from the disease for 3 to 9 days, partly explaining the high level of mortality. One hundred and twenty one patients (20.9%) died; the main cause of death was staphylococcal pneumonia (57.9%), followed by pneumonia and bronchial pneumonia (29.3%). Some criteria for severity could be identified, based on pulmonary signs and symptoms and associated manifestations (dehydration, malnutrition, convulsions, anemia). Twenty two patients were positive for HIV-1 infection. CONCLUSIONS: This study confirms that acute lower respiratory tract infections remain a public health problem. Early diagnosis and treatment are necessary to reduce mortality. PMID- 7994333 TI - [Convulsions and neonatal hypoparathyroidism revealing maternal hyperparathyroidism]. AB - BACKGROUND: Severe prolonged hypocalcemia may occur in neonates whose parathyroid hormone production has been blocked by maternal hyperparathyroidism. This report describes such a case. CASE REPORT: A 7 day-old girl was admitted suffering from dyspnea and repeated convulsions that had continued for 2 days. Her birthweight was 3,500 g and her height 50 cm. Her mother had been given an iron preparation and calcium during pregnancy. Clinical examination of the newborn at birth revealed a cleft palate and micrognathia. The baby had been given milk-formula plus ergocalciferol, 1,200 IU/day. At admission, the baby was hypotonic. Her serum total calcium was 1.27 mmol/l; total proteins 61 g/l; ionized calcium 1.1 mmol/l; phosphorus 2.14 mmol/l; intact PTH 21 pg/ml (N = 10-65) and 25(OH)D 8 ng/ml (N = 8-30). She was given intravenous calcium gluconate (1 g/m2/d), diazepam (0.5 mg/kg) rectally, intravenous phenobarbital (20 mg/kg) but intravenous phenytoin was needed to stop clinical and electrical seizures. Her blood calcium was normalized 5 days later. Her mother, who was clinically normal, had: total serum calcium: 2.72 and 2.77 mmol/l; total proteins: 71 g/l; phosphorus: 0.85 mmol/l; intact PTH: 73 pg/ml; 25(OH)D: 6 ng/ml; Ultrasonography showed an adenoma of the right parathyroid. Further studies on the baby showed no signs of Di George syndrome. CONCLUSION: Neonatal hypocalcemia always requires investigation of both the infant and mother. Measurements of vitamin D metabolites and intact PTH are required to recognize maternal hyperparathyroidism. PMID- 7994334 TI - [Acute urine retention: a rare mode of revelation of cervico-dorsal syringomyelia caused by cyproheptadine]. AB - BACKGROUND: Syringomyelia is rare in children aged less than 10 years, and bladder dysfunction is an unlikely first manifestation. This report describes a case of repeated episodes of acute urinary retention in a young girl revealing syringomyelia and Arnold-Chiari malformation. CASE REPORT: A 2.5 year-old girl was admitted because she was suffering from acute urinary retention. Her poor appetite had been treated with cyproheptadine, a histamine type I blocking drug. Clinical investigation revealed no local cause for this bladder dysfunction except moderate spasticity of the legs. Cystography showed no vesicoureteral reflux. Because the episodes of urinary retention recurred each day, magnetic resonance imaging (MRI) was performed; this showed the typical features of syringomyelia extending from C5 to T11 plus Arnold-Chiari malformation. The cyproheptadine was discontinued and the urinary retention disappeared. CONCLUSION: Cyproheptadine may have revealed latent neurogenic bladder in this case, although urodynamic studies, performed 3 months later, detected no bladder dysfunction. PMID- 7994335 TI - [Septicemia due to Streptococcus milleri with pulmonary complications]. AB - BACKGROUND: Streptococcus milleri can occasionally cause serious septicemia, that is often complicated by abscesses, particularly pulmonary. CASE REPORT: A 12.5 year-old boy was admitted because he had suffered from fever for 6 days. He also had headache, diffuse abdominal pain, chills and a cough. Laboratory investigations showed leukocytes: 9,300/mm3 (PMN: 6,700/mm3; lymphocytes: 1,400/mm3; monocytes: 1,200/mm3); hemoglobin: 12.5 g/dl; platelets: 106,000/mm3; sedimentation rate: 120 mm at 1 hour; blood fibrinogen: 5.6 g/l and C-reactive protein: 193 mg/l. His chest X-rays was normal. Four blood cultures showed Streptococcus milleri. The patient was given amoxicillin (150 mg/kg/d) plus gentamicin (3 mg/kg/d). Two foci of dental infection were found and treated by tooth extraction. Blood cultures remained positive 2, 3 and 6 days after onset of treatment and a second chest X-rays and CT scan showed several bilateral pulmonary abscesses. Cardiac ultrasonographs showed no valvular vegetations. The patient was then given ceftriaxone (100 mg/kg/d) plus rifampicin (20 mg/kg/d) and netilmicin (6 mg/kg/d). Blood culture was negative two days later, but the fever persisted and ceftriaxone was then successfully replaced by vancomycin (40 mg/kg/d) for three weeks. CONCLUSION: There are several reasons for the apparent resistance to treatment of this potentially severe infection; they are discussed by the authors. PMID- 7994336 TI - [Physiopathological approach and antenatal diagnosis of diabetes mellitus insulin resistant: apropos of a case with leprechaunism]. AB - BACKGROUND: Leprechaunism is characterized by severe intrauterine growth retardation, elfin-like face, relatively large hands, feet and genitalia and abnormal skin with hypertrichosis, acanthosis nigricans and low subcutaneous fat. The insulin receptors have multiple defects. CASE REPORT: A boy was born after cesarean section at the 35th week of gestation because of intrauterine growth retardation: weight: 930 g; height: 36 cm; head circumference: 27 cm. He had trigonocephaly, coarse features and hyperkeratosis. Ultrasonography confirmed the presence of a ventricular septal defect detected during pregnancy. Hyperglucosemia (3 g/l) was associated with insulinemia above 350 mU/l; his C peptide concentration was above 20 ng/ml. The patient was given intravenous insulin, up to 2,500 U/kg/d. He died at the age of 95 days, weighing 1500 g, with persistent hyperglucosemia and cholestasis. Postmortem examination showed adrenal and thymus hypoplasia and hyperplasia of pancreatic islet cells. Molecular biology studies showed that this patient was heterozygotic for two mutations, one in exon 20 inherited from his father, the other in exon 18 inherited from his mother; both mutations are associated with tyrosine-kinase activity of the insulin receptor. These results will be used for antenatal diagnosis in any future pregnancy. CONCLUSION: Molecular biology can indicate specific defects in the insulin receptor. It may also allow antenatal diagnosis in some families. PMID- 7994337 TI - [Measurement of renal function in children]. AB - Assessment of renal function in children raises several difficulties concerning technical and analytical aspects. Renal function parameters are influenced by both age and renal failure. Inulin clearance is the standard method to measure glomerular filtration rate, but it cannot be routinely used. Among other methods, plasma creatinine determination is not reliable to evaluate the level of renal function or to follow the course of renal diseases. Creatinine clearance estimated from calculations such as Schwartz formula does not provide an accurate estimation of the glomerular filtration rate. More precise estimate can be obtained from endogenous creatinine clearance, providing that the measurement is performed accurately. In this paper the authors review these factors and report personal data obtained from 500 children who underwent renal function investigation. PMID- 7994338 TI - [Megaloblastic anemia in children]. AB - Megaloblastic anemia in children is mainly due to folic acid or vitamin B12 deficiencies. However dosages of these two vitamins must be performed before any vitamin supplementation or blood transfusions are given in order to establish precisely the etiologic diagnosis. A disorder in the metabolism of these vitamins must be considered in any infants in whom the onset of neurological abnormalities is associated with the characteristic hematological abnormalities. Imerslund's syndrome is a specific vitamin B12 malabsorption defect that warrants consideration as it is easy to recognize on the basis of the association of megaloblastic anemia and proteinuria. A possible drug-induced etiology must also be looked for. In the absence of vitamin deficiency, several rare etiologies must be considered. A macrocytosis, occasionally with megaloblastosis reflecting an abnormal erythropoiesis, may accompany an hemopathy, eventually malignant. PMID- 7994339 TI - [Children in parental separation. Review of the literature]. AB - The authors present a synthesis of the studies published in the literature since 1980 concerning the psychological consequences of parental separation on children. The risk of psychological disturbances varies according to the age and the sex of the child, and to the different parental attitudes. Pediatricians have an important role in preventing psychological consequences of parental separation on children by giving information to the parents and helping the children to understand and accept the event. In addition early recognition of psychological disturbances is important in order to offer a specialized support to the child. PMID- 7994340 TI - [Antibiotic therapy of appendicular peritonitis in children]. PMID- 7994341 TI - [Lupus erythematosus disseminatus and vaccination against hepatitis B virus]. PMID- 7994342 TI - [Group B streptococcal infection in the neonatal period]. PMID- 7994343 TI - [Urinary tract infection due to Enterococcus, not detected by urinary strip test]. PMID- 7994344 TI - [For early prevention of osteopenia in anorexia nervosa]. PMID- 7994345 TI - [The weak link. Apropos of safety during labor and delivery]. PMID- 7994346 TI - [Agyria-pachygyria and pachygyria in children. Contribution of imaging]. AB - BACKGROUND: Lissencephaly (agyria-pachygyria) is a defect in migration of cerebral neurons resulting in failure of cortical gyri to develop. Progress in imaging techniques improves its diagnosis. POPULATION AND METHODS: The files of 17 patients (ten boys and seven girls), aged 7 months to 16 years, were retrospectively studied. The clinical picture consisted of mental retardation (17 patients), seizures (eight patients), facial dysmorphia (seven patients), axial hypotonia (four patients). CT scan was performed in 16 cases and MRI with T1 and T2 weighted images in all 17. RESULTS: The CT scan identified pachygyria in 12 cases. Cerebral calcifications were seen in four cases. MRI detected typical changes in all 17 cases: thickened cortex and gyri, loss of cortical white matter interdigitations, lack of operculisation of the sylvian fissure. Pachygyria was generalized (six patients) or localized (11 patients). Associated abnormalities were dysgenesis of corpus callosum in three patients, cerebellar hypoplasia in one, deep grey matter heterotopia in one; hypersignal of the white matter was identified on T2 weighted images in five patients. CONCLUSION: MR imaging permits precise analysis of abnormalities secondary to a defect in neuronal migration. PMID- 7994347 TI - [Neonatal hyperglycemia and diabetes mellitus]. AB - BACKGROUND: Hyperglycemia in the neonate may be permanent or more frequently transient. Its treatment is still debated. PATIENTS AND METHODS: The files of 19 infants with hyperglycemia were retrospectively analysed. Their birth-weights were more than 900 g and their gestational ages more than 27 weeks. Plasma glucose, insulin, C-peptide, islet-cell and insulin autoantibodies were measured in each patient. RESULTS: Blood glucose ranged from 1.2 to 10 g/l (mean: 5.05 +/- 1.0), between the second hour and the 60th day of life. Four infants presented with permanent neonatal diabetes mellitus: they were small for gestational age. Hyperglycemia was noted from the first day of life. C-peptide levels were less than 0.1 pmol/ml and autoantibodies were absent. Two sibs had hypothyroidism, one patient had unclassifiable chronic diarrhea plus renal disease, the fourth patient had ventricular septal defect. The 15 other patients presented with a transient hyperglycemia that appeared lately (6.1 +/- 3.4 day of life). Hyperglycemia was induced by glucose infusion in five patients, by potentially hyperglycemic drugs in five others. C-peptide levels ranged from 0.01 to 0.76 pmol/ml (mean 0.29 +/- 0.11). One patient and his mother had insulin antibodies. Another patient had congenital heart abnormalities. Hyperglycemia required insulin therapy in 17 cases (four with permanent and 13 with transient hyperglycemia). CONCLUSION: There are no clinical or biological features permitting foresee the duration of neonatal hyperglycemia. Each patient with birth-weight below 2,500 g should be given insulin when glucosemia remains above 1.3 g/l and his weight does not increase. PMID- 7994348 TI - [Neonatal trismus]. AB - BACKGROUND: Trismus is caused by sustained contraction of the jaw-closing muscles. It is rare in the neonate and can be a part of developmental defects. PATIENTS AND METHODS: Twenty-four neonates, aged 1 to 12 days, were admitted from 1980 to 1992 because they suffered from trismus. All of them had severe difficulties of sucking and/or swallowing, some (12/24) had repeated episodes of apnoea requiring tracheotomy. Specialized investigations included transcutaneous PO2 and PCO2 monitoring, polygraphic recordings during sleep, 24-hour Holter monitoring, ocular compression test, barium swallow, manometry and 24-hour pH monitoring of the distal esophagus, electromyography of muscles involved in swallowing and several imaging techniques. RESULTS: Twenty-one patients had anomalies of the facies and brain stem dysfunctions. They were classified as Robin sequence (14 patients) with (five patients) or without (nine patients) micrognathia, cleft palate and glossoptosis, as Hanhart syndrome (four patients) and Moebius syndrome (three patients). The last three patients had arthrogryposis (two patients) and Stuve-Wiedeman syndrome. Twenty-two of 24 patients had severe gastroesophageal reflux, 15 of 20 had increased vagal reactivity and five of 24 had anomalies of the central nervous system. Eight patients died during the first year of life. CONCLUSION: Neonatal trismus is a poor prognostic sign, requiring specialized investigations and frequently resuscitation techniques. PMID- 7994349 TI - [Acute hepatopathy compatible with Reye's syndrome in 3 children treated by chemotherapy]. AB - BACKGROUND: Chemotherapy for malignant diseases sometimes leads to hepatic toxicity. Reye's syndrome has not been described in such a situation. CASE REPORTS: Three children, 4, 5 and 6 years-old, were treated for lymphoma or acute lymphoblastic leukemia. They were given polychemotherapy including drugs that were not potentially hepatotoxic. During remission, they suddenly developed manifestations such as neurologic disturbances, hepatomegaly, increased activity of liver enzymes, and microvesicular steatosis. These disturbances were consistent with the diagnostic criteria for Reye's syndrome recommended by the Centers for Disease Control. Factors such as viral infection, salicylate administration, primary metabolic disorder were not present. One child died and the other two recovered completely. CONCLUSION: Patients given chemotherapy, even though the relationship between them remains to be determined, may develop manifestations compatible with a diagnosis of Reye's syndrome. PMID- 7994350 TI - [Hashimoto-Pritzker self-healing reticulohistiocytosis and congenital histiocytosis]. AB - BACKGROUND: Congenital histiocytosis is divided into four entities differing in their clinical and histological features and prognosis. Early, accurate diagnosis is essential for treatment. CASE REPORT: Seven cutaneous nodules were seen in a male neonate. One of these nodules was biopsied on the 7th day of life; it showed the typical findings of Hashimoto-Pritzker reticulohistiocytosis by optical and electron microscopy using immunological markers. The nodules spontaneously disappeared after a few months. CONCLUSIONS: Congenital forms of histiocytosis must be accurately characterized. Hashimoto-Pritzker reticulohistiocytosis is a benign and self-healing disease restricted to the skin, while the Letterer-Siwe disease has a completely different course and treatment. PMID- 7994351 TI - [Constitutional translocation t(1;6) and Burkitt's lymphoma]. AB - BACKGROUND: The relationship between constitutional chromosome aberrations and a predisposition to malignancy has already been established. CASE REPORT: A 4 year old boy was admitted suffering from abdominal mass. Biopsies of the tumor and bone marrow showed a stage IV Burkitt's lymphoma. Karyotype showed a constitutional t(1;6)(p36;q22) in initial bone marrow samples and peripheral lymphocytes. No classic Burkitt's type translocation was demonstrated in the malignant bone marrow cells. CONCLUSION: Our case is similar to four other reported cases. The break-points 1p36 and 6q22 seem to be involved in several malignant tumors, especially lymphomas. PMID- 7994352 TI - [Idiopathic pulmonary hemosiderosis, celiac disease and cardiomyopathy]. AB - BACKGROUND--Idiopathic pulmonary hemosiderosis (IPH), a rare and possibly immune disease, is sometimes associated with coeliac disease and myocardiopathy. CASE REPORTS: CASE NO 1--A 2 year-old boy with IPH was investigated because he suffered from frequent, soft stools. Small bowel biopsy showed partial villous atrophy. Circulating gliadin antibodies were present. The patient was placed on a gluten-free diet. CASE NO 2--An 8 year-old girl was admitted because she suffered from severe anemia (Hb: 4 g/100 ml). She was found to have IPH and myocardiopathy. She had no manifestation, but a systematic search for coeliac disease was positive (total villous atrophy; presence of circulating gliadin and alveolar basement membrane antibodies). The patient was placed on a gluten-free diet, prednisone and diuretics, but she died during a relapse 2 months later. CONCLUSION--It is worthwhile checking for coeliac disease in all patients with IPH. The presence of myocardiopathy is a negative prognosis. PMID- 7994353 TI - [Pre- or neonatal corticotherapy: what are the long-term consequences?]. AB - This paper is a literature overview on the potential long-term side effects of steroid therapy in the prenatal and neonatal period. Incomplete and transient suppression of adrenal function without growth impairment has been reported in prolonged treatment with steroids for bronchopulmonary dysplasia. There seems to be no secondary chronic immune dysfunction. There is evidence for deleterious effects on lung and brain development in experimental animals. In human preterm neonates, no pulmonary and cerebral secondary effects were observed after short prenatal steroid courses, but it is as yet uncertain whether this applies also to prolonged steroid therapy which requires further long-term investigations, including school performance. PMID- 7994354 TI - [Urological treatment of urolithiasis in children]. AB - Endo-urological techniques and extracorporeal shock waves lithotripsy (ESWL) have dramatically improved the management of urolithiasis in children. ESWL has been shown to be safe and effective, achieving a stone clearance rate up to 85% with minimal short-term morbidity, and this non-invasive method has become the first line treatment for most upper urinary tract calculi in children. However, it long term effects on kidney function and growth remain unknown, and its repeated use should therefore be restricted. Endo-urological techniques, mainly percutaneous procedures and ureteroscopy, and surgical procedures, are only indicated for large multiple stones, or secondary stones needing simultaneous treatment of an underlying uropathy. PMID- 7994355 TI - [Depression in children. Etiological, clinical and therapeutical aspects]. AB - Although the concept of child depression is today well admitted, the diagnosis of childhood depression remains difficult due to the variety of its symptoms, many of them being non specific, and the frequency of masked depression. For each period of child development, ie: infancy, early childhood, late childhood and adolescence, depression has particular clinical characteristics which are important to be known for its early recognition. Depression in a child frequently appears to result from the conjunction of a constitutional predisposing ground, one or several losses, and an inappropriate parental response. One must be concerned about the major risk of deleterious effects on psychoaffective, intellectual and somatic development of neglected depression, so that its prevention, early recognition, and treatment are mandatory. According to the cases, treatment requires individual or familial psychotherapy and chemiotherapy, and in particular cases care in a medico-educative establishment. PMID- 7994356 TI - [Radiological case of the month. Mesenchymal hamartoma of the chest wall in a newborn infant]. PMID- 7994357 TI - [Vitamin D and breast feeding]. PMID- 7994358 TI - [Congenital Hashimoto-Pritzker histiocytosis]. PMID- 7994359 TI - [Effect of E coli or Erwinia asparaginase and corticotherapy on fibrinogen concentration in induction of acute lymphoblastic leukemia in children]. PMID- 7994361 TI - Blood substitutes: modified hemoglobin. Vth International Symposium on Blood Substitutes. San Diego, California, March 17-20, 1993. Proceedings. PMID- 7994360 TI - Increased vascular resistance with hemoglobin-based oxygen carriers. AB - PURPOSE: To compare the effects of resuscitation with hemoglobin-based oxygen carriers and conventional resuscitation fluids on hemodynamics, oxygen transport, and oxygen consumption in an animal model of the use of these fluids in the treatment of hemorrhagic shock. PROTOCOL: Twenty-eight immature swine were surgically prepared, allowed to recover five days, water deprived for 48 hours, hemorrhaged of 25 ml/kg over one hour, resuscitated promptly with 1) Ringer's lactate, 75 ml/kg, 2) 7% albumin in Ringer's acetate, 25 ml/kg, 3) 9% unmodified hemoglobin in Ringer's acetate, 25 ml/kg, or 4) 9% alpha alpha-crosslinked hemoglobin in Ringer's acetate, 25 ml/kg, and observed with three hours of hemodynamic and oxygen transport measurements. RESULTS: Systemic and pulmonary vascular resistance were increased in hemoglobin-treated animals to more than twice the levels seen in crystalloid- or colloid-treated controls. Oxygen consumption and the rate of correction of lactic acidosis were not increased in hemoglobin-treated animals. CONCLUSIONS: Increased vascular resistance limits the oxygen transport benefit of cell-free-hemoglobin-based oxygen carriers. Cell-free hemoglobin-induced increases in vascular resistance may place animals' hearts on an unfavorable portion of the Frank-Starling curve as well as complicate further medical treatment by reducing the animals' tolerance to increases in blood viscosity. PMID- 7994362 TI - Redox reactivity of modified hemoglobins with hydrogen peroxide and nitric oxide: toxicological implications. AB - The rapid unloading of oxygen to tissue and the prevention of subunit dissociation have been the main concerns in the search for an effective hemoglobin-based red cell substitute. The presence of redox active iron however, raises some questions about its potential to enter into reactions that mediate the formation of cytotoxic oxygen free radicals. We tested the propensity of modified hemoglobins to undergo oxidative damage by peroxide (H2O2). We found differences in their susceptibility to oxidative modification and in their ability to form the highly cytotoxic ferryl species. This protein-associated oxidant may be a physiologically important contributor to reperfusion injury. Another potential mechanism of toxicity involves the reaction of cell-free hemoglobin with endothelium derived nitric oxide (NO). Marked hypertensive responses in intact animals infused with some of these hemoglobins were reported. Cell-free hemoglobin has the potential to bind the endothelial generated NO yielding methemoglobin and nitrate, an extremely rapid reaction in vivo. We describe subsequent redox reactions between NO and methemoglobin which may further deplete NO as a biological transducer, leading to greater effects on the extent of endothelial-dependent responses. The consequences of a potential linkage between oxidative toxicity of cell-free hemoglobin and its interaction with NO is addressed. PMID- 7994363 TI - Toxicity of hemoglobin solutions: hemoglobin is a lipopolysaccharide (LPS) binding protein which enhances LPS biological activity. AB - Administration of alpha alpha-crosslinked stroma-free hemoglobin (SFH) as a cell free resuscitation fluid is associated with multiple organ toxicities. Many of these toxicities are characteristic of the pathophysiological effects of bacterial endotoxins (lipopolysaccharide, LPS). To better understand the potential role of LPS in the observed in vivo toxicities of SFH, we examined mixtures of SFH and E. coli LPS for evidence of LPS-SFH complex formation. LPS SFH complexes were demonstrated by three techniques: ultrafiltration through 300 kDa cut-off membranes, which distinguished LPS in complexes (87-89% < 300 kDa) from LPS alone (90% > 300 kDa); density centrifugation through 5% sucrose, which distinguished denser LPS alone from LPS-SFH complexes; and precipitation by 67% ethanol, which demonstrated 2-3 fold increased precipitability of complexes compared to SFH alone. Interaction of LPS with SFH was also associated with markedly increased biological activity of LPS, as manifested by enhancement of LPS activation of Limulus amebocyte lysate (LAL), increased release of human mononuclear cell tissue factor, and enhanced production of cultured human endothelial cell tissue factor. These results demonstrated that hemoglobin can serve as an endotoxin binding protein, and that this interaction results in the alteration of several LPS physical characteristics and enhancement of LPS biological activities. PMID- 7994364 TI - Assessment of hemoglobin-dependent neurotoxicity: alpha-alpha crosslinked hemoglobin. AB - Adult human hemoglobin A0 (HbA0) has been shown to be neurotoxic, and we wish to report on similar studies conducted using a modified hemoglobin, which has been crosslinked between the alpha subunits (alpha-alpha Hb). Cortical cell cultures were prepared from fetal Swiss-Webster mice at 15-16 days gestation. Mature cultures (days in vitro, 12-16) were exposed to alpha-alpha Hb in a defined medium for 24-48 hours at 37 degrees C. Low micromolar amounts of alpha-alpha Hb were neurotoxic in a concentration-dependent fashion. This toxicity was attenuated by the antioxidants Trolox and U-74500A and by the iron chelator deferoxamine. The hemoglobin-binding protein, haptoglobin, also completely blocked alpha-alpha Hb-dependent neurotoxicity. The latter result was unexpected because complex formation between alpha-alpha Hb and haptoglobin was not detected using assays of haptoglobin fluorescence and hemoglobin peroxidase activity. PMID- 7994365 TI - Cross-linking hemoglobin by design: lessons from using molecular clamps. AB - The development of a red cell substitute by chemical modification of hemoglobin has been approached as a systematic, iterative process. Acyl phosphate methyl esters were designed as anionic electrophiles to permit selective acylation of amino groups in the cationic site of hemoglobin which binds polyanions. Kinetic studies with systematically substituted acyl phosphates and amines show that the reaction is controlled by a reversible addition step followed by an irreversible elimination step. Acyl phosphate methyl esters which are derivatives of rigid dicarboxylic acids introduce cross-links in human hemoglobin between amino groups in the beta subunits (epsilon-NH2-Lys-82, alpha-NH2-Val-1) and permit correlation of oxygen binding properties with cross-link structure. The data suggest that the cross-link maintains cooperativity while reducing overall oxygen affinity by lowering the affinity of the R form for oxygen rather than by perturbing the R,T equilibrium of native hemoglobin. Materials produced from deoxyhemoglobin with a cross-link between positions 1 and 82 of the two beta units have appropriate oxygen affinity for red cell substitutes. The use of a trifunctional cross linker, trimesyl tris(methyl phosphate) selectively produces hemoglobin with the desired 1-82 connection in good yield. The reagent is readily prepared and the properties of this chemically modified hemoglobin are suitable for trial as a red cell substitute, closely resembling those of optimized materials produced by recombinant technology. Further work is producing new chemicals and providing structural information. PMID- 7994366 TI - Genetic engineering of myoglobin as a simple prototype for hemoglobin-based blood substitutes. AB - Site-directed mutagenesis has been used to examine the structural and functional roles of distal pocket residues in regulating O2 affinity, CO binding, rates of association and dissociation, autooxidation, and hemin loss in mammalian myoglobins and human hemoglobin. In myoglobin, His-E7 inhibits CO binding by requiring displacement of distal pocket water. In the case of O2 binding, this displacement is compensated by a strong hydrogen bond between the bound ligand and the imidazole side chain. The isopropyl side chain Val-E11 also sterically restricts CO binding. The rates of ligand binding are regulated by distal pocket water displacement, steric restrictions near the iron atom, and an outer more global protein barrier. Autooxidation occurs by two mechanisms, direct dissociation of HO2 and bimolecular reaction of external O2 with unliganded heme. Both processes are inhibited markedly by hydrogen bonding interactions with His E7. Double mutants have been constructed to decrease oxygen affinity, but still prevent oxidation. The apoprotein of His-E7-->Tyr myoglobin has been used to extract hemin from other myoglobins and hemoglobin, causing a brown to green color change. This assay has been used to show that polar interactions between residues CD3, E7, E10, F7, and the porphyrin propionates inhibit hemin dissociation markedly. PMID- 7994367 TI - A comparison of rates of heme exchange: site-specifically cross-linked versus polymerized human hemoglobins. AB - The stability of the heme-globin interaction of chemically modified human hemoglobin (Hb) was tested by measuring rates of heme loss from methemoglobin. Heme transfer from methemoglobin to human serum albumin was measured by rapid scanning spectrophotometry, and the resulting absorption matrices were analyzed by singular value decomposition. Unmodified human HbA0, hemoglobin cross-linked between beta subunits with either 2-nor-2-formylpyridoxal 5'-phosphate or 3,5 (dibromosalicyl)fumarate (DBBF), hemoglobin cross-linked between alpha subunits with DBBF, and pyridoxalated hemoglobin polymerized with either glycolaldehyde or glutaraldehyde were tested. Initial rates were evaluated by fitting the time courses to a biexponential equation using a matrix least squares curve-fitting algorithm. Reaction rates fell into two classes: (1) HbA0 and the site specifically cross-linked hemoglobins, with biphasic rates of heme loss of 0.02 and 0.004 min-1, and (2) polymerized hemoglobins, with 10-20-fold higher rates at 0.5 and 0.03 min-1. The total fitted amplitudes of the reaction depended upon the specific modification: beta beta-cross-linked Hbs < alpha alpha-cross-linked Hb approximately glycolaldehyde polymerized Hb < glutaraldehyde polymerized Hb < HbA0. PMID- 7994368 TI - Initial clinical experience with a rationally designed, genetically engineered recombinant human hemoglobin. PMID- 7994369 TI - Stabilized hemoglobin vesicles. AB - The Hb-vesicles which encapsulate the purified and concentrated Hb more than 40 g/dl with a uni- or bi-lamellar membrane are prepared by extruding the dispersion of mixed lipids through membrane filters (final pore size: 0.2 micron phi). They transport large amount of oxygen with satisfying rheological properties such as oncotic pressure and solution viscosity. Oxygen affinity of the Hb-vesicles is adjusted so as to exceed the ability of oxygen transport of human blood by coencapsulating allosteric effectors in the Hb-vesicles. The solution is sterilizable because of the diameter of Hb vesicles less than 0.2 micron phi. The Hb-vesicles are stabilized by using polyphospholipid or glycolipid as membrane components. No change in oxygen affinity and particle size was confirmed during long time storage at 4 degrees C. The stabilized Hb-vesicles can also be stored as frozen or dried state. The dried Hb-vesicles are regenerated by simply adding pure water. Simple in vitro test indicates that Hb-vesicles have the reduced inhibitory action of Hb to the EDRF-mediated vasorelaxation. PMID- 7994370 TI - Cross linking encapsulated hemoglobin with solid phase supports: lipid enveloped hemoglobin adsorbed to surface modified ceramic particles exhibit physiological oxygen lability. AB - To reduce hemoglobin toxicity, a cross linking agent is generally used. To preserve hemoglobin function, an allosteric modifier is generally used. Historically, the use of one has precluded the use of the other. A potential solution to this problem was investigated. Hemoglobin AO was adsorbed irreversibly to carbohydrate coated nanosized diamond particles and then encapsulated in a standard mixture of phospholipids. Endotoxin free preparations with concentrations of bound hemoglobin near 10 g/dl were achieved with as little as 0.1 g/dl of free hemoglobin and remained stable over a 48 hour period. By transmission electron microscopy these particles appeared roughly spherical and measured approximately 75 nanometers well below that of alveolar capillary vessels. In shallow pH gradients, liquid electrophoresis demonstrated that such constructs exhibit Bohr effect behavior by the induction of a dramatic surface charge inversion at around pH 6.8. To evaluate oxygen lability, oxygen saturation trials were conducted in isosmolar physiological salts. Normal sigmoidal binding behavior of O2 over a typical pO2 gradient could be modulated by systemic levels of pyridoxyl-5-phosphate. Constructs with a P50 as low as 12 mm Hg could be increased to 37 mm Hg with the allosteric effector. Viscosity and bio distribution studies are to follow. The use of solid phase nanocrystalline supports to cross link hemoglobin may reduce the toxicity of free hemoglobin while still enabling the use of allosteric modifiers. PMID- 7994371 TI - Efficacy, physical properties and pharmacokinetics of sterically-stabilized liposome-encapsulated hemoglobin. AB - We recently reported that hemoglobin (Hb) encapsulated in liposomes (LEH) containing phosphatidyl-inositol (PI) was efficacious in rats. However, liposomes containing PI may temporarily compromise mononuclear phagocytic system (MPS) function. The objective of this study was then to determine whether a polyethylene oxide derivative of phosphatidyl ethanolamine (PEG-PE) would serve as an acceptable substitute for PI in our LEH formulation. In this study we compare the physical properties, pharmacokinetics and efficacy in life support obtained for Hb encapsulated with either PI or PEG-PE phospholipids. Both liposome compositions contained the same matrix lipids, egg derived phosphatidyl choline (PC) and cholesterol, were of similar size and contained the same amount of encapsulated Hb. The liposomes differed only in their phospholipid component, one containing 5 mol% PI and the other an equal amount of the sterically stabilizing lipid PEG-PE. The physical characteristics of the PI and PEG-PE compositions were remarkably similar: only small amounts of Met-Hb were generated during processing and following 1 month frozen storage, oxygen affinity and cooperativity and steady shear viscosity values for 30% by volume suspensions (in isotonic/isooncotic saline containing albumin) were near the normal values expected for whole blood, incubation in plasma at 37 degrees C resulted in only small amounts of Hb release and shear had very little impact on Hb leakage. Circulation half-lives following 50% isovolemic exchange-transfusion in rats were also similar, about 15-20 hours for either formation. Animals survived following 97% isovolemic exchange-transfusion of both compositions, confirming the efficacy of each. PMID- 7994372 TI - Effect of neo red cells on hemodynamics and blood gas transport in canine hemorrhagic shock and its safety for vital organs. AB - The purpose of this study was to evaluate the effects of liposome encapsulated hemoglobin named "Neo Red Cells (NRC)" on canine hemorrhagic shock model and its safety for the vital organs in a whole blood exchange model. HEMORRHAGIC SHOCK: Nine adult mongrel dogs were used. Under mechanical ventilation inhaling room air, blood was withdrawn via an artery at a rate of 40 ml/min in order to induce hemorrhagic shock (systolic pressure below 60 mm Hg) and then NRC was transfused. For each animal, three to five cycles of bloodletting and NRC transfusion were performed. After blood exchange, total peripheral resistance index (TPRI) decreased and cardiac index (CI) increased. These changes were more marked in the high exchange group (exchange rate over 88%; five animals) than in the low exchange group (less than 88%; four animals), indicating that the low viscosity NRC reduced the load on the circulatory system. The A-V difference in oxygen content per lg hemoglobin was greater after blood exchange, indicating that oxygen binding capacity of NRC is higher than that of red blood cells. WHOLE BLOOD EXCHANGE: Five beagles were used for the blood exchange. The blood was withdrawn from an artery at a rate of 15 ml/min and NRC was infused at the same time. A dog whose blood was exchanged with hydroxyethylstarch instead of NRC died within 15 hours after blood exchange. Three dogs whose blood was exchanged with NRC (exchange rate was from 82 to 90%) have been living over a year without any side effects. A dog sacrificed on the 15th postoperative day for autopsy, microscopically showed no side effects in vital organs. We conclude that NRC is more suitable than natural blood for treatment of hemorrhagic shock and safe for vital organs. PMID- 7994374 TI - Cytokines and PAF release from human monocytes and macrophages: effect of hemoglobin and contaminants. AB - Monocytes [M] were isolated from venous blood of healthy volunteers and activated macrophage-leukocytes (Mo-L] were obtained from peritoneal fluid of patients with mild endometriosis. The M were incubated with pyrogen free CELLGRO culture medium [Control], and with 0.2 mM of [A] unmodified bovine hemoglobin (UHb), [B] Hb crosslinked to form polymers with M.W. < 400 kDa (LMWHb), [C] Hb crosslinked to form large polymers (< 1,020 kDa) (HMWHb), and Mo-L additionally with [D] UHb contaminated with endotoxin (Hb+E) (2.5 EU/mL), and [E] UHb contaminated with phospholipids (Hb+PLs). The Mo-L medium of incubation was tested for TNF alpha, IL-1 alpha, IL-6, GM-CSF and PAF after 6 and 24 hours, but M for TNF alpha and GM CSF at 12, 24 and 36 hours. Mo-L were found more responsive than M colonies. The strongest reaction of Mo-L was to Hb+E, which produced levels of cytokines and PAF higher than Controls (p < 0.001). Hb+PLs induced smaller increases of TNF and IL-6, and a decrease in the levels of IL-1 and GM-CSF. However, the release of PAF was much greater with this Hb than with Hb+E. UHb caused an increase in TNF, as compared to control (p < 0.01). LMWHb generated a similar increase in TNF, but also a decrease in IL-1. Both polymerized Hb forms inhibited expression of GM CSF. HMWHb induced high levels of TNF, IL-1 and PAF. UHb, LMWHb and HMWHb significantly increase levels of TNF in M cultures after 36 hours of incubation. PMID- 7994373 TI - Enhanced oxidation of bis(3,5-dibromosalicyl) fumarate alpha-alpha cross linked hemoglobin by free radicals generated by xanthine/xanthine oxidase. AB - The xanthine/xanthine oxidase reaction produces reproducible amounts of oxygen derived free radicals that oxidize human oxyhemoglobin (Hb). We monitored the kinetics of the oxidation of stripped Hb (sHb), purified HbA0 and alpha-alpha cross-linked Hb (HbXL99 alpha) at [Hb] in the 5 to 150 microM (heme) range. For increasing [Hb], the oxidation halftime (t1/2) increased for all Hbs, but t1/2 was always less for HbXL99 alpha than for HbA0 and sHb. Such feature was attributed to the lower affinity for O2 of HbXL99 alpha and may represent a serious problem for use of this Hb as blood substitute. PMID- 7994375 TI - Hemoglobinuria in rats: a sensitive test of renal filtering and absorption of PEG hemoglobin, a red blood cell substitute. AB - Hemoglobinuria, defined as hemoglobin or hemoglobin subunits in the urine, is an easily monitored, sensitive indicator of renal handling of hemoglobin-based blood substitutes. Hemoglobin tetramer dissociation increases filtration by the kidneys. When the rate of filtration exceeds reabsorption, hemoglobinuria occurs. This study investigates the renal filtration and absorption of polyethylene glycol-modified bovine hemoglobin by monitoring for hemoglobinuria in several model systems. PMID- 7994376 TI - Vasoconstrictor effects in isolated rabbit heart perfused with bis(3,5 dibromosalicyl)fumarate cross-linked hemoglobin (alpha alpha Hb). AB - To study the mechanism by which cell-free hemoglobin preparations may alter coronary vascular reactivity, we investigated the effect of human hemoglobin cross-linked between alpha chains with bis(3,5-dibromosalicyl)fumarate (alpha alpha Hb) on the vasomotor response to acetylcholine (ACh) in isolated perfused rabbit hearts. Dose-response curves were generated by monitoring the increase in coronary pressure during serial addition of 0.2-10 microM ACh before, during and after 20 min infusion of three test solutions: a) 0.1 g/dl alpha alpha Hb (62 microM heme); b) 0.1 g/dl alpha alpha Hb plus 60 microM deferoxamine (DFO); c) 50 microM NG-nitro-L-arginine methyl ester (L-NAME), a specific inhibitor of nitric oxide (NO) synthase. We found that the sensitivity to ACh-induced vasoconstriction was significantly potentiated in the presence of alpha alpha Hb and L-NAME. In addition, this response was only partially reversed after removal of alpha alpha Hb, except when DFO was simultaneously infused with the alpha alpha Hb solution. These findings are consistent with the idea that both NO binding to hemoglobin and iron-mediated oxygen free radical generation contribute to an altered coronary vasomotor responsiveness induced by cell-free hemoglobin. PMID- 7994377 TI - Prevention of side effects by hemoglobin solutions; the selection of optimal test models, especially concerning thrombogenicity. AB - Modification of hemoglobin (Hb) by crosslinking and polymerization results in an improved oxygen release capacity and a prolonged vascular retention time. Modification improves the efficacy and prevents certain side effects. It eliminates leakage of Hb through the kidneys and accumulation in the tubuli. Another important issue is the degree of purification of Hb solutions. Traces of membrane fragments may cause immunogenic and thrombogenic side effects. To determine the contamination with erythrocyte membrane fragments, we developed assays for glycophorin-alpha and phospholipids. Special models were evaluated for testing the maximum allowable level of membrane contamination. As an in vitro model for thrombogenicity we used confluent monolayers of human umbilical vein endothelial cells. These cells were incubated with Hb solutions and subsequently tested on tissue factor (TF) procoagulant activity. TF was tested by the factor VII-catalyzed activation of factor X. The lower detection limit of this assay for endotoxin was 0.5 ng/ml. Hb did not cause any tissue factor expression even after prolonged incubation. No cooperation was found within endotoxin. As an in vivo test on thrombogenicity we developed a guinea pig model in which we can follow the generation of fibrinopeptide A (FPA). This is one of the most sensitive markers for thrombin activation in vivo. When slightly contaminated Hb solutions (phospholipid content 2 nmol/ml) were infused in the presence of factor Xa at a dose (9 micrograms/kg) which in itself did not induce FPA generation, we observed an increase in FPA levels in the plasma from 1.2 +/- 0.4 ng/ml to 5.2 +/- 0.7 ng/ml. Factor Xa is used to mimic a stressed clinical condition with activated coagulation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7994378 TI - Diaspirin crosslinked hemoglobin: evaluation of effects on the microcirculation of striated muscle. AB - Hemoglobin-based oxygen carriers such as diaspirin-crosslinked hemoglobin (DCLHb) have been proposed for blood substitution due to their plasma expansion and oxygen transport capacity. This study investigates the effects of DCLHb on the microcirculation of striated muscle after moderate topload infusion and isovolemic exchange transfusion in awake hamsters. The skinfold chamber model in hamsters and intravital fluorescence microscopy were used for analysis of vessel diameter, red blood cell velocity (RBCV), leukocyte sticking to the microvascular endothelium, and macromolecular leakage in striated skin muscle. In each animal, arteriolar and postcapillary vessel segments were chosen and sequentially recorded on videotape (baseline). Animals were subjected to either topload infusion (10% of blood volume) or isovolemic exchange transfusion (hct 30%) of DCLHb followed by measurements at 10, 30, and 60 min thereafter. In vivo visualization of plasma and leukocytes was performed using FITC-dextran 150,000 and rhodamine 6G, respectively. No significant changes of vessel diameter and RBCV were observed after topload infusion or isovolemic exchange transfusion with DCLHb, either in postcapillary venules or in arterioles when compared with baseline values. Leukocyte sticking and macromolecular leakage were not found enhanced after administration of DCLHb. We conclude that the introduction of DCLHb-bound oxygen into the tissue does neither stimulate leukocyte adhesion nor impair endothelial integrity. PMID- 7994379 TI - Regional circulatory and systemic hemodynamic effects of diaspirin cross-linked hemoglobin in the rat. AB - Diaspirin cross-linked hemoglobin (DCLHb) (Baxter Healthcare Corporation) is a promising resuscitative fluid. The effect of DCLHb (400 mg/kg, i.v.), on regional circulation and systemic hemodynamics was studied in male Sprague-Dawley rats using a radioactive microsphere technique. Systemic hemodynamics, distribution of cardiac output, regional blood flow and vascular resistance were determined before (baseline) and 15, 30 and 60 min after the administration of DCLHb. Infusion of an equal volume of saline did not produce any significant change in systemic hemodynamics or regional circulation. DCLHb produced an increase (79%) in the mean blood pressure which lasted for more than 60 min. Heart rate, cardiac output and stroke volume were not significantly affected, while total peripheral resistance was increased after the administration of DCLHb. DCLHb produced significant increases in blood flow to the heart, gastrointestinal tract (GIT), portal system and skin. The blood flow to the kidney, brain and musculoskeletal system was not significantly affected by DCLHb. The vascular resistance was not altered in the heart, brain, GIT, portal system, kidney or skin, but there was a marked increase in the vascular resistance in the musculoskeletal system. There was a significant increase in the percentage of cardiac output to visceral organs like heart, GIT and portal system, while a marked decrease in the percent cardiac output to musculoskeletal system was observed with DCLHb. It is concluded that the blood flow to most of the organs is either increased or is not affected by DCLHb. PMID- 7994380 TI - Diaspirin cross-linked hemoglobin (DCLHB): involvement of adrenergic mechanisms in the pressor effect. AB - Diaspirin cross-linked Hemoglobin (DCLHb) (400 mg/kg, i.v.), a resuscitative solution, produces a pressor effect in rats and several other species. Studies were conducted to determine the role of the central nervous system and adrenal medulla in the pressor effect of DCLHb in rats. Intravenous administration of DCLHb produced an increase in blood pressure in cervical sectioned animals, which was comparable to that observed in normal rats. This indicates that the pressor effect of DCLHb was mediated through the peripheral vascular system rather than through the central nervous system. DCLHb produced a pressor effect in bilateral adrenal demedullated rats that was similar to normal rats, suggesting that the pressor effect is not through the release of catecholamines or other pressor substance from the adrenal medulla. The effects of DCLHb pretreatment on norepinephrine (0.5 microgram/kg), phenylephrine (5 micrograms/kg) and clonidine induced blood pressure and heart rate responses were also studied. DCLHb significantly potentiated the pressor response to norepinephrine and phenylephrine. Clonidine normally produces a fall in blood pressure by acting on the central alpha-adrenoceptors, and a rise in blood pressure by stimulating the peripheral vascular alpha-adrenoceptors. DCLHb produced a marked potentiation of the pressor response to clonidine (75 micrograms/kg, i.v.), that masked the central depressor effect. The specificity of the potentiation was confirmed by using phenoxybenzamine, prazosin, and yohimbine. In order to exclude the contribution of a centrally induced cardiovascular effect of clonidine, further studies were carried out in cervical sectioned rats. DCLHb markedly potentiated the pressor effect of clonidine (25 micrograms/kg, i.v.) in cervical sectioned rats. This potentiation could be attenuated by prazosin and yohimbine.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7994381 TI - Coagulation responses of human plasma after hemodilution with hemoglobin solution in-vitro. AB - To assess the potential for interference of Hb with the normal coagulation mechanism, we performed in-vitro hemodilution tests. Platelet rich plasma (PRP) was prepared from citrated blood samples of 5 normal volunteers diluted 3:1, 1:1, and 1:3 volume ratio with human stroma-free hemoglobin solution (SFH) or human albumin (HSA). Coagulation kinetics and clot strength were assessed with a thrombelastograph (TEG). Extrinsic and intrinsic coagulation factors were assessed measuring prothrombin time (PT) and activated partial thromboplastin time (aPTT) with an optical coagulation timer. Statistical significance was assessed using ANOVA and Neuman-Keuls tests at p < 0.05. At all dilutions, SFH diluted plasma showed significantly prolonged initial rate of clot formation compared to undiluted control or HSA (p < 0.05). However, there was no difference in formed clot strength between SFH and HSA. At high Hb concentrations Hb seems to interfere with the optical measurements of coagulation times (particularly aPTT). SFH appears to interfere with the initial phase coagulation mechanism in human plasma in-vitro; further study is needed to clarify the cause. In measuring coagulation times of plasma containing Hb a non-optical instrument should be considered. PMID- 7994382 TI - Iron-58 and neutron activation analysis: a non-radioactive method for tracing hemoglobin iron. AB - To develop a non-radioisotopic alternative to radioactive Fe-59 as a hemoglobin iron tracer, we evaluated Fe-58 and neutron activation analysis (NAA). Upon irradiation with thermal neutrons, stable isotope Fe-58 is converted to radioactive Fe-59 through (n,gamma) neutron reaction; its radioactivity measured by a gamma counter is proportional to the original Fe-58 present. Organ samples from rats infused with Hb or saline were analyzed along with a 10 mg Hb as a standard (105 nanograms of Fe-58). The measured values of Fe-58 in tissues were compared with those derived from the literature tissue iron contents. The amount of Fe-58 in normal tissue is extremely low yet detectable by NAA demonstrating high sensitivity. Measured values of Fe-58 from tissues were generally correlated well with literature derived values (e.g., brain: 0.19 and 0.15 ng/mg tissue; kidney: 0.6 and 0.7 ng/mg tissue, respectively). The results indicate that Fe-58 can be used as a non-radioactive tracer for absorption, distribution, metabolism, and distribution studies of hemoglobin-based oxygen carriers. PMID- 7994383 TI - Denatured hemoglobin increases human blood mononuclear cell procoagulant effect. AB - PURPOSE: To study the effects of the common contaminants of hemoglobin solutions, red cell stroma, bacterial endotoxin, and denatured hemoglobin on the causes of the thrombotic lesions which have been reported in animal experiments after hemoglobin administration. PROTOCOL: Human blood mononuclear cells were isolated on Ficoll-Hypaque gradients and incubated with hemoglobin from the LAIR production facility, red cell stroma, bacterial endotoxin (E. coli, Wittaker Bioproducts), and hemoglobin denatured by boiling. Incubations were performed separately and in combinations. Mononuclear cells were then lysed and assayed for procoagulant activity in a recalcification time assay. RESULTS: Only bacterial endotoxin and hemoglobin denatured by boiling increased the procoagulant activity of human blood mononuclear cells. Denatured hemoglobin mixed one part in eight with undenatured hemoglobin increased mononuclear cell procoagulant activity by more than ten-fold that of the undenatured hemoglobin control. CONCLUSIONS: The study suggests that denatured but not undenatured hemoglobin causes increased blood procoagulant activity which is thought to be a marker of macrophage activation. These findings suggest a possible mechanism of toxicity of cell-free hemoglobins and the need for sensitive measures of hemoglobin denaturation. PMID- 7994384 TI - Mixtures of erythrocytes and acellular fluids: an in vitro evaluation. AB - To evaluate the biophysical properties of two acellular resuscitative fluids, experiments were performed using mixtures of these with suspensions of red blood cells. Two acellular resuscitative fluids were synthesized using a diacid to tetramerically stabilized hemoglobin and then complexing it with either a hydroxyethyl starch or a Tetronic Polyol. The new polymers were characterized with respect to the molecular weight, second virial coefficient and intrinsic viscosity. These fluids were then combined with red cells and the following measurements were made: non-Newtonian flow properties, malonamide induced hemolytic kinetics, sedimentation rates and oxygen transport. The in vitro evaluation indicates that these compounds are effective hemodiluents, offer protection to the red cell membrane and do not cause erythrocyte aggregation. The oxygen transport was satisfactory. PMID- 7994385 TI - Application of aqueous two-phase systems in separation/purification of stroma free hemoglobin from animal blood. AB - Aqueous two-phase system (ATPS) is suitable for treatment of biological materials. It has been traditionally employed in the separation of product from fermentation broth, and in the extraction of large-molecule proteins from colloid solution. The separation method based on ATPS features simple, rapid and continuous operation with low equipment cost. A PEG/Salt aqueous two-phase system is studied, and developed for hemoglobin (Hb) separation from animal bloods. Stroma free hemoglobin (SFHb) was extracted from 200ml packed red blood cells by the two-stage aqueous two-phase system and subsequently was desalted and dialyzed by ultrafiltration. It took only 2.5hr to complete overall process to purify SFHb. The purity of SFHb was analyzed by HPLC and IEF (silver staining). Large partition coefficients of Hb have been observed with proper selection of PEG molecular weight, added concentrations of PEG and salt in each phase. The SFHb of very high purity which is free of other proteins (< 0.1% impurity) and phospholipids (< 2% impurities) may be obtained from human packed RBCs. A two stage extraction design using ATPS separation concept is very simple and useful for purification of SFHb. The method may be further developed to offer potent technology for hemoglobin separation from animal blood and future production industry of blood substitutes. PMID- 7994386 TI - Convenient method to purify hemoglobin. AB - A convenient method to purify Hb solution from outdated RBC has been established for the starting material of Hb-based blood substitutes. To prevent MetHb formation during the procedure, Hb in RBC was carbonylated in advance. Then RBC was mixed with organic solvent for hemolysis and centrifuged for removal of stroma. The resulting SFHb solution was heated at 60 degrees C and generated precipitates were removed out by centrifugation. The purity of Hb (25 g/dl) was confirmed by SDS-PAGE. IEF and oxygen binding property of the Hb solution also guaranteed its purity and no denaturation of Hb. This method is applicable to large scale production of the purified Hb for the starting material of Hb-based blood substitutes. PMID- 7994387 TI - Production of PEG-modified bovine hemoglobin: economics and feasibility. AB - Bovine hemoglobin has many advantages as a blood substitute: a) it's ready availability; b) it's low cost; c) it's oxygen carrying capacity; and d) the ease with which it can be modified with polyethylene glycol (PEG) to improve its pharmacokinetic profile. This study investigates the potential of PEG-modified bovine hemoglobin as a cost-effective blood substitute. PMID- 7994388 TI - Structural and oxygen-binding properties of divinyl-sulfone-reacted bovine hemoglobin as a function of protein ligation state and reactant concentration. AB - Bovine hemoglobin (HbBv) was reacted with divinyl sulfone (DVS) at 2-4 degrees C and pH 7.4 for 24 h. Two procedures were employed: (1) low concentration (conc.) of oxygenated HbBv (ligand O2) and low molar ratio of DVS/oxyHbBv (25 ml of 8% oxyHbBv, 0.01 M DVS); (2) low conc. of deoxygenated HbBv (no ligand) and low DVS/deoxyHbBv molar ratio (25 ml of 8% deoxyHbBv, 0.01 M DVS). The nonpolymerized purified products of procedures 1 and 2 were designated oxyHbBv-DVS and HbBv-DVS. Utilizing a high conc. solution of oxyHbBv-DVS and a relatively high molar ratio of DVS/oxyHbBv-DVS (25 ml of 15% oxyHbBv-DVS, 0.03 M DVS) it was possible to aerobically polymerize the modified hemoglobin (procedure 3). Similarly it was possible to anaerobically polymerize HbBv-DVS (25 ml of 15% HbBv-DVS, 0.03 M DVS)(procedure 4). The polymerized products of procedures 3 and 4 were designated oxyPoly HbBv-DVS and Poly HbBv-DVS. The four isolated products were characterized structurally using SDS-PAGE and gel-permeation HPLC and functionally employing a Hemox-analyzer at 37 degrees C, pH 7.4 and 0.15 M Cl. Both oxyPoly HbBv-DVS (P50 = 13 mm Hg, n = 1.1) and Poly HbBv-DVS (P50 = 61 mm Hg, n = 1.6) were shown to be mixtures of intermolecularly-crosslinked hemoglobin. OxyHbBv-DVS (P50 = 13 mm Hg, n = 1.3) was shown to be an intramolecularly-crosslinked 64 kDa material, whereas HbBv-DVS (P50 = 52 mm Hg, n = 1.9) was found to be an intramolecularly-modified 64 kDa derivative, but not an intramolecularly-crosslinked one.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7994389 TI - Human hemoglobin anaerobically reacted with divinyl sulfone: a source for oxygen carriers. AB - Human hemoglobin (HbA) was reacted in anaerobic conditions with divinyl sulfone (DVS). The structural and oxygenation properties of the resulting chemically modified product were studied in order to assess its potential as a physiological oxygen carrier. The reaction was carried out anaerobically at 25 degrees C and pH 7.4 for 3 h. Quenching was performed with lysine-HCl solution and the resulting solution dialysed to remove unbound DVS and excess lysine. The product, designated Poly HbA-DVS, was characterized structurally using gel-permeation HPLC and SDS-PAGE and functionally employing a Hemox-analyzer at 37 degrees C and pH 7.4. From gel-permeation HPLC it was estimated that about 60% of the starting material was polymerized, with a molecular mass range from 130 to about 500 kDa, and about 40% remained monomeric with a molecular mass of 64 kDa. The virtual absence of a 32 kDa band from the SDS-PAGE pattern of the last eluting HPLC peak and the oxygenation properties of this peak material (P50 = 33 mm Hg, n = 2.2; P50 very different from the approximately 1.5 mm Hg associated with native HbA solution) indicated that the monomeric (64 kDa) component was modified, but virtually noncrosslinked, within the tetramer. The product solution, Poly HbA DVS, had a P50 of 35 mm Hg, a Hill coefficient n of 1.8 and a methemoglobin content of 5-7%. This material has characteristics appropriate for an oxygen carrier, and can probably be used as such in perfusional and transfusional fluids. PMID- 7994390 TI - Recombinant hemoglobin A produced in transgenic swine: structural equivalence with human hemoglobin A. AB - Recombinant human hemoglobin A produced by coexpressing human alpha and beta globin genes in swine, and purified from the lysate of transgenic swine has been subjected to detailed protein chemical analysis. These structural studies involving laser desorption mass spectrometry, separation of globin chains by RPHPLC, amino terminal sequence analysis of the isolated globin chains, the tryptic peptide mapping of the purified globin chains and the amino acid composition analysis of the purified tryptic peptides of globin chains have established the primary structural equivalence of the globin chains of the transgenic swine derived hemoglobin A with that of human hemoglobin A. These results demonstrate that the transgenic swine system correctly translates the human alpha and beta globin m-RNA; carries out the correct cotranslational processing of globin chains, and does not introduce any unwanted post translational modifications into the mature chains. Thus, the transgenic swine expression system is an excellent approach for the production of HbA for developing an effective hemoglobin based oxygen carrier. PMID- 7994391 TI - Diaspirin crosslinked hemoglobin (DCLHb): characterization of the process and the product manufactured under GMP requirements for clinical studies. AB - Initiation of Clinical Trials in 1992 necessitated product manufacture under FDA Good Manufacturing Practice (GMP) requirements. To this end, all product components used were characterized to meet established requirements and processes and analytical methods were validated to confirm and document their utility and reproductibility. Manufacture of multiple 50+ liter lots of 10%g DCLHb under GMP requirements resulted in a pure and homogeneous product which reproducibly met a rigorous and complete set of product specifications. Final release testing of five consecutive GMP lots showed hemoglobin concentrations of 10.2 +/- 0.2g%, pH of 7.33 +/- 0.02 (37 degrees C), methemoglobin concentrations of 3.2 +/- 0.6%, degree of crosslinking of 99.8 +/- 0.1% and a P50 of 32.4 +/- 1.0 mmHg (37 degrees C). The mean overall yield for production of these five lots was 55 +/- 2%. Products were all endotoxin free as indicated by rabbit, cytokine and LAL testing (< 0.06 EU/mL); a critical characteristic for a molecule which may bind endotoxin. All lots were sterile as indicated by compendial testing. PMID- 7994392 TI - Enzymatic protection from autoxidation for crosslinked hemoglobins. AB - The autoxidation rates of hemoglobins crosslinked between the alpha subunits (alpha 99XLHb A) and between the beta subunits (beta 82XLHb A) were reduced in the presence of catalase and/or superoxide dismutase. In the presence of catalase the rate for alpha 99XLHb A decreased 2.3 fold and for beta 82XLHb A, 1.9 fold. Superoxide dismutase reduced the rate 1.6 fold for alpha 99XLHb A and 1.8 fold for beta 82XLHb A. In the presence of both catalase and superoxide dismutase the rate of autoxidation decreased by 3.0 fold in alpha 99XLHb A and 4.0 fold in beta 82XLHb A. The presence of catalase and superoxide dismutase or both in the crosslinked hemoglobin samples increases the autoxidation half-life of oxyhemoglobins. This suggests that crosslinked hemoglobins to be used as blood substitutes could be protected from oxidation in storage by these enzymes. PMID- 7994393 TI - Thermal stabilities of hemoglobins crosslinked with different length reagents. AB - Bis(3,5-dibromosalicyl) succinate and glutarate were used to crosslink met-, oxy- and deoxyhemoglobins. The added flexibility of these reagents compared to the fumarate analog resulted in a more heterogeneous product but did not greatly affect the maximum thermal stability of the crosslinked hemoglobins. PMID- 7994394 TI - Influence of the polymerization step alone on oxygen affinity and cooperativity during production of hyperpolymers from native hemoglobins with crosslinkers. AB - The aim of this study was to find out how the polymerization per se changes oxygen affinity (P50) and cooperativity (n50) of various soluble huge hyperpolymers prepared from native hemoglobins by crosslinking. Increase of cooperativity would be expected considering natural hemoglobin networks. Those hyperpolymers with molecular weights of some 10(6) g/mol are candidates for artificial oxygen-carrying blood additives rather than volume substitutes. Human and bovine hemoglobin reacted with several crosslinkers (2,5 diisothiocyanatobenzenesulfonate (DIBS); 4,4'-diisothiocyanatostilbene-2, 2' disulfonate (DIDS); 1,3-butadiene diepoxide (BUDE); glutaraldehyde (GDA)) in concentrated (case 1) and diluted (case 2) hemoglobin solutions. With high concentration hyperpolymer and with low concentration only monomer products were obtained. P50 and n50 of the products were determined at pH = 7.4, PCO2 = 40 mmHg, temp. = 37 degrees C. The difference of properties in both cases are regarded as the influence of polymerization per se. Considering this difference we found with almost all combinations of hemoglobin and crosslinker an increase of O2 affinity, with DIBS and DIDS cooperativity was not changed and with BUDE and GDA it was decreased. As compared with native hemoglobin loss of cooperativity is considerable in any combination and condition, but comparing human and bovine hemoglobin the first seems to maintain better cooperativity. In contrast bovine hemoglobin as compared with human hemoglobin maintains better or even decreases its O2 affinity upon reaction with the crosslinkers forming both, monomer and hyperpolymer products, especially in the deoxy state. DIBS and DIDS react very similarly.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7994395 TI - Chimeric hemoglobin subunits: functional properties of a recombinant beta/alpha hemoglobin. AB - Our goal was to design a single hemoglobin subunit able to assemble into a stable tetrameric structure with cooperative O2 binding and low oxygen affinity. We have synthesized in E. coli a chimeric beta/alpha globin subunit composed of the first 73 residues of the beta chain and the last 73 residues of the alpha chain. Molecular building indicated that this construction could result in Hb homotetramers possessing the alpha 1 beta 2 interface, responsible for the heme heme interaction in Hb heterotetramers. The results show that the chimeric subunits assemble into tetramers which bind oxygen reversibly without cooperativity but with an oxygen affinity slightly lower than observed for human Hb. The strong effector RSR 4 lowers the oxygen affinity. Kinetics of CO recombination in the presence of RSR 4 reveal a biphasic bimolecular rebinding. Functional studies suggest that the quaternary structure of the oligomer is intermediary between R-and T-state. PMID- 7994396 TI - Functional properties of beta(NA1)Val-deleted,(NA2)His-->Met hemoglobin synthesized in Escherichia coli. AB - Bovine Hb (hemoglobin) has a low oxygen affinity in the absence of chloride ions and DPG. Because of the increasing interest of this Hb as a potential blood substitute we have engineered a human Hb mutant with the aim of mimicking the functional properties of bovine Hb. This was achieved by deleting residue beta NA1 Val and substituting a methionine for histidine at the beta NA2 position as previously suggested by Perutz and Imai in 1980. Our results show that the artificial mutant exhibits some of the characteristics of bovine Hb but does not show the low oxygen affinity which is measured in bovine blood. PMID- 7994397 TI - Bissulfosuccinimidyl esters of aliphatic dicarboxylic acids: a new class of 'affinity directed' beta beta crosslinkers of HbA. AB - The potential of sulfosuccinimidyl ester of suberic acid as an intramolecular crosslinker of HbA, directed to the positive charge rich domain of the protein (DPG pocket) has been investigated. The suberate ester introduced crosslinks between the beta-chains and inhibited the dissociation of HbA into alpha beta dimers. The facile crosslinking reaction seen with this suberate ester as compared to the absence of crosslinking with the diaspirin derivative of suberic acid suggests the strong 'steering' influence of the sulfosuccinimidyl moiety of the reagent to the targeted site. The application of this crosslinking approach in the preparation of Hb based blood substitutes is discussed. PMID- 7994398 TI - A convenient method for the determination of the solubility of hemoglobin and modified hemoglobins. AB - The removal of a single charged group can drastically alter the solubility of hemoglobin. Alterations in hemoglobin structure to make it of potential use as a blood substitute must produce derivatives which are sufficiently soluble to allow adequate oxygen delivery. We have developed a convenient method for examining modified hemoglobins. How the polymerization of Hemoglobin S is perturbed in the presence of modified hemoglobins is determined. To measure Hemoglobin S polymerization, a rapid temperature jump from 0 degree and a nitrogen atmosphere [1] are not required. In pH 7.4 phosphate buffers at concentrations greater than 2M containing sodium dithionite, dilute solutions (less than 1 mg/ml) of hemoglobin S aggregate at 30 degrees, or higher, after a delay time (minutes) which depends on the hemoglobin concentration. Light scattering can be used to quantify the extent of polymerization. Chemical modifications of Hemoglobin A can result in altered perturbation of Hemoglobin S polymerization as determined by this method. Modification of hemoglobin to provide suitable oxygen binding characteristics and crosslinking of subunits is a required preliminary to use of hemoglobin as an acellular blood substitute. These modifications often involve the elimination of charged groups from hemoglobin. Information on whether such modifications may have undesirable consequences with respect to solubility properties can be examined using the method described. PMID- 7994399 TI - Concepts of "tissue PO2" in relation to O2 delivery. AB - Resistance to O2 diffusion is reflected in the difference in pO2 between O2 reservoirs of hemoglobin (Hb) and myoglobin. The very low normal myocyte pO2 (less than one torr but adequate for optimal oxidative ATP synthesis) compared to venous pO2 indicates that blood does not achieve equilibrium with tissue during its passage through capillaries. In the lung, diffusion rate of O2 from alveolus to capillary is normally sufficient to achieve essential equilibrium. However, system-wide capillary pathology and reduced Hb saturation has been observed with distal local ischemia. In peripheral vascular disease (PVD) patients, we found a mean arterial pO2 of 77 torr (normal over 90 torr). Classical concepts based on "tissue pO2" values derived from venous blood or oxygen electrodes inserted into tissue need re-evaluation. Readings of O2 electrodes moved through tissue range widely from intracapillary levels down toward intracellular levels and do not reflect the pO2 of any particular site. Intravenous pO2 is the result of residual O2 after incomplete diffusion out of capillaries during transit through a tissue, and is not an equilibrium value with some tissue pool. The effect of HbO2 p50 on oxygen release during the passage of blood through a capillary bed, generally judged on the basis of percentage percent saturation at "tissue pO2", should be judged on the basis of the change in pO2 (the diffusion driving force) associated with a particular degree of HbO2 saturation at a particular p50. The thesis that O2 diffusion rate is a major determinant of oxygen delivery is supported by pO2 responses to treatment of PVD that does not alter blood flow or p50. PMID- 7994400 TI - Reaction of human endothelial cells to bovine hemoglobin solutions and tumor necrosis factor. AB - Human umbilical vein endothelial cells (HUVEC) were incubated for 24 hours with 0.1 mM or 0.3 mM of: [A] unmodified (U) Hb-FeIIO2; [B] UHb-FeIII; [C] UHb-FeIV OH; [D] polymerized low molecular weight Hb (< 400 kDa); [E] polymerized high molecular weight Hb (< 1,020 kDa); [F] polymerized low molecular weight Hb + Endotoxin (2.5 EU/mL); [G] rTNF alpha 100 pg/mL; [H] rTNF alpha 400 pg/mL; [I] rTNF alpha 800 pg/mL. The medium of the incubation was tested for LDH (index of cell injury), and for cytokines GM-CSF and IL-1 alpha released by the cells. The data suggests that oxidation status of the iron in the Hb molecule and concentration of Hb play an important role in causing EC injury. The highest toxicity was observed when EC were incubated with 0.1 mM of UHb-FeIV-OH (ferryl Hb) and no toxicity with 0.3 mM of Hb-FeIII (ferric-Hb). The direct stimulation of EC by Hb for the production of IL-1 was limited, related only to high molecular weight Hb polymers or to Hb+E, however GM-CSF expression was increased by almost all Hb forms. TNF induced dose-related injury (R2 = 0.986), and dose related release of IL-1 (R2 = 0.977). A different EC reaction was observed on the release of GM-CSF. Intermediate levels of TNF (400 pg/mL) increased the expression of this cytokine, while high levels (800 pg/mL) blocked its release. PMID- 7994401 TI - Significant prolongation of guinea pig heart contraction transplanted in rat after removal of anti-xeno-antibodies by whole body rinse-out (WBRO) with hemoglobin solution. AB - PURPOSE: In order to investigate effectiveness of removal of the anti-xeno- antibodies in xenotransplantation (xeno Tx), WBRO using pyridoxalated-human hemoglobin-polyethyleneglycol conjugate (PHP solution) was performed prior to transplantation (Tx) of a guinea pig heart in a rat. MATERIALS & METHOD: Experiment I. Removal of the immunoglobulins and the anti-guinea pig lymphocytotoxic antibody (ALA) by WBRO. Exchange transfusion with the PHP solution was done in the Tx-expected rats until a hematocrit lowered below 5% (n = 11). Experiment II. Xeno heart Txs. Guinea pig hearts were transplanted into rats without immunosuppressants 1) without (n = 8) or 2) with the WBRO (n = 8). RESULTS: Experiment I. Levels lowered to 14% in IgG, 17% in IgA and 6% in IgM, respectively, to initial values after the WBRO. An ALA titer lowered from 4 X (+) to 1 X (-) after the WBRO. Experiment II. An average heart contraction period was 10.4 +/- 1.8 minutes 1) without the WBRO in contrast to 472.5 +/- 4.8 minutes with the WBRO (p < 0.01). CONCLUSION: WBRO using PHP solution is effective in removal of the anti-xeno-antibodies and consequent prolongation of survival of the xenograft. PMID- 7994402 TI - PEG-hemoglobin: an efficient oxygen-delivery system in the rat exchange transfusion and hypovolemic shock models. AB - Polyethylene glycol-hemoglobin (PEG-Hb is a purified bovine hemoglobin molecule modified by polyethylene glycol. Oxygen delivery to the tissue, in rat exchange transfusion and hypovolemic shock models, was studied to determine whether the oxygen-carrying capacity of PEG-Hb is as efficient as red blood cells. PMID- 7994403 TI - Normal oxygen tension restored in the ischemic rat liver model by PEG-hemoglobin. AB - Cell damage initiated during ischemia, as a result of oxygen depletion, continues during reperfusion, and recovery is dependent on the length of the ischemic period. This study investigates the effect of polyethylene glycol-modified hemoglobin (PEG-Hb) on recovery of tissue oxygen tension after induced ischemia. PMID- 7994404 TI - Diaspirin crosslinked hemoglobin (DCLHb): effect of hemodilution during focal cerebral ischemia in rats. AB - The efficacy of hemodilution therapy, to ameliorate cerebral ischemia, is limited by an accompanying decrease in oxygen content. We assessed the effect of hemodilution, with diaspirin cross-linked hemoglobin (DCLHb), on cerebral blood flow (CBF) and infarct after middle cerebral artery occlusion (MCAo). Rats (n = 36) were alloted to a control group in which hematocrit (Hct) was not manipulated, or reduced with DCLHb to 30% (30/DCLHb), 16% (16/DCLHb), or 9% (9/DCLHb). After MCAo, the brain area with a CBF of 0-10 ml.100g-1.min-1 was determined. This area was decreased in the 30/DCLHb and 16/DCLHb groups vs the Control group; and was less in the 9/DCLHb group vs the other groups. Different rats (n = 49) were hemodiluted with DCLHb or Albumin (Alb): Control, 30/Alb, 30/DCLHb, 16/DCLHb, or 9/DCLHb. After 3-hr of MCAo and 2-hr of reperfusion, infarct area was determined. Brain infarct was less in the 30/DCLHb and 16/DCLHb groups vs the Control and 30/Alb groups; and was less in the 9/DCLHb group vs the other groups. The results of this study support the hypothesis that hemodilution with DCLHb decreases cerebral ischemia in a dose-dependent manner, and in terms of brain ischemia is a more proficient hemodiluting fluid than albumin. PMID- 7994405 TI - Diaspirin crosslinked hemoglobin (DCLHb): control of pressor effect with anti hypertensive agents. AB - Diaspirin crosslinked hemoglobin (DCLHb) administration elevates mean arterial pressure (MAP). The purpose of this study was to determine whether commonly used antihypertensive agents could control this pressor effect in rats. Awake rats were injected intravenously (i.v.) with 280 mg/kg of DCLHb. Fifteen minutes later when MAP was 25-30% above baseline and heart rate (HR) was reciprocally decreased, prazosin (2 mg/kg;an alpha adrenergic blocker), nitroglycerine (NTG; 10-150 mcg/min; a nitrovasodilator), nicardipine (0.204-0.08 mg/hr; a calcium channel blocker) or labetalol (5 mg/kg; an alpha/beta adrenergic blocker) was administered i.v. All four classes of antihypertensive agents promptly restored MAP to baseline. Coincident with the return of MAP to baseline, HR was restored to baseline in prazosin and NTG treated animals, however, bradycardia persisted in those animals treated with nicardipine and labetalol, most likely due to the negative chronotropic properties of these agents. We conclude that the pressor effect of DCLHb can be readily controlled with at least four different classes of commonly used antihypertensive agents. PMID- 7994406 TI - Oxygenation of the rat 9L gliosarcoma and the rat 13672 mammary carcinoma with various doses of a hemoglobin solution. AB - Tumor oxygen tensions were measured using a computer controlled pO2 microelectrode in two preclinical solid tumor models, the rat 9L gliosarcoma and the rat 13672 mammary carcinoma. Tumor oxygenation profiles were determined under four conditions: 1) normal air breathing, 2) carbogen (95% O2/5% CO2) breathing, 3) after intravenous administration of a solution of ultrapurified polymerized bovine hemoglobin with normal air breathing and 4) after intravenous administration of a solution of ultrapurified polymerized bovine hemoglobin with carbogen breathing. Both tumors had severely hypoxic regions under normal air breathing conditions. Although carbogen breathing increased the oxygenation of the better oxygenated portions of the tumor, it did not impact on the severely hypoxic tumor regions. Administration of the hemoglobin solution was effective in increasing the oxygenation throughout both tumors under normal air breathing conditions. The addition of carbogen breathing to administration of the hemoglobin solution eliminated severe hypoxia in the 9L gliosarcoma and markedly reduced the severely hypoxic regions of the 13672 mammary carcinoma. PMID- 7994407 TI - Measurement of interleukin-6 production by monocytes for in vitro safety testing of hemoglobin solutions. AB - Induction of interleukin-6 (IL-6) production by isolated human mononuclear blood cells was taken as in vitro model for the induction of inflammatory reactions. The model was very sensitive to bacterial endotoxin (detection limit < 10pg/ml). Hemoglobin (Hb) solutions, prepared under non-sterile conditions also induced IL 6 production, which correlated with a positive reaction in the Limulus assay. Purification of the Hb solutions with a detergent prevented IL-6 production, showing that pure Hb itself does not activate the monocytes. We conclude that this assay is a useful and sensitive test of contamination with components that can induce inflammatory reactions, especially microbial products. PMID- 7994408 TI - Encapsulation of hemoglobin in non-phospholipid vesicles. AB - The efficiency of encapsulating hemoglobin in non-phospholipid liposomes by rapidly mixing hemoglobin with lipids heated above their solid-liquid phase transition temperature was examined. Human hemoglobin was mixed at 55-60 degrees C with a lipid solution containing polyoxyethylene-2 cetyl ether and cholesterol (molar ratio, 3:1) at 60-65 degrees C. Repeated mixing was carried out through a high-shear orifice, followed by rapid cooling and additional mixing. Lipid vesicles were heterogeneous in size, with diameters from approximately 300 nm to 10 microns. The non-encapsulated aqueous phase was removed by centrifugation, and total hemoglobin was determined spectrophotometrically. Encapsulation efficiency was calculated as the percentage of hemoglobin associated with the liposome phase (i.e., encapsulated) as a function of hemoglobin concentration and the aqueous:lipid hydration ratio. Hemoglobin concentrations were varied from 1 to 10 nM (in heme). Aqueous:lipid ratios of 8:1 and 4:1 were tested. Percent encapsulation varied from 13-30%, with the greatest efficiency, i.e., 30%, at a 4:1 hydration ratio of hemoglobin:lipid at 5.6 mM hemoglobin. PMID- 7994409 TI - Structure and solution properties of lipidheme-microsphere. AB - Triglyceride microsphere emulsified with phospholipid derivative of heme (5,10,15,20-tetrakis[alpha,alpha,alpha,alpha-o-[2,2-dimethyl-20- [2 (trimethylammonioethoxy) phosphonatoxy]eicosanamido]phenyl]porphinatoiron(II); lipidheme) provides a totally synthetic artificial red cell (lipidheme microsphere; LH-M). Its structure, solution properties and O2 binding ability are described. The particle diameter of the LH-M was ca. 90 nmo elucidated by electron microscopy. Viscosity of the LH-M suspension (approximately 1.5 cP) was much lower than that of human blood and the viscosity of mixed system of LH M/human blood (1/1(v/v)) was 2.5 cP. Specific gravity, osmotic pressure, and colloid osmotic pressure of the LH-M suspension also satisfied the physiological needs. The LH-M can bind O2 reversibly in response to O2 pressure (P50(O2): 41 torr (pH 7.4, 37 degrees C)). O2 solubility of the LH-M was more than that of human blood caused by its high heme concentration. PMID- 7994410 TI - Characteristics of Hb-vesicles and encapsulation procedure. AB - The performance of Hb-vesicles depends on the weight ratio of Hb to lipid ([Hb]/[Lipid]). This value is improved by lowering the number of bilayer membrane of the vesicle and raising the concentration of Hb in the interior of the vesicle. Maximum [Hb]/[Lipid] ratio was obtained at ca. pH 7, that would relate to the isoelectric point (pI) of Hb at 25 degrees C. On the other hand, the [Hb]/[Lipid] ratio decreased with ionic strength and increased with lowering temperature. The Hb-vesicles encapsulating 40 g/dl Hb with only one bilayer membrane were isolated by using the difference in the density of the vesicles. PMID- 7994411 TI - Preparation and characterisation of poly(lactic acid) hemoglobin microspheres. AB - For many years, a lot of research effort has been carried out with a view to preparing blood substitutes. Our group has developed a process of encapsulation of hemoglobin in polylactid microspheres. An aqueous solution of hemoglobin was emulsified into a solution of polymer in methylene chloride to form a W/O emulsion. This primary emulsion was then added to a external aqueous phase under stirring until the evaporation of methylene chloride. The microspheres were separated by filtration and washed with distilled water. Microspheres were spherical and their sizes vary between 10 and 500 microns. More than 80% of the hemoglobin was encapsulated. From the absorption spectra of hemoglobin from microspheres, we did not notice any alteration of the oxygen carrier. The dissociation curve of the hemoglobin demonstrated the permeability of the polymeric wall of these microspheres to oxygen. This curve was relatively sigmoidal and presented a P50 similar to that of free hemoglobin in the same experimental conditions. A cellulose's acetate gel electrophoresis of hemoglobin extracted from the microspheres showed one band that correlates with intact hemoglobin. These results suggest that hemoglobin does not interact chemically with the polymer matrix and that the process of microencapsulation does not alter the hemoglobin molecule. PMID- 7994412 TI - Characteristics of neo red cells, their function and safety: in vivo studies. AB - A new type of artificial oxygen carriers, the Neo Red Cells (NRCs) have been developed and investigated for oxygen transporting efficiency and safety in experimental animals. Stroma free hemoglobin from outdated human red blood cells together with inositol hexaphosphate as an allosteric effector under sterile, pyrogen free condition were encapsulated in liposomes and then were coated with polyethylene glycol bond to hydrogenated soy phosphatidylethanolamine as a surface modifier to prevent aggregation of NRCs in plasma. The efficiency of the NRCs in tissue oxygenation was studied in rabbits which were made severely anemic by drawing 85% of their blood and immediately replacing it with NRC solution. The animals, all recovered to pre-anemic conditions within 6-8 hr and lived normally until being sacrificed, 6 months after the exchange transfusion. The circulation half-life and tissue distribution of NRCs were studied using radiolabeled NRCs. Within the circulation, the half-life of NRCs was 21 hr and extravascularly, they were distributed mainly in and metabolized by the reticuloendothelial system within 7 days. Our observations suggest that the NRCs prepared and investigated in this study are efficient oxygen carriers without causing serious adverse reactions and can be prepared free from pathogenic micro-organisms by special filtration technique before encapsulation of Hb. Currently, experiments are ongoing to control auto-oxidation of oxyHb to metHb which is higher in NRCs than in native red cells at physiological conditions. PMID- 7994413 TI - Toxicity of liposomes containing low mol% of dienoyl phosphocholine to blood: use of carboxymethyl chitin to reduce toxicity. AB - Toxic effects of liposomes composed of the synthetic lipid, 1,2-bis(octadeca-2,4 dienoyl)-sn-glycero-3-phosphocholine (C18DENPC) and cholesterol (Cho) were studied. In the present work, we have explored, 1) fusion between C18DENPC/Cho liposomes and erythrocyte ghost (EG) membranes with resonance energy transfer assay, 2) hemolysis induced by C18DENPC/Cho-liposomes and 3) turbidity changes in native plasma on contact with C18DENPC/Cho-liposomes, in the presence or absence of carboxymethyl chitin (CM-chitin). In the absence of CM-chitin, extents of fusion, hemolysis and turbidity changes in native plasma increased with the decrease in C18DENPC content. In the presence of CM-chitin at a concentration of 10(-3) or 10(-2)% (w/v), fusion of C18DENPC/Cho-liposome with EG was inhibited. Extents of hemolysis and turbidity changes in native plasma induced by C18DENPC/Cho-liposomes were reduced depending upon CM chitin concentration. PMID- 7994415 TI - Two types of totally artificial red blood cell substitutes liposome embedded heme(L/H) and lipidheme/microsphere(LHM). AB - Two types of totally artificial oxygen carriers were produced (1)by embedding synthetic lipidhemes (as oxygen carriers) in bilayers of liposomes as vehicles of lipidhemes (L/H) and (2)by covering clinically available fat droplets (triglyceride microspheres) with synthetic lipidhemes (LHM). Fat droplets were used as vehicles of lipidhemes. Their oxygen carrying ability in vivo was examined in beagles undergoing hemorrhagic shock. L/H delivered 15.7 to 19.2% of total oxygen delivery. From 12.7 to 24.4% of total oxygen consumption was from L/H. LHM delivered 11.6 to 7.3% of total oxygen delivery. From 13.1 to 16.4% of total oxygen consumption was from LHM. These totally synthetic red blood cell substitutes can be candidates for future clinical testing. PMID- 7994414 TI - Submicron biodegradable polymer membrane hemoglobin nanocapsules as potential blood substitutes: a preliminary report. AB - We used biodegradable polymers like polylactic acid, poly-isobutylcyanoacrylate and others to prepare nanocapsules containing hemoglobin. We prepared the optimal mean diameters of between 0.08 to 0.12 micron (80-120 nm). They are spherical and homogeneous. The membrane thickness is 0.005-0.015 micron (5-15nm). With different formulation, the hemoglobin contents in the particles may be varied from 30-45%. Phospholipid is not required in bovine hemoglobin. It is required for human hemoglobin in order to retain cofactors required for optimal P50. The P50 of the biodegradable polymer membrane containing bovine hemoglobin was between 27-29 mmHg. This is the same P50 as bovine hemoglobin used in the preparation. Thus the procedure of preparation did not damage hemoglobin. PMID- 7994416 TI - Oxygen transport and in vivo parameters of artificial red cells (ARC). AB - Artificial red cells (ARC) are prepared by encapsulating Hb with a polymerizable phospholipid. Their physical stability is very high and long-term preservation is possible in the frozen state. We examined the effect of blood parameters on the hematological and biochemical findings in transfused rats. The oxygen transport capacity of ARC in vivo were also tested by exchange transfusion in beagles. The oxygen binding parameters were almost the same as those of red blood cells (i.e., P50, Hill's coefficient, and oxygen transport efficiency (OTE) were 30 mmHg, 2.5, and 30%, respectively). The blood parameters after transfusion showed no significant changes when compared with the control. The oxygen transport capacity was of the same efficiency as red blood cells. PMID- 7994417 TI - Circulation profile of technetium-99m labeled liposome encapsulated hemoglobin in a 10% or 50% rat hypovolemic shock model. AB - The circulation kinetics and organ biodistribution of liposome encapsulated hemoglobin (LEH) was determined non-invasively in hypovolemic rats using a technetium-99m (Tc-99m) liposome labeling procedure. Rats with an indwelling catheter had either 10% or 50% of their blood volume removed and replaced with an equal volume of LEH labeled with Tc-99m (Tc-99m LEH). Mean arterial pressures and heart rates were monitored throughout the experiment. Gamma camera images were acquired during the first 90 minutes following infusion of the Tc-99m LEH and at 20 hours post-infusion. Blood capillaries were drawn at various times to monitor Tc-99m activity and the amount of LEH remaining in circulation. There were significant differences in the kinetics and biodistribution for the two groups. In the 10% group, the LEH was removed quickly from circulation with only 0.9% remaining at 20 hours, while the 50% group had 51.2% at 20 hours. The liver and spleen were the major organs responsible for LEH clearance. The 20 hour biodistribution by tissue sampling showed that the 10% group had 37.6% in the liver and 34.3% in the spleen, while the 50% group had only 18.4% in the liver and 14.6% in the spleen. PMID- 7994418 TI - Diaspirin crosslinked hemoglobin (DCLHb): bioanalytical studies in swine. AB - These studies were a part of preclinical safety and efficacy studies of DCLHb. Their purpose was to analyze the characteristics of DCLHb during circulation, and the distribution of iron following the administration of DLCHb to swine. Swine were dosed (2 g/kg) with 10 g/dL DCLHb, infused intravenously at a rate of 1 mL/kg/min. Blood samples were collected up to 48 hours post-infusion for analysis. Tissue samples were obtained for iron determination. The data collected showed that the concentration of DCLHb in the plasma gradually decreased, while the concentration of methemoglobin remained low and essentially constant. The oxygen binding characteristics and stability of the crosslink were preserved following infusion, indicating that the DCLHb continued to function as an effective oxygen carrier. Iron concentrations in the liver and kidneys increased as expected, but plasma levels of iron did not saturate the iron binding capacity of transferrin, inferring a controlled process for the release of iron. PMID- 7994419 TI - Diaspirin crosslinked hemoglobin (DCLHb) polymerization. AB - By employing proprietary polymerization agents possessing specific binding groups and by completing diaspirin crosslinked hemoglobin (DCLHb) polymerization under specific conditions, we have selectively achieved the following objectives: (1) the P50 was adjusted to the physiologic range or left- or right-shifted; (2) the surface of DCLHb was modified ("decorated"); (3) DCLHb was polymerized but not decorated; (4) DCLHb was polymerized and decorated; or (5) DCLHb was site specifically modified and polymerized. PMID- 7994420 TI - Lipidheme-microsphere (LH-M). A new type of totally synthetic oxygen carrier and its oxygen carrying ability. AB - We have succeeded in synthesizing a new type of totally artificial oxygen carrier which was produced by covering oil droplets (microsphere) with synthetic hemes (LH-M). We studied its oxygen-transporting ability in hemorrhagic dogs. Four beagles weighing about 8 kg were studied. Under controlled ventilation, exchange transfusion of 30 ml/kg was carried out. Cardiac output, hemoglobin and LH-M concentration in the blood, and blood gas were measured to 5 hours after intravenous injection of LH-M solution. LH-M delivered 15.7 to 22.3 ml/min (11 to 16%) of oxygen to the tissue and 5.5 to 8.2 ml/min (11 to 17%) of oxygen was consumed from LH-M to 5 hours after intravenous injection. Its half-life time in the blood stream was about 12 hours. It was confirmed that LH-M transported oxygen and released it to the tissue in vivo. PMID- 7994421 TI - The quality control of stroma-free hemoglobin: lysophosphatidylcholine, a component of stromal phospholipids, as candidate vasoconstrictive factor. AB - We characterized stromal phospholipids in stroma-free hemoglobin (SFH) by normal phase and cation-exchange HPLCs, and found that SFH contained not only four phospholipids which were the major constituent classes in membrane, but also several peaks which were not yet identified. The residual amounts of these lipids in SFH were changed with storage of red cell concentrates. The four major phospholipids decreased concomitantly with storage, whereas the unidentified peaks increased after 21 days and then decreased after 48 days. We also found that SFH contained lysophosphatidylcholine (LPC) at 5.71 micrograms/ml, which was the deacylated metabolite of phosphatidylcholine (PC). These results suggest that stromal phospholipids are degradable. Since LPC is known to be capable of producing a defect in endothelium-dependent arterial relaxation, we next examined the effect of stromal lipids on vascular tone in rabbit thoracic aortic strips. Preincubation with the crude lipid extract or the LPC purified from SFH by TLC significantly inhibited acetylcholine (ACh)-induced relaxation in phenylephrine (PhE)-precontracted tissues. These observations have led to the proposal that LPC, a component of stromal phospholipids, induces vasoconstriction as a result of inhibition of endothelium-dependent vasorelaxation. PMID- 7994422 TI - The sky is the limit. Interview by Mary Jane Zusy. PMID- 7994423 TI - World AIDS Day. PMID- 7994424 TI - Colors of the spectrum. Hospice nursing: a loving practice. PMID- 7994426 TI - Management perspectives. The nursing staff members on my unit feel that they are being asked to do too much. PMID- 7994427 TI - The Visiting Nurse Association of Washington, DC. PMID- 7994425 TI - The perils of rigor mortis thinking. PMID- 7994428 TI - Nursing in today's hectic home care environment. PMID- 7994429 TI - Pediatric epilepsy monitoring unit at Children's. PMID- 7994430 TI - Measurement of the quality of life. PMID- 7994431 TI - Anorectic medications in the treatment of obesity. PMID- 7994432 TI - Rural health. A broader perspective. PMID- 7994433 TI - What did the doctor do? When physicians and patients disagree. AB - OBJECTIVE: A serendipitous finding in a study of routine clinical encounters was that physicians and patients frequently gave discrepant reports of what had happened during a clinic visit. This report examines the conditions under which these discrepant perceptions occurred. DESIGN: Five experienced physicians and 189 patients completed postencounter questionnaires immediately following visits to an academic family practice clinic. After each encounter, the physician and patient estimated the duration of the visit and reported whether each of seven clinical events had occurred. RESULTS: The most common disagreements concerned whether the physician had provided counseling or performed a treatment procedure. Multiple regression analyses suggest that patient characteristics contributed to specific forms of physician-patient disagreement but that overall discrepancy was greatest in cases in which the physician minimized the importance of psychosocial issues and/or felt relatively confident about understanding the patient's problem. CONCLUSIONS: Although correlation need not imply causality, the results raise the possibility that physicians can promote shared physician-patient understanding by paying more attention to psychosocial factors and being more circumspect in drawing conclusions about patients' problems. PMID- 7994434 TI - Imported malaria in the 1990s. A report of 59 cases from Houston, Tex. AB - OBJECTIVE: To determine the frequency, the clinical features, and the response to therapy of imported malaria that was diagnosed in the 1990s in a major North American city. METHOD: A retrospective case series from Houston, Tex, of 59 cases of imported malaria presenting between January 1990 and April 1993. RESULTS: Malaria was diagnosed in 59 patients, consisting of 12 cases among patients who had acquired the infection while they were living in endemic areas prior to immigration to the United States, 32 cases among US residents who were originally from endemic areas, and 15 cases among patients originally from North America or Europe. Only 12 patients had received malarial prophylaxis: eight with chloroquine, one with chloroquine and chloroguanide (proguanil), two with chloroquine and primaquine, and one with mefloquine taken intermittently. Eight presented with Plasmodium falciparum infection after receiving chloroquine, and one, after receiving chloroquine and chloroguanide. Two presented with malaria caused by Plasmodium vivax despite receiving chloroquine and primaquine as prophylaxis. In 25 cases, malaria was not considered as an initial diagnosis. Five patients presented with severe disease (three with severe hemolysis, two each with cerebral malaria and renal failure, and one with adult respiratory distress syndrome). Four of the five had initially received a misdiagnosis. Two patients died despite treatment with intravenous quinidine and exchange transfusions. Two patients with P vivax infection had multiple relapses despite courses of chloroquine and primaquine. Six patients were pregnant (including one with a fatal case), one congenital infection was identified. Six patients had not traveled outside of the United States in over 1 year. CONCLUSION: Imported malaria occurs frequently and usually results from the failure to use appropriate prophylaxis. Delayed diagnosis and misdiagnosis are common. Severe disease and fatal cases continue to be seen despite aggressive treatment. Drug resistance has continued to spread and now occurs with P vivax as well as P falciparum. PMID- 7994435 TI - Prevalence of advance directives and do-not-resuscitate orders in community nursing facilities. AB - OBJECTIVE: To determine the prevalence of advance directives and do-not resuscitate (DNR) orders in nursing homes and to measure the effect of the Patient Self-Determination Act (PSDA) and patient characteristics on these prevalences. DESIGN: Cross-sectional study. SETTING: Eight rural community nursing facilities. PARTICIPANTS: Six hundred forty-one records of nursing home residents (total census of eight facilities). RESULTS: The mean age of the residents was 82.6 years and 75% were women. Thirty-seven percent were judged to have decisional capacity. Less than one third of the records revealed an advance directive (standard living will, 11.5%; other written directive, 11.1%; durable power of attorney for health care, 12%). Thirty-six percent had DNR orders. Residents with advance directives were older than those without them. Those residents with advance directives were more likely to have been admitted to the nursing home after the enactment of the PSDA (25.1% before vs 37.9% after enactment; P < .0001). There was substantial variation among facilities in both prevalences. Written rationales for DNR orders were found in only 40% of records. CONCLUSION: Enactment of the PSDA reflects increased interest in documentation of advance directives. However, in many nursing facilities, the prevalence of advance directives and DNR orders is relatively low. A greater commitment will be required by providers, residents, and their proxies if we are to change this reality. PMID- 7994436 TI - Injection granulomas. Intramuscle or intrafat? AB - OBJECTIVES: Intramuscular injection is a commonly used route of parenteral drug administration. We studied the fat vs muscle location, the depth of calcified buttock granulomas, and the thickness of subcutaneous fat. Data were assessed with respect to the length of a needle commonly used in intramuscular buttock injections. DESIGN: Three hundred thirty-eight sequential pelvic computed tomographic scans were studied. Subcutaneous fat thickness was measured for each patient at the upper outer quadrant of the buttock. The location and depth of each calcified granuloma were also recorded. SETTING: Tertiary care academic teaching hospital. RESULTS: One hundred sixty-four calcified granulomas were found in 67 patients. One hundred fifty-two of these granulomas were in fat and 12 were in muscle; this was statistically significant using a single-sample binomial distribution (P < .001;95% confidence interval, 0.04 to 0.13). The mean (+/- SD) subcutaneous fat thickness at the upper outer quadrant of the buttock was 5.0 +/- 1.9 cm, with female patients having a mean subcutaneous fat thickness of 5.7 +/- 1.8 cm vs 4.4 +/- 1.7 cm for male patients. CONCLUSIONS: The finding that buttock subcutaneous fat thickness exceeds the length of the most commonly used needle for intramuscular buttock injection (3.8 cm), together with the preponderance of calcified granulomas found in the fat of female patients, suggests that the currently used injection technique may not be therapeutically optimal. We suggest that longer needles be used for intramuscular buttock injections in adults. PMID- 7994437 TI - Alcohol and hypertension. AB - The link between alcohol and hypertension is well established, yet the mechanism through which alcohol raises blood pressure remains elusive. Possible mechanisms include an imbalance of the central nervous system, impairment of the baroreceptors, an increase of sympathetic activity, stimulation of the renin angiotensin-aldosterone system, an increase in cortisol levels, an increase of intracellular calcium levels with a subsequent increase in vascular reactivity, stimulation of the endothelium to release endothelin or inhibition of endothelium dependent nitric oxide production, and chronic subclinical withdrawal. For control of hypertension, cessation or at least reduction of alcohol intake is the first step. Pharmacologic treatment should be withheld until after 2 to 4 weeks of abstinence from alcohol. Alcoholism can result in autonomic neuropathy and cardiomyopathy that can lead to a fall in blood pressure. We believe that angiotensin-converting enzyme inhibitors and calcium channel blockers may be the most appropriate pharmacologic treatment. PMID- 7994439 TI - Cefuroxime axetil in the treatment of sinusitis. A review. AB - Cefuroxime axetil is a beta-lactamase-stable, second-generation, oral cephalosporin that penetrates sinus tissue in concentrations exceeding the MIC90 values (the minimum concentration of drug needed to inhibit the growth of 90% of an isolate of a particular microorganism) for pathogens most commonly associated with acute sinusitis, including Streptococcus pneumoniae and Haemophilus influenzae. A review of all clinical data published to date demonstrates that cefuroxime axetil has been evaluated in the treatment of acute sinusitis and acute exacerbations of chronic sinusitis ("acute-on-chronic sinusitis") in 18 clinical trials involving 1516 assessable patients. In 12 randomized, comparative trials, the rates of satisfactory clinical outcomes (cure or improvement, 79% to 100%) and bacteriologic eradication (84% to 100%) reported with the use of 250 mg of cefuroxime axetil twice daily were similar to those observed with the use of amoxicillin, amoxicillin/clavulanate potassium, cefaclor, cefadroxil, cefixime, clarithromycin, and doxycycline. In these comparisons, no antibiotic demonstrated any therapeutic advantages over cefuroxime axetil regarding time to symptom abatement. Cefuroxime axetil was at least as well tolerated as the other antibiotics. Overall, the role of cefuroxime axetil in the treatment of sinusitis appears to be as one of the broad-spectrum antibiotics that can be used for infections due to the most commonly implicated sinus pathogens, especially those due to the increasing number of relatively penicillin-resistant strains of S pneumoniae and beta-lactamase-producing strains of H influenzae and Moraxella catarrhalis. PMID- 7994440 TI - Poison ivy dermatitis. Nuances in treatment. AB - Acute allergic contact dermatitis due to poison ivy or poison oak is a common presenting complaint in the practices of many primary care physicians. While the clinical features are well described, reported treatment regimens vary in both topical and systemic therapies. We review herein the variability of presenting morphologic features of the disease and common treatment regimens, with attention given to complications of therapy. We also comment on the correct botanical designation, incidence, and immune mechanisms of the disease state and review measures to avoid allergic contact dermatitis due to poison ivy and poison oak. PMID- 7994438 TI - Rationale for the use of oral fluoroquinolones as empiric treatment of nursing home infections. AB - Despite relatively limited clinical data in nursing home patients, studies in non nursing home settings indicate that the systemic fluoroquinolones offer a spectrum of activity against typical gram-negative bacillary nursing home pathogens that is unavailable with other oral antimicrobials, offer excellent pharmacokinetics in the elderly, and have few adverse effects. When ofloxacin and ciprofloxacin have been compared with standard empiric intravenous or oral regimens in the hospitalized elderly in the treatment of the types of complicated urinary tract infections, pneumonia, and skin and soft-tissue infections that may be encountered in nursing homes, clinical efficacy has been at least equivalent. Although not similarly tested in nursing home settings, lomefloxacin, enoxacin, and fleroxacin have given clinical results at least comparable to control oral regimens for complicated urinary tract infection in the elderly. PMID- 7994441 TI - An inappropriate thyrotropin-secreting pituitary adenoma in a 30-year-old man. AB - Thyrotropin-secreting pituitary adenomas are rare, especially in the family practice setting. We report a case of such a tumor and review the literature. The key clinical finding is hyperthyroidism in the absence of a suppressed thyrotropin level. The patient was unusual in not having an elevated alpha subunit. All patients with hyperthyroidism should be screened for a thyrotropin level to rule out this unusual cause of hyperthyroidism. Other aspects of this case pertinent to primary care management are reviewed. PMID- 7994442 TI - Phentolamine reversal of epinephrine-induced digital vasospasm. How to save an ischemic finger. AB - A 17-year-old girl accidently injected her thumb with an adult autoinjector epinephrine syringe, resulting in rapid digital ischemia. Local infiltration of 0.5% phentolamine mesylate injected at the puncture site immediately resolved the ischemia and resulted in no long-term sequelae. Similar cases of epinephrine induced digital ischemia are reviewed herein, revealing phentolamine to be the drug of choice for reversal of this type of ischemia. Alternative attempts to restore blood flow included warm water immersion, amyl nitrite inhalations, metacarpal nerve block, and application of topical nitroglycerin paste; each was found to be ineffective. We conclude that digital ischemia secondary to accidental injection of epinephrine can be quickly and safely reversed with the use of 0.5% phentolamine locally infiltrated in the region of accidental injection. PMID- 7994443 TI - The kidney in hypertension--culprit or innocent bystander? PMID- 7994444 TI - Kidneys and primary hypertension--initiators, stabilizers or/and victim aggravators? AB - As the kidneys so importantly contribute to longterm blood pressure control, and decisively to e.g. Goldblatt hypertension, it is often assumed that they are "prime movers" also in most variants of primary hypertension. The "pros and cons" of such a view are briefly discussed, and not least because strategies in therapy and preventive measures in man greatly depend on the nature, and major sites of expression, of the polygenetic predisposition. It is emphasized how the predisposing elements usually seem to exert their main influences via decidedly extra-renal parts of cardiovascular control systems in general, though soon leading to secondary "upward resetting" of the renal barostat function concerning both salt-water excretion and the renal pressure-regulating hormones. In SHR, for example, all proximal systemic resistance vessels, including the renal preglomerular ones, show an intrinsic tendency towards structural upward resetting quite early in life. Further, already early common variants of human primary hypertension, as well as SHR, exhibit an evidently "primary" central hyper-reactivity to psychosocial stimuli. Via neuro-hormonal pressor and growth promoting effects such in principle extra-renal influences soon induce the same type of cardiovascular and renovascular structural upward resettings. Therefore the transfer of such kidneys to normotensive organisms here induces hypertension because of the prevailing preglomerular resistance increase, which easily gives the impression that these kidneys must have been the cause of hypertension in the donor organism as well.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7994445 TI - How much does the kidney participate in the origin of primary hypertension? AB - The existence of a relationship between the kidney and arterial hypertension has long been known. Renal participation in the development of arterial hypertension has been clearly shown in different animal models that mimic human essential hypertension. Different theories have tried to explain the mechanism(s) underlying the renal participation in human hypertension. According to the data contained in the literature renal vasoconstriction is present in the kidney since the very early stages of the hypertensive disease and could constitute the mechanism facilitating the development of arterial hypertension. PMID- 7994446 TI - Treatment of hypertension in the elderly (> or = 70 years). Recommendations from a Swedish-Norwegian expert group. PMID- 7994447 TI - Relation between low dose of hydrochlorothiazide, antihypertensive effect and adverse effects. AB - Thiazide diuretics are widely used in the drug treatment of hypertension but their dose-response curves for the antihypertensive and adverse metabolic effects differ. To characterize the lower end of the dose-response curve a double-blind, parallel group trial was performed as multicentre study in Scandinavia. One hundred and eleven patients with newly diagnosed or previously treated mild to moderate hypertension (untreated diastolic blood pressure of 95-115 mmHg after 4 weeks placebo) were randomly allocated to various doses of hydrochlorothiazide (3, 6, 12.5 or 25 mg) or placebo for 6 weeks. Blood pressure and biochemical variables (plasma renin activity, serum potassium, magnesium, urate, fasting glucose, total cholesterol, HDL-cholesterol, triglycerides and apolipoproteins A1 and B were measured. 12.5 mg hydrochlorothiazide had a borderline effect on blood pressure whilst 25 mg had a definite antihypertensive effect. Biochemical changes were seen in plasma renin activity, serum potassium and urate after the 12.5 and 25 mg dose. Three and 6 mg had no effect on blood pressure or metabolic parameters. PMID- 7994448 TI - Hemodynamic and humoral effects of low-dose aspirin in treated and untreated essential hypertensive patients. AB - Aspirin at low doses is used as an inhibitor of platelet aggregation and is frequently administered to essential hypertensive patients with arterial thrombotic complications. However, it is unknown whether aspirin can modify blood pressure values either in treated or untreated hypertensive patients, as described for other non steroidal anti-inflammatory drugs. Thus 30 patients. 10 with mild uncomplicated and untreated essential hypertension, 10 with essential hypertension under chronic treatment with captopril, 50 mg bid, and 10 with essential hypertension under chronic treatment with atenolol, 100 mg oid, received aspirin, 100 mg oid, and the corresponding placebo for one month, according to a double blind randomized cross-over design. At the end of each treatment, blood pressure, heart rate, generated serum thromboxane B2 and urinary excretion of thromboxane B2 and 6 keto prostaglandin F1 alpha and plasma renin activity were measured. Both in treated and untreated essential hypertensive patients, aspirin administration did not affect blood pressure, heart rate and urinary 6 keto prostaglandin F1 alpha, while it significantly reduced serum and urinary excretion of thromboxane B2 and plasma renin activity. In conclusion, while the present data confirm that low doses of aspirin selectively inhibit thromboxane B2 synthesis, they indicate that aspirin at 100 mg oid can be administered to treated and untreated essential hypertensive patients without any harmful effect on blood pressure values. PMID- 7994449 TI - The effects of alpha-trinositol on haemodynamic variables and neuropeptide Y levels in a pilot study of hypertensives and healthy volunteers. AB - AIMS: The aim of this study was to examine the effects of D-myo-inositol-1,2,6 trisphosphate (alpha-trinositol) on haemodynamic variables and neuropeptide Y (NPY) levels in hypertensives and healthy volunteers. METHODS: Hypertensives (n = 13) and normotensives (n = 11) were recruited after a screening of cardiovascular risk factors of all men aged 40 living in a well defined area. The hypertensives were previously unmedicated. The effect of alpha-trinositol was studied after intravenous infusion at rest, and during and after a maximal exercise test in a double-blind crossover manner with placebo. RESULTS: Haemodynamic variables and NPY levels were recorded. NPY levels did not differ between normotensives and mild hypertensives at the start of the study. However, a significant increase was seen in hypertensives after they had risen to the sitting position. During exercise, the NPY levels increased significantly both in normotensives and hypertensives. After the exercise test, the NPY levels were significantly higher in hypertensives than in normotensives; alpha-trinositol did not modify these responses. In normotensives no significant difference in systolic blood pressure was seen during or after the exercise test whether they were on alpha-trinositol or placebo. In the hypertensives on active drug, however, the blood pressure tended to be approximately 5 mmHg lower during the exercise test as compared with the placebo group. In the hypertensives on active drug, the heart rate increased significantly more during exercise as compared with the placebo groups. In normotensives, the same tendency was seen, but it did not reach statistical significance. CONCLUSIONS: The NPY antagonist, alpha-trinositol, tends to reduce the increase in systolic blood pressure induced by maximal exercise and increases the heart rate in hypertensives but not in normotensives. PMID- 7994450 TI - The BBB Study: the effect of intensified antihypertensive treatment on the level of blood pressure, side-effects, morbidity and mortality in "well-treated" hypertensive patients. Behandla Blodtryck Battre. AB - The BBB study (Swedish for Behandla Blodtryck Battre or Treat Blood Pressure Better) was a multicenter trial designed to investigate three aspects of antihypertensive treatment: i) Is it possible to lower the diastolic blood pressure further in "well-treated" hypertensive patients through intensified therapy? ii) Can this aim be fulfilled without increasing the incidence or severity of side-effects? iii) If i) and ii) can be answered in the affirmative, will the further reduction in diastolic blood pressure be associated with a further reduction in hypertension-associated mortality and morbidity? Altogether 2127 hypertensive men and women with an average age of 59.8 years (46-71) were recruited at 142 primary health care centers in Sweden. Approximately 10,000 patient-years were accumulated. All patients had treated essential hypertension and all had diastolic blood pressures in the range 90-100 mmHg on three consecutive visits before entering the study. The patients were randomized to either intensified treatment aiming at a blood pressure < or = 80 mmHg diastolic (group A) or to unchanged therapy (group B). A difference between group A and group B in diastolic blood pressure of 7-7.5 mmHg was achieved for > 4 years. Adverse effects were studied in detail in 100 randomly selected patients from each group using a special questionnaire and a visual analogue scale. The adverse effect score fell significantly in group A but remained unchanged in group B. Regarding cardiovascular morbidity and mortality there were no significant differences between groups A and B, the total number of strokes and myocardial infarcts being 28 in group A and 29 in group B.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7994451 TI - The influence of coarctation hypertension on the pharmacodynamic behaviour of rat isolated conduit vessels. AB - We have studied the effects of coarctation hypertension on the reactivity of the aorta with respect to alpha 1-adrenoceptor mediated vasoconstriction and methacholine-induced endothelium-dependent vasodilation. The experiments were performed in aortic rings taken from rats that had been subjected to banding of the abdominal aorta, aortic stenosis rats (ASR), and from SHAM operated control rats. As expected, the thoracic aorta was subjected to elevated blood pressure, whereas the pressure in the abdominal aorta region was much lower. Concomitantly, the thoracic and abdominal aorta regions were studied separately as isolated vessels. Both the thoracic and abdominal aortic rings taken from ASR were more sensitive to phenylephrine than those obtained from control rats. The increase in sensitivity cannot be explained by elevated pressure alone and neurohormonal factors are likely to play a role. The maximal relaxation induced by methacholine in thoracic aortic rings obtained from ASR was significantly less when compared with that in preparation taken from SHAM rats. No changes in maximal relaxation were observed in the abdominal aortic rings. It is concluded that i) the enhanced responsiveness of the rat aorta to alpha 1-adrenoceptor stimulation cannot be explained by elevated blood pressure alone and ii) coarctation hypertension impairs the endothelium-dependent relaxation of the aortic region exposed to high blood pressure. PMID- 7994452 TI - Formation of des-Asp-angiotensin I in the hypothalamic extract of normo- and hypertensive rats. AB - Exogenous angiotensin I (ANG I) was degraded to mainly des-Asp-ANG I instead of ANG II in the hypothalamic homogenate of the Sprague Dawley (SD), Wistar Kyoto (WKY), left renal artery stenosed hypertensive SD (LRAS), deoxycorticosterone acetate/salt-induced hypertensive SD (DOCA-salt) and spontaneously hypertensive rats (SHR). In the same homogenate, ANG II was degraded to ANG III and ANG III remained unchanged during the first 10 min of incubation. However, all the homogenates were able to catalyse hippuryl-L-histidyl-L-leucine to hippuric acid and the catalysis was completely inhibited by 3 microM captorpil. The data show that the angiotensin converting enzyme present in the hypothalamus when extracted by the normal laboratory procedures is not able to hydrolyse ANG I to ANG II. In addition, the aminopeptidase that degraded ANG I to des-Asp-ANG I was not inhibited by amastatin, bestatin and EDTA, indicating that it is not aminopeptidase A or B. The formation of hippuric acid was significantly higher in the homogenate of the LRAS whilst the SHR and DOCA-salt showed significant higher rate of des-Asp-ANG I formation than in the normotensive control rats. PMID- 7994454 TI - Hypertension, the logic of definitions. PMID- 7994453 TI - Differential regulation of brain angiotensin II in genetically hypertensive and normotensive rats after nephrectomy. AB - To investigate the role of tissue angiotensin II (Ang II) in the maintenance of hypertension after nephrectomy in spontaneously hypertensive rats (SHR), Ang II levels were measured in various tissues of both 12-week-old SHR and normotensive control, Wistar-Kyoto rats (WKY), 48 h after nephrectomy or sham operation. Ang II was determined by radioimmunoassay coupled with high performance liquid chromatography. Nephrectomy caused a decrease of plasma renin activity and plasma Ang II concentration in both SHR and WKY. Aortic Ang II levels were significantly lowered by nephrectomy only in WKY, and not in SHR. Ang II levels in hypothalamic block, brainstem and cerebellum of SHR increased after nephrectomy, whereas those of WKY were unchanged. Intracerebroventricular administration of ceronapril, an angiotensin converting enzyme inhibitor, significantly decreased sustained high blood pressure in SHR 48 h after nephrectomy compared with vehicle administration, whereas intravenous administration had no effect. These results suggest that in spite of the important role of the renal renin-angiotensin system in maintenance of high blood pressure in SHR, control mechanisms may switch to other systems after nephrectomy, and that the increased brain Ang II levels after nephrectomy may be related to these mechanisms. PMID- 7994455 TI - Intercultural reasoning: the challenge for international bioethics. PMID- 7994456 TI - Outside the Garden of Eden: rural values and healthcare reform. PMID- 7994457 TI - Cultural aspects of nondisclosure. PMID- 7994458 TI - African American suspicion of the healthcare system is justified: what do we do about it? PMID- 7994459 TI - C-sections as ideal births: the cultural constructions of beneficence and patients' rights in Brazil. PMID- 7994460 TI - Conflicts between Chinese traditional ethics and bioethics. PMID- 7994461 TI - CQ sources. PMID- 7994462 TI - Telling the truth to patients: a clinical ethics exploration. PMID- 7994463 TI - Distributive justice and the regulation of fertility centers: an analysis of the Fertility Clinic Success Rate and Certification Act. PMID- 7994464 TI - Anchor and course for the modern ship of casuistry. PMID- 7994465 TI - It is time to emerge from the trench and survey the whole battlefield. PMID- 7994466 TI - Advance directives: a question of autonomy. PMID- 7994467 TI - The Patient Self-Determination Act and cultural diversity. PMID- 7994469 TI - Patient Self-Determination Act: an African American perspective. PMID- 7994468 TI - Patient Self-Determination Act: a Hispanic perspective. PMID- 7994470 TI - Patient Self-Determination Act: a Native American (Navajo) perspective. PMID- 7994471 TI - Request from a Middle Eastern Bride. PMID- 7994472 TI - Multiculturalism, medicine, and the limits of autonomy: the practice of female circumcision. PMID- 7994473 TI - Joseph J. Jacobs on alternative medicine and the National Institutes of Health. Interview by Thomasine Kushner and Charles MacKay. PMID- 7994474 TI - Casuist or Cassandra? Two conceptions of the bioethicist's role. PMID- 7994475 TI - The educational needs of ethics committees. PMID- 7994477 TI - Vestibular bibliography. PMID- 7994476 TI - Consultants and committees: a cooperative and mutually educational enterprise. PMID- 7994478 TI - Saccadic dysmetria is similar in patients with a lateral medullary lesion and in monkeys with a lesion of the deep cerebellar nucleus. AB - Some of the clinical hallmarks of lateral medullary infarction--Wallenberg's syndrome--are saccadic dysmetria, smooth pursuit deficit, and lateropulsion of the body. Similar movement disorders are seen in monkeys after local unilateral injection of GABAergic drugs in the caudal fastigial nucleus of monkeys. These include an ipsilateral saccadic hypermetria and a contralateral saccadic hypometria as well as cogwheel smooth pursuit eye movements toward the contralateral side and an ipsiversive lateropulsion of the body. It was previously suggested that the lateral medullary infarction causes a lesion of climbing fibers to the cerebellum. This lack of climbing fiber input increases the activity of ipsilateral Purkinje cells, which consequently provide too much inhibition of the deep cerebellar nuclei. PMID- 7994479 TI - Evidence suggesting individual ocular motor control of each eye (muscle). AB - Current models of the ocular motor system are usually presented in their most reduced form, are unilateral in architecture, and precise yoking is presumed. Although this simplifies the models, it does not accurately simulate the actual neuroanatomy and limits the models to simple, stereotyped responses. Studies of normal humans and monkeys have demonstrated striking disconjugacies in normal responses. Normal saccades may be disconjugate, or 1 eye may exhibit a dynamic overshoot. Asymmetric vergence can result in disconjugate saccades, unequal magnification spectacles cause differential saccadic gain adjustment, and saccades to unequal disparities also cause unequal saccades in the 2 eyes. In strabismus, deviated eyes typically do not mimic the movements of the fixating eye nor do their latent or congenital nystagmus waveforms duplicate those of the fixating eye. In spasmus nutans, each eye oscillates independently of the other. In achiasmatic dogs, uni-ocular saccades and uni-ocular nystagmus waveforms are seen; the same may be true in human achiasma. These data from both normals and those with abnormalities suggest that current models for ocular motor control are inadequate representations of the actual system. The inability of unilateral, yoked control (or even bilateral, yoked control) system models to duplicate the ocular motor responses of binocular mammals suggests that their ocular motor systems evolved from the bilateral, independent control systems seen in chameleons. One need only postulate a yoking overlay superimposed on two independent control systems to achieve conjugacy (bilateral, yoked, independent control) of the eyes. Abnormalities producing grossly disconjugate eye movements may then be simulated using the independent control of each eye released by a deficiency in the yoking overlay. Independent control of each eye coupled with the essential bilateral brain stem architecture implies that each individual muscle is driven by independent populations of neurons (burst cells, neural integrator cells, etc.). The agonist muscles of each eye are usually coordinated (yoked) but may function independently if the task dictates or if binocularity did not develop. Models based on the above architecture would be robust and could duplicate the many responses (both normal and abnormal) possible from the neurophysiological system. PMID- 7994480 TI - Supplementation of the human vestibulo-ocular reflex by visual fixation and smooth pursuit. AB - In studies over the past 30 years, D. A. Robinson and colleagues established that the dynamic characteristics of smooth pursuit eye movements (SP) are different at the onset from those at the cessation of the response. They proposed that cessation of SP was due to a separate fixation system. During head movements, both fixation and SP may contribute to gaze stabilization. We investigated the relative contributions of fixation and SP to the "visually enhanced" vestibulo ocular reflex (VVOR) using a paradigm requiring a transition from VVOR to combined eye-head tracking (CEHT). We found, in four normal subjects, that ringing typical of SP generally did not occur during VVOR, but that it often appeared after the transition to CEHT. The findings were different in two patients with absent peripheral vestibular function; ringing typical of SP occurred always during VVOR but disappeared during the onset of CEHT. These results can be explained by a model in which an internal representation of target velocity serves as input to parallel SP and fixation systems, and as the determinant of which of the two systems will provide the command signal. Interpretation of our data using this model indicates that either fixation or SP systems may "visually enhance" the VOR, depending on the magnitude of retinal error velocity that remains after vestibular eye movements have been generated. PMID- 7994481 TI - Effect of aging on vertical visual tracking and visual-vestibular interaction. AB - We investigated the effect of aging on vertical smooth pursuit, small-field optokinetic nystagmus (OKN), the vestibulo-ocular reflex (VOR), and visual vestibular interactions (VVI). Telescopic spectacles were used to magnify the visual effects of head movements and accentuate the demand on VVI. Eleven normally sighted young subjects (age 30 +/- 6 y, mean +/- SD), and 9 normally sighted elderly subjects (age 70 +/- 8 y) were studied. Three types of stimulus motion were used: 1) predictable single sinusoidal frequencies from 0.8 to 3.2 Hz, 2) poorly predictable motion consisting of a sum of multiple harmonics of a 0.4 Hz fundamental, and 3) unpredictable velocity impulses. Tracking gains declined with frequency and stimulus unpredictability but were always greater for young than elderly subjects. Pursuit gain was always less than OKN gain for subjects tested under comparable conditions of frequency and velocity. In both subject groups, pursuit and OKN tracking exhibited phase lags at higher frequencies, particularly for poor predictable motion. Tracking phase lags were greater for pursuit than OKN and were consistently greater in the elderly than in young subjects. In young subjects, stimulus dimming using a 2 log neutral density filter reduced tracking gains and increased phase lags. In both young and elderly subjects, VOR gain was < 1.0 at low frequencies and increased slightly with increasing frequency. Visually enhanced VOR gain during normal vision was the ideal value of 1.0 at all frequencies in both subject groups. During wearing of telescopic spectacles, the young subjects exhibited marked gain enhancement that was greatest at lower frequencies and greater during predictable than unpredictable motion. Young subjects were able to suppress the VOR by fixation of real or imaginary targets moving with the head; this suppression was better at the lowest frequencies and for predictable motion. Phase errors were substantial for significant VVI in young subjects but were minimal in the elderly. Visual enhancement of VOR gain, as well as suppression by real and imaginary head-fixed targets, were attenuated in the elderly subjects. During rotations in which young subjects wore 4x telescopic spectacles, 2 log unit dimming of the visual environment reduced gain and increased phase lags. The deficiencies in VVI exhibited by elderly subjects are attributable both to deficits in the visual tracking component, as well as to nonvisual mechanisms, because even changes in mental set are less effective in modifying gain in older subjects.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7994482 TI - Modeling slow correcting gaze movements. AB - Recent experimental results show evidence for the corrective role of postsaccadic drifts. This paper addresses the modeling of these slow correcting gaze movements (SCMs). Classical arguments to explain drifts are presented, both in the head fixed condition (pulse-step mismatch) and in the head free condition (vestibulo ocular reflex (VOR)). The most significant behavioral and electrophysiological experimental data related to SCMs are then briefly reported, with the conclusion that SCMs have a clear corrective role, incompatible with classical explanations of drifts. Based on these experimental data, existing models of the saccadic system are then compared. A theoretical comparison of the classical Robinson model with an alternative model is proposed. Two possible (slow and fast) pathways involved in the control of SCMs are examined, and simulation results are presented. Finally, the discussion addresses the observed species differences in SCMs. The link between natural SCMs and electrical SC stimulations, and the interactions between saccades, VOR, and SCMs are also discussed. PMID- 7994483 TI - Model of coupled or dissociated eye-head coordination. AB - Tight coupling between eye and head movements have been observed in response to a single visual target offset or a single flash. On this basis, when the visual stimulus consists of two successive steps or flashes in the same (horizontal) direction, either increasing in eccentricity or decreasing in eccentricity, gaze should be due to concomitant eye and head angular displacement. The main findings were that in response to increasing eccentricity stimulus, the majority of the gaze movement had a staircase pattern, and to decreasing eccentricity stimulus, a pulse-step pattern. Some responses were one gaze movement to the final target (or flash) offset. In all these responses, eye and head were tightly coupled. In some cases, however, in response to two flashes or two successive steps decreasing in eccentricity, the initial eye and head movements were dissociated: eye and head were directed to different offsets. Current eye-head models assume a strong coupling between the head displacement and the eye saccade. We have modified the Laurutis and Robinson model to accommodate the new findings of saccade-VOR cooperation and eye-head dissociated responses. we suggest that when gaze falls short of the target offset, the retinal error signal is not only fed to the saccadic system but also partially suppresses the VOR gain control. This allows for "corrective VOR" movements after the gaze saccade has occurred.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7994484 TI - Eye position signals in the vestibular nuclei: consequences for models of integrator function. AB - Recordings from neurons in the vestibular nuclei indicate that the cells that carry eye position signals encode the position of a single eye (either ipsilateral or contralateral) during both conjugate and vergence eye movements. The fact that the vestibular nuclei are aware of the positions of each eye is not surprising as the otolith-based linear vestibulo-ocular reflex is known to change its behaviour as a function of uniocular eye position. This result suggests that the signal coming from the oculomotor velocity-to-position integrator specifies the position of each eye during vergence movements and thus must receive a vergence velocity input along with its conjugate velocity inputs. As there is no vergence system in laterally eyed animals, we have proposed two possible models of integrator arrangement that could have developed from conjugate directional (rather than uniocular) integrators in lower animals without frontally mounted eyes. Both of these models explain the existence of near-response cells and produce the required bidirectional gaze paretic nystagmus following unilateral lesions of one integrator. The models also make specific and different predictions concerning the effects of unilateral integrator lesions on the behaviour of the vergence system and thus make suggestions for further experiments. PMID- 7994485 TI - Eye position signals in the abducens and oculomotor nuclei of monkeys during ocular convergence. AB - Many neurons in oculomotor pathways encode signals related to eye position. For example, motoneurons in the third, fourth, and sixth cranial nuclei discharge at highly regular rates during fixation intervals. During fixations of far targets, their tonic discharge is linearly related to conjugate eye position. Previous studies provided evidence that premotor cells in brainstem pathways also encoded conjugate eye position. McConville et al. (this volume), however, measured eye movements during binocular fixations when the eyes were converged and concluded that the position signal encoded by premotor position-vestibular-pause (PVP) cells in the vestibular nuclei is related to monocular (right or left) eye position rather than to conjugate eye position. This surprising relationship would not have been noticed in earlier studies that measured the movements of only one eye (using a single eye coil) or that measured only the conjugate movements of the two eyes (using bitemporal EOG electrodes). How general a feature of oculomotor signal processing is this finding? In this paper, we re examine the eye position signal in abducens and oculomotor neurons when the movements of the two eyes are conjugate and when they are disjunctive and therefore disassociated. The data suggest that abducens neurons (AMNs and AINs) and oculomotor neurons (putative medial rectus motoneurons), unlike PVP cells, are not monocular but encode mixtures of right and left eye position signals. PMID- 7994486 TI - Laser and tandem scanning confocal microscopic studies of rabbit corneal wound healing. AB - The process of corneal endothelial wound healing was studied using laser and tandem scanning confocal microscopy (LSCM and TSCM). Following transcorneal freeze (TCF) injury, rabbit corneas were observed using ex vivo LSCM and in vivo TSCM. LSCM revealed the intracellular actin filament organization which, stained with phalloidin-FITC, in migrating endothelial cells, transformed fibroblast-like cells, stroma keratocytes, and epithelial cells during wound healing in corneal tissue. The TSCM provided sequential spatial observation of morphologic changes from endothelium to epithelium of the cornea during in vivo cellular repair of wound healing noninvasively on the same cornea without animal sacrifice. Ex vivo LSCM supported the morphologic analysis of the in vivo TSCM observations. PMID- 7994487 TI - Real-time confocal microscopy of keratocyte activity in wound healing after cryoablation in rabbit corneas. AB - A modified tandem scanning confocal microscope was used for real-time in vivo examination of the rabbit cornea following a cryogenic injury. The corneas of New Zealand white rabbits were frozen with a probe that had been cooled by immersion in liquid nitrogen, effectively destroying keratocytes in a central 5 mm diameter zone throughout the total thickness of the cornea. In these eyes, keratocyte repopulation and corneal stromal wound healing proceeded similarly to that which occurs after epikeratophakia, a refractive surgical procedure designed to change the curvature and optical power of the cornea. In epikeratophakia, a cryolathed donor corneal stroma lenticule is sutured onto the bare stroma of the recipient cornea. The collagen tissue lenticule is repopulated by keratocytes (corneal fibroblasts) that migrate in from the host cornea. In our study, the confocal microscope permitted sequential, noninvasive examination of the corneal stroma in the treated animals. Necrosis of the keratocytes, followed by activation of the remaining viable cells in the corneal periphery, was observed in the first 2 to 3 days after cryo injury. A fine stromal fibrous network was seen to develop; in three eyes, this network progressed to the development of a retrocorneal fibrous membrane and dense stromal fibrosis, both of which resulted in significant loss of corneal clarity. Our results suggest that the confocal microscope may be a valuable tool to provide much needed information on wound healing processes at the cellular level after corneal surgery and injury. PMID- 7994488 TI - The intracellular distribution of vinculin and alpha 2 integrin in epithelial cells and chondrocytes. AB - The purpose of this study was to demonstrate the presence of vinculin and alpha 2 integrin in chondrocytes in situ and epithelial cells. We also determined that the appropriate fixation and extraction protocols for immunohistochemistry and laser scanning confocal microscopy for an integral membrane protein and an actin associated protein in cultured cells and whole tissue was different. Cultured epithelial cells, whole mount human cornea and avian cartilage were fixed and prepared using a number of standard procedures used for indirect fluorescence immunohistochemistry. The distribution of vinculin was cell-type and fixation specific. Chondrocytes and cultured epithelial cells demonstrated vinculin in areas that appear to be associated with filamentous actin. Vinculin was associated with cell membranes in human cornea. The expression of alpha 2 integrin observed in chondrocytes fixed with methanol, paraformaldehyde, or formaldehyde is consistent with its role in cell-substrate interaction, but may also suggest a role in dividing and differentiating cells. The localization of alpha 2 integrin in human corneal epithelia supports its role as a cell-cell adhesion molecule. The cytoplasmic distribution of vinculin and alpha 2 integrin in tissues fixed without detergent extraction suggests that the fixation step may be sufficient for antibody penetration and antigen extraction. These studies are the first report of vinculin and alpha 2 integrin in embryonic chondrocytes. In addition we have shown that confocal laser scanning microscopy combined with proper fixation and extraction protocols may optimize the localization of antigens in cultured and whole mount cells. PMID- 7994489 TI - High temporal and spatial resolution studies of bone cells using real-time confocal reflection microscopy. AB - Chick and rat bone-derived cells were mounted in sealed coverslip-covered chambers; individual osteoclasts (but also osteoblasts) were selected and studied at 37 degrees C using three different types of high-speed scanning confocal microscopes: (1) A Noran Tandem Scanning Microscope (TSM) was used with a low light level, cooled CCD camera for image transfer to a Noran TN8502 frame store based image analysing computer to make time lapse movie sequences using 0.1 s exposure periods, thus losing some of the advantage of the high frame rate of the TSM. Rapid focus adjustment using computer controlled piezo drivers permitted two or more focus planes to be imaged sequentially: thus (with additional light source shuttering) the reflection confocal image could be alternated with the phase contrast image at a different focus. Individual cells were followed for up to 5 days, suggesting no significant irradiation problem. (2) Exceptional temporal and spatial resolution is available in video rate laser confocal scanning microscopes (VRCSLMs). We used the Noran Odyssey unitary beam VRCSLM with an argon ion laser at 488 nm and acousto-optic deflection (AOD) on the line axis: this instrument is truly and adjustably confocal in the reflection mode. (3) We also used the Lasertec 1LM11 line scan instrument, with an He-Ne laser at 633 nm, and AOD for the frame scan. We discuss the technical problems and merits of the different approaches. The VRCSLMs documented rapid, real-time oscillatory motion: all the methods used show rapid net movement of organelles within bone cells. The interference reflection mode gives particularly strong contrasts in confocal instruments. Phase contrast and other interference methods used in the microscopy of living cells can be used simultaneously in the TSM. PMID- 7994490 TI - In vivo observation of the corneal epithelium. AB - Specular microscopy is an important addition to the ophthalmologist's diagnostic armamentarium. Using this technique, it has been found that normal corneal epithelial cells are polygonal, with no abnormal specular reflex. There are no spindle-shaped, large or small cells, as may be observed in a variety of pathologic conditions. Spindle-shaped cells are characteristic of the wound healing process with cell migration. Large cells were observed not only in wound healing, but also in aphakic diabetic patients, extended-wear soft contact lens wearers, and individuals with keratoconus. These changes may result from depressed mitosis or inhibited sloughing of superficial cells. Morphometric analysis adds a quantitative dimension to epithelial cell analysis. PMID- 7994491 TI - The use of confocal microscopy in evaluating corneal wound healing after excimer laser keratectomy. AB - Corneal wound healing following excimer laser keratectomy is the major cause of regression of treatment results. The amount of anterior stromal haze that develops may be influenced by topical medications. Over a period of 6 months, we followed 15 New Zealand white rabbit eyes that underwent excimer laser keratectomy with the VISX 193-nm ArF laser at a fluence of 150 mJ/cm2 for a depth of 130 microns. Eyes were randomized to treatment with prednisolone acetate, diclofenac sodium (Voltaren), a combination of both, and a control group. Drops were administered four times a day for 1 week, two times a day for 3 weeks, and the drops were then tapered. All eyes were reepithelialized by 5 to 7 days. The tandem scanning confocal microscope (TSCM) was used to evaluate the corneal wound in vivo weekly for a month and monthly for 6 months. During the early postoperative period, the TSCM revealed significant anterior stromal keratocyte activation with cell elongation and the spindle-shaped appearance of fibroblasts in all groups. Collagenous stromal scarring was evident initially, then slowly decreased in all treatment groups. This study shows that TSCM is clinically useful for successive in vivo examinations of corneal wounds after excimer laser keratectomy and for comparing the effects of various topical medications. PMID- 7994492 TI - Observations of human corneal epithelium by tandem scanning confocal microscope. AB - We applied the tandem scanning confocal microscope (TSCM) to 30 healthy human corneas of 3 normal volunteers and 27 patients with cataract and retinal detachment to observe normal corneal epithelial cells in vivo. All corneas were normal under slit lamp microscopic examination. The superficial and basal epithelial cells close to the basal lamina in the central cornea were recorded on videotape and analyzed by a computer-assisted digitizer. The mean cell areas of superficial cells exposed at the surface and basal cells at the horizontal section were 624 +/- 109 microns2 and 66 +/- 5 microns2, respectively. The ratio of superficial to basal mean cell area was 11.0 +/- 4.5. TSCM was thus useful in evaluating the relationship between superficial and basal cells in human corneal epithelium in vivo. PMID- 7994493 TI - Limitations in tandem scanning confocal microscopy as a diagnostic tool for microbial keratitis. AB - One potential application of tandem scanning confocal microscopy is the detection of in vivo pathogens. Our study of an experimental model of Acanthamoeba keratitis demonstrates that while this technology can successfully detect certain organisms, there are currently limitations. These limitations relate to instrument configuration, movement of either the tissue or the microscope, difficulty in reproducibly returning to the area of interest for serial examination, the lack of a distinctive morphology of some pathogens, and limited resolution of the microscope. PMID- 7994494 TI - Confocal microscopy of corneal penetration by tarantula hairs. AB - In vivo identification of foreign bodies in the cornea may be impossible if the size and/or location precludes visualization by slit lamp biomicroscopy, which has an upper limit of magnification of 50x. These limitations became obvious when we attempted to identify the offending material in the inflamed eye of a patient who complained of foreign body sensation after contact with a pet tarantula. As a model of this clinical situation, we used a newly developed tandem scanning confocal microscope to observe and to photograph tarantula hairs as they penetrated the corneal stroma and endothelium and entered the anterior chamber in rabbit eyes. We found that, experimentally, the hairs penetrated the ocular tissues apparently without inciting inflammation or causing fibrosis. The instrument we used--a prototype with a Nipkow disk from Noran, Inc. (Middleton, Wis.) and a 25/0.8 na glycerin immersion lens (Plan-Neofluor, Zeiss)--provides magnifications of 100-500x, real-time viewing in vivo, optical sectioning, contrast control, high resolution, processing through image analysis systems, and video and hard copy output. We believe that confocal microscopy offers a new approach to the identification and localization of foreign bodies in the anterior segment, as well as to the visualization and diagnosis of ocular diseases, including bacterial, fungal, and other parasitic invasions, in the human eye. PMID- 7994495 TI - In vivo observation of the human tear film by tandem scanning confocal microscopy. AB - A new method for observing normal and pathologic states of the human tear film using tandem scanning confocal microscopy is presented. The confocal microscope is configured with a horizontal light path, a 10 x dry objective, and an image intensified camera for collecting images at a magnification of approximately 150x. The advantages of confocal microscopy can be used to collect reflected images of the human tear film with improved detail and resolution. PMID- 7994496 TI - Implications of historical evidence for the classification of eating disorders. A dimension overlooked in DSM-III-R and ICD-10. PMID- 7994497 TI - Needs assessment. Involvement of staff and users will help to meet needs. PMID- 7994499 TI - Merycism or rumination disorder. A historical investigation and current assessment. AB - BACKGROUND: In the 'fashionable' field of eating disorders, there has been a notable gap in the historiography of rumination, allowing considerable scope for constructing a comprehensive historical profile of this disorder. METHOD: A wide ranging examination of printed material, both etymological and medical, backed by a Medline computer search, uncovered extensive sources, some of considerable rarity, including case reports from the early 17th century onwards. Extracted data focused on incidence, sex distribution, age range, outcome and causation, and the findings are discussed in relation to diagnostic criteria in DSM-III-R and ICD-10. RESULTS: While confirming the frequency of rumination in infants and the mentally retarded, the study demonstrated, particularly, the need to recognise its occurrence in normal adults, occasionally as a collateral behaviour in anorexia and bulimia nervosa, and suggested that its prevalence, distorted by secrecy, exceeded estimated levels. CONCLUSIONS: In future reviews of classification, existing anomalies and inadequacies in the status and description of rumination would benefit from integrating some of the historical conclusions. PMID- 7994498 TI - Psychiatry and the concept of evil. Sick in heart or sick in mind? PMID- 7994500 TI - Cognitive therapy, analytic psychotherapy and anxiety management training for generalised anxiety disorder. AB - BACKGROUND: We test the hypotheses that (a) cognitive therapy is of comparable efficacy to psychodynamic psychotherapy, (b) 8-10 sessions of therapy is as effective as 16-20 sessions, and (c) brief therapist training is as effective as intensive training. METHOD: Of 178 out-patients referred to a clinical trial of psychological treatment for generalised anxiety, 110 patients met DSM-III-R criteria for generalised anxiety disorder and were randomly assigned to three different forms of psychotherapy. The main comparison was between cognitive therapy and analytic psychotherapy, delivered by experienced therapists at weekly or fortnightly intervals over six months. A third treatment, anxiety management training, was delivered at fortnightly intervals by registrars in psychiatry after a brief period of training. Eighty patients completed treatment and were assessed before treatment, after treatment, and at six-month follow-up. RESULTS: Cognitive therapy was significantly more effective than analytic psychotherapy, with about 50% of patients considerably better at follow-up. Analytic psychotherapy gave significant improvement but to a lesser degree than cognitive therapy. There was no significant effect for level of contact. Patients receiving anxiety management training showed similar improvements to cognitive therapy after treatment, with rather lower proportions showing clinically significant change. CONCLUSIONS: Cognitive therapy is likely to be more effective than psychodynamic psychotherapy with chronically anxious patients. Significant improvements in symptoms can be achieved by trainee psychiatrists after only brief instruction in behaviourally based anxiety management. However, the superiority of cognitive therapy at follow-up suggests that the greater investment of resources required for this approach is likely to pay off in terms of more sustained improvement. There is no evidence that 16-20 sessions of treatment is more effective, on average, than 8-10 sessions. PMID- 7994502 TI - Depression in Parkinson's disease. A positron emission study. AB - BACKGROUND: This study investigated biological correlates of depression in patients with idiopathic Parkinson's disease (PD). We tested the hypothesis that in patients with PD and depression, there was regional dysfunction involving brain areas previously implicated in functional imaging studies of patients with primary depression. METHOD: Using positron emission tomographic measurements of regional cerebral blood flow (rCBF), patterns of resting rCBF were measured in ten patients with PD and major depression, and ten patients with PD alone. The results were compared with findings from ten patients with primary depression and ten normal controls, scanned using identical methods as part of an earlier study. Groups were matched for age, sex and symptom severity. RESULTS: Bilateral decreases in rCBF were observed in anteromedial regions of the medial frontal cortex and the cingulate cortex (Brodmann's areas (BA) 9 and 32) in the depressed PD group, compared with those with PD alone and compared with normal controls. This regional disturbance overlapped that observed in patients with primary depression. CONCLUSIONS: The findings indicate that the medial prefrontal cortex is a common area of neural dysfunction in the manifestation of both primary depression and depression in PD. PMID- 7994501 TI - The clinical diagnosis and misdiagnosis of senile dementia of Lewy body type (SDLT). AB - BACKGROUND: Current clinical classifications do not contain specific diagnostic categories for patients with senile dementia of the Lewy body type (SDLT), recently proposed as the second commonest neuropathological cause of dementia in the elderly. This study determines how existing clinical diagnosis systems label SDLT patients and suggests how such patients may be identified. METHOD: A range of clinical diagnostic criteria for dementia were applied to case notes of autopsy-confirmed SDLT (n = 20), dementia of Alzheimer type (DAT; n = 21) and multi-infarct dementia (MID; n = 9) patients who had received psychogeriatric assessment. The predictive validity of each set of clinical criteria was calculated against the external criterion of neuropathological diagnosis. RESULTS: Many SDLT patients erroneously met criteria for MID (35% with Hachinski scores > or = 7) or for DAT (15% by NINCDS 'probable AD', 35% by DSM-III-R DAT and 50% by NINCDS 'possible AD'). Up to 85% of SDLT cases could be correctly identified using recently published specific criteria. CONCLUSIONS: SDLT usually has a discernible clinical syndrome and existing clinical classifications may need revision to diagnose correctly such patients. PMID- 7994503 TI - The Nithsdale Schizophrenia Surveys. XII. 'Neurodevelopmental' Schizophrenia: a search for clinical correlates and putative aetiological factors. AB - BACKGROUND: The aim was to examine in a population of schizophrenic patients the clinical correlates of 'neurodevelopmental' schizophrenia and their relationship to putative aetiological factors. METHOD: Premorbid social adjustment, premorbid schizoid and schizotypal personality traits, and the obstetric history of 40 schizophrenic patients and their 102 sibs were assessed through interviews with their mothers. Patients' premorbid level of intelligence was assessed by the National Adult Reading Test and current symptoms by the Positive and Negative Syndrome Scale and the Subjective Deficit Syndrome Scale. RESULTS: Patients had more schizoid and schizotypal traits than their sibs. They showed a deterioration in social adjustment between childhood and adolescence; sibs' social adjustment improved. There were statistically significant associations between current negative schizophrenic symptoms, premorbid deterioration in social adjustment, and schizoid and schizotypal personality traits, and between an early age of onset of illness and the same premorbid assessments. There was no evidence that patients with a family history of severe mental illness leading to hospitalisation, or a history of definite obstetric complications, had poorer premorbid functioning or more severe current symptoms. CONCLUSIONS: We have confirmed clinical correlates of 'neurodevelopmental' schizophrenia but found no association between these and obstetric complications or a family history of severe mental disorder. PMID- 7994504 TI - The Nithsdale Schizophrenia Surveys. XIII. Parental rearing patterns, current symptomatology and relatives' expressed emotion. AB - BACKGROUND: A population of adult schizophrenic patients was assessed to discover how the patients viewed their childhood, whether their view differed from non schizophrenic adults, and to determine any association between parental rearing practices as perceived by the patient, childhood personality as perceived by the mother, and current symptoms. Type and level of expressed emotion shown by parents towards patients was also examined. METHOD: Parental attitudes, as perceived by 50 schizophrenic patients, were assessed by the EMBU scale. Patients' premorbid personality and social adjustment were assessed through interviews with patients' mothers by the Scale for the Assessment of Premorbid Schizoid and Schizotypal Traits and the Premorbid Social Adjustment Scale. Current symptoms were assessed by the Positive and Negative Syndrome Scale and Subjective Deficit Syndrome Scale. RESULTS: Patients saw little difference between fathers' and mothers' attitudes. There was a positive correlation between parental rejection and overprotection, and a negative correlation between rejection and warmth. There were no significant correlations between parental rearing attitudes and patients' childhood personality; there was a significant correlation between parental attitudes and current symptoms. Rejection and overprotection were associated with more severe, warmth with less severe symptoms, especially so for positive schizophrenic symptoms and general psychopathology. Although there was no association between the general level of expressed emotion shown by the parent towards the adult patient, and patients' perceived parental rearing attitudes, parents with high expressed emotion on the basis of hostility had higher rejection scores on the parental rearing attitudes scale. CONCLUSIONS: Schizophrenic patients saw their parents as showing much less warmth, and the severity of currents symptoms was associated with perceived parental rearing attitudes. The hostility component of high expressed emotion may be a parental trait which exists before the illness begins. PMID- 7994506 TI - Low birth weight and schizophrenia. AB - BACKGROUND: Low birth weight has been postulated to be a risk factor for schizophrenia. METHOD: Obstetric history, premorbid adjustment, and cognitive function during admission were assessed in 167 patients with DSM-III schizophrenia or affective psychosis. RESULTS: A birth weight of less than 2500 g was significantly more common in patients with schizophrenia than in those with affective psychosis. Schizophrenic patients as a group had significantly lower mean birth weight, a finding which was particularly marked after controlling for sociodemographic confounders. In schizophrenic men, lower birth weight was highly significantly correlated with poorer premorbid social and cognitive ability, and with impairment of adult cognitive function. CONCLUSIONS: Neurodevelopmental impairment may cause poor foetal growth, and schizophrenia in adult life. PMID- 7994505 TI - The relationship of schizophrenic births to 16 infectious diseases. AB - BACKGROUND: Recently, several investigators have reported an association between influenza epidemics and increased birth rates of 'preschizophrenic' individuals some four to six months later. Here we examine whether maternal exposure to other infectious diseases can also predispose the foetus to later schizophrenia. METHOD: Two independent sets of dates of birth of first admission schizophrenic patients, born between 1938 and 1965 in England and Wales, were obtained from the Mental Health Enquiry in England and Wales. Data on the number of deaths per month from 16 infectious diseases between 1937 and 1965 in England and Wales were also collected. We used a Poisson regression model to examine the relationship between deaths from infectious diseases and schizophrenic births. RESULTS: In the two separate data sets, increased national deaths from bronchopneumonia preceded, by three and five months respectively, increased numbers of schizophrenic births. We did not find any other significant associations between schizophrenic births and any of the other 15 infectious diseases. CONCLUSIONS: The association between deaths from bronchopneumonia and increased schizophrenic births some months later may be a reflection of the fact that bronchopneumonia deaths increase markedly during influenza epidemics. PMID- 7994507 TI - Lifetime comorbidity of panic attacks and major depression in a population-based study. Symptom profiles. AB - BACKGROUND: The co-occurrence of panic disorder and major depression in the same individual is common. A question to be answered is whether the comorbid disorder is a distinct one or may resemble one or other disorder. In this paper we examine whether the comorbid disorder is a distinct condition. METHOD: We examined the symptom profiles and rates of comorbidity of panic attacks and DIS/DSM-III major depressive disorder in a population-based sample from four sites of the National Institute of Mental Health (NIMH) Epidemiologic Catchment Area Program (n = 12,668). RESULTS: The co-occurrence of panic attacks and major depression over the lifetime was 11 times higher than expected by chance (OR = 11.4, 95% CI 9.5 to 13.6). Subjects with both panic and depression had worse symptoms than those who had only one disorder. However, the pattern of symptoms was remarkably similar, after overall severity was taken into account. Depressive symptoms associated with more severe forms of depression (e.g. guilt, suicidal thoughts or attempts, and motor disturbance) were more frequent in the comorbid group. CONCLUSIONS: These findings may indicate a worse severity when the two disorders occur in the same individual. PMID- 7994508 TI - Clonidine is not a useful adjunct to methadone gradual detoxification in opioid addiction. AB - BACKGROUND: The role of clonidine in the management of opioid-dependent individuals undergoing gradual detoxification. METHOD: A double-blind placebo controlled trial was conducted on 86 voluntary in-patients (59 male, 27 female) aged 18-47 years, at a specialist drug-dependence treatment unit. Patients entered the trial when on 40 mg of methadone daily or less, and were randomised to receive incremental doses of clonidine (increasing from 0.2 mg daily to 1.2 mg daily) during a 14-day period of gradual methadone detoxification and for four weeks thereafter. Blood pressure was monitored and severity of opioid abstinence was assessed by questionnaire and by clinical examination. RESULT: Half the subjects were withdrawn or defaulted from the trial by the end of two weeks, those receiving clonidine earlier than those receiving dummy medication (9 of the former and only one of the latter because of systemic hypotension). Similar proportions of subjects completed detoxification in the two groups. In those who completed detoxification, clonidine did not significantly reduce either the symptoms or objective signs of opioid withdrawal. CONCLUSIONS: These findings suggest that clonidine has no place as an adjunct to a programme of gradual opioid detoxification. PMID- 7994509 TI - Seasonal and weather factors in parasuicide. AB - BACKGROUND: Seasonal variation in suicide and parasuicide has previously been reported. Few investigations have examined whether meteorological factors could influence suicidal behaviour, and the inconclusive results produced may be due to a variety of methodological problems. The present study overcomes some previous difficulties and tested whether parasuicide admission rate is related to weather variables. METHOD: Over 12,000 admissions for parasuicide were analysed by month, season, and in relation to meteorological data, which were measured close to the admitting hospital. RESULTS: Marked seasonal (P < 0.001) and monthly (P < 0.001) variations in mean daily parasuicide numbers were seen in women but not men. Small but highly significant correlations were demonstrated between parasuicide rate and weather parameters (P < 0.01), which were more marked in women (P < 0.01). These effects were additional to the monthly variation (P < 0.05). CONCLUSIONS: Weather has a small influence on parasuicide. Gender differences in body temperature regulation might account for the sex difference seen. PMID- 7994510 TI - Oculogyric spasm in Asian psychiatric in-patients on maintenance medication. AB - BACKGROUND: The objective was to investigate the occurrence and characteristics of oculogyric spasm (OGS) in an Asian country. METHOD: All 2035 Asian (88% Chinese, 7% Malays and 5% Indonesians) psychiatric in-patients in the state psychiatric hospital in Singapore were surveyed for occurrence of oculogyric spasm (OGS) over a two-month period. RESULTS: Thirty-four patients (1.7%) developed OGS (53% male and 47% female). All the 34 patients had been on maintenance antipsychotic drugs for more than five months. Eighteen patients had recurrent attacks. The mean chlorpromazine equivalent daily dose for those patients with recurrent OGS was 511 mg. This was significantly higher (P < 0.05) than the 277 mg daily dose received by those without recurrent OGS. Most (68%) of the attacks occurred between 1400-2000 h suggesting that OGS may have a diurnal variation. CONCLUSIONS: OGS presenting as tardive dystonia may be due to a relative increase in cholinergic activity. PMID- 7994511 TI - Neuroleptic medication for dystonia. Reciprocal relationship between effects on motor function and mood. AB - BACKGROUND: The presence of dysphoric symptoms associated with neuroleptic medication is commonly reported. METHOD: Neuroleptic treatment of a segmental dystonia resulted in a disabling depressive illness, which when treated with antidepressants led to the return of the involuntary movements. RESULTS: The use of several different antidepressants and neuroleptics confirmed the association between drugs and symptoms. Genetic studies excluded "poor metaboliser status" as a reason for the patient's sensitivity to these drugs. CONCLUSIONS: The case illustrates a delicate imbalance between dose of neuroleptic medication and depressive symptoms. We should be aware of the possibility of mood changes in patients treated with neuroleptics for a variety of conditions. PMID- 7994512 TI - Exorcism-resistant ghost possession treated with clopenthixol. AB - BACKGROUND: An Indian man now in Britain explained his criminal behaviour as episodic ghost possession. Traditional exorcisms failed to help. METHOD: A 'Western' diagnosis of dissociative state or paranoid schizophrenia was made. Treatment commenced using trifluoperazine and clopenthixol. RESULTS: The patient underwent remission during neuroleptic treatment, despite previous evidence of genuine possession. CONCLUSIONS: Many cultures give rise to apparently genuine cases of ghost possession. Neuroleptics may relieve symptoms of exorcism resistant possession. PMID- 7994513 TI - Postal self-exposure treatment of recurrent nightmares. AB - BACKGROUND: Case reports suggest that recurrent nightmares are alleviated by behavioural treatment. We have administered such treatment to a client by post. METHOD: The frequency of nightmares was recorded by the client before and during treatment, and at one and six months follow-up. Nightmare problem and target scales, and treatment expectation were recorded at the end of each period. Treatment was by rehearsal relief, self-administered using written instructions. RESULTS: A reduction in nightmare frequency from 5.5 per week in the baseline period to an average of one per week resulted after treatment. CONCLUSIONS: The client's chronic nightmares were lastingly relieved after self-administered exposure treatment. A controlled trial is underway. PMID- 7994514 TI - Diversity of psychopathology associated with use of 3,4 methylenedioxymethamphetamine ('Ecstasy') AB - BACKGROUND: 3,4-methylenedioxymethamphetamine (MDMA or 'Ecstasy') has become one of the most widely used illicit substances in the UK. Little is known of the psychiatric morbidity which may be associated with its use. We have examined this association by collecting a series of psychiatric cases in which MDMA use was a prominent feature. METHOD: Patients presenting between 1990 and 1992 with psychiatric symptoms which developed in the context of MDMA use (n = 13) were interviewed, and their psychiatric, medical and drug history, sociodemographic background and mental state were examined in detail. The psychopathology of cases with psychosis (n = 8) was assessed with the Present State Examination and compared with that of substance-naive psychotic controls (n = 40). RESULTS: Eight patients presented with psychotic syndromes, two experienced visual illusions, hallucinations and palinopsia, one had panic attacks, one suffered from depression, and one described chronic depersonalisation and derealisation. The psychopathology of the patients with psychoses was very similar to that of controls. CONCLUSIONS: Use of MDMA may be associated with a broader spectrum of psychiatric morbidity than heretofore suspected. Cases with psychosis may be clinically similar to psychotic patients with no history of substance use. PMID- 7994515 TI - The prevalence of autistic disorder among children with a learning disability. AB - BACKGROUND: It has been suggested recently that the prevalence of autistic disorder may be rising. No prevalence study specifically among learning disabled children exists and so this study was prompted. METHOD: 767 children with a learning disability who attended 16 different special schools in the Grampian region of north-east Scotland were studied for a diagnosis of autistic disorder according to the DSM-III-R criteria. The study was conducted in three stages. In the first screening stage, a questionnaire was completed for each child by their teachers. In the second stage, teachers completed another questionnaire based on DSM-III-R criteria for autistic disorder. A final diagnosis was made on the basis of examination and information gathered from the questionnaires. RESULTS: Questionnaires were completed for 634 (82.7%) children. 14.3% of children with a learning disability fulfilled the diagnostic criteria for autistic disorder. There was a male:female ratio of 3:1. This gave a 9 per 10,000 minimum prevalence of autistic disorder among all school-age children in the Grampian region. There was a higher prevalence of autistic disorder in the cities compared with rural areas. The prevalence did not change with age but increased with decreasing IQ. CONCLUSION: The results of the study support the view that there may be an increasing prevalence of reported cases of autistic disorder. PMID- 7994516 TI - Clinical features and diagnostic criteria of depression in Down's syndrome. AB - BACKGROUND: Depression occurs commonly in people with Down's syndrome, although there is little published about this association. This study explores the limitations of Diagnostic Criteria for Research, based on ICD-10 (DCR) and DSM III-R depressive criteria. METHOD: Case not examination identified 42 adults with Down's syndrome who have sustained 56 depressive episodes. The clinical features are reported. RESULTS: All episodes were diagnosed as depression. DSM-III-R criteria for major depressive episode were met by 50% of the episodes. DCR for depressive episode of at least mild severity were fulfilled by 68%. CONCLUSIONS: These criteria were unduly restrictive for this group. Commonly occurring symptoms are not included in the criteria, while certain criteria items never occurred. Criteria should be modified to facilitate future research. PMID- 7994517 TI - Cerebral hemiatrophy and schizophrenia. AB - BACKGROUND: Neuroimaging of a treatment-resistant patient with schizophrenia revealed the existence of cerebral hemiatrophy. The association of schizophrenia with cerebral hemiatrophy has not previously been reported. RESULTS: Neuroimaging with X-ray computerised tomography showed marked reduction in the volume of the left cerebral hemisphere with secondary enlargement of the left lateral fissure and cortical sulci. High resolution cranial single-photon emission computerised tomography showed a functional deficit of the regional cerebral blood flow in the left lateral parietal and left temporal lobes. CONCLUSIONS: Cerebral hemiatrophy may belong to the lengthening list of neurodevelopmental cerebral anomalies associated with schizophrenia. PMID- 7994518 TI - Arabic expression of emotion. PMID- 7994519 TI - Clozapine-induced neutropenia, or not. PMID- 7994520 TI - Obsessive-compulsive symptoms and clozapine. PMID- 7994521 TI - Strength of the genetic effect in schizophrenia. PMID- 7994522 TI - Lithium prophylaxis in recurrent affective illness. PMID- 7994523 TI - Dyskinesia and withdrawal from alcohol. PMID- 7994524 TI - Cannabis consumption and schizophrenia. PMID- 7994525 TI - Cocaine, psychiatric admissions, and HIV. PMID- 7994526 TI - Cocaine, psychiatric admissions, and HIV. PMID- 7994527 TI - Delusion of inanimate doubles. PMID- 7994528 TI - Unipolar mania in non-Western cultures. PMID- 7994529 TI - Solvent abuse in psychiatric settings. PMID- 7994530 TI - Prevalence of Huntington's disease in the Oxford region. PMID- 7994531 TI - The status of asylum medical officers. 1894. PMID- 7994532 TI - Transsexualism and gender reassignment. AB - Gender reassignment for carefully assessed transsexual patients is now an established and accepted practice in many parts of the world. In other areas customary attitudes to those with sexual differences prevents consideration. A large number of autobiographies by reassigned patients have been published and all throw light on the experience of the writers. The one which may be recommended is that by Morris (1974). For the interested lay-person enquiring about the nature of transsexualism the brief book by Hodgkinson (1987) may be recommended. PMID- 7994533 TI - [The development of a test system for determining antibodies to Bacteroides melaninogenicus using solid-phase immunoenzyme analysis]. AB - A test system for enzyme immunoassay of antibodies to Bacteroides melaninogenicus has been developed. The authors describe a method for the preparation of the protein and polysaccharide antigens with the use of ultrasonic, lysozyme, and beta-naphthol treatment. A total of 105 blood serum samples, 46 samples of gingival blood and gingival fluid from patients with maxillofacial phlegmons and periodontitis were examined, making use of the 1 +/- 3 omega index (from the values in healthy donors). The results evidence statistically significant difference in antibody levels of patients from whom B. melaninogenicus were isolated and of those with the negative results of bacteriologic analysis. The titers of antibodies to B. melaninogenicus in the blood and gingival fluid of patients with periodontitis were in good correlation. PMID- 7994534 TI - [The hazards of methodological mistakes in determining human protection from diphtheria and tetanus]. PMID- 7994535 TI - [The choice of the method for determining the potential pathogenicity of shigellae]. AB - The biological characteristics of 196 Shigella strains, isolated in regions with different levels of the geomagnetic field tension, were under study. Strains able to adsorb Congo red, characterized by antilysozyme activity, hydrophobic, resistant to gentamycin, monomycin, kanamycin, rifampicin were more frequently isolated in the regions with a higher tension of the field, this being confirmed by a stable correlation. The ability of Shigellae to fix Congo red correlated with the before signs and with colicinogenicity, therefore this test may be recommended for the assessment of Shigella virulence. PMID- 7994536 TI - [The isolation of Helicobacter pylori from the gastric juice]. AB - Gastric contents was examined in 49 patients with duodenal bulb ulcers. Helicobacter pylori were isolated in 83.7% of cases. H. pylori density was found to be 10(3)-10(5) microbial cells per ml. Bacterioscopic studies with gram staining helped detect H. pylori in 79.6% of cases, cultural method revealed the bacteria in 63.3%, and urease test in 4.1% of cases. Poor efficacy of urease test is explained by its poor sensitivity (10(6) microbial cells per ml or higher). The authors analyze the frequency of H. pylori isolation in relation to the month of the examination and gastric contents coloring. PMID- 7994537 TI - [A method of preparing specimens for the electron microscopic study of bacterial fimbrial structures]. AB - A method for making bacterial preparations for studies of fimbrial structures by electron microscopy has been developed, making use of impressions of 'young' colonies in agar microscopy. The suggested method involves three steps: cultivation of the examined bacteria in lamellar media till they attain the 'young' age; agar microscopy of the grown culture and making of impressions from the selected sites; contrasting of the objects and drying of the preparations. The new method is simple, economic, highly reliable and yields good results. It maximally rules out the factors conducive to rupture and injury of fimbria, observed in traditional method of making the preparations. PMID- 7994538 TI - [A means for determining the bactericidal activity of the tissues during the treatment of orthopedic patients by transosseous osteosynthesis methods]. AB - The author suggests a new method for the assessment of the bactericidal activity of local tissues in the treatment of bone fractures or after effects thereof by the transosseous osteosynthesis methods. Tissue components may induce the formation of large sites of delayed growth in standard Micrococcus lysodeikticus cultures. To assess the bactericidal activity of the tissues, a standard diagnostic disk with an antibiotic is placed onto such cultures, this permitting the expression of the tissue bactericidal activity in equivalents of the antibiotic antibacterial effect and determine the low, medium, and high levels of the tissue bactericidal activity with respect to the minimal therapeutic suppressing concentration of this antibiotic. The author suggests that the mechanism of a drastic elevation of the local tissue bactericidal activity in transosseous osteosynthesis is explained by an essential enhancement of local tissue metabolism. PMID- 7994539 TI - [The cytological possibilities for the early diagnosis of neuroleukemia]. AB - The authors present the results of analyses of 425 samples of the cerebrospinal fluid from 67 patients with acute leukemia and from 30 ones with chronic myeloleukemia, carried out by the sedimentation method. This method permits concentration of the cells on a small site of the slide, involving the minimal injury to the cells, and thus helps obtain the cellular picture of the liquor, available for morphologic analysis. Detection in the sedimentation preparations with normal parameters of liquor cytosis of the blast cells in patients with acute leukemia and of the entire spectrum of maturing granulocytes with blasts in chronic myeloleukemia patients permits the diagnosis of the preclinical stage of neuroleukemia and thus helps detect the patients, for whom all the measures, included in the neuroleukemia prevention program, are absolutely obligatory and whose cerebrospinal fluid cellular composition should be regularly checked up. PMID- 7994540 TI - [Immunochemical methods for the diagnosis of pseudotuberculosis (a review of the literature)]. PMID- 7994541 TI - [Cytometry and the degree of differentiation of squamous-cell lung cancer]. AB - Cytometric studies of samples from 65 patients (20 with well-differentiated carcinoma, 32 with moderately differentiated and 13 with poorly differentiated tumors), carried out with the Integral-2MT cytoanalyzer, have shown an inverse relationship between the size of the nuclei, nuclear-cytoplasmatic ratio, and the degree of pulmonary carcinoma differentiation. The results of the study will promote a more objective assessment of carcinoma cells and will improve the efficacy of cytologic diagnosis of squamous cell carcinoma of various differentiation degrees. PMID- 7994542 TI - [The organization of hematological monitoring for the population living in regions with strict radiation control]. AB - Presents an algorithm of hematologic check-ups of the population living in regions contaminated as a result of the Chernobyl power plant accident, comprising regular clinical, morphologic, cytochemical, biochemical, immunologic, karyologic studies. Hematologic monitoring will be conducive to an earlier detection of oncohematologic and other blood system diseases, to their prevention and effective therapy. PMID- 7994543 TI - [The assessment of the proliferative activity of bone marrow cells by flow cytofluorometry]. AB - The distribution of bone marrow cells by the stages of cellular cycle (G1/0, S, G2 + M) was studied in 56 hematologically normal subjects and in 30 anemic patients by flow cytofluorometry. In health the analyzed parameters were found rather stable, well reproducible, this permitting their use as reference values. In pernicious anemia the S-phase fraction of bone marrow cells was found increased; a lesser increase was observed in the counts of myelokaryocytes in the postsynthetic phase of the mitotic cycle; in iron deficiency anemia these parameters virtually did not differ from the reference values, whereas in autoimmune anemia the pool of proliferating cells was increased. The author discusses the problems of the pathogenesis of anemias and the diagnostic value of his results. PMID- 7994544 TI - [An improved method for isolating blood monocytes]. AB - The authors have improved the method for the gradient isolation of monocytes from human whole blood: an expensive reagent, percoll, is replaced by verograffin, an x-ray contrast agent. Monocytes were isolated by this method from the blood of 8 normal subjects. The isolated monocytes were identified and their population composition studied electronmicroscopically, cytochemically, and immunocytochemically. The monocyte population of healthy donors was found morphologically and cytochemically heterogeneous, consisting of 4 types of cells, forming on the monocytogram stable (in their per cent shares) classes. The improved method for monocyte isolation and the results of morphometric analysis may be used to assess the system of human mononuclear phagocytes in various diseases. PMID- 7994545 TI - [The use of the induced test of nitroblue tetrazolium reduction for the diagnosis of fungal bronchial asthma]. AB - The NBT reduction test was used to assess the neutrophilic activities in 49 patients with bronchial asthma. 12 healthy donors were examined for control. The NBT test values were lower in health than in asthma: 8.8 +/- +0.97 vs. 12.8 +/- 0.7%, respectively, p < 0.05. Addition of a specific fungal allergen resulted in a twofold increase of the count of formasan-positive cells. A lower, but still a significant increase of the count of active granulocytes was induced in the asthmatics by home dust allergen (17.7 +/- 0.91%). The results of induced NBT test and of the reaction of antigen-specific injury of the granulocytes were in excellent correlation (r = 0.65, p < 0.05). There was no correlation of this test data with those of indirect Shelley's test or skin tests. This fact indicates the contribution of both the immediate and delayed mechanisms to the pathogenesis of fungal bronchial asthma. PMID- 7994546 TI - [The use of the autocoagulation test for the detection of coagulopathies in rheumatoid arthritis]. AB - The parameters of plasma-platelet component of hemostasis were studied by autocoagulation test in 90 patients with rheumatoid arthritis of varying activity. To specify the role of blood platelets, their counts were estimated, as was their functional activity. Plasma coagulating activity was found elevated and anticoagulating activity reduced in disease of the first and second degrees of activity, particularly so in the second degree. In patients with the third activity degree these parameters are within the normal range. The platelets augment hypercoagulation signs and reduce plasma anticoagulation potential in disease of the third degree of activity most of all. This leads to augmentation of thrombophilia signs, thus creating favorable conditions for intravascular coagulation and formation of microthrombi, which may eventually result in aggravation of rheumatoid synovitis and development of visceritis. PMID- 7994548 TI - [The use of different albumin preparations as calibrators in determining the total protein in blood serum by the biuret method]. AB - The authors have investigated the possibility of using various albumin preparations as calibrators in measurements of human blood serum total protein by the biuret method. Analysis of Precinorm U and Precipath U reference sera has demonstrated that use of various albumin preparations as calibrators may result in significant deviations (as much as 27%) of the resultant values from the due ones. PMID- 7994547 TI - [The diagnostic significance of soluble fibrin monomer complexes in exacerbated chronic recurrent pancreatitis]. AB - The authors theoretically explain the elevation of blood plasma levels of soluble fibrin monomer complexes occurring in elevated trypsin concentrations in the blood. Examinations of 50 patients with chronic relapsing pancreatitis and of 20 donors demonstrated a marked correlation between the levels of immunoreactive trypsin and soluble fibrin-monomer complexes in the blood. The authors recommend measurements of blood soluble fibrin-monomer complexes for the diagnosis of exacerbations of chronic relapsing pancreatitis. PMID- 7994550 TI - [The determination of microalbuminuria by immunoenzyme analysis]. AB - The authors have defined the optimal conditions for inhibitory type enzyme immunoassay of microalbuminuria. The range of albumin detection is 30 to 250 micrograms/ml. The optimal time of antigen binding with antibody is 45 min, the lower threshold level of albumin detection 0.6 +/- 0.02 microgram/ml. Albumin concentration is unchanged after urine storage for 8 weeks at -20 degrees C or for 1 week at 4 degrees C. PMID- 7994549 TI - [Normal serum prealbumin and in pathology]. PMID- 7994551 TI - [The discriminant interval as a means for assessing the results of laboratory studies]. PMID- 7994552 TI - [Uric acid: its diagnostic significance and study methods (a review of the literature)]. PMID- 7994553 TI - [The prognosis of a protracted course of pseudotuberculosis in chronic opisthorchiasis]. AB - Forty-five pseudotuberculosis patients with concomitant chronic opisthorchiasis were examined at the peak of infection and in early convalescence, as were 30 patients with chronic opisthorchiasis and 30 normal subjects. The immunologic status of pseudotuberculosis patients coursing in the presence of chronic opisthorchiasis was found changed. Reduction of B lymphocyte counts by 1.7 times, of absolute theophyllin-resistant counts by 1.6 times, and of the relative theophyllin-resistant lymphocyte counts by 2 times and elevated levels of circulating immune complexes (by 3 times) and of IgE (by 3.5 times) vs. the norm in the early periods of the disease predict a protracted course of pseudotuberculosis in the presence of chronic opisthorchiasis. PMID- 7994554 TI - [The automatic analysis of the formed elements of the blood in a clinical diagnostic laboratory. The current and future outlook]. PMID- 7994555 TI - [Experience with the use of "dry" chemistry reagents iin Austria]. PMID- 7994556 TI - Inhibition of mitochondrial superoxide generation in rat alveolar macrophages by 12-O-tetradecanoylphorbol-13-acetate: potential role of protein kinase C. AB - We have observed that lucigenin-derived chemiluminescence (CL) measures superoxide anion (O2-) production from two major cellular compartments in rat alveolar macrophages (AMs): extracellular O2- produced by NADPH oxidase; and intracellular O2- produced by the reduction of molecular oxygen by the mitochondrial electron transport chain. Although the treatment of AMs with 30 ng/mL 12-O-tetradecanoyl phorbol-13-acetate (TPA) increases the production of O2- by NADPH oxidase, the net result of TPA addition monitors is a decrease in lucigenin-derived CL resulting from inhibition of mitochondrial-derived O2- production. Since protein kinase C (PKC) has been shown to be the cellular receptor through which TPA mediates its effects, it was postulated that activation of PKC inhibits mitochondrial-derived O2- production as measured by lucigenin-derived CL. Studies performed with 50 microM H-7 (a PKC inhibitor) support this hypothesis by blocking the inhibition of mitochondrial-derived CL by TPA, while HA-1004, a negative control for H-7, had no effect on the system. These results suggest that mitochondrial respiration may be modulated by the actions of PKC. Moreover, this observation suggests a novel mechanism whereby chemicals which activate PKC may affect cellular function through modulation of mitochondrial activity. PMID- 7994557 TI - Human carcinoma cell lines produce biologically active leukemia inhibitory factor (LIF). AB - We investigated the production of leukemia inhibitory factor (LIF) by human carcinoma cell lines. LIF mRNA was detected by Northern blot analysis in all 24 carcinoma cell lines of the lung, breast, stomach, colon, liver, gallbladder, pancreas and melanocytes. Seventeen of them (70.8%) secreted LIF in the culture supernatant (range: 40.4-3990.3 pg/ml, mean +/- SEM: 611.8 +/- 262.9 pg/ml). Biologic activity of LIF was confirmed in the culture supernatant of carcinoma cell lines by the MTT assay using M1 cells. The present results showed that human carcinoma cell lines are constitutively producing biologically active LIF. The possible biological significance of LIF produced by cancer cells is discussed. PMID- 7994558 TI - Cell membrane fluidity in K562 cells and its relation to receptor expression. AB - Cell membrane fluidity (CMF) and transferrin receptor (Tf-R) expression were investigated in K562 cells, a human chronic myelocytic leukemia cell line, treated by gamma-interferon (IFN-gamma). CMF was increased using spin-labeled electron spin resonance techniques, and Tf-R expression was measured by flow cytometric analysis with an EPICS-750 flow cytometer/cell sorter. Treatment of K562 cells in suspension culture with IFN-gamma for as long a time as 6 hr caused an increase in CMF, and then returned to the level of control cells at 12 hr. Conversely, by 24 hr after the beginning of treatment, the rigidity of CMF was increased. Thus, the changes of IFN-gamma-induced CMF was biphasic. While the early change of CMF is related to signal generation and transmission, the later change may reflect changes in lipid compositions and/or cytoskeletal complexes of the plasma cell membrane. A significant increase of Tf-R after 6 hr and 24 hr in number was obtained by treatment of K562 cells with IFN-gamma, but at 12 hr the number of Tf-R did not differ from the control. These results suggested that the early phase of upregulation of Tf-R induced by IFN-gamma was caused by increased CMF, and the late phase of upregulation of Tf-R was due to increased rigidity of CMF. In conclusion, the state of CMF associated with a certain receptor expression in cells is not rigid and can be modulated to some extent by exogenous influences. This may open possibilities of some adjuvant therapeutic measures in malignant diseases by increasing the antigenicity of tumor cells. PMID- 7994559 TI - Assessment of in vitro growth potential of hepatocytes expressing hepatocyte growth factor in an autocrine fashion. AB - We recently developed transgenic mice expressing hepatocyte growth factor (HGF) specific to hepatocytes. Hepatocytes of HGF transgenic mice showed a 2-fold increase of DNA labeling indices in vivo compared with those of wild type mice. To assess in vitro growth potential of hepatocytes from HGF transgenic mice, we studied the effects of epidermal growth factor (EGF), insulin or transforming growth factor beta (TGF beta) on DNA synthesis of hepatocytes derived from HGF transgenic or wild type mice, respectively. We found that DNA synthesis of hepatocytes from HGF transgenic mice was significantly enhanced, compared with that from wild type mice, respectively, and that its effect was additive with EGF or insulin. Further, growth-inhibitory effects of TGF beta on hepatocytes was greatly depressed in transgenic mice-derived hepatocytes, compared with that in wild type hepatocytes. These data suggest that the autocrine action of HGF is a potent stimulus for hepatocyte growth, and stress its importance as regulator of liver regeneration. PMID- 7994560 TI - Serum hepatocyte growth factor in acute hepatic failure in comparison with acute hepatitis. AB - Serum hepatocyte growth factor (HGF) levels in patients with acute hepatic failure has been reported to increase. However, possible mechanisms responsible for HGF elevation in this syndrome remains to be determined. To explore the possible mechanisms, we measured serum HGF in patients with acute hepatic failure and self-limited acute hepatitis, using an immunoradiometric assay. Serum HGF levels in acute hepatic failure were 36-fold higher compared with those in acute hepatitis. Serum HGF values in acute hepatitis were significantly correlated with serum bilirubin and gamma-GTP levels, whereas those in acute hepatic failure were not. These clinical findings suggest that serum HGF levels in acute hepatic failure may be regulated by different mechanisms from those in self-limited acute hepatitis. PMID- 7994561 TI - Alterations of membrane fluidity in K562 cells exposed to the anticancer drug adriamycin. AB - The incubation of K562 cells with adriamycin resulted in a decrease in cell membrane fluidity as measured by electron spin resonance using the paramagnetic probe 5-doxylstearic acid. Coincidently, the antiproliferative effect of adriamycin was progressively inhibited as the concentration of adriamycin was increased. The results indicate that adriamycin induces changes in the plasma membrane of K562 cells after exposure to a low level of this agent. PMID- 7994562 TI - Pertussis toxin pretreatment alters agonist binding to beta-adrenoceptors in rabbit ventricular myocardium. AB - The influence of pretreatment with pertussis toxin (PTX) on characteristics of beta-adrenoceptor bindings was examined in myocardial ventricular membranes prepared from rabbits which received an intravenous injection of PTX (10 micrograms/kg) or its vehicle. The density and affinity of beta-adrenoceptors assessed by (-)-[125I]iodocyanopindolol were not significantly altered by PTX pretreatment. However, a fraction of agonist binding sites with high affinity significantly increased in PTX-pretreated myocardial membranes. In the presence of 100 microM 5'-guanylyl imidodiphosphate, all agonist binding sites were converted to low-affinity sites in both control and PTX-pretreated membranes. The results suggest that Gi might regulate negatively coupling of beta-adrenoceptors to Gs. PMID- 7994563 TI - Erythromycin inhibits cholinergic neuro-effector transmission in canine airway smooth muscle. AB - To elucidate whether macrolide antibiotics affect cholinergic neuro-effector transmission in the airway, we studied canine isolated bronchial segments under isometric conditions in vitro. Addition of erythromycin (3 x 10(-4) M) attenuated the contractile responses to electrical field stimulation (EFS), so that the stimulus frequency required to produce a half-maximal contraction (ES50) increased from 1.3 +/- 0.3 to 5.1 +/- 0.5 Hz (p < 0.001). This effect was concentration-dependent and not influenced by propranolol, indomethacin, ouabain or mechanical removal of the epithelium. In contrast, contractile responses to acetylcholine were not altered by erythromycin. These results suggest that erythromycin may inhibit neuro-effector transmission in the airway cholinergic motor pathway, probably involving the reduction of exocytotic release of acetylcholine from the nerve terminals. PMID- 7994564 TI - Effects of novel antiarrhythmic agents, BRB-I-28 and its derivatives, on the heart mitochondrial respiratory chain and sarcoplasmic reticulum Ca(2+)-ATPase. AB - The effects of BRB-I-28 and its derivatives (GLG-V-13, SAZ-VII-22 and SAZ-VII 23), a novel group of antiarrhythmic agents, were investigated on the rat heart mitochondrial respiratory chain. The results indicate that BRB-I-28 and its derivatives have concentration-dependent inhibitory effects on NADH oxidase and NADH-CoQ reductase (complex I), but they have no significant effects on succinate oxidase, succinate dehydrogenase (complex II), CoQ-cytochrome c reductase (complex III), cytochrome c oxidase (complex IV), and NADH-K3Fe(CN)6 reductase. The site of inhibition of BRB-I-28 and its derivatives on the respiratory chain was localized between flavoprotein n (FPn) and CoQ, which is similar to the effect of rotenone and several other antiarrhythmic drugs such as amiodarone, propranolol, etc. BRB-I-28 and its derivatives also have significant inhibitory effects on mitochondrial ATPase activity as reported for other antiarrhythmic drugs such as amiodarone, propranolol, quinidine, and lidocaine. However, BRB-I 28 and its derivatives have no direct effects on sarcoplasmic reticulum Ca(2+) ATPase activity. The inhibitory effects of BRB-I-28 and its derivatives on mitochondrial oxidative phosphorylation may result in the depletion of ATP. This effect, in combination with their effects on Na+,K(+)-ATPase, could possibly produce an increase in Ca2+ concentration in cytosol. This may be another mechanism by which these DHBCN derivatives produce an increase in systemic arterial blood pressure and contractile force of isolated cardiac muscle. On the other hand, inhibition on mitochondrial respiration may account for some of the potential toxic effects of these diheterabicyclo[3.3.1]nonane derivatives. PMID- 7994565 TI - Azelastine inhibits acute allergic dyspnea in a conscious guinea pig asthma model. AB - A simple, noninvasive, bias-flow ventilated wholebody plethysmographic technique and noninvasive pulmonary analyzer (Buxco dyspnea monitor) were used to quantitate allergic dyspnea in chronically sensitized freely moving guinea pigs. In this study, the effect of azelastine on aeroallergen-induced dyspnea in allergic guinea pigs was investigated. Aeroallergen challenge produced severe dyspnea which was characterized by a 390% increase in the amplitude of pseudo flow signal, a 93% increase in box pressure (delta P) and a 68% decline in relaxation time; these changes signify a tremendous increase in the effort of breathing. The oral administration of azelastine (1 mg/kg) two hours before aeroallergen provocation significantly inhibited allergic dyspnea in this acute allergic asthma model. This technique permits quantitative measurement of the severity of the airway allergic responses in freely moving guinea pigs. PMID- 7994566 TI - Removal of copper from the liver of Long-Evans Cinnamon (LEC) rats by tetrathiomolybdate (TTM) injection: the main excretion route is via blood, not bile. AB - Tetrathiomolybdate (TTM) was injected at a dose of 10 mg/kg bw daily for eight consecutive days into Long-Evans Cinnamon (LEC) rats, which inherently abnormally deposit Cu (260 micrograms/g) in the liver. The hepatic Cu (100 micrograms/g) and metallothionein (MT) bound Cu (from 2,600 to 540 micrograms/g protein) concentrations were decreased greatly by the injection. On the other hand, the renal Cu concentration increased significantly, but the brain Cu concentration only very slightly. The reduction of the hepatic Cu concentration was accompanied by reductions of Zn and Fe concentrations in the liver, kidney and brain. The TTM compound slightly stimulated excretion (about 3-fold) of Cu into the bile, but greatly (about 40-fold) into the blood. In rats not treated with TTM, most biliary (100%) and serum (78%) Cu was recovered in the trichloroacetic acid (TCA) soluble fraction. On the other hand, in rats treated with TTM, bile and serum Cu were recovered overwhelmingly in the TCA insoluble fraction, probably in the form of a Cu-TTM-albumin complex. Our results suggest that although there is an inherent failure in the intrinsic secretory process of Cu from the liver in LEC rats, the TTM compound can remove Cu from Cu-MT, resulting in a decrease of hepatic Cu. PMID- 7994567 TI - Effect of terbium on protease activity in pancreas of mice. AB - The effect of terbium (Tb) on the protease activity in pancreas of mice was studied. Administration of Tb at doses of 20 and 200 mumol/kg increased the activities of trypsin and carboxypeptidase A, but did not affect the activities of chymotrypsin and carboxypeptidase B. High Tb concentrations were found in the liver and spleen compared to the kidney and pancreas. Increases in Ca concentrations in the pancreas, kidney, and spleen after Tb administration were observed. The pancreatic slice experiments showed the increase in trypsin activity after Tb treatment and increases in trypsin and carboxypeptidase A after Ca treatment. Tb inhibited strongly the activities of authentic chymotrypsin and carboxypeptidase A. These results suggest that the increase in trypsin activity in the pancreas after Tb administration results from the activation of trypsinogen by Tb and Ca ions and that the increase in carboxypeptidase A activity is due to the activation of procarboxypeptidase A by trypsin and Ca ion, which increased after Tb administration. PMID- 7994568 TI - Hyponatremia and neuroleptic-induced obesity in rats. AB - The weight gain and hyperphagia induced by chronic administration of sulpiride in female rats were not prevented by the concomitant administration of an extra source of sodium. In addition, serum sodium levels were not affected, but potassium levels were significantly reduced by sulpiride administered for 1 week. These results suggest that sulpiride-induced obesity in rats is not related to sodium imbalance. The mechanism for the decrease in serum potassium levels and its relation with sulpiride-induced weight gain warrant further investigation. PMID- 7994569 TI - Structure-based drug design of antirhinoviral compounds. AB - Improved knowledge of rhinovirus structures makes it possible to identify three promising targets for broad-spectrum antirhinoviral drugs. PMID- 7994570 TI - Solution structure of a peptide fragment of human alpha-lactalbumin in trifluoroethanol: a model for local structure in the molten globule. AB - BACKGROUND: At low pH, human alpha-lactalbumin forms a partly folded molten globule state that contains a non-native clustering of the side chains of Tyr103, Trp104 and His107. In order to understand the conformation of this region of the protein in the molten globule state, we investigated the structure of a peptide corresponding to residues 101-110 of human alpha-lactalbumin in trifluoroethanol. RESULTS: We determined the structure of the 101-110 peptide from an NMR data set of 145 nuclear Overhauser effects and nine 3JHN alpha coupling constants, using an ensemble calculation approach to take into account the possibilities of conformational averaging of the data. The backbone of residues 3-10 in the peptide adopts a series of turns, that involving residues 5-8 being the best defined, while the side chains of residues 1, 3, 4, 5, 6 and 7 form a hydrophobic cluster. CONCLUSIONS: The peptide conformation differs from that previously determined for residues 101-110 in crystal structures of native alpha-lactalbumin determined at both high and low pH, particularly in the relative orientations of the side chains. The series of turns seen in the peptide could, however, be related to the alpha-helical structure seen for residues 104-111 in crystals at high pH, and may be important in the molten globule state for bringing the peptide chain into a compact conformation where favourable interactions between the side chains can occur. PMID- 7994571 TI - Salt bridge relay triggers defective LDL receptor binding by a mutant apolipoprotein. AB - BACKGROUND: Apolipoprotein-E (apo-E), a 34kDa blood plasma protein, plays a key role in directing cholesterol transport via its interaction with the low density lipoprotein (LDL) receptor. The amino-terminal domain of apo-E forms an unusually elongated four-helix bundle arranged such that key basic residues involved in LDL receptor binding form a cluster at the end of one of the helices. A common apo-E variant, apo-E2, corresponding to the single-site substitution Arg158-->Cys, displays minimal LDL receptor binding and is associated with significant changes in plasma cholesterol levels and increased risk of coronary heart disease. Surprisingly, the site of mutation in this variant is physically well removed (> 12A) from the cluster of LDL receptor binding residues. RESULTS: We now report the refined crystal structure of the amino-terminal domain of apo-E2, at a nominal resolution of 3.0A. This structure reveals significant conformational changes relative to the wild-type protein that may account for reduced LDL receptor binding. Removal of the Arg158 side chain directly disrupts a pair of salt bridges, causing a compensatory reorganization of salt bridge partners that dramatically alters the charge surface presented by apo-E to its receptor. CONCLUSIONS: It is proposed that the observed reorganization of surface salt bridges is responsible for the decreased receptor binding by apo-E2. This reorganization, essentially functioning as a mutationally induced electrostatic switch to turn off receptor binding, represents a novel mechanism for the propagation of conformational changes over significant distances. PMID- 7994572 TI - Crystal structures of influenza virus hemagglutinin in complex with high-affinity receptor analogs. AB - BACKGROUND: The first step in influenza A virus infection involves attachment to cells through binding of viral hemagglutinin to cell-surface receptors containing alpha-5-N-acetylneuraminic acid (sialic acid). The structures of soluble hemagglutinin in isolation and in complex with several low-affinity receptor analogs have been solved previously to approximately 3A resolution. To design effective, and possibly therapeutic, inhibitors of viral attachment we have determined the structure of hemagglutinin in complex with four high-affinity (10 fold to 100-fold higher affinity) sialic acid analogs at higher resolution. RESULTS: In each crystal structure the sialic acid moiety is equivalently positioned in the receptor binding site but the substituent groups that differentiate the high-affinity analogs from each other interact with hydrophobic patches and polar residues adjacent to the binding site. Re-examination of the receptor binding site at 2.15A resolution reveals several hydrophilic pockets and an apolar channel that adjoin the receptor binding site. CONCLUSIONS: The interactions observed in the structures of soluble hemagglutinin in complex with receptor analogs suggest explanations for the observed affinities of the analogs, designs for potential sialic acid analogs with even higher affinities, and ideas both for inhibiting membrane fusion and for circumventing evasion of inhibition by antigenic variation. PMID- 7994573 TI - The structure of a complex between the NC10 antibody and influenza virus neuraminidase and comparison with the overlapping binding site of the NC41 antibody. AB - BACKGROUND: While it is well known that different antibodies can be produced against a particular antigen, and even against a particular site on an antigen, up until now there have been no structural studies of cross-reacting antibodies of this type. One antibody-antigen complex whose structure is known is that of the influenza virus antigen, neuraminidase, in complex with the NC41 antibody. Another anti-neuraminidase antibody, NC10, binds to an overlapping site on the antigen. The structure of the complex formed by this antibody with neuraminidase is described here and compared with the NC41-containing complex. RESULTS: The crystal structure of the NC10 Fab-neuraminidase complex has been refined to a nominal resolution of 2.5A. Approximately 80% of the binding site of the NC10 antibody on neuraminidase overlaps with that of the NC41 antibody. The epitope residues of neuraminidase are often engaged in quite different interactions with the two antibodies. Although the NC10 and NC41 antibodies have identical amino acid sequences within the first complementarity determining region of their heavy chains, this is not the basis of the cross-reaction. CONCLUSIONS: The capacity of two different proteins to bind to the same target structure on a third protein need not be based on the existence of identical or homologous amino acid sequences within those proteins. As we have demonstrated, amino acid residues on the common target structure may be in quite different chemical environments, and may also adopt different conformations within two protein-protein complexes. PMID- 7994574 TI - The structure of an asymmetric dimer relevant to the mode of action of the glycopeptide antibiotics. AB - BACKGROUND: Glycopeptide antibiotics of the vancomycin group are of crucial clinical importance in the treatment of methicillin resistant Staphylococcus aureus (MRSA)--the often lethal 'super-bug'--characterized by its resistance to a wide range of antibiotics in common use. The antibiotics exert their physiological action by blocking cell wall synthesis through recognition of nascent cell wall mucopeptides terminating in the sequence -D-Ala-D-Ala. Evidence suggests that the antibiotics are able to enhance their biological activity by the formation of homodimers, and this is supported by the observation that dimerization and peptide binding in vitro are cooperative phenomena. The basis of this enhancement is not understood at the molecular level. RESULTS: The first detailed structure of a dimeric glycopeptide antibiotic, that of eremomycin, is presented based upon solution NMR data. The overall structure of the dimer complex is asymmetric. The source of this asymmetry--a parallel alignment and mutual interaction of the disaccharides--appears to promote dimerization through specific sugar-sugar recognition. CONCLUSIONS: A molecular basis for the observed cooperativity of cell wall peptide binding by eremomycin is evident from these studies of the dimer. The carboxylate anion of the cell wall component, which is crucial to binding, forms an amide-mediated ion-pair interaction to the alkylammonium ion of the ring 6 sugar in the other half of the dimer making the structure and positioning of this sugar important in mediating cooperativity. PMID- 7994575 TI - Crystal structure of the extracellular region of the human cell adhesion molecule CD2 at 2.5 A resolution. AB - BACKGROUND: The T-lymphocyte antigen CD2 is an adhesion molecule implicated in immune responses in vivo. The extracellular regions of the human and rat homologues of CD2 share only 45% sequence identity and bind different protein ligands. Comparison of the human and rat soluble CD2 (sCD2) structures should provide insights into the structural basis of cell surface recognition. RESULTS: We therefore determined the crystal structure of a form of human sCD2 with single N-acetylglucosamine residues at each glycosylation site to 2.5 A resolution with an R-factor of 19.3%. It is composed of two immunoglobulin superfamily domains similar to those of rat sCD2, but the relative orientation of the domains in the two homologues differs by up to 20 degrees. An interaction involving the flat, highly charged, ligand binding GFCC'C" faces of crystallographically related human sCD2 molecules duplicates, in a different lattice, that observed in the rat sCD2 crystals. CONCLUSIONS: Intramolecular flexibility appears to be a conserved feature of CD2. The head-to-head interaction between molecules represents a general model for interactions between adhesion molecules of this structural class. Ligand specificity may be influenced by the distribution of charged residues on the binding face. PMID- 7994577 TI - [Consanguinity and public health in Morocco]. AB - This study concerns the evolution of consanguinity in Morocco in its historical, religious, legal, and sociological context with regards to Moroccan customs and undertakes to evaluate its relationship to public health. Thus it attempts to specify if consanguinity, in its present state in Morocco, poses a problem for public health. With this goal in mind, methodology has been concentrated on two approaches. The first, based upon examination of documents and oral research interviews, has made theoretical assessment possible. The second, substantiated by the study of notarial marriage acts and the analysis of 4773 medical files concerning consanguineous marriages compiled throughout the seven regions of Morocco, has enabled us to specify the importance and the evolution of consanguinity and its impact on health. This study shows a marked decrease in consanguineous unions predominantly found in rural and mountainous zones and frequent between first cousins, especially the paternal cousin. From the medical standpoint, our study has revealed the absence of pathology in 97.13% of cases studied, the transmission of various gifts in 1.08% and that of degenerative traits in 1.79% of the descendants. Consequently, in our country, a country in perpetual evolution and in contact with the outside world, consanguinity which is disappearing of its own accord does not present a preoccupying problem for public health. Its future would seem to be limited to the relation between the physician and marriage partners in search of genetic counsel. PMID- 7994576 TI - Crystal structure of the amino-terminal fragment of vaccinia virus DNA topoisomerase I at 1.6 A resolution. AB - BACKGROUND: Vaccinia virus, a cytoplasmically-replicating poxvirus, encodes a type I DNA topoisomerase that is biochemically similar to eukaryotic-like DNA topoisomerases I, and which has been widely studied as a model topoisomerase. It is the smallest topoisomerase known and is unusual in that it is resistant to the potent chemotherapeutic agent camptothecin. RESULTS: The crystal structure of a 9 kDa amino-terminal fragment of vaccinia virus DNA topoisomerase I has been determined at 1.6 A resolution. The fragment forms a five-stranded, antiparallel beta-sheet with two short alpha-helices and connecting loops. Residues that are conserved between all eukaryotic-like type I topoisomerases are not clustered in particular regions of the structure. CONCLUSIONS: This is the first atomic structure of any region of a eukaryotic-like DNA topoisomerase I. It has provided insights into the structural bases of the phenotypes of some single-site mutants of the intact topoisomerase. The structure has enabled us to study the interactions within a well-folded protein fragment and the camptothecin resistance of the viral topoisomerase. PMID- 7994578 TI - [The four stages of drug addiction (based on clinical experience with 5,000 drug addicts)]. AB - A medical practitioner has been inquiring on the subject for eighteen years, and confronting the discrepancy between the facts observed and the social and psychiatric approach of the plague. His study of adolescent toxicomania was proceeding from the care of 1000 drug-fiends, plus a dialogue with 3000 schoolers and the interview of about one thousand drug-fiends on their way to recovery. Four stages have been made clear in the evolution of the disease. Stage 1- Contamination of 12 to 18 year-old-individuals, among whom 90% find a safe escape through mere self-defense (contamination from the cannabis "joint" in 95% of cases). Stage 2--Occasional users, one or two "joints", now and then, several times a month, for fun, out of submissiveness to a group or search for adventure or challenge. Stage 3--Regular use of one or several drugs entailing the spiral of dependency resulting in a distorted psyche, a disinterest in studies, marginality delinquency. Recovery is possible provided they give up the use of any drugs whatever thanks to firm ans understanding help from the family or and institution, avoiding any psychiatric response. Stage 4--Drud-fiends hooked to hard drugs such as cocaine, heroin, polytoxicomaniacs they have become the slaves of drugs, undergoing a severe physical and psychic decay, they feel lovely, consider drugs as they only friend, they have a suicidal behaviour. The immuno deficiency caused by drug-use makes intercurrent diseases likely to strike. Recovery is still possible through drastic weaning treatment, even under constraint since they endanger their own lives, and a 12 to 18 months treatment of remotivation as well as training for social reinsertion. The therapeutic community, well organized and governed, is able to provide low cost solutions to a plague that too often comes to a deadlock. Although we can't say that first and second stage teenagers are real drug-fiends, on the contrary, third and fourth stage patients have necessary gone through stage 1 and 2. It can't be denied that they suffer from the same disease. Stage 1 and 2 teenagers and cured patients don't show the psychic decay and suicidal impulse of stage 3 and 4 patients. Such symptoms are the result of the use of drugs and not its cause. Consequently the role of the narcotic product is prevailing in the evolution of the disease. PMID- 7994579 TI - [Prevention of nicotine addiction. Importance of education in the academic environment]. PMID- 7994580 TI - [Tuberculosis and HIV]. PMID- 7994581 TI - [The road accident is not inevitable]. AB - Doctors can play an essential role in the epidemiology of road accidents. Problems of vision are important and require new legislation as a result of recent studies. Fatigue, drowsiness and falling asleep among driver is recognized in approximately 30% of cases. Better information should take into account recent surveys underlining the frequency of this problem. The taking of licit or illicit drugs is a non-negligible factor in the loss of control of a vehicle during prolonged journeys, and is particularly aggravated by alcohol. Users, of whom there are many in France according to statistics, should be better informed about the risks, both by clear warnings on containers and by the prescribing doctors. Of all causes of accidents, those that are about to be discussed are among the most frequent. Their prevention should diminish road mortality, a veritable national scourge. PMID- 7994582 TI - [Visual information and road safety]. AB - The French authorities have recently decided that an eye-sight examination should be required for the delivery of a driving licence and also at a later date for confirmed drivers. This appeared to be necessary, because the impairment of driver's visual capacity is sometimes the cause, either directly or indirectly, of accidents. The visual information relies on the visual acuity but also on contrast sensitivity, the spatial perception, the color vision, the depth appreciation and the visual recovery after a glare. During twilight and during normal night driving with dipped-beam headlights, the luminance of the roadway is very low and reduces the efficiency of the functions indicated above. Other factors also appear to be unfavorable such as: old age, being tired and unreasonable drinking and use of drugs. The visual information of the drivers depends on the technical equipment of the road and more precisely on the general lighting of the most dangerous spots of heavy traffic roads. In order to reduce both the frequency and gravity of accidents, standards covering the minimal efficiency of each eye function are required, such as the choice of the specifications covering the eye examinations. PMID- 7994583 TI - [Fatigue, drowsiness and sleep]. AB - Vigilance is a critical output of adaptative processes related to sleep/wake continuity and circadian rhythms. Since vigilance is highly stressed in the modern technic society, its sudden failures, expressed as fatigue, drowsiness and/or sleepiness, may be dramatically involved in accident's incidence, as observed in work accidents, manufacturing and transport sectors and private life. There is a detectable human factor involved in 70% of cases. Even if there are multifactorial circumstances, human factor such as fatigue, overwork or errors in decision are generally reported. Two main cases may be described: on one hand sleepiness and fatigue occur as sleep deprivation builds up, with an excessive duration of wakefulness (that suggests that it may be prevented by information and hygienic precautions), on the other hand sleepiness is the expression of a sleep illness or disease (and it must be detected early by a clinical biological survey). Three levels are reviewed and discussed for a comprehensive view of abnormal fatigue and sleepiness: what is the prevalence as evaluated by epidemiologic, biologic and psychologic methods? is there any specificity of cognitive disturbances associated with intrinsic or rhythmic dyssomnic illness and how can one evaluate or measures them? on the basis of some experimental reports in normal subjects by changing wake and sleep schedules it is assumed that the recovery which follows a sleep deprivation may be quite different when there is an early or a late night sleep deprivation. Possibilities for self-sleep training are discussed. The actual great interest in abnormal sleepiness is supported by its human and socio-economic consequences. If new pharmacological or physiological treatments have recently be suggested, information and cooperation are required in healthy subjects and in patients. Self-detection in the course of sleepiness is a critical factor: it may be learned and taught by medical preventive projects. PMID- 7994584 TI - [Medication, narcotics and behavior at the wheel]. AB - Consumption of illicit drugs is generally underestimated as cause of road accidents. French legislation does not give the police authority to carry out their detection at once. If the regulation concerning driving and drinking is on the way of an hardening, a debate comes into being about the suppression of the penalization for consumption of some drugs whereas their involvement in road fatalities seems to be important. The influence of medicinal drugs on driver's behaviour forms the subject matter of many experimental studies, but the lack of a common methodology for testing their side effects prevents any possibility of categorization of the medicinal drugs depending of their risk for driving. This common methodology should include tests for the evaluation of risk taking and not only test for the detection of sedative effects. If self prescription and misuse of some medicinal drugs is often involved, if the prescription of some others should be allowed only for non drivers, it should be suitable to take into account the notions of therapeutical benefits and of preservation of social and professional integrity by the way of driving. PMID- 7994585 TI - [Morals, logic and ethics in reproductive medicine]. AB - Human reproduction has always been a matter of philosophical interrogations and controversies. This situation has been reinforced by the technical evolution which has occurred during the past years. Both hopes and concerns have been raised at the same time. Two recent advancements deserve consideration and are given as demonstrative examples: intracytoplasmic injection of spermatozoon, preimplantatory diagnosis. Their consequences are very important for both the medical and the philosophical approach. One of the questions which arises at this occasion is to determine if research on pre embryos is legitimate or not. This evolution has provoked some reluctancy and several criticisms concerning the future of the children obtained by such techniques: the risk of slippery slope, possibly leading to a form of eugenics, and the fundamental and philosophical problem of the status of the embryo. However, behind these discussions a deeper and heavier controversial matter may be discovered; it deals with the role and the responsibilities of the governmental power. An opposition does exist between two different perceptions: on the one hand, the concept of a powerful governmental body, responsible for the respect of a statutory law, grounded on a sort of universal ethical rule, to be followed by all, a concept which bears the risk of totalitarianism; on the other hand, the concept of a law with a limited responsibility to protect public order, allowing a normal social life. Amongst the numerous responsibilities of the governmental power, one is often neglected, everywhere; its concerns the protection of the female life and health. Some examples are given. However the most frightening risk, much more dangerous than the frequently alleged risk of biological eugenics, is what can be called "economical eugenics". Again some examples are given, in all the systems of social protection. Submitted to ethical rules imposed by political and legal powers, and to the influence of economical forces, what will be the role and the responsibilities of the practitioner? Unfortunately the answer may be obvious: the only way is leading to a relinquishment of medical responsibility. Far away from the dialogue which was the rule of the "dual relationship" between the patient and the practitioner, away too from the more complicated situation of today, characterized by the intervention of "third parties", the evolution, probably unavoidable, appears to be towards the withdrawal of the psychological, moral, human and humanistic involvement of the practitioner, leading him or her to a technical role.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 7994586 TI - [Functional exploration of brown adipose tissue using beta3 agonists]. AB - In view to utilize beta 3 adrenoceptor agonists for the investigation of body lipid metabolism, a study of the effects of BRL 37344 on the functional activity of the brown adipose tissue was performed in the Rat. It is known that this tissue is the principal site of heat production for nonshivering thermogenesis mainly due to the oxidation of fatty acids under the control of norepinephrine (NA) released from the sympathetic nervous system. In order to stimulate the activity of the tissue, rats were reared at 16 degrees C. When they were one month old, they were divided in two groups; one group received a surgical sympathectomy of the interscapular brown adipose tissue (TABI) (S group); the other group was sham-operated (T group). The resting metabolism was estimated by the continuous measurement of O2 consumption and CO2 release, at an ambient temperature of 25 degrees C. The animal capacity for nonshivering thermogenesis was determined by increased O2 consumption following i.p. administration of NA or BRL 37344. In the S group a large decrease in TABI NA content and a decrease in resting metabolism were observed. In both groups VO2 was increased by the two drugs; the increase was linearly related to the dose of BRL (between 2.5 to 10 micrograms/kg); but it was 3 times as high in the T group as in the S group. Moreover, the effect of BRL was 40 fold greater than the effect of NA. These results seem to indicate that, in cold reared rats, a part of nonshivering thermogenesis may be mediated by the beta 3 receptors of the brown fat. It may be concluded that the rats born in cold conditions are good models to study the role of beta 3 receptors in the energetic activity of this tissue very profuse in infant but not in adult man. PMID- 7994587 TI - [Pharmaceutical technology: development and research]. AB - Production of pharmaceutics cannot be compared to the manufacture of consumer goods: pharmaceutical manufacturing is the study and bulk manufacture of the ingredients from which medicines are made, and is concerned with the mixing, preparing, packing, of the ingredients into a dosage form for the patient, in according to the good manufacturing practices (GMP). Development and manufacture are not discrete activities but links in a single chain of activity. Research and development, pharmaceutical training, regulatory requirements: these concepts are present with three ways: bioavailability, targeting and compliance. PMID- 7994588 TI - [Potentiation of the photocytotoxic effect of photofrin II: synergistic action of verapamil and lovastatin]. AB - Photofrin II (P2) is at the present time the most used drug in the photochemotherapy of tumors. As previous studies from our group have demonstrated that P2 is taken up by cells mainly via the low density lipoprotein (LDL) receptor pathway, we tried to increase the amount of drug delivered to cells by enhancing the LDL receptor expression. For this purpose, we used hydroxy methyl glutaryl Coenzyme A (HMG-CoA) reductase inhibitors such as lovastatin. In the present work, we show that the calcium antagonist verapamil, which is currently used in human chemotherapy to overcome multidrug resistance, enhances in a synergistic manner the potentiating action of lovastatin on the photocytotoxic effect of P2. PMID- 7994589 TI - Preselection of patients with high TAG-72 antigen expression leads to targeting of 94% of known metastatic tumor sites with monoclonal antibody I-131-CC49. AB - We studied 18 consecutive patients with advanced colorectal cancer where primary tumors were preselected for high expression of TAG-72 antigen and who underwent a phase I radioimmunotherapy trial with an intravenously administered monoclonal antibody CC49, 20 mg, labeled with I-131 in amounts varying from 15 mCi/m2 to 75 mCi/m2. Whole-body images and SPECT of the abdomen obtained 1 week after infusion were compared with pretreatment CT scans. A total of 66 lesions were evaluated. SPECT revealed 2/66 lesions (3%) that were not detected by CT; 4/66 were only detected by CT: lungs (1.8 cm and < 1 cm), axilla (1.5 cm), adrenal (2.5 cm). Thus, based on immunohistopathological testing in paraffin-embedded tissue blocks of primary tumors stained for TAG-72 antigen, we have selected a subset of patients (about 70% of referrals) with colorectal cancer for whom I-131-CC49 was shown to target to 62/64 CT positive lesions (97%) and 62/66 (94%) of all known positive lesions. We conclude that in patients with significant TAG-72 tumor expression there is excellent targeting of I-131-CC49 in therapeutic doses to colorectal cancer with respect to lesions detected with CT scanning. It should be noted that this study was not designed as a comparison of the sensitivity of CT versus I-131-CC49 SPECT/planar imaging. Instead, the observed results are consistent with a biological hypothesis that in general, the primary tumor histology vis-a-vis TAG-72 expression reflects the TAG-72 expression of the metastatic sites. PMID- 7994590 TI - Computer model challenges breast cancer treatment strategy. AB - The breast cancer treatment failure rate remains unacceptably high. The current breast cancer treatment paradigm, based primarily on Gompertzian kinetics and animal models, advocates short-course, intensive chemotherapy subsequent to tumor debulking, citing drug resistance and host toxicity as the primary reasons for treatment failure. To better understand treatment failure, we have studied breast cancer from the perspective of computer modeling. Our results demonstrate breast cancers grow in an irregular fashion; this differs from the Gompertzian mode of animal models and thus challenges the validity of the current paradigm. Clinical and laboratory data support the concept of irregular growth rather than the common claim that human tumors grow in a Gompertzian fashion. Treatment failure mechanisms for breast cancer appear to differ from those for animal models, and thus treatments optimize on animal models may not be optimal for breast cancer. A failure mechanism consistent with our results involves temporarily dormant tumor cells in anatomical or pharmacological sanctuary, which eventually result in aggressive metastatic disease. PMID- 7994591 TI - Characteristics of local recurrence following lumpectomy for breast cancer. AB - We report the clinical characteristics and treatment of local breast relapse in our breast cancer patients who were initially managed with breast conservation surgery (lumpectomy) alone. A retrospective study was conducted of 366 patients who were treated since 1977. The clinical, pathological, and treatment data regarding the primary tumor and the recurrences (91) were reviewed. The actuarial rate of local breast relapse in this group was 31% at 10 years. Breast relapse was significantly less in those patients 65 years old or greater. Acceptable treatment of the breast relapse included total mastectomy or repeat lumpectomy plus radiotherapy. Most relapses were small and occurred in the same area as the original tumor and had similar histology and estrogen and progesterone receptor values. About one-third of patients will have isolated relapses after conservation surgery alone, but in the older age group, isolated breast relapse occurs less frequently. The recurrences are usually surgically resectable, and acceptable results can be achieved with salvage surgery. PMID- 7994593 TI - Laboratory correlates of chemoimmunotherapy with low-dose recombinant interleukin 2 and mitomycin C in patients with advanced carcinoma. AB - Based on our clinical findings that the ability of cancer patients to generate lymphokine-activated killer (LAK) cells was remarkably augmented after mitomycin C (MMC) administration, we designed a treatment regimen that consisted of MMC 12 mg/m2, i.v. on day 1 and recombinant interleukin-2 (IL-2) 700 U/m2, i.v. every 12 hr from day 4 through day 8. Of 29 patients with advanced carcinoma treated with this regimen, 10 had a partial response (PR) and 4 had a minor response. The correlation of hematological and immunological changes associated with this treatment with the antitumor response to this therapy was investigated. Pretreatment values of total white blood cell and lymphocyte counts, and the level of increase of eosinophil counts in responder patients who showed a PR, were significantly greater than those in nonresponder patients. However, there was no correlation between clinical response and cytotoxic activities of peripheral blood mononuclear (PBM) cells, including NK and LAK activity, and the ability to generate LAK cells after the treatment. The capacity of adherent cells in PBM to produce IL-1-beta was increased after the treatment in both responders and nonresponders, whereas IL-1-alpha production was not increased. In addition, a significant increase in the ability to produce TNF-alpha was observed only in responders, indicating the correlation of TNF-alpha production with clinical response to this therapy. Since these correlations had been reported in the previous studies using IL-2, the present results suggested that the therapeutic effectiveness of this therapy against advanced carcinoma, is due to IL-2 probably augmented by its combination with MMC. In addition, these parameters might be predictive of therapeutic efficacy of this treatment. PMID- 7994592 TI - High dose-intense chemotherapy alone or in combination with interleukin-2 for small cell lung cancer: a pilot study. AB - Given the antitumor activity of interleukin-2 (IL-2) against some drug-resistant cancer cells, 17 previously untreated patients with small cell lung cancer entered a pilot study to evaluate the feasibility, efficacy, and immunological effects of combining 12-week high dose-intense chemotherapy based on a modified Evans regimen (CAV/PE) with different IL-2 schedules (6-12 MU/m2 week as a 48-72 h infusion using the same cumulative dose, 72 MU/m2). Despite significant myelotoxicity, up to 70% of the intended dose intensity was delivered, showing no differences with regard to the IL-2 schedule used. Immunotherapy-induced toxicity was usually mild and manageable. No limiting effects were observed in patients receiving immunotherapy except for a very poor compliance to the 12-week IL-2 regimen. The low-dose 72-h infusion was the optimal IL-2 schedule. As given in this study, neither of the alternating CAV/PE regimens abrogated the effects of IL-2 on T-cell and NK-cell subsets, showing typical kinetics with rebound in lymphocytes following each discontinuation of the IL-2. While immunological changes cannot predict the antitumor effect of IL-2, they are consistent with those described for IL-2 alone, suggesting its compatibility with high dose intense chemotherapy. Although no definite advantages have been demonstrated in this small pilot study with significant unbalanced prognostic factors (12% 2-year survival), both the preserved immunostimulatory effects and the lack of limiting overlapping toxicity make this combined approach promising and worthy of further clinical investigation. PMID- 7994594 TI - Proteins binding to cisplatin-damaged DNA in human cell lines. AB - Cisplatin (CDDP) is a highly effective, frequently used cancer chemotherapeutic drug employed in the treatment of several human malignancies including ovarian, testicular, and bladder cancers. A common problem encountered with cisplatin therapy is intrinsic or acquired resistance to this drug. While the mechanisms of resistance to cisplatin, and other chemotherapeutic agents, are not fully understood, one factor affecting the cellular response to CDDP may result from differences in the level of specific proteins that recognize CDDP-damaged DNA. We have developed a damaged DNA affinity precipitation technique that allows the direct visualization and characterization of cellular proteins that bind to cisplatin-damaged DNA. In the present study we have utilized this method to analyze proteins present in several mammalian cell lines that bind to cisplatin damaged DNA. We demonstrate that HeLa cells, resistant to CDDP cytotoxicity, contain high levels of high-mobility-group proteins 1 and 2, which bind to CDDP DNA. We also show that xeroderma pigmentosum cells of different genetic complementation groups contain variable levels of a 45-kDa protein that binds to CDDP-DNA. Thus, our results indicate that different human cell lines demonstrate qualitative and quantitative differences in the expression of cisplatin-damaged DNA binding proteins. PMID- 7994595 TI - O6-methylguanine-DNA methyltransferase in normal and malignant tissue of the breast. AB - An important component of high-dose chemotherapy/autologous bone marrow support regimens for adjuvant treatment of breast cancer is carmustine. Preclinical studies have shown that the level of the DNA repair protein O6-methylguanine-DNA methyltransferase is correlated with the resistance of cultured human tumor cells to this drug, but little is known about transferase levels of breast tissue in vivo. We measured the DNA repair activity in 80 tissue samples from 65 patients, including normal, abnormal, benign, and malignant specimens. Wide interindividual variations was observed and average transferase levels were similar in normal and benign tissue. However, transferase levels were significantly elevated in stage I IV disease. In addition, the frequency of samples with no detectable transferase was greatly reduced in this malignant group, and transferase was positively correlated with the presence of positive nodes, a marker for disease progression. In contrast, transferase levels were not correlated with age or estrogen receptor status, and the levels in normal tissue did not vary between patients with benign or malignant disease. These results suggest that this DNA repair activity may be increased in breast cancer relative to normal tissue and encourage further study of the predictive value of transferase measurements in high-dose chemotherapy/autologous bone marrow transplant for breast cancer. PMID- 7994596 TI - Growth inhibitors against tumor cells in Cordyceps sinensis other than cordycepin and polysaccharides. AB - Cordyceps sinensis is a parasitic fungus that has been used as a Chinese medicine for a long time. In the present study, inhibitory effects of crude methanolic extracts of C. sinensis fruiting bodies on various tumor cell lines were demonstrated. The crude methanolic extracts were fractionated into 15 fractions by silica gel column chromatography. Two of the 15 fractions (CS-36-39 and CS-48 51) significantly inhibited the growth of K562, Vero, Wish, Calu-1, and Raji tumor cell lines. The inhibitory activities were not due to the polysaccharides, which have been removed in the extracting process. The polarities of these two fractions indicated that they were different from that of cordycepin. Therefore, it is suggested that tumor cell growth inhibitors, other than cordycepin and polysaccharides, are contained in C. sinensis. PMID- 7994597 TI - Hepatic metastatectomy for low-grade leiomyosarcoma: a case report. AB - A patient with multiple bilateral liver metastases from a gastrointestinal leiomyosarcoma underwent staged sequential metasta- tectomy and at 3 years is tumor-free. PMID- 7994601 TI - Trimetrexate: a critical appraisal of the phase II clinical trial experience: evidence of drug discovery-clinical development disjunction. PMID- 7994598 TI - Application of chemical immunomodulators to the treatment of cancer and AIDS. AB - A number of potential advantages, development of promising new agents, and the discovery of synergy with cytokines or cell products continue to spur research into the application of chemical immunomodulators for the treatment of cancer and AIDS. In preclinical in vitro and in vivo systems, chemical immunomodulators definitely modulate the immune system and have therapeutic efficacy. Although clinical trials have shown the ability of these agents to modulate the human immune system, thus far chemical immunomodulators have generally not fulfilled the therapeutic promise generated in animal models for the treatment of human diseases. While the discrepancy in results between animal models and human trials is obvious, the basis is not apparent. Species differences in elimination kinetics, presentation of active drug at the site of action, and the development of tachyphylaxis have been postulated as reasons for the minimal activity of these agents in humans. In addition, the use of investigational techniques established for cytotoxic agents may not be appropriate for immunomodulators. As with any immunomodulator, determining an optimal immunostimulatory dose and schedule and applying the therapy to patients with minimal tumor burden would perhaps be more appropriate than use of a maximally tolerated dose in patients with advanced disease. A dose-immunological effect relationship has recently been demonstrated for levamisole at doses higher than those used for many years in levamisole trials (99). While research and clinical investigation have identified several potentially useful chemical immunomodulators, the elementary understanding of the biochemical mechanisms involved in immunoregulation remains basic. Future research must elucidate these mechanisms, particularly in humans, to maximize the benefits of chemical immunomodulators as single agents or combined with cytotoxic chemotherapeutic agents, surgery, radiation therapy, other immunomodulators, and antiviral agents. PMID- 7994599 TI - Clinical progress in neuroblastoma. PMID- 7994600 TI - When regulatory requirements conflict with ethical study design: the case of oral ondansetron. PMID- 7994603 TI - Tamoxifen chemoprevention--are we throwing out the baby with the bathwater? PMID- 7994602 TI - Evidence-based recommendations against neoadjuvant chemotherapy for routine management of patients with squamous cell head and neck cancer. AB - The objective of this study was to determine appropriate recommendations for neoadjuvant chemotherapy in the treatment of head and neck cancer (HNC). Published reports of randomized trials of neoadjuvant versus standard therapy in patients with stage III and stage IV HNC were identified by literature search. The overall trial results were analyzed using three pooling techniques: vote count, weighted median survival, and meta-analysis of published survival data. Excluded from analysis were articles on intra-arterial therapy, studies without a standard treatment control arm, studies that included adjuvant therapy, and abstracts. Twelve studies were evaluable for vote count, 11 for weighted median survival analysis, and 10 for quantitative meta-analysis. By vote count there was no observed survival difference in 7 trials, a trend favoring control in 3, a statistically significant difference favoring control in 1, and a trend favoring neoadjuvant therapy in 1. The weighted median survival was 20.9 months for control versus 20.0 months for neoadjuvant chemotherapy, with consistent trends for resectable and nonresectable disease and for chemotherapy combinations versus single agents. The common odds ratios for deaths at 12, 24, and 36 months were 1.12, 1.27, and 1.11, respectively, all in favor of control treatment. Data generated using rigorous methodological standards indicate that neoadjuvant chemotherapy should not be offered to patients with locally advanced HNC if improved survival is the outcome of interest. It is premature to recommend neoadjuvant chemotherapy to preserve organ function, although patients should be aware of this option and the limitations of the current data. PMID- 7994604 TI - Multiple group II self-splicing introns in mobile DNA from Escherichia coli. AB - By PCR (polymerase chain reaction) amplification and cloning, we have identified four group II self-splicing introns encoding proteins related to reverse transcriptases in natural Escherichia coli isolates belonging to the ECOR collection. One intron, IntD, interrupts a DNA sequence virtually identical to that of the previously described IS3411 Insertion Sequence. A second intron, IntC, is located within an open reading frame that is closely related to a reading frame in the T-DNA of Agrobacterium tumefaciens. Finally, introns IntA and IntB are inserted at two distinct sites in one of the Rhs elements of E. coli. A comparison of their open reading frames shows that the two Rhs introns are more closely related to each other than to any other known group II intron: this suggests that transposition of group II introns may occur preferentially in cis, along the same piece of DNA. PMID- 7994605 TI - Differential expression of HLA-DRB genes according to the polymorphism of their regulatory region. AB - The polymorphism of the HLA-class II molecules is directly involved in the specificity of the antigen presentation. We have previously described an allelic polymorphism in the proximal promoter region of the HLA-DRB genes. In this study, we demonstrate that this polymorphism has functional consequences on the transcriptional activity of the promoter of the different DRB genes. Indeed, transiently transfected DRB gene promoters into human B cell lines showed a marked difference in their ability to induce transcription of the chloramphenicol acetyl transferase (CAT) reporter gene. These findings suggest the presence of two interdependent effects of the HLA-class II molecules on the specificity of the immune response: one corresponding to the allelic polymorphism of the peptide binding site and the second resulting from the polymorphism of the promoter regions inducing a variable expression of the DRB genes. PMID- 7994606 TI - Defective transmembrane calcium influx demonstrated in a primary immunodeficiency by video-imaging. AB - A rise of intracellular calcium concentration triggered by the engagement of various membrane receptors is a key event in the control of cell growth. This increase involves both a release of calcium from intracellular stores and the opening of a transmembrane calcium conductive pathway. Using video imaging to measure intracellular calcium concentration in individual fura-2-loaded cells, we detected a defect in calcium influx in lymphocytes and fibroblasts collected from patients affected by a rare and new form of primary immunodeficiency. In these cells, pharmacological agents such as thapsigargin or ionomycin, and the physiological activator bradykinin, only induced transient increases in cytoplasmic calcium level, due to the emptying of internal stores, while in control cells, this initial step is followed by an additional and sustained transmembrane calcium influx. The fact that calcium influx is absent in patient's fibroblasts indicates that the related deficiency, which is clinically associated with a lack of proliferation of T lymphocytes, also affects cells of the non hematopoietic lineages. This study emphasizes the adequacy of single cell imaging for determining whether some forms of pathologies are associated with a disregulation of ionic fluxes, and for identifying them accurately. PMID- 7994607 TI - [Myxomatosis in the sub-antarctic islands of Kerguelen, without vectors, thirty years after its introduction]. AB - Myxoma virus was introduced into the Kerguelen archipelago in 1955-1956. Thirty years after its introduction, the virus is present in most areas inhabited by rabbits. Rabbit fleas and mosquitoes are absent from this group of islands and the disease is transmitted by contact. The timing of the beginning of new myxomatosis outbreaks, the absence of real epizootics as well as the higher percentage of infected males over females are specific observations in favour of this mode of transmission. The majority of 34 isolates tested between 1984 and 1988 are of intermediate virulence (Grades IIIA-IIIB). In these conditions, the impact of myxomatosis virus on rabbit populations estimated on two sites is low. Myxomatosis therefore plays only a minor role in the regulation of rabbit populations. PMID- 7994609 TI - [Production of Leydig cell testosterone in mature rats: mechanism of action of the Sertoli paracrine factor]. AB - In Percoll purified Leydig cells from mature rat incubated in Ham F12/DME medium, we have demonstrated that the testosterone production (1 ng/10(6) Leydig cells/3 h) is increased 9 fold in presence of a saturating amount of oLH but diminished when larger doses of gonadotropin are used. However, if SCM or STM is added together with oLH to the Leydig cell incubation medium, a further increase (69%) of testosterone output is noticed. Obviously, when the testosterone production is low consecutive to a desensitizing dose of oLH, the STM or SCM improves at least 2 fold the steroid synthesis. Therefore, the paracrine factor (or factors) presents in SCM (or STM) which is testis specific and acts in synergy with dbcAMP and 22R-hydroxycholesterol, uses an alternative pathway to improve rat Leydig cell testosterone production since its biological effect is highly potent in absence and in presence of oLH. Therefore, these data bring new insights in the regulation of rat Leydig cell steroidogenesis through cAMP-independent channel suggesting either an increase of the cholesterol side chain cleavage activity and/or availability of the cholesterol to mitochondria. PMID- 7994608 TI - High variability of the gag/pol transframe region among HIV-1 isolates. AB - The overlapping region of gag and pol genes of human immunodeficiency virus type 1 (HIV-1) also called transframe region, contains the frameshift locus from gag to pol. This region encodes both the protein p6, the function of which remains unclear, and a putative transframe protein covently linked to the N-terminus of the viral protease within Gag/Pol protein precursor. We have investigated the variability of the transframe region among nine HIV-1 isolates obtained from Congolese AIDS patients. Nucleotide sequences were determined using the polymerase chain reaction and the direct sequencing of amplified products. The sequences of Congolese isolates markedly differed from one another and from other reference HIV-1 strains by both insertion-deletion events and numerous base substitutions. Several putative cleavage sites of precursor polypeptides were modified. When compared to consensus ones the amino acid sequences of p6 protein were very different among divergent HIV-1 isolates, except for a limited group of 10 conserved amino acids. PMID- 7994610 TI - High rate of movement of one (mdg3) out of four transposable elements in a natural population of Drosophila melanogaster. AB - We have analysed by in situ hybridization the insertion site polymorphism of the copia, mdg1, mdg3, and P transposable elements in diploid genomes of wild males from a natural population of Drosophila melanogaster. The values of observed average degree of individual heterozygosity for all elements except mdg3 deviate statistically from the values expected by site frequencies, revealing a tendency toward homozygosity as if drift or a structuration in the population was operating. The high degree of heterozygosity for mdg3 which in addition does not deviate from the expected value, suggests that recent high rate of movements has strongly countered the population host effect on this element. Hence, heterozygosity for TEs may well reflect the history of the population, and reveals temporary high rate of site movement existing in natural populations. PMID- 7994611 TI - Ex vivo culture of adult microglial cells from previously lesioned rat brains. AB - In an attempt to study more precisely the glial cells involved in reactions following specific brain injuries, we tried to culture cells derived from surgically-lesioned rat brains or adult rat hippocampus previously treated with kainic acid, a convulsant which induces status epilepticus associated with structural modifications. We find that, contrary to cultures derived from normal adult rat brain, cultures from lesioned rat brains can survive and proliferate in vitro. Characterization of the cell types using double labeling with isolectin B4 for microglia and GFAP antisera for astrocytes shows that cultures from KA treated adult rats consist of nearly 100% macrophagic-microglial cells, whereas those obtained from surgically-lesioned brains are composed of a mixed population of microglial cells and astrocytes. These models are proposed as suitable for the further study of microglial-neuronal interactions involved in brain damage and repair. PMID- 7994612 TI - Adjuvant activity of polar glycopeptidolipids of Mycobacterium chelonae (pGPL-Mc) on the immunogenic and protective effects of an inactivated influenza vaccine. AB - Mice injected intraperitoneally with 2.5 or 25 mg/kg of pGPL-Mc, before, during or after the administration of a monovalent inactivated influenza vaccine (8 IU of A/New Jersey/X53), exhibited significantly very high haemagglutination inhibition (HI) antibody titers (up to 8 fold) as compared to vaccine controls. Treatment with pGPL-Mc has increased the protective effect of the vaccine by completely abolishing, in certain treatment groups, the onset of symptoms of disease and mortality after a lethal challenge with 5 LD50 of A/PR/8/34 virus, 60 days after the first vaccination. Moreover, the development of visible pulmonary lesions significantly decreased in surviving vaccinated mice treated with 25 mg/kg of pGPL-Mc on day D0. These results suggest that pGPL-Mc is a potent adjuvant to the immunogenic and protective effect of inactivated influenza vaccines. PMID- 7994613 TI - Unintegrated HTLV-I proviral DNA in cell lines and uncultured peripheral blood mononuclear cells from tropical spastic paraparesis (TSP/HAM) and adult T-cell leukemia (ATL) patients. AB - Ultrastructural studies on cell cultures derived from TSP/HAM and ATL patients, show the presence of large quantities of HTLV-I viral particles in extracellular spaces and budding at the cytoplasmic membrane. In addition, mature enveloped particles and images of endopinocytosis of virions are seen in the cytoplasm vacuoles suggesting the existence of a reinfection phenomenon. In this context, we decided to investigate some features of the replicative cycle, in particular the synthesis of unintegrated proviral forms. To increase the sensitivity of detection, we applied a procedure which combines the electrophoretic separation of closed circular forms and PCR amplification. By this procedure we produced evidence for the existence of supercoiled HTLV-I DNA in established cell lines from TSP/HAM and ATL and in patients peripheral blood mononuclear cells. These HTLV-I unintegrated proviral forms may play an important role in the physiopathology of HTLV-I associated diseases. Preliminary results of AZT/interferon treatment in ALT patients are largely superior to chemotherapy. The therapeutic effect of AZT, it known inhibitor of reverse transcriptase, may be through its inhibition of the synthesis of HTLV-I unintegrated proviral DNA. PMID- 7994614 TI - A cryptic peptide of TRH prohormone inhibits TRH-induced GH release. AB - The effects of two cryptic peptides from pro-TRH: Ps4 (160-169) and Ps5 (178-199) were investigated on basal and secretagogue (GRH and TRH)-induced releases of GH from perifused fragments of rat adenohypophysis. Validation of the perifusion system was done by measuring: (1) the dose-dependent effect of GRH and TRH on GH release; and (2) the stimulation of that release by forskolin (to mimic the adenylate cyclase pathway) or by phorbol ester (to mimic the protein kinase C pathway). We show that: (1) Ps4 and Ps5 (1 microM) do not modify basal GH release; (2) Ps4 (1 microM) changes neither GRH (10 nM)- nor TRH (100 nM)-induced release of GH; (3) Ps5 (100 nM and 1 microM) significantly decreases the release of GH induced by equimolar concentrations of TRH but not that induced by GRH. PMID- 7994615 TI - [Relationship between irradiation and appearance of brain tumors in rats]. AB - Sprague-Dawley rats were exposed to Co 60 irradiation (3 Gy) at different ages. Rats were distributed among sham-control (618 males and 120 females) and exposed groups: foetus (66 males and 65 females), 3 month-old (304 males), and 9 month old (120 males and 60 females). The incidence of brain tumours was 5.3% in male control rats and nil in female control rats. Brain tumour incidence decreased in 9 month-old rats (3.3%), and increased from 6.6% in 3 month-old rats to 15.2% in male foetuses and 12.3% in female foetuses. Age at incidence of brain tumours decreased in irradiatiated animals. Astrocytomas were the more susceptible type of brain tumours to radiocarcinogenesis. PMID- 7994616 TI - Additive effects of calcipotriol and cyclosporine A: from in vitro experiments to in vivo applications in the treatment of severe psoriasis. AB - We report that calcipotriol (CPT) is a potent inhibitor of lymphocyte proliferation in mixed epidermal cell lymphocyte reactions. In this model, CPT and cyclosporine A (CsA) have synergistic effects. These results have led to a randomised double-blind therapeutic study protocol in patients with severe psoriasis. In these patients, topical CPT and sub-therapeutic doses of CsA (2mg/kg/d) induce disappearance of cutaneous lesions. This therapeutic association may minimize secondary side effects of both drugs. PMID- 7994617 TI - A catalytic antibody isomerizing a delta 5-3-cetosteroide. AB - Antibodies were raised against 3-fluoro-4-aza-estradiol-17-hemisuccinate to elicit abzymes capable of isomerizing delta 5-3-ketosteroids. The hapten was designed to present a planar A ring showing some analogy with the intermediate dienol and a polarity capable of inducing catalytic groups. Antibodies binding the hapten tightly were cloned and purified from either ascites or hybridoma supernatants. Catalytic activity was tested with androst-5-ene-3,17-dione. Among the five different monoclonal antibodies binding the hapten, one proved to enhance significantly the substrate isomerization rate (kcat/kuncat = 830). Initial rates followed Michaelis kinetics and the activity was competitively inhibited by the hapten. PMID- 7994618 TI - Amplification of myoadenylate deaminase during evolution. A comparative study. AB - Myoadenylate deaminase activity was measured, by using a specific assay technique, in a wide range of animal species, including four invertebrates, one cyclostome, 13 chondrosteans, one teleost and one mammal. The results are discussed considering the known genetic events that have lead to the appearance of the higher vertebrates myoadenylate deaminase molecular form. It is proposed that, during the extensive gene duplication that occurred in the beginning of vertebrate evolution, genetic modification of the myoadenylate deaminase molecule took place in at least two different taxa: the one that evolved to rajiform elasmobranch fishes and the other to the land vertebrates. PMID- 7994619 TI - On small genomes in eukaryotic organisms: molecular karyotypes of two microsporidian species (Protozoa) parasites of vertebrates. AB - Pulsed field gel electrophoresis (PFGE) was used to separate chromosome-sized DNA from two species of microsporidia of fishes. The molecular karyotype of Glugea atherinae exhibits 16 DNA bands from 420 to 2,700 kb, and that of Spraguea lophii 12 bands from 230 to 980 kb. Until now they represent respectively the largest and the smallest genomes visualized for microsporidia: 19.5 Mb for G. atherinae and 6.2 Mb for S. lophii (the smallest nuclear genome in eukaryotic organism). We have analysed separately five strains of G. atherinae (individual cysts), with this technique. The electrophoretic spectra are the same for these strains, except for the absence of the 2,380-kb band in one case. Therefore, the karyotype seems to be rather well conserved for this species. PMID- 7994620 TI - [Production of partial blastulas by parthenogenesis in Xenopus]. AB - In mature Xenopus eggs, the cell cycle can be triggered by pricking the egg or by an electric shock. However, no cleavage occurs unless centriole-containing fractions or isolated centrosomes are injected at the time of egg activation. We have obtained for an average of one heterologous centrosome injected per oocyte a complete parthenogenetic development. We also observed that the success rate of blastula formation declined linearly with the time elapsing between oocyte activation and centrosome injection. Moreover, in most cases, large areas of the blastulas remained uncleaved, interfering with gastrulation and blocking further development. PMID- 7994621 TI - Potentiation of 2',3'-dideoxycytidine (ddC) by hydroxyurea and thymidine on the Moloney murine leukemia virus (MoMLV) early replicative steps. AB - Combinations of ddC with either the ribonucleotide reductase inhibitor hydroxyurea (HU) or with the natural nucleoside thymidine have been investigated on the cycle of a defective (psi neo) Moloney Leukemia Virus (MoMLV) using 3T3 fibroblasts as host cells. In this experimental model, ddC displayed very poor antiviral action which was obvious given an IC50 value close to 100 microM, i.e. an efficiency about thirty thousand fold lower than that of AZT. Both HU and thymidine alone resulted in significant inhibition of MoMLV replication with IC50 values of 40 microM and 100 microM respectively. The combination of ddC with 50 microM HU lowered the IC50 of ddC by a factor of 10. A similar but more pronounced effect was obtained by combining ddC and 100 microM thymidine, which decreases the IC50 value of ddC by a factor of 50. Combining 40 microM ddC and 100 microM thymidine resulted in the quite complete inhibition of viral replication. These results show that in cell types with strongly restricted ddC action, combination treatment with compounds known to ultimately decrease dCTP biosynthesis leads to the restoration of efficient antiviral activity. PMID- 7994623 TI - Do microglial cells phagocyte the beta/A4-amyloid senile plaque core of Alzheimer disease? AB - We performed EM, immuno-EM and light microscope immunohistochemistry studies on the topographic and functional relationships between microglial cells and amyloid senile plaque core in Alzheimer's disease. Microglial cells with cytologic characteristics of phagocytic function were associated to amyloid fibrils and to other neuropathological degenerative processes. On the periphery of the amyloid plaque core, microglial cells contain intracytoplasmic bundles of membrane bound fibrils. These fibrils, like plaque core fibrils, are immunodecorated. Immunostaining was observed neither in secretory organelles nor in hyalaplasm. Preamyloid deposits in superficial layers were not associated to microglial cells. These data lead us to conclude that the microglial cells participate to phagocytosis of beta/A4 amyloid and do not secrete this substance in Alzheimer's disease. PMID- 7994622 TI - Hb Taybe (alpha 38 or 39 THR deleted): an alpha-globin defect, silent in the heterozygous state and producing severe hemolytic anemia in the homozygous. AB - Several alpha-chain hemoglobin variants have been described as responsible, in homozygous or compound heterozygous patients, for a chronic hemolytic disease that overlaps thalassemia and Heinz bodies hemolytic anemia phenotypes. These variants are present in trace amounts together with some Hb H in the lysate of the patients. In the asymptomatic heterozygous carriers, they are usually not detected by electrophoretic methods. Hb Taybe is an example of such an unstable and thalassemic alpha-hemoglobin variant. This hemoglobin was observed in a young Israeli Arab woman having suffered since birth from a severe and highly regenerative hemolytic anemia for which she was splenectomized at age sixteen. The structural abnormality was characterized by protein chemistry as the deletion of a threonine residue at position alpha 38 or 39 and assigned to the alpha 1 gene by selective DNA sequencing. This structural modification is localized in helix C, which is a highly conserved 3(10) helix participating in the alpha 1 beta 2 contact and close to the alpha 1 beta 1 interface. The propositus and two siblings, who were also anemic, were found to be homozygous for the molecular defect, although the abnormal Hb was not detected in the latters. Consanguinity in this family demonstrated the threshold effect in the clinical manifestations of such alpha-gene disorders since heterozygotes were clinically and biologically normal. PMID- 7994624 TI - [Value of linsidomine (SIN 1) in the evaluation of myocardial viability by 201-Tl scintigraphy after exertion]. AB - 201Tl scintigraphy can be used to determine exercise-induced ischemia and the viability of the hypoperfused myocardium as a function of radiotracer redistribution. Redistribution is calculated by differential analysis of the normalized circumferential curves of activity. Intravenous injection of linsidomine (SIN 1) a patent coronary vasodilatator, gives more reliable results than conventional imaging at the 4th h, and compares favourably with the results obtained at the 24th h after reinjection of 201 Tl. Linsidomine provides images in 60 to 90 min, in stable clinical conditions. PMID- 7994625 TI - [Receptors for the Fc fragment of IgG (RFc gamma): membrane forms and soluble forms]. AB - Membrane and soluble forms of Fc gamma receptors play important role in immune reactions. Upon interaction with immune complexes, Fc gamma R transduce activation or inhibition signals via their intracytoplasmic portions. Soluble Fc gamma R contain the Fc gamma R ectodomain. They bind to the Fc portion of IgG and inhibit Fc dependent immune reactions. In addition, they bind directly to various cell types and regulate immune reactions. PMID- 7994626 TI - [Interleukins and HIV disease]. AB - We characterised the effects of HIV infection on the production of Interleukins in lymphoid organs by studying the expression of the genes for two TH1 type Interleukins, IL2 and Interferon gamma, of two TH2 type Interleukins, IL4 and IL10, and of two proinflammatory Interleukins, IL6 and IL1 beta. Our results show, in benign hyperplastic lymph nodes, a hyperexpression of Interferon gamma by cytotoxic T8 cells, without increased expression of TH2 type or of proinflammatory Interleukins. In contrast lymphomatous lymph nodes are characterised by a paracrine hyperproduction of IL6 and an autocrine hyperproduction of IL10. PMID- 7994628 TI - [Eosinophil, beneficial or harmful: a cell entirely part of immune response]. AB - The demonstration that human eosinophils could express various membrane receptors (for IgG, IgE, IgA; for complement; for cytokines; for chemotactic factors), for adhesion molecules (VLA4, LFAI, OKM1), as well as CD4 and class II MHC, has allowed to reconsider the role of eosinophils in immune response. Indeed, eosinophils can function as antigen presenting cells and can be infected by HIV. Studies on eosinophil mediators have revealed that eosinophils are not only the source of cytotoxic and proinflammatory mediators but can also release various cytokines and growth factors, including their own factors of differentiation (IL 3, GM-CSF and IL-5). The recent observation that eosinophils expressed IgE binding molecules belonging to different gene superfamilies (CD23, Mac2/epsilon BP and FceRI), as well as two different IgA receptors (Fc alpha R, and secretory component binding site), participating both in antiparasite immune defence and in inflammatory processes, reinforces the concept of the functional duality of eosinophils, specially in tissues. PMID- 7994627 TI - [Phenotypic and functional characterization of human prothymocytes]. AB - We report herein the phenotypic and functional analysis of human bone marrow and thymus derived early T cells. Commitment to T cell lineage is acquired during CD7 antigen expression by CD34+ precursors in human bone marrow and before thymus colonization. Early thymocytes show similar phenotypic characteristics as bone marrow T cells. They rapidly acquire CD4 before the dual expression of CD4 and CD8. Their expansion and differentiation is regulated by two major factors: thymic stroma and cytokines produced by these stroma cells or by thymocytes themselves. Among cytokines, IL1 and sCD23 produced by thymic epithelial cells support in vitro early T cell development. PMID- 7994629 TI - [Cytokine synthesis: a new form of response of central neurons]. AB - This report provides the immunohistochemical demonstration of the appearance of tumor necrosis factor alpha and interleukin-1 alpha in neuronal cells of different regions of the brain after a surgical injury to the hippocampus. We also demonstrate, by an in situ hybridization technique using a digoxigenin labeled probe, the induction of TNF alpha mRNA in these neurons. Control lesions in brain areas such as the striatum, the parietal cortex or the cerebellum do not induce the neuronal expression of these cytokines. We hypothesize that cytokines production by neurons may be related with neurotrophin synthesis and restoration of homeostasis in an attempt to promote survival and regeneration of specific neuronal cell populations after a lesion to the hippocampus. PMID- 7994630 TI - [Molecular and cellular bases of the presentation of antigen and autoimmunity]. PMID- 7994632 TI - In vitro cytotoxicity testing for prediction of acute human toxicity. AB - This study was designed to compare the cytotoxic concentrations of chemicals, determined with three independent in vitro cytotoxicity testing protocols, with each other and with established animal LD50 values, and against human toxic concentrations for the same chemicals. Ultimately, these comparisons allow us to evaluate the potential of in vitro cell culture methods for the ability to screen a variety of chemicals for prediction of human toxicity. Each laboratory independently tested 50 chemicals with known human lethal plasma concentrations and LD50 values. Two of the methods used monolayer cell cultures to measure the incorporation of radiolabeled amino acids into newly synthesized proteins and cellular protein content, while the third technique used the pollen tube growth test. The latter is based on the photometric quantification of pollen tube mass production in suspension culture. Experiments were performed in the absence or presence of increasing doses of the test chemical, during an 18- to 24-h incubation. Inhibitory concentrations were extrapolated from concentration-effect curves after linear regression analysis. Comparison of the cytotoxic concentrations confirms previous independent findings that the experimental IC50 values are more accurate predictors of human toxicity than equivalent toxic blood concentrations (HETC values) derived from rodent LD50s. In addition, there were no conclusive statistical differences among the methods. It is anticipated that, together, these procedures can be used as a battery of tests to supplement or replace currently used animal protocols for human risk assessment. PMID- 7994631 TI - Sources of error associated with sample collection and preparation of nucleated blood cells for flow cytometric analysis. AB - Analysis of cellular DNA content by flow cytometry has been used to detect genetic changes associated with exposure to environmental contaminants. In lower vertebrates, nucleated red blood cells can be collected for analysis without harm to the animal. Because erythrocytes sampled from an individual should have identical amounts of DNA, the coefficient of variation (CV) around the G0/G1 peak should be small. Increases in CV can indicate genetic aberrations, but may also be caused by sample handling and preparation or problems with instrumentation. To increase confidence in associating increases in CV with external causes, artifactual changes in CV due to sample treatment and instrument parameters should be identified and minimized. We assessed the effects of various sampling and handling protocols on the CV of nucleated blood cells collected from largemouth bass (Micropterus salmoides). We also compared the distribution of cells among the G0/G1, S, and G2/M phases of the cell cycle to see whether these were affected by sampling or treatment protocols. Groups of 7 fish were bled on 7 consecutive days, and blood from each fish was analyzed by flow cytometry when freshly collected, and after freezing for 1 hour or 10 days. The same fish were bled again over a consecutive 7-day period, and the experiment was repeated. CV and cell cycle distribution were not affected by our freezing protocol. Repeat sampling from the same individual did not affect CV, but altered the distribution of cells in the cell cycle, suggesting increased hemopoiesis in response to blood sampling.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7994633 TI - Influence of rat strain on P-glycoprotein expression in cultured hepatocytes. AB - The amount and activity of the multi-drug transporter P-glycoprotein (Pgp) have been measured in cultured hepatocytes derived from different rat strains. A marked increase in Pgp, as revealed by Western blotting, occurred 48 h after seeding in hepatocytes from Sprague-Dawley, Wistar and Fischer 344 rats, the last showing the highest value. The addition of dexamethasone (DEX) to culture medium delayed Pgp overexpression in all the strains, proportionally to the protein amount in the absence of hormone. The R-123 functional test for Pgp showed that Fischer 344 hepatocytes had the lowest ability to extrude the fluorescent dye as compared with Sprague-Dawley or Wistar rats. These results suggest that the Fischer 344 rat is more prone than other strains to culture stressing conditions, leading to an overexpression of Pgp that is not necessarily functional. PMID- 7994634 TI - Derivation and characterization of a zebrafish liver cell line. AB - ZF-L cells were derived from normal adult zebrafish liver, and have been growing in culture for more than 100 generations. The cells were derived in basal nutrient medium supplemented with fetal bovine serum (FBS), trout serum, trout embryo extract, bovine insulin and mouse epidermal growth factor. After 50 generations in culture, optimal growth of the cells was achieved in medium supplemented with FBS (5%) and trout serum (0.5%). ZF-L cells were hypodiploid (modal chromosome number = 46) and exhibited an epithelial morphology. ZF-L cell homogenates exhibited alanine and aspartate aminotransferase, glucose-6 phosphatase and alkaline phosphatase enzyme activities. The cells synthesized and released several proteins into the culture medium, including a 70 kDa protein recognized by anti-bovine serum albumin IgG. PMID- 7994637 TI - [Gene therapy of cardiovascular diseases]. PMID- 7994636 TI - Antagonism of cadmium cytotoxicity by differentiation inducers. AB - Studies on the antagonism of toxicity can provide information about toxic mechanisms and suggest chemotherapeutic strategies. A rapid cell growth assay that measures the effects of test agents on the accumulation of cell protein (Shopsis and Eng, Toxicol. Lett. 1985;26:1) has been applied to studies of the antagonism of the cytotoxicity of cadmium. Exposure of Balb/c mouse 3T3 cells to 15 mumol/L Cd2+ for 24 h or 7 mumol/L Cd2+ for 48 h caused a 50% decrease in total cell protein. Zn2+ and selenite ion, antagonists of Cd toxicity in vivo, antagonized Cd2+ cytotoxicity when added in micromolar concentrations at the initiation of exposure to Cd2+. A diverse group of chemicals that can induce differentiation in vitro in cultured erythroleukemia and other cells were also found to antagonize the cytotoxic effects of Cd2+ to 3T3 cells. Dimethyl sulfoxide (DMSO), hexamethylene bisacetamide, N,N-dimethyl formamide, N-methyl formamide, dimethyl acetamide, hypoxanthine, hemin, ouabain, and sodium butyrate, when added to cultures simultaneously with Cd2+, each antagonized Cd2+ toxicity. These agents were used at concentrations equal to or lower than the concentrations at which they induce cellular differentiation. Other cytotoxicity assays and morphological studies confirmed these observations. DMSO added as much as 6 h after the initiation of a 24-h exposure to Cd2+ still protected cells; conversely, pretreatment of cultures with butyrate or DMSO for 24 h followed by their removal did not confer protection against subsequent Cd2+ challenge. Ethanol and methanol (noninducers of differentiation) did not antagonize Cd2+ cytotoxicity, and differentiation-inducing agents did not protect the cells from Zn(2+)- or Hg(2+)-induced cytotoxicity. DMSO treatment does not induce an increase in the concentrations of metallothionein or glutathione in these cells. PMID- 7994635 TI - Acute effects of smoking and high experimental exposure to environmental tobacco smoke (ETS) on the immune system. AB - Controversial results have been published on the immune response to cigarette smoking while the effects of exposure to environmental tobacco smoke (ETS) have not yet been reported. In a controlled study, acute effects of smoking and of a high environmental exposure to ETS on immunological parameters have been investigated. The study consisted of four experimental days, two control and two exposure days. On control days, 1 and 3, smokers (n = 5) and nonsmokers (n = 5) sat in an unventilated 45 m3 room for 8 h. On the exposure days, 2 and 4, each of the smokers smoked 24 cigarettes in 8 h, while the nonsmokers were exposed to the ETS generated by the smoking volunteers. Blood was drawn before and after each exposure session on all four experimental days for dosimetry of tobacco smoke exposure and determination of the immune response. Flow cytometry using monoclonal antibodies was used to determine CD3+ cells (whole T cells), CD19+ cells (B lymphocytes), CD16+ and CD56+ cells (natural killer cells), CD4+ cells (T-helper cells), CD8+ cells (T-suppressor cells), the CD4+/CD8+ (helper/suppressor ratio), and Fc receptors on granulocytes. Serum was analyzed for soluble CD14 receptors (sCD14), interleukin 1, interleukin 6 and prostaglandin E2 (PGE2). Functional stimulation assays were performed to determine the basal and induced level of reactive oxygen intermediate (ROI) production by polymorphic neutrophils. Exposure to tobacco smoke in both groups was confirmed by dosimetry of carboxyhemoglobin, plasma nicotine, and cotinine levels. In comparison to nonsmokers, smokers had elevated granulocyte cell counts, increased CD16+ and CD56+ cell levels and decreased CD3+ and CD19+ levels. Acute smoking, but not exposure to ETS, resulted in a slight decrease in the number of CD19+ cells and an increase in the number of granulocytes; the latter was restricted to one subject. Acute smoking and exposure to high experimental concentrations of ETS resulted in a slight increase in CD16+ and CD56+ cells. None of the changes determined in immunological parameters after either acute smoking or exposure to ETS reached statistical significance. Serum sCD14, cytokine and PGE2, functional stimulation of in vitro ROI production, and changes in Fc receptors were not affected by acute smoking or exposure to ETS. Although no clear guidelines exist to assess immunotoxicity in man, our data do not favor immunosuppression and the possibility of increased risk of infection in nonsmokers exposed to ETS under real-life conditions. PMID- 7994638 TI - [Refractory angina pectoris: clinical diagnosis and treatment]. PMID- 7994639 TI - [Inhibitory effect of interferon on expression of oncogene in over-proliferative smooth muscle cell]. AB - The model of balloon angioplasty (BA) was founded in rabbit abdominal aorta. In situ hybridization was used with the probes of oncogenes c-fos, c-myc and N-ras labeled by digoxin in vessel segments after BA and with the probes of oncogenes c fos, c-myc, and N-ras labeled by biotin in smooth muscle cell (SMC) irritated by cultured medium of vessel segments after BA. Overexpression of c-fos, c-myc and N ras oncogenes occurred in vessel segments after BA mainly in atherosclerotic plaques. There was expression of oncogene in normal vessel segments. Overexpression appeared in the over-proliferative SMC irritated by cultured medium of vessel segments after BA. A expression of N-ras occurred on the membrane of cellular nucleus. There was no expression of oncogenes in the normal SMC of control group. Overexpression could be partly inhibited by interferon gamma. PMID- 7994640 TI - [Accelerated thrombolysis by liposomal-encapsulated urokinase in a canine model of acute myocardial infarction]. AB - We prepared liposomal-encapsulated urokinases (LEUK) by detergent removal technique. The encapsulated efficiency of urokinase (UK) was 25.6%. The LEUKs were neutral large unilamellar vesicles and its average diameter was 60.4 +/- 13.6 nm under electron microscope. Measurements of UK activity indicated about 7.1% loss of activity or leakage in tris-buffered saline over a 48 hr period at a temperature of 4 degrees C. After the same time incubation of LEUK and UK in human platelet-poor plasma (PPP) at 37 degrees C, the percentage of UK activity in LEUK group was remaining higher than that of UK group (30 min: 84.3 +/- 3.0% to 46 +/- 4%; 60 min: 60 +/- 5% to 14.9 +/- 0.8%, P < 0.01). These results suggest that liposomes preserve the thrombolytic potential of UK and that the half-life of UK in liposomes prolongs more than two times. Canine model of acute myocardial infarction was based on a thrombos obstruction. Thrombolysis tests were compared for LEUK and UK (n = 5). The time for restoring vessel patency reduced more than 50% when compared with that in UK group (28 +/- 7 min to 69 +/- 7 min, P < 0.01). The total dosage of LEUK was correspondingly lower. After one hour thrombolysis, the fibrinogen of LEUK group (g/L) was considerably higher than that of UK group (2.5 +/- 0.5 to 1.6 +/- 0.4, P < 0.01). These results suggested that LEUK may be of practical significance in accelerating thrombolysis and reduction in bleeding complications. PMID- 7994641 TI - [Apolipoprotein B signal peptide insertion/deletion polymorphism in Chinese patients with coronary heart disease]. AB - Insertion/deletion (Ins/Del) polymorphism of the apo B gene encoding signal peptide and its relation to coronary heart disease (CHD) and lipid trait were studied in 103 patients with CHD and 100 healthy individuals from Chinese Han nationality. The frequency of rare Del allele was 0.259, which was significantly lower than 0.34 in Caucasians (France), but higher than 0.16 in South Asian descents in UK. When the frequency distribution of the Ins/Del alleles was compared between CHD group and control group, the frequency of rare Del allele in the patient group was not apparently different from that in the control group (0.282 vs. 0.235, P > 0.05). As for the impact of the Ins/Del genotype on levels of lipid and apolipoprotein, the patients with at least one Del allele had significantly lower HDL-C level compared with those with only Ins allele in the CHD group (P < 0.01). Levels of other lipid parameters in each group were not obviously associated with the Ins/Del genotype. It is suggested that the Ins/Del polymorphism of the apo B signal peptide might be involved in lipid metabolism by an unidentified mechanism in some ethnic population. PCR is a useful method for distinguishing Ins/Del polymorphism of the apo B signal peptide. PMID- 7994642 TI - [Mitochondrial DNA mutations in patients with myocardial diseases]. AB - Amplification of one of the frequently deleted regions of myocardial and lymphocytic mitochondrial DNA (mt DNA) from patients with dilated cardiomyopathy (DCM), acute myocardial infarction (AMI) and normal controls was carried out with polymerase chain reaction (PCR). The results showed that multiple deletions exist in mtDNA of both patients and normal controls. 7.8 kb deletion was detected in myocardial mtDNA of 2 patients with AMI and 10 patients with DCM; 7.47, 8.10, 8.32 and 8.48kb deletions were found in lymphocytic mtDNA of 3 patients with AMI and 25 patients with DCM as well as 14 normal controls. The incidence and abundance of the 7.47kb mtDNA deletion increased with age of all the subjects studied. Quantitative analysis showed that mutated mtDNA accumulated up to 10% of total mtDNA-only in some older patients. Single strand conformational polymorphism analysis of the amplified 8,530-9,333 fragment allowed us to find a point mutation in a patient with DCM. Clinical significance of the mutations in mtDNA was discussed. PMID- 7994643 TI - [Mitochondrial DNA mutation in Leber's hereditary optic neuropathy in China]. AB - Leber's hereditary optic neuropathy (LHON), a typical maternally inherited disease, is caused by a single nucleotide change of G to A at the site of nucleotide 11,788 of mtDNA. We used PCR method to analysis mtDNA from 102 individuals of nineteen pedigrees. The results showed that 67% of the patients (30/45) and 55% (29/53) of the maternal relatives have such a mutation, while no mutation exists in the four normal individuals. The results show that Wallace's mutation is a main cause of LHON in China. PMID- 7994644 TI - [Detection of a gene mutation in familial adenomatous polyposis families by PCR RFLP method]. AB - A simple and rapid PCR-RFLP method was used to detect a mutation hotspot of adenomatous polyposis coli (APC) gene. Among seven familial adenomatous polyposis (FAP) families, we found individuals in family FD carrying a mutated APC gene or a mutated APC allele with AAAGA deletion in codon 1,309 region. Two young affected persons in twenties were detected by screening the family FD kindred with this PCR-RFLP method. The results are in good accordance with those of colonoscopic examination. The PCR-RFLP method we established proves to be a reliable and simple technique for early detection of some FAP patients. The results indicated the existence of same kind of APC gene mutations in Chinese FAP families as those in western countries. PMID- 7994646 TI - [Comprehensive treatment for diabetes limb gangrene]. AB - Anisodamine was used to improve general circulation and the microcirculation of affected limbs. Measures like local debridement, dressing change, and control of diabetes were applied in 351 patients with diabetic limb gangrene. Of the 351 patients, 301 (85.7%) were cured, 27(7.7%) were improved, 7(2.0%) failed, 6(1.7%) had limb amputated, and 10(2.9%) died. In the treatment, the nail-fold microcirculation was markedly improved. Doppler scan showed increased width and bloodflow of the vessels of the affected limbs. The criteria for the classification and diagnosis of diabetes limb gangrene are suggested. PMID- 7994645 TI - [Sequencing of hepatitis B virus DNA fragment coding major HBsAg of escape mutant]. AB - We amplificated a HBV DNA fragment coding the major HBsAg from a chronic HBsAg carrier's serum with high titer of HBsAg and anti-HBs using polymerase chain reaction (PCR). The direct sequencing of PCR products revealed a single mutation from adnosine to guanosine at the nucleotide position 532 of HBV DNA of the escape mutant. This mutation might result in an amino acid substitution from threonine to alanime at the amino acid position 126 of HBsAg. Since this amino acid is located in the first loop of the "a" determinant of HBsAg, the mutation might result in an alteration of the structural antigenicity of the "a" determinant and induce escape mutant of HBV. PMID- 7994647 TI - [Experimental studies in effect of limb lengthening using metaphyseal osteotomy on epiphyseal growth plate]. AB - The experimental results in effect of limb lengthening using metaphyseal osteotomy at proximal tibia on epiphyseal growth plate in 28 young sheep were reported. Radiographic, microscopic and electronmicroscopic findings showed that lengthening of 7.5% the growth plate resulted in narrowing in varying degrees in one third of the sheep with a lengthening rate of 0.25 mm every six hours. Narrowing of epiphyseal growth plate was seen in half of sheep with lengthening of 10% and in all sheep with lengthening of 12.5% and 15%. Degeneration and necrosis of chondrocytes happened in one sheep of lengthening of 15%. Thickening of growth plate was seen in all sheep of the control group. Our conclusion from this series of experimental studies was that depression caused by compression stress effect in limb lengthening of less than 7.5% on epiphyseal growth plate is minimal. PMID- 7994648 TI - [Mechanism and prevention of hemolysis in jaundiced infants in phototherapy]. AB - It has been reported that the prolonged phototherapy results in decreased glutathione reductase (GR) activity in red blood cells. We found short-term phototherapy had the same side-effect. Besides it aggravates hemolysis of newborns during the therapy. This side-effect can be prevented by oral administration of Vit B2. Eighteen jaundiced infants who were given Vit B2 5mg three times a day during the phototherapy, and the control group of 16 patients were not given Vit B2. The results showed that the decrease of hemoglobin and the time of jaundice disappearance during the phototherapy were more favourable in the oral Vit B2 group than those of the control. These results indicated that the short-term phototherapy not only results in decreased GR activity in red blood cell, but also results in hemolysis of the newborn. This side-effect can be prevented by oral administration of Vit B2. PMID- 7994649 TI - [The effect of iron deficiency anemia on the auditory brainstem response in infant]. AB - Our study attempts to explore the mechanism by which iron deficiency anemia (IDA) affects the brain function of infants. We made auditory brainstem response (ABR) test for 48 IDA infants and 30 normal control infants, aged 6-36 months and reexamined ABR in 4 IDA infants after three months iron therapy. 26 cases of abnormal ABR among 48 IDA infants were found, it took 54.2% of total IDA infants. IDA led mainly to peripheral impairments of auditory system and rarely to brainstem. There was a direct relationship between the severity of IDA and the degree of abnormality of the ABR in infants. The threshold of ABR in IDA infants was significantly higher than that of in control group. It suggests that IDA infants have listening comprehensive difficulty as a result of impairment in high frequency hearing. After follow-up of 4 IDA infants, it was found that the impairment of auditory system could be reversible after prompt correcting of IDA. This observation has important significance for child health in the future. PMID- 7994650 TI - [Effect of BN52021 on platelet activating factor induced aggregation of psoriatic polymorphonuclear neutrophils]. AB - We investigated the aggregation of PMN from 20 psoriasis patients (PP) and 12 health persons (HP) to PAF and the effect of PAF antagonist BN 52021 on the aggregation. PAF induced a dose dependent aggregative response of polymorphonuclear neutrophils (PMN) from PP and HP. The aggregative responses of PMN from PP to lower concentrations of PAF were increased (P < 0.05) and to higher concentrations of PAF were not different to that of PMN from HP. BN 52021 could time- and dose-dependently inhibit the aggregation of PMN from PP and HP to PAF, and their IC50 was 1.3 x 10(-6) mol and 1.2 x 10(-6) mol respectively. It is suggested that PAF and PMN play an important pathophysiological role in the development of psoriasis, and application of PAF antagonists may be a new and effective approach to the management of psoriasis. PMID- 7994651 TI - [Ras genes and pancreatic neoplasms]. PMID- 7994652 TI - [Problems in the study of primary liver carcinoma]. PMID- 7994653 TI - [Summary of the workshop on chronic hepatitis, liver cirrhosis and liver carcinoma]. PMID- 7994654 TI - [Effects of selective hepatic duct embolization on normal, cirrhotic livers and hepatocellular carcinomas]. AB - Variant gross and pathology features were observed on effects of selective hepatic duct embolization (SHDE) in contrast to selective hepatic duct ligation (SHDL). Glue TH was used in SHDE that performed on normal liver, induced cirrhotic liver and hepatocellular, carcinoma. The results demonstrated that SHDL has weak effected, while SHDE causes the embolized liver lobes to acute ischemic necrosis, followed by atrophy and fibrosis, accompanied by quickly hypertrophy of the uninvolved lobes. All tumors on the embolized liver lobes also showed acute tumors on the embolized liver lobes also showed acute tumor ischemic necrosis, atrophy and fibrosis. The reason for the above variations is that pressure and tension of SHDE expand the embolized bile duct tree, especially the Hering duct, which will continuously obstruct the dual blood supply to the liver tumor. Effectively and thoroughly annihilating or restricting the tumor, SHDE may lead the tumors to "spontaneous excision", with the unoperated lobes hypertrophy to compensate liver functions simultaneously. These studies indicated that SHDE will be a new method in liver cancer clinic. PMID- 7994655 TI - [Combined treatment of hepatic carcinoma: percutaneous intratumoral injection of Y-90 glass treatment microspheres with sonographic guidance]. AB - Twenty-eight patients with hepatic carcinoma were treated with a percutaneous injection of Y-90 glass treatment microspheres (GTMS) with sonographic guidance. Of these patients, some were also given alcohol around the lesions and intraportal vein chemotherapy alternatively. Diagnoses were confirmed by biopsy in all patients preoperatively. All patients were alive after 2-16 months follow up. In this group, 91% patients had their tumor size reduced. All lesions showed changes in echo pattern on US scans after the treatment, most of them being hyperechogenic, then being mixed echogenic or isoechogenic. Blood flow sign decreased within lesions and at periphery on color Doppler scans. Of the 13 patients with increased AFP level before injection, 11 had AFP titer dropped with 6 falling to normal after treatment. All patients experienced relief of symptoms and improved general conditions. Histopathologic examination performed in 8 patients after treatment showed complete necrosis and fibrosis of the tumor in 7. Small focus of tumor tissue was detected in one patient only. The therapeutic outcome indicated that the percutaneous intratumoral injection of Y-90 is an appropriate first-line treatment for patients with hepatic carcinoma. PMID- 7994656 TI - [Distribution of pre-core A83 point mutation in hepatitis B virus infections]. AB - We designed a mispairing primer, which could introduce a Bsu36I restriction site into the amplified fragment of A83 mutant. Following PCR, the 102bp was diagnosed by the restriction endonuclease, and the variation was detected by demonstration of 82bp and 20bp bands on gel electrophoresis (RFLP). With the method, 77 cases of acute and chronic HBV infections were analysed. Among those, 31 (65%) mutants were detected in 48 anti-HBe-positive cases, and in 29 HBeAg-positive cases, 11 (38%) were co-infected with mutated and wild isolates. No pre C defect was found in acute hepatitis B and chronic asymptomatic carriers, suggesting that mutation occurs only after immune selection. The HBeAg defective variant appears to be involved in the loss of virus tolerance, and therefore in the pathogenesis of acute exacerbation of chronic carriage as demonstrated in this study. The various chronic liver diseases had an approximate mutation frequency, and it seems that A83 mutation nearly makes HBV infection persist. PMID- 7994658 TI - [Stress shielding and fracture healing]. AB - The influence of stress shielding after fracture fixation with plate on fracture healing was studied. The results of animal and biomechanical experiments as well as the clinical observations demonstrated that rigidity of the plate was not the only factor causing stress redistribution and stress shielding effects of bone. Either the internal fixation with different implants or external fixation with fixators all might lead to physical and chemical characteristic changes of bone tissue. In the early stage, the disturbance of blood supply and the bone structure remodeling may be the main reasons. Reaction to the implant was another cause in the middle stage. If the affected limb can take weight-bearing normally at late stage, the influences of plate on fracture healing mechanical properties of bone and the osteoporosis cause by stress shielding effects will become much less. The tissue of the affected limb was the most important factor which may cause osteoporosis and refracture. Osteoporosis, bone atrophy and immobilization syndrome of bone and joint can be prevented and treated by taking normal weight bearing and overcoming infection and implant reaction. PMID- 7994657 TI - [Roles of glutamate receptor in c-fos gene expression and epilepsy susceptibility in rats]. AB - We use NMDA to induce expression of c-fos mRNA as a marker to observe the activity of NMDA receptor in neurons during development, and compare the activity of NMDA receptor between audiogenic epilepsy -prone (P77PMC) and audiogenic epilepsy resistant rats brain. In primary culture of rats cerebral cortical neurons NMDA induced c-fos mRNA expression exhibits dose and time-dependent changes, which can be prevented by antagonists. During the development of neurons, the NMDA -induced c-fos mRNA expression reaches a maximum at day 24. NMDA-induced c-fos mRNA expression of P77PMC rats is higher than that of controls during 6 to 24 days in vitro with significant difference (P < 0.05) at day 18. To present changes in c-fos mRNA expression induced by NMDA in cultured P77PMC rat cortical neurons may be one of the factors related to susceptibility of epilepsy in P77PMC rats. PMID- 7994659 TI - [Immunoglobulin bearing cells and complement 3 in periodontal diseases]. AB - Frozen gingival tissue sections from marginal gingivitis (MG), juvenile periodontitis (JP), adult periodontitis (AP) patients and clinical healthy subjects (H) were immunohistochemically stained with specific antibodies to aid in identification and quantification of different Ig bearing cells in inflammatory infiltrates. IgG, IgA, IgM, K and lambda were present in all specimens studied. The numbers of Ig cells in disease groups were much greater than in H group, especially the IgG cells. The numbers of IgG cells in AP and JP were most abundant, followed by MG and H. The correlation between the number of IgG cells and the percentage of infiltrated connective tissue was obtained by linear correlation analyses (r = 0.534, P < 0.001). This means that the inflammatory infiltration became heavier as the number of IgG cells increased. It is the new finding that the number of IgA cells was smaller than the IgM cells in JP, the IgA/total heavy chains ratio was much lower than other groups. The C3 deposition was found in all of the gingival specimens. In healthy gingival tissue, C3 mainly deposited in both of the surface of inflammatory cells and vessels. In diseased status C3 located not only in these two, but also in sulcular (pocket) epithelium and oral epithelium, Igs were also observed in these areas. It is suggested that immunocomplex may deposit in gingival tissue. PMID- 7994660 TI - [The multiple tumor suppressor genes in human esophageal cancer]. AB - The mutation and deletion of the multiple tumor suppressor genes, including p53, Rb, APC and MCC in the same tissue of humanesophageal cancer (EC) and adjacent non-tumor were analysed by PCR amplification and direct sequencing. In 10 cases of EC 6 were found mutations of p53 gene, 5 were found abnormality of Rb gene, 3 were found mutation of APC gene, 3 were found mutation of MCC gene, 8 were found atleration abnormality of tumor suppressor genes Rb, p53, APC and MCC, 6 were found two or more abnormality of the tumor suppressor genes. The results indicated that the alterations in multiple of tumor suppressor genes were related to carcinogenesis of human esophageal cancer. PMID- 7994661 TI - [7 elements in patients with heart diseases and their relationship with blood pressure and biochemical target]. AB - The trace elements Zn, Cu, Fe, and ordinary elements K, Na, Ca, Mg in serum of 711 patients with heart disease (HD) were determined with GGX-II atomic absorption spectrophotometer and flame photometer. It was found that the contents of K, Ca/Mg in HD were significantly lower than those in the control, while the content of Na, Mg, Zn, Fe, and Zn/Cu, Na/K were significantly higher than those in the control. There was a significantly negative correlation between K, Ca/Mg and blood pressure (BP), between Zn/Cu and HDL-ch, and a significantly positive correlation between Na, Zn, Fe, Zn/Cu, Na/K and BP, between Fe and Hct, between Zn/Cu and Hct, TG, VLDL-ch. PMID- 7994663 TI - [Determination catecholamines levels in amniotic fluid, maternal and umbilical blood]. AB - Catecholamines (CA) levels of amniotic fluid, maternal and umbilical blood were determined by HPLC. The results showed that epinaphrine (E) and dopamine (DA) levels of pregnancy were significantly different as compared with non-pregnant women (P > 0.05), where as norepinephrine (NE) levels were significantly decreased (P < 0.05). In vaginal delivery, CA levels of pregnant women were significantly higher than those of non and late-pregnant women (P < 0.01). Plasma CA levels of umbilical artery were higher than those of umbilical vein (P < 0.001); NE of CA was 3.3 times, E 4.7 times and DA 2.1 times. NE and E levels of umbilical artery in cesarean section were significantly lower than those of in vaginal delivery. In fetal distress, plasma NE and E levels of umbilical artery were higher significantly than those of the normal fetus. CA levels of amniotic fluid increased with advance of gestational weeks, significantly in fetal distress, even more than the upper limit of 95%. The incidence of newborn asphyxia was about 60.0%. PMID- 7994662 TI - [Molecular screening and prenatal diagnosis of the deletional alpha-thalassemia by polymerase chain reaction amplification]. AB - For the genetic counselling, 8,432 blood samples from Chinese couples were screened for detecting alpha-thalassemia in Guangzhou city. The positive diagnosis of 646 (7.66%) alpha-thalassemia patients was made. One hundred DNA random samples from the above positive cases were collected and were analysed by using polymerase chain reaction (PCR) to determine the genotype of alpha thalassemia of Southeast Asian deletion(--SEA/). Of 100 alpha-thalassemia individuals screened for the (--SEA/) mutation, 99 (96 with alpha-thalassemia trait and 3 with hemoglobin H disease) were detected by the present method. This mutation was not found in the remaining one with alpha-thalassemia compound Hb Q. We also used this assay to analyse DNA samples from cord blood in 6 pregnancies at risk of Bart's hydrops fetalis, in 1 at risk of Hb H disease for prenatal diagnosis. PMID- 7994665 TI - [Macrophage-modulated loosening of joint prosthesis in later stage]. PMID- 7994664 TI - [Fluorescent in situ hybridization]. PMID- 7994666 TI - Verapamil improves left ventricular filling and exercise performance in hypertensive and normotensive elderly individuals. AB - OBJECTIVE: To study the effect of verapamil slow release (SR) upon left ventricular diastolic function and exercise capacity in newly diagnosed older hypertensive subjects compared with normotensive elderly and young controls. DESIGN: Cross-sectional prospective trial. INTERVENTIONS: Doppler echocardiography at rest and graded maximal exercise testing (with breath-by breath gas analysis) before and 4 h after administration of oral verapamil SR 240 mg, and before and after 12 weeks of daily medication. MAIN RESULTS: Verapamil administration normalized resting blood pressure in the older hypertensive group, but did not alter blood pressure in older normotensive or young groups. Resting heart rate was not altered in any of the groups. Both the older hypertensive and normotensive groups showed improvement in measures of diastolic filling after verapamil ingestion. Specifically, the older hypertensive group showed significantly faster isovolumic relaxation time (IVRT). In the older normotensive group IVRT was not changed, but the E:A ratio (the ratio of early to late peak transmitral flow velocity) was increased after verapamil. No differences were observed between the effects of verapamil after acute ingestion (4 h) or with chronic use (12 weeks) in any of the variables measured. In the younger group diastolic filling was not altered after verapamil ingestion. In both the elderly normotensive and hypertensive groups maximum oxygen consumption was significantly improved following verapamil ingestion. Again, no differences were observed between 4 h and 12 weeks. In the younger subjects exercise performance was not changed after verapamil ingestion. CONCLUSIONS: Verapamil SR improved left ventricular diastolic function and exercise performance in hypertensive and normotensive elderly individuals. Verapamil normalized blood pressure in the hypertensive subjects, but did not alter blood pressure in the normotensive elderly or younger subjects. PMID- 7994667 TI - Critical stenoses of the left anterior descending artery: predominant role in stress-induced pulmonary uptake of 201thallium. AB - OBJECTIVE: To relate the diagnostic finding of stress-induced pulmonary uptake of 201thallium to the severity and site of stenoses in specific coronary arteries. DESIGN: An ad hoc series of 525 referred cases had planar myocardial perfusion scintigraphy studies within four months of correlating invasive studies; patients who had previous revascularization procedures were excluded. MEASUREMENTS: Invasive studies were read by a cardiovascular radiologist with rating of stenoses as percentage luminal diameter, and grading of ventricular function from 1 (normal) to 5 (globally hypokinetic). Lung:myocardial ratios were quantitated independently on immediate poststress 201thallium myocardial perfusion images by a nuclear medicine physician. Multivariate regression equations were used to relate pulmonary uptake to stenoses in specific arteries and to the degree of ventricular dysfunction. RESULTS: Lung:myocardial ratios showed only a minor relationship to the number of subcritical (less than 90%) stenoses, but were considerably increased when severe (at least 90%) stenoses were present. Severe stenoses in the left anterior descending artery (LAD), particularly its proximal portion, provided the most dramatic increase in this index, modified by the contrast ventriculography score and to a lesser extent by additional stenoses at other sites. Regression analysis suggested a weighting of lesions in the LAD or left mainstem by a factor of at least 3 in comparison with the right coronary and left circumflex arteries. CONCLUSIONS: Stenoses in the LAD, particularly its proximal position, play a key role in the induction of increased pulmonary uptake of 201thallium on poststress scintigrams. PMID- 7994668 TI - Change in atrial volume following restoration of sinus rhythm in patients with atrial fibrillation: a prospective echocardiographic study. AB - OBJECTIVES: To determine if restoration of sinus rhythm in patients with atrial fibrillation decreases atrial size, 16 patients undergoing elective cardioversion were prospectively studied. The frequent coexistence of atrial fibrillation and atrial dilation is well recognized. Recent data have demonstrated that atrial enlargement may be the result, rather than the cause, of atrial fibrillation. DESIGN: Echocardiographic examinations were performed before cardioversion, and at 24 h, three and six months of follow-up. Atrial dimensions were assessed in multiple orthogonal imaging planes and atrial volume was calculated using an ellipsoid formula. SETTING: A tertiary care university teaching hospital. PATIENTS: All patients admitted to hospital between June 1989 and June 1990 for elective cardioversion were considered for enrollment. Informed consent was obtained in all cases. Patients were excluded if echocardiographic images were technically inadequate or reversion to normal sinus rhythm was not achieved. Twenty-five patients were considered for inclusion. The final study population consisted of 16 patients. Complete follow-up data were obtained in 10 cases. MAIN RESULTS: Conversion to sinus rhythm resulted in a decrease in mean left atrial volume from 38.5 cm3 to 34.2 cm3 (P < 0.01) at 24 h, 21.7 cm3 (P < 0.02) at three months and 19.6 cm3 (P < 0.02) at six months. Mean right atrial volume decreased from 33.4 cm3 to 29.4 cm3 (P < 0.01) at 24 h, 19.1 cm3 (P < 0.02) at three months and 16.3 cm3 (P < 0.02) at six months of follow-up. CONCLUSIONS: Conversion from atrial fibrillation to sinus rhythm results in a significant decrease in both left and right atrial volumes. PMID- 7994669 TI - Thrombolysis from P values to public health. PMID- 7994671 TI - Aqueous flare increase after light exposure in age-related macular degeneration. AB - An increase in anterior chamber flare is associated with many ocular conditions, including retinal diseases. We assessed anterior chamber flare in 18 patients (19 eyes) with exudative age-related macular degeneration using the Kowa flare-cell meter immediately before and 1 hour after exposure to 40 light flashes at a flash intensity of 300 W/s delivered with a Topcon fundus camera. Fourteen eyes showed a significant increase in flare 1 hour after light exposure (T = -3.452, p < 0.003, t-test). A second measurement in a subgroup of 10 patients exposed to 40 light flashes at a flash intensity of 36 W/s showed no significant change in flare 1 hour after light exposure. Multiple analysis of variance (two-way interaction) showed a highly significant difference between the two groups (F[1,27] = 8.66, p < 0.0066). We discuss possible mechanisms that may have produced these changes as well as implications of light exposure in various diagnostic and therapeutic settings. PMID- 7994670 TI - Fifty:fifty poly (DL glycolic acid-lactic acid) copolymer as a drug delivery system for 5-fluorouracil: a histopathological evaluation. AB - Fifty:fifty poly (DL glycolic acid-lactic acid) copolymer (PGLA) is a potentially useful depot drug delivery system for 5-fluorouracil (5-FU). The purpose of this study was to evaluate the fibroinflammatory reaction induced by this polymer. Polymer discs without 5-FU were inserted subconjunctivally in one eye of each of two guinea pigs and four pigmented rabbits (control group), and discs containing 20% 5-FU were inserted subconjunctivally in both eyes of nine pigmented rabbits (study group). The tissue reaction to the copolymer did not differ between rabbits and guinea pigs, with a mild mixed inflammatory reaction 1 week after implantation. At 2 weeks a thin fibrous capsule surrounded the discs, with no change in the amount of inflammation. At 4 weeks the disc had disintegrated, but residual polymer was seen within multinucleated giant cells in the episcleral tissue. Granulation tissue and inflammatory responses were mild. Less inflammation and fibrosis occurred in the study eyes, although the pattern of response was similar in the two groups. The inflammatory response to PGLA was markedly less than that to implanted collagen shields, and our findings suggest that PGLA implant is a promising ocular drug delivery system for 5-FU after filtration surgery. PMID- 7994672 TI - Visual acuity, refractive and keratometric results of 140 consecutive radial keratotomy procedures. AB - We reviewed the results of the first 140 consecutive radial keratotomy procedures (83 patients) performed by one surgeon from March 1986 to April 1992. The mean follow-up time per eye was 9.9 (standard deviation [SD] 9.1) months. The mean preoperative spherical equivalent refraction of -3.74 (SD 1.70) dioptres decreased by a mean of 2.75 D (SD 1.11 D) to a postoperative mean refraction of 0.99 D (SD 1.50 D). The postoperative uncorrected visual acuity was 20/40 or better in 120 eyes (86%). All eyes had a postoperative best corrected visual acuity of 20/40 or better. Correction to within +/- 1 D of emmetropia occurred in 98 eyes (70%), and no overcorrection of more than 1 D occurred. The mean amount of corneal flattening, as determined with keratometry, was 2.68 D (SD 1.23 D). Of the 42 eyes with high myopia (-4.50 to -9.12 D) preoperatively 57% had uncorrected vision of 20/40 or better postoperatively, and 31% had correction to within +/- 1 D of emmetropia. The corresponding figures for the 39 eyes with moderate myopia (-3.25 to -4.37 D) were 100% and 82%, and for the 59 eyes with low myopia (-1.00 to -3.12 D) 98% and 90%. There were no vision-threatening complications. The only significant loss of best corrected visual acuity occurred in one eye (1%) that lost two Snellen lines. PMID- 7994673 TI - Effect of timolol vs. acetazolamide on sodium hyaluronate-induced rise in intraocular pressure after cataract surgery. AB - This prospective study was done to compare the efficacy of timolol and acetazolamide in lowering the intraocular pressure (IOP) secondary to the use of sodium hyaluronate (Healon) in cataract surgery. Fifty patients undergoing extracapsular cataract extraction and implantation of a posterior chamber lens were randomly assigned to one of four treatment groups: no viscoelastic (10 patients), Healon with 0.5% timolol drops postoperatively (12 patients), Healon with acetazolamide postoperatively (16 patients), or Healon only (12 patients). The IOP was measured during the first 24 hours after surgery. Sodium hyaluronate caused a marked increase in IOP in the early (6 to 12 hours) postoperative period. Timolol proved to be more effective than acetazolamide in controlling this pressure increase. PMID- 7994674 TI - Ultrasound biomicroscopic features of pigmentary glaucoma. AB - We have developed a device capable of producing subsurface images in eyes at microscopic resolution. We call this method "ultrasound biomicroscopy." We examined 19 patients with pigmentary glaucoma or pigmentary dispersion syndrome using ultrasound biomicroscopy. Ten patients were found to have concave irides with small distances between the back of the iris and the zonule. In these patients iris-lens contact was greater than in patients without iris concavity and healthy patients. Nine patients did not show iris concavity or increased iris lens contact. The finding of iris concavity and increased iris-lens contact is compatible with a theory of reverse pupil block producing intermittent iris zonule touch, with a valve effect preventing posterior flow of aqueous. This theory was supported by the loss of concavity following iridotomy in three patients. The force that produces a reversal of the normal pressure gradient remains unclear, but recent evidence suggests that accommodation plays a major role. The patients who did not show iris concavity and increased iris-lens contact may have been examined at a time when these forces were not acting or had ceased to act. PMID- 7994675 TI - Pleural malignant mesothelioma metastatic to the orbit. PMID- 7994676 TI - Adenoviral keratoconjunctivitis precipitating Stevens-Johnson syndrome. PMID- 7994677 TI - Stargardt's disease and hemoglobin SC retinopathy. PMID- 7994678 TI - Repeated anterior chamber paracentesis for the treatment of central retinal artery occlusion. PMID- 7994679 TI - Euthanasia and physician-assisted suicide. PMID- 7994680 TI - Euthanasia and physician-assisted suicide. PMID- 7994681 TI - Medicine and health care: marital status uncertain. PMID- 7994682 TI - Medicine and health care: marital status uncertain. PMID- 7994683 TI - Medicine and health care: marital status uncertain. PMID- 7994684 TI - Medicine and health care: marital status uncertain. PMID- 7994685 TI - Paging medical interns. PMID- 7994686 TI - An open letter to Dr. Garson Romalis. PMID- 7994687 TI - Who are the recession-proof wealthy? PMID- 7994688 TI - Variations in the use of health care services: why are more studies needed? PMID- 7994689 TI - The Canadian Childhood Cancer Control Program. PMID- 7994691 TI - Toxicology: studies in drug safety. Interview by Alex Robinson. PMID- 7994690 TI - Variations in hysterectomy rates in Ontario: does the indication matter? AB - OBJECTIVES: To examine variations in rates of hysterectomy for the five main indications for the procedure in regions of Ontario. DESIGN: Cross-sectional population-based analysis of hospital discharge abstracts. SETTING: All acute care facilities in Ontario. PARTICIPANTS: All 65,599 women whose hospital record contained a procedure code indicating that a hysterectomy was performed between Apr. 1, 1988, and Mar. 31, 1991. Duplicate cases, records of cancelled procedures and nonresidents were excluded. MAIN OUTCOME MEASURES: Crude and age-adjusted rates of hysterectomy, by indication, for each region of Ontario. RESULTS: Five indications accounted for more than 80% of hysterectomies performed. The median age-adjusted rate of hysterectomy for Ontario regions during the study period was 6.25 per 1000 women, with a 2.7-fold variation among regions. The regions with rates of hysterectomy in the highest quartile tended to be rural, and those with rates in the lowest quartile tended to be urban areas with teaching hospitals. When rates of hysterectomy for specific indications were examined, they showed substantial variations among regions in the rate of the procedure for menstrual hemorrhage (18-fold variation), uterine prolapse (9.3-fold) and endometriosis (6.3-fold). A smaller but still significant variation was shown in the rate of hysterectomy for leiomyoma (2.3-fold). Regional variation in the rate of hysterectomy for cancer (2.5-fold) was not statistically significant. CONCLUSIONS: There are large interregional variations in rates of hysterectomy, especially for indications that are more discretionary than others (i.e., menstrual hemorrhage, uterine prolapse and endometriosis) and less variation in rates when treatment options and diagnosis are clear-cut. This result suggests the need for more definitive practice guidelines on treatment of the indications for which the rate is more variable. PMID- 7994692 TI - Physical activity and obesity. PMID- 7994694 TI - Reorganization of Canada's hospitals likely to have major impact on MDs, consultant says. PMID- 7994693 TI - No stone left unturned at Montreal hospital's clinical research unit. PMID- 7994695 TI - Medicare a noble but doomed experiment, University of Toronto dean says. PMID- 7994696 TI - Many scientific advances highlighted at 63rd annual meeting of Royal College. PMID- 7994697 TI - The soap opera of hospital life. PMID- 7994698 TI - Poster honours insulin's four discoverers. PMID- 7994699 TI - Reporting animal abuse. PMID- 7994700 TI - The veterinarian and animal welfare. PMID- 7994701 TI - An ethicist's commentary on the case of whether a biting dog should be adopted out or destroyed. PMID- 7994702 TI - Efficacy of tylosin tablets for the treatment of pyoderma due to Staphylococcus intermedius infection in dogs. AB - Tylosin tablets (20 mg/kg, q12h) were administered orally to 21 dogs with superficial or deep staphylococcal pyodermas. Response to therapy was excellent in 90.5% of the dogs, and in vitro susceptibility testing correlated perfectly with therapeutic response. Duration of therapy varied from 17 to 91 days, with an average of 33 days. Relapses occurred in 28.6% of the dogs within a three-month period. No side effects were reported. Under the conditions of the study, tylosin was an effective and safe antibiotic for the treatment of staphylococcal pyoderma in dogs. PMID- 7994704 TI - Femoral fractures in the newborn calf: biomechanics and etiological considerations for practitioners. AB - The etiology of femoral fractures in calves during assisted parturition was examined from the perspective of biomechanical force analysis. Femurs were collected from newborn calf cadavers. Their physical dimensions of length, cortical thickness, and diameter were measured from radiographs, and the data were recorded. The bones were then frozen until tested. The thawed bones were compressed axially in a materials testing machine until they broke, whereupon the breaking strength of the bones at the failure site was recorded. Fracture locations were documented radiographically, and the cortical thickness and bone diameter at the fracture site were determined. Fracture configurations and locations were similar to those found in clinical cases associated with forced extraction. The breaking strength of all femurs fell within the magnitude of forces calculated to be created when mechanical devices are used to assist delivery during dystocia. An etiology based on wedging of the femur in the maternal pelvis and resulting compression during forced extraction is suggested to account for the occurrence of supracondylar fractures of the femur of calves delivered in anterior presentation using mechanical devices in a manner commonly performed by veterinarians and owners. It is recommended that care should be exercised to correct or rule out the possibility of premature engagement of the calf's stifle into the birth canal, and thereby reduce the frequency of this type of fracture occurrence in the field. PMID- 7994703 TI - Lymphocytic enteritis and systemic vasculitis in sheep. AB - Lymphocytic enteritis and systemic lymphocytic vasculitis may be a new or previously unrecognized syndrome in sheep suffering from chronic wasting. Seven cases in three separate flocks were seen over an eight-year period at Veterinary Laboratory Services in Brighton, Ontario. Most of the animals were between five and twelve months of age and exhibited weight loss and inappetance, with or without diarrhea. All were Suffolks or crossbred Suffolks. In one of the flocks, there were also several sheep with lymphoma. Postmortem examination of carcasses and ancillary testing did not reveal an etiology; however, the intestinal and vascular lesions resembled those described in certain viral diseases, such as malignant catarrhal fever and Border disease, and immune-mediated diseases, such as polyarteritis nodosa. Submission for necropsy of sheep that exhibit signs of chronic wasting is encouraged, to help establish the etiology of the disease and its significance to the industry. PMID- 7994705 TI - A comparison of two methods for surveying mortality of beached birds in British Columbia. AB - Systematic surveys of beached birds are often limited in their ability to classify the causes of death of the carcasses recovered. Two methods of determining the cause of death of seabirds encountered during surveys of beaches of southwestern Vancouver Island, British Columbia, are compared. Birds were either subjected to external visual examinations by volunteer beach surveyors or submitted for gross postmortem examination by a veterinarian. The reliance on external examination of birds on beaches often prevented the accurate classification of the reproductive status and cause of death of the birds collected, but was valuable for describing the species, locations, and numbers of birds affected. The use of gross postmortem examinations of carcasses allowed for a more refined classification of the cause of death, as well as providing reliable descriptions of the bodily condition and sex of the birds examined. However, almost one half of the carcasses encountered were unsuitable for necropsy because of scavenging and decomposition. It is concluded that a combination of field and necropsy observations provides a useful method with which to monitor the pattern of mortality of beached seabirds. PMID- 7994707 TI - A severe outbreak of mucosal disease in central Alberta. PMID- 7994706 TI - Titers to Leptospira species in horses in Alberta. AB - Sera from horses in Alberta, submitted to Agriculture and Agri-Food Canada for routine testing for equine infectious anemia from January 1987 to June 1989, were tested for antibody against 13 serovars of pathogenic Leptospira spp., using the microscopic agglutination test. The purpose of the study was to investigate the prevalence of serum titers to those serovars in horses in Alberta, and to analyze the associated risk factors. Descriptive statistics were compiled and logistic regressions were computed. Titers to L. interrogans serovars icterohaemorrhagiae, bratislava, copenhageni, and autumnalis were common (94.6%, 56.6%, 46.5%, and 43.5%, respectively). The prevalence of titers to other serovars ranged from 0.8% to 27.2%. Age was almost always significantly associated with the presence of titers. In general, the chances of being seropositive rose by approximately 10% with each year of life. Horses managed individually (eg, track horses) were approximately half as likely to be seropositive as were horses managed in groups (eg, rodeo horses). PMID- 7994708 TI - Evaluation of two qualitative enzyme immunoassays for the rapid assessment of progesterone in equine plasma. PMID- 7994709 TI - Congenital cutaneous papillomatosis in a one-year-old Holstein. PMID- 7994710 TI - Diverticula of the urinary bladder in a juvenile dog. PMID- 7994711 TI - Solar dermatitis in hatchery-reared salmonids in British Columbia. PMID- 7994712 TI - Neospora-induced congenital myelitis and polyradiculoneuritis in a one-month-old Holstein calf. PMID- 7994713 TI - Anesthesia safety through monitoring. PMID- 7994714 TI - Prince Edward Island. Papillomatous digital dermatitis in a Canadian dairy herd. PMID- 7994717 TI - Dr. Kee Jim 1994 Schering Award recipient. PMID- 7994715 TI - Ontario. A condition resembling terminal ileitis in mature ewes. PMID- 7994716 TI - An ethicist's commentary on the found dog cases. PMID- 7994718 TI - Assessing the outcomes of veterinary education. PMID- 7994719 TI - Clinical and research applications of real-time ultrasonography in bovine reproduction: a review. AB - Transrectal real-time ultrasonography has proved to be a rapid and reliable technique for studying reproductive functions in cattle. Through ultrasonography it is now established that follicular growth occurs in wave-like patterns during each estrous cycle. It has been shown that follicular growth and regression continue during early pregnancy, as well as in the postpartum anestrous period. Ultrasound has also helped us to understand the influence of dominant follicles on medium and small follicles. Among the numerous demonstrated applications of ultrasonography, early pregnancy diagnosis, fetal sexing, and postpartum reproductive management appear to be promising areas for immediate application. The new information that has been generated through ultrasound has thrown light on hitherto poorly understood areas of ovarian follicular dynamics, corpus luteum function, pregnancy establishment, and embryonic development in cattle, thereby opening newer areas for research. Still there is great potential for the continued application of this technology to further our understanding of the reproductive processes and to maximize reproductive efficiency of the bovine species. The significant contributions of real-time ultrasonography to the study of bovine reproduction in general and its practical applications in particular are discussed in this paper. The need for taking up technology assessment studies and for the introduction of low-cost portable equipment are stressed. Literature search for this review was done by scanning Current Contents Series 1991-92, AGRICOLA 1980-92, and MEDLINE 1990-92. PMID- 7994721 TI - Pyelonephritis in a pronghorn antelope. PMID- 7994722 TI - Bilateral vital pulpotomies as a treatment of a class 2 malocclusion. PMID- 7994720 TI - The occurrence of Haemophilus somnus in feedlot calves and its control by postarrival prophylactic mass medication. AB - Three field trials were conducted in a large commercial feedlot in Saskatchewan to determine the prevalence of Haemophilus somnus in calves and to evaluate the efficacy of prophylactic mass medication with long-acting oxytetracycline on day 17 (1990, n = 1336), day 11 (1991, n = 4372), or day 8 (1992, n = 5632) postarrival. Hemophilosis accounted for > 40% of the mortality in feedlot calves each year. Haemophilus somnus was cultured from the blood of one febrile calf on day 1 (0.1%, n = 895), but it was not cultured from nasal swabs on day 1 or day 11 (n = 881) or from blood samples on day 11 (n = 883). Similarly, it was not cultured from nasal swabs or blood samples from sick calves first treated for bovine respiratory disease (BRD) (n = 219). Serological titers to H. somnus increased (p < 0.05) in unvaccinated calves from day 1 (Geometric mean titer = 11,846) to day 96 (Geometric mean titer = 63,712), indicating natural infection following feedlot entry. Calves that relapsed twice with BRD or died from BRD +/- hemophilosis had significantly (p < 0.06) lower titers to H. somnus on days 1 and 96 than those that did not relapse twice or die. Postarrival mass medication with long-acting oxytetracycline did not reduce (p > 0.05) the risk of hemophilosis mortality. However, it reduced (p < 0.05) the risk of BRD treatment by 14% and the risk of BRD mortality by 71%. Additional epidemiological studies of H. somnus are needed so that we can develop strategic medication and vaccination programs to reduce losses from hemophilosis. PMID- 7994723 TI - Intravenous anesthetic induction in small animal patients. PMID- 7994725 TI - The proper use of medical codes for dental procedures--Part 2. PMID- 7994724 TI - Hepatitis C: no longer a diagnosis by exclusion. PMID- 7994726 TI - The osteotome technique: Part 3--Less invasive methods of elevating the sinus floor. AB - Previous articles in The Compendium (February 1994, April 1994) described the features of the osteotome technique. In the initial article, a procedure that uses osteotomes to elevate the floor of the sinus, called the osteotome sinus floor elevation (OSFE), was mentioned. This article provides details and case reports on the OSFE. An enhanced version of the OSFE in which bone is added to the osteotomy will also be presented. The author concludes that the OSFE and the bone-added OSFE techniques are suitable means of altering the floor of the sinus so that in many patients, longer implants can be inserted in a less invasive manner. PMID- 7994727 TI - Multiple myeloma presenting with amyloid purpura and macroglossia: a case report and literature review. PMID- 7994728 TI - The diagnosis and treatment of discoid lupus erythematosus with oral manifestations only: a case report. AB - A case of discoid lupus erythematosus with oral manifestations only is presented. The patient complained of painful palatal ulcers that limited her dietary intake. A topical therapeutic regimen using plastic carriers containing clobetasol propionate was beneficial in significantly relieving the oral discomfort. The clinical and microscopic differential diagnoses for this mucocutaneous disease are also discussed. PMID- 7994730 TI - Diagnosis of periodontal diseases. AB - This article provides an overview of currently available periodontal diagnostic methods. It also addresses several prototype test kits undergoing in-office evaluations. Diagnostic techniques are critically evaluated in light of current concepts regarding the etiology and pathogenesis of periodontal disease. Furthermore, suggestions are made with regard to strategies for using multiple diagnostic assays. PMID- 7994729 TI - Management of periodontitis with oral-care products. PMID- 7994731 TI - New amalgam restorative techniques using phase-transition cementation. PMID- 7994732 TI - Research in dental caries in the United States: 1820-1920. PMID- 7994733 TI - Tooth-colored posterior restorations using Cerec Method (CAD/CAM)-generated ceramic inlays. AB - The ability to provide patients with esthetic tooth-colored posterior restorations produced from "factory-standardized" ceramics in a single visit is a unique feature of CAD/CAM technology. Recent improvements in the hardware and computer software of the Siemens CEREC CAD/CAM System have improved its ease of use and the quality of the restoration produced. Attention to tooth preparation requirements and care in the cementing and finishing procedures remain requirements for the production of these restorations. PMID- 7994734 TI - Dental lasers: safe or sorry? AB - The promise of laser dentistry has not yet been fully realized because too little science exists to support so much hyperbole. Each of the available dental laser systems has unique considerations regarding efficacy, safety, advantages, and disadvantages that may differ with any proposed dental procedure. Well-controlled clinical studies with multipotential improved systems may facilitate the introduction of lasers into general dental use. PMID- 7994736 TI - Inoue balloon, mitral valve. PMID- 7994735 TI - The background of dental school applicants: or, would you want your child to be a dentist? PMID- 7994737 TI - Hemodynamics of mitral stenosis: a review. AB - This review discusses the latest developments in the hemodynamics of mitral stenosis. English-language journal articles, reviews, and textbooks from the clinical, physiology, and engineering literature related to mitral valve stenosis were identified and reviewed. The main conclusions are: (1) the hemodynamics of mitral stenosis are determined by the complex anatomical and pathophysiologic features of the valve apparatus, (2) the properties of the left ventricle, atrium, and pulmonary vasculature also have a major impact on the hemodynamic significance and the clinical syndrome of mitral stenosis, (3) the valve and the cardiac chambers have a functional reserve that become exhausted as the stenosis worsens and/or the compensatory mechanisms of the chambers fail, and (4) a careful approach to data acquisition and analysis will lead to an accurate assessment of the hemodynamics of mitral stenosis before and after therapeutic interventions. PMID- 7994738 TI - Hemodynamic results, clinical outcome, and complications of Inoue balloon mitral valvotomy. AB - Percutaneous transvenous mitral commissurotomy (PTMC) was performed in 290 patients enrolled from 16 clinical centers in the United States and Canada. The mean age was 54 +/- 15 years and the mean total echocardiographic score was 7.3 +/- 2.8. Mitral valve dilatation resulted in an increase in mitral valve area from 1.0 +/- 0.3 to 1.7 +/- 0.6 cm2 (P < 0.001). Technical success, defined as final mitral area > or = 1.5 cm2 or a > or = 50% increase in area, was achieved in 83% of patients. Significant complications included mitral valve replacement in the hospital 1.0% and hospital death in 1.4%. Failure to cross the mitral valve occurred in 1.7%. Other complications that did not interfere with discharge from the hospital with a completed PTMC procedure occurred in 12.1% of patients. Among patients with successful PTMC, the valve area remained constant over a 24 month follow-up period. Although a minority of patients were NYHA Class I or II prior to PTMC, > 80% remained in Class I or II throughout the 2-yr follow-up period. The overall results in this registry demonstrate that the acute hemodynamic results of the procedure are excellent, the incidence of procedure related complications is acceptable, and a majority of patients remain symptomatically improved during a 2-yr follow-up period. PMID- 7994739 TI - Technique of percutaneous transvenous mitral commissurotomy using the Inoue balloon catheter. AB - Percutaneous transvenous mitral commissurotomy (PTMC) with the Inoue balloon has had increasing use internationally since its introduction in 1984. This device was designed specifically for mitral commissurotomy and differs substantially from conventional large diameter peripheral arterial or valvuloplasty balloon catheters. It is constructed of two layers of latex with a nylon mesh in between. The latex is extremely compliant, whereas the nylon mesh limits the maximum inflated diameter of the balloon and also gives it a unique shape and set of inflation characteristics. The balloon inflates in three stages. The front half inflates first, creating the appearance of a balloon flotation catheter. The proximal half of the balloon inflates next, creating an hourglass shape. When straddling across the valve, this allows self-positioning of the balloon. Finally, the center portion inflates, resulting in commissurotomy. The technique of commissurotomy involves introducing the balloon into the left atrium over a guidewire and then passing it into the left ventricle with the distal portion of the balloon inflated in a manner analogous to crossing the tricuspid valve with a pulmonary artery flotation catheter. Thus a guidewire is not used to enter the left ventricle with this technique. Increasing inflation volumes allow a single balloon catheter to be inflated to a variety of sizes, allowing stepwise dilatation of the mitral valve in a manner analogous to coronary angioplasty. This report describes the performance of this technique in detail, with practical approaches to many common problems encountered during PTMC. PMID- 7994740 TI - Percutaneous balloon mitral valvuloplasty: issues involved in comparing techniques. AB - A variety of techniques have been developed for performing percutaneous balloon mitral valvuloplasty. Two approaches, the Inoue catheter and double-balloon technique, have had the widest application. The Inoue procedure is technically simpler, with shorter fluoroscopy and procedure times. Acute hemodynamic results are excellent for both procedures, which result in significant reductions of left atrial pressure, transmitral gradient, and increases in mitral valve area. Although minimal randomized data are available, cumulative data from worldwide observational studies suggest postprocedure mitral valve areas may be slightly higher with the double-balloon technique. However, multicenter registry studies suggest a higher incidence of procedural complications with the double-balloon technique. The relative long-term efficacy, complications, and incidence of repeat mitral valve procedures are unknown and likely will never be resolved without a randomized trial. In summary, both Inoue and double-balloon techniques are suitable for performing percutaneous balloon mitral valvuloplasty. The Inoue catheter has clear advantages in terms of technical ease of operation and likely lower complication rates. The possibility of systematically obtaining slightly larger mitral valve areas with the double-balloon technique cannot be ruled out. PMID- 7994741 TI - Pathology of mitral commissurotomy performed with the Inoue catheter: implications for mechanisms and complications. AB - Pathologic findings were analyzed in 11 patients who had undergone percutaneous transvenous mitral commissurotomy (PTMC) from 1986 to 1992. Nine valves were obtained at mitral valve replacement and two were obtained at necropsy. These 11 specimens represented all cases studied pathologically among 96 patients undergoing PTMC at a single institution (St. Elizabeth's Medical Center) over this time period. Valvuloplasty was performed using a single balloon in three patients, double balloons in three patients, and the Inoue balloon in five patients. Regardless of the balloon used, fracture of commissural fusion was found to be the fundamental mechanism of success for PTMC. Conditions leading to failure of PTMC included inability to cross the valve, incomplete fracture of commissures, and severe subvalvular disease. Complications included hemodynamically significant atrial septal defect (ASD) and mitral regurgitation (MR). Etiology of MR included failure of leaflet coaptation, ruptured leaflet, and torn chordae, commissure, or papillary muscle. In this selected group of patients, no cases of left ventricular perforation were observed regardless of the technique employed. Hemodynamically significant ASD was observed only with standard single- and double-balloon techniques. MR, restenosis, and failed PTMC were observed with both standard and Inoue techniques. PMID- 7994742 TI - Complications related to percutaneous transvenous mitral commissurotomy. AB - Recent randomized studies have demonstrated that percutaneous transvenous mitral commissurotomy (PTMC) has similar efficacy compared to surgical commissurotomy. Compared with surgery, PTMC is associated with shorter hospital stays, reduced patient discomfort, and significantly lower costs. The challenge of PTMC remains to provide increased safety. The most serious risks of balloon commissurotomy include cardiac perforation and embolic stroke. The creation of severe mitral regurgitation also limits the effectiveness of the procedure and occasionally leads to the requirement for emergency mitral valve replacement. Since 1986, procedure-related mortality has ranged from 0-2.7% with lower mortality rates reported recently. The most frequent cause of procedure-related death has been left ventricular (LV) perforation. This is almost exclusively a complication associated with the double balloon technique, which requires LV guidewires. Cardiac perforation due to inadvertent atrial perforation during transseptal catheterization may occur with the Inoue technique as well, but this tends to be less severe and has not resulted in death. Embolic stroke has occurred in 1.1 5.4% of cases. The incidence of embolic events has been favorably influenced by routine preprocedure transesophageal echocardiography (TEE), eliminating patients with left atrial thrombi. Significant mitral regurgitation occurs in 3.3-10.5% of patients undergoing balloon mitral commissurotomy. Fortunately, mitral regurgitation infrequently requires emergency surgery (0.3-3.3% of cases). Iatrogenic atrial septal defects are usually of no clinical consequence. Their frequency has been reduced with the use of the Inoue balloon catheter system and they rarely require surgical repair.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7994743 TI - Acute and chronic efficacy of percutaneous transvenous mitral commissurotomy: implications for patient selection. AB - Despite the introduction of penicillin and improvements in the standard of living and delivery of primary health care, rheumatic mitral stenosis remains an important medical problem in the United States as well as abroad. In the past decade, percutaneous transvenous mitral commissurotomy (PTMC) with the Inoue balloon catheter has emerged as a safe and efficient treatment for symptomatic patients and has supplanted surgical commissurotomy as the initial treatment approach in the majority of patients with mitral stenosis. Acutely, balloon valvuloplasty can achieve an approximately 100% increase in mitral valve area and markedly improve symptoms, including dyspnea and NYHA functional class. However, peak oxygen consumption during exercise may not increase acutely, and the subjective improvement in dyspnea is likely related to a diminished work of breathing. Chronically, the hemodynamic improvements achieved with PTMC are maintained (up to 5 yr) with a low rate of recurrent symptoms due to restenosis, production, or progression of mitral regurgitation or inadequate initial dilation. Freedom from death, mitral valve replacement, and repeat valvuloplasty range between 51% and 84% at 4-5 yr postprocedure, depending on various selection criteria. Functional improvement, as measured by exercise capacity with respiratory gas analysis, occurs over several months suggesting that chronic peripheral alterations in the skeletal muscle and vasculature of patients with long-standing mitral stenosis may limit the initial benefit of successful PTMC until vascular remodeling or aerobic training can allow the skeletal musculature to use the greater cardiac output afforded by successful PTMC. Careful patient selection is essential to obtain the best hemodynamic improvement with the lowest rate of complications.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7994745 TI - Percutaneous transvenous mitral commissurotomy: a comparison to the closed and open surgical techniques. AB - Percutaneous transvenous mitral commissurotomy, first described in 1984, has gained acceptance as a mode of treatment for patients with symptomatic, severe rheumatic mitral stenosis. The closed surgical technique, one of the oldest cardiovascular surgical procedures, is similar in mechanism to the percutaneous technique. Nonrandomized and randomized trials are reviewed and percutaneous transvenous mitral commissurotomy compares favorably with the closed technique, both in acute hemodynamic changes as well as in long-term result. Although the percutaneous technique is quite different from the open surgical technique, comparisons are appropriate since this is the technique of choice in most industrialized countries. Randomized trials comparing the open versus the percutaneous technique have limited numbers of patients and follow-up, but preliminary data would suggest that the two techniques compare favorably in appropriately selected patients. It appears that percutaneous transvenous mitral commissurotomy has a definite place in the treatment of appropriately selected patients with symptomatic rheumatic mitral stenosis performed in experienced centers. PMID- 7994744 TI - Role of echocardiography in mitral commissurotomy with the Inoue balloon. AB - There are well-defined roles for echocardiography in the evaluation of patients with mitral stenosis who undergo percutaneous transvenous mitral commissurotomy. Transthoracic echocardiography is used to assess mitral valve morphology with particular attention to commissural fusion and valve leaflet calcification, the two most important determinants of the severity of mitral stenosis. This assessment has proven to be useful in patient selection, as immediate and long term outcome can be predicted from echocardiographic grading scores. The degree of mitral regurgitation can also be assessed and has an influence on outcome. The newer technique of transesophageal echocardiography aids in the detection of left atrial thrombi and may be useful in guiding transseptal puncture and in predicting clinical outcomes. Future applications in this ever-expanding field may ultimately include the use of dobutamine stress echocardiography and intravascular ultrasound catheters. It would appear that balloon valvuloplasty and echocardiography are inexorably linked. PMID- 7994746 TI - Percutaneous transvenous mitral commissurotomy using the Inoue balloon: international experience. AB - The Inoue balloon was first used for percutaneous transvenous mitral commissurotomy in 1982 and was commercialized 5 yr later. The experience obtained in thousands of cases performed throughout the world show: (1) the stepwise dilatation technique under echocardiographic guidance appears to be the most efficient and allows the most to be made of this balloon's inherent possibilities, (2) in comparison with other balloon techniques, the advantages of the Inoue balloon are that it is simpler to use, provides equivalent improvement in valve area, and has lower risks, particularly in relation to the production of mitral regurgitation, and (3) long-term results appear similar to those provided by other balloon techniques. Inoue's technique is currently the most widely used for mitral valvuloplasty in the world. Its further development and use depend on further studies of its long-term results together with improvement in the economic aspects. PMID- 7994747 TI - Percutaneous transvenous mitral commissurotomy using Inoue catheter in juvenile rheumatic mitral stenosis. AB - Percutaneous transvenous mitral commissurotomy (PTMC) using Inoue balloon was performed in 270 patients with rheumatic mitral stenosis. Of these 81 (27%), 48 males and 33 females, had juvenile mitral stenosis (age < 20 years, range 9-20 years mean 14 +/- 5). All patients were symptomatic (New York Heart Association [NYHA] class III in 61 patients and class IV in 20 patients). Following PTMC, the mitral valve area (MVA) increased from 0.8 +/- 0.4 to 2.2 +/- 0.5 cm2 (P < 0.001) and the cardiac index increased from 2.4 +/- 0.8 to 3.0 +/- 0.8 L/min/m2 (P < 0.001). Mean transmitral gradients decreased from 24 +/- 8 to 4 +/- 3 mm Hg (P < 0.001). Three (4%) patients had an increase in mitral regurgitation by 1 grade (grade 2/4); however, none required surgery. Significant left to right atrial shunt (Qp/Qs > 1.3: 1) on oximetry was detected in 8 (10%) patients. Overall results were compared to those with adult subgroup of patients with rheumatic mitral stenosis (n = 189, 100 females and 89 males), who underwent PTMC simultaneously. Their age ranged from 21 to 44 years (mean 32 +/- 11 years). The percentage increase in MVA was higher in juvenile as compared to adult patients (172 +/- 61 vs. 154 +/- 69, respectively, P < 0.01). A larger final MVA was achieved in the juvenile group (2.2 +/- 0.5 vs. 1.9 +/- 0.3 cm2, P < 0.05). However, the incidence of increase in mitral regurgitation by 1 grade was similar in two groups (6% vs. 4%, P = NS).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7994748 TI - Characterization of T cell ligands for uromodulin: a possible role in costimulation. AB - In this study, we demonstrate that uromodulin (UMN) is a costimulator of T cells and characterize the T cell ligand which might mediate its costimulatory effect. UMN is an 85-kDa human urinary glycoprotein which is better known for its ability to suppress antigen-induced proliferation of peripheral blood mononuclear cells. It also has a mitogenic effect on peripheral blood cells, which has not been investigated. In this study, costimulation of T cells by UMN is observed only in the absence of B cells and antigen-specific antiserum. Using ligand binding assays we also demonstrate a specific receptor for UMN on peripheral blood T cells and T cell lines (Kd of 10(-8)). We describe two uromodulin binding proteins of approximate M(r) 35 and 55 kDa, isolated from detergent extract of T cells, either of which may represent a receptor for UMN or an associated signal transduction molecule involved in the stimulatory effect of UMN on T cells. Finally, we demonstrate a similar protein in a renal cell line, which may clarify the renal role of UMN. PMID- 7994749 TI - Apolipoprotein E inhibition of proliferation of mitogen-activated T lymphocytes: production of interleukin 2 with reduced biological activity. AB - Apolipoprotein E (apoE), but not apoAI or apoCIII, suppresses mitogen-activated T lymphocyte proliferation, independent of the type of activation signal. Both CD4 and CD8 T cells are inhibited. ApoE inhibits T cell proliferation, in part, by reducing the production of bioactive interleukin 2 (IL2). IL2 activity is reduced by approximately 50-65% in cultures of mitogen-stimulated T cells when apoE is present. ApoE does not significantly alter levels of IL2 mRNA or the mass of secreted IL2 protein, quantitated by enzyme immunoassay. Reduced IL2 activity was not a consequence of induction of IL2 inhibitors in response to apoE or effects of apoE on the bioassay. These results suggest that apoE antagonizes post translational events in mitogen-activated T lymphocytes that are required for the secretion of a bioactive IL2 protein. PMID- 7994750 TI - Selective modulation of IFN-gamma mRNA stability by IL-12/NKSF. AB - We investigated the role of IL-12 in regulating IL-2 and IFN-gamma production in primary culture of human T cells. Addition of neutralizing antiserum against the 40-kDa subunit of IL-12 to PHA-stimulated PBMC markedly reduced both IFN-gamma protein production and mRNA accumulation and stability. Moreover, concurrent treatment of partially purified T cells (> 90% CD3+) with PHA and rIL-12 selectively enhanced IFN-gamma mRNA stability and protein production, while IL-2 protein and mRNA levels were unaffected. These studies also show that IFN-gamma and IL-2 mRNA stability are temporally dissociated during the course of T cell activation, and we propose that this dissociation may be mediated through the production of IL-12. The effect of IL-12 on modulation of IFN-gamma mRNA turnover is not associated with detectable changes in either the levels or affinity of cytoplasmic RNA-binding proteins capable of recognizing AU-rich sequences in the 3'UTR of IFN-gamma mRNA. PMID- 7994751 TI - IL-10 inhibits alloreactive cytotoxic T lymphocyte generation in vivo. AB - In this report, we present evidence that the CTL response directed against MHC Class I allo-determinants can be inhibited as a result of IL-10 expression in vivo. The presence of localized IL-10 secretion at the site of allogeneic tumor cell challenge resulted in marked inhibition of the CTL response and allowed growth of the tumor in the allogeneic host. Using purified CD4+ T cells from mice immunized in the presence or absence of IL-10, we have shown that the loss of alloreactivity as a consequence of IL-10 expression results from the inhibition of CD4+ T cell function. The expression of either IL-2 or IFN-gamma with IL-10 locally at the time of allogeneic cell challenge completely restored CTL alloreactivity, suggesting that the action of IL-10 could be bypassed by providing helper T lymphocyte-derived cytokines of the Th1 type at the site of immunization. Inhibition of alloreactivity by IL-10 was observed using either purified macrophages or dendritic cells as APC in an in vitro assay. Thus, the expression of IL-10 following antigenic challenge (such as that observed in Th2 like immune responses) may profoundly limit the ability for generating functional CTL in vivo. PMID- 7994752 TI - Anti-IgM and anti-IgG modulate c-fos RNA levels differently in human B lymphocytes. AB - One component of the B cell activation cascade is the induction of the protooncogene c-fos. Data presented here demonstrate that stimulation of mIgM bearing cells with either anti-IgM or the combination of PDB plus ionomycin generated comparable levels of c-fos RNA. Furthermore, a synergistic response was observed when the cells were treated with selected concentrations of anti-IgM plus either PDB or ionomycin. In contrast, stimulation of mIgG-bearing B cells with anti-IgG did not induce the c-fos RNA levels that were seen when these cells were treated with the combination of PDB plus ionomycin. Treatment of mIgG bearing cells with only the combination of anti-IgG plus ionomycin yielded a synergistic response and anti-IgG plus PDB did not. Thus, induction of c-fos RNA appears to be different in mIgM- and mIgG-bearing B cells after stimulation through mIg. PMID- 7994753 TI - Relationship between decidual leukocyte infiltration and spontaneous abortion in a murine model of early fetal resorption. AB - The relationship between the early cellular response to embryo implantation and subsequent embryo survival was explored. Immunohistochemistry using the anti CD11b antibody (Mac-1) was used to localize and quantify maternal inflammatory cells present at the fetoplacental interface. CD 11b is expressed mostly on macrophages, but is also present on natural killer (NK) cells, neutrophils, and B cells. The occurrence of CD11b-positive cells at the fetoplacental interface was quantified in CBA/J females mated by DBA/2 males (20-30% embryo loss) and CBA/J females mated by BALB/c males (5-10% embryo loss) in order to investigate the relationship between infiltration by these types of cells and subsequent embryo loss. CD11b-positive cells were found to infiltrate decidua of each embryo starting at Day 6 of gestation. Their numbers sharply increased on Days 7 and 8, to a plateau on Days 8 to 10, well before any damage to the embryo is macroscopically visible on Days 10 to 12 of gestation. The resorption-prone mating of CBA/J female by DBA/2 male showed a significantly elevated number of CD11b-positive cells in 26% of the embryos on the eighth day of gestation compared to CBA/J female by BALB/c male matings which were taken as the reference mating. Moreover, experimental conditions modulating fetal survival in CBA/J mothers such as poly (I:C) treatment of DBA/2-mated females (lower survival) or mating with BALB/c males (higher survival than with the mating with DBA/2 males), were found to be associated with high or low numbers numbers of CD11b-positive cells at the fetoplacental interface. Furthermore, injection of anti-CD 11b into pregnant mice at Day 6 of gestation significantly reduced the subsequent incidence of resorption in the resorption prone CBA/J x DBA/2 mating. These results suggest that CD11b-positive cells are associated with the etiology of spontaneous abortion in this system. PMID- 7994754 TI - Murine strain variation in the natural killer cell and proliferative responses to the immunostimulatory compound 7-allyl-8-oxoguanosine: role of cytokines. AB - 7-Allyl-8-oxoguanosine (loxoribine) is a di-substituted guanine ribonucleoside which has been shown previously to enhance murine NK activity, B lymphocyte proliferation, and antibody synthesis. In this study we examined the relationship among enhancement of NK activity, proliferation, and cytokine synthesis in the responses of different strains of mice to loxoribine to provide insight into the role of cytokines in these biological activities. The NK response of mice was enhanced both in vitro and in vivo in all strains tested with the exception of the NK-deficient beige (BgBg) mouse. However, there was a marked difference in the degree of NK enhancement noted in other inbred strains, with C3H and CBA mice producing the highest responses, C57BL/6, BALB/c, and DBA/2 strains giving intermediate responses, and SJL mice manifesting low responses. Striking enhancement of NK cell activity was seen in SCID mice. A somewhat different effect was seen in humans. Loxoribine treatment enhanced both the NK and LAK activity of cells from individuals with low and high spontaneous NK activity. The degree of enhancement was similar for both groups, and thus the general hierarchy of NK activity among different donors was maintained. There was less interstrain variation in the murine proliferative response to loxoribine although nude (NuNu) mice showed the highest activity and SJL mice produced substantially lower responses than other strains. All strains produced IL-6, TNF alpha, IFN alpha/beta, and IFN-gamma when spleen cells were cultured for 48 hr with loxoribine. Interstrain variability of cytokine synthesis displayed no consistent pattern from one cytokine to another, and all failed to correlate with interstrain variability of NK cell activity or B lymphocyte proliferation. When anti-cytokine antibodies were tested for the ability to block the immunostimulatory effects of loxoribine, only anti-IFN-alpha/beta and, to a lesser degree, anti-IFN-beta, partially inhibited NK activation. Similarly, only anti-IFN alpha/beta antibodies partially blocked the proliferative response to loxoribine. In both cases, reconstitution of the responses was achieved by adding back IFN-alpha/beta to cultures containing antibodies against IFN-alpha/beta. These data suggest that, although several cytokines are produced in response to loxoribine, only IFN-alpha and IFN-beta are directly involved in the NK activation and proliferative responses. The pattern of strain variation appears to be reflective of variation in NK cell responsiveness to IFN-alpha/beta. PMID- 7994755 TI - Cytokines modulate interleukin-6 production by human salivary gland cell line. AB - The ability of HrTNF-alpha, HrIL-1 beta, and HrIFN-gamma to modulate IL-6 production by cultured human salivary cell line (HSG) was examined. IL-6 activity was measured by the hybridoma growth factor biologic activity. HrTNF-alpha had a significant dose-dependent effect, whereas HrIL-1 beta and HrIFN-gamma had moderate and minor effects, respectively. Maximal effect (920 units) was noted when cytokines were applied in combination (1000 units HrIFN-gamma and 20 units HrTNF-alpha) and incubated with human salivary gland cells for 72 hr. The same combination of cytokines had also a marked inhibitory effect (70% of control) on human salivary gland cell growth. This is the first report of these concomitant phenomena in a human cell line originating from salivary tissue. PMID- 7994757 TI - The lack of NK cytotoxicity associated with fresh HUCB may be due to the presence of soluble HLA in the serum. AB - Human bone marrow transplantation is becoming more common in the treatment of certain forms of cancer despite the scarcity of HLA matched donors. Because human umbilical cord blood (HUCB) has been used as a source for stem cells in bone marrow transplantation, and because NK cells appear to be important in graft versus leukemia response, we investigated the lytic activity of freshly isolated HUCB NK cells (HUCB-NK) against tumor targets and their ability to differentiate into LAK cells following stimulation with various cytokines. Although cytotoxicity mediated by fresh HUCB-NK was low compared to that of adult peripheral blood lymphocyte-derived NK cells (PBL-NK), the ability of HUCB-NK to bind to K562 target cells (TC) was similar to PBL-NK. In addition, the PBL-NK cytotoxicity of postpartum mothers was also low compared to that of normal adult PBL-NK. When we incubated HUCB for 18 hr in either IL-2 or IL-12, we boosted the level of HUCB-NK cytotoxicity to approximately the level observed in PBL-NK and increased the level of perforin, granzyme A, and granzyme B mRNA expression. In addition, when we incubated HUCB in IL-2, IL-4, IL-7, IL-12, TNF-alpha, IFN alpha, IFN-gamma, or TGF-beta for 5 days, we observed that HUCB was capable of generating LAK cells only when incubated with either IL-2 or IL-12. In contrast, IL-2, IL-7, IL-12, TNF-alpha, and IFN-gamma all generated LAK cells from adult PBL. When we added to the medium low-dose IL-2 and irradiated K562 as feeder cells (mini-LAK), we were unable to generate LAK activity from HUCB-NK, whereas we could generate it with PBL-NK cells under the same conditions. Addition of serum derived from HUCB in a 4-hr 51Cr release assay with PBL-NK as the effector cells (EC) and K562 as the TC resulted in a 42% decrease in PBL-NK-mediated cytotoxicity. Although we detected no TGF-beta in HUCB serum, we did detect high concentrations of soluble class I MHC (sHLA). To our knowledge, sHLA has not previously been shown to inhibit NK cytotoxicity, although the expression of class I HLA on the surface of TC has been shown to inhibit NK cytotoxicity. To study further the effect of sHLA on cell-mediated cytotoxicity, we added various concentrations of sHLA to EC mediating NK, ADCC, and CTL activities. All were inhibited in a dose-dependent manner.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 7994756 TI - Differential lymphokine expression by rat antigen-specific CD4+ T cell lines with antigen and mitogen. AB - Retinal soluble antigen (S-Ag) and purified protein derivative (PPD)-specific T cell lines established from Lewis rats were used to study the pattern of lymphokine expression to see if it varied with the inducing stimulus. Lymphokine mRNA expression was detected by PCR combined with Southern analysis after 6-hr stimulation and protein secretion assessed by bioassays at 24 hr poststimulation. S-Ag-specific T cell lines when stimulated with antigen expressed IL-2, IFN gamma, and IL-4 mRNA, whereas only IL-2 and IFN-gamma could be detected in the supernatants. This is in contrast to the findings after stimulation of the PPD cell lines with PPD where IL-4 could be detected in the supernatants. The time course studies (3, 6, 24, 48, and 72 hr) with one of the S-Ag-specific T cell lines showed that S-Ag activation did not induce any detectable IL-4 bioactivity. However, when the S-Ag T cell line was stimulated by Con A or PMA, IL-4 was detected in the supernatants following Con A activation, suggesting that the way in which the T cell is activated has an effect on its resultant lymphokine secretion. PMID- 7994758 TI - Interleukin-2 (IL-2) production by human B-cell line. AB - A human B-cell line (Hairy-BM) constitutively secreting interleukin-2 (IL-2) was established from tumor tissue resected surgically from a patient with breast cancer. Hairy-BM was found to be 100% CD20+, 98% surface immunoglobulin (sIg) G+, 98% sIg kappa chain+, 100% HLA-DR+, 94% IL-2 receptor (IL-2R alpha), 98% IL-2R beta, and devoid of T-cell, monocyte, and natural killer cell surface antigens. The B-cell origin of Hairy-BM was also confirmed by clonally rearranged Ig heavy- and Ig light-chain genes. The growth of Hairy-BM expressing IL-2R was promoted by recombinant IL-2 (rIL-2) and anti-CD25 antibody significantly blocked the growth enhancement. IL-2 secretion from Hairy-BM was confirmed by radioimmunoassay. By using a sensitive polymerase chain reaction technique, we demonstrated that Hairy BM expressed IL-2 mRNA, IL-2R alpha mRNA, and IL-2R beta mRNA. These findings indicate that certain B-cells not only produce, but also respond to IL-2 in an autocrine fashion with increased proliferation. PMID- 7994759 TI - Suppression of HIV replication by CD8+ cell clones derived from HIV-infected and uninfected individuals. AB - CD8+ cell clones have been derived from peripheral blood mononuclear cells of human immunodeficiency virus (HIV)-infected and uninfected individuals. Several of these cloned cells have the ability to suppress HIV replication when cocultured with CD4+ cells acutely infected in the laboratory with HIV or with infected CD4+ cells from infected subjects. Suppression of virus production occurs without killing the target cells. With the CD8+ cell clones studied, this antiviral response correlated with production of a filterable factor that has antiviral activity. These cell clones offer the opportunity for identification of the factor mediating suppression of HIV replication. Moreover, adoptive transfer of cell clones might provide a valuable therapeutic approach for HIV-infected individuals. PMID- 7994760 TI - Apoptotic cell death induced by anti-IgM antibody and phorbol esters is inhibited by interleukin-4 in human B lymphoma cell line MBC-1. AB - The development of B cell tolerance is believed to involve negative signaling to B cells derived from the binding of antigen to the B cell surface immunoglobulin. B cell lines that receive negative signals may provide useful models for studying the mechanisms of B cell tolerance. We have established a human B lymphoma cell line, MBC-1, positive for both surface IgM and IgD. The growth of MBC-1 cells is inhibited by anti-IgM antibody but not by anti-IgD antibody. The rapid time course of MBC-1 cell death, the morphologic feature of dying cells, and DNA fragmentation indicate that surface IgM cross-linking induces apoptotic cell death. Interestingly, interleukin-4 (IL-4) could rescue MBC-1 cells from this apoptotic signal. BCL-2 protein is neither expressed nor induced in MBC-1 cells. The treatment of MBC-1 cells with IL-4 does not interfere with mobilization of Ca2+ or induce any phenotypical change. In addition, phorbol 12-myristate 13 acetate and phorbol 12, 13-dibutyrate also induced growth inhibition followed by apoptotic cell death in MBC-1 cells. IL-4 is able to protect MBC-1 cells from cell death, but not from growth inhibition induced by protein kinase C activators. The results collectively suggest that IL-4 could inhibit the transduction of apoptotic signal following the activation of protein kinase C in MBC-1 cells. PMID- 7994761 TI - Inhibition of protein tyrosine phosphorylation prevents T-cell-mediated cytotoxicity. AB - Several lines of evidence point to a central role for protein tyrosine kinases (PTKs) in the signal transduction cascade initiated by T-cell receptor (TCR) engagement. In cytotoxic T lymphocytes (CTL), TCR crosslinking leads to activation of the lytic process which includes conjugate formation, lethal hit delivery, and events leading to target cell death. We studied the role of PTKs in antigen-specific cytotoxicity exerted by both in vivo activated and in vitro maintained CTL. We found that the PTK inhibitors herbimycin A and genistein blocked T-cell-mediated lysis in a dose-dependent manner. Lack of cytotoxic function was not due to abrogation of conjugate formation, but was associated with inhibition of both granule exocytosis and phosphatidylinositides turnover, thus indicating that PTK activity is an obligatory event for the activation of antigen-specific CTL effector function. PMID- 7994762 TI - Infiltration of CD4+ T cells into cornea during development of Onchocerca volvulus-induced experimental sclerosing keratitis in mice. AB - Sclerosing keratitis is the major cause of blindness due to onchocerciasis caused by the parasite Onchocerca volvulus. Although the importance of T cells in the pathogenesis of onchocerciasis has been suggested, their precise role in onchocercal sclerosing keratitis has not yet been defined. Using immunohistological techniques and a murine model of onchocercal sclerosing keratitis, we have performed a temporal analysis of the inflammatory T cells infiltrating into the cornea at Days 4, 7, and 21 following intrastromal challenge with soluble O. volvulus antigens into presensitized mice. The maximum number of CD3+ T cells were observed in the corneal stroma at Day 21 when sclerosing keratitis was most severe. The majority (> 85%) of the CD3+ T cells were CD4+ at all time points. A few infiltrating cells bore IL-2 receptors indicating possible activation of a small fraction of the T cells. These results suggest that CD4+ T cells play an important role in onchocercal sclerosing keratitis. PMID- 7994763 TI - Noninvolvement of V beta 8+ T cells in murine thyroglobulin-induced experimental autoimmune thyroiditis. AB - In experimental autoimmune thyroiditis (EAT) induced with mouse thyroglobulin (MTg), T cell receptor (TCR) V beta gene usage in the pathogenesis of disease is unknown. We report here studies evaluating V beta 8 gene usage in EAT, as V beta 8+ T cells are reportedly involved in some experimental autoimmune diseases. Spleen cells (SC) from MTg-immunized CBA/J (H-2k) mice were activated in vitro for adoptive transfer into syngeneic recipients. Elimination of V beta 8+ T cells by treating recipients with V beta 8 monoclonal antibody (mAb) following transfer of MTg-activated SC did not reduce disease severity. Conversely. MTg-primed SC were stimulated in vitro with V beta 8 mAb or staphylococcal enterotoxin B, which activates V beta 8+ T cells in CBA/J mice. Neither activated population transferred disease, in contrast to cells activated with MTg. Thus, in MTg induced EAT, V beta 8+ T cells do not play a major role in pathogenesis. PMID- 7994764 TI - Macrophage response to viruses, protozoa, and fungi: secretory and cellular activities induced in resting unprimed bone marrow-derived mononuclear phagocytes. AB - The secretory (tumor necrosis factor, TNF-alpha; nitrite) and cellular response (mitochondrial respiration, TNF-alpha-independent tumoricidal activity) of a pure, lymphocyte-free population of resting, unprimed rat bone marrow-derived mononuclear phagocytes (BMM phi) to direct interaction with viruses, protozoa, and fungi was assessed and compared with that triggered by bacterial agents and interferon-gamma (IFN-gamma). Viruses (herpes simplex, vaccinia, poliomyelitis, vesicular stomatitis, lymphocytic choriomeningitis, Sendai), protozoa (Trypanosoma brucei, Giardia lamblia), and fungi (Penicillium, Trichosporon, Fusarium, Rhizopus, Aspergillus, Geotrichum species) affected primarily the secretion of TNF-alpha and mitochondrial respiration of BMM phi; their effects on the secretion of nitrite and on tumoricidal activity were at best marginal. Collectively, the macrophage response to viruses, protozoa, and fungi was less varied and less marked than that to bacterial agents (intact organisms, peptidoglycan, lipoteichoic acid, lipopolysaccharide) and IFN-gamma. PMID- 7994765 TI - Transferrin receptor expression as a marker of immature cycling thymocytes in the mouse. AB - Dividing cells require iron and, therefore, express the transferrin receptor (CD71) on the cell surface to enable internalization of transferrin-bound iron. Since early T cell development is marked by intense proliferation, we questioned whether CD71 might serve as a marker of immature T cells. Therefore, we analyzed the expression of CD71 on fetal, neonatal, and adult thymocytes in correlation with cell size, cell cycle status, and expression of CD3, CD4, CD8, alpha beta TcR, and gamma delta TcR. Phenotypic analysis showed that only the large, immature CD4-8-3-, CD4-8+3-, and CD4+8+3- cells in fetal, neonatal, and adult thymus expressed CD71. In addition, DNA analysis showed that all CD71+ large adult thymocytes were cycling. Downregulation of CD71 occurs when proliferation ceases, i.e., within the CD4+8+3- thymocyte subpopulation. The gradual changes in size and CD71 expression suggest a sequential development within this CD4+8+3- subpopulation from large CD71+ via small CD71+/- to small CD71- cells. As a consequence, CD71 expression is downregulated, in adult T cell development as well as in ontogeny, before the alpha beta TcR appears on the cell surface of the thymocyte. Together, our findings show that CD71 is a marker of immature, proliferating T cells. PMID- 7994766 TI - [Effect of pentoxifylline on respiratory distress syndrome in dogs]. AB - We examined effects of early post-treatment with pentoxifylline (PTX) on fat tissue extract (FTE) induced respiratory distress syndrome in dogs. The results indicate that the arterial oxygen tension in the animals received PTX dropped more slowly, the total leukocytes and albumin in BALF were obviously reduced, the increased production of IL-1 and TNF by alveolar macrophages was partly inhibited, other parameters such as W/D ratio were also markedly decreased when compared to the animals received FTE only. PTX decreases neutrophil accumulation and prevents the increase in pulmonary vascular permeability, and attenuates edema formation in FTE-induced lung injury. The mechanism may relate with the effect of PTX inhibiting inflammatory leukocytes and protecting the pulmonary vascular endothelial cells. PMID- 7994767 TI - [The role of pentoxifylline in acute lung injury complicated by pancreatitis]. AB - Caerulein-induced acute pancreatitis in rats commonly complicated ARDS-like acute lung injury. Acute pancreatitis induced by caerulein in the circulating neutrophil-depleted rat by hydroxyrea or with the administration of SOD, CAT or Pentoxifylline, the wet lung weight, lung capillary endothelial permeability decrease significantly compared to the caerulein group (P < 0.05). There are no lung morphologic evidences of neutrophil sequestration, interstial edema, intralveolar hemorrhage that seen in caerulein infusion animals. But it has no effect against the development of acute pancreatitis. It suggested that neutrophil and neutrophil-derived oxygen radical are the important mediators of acute lung injury complicated by pancreatitis. PMID- 7994768 TI - [Indication for emergency pulmonary resection in patients with massive hemoptysis]. AB - Emergency pulmonary resection was done in 24 patients with massive hemoptysis from January 1983 to December 1992. The curative, morbidity and mortality rates were 95.8%, 16.6% and zero respectively. Above mentioned result was better than that of the author's report in 1986. It was shown that emergency lung resection should be active when the drug therapy failed, the site of hemoptysis was clear, the lung lesion was localized and the general condition and cardiopulmonary function was good, especially the cases had a history of suffocation, hypotension or shock. In spite of the present result of emergency lung resection for massive hemoptysis tends to be better, the operative complication is still higher than routine pulmonary resection. Therefore, the operative indication should be strictly handled. For cases whose surgical indication is inadequate, bronchial arterial embolization is an effective and relative safe method. PMID- 7994769 TI - [In situ PCR-gene hybridization method for detecting mycobacterium tuberculosis in tissue specimens]. AB - The authors combined the technique of polymerase chain reaction (PCR) with hybridization in situ, and find the method is better, quicker and more sensitive for detecting a trace of bacterial DNA, especially for observing the relation between the lesion and the peripheral tissue, the method is more simple and no radioactive pollution. It seems to be suitable for detection on samples from autopsy, biopsy and smears. We suppose the method might have a prospect for clinical diagnosis. PMID- 7994770 TI - [The clinical significance of detection of anti-PPD-IgG secreting cell, adenosine deaminase and anti-PPD-IgG antibody in pleural effusion]. AB - Enzyme-Linked Immunospot Assay (ELISPOT) were designed in the diagnostic value of tuberculous pleurisy, had a sensitivity of 90% and specificity of 100%. Anti-PPD IgG antibodies detected by ELISA had a sensitivity of 45% and specificity of 86%. For ADA activity in pleural effesion, the sensitivity and specificity were 75%, 79% respectively. Comparing with ADA and ELISA methods, ELISPOT is a more useful method for diagnosis of tuberculosis pleurisy. PMID- 7994771 TI - [Detection and clinical significance of PPD-IgG antibody in cerebrospinal fluid by ABC-ELISA method]. AB - PPD-IgG antibody in cerebrospinal fluid (CSF) of 55 patients with tuberculous meningitis (TBM) and 37 patients with non-TBM was determined by ABC-ELISA method, and compared with ELISA. The positive rate of ABC-ELISA and ELISA was 96.4% and 83.6% respectively (P < 0.05). Specificity of two methods was 97.3%. Meanwhile the positive rate in CSF (96.4%) is markedly higher than that in sera (85.5%) (P < 0.05). The results showed that this method can be as a supporting method for diagnosis of TBM. PMID- 7994772 TI - [The suggestive indication for operation on pulmonary tuberculoma--based on the bacteriologic study on the tuberculous section samples]. AB - The pathologic features, tuberculous bacilli and antituberculous drug resistance were studied on lung section samples from 16 patients with pulmonary tuberculoma. The authors found that in about half of the samples the tuberculous bacilli were positive. When the diameter of the lesion was > 3cm, the positive rate for bacilli was high and the isolated bacilli were resistant to different antituberculous drugs in various level. The indication for operation was also recommended. PMID- 7994773 TI - [Hamartoma of the lung: an analysis of 24 cases]. AB - Hamartoma is one of the most common benign tumors in the lung, and most of the lung hamartomas are located in the parenchyma. This report reviews 24 cases with this kind of tumor. The male-female ratio was 1.4:1 and the mean age 46.4 years. Sixteen patients of the 24 were asymptomatic, while in the remainder cases chest pain or distress, cough, short breath or hemoptysis were presented. Lung hamartoma is usually composed of cartilage, fat, smooth muscle and respiratory epithelium. X-ray findings of the parenchymal type in these cases were characterized by a round or oval sharply outlined mass, but only one with a mass in the shape of a dumbbell. 33% cases showed calcification. In 19 cases the mass was < 3.0 cm diameter (79%) and in 17 it was located in the superficial edge of the lung. The diagnosis was confirmed in only 6 cases preoperatively. The other cases were misdiagnosed as lung cancer, tuberculoma, metastatic tumors of the lung, etc. Enucleation or wedge resection is desirable for this kind of tumor. PMID- 7994774 TI - [Roentgenological and pathological findings in 22 cases of secondary fungus ball of pulmonary aspergillosis]. AB - Twenty-two cases of secondary fungus ball of pulmonary aspergillosis defined by operation were reported. All cases were referred with incorrectly diagnosis to the authors and only 45.3% were correctly diagnosed before operation. The roentgenological and pathological findings were studied. The results show that not familiar with non-typical appearance is the most common cause for incorrect diagnosis. PMID- 7994775 TI - [Relative DNA content and cycle distribution of cells in pleural effusions studied by flow-cytometry]. AB - Pleural effusions from 28 patients were studied by cytology, chromosome and flow cytometry. Relative cellular DNA content was measured. An estimate of ploidy as well as cycle distribution has been given. Eighteen patients suffered from malignant effusions while the rest had TB effusions. 83.3% of malignant effusion had aneuploid. The relative cellular DNA content and the cell cycle distribution can provide valuable and decisive information. The study of chromosome also help the diagnosis in addition to cytological results. PMID- 7994776 TI - [An evaluation of fibronectin and IgG in bronchoalveolar lavage fluid of patients with interstitial lung diseases]. AB - FN and IgG levels in both bronchoalveolar lavage fluid and peripheral blood were evaluated in 25 patients with ILD and in 11 normal controls. The results showed: (1) In normal group, the level of lavage fluid FN was similar to that of plasma (P > 0.05). FN levels in BALF of patients with ILD were not only significantly higher than those of controls, but also than those of their own plasma (P < 0.01). However, plasma FN levels showed no remarkable changes in all study groups. (2) IgG levels were significantly increased in BALF of patients with ILD and were somewhat elevated in serum. (3) There were significant correlations between lavage FN or IgG levels and total cell counts in ILD, lavage FN and percentage of neutrophils in IPF, and lavage FN or IgG and percentage of lymphocytes in non-IPF. (4) A highly significant correlation existed between FN and IgG levels in BALF of patients with ILD. These data suggested that FN is significantly increased in patients with ILD. Elevation of lavage FN in ILD may be served as a marker of activity in assessment of alveolitis and elevation of lavage IgG appears to reflect an aspect of activity of humoral immunologic reaction in patients with ILD. PMID- 7994777 TI - [215 cases of diffuse pulmonary disease diagnosed with transbronchial lung biopsy via bronchofibroscope]. AB - 215 cases of diffuse pulmonary disease diagnosed with transbronchial lung biopsy (TBLB) via bronchofibroscope were reported. The incidence of successful biopsy was 96.7%. The total diagnostic rate was 80.5%. There were no other serious complications except for bloody or blood-streaking sputum, but the amount rarely exceeded 50 ml, and pneumothorax occurred occasionally. It was suggested that TBLB is an easy, safe and useful method for diagnosing diffuse pulmonary disease. PMID- 7994778 TI - [Effects of L-arginine on pulmonary circulation and cerebral blood flow in acute and chronic hypoxic rats]. AB - The effects of L-arginine (L-Arg) on pulmonary circulation and cerebral blood flow in acute and chronic hypoxic rats and their mechanism were studied. The results showed that bolus injection of L-Arg 400mg.kg-1 did not inhibit acute hypoxic pulmonary vasoconstriction (HPV), while 800mg.kg-1 could inhibit HPV. Neither of these two doses of L-Arg was found to have any influence on the change in cerebral blood flow during acute hypoxia. Long-term administration of L-Arg (300mg.kg-1/d) could attenuate chronic hypoxic pulmonary hypertension, the increase in pulmonary vascular resistance and right ventricular hypertrophy, and the HPV as well. It did not influence the cerebral blood flow. Since the inhibitor of NO synthetase, NG-nitro-L-arginine methyl ester, could antagonize the effect of L-Arg, it is suggested that an increase in the synthesis of NO might contribute to the effect of L-Arg. PMID- 7994779 TI - 5th International Conference on Treatment of Urinary Tract Tumors with Adriamycin/Farmorubicin. Hakone, Japan, 24-25 September 1993. PMID- 7994780 TI - Superficial bladder cancer: state of the art. PMID- 7994781 TI - Results of adjuvant chemotherapy for invasive urothelial cancer with lymph-node metastasis. AB - From 1980 to 1991, 59 patients with advanced urothelial cancer (pathological stage, > pT3) underwent radical operations. Of these 59 patients, 33 had nodal involvement. This study focused on those 33 patients with nodal involvement. The primary site was the urinary bladder in 20 patients and the upper urinary tract (renal pelvis and/or ureter) in 13. In all, 13 patients underwent adjuvant chemotherapy with an M-VAC or M-VEC [methotrexate (M), vinblastine, doxorubicin (ADM) or epirubicin, and cisplatin (CDDP)] regimen, and another 8 patients were treated with other insufficient chemotherapies [CDDP + ADM or CDDP + ADM + etoposide (VP-16)]. A group of 12 patients did not receive any additional treatment. Most of the patients in the M-VAC and M-VEC groups received more than 2 cycles of the regimen (median, 3.2 cycles; range, 1-9 cycles). The overall 5 year survival rate of the M-VAC and M-VEC group was 31%, whereas the rate was 0 for the other insufficient-chemotherapy groups and the no-chemotherapy group. Of the 13 patients in the M-VAC group, 4 (31%) patients were alive without disease progression and 9 (69%) were dead due to progressive disease. In the other groups, only 1 patient was alive without progression. Our results suggest that adjuvant M-VAC or M-VEC chemotherapy may extend the median survival of patients with advanced urothelial cancer, but it failed to reduce the rate of cancer death. PMID- 7994782 TI - Chemo-endocrine therapy for prostate cancer with bone metastasis. Nagasaki Prostate Cancer Research Group. AB - We analyzed the clinical effects of initial chemoendocrine therapy on 31 prostate cancer patients with bone metastasis. These patients had been newly diagnosed between 1983 and 1991 and had received no previous therapy. As endocrine therapy, the patients received 1 mg ethynylestradiol daily with or without orchiectomy. In addition, they received three courses of chemotherapy consisting of 20 mg/m2 cisplatin given on days 1, 3, and 5 and 20 mg/m2 Adriamycin or 40 mg/m2 epirubicin given on day 5. Subsequently, for maintenance therapy, the patients received 1 mg ethynylestradiol and 150 mg 5-fluorouracil [or 300 mg tegafur plus uracil (UFT)] daily. Patients given our regimen of chemoendocrine therapy had a significantly better prognosis than did the controls treated with endocrine therapy alone (P = 0.05), although treatment was not randomized. The cause specific survival rates at 5 years for the chemoendocrine-therapy patients and the control group were 65.4% and 37.4%, respectively. A multivariate analysis of possible prognostic factors, i.e., age, histological grade, prostatic acid phosphatase, tumor-related pain, the extent of disease (EOD) on bone scan, and the type of initial treatment, confirmed that the initial treatment (P = 0.03) and the EOD grade (P = 0.05) had a significant effect on survival. On the basis of these results, it is necessary to carry out a randomized trial to compare our chemoendocrine regimen with endocrine therapy alone in untreated patients with advanced prostate cancer. PMID- 7994783 TI - A randomized trial of early intravesical instillation of epirubicin in superficial bladder cancer. The Nagoya University Urological Oncology Group. AB - A total of 135 patients with superficial bladder cancer diagnosed as totally resectable were entered into a randomized multicenter trial to investigate the efficacy of early intravesical epirubicin instillation after resection in comparison with transurethral resection (TUR) alone. Epirubicin (40 mg/40 ml saline) was given within 24 h of TUR and once during the 1st week, weekly for 4 weeks and then monthly for 11 months. In all, 122 patients (90.4%) were eligible and 119 (88.1%) were evaluable. The interval to initial recurrence was significantly longer (P = 0.02) in the epirubicin group (36 months; 95% confidence interval, 32-40 months) than in the group receiving TUR alone (28 months; 95% confidence interval, 24-32 months). The recurrence rate per year in the epirubicin group was less than that in the TUR-alone group (0.13 versus 0.29 annual recurrences). Disease progression was observed in only one patient in the epirubicin-instillation group. The main toxicity encountered was bladder irritation (13.8%). These results demonstrate that early intravesical epirubicin instillation is efficacious in preventing local recurrence. PMID- 7994784 TI - Prospective randomized study of prophylaxis of superficial bladder cancer with epirubicin: the role of a central pathology laboratory. Nara Uro-oncology Research Group. (NUORG). AB - The preliminary results of a multi-institutional prospective randomized study of the prophylaxis of superficial bladder cancer using epirubicin (protocol NUORG SBT-003) are reported. The subjects were 129 patients with untreated superficial bladder cancer (< or = T1b, < or = G2) who were randomized into 2 groups: a transurethral resection (TUR)-alone group (63 patients) and a TUR + intravesical epirubicin (20 mg/40 ml, 30 times/2 years) group (66 patients). The nonrecurrence rate observed in the epirubicin group was significantly higher than that seen in the control group. To unify the pathological diagnosis, a central pathology laboratory (CPL) was set up for extramural review. The correspondence of the pathological diagnosis of TUR-Bt specimens between the CPL and the local pathology laboratory (LPL) was 70.5% in grading and 51.9% in staging. There was a tendency for overdiagnosis by the LPL for both the grade and the stage of tumors. However, differing interpretations by pathologists seem to exert little influence on the nonrecurrence rate at interim analysis. Further observation will be necessary to clarify the prophylactic efficacy of low-dose, long-term periodic intravesical epirubicin instillation and the influence of the disagreement in pathological findings between the CPL and the LPL on the analysis of the results. PMID- 7994785 TI - Prophylactic chemotherapy with anthracyclines (adriamycin, epirubicin, and pirarubicin) for primary superficial bladder cancer. The Hokkaido University Bladder Cancer Collaborative Group. AB - A multicentric randomized trial was conducted to evaluate the efficacy of intravesical chemoprophylaxis for primary superficial bladder cancer. The 299 eligible patients with primary superficial bladder cancer were randomized into four groups (A, B, C, and D) after pathological confirmation. Intravesical instillation of drugs, which were dissolved in 20 ml physiological saline (PS; group A, 20 mg Adriamycin; group B, 20 mg epirubicin; group C, 20 mg pirarubicin; group D (control), PS alone], was performed once a week for 2 weeks after trasurethral resection and then once every 2 weeks for 14 weeks, once monthly for 8 months, and once every 3 months for 1 year. No significant difference in the patients' characteristics was found among the four groups. The follow-up period ranged from 3 to 31 months (mean, 14 months). The nonrecurrence rates were estimated by the method of Kaplan and Meier. The relative effects of five variables (the tumor status, size, grade, and stage and the treatment) on the efficacy of the chemoprophylaxis regimens were evaluated using a multiple regression model. Although the nonrecurrence rates determined for groups A and B were significantly higher than that found for group D (P < 0.05), no significant difference in the nonrecurrence rate was detected among groups A, B, and C. The multiple regression model indicated that the most important factors in preventing tumor recurrence at 12 or 24 months were the intravesical instillation of an anthracycline and the tumor status (solitary). These results demonstrate that intravesical instillation of the tested anthracyclines is effective for at least 2 years as prophylactic chemotherapy for primary superficial bladder cancer. PMID- 7994786 TI - Comparison of the prophylactic usefulness of epirubicin and doxorubicin in the treatment of superficial bladder cancer by intravesical instillation: a multicenter randomized trial. Kobe University Urological Oncology Group. AB - A multicentric randomized trial was conducted for the purpose of investigating the prophylactic efficacy of intravesical epirubicin instillation following transurethral resection of superficial bladder cancer in comparison with the efficacy of doxorubicin. The patients were centrally randomized into 2 groups and received 19 intravesical instillations of epirubicin or doxorubicin at 30 mg/30 ml physiological saline twice a week for 4 weeks and then once monthly for 11 months. A total of 150 patients with Ta and T1 superficial bladder cancer were entered in the trial, and 114 were evaluable. The nonrecurrence rates determined for each group at 1 and 2 years by the Kaplan-Meier method were 92.8% and 88.6%, respectively, for the epirubicin group and 86.4% and 81.7%, respectively, for the doxorubicin group. The differences between the two groups were not statistically significant. The main side effects encountered in this study were symptoms of bladder irritation such as micturitional pain, pollakisuria, and hematuria. The respective frequencies of those symptoms were 10%, 15.0%, and 5.0% in the epirubicin group and 14.8%, 14.8%, and 0 in the doxorubicin group. These results suggest that epirubicin is a useful drug, comparable with doxorubicin, for intravesical instillation chemotherapy in the prophylactic treatment of superficial bladder cancer. PMID- 7994787 TI - A phase II study of prophylactic intravesical chemotherapy with 4'-epirubicin in recurrent superficial bladder cancer: comparison of 4'-epirubicin and adriamycin. AB - Since intravesical recurrence of superficial bladder cancer (Ta, T1) after transurethral resection (TUR) is frequent, adjuvant therapy to reduce the recurrence rate has been extensively investigated. Although intravesical chemotherapy has been employed for 30 years or more, neither the exact effect on the bladder epithelium nor the optimal dose and administration schedule has yet been clarified. In recent years, several derivatives of Adriamycin (ADR) have been developed, and 4'-epirubicin (FARM) is one of them. This drug has been shown to have antitumor effects almost equal to those of ADR and to produce less toxicity when given systemically as chemotherapy. In an attempt to clarify the effect of intravesical FARM in the prevention of recurrence of superficial bladder cancer, we conducted a prospective randomized trial to compare the effects of equal doses of FARM and ADR given by intravesical instillation after TUR in cases of highly recurrent superficial bladder cancer. A total of 73 patients with recurrent superficial bladder cancer were randomized to receive TUR and either 30 mg FARM or 30 mg ADR by intravesical instillation every 2-4 weeks for 1 year. The prophylactic effect on recurrence and the toxic effects of these drugs were investigated. The current results show that FARM provides efficacy almost equal to that of ADR in the prevention of recurrence in these patients. However, FARM also caused almost the same local toxic effects (bladder irritation, among others) as ADR. On the basis of these preliminary results, FARM is surmised to be one of the agents as beneficial as ADR in the prevention of recurrence of superficial bladder cancer. PMID- 7994788 TI - Phase II study of intravesical chemoprophylaxis of epirubicin after transurethral resection of bladder tumors. Tottori University Oncology Group. AB - We performed intravesical instillation of epirubicin in 53 patients with the aim of preventing recurrence of bladder tumors. The patients had undergone transurethral resection of superficial bladder tumors (only transitional-cell carcinoma) within the preceding week, between January of 1990 and July of 1991. Recurrence was found in 11.3% (6/53) of cases during follow-up periods lasting from 1 to 20 months. Side effects occurred in 5.7% (3/53) of the patients. The cumulative nonrecurrence rate was 96.0% for a follow-up period of 6 months and 78.4% for 12 months. The results of this study suggest that intravesical instillation of epirubicin is very useful as adjuvant therapy after transurethral resection of superficial bladder tumors. PMID- 7994789 TI - A phase II study of prophylactic intravesical chemotherapy with epirubicin in the treatment of superficial bladder cancer. Tokyo Women's Medical College Bladder Cancer Collaborating Group. AB - Intravesical instillation of epirubicin was carried out to investigate the efficacy of this treatment in preventing postoperative recurrence of superficial bladder cancer. The subjects were 100 patients who had been treated with transurethral resection (TUR) for superficial transitional-cell carcinoma of the bladder (classified as primary or recurrent superficial bladder cancer of pathological stage Tis, Ta, or T1 and histological grade G1, G2, or G3) at Tokyo Women's Medical College Hospital and its affiliated hospitals during the 2-year period ranging from April of 1990 through March of 1992. A solution of epirubicin was prepared by dissolving 20 mg in 30 ml physiological saline, and this was instilled into the bladder a total of 17 times during 1 year: once immediately after TUR, once every 2 weeks for the next 4 months, and then once per month for the following 8 months. Thereafter, the course of each patient was followed by performing urinary cytodiagnosis once each month and cystoscopy once every 3 months. Of the 100 patients, 83 were evaluable. The mean duration of follow-up was 461 +/- 222 days, and the recurrence rate was 30.1% (25/83 cases). The recurrence rate determined for primary cases was 19.7%, whereas that recorded for recurrent cases was 61.9%. Adverse effects occurred in 9.3% (9/97) of the patients, but these side effects were mild in severity and the instillation regimen did not have to be discontinued in any of the patients. Analysis of the risk factors for recurrence revealed significantly higher recurrence in the recurrent-patient group and the multiple-tumor group. On the basis of these findings, the authors surmised that when given in an intravesical instillation regimen, epirubicin causes few adverse effects, and its efficacy in the prophylaxis of recurrence of superficial bladder cancer is equivalent to that thus for reported for other drugs. At present, the authors are carrying out a controlled clinical study on epirubicin that takes into account the risk factors for recurrence of superficial bladder cancer. PMID- 7994790 TI - The effects of intravesical chemoimmunotherapy with epirubicin and bacillus Calmette-Guerin for prophylaxis of recurrence of superficial bladder cancer: a preliminary report. AB - The effects of intravesical chemoimmunotherapy with epirubicin and bacillus Calmette-Guerin (BCG) for prophylaxis of recurrence of superficial bladder cancer (pTa, pT1) were investigated in 29 patients aged a median of 70 years between January of 1991 and May of 1993. The patients received intravesical instillation of 40 mg epirubicin immediately after transurethral resection (TUR) of the bladder cancer. At 1 week after TUR, 80 mg Tokyo-strain BCG was instilled into the bladder once a week for 6 weeks. Thereafter, the patients were followed by cystoscopy and urinary cytology at 3-month intervals until recurrence was detected. Of the 29 patients, 28 had no evidence of disease over a mean follow-up period of 20 months. The 1 case of recurrence occurred at 3 months after TUR and that patient died of cancer progression. The simple recurrence rate was 3.5% after therapy. According to the person-years method, the number of recurrent tumors per 100 patient-months was 0.17. The cumulative nonrecurrence rate determined for all cases was 96.5% at 30 months. Adverse reactions, including urinary frequency, urgency, and miction pain, among others, were observed in 27 patients (93%). Only 1 patient was withdrawn from the treatment because of severe bladder-irritation symptoms due to the BCG instillation. The intravesical chemoimmunotherapy with epirubicin and BCG seemed to be effective for prophylaxis of recurrence of superficial bladder cancer. PMID- 7994791 TI - Intravesical instillation chemotherapy of adriamycin with or without verapamil for the treatment of superficial bladder cancer: the final results of a collaborative randomized trial. AB - A collaborative randomized clinical trial on the intravesical administration of Adriamycin (ADM) with or without verapamil (VR), a calcium-channel blocker, as chemotherapy of superficial bladder cancer (Ta, T1) was carried out at two universities, Okayama and Kagoshima, and their affiliated hospitals. Arm A consisted of ADM given at 50 mg/50 ml saline, and arm B consisted of ADM given at 50 mg/40 ml saline plus five ampules (25 mg/10 ml saline) of injectable VR. The drugs were instilled into the bladder for 3 consecutive days, and three such courses were given with a 4-day interval between each course for a total of nine instillations. A total of 96 patients (48 in arm A and 48 in arm B) were entered into this study. The two treatment groups showed no significant difference in background factors. Of the 40 evaluated arm-A patients, 24 (60.0%) showed a response (CR + PR), whereas 19 (48.7%) of the 39 patients in arm B responded. The difference between these response rates was not statistically significant. As for adverse reactions to the intravesical chemotherapy, local inflammatory symptoms were observed in half of the patients, although no systemic reaction was observed. No significant difference was found between arm A and arm B, except for urinary turbidity. In conclusion, at the dose employed in the present clinical trial, there was no clear enhancement of the effect of ADM combined with VR in patients with superficial bladder cancer. Further clinical studies are required to determine the optimal doses of ADM and VR for their combination in intravesical chemotherapy. PMID- 7994792 TI - Prophylactic intravesical chemotherapy with adriamycin plus verapamil for primary superficial bladder cancer: preliminary results. The Kyushu University Urological Oncology Group. AB - A prospective randomized trial was conducted to compare the prophylactic effect of intravesical installation of Adriamycin (ADM) plus verapamil (VR) with that of ADM alone for recurrence of superficial bladder cancer. A total of 226 patients were enrolled and randomized into 2 groups. Group A received intravesical instillation of ADM (30 mg/30 ml physiological saline) on 19 occasions during a 1 year period after transurethral resection, whereas group B received intravesical instillation of ADM (30 mg/24 ml physiological saline) plus VR (15 mg/6 ml saline) according to the same schedule used for group A. Evaluation was possible in 157 of the 226 registered patients (group A, 76; group B, 81). There was no significant difference in the patients' characteristics between the two groups, and there was no significant difference in the overall nonrecurrence rate determined over a 24-month follow-up period. However, group B showed a significantly higher nonrecurrence rate than did group A for tumors measuring less than 1 cm in diameter (P < 0.05) and for histological grade 2 tumors (P < 0.01) in spite of there being no significant difference in the other characteristics of each subgroup of patients. The incidence and severity of side effects were similar in both groups, and VR caused no significant systemic toxicity. Although further follow-up is necessary, these results suggest that intravesical instillation of ADM plus VR is clinically safe and may be more effective than instillation of ADM alone in preventing the postoperative recurrence of superficial bladder cancer (less than 1 cm in diameter, histological grade 2). PMID- 7994793 TI - Single instillation of hydroxypropylcellulose-doxorubicin as treatment for superficial bladder carcinoma. AB - A single instillation of hydroxypropylcellulose (HPC)-doxorubicin (20 mg/20 ml) was performed in 20 patients with superficial bladder carcinoma. The therapeutic effect was assessed by cystoscopy at 14-30 days after the instillation, and the residual tumor tissue was resected by transurethral resection (TUR) when possible. The results obtained for the therapeutic effect were as follows: a complete response (CR), in 7 cases (35%); a reduction in size of more than 50% (partial response, PR), in 6 cases (30%); and a reduction of less than 25% in size (no change, NC), in 7 cases (35%). Combined intravesical instillation of HPC doxorubicin and local hyperthermia using a Thermotron RF-8 was performed in 11 patients with recurrent superficial bladder carcinoma. The total number of treatment courses ranged from three to five per patient. The results obtained for the effect of this combined treatment were as follows: a CR, in 6 cases (54.5%); a PR, in 3 cases (27.3%); and NC, in 2 cases (18.2%). Therefore, the combination of intravesical instillation of HPC-doxorubicin and local hyperthermia was more effective against superficial bladder carcinoma than the single instillation of the chemotherapeutic agent alone. PMID- 7994794 TI - Studies of effects of anticancer agents in combination with/without hyperthermia on metastasized human bladder cancer cells in chick embryos using the polymerase chain reaction technique. AB - Cultivated T24 cells derived from a human bladder cancer were inoculated into the chorioallantoic membrane vein of chick embryos. Hyperthermic treatment was performed following injection of anticancer agents 3 days after the inoculation of the T24 cells. DNA samples were obtained from the livers of the chick embryos, and the polymerase chain reaction technique was used to amplify a DNA fragment specific to the human beta-globin gene. The Southern hybridization method was used to evaluate the inhibitory effects of anticancer agents in combination with/without hyperthermia on T24 cells metastasized to the liver. The hyperthermia exerted an inhibitory effect on the growth of the T24 cells in the livers of the chick embryos, and this was dependent on the thermal dose. The antitumor effects of hyperthermia performed at 42.5 degrees C for 20 min and at 43.0 degrees C for 10 min were evidenced by 69.2% an 82.0% inhibition of the growth of the metastasized T24 cells, respectively, as compared with the growth of untreated T24 cell. Hyperthermia performed at 42.5 degrees C for 10 min alone produced 26.7% tumor growth inhibition, and these conditions for hyperthermia were subsequently used as a criterion for evaluating the effects of its combination with various anticancer agents. Adriamycin (20 micrograms/egg) alone, mitomycin C (10 micrograms/egg) alone, carboplatin (10 micrograms/egg) alone, and cisplatin (10 micrograms/egg) alone produced 13.5%, 58.9%, 27.3%, and 29.1% tumor growth inhibition, respectively. Adriamycin and mitomycin C applied in combination with hyperthermia showed additive inhibitory effects on the growth of the metastasized T24 cells in this chick embryo model. PMID- 7994795 TI - Prophylactic chemotherapy with intravesical instillation of adriamycin and oral administration of 5-fluorouracil after surgery for superficial bladder cancer. The Japanese Urological Cancer Research Group for Adriamycin. AB - The Japanese Urological Cancer Research Group for Adriamycin has conducted a series of clinical trials to investigate the efficacy and safety of prophylactic intravesical chemotherapy for superficial bladder cancer. In the third trial, reported herein, patients with recurrent bladder cancer or multiple primary cancer were selected and randomized to one of four groups using the envelope method after complete resection of the original tumors. Group A was given Adriamycin alone, group B received oral 5-fluorouracil (5-FU), group C was given Adriamycin and oral 5-FU, and group D served as the control group. Of the 544 patients registered, 331 were evaluable for the purpose of this study. The administration of 5-FU (group B) failed to prevent the recurrence of bladder tumors. Although group C (both Adriamycin and 5-FU) did not fare better than group A (Adriamycin only), Adriamycin was effective in preventing the recurrence of tumors, especially in high-risk patients with recurrent and multiple tumors. The risk of recurrence was reduced to 0.21 (95% confidence interval, 0.10-0.44) relative to the control group. There was no indication of a synergistic effect between 5-FU and Adriamycin. As side effects, cystitis syndrome was observed in 23%-30% of the patients in the Adriamycin groups and mild myelosuppression was observed in the 5-FU groups. PMID- 7994797 TI - Experiences with doxo/epirubicin and medroxyprogesterone acetate (MPA) in prostatic cancer. AB - Maximal androgen blockade (MAB) has been reported to prolong the time to progression and the duration of survival in metastatic prostatic cancer. The addition of epirubicin to MAB in such patients seems to improve the therapeutic results further. The beneficial effect of combining castration with epirubicin in metastatic cases appears questionable. In comparing the time to progression in patients treated with MAB +/- epirubicin versus castration +/- epirubicin or estramustine, many studies reveal similar figures. Whether the results after treatment are actually improved remains controversial. In hormone-refractory cases, medroxyprogesterone acetate (MPA) alone seems superior to estramustine or prednisolone treatment. Combining MPA and epirubicin improves the results, but even if the improvement is of clinical value, it is nonetheless of limited magnitude. PMID- 7994796 TI - Advanced bladder cancer: options of therapy. PMID- 7994798 TI - Outcome research and practice guideline development in healthcare reform. PMID- 7994799 TI - Task force on Research in Epidemiology and Prevention of Cardiovascular Diseases. PMID- 7994800 TI - Elevated donor cardiac troponin I. A marker of acute graft failure in infant heart recipients. PMID- 7994801 TI - DD genotype of the angiotensin-converting enzyme gene is a risk factor for left ventricular hypertrophy. AB - BACKGROUND: The cardiac renin-angiotensin system has been suggested to be involved in the development of left ventricular hypertrophy. In humans, a strong correlation has been found between plasma angiotensin I-converting enzyme (ACE) activity and the insertion/deletion (I/D) polymorphism of the ACE gene, which has been reported to be associated with myocardial infarction, ischemic and idiopathic dilated cardiomyopathy, sudden death in hypertrophic cardiomyopathy, and restenosis after percutaneous transluminal coronary angioplasty. In the present study, we examined the possibility that the genotype of the ACE gene might influence the development of left ventricular hypertrophy. METHODS AND RESULTS: The study population consisted of 268 subjects randomly selected from our outpatient clinic. In 142 subjects, left ventricular mass (LVM) was determined by echocardiogram. The genotype of the ACE gene was determined by the polymerase chain reaction. ANCOVA revealed that the genotype of the ACE gene had no effect on blood pressure. The percentage of the explained variance of LVM with variables including diastolic blood pressure (DBP, P = .0001), body mass index (BMI, P = .0001), sex (P = .0009), and the genotype of the ACE gene (P = .0017) was 34.61%. Significant differences in the effects of the genotype of the ACE gene on LVM were observed between the II and DD (P = .0004) and between the ID and DD (P = .0077) genotypes. The percentage of the explained variance of the LVM/ht ratio with variables including sex (P = .134), age (P = .3655), the genotype of the ACE gene (P = .0014), BMI (P = .0001), and DBP (P = .0001) was 31.25%. Significant differences in the effects of the genotype of the ACE gene on LVM/ht were observed between the II and DD genotypes (P = .0003) and between the ID and DD genotypes (P = .0091). CONCLUSIONS: In addition to BMI and DBP, the genotype of the ACE gene was a significant predictor of LVM and LVM/ht in our study population. PMID- 7994802 TI - Correlation between decreased myocardial glucose phosphorylation and the DNA mutation size in myotonic dystrophy. AB - BACKGROUND: Myotonic dystrophy, the most common form of adult dystrophy, has been shown to be caused by amplification of CTG triplet repeat in the 3' untranslated region of a protein kinase gene located on chromosome 19. Impaired glucose metabolism has been suggested as a possible explanation of brain and skeletal muscle involvement in this multisystem disease. We investigated whether myocardial glucose metabolism is impaired in myotonic dystrophy and whether this impairment is related to the size of the mutation. METHODS AND RESULTS: The myocardial metabolic rate for glucose (MMRGlu, mumol.min-1.g-1), K1 (blood-to tissue transfer constant), k2 (tissue-to-blood transfer constant), and k3 (phosphorylation rate constant) were determined in 7 control subjects and 12 patients with myotonic dystrophy by using parametric images generated from dynamic cardiac positron emission tomography (PET) and 18F-fluoro-2-deoxy-glucose studies. The expansion of the CTG triplet repeats was analyzed in patients with the probe cDNA25 after EcoRI digestion. Nonparametric tests were used to compare quantitative variables between control subjects and patients. The correlations between the size of the mutation and PET parameters were studied by linear regression. MMRGlu and k3 were significantly decreased in patients compared with control subjects (0.39 +/- 0.20 versus 0.64 +/- 0.25, P = .03, and 0.09 +/- 0.07 versus 0.24 +/- 0.21, P = .03, respectively), whereas K1 and k2 were not statistically different between control subjects and patients. MMRGlu and k3 correlate inversely with the length of the CTG triplet repeat (r = -.65 and P = .03 for MMRGlu, and r = -.85 and P = .001 for k3, respectively). CONCLUSIONS: In myotonic dystrophy, the observed reductions in MMRGlu and phosphorylation are inversely linked to the length of the mutation. This observation suggests that impaired modulation of a protein kinase involved in myocardial hexokinase activation may give a pathophysiological schema to relate the molecular defect and the abnormal myocardial metabolism in myotonic dystrophy. PMID- 7994803 TI - Evidence of genetic heterogeneity in Romano-Ward long QT syndrome. Analysis of 23 families. AB - BACKGROUND: The Romano-Ward long-QT Syndrome (LQTS) is an autosomal dominant inherited trait characterized by prolonged QT interval on ECG, life-threatening arrhythmias, syncope, and sudden death in affected individuals. A gene responsible for this disorder has been shown to be linked to the Harvey ras-1 locus (H-ras-1) DNA marker on the short arm of chromosome 11 (11p) in 7 families. The purpose of this study was to determine, by analyzing 23 families with LQTS for linkage to chromosome 11p, whether evidence exists for more than one gene causing LQTS (ie, locus heterogeneity). METHODS AND RESULTS: Twenty-three families (262 family members) were clinically evaluated using medical histories, ECGs, and Holter recordings. Each corrected QT interval (QTc) were determined using Bazett's formula. Blood for DNA extraction and cell line immortalization was obtained after informed consent. Southern blotting and polymerase chain reaction were performed, and linkage analysis carried out using the LINKAGE computer program (v 5.03). Genetic heterogeneity was determined using the HOMOG 2 (v 2.51) computer program. Twenty-three families were studied for evidence of linkage to chromosome 11p using the H-ras-1 locus probe pTBB-2 and multiple flanking markers, including tyrosine hydroxylase (TH). Two-point linkage analysis using pTBB-2 and TH markers was consistent with linkage in 15 of 23 families, with the maximum single-family LOD score of +3.038 occurring at theta = 0. However, 8 of 23 families had negative LOD scores, with the values in 4 families being less than -2 at theta = 0, consistent with exclusion of linkage. Analysis with the HOMOG program was consistent with genetic heterogeneity (P < .0001). Multipoint linkage data using pTBB-2 and TH were also examined for evidence of heterogeneity. HOMOG analysis of multipoint LOD scores from 100 cM surrounding the H-ras-1 locus also supported heterogeneity (P < .001). CONCLUSIONS: In the 23 families with LQTS analyzed for linkage to the H-ras-1 locus on chromosome 11p15.5, 15 of 23 families had LOD scores consistent with linkage. The remaining 8 of 23 families had negative LOD scores, 4 of which were definitively excluded from linkage. Thus, genetic heterogeneity is definitively (P < .001) demonstrated for this disorder. PMID- 7994804 TI - Long-term survival of medically treated patients in the Coronary Artery Surgery Study (CASS) Registry. AB - BACKGROUND: This study describes the impact of clinical, angiographic, and demographic characteristics on the long-term survival of Coronary Artery Surgery Study (CASS) patients while they were under medical treatment. Revascularization rates for the population are also provided. METHODS AND RESULTS: All CASS patients who had not received heart surgery before enrollment (23,467 patients) were included in this survival analysis while they were under medical treatment or surveillance. Follow-up time ranged from 0 to 17 years (median, 12 years). Long-term vital status is known for 95.8% of these patients. Log-rank tests, Kaplan-Meier survival curves, and Cox proportional-hazards regression are used to describe and assess the impact of patient characteristics on survival. Characteristics that had a significant impact on survival, in order of observed explanatory power, are age, number of diseased vessels, congestive heart failure score, smoking history, ejection fraction, sex, presence of left main coronary artery disease, presence of diabetes, left ventricular wall motion score, presence of other illnesses, history of myocardial infarction, and presence of left main equivalent disease. Overall, 12-year survival for patients with zero-, one-, two- and three-vessel disease is 88%, 74%, 59%, and 40%, respectively. Twelve-year survival for patients with at least one diseased vessel and ejection fractions in the ranges of 50% to 100%, 35% to 49%, and 0% to 34% is 73%, 54%, and 21%, respectively. High myocardial jeopardy, high anginal class, and two or three proximal diseased vessels characterize the profile of patients most likely to have received surgical treatment during follow-up. CONCLUSIONS: These results contribute to the understanding of the natural history of coronary artery disease and are also of historical interest. The poor survival of patients with three vessel disease and low ejection fractions continues to emphasize the importance of considering revascularization for these patients. PMID- 7994805 TI - Mortality within 24 hours of thrombolysis for myocardial infarction. The importance of early reperfusion. The GUSTO Investigators, Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries. AB - BACKGROUND: A paradoxical increased risk of death has been reported during the first 24 hours after thrombolysis for myocardial infarction. The mechanism of this phenomenon is not known, nor is its relation to the success or failure of reperfusion. The present study was a prospectively designed analysis of deaths occurring within the first 24 hours in the GUSTO trial. METHODS AND RESULTS: There were 41,021 patients enrolled in GUSTO, a randomized comparison of streptokinase with intravenous or subcutaneous heparin, accelerated tissue-type plasminogen activator (TPA), and combination of streptokinase and TPA. An angiographic mechanistic substudy examined reperfusion (using the TIMI flow grading criteria) 90 minutes after the assigned thrombolytic regimen was begun in 1567 patients. There were 1125 deaths (2.8%) within 24 hours ("early deaths") and 1726 additional deaths (4.2%) after 24 hours but within 30 days ("later deaths"). At the time of presentation, the most potent predictors of early death were hypotension and sinus tachycardia. In a multiple logistic regression model, lower systolic blood pressure, shorter height, higher heart rate, and the absence of prior smoking distinguished early death from later death. Reinfarction occurred in 26 patients (2.4%), shock in 572 patients (52%), atrioventricular block in 308 patients (28%), and tamponade in 106 patients (10%) dying early compared with 262 (15%), 788 (46%), 396 (23%), and 74 (4%) respective patients dying later. There were no differences in early mortality among the thrombolytic regimens for the first 6 hours after randomization. By 24 hours, however, mortality was 2.89% for streptokinase recipients, 2.84% for combination therapy recipients, and 2.36% for accelerated TPA recipients (P = .005). There was little difference among patients with differing flow grades in the infarct artery during the first 4 hours, although mortality was 2.35% for patients with flow grade 0 or 1, 2.92% for patients with flow grade 2, and 0.89% for patients with flow grade 3. CONCLUSIONS: Even with aggressive management regimens, mortality within the first 24 hours accounted for a large proportion of postthrombolytic deaths. Patients dying early were more likely to present with pump failure than were those dying later and were more likely to diet of events related to left ventricular dysfunction, although cardiac tamponade also accounted for a significant minority of these deaths. Thus, the severity of the clinical presentation rather than the underlying risk factors predicts early mortality. Based on the angiographic substudy data, it appears that rather than hastening early mortality, successful restoration of complete antegrade flow in the infarct-related artery protects against early death. PMID- 7994806 TI - Activation of complement and kinin systems after thrombolytic therapy in patients with acute myocardial infarction. A comparison between streptokinase and recombinant tissue-type plasminogen activator. AB - BACKGROUND: We have previously shown that treatment with streptokinase induces abrupt complement activation and transient neutropenia in patients with acute myocardial infarction (AMI). The purpose of this study was to compare the effects of two different thrombolytic agents--streptokinase (SK) and recombinant tissue type plasminogen activator (rTPA)--on activation of the complement and kinin systems in plasma of patients with AMI. METHODS AND RESULTS: Forty-one patients with AMI who were eligible for thrombolytic therapy were studied. Twenty-three patients were treated with streptokinase (1.5 million IU IV over 60 minutes) and 18 were treated with rTPA (8 with bolus of 10 mg IV, followed by 50 mg infused over 60 minutes and then 40 mg infused over 120 minutes; 10 patients were administered rTPA and heparin according to the accelerated infusion protocol indicated by the GUSTO study). C4a and C3a were measured by radioimmunoassay, soluble terminal complement components (SC5b-9) and anti-SK IgG antibodies were measured by ELISA. Cleaved high molecular weight kininogen (HK) was quantitated in plasma by SDS-PAGE and immunoblotting analysis. C4a levels were significantly and similarly increased in both groups, whereas the levels of C3a and SC5b-9 after rTPA infusion were only slightly elevated and were significantly lower than after SK. No differences were observed between patients treated with slow or accelerated rTPA regimens. The titer of antibodies to SK was highly correlated with the levels of C3a and SC5b-9, whereas a lesser correlation was observed with C4a. Treatment with rTPA did not induce the transient neutropenia observed after SK infusion. The cleavage products of HK were significantly greater after SK than after rTPA infusion. CONCLUSIONS: Our results show that both thrombolytic agents activate the classic complement pathway and that plasmin could be the common trigger for this phenomenon. A significant activation of the complement common pathway (from C3 to terminal components) was observed only with SK infusion and is attributable to the rapid formation of immunocomplexes between SK and anti-SK antibodies present in plasma as a consequence of previous streptococcal infections. The minimal activation of C5 component of the common pathway explains the absence of leukopenia in patients treated with rTPA. Cleavage of HK, larger after SK than after rTPA infusion, represents a condition enhancing the generation of bradykinin by kallikrein. The recent experimental data that indicate a damaging effect of complement activation on the infarcted zone and the contrasting favorable effect consequent to bradykinin formation raise some questions about the clinical importance of the different biological consequences of SK versus rTPA. PMID- 7994807 TI - Persistent thrombin generation in humans during specific thrombin inhibition with hirudin. AB - BACKGROUND: The degree to which antithrombotic drugs suppress thrombin generation is unknown. Because hirudin, unlike antithrombin III, binds intravascular thrombin rapidly and selectively to yield a circulating inactive complex of 3- to 4-hour half-life, we used intravenous hirudin in humans to investigate the course of thrombin generation during and early after anticoagulation with this potent, direct antithrombin. METHODS AND RESULTS: Intravascular thrombin was measured with an ELISA for the thrombin-hirudin complex formed during and for 18 hours after stopping a 6-hour infusion of hirudin at 0.1, 0.2, and 0.3 mg.kg-1.h-1 in three groups of six patients each. With free hirudin in 20- to 10,000-fold molar excess of thrombin and peak activated partial thromboplastin times of 2.3 to 3.0 times baseline, mean plasma thrombin-hirudin complex increased from 794 +/- 85 pg/mL (mean +/- SEM) 15 minutes after the start of the infusion to 1617 +/- 151 pg/mL at 6 hours of infusion to 2667 +/- 654 pg/mL at 24 hours. During the 24 hour observation period, plasma concentration of fragment 1.2 (the peptide released during conversion of prothrombin to thrombin) never fell below baseline but rather increased transiently during the hirudin infusion. Plasma concentrations of thrombin-antithrombin III complex (in ng/mL) decreased from 4.34 +/- 0.40 at baseline to 1.64 +/- 0.13 at 6 hours (P < .001) and gradually increased after stopping the infusion to 5.7 +/- 0.87 at 24 hours (nonsignificant compared with baseline). CONCLUSIONS: Measurement of thrombin-hirudin complex may be used as a marker of thrombin generation in humans. Persistent accumulation of thrombin-hirudin complex and generation of fragment 1.2 during and after completion of potent anticoagulation with hirudin suggest thrombin generation is not blocked by high-affinity thrombin inhibition. The persistent formation of thrombin during declining plasma levels of hirudin may contribute to the pathogenesis of rethrombosis early after antithrombin therapy or during inadequate anticoagulation. PMID- 7994808 TI - Fibrin formation and degradation in patients with arteriosclerotic disease. AB - BACKGROUND: The blood coagulation cascade was reported to be activated in patients with arteriosclerotic disease of the lower limbs (peripheral arterial disease, PAD). There is more thrombin and fibrin formation compared with healthy control subjects. In many studies, however, the presence of arteriosclerotic disease had not been thoroughly ruled out in the control group. Therefore, markers of the activation of the blood coagulation cascade were measured in patients with PAD and in a carefully defined control group, both groups being subjected to an exercise test. METHODS AND RESULTS: Twenty-two patients with angiographically documented PAD of grade II (Fontaine classification) and 13 control subjects in whom the presence of arteriosclerotic lesions was ruled out by noninvasive means in the carotid arteries, abdominal aorta, leg arteries, and coronary arteries took part in the study. Before and immediately after a treadmill stress test, the concentrations of prothrombin fragment F1 + 2 (F1 + 2), thrombin-antithrombin III complexes (TAT), fibrinopeptide A (FPA; this peptide was measured in spot urine also), and D-dimers were measured. Before exercise, the concentrations of F1 + 2 (1.0 +/- 0.6 versus 0.7 +/- 0.3 nmol/L), TAT (2.9 +/- 2.1 versus 1.9 +/- 0.8 micrograms/L), and D-dimers (318.2 +/- 270.1 versus 150.0 +/- 91.4 micrograms/L) were significantly higher in the patients with PAD compared with the healthy control subjects. FPA concentrations in plasma (1.9 +/- 1.0 versus 1.4 +/- 0.6 micrograms/L) and spot urine were not different, however. F1 + 2, FPA, and D-dimer concentrations correlated with the severity of the PAD as assessed by the ankle systolic blood pressure index (ABPI). The symptom-limited stress test did not lead to further activation of the blood coagulation cascade. However, concentrations of F1 + 2 (P < .001) and TAT (P < .01) after exercise correlated with the presence of ischemic changes in the stress-test ECG. CONCLUSIONS: There is evidence of enhanced thrombin formation in patients with PAD compared with an age- and sex-matched control group without clinical and sonographic evidence of arteriosclerosis. The thrombin formed, however, appears to be almost completely neutralized by antithrombin III. No direct evidence of fibrin formation was obtained, since the FPA concentrations were not different. In the patients with PAD, the higher concentrations of D dimers are indicative of in vivo fibrinolysis. Thus, some fibrin formation must be postulated to occur in patients with arteriosclerosis. PMID- 7994809 TI - Prognosis of patients with left ventricular dysfunction, with and without viable myocardium after myocardial infarction. Relative efficacy of medical therapy and revascularization. AB - BACKGROUND: The uptake of F-18 deoxyglucose into dysfunction segments after myocardial infarction identifies metabolically active (FDG+) or inactive (FDG-) myocardium. Although patients with FDG+ segments have been found to be at risk for adverse events, the prognostic significance of viable myocardium in relation to other influences on postinfarction prognosis, including revascularization, remain ill defined. The purpose of this study was to investigate the relative prognostic significance of FDG+ tissue and to establish whether myocardial revascularization in patients with viable tissue attenuates the risk of adverse outcome. METHODS AND RESULTS: One hundred thirty-seven patients with left ventricular dysfunction and resting perfusion defects after myocardial infarction underwent positron emission tomography with both dipyridamole stress Rb-82 perfusion imaging and FDG imaging. After the exclusion of 4 patients proceeding to transplantation, 2 with uninterpretable scans and 2 lost to follow-up, 129 patients were followed clinically for 17 +/- 9 months. Four groups were defined: patients with FDG+ dysfunctional myocardium who were revascularized (n = 49) or treated medically (n = 21) and those with FDG- segments who were revascularized (n = 19) or treated medically (n = 40). The groups of patients with FDG+ or FDG- findings, with and without revascularization, did not differ with respect to known determinants of postinfarction prognosis: age, left ventricular ejection fraction, or the prevalence of multivessel disease. Nonfatal ischemic events occurred in 48% of medically treated FDG+ patients compared with 8% of revascularized patients with FDG+ tissue (P < .001) and 5% of patients with FDG- myocardium (P < .001). Thirteen patients died from cardiac causes; 11 (85%) had a left ventricular ejection fraction of < 30%, and these patients were evenly distributed between FDG+ and FDG- groups. Using Cox's proportional hazards model, only the presence of FDG+ myocardium (odds ratio, 12.9; P < .001) and the absence of revascularization (odds ratio, 5.8; P = .002) independently predicted ischemic events, while only age (P = .02) and ejection fraction (P < .001) but not the presence of viable myocardium were predictive of death. CONCLUSIONS: Residual viable myocardium after myocardial infarction may act as an unstable substrate for further events unless it is revascularized. Despite this association, age and left ventricular dysfunction remained the strongest predictors of cardiac death after myocardial infarction in these patients with a spectrum of left ventricular dysfunction. PMID- 7994810 TI - Acute effects of nitrates on exercise testing in patients with syndrome X. Clinical and pathophysiological implications. AB - BACKGROUND: Sublingual nitrates are much more effective in relieving angina pectoris in patients with coronary artery disease than in patients with syndrome X, but it is not known whether their effect on exercise tolerance is also different in these two groups of patients. METHODS AND RESULTS: Treadmill exercise testing was performed before and after administration of sublingual isosorbide dinitrate (ISDN, 5 mg) in 18 patients with syndrome X (effort angina and normal coronaries, group X) and in 33 patients with documented coronary artery disease (group C). As a selection criterion, all patients had ST-segment depression > or = 1 mm on the control exercise test. Compared with the control test, the main differences in the two groups observed during the exercise test after administration of ISDN were (1) heart rate at 1-mm ST-segment depression was higher (126 +/- 25 versus 104 +/- 15 beats per minute [bpm], P < .01) in group C, whereas it was not different (125 +/- 15 versus 126 +/- 16 beats per minute) in group X; (2) the rate-pressure product at 1-mm ST-segment depression, the time to 1-mm ST-segment depression, and the exercise duration were significantly improved in group C (P < .01 for all) but were worsened in group X (18,047 +/- 4159 versus 20,535 +/- 4507 bpm . mm Hg, P = .014; 268 +/- 312 versus 429 +/- 214 seconds, P < .01; 494 +/- 279 versus 622 +/- 194 seconds, P = .013, respectively); (3) a normalization of the ECG (no ST-segment depression) was obtained in 10 patients (30%) of group C but in only 1 (5%) of group X (P < .01); (4) angina was prevented in 10 of 19 patients of group C but in no patient of group X (P < .01). CONCLUSIONS: In patients presenting with anginal chest pain, the effects of sublingual nitrates on exercise testing appear to be clinically useful to distinguish patients with coronary artery stenoses from patients with syndrome X. Indeed, worsening of exercise tolerance is highly predictive of normal coronary arteries. Furthermore, the failure of nitrates to improve exercise tolerance in patients with syndrome X suggests that a deficiency in coronary prearteriolar nitric oxide production is unlikely to play a key role in the pathophysiology of the syndrome. PMID- 7994811 TI - Mechanism of exercise hypotension in patients with ischemic heart disease. Role of neurocardiogenically mediated vasodilation. AB - BACKGROUND: Exercise-induced hypotension in patients with coronary artery disease (CAD) has been considered to be due to an inability to achieve an adequate increase in cardiac output to match the demands of exercise. We investigated 10 consecutive patients (9 men and 1 woman; age, 38 to 71 years; mean, 52 years) with angiographically documented CAD and exercise-induced hypotension (EIH) (BPPeak < BPRest). Ten approximately age- and sex-matched patients with documented CAD and normal exercise blood pressure response (NBP) served as control subjects. METHODS AND RESULTS: Nine patients with EIH and all 10 control subjects underwent forearm plethysmography and radionuclide ventriculography (RNV) during semierect cycle exercise. Forearm vascular resistance (FVR) fell by 35 +/- 21% in exercise-induced hypotension patients versus an increase of 78 +/- 65% in patients with an NBP response (P < .0001). Left ventricular ejection fraction increased by 5.1 +/- 7.5% in the group with EIH versus a fall of 4.1 +/- 6.2% in the control group (P = .004). Cardiac output at peak exercise (RNV) increased by 2.2 +/- 0.89-fold in the group with EIH versus 1.49 +/- 0.47-fold in the control group (P = .04). The tenth patient in the group with EIH underwent invasive hemodynamic evaluation during erect exercise. Systolic blood pressure fell (136/80Rest to 50/40Peak) and cardiac output (Fick) tripled, whereas calculated systemic vascular resistance decreased by a factor of 10. Successful angioplasty to an isolated circumflex lesion resulted in resolution of symptoms and abnormal hemodynamic responses during exercise. CONCLUSIONS: Abnormal vasodilation associated with a normal or even increased rather than decreased cardiac output response appears to be an important mechanism underlying EIH in some patients with CAD. In the present study, this appears to have been the dominant mechanism in 8 and contributory in 2 of the consecutive patients studied. PMID- 7994812 TI - Trapidil (triazolopyrimidine), a platelet-derived growth factor antagonist, reduces restenosis after percutaneous transluminal coronary angioplasty. Results of the randomized, double-blind STARC study. Studio Trapidil versus Aspirin nella Restenosi Coronarica. AB - BACKGROUND: Trapidil is an antiplatelet drug with specific platelet-derived growth factor antagonism and antiproliferative effects in the rat and rabbit models after balloon angioplasty. METHODS AND RESULTS: The Studio Trapidil versus Aspirin nella Restenosi Coronarica (STARC) is a multicentric, randomized, double blind trial to assess the effects of trapidil in angiographic restenosis prevention after percutaneous transluminal coronary angioplasty (PTCA). Patients received either trapidil 100 mg TID or aspirin at the same dosage at least 3 days before angioplasty and for 6 months thereafter. Coronary angiograms before PTCA, after PTCA, and at 6-month follow-up were quantitatively analyzed with manual calipers. Of the initial 384 patients recruited, 254 were evaluable for restenosis analysis (128 trapidil, 126 aspirin). Restenosis, defined as a loss of initial percent gain after PTCA of at least 50% (primary end point), occurred in 24.2% of the trapidil group and 39.7% of the aspirin group (P < .01). A similar result was obtained when restenosis per vessel was considered (trapidil, 23.3%; aspirin, 36.9%; P = .018). Clinical events at follow-up were similar in the two groups except that recurrent angina was significantly more frequent in the aspirin group, 43.7% versus 25.8% in the trapidil group (P < .01). Trapidil was well tolerated: only 6 patients had to discontinue the drug because of side effects, which was not different from the aspirin group. CONCLUSIONS: Trapidil reduces restenosis after PTCA at the dosage of 100 mg TID and favorably influences the clinical outcome thereafter. PMID- 7994813 TI - Four-year experience with Palmaz-Schatz stenting in coronary angioplasty complicated by dissection with threatened or present vessel closure. AB - BACKGROUND: Abrupt vessel closure after percutaneous transluminal coronary angioplasty (PTCA) is associated with major adverse events. Different surgical and nonsurgical approaches have been advocated to treat or prevent this complication. This study summarizes our 4-year experience with Palmaz-Schatz stenting for the management of 339 patients with present or threatened occlusion after PTCA. METHODS AND RESULTS: Stent implantation was attempted in a total of 339 and 4959 patients with PTCA during the study period and was successful in 327 (96.5%). During the follow-up, events like death, myocardial infarction, need for revascularization (bypass surgery and repeat in-stent angioplasty), and major vascular complications were recorded. Angiographic follow-up at 6 months was performed in 89.3% of the eligible patients. As part of an initial policy, stenting was intended as a bridge to nonemergency bypass surgery in 26 patients. In 301 patients for whom stenting was intended as permanent treatment, early clinical course (first 4 weeks) was characterized by a 1.3% cardiac mortality and a 4.0% nonfatal myocardial infarction rate; bypass surgery was necessary in 1%, and 6.3% required early repeat PTCA. Surgical repair for peripheral vascular complications was required in 5.6%, and major bleeding events were encountered in 9%. The incidence of subacute stent closure was 6.9%, with subsequent recanalization successful in 86%; subacute stent closure was predicted by presence of vessel occlusion before stenting and localization of the stent in a vessel other than the right coronary artery. Survival rate at 2 years was 95.4%, survival without myocardial infarction was 91.1%, and event-free survival was 70.7%. Survival at 2 years was lower for patients with stents in bypass vein grafts and with myocardial infarction after stenting. Six-month control angiography revealed a restenosis rate of 29.6%. CONCLUSIONS: Patients with present or threatened occlusion after PTCA may benefit from Palmaz-Schatz stenting. It is associated with a low mortality and myocardial infarction rate and with a long-term event-free rate comparable to that of uncomplicated PTCA. PMID- 7994814 TI - Increased coronary perforation in the new device era. Incidence, classification, management, and outcome. AB - BACKGROUND: The incidence of coronary perforation using new percutaneous revascularization techniques may be increased compared with PTCA. Still, perforation is uncommonly reported, and the optimal management and expected outcome remain unknown. The objectives of the study were to determine the incidence of coronary perforation using balloon angioplasty (percutaneous transluminal coronary angioplasty, PTCA) and new revascularization techniques and to develop optimal strategies for its management based on classification and outcome. METHODS AND RESULTS: Eleven sites with frequent use of new revascularization devices and prospective coding of consecutive procedures for coronary perforation during 1990 to 1991 contributed to a perforation registry. Patients with perforation were matched by device with an equal-sized cohort without perforation. Data were collected centrally, and all procedural cineangiograms were reviewed at a core angiographic laboratory. A classification scheme based on angiographic appearance of the perforation (I, extraluminal crater without extravasation; II, pericardial or myocardial blushing; III, perforation > or = 1-mm diameter with contrast streaming; and cavity spilling) was evaluated as a predictor of outcome and as a basis for management. Perforation was observed in 62 of 12,900 procedures reported (0.5%; 95% confidence interval, 0.4% to 0.6%), more commonly with devices intended to remove or ablate tissue (atherectomy, laser) than with PTCA (1.3%, 0.9% to 1.6% versus 0.1%, 0.1% to 0.1%; P < .001). The perforation population was notable for its advanced age (67 +/- 10 years) and high incidence of female sex (46%) (both P < .001 compared with patients without perforation). Perforation could be treated expectantly or with PTCA but without cardiac surgery in 85%, 90%, and 44% of class I, II, and III perforations, respectively. Class I perforations (n = 13, 21%) were associated with death in none, myocardial infarction in none, and tamponade in 8%. The incidences of these adverse events were 0%, 14%, and 13% in class II perforations (n = 31, 50%) and 19%, 50%, and 63% in non-cavity spilling class III perforations, respectively (n = 16, 26%). Two of the 15 instances of cardiac tamponade (13%) were delayed, occurring within 24 hours after dismissal from the catheterization laboratory. CONCLUSION: The incidence of perforation, while low, is increased with new devices. Women and the elderly are at highest risk. The clinical risk after perforation can be classified angiographically, but even low-risk perforations occasionally have poor clinical outcome. Patients should be observed for delayed cardiac tamponade for at least 24 hours. PMID- 7994815 TI - Long-term results of dual-chamber (DDD) pacing in obstructive hypertrophic cardiomyopathy. Evidence for progressive symptomatic and hemodynamic improvement and reduction of left ventricular hypertrophy. AB - BACKGROUND: We previously reported that 6 to 12 weeks of dual-chamber (DDD) pacing results in clinical and hemodynamic improvement in obstructive hypertrophic cardiomyopathy (HCM). This study examines the long-term results of DDD pacing in obstructive HCM. METHODS AND RESULTS: DDD devices were implanted in 84 patients (mean age, 49 +/- 16 years) with obstructive HCM and severe drug refractory symptoms. At a mean follow-up of 2.3 +/- 0.8 years (maximum, 3.5 years), the New York Heart Association (NYHA) functional class had improved significantly (1.6 +/- 0.6 versus 3.2 +/- 0.5, P < .00001). Symptoms were eliminated in 28 patients (33%), improved in 47 patients (56%), but remained unchanged in 7 patients (8%). Two patients died suddenly (97% cumulative 3-year survival rate). In 74 patients with significant left ventricular outflow tract (LVOT) obstruction at rest, the LVOT gradients were significantly reduced at follow-up (27 +/- 31 versus 96 +/- 41 mm Hg, P < .00001). Symptoms and provokable LVOT gradients were also reduced in all 10 patients without significant resting but with provokable LVOT obstruction. Persistence of the LVOT obstruction and symptoms was attributed to inability to pre-excite the interventricular septum (n = 8) and onset of atrial fibrillation (n = 7). Fifty patients had two cardiac catheterization evaluations, 3 +/- 1 and 16 +/- 4 months after implantation of a pacemaker. In this subgroup, the NYHA functional class improved from 3.2 +/- 0.5 at baseline to 1.8 +/- 0.7 at the initial evaluation (P < .00001), but with a further significant improvement at the second evaluation: 1.4 +/- 0.6, P < .001. This symptomatic improvement was associated with progressive reduction of LVOT gradient at the two evaluations: baseline, 100 +/- 47 mm Hg; first evaluation, 41 +/- 36 mm Hg (P < .0001); and second evaluation, 29 +/- 34 mm Hg (P < .01). Despite the presence of left bundle branch block, DDD pacing reduced LVOT obstruction significantly in 15 patients (LVOT gradient, baseline 89 +/- 36 mm Hg versus 18 +/- 26 mm Hg at follow-up, P < .0001). There was a weak but significant correlation between the reduction in LVOT gradients accomplished by AV pacing before implantation of DDD device and the eventual reduction in LVOT gradients recorded at the follow-up evaluation (r = .38, P = .0017). Echocardiography demonstrated significant thinning of the anterior septum and distal anterior LV wall in the absence of deterioration of LV systolic function. CONCLUSIONS: (1) Although most of the improvement of symptoms and hemodynamic indexes occurs during the first few months of DDD pacing, further changes are often observed a year later; (2) DDD pacing is associated with an excellent prognosis in a subgroup of severely disabled patients, many of whom present with syncope or presyncope; (3) baseline pacing studies are not essential to identify patients who may benefit from pacing; (4) preexisting left bundle branch block is compatible with severe LVOT obstruction, and DDD pacing is also beneficial in this subgroup; (5) DDD pacing reduces both resting and provokable LVOT obstruction; (6) additional therapy, for example, radiofrequency ablation of the AV node, may be necessary in some patients either to preexcite the interventricular septum or to control atrial fibrillation; and (7) although LV hypertrophy has been considered a primary feature of HCM, pacing appears to reverse LV wall thickness in a significant subset of adult HCM patients. PMID- 7994816 TI - Prognosis of asymptomatic patients with hypertrophic cardiomyopathy and nonsustained ventricular tachycardia. AB - BACKGROUND: In the early 1980s, studies performed in highly selected referral patients with hypertrophic cardiomyopathy reported a strong association between the presence of brief episodes of ventricular tachycardia (VT) on ambulatory ECG monitoring and sudden death. These observations led to antiarrhythmic treatment in many patients with hypertrophic cardiomyopathy and brief episodes of VT. In recent years, however, a growing awareness of the potential arrhythmogenic effects of antiarrhythmic medications has raised doubts regarding such a therapeutic approach, particularly in less selected and lower-risk patient populations. METHODS AND RESULTS: In the present study, we examined the prognostic significance of nonsustained VT in a population of 151 patients with hypertrophic cardiomyopathy who were asymptomatic or had only mild symptoms at the time of their initial ambulatory ECG recording. Of the 151 study patients, 42 had episodes of VT and 109 did not. The runs of VT ranged from 3 to 19 beats, with 35 patients (83%) having < 10 beats. The number of runs of VT ranged from 1 to 12 in 24 hours, with 36 patients (86%) having < or = 5 episodes of VT. Thus, in most patients, the episodes of VT were brief and infrequent. Follow-up averaged 4.8 years. Of the 151 study patients, 6 died suddenly, 3 in the group with VT and 3 in the group without VT. Two other patients, both in the group without VT, died of congestive heart failure. The total cardiac mortality rate was 1.4% per year in the patients with VT (95% CI, 0.4% to 3.5%) and 0.9% in those without VT (95% CI, 0.4% to 2.0%; P = .43). The relative risk of cardiac death for patients with VT was 1.4 compared with patients without VT (95% CI, 0.6 to 6.1). The sudden death rate was 1.4% per year in the patients with VT (95% CI, 0.4% to 3.5%) and 0.6% in those without VT (95% CI, 0.2% to 1.5%; P = .24). The relative risk of sudden death for patients with VT compared with those without VT was 2.4 (95% CI, 0.5 to 11.9). Of the 151 patients included in the study, 88 (58%) remained asymptomatic and were not treated with cardioactive medications during follow-up. Of these 88 patients, 20 were in the group with VT and 68 in the group without VT. None of these patients died. CONCLUSIONS: Our results show that cardiac mortality is low in patients with hypertrophic cardiomyopathy who are asymptomatic or only mildly symptomatic and have brief and infrequent episodes of VT on ambulatory ECG monitoring. Our findings also suggest that brief and infrequent episodes of VT should not be considered, per se, an indication for antiarrhythmic treatment in such patients. PMID- 7994817 TI - Angiotensinergic versus nonangiotensinergic hemodynamic effects of converting enzyme inhibition in patients with chronic heart failure. Assessment by acute renin and converting enzyme inhibition. AB - BACKGROUND: The contribution of nonangiotensinergic effects of converting enzyme inhibitors to their hemodynamic effects in patients with chronic heart failure is not clear. A comparison of the effects of renin and converting enzyme inhibition should help to clarify this issue. METHODS AND RESULTS: Thirty-six patients with chronic heart failure (New York Heart Association class II or III) were randomly assigned to receive double-blind either intravenous placebo, the renin inhibitor remikiren, or the converting enzyme inhibitor enalaprilat followed by coinfusion of a second placebo infusion, the addition of remikiren to enalaprilat, or the addition of enalaprilat to remikiren, respectively. Systemic hemodynamics (Swan Ganz and radial artery catheters) were measured before (rest and submaximal recumbent bicycle ergometry), during (rest), and at the end (rest and exercise) of each 45-minute single- or combination-infusion period. Placebo did not change hemodynamics or renin activity. Effective inhibition of the renin-angiotensin system by remikiren and enalaprilat was indicated by increases of plasma immunoreactive renin together with rapid and complete inhibition of renin activity after remikiren and an increase after enalaprilat (all P < or = .05). Remikiren and enalaprilat rapidly and to a similar extent reduced resting blood pressure through a reduction of systemic vascular resistance, and these changes were significantly correlated to baseline plasma renin activity. Both compounds also decreased pulmonary artery, pulmonary capillary wedge, and right atrial pressures to a similar extent (P < .05). During exercise, pulmonary capillary wedge and right atrial pressures were equally reduced and stroke volume index was increased with remikiren and enalaprilat (P < .05) for both). The combination of converting enzyme with renin inhibition or vice versa did not cause additional hemodynamic changes. CONCLUSIONS: Specific renin inhibition in patients with chronic heart failure produces short-term hemodynamic effects that are almost indistinguishable from those of converting enzyme inhibition. This finding and the lack of additional effects of converting enzyme inhibition added to renin inhibition suggest that nonangiotensinergic effects of converting enzyme inhibitors do not play a significant role in their short-term hemodynamic effects in patients with chronic heart failure. PMID- 7994818 TI - Reduced peak aerobic capacity in asymptomatic left ventricular systolic dysfunction. A substudy of the studies of left ventricular dysfunction (SOLVD). SOLVD Investigator. Studies of Left Ventricular Dysfunction. AB - BACKGROUND: Peak oxygen consumption is reduced in patients with symptomatic congestive heart failure, but functional capacity of patients with asymptomatic left ventricular systolic dysfunction has not been assessed by measurement of peak oxygen consumption attained during graded exercise testing. METHODS AND RESULTS: Peak oxygen consumption, that is, aerobic capacity (VO2, mL/kg per minute), was determined during graded treadmill exercise using the modified Naughton protocol in 40 patients with left ventricular systolic dysfunction (mean ejection fraction ranging from 14% to 35%; mean, 29%) who, while not receiving any cardiac medications, were totally asymptomatic, and in 41 age-matched normal subjects. Peak exercise duration and VO2 were significantly lower in patients with asymptomatic left ventricular systolic dysfunction than in normal subjects (948 +/- 273 versus 1239 +/- 372 seconds, P < .001, and 22.1 +/- 5.9 versus 29.8 +/- 7.7 mL/kg per minute, respectively, P < .001), while asymptomatic patients and normal subjects reached similar respiratory equivalents (1.14 +/- 0.11 versus 1.11 +/- 0.11 [NS]) and level of perceived exertion, using the modified Borg scale (7.4 +/- 2.6 versus 8.1 +/- 1.5 [NS]). Heart rate, systemic blood pressure, and oxygen pulse response to peak exercise were significantly lower in asymptomatic patients than in normal subjects. CONCLUSIONS: Although patients with left ventricular systolic dysfunction can be totally asymptomatic in their daily activities, they have experienced a substantial reduction in peak aerobic capacity when compared with normal subjects of similar age. PMID- 7994819 TI - Intracardiac angiotensin-converting enzyme inhibition improves diastolic function in patients with left ventricular hypertrophy due to aortic stenosis. AB - BACKGROUND: Cardiac hypertrophy is associated with elevated intracardiac angiotensin-converting enzyme activity, which may contribute to diastolic dysfunction. METHODS AND RESULTS: We infused enalaprilat (0.05 mg/min) for 15 minutes into the left coronary arteries of 20 adult patients with left ventricular (LV) hypertrophy due to aortic stenosis (mean aortic valve area, 0.7 +/- 0.2 cm2) and 10 patients with dilated cardiomyopathy (mean ejection fraction, 35 +/- 4%) and assessed (1) simultaneous changes in LV micromanometer pressure and dimensions, (2) LV regional wall motion analyzed by the area method, and (3) Doppler flow-velocity profiles. Systemic neurohormonal activation did not occur with the selective left coronary artery infusion; there were no changes in plasma renin activity, angiotensin-converting enzyme activity, or atrial natriuretic peptide. In patients with aortic stenosis, LV end-diastolic pressure declined from 25 +/- 2 to 20 +/- 2 mm Hg (P < .05). LV pressure-volume and LV pressure dimension relations showed downward shifts by ventriculography and echocardiography, respectively, indicating improved diastolic distensibility. Regional area change during isovolumic relaxation increased in the anterior segments perfused with enalaprilat but decreased in the inferior segments, indicating acceleration of isovolumic relaxation in the anterior segments and reciprocal shortening in the inferior segments. Regional peak filling rate increased in the anterior segments but not in the inferior segments, and the regional area stiffness constant decreased in the anterior segments but not in the inferior segments. There were no changes in heart rate, cardiac output, or right atrial pressure, excluding alterations in right ventricular/pericardial constraint. In contrast, in the patients with dilated cardiomyopathy the decrease in LV end-diastolic pressure from 22 +/- 2 to 18 +/- 2 mm Hg (P < .05) was accompanied by a significant fall in right atrial pressure (9 +/- 1 to 6 +/- 1 mm Hg), implicating alterations in pericardial constraint. The patients with dilated cardiomyopathy showed no improvement in regional diastolic relaxation, filling, or distensibility. CONCLUSIONS: Intracoronary enalaprilat at a dosage that did not cause systemic neurohormonal activation improved LV diastolic chamber distensibility and regional relaxation and filling in patients with LV hypertrophy due to aortic stenosis. In contrast, these effects of intracoronary enalaprilat on diastolic function were not observed in patients with dilated cardiomyopathy who did not have concentric hypertrophy. These observations support the hypothesis that the cardiac renin-angiotensin system is activated in patients with concentric pressure-overload hypertrophy and that this activation may contribute to impaired diastolic function. PMID- 7994820 TI - Systolic and diastolic dysfunction in patients with clinical diagnosis of dilated cardiomyopathy. Relation to symptoms and prognosis. AB - BACKGROUND: Dilated cardiomyopathy is an important cause of morbidity and mortality among patients with congestive heart failure. Hemodynamic and prognostic characterization are critical in guiding selection of medical and surgical therapies. METHODS AND RESULTS: A cohort of 102 patients with the clinical diagnosis of dilated cardiomyopathy who underwent echocardiographic examination between 1986 and 1990 was identified and followed up through July 1, 1991. Patients with moderate or severe symptoms had lower indices of systolic function and greater left atrial and right ventricular dilation. Mitral inflow Doppler signals were characterized by a restrictive left ventricular filling pattern. In multivariate logistic regression analysis, deceleration time, ejection fraction, and peak E velocity were independently associated with symptom status. Over a mean follow-up of 36 months, 35 patients died. Kaplan-Meier estimated survival at 1, 2, and 4 years was 84%, 73%, and 61%, respectively, and was significantly poorer than that of an age- and sex-matched population. The subgroup with an ejection fraction < 0.25 and deceleration time < 130 milliseconds had a 2-year survival of only 35%. The subgroup with ejection fraction < 0.25 and deceleration time > 130 milliseconds had an intermediate 2 year survival of 72%, whereas patients with an ejection fraction > or = 0.25 had 2-year survivals > or = 95% regardless of deceleration time. In multivariate analysis, ejection fraction and systolic blood pressure were independently predictive of subsequent mortality. Mitral deceleration time was significant in univariate analysis. CONCLUSIONS: In patients with the clinical diagnosis of dilated cardiomyopathy, markers of diastolic dysfunction correlated strongly with congestive symptoms, whereas variables of systolic function were the strongest predictors of survival. Consideration of both ejection fraction and deceleration time allowed identification of subgroups with divergent long-term prognoses. PMID- 7994821 TI - Cardiovascular effects of inhaled nitric oxide in patients with left ventricular dysfunction. AB - BACKGROUND: Pulmonary vascular resistance (PVR) is frequently elevated in patients with advanced heart failure. Nitric oxide (NO), which contributes to the activity of endothelium-derived relaxing factor, causes relaxation of pulmonary arteries and veins in vitro. Inhalation of NO gas causes pulmonary vasodilation in patients with primary and secondary forms of pulmonary hypertension. METHODS AND RESULTS: To test the hypothesis that inhalation of NO gas lowers PVR in patients with heart failure, we studied the hemodynamic effects of a 10-minute inhalation of NO (80 ppm) in 19 patients with New York Heart Association class III (n = 5) and class IV (n = 14) heart failure due to left ventricular (LV) dysfunction. Although inhalation of NO had no effect on pulmonary artery pressures, the PVR decreased by 31 +/- 7% (P < .001) due to a 23 +/- 7% increase (P < .001) in pulmonary artery wedge pressure and despite a 4 +/- 2% (P < .05) decrease in cardiac index. The magnitude of the decrease in PVR with inhaled NO was inversely related (r = -.713; P < .001) to the baseline PVR. Inhaled NO had no effect on heart rate, systemic arterial pressure, systemic vascular resistance, or LV peak +dP/dt or -dP/dt. CONCLUSIONS: In patients with heart failure due to LV dysfunction, inhalation of NO causes a decrease in the PVR associated with an increase in LV filling pressure. These findings predict that inhaled NO, if used alone at this dose (80 ppm), may have adverse effects in patients with LV failure. PMID- 7994822 TI - Cardiac hypertrophy, aortic compliance, peripheral resistance, and wave reflection in end-stage renal disease. Comparative effects of ACE inhibition and calcium channel blockade. AB - BACKGROUND: We wished to assess the respective roles of the antihypertensive and blood pressure (BP)-independent effects of antihypertensive drugs on arterial hemodynamics and left ventricular hypertrophy (LVH) in end-stage renal disease (ESRD) patients. METHODS AND RESULTS: In a double-blind study, 24 ESRD patients with LVH were randomized to 12 months' administration of either the angiotensin converting enzyme (ACE) inhibitor perindopril (n = 14) or the calcium channel blocker nitrendipine (n = 10). Repeated measurements of the following parameters were performed: BP (mercury sphygmomanometry), left ventricular mass (LVM, echocardiography), cardiac output (aortic cross-section and velocity integral), total peripheral resistance (cardiac output and mean BP), aortic and large-artery compliance (pulse wave velocity, Doppler flowmeter), and arterial wave reflections (augmentation index, applanation tonometry). Radioimmunoassay was used to determine plasma renin activity, aldosterone, and plasma catecholamine levels. Two-way (time-treatment) ANOVA for repeated measures was used for statistical analysis. Perindopril and nitrendipine induced significant and similar decreases in BP, total peripheral resistance (P < .001), aortic and arterial pulse wave velocities (P < .001), and arterial wave reflections (P < .01). At baseline, the two groups had LVH mostly due to increased LV end diastolic diameter (LVEDD) (perindopril, 54.3 +/- 1.4 and nitrendipine, 54.3 +/ 2.4 mm) with near-normal mean LV wall thickness (perindopril, 11.4 +/- 0.3 and nitrendipine, 11.2 +/- 0.4 mm). A decrease in LVM was observed only in patients receiving perindopril (from 317 +/- 18 to 247 +/- 21 g) (time-treatment interaction, P = .036). Nitrendipine had no significant effect on LVM (314 +/- 29 versus 286 +/- 32 g). The decrease in LVM observed with perindopril was associated with a reduction in LVEDD (49.9 +/- 1.6 versus 54.3 +/- 1.4 mm after 12 months) (time-treatment interaction, P = .04), while the mean LV wall thickness was unchanged (11.4 +/- 0.3 versus 10.5 +/- 0.5 mm). Cardiac alterations were not correlated with changes in BP or with alterations in plasma renin activity or aldosterone or catecholamine levels. CONCLUSIONS: In ESRD patients with LVH, ACE inhibition decreases LVM independently of its antihypertensive effect and of associated alterations in arterial hemodynamics. The decrease in LVM was due primarily to a decrease in LV volume, which may have resulted in these patients from chronic volume overload. PMID- 7994823 TI - Abnormal diurnal variation of blood pressure, cardiac output, and vascular resistance in cardiac transplant recipients. AB - BACKGROUND: An attenuated or absent nocturnal decline in blood pressure has repeatedly been documented in cardiac transplant recipients. The present study was aimed at investigating the hemodynamic mechanism underlying this abnormality. METHODS AND RESULTS: In 23 cardiac transplant recipients (11 to 36 months after transplantation) and in 23 control subjects matched for age and 24-hour mean arterial pressure, invasive 24-hour ambulatory blood pressure was measured by means of the Oxford technique. Beat-to-beat relative values of stroke volume were determined by means of a pulse-contour method, and relative changes of cardiac output (stroke volume x heart rate) and total peripheral vascular resistance (blood pressure/cardiac output) over the 24-hour period were calculated. The nocturnal decline in blood pressure was 20 +/- 8% (mean +/- SD) in control subjects but only 5 +/- 9% (P < .001) in cardiac transplant recipients. In control subjects, the nocturnal decline in blood pressure was associated with a nocturnal fall in cardiac output of 24 +/- 13%, whereas vascular resistance compared with daytime value did not change. The small nocturnal decline in blood pressure in cardiac transplant recipients was associated with an attenuated nocturnal fall in cardiac output of 14 +/- 12% (P < .05 versus control subjects). In addition, vascular resistance compared with daytime value was increased by 9 +/- 9% (P < .05) during the night. Both in cardiac transplant recipients and in control subjects, the nocturnal changes in blood pressure were correlated with the nocturnal changes in cardiac output but not with the nocturnal changes in total peripheral vascular resistance. CONCLUSIONS: This study confirms the attenuated nocturnal fall in blood pressure in cardiac transplant recipients. Hemodynamically, this attenuated blood pressure decline is characterized by a reduced nocturnal fall in cardiac output, and it is associated with a nocturnal increase in vascular resistance. PMID- 7994824 TI - Radiofrequency ablation of atrial flutter. Efficacy of an anatomically guided approach. AB - BACKGROUND: Previous reports have shown that radiofrequency ablation can terminate atrial flutter and prevent recurrences. However, different methods have been used, and the current experience remains limited. The objective of the present study was to determine the efficacy of radiofrequency ablation of atrial tissue in patients with atrial flutter using an anatomically guided approach. METHODS AND RESULTS: We treated 22 patients aged 30 to 73 years. Atrial flutter was recurrent for a mean of 5 years despite the administration of multiple antiarrhythmic drugs. Radiofrequency current was directed to the atrial isthmus between the inferior vena cava and the tricuspid ring, regardless of the morphology of local electrograms. Radiofrequency energy was applied during typical atrial flutter in 12 patients, atypical atrial flutter in 2 patients, and successively both forms in 8 patients. In 19 patients, atrial flutter abruptly terminated. In 3 patients, atrial flutter persisted despite 37, 48, and 25 applications, respectively. Atrial recordings demonstrated that atrial flutter termination occurred as a consequence of conduction block at the site of radiofrequency energy application, regardless of the type of atrial flutter. The number of applications before termination ranged from 1 to 82 (mean, 32). Atrial flutter could no longer be induced in every case. There were no complications. During a 13-month mean follow-up, atrial flutter recurred in only 2 of the 19 patients who had a successful ablation. Four patients experienced chronic atrial fibrillation, and 2 of them returned to sinus rhythm with antiarrhythmic therapy. CONCLUSIONS: Radiofrequency ablation of atrial flutter using anatomic guidance is feasible and effective. Further experience is needed to delineate its role as an alternative approach to the management of refractory atrial flutter. PMID- 7994825 TI - Radiofrequency ablation of slow pathway in patients with atrioventricular nodal reentrant tachycardia. Do arrhythmia recurrences correlate with persistent slow pathway conduction or site of successful ablation? AB - BACKGROUND: Residual slow pathway conduction in the form of persistent jump in the atrioventricular (AV) conduction time or atrial echo beats is a common finding after successful radiofrequency (RF) ablation of the slow pathway in patients with AV nodal reentrant tachycardia (AVNRT). Sites of successful RF ablation of the slow pathway may be located anteriorly in the tricuspid annulus (cephalad to the coronary sinus os) or posteriorly (at, within, or caudal to the coronary sinus os). The aim of this study was to investigate whether arrhythmia recurrences correlate with persistent slow pathway conduction or site of successful ablation. METHODS AND RESULTS: Among 55 patients with symptomatic AVNRT having RF ablation, 23 patients (42%) (group 1) had evidence of persistent dual AV nodal pathway physiology and/or echo beats, whereas in 32 patients (group 2), slow pathway conduction had been completely eliminated. With regard to ablation sites, 14 patients (25%) (group A) had their slow pathway successfully ablated at an inferoposterior site, whereas in 41 patients (group B), the ablation site was located anteriorly to the coronary sinus os. The study patients included 17 men and 38 women, aged 37 +/- 18 years. The electrophysiological study and RF ablation were performed in a single session in 50 patients (91%). After the first session, the technique was successful in all patients (100%), with elimination of AVNRT and without affecting AV conduction. A mean of 9 +/- 6 lesions were applied. The total procedure time averaged 4 +/- 1 hours. Fluoroscopy time was 41 +/- 25 minutes. Except for transient AV block in 1 patient, no other complications occurred. Over 12 +/- 8 months, a total of 7 patients (13%) had recurrence of AVNRT, and 6 of them underwent successful repeat slow pathway RF ablation. Recurrence rate was 9% (2 patients) for group 1, with persistent jump or echo beats, and 16% (5 patients) for group 2, without residual slow pathway conduction (P = NS). Five of the recurrences (71%) were noted in group A and 2 in group B. Thus, the recurrence rate was 36% for group A (5 of 14 patients), with posterior ablations, and 5% for group B (2 of 41 patients), with anterior sites of successful RF ablation (P < .05). CONCLUSIONS: After successful RF ablation of the slow pathway in patients with AVNRT, residual slow pathway conduction does not correlate with clinical tachycardia recurrences. However, the site of successful RF ablation of the slow pathway does correlate with arrhythmia recurrences. More recurrences are observed when the site is located inferoposteriorly, at or below the os of the coronary sinus, as compared with medial and anterior locations of the ablation site. PMID- 7994826 TI - Analysis of junctional ectopy during radiofrequency ablation of the slow pathway in patients with atrioventricular nodal reentrant tachycardia. AB - BACKGROUND: Junctional ectopy may occur during radiofrequency (RF) catheter ablation of the slow pathway in patients with atrioventricular nodal reentrant tachycardia (AVNRT). The purpose of the present study was to characterize this junctional ectopy quantitatively. METHODS AND RESULTS: The subjects of this study were 52 consecutive patients with AVNRT who underwent slow pathway ablation and 5 additional patients included retrospectively because they had developed high degree atrioventricular (AV) block during the procedure. A combined anatomic and electrogram mapping approach was used for slow pathway ablation, and AVNRT was successfully eliminated in all patients. In the group of 52 consecutive patients, the incidence of junctional ectopy was significantly higher during 52 effective applications of RF energy than during 366 ineffective applications (100% versus 65%, P < .001). Compared with ineffective RF energy applications, successful RF energy applications had a significantly longer duration of individual bursts of junctional ectopy (7.1 +/- 7.1 versus 5.0 +/- 7.0 seconds [+/- SD], P < .05), a greater total number of junctional beats during the applications (24 +/- 16 versus 15 +/- 8, P < .01), and a greater total span of time during which junctional ectopy occurred (19 +/- 15 versus 11 +/- 12 seconds, P < .01). Four of the 52 patients plus an additional 5 patients developed transient AV block lasting 34 +/- 37 seconds. In 1 of the 9 patients who had transient AV block, third-degree AV nodal block requiring a permanent pacemaker recurred 2 weeks later. In each of the 9 patients who developed AV block, there was ventriculoatrial (VA) block in association with junctional ectopy during the RF energy application immediately preceding the AV block. Among 48 patients who did not develop AV block, 17 patients had at least one episode of VA block during junctional ectopy. The positive predictive value of VA block during junctional ectopy for the development of AV block was 19% in the consecutive series of 52 patients. Among 31 patients who always had 1:1 VA conduction in association with junctional ectopy, 12 had poor VA conduction in the baseline state, with a VA block cycle length of at least 500 milliseconds during ventricular pacing. CONCLUSIONS: In patients with AVNRT undergoing slow pathway ablation, junctional ectopy during the application of RF energy is a sensitive but nonspecific marker of successful ablation. The bursts of junctional ectopy are significantly longer at effective target sites than at ineffective sites. VA conduction should be expected during the junctional ectopy that accompanies slow pathway ablation, even when there is poor VA conduction during baseline ventricular pacing. VA block during junctional ectopy is a harbinger of AV block in patients undergoing RF ablation of the slow pathway. If energy applications are discontinued as soon as VA block occurs, the risk of AV block may be markedly reduced. PMID- 7994827 TI - Results and efficiency of programmed ventricular stimulation with four extrastimuli compared with one, two, and three extrastimuli. AB - BACKGROUND: Conventional programmed ventricular stimulation protocols are inefficient compared with more recently proposed protocols. The purpose of the present study was to determine if additional efficiency could be derived from a 6 step programmed ventricular stimulation protocol that exclusively uses four extrastimuli. METHODS AND RESULTS: The subjects were 209 consecutive patients with coronary artery disease and documented sustained monomorphic ventricular tachycardia, nonsustained ventricular tachycardia, aborted sudden death, or syncope. These patients underwent 159 electrophysiological tests in the absence of antiarrhythmic drug therapy and 105 electrophysiological tests in the presence of antiarrhythmic therapy. Programmed stimulation was performed with two protocols in random order in each patient. Both protocols used an eight-beat drive train, 4-s intertrain pause, and basic drive cycle lengths of 350, 400, and 600 ms. The 6-step protocol started with coupling intervals of 290, 280, 270, and 260 ms, which were shortened simultaneously in 10-ms steps until S2 was refractory. The 18-step protocol used one, two and three extrastimuli in conventional sequential fashion. The end points were 30 s of sustained monomorphic ventricular tachycardia, two episodes of polymorphic ventricular tachycardia requiring cardioversion, or completion of the protocol at two right ventricular sites. There was no significant difference in the yield of sustained monomorphic ventricular tachycardia using the two protocols, regardless of the clinical presentation or treatment with antiarrhythmic drugs. Polymorphic ventricular tachycardia occurred with the 18-step protocol twice as frequently as with the 6-step protocol (6% versus 3%, P < .001). The duration of the 18-step protocol was significantly longer than that of the 6-step protocol in patients with inducible ventricular tachycardia (5.5 +/- 7 versus 2.3 +/- 2 minutes, P < .001), as well as in patients without inducible ventricular tachycardia (25.4 +/- 7 versus 6.9 +/- 2 minutes, P < .001). CONCLUSION: A stimulation protocol that exclusively uses four extrastimuli improves the specificity and efficiency of programmed ventricular stimulation without compromising the yield of monomorphic ventricular tachycardia in patients with coronary artery disease. PMID- 7994829 TI - Interaction of baseline characteristics with the hazard of encainide, flecainide, and moricizine therapy in patients with myocardial infarction. A possible explanation for increased mortality in the Cardiac Arrhythmia Suppression Trial (CAST). AB - BACKGROUND: The Cardiac Arrhythmia Suppression Trial (CAST) was designed to test the hypothesis that suppression of ventricular ectopy with antiarrhythmic drugs after a myocardial infarction reduces the incidence of sudden arrhythmic death. Patients in whom ventricular ectopy could be suppressed with encainide, flecainide, or moricizine were randomly assigned to receive either active drug or placebo. The encainide and flecainide arms of the study were discontinued in 1989 (CAST-I) and the moricizine arm in 1991 (CAST-II) because of excess mortality. To explore the mechanisms of these adverse outcomes, we examined the interaction of baseline characteristics with the hazard of therapy with encainide, flecainide, or moricizine compared with their respective placebos. METHODS AND RESULTS: CAST I comprised 755 patients assigned to flecainide or encainide and 743 patients assigned to placebo, whereas in CAST-II, 502 patients received moricizine and 491 patients received placebo. Clinical and laboratory baseline variables of patients receiving active drug and those receiving placebo were similar. In CAST-I patients, there was a significant interaction of active therapy with both all cause death/cardiac arrest and arrhythmic death/cardiac arrest for non-Q-wave myocardial infarction (total mortality hazard ratios, 1.8 versus 7.9 for Q-wave versus non-Q-wave infarction, P = .03). Ventricular premature depolarization (VPD) frequency > or = 50/h and heart rate > or = 74 beats per minute each interacted significantly with total mortality/cardiac arrest only. In the sicker CAST-II patients (ejection fraction < or = 40%), only diuretic use at baseline interacted significantly with moricizine use for both all-cause death/cardiac arrest and arrhythmic death/cardiac arrest (total mortality hazard ratios, 1.9 versus 0.7 for diuretic use versus no use, P = .01). CONCLUSIONS: Although active treatment in CAST-I was associated with greater mortality than placebo with respect to almost all baseline variables, the therapeutic hazard was more than expected in patients with non-Q-wave myocardial infarction and (for total mortality) frequent premature VPDs and higher heart rates, suggesting that the adverse effect of encainide or flecainide therapy is greater when ischemic and electrical instability are present. The relative hazard of therapy with moricizine in the sicker CAST-II population was greater in those using diuretics. Thus, although these drugs have the common ability to suppress ventricular ectopy after myocardial infarction, their detrimental effects on survival may be mediated by different mechanisms in different populations, emphasizing the complex, poorly understood hazards associated with antiarrhythmic drug treatment. PMID- 7994828 TI - Nonthoracotomy- versus thoracotomy-implantable defibrillators. Intention-to-treat comparison of clinical outcomes. AB - BACKGROUND: Nonthoracotomy-implantable cardioverter/defibrillator (ICD) systems may represent a significant advance in the treatment of patients with life threatening ventricular arrhythmias, but their merits relative to those of the well-established thoracotomy systems remain largely unknown. The objective of this study was to compare the short- and long-term clinical outcomes after attempted ICD implantation via a nonthoracotomy versus thoracotomy approach in similar groups of patients. METHODS AND RESULTS: Between September 1990 and December 1992, 212 consecutive patients underwent attempted ICD system implantation without concomitant cardiac surgery at a single institution. Approach selection was not randomized but rather was based primarily on hardware availability. Primary comparisons of short- and long-term outcome were performed according to the "intention-to-treat" principle. Implantation was attempted via a nonthoracotomy approach in 120 patients (57%) and via a thoracotomy approach in 92 patients (43%). Prior cardiac surgery was more prevalent in the nonthoracotomy patients; otherwise, groups did not differ significantly in terms of prognostically relevant clinical characteristics. Nonthoracotomy implantation was successful in 101 patients (84%). After crossover to thoracotomy implantation (14 patients), the eventual success rate for ICD system implantation was 96% in the nonthoracotomy group. Thoracotomy implantation was successful in 89 patients (97%). Operative mortality was 3.3% in the nonthoracotomy and 4.3% in the thoracotomy groups (P = .73). Nonthoracotomy group patients were less likely to experience postoperative congestive heart failure (6% versus 16%; P = .02) or supraventricular arrhythmia (6% versus 18%; P = .004) and had significantly shorter postoperative intensive care and total hospitalization. Total hospital costs were significantly lower in the nonthoracotomy group ($32,205 versus $37,265; P = .001). After a follow-up of 16 +/- 9 months, there were 17 deaths in the nonthoracotomy group (none sudden) and 12 deaths in the thoracotomy group (1 sudden). One- and 2-year Kaplan-Meier survival probabilities were .87 (95% CI, .78 to .91) and .80 (95% CI, .68 to .88) in the nonthoracotomy group and .90 (95% CI, .82 to .95) and .87 (95% CI, .77 to .93) in the thoracotomy group (P = .56; log-rank test). CONCLUSIONS: Nonthoracotomy ICD implantation is associated with reduced surgical morbidity, postoperative hospital care requirement, and hospital costs and has similar efficacy in preventing sudden death relative to the thoracotomy approach. From these nonrandomized data, it appears that a nonthoracotomy approach should be considered preferable in most patients requiring ICD therapy. PMID- 7994830 TI - Contribution of endothelium-derived nitric oxide to exercise-induced vasodilation. AB - BACKGROUND: Endothelium-derived nitric oxide is an important modulator of resting vascular tone in animals and humans. However, the contribution of nitric oxide to exercise-induced vasodilation is unknown. METHODS AND RESULTS: The effect of NG monomethyl-L-arginine (L-NMMA), an inhibitor of nitric oxide synthesis, on exercise-induced vasodilation was studied in 18 healthy subjects (mean +/- SD, 40 +/- 10 years; 10 women). Acetylcholine was used to test the efficacy of L-NMMA in inhibiting stimulation of nitric oxide synthesis and sodium nitroprusside to test the specificity of L-NMMA in inhibiting endothelium-dependent vasodilation. Intermittent handgrip exercise and infusions of acetylcholine and sodium nitroprusside were performed during intra-arterial infusion of 5% dextrose (control) and L-NMMA (4 to 16 mumol/min). Forearm blood flow was determined by strain-gauge plethysmography. Forearm oxygen extraction was measured from arterial and venous oxygen saturations. In a separate study, 10 subjects performed exercise during infusions of 5% dextrose, L-arginine (the substrate for nitric oxide production), and D-arginine (the stereoisomer that is not a substrate for nitric oxide production). L-NMMA reduced exercise blood flow by 7 +/- 13% (P = .04), increased exercise resistance by 18 +/- 20% (P = .02), and increased exercise oxygen extraction by 16 +/- 17% (P < .001). The degree of inhibition of acetylcholine-induced vasodilation with L-NMMA correlated positively with the degree of reduction in exercise blood flow (r = .55, P = .02). The highest dose of L-NMMA (16 mumol/min) produced the greatest effect; exercise blood flow was reduced by 11 +/- 14% (P = .03), and vascular resistance increased by 26 +/- 23% (P = .005). L-NMMA did not affect the forearm vasodilation produced by sodium nitroprusside. Exercise blood flow, resistance, and oxygen extraction were not significantly modified by infusions of either L- or D-arginine. CONCLUSIONS: Inhibition of nitric oxide synthesis reduces exercise induced vasodilation in the human forearm, indicating that nitric oxide plays a role in exercise-induced vasodilation. Increased availability of nitric oxide substrate does not enhance exercise-induced vasodilation in healthy subjects. These findings have important implications for disease states in which endothelium-derived nitric oxide production is impaired. PMID- 7994831 TI - Abnormal atrial natriuretic peptide and renal responses to saline infusion in nonmodulating essential hypertensive patients. AB - BACKGROUND: Nonmodulation seems to represent an inheritable trait characterized by abnormal angiotensin-mediated control of aldosterone release and renal blood supply and salt-sensitive hypertension. Recently, we demonstrated that atrial natriuretic peptide (ANP) response to angiotensin II also is altered in nonmodulators. Moreover, an abnormal ANP response to acute volume expansion has been shown by others in hypertensive patients displaying some features of nonmodulators. These data induced us to hypothesize that nonmodulators. These data induced us to hypothesize that nonmodulation could be characterized by an abnormal ANP response to saline load. METHODS AND RESULTS: Forty-three essential hypertensive men were subdivided into low-renin patients (n = 12), nonmodulators (n = 15), and modulators (n = 16) according to their renin profile and ability to modulate aldosterone and p-aminohippurate clearance responses to a graded angiotensin II infusion (1.0 ng.kg-1.min-1 and 3.0 ng.kg-1.min-1 for 30 minutes each) on both a low- (10 mmol Na+ per day) and a high- (210 mmol Na+ per day) Na+ intake. The intravenous saline load (0.25 mL.kg-1.min-1 for 2 hours) performed on a low-Na+ diet increased plasma ANP levels in low-renin (from 14.30 +/- 4.68 to 23.30 +/- 7.52 fmol/mL at 120 minutes, P < .05) and modulating patients (from 10.95 +/- 3.55 to 18.21 +/- 5.42 fmol/mL at 120 minutes, P < .05), whereas it did not change the hormone levels in nonmodulators (from 10.77 +/- 3.25 to 13.83 +/- 5.70 fmol/mL at 120 minutes, P = NS). When patients switched from a low- to a high-NaCl diet, plasma ANP levels increased significantly in all groups. However, when the saline load was repeated on a high-NaCl intake, ANP levels increased in both low-renin and modulating patients (P < .05), whereas it failed to increase in nonmodulators. CONCLUSIONS: Nonmodulating hypertensive patients showed a reduced ANP response to saline infusion in the presence of a normal increase of plasma ANP with dietary NaCl load. The impaired ANP response to saline infusion could be due to a different distribution of volume load and contribute to determining the reduced ability to excrete sodium that is commonly described in nonmodulators. PMID- 7994832 TI - Relation between physical training and ambulatory blood pressure in stage I hypertensive subjects. Results of the HARVEST Trial. Hypertension and Ambulatory Recording Venetia Study. AB - BACKGROUND: This study was undertaken to assess whether ambulatory blood pressure (BP) in a population of stage I hypertensive individuals was lower in the subjects performing regular exercise training. METHODS AND RESULTS: The study was carried out in 796 young hypertensive patients (592 men) who had never been treated who took part in the HARVEST trial. The diagnosis of stage I hypertension was made on the basis of six office BP measurements. Subjects underwent noninvasive 24-hour ambulatory BP monitoring, 24-hour urine collection for catecholamine assessment, and echocardiography (n = 457). They were classified as exercisers if they reported at least one session of aerobic sports per week and as nonexercisers if they did not engage regularly in sports activities. Age (P < .0001), body mass index (P = .002), 24-hour heart rate (P < .0001), alcohol intake (P = .02), smoking (P = .02), and norepinephrine output (P = .04) were lower in the active (n = 153) than the inactive (n = 439) men. Physically active men exhibited a lower 24-hour and daytime diastolic BP than the inactive men, while there were no group differences in office BP or in nighttime diastolic BP and in ambulatory systolic BP. The between-group ambulatory diastolic BP difference remained statistically significant after adjustment for age, body mass index, alcohol intake, and smoking (P < .0001). Of the nonexercisers, 46.2% were confirmed hypertensives, compared with only 26.8% of the exercisers (P < .0001), on the basis of daytime diastolic BP. Echocardiographic left ventricular dimensional and functional indexes were similar in the two groups of men. Similar findings were shown by the 16 women who engaged in aerobic sports. CONCLUSIONS: These data suggest that participation in aerobic sports may attenuate the risk of hypertension in young subjects whose office BP is in the stage I hypertensive range at office measurement. PMID- 7994833 TI - Different effects of strenuous exercise and moderate exercise on platelet function in men. AB - BACKGROUND: Platelets play an important role in the pathogenesis of cardiovascular diseases. It is also noticed that on one hand, regular exercise can reduce the risk of cardiovascular diseases, and on the other hand, vigorous exercise provokes sudden cardiac death. We therefore hypothesize that various intensities of exercise may affect platelet function differently. METHODS AND RESULTS: Strenuous and moderate exercise (about 50% to 55% of peak oxygen consumption, VO2peak) on a bicycle ergometer in 10 sedentary and 10 physically active healthy young men was executed on two separate occasions. Blood samples were collected before and immediately after exercise. A newly designed tapered parallel plate chamber was used to assess platelet adhesiveness. Platelet aggregation induced by ADP was evaluated by the percentage of reduction in single platelet count. beta-Thromboglobulin (beta-TG) and platelet factor 4 (PF4) were measured by ELISA. In addition, a similar study on 5 patients with stable angina were also conducted. Our results showed that (1) in the sedentary healthy group, platelet adhesiveness and aggregation were increased by strenuous exercise and depressed by moderate exercise; (2) in the active healthy group, platelet adhesiveness and aggregation were enhanced by severe exercise, whereas only aggregation was decreased by moderate exercise; (3) in the patients with stable angina, platelet adhesiveness and aggregation were enhanced by strenuous exercise and adhesiveness was suppressed by moderate exercise; (4) the degree of hemoconcentration induced by acute exercise tended to be related to the severity of exercise in all subjects; and (5) although severe exercise elevated beta-TG and PF4, there were no significant changes in beta-TG, PF4, and the ratio of beta TG to PF4 in healthy subjects after exercise. CONCLUSIONS: It is concluded that platelet adhesiveness and aggregability may be sensitized by strenuous exercise in both healthy subjects and patients with stable angina. In contrast, platelet function can be suppressed significantly by moderate exercise in the healthy and tends to be depressed in patients with stable angina. The former may increase the risk of cardiac arrest and the latter may protect us from cardiovascular diseases. In addition, the effects of acute exercise tend to be more pronounced in the sedentary than in the active. PMID- 7994834 TI - Role of nitric oxide in exercise-induced vasodilation of the forearm. AB - BACKGROUND: We wished to determine the role of NO in exercise-induced metabolic forearm vasodilation. METHODS AND RESULTS: Young healthy volunteers (n = 11) underwent static handgrip exercise (4 to 5 kg, 3 minutes). Forearm blood flow (FBF) measured by strain plethysmography increased from 4.1 +/- 0.7 mL.min-1.100 mL-1 at rest to 9.8 +/- 1.2 mL.min-1.100 mL-1 immediately after exercise and gradually decreased thereafter. Exercise was repeated after intrabrachial artery infusion of NG-monomethyl-L-arginine (L-NMMA) at 4.0 mumol/min for 5 minutes. L NMMA did not alter blood pressure and heart rate. L-NMMA decreased FBF at rest to 2.9 +/- 0.4 mL.min-1.100 mL-1 (P < .01), peak FBF immediately after exercise to 7.2 +/- 0.7 mL.min-1.100 mL-1 (P < .01), and FBF during the mid to late phase of metabolic vasodilation (P < .01). Calculated oxygen consumption during peak exercise was comparable before and after L-NMMA. Intra-arterially infused L arginine (10 mg/min, 5 minutes) reversed the inhibitory effect of L-NMMA. To determine the effect of the decrease in resting FBF on exercise-induced hyperemia, we normalized FBF after exercise by resting FBF. The percent increases in FBF after exercise from resting FBF were similar before and after L-NMMA. Furthermore, we examined the effect of intra-arterially infused angiotensin II on FBF at rest and after exercise (n = 7). Angiotensin II decreased FBF at rest from 3.1 +/- 0.3 to 1.8 +/- 0.3 mL.min-1.100 mL-1 (P < .01), peak FBF after exercise from 8.1 +/- 0.5 to 5.6 +/- 0.5 mL.min-1.100 mL-1 (P < .01), and FBF during the mid to late phase of metabolic vasodilation. The effects of L-NMMA and angiotensin II on FBF at rest and exercise were similar. CONCLUSIONS: Our results suggest that L-NMMA decreased FBF after exercise largely by decreasing resting FBF. These results suggest that NO may not play a significant role in exercise induced metabolic arteriolar vasodilation in the forearm of healthy humans. PMID- 7994835 TI - Surgery for aortic stenosis in elderly patients. A study of surgical risk and predictive factors. AB - BACKGROUND: Aortic stenosis is the most common valvular lesion occurring among elderly patients and has become extremely frequent because of changing demographics in industrialized countries. Surgical risk after the age of 70 has increased. The increasing older age of patients having surgery justifies an analysis of mortality predictive factors. METHODS AND RESULTS: Between 1976 and February 1993, we performed 2871 operations for aortic stenosis. This study concerns 675 patients (278 men and 397 women) who were > or = 75 years old. Mean age was 78.5 +/- 3 years. Associated lesions were found in 226 patients. A bioprosthesis was implanted in 632 patients (93.6%). Concomitant surgical procedures were performed in 133 patients. Surgical mortality was 12.4% (84 deaths). A longitudinal analysis has been carried out over four successive time periods to evaluate population evolution during these 17 years. Statistical analysis was performed on 46 variables. Multivariate analysis found age (P < .0001), left ventricular failure (P < .0001), lack of sinus rhythm (P < .01), and emergency status (P < .02) to be presurgical independent predictive factors of mortality. CONCLUSIONS: Risk-reducing strategy should both favor relatively early surgery to avoid cardiac failure and emergency situations and pay careful attention to the use of myocardial protection and cardiopulmonary bypass. Indications for surgery should remain broad since analysis failed to determine specific high-risk groups to be eliminated, and surgery remains the only treatment for aortic stenosis. PMID- 7994836 TI - End-systolic volume and long-term survival after coronary artery bypass graft surgery in patients with impaired left ventricular function. AB - BACKGROUND: Left ventricular function is the main predictor of long-term survival in patients with coronary artery disease. In patients with impaired left ventricular function after myocardial infarction, end-systolic volume is a better predictor than the global ejection fraction. We analyzed long-term follow-up of patients with impaired left ventricular function undergoing coronary artery bypass graft surgery to evaluate preoperative predictors of survival. METHODS AND RESULTS: Consecutive patients with ejection fractions < or = 40% (n = 193) who had undergone surgical revascularization were followed to assess the predictive value of preoperative baseline characteristics and catheterization findings for long-term survival. Patients were followed for 133 +/- 30.7 months. At the time of surgery, patient age was 56 +/- 7.9 years and 169 patients (87.6%) had a history of previous myocardial infarction. Thirty-one patients (16%) were female. The ejection fraction was 32 +/- 7%, and the end-systolic volume was 147.4 +/- 52.6 mL. One hundred sixty-four patients (84.9%) had three-vessel disease, and 44 (22.8%) had a left main stenosis with > 50% diameter loss. Follow-up was complete in 99%. Fourteen patients died (7.3%) within the first 30 days after surgery. Twelve-month actuarial survival was 86%, 4-year survival was 80%, and 10-year survival was 40%. Predictors of poor long-term survival on multivariate analysis were end-systolic volume index (chi 2 = 14.02, P = .002), number of previous myocardial infarctions (chi 2 = 6.47, P = .001), preoperative stenosis score (chi 2 = 4.97, P = .02), and age at the time of surgery (chi 2 = 4.45, P = .03). CONCLUSIONS: End-systolic volume index is the major predictor of survival after coronary artery bypass graft surgery in patients with impaired left ventricular function. Strategies to prevent ventricular dilatation, such as angiotensin converting enzyme inhibitors, may improve the long-term outcome in these patients. PMID- 7994837 TI - Relation of smoking with carotid artery wall thickness and stenosis in older adults. The Cardiovascular Health Study. The Cardiovascular Health Study (CHS) Collaborative Research Group. AB - BACKGROUND: Cigarette smoking has been associated with increased risk of atherosclerotic diseases in hospital-based studies and in studies of middle-aged populations but not in population-based studies of older adults with and without clinical cardiovascular disease. METHODS AND RESULTS: We investigated the relation of smoking to carotid artery atherosclerotic disease, expressed as intimal-medial wall thickness and arterial lumen narrowing (stenosis) measured by ultrasound. Subjects were 5116 older adults participating in the baseline examination of the Cardiovascular Health Study, a community-based study of cardiovascular diseases in older age. With increased smoking there was significantly greater internal and common carotid wall thickening and internal carotid stenosis: current smokers > former smokers > never-smokers; for instance, the unadjusted percent stenosis was 24%, 20%, and 16%, respectively (P < .0001). A significant dose-response relation was seen with pack-years of smoking. These findings persisted after adjusting for other cardiovascular risk factors and were also confirmed when analyses were restricted to those without prevalent cardiovascular disease. The difference in internal carotid wall thickness between current smokers and nonsmokers was greater than the difference associated with 10 years of age among never-smoking participants (0.39 mm versus 0.31 mm). Among all participants, the prevalence of clinically significant (> or = 50%) internal carotid stenosis increased from 4.4% in never-smokers to 7.3% in former smokers to 9.5% in current smokers (P < .0001). CONCLUSIONS: These findings extend previous reports of a positive relation between smoking and carotid artery disease to a population-based sample of older adults using several different indicators of atherosclerotic disease. PMID- 7994838 TI - HDL cholesterol and mortality in Finnish men with special reference to alcohol intake. AB - BACKGROUND: There is substantial evidence that a low serum level of HDL cholesterol (HDLC) is a risk factor for coronary deaths. However, data on older people are scarce, and previous studies have not examined this association in relation to alcohol intake. METHODS AND RESULTS: Coronary mortality, all-cause mortality, and mortality due to alcohol and violence were related to HDLC levels among 7052 male smokers 50 to 69 years old in south and west Finland enrolled from 1984 to 1988 in the ATBC (AT, alpha-tocopherol; BC, beta-carotene) Study placebo group. During the average follow-up period of 4.7 years, 620 men died; 222 of these deaths were from coronary heart disease and 82 from causes related alcohol and violence. HDLC levels were inversely associated with coronary mortality, irrespective of age, whereas high total cholesterol was positively associated with coronary mortality among the younger men, 50 to 59 years of age, but not among the older men, 60 to 69 years old. Correction for temporal variation in HDLC measurement indicated a 43% stronger inverse association between HDLC and coronary mortality compared with that based only on a single value. The inverse association of HDLC and coronary mortality was less marked at higher levels of alcohol intake. All-cause and alcohol- and violence-related mortality were positively associated with HDLC among the younger men. All-cause mortality showed a U-shaped dose response among men > or = 60 years old. CONCLUSIONS: Previous studies may have underestimated the beneficial effect of high HDLC because of regression-dilution bias and the confounding effect of heavy alcohol intake. This study supports the view that, particularly among older men, lipoprotein fractions may be more appropriate for screening than total cholesterol. PMID- 7994839 TI - Role of arterial chemoreceptors in mediating the effects of endogenous adenosine on sympathetic nerve activity. AB - BACKGROUND: Exogenous adenosine has been shown to increase muscle sympathetic nerve activity (MSNA), blood pressure, heart rate, and ventilation in conscious humans, effects attributed to peripheral chemoreceptor activation. METHODS AND RESULTS: To determine whether endogenous adenosine has similar effects and whether they are mediated through chemoreceptor activation, we examined the effects of dipyridamole, an inhibitor of adenosine reuptake, on sympathetic nerve activity and ventilation. Twenty studies were conducted on separate days in 15 healthy volunteers. We examined responses to dipyridamole 0.56 mg/kg during room air breathing (n = 7), during hyperoxia (100% O2, n = 6), and during room air breathing after pretreatment with aminophylline (n = 7). During room air breathing, dipyridamole increased MSNA from 231 +/- 42 to 504 +/- 136 U/min, heart rate from 65 +/- 3.8 to 96 +/- 4.7 beats per minute, and systolic blood pressure from 129 +/- 3.5 to 140 +/- 4.8 mm Hg; central venous pressure decreased from 5.5 +/- 0.4 to 4.5 +/- 0.3 mm Hg (P < .01), and minute ventilation increased from 7.8 +/- 0.6 to 9.1 +/- 0.5 L/min (P < .01). During peripheral chemoreceptor suppression (with hyperoxia), there was a dissociation of the effects of dipyridamole on ventilation and sympathoexcitation. Effects on ventilation were attenuated, but sympathoexcitatory effects were not. Pretreatment with aminophylline, an adenosine receptor antagonist, either abolished (blood pressure, minute ventilation, and end-tidal CO2) or markedly attenuated (MSNA and heart rate) the effects of dipyridamole during room air breathing. CONCLUSIONS: Augmentation of endogenous adenosine with dipyridamole increases sympathetic nerve activity and ventilation in conscious humans. The ventilatory effects of endogenous adenosine are mediated predominantly by chemoreceptor activation, but the sympathetic and hemodynamic responses to endogenous adenosine are probably mediated by an additional afferent mechanism that is independent of peripheral chemoreceptor activation. PMID- 7994840 TI - Magnetic resonance and echocardiographic imaging of pulmonary artery size throughout stages of Fontan reconstruction. AB - BACKGROUND: Because pulmonary artery size is considered by most investigators to be a major prognosticator of outcome in patients undergoing staged Fontan reconstruction, the objective of the present study was to determine the efficacy of noninvasive measures in determining pulmonary artery size. METHODS AND RESULTS: This study analyzed the T1-weighted, spin-echo magnetic resonance and echocardiographic images of 36 functional single-ventricle patients throughout stages of Fontan reconstruction (prebidirectional and postbidirectional cavopulmonary anastomosis and after Fontan) and compared them with angiography images at cardiac catheterization. Magnetic resonance imaging had a high degree of agreement with angiography, with the McGoon index agreeing better than the Nakata index and absolute right and left pulmonary diameters. Although echocardiography had fair agreement with angiography, it agreed less well and had a wider standard deviation than magnetic resonance imaging for all indexes and measurements and, based on the prediction interval, would be a poorer prospective measure of pulmonary artery size in this population. In addition, echocardiography was a poorer measure of pulmonary artery size as the size of the vessel increases. Magnetic resonance imaging correctly detected five of five patients with nonconfluent branch pulmonary arteries and six of six patients with stenoses, whereas echocardiography was unable to visualize any of the patients with nonconfluent branch pulmonary arteries with certainty and only two of six (33%) with stenoses. CONCLUSIONS: Magnetic resonance imaging is a useful, noninvasive tool to determine pulmonary artery size in patients undergoing Fontan reconstruction and is superior to echocardiography. Echocardiography was a fair predictor of pulmonary artery size, but magnetic resonance imaging agreed with angiography better than echocardiography and outperformed echocardiography in diagnosing branch pulmonary artery discontinuity and stenoses. Magnetic resonance imaging may avoid unnecessary cardiac catheterization, especially in older patients, and may obviate the need for jugular or subclavian catheterization in those who have undergone bidirectional cavopulmonary anastomosis. PMID- 7994841 TI - Diagnosis in adolescents and adults with congenital heart disease. Prospective assessment of individual and combined roles of magnetic resonance imaging and transesophageal echocardiography. AB - BACKGROUND: The inability to obtain complete diagnoses with transthoracic echocardiography in many adults with congenital heart disease provided the incentive to evaluate prospectively the individual and combined roles of magnetic resonance imaging (MRI) and transesophageal echocardiography (TEE) as "second line" techniques for unresolved diagnostic problems. METHODS AND RESULTS: Eighty five patients were studied; 81 had MRI with a 0.5-T magnet to obtain spin-echo images, cine-MRI, and flow-velocity maps. Seventy-nine patients had TEE (37 biplane). A simple score (range, 0 to 1) was used for quantification of the results of MRI and TEE alone, for their comparison (in the 75 patients who had both), and for assessment of their combination. MRI, TEE, or their combination achieved a score of at least 0.75 in 18 of 25 diagnostic categories. A summary of the scores showed that for intracardiac anatomy. MRI scored 0.34, TEE scored 0.71 (P < .0001), and MRI plus TEE scored 0.84 (P < .003); for extracardiac anatomy, MRI scored 0.76, TEE scored 0.23 (P < .0001), and MRI plus TEE scored 0.84 (P = NS); and for hemodynamics and function, MRI scored 0.58, TEE scored 0.41 (P < .05), and MRI plus TEE scored 0.67 (P = NS). Total scores were MRI, 0.52; TEE, 0.50 (P = NS); and MRI plus TEE, 0.80 (P < .0001). MRI and TEE were inadequate for collateral and coronary arteries and pulmonary vascular resistance. Cine-MRI and flow-velocity maps comprised 43% of the MRI scores. Biplane TEE was better than single plane (scores of 0.59 versus 0.42, P < .0001). CONCLUSIONS: MRI and TEE are important and complementary "second-line" investigations for congenital heart disease. Analysis of their performance in a wide range of diagnostic categories provides guidelines for their judicious application. Where both are available, diagnostic catheterizations are either obviated or simplified. PMID- 7994842 TI - Plasma thromboxane B2 concentration in pulmonary hypertension associated with congenital heart disease. AB - BACKGROUND: We investigated the plasma concentration of thromboxane B2 (TXB2), a stable metabolite of thromboxane A2 (TXA2), to assess platelet activation in 78 patients who had pulmonary hypertension associated with congenital heart disease (PH group) and 16 patients with almost normal hemodynamics (control group). METHODS AND RESULTS: The PH group was divided into two subgroups: pulmonary vascular resistance (Rp) < or = 10 U/m2 (Rp < or = 10 group) and > 10 U/m2 (Rp > 10 group). In addition, the Rp < or = 10 group was divided on the basis of clinical symptoms into groups with dyspnea (dyspnea[+] group) and without dyspnea (dyspnea[-] group). Plasma TXB2 levels were measured by radioimmunoassay. Plasma TXB2 levels in the three groups (control, Rp < or = 10, and Rp > 10) were significantly different (P < .005); the TXB2 levels in the Rp < or = 10 group were significantly higher than the others. Among the Rp < or = 10 patients, the plasma TXB2 levels were significantly higher in the dyspnea(+) group than in the dyspnea(-) group (P < .0001). In addition, the pulmonary-to-systemic flow ratio and pulmonary blood flow divided by body surface area were significantly higher in the dyspnea(+) group than in the dyspnea(-) group (P < .02 and P < .002, respectively). CONCLUSIONS: These findings suggest that platelet activation led to increased TXA2 release in patients with pulmonary hypertension, especially those with dyspnea and Rp < or = 10. TXA2 release from platelets probably caused constriction of the pulmonary arterioles and the bronchi, thus worsening pulmonary hypertension and dyspnea in these patients. In the patients with high Rp values, it was considered that the number of pulmonary arterioles where platelets could be activated had been reduced. PMID- 7994843 TI - Low-dose, beta-particle emission from 'stent' wire results in complete, localized inhibition of smooth muscle cell proliferation. AB - BACKGROUND: Restenosis after catheter-based revascularization has been demonstrated to be primarily caused by medial and/or intimal smooth muscle cell (SMC) proliferation. The objective of this study was investigate the ability of local emission of beta-particles from a 32P-impregnated titanium "stent" wire source to inhibit vascular SMC and endothelial cell proliferation in cell culture and to determine the dose-response characteristics of this inhibition. METHODS AND RESULTS: A series of experiments were performed using 0.20-mm-diameter titanium wires that were impregnated with varying low concentrations of 32P (activity range, 0.002 to 0.06 microCi/cm wire, n = 47) or 31P (nonradioactive control, n = 28) in cultures of rat and human aortic SMCs and in cultured bovine aortic endothelial cells. The zone of complete cell growth inhibition (in millimeters from stent wire) was measured using light microscopy in the cultures exposed to the radioactive (32P) or control (31P) wires at 6 and 12 days after plating. In both rat and human SMC cultures there was a distinct 5.5- to 10.6-mm zone of complete SMC inhibition at wire activity levels > or = 0.006 microCi/cm. In contrast, there was no zone of inhibition surrounding the control (31P impregnated) wires (P < .001 versus 32P wires at all wire activities > or = 0.006 microCi/cm for human and rat SMCs). Proliferating bovine endothelial cells were more radioresistant than SMCs, with no zone of inhibition observed at wire activity levels up to 0.019 microCi/cm (P < .001 versus SMCs at 0.006 microCi/cm and 0.019 microCi/cm). CONCLUSIONS: We conclude that very low doses of beta particle emission from a 32P-impregnated stent wire (activity levels as low as 0.006 microCi/cm of wire) completely inhibit the growth and migration of both rat and human SMCs within a range of 5.5 to 10.6 mm from the wire. Endothelial cells appear to be much more radioresistant than SMCs. These data suggest that an intra arterial stent impregnated with a low concentration of 32P may have a salutary effect on the restenosis process. Whether this approach can be used successfully and safely to inhibit restenosis in vivo and in the clinical setting is under investigation. PMID- 7994844 TI - Reduction in reperfusion-induced myocardial necrosis in dogs by RheothRx injection (poloxamer 188 N.F.), a hemorheological agent that alters neutrophil function. AB - BACKGROUND: Reperfusion after prolonged coronary artery occlusion may be followed by additional myocardial necrosis persisting for hours to days. Potential mechanisms include neutrophil-mediated injury and compromised flow within the microcirculation of the reperfused myocardium. Poloxamer 188 is a nonionic surfactant with beneficial hemorheological and neutrophil-inhibitory properties. The purpose of the present study was to determine if poloxamer 188 is capable of reducing the myocardial injury associated with sustained reperfusion and to examine the effect of treatment duration. METHODS AND RESULTS: Three groups of closed-chest dogs underwent 90 minutes of left anterior descending coronary artery occlusion (angioplasty balloon) and 72 hours of reperfusion. Poloxamer 188, formulated as RheothRx Injection (Burroughs Wellcome Co), was given as a 75 mg/kg IV bolus 15 minutes before reperfusion followed by a 150 mg.kg-1.h-1 continuous IV infusion for 4 hours (n = 13) or 48 hours (n = 13); control dogs (n = 12) received saline for 48 hours. The 48-hour infusion of poloxamer 188 resulted in a 42% reduction in infarct size (as a percent of the area at risk) compared with the control group (25.0 +/- 4.2% versus 43.3 +/- 4.3%, P D .01), whereas the 4-hour group demonstrated a 25% reduction in infarct size compared with the control group (32.4 +/- 4.3%, P = .08). ANCOVA demonstrated that the 48 hour infusion of poloxamer 188 reduced myocardial infarct size independent of differences in collateral blood flow (P = .002 versus control). A trend toward infarct size reduction was observed in the 4-hour infusion group (P = .098 versus control by ANCOVA). Plasma creatine phosphokinase concentration was lower in both poloxamer 188-treated groups (P < .05 versus control). Global left ventricular ejection fraction at 72 hours of reperfusion was improved in the 48-hour infusion group compared with the control group (43 +/- 3.1% versus 33 +/- 2.0%, P < .05), whereas ejection fraction in the 4-hour group was 37 +/- 1.3% (P = NS versus control). Regional ventricular function was also significantly better in the 48 hour infusion group compared with the control group. In vitro studies demonstrated that at concentrations comparable to those achieved in vivo, poloxamer 188 inhibited neutrophil chemotaxis. This finding may represent a beneficial mechanism of action. CONCLUSIONS: A 48-hour infusion of poloxamer 188 reduced myocardial infarct size and improved left ventricular function in this dog model of 90 minutes of coronary artery occlusion and 72 hours of reperfusion. The finding that the 4-hour infusion of poloxamer 188 did not result in similar benefits suggests that additional reperfusion injury occurred between 4 and 48 hours. PMID- 7994845 TI - Abolition of cyclic flow variations in stenosed, endothelium-injured coronary arteries in nonhuman primates with a peptide fragment (VCL) derived from human plasma von Willebrand factor-glycoprotein Ib binding domain. AB - BACKGROUND: Platelets play an important role in the pathophysiology of acute coronary syndromes. The interaction between the platelet glycoprotein Ib receptor and von Willebrand factor is a critical event allowing platelet adhesion and aggregation and subsequent thrombus formation in vessels with high shear rates and damaged endothelium. Therefore, we tested the hypotheses that VCL, an antagonist of von Willebrand-glycoprotein Ib binding domain, (1) attenuates/abolishes cyclic flow variations in stenosed, endothelium-injured coronary arteries in nonhuman primates and (2) reduces botrocetin-induced platelet aggregation in vitro after intravenous in vivo administration. METHODS AND RESULTS: Cyclic flow variations were established in anesthetized, open-chest baboons (n = 18). The baboons were divided into three groups. One group (n = 8) received a bolus of VCL (4 mg/kg IV) followed by an infusion (6 mg.kg-1.h-1) for 90 minutes (schedule A). Another group (n = 6) received a 2-mg/kg bolus followed by an infusion of 3 mg.kg-1.h-1 for 90 minutes (schedule B). The third group received a placebo infusion of normal saline. Under dosing schedule A, cyclic flow variations were abolished in 7 of 8 baboons after 33 +/- 18 minutes and markedly attenuated in 1. The frequency of cyclic flow variations fell from 18 +/ 9.4 per hour during the control period to 1 +/- 2.5 per hour after VCL infusion, P < .002. After cessation of infusion, cyclic flow variations remained abolished in 5 of 7 animals for > 3 hours and returned in 2 of 7 after 2 to 2.5 hours. Under schedule B, cyclic flow variations were abolished in 3 of 6 baboons and markedly reduced in the remainder. The number of cyclic flow variations fell from 17 +/- 4.8 per hour during the control period to 5 +/- 4.9 per hour after the VCL infusion, P < .001. The cyclic flow variations returned spontaneously at 38 +/- 40 minutes under this dosing schedule. Placebo infusion of saline had no effect on cyclic flow frequency or severity. VCL administration was associated with slight prolongation in bleeding time and a reduction in botrocetin-induced platelet aggregation. The bleeding time increased from a control time of 88 +/- 32 to 276 +/- 204 seconds, P < .03, and from 142 +/- 28 to 176 +/- 36 seconds, P = .056, for schedules A and B, respectively. VCL decreased platelet aggregation in response to botrocetin (20 micrograms/mL), from a control value of 66 +/- 30.3 to 33 +/- 31.3 omega, P < .05, and from 64 +/- 23.5 to 46 +/- 15.8 omega, P = .006, for dosing schedules A and B, respectively. CONCLUSIONS: Therefore, administration of a peptide fragment corresponding to von Willebrand-glycoprotein Ib binding domain (1) is effective in abolishing cyclic flow variations in stenosed, endothelium-injured coronary arteries and (2) reduces platelet aggregation in vivo in response to botrocetin in nonhuman primates. PMID- 7994846 TI - Anterior septal coronary artery infarction in the canine: a model of ventricular tachycardia with a subendocardial origin. Ablation and activation sequence mapping. AB - BACKGROUND: In humans, chronic ventricular tachycardia (VT) is usually associated with myocardial infarcts that involve the interventricular septum. In an effort to more closely mimic the anatomic substrate that gives rise to chronic VT in humans, we developed a canine model of VT in which the anterior septal coronary artery was ligated. The site of earliest activation, the subsequent activation sequence, and the mechanism of VT associated with the resultant ventricular septal infarct was then evaluated to determine if this model accurately reflected the characteristics of human VT. METHODS AND RESULTS: Seventeen dogs underwent occlusion-reperfusion ventricular septal infarcts. Four to 7 days later, electrophysiological studies were performed. VT was initiated by programmed electrical stimulation and terminated by pacing at a cycle length of 50% to 75% of the VT cycle length. Electrophysiological studies were performed using a 256 channel mapping system. A total of 15 VT morphologies were mapped in 9 animals. Fourteen of 15 morphologies had septal subendocardial sites of earliest activation and 1 had a septal midwall site of earliest activation. VT ablation was performed using a nitrous oxide cryoprobe and confirmed the site of earliest activation by subsequently rendering VT noninducible. Electrophysiological studies demonstrated four distinct VT activation sequences: (1) circular reentrant (n = 7), (2) concentric spread (n = 5), (3) figure-of-eight (n = 2), and (4) septal midwall (n = 1). CONCLUSIONS: This canine model of ventricular septal infarction produces VTs with sites of earliest activation and activation sequences similar to those in humans. A reentrant mechanism as the basis of these arrhythmias is supported by the following observations: (1) all VT was initiated and terminated with programmed electrical stimulation; (2) VT activation sequences were consistent with reentry; and (3) precise interruption of the sequence terminated the VT and rendered it noninducible. PMID- 7994847 TI - Adenosine receptor involvement in a delayed phase of myocardial protection 24 hours after ischemic preconditioning. AB - BACKGROUND: We previously reported a delayed phase of protection against infarction 24 hours after ischemic preconditioning in the rabbit. In the present study, we investigated the possibility that this "second window of protection," like the well-described early phase of protection in the rabbit, might be associated with adenosine receptor activation. METHODS AND RESULTS: In the first series of experiments, we examined whether adenosine receptor blockade with 8-(p sulfophenyl)-theophylline (SPT) during preconditioning could abolish the delayed protection against infarction 24 hours later. Open-chest rabbits were subjected to myocardial preconditioning (PC) with the four 5-minute coronary occlusions or they were sham operated on (SHAM). During these procedures, animals received either SPT (PC + SPT, n = 6; and SHAM + SPT, n = 6) or vehicle (PC + VEH, n = 12; and SHAM + VEH, n = 11). Twenty-four hours later, infarct development after a 30 minute coronary occlusion/120-minute reperfusion insult was assessed with triphenyltetrazolium staining. In vehicle-treated rabbits, the infarct-to-risk ratio (I/R) was reduced from 53.6 +/- 5.7% (SHAM + VEH) to 32.9 +/- 4.6% (PC + VEH) (P < .05), clearly indicating a delayed phase of protection. Although I/R was not significantly different between SHAM + VEH (53.6 +/- 5.7%) and SHAM + SPT (61.7 +/- 5.4%), in PC + SPT the delayed protection was abolished (I/R = 56.8 +/- 3.8%). In the second series of experiments, we examined if pharmacological adenosine A1 receptor stimulation could evoke a delayed phase of protection. Conscious rabbits were pretreated with intravenous boluses of saline or the A1 receptor-selective agonist 2-chloro-N6-cyclopentyladenosine (CCPA), and infarct size in response to 30-minute ischemia/120-minute reperfusion was assessed 24 hours later. I/R was 54.5 +/- 2.7% in saline-pretreated controls (n = 12). Pretreatment with 25 micrograms/kg CCPA (n = 6), 50 micrograms/kg CCPA (n = 6), or 100 micrograms/kg CCPA (n = 6) resulted in I/R ratios of 37.1 +/- 4.2% (P < .01), 37.7 +/- 2.2% (P < .01), and 26.3 +/- 5.7% (P < .01), respectively. In both series of experiments, there were no differences in systemic hemodynamics during the infarct protocol, assessed as rate-pressure product, between the different experimental groups. CONCLUSIONS: Twenty-four hours after repetitive brief coronary occlusions, susceptibility to infarction in rabbit myocardium is reduced, an effect that may have clinical relevance. Results of the present study suggest that this second window of protection following preconditioning may, like the early phase of protection, be initiated by an adenosine-related mechanism. PMID- 7994848 TI - Geometric remodeling is not the principal pathogenetic process in restenosis after balloon angioplasty. Evidence from correlative angiographic histomorphometric studies of atherosclerotic arteries in rabbits. AB - BACKGROUND: Restenosis after balloon angioplasty of coronary arteries is thought to be a proliferative response of the arterial wall to injury. Recently, it has been suggested that geometric remodeling of the arterial wall, rather than intimal fibromuscular hyperplasia, may be the major pathophysiological mechanism underlying restenosis. In this study, we evaluated the relative contribution of a geometric decrease in arterial size versus neointimal growth to luminal narrowing associated with restenosis after balloon angioplasty of atherosclerotic femoral arteries in rabbits. METHODS AND RESULTS: Focal femoral atherosclerosis was induced by endothelial desiccation injury followed by a 2% cholesterol diet. After 1 month on the high cholesterol diet, the animals were subjected to one of four strategies: (1) balloon angioplasty, (2) balloon angioplasty followed by treatment with the factor Xa inhibitor antistasin, (3) combined laser and balloon angioplasty, or (4) no angioplasty. Animals were killed 2 hours or 28 days after angioplasty, and excised femoral artery segments were prepared for histomorphometric analysis. Angiography was performed serially before and immediately after angioplasty and before the animals were killed. An initial postprocedural gain in luminal diameter at sites of angioplasty was followed by a significant reduction in diameter by angiography and a significant increase in luminal cross-sectional area narrowing by plaque by histomorphometry 28 days after angioplasty compared to adjacent nonangioplastied segments of the same arteries, to nonangioplastied control arteries, or to angioplastied segments of animals treated with the factor Xa inhibitor antistasin. By contrast, the overall arterial size (cross-sectional area bounded by the external elastic lamina) at sites of restenosis was not significantly different from adjacent nonangioplastied segments in the majority of arteries excised at 28 days, and the mean overall arterial size at sites of restenosis was not significantly different from corresponding segments of nonangioplastied control arteries or from angioplastied segments of animals treated with antistasin. In the minority of angioplastied arteries in which the arterial size did change, most got larger. CONCLUSIONS: Geometric remodeling resulting in a decrease in overall cross sectional arterial size does not appear to be the principal pathogenetic mechanism for restenosis after balloon angioplasty with or without laser in this experimental model. PMID- 7994849 TI - Marked activation delay caused by ischemia initiated after regional K+ elevation in in situ pig hearts. AB - BACKGROUND: Conduction mediated by the slow inward (Ca2+) current occurs in vitro under specific experimental conditions but has not been documented in ventricular muscle in vivo during regional myocardial ischemia, perhaps because certain constituents of ischemia (including hypoxia and acidosis) may inhibit the Ca2+ current in this setting. We hypothesized that slow conduction mediated by the Ca2+ current could occur during acute ischemia in situations in which the extracellular K+ rise was more marked relative to the degree of acidosis, as may occur at ischemic boundaries. METHODS AND RESULTS: In open-chest, anesthetized swine, an arterial shunt from the carotid artery to the mid-left anterior descending coronary artery was created through which a solution of KCl was infused to raise extracellular K+ ([K+]e) to approximately 9.4 mmol/L before the initiation of ischemia, which we termed "K(+)-modified ischemia." Ischemia initiated at a normal [K+]e ("unmodified ischemia") resulted in a mean activation delay in the center of the ischemic zone of 55 +/- 26 milliseconds after 5 minutes of ischemia and a decrease in epicardial longitudinal conduction velocity from 53 to 21 cm/s before the onset of conduction block. K(+)-modified ischemia resulted in a mean activation delay in the center of the ischemic zone of 181 +/- 8 milliseconds and a decrease in epicardial longitudinal conduction to less than 10 cm/s. K(+)-modified ischemia was associated with ventricular fibrillation in 85% of episodes compared with 28% of episodes of unmodified ischemia (P < .01). Verapamil prevented the occurrence of marked activation delay during K(+) modified ischemia, producing local activation block following a maximum activation delay of 74 +/- 25 milliseconds. In two experiments, responses mediated by the slow inward current were produced by regional K+ elevation to 15 to 16 mmol/L, followed by concomitant regional administration of epinephrine (10( 7) mol/L). Regional [K+]e elevation alone to this level resulted in local activation block following a maximum activity delay of 70 to 80 milliseconds, whereas administration of epinephrine in combination with high [K+]e resulted in return of local activation with an activation delay of 160 to 180 milliseconds (ie, similar to that during K(+)-modified ischemia). CONCLUSIONS: Compared with unmodified ischemia, K(+)-modified ischemia resulted in marked activation delay and a high incidence of ventricular fibrillation. Based on measurements of longitudinal conduction velocity, the inhibitory effect of verapamil, and the results of experiments with high [K+]e plus epinephrine, we conclude that the marked activation delay during K(+)-modified ischemia represents conduction mediated by the slow inward current. Because the conditions produced by K(+) modified ischemia (high [K+]e with minimal acidosis) are similar to conditions in and near ischemic border regions, we hypothesize that responses mediated by the slow inward current may occur in such regions during unmodified ischemia and may participate in the development of reentrant arrhythmias. PMID- 7994850 TI - Cyclosporine impairs release of endothelium-derived relaxing factors in epicardial and resistance coronary arteries. AB - BACKGROUND: Cyclosporin A is reported to impair endothelium-mediated vasorelaxation and induce endothelin release in some noncoronary vascular beds. We wished to determine whether acute cyclosporine administration induces endothelial dysfunction in coronary conductance or resistance arteries. METHODS AND RESULTS: We examined the effect of intracoronary acetylcholine, N omega-nitro L-arginine methyl ester (L-NAME), L-arginine, nitroglycerin, and adenosine before and after acute cyclosporine administration (3 mg/kg IV over 30 minutes) in anesthetized dogs. Flow velocity was measured with a 0.014-in Doppler wire to assess resistance vessel responses, and epicardial coronary lumen area was simultaneously measured with a 4.3F, 30-MHz imaging catheter inserted over the Doppler wire. In 6 dogs, acetylcholine-induced increase in flow velocity was attenuated by cyclosporine in vehicle (137% to 55% at 10(-5) mol/L, P < .001), as was acetylcholine-induced epicardial vasodilation (14.1% to 6.7% at 10(-5) mol/L, P < .001). Vasodilation in response to intracoronary nitroglycerin (200 micrograms) and adenosine (6 mg) were unchanged by cyclosporine. Epicardial vasoconstriction with L-NAME (10(-4) mol/L) was reduced by cyclosporine (Pre, 7.4 +/- 0.9%; Post, 2.6 +/- 1.2%; P = .04), but L-arginine (10(-4) mol/L) had no effect after cyclosporine. In another 5 dogs, pure cyclosporine impaired acetylcholine-induced vasodilatation to the same degree as cyclosporine in vehicle (Cremophor); vehicle infusion did not impair endothelial function. In 5 more dogs, cyclosporine did not increase either arterial or coronary sinus concentrations of endothelin-1. CONCLUSIONS: The present study shows that cyclosporine acutely impairs release of endothelium-derived relaxing factor in canine conductance and resistance coronary arteries and provides evidence for decreased epicardial nitric oxide release after cyclosporine. The potential contribution of acute cyclosporine-induced coronary endothelial dysfunction to posttransplant vasculopathy needs further study. PMID- 7994851 TI - Effect of chronic dihydropyridine (isradipine) on the large arterial walls of spontaneously hypertensive rats. AB - BACKGROUND: The effect of genetic hypertension and of chronic therapy by calcium entry blocker (CEB, isradipine) on the function and structure of large arteries has been studied in adult spontaneously hypertensive rats (SHR, n = 30) and in their normotensive control Wistar-Kyoto (WKY) rats (n = 30). METHODS AND RESULTS: Fifteen-week-old rats were randomly allocated to treatment with isradipine (3 mg/kg subcutaneously once a day) or to placebo and followed for 12 weeks. Hemodynamic parameters, including instantaneous pressure and aortic velocity, were recorded under anesthesia at the end of the treatment period. Passive mechanical properties of carotid arteries were measured in situ in the presence or the absence of smooth muscle cell activity (potassium cyanide poisoning). Histomorphometric parameters of the carotid and aortic media, including cross sectional area, medial thickness, nucleus density and size, and medial contents of proteins of interstitial matrix, were measured by an automated morphometric system. Untreated SHRs had greater peripheral resistance, stiffer and thicker arterial walls because of smooth muscle cell hyperplasia (thoracic aorta and carotid artery) and/or hypertrophy (thoracic aorta), and increased collagen content than did normotensive control rats. SHRs showed a significant left ventricular hypertrophy. For the whole duration of treatment, treatment with CEB normalized the arterial pressure in SHRs. We observed a significant decrease in peripheral resistance, increased cardiac output, and left ventricular contractility without significant reduction in left ventricular hypertrophy. Increases in diuresis and natriuresis were associated during the last week of treatment in both treated strains with marked increase in plasma renin activity; in contrast, urinary aldosterone was increased by treatment in WKY rats but not in SHRs. Arterial compliance was significantly increased by CEB under control and passive conditions. CEB induced a significant reduction in the medial hypertrophy of the aortic walls of SHRs and WKY rats associated with a reduction in medial hyperplasia. In the carotid artery, CEB reduced smooth muscle cell hypertrophy but did not affect the smooth muscle cell hyperplasia. Isradipine significantly reduced the arterial wall collagen contents in both strains, with marked increases in the elastin content in the carotid but not in the aortic wall. CONCLUSIONS: These results suggest that (1) despite normalization of arterial pressure, chronic treatment with CEB in SHRs does not significantly reduce left ventricular hypertrophy, probably because of increase in myocardial contractility and/or increase in plasma renin activity; (2) mechanical properties of the arterial wall are normalized by treatment; and (3) remodeling of the arterial wall by CEB is not uniform according to the studied vessel. PMID- 7994853 TI - Effect of exercise on left ventricular mechanical efficiency in conscious dogs. AB - BACKGROUND: We studied the effect of exercise (7.2 to 8.0 km/h) on the efficiency of the conversion of metabolic energy to external work or stroke work (SW) by the left ventricle (LV). METHODS AND RESULTS: Energy use was calculated from LV myocardial oxygen consumption per beat (MVO2). LV volume was calculated from orthogonal dimensions and coronary flow measured with ultrasonic flow probes. The total mechanical energy of the LV was calculated as the pressure-volume area (PVA). At rest, the MVO2-PVA point fell on the MVO2-PVA relation determined by steady-state changes in arterial pressure produced by graded infusions of phenylephrine. Exercise increased the slope (Ees) of LV end-systolic pressure volume (PV) relation by 29%. During exercise, the MVO2-PVA point shifted to the right only slightly above the control MVO2-PVA relation by 0.007 +/- 0.005 mL O2.beat-1.100 g LV-1. Despite the increase in ventricular contractility with exercise, the PVA/MVO2 ratio was unchanged because of the marked increase in PVA. During exercise, the transmission of total mechanical energy to external work (SW/PVA) increased from 65 +/- 5% to 72 +/- 4% (P < .01) as the ratio of the arterial end-systolic elastance to Ees decreased from 1.1 +/- 0.2 to 0.8 +/- 0.1 (P < .05). Thus, LV mechanical efficiency (SW/MVO2 = SW/PVA.PVA/MVO2) improved from 12.9 +/- 1.5% to 14.3 +/- 1.1% (P < .05) during exercise. CONCLUSIONS: Exercise increases the efficiency of conversion of metabolic energy to external work by the LV due to alteration in LV arterial coupling resulting in increased production of mechanical energy and enhanced transmission of mechanical energy to external work, which more than offsets any increased metabolic cost of the enhanced contractility. PMID- 7994852 TI - Relative effects of alpha 1-adrenoceptor blockade, converting enzyme inhibitor therapy, and angiotensin II subtype 1 receptor blockade on ventricular remodeling in the dog. AB - BACKGROUND: Progressive ventricular remodeling after myocardial damage is associated with a poor prognosis. Optimal prevention of the histopathological processes involved in remodeling requires a more complete understanding of the mechanisms involved in initiating and maintaining these structural changes. Since the sympathetic nervous system and the renin-angiotensin system may be involved in the remodeling process, the structural effects of pharmacological inhibitors have been evaluated in a canine model of localized myocardial injury resulting from transmyocardial DC shock. METHODS AND RESULTS: The study is comprised of two protocols run in series. In protocol 1, zofenopril (Z), a converting enzyme inhibitor (CEI), prevented the increase in left ventricular mass (LVM) and end diastolic volume (LVV) observed in the control group (C) at 16 weeks (Z: LVM, 69.8 +/- 3.4 to 65.4 +/- 2.6 g, P = NS; LVV, 45.4 +/- 2.7 to 51.6 +/- 2.7 mL, P = NS; C: LVM, 68.4 +/- 3.2 to 91.4 +/- 2.9 g, P = .0001; LVV, 56.6 +/- 3.0 to 71.9 +/- 2.4 mL, P = .0003). Terazosin, an alpha 1-adrenoceptor antagonist, failed to prevent remodeling at 16 weeks despite continued receptor blockade. In protocol 2, the antiremodeling effect of full-dose CEI therapy with ramipril was confirmed. Low-dose ramipril that exerted no hemodynamic effect failed to prevent remodeling (LVM, 89.7 +/- 4.6 to 105.7 +/- 3.4 g, P = .01; LVV, 61.8 +/- 3.8 to 76.8 +/- 3.3 mL, P = .002). An angiotensin II subtype 1 receptor blocker also failed to prevent the increase in LVM or LVV (LVM, 89.0 +/- 4.6 to 109.7 +/- 5.3 g, P = .0001; LVV, 66.0 +/- 1.9 to 78.4 +/- 3.6 mL, P = .007). CONCLUSIONS: High dose CEI therapy can prevent progressive structural changes resulting from localized myocardial damage induced by DC shock. the failure of alpha 1 adrenoceptor blockade and angiotensin II subtype 1 blockade to attenuate remodeling argues against an important direct role for norepinephrine acting through alpha 1-receptors or angiotensin II acting through the type 1 receptor in the remodeling process in this model. PMID- 7994854 TI - Timing and velocity of ejection as major determinants of end-systolic pressure in isolated rabbit hearts. AB - BACKGROUND: Systolic shortening is known to produce muscle deactivation. The present study was designed to analyze whether the velocity and the timing of ejection play a role on end-systolic pressure-volume relations (ESPVR). METHODS AND RESULTS: In isolated rabbit hearts, left ventricular pressure and volume were recorded and digitized, and left ventricular volume was controlled by a servosystem (4-millisecond cycles) to alter the timing of ejection. A significant deficit in end-systolic pressure was observed when ejection was late in systole with respect to earlier ejection. This was associated with a significantly reduced end-systolic elastance. End-systolic pressure of beats with slow ejection was intermediate between that of the beats with early ejection and that of beats with late ejection with a significantly increased end-systolic volume compared with beats with early rapid ejection. The same results were obtained with hypertrophied hearts (abdominal aortic stenosis). Pressure-volume loop areas were significantly increased in beats with slow ejections and with rapid delayed ejections versus early rapid ejections. No change in the positive peak of dP/dt was observed when the timing and the velocity of ejection were modified. CONCLUSIONS: ESPVR is modified by the ejection profile, with a decreased end systolic pressure and an increased pressure-volume loop area related to the velocity and the amount of shortening during the end-systolic phase. These indices of ventricular function thus must be used with caution when the timing of ejection is altered, and the end-diastolic volume-peak dP/dt relation may be a better index of ventricular function. PMID- 7994855 TI - Effect of ventilation on resuscitation in an animal model of cardiac arrest. AB - BACKGROUND: The need for ventilation during the initial management of cardiac arrest is an important public health problem that is being debated. The present study was designed to determine whether ventilation affects return of spontaneous circulation from cardiac arrest in a swine model with an interval of untreated ventricular fibrillation of 6 minutes, as reported in witnessed out-of-hospital human cardiac arrest. METHODS AND RESULTS: Twenty-four animals were randomly assigned to two groups: one that received ventilation during the first 10 minutes of chest compression and one that did not. Coronary perfusion pressure and minute ventilation were continuously recorded. Arterial and mixed venous blood gases were measured at intervals. Return of spontaneous circulation was defined prospectively as an aortic systolic blood pressure of > 80 mm Hg for > 5 minutes and was the primary outcome variable. All animals were anesthetized, paralyzed, and intubated. Ventricular fibrillation was induced and persisted for 6 minutes without chest compression, followed by mechanical chest compression for 10 minutes and then attempted defibrillation. Animals without return of spontaneous circulation were given epinephrine, ventilation, and chest compression for an additional 3 minutes. Defibrillation was again attempted, and animals were assessed for return of spontaneous circulation. There were no significant differences between the two groups in baseline prearrest mean cardiac index, coronary perfusion pressure, or arterial and mixed venous blood gases. However, after 9 minutes of chest compression, significant differences were noted between the ventilated and nonventilated groups. The nonventilated group had significantly (P < .05) lower mean arterial PO2 (38 +/- 17 mm Hg compared with 216 +/- 104 mm Hg) and higher PCO2 (62 +/- 16 mm Hg compared with 35 +/- 8 mm Hg), lower mixed venous PO2 (15 +/- 7 mm Hg compared with 60 +/- 7 mm Hg). Nine of 12 (75%) of the ventilated animals, and only 1 of 12 (8%) of the nonventilated animals had return of spontaneous circulation after cardiac arrest (P < .002). CONCLUSIONS: In this animal model of cardiac arrest, ventilation was important for resuscitation. The importance of ventilation could be related to the prolonged duration of untreated ventricular fibrillation and the significantly greater hypoxia and hypercarbic acidosis found in the nonventilated animals. PMID- 7994856 TI - Observations of ventilation during resuscitation in a canine model. AB - BACKGROUND: Fear of infection limits the willingness of laymen to do cardiopulmonary resuscitation (CPR). This study assessed the time course of change in arterial blood gases during resuscitation with only chest compression (no ventilation) in an effort to identify the time for which ventilation could be deferred. METHODS AND RESULTS: Aortic pressures and arterial blood gases were monitored in seven 20- to 30-kg dogs in ventricular fibrillation (VF) at 2-minute intervals during chest compression alone (no ventilation) at 80 to 100 compressions per minute. Before the induction of ventricular fibrillation, all animals were intubated and ventilated with room air, 10 mL/kg. The endotracheal tube was removed when VF was induced. Pre-VF arterial pH, PCO2, and O2 saturation were (mean +/- SEM) 7.39 +/- 0.02, 27.0 +/- 1.5 mm Hg, and 97.5 +/- 0.5%, respectively, with aortic pressures being 143.2 +/- 5.7/116.2 +/- 4.6 mm Hg. At 4 minutes of chest compression alone, the corresponding values were 7.39 +/- 0.03, 24.3 +/- 3.1 mm Hg, and 93.9 +/- 3.0%, with an arterial pressure of 48.1 +/- 7.7/22.6 +/- 3.9 mm Hg. Mean minute ventilation during the fourth minute of CPR, measured with a face mask-pneumotachometer, was 5.2 +/- 1.1 L/min. CONCLUSIONS: These data suggest that in the dog model of witnessed arrest, chest compression alone during CPR can maintain adequate gas exchange to sustain O2 saturation > 90% for > 4 minutes. The need for immediate ventilation during witnessed arrest should be reexamined. PMID- 7994857 TI - Effect of myocardial fiber direction on epicardial potentials. AB - BACKGROUND: Understanding the relations between the architecture of myocardial fibers, the spread of excitation, and the associated ECG signals is necessary for addressing the forward problem of electrocardiography, that is, predicting intracardiac and extracardiac ECGs from known intracardiac activity. So far, these relations have been studied experimentally only in small myocardial areas. In this study, we tested the hypothesis that potential distributions measured over extensive epicardial regions during paced beats reflect the direction of superficial and intramural fibers through which excitation is spreading in both the initial and later stages of ventricular excitation. We also tried to establish whether the features of the epicardial potential distribution that correlate with fiber direction vary as a function of pacing site, intramural pacing depth, and time elapsed after the stimulus. An additional purpose was to compare measured epicardial potentials with recently published numerical simulations depicting the three-dimensional spread of excitation in the heart muscle and the associated potential fields. METHODS AND RESULTS: The hearts of 18 mongrel dogs were exposed and 182 to 744 unipolar electrograms were recorded from epicardial electrode arrays (2.3 x 3.0 to 6.5 x 6.5 cm). Hearts were paced at various intramural depths through an intramural needle. The overall number of pacing sites in 18 dogs was 241. Epicardial potential distributions, electrographic waveforms, and excitation time maps were displayed, and fiber directions in the ventricular wall underlying the electrodes were determined histologically. During the early stages of ventricular excitation, the position of the epicardial maxima and minima revealed the orientation of myocardial fibers near the pacing site in all cases of epicardial and intramural pacing and in 60% of cases of endocardial or subendocardial pacing. During later stages of propagation, the rotation and expansion of the positive areas correlated with the helical spread of excitation through intramurally rotating fibers. Marked asymmetry of potential patterns probably reflected epicardial-endocardial obliqueness of intramural fibers. Multiple maxima appeared in the expanding positive areas. CONCLUSIONS: For 93% of pacing sites, results verified our hypothesis that epicardial potential patterns elicited by ventricular pacing reflect the direction of fibers through which excitation is spreading during both the initial and later stages of propagation. Epicardial potential distributions provided information on the site of origin and subsequent helical spread of excitation in an epicardial-endocardial, endocardial-epicardial, or double direction. Results were in agreement with previously published numerical simulations except for the asymmetry and fragmentation of the positive areas. PMID- 7994858 TI - Suppression of thrombolysis in a canine model of pulmonary embolism. AB - BACKGROUND: The brisk fibrinolytic response of canines has impaired efforts to develop a canine model of chronic thromboembolic pulmonary hypertension. Difficulties in retaining chronic embolic residuals were partially overcome by administration of tranexamic acid (TXA) (Circulation. 1991;83:1272-1279.). In this study, we used type 1 plasminogen activator inhibitor (PAI-1), a major inhibitor of the endogenous fibrinolytic system, to determine its efficacy in the suppression of thrombolysis in canines. METHODS AND RESULTS: Thrombus was induced in the inferior vena cava of anesthetized mongrel dogs with thrombin and a special double-balloon catheter; 2 hours later, the thrombus was embolized. In one group of dogs, activated type 1 plasminogen activator inhibitor (PAI-1) (130 micrograms) was delivered directly into the forming thrombus; in another, TXA (110 mg/kg) was given intravenously before thrombus formation; in controls, thrombus was induced without inhibitors. Cross-linked fibrin degradation product (D-dimer) appeared in the blood of control animals within 1 hour of thrombus induction (176 +/- 62.5 versus 1.02 +/- 0.39 ng/mL baseline; mean +/- SEM), was maximal by 4 hours (413 +/- 110 ng/mL) and remained elevated at 24 hours (90.8 +/ 19.5 ng/mL). Compared with controls, PAI-1 and TXA suppressed D-dimer release by 80% and 85%, respectively, over the first 24 hours. One week later, animals were killed, and residual emboli were harvested. Perfusion scan defects persisted in all animals at this time, but there were no scan defect differences among groups. However, emboli recovered from animals receiving PAI-1 still harbored immunoreactive PAI-1 and were, on average, more than twofold greater in mass (393 +/- 56 mg) than emboli recovered from either controls (183 +/- 76 mg) or animals receiving TXA (180 +/- 80 mg). CONCLUSIONS: Intravenous TXA and intrathrombus PAI 1 effectively suppress thrombolysis for 24 hours in canines. Thromboemboli enriched with PAI-1 appear to resist lysis for longer periods of time (up to 1 week). These findings are consistent with the hypothesis that PAI-1 remains associated with the embolus, where it continues to inhibit lysis, whereas TXA eventually diffuses out of the embolus, allowing lysis to ensue. PMID- 7994859 TI - Survival and predictors of survival in patients with congestive heart failure due to Chagas' cardiomyopathy. AB - BACKGROUND: The fundamental determinant of the natural history of Chagas' disease is cardiac involvement. METHODS AND RESULTS: We studied 104 male patients with congestive heart failure due to Chagas' disease to estimate the survival distribution function and to evaluate age, functional class (FC), maximal oxygen consumption (VO2max), and ejection fraction (EF) as predictors of survival. Statistical evaluation was performed through univariate (Student's t test and chi 2 test) and multivariate analyses (Cox's regression model). Overall survival was 66% at 1 year, 56% at 3 years, and 48% at 5 years. Ages were not statistically different (P = .9811) between survivor (40.3 +/- 8.7) and nonsurvivor (40.3 +/- 9.4) groups. The ejection fraction(s) were statistically different (P = .0001) between survival (43.6 +/- 9.9) and nonsurvival (30.6 +/- 8.1) groups, as was VO2max (P = .0001) (21.0 +/- 4.7 and 15.0 +/- 4.9, respectively). Most of the surviving patients were in FC II and most of the nonsurvivors were in FC IV (P = .0001). VO2max (P = .0001) and EF (P = .0008) are highly associated with survival time in the multivariate analysis, but FC (P = .0578) is less important. Age (P = .9811) did not influence survival. CONCLUSIONS: We conclude that 50% of the patients with heart failure due to Chagas' disease die in 47 months and that VO2max and EF are important indices of survival in this group. PMID- 7994861 TI - Decompensated diabetes. New features of an old problem. PMID- 7994860 TI - Value of physical signs in the diagnosis of ventricular tachycardia. AB - BACKGROUND: Although the use of physical signs for the diagnosis of ventricular tachycardia (VT) was described in the early 1900s, their value in this role has never been systematically assessed. METHODS AND RESULTS: Using a blinded, randomized protocol, we examined the ability of 26 clinicians to detect ventriculoatrial (VA) dissociation during cardiac pacing in 21 patients with both atrial and ventricular pacing wires in situ after successful ablation of accessory pathways. In protocol 1 (10 patients), pacing was randomized to either ventricular pacing alone (simulating VT) or to atrioventricular sequential pacing (simulating supraventricular tachycardia or VT with intact VA conduction) at rates of 150 or 180 beats per minute. Each patients was examined by four clinicians blinded to the pacing mode. Clinicians were asked to make a diagnosis of "VA association" or "VA dissociation" after examining the patient for variability of the arterial pulse, jugular venous pulse (JVP), and first heart sound. In protocol 2 (11 patients), randomization of pacing mode was performed between examination of each of the three physical signs so that the value of each sign was assessed individually. In protocol 1, a diagnosis of VA dissociation (VT) was made in 21 of 40 observations, with a specificity of 75%, sensitivity of 70%, and a positive predictive value (PPV) of 71%. In protocol 2, from a total of 132 observations (44 for each sign), the sensitivity, specificity, and PPV for a diagnosis of VT were as follows: arterial pulse, 61%, 71%, 70%; JVP, 96%, 75%, 82%; and first heart sound, 58%, 100%, 100%. CONCLUSIONS: It is concluded that, in patients with a regular tachycardia of uncertain origin, clinically detectable variations in the first heart sound and JVP are highly specific and sensitive indicators, respectively, of a diagnosis of VT. Assessment of the arterial pulse is of little value in this role. PMID- 7994862 TI - Images in cardiovascular medicine. Cardiac rhabdomyomas in tuberous sclerosis (Bourneville's disease). PMID- 7994863 TI - The prognostic significance of nonsustained ventricular tachycardia in hypertrophic cardiomyopathy. PMID- 7994864 TI - The French paradox: vegetables or wine. PMID- 7994865 TI - Thromboembolism after negative TEE. PMID- 7994866 TI - Exclusion of atrial thrombus by transesophageal echocardiography does not preclude embolism after cardioversion of atrial fibrillation. PMID- 7994867 TI - Identification of coronary artery stenoses and poststenotic blood flow patterns using a miniature high-frequency epicardial transducer. PMID- 7994868 TI - Optimal risk factor management in the patient after coronary revascularization. A statement for healthcare professionals from an American Heart Association Writing Group. PMID- 7994869 TI - Chromosomal abnormalities detected after an abnormal ultrasound in pregnancy. AB - Improvements in ultrasound technology have resulted in an increasing number of requests for prenatal chromosome testing because of fetal abnormalities detected in utero. Between January 1990--January 1991, 388 tissue samples were referred to our laboratory for cytogenetic analysis, of which 202 were amniotic fluids samples, 157 chorionic villus biopsies and 29 fetal blood specimens. Of these 54 were referred for fetal abnormalities detected prenatally on high resolution ultrasound. Chromosomal analysis was successful in 50 cases, and included 6 (12%) chromosomally abnormal fetuses: 2 trisomy 21, 2 trisomy 18, one 45,X and one unbalanced translocation. The maternal age for three of the four cases of autosomal trisomy were below 35 years (the cut-off for amniocentesis for advanced maternal age). In contrast, 273 prenatal chromosome studies performed for advanced maternal age (AMA) produced only 4 (1.5%) chromosomally abnormal fetuses. These abnormalities detected on ultrasound indicate a significant population of fetal chromosomal aberrations which would otherwise not be detected prenatally. PMID- 7994870 TI - Two cases of ovarian cysts in postmenopausal patients under antiestrogen treatment. AB - In 20% of premenopausal breast cancer women on Tamoxifen (TAM) treatment there is an ovarian enlargement: in literature one case of acutely cystic ovaries is described. We observed 2 cases of acutely cystic ovaries in postmenopausal women surgically treated during a long-term adjuvant therapy with TAM. PMID- 7994871 TI - The role of laparoscopy in the treatment of endometriosis. AB - The aim of the present study was to evaluate the role of laparoscopy not only in the diagnosis but also in the therapy of pelvic endometriosis. Ninety-four patients underwent laparoscopy between May 1991 and May 1993. The patients were divided into 2 groups, according to the indication for laparoscopy: group I (benign ovarian cysts n = 47); group II (chronic pelvic pain, n = 47). All laparoscopies were performed by 2 surgeons only. When present, endometriosis was scored according to the American Fertility Society revised classification 1985 (AFS 1985). Endometriosis was present in 37 (39.4%) of the 94 patients included in the study: 19 out of 47 (40.4%) in group I, 18 out of 47 (38.3%) in group II. In 29 patients with endometriosis (78.3%), the score was reduced surgically during the diagnostic procedure. In 24 cases (82.8%) by laparoscopy and in 5 cases (17.2%) only, by laparotomy. Therefore, the careful selection of cases, the use of appropriate instruments and the experience in endoscopic surgery, combined with a good knowledge of pelvic anatomy, may allow the treatment of endometriosis immediately after diagnosis by laparoscopy, resulting in shorter hospitalization, less physical trauma, and a lower number of post-operative adhesions. PMID- 7994872 TI - Gestosis and fetal rejection: immunopathogenetic role of HLA-DR. AB - In this study we faced the problem of etiopathogenesis of EPH Gestosis, focusing our attention on the role of immunitary aspects in determining its onset. We typed HLA-DR in 20 couples with gestosic patient and in 20 control couples. Blood samples were taken into heparin-treated test tubes, from all the couples and HLA typed through standard lymphotoxicity technique in accordance with Terasaky (1). Our results in couples with a gestosic patient, showed homozygosis in 65% of patients and in 70% of partners; in 35% of cases homozygosis was present in both partners, and these were the most severe cases. It is also worth mentioning that in all the couples with gestosic patient, at least one of the partners resulted homozygotic. Homozygosis would therefore represent a predisposing factor in the etiopathogenesis of gestosis, and pre-conception HLA-DR typing of the couple could prove to be a valid alarm signal for gestosis risk. PMID- 7994873 TI - AIDS in Italy and proposals for a new therapeutic strategy. AB - In Italy, the number of AIDS cases reported up to September 1993 was 18,832. Of these, 3,544 were women (21%), mainly of fertile age. AIDS in pregnancy has aroused great interest in Italy, mainly due to the extent of the phenomenon, which is not equalled in other Western countries. In this contribution to the study of HIV infection in pregnancy, the Authors propose a new procedure for monitoring, asymptomatic HIV-positive pregnant women, using fetal Fibronectin as an indicator of aspecific chorionamnionitis and the threat of premature birth, both considered as a risk factors for transmission of the virus from mother to child. PMID- 7994875 TI - A rare case of IUD tubal migration. Case report. AB - The Authors describe a rare case of IUD tubal migration. The uterine device had been inserted twelve years before. A hysteroscopical removal of the IUD was tried unsuccessfully, because it was impossible to locate it either in the uterine cavity or at the fallopian tube orifice level. The patient underwent a minilaparotomy and the IUD was found out at the peritubal level. An ecographic control of all intrauterine devices insertions is recommended. PMID- 7994874 TI - Ovarian fibro-thecoma in a 19 years old Sudanese girl. Gynaecological case report. AB - An unmarried, 19 years old, Sudanese girl developed a firm right ovarian mass which increased in size to reach a diameter of 25 x 25 cm and a weight of 2.8 kg in 8 months time. The patient's condition was associated with amenorrhoea, polycystic ovary and ascites. The ovarian tumour was diagnosed by clinical examination and ultrasound scanning and was identified as a fibrothecoma by histopathology. PMID- 7994876 TI - A voluminous paraovarian cyst. Case report. AB - Paraovarian cysts represent 9-10% of all annexial tumescences. The Authors present a case of voluminous paraovarian cyst in young woman referring abdominal heaviness and swelling for about eight months. During laparotomy a 35 cm cyst with liquid content was revealed. The cystic mass was extirpated preserving the woman's reproductive capacity. PMID- 7994877 TI - The organization of subperitoneal connective tissue in the female pelvis. AB - The organization of the subperitoneal connective tissue in the female pelvis was studied in 6 cases, aged between 58 and 65, deceased from extrapelvic diseases. The pelvic viscera were removed as a whole with the surrounding subperitoneal tissue using a circular cut performed at the level of the pelvic walls. The specimens were fixed in 5% formalin. The bladder dome, uterine body and rectum, up to the anorectal junction, were removed. In two cases the specimens were dehydrated and embedded in paraffin. Ten micron sections were stained with Haematoxilin-Eosin and Azan-Mallory. In 2 other cases the specimens were plastinated according to Von Hagens E12 technique; the passage in acetone at room temperature lasted 24 hours. In the remaining 2 cases the plastination with E12 was carried out after a passage in acetone at room temperature which lasted about 15 days in order to fully remove the lipids from the subperitoneal adipose tissue. The morphological findings demonstrate that the subperitoneal tissue of the female pelvis has an areolar structure with small adipose lobules separated by thin fibrous laminae connected to the vasculo-nervous bundles and to the parietal and visceral layers of the fascia pelvica. The three dimensional spatial organization of the network of thin connective laminae constitutes an anatomical device with possible supporting properties. PMID- 7994878 TI - Persistent vulvovaginal candidiasis: systemic treatment with oral fluconazole. AB - 52 patients affected by persistent vulvovaginal candidiasis underwent systemic therapy with oral Fluconazole at a dose of 150 mg once a week for 3 weeks. 31 (59.61%) patients were cured at the first control after therapy. Of the remaining 21 patients, 4 (7.69%) were lost at follow-up and 17 (32.69%) underwent a second cycle of systemic therapy with complete recovery confirmed at the further controls. The overall percentage of recoveries was equal to 92.30%. The results suggest that Fluconazole is very effective in mycotic vulvovaginitis with irrelevant side effects. PMID- 7994879 TI - Role of goserelin-depot in the clinical management of uterine fibroids. AB - On 30 women suffering from uterine fibroids, the monthly subcutaneous administration of goserelin depot (3.6 mg) for 6 (n = 22) or 12 months (n = 8) induced an about 50% shrinkage of uterus and fibroid volume, and within 3 months, an increase in the haematocrit value, with no metabolic side effects or detectable bone demineralization, evaluated by single photon absortiometry at distal radius. Both uterine and fibroid volumes reversed to pretreatment values after 3 months of goserelin depot withdrawal. In comparison with untreated subjects, on another 10 patients a three month administration of goserelin depot reduced the loss of blood during the surgical removal of the uterus or fibroids. Present data indicate that goserelin depot is effective and relatively safe in the medical management of uterine fibroids. Although, goserelin depot cannot yet be proposed as a definite medical therapy, it may represent a useful instrument in the presurgical management of uterine fibroids. PMID- 7994880 TI - Transvaginal ultrasound versus histology in endometrial hyperplasia. PMID- 7994881 TI - Snoring. PMID- 7994882 TI - A prospective analysis of incidental paranasal sinus abnormalities on CT head scans. AB - A prospective analysis of the incidence of paranasal sinus opacification in 100 patients referred for cranial computerized tomography (CT) for non-sinus related problems is described. The findings were correlated with symptomatic assessment. Twenty-seven per cent of asymptomatic patients had sinus opacification. The study illustrates the importance of careful clinical correlation when interpreting CT scans of the paranasal sinuses. PMID- 7994883 TI - Transantral orbital decompression for Graves' disease. AB - Seventy-five patients with Graves' disease have been treated by transantral orbital decompression. In the first post-operative month the average reduction in proptosis was 3 mm. In the years following the operation this reduction increased to an average of 4.5 mm. In 32% of the patients without diplopia before surgery, the diplopia that developed afterwards did not disappear, 83% of them were successfully treated by extraocular muscle surgery. Seventy per cent of the patients experienced immediate post-operative improvement of visual acuity. Only three patients remained with anaesthesia of the infra-orbital nerve. A total of 65% of the patients found the operation procedure beneficial while 76% were satisfied with the ophthalmological result. We conclude, that transantral orbital decompression, though with moderate morbidity, gives good results in patients with the orbital complications of Graves' disease. PMID- 7994884 TI - Communication, functional disorders and lifestyle changes after total laryngectomy. AB - Functional changes after total laryngectomy, including voice quality, hyposmia and dysgeusia, nasal discharge, swallowing and smoking habits were studied by means of a structured interview with 63 laryngectomized patients. Eighty per cent of the patients reported that they were satisfied with the quality of their voice including speaking on the telephone. Significant correlations were found between the quality of the voice and fatigue, frequency of making telephone calls and anxiety about speaking (P < 0.01). Vocal rehabilitation was achieved in the majority of patients (78%) with the indwelling Provox voice prosthesis. Forty five per cent of the patients complained about annoying eructation. Hyposmia was reported by 52% of the patients, while 15% experienced dysgeusia. A significant correlation was found between hyposmia and dysgeusia (R = 0.43, P < 0.001). All patients with a taste problem also reported a poor sense of smell. Daily nasal discharge was reported by 38% of the patients. Due to difficulties in swallowing solid food, about one quarter of the patients changed their diet. All but one patient had been heavy smokers pre-operatively. Only 9% continued to smoke post operatively. These results, along with the previously reported respiratory problems resulting from total laryngectomy, should be taken into account in counselling patients who are candidates for this surgical procedure. PMID- 7994885 TI - A video-fluoroscopic study of patients treated by diverticulectomy and cricopharyngeal myotomy. AB - Although the short- and long-term results of surgical procedures for treatment of posterior pharyngeal diverticula are well documented, their effect on normal swallowing has not been extensively investigated. The aim of this study was to assess the changes in swallowing that occur after diverticulectomy with cricopharyngeal myotomy. Fifteen patients who underwent surgery in the previous 10 years were interviewed, examined and underwent a video-fluoroscopic barium swallow. Frame to frame analysis of the barium studies showed a multitude of abnormalities, even amongst those who were asymptomatic. Excision of a pharyngeal pouch does not appear to restore a normal swallowing mechanism. PMID- 7994886 TI - Epithelial migration in mastoid cavities. AB - The epithelial migration in 18 dry ears with a cavity after surgery was studied by the ink-dot method and compared with the epithelial migration in 15 normal ears. A qualitatively normal centrifugal migration pattern was observed in all cavity ears. Considerable variation in migration speed was observed within the same cavity ear, thus a comparison with the migration speed in normal ears was impossible. No definite relationship was apparent between migration speed and the self-cleansing ability of the ear, which primarily appeared to be a function of the macroscopic appearance of the cavity (i.e. the presence of pockets or ridges). We conclude that epithelial migration is as important in maintaining the self-cleansing function and non-infected state in cavity ears as it is in normal ears. PMID- 7994887 TI - Bacterial invasion of the tonsillar tissues in acute pharyngotonsillitis and in the adenoid: a preliminary study. AB - In order to understand the immunological and inflammatory processes in which the tonsils are involved it is necessary to know the spatial relation between bacteria and the tissues. In this study four adenoids and four palatine tonsils obtained at elective surgery and four palatine tonsils obtained during a chaud surgery for quinsy were examined histologically. Acridine orange and fluorescence microscopy were used to identify bacteria in tonsillar tissue. The adenoids were also stained with haematoxillin-eosin. Bacteria were in every case seen on the surfaces and in the crypts of the tonsils and adenoids. In the tissues, however, bacteria were never seen irrespective of whether the tonsils were obtained during an acute infection or not. We conclude that bacterial invasion in tonsillar tissue is neither a prerequisite for a clinically manifest acute bacterial pharyngotonsillitis nor a common feature in tonsils clinically recognized as non infected. PMID- 7994888 TI - Bilateral sensorineural hearing loss in members of a maternal lineage with mitochondrial point mutation. AB - Pure-tone audiometry was carried out on members of a recently described maternal lineage with sensorineural deafness, harbouring a novel mitochondrial mutation in the gene for tRNA-ser(UCN). This revealed a characteristic pattern of symmetrical bilateral sensorineural hearing losses in each affected individual, predominantly affecting the high-frequencies, but with considerable variability between individuals. No clear correlation was observed between age and severity, but most subjects reported progressive worsening of their condition. Some members of the lineage were found to be heteroplasmic for the tRNA-ser(UCN) mutation. However, the severity of hearing loss was poorly correlated with the representation of the mutant mtDNA, indicating that other, as yet unidentified factors must be involved in the aetiology of this disorder. PMID- 7994889 TI - Oral squamous cell cancer in non-users of tobacco and alcohol. AB - In a well-defined group of 161 consecutive patients with intra-oral squamous cell carcinoma we found 23 non-users of tobacco and alcohol. The non-users in this prospective study were compared with users of tobacco and alcohol in the study, and to a sex- and age-matched control group drawn at random from the Danish Central Citizenry Registration. The users in the patient group represented a significantly higher number than in the control group. As to non-users, women represented a higher number in the patient group compared with the control group. Among users and non-users differences were found in the location of the primary tumour and in the degree of differentiation of the tumour. Haematological status and liver function parameters were different in the two groups. There was no difference in dental or oral hygiene status or risk occupation among the groups. The stage and the course of the disease (corrected survival) showed only insignificant differences. The non-user group contained especially older women, and only one of them had anaemia. PMID- 7994890 TI - Maternal blood group in otitis media with effusion. AB - Risk factors for otitis media with effusion (OME) have proved difficult to apply in selecting persistent cases, or those otherwise requiring intervention. Explanations may include low predictive values of individual factors and the costs of data collection. In this study, profiles on 225 children from conception to age 7 years were compiled from medical and Health Authority records and structured interviews with parents. On the grounds that nearly all cases receiving medical intervention after waiting and onward referral are more than transitory (although many persistent cases will not receive such attention) this was taken as the dependent variable--a marker of persistence. Established risk factors and maternal blood group A were considered singly to predict intervention, then in combination using logistic regression. Maternal blood group A gave a relative risk (RR) for intervention of 2.82. The noted occurrence of an attack of acute otitis media (AOM) before the first birthday gave a RR of 6.13. When these two factors were used together, the RR climbed steeply to 26.77. These findings suggest that further research is justified into the nature of the influence of blood group A on OME, and the use of combinations of risk factors to give enhanced prediction. PMID- 7994891 TI - Post-operative evaluation of functional endoscopic sinus surgery with computed tomography. AB - Fifty consecutive patients underwent functional endoscopic sinus surgery (FES) for bilateral rhinosinusitis. Pre- and post-operative computerized tomographic scans were evaluated. Of 50 patients, 45 (90%) experienced improvement in symptoms. Post-operative scans gave less encouraging results, with a slightly improved score for the combined group of sinuses and for the ethmoidal and maxillary sinuses separately. The difference between the pre- and post-operative CT score for the ethmoidal sinuses was statistically significant. The frontal sinus showed similar pre- and post-operative radiological findings. For the inexperienced surgeon we recommend computer tomographic examination 4-6 months after surgery. This could prove helpful if recurrence of symptoms occurs. For the experienced surgeon, clinical and endoscopic follow-up for at least 3 years is appropriate. PMID- 7994892 TI - Does adenoidectomy have an adjuvant effect on ventilation tube insertion and thus reduce the need for re-treatment? AB - Two hundred and twenty-two children with bilateral otitis media with effusion were followed for 5 years. A ventilation tube was inserted into one ear only and reinserted if the condition had not resolved. The need for reinsertion in 139 children in whom the adenoids were also removed was compared with the 83 children treated by tube insertion alone. In the combined group in year 1, 91% required one tube compared with 62% treated with only a tube. By year 5, 66% of the combined group required one tube compared with 32.5% in those without adenoidectomy. There was some relationship between tube reinsertion and age, and also with parental smoking. It is possible that the combination of adenoidectomy with tube insertion may prove more cost-effective than tube insertion in selected cases alone. In addition, once adenoidectomy becomes more established as a day case procedure, the cost benefit will be more advantageous in those children treated with adenoidectomy and a tube compared with those treated with only a tube. PMID- 7994893 TI - Diclofenac and post-tonsillectomy haemorrhage. AB - The authors noticed a marked increase in the incidence of reactionary post operative haemorrhage after tonsillectomy during the course of 1992. This increase appeared to be related to the introduction of diclofenac as a post operative analgesic. A retrospective review of casenotes of patients having tonsillectomy under the care of the senior author (P.M.R.) in 1992 revealed that four of the 73 patients (5.5%) receiving diclofenac at induction of anaesthesia suffered reactionary haemorrhage requiring operative control, as compared with two of 293 (0.7%) receiving other analgesics. PMID- 7994894 TI - The mechanism of speech perception in patients with a multichannel cochlear implant. AB - The mechanism of speech perception in patients with a multichannel cochlear implant was investigated by administering vowel, consonant, and speech recognition tests, and comparing sound spectrograms with the activities recorded from the cochlear implant electrodes. Vowel recognition was found to be adequate, but consonant recognition was poor. Although the cochlear hair cells of such patients are known to be functionally damaged, the cochlear nerve was found to have the capacity to characterize frequency. The signals from the implanted device were very simple compared with those from the normal cochlea; however, the patients could nevertheless understand speech well after cochlear implantation. PMID- 7994895 TI - Laser palatoplasty for snoring due to palatal flutter: a further report. AB - The purpose of this paper is to report the longer term results of laser palatoplasty which 1 developed in the early part of 1992. The early results of this procedure were published in the Annals of the Royal College of Surgeons of England and showed that 14 of 16 patients had good snoring control while two did not. Since then a further three patients have relapsed so that five patients out of 16 (34%) must be considered failures. Only a larger series and longer follow up can determine whether or not laser palatoplasty has a place in the management of snoring. PMID- 7994896 TI - Preliminary experiences with microscopic tonsillectomy. AB - Experiences with a modified technique of tonsillectomy are described. The surgery is performed viewing the tonsil through the operating microscope and using the bipolar diathermy forceps for dissection and diathermy of blood vessels. In a pilot-study of 70 patients, the microscopic method was found to be an elegant technique which substantially reduced intra-operative blood loss and did not prolong surgery. Post-operative morbidity will be assessed in a further study. PMID- 7994897 TI - Bipolar diathermy tonsillectomy. AB - Tonsillectomy is an operation performed by various techniques. We have developed a bipolar diathermy dissection technique that allows a low intra-operative blood loss without an increase in complications. The average blood loss was less than 4 ml in 100 patients. Most were able to drink and eat by 4 and 10 hours respectively. There was no increase in analgesic requirements. No primary haemorrhage was recorded; three patients had a secondary haemorrhage. The technique allows accurate coagulation of blood vessel and is an easy procedure to learn. PMID- 7994898 TI - Therapeutic advances in immunosuppression. AB - Immunosuppressive therapy is appropriate for the prevention or reversal of allograft rejection, and for the treatment of autoimmune disorders and allergic disease. Recent advances in our understanding of the cellular and molecular mechanisms that regulate immune responses have paralleled elucidation of the modes of action of a variety of therapeutic immunosuppressive agents, both 'old' and new. These developments have identified potential targets for more refined and specific intervention strategies that are now being tested in the clinic. PMID- 7994899 TI - Allergy to Hevea latex. PMID- 7994900 TI - Anticardiolipin antibodies in HIV infection: association with cerebral perfusion defects as detected by 99mTc-HMPAO SPECT. AB - Anticardiolipin antibodies (ACA) belong to a heterogeneous group of antibodies directed against negatively charged phospholipids. In patients with rheumatic disorders, their presence has been correlated to the occurrence of thromboembolic complications, thrombocytopenia, abortions and other disease manifestations. Several studies have revealed the detection of mostly high-titre ACA in a significant proportion of HIV-infected patients without any known clinical relationship. In our study, ACA were detected in 17/34 HIV-infected patients, and their presence was significantly associated with the detection of cerebral perfusion abnormalities by 99mTc-HMPAO SPECT. SPECT scans were classified as normal or as focal or diffuse defects in uptake. Most patients (13/16) with cerebral perfusion defects had elevated ACA titres in contrast to 4/18 patients with normal SPECT findings (P = 0.002). Focal uptake defects were always associated with the presence of ACA. No correlation to clinical features or other laboratory parameters was evident. Our results suggest a possible implication of autoimmune mechanisms in the pathogenesis of cerebral perfusion abnormalities detected by SPECT scanning in HIV-infected patients. However, further studies are needed to evaluate the clinical significance and to develop possible therapeutic consequences. PMID- 7994902 TI - Intranasal inoculation of Mycoplasma pulmonis in mice with severe combined immunodeficiency (SCID) causes a wasting disease with grave arthritis. AB - Mycoplasma pulmonis or Myc. pneumoniae were inoculated intranasally to C.B-17 scid/scid mice (severe combined immunodeficient (SCID) mice). Immunocompetent C.B 17 mice were inoculated as controls. During the observation period of 5 weeks the mice were killed and necropsied. Mycoplasma pulmonis was recovered from all of the inoculated mice, and dissemination to various tissues increased with time. SCID mice, unlike immunocompetent mice, did not show lung lesions but exhibited severe inflammatory changes of the joints. Mycoplasma pulmonis, however, was isolated both from the lungs and the articular lesions. In addition, SCID mice infected for more than 3 weeks suffered from a pronounced loss of weight and emaciation. In the experiment with Myc. pneumoniae the agent could be reisolated, but lesions were not found in any of the infected mice. Mycoplasma pulmonis infection in SCID mice may be useful as a model of arthritis in immunodeficient humans. PMID- 7994901 TI - Cytomegalovirus hepatitis: characterization of the inflammatory infiltrate in resistant and susceptible mice. AB - Mice susceptible and resistant to murine cytomegalovirus (MCMV) were infected with this virus and livers were harvested after 2-231 days. Cryostat sections were stained to visualize cells bearing CD4, CD8 or Mac-1 antigens. Mac-1+ cells were prevalent in inflammatory foci after 2 days. These cells persisted in susceptible BALB/c and A/J mice, but disappeared from livers of resistant C57Bl/6 and CBA/CaH mice by day 28. T cell inflammation peaked on days 7-11. This declined by day 56 in C57Bl/6 and CBA/CaH mice, but persisted in BALB/c and A/J mice for at least 231 days. Persistent CD8+ cells were dispersed throughout the parenchyma. More CD8+ cells were observed 7-14 days after infection in the livers of bg/bg (natural killer (NK) cell-deficient) C57Bl/6 and CBA mice, and in C57Bl/6 mice depleted of NK1.1 cells by MoAb. Thus, mice of strains susceptible to MCMV exhibit hepatitis characterized by persistence of dispersed CD8+ cells. This phenomenon may be limited by NK cells in resistant strains. PMID- 7994904 TI - Evaluation of Onchocerca volvulus-specific IgG4 subclass serology as an index of onchocerciasis transmission potential of three Gabonese villages. AB - The major objective of this study was to evaluate the usefulness of IgG4 ELISA and Western blot analysis, using a crude extract of Onchocerca volvulus adult worms as antigens, for diagnosing onchocerciasis in a Gabonese paediatric population with mixed filarial infections. The subjects had loaisis, streptocercosis or mansonellosis in addition to onchocerciasis. Control sera from loaisis or mansonellosis subjects residing outside the endemic zone were used to provide the cut-off point for positive results. The IgG4 ELISA had a specificity of 96% but a lower sensitivity of 78.7%. It detected 25 onchocerciasis cases out of 65 individuals who were negative on parasitological examination. Furthermore, the ELISA provided a more accurate picture of onchocerciasis transmission in a village with very low skin microfilarial load. A 27.5-kD antigen was identified on Western blots as a marker of onchocerciasis. The paediatric population provided a reliable window for assessing the parasitologic and serologic parameters in the three villages with disparate levels of onchocerciasis transmission. PMID- 7994903 TI - Cross-regulatory role of interferon-gamma (IFN-gamma), IL-4 and IL-10 in schistosome egg granuloma formation: in vivo regulation of Th activity and inflammation. AB - This study examined the relationship of IL-4, IL-10 and IFN-gamma with regard to the local granuloma (GR) and draining lymph node (LN) response to Schistosoma mansoni eggs. Synchronized GR were induced in naive and schistosome-infected mice at the vigorous (8 weeks) and late chronic (20 weeks) stages. In LN cultures, IL 10 and IFN production peaked on day 4 and was greatest for 8 week-infected mice. All GR cultures contained IFN, but compared with naive mice IL-10 production was accelerated at 8 weeks and abrogated at 20 weeks, consistent with expansion and abatement of Th2 activity. Cytokine neutralization was performed in egg challenged, naive mice that were adoptively sensitized with lymphoid cells from 8 week-infected donors. GR size, GR macrophage tumour necrosis factor (TNF) production and egg antigen-elicited IL-2, IL-4, IL-5, IL-10 and IFN were examined on day 4 of GR formation. Anti-IFN augmented GR area by 40%, increased local IL-4 and IL-10, but decreased IFN and TNF production. In corresponding LN cultures, IFN decreased by about 50%, while IL-2, IL-4, IL-10 and IL-5 increased by nearly two-, four-, five- and six-fold, respectively. Anti-IL-10 did not affect GR size or GR cytokines, but abrogated GR area by 40%, along with a reduction in local IL 4 and TNF production. In LN, IL-4 depletion reduced IL-4 and IL-5 by 60-70% and increased IFN levels. These results support the notion of a cross-regulatory network in which IFN inhibits Th2 and IL-10 inhibits Th1 cells. IL-4 fosters Th2 cells differentiation in LN, but also performs a critical recruitment function in the eosinophil-rich schistosome egg-induced GR, whereas IFN contributes to enhanced GR macrophage function. PMID- 7994905 TI - Identification of a 46-kD latex protein allergen in health care workers. AB - Latex allergy is an occupational hazard for health care workers. Extractable latex proteins are known to be allergenic, but most latex allergens have not been specifically identified. The purpose of this study was to characterize the IgE response of latex-allergic patients to latex proteins and to identify common protein allergens. Serum was obtained from 40 individuals who were skin test positive to latex; 85% were health care workers. Western blots for IgE reactivity were performed using both ammoniated (AL) and non-ammoniated (NAL) latex proteins and IgE-reactive NAL proteins were analysed by microsequence analysis. The patients were grouped according to common patterns of reactivity. Pattern 1, the most common pattern of reactivity (9/40 patients) recognized two protein bands in both NAL and AL at 46 and 110 kD. A second, heterogeneous pattern of reactivity (pattern 2) recognized a diffuse pattern of polypeptides in the AL preparation. The n-terminal amino acid sequences for allergens at 14, 18, 29, 46 and 110 kD were determined. Sequence analysis identified the 14-kD and 18-kD allergens as the hevein proprotein. The 46-kD and 110-kD had identical sequences which were unique from known latex proteins. We conclude that multiple latex proteins are allergens with hevein preprotein and a previously unidentified 46/110-kD protein being commonly recognized in health care workers. PMID- 7994906 TI - Antibodies to EYRKK vesicular stomatitis virus-related peptide account only for a minority of anti-Ro60kD antibodies. AB - Previous studies demonstrated a possible antigenic relation between the carboxyl terminal portion of anti-Ro60kD autoantigen and a nucleocapsid protein (N) of vesicular stomatitis virus (VSV). In order to investigate whether anti-Ro60kD autoantibodies react with the VSV homologous region of the Ro60kD protein we synthesized, according to Merrifield's method, the EYRKKMDI octapeptide (8p) sharing a common sequence with the N protein of VSV. Sera from 61 patients with autoimmune rheumatic diseases (34 systemic lupus erythematosus (SLE), 21 Sjorgren's syndrome (SS) and six rheumatoid arthritis (RA)) as well as 59 from normal blood donors were tested for the presence of anti-Ro60kD autoantibodies by ELISA and immunoblot (IB) and anti-8p antibodies by ELISA. Antibodies to 8p were found in 9/31 of anti-Ro60kD IB-positive sera, 5/30 of anti-Ro60kD-negative sera and 2/59 of normal control sera. The concordance between the anti-8p ELISA and the anti-Ro60kD IB was very poor (chi 2 = 0.71, P = 0.4) in contrast to the anti Ro60kD ELISA and the anti-Ro IB (chi 2 = 27.6, P = 10(-7)). Subsequent affinity purification of the anti-8p antibodies from a strong positive anti-8p and anti Ro60kD SLE serum yielded 95% depletion of the anti-8p activity and 37% reduction of the anti-Ro60kD activity. Inhibition assays with the affinity-purified anti-8p antibodies demonstrated that the octapeptide gave 94.5% inhibition of the anti Ro60kD activity, while Ro60kD protein led to 42.3% inhibition of the anti-8p. Preincubation of the serum with the octapeptide produced 4% inhibition of anti Ro60kD ELISA. These results indicate that the anti-8p antibodies account only for a minority of the anti-Ro60kD autoantibodies. PMID- 7994907 TI - Enhanced synthesis of cytokines by peripheral blood monocytes cultured in the presence of autoantibodies against U1-ribonucleoprotein and/or negatively charged molecules: implication in the pathogenesis of pulmonary hypertension in mixed connective tissue disease (MCTD). AB - An attempt was made to determine whether addition of purified autoantibodies against U1-ribonucleoprotein (RNP) and negatively charged molecules (cardiolipin and double-stranded (ds) DNA) to cultures of peripheral blood monocytes could enhance the synthesis of cytokines in patients with MCTD and normal healthy volunteers. It was found that: (i) at the baseline, levels of cytokines such as IL-1 alpha, IL-1 beta and IL-6 extracellularly released by or associated with monocytes were significantly higher in MCTD patients than in normal subjects; (ii) addition of antibodies against U1-RNP to cultures of MCTD monocytes resulted in a significant overall increase of the released and cell-associated IL-1 alpha, IL-1 beta and IL-6. On the other hand, addition of antibodies against cardiolipin or dsDNA to cultures of MCTD monocytes resulted in a significant increase of released and/or cell-associated IL-1 alpha and IL-1 beta; (iii) addition of these autoantibodies to cultures of normal monocytes resulted in a significant overall increase of released and cell-associated IL-1 alpha, IL-1 beta and IL-6. The extent of enhancement of cytokines released by or associated with monocytes was greater in normal subjects than in MCTD patients; (iv) a F(ab')2 preparation of autoantibodies against U1-RNP also enhanced the level of released and cell associated IL-1 alpha. Our findings that both autoantibodies against U1-RNP and negatively charged molecules were able to enhance the synthesis of cytokines by monocytes suggest that these autoantibodies might cause derangement of endothelial cells and lead to proliferative vasculopathy, which is a characteristic of pulmonary hypertension in MCTD. PMID- 7994908 TI - Suppression of experimental systemic lupus erythematosus (SLE) with specific anti idiotypic antibody-saporin conjugate. AB - The importance of the idiotypic network is represented in experimental SLE induced by active immunization of naive mice with an anti-DNA idiotype (Ab1) emulsified in adjuvant. The mice after 4 months of incubation generate Ab3 having anti-DNA activity. In addition, the mice develop other serological markers for SLE associated with clinical and histopathological manifestations characteristic of the disease. To confirm further the etiological role of the idiotype in this experimental model, the mice were treated with specific anti-idiotypic antibodies (anti-Id) which were also conjugated to a toxin-saporin (Immunotoxin (IT)). Pretreatment of hybridoma cell line producing the anti-anti-Id (anti-DNA = (Ab3)) for 48 h with the anti-Id MoAb (Ab2) reduced the production of anti-DNA by 58%, while pretreatment with the IT resulted in 86% decrease in anti-DNA secretion (saporin alone had only 12% effect). The anti-Id MoAb had no effect on the production of immunoglobulin by an unrelated cell line. In vivo treatment of mice with experimental SLE led to a significant decrease in titres of serum autoantibodies, with diminished clinical manifestations. The results were more remarkable when the IT was employed. These suppressive effects were specific, since an anti-Id treatment of experimental anti-phospholipid syndrome was of no avail. The anti-Id effect was mediated via a reduction in specific anti-DNA antibody-forming cells, and lasted only while anti-Id injections were given. Discontinuation of the anti-Id injection was followed by a rise in titres of anti DNA antibodies. No immunological escape of new anti-DNA Ids was noted. Our results point to the importance of pathogenic idiotypes in SLE and to the specific potential of implementing anti-idiotypic therapy, enhanced by the conjugation of the anti-Id to an immunotoxin, in particular one with low spontaneous toxicity. PMID- 7994909 TI - T cell reactivity to proteinase 3 and myeloperoxidase in patients with Wegener's granulomatosis (WG). AB - T cell-mediated immunity is hypothesized to play an important role in the pathogenesis of granulomatous inflammation and vasculitis as found in patients with WG. The antigenic specificities of those T cells remain, however, unknown. Anti-neutrophil cytoplasmic antibodies (ANCA) present in patients with WG are directed to proteinase 3 (PR3) and myeloperoxidase (MPO). In the present study we investigated the proliferative capacity of peripheral blood mononuclear cells (PBMC) from patients with WG and age- and sex-matched controls in response to the WG autoantigens PR3 and MPO. Possible mitogenic effects of active PR3 and toxic effects of active MPO were excluded by using heat-inactivated PR3 and MPO. Antigen-specific stimulation induced by these autoantigens was studied by using processed PR3 and MPO in the lymphocyte stimulation test (LST). Proliferation induced by processed antigen correlated with that by heat-inactivated free antigen. The general capacity to proliferate in response to mitogens and recall antigens did not differ between patients and controls. However, patients with WG who were or had been positive for PR3-ANCA (n = 17) responded more strongly to PR3 than to MPO and showed higher responses to PR3 compared with controls (n = 13). Within the PR3-ANCA group T cell proliferation did not correlate with ANCA titre. In a small group of patients with MPO-ANCA (n = 5) no differences were observed compared with controls for MPO-specific proliferation. The data presented demonstrate that autoreactive PR3-specific T cells are present in patients with WG. Their fine specificity and possible role in the pathogenesis of WG have to be defined in further studies. PMID- 7994910 TI - IgG subclass distribution of thyroglobulin antibodies in patients with thyroid disease. AB - The IgG subclass distribution of thyroglobulin antibodies (TgAb) has been studied in Hashimoto and Graves' patients by several investigators with conflicting results, in part explainable by methodological problems. We have recently developed a quantitative ELISA to measure in absolute terms the serum concentration of TgAb subclasses. The aim of the present study was to apply this method in a large series of patients with autoimmune as well as, for the first time, non-autoimmune thyroid diseases. We examined 28 patients with Hashimoto's thyroiditis, 30 with Graves' disease, 21 with thyroid carcinoma and 18 with non toxic goitre, all selected for the presence of TgAbs. The results indicated that TgAbs in thyroid diseases were not restricted to any particular isotype, but comprised all four IgG subclasses. IgG1 was represented similarly in the four groups. The same was true for IgG3, even though its contribution to the total antibody content was very small. IgG4 was the dominant subclass in patients with Graves' disease, thyroid carcinoma and non-toxic goitre, probably reflecting a prolonged antigenic challenge. In Hashimoto's thyroiditis IgG2 was dominant, possibly because T helper lymphocytes infiltrating the thyroid are typically Th1 type. PMID- 7994912 TI - Circulating monocytes are activated in newly diagnosed type 1 diabetes mellitus patients. AB - Investigations in the BB rat and the non-obese diabetic (NOD) mouse have provided substantial evidence for the involvement of the monocyte/macrophage system in the development of type 1 diabetes mellitus. However, it is not known whether monocytes play the same role in the pathogenesis of human type 1 diabetes. We investigated this problem in a longitudinal study of 29 recent-onset type 1 diabetes mellitus patients. Monocyte chemotaxis, phagocytosis and superoxide production as well as metabolic and haematological parameters were studied immediately after diagnosis and 6 months later. At diagnosis the patients had activated casein and C5a chemotaxis (casein 70 +/- 9 versus 150 +/- 5 (mean +/- s.e.m.), P < 0.001; C5a 137 +/- 10 versus 158 +/- 5, P < 0.05 (activation immobilizes monocytes, reducing the measured values)), and activated superoxide production (3.6 +/- 0.3 versus 3.0 +/- 0.3, P < 0.05). After 6 months casein chemotaxis (115 +/- 16 versus 150 +/- 5, P < 0.05) and Candida phagocytosis (3.3 +/- 0.1 versus 2.8 +/- 0.2, P < 0.001) were still activated. There was no correlation with other clinical or paraclinical parameters. We conclude that the circulating monocytes in newly diagnosed type 1 diabetes patients are activated. It is reasonable to expect that monocytes at the local site of inflammation in pancreas are even further activated. This could play a pathogenic role in beta cell destruction. PMID- 7994911 TI - Perforin expression by thyroid-infiltrating T cells in autoimmune thyroid disease. AB - Infiltration of the thyroid gland by lymphocytes is a hall-mark of autoimmune thyroid disease; it is particularly evident in Hashimoto's thyroiditis but is also seen in most patients with Graves' disease. Infiltrating cells are comprised primarily of T lymphocytes, of which only a minority appears to be activated. Their precise pathogenic role is largely unknown. Since perforin has been a marker for functionally activated cytotoxic T cells in situ we elected to assess the presence of perforin-containing cells in thyroid-infiltrating lymphocytes and establish their phenotype. Cells were isolated from seven subtotal thyroidectomy specimens, five from patients with Graves' disease and two with Hashimoto's thyroiditis. The novel findings were as follows: CD4+ perforin-containing T cells occurred only in Hashimoto's glands, suggesting a class II-restricted component of cytotoxicity; in Graves' disease, and to a lesser extent in Hashimoto's, perforin-expressing cells were primarily T cell receptor alpha beta- CD4-CD8- (double negative); double negative perforin-containing cells in peripheral blood of normal individuals were largely gamma delta + T cells. In Hashimoto's samples, the predominant population of T cells expressing perforin was CD8+. By comparison, in studies of the synovial fluid of knee joints from patients with rheumatoid arthritis only a minor population of the perforin-containing cells was double-negative. The data suggest significant differences in cytotoxic autoimmune mechanisms between the two autoimmune thyroid diseases. Functional characterization of double-negative T cells is necessary to define their role in autoimmunity. PMID- 7994913 TI - T cell receptor V-gene usage in oral lichen planus; increased frequency of T cell receptors expressing V alpha 2 and V beta 3. AB - In order to analyse the clonality of T cells in the inflammatory infiltrate of oral lichen planus (OLP), mucosal biopsies were obtained from seven patients with manifest disease. The biopsies were stained with MoAbs directed against 11 different T cell receptor (TCR) V-gene families, anti-CD4, anti-CD8 and IL-2 receptor (IL-2R). For comparison, the frequencies of the different TCR V-families were determined in biopsies from five patients with oral candidosis as well as in peripheral blood from three patients with OLP and from six healthy blood donors (HBD). The occurrence of the investigated TCR V-families varied between 0% and 7% in venous blood obtained from both HBD and OLP patients. T lymphocytes expressing the TCR V beta 3 and V alpha 2 in OLP biopsies were, however, detected in frequencies ranging between 18% and 40% of the total fraction of lymphocytes, a consistent finding for all the OLP infiltrates studied. The other nine TCR V families examined appeared in low frequencies both in biopsies and in peripheral blood. V alpha 2+ and V beta 3+ cells were often localized adjacent to the basal membrane. In contrast, T cells in Candida-induced lesions did not express a biased TCR distribution, and most V-families studied appeared in frequencies of 0 6%. Thus, T lymphocytes in OLP lesions express a substantially higher frequency of TCR V alpha 2 and V beta 3 than expected from the distribution in blood. The clonal expansion of T cells observed in OLP suggests that a superantigen is involved in the pathogenesis of the disease. Whether this superantigen is of exogenous or endogenous origin needs to be investigated. PMID- 7994914 TI - Early detection of the allogeneic effect in the mixed lymphocyte reaction (MLR) by anti-CD3 IgA mouse monoclonal antibody. AB - MLR is a 6-day routine proliferation assay used to demonstrate HLA disparity between two individuals. However, on day 2 only a negligible proliferation can be detected. In contrast, we found a significant increase of the extent of proliferation if an anti-CD3 IgA antibody was present in the culture. Since the CD3 proliferation pathway cannot be triggered by an antibody of IgA isotype the result was interpreted as a consequence of a synergism between the allogeneic stimulus and the anti-CD3 antibody effect. The level of this proliferation well correlates with the HLA difference, thus suggesting the use of this methodology for a rapid detection of the allogeneic reaction. PMID- 7994915 TI - MHC-associated immunopotentiation affects the embryo response to teratogens. AB - The present study was performed to evaluate whether the effect of environmental teratogens can be modified by maternal immunostimulation. Two chemicals, cyclophosphamide (CP) and 2,3-quinoxalinedimetanol,1,4-dioxide (QD) were used as the reference teratogens (RT). The response to these RT was investigated in two animal models: (i) primigravid C57Bl/6 mice who underwent intrauterine immunization with allogeneic paternal (CBA/J), third-party (BALB/c) or syngeneic male splenocytes 21 days before mating; (ii) C57Bl/6 and CBA/J mice who were treated with RT during the second pregnancy only, after a different mating combination (syngeneic or allogeneic) in the first and the second pregnancy. Different doses of CP and QD were injected on days 12 and 9 of pregnancy, respectively. On day 19 of pregnancy implantation sites, resorptions, live and dead fetuses were recorded and live fetuses were examined for external and internal malformations with methods routinely used in teratological study. It was shown that intrauterine immunopotentiation with allogeneic paternal splenocytes clearly enhances the tolerance of F1 embryos to RT. Thus, in CP-treated females the resorption rate and the proportion of malformed fetuses were significantly reduced. It was followed by an almost two-fold increase in fetal weight. The protective effect of such immunization in QD-treated females was manifested as a dramatic decrease of the proportion of malformed fetuses and the resorption rate. Syngeneic splenocytes could not significantly influence an embryo's sensitivity to RT. The response to RT was also significantly weaker in the second pregnancy of female mice mated twice allogeneically than that observed in allogeneically mated primigravid mice. These results show that the embryo's response to environmental teratogens may be influenced by fetomaternal immune interactions. PMID- 7994917 TI - Introduction to review series on animal models of human disease. PMID- 7994916 TI - Characterization of naturally occurring autoantibodies against tumour necrosis factor-alpha (TNF-alpha): in vitro function and precise epitope mapping by phage epitope library. AB - Naturally occurring autoantibodies against cytokines exist in the sera of patients with autoimmune diseases as well as in the sera of normal individuals. We report here that affinity-purified autoantibodies against human TNF-alpha from one rheumatoid arthritis (RA) patient inhibited the cytotoxic effect of TNF-alpha on the mouse fibrosarcoma cell line WEHI 164, by 50%. In an attempt to predict the autoantibodies' recognition site on TNF-alpha protein we screened a random nanopeptide phage library with the affinity-purified TNF-alpha autoantibodies. Among 63 random selected clones, 46 clones carried the sequence ASSLLASSP, NSSPYLNTK or PQSPGSSFP. Frequency analysis of the relative occurrence of the 20 amino acids in the nanopeptides displayed by 50 random bacteriophages picked before selection and 63 after selection to bind to TNF-alpha autoantibodies indicated that proline (P < 0.0003) and serine (P < 0.04) are involved in the binding of the autoantibodies to the phages. Furthermore, we demonstrated that three synthetic peptides (ASSLLASSP, NSSPYLNTK and PPLKPVIDE) displayed by the selected phages reduced the binding of the autoantibodies to TNF-alpha protein by 50%. Interestingly, the sera of mice (BALB/c) immunized with phages displaying ASSLLASSP and NSSPYLNTK peptide showed an anti-TNF-alpha response as detected by ELISA. This response was not found in mice immunized with the wild type phage. Thus, the recombinant phages selected from the phage libraries could be used as carrier for immunization, and therefore as a tool for vaccine development. This work sets the stage for experiments designed to isolate ligands for protective antibodies. PMID- 7994918 TI - Infection and autoimmunity: a story of the host, the pathogen, and the copathogen. PMID- 7994919 TI - Neutrophil chemotaxis induced by immune complexes. AB - In the current work we have analyzed the ability of different soluble immune complexes (IC) prepared with IgG antibodies to induce neutrophil chemotactic responses in vitro. While, in all cases, IC were able to induce neutrophil migration in a concentration-dependent fashion, IgG antibodies alone were completely unable to induce locomotor responses. Checkerboard analysis indicated the chemotactic nature of motility. On the other hand, chemotaxis induced by IC was markedly inhibited by IV. 3, a monoclonal antibody (mAb) to Fc gamma RII, slightly reduced by 3G8 F(ab')2, a mAb to Fc gamma RIII, and nearly abrogated by both mAbs. The impact of IC on neutrophil migration induced by FMLP was also studied. We found that when a suboptimal concentration of FMLP was employed, the simultaneous addition of IC increased the migration acting in additive form. The significance of these results is discussed. PMID- 7994921 TI - Elevated serum levels of IL-10 and IFN-gamma in patients with acute Plasmodium falciparum malaria. AB - Serum levels of interleukin-10 (IL-10) and interferon-gamma (IFN-gamma) were determined in 37 patients with acute Plasmodium falciparum malaria in Bangkok, Thailand. Serum levels of IL-10 and IFN-gamma were markedly elevated in patients with malaria prior to treatment (717 +/- 260 pg/ml versus 2.2 +/- 1.3 pg/ml in healthy controls; 123 +/- 71 pg/ml versus 29 +/- 9 pg/ml, respectively; mean +/- SD). Serum levels of IFN-gamma and IL-10 dropped significantly during treatment and were normal 14 and 21 days, respectively, after treatment was started. Prior to therapy a correlation between serum levels of IFN-gamma and IL-10 existed (r = 0.563). These results suggest that stimulatory and inhibitory cytokines for macrophage activation and/or antibody production (i.e., TH1- and TH2-type immunoreaction, respectively) are coexpressed during acute P. falciparum infection and stress the multifactorial network between host and parasite in malaria immunology. PMID- 7994920 TI - The ability of CD4+ cells from HIV+ individuals to express CD40 ligand after in vitro stimulation is not impaired. AB - Interaction between the B cell glycoprotein CD40 and its ligand (CD40L), expressed by activated T cells, is of crucial importance in the generation of specific antibody response, which is impaired in HIV+ individuals. We studied the expression of CD40L by lymphocytes activated with PMA plus ionomycin in 17 HIV+ individuals and 12 healthy donors. In HIV+ individuals, the percentage of cells expressing CD40L was lower than that in the controls (22.6 +/- 14.7 vs 40.1 +/- 12.0; P < 0.002) and clearly correlated with that of CD4+ peripheral blood lymphocytes (r = 0.83; P < 0.001); therefore, the reduced CD40L expression might be explained by the decrease of the CD4+ cells. In fact, the expression of CD40L by purified CD4+ cells was comparable in individuals with and without HIV infection. These data indicate that the ability of CD4+ cells from HIV individuals to express CD40L is not impaired, at least after optimal stimulation in vitro. PMID- 7994922 TI - Human autoimmune diabetes mellitus: lessons from BB rats and NOD mice--Caveat emptor. PMID- 7994923 TI - Cellular signals for the induction of human interleukin-1 receptor antagonist. AB - The polypeptide cytokine interleukin-1 (IL-1) mediates a broad spectrum of inflammatory, metabolic, physiologic, hematopoietic, and immunologic properties. An inhibitor of IL-1 (IL-1ra) has been purified from monocytes, and its DNA has been cloned. Human immunoglobulin G stimulates monocytes to make IL-1ra, but the monocyte receptor(s) for this induction remains a mystery. Therefore, the cellular Fc receptors (Fc gamma R) for IgG that induce IL-1ra production were tested. The Fc gamma R were defined and quantitated by flow cytometer. Anti-Fc gamma RIII (CD16), anti-Fc gamma RII (CD32), and anti-Fc gamma RI (CD64) had no blocking effect on IL-1ra production from monocytes after IgG stimulation. Monocytes express Fc gamma RI and II and respond as anti-CD32 to secrete IL-1ra; neutrophils express Fc gamma RII and III and respond as anti-CD16 to secrete IL 1ra; macrophages express Fc gamma RI, II, and III and respond as both anti-CD16 and anti-CD32 to secrete IL-1ra. These studies strongly suggested that both Fc gamma receptor II and III play a key role in IL-1ra production. PMID- 7994924 TI - Serum-soluble receptors for tumor necrosis factor-alpha and interleukin-2, and neopterin in acute rheumatic fever. AB - Immune activation may play an important role in the pathogenesis of acute rheumatic fever (ARF). The objective of the present study was to investigate serum concentrations of various markers of immune activation in ARF patients. Sera of 32 patients with ARF were investigated, 20 of them in follow-up. Radioimmunoassay was used to quantify neopterin and ELISA for the measurement of 55-kDa-type soluble tumor necrosis factor receptor (sTNF-R) and soluble interleukin-2 receptor (sIL2-R). Markers of immune activation were found to be raised in 48% (sTNF-R), 28% (sIL2-R), and 78% (neopterin) of patients at the onset of ARF. There were significant correlations between the concentrations of neopterin and sTNF-R (rs = 0.60, P < 0.001) or sIL2-R (rs = 0.35, P < 0.05). Higher neopterin concentrations were found in patients with combined aortic and mitral insufficiency than in patients with mitral valve lesions alone (U = 2.67, P < 0.05) or without valve lesion (U = 2.36, P < 0.05). Increased concentrations of neopterin, sTNF-R, and sIL2-R demonstrate activation of the cellular immune system in patients with ARF. Higher serum neopterin concentrations are associated with development of combined aortic and mitral insufficiency during the first episode of ARF. PMID- 7994925 TI - Human immune response to DNP-modified autologous cells after treatment with a DNP conjugated melanoma vaccine. AB - Immunizing patients with metastatic melanoma by injection of autologous tumor cells modified by DNP induces inflammatory responses in metastatic masses, which is sometimes associated with tumor regression. To elucidate this phenomenon, we studied the immune response to DNP-modified cells in these patients. All developed DTH to DNP-modified autologous lymphocytes (mean +/- SE: 13.3 +/- 1.3 mm), but not to TNP-modified lymphocytes. Larger responses (21.9 +/- 3.6 mm) were elicited by DNP-modified autologous melanoma cells. In 8/11 patients tested, PBL proliferated in vitro when stimulated by autologous DNP-modified lymphocytes, and in 5 patients the stimulation resulted in production of interferon-gamma. DNP modified autologous melanoma cells elicited lymphocyte responses as well. PBL from 1 patient were expanded by culture in IL2 and repeated restimulation with DNP-modified B lymphoblastoid cells. This T cell line proliferated and produced interferon-gamma but not IL4, when stimulated by autologous DNP-modified lymphocytes or melanoma cells. Both CD4+ and CD8+ subpopulations responded as determined by panning experiments and by testing of phenotypically homogeneous cultures obtained by limiting dilution. Studies of a stable CD8+ subline of the expanded T cells indicated that the response to DNP-modified cells was MHC restricted, since it was blocked by antibody to class I determinants. Moreover, these T cells were able to respond to allogeneic DNP-modified stimulators that were matched at one or both HLA-A loci, but not to stimulators that were HLA-A mismatched. Finally, the CD8+ subline killed DNP-modified autologous melanoma cells, but not an HLA-A mismatched allogeneic melanoma, in a 6-hr 51Cr-release assay. These results may have significant implications for understanding the pathogenesis of drug-induced autoimmunity and for the development of new approaches to cancer immunotherapy. PMID- 7994926 TI - Upper eyelid retraction in the absence of other evidence for progressive ophthalmopathy is associated with eye muscle autoantibodies. AB - We have studied 25 clinically euthyroid patients with eyelid lag and retraction referred to thyroid/eye clinic for clinical and orbital imaging evidence of extraocular eye muscle (EM) involvement, evidence of progressive ophthalmopathy and serum antibodies reactive with EM membrane antigens in immunoblotting. Fourteen patients had Graves' hyperthyroidism, 5 had Hashimoto's thyroiditis, and 6 had euthyroid Graves' disease. By carrying out orbital imaging we showed EM abnormalities in 10 of 23 patients (43%). Serum antibodies reactive with EM membrane antigens were detected in 96% of patients. Antibodies reactive with a 64 kDa antigen were detected in 66% of patients, while those reactive with 35-, 55-, and 95-kDa antigens were found in 21, 33, and 25% of patients, respectively. Antibody prevalences compared to normals were significantly different (P < 0.005) only for the 64-kDa protein. The prevalence and the degree of reactivity of 64 kDa antibodies were significantly different in patients with abnormal EM compared to those with normal EM at orbital imaging (P < 0.04 and P < 0.01, respectively). The results of this work suggest that in some patients inflammation of the eyelid muscles may be an isolated feature of ophthalmopathy and remains as the only sign of a "subclinical" eye disease in patients with thyroid autoimmunity. PMID- 7994927 TI - C3-independent glomerulonephritis in guinea pigs: dependence upon primary humoral response. AB - We used C3-deficient (C3D) guinea pigs to evaluate the role of C3 in an active model of experimental nephritis. Normal strain 2 (C3N, n = 13) and C3D (n = 6) guinea pigs were immunized with cationized bovine gamma-globulin (CBGG). Fourteen days later (Day 0), daily intravenous injections of CBGG were given for 3 to 7 days and the animals were sacrificed on Day 10 or 21. Immunofluorescence (IF) microscopy of renal tissue revealed two patterns of glomerular IgG deposition: granular loop (11/13 C3N, 3/6 C3D), and predominantly mesangial (2/13 C3N, 3/6 C3D). Codeposited C3 was seen in all C3N and in no C3D animals. Electron microscopy showed subepithelial deposits in all. A significant correlation (P < 0.005) was seen between an animal's IF pattern and its level of serum antibodies to CBGG; those with lower antibody levels exhibited the mesangial pattern. C3D animals had lower mean antibody levels than C3N (P < 0.01), but both IF patterns were represented. Urine protein concentration, which was increased relative to controls, did not differ between C3N and C3D groups, but was significantly greater in those with loop IF. Serum albumin was significantly reduced in animals with loop IF. C3N animals showed a significant reduction in mean serum C3. In this model, immune deposit location and degree of proteinuria are independent of C3 deposition and dependent upon the level of antibody response to CBGG. Induction of antibody to CBGG is impaired in the absence of C3. PMID- 7994928 TI - Localization and morphology of antigen-presenting cells in the adenoid of children with otitis media with effusion. AB - This study describes the localization of antigen-presenting cells (APC) in the different compartments in adenoids of children with otitis media with effusion (OME) and "healthy" children and adults. It is shown that the adenoid of children with OME contains a relatively high number of OKT6 and RFD1 positive cells. Moreover, accumulations of these cells are present in the extrafollicular areas of these adenoids. Very occasionally dendritic cells in the epithelial microenvironment contain Birbeck granules, indicating characteristic Langerhans cells. These OKT6 positive cells are not seen in the adenoids of the control group. Our results clearly show a relation between the presence of dendritic cells and the occurrence of OME. No differences are seen in localization and morphology of the APC in the studied adenoids. PMID- 7994929 TI - Macrophage inflammatory protein-1 alpha expression in vivo and in vitro: the role of lipoteichoic acid. AB - Lipoteichoic acid (LTA), a component of the cell wall of most gram-positive bacteria, has been shown to play a significant role in the initiation and progression of bacterial infection. However, little is known of its position in the cytokine network involved in the induction and perpetuation of inflammation. In this study, we assessed whether the macrophage activating and chemotactic cytokine macrophage inflammatory protein-1 alpha (MIP-1 alpha) was expressed in the setting of localized gram-positive infection. Furthermore, we determined whether LTA purified from either Staphylococcus aureus or Streptococcus pyogenes could induce the expression of MIP-1 alpha mRNA and protein from human blood monocytes. Immunohistochemical staining of human endocardial samples obtained from patients with acute S. aureus endocarditis revealed cell-associated MIP-1 alpha expression by neutrophils, macrophages, and fibroblasts. Treatment of human peripheral blood monocytes in vitro with LTA isolated from either S. aureus or S. pyogenes resulted in both the time- and dose-dependent expression of MIP-1 alpha mRNA. Similarly, staphylococcal and streptococcal LTA induced the dose-dependent production of MIP-1 alpha protein after 24 h in culture. These studies suggest that LTA may play an important role in triggering the recruitment and activation of leukocytes that characterizes the host response to gram-positive bacterial invasion. PMID- 7994930 TI - Human monocytes produce monocyte chemoattractant protein 1 (MCP-1) in response to a synthetic peptide derived from C-reactive protein. AB - We reported previously that a synthetic peptide (RS-83277) derived from human C reactive protein (CRP) augmented human monocyte/macrophage tumoricidal activity and cytokine production. RS-83287, a synthetic peptide derived from a different CRP site, was ineffective. Because chemoattractant properties have been attributed to some CRP-derived peptides, we hypothesized that RS-83277, in addition to activating effects, might promote human monocyte chemotaxis. Results indicated that neither CRP peptide RS-83277 nor RS-83287 was, itself, a chemoattractant. RS-83277, but not RS-83287, however, elicited time-dependent production of monocyte chemoattractant activity in conditioned media (CM) of cultured human mononuclear leukocytes and purified, adherent monocytes (MO). CM from nonadherent MO contained no activity, indicating that adherence was required for monocyte response. Monocyte chemoattractant activity was dose-dependent and was removed by treatment with immobilized antibody to human monocyte chemoattractant protein 1 (MCP-1) but not by irrelevant IgG. These results indicate that a specific peptide segment of CRP acts upon human adherent monocytes to promote production of the autocrine chemotactic and activating factor MCP-1. Data suggest that degraded CRP represents a complex source of biologically active peptides which, among other effects, may amplify monocyte recruitment to sites of injury. PMID- 7994931 TI - Comparison between pre- and posttreatment renal biopsies in children receiving ciclosporine for idiopathic nephrosis. AB - Fourty-two children with idiopathic nephrosis that had not been well controlled by other forms of therapy were treated with ciclosporine. Thirty-three of them were steroid dependent, 2 were partial steroid responders and 7 were steroid resistant. On pretreatment renal biopsy, performed in all patients less than 6 months before starting ciclosporine, minimal change disease (MCD) was diagnosed in 37 children and focal glomerular sclerosis (FGS) in 5. In order to evaluate the morphological changes of the renal parenchyma possibly induced by the drug, posttreatment biopsies were performed in these 42 patients: one in all patients after 4 to 28 months of ciclosporine, 2 in 23 patients after 18 to 42 months of treatment, 3 in 8 patients after 30 to 63 months of treatment and 4 in 2 patients who had been treated respectively for 62 and 63 months. The morphological changes on pre- and posttreatment biopsies were scored according to the severity of tubulointerstitial lesions. Grade I was considered when there were no significant changes of the renal parenchyma or when occasional scattered tubules with thickened basement membranes were present. Grade II was diagnosed when the biopsy showed several small foci of atrophic tubules with thickened basement membranes within stripes of interstitial fibrosis and grade III when confluent or extensive areas of interstitial fibrosis with atrophic and/or collapsed tubules were observed. On pretreatment renal biopsy, only one patient showed tubulointerstitial lesions (grade II). On the latest biopsy obtained, 18 patients showed grade I tubulointerstitial lesions, 15 grade II and 9 grade III. Unspecific arteriolopathy was observed in 10 patients.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7994932 TI - Cyclosporine treatment of lupus membranous nephropathy. AB - Few studies describe the treatment of membranous nephropathy associated with systemic lupus erythematosus. Although cyclosporine-A has been used to treat patients with the nephrotic syndrome and also with systemic lupus, only a few of these patients have had lupus membranous nephropathy. In this pilot study, we assessed the safety and efficacy of cyclosporine in ten nephrotic patients with either pure membranous lupus nephropathy (seven patients) or membranous lupus nephropathy with superimposed mild proliferative lesions (three patients). Cyclosporine (4-6 mg/kg/day) alone (2 patients), or in conjunction with low dose corticosteroids (8 patients) was given for a period of up to 43 months. Six patients achieved a nadir proteinuria of less than 1 gram daily, two patients decreased urinary protein excretion to 1-2 grams daily, and the remaining two patients continued to excrete over 2 grams of protein daily. All patients experienced symptomatic improvement of their nephrotic syndrome and serum creatinine was not significantly increased at the end of the study period. Three patients with superimposed mild proliferative lesions experienced renal and systemic lupus flares while on treatment requiring additional immunosuppressive therapy. Side-effects were minor except for transient rises in serum creatinine in one patient and a case of drug-related hepatitis possibly caused by cyclosporine. Repeat renal biopsies in five patients revealed a decrease in the lupus activity index and a rise in the chronicity index. There was an increase in the stage of the membranous nephropathy on these repeat biopsies, but a reduction in the number of fresh deposits.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7994933 TI - A light microscopic study of glomerulosclerosis in Japanese patients with noninsulin-dependent diabetes mellitus: the relationship between clinical and histological features. AB - We studied the relationships of renal lesions with clinical features and renal prognosis in 128 Japanese patients with noninsulin-dependent diabetes mellitus (NIDDM). Diabetic glomerulosclerosis (DMGS) was found in 108 cases (84.4%), and DM-associated glomerulonephritis (GN), IgA nephropathy and membranous nephropathy, was in 20 cases (15.6%). There was no significant difference in age at renal biopsy, age at DM onset, DM duration, glomerular filtration rate (GFR), urine protein and serum IgA level between patients with DMGS and DM-associated GN. With respect to histological parameters, the increase in mesangial matrix was more closely related to DM duration, GFR and urine protein than to the degree of glomerular sclerosis. The index of glomerular lesion (IGL), which was calculated by combining these two lesions, had a more significant correlation with the clinical features than the tubulo-interstitial lesions. We suggested that the mesangial change was an initiating reaction, and the interstitial one was secondary in NIDDM patients. The prognosis of renal function after renal biopsy of the patients whose serum creatinine level was less than 1.2 mg/dl, was poorer in cases with nodular lesion than in those with diffuse lesion. The grade of tubulo-interstitial lesion was also more severe in these patients with nodular lesion. However, the controls of blood glucose, blood pressure, serum total cholesterol were not different among the two groups. On the other hand, serum creatinine level of most patients with associated GN did not change for a long period, up to 10 years.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7994934 TI - Acute renal failure due to bilateral lymphomatous infiltrates. Primary extranodal non-Hodgkin's lymphoma (p-EN-NHL) of the kidneys: does it really exist? AB - Primary extranodal non-Hodgkin's lymphoma (p-EN-NHL) of the kidneys with acute renal failure as the only manifestation is very rare. The origin of neoplastic lymphoid cells in the kidneys, organs normally free of lymphoid tissue, is an unsolved problem. A literature review over the last ten years revealed only 9 adult cases, including ours that match the usual criteria: (1) renal failure as the initial presentation, (2) bilateral enlargement of the kidneys without obstruction and other organ or nodal involvement, (3) diagnosis only made by renal biopsy, (4) absence of other causes of renal failure, and (5) rapid improvement of renal function after radiotherapy or, as in our case, systemic chemotherapy. Autopsy on two patients confirmed that p-EN-NHL of the kidneys without dissemination does exist as a separate entity. PMID- 7994935 TI - Diuretics potentiate angiotensin converting enzyme inhibitor-induced acute renal failure. AB - Previous studies suggest that angiotensin converting enzyme (ACE) inhibitors cause reversible acute renal failure (ARF) in patients with hypertension, congestive heart failure (CHF), and renal disease. These patients often receive diuretics concomitantly with ACE inhibitors. The purpose of this study was to examine whether ACE inhibitors alone produce ARF or whether they do so when used in combination with diuretics. The medical records of patients taking ACE inhibitors without or with diuretics were reviewed. Complete data from 74 patients were obtained and the data were analyzed. These 74 patients had a diagnosis of hypertension, CHF or diabetes mellitus. BUN and serum creatinine values before, during, and after discontinuation of ACE inhibitor therapy for a mean period of 8.7 months were collected. Seventy-four patients were divided into two groups: Group A (n = 41) patients who received ACE inhibitors alone; Group B (n = 33) patients who received a combination of an ACE inhibitor and a diuretic. ARF developed in 1 of 41 (2.4%) Group A patients compared to 11 of 33 (33%) Group B patients. This group difference was highly significant (P < .001). In Group A, mean serum creatinine before (1.24 +/- .34 mg/dl) was identical to that 1.23 +/- .33 mg/dl) after 8.7 months of ACE inhibitor therapy, whereas in Group B, post mean serum creatinine (3.11 +/- 2.27 mg/dl) was significantly (P < .01) higher than pre-mean serum creatinine (1.65 +/- .85 mg/dl). CHF patients had a higher rate of ARF than patients with other diagnoses. Urinary electrolytes showed that 4 of 6 Group B patients had chloride concentration less than 20 mEq/l.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7994936 TI - Bone disease in calcium stone forming patients. AB - The association between idiopathic hypercalciuria and osteopenia (OP) has been recently recognized. It is not established whether or not calcium intake plays a critical role in the loss of bone mass. Fifty-five calcium stone forming patients with either absorptive hypercalciuria (AH) or fasting hypercalciuria (FH), 29 males and 26 premenopausal females, were submitted to dual photon absorptiometry at lumbar spine. Calcium intake was assessed by a 72 hr dietary record. OP was detected in 20% (11/55) of patients, being more common among men, 9/26 (35%) than in women, 2/29 (7%), p < 0.05. Male FH patients presented lower mean bone mineral density (BMD) than sex, weight and age-matched control (1.058 +/- 0.18 vs 1.209 +/- 0.13 g/cm2, X +/- SD, p < 0.05). OP was more frequent in FH patients, 7/20 (35%) than in AH patients 4/35 (11%), albeit the difference was not statistically significant. There was no correlation between calcium intake and BMD measurement. Six osteopenic male FH patients were further submitted to histomorphometric evaluation with tetracycline double labeling. Bone volume was lower than the controls (13.2 +/- 3.0 vs 27.2 +/- 3.7%, p < 0.05). Osteoid surfaces were reduced, although not significantly (10.1 +/- 8.2% vs 15.9 +/- 6.7%). Eroded surfaces were markedly increased (23.9 +/- 13.4 vs 4.2 +/- 1.4%, p < 0.05). The bone formation rate was very low with a complete lack of tetracycline double labeling in 4 patients. These data suggest low bone volume, tendency to low bone formation, increased bone resorption and a severe mineralization defect, consistent with normal or low bone turnover osteoporosis. PMID- 7994937 TI - Transesophageal echocardiographic assessment of superior vena cava thrombosis in patients with long-term central venous hemodialysis catheters. AB - In some patients with end-stage renal failure, arteriovenous fistulas cannot be created due to poor vessel conditions. Alternatively, hemodialysis (HD) can be performed using long-term central venous catheters. However, these dialysis catheters are associated with a presently unknown risk of superior vena cava (SVC) thrombosis. We examined 20 patients (11 female, 9 male, age 29-83 years) 1 48 (mean 15) months after transjugular insertion of a permanent single lumen silicone rubber HD catheter. All patients underwent both transthoracic (TTE) and biplane transesophageal (TEE) echocardiography. TTE visualized the catheter only when its tip was localized in the right atrium (2 patients), but did not succeed in adequate imaging of the SVC. In contrast, TEE allowed high quality imaging of the SVC in all patients and detected a SVC thrombosis in 6 patients; in 3 of them, caval thrombosis was subtotal. One additional patient showed a thrombus attached to the catheter tip alone. Dwelling time of catheters since insertion in the SVC was not significantly different in patients with and without thrombosis. Reduced blood flow during HD was observed in 5 of 7 patients with catheter associated thrombi but also in 4 of 13 patients without evidence for caval thrombosis by TEE. It is concluded that thrombotic occlusion of the SVC is frequent in patients with long-term central venous access; it does not necessarily correlate with clinical signs but can easily be detected by TEE. Patients with long-term central venous hemodialysis catheters should undergo transesophageal echocardiography at regular intervals. PMID- 7994938 TI - Whole blood-, plasma- and red blood cell glutathione and cysteine in patients with kidney disease and during hemodialysis. AB - There are conflicting results regarding the activity of glutathione (GSH) in patients with kidney disease. We examined whole blood-, plasma- and erythrocyte concentrations of GSH and cysteine in 12 patients with renal disease and in 14 patients on maintenance hemodialysis. Total plasma GSH concentrations were higher in patients with kidney disease than in patients maintained on hemodialysis (23.5 +/- 13.1 vs 9.1 +/- 7.5 mumol/l, p < 0.01) but erythrocyte concentrations of GSH were similar. Whole blood-, plasma and erythrocyte concentrations of GSH remained stable during hemodialysis. The total concentration of cysteine in plasma was significantly higher in patients on hemodialysis (556 +/- 258 mumol/l) as compared to patients with kidney disease (248 +/- 53 mumol/l, p < 0.001) but red blood cell concentrations were similar. Whole blood- and plasma concentrations of cysteine decreased significantly during hemodialysis. There were no significant correlations between serum creatinine and GSH or cysteine concentrations in patients on hemodialysis but when all patients were evaluated together, a significant correlation between serum creatinine and total plasma cysteine concentrations was observed (r = 0.52, p = 0.0017). PMID- 7994939 TI - Pharmacokinetic profiles of intravenous imipenem/cilastatin during slow hemodialysis in critically ill patients. AB - The pharmacokinetics of imipenem/cilastatin were determined in 7 critically ill patients undergoing slow hemodialysis (HD). All patients were anuric. Following intravenous administration of 500 mg of imipenem/cilastatin, concentrations of the drugs in the serum and dialysate were monitored during slow HD. The elimination phase half-life of imipenem was 3.1 +/- 0.3 h and that of cilastatin was 9.7 +/- 1.2 h. The total body clearance of imipenem and cilastatin was 84.0 +/- 7.2 and 32.2 +/- 2.4 ml/min, respectively. Clearance of imipenem and cilastatin during slow HD was 24.3 +/- 2.4 and 54.3 +/- 3.1%, respectively, of total body clearance. After the 10.5-h session of slow HD, serum concentrations of imipenem and cilastatin were 2.3 +/- 0.4 and 16.0 +/- 1.2 mg/l, respectively. It appears that at least 500 mg of imipenem may be needed as a supplemental dose after a session of slow HD or the application interval should be shortened to maintain a therapeutic concentration. PMID- 7994940 TI - The prevalence and significance of occult blood loss in patients with predialysis advanced chronic renal failure (CRF), or receiving dialytic therapy. AB - Hemoccult test was performed on stool specimens of 249 patients; 64 with advanced renal failure prior to dialysis (CRF), 144 on maintenance hemodialysis (HD), and 41 receiving chronic ambulatory peritoneal dialysis CAPD. Each patient collected spontaneously evacuated stool specimens on three different days. None of the patients had overt gastrointestinal bleeding prior to participation in the study. The patients were not taking aspirin, or any other ulcerogenic medication, nor receiving iron supplements at the time of study. Twelve of 64 CRF patients (18.8%), 9 of 144 HD subjects (6.3%), and 3 of 41 CAPD patients (7.3%) had Hemoccult positive stool. Twenty patients underwent diagnostic gastrointestinal (GI) evaluation and these studies demonstrated a definite GI pathology. The commonest lesion was duodenal involvement (alone or in combination with other lesions) and was found in 61.1% of the subjects. The duodenal lesions consisted of superficial erosions, duodenitis, ulcers, polyp, and arteriovenous malformation. The other common lesions were gastritis and hemorrhoids. These results underscore the need for utilization of a simple and non-invasive Hemoccult test in patients with ESRD routinely, and the positive test should be followed by a thorough gastrointestinal work up to identify the cause of occult bleeding. PMID- 7994941 TI - Serological survey of Hantavirus antibodies in chronic hemodialysis patients. PMID- 7994942 TI - Altered hemorheology in patients with IgA nephropathy. PMID- 7994943 TI - The influence of osmolality changes on blood volume-vasopressin relationship. PMID- 7994944 TI - Renal transplantation of ANCA-positive idiopathic crescentic glomerulonephritis: two-year follow-up. PMID- 7994945 TI - The clinical value of isoelectric focusing in nephrotic syndrome. PMID- 7994946 TI - Safety of 1-stage bilateral total knee arthroplasty. AB - Bilateral total knee replacements during a single operation with intramedullary femoral guide rods have been associated with the possible development of a fat embolism syndrome. To assess the safety of this procedure, in which the femoral canal was decompressed by the use of an overdrilled entrance hole and fluted guide rod, 17 unilateral and 18 bilateral consecutive total knee patients were evaluated. There were no differences between the groups on the basis of changes in chest radiographs, percentage of estimated pulmonary shunting, mental status changes, or fat and bone marrow elements drawn from a central venous catheter in the right atrium. Although no patient had free fat in the blood, bone marrow elements were found in 3 bilateral and 2 unilateral cases. No patient had clinical manifestations of a fat emboli syndrome. With appropriate femoral canal decompression, bilateral 1-stage total knee replacement appears to be a safe procedure. PMID- 7994947 TI - Quantitative and qualitative analysis of polyethylene wear particles in synovial fluid of patients with total knee arthroplasty. A preliminary report. AB - Synovial fluid from 13 knees undergoing revision total knee arthroplasty was subjected to chemical digestion and ultrafiltration. Scanning electron microscopy was used to visualize high-density polyethylene particles filtered from the fluid, and the images were analyzed using digital imaging software. This data were correlated with polyethylene wear patterns seen at the time of revision surgery. Patients' prostheses with gross polyethylene wear were differentiated from those with surface deformation and burnishing. The knees had been in situ for periods ranging from 3 to 112 months, and included 6 different prosthetic designs. The average area of the polyethylene particles measured ranged from 41 to 701 mu 2, and the total number of particles identified for each sample ranged from 38 to 279 mu 2. The largest particle identified had a surface area of 17,500 mu 2. Using the fluid volume analyzed, the particle area per milliliter of synovial fluid examined was calculated, and values ranged from 6.22 x 10(4) to 2.06 x 10(6) mu 2/ml. Visualization of high-density polyethylene using scanning electron microscopy allows greater resolution of morphologic detail than is possible with routine histologic examination using light microscopy. There were trends toward increasing particle size and total particle area in patients with gross polyethylene wear. The area of high-density polyethylene per milliliter of fluid in patients with gross wear was found to be statistically greater than that of patients without gross wear (p = 0.047). This technique offers a potentially valuable method of evaluating the status of high-density-polyethylene bearing surfaces in situ using a noninvasive technique. PMID- 7994949 TI - Cemented long-stem revision total knee arthroplasty. AB - Theoretical concerns about the use of cemented long-stemmed revision total knee arthroplasty include inducing stress shielding with adverse effects on prosthesis fixation. This study details the clinical outcome of 35 patients with 40 cemented long-stemmed kinematic stabilizer revision total knee arthroplasties at followup evaluation averaging 58.2 months (range, 24-111 months). Of these 40 revision arthroplasties, there were 25 long-stemmed tibial components and 38 long-stemmed femoral components. The Knee Society pain score improved from a preoperative value of 38 points (range, 4-80 points) to 83 points (range, 33-100 points) at last evaluation. The Knee Society function score improved from a preoperative value of 46 points (range, 5-100 points) to 64 points (range, 0-100 points) at last evaluation. Initial postoperative radiographs showed tibial bone-cement radiolucencies in 5 knees, but at final followup none of these radiolucencies had progressed. Radiolucencies developed in 5 additional tibial components by the time of final followup, but these were all incomplete and < 1 mm in width. Two femoral components had initial postoperative radiolucencies. These radiolucencies remained stable in 1 knee, whereas the other knee had asymptomatic radiographic loosening. Incomplete radiolucencies of < 1 mm developed in 3 additional femoral components at final followup. The incidence of tibial radiolucencies of 32% in the present study is similar to the incidence of radiolucencies with a nonstemmed revision cemented total knee arthroplasty, with the same prosthetic design, previously reported from the authors' institution.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7994948 TI - Noncemented revision total knee arthroplasty. AB - From 1985 to 1991, 16 patients underwent 17 revision total knee arthroplasties using porous-coated tibial or femoral components, or both, without cement. Eight knees had both components implanted without cement, 4 the femoral component without cement and 5 the tibial component without cement. Fifteen revisions were performed for aseptic loosening, 1 for instability, and 1 for infection. Patients were evaluated by clinical examination, radiographs, and the Hospital for Special Surgery Knee Rating Scale. Two patients died, leaving 15 revision total knee arthroplasties for followup. The average age at surgery was 65 years old. Followup averaged 5.6 years (range, 2.4-10.0 years). Range of motion preoperatively averaged 4 degrees to 96 degrees, and postoperatively 0 degree to 102 degrees. Average knee scores were 52 points preoperatively and 87 points postoperatively. Two tibial components showed lucent lines > or = 1 mm in 1 or more zones, 1 of which showed progressive lucencies. One femoral component showed a 1-mm lucent line in 1 zone, which was not progressive. Two tibial components were revised, 1 for a proximal tibial fracture below the prosthesis, and the other for prosthesis loosening and breakage. There was 1 stitch abcess with intrarticular extension, but no other infections. These results show that successful revision total knee arthroplasty can be accomplished using noncemented porous-coated components, with results comparable with those of cemented revisions. PMID- 7994950 TI - The effect of trochlear design on patellofemoral shear and compressive forces in total knee arthroplasty. AB - Biomechanical testing was performed on 5 cadaveric knees to evaluate the effect of patellofemoral design on shear and compressive force at the patellar component bone interface. Three patellofemoral designs with identical tibiofemoral articular surfaces were tested. The knees were tested under dynamic loading conditions from 0 degree to 100 degrees flexion. A transducer that measured 3 orthogonal force components was mounted between the patellar component and the patella. The combination of an oval dome patella with a 2-mm deeper trochlear groove and associated increased femoral resection was compared with a biconcave patella with standard trochlea and normal femoral resection. Alignment of the trochlear groove in 7 degrees valgus (anatomic) decreased medial-lateral shear by 10% to symmetric trochlear groove alignment. PMID- 7994951 TI - Impact of modern technique on long-term results of total condylar knee arthroplasty. AB - This study reports the 14-year survivorship for 106 consecutive total condylar knee arthroplasties implanted using modern technique. All were performed by a single surgeon and have been observed prospectively since 1979. Failure was defined as revision for any reason, or radiographic evidence of loosening of the components. Life-table analysis reveals a 95.6% clinical survival rate at 14 years, with no radiographically loose components. Confidence interval is +/- 4.2%. There were 4 revisions, but none for aseptic loosening, and there are no impending revisions. Thirty-seven patients (49 knees) were known to be deceased as of April 1993, and 8 other patients are lost to followup. Clinical results for patients with pre- and postoperative Hospital For Special Surgery knee scores show 72 knees rated excellent and 11 good (mean score, 90 points). The 4 failures were rated poor. Mean flexion was 100 degrees. Radiographs of 93 knees were evaluated using the criteria of the Knee Society. Average overall alignment was 5 degrees valgus. Radiolucencies were present in 29 of 78 femoral components with adequate radiographs, and averaged 1 mm in 1 zone. Tibial radiolucency was present in 42 of 93 tibiae, again averaging 1 mm in 1 zone, with no loose pegs. In comparison with the first series of total condylar prostheses, this series showed comparable clinical results, with improved radiographic results, and no radiographic failures. PMID- 7994952 TI - Long-term survival analysis of a posterior cruciate-retaining total condylar total knee arthroplasty. AB - From 1975 to 1983, 278 patients received 418 posterior cruciate ligament retaining Total Condylar knee arthroplasties. Twenty-four patients were excluded, 15 for lack of followup data, 6 for infection during followup, and 3 for revision surgeries for previous infections. The 394 remaining knees were observed from 1 to 18 years (mean, 8.08 years). Kaplan-Meier and crude survival estimates at 12 years were 96.8% and 98.1%, respectively. Various survival analyses by other authors have yielded similar successful results. PMID- 7994953 TI - Posterior cruciate supplementing total knee replacement using conforming inserts and cruciate recession. Effect on range of motion and radiolucent lines. AB - This study was performed to determine if a sagittally curved conforming tibial insert can be used with a retained, but balanced, posterior cruciate ligament without deleterious effects on range of motion (ROM) and tibial radiolucencies, as compared with a flatter insert that is less conforming and does not require cruciate balancing. The authors reviewed 50 consecutive primary knees implanted with flatter posterior lipped inserts and 50 consecutive primary knees with curved inserts and posterior cruciate ligament balancing. The average ROM for both groups was the same postoperatively as preoperatively: 111 degrees for the posterior lipped inserts and 113 degrees for the curved inserts. The incidence of tibial radiolucent lines was 8% for both groups. The authors conclude that sagittally curved, more conforming tibial inserts with retained, but balanced, posterior cruciate ligaments, do not adversely effect ROM and tibial radiolucencies. Their use forms an attractive compromise between the schools of cruciate preservation and cruciate substitution, maximizing their advantages while minimizing their disadvantages. Functional ROM can be achieved while bone stock is preserved, the joint line is restored, and wear characteristics are improved. PMID- 7994955 TI - Nonconstrained implants in revision total knee arthroplasty. AB - From March 1989 to March 1992, 39 knees were studied in 36 patients who had undergone revision total knee arthroplasty. A posterior stabilized modular prosthesis was used in 31 knees, and a standard condylar modular prosthesis was used in 8. Average followup was 20 months. The mean tibiofemoral angle was 2.1 degrees valgus (range, 22 degrees varus-23 degrees valgus) preoperatively, and 5.9 degrees valgus (range, 2 degrees varus-14 degrees valgus) postoperatively. Component placement in anteroposterior and lateral view was improved postoperatively. Postoperative patellar height was normal in 63.6% of the knees. Partial radiolucent lines were present in at least 1 prosthetic component in 72.7% of the knees, but no lines were complete. The Knee Society Pain Score improved from 50.5 points preoperatively to 82.7 points postoperatively. The Knee Society Function Score improved from 35.5 points to 56.1 points. Complications occurred in 20.5%. Since then, there has been 1 failure, an infection that subsequently led to knee fusion. Revision total knee arthroplasty presents difficult challenges, such as bone loss and ligamentous instability. A modular total knee replacement system allows the surgeon to do accurate preoperative planning and also to tackle unexpected problems intraoperatively. The authors' early results of revision total knee arthroplasty using a modular semiconstrained system are satisfactory. PMID- 7994954 TI - Effect of pegs and screws on bone ingrowth in cementless total knee arthroplasty. AB - The purpose of the present study was to assess the effects of pegs and screws on bone ingrowth into the tibial component in cementless total knee replacement. Left total knee replacements were performed in 21 mature male dogs with 3 cementless porous-coated tibial tray configurations (7 animals per group): (1) 4 peg design implanted with cortical screws passing through the pegs; (2) 4-peg design implanted without screws; and (3) pegless design secured by 4 cortical screws. The animals were allowed unrestricted activity and were euthanized 6 months postoperatively. The pegless components (Group 3) had the highest extent of bone ingrowth into the tray (90.3% +/- 9.4%), followed by the components with 4 pegs only (Group 2, 82.8% +/- 9.2%), and the components with 4 pegs and 4 screws (Group 1, 75.9% +/- 11.8%). The difference between Groups 1 and 3 was statistically significant (p < 0.05). The volume fraction of bone ingrowth in the tray did not differ among the 3 groups, with an overall mean of 22.5% (+/- 4.6%). At the posterolateral quadrant, Group 1 had significantly less bone ingrowth than Group 3 within the tray whether measured as the extent (63.6% +/- 20.5% versus 91.0% +/- 10.6%, p < 0.05) or volume fraction (19.1% +/- 8.8% versus 32.9% +/- 10.5%, p < 0.05). There were no between-group differences at the other quadrants. This study indicated that pegs provided no added benefit in a circumstance where sufficient initial fixation was obtained with screws. PMID- 7994956 TI - Resection specimen analysis of tibial coverage in total knee arthroplasty. AB - To maximize tibial coverage during total knee arthroplasty, a study was performed to evaluate the morphology of the proximal tibia at the resection level and assess tibial coverage with respect to existing tibial implants. Unmagnified radiographs of 42 tibial resection specimens were produced and digitized with existing tibial implants from the asymmetrical Genesis and the symmetrical Insall Burstein II and Press Fit Condylar total knee arthroplasty designs. The average total profile coverage ranged from 80.62% to 84.73%, whereas the average posteromedial coverage ranged from 76.05% to 82.09%. The shape of the tibia at the resection level was asymmetrical, and the overall tibial coverage was never greater than 85%. It appears that the actual shape of the tibial tray and the number of accommodating sizes provide the best ability of a total knee arthroplasty system to maximize tibial coverage, and not simply an asymmetrical or a symmetrical design. PMID- 7994957 TI - Simulated knee wear with cobalt chromium and oxidized zirconium knee femoral components. AB - A knee simulator that mimics the plowing/rolling wear mechanisms of the knee was used to compare wear properties of cobalt chromium and oxidized zirconium femoral components. The simulator flexes and extends the knee so that the femoral components travels from 0 degrees to 30 degrees while applying axial loads from 130 to 1300 lb. Three oxidized zirconium and 3 cobalt chromium femoral components were tested with 10-mm tibial polyethylene components. The oxidized zirconium femoral components caused significantly less ultra high molecular weight polyethylene wear than cobalt chromium femoral components. Tibial inserts that were articulated against the cobalt chromium components had evidence of scratching, burnishing, and delamination, but none of the surfaces that were articulated against oxidized zirconium components had evidence of delamination. Cobalt chromium surface roughness significantly increased during the 2,000,000 cycle test, but oxidized zirconium surface roughness was not affected. Polyethylene wear was correlated to a significant degree with the surface roughness of the femoral components. The improved wear characteristics of the ceramic articular surfaces can be explained by the wettability of the ceramic surface, which minimized adhesive wear, and the resistance of the hard, ceramic surface to roughening. PMID- 7994958 TI - Cementless total knee replacement. Nine- to 11-year results and 10-year survivorship analysis. AB - A pilot project was initiated in 1981 to evaluate cementless total knee arthroplasty. During the first 3 years, 265 Ortholoc I cementless femoral and tibial components were implanted in 202 patients. Sixty knees (39 patients) were lost to followup, and 31 knees (23 patients) were lost because the patients died, leaving 163 knees (129 patients) with 9- to 11-years' followup. One knee loosened during the 9- to 11-year followup period and was revised, and 5 knees were revised for infection. Considering loosening and infection, survival rate at 10 years was 96.7%. Five knees had revision of the patellar and tibial components for wear that began with the patella and later involved the tibial surface. Considering all modes of failure, survival rate at 10 years was 94%. Two years after surgery, 83.0% of patients had no pain, 15.2% had mild pain, 1.8% had moderate pain, and none had severe pain. Five years after surgery, 77.9% of patients had no pain, 12.1% had mild pain, 6.0% had moderate pain, and 4.0% had severe pain. Ten years after surgery, 83.7% of patients had no pain, 6.1% had mild pain, 8.2% had moderate pain, and 2.0% had severe pain. Knee flexion was 110 degrees preoperatively and increased to a mean of 115 degrees at 2 years postoperative, then remained unchanged for the remainder of the followup. Cementless total knee replacement was a reliable and effective means of treating the end-stage arthritic knee. In knees that required revision, excellent bone stock remained and cementless revision was easily accomplished. PMID- 7994959 TI - Translation of the glenohumeral joint with simulated active elevation. AB - Translation of the glenohumeral joint was measured with a dynamic shoulder model during elevation of the arm in 8 cadaveric specimens. Controlled hydrodynamic actuator forces were applied to the deltoid muscle and the rotator cuff through wire cables. Using a constant force ratio, the glenohumeral joint was elevated to 90 degrees. The position of the arm in all spatial orientations was measured with an ultrasonic device. Reproducibility of glenohumeral joint motion was demonstrated on the basis of 5 cycles of glenohumeral joint elevation. The rotational center of the humeral head was used as the reference point for translation. Translation during elevation of the glenohumeral joint between 20 degrees and 90 degrees averaged 9.0 mm +/- 5.2 mm superiorly and 4.4 mm +/- 1.3 mm anteriorly. Physiologic variation of muscle activity, which is not yet fully understood, was not included in the model. In vivo, translation may be diminished by coordinated activity of the rotator cuff. The presence of significant glenohumeral joint translation underlines the importance of active, muscular guidance at the shoulder. Physiologic translation must be considered in the design of total shoulder arthroplasty, in shoulder instability, and in the impingement syndrome. PMID- 7994960 TI - Analysis of the bone surface area in resected tibia. Implications in tibial component subsidence and fixation. AB - Anterior subsidence of the tibial component is still a clinical complication requiring revision in total knee replacement. Using the scanning electron microscope, a quantitative 3-dimensional stereoscopic and digitizing study was conducted on the cortical and cancellous bone surface area from 10 resected human cadaveric tibia. The data demonstrated that the cortical bone surface area covered an average of 6% of the total tibial surface area, cancellous bone 18%, and bone marrow space 76%. By conducting anatomic regional analysis, the data showed significantly higher (p < or = 0.05) bone quantities in the posteromedial and medial regions as compared with the anterior and anterolateral regions. These data help to explain why tibial component subsidence occurs anteriorly in total knee replacement. The data also suggest that if long-term component subsidence and loosening is to be limited, either biologic cement or bone cement would be required to increase the surface attachment between the tibial component and resected cancellous bone. PMID- 7994961 TI - The natural history of ultra high molecular weight polyethylene. AB - Degradative changes occurring during the lifetime of ultra high molecular weight polyethylene total joint components made from 2 different starting resins were determined from retrieved tibial inserts. The inserts were manufactured in the Department of Biomechanics of the authors' institution, for intrahospital use by the hospital's surgical staff, allowing the ultra high molecular weight polyethylene properties to be traced from production, to sterilization, to shelf life, and to subsequent retrieval. Changes were found in the density and the infrared spectra. Density was greater after sterilization and at retrieval, when compared with the density of the virgin ultra high molecular weight polyethylene material, with a greater increase near the surfaces than within the bulk of the inserts. The inserts that had the longest life-times demonstrated the greatest increase in density. Density increases are important because they reflect increases in the elastic modulus of the ultra high molecular weight polyethylene. Such increases near the articulating surface of a total joint component would cause significant increases in the stresses associated with wear damage occurring on and near these surfaces. The infrared spectra were consistent with oxidative degradation. PMID- 7994962 TI - The pedicle latissimus dorsi transfer for reconstruction of the plexus brachialis and brachium. AB - To reconstruct the area from the brachial plexus to the upper arm, pedicle latissimus dorsi muscle transfer was performed in 16 patients. Nine patients underwent functional bipolar transfer for reconstruction of elbow flexion. The surgical results were satisfactory in 6 patients, but were unsatisfactory in 3 because of an incorrect preoperative assessment of the strength of the latissimus dorsi muscle and an unsuitable length of transferred muscle in 2 patients, and because of progression of spastic paralysis caused by cervical myelopathy in the third patient. Seven patients with skin loss and an unstable scar underwent aesthetic unipolar transfer in which the exposed nerve, neurovascular bundle, bone, and joint were covered by a musculocutaneous flap with good vascularity. The surgical results were successful in all 7 patients. Infection was present before transfer in 4 of the 16 patients, but it was successfully treated by simultaneous radical debridement of the infected wound and latissimus dorsi transfer. PMID- 7994963 TI - Fracture at the iliac bone graft harvest site after fusion of the spine. AB - To determine the clinical features of iliac crest graft harvest site fracture after spinal arthrodesis, a retrospective study surveying the spinal surgery performed at Case Western Reserve University was performed. Approximately 200 cervical spine fusions and an equal number of lumbar spine fusions are performed in that center each year. Between November 1985 and March 1991, 14 patients were identified with fractures at an iliac crest graft harvest site. All but 1 of these patients were female. They had an average age at surgery of 61 years old (range, 24-76 years old). Twelve patients had cervical procedures (2 posterior and 10 anterior fusions). The patients with anterior cervical fusions experienced avulsion fractures of the anterior superior iliac spine. One patient with a posterior occipital cervical fusion experienced bilateral posterior iliac wing fractures, and 1 with posterior atlantoaxial fusion resulted in a unilateral iliac wing fracture. All patients were treated nonoperatively with protection of weight bearing until resolution of pain. All patients had satisfactory results at final followup ranging from 6 months to 5 years. Three patients had residual mild pain that did not affect activities of daily living. The remainder were pain free. Few series of fractures of the pelvis after graft harvest are reported. This group of patients had satisfactory results with nonoperative treatment. Older female patients with osteopenic bone are prone to iliac graft site fracture, and particular care should be exercised in this population. PMID- 7994964 TI - Periprosthetic bone mineral density after Mueller and Zweymueller total hip arthroplasties. AB - To assess the adaptive bone changes in adult human hips after insertion of cemented or uncemented acetabular and femoral components for total hip arthroplasty, a retrospective clinical study using dual energy xray densitometry was conducted. A consecutive homogeneous group of 52 female patients with an average age of 61 years was operated on for unilateral hip osteoarthritis. The types of prosthetic components used were the cemented Mueller and the uncemented Zweymueller socket and stem. Periprosthetic bone mineral density was measured in 7 different zones (Zones I to VII) in hips that were operated on and hips that were not, and the results were compared to quantify periprosthetic bone mineral changes over time. The Zweymueller socket induced bone resorption at the medial and caudal zone of the acetabulum, whereas implantation of the Mueller polyethylene socket was associated with a significant increase in bone mineral density only at the cranial zone of the acetabulum. The stem of the Mueller prosthesis induced bone mass reduction in the lesser trochanter area and in the distal lateral fixation cortex. The Zweymueller stem produced significant bone resorption in the area of the lesser trochanter, and in the medial and lateral distal cortex of the femur. The Mueller and Zweymueller stems induced bone mass increase in the greater trochanter area. These findings were unaffected by the age of the patients. Further improvement in densitometry technology may be of major clinical relevance for early detection of aseptic loosening in total hip arthroplasty. PMID- 7994965 TI - Femoral lengthening by callus distraction and cortical apposition (Z-osteotomy). AB - Nine patients underwent femoral lengthening by callus distraction with cortical apposition (Z-osteotomy). The average amount of lengthening was 4.8 cm (range, 2.9-6.0 cm). The average time of external fixator use was 70 days (range, 33-100 days). The average time for using the cast brace was 3.5 months. All patients had complete union. No patient required bone grafting. No patient had premature consolidation of the osteotomy. Complications included cellulitis around the pins in 2 patients, transient peroneal nerve palsy in 1 patient, and fracture after removal of external fixator in 2 patients. In this procedure the alignment and rotation is controlled by a strong external fixating device. The large area of cortical contact after z-osteotomy assists in rapid union of the distracted bone. PMID- 7994966 TI - Arthroscopic treatment of intraarticular fibrous bands after total knee arthroplasty. A followup note. AB - Eighteen consecutive patients (average age, 66.4 years at arthroscopy) who had a previous total knee arthroplasty underwent arthroscopic resection of a transverse suprapatellar fibrous band, which was causing patellar snapping and jumping as it impinged on the intercondylar notch portion of the femoral component during active extension (tethered patellar syndrome). Fourteen patients were available for followup at an average of 56 months (range, 37-91 months). All patients had complete relief of the patellar symptoms. One patient had a recurrence of symptoms 10 months after arthroscopy but remained symptom free 30 months after repeat resection. All are currently symptom free and are classified as having excellent results. The average range of motion is 1 degree to 115 degrees. There were no complications attributable to the arthroscopy. The tethered patellar syndrome has been noted by various authors, and has been most commonly treated by arthrotomy. At arthroscopy, a transverse suprapatellar fibrous band was seen to catch on the intercondylar notch of the femoral component, snapping free as the knee extended past approximately 30 degrees. In this population, excellent long term results were achieved with arthroscopic removal of the transverse suprapatellar band. PMID- 7994967 TI - Relationship between osteofibrous dysplasia and adamantinoma. AB - The records and computer files of 32 patients treated at 1 institution for ossifying fibroma, fibrous dysplasia, osteofibrous dysplasia-like adamantinoma, or adamantinoma of the tibia were reviewed. Nineteen patients had their diagnosis changed, either because of a recurrence or through review of their histology. Six of the 9 patients who had a typical adamantinoma and 6 of the 10 patients who had an osteofibrous dysplasia-like adamantinoma had a diagnosis of 1 of the benign conditions before their adamantinoma was recognized. Only 6 patients actually had osteofibrous dysplasia. Three patients required a resection, but only 1 of the other 3 has been observed > 5 years. This review suggests that many patients with a diagnosis of fibrous dysplasia or osteofibrous dysplasia of the tibia actually have an adamantinoma, and that osteofibrous dysplasia is often a locally aggressive lesion that progresses until it is widely resected. In addition, osteofibrous dysplasia and adamantinoma appear to be related, and osteofibrous dysplasia may be a precursor of adamantinoma. PMID- 7994968 TI - Biomechanical simulation of the anteroposterior compression injury of the pelvis. An understanding of instability and fixation. AB - Seven fresh cadaveric pelvic specimens were biomechanically analyzed. Testing was first performed on intact pelves and then after progressive disruption of the (1) symphysis pubis, (2) unilateral anterior and interosseous sacroiliac ligaments and capsule, (3) ipsilateral sacrospinous and sacrotuberous ligaments; and fixation with a 4.5-mm narrow dynamic compression plate at the symphysis pubis, or a 4.5-mm narrow dynamic compression plate at the anterior sacroiliac joint with and without the symphysis pubis plate, or a 7.0-mm sacroiliac lag screw anchored into the S1 vertebral body with and without the symphysis pubis plate. Symphyseal gapping occurred after isolated symphysis pubis disruption. With additional disruption of the unilateral sacroiliac joint ligaments, symphysis pubis displacement was unaffected; however, the injured sacroiliac joint gap displacement, and sacroiliac joint flexion angulation on both intact and injured sides increased as compared to the specimen in the intact state. Further disruption of the ipsilateral sacrotuberous and sacrospinous ligament complex produced little additional motion at either symphysis pubis or sacroiliac joints. Plate fixation of the symphysis pubis alone reduced symphysis pubis motion, but not sacroiliac motion. Use of sacroiliac fixation alone without a symphysis pubis plate did not affect symphysis pubis motion. The symphysis pubis plate is the key to stabilizing symphysis pubis motion, and similarly, sacroiliac joint fixation is required to control sacroiliac joint motion. Both single iliosacral screws and plates produced equivalent decreases in sacroiliac joint motion. PMID- 7994969 TI - Mechanical performance of the Monticelli-Spinelli external fixation system. AB - Six configurations of the Monticelli-Spinelli external fixator were tested for axial compression, bending, and torsion. The ring wire clamp unit was separately tested under repeated cyclic loading and retightening of the clampnuts. The configurations studied were the following: 3 standard (4-ring and 3-ring with 5 mm between the wires and 3-ring with 40 mm between the wires); and 3 hybrid (3 ring and 1 pin, and 2-ring and 2 pins with the rings either placed closer or distant to the fracture). For each configuration, 5 frames were constructed. Axial stiffness was nonlinear for both fixator types. Four-ring fixators and 2 ring 2-pin fixators had similar stiffness, yet were stiffer than 3-ring configurations. Anteroposterior bending stiffness was highest in the 4-ring configurations, whereas oblique bending for standard fixators was similar to lateral bending stiffness for the hybrid configurations. Torsion was higher in the 4-ring construction and in hybrid frames compared to the standard 3-ring frames. For the ring wire clamp unit, stiffness increased and hysteresis diminished after each retightening of the clampnuts because of the increase of contact between clamps and ring. The hybrid configurations provide an alternative that enables more simple configurations with less transfixing elements and sufficient stiffness. PMID- 7994970 TI - Useful hints for the study of the history of orthopaedics. AB - Although there is considerable interest among orthopaedic surgeons in the history of their specialty, many fail to pursue their interest because of an unfamiliarity with the tools and methods by which historical information can be assembled. The purpose of this article is to point out the resources for historical research available to most physicians and to give some suggestions for their use. PMID- 7994971 TI - Knee pain in a 28-year-old man. Chondrosarcoma, grade II. PMID- 7994972 TI - A combined laboratory and clinical analysis to evaluate a new tendo-Achilles repair technique. PMID- 7994973 TI - A biochemical, histologic, and immunohistologic analysis of membranes obtained from failed cemented and cementless total knee arthroplasty. PMID- 7994974 TI - Tibial component wear in total knee replacement. AB - Polyethylene wear is currently 1 of the major problems of total knee replacement. Evaluation of a large number of revised tibial components showed 3 wear patterns. Symmetrical central and symmetrical posterior wear are rare. Asymmetric wear beginning at the posteromedial part of the tibial plateau is the common pattern. The first step in the main wear process is cold flow of the polyethylene of the posteromedial part of the tibial plateau. The horizontal axis of rotation becomes fixed by this plastic deformation, and wear of the posteromedial part of the plateau then ensues. The vertical axis of rotation also becomes trapped, resulting in external rotation of the tibia on the femur leading to maltracking, exacerbating the wear and leading to an increased volume of wear debris, which eventually leads to chronic synovitis and osteolysis. Wear is more pronounced in the thinner units. Absence of a cruciate gap seems to prevent the initial cold flow and thus minimizes wear. PMID- 7994975 TI - Tibial osteolysis in cementless total knee arthroplasty. A review of 25 cases treated with and without tibial component revision. AB - Revision total knee arthroplasty was performed in 25 knees with tibial osteolysis that was identified radiographically and confirmed histologically. Eighteen knees had focal osteolysis in the medial tibial plateau, 2 in the lateral plateau, and 5 in both plateaus. Three surgical treatment options were used: (1) exchange of the modular tibial polyethylene insert with screw removal; (2) revision of the tibial component with curettage and optional grafting of the defect; (3) and full revision of all components. The clinical and radiographic results of partial and full revision remain excellent 2 to 6 years (mean, 41 months) postrevision arthroplasty for 23 knees. Clinical failure with pending revision occurred in 1 patient with polyethylene exchange without the removal of tibial fixation screws, and in 1 patient with progression of osteolysis adjacent to the femoral component 2 years after tibial component revision. Tibial defects have not progressed, and new lesions have not developed with simple curettage of the defect and removal of sources of particulate. Tibial baseplates remain radiographically stable. Component revision of the tibial component, femoral component, or both, required the insertion of long-stemmed revision components and frequently the use of major structural allografts. These revisions have faired well, although the long-term stability of components supported with major structural allografts is unknown. PMID- 7994976 TI - Treatment of the infected total knee arthroplasty with insertion of another prosthesis. The effect of antibiotic-impregnated bone cement. AB - Eighty-six patients with 89 infected total knee arthroplasties were treated with insertion of another prosthesis. Treatment was not according to an established protocol for parameters, such as delay between removal of the infected prosthesis and insertion of the new prosthesis, duration of antibiotics, use of antibiotic impregnated cement spacers or beads, and use of antibiotic-impregnated cement for prosthetic fixation at revision surgery. Final followup averaged 52 months (range, 6-126 months). Complications occurred in 30 (33.7%) knees, with recurrent deep infection developing in 10 (11.24%) knees. Patient age, medical diagnosis, type of microorganism, duration of parenteral antibiotics, delay between the resection and revision surgery, and use of antibiotic-impregnated cement spacers or beads were not correlated with the cure rate of infection. Use of antibiotic impregnated bone cement for prosthesis fixation at revision surgery was the only variable that correlated with the cure rate of deep infection. Seven (28%) of the 25 knees without antibiotic-impregnated cement for prosthesis fixation developed recurrent infection compared with 3 (4.7%) of 64 knees with antibiotic impregnated cement for prosthesis fixation. This difference was statistically significant (p = 0.0025, log-rank test). PMID- 7994977 TI - Patterns of knee arthrosis and patellar subluxation. AB - This study was based on the unexpected observation of lateral patellofemoral subluxation in the varus osteoarthritic knee. Standardized radiographs of 109 knees (65 patients with osteoarthritis) were selected randomly from the authors' database and retrospectively reviewed. Hip-knee-ankle alignment data were correlated with patellofemoral subluxation and tilt, as well as with radiographic patellofemoral grades for arthrosis. The amount and site of patellofemoral arthrosis were correlated with patellar position and limb alignment. Patellae that were located centrally in the trochlear groove had the lowest radiographic score for arthrosis. Subluxation of the patella, either medially or laterally, was correlated with increased radiographic scores. Limb alignment was not correlated with the radiographic score. A significant percentage of varus knees (28%) had unexpected lateral subluxation of the patella. This observation has not been reported previously. It may have an impact on surgical decision-making for total knee arthroplasty and osteotomy. PMID- 7994978 TI - The posterior cruciate ligament in total knee surgery. Save, sacrifice, or substitute? AB - To determine the role of the posterior cruciate ligament in total knee arthroplasty, 242 consecutive primary total knee arthroplasties were included in 1 of 3 sequential groups. Group I included 77 Press Fit Condylar total knee replacements in which the posterior cruciate ligament was completely released from its tibial attachment. In Group II, there were 80 Press Fit Condylar total knee replacements in which the posterior cruciate ligament was retained. Group III consisted of 85 total knee replacements with a posterior cruciate substituting device (Insall-Burstein II). All patients were observed at least 2 years and evaluated by the Knee Society's Clinical and Functional Scoring System, including a radiographic evaluation. No differences were found between the posterior cruciate ligament sacrificed group and the posterior cruciate ligament preserved group. The 1 significant difference among the 3 groups was in range of motion (ROM). Groups I and II averaged 103 degrees and 104 degrees motion respectively, whereas Group III, the posterior cruciate-substituting group, averaged 112 degrees (p = 0.001). In addition, only in Group III was the lower 95% confidence limit of the mean ROM > 90 degrees. These findings suggest that preserving the posterior cruciate ligament does not consistently lead to improved functional ROM. The posterior cruciate ligament-substituting device historically has demonstrated excellent survivorship and appears to offer greater ROM. PMID- 7994979 TI - Comparison of interface membranes obtained from failed cemented and cementless hip and knee prostheses. AB - Biochemical and histologic analyses were performed on interface membranes obtained at revision of aseptically loosened hip implants (n = 36) and knee implants (n = 16). Clinical failure occurred sooner in patients with uncemented total hip implants (Group 1) than in patients with cemented implants (Group 2) (p < 0.02). There was no difference in time to revision between the patients with uncemented implants (Group 3) and patients with cemented total knee implants (Group 4). Histologically, more small (< 5 mu) polyethylene particles were found within macrophages and fibroblasts in membranes from Groups 1 and 2. Polyethylene particles from failed total knees (> 10-100 mu) were larger than those from failed total hips. Large polyethylene fragments and foreign-body giant cells were more common in failed knees than failed total hip membranes. Biochemically, proteinase and cytokine activity in the tissue culture supernatant from all groups was higher than in the control tissue (p < 0.01). The activities of stromelysin, prostaglandin E2, interleukin-1 alpha, interleukin-1 beta, and tumor necrosis factor-alpha were higher in Groups 1 and 2 than in Groups 3 and 4 (p < 0.05). These findings support the hypothesis that interface membranes enveloping femoral (hip) and tibial (knee) components of failed total joint implants may promote bone resorption and aseptic loosening. The reason for slower failure of knee implants as compared with hip prostheses may be the lower level of biochemical activity and macrophage density that correlates closely with larger polyethylene particles. PMID- 7994980 TI - Posterior cruciate ligament strain biomechanics in total knee arthroplasty. AB - To evaluate the role of the posterior cruciate ligament in total knee arthroplasty, 8 normal whole-leg cadaveric legs were studied. Strain patterns of the posterior cruciate ligament were measured during active and passive knee flexion extension. Total knee arthroplasty was performed, and posterior cruciate ligament strain was measured again. The standard tibial insert was removed, and 3 additional tibial trays were used: flat, 10 degrees sloped, and 15 degrees sloped. The posterior cruciate ligament strain was recorded for each tibial insert. Total knee arthroplasty with a standard insert produced a large range of posterior cruciate ligament strain values (+/- 6%). Of the 8 specimens, 3 produced excessively taut posterior cruciate ligament strain, 3 were slack, and 2 returned strain to the baseline strain value. Changing the surface contour and slope of the tibial inserts did not produce any consistent change in the posterior cruciate ligament strain pattern. The ability of total knee arthroplasty to reproduce normal posterior cruciate ligament strain behavior has not been demonstrated. PMID- 7994981 TI - One-stage versus 2-stage bilateral total knee arthroplasty. AB - This retrospective study reviews 155 bilateral total knee arthroplasties, of which 99 were simultaneous and 56 staged. The results revealed that blood loss and postoperative blood requirements were higher in the simultaneous group, with 60% requiring homologous blood. The simultaneous approach was advantageous for a reduction in hospital stay, physical therapy, and resultant hospital costs. The complication rate was similar for both groups when examining pulmonary embolism, wound problems, infection, deep venous thrombosis, and death. The authors' incidence of fat embolism syndrome was similar for both groups but higher than that reported in the literature. Attempts with present preoperative evaluation cannot predict the incidence of fat embolism syndrome. A more invasive preoperative workup may identify those at risk. Preoperative marrow stimulants and the use of reinfused blood may eliminate the use of homologous blood in the simultaneous group. PMID- 7994982 TI - [Antiplatelet therapy in patients with cerebral thrombosis at the chronic phase- assessment of its effect on coagulation and fibrinolytic parameters]. AB - We studied the effect of antiplatelet therapy not only on the secondary prevention of stroke but also on the suppression of vascular damages in patients with cerebral thrombosis at the chronic phase. We measured von Willebrand factor (vWF) as a marker for the endothelial system, and coagulation and fibrinolytic parameters in addition to platelet functions. The platelet aggregation and markers for platelet activation were monitored for the adequate inhibition of platelets. Twenty-one patients were treated with 200 mg ticlopidine. 9 patients with 100 mg ticlopidine and 60-150 mg acetylsalicylic acid, and 18 patients with 200 mg cilostazol daily. The mean duration of follow up was 8.4 +/- 3.0 months. A patient was attacked by a recurrent stroke, but no fatal vascular events occurred during the period. A significant decrease was observed in the collagen- and ADP induced platelet aggregation and markers for platelet activation such as platelet factor 4 (PF4) and beta-thromboglobulin (beta TG) by the antiplatelet therapy. In addition, the activities of coagulation factor VIII (FVIII) and vWF, markers for vascular damages, showed a significant decrease. The results suggest that the antiplatelet therapy could ameliorate the vascular damage through the inhibition of platelet function. Moreover, thrombin-antithrombin III complex (TAT) and alpha 2-plasmin inhibitor-plasmin complex (PIC), markers for the activation of coagulation and fibrinolytic systems, decreased significantly, suggesting that the treatment inhibits the activation of coagulation and fibrinolytic systems induced by the platelet activation. The activities of FVIII and vWF decreased significantly when the level of beta TG or that of PF4 lowered sufficiently by the treatment.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7994983 TI - [Influence of age on long-term memory]. AB - Memory for past public events having occurred between 1950-1989 was examined in Japanese subjects with average education aged forty to seventy-nine years. We compiled a public events test battery consisting of 80 multiple-choice questions regarding events, persons, or places that were prominent in the news during the four decades 1950 to 1989. With increasing age, performances of a public event test declined equivalently each decade. The effect of both age and decade was significant by three-way analysis of variance. The interaction term (age x decade) was not significant, which indicates that performance on questions relating to each decade was affected about equally by age. Performance on this test was clearly age-dependent across the time period sampled. Considering the results obtained in this study, we could conclude that aging influences very old memories as well as recent memories. PMID- 7994985 TI - [IgG subclasses in the patients with myotonic dystrophy]. AB - Low serum concentration of IgG in myotonic dystrophy (MyD) has been well documented and has been considered to be due to accelerated breakdown of IgG. However, the catabolic rate of IgG is tightly regulated by serum IgG level and basal metabolic rate. The serum IgG level and basal metabolic rate in the patient with MyD is reported to be significantly low. One possible explanation for this fact is presence of disproportion in IgG subclasses; if the level of one or some subclasses is high, catabolism of total IgG could be accelerated regardless of decreased total IgG. In this study, we examined serum concentration of all four IgG subclasses by sandwich ELISA methods in 43 patients with MyD and 24 healthy age- and sex-matched controls. Serum levels of al IgG subclasses were lower in MyD than those in normal controls, especially the levels of IgG1 and IgG3 were significantly low (p < 0.01) as compared to those in normal controls. These results, combined with our previous studies, suggest that accelerated catabolism is inadequate as a cause of low serum concentration of IgG in MyD. Further studies are required to approach the mechanism of low serum concentration of IgG in the patients with MyD. PMID- 7994984 TI - [Significance of rimmed vacuoles in neuromuscular disorders--a comparative immunohistochemical study of inclusion body myositis and distal myopathy with rimmed vacuole formation]. AB - Of 3,403 muscle biopsies from patients with a variety of neuromuscular disorders, 87 (2.6%) had at least three muscle fibers with rimmed vacuoles in a single low power field (magnificantion x 20). The rimmed vacuole formation may be a crucial pathologic findings to understand the pathogenesis of inclusion body myositis (IBM), distal myopathy with rimmed vacuole formation (DMRV), Marinesco-Sjogren syndrome and oculopharyngodistal myopathy, because the muscle fibers in these biopsies showed no striking necrotic and denervating changes. Since Congo red positive material and ubiquitin- and beta-amyloid protein-positive deposits were found in muscle fibers with rimmed vacuoles in DMRV and various neuromuscular disorders besides IBM, these findings may have no disease-specific significance and may be not helpful in differentiating DMRV from IBM. PMID- 7994986 TI - [Clinical study of platelet activation in cerebral circulation--comparison between ischemic stroke subtypes and Binswanger's disease]. AB - To elucidate platelet activation in cerebral circulation and its significance in ischemic stroke, the plasma beta-thromboglobulin (BTG) concentration gradients between the internal jugular vein and the antecubital vein were investigated in 164 patients with ischemic stroke. They consisted of cases of lacunar, atherothrombotic, cardioembolic stroke, and Binswanger's disease. The diagnosis of each stroke category was based on both computed tomographic (CT) and clinical findings. In particular, Binswanger's disease was diagnosed by the diagnostic criteria proposed by Bennett et al. Blood was withdrawn simultaneously from the internal jugular vein (A) and the antecubital vein (B) followed by determination of the BTG-A level and the BTG-B level, respectively. The BTG levels of 184 paired blood samples, thus, were obtained and the ratio (delta BTG) of BTG-A/BTG B was calculated as an indicator for platelet activation in the cerebral circulation. According to the timing of the examination, these values of the acute phase less than 7 days after the event were separated from those of the chronic phase more than 28 days after the event. The delta BTG levels were also determined in 25 of controls with diseases other than stroke and considered to reflect platelet activation in the cerebral circulation. The mean delta BTG values of each stroke subtype without ticlopidine treatment, compared with those of controls (0.96 +/- 0.42), were significantly higher except those during the chronic phase of cardioembolic stroke and pronounced variability of delta BTG was noted in most subtypes.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7994987 TI - [Recurrence and prognosis in ischemic stroke patients with anticardiolipin antibody in Japan]. AB - Anticardiolipin antibody (aCL) is considered to be one of the contributory factors in the development of cerebral infarction. We compared the recurrence and prognosis of 20 ischemic stroke patients with positive IgG aCL who had no collagen vascular diseases with those in 120 patients with negative IgG aCL. The aCL-positive patients comprised 18 females and 2 males aged 43-79 (mean 64) years and the mean follow-up period was 5.6 years. The aCL-negative patients comprised 82 males and 38 females aged 40-84 (mean 64.2) years and the mean follow-up period was 5.8 years. There was no significant difference in age and mean follow up period between the two groups. We examined the recurrence rate and the intervals from the onset to the recurrence in both groups. We investigated the relationship between the recurrence of stroke and chronological changes in titer of aCL in patients with positive aCL. We also evaluated the effectiveness of antiplatelet agents for the prevention of recurrent stroke in both groups. A positive aCL level was defined as one which was > 3 standard deviations (S.D.) above the mean level for normal controls. A high titer of aCL was defined as being > 7 S.D. above the normal mean value. Among the 20 patients with positive aCL, recurrence of ischemic stroke occurred in 10 (50%) (cerebral thrombosis in 8 and cerebral embolism in 2) and myocardial infarction developed in 2 patients. As regards the number of ischemic episodes of stroke, recurrence occurred twice in 4 and once in 6 patients.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7994988 TI - [Involuntary movements caused by thalamic lesion]. AB - We described two types of involuntary movement accompanied with a well-located thalmaic lesion shown by MR imaging in five patients. All patients had the involuntary movements of an upper limb contralateral to the thalamic lesion. Two patients (1 and 2) had choreoathetosis that became most prominent when their index finger approached their nose, where irregular and dysynchronous oscillation occasionally superimposed. This choreoathetosis was differentiated from pseudoathetosis caused by disturbance of proprioceptive sensations. The MRI lesion was located at the middle level of thalamus including nucleus centromedianus. The other three patients (3, 4 and 5) had a regular and rhythmic oscillation in their forearm. The oscillation began to appear after their index finger reached their nose on finger-to-nose test. We considered the oscillation as a postural tremor based on its rhythmicity and regularity. Patient 4 had additional tremor in movement. Their postural tremor continued while the arm kept the position. Surface electromyogram showed the reciprocal discharges between the forearm extensor and flexor muscles with a frequency of 3 to 4 Hz. This tremor was not accentuated during limb movement toward the nose nor was coarse, and was distinguished from intention tremor described by Charcot and Dejerine. This tremor was also different from hyperkinesis volitionnelle and movement oppositionist. The "rubral tremor" differed from the tremor shown in our cases for a lack of resting tremor. The responsible lesion shown by MRI located at caudal posterior thalamus including pulvinar in patient 3, or located at the upper level of thalamus in patient 4 and case 5 that was more rostral than the lesion of the choreoathetosis cases. In cases of cerebrovascular accidents, both types of involuntary movement appeared after several months from the stroke. This delayed appearance suggests that these involuntary movements were the result not only of functional disturbance of thalamus, but of secondary repairing mechanism occurring at the lesion. PMID- 7994990 TI - [A case of Rendu-Osler-Weber disease with brain hemorrhages and portal-systemic encephalopathy]. AB - A 64-year-old woman was admitted because of abnormal behaviors. She had previous histories of recurrent epistaxis for 20 years and brain hemorrhages at the age of 51 and 58 years old. Her elder sister had episodes of recurrent hematemesis and telangiectasias of finger tips. Physical examination revealed multiple small telangiectasias of the tongue and finger tips. Flapping tremor of the upper extremities was seen. Laboratory examinations demonstrated hyperammonemia and an electroencephalogram showed triphasic waves compatible with hepatic encephalopathy. Angiographic studies revealed dilated hepatic arteries with early filling of hepatic veins. We made a diagnosis of Rendu-Osler-Weber disease (ROW disease) based on cutaneous telangiectasia, her previous history of repeated epistaxis, and a positive family history. We speculated that hepatic encephalopathy in the present case was caused by porto-systemic shunt due to ROW disease, and that recurrent brain hemorrhages had resulted from rupture of telangiectasias of the brain vessels. PMID- 7994989 TI - [Increased unilateral central motor tract excitability in a patient with corticobasal degeneration]. AB - In a 64-year-old woman with a clinical diagnosis of corticobasal degeneration, a hyperexcitability of central motor tract was demonstrated. She had akinesia, regidity, myoclonic movement, hyperreflexia, forced grasping and clumusiness on the right extremities. The asymmetry of these symptoms was striking. Dopa therapy was not effective. On single photon emission computed tomography (SPECT), blood perfusion was reduced especially on the left side in the frontoparietal area. She had large C-reflex after the median nerve stimulation only on the affected side. The intensity threshold of motor evoked potential by stimulation on the left motor cortex was lower than that on the right motor cortex. Conditioning stimulation of the median nerve on the affected side, greatly increased MEP size as compared to those of normal subjects, at conditioning-test (C-T) intervals of 40-80 ms; whereas, stimulation on the contralateral side did not. On the other hand, SEP did not have a marked increase or asymmetry in size and SEP recovery curve showed no hyperexcitability. These results indicate there is a hyperexcitability of the central motor tract on the affected side. PMID- 7994991 TI - [123I-IMP SPECT findings of visual perseveration in a patient with old hemorrhage in the right occipital lobe]. AB - We report a case of visual presevertation in a 67-year-old man. He had been well until 66 years of age when he had brain hemorrhage in the right occipital lobe. After an operation for removal of the hematoma, visual hallucination occurred and persisted for about 6 months. One year and a half later, he had a convulsive seizure and diphenylhydantoin was started. During the two weeks following the convulsion, he several times experienced episodes of visual preservation, visual hallucination and metamorphopsia. MRI revealed an old hemorrhage in the right occipital lobe. 123I-IMP SPECT demonstrated increase of cerebral blood flow of the right medial occipital lobe one day after the episode of visual perseveration and decrease about three weeks after the episode. The mechanism which causes visual perseveration still remains to be clarified. The findings of 123I-IMP SPECT of the present case suggest that visual perseveration may be generated by postictal transient functional excitation of the right occipital lobe. PMID- 7994992 TI - [A case of glycogen storage disease with normal acid maltase accompanied with the abnormal platelet function]. AB - Glycogen storage disease with normal acid maltase first reported by Danon et al. was characterized clinically by mental retardation, cardiomyopathy, and proximal myopathy. Since the first report, 17 patients have been reported including 5 patients from Japan. In this paper we described a 26-year-old man who had dilatated cardiomyopathy with a pacemaker implanted at age 22 years. He was admitted to our hospital complaining of easy fatigability in February 1992. Neurological findings showed that he had mental retardation. Serum CK, GOT, GPT and aldolase levels were elevated. Histopathological study of biopsied skeletal muscle showed intracytoplasmic vacuoles with increased acid phosphatase and slightly increased PAS positive material. Electron microscopic study revealed numerous glycogenosomes (autophagic vacuoles containing glycogen). These pathological findings were similar to acid maltase deficiency, but activities of carbohydrate metabolic enzyme including acid maltase activity were normal in the biopsied muscle. From these results, he was diagnosed as having glycogen storage disease with normal acid maltase. We also found abnormal platelet function and glycogen accumulation in the platelets, which have not been previously described. The disease is probably a systemic disorder affecting not only skeletal and cardiac muscles, but platelets. PMID- 7994993 TI - [An unusual case of status epilepticus of simple partial seizure with an occipital lobe focus]. AB - A 45-year-old man developed generalized convulsion and consciousness disturbance at age 43. An X-ray CT revealed hemorrhagic infarction in the left fronto-parieto temporal area. A conventional angiography disclosed complete occlusion of the left cortical vein. In the chronic stage of the stroke, he had incomplete right quadrantopsia, a mild right hemiparesis and sensory aphasia. The patient has had partial somatosensory seizures since February 1990. Ictal EEG recordings showed epileptogenic discharges in the left parietal region. The seizures were adequately controlled with clonazepam. Since July 27, 1993, he has become aware of blurred vision in both eyes accompanied with headache and dizziness. On August 6, he was admitted to the hospital with right homonymons hemianopsia, sensory aphsia and tonic seizures in the right hand. Ictal EEG recordings demonstrated theta waves of the left parieto-occipital region and epileptogenic discharges in the left occipital region which consisted of spikes, sharp waves and spike-wave complexes. Single photon emission computed tomography (SEPCT) images obtained during seizures showed considerable hyperperfusion in the left occipital temporal lobes, while there was hypoperfusion in the left temporo-parietal area corresponding to the lesion of the old cerebral infarction. A T2-weighted MRI scan showed an abnormal high-intensity area in the left occipital lobe that suggested brain edema. After the admission, the patient was treated with additional anticonvulsant drugs. The tonic seizures in the right hand disappeared and right homonymous hemianopsia and sensory aphasia showed gradual improvement in the next four weeks.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7994994 TI - [A case of adenoid cystic carcinoma manifesting Garcin's syndrome--effectiveness of cerebrospinal fluid ferritin as a tumor marker in malignant CNS involvement]. AB - We reported a 69-year-old man exhibiting Garcin's syndrome caused by adenoid cystic carcinoma of the right submandibular gland. The patient first experienced abnormal sensations in his right cheek, and the cranial nerves on his right side gradually became affected. He was admitted for hoarseness and dysphagia. Physical examination revealed a right submandibular mass, and neurological examination revealed that the first cranial nerve and the fifth to twelfth cranial nerves on the right side were affected. Laboratory examination showed a rise of both serum and cerebrospinal fluid (CSF) ferritin, suggesting an intracranial invasion of the submandibular tumor. But other tumor markers, CSF protein and cell counts, CSF pathologic study and radiological studies for the central nervous system (CNS) were all negative. A submandibular tumor biopsy revealed adenoid cystic carcinoma. The radiation therapy, including the skull base, provided relief of the patient's symptoms, the tumor was reduced and serum and CSF ferritin level decreased. It is possible that CSF ferritin is a sensitive marker for CNS involvement of malignant tumor because of its permeability of the blood brain barrier and the absence of correlation between serum and CSF. PMID- 7994995 TI - [HTLV-1 associated myelopathy (HAM) with severe orthostatic hypotension--a case report]. AB - We present a case of HAM with severe orthostatic hypotension. A 62-year-old woman was admitted to Mito Red Cross Hospital because of orthostatic dizziness and severe gait disturbance. Physical examination revealed a severe orthostatic hypotension (142/90 mmHg (supine) vs. 84/70 mmHg (standing)). Neurological examination revealed weakness and hyperreflexia in the lower extremities, as well as extensor plantar response and spastic gait. In tests of autonomic nervous system, there was no reflex bradycardia in Aschner eye ball pressure test and carotial sinus reflex, no overshoot in Valsalva test, and electrocardiogram revealed a low value in CVR-R. The imprint techniques under 1% pilocarpine subcutaneous administration revealed a marked disturbance of sudomotor function. Blood cell counts, blood chemistry and urinalysis were unremarkable. The serological examination revealed a high titer value of anti-HTLV-1 antibody. Anti HTLV-1 antibody and oligoclonal IgG band were detected in the cerebrospinal fluid. Magnetic resonance imaging (MRI) of the cerebrum demonstrated multiple small high intensity areas in the white matter, but these lesions showed no gadolinium enhancement. Since the test of the autonomic nervous system revealed both sympathetic and parasympathetic disturbance, it is important to investigate the autonomic disturbance including orthostatic hypotension in cases of HAM. PMID- 7994996 TI - [A case of dementia associated with multiple iron deposits in the brain on MRI]. AB - We report a 63-year-old man presenting with dementia and cerebellar ataxia associated with multiple iron deposits in the brain on MRI. Numerous small lesions of low-intensity on both T1- and T2-weighted images were found in the parenchyma and surface of the cerebrum, cerebellum and brain stem. The number and size of lesions were increased on MRI with the method of gradient recalled acquisition in the steady state (GRASS), indicating that they were composed of iron. The similar lesions were not found in any organs on the abdominal GRASS MRI. Any abnormalities were also not found in the cerebral angiography. Meanwhile, the protein and IgG levels and activated CD4-cells were increased in the cerebrospinal fluid, indicating the involvement of chronic inflammation in the iron deposits in this case. PMID- 7994997 TI - [A case of pontine supranuclear facial palsy]. AB - A 56-year-old hypertensive man suddenly developed difficulty in speaking and numbness in the right hand. On admission, he showed moderate right supranuclear facial palsy and right clumsy hand. Three weeks later, he was discharged with only right supranuclear facial palsy. MRI revealed a small infarction in the middle pons. The lesion was situated in the paramedian borderzone between the base and tegmentum. These findings suggest that supranuclear fibers to the facial nucleus descend as a separate bundle from the main pyramidal tract at the mid pontine level. PMID- 7994998 TI - [Crossed cerebello-cerebral diaschisis in olivopontocerebellar atrophy]. AB - We reported a case of crossed cerebello-cerebral diaschisis (CCCD) in olivopontocerebellar atrophy (OPCA). A 49-year-old male was admitted with complaints of titubation, dysarthria and tremor. Examination on admission revealed exaggerated triceps, patella and achilles tendon reflexes on both sides and rigidity in left wrist. Ocular movements were slightly saccadic and speech was scanning or explosive. Finger-nose and heel-knee coordination was poor on both sides (left dominant). Cardiovascular reflex tests showed abnormal findings, suggesting insidious autonomic dysfunction. Brain CT and magnetic resonance imaging (MRI) revealed mild atrophy of the pons and cerebellum. Brain single photon emission computed tomography (SPECT) showed reduced cerebellar N-isopropyl P-(123I) iodoamphetamine (IMP) uptake more prominent on the left than on the right side. A reduction of 123I-IMP uptake was more striking in the right thalamus, basal ganglia and frontal lobe than on the left side. The cerebellar sign which was left dominant and the left extrapyramidal sign were consistent with the side where reduction of 123I-IMP uptake was more prominent. We suggest that CCCD in our case resulted from transneuronal deactivation in the classic anatomical (cerebello-thalamo-cortical) pathway and dopaminergic (cerebello-basal ganglia-cortical) pathway. There is a possibility that CCCD reflects the development of pathological changes in OPCA. PMID- 7995000 TI - Are clinical research grant applications reviewed fairly? PMID- 7994999 TI - [A case of multiple sclerosis with intractable hiccup and acute respiratory arrest]. AB - A 41-year-old woman with multiple sclerosis (MS) manifesting optic neuritis, cerebellar ataxia and myelopathy was admitted for intractable hiccup and aggravation of sensory disturbance in both lower limbs. Magnetic resonance imaging (MRI) revealed a Gd-DTPA enhanced lesion from the level of the medulla oblongata, involving the reticular formation, to that of the vertebral body C2. She became abruptly unable to breath following aggravation of bulbar palsy and tetraplegia and mechanical ventilation was immediately initiated. The next day, voluntary breathing re-appeared but automatic respiratory failure remained unchanged. The respirator was completely removed after one month, and then the breathing was almost normal. In MS patients who develop intractable hiccup as an early symptom, it is suggested that the causative lesion is in the medulla oblongata. In such cases, we must carefully observe the clinical course because expansion of the lesion may induce respiratory failure. PMID- 7995001 TI - Oral triazolam is potentially hazardous to patients receiving systemic antimycotics ketoconazole or itraconazole. AB - BACKGROUND: Triazolam is metabolized by CYP3A4 isozyme. Ketoconazole and itraconazole may seriously interact with some of the substrates of CYP3A4 (e.g., terfenadine); hence their possible interaction with triazolam in humans is important to uncover. METHODS: In this double-blind, randomized, three-phase crossover study, the interaction between ketoconazole, itraconazole, and triazolam was investigated. Nine healthy young volunteers received either 400 mg ketoconazole, 200 mg itraconazole, or matched placebo (control phase) orally once a day for 4 days. On day 4, each ingested a single 0.25 mg dose of triazolam. Plasma concentrations of triazolam and antimycotics were determined, and pharmacodynamic effects were measured up to 17 hours. RESULTS: On average, ketoconazole and itraconazole increased the area under the triazolam concentration-time curve [AUC(0-infinity)] 22-fold and 27-fold (p < 0.001), the peak concentrations threefold (p < 0.001), and the elimination half-life sixfold and sevenfold (p < 0.001), respectively. In seven of the nine subjects, even the maximum concentration of triazolam in plasma was lower without the antimycotics than were the 17-hour concentrations during the ketoconazole and itraconazole phases. All pharmacodynamic effects (e.g., the Digit Symbol Substitution Test) revealed a significant difference between the antimycotic and placebo phases. CONCLUSIONS: Both ketoconazole and itraconazole seriously affect the pharmacokinetics of triazolam and increase the intensity and duration of its effects. Inhibition of CYP3A4 during the absorption and elimination phases of triazolam seems to explain the interaction observed. Because of the potentially hazardous consequences of this interaction, triazolam should be avoided if patients are using ketoconazole or itraconazole. PMID- 7995002 TI - Metabolism of cytochrome P4503A substrates in vivo administered by the same route: lack of correlation between alfentanil clearance and erythromycin breath test. AB - Because there is considerable interindividual variation in both microsomal CYP3A4 activity and CYP3A4 substrate disposition, an established probe of in vivo CYP3A4 activity would represent an important advance in clinical practice. In a previous study, no correlation was found between the 14C-erythromycin breath test and urinary dapsone recovery ratio. However these drugs were administered by different routes, with the orally administered dapsone being exposed to presystemic metabolism by the gut and renal metabolism before the measurement of the urinary ratio. To overcome the variable of route of administration, the aim of this study was to determine whether the elimination of two intravenously administered CYP3A4 substrates (alfentanil and erythromycin) correlate. We compared the metabolism of alfentanil to its CYP3A4-dependent metabolite, noralfentanil, with the erythromycin breath test in 14 young healthy white men. No significant correlation was found between alfentanil metabolism and the erythromycin breath test: alfentanil clearance versus erythromycin breath test, r = 0.45, p = 0.1; partial metabolic clearance to noralfentanil versus erythromycin breath test, r = 0.35, p = 0.23. Because these two CYP3A4 substrates were administered by the same (intravenous) route, we conclude that differences in the route of administration do not explain the lack of correlation between the erythromycin breath test and other probes of CYP3A4 metabolism. PMID- 7995004 TI - Polymorphic arylamine N-acetyltransferase (NAT2) genes in children with insulin dependent diabetes mellitus. AB - Polymorphic liver arylamine N-acetyltransferase (NAT2; EC 2.3.1.5) has been suggested as a susceptibility factor for both insulin-dependent diabetes mellitus (IDDM) and non-insulin-dependent diabetes mellitus. Previous studies reported an overrepresentation of phenotypically fast acetylators among patients with diabetes. With use of an allele-specific nested polymerase reaction, the NAT2 genotypes were determined in 165 clinically well-controlled patients with IDDM and 107 reference children aged from 3 to 18 years. Wild-type and mutated alleles (mutation 1 diagnosed by presence of cytosine at position 341 instead of thymine; M2 by adenine at 590 instead of guanine, M3 by adenine at 857 instead of guanine) were distributed equally in both groups. Genotypes coding fast acetylation (homozygous wild-type and heterozygous wild-type with one of the mutations) were detected in 40.6% and 36.6% of children with IDDM and reference children, respectively (odds ratio, 1.19; 95% confidence limits, 0.70 to 2.04). In 66 children with IDDM and 54 reference children the NAT2 genotype was checked by conventional sulfamethazine (sulfadimidine) phenotyping. There were only five discrepant cases, indicating that NAT2 genotyping enables correct prediction of NAT2 phenotype in about 95% of tested individuals. The fast acetylator genotype could not be established as a host factor for IDDM susceptibility in children. PMID- 7995003 TI - Population pharmacokinetics of midazolam in neonates. AB - OBJECTIVE: To describe the pharmacokinetics of midazolam, a water-soluble benzodiazepine with a short half-life, in critically ill neonates. HYPOTHESIS: Midazolam clearance is reduced in neonates compared with clearance in children, and the doses currently in use, which are derived from pediatric studies, are excessive. PATIENTS AND METHODS: This population study was conducted in 187 neonates requiring intravenous sedation for artificial ventilation. The 531 midazolam concentration measurements obtained were analyzed by use of NONMEM and a two-compartment model with four parameters: clearance (CL), central volume (Vc), peripheral volume (Vp), and intercompartmental clearance (Q). The influence of birth weight (range, 700 to 5200 gm), gestational age (range, 26 to 42 weeks), postnatal age (range, 0 to 10 days), and comedications were investigated. RESULTS: CL and Vc (mean +/- SE) were found to be directly proportional to birth weight (CL = 0.070 +/- 0.013 L/kg/hr; VC = 0.591 +/- 0.065 L/kg). The CL was 1.6 times higher in neonates with a gestational age of more than 39 weeks. It was 0.7 times lower in neonates receiving inotropic support. The postnatal age had no apparent effect on midazolam kinetics. The Vp and Q (mean +/- SE; 0.42 +/- 0.11 L and 0.29 +/- 0.08 L/hr, respectively) were not influenced by any of the covariates studied. There was a large interindividual variability for the pharmacokinetic parameters. CONCLUSION: The mean midazolam doses required for critically ill neonates are lower than those required for older infants. PMID- 7995005 TI - Relationships between pharmacokinetics and nonpulmonary pharmacodynamic effects of theophylline. AB - Concentration-effect relationships between oral theophylline and its nonpulmonary pharmacodynamic effects were examined in a double-blind, randomized, two-way crossover study in which 10 healthy subjects received a single dose of 500 mg ordinary-release theophylline or placebo. Mean plasma theophylline concentrations rose to 16.1 mg.L-1 at 1 hour and 16.8 mg.L-1 at 2 hours. Maximum decreases in plasma potassium (0.33 mmol.L-1) and magnesium (0.039 mmol.L-1) and increases in supine (11.1 mm Hg) and standing (8.0 mm Hg) diastolic blood pressure and plasma total cholesterol (0.59 mmol.L-1) occurred after the achievement of peak plasma theophylline concentrations (negative hysteresis). This delay is consistent with the intracellularly mediated effects of theophylline and with compartmental shifts of electrolytes. Discrepancies between the pharmacokinetic profile and pharmacodynamic effects should be borne in mind when assessing the duration of action of a drug. PMID- 7995006 TI - A pharmacokinetic evaluation of 14C-labeled afovirsen sodium in patients with genital warts. AB - Afovirsen sodium is a 20-mer phosphorothioate oligonucleotide designed to be complementary to the messenger ribonucleic acid sequence for the translation initiation codon of the E2 protein vital to replication of human papillomaviruses types 6 and 11. 14C-Labeled afovirsen was given as a single-dose intradermal injection in each of four warts of five patients to determine the time-dependent changes in concentration of intact afovirsen in genital warts and to determine the systemic absorption and elimination of radiolabeled compound. Intact afovirsen in genital warts was determined by high pressure liquid chromatography analysis of protease K digested extracts. Intact afovirsen was present in wart tissue for at least 72 hours at concentrations several times in excess of the estimated minimal inhibitory concentration of 1 mumol/L. Absorption of radiolabeled afovirsen from the injection site was rapid, with a peak plasma concentration achieved within 1 hour. Clearance of afovirsen was primarily attributable to slow metabolism, with about 30% of the radiolabel eliminated as 14C-CO2 in expired air over a 6-day period after dosing. Radioactivity eliminated in urine represented metabolites of afovirsen. From the clinical pharmacokinetic data presented here and from previously published pharmacokinetic data in rats, the disposition of afovirsen in humans appears to be relatively similar to that in rats. These data suggest that once or twice weekly dosing regimen in the clinic may be appropriate. PMID- 7995007 TI - Discordant effects of enalapril and lisinopril on systemic and renal hemodynamics. AB - OBJECTIVE: To investigate whether there are quantitative differences between the angiotensin converting enzyme (ACE) inhibitors enalapril and lisinopril with respect to their influence on renal versus systemic hemodynamics in humans. METHODS: This was a 12-month, single-blind crossover study in which eight patients with essential hypertension were examined. The main outcome measures were blood pressure and renal hemodynamics during ACE inhibition and/or angiotensin II infusion. RESULTS: The decrease in blood pressure was dose dependent and not significantly different between both drugs. However, with the same blood pressure reduction effective renal plasma flow (ERPF) rose more and filtration fraction (FF) and renovascular resistance (RVR) decreased more after administration of enalapril (20 mg) than after administration of lisinopril (20 mg) (ERPF: 21.9% +/- 2.0% versus 4.4% +/- 2.5%, p = 0.018; FF: -16.7% +/- 2.8% versus -6.6% +/- 2.5%, p = 0.028; RVR: -28.1% +/- 3.1% versus -18.5% +/- 3.7%, p = 0.018). During angiotensin II infusion, with a similar increase in systemic blood pressure, the change in ERPF, FF, and RVR again was more pronounced during enalapril than during lisinopril (ERPF: -14.6% +/- 2.9% versus -7.8% +/- 3.3%, p = 0.018; FF: 18.3% +/- 5.9% versus 12.8% +/- 6.0%, p = 0.028; RVR: 36.7% +/- 8.1% versus 21.9% +/- 4.3%, p = 0.018). CONCLUSIONS: We conclude that in a situation of a comparable systemic blood pressure reduction, enalapril has greater effects on renal hemodynamics than lisinopril. This finding may have implications for the choice of a certain ACE inhibitor in specific disease conditions. PMID- 7995009 TI - Vascular alpha-adrenergic responsiveness is reduced in cirrhosis. AB - Cirrhosis of the liver is associated with altered cardiovascular regulation. Patients with cirrhosis often have decreased total peripheral vascular resistance despite increased sympathetic activity. To determine whether this reduction in effective sympathetic activity may be caused by an alteration in vascular adrenergic responsiveness, we studied nine patients with biopsy-proven cirrhosis and 12 age-matched control subjects. To assess human vascular adrenergic responsiveness, we used dorsal hand vein linear variable differential transformer techniques. Sensitivity for phenylephrine-mediated vasoconstriction was significantly reduced in patients with cirrhosis (median effective dose [ED50] for phenylephrine: cirrhosis, 1514 ng/min; control subjects, 282 ng/min; p = 0.026). In contrast, the effect of isoproterenol did not differ (cirrhosis: 89% +/- 15% of maximal nitroglycerin effect; control subjects 79% +/- 6%; ED50 for isoproterenol: cirrhosis, 38 ng/min; control subjects, 20 ng/min). These studies indicate that vascular alpha-adrenergic responsiveness in patients with cirrhosis is decreased, whereas beta-adrenergic responsiveness remains intact. A selective decrease in vascular alpha-adrenergic responsiveness may contribute to the decreased peripheral vascular resistance in cirrhosis. PMID- 7995010 TI - Comparison of tolerance to intravenous nitroglycerin during nicorandil and intermittent nitroglycerin patch in healthy volunteers. AB - BACKGROUND: Nitrate tolerance is associated with a loss in the hemodynamic response to nitrate during repeated administration. Nicorandil is a new potassium channel agonist with additional nitrate properties. The aim of this study was to determine whether 7-day nicorandil (10 mg orally twice a day) administration attenuates the response to single-dose intravenous nitroglycerin (0.45 mg over 1 minute) in comparison with 7-day intermittent nitroglycerin patch administration (10 mg for 16 of 24 hours). METHODS: This was an open, randomized crossover study performed in 12 healthy volunteers. Blood pressure, heart rate, and their oscillations were measured with use of a noninvasive device. Low-frequency oscillations (66 to 129 mHz) of blood pressure reflect sympathetic activity. Reflex sympathetic activation was measured as after versus before intravenous nitroglycerin difference in low frequency oscillations of blood pressure and heart rate on day 0 and day 7 of each treatment period. Measurements after single dose intravenous nitroglycerin included the maximum decrease in systolic blood pressure and maximum increase in heart rate and sympathetic activation. Tolerance in each group was assessed as the difference in each parameter between day 7 and day 0. RESULTS: Attenuation of the intravenous nitroglycerin-induced decrease in systolic blood pressure (day 7 - day 0) was - 10 +/- 10 mm Hg during use of the nitroglycerin patch and -2 +/- 11 mm Hg during nicorandil (p = 0.03). Similarly, the change in low frequency oscillations of systolic blood pressure was -79 +/- 144 mm Hg-Hz-1/2 during nitroglycerin administration and 60 +/- 139 mm Hg-Hz-1/2 during nicorandil administration (p = 0.04). CONCLUSION: These results indicate that 7-day administration of nicorandil does not attenuate single-dose intravenous nitroglycerin-induced hemodynamic changes or sympathetic activation. In healthy volunteers and at this dosage (10 mg twice a day), cross tolerance between nicorandil and nitroglycerin does not occur. PMID- 7995008 TI - Amiloride-quinidine interaction: adverse outcomes. AB - OBJECTIVES: Previous studies have reported beneficial antiarrhythmic effects when selected drugs were combined. The purpose of this study was to assess whether a favorable interaction would occur with amiloride and quinidine. DESIGN: The antiarrhythmic and electrophysiologic effects of quinidine alone and in combination with amiloride were assessed in 10 patients with inducible sustained ventricular tachycardia. Parallel electrophysiologic studies assessed this drug combination in guinea pig papillary muscle. RESULTS: None of the patients had adverse effects during quinidine monotherapy. However, seven of 10 patients had adverse responses to the combination treatment: three patients had suppression of inducible ventricular tachycardia during quinidine monotherapy but had sustained ventricular tachycardia induced during combination treatment; three other patients had somatic side effects that resulted in discontinuation of the combination therapy but were absent during quinidine monotherapy; and one patient had 12 episodes of sustained ventricular tachycardia during this combination therapy. The patient had no such response during monotherapy. Surface QRS duration was significantly more prolonged during combination therapy than during monotherapy. Parallel electrophysiologic effects assessed this drug combination in guinea pig papillary muscle. The combination of amiloride (1 mumol/L) and quinidine (10 mumol/L) synergistically decreased the maximum rate of rise of phase 0 of the action potential (Vmax) (43 +/- 12 V/sec) compared with quinidine alone (24 +/- 9 V/sec) because of a greater degree of tonic block of Vmax (14% +/ 6%) as compared to quinidine alone (3% +/- 3%) with no significant change in action potential duration. CONCLUSIONS: Amiloride exaggerates the effects of quinidine on QRS duration in patients and on Vmax during in vitro study, which implies that the proarrhythmic effect of the combination of amiloride and quinidine may be associated with synergistic increase in sodium channel blockade. PMID- 7995011 TI - Effects of lisinopril and nitroglycerin on blood pressure early after myocardial infarction: the GISSI-3 pilot study. AB - OBJECTIVES: To evaluate the safety in terms of hypotensive action of nitroglycerin and lisinopril started early after myocardial infarction. PATIENTS AND METHODS: One thousand five hundred twenty-six patients with suspected myocardial infarction were randomized by 174 centers within 24 hours from the onset of symptoms to receive oral lisinopril (5 then 10 mg/day), nitroglycerin (intravenous infusion during the first 24 hours, then 10 mg/day transdermal), or neither. RESULTS: Systolic blood pressure, intensively monitored during the first 72 hours, decreased sharply by 11 mm Hg during the first 2 hours, then more slowly to an average value of 120 mm Hg. Nitroglycerin lowered systolic blood pressure during the first 24 hours by 2.7 mm Hg versus control subjects, and it was similar to control subjects from 24 hours. Lisinopril reduced systolic blood pressure by 4.2 mm Hg over 72 hours compared with control subjects. Persistent hypotension was significantly more frequent in the lisinopril group (21.4%) than in the nitroglycerin group (10.9%) or control group (9.8%), but absolute numbers of deaths in patients with persistent hypotension were almost identical. CONCLUSIONS: Lisinopril and nitroglycerin are both safe and effective in reducing blood pressure in the first day after myocardial infarction. However, the effect is lost thereafter with transdermal nitroglycerin, but persists with lisinopril. PMID- 7995012 TI - The CERT concept: an industry perspective. PMID- 7995013 TI - Introduction: examination of clinical and preclinical pharmacologic data relating to abuse liability of l-deprenyl (selegiline). PMID- 7995014 TI - Pharmacological actions of l-deprenyl (selegiline) and other selective monoamine oxidase B inhibitors. AB - The acetylenic selective monoamine oxidase (MAO) type B suicide inhibitor, l deprenyl (l-selegiline), has proved to be a useful adjuvant to L-dopa therapy and monotherapy of Parkinson's disease. Although not all features of its antiParkinson action are known, studies that used brains obtained at autopsy from patients who took l-deprenyl show that the selective inhibition of MAO-B with a concomitant increase of phenylethylamine and dopamine, but not of serotonin or noradrenaline, in the basal ganglia may be responsible for its mode of action. The increased life expectancy noted in patients with Parkinson's disease who received long-term therapy (9 years in an uncontrolled study) is another unexpected feature of the drug. These exciting data, if confirmed in other long term clinical trials, may herald a neuroprotective approach to the treatment of this degenerative disease. More recent studies indicate that Parkinson's disease may eventually turn out to be a neurotoxic event resulting from oxidative stress induced free radical species in the substantia nigra. Thus selective MAO-B inhibitors could represent a unique class of drugs, having symptomatic actions with possible neuroprotective and neurorescue actions in one. PMID- 7995015 TI - Biochemical actions of l-deprenyl (selegiline). AB - l-Deprenyl is a selective, irreversible monoamine oxidase (MAO) type B inhibitor. Dopamine is a relatively good MAO-B substrate in the human brain. Because Parkinson's disease is characterized by a decrease in dopaminergic neurotransmission in the basal ganglia, the selective inhibition of MAO-B should lead to diminished metabolism of dopamine in the nigrostriatal system and a significant increase in the concentration of the neurotransmitter. MAO-B inhibition explains the clinical efficacy of l-deprenyl in the treatment of Parkinson's disease and the prevention of the conversion of protoxins such as 1 methyl-4-phenyl-1,2,3,6-tetrahydropyridine, which is oxidized by MAO-B and can cause a parkinsonian syndrome, to their active neurotoxin. In addition, l deprenyl appears to exhibit other biochemical actions that are independent of its MAO-B activity. These actions may be the basis of the neuroprotective effects of l-deprenyl and may include the inhibition of oxidative stress, an indirect influence on the polyamine binding site of the N-methyl-d-aspartate receptor and the stimulation of neurotrophic factors. PMID- 7995016 TI - Pharmacokinetic aspects of l-deprenyl (selegiline) and its metabolites. AB - l-Deprenyl (selegiline), an irreversible and selective inhibitor of monoamine oxidase type B (MAO-B), is rapidly absorbed from the gastrointestinal tract and distributed into tissues. The reaction between MAO and selegiline takes place in two steps. The initial reversible reaction is followed by an irreversible reaction in which selegiline is bound covalently to the flavin part of the enzyme. Studies with positron emission tomography have shown retention of selegiline in brain areas with high MAO-B activity, including striatal structures, hippocampus, thalamus, and substantia nigra. Inhibition of MAO-B in vivo takes place rapidly; for example, platelet MAO is inhibited almost totally within the first 60 minutes after a single 10 mg oral dose of the drug. The recovery of MAO after inhibition depends on the organ and species in question. In rat brain the half-life of recovery in the brain is approximately 8 to 12 days; in rat liver it is shorter, 1 to 3 days. Selegiline is metabolized into l-(-) desmethylselegiline, l-(-)-methamphetamine, and l-(-)-amphetamine mainly in the liver through the microsomal P-450 system. The stereoselectivity of the metabolites is maintained; no racemic transformation takes place. All three main metabolites are found in human serum, cerebrospinal fluid, and urine, and l-(-) methamphetamine accounts for most of the metabolite pool. The metabolites are excreted mainly via urine l-(-)-Desmethylselegiline has been shown to be an irreversible inhibitor of MAO-B in the rat and in humans. PMID- 7995017 TI - Therapy with l-deprenyl (selegiline) and relation to abuse liability. AB - This article briefly reviews the clinical aspects and rationale for therapy with l-deprenyl for several neuropsychiatric conditions, including major depression, Alzheimer's disease, and Parkinson's disease. The rationale for the use of l deprenyl in these conditions is discussed, and evidence for efficacy is reviewed. Lastly, there is a review of the lack of evidence for l-deprenyl's abuse potential and its use as putative nonspecific cognitive enhancer, a so-called "smart drug." Although l-deprenyl itself appears to have no abuse potential, it is theoretically possible that it might potentiate the actions and frequency of dosage and use of various drugs of abuse or dependence. This is as yet an underresearched area, and more work is required. PMID- 7995018 TI - Evaluation of physical dependence liability of l-deprenyl (selegiline) in animals. AB - l-Deprenyl is a useful drug that has been successful in the clinical treatment of parkinsonism. However, l-deprenyl is a phenylalkylamine derivative that undergoes metabolic transformation to l-methamphetamine and l-amphetamine. Therefore, the question arises whether l-deprenyl possesses amphetamine-like abuse liability. This article reviews a series of different preclinical studies in rats that used experimental procedures to provide preclinical information predictive of human abuse liability. In one series we investigated whether repeated administration of l-deprenyl to rats resulted in observable signs of physical dependence. In a second series of studies, the effects of l-deprenyl on the cortical electrical activity of freely moving rats were investigated. Finally, the influence of l deprenyl on behavior of the animals was studied. In all studies, different stereospecific configurations of amphetamine and deprenyl were compared. During and after 6 weeks of oral administration of l-deprenyl, no signs of physical dependence were observed in rats after withdrawal of the drug. In contrast, with d-deprenyl, d-amphetamine, and racemic d,l-amphetamine, signs indicative of physical dependence were observed after withdrawal of the drug. For example, the body weight of the rats was increased. In addition, changes in electroencephalograms and behavior of rats induced by l-deprenyl and l amphetamine were different from those produced by the d-enantiomers. Thus preclinical results confirm the clinical experience that therapeutically relevant doses of l-deprenyl are without physical dependence liability. PMID- 7995019 TI - Amphetamine-like effect of l-deprenyl (selegiline) in drug discrimination studies. AB - l-Deprenyl has dose-dependent amphetamine- and methamphetamine-like discriminative stimulus properties in rats and monkeys. However, these actions occur only at doses that are well above the clinically relevant dose range for l deprenyl and are likely to reflect its metabolic conversion to amphetamine products. In view of its weak potency for producing amphetamine-like effects and their slow onset, it may not be surprising that l-deprenyl does not appear to have amphetamine-like abuse potential and has been used therapeutically in the treatment of Parkinson syndrome for more than 20 years with no reported instances of abuse. PMID- 7995020 TI - Intravenous self-administration studies with l-deprenyl (selegiline) in monkeys. AB - l-Deprenyl and its stereoisomer d-deprenyl did not maintain intravenous self administration behavior in rhesus monkeys. In contrast, l-methamphetamine, the major metabolite of l-deprenyl, as well as the baseline drug, cocaine, maintained high rates of intravenous self-administration behavior. Treatment with l-deprenyl doses up to 1.0 mg/kg before self-administration sessions failed to alter self administration of either cocaine or l-methamphetamine. Thus l-deprenyl did not appear to have cocaine- or methamphetamine-like reinforcing properties in monkeys and was ineffective in altering established patterns of psychomotor-stimulant self-administration behavior. These results support clinical findings that despite long-term use of l-deprenyl for the treatment of Parkinson's disease by large numbers of patients, no instances of abuse have been documented. l-Deprenyl has recently been suggested as a potential medication for the treatment of various types of drug abuse, including cocaine abuse, but its failure to produce selective effects in decreasing cocaine or methamphetamine self-administration behavior in the present experiments makes such an application seem unlikely. PMID- 7995021 TI - What is it that l-deprenyl (selegiline) might do? AB - There have been many claims that l-deprenyl may have distinct properties in slowing and perhaps even in reversing the progression of Parkinson's disease and other neurodegenerative conditions. This article will consider the paucity of evidence that such is the case in humans and the more detailed results from studies with experimental animals indicating that deprenyl may indeed express such a property. The conflicting data on its mechanism of action are considered and the concept that it may function to enhance neuronal fitness is advanced as an alternative to the neuroprotection and neurorescue hypotheses. Possible lines of experimental development that would help resolve some of the many unanswered questions regarding l-deprenyl function are outlined. PMID- 7995022 TI - Head pain. Diagnosis and management. PMID- 7995023 TI - Personality disorder traits in generalized anxiety and panic disorder patients. AB - Eight-four panic disorder (PD) and 29 generalized anxiety disorder (GAD) patients were compared with respect to abnormal personality traits assessed by a structured interview (Structured Interview for DSM-III Personality [SIDP]) and a self-report inventory (Personality Diagnostic Questionnaire [PDQ]). An earlier study using many of the same patients by Noyes et al. found PD patients to have more extensive axis I psychopathology than GAD patients. However, in this study it was the GAD patients who appeared to have greater axis II pathology. In particular, when using a subset of patients who had been matched for age and gender, the GAD patients reported more antisocial traits. This finding is particularly interesting, since the matched samples consisted primarily of women in their forties and fifties. PMID- 7995024 TI - Personality disorders and associated features in cocaine-dependent inpatients. AB - Previous research has shown a high prevalence of comorbid personality disorders among individuals seeking treatment for cocaine dependence. We studied axis II disorders (using the Structured Clinical Interview for DSM-III-R Personality Disorders [SCID-II]) in 50 patients admitted for inpatient rehabilitation. All patients met lifetime criteria for cocaine dependence and reported cocaine use during the month before admission. Seventy percent of patients met criteria for at least one axis II diagnosis; the mean number of axis II diagnoses among these patients was 2.54 (range, one to six). The most common axis II diagnosis was borderline (34% of all patients), followed by antisocial and narcissistic (each 28%), avoidant and paranoid (each 22%), obsessive-compulsive (16%), and dependent (10%). To evaluate the relationship between comorbid personality pathology, substance abuse, and other psychiatric symptomatology, patients were divided into two groups based on whether they received an axis II disorder diagnosis. The groups did not differ on substance abuse variables. However, there were significant group differences on a measure of psychosis proneness and in the number of comorbid depressive and anxiety disorder diagnoses. These results are consistent with other studies of personality disorders in substance abuse patients, and suggest that it may be clinically useful to characterize cocaine dependent patients with respect to comorbid axis II disorders. PMID- 7995025 TI - Best-estimate versus structured interview-based diagnosis in first-admission psychosis. AB - In a sample of first-admission psychotic patients, best-estimate diagnoses made by psychiatrists at entry to the study (N = 310) and 6 months later (N = 228) were compared with Structured Clinical Interview for DSM-III-R (SCID) algorithm diagnoses. Sensitivity, specificity, and agreement (kappa) at entry and at 6 month follow-up evaluation were satisfactory for schizophrenia (sensitivity, .89 and .98; specificity, .96 both times; kappa, .86 and .92) and bipolar disorder with psychosis (sensitivity, 1.00 and .94; specificity, .96 both times; kappa, .89 and .88), moderate for major depression with psychosis (sensitivity, .90 and .81; specificity, .94 and .95; kappa, .75 and .72), but mixed for the organic psychoses (sensitivity, .50 and .23; specificity, 1.00 both times; kappa, .66 and .36). Reasons for disagreement included the role of drugs and other organic factors in the etiology of the disorder, and clinical judgment versus the rules of the structured interview. We conclude that the SCID, when administered by closely supervised experienced nonpsychiatrist clinicians and incorporating information from other sources, can produce a reliable diagnosis of schizophrenia and bipolar disorder. However, the best-estimate procedure seems mandatory in studies investigating a broad range of psychoses, where the use of drugs is not an exclusion criterion. PMID- 7995026 TI - The symptom structure of panic attacks. AB - Panic attack symptomatology was investigated in 212 panic disorder patients (60 men, 152 women) using the Panic Attack Questionnaire, Feelings of helplessness and thoughts of escape had the highest mean severity ratings, but are not currently listed in the DSM-III-R. The DSM-III-R symptoms labeled choking or smothering sensations, paresthesias, nausea, and chest pain had low severity ratings. Evidence was obtained for a three-factor model of panic symptomatology consisting of dizziness-related symptoms, cardiorespiratory distress, and cognitive factors. These results provide only limited support for the current DSM III-R symptom structure, and support the notion that panic disorder is a heterogeneous condition. PMID- 7995027 TI - Characterizing organic mood syndrome, manic type. AB - The purpose of this study is to provide the first empirically based description of the clinical features of organic mood syndrome, manic type (OMS-M). During a recent 5-year period, 14,889 new patients presented for initial evaluation and care at our institute. Of these patients, a total of 12 cases of OMS-M were diagnosed. Evaluations were conducted using the Initial Evaluation Form, which was developed to be compatible with the DSM-III. The symptom profile of OMS-M was compared with that of "functional" manics (bipolar disorder, manic type [BD-M]). A variety of associated clinical factors were also assessed. The OMS-M patient demonstrated somewhat less severe acute symptomatology but more longstanding functional impairment than in BD-M. OMS-M patients also displayed a lower age at onset of illness and a higher level of perinatal problems and developmental delays compared with BD-M patients. The OMS-M group displayed a low family burden of mania. The most striking distinguishing feature of OMS-M was the prevalence of neurological disorders, with a surprisingly high prevalence of seizure disorders. Seizure disorders were more prevalent in OMS-M than in other organic brain syndromes (OBS). PMID- 7995029 TI - Anhedonia and blunted affect in major depressive disorder. AB - The relation between anhedonia and affective flattening was studied in 61 normal subjects and 61 major depressives. Affective flattening and anhedonia were defined by the following self-rating scales: Fawcett-Clark Pleasure Capacity Scale (FCPCS), Hardy Displeasure Capacity Scale (HDCS), FCPCS-PP (subscale of physical pleasure), and HDCS-PD (subscale of physical displeasure). The depressives are more sensitive to displeasure and more anhedonic than controls. Concerning physical stimulations (FCPCS-PP and HDCS-PD) in the depressed group, anhedonia and affective flattening are not linked, suggesting that physical anhedonia is not secondary to low emotional reactivity (affective flattening) and constitutes an independent dimension. PMID- 7995028 TI - Changes in diagnosis in a 9-year national longitudinal sample. AB - Studied are changes in diagnosis in a random sample of 10% of all first admissions to psychiatric hospitals and psychiatric wards of general hospitals in Israel from 1983 to 1990 with follow-up evaluation to 1991. This included 4,570 hospitalizations of 2,220 patients. Data were extracted from the National Psychiatric Case Registry of the Ministry of Health. Almost 59% of the sample had one admission, 18% had two, 9% had three, and 14% had four or more. From the first admission to the last discharge (a mean of 2.15 years), 59.2% of the patients' diagnoses did not change. In 89.46% of the cases in which the diagnosis changed, the changes took place during the first admission. Diagnostic change differed between diagnostic groups. In descending order of stability in diagnosis from the first admission to the last discharge were neurotic and personality disorder (73.6%), mental retardation (73.5%), schizophrenia (73.0%), organic conditions (70.6%), affective disorders (66.2%), substance abuse (65.6%), childhood disorders (60%), paranoid disorder (43.6%), other nonorganic psychosis (30.3%), and V-codes (25.0%). The average level of diagnostic agreement between the first admission and the last discharge was a kappa of .52. The average length of stay for patients whose diagnosis became more severe was considerably longer than for patients whose diagnosis became less severe or did not change in level of severity. Older age was related to less change in diagnosis. For patients aged less than 18 years, diagnosis changed in 46.7% of the cases, for patients aged 19 to 44, 31.2%, and for patients older than 45, 27.8%. PMID- 7995030 TI - Aggression and its correlates in Vietnam veterans with and without chronic posttraumatic stress disorder. AB - This study measured self-reported aggression, hostility, and anger in Vietnam combat veterans with (n = 27) and without (n = 15) posttraumatic stress disorder (PTSD). On the Buss-Durkee Hostility Inventory, Past Feelings and Acts of Violence Scale, Episodic Dyscontrol Scale, and State-Trait Anger Expression Inventory (STAXI), PTSD subjects scored significantly higher than non-PTSD subjects, whose scores fell in the range reported for normative, noncombat populations. The PTSD versus non-PTSD group differences were not explained by combat exposure, which did not correlate significantly with the psychometric aggression measures. These findings suggest that increased aggression in war veterans is more appropriately regarded as a property of PTSD, rather than a direct consequence of military combat. The association between compromised neurologic and neuropsychologic status and the psychometric measures was modest and explained little of the group differences. PMID- 7995031 TI - Comparison of American and Japanese outpatients with borderline personality disorder. AB - The borderline psychopathology of 33 American and 19 Japanese female outpatients who met the Revised Diagnostic Interview for Borderlines (DIB-R) criteria for borderline personality disorder (BPD) was compared. There were significant differences between the samples in the DIB-R total score, as well as in the affect/cognition section and scaled section scores. However, only one of the 22 summary statements (SS) of the DIB-R distinguished American borderlines from Japanese borderlines. Most of the differences seemed to reflect differences in inclusion criteria. It is concluded that there are borderline patients in Japan whose psychopathology is basically identical to that of American borderline patients. PMID- 7995032 TI - Psychopathology correlates of binge eating and binge eating disorder. AB - The present study examined the psychopathology associated with binge eating disorder (BED), a new diagnostic category proposed for DSM-IV to classify patients with significant binge eating problems in the absence of purging. Self report measures of psychopathology (e.g., depression, anxiety) and body image disturbance were administered to 72 women who prospectively (1) met criteria for BED (DSM-IV criteria), (2) reported frequent bingeing but did not meet BED criteria, and (3) denied problems with eating. Subjects satisfying BED criteria reported higher levels of psychopathology than normals on all measures and subclinical binge eaters scored between these two groups, but they were closer to subjects without eating problems. The pattern of results was essentially unchanged when corrected for weight. BED subjects and subclinical binge eaters were less satisfied with their bodies than were normal controls. These findings suggest that BED is not only characterized by frequent bingeing, but more importantly is associated with elevated psychopathology. Overall, these results lend support to the diagnostic criteria proposed for BED. PMID- 7995035 TI - The current treatment of lumbar disc herniation. PMID- 7995033 TI - Immigrant status and gender effects on psychopathology and self-concept in adolescents: a test of the migration-morbidity hypothesis. AB - Evidence for a relationship between immigrant status and psychological morbidity (which we shall refer to as the "migration-morbidity" hypothesis) in adolescents is variable and inconclusive. The present study tests this hypothesis and also explores gender differences in self-reported psychopathology and self-concept measures. Native-born Australians, Australian-born adolescent children of immigrants, and immigrant and refugee adolescents are compared on a number of relevant measures. The results do not support the migration-morbidity hypothesis. However, Vietnamese refugee adolescents had poorer self-concept than the other groups. PMID- 7995034 TI - The qualitative difference of visions and visual hallucinations: a comparison of a general-population and clinical sample. AB - Our objective was to analyze the frequency and quality of visions in a general population sample compared with those experienced among schizophrenics. A sample group from the general population (n = 862) was compared with a group of schizophrenic patients (n = 19). Significant and qualitative differences were found in visions experienced by schizophrenic patients compared with subjects in the population sample. Women were more likely to experience visions of relatives than were men. The general population most commonly experienced visions of people, whereas schizophrenics were more likely to experience other phenomena. A qualitative difference thus exists in the type of visions experienced by schizophrenics compared with visions experienced by subjects from the general public. PMID- 7995037 TI - Occupational medicine and the medical center. PMID- 7995036 TI - Intracranial aneurysms: size, risk of rupture, and prophylactic surgical treatment. AB - Intracranial saccular aneurysms frequently cause devastating neurologic injury when they rupture. With recent improvements in diagnostic imaging, however, an increasing number of aneurysms are now diagnosed in the unruptured state. Controversy exists regarding the appropriate management of these lesions. We have retrospectively examined a group of 86 patients from Connecticut with 104 intracranial aneurysms to determine whether small (less than 10 mm in greatest diameter) aneurysms have potential for rupture, and whether there is a role for prophylactic surgical therapy for these unruptured aneurysms. The majority of ruptured and unruptured aneurysms in the series measured less than 10 mm in greatest diameter. Out of a total of 82 patients who underwent surgical therapy, 44 had surgery for unruptured aneurysms. The major surgical morbidity in this group was 2%. We conclude that surgical therapy for small unruptured intracranial aneurysms may be beneficial since these lesions likely have substantial potential for rupture and because surgical treatment carries an acceptable risk. PMID- 7995038 TI - Safe harbors and stark realities. PMID- 7995039 TI - Optimal calcium intake. National Institutes of Health. PMID- 7995040 TI - Malignant melanoma. PMID- 7995041 TI - Multimodality therapy in gynecologic oncology. PMID- 7995042 TI - ATP-cell viability assay methodology in both fresh gynecologic tumors and cell lines. PMID- 7995043 TI - Overview of currently used chemosensitivity test systems in gynecologic malignancies and breast cancer. PMID- 7995044 TI - In vivo/in vitro correlation of xenografts in nude mice and the ATP-cell viability assay. PMID- 7995045 TI - Review of data on gynecologic cancer cell lines: potential applications of ATP cell viability assays. PMID- 7995046 TI - Evaluation of new drugs and combinations in gynecologic tumors and cancer cell lines with the ATP-cell viability assay. PMID- 7995047 TI - Application of the ATP-cell viability assay for assessment of in vitro radiation treatment response in gynecologic cancer cell lines. PMID- 7995048 TI - Application of the ATP-cell viability assay for assessment of biologic response modifiers in gynecologic cancer. PMID- 7995050 TI - Clonogenic assays for gynecologic malignancies. Methodology and results. EORTC Preclinical Therapeutic Models Groups (PTMG). PMID- 7995049 TI - Current status and future directions of chemosensitivity testing. PMID- 7995051 TI - Short-term assay (radiolabeled DNA-precursor uptake method) in gynecologic malignancies. Methodology and results. PMID- 7995052 TI - Use of the extreme drug resistance assay to evaluate mechanisms of resistance in ovarian cancer: taxol resistance and MDR-1 expression. PMID- 7995053 TI - The fluorescent cytoprint assay in gynecological malignancies and breast cancer. Methodology and results. PMID- 7995054 TI - The identification of drug resistance in ovarian cancer and breast cancer: application of the MTT assay. PMID- 7995055 TI - In vivo chemosensitivity test models for gynecologic malignancies. Methodology and results. PMID- 7995056 TI - Clinical correlations for cell culture assays based on the concept of total tumor cell kill. PMID- 7995057 TI - Assessment of synergistic and antagonistic effects of chemotherapeutic agents in vitro. PMID- 7995058 TI - Demonstration of feasibility of application of a portable keratometer to cadaveric donor corneas. AB - An automated portable keratometer was used to measure corneal curvatures of cadaveric donor corneas. Globe contours were maintained despite unrecordable intraocular pressures, and reproducible keratometric values were consistently obtainable. Evaluation of nondonor eyes, at varying intraocular pressures (IOPs) ranging from 0 to 66 mm Hg (Schiotz), yielded keratometric readings that were not significantly different at different IOPs. Early correlation of keratometric values in five grafted eyes showed a trend of +/- 0.5 D from measured cadaveric donor keratometry values when compared with that of the donor sutured into the recipient bed. The study suggests the feasibility of incorporating cadaveric donor keratometry readings in the prediction of final donor keratometric values in the recipient bed, thus allowing more accurate selection of intraocular lens powers for triple procedures and the avoidance of transplanting corneas with unusual or abnormal corneal curvatures. PMID- 7995059 TI - Corticosteroids in corneal graft rejection: double versus single pulse therapy. AB - In a previous study, we reported that a single intravenous pulse of 500 mg of methylprednisolone is more effective than oral prednisone in reversing rejection in patients who present early with severe endothelial rejection. In addition, the grafts that survived were less likely to undergo a further rejection episode. This study investigates whether a second pulse given at 24 h (n = 31) or at 48 h (n = 29) has any advantage over a single pulse (n = 30). All three treatment regimens were equally effective in reversing rejection (74.2%, 79.3%, and 83.3%, respectively), and there was no statistical difference in graft survival. An additional pulse therefore appears to offer no advantage over single pulse therapy. In high-risk grafts, current therapy has been reported to be less effective in reversing graft rejection. This study showed no significant difference between high- and low-risk grafts, indicating that pulse therapy may have a particular role in these difficult cases. PMID- 7995060 TI - Human allograft limbal transplantation for corneal surface reconstruction. AB - Limbal allograft transplantation was performed consecutively in 16 eyes with thermal or chemical burns (n = 5), Terrien's degeneration (n = 2), congenital sclerocornea (n = 1), Stevens-Johnson syndrome (n = 1), and chronic keratoconjunctivitis (n = 7), by transplanting randomly selected cadaver limbocorneal grafts to the recipient eye that had received superficial lamellar keratectomy to remove fibrovascular pannus. Oral cyclosporine A was administered immediately for 2.9 +/- 1.3 months. During 18.5 +/- 5.4 months of follow-up, the results showed improved visual acuity in 13 eyes (81.3%) and rapid (within 1 week) surface healing in 10 eyes (62.5%). Donor limbal tissue developed engorged and tortuous blood vessels in 12 eyes within 1-2 months, but these regressed within 3 months after surgery. No acute graft failure or allograft rejection could be identified. Twelve eyes (75%) showed total regression of vascularization and four eyes had decreased vascularization. These preliminary results indicate that limbal allograft transplantation may be able to reconstruct a corneal surface that has undergone bilateral diffuse destruction, including the loss of limbal epithelial stem cells. PMID- 7995061 TI - Corneal tattooing to reduce glare in cases of traumatic iris loss. AB - The traumatic loss of iris is often associated with symptoms of glare, which can be debilitating. This symptom may be benefitted by wearing a contact lens with a clear, central optical zone and opacification of the remainder. The patient who is contact lens-intolerant may be helped by tattooing of all of the cornea except the central visual axis. Four patients who had traumatic iris loss and who were treated by this technique reported reduced glare as well as improvement in the cosmetic appearance of the eye. Although corneal tattooing is an ancient procedure, it continues to be of benefit for selected patients. PMID- 7995062 TI - Photodynamic biologic tissue glue. AB - We studied both heat- and light-activated tissue glues, and while a heat activated mixture such as albumin and fluorescein isothiocyanate was effective, we believed that a light-activated substance would have less of an effect on adjacent tissue. Our glue uses a photosensitive singlet oxygen generator to cross link a protein solder with corneal stromal collagen. The mixture consists of 18% fibrinogen and 2.6 mg/ml of riboflavin-5-phosphate activated with a blue-green (488-514 nm) Argon laser. We tested our glue by soldering 5-mm penetrating central corneal incisions made in human cadaver eyes. The strength of the closure was measured by cannulating the vitreous cavity with an 18-gauge needle connected to a saline reservoir. The pressure in the reservoir was elevated by connecting it to a sphygmomanometer. Immediately following tissue closure, the intraocular pressure was increased until the wound burst. We soldered and measured 10 eyes and found a mean bursting pressure of 154 mm Hg, with a range of 80-260 mm Hg. Our laser-activated tissue glue is an effective adhesive for corneal tissue, and we now plan to carry out toxicity studies in living animals. PMID- 7995063 TI - Single dosage of mitomycin C for prevention of recurrent pterygium: preliminary report. AB - We studied the recurrence rate of pterygium after administration of a single dosage of topical mitomycin C at the completion of pterygium surgery. Forty patients who had advanced or recurrent pterygium underwent excision of pterygium, leaving the sclera bare. Patients were randomized in a masked fashion into two groups of 20 patients each. Group 1 received a single dosage of topical 0.02% mitomycin C for 5 min at the completion of the surgery whereas group 2 underwent the same procedure but received NaCl 0.9% instead of mitomycin C. Patients were followed from 6 to 15 months in a masked manner. The pterygium recurred in one patients (5%) in group 1, whereas in group 2 the recurrence rate was 45% (p = 0.0035). Formation of dellen and a delay of epithelialization for 5 weeks were found in one patient in group 2. No complications were observed in patients in group 1. This study indicates the possible advantage of administration of a single dosage of 0.02% mitomycin C for postoperative prevention of recurrence of pterygium. PMID- 7995064 TI - A double-blind, randomized study of Healon GV compared with Healon in penetrating keratoplasty. AB - A double-blind, parallel, randomized study was conducted to compare the efficacy of Healon GV versus Healon in penetrating keratoplasty (PK). Its objective was to investigate whether Healon GV maintains space in the open anterior chamber better than Healon does during removal of the corneal button. Excluding those patients with an anterior chamber lens implant or a known history of glaucoma, 35 patients scheduled for PK entered the study. After penetration of the cornea with the trephine, a specific amount (0.2 ml) of Healon GV or Healon was injected into the anterior chamber. The corneal button was removed and the distance (mm) between iris and cornea (epithelial side) was measured with a digital slide gauge mounted between the permanent and mobile stand of the microscope. A significant difference between the two groups was shown in the measurements of the distance between the iris and the outer side of the cornea. The mean distance for Healon GV was 1.5 +/- 0.6 mm and for Healon it was 1.1 +/- 0.4 mm (p = 0.038). The removal of the corneal button was significantly facilitated when Healon GV was used (p = 0.021). In conclusion, Healon GV was found to be superior in the ability to maintain space in the open anterior chamber. PMID- 7995065 TI - Penetrating keratoplasty and intraocular lens exchange: open-loop anterior chamber lenses versus sutured posterior chamber lenses. AB - Penetrating keratoplasty with intraocular lens (IOL) exchange is generally recommended for eyes with pseudophakic bullous keratopathy, especially when the keratopathy is associated with uveitis, chronic cystoid macular edema, or a uveitis-glaucoma-hyphema syndrome. Review of the literature has shown basically equivalent long-term results of penetrating keratoplasty and IOL exchange using both Kelman-style, flexible, open-loop anterior chamber lenses and acapsular fixation of sutured posterior chamber lenses. The use of suture-fixated posterior chamber IOLs appears warranted in centers where the surgeon has extensive experience with this specific technique and in cases with special indications, for example, in eyes with extensive angle abnormalities. However, because this technique is more difficult to perform, and in the absence of such preexisting contraindications, for most practices we do not hesitate to recommend the use of a Kelman-style anterior chamber lens during routine cases of penetrating keratoplasty and IOL exchange. PMID- 7995066 TI - Silicone rubber contact lenses for the compromised cornea. AB - Silicone rubber contact lenses (SRCLs) are infrequently used because of the risk of developing unpredictable lens tightening, their poor availability, and their expense. However, their high oxygen transmissibility and nonabsorption of water make them valuable as therapeutic lenses. SRCLs are routinely used in our management of severely dry eyes, decompensated or vascularised corneas, and conditions where the corneal shape is flat or irregular. The records of 48 consecutive patients fitted with SRCLs between January 1989 and June 1990 were studied. The clinical history, indications, complications, success, and duration of SRCL wear were analysed. Therapeutic goals, which included epithelial healing, sealing of corneal perforations, and improved comfort and vision, were achieved in 53 of 62 eyes. The best corrected acuity was attained using SRCLs in 58 of 62 eyes. Failure of lens wear was due to lens tightening (four eyes), spoilation (two), discomfort, fornix shortening, handling problems, and decentration (one each). Infective keratitis complicated one case, but SRCL wear was resumed after successful treatment. With adequate follow-up, SRCLs have a low complication rate and are well tolerated even in severely compromised eyes, for which conventional lenses may be contraindicated. Their continued use as therapeutic lenses is advocated in carefully selected cases. PMID- 7995067 TI - Effects of rigid lens extended wear on lactate dehydrogenase activity and isozymes in rabbit tears. AB - Effects of and recovery from continuous wear of four rigid gas permeable (RGP) contact lenses was assessed by noninvasive measurement of lactate dehydrogenase (LDH) activity and isozyme pattern in rabbit tears. Oxygen transmissibility (Dk/L) of lenses used was 27, 44, 84, and 97 x 10(-9) (cm/s)(ml O2/ml mm Hg); lens thickness (0.15 mm) and diameter (14.0 mm) were standardized. Lenses were worn continuously for 90 days; recovery was assessed 30 days after cessation of lens wear. LDH activity was measured by UV rate assay; isozyme subtypes were determined by agarose gel electrophoresis. Light and scanning electron microscopy (LM, SEM) were used with the determination of total protein as additional measures of lens effects. LDH levels were inversely correlated with lens Dk/L values; low Dk/L values increased the anaerobic (LDH4,5)/aerobic (LDH1,2,3) subtypen ratio indicating in vivo metabolic shift. SEM observations were consistent with these results. There was no significant difference in the total cell content of tears or total tear protein levels between control and RGP test wear groups. Measurement of tear LDH activity and isozyme ratios appears to provide a sensitive, noninvasive assessment of the effects of RGP lens-induced hypoxia over time on the corneal surface. A level of Dk/L of > or = 84 appears best for maintaining corneal physiology during extended wear. Recovery from chronic lens-induced hypoxia is characterized by a return to normal tear LDH levels and isozyme subtypes. PMID- 7995068 TI - Activity of ganciclovir against human adenovirus type-5 infection in cell culture and cotton rat eyes. AB - The most common causes of acute viral infections of the eye for which there are no effective antiviral drugs are the adenoviruses. Until recently, pathogenesis studies and antiviral drug testing for adenovirus-induced ocular disease were not practical because no animal model was available. However, new animal models for human adenovirus-induced ocular and respiratory infections have now made such studies possible. We assessed the in vitro and in vivo activity of ganciclovir against a genetically defined adenovirus (Ad5 wt 300) known to cause severe ocular disease. The 50% inhibitory dose (ID50) values were determined by plaque reduction assays in human cells. The ID50 values of 47 and 604 microM were determined for ganciclovir and acyclovir, respectively, against Ad5, and 26 and 152 microM, respectively against Ad8. Cotton rats were inoculated bilaterally with 10(5) plaque-forming units per eye and treated topically with ganciclovir (3%, 1%, or 0.3%) or placebo for 21 days. All inoculated eyes were culture positive on days 1-3 with increased infectivity titers, regardless of treatment. However, the incidence, duration, and titer of virus shed in eyes treated with 3% ganciclovir was reduced, and the antiadenovirus enzyme-linked immunosorbent assay titers in serum were lower in these animals. Although these differences were not statistically significant, the observed trend suggested that the highest ganciclovir dose had a suppressive effect on some disease parameters. PMID- 7995069 TI - Interleukin-2 receptor--targeted therapy by monoclonal antibodies in the rat corneal graft. AB - A possible selective therapeutic approach to corneal graft rejection will aim at IL-2 receptor-bearing antigen-activated T-lymphocytes with monoclonal anti IL-2R antibodies. In a rat penetrating keratoplasty model (Lewis x Lewis-BN) comparing to controls (median, 8 days), a significant delay of the allograft reaction was achieved by applying a therapeutic dose (15 mg/kg bw) of cyclosporin A (median, 18 days; p < 0.01), an intraperitoneal (1.0 mg/kg bw) (median, 13.5 days; p < 0.05) or a subconjunctival injection of IL-2R mab (0.5 mg/kg bw ART-18) (median, 16 days; p < 0.01) with low-dose Cyclosporin A (1.5 mg/kg bw). In pharmacokinetic experiments, the corneal radioactivity 24 h after intraperitoneal injection of 125I-labeled ART-18 was < 1% (p < 0.01) of the values obtained by subconjunctival injection, whereas the serum radioactivity values (p > 0.05) were in the same range. The above results suggest that the onset of an allograft reaction in perforating keratoplasty seems to depend on the locally achievable antibody concentration and can be delayed with a high level of IL-2 R mab present in the immediate surrounding of the foreign antigen-expressing cells. PMID- 7995070 TI - Suppression of corneal allograft rejection by systemic cyclosporine-A in heavily vascularized rabbit corneas following alkali burns. AB - Immunologic rejection is the main cause of corneal graft failure, especially in vascularized corneal beds. The purpose of this study was to investigate the effect of systemic Cyclosporine-A (CsA) on the survival of corneal allografts in heavily vascularized rabbit corneal beds, following alkali burn. Heavy corneal vascularization was induced in one eye of 20 rabbits by alkali burn. Forty-five days later, penetrating keratoplasty was performed in all the heavily vascularized corneas. Twenty-five mg/kg/day of CsA was intramuscularly administered to 10 rabbits for 30 days. The other 10 rabbits were treated with the solvent without CsA and were used as a matched control group. The results show a significant difference in corneal allograft survival between the two groups. All corneal grafts in the untreated group were intensely rejected and vascularized within 3 weeks. Nine of the 10 corneal transplants, in the CsA treated group, remained transparent without signs of immunologic rejection for > 180 days. In one corneal transplant, minor signs of rejection occurred. We suggest that CsA, when given systemically, is a potent drug in the prevention of immunologic rejection in high-risk corneal transplantations, such as allografts, in heavily vascularized corneas following alkali burn. PMID- 7995071 TI - Bilateral penetrating keratoplasty for sclerocornea in an infant with monosomy 21. Case report and review of the literature. AB - An 8-month-old caucasian girl with monosomy 21 and sclerocornea underwent bilateral penetrating keratoplasties. Both light and electron microscopic studies were performed on the corneal buttons. Light microscopy revealed variable and abnormal corneal thickness with the peripheral cornea being thinner than the center, lack of Bowman's layer, irregular stromal lamellae, stromal vascularization, markedly underdeveloped or absent Descemet's membrane, and marked attenuation of the endothelium. Electron microscopy demonstrated basal epithelial cells with a thin epithelial basement membrane residing directly on stromal lamellae without intervening Bowman's layer. Stromal collagen fibrils were irregular in size measuring 38-69 nm in diameter. We believe this to be the first report of corneal transplantation and the second reported case of sclerocornea in a patient with monosomy 21. PMID- 7995072 TI - Successful treatment of Acanthamoeba keratitis by hexamidine. AB - Acanthamoeba keratitis remains very difficult to treat because of the lack of antiamoebic agents completely effective against cysts. Currently, the recommended treatment includes the use of topical neomycin sulfate, various imidazoles, and propamidine isethionate (Brolene) 0.1% eye drops, a compound of the diamidine family. In the present article, we describe the successful management of two patients with an Acanthamoeba keratitis, treated with hexamidine diisethionate (Desomedine) 0.1% eye drops, another diamidine derivative, which was found amoebicidal in vitro on the isolated Acanthamoeba strains. This is to our knowledge the first report on the amoebicidal effectiveness of hexamidine, simultaneously in vitro and in vivo. PMID- 7995073 TI - The effect of recurrent pterygium on corneal topography. AB - Pterygium is known to cause corneal topographic changes that can result in decreased visual acuity. We present a case of recurrent pterygium causing blurred vision and diplopia, and document the corneal topographic changes, showing astigmatism of 15 diopters induced by lateral gaze, prior to surgical excision. PMID- 7995074 TI - Limbal conjunctival autograft in a subacute alkaline corneal burn. AB - Persistent epithelial defects are a common complication after severe alkaline corneal burns. Chemical damage to the limbal area destroys the stem cells that play a key role in corneal reepithelialization. Limbal conjunctival autograft transplantation has been proposed as a treatment to replace damaged limbal stem cells and promote epithelial healing. We report a case of a persistent epithelial defect after a severe alkaline corneal burn that was successfully treated 6 weeks after the injury with limbal autograft transplantation. Impression cytology provided valuable information for locating the healthy and damaged limbal tissue involved in the transplantation. Two weeks postoperatively the epithelial defect was completely healed, stromal vascularization was regressed, and visual acuity was improved. PMID- 7995076 TI - Society of Critical Care Medicine. Critical care by design. 24th educational and scientific symposium. January 31-February 4, 1995, San Francisco, California. Program and abstracts. PMID- 7995075 TI - Bilateral giant papillary conjunctivitis related to glaucoma drainage surgery blebs. PMID- 7995078 TI - Analysis of Epstein-Barr virus BamHI F DNA fragment in nude mouse-passaged nasopharyngeal carcinoma tissues. AB - Two nude mouse-passaged nasopharyngeal carcinoma (NPC) tissues, NPC-295 and NPC 306, were different in ability to transform cord blood lymphocytes and contained Epstein-Barr virus (EBV) genomes with difference in BamHI F DNA fragment. Four clones containing DNA sequences of the BamHI F fragment (54,853-62,249) were obtained from genomic libraries of NPC-295 and NPC-306 and their partial restriction enzyme maps and sequences were determined. The restriction enzyme maps of EBV DNA at the BamHI F fragment in NPC-295 and NPC-306 appeared to be similar to that of EBV B95-8 strain. However, 8 nucleotide differences were revealed between NPC-295 and the B95-8 strain when 566 nucleotides (55,405 55,970) were compared, and 15 out of 677 nucleotides analyzed (55,410-56,086) were different between NPC-306 and B95-8. PMID- 7995077 TI - Sequence analysis of nucleocapsid and partial envelope genes of the hepatitis C virus derived from an aboriginal asymptomatic carrier. AB - Two overlapping cDNA fragments of the 5'-terminal region of the hepatitis C virus (named as HCV-B) were cloned by reverse transcription-polymerase chain reaction (RT-PCR). The consensus nucleotide sequence of the 1101 nucleotide length was constructed from the sequences of at least three independent clones of each one of these two amplified overlapping HCV cDNA fragments. By comparison with other HCV strains isolated from different countries, the 5' non-coding region was almost identical, with only 1 difference in 90 nucleotides, and the homology of the putative nucleocapsid gene was found to be quite conservative, with a similarity of 90-96% and 96-97% at the nucleotide and amino acid levels, respectively. The homology of the down-stream region which encodes a putative envelope protein showed a low degree of identities (71.5% and 76.7% compared with American HCV-1 strain) at the levels of nucleotide and amino acid. On the other hand, it was similar to the Taiwanese HCV-T strain and the Japanese major J1 strain; the homology was about 93% at both levels of nucleotide and amino acid. This finding led to a conclusion that the HCV-B strain is closely related to the major HCV genotypes as HCV-J1 and HCV-T, isolated in Asian area. PMID- 7995079 TI - Isolation and characterization of Aeromonas from seafoods in Taipei. AB - A total of 124 fresh seafoods and 158 processed seafoods collected from the retail markets and supermarkets in Taipei were tested for the contamination with motile Aeromonas spp. Of the fresh seafoods analyzed, 88% displayed the presence of Aeromonas. The isolation rates of various samples were as follows: 100%, freshwater fish; 95%, seawater fish; 78%, fish fillets; 84%, shrimp and crab of the crustacea group; 83%, bivalve shellfish and 84%, non-bivalve shellfish of the mollusca group, and 100%, seaweed. Of the 158 processed seafoods, 11% were contaminated by Aeromonas. The isolation rates were as follows: 0%, canned, dried, or frozen fresh seafood; 18%, salted seafood; 30%, fish cake; 7% vacuum packaged fish cakes; 14%, frozen seafood dumplings; 8%, cooked seafoods. One hundred and eighty-three Aeromonas strains isolated in this survey were characterized to species level and tested for their ability to produce beta hemolysin. Ninety-eight percent (98%) of the A. hydrophila produced beta hemolysin on 5% blood agar, 94% of the A. sobria and 33% of the A. caviae produced beta-hemolysin. Thus it is likely that fresh seafoods are potentially significant sources of the virulent Aeromonas species and may play an important role in the epidemiology of Aeromonas-associated gastroenteritis. PMID- 7995080 TI - Measurement of anti-endothelial and anti-cardiolipin autoantibodies and intercellular adhesion molecules-1 in patients with systemic and cutaneous vasculitis. AB - Two types of autoantibodies and intercellular adhesion molecule-1 (ICAM-1) were measured in patients with vasculitis. There were 13 patients with systemic vasculitis, and 12 with cutaneous vasculitis. The measured antibodies included antiendothelial cell antibodies (AECA) and anti-cardiolipin (ACL) antibodies of three isotypes. Results showed that patients with systemic vasculitis had elevated levels of ICAM-1 and IgG isotype ACL antibodies. Higher levels of ICAM-1 and IgG isotype ACL antibody were found in patients with systemic vasculitis than in those with cutaneous vasculitis. Levels of ICAM-1 and IgG isotype ACL antibodies also decreased after disease activity subsided in patients with systemic vasculitis. Measurement of ICAM-1 and autoantibodies may be useful in evaluating the extent of involvement, and for following the disease course. PMID- 7995081 TI - [Definition and calculation of case figures according to the DKI, Gebera, GSbG and IfG report (4 February 1994 status)]. PMID- 7995082 TI - [Lesions of the bile ducts in open cholecystectomy]. AB - The incidence of bile duct injuries during open cholecystectomy is around 2/1000. The most common lesion is complete divisions of the common bile duct, followed by partial divisions, stenoses or obstructions. The therapy of the lesions recognized intraoperatively is end-to-end anastomosis or, in the case of greater defects, hepaticojejunostomy. Strictures manifesting while after cholecystectomy can primarily be treated endoscopically, in divisions of obstructions hepaticojejunostomy is indicated; in high lesions the Hepp-Couinaud approach can be advocated. PMID- 7995083 TI - [Bile duct lesions in laparoscopic cholecystectomy]. AB - Laparoscopic cholecystectomy is both resulting in a slightly higher incidence of biliary lesions and a change of prevalence of the type of lesions. Damage to the biliary system occurs in 4 different types: The most severe case is the lesion with a structural defect of the hepatic or common bile duct with (IVa) or without (IVb) vascular injury. Tangential lesions without structural loss of the duct should be denominated as type III (IIIa with additional lesion to the vessels, type IIIb without). Type II comprehends late strictures without obvious intraoperative trauma to the duct. Type I includes immediate biliary fistulae of usually good prognosis. The increasing prevalence of structural defects of the bile ducts appears to be a peculiarity of laparoscopic cholecystectomy necessitating highly demanding operative repair. In the majority of cases, hepatico-jejunostomy or even intraparenchymatous anastomoses are required. Adaptation of well proven principles of open surgery is the best prevention of biliary lesions in laparoscopic cholecystectomy as well as the readiness to convert early to the open procedure. PMID- 7995084 TI - [Possibilities of endoscopy in bile duct lesions]. AB - Biliary duct injuries are occasional complications of cholecystectomy, encountered especially during early experience of laparoscopic cholecystectomy. Beside surgical reintervention, several promising endoscopic therapeutic procedures are available. Endoscopic papillotomy, possibly in combination with the placement of a drain, brings about occlusion of biliary leakage and fistula in 80% of cases. Strictures and stenoses of biliodigestive anastomoses can be treated using endoscopic transpapillary or, additionally, transhepatic percutaneous techniques. The results are comparable to those of surgery with lower rates of complications. For final judgement, however, a longer period of observation is necessary. At the moment non-surgical procedures are to be considered for patients at high risk from surgery and patients with recurrent stenoses after surgical interventions. Management of choledocholithiasis, complicating cholecystolithiasis, is becoming more and more a task for the endoscopist, at least at the present stage of evolution of laparoscopic cholecystectomy. Endoscopic bile duct clearance with or without percutaneous clearance, if necessary in combination with modern techniques of lithotripsy, is successful in almost all cases. However, the indications for risky and time consuming procedures should always be discussed between surgeons and internists. PMID- 7995085 TI - [Bile duct lesions in liver trauma]. AB - Injuries of the biliary tract remain an important concomitant lesion following liver trauma. Intra- and extrahepatic bile duct injuries differ substantially in etiology and choice of surgical procedure. Intrahepatic bile duct injuries gain clinical relevance postoperatively following primary surgical liver treatment. Characteristic consequences of intrahepatic bile duct injuries are: infected necrosis, abscess, bilious fistula, bilhemia, hemobilia and biliary duct stricture. In contrast, concomitant organ or vessel injury are of primary importance in extrahepatic biliary duct injury. Lesions of the distal biliary duct, always associated with duodenal or pancreatic injury, remains a particular thrill in general surgery. The approach to surgical treatment in case of biliary duct injury and its consequences are outlined and discussed in detail. PMID- 7995086 TI - [Risks of radical treatment in pylorus preserving duodenopancreatectomy in ductal carcinoma]. AB - Between 1986 and 1993 fifty-two patients with ductal adenocarcinoma of the pancreatic head underwent pancreatoduodenectomy, 34 in a standard Whipple technique (Whipple), 18 since 1990 preserving the pylorus (PPPD). Operating time was significantly longer for Whipple compared to PPPD (5.5 +/- 1.4 vs. 3.8 +/- 1.0; p < 0.01). Postoperative morbidity (32 vs. 56%) resulted to 50% after PPPD of early postoperative delayed gastric emptying. Hospital mortality was 6% vs. none, respectively. Histopathologic workup of 28 node positive Whipple specimens revealed node involvement in only 11% along the stomach (1) or the pyloric region (2), but in these cases tumors had obviously close relation to the gastric outlet as the reason to chose Whipple. Actuarial survival was very similar in both groups, being 41 vs. 53% at one year, 13 vs. 18% at two years, and only 3.3% at five years for the whole cohort. In conclusion distal gastric resection in Whipple's procedure in ductal carcinoma is oncologically not effective. There is no hazard for survival relating to the preservation of the pylorus. Therefore PPPD as the technically less expensive and for nutritional status more beneficial operation should be the procedure of choice also for this type of tumor. PMID- 7995087 TI - [Candida infection in surgery]. AB - Candida sepsis in surgical patients is rare, but accounting for a high lethality. The diagnosis of a candidemia is based by most authors upon two positive blood cultures in 24 h or on proof of fungi in an organ parenchyma or a normally sterile body cavity. The risk factors for the development of a candida sepsis are administration of broad spectrum antibiotics, invasive monitoring, underlying diseases affecting the immune response and surgery itself. We have checked the charts of 22,740 patients of our clinic from 1987-1992. We found 11 patients (6 male, 5 female) with a mean age of 53.2 (34-76) years with a candida sepsis. The known risk factors for the development of a candida sepsis could be confirmed: broad spectrum antibiotics 100%, invasive monitoring 100%, condition after operation 64%, nasogastric tube 54%, condition after endoscopy 45%, steroid medication 36%. Lethality was 27% (3/11); two out of three patients with a multiple organ system failure died. Recently, it has been shown that mortality was associated with older age and concomitant multiple organ system failure. The treatment of choice for fungal sepsis is intravenous amphotericin B. Finally therapeutic guidelines, the indication for a selective bowel decontamination and the question of prophylaxis with antifungal agents in all postoperative patients are discussed. PMID- 7995088 TI - [Surgical therapy of high grade stenoses of the carotid artery. Choice of procedure and results]. AB - During the last 10 years 1514 endarterectomies of the carotid artery were performed by 9 surgeons. Complication rate was 3.6%, perioperative stroke incidence 3%, and lethality rate 1.1%. The results show, that conventional endarterectomy with obligate use of intraluminal shunt is a save management in therapy of severe stenosis of the carotid artery. PMID- 7995090 TI - [Primary and secondary interventions--a concept in surgical documentation]. AB - Nowadays systematic documentation of surgical procedures is absolutely necessary in all departments of surgery and will soon be required by law. Therefore code systems are essential. Amongst numerous systems the ICPM-GE classification has been chosen as basis. In the department for abdominal and transplantation surgery at Hanover Medical School the ICPM-GE classification has been extended by a concept of coding main and suboperations. This concept considers the fact that in an individual patient the surgical procedure may consist of different and standardized suboperations. This concept widens and simplifies the possibility of documentation considerably. PMID- 7995089 TI - [Complications after 1,000 laparoscopic cholecystectomies]. AB - Between November 1990 and November 1993 we performed 1000 laparoscopic cholecystectomies. The conversion rate was 1%. Also the rate of relaparotomies was 1%. Postoperative complications occurred in 5%. Intraoperative problems are described and analysed. We had no bile duct injuries in our series. One 87-year old patient died on the fourth postoperative day due to mesenterial ischaemia. PMID- 7995091 TI - [Indications and technique of retro-ileal colorectal anastomosis after expanded left-sided hemicolectomy]. AB - Retroileal colorectal anastomosis following a complete resection of left-sided colon was performed in 28 patients with differing diseases of the colon. Concerning the rate of leakage of anastomosis dextraposition appeared to be as safe as conventional techniques. Turnbull originally created this technique to perform a tension-free anastomosis after resection of the left sided colon. In doing so the retained colon reduces the risk of incontinence especially seen with elderly patients. PMID- 7995092 TI - [Congenital duodenal obstruction in combination with heterotopic gastric mucosa in the gallbladder. Case report and etiology]. AB - A hitherto unique case of ectopic gastric mucosa of the gallbladder in combination with a congenital duodenal stenosis in an young male adult is presented and the etiology of both anomalies is elucidated. While the intestinal obstruction was confirmed prior to the operation, the diagnosis of the gastric heterotopia in the gallbladder has been established, as usually, first by histopathologic examination. Both anomalies required surgical treatment. The long standing indistinct abdominal complaints of the patient vanished after cholecystectomy and duodenojejunostomy. PMID- 7995093 TI - [Intra-abdominal foreign body granuloma--a rare complication of laparoscopic cholecystectomy]. AB - Intra-abdominally retained gallstones following laparoscopic cholecystectomy only rarely cause related morbidity. A patient is reported, in whom aseptic foreign body reaction lead to formation of a big intra-abdominal granuloma. Because of troubling symptoms laparotomy and exstirpation were required one year postoperatively. PMID- 7995094 TI - [Abdominal wall implantation metastasis 2 years after apparently uneventful laparoscopic cholecystectomy]. AB - An extraordinary rare case of implant metastasis at the laparoscopic working port, two years after an apparent uncomplicated laparoscopic cholecystectomy is presented. The histological reexamination of the gallbladder with the detection of a minimal carcinomatous lymphangiosis in newly prepared sections, the exclusion of other primary tumors and also the tumor-free interval of six months until now, after radical excision of the abdominal wall, are strongly suggestive for an intraoperative tumor cell dissemination into the abdominal wall by a histologically unrecognized carcinoma of the gallbladder. PMID- 7995095 TI - [Asymptomatic aneurysm of the superior mesenteric artery]. AB - The aneurysm of the superior mesenteric artery is a rare diagnosis also among the group of the aneurysms of the visceral arteries. Usually it is discovered already in the state of asymptomatic aneurysm. In accordance to size and localisation an elective operation should be performed, respecting the principles of vascular surgery. We report on an own case. PMID- 7995096 TI - [Measuring device for temperature measurement of solutions in surgery. Brief report of experiences over 38 years]. PMID- 7995097 TI - [From Carl Ferdinand von Graefe (1787-1840) to Gustav Biedermann Gunter (1801 1866) and his school]. AB - A for the most part unknown surgical school in Germany is presented. She begins and ends in Saxony and reaches from the 18th to the begin of the 20th century. The protagonists of this school are Carl Ferdinand von Graefe and Gustav Biedermann Gunther. Their characteristics are a strict indication, the surgery of skin, bones and joints as well as the ambulance surgery. Beside plastic surgery this school brought out many other specialties too. PMID- 7995098 TI - [Easy-flow drainage after laparoscopic cholecystectomy]. PMID- 7995099 TI - [Robert de Vernejoul (1890-1992)]. PMID- 7995100 TI - [What is the role of anesthesia in perioperative morbidity and mortality?]. AB - Recent surveys, especially in Britain and in Finland, have completed and updated a survey on anaesthesia-related morbidity and mortality that was carried out under the auspices of the French institute for health and medical research a decade ago. Severity of the patient's condition remains the key factor, along with the extent of surgery, while the improvement of safety conditions in anaesthesia through standards and recommendations is beginning to produce results. PMID- 7995101 TI - [General principles for the choice of antibiotics in surgical prophylaxis (analysis of a consensus conference)]. AB - A consensus conference on antibiotic prophylaxis in a surgical environment, organized in December, 1992 by the French Anesthesiology and Intensive Care Society, allows assessing the usefulness, safety, cost and indications of antibiotic prophylaxis by answering the major questions asked: Which surgery should benefit from antibiotic prophylaxis? What are the practical modalities of prescription? What are the reasons of the choice? What is the economic and environmental impact of antibiotic prophylaxis in surgery? PMID- 7995102 TI - [Current trends of postoperative analgesia]. AB - After being neglected for a long time, postoperative analgesia is developing considerably at present. A wide range of resources, including antipyretics, nonsteroid anti-inflammatories, agonist-antagonists and morphinic agents allow to great variations of sensibility between individuals. New techniques such as patient-controlled analgesia and spinal morphine therapy are becoming essential for intense pain. New concepts are appearing, such as treatment units for acute pain, while others are gaining new momentum, like the prophylaxis of postoperative pain. PMID- 7995103 TI - [Current data on the screening of malignant hyperthermia during anesthesia]. AB - A rare complication of general anesthesia, malignant hyperthermia is nonetheless very topical because it causes the death of young, healthy subjects who most often undergo surgery with no vital risk. Screening, an essential means of achieving riskless anesthesia, is based on testing on fresh biopsy specimens of muscle. The current state of knowledge, especially the progress made in genetics, will be commented. PMID- 7995104 TI - [Associated cancers of the esophagus and the lung]. AB - The combination of cancers of the esophagus and of the ENT region has been extensively studied. Strangely enough, only a few cases of associated cancers of the esophagus and of the lung are reported in the literature. The authors report about 38 cases, including 21 with synchronous tumors and 17 with metachronous tumors. The bronchial cancer has always been discovered on systematic search during pre- or postoperative checkups in patients with cancers of the esophagus. Conversely, this search does not seem to have been made in patients with lung cancer: the cancer of the esophagus was always revealed by dysphagia. Double exeresis was performed in 19 patients (50%). There was no postoperative death. The duration and quality of survival were markedly better than in non-operated patients. PMID- 7995106 TI - [Considerations on lymph node excision in the surgery of stomach cancers]. AB - The use of extensive lymphadenectomy is based on a historical comparison of results before 1950, when only subtotal gastrectomy was used, and after 1950 when variably extensive lymphadenectomy was associated to visceral exeresis. At the beginning, we involved neither the retroduodenopancreatic lymph nodes nor the juxtahilar nodes of the hepatic pedicle in this lymphadenectomy, and we actually performed only type R2 lymphadenectomy. After 1965, exeresis was extended to said lymph nodes, thus becoming a type R2-R3 operation. As far as visceral exeresis is concerned, our indication to extend exeresis has been defined according to the site of the tumor, to the degree of infiltration of the gastric wall and to the histological type, rather than to a principle. Thus we have after used subtotal gastrectomy, with 33.3% survival after five years, 30% after ten years and 29% after 12-15 years for the cases of the first period (R2 lymphadenectomy). With type R2-R3 lymphadenectomy, survival is 35.5% at five years and 32.5% at ten years. Total gastrectomy (always with splenectomy) has been performed in all cases of proximal extension, of juxtacardial and fundal location, of multifocal lesions and of poorly differentiated histological types (86 cases). During the period or R2 lymphadenectomy, we had 33.3% survival at five years and 25% at ten years, vs. 36.2% at five years and 32% at ten years in the second period. In properly indicated subtotal resection, R2 lymphadenectomy extending to some third level areas provides better survival, with acceptable morbidity and mortality.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7995105 TI - [Reoperation for locoregional recurrence of cancer of the rectum]. AB - 71 recurrences after rectal resections for adenocarcinoma have been operated upon. After 43 initial anterior resections (AR), the treatment of recurrence was in 19 patients a new resection and in 18 a simple colostomy. When the initial treatment was a Mile's operation (APR in 23 patients), it has been performed 10 new exerses and 5 electrocautery. In the whole series, mortality and morbidity were respectively 17.5 per cent and 8 per cent. After AR the long term survival was 40 months when the initial tumour was classified Dukes A, and only 12 months when it was classified Dukes B or C. After APR the median long term survival was only 12 months. 75 per cent of the recurrences are observed during the first two years after initial resection. The screening includes repeated clinical examination, CEA dosage, endorectal sonography, endoscopy and CT scan. The appreciation of extirpability requires clinical examination, CT scan, MRI imaging. The aim is 1. to avoid exploratory and/or palliative operations. 2. to appreciate operating difficulties and to choose an adequate approach. The indication of systematic enlarged resections has to be appreciated related to patient's comfort and survival. PMID- 7995107 TI - [Development of ambulatory surgery. An irreversible perspective]. AB - Whatever the social security system, the burden of health care costs is rising at an intolerable rate. It is however unacceptable to complain about a lack of resoures as long as the resources which are available are not used responsibly. Thanks to new technologies and drugs, ambulatory surgery, with its own adapted structures, can help to ensure responsible use of resources and satisfy patients, surgeons and allied health workers. Ambulatory surgery is currently expanding, especially in the U.S. (1990), where over 17 million operations are performed in an ambulatory mode, i.e. over 50% of all surgery. Hospitalization is avoided or shortened to a few hours whenever possible. Many uncomplicated surgical procedures, which are traditionally performed on an impatient basis under general anesthesia, are just as effectively and safely performed without admission to hospital. PMID- 7995109 TI - [Carpal tunnel syndrome. Can it still be a controversial topic?]. AB - The authors studied two aspects of the carpal tunnel syndrome. As far as the diagnosis is concerned, clinical signs and provocative manoeuvres compared to the accepted standard of electrophysiological studies proved to be insufficient to settle a surgical indication in 85 carpal tunnel syndromes. When surgery is needed, post-operative course is frequently bothered by pillar pain and decreased strength postponing return to manual activities. The authors performed a prospective randomized study of 3 techniques in 251 carpal tunnel releases: classical technique, Agee endoscopic technique and anterior ligamentoplasty. Strength was only improved by the last technique. The only advantage for the endoscopic technique was greater post-operative comfort. PMID- 7995110 TI - [Annular stenosis of the main bile duct after laparoscopic cholecystectomy]. AB - Although celioscopic cholecystectomy provides acknowledged advantages, lesions of the common bile duct appear to be more frequent with this technique than with laparotomy. Two cases of annular stenosis of the common bile duct after celioscopic cholecystectomy are presented. Evidence of their ischemic origin is available, and they lead to reflexions on the use of monopolar coagulation. In both cases, the stenosis was repaired surgically, with resection and anastomosis in one case and with a hepaticojejunal anastomosis in the other. Laying an endoprosthesis as used in case 2 seems to be interesting as a temporary solution to prepare for surgery. PMID- 7995108 TI - [Beating-heart myocardial revascularization without extracorporeal circulation. Indications, technique and 1st results of a series of 98 cases]. AB - The authors present a series of 98 aorta-coronary bypass procedures without the help of Extracorporeal Circulation. Indications and technique are detailed. There was no hospital mortality and short-term results are satisfactory. This technique, feasible in about 10% of all cases, should be considered especially in old patients, in case of chronic renal insufficiency and in redo surgery. PMID- 7995112 TI - [Colonic perforation and coloscopy. Apropos of a communication by J. Hureau et al., 9 December 1992]. PMID- 7995111 TI - [Ambulatory surgery, the French surgical patient and his surgeon.Apropos of a communication by Cl. de Lathouwer, 13 January 1993]. PMID- 7995113 TI - [Locoregional recurrence of surgically removed rectal cancers. Apropos of the communication by M. Guivarc'h et al. Meeting of 13 January 1993]. PMID- 7995114 TI - [Common bile duct stenosis after celioscopic cholecystectomy. Apropos of the communication by P. Vayre et al. Meeting of 27 January 1993]. PMID- 7995115 TI - [Production of oxygenated free radicals and the role of exogenous antioxidants in liver transplantation in rats]. AB - It has been suggested that, in transplantation organs, the lesions observed after conservation then reperfusion could be related to the formation of oxygenated free radicals. The aim of our work was first to verify the hypothesis that oxygenated free radical are formed after ischaemia-reperfusion of the liver, then to evaluate the effects of the allopurinol and glutathion, known antagonists of oxygenated free radicals, contained in the University of Wisconsin conservation fluid. The University of Wisconsin solution was compared with a Collins solution which does not contain oxygenated free radical antagonists. An orthotopic liver transplantation model was used in Wistar rats. Three groups were studied. In the control group, 5 rats underwent laparotomy then were closed with no surgery being performed. In the Wisconsin group (n = 6) and the Collins group (n = 6) the livers were washed and conserved in the corresponding solution at 4 degrees C before transplanting. Plasma levels of malonyldialdehyde, measured by high performance liquid chromatography, were used as a marker for the formation of oxygenated free radicals. Impaired liver function was assessed on the basis of mortality and serum transaminases, alkaline phosphatase and total bilirubin levels. Liver biopsy was performed at sacrifice. The level of malonyldialdehyde was significantly higher in the transplanted groups compared with the control group (p < 0.01). There was no difference between the Wisconsin and the Collins groups. Hepatic function was significantly reduced in the transplanted groups compared with the control group (p < 0.05). There was no significant difference between the Wisconsin and the Collins groups.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7995116 TI - [Functional and morphological study of the pancreatic graft after segmental heterotopic autotransplantation in dogs]. AB - Segmentary heterotopic autotransplantation of the body and tail of the pancreas, with visceral exocrine drivation and splenosplenic arterio-venous fistulation, was performed in 12 Beagle dogs. An in vivo glucose tolerance test was conducted before the transplantation and 21 days after the operation. There was a significant decrease in the k coefficient (2.884 +/- 0.234 before and 1.878 +/- 0.128 after transplantation) due to reduced peripheral glucose uptake after transplantation (p < 0.001). Overall glucose-stimulated insulin production was decreased after < 0.001). Two populations were identified retrospectively: in 7 dogs insulin response was satisfactory after transplantation (insulin production > or = 50% pretransplantation level) and in 5 the response was below 50%. Glucose tolerance was tested in vitro in the isolated perfused pancreas transplant in 9 dogs, 30 days after the transplantation. Secretory response was assessed according to the early peak of insulin secretion after glucose stimulation. The patterns of insulin secretion were not different before glucose stimulation but became statistically different after stimulation (p < 0.001). In 5 dogs, the response to in vitro glucose stimulation showed an early peak in insulin secretion and in 4 dogs the insulin response came late with no early peak. On histological examination normal (or subnormal) pancreas grafts and grafts in which extensive sclerosis impaired function could be distinguished. There was a significant correlation between the quality of function and the histology, suggesting that containing post-operative sclerosis to a minimum is an important factor in human transplantations. PMID- 7995117 TI - [Surgery of primary hyperparathyroidism by unilateral approach under local anesthesia and peroperative assay of 1-84 parathyroid hormone]. AB - By combining echography and per-operative hormone assay, surgery for primary hyperparathyroidism due to a single adenoma can be performed via a limited unilateral access route with local anaesthesia. In a recent series of 204 patients, this technique was not contraindicated in 88 (43%). The operation was successful in 81 of these (92%). In 8 cases, the operation had to be converted into bilateral cervicotomy under general anaesthesia. Six of them were successful. The overall cure rate was 98%. Peroperative assay of 1-84 parathyroid hormone is an essential element in this technique. PMID- 7995119 TI - [Classification of inguinal hernias. A personal proposal]. AB - There is no universally accepted classification of groin hernias, so related propositions are still hopeful. The authors examine the justifications and the useful criterias of such a project, the published classifications, and propose their own plan to discussion. PMID- 7995118 TI - [Posterior pharyngectomy. Reconstruction using a free antebrachial transplant]. AB - Cancers of the posterior wall of the oro or hypopharynx are rare and do not invade the larynx or the oesophageal orifice. Previously, these cancers were treated with radiotherapy alone, but since 1981 new techniques in reconstruction surgery have allowed a surgical approach. Cancerological non-mutilating exeresis is possible, but reconstruction is difficult since the flap must be very thin to allow normal food intake. In addition, flap reliability is extremely important due to the gravity of cervical salivary fistulation. We treated 15 patients with a lesion of the posterior wall of the pharynx using posterior pharyngectomy and reconstruction with a free antebrachial transplant which was revascularized and reinnervated. In two cases, the operation was performed in patients who had had previous radiotherapy. A branch of the external carotid and the internal jugular vein were used for vascular microanastomoses and reinnervation was obtained using the superficial cervical plexus. The transplant was placed over the prevertebral aponevrosis and sutured to the remaining pharyngeal mucosa. One postoperative death due to heart disease occurred at D + 11. All reconstructions were successful and two salivary fistulas on irradiated tissue closed spontaneously. Postoperative radiotherapy was performed in 11 cases (50-65 Gy) and was well tolerated. These results demonstrate that a highly flexible and thin free forearm transplant is perfectly adapted to reconstruction after posterior pharyngectomy. It is more reliable than local pediculated flaps. PMID- 7995120 TI - [Medico-legal implications of ambulatory surgery]. AB - Public opinion maintains the myth that ambulatory surgery is a benign operation. Although it may not be the ideal moment for demonstrating exceptional technical skill, there are unpredictable factors and certain limitations. To date, no specific legal concept of medical appraisal applicable to ambulatory surgery has been developed in France. Nevertheless, the nation that the surgeon is required to use all possible means is keenly accentuated because in a very short delay of a few hours the patient no longer is under direct management of the surgeon or his health care team. The aim of this work was to summarize the mandatory techniques for quality care and safety adapted to the lesions and the circumstances and taking into account accepted procedure, the current state of the art and the socio-familial environment. Two specific problems are encountered in the medical appraisal: a) defining whether the complication is inherent to ambulatory surgery, b) deciding how the responsibility could be shared. The possibility of special insurance for demonstrated non-fault surgical risk would be an elegant solution to avoid legal bias and facilitate controlled development of ambulatory surgery units. PMID- 7995121 TI - [Management of patients over 75 years of age with digestive or abdominal disease. A series of 660 cases]. AB - Over a period of 3 years, the authors cared for 660 patients over 75 years of age with diseases of the digestive tract. In 180 cases, the initial hospitalization had been previously planned and in 480 (72.7%) emergency admission was necessary. The diagnosis had not been confirmed in 90% of the emergency admissions. Half of the patients suffered from major illness (ASA III, IV). Planned hospitalization in a surgical unit involved cancer in 60% of the cases among which about one-half were colorectal cancers. In this latter group, mean hospitalization was 12 days and hospital mortality was 9.7%. For the patients with emergency admissions, diagnosis was only established after exploratory examinations (echography 296, endoscopy 205, opacification of the digestive tract 157...). No diagnosis could be established in 1.6% of the patients. Four types of emergency patients could be identified: occlusions 39.6%, painful abdomen 37%, haemorrhage 13.9% and jaundice 7.7%. In these groups, surgery was required in 64.7%, 69.1%, 72% and 40.5%, and mortality was 21.9%, 20.3%, 21.6% and 8.1% respectively. Duration of hospitalization was however similar (12 days). The overall mortality in this series was 14% (5.7% in non-operated patients and 16.7% in operated patients with a distinction between planned operations, 9.7%, and emergency operations, 20.3%). The two main risk factors were underlying disease and the need for emergency surgery. Age over 90 was also aggravated prognosis. PMID- 7995122 TI - [Organization of emergency pediatric surgery at the University Hospital in Nantes]. AB - A special emergency ward for paediatric patients was established at the University Hospital in Nantes on November 7, 1990. Both medical and surgical patients less than 15 years, 3 months of age are admitted. The initial organization of the ward (facilities personnel, on call duty) are described for the emergency paediatric surgery unit. The activity of the unit over a 4 month period (from June to September 1992) was retrospectively examined. During this period, 4,438 children were referred to the emergency ward and 2,905 (64.8%) involved a surgical pathology. The epidemiological characteristics of the patients (age, geographic origin, day and hour of admission), the causal pathology, the examinations and procedures performed, and outcome (length of stay in the ward long-term outcome) were studied. Based on these results, the authors analyzed the factors leading to dysfunction and proposed improvements in the organization of this emergency ward. PMID- 7995123 TI - [Multi-level traumatic lesions of the thoracic and lumbar spine. Value of the Cotrel-Dubousset instrumentation]. AB - Trauma of the spine involving several thoracic and lumbar vertebrae is rare (4 case in 250 spine operated in our unit from 1985 to 1990) and require difficult therapeutic decisions. The patients has one or more unstable fractures which could require 4 screw-plates that would be mechanically unsatisfactory, or an unstable fracture combined with other stable lesions requiring a mixed orthopaedic and surgical treatment that would lead to long term decubitus with a corset. The Cotrel-Dubousset system makes it possible to approach each lesion separately with segmentary instrumentation. Using different combinations of the implants we were able to obtain a construction which was both technically and mechanically satisfactory and allowed recovery of the sagittal spinal curvatures without external contention. A single operation treating all the different lesions was sufficient in 3 Frankel E patients, allowing them to return to their former activities in 3 to 6 months. The material was removed at about 20 months allowing good spinal mobility. PMID- 7995125 TI - [Clinical and histopathological analysis of 2485 gingival biopsy specimens]. AB - This study was based on a clinical and histopathological analysis of 2485 gingival biopsy specimens. sixty-nine types of gingival lesions were, identified they were 14 types of gingival inherent diseases, 29 types of tumor and tumorous lesions, 5 types of dermal and mucosal diseases, 2 types of periodontal diseases, 29 types of other diseases. Among them, eighteen have not been published by others. PMID- 7995126 TI - [Study of the stress distribution of telescope denture restoration of the periodontal tissue]. AB - The stress distribution of telescope and clasp removable partial dentures on the periodontal tissue was studied with strain gauge measuring. The results indicated that the stress distribution of telescope denture was more close to the intact dentitions than the clasp denture did. The telescope denture may produce physiological stimulation to the supporting tissues of edentulous area, hereby it may lengthen the service time of the natural teeth and slow the absorption of alveolar bone. PMID- 7995124 TI - [Robert Schumann. From music to orthopedics]. AB - The psychiatric personality of Robert Schumann has notably concerned doctors. On the contrary his right hand orthopedic impairment seems to have been neglected. Relying on some well established facts and the fingering study of certain musical works, the authors put forward a plausible diagnosis and consider a treatment which would have allowed a functional rehabilitation of the great musician and nine-fingers-handed pianist. PMID- 7995127 TI - [Inhibitory effects of Na2SeO3 on Tca8113 cells in vitro and in vivo]. AB - In the study, Na2SeO3 effectively limited the growth and proliferation of Tca8113 cells both in vitro and in vivo. The response was dependent on the dose, the starting administered time, exposed length of selenium and density of inoculated Tca8113 cells. At 1 microgram/ml dose of selenium, there were remarkable inhibitory effects while no detectable inhibitory effect to L929 cells. 1 microgram/ml dose for less than 24 hours, the growth and proliferative ability of Tca8113 cells was reversal whereas more than that period, was irreversal. In vivo experiment, the morbidity of transplanted tumors was remarkably depressed with Se intraperitoneal injection. At 60 micrograms/ip dose, the weight of nude mice were not reduced and the pathological changes in liver and kidney had not found. PMID- 7995128 TI - [Occlusal contact changes before and after orthodontic treatment of TMJD patients in children and adolescents]. AB - Occlusal contacts were examined in a sample of 32.8-17 Years old TMJD patients before and after orthodontic treatment. Computer-aided video system was applied to the silicone occlusal record obtained in the intercuspid position to assess the quantitative and qualitative changes of occlusal contacts. The results showed that after orthodontic treatment, the mean number of contacts on anterior teeth decreased, the mean area per contact decreased, the location of contacts on centric stops increased and the contacts on inclined plane were decreased. All of these indicated that the occlusal stability increased after orthodontic treatment. PMID- 7995129 TI - [Tuberculosis of the parotid glands]. AB - 41 cases of intraparotid lymph node tuberculosis and 51 cases of parotid tumors were studied. The authors suggest the following points for differential diagnosis: Clinically, intraparotid lymph node tuberculosis has a rapid onset, pustulation, regional lymphade nopathy, with a history of TB or contact with tuberculosis and low-grade fever. In most cases, the nerves function normal. Sialograms show no signs of branch ducts twist and irregular stricture and dilation. The diameter of exudative contrast mass could be more than 1 cm, but it does not exudate along the ducts. The posterior margin of ascending ramus does not show deformity. Calcification of cervical lymph nodes could be seen. If the tuberculosis mass is small, it is hard to be distinguished from tumor on sialograms. The clinical features are important in the diagnosis. PMID- 7995130 TI - [The EDAX and tetracycline vital stain investigations of the condylar remodelling after the mandibular functional protrusion in young rat]. PMID- 7995131 TI - [Immediate reconstruction of mandibular defects following tumor surgery with Ti plate system]. AB - In this paper, 31 cases with lower jaw defects (disarticular of TMJ, 9; conservation of TMJ, 8; defects of mandibular arch, 14) were immediately reconstructed following tumor-surgery with plate, and combined with bone graft for some of cases. Results demonstrated the remarkable clinical value of this method in improving post-operation function and facial deformities, even though there exist problem such as healing, occlusion and loose of plate. In addition, the key technique procedures were discussed involving in operation. PMID- 7995132 TI - [Artery supply of the lip and palate in normal and cleft patients]. AB - 50 normal and 10 cleft lip and palate head and neck specimens were studied by dissection and arteriography. The results are as follows: 1. In unilateral complete cleft lip, the superior labial artery runs along the labial margin and cleft edge, ending in base of nasal wing on the lateral side. In the medial side, upper labial artery ends in the base of the columella. 2. In the bilateral complete cleft lip, artery supply of superior lip is similar to the lateral side of unilateral complete cleft lip. The artery supplying the philtrum and premaxilla comes from the posterior septal artery, anterior ethmoid artery, nasal alar artery and/or lateral nasal artery. 3. Normal palate is supplied by six pairs of arteries. They are greater and lesser palatine artery, lesser palatine artery, nasopalatine artery, ascending palatine artery, ascending pharyngeal and palatine, artery tonsillar artery. In the cleft palate, the anterior branch of the ascending palatine artery becomes smaller and the posterior branch has shifted forward and runs forward along the cleft edge. The palatine branch of the ascending pharyngeal does not run along the palato--pharyngeal muscle, but descends from the base of skull along the levator palate muscle to the soft palate. PMID- 7995133 TI - [A posteroanterior cephalometric study of facial asymmetry]. PMID- 7995134 TI - [Pathological basis of multiple organ injures in maxillofacial high velocity missilty wound: an experimental study]. PMID- 7995135 TI - [Anatomical observation of the orbicularis oris muscle in cleft lip]. PMID- 7995136 TI - [The effect of individual anterior crossbite on functions of stomatognathic system]. PMID- 7995137 TI - [Pathomorphological and immunohistochemical study of verruciform xanthoma]. PMID- 7995138 TI - [Study on animal model of periodontitis]. PMID- 7995139 TI - [Influence of cavity width and depth on fracture resistance of preparation]. PMID- 7995140 TI - [Radiobiology of normal oral and maxillofacial tissue]. PMID- 7995141 TI - [The relationship between protrusive condylar and incisal path]. AB - The protrusive condylar and incisal sagittal paths from 70 normal subjects were studied with MT1602. The results showed that the correlation rate between the inclination of condylar and incisal guidance was 0.49 (P < 0.01). But the results from multivariate analysis showed the primary affecting factor on condylar guidance was the face angle, whilst the incisal guidance was mainly influenced by the upper and lower front teeth relationship. PMID- 7995143 TI - Continence disorders after anal fistulotomy. AB - PURPOSE: This study was designed to detect factors that predict the occurrence of continence disorders after anal fistulotomy. METHODS: A retrospective study of the charts of 312 patients was undertaken. A questionnaire was sent to all patients, with a response rate of 90 percent. RESULTS: Minor continence disorders occurred in 73 patients, incontinence did not occur. Multivariate analysis (chi squared test) was performed showing that extensions (P = 0.008), location (P = 0.03), and level (P = 0.029) of the anal opening appeared to be independent factors. CONCLUSION: Patients with high openings, posterior openings, or fistula extensions are at risk to develop continence disorders after anal fistulotomy. PMID- 7995142 TI - Preoperative staging of rectal cancer by endoluminal ultrasound vs. magnetic resonance imaging. Preliminary results of a prospective, comparative study. AB - PURPOSE: The aim of this study was to compare the value of endoluminal ultrasonography (ELUS) with magnetic resonance imaging (MRI) for preoperative staging of rectal carcinoma. METHODS: Thirty-seven consecutive patients were examined by ELUS and MRI. Imaging results were compared with pathohistologic studies. A tumor extending beyond the bowel wall was considered to be "positive" and one within the bowel wall was considered "negative." Lymph node involvement was considered present if nodes equal to or greater than 5 mm in diameter were found in the perirectal tissue. For evaluating the differences between the two methods, the Mc Nemar test was performed. RESULTS: T-Staging was correct in 88.2 percent (30/34) of patients by ELUS and in 82.3 percent (28/34) by MRI (difference not significant). N-Staging was correct in 80 percent (20/25) by ELUS and in 60 percent (15/25) by MRI (difference of borderline significance). A comprehensive preoperative staging (T + N) was made correctly in 68 percent (17/25) by ELUS and in 48 percent only (12/25) by MRI (difference not significant). CONCLUSIONS: We suggest that ELUS and MRI must be evaluated within the framework of established parameters when treatment modalities such as preoperative radiation therapy and local or radical surgical approach must be decided. PMID- 7995144 TI - Experimental laser anastomosis of the colon. Long-term results and histologic findings after laser closure of colotomies. AB - PURPOSE: Our previous experimental work showed the feasibility of colon anastomosis using laser; however, it also revealed a narrowing tendency after laser anastomosis. Long-term observation of the postoperative course of laser anastomosis was planned to assess this point. METHODS: Clinical observation and histologic examination of transverse colotomies (average, 21.2 mm) in New Zealand white rabbits (n = 12) closed with a 1,064-nm neodymiumyttrium aluminum garnet (Nd:YAG) laser were carried out up to the third postoperative month, compared with closure of colotomies using a single layer of interrupted sutures of 5-0 Maxon (Davis & Geck, Pearl River, NY) in a control group (n = 12). RESULTS: Whereas the narrowing tendency was observed up to one month after the operation in the laser group (P < 0.05), it disappeared at three months following the operation without causing abnormal weight loss during the experiment. Simultaneously, there was again a marked decrease in adhesion formation following laser anastomosis (P < 0.01). Collagen fibers were observed earlier in the laser group. CONCLUSIONS: An earlier commencement of collagen synthesis after laser anastomosis was proved. A narrowing tendency, which was observed from seven days to one month postoperatively, disappeared at three months after laser anastomosis without exerting any effect on growth. PMID- 7995145 TI - Adjuvant preoperative radiotherapy for locally advanced rectal carcinoma. Results of a prospective, randomized trial. AB - PURPOSE: A prospective, randomized clinical trial was conducted by the Northwest Rectal Cancer Group to study the effects of preoperative radiotherapy given one week before surgery in locally advanced (tethered or fixed) rectal carcinoma. METHODS: A total of 284 patients were entered into the trial between 1982 and 1986; 141 were allocated to receive surgical treatment alone, and 143 were allocated to receive preoperative radiotherapy. A 10 x 10 x 10 cm volume in the posterior pelvis, centered on the tumor, was irradiated at a dose of 20 Gy, divided into four daily fractions of 5 Gy each. RESULTS: No differences were observed in any of the clinicopathologic variables in the two arms of the trial; there were no striking down-staging effects in the irradiated tumors. After a minimum follow-up period of 96 months, the overall and cancer-related mortality rates were similar in both arms of the study (P = 0.21 and P = 0.09, respectively). There was a highly significant reduction in local recurrences in the irradiated group (12.8 percent x-ray therapy vs. 36.5 percent surgery; P = 0.0001). The majority of local recurrences after preoperative radiotherapy occurred inside the radiotherapy field (10 cases; 7 percent), with only six cases (5 percent) outside the field. No significant difference was observed in the rates of distant metastasis between the two treatment groups (P = 0.73). CONCLUSIONS: Although there is no statistically significant survival benefit in the whole series, there is a survival benefit for the subset of patients considered by the surgeon to have undergone a curative operation. We recommend that this form of adjuvant therapy should be offered to all patients with locally advanced rectal cancer who are to undergo radical surgery. PMID- 7995146 TI - Histoanatomy of anal glands. AB - PURPOSE: This study was designed to investigate the histology of adult anal glands using conventional as well as immunochemical methods. METHODS: Fifteen fresh human ani were prepared and stained with conventional and immunohistologic stains. RESULTS: The median number of anal glands in each anus was six (range, 3 10). Sixty-eight (80 percent) of 85 anal glands found were submucosal in extent, seven (8 percent) extended to the circular internal sphincter, seven (8 percent) to the longitudinal internal sphincter, two (2 percent) to the intersphincteric space, and only one (1 percent) penetrated the external anal sphincter. Ampulla like dilations were noted in anal glands from ten patients only, occurring at the submucosal level in seven ani and at the circular internal sphincter in three ani. Lymphocytic infiltrations were noted around the glands in all ani studied. Mucus-secreting cells were found in all ani, and many glands showed the presence of intraluminal secretions. Immunostaining for smooth muscle actin showed the presence of one to two cell layers of myoepithelial cells surrounding all anal glands. CONCLUSIONS: Anal glands are definite preformed structures with secretory activity. PMID- 7995147 TI - Prognostic predictors in colorectal cancer. AB - PURPOSE: Better prognostic predictors in colorectal cancer than the Dukes stage are necessary for individualized therapy and follow-up. METHODS: Survival among 212 patients operated on for colorectal cancer was examined regarding various clinical, histopathologic, cellular, and serologic tumor characteristics. RESULTS: Beside the Dukes stage, which was the most powerful variable, the erythrocyte sedimentation rate, leukocyte blood count, alkaline phosphatase, aspartate aminotransferase, six different serum tumor markers, number of small blood vessels, and age were found to be significantly associated with survival. The leukocyte blood count, alkaline phosphatase, and aspartate aminotransferase retained their significance in a multivariate model including tumor differentiation, local tumor stage, and age. Inclusion of tissue polypeptide antigen, the most powerful tumor marker in the multivariate model, showed that only the tumor stage, tissue polypeptide antigen, and age were statistically significantly correlated to survival. This was valid both for the group of patients considered as potentially curable and for those who potentially have been cured (Dukes Stages A-C). CONCLUSIONS: A great number of prognostic predictors failed to discard Dukes stage as the best one. One serum tumor marker, tissue polypeptide antigen, contains independent additional prognostic information. PMID- 7995148 TI - Decrease in the anorectal pressure gradient after low anterior resection of the rectum. A study using continuous ambulatory manometry. AB - PURPOSE: Changes in anorectal function after low anterior resection of the rectum (LAR) often lead to symptoms of urgency and frequency of defecation, the anterior resection syndrome. It has been reported that preservation of part of the rectum improves clinical results, but why this should be remains unclear. METHODS: We have carried out continuous ambulatory manometric studies in two groups of patients: 11 patients, a median of 11 (range, 5-96) months after LAR, in whom the median anastomotic level above the anal high-pressure zone was 0 (range, 0-2) cm; 9 patients, a median of 6 (range, 3-12) months after sigmoid colectomy, in whom the rectum remained in situ and who acted as controls. RESULTS: Comparing the LAR group with controls, resting anal pressures were lower, median 68 (range 27-102) cm H2O vs. 95 (45-116) cm H2O (P < 0.05), and neorectal pressures were higher, 25 (0-48) cm H2O vs. 10 (0-10) cm H2O (P < 0.01). Thus the anorectal pressure gradients were less, 34 (0-74) cm H2O vs. 81 (35-113) cm H2O (P < 0.01). Slow wave activity in the anal sphincter was present in six patients (55 percent) after coloanal anastomosis and eight patients (89 percent) after sigmoid colectomy. Sampling episodes were seen in only two patients (18 percent) after coloanal anastomosis and five patients (56 percent) after sigmoid colectomy. When clinical endpoints were compared (LAR vs. controls), bowel frequency in 24 hours was higher, 5 (3-8) vs. 2 (1-3) (P < 0.01); fecal leakage was more common, affecting seven patients (64 percent) vs. one patient (11 percent) (P < 0.05), and urgency of defecation was also more common. CONCLUSIONS: The inferior clinical results observed after LAR compared with the results after sigmoid colectomy are thus in part because of higher neorectal pressure acting on a weakened sphincter mechanism. These observations lend support to the idea that neorectal capacity should be increased in patients who undergo low anterior resection. PMID- 7995149 TI - Management of recurrent pilonidal sinus by simple V-Y fasciocutaneous flap. AB - PURPOSE: Several methods of managing the sacrococcygeal pilonidal sinus have been described, and fervent arguments for each form of therapy can be found in the literature. Recurrence unfortunately plagues all forms of therapy, though it is evident that the lowest rates have been reported for procedures involving local flap reconstruction. We conducted this case review to evaluate the validity of a simple reconstructive procedure for recurrent pilonidal disease. METHODS: We describe the application of the V-Y fasciocutaneous advancement flap to reconstruct the defect following radical excision of recurrent pilonidal sinus in five consecutive patients. RESULTS: Tension-free closure offers the benefits of a reduction in postoperative pain, less restriction in activity, and a shorter hospital stay. CONCLUSIONS: Preliminary results offer evidence of the efficacy of the simple reconstructive procedure in the management of difficult cases. PMID- 7995150 TI - Awake epidural anesthesia is effective and safe in the high-risk colectomy patient. AB - PURPOSE: This study was designed to examine the feasibility and safety of performing open colectomy using awake epidural anesthesia in high-risk patients with comorbid illnesses. METHODS: We retrospectively compared 15 high-risk patients who underwent colectomy using awake epidural anesthesia with 17 lower risk colectomy patients who received conventional general endotracheal anesthesia. All patients were operated on consecutively during the same time period by the same surgeon. RESULTS: Based on the number of coexisting diseased organ systems and by a weighted multifactorial index of operative risk, the patients receiving awake epidural anesthesia were significantly more ill than the patients receiving general anesthesia. No differences in complications, length of operative procedure, or number of lymph nodes in cancer specimens were found between the two groups. There was a trend favoring the epidural technique when operative blood loss, length of postoperative hospital stay, and return of bowel function were considered. CONCLUSIONS: Awake epidural anesthesia is a safe and effective technique in high-risk patients undergoing colectomy and achieves an operative risk that compares favorably with healthier patients receiving general anesthesia. PMID- 7995151 TI - Ambulatory surgical hemorrhoidectomy--a solution to postoperative urinary retention? AB - PURPOSE: The most frequent complication of surgical hemorrhoidectomy is urinary retention. This study evaluates the incidence of urinary retention in a series of patients undergoing surgical hemorrhoidectomy in an ambulatory setting. METHODS: The records of all patients undergoing anorectal surgical operative procedures during the calendar year 1990 were reviewed, with particular emphasis on urinary retention and other postoperative complications. RESULTS: Of 201 patients undergoing full surgical hemorrhoidectomy by Colon and Rectal Clinic, 91 percent had operations performed on an ambulatory basis (discharge less than four hours following surgery). Of these 190 patients, only 1 (0.53 percent) required urinary catheterization during the postoperative period. CONCLUSIONS: The ambulatory setting, when combined with careful patient education and perioperative fluid restriction, allows surgical hemorrhoidectomy to be performed with a very low incidence of urinary retention to the benefit of both patient and surgeon. PMID- 7995152 TI - Clinicopathologic characteristics of large bowel cancer developing after radiotherapy for uterine cervical cancer. AB - PURPOSE: This study was designed to clarify the characteristics of large bowel cancer developing after radiotherapy for uterine cervical cancer. METHODS: A retrospective chart review was performed. RESULTS: The latent period was a mean of 20.5 years. The most common site was in the rectum (16/32). Mucin-producing carcinoma was observed in 53.1 percent, with an especially high rate of 75 percent in the rectum. Histologic radiation damage was also demonstrated at a high rate of 64.3 percent. CONCLUSIONS: It was difficult to judge from clinicopathologic findings whether large bowel cancer developed with relation to radiation effect. We emphasize, however, that the characteristics are different from ordinary large bowel cancer. Particular consideration should be given to the high incidence of mucin-producing carcinoma. PMID- 7995153 TI - Role of pudendal nerve terminal motor latency assessment in constipated patients. AB - The importance of pudendal nerve terminal motor latency assessment for the evaluation of incontinence is well established. However, its role in constipated patients remains unclear. PURPOSE: The purpose of the present study was to assess the incidence of pudendal neuropathy in constipated patients and its correlation with others variables including age, sex, anal pressures, and anal electromyography. RESULTS: From 1988 to 1993, 161 patients with chronic constipation underwent pudendal nerve terminal motor latency assessment, anal electromyography, and anal manometry. The overall incidence of pudendal neuropathy was 23.6 percent; females and males had a similar incidence (24 percent vs. 23 percent, respectively; P > 0.05). Patients over 70 years old had a significantly higher incidence of pudendal neuropathy than did patients under 70 years (37 percent vs. 12 percent, respectively; P < 0.01). Patients with paradoxical puborectalis contraction on anal electromyographic assessment had a higher incidence of bilateral neuropathy, paradoxical puborectalis contraction (+)23 percent vs. paradoxical puborectalis contraction (-)8 percent, P < 0.05. Patients with pudendal neuropathy also had a higher incidence of decreased motor units potential recruitment than did patients without pudendal neuropathy (31.5 percent vs. 17 percent, respectively; P > 0.05). CONCLUSIONS: Pudendal nerve terminal motor latency assessment was able to detect unsuspected pudendal neuropathy in 24 percent of patients. This finding correlated with age and with the presence of paradoxical puborectalis contraction but not with manometric anal pressures, motor unit potentials recruitment, or the presence of polyphasia. However, the often espoused relationship between pudendal latency and external sphincter function could not be demonstrated. PMID- 7995154 TI - Adjuvant interferon for anal condyloma. A prospective, randomized trial. AB - PURPOSE: The aim of this study was to determine whether interferon combined with surgical excision and fulguration could reduce the unacceptably high rate of recurrence of anal condyloma seen after surgical extirpation. METHODS: Forty three patients with anal condyloma were prospectively randomized into two groups. Group I (n = 25) patients underwent surgical excision and fulguration immediately followed by an injection of 500,000 IU (0.1 ml) of interferon alfa-n3 into each quadrant of the anal canal. Group II (n = 18) patients underwent surgical excision and fulguration but then received four injections (0.1 ml) of saline into each quadrant of the anal canal. RESULTS: After a mean follow-up of 3.8 months, 10 of 43 (23 percent) patients developed recurrent anal condyloma. Only 3 of 25 (12 percent) interferon-treated patients had recurrences vs. 7 recurrences in 18 (39 percent) saline-treated patients (P = 0.046). Interferon was particularly effective in reducing recurrences in patients whose condylomata were present for more than six months (P = 0.04) and those condylomata that contained human papillomavirus DNA subtype 6/11 (P = 0.05). CONCLUSION: Adjuvant interferon treatment can reduce the high recurrence rate of anal condyloma seen after surgical extirpation. PMID- 7995155 TI - Early postoperative feeding. AB - PURPOSE: Our intent was to show that immediate postoperative feeding of a regular diet after elective colorectal surgery was safe, tolerable, and feasible. METHODS: This was a nonrandomized, prospective study of 38 consecutive patients who underwent elective colorectal surgery over a three-month period. Our study parameters included operative length of time, intraoperative blood loss, need for transfusions, day to flatus or defecation, ability to tolerate a diet, placement of nasogastric tubes postoperatively, and length of hospital stay. These patients were compared with patients treated by different surgeons during the same time period but fed only after return of bowel sounds or flatus. RESULTS: Thirty-one of 36 patients eventually included in this study were able to tolerate our early feeding regimen. There were a total of seven other complications that were minor and unrelated to the early feeding. Patients who tolerated early feeding had shorter postoperative length of stays, 5.7 vs. 10.6 days. Patients who tolerated early feeding had shorter length of stays than patients treated in a more conventional manner, 5.7 vs. 8.0 days. Those who did not tolerate early feeding had longer procedures and greater intraoperative blood loss. CONCLUSIONS: Early postoperative feeding is safe and is tolerated by the majority of patients. Early feeding, if tolerated, decreases length of hospital stay and may decrease health care costs. Longer operative time and increased blood loss intraoperatively may indicate a more difficult procedure and identify those patients who will not tolerate early feeding. PMID- 7995156 TI - Endocavitary irradiation. An option in select patients with rectal cancer. AB - PURPOSE: Endocavitary irradiation delivers high-dose irradiation with limited penetration and is an established modality for the curative treatment of select tumors. The purpose of this study was to review the experience from our institution with endocavitary irradiation. METHODS: All patients with rectal cancer treated with endocavitary irradiation between 1973 and 1992 were studied. Collected data included: tumor size, tumor differentiation, distance from the anal verge, mean follow-up, recurrence, and other treatments used. RESULTS: One hundred ninety-nine patients received endocavitary irradiation, with 126 treated with curative intent. No significant differences were found between groups with recurrence and no recurrence when examining tumor size, differentiation, distance from the anal verge, or follow-up. With a mean time to recurrence of 16.1 (range, 1-56) months, 37/126 patients had a recurrence, and 89/126 had no recurrence. Ten recurrences were distant, and all patients died of the disease. Twenty-seven patients had local recurrence. Following additional treatments, 14 additional patients were rendered free of disease. CONCLUSION: Endocavitary irradiation initially rendered 71 percent (89/126) free of disease. With additional treatment 11 percent (14/126) were rendered free of disease. In the subgroup of patients followed more than five years, 68 percent had no evidence of disease at follow-up after endocavitary irradiation, and 91 percent had no evidence of disease with additional treatment. Tumor size, differentiation, morphology, and distance from the anal verge did not influence recurrence. Debulking or surgical excision before endocavitary irradiation did not increase recurrence. Diligent long-term follow-up and a liberal policy to biopsy suspicious areas may increase the salvage rate. PMID- 7995157 TI - Biofeedback training is useful in fecal incontinence but disappointing in constipation. AB - BACKGROUND: Successful biofeedback therapy has been reported in the treatment of fecal incontinence and constipation. It is uncertain which groups of incontinent patients benefit from biofeedback, and our impression has been that biofeedback is more successful for incontinence than for constipation. PURPOSE: This study was designed to review the results of biofeedback therapy at the Lahey Clinic. METHODS: Biofeedback was performed using an eight-channel, water-perfused manometry system. Patients saw anal canal pressures as a color bar graph on a computer screen. Assessment after biofeedback was by manometry and by telephone interview with an independent researcher. RESULTS: Fifteen patients (13 women and 2 men) with incontinence underwent a mean of three (range, 1-7) biofeedback sessions. The cause was obstetric (four patients), postsurgical (five patients), and idiopathic (six patients). Complete resolution of symptoms was reported in four patients, considerable improvement in four patients, and some improvement in three patients. Manometry showed a mean increase of 15.3 (range, -3-30) mmHg in resting pressure and 35.7 (range, 13-57) mmHg in squeezing pressure after biofeedback. A successful outcome could not be predicted on the basis of cause, severity of incontinence, or initial manometry. Twelve patients (10 women and 2 men) with constipation underwent a mean of three (range, 1-14) biofeedback sessions. Each had manometric evidence of paradoxic nonrelaxing external sphincter or puborectalis muscle confirmed by defography or electromyography. All patients could be taught to relax their sphincter in response to bearing down. Despite this, only one patient reported resolution of symptoms, three patients had reduced straining, and three patients had some gain in insight. CONCLUSIONS: Biofeedback helped 73 percent of patients with fecal incontinence, and its use should be considered regardless of the cause or severity of incontinence or of results on initial manometry. In contrast, biofeedback directed at correcting paradoxic external sphincter contraction has been disappointing. PMID- 7995158 TI - Colorectal cancers of rare histologic types compared with adenocarcinomas. AB - PURPOSE: To examine clinical characteristics of colorectal cancers of rare histologic types compared with adenocarcinomas. METHODS: Review of a population based registry with complete ascertainment. RESULTS: There were 7,422 colorectal cancers, 4,900 (66 percent) colonic and 2,522 (34 percent) rectal. Two hundred fifty-five cancers (3 percent) were of nonadenocarcinoma varieties including 75 (33 percent) squamous, 74 (33 percent) malignant carcinoids, 37 (16 percent) transitional cell-like, 25 (11 percent) lymphomas, 9 (4 percent) sarcomas, and 2 (0.9 percent) melanomas. Sixty (1.2 percent) of the colon cancers occurred in the appendix, and proportionately more carcinoids accounted for these tumors. Compared with adenocarcinomas, colonic and rectal carcinoids and colonic lymphomas accounted for a larger proportion of cancers in the younger age groups. The elderly had proportionately fewer colonic carcinoids. Colonic carcinoids, rectal squamous-cell cancers, and rectal transitional cell-like cancers were more common in women. Colonic lymphomas had a worse prognosis than adenocarcinomas. Survival was better with colonic and rectal carcinoids and rectal transitional cell-like cancers than with adenocarcinomas. CONCLUSIONS: Colorectal cancers of histologic varieties other than adenocarcinoma have distinctive epidemiologic and clinical traits. PMID- 7995160 TI - Prospective analysis of colorectal carcinoma. Determination of an age-site and stage relationship and the correlation of DNA index with clinicopathologic parameters. AB - PURPOSE: A prospective study of colorectal cancer (1987-1991) using flow cytometry was performed to determine the relationship of age with DNA index (DNA I), sites of disease, Dukes stage, grade, and survival. METHODS: The flow cytometry was performed on 138 fresh, unfixed, surgical specimens using 4',6' diamidino-2-phenylindole, a DNA fluorochrome. RESULTS: The mean age was 66.9 (42.8 percent > or = 70; range, 22-92; median, 68) years, and 48.6 percent were female. The patients' stages were (in percent): A, 4.4; B, 53.0; C, 38.2; D, 4.4. Tumor grades of differentiation (in percent) were well, 14.4; moderate, 68.9; poor, 16.7; and sites (in percent) were: rectum, 19.6; sigmoid/left, 50.7; transverse/right, 29.0. Aneuploidy (DNA-I not equal to 1.0; CV, 3.5 percent) was found in 58.8 percent. Age (by decade of presentation) was compared with site and Dukes stage. Older patients had more transverse/right-sided lesions (P = 0.003). Patients with Dukes C and D tumors had a lower age (by decade of presentation) than patients with B2 lesions (P = 0.03). Age was not related to DNA-I or grade or DNA-I with sex, grade, site, stage, or survival (P > 0.05). CONCLUSIONS: This prospective study suggests that colorectal cancer tends to present at an earlier stage and in the more proximal colon in the older population. Because right-sided lesions are beyond the reach of sigmoidoscopy, these findings have prognostic and screening implications. PMID- 7995161 TI - Reappraisal of partial lateral internal sphincterotomy. AB - PURPOSE: The aim of this study was to delineate the results, mortality, and morbidity of partial lateral internal sphincterotomy for the treatment of chronic anal fissure. METHOD: A retrospective review of 500 patients undergoing partial lateral internal sphincterotomy for chronic anal fissure between 1980 and 1990 was performed. Patients were identified by a review of an office surgical ledger and included all patients whose diagnosis was anal fissure and for whom a partial lateral internal sphincterotomy was performed as treatment. RESULTS: Over an average follow-up of 5.6 years, only 1 percent of patients failed to health their fissures after performance of this operation. Minor complications included pain, pruritus, wound abscess, discharge, delayed healing, bleeding, fecal impaction, minor incontinence, and urgency and were present in 16 percent of patients, postoperatively. Two percent of patients who initially healed their fissures suffered a recurrence. Complication rates in open vs. closed sphincterotomy were 15 percent vs. 8 percent (P < 0.01). Disorders of fecal continence occurred in 8 percent of patients over the long term. CONCLUSION: Extended follow-up after partial lateral internal sphincterotomy demonstrates a higher complication rate than was seen in patients being followed for shorter periods. However, the complication of impaired fecal continence only occurred in 8 percent of our patients, compared with 15 percent reported in the current literature, although using the same evaluative criteria. Patient satisfaction with the results of surgery was 98 percent. Careful patient selection, absence of preoperative continence problems, and meticulous surgical techniques are necessary to achieve this type of result. PMID- 7995159 TI - Incidence, risk factors, and treatment of dysplasia in the anal transitional zone after ileal pouch-anal anastomosis. AB - Preservation of the anal transitional zone (ATZ) after restorative proctocolectomy and stapled ileal pouch-anal anastomosis (IPAA) for ulcerative colitis is controversial. PURPOSE: To evaluate the incidence, risk factors, and treatment options for dysplasia and/or cancer after restorative proctocolectomy and stapled IPAA. METHODS: We reviewed the records of all 254 patients operated on for ulcerative colitis who had a restorative proctocolectomy, stapled IPAA, and annual postoperative biopsies of ATZ. Follow-up studies included an annual questionnaire and physical examination. RESULTS: During a follow-up of 2.3 +/- 1.4 (mean +/- standard deviation) years, low-grade dysplasia was found in eight patients (3.1 percent), 16 (median: range, 6-56) months after surgery. Repeated biopsies revealed dysplasia in only two of eight patients, and completion mucosectomy was performed. Dysplasia in ATZ was associated with a preoperative (P = 0.02) or postoperative (P = 0.04) pathologic diagnosis of ulcerative colitis with concurrent dysplasia or cancer. No association (P > 0.05) was found between dysplasia and the following: age, sex, preoperative length of disease, use of a double-stapled versus single-stapled technique, or anastomotic distance from the dentate line. CONCLUSIONS: Incidence of low-grade dysplasia in ATZ was low. Restorative proctocolectomy with total mucosectomy of the anal canal and handsewn IPAA is recommended for patients with preoperative diagnosis of ulcerative colitis and concurrent cancer or dysplasia. Frequent follow-up with biopsies is recommended for patients with incidental finding of cancer or high-grade dysplasia after restorative proctocolectomy and stapled IPAA with preservation of ATZ. For persistent or recurrent low-grade dysplasia, we recommend a completion mucosectomy. PMID- 7995162 TI - Vaginal endosonography. New approach to image the undisturbed anal sphincter. AB - PURPOSE: Although anal endosonography provides clear images of anal sphincters, the probe in the anal canal may distort epithelial structures and sphincter muscles may be compressed, producing inaccurate muscle thickness measurements. The aim of this study is to describe a new approach using vaginal endosonography to image the anal canal undistorted. METHODS: Twenty females (10 healthy volunteers and 10 with fecal incontinence) had both anal and vaginal endosonography performed. RESULTS: The undisturbed anorectum, submucosa, anal cushions, and anal sphincter muscles were clearly visualized by vaginal endosonography, and anatomy was described. Although anal and vaginal endosonographic measurements of internal sphincter muscle thickness correlated (r = 0.83; P = 0.01), anal endosonography consistently underestimated the thickness (2.3 +/- 0.5 vs. 3.2 +/- 1.2 mm; mean +/- standard deviation). Anterior internal and external anal sphincter defects were identified accurately with both techniques. CONCLUSIONS: Vaginal endosonography is a new technique that enables accurate imaging of anal sphincters and epithelial structures at rest. In addition to making the diagnosis of anal sphincter defects, it has potential applications in the imaging of anovaginal sepsis and malignancy and possibly in understanding the pathogenesis of anal fissure and hemorrhoids. PMID- 7995163 TI - Flat adenoma-adenocarcinoma sequence in the colon of rats. AB - PURPOSE: As there is an increased awareness of the existence of a "flat adenoma adenocarcinoma sequence" in the colonic mucosa of human subjects, the aims of the study were to assess whether flat colonic adenocarcinomas in rats are also preceded by flat adenomas, as is reported in humans, and to determine the frequency of flat lesions compared with exophytic lesions in the colon of rats. METHOD: The colonotropic carcinogen 1,2-dimethylhydrazine was injected subcutaneously in 300 Sprague-Dawley rats for 27 weeks. RESULTS: A total of 358 tumors developed in 278 of the 300 rats. Of the 60 adenomas found at histology, 25 percent were flat adenomas. Of the 298 adenocarcinomas, 12.7 percent had originated in a flat adenoma. Of the 180 colonic neoplasias (adenomas or adenocarcinomas), 29.4 percent were flat neoplasias (flat adenomas or adenocarcinomas arising in a flat adenoma), and the remaining 70.6 percent were exophytic neoplasias (tubulo or villous adenomas or adenocarcinomas arising in exophytic adenomas). From the 298 colonic adenocarcinomas, 1 was a intramucosal adenocarcinoma, 87 were overt adenocarcinomas, and 90 were lymphoid-associated carcinomas; in those 298 adenocarcinomas, no preneoplastic lesion could be recorded. In 208 animals, biopsies were taken from macroscopically visible colonic lesions, and, in the remaining 70 animals, the entire colon was processed for histologic examination. Flat adenomas were found in 3.8 percent of the 208 biopsy specimens and in 10 percent of the 70 colectomy specimens. Further, of the 40 adenomas found in biopsy specimens, 20 percent were flat adenomas, and, of the 20 adenomas found in colectomy specimens, 35 percent were flat adenomas. CONCLUSIONS: The study reported herein indicates the existence of a "flat adenoma adenocarcinoma sequence" in the colonic mucosa of Sprague-Dawley rats. The flat lesions of the colon constituted approximately one-third of the total neoplastic lesions seen in the rat following injections of 1,2-dimethylhydrazine. More flat adenomas were detected at histologic examination of the entire colon than in biopsies obtained from the macroscopically visible colonic lesions. Consequently, flat adenomas may be overlooked by naked-eye examination. PMID- 7995164 TI - Crohn's disease in the Chinese population. An experience from Hong Kong. AB - PURPOSE: Crohn's disease was extremely rare among Chinese. We reviewed all cases diagnosed as having Crohn's disease during a five-year period. METHODS: A diagnosis of Crohn's disease was made only if all of the following criteria were fulfilled: 1) clinical symptom(s) and sign(s) compatible with chronic inflammatory bowel disease; 2) exclusion of intestinal infection by repeated stool cultures; 3) macroscopic features of small and/or large intestinal inflammation with skip lesion, stricture, and fistula formation; 4) histologic features of Crohn's disease, i.e., focal lymphoid aggregate, focal cryptitis, and granuloma formation; 5) clinical response to conventional therapy for inflammatory bowel disease. RESULTS: Fifteen ethnic Chinese patients were diagnosed as having Crohn's disease in this period. All patients had colitis, whereas small intestine inflammation was documented in only 47 percent of patients. Extraintestinal manifestations were uncommon except for arthropathy: ankylosing spondylitis (2), sacroiliitis (1), juvenile rheumatoid arthritis (1), and colitic arthritis (1). The majority of our patients responded to medical therapy. Surgery was undertaken in 33 percent of patients. CONCLUSION: Although there is a general increased incidence of Crohn's disease in the Western world, we too are beginning to see more cases in the Far East. Nevertheless, gastrointestinal infection with bacteria and/or parasites should still be carefully excluded in these countries. PMID- 7995165 TI - Interobserver agreement in defecography. AB - PURPOSE: This study was designed to test the reproducibility of the diagnostic assessment of defecographies in patients with a suspected disorder of defecation. METHODS: To evaluate interobserver agreement, 100 defecographic series of patients with complaints suggesting a disordered defecation were evaluated independently by three observers with a standardized questionnaire. After six weeks, a random sample of 35 of 100 defecographies was evaluated a second time with clinical data provided (history, proctologic examination). To evaluate whether the position of residual volume in the rectum would affect agreement, patients with substantial retention either in the upper or lower rectum were also evaluated separately. RESULTS: Total agreement regarding rectocele and internal prolapse was 0.81 and 0.75, respectively (1.0 = complete agreement), and was significantly higher than chance agreement. Total agreement regarding residual volume in the rectum at the end of defecography and clinical relevance of findings was not different from chance agreement, providing clinical data did not significantly improve agreement. When residual volume was situated in the lower rectum, agreement regarding incompleteness of emptying and its clinical relevance was much better (0.93). CONCLUSIONS: Interobserver agreement is good regarding the deformation of the rectum during defecography but not different from chance agreement regarding the completeness of evacuation. PMID- 7995166 TI - Therapy of anal fissure using botulin toxin. AB - PURPOSE: With chronic anal fissure, sphincterotomy to relieve sphincter spasm is the recommended therapy. This breaks the vicious circle of inflammation-pain spasm. This obvious success is weighed against the possible risk of the operation and the risk of subsequent fecal incontinence. The following report describes a therapy for anal fissure involving injection of the external anal sphincter with botulin toxin. METHODS: We have used this new method in 12 cases (7 females and 5 males; mean age, 37 years). We injected 0.1 ml of diluted toxin on both sides lateral to the fissure. RESULTS: The fissure healed thanks to a time-limited paresis of the sphincter in ten cases. In one case there was a recurrence within the first six months. Two patients could not be healed and had to undergo surgery. CONCLUSION: Injection of botulin toxin gives us a possible new mode of therapy in the treatment of chronic, uncomplicated anal fissures with increased sphincter tone. It is well tolerated, can be performed as an outpatient, does not cause any lesion of the continence organ, and subsequently does not lead to any permanent latent or apparent fecal incontinence. PMID- 7995167 TI - Seminal vesicle fistula following abdominoperineal resection for recurrent adenocarcinoma of the rectum. Report of a case. AB - PURPOSE: Fistula formation between the seminal vesicles and a pelvic abscess after abdominal perineal resection for recurrent rectal cancer is reported in a 32-year-old male previously treated with low anterior resection, chemotherapy, and radiation. METHODS: The case history was reviewed for clinical presentation, radiologic studies, and laboratory data. RESULTS: Successful management of this previously unreported complication included percutaneous abscess drainage, antimicrobial therapy, and oral administration of Proscar (Merck, Sharpe & Dohme, Rathway, NJ). CONCLUSION: Multiple factors predisposed this patient's development of a seminal vesicle fistula. These include extensive scarring from previous surgery, pelvic radiation, and an immunologically depressed status. The efficacy of Proscar in the successful management of this case remains unknown. PMID- 7995168 TI - Should relatives of patients with colorectal cancer be screened? A critical review of the literature. AB - PURPOSE: The objective of our investigation was to attempt to address the controversial issue concerning index screening and surveillance of relatives of patients with colorectal cancer and to identify those areas of research that should be considered in future studies. METHODS: Relevant literature was reviewed concerning the screening of asymptomatic first-degree relatives of patients with colorectal cancer not associated with the rare autosomal dominant inherited colorectal cancer syndromes. RESULTS: The data reviewed suggest that there is an increased risk of colorectal neoplasia in this population and a significantly higher yield of adenomas and carcinomas when colonoscopy is used for index screening. However, significant variability in study design and screening protocols and inconsistencies in data presentation make clinical interpretation and data analysis confusing and difficult. CONCLUSIONS: There is a critical need for standardization in future studies. Furthermore, as there are no studies that document decreased overall mortality from colorectal cancer in first-degree relatives as a result of screening, the decision as to whether to screen this population needs to be based on future prospective controlled trials. PMID- 7995169 TI - Potential dangers related to transdermal fentanyl (Duragesic) when used for postoperative pain. PMID- 7995170 TI - Therapy of anal fissure using botulin toxin. PMID- 7995171 TI - Folate supplementation and adenomatous colonic polyps. PMID- 7995172 TI - Bone disorders following total gastrectomy. AB - Bone disorders following gastrectomy were studied by measuring absolute and relative bone mineral density of the Wards triangle, serum 1,25-(OH)2-D, alkaline phosphatase, and total serum calcium. The subjects were 20 males who had undergone total gastrectomy not more than three months previously (group A1). Seventeen of these patients were reviewed three years later (group A2). Absolute and relative bone density were significantly lower in group A2 than in A1 (0.52 +/- 0.011 g/cm2 versus 0.6 +/- 0.014 g/cm2, P < 0.01 and 85.5 +/- 1.4% age matched control versus 95 +/- 1.3%, P < 0.01). 1,25-(OH)2-D was significantly lower in group A2 than in group A1 (14.3 +/- 0.97 pg/ml versus 20.6 +/- 1.02 pg/ml, P < 0.01). There was no difference in alkaline phosphatase and calcium serum concentration. The mean weight loss was 6.26 +/- 0.57% over the follow-up period, and weight loss correlated with absolute and relative bone density (r = 0.74, P < 0.01). There was a positive correlation between 1,25-(OH)2-D and absolute or relative bone density (r = 0.67, r = 0.62 and P < 0.01). These data suggest that bone density decrease has already occurred three years after total gastrectomy and is positively correlated to 1,25-(OH)2-D deficiency. As no differences in serum alkaline phosphatase and serum calcium concentration were found, these factors are of little value for the early detection of postgastrectomy bone disorders, whereas weight loss is a valuable screening parameter. PMID- 7995173 TI - In vitro studies of gastric juice in patients with food-cobalamin malabsorption. AB - Food-cobalamin absorption depends on the initial release of cobalamin from its binders in food. Therefore, the characterization of patients' gastric juices and their behavior in this process was undertaken. Pentagastrin-stimulated gastric juice specimens from three patients with severe food-cobalamin malabsorption, six patients with mild malabsorption, and five patients with normal absorption were tested for pH, pepsin, intrinsic factor content, and an in vitro method that quantitates transfer of cobalamin from egg yolk to gastric R binder. Transfer of cobalamin correlated best with in vivo egg yolk-cobalamin absorption test results in the 14 patients (r = 0.731, P < 0.005). Transfer also correlated inversely with gastric juice pH (r = -0.619, P < 0.02). Basal gastric juice specimens, with their higher pH, from the same subjects failed to promote cobalamin transfer until their pH was lowered to 1.0-1.3. Pepsin levels did not correlate with in vitro transfer or with absorption in vivo; nevertheless, raising the low pepsin concentration of one stimulated gastric juice improved transfer, while inhibiting pepsin activity with pepstatin A inhibited transfer. Mixing experiments with selected stimulated gastric juices demonstrated that poor in vitro transfer, which in a few cases seemed unrelated to pH or pepsin levels, was not due to any inhibitory activity of such gastric juices. These studies confirm that gastric acid and pepsin play a central role in releasing food-bound cobalamin and transferring it to R binder, but suggest that other, still unidentified gastric defects occasionally contribute to impaired transfer; the latter defects are not inhibitory in nature but seem to involve the absence of a permissive activity.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7995174 TI - Declined human esophageal mucin secretion in patients with severe reflux esophagitis. AB - It has been recently demonstrated that human esophageal submucosal mucous glands exhibit the ability to secrete copious amounts of mucin, well known within the gastrointestinal tract for its protective quality against hydrogen ion and pepsin. Since mucin may also play a protective role within the esophageal compartment, we have studied the rate of secretion of esophageal mucin in patients with RE. Mucin was assessed by periodic acid-Schiff methodology in esophageal secretion collected during continuous perfusion with saline (period I) followed by HCl (period II), HCl/pepsin (period III), and final saline (period IV), mimicking the natural gastroesophageal scenario. The basal rate of the luminal release of mucin in patients with grade II RE was 18% lower as compared with controls. During exposure of the esophageal mucosa to an HCl/pepsin solution, esophageal mucin output in the RE group was 52% lower than in the control group (0.154 +/- 0.027 vs 0.320 +/- 0.049 mg/cm2/min; P = 0.025). Furthermore, the rates of esophageal mucin output in patients with grade III RE during esophageal perfusion with saline and HCl/pepsin were 62% (0.090 +/- 0.021 vs 0.239 +/- 0.036 mg/cm2/min; P = 0.016) and 86% (0.048 +/- 0.010 vs 0.320 +/- 0.049 mg/cm2/min; P = 0.001) lower when compared with corresponding values in controls. After endoscopic healing of RE, the overall impairment in the rate of esophageal mucin secretion in patients with grade II improved from 31% to 17% at the end of therapy, whereas in patients with grade III the impairment in mucin secretion improved only marginally from 71% to 69%.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7995175 TI - Equine model of inducing ulceration in alimentary squamous epithelial mucosa. AB - Ulceration of the gastric squamous epithelial mucosa was induced in 10 horses using a feeding protocol previously shown to expose the gastric mucosa to repeated periods of high acidity. The feeding protocol consisted of alternating feed deprivation with free access to hay. Over a period of seven days, each horse was provided hay for 84 hr and deprived of hay for 84 hr. Hay was never withheld for longer than 24 hr at a time. Gastroscopy was performed on each horse at the beginning of the protocol after 12 hr of feed deprivation, and after a total of 36 hr, 60 hr, and 84 hr of feed deprivation. All horses had normal esophageal and gastric mucosa at the beginning of the protocol. Alternating periods of feeding and feed deprivation resulted in progressive ulceration of the gastric squamous epithelial mucosa in all but one of the horses. Lesions progressed from erosions to ulceration within 36-72 hr of feed deprivation, and by 84 hr of feed deprivation ulcers had developed thickened, raised margins. Esophageal mucosa appeared normal in all horses throughout the study. The protocol of alternating feeding with feed deprivation in horses consistently produced gastric squamous epithelial ulceration and provided a useful model for characterizing temporal transitions in peptic-injured alimentary squamous epithelia. PMID- 7995176 TI - Influences of urethane anesthesia on indomethacin-induced gastric mucosal lesions in rats. Relation to blood glucose levels. AB - Effects of urethane on gastric motility and mucosal ulcerogenic responses induced by indomethacin were investigated in the rat in relation to blood glucose levels (BGL) and compared with those of pentobarbital Na. Urethane (1.25 g/kg) given intraperitoneally, caused a progressive and significant rise in BGL, while pentobarbital (30 mg/kg) given intraperitoneally did not affect BGL. Subcutaneous administration of indomethacin (25 mg/kg) caused high-amplitude gastric contractions and induced hemorrhagic lesions in the stomachs of conscious rats. These lesions were significantly inhibited by urethane but not pentobarbital. Administration of urethane abolished basal gastric motility and almost completely suppressed the motility responses induced by indomethacin, while pentobarbital did not have much effect on gastric motility under basal and indomethacin stimulated conditions. Acid secretion was significantly decreased by urethane and increased by pentobarbital. Pretreatment of the animals with yohimbine (5 mg/kg, subcutaneously) but not prazosin (0.5 mg/kg) inhibited the elevation in BGL seen after administration of urethane and allowed resumption both gastric motility and ulcerogenic responses induced by indomethacin, with less change in acid secretion. These results suggest that intraperitoneal administration of urethane prevented indomethacin-induced gastric lesions, probably by inhibiting the enhanced gastric motility response, and this effect may relate to its hyperglycemic action mediated by alpha 2-adrenoceptors. These findings also provide further evidence to support the importance of gastric motility in the pathogenesis of these lesions. PMID- 7995177 TI - Capsaicin-sensitive sensory neurons in healing gastric lesions induced by HCl in rats. AB - The role of capsaicin-sensitive sensory neurons in the healing of HCl-induced gastric lesions was investigated in rats. Rats fasted for 18 hr were given 0.6 N HCl orally for induction of gastric lesions, and they were fed normally from 1 hr later. On various days after HCl treatment, area of lesions, acid secretion, mucosal H+ permeability, and blood flow responses were measured. Functional ablation of capsaicin-sensitive sensory neurons was performed two weeks before the experiment by subcutaneous injections of high-dose capsaicin. Sensory deafferentation did not affect the development of gastric damage in response to HCl but significantly delayed the healing of these lesions. The mucosa damaged by HCl secreted less acid but showed significant rise in H+ permeability, resulting in acid back-diffusion accompanied by an increase of mucosal blood flow. Sensory deafferentation had no effect on acid secretion and mucosal permeability changes in the damaged stomach but completely blocked the hyperemic response caused by acid back-diffusion. Capsaicin-sensitive sensory neurons may contribute to healing of gastric lesions, probably by mediating the mucosal hyperemic responses associated with acid back-diffusion and by facilitating acid disposal in the mucosa. PMID- 7995179 TI - Extragastric Dieulafoy's disease as unusual source of intestinal bleeding. Esophageal visible vessel. AB - Dieulafoy's disease is a gastric vascular malformation, which typically causes massive hemorrhage. The lesion is most often found in the proximal stomach, but has also been reported in the esophagus and in the small intestine. Three patients with esophageal Dieulafoy's anomaly and recurrent bleeding are reported. For the first time, transendoscopic Doppler ultrasound was used to identify arterial blood flow from the lesions. The ulcerations were treated by injection of adrenaline. Successful therapy resulted in the disappearance of arterial pulsations and no rebleeding occurred. Doppler-controlled endoscopic intervention should be the first line of treatment in the esophageal vessel stump. PMID- 7995178 TI - Role of myosin light-chain kinase and protein kinase C in pepsinogen secretion from guinea pig gastric chief cells in monolayer culture. AB - We evaluated the role of myosin light-chain kinase (MLCK) and protein kinase C (PKC) in pepsinogen secretion from guinea pig gastric chief cells using a monolayer culture system of chief cells and an enzyme immunoassay system for guinea pig pepsinogen. An MLCK inhibitor, 1-(5-chloronaphthalene-1-sulfonyl)-1H hexahydro-1,4-diazepine (ML-9), significantly inhibited both the basal pepsinogen secretion and the secretion by carbamylcholine chloride (carbachol) or ionomycin without affecting intracellular free Ca2+ concentration ([Ca2+]i), but not by 12 O-tetradecanoylphorbol-13- acetate (TPA) or forskolin. A PKC inhibitor, 1-(5 isoquinolinesulfonyl)-2-methylpiperazine (H-7), significantly reduced the pepsinogen secretion by carbachol or TPA, but not by forskolin or ionomycin, and did not affect the basal secretion and the [Ca2+]i elevated by carbachol or ionomycin. We concluded that: (1) MLCK plays an important role in basal and drug stimulated pepsinogen secretion, (2) MLCK is involved in the Ca(2+)-dependent intracellular pathway but not in the cyclic adenosine monophosphate (cAMP) dependent pathway, (3) PKC is irrelevant to activation of MLCK, and (4) increases in cAMP and [Ca2+]i are independent of activation of PKC. PMID- 7995180 TI - Esophageal inflammatory fibroid polyp. Endoscopic and radiologic features. AB - We present the case of a 60-year-old male patient, who had several episodes of melena during the last years. One month ago he had a new episode of digestive bleeding, and an endoscopic study was performed that showed at 35 cm from the dental arcade a polypoid, pedunculated lesion, with a diameter of 5 cm and a submucosal aspect, a few erosions on its surface and a fibrin deposit. Its head reached the cardia, and it bled when touched by the endoscope. The biopsies taken were negative. X-ray and CT studies confirmed the existence of a mass compatible with a submucosal lesion. The patient was operated and the tumor was excised. The histologic study showed an inflammatory fibroid polyp, an entity very rarely described at the level of the stomach, duodenum, small intestine, and colon and exceptionally described at the esophageal level. PMID- 7995181 TI - Endoscopic and histologic resolution of gastric pseudolymphoma (reactive lymphoid hyperplasia) following treatment with bismuth and oral antibiotics. AB - Gastric pseudolymphoma is a rare disorder of unknown etiology that can undergo transformation into malignant lymphoma. This report describes the first case of a gastric pseudolymphoma associated with Helicobacter pylori infection that underwent complete clinical, endoscopic, and histologic resolution following treatment with bismuth subsalicylate, amoxicillin, and metronidazole. The eradication of Helicobacter pylori may have eliminated ongoing antigenic stimulation that has previously been postulated to be responsible for the development and subsequent progression of gastric pseudolymphoma. PMID- 7995182 TI - Neutrophil-independence of the initiation of colonic injury. Comparison of results from three models of experimental colitis in the rat. AB - Although the role of neutrophils in the pathogenesis of several forms of gastrointestinal injury has been well demonstrated, their role in the development of experimental colonic injury is less clear. To examine whether neutrophils play a role in the development of experimental colitides, the effects of a sustained neutropenia on multiple indices of colonic injury in rats was examined 24 hr following the initiation of colitis with the intrarectal application of acetic acid, trinitrobenzene sulfonic acid (TNBS)-ethanol, or the potent proinflammatory agent, phorbol-12-myristate-13-acetate (PMA). In comparison to animals with normal neutrophil counts and colitis induced by any of the three agents, no attenuation in macroscopic damage or histopathologic injury was observed in neutropenic animals exhibiting a greater than 95% reduction in circulating neutrophils and 85% reduction in tissue-associated myeloperoxidase activity. Although the tissue edema associated with acetic acid or PMA-induced colitis was not reduced by neutropenia, the colonic edema associated with TNBS colitis was attenuated by prior neutrophil depletion with anti-neutrophil antiserum. Despite our initial hypothesis that neutrophils played a key role in the genesis of experimental colitis (especially that induced by PMA), the results demonstrated that these cells are not essential for the development of the major pathological features of colitis induced by this agent, acetic acid, or TNBS. Although these results support the proposal that in these models of colitis, inflammation develops secondary to injury (rather than the converse), further studies will be necessary to elucidate the role of inflammatory cells other than neutrophils in the genesis of experimental colitides. PMID- 7995184 TI - Oral bacteriotherapy for viral gastroenteritis. AB - The effect of orally administered lactobacilli on acute rotavirus diarrhea was tested in 42 well-nourished children ages 5-28 months. After oral rehydration, the patients were randomized to a study group, receiving human Lactobacillus casei strain GG 10(10) colony-forming units twice daily for five days, or a control group not given lactobacilli. Lactobacillus GG was found in the feces in 83% of the study group. The diarrheal phase was shortened in that group. Dietary supplementation with lactobacilli significantly influenced the bacterial enzyme profile: urease activity during diarrhea transiently increased in the control group but not in the study group; F = 8.6, P = 0.01. No intergroup differences were found in beta-glucuronidase, beta-glucosidase, and glycocholic acid hydrolase levels. We suggest that rotavirus infection gives rise to biphasic diarrhea, the first phase being an osmotic diarrhea and the second associated with overgrowth of specifically urease-producing bacteria. Oral bacteriotherapy appears a promising means to counteract the disturbed microbial balance. PMID- 7995183 TI - Effects of new fish oil derivative on fatty acid phospholipid-membrane pattern in a group of Crohn's disease patients. AB - Fish oil has been recently proposed as a possible effective treatment in inflammatory bowel disease (IBD); however, a lot of annoying side effects (ie, belching, halitosis, diarrhea, etc) affect patient compliance. We carried out a study of patient tolerance in a group of Crohn's disease (CD) patients with a new fish oil derivative consisting of 500-mg capsules of eicosapentaenoic docosahexaenoic (EPA 40%-DHA 20%), a free fatty acid mixture (Purepa), and we also evaluated its incorporation into phospholipids, both in plasma and in red cell membranes. Five groups of 10 CD patients in remission received nine Purepa capsules daily in four different preparations (A: uncoated, B: coated, pH 5.5; C: coated, pH 5.5, 60 min time release; D: coated, pH 6.9) and 12 x 1-g capsules daily of a triglyceride preparation (Max-EPA, EPA 18%-DHA 10%), respectively. We coated three of the four Purepa preparations in order to delay the release of contents in an attempt to minimize the side effects. After six weeks of treatment, the group taking Purepa capsules, coated, pH 5.5, 60 min time release (group C) showed the best incorporation of EPA and DHA in red blood cell phospholipid membranes (EPA from 0.2 to 4.4%, DHA from 3.7 to 6.3%), and no side effects were registered, whereas in all other groups side effects were experienced in 50% or more of subjects. This new preparation will make it possible to treat patients for long periods. PMID- 7995186 TI - Does the menstrual cycle affect anorectal physiology? AB - It has been shown that during the luteal phase of the menstrual cycle women excrete hard stools and have delayed transit, while at the time of menses, stools are looser and more frequent. The relationship between the menstrual cycle and anorectal physiology, and whether the timing of manometry testing should be standardized within the menstrual cycle has not been previously investigated. In this study, the anorectal responses to balloon distension during days 1-4 (menses), 8-10 (follicular phase), 18-20 (luteal phase) and 24-28 (premenstrual) of the menstrual cycle in 20 healthy female volunteers (ages 18-39 years) was measured. Stools were significantly looser during menses [2.32 (2.1-2.5); mean (95% CI)] compared with the luteal phase [1.98 (1.8-2.2): F(3,30) = 3.1; P < 0.04). However, there were no changes in rectal sensitivity, distension-induced rectal motility, rectal compliance, or the volumes required to induce the initial and sustained internal aral sphincter relaxations. In conclusion, although stools become looser at the time of menses, anorectal responses to balloon distension are unaltered. This suggests that the changes in bowel habit associated with the menstrual cycle are unrelated to changes in anorectal physiology. Furthermore, routine manometric testing can be performed at any time during the menstrual cycle without fear of conflicting results. PMID- 7995185 TI - Amino acid derivatives of 5-ASA as novel prodrugs for intestinal drug delivery. AB - In an attempt to obtain site-specific delivery of 5-ASA in the intestinal tract, we have determined the extent of absorption and metabolism of a number of novel 5 ASA derivatives, namely, (N-L-glutamyl)-amino-2-salicylic acid (1), (N-L aspartyl)-amino-2-salicylic-acid (2), 5-aminosalicyl-L-proline-L-leucine (3), and 5-(N-L-glutamyl)-aminosalicyl-L-proline-L-leucine (4), which are selectively cleaved by intestinal brush border aminopeptidase A and carboxypeptidases. These novel prodrugs, 5-ASA, and sulfasalazine were administered to adult Fisher rats (N = 30) and to animals that had undergone prior colostomy (N = 30). Urine and feces were collected at timed intervals for 48 hr and the metabolites, 5-ASA, and N-acetyl-5-ASA were measured by high-performance liquid chromatography. The absorption and metabolism of all compounds were essentially identical in colostomized and normal animals. 5-ASA exhibited a rapid proximal intestinal absorption as evidenced by the high cumulative urinary excretion (> 65%) and low fecal excretion. Sulfasalazine, as expected, exhibited a lower urinary recovery (< 35%) and higher fecal excretion of 5-ASA and its metabolite. The novel glutamate and aspartate derivatives (1 and 2) behaved similarly to sulfasalazine, while administration of the proline-leucine derivative (3) resulted in urinary and fecal recovery values intermediate with respect to those observed with 5-ASA and sulfasalazine. 5-(N-L-Glutamyl)-aminosalicyl-L-proline-L-leucine yielded the highest fecal recovery of 5-ASA and its N-acetyl derivative, indicating a more efficient delivery to the distal bowel. Amino acid derivatives of 5-ASA appear to be potentially useful prodrugs for the site-specific delivery of 5-ASA to different regions of the intestinal tract. PMID- 7995187 TI - Loperamide improves anal sphincter function and continence after restorative proctocolectomy. AB - The physiological and clinical effects of loperamide treatment versus placebo were investigated in a randomized, double-blind, crossover study in patients operated with restorative proctocolectomy. Sixteen patients operated with endoanal mucosectomy and a handsewn ileal pouch-anal anastomosis and 14 patients operated with abdominal proctocolectomy and stapling of the pouch to the top of the anal canal were studied. While loperamide treatment increased resting anal pressure in both groups of patients by approximately 20% (P < 0.05), squeeze pressure was not affected. Loperamide did not affect pouch volume or contractility. Sensory thresholds and the recto/pouch-anal inhibitory reflex were not influenced by loperamide treatment. Clinical function was improved, with a reduced bowel frequency and an improved nighttime continence, with less soiling (P < 0.05) as well as need to wear a protective pad. PMID- 7995188 TI - Motility of isolated bowel segment Iowa model III. AB - The isolated bowel segment (IBS) is an amesenteric segment of bowel that is devoid of extrinsic nerves and yet is viable with motility and absorption preserved after its mesentery is completely severed. The IBS is created by initial coaptation of a loop of bowel to a host organ, such as muscle (Iowa model I), liver (Iowa model II), or intestine, and secondary severance of its mesentery several weeks later. In previous studies using Iowa models I and II, the viability, motility, and absorption of the IBS were preserved by vascular collaterals, which form across the coaptation. In rats, an IBS was created in the jejunum by initial enteroenteropexy (Iowa model III), followed by its mesenteric division five weeks later. At the second laparotomy, bipolar electrodes were implanted in the IBS and the adjacent jejunum. One week later, myoelectrical recording was performed during a fasting state. Coordinated abroad propagation of migrating motor complex (MMC) was observed in the IBS. The MMC period was 16.9 +/ 1.7 and 19.3 +/- 0.8 min in the intact bowel, and 22.8 +/- 0.8 min in the IBS (P = 0.1). After feeding, the MMC in the IBS was replaced by irregular spike burst activity similar to that observed in the intact bowel. This study concludes that the IBS Iowa model III can be used for studies of bowel physiology. PMID- 7995189 TI - Noninvasive evaluation of kinetics of gallbladder emptying and filling in the dog. A real-time ultrasonographic study. AB - Patterns of gallbladder contraction induced by a meal or cerulein were examined by means of real-time ultrasonography in conscious dogs. The postprandial gallbladder emptying was characterized by two parameters of the power-exponential function: the gallbladder half emptying time T1/2 = 47.3 +/- 4.7 min and the curve shape parameter S = 0.866 +/- 0.036. Cerulein infused at stepwise increasing rates of 0.7, 2.2, 7.4, 22.2, and 66.5 pmol/kg/hr, administered each for 10 min, evoked a gallbladder contraction to 87.4 +/- 3.8%, 66.7 +/- 2.4%, 44.5 +/- 1.5%, 25.9 +/- 2.1%, and 11.9 +/- 2.0% of the basal volume, respectively. The dependence of the gallbladder emptying on the dose of cerulein was described by the equation of linear regression y - 21.33 [ln(dose + 1)] + 95.81 (r = -0.963, P < 0.001). Accordingly, the cerulein dose required to evoke a 50% reduction of the gallbladder volume amounted to 7.6 pmol/kg/hr (95% confidence interval: 6.8-8.6 pmol/kg/hr). A plateau at the level of about 44% of the basal gallbladder volume characterized the time-course of the gallbladder emptying between 20 and 60 min of the infusion at a constant rate of 7.4 pmol/kg/hr. On the other hand, the 1-hr infusion of 22.2 pmol/kg/hr evoked a continuous decrease in the gallbladder volume with a nadir of 10.2 +/- 0.7% achieved at 60 min. Refilling of the gallbladder, contracted after a 1-hr infusion of cerulein, was complete within 30 and 60 min after the end of infusion for rates of 7.4 pmol/kg/hr and 22.2 pmol/kg/hr, respectively. The time course of the gallbladder filling after cessation of 1-hr infusion of cerulein at 7.4 pmol/kg/hr was described by the equation of linear regression of relative gallbladder volumes vs time: y = 1.732x + 48.61 (r = 0.739, P < 0.001). Refilling of the gallbladder was faster during the first 30 min (y = 2.191x + 7.13, r = 0.885, P < 0.001) and slower between 30 and 60 min (y = 1.218x + 74.97, r = 0.533, P < 0.001) after the end of a 1-hr infusion of cerulein at a rate of 22.2 pmol/kg/hr. PMID- 7995190 TI - Impact of microcirculatory flow pattern changes on the development of acute edematous and necrotizing pancreatitis in rabbit pancreas. AB - Impairment of pancreatic microcirculation has often been advocated as one pathogenic mechanism in necrotizing pancreatitis. In contrast, data on pancreatic capillary perfusion in edematous pancreatitis are scarce. It was the aim of this experimental study to compare changes in pancreatic microcirculation in edematous and necrotizing pancreatitis. Twelve rabbits were allocated to two groups. Two different models of acute pancreatitis were used. Edematous pancreatitis was elicited by intravenous administration of cerulein (25 micrograms/kg/hr) (N = 6). Necrotizing pancreatitis of the biliary type was induced by pressure-controlled intraductal infusion of a mixture of taurocholate, trypsin, and blood (N = 6). Pancreatic microcirculation was quantified by means of intravital microscopy assessing functional capillary density, blood cell velocity, and distribution of the plasma marker FITC-dextran 70. Systemic hemodynamics were maintained at baseline values by fluid administration. Regardless of edema or necrosis, pronounced extravasation of FITC-dextran was recorded in the early stage of pancreatitis. In cerulein-induced pancreatitis, hyperemia developed as indicated by an increase in blood cell velocity in the presence of homogeneous capillary perfusion. In contrast, a progressive reduction of the number of perfused capillaries was detected in necrotizing pancreatitis. In conclusion, pancreatic microvascular perfusion may be regarded as an important pathogenetic factor for the determination of acute pancreatitis. PMID- 7995191 TI - Hepatitis delta virus RNA in serum of patients with chronic delta hepatitis. AB - We studied 28 patients with chronic delta hepatitis for the presence of hepatitis delta virus (HDV) RNA in serum. The hot start polymerase chain reaction (PCR) method, in which the reaction begins at 60-80 degrees C, showed a higher sensitivity than conventional PCR reaction. Additionally, the presence of hepatitis B (HBV) and C virus (HCV) infections were determined by PCR. HDV RNA was detected in 26 patients (93%), HBV DNA in 22 (79%), and HCV RNA in only one. Detection of HDV RNA correlated very well with detection of hepatitis delta antigen by immunostaining in the liver. In six patients HDV RNA was detectable despite the absence of HBV DNA in serum, suggesting that high levels of HBV are not required for HDV replication. Of 29 control patients with chronic hepatitis B without antibody to HDV, none had detectable HDV RNA, while all had HBV DNA in serum. Detection of HDV RNA with PCR proved highly sensitive and specific, demonstrating that virtually all patients with chronic HDV infection had ongoing viral replication. PMID- 7995192 TI - Increased serum iron and iron saturation without liver iron accumulation distinguish chronic hepatitis C from other chronic liver diseases. AB - One hundred twenty-three patients with chronic liver diseases of various etiologies were evaluated for their iron status. The patients were divided into four distinct groups: chronic hepatitis C (63), chronic hepatitis B (14), B + C (3) and nonviral chronic liver diseases (43). In 107 patients (87%) the chronic liver disease was confirmed by biopsy. Mean serum iron (+/- SD) levels in the above four groups were: 166 +/- 62, 103 +/- 52, 142 +/- 48, and 115 micrograms/dl; iron-binding capacity was 346 +/- 80, 325 +/- 72, 297 +/- 27, and 374 +/- 75 micrograms/dl, and iron saturation 50 +/- 18, 32 +/- 16, 48 +/- 16, and 28 +/- 10%, respectively. Serum ferritin, increased in all four groups, was highest in HCV; however, no evidence of hepatic iron accumulation could be found in any of the patients. There were no significant differences in liver function parameters measured in the four groups. We conclude that serum iron, iron saturation, and ferritin are increased in patients with hepatitis C in comparison to hepatitis B or other nonviral, nonhemochromatotic liver diseases. The increased iron status in hepatitis C patients is not manifested by increased liver iron. Awareness of these distinct features of chronic hepatitis C is essential in the diagnosis and treatment of chronic liver diseases. PMID- 7995193 TI - Clinical and histologic predictors of response to interferon-alpha in patients with chronic hepatitis C viral infection. AB - To evaluate if any pretreatment characteristics of patients with chronic hepatitis C (HCV) can be used to predict response to the current recommended dose (3 million units three times a week) and higher doses of interferon-alpha (IFN), we retrospectively assessed the response of 37 patients with HCV who were treated with IFN. Sixteen patients (43%) responded to the standard dose of IFN with normalization of ALT. Weight and liver histology were found to be significant factors for response. The responders weighed significantly less than nonresponders (161.8 +/- 35.5 lb versus 200.3 +/- 45.4 lb, P = 0.008). Seventy five percent of patients with chronic lobular or persistent hepatitis were responders, whereas only 28% of patients with more advanced hepatitis responded (P = 0.01). There was no correlation between the degree of bile duct damage or steatosis and response rate. This study suggests that obesity and severe histologic injury are negative predictive factors of response to the current recommended dose of IFN. The adequacy of the current recommended dose of IFN in overweight patients needs to be investigated. PMID- 7995194 TI - Clinical significance of plasma endothelin-1 in patients with chronic liver disease. AB - To determine the clinical significance of plasma endothelin-1 in chronic liver disease, these levels were measured by radioimmunoassay. The plasma endothelin-1 levels in patients with cirrhosis (N = 16) (2.04 +/- 0.25 pg/ml) and patients with hepatocellular carcinoma (N = 22) (2.23 +/- 0.17 pg/ml) increased significantly compared with controls (N = 16) (1.17 +/- 0.17 pg/ml) and patients with chronic hepatitis (N = 11) (1.09 +/- 0.19 pg/ml) (P < 0.01). The presence of ascites rather than tumor volume was associated with a significant elevation of endothelin-1. Endothelin-1 showed significant negative correlations with parameters of hepatic function, including indocyanine green clearance, serum albumin, and prothrombin time. Although endothelin-1 was not correlated with plasma renin activity and plasma endotoxin, it demonstrated a significant positive correlation with the plasma level of atrial natriuretic peptide (r = 0.42, P < 0.01). These findings demonstrate that plasma endothelin-1 increased in proportion to the severity of liver damage and may be causally related with the derangement of systemic/renal hemodynamics and fluid and electrolyte homeostasis seen in advanced liver disease. PMID- 7995195 TI - Systemic treatment with recombinant human epidermal growth factor accelerates healing of sclerotherapy-induced esophageal ulcers and prevents esophageal stricture formations in pigs. AB - Human epidermal growth factor (EGF), a small polypeptide (6 kDa) with mitogenic properties, has been implicated in the protection of gastrointestinal mucosal integrity. The efficacy of EGF in the prevention and healing of sclerotherapy induced esophageal lesions was investigated in 24 minipigs with surgically induced portal hypertension. In addition, the effect of EGF on intragastric acidity and pharmacokinetics was investigated as possible means to explain its protective mechanism of action. The animals underwent three weekly sessions of sclerotherapy with polidocanol 2% and were concomitantly and for an additional three weeks treated with either placebo or EGF administered paravenously in the esophagus and/or subcutaneously. The subcutaneous treatment with EGF significantly (P < 0.05) reduced esophageal stricture and scar formations associated with sclerotherapy. Gastric pH values were significantly (P < 0.01) elevated only in animals receiving subcutaneous injections of EGF. Furthermore, the subcutaneous administration of EGF was associated with unexpected prolonged plasma concentration of the peptide. These results suggest a possible clinical value of EGF as an adjunctive treatment with the sclerotherapy. PMID- 7995196 TI - "Pseudo-pseudotumor" of the liver. Adenocarcinoma presenting as an inflammatory pseudotumor. PMID- 7995198 TI - Frontiers in gastric emptying. Proceedings of an international symposium. Lausanne, Switzerland, September 26-28, 1993. PMID- 7995199 TI - Measurement of gastric emptying and gastric motility by magnetic resonance imaging (MRI). AB - Hitherto it has been impossible to measure noninvasively gastric emptying and motility from multiple regions of the stomach in humans. We describe the development of a novel methodology to achieve this using magnetic resonance imaging (MRI). Initial validation studies performed in five healthy volunteers demonstrated similar gastric emptying curves and secretion rates after ingestion of 10% dextrose labeled with [Gd]DOTA, assessed by MRI ([Gd]DOTA as meal marker) and a simultaneous double-indicator technique. Comparison between MRI and scintigraphy in five patients also gave similar results. Application of newer MRI technology allowing a series of coronal scans 1.2 sec apart permitted quantification of wall motion in the proximal and distal stomach in seven healthy volunteers. These results indicate that MRI provides new insights into the mechanisms responsible for both normal and disordered emptying. PMID- 7995197 TI - Steroid hormone receptors in three human gastric cancer cell lines. AB - Steroid hormone receptors in three human gastric adenocarcinoma cell lines and their transplanted tumors (except nontumorigenic KATO-III) in nude mice were determined by dextran-coated charcoal assay. Progesterone receptors (PgR) were found in all cell lines, transplanted NUGC-3, and AZ 521 tumors. Estrogen receptors (ER) were found in KATO-III cells, transplanted NUGC-3, and AZ 521 tumors, whereas glucocorticoid receptors (GR) were found only in NUGC-3 tumor and no androgen receptor was found in any cell lines or transplanted tumors. Since NUGC-3 cells had ER, PgR, and GR, it was used for the study of the effects of steroid hormones on growth. The results showed the cell cycle phase distributions and growth rate of transplanted tumors were similar in hormone-treated and nontreated groups. The persistent expression of PgR in gastric cancer cell lines and tumors, and the slight increase of tumor volumes in the progesterone-treated group suggests that progesterone and its receptors may be important in the pathogenesis of gastric cancer, but their biological function remains to be elucidated. PMID- 7995201 TI - Gastric emptying of liquid meals measured noninvasively in humans with [13C]acetate breath test. AB - The aim of the present study was to develop a breath test to measure liquid gastric emptying rates that would be without radiation exposure and applicable to field testing. Four different test meals were investigated: a glucose meal, an amino acid meal, a fat meal, and a mixed meal (Ensure). The test meals were labeled with two markers, [13C]acetate and PEG-4000 (polyethylene glycol 4000). Gastric emptying rates were measured simultaneously by both breath test and the double-indicator technique in eight healthy male subjects. The appearance of 13CO2 in the breath closely reflected gastric emptying of the four test meals as measured by the double-indicator technique. It is concluded that the [13C]acetate breath test is a reliable, noninvasive test to measure gastric emptying rates of liquid test meals. PMID- 7995200 TI - [*C]octanoic acid breath test to measure gastric emptying rate of solids. AB - We have developed a breath test to measure solid gastric emptying using a standardized scrambled egg test meal (250 kcal) labeled with [14C]octanoic acid or [13C]octanoic acid. In vitro incubation studies showed that octanoic acid is a reliable marker of the solid phase. The breath test was validated in 36 subjects by simultaneous radioscintigraphic and breath test measurements. Nine healthy volunteers were studied after intravenous administration of 200 mg erythromycin and peroral administration of 30 mg propantheline, respectively. Erythromycin significantly enhanced gastric emptying, while propantheline significantly reduced gastric emptying rates. We conclude that the [*C]octanoic breath test is a promising and reliable test for measuring the gastric emptying rate of solids. PMID- 7995202 TI - Role of electrogastrography and gastric impedance measurements in evaluation of gastric emptying and motility. AB - Electrogastrography records electrical potential variations brought about by myoelectrical activity of the stomach. Abnormal myoelectrical rhythms such as tachygastrias may also be detected. Electrogastrography provides little information on gastric motility and emptying. Impedance epigastrography is a technique that uses changes in epigastric impedance to evaluate gastric emptying of large-volume liquid meals. The results are inferior to those of tomographic impedance imaging. Phasic antral contractions may lead to phasic impedance changes recorded with nonimaging techniques and a phasic signal recorded with high-speed electrical impedance tomography. However, the relationship between phasic contractions and phasic variations in impedance do not appear consistent enough to allow clinical application of the technique. PMID- 7995203 TI - Role and integration of mechanisms controlling gastric emptying. Frontiers in gastric emptying. PMID- 7995204 TI - Feedback regulation and sensation. Frontiers in gastric emptying. PMID- 7995205 TI - Mediation, muscle receptors, neurotransmitters, and drugs. Frontiers in gastric emptying. PMID- 7995206 TI - Methods to study gastric emptying. Frontiers in gastric emptying. PMID- 7995208 TI - Control of gastric emptying by gastric tone. AB - During ingestion of food, the stomach relaxes to accommodate the meal and, subsequently, a progressive gastric contraction parallels gastric emptying. Intestinal nutrients trigger feedback relaxatory mechanisms that regulate gastric tone and, hence, the nutrient load delivered into the small intestine. This regulation of gastric tone is mediated, at least in part, via the vagus. Defective gastric tone is associated with impaired gastric emptying, as seen in patients with postsurgical gastroparesis. However, increased intragastric pressure, corresponding with defective gastric accommodation, induces abdominal symptoms, but does not alter the gastric emptying pattern. These data indicate that gastric emptying is controlled by complementary mechanisms: gastric tone exerts an emptying force, but gastric outlet resistance is also an important regulator. PMID- 7995207 TI - Axial forces during gastric emptying in health and models of disease. AB - The propulsive forces involved in gastric emptying of solid and liquid chyme are incompletely characterized, and the contribution of the proximal region of the stomach to overall propulsion has not been quantifiable. We have used an axial force catheter to characterize longitudinally directed forces during gastric emptying in man. The topography of these forces has been described relative to circumferential contractions, and the contribution of axial forces in experimental models of dumping and gastric stasis were quantified by assessing the effects of intravenous erythromycin and intraduodenal lipid, respectively. There is an excellent correlation between axial forces and gastric emptying of solids in health and in models of gastric dysmotility, suggesting that the axial force catheter semiquantitatively measures propulsive forces during emptying of the human stomach. PMID- 7995209 TI - Gastric motility measurement by MRI. AB - The motor mechanisms associated with gastric emptying of nutrient liquids are unclear. Gastric emptying and motility were determined in seven healthy volunteers using an MRI technique following ingestion of 500 ml of (1) 10% and (2) 25% dextrose labeled with 1 mM Gd-DOTA. Emptying was determined with transaxial scans and motility during fast coronal scans 1.2 sec apart. Emptying was slower after ingestion of 25% dextrose. Following both meals, proximal gastric diameter remained relatively constant, while antral contractile frequency and depth varied markedly. These variations were greater after 10% dextrose. These studies suggest that antral motility changes contribute to slowing of gastric emptying by nutrient meals. PMID- 7995210 TI - Vagal control of transpyloric flow and pyloric resistance. AB - Vagal control of pyloric resistance was evaluated in anesthetised pigs by recording gastropyloroduodenal motility and transpyloric flow during emptying of a liquid nonnutrient meal. Vagotomy did not modify pyloric resistance or the characteristics of the flow pulses. Electrical stimulation of the distal stumps of cervical or thoracic vagus nerves decreased pyloric resistance and triggered flow pulses of large stroke volume. This was associated with increased fundic tone and pressurization of the antrum. Phentolamine but not propranolol reduced the responses to vagal stimulation. These observations demonstrate that reduced pyloric resistance is one mechanism by which vagal activation promotes transpyloric flow. PMID- 7995211 TI - Modulation of pumping function of gastric body and antropyloric contractions. AB - Gastric and antropyloric phasic contractions control transpyloric pulsatile flow, the major mechanism of gastric emptying. Both the occurrence and patterning of phasic gastric contractions are highly modulated by intestinal feedback mechanisms, with resultant variation in gastric emptying. The observed patterns of these contractions can only be plausibly explained by the action of neural influences on gastric motility. These influences derive from several mechanisms driven by intestinal feedback, central nervous system controls, and higher centers, with transmission of signals via intrinsic enteric pathways and extrinsic nerves. It is suggested that the occurrence and patterning of gastric phasic contractions depend on the spatial specificity and local modulation of the intensity of neural stimulation of gastric muscle. The resultant strength of contraction determines the occurrence and timing of lumen occlusion relative to adjacent regions. The timing of lumen occlusion in adjacent regions may be the major determinant of mechanical outcome. PMID- 7995212 TI - Feedback regulation and sensation. AB - The gut is a long tube; food goes down it and across it. Its purpose is to process the food that is consumed in order to optimize absorption of nutrients. It works rather like the reverse of an assembly line in a manufacturing plant with different regions of the gastrointestinal tube specialized sequentially for storage, acid digestion, alkaline digestion, absorption, fermentation, and disposal of waste products. Like an assembly line, it will only work efficiently if the delivery of material to the next process in coordinated closely with the optimum rate of that process. In the gut, the delivery of material is achieved by the propulsive activity of the gastrointestinal smooth muscle, which is in turn programmed by the enteric nervous system and orchestrated by neurohumoral responses to the content of the digesta. It is a finely tuned system; any disturbance can impair absorption and give rise to abdominal discomfort. The stomach is a key organ in the "gastrointestinal dissembly line," It not only commences the digestive process under highly acidic conditions, it stores the masticated food as in a hopper, delivering the acidic digesta or chyme into the duodenum at a rate that is commensurate with the rate at which it can be digested and the products of digestion can be absorbed. The rate at which material enters the small intestine is crucial to achieving optimum nutrition; too fast, and it overwhelms the functional capacity of the small intestine, causing malabsorption and diarrhoea; too slow, and it inhibits the consumption of another meal. The gastrointestinal tract can normally process three medium-sized meals a day. PMID- 7995213 TI - Gastroduodenal sensory mechanisms and CCK in inhibition of gastric emptying in response to a meal. AB - The ability of nutrients in the intestinal lumen to exert feedback control over the proximal gastrointestinal tract function is well recognized, yet the control mechanisms are poorly defined. There is evidence that extrinsic sensory pathways from the intestine are required to initiate this regulatory process. Furthermore, CCK appears to be involved in the gastric response to several intestinal stimuli, such as fat, carbohydrate and protein. Our hypothesis is that nutrients release CCK from the intestine, which then stimulates intestinal mucosal afferents to signal reflex changes in gastric motor function and thus inhibit gastric emptying. PMID- 7995214 TI - Role of 5-hydroxytryptamine in gastrointestinal chemosensitivity. AB - The present electrophysiological investigation examines the effect of 5 hydroxytryptamine (5-HT) on gastrointestinal afferent fiber discharge. 5-HT markedly and specifically stimulated vagal mucosal chemosensitive afferents. The response was mediated by 5-HT3 receptors as demonstrated by the action of 2 methyl-5-HT and antagonism by granisetron. At doses of granisetron that completely block the response to 5-HT, the afferent fibers still responded to both mechanical and chemical stimulation of the mucosa. This sensitivity of extrinsic afferents is in marked contrast to that reported for intrinsic afferents, suggesting fundamental differences in the organization of enteric and vagal reflexes. PMID- 7995215 TI - Modulation of gastric perception and motility in man. Current concepts and correlation with symptoms. AB - Gastric function is controlled by central and peripheral modulation. Most often, afferent information from the stomach does not reach conscious level. At extremes of chemical and mechanical stimulation, however, afferent signals are perceived as pain. Whether or not a signal is perceived depends on gating of afferent signals at the levels of both spinal cord and brainstem. Inhibition of gastric tone and peristalsis during perceived discomfort largely results from stimulation via sympathetic neural pathways. These findings may be clinically relevant because upper gastrointestinal symptoms in many dyspeptic patients could be the result of primary afferent neuron dysfunction rather than motor dysfunction. PMID- 7995216 TI - Conscious perception of gut activity. AB - Regional disturbances of motility in the gastrointestinal tract have been proposed as likely pathogenetic mechanisms for a number of functional gut diseases. However, not all patients with functional gut symptoms exhibit detectable dysmotility. Some investigators have therefore postulated that visceral hypersensitivity to regional luminal stimuli underlies symptoms. The results of emerging research suggest that a pathogenic role of visceral hypersensitivity in functional gut disorders is plausible but that the issue is extremely complex, in view of the interactions between neural control of gut motility, conscious perception of gut signals, and modulation at spinal and brain centers. PMID- 7995217 TI - Abnormal intestinal feedback in disorders of gastric emptying. AB - Many patients who complain of postprandial bloating discomfort and episodic nausea and vomiting exhibit abnormally slow gastric emptying of a standard meal during scintigraphic study. Nevertheless, on clinical grounds, the group of slow emptiers would appear to be comprised of two types of patients: (1) those with primary motor dysfunction (pump failure) and (2) those who have normal muscle performance but abnormally intense inhibition of gastric emptying by nutrients in small intestine (too much feedback). Our studies suggest that these two groups may be distinguished by varying the nutrient content in the test meal during multiple studies of gastric emptying. PMID- 7995218 TI - Mediators and enteric nerve pathways controlling gastric emptying. PMID- 7995219 TI - Excitation-contraction coupling in gastric muscles. AB - Several mechanisms contribute to the regulation of force generated by gastric muscles. Phasic contractions in the stomach are triggered by the propagation of electrical slow waves. These events are associated with an influx of Ca2+ and an increase in intracellular Ca2+ sufficient to elicit contraction. Entry of Ca2+ may be supplemented by the release of Ca2+ from intracellular stores. Excitatory agonists enhance the amplitude of slow waves, increase the amplitude of Ca2+ transients, and increase the force of phasic contractions. Inhibitory agonists have opposite effects. Excitatory agonists may also enhance release of Ca2+ from stores via the production of IP3. Excitatory and inhibitory agonists may also regulate the sensitivity of the contractile apparatus for Ca2+ and therefore alter the contractile response to a given change in intracellular Ca2+. PMID- 7995221 TI - Role of NO in pyloric, antral, and duodenal motility and its interaction with other inhibitory mediators. AB - The antroduodenal region represents a crucial mechanism for the regulation of gastric emptying and prevention of duodenogastric reflux. The pylorus is characterized by a cholinergic excitation from the duodenum to the pylorus and by a potent nonadrenergic noncholinergic (NANC) inhibitory innervation, which can be activated by antral field stimulation and by extrinsic vagal stimulation. The inhibitory effect of both vagal stimulation and antral field stimulation can be abolished in vivo by inhibitors of the L-arginine-NO pathway (L-NAME). During complete blockade of nitric oxide (NO) synthesis in vivo, the contractile response to intraarterial acetylcholine is enhanced and the direct inhibitory effect of vasoactive intestinal peptide (VIP) is still present. Basal or vagally stimulated VIP release was not influenced by L-NAME. NO is a NANC inhibitory transmitter in the pylorus that exerts a tonic inhibition in the pyloric region in vivo. PMID- 7995220 TI - Role and integration of mechanisms controlling gastric emptying. PMID- 7995222 TI - Motilin receptor: a model for development of prokinetics. AB - Erythromycin and related macrolides act as smooth muscle and neural receptors to contract rabbit duodenum and induce phase III migrating motor complex (MMC) activity in intact dogs. A recently developed motilin antagonist confirms that motility effects of erythromycin are mediated by motilin receptors. Despite species, organ, and tissue heterogeneity of motilin receptors, binding experiments with rodent antral smooth muscle tissue provide a good model for the development of this new class of prokinetics. PMID- 7995223 TI - Nitric oxide and gastric relaxation. AB - Pentagastrin enhanced the volume increase caused by isobaric gastric distension in conscious dogs. This effect could be abolished by inhibitors of acid secretion and mimicked by histamine. The increased compliance after pentagastrin was not affected by L-nitroarginine (L-NNA), a blocker of nitric oxide (NO) synthase. L NNA itself reduced the volume increases caused by isobaric gastric distension. Intralipid administration into the duodenum led to a gastric relaxation sensitive to inhibition by L-NNA. The inhibitory effect of L-NNA was partially reversed by L-arginine. Pentagastrin induces a gastric relaxation via a mechanism that involves gastric secretion but not nitric oxide, whereas intraduodenal intralipid induces a gastric relaxation via a NO-dependent mechanism. PMID- 7995224 TI - Neurochemical basis of reflex relaxation in gastric corpus. AB - Three general propositions are set forth: (1) that different test meals delay gastric emptying by different mechanisms, so mixed meals of differing composition are likely to influence gastric emptying by characteristic constellations of mechanisms; (2) that a particular nutrient can delay gastric emptying by more than one pathway; and (3) that a given pathway can use more than one neurotransmitter. The progress made in recent years suggests that it should now be possible to characterize the chemical mediators activated by different nutrients to delay gastric emptying. PMID- 7995226 TI - Gastric motility and emptying studies with radionuclides in research and clinical settings. AB - Scintigraphy remains the most reliable method to measure gastric emptying. Standardized dual-isotope radionuclide gastric emptying techniques and appropriate meals, which stimulate small bowel receptors and utilize correction factors for technical errors, are widely available for research purposes. It is now necessary to apply the same standardized techniques in clinical settings to make the test diagnostically worthwhile. It is possible to quantify gastric motor function scintigraphically and to apply this methodology to study the pathophysiology of gastric emptying in various motor disorders. Ambulatory gastric emptying methods with intraluminal gamma counting probes are currently under development. PMID- 7995225 TI - Methods to study gastric emptying. PMID- 7995227 TI - Volume measurements of gastric antrum by 3-D ultrasonography and flow measurements through the pylorus by duplex technique. AB - We present a method for estimating volumes of abdominal organs using 3-D ultrasonography. In vitro validation experiments demonstrated excellent agreement between estimated and true volumes. In vivo estimations after ingestion of 500 ml meat soup showed greater antral filling and poorer emptying of the gallbladder in patients with functional dyspepsia (FD) than in healthy controls. Abnormal antral filling was associated with dyspeptic symptoms. The relationship between motility and transpyloric movements of luminal contents after ingestion of 500 ml meat soup was studied in healthy subjects by duplex technique. Accurate timing of antegrade and retrograde flow were recorded using bidirectional velocity curves. Mid-cycle and end-cycle reflux were often observed; end-cycle reflux was more frequent in conjunction with coordinated than with uncoordinated antroduodenal contractions. The peristaltic closure of the pylorus was normally preceded by a short gush of duodenogastric reflux. PMID- 7995228 TI - Prominent ophthalmologists who suffered from acute glaucoma. AB - We know of at least four ophthalmologists who suffered from glaucoma had to be treated. I would like to discuss them according to degree of severity of the disease. The first ophthalmologist was hardly bothered at all whereas the fourth one became blind in both eyes. PMID- 7995229 TI - Vision and cognition in the natural philosophy of Albert the Great (Albertus Magnus). AB - Albert the Great (Albertus Magnus, ca. 1197-1280) descended from a nobleman's family in Upper Suebia and studied natural philosophy and theology at the University of Padova, where he joined the Dominican order. Confronted with Aristotelian thought mainly in its Arabic modification (Avicenna, Al-Farabi, Averroes, Alhazen, Costa ben Luca and others) from his days in Padova, he elaborated in several books on the principles of natural philosophy, biology, brain and sense functions and psychology in addition to his theological and exegetic works. His observations and concepts on vision are discussed in detail. It is pointed out that Albert discovered some phenomena of vision not before known such as vestibular nystagmus and rod monochromacy, i.e. total colour blindness accompanied by photophobia. Based on clinical observations Albert also postulated a decussation of the optic nerve fibres at the optic chiasm. Albert's concept of higher order cognitive function is discussed and some of his explanations of dreams and neuropsychiatric disease on the basis of his cognitive model are mentioned. Albert's thoughts on vision and other sense perceptions, higher brain functions and cognition are considered as progressive elaborations of Galenic concepts as adapted by some Patristic theologians and the Arabic natural scientists and philosophers of the 9th-11th century. PMID- 7995230 TI - Further studies by Christoph Scheiner concerning the optics of the eye. AB - The physician, mathematician and astronomer was born in 1573 in Wald near Mindelheim in Swabia, Germany. He died in 1650 in Neisse in Silesia. He discovered the sun spots and also dealt with the physiological optics of the eye. Further observations of Scheiner's are represented, i.e. from his books Oculus and Rosa Ursina, concerning the anatomy of the eye, the crossing of the beams through a small opening (Camera obscura), stenopeic effect, proof that the crossing of the visual beams takes place in the eye, description of the cataract and its treatment, Christoph Scheiner's eye model, the visual angle, the rotational centre of the eye, the comparison of the optics of the eye and the telescope. PMID- 7995231 TI - On the invention of the ophthalmoscope. AB - The author offers an English translation of three passages of Purkinje's Commentatio de examine physiologico organi visus (1823). He shows that Purkinje made three inventions: (1) by using a transparent mirror, (2) by anticipating Maxwellian illumination, and (3) by providing the first recorded ophthalmic examination of animal and human eyes. PMID- 7995233 TI - A contribution to the history of spectacles in Croatia. AB - The earliest data on spectacles in Croatia originate from the 14th century. Inventories of personal belongings and valuables of distinguished individuals testify about the existence of spectacles from the 14th century onward. Pictorial representations of spectacles and spectacle cases are found in Croatia in various forms: as a watermark in a 14th century paper, on a silver altar-piece from 1477, on paintings, frescoes and wood-cuts from the 15th century onward. A pair of 16th century spectacles are kept in Split (Poljud) and a selection of 18th to 20th century spectacles are on display in various museums in Croatia. In 17th century literature the effect of lenses on ametropia is discussed and Latin and Croatian terms for spectacles and opticians are mentioned. PMID- 7995232 TI - D.B. Kagenaar and the ophthalmometer by Javal-Schiotz. AB - In the years 1881-1890 the Utrecht instrumentmaker D.B. Kagenaar, laboratory attendant of Donders and Snellen, played an important role in the introduction on the German market of the ophthalmometer developed by Javal and Schiotz. PMID- 7995234 TI - Pissarro, dacryocystitis, and the development of modern lacrimal surgery. AB - The co-founder of French Impressionism, Camille Pissarro, suffered from chronic dacryocystitis for at least fifteen years. This kept him from working for long periods of time, and when he was able to work, influenced his method of painting. Pissarro just missed the modern period of lacrimal surgery, and was treated by conservative methods. PMID- 7995235 TI - Didymus the blind: an unknown precursor of Louis Braille and Helen Keller. AB - The present study presents the case of Didymus the Blind, worthy author, philosopher and theologian of the 4th century AD. Blinded by ophthalmia at the age of four years, Didymus succeeded in achieving great learning in the philosophical and natural sciences. He began his education by using a system which was remarkably like Braille, that is reading letters engraved into the surface of wood by touch and subsequently furthering his knowledge by listening. This learning process of Didymus the Blind appears as the precursor of Louis Braille who invented the educational system of reading embossed dots by touch. Like Didymus, Braille lost his vision in infancy (at three years of age). Another parallel of Didymus' career and written works is found in the example and achievements of Helen Keller. PMID- 7995237 TI - Coronal leakage as a cause of failure in root-canal therapy: a review. AB - This paper reviews the evidence that coronal leakage of root canals may lead to failure of root-canal therapy. The causes of coronal leakage and methods by which this leakage may be prevented are described. PMID- 7995236 TI - Further ophthalmological information on Byzantine chroniclers and historians. AB - The historical importance of information on ophthalmological topics by Byzantine chroniclers and historians prompted us to enlarge our researches on this subject. Thus we present 17 various subjects in continuation of our previous article published in Documenta Ophthalmologica, 'History of Ophthalmology' (Vol. 5, 121 132, 1992). PMID- 7995238 TI - Effect of dowel space preparation on the apical seal of root canal fillings. AB - The effect of post preparation on the apical seal was studied using simulated root canals. The maximum level of removal was tested with residual fillings 1, 2, 3, and 4 mm long. All of the artificial canals were filled with gutta-percha, Grossman's sealer, and lateral condensation. The removal was immediate and carried out with warm pluggers and the dowel space was completed with a Peeso drill. Stainless steel posts were cemented with zinc phosphate cement in the free space of the root canals. The coronal access of the canals was sealed with temporary fillings. After setting the materials, the specimens were immersed in a 2% methylene blue dye solution for 72 h and were observed with a measuring microscope. The final length of the apical fillings was found to be different from the intended length in every group. As far as leakage was concerned, 1, 2, and 3 mm-long fillings did not show a significant difference when compared with the negative control group (that is to say, filled canals where no dowel space was created). In the 4 mm fillings the leakage value was zero. These findings may be of clinical importance when restoring short roots. PMID- 7995239 TI - Histological observations of hard tissue barrier formation in amputated dental pulp capped with alpha-tricalcium phosphate containing calcium hydroxide. AB - This study was performed to evaluate the pulpal response to alpha-tricalcium phosphate (alpha TCP) containing calcium hydroxide (Ca(OH)2). The dental pulps of monkeys were amputated and dressed with four agents: alpha TCP, alpha TCP containing 1% Ca(OH)2, alpha TCP containing 5% Ca(OH)2, and Ca(OH)2 being used as a control. The pulpal responses were histologically evaluated after 4 and 8 weeks. The pulp tissue treated with alpha TCP proliferated above the level of the original wound surface, and a thin layer of hard tissue barrier was formed directly against the capping agent. The barrier demonstrated atubular matrix lined with flattened or cuboidal cells, but occasionally appeared irregular in form. Ca(OH)2 dressing resulted in destruction of pulp tissue, with a thick hard tissue barrier being formed below the level of the exposure site. The barrier consisted coronally of osteodentin and pulpally of tubular dentin lined with odontoblast-like cells. By contrast, 1% Ca(OH)2 added to alpha TCP produced a slight proliferation of pulp tissue. An atubular matrix barrier, pulpally lined with cuboidal cells, formed above the exposure site. It was later followed by the formation of tubular matrix lined with columnar cells. Teeth treated with 5% Ca(OH)2 showed a thin necrotic layer and a thick barrier formation. The barrier was composed of tubular dentin-like tissue lined with odontoblast-like cells. It would appear that alpha TCP containing a small amount of Ca(OH)2 may be clinically useful as a capping agent, as it induced consistent hard tissue formation, without excessive destruction of underlying pulp tissue. PMID- 7995240 TI - Immunohistochemical examination on the localization of macrophages and plasma cells in induced rat periapical lesions. AB - To investigate the role of plasma cells and macrophages in the development of periapical lesions, we immunohistochemically examined the distribution of these inflammatory cells in experimental induced rat periapical lesions after pulpectomy. The number of ED1-positive mononuclear cells increased rapidly, reached a plateau which remained stable between days 10 and 60, and subsequently decreased. Immunoglobulin (Ig)-bearing plasma cells appeared after 60 days, and, of these, IgG-bearing plasma cells were predominant after 90 days. The radiographic and histopathological findings indicated the development of bone destruction at 10 days which continued until 60 days; tissue repair began to take place after 90 days. The results suggested that macrophages had a close relation to bone destruction and that plasma cells might participate in tissue repair rather than the development of periapical lesions. PMID- 7995242 TI - Mineralized deposits in pulps of incompletely developed permanent monkey incisors after pulpotomy with tungsten carbide fissure burs. AB - The exposed pulp of incompletely developed permanent incisors of nine monkeys were treated with partial pulpotomy with tungsten carbide fissure burs on an air turbine equipment. The pulps were capped with calcium hydroxide (Dycal) followed by insertion of conventional amalgam. The results were studied by conventional light microscopy after 1 and 6 months. Rod-like mineralized pulpal deposits were seen in five of the nine animals, in 9 out of 67 teeth, evenly distributed at the two observation times. Also the lengths of the deposits appeared similar, while the thickness had increased markedly after 6 months. After 1 month the presence of a central vessel lumen was observed in the deposits. The results seemed to indicate that the mechanism of formation was an initial pathologic mineralization of the vessel wall, and a growth of the deposits by the elaboration of fibrous, atubular dentin on to the outside of this wall. PMID- 7995241 TI - Cytotoxicity of potential retrograde root-filling materials. AB - The cytotoxicity of potential retrograde root-filling materials was assessed using the Millipore filter method. A light-cured glass ionomer cement, Vitrebond (VB), and three reinforced zinc oxide-eugenol cements, Kalzinol, IRM and ethoxybenzoic acid (EBA) cement, were compared with amalgam. Twenty standardized pellets of each material, 10 fresh and 10 aged by storage in sterile distilled water for 72 h were produced. Ten filters were included as controls: five filters with a cell monolayer, but without test specimens, and another five without cells but with test specimens. Fresh IRM exhibited the most pronounced cytotoxic effect and the difference was statistically significant compared with all the other materials. There was no statistically significant difference between fresh VB, Kalzinol, EBA cement and amalgam. When aged, Kalzinol was the most cytotoxic and the difference was statistically significant compared with the other materials. Aged IRM was the second most cytotoxic material and this too was statistically different. The cytotoxicity of VB, EBA, and amalgam did not differ significantly from one another. PMID- 7995243 TI - An in vitro investigation of Thermafil obturation at different temperatures. AB - The apical leakage of lower premolars obturated with Thermafil at three different temperatures was investigated in vitro. The temperatures were determined after calibration of the Thermaprep oven. The root canals of 35 extracted teeth were prepared chemomechanically and divided into three groups of 10 each with a control group of five. The root canals of the experimental group were obturated using plastic Thermafil obturators at three different temperatures 144, 120 and 100 degrees C with the controls being obturated using laterally condensed gutta percha. The teeth were suspended in indian ink for 28 days prior to being cleared and the degree of apical leakage assessed. The results showed no significant difference (p > 0.05) in the apical leakage of the teeth obturated with Thermafil compared to laterally condensed gutta percha. There was a trend towards less leakage in the teeth obturated with Thermafil at the lower temperatures, this, however, was not significant (p > 0.05). PMID- 7995244 TI - Effect of inferior alveolar nerve block anaesthesia on the lower teeth. AB - The aims of this study were to investigate the effects on pulpal blood flow and anaesthesia in mandibular teeth during inferior alveolar nerve block anaesthesia using 2% lignocaine with 1:80,000 adrenaline in 10 adult human subjects. Local anaesthetic solution was delivered close to the inferior alveolar nerve at the mandibular foramen using a standardized nerve block technique. The pulpal blood flow of the canine and first permanent molar was monitored by a laser Doppler flowmeter. At selected times pulpal anaesthesia was tested with an electric pulp tester. The injection of 2 ml of solution caused a decrease in pulpal blood flow in both teeth in every subject. The reduction in blood flow was of shorter duration than pulpal and soft tissue anaesthesia. A period of increased blood flow following the period of reduction was noted in several subjects. The mean reduction in pulpal blood flow in the canine at 15 min was 48% and lasted for a mean of 93 min. In contrast, the mean reduction in pulpal blood flow in the molar at 15 min was 25% and of 72 min mean duration. The mean duration of pulpal anaesthesia was 114 min in the canine compared with 88 min in the molar. Full soft tissue anaesthesia lasted for a mean of 151 min, whereas complete recovery took 255 min. This study indicated that lignocaine and adrenaline in block anaesthesia acted not only at the site of injection but also within the individual teeth. PMID- 7995245 TI - Splinting of avulsed central incisors with orthodontic wires: a case report. AB - A case of an 8-year-old boy who met with a road traffic accident causing trauma to the body and face and extrusion of the upper central incisors is reported. Laceration, oedema and limited mouth opening indicated the use of general anesthesia. During intubation the right central was avulsed accidentally and the left central further luxated and rotated. The avulsed central was reimplanted and the other one derotated and stabilised with orthodontic wire and brackets. Twelve weeks later the patients teeth were firm, immobile, radiographically normal and responded positively to vitality test. PMID- 7995246 TI - Encoding of the subjective intensity of sharp dental pain. AB - This paper is a review and a discussion of our own pain research over the last decade. It is of a methodological and theoretical character and deals with preparation technique, choice of electrodes, control experiments involving pulpotomy and reliability tests of psychophysical methods for pain measurements, and the neuronal population encoding of sharp dental pain. The electrophysiological recording technique selectively picks up electrical activity induced in pulpal A-delta nerve fibers. The sensation of pain was quantified by means of an intermodal matching technique, finger span (PAS), in combination with sensory verbal descriptors covering a range from very, very weak to maximal pain. When a cold stimulus, ethyl chloride, was applied on the tooth surface a close agreement was demonstrated between intradental A-delta nerve activity (INA) and the sensation magnitude of pain (PAS) with respect to curve amplitude and time course. The high covariation of the neural and perceptual response measures indicated a good internal validity and confirmed also the basic soundness and the applicability of the procedures employed. For the purpose of further analyzing the functional relation of INA to PAS we studied specifically the effect of cold stimuli of different intensity on the integrated nerve response. Only sharp, shooting pain was accepted as a sensorial, perceptual correlate of the intradental A-delta nerve activity. Since an increase in amplitude was generally accompanied by an increase in duration of the responses, the fundamental question was raised how to best describe and characterize the neural and perceptual responses so that they most adequately reflect the information processing of the intensive aspect of sharp dental pain.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7995247 TI - Adrenaline in local anaesthesia: the effect of concentration on dental pulpal circulation and anaesthesia. AB - This study investigated the effects of inferior alveolar nerve block anaesthesia using 2% lignocaine with 1:100,000 or 1:80,000 adrenaline on pulpal blood flow in mandibular molar and canine teeth in 10 human subjects by laser Doppler flowmetry. The duration of pulpal anaesthesia in the teeth using electric pulp testing was also investigated. The injection of 2 ml of 2% lignocaine with 1:100,000 adrenaline caused a decrease in pulpal blood flow in both teeth in every subject. The mean pulpal blood flow in the canine tooth at 15 min was 58% of the baseline value whilst that in the molar was 76%. These values were not significantly different from the reduction in pulpal blood flow produced by 2% lignocaine with 1:80,000 adrenaline. Both solutions produced a reduction in blood flow that was of shorter duration than pulpal and soft tissue anaesthesia, and of shorter duration in the molar tooth compared with the canine. When 2% lignocaine with 1:100,000 adrenaline was injected, the mean reduction of blood flow was of shorter duration (canine, 60 min; molar, 42 min) than following 2% lignocaine with 1:80,000 adrenaline (canine, 93 min; molar, 72 min); these differences in reductions were statistically significant (P < 0.05). Using 2% lignocaine with 1:100,000 adrenaline, the mean duration of pulpal anaesthesia was 76 min in the canine tooth compared with 58 min in the molar tooth. Full soft tissue anaesthesia lasted for 117 min. These values were reduced significantly when compared with the lignocaine solution containing 1:80,000 adrenaline (P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7995248 TI - Reaction of rat subcutaneous tissue to implants of gutta-percha for endodontic use. AB - The present work studied the reaction caused in the connective tissue of rats by implantation of two brands of gutta-percha cones, and thermoplasticized gutta percha cylinders. Thirty-six rats were used, in groups of 12, for periods of 15, 30, and 60 days. Each animal received one test implant of each material, and one implant of Teflon as control. The cylinders, and one of the brands of gutta percha cones, were well tolerated by the connective tissue. The cones of the other brand elicited different reactions, of which the possible causes are herein discussed. PMID- 7995249 TI - A study of forces originating from orthodontic appliances for splinting of teeth. AB - Management of dental trauma in children sometimes requires the use of a dental splint. This can be constructed with composite materials, kevlar, fiberglass, wire and composite or orthodontic wires and brackets. However, there have been no studies of the control of dental movement when orthodontic materials are used for a dental splint. The purpose of this study was to determine the forces exerted by an orthodontic appliance used as a dental splint. To measure such forces, a transducer with a detection of 0.01 N (+/- 5%) was inserted into a maxillary dental arch model. The results showed that the orthodontic wire was rarely passive and the forces developed ranged from 0 to 27 x 10(-2) N. The force developed was independent of the length of the dental splint (p < 0.05) and wire size (p < 0.05). The mean force developed by nickel-titanium wires (14.27 x 10( 2) N) was significantly greater (p < 0.05) than the mean force developed by stainless steel and cobalt-chromium wires. Moreover, the mean force developed by rectangular wires (12.07 x 10(-2) N) was significantly greater (p < 0.05) than the mean force developed by square and round wires. The results suggested that stainless steel or cobalt-chromium, square or round wires should be used for construction of a dental splint. PMID- 7995250 TI - Reliability of laser Doppler flowmetry in testing vitality of human teeth. AB - The aim of this investigation was to study the reliability of the laser Doppler flowmetry (LDF) output signals when testing from 4 different positions on the buccal surface of human teeth. Recordings were made from 10 intact anterior teeth in 10 patients, mean age 27.4 years. Five types of probes were used. Each probe had 3 fibers arranged in a triangle, one lighted fiber and 2 receiving ones. The separation of the fibers was 1500, 1000, 800, 500 and 250 microns. The diameter of the fibers was 200 microns in all probes except the one with the smallest separation of fibers where it was 125 microns. A rubber base splint was used to position the probe on the buccal surface of the teeth tested. The first recording was made with the ingoing light in a gingival position. Then 3 additional recordings were made turning the probe 90 degrees each time consequently changing the position of the ingoing light accordingly. Thus, gingival, mesial, incisal and distal recordings were obtained. The output signals were fed into a lap-top computer upon which all calculations were done. The output signals from the incisalmost position of the teeth were significantly lower than the output signals from the other 3 positions with all probes except one. The turning of the probes into the 4 different positions affected the output signals from the probe with the smallest separation of fibers significantly more than the output signals from the other probes. PMID- 7995251 TI - Incidence of dentoalveolar injuries in hospital emergency room patients. AB - A retrospective survey over one year of a hospital emergency room population, seen at an oral and maxillofacial surgery clinic, found 271 patients (4.6% of the total population) with dentoalveolar injuries. A very large number of injuries occurred to children between the ages of 0 and 5 years (42.1%), and there was a significant number of injured patients in the adult population (19.1%). The ratio of male to female was 1.9:1. The leading cause of injury was falls (59.8%). The largest number of injuries was seen during summer. The diagnoses were lateral luxation (27.3%), concussion (17.3%), exarticulation (14.3%), tooth fracture (12.5%), intrusive luxation (11.1%), fracture of alveolar process (7.4%), extrusive luxation (3.7%), and cases with more than one diagnosis (6.3%). Most of the involved teeth were maxillary central incisors, in both dentitions. PMID- 7995252 TI - Accidental damage to incisors amongst Irish adults. AB - Evidence of accidental damage to permanent incisor teeth was recorded as part of a national survey of adult dental health in Ireland. A total of 746 adults aged between 16 and 34 years were examined. The prevalence of injury was considerably higher in males and the majority of subjects in both sexes had just one tooth affected. There was a continuing increase in prevalence with age which appeared to level out after the age of 24. A high level of untreated injuries was noted in both age groups; of those injuries which were treated, composite restorations were more common in the younger age groups while extraction and replacement by a denture was more common in older subjects. PMID- 7995253 TI - Extraoral tooth eruption and transposition of teeth following trauma. AB - A six-year-old boy presented with extraoral eruption of a mandibular permanent canine and a loosely attached lateral incisor in the labial vestibule, 3 months following trauma to the chin. The trauma not only caused displacement of the permanent tooth buds, but also resulted in transposition of the lateral incisor and canine with subsequent ectopic eruption. The case is presented to demonstrate one of the infrequent complications of trauma involving the unerupted tooth buds of permanent teeth and its unusual clinical presentation. PMID- 7995254 TI - Trigeminal neurapraxia following a blow to the face: a case report. AB - Examination of the cranial nerves is a simple and valuable procedure following trauma to the head and neck. By understanding their courses, branches and distributions, the site of any damage may be localized. Once the site and nature of injury has been determined, correct management may be instigated. A case is presented in which there was some degree of trigeminal nerve damage following trauma. The site of damage was determined to be extracranial and therefore a conservative regimen adopted. The mechanism of injury is postulated. PMID- 7995255 TI - Dietary iodine affects epidermal growth factor levels in mouse thyroid and submaxillary glands. AB - To determine whether dietary iodine intake affects the levels of immunoreactive epidermal growth factor (EGF) in vivo in two mouse tissues known to be thyroid hormone responsive, 24 adult BALB/c mice were randomized into groups of six animals and fed a) an iodine-deficient diet, b) normal laboratory chow (controls), c) an iodine-deficient diet with high physiological iodine supplementation (approximately 300 micrograms/day), and d) an iodine-deficient diet with pharmacological doses of iodine (approximately 3 mg/day). After 21 days on the various regimens, the mice were killed and the concentration of mouse (m) EGF in the thyroid and submaxillary glands (SMG) measured by radioimmunoassay. The mean (+/- SEM) SMG mEGF level (micrograms/mg wet weight) in the different groups were: a) 7.58 +/- 1.87, b) 12.46 +/- 4.7, c) 19.79 +/- 4.47, and d) 24.36 +/- 5.96. The thyroid mEGF concentrations (ng/mg wet weight) were: a) 3.65 +/- 0.75, b) 5.23 +/- 1.84, c) 8.07 +/- 1.18, and d) 6.43 +/- 0.95, respectively. Analysis of variance revealed that dietary iodine status had a significant effect on mEGF levels in both the SMG (p < 0.001) and the thyroid gland (p < 0.001). Compared to controls, tissue mEGF levels decreased by 30-40% in the mice fed an iodine-deficient diet, and increased by 60-150% following physiologic iodine replacement. PMID- 7995256 TI - Cytochrome P-450 levels of immature rat ovaries during early follicular development: quantification, cellular and subcellular distribution, enzymatic activity and response to FSH in vivo and in vitro. AB - Absolute values of cytochrome P-450 (cyt. P-450) content were determined by dual beam spectrophotometry in mitochondrial and microsomal fractions of granulosa cells and stroma (theca and interstitial cells) obtained from ovaries of immature rats treated with diethylstilbestrol (DES) or with DES and FSH. Cholesterol side chain cleavage activity and aromatase activity were also measured in relevant cell fractions. The cyt. P-450 content in the granulosa cell mitochondria was significantly increased in FSH-treated animals (cyt.P-450 in nmols/mg protein, mean +/- SE: DES-treated 0.027 +/- 0.00213, N = 9; DES/FSH-treated 0.0668 +/- 0.0120, N = 13, P = 0.014). The increased cyt. P-450 content was associated with an increase in cholesterol side-chain cleavage activity confirming the functional relevance of the spectrophotometric measurements. The increase in cyt. P-450 content in stroma after FSH treatment was not statistically significant but there was a significant increase in cholesterol side-chain cleavage activity. The cholesterol side-chain cleavage activity of intact granulosa cells from secondary follicles of DES-treated rats was significantly stimulated by in vitro exposure to FSH during 2 hr assay incubations. A significant cyt. P-450 content was detected in the microsomal fraction of granulosa cells from DES-treated rats which was not associated with aromatase activity. Granulosa cell microsomal cyt. P-450 content was not significantly altered by in vivo FSH treatment despite a dramatic increase in aromatase activity of such microsomal preparations. PMID- 7995257 TI - Activities and androgenic regulation of kreb cycle enzymes in the epididymis and vas deferens of rhesus monkey. AB - The activities of nine enzymes of the TCA cycle were estimated in the initial segment, caput, corpus and cauda segments of epididymis and vas deferens of adult rhesus monkey and expressed as units per mg DNA. These enzymes were also estimated in epididymal segments and vas deferens of castrated and castrated androgen replaced monkeys as well. Results indicated higher activities of most of the enzymes in vas deferens as compared to epididymal segments. All the enzymes showed marked reduction in epididymis and vas deferens after castration, the effect being much more pronounced in the epididymis, than in the vas. Androgen replacement in castrated monkeys stimulated most of the enzymes markedly in epididymis and in the vas deferens as compared to their castrated values. The response of cauda and vas deferens to exogenous androgen treatment was however moderate, as compared to the other epididymal segments. The studies indicate that energy metabolism in the epididymis (as well as in the vas deferens) is strictly androgen dependent and the energy charge of these target organs is likely to fall appreciably after castration, which may in turn affect many energy dependent processes of these organs (e.g. absorption, secretion of specific substances etc.) which have been considered important for sperm maturation and survival. PMID- 7995258 TI - T lymphocyte activation in Graves' disease. AB - We examined the proliferative response of T lymphocytes from thirty-eight patients with Graves' disease (17 untreated thyrotoxic and 30 euthyroid on antithyroid medication) to phytohemagglutinin, anti-CD3 MoAb and phorbol esters, as well as the capacities of these lymphocytes to produce interleukin 2 and the density of interleukin 2 receptors and major histocompatibility class II antigens. We found that the response of T lymphocytes to phytohemagglutinin, anti CD3 monoclonal antibody and phorbol esters from untreated thyrotoxic Graves' disease was significantly enhanced as compared to treated patients and normal controls. Interleukin 2 production by mitogen-triggered T lymphocytes in both treated and untreated patients with Graves' disease was comparable to that of the control population. Interleukin 2 receptor density was found to be normal, whereas that of human leukocyte antigen-DR was increased in both untreated and treated patients. Following lymphocyte stimulation, there was an increase in human leukocyte antigen-DR and interleukin 2 receptor expression in patients with untreated Graves' disease. Significant correlations were found between thyroid hormone concentration and the proliferative responses to the polyclonal mitogen phytohemagglutinin, anti-CD3 monoclonal antibody and phorbol esters in untreated Graves' patients. Furthermore, during the follow-up of 9 patients, attainment of normal thyroid function after antithyroid treatment was associated with a decrease in and normalization of T-proliferative responses. Our data reveal that active Graves' disease is associated with T cell activation and this is probably related to immunological dysregulation as well as to hyperthyroxinemia. PMID- 7995260 TI - Polyunsaturated fatty acids and antioxidants in early development. Possible prevention of oxygen-induced disorders. PMID- 7995259 TI - Long-chain polyunsaturated fatty acids in infant nutrition. PMID- 7995261 TI - Infant cerebral cortex and dietary fatty acids. PMID- 7995262 TI - Long-chain fatty acids and early visual and cognitive development of preterm infants. AB - Preterm infants fed formula supplemented with DHA were shown in two randomized, clinical trials to have improved visual acuity in the first half of infancy. In the second clinical trial, infants simultaneously supplemented with DHA and provided with a nutrient-enriched preterm formula had a higher Bayley MDI score at 12 months than controls fed preterm formula. These data are the first evidence that DHA alone can also improve performance on early tests of mental development. Because visual and behavioural development are improved by providing this single dietary compound, DHA appears to be conditionally essential for preterm infants. Nevertheless, we would like to insert a few words of caution. More information about long chain n-3 and n-6 fatty acid requirements and balance for developing human infants is needed. As formulas are designed to meet n-3 and n-6 fatty acid needs, controlled studies of biochemistry and function should continue. PMID- 7995263 TI - Status of clinical trials with the long-chain polyunsaturated fatty acid infant formula Aptamil with Milupan. PMID- 7995264 TI - Dietary fats and gastrointestinal function. PMID- 7995265 TI - Beta-blockers in cardiac failure. AB - The use of beta-blocking agents in patients with heart failure is still controversial. An activated sympatho-adrenal system in heart failure may support blood pressure and cardiac index, on the other hand, it increases cardiac load and myocardial oxygen consumption, reduces myocardial oxygen supply and may contribute to the high incidence of arrhythmias and sudden death. Today there is a certain awareness about the important role of the sympatho-adrenal system in CHF. Short-term studies failed to demonstrate a benefit of beta-blockers while long-term studies have proved major haemodynamic benefit and functional improvement in most patients. The haemodynamic benefit consists of a reduction of heart rate and left ventricular filling pressure and an improvement in exercise capacity. The mechanism of these actions of beta-blockers, with the exception of lowering heart rate, remains unclear. Energy metabolism of the failing heart, which is considered to be deficient, may beneficially be influenced by chronic beta-blocker treatment. Effects of beta-blockers on prognosis in patients with heart failure are also still controversial. Most recent trials (MDC Trial, CIBIS Trial) were inconclusive concerning mortality. Aetiology of heart failure may be important; however, observations on secondary prevention post-myocardial infarction also contradict heart failure studies. Thus, further efforts are urgently needed to define the mechanism of action of beta-blockers in patients with cardiac failure and to identify more clearly patients who benefit from this type of therapy. PMID- 7995266 TI - Peripheral vascular effects of beta-blockers. AB - This review addresses the vascular effects of beta-blockers in patients with normal peripheral circulation, with hypertension or with peripheral arterial disease. Despite conflicting data from many uncontrolled and relatively small studies some general conclusions can be drawn. In the absence of peripheral vascular disease there is no good evidence of any adverse effects of beta-blocker treatment on peripheral circulation. Nevertheless, it may be useful to change from non-selective to beta-1 selective beta-blockers or to beta-blockers with ISA when patients complain of cold extremities. In hypertensive patients, beta blocker therapy may similarly cause cold extremities, especially with non selective beta-blockade. Successful long-term antihypertensive treatment, as with beta-blockers, may restore normal vascular architecture. In patients suffering from peripheral arterial disease, beta-blockers are not generally contraindicated although they should be administered with extreme caution when disease is severe. In less severe forms of occlusive disease, beta-blockers have little effect on peripheral circulation and may even improve flow to the diseased area by an inverse steal effect. PMID- 7995267 TI - Late potentials and heart rate variability in heart muscle disease. AB - To elucidate the incidence and clinical significance of ventricular late potentials (LP) and reduced heart rate variability (HRV) in primary and secondary heart muscle disease, 157 patients with dilated cardiomyopathy (DCM, n = 19), chronic myocarditis (MC, n = 50), hypertrophic cardiomyopathy (HCM, n = 27) and systemic hypertension (HT, n = 61) were studied. LP measured by the signal averaging technique were found in 24% of the total study group--47% of the patients with DCM, 28% with MC, 29% with HCM and 10% with HT. Complex ventricular arrhythmias were detected during Holter monitoring in 56% of patients with DCM, in 41% with MC, in 21% with HT and in 16% with HCM. An electrophysiological study was performed in a total of 75 patients. Non-sustained or sustained ventricular tachycardia (VT) or ventricular fibrillation (VF) were inducible during programmed ventricular stimulation in 32% of patients with MC, in 30% with HT, in 20% with DCM and in 17% with HCM. The total duration of the signal-averaged, filtered QRS complex was the only independent predictive factor for severe arrhythmic events and sudden cardiac death. HRV measured in 39 patients were most reduced in patients with DCM (RR interval standard deviation (HRV-SD) 39 +/- 23 ms), followed by 44 +/- 16 ms in patients with HCM, 45 +/- 28 ms in patients with HCM and 67 +/- 51 ms in patients with HT. A significant reduction in the HRV-SD below 30 ms was recorded in 24% of patients measured.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7995268 TI - Ventricular late potentials: state of the art and future perspectives. AB - Although the signal-averaging technique is over one hundred years old, its first use was demonstrated on the human heart in 1963 and ten years later recording of His bundle potentials from the body surface became feasible. During the last decade interest has been focused on ventricular late potentials (LP) which represent zones of delayed myocardial activation occurring in hearts after myocardial infarction as well as in diffusely damaged myocardium. Presentation of LP in the 'time domain analysis' is highly standardized and widely accepted. Development of spectral analysis techniques is still advancing and promises not only a more sophisticated interpretation of LP but also detection of electrical disturbances during the whole QRS complex. In clinical cardiology LP are found in 10% to 50% of all cardiac diseases, mainly in coronary heart disease and dilated cardiomyopathy. About 80% of patients with sustained ventricular tachyarrhythmia demonstrate LP. Their value as predictive of arrhythmic events and sudden cardiac death is relatively low (10-30%), but very high in predicting a good outcome, showing 95% event free survival if LP are negative. Predictive accuracy can be enhanced by a combination of independent indices, particularly heart rate variability. Other clinical applications are prediction of patency of the infarct related artery after thrombolysis or after angioplasty in acute myocardial infarction and prediction of success after guided anti-tachycardiac surgery. No consistent changes can be observed following elective revascularization by angioplasty or bypass surgery. Ischaemia, exercise and manipulation of autonomic tone apparently do not consistently influence LP if ensemble signal-averaging is applied, but may cause transient alterations detectable by beat-to-beat analysis. Potential future directions are (1) evaluation of spectral analysis techniques, (2) improvement of the predictive value by combining time and frequency domain analysis, (3) increased application of beat-to-beat analysis in different pathophysiological conditions, (4) enhanced diagnosis of high-risk patients by combining other independent arrhythmic indices with LP, (5) specific selection of patients for invasive electrophysiological testing and (6) the study of LP shifting during long-term therapy of heart hypertrophy, failure, inflammation and ischaemia. Dynamic or functional LP analysis during exercise testing, electrophysiological investigation or coronary angioplasty may be a further application. PMID- 7995269 TI - Cardiac late potentials for diagnosis in heart disease. AB - In recent years abundant information has been obtained about the relationship of heart disease and cardiac late potentials. Non-invasive recordings of ventricular late potentials are useful in risk stratification of various clinical conditions, in particular, in patients following myocardial infarction. Here a close correlation has been established between cardiac late potentials and spontaneous or induced sustained ventricular tachycardias using programmed electrical stimulation. Cardiac late potentials also appear to be associated with arrhythmic events in patients with cardiomyopathies, and following unsuccessful antitachycardia surgery. Furthermore, recording of abnormal late potentials are associated both with acute rejection after cardiac transplantation and unsuccessful thrombolytic therapy after myocardial infarction. Interestingly, antiarrhythmic drugs have no clear effect on cardiac late potentials. PMID- 7995270 TI - ACE inhibitors and their influence on inflammation, bronchial reactivity and cough. AB - Orally active angiotensin converting enzyme (ACE) inhibitors have been successfully used in the treatment of congestive heart failure and hypertension. However, adverse skin reactions, such as angioneurotic oedema have been reported following such medication. Furthermore, these drugs have been associated with a persistent dry cough in subjects without previous known bronchial hyper reactivity. There is reason to believe that an ACE inhibitor-induced cough is due to an irritant inflammatory state in the airways of susceptible individuals and that this might have pathophysiological features in common with the cough seen as an early symptom of asthma. All inflammatory responses--wheal and flare reactions, airway reactivity, and infiltration by neutrophils and eosinophils- were enhanced by ACE inhibitors in a dose-dependent manner. Other ACE inhibitors might have different proinflammatory profiles. PMID- 7995271 TI - Infection and intimal thickening: evidence from coronary arteries in children. AB - Post-mortem examination in children may reveal narrowing of coronary artery diameter by up to 60% due to intimal thickening. This is statistically associated with recent or intercurrent infection. Endothelial injury is known to be caused by septicaemia, for example, and endothelial injury initiates atherogenesis. Elevation of tumour necrosis factor alpha (TNF alpha) levels is a feature of both septicaemia and atheroma, and TNF alpha can damage endothelium, stimulate platelet-derived-growth-factor (PDGF) secretion and thereby promote vascular smooth muscle cell proliferation. Episodes of infection-related endothelial damage, leading to intimal thickening followed by partial regression, may start in infancy and contribute cumulatively to the development of coronary atheroma. PMID- 7995272 TI - Immunohistological characterization of infiltrating lymphocytes in biopsies of patients with clinically suspected dilated cardiomyopathy. AB - Experimental and clinical data suggest a relationship between myocarditis and dilated cardiomyopathy. One postulated mechanism is a viral infection triggering a host response with autoimmune features directed against the heart, resulting in an initial myocarditis which is followed by dilated cardiomyopathy. Until now, the importance of myocarditis as an aetiological factor in the pathogenesis of isiopathic cardiomyopathy has been unknown. This investigation was undertaken to determine immunohistologically the frequency of lymphocytic infiltrations in endomyocardial biopsies of patients with clinically suspected dilated cardiomyopathy. T-lymphocytic subsets and other immunological features were also analysed to explore possible relationships between immunohistologically documented myocarditis and dilated cardiomyopathy. PMID- 7995273 TI - Pericardioscopy and epicardial biopsy--new diagnostic tools in pericardial and perimyocardial disease. AB - Pericardioscopy is a new diagnostic tool for macroscopic visualization of alterations in both the epicardium and pericardium. We report on 35 patients with pericardial effusion due to inflammatory perimyocardial disease. After puncture of the pericardial effusion, an 8F sheath was introduced over a guidewire under X ray control. The pericardial pressures were measured; the fluid was removed by aspiration and exchanged with 100 ml of body-warm saline until the pericardial fluid was clear. To visualize the peri- and epicardium, for video- and photo documentation, two sorts of 8F endoscope were used, either a flexible fibreglass version or a rigid 110 degree one--both made by Storz. Cytology of the fluid and optically guided and controlled epicardial and pericardial biopsies were performed to classify the form of pericarditis. A specific diagnosis of viral pericarditis could thus be established in seven cases--by in situ hybridization for cytomegalovirus (n = 3) and by microneutralization test for enteroviruses and/or coxsackievirus B4 isolation (n = 4); of lymphocytic perimyocarditis in 16; of bacterial pericarditis in seven and antibody-mediated autoreactive pericarditis in five cases. PMID- 7995274 TI - The clinical significance of insulin resistance in the treatment of hypertension. AB - A strong association between arterial hypertension and Type 2 diabetes mellitus has been known for more than 70 years. However, there are many unanswered questions with regard to the hypothesis of a causal relationship between insulin resistance/hyperinsulinaemia and arterial hypertension. At present, there is no hard evidence for a close (causal) linkage between insulin resistance (or hyperinculinaemia) and arterial hypertension. Currently available antihypertensive drugs in prudent and effective dosages do not result in a deterioration of insulin sensitivity, or in the development of insulin resistance, or an increased incidence of Type 2 diabetes mellitus. PMID- 7995275 TI - New aspects of insulin resistance in hypertension. AB - Primary hypertension is a frequent polygenic disease with strong genetic and environmental components. During the last decade, evidence has been increasing that insulin resistance as a marker of increased risk for Type 2 diabetes and cardiovascular atherosclerotic disease is present not only in individuals with obesity, Type 2 diabetes and impaired glucose tolerance, but also in the majority of the hypertensive population. Insulin resistance describes a tissue- and pathway-specific defect of glucose metabolism present in the so called 'metabolic syndrome'. Hyperinsulinaemia compensates for insulin resistance, leading to a cluster of undesirable processes predisposing to diabetes, atheroma and, directly or indirectly, hypertension. Candidate mechanisms whereby this metabolic syndrome might lead to hypertension include renal sodium retention, vascular hyperresponsiveness, arteriolar smooth muscle cell proliferation, altered cellular electrolyte transport and composition, stimulation of sympatho adrenergic activity and growth promoting effects. Insulin per se does not appear to be the cause of elevated blood pressure as frequently seen in insulin resistant states, but it may act with other factors to promote hypertension and atherosclerotic cardiovascular disease. PMID- 7995276 TI - Anti-atherosclerotic effects of beta-blockers. AB - Mechanisms involved in the development of atherosclerosis are reviewed. Based primarily on experimental studies, the following key steps are suggested; (1) endothelial injury; (2) platelet and leukocyte adhesion; (3) smooth muscle proliferation; (4) lipid deposition; (5) arterial tissue hypoxia. Beta-blockers may interfere with (1), (2), (4) and (5), and have been shown to inhibit experimental atherosclerosis, even if given after the disease has been established. Calcium channel and ACE inhibitors interfere with (2), and have been shown to inhibit experimental atherosclerosis if given throughout the experimental period. It is unclear whether the association between hypertension and atherosclerosis is causal. Therefore, antihypertensive agents should be selected according to their potential to interfere with the atherosclerotic process. The primary choice would then be beta-blockers, combined with calcium channel or ACE inhibitors if the patient is considered to be at risk of developing new lesions. PMID- 7995277 TI - Therapeutic potential of potassium channel activators in coronary heart disease. AB - Potassium channel activators have the ability to open potassium channels in a variety of cells. Since most of their effects are antagonized by antidiabetic sulfonylureas, the ATP-sensitive potassium channel is their likely target. Opening of potassium channels leads to hyperpolarization of the surface membrane with consequent closure of voltage-dependent ion channels and reduction of free intracellular calcium ions. Currently available potassium channel activators, including aprikalim, bimakalim, cromakalim, emakalim, nicorandil, pinacidil etc., display a high affinity for potassium channels of vascular smooth muscle. Vasodilation and a reduction in systemic vascular resistance are their prominent pharmacological effects. Coronary and cerebral arteries are highly sensitive to potassium channel activator-induced dilation. Apart from treatment of hypertension, potassium channel activators appear to have therapeutic potential in coronary heart disease. They reduce cardiac afterload, increase native and collateral coronary blood flow and reduce the size of experimental myocardial infarcts. This last effort cannot be satisfactorily explained entirely by haemodynamic or coronary vascular actions of potassium channel activators and a cardioprotective effect is postulated. For these drugs ischaemia-induced and activator-induced opening of cardiac ATP-sensitive potassium channels appear to work in concert. Nicorandil combines the pharmacological properties of an organic nitrate with those of potassium channel activators. Experimental and clinical results characterize nicorandil as a unique and promising drug for the treatment of coronary heart disease. PMID- 7995278 TI - Cardioprotective actions of potassium channel openers. AB - The potential cardioprotective effect of two pure potassium channel openers, bimakalim (EMD 52692) and aprikalim (RP 52891), on myocardial ischaemia/reperfusion injury was investigated in barbital-anaesthetized dogs. In a model of reversible ischaemia/reperfusion injury, administration of bimakalim as an intravenous bolus prior to ischaemia or administration of a non-hypotensive dose of aprikalim as a constant intravenous infusion resulted in a reduction in reperfusion contractile dysfunction (myocardial 'stunning') produced by a single 15-min coronary artery occlusion. Administration of aprikalim only during the reperfusion period had no beneficial effect. Similarly, in a model of irreversible ischaemia/reperfusion injury (90 min of coronary artery occlusion followed by 5 h of reperfusion), intravenous infusion of bimakalim at a dose which reduced aortic blood pressure approximately 15-20 mmHg or infusion of aprikalim at a non-hypotensive dose throughout the entire experiment produced a significant reduction in myocardial infarct size. A protective effect of bimakalim was not observed when it was administered during the reperfusion period only. In both the stunned myocardium model as well as the infarcted myocardium model, the beneficial effects of the potassium channel openers could not be attributed to differences in the traditional determinants of the extent of ischaemia/reperfusion injury; area at risk size, oxygen consumption, or collateral blood flow. Furthermore, the anti-ischaemic actions of the potassium channel openers were blocked by pre-treatment with the ATP-dependent potassium (KATP) channel antagonist, glibenclamide.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7995280 TI - The diagnosis and assessment of an adult with anomalous origin of the left coronary artery from the pulmonary artery. AB - Anomalous origin of the left coronary artery from the pulmonary artery (the Bland White-Garland syndrome) is a rare congenital cardiac defect which may present for the first time in adulthood. The recognition of this disorder, which produces widespread left ventricular ischaemia and the risk of sudden death, myocardial infarction and congestive heart failure, is important as the prognosis can be improved by surgical intervention. Thallium-201 scintigraphy has a useful role in demonstrating the widespread nature of the ischaemia of the left ventricle, whilst the diagnosis is confirmed at cardiac catheterisation. PMID- 7995279 TI - Simultaneous gallium-67 citrate and technetium-99m sestamibi SPET in a case of myocardial lymphoma: comparison with echocardiography before and after chemotherapy. AB - A patient with diffuse large cell lymphoma involving the interventricular septum and the inferior ventricular wall was imaged with a simultaneous dual-isotope single-photon emission tomography (SPET) acquisition technique, using the radiotracers technetium-99m hexakis 2-methoxyisobutylisonitrile (sestamibi) and gallium-67 citrate, in conjunction with echocardiography, prior to and following the first course of chemotherapy. Simultaneous acquisition--with the advantage of displaying corresponding sets of SPET slices without any need for position correction--, supplemented by echocardiography, increased the accuracy of evaluation of the extent of disease and response to treatment. PMID- 7995281 TI - Hepatobiliary scintigraphy in a patient with bilhemia. AB - A 4-year-old child referred for acute jaundice following percutaneous needle biopsy of the liver underwent hepatobiliary scintigraphy. Although all conventional liver tests suggested preservation of hepatocyte function, the tracer uptake in the liver appeared dramatically reduced at scintigraphy and the blood pool activity did not decrease significantly until the end of the study. Visualization of the bile ducts indicated, however, that the tracer was taken up by the hepatocyte and further excreted into the biliary tree. There was no tracer pooling in the biliary tree although no bowel activity was observed, even on delayed images. The association of persistent blood pool activity, bile duct visualization without tracer pooling, and nonvisualization of the bowel was caused by a continuous recirculation of the tracer from the biliary tree into the bloodstream. The presence of a biliovenous fistula was further proven by percutaneous transhepatic cholangiography performed 24 h later. Since 1975, only 16 cases of bilhemia have been reported. To the best of our knowledge the scintigraphic pattern of this rare but life-threatening complication has not previously been reported. PMID- 7995282 TI - Restrictions following iodine-131 treatment--a time for change or more data required? PMID- 7995283 TI - First evaluation of technetium-99m dimercaptopropionyl albumin as a possible tracer agent for ventriculography in a volunteer. AB - Technetium-99m labelled red blood cells (99mTc-RBCs) are the standard radiopharmaceutical for radionuclide ventriculography but suffer from some practical disadvantages such as risk of viral contamination and lengthy preparation (in vitro labelling) or poor labelling efficiency due to patient medication interactions (in vivo labelling). 99mTc-labelled human serum albumin (HSA) is not really a valuable alternative as the activity diffuses too rapidly out of the vascular space due to the weak binding of the radionuclide. We have modified HSA by reaction with N-hydroxysuccinimidyl 2,3-di(S acetylmercapto)propionate (SAMP) to introduce a varying number of 2,3 dimercaptopropionyl (DMP) side chains. The resulting DMP-HSA can be rapidly labelled with 99mTc at room temperature by simple addition of stannous ions and eluate of a 99mTc generator. After evaluation in mice and rabbits, two different 99mTc-DMP-HSA preparations - obtained after reaction of SAMP with albumin in a molar ratio of, respectively, 8:1 and 16:1 - were tested in a volunteer and compared to 99mTc-RBCs. The blood time-activity curves of the three preparations were quite similar but both 99mTc-DMP-HSA preparations were excreted much less into the urine than 99mTc-RBCs. Ventriculography was performed with the three tracer agents, each time with a 1-week interval. In the three studies, the heart was clearly visualized and the left and right ventricle could be easily delineated. The ejection fractions obtained after administration of the three preparations were similar. With both 99mTc-DMP-HSA preparations the low activity in the spleen was a distinct advantage and facilitated delineation of the left ventricle.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7995284 TI - Evaluation of technetium-99m exametazime stabilised with cobalt chloride as a blood flow tracer in focal cerebral ischaemia. AB - A protocol has been devised to effectively extend the limited post-reconstitution shelf life of technetium-99m exametazime as a radiopharmaceutical for imaging cerebral blood flow (CBF) distribution. The potential of 99mTc-exametazime stabilised with cobalt chloride for imaging CBF distribution as late as 4 h after reconstitution has been examined in ischaemic and non-ischaemic tissue in halothane-anaesthetised cats. Focal cerebral ischaemia was produced by permanent middle cerebral artery occlusion. The relationship between 99mTc-exametazime uptake and retention and CBF (assessed with [14C]iodoantipyrine 10 min after first radiopharmaceutical administration) was determined in the same tissue section with double label autoradiography. Over the CBF range 0-80 ml 100 g-1 min 1, the uptake of 99mTc-exametazime (quantitatively and topographically) was linearly related to CBF irrespective of whether the 99mTc-labelled tracer was unstabilised (and administered within 10 min of reconstitution) or was stabilised with cobalt chloride (and administered up to 240 min after reconstitution). For levels of CBF in excess of 80 ml 100 g-1 min-1 the excellent topographical relationship between 99mTc-exametazime distribution and CBF is maintained but quantitatively, 99mTc-exametazime underestimates CBF to a similar degree in animals receiving stabilised and unstabilised 99mTc-exametazime. The presence of the stabiliser, cobalt chloride, extends greatly the period over which 99mTc exametazime can be used after reconstitution to generate images of CBF distribution in normal and ischaemic cerebral tissue. PMID- 7995285 TI - Effect of interleukin-2 on the biodistribution of technetium-99m-labelled anti CEA monoclonal antibody in mice bearing human tumour xenografts. AB - We have evaluated whether interleukin-2 (IL-2) at low doses can enhance delivery of radionuclides to tumour sites by improving the access of the radio-labelled antibody. The effects of 1000 or 2000 units of IL-2 on the biodistribution of technetium-99m-labelled anticarcinoembryonic antigen (CEA) monoclonal antibody, ZCE025, in athymic mice bearing human CEA-positive tumour (MKN45) xenografts were investigated. Treatment with IL-2 resulted in a significantly higher tumour uptake (1.2-1.5-fold) compared with the control group. Some normal organs, such as heart, lung, liver, spleen and kidneys, showed increased 99mTc uptake following the IL-2 treatment. Pretreatment with IL-2 also induced an enhancement of the permeability index for mouse IgG in tumours and in normal organs, whereas the blood flow in both normal organs and tumours remained at control levels. The effects of IL-2 were found to be dose-dependent. The IL-2 treatment increased the plasma CEA levels but not the CEA content in tumour tissues, suggesting that IL-2 enhanced the leakage of CEA from tumour to blood. The enhancement ratios of the tumour 99mTc-ZCE025 uptake following treatment with IL-2 were 1.4 and 1.8 in mice bearing small and large tumours, respectively. Our experimental results indicated that the low dose of IL-2 enhanced the vascular permeability sufficiently to increase the amount of antibody delivered to the tumour target. Administration of IL-2 would render radioimmunotherapy more effective, especially in patients with large tumour burdens. PMID- 7995286 TI - Improved iterative image reconstruction using variable projection binning and abbreviated convolution. AB - Noise propagation in iterative reconstruction can be reduced by exact data projection. This can be done by area-weighted projection using the convolution method. Large arrays have to be convolved in order to achieve satisfactory image quality. Two procedures are described which improve the convolution method used so far. Variable binning helps to reduce the size of the convolution arrays without loss of image quality. Computation time is further reduced by abbreviated convolution. The effects of the procedures are illustrated by means of phantom measurements. PMID- 7995287 TI - Multicompartmental study of fluorine-18 altanserin binding to brain 5HT2 receptors in humans using positron emission tomography. AB - Serotoninergic type 2 (5HT2) receptors have been implicated in the regulation of many brain functions in humans and may play a role in several neurological and psychiatric diseases. Fluorine-18 altanserin has been proposed as a new radiotracer for the study of 5HT2 receptors by PET because of its high affinity for 5HT2 receptors (Ki: 0.13 nM) and its good specificity in in vitro studies. Dynamic PET studies were carried out in 12 healthy volunteers after intravenous injection of 0.1 mCi/kg [18F]altanserin. Ninety minutes after injection, we observed mainly cortical binding. Basal ganglia and cerebellum showed very low uptake and the frontal cortex to cerebellum ratio was about 3. To evaluate the quantitative distribution of this ligand in the brain, we used two different methods of data analysis: a four-compartment model was used to achieve quantitative evaluation of rate constants (K1 and k2 through k6) by non-linear regression, and a multiple-time graphical analysis technique for reversible binding was employed for the measurement of k1/k2 and k3/k4 ratios. Using both methods, we found significant differences in binding capacity (estimated by k3/k4 = Bmax/Kd) between regions, the values increasing as follows: occipital, limbic, parietal, frontal and temporal cortex. After correction of values obtained by the graphical method for the existence of non-specific binding, results generated by the two methods were consistent. PMID- 7995288 TI - Pinhole skeletal scintigraphic manifestations of Tietze's disease. AB - Tietze's disease (TD) is a self-limited, non-specific, inflammatory condition of the upper costochondral junction (CCJ). Unlike in many other skeletal diseases, radiography plays a relatively minor role in TD because radiographic changes are frequently obscured by physiological costochondral calcifications. Bone scanning is a sensitive test for TD, but its specificity is low. The present study has been conducted to assess prospectively whether pinhole scintigraphy (PS) can enhance diagnostic specificity in TD. Both planar and PS bone images were obtained in seven ribs of five patients with TD. Scans alterations were analyzed and compared with the radiographic findings. Planar scans showed "hot" areas in the region of the CCJ in all seven ribs, these hot areas lacking textural patterns. However, the magnified PS images of the CCJ showed two characteristic uptake patterns: drumstick-like uptake in acute cases and C- or inverted C-shaped uptake in chronic cases. Radiographically, chondritic sclerosis could be seen when physiological chondral calcifications were minimal or absent, but was observed when the calcification was prominent. The correlation of PS and radiographic findings revealed that C- or inverted C-shaped uptake indeed faithfully reflected the inflammatory process in the CCJ, the medial border of which is concave. The further correlation of magnetic resonance and PS images of two lesions in one patient in whom histological examination was performed showed that C- or inverted C-shaped uptake is closely associated with hypervascularity of TD. Differential diagnosis between TD, fracture and metastasis is discussed. PMID- 7995289 TI - Lung mucociliary clearance. AB - The aim of this study was to establish reference values for mucociliary clearance and mucociliary clearance reserve capacity as determined by beta 2-adrenergic agonist-induced increase in mucociliary clearance. We studied 62 healthy females (n = 33) and males (n = 29). Their ages ranged evenly between 18 and 84 years. Fifty-three of the subjects were life-long non-smokers, while nine were ex smokers. Multiple linear regression analyses showed that mucociliary clearance was significantly faster when the radioaerosol was deposited in the central airways than when it was deposited in the peripheral airways, and faster in life long non-smokers than in ex-smokers. There was no influence of age, and no convincing association with sex. The variation was less within than between subjects. Mean mucociliary clearance reserve capacity was 21.3% (SD: 10.0%, P < 0.0001). The beta 2 agonist-induced increase in lung mucociliary clearance was significantly larger (P < 0.05) than the stimulation which has previously been reported in patients with asthma, bronchiectasis or cystic fibrosis. The signal to-noise ratio of the mucociliary clearance reserve capacity in relation to measurement of baseline mucociliary clearance indicates that measurement of mucociliary clearance reserve capacity may be a more efficient means of distinguishing between "normal" and "abnormal" mucociliary clearance than single measurement of baseline mucociliary clearance. PMID- 7995290 TI - Scintigraphic findings of the thyroid in hypothyroid patients with blocking-type TSH-receptor antibodies. AB - The present study was designed to analyse the scintigraphic appearance of the thyroid in hypothyroid patients with blocking-type TSH receptor antibodies (TRAbs). Eleven hypothyroid patients with autoimmune thyroiditis positive for TSH binding inhibitor immunoglobulins (TBII) [80% +/- 12 (SD)%; normal < 11%] and for thyroid stimulation-blocking antibodies (TSBAbs) (90% +/- 9%: normal < 32%) were studied. Thyroid scanning was performed using technetium-99m or iodine-123, when the patients were hypothyroid. Analysis of the scan images revealed the presence of localized functioning areas in six patients (group 1), and no visualization of the thyroid in the remaining five patients (group 2). Patients in group 1 showed significantly higher uptake of 99mTc than those in group 2 (P < 0.05). Interestingly, three patients in group 1 were positive for thyroid-stimulating antibodies (TSAbs) (249% +/- 17%; normal < 145%), which were not detected in the remaining eight patients. Antibodies against thyroglobulin and microsomal antigens were detected in nine nine (81.8%) and 11 (100%) patients, respectively, but neither of these titres correlated with the scan image. Three patients in group 1 underwent scintigraphy again after treatment with thyroxine, at which time the functioning lesion was not noted. Fourteen hypothyroid patients with negative TBII displayed no such scintigraphic findings. Chronic stimulation of the thyroid by TSAbs and/or TSH might be responsible for the presence of the functioning lesion, but clarification of the mechanism requires further studies. In summary (1) TSAbs were detected in three (27.3%) of 11 hypothyroid patients with blocking TRAbs; (2) thyroid scintigraphy revealed the presence of localized functioning area(s) in approximately half of these cases. PMID- 7995291 TI - Patency of the infarct-related coronary artery--a pertinent factor in late recovery of myocardial fatty acid metabolism among patients receiving thrombolytic therapy? AB - The decrease in mortality among patients receiving thrombolytic therapy for myocardial infarction is greater than would be expected from the improvement in left ventricular contractile function alone; thus some additional advantage of recanalization of the infarct-related coronary artery probably exists. Changes in the post-infarction myocardial metabolic state with respect to artery patency have not been studied with a gamma camera previously. A single-photon emission tomography scan using the fatty acid analogue para-123I-iodophenylpentadecanoic acid was performed at rest before hospital discharge on nine patients with first anterior myocardial infarction. All patients had received intravenous thrombolytic therapy at the beginning of the insult. The semiquantitative analysis of the left ventricle included a total of 44 segments in each patient. The test was repeated 3 months later, with the patients divided into two groups: six patients had an angiographically patent left anterior descending coronary artery (group A), and three an occluded artery (group B). In group A the number of myocardial segments with abnormal (< 70% of maximum) fatty acid uptake was initially 20.2 +/- 4.7 (mean +/- SD) and was reduced to 11.3 +/- 6.1 during the follow-up (95% confidence interval of the decrease 16.0-1.7 segments). In group B the number of these aberrant segments was fairly constant (21.7 +/- 13.1, initial test, and 21.3 +/- 13.3, retest). Our preliminary results suggest that even when thrombolytic therapy fails to prevent myocardial infarction, myocardial fatty acid metabolism has a better change of recovering if the relevant coronary artery has regained its patency.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7995292 TI - Assessment of tumour necrosis and detection of mediastinal lymph node metastasis in bronchial carcinoma with technetium-99m sestamibi imaging: comparison with CT scan. AB - Thirty-eight patients with four major types of bronchial carcinoma were studied to evaluate technetium-99m sestamibi imaging in the assessment of tumour necrosis and the detection of hilar and mediastinal lymph node metastasis. Quantitative analysis was also performed to ascertain whether tumour uptake values correlate with histological types of bronchial carcinoma. Of the patients, 34 showed tumour uptake on planar imaging (n = 38) and 27 on single-photon emission tomography (SPET) (n = 29), the overall sensitivity in the localisation of primary tumour being 89% with planar imaging and 93% with SPET. Four types of tumour uptake pattern were identified: (1) focal uptake, (2) focal uptake with a central hypoactive focus. (3) ring-like uptake and (4) no uptake (negative uptake). Tumour necrosis was diagnosed in 12 patients based upon histopathology (n = 2) and density measurements and type of contrast enhancement on computed tomography (CT) scan (n = 12). Defective tumour uptake was seen in 11 of these patients on planar images (focal uptake with a central hypoactive focus, n = 7; ring-like uptake, n = 2; and no tumour uptake, n = 2) and in 12 patients on SPET (focal uptake with a central hypoactive focus, n = 7, ring-like uptake, n = 3, and no uptake, n = 2). Hilar and mediastinal lymph node involvement was detected in ten patients on CT scan, nine on planar images and 11 on SPET. A total of 26 metastatic lymph nodes were detected on CT scan: 24 of these were seen on planar, and all 26 on SPET images.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7995293 TI - The role of technetium-99m sestamibi whole-body scans in diagnosing metastatic Hurthle cell carcinoma of the thyroid gland after total thyroidectomy: a comparison with iodine-131 and thallium-201 whole-body scans. AB - Thirty-seven patients with Hurthle cell carcinoma of the thyroid gland underwent total thyroidectomy and then technetium-99m sestamibi (2-methoxy isobutylisonitrile), iodine-131 and thallium-201 whole-body scans. Twenty-two of them had elevated human serum thyroglobulin (HTg) levels. Among these 22 patients, abnormal uptake of 131I was seen in four (18.1%), abnormal uptake of 201Tl chloride in 15 (68.1%), and abnormal 99mTc-sestamibi accumulation in 18 (81.8%). No patients with normal levels had a positive whole-body scan. In comparison with the 131I and 201Tl chloride images, the 99mTc-sestamibi images were of superior quality and detected significantly more (P < 0.05) metastatic lesions of Hurthle cell carcinoma of the thyroid gland in patients with elevated HTg after total thyroidectomy. A mechanism is proposed that may explain these findings. PMID- 7995294 TI - Gall-bladder and colonic retention of SeHCAT: a re-evaluation. AB - A number of suggested alternatives and emendations to the 7-day SeHCAT retention test have been compared with whole-body counting. It was found that correction for colonic retention is an unnecessary complication in patients with diarrhoea and that imaging either of the gall-bladder or of the distribution of activity in the intestines at 24 h does not add useful information to the standard 7-day retention measurement. Neither could the patterns of colonic uptake identified in patients following extensive ideal resection or radiotherapy be reproduced in patients with idiopathic diarrhoea. Sadly it must be concluded that neither of these shortened techniques is of clinical value in patients with intact small bowel and that there remains no reliable alternative to the 7-day Se HCAT retention test. The simplest technique the best. PMID- 7995295 TI - Formulation of a single-component kit for the preparation of technetium-99m labelled ethyl cysteinate dimer: biological and clinical evaluation. AB - Ethyl cysteinate dimer (ECD) labelled with reduced technetium-99m has recently been proposed as a promising radiopharmaceutical for brain perfusion imaging. In the present study a single-component kit formulation has been developed, thus simplifying the radiolabelling procedure. A method of analysis by electrophoresis has also been developed, permitting identification of radiochemical impurities in the preparation. 99mTc-ECD prepared by the single-component kit was further evaluated in primates and humans. The results demonstrated that the complex is stable in vivo, rapidly extracted and retained in the brain tissue for a sufficient time for single-photon emission tomography studies. Therefore the present single-component kit formulation can be proposed as a reliable instant freeze-dried kit for routine preparation of 99mTc-ECD required for scintigraphic assessment of regional cerebral blood flow. PMID- 7995296 TI - Carcinogenic risk in diagnostic nuclear medicine: biological and epidemiological considerations. AB - During the last decade new data have become available on the mechanism of carcinogenesis and on cancer induction by ionizing radiation. This review concentrates on these two items in relation to the use of radiopharmaceuticals in diagnostic nuclear medicine. On the basis of reports of expert committees, the concept of radiation risk is elucidated for high and low doses. Mortality risk factors due to ionizing radiation are put in perspective to other risks. The extra risk for patients who undergo a scintigraphic examination for fatal cancer is very small and is of the order of 1.4 x 10(-4). It is most unlikely that this figure can even be verified by actual measurement since the majority of nuclear medicine patients will die of other causes before the radiogenic cancer manifests itself. PMID- 7995297 TI - Gene therapy in neurology. PMID- 7995298 TI - MRI volumetry of medial temporal lobe structures in amnesia following herpes simplex encephalitis. AB - Using a magnetic resonance imaging-based volumetry, we quantified the volumes of the hippocampal formation (HF), parahippocampal gyrus (PHG), amygdaloid body (AMB), and anterior temporal neocortex (ATN) in 5 post-herpes simplex encephalitic (post-HSE) patients with temporal lobe damage and memory impairment at 12-52 months after the onset, and in 10 age-matched control subjects. In the post-HSE patients, the HF (p < 0.001) and PHG (p < 0.005) were significantly atrophic, while the AMB (p = 0.155) and ATN (p = 0.102) were smaller but not significantly. Performances on the verbal learning memory tests correlated highly with the HF volume, and length of dense retrograde amnesia with the PHG atrophy. Two patients with severe lasting amnesia had a marked atrophy of the HF and PHG, while 3 patients with good recovery from initial amnesia had temporal lobe structures larger than 50% of the control mean volumes. These results suggest that anterograde and retrograde memory functions involve different neural structures; the former is related to the HF and the latter to the PHG. For producing lasting amnesia, either severe HF damage or a combined damage of the HF and PHG might be necessary. PMID- 7995299 TI - Neuropathology of late cortical cerebellar atrophy in Japan: distribution of cerebellar change on an autopsy case and review of Japanese cases. AB - We report a Japanese autopsy case of late cortical cerebellar atrophy. The patient had showed clinically transient remission during thyrotropin-releasing hormone therapy. Our case suggests that thyrotropin-releasing hormone therapy is worth trying as a treatment of late cortical cerebellar atrophy. Neuropathological examination showed diffuse cerebellar cortical lesions and absence of neuronal loss in the dorsomedial part of the inferior olives. We studied qualitatively the detailed distribution of the cerebellar cortical lesions in 6 sections of the right cerebellum. The cerebellar lesions were more conspicuous in the most lateral hemisphere than in the vermis. We also reviewed 7 Japanese autopsy cases of late cortical cerebellar atrophy. PMID- 7995300 TI - Unaltered respiratory chain enzyme activity and mitochondrial DNA in skeletal muscle from patients with idiopathic Parkinson's syndrome. AB - There is good evidence that patients with Parkinson's disease have respiratory chain dysfunction in their substantia nigra. Since mitochondrial cytopathies due to enzyme defects in the respiratory chain are predominantly manifested in tissues with a high oxidative metabolism we analyzed oxidative energy metabolism in skeletal muscle from 6 patients with Parkinson's disease. Control muscles were from subjects of the same age group. Histological and histochemical analyses showed no morphological abnormalities found in mitochondrial myopathies. Biochemical analyses of the various complexes of the respiratory chain were normal. Since 13 subunits of complexes I, III, IV and V of the respiratory chain are encoded by the mitochondrial genome we performed Southern blot and PCR analyses in skeletal muscle from patients and controls and found no disease specific increase in deletions or insertions of the mitochondrial genome. Therefore, we do not think that skeletal muscle reflects the mitochondrial disturbance in Parkinson's disease found in the substantia nigra. PMID- 7995301 TI - Pattern reversal visual evoked potentials in minor head injury. AB - Pattern reversal visual evoked potentials (PR-VEPs) have been recorded in 50 patients with minor head injury (MHI) on days 1 and 30 after trauma and the data compared to 20 normals. None of the patients had visual complaints. The aim was to investigate a possible visual pathway affection in MHI and test the usefulness of PR-VEPs as an objective noninvasive tool in the detection of a possible subclinical affection of the visual system in MHI. P100 latency and amplitude had no significant difference compared to normals. Comparison of patient data on days 1 and 30 after trauma showed a significant latency decrease and amplitude increase on day 30, compared to day 1. These alterations were not age dependent. Our data suggest affection of the human visual pathway in MHI. PR-VEP recording seems to be a useful, objective, noninvasive tool, helping to identify possible subclinical affections of the visual pathway in MHI. PMID- 7995302 TI - Cognitive functions in subjects with incidental cerebral hyperintensities. AB - We investigated the association between incidental cerebral hyperintensities (CH) found by magnetic resonance imaging (MRI) and cognitive functions in neurologically normal, nondemented subjects. Semiquantitative scores for MRI lesions and those for brain atrophy were compared with the results of extensive cognitive examinations using multivariate analysis. There was no correlation between CH and cognition, except that periventricular hyperintensities, especially those in posterior locations, were associated with reduced performance in the Stroop test. Overall cognitive functions were associated with age, and age was a predominant factor in the prefrontal functions. Brain atrophy was associated more with decline of the posterior and dorsolateral frontal brain functions. We suggest that disturbances in attention and speed may initially result from incidental CH, while other cognitive functions remain unaffected. PMID- 7995303 TI - Awareness of cognitive deficits and anosognosia in probable Alzheimer's disease. AB - We examined the relationship between unawareness of cognitive deficits and psychiatric and neuropsychological manifestations in 181 patients with probable Alzheimer's disease (AD). Patients unaware of their cognitive deficits were more cognitively impaired, as measured by the Mini-Mental State Examination, and had a specific defect in 'frontal/executive' functions. The presence of major depression, delusions and hallucinations was no more likely among patients who were aware of their cognitive impairment than among those who were not. These findings have important implications for the understanding of anosognosia and deficit awareness in dementia. PMID- 7995304 TI - Conduction block in vasculitic neuropathy. AB - We describe a 28-year-old man who developed a mononeuropathy with a conduction block of the median nerve in the forearm, during the acute stage of a polyarteritis nodosa. Sequential studies show progressive disappearance of the conduction block (together with the clinical symptoms), without signs of axonotmesis. PMID- 7995306 TI - Catecholamine syndrome, carcinoid lung tumor and stroke. PMID- 7995307 TI - Atraumatic temporal lobe pathology and autobiographical memory. PMID- 7995305 TI - Cheiro-oral syndrome with internuclear ophthalmoplegia and cerebellar ataxia following midbrain infarction. PMID- 7995308 TI - Cognitive improvement following treatment in a case of idiopathic hypoparathyroidism. PMID- 7995309 TI - Hemiplegia in pregnancy due to metastatic cerebral angiosarcoma. PMID- 7995310 TI - Sensory perineuritis and non-Hodgkin's T-cell lymphoma. PMID- 7995311 TI - Rotation-induced change of muscle tone. PMID- 7995312 TI - A comparison of lisinopril and nifedipine in the treatment of mild to moderate hypertension. A multicentre study. AB - Lisinopril has been compared with slow-release nifedipine in a 16-week double blind, randomized, parallel-group study involving 102 patients with mild to moderate hypertension. Sitting systolic and diastolic blood pressures were reduced 6 and 5 mmHg more by lisinopril than by nifedipine over 12 weeks monotherapy. After 12 weeks a greater proportion of patients taking lisinopril was controlled (sitting diastolic blood pressure below 95 mm Hg) than in those taking nifedipine. As a result, 17% of those taking lisinopril and 38% of those taking nifedipine required additional therapy with hydrochlorothiazide. The addition of hydrochlorothiazide resulted in similar response rates in the lisinopril and nifedipine groups (89% and 75% respectively). The rate of reporting of adverse events considered to be drug-related and the rate of withdrawals were similar for both treatments. Cough was more often reported with lisinopril and headache, sweating, and hot flushes with nifedipine. We conclude that once-daily titrated doses of lisinopril produced better control of blood pressure than twice-daily titrated doses of nifedipine. PMID- 7995314 TI - Terminology in prescription-event monitoring. AB - The terminology used in prescription-event monitoring for postmarketing surveillance is described. It has been developed by the Drug Safety Research Unit while processing records of 500,000 events associated with the use of new chemical entities by 460,000 patients in England since 1981. Currently, the events are arranged in 24 classes which include 108 high-level terms and 1197 low level terms. Low-level terms are used to code individual events reported by general practitioners, usually without an opinion about any possible causal relationship with a particular drug. Some low-level terms are lumped together as one high-level term when the event rates are estimated. PMID- 7995313 TI - Use of codeine analgesics in a general population. A Norwegian study of moderately strong analgesics. AB - The prescribing of controlled analgesics (codeine, buprenorphine and pentazocine preparations) was studied, using prescriptions from the three pharmacies in the municipality of Tromso, Norway. All prescriptions dispensed during one year were analysed. The study sample comprised 3083 women (58%) and 2223 men (42%) between 10 and 99 years of age. About 8% of the population had obtained one or more prescriptions of controlled analgesics. Combined codeine preparations were by far the most frequently prescribed subgroups, and the average amount purchased during 1 year was 30 defined daily doses (DDD). The sporadic users were in the majority. A few users had purchased high amounts of controlled analgesics. The prevalence of use, the mean number of defined daily doses of analgesics, and the proportion of 'weekly' drug users was higher in women than men. The prevalence increased significantly with age, from 0.7 to 22.3% in women and from 0.5 to 14.1% in men. The mean number of DDD during one year also increased with age, from 12.6 to 50.6 DDD in women, and from 6.6 to 40.6 DDD in men. The users of buprenorphine and pentazocine differed in several aspects from the codeine users. The highest use of combined codeine preparations was seen in elderly people especially in women. Use of lower codeine doses or intermittent treatment with other drugs e.g. plain paracetamol in adequate doses, may be appropriate alternatives reducing the risk of adverse drug reactions such as nausea and constipation. Monitoring of prescribing and use of controlled analgesics according to certain criteria may uncover possible misuse. PMID- 7995315 TI - The effect of industry-independent drug information on the prescribing of benzodiazepines in general practice. AB - In order to measure the effect of industry-independent information on the prescribing of benzodiazepines in general practice, 128 primary practitioners were randomly allocated to three intervention groups after stratification by year of graduation. One third of the participating physicians were forwarded written information about the indications and limitations of benzodiazepines, another third received both written and oral information, and the remaining third (the control group) obtained no information at all. A comparison of the number of benzodiazepines prescribed per 100 patient contacts with prescription before and after the intervention showed an average decrease of 3% in the control group, of 14% in physicians who received only written information, and of 24% in physicians who were given additional oral information. Post hoc pair-wise comparisons revealed a significant difference at the 1% level in the number of benzodiazepines prescribed between physicians who received both written and oral information and the control group. A follow-up survey conducted 4 weeks after the intervention showed that the oral information campaign positively affected physicians' attitudes about the value of oral drug information from an industry independent source. PMID- 7995316 TI - The effects of transdermal scopolamine on autonomic nervous activity during sleep. AB - We studied the effect of transdermally applied scopolamine (scopolamine-TTS) on autonomic nervous activity during sleep. The double-blind, randomized, crossover study was carried out in six healthy male volunteers by applying 1.5 mg scopolamine-TTS or placebo patch on the retroauricular skin and by monitoring heart rate, cardiac ballistogram, respiration and body movements by using electrocardiogram and static charge sensitive bed. Scopolamine did not decrease the time the subjects desired to sleep (516 min after TTS, 511 min after placebo) or the number of body movements of 3-5 s duration the subjects spontaneously performed during sleep (47 after TTS, 58 after placebo). No adverse effects of scopolamine were reported spontaneously. Scopolamine-TTS slowed the mean heart rate during quiet sleep from 53.2 to 44.9 beats.min-1, and increased the duration of bradycardia in response to body movements (MIB-reflex) from 12.5 to 14.7 s with a significant difference between scopolamine and placebo effects. The bradycardias were not associated with disturbances in cardiorespiratory or central nervous system functions. The cardiac vagomimetic action of scopolamine TTS could be explained by low plasma drug concentrations (175 pg/ml) primarily blocking only neuronal inhibitory prejunctional muscarinic receptors which regulate acetylcholine release from the autonomic ganglia and parasympathetic nerve-endings. Because of the central role of acetylcholine in the physiological regulation of sleep, the effect of scopolamine-TTS on sleep merits further investigations. PMID- 7995317 TI - Extrapulmonary beta 2-responses to intravenous salbutamol during the menstrual cycle. AB - Extrapulmonary beta 2-adrenoceptor mediated responses to salbutamol were evaluated in 9 healthy female subjects during the follicular (day 2-4, Visit 1) and luteal (day 21-23, Visit 2) phases of the menstrual cycle, and were compared with those of 9 age-matched male controls. At each visit, salbutamol was given by intravenous infusion for 30 minutes at a dose of 0.2 mg.kg-1.min-1. Plasma salbutamol concentration and responses in heart rate (HR), finger tremor (Tr), Q T interval (Q-Tc), serum potassium (K), serum insulin (Ins) and serum glucose (Glu) were measured at baseline and at 10, 20 and 30 minutes after commencing the infusion. Comparisons were made between sexes and between visits for peak responses calculated as percentage change from baseline. Mean plasma salbutamol concentration (ng.ml-1) were not significantly different between males and females on Visit 1: 6.9 (95% CI 6.01, 7.82) vs 7.3 (95% CI 6.4, 8.3), or on Visit 2: 6.9 (95% CI 6.0, 7.8) vs 7.2 (95% CI 6.3, 8.1). On Visit 1, significantly greater responses were demonstrated in females, compared with males for K (as mean difference): 6 (95% CI 1, 11)%, Tr: 17 (95% CI 1, 33)%, Q-Tc: 8 (95% CI 2, 14)% and Ins: 276 (95% CI 71, 481)%. In addition, a significantly greater response was demonstrated in females on Visit 1 compared with males on Visit 2 for HR (as mean difference): 32 (95% CI 1, 63)%, and for Ins: 262 (95% CI 57, 467)%. Thus, despite no difference in plasma salbutamol concentrations, female subjects exhibited greater responsiveness to salbutamol compared with males during the follicular phase of the menstrual cycle. This suggests that in vivo, females have enhanced sensitivity of extrapulmonary beta 2-adrenoceptors. PMID- 7995318 TI - The effectiveness of topically applied capsaicin. A meta-analysis. AB - To undertake a quantitative overview of trials of topical capsaicin for the treatment of diabetic neuropathy, osteoarthritis, post-herpetic neuralgia, and psoriasis. A systematic search of the literature using both computerized and manual methods for identifying clinical trials of capsaicin. The trials identified were abstracted for response data, which then were analysed using established meta-analytic methods for both fixed and random effects modelling. The odds ratio of the response rate of subjects receiving topical capsaicin relative to that of subjects on placebo was used as the main outcome measure. The difference in the response rate was used as the response variable under the random effects model. When dropouts were mentioned and unambiguous assignment could not be made, the analysis was made on the basis of intention to treat. Capsaicin cream give more pain relief to patients with diabetic neuropathy than placebo did. The odds ratio (OR) and corresponding 95% confidence interval (95% CI) in favour of capsaicin cream were OR = 2.74 (95% CI = 1.73, 4.32). Using a random effect model the rate difference (RD) in favour of capsaicin cream was RD = 0.25 (95% CI = 0.15, 0.35). Capsaicin cream was also better than placebo in providing pain relief in osteoarthritis: OR = 4.36 (95% CI = 2.77, 6.88) and RD = 0.29 (95% CI = 0.20, 0.37) and in psoriasis: OR = 2.80 (95% CI = 1.69, 4.62) and RD = 0.35 (95% CI = 0.14, 0.56). There was, however, evidence of heterogeneity in the individual RDs in psoriasis, and complete binding was difficulty because of the initial discomfort associated with topical capsaicin.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7995319 TI - Smoking and body weight influence the clearance of chlorpromazine. AB - The population pharmacokinetic parameters of chlorpromazine (CPZ) in chronic schizophrenic patients were evaluated using 189 plasma concentration measurements from 31 patients. A NONMEM analysis demonstrated that the clearance of CPZ depended on the patient's body weight. Cigarette smoking and cannabis smoking increased the clearance of CPZ. Chronic alcohol consumption and the concurrent use of anticholinergics did not appear to influence the clearance of CPZ significantly. PMID- 7995320 TI - Recovery cycle of the Hoffmann reflex of tobacco smokers and nonsmokers: relationship to plasma nicotine and cotinine levels. AB - Ten normal adult tobacco smokers and 10 nonsmoking volunteers 20-31 years of age were the subjects of this study. The tobacco smokers all had a history of daily tobacco smoking. They were asked to stop smoking for 12 hours prior to testing. The Hoffmann (H) reflex and its recovery cycle were measured on different days before and just after smoking one nonfiltered 0 mg, low (0.27 mg), or high (2.16 mg) nicotine containing cigarette in a randomized order. Blood samples were drawn immediately after the H reflex recordings in the tobacco smokers. The blood samples were centrifuged, the plasma removed, frozen, and later assayed for nicotine and cotinine levels. Nonsmokers compared to tobacco smokers before smoking only had a tendency for enhanced amplitude of the recovery cycle. After smoking the nicotine containing cigarettes, the tobacco smokers had a depression of the amplitude of the H reflex recovery cycle. The amplitude of the H reflex recovery cycle at 160 ms was reduced. This decreased significantly with increasing plasma nicotine and cotinine concentrations. Individual differences were marked. The data obtained are consistent with evidence in animals that nicotine and tobacco smoke stimulate Renshaw inhibitory neurons in the spinal cord, either directly or indirectly which leads to a skeletal muscle relaxant effect. PMID- 7995321 TI - Salivary nystatin concentrations after administration of an osmotic controlled release tablet and a pastille. AB - Mucosal oral therapeutic system (MOTS) is a controlled-release osmotic system for oral cavity therapy. MOTS (nystatin) is designed to deliver approximately 200,000 units of nystatin over several hours. A crossover study was conducted in five healthy volunteers to evaluate the amount of nystatin released (based on residual drug content) when the system is held in the mouth for 30 min, 1 h, and 2 h, and to compare these concentrations with those achieved with a Mycostatin (nystatin) pastille. An average of 37% of the nystatin content was released intra-orally from MOTS during 2 h in the mouth, which was very similar to the percentage delivered in vitro. Mean salivary drug concentrations were as follows: 279 micrograms.ml-1 at 30 min; 654 micrograms.ml-1 after 1 h; and 532 micrograms.ml-1 at 2 h. These concentrations consistently exceeded those produced by the pastille at the same time points. Fifteen minutes after placement of the pastille in the mouth (i.e., immediately after its dissolution) mean nystatin concentrations reached 746 micrograms.ml-1 but fell rapidly to 13.2 micrograms.ml-1 at 30 min, 7.2 micrograms.ml-1 at 1 h, and 5.6 micrograms.ml-1 at 2 h. The study demonstrates that MOTS maintains high salivary nystatin concentrations throughout a 2 h dosing interval. PMID- 7995322 TI - Pharmacokinetics and pharmacodynamics of lisinopril in advanced renal failure. Consequence of dose adjustment. AB - To prevent drug accumulation and adverse effects the dose of hydrophilic angiotensin-converting enzyme (ACE) inhibitors, e.g. lisinopril, must be reduced in patients with renal failure. To obtain a rational basis for dose recommendations, we undertook a prospective clinical trial. After 15 days of lisinopril treatment pharmacokinetic and pharmacodynamic parameters were determined in patients with advanced renal failure (n = 8; endogenous creatinine clearance [CLCR]: 18 ml.min-1.1.73 m-2) and in healthy subjects with normal renal function (n = 16; CLCR: 107 ml.min-1.1.73 m-2). The volunteers received 10 mg lisinopril once daily, the daily dose in patients (1.1-2.2 mg) was adjusted to the individual CLCR according to the method of Dettli [13]. After 15 days of lisinopril treatment the mean maximal serum concentration (Cmax) in patients was lower than in volunteers (30.7 vs 40.7 ng.ml-1, while the mean area under the concentration-time curve (AUC0-24 h) was higher (525 vs 473 ng.h-1.ml-1). ACE activity on day 15 was almost completely inhibited in both groups. Plasma renin activity, angiotensin I and angiotensin II levels documented marked inhibition of converting enzyme in volunteers and patients. Furthermore, average mean arterial blood pressure in patients decreased by 5 mmHg and proteinuria from 3.9-2.7 g per 24 h after 15 days of treatment with the reduced dose of lisinopril. Adjustment of the dose of lisinopril prevents significant accumulation of the drug in patients with advanced renal failure during chronic therapy. Mean serum levels did not exceed this in subjects with normal renal function receiving a standard dose.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7995323 TI - Pharmacokinetics and pharmacodynamics of ramipril and piretanide administered alone and in combination. AB - The pharmacokinetics and pharmacodynamics of single oral doses of 5 mg ramipril and 6 mg piretanide administered separately and in combination were determined in a single blind, randomised, 3-period cross-over study in 24 healthy male volunteers. The peak plasma concentrations of ramipril and ramiprilat increased slightly (from 11.9 to 14.8 ng/ml, and from 6.39 to 8.96 ng/ml, respectively) as did the area under the plasma concentration-time curve of ramipril (0-4 h) and ramiprilat (0-24 h) (from 15.8 to 19.8 ng.ml-1.h, and from 63.4 to 74.6 ng.ml 1.h, respectively). The urinary excretion of ramiprilat also rose (from 6.82 to 7.73% of dose) following simultaneous treatment with piretanide. These effects were probably due to reduced first-pass metabolism of ramipril/ramiprilat to inactive metabolites. The blood pressure lowering effect, the time course of inhibition of ACE activity in plasma and the concentration-response relationship for the inhibition of plasma ACE activity were not affected by piretanide. The peak plasma concentration of piretanide was somewhat reduced (from 285 to 244 ng/ml) following simultaneous treatment with ramipril. No other pharmacokinetic parameter was affected. Piretanide increased urine flow, and sodium, chloride and potassium excretion, especially during the first 2 hours following administration. These pharmacodynamic parameters were not affected by ramipril. Thus, simultaneous administration of single oral doses of ramipril and piretanide caused modest changes in the peak and average plasma concentrations of both drugs, which did not lead to detectable alterations in the pharmacodynamic parameters measured in healthy volunteers. PMID- 7995324 TI - A pharmacokinetic interaction between roxithromycin and midazolam. AB - The interaction between roxithromycin and midazolam was investigated in a double blind, randomised crossover study of two phases. Ten healthy volunteers were given roxithromycin (300 mg) or placebo once daily for 6 days. On the sixth day they ingested 15 mg midazolam. Plasma samples were collected and psychomotor performance measured for 17 h. Roxithromycin administration significantly increased the area under the plasma midazolam concentration-time curve from 8.3 to 12.2 micrograms.ml-1.min and the elimination half-lives from 1.7 to 2.2 h. In psychomotor performance only minor differences were seen between the treatments in one of the measured psychomotor parameters. Thus, in contrast to the strong interaction between erythromycin and midazolam, the interaction between roxithromycin and midazolam appears less likely to be clinically significant. PMID- 7995325 TI - The effects of single oral doses of 17 beta-oestradiol and progesterone on finger skin circulation in healthy women and in women with primary Raynaud's phenomenon. AB - The effects of sex, the menstrual cycle, oral contraceptives, pregnancy, and the menopause on skin perfusion in healthy women and in patients with Raynaud's phenomenon suggest a role of female sex hormones. However, no clear relation between skin blood flow and circulating concentrations of oestrogens or progestogens has yet been found. The aim of this study was to investigate the effect of orally administered 17 beta-oestradiol and progesterone on finger skin blood flow before and during heat and cold challenge in 17 healthy normotensive women and in 12 women with Raynaud's phenomenon. In each subject standardized finger heating (45 degrees C water bath, 10 min) and cooling tests (15 degrees C water bath, 5 min and 20 min recovery) were performed twice on the second (or third) day of two consecutive menstrual cycles. 17 beta-Oestradiol (9 mg) or progesterone (300 mg) were given before the second test, after a first test with placebo. Both hormonal doses resulted in (high) physiological concentrations. Fingertip skin temperature and laser Doppler flux were measured. There were no significant differences in the test results after placebo and after progesterone. Although values of fingertip skin temperature and laser Doppler flux after 17 beta-oestradiol tended to be higher only the precooling values in the healthy subjects reached significance: fingertip skin temperature respectively with placebo and with oestradiol (mean (SD)): 32.7 (1.0) and 33.1 (0.8) degrees C; laser Doppler flux with placebo and with oestradiol: 33.6 (11.7) and 42.2 (9.5) perfusion units; both P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7995326 TI - Plasma concentrations of the enantiomers of halofantrine and its main metabolite in malaria patients. AB - The plasma concentrations of the enantiomers of halofantrine and its N-desbutyl metabolite in six patients with malaria were measured after oral administration of 3 x 750 mg doses of micronised, racemic halofantrine hydrochloride given at 6 hour intervals. Significant differences were observed between the plasma concentrations of the enantiomers both of halofantrine and its N-monodesbutyl metabolite. AUC(0)84h values were higher for (+)halofantrine (9917 micrograms.ml 1.h) than for (-)-halofantrine (6127 micrograms.ml-1.h). The clinical significance of these observations is not known. The isomers have equipotent activity in vitro but their relative toxicity has not yet been assessed. PMID- 7995327 TI - Protein binding of 2-chloro 2'-deoxyadenosine (cladribine) in healthy subjects and in patients with leukaemia. AB - The plasma protein binding of 2-chloro-2'-deoxyadenosine (CdA) at 37 degrees C was studied by ultrafiltration in 5 healthy volunteers, in 11 patients with haematological malignancies and in purified protein preparations. In the patients, the binding of CdA to plasma proteins was 25.0% and in healthy subjects it was 21.1%. In a solution of human serum albumin (40 g.l-1), 24.3% CdA was bound, but less than 5% was bound in a solution of alpha 1-acid-glycoprotein (0.7 g.l-1). No dependence of binding on the concentration of CdA was found within a range 25-1000 nmol.l-1. In conclusion, due to its limited binding to plasma proteins, any change in the binding of CdA is unlikely to have a major influence on its pharmacological effect. PMID- 7995328 TI - Effect of saliva flow rate on saliva phenytoin concentrations: implications for therapeutic monitoring. AB - The effect of atropine-induced reductions in saliva flow rate on saliva phenytoin concentrations were evaluated in a randomised placebo-controlled crossover study in a group of epileptic patients stabilised on the drug. Pretreatment with atropine caused significant reductions in saliva flow rates during the first 4 h, compared to saline. The AUC0-4 h for saliva flow rate was significantly reduced by atropine (245 g vs 327 g) and the saliva phenytoin AUC0-4 h was significantly increased (5.6 micrograms.ml-1.h vs 4.5 micrograms.ml-1.h) without affecting plasma phenytoin concentrations. The saliva/plasma phenytoin AUC0-4 h ratio was therefore significantly increased by atropine (0.15 vs 0.12). However, there was a poor correlation between saliva/plasma phenytoin concentration ratios and saliva flow rates for the two treatments in the individual patients (correlation coefficient ranged from 0.25 to 0.65). These findings demonstrate that saliva phenytoin concentrations are increased by reductions in saliva flow rate. Caution is therefore required when saliva phenytoin concentrations are used for therapeutic monitoring in the presence of factors which may affect saliva flow rate. PMID- 7995329 TI - The countering of diazoxide-induced vasodilatation by tenoxicam in normal volunteers. AB - The effect of the nonsteroidal anti-inflammatory drug, tenoxicam, on diazoxide induced lowering of standing diastolic blood pressure was explored in 10 normal volunteers. With diazoxide there was a significant fall in the 5-min standing diastolic pressure, i.e. a median drop of 15.5, 11.0, 9.5 and 7.0 mm Hg at 10, 35, 75 and 105 min, respectively, but with the tenoxicam-diazoxide regimen this pressure did not differ significantly from baseline at any time point. Tenoxicam did not modify the diazoxide-induced changes in blood glucose and plasma insulin. It may be that prostaglandins normally contribute to the lowering of peripheral vascular resistance, or that acutely-administered diazoxide enhances the release of vasodilatory prostaglandins. PMID- 7995330 TI - On the relation between standard deviation and arithmetic mean in pharmacokinetic studies. PMID- 7995331 TI - Changes in clearance create pharmacokinetic pitfalls as illustrated by studies on tiopronin. PMID- 7995332 TI - The pharmacokinetics of tiopronin as such is unknown. PMID- 7995333 TI - Placental structure: in a comparative aspect. AB - The outstanding structural diversity of the placenta among mammals, i.e. horse, pig, domestic ruminants, cat. Guinea pig and human, has been studied in a comparative manner using terms of classification such as: type of placental membranes, placental shape, placental maternofetal interdigitation, layers of the placental interhemal barrier, trophoblast invasiveness and decidual cell reaction, formation of syncytiotrophoblast, maternofetal blood flow interrelationships, and placental separation at birth. These terms, originating partly from classical acquirements of knowledge and partly from recent research, are presented and new aspects discussed; thus helping towards a better understanding of the structure and function of the different placental types. PMID- 7995334 TI - The fetoplacental unit of primates. PMID- 7995335 TI - The horse feto-placental unit. AB - In the pregnant mare two different groups of oestrogens are produced by the placenta. The precursor of "classical" oestrogens (oestrone, oestradiol-17 beta and oestradiol-17 alpha) is dehydroepiandrosterone which originates from the fetal gonads. The ring B unsaturated oestrogens (equilin and equilenin and their derivatives) derive from farnesyl pyrophosphate by a pathway not involving cholesterol. PMID- 7995336 TI - Investigations on the use of C-21-steroids as precursors for placental oestrogen synthesis in the cow. AB - Cotyledonary homogenates from 220 and 270 day pregnant and term cows were incubated (NADPH- and NAD(+)-regenerating system) with 3H-pregnenolone and 3H progesterone, respectively. Identification of metabolites was based on separation on HPLC and the respective retention times. On days 220/270 the major metabolite formed after incubation with 3H-pregnenolone was progesterone, followed by 17 alpha-hydroxyprogesterone and dehydroepiandrosterone/17 alpha hydroxypregnenolone; the formation of estrone was low (up to 6%), while it was the major metabolite after incubation of pregnenolone with term placenta. At all stages of pregnancy investigated, the only metabolite found after incubation with 3H-progesterone was 17 alpha-hydroxyprogesterone. These data provide evidence that 17 alpha-hydroxyprogesterone is the endpoint of steroid biosynthesis in the bovine placenta along the delta 4-route and that oestrogen synthesis follows the delta 5-pathway. Based on the high activity of 3 beta hydroxysteroiddehydrogenase/delta 5/4-isomerase also found on days 220/270, the key enzyme allowing for placental oestrogen synthesis in the cow seems to be cytochrome P450c17 alpha. Thus the situation in the cow is similar to that in the sheep and the increased turnover of pregnenolone into estrone may explain the decrease of placental progesterone production in the cow towards the end of gestation. PMID- 7995337 TI - Aspects of placental estrogen synthesis in the pig. AB - Conceptus estrogen synthesis in the pig begins with the d 11 blastocyst and continues throughout pregnancy. Estrogens have been implicated as regulators of numerous in utero events related to conceptus survival and development. Studies conducted in our laboratory indicate that progesterone (P4) production by the porcine placenta increases steadily throughout gestation. Estrone (E1) production is triphasic with peaks between d 14-18, around d 30, and a sustained increase from d 70 until parturition. Addition of pregnenolone (P5) augments in vitro P4 and E1 production by both the placenta and the endometrium. Both estrogen concentrations and the ratio between conjugated and free estrogens change drastically during gestation. Evidence from our laboratory suggests that enhanced and prolonged sulfatase activity by d 90 of gestation, coupled with an increase in sulfatase activity-not a change in aromatase activity-contributes to the rise in free estrogens as parturition approaches. We assessed the relative importance of ovarian versus placental production of P4 as a mediator of prenatal survival, conceptus development, and steroidogenesis by the placenta and endometrium. Among other findings, exogenous administration of the non-aromatizable progestagen medroxyprogesterone acetate (MPA) to ovariectomized (OVX) gilts between either d 20-30 or d 60-70 of gestation did not adversely affect concepts survival or development, in vivo estrogen measurements, or in vitro placental steroidogenesis. We also demonstrated that pregnancy may also be maintained during d 20-30 and d 60-70 in OVX gilts administered large quantities of P5 exogenously, presumably due to placental P4 production. Recent studies have examined variables of region of the placenta and intrauterine position on conceptus development, and placental and endometrial steroidogenesis under normal and crowded intrauterine conditions. Results indicated 1) a differential release of P4 and E1 by different regions of the placenta at certain days of gestation, 2) no compensatory increase in steroidogenic activity of the pig placenta when total placental mass was reduced, and 3) a less pronounced effect of intrauterine position on steroidogenic activity in the pig compared with other litter-bearing species. PMID- 7995338 TI - Investigations on hormonal changes around parturition in the dog and the occurrence of pregnancy-specific non conjugated oestrogens. AB - Concentrations of progesterone and estradiol-17 beta were determined throughout pregnancy in 6 to 10 bitches (exp. 1); in experiment 2 peripartal changes of estradiol-17 beta, estrone, progesterone, cortisol, prolactin and growth hormone were determined in 5 bitches; in experiment 3 total unconjugated oestrogens were determined by radioimmunoassay and radioreceptorassay in placental tissue from 25, 53, 60 and 64 days pregnant bitches. No pregnancy specific increase of estradiol-17 beta could be observed; estradiol-17 beta levels decreased prior to parturition concomitant with the decrease of progesterone, suggesting a likewise luteal origin of estradiol-17 beta in the pregnant and non pregnant dog. Cortisol and growth hormone concentrations were elevated at the time of parturition, prolactin concentrations remained unchanged but were higher in pregnant than in non pregnant dogs. No hints in respect to a specific placental oestrogen production were obtained when examining placental tissue. The hypothesis is put forward that the high sensitivity of the haematopoietic system of the dog to oestrogen was an important factor in respect to evolution of endocrine control of pregnancy and parturition in this species which-in respect to placental oestrogen production-seems to be different from most other domestic animal species. PMID- 7995339 TI - Luteal versus placental progesterone: the situation in the cow, pig and bitch. AB - Placenta and corpus luteum (CL) have acquired different functions for progesterone synthesis and maintenance of pregnancy in the course of placentalia evolution. In the cow and pig, progesterone is produced by the same CL during the entire gestation period with minor or no contribution from the placenta. In the case of an infertile cycle, CL survival is terminated by PGF2 alpha produced by the endometrium. PGF2 alpha secretion is inhibited by the trophoblast in order to guarantee continuous progesterone production. Also in the dog, only the CL synthesizes progesterone and the secretion pattern is similar in pseudopregnant and pregnant animals. The dog CL seems to have an internally programmed life span. PMID- 7995340 TI - Gestagens in peripheral, uterine, ovarian and fetal blood in cows near term. AB - The aim of this study was to determine if bovine placenta is capable of producing the gestagen metabolites in vivo. The concentrations of 5 beta-pregnane-3 alpha 20 alpha-diol, 17 alpha,20 alpha-dihydroxyprogesterone and progesterone were measured by HPLC-RIA in samples obtained after surgical preparation from peripheral, uterine, fetal and ovarian blood of seven cows near term. Measurement of arterio-venous differences in maternal uterine and umbilical circulation confirmed the placental origin of 5 beta-pregnance-3 alpha,20 alpha-diol and 17 alpha,20 alpha-dihydroxyprogesterone, but not progesterone itself. 5 beta pregnane-3 alpha,20 alpha-diol was preferentially secreted into the fetal compartment. The present experiment, according to earlier in-vitro studies, confirms that the preterm bovine placenta is qualified for in-vivo utilization and secretion of gestagen metabolites. PMID- 7995341 TI - Placental progesterone, prostaglandins and mechanisms leading to initiation of parturition in the human. AB - Present knowledge allows the identification of some features of the initiation of human parturition. Progesterone reduces myometrial sensitivity to labour-inducing agents. It suppresses gap junction formation and facilitates beta-adrenergic receptor expression by the myometrium which, in turn, exerts a positive feedback by enhancing beta-adrenergic-induced increases in placental progesterone production. Inhibition of gestagen action does not result in immediate initiation of labor but sensitises myometrial cells to contraction-inducing agents. Estrogens, in contrast, enable the myometrium to prepare for parturition by inducing oxytocin receptors and this seems to be the first step towards parturition. Coordinated myometrial contractions are facilitated by the increased gap junctions due to the estrogen drive. Absence of estrogen will result in failed parturition. The myometrium seems to be sensitised to oxytocin by placental CRF. Myometrial CRF receptors increase their avidity for CRF with ongoing pregnancy. Oxytocin evokes a variety of auto- and paracrine events which culminate in increased free intracellular calcium and the consequent contractions. In this cascade, prostaglandins can be identified as positive feedback agents, as they further enhance estrogen-induced expression of oxytocin receptors. Another second messenger of oxytocin action are the inositol phosphates which can further increase free intracellular calcium concentrations. Finally, endothelin-1, derived from endometrium and decidua, under oxytocin control, may serve as a myometrial contractor following delivery when oxytocin concentrations decline but when a strong myometrial contraction is needed to prevent large blood loss during and after placenta expulsion. PMID- 7995342 TI - Placental progestagens in the sheep and horse and the changes leading to parturition. AB - Placental progestagen production and metabolism during pregnancy, the changes which precede parturition and the extent of fetal involvement in the latter processes are compared in the sheep and the horse. Neither species requires the presence of a corpus luteum for maintenance of the latter part of pregnancy, but the mechanisms involved in placental progesterone/progestagen production are very different in the two species. In sheep the primary product is progesterone (P4), levels of which are high in the maternal but not the fetal circulations. By contrast, in the mare P4 is not detectable in maternal blood after 200 days gestation although it is present in the placenta and fetal circulation. A range of P4 metabolites (primarily 5 alpha-pregnanes) are produced by the equine placenta, while in the fetus pregnenolone and its metabolites are the predominant progestagens. In sheep the prepartum endocrine cascade in which the rise in fetal cortisol stimulates enzyme changes in the placenta so that P4 declines and estrogens and prostaglandins eventually rise, is fairly well established compared with the events preceding delivery in the mare. In the latter species there is a gradual rise in progestagens for 10-20 days before term, at a time when the fetal adrenal is relatively quiescent and unresponsive to ACTH i.e. fetal cortisol levels are low. In the last 24-48 h before delivery maternal progestagens fall, just after fetal plasma cortisol concentrations begin to escalate. The ways in which maternal and fetal prepartum endocrine changes may be interrelated and the possibility of a fetal trigger to parturition in the mare are discussed. PMID- 7995343 TI - Nutritional regulation of uteroplacental prostaglandin production and metabolism in pregnant ewes and mares during late gestation. AB - Prostaglandins (PGs) are produced by a variety of uteroplacental tissues during pregnancy and are released into the fetal fluid sacs and both the uterine and umbilical circulations. Uterine PG output increases towards term and is enhanced by maternal undernutrition in pregnant ewes and mares. In both species, withdrawal of food but not water for 30-48 h increases uterine venous PG levels and the uterine venous arterial concentration differences in PGE and 13, 14, dihydro-15-keto-prostaglandin F2 alpha (PGFM), the stable metabolite of PGF2 alpha. The increments in uterine V-A concentration differences in PGE and PGFM increase towards term and are associated with raised plasma PG levels in the fetal circulation. The PG changes observed during fasting are closely related to the fall in plasma glucose and the rise in plasma FFA in peripheral plasma. When normal metabolite levels are restored either by refeeding or glucose infusion, there is a rapid fall in PG levels with a narrowing of the uterine V-A concentration differences in the ewe and mare. When the data from all the animals are combined, there is an inverse correlation between uterine glucose uptake and PGFM output in both the pregnant ewe and mare. The availability of glucose and FFA to the gravid uterus therefore has an important role in controlling uteroplacental PG production and metabolism in late gestation although the specific steps in biochemical pathways regulated by these metabolites remain unclear. In the ewe, fasting increases uterine contractility and leads to early delivery of viable lambs in animals close to term (> 95% gestation), whereas in the mare it causes premature delivery of non-viable foals in most animals in late gestation (> 80% gestation). Nutritionally induced changes in uteroplacental PG production and metabolism therefore have important consequences for the outcome of pregnancy and may have a pivotal role in the induction of labour both before and at normal term. PMID- 7995344 TI - The primate placenta and human chorionic gonadotropin. AB - In the primate placenta various peptide and proteohormones are synthesized which control growth and development of the fetus as well as the exchange of nutrients and metabolic products between the mother and the fetus. In humans, maintenance of pregnancy in the first trimester depends on the synthesis of the bioactive glycoprotein hormone human chorionic gonadotropin (hCG). It is expressed in placenta by the syncytiothrophoblast of early pregnancy. In cell culture, hCG production seems to mark a certain step in the process of differentiation of cytotrophoblasts and choriocarcinoma cells. It is neither understood how hCG synthesis is initiated and maintained at the beginning of gestation nor what control mechanisms are responsible for the down-regulation of the synthesis at the end of the first trimester. Besides a long list of various other substances which have been described to act as intrinsic placental stimulators of hCG biosynthesis, gonadoliberin and gamma-aminobutyric acid seem to play an important role. This establishes to some extent an analogy to the regulation of gonadotropin synthesis in the central nervous system. Recently, a full-length form of functional LH/hCG receptors of approximately 80 kD has been found in term placenta suggesting autoregulation as a regulatory principle of hCG biosynthesis. In the first trimester placenta as well as in choriocarcinoma cells a truncated form (50 kd) of LH/hCG receptors seems to exist. In these cases, exogenous hCG was unable to down-regulate its own synthesis. The carbohydrate moiety of hCG influences folding, subunit assembly, circulatory half-life, receptor interaction and biological response. A surplus of glycosylation may prevent subunit assembly. Experimental deglycosylation induces a different conformation of hCG, which partly acquires antagonistic properties. Recent results indicate that cAMP, which increases transcription and mRNA stability, also expands the N-glycosylation capacity and thus may accomplish an over-all coordination of hCG biosynthesis including post-translational events. PMID- 7995345 TI - The equine placenta and equine chorionic gonadotrophin--an overview. AB - Chorionic gonadotrophins seem to be unique for primate and equid species. Unlike primates, the equine conceptus does not implant in the maternal uterine endometrium until around day 37 of pregnancy. At this time specialized cells of the trophoblast, organized in the embryonic girdle, invade the endometrium and become established in the endometrial stroma, forming the so-called endometrial cups. This migration of girdle cells is accompanied by their morphological transformation into large decidual-like cells and by the appearance of a gonadotrophic hormone in the mare's blood. There is convincing evidence today that the hormone is of chorionic origin; therefore the term equine Chorionic Gonadotrophin (eCG) seems to be more appropriate than the formerly used term Pregnant Mare Serum Gonadotrophin (PMSG). Secretion of eCG peaks between days 60 and 80 in pregnant mares, to decline gradually until day 130 of gestation, with pronounced inter-individual variation. There appear to be no hormonal regulatory mechanisms controlling eCG synthesis and secretion, suggesting that the size and the morphology of the endometrial cups are the limiting factors. Equine CG is a glycoprotein hormone, composed of noncovalently bound alpha- and beta-subunits. The alpha-subunit consists of 96 amino acids and is identical for eCG and the pituitary hormones eLH, eFSH, and eTSH. The beta-subunit is similar to beta-hCG in that both have a C-terminal extension. It is comprised of 149 amino acids and the peptide primary structure is identical to that of beta-eLH.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7995346 TI - Comparative aspects of placental lactogens: structure and function. AB - Removal of the pituitary from pregnant rats provided early evidence that the placenta was the source of prolactin-like bioactivity. After mid-pregnancy the placenta was able to support progesterone production by the corpus luteum (luteotrophic activity) and continued development of the mammary gland (mammotrophic activity). Three groups of mammals, the rodents, the ruminant artiodactyls and the primates are now known to produce from fetal placenta a remarkable variety of proteins which are related in structure to pituitary prolactin and growth hormone. Prolactin and growth hormone are themselves structurally related and are thought to have arisen from a common ancestral gene by gene duplication and evolutionary divergence. The receptors with which they interact also form a family of homologous proteins. Surprisingly the placental lactogens appear to have arisen more than once in evolution since in primates they are structurally closely related to growth hormone, while in rodents and ruminants they have closer similarity to prolactin. There is suggestive evidence that there may be specific receptors for placental lactogens in some fetal and maternal tissues. In humans a five-gene cluster on chromosome 17 contains two growth hormone (GH) and three placental lactogen (PL) genes. Two human PL genes encode identical proteins that are expressed in the placenta. One of the human GH genes is also placentally expressed. In mice, chromosome 13 carries the genes for mouse prolactin, for placental lactogen-I and -II (PL-I and PL-II) and for two other prolactin-related proteins, the proliferins. Rats also express PL-I and PL II, together with at least three other placental prolactin-like proteins different from proliferins.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7995347 TI - The uteroplacental renin-angiotensin system: a review. AB - Evidence has accumulated for the existence of local tissue renin-angiotensin systems in the reproductive tissues. In the ovary the local renin-angiotensin system (RAS) has been shown to influence ovulation and steroidogenesis. In this review we focus on aspects of a local RAS in the uteroplacental unit. High renin concentrations have been found in all tissues of the uteroplacental unit. The presence of renin mRNA in the endometrium, choriodecidua and the fetal part of the placenta indicates local renin synthesis. Angiotensin (Ang) II, formed by the enzymatic action of tissue renin and Ang I converting enzyme, acts by interaction with its receptors. These receptors have been demonstrated in high densities in the placenta and uterus, indicating an autocrine or paracrine action of Ang II. Several probable effects of the uteroplacental RAS can be defined. It is very likely that the uteroplacental RAS plays an important role during implantation and placentation by stimulation of decidualization and angiogenesis. Furthermore, Ang II may regulate synthesis and secretion of other hormones formed locally in the uteroplacental unit. During labour the action of Ang II may be important for contraction of the uterine musculature, Ang II is also involved in the complex regulation of the uteroplacental blood flow. Species difference in the expression of the uteroplacental RAS exists, and one may speculate that the physiological and pathophysiological roles vary between species. PMID- 7995348 TI - Paracrine and autocrine functions of the placenta: a key to the success of viviparity? AB - The evolution of specific nuclear transcriptional regulators has endowed tissues of the reproductive system with responsiveness to small hydrophobic compounds such as steroids. Steroids are widely distributed in Nature and their distribution in prokaryotes and eukaryotes has given rise to the concept that their hormonal role came about by target organ specialization and not by the evolution of steroids themselves. Specific nuclear receptors for progesterone in the uterus are prominent during the establishment and maintenance of pregnancy. Anti-progesterone antagonists which interfere with receptor-mediated DNA activation abrogate pregnancy and thus emphasize the functional importance of the pathways by which the effects of progesterone as an extracellular signal are transduced. Comparative studies show that progesterone itself can be ovarian or placental in origin. This seems to reflect the evolution of different mechanisms of endocrine function rather than any obvious selective advantage being associated with the source of hormone secretion. For this reason, the question of whether the endocrine function of the placenta is obligatory for the adoption of viviparity in mammals is far from certain, and should be considered as an evolutionary option rather than a sine qua non. Of growing importance is the idea that the interaction between trophoblast and endometrial cells controls the degree of invasiveness at implantation and immunoreactivity.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7995349 TI - Genome fingerprinting of Salmonella typhi by pulsed-field gel electrophoresis for subtyping common phage types. AB - The genomic DNA of 39 strains of Salmonella typhi isolated from local residents and patients who had visited countries in the Asian region was analysed for restriction fragment length polymorphisms (RFLP). Pulsed-field gel electrophoretic (PFGE) analysis of Xba I- and Spe I-generated genomic restriction fragments established 22 PFGE types whereas phage typing differentiated the 39 isolates into 9 distinct phage types. This study showed that PFGE is more discriminatory than phage typing as it is capable of subtyping S. typhi strains of the same phage types. Genetic relatedness among the isolates was determined. Seven major clusters were identified at SABs of > 0.80 and the remaining 13 isolates were distributed into minor clusters which were related at SABs of less than 0.80. In conclusion, PFGE analysis in conjunction with distance matrix analysis served as a useful tool for delineating common S. typhi phage types of diverse origins from different geographical locales and separated in time. PMID- 7995350 TI - Contamination of hands and work surfaces with Salmonella enteritidis PT4 during the preparation of egg dishes. AB - Salmonella enteritidis PT4 was recovered from fingers following the breaking of intact shell eggs artificially contaminated in the contents with the bacterium. Kitchen utensils used to mix egg dishes were salmonella-positive, sometimes after washing. Following the preparation of batter or the mixing of eggs, S. enteritidis was recovered from work surfaces over 40 cm from the mixing bowl. The bacterium survived well in thin, dry films of either batter or egg and, from an initial level of one cell per cm2, could be recovered from formica work surfaces 24 h after contamination. PMID- 7995351 TI - Application of physico-chemical typing methods for the epidemiological analysis of Salmonella enteritidis strains of phage type 25/17. AB - Eighty-nine Salmonella enteritidis phage type 25/17 strains isolated from a localized outbreak in the German state Nordrhein-Westfalen (outbreak NWI) could not be further differentiated by biochemotyping and plasmid pattern analysis. They were submitted to a complex typing system consisting of modern physico chemical analytical procedures. In lipopolysaccharide pattern analysis the strains proved to be homogeneous. In multilocus enzyme electrophoresis, outer membrane and whole cell protein pattern (WCPP) analysis, and Fourier-transform infrared (FT-IR) spectroscopy (increasing extent of differentiation in the given order) strains deviating from each basal pattern were found. The extent of correspondence in these deviations was satisfactory. Forty-six strains of the same sero- and phage type, however, obtained from different outbreaks, were additionally typed. The results obtained with them indicate that the data of the first group were not restricted to strains from outbreak NWI, but of general validity. It was found that both WCPP and FT-IR represent valuable methods for the sub-grouping of bacteria. PMID- 7995352 TI - Changing epidemiology of human salmonellosis in Hong Kong, 1982-93. AB - A comprehensive analysis of the epidemiology of salmonellosis in a major hospital in Hong Kong from 1982-93 is reported. The trend of salmonella isolations over the past 12 years and changes in the occurrence of individual serotypes are delineated. A total of 5328 isolates were analyzed. Groups B (Salmonella typhimurium and S. derby) and E (S. anatum) were the commonest serogroups isolated from the intestinal tract in all age groups. A significant increase in the isolation of group D salmonellae has been observed since 1989. This is accounted for by a substantial rise in S. enteritidis isolation as seen in Western countries, despite a concomitant decrease of S. typhi. The extraintestinal isolation index (EII) is proposed as an index of the virulence potential of individual serotypes and serogroups. Group D salmonella was found to be the most invasive serogroup. While group D was the predominant serogroup isolated from extraintestinal sites in patients older than 1 year, group B serotypes (especially S. typhimurium) were more frequently seen in infants younger than 12 months. PMID- 7995353 TI - Flies and water as reservoirs for bacterial enteropathogens in urban and rural areas in and around Lahore, Pakistan. AB - The study was conducted to isolate and characterize campylobacter, enterotoxigenic Escherichia coli-labile toxin (ETEC-LT), shigella and salmonella in flies and water. The material for the study, flies (n = 300) and water samples (n = 148), was collected from different localities in and around Lahore, Pakistan. Cultivation of the samples was performed on conventional standard media. Membrane filtration technique was used for water prior to culture. Determination of ETEC-LT was done by GM1 ELISA. Results of our study showed that flies and water were reservoirs for all the four pathogens, campylobacter, ETEC LT, shigella and salmonella. Flies from the village were carrying fewer enteropathogens, while water from the village was found to be more contaminated as compared to the city. Campylobacter and ETEC-LT were the most frequently isolated pathogens in both flies and water. Thus the incidence of diarrhoeal disease in children of developing countries may be decreased by providing plenty of safe drinking water, improving excreta disposal, toilet facilities and giving education in personal hygiene. PMID- 7995354 TI - Randomly amplified polymorphic DNA typing: a useful tool for rapid epidemiological typing of Klebsiella pneumoniae. AB - Discriminatory typing methods are invaluable in the investigation of outbreaks of infectious diseases. Single primers were used to generate randomly amplified polymorphic DNA (RAPD) profiles from Klebsiella pneumoniae isolates of various serotype and K. pneumoniae isolates from cases of sepsis at a Malaysian hospital and two English hospitals. RAPD profiles of acceptable reproducibility, a maximum of three minor band variations, were produced using a rapid DNA extraction method. RAPD typing of K. pneumoniae was shown to be as discriminatory as restriction fragment length polymorphism analysis using pulsed field gel electrophoresis yet quicker and less costly. The findings suggest that RAPD typing may be a useful tool for the epidemiological typing of K. pneumoniae. PMID- 7995355 TI - Clonal diversity of Streptococcus pyogenes within some M-types revealed by multilocus enzyme electrophoresis. AB - Twenty-two reference isolates and 30 local isolates of group A Streptococci were classified into 36 electrophoretic types (ET) on the basis of allozyme variation at 27 enzyme loci. Local isolates were characterized by a high frequency of M-non typable strains. M-type and ET were more closely associated in local isolates from an endemically-infected population; nevertheless, amongst the local isolates there were also strains of the same ET type with different M-types. A possible explanation is that genetic exchange between strains may introduce different M types into strains of defined ET when these are exposed to strong selection in the presence of heavy loads of infection. In contrast to the reported clustering of strains associated with toxic shock-like syndrome into two closely related ET clones, we found no relationship of ET phenotype to acute poststreptococcal glomerulonephritis or rheumatic fever. PMID- 7995356 TI - Staphylococcus aureus strains of type 95. Spread of a single clone. AB - Staphylococcus aureus strains of type 95 in Denmark have increased to a frequency of 20% of the total S. aureus population. A clonal origin and possible subdivision of these strains have been discussed. In the present investigation 35 epidemiologically unrelated S. aureus strains of type 95 as well as reference strains of other types have been analysed by other typing techniques including lectin-typing, multilocus enzyme electrophoresis and pulsed-field gel electrophoresis of genomic restriction fragments. No subdivision could be achieved based on any of these methods and a clonal origin seems therefore possible. PMID- 7995357 TI - Duration of carriage and transmission of Yersinia enterocolitica biotype 4, serotype 0:3 in dogs. AB - Human infections with pathogenic strains of Yersinia enterocolitica have been linked to contact with dogs excreting these microorganisms. This study examines the carriage and transmission of Y. enterocolitica biotype 4, serotype 03 in dogs. Fourteen 6-month-old cross-bred dogs were separated into 5 groups, 2 containing 4 dogs (I and II) and the others 2 dogs (III-V). Each of the 4 dogs in Group I and 2 of the dogs in Group II were inoculated orally with the test strain. Bacteriological examination of faecal samples showed that dogs can be readily infected and can carry the organism for up to 23 days. The two in-contact dogs in Group II started to shed the test organism after 5 days. Subsequent transfer of these dogs to Group III and those in Group III to Group IV showed that Y. enterocolitica biotype 4, serotype 03 can be readily transmitted between dogs. At no time did any of the dogs show clinical signs of infection. Group V served as a negative control for the trial. These findings suggest that dogs can carry Y. enterocolitica biotype 4, serotype 03 asymptomatically and hence might act as a potential source of infection for people. PMID- 7995358 TI - Information on which to base assessments of risk from environments contaminated with anthrax spores. AB - Although there has been a considerable amount of research conducted into Bacillus anthracis, the causative agent of anthrax, the data are widely disseminated in the scientific literature and are therefore not always easy to assimilate. In view of continuing concern about potential anthrax contamination in environmental materials and sites, this review brings together the currently available information relating to the health hazards from B. anthracis. The relevance of the available information for risk assessment purposes is assessed. PMID- 7995359 TI - Seroepidemiology of cryptosporidiosis in children in Papua New Guinea and Australia. AB - Enzyme immunoassays (EIA) were used to measure serum antibodies to Cryptosporidium in four immunocompetent adults with recent proven cryptosporidial infection, 379 healthy children and 73 adult volunteers in Melbourne, Australia, and 205 children in Papua New Guinea (PNG) (47 healthy children; 158 with pneumonia). Antibodies peaked 3-6 weeks after infection and fell to baseline within a few months. A high level (5000 EIA units/ml) or a significant change between paired sera, of IgG or IgM, were taken as evidence of recent infection and found in 24% of PNG children and in 8% of children and 5% of adults in Melbourne. Among PNG children with pneumonia who had high cryptosporidial antibody levels, those with measles (6/8) were significantly more likely (P = 0.002) to have diarrhoea than the remainder (4/28). Symptomatic cryptosporidiosis may be associated with transient immune suppression due to viral infection. This study indicates that serological surveys can contribute to an understanding of the epidemiology of cryptosporidosis. PMID- 7995361 TI - The role of the pre-symptomatic food handler in a common source outbreak of food borne SRSV gastroenteritis in a group of hospitals. AB - A common source outbreak of small round structure virus (SRSV) gastroenteritis affected 81 patients and 114 staff in four hospitals served by one central hospital kitchen. Eating salad items was found to be significantly associated with illness. In a cohort study of a staff buffet function eating turkey salad sandwiches was associated with illness (relative risk = 2.4; 95% CI = 1.4-4.1; P = 0.003), and a case control study of patients in one hospital showed an odds ratio of 6.6 (95% CI = 1.0-71.6; P = 0.04) for eating tuna salad and becoming ill. One of two food handlers who prepared the salads became ill the day following food preparation; she also had a young child at home who had been ill with a gastrointestinal illness during the previous two days. Contamination of food by mechanical transmission of the virus from the child via clothes and hands of the mother, or pre-symptomatic faecal excretion in the mother are possible explanations of contamination of food. PMID- 7995360 TI - The epidemiology of bat rabies in New York State, 1988-92. AB - In 1993 New York and Texas each reported a human rabies case traced to a rare variant of rabies virus found in an uncommon species of bat. This study examined the epidemiology of bat rabies in New York State. Demographic, species, and animal-contact information for bats submitted for rabies testing from 1988-92 was analysed. The prevalence of rabies in 6810 bats was 4.6%. Nearly 90% of the 308 rabid bats identified to species were the common big brown bat (Eptesicus fuscus), which comprised 62% of all submissions. Only 25 submissions were silver haired bats (Lasionycterus noctivagans), the species associated with the two 1993 human cases of rabies, and only two of these bats were positive. Rabies was most prevalent in female bats, in bats submitted because of human [corrected] contact, and in animals tested during September and October. These results highlight the unusual circumstances surrounding the recent human rabies cases in the United States. A species of bat rarely encountered by humans, and contributing little to the total rabies cases in bats, has been implicated in the majority of the indigenously acquired human rabies cases in the United States. The factors contributing to the transmission of this rare rabies variant remain unclear. PMID- 7995362 TI - Low prevalence of antibody to human parvovirus B19 in Singapore. AB - A seroepidemiological survey was conducted in Singapore to assess the prevalence of antibody to human parvovirus B19. Sera were collected from 600 healthy individuals between 6 months and over 50 years of age and tested for IgG antibody against B19 virus by antigen capture indirect immunosorbent assay. The overall seropositivity rate was 16.2%. All the children under 5 years of age were seronegative. Antibody prevalence increased gradually from 3.5% in school children (5-14 years of age) to 7.7% in age group 15-19 years and then to 10.3% in young adults (20-24 years of age). In the age group 25-34 years the prevalence was 28% and in the age group over 35 years 65% had parvovirus B19 antibody. The results of the survey indicate that there has been very low incidence of B19 virus infection in Singapore during the last two decades. PMID- 7995364 TI - Serodiagnosis of Crimean-Congo haemorrhagic fever. AB - Several methods for demonstrating antibody to Crimean-Congo haemorrhagic fever virus were compared on serum samples taken from 101 patients during the acute stage of illness and at intervals for up to 59 months thereafter, with emphasis on early detection of the immune response. The deaths of 23 patients on days 5-14 of illness were ascribed to the effects of the disease; two patients died later from other causes. Very few of the patients who died from the acute illness mounted an antibody response detectable by the methods tested. Four patients who died and 18 who recovered were treated with immune plasma collected from recovered patients. Treated patients acquired IgG antibody from the plasma, but it was possible to discern the onset of an endogenous IgM response in those individuals who survived the disease by all of the methods tested. Indirect immunofluorescence (IF) tests detected IgM and/or IgG antibodies at the earliest on day 4 of illness in about 10% of patients who survived the disease, and by day 9 all survivors had antibodies demonstrable by IF. A biotin-streptavidin IF technique offered no advantage over the standard IF test for the early detection of IgG antibody, but demonstrated higher antibody titres and detected IgM antibody earlier in about a quarter of the patients tested. An IgM-capture enzyme linked immunoassay (ELISA) and an IgG sandwich ELISA demonstrated higher antibody titres than did IF tests, and detected antibody responses at an earlier stage of infection than did IF tests in about one-fifth of patients, but the reverse was true in a similar proportion of instances. A competition ELISA, which detected total antibody activity, produced lower titres than did the IgM and IgG ELISAs, but yielded results which were in close agreement with the findings in IF tests. It was concluded that the IF tests were most convenient for use in making a rapid serodiagnosis of the disease. PMID- 7995363 TI - Exposure to enteroviruses and hepatitis A virus among divers in environmental waters in France, first biological and serological survey of a controlled cohort. AB - An epidemiological study of hepatitis A and enteroviruses was conducted in a military diving training school, by evaluating the viral contamination of water using an ultrafiltration concentration technique, and assessing seroconversion and the presence of virus in stool specimens obtained from 109 divers and 48 controls. Three of 29 water specimens were positive for enterovirus by cell culture and 9 by molecular hybridization. There was little or no risk of virus infection during the training course (49 h exposure) because there was no significant difference between divers and controls for both viral isolation and seroconversion. However, a higher percentage of coxsackievirus B4 and B5 seropositive divers suggests that these were more exposed during previous water training. No hepatitis A virus (HAV) detection and no seroconversion to HAV was observed. The rate of HAV seropositive subjects was 17% in this 24.5-year-old population. PMID- 7995366 TI - Human bone marrow microvascular endothelial cells: elusive cells with unique structural and functional properties. PMID- 7995365 TI - Epidemiological evaluation of a monoclonal ELISA detecting antibodies against bovine leukaemia virus in serum pools. AB - Sensitivity, specificity and predictive values of an enzyme-linked immunosorbent assay (ELISA) for detecting antibodies against bovine leukaemia virus (BLV) were evaluated using a representative sample of 145 serum pools, comprising from 3 to 48 individual sera. The sample was constituted according to the frequency distribution of the negative and positive pools analysed during a screening involving the whole cattle population of Belgium. Sensitivity and specificity were estimated to 88.9% and 100% and the predicted negative and positive values were 99.9% and 100%, respectively. These results indicate the use of serum pools is suitable for the detection of BLV infected herds in eradication campaigns. PMID- 7995367 TI - Purified murine long-term in vivo hematopoietic repopulating cells are not prothymocytes. AB - Analysis of kinetics of thymic repopulation by Rh123low, Lin-, Ly6A/E+, c-kit+ (Rh123low) cells, highly enriched for long-term in vivo hematopoietic repopulating cells, reveals that this population is deficient in thymic repopulation at week 3 after intravenous transplantation when compared to normal bone marrow cells. This suggests that the marrow prothymocytes have been depleted from this population, and analysis of thymic repopulation at week 3 can therefore be used to differentiate prothymocytes and their precursors. Using this short term assay, the Rh123high, Lin-, Ly6A/E+, c-kit+ (Rh123high) population has been found to be relatively more efficient at early thymic repopulation, suggesting that this population contains the prothymocytes. In addition, the differentiation potential and reconstitution behavior of the Rh123high population observed after intravenous and intrathymic transfer strongly indicates that this population is at the transitional stage between the marrow primitive pluripotential and thymic more mature lymphoid restricted stem cells. We propose that the thymic repopulating ability of the Rh123low population is through generation of the more mature Rh123high progeny, presumably in the marrow. PMID- 7995368 TI - Multilineal hematopoiesis in a three-dimensional murine long-term bone marrow culture. AB - The highly packed cell density and the three-dimensional structure in the hematopoietic compartment of bone marrow facilitate cell-to-cell and cell-to matrix interactions known to be important for hematopoietic activities. To provide a similar environment in vitro, we developed a long-term bone marrow culture (LTBMC) system, continuously perfused with Dexter's medium, employing packed, highly porous bovine collagen microspheres as the matrix support for marrow cell growth. Using murine bone marrow as a model, we found that the culture system differed from the conventional flask culture in the following ways: 1) as revealed by the electron microscopy, the bone marrow cells in the culture system grew in a three-dimensional configuration, similar to that in vivo, 2) the cell output from the culture system at 37 degrees C was virtually the same as that at 33 degrees C, and 3) in the absence of exogenous growth factors, except those in the serum, the culture system produced lymphoid cells and all stages of committed cells (i.e., erythrocytes, granulocytes, macrophages, and megakaryocytes), thus indicating multilineal differentiation of the hematopoietic stem cells. Furthermore, cell clusters resembling erythroblastic islands were observed in the absence of exogenous erythropoietin (Epo). The culture system appears to provide a different microenvironment than that of the flask culture and may be used as an alternative model for hematopoiesis. PMID- 7995369 TI - Hematopoietic colony assays as predictors of platelet recovery after hematopoietic stem cell transplantation. PMID- 7995370 TI - Isolation and culture of human bone marrow endothelial cells. AB - Bone marrow endothelial cells are likely to play an important role in the homing of hematopoietic progenitor cells. In view of analyzing the interactions between endothelial cells and hematopoietic progenitor cells, we studied several methods of isolating endothelial cells from human bone marrow, including fluorescence activated cell sorting (FACS) and separation by immunomagnetic beads. FACS sorting gave the best results as contamination with other cells did not occur. After density-gradient centrifugation of bone marrow aspirates, the mononuclear cell (MNC) fraction was depleted for T cells, B cells, and myeloid cells by immunomagnetic separation. Further enrichment of endothelial cells was achieved by FACS sorting using BNH9 or S-Endo1 monoclonal antibodies (MAbs). These MAbs, in contrast to several other endothelial-cell reactive MAbs, were found to react highly specifically with sinus endothelial cells as tested by immunohistochemistry on bone marrow tissue sections and cell culture preparations and by double-colored FACS analysis on bone marrow MNCs (BMMNC). Sorted cells, which formed 0.05% of the MNC fraction, showed strong intracytoplasmic von Willebrand factor positivity. Ultrastructural analysis revealed cells with endothelial characteristics. Cells were cultured in fibronectin-coated, 24-well culture plates in endothelial-cell culture medium or long-term bone marrow culture medium. After 1 to 3 weeks of culture, a monolayer of spindle-shaped cells developed expressing endothelial cell antigens. Cells could be kept in culture for 4 to 6 weeks. In conclusion, the method described provides highly purified preparations of human bone marrow endothelium that may permit in vitro adhesion experiments with normal and leukemic hematopoietic progenitor cells. PMID- 7995371 TI - Megakaryocyte-specific positive regulatory sequence 5' to the human PF4 gene. AB - Platelet factor 4 (PF4) is only expressed in platelets and is an appropriate marker for studying megakaryocytic differentiation. We previously characterized cDNA and genomic clones for human PF4 (hPF4) and now present transient expression studies defining the promoter of the gene. 12-O-tetradecanoyl-phorbol-13- acetate (TPA) induces megakaryocytic differentiation of human erythroleukemia (HEL) cells, providing an excellent model system for the study of megakaryocyte specific promoter activity. Luciferase reporter-gene constructs containing sequences from -2074 to +49 were used to map regions that may regulate PF4 gene expression. The sequence in the region -239 to -107 increased basal promoter activity by four- to five-fold in TPA-induced HEL cells. The sequence between 239 and -107 contains 53 consecutive thymidine residues. Functional studies using constructs in this region show that poly(T) and the region -187 to -107 are necessary for the total increase in activity in TPA-induced HEL cells. Mobility shift assays show that the poly(T) tract binds TPA-inducible proteins. The results suggest a complex promoter for the PF4 gene involving a basal nonspecific promoter element between -107 and +49, a positive promoter element between -239 and -107 binding specific nuclear proteins from megakaryocyte-lineage cells, and a silencer-like region between -2074 and -1653. PMID- 7995372 TI - Mehdi Tavassoli, MD 1933-1993. PMID- 7995373 TI - Microcytic anemia in mk/mk mice is not corrected by retroviral-mediated gene transfer of wild-type p45 NF-E2. AB - Mice homozygous for the mk mutation have a severe hypochromic, microcytic anemia that is characterized by a decreased mean-corpuscular hemoglobin concentration and balanced alpha- and beta-globin-chain synthesis. Transplantation studies have shown that the defect in homozygous mk/mk mice is intrinsic to both the hematopoietic system and the gut. The gene for the hematopoietic-specific transcription factor, p45 NF-E2, has been found to cosegregate with the mk phenotype and contain a point mutation in mk/mk mice that results in an amino acid substitution (173V-->A). In order to test the hypothesis that this amino acid substitution is responsible for the mk phenotype, we have used recombinant retroviruses to introduce wild-type p45 NF-E2 into the bone marrow of mk/mk mice. Despite gene transfer and expression of p45 NF-E2 in erythroid cells, we found no evidence for correction of the phenotype in mk/mk mice. These results indicate that the mk mutation cannot be corrected by enforced expression of wild-type p45 NF-E2 and suggest that the 173V-->A mutation of the p45 NF-E2 gene is not the cause of anemia in mk/mk mice. PMID- 7995374 TI - A pathogenetic link between aplastic anemia and paroxysmal nocturnal hemoglobinuria is suggested by a high frequency of aplastic anemia patients with a deficiency of phosphatidylinositol glycan anchored proteins. AB - The clinical interrelationship between paroxysmal nocturnal hemoglobinuria (PNH) and aplastic anemia (AA) promoted a search for a pathogenetic link. Since the molecular defect in PNH is a failure to express phosphatidylinositol glycan anchored proteins (PIG-AP), we investigated whether this defect could also be demonstrated on peripheral blood cells of patients with typical AA. Quantification of the expression of PIG-AP was performed by flow cytometry using the monoclonal antibodies (MAbs) CD16 and CD66b for granulocytes, CD14 and CD48 for monocytes, CD48 and CD52 for lymphocytes, and CD55 and CD59 for erythrocytes. We analyzed cells from 52 patients with acquired AA. A PIG-AP-defective population was identified in 27 of 52 patients (52%) in at least one cell lineage. Granulocytes were involved in 25 of 27, monocytes in 18 of 25, lymphocytes in seven of 27, and erythrocytes in seven of 27 AA patients who were affected by a PIG-AP deficiency. The response rate to standard immunosuppressive therapy was significantly higher in the group of patients without a PIG-AP deficient population than in patients with a PIG-AP-deficient population in at least one cell lineage (85.7 vs. 30.4%; p < 0.0003). Our results demonstrate that on the basis of PIG-AP expression, the proportion of AA patients who show features of typical AA along with a PNH phenotype is substantially higher than previously recognized. The pattern of PIG-AP expression might identify subgroups of AA patients who differ in the underlying mechanism as well as in the course of their disease. PMID- 7995376 TI - Role of extravascular gas bubbles in spinal cord injury induced by decompression sickness in the rat. AB - We have evaluated the contribution of extravascular gas bubbles to spinal cord injury in decompression sickness. For this purpose, a model of decompression sickness was developed by subjecting rats to simulated dives using compressed air. Various diving profiles were tested and the presence of spinal cord injury was demonstrated by electrophysiologic measurements. To evaluate the space occupying lesions induced by gas bubbles in the white matter, the spinal cord was fixed by perfusion with 10% buffered formalin. Tissue blocks from cervical, thoracic, and lumbar spinal cords were embedded in paraffin. Tissue sections were double stained with luxol fast blue and hematoxylin and eosin. The space occupying lesions were quantified with a digitizer tablet. The fractional area of the lesions was 0.009% in controls and 0.026% in rats subjected to diving. We conclude that the volume of extravascular free gas present in the cord of rats with spinal decompression sickness is small and that artifacts of tissue preparation contribute to the volume estimate. As far as can be judged from the results in this animal model, the contribution of extravascular gas bubbles to spinal cord decompression injury is minor. PMID- 7995375 TI - Biliary glutathione and some amino acids are markedly diminished when biliary pressure is elevated. AB - We studied the effects of a transient elevation in biliary pressure on biliary glutathione and amino acids in rats. Other biliary solutes monitored were total bile salt, Pi, which is a putative marker of paracellular leakage, and glucose, which is reabsorbed from the biliary tract. Experiments were carried out on anesthetized rats intraduodenally infused with taurocholate to maintain bile flow during a 2-hr basal period, a 4-hr pressure period during which the bile duct cannula was elevated until bile flow decreased to 1/3 the basal rate, and a 2-hr period after release of hydrostatic biliary pressure. We found that pressure treatment caused biliary concentrations of glutathione to progressively decrease by 80%, while biliary Pi rapidly rose approximately 3- to 4-fold, bile salt gradually increased approximately 3-fold, and biliary glucose concentration progressively rose 15-fold. HPLC analysis of monobromobimane-derivatized biliary thiols indicated that the decline in biliary glutathione was not accompanied by an increase in its breakdown products, cysteine and cysteinylglycine. Pressure treatment led to four patterns of change in biliary amino acid concentrations: (1) increases of 29 to 76% for the basic amino acids lysine and arginine, which have very low bile/plasma ratios of about 0.1; (2) no change for the more water soluble amino acids with bile/plasma ratios close to 1.0, e.g., histidine and urea; (3) modest decreases of 16 to 48% for a variety of amino acids including serine, glutamate, and glycine; and (4) marked, progressive decreases of > 50% for aromatic and branched chain amino acids. By 2 hr after release of pressure, only the alterations in biliary glucose and some amino acids, particularly the branched chains, persisted. This is the first report of cholestasis-induced alterations in biliary amino acids. PMID- 7995377 TI - Ultrastructural differences between pulmonary arteriolar muscularization induced by hypoxia and monocrotaline. AB - A group of Wistar rats was treated with two subcutaneous injections of monocrotaline, at 4 and 6 weeks of age. They were then killed 1 month after the initial injection. A second group of rats was born and reared in hypobaric hypoxia for 1 month before being killed. Both groups had age-matched controls. The ultrastructure of pulmonary arterioles from all groups was studied, and quantitative measurements were made of the volume densities of organelles within the cytoplasm of arteriolar smooth muscle cells. The pulmonary arterioles of rats treated with monocrotaline contained immature smooth muscle cells with coarse peripheral myofilaments and were bounded by thin indistinct elastic laminae. In contrast, the arteriolar smooth muscle cells of hypoxic rats were mature with fine myofilaments and bounded by electron dense laminae. When compared with both their respective controls and the alternative test group, the muscle cells from rats treated with monocrotaline had significantly lower volume densities of dense bodies, and the hypoxic muscle cells had significantly higher densities of mitochondria. The pulmonary arteriolar muscularization in rats would appear to be a nonuniform process producing smooth muscle cells with differing cytoplasmic features that suggest differing cellular functions. PMID- 7995378 TI - Ultrastructural analysis of skin and aorta from a patient with Menkes disease. AB - Ultrastructural studies of the skin and aorta of a patient with Menkes disease, an X-linked recessive disorder of copper metabolism, are described. Dermal thickness was normal, while dermal collagen fibrils exhibited a heterogeneous size range, with a mean diameter smaller than normal. Long-spacing collagen was often observed near fibroblasts, the plasma membranes of which were decorated by aggregates of interwoven filaments. Dermal elastin fibers were scarce and consisted of thin strands of amorphous elastin associated with numerous microfibrils. In the aorta, the amount of collagen was normal, although the fibrils displayed a broader range of diameters than normal, with a slightly smaller mean. Elastin fibers showed considerable disruption, appearing fragmented and wider than normal, and displaying irregular contours. The inclusion of cationic dyes during tissue fixation gave rise to numerous electron-dense precipitates within the elastin fibers, suggesting the presence there of glycosaminoglycans or proteoglycans, among which unsulfated and sulfated chondroitins were demonstrated by immunoelectron microscopy to be prominent. Heparan sulfate, observed to be a constituent of normal elastin fibers, was much reduced in amount. Elastin was also found associated with glycosaminoglycans in the soluble matrix of the aortic wall. PMID- 7995379 TI - Modifications in myotendinous junction surface morphology in dystrophin-deficient mouse muscle. AB - Single muscle fibers from mdx mouse muscle, which is deficient in dystrophin, and control mouse muscle, containing dystrophin, were compared by scanning electron microscopy. In particular, comparisons were made of the surface morphology at myotendinous junctions and costameres, sites at the muscle cell surface that are enriched in dystrophin and where force is transmitted across the cell membrane. Muscle fibers from 4- and 6-week-old controls display nearly uniform surface morphology characterized by numerous digit-like processes at the myotendinous junction and nonjunctional surface membrane possessing distinct grooves at sites corresponding to underlying costameres. Mdx fibers at this stage showed blunted myotendinous junctions with few digit-like processes, infrequent indistinct costameric markings, and holes in the cell membrane. Cells from peak regenerating mdx muscle (6 weeks) showed surface morphology similar to 4-week mdx fibers, although the proportion of fibers displaying extensive structural defects was reduced at 6 weeks. Completely regenerated mdx fibers (23 weeks) were indistinguishable from fibers of 6-week-old mdx mice. In control mice, only approximately 6% of the fibers examined from 4- or 6-week-old mice showed any of the structural defects characteristic of the majority of mdx fibers. However, fibers from 23-week-old control mice displayed an increased frequency of cells with poorly defined junctional processes and surface striations. These findings indicate that the fibers displaying extensive disruption of surface features, which are most commonly observed in 4-week mdx mice at peak necrosis, are necrotic fibers. Specific defects, such as the reduction in myotendinous junction folding, loss of costameres, and increased occurrence of membrane holes, are observed in the majority of mdx fibers at all ages. Thus, these defects are more directly attributable to dystrophin's absence because their frequency of occurrence is independent of the stage of necrosis and regeneration. PMID- 7995380 TI - Effect of lead on the biological activity of calmodulin in rat brain. AB - In the present investigation, we observed that lead in vitro activates calmodulin at lower concentrations, and the maximum activation was observed at 30 microM concentration. In vivo lead exposure (50 mg/kg body weight, intragastrically) for a period of 8 weeks also stimulated the activity of calmodulin by 45%. The addition of trifluoperazine resulted in partially inhibiting the lead-stimulated calmodulin activity, whereas the calcium-stimulated calmodulin activity was completely inhibited by trifluoperazine. Studies with purified calmodulin from the brain of control and lead-treated animals indicate that approximately 4 mole of calcium was present bound/mole of calmodulin in control animals and this fraction was reduced in lead-treated animals to approximately 3 mole of calcium/mole of calmodulin. Lead distribution revealed that approximately 68% of the total lead present was bound to calmodulin and the remaining 32% present was bound to non-calmodulin binding sites following lead exposure. These results indicate that in vivo lead exposure is able to displace and mimic the action of calcium and this may constitute a molecular mechanism of lead neurotoxicity. PMID- 7995381 TI - Low molecular weight pollutants and asthma: pathogenetic mechanisms and genetic factors. PMID- 7995382 TI - HIV-related tuberculosis due to Mycobacterium bovis. PMID- 7995383 TI - Airway inflammation after removal from the causal agent in occupational asthma due to high and low molecular weight agents. AB - In order to determine 1) the features of airway inflammation after removal from exposure to high (HMW) and low (LMW) molecular weight agents 2) if there are any differences in the pattern of inflammation induced by these two types of agents, we studied 18 subjects with a recently confirmed diagnosis of occupational asthma (OA) due to HMW (n = 11) and LMW (n = 7) agents. The duration of asthma symptoms varied from 2 to 108 months (mean 33 months), and withdrawal from exposure to the sensitizing agent from 3 to 24 weeks (mean 10 weeks). All subjects underwent measurements of expiratory flow rates, methacholine inhalation tests, and a flexible bronchoscopy with bronchoalveolar lavage (BAL) and bronchial biopsies. Endoscopic findings were compared with a group of 10 normal subjects. At the time of the bronchoscopy, asthma symptoms were minimal in most subjects. Although 15/18 subjects had normal forced expiratory volume in one second (FEV1 > 80% pred), all subjects had increased airway responsiveness to methacholine (provocation concentration producing a 20% fall in FEV1 = 0.2-10.0 mg.ml-1). BAL analysis showed similar median percentages of the total number of cells and differentials in control subjects and those exposed to HMW and LMW agents. Bronchial biopsies showed that mean inflammatory cell count, both epithelial and sub-epithelial, was similarly raised in OA subjects exposed to either HMW or LMW agents, compared to controls, except for epithelial lymphocyte count. In contrast to the controls, bronchial biopsy of both groups with OA also showed other changes such as extensive epithelial desquamation, ciliary abnormalities of the epithelial cells, smooth muscle hyperplasia and subepithelial fibrosis.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7995384 TI - Granulocyte-macrophage colony-stimulating factor, eosinophils and eosinophil cationic protein in subjects with and without mild, stable, atopic asthma. AB - Increasing evidence implicates the eosinophil as an important effector cell in asthma, but little is known regarding its regulation in vivo. Granulocyte macrophage colony-stimulating factor (GM-CSF) has been shown to regulate eosinophil function in vitro. We investigated the in vivo role of eosinophils and GM-CSF in mild asthma. We compared the number and function of eosinophils and the presence of GM-CSF in blood, bronchoalveolar lavage (BAL) and biopsy tissue obtained from eight mild, stable, atopic asthmatics and 10 nonasthmatics, five of whom were atopic and five nonatopic. Eosinophils were significantly increased in the blood, BAL and biopsy tissue from asthmatics. Activated eosinophils, assessed by immunostaining for the secreted form of eosinophil cationic protein (EG2), were also increased in asthmatic BAL cells and biopsy tissue. Significant increases in GM-CSF in BAL cells and biopsy tissue from asthmatics were also evident. Significant positive correlations existed between GM-CSF in BAL and EG2, and GM-CSF in biopsy tissue and BAL and biopsy eosinophils. Airway responsiveness was also significantly positively correlated with eosinophil number and activation, and with GM-CSF. These results demonstrate that there are increased numbers of activated eosinophils and GM-CSF is increased in patients with mild asthma. Furthermore, GM-CSF is correlated with eosinophil number and function in vivo and these indices are significantly correlated with airway function. These findings emphasize the importance of eosinophils, potentially regulated in vivo by GM-CSF, in contributing to the disordered airway function evident even in mild asthma. PMID- 7995385 TI - Enhancement of reactive oxygen species formation in stable and unstable asthmatic patients. AB - There is increasing evidence to suggest that human blood polymorphonuclear neutrophils (PMNs) and monocytes play an important role in the inflammatory processes of asthma. In asthmatic patients, PMNs and monocytes were shown to be activated more than in healthy subjects. We investigated the capacity of these two cell populations to generate reactive oxygen species (ROS) in stable and unstable asthmatic patients. The two populations of asthmatic patients were identified by asthma activity, as expressed by clinical events occurring within 2 weeks prior to the study. Oxygen species formation was analysed for isolated purified PMNs and monocytes (Mos) by chemiluminescence (CL) using lucigenin and luminol as luminescent probes. CL was determined on nonstimulated and on phorbol myristate acetate (PMA)-stimulated cells. The stimulatability coefficient (PMA stimulated/nonstimulated cell ratio) of each cell population was then calculated. Resting PMNs and Mos generated significantly greater amounts of ROS in stable asthmatic patients, and much more in unstable asthmatic patients, as compared to healthy subjects, both in lucigenin and luminol enhanced CL. Non O2.- ROS production from PMA-stimulated PMNs and Mos was identical in unstable asthmatic patients and in healthy subjects, whereas a significant decrease was observed in stable asthmatic patients, as assessed by luminol enhanced CL. PMA-stimulated cells showed no difference in O2.- generation, as assessed by lucigenin enhanced CL. However, the stimulatability coefficient of all asthmatic patients was always significantly lower than that of healthy subjects. These results suggest that there are differences in priming and stimulation of Ros production from PMNs and Mos between stable and unstable asthmatic patients.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7995386 TI - High dose inhaled atrial natriuretic peptide is a bronchodilator in asthmatic subjects. AB - Atrial natriuretic peptide (ANP) has been shown to be an effective bronchodilator when given intravenously, but its efficacy by inhalation has not been assessed. In the first part of the current study, six asthmatic subjects, mean (SEM) forced expiratory volume in one second (FEV1) 2.09 (0.30) l, received 0.1 and 1 mg atrial natriuretic peptide by inhalation, and in the second study five subjects, FEV1 1.92 (0.40) l, received 5 mg ANP by inhalation. ANP was given in a placebo controlled, double blind, randomized manner, with measurement of FEV1 over the following 60 min. Nebulized salbutamol was given at 60 min as a measure of the maximal bronchodilator response attainable by conventional therapy. No significant bronchodilator effect was seen following the 0.1 or 1 mg inhalation, although the latter produced a minimal transient elevation in peripheral atrial natriuretic peptide plasma levels. A bronchodilator effect was seen with the 5 mg dose, which produced delta FEV1 0.42 (0.09) l compared to 0.93 (0.13) l subsequently produced by salbutamol. This effect peaked at 5 min and was no different from placebo from 10 min onwards. We conclude that atrial natriuretic peptide may produce significant bronchodilation when given by inhalation in high doses, and speculate that substances which generate cyclic guanosine monophosphate (cGMP) in airway smooth muscle warrant further investigation as potential bronchodilatory agents. PMID- 7995387 TI - Terbutaline via pressurised metered dose inhaled (P-MDI) and Turbuhaler in highly reactive asthmatic patients. AB - There is some concern over the environmental consequences of chlorofluorocarbons (CFCs) used in pressurized metered-dose inhalers (p-MDIs). Turbuhaler was designed to deliver a drug as a dry powder without administering additives directly to the airways. The aim of this study was to evaluate the comparative irritant and bronchodilating effects of the same dose of terbutaline delivered by a p-MDI and via Turbuhaler. Ten symptomatic, asthmatic patients, with highly reactive airways (provocative concentration of methacholine producing a 20% fall in forced expiratory volume in one second (PC20) < 0.2 mg.ml-1), inhaled, on separate days, 0.25 mg terbutaline via p-MDI or Turbuhaler. Changes in airway calibre were followed as specific airways conductance (sGaw). On a third day, patients inhaled from a placebo p-MDI containing all constituents except terbutaline. The study was conducted in a single-blind fashion and in random order. There were no significant differences in baseline sGaw on any of the study days. Inhalation of terbutaline from the p-MDI produced a transient percentage fall in sGaw at 1 min, reaching a mean maximum +/- SD of 17 +/- 8% at 10 s and then returning to baseline value after 20 s, followed by a progressive increase in sGaw to a maximum of 39 +/- 45% above baseline at 45 min. In contrast, inhalation of terbutaline via Turbuhaler caused no significant bronchoconstriction (fall in sGaw, 3 +/- 16%) at 10 s and achieved a greater increase in sGaw, reaching 63 +/- 51% at 45 min, although just failing to reach statistical significance compared to terbutaline p-MDI inhalation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7995388 TI - Patterns of increasing beta-agonist use and the risk of fatal or near-fatal asthma. AB - The association between the use of inhaled beta-agonists by metered-dose inhaler and the risk of fatal or near-fatal asthma has been demonstrated. It shows that asthmatics who use one canister of beta-agonist per month more than the number used by other similar asthmatics have twice the risk of fatal or near-fatal asthma. The present investigation assesses the magnitude of this excess risk when an asthmatic increases his/her own monthly use of inhaled beta-agonists over time. From a previous nested case-control study of 129 deaths and near-deaths from asthma (cases) and 655 controls from a cohort of 12,301 asthmatics, the subset using at least 12 inhalers during the 12 month study period was identified (97 cases and 258 controls). A profile score, ranging 0-11, was formed to quantify the patterns of beta-agonist use over time for each subject, covering the entire spectrum extending from decreasing to increasing use. The relative risk was 15.2 (95% confidence interval (CI) 2.4-96.2) per unit increase of the profile score in subjects with a pattern of increasing beta-agonist use (profile score of 6.5 or more), but this relative risk was only 1.5 (95% CI 0.8-2.6) per unit when the profile score was less than 6.5 (non-increasing use). This relative risk was independent of the risk associated with the total quantity of beta agonist use in the 12 month period, which remained around 1.6 (95% CI 1.3-2.0) per inhaler per month.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7995389 TI - Beta 3-adrenoceptor agonists, BRL 37344 and SR 58611A, do not induce relaxation of human, sheep and guinea-pig airway smooth muscle in vitro. AB - The existence of atypical- or beta 3-adrenoceptors has now been generally accepted. These receptors have been shown to be abundant in adipose tissue and in a number of gastrointestinal smooth muscle preparations. A recent study reported that beta 3-adrenoceptor stimulation mediated relaxation of isolated canine bronchial smooth muscle. The aim of the present study was to extend this observation to other species. We investigated the in vitro responses of guinea pig, human and sheep bronchial smooth muscle to isoprenaline, salbutamol (a selective beta 2-adrenoceptor agonist), and BRL 37344 and SR 58611A (two presumably selective beta 3-adrenoceptor agonists). The preparations were precontracted to 60-70% of maximal tension with histamine 10(-6) M for guinea-pig and human bronchi, or acetylcholine 10(-6) M for sheep bronchi. In each species, SR 58611A produced a slight fall in tension of about 10% of the effects of theophylline (3 mM), but this decrease in tension was not significantly different from the spontaneous and weak relaxation observed with saline addition during the same duration of the experiment. These relaxations were not modified by either the nonselective beta-adrenoceptor antagonist propranolol or the selective beta 2 adrenoceptor antagonist ICI 118,551. In contrast, BRL 37344 induced a significant concentration-dependent fall in tension induced by both spasmogens. Its relaxant effects were inhibited both by propranolol and ICI 118,551 in human and guinea pig airways, whereas on the isolated sheep bronchus BRL 37344-induced relaxations were only slightly, albeit significantly, reduced with either of the beta adrenoceptor antagonists tested.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7995390 TI - Exogenous surfactant enhances mucociliary clearance in the anaesthetized dog. AB - Therapy with exogenous surfactants is currently used for the treatment of respiratory distress syndrome of the newborn (RDS) and is under investigation for treatments related to adult RDS. However, the possible use of exogenous surfactant as a means of enhancing mucus clearance in other respiratory diseases has not been addressed. We therefore studied the effects of an artificial surfactant (Curosurf) on in vivo tracheal mucus velocity in intubated pentobarbital-anaesthetized dogs. Five dogs were randomly administered, on separate occasions, either vehicle (saline) or 10 mg Curosurf by means of local instillation via a catheter into the right lung. Tracheal mucus was collected by inserting a soft-bristled cytology brush to the level of the carina, and analysed for viscoelasticity by microrheometry. Mucociliary clearability in vivo, tracheal mucus velocity (TMV) in mm.min-1, was determined by bronchoscopic observation of charcoal marker particle transit times. The initial placement of charcoal was at the same level of the lower trachea that mucus was collected from. The effect of ciliary beat frequency was assessed on the frog palate assay by a videoscopic technique. In the dog, TMV was significantly increased after administration of surfactant. The values of TMV in the vehicle- and surfactant-treated dogs were 6.3 +/- 4.0 vs 25.6 +/- 6.5 mm.min-1 (SD), respectively. There were no discernible differences between prevehicle and postvehicle TMV values, and no significant differences in any mucus viscoelastic parameter, as determined by magnetic rheometry.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7995391 TI - Stimulation of Cl- secretion by the mucoactive drug S-carboxymethylcysteine lysine salt in the isolated rabbit trachea. AB - Ion transport by the airway epithelium contributes to the regulation of the quantity and composition of respiratory tract fluid, thereby affecting mucociliary clearance. We have investigated the effect of the mucoactive drug S carboxymethylcysteine-lysine salt (S-CMC-Lys) on the transepithelial bioelectric properties of isolated rabbit trachea. Transepithelial potential difference (Vms), short-circuit current (Isc) and resistance (R) were measured in the isolated rabbit trachea mounted between flux half-chambers, in the presence and in the absence of S-CMC-Lys (100 microM), added to the mucosal or submucosal chamber. In some experiments, tissues were also exposed to ion channel inhibitors, in order to evaluate the contribution of Na+ and Cl- active transport to Isc. The excised rabbit trachea expressed transepithelial bioelectric properties based on an active ion transport supported by the Na(+)-K(+)-adenosine triphosphatase (ATPase) activity, since ouabain (500 microM) completely abolished the transepithelial potential difference. In control preparations, Vms and Isc declined significantly during 300 min recording, whereas R remained constant. The Isc decline was essentially attributable to a decrease in Cl- transport. Bumetanide (100 microM) almost completely abolished the Isc fraction related to Cl- transport. Treatment of the tissues with S-CMC-Lys reduced the progressive fall in Isc, with the most clear-cut and significant effect observed for the mucosal treatment. In parallel, S-CMC-Lys significantly lowered R, without affecting Vms. Either mucosal or submucosal exposure to S-CMC-Lys significantly increased Cl- secretion to normal values, whilst Na+ absorption was not modified.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7995392 TI - Protective effect of ambroxol against heat- and hydrogen peroxide-induced damage to lung lipids in mice. AB - We wanted to determine whether ambroxol, a drug which stimulates the release of surfactant by type II pneumocytes, can protect lung lipids from peroxidative damage in mice. Animals were injected intraperitoneally with ambroxol, 0.169 mmol.kg-1, or 1 ml buffer once a day for three consecutive days. Lipid peroxidation was then induced in lung homogenates either by means of heat, 50 degrees C, or H2O2, 10 mmol.l-1. The lung homogenates from ambroxol-treated animals revealed decreased lipid peroxidation in response to both stimuli. The heat- and H2O2-induced generation of conjugated dienes (a first lipid peroxidation product) in ambroxol-treated lung homogenates was 3.7 and 3.1 fold lower than in the lungs from buffer-injected mice. Ambroxol, as an inhibitor of heat- and H2O2-induced lipid peroxidation, was equipotent to and stronger than the two antioxidants, N-acetylcysteine and methionine, respectively. Ambroxol was not able to protect heart and liver lipids. These results suggest that ambroxol can sufficiently enhance the antioxidant defence in lung tissue and can act as a lung lipid antioxidant. PMID- 7995394 TI - Home versus hospital intravenous antibiotic therapy in the treatment of young adults with cystic fibrosis. AB - We wanted to investigate whether home intravenous antibiotic treatment of pulmonary exacerbations of cystic fibrosis is as effective as treatment in hospital. The case records of all patients attending the Leeds adult cystic fibrosis clinic were reviewed to identify those who had received home intravenous antibiotic treatment. All home treatments undertaken were included. For each home treatment, the temporally closest hospital treatment for that patient was then selected for comparison and the changes with treatment in peak expiratory flow rate (PEFR), forced vital capacity (FVC), forced expiratory volume in one second (FEV1), C-reactive protein (CRP), plasma viscosity, total white cell count, absolute neutrophil count, total immunoglobulin G (IgG) concentration, chest X ray score (Northern), clinical score, Shwachman-Kulczyki score and weight were analysed for differences between home treatment and hospital treatment. Fifty one paired home/hospital treatments in 25 patients were compared. The improvement in total white cell count was found to be significantly greater in the hospital group, but the difference was very small. The improvements in absolute neutrophil count, and all the other measured variables, were the same in the two groups. Treatment of exacerbations of cystic fibrosis at home or in hospital is, thus, equally effective given proper patient selection and adequate monitoring of the response to treatment. PMID- 7995393 TI - A hospital outbreak of penicillin-resistant pneumococci in The Netherlands. AB - Respiratory infections with penicillin resistant pneumococci constitute an increasing health care problem. This paper describes the nosocomial spread of penicillin resistant pneumococci (PRP) on a pulmonary ward. During an eight-month period, minimal inhibitory concentrations (MICs) for penicillin and several other antibiotics were performed on all Streptococcus pneumoniae isolates that were shown to be penicillin resistant by a screening assay. The personal data and case history of all patients with penicillin resistant pneumococci were evaluated. Penicillin Resistant Pneumococci were cultured from 18 patients, 16 men (mean age 74 +/- 8 yrs) and 2 women (aged 54 and 60 yrs). Chronic obstructive pulmonary disease was diagnosed in 16 patients, 10 of which had an additional underlying disease (2 diabetes mellitus, 2 heart failure, 2 malignancy). Prior to culture of Penicillin Resistant Pneumococci, 11 out of 18 patients were treated with antibiotics, a beta-lactam in most instances. Ten out of 18 patients died during or shortly after hospitalization. The death of one patient seems to be directly related to infection with Penicillin Resistant Pneumococci. The five Penicillin Resistant Pneumococci isolates available for serotyping were all type 9. The minimal inhibitory concentrations for penicillin varied from 0.5 to 2.0 mg.l-1. High minimal inhibitory concentrations were also noted for cefixime (all over 4.0 mg.l-1) and ceftriaxone (0.5-1.0 mg.l-1). It is concluded that penicillin resistant pneumococci can spread rapidly among old and debilitated patients. Thus, patients with this infection should be barrier nursed. PMID- 7995395 TI - Survival and prediction of successful ventilator weaning in COPD patients requiring mechanical ventilation for more than 21 days. AB - We studied survival and failure or success of weaning from mechanical ventilation (MV) in 42 consecutive chronic obstructive pulmonary disease (COPD) patients requiring prolonged MV (more than 21 days) after an episode of acute respiratory failure requiring admission to our Intermediate Intensive Care Unit (IICU). Parameters including arterial blood gases, pulmonary function tests, respiratory muscle force, neuromuscular drive, and nutritional status were recorded during a phase of clinical stability, in order to identify the features related to survival and weaning. All the patients were submitted to a comprehensive rehabilitation programme. Successful weaning from MV was defined as complete respiratory autonomy for at least 48 h. Twenty three patients were successfully weaned from MV after an average period of 44 days (Group A), requiring no further MV during their stay in hospital, whilst the remaining 19 patients were not able to be disconnected from the ventilator (Group B). The discriminant analysis showed that weaning from MV was significantly associated with arterial carbon dioxide tension (PaCO2), neuromuscular drive (P0.1), maximal inspiratory pressure (MIP), arterial oxygen tension (PaO2), the ratio of respiratory frequency to tidal volume (f/VT) and the serum protein level. Other pulmonary function tests (forced expiratory volume in one second (FEV1), FEV1/forced vital capacity (FVC), anthropometric data, nutritional status, number of pulmonary exacerbations during MV and evidence of cor pulmonale, were similar in the two groups. The discriminant equation considering PaCO2 and MIP could separate the two groups with an accuracy of 84%. The overall survival at 2 yrs was 40%; in Group B it was significantly lower than in Group A (22 vs 68%). Most of the deaths occurred within the first 120 days after intubation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7995396 TI - The ageing of lung function: cross-sectional and longitudinal studies of an Inuit community. AB - Three surveys (1969/1970, 1979/1980 and 1989/1990) have examined the impact of acculturation to a sedentary lifestyle on the pulmonary function of a circumpolar native Inuit community. The sample comprised more than 50% of those aged 20-60 yrs, most recently 119 males and 92 females. Forced vital capacity (FVC), forced expiratory volume in one second (FEV1) and maximal mid-expiratory flow (MMEF) were measured by standard spirometric techniques, and information was obtained on smoking habits and health. Multiple regression equations showed that lung function was affected by height and age, but usually not by age squared. Cross sectional age coefficients for FVC and FEV1 increased over the period 1969/1970 to 1989/1990. Parallel longitudinal trends were seen in FEV1 (males only). Multiple analysis of variance (MANOVA) showed age-decade*cohort effects for FVC and FEV1 (males but not females). Almost all of the population now smoke (mean +/ SD males 13 +/- 8 cigarettes.day-1; females 11 +/- 7 cigarettes.day-1). However, smoking bears little relationship to lung function perhaps due to limited variance in consumption. About a third of the community have physician-diagnosed and/or radiographically visible chest disease, but with little effect upon pulmonary function. We conclude that an apparent secular trend to a faster ageing of lung function in men is not explained by disease or domestic air pollution. Possible factors include increased lung volumes in young adults, greater pack years of cigarette exposure, nonspecific respiratory disease, increased inspiration of cold air or altered chest mechanics due to operation of high-speed snowmobiles, and loss of physical fitness. PMID- 7995397 TI - Lung function by tidal breathing in awake healthy newborn infants. AB - The increasing availability of appliances for measuring lung function in infants may allow clinical and epidemiological applications. The aim of the present study was to establish reference values for tidal breathing lung function in awake newborn infants and to investigate potential sources of variability. Tidal flow volume loops were measured in 803 awake, healthy infants (427 males and 376 females) and passive respiratory mechanics (single-breath occlusion technique) in 664. Mean postnatal age was 2.7 +/- 0.9 (sd) days, gestational age 39.8 +/- 1.4 weeks and birthweight 3.59 +/- 0.49 kg. Tidal expiratory volume (Vt), peak tidal expiratory flow (PEF), and mid-expiratory flow increased significantly with increasing birthweight. Flow ratios: ratio of time to PEF to total expiratory time (Tpef/Te), ratio of volume to PEF to total expiratory volume (Vpef/Ve); and ratio of tidal flow at 25% remaining expiration to PEF (TEF25/PEF), were highest in 1 day old infants (medians 0.39, 0.46 and 0.81 respectively), decreasing to a minimum in 4-5 day old infants, but were not influenced by birthweight. Tidal flows and flow ratios were higher in males versus females, even after weight adjustment. Respiratory rates correlated significantly with tidal flows (r = 0.66), inversely with Vt (r = 0.40), but not with flow ratios. Mean compliance of the respiratory system was 1.18 ml.cmH2O-1.kg birthweight (95% confidence interval (95% CI) 1.15-1.21) and mean resistance 0.051 cmH2O.ml-1.s (95% CI 0.049 0.054). These results demonstrate that lung function in awake healthy infants varies according to weight, gender and postnatal age.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7995398 TI - The lung in closeview: a corrosion casting study on the vascular system of human foetal trachea. AB - The aim of this study was to examine the tracheal vasculature in 5 month human foetuses, and to determine whether it differs from that previously described by other authors for adult human trachea. The vascular bed was visualized using the technique of corrosion casting and examined by scanning electron microscopy. The arrangement of larger vessels: longitudinal tracheo-oesophageal arteries and veins, as well as their segmental branches running circumferentially in the intercartilaginous spaces, was similar to that observed in the trachea of adults. However, no blood sinuses reported to occur in the submucous venular plexus of the human trachea could be found in the foetuses. It is postulated that the possible functions of such sinuses acting as the capacitance system are related to the functional respiratory tract; hence, this vascular specialization is not yet developed in the foetus. PMID- 7995400 TI - Airway goblet cells: responsive and adaptable front-line defenders. AB - Goblet cells are situated in the epithelium of the conducting airways, often with their apical surfaces protruding into the lumen, a location which fits them for a rapid response to inhaled airway insults. Together with the submucosal glands, goblet cells secrete high molecular weight mucus glycoproteins (mucins), which confer upon the airway surface fluid the requisite biochemical and biophysical properties which determine the efficiency of entrapment and transportation of inhaled irritants, particles and micro-organisms. The diversity of glycosylation of airway mucins may be important in facilitating adherence of micro-organisms to mucus prior to mucociliary clearance. Other secretory products, including lipids and "small" glycoproteins, may also be produced by goblet cells. It is possible that goblet cells have the potential to produce markedly more mucus than do the glands. Mucins are tightly packed in the intracellular granules of the goblet cell. The morphology of these granules varies with fixation technique, and release of mucins may be via a combination of merocrine and apocrine secretion. Discharge of mucus is accomplished remarkably rapidly (tens of milliseconds) and vast quantities of mucus are released (size expansions from the granule of many hundredfold). Depending upon species and preparation, goblet cells discharge mucus in response to a wide variety of stimuli, including proteinases, irritant gases, inflammatory mediators, reactive oxygen species, nerve activation and changes in the biophysical environment. Under normal conditions, goblet cell proliferation and differentiation, particularly to ciliated cells, contributes to maintenance of the airway epithelial cell population. In addition to participating in acute airway defence, goblet cells increase in number in response to chronic airway insult, with a resultant increase in output of mucus. The increase in number of cells is via hyperplastic and metaplastic mechanisms. Early triggers for the development of a hypersecretory epithelium include excessive discharge of mucus and increased expression of airway mucin messenger ribonucleic acid (mRNA). Cessation of chronic airway stress rapidly reverses the increased number of goblet cells. Irritant-induced increases in number of goblet cells can be inhibited by a variety of drugs with anti-inflammatory and mucoregulatory properties, and the reversal to normal numbers after cessation of the irritation is speeded by these drugs. The ability of goblet cells to be progenitors of ciliated cells, to rapidly produce vast quantities of mucus in response to acute airway insult, and to change in number according to variations in chronic insult indicates that these cells are vitally important responsive and adaptable front-line defenders of the airways. PMID- 7995401 TI - Multiple actuations of salbutamol MDI into a spacer device reduce the amount of drug recovered in the respirable range. AB - We wanted to determine the amount of salbutamol available in respirable particles from the Volumatic spacer device after one, two or five actuations of a metered dose inhaler into the spacer prior to analysis. A glass multistage liquid impinger was used to determine particle size. Aerosol was sampled after one, two or five actuations from a metered-dose inhaler into a Volumatic spacer. Each experiment was repeated four times. The amount of salbutamol recovered per actuation in particles less than 5 microns (mean and 95% confidence intervals) was: 54.3 micrograms (48.3-60.1) after one actuation; 42.4 micrograms (38.2-46.5) after two actuations, and 20.7 micrograms (17.5-23.9) after five actuations. We conclude that multiple actuations of salbutamol into the Volumatic spacer do not linearly increase the amount of drug available for inhalation. To maximize drug delivery, single actuations should be used prior to inhalation. In comparative studies of drugs and dosages, it must be remembered that the amount of drug delivered is not the same as that administered. PMID- 7995399 TI - Pulmonary macrophages. AB - Interest in pulmonary macrophage research has greatly increased as is now possible not only to work with the easily accessible alveolar macrophages but also with macrophages prepared from lung tissue, such as the interstitial macrophages, dendritic cells and intravascular macrophages. A fascinating aspect is that, in one organ, the modulation of macrophage functions according to their anatomical localization can be studied. This article tries to review some of the modern aspects of research on pulmonary macrophages. These include localization and origin of the various subpopulations, membrane receptors and surface markers, arachidonic acid metabolism, antimicrobial activity, cytokine production and some aspects of macrophage involvement in sarcoidosis and idiopathic lung fibrosis. PMID- 7995402 TI - Bronchial necrosis and granuloma induced by the aspiration of a tablet of ferrous sulphate. AB - Aspiration of foreign bodies occurs mainly in children and elderly people. When the foreign body is a tablet, this event can be more severe due to the local release of active molecules. We observed spontaneously regressing bronchial necrosis and granuloma due to the aspiration of a tablet of ferrous sulphate. We stress the need to consider the possibility of aspiration of a tablet in elderly patients with acute respiratory symptoms, and the importance of an early removal of the tablet. PMID- 7995403 TI - Bacterial pseudomycosis: a rare cause of haemoptysis. AB - Pulmonary bacterial pseudomycosis, also referred to as botryomycosis, is a very rare, indolent illness that has been described mostly in patients with immunological problems. The histological appearance is similar to that of actinomycosis; however, various Gram-positive and Gram-negative bacteria have been implicated in the pathogenesis. We illustrate a rapidly progressive case of pulmonary bacterial pseudomycosis in a normal host whose presenting complaint was haemoptysis. PMID- 7995404 TI - Postinflammatory bronchiectatic cavity observed by fibreoptic bronchoscopy. AB - A 55 year old female, complaining of bloody sputum and fever, was referred to our institution. The chest roentgenogram on admission revealed a large thin-walled cavitary shadow in the right upper lobe. We could clearly observe the inner surface of the postinflammatory bronchiectatic cavity in the right B3 bronchus by fibreoptic bronchoscopy. This is the first case in which interesting bronchoscopic findings of a bronchiectatic cavity could be directly observed. PMID- 7995405 TI - Descending necrotizing mediastinitis secondary to a retropharyngeal abscess. AB - A rare case of descending necrotizing mediastinitis (DNM) secondary to a nontraumatic retropharyngeal abscess is reported. Even in the era of antibiotics, the mortality of DNM is still around 40%. In spite of drainage of a localized neck abscess, and the administration of systemic antibiotics, the retropharyngeal abscess extended to the pericardial and pleural cavities. Several drainage procedures and thoracotomies were performed to treat the bilateral empyemas and purulent pericarditis. The patient was discharged on hospital day 52. Computed tomography was used to follow the progression of disease, and assess the efficacy of treatment. DNM is a very aggressive form of mediastinitis. The importance of proper mediastinal drainage, as well as the systemic administration of antibiotics, must be emphasized. PMID- 7995406 TI - A patient with fever and an abnormal roentgenogram. PMID- 7995407 TI - Home treatment for chronic respiratory insufficiency: the situation in Europe in 1992. The European Working Group on Home Treatment for Chronic Respiratory Insufficiency. AB - The search for improved quality of life and a reduction in health care costs is leading to the development of home treatment. The organization of home treatment for chronic respiratory patients in 13 European countries was evaluated at the end of 1992 by means of a questionnaire. Switzerland and the Association Nationale pour le Traitement A Domicile de l'Insuffisance Respiratoire Chronique (ANTADIR) in France maintain registers for patients on oxygen therapy, mechanical ventilation and sleep disorders. Sweden and Poland have a national register for patients receiving oxygen. In other countries, some information can be obtained from the National Health Service or the commercial provider. Oxygen concentrators are used preferentially in all countries except Italy, Denmark, Spain and The Netherlands. Home ventilator treatment is generally performed by volume-cycled ventilators. National prescription rules exist in some parts of Spain, Switzerland and Belgium. In other countries, such as Germany, prescriptions rely on recommendations elaborated by specialists or international guidelines. Service and equipment are provided by national organizations, health services, commercial companies or hospitals. Home supervision of the patient is performed by a nurse and/or a doctor and equipment maintenance by a technician. Important differences exist between countries in Europe in home treatment of chronic respiratory disease. Comparative analysis should help achieve uniform standards and provide a basis for future research. PMID- 7995408 TI - Latex-induced occupational asthma. PMID- 7995409 TI - Thyroid cancer: a multivariate analysis on influence of treatment on long-term survival. AB - Contemporary management of patients with follicular pattern thyroid cancer remains uncertain. This retrospective multivariate analysis studied 410 such patients treated in a cancer hospital in the years 1932-72 and providing a follow up of 20 years. In papillary carcinoma thyroxine administration (P < 0.005) and surgery (P < 0.001) improved survival together with youth (P < 0.001) and being female (P < 0.05). In follicular carcinoma, thyroxine therapy (P < 0.001) increased survival as did surgery but it failed to reach significance (P = 0.19); increasing age (P < 0.001), stage M1 (P < 0.05) and 'complete' radiotherapy (P < 0.05) decreased survival. In anaplastic carcinoma survival was improved by thyroxine therapy (P < 0.001), a new finding, but decreased by stages T3 (P < 0.001) and M1 (P < 0.05); however, radiotherapy, the mainstay in control of local disease, did not increase survival. Overall, total thyroidectomy reduced local recurrence with an increase in complications and no operation gained a significant increase in survival. Radio-iodine achieved no benefit in survival which raises the possibility of confounding. Thyroxine therapy is indicated as initial treatment of follicular cell thyroid cancer. PMID- 7995410 TI - Interleukin 2 treatment in colorectal cancer: current results and future prospects. AB - Recent interest in the treatment of advanced colorectal cancer with immunotherapy has focused on the use of recombinant interleukin 2 (rIL2). These studies have shown that rIL2 used alone, in combination with lymphokine-activated killer (LAK) cells or tumour-infiltrating lymphocytes (TILs), has little anti-tumour activity, with low, short-lived clinical responses being documented. However, phase I and II studies evaluating rIL2 in combination with 5-fluorouracil (5FU) or 5FU and leucovorin (LV) have been more encouraging, with response rates of up to 46% being reported. Only one randomized, controlled study, however, has compared rIL2 combined with 5FU/LV vs 5FU/LV alone. Although there was no difference in tumour response rates between the two groups, there was a doubling in the median survival of those patients in the poor performance status group (ECOG 1). Also, studies have evaluated the effects of rIL2, given in the peri-operative period, on reversing the immunosuppression that occurs following 'curative' resection for colorectal cancer. These studies have shown an abrogation of immune suppression induced by surgery and an enhancement of host anti-tumour defence mechanisms in the peri-operative period, a time when active tumour dissemination has been shown to occur. These results may have important implications for the management of those patients with malignant disease who are undergoing major curative surgery. PMID- 7995411 TI - Primary small bowel malignant tumors. AB - We reviewed 69 patients who underwent surgery for primary malignant tumors of the small bowel over a 15-year period. Patients with periampullary lesions were excluded, as were those with known adenocarcinomas in other sites. There were 46 males (67%) and 23 females (33%) with an average age at presentation of 52.6 years (range 4-92). Of the 69 patients, four (6%) were asymptomatic. The mean duration of symptoms before diagnosis, in the remaining 65 symptomatic patients, was 3.6 months (range 1 day 1.2 years). The most frequent symptom was abdominal pain (83%), followed by nausea and/or vomiting (54%), and weight loss (43%). Abdominal mass was the most common finding on physical examination (29%), followed by abdominal distension (24%) and abdominal guarding and rigidity (14%). Laboratory examinations were normal in 26 patients (40%). Radiographic study of the duodenum and small bowel was abnormal in 87%. The diagnosis was suspected preoperatively in 51%. Lymphoma was the most common tumor (42%), followed by adenocarcinoma (38%), carcinoid (10%) and leyomiosarcomas (10%). In 41% the neoplasm was located in the jejunum, in 33% in the ileum, in 22% in the duodenum and in 4% multiple sites were found. Lymph node metastases were found in 45% and vascular invasion was found in 19%. Of the 65 symptomatic patients 43% presented as surgical emergencies, the rest had elective surgery. 61% had a curative resection, the rest were palliative or a bypass. The operative mortality rate was 10% and the morbidity rate was 24%. Ten patients underwent emergency surgery, developed a complication, giving a morbidity rate of 32% in this group. The 5 year overall survival was 43.25%. The 5-year survival for carcinoid tumors was 60% while the 5-year survival for small bowel malignant lymphoma and adenocarcinoma was 40 and 34.28% respectively. PMID- 7995412 TI - Size isn't important; the Forrest Unit. AB - The early success of breast screening in the UK is encouraging, and has been achieved by cooperation between multidisciplinary teams working together in large screening units. Future market forces may serve to disintegrate this arrangement with the resulting emergence of smaller, self-sufficient units. Winchester's 'first round' screening results suggest that with appropriately trained team members, such units can provide a convenient, high quality local service without compromising cancer detection. PMID- 7995413 TI - The value of ultrasound in the evaluation of palpable breast tumours: a prospective study of 400 cases. AB - In a prospective study, 400 palpable breast tumours were examined to establish the value of ultrasound. 174 Carcinomas were diagnosed by histological examination. The sensitivity of ultrasound examination in detecting malignancy was 96.6%, the specificity 94.2%. Ultrasound examination of a palpable breast tumour is reliable in differentiating between benign and malignant tumours. PMID- 7995415 TI - Curative endocavitary irradiation of small rectal cancers and preoperative radiotherapy in T2 T3 (T4) rectal cancer. A brief overview of the Lyon experience. AB - The aim of this study was the analysis of 414 patients treated by endocavitary irradiation for small T1 (T2) infiltrating adenocarcinomas between 1951-93 and of 337 patients treated by preoperative radiotherapy for T2 T3 (T4) rectal cancer, between 1978-92. Endocavitary irradiation was delivered with Papillon's technique using the PHILLIPS RT-50 machine. Preoperative external beam radiotherapy was given to the posterior pelvis only with an accelerated schedule of 39 Gy in 13 fractions over 18 days. Endocavitary irradiation with the use of intra-rectal ultrasound for patient selection resulted in a local control rate of 91% with no complication even in the medically inoperable patients. Preoperative external beam radiotherapy followed by radical resection resulted in a 90% pelvic control rate. Sphincter-sparing surgery was possible in 60% of patients with low or middle rectal lesions. PMID- 7995414 TI - Surgical pitfalls after preoperative chemotherapy in large size breast cancer. AB - Preoperative chemotherapy in 226 women with large breast cancers reduced tumour size sufficiently for breast conservation surgery, according to our criteria, in 203 patients (90%). After 50 months' mean follow-up there were 13/203 local relapses (5.3%). This approach is therefore effective but only if the breast can be conserved with good aesthetic result, otherwise mastectomy plus reconstruction is preferable. The type of surgery must be decided during operation after careful assessment of tumour regression, resection margins, tumour size in relation to breast size and extent of microcalcifications. PMID- 7995416 TI - Is the binding of mistletoe lectins I and III a useful prognostic indicator in colorectal carcinoma? AB - A retrospective study on 127 patients with colorectal carcinoma was performed to evaluate the use of mistletoe lectins I and III as possible prognostic indicators. Tissue sections were stained by a histochemical technique using these lectins and the staining results correlated with survival. No correlation between survival and the presence of lectin binding or non-binding was found. A lectin with the same monosaccharide specificity as ML-III, Helix pomatia agglutinin, which was of prognostic significance in the same patient cohort in another study showed on Western blot analysis a slightly different lectin binding pattern towards glycoproteins than the MLs. The results of this study indicate that even subtle differences in the carbohydrate composition of glycoconjugates which can be differentiated by lectins are of biological significance in terms of the metastatic spread of tumours. PMID- 7995417 TI - Taxotere inhibits in-vitro growth of human colonic cancer cell lines. AB - Taxotere a semisynthetic analogue of taxol, is prepared from a precursor extracted from needles of the tree, Taxus baccata. It is a mitotic spindle poison more potent than taxol, that increases the rate of microtubule assembly and inhibits depolymerization of microtubules. There has been little research on its effects on colorectal cancer. Five colorectal tumour cell lines were investigated using three modes: flow cytometry (to determine how Taxotere affects the cell cycle), MTT assay, (to examine the cytotoxicity of the drug), and measurement of tritiated thymidine uptake, (to see whether Taxotere affects the rate of DNA synthesis and cell turnover). A time-course experiment, using flow cytometry, showed effects beginning between 0 and 2 hours after exposure. 24-hour assays were conducted for flow cytometry, and showed large changes, arresting most cells in G2/M phases (e.g., cell line LIM 1215 exposed to 1 x 10(-6) M Taxotere showed 72% of cells in G2/M compared to 14.7% in controls). 24 and 48 hour assays were conducted for MTT and measurement of tritiated thymidine uptake. MTT showed significant inhibitory effects, with maximum inhibitions varying between 5 and 70% for different cell lines after 48 hours (P < 0.05), while uptake of tritiated thymidine was not altered. While Taxotere has dose-limited toxicity, our results suggest that many human colonic cancers will be sensitive to Taxotere. PMID- 7995418 TI - Management of large malignant rectal polyps with transanal endoscopic microsurgery. Is there anything better for the patient? AB - The authors report their experience with transanal endoscopic microsurgery (TEM), a technique that allows all the standard surgical manoeuvres such as tissue excision, suction, control of bleeding and suturing in the entire length of the rectal cavity. Main indications for TEM are the removal of large sessile polyps and early rectal cancers' (T1, G1-G2). Out of 50 patients submitted to TEM the authors consider in this study 24 cases with a preoperative diagnosis of benign large sessile polyps. The procedures included: 14 (58.3%) total wall excision, four (16.6%) total wall excision with perirectal fat, three (12.5%) mucosectomy, one mucosectomy + total wall excision, one partial wall excision + total wall excision, and the remaining case was converted to laparotomy due to a large intraperitoneal perforation. There was no operative mortality and an 8.3% rate of major complications. With a median follow up of 19 months there was no evidence of local or distant recurrence. The authors compare their results with those of alternative endoscopic and surgical techniques and highlight the advantages of TEM in the management of large and giant rectal polyps. PMID- 7995419 TI - Genetic rearrangements in sporadic and familial gastric carcinomas detected with microsatellite markers. AB - Ten gastric carcinomas were studied for loss of heterozygosity by analysis of 21 microsatellite markers from 14 different chromosomes. Four patients had a family history of gastro-intestinal cancer, and six tumours were considered sporadic. We also studied a new mechanism in tumourigenesis recently reported in hereditary non polyposis colon cancer, a defect in mismatch repair that is seen as gain of new bands by the use of dinucleotide repeat markers. Loss of heterozygosity was detected with two markers in one primary tumour and with the majority of markers in one metastasis from a sporadic gastric tumour. Gain of microsatellite bands was seen in one tumour from a gene carrier in a family with hereditary non polyposis colon cancer and in one sporadic tumour. Two tumours from patients with a family history of gastric cancer showed no rearrangements. Our results suggest that different types of genes are involved in initiation and progression of gastric cancer in sporadic and familial gastric cancer. PMID- 7995420 TI - Intraluminal irradiation in the treatment of malignant airway obstruction. AB - A group of 79 patients with non-resectable lung carcinomas (T1, 1; T2, 13; T3, 34; T4, 19; recurrence, 12) underwent endobronchial iridium-192 high-dose rate afterloading therapy (5 Gy/session total dose: 5-25 Gy, mean 11.6 Gy). In 39 cases the fair general condition and absence of metastases allowed external-beam irradiation (EBR) to be administered (50-70 Gy total dose; 2gy/day), starting 1 week after the brachytherapy session. In nine cases with superior vena cava syndrome, EBR (30 Gy total dose; 3 Gy/day) was administered concomitantly. Improvement in symptoms of respiratory obstruction was noted in 87% of our patients. The mean duration of palliation was 17.1 weeks in the group without and 34.7 weeks in that with additional EBR. The median survival time was 6 months without and 13 months with additional EBR. In T4 cases EBR had no impact on the 1 year survival (30.8% vs 24.4%, P > 0.05). The rate of severe complications was 7%, without significant differences between cases with or without EBR. PMID- 7995421 TI - Long-term neuropathy after regional isolated perfusion with melphalan for melanoma of the limbs. AB - The incidence of long-term (> or = 3 months) neuropathy in 350 melanoma patients treated with single normothermic or 'mild' hyperthermic perfusion with melphalan in the period 1978 to 1990 was studied. Long-term neuropathy was encountered in 14 patients; in 10/51 patients (20%) after perfusion at the axillary level and in 4/247 patients (2%) after perfusion at the iliac level. After brachial and femoro popliteal perfusions no long-term neuropathy was observed. Neuropathy, mainly consisting of paresis/paralysis of the hand and/or fingers, anaesthesia, and/or paraesthesiae, improved over a mean period of 16 (3-43) months in eight patients, but three patients still had serious neuropathy one year after perfusion. In another six patients little improvement was seen and four died with permanent neuropathy. Acute regional toxicity after perfusion and the application of 'mild' hyperthermia did not seem to influence the incidence of long-term neuropathy. This complication is probably a result of the isolating Esmarch rubber bandage being applied too tightly during perfusion at a proximal level. At the axillary level, where the brachial plexus lacks the protection from enveloping tissues, nerve damage is especially prone to occur. We recommend applying this bandage no tighter than is necessary to maintain the isolation of the circuit. This implies meticulous surgical isolation of the vascular system and accurate monitoring of leakage. PMID- 7995422 TI - Use of the biomedicus pump in resection of renal carcinoma invading the vena cava. AB - The authors report a 7-year old boy suffering from a renal carcinoma with a tumoral thrombus invading the vena cava. The kidney and the tumoral thrombus were removed with the help of a Biomedicus pump. This paper shows how to avoid a cardiopulmonary bypass procedure in order to perform safely a tumoral thrombectomy with this relatively new technique. PMID- 7995423 TI - De-epithelialized latissimus dorsi musculocutaneous flap to reconstruct major chest wall resection after breast carcinoma. AB - Two cases of chest wall reconstruction after major resection due to breast carcinoma were reported. De-epithelialized latissimus dorsi musculocutaneous flaps were inserted in the skeletal defect in order to protect the underlying tissue and stabilize the thorax. The de-epidermized skin was anchored to the ribs and the sternum. The interest of this autologous procedure was discussed in relation to prosthetic reconstruction. Ease of use, flexibility and resistance to infection were underlined. PMID- 7995424 TI - Pain in the distribution of the femoral nerve: early evidence of recurrence of a retroperitoneal sarcoma. AB - Pain in the distribution of the femoral nerve following resection of a retroperitoneal sarcoma may signify tumor recurrence and should require exploration of the nerve to its origin from the spine in order to rule out a small, undetectable recurrence by CT scan. PMID- 7995425 TI - Occult papillary carcinoma of the thyroid presenting as an intratracheal tumour. AB - A case of occult papillary carcinoma of the thyroid presenting as an intratracheal tumor in a 64-year-old woman is reported. No lymph node metastases were observed. The patient had an 11-year history of hoarseness, dyspnea and productive cough, and was found at bronchoscopy to have a large intratracheal tumor occupying half of the lumen. It was histologically a papillary carcinoma with immunoreactivity of thyroglobulin. No primary tumor was found in the thyroid gland. By reviewing the English literature, no similar case was encountered. PMID- 7995426 TI - Adenocarcinoma of the rectum with a solitary metastasis to the urethra in a female. AB - Adenocarcinoma of the urethra is extremely rare, constituting 10 to 20% of all primary urethral malignancies in women. As in men, the squamous carcinoma accounts for 70% of all urethral tumours. Adenocarcinomas are mostly primary lesions, originating from the paraurethral glands. A case is reported about a female patient, presenting with a mucinous urethral adenocarcinoma, presumably secondary to a primary rectal adenocarcinoma. PMID- 7995427 TI - Long-term disease-free survival after isolated peritoneal metastasis from colonic cancer. AB - We present the case of a 29-year-old female patient with an isolated peritoneal metastatic mass in the Douglas pouch, following ileocecal resection for a Dukes C2 colon cancer of the caecum. As initial treatment, four courses of continuous infusion with epiadriamycin were administered. The effect on the tumour size was marginal. Palliative radiotherapy (33 Gy) resulted in a reduction of the tumour size and subsequently a wide posterior exenteration could be performed. Five years after the initial diagnosis the patient is still in good health with no evidence of tumour recurrence. We sincerely believe that a maximum effort aiming for cure is warranted in selected patients with localized residual or metastatic peritoneal colon cancer, even if the initial prospects seem less favourable. PMID- 7995428 TI - Benign giant cell tumour of bone in a child with pulmonary metastases at presentation. AB - The clinical course of a 14-year-old boy who presented with a giant cell tumour of bone with pulmonary metastases is reported. There was a partial response to chemotherapy which included vincristine, adriamycin, ifosfamide, carboplatinum and etoposide. Two enlarging metastatic lung lesions were later resected because of chest pain, with symptomatic improvement. The patient is currently well almost 7 years from diagnosis despite the presence of radiological disease. PMID- 7995429 TI - Pilomatrix carcinoma: a case report and review of the literature. AB - Pilomatrix carcinomas are malignant uncommon tumors of hair matrix origin. The clinicopathologic features of a case of pilomatrix carcinoma are described and compared with those of the previously reported cases. Because these tumors behave similarly to a basal cell carcinoma, a complete excision is necessary in order to minimize the likelihood of relapse. PMID- 7995430 TI - How I do it--breast cancer. The psychological management of the patient with early breast cancer. PMID- 7995432 TI - Hygienists' creative marketing skills can benefit dentistry. PMID- 7995431 TI - Malignant solid tumours in childhood. PMID- 7995433 TI - High-technology equipment enhances practice marketing. PMID- 7995434 TI - Boosting your financial health. PMID- 7995435 TI - Emergency! PMID- 7995438 TI - Ten pearls that can increase profitability and productivity. PMID- 7995436 TI - Office is user-friendly for elderly, disabled. PMID- 7995437 TI - Increasing your practice revenues. PMID- 7995439 TI - Diastema closure utilizing porcelain veneers--simple and advanced. PMID- 7995440 TI - The concept bridge. PMID- 7995441 TI - A method for making predictable and highly accurate provisionals. PMID- 7995442 TI - Hollow pledges and the NHS. PMID- 7995444 TI - Development of new adhesive pulp capping materials. AB - The pulp capping materials currently available do not adhere to dentine but cover it and therefore extensive removal of tooth tissue is necessary to expose sufficient dentine for the adhesives used to secure the restoration (the adhesives do not adhere to the capping material). The authors describe how two new pulp capping materials have been developed, which combine the properties required for pulp capping with an ability to adhere to dentine. PMID- 7995443 TI - Restoration of the maxillary arch using implants, natural teeth and the Konus crown: a case study. AB - Restoring the maxillary arch by using a suprastructure retained by a Konus crown means that the patient can remove the crown for oral hygiene. This construction enables large embrasure spaces to be avoided without compromising phonetics, that is, without adversely affecting the patient's speech. It also enables the dental surgeon to monitor the tooth and implant abutments and the soft tissues around them. In this article we demonstrate successful restoration of the maxillary arch by the use of Konus crowns on a combination of implants and natural teeth. PMID- 7995445 TI - A computer-based orthodontic learning package: report of a trial. AB - Computer-based teaching has been used in the Department of Child Dental Health of the University of Bristol Dental School for almost 10 years to provide students with additional practice in the assessment of malocclusion and the planning of orthodontic treatment. In this article, the authors describe a study of the usefulness of computer-based learning packages for general practitioners and offer guidelines for others wishing to set up such a scheme. PMID- 7995446 TI - A nose stud retainer clip lost within the nasal cavity discovered on dental radiographs. AB - It is fairly common for a dental surgeon to come across patients with foreign bodies in the nasal cavity. In this paper we report an unusual case of a nose stud retainer clip being displaced into the nasal cavity by trauma, and its discovery on radiographs taken to assess dental injuries. We also present a review of the literature since 1982, and assess the possible sequelae to nasal foreign bodies. PMID- 7995447 TI - Review of a new root canal obturation technique. AB - The relatively new technique of obturation using Thermafil endodontic obturators is claimed by the manufacturers to use gutta percha of a more linear structure than conventional gutta percha, and so provide a seal at least equal to laterally condensed material. In this article the authors describe the practical use of this widely marketed technique. Studies which have so far evaluated this technique are reviewed and its advantages and shortcomings discussed. PMID- 7995448 TI - The one hundred million missing females are dead: let it happen never again. PMID- 7995450 TI - Discrimination against the female child. PMID- 7995451 TI - Female genital mutilation and the responsibility of reproductive health professionals. PMID- 7995449 TI - Women's health: an overview. PMID- 7995452 TI - Adolescent health: changing needs. PMID- 7995453 TI - Safe motherhood. PMID- 7995454 TI - Infertility: an international health problem. PMID- 7995455 TI - Contraception and women's health. PMID- 7995456 TI - Abortion and women's reproductive health. PMID- 7995457 TI - Reproductive tract infections. PMID- 7995458 TI - The threat of AIDS to the health of women. PMID- 7995459 TI - Women and cancer. PMID- 7995460 TI - Menopausal osteoporosis. PMID- 7995461 TI - Key issues affecting the status of women. PMID- 7995462 TI - Women's reproductive rights. PMID- 7995463 TI - Gender-based violence and women's reproductive health. PMID- 7995464 TI - Women in the medical profession and women's health. PMID- 7995465 TI - Women's health policy: where lie the interests of physicians? PMID- 7995466 TI - Issues in health care services for women. PMID- 7995468 TI - Special issue: World report on women's health. PMID- 7995467 TI - The role of FIGO in the promotion of women's health. PMID- 7995469 TI - Confirmation of Leinfelder clinical wear standards. AB - OBJECTIVES: Accuracy of composite wear studies based on Leinfelder standards has been disputed. There are differences with other well-calibrated systems such as the M-L and Vivadent wear standards. The objective of this study was to reevaluate the margin height at key regions along the restoration margins for each of the 6 Leinfelder standards using laser profiling techniques. METHODS: The Leinfelder standards were profiled in parallel paths 100 microns apart and measured in x-y-z position every 20 microns along those paths using a laser profilometer. RESULTS: Rounding of cavosurface enamel margins from intraoral wear greatly increased the uncertainty of the true enamel margin location and step height measurements, precluding unequivocal measurements for standards #2 and #3. Values for other standards for the original report, newly measured means and standard errors, and measured ranges were: #4 (322 microns, 333 +/- 34 microns, 171-507 microns), #5 (382 microns, 459 +/- 44 microns, 202-649 microns), and #6 (493 microns, 584 +/- 91 microns, 315-1022 microns). There were no statistically significant differences (p < or = 0.10) between these and original values. Large standard errors may have obscured small differences that may exist. The Leinfelder cast conversion scale seems to be the correct relative magnitude. SIGNIFICANCE: Differences between Leinfelder casts and other standards may be due to differences in shadow production. Clinical wear may be systematically underestimated by other cast evaluation methods that have well-defined margins. This emphasizes the need for standard casts with margin morphology similar to the clinical casts being evaluated for wear. PMID- 7995470 TI - Influence of prolonged thermal cycling and water storage on the tensile bond strength of composite to NiCr alloy. AB - OBJECTIVES: The purpose of this study was to evaluate the bond strength and bond durability of new adhesive systems (both micromechanical and chemo-mechanical) to a beryllium-free nickel-chromium alloy (NiCr). METHODS: Plexiglass tubes filled with composite were bonded to NiCr alloy discs. Groups of 24 samples were bonded using six different bonding systems. Subgroups of eight bonded samples were stored in an isotonic artificial saliva solution (37 degrees C) either for 1 d, 30 d or 150 d. In addition, the 30 and 150 d samples were thermal cycled for 7,500 or 37,500 cycles, respectively. RESULTS: The bond strength of a conventional BisGMA composite to sandblasted NiCr was statistically significantly lower than that of chemo-mechanical bonding systems and decreased continuously during the storage time of 150 d. The additional use of a silane on the sandblasted alloy resulted only in a slight, statistically insignificant increase in bond strength. Statistically significantly higher and more durable bonds to NiCr alloy were achieved either with the combination of silica coating and use of a conventional BisGMA composite or with the combination of sandblasting and the use of a composite modified with a phosphate monomer. In these systems, the bond strengths were limited by the cohesive strength of the resin composites. However, a newly developed composite containing the same active phosphate monomer showed a statistically significant decrease in bond strength (cohesive strength) over storage time. SIGNIFICANCE: Longer-term storage times in a wet environment are needed in laboratory tests to examine the durability of bonding systems. PMID- 7995471 TI - The effect of esthetic fibers on the flow properties of an acrylic resin denture base material. AB - OBJECTIVES: This study was conducted to measure the effect of viscose rayon esthetic fibers on the flow properties of an acrylic resin denture base material. METHODS: Two testing methods using a needle penetrometer and an oscillating rheometer were employed on weighed proportions (0.1%, 0.2%, 0.8%, and 0.3%) of fiber. RESULTS: The results show that the fibers affect the flow properties of the polymer/monomer mix. Increasing the percentage of fibers decreases the flow of the material and reduces the doughing time. With increasing amounts of fiber, a rapid increase in the viscosity occurs with a corresponding adverse effect on flow properties. SIGNIFICANCE: It is concluded that these properties are important for the successful handling of acrylic materials since they can influence the accuracy and quality of the molded denture. PMID- 7995472 TI - Behavior of a calcium phosphate cement in simulated blood plasma in vitro. AB - OBJECTIVES: The purpose of this study was to gain a better understanding of the integration of calcium phosphate cement (CPC) implants in biological tissue. METHODS: An in vitro continuous flow system was employed to examine the protracted behavior of disc-shaped specimens of this bioactive material under sustained physiological-like solution conditions. Weight measurement, diameteral tensile strength measurement (DTS), scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FTIR), and powder x-ray diffraction (XRD) were used to characterize the CPC samples as a function of immersion time. RESULTS: When CPC was immersed in simulated blood plasma in which the Ca (2.5 mmol/L) and inorganic phosphate (1.0 mmol/L) levels were kept constant, both the weight and DTS of the specimens steadily increased to about 1.5 times their original values over a period of 20 wk. SEM observations showed new precipitate formations in intimate contact with the original CPC surface. FTIR and XRD analyses revealed that the precipitate was a B-type carbonate hydroxyapatite (OHAp), the type of OHAp observed in bone and dentin. On the other hand, the interior of CPC discs did not show an increase in either bulk density or OHAp content. Thus, the increases in weight and DTS are attributable to the OHAp precipitation on the CPC surface. SIGNIFICANCE: The results suggest that under in vivo conditions, CPC implants would not dissolve in physiological fluids. OHAp coatings may form on the implants, which may enhance bonding of implants to bone by mechanically strengthening the interface between them. PMID- 7995473 TI - The effects of peroxide bleaching on composite to enamel bond strength. AB - OBJECTIVES: The objective of this in vitro study was to evaluate the effects of an in-office type of bleaching regimen on the composite to enamel bond. METHODS: The enamel on forty extracted human teeth was subjected to a 25% hydrogen peroxide bleaching treatment. Ten additional unbleached specimens served as controls (Group A). The 40 bleached specimens were divided into four equal groups (Groups B-E). Composite cylinders were bonded to the prepared surfaces at various time intervals following bleaching. Group B was bonded immediately, Group C at 1 d, Group D at 1 wk, and Group E at 1 mon post-bleaching. RESULTS: Mean shear bond strength values showed a significant decrease in bond strength for Group B. However, the bond strength returned to normal values after 1 d and remained normal for at least 1 mon. Scanning electron microscope examination showed an apparent decrease in the number of resin tags present in the enamel/composite interface for Group B compared with the other groups including controls. SIGNIFICANCE: Polymerization inhibition of the resin bonding agent is the likely mechanism for the effects of the bleaching on bond strength. PMID- 7995474 TI - Mechanical behavior of glass ionomer cements affected by long-term storage in water. AB - OBJECTIVES: The early strength of glass ionomer cements was investigated previously (Cattani et al., 1993). Using the same set of glass ionomer cements, this study was designed to determine if mechanical property degradation occurred after an extended period of storage in water. METHODS: In the present study, the effect of aging in water on the compressive, tensile and flexural strengths of twelve commercial glass ionomer cements was evaluated at different time intervals after the beginning of the setting reaction. The aging periods varied from 24 h to 12 mon. RESULTS: The results show that the mechanical properties of the tested materials are in some cases affected by long-term aging in water. The evolution of strength follows distinct patterns of change. It has been established that the glass ionomer cements are neither characterized by a continuous increase nor a continuous decrease in strength. Most of the materials tested maintained a constant strength. However, several of them first display an improvement of the mechanical strength followed by a reduction. In this case, the 24h and the 12 mon strengths are usually similar. SIGNIFICANCE: The aging mechanisms of glass ionomers are complex. Strengthening probably results from additional crosslinking and build-up of a silica gel phase, whereas weakening may result from erosion and plasticizing effect of water. PMID- 7995476 TI - The effect of water on polymer matrix and composite wear. AB - OBJECTIVES: Previous studies have demonstrated increased in vitro wear of composite after long-term water exposure. The increased wear effect was not clearly related to debonding of the filler from the matrix, resulting in accelerated loss of filler particles. The hypothesis tested in this experiment was that the changes in in vitro three-body wear of a composite following water storage are caused by changes in the wear resistance of the polymer matrix. METHODS: In the in vitro wear test used, a specimen wheel was rotated against an antagonist wheel in a slurry of millet seed and water. Specimens were fabricated of composite and polymer matrix only. Specimens were wear tested after 1 wk of ambient temperature dry storage and after 14, 20, and 26 mon of water storage at 37 degrees C. RESULTS: The wear of the composite significantly increased (23%) during the 26 mon of water storage. The wear of the polymer specimens increased slightly; however, the increase was not statistically significant. SIGNIFICANCE: Analyses of the data using a series model for the wear of a composite indicated that the increase in wear of the composite was not due to changes in the wear resistance of the polymer matrix. Instead, the increased composite wear was more likely due to increases in the dislodgment rate of filler particles and the wear rate of the filler itself. PMID- 7995475 TI - Guidelines for experimental studies. AB - OBJECTIVES: The purpose of this document is to present guidelines for the training of researchers and for the planning of experiments that ensure optimum interaction and communication among the investigators and statisticians of the research team. METHODS: The protocol described in this document is designed to systematically guide a researcher through a sequence of planning steps and checkpoints to ensure proper experimental design, data management, statistical analyses, and interpretation. RESULTS: The investigator and the statistician, as a collaborative team, will be able to determine the most effective and appropriate procedures and tools necessary for the successful completion of a research project. SIGNIFICANCE: Planning an experimental study necessitates much thought. Lack of essential communication with a statistician in the initial stages of the experimental design can doom the experiment to failure. Flawed research studies may be associated with one or more of the following: failure of the established testable hypothesis, uncontrolled biases, insufficient sample size, lack of appropriate controls, variability in specimen preparation, improper calibration of instruments or standardization of measurements, incorrect data entries, inappropriate statistical analyses, errors in interpretation of statistical analyses, and erroneously drawn conclusions. Standard guidelines will eliminate many of these potential problems. PMID- 7995477 TI - Moduli of rupture of layered dental ceramics. AB - OBJECTIVE: The purpose of this study was to determine the moduli of rupture of layered beams made of strong core materials veneered with weaker conventional feldspathic porcelain. METHODS: A three-point flexural test, and formulae derived especially for this purpose were used. Two systems were investigated. The first consisted of Vitadur N (Vita Zahnfabrik), a conventional feldspathic porcelain; and Dicor MGC (L.D. Caulk), a machinable glass ceramic. The second consisted of Vitadur N and In-Ceram (Vita Zahnfabrik), a strong reinforced aluminous porcelain. RESULTS: Two-way ANOVA and Tukey tests were used to evaluate the effect of numerous factors on the modulus of rupture. The results indicated that the material forming the tensile surface, the material forming the compressive surface and their interaction had a highly significant effect on modulus of rupture (p < 0.05). The effect of the material forming the tensile surface on modulus of rupture was of much greater magnitude than that of the compressive surface. Theoretical curves describing effects of the layers' elastic moduli and thickness on the force-bearing capacity of model beams were plotted. These indicated that for a wide range of thickness ratios and for a wide variety of elastic modulus ratios, the tensile material dominates the force-bearing capacity of layered beams except when a very much lower modulus material forms the compressive layer. SIGNIFICANCE: Layered prostheses made of strong cores veneered with weaker feldspathic porcelain may be prone to failure when the feldspathic surfaces are subjected to tensile force. PMID- 7995478 TI - Review of the 1993 dental materials literature. AB - OBJECTIVES: Electronic databases are not sufficiently up to date to provide comprehensive notation of the most recent literature for reference in developing scientific papers. The objective of this summary was to identify and categorize the 1993 dental materials scientific literature that dealt with restorative dentistry. METHODS: 17 primary journals were manually searched via the tables of contents, and 101 secondary journals were manually or electronically searched. Dental materials citations were categorized into 15 major sections and several subsections, excluding case reports and all the literature primarily related to dental implants or biomedical materials outside of dentistry. RESULTS: This study identified 786 citations, the largest number being associated with glass ionomers and composites. SIGNIFICANCE: This citation list provides a comprehensive source for review by academicians and researchers that bridges the gap between initial publication and electronic citation. PMID- 7995479 TI - An esthetic glass-ceramic for use in composite restoration inserts. AB - The objective of the preliminary work reported here was to prepare an improved formulation of intrinsically colored microcrystalline glass-ceramic. Applications could include "megafillers" for direct composite restorations, precision castings, and CAD-CAM prostheses. The experimental glass-ceramic reported here contained SiO2 56.9, AI2O3 19, LiO2 7, ZnO 6, MgO 5, TiO22, ZrO22, P2O52, and CeO20.1 mole%. The batch materials were melted and stirred at 1,610 degrees C for 2 h, quenched in water and also formed into a block of a clear, slightly yellow glass. To identify the crystalline phases that developed during transformation of the glass to the ceramic, x-ray diffraction was used on ten aliquots taken during 15 h of stepwise heating from 750 to 1050 degrees C. With heating, the yellow color deepened to a very translucent "dark yellow" dental shade, then lightened with gradually increasing opacity during formation of secondary crystalline phases. X-ray opacity was approximately equivalent to that of dental enamel. The refractive index of the glass, nD1.554, increased during nucleation and growth of the crystalline phases to a maximum of 1.586. Intrinsic coloration of these glass ceramic materials can be controlled by varying the heat treatment and/or composition to match typical dental shades. PMID- 7995480 TI - In vitro bond strength of two adhesives to enamel and dentin under normal and contaminated conditions. AB - In vitro bond strengths of human enamel and dentin treated with five contaminants were measured with air, water and damp conditions as controls. Two commercial bonding agents (a lower-viscosity, solvent-containing type, AB, and a higher viscosity, hydrophilic monomer type, SB) and their composites were applied to tooth structure under two conditions (contaminated and re-etched). Samples were debonded in tension after 24 h using an inverted, truncated cone test. Among the controls, the highest bond strengths were obtained with damp conditions for AB (24 MPa) and damp conditions or air for SB (22 MPa) with small differences between enamel and dentin. Most contaminants lowered the bond strength. Re etching without additional mechanical preparation resulted in bond strengths similar to controls. Bond strengths to tooth structure with the bonding agents tested may be less sensitive to common forms of contamination than typically assumed. PMID- 7995481 TI - Enhanced evaporation of mercury from amalgams in non-oxidizing environments. AB - The release of mercury from two freshly triturated amalgams exposed to a reducing atmosphere, hydrogen, was quantitated at three different temperatures. A low copper and a high-copper amalgam were placed into a flowing hydrogen gas atmosphere for 60 min after trituration, and then the hydrogen was replaced by compressed air. The results were compared to those obtained in a previous study in which air and argon atmospheres were used under identical conditions. At 37 degrees C, the rate of evaporation of mercury from the amalgams was similar when they were exposed to hydrogen before being exposed to air. During exposure to hydrogen, the evaporation rate appeared to exceed the limit of the gold film mercury analyzer (284 pg/mm2/s), but was rapidly reduced upon exposure to air. The results were identical to those from argon exposure. When the same experiment was performed at 80 degrees C, the evaporation rate after hydrogen exposure was greater than that after exposure to argon, and far greater than that during exposure to air alone. Similar results were achieved at 110 degrees C, but there was less difference between hydrogen and argon exposure. The results support previous studies which show that the evaporation of mercury from amalgam is mainly limited by the formation of an oxide film. PMID- 7995482 TI - Microleakage of resin-modified glass ionomer cement restorations: an in vitro study. AB - Microleakage of two resin-modified glass ionomer cement (GIC) restorative materials was compared with that of two conventional GIC restorative materials. Forty-five noncarious extracted human molars were prepared with standardized Class V cavity outlines on the buccal and lingual surfaces. The occlusal margin was in enamel and the gingival margin was in dentin/cementum. All were restored according to the manufacturers' instructions. After thermocycling, 30 teeth were placed in 2% basic fuchsin dye for 24 h, sectioned and viewed with a stereomicroscope to assess microleakage. The other 15 teeth were sectioned, replicated and prepared for marginal gap evaluation using a SEM. Differences in microleakage scores between materials were compared using Kruskal-Wallis and Mann Whitney U tests. One resin-modified GIC restorative material showed significantly less microleakage against enamel and dentin/cementum compared to the conventional GIC restorative (p < 0.01). Marginal gap formation for both resin-modified GIC restorations was limited to the axial wall of the restorations. PMID- 7995483 TI - Microbial accumulation and vitality on different restorative materials. AB - A new technique using standardized test facings was designed to evaluate interdental plaque accumulation on different restoration materials. In 10 volunteers, a total of 40 samples, including enamel, two different ceramics and a bonding composite, were inserted one by one into a precision attachment in an experimental inlay bordering on either the lower second premolar or the lower first molar. Bacterial accumulation on each approximal specimen was allowed to mature for 3 d. Following microbiological processing of the plaque samples, total bacterial counts, colony forming units and the bacterial vitality were determined. The results revealed different accumulation rate patterns. Both ceramics accumulated less plaque with a reduced vitality compared to enamel, while the bonding composite showed no significant differences compared to the natural tooth substance. No significant differences were detected when comparing the two examined ceramics. PMID- 7995484 TI - Determination of the degree of cure of dental resins using Raman and FT-Raman spectroscopy. AB - FT-IR spectroscopy has traditionally been used to determine the degree of conversion of dental resins. FT-Raman scattering provided an alternate method of obtaining degrees of conversion for these systems and was particularly useful for measuring spectra of materials without any sample preparation. Raman and FT-Raman spectroscopy gave identical results, but the latter technique was preferred for the highly fluorescent samples often encountered in commercial composites. Linear calibration curves were obtained for the aromatic mixtures Bis-GMA/TEGDMA and Bisphenol-A/TEGDMA using C = C/phi, and for the wholly aliphatic mixture EGDMA/EGDA using C = C/C = O, over a wide range of mole ratios. If both the mole and intensity ratios [C = C/phi or C = C/C = O] were known for an uncured dental resin, then the degrees of conversion could be obtained for the cured materials using Raman spectroscopy. However, if the mole ratios for the uncured resin were unknown, then the degree of conversion depended on the calibration curve, since the Raman scattering cross section of the vibrational modes depended on the molecules to which they were attached. PMID- 7995485 TI - Softening patterns of post-cure heat-treated dental composites. AB - The softening of post-cure, heat-treated dental composites in various solutions was evaluated by Knoop hardness measurements. The samples were heated at 120 degrees C for 7 min immediately after curing and immersed in various solutions, water, ethanol, heptane and 0.1 N NaOH. Significant increases in hardness were observed for heated samples when compared to unheated samples. The various solutions softened both heated and unheated composites but heated samples were softened to a lesser degree. Plots of hardness of heated and unheated samples were nearly parallel, indicating that mechanisms such as penetration of the resin matrix, degradation of the silane coupling agent and fillers may be involved in the softening of both heated and unheated composites. Post-cure heat treatment improved the resistance to softening of dental composites. PMID- 7995486 TI - Loss of enamel due to etching with phosphoric or maleic acid. AB - In this study, the effect of enamel etching resulting in permanently lost enamel was investigated. Phosphoric acid and maleic acid were used as etchants. Also the etch duration was varied. The results of the study show that phosphoric acid removed significantly more enamel than maleic acid. The relationship found between the loss of enamel and the etch duration suggested that a diffusion controlled mechanism plays a role in the case of both acids. Morphological information obtained by scanning electron microscopy indicated that the surface structure resulting from etching with phosphoric acid and maleic acid is similar. PMID- 7995488 TI - [Recovery time from myocardial ischemia induced by exercise test: correlation with duration of ischemia during the test and with the extent of coronary disease]. AB - BACKGROUND: Aim of this study was to evaluate the factors affecting the duration of the recovery time (RT) after a positive exercise stress test and to define its relationship with the extent of coronary artery disease (CAD). METHODS: We studied 109 consecutive patients with a positive exercise test and proven coronary disease. RESULTS: RT was neither related to the severity of CAD, nor to exercise duration, rate-pressure product at the end of the exercise and maximum ST segment depression. A significant linear relationship was found between RT and the time of ischemia during exercise (IT) (r = 0.66, p < .001). This relationship was analyzed separately in patients (pts) with advanced (Group I) and in pts with less severe CAD (Group II). The regression line of the data showed a similar slope but a higher y-axis intercept in Group I than in Group II (p < .05). The RT/IT ratio was in fact significantly higher in Group I than in Group II (3.0 +/- 1.3 vs 1.7 +/- 0.7, p < .0001). Discriminant analysis was performed to predict the presence of advanced CAD: using the RT/IT ratio instead of RT correct classification rate of the model increased from 81.4 to 86.7%, predictive accuracy from 73.7 to 85.3% and true negative rate from 85.3 to 87.4%. CONCLUSIONS: These results suggest that the normalization of the recovery time by time of ischemia during the test provides a simple and useful index for the prediction of the extent of coronary artery disease. PMID- 7995487 TI - [Quality assurance and cost control in invasive and interventional cardiology]. AB - We report our experience of Quality Assurance in a Cardiac Catheterization Laboratory of the National Health Service. An attempt was made to apply these criteria to the medical activities as well as to the management and economic aspects of our work. Limits and perspectives of this experience are discussed as a contribution to ongoing debate among cardiologists and public health Authorities. PMID- 7995489 TI - [Plasma levels of basal beta-endorphin and after effort in patients with severe left ventricular dysfunction and heart failure]. AB - BACKGROUNDS: Purpose of the study was to evaluate beta-endorphin plasma levels at rest and after exercise, and the beta-endorphin release, in relation to exercise capacity, in patients with severe left ventricular dysfunction and heart failure. METHODS: Beta-endorphin plasma levels were assayed by radio-immunoassay before and after cardiopulmonary exercise testing in 28 heart failure patients with radionuclide ejection fraction < 35%, left ventricular end-dyastolic dimension > 60 mm and heart failure, and in 9 age-matched normal subjects. According to Weber's classification, 10 patients were in class A, 9 in class B, and 9 in class C. RESULTS: Beta-endorphin plasma levels at rest were respectively 3.52 +/- 2.31 pmol/L in patients, and 1.77 +/- 0.84 pmol/L (p < 0.05) in normals. In patients, baseline beta-endorphin correlated to VO2max (r = -0.76), peak rate-pressure product (r = -0.60) and exercise time (r = -0.56), then progressively increasing from class A to C. After exercise, beta-endorphin plasma levels increased respectively to 6.42 +/- 3.44 pmol/L (p < 0.001 vs baseline) in patients, and to 5.46 +/- 2.14 pmol/L (p < 0.001 vs baseline and NS vs patients) in normals. In patients, the release during exercise of beta-endorphin (exercise - baseline/baseline x 100) correlated to VO2max (r = 0.82), peak rate-pressure product (r = 0.64) and exercise time (r = 0.55), then progressively decreasing from class A to C. At multivariate analysis beta-endorphin release showed the greater correlation to exercise capacity parameters. CONCLUSIONS: In heart failure patients, beta-endorphin plasma levels are elevated at rest and its release during exercise is reduced in relation to functional impairment. PMID- 7995490 TI - [Do our patients follow the clinical indications prescribed after coronary angiography?]. AB - BACKGROUND: Aim of the study is to evaluate patients compliance with therapeutic recommendations after coronary angiography. METHODS: We analyzed all patients who underwent coronary angiography in an university center during 1990. One of the following treatments were recommended: medical therapy without revascularization, percutaneous transluminal coronary angioplasty, coronary artery bypass grafting. A cohort of 392 patients was assessed one year after coronary angiography in order to evaluate clinical predictors of non compliance with the treatment recommended. RESULTS: Of the 141 patients, for whom medical treatment was recommended, 16 (11%: 95% confidence interval 6-17%) had revascularization. By stepwise discriminant regression analysis, older age, congestive heart failure and critical lesion of the left anterior descending artery were statistically significant predictors of non compliance. Of the 137 patients, for whom PTCA was recommended, 8 (6%: 2-9%) were non compliant. No variables were predictive of non compliance. Of the 114 patients, for whom CABG was recommended, 15 (13%: 7-19%) were non compliant. By stepwise regression analysis, absence of typical angina was predictive of non compliance. For 12 patients non compliance was related to personal preferences, for 10 to clinical deterioration, for 9 to a second opinion, and 3 were still in the surgical waiting list one year after coronary angiography. One year mortality was not affected by non compliance. CONCLUSIONS: Non compliance to recommended treatment after coronary angiography is uncommon and is mainly related to patients preference towards a less invasive treatment or to a change of clinical conditions over time. PMID- 7995491 TI - [Adding atropine improves the diagnostic accuracy of dipyridamole-echo test]. AB - BACKGROUND: The clinical experience with dipyridamole stress echocardiography for the diagnosis of coronary artery disease (CAD) revealed that patients with less severe extent of CAD and limited impairment of coronary reserve are frequently not recognized by the test. Increasing myocardial oxygen consumption adding atropine to dipyridamole may improve the diagnostic accuracy of dipyridamole for the detection of CAD. METHODS: Fifty-two patients (48 men, aged 53 +/- 7 years) underwent a high-dose dipyridamole-echo stress test (0.84 mg/kg over 10 minutes) and coronary arteriography within 15 days from the test. Eighteen out of 52 patients were referred for chest pain; 11 suffered from a previous myocardial infarction (MI) and 23 were studied in the early phase after a first acute MI. Starting after 4 minutes from the end of dipyridamole infusion, atropine was added, in 2 doses of 0.5 mg each, at 1-minute interval in those patients with no echocardiographic evidence of myocardial ischemia after dipyridamole alone. Left ventricular wall motion was analyzed on a 11-segment left ventricular model in a qualitative manner. RESULTS: Dipyridamole-echo stress test was positive in 23/52 (44%) and negative in 29/52 (56%) patients. In these patients atropine was added resulting in an additional echo positivity in 14/29 patients. Coronary arteriography was normal in 6 patients (12%); 1-vessel CAD was diagnosed in 23 (44%), 2-vessel CAD in 13 (25%) and 3-vessel CAD in 10 (19%) cases. The sensitivity for CAD diagnosis was 48% (22/46) for dipyridamole alone and 76% (35/46) for dipyridamole-atropine echo (p < .005), while the specificity was 83% (5/6) and 80% (4/5) respectively. Diagnostic accuracy increased from 52% (27/52) to 75% (39/52) (p < .001). The better diagnostic accuracy of dipyridamole atropine echo stress test was mainly related to the increased sensitivity of the combined test in patients with 1-vessel CAD (from 39% to 70%) (p < .005). Peak heart rate was significantly higher after the addition of atropine (100 +/- 17 beats/min) compared to basal (64 +/- 10) and dipyridamole (85 +/- 12) in those patients with a positive dipyridamole-atropine echo stress test. No limiting side effects were elicited with the addition of atropine to dipyridamole. CONCLUSIONS: The combination of atropine and dipyridamole induces a chronotropic stress adjunctive to flow maldistribution phenomena that permits to increase diagnostic accuracy of dipyridamole-echo stress test particularly in patients with less severe extent of CAD; it is usually well tolerated and safe and may be considered as a useful procedure for optimizing diagnostic value of dipyridamole-echo stress test. PMID- 7995493 TI - [Manual obliteration of femoral artery pseudoaneurysm. Report of a case and brief review of the literature]. AB - The authors report a case of non-surgical repair of a femoral artery pseudoaneurysm due to percutaneous catheterization. The procedure was performed by direct manual compression under intermittent color-flow duplex ultrasound control. Some conditions reported in the Literature as unfavorable for a prompt resolution were present (long time interval between invasive procedure and treatment, anticoagulant medication); nevertheless the manoeuvre was successful after only 20'. In comparison with previous experiences (reporting direct compression with the ultrasound transducer or with a mechanical vascular clamp device) the authors underline some observations: a) direct manual compression seems to guarantee a better stability in the optimal position allowing flow interruption in the lesion; b) ultrasound guide is necessary to prove the efficacy of compression, but a continuous monitoring doesn't seem necessary; c) in order to stop the procedure perhaps it is sufficient to interrupt completely the flow in the pseudoaneurysm cavity; a small flow, limited to the neck of the lesion, can be resolved if a pressure bandage is applied and the patient is maintained at bed rest for 12 hours. Manual, ultrasound guided obliteration may be considered a safe and efficacious method for non-surgical treatment of femoral artery pseudoaneurysms. PMID- 7995492 TI - [Exercise 201-thallium myocardial scintigraphy in left bundle branch block]. AB - BACKGROUND: Reduced septal uptake of 201-Thallium in patients with left bundle branch block is reported in literature as having a variable frequency (between 14% and 100%) and in such patients the value of exercise Thallium-scintigraphy for the diagnosis of the left anterior descending coronary artery disease is limited by the great number of false-positive tests. The aim of this study was to assess the prevalence and the diagnostic sensitivity of this septal defect in a group of patients with left bundle branch block. METHODS: We evaluated the exercise 201-Thallium myocardial scintigraphy of 54 patients with a stable left bundle branch block. The clinical and/or echocardiographic evaluation excluded the presence of primitive, valvular and hypertensive cardiomyopathies and of previous myocardial infarction. The planar myocardial scintigraphic imaging was acquired according to the "stress-redistribution" protocol. Only 37 patients underwent an echocardiographic examination and following clinical and/or scintigraphic indications; 27 patients underwent a coronary angiography for the evaluation of coronary stenosis. RESULTS: The 201-Thallium imaging showed septal defects in 36 patients (67%) and the presence of defects in other segments in 14 patients. The echocardiographic evaluation showed an interventricular septal defect contraction abnormality in 19 cases in the 27 patients with septal defect and in 4 cases in the 10 patients with negative scintigraphy (Fisher NS). Twenty seven patients (23 with- and 4 without septal defect) underwent a coronary angiography, which showed in 6 cases critical stenosis of the left descending anterior artery, in 5 of the right coronary, in 3 of the Circumflex artery and in 16 normal coronary angiograms. The presence of the septal uptake defect showed a diagnostic sensitivity and specificity for the detection of the left anterior descending coronary artery disease of respectively 67% and 52% (whereas using a semi-quantitative analysis of 100% and 19%). The scintigraphy showed a sensitivity and specificity for the detection of the right coronary artery disease of respectively 80% and 100% and for the circumflex coronary artery stenosis of 0% and 100%. CONCLUSIONS: We found a high prevalence of septal perfusion defects (67%) and this results shows a high sensitivity but a low specificity for the diagnosis of the left anterior descending coronary disease; the semi-quantitative analysis improves the sensitivity, but leads to a further reduction of the specificity. The female patients had a prevalence (70%) similar to the general population but demonstrated a higher percentage of false-positive. The 201-Thallium scintigraphy has a high diagnostic accuracy for the detection of the right coronary artery stenosis, while it is less accurate regarding the circumflex artery disease. PMID- 7995494 TI - [Agenesis of the left pericardium: report of a case]. AB - We report a case of left pericardial agenesia in a 44 year old woman. Clinical picture was not specific on clinical field: atypical chest pain, asthenia, syncope, cystolic murmur 1/6 Levine on the second left interspace were found. ECG showed clockwise deviation of axis in the precordial leads and incomplete right bundle branch block. Chest X-ray showed marked levocardia and dilatation of pulmonary trunk. Levocardia increased with the patient on the left side. Echocardiography (possible only with patient recumbent on his right side) was normal. Magnetic resonance imaging showed absence of the left pericardium. We analyse the diagnostic problems and the prognostic doubts of this rare congenital anomaly. PMID- 7995495 TI - [Genetic basis of arterial hypertension: new findings in molecular research methods]. AB - Arterial hypertension is thought to derive from an interaction between genetic and environmental factors. Primary hypertension is currently deemed to be under complete polygenic control but highly heterogeneous both from the genetic and the pathophysiologic standpoint. In the last few years a widespread application of molecular medicine techniques to epidemiological genetic studies has led to unprecedented progress in unravelling the genetical basis of human hypertension. The current research strategies along with the most recent results in this field are reviewed. PMID- 7995497 TI - [Myocardial scintigraphy and vital myocardium: which tracer should be used?]. PMID- 7995496 TI - [Left ventricular diastolic function in childhood: normal values. Study Group of the S.I.C.P. on the "Non-invasive assessment of ventricular function in childhood"]. PMID- 7995498 TI - [Heart transplantation and its cartesian reasons]. PMID- 7995499 TI - [Systemic thrombolysis contraindicated or ineffective in acute myocardial infarction: conventional therapy or mechanical revascularization or emergency surgery?]. PMID- 7995500 TI - Area variation in psychiatric services: old news or just the beginning? PMID- 7995501 TI - A small area analysis of psychiatric hospitalizations to general hospitals. Effects of community mental health centers. AB - Population-based psychiatric admission rates vary across geographic areas, but reasons for this variation are unknown. Insofar as Community Mental Health Centers (CMHCs) provide outpatient services that may deter the need for hospitalization, the presence and structural characteristics of CMHCs may have an impact on a population's psychiatric admission rates. This study uses small area analysis to examine how general hospital psychiatric admission rates are associated with CMHC characteristics. Based on a survey of all CMHCs in Iowa and corresponding small area variation data, it was found that population admission rates were higher in areas closer to the CMHC and lower in outlying catchment areas, adjusting for age, sex, and urban/rural differences in populations. There was little evidence that differences in staffing and service variables influenced admission rates, although greater CMHC staff coverage by social workers and psychiatric residents was associated with lower admission rates. The results suggest that CMHCs do not lower an area's hospitalization rate, and in fact, the presence of CMHCs may promote a "supplier-induced demand" phenomenon of higher admissions. PMID- 7995502 TI - A psychodynamic view of the chronic fatigue syndrome. The role of object relations in etiology and treatment. AB - The chronic fatigue syndrome (CFS) is a constellation of physical and psychological symptoms including incapacitating fatigue associated with a marked reduction in activity. Although the etiology of CFS is unclear, reports in the literature suggest the presence of both physical and psychological dysfunction in this patient population. These findings have led to a debate between those who consider CFS to be primarily organic in origin and those who view CFS as a primary psychiatric disorder characterized by somatic preoccupations. This debate led the authors to develop a working model for CFS designed to integrate the psychological and physiological findings, based on the hypothesis that early object relations have an etiologic relationship to CFS. This hypothesis then formed the rationale for a psychoanalytic treatment approach which will be described. There are no published case reports describing psychoanalytic psychotherapy as a primary treatment modality for this patient population. The current paper attempts to fill a void. Two case reports of long-term (> 18 months), intensive (2-3 times per week) psychoanalytic psychotherapy with CFS patients referred by infectious disease specialists at a university teaching hospital will be presented. The following aspects of the treatment will be highlighted: 1) the unique opportunity afforded by this treatment to view the nature of CFS, namely, the intimate relationship over time of fatigue symptoms to disturbances in object relationships, particularly within the transference; (2) the improvement in symptoms when this relationship is seen and understood by the patient; (3) the importance of the patient-therapist bond as a facilitating medium for clinical improvement; (4) the challenges involved in treating CFS patients with psychotherapy. PMID- 7995503 TI - Evaluating consultation psychiatry residents. AB - The overall goal of this report is to provide a list of recommendations to consultation-liaison (C-L) unit chiefs for the evaluation of psychiatric residents in conjunction with the latters' assignments to the C-L service. Following a fairly extensive review of references on evaluation, the authors developed 13 recommendations: written examination materials; development of problem-solving assessment techniques; Case Presentation Inventory; and peer assessment and other nontraditional sources of performance ratings. The authors emphasize the need for direct observation of resident performance, and the problem of achieving good interrater reliability when using subjective ratings of resident performance. PMID- 7995504 TI - Patient allegations of sexual abuse against psychiatric hospital staff. AB - In order to determine prevalence and characteristics of patient allegations of sexual abuse against psychiatric hospital staff and to illustrate the impact of allegations on a unit, we surveyed 255 directors of psychiatric units. We requested detailed descriptions of one or two incidents and report a clinical vignette. Thirty-six percent of the programs reported patient allegations of sexual abuse by a staff member during 1985-1991. Allegations represented a wide range of unit types and patient characteristics. We conclude that patient allegations of staff sexual abuse, which have powerful effects on those involved, are not isolated, rare events. Procedural recommendations to address allegations are made. PMID- 7995505 TI - Progressive muscle relaxation and guided imagery in cancer patients. AB - The aim of this study was to gather information on the immediate and long-term effects of six sessions of group Progressive Muscle Relaxation with Guided Imagery on the psychological distress of self-referred cancer patients. Patients' psychological distress and coping with cancer were assessed by three self reports: the Multiple Locus of Control, the Impact of Events Scale (IES), and the Brief Symptom Inventory (BSI). Of the 123 patients who started group therapy, 37 dropped out during its course. The 86 patients who completed the intervention showed marked improvement on both BSI and IES, an improvement maintained over the next 6 months in 58 patients who continued assessment through the followup period. PMID- 7995506 TI - Electroconvulsive therapy during high-risk pregnancy. AB - Pregnancy increases the risk of injury associated with mental illness. The varieties of malnutrition, substance abuse, and aggression that may accompany mental illness can injure the unborn child in more severe ways than the patient herself. Dangers associated with illness-related behavior can outweight the risks of pharmacotherapy, but no psychotropic drug is approved for use during pregnancy. Failure to produce a prompt or lasting remission of psychiatric symptoms also is a significant possibility with medication. The morbidity from continued illness and the incompletely described adverse effects of psychotropic drugs increases the attractiveness of ECT for severely depressed pregnant patients, especially with associated high-risk conditions. This paper discusses physiologic changes occurring during pregnancy and ECT and reviews contemporary monitors of maternal and fetal well-being. Guidelines are suggested for ECT during regular and high-risk pregnancies. The authors conclude that using additional precautions with high-risk pregnant patients permits ECT to be given with relative safety; medical and obstetric risk factors need not prevent its use. PMID- 7995507 TI - Use of psychiatric services by patients referred to a consultation unit. AB - The psychiatric case registers for the hospital catchment area were examined to determine the use of psychiatric services over a 14-year period by a 4-year cohort of consecutive inpatient referrals to the consultation-liaison service of a British general hospital. Two-thirds of the subjects had no other psychiatric care during the survey period, but a third made considerable use of a wide range of specialist psychiatric services. Alcohol problems and dementia were notably associated with complex history of psychiatric management. Management of patients with repeated episodes of psychiatric care requires close collaboration with other services. PMID- 7995508 TI - Phenylpropanolamine-induced psychosis. Potential predisposing factors. AB - Phenylpropanolamine (PPA) is a sympathomimetic drug contained in numerous over the-counter and prescription decongestants and appetite suppressants. A range of adverse effects have been reported, including neuropsychiatric reactions in patients known to be taking recommended doses. Given that psychiatric symptoms are not included in the manufacturer's lists of adverse drug reactions, the incidence may be significantly higher. We report a cae of paranoid psychosis following use of a decongestant containing PPA and summarize the case report literature of psychiatric adverse effects to PPA in which doses were known and stated to be within recommended guidelines. A pattern of possible risk factors emerges from these reports. These may include 1) symptoms or history of mood spectrum disorder, 2) history of psychosis, 3) female sex, 4) family history of psychiatric disorder. The possibility that a higher incidence of adverse events occurs in a vulnerable population has not been systematically addressed, and seems called for. We recommend that physicians specifically inquire about patients' use of decongestants and diet aids. In half of the above cases, symptoms resolved without the use of antipsychotics. PMID- 7995510 TI - Affective psychosis in Eales' disease and response to sodium valproate. PMID- 7995509 TI - Use of methylphenidate in a case of mild, inoperative, idiopathic, normal pressure hydrocephalus. PMID- 7995511 TI - [Ambiguity of translation: a eukaryotic version?]. AB - In this review, the results of studies on genetic control of translation in the yeasts are considered and analyzed. The studies were performed on the system of the SUP35(SUP2) and SUP45(SUP1) genes. Based on data from genetic analysis, the study of protein synthesis in mutants at these genes, sequencing of both genes, deletion analysis of their functions, and the discovery of homologues of these genes in other eukaryotes, it may be assumed that the gene system under study is a specific evolutionarily conservative system for eukaryotes. This system not only controls translational fidelity, but also ensures integration of translation with other cellular processes. PMID- 7995513 TI - [Directed character of genetic variation during long-term selection of Drosophila melanogaster strains for adaptively important characters]. AB - Related fly strains that were selected for differences in reproductive function for about 700 generations were studied. The low-active (LA) strain differs from other related and highly active strains of interest at a set of characters. Qualitative differences in the spectrum of viability mutations are retained in strains selected in opposite directions. Low-active strains carry a great number of deleterious mutations. Such mutations are rare in the related highly active strains. Moreover, about 50% of chromosomes in the highly active strains carry supervital mutations, which increase viability. Recombination analysis showed the presence of at least several viability mutations in each chromosome of the strains studied. Unlike highly active strains, the low-active ones are characterized by an extremely high spontaneous mutation rate. The conservation of genetic heterogeneity observed in long-term selected strains, as well as the high mutation rate, must be connected with regular changes in the spectrum of retrotransposons (MDG1, MDG3) and hobo elements characteristic of the strains studied. A special crossing system that induces a sharp increase in LA induction potential in the H-E system of hybrid dysgenesis was developed. PMID- 7995512 TI - [Genetic control of yeast cell morphology]. AB - Yeast cell phenotype and morphology result from the interaction of two processes, polarized growth, on the one hand, and cytokinesis with subsequent division of the cell wall, on the other. Imbalance of the equilibrium of these two principal processes may lead to the occurrence of yeast morphological mutants that generate rough colonies. Two types of such mutants exist, Rgh and Rpm. The Rgh mutants have ellipsoid cells and either form chains or generate clumps at high frequency. These changes in heterothallic strains of saccharomyces occur due to recessive mutations in any of 11 non-linked genes. In homothallic strains of saccharomyces, the trait Rgh depends on the complementary interaction of one dominant and two recessive genes. Rpm mutants generate rough colonies, which contain elongated cells that give rise to pseudomycelium. The mutants obtained are recessive and occur in six non-linked genes. The Rpm mutants represent an example of the manifestation of mycelium-yeast dimorphism in fungi, and this case may be regarded as a simple morphogenetic model. PMID- 7995514 TI - [Mechanisms ensuring the resistance of the genetic material of the cell to stress exposures]. AB - A brief review of studies performed in the Department of Genetics of St. Petersburg University by M.E. Lobashev and his disciples is presented. The results of these studies prove that the formation of a mutation is a multistage process involving many cell and organism systems (including repair systems, systems that determine sexual dimorphism, etc.), which are affected by environmental factors (e.g., extreme temperatures). They can hinder or accelerate the mutational process, in this way providing both a superadditive effect and adaptive response. Recent studies deal with a universal system of heat shock proteins, which is involved in the maintenance of resistance of genetic material and genetic processes in the cell. PMID- 7995515 TI - [Pheromonal regulation of genetic processes: research on the house mouse (Mus musculus L.)]. AB - A study of the influence of pheromone stressor(s) on proliferating germ and somatic cells was performed on laboratory lines of house mouse in the context of the physiological hypothesis of mutation process, proposed by M.E. Lobashev in 1947. Data from experiments are presented, and results obtained during last 10-15 years are discussed. The adaptive role of cytogenetic and other observed pheromonal effects is considered. The possible existence of interorganism systems of genetic regulation is discussed, the search for and study of which may help in more complete understanding of the regularities of functioning of genetic material. PMID- 7995516 TI - [The special genetics of the chicken]. AB - Studies on inheritance of a number of traits, peculiarities of the karyotype, and chromosome mapping in chicken are reviewed. Prominent among these are studies on behavioral genetics, which are performed at different levels and in different aspects: neuromuscular apparatus and entire organism, behavior and population structure, and behavior and individual fecundity. Creation of lines that differed in neural reactivity provided a model for study of systemic control of cytogenetic processes. On the basis of data on genetic control of feather color, a hypothesis was proposed concerning the mechanism of action of the eumelanin suppressor gene. In the Department of Genetics and Breeding of St. Petersburg State University, research was reformed on the relationships between hereditary and non-hereditary variability, as well as the determination and realization of the genotype reaction norm. In the framework of this research, a study on the variability of chicken growth was performed. A single short-term cooling of chickens during the first week of life resulted in a prolonged (up to eight-week) alteration of growth rate. The following structural genes were mapped in chicken mitotic chromosomes by the method of in situ hybridization: the gene for the transferrin receptor, the beta-globin gene cluster, the homologues of the human ZFY and SRY gene families, the viral oncogene v-fos, and a TG-rich minisatellite. PMID- 7995517 TI - [The Petergof genetic collection of microorganisms]. AB - The Petergof Genetic Collection (PGC) of microalgae was created in the 1960s during study of the regularities of mutational processes. A collection of yeasts has been maintained at the Department of Genetics and Selection of St. Petersburg State University since 1977. This collection contains some 1000 genetically marked strains of the yeasts Saccharomyces cerevisiae and Pichia methanolica, and the algae collection comprises about 600 strains of Chlamydomonas reinhardtii, Chlorella vulgaris, and Scenedesmus obliquus. The structure of the collection and the employment of strains in basic and applied research, as well as for educational purposes, are discussed. On the basis of the original software GENESTRAIN, a yeast PGC database (DB) was developed. A visual interface that contains information about selection of Ch. reinhardtii strains and crosses made was created in the HyperCard operational system. PMID- 7995518 TI - Intercellular C-signaling and the traveling waves of Myxococcus. AB - Early in their development into fruiting bodies, Myxococcus xanthus cells organize themselves into dense bands that move as trains of traveling waves. C factor, a 20-kD cell-surface bound protein, is a short-range developmental signal molecule required for these waves. What is the role of C-factor in the wave pattern? It is proposed that oriented collisions between cells initiate C signaling, which, in turn, causes individual cells to reverse their direction of gliding. Cells would move about one wavelength and then reverse. Several lines of experimental evidence support these proposals: (1) Cells that suffered a mutation in the signal transduction pathway that controls the spontaneous reversal frequency lost the ability to form waves; (2) presentation of developing cells with detergent-solubilized C-factor increased the mean frequency of single cell reversal by three-fold; and (3) fluorescently labeled cells in the waves were tracked, and it was found that they moved and reversed on linear paths along the axis of wave propagation. Similar numbers of cells were found moving in the direction of ripple propagation, and in the reverse direction, as expected. (4) Dilution of C-signaling-competent cells with C-factor-deficient cells increased the wavelength as the probability of productive collision decreased. The waves exemplify a way that a multicellular pattern of stripes can be produced de novo, one that maintains a uniform 50-microns separation between stripes over a distance as large as 1 cm. PMID- 7995519 TI - cAMP regulates morphogenesis in the fungal pathogen Ustilago maydis. AB - The fungal pathogen Ustilago maydis exhibits a dimorphic switch from budding to filamentous growth in response to mating interactions and environmental conditions. We have found that disruption of the uac1 gene, encoding adenylate cyclase, results in a constitutively filamentous phenotype. Budding is restored to the uac1 mutant upon growth in the presence of cAMP or by extragenic suppression because of a mutation in the ubc1 gene. The ubc1 gene encodes a type II regulatory subunit of cAMP-dependent protein kinase (PKA); defects in this gene attenuate the filamentous growth that normally occurs in response to mating and exposure to air. Growth of wild-type cells in cAMP and mutation of the ubc1 gene also cause defects in the separation of mother and daughter cells (cytokinesis) and alter bud site selection. These results indicate a key role for cAMP and PKA in morphogenesis in U. maydis; this role may be common among dimorphic fungal pathogens. PMID- 7995520 TI - Myc-mediated apoptosis requires wild-type p53 in a manner independent of cell cycle arrest and the ability of p53 to induce p21waf1/cip1. AB - Deregulated expression of the c-myc proto-oncogene can lead to apoptosis under certain physiological conditions. By introducing a conditionally active Myc allele into primary embryo fibroblasts null for p53, and into fibroblasts without endogenous p53 expression but ectopically expressing a temperature-sensitive p53 allele, we show that expression of wild-type p53 is required for susceptibility to Myc-mediated apoptosis. Although ectopic expression of wild-type p53 blocked cells in the G1 phase of the cell cycle, G1 arrest by isoleucine starvation, in a manner independent of p53, did not confer susceptibility to apoptosis. Thus, growth arrest per se is not sufficient to induce Myc-mediated apoptosis; instead, a property intrinsic to p53 is specifically required. Moreover, apoptosis did not require induction of p53 target proteins, including the cyclin-dependent kinase inhibitor p21waf1/cip1. Therefore, the role of p53 in apoptosis may be distinct from its role in cell cycle arrest. PMID- 7995521 TI - Lymphohematopoietic progenitors immortalized by a retroviral vector harboring a dominant-negative retinoic acid receptor can recapitulate lymphoid, myeloid, and erythroid development. AB - The lymphohematopoietic progenitors represent < 0.01% of nucleated marrow cells. Here, we describe the immortalization of the murine lymphohematopoietic progenitors by a retroviral vector harboring a dominant-negative retinoic acid receptor. The immortalized progenitors proliferate as a stem-cell-factor dependent clonal line EML that spontaneously generates pre-pro-B lymphocytes and erythroid and myeloid progenitors. Upon stimulation with interleukin-7 and stromal cells, the pre-pro-B lymphocytes express RAG-1 and undergo D-J rearrangements of the immunoglobulin heavy-chain genes. With erythropoietin the erythroid progenitors proliferate and differentiate into red cells. Generation of the common progenitors for neutrophils and macrophages is suppressed in EML but is inducible by high concentrations of retinoic acid. An additional block in neutrophil differentiation occurs at the promyelocyte stage but can also be overcome by high concentrations of retinoic acid. These studies demonstrate a reproducible way to immortalize lymphohematopoietic progenitors and implicate specific roles for retinoic acid receptors at two distinct stages of hematopoiesis. PMID- 7995522 TI - Influence of a steroid receptor DNA-binding domain on transcriptional regulatory functions. AB - We have isolated two independent mutations in the DNA-binding domain of the rat glucocorticoid receptor, P493R and S459A, that implicate DNA binding in the control of attached transcriptional activation domains, either that of the receptor itself or of VP16. The mutants are capable of activating transcription normally, but unlike wild-type receptors, they interfere with particular transcriptional activators in yeast and mammalian cells, and inhibit growth when overexpressed in yeast. The mutant residues reside at positions within the three dimensional structure of the receptor that could, in principle, transduce structural changes from the DNA-binding surface of the receptor to other functional domains. These findings, together with the salt dependence of specific and nonspecific DNA binding by these receptors, suggest that specific DNA acts as an allosteric effector that directs the functional interaction of the receptor with targets of transcriptional activation and that the P493R and S459A mutants mimic the allosteric effect of specific DNA, allowing the receptor to interact with regulatory targets even in the absence of specific DNA binding. PMID- 7995523 TI - The WD repeats of Tup1 interact with the homeo domain protein alpha 2. AB - Tup1 and Ssn6 transcriptionally repress a wide variety of genes in yeast but do not appear to bind DNA. We provide genetic and biochemical evidence that the DNA binding protein alpha 2, a regulator of cell-type-specific genes, recruits the Tup1/Ssn6 repressor by directly interacting with Tup1. This interaction is mediated by a region of Tup1 containing seven copies of the WD repeat, a 40 amino acid motif of unknown function found in many other proteins. We have found that a single WD repeat will interact with alpha 2, indicating that the WD repeat is a protein-protein interaction domain. Furthermore, a fragment of Tup1 containing primarily WD repeats provides at least partial repression in the absence of Ssn6, suggesting that the repeats also mediate interaction between Tup1 and other components of the repression machinery. PMID- 7995524 TI - TFIIF-TAF-RNA polymerase II connection. AB - RNA polymerase transcription factor IIF (TFIIF) is required for initiation at most, if not all, polymerase II promoters. We report here the cloning and sequencing of genes for a yeast protein that is the homolog of mammalian TFIIF. This yeast protein, previously designated factor g, contains two subunits, Tfg1 and Tfg2, both of which are required for transcription, essential for yeast cell viability, and whose sequences exhibit significant similarity to those of the mammalian factor. The yeast protein also contains a third subunit, Tfg3, which is less tightly associated and at most stimulatory to transcription, dispensable for cell viability, and has no known counterpart in mammalian TFIIF. Remarkably, the TFG3 gene encodes yeast TAF30, and furthermore, is identical to ANC1, a gene implicated in actin cytoskeletal function in vivo (Welch and Drubin 1994). Tfg3 is also a component of the recently described mediator complex (Kim et al. 1994), whose interaction with the carboxy-terminal repeat domain of RNA polymerase II enables transcriptional activation. Deletion of TFG3 results in diminished transcription in vivo. PMID- 7995525 TI - Conserved functional domains of the RNA polymerase III general transcription factor BRF. AB - In Saccharomyces cerevisiae, two components of the RNA polymerase III (Pol III) general transcription factor TFIIIB are the TATA-binding protein (TBP) and the B related factor (BRF), so called because its amino-terminal half is homologous to the Pol II transcription factor IIB (TFIIB). We have cloned BRF genes from the yeasts Kluyveromyces lactis and Candida albicans. Despite the large evolutionary distance between these species and S. cerevisiae, the BRF proteins are conserved highly. Although the homology is most pronounced in the amino-terminal half, conserved regions also exist in the carboxy-terminal half that is unique to BRF. By assaying for interactions between BRF and other Pol III transcription factors, we show that it is able to bind to the 135-kD subunit of TFIIIC and also to TBP. Surprisingly, in addition to binding the TFIIB-homologous amino-terminal portion of BRF, TBP also interacts strongly with the carboxy-terminal half. Deleting two conserved regions in the BRF carboxy-terminal region abrogates this interaction. Furthermore, TBP mutations that selectively inhibit Pol III transcription in vivo impair interactions between TBP and the BRF carboxy-terminal domain. Finally, we demonstrate that BRF but not TFIIB binds the Pol III subunit C34 and we define a region of C34 necessary for this interaction. These observations provide insights into the roles performed by BRF in Pol III transcription complex assembly. PMID- 7995527 TI - Regulation of rDNA transcription in chloroplasts: promoter exclusion by constitutive repression. AB - Spinach chloroplasts contain two types of RNA polymerases. One is multimeric and Escherichia coli-like. The other one is not E. coli-like and might represent a monomeric enzyme of 110 kD. The quantitative relation of the two polymerases changes during plant development. This raises the question, how are plastid genes transcribed that contain E. coli-like and non-E. coli-like promoter elements during developmental phases when both enzymes are present? Transcription of the spinach plastid rrn operon promoter is initiated at three sites: P1, PC, and P2. P1 and P2 are preceded by E. coli-like promoter elements that are recognized by E. coli RNA polymerase in vitro. However, in vivo, transcription starts exclusively at PC. We analyzed different promoter constructions using in vitro transcription and gel mobility-shift studies to understand why P1 and P2 are not used in vivo. Our results suggest that the sequence-specific DNA-binding factor CDF2 functions as a repressor for transcription initiation of the E. coli-like enzyme at P1 and P2. We propose a mechanism of constitutive repression to keep the rrn operon in all developmental phases under the transcriptional control of the non-E. coli-like RNA polymerase. PMID- 7995526 TI - A possible role for the 60-kD Ro autoantigen in a discard pathway for defective 5S rRNA precursors. AB - The Ro autoantigen is a 60-kD protein that is usually found in small cytoplasmic RNA-protein complexes known as Ro RNPs. Although the Ro RNPs are abundant and conserved components of a variety of vertebrate and invertebrate cells, their function is unknown. We have discovered that the Ro protein is also found complexed with certain variant 5S rRNAs in Xenopus oocytes. These RNAs contain one or more point mutations compared with the major oocyte 5S rRNA sequence as well as additional nucleotides at the 3' end. We demonstrate that the Ro protein binds specifically mutant 5S rRNAs containing 3' terminal extensions. These mutant RNAs are processed inefficiently to mature 5S rRNA and most eventually are degraded. The observation that the Ro autoantigen specifically associates with defective 5S rRNA precursors suggests that this protein may function as part of a novel quality control or discard pathway for 5S rRNA production. PMID- 7995528 TI - Treatment of periorbital rhytids. PMID- 7995529 TI - Lower eyelid blepharoplasty and other aesthetic considerations. PMID- 7995530 TI - Botulinum toxin A: a novel method to remove periorbital wrinkles. PMID- 7995531 TI - Muscle suspension blepharoplasty. PMID- 7995532 TI - Surgical therapy of the paralyzed eyelid. PMID- 7995533 TI - Evaluation and management of eyelid trauma. PMID- 7995534 TI - Combined approach to eyelid surgery in Graves' disease. PMID- 7995535 TI - Combined approach of ptosis and blepharoplasty surgery. PMID- 7995536 TI - Diagnosis and management of acquired blepharoptosis and dermatochalasis. PMID- 7995537 TI - Techniques in periocular reconstruction. PMID- 7995538 TI - Complications of blepharoplasty surgery. PMID- 7995539 TI - [Radioprogestins. Their clinical use]. AB - It was obtained by synthesis a radioprogestin-iodine-131 and proved in two patients with hormono-dependent meningioma to progesterone with very good results in the scan of cerebral tumours localization; and in one patient in the treatment of this kind of tumour. No radiotoxicity or intolerance was present until today in six month of follow-up of this preliminary uses of radioprogestin in cerebral tumours hormono-dependent to progesterone; so it is proposed the use of this new radiopharmaco for the diagnosis and treatment of this tumours. PMID- 7995540 TI - [Stress urinary incontinence. A comparison of of 4 methods of cystourethropexy. A 2-year follow-up]. AB - All successful operations for relief of genuine stress urinary incontinence (SUI) have three objectives: elevation and retropubic maintenance during stress of the urethrovesical junction. The present study was realized at the Urogynecologic Service of the "Luis Castelazo Ayala" hospital IMSS to evaluate the results in a two years follow up of 597 patients that suffered from SUI treated by retropubic urethropexy, from February 1984 to May 1991. Patients were studied according to the service norms, previously published. We realized four types of procedures: Pereyra (379 cases), Burch (90 cases), Marchall-Marchetti-Kratz (60 cases) and Powell surgery (68 cases). Vaginal approach was realized in cases of pelvigenital statics disturbances like cysto- or rectocele; and abdominal approach was indicated in patients with enlarged uterus or pelvic masses. The complications rate was 15.3%. Success rate was 87.06% for all procedures and not statistic significance was found (p > or = 0.1 and X2 = 6.15), the best rate to the Burch and Pereyra procedures. We conclude the most important tip to successful rate in SUI surgery is correct choice of the procedure according to the patient. PMID- 7995541 TI - [The ovarian hyperstimulation syndrome. Institutional experience]. AB - Thirty patients with OHS were analyzed; all of them had to be hospitalized. There was no difference as to sterility time and syndrome appearance. The use of menotropines caused more frequently the syndrome. There was multiple pregnancy in 33%. Abortion incidence was 16%. As the etiology is unknown there is not an adequate treatment, and care is for maintenance. Prevention is the best option. PMID- 7995542 TI - [Abdominal hysterectomy at the Hospital de Especialidades Dr. Miguel Dorantes Mesa, S.S. A report on 140 cases]. AB - Results from a study involving 140 hysterectomies performed at the "Miguel Dorantes Mesa" Hospital S.S. of Xalapa, Veracruz, between 1990 and 1992, are presented. The variables considered in the study were age, gyneco-obstetric history, pre-operatory indication, associated surgery, anatomopathology diagnosis and its correlation with the pre-operatory diagnosis, operatory technique, associated surgery, size of the uterus, type of endometrium of the quirurgic piece and complications in the immediate and late transoperatory. The results obtained here were also compared with some available from similar studies. The results showed that the main indication was due to pre-malign lesions, followed by benign neoplasias and only 4% due malign processes. The most frequent type of surgery was found to be the extrafascial hysterectomy with the salpingo oophorectomy as associated surgery. The confirmation of the diagnosis by the anatomopathologic study was 76.1%. The most common type of complications encountered were two bladder lesions, and one of ureter; which were repaired during the transoperatory; two vesicovaginal and one ureterovaginal fistula. There was no mortality. PMID- 7995543 TI - [Pregnancy after a partial dearterialization of the uterus. A case report]. AB - A case of a 27-year-old woman with a previous partial uterine dearterialization for uterine atony in its first gestation, is presented. This woman asked advise for secondary infertility and after a laparoscopic adhesiolysis she achieved pregnancy. With the exception of tubo-peritoneal factor all other infertility studied factors were normal. Partial uterine dearterialization must be taken in account in patients with obstetric bleeding and posterior fertility expectatives. PMID- 7995544 TI - [Syringomyelia and pregnancy. A case report]. AB - This report refers to the case of a 39-year-old woman, fourth gestation, who during her first pregnancy developed neurologic deficit of the left hand, which slowly progressed getting to affect during seven years, all the left upper extremity and the right hand. During this time, she had two abortions, and between the third and fourth pregnancies, because of the clinical suspicion, laboratory tests were done, finding by electromyography, lesion of anterior process of spinal chord at cervical level. During this fourth pregnancy, neurologic deficit increased and it was decided to interrupt pregnancy by cesarean section under epidural block at 38 weeks of gestation. According to our knowledge this syringomyelia case and pregnancy, is the first one reported in our country. PMID- 7995545 TI - [Cesarean section. Hysterorrhaphy in one plane]. AB - Morbimortality between hysterorraphy in one and two planes, was compared. One hundred patients in whom hysterorraphy in one plane, was done with a control group of one hundred with hysterorraphy in two planes, were studied, and evolution was compared. The time of surgery was 50% lees with the hysterorraphy in one plane. (P minor 0.0001). Bleeding of 100 cc. lees (P minor 0.001). There was no difference about complications of both methods. There was no difference in morbimortality. The cicatrization during sixty days after surgery is the same. PMID- 7995546 TI - [The neuroendocrinological and histopathological assessment of normogonadotropic azoospermic patients: the usefulness of the GnRH stimulation test]. AB - This study evaluates the effect of gonadotropin releasing hormone (GnRH) administration on serum levels of FSH and LH. Also, relate those results with histopathologic findings of testicular biopsies. This was a prospective, clinical trial with a control group. It was done at Department of Reproductive Biology "20 de Noviembre" Hospital, ISSSTE, Mexico City. Fifteen azoospermic, normogonadotropic patients without testicular atrophy and ten normal men use as control group. A GnRH challenge test was made in both groups, two days after we perform a testicular biopsy in patients with azoospermia. There was no significant difference in serum LH concentrations between the two groups, neither before or after GnRH challenge test. There was a statistical difference between serum FSH values of azoospermic patients, than those of control group, the former with higher values than those of the latter. As worst testicular damage was, we found also a higher FSH value on the GnRH challenge test. The GnRH challenge test perform in azoospermic, normogonadotropic patients is very helpful to detect those patients with gonadal damage. As higher the FSH values were, we found that an abnormal testicular biopsy was also more common. PMID- 7995547 TI - [Care of the delivery following a cesarean section]. AB - A retrospective study to determine the risks of normal delivery after cesarean section, was done. The inclusion criteria were found in 116 patients in six years covering the study. All the patients were permitted normal delivery and none received ocitocin. Sixty six patients accomplished delivery, which corresponds to 57%. In the rest of patients cesarean section was performed. The probability of ending in delivery was associated to women with three or more gestas. But cephalo pelvic disproportion and fetal suffering, were associated to greater probability of ending in cesarean section. There was no dehiscence of uterine scar. It is concluded that with well established requisites it is possible to resolve by delivery with a great degree of confidence, at least 50% of cases with previous section. PMID- 7995548 TI - [Ovarian cancer. An anatomicopathological study]. AB - We studied 118 patients with primary ovarian cancer at the Civil Hospital of Guadalajara over a ten-years period; to evaluate incidence, risk factors, clinical aspects, pathology and treatment. Twenty per cent of the patients were classified as stage I, 14 cases (11.8%) stage II, 37 (31%) were stage III and 43 (36%), stage IV. First-stage disease was confirmed by laparotomy; average age was fifty years old, commonly found in patients with invasive carcinoma. Seventy seven patients received postoperative chemotherapy with cisplatin plus adriamycin and ciclophosphamide or vincrystin, and twelve radiotherapy. Thirteen were evaluated by second look laparotomy, 12 of whom were without clinical residual disease; in 6 we found macroscopic residual tumor. Follow-up was done in 89 patients, and there wasn't clinic disease through 12 to 48 months, with 21 months average. The clinicopathologic study showed predominance of serous and cystic surface epithelium tumours. The aspects of the gross anatomy of the malignant tumours are important from the viewpoint of the benign tumours differentiation. PMID- 7995549 TI - [Genuine stress urinary incontinence. An analysis of 2 surgical technics: Pereyra's and Burch's]. AB - Two hundred and twenty-nine patients operated for genuine stress urinary incontinence by two surgical techniques, were studied. Risk factors were analyzed: age, gesta, para, and added gynecological pathology. They were placed in two groups. Group I formed by operated patients with Pereyra's technique (136), and Group II operated by Burch's technique (93). There were no differences as far as general characteristics of patients in both groups. More frequent added pathologies for Group I were pelvic statics changes, and for Group II, uterine myomatosis. Technically there were no advantages for one technique as compared with the other one, independently of indications for each one. PMID- 7995550 TI - [Septic cervical pregnancy. A case report]. AB - One clinical case of cervical pregnancy studied at the General Hospital of Acapulco, Guerrero, Mexico, is presented clinically it was manifested as septic abortion and diagnosed by ultrasonography. In the past 12 years of establishment, 30,000 deliveries have been recorded and during this period, only four well documented cases were found and two of the previously reported by one us. Only two cervical pregnancy presenting as abortion, a relationship not emphasized in literature, was made in 1975. PMID- 7995551 TI - [Molecular and clinical aspects of androgen insensitivity syndrome]. AB - The syndrome of androgen insensitivity is a genetically determined illness occurring in subjects with a karyotype 46XY and female or male phenotype. The insensitivity to androgens is caused by the mutations in the androgen receptor gene, comprising 8 exons and localized on chromosome X near the centromere, between Xq13 and Xp11. The androgen receptor belongs to a family of steroid hormone receptors which possess common structural features since it comprises six functional regions (domains) of which the DNA binding domain has a characteristic zinc fingers motif. The lack, deficiency or the disturbance in the function of the receptor, results in a set of clinical symptoms which allow to distinguish four distinct clinical forms of the illness: complete and incomplete testicular feminization syndromes, Reifenstein syndrome and the syndrome of male infertility. In this review data from literature were presented and discussed, regarding the structure and action of the androgen receptor in target cells and the significance of the investigations on the structure-function relationship of this receptor in understanding the pathogenesis of the syndrome of androgen insensitivity was emphasized. PMID- 7995552 TI - [Effect of umbilical cord compression on acid-base parameters in blood from the umbilical artery in neonates]. AB - To find out the influence of nuchal cord on neonatal acid-base balance we obtained 117 umbilical artery blood samples from full-term newborns immediately after cord clamping. In 29 cases umbilical cord entanglement was observed while delivery. For each case we matched control case with basic obstetrical factors comparable. In those two groups no significant difference between mean values of acid-base balance parameters was found. PMID- 7995553 TI - [Bile acids from blood serum of women during normal pregnancy]. AB - Bile acid concentrations were measured enzymatically in study of women through normal pregnancy. Mean serum bile acid levels increased significantly, from 5.3 (SD 0.9) mumol/l at 16 weeks to 7.2 (SD 1.0) mumol/l at term. Serum bile acid concentrations were greater of older women, than of younger women. PMID- 7995554 TI - [Hypomodified phenylalanine transfer RNAs (tRNA(Phe)) in uterine myoma tissue of women]. AB - Phenol extracted crude tRNA samples obtained from uterine myoma tissue were additionally purified on DEAE-cellulose column and were finally fractionated on BD-cellulose column. Fractions eluted by ethanol gradient (concentration from 0% to 20%) were hybridized by dot blot technique with DNA probe which consisted of 15 nucleotides fragment complementary to 3' end of the tRNA(Phe). Five separate distinct peaks were found. According to genetic code rules restricted to two the number of tRNA(Phe) isoacceptors, it is assumed that three major peaks representing roughly 70% of total tRNA(Phe) pool, probably are hypomodified. PMID- 7995555 TI - [Zinc levels in semen of men from childless marriages]. AB - Zinc concentration in human semen was studied on the material of 106 male patients aged 20-35, from childless marriages. Full microscopic examination was performed including number of spermatozoons, mobility, fluxing time, pH, morphological composition, number of leucocytes. Zinc level was measured using spectrophotometric analysis. Trial of relation estimation between zinc concentration and number of live spermatozoons and pH of the semen was taken out. Any significant differences between zinc concentration in the semen from normospermic and oligospermic males were found. There was proved, that semen pH increase was correlated to zinc concentration decrement in the semen fluid. PMID- 7995556 TI - [Chlamydia trachomatis infections of the cervix and postoperative course]. AB - In the paper authors consider the problem if Chlamydia trachomatis infection of urogenital tract exerts an influence on postoperative course in women who were operated in the gynaecology department. 186 women have been examined in this study. Using the criteria for selective screening for Chlamydia trachomatis infection proposed by Handsfield, 29 women with higher risk for chlamydial infection were seperated. The personal details have been obtained by standardized questionnaire. Using the immunoenzymatic test "Chlamydiazyme" the incidence of Chlamydia trachomatis infection of the cervical canal was studied in 29 women from groups of higher risk for this infection. No Chlamydia trachomatis antigens were found in this group. These results don't answer the question if Chlamydia trachomatis infection of urogenital tract exerts an influence on postoperative course in women who were operated in gynaecology department, because it is to small trial. PMID- 7995557 TI - [Neonatal evaluation of obstetrical criteria of prematurity]. AB - Paediatric maturity was assessed in newborns whose birth weight was above or equal to 2500 g, of 1742 women of single pregnancy who delivered vaginally, and in 81 newborns with birth weight below 2500 g, by means of Ballard method. The range of maturity was 39 +/- 3 points of Ballard/Klimek score. There were only 14 newborns with birth weight below 2500 g born before 37 gestational weeks, which is only 30.4% of all newborns with a score below 33 points. The neonatological assessment of physical and neuro-muscular maturity of the newborns, allows to determine the degree of maturity and simultaneously the obstetrical criteria (newborn weight below 2500 g and 37 weeks of pregnancy), indicate only a lower limit of possible maturity. PMID- 7995558 TI - [Prenatal adoption]. AB - This paper shows the psycho-sociological factors which have a serious negative impact on childless families, while stressing the importance of the family as basic environment for the development, education and socialisation of man. It presents numerous disorders which affect parentless children brought up in educational institutions. The solution advocated in this paper is prenatal adoption, which responds to the anguish of both childless families and the mothers of unwanted children. Prenatal adoption is also a significant area of medical activity involving great responsibility of the doctor as the first contact person, who deals directly with the problems of lone pregnant women and abandoned children. The paper informs of the activities of the Prenatal Adoption Centre in Krakow as well as the idea that led to its formation. PMID- 7995559 TI - [Coexistence of three tumors in a giant tumor of the uterus]. AB - The coexistence of three histologically different tumors (Carcinosarcoma corporis uteri, Leiomyosarcoma, Adenocarcinoma endometrial) in a giant tumor of the uterus in 58-year old patient is presented. Operative treatment relied on total hysterectomy was applied. An unusual and rare coincidence of three tumors push us to present the case and to discuss the coexistence of genital tract tumors and diagnosis and treatment of giant pelvis minor tumors. PMID- 7995561 TI - [Psycho-neuro-physiological assessment of post-traumatic stress disorder using event-related potentials]. AB - To evaluate certain aspects of cognitive processing in posttraumatic stress disorder (PTSD), brain event-related potentials, primarily P300, to traumatic stimuli were recorded. 20 Israeli veterans with PTSD of combat origin and matched controls were studied. In a modification of the oddball paradigm, subjects were asked to react to target pictures of traumatic combat-related subjects while ignoring non-target pictures of irrelevant subjects. PTSD patients reacted with an accentuated P300 and prolonged reaction times to the traumatic pictures. In addition, P300 and reaction times to the target pictures were prolonged in PTSD patients as compared to controls. Event-related potentials (P300) to traumatic stimuli can serve as an objective and accurate brain parameter for characterization and diagnosis of PTSD. In addition, it contributes to understanding the pathogenesis of PTSD as a specific impairment in information processing. PMID- 7995560 TI - [Do on-site coronary angiographic facilities influence management and prognosis of acute myocardial infarction?]. AB - Whether the presence of on-site coronary angiographic facilities (CAF) influences the use of invasive coronary procedures and the outcome of acute myocardial infarction in coronary care units was studied. A prospective survey was conducted early in 1992 when 1014 consecutive patients with acute infarction were admitted. Of them 707 (70%) were admitted to coronary care units of hospitals with, and 307 (30%) without CAF. Thrombolytic therapy was given to 46% in both groups. Those admitted to hospitals with CAF underwent more coronary angiographies (26%) and percutaneous transluminal angiography and/or coronary artery bypass grafting (12%) than those without CAF (10 and 5%, respectively--p < 0.005). In-hospital and 1-year mortality were 11 and 18% respectively in those with CAF, vs 10 and 11%, respectively, in those without CAF. All patients treated with a thrombolytic agent had similar mortality, unrelated to the availability of CAF. The survey showed that the availability of on-site coronary angiography facilities led to greater use of invasive coronary procedures in cases of acute myocardial infarction, but there was no significant difference in mortality. PMID- 7995562 TI - [Malignant lymphomas of the head and neck]. AB - Review of 122 head and neck lymphomas diagnosed between 1976 and 1992 revealed 40 extranodal lymphomas. In 30 of them follow-up was available. We review the demographic, clinical, histological and immunohistochemical features of the 30 extranodal lymphomas according to site of origin. Comparison is made between these extranodal lymphomas and nodal non-Hodgkin's lymphomas and cases of Hodgkin's disease first diagnosed in the head and neck area. PMID- 7995563 TI - [Functions of a geriatric facility]. AB - A geriatric facility in a general hospital is a relatively new service, not clearly defined and varying in character from hospital to hospital. A geriatric rehabilitation department was opened at this hospital in 1973 and has treated more than 1,500 patients. It was originally set up to relieve pressure on the general and surgical wards. It admitted elderly patients who required additional treatment or who could not be discharged due to inability to function independently without a suitable support framework. The department has since focused increasingly on rehabilitation of elderly patients following CVA or fracture of the hip, with increasing emphasis on physiotherapy. At the same time, a geriatric facility system of work was consolidated, whose features are a multidisciplinary team, a thorough study of the patient from many aspects, and search for medical, nursing and rehabilitation solutions best suited to the patient's particular needs. Problems encountered in those admitted have recently changed, and patient turnover is now more rapid and duration of hospitalization has shortened. The department had been transformed from a long-stay ward treating chronic illness to one giving intensive treatment following an acute crisis. PMID- 7995564 TI - [Surgical treatment of choledochal cyst]. AB - Our experience with 11 cases of cystic dilation of the biliary tract is reported. 10 children with choledochal cyst were treated by cystduodenostomy (5 cases) and excision of the cyst with hepaticojejunostomy (5 cases). 1 patient who presented with Caroli's disease was not operated. At long term follow-up, all patients except 1 are asymptomatic. A 16-year-old girl who presented with acute pancreatitis 13 years following cystduodenostomy, early in our experience, underwent excision of the choledochal cyst and hepaticojejunostomy, with uneventful postoperative course. We conclude that in the era of modern imaging, accurate preoperative diagnosis may contribute to better planning and outcome of the surgical treatment of these relatively rare congenital biliary anomalies. PMID- 7995565 TI - [Endoscopic treatment of maxillary sinus cysts]. AB - Maxillary sinus cysts are common lesions usually found in routine x-rays of the teeth and sinuses. Although most patients are asymptomatic, there may be headache or periorbital or facial pain. Traditionally, these cysts have been treated by puncture and aspiration, or excision via intranasal antrostomy or Caldwell-Luc operation 23 patients with maxillary sinus cysts who presented with facial pain were treated by endoscopic surgery. During followup of 1 year the cyst recurred in only 1 of the patients (after 2 months). We recommend endoscopic removal of maxillary sinus cysts as the treatment of choice. PMID- 7995566 TI - [Shigellosis in a primary care practice]. AB - The epidemiological and clinical characteristics of 47 patients infected with Shigella in 3436 patients at a primary care clinic during 30 months were reviewed. Most cases were seen during the winter. The prominent clinical features were abdominal pain (91.5%), headaches (72.5%), bloody diarrhea (66%), mucoid stools (63.8%), fever (53.2%) and 75% had 4-10 stools per day. Most patients presented the first day of the illness (75%). S. sonnei has been found the most prevalent among 4 types of shigella. Resistance to ampicillin was complete and to Resprim 95%, but to nalidixic acid and to tetracycline, 4.9%. A third of the patients were treated with oral fluids and an appropriate diet and 2/3 received antibiotics. Children between 1-4 years of age who attend kindergartens are the main risk group for Shigellosis. PMID- 7995568 TI - [Saponins--an easy way to cope with hyperlipidemia]. PMID- 7995567 TI - [Delayed post-anoxic encephalopathy]. AB - A case of the rare condition, delayed postanoxic encephalopathy is presented. This condition occurs after an acute hypoxic insult followed by an interval of apparent full recovery, but relapses to various degrees of renewed neurological impairment, coma or even death. Anesthetists should be aware of this entity and establish proper follow-up in patients at risk. PMID- 7995569 TI - [The allele A1 at the DRD2 locus on chromosome 11--genetic marker for alcoholism]. PMID- 7995570 TI - [Clinical considerations in percutaneous transluminal coronary angioplasty]. PMID- 7995572 TI - [Immunological mechanisms in atherosclerosis]. PMID- 7995571 TI - [Keratinocyte cultures for the treatment of skin ulcers]. PMID- 7995573 TI - [Music and medicine]. PMID- 7995574 TI - [Hypoplastic left heart syndrome: treatment options]. PMID- 7995575 TI - [Pharmacologic therapy of urinary retention after vaginal operations]. PMID- 7995576 TI - [Cardiopulmonary characteristics of elite athletes]. PMID- 7995577 TI - [Advances and "not abused trauma life support" in Israel 1994]. PMID- 7995578 TI - [Dietary fiber--physiological effects and medical applications]. PMID- 7995579 TI - [National survey of antibiotic use after abdominal surgery]. AB - A postal survey of 283 members of the Israeli Association of Surgeons was conducted to determine their current practices as to duration of antibiotic therapy following emergency abdominal operations (response rate 26.5%). The maximal acceptable length of antibiotic administration after various emergency operations was based on recommendations in the recent literature. By these criteria, about half those responding were using excessive courses of post operative antibiotics. We conclude that failure to distinguish between contamination, which requires either minimal post-operative administration of antibiotics or none at all, and infection which requires a proper postoperative course, is the main reason for unnecessarily prolonged postoperative use of antibiotics. PMID- 7995580 TI - [Hirschprung's disease in the Negev]. AB - We treated 65 children with proven Hirschprung's disease between 1970-1992. After definitive surgery, 35 were over 10 years of age and 13 were over 18. The male:female ratio was 4:1. All but 3 were born full-term. 44% were of Bedouin origin, with a higher prevalence in 3 families of 2 tribes. 38 (58%) were diagnosed in the neonatal period: by barium enema and rectal muscle biopsy in 42 (65%), and by barium enema alone in 23 (35%). In the latter the diagnosis was verified by intra-operative biopsy. Severe constipation, intestinal obstruction or enterocolitis were the presenting features. 19 associated anomalies were found in 12 children, but none was life-threatening; 5 (8%) had cardiac anomalies; none had Down's syndrome. The rectosigmoid colon was the most common aganglionic segment involved (only 1 had total colonic aganglionosis). 7 of the 8 with short segment involvement responded well to posterior rectal myectomy. 55 patients had an abdominoperineal pull-through: 48 by Swenson's procedure and 5 by the Soave and 2 by the Duhamel modifications. In 43 a protective colostomy was performed at the end of the procedure. 53 had complete diversion colostomy at the time of initial diagnosis (neonatal and early infancy). There was no intra- or immediate post-operative death. 1 patient died 2 months after operation of complications following enterocolitis and total parenteral nutrition. 2 died a few hours after admission of severe sepsis due to enterocolitis before operation was possible. There were early postoperative complications in 11% of the 151 operations, mostly minor wound infections.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7995581 TI - [Relationship between plasma antioxidants and coronary artery disease]. AB - Plasma concentrations of the antioxidants, vitamin E, beta-carotene and vitamin A were studied. 29 patients in whom at least 70% obstruction of 1 coronary artery was found, and 73 who were normal according to noninvasive tests were compared using multivariable, logistic, regression analysis. The group with coronary disease had significantly lower plasma vitamin E and beta-carotene concentrations as compared with the normal group (means +/- SD: 44.2 +/- 18.3 micrograms/ml vs 50.6 +/- 22.4 and 1.0 +/- 0.5 micrograms/ml vs 1.1, respectively) but plasma vitamin A concentration was not reduced. Decrease in plasma antioxidant vitamin concentrations may be linked to atherogenesis by LDL oxidative modification, which explains the inverse relationship found between the risk of coronary artery disease and plasma antioxidant vitamins. PMID- 7995582 TI - [Fabry disease: systemic deposition of a glycolipid]. AB - A 20-year-old man was admitted with telangiectatic skin lesions over the lower abdomen, buttocks and genitals and also hypohidrosis and heat intolerance. Fabry disease was diagnosed on the basis of biochemical and histopathological analyses. The concentration of urinary trihexosyl-ceramide was increased but the activity of galactosidase in serum, urine and lymphocytes was marginal. Typical lipid inclusions, showing a concentrically arranged, lamellar osmiophilic structure were identified by electron microscopy in the cytoplasm of endothelial cells from affected skin. PMID- 7995583 TI - [Groove pancreatitis and adenocarcinoma of the pancreatic head]. AB - A mass within the head of the pancreas causing obstructive jaundice is frequently adenocarcinoma, or infrequently focal pancreatitis. Groove pancreatitis is an inflammation of the head of the pancreas which fills the anatomic space between the head of the pancreas on 1 side and the second part of the duodenum on the other. Obstruction from either cause may cause vomiting, abdominal pain, and loss of weight. It is sometimes impossible to differentiate between the 2 conditions clinically. We present 2 women, aged 41 and 42 years, respectively, with recent onset of diabetes mellitus, obstructive jaundice, abdominal pain and severe loss of weight in whom diagnosis was difficult. In 1 repeated fine needle biopsy directly from the mass did not show adenocarcinoma, but she died of the disease a few months later. The other, in whom malignancy was also suspected, recovered from what was retrospectively diagnosed as groove pancreatitis. PMID- 7995584 TI - [Sonographic demonstration of pseudo-cholelithiasis after ceftriaxone]. AB - The term biliary pseudolithiasis was coined by Schaad (1988) to describe the appearance of gallbladder sludge following treatment with ceftriaxone. After cessation of the drug the condition resolves, hence the term "pseudolithiasis." The third generation cephalosporin, cefatriaxone, is a very potent, broad spectrum antibiotic indicated in meningitis, osteomyelitis, pyelonephritis, Lyme disease and many other severe infectious diseases. Up to 46% of those receiving this antibiotic develop gallbladder sludge. Most are asymptomatic, but a small proportion may develop right upper quadrant pain, nausea, vomiting and even cholecystitis. Ultrasonography may demonstrate many, small, echogenic particles within the gallbladder, as well as larger echogenic foci casting acoustic shadows. However, it can not differentiate these pseudostones from real stones. There are reports of surgical intervention in such cases. 2 boys, aged 5 and 10 years, respectively, treated with ceftriaxone for meningitis are presented. Both developed symptoms during treatment and in both gallbladder sludge was identified by ultrasonography. In 1 intraluminal gallbladder findings were identical with the appearance of surgical stones. Follow-up ultrasonography after the drug was stopped showed no evidence of pseudostones in either case. Awareness of this phenomena might save many unnecessary operations. PMID- 7995585 TI - [Lithium-associated alopecia]. AB - A 39-year-old woman who developed alopecia shortly after treatment with lithium carbonate was initiated is described. The alopecia resolved 2 months after lithium was discontinued. Though this side-effect is relatively rare, we suggest that patients getting lithium for short or long term treatment be monitored for it. PMID- 7995587 TI - [Fraud and misconduct in medical research]. PMID- 7995588 TI - [Routine vaccination in the elderly--application and effectiveness]. PMID- 7995586 TI - [Ephedrine psychosis]. AB - Ephedrine has both alpha- and beta-adrenergic activity, and both direct and indirect effects on receptors. Its stimulatory effects on the central nervous system are more prolonged, though less potent, than those of adrenalin. It raises blood pressure both by increasing cardiac output and inducing peripheral vasoconstriction. It is still commonly used as a bronchodilator. However, since prolonged use leads to decreased effectiveness, patients tend to increase the dose themselves. The clinical picture of ephedrine psychosis resembles that induced by amphetamines: primarily a paranoid psychosis with delusions of persecution and auditory and visual hallucinations in a setting of unclouded consciousness. We present a 57-year-old woman who had been taking a usual dose of ephedrine for bronchial asthma (50 mg 3 times a day) for more than 30 years. When her husband died she developed depression, for which she tried to use ephedrine as an antidepressive, increasing the dose to 500 to 1000 mg a day over the course of half a year. She developed paranoid psychosis with delusions of persecution and auditory hallucinations, despite a clear sensorium. Recovery was rapid after ephedrine was gradually reduced to 200 mg a day and a small dose (200 mg) of the neuroleptic thioridazine was added. PMID- 7995589 TI - [Radiologic contrast agents and hypoxic renal medullary injury]. PMID- 7995590 TI - [Intraocular metastatic tumors]. PMID- 7995591 TI - [Treatment of open fracture of the tibia and femur, including intramedullary nailing]. PMID- 7995593 TI - [Transient synovitis of the hip]. PMID- 7995594 TI - [Decision-making in Hallux valgus deformity]. PMID- 7995592 TI - [Corticosteroids in sepsis and in shock following sepsis]. PMID- 7995595 TI - [Acute compartment syndrome of the foot]. PMID- 7995596 TI - [Genomic imprinting--a revolution in the understanding of genetic biological processes]. PMID- 7995597 TI - [Vitamins and their influence on the immunological system]. PMID- 7995598 TI - Construction of recombinant K88 DNA with Ptac promoter. AB - The gene encoding K88ab was localized on the 11.6 kb HindIII-HindIII fragment of 74 kb plasmid DNA of E. coli 7301. The smallest recombinant DNA producing the K88ab antigen was obtained by excision of the 5.15 kb EcoRI-EcoRI fragment from recombinant DNA composed of the 11.6 kb K88ab fragment in the pBR322 vector. The size of the smallest fragment was 6.5 kb. Expression of the K88ab antigen was controlled by the P1 promoter of the pBR322 vector. Substitution of promoter Ptac for promoter P1 made it possible to achieve expression of the K88ab antigen by E. coli MT. Substitution of promoter PL for promoter P1 failed to achieve expression of the K88ab antigen in the recipient strains used. PMID- 7995599 TI - Quantitative relationships between structure and antimicrobial activity of new "soft" bisquaternary ammonium salts. AB - New surface-active bisquaternary ammonium salts derived from bis-(2 dimethylaminoethyl) ester of glutaric acid are highly effective against representatives of Gram-positive, Gram-negative bacteria and yeasts. Relationships between structure, lipophilicity and antimicrobial effectiveness were demonstrated by quantitative structure-activity methodology. The non-linear dependence of biological activity on the structure as well as lipophilicity (expressed as critical micelle concentration-CMC) was shown using Kubinyi's bilinear model. The most effective compounds were those with the alkyl chain of 11-12 carbon atoms and with the CMC values around 0.7-1.0 mmol/L. These derivatives possessed higher antimicrobial activity particularly to Gram-negative bacteria. PMID- 7995600 TI - Plasmid profiles of bacteriocin-producing Lactobacillus isolates from African fermented foods. AB - Fourteen of 200 Lactobacillus isolates from African fermented foods, viz. 'wara', 'kenkey', 'ugba', 'ogi', 'kunuzarki', 'fufu' and 'iru' were found to produce bacteriocins against L. plantarum and only three bacteriocinogenic isolates inhibited some of the food pathogens. Plasmid analysis of the 14 bacteriocin producing lactobacilli showed that only 5 isolates harbored plasmids ranging in size from 3.1 to 55.5 kb. PMID- 7995601 TI - Enzymic and permeability activity of Pseudomonas aeruginosa after treatment with sub-MICs of organic ammonium salts. AB - The effects of subinhibitory concentrations (1/4, 1/8, 1/16 of the MIC) of 12 organic ammonium salts of A (hard-alkyltrimethylammonium bromides) and B (soft--2 (dodecanoylamino)ethylalkyldimethylammonium bromides) homologous series on phospholipase C, proteinase, elastase and permeability activity were studied. The substances with longer substituents were more effective in reducing phospholipase C activity (hard and soft series) as well as proteinase (hard series). Phospholipase C was the most frequently and the most markedly inhibited enzyme. The organic ammonium salts were less effective in inhibiting elastase and permeability activity. Only one of the substances under study reduced all the tested activities. PMID- 7995602 TI - [A damping method makes possible a more exact sonographic study of tongue movements]. AB - If the home-made cushioning appliance presented here is placed during ultrasonic examinations between the submental region and the probe head, then the problems caused by probe head movement and pressure on the submental region, as have been encountered in the past, can be solved. The use of such a cushioning appliance makes possible a more accurate B-mode ultrasonic evaluation of tongue function. The prevailing method and the cushioning method presented here were studied on 50 test patients. Comparison of the 2 methods revealed that in fact the use of the cushioning method prevented movement in the ultrasonic probe and also its use hardly impaired the patient's ability to swallow. We therefore recommend that this cushioning method be routinely applied during ultrasonic examinations of tongue function. PMID- 7995603 TI - [Facial morphology and the size and activity of the masseter muscle]. AB - The study presented here was conducted for the purpose of investigating the possible relationship of masseter muscle size and activity to facial morphology. The study examined 50 adults, 25 males and 25 females, by means of electromyography, ultrasonography, and facial photography. The following results were obtained. There was considerable variation in masseter muscle activity and size both between the 2 groups and among individuals in each group. Partly there were strong differentiation's between the males and the females. The interrelationships between masseter muscle activity and size and facial morphology in both groups were generally weak, however, the links were more discernible in the women than in the men. Female subjects with thin faces and large mandibular planes had reduced masseter thickness, whereas women with a small anterior facial height index displayed when relaxed less masseter muscle activity and a smaller masseter width. PMID- 7995604 TI - [A clinical study of the effect of a rigid open activator (ROA) in the treatment of Angle class II.1]. AB - The study introduces a maximally weight and volume reduced rigid open activator (ROA) for wear by patients with Angle class II.1 deformities. The activator is worn from about the age of 9 until the end of the eruption of the permanent canines and the first and second premolars. Intensive wear of the activator leads to regular occlusion after only 4 months. Cephalometric parameters at the beginning of treatment compared with those following regular occlusion document and illustrate the impressive adaptation of the masticatory system achieved through wear of the ROA. PMID- 7995606 TI - [The evaluation of orthodontic treatments. Reflections on the Eismann procedure]. AB - This study presents a broad overview of the fundamental questions involved in evaluating orthodontic treatment methods using a formalized index system. Eismann's numerical success evaluation, which he published 25 years ago and which is an example of this method, is examined in some detail. Both the dividends and limits of the Eismann method are discussed on the basis of our own studies and those of others and modifications to the method are suggested. Not withstanding the limitations inherent in any model based analysis, the Eismann approach is shown to be superior to many similar systems and it thus remains the method of choice for conducting scientific studies of the course of treatment over time. In addition possibilities of further developing and enhancing the method are presented. PMID- 7995605 TI - [Endosseous titanium implants as orthodontic anchoring elements. Experimental studies and clinical application]. AB - Part 1 of this study, which deals with experimental use of titanium implants in animals (Branemark, dimension 10 x 3.75 mm), examines the long-term orthodontic application of force on the quantity of peri-implant and paraimplant bone and on direct bone contact (in %) at the implant surface. In the experiment 6 premolars (P3 mandible/maxilla and P4 mandible) were extracted from each of 2 foxhounds. After 12 weeks each dog received 6 implants (P3 and P4 areas). After the implants had healed for 25 weeks, the fixtures in the P3 areas were used as anchoring elements (test implants) for P2 distalization over a period of 26 weeks (continuous force applied: approximately 2 N). The implants in the P4 area served as the control group. Histological analysis revealed in the test implants (mandible) in comparison to the control implants (mandible) the following differences: broader cortical bone; wider peri-implant bone casing; denser, partly sclerotic spongiosa (pressure side); and thicker trabecula (tension side). Fluorescence microscopy revealed that these findings were the result of distinct lamellar bone apposition during the force application phase. In comparison, far less lamellar apposition was found in the test implants (maxilla). The mean percentage of direct bone contact at the implant surface was: Control implants (mandible, n = 4): 40.5%; test implants (mandible, n = 4): 51.6%; and test implants (maxilla, n = 4): 42.4%. Part 2, the clinical portion of the study, presents the suitability and feasibility of using endosseous implants as orthodontic anchoring elements, first, for orthodontic-prosthetic anchoring, and, second, for orthodontic anchoring only. Further, the significance of these aspects in relation to the implant site, to implant dimension, and to the type of implant anchoring are recorded. PMID- 7995607 TI - [Orthodontics and implantology. Their course and results after joint planning]. AB - The therapeutical repertoire for treating patients with missing teeth was significantly expanded by the development of modern implant methods. We have performed a retrospective analysis covering all children who between 1977 and 1993 had been considered for implants as a method for gap management. All patients were pretreated up to early adolescence using standard orthodontic procedures. Unfortunately, it turned out that an originally planned implant was not suitable in approximately 2/3 of the patients because of inadequate alveolar conditions. These patients were subsequently treated by conventional orthodontic gap closure or adhesive prosthetics. PMID- 7995608 TI - [Moya-moya disease: its physiopathology and surgical treatment]. PMID- 7995609 TI - Computer analysis of Holter electrocardiogram. AB - Computer analysis is indispensable for the interpretation of Holter ECG, because it includes a large quantity of data. Computer analysis of Holter ECG is similar to that of conventional ECG, however, in computer analysis of Holter ECG, there are some difficulties such as many noise, limited analyzing time and voluminous data. The main topics in computer analysis of Holter ECG will be arrhythmias, ST T changes, heart rate variability, QT interval, late potential and construction of database. Although many papers have been published on the computer analysis of Holter ECG, some of the papers was reviewed briefly in the present paper. We have studied on computer analysis of VPCs, ST-T changes, heart rate variability, QT interval and Cheyne-Stokes respiration during 24-hour ambulatory ECG monitoring. Further, we have studied on ambulatory palmar sweating for the evaluation of mental stress during a day. In future, the development of "the integrated Holter system", which enables the evaluation of ventricular vulnerability and modulating factor such as psychoneural hypersensitivity may be important. PMID- 7995610 TI - Angiogenic activity of human villi and decidua in the first trimester of pregnancy. AB - Angiogenic activity in the extracts of human villi and decidua in the first trimester of pregnancy was examined using chorioallantoic membrance assay. Blood vessel density on the chorioallantoic membrane increased greatly with the addition of villi extract, and slightly by decidua extract. Neovascularization with a spoke wheel appearance was induced by both villi and decidua, and this response pattern by the villi was stronger than that by the decidua. Maternal serum did not induce any vascular response. These results suggested that angiogenic activity was present both in the villi and decidua in the first trimester of pregnancy and that the villi activity was stronger than the decidua. PMID- 7995611 TI - [Experimental study on the role of bacteria from urinary tract infections on the bladder carcinogenesis]. AB - The role of bacteria isolated from patients with urinary tract infection (UTI) was studied with a view to the possibility that such bacteria are an etiological factor in the development of bladder cancer. The bacterial strains of Escherichia coli, Pseudomonas aeruginosa, Proteus mirabilis, Serratia marcescens, Staphylococcus epidermidis and Enterococcus faecalis, isolated from patients with UTI at the Kyushu University Hospital, were tested for their nitrate-reducing activity after 1 hr of incubation with sodium nitrate (3.57 mM) in a growth medium (pH 7.2) at 37 degrees C. Of 35 strains tested, 27 strains (77%) showed the ability to reduce nitrate to nitrite with yields ranging from 2 to 310 microM NO2-/hr/10(7) bacterial cells, but in 8 strains (23%) including all the 7 strains of E. faecalis no elevated activity (0.0-0.3 microM) could be detected. Various kinetic profiles were observed for the nitrate-reducing bacteria, at various rate ranging from rapidly to slowly, during 5 hr of incubation. The effect of nitrate reducing bacteria on mutagen formation in the human urine was examined. The mutagenic activity of smokers' or non-smokers' urine incubated with or without bacteria for 72 hr at 37 degrees C was assayed by the Ames Salmonella/microsome test (using TA100 or TA98 with S9-mix). The mutagenic activity increased in urine incubated with the nitrate-reducing S. marcescens or P. aeruginosa, compared to controls which were incubated without bacteria. Potent mutagenic activity could be induced when the urine concentrate prepared from smokers' urine with an XAD-2 resin column was incubated with sodium nitrite (40 mM) at pH 3 for 4 hrs. The potent mutagenic activity observed here seems to be due to the class of direct acting mutagen(s), because no metabolic activation was required. The mutagen formation at an optimal pH 4 proceeded rapidly during 4 hrs of incubation, but decreased thereafter. It was noted that even at a physiological pH 6 of human urine, a lower but significant level of mutagenic activity could still be detected. The mutagenic activity of individual urine concentrate from 14 male smokers and from 6 male non-smokers was assayed after 30 min of incubation with or without sodium nitrite (40 mM) at pH 6. Mutagenic activity increased in most of these urine concentrates incubated with sodium nitrite. The levels were variable between individuals with a 1.3- to 53-fold increase compared with the controls incubated without sodium nitrite.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 7995612 TI - Metabolism of 5 alpha-androstane-3 beta,17 beta-diol in bald and hairy areas of the scalp. AB - In androgen target tissues, testosterone undergoes extensive biotransformation to 5 alpha-dihydrotestosterone which in turn is metabolized into 5 alpha-androstane 3 alpha,17 beta-diol and 5 alpha-androstane-3 beta,17 beta-diol. From studies mainly in the prostate, it has been shown that 5 alpha-androstane-3 beta, 17 beta diol can be further converted to 5 alpha-androstane-3 beta,6 alpha(beta)/7 alpha(beta),17 beta-triols. The present studies show that among the metabolites of 5 alpha-androstane-3 beta,17 beta-diol in scalp homogenates, three were isolated by thin-layer chromatography and identified against standard steroids: 5 alpha-dihydrotestosterone, epiandrosterone, and 5 alpha-androstanedione. Another peak was observed near the origin with a greater polarity than 5 alpha-androstane 3 beta,17 beta-diol. The chromatograms obtained by incubating 5 alpha-androstane 3 beta,17 beta-diol with scalp and prostate homogenates are similar, and it is known that the polar metabolites in the prostate are 5 alpha-androstane-3 beta,6 alpha(beta)/7 alpha(beta),17 beta-triols, suggesting that these steroids are formed in both tissues. In addition, the similarity of chromatograms and mass spectra, obtained when 3 beta-diol polar metabolite(s) and authentic 5 alpha androstane-3 beta,7 beta,17 beta-triol were subjected to GC/MS, confirms this hypothesis. The dependence of the formation of polar metabolites on the substrate (5 alpha-androstane-3 beta, 17 beta-diol) concentration (50 nM-1.3 microM) was studied and resulted in saturation and linear Lineweaver plots from both bald and hairy areas of the scalp.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7995613 TI - Prenatal testosterone levels in XXY and XYY males. AB - It has been postulated that behavioural differences between normal males and those with an additional X or Y chromosome may be related to pre- or postnatal hormonal variations. The prenatal hormone status was investigated using amniotic fluid obtained at antenatal diagnosis between 16 and 20 weeks gestation from fetuses with sex chromosome abnormalities and from controls of the same gestational age. After log transformation, the (geometric) mean testosterone levels were XY 439.4 pmol/l, range 165-1,027 (n = 29), XYY 490.7 pmol/l, range 224-1,092 (n = 20); and XXY 419 pmol/l, range 87-1,021 (n = 20). There were no significant differences between the three male groups and all three were significantly higher than the XX fetuses at 147.0 pmol/l, range 41-474 (p < 0.001). These findings give no support to the hypothesis that prenatal testosterone levels contribute to later behavioural characteristics. PMID- 7995614 TI - Sympathetic-adrenergic activity and acid-base regulation under acute physical stress in type I (insulin-dependent) diabetic children. AB - To evaluate the efficacy of the acute-physical-stress response, plasma catecholamine and lactate levels, serum electrolytes, fructosamine, blood glucose and acid-base status were measured in insulin-dependent diabetes mellitus (IDDM) children and the data compared to those of healthy controls. Four groups were studied: group 1, healthy controls; group 2, newly diagnosed diabetic patients with an IDDM duration of 2-4 weeks; group 3, with an IDDM duration of 5-7 years; group 4, with an IDDM duration of 10-13 years. According to their fructosamine levels, IDDM children were in a well-controlled metabolic state. The physical stress was induced by 1.5-1.7 W/kg/10 min bicycle ergometer determined by a target pulse rate of 170/min. IDDM children exhibited pronounced lactic acidosis under stress (pH: group 2, 7.27 +/- 0.07; group 3, 7.28 +/- 0.05; group 4, 7.20 +/- 0.04, vs. group 1; 7.34 +/- 0.03). Baseline plasma norepinephrine and epinephrine levels showed a significant decrease parallel to the duration of IDDM. Stress induced an increase in the concentration of norepinephrine in each group, but the elevation was significantly higher in the IDDM children versus the controls. A significant negative correlation was found between pH and maximal plasma norepinephrine levels (y = 7.3-0.006x, r = -0.46, p < 0.02). Stress resulted in blood glucose elevation in 13 patients regardless of their pre exercise blood glucose levels.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7995616 TI - Final height in sexually precocious girls after therapy with an intranasal analogue of gonadotrophin-releasing hormone (buserelin). AB - Twenty-two girls affected by sexual precocity with impaired final height prognosis were followed until they achieved final height. Twelve of them were treated with an intranasal (D-Ser6)-gonadotrophin-releasing hormone (GnRH) analogue (buserelin) administered at a mean dose of 25 micrograms/kg/day (range 20-32) for a mean period of 14 months (range 8-18). Ten girls refused treatment. Mean final height of the treated girls was 157.3 +/- 8.2 cm, significantly (p = 0.03) higher than the 149.7 +/- 5.5 cm of untreated patients. Treated girls surpassed midparental height (+1.7 cm) while untreated girls reached the lower part of target zone (-3.5 cm). Our data suggest that intranasal buserelin treatment preserves final height in girls with sexual precocity and initially impaired height prognosis. PMID- 7995615 TI - Expression of aberrant estrogen receptor mRNA in endometrial cancers in comparison with normal endometria. AB - In endometrial cancers, some overexpression of estrogen receptor (ER) mRNA occurred in comparison with the ER mRNA level in normal endometria. DNA binding domains (DBDs) of ER mRNA were detected in 100% (13/13) of the endometrial cancers, and a mutated ER-DBD mRNA was found in 3 of the 13 by S1 nuclease protection analysis. It is suggested that estrogen might lead to disorder in the promotion of estrogen-inducible proteins in these 3 endometrial cancers, which seem to have a point-mutated DBD of the ER and a functional steroid-binding domain, resulting in the dedifferentiation of the original cells, and that the development and growth of cancer cells might, in part, be driven by estrogen. PMID- 7995617 TI - Subcutaneous growth hormone administration in growth-hormone-deficient children. Continuous plus pulsatile overnight versus single daily injection: effects on growth rate velocity. AB - The aim of this study, performed in 10 children, was to verify if a treatment schedule, better reproducing the growth hormone (GH) physiological pattern, could achieve a greater growth response than daily s.c. administration in previously successfully treated children with an isolated idiopathic GH deficiency. A 1 month washout period was observed between the previous regimen and this study. GH (0.6 U/kg/week, the same as given previously) was administered weekly in 6 equal doses. Three children received the daily dose by a single s.c. administration (at 20.00 h) and the other 7 through a 27-gauge infusion needle inserted s.c., using a mini infusion pump permitting a constant delivery of 50% of the daily dose (20.00-08.00 h) and the administration of the other 50% through 3 equal pulses (at 20.00, 24.00, and 04.00 h). After 6 months each child changed regimen undergoing the other one with a 1-month washout interval. During the 12 months of therapy, the mean height increased from -3.2 (SE 0.45) to -2.8 (SE 0.37) SDS. When evaluating the circulating insulin-like growth factor-I pattern as well as the growth velocity and the ratio bone age increase/height age increase, no differences were noted between the two treatment regimens. PMID- 7995618 TI - Adult height in Turner syndrome: results of a multinational survey 1993. AB - Under the auspices of ESPE/LWPES, a survey on spontaneous adult height in patients with Turner syndrome was conducted in 12 European countries. A total of 661 patients (45,X = 51%) with a median age of 23.6 years (range: 16-63) who had never received any growth-promoting treatment until the age of 14 had reached a mean height of 144.3 +/- 6.7 cm. There was no height difference between those (n = 220) who had received oxandrolone and/or estrogen after the age of 14 years and those (n = 441) who never received any treatment until the age of 20. On average, there was no major gain in height after an age of 16 years. The height achieved was positively associated with the height of normal women in the underlying population. There was a high positive correlation (r = 0.436; p < 0.0001) between adult height and target height in adults never treated. A positive correlation of these parameters was present irrespective of karyotype (45,X vs. 'others') or treatment with oxandrolone/estrogen. The findings strengthen the observations on height development from national studies. PMID- 7995619 TI - Effects of growth hormone administration on neurotensin release in children with growth delay. AB - Neurotensin (NT), a tridecapeptide originally isolated from bovine hypothalamus, has numerous actions on endocrine functions. Since intravenous injection of NT in the rat stimulated the release of growth hormone (GH) among several pituitary hormones, the aim of our study was to investigate in humans the effects of GH injection on NT plasma levels. Plasma samples were obtained from 13 children with growth delay (7 boys and 6 girls; age range 5 years 1 month-14 years 1 month; mean +/- SE 10 years 9 months +/- 7 months) to evaluate NT and GH values before treatment and 4, 12 and 24 h after a subcutaneous rhGH injection (0.15 IU/kg). Plasma was extracted on a SEP-PAC C18 column and NT was eluted with propanol. NT concentrations were measured by a specific RIA and expressed as fmol/ml plasma. GH (ng/ml) and somatomedin C (SMC; U/ml) were evaluated by RIA using commercial kits. Free fatty acids (FFA; mEq/l) were measured using a colorimetric peroxidase technique. Before GH administration, NT levels were 7.19 +/- 1.01 fmol/ml. A significant increase in NT values was found 4 h (36.5 +/- 9.62, p < 0.001), 12 h (40.85 +/- 6.64, p < 0.001) and 24 h (19.5 +/- 3.48, p < 0.05) after GH injection. This increase was significantly correlated with the circulating GH levels 4 h after GH administration and with the circulating SMC levels 24 h after GH administration. No correlation was found between NT and FFA values.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7995620 TI - Association of salt sensitivity in rats with genes of the major histocompatibility complex. AB - Dietary sodium intake has long been considered an important factor in the genesis and maintenance of hypertension in both humans and experimental animals. To identify the possible association between salt sensitivity and genes of the major histocompatibility complex (RT1 complex), we studied the blood pressure response to an 8% NaCl diet in normotensive Lewis rats, spontaneously hypertensive rats (SHR), and Lewis.1K congenic rats (congenic to Lewis with the SHR main histocompatibility complex RT1). During the first 4 weeks of a high salt diet, the blood pressure increase was the same in SHR and Lewis.1K congenic rats. Thus, the presence of a small segment of SHR chromosome 20 with genes of the RT1 complex (and closely related genes) in the Lewis genome sensitized the blood pressure of these animals to the hypertensive effects of a high salt diet. Genes of the RT1 complex influenced the salt-induced increase of relative kidney weight more than that of relative heart weight. Our results support the hypothesis that some alleles within or close to the RT1 complex might be responsible for the higher sensitivity of hypertensive individuals to certain environmental stressors, including high salt intake. PMID- 7995621 TI - Beta-adrenergic neuroeffector mechanisms in cardiac hypertrophy of renin transgenic rats. AB - We studied neuroeffector defects in hypertrophied myocardium of hypertensive transgenic rats harboring the mouse Ren-2d gene. In transgenic rats, epinephrine and neuropeptide Y concentrations were reduced. A heterologous desensitization of adenylyl cyclase was observed, which was accompanied by a downregulation of beta 1-adrenergic receptors, an increase of inhibitory G protein alpha-subunits, and a mildly depressed catalyst activity of adenylyl cyclase, whereas the bioactivity of stimulatory G protein alpha-subunits and beta 2-adrenergic receptors was unchanged. Desensitization of adenylyl cyclase was accompanied by a reduced positive inotropic response to isoproterenol, whereas the effect of Ca2+ was unchanged. We conclude that sympathetic neuroeffector defects occur in transgenic rats similar to those observed in human failing myocardium. These alterations occur in the stage of hypertrophy and could contribute to contractile dysfunction in later stages. PMID- 7995622 TI - Genetic and environmental influences on blood pressure in elderly twins. AB - We used 289 pairs of Swedish twins reared apart or together to evaluate the importance of genetic and environmental influences on blood pressure. Unlike other twin and family studies, the adoption/twin design allows a distinction between estimates of the importance of shared rearing environments and genetic effects. Genetic factors were observed to play an important role for individual differences in blood pressure. Model-fitting analyses suggested upper limits of heritability for systolic and diastolic blood pressures in the entire sample of 0.44 and 0.34, respectively. More interestingly, substantial influences of shared family effects accounting for up to 27% of the variation were also revealed. Effects of correlated environment, which might reflect, for example, the intrauterine environment, existed to some extent later in life. The influence of genetic factors tended to decrease across age groups for systolic blood pressure (0.62 in individuals less than 65 years old; 0.12 in those 65 years and older) but not for diastolic blood pressure (0.22 for the middle-aged group; 0.26 for the older group). However, this declining trend for systolic blood pressure did not reach significance (chi 2 = 8.07, df = 4, P = .09). PMID- 7995623 TI - Role of the renin-angiotensin system in neointima formation after injury in rabbits. AB - We investigated the role of the renin-angiotensin system in neointima formation in a species in which converting enzyme inhibitors have been so far ineffective in suppressing abnormal vascular repair. The effects of converting enzyme inhibition by perindopril and selective blockade of angiotensin subtype 1 receptor by DuP 753 were assessed on neointima formation after balloon injury of rabbit carotid artery. Myointimal growth was measured by histomorphometric analysis. In rabbits treated 6 days before and for 14 days after injury, perindopril (2 mg/kg per day PO, n = 7) significantly reduced neointima formation (-51%, P < .01). DuP 753 (1 mg/d, n = 8) infused perivascularly for 14 days in the vicinity of injured carotid artery also markedly suppressed myointimal thickening (-60%, P < .01). To determine whether angiotensin subtype 2 receptor was implicated in this vascular response, we infused CGP 42112A, a specific subtype 2 receptor ligand, continuously for 14 days according to the same protocol of DuP 753 administration. CGP 42112A (1 mg/d) did not change the neointima-media ratio, indicating that angiotensin subtype 2 receptors were not involved in myointimal hyperplasia in rabbits. Thus in rabbits, the renin angiotensin system plays a major role in neointima formation, and the protective effect of perindopril appears to be mediated mainly by inhibition of angiotensin II production, because blockade of the subtype 1 receptor reduced myointimal growth in a manner similar to that of converting enzyme inhibition and because intracarotid infusion of angiotensin II (500 ng/min) at the site of injury enhanced the vascular response (+39%, P < .05). Bradykinin (500 ng/min) administered in the same conditions as angiotensin II did not modify neointima formation. PMID- 7995624 TI - Effects of insulin on vascular responses to mental stress and norepinephrine in human forearm. AB - Essential hypertension is frequently associated with insulin resistance and hyperinsulinemia. In vitro, insulin has vasodilator actions, but its possible hemodynamic effect on muscular vascular beds in humans is a matter of controversy. We investigated the effects of local hyperinsulinemia on the vascular responses to norepinephrine and physiological vasodilation during mental stress in the perfused-forearm model. Nine glucose-tolerant, normotensive, nonobese men (aged 22 to 36 years) participated. Forearm perfusion studies (venous occlusion plethysmography) were performed during randomized, double-blind intrabrachial artery infusions of insulin (to raise plasma insulin 100 microU/mL) or placebo for 2 hours. A mental stress test and stepwise intra-arterial infusion of norepinephrine (6 to 1200 ng/min) were performed during each infusion. Insulin infusion increased venous plasma insulin to 98.4 microU/mL and increased net glucose uptake threefold. Insulin had a gradual vasodilator effect (P < .05 by ANOVA), and after 90 minutes blood flow was 36 percent units higher relative to the control arm than during placebo (P = .005). During mental stress, forearm blood flow increased by 81% (t test, P = .006) and 92% (P = .01) in the study arm during insulin and placebo infusions, respectively (insulin versus placebo, P = NS). An increased forearm blood flow was maintained throughout the mental stress test during insulin infusion (ANOVA, P = .03). Forearm glucose uptake increased during stress, reflecting forearm hyperperfusion since fractional glucose extraction was unaffected by stress. The increased blood flow was maintained throughout the five norepinephrine dose steps (ANOVA, P < .04).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7995625 TI - Additive effects of obesity, hypertension, and type 2 diabetes on insulin resistance. AB - Resistance to insulin-mediated glucose disposal has been previously shown to be increased in association with obesity, high blood pressure, and non-insulin dependent diabetes mellitus. We initiated the present study to quantify the separate effects of hypertension and non-insulin-dependent diabetes mellitus on insulin resistance in both nonobese and obese subjects. To accomplish this, 88 subjects were divided into the following five experimental groups: normal blood pressure, nonobese (n = 17); normal blood pressure, obese (n = 18); high blood pressure, nonobese (n = 18); high blood pressure, obese (n = 19); and high blood pressure, obese, non-insulin-dependent diabetes mellitus (n = 16). Plasma glucose and insulin concentrations were measured before and after a 75-g oral glucose load. Resistance to insulin-mediated glucose disposal was estimated by determining the steady-state plasma insulin and glucose concentrations during the last 30 minutes of a continuous infusion of somatostatin (5 micrograms/min), exogenous insulin (25 mU/m2 per minute), and glucose (240 mg/m2 per minute). Since the steady-state plasma insulin concentrations are similar in all subjects, the higher the steady-state plasma glucose, the more insulin resistant the individual. Nonobese subjects with normal blood pressure had the lowest plasma glucose and insulin responses and steady-state plasma glucose concentrations, and their values were significantly different from the other four groups. Obese or nonobese subjects with high blood pressure had significantly higher plasma glucose responses and steady-state plasma glucose concentrations than did their respective weight-matched control subjects.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7995626 TI - Refeeding hypertension in obese spontaneously hypertensive rats. AB - Very-low-calorie diets lower blood pressure acutely in obese humans and rats. However, refeeding after dietary restriction produces mild hypertension in rats. Refeeding hypertension was characterized in genetically obese spontaneously hypertensive rats (obese SHR, Koletsky rat), a model of genetic obesity and hypertension. Obese SHR were fed a restricted diet (Optifast) for 12 days, refed ad libitum for 28 days, dieted again for 12 days, and then refed 4 days and killed. Control obese SHR and lean SHR littermates were fed ad libitum continuously. Dietary restriction led to rapid weight loss followed by prompt regain to baseline weight after return to unrestricted food intake. Heart rate fell with institution of the low-calorie diet and returned to baseline on refeeding. Blood pressure became elevated during refeeding in dieted obese SHR relative to ad libitum fed obese SHR controls. The fall in blood pressure after ganglionic blockade with chlorisondamine was exaggerated in refed obese SHR, and cardiac beta-adrenergic receptors were downregulated. Both of these findings imply increased sympathetic tone. The left ventricular wall was thicker in the refed obese SHR than in the ad libitum fed obese SHR. Shorter cycles of weight loss and regain in lean SHR led to transient increases in blood pressure and heart rate. Cycles of dietary restriction and refeeding in obese SHR elicit sustained blood pressure elevation via sympathetic activation and exacerbate cardiac hypertrophy. Drastic fluctuations in nutrient intake may not be advantageous in hypertension. PMID- 7995627 TI - Tyrosine kinase inhibition prevents deformation-stimulated vascular smooth muscle growth. AB - The goal of this study was to determine the role of tyrosine phosphorylation in transducing deformation-stimulated vascular smooth muscle growth. Rat aorta derived vascular smooth muscle cells were cultured on flexible silicone elastomer membranes and subjected to cyclic deformation (15 cycles per minute, deformed 2 seconds, relaxed 2 seconds). Deformation significantly increased proto-oncogene expression, [3H]thymidine incorporation, [3H]leucine incorporation, and cell number. Time course studies showed an 8-hour lag between initiation of cell deformation and onset of [3H]thymidine incorporation, with peak levels achieved after 18 to 24 hours. Western analysis of protein blots from deformed cells (10 minutes) demonstrated increased levels of phosphotyrosine-containing proteins having molecular weights of 110 to 130 and 70 to 80 kD. Deformation-stimulated tyrosine phosphorylation was prevented by the tyrosine kinase inhibitor Herbimycin A. Tyrosine kinase inhibition also prevented deformation-stimulated vascular smooth muscle cell growth as measured by [3H]thymidine incorporation. Cyclic deformation stimulates vascular smooth muscle proliferation through activation of tyrosine kinases. Inhibition of tyrosine phosphorylation is an effective means of preventing deformation-induced vascular smooth muscle growth in vitro. PMID- 7995628 TI - Modulatory effects of endogenous adenosine on epinephrine secretion from the adrenal medulla of the rat. AB - The purpose of this study was to examine (1) whether endogenous adenosine receptors inhibit the release of epinephrine and norepinephrine from adrenal medulla in response to physiological and pharmacological stimuli and (2) whether the renin-angiotensin system modulates this effect of endogenous adenosine. We used a conscious animal model to approximate normal physiological conditions. Male Sprague-Dawley rats were treated with a surface adenosine receptor antagonist, 1,3-dipropyl- 8-(p-sulfophenyl)xanthine (DPSPX) to explore the effect of endogenous adenosine. Plasma epinephrine and norepinephrine levels in response to hydralazine-induced hypotension were measured in these animals. The same protocol was repeated in rats pretreated with either adrenalectomy or captopril. The results showed that DPSPX treatment significantly increased plasma epinephrine and norepinephrine levels at both baseline conditions and after hydralazine-induced hypotension. The results from the adrenalectomized rats showed that the difference in plasma epinephrine level between the control and DPSPX groups originated from the adrenal medulla. Pretreatment with captopril attenuated the rise of plasma epinephrine and norepinephrine levels in DPSPX treated animals. This result suggests that endogenous adenosine receptors inhibit epinephrine release from the adrenal medulla and suppress plasma norepinephrine levels. When catecholamine release was stimulated by physiological and pharmacological stimuli, this inhibitory function of adenosine receptors was augmented. The renin-angiotensin system is at least partially responsible for the modulatory function of endogenous adenosine on the catecholamine response as demonstrated in this study. PMID- 7995629 TI - Impaired leukocyte-endothelial cell interaction in spontaneously hypertensive rats. AB - Hypertension is associated with a progressive organ injury whose etiology remains largely speculative. An increasing database shows that activated leukocytes, while affording an important immune protection, may be a contributing factor to several of the pathogenetic features of the hypertension syndrome. The purpose of this study was to determine the extent to which the glucocorticoid pathway may be involved in the atypical kinetics of leukocytes in spontaneously hypertensive rats (SHR) compared with normotensive Wistar-Kyoto (WKY) rats. The typical venular leukocyte adhesion induced by histamine application was significantly lower in SHR, and a comparison of normalized leukocyte rolling velocity (VWBC/VRBC) showed the values to be significantly higher in SHR relative to WKY controls. This abnormal trend in adherent leukocyte numbers and in VWBC/VRBC values could be counteracted when SHR were pretreated with RU 486, a synthetic glucocorticoid inhibitor, and restored to the levels observed in WKY rats. Anti-P selectin monoclonal antibody (PB1.3) attenuated in SHR and WKY rats the increment of adherent leukocyte numbers as well as the decrement of VWBC/VRBC value that developed under combined histamine and RU 486 superfusion. Furthermore, an anti intercellular adhesion molecule-1 monoclonal antibody (1A29) served to attenuate the increment of adherent leukocyte number induced by a combination of histamine and RU 486 superfusion in WKY rats and SHR. The results indicate that the deficient leukocyte-endothelial cell interaction in SHR can be circumvented by a glucocorticoid inhibitor. PMID- 7995630 TI - Spontaneously hypertensive versus control rat aorta response to neutrophil derived factors. AB - We designed experiments to study the interaction of activated rat peritoneal neutrophils with aortas from spontaneously hypertensive rats (SHR) compared with those from normotensive rats. In aortic rings precontracted with phenylephrine, neutrophils obtained from normotensive rats caused a cell number-dependent relaxation of normotensive rat aorta with or without endothelium, whereas relaxation (at lower concentrations) followed by contraction (at higher concentrations) was observed in SHR aorta with endothelium. In SHR aortic rings denuded of endothelium, neutrophils did not induce contraction. The relaxation might be due to a factor indistinguishable from nitric oxide. The contraction might be due to prostaglandin H2 because it was blocked by indomethacin, a cyclooxygenase inhibitor, and ridogrel, a thromboxane A2 synthetase inhibitor/thromboxane A2-prostaglandin H2 antagonist, but not by superoxide dismutase, a superoxide anion scavenger, or dazoxiben, a thromboxane A2 synthetase inhibitor. SHR neutrophils caused a cell number-dependent relaxation of normotensive rat aorta with or without endothelium, whereas relaxation followed by contraction was observed in SHR aorta with endothelium. In SHR aortic rings denuded of endothelium, neutrophils did not induce contraction. The relaxation might be due to a factor indistinguishable from nitric oxide. The contraction seems to be due to superoxide anion because it was inhibitable by indomethacin and superoxide dismutase but not by dazoxiben and ridogrel. Equivalent amounts of superoxide anion were produced by unstimulated and phorbol myristate acetate-stimulated neutrophils obtained from either SHR or normotensive rats. Therefore, increased production of this anion could not explain the contraction observed in hypertensive aortas.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7995631 TI - Na(+)-H+ exchanger expression in vascular smooth muscle of spontaneously hypertensive and Wistar-Kyoto rats. AB - The Na(+)-H+ exchanger has important modulatory effects on vascular smooth muscle cell proliferation and contractility. Increased Na(+)-H+ exchange activity is a general property of many tissues, including mesenteric artery and cultured vascular smooth muscle cells, in the spontaneously hypertensive rat (SHR). In the present work, we investigated whether alterations in the steady-state levels of specific Na(+)-H+ exchanger mRNA isoforms (NHE-1 through NHE-4) are associated with the observed increases in exchanger activity. Poly(A+) mRNA prepared from 12 week-old hypertensive SHR and normotensive Wistar-Kyoto (WKY) aorta, kidney, and intestine was hybridized to cDNAs specific for each NHE isoform. By Northern blot analysis, NHE-1 was detected in all tissues as well as cultured vascular smooth muscle cells and was not regulated differently in SHR compared with WKY tissues. There was no expression of NHE-2, NHE-3, or NHE-4 in SHR and WKY aortas or in cultured vascular smooth muscle cells from SHR and WKY aortas. Stimulation of NHE 1 mRNA expression by growth factors was similar in cultured SHR and WKY vascular smooth muscle cells. We conclude that the previously observed increase in exchanger activity in blood vessels and cultured vascular smooth muscle cells of the SHR is not caused by induction of the NHE-2, NHE-3, and NHE-4 isoforms or by alterations in steady-state NHE-1 mRNA expression. These findings suggest that posttranslational regulation of the Na(+)-H+ exchanger is responsible for increased activity in the SHR. PMID- 7995632 TI - Racial differences in the age-related increase in left ventricular mass in youths. AB - We determined the factors related to left ventricular mass adjusted for body size in 60 black (mean age, 13 +/- 2 years) and 40 white (mean age, 14 +/- 2 years) normotensive youths. The factors examined included age, sex, systolic blood pressure, diastolic blood pressure, plasma renin activity, plasma aldosterone concentration, and sodium and potassium intake as determined by 24-hour excretion. Sex (beta = 13.3, P < .003), age (beta = 2.88, P < .001), and systolic blood pressure (beta = 0.41, P < .02) were independent predictors in the sample as a whole, accounting for 37% of the variance of left ventricular mass adjusted for height. Separate analyses were performed for black and white subjects. In the black subjects, age (beta = 4.4, P < .004) followed by sex (beta = 11.85, P < .02) were independent factors, accounting for 43% of the variance of left ventricular mass adjusted for height. In contrast, in white subjects systolic blood pressure (beta = 0.4, P < .003) followed by sodium excretion (beta = 0.13, P < .05) were independent factors, with gender (beta = 8.89, P < .07) tending to account for 36% of the variance. Similar results were observed for left ventricular mass adjusted for body surface area. In conclusion, the age-related increase in adjusted left ventricular mass in black but not white youths may in part account for the early development of cardiovascular disease among the black population. PMID- 7995633 TI - Renal hemodynamics in essential hypertension. Racial differences in response to changes in dietary sodium. AB - Previous studies have suggested striking racial differences in hypertension related renal disease. To explore potential mechanisms responsible for these differences, we investigated changes in renal hemodynamics in white and black essential hypertensive patients in response to alterations in dietary sodium. Patients were untreated, age-matched, and blood pressure-matched white (n = 59) and black (n = 22) males with essential hypertension. Studies were conducted on an inpatient metabolic ward and included assessment of blood pressure, urinary sodium excretion, glomerular filtration rate, renal plasma flow, and renal blood flow after 5 days each of high and low salt diets. In response to high dietary salt intake, both white and black patients demonstrated significantly higher mean arterial pressure, renal plasma flow, and renal blood flow, and there were no racial differences in the changes in these parameters. However, whites and blacks differed significantly in glomerular filtration rate, with black hypertensive patients showing an increase in glomerular filtration rate (+17.3 +/- 5.3 mL/min per 1.73 m2, F = 7.586, P = .007) and white hypertensive patients showing no change (-0.2 +/- 3.3 mL/min per 1.73 m2) in response to high dietary sodium. These data demonstrate racial differences in the autoregulation of glomerular filtration rate in response to changes in dietary sodium. These differences suggest that glomerular hyperfiltration in response to a high salt diet may be a mechanism contributing to the racial disparity in hypertension-related renal disease. PMID- 7995634 TI - Natriuretic peptides in the human kidney. AB - We studied the presence of three natriuretic peptides--atrial natriuretic peptide (ANP), human brain natriuretic peptide (BNP), and C-type natriuretic peptide (CNP)--in the human kidney by radioimmunoassay and immunocytochemistry. Immunoreactive ANP, immunoreactive human BNP, and immunoreactive CNP concentrations in six kidneys were 0.12 +/- 0.07 (mean +/- SD), 0.23 +/- 0.08, and 0.37 +/- 0.07 pmol/g wet wt, respectively. Sephadex G-50 superfine column chromatography and reversed-phase high-performance liquid chromatography of kidney extracts revealed a broad peak of immunoreactive ANP comigrating with ANP 28 and urodilatin. Renal immunoreactive human BNP consisted of three components; the major component comigrated with human BNP-32. Renal immunoreactive CNP consisted of at least two components; the major component comigrated with CNP-22, and the minor component eluted in a position similar to that of authentic human CNP-53. Immunocytochemistry showed that immunoreactive human BNP was colocalized with immunoreactive ANP in the segments of distal tubules, whereas immunoreactive CNP was found predominantly in the proximal tubules. These findings indicate that these three natriuretic peptides are present in the human kidney and raise the possibility that they form a renal natriuretic peptide system that participates in the local regulation of sodium and water transport and renal circulation in the human kidney. PMID- 7995635 TI - Renal effects of nifedipine and captopril in patients with essential hypertension and reduced renal reserve. AB - In this study we investigated the short-term effects of calcium channel blockers and angiotensin-converting enzyme inhibitors on renal hemodynamics and the urinary excretion of proteins with different relative mass in subjects with mild to moderate essential hypertension and apparently normal glomerular filtration rate but reduced renal functional reserve. Sixteen subjects underwent the following four treatments: (1) low-protein meal (0.2 g protein/kg body wt), (2) high-protein meal (1.3 g protein/kg body wt), (3) high-protein meal plus oral nifedipine (20 mg), and (4) high-protein meal plus oral captopril (50 mg). Two urine samples were obtained after meals. Blood samples were drawn at the midpoint of each 120-minute urine collection period. Urine and serum were tested for total protein, immunoglobulin G, albumin, alpha 1-microglobulin, retinol binding protein, and beta 2-microglobulin. Glomerular filtration rate and renal plasma flow were assessed by iothalamate and p-aminohippuric clearance, respectively. Compared with the high-protein meal alone, nifedipine elicited a clear-cut increase in the urinary excretion of total protein (+60%, P < .01), immunoglobulin G (+58%, P < .01), albumin (+25%, P < .05), retinol binding protein (+47%, P < .05), and beta 2-microglobulin (+52%, P < .05); captopril decreased the urinary excretion rate of immunoglobulin G (-26%, P < .05), albumin (-22%, P < .05), and beta 2-microglobulin (-34%, P < .05). The ratio between the clearances of immunoglobulin G and albumin was higher after nifedipine (+21%, P < .01) and unchanged after captopril (-9%, P = NS) compared with the high-protein meal alone.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7995636 TI - Long-term infusion of kallikrein attenuates renal injury in Dahl salt-sensitive rats. AB - We investigated whether long-term infusion of kallikrein would attenuate renal injury in salt-induced hypertension in Dahl salt-sensitive rats. A subdepressor dose of purified rat urinary kallikrein (700 ng/d IV) was infused by osmotic minipump for 4 weeks in male Dahl salt-sensitive rats fed a high salt (2% NaCl) diet. This dose did not affect the time-dependent elevation of blood pressure; however, urinary protein excretion was significantly decreased, and glomerular filtration rate was increased. These beneficial effects were reflected morphologically by an attenuation of glomerulosclerotic lesions and tubular injury seen in the hypertensive Dahl salt-sensitive rats. Kallikrein infusion increased urinary excretion of bradykinin and stimulated excretion of cyclic GMP, suggesting that the kallikrein-kinin-prostaglandin and nitric oxide axes were enhanced by rat urinary kallikrein infusion. The alterations induced by kallikrein infusion were potentiated by the concomitant administration of the angiotensin-converting enzyme inhibitor alacepril. These studies indicated that long-term replacement with rat tissue kallikrein attenuates renal injury in hypertensive Dahl salt-sensitive rats. PMID- 7995637 TI - Rise of blood pressure with age. New evidence of population differences. AB - Epstein and Eckoff in 1967 devised a scheme to summarize population differences in the rise of mean values of systolic blood pressure by age in accordance with their slopes and levels. For the first time, the validity of this scheme can be examined with data from a single study, INTERSALT. This study included 52 populations in 32 countries. On the basis of these data, collected in an exceptionally well-standardized mode under a common protocol, the diversity of populations in the slopes of age differences in median values of systolic blood pressure has been strongly reconfirmed. Populations with no increase in median systolic blood pressure were again observed and remained exceptional. The analyses of these data also indicate a positive relation between the slope of rising systolic blood pressure with age and urinary sodium, urinary sodium potassium ratio, and reported alcohol consumption as well as a negative association between urinary potassium excretion and blood pressure slope. The present analyses therefore add to the previous knowledge and results published by the INTERSALT investigators in the following three respects: (1) they relate INTERSALT results to the postulated biological gradient of variation among populations as presented by Epstein and Eckoff, including explanatory variables; (2) they demonstrate strong correlation between ranks of median blood pressure at 40 to 49 years and values at 20 to 29 years; and (3) they therefore support the original Epstein and Eckoff concept of population variation, link this with blood pressure risk factors, and call attention to the large degree of population differences already evident among populations at 20 to 29 years of age. PMID- 7995638 TI - Systematic difference between blood pressure readings caused by cuff type. AB - In this study we determine whether blood pressure readings using a cuff of fixed size systematically differed from readings made with a triple-bladder cuff (Tricuff) that automatically adjusts bladder width to arm circumference and assessed subsequent clinical and epidemiological effects. Blood pressure was measured with a standard cuff or a Tricuff in 454 patients visiting an outpatient clinic in the Seychelles (Indian Ocean). Overall means of within-individual standard cuff-Tricuff differences in systolic and diastolic blood pressures were examined in relation to arm circumference and sex. The standard cuff-Tricuff difference in systolic and diastolic blood pressures increased monotonically with circumference (from 4.7 +/- 0.8/3.2 +/- 0.7 mm Hg for arm circumference of 30 to 31 cm to 10.0 +/- 1.1/8.0 +/- 0.9 mm Hg for arm circumference > or = 36 cm) and was larger in women than men. Multivariate linear regression indicated independent effects of arm circumference and sex. Forty percent of subjects with a diastolic blood pressure of > or = 95 mm Hg measured with a standard cuff had values less than 95 mm Hg measured with a Tricuff. Extrapolation to the entire population of the Seychelles decreased the prevalence of blood pressure greater than or equal to 160/95 mm Hg by 11.5% and 24.0% in men and women, respectively, aged 35 to 64 years. The age-adjusted effect of body mass index on systolic and diastolic blood pressures decreased twofold using blood pressure readings made with a Tricuff instead of a standard cuff.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7995639 TI - Ambulatory blood pressure. An independent predictor of prognosis in essential hypertension. AB - To determine the prognostic significance of ambulatory blood pressure, we prospectively followed for up to 7.5 years (mean, 3.2) 1187 subjects with essential hypertension and 205 healthy normotensive control subjects who had baseline off-therapy 24-hour noninvasive ambulatory blood pressure monitoring. Prevalence of white coat hypertension, defined by an average daytime ambulatory blood pressure lower than 131/86 mm Hg in women and 136/87 mm Hg in men in clinically hypertensive subjects, was 19.2%. Cardiovascular morbidity, expressed as the number of combined fatal and nonfatal cardiovascular events per 100 patient-years, was 0.47 in the normotensive group, 0.49 in the white coat hypertension group, 1.79 in dippers with ambulatory hypertension, and 4.99 in nondippers with ambulatory hypertension. After adjustment for traditional risk markers for cardiovascular disease, morbidity did not differ between the normotensive and white coat hypertension groups (P = .83). Compared with the white coat hypertension group, cardiovascular morbidity increased in ambulatory hypertension in dippers (relative risk, 3.70; 95% confidence interval, 1.13 to 12.5), with a further increase of morbidity in nondippers (relative risk, 6.26; 95% confidence interval, 1.92 to 20.32). After adjustment for age, sex, diabetes, and echocardiographic left ventricular hypertrophy (relative risk versus subjects with normal left ventricular mass, 1.82; 95% confidence interval, 1.02 to 3.22), cardiovascular morbidity in ambulatory hypertension was higher (P = .0002) in nondippers than in dippers in women (relative risk, 6.79; 95% confidence interval, 2.45 to 18.82) but not in men (P = .91). Our findings suggest that ambulatory blood pressures stratifies cardiovascular risk in essential hypertension independent of clinic blood pressure and other traditional risk markers including echocardiographic left ventricular hypertrophy.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7995640 TI - Alcohol abolishes the hypotensive effect of clonidine in spontaneously hypertensive rats. AB - This study tested the hypothesis that concurrent ethanol administration attenuates the hypotensive effect of clonidine. Four groups of spontaneously hypertensive rats matched for baseline systolic pressure and body weight were randomly assigned the following treatments: (1) water (control), (2) ethanol, (3) clonidine, and (4) ethanol plus clonidine for 13 weeks. Ethanol was provided in the drinking water as 5% for 1 week, 10% for the next 2 weeks, and 20% from week 4 to 13. Starting from similar baseline systolic blood pressures, the blood pressure of the control group increased 10 to 15 mm Hg over the 13-week treatment period. A similar rise in systolic blood pressure occurred in ethanol-treated rats despite a drastic (40% to 50%, P < .05) reduction in fluid intake. Clonidine (300 micrograms/kg per day) caused a smaller and shorter reduction in fluid intake. The fluid intake of the combined treatment group was similar to that of the ethanol group. Either treatment caused a significant and additive reduction in body weight gain. Treatment-related mortality (20%) occurred only in the combined treatment group by the 12th week. Clonidine elicited a slowly developing hypotensive response (P < .05) that started 2 to 3 weeks after treatment was initiated and lasted throughout the treatment period. Ethanol abolished the hypotensive effect of clonidine and resulted in blood pressure values that were not significantly different from those of the control or the ethanol group. Blood ethanol concentration was similar in the presence or absence of clonidine (5.5 +/ 1.9 versus 6.5 +/- 3 mmol/L).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7995641 TI - Effects of antihypertensive agents on baroreceptor function in early hypertensive rats. AB - To investigate the effects of antihypertensive treatment with four currently used agents (trichlormethiazide, atenolol, nicardipine, and enalapril) on the arterial baroreceptor function at the early phase of hypertension, we administered the agents to spontaneously hypertensive rats and Wistar-Kyoto rats from 8 to 10 weeks of age and examined the aortic nerve activity function. In untreated spontaneously hypertensive rats, the relation between the arterial pressure and aortic nerve activity was shifted to the right, that is, to a higher pressure level (threshold pressure, 90 +/- 3 versus 76 +/- 1 mm Hg, P < .05), and the maximum gain which was obtained by logistic function analysis was depressed (1.55 +/- 0.08% versus 2.18 +/- 0.13% maximum/mm Hg, P < .01) as compared with untreated Wistar-Kyoto rats. An equivalent decrease in arterial pressure with each of the four agents (-20 +/- 1 mm Hg, P < .01) produced a leftward shift of the arterial pressure-aortic nerve activity relation to a similar extent (threshold pressure, 77 +/- 1 mm Hg, P < .05) in spontaneously hypertensive rats. In addition, treatment with the four agents equally augmented the maximum gain in spontaneously hypertensive rats (2.13 +/- 0.09% maximum/mm Hg, P < .05). The antihypertensive agents affected neither the blood pressure nor the aortic nerve activity in Wistar-Kyoto rats. These findings suggest that antihypertensive treatment with the four classes of agents equally enhances the arterial baroreceptor function through blood pressure reduction but not through specific depressor mechanisms at the early stage of hypertension. PMID- 7995642 TI - Local cardiac renin-angiotensin system and hypertensive heart disease. PMID- 7995643 TI - Consensus report of the European Society of Endodontology on quality guidelines for endodontic treatment. PMID- 7995644 TI - Retreatment decision making by a group of general dental practitioners in Germany. AB - The aim of this study was to evaluate whether retreatment of root fillings was judged necessary or not and which kind of retreatment was preferred among a group of general dental practitioners in Germany. A questionnaire comprising 19 cases of endodontically treated teeth with different case histories and several treatment options was sent to all general practitioners in Gottingen (Germany). The cases included teeth with periapical radiolucencies, pain, apical resorption, under- and overfilling, and unfilled root canals. Results obtained from 43 questionnaires returned indicate that non-intervention or further radiographic monitoring were preferred by the majority of general practitioners in 10 of 19 cases, even in the presence of periapical pathosis. Only five cases were judged to require conservative endodontic retreatment and, in four cases, root resection. The results revealed large inter- and intraindividual discrepancies in the estimation of endodontic retreatment need. PMID- 7995645 TI - Radiographic simulation of a periapical lesion comparing the paralleling and the bisecting-angle techniques. AB - Sixty apical areas of single-rooted teeth were examined in this study. A simulated periapical lesion was produced using an acrylic sphere (diameter 2.0 mm), the surface of which was covered with a thin layer of zinc cement. The sphere was placed in close contact with the apical foramen using a thin orthodontic wire inserted into the apical portion of the root canal. The correctly adjusted parallel projection depicted the simulated lesion with a very low degree of error. Overangulation of the central beam with maintenance of parallelism between tooth and film resulted in a moderate degree of magnification. When correctly adjusted, the bisecting-angle technique produced images with almost the same accuracy as the paralleling technique. Over angulation resulted in most images showing a reduced size of the simulated lesion. Moderate under-angulation most often recorded the correct dimension of the globe. In some cases a magnified image of the sphere was produced. Generally, this was associated with a palatally curved root. The investigation thus clearly indicated that the paralleling technique provides the most reliable information about the extent of a pathological process. PMID- 7995647 TI - A model system for evaluating filing technique. AB - The aim of this study was to develop a model system to demonstrate the pattern of load and how much is applied. A lower molar was mounted on a beam and attached to a mandibular phantom head jaw. A strain gauge fitted to the beam allowed loading of the molar to be recorded, during root canal preparation. Ten operators were asked to instrument the distal root canal; after preparation the operators were shown a graphical representation of the loads applied. This formed the basis of discussion and instruction in filing technique. The operators then repeated the filing. The results showed that prior to instruction operators used a push-pull motion, applying a constant lateral force to the canal wall. After instruction and discussion of the graphical representation of the loads applied the stroke rates used were slower and loads applied were higher (two-sample t-test, n = 10, P < 0.01). The experiment was repeated 1 year later and this showed that the change in technique had been retained. In conclusion, this model system allows visual feedback to the operator and can be used as an aid to teaching filing technique. PMID- 7995646 TI - Evaluation of the antimicrobial effectiveness of citric acid and sodium hypochlorite on the anaerobic flora of the infected root canal. AB - This study was designed to evaluate the antimicrobial effectiveness of 25% citric acid, compared with 2.5% sodium hypochlorite, after time intervals of 5, 15, 30 and 60 min. Anaerobic bacterial species were isolated from infected root canals and categorized according to Gram stain as Gram-positive cocci, Gram-negative cocci, Gram-positive rods and Gram-negative rods. The experimental method used was similar to that proposed by the German Society for Hygiene and Microbiology (DGHM) with slight modifications. Testing revealed that citric acid does demonstrate antimicrobial properties against anaerobic bacteria, especially against cocci, but it is less effective than 2.5% sodium hypochlorite. PMID- 7995648 TI - Changes in patient age and tooth distribution for root canal treatment in a teaching hospital over a 15-year period. AB - This study was undertaken to determine the changing pattern of root canal treatment undertaken by undergraduates in a teaching hospital over a period between 1976 and 1990 in terms of the incidence of root canal treatment, noting particularly changes in the types of tooth treated and in the age distribution of patients receiving treatment. It was found that the pattern of provision of root canal treatment has altered in recent years to involve a greater proportion of multi-rooted posterior teeth. More treatment is also being provided for older patients. The trends are comparable with those that have occurred in general dental practice. PMID- 7995649 TI - Biological perspectives on the non-surgical endodontic management of periradicular pathosis. AB - Differential radiographic criteria are unreliable for the histological diagnosis of periradicular lesions of pulpal origin. It should not, therefore, be assumed that large lesions or lesions with an opaque border are cystic. Even if cystic, or if strands of epithelium are present, the literature supports repair following the removal of the source of the pathosis. In most cases, the aetiological factors are oral contamination through the root canal or degenerating pulpal tissue. Therefore, the mere surgical removal of lesions of pulpal origin without removing the causes through proper root canal cleaning, shaping and obturation, will not result in the healing of the periradicular tissues. In addition to removing effectively the causative factors, environmental changes in the periradicular tissues caused by the process of canal debridement may inherently aid in the demise of epithelium, when present. The salient issues are discussed in light of thorough debridement of the root canal system, coupled with postulated mechanisms for the resolution of lesions displaying epithelial stands or cavities. Likewise, the role of calcium hydroxide and its potential role in the alteration of the periradicular environment is addressed, with support for the repair of large periradicular lesions without surgical intervention. PMID- 7995650 TI - Allergy to sodium hypochlorite during root canal therapy: a case report. AB - Sodium hypochlorite (NaOCl), is the most popular irrigation solution used in root canal treatment but it is known to be an irritant to vital tissues. There have been many case reports dealing with toxic effects of this material. Although the allergic potential of NaOCl has been described in the medical literature, only one case of known hypersensitivity to NaOCl has been reported in the dental literature. In this paper a case is presented, describing both local and systemic adverse tissue reactions, caused by an allergic response, after NaOCl irrigation. PMID- 7995651 TI - Post-thaw sperm motility, cAMP concentration and membrane lipid peroxidation after stimulation with pentoxifylline and platelet-activating factor. AB - Earlier studies have demonstrated that pentoxifylline (PTX) and platelet activating factor (PAF) can significantly improve the motion parameters of post thaw human spermatozoa. This study has investigated the effects of PAF, PTX and their combination on cyclic adenosine monophosphate (cAMP) concentrations and membrane lipid peroxidation (LPO) in post-thaw human spermatozoa. Washed spermatozoa from normal volunteers (n = 10) were cryopreserved in Test-yolk buffer using a standard protocol. After 2 weeks the sperm samples were thawed, washed and incubated with either 1 microM PAF, 3 mM PTX or 0.5 microM PAF plus 1.5 mM PTX. Video sequences were recorded at 0, 30, 60, and 120 min for analysis of sperm motion parameters using the Cell Track Sperm Analysis System. Concentrations of cAMP were assessed by radioimmunoassay, and LPO levels were measured by malondialdehyde-thiobarbituric acid reactivity. Our studies indicate a time-course stimulatory effect with overall maximal stimulation observed in samples treated with the combination of PAF and PTX. The maximal stimulation of percentage motility compared to control was observed at 60 min in samples treated with PAF, PTX, or PAF plus PTX. PAF plus PTX stimulated straight-line velocity (VSL), curvilinear velocity (VCL) and lateral head displacement (ALH) after 30 min incubation. The primary effect of PAF was observed on VSL, while the main effect of PTX was on VCL. cAMP concentrations were 3-fold higher than controls in samples treated with PTX or PAF plus PTX. cAMP concentrations in PAF-treated samples did not differ significantly from controls. No significant differences were observed between any groups for LPO.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7995652 TI - Expression and localization of N- and E-cadherin in the human testis and epididymis. AB - Cellular interactions in the testis and epididymis are an important prerequisite for spermatogenesis and sperm maturation, and involve a well-developed complex of intercellular junctions. Cadherins are cell surface proteins which mediate intercellular Ca(2+)-dependent adhesion and are believed to be fundamentally important for maintaining multicellular structures. In the present study we report the expression of a 135 kDa N-cadherin polypeptide in the human seminiferous epithelium by immunoblotting. The presence of N-cadherin was demonstrated by immunohistochemistry on the surface of spermatogonia and primary spermatocytes, and possibly also around some early spermatids, whereas late spermatids were always negative. Endothelial cells also stained for N-cadherin, whereas peritubular cells and Leydig cells did not. No expression of E-cadherin could be demonstrated in the human testis. In the human epididymis E-cadherin, but not N-cadherin, was expressed and localized to the surface of the principal epithelial cells as shown by immunohistochemistry. These observations indicate that cadherins play an important role in the organization of the seminiferous and epididymal epithelium. PMID- 7995653 TI - Analysis of spermatozoa from the proximal vas deferens of vasectomized men. AB - This study assessed the condition of spermatozoa from the proximal vas deferens of men after vasectomy. The fluids of both proximal vas deferens were collected from 67 vasectomized men by cannulating the vas deferens at the time of vasectomy reversal. Selected sperm parameters were analysed after incubation of the spermatozoa for 30 min at 37 degrees C. Sperm concentration in the proximal vas from vasectomized men (16,312 +/- 21,496 million per ml, geometric mean: 7948 +/- 398 million per ml) was significantly higher than that of fertile men and was maintained at a constant level independent of the duration of vas obstruction. The means of sperm motility (36.2 +/- 26.2%), spermatozoa with normal morphology (50.7 +/- 21.7%), sperm viability (53.0 +/- 25.3%) and hypo-osmotic swelling test (HOS-test, 53.9 +/- 21.7%) were statistically lower than the respective values for normal fertile men. There was no significant correlation between the duration of vas obstruction and the above semen parameters. In 46.4% of vas fluids all spermatozoa were immotile and this condition was more common after 3 years of vasectomy. Immotile spermatozoa in the proximal vas fluids at the time of vasectomy reversal may be an important factor for predicting semen quality and fertilizing ability after vasovasostomy. There were no significant differences in the results of sperm-cervical mucus penetration test (CMPT) between spermatozoa from vasectomized and fertile men. Antisperm antibodies on the surface of spermatozoa from the vas of vasectomized men were determined by the immunobead test (IBT; 78.6% for IgG, 32.1% for IgA) and sperm cervical mucus contact test (SCMC, 36.4%).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7995654 TI - The potential of mild testicular heating as a safe, effective and reversible contraceptive method for men. AB - A preliminary assessment of the contraceptive efficacy of a daily mild increase (1-2 degrees C) in testicular temperature during waking hours is reported in nine couples using two techniques of non-surgical fixation of the testes close to the inguinal canal. With technique 1, immobilization was achieved by passing the penis and the empty scrotum through a hole made in close-fitting underwear; there was one pregnancy, from a man who stopped the heating after 7 weeks, for 42 cycles of exposure in three couples. With technique 2, immobilization was achieved by adding a ring of soft material surrounding the hole in the underwear; there was no pregnancy for 117 cycles of exposure in six couples. Reversibility and safety were assessed. These preliminary results suggest that a daily mild increase in testicular temperature could be a potential contraceptive method for men. PMID- 7995655 TI - Increased 17-OH-progesterone levels following hCG stimulation in men with idiopathic oligozoospermia and raised FSH levels. AB - Leydig cell function was investigated in 71 men with idiopathic oligospermia and compared to 14 fertile controls by assessing the steroidogenic response to GnRH and the repetitive administration of hCG (1500 IU x3). The oligospermic men were divided into two groups according to their basal serum FSH values (FSH < 8, n = 35; FSH > 8, n = 36), this level being defined by the mean + 3 SD of the levels in normal men (3.71 + 4.08 mIU/ml). Oversecretion of LH was supported by the findings of: (a) higher basal LH levels (p < 0.0001) in both oligospermic groups, although still within the normal range; (b) higher Dmax LH and area LH (p < 0.0001) levels in the FSH > 8 group; (c) a strong position correlation (p < 0.001) of the above parameters with the respective levels of FSH. No difference in basal testosterone levels was observed between the three groups, whereas basal levels of 17-OHP were significantly higher (p < 0.05) in the group with FSH > 8. The testosterone/LH ratio was significantly (p < 0.0001) lower in the FSH > 8 group, and was correlated inversely to the basal blood levels of FSH (p < 0.0001) and to the area LH (p < 0.04). After the hCG test, there was no difference in the testosterone and oestradiol response between the groups, whereas the secretion of 17-OHP and the ratio of 17-OHP/testosterone was significantly higher (p < 0.0001) in the group with FSH > 8 compared with the other two groups.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7995656 TI - Pentoxifylline acts synergistically with A23187 to increase the penetration of zona-free hamster oocytes by cryopreserved human spermatozoa. AB - The number of cryopreserved human spermatozoa which penetrated zona-free hamster oocytes after stimulation with 2 mumol A23187 per litre was increased by the further addition of 0.6 or 3.6 mmol pentoxifylline per litre. With spermatozoa prepared by washing by repeated centrifugation, the median numbers of sperm heads/egg were 1.9, 7.9 and 10.8 in the presence of 0, 0.6 or 3.6 mmol pentoxifylline per litre, respectively. A similar effect was observed with spermatozoa prepared on a Percoll gradient. As A23187 inhibited sperm motility, and this was exacerbated by pentoxifylline, the increased penetration rate of hamster oocytes cannot be explained by improved sperm motility. The number of spermatozoa stimulated to acrosome react by 2 mumol A23187 per litre was increased 3-fold by 3.6 mmol pentoxifylline per litre and 4-fold by 5 mmol caffeine per litre. These data suggest that cAMP may act synergistically with Ca2+ to stimulate the acrosome reaction. Pentoxifylline may improve the fertility of poor-quality human spermatozoa by enhancing their ability to respond to the Ca2+ signal produced by binding to the zona pellucida. PMID- 7995657 TI - Assessment of protein synthesis and secretion by rat seminiferous and epididymal tubules in vivo. AB - In vivo microperifusion and micropuncture were used to study tubule protein synthesis and proluminal secretion by the male reproductive tract in vivo. Seminiferous and caput and cauda epididymal tubules were perifused for 3 h. with [35S]-methionine. Perifused interstitial fluid (IF), lumen fluid (LF), and tubule extract (TE) were collected. Proteins were separated by SDS-PAGE, and autoradiograms were developed. Trichloroacetic acid precipitable proteins in each fluid were determined and a protein synthesis index (PSI) was calculated. PSI values demonstrated that the cauda epididymis synthesized less protein in vivo than did either seminiferous or caput tubules. Seminiferous tubules synthesized and secreted into the tubule lumen a relatively constant panel of proteins. Epididymal tubules synthesized and secreted proteins in a region-specific manner. In the caput epididymis the most prominent secreted bands were consistent with the heavy and light chains of epididymal clusterin. In the cauda epididymis, the most prominent synthesized and secreted protein was a 25 kDa protein consistent with the protein D. The above approach to studying protein synthesis and secretion will allow direct study of the physiological and pathophysiological effects on this important epithelial function in vivo. PMID- 7995658 TI - Immunohistochemical localization of proliferating cell nuclear antigen as a tool to study cell proliferation in rodent and primate testes. AB - The immunohistochemical localization of proliferating cell nuclear antigen (PCNA) has become a widely used method for the detection of proliferating cells in cancerous tissues. PCNA expression is maximal around the S phase of the cell cycle. This study has evaluated the applicability of PCNA localization for the analysis of germ cell proliferation in rats, Djungarian hamsters, rhesus and cynomolgus monkeys and men, using Bouin's-fixed, paraplast-embedded tissue. In addition, involuted testes from photoinhibited hamsters, testes from immature rhesus monkeys and from GnRH antagonist-treated rats and cynomolgus monkeys were included. Monoclonal mouse anti-PCNA antibody (clone: PC10) was used for detection of the antigen. Visualization was performed by immunogold-silver staining or avidin-biotin staining. PCNA labelling was confined to the nuclei of spermatogonia and early spermatocytes within the seminiferous epithelium of all species. The distribution of PCNA among the different types of A-spermatogonia in primates is in good agreement with the previously described proliferation pattern of these cells. No staining was observed in resting A-dark spermatogonia, while differentiating A-pale spermatogonia were positive at distinct stages of the seminiferous epithelium cycle. In the rodent species the pattern of labelled A spermatogonia was stage-specific, but agreed only partly with the previously described pattern of mitotic figures of A-spermatogonia. Hormonal withdrawal induced a decrease in the number of PCNA-positive cells in adult rats, hamsters and monkeys. In immature testes from rhesus monkeys positive staining was present in spermatogonia but also in some Sertoli cells, indicating proliferative activity of Sertoli cells in the prepubertal stage.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7995659 TI - Covert coronary disease and non-invasive evidence of covert myocardial ischaemia: their prevalence and implications. PMID- 7995660 TI - Norepinephrine-induced left ventricular dysfunction in anesthetized and conscious, sedated dogs. AB - These studies were conducted to evaluate effects of high dose norepinephrine infusion on left ventricular function in anesthetized and conscious dogs. Separate groups of pentobarbital anesthetized closed-chest dogs received norepinephrine infusion for 90 min followed by 1 h of recovery. Arterial pressure, electrocardiogram, two-dimensional echocardiogram and an equilibrium radionuclide angiogram were monitored. One hour following infusion of norepinephrine, left ventricular ejection fraction was reduced in a dose dependent fashion. Fractional shortening was similarly reduced, with increased left ventricular systolic and diastolic dimensions also observed. Left ventricular end-systolic wall stress was increased at 60 min following infusion of norepinephrine but not saline: saline, 68 +/- 8, norepinephrine, 4 micrograms/kg/min, 113 +/- 8 g/cm2. The left ventricular end-systolic wall stress/fractional shortening relationship showed reduction of contractility. In 10 conscious dogs pretreated with morphine, norepinephrine at 5 micrograms/kg/min x 90 min produced similar changes to those seen in anesthetized animals. Ejection fraction was reduced from 0.69 +/- 0.3 to 0.36 +/- 0.04 at 60 min post infusion. Fractional shortening was also reduced. Left ventricular end-diastolic dimension was increased. However, when animals were followed for 1 week, complete recovery occurred within 48 h. Histology showed mild contraction band necrosis in acute experiments and mild perivascular fibrosis in chronic experiments. Therefore, norepinephrine cardiotoxicity produced significant left ventricular dilation and reduction of ejection phase indices of left ventricular function associated with reduced contractility. In chronic dogs, histologic changes were mild, and left ventricular dysfunction was reversible. PMID- 7995661 TI - Coronary risk factors and silent ischemic heart disease. The ECCIS Project. AB - An epidemiological study was conducted on 5163 men aged 40-59 years, made by occupational samples, from Florence and Rome to identify, by a three-stage procedure, subjects with asymptomatic silent ischemic heart disease (SIHD). This report describes some coronary risk factors. Men who are free from heart disease were compared with: (1) those having a low probability of SIHD (ECG signs only; n = 439); (2) those having a high probability of SIHD (ECG signs plus echographic signs, or positive markers of deficient perfusion, or altered radionuclide ventriculography; n = 104); (3) those having a definite SIHD (signs of the first two groups plus evidence from coronary angiography; n = 25). A clearcut increasing trend in the levels of major coronary risk factors, and in the multivariate estimated coronary risk for major events was found. The difference was not significant between highly probabile and definite cases of SIHD, due to the small numbers involved. Three multiple logistic models, with the three probability levels of silent ischemia as end-points, showed that four of 10 tested factors were associated with the presence of SIHD: age, systolic blood pressure, cigarette smoking and non-HDL serum cholesterol. PMID- 7995662 TI - Silent ischemia after uncomplicated myocardial infarction: lack of incremental clinical significance. AB - To determine the potential utility of the detection of silent myocardial ischemia after acute myocardial infarction for clinical decision making, we investigated the hypothesis that the occurrence of silent myocardial ischemia on ambulatory electrocardiographic (EGG) monitoring after acute myocardial infarction is independently predictive of adverse outcome in patients in whom conventional clinical and investigative parameters indicate favourable prognosis on medical therapy. Among 465 consecutive patients admitted to our Coronary Care Unit with acute myocardial infarction, 42 patients (39% of those eligible) were randomly selected for study. Twenty-four hour ambulatory ECG monitoring was carried out 13 +/- 10 (standard deviation) days post-acute myocardial infarction. Ninety-eight percent of patients were receiving prophylactic anti-ischemic medications and 81% on aspirin. Silent myocardial ischemia was detected in 14%. During the follow-up period of 16 +/- 3 months, acute ischemic events occurred in 33% of those with silent myocardial ischemia and 19% of those without previous silent myocardial ischemia (P = 0.59). The sensitivity of the test for prediction of future acute ischemic events was 22% (95% confidence interval: 3-60%), specificity 87% (95% confidence interval: 72-97%), positive predictive value 33% (95% confidence interval: 4-78%) and negative predictive value 81% (95% confidence interval: 64 92%). Therefore the detection of ambulatory silent myocardial ischemia after acute myocardial infarction is not of sufficient incremental value as a predictor of the occurrence of adverse cardiac events to justify its routine clinical use in this subgroup of patients. PMID- 7995663 TI - Can the electrophysiologic study predict treatment outcome in patients with sustained ventricular tachyarrhythmias unrelated to coronary artery disease? AB - Sustained ventricular tachyarrhythmias unrelated to coronary artery disease are uncommon. Currently there are no clear guidelines to aid selection of the most appropriate treatment strategy. Therefore, factors potentially predictive of arrhythmia recurrence and death and the ability of the electrophysiologic study to predict treatment outcome in patients with spontaneous sustained ventricular tachyarrhythmias unrelated to coronary artery disease were examined in 41 medically treated patients followed for a median of 25 (range 1-76) months. Examined factors were: syncope associated with the spontaneous arrhythmia, the morphology and cycle length of the presenting arrhythmia, underlying ventricular function, cardiac pathology, and the results of drug assessment at electrophysiologic study. Random variability in the ease of arrhythmia induction at electrophysiologic study was measured for the group as a whole and was allowed for in prediction of an effective drug response. The 95% confidence intervals for variability in the ease of repeat arrhythmia induction at the same study were < or = 1 extrastimulus and for variability in the ease of repeat arrhythmia inductions at different studies were < or = 2 extrastimuli. Poisson regression models were used for data analysis. Arrhythmia recurrence was most likely in: (1) patients on treatment not predicted to be anti-arrhythmic at electrophysiologic study; (2) patients whose treatment was not assessable at electrophysiologic study because the arrhythmia was not reliably inducible; (3) patients with impaired ventricular function; and (4) re-entered patients whose arrhythmia had recurred on previously allocated therapy. The risk of arrhythmia recurrence decreased with time from hospital assessment. All five deaths occurred in patients with impaired ventricular function. CONCLUSIONS: drug efficacy should be tested at electrophysiologic study in patients with reproducibly inducible clinical arrhythmias. Treatment not proven to be anti-arrhythmic at electrophysiologic study is usually ineffective. Patients with ventricular dysfunction are at highest risk of death from arrhythmia recurrence and should be considered for an implantable defibrillator, arrhythmia surgery, or heart transplantation if drug treatment is not predicted to be effective or is not assessable at electrophysiologic study. PMID- 7995664 TI - Left atrial dilatation in constrictive pericarditis: a pre and post-operative echocardiographic study. AB - Thirty-three surgically proven cases of constrictive pericarditis were studied pre-operatively by echocardiography for left atrial dilatation and 18 of them underwent post-operative study at a mean follow-up period of 229 +/- 105 days. The degree of left atrial dilatation in these patients was compared with patients of restrictive cardiomyopathy (n = 8) and sex matched controls of similar age (n = 33). Significant left atrial dilatation was present in patients of constrictive pericarditis compared to controls and it was of a similar or greater degree compared to patients of restrictive cardiomyopathy (the left atrium to aorta ratio was 1.7 +/- 0.31, 1.53 +/- 0.18 and 1.07 +/- 0.1, in constrictive pericarditis, restrictive cardiomyopathy and controls, respectively, P = NS for constrictive pericarditis vs. restrictive cardiomyopathy and P < 0.001 for constrictive pericarditis vs. controls). There was no correlation of degree of left atrial dilatation with clinical and hemodynamic variables. Postoperatively, there was regression of left atrial size in patients with normal hemodynamics (n = 12, pre- vs. post-operative left atrium to aorta ratio 1.65 +/- 0.23 vs. 1.32 +/- 0.14, P < or = 0.001) and persisting or increasing left atrial dilatation in patients with persisting hemodynamic abnormality (n = 6, left atrium to aorta ratio 1.66 +/- 0.23 vs. 1.82 +/- 0.15, P = NS). We conclude that significant left atrial dilatation is a consistent echocardiographic feature of constrictive pericarditis. Hemodynamic normalization following successful pericardiectomy is associated with regression of atrial size. PMID- 7995665 TI - Modified Inoue technique for a patient with giant left atrium. AB - Negotiating an Inoue balloon catheter into the left ventricle, in the presence of mitral stenosis, can present a problem when carried out on patients with giant left atrium. We report a manoeuvre to overcome this problem by utilizing the reverse double loop of an Inoue balloon catheter in the large left atrial cavity. PMID- 7995666 TI - Stenosis of pulmonary veins with ventricular septal defect: visualization of the pulmonary veins after pulmonary arterial banding. AB - A case of 'absent' left pulmonary vein with ventricular septal defect was diagnosed based on echocardiography, magnetic resonance imaging and cardiac catheterization at newborn stage. Pulmonary arterial banding was performed at the age of 1 month to ameliorate the pulmonary flow. At a cardiac catheterization 1 year later, the left pulmonary veins were visualized with moderate stenosis at their entrance into the left atrium. The patient has been stable after surgical repair of the ventricular septal defect and dilation of the pulmonary venous stenosis. PMID- 7995668 TI - A comparison of selected communication, social, situational, and individual factors associated with alcohol and other drugs. AB - This study examined selected communication, social, situational, and individual factors associated with alcohol and other drugs. High school students' perceptions of these substances were analyzed to compare alcohol and other drugs. The largest effects involved communication processes. For alcohol, students knew more strategies for resisting offers, had more ability to take the perspective of alcohol offerers, were more likely to receive simple offers, and were more likely to be able to resist them. Social, situational, and individual factor effects were more moderate, showing less perception of risk for alcohol, more pressure to use, more difficulty refusing, and greater, and more frequent consumption. PMID- 7995667 TI - Multivariate prediction of spontaneous repetitive responses in ventricular myocardium exposed in vitro to simulated ischemic conditions. AB - Guinea-pig ventricular myocardium was partly exposed to normal Tyrode's superfusion and partly to altered conditions (using modified Tyrode's solution) set to simulate acute myocardial ischemia (PO2 80 +/- 10 mmHg; no glucose; pH 7.00 +/- 0.05; K+ 12 mM). Using a double-chamber tissue bath and standard microelectrode technique, the occurrence of spontaneous repetitive responses was investigated during simulated ischemia (occlusion) and after reperfusing the previously ischemic superfused tissue with normal Tyrode's solution (reperfusion). In 62 experiments (42 animals) the effects of: (1) duration of simulated ischemia (1321 +/- 435 s), (2) stimulation rate (1002 +/- 549 ms) and (3) number of successive simulated ischemic periods (occlusions) (1.58 +/- 0.92) on: (1) resting membrane potential, (2) action potential amplitude, (3) duration of 50 and 90% action potentials and (4) maximal upstroke velocity of action potential were studied. All variables were considered as gradients (delta) between normal and ischemic tissue. Both during occlusion and upon reperfusion, spontaneous repetitive responses were coded as single, couplets, salvos (three to nine and > 10) or total spontaneous repetitive responses (coded present when at least one of the above-mentioned types was seen). The incidence of total spontaneous repetitive responses was 31% (19/62) on occlusion and 85% (53/62) upon reperfusion. Cox's models (forced and stepwise) were used to predict multivariately the occurrence of arrhythmic events considered as both total spontaneous repetitive responses and as separate entities. These models were applicable since continuous monitoring of the experiments enabled exact timing of spontaneous repetitive response onset during both occlusion and reperfusion. In predicting reperfusion spontaneous repetitive responses, total spontaneous repetitive responses and blocks observed during the occlusion period were also considered. Total occlusion spontaneous repetitive responses were predicted by: (1) longer delta 50% action potential duration (t = 2.68), (2) shorter delta 90% action potential duration (t = -2.17) and (3) fewer occlusive periods (t = 2.46). Total reperfusion spontaneous repetitive responses were predicted by a longer delta action potential amplitude (t = 2.18). Due to few events during occlusion, prediction of individual arrhythmic entities was not possible. Upon reperfusion single spontaneous repetitive responses were predicted by longer delta maximal upstroke velocity of action potential (t = 2.59) and shorter delta 90% action potential duration (t = -2.55); couplets were predicted by longer delta 50% action potential duration (t = 3.26); longer delta action potential amplitude predicted salvos (> 10) (t = 3.26).(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 7995669 TI - Circumstances surrounding needle use transitions among injection drug users: implications for HIV intervention. AB - Injection drug users (IDUs) are at increased risk of infection with the human immunodeficiency virus (HIV). Intervention programs aimed at reducing the spread of HIV in this population typically incorporate a range of risk reduction strategies, including encouragement to move from injection to noninjection. However, very little is known about the factors associated with needle use transitions, either spontaneous or in response to intervention. We report a study in which a cohort of IDUs were asked about the reasons they stopped and restarted injection. Of 855 IDUs, 179 (21%) had had a least one 12-month period of noninjection since they first injected. Almost one-half of the reasons given for stopping injecting related to personal crises, characterized by major shifts in attitude to drugs and/or life more generally, and often generated by pressures in significant relationships. Concerns about HIV were cited by only one respondent. Many of the factors associated with transition out of needle use in the study population are not readily amenable to intervention. The implications of this for HIV risk reduction programs are discussed. PMID- 7995670 TI - Childhood abuse of parents of alcohol and other drug misusing adolescents. AB - Parental history of childhood physical/sexual abuse was examined among 68 parents of hospitalized middle-class adolescent alcohol/drug misusers and 68 parents of comparable nonhospitalized adolescents. Childhood physical and/or sexual abuse was reported by 54% of control and 48% of patient mothers and 46% of patient and 47% of control fathers, nonsignificant group and gender differences. Abused as compared to nonabused parents reported significantly greater alcohol dependency, more lifetime medical and childhood hyperactivity symptoms, lower levels of socialization, and greater levels of verbal ability, neuroticism, and addiction proneness. PMID- 7995671 TI - The politicization of alcohol in the USSR and its impact on the study and treatment of alcoholism. AB - Conducting research, particularly social science or health-related research, in the former Soviet Union was difficult because of the intrusion of communist ideology on public policy, theory, research, and practice. This report provides a description of drinking and alcohol-related problems in Siberia that was not previously available for publication. It reviews how the Soviet State's policies effected the study and treatment of alcoholism in Russia, and presents a critical review of these policies that would not have been permitted under the previous regime. PMID- 7995672 TI - Drug treatment decisions of chemically-dependent women. AB - The Cognitive Appraisal Model was developed as a means of examining the cognitive appraisal processes and the intervening variables that affect the decision of chemically-dependent women (CDW) to remain in or drop out of a drug treatment program. Methodological triangulation, in which eight questionnaires were selected as construct measures, was used to compare a group of CDW who remained in treatment 4 consecutive months (N = 39) and a group who dropped out prior to completing 4 consecutive months (N = 41). Anger was the strongest predictor of treatment dropout, and feeling inconvenienced by treatment demands ironically predicted treatment compliance. Overall, findings revealed that CDW appraise drug treatment decisions differently than would be expected. PMID- 7995673 TI - Smokeless tobacco consumption by Mexican-Americans and Anglo-Americans in southwestern New Mexico. AB - A telephone survey was conducted to compare the extent of smokeless tobacco consumption by Anglo-Americans and Mexican-Americans. Using systematic random sampling, one out of every 25 phone numbers was selected from the Grant County, New Mexico, telephone directory. Two hundred and ten individuals were interviewed. All of the female respondents, including 46 Mexican-Americans and 81 Anglo-Americans, indicated that they did not use smokeless tobacco. Twenty-five percent of the 51 Anglo-American males and 26% of the 30 Mexican-American males identified themselves as consumers of smokeless tobacco. A chi-square analysis revealed no significance difference between the number of Mexican-Americans and Anglo-Americans among the male self-identified users of smokeless tobacco. PMID- 7995674 TI - The Behavioral and Attitudinal Modification Project (BAM): a failed experiment using a classical experimental research design in a closed institutional setting for drug addicts. AB - Failure in program implementation and related research within closed institutional settings has long been a source of discouragement for correctional administrators and correctional researchers. This paper describes an attempt to implement an innovative treatment program, The Experimental Behavioral and Attitudinal Modification Project, within a civil addict treatment facility to enhance treatment effectiveness. It documents the major obstacles to correctional program innovation and research which ultimately brought about disruption, complacent cooperation, and other implementation problems leading to a project shutdown. It also attempts to place in theoretical perspective the reasons behind implementation failures, particularly as they relate to innovations in treatment and the use of classical experimental designs in closed institutional settings. The article is adapted from the executive summary of the final report to the funding agency. Researchers working to facilitate the effective reintegration of drug-using offenders into society should take heed from this research project, originally implemented in 1970, as a study in FAILURE as apropos today as it was over two decades ago. PMID- 7995675 TI - Comparing the ICAS and the MAC as Indirect Alcoholism Scales: methodological considerations and implications for further research. AB - Four groups of domiciliary residents were studied with the Institutionalized Chronic Alcoholic Scale (ICAS) and MacAndrew Scale (MAC) to determine the more effective indirect alcoholism scale. The groups included: (a) 48 alcoholics, (b) 27 residents with alcoholism and other psychiatric diagnoses, (c) 24 residents with psychiatric diagnoses only, and (d) 22 with only medical diagnoses. MacAndrew had omitted two alcohol usage items from the 51 item MAC in order to develop a more effective indirect scale, free of alcohol usage items. A similar omission technique was employed with the ICAS in the current study. ANOVA indicated that the MAC was the more effective indirect scale. PMID- 7995676 TI - Glycosaminoglycan chondroprotection: pharmacological vistas. AB - Chondroprotection is a somewhat new field in the therapy of osteoarthritis, which is designed to improve cartilage repair as well as enhance joint remodeling. It clearly results from both laboratory models as well as from studies on human osteoarthritis, that cartilage contains biological resources to meet the repair of degenerative injuries and inflammation. Interestingly, sulfated glycosaminoglycans from matrix inhibit leukocyte protease and complement-mediated immunological reactions. By fractioning cartilage glycosaminoglycans from Selachus (Matrix), evidence has been obtained that a proper chondroitinsulfate sequence, which is able to inhibit elastase, may be released from cartilage proteoglycans by cleavage of the xyl-ser O-glycosidic bond. Since a number of sulfated glycosaminoglycans have a regulatory function in an array of tissues, attention is drawn to possible regulatory properties of selected sequences of matrix chondroitinsulfate, as far as chondroprotection is concerned. PMID- 7995677 TI - Role of the oligosaccharide inner core in the inhibition of human leukocyte elastase by chondroitin sulfates. AB - A chondroitin 4-sulfate and 6-sulfate mixture (CS) extracted from selachian cartilage and a purified preparation of the above glycosaminoglycans from bovine trachea, have been comparatively assayed with respect to the kinetics of human elastase activity. The selachian extract CS, but not the bovine one, inhibited the hydrolysis of N-tert-butyloxycarbonyl p-nitrophenyl ester in vitro (ki = 4.0 micrograms/ml). By fractioning both extracts on Sephadex, the inhibition was found to be related to the presence of a 40-50 KD peak (ki = 2.3 micrograms/ml). This particular fraction was present in the selachian extract CS from matrix, being absent from the bovine trachea extract CS (70% CSC) from Sigma. It showed a single Coomassie- and PAS-stained band approximately 47 kDa in m.w. on sodium dodecylsulfate polyacrylamide gel electrophoresis. Cleavage of the O-glycoside link by alkali hydrolysis of the eluted band, did not influence the enzyme inhibition (ki = 2.1 micrograms/ml). At variance, extensive hydrolysis of ester linkages by fluoride ion resulted in the lowering of inhibition (ki = 5.8 micrograms/ml). Apparently, the preservation of the trisaccharide region in the carbohydrate residues of proteoglycan is mandatory for the inhibition of elastase by low-sulfated chondroitinsulfates. PMID- 7995678 TI - Structure of low-molecular-weight chondroitinsulfate. AB - The structure of low-molecular-weight chondroitinsulfate (LMW-ChS, principal component of Matrix) was elucidated by a combination of physico-chemical and enzymatic methods. High-field 1H- and 13C-NMR spectra provide a characteristic fingerprint of this glycosaminoglycan. From the relative intensity of typical signals, the distribution of the sulfate group of LMW-ChS was shown to be 75.5% on O-6, and 27.5% on O-4 of the galactosamine unit. Together with the HPLC profiles, the 13C-NMR spectra also allowed, from the intensity of typical signals of end-residues, the determination of the average molecular weight and the molecular-weight distribution of LMW-ChS. This structural analysis is consistent with results obtained by enzymatic degradation with chondroitinases and analysis (by chromatography and NMR) of fragments. PMID- 7995679 TI - Metabolic fate of partially depolymerized shark chondroitin sulfate in man. AB - Chondroitin sulfates and other glycosaminoglycans are administered as drugs to man by intravenous, intramuscular or oral routes. There are some studies on the pharmacokinetics of heparin, heparan sulfate and dermatan sulfate, whereas few data are available on the metabolic fate of chondroitin sulfate in man. Partially depolymerized chondroitin sulfate (mean mol. wt: 7.5 kd, range 5-10 kd) with a ratio of 1:3 between chondroitin-4-sulfate and chondroitin-6-sulfate has been administered as single administrations of 0.2 and 1.2 g by intramuscular and oral routes respectively to 10 healthy volunteers (5 males and 5 females), aging 25-53 years. After intramuscular administration the plasma level increased to a concentration peak at 90 min. The peak concentration, the elimination half-life and the apparent distribution volume were respectively 3.8 mcg/ml, 275 min and 0.40 ml/g. About 37% of the administered chondroitin sulfate is excreted in the urine during the first 24 h as high- and low-molecular-weight derivatives. After oral administration the concentration peak was observed at 240 min. The concentration at the peak, the elimination half-life and the apparent distribution volume were respectively 4.6 mcg/ml, 310 min and 0.44 ml/g. A peak of mono-, oligo- and polysaccharides with a molecular weight lower than 5 kd derived from partial digestion of exogenous chondroitin sulfate is also present in plasma. This study shows that about 10% and 20% of the orally administered drug is absorbed as high- and low-molecular-weight derivatives respectively. Comparison with the results obtained in experimental animals indicate that the metabolic fate of partially depolymerized chondroitin sulfate is similar in man and in experimental animals. PMID- 7995680 TI - Articular cartilage echography as a criterion of the evolution of osteoarthritis of the knee. AB - We propose a modification of the Aisen's technique by which precise reproducible measurements of articular cartilage thickness of the knee is possible. A group of 23 patients with severe osteoarthritis was studied by ultra-sound (US) before knee prosthesis surgery. Evaluation with US was performed by a real-time scanner with a 7.5 MHz linear probe with upper-patellar transverse scans tangent to the upper patellar pole at 90 degrees knee flexion. The cartilage thickness was measured within the weight-bearing area. After surgery, on the corresponding gross pathological specimen, US re-evaluation and histological measurements were made. Results of pre- and post-operative ultrasonography (US) data were compared with histological data and a good correlation between these measurements was found (p(t) > 10%). Preoperative measurements ranged from 2.4 to 0.3 mm. In order to obtain normal reference values of the articular cartilage within the weight bearing area of the femoral trochlea for comparison, a group of 10 control subjects was also studied with US as above. The US data were then compared with computed tomography (arthro-CT) evaluations. No significant differences in mean values were found between the two imaging techniques (2.2 mm versus 2.3 mm for the lateral condyle and 2.3 versus 2.3 for the medial condyle, respectively). We conclude that ultra-sound measurement of articular cartilage thickness of femoral condyles is a sensitive and reproducible technique which permits early diagnosis and management of knee arthropathy and also quantification of cartilage damage. PMID- 7995681 TI - New joint imaging tools in osteoarthritis. I--Validation and preliminary experience with GGGS treatment. AB - In the pathology of joints, the main aim is an early diagnosis. In osteoarthritis (OA), where laboratory support is particularly poor, traditional radiology is informative only when the pathologic process is so advanced that prevention is difficult, either by changing life habits or by treating with chondroprotective drugs. Therefore an ideal diagnostic imaging tool should be sensitive, specific, reproducible and not invasive. In our opinion, Nuclear Magnetic Resonance (NMR) has all these characteristics and in particular can show meaningful pictures of cartilage and subchondral bone. We therefore compared NMR and traditional radiology to the gross pathology shown by arthroscopy at an early stage of OA, before and after treatment with glycosamino-glucuron-glycan-sulphate (GGGS) or placebo. Our results suggest that NMR is quite meaningful and can detect early OA joint modifications. With this technique the placebo-treated OA patients showed a natural increase in their pathologic picture, while the GGGS-treated patients seemed to experience a retardation in the progression of the disease. PMID- 7995682 TI - Efficacy and tolerability of galactosamino-glycuronoglycan-sulfate in osteoarthritis of the knee: an 11-month experience. AB - Chondroprotective agents represent a model for basic therapy of osteoarthritis (OA), thanks to their activity directed towards the protection and repair of articular cartilage. One of the most recent compounds capable of interfering with the pathogenic mechanisms of OA is galactosamino-glycuronoglycan-sulfate (GGGS), a highly depolymerized glycosaminoglycan with favourable chondroprotective and anti-inflammatory properties. The present paper describes the experience with GGGS given to a group of patients with symptomatic OA of the knee as compared to a parallel group treated with placebo. The drug (or placebo) was administered in two series of 25 intramuscular injections each over a period of 11 months, and four successive evaluations of treatment were made at various times during this period, and a fifth evaluation one month after the suspension of treatment to better evaluate the permanence of the therapeutic effect. The results obtained showed significant improvements on pain, algofunctional index and consumption of NSAIDs only in the group treated with GGGS. The drug was well tolerated and no reduction of dosage or drop-out from therapy were required. The favourable clinical effects and the patients' good compliance make GGGS a useful drug for successful chondroprotective treatment of OA. PMID- 7995683 TI - The development of dual relationships: power and professional responsibility. PMID- 7995684 TI - The US Supreme Court looks at voluntariness and consent. PMID- 7995685 TI - Violence and paranoid schizophrenia. PMID- 7995686 TI - Behavioral and affective correlates of Borderline Personality Organization in wife assaulters. PMID- 7995687 TI - Follow-up of 91 mentally ill criminals discharged from the maximum security hospital in Barcelona P.G. PMID- 7995689 TI - Fitness to stand trial in Canada in light of the recent Criminal Code amendments. PMID- 7995688 TI - Suggestions for the clinical and forensic use of the Hare Psychopathy Checklist Revised (PCL-R). PMID- 7995690 TI - Mental health and minority religions: the latest weapon in custody battles. PMID- 7995691 TI - Qualitative and quantitative comparative study on different filling materials used in bone tissue regeneration: a controlled clinical study. AB - This study compared, in a human model, the ability of (1) expanded polytetrafluorethylene (e-PTFE) membranes plus bone-chip autografts, (2) e-PTFE membranes plus demineralized freeze-dried bone, (3) e-PTFE membranes plus a new form of demineralized allograft bone tissue, and (4) e-PTFE membranes alone to enhance bone regeneration around dental implants placed into recent extraction sockets. The histologic results demonstrated that, in humans, guided tissue regeneration techniques are capable of producing new bone osseointegrated with titanium dental implants. Among the graft materials, autogenous bone provided the densest and the greatest amount of bone formation, but use of demineralized freeze-dried bone and a new form of de-mineralized allogenic bone matrix also improved bone regeneration compared to membranes alone after 6 months of healing. PMID- 7995692 TI - Use of the supraperiosteal envelope in soft tissue grafting for root coverage. I. Rationale and technique. AB - Recent advances in graft procurement and suturing encourage a reassessment of the "envelope" technique in soft tissue grafting for root coverage. Use of the supraperiosteal envelope permits conservation of existing gingiva, minimal surgical trauma to the recipient area, and firm fixation of the connective tissue graft over single and multiple adjacent areas of recession. The intimate coaptation of the bilaminar soft tissue complex thus achieved may facilitate graft survival and postoperative blending of soft tissues. PMID- 7995693 TI - The coronally positioned pedicle graft with inlaid margins: a predictable method of obtaining root coverage of shallow defects. AB - There are several techniques that will predictably cover exposed root surfaces; however, most techniques are generally used to treat larger recession areas or sites with inadequate keratinized tissue. The purpose of this study is to evaluate the use of the coronally positioned pedicle graft with inlaid margins in the treatment of shallow recession areas. Utilizing the described technique, 20 isolated Class I defects were treated. Complete root coverage was obtained 95% of the time; the mean root coverage was 98.8%. The procedure resulted in a decrease in sensitivity, the final color and tissue contours of the grafts were excellent, and all patients were satisfied with the results. The coronally positioned pedicle graft with inlaid margins is a simple and predictable method to cover exposed root surfaces in shallow recession areas. PMID- 7995694 TI - Guided tissue regeneration around dental implants in immediate extraction sockets: comparison of e-PTFE and a new titanium membrane. AB - To evaluate the efficacy of guided tissue regeneration around exposed implant threads, 16 implants were placed into fresh extraction sockets in beagle dogs. Polytetrafluoroethylene (e-PTFE) membranes and titanium membranes were used to cover the defects around implants. A control group did not receive any membranes. Results were evaluated histologically. The average gain in bone height was 2.1 mm for e-PTFE sites, 0.8 mm for titanium membranes, and 2.9 mm for control sites. The greatest gain in bone levels was seen for two sites that received e-PTFE membranes and remained covered for the entire evaluation interval. Within the limits of this study, clinical and histologic evidence demonstrated that, when primary coverage is maintained, the use of e-PTFE membranes can significantly enhance bone regeneration around implants. PMID- 7995695 TI - Clinical evaluation of guided tissue regeneration in the treatment of grade II molar furcation invasions. AB - This paper evaluates the use of guided tissue regeneration for treating 19 pairs of molar grade II furcation defects. Presurgical measurements were taken for the determination of aveolar crestal resorption, vertical open probing attachment, and horizontal open probing attachment. The surgical procedure consisted of sulcular incision, full-thickness facial and lingual flaps, soft tissue debridement, and root planing. One defect from each pair of furcas was treated with an expanded polytetrafluoroethylene membrane, which was left in place for 4 to 6 weeks. Postsurgery soft tissue measurements showed a reduction in probing depth and a gain in vertical and horizontal open probing attachment. PMID- 7995696 TI - Marginal adaptation of crowns: a scanning electron microscopic investigation. AB - Most studies on marginal adaptation have been performed in vitro; only a few studies have investigated in vivo marginal adaptation and microleakage of crowns. In this study, gold crowns were prepared and cemented on abutments, and their marginal discrepancies were analyzed by scanning electron microscopy according to the impression-replica and cross-section methods. Three observers measured the marginal discrepancies of each crown. Interobserver variance of accuracy was 10 microns by the impression-replica and 15 microns by the cross-section method. The mean values were 124.16 microns by the impression-replica and 129.79 microns by the cross-section method. The two methods tested showed similar results. PMID- 7995697 TI - Comparison between fast spin-echo and conventional spin-echo imaging of normal and abnormal musculoskeletal structures in children and young adults. AB - RATIONALE AND OBJECTIVES: The differences in imaging characteristics between conventional and fast spin-echo studies of the skeletons of children and young adults were evaluated. METHODS: Concurrent conventional and fast spin-echo studies of 23 patients were compared by measuring signal intensity, contrast, and, subjectively, conspicuity of normal and abnormal musculoskeletal structures. RESULTS: Fast proton-density-weighted images had lower signal-to-noise ratios of muscle, fat, and physeal, epiphyseal, and articular cartilage. Using more than three echoes for proton-density images resulted in blurring and decreased lesion conspicuity. On fast T2-weighted images, there was greater conspicuity of normal cortex, ligaments, and muscle; but less contrast between fat and water because of a higher signal-to-noise ratio of fat. When both sequences were obtained with similar image quality, fast spin-echo was 40% faster. CONCLUSION: Fast spin-echo studies allows faster imaging, but can have blurring on proton-density-weighted images and decreased fat-water contrast on T2-weighted images. PMID- 7995699 TI - In vitro metal fatigue testing of inferior vena cava filters. AB - RATIONALE AND OBJECTIVES: Inferior vena cava filter fractures have been described in vivo on several occasions. No studies have compared the fatigue life of the different filter types. Four different, frequently used filters (Vena-Tech filters [VTF], stainless-steel Greenfield filters [SSGF], Simon nitinol filters [SNF], and titanium Greenfield filters [TGF]) were, therefore, tested with regard to fatigue life. METHODS: Ten filters of each type were tested by compressing the filter legs repeatedly. A travel distance of 1.5 cm was used, setting minimal and maximal filter leg separations of 1.0 cm and 2.5 cm, respectively. The endpoint was filter fracture or 10,000,000 compressions. The test was then repeated on five of the filters from each group, but on a different filter leg pair. RESULTS: Seven of 10 VTFs fractured during the first part of the study, and all five VTFs fractured during the second part of the study. One SSGF fractured in each part of the study. None of the SNFs or the TGFs fractured. Significant difference in fracture frequency was found. CONCLUSION: The VTFs appear to have the shortest fatigue life. The TGF and the SNF have a fatigue life exceeding the test limits. The consequences of filter fracture are unknown. PMID- 7995698 TI - Association between anthropometric measures and spinal bone mineral density. AB - RATIONALE AND OBJECTIVES: The relationship of vertebral bone mineral density (BMD) to various anthropometric factors, including body weight and height, vertebral volume, and muscle area was examined. The sex- and menopause-related differences in these relationships also were studied. METHODS: Both cortical and trabecular BMD were measured using quantitative computed tomography (QCT). Integral BMD was measured using dual x-ray absorptiometry (DXA) in 74 men and in 96 premenopausal and 155 postmenopausal women. The psoas muscle area was measured using CT images. Vertebral volume was determined using CT images and CT topography. RESULTS: Bone mineral density had the strongest relationship with age in postmenopausal women. Trabecular BMD was correlated with muscle area and vertebral volume in premenopausal women, but not in postmenopausal women. The correlation of trabecular BMD with various anthropometric factors in men was stronger than that in women. Dual x-ray absorptiometry-BMD was found to be more affected by bone volume than was QCT-BMD. CONCLUSIONS: The association of anthropometric factors with BMD differs in men and women, as well as in premenopausal and postmenopausal women. PMID- 7995700 TI - Magnetic resonance microscopy of the rat carotid artery at 300 megahertz. AB - RATIONALE AND OBJECTIVES: Magnetic resonance microscopy (MRM) has evolved from a technical curiosity to a tool with which researchers can study important disease models. But MRM is not simply an extension of clinical magnetic resonance imaging. In this article, the unique adaptations of MRM required in the study of carotid artery disease are outlined. The techniques of MRM are integrated into a specific model of carotid artery disease in the rat to allow in vivo studies of vascular wall thickening after removal of the vascular endothelium. METHODS: Imaging was performed at 300 MHz in 250-gm Sprague-Dawley rats using surgically implanted radiofrequency coils to localize the region of interest and to provide an increase in the signal-to-noise ratio over that of volume or surface coils. A three-dimensional Fourier encoding sequence was modified with flow-dephasing gradients to minimize signal and artifacts from moving blood. RESULTS: In vivo images were acquired with spatial resolution of 25 x 25 x 400 microns and signal to-noise ratio more than sufficient to define the morphology of the vascular wall. Significant changes in the intensity and distribution of signal were visible in the area surrounding the vessel after angioplasty. CONCLUSIONS: Signal to-noise improvements from surgically implanted coils coupled to a three dimensional radiofrequency-refocused sequence with flow-dephasing gradients were sufficient to define the wall of the carotid artery. The diffusion-weighted pulse sequence detects signal changes in the area surrounding the vessel after angioplasty. The MRM techniques described and the contrast observed allow us, for the first time to follow in vivo the early stage of developing atherosclerosis in the vessel wall and closely surrounding tissue. PMID- 7995701 TI - Prediction of change in mitral valve area after mitral balloon commissurotomy using cine computed tomography. AB - RATIONALE AND OBJECTIVES: Mitral balloon commissurotomy (MBC) can successfully increase the mitral valve area (MVA) in mitral stenosis, but the outcome is variable. In multicenter studies, qualitative echocardiographic scores obtained before MBC are only weakly predictive of the increase in MVA after MBC. METHODS: To evaluate whether the change in MVA after MBC can be predicted by evaluating mitral valve morphology using cine computed tomography (CT), we studied 12 women with mitral stenosis and 11 female control subjects. RESULTS: In the patients with mitral stenosis, MVA increased from 1.13 +/- 0.24 to 1.93 +/- 0.56 cm2 (P < .0001) after MBC. A standard echocardiographic score assessment of mitral valve morphology before MBC was not associated with the change in MVA after MBC in these patients (P > .20). However, the total mitral valve morphology score evaluated by cine computed tomography was strongly associated with the change in MVA after MBC (r = -.87; P < .0005). In addition, the individual morphologic characteristics of mitral valve mobility (P < .0025), leaflet thickness (P < .05), and subvalvular disease (P < .05) were significant predictors of the change in MVA after MBC. CONCLUSION: Cine computed tomography may be useful for predicting immediate increases in MVA in patients after MBC and may be helpful for preoperative assessment of these patients. PMID- 7995702 TI - Monitoring substrate uptake and distribution by tumors using percutaneous catheters and solid nuclear track detectors. AB - RATIONALE AND OBJECTIVES: This study was designed to test a new technique for measuring intratumoral drug and substrate concentrations using a modified percutaneous catheter and solid nuclear track detectors. MATERIAL AND METHODS: A nephrostomy catheter was modified to allow exposure of the lumen of the catheter to adjacent tissue and placed percutaneously in a 4047 colon cancer growing in the flank of a Fischer 344 rat. Measurement of metabolite distribution was obtained using carbon-14-labeled deoxy-d-glucose and multiple strips of CR-39 (a solid nuclear track detector) placed sequentially in the catheter to measure the low energy beta emissions from the carbon-14. RESULTS: The administered deoxy-d glucose initially distributed to the vascularized rim of the tumor, but rapidly defused down concentration gradients into the necrotic core. CONCLUSION: The preliminary data suggest that this technique is feasible. Further validation studies may show that this technique may allow for monitoring of temporal and spatial variations in the distribution of drugs and metabolites within tumors. PMID- 7995705 TI - Breath-holding capability of adults. Implications for spiral computed tomography, fast-acquisition magnetic resonance imaging, and angiography. AB - PURPOSE: The breath-holding capabilities of various groups of individuals were evaluated to develop protocols so that patients undergoing spiral computed tomography (CT), digital angiography, and breath-hold magnetic resonance imaging (MRI) can be studied successfully. METHODS: Twenty-five outpatients and 25 inpatients (all adults) were studied before undergoing body CT. Each subject was asked to hold his or her breath for as long as possible. Then each patient was asked to perform as many repetitive 12-second breath holds as possible. These data were correlated with demographic and historical information. RESULTS: The maximum breath-hold time for inpatients and those outpatients who were heavy smokers or had chronic obstructive pulmonary disease (COPD) or congestive heart failure (CHF) was 18 to 32 seconds (95% confidence interval) with a mean of 25 seconds. For all other outpatients, breath-hold time was 38 to 56 seconds (mean = 45 seconds). The 95% confidence interval for the number of 12-second breath holds for these two groups was 4 to 6 breath holds (mean = 4.9) and 6 to 7 breath holds (mean = 6.6), respectively. One inpatient could not hold his breath at all and three others were only able to hold their breath once for short periods. The sex and age of the patient had no significant effect on breath-holding performance. CONCLUSIONS: Breath-holding protocols must account for the diminished capabilities of most inpatients, and outpatients who are heavy smokers or have COPD or CHF. Most outpatients who are not heavy smokers or without COPD or CHF can achieve a single breath hold of 38 seconds, or up to six 12-second breath holds. PMID- 7995704 TI - Evaluation of a combined two- and three-dimensional compression method using human visual characteristics to yield high-quality 10:1 compression of cranial computed tomography scans. AB - RATIONALE AND OBJECTIVES: The compression of cranial computed tomography scans was improved by using independent intra- and interframe compression techniques. METHODS: For intraframe compression, an image was decomposed into four subimages, one subimage was chosen as a reference subimage, and three of the subimages were predicted from the reference subimage. The prediction error was encoded with a classified vector quantizer (CVQ) based on human visual perception characteristics. Interframe redundancy is exploited by a displacement estimated interslice (DEI) algorithm that encodes the differences between reference subimages from adjacent slices. This combined DEI/CVQ method was subjectively evaluated by 13 radiologists under a blinded protocol, and was compared to the CVQ method alone, the DEI method alone, the original images, and to a standard intraframe discrete cosine transform (DCT) compression method. RESULTS: Only the combined DEI/CVQ method at 10:1 compression was not scored significantly different from the original images. At 15:1 compression, the DEI/CVQ method was scored significantly better than the 10:1 DCT and any other 15:1 compression methods. CONCLUSIONS: Compressed image quality is enhanced by exploiting inter- and intraframe redundancy, and by modeling some characteristics of human visual perception. The DEI/CVQ method is well-suited for progressive transmission, and thus, holds potential in teleradiology as well as picture archiving and communications systems. PMID- 7995703 TI - Transthoracic percutaneous ethanol injection into the liver. AB - RATIONALE AND OBJECTIVES: The feasibility of the new transthoracic approach of percutaneous ethanol injection through the lower lung to the subphrenic region of the liver was evaluated in normal rats. METHODS: Fourteen normal rats received percutaneous ethanol injection. A 22-gauge fine needle was inserted into the liver via the thoracic cage and through the lower lung parenchyma under computed tomographic (CT) guidance. After ethanol (0.1-0.2 mL) was injected, three follow up CT scans were performed: immediately after, 1 day after, and 1 week after the initial injection. All animals were killed 1 week after injection to evaluate macroscopic changes of the diaphragm and pleura. RESULTS: No major complications were observed. Minor complications were observed in six rats; these included one pneumothorax (7%) and five band-like and streaky shadows (presumably pulmonary hemorrhages) (35%) on the CT scan obtained immediately after the procedure. However, all complications had disappeared spontaneously in the follow-up CT scan obtained 1 day after the procedure. At autopsy, no pleural changes were seen. CONCLUSIONS: This study demonstrates that percutaneous ethanol injection through the lower lung parenchyma is achievable. Although this study was performed only in normal rats, the transthoracic approach can be a complementary method of ultrasound-guided percutaneous ethanol injection for tumors in the subphrenic region of the liver. Further study will be needed in abnormal livers and then in human subjects to verify the safety and efficacy of this procedure. PMID- 7995706 TI - Scatter-reduction characteristics of an infinity-focused gridded radiographic cassette. AB - RATIONALE AND OBJECTIVES: The scatter-reduction properties of a new infinity focused grid incorporated into a radiographic imaging cassette were analyzed. METHODS: A polystyrene chest phantom was imaged using the cassette and bedside radiographic procedure. Scatter fractions were measured using a beam-stop technique at several anatomically equivalent locations. The performance of this cassette also was evaluated as a function of the orientation angle. RESULTS: The gridded cassette provided a decrease in scatter fraction from 61% to 49% in the lung and from 87% to 76% in the mediastinum. To obtain equivalent film density when the grid was used, the exposure was increased by a factor of 3.0. While there was a decrease in scatter clean-up as the film cassette was tilted from the perpendicular, the grid performed well out to an angle of 10 degrees. CONCLUSION: The gridded cassette for portable radiography provides scatter reduction with little sensitivity to alignment. The availability of this device could improve scatter rejection, and therefore, contrast in portable radiographic imaging. PMID- 7995707 TI - Calculating the costs of undergraduate medical education in radiology. AB - RATIONALE AND OBJECTIVES: The current stringent financial constraints mandate that radiology departments carefully assess the costs involved in undergraduate medical education. We performed a cost-accounting analysis of the radiology department's participation in an introductory clinical medicine course, which could serve as a methodologic model for realistic cost assessment of any new or existing course. MATERIALS AND METHODS: Each day of the 5-week radiology portion of the second-year course consists of 1 hour of lecture and 5 hours of small group discussions regarding chest, abdominal, and skeletal radiology; neuroradiology; and nuclear medicine. Marginal cost is defined as the additional real cost involved in creating or conducting a course. Opportunity costs represent alternative use of instructional resources. RESULTS: The marginal cost (additional real cost) of providing the course for the first time was $37,475. Subsequent offerings of the course will cost approximately $24,375. CONCLUSION: Resources expended for any instructional purpose must be weighed in terms of marginal and opportunity costs. It is mandatory that adequate cost analysis for undergraduate education in radiology be developed so that sound choices can be made regarding resource consumption. PMID- 7995708 TI - An audit of clinico-radiologic conferences. AB - RATIONALE AND OBJECTIVES: To assess the various functions of regular review conferences between clinicians and radiologists, proceedings at 19 such meetings were audited. In particular, the authors attempted to quantify their educational component. METHODS: The cases discussed during each meeting were monitored, and the educational component was assessed. Changes in imaging strategy, diagnosis, and management were noted. The participants were questioned regarding their perceptions of such meetings. RESULTS: Two hundred cases were presented at 19 meetings (mean duration 44.8 minutes). Overall, 75 of the 200 cases (37.5%) were presented for routine purposes, 100 (50%) for radiologic assistance, and 25 (12.5%) for general interest. More changes in diagnosis and management and a greater educational contribution occurred in those cases presented for radiologic assistance than in those presented out of routine. Most participants considered that these meetings bestowed considerable benefit to their continuing medical education and to the management of their patients. Discussion considered of educational value developed in 88 of the 200 patients presented; this discussion required 61.7% of the total duration of these meetings. CONCLUSIONS: These conferences provide benefit to the patient, as well as serving an educational role for the medical community. Discussion of imaging strategies and the presentation of controversial and interesting cases should be particularly encouraged. PMID- 7995710 TI - It didn't do me any harm. PMID- 7995709 TI - Research impact assessment. Principles and applications to proposed, ongoing, and completed projects. AB - Three generic types of RIA approaches used by the federal government were described (retrospective, peer review, and quantitative methods). Peer review is the method used most frequently. All methods examined have their unique shortcomings. A fundamental problem is that many research impact targets exist. These include impacts on the research field itself, allied research fields, technology, systems, operations, education, etc. The strength of the specific impact of the research on each of these targets and the weighting assigned to the value of the research impact on each of these targets depends on the technical, organizational, and personal perspectives of the reviewers. Much of the research evaluation community has come to believe that simultaneous use of many techniques is the preferred approach. However, there is little evidence of multiple technique use by the federal government in impact assessment, especially bibliometrics to support peer review. This area is ripe for exploitation. PMID- 7995711 TI - Over-worked and under-valued. PMID- 7995712 TI - Jam today for our junior people. Interview by Alison Whyte. PMID- 7995713 TI - Back to the workhouse. PMID- 7995714 TI - A case for civil disobedience. AB - As a practising health visitor, Lindis Percy believes her involvement in non violent direct action against military weapons, and against nuclear warfare in particular, is integral to both her personal and professional philosophies. Here she describes her involvement in the Greenham Common and Menwith Hill protests, and subsequent court victories. PMID- 7995715 TI - Measure for measure. PMID- 7995716 TI - Preventing SIDS. Evidence of health visitors changing their practice. PMID- 7995717 TI - Achieving quality standards in health visiting. AB - Standard-setting and audit should be integral to health visiting practice, to enable purchasers, provider units and field staff to ensure quality of services to clients. Theresa Chakravorty describes a simple audit process piloted in South Glamorgan, which focused on implementation of the universal primary birth home visit programme. PMID- 7995718 TI - Developing a computerised caseload database. AB - Health visitors are employed to promote actively the health of the community. This role frequently involves visits to clients, to assess their individual health needs and to promote good health practice. Angela Pogmore describes how caseload data within what is now the Central Nottinghamshire Healthcare (NHS) Trust was placed on a computer database as an alternative to the existing paper system, in order to develop a tool for health visitors rapidly to identify at risk groups and optimise the use of existing resources through improved targeting. PMID- 7995720 TI - Clients' views of a health visiting service. AB - A consumer survey carried out by health visitors in north east, Fife, revealed overwhelming satisfaction with the current service. However some parents wanted more group work, to tackle specific child health issues. Marianne Cowpe et al describe the results of the survey, and the developments they now plan to make in the range of services provided. PMID- 7995719 TI - Clinical audit of health visitor interventions in child accident prevention. AB - The Health of the Nation strategy has set a target for reducing the death rate from accidents among children aged under 15 by at least 33 per cent by 2005. Accidents are included because they present a major health issue. Maureen Carson and Rosemary Thompson describe the part played by health visitors in the Norwich Community Health Services strategy to cut child accident rates, and the important role of the hospital paediatric liaison health visitor. PMID- 7995721 TI - Developmental supervision in health visiting. AB - Although supervision is supposed to be a helpful and supportive process, it is often seen as negative and critical. Meg Bond and Stevie Holland describe a developmental model of supervision, which can enhance health visitors' personal and professional development. PMID- 7995723 TI - Fit for 2000: cutting child accidents in Peacehaven. PMID- 7995722 TI - Selling the safe sun message. PMID- 7995724 TI - Long distance dinner. PMID- 7995725 TI - Pay more, get less: a new definition of incapacity. PMID- 7995726 TI - Immunisation. At the sharp end. PMID- 7995727 TI - Record and survive. PMID- 7995728 TI - Re-usable alternatives. PMID- 7995729 TI - Skill mix compromises standards. PMID- 7995730 TI - Electron micrograph map of the Drosophila melanogaster polytene chromosome 3R divisions 81 through 90. AB - The banding pattern of the proximal half of the polytene salivary gland 3R chromosome of Drosophila melanogaster was studied with thin section electron microscopy. Bands were identified according to Bridges' revised light microscopic map, which contains 330 single and 121 double bands within the regions 81 through 90. We found a total of 447 bands in this region. 97 Bridges' single bands were easily detected in almost all thin sections, while 177 faint bands could be seen only in some micrographs. 56 Bridges' single bands could not be found. 32 Bridges' doublets were made up of two separate bands each in thin sections. The other 89 Bridges' doublets seemed to be either single bands or remained obscure. A total of 20 small new bands, which were not drawn on Bridges' map, were detected. PMID- 7995732 TI - Distribution of P and hobo mobile elements in environmentally manipulated long term Drosophila melanogaster cage populations. AB - The copy number and the chromosome positions of the P and hobo insertions were determined by means of in situ hybridization to polytene chromosomes, in five long-term Drosophila melanogaster cage populations kept for 18 years under different culture conditions (temperature and relative humidity). The analysis revealed that the copy number of both P and hobo elements were similar between the populations kept under the same culture conditions and significantly different among the populations maintained under different culture conditions. A tendency for similar distribution of these elements along the major chromosome arms was also observed in the populations of the same environmental manipulation. The distribution of the insertions along the chromosomes was not random for both the P and hobo elements; sites with high insertion frequencies were found (hot spots of occupation). Some of them were common in all cage populations while others were characteristic of the populations kept under the same conditions. Finally, fixed sites of occupation were also observed in all populations and refer mostly to hobo distribution. The data are discussed on the basis of the possible involvement of the P and hobo elements, in some way, to the adaptation process and speciation. PMID- 7995731 TI - Chromosome studies of H9/HTLV III B cells and blood lymphocytes infected with human immunodeficiency virus (HIV-1). PMID- 7995733 TI - Family physicians key partners in preventing suicide among youth. PMID- 7995734 TI - NSAIDs questionable as first-line therapy for rheumatic conditions in the elderly. PMID- 7995735 TI - The osteopathic medicine game: new strategies for winning. AB - The recruitment and retention of osteopathic medical students by osteopathic medical institutions is arguably the most important priority facing the profession today. Residencies accredited by the Accreditation Council on Graduate Medical Education are now the major competitors for osteopathic medical students; osteopathic residency graduates are readily accepted at most hospitals; and osteopathic medical faculty are regularly appointed to university and government positions. As a result, many osteopathic medical institutions are having difficulty in filling their training programs and recruiting faculty and medical staff physicians. These recruitment problems can be resolved by the development of graduate medical education (GME) programs that are competitive with their allopathic GME counterparts, but hospitals and colleges must do so by developing a new approach to osteopathic GME. Osteopathic GME must sell academic quality by developing a university-like environment in the hospitals conducting training programs. Osteopathic training hospitals should consider requiring their directors of medical education to develop strategic plans for GME which result in the development of competitive programs. PMID- 7995736 TI - Clinical practice guidelines: a review. AB - The development of clinical practice guidelines has spread from utilization review agencies to physician specialty societies, federal agencies, managed care organizations, and academic health centers as their usefulness in accomplishing the goals of healthcare reform become clear. The author reviews the mounting evidence that variation in the practice of medicine suggests that patients in some areas are not receiving all needed services, while others are receiving unnecessary services. He explores the implications of practice guidelines for improving the quality of care while controlling cost. Practice guidelines are defined and distinguished from medical review criteria. The author explores the challenges in governance, funding, and guideline development and communication that will have to be overcome to establish the credibility of practice guidelines. Finally, he addresses the opportunities for the osteopathic medical profession to establish its uniqueness in this setting. PMID- 7995737 TI - Automotive airbag-induced second-degree chemical burn resulting in Staphylococcus aureus infection. AB - A young woman did not seek emergency treatment after a minor automobile collision as she thought that she had been spared serious injury by the inflation of the driver's-side airbag. She had a benign-looking erythema on her neck which, over the next several days, became a second-degree chemical burn infected with Staphylococcus aureus. The burn and subsequent infection took several weeks to heal and the patient had to endure a prolonged course of antibiotics, nonsteroidal antiinflammatory drugs, and continued irrigation. This case exemplifies why alkali chemical burns from an automotive airbag should be treated aggressively, despite their benign appearance, as they may take several days to evolve. Physicians should be warned that careful follow-up examination of patients seen in the hospital emergency department or in the physician's office is necessary to abate any hidden sequelae. Of course, the opportunity to decrease morbidity is lost if the patient does not seek emergency treatment. PMID- 7995738 TI - A variant of adrenomyeloneuropathy in a family with adrenoleukodystrophy and adrenomyeloneuropathy. AB - A 31-year-old man was seen with addisonian crisis, followed by the abrupt onset of spastic paraparesis and peripheral neuropathy. A workup revealed adrenal insufficiency, for which the patient was aggressively treated. The workup also revealed an increase in very-long-chain fatty acids consistent with the diagnosis of adrenomyeloneuropathy. Abnormal pituitary dysfunction improved with treatment of the Addison's disease. A review of the patient's pedigree revealed two family members in whom multiple sclerosis had been diagnosed but which, in retrospect, was thought to be adrenomyeloneuropathy. No other family member was found to have Addison's disease. A sibling died at age 8 of Schilder's disease, confirming the presence of adrenoleukodystrophy as well as adrenomyeloneuropathy within this family. PMID- 7995739 TI - Survey of brachytherapy practice in the United States: a report of the Clinical Research Committee of the American Endocurietherapy Society. AB - PURPOSE: To obtain reliable data on the extent of the brachytherapy practice in the United States by conducting a comprehensive survey of all facilities. METHODS AND MATERIALS: The Clinical Research Committee of the AES surveyed all 1321 radiation oncology facilities identified in the Patterns of Care Study (PCS) of the American College of Radiology (ACR). Multiple mailings and follow-up were made to obtain a high response rate. Survey responders and nonresponders were compared using chi-square tests. Summary statistics were reported. RESULTS: Of the 1321 facilities, 1054 responded (80%). Hospital-based and larger facilities had a statistically significant higher rate of response. Brachytherapy was being performed at 819 facilities (the median number of procedures = 21-50). Two hundred and two facilities did no brachytherapy. The common isotopes used were 137Cs (705 facilities), 192Ir (585 facilities), 125I (236 facilities), and 131I (194 facilities). The common brachytherapy techniques used were intracavitary (751 facilities), interstitial (536 facilities), intraluminal (310 facilities), and plaques (148 facilities). Remote afterloaded brachytherapy was used at 205 centers as follows: high dose rate (HDR) (164), medium dose rate (MDR) (5), and low dose rate (LDR) (36). Computerized dosimetry was most commonly used (790 facilities), followed by Patterson-Parker (104 facilities) and Quimby (72 facilities). The common sites treated were cervix (701 facilities), endometrium (565 facilities), head and neck (354 facilities), and lung (344 facilities). CONCLUSION: Data regarding brachytherapy practice has been obtained from a large percentage (80%) of all facilities in the United States. The majority (78-81%) of radiation oncology facilities perform brachytherapy; however, its use is restricted to gynecological implants in many of these centers. The results from this survey will be used to develop a pattern of care study and data registry in brachytherapy. PMID- 7995740 TI - Conventional four-field pelvic radiotherapy technique without computed tomography treatment planning in cancer of the cervix: potential geographic miss and its impact on pelvic control. AB - PURPOSE: To evaluate the impact of inadequate margins on pelvic control using the conventional four-field pelvic portals without computed tomography (CT)-treatment planning. METHODS AND MATERIALS: Between 1986 and 1991, 34 patients with invasive cancer of the cervix were eligible for outcome study of conventional four-field radiation therapy (10 Stage I, 16 Stage II, 8 Stage III). The eligibility for this study includes four-field pelvic technique, definitive radiation therapy, and diagnostic CT scan of the pelvis. For this study, an inadequate margin is arbitrarily defined as < or = 1.0 cm of normal tissue around the CT-defined tumor volume. RESULTS: All 34 patients had adequate margins for anterio posterior/posterio-anterior portals. However, 19 patients had an inadequate margin at the posterior border (S2-S3 interspace) and/or custom-shaped rectal block for lateral pelvic portals. Two patients had inadequate margins at the anterior border (level of symphysis pubis) due to an enlarged uterus. With a median follow-up of 36 months, pelvic control for adequate margins and inadequate margins was 100% and 71% for Stage IB disease and 88% and 50% for Stage IIB disease, respectively. However, pelvic control for Stage IIIB disease was 50% for both groups. There was no difference in total dose to point A or point B between the two groups. CONCLUSION: Our preliminary data show higher local failure in patients with an inadequate margin. For four-field pelvic radiation therapy, we strongly recommend CT-treatment planning. Otherwise, anterio-posterior/posterio anterior pelvic therapy is the most reliable treatment for cancer of the uterine cervix. PMID- 7995741 TI - Measurement of prostate movement over the course of routine radiotherapy using implanted markers. AB - PURPOSE: To measure the range and frequency of occurrence of intertreatment movement of the prostate gland over the course of radiotherapy, and to demonstrate that the prostate may move independently of the surrounding bones of the pelvis. METHODS AND MATERIALS: Ten patients underwent implantation of radiopaque markers around the prostate. Orthogonal portal films were taken at multiple stages during the course of treatment and digitized. An image registration tool was used to solve for film detector placement and, subsequently, to determine positional changes between structures on a reference portal image pair and all subsequent pairs for each patient. Transformations describing prostate movement were measured independently of those describing setup variations of the pelvic girdle. RESULTS: Translation and/or rotation of the prostate was detected in 70% of the treatments for which films were taken. The maximum measured displacement was 7.5 mm along a major axis. Typical translations of the prostate were between 0-4 mm. The translation and rotation had a predominant direction, suggesting a natural axis for prostate movement. CONCLUSION: Although significant prostate displacement can occur between treatments, the typical range of movement seen along a major axis was less than 5 mm. Proper treatment planning should consider the movement of the target independent of surrounding bony anatomy. Advances in online portal imaging, image registration, and dynamic field shaping may permit shaped fields that encompass the prostate gland in its position at the time of treatment, allowing for the use of smaller fields while ensuring proper target coverage. PMID- 7995742 TI - Randomized comparison of cyclophosphamide-total body irradiation versus busulfan cyclophosphamide conditioning in autologous bone marrow transplantation for acute myeloid leukemia. AB - PURPOSE: This prospective trial of autologous bone marrow transplantation for acute myeloid leukemia was undertaken to compare the outcome using two different preparative regimens. METHODS AND MATERIALS: Between October 1987 and April 1993, 35 patients with acute myeloid leukemia in first (n = 12) or greater (n = 23) remission were stratified by remission status and randomized to undergo 4 hydroperoxycyclophosphamide purged autologous bone marrow transplantation after either cyclophosphamide (120 mg/kg) and total body irradiation (1320 Gy in eight fractions over 4 days) (CY/TBI), or busulfan (16 mg/kg) and cyclophosphamide (200 mg/kg) (BU/CY) conditioning. RESULTS: At 2 years, overall survival and disease free survival were 39% (95% confidence intervals (CI) 22-57%) and 36% (95% CI 19 52%), respectively. Patients in first complete remission had a significantly better outcome with a 2-year disease free survival of 57% (95% CI 28-86%) compared to others at 24% (95% CI 6-43%, log rank p = 0.048). For patients conditioned with CY/TBI, the estimated 2-year disease-free survival was 50% compared to 24% for patients conditioned with BU/CY (log rank p = 0.12). Estimated 2-year relapse rates were 43% vs. 70% (log rank p = 0.17), respectively. For patients in first complete remission no differences in disease free survival (2-year estimates 67% vs. 50%, log rank p = 0.69), between the two regimens were observed. For patients in greater than first complete remission there was a trend towards improved disease-free survival in the CY/TBI arm (2 year estimates 42% vs. 9%, log rank p = 0.06). There were no differences in time to white blood cell count (WBC) engraftment, absolute neutrophil count of > 500, incidence of bacteremias, or median time to hospital discharge between the two regimens. Acute toxicities were similar. Interstitial pneumonitis developed in two patients (one on each arm), while veno occlusive disease developed in three BU/CY patients, but none of the CY/TBI patients (log rank p = 0.07). CONCLUSIONS: Cyclophosphamide-total body irradiation provided an equivalent or better outcome to BU/CY, particularly in advanced patients, and should remain the standard by which new regimens are judged. The high relapse rate with both regimens, especially patients who were in greater than in first complete remission, emphasizes the need for early transplant and for new strategies to improve outcome. PMID- 7995743 TI - Management of retroperitoneal sarcomas: does dose escalation impact on locoregional control? AB - PURPOSE: Only 50% of patients with retroperitoneal sarcomas undergo complete resection and of these, 47% develop local tumor recurrence. To determine whether irradiation with dose escalation improves locoregional control, we reviewed the experience with adjuvant radiotherapy in the treatment of retroperitoneal sarcomas at the Fox Chase Cancer Center and the Hospital of the University of Pennsylvania. METHODS AND MATERIALS: Twenty-one patients with retroperitoneal sarcomas were treated with curative intent with surgical resection and radiation therapy at Fox Chase Cancer Center or the Hospital of the University of Pennsylvania between May 1965 and July 1992. Follow-up ranged from 14-340 months. Nineteen patients were treated postoperatively and 2 preoperatively. Radiation doses were between 36.0 Gy and 90.0 Gy (median 54.0 Gy). RESULTS: The 2-year rates of local control and survival were 72% and 69%, respectively. Tumor size, stage, grade, and histology did not influence local control. Two of eight patients (25%) who received a total dose of > 55.2 Gy experienced local failure compared to 5 of 13 (38%) who received < or = 55.2 Gy. One patient experienced a small bowel obstruction that required surgical intervention. There were no other severe complications. CONCLUSION: Postoperative treatment with radiotherapy using a dose > 55.0 Gy is recommended for patients with retroperitoneal sarcomas following surgical resection due to the significant likelihood of local recurrence. Innovative adjuvant radiation techniques to escalate doses to greater than 55.0 Gy including intraoperative radiation therapy, brachytherapy, or use of small bowel exclusion devices to reduce small bowel toxicity should be considered for retroperitoneal sarcomas. PMID- 7995744 TI - The Electronic View Box: a software tool for radiation therapy treatment verification. AB - PURPOSE: We have developed a software tool for interactively verifying treatment plan implementation. The Electronic View Box (EVB) tool copies the paradigm of current practice but does so electronically. A portal image (online portal image or digitized port film) is displayed side by side with a prescription image (digitized simulator film or digitally reconstructed radiograph). The user can measure distances between features in prescription and portal images and "write" on the display, either to approve the image or to indicate required corrective actions. The EVB tool also provides several features not available in conventional verification practice using a light box. METHODS AND MATERIALS: The EVB tool has been written in ANSI C using the X window system. The tool makes use of the Virtual Machine Platform and Foundation Library specifications of the NCI sponsored Radiation Therapy Planning Tools Collaborative Working Group for portability into an arbitrary treatment planning system that conforms to these specifications. The present EVB tool is based on an earlier Verification Image Review tool, but with a substantial redesign of the user interface. A graphical user interface prototyping system was used in iteratively refining the tool layout to allow rapid modifications of the interface in response to user comments. RESULTS: Features of the EVB tool include 1) hierarchical selection of digital portal images based on physician name, patient name, and field identifier; 2) side-by-side presentation of prescription and portal images at equal magnification and orientation, and with independent grayscale controls; 3) "trace" facility for outlining anatomical structures; 4) "ruler" facility for measuring distances; 5) zoomed display of corresponding regions in both images; 6) image contrast enhancement; and 7) communication of portal image evaluation results (approval, block modification, repeat image acquisition, etc.). CONCLUSION: The EVB tool facilitates the rapid comparison of prescription and portal images and permits electronic communication of corrections in port shape and positioning. PMID- 7995746 TI - Dose uniformity in a planar interstitial implant system. AB - PURPOSE: This work makes use of a volume-ratio technique to examine dose uniformity in a planar interstitial implant system based entirely on geometrical constraints. The rationale for determining an upper limit for acceptable dose variation is examined and discussed. Variation of ribbon spacing and interplanar separation is evaluated in terms of its effect on dose homogeneity. METHODS AND MATERIALS: Volume-dose curves were generated for a range of planar implant dimensions. The volume inside the target region and enclosed between the reference isodose and a higher isodose surface was calculated as a measure of dose uniformity. Studies of homogeneity, target coverage, and external tissue irradiation were carried out to evaluate the importance of flexible interplanar spacing in optimizing implants. New dose tables were generated to accommodate the frequent clinical need to minimize the number of catheter insertions. RESULTS: Implants carried out in accordance with specified geometric constraints were found also to provide optimal dose homogeneity as determined using the volume ratio method with a flexible high dose limit. For two-plane implants, the interplanar spacing should be determined specifically in each case to ensure accurate target coverage. Calculations for specific cases showed that the tissue volume treated to unnecessarily high dose levels can be reduced by a large factor by careful positioning of the implant planes. A smaller ribbon and seed spacing will, in general, lead to better dose uniformity when this is evaluated in terms of the volumes treated to very high dose levels. CONCLUSIONS: Our studies showed that implants carried out using simple and useful geometric guidelines will also provide an acceptably uniform dose distribution. For double plane implants, the separation of the implant planes should be optimized for each target thickness. PMID- 7995745 TI - The effectiveness of immobilization during prostate irradiation. AB - PURPOSE: To evaluate the effect of a hemibody foam cradle on the reproducibility of patient setup during external beam radiation treatment of prostate cancer. METHODS AND MATERIALS: Between January 1992 and April 1993, 74 patients received external beam radiation treatment to the prostate +/- nodes, generally with a four-field box technique. Forty-four of the 74 patients had a custom-made hemibody foam cast used in an attempt to improve setup accuracy. A review of the routine weekly port films was performed following the completion of therapy to determine the reproducibility of patient setup in all 74 patients. The physician's request of an isocenter shift was used as an indicator of reproducibility. Neither the treating technologists nor the physicians knew at the time the films were taken that the port films would be reviewed for setup reproducibility at a later date. The results were compared between the patients treated with (44) and without (30) an immobilization device. RESULTS: In the 44 immobilized patients, 213 routine checks of the isocenter were performed during the 7-week course of radiation therapy. In 17.4% of these instances (37 out of 213), an isocenter shift was requested. This rate is compared to 23.1% (30 out of 130) in the 30 patients who did not have the immobilization device (p < 0.2). There was a statistically significant reduction in isocenter shifts requested in the anterior to posterior direction in the patients who were immobilized, 5.1% (9 out of 175) vs. 12.6% (13 out of 103) (p < 0.05, two tailed chi-square test). There was no significant improvement in the reproducibility of isocenter placement in the cephalad to caudal or right to left directions. CONCLUSIONS: This custom-made hemibody foam cradle appears to improve the reproducibility of patient setup during the 7-week course of fractionated external beam irradiation for patients with adenocarcinoma of the prostate. This type of immobilization device is now routinely used in our clinic and is recommended for all patients receiving pelvic radiotherapy. These devices are likely to be particularly useful when contemplating dose escalation to minimize the volume of bladder and rectum included in the treatment fields. PMID- 7995747 TI - Optimum field size and choice of isodose lines in electron beam treatment. AB - PURPOSE: A method is provided for the optimum field size and the choice of isodose line for the dose prescription in electron beam therapy. METHODS AND MATERIALS: Electron beam dose uniformity was defined in terms of target coverage factor (TCF) which is an index of dose coverage of a given treatment volume. The TCF was studied with respect to the field size, the beam energy, and the isodose level for prescription from the measured data for various accelerators. The effect of the TCF on air gap between electron applicator/cone and the surface was investigated. Electron beams from scattering foil and scanned beam units were analyzed for the target coverage. RESULTS: A mathematical method is provided to optimize a field size for target coverage by a given isodose line in terms of TCF which is strongly dependent on the type of accelerator and the design of the collimator. For a given type of collimating system, the TCF does not depend on the type of electron beam production (scattering foil or swept scanned beam). Selection of isodose line for dose prescription is very critical for the value of the TCF and the dose coverage. The TCF is inversely proportional to the isodose value selected for the treatment and nearly linear with field size and beam energy. Air gap between applicator and the surface reduces the dose uniformity. Tertiary collimator moderately improves the lateral coverage for high energy beams. CONCLUSIONS: To adequately cover the target volume in electron beam treatment, lateral and depth coverage should be considered. The coverage at depth is strongly dependent on the choice of isodose line or beam normalization. If the dose prescription is at dmax (i.e., the 100% isodose line is selected), the choice of beam energy is not critical for depth coverage since dmax is nearly independent of energy for smaller fields. The 100% isodose line should not be chosen for treatment because of the significant constriction of this isodose line and inadequate coverage at depth. For a higher TCF, a minimum air gap between the cone to the surface of the patient is desired. If such is not possible, then a tertiary collimator at the skin is required. Whenever, a tertiary collimator is used, it is advised to increase the collimator field size by a factor of 1.4. PMID- 7995748 TI - Comparison of high dose-rate and low dose-rate dose distributions for vaginal cylinders. AB - PURPOSE: The identification of appropriate high dose-rate parameters required to produce a "uniform" dose distribution on the surface of a vaginal cylinder. The high dose-rate dose distribution is then compared to the traditional low dose rate dose distributions obtained with Burnett cylinders. METHODS AND MATERIALS: Dose distributions were calculated for 2, 3, and 3.5 cm diameter Burnett cylinders with and without crossing sources. Three models for the high dose-rate cylinders were developed and compared. High dose-rate dose distributions were calculated for 2, 3, and 3.5 cm diameter cylinders with and without anisotropic corrections for various dose specification points. RESULTS: Low dose-rate distributions are not uniform over the surface of the applicator. The exact distribution depends upon cylinder diameter and upon the exact source loading. High dose rate dose distributions can be configured to provide for a "uniform" dose on the surface, if an apex dose specification point is used together with dose specification points on the surface of the applicator opposite each dwell position. CONCLUSIONS: The conversion of low dose rate techniques to high dose rate techniques for vaginal cylinders involves an appreciation of the details of dose distributions of both approaches. The comparison between traditional low dose-rate distributions and high dose-rate distributions shows that, unlike the low dose-rate distributions, a relatively uniform high dose-rate distribution can be obtained independent of cylinder diameter. The clinical significance of the differences in the low dose-rate and high dose-rate dose distributions remains to be determined by long-term follow up of patients treated with high dose-rate techniques. PMID- 7995749 TI - Dosimetric consequences of 10B(n, alpha)7Li reaction occurring at the cellular membrane. AB - PURPOSE: Microdosimetric expectations of Boron contents are extracted from a CRAY Monte Carlo simulation of the nuclear reaction 10B(n, alpha)7Li as it occurs on a boronated membrane of a model cell and as the reaction fragments (alpha and Li) traverse into the cellular nucleus. METHODS AND MATERIALS: The present microdosimetry calculation is based upon the assumption that the therapeutic advantage of boron neutron capture therapy (BNCT), while depending upon the RBE and LET of the reaction particles, is equally dependent on the boron carrier preferential localization to tumor tissue, and the boron selectivity to cancerous cells and its specificity within subcellular compartments. In particular, boron fixes to cell membrane as it ought to, using monoclonal antibodies. The present Monte Carlo simulation computes stochastic expectations of alpha/Li energy depositions to the nucleus in a uniformly boronated membrane shell of a spherical cell. Differential energy gain was deduced from the stochastic energy depositions in events of neutron reactions with membrane boron compared against those with natural elements (O, H, N) in the cell. RESULTS: Microdosimetry data are presented in terms of specific energy (keV/micron3) and lineal energy (keV/micron) functions of the nucleus-to-cell volume ratios (NCVR). When folded with the geometric boron content and accounting for background reaction energies, the distributions yield effective energy gain to the cell nucleus per neutron capture event. Boron amount required to yield these energy gains are found to be of the order of picograms of boron per gram of cell mass. CONCLUSION: The boron content as inferred by the present Monte Carlo microdosimetry compares well with that deliverable by present pharmacokinetic means, but are orders of magnitude (mu-grams) less than those deduced previously from anthropomorphic macrodosimetry. PMID- 7995750 TI - Very fast simulated reannealing in radiation therapy treatment plan optimization. AB - PURPOSE: Very Fast Simulated Reannealing is a relatively new (1989) and sophisticated algorithm for simulated annealing applications. It offers the advantages of annealing methods while requiring shorter execution times. The purpose of this investigation was to adapt Very Fast Simulated Reannealing to conformal treatment planning optimization. METHODS AND MATERIALS: We used Very Fast Simulated Reannealing to optimize treatments for three clinical cases with two different cost functions. The first cost function was linear (minimum target dose) with nonlinear dose-volume normal tissue constraints. The second cost function (probability of uncomplicated local control) was a weighted product of normal tissue complication probabilities and the tumor control probability. RESULTS: For the cost functions used in this study, the Very Fast Simulated Reannealing algorithm achieved results within 5-10% of the final solution (100,000 iterations) after 1000 iterations and within 3-5% of the final solution after 5000-10000 iterations. These solutions were superior to those produced by a conventional treatment plan based on an analysis of the resulting dose-volume histograms. However, this technique is a stochastic method and results vary in a statistical manner. Successive solutions may differ by up to 10%. CONCLUSION: Very Fast Simulated Reannealing, with modifications, is suitable for radiation therapy treatment planning optimization. It produced results within 3-10% of the optimal solution, produced using another optimization algorithm (Mixed Integer Programming), in clinically useful execution times. PMID- 7995751 TI - Are half-times of repair reliably shorter for tumors than for late normal-tissue effects? PMID- 7995752 TI - In search of the "quality" in quality-of-life research. PMID- 7995753 TI - Can total body irradiation be supplanted by busulfan in cytoreductive regimens for bone marrow transplantation? PMID- 7995754 TI - Androgen ablation--50 years later. PMID- 7995756 TI - In response to Leibel et al. PMID- 7995755 TI - Potential reduced late effects for pulsed brachytherapy compared with conventional LDR. PMID- 7995757 TI - In response to Rescigno et al. PMID- 7995758 TI - Further characterization of postradiotherapy cellulitis and efforts at prevention. PMID- 7995760 TI - Neutron therapy in prostate cancer--is the therapeutic ratio improved? PMID- 7995759 TI - In response to Rescigno et al. PMID- 7995761 TI - The importance of incomplete repair, interfraction interval, and fractional dose. PMID- 7995762 TI - Markers, CTs, urethrograms, and the prostatic apex. PMID- 7995763 TI - Vasoactivity, a potentially important variable in the sequencing of tirapazamine (SR 4233) and radiation. PMID- 7995764 TI - Factors influencing incidence of acute grade 2 morbidity in conformal and standard radiation treatment of prostate cancer. AB - PURPOSE: The fundament hypothesis of conformal radiation therapy is that tumor control can be increased by using conformal treatment techniques that allow a higher tumor dose while maintaining an acceptable level of complications. To test this hypothesis, it is necessary first to estimate the incidence of morbidity for both standard and conformal fields. In this study, we examine factors that influence the incidence of acute grade 2 morbidity in patients treated with conformal and standard radiation treatment for prostate cancer. METHODS AND MATERIALS: Two hundred and forty-seven consecutive patients treated with conformal technique are combined with and compared to 162 consecutive patients treated with standard techniques. The conformal technique includes special immobilization by a cast, careful identification of the target volume in three dimensions, localization of the inferior border of the prostate using the retrograde urethrogram, and individually shaped portals that conform to the Planning Target Volume (PTV). Univariate analysis compares differences in the incidence of RTOG-EORTC grade two acute morbidity by technique, T stage, age, irradiated volume, and dose. Multivariate logistic regression includes these same variables. RESULTS: In nearly all categories, the conformal treatment group experienced significantly fewer acute grade 2 complications than the standard treatment group. Only volume (prostate +/- whole pelvis) and technique (conformal vs. standard) were significantly related to incidence of morbidity on multivariate analysis. When dose is treated as a continuous variable (rather than being dichotomized into two levels), a trend is observed on multivariate analysis, but it does not reach significant levels. The incidence of acute grade 2 morbidity in patients 65 years or older is significantly reduced by use of the conformal technique. CONCLUSION: The conformal technique is associated with fewer grade 2 acute toxicities for all patients. This conclusion is valid irrespective of selection criteria except in a few cases. Older age is associated with increased toxicity only with the standard technique and not then at a statistically significant level. Elderly patients should not be excluded from external beam radiation because of increased morbidity especially if conformal treatment is available. Volume is not significantly related to morbidity in patients with standard treatment, but it is for conformal treatment. Furthermore, it remains significant in a multivariate analysis that also shows the advantage of conformal treatment. Grade 2 acute toxicities are more volume dependent than dose dependent. PMID- 7995765 TI - Node-positive cervical cancer: impact of pelvic irradiation and patterns of failure. AB - PURPOSE: The roles of postoperative pelvic and prophylactic paraaortic irradiation in pelvic node positive cervical cancer are currently controversial. A retrospective study was undertaken to examine the effect of pelvic irradiation on pelvic control and survival and to analyze the patterns of recurrence to determine whether indications exist for prophylactic paraaortic irradiation. METHODS AND MATERIALS: From 1964 to 1991, 143 cases of FIGO Stage I and II cervical cancer undergoing exploratory laparotomy, pelvic lymph node dissection, and radical hysterectomy had positive pelvic lymph nodes. Postoperatively, 108 cases were treated with whole pelvic irradiation while 35 patients were observed. Prophylactic paraaortic irradiation was not given. RESULTS: Patients who received postoperative whole pelvic irradiation compared with those treated with radical hysterectomy alone had a significantly improved pelvic control rate, disease-free survival (DFS), and overall survival. The 5-year actuarial pelvic control rate was 78% vs. 45% (p = < 0.0001), respectively. The 5-year actuarial DFS was 65% vs. 41% (p = 0.0004). The 5-year actuarial overall survival was 58% vs. 46% (p = 0.02). In multivariate analysis, pelvic irradiation continued to show a positive effect on DFS (p = 0.0001) and overall survival (p = 0.0035). Lymphatic invasion and the total number of positive lymph nodes were the only other independent predictors of overall survival and DFS. The actuarial 5-year pelvic, paraaortic, and distant failure rates were 30%, 10%, and 28%, respectively. An isolated first recurrence in the paraaortic nodes occurred in only three cases. CONCLUSION: Postoperative pelvic irradiation significantly improves pelvic control, DFS, and overall survival, and should be used in patients with early stage cervical cancer and pathologically proven pelvic nodal metastases. The low incidence of isolated paraaortic nodal failure calls into question the value of routine prophylactic paraaortic irradiation in these patients. PMID- 7995766 TI - Brachytherapy-related complications for medically inoperable stage I endometrial carcinoma. AB - PURPOSE: The current study was conducted to investigate the incidence and risk factors for medical complications associated with low dose rate brachytherapy in patients with medically inoperable Stage I endometrial cancer treated with irradiation alone. METHODS AND MATERIALS: From 1965 through 1991 at Mallinckrodt Institute of Radiology, 150 implants were performed on 96 patients who were deemed medically unfit for hysterectomy because of advanced age, obesity, and various medical problems. The records of these patients were examined retrospectively to determine the incidence of medical complications that occurred in the first 30 days following the initiation of brachytherapy. The association of risk factors that precluded major surgery and the occurrence of brachytherapy related complications was examined by logistic regression. RESULTS: Of these 96 patients, 40 patients were older than 75 years, and 31 patients were deemed morbidly obese. Medical problems included hypertension in 45 patients, and diabetes in 37; there was a history of congestive heart failure in 23, stroke in 11, myocardial infarction in 10, and thromboembolism in 8. There were concurrent malignancies in five patients. Implants were performed using intrauterine Simon Heyman capsules, tandems, and vaginal ovoids in all patients. General anesthesia was used for 98 implants, spinal anesthesia for 26, local anesthesia for 25, and epidural anesthesia for 1. The duration of anesthesia ranged from 30 to 120 min (median, 60 min). The duration of radioisotope application ranged from 11 to 96 h (median, 46 h). Preventive measures included low dose subcutaneous heparin in 55 patients (since 1978), and intermittent pneumatic compression boots in 29 (since 1985). Four patients developed life-threatening complications including myocardial infarction (two patients), congestive heart failure (one patient), and pulmonary embolism (one patient). Two of these four patients died; one with a myocardial infarction and the other with pulmonary embolism. The morbidity rate was thus 4.2% (4 out of 96), and the mortality was 2.1% (2 out of 96). Although the four serious complications occurred within 30 days of the procedure, only one complication and one death occurred during treatment. There was no correlation between occurrence of complications and medical risk factors, type and duration of anesthesia, or type and duration of implant. CONCLUSIONS: There is a low incidence of complications associated with conventional low dose rate brachytherapy. The procedure is well tolerated in patients with medically inoperable Stage I endometrial cancer. In comparison to the predicted serious complication rate of surgery in these patients, the number of life-threatening complications from brachytherapy appears to be quite acceptable. PMID- 7995767 TI - Role of postoperative radiation therapy after stabilization of fractures caused by metastatic disease. AB - PURPOSE: Although orthopedic stabilization is frequently performed for pathological fractures caused by metastatic disease, no data is available to support the value of postoperative radiation therapy (S+RT) in this setting. METHODS AND MATERIALS: We reviewed 64 orthopedic stabilization procedures in 60 consecutive patients with metastatic disease to previously unirradiated weight bearing bones with pathological or impending pathological fracture (femur 91%). Thirty-five sites that received adjuvant S+RT were compared to 29 sites that were treated with surgery alone (SA). Many potential prognostic variables were evaluated. Endpoints were: functional status (FS) of the extremity (1 = normal pain free use; 2 = normal use with pain, 3 = significantly limited use; 4 = nonfunctional extremity), subsequent orthopedic procedures to the same site, and survival following surgery. RESULTS: At the univariate level, S+RT (p = 0.02) and prefracture FS (p = 0.04) were the only significant predictors of patients achieving an FS of 1 or 2 after surgery. On multivariate analysis, only postoperative RT was significantly (p = 0.02) associated with attaining FS of 1 or 2 after surgery. The predicted probability of achieving FS 1 or 2 at any time was 53% for S+RT vs. 11.5% or SA (multiple logistic regression, p < 0.01). Evaluation of FS following surgery revealed that S+RT group had significantly better function in the 1-3, 3-6, and 6-12 month postoperative periods (chi square, p < 0.04 for each time period). Second orthopedic procedures to the same site were more common in the SA group than the S+RT group (log rank, p = 0.03). Actuarial median survival of S group was 3.3 months compared with 12.4 months for the S+RT group (log rank, p = 0.02), confirming the beneficial association with survival shown by the multivariate Cox regression analysis (p = 0.025). CONCLUSION: Although this retrospective study is subject to possible biases, several analyses adjusting for numerous prognostic factors uniformly indicate S+RT is the most important factor in patients achieving and maintaining normal functional status (+/- pain). Further, the S+RT group was associated with fewer orthopedic procedures as well as an improved overall survival. The improved survival may be due to (a) more favorable patients being referred for RT (possible section bias), or (b) improved functional status in the S+RT group. This study quantitatively supports the benefit of postoperative RT in this setting. PMID- 7995768 TI - The radiation response of the cervical spinal cord of the pig: effects of changing the irradiated volume. AB - PURPOSE: An investigation of the field size effect for the cervical spinal cord of the pig after single doses of gamma-rays. In this study, clinically relevant volumes of the spinal cord were irradiated. METHODS AND MATERIALS: The effects of the local irradiation of different lengths of the spinal cord (2.5 cm, 5.0 cm, and 10.0 cm) have been evaluated in mature pigs (37-43 weeks). Single doses of 25 31 Gy were given using a 60Co gamma-source, at a dose rate of 0.21-0.30 Gy/min. The incidence of radiation-induced paralysis was used as the endpoint. The data were analyzed using probit analysis and a normal tissue complication probability (NTCP)-model. RESULTS: Twenty-five animals out of a total of 53 developed paralysis, with histological evidence of parenchymal and vascular changes in their white matter. The slope of the dose-response curves decreased with the decrease in field size; however, there was no significant difference at the radiation dose associated with a 50% incidence of paralysis (ED50) irrespective of the method of analysis. The ED50 values +/- standard errors (+/- SE) were 27.02 +/- 0.36 Gy, 27.68 +/- 0.57 Gy, and 28.28 +/- 0.78 Gy for field lengths of 10, 5, and 2.5 cm, respectively. Analysis of the data with a normal tissue complication probability (NCTP) model gave similar results. The latent period for paralysis was 7.5-16.5 weeks with no significant differences between dose and field size. CONCLUSION: No significant field size-related differences in response were detectable in the cervical spinal cord of mature pigs after single dose irradiations, specifically at a clinically relevant level of effect (< ED10). PMID- 7995769 TI - Radiation-induced cognitive dysfunction: an experimental model in the old rat. AB - PURPOSE: To develop a model of radiation-induced behavioral dysfunction. METHODS AND MATERIALS: A course of whole brain radiation therapy (30 Gy/10 fractions/12 days) was administered to 26 Wistar rats ages 16-27 months, while 26 control rats received sham irradiation. Sequential behavioral studies including one-way avoidance, two-way avoidance, and a standard operant conditioning method (press lever avoidance) were undertaken. In addition, rats were studied in a water maze 7 months postradiation therapy. RESULTS: Prior to radiation therapy, both groups were similar. No difference was found 1 and 3 months postradiation therapy. At 6 7 months postradiation therapy, irradiated rats had a much lower percentage of avoidance than controls for one-way avoidance (23% vs. 55%, p < or = 0.001) and two-way avoidance (18% vs. 40%, p < or = 0.01). Seven months postradiation therapy the reaction time was increased (press-lever avoidance, 11.20 s vs. 8.43 s, p < or = 0.05) and the percentage of correct response was lower (water maze, 53% vs. 82%) in irradiated rats compared with controls. Pathological examination did not demonstrate abnormalities of the irradiated brains at the light microscopic level. CONCLUSION: Behavioral dysfunction affecting mainly memory can be demonstrated following conventional radiation therapy in old rats. This model can be used to study the pathogenesis of radiation-induced cognitive changes. PMID- 7995770 TI - Effect of pentoxifylline on radiation-induced lung and skin toxicity in rats. AB - PURPOSE: There is currently substantial clinical interest in pentoxifylline as an inhibitor of radiation-related normal tissue injury. To further assess this drug's potential toxicity-sparing effects, pentoxifylline was studied in rats using a radiation-induced lung injury model. METHODS AND MATERIALS: Adult male rats were exposed to either sham irradiation or a single fraction of 21 Gy delivered to the left hemithorax. Four study groups were defined: those that received neither radiation nor pentoxifylline, those that received pentoxifylline (500 mg/L in drinking water) but no irradiation, those that underwent irradiation without pentoxifylline, and those that received both pentoxifylline and radiation. Lung injury was measured by changes in relative left:right lung perfusion ratios derived from quantitative gamma camera imaging of 99mTechnetium macroaggregated albumin uptake in the pulmonary circulation. Serial scans were done over a 40-week period following radiation. Skin toxicity was also assessed. After 40 weeks, the animals were killed, and lung tissue was assayed for angiotensin converting enzyme activity as a marker for endothelial cell damage. RESULTS: Both groups of radiated (with or without pentoxifylline) rats showed equivalent acute sharp decreases in left:right lung perfusion ratios compared to the nonirradiated groups, reaching a mean nadir value of 0.29 at week 4. Irradiated lung perfusion in subsequent weeks in the radiation-only group showed minimal recovery, with a plateau mean ratio of 0.37 (0.36-0.39). However, there was apparent later recovery of lung perfusion in the radiation with pentoxifylline group from weeks 14 through 40, to a mean ratio of 0.47 (0.43 0.52) (p < 0.01 compared to the radiation-only group). Angiotensin converting enzyme activity correlated closely with lung perfusion data. No effect of pentoxifylline on acute or late skin toxicity was detected. CONCLUSIONS: This study suggests that pentoxifylline does not have any measurable effect on acute lung injury following hemithoracic irradiation in rats, but does result in sparing of later lung toxicity. PMID- 7995771 TI - Impact of "optimized" treatment planning for tandem and ring, and tandem and ovoids, using high dose rate brachytherapy for cervical cancer. AB - PURPOSE: Different treatment techniques are used in high dose rate (HDR) remote afterloading intracavitary brachytherapy for uterine cervical cancer. We have investigated the differences between "optimized" and "nonoptimized" therapy using both a tandem and ring (T/R) applicator, and a tandem and ovoids (T/O), applicator. METHODS AND MATERIALS: HDR afterloading brachytherapy using the Madison System for Stage IB cervical cancer was simulated for 10 different patients using both a T/R applicator and a T/O applicator. A treatment course consists of external beam irradiation and five insertions of HDR afterloading brachytherapy. Full dosimetry calculations were performed at the initial insertion for both applicators and used as a reference for the following four insertions of the appropriate applicator. Forty dosimetry calculations were performed to determine the dose delivered to Point M (similar to Point A), Point E (obturator lymph nodes), vaginal surface, bladder, and rectum. "Optimized" doses were specified to Point M and to the vaginal surface. "Nonoptimized" doses were specified to Point M only. Using the linear-quadratic equation, calculations have been performed to convert the delivered dose using HDR to the biologically equivalent doses at the conventional low dose rate (LDR) at 0.60 Gy/h. RESULTS: Major differences between "optimized" and "nonoptimized" LDR equivalent doses were found at the vaginal surface, bladder, and rectum. Overdoses at the vaginal surface, bladder, and rectum were calculated to be 208%, nil, and 42%, respectively, for the T/R applicator with "nonoptimization." However, for the T/O applicator, the overdoses were smaller, being nil, 32%, and 27%, respectively, with "nonoptimization." CONCLUSION: Doses given in high dose rate intracavitary brachytherapy border on tissue tolerance. "Optimization" of either applicator decreases the risk of a dose that may have potential for complications. Optimization of a tandem and ovoids best ensures that the doses are not diminished at the treatment sites, and that the potential for overdose is reduced. PMID- 7995772 TI - Preoperative radiation therapy and iododeoxyuridine for large retroperitoneal sarcomas. AB - PURPOSE: Local failure is frequent after conventional therapy for patients with retroperitoneal sarcomas. A Phase I/II multimodality approach was used, combining iododeoxyuridine (IdUrd) and radiation therapy, followed by attempted surgical resection, with the goal of improving local control. METHODS AND MATERIALS: Patients with retroperitoneal sarcomas were treated with three to five consecutive cycles of treatment. Each 14-day cycle consisted of a continuous intravenous infusion of IdUrd on days 1-5, twice a day radiation therapy (1.25 Gy/fraction) on days 8-12, and a break on day 13 and 14. Surgical resection was attempted after three or five cycles. Patients resected after three cycles received an additional two cycles of treatment with radiation directed to the tumor bed. IdUrd dose was escalated in Phase I fashion (1000 mg/m2/day, 1333 mg/m2/day, and 1600 mg/m2/day). The median potential follow-up was 31 months. RESULTS: Sixteen patients (13 with high grade tumors) were treated. The median maximum tumor size was 17 cm. Resection margins were negative in four patients, microscopically positive in four patients, and grossly positive in three patients. Five patients were not resected. The only grade 4 acute toxicity observed was vomiting which occurred in three patients receiving upper abdominal radiation. Postsurgical and long-term complications were rare. Median survival overall and for resected patients were 18 and 32 months, respectively. Local control was observed in three out of four patients with negative margins (9, 40+, and 51+ months), two out of four patients with microscopically positive margins (4 and 22 months), and one out of three patients with grossly positive margins (46+ months). The overall freedom from local progression was 45% at 24 months. CONCLUSION: Retroperitoneal sarcomas can be resected after preoperative radiation therapy and IdUrd, with encouraging local control in patients resected with negative or microscopically positive margins. The recommended dose using this drug and radiation schedule appears to be 1600 mg/m2/day, which will form the basis for a Phase II trial. PMID- 7995774 TI - Emotions and respiratory patterns: review and critical analysis. AB - The literature on emotions and respiration is reviewed. After the early years of experimental psychology, attention to their relationship has been sparse, presumably due to difficulties in adequate measurement of respiration. The available data suggest nevertheless that respiration patterns reflect the general dimensions of emotional response that are linked to response requirements of the emotional situations. It is suggested that the major dimensions are those of calm excitement, relaxation-tenseness, and active versus passive coping. Research on the emotion-respiration relationships has been largely restricted to the correlates of respiration rate, amplitude, and volume. Finer distinctions than those indicated may well be possible if a wider range of parameters, such as the form of the respiratory cycle, is included in the investigation. PMID- 7995773 TI - Inhaled recombinant interferon gamma in patients with lung cancer: pharmacokinetics and effects on chemiluminescence responses of alveolar macrophages and peripheral blood neutrophils and monocytes. AB - PURPOSE: A Phase I trial was conducted to investigate clinical toxicity, pharmacokinetics, and chemiluminescence (CL) responses of alveolar macrophages (AM) and peripheral blood neutrophils and monocytes after inhalation of recombinant interferon (r IFN)-gamma. METHODS AND MATERIALS: Eight patients with lung cancer inhaled r IFN-gamma as single doses of 0.1, 0.2, 0.6, 1.8, or 5.4 mg. Bronchoalveolar lavage was performed three times, 21 h before as well as 3 and 27 h after inhalation. RESULTS: Interferon-gamma was detectable in bronchoalveolar lavage fluid (BALF) samples taken 3 h after inhalation in doses of > or = 0.6 mg. Before inhalation, AM in four out of seven patients studied showed vigorous lucigenin-enhanced CL responses to N-formyl-methionyl-leucyl-phenylalanine and opsonized zymosan particles. Furthermore, the responses were markedly increased 3 h after inhalation. In three out of seven patients, AM in the pretreatment BALF samples showed low or no CL responses, and the responses did not increase after inhalation of IFN-gamma, suggesting that the patients were anergic. Postinhalation CL responses did not correlate with the dose of IFN-gamma inhaled. Circulating IFN-gamma was detected in one patient receiving the highest dose. No changes referable to IFN-gamma inhalation were found in the CL responses of blood neutrophils and monocytes. During the 24 h follow-up, two patients developed transient fever-reactions. CONCLUSIONS: The findings suggest that inhalation may provide a way to increase alveolar concentrations of IFN-gamma and to augment respiratory burst capacity of AM without any major side effects. This approach may have clinical implications for the treatment of tumors and infections of the respiratory tract. PMID- 7995775 TI - On the origin of the P3 event-related potential component. AB - Human findings indicate that the most important brain regions in the electrogenesis of the P3 event-related potential component are the junction of the parieto-temporal lobes, parts of the limbic system and some parts of the thalamus. Data collected in animal experiments support the results of the human studies emphasizing the role of the association cortical areas, that of limbic structures and possibly of some thalamic nuclei. It is not clear as yet how the activity of these hypothesized generators are integrated and to what extent, and how they contribute to the scalp-recorded P3. PMID- 7995776 TI - Feedback and autonomic awareness: the ability to discriminate the direction of spontaneous changes in peripheral body temperature. AB - Forty-eight Ss were requested to discriminate spontaneous changes of at least 0.1 degree C in their peripheral finger temperature (PFT). They were randomly assigned to one of 3 groups: in the first group ("KR") Ss were given a feedback after each discrimination; in the second group ("NKR") Ss were given no feedback after each discrimination; in the third group ("RKR") Ss were given a random feedback after each discrimination. Results indicated that in the "Knowledge-of Results" group discrimination was significantly higher than in both "No-Knowledge of-Results" and "Random-Knowledge-of-Results" groups. Within the first group, there was a significant difference in a discrimination index between Ss "aware" and Ss "unaware" of their PFT changes, which remained significant even when the effects of individual variability of PFT and of the regularity of PFT changes were partialled out. PMID- 7995777 TI - Reliability of an ambulatory electromyographic activity device for musculoskeletal pain disorders. AB - A number of investigators in recent years have called for the development of devices that can monitor surface EMG levels in individuals' normal environments for use with patients who suffer from disorders in which the etiology or maintenance of the pathology is presumed to be due at least in part to musculoskeletal dysfunction, such as low back pain, phantom limb pain and tension headache. This study examined the test-retest reliability of just such a device. Twenty-six healthy controls wore a lightweight (24 ounce) device which measured bilateral upper trapezius EMG, as well as peak and integral motion, for 5 consecutive days for up to 18 h each day. ANOVAs on the four measures revealed no difference between any of the four measures over the 5 days. Intra-class correlation coefficients for the two EMG variables across 5 days were both significant with alpha levels set at 0.01. The two EMG measures were highly correlated (r = 0.77); the two motion measures were also highly correlated (r = 0.60), but at a lower magnitude than EMG values; the relationship between EMG and motion was significant, but the magnitude of the between EMG motion correlations (0.26 and 0.35) were lower than the within EMG or motion ones. It was concluded that the test-retest reliability of the ambulatory monitoring device is within acceptable limits. Implications for the use of the device with musculoskeletal pain disorders--particularly headache--are discussed. PMID- 7995778 TI - Intertask consistency of hemodynamic responses to laboratory stressors in a biracial sample of men and women. AB - Cardiovascular responses were examined in a community sample of 128 subjects, comprised of 58 African American and 70 Caucasian American men and women. Subjects completed a battery of laboratory stressors including mental arithmetic, reaction time, a speech task, and the cold pressor test. In addition to systolic and diastolic blood pressures, the underlying hemodynamic parameters of cardiac output and total peripheral resistance were assessed. In order to explore intertask consistency of response in both ethnic groups and both gender groups, correlational analyses were conducted separately for each group. For the psychological tasks, unanimously significant coefficients were observed. Intertask consistency between psychological tasks and the cold pressor was also considerable, but was somewhat less impressive (particularly for blood pressure) than that observed among the psychological tasks themselves. With regard to hemodynamic responses, cardiac output and total peripheral resistance demonstrated intertask consistency equal to, if not greater than, that shown by systolic and diastolic blood pressure, this consistency being evident for each ethnic and each gender group. PMID- 7995779 TI - Endogenous components of event-related potential appearing during NREM stage 1 and REM sleep in man. AB - Information processing in the brain during sleep was studied by analyzing the evoked cortical response to auditory stimulations presented in the odd-ball paradigm. Eight subjects were examined in different sleep stages. The subjects could provide the correct behavioral response to the auditory stimulation by pressing a key button in the light part of stage 1 of NREM sleep, just succeeding to the waking state, but none of the subjects could give the correct behavioral response in the other sleep stages. In the deep part of stage 1 of NREM sleep and REM sleep, a cortical potential corresponding to P300, the endogenous component of the event-related potential (ERP) recorded in the waking state, was recorded in 6 of the 8 subjects in spite of the absence of the behavioral response. In stages 2, 3 and 4 of NREM sleep, emergence of this endogenous component of ERP could not be confirmed. The present findings provide electrophysiological evidence indicating that selective information processing corresponding to sensory discrimination of auditory stimuli is actively performed in stage 1 of NREM sleep and REM sleep. PMID- 7995780 TI - Long-term development for girls and boys at age 16-18 as related to birth weight and gestational age. AB - The present study was based on data from a longitudinal research program which consisted of 12,032 children, born in the Stockholm area in 1953 of which there were 494 children born with low birth weight (LBW, 2500 g or less). For all children at age 16 it was apparent that adjustment and psychiatric disturbances as well as juvenile delinquency were not related to birth weight and gestational age. LBW girls born at term, had significantly lower school grades, at age 16, than NBW (normal birth weight) girls. NBW boys born pre-term had lower school grades than NBW boys born at term. It is suggested that childhood development is gender related; in girls the birth weight--and in boys the length of the pregnancy was related to school marks at age 16. For boys at 18 years of age at the military draft, it was shown that LBW boys had smaller body size and lower IQ test scores as compared to NBW boys. Additionally the length of the pregnancy was related to some measures of body size but not to IQ-test scores. PMID- 7995782 TI - Making interdisciplinary education effective for rehabilitation students. AB - Interdisciplinary education has been recommended as a way of preparing students for team practice after graduation. There is debate in the literature over the best way to implement interdisciplinary education sessions, and many factors can influence their effectiveness. This paper is a case description report of a pilot project developed to promote interdisciplinary learning. The Northern Studies Stream of McMaster University's School of Occupational Therapy and Physiotherapy in Ontario, Canada developed a project that combined students from the occupational therapy and physiotherapy programs for small group tutorials held during clinical placements. The project incorporated suggestions from the literature in order to encourage cooperation and interdisciplinary learning. Participants were mature, second-degree students with similar levels of clinical experience. The sessions were a required part of the academic course, but were ungraded. Tutorials focused on issues relevant to clinical practice for both groups and were facilitated by faculty from both professions. Evaluation was positive, suggesting student characteristics (eg, level of experience and maturity) and session design features that may be helpful in planning future interdisciplinary education experiences. PMID- 7995781 TI - Physiological significance of the defense response to intense auditory stimulation: a pharmacological blockade study. AB - This paper examines through pharmacological blockade some questions related to the physiological significance of the defense response to intense auditory stimulation. Nine subjects received intravenous metoprolol (10-15 mg i.v.), intravenous atropine (0.03 mg/kg i.v.), or a saline solution as placebo condition before undertaking a test of the defense response to a distorted sound of 400 Hz frequency, 109 dB intensity, 0.5 sec duration and virtually instantaneous risetime. Dependent variables were continuous (beat-to-beat) heart rate, stroke volume and blood pressure. The results suggest: (1) a vagal origen of the first acceleration and first deceleration and a sympathetic-parasympathetic interaction during the second acceleration and second deceleration of the heart rate response; (2) a blood pressure response pattern characterized by an increase during the first heart rate deceleration (4-11 sec), a posterior decrease coinciding with the second heart rate acceleration (from 12 to 37 sec), and a lighter increase during the second heart rate deceleration (from 38 to 63 sec); and (3) an implication of the baroreceptor reflex, including a baroreceptor mediated inhibition of the parasympathetic cardiac activity during the second accelerative component of the cardiac response. PMID- 7995783 TI - Rural and urban differences in employment and vacancies in ten allied health professions. AB - Few studies examine rural and urban differences in supply and demand for allied health professionals. This research examined ten allied health professions for rural and urban differences in employment and vacancies across four types of hospital settings. Based on data from a Georgia workforce study, significant differences in employment rates were noted for medical technologists, medical laboratory technicians, licensed practical nurses, registered nurses, and social workers. Significant size x location differences in vacancy rates were found for registered nurses and respiratory therapists. This study suggests that rurality and hospital size may impact levels of employment and vacancies in selected professions, and that a detailed workforce analysis is needed by profession, employment sector, and geographical area to establish a clear picture of health care services needed by the population. PMID- 7995784 TI - Intrinsic and extrinsic predictors of work satisfaction in ambulatory care and hospital settings. AB - This study assessed the ability of selected intrinsic and extrinsic variables to predict allied health practitioners' work satisfaction in ambulatory care and hospital settings. A total of 413 occupational and physical therapists in Virginia, North Carolina, and South Carolina provided data via a mailed survey. Multiple regression analyses examined the predictive power of selected intrinsic and extrinsic variables upon therapists' work satisfaction in the ambulatory care and hospital setting. The regression model for therapists in ambulatory care settings was a better predictor of work satisfaction than the model for therapists in the hospital setting. Results indicated that respondents' intrinsic orientation toward their work, and their perception of the general working conditions in the organization were two of the strongest predictors of their work satisfaction in the ambulatory care and hospital setting. The findings provide information that can be useful in developing recruitment and retention strategies in both work settings. PMID- 7995785 TI - A view from Washington -- health care reform update: the long battle. PMID- 7995786 TI - The Americans with Disabilities Act: allied health educators' responsibility and challenge. PMID- 7995787 TI - What is the outcome for children's mental health needs in national health care reform? PMID- 7995789 TI - Psychophysiologic reactivity in asthmatic children: a cholinergically mediated confluence of pathways. AB - OBJECTIVE: The purpose of this study was to determine the suitability of a newly developed experimental paradigm, designed to assess relationships among emotional responsivity, physiologic (autonomic) reactivity, airway reactivity, and pulmonary function in asthmatic children under controlled conditions of ecologically valid emotional stimulation. METHOD: Twenty-four children, aged 8 through 17, with moderate to severe asthma viewed the movie, E.T., the Extra Terrestrial, while having their heart and respiration rate and oxygen saturation continuously measured and recorded. Airway reactivity was assessed by the methacholine challenge test, and pre- and postmovie pulmonary function by spirometry. Self-report of emotion was recorded for targeted scenes. RESULTS: Findings indicated that emotional responsivity and physiologic reactivity to the movie were associated with increased airway reactivity and with decreased pulmonary function. CONCLUSIONS: The pattern of results suggests cholinergically mediated psychophysiologic pathways of emotional influence in the asthmatic process for some asthmatic children. A heuristic biopsychosocial model of these pathways is presented. PMID- 7995788 TI - Somatization in children and adolescents. AB - OBJECTIVE: To review the empirical literature on somatization in the pediatric age group, emphasizing prevalence, influence on health care utilization, issues in the development of somatization, comorbidity with other psychiatric disorders, assessment, and treatment. METHOD: One hundred nineteen studies and reports addressing medically unexplained somatic symptoms in children and adolescents were compiled via MEDLINE search and extensive cross-referencing. All available controlled studies were included, as were selected case reports and collections of cases. Selected citations from the adult literature were chosen for relevance to pediatric somatization. RESULTS: Recurrent, medically unexplained physical symptoms are common in the pediatric age group, are often associated with other psychiatric symptoms, and may represent a common presentation of psychiatric disorder in the primary care setting. DSM-III-R-defined somatization disorder is rare, and pseudoneurological symptoms are unusual. Patients may be at risk for potentially dangerous, costly, and unnecessary medical investigations and treatments, and they may excessively utilize health care services. CONCLUSION: Our current understanding of pediatric somatization and its consequences is limited. Collaboration between mental health professionals and primary health care providers is essential. Consistent terminology, developmentally appropriate classification, and systematic future research will be necessary for the development of successful prevention and treatment strategies. PMID- 7995790 TI - Predictors of coping with pain in mothers and their children with sickle cell syndrome. AB - OBJECTIVE: This study examined predictors of strategies used to cope with pain in children with sickle cell disease and their mothers. METHOD: Disease severity, socioeconomic status, child adjustment and adaptive behavior, maternal psychopathology, and family functioning were examined in 55 mother-child dyads to determine the predictive potential of these factors on engagement and disengagement coping. RESULTS: While controlling for socioeconomic status and psychopathology in the mothers, 15% of the variance in engagement coping was predicted by family adaptability. Disengagement coping was predicted by internalizing symptoms exhibited by the child, including a negative and pessimistic attributional style, which accounted for nearly one fifth of the variance. Finally, mothers who reported more active strategies for coping with their child's pain were more likely to endorse greater use of techniques to prevent and effectively manage pain in their children. CONCLUSIONS: Neither coping strategy was predicted by severity of disease presentation in the children, suggesting the importance of psychosocial factors in adapting to childhood chronic illness and that severity of disease may not necessarily be a marker for families at risk for adjustment difficulties. Findings were interpreted to support a systemic family model in promoting active and adaptive engagement coping in caretakers of children with sickle cell syndrome. PMID- 7995791 TI - Social dysfunction and psychiatric disorder in mothers and their children. AB - OBJECTIVE: The authors examine (1) the reliability and validity of the Adult Personality Functioning Assessment (APFA) as a retrospective measure of baseline social dysfunction in adults; and (2) the association between mothers' APFA scores and psychiatric disorders and functioning in their children. METHOD: The subjects (50 mothers and their children) are a subsample of a larger family genetic study which examined the relationship between panic disorder and major depression in probands and their first-degree relatives. RESULTS: The APFA demonstrates good interrater reliability for its subscale domains as well as construct validity. Children of psychiatrically ill parents, regardless of disorder, are not all alike in their response to maternal disorder and functioning. The level of impact of mothers' impaired baseline functioning varies according to maternal psychiatric diagnosis. There is less impact of maternal functioning on children of depressed mothers compared to children of anxious mothers. Poor maternal baseline functioning may signal the increased need for treatment for children exposed to chronically dysfunctional parents indicated by the children's increased enrollment in therapy and their rates of suicidality. CONCLUSION: Parent and child adaptation appears intertwined, and intervention in one is likely to affect functioning in another. Specifically, intervention in parental social functioning may decrease the risk for disorder and dysfunction in offspring. Clinical and research implications are discussed. PMID- 7995792 TI - Mothers' expressed attitudes: associations with maternal depression and children's self-esteem and psychopathology. AB - OBJECTIVE: Mothers' expressed attitudes about their children were examined to discern whether the associations between maternal depression and children's psychopathology and self-esteem might be modified by the mother's expression of critical attitudes. METHOD: Mother-child dyads with mothers who had a history of at least one episode of unipolar major depression during the child's lifetime (N = 20) were compared to dyads with well parents (N = 19). Children's ages ranged from 8 to 10 years. Mothers' attitudes toward their children were derived from semistructured interviews. The affect expressed in each maternal statement was coded as neutral, positive, descriptive negative, or affectively charged negative. RESULTS: Affectively charged negative statements were found to be associated with mothers with a history of depressive episodes. A tendency was noted for the highest rates of psychopathology to be among children of depressed mothers who used affective-negative statements. Mothers' use of affectively charged negatives was found to modify the association between maternal depression and children's lower global self-worth. CONCLUSIONS: Clinicians attuned to mothers' expression of critical attitudes toward their children might detect children at risk for lowered self-esteem and the development of psychopathology. PMID- 7995793 TI - Parent-child agreement in prepubertal depression: findings with a modified assessment method. AB - OBJECTIVE: Lack of or low parent-child (P-C) agreement is a well-documented problem in child psychopathology assessment. This study proposed to improve this agreement by using a modified assessment approach. METHOD: Ninety-three depressed prepubertal children, aged 6 to 12 years, and their mothers underwent an assessment procedure that combined multiple assessment measures given separately to child and mother (Schedule for Affective Disorders and Schizophrenia for School-Age Children-Present Episode [K-SADS-P], Children's Depression Inventory, and traditional psychiatric interviews), confrontation of either and/or both informants with intra- and interinformant discrepancies, and senior clinician's "best estimate" clinical judgment to solve discrepant ratings. Correlational statistics (r, kappa, and z) were used to compare child's with mother's ratings on 20 K-SADS-P depressive symptoms. RESULTS: The major hypothesis, that using our assessment procedure, P-C agreement would be significant and moderately high (r and kappa = .40 or higher), was confirmed. The second hypothesis on dissociation of P-C agreement on behavioral versus ideational symptoms was partially confirmed; the third hypothesis on adverse effects of maternal "depression" on P C agreement was not confirmed. CONCLUSION: Our assessment method has potential clinical application in enhancing diagnostic reliability of childhood depression assessment. PMID- 7995794 TI - Gender and the comparison of self and observer ratings of anxiety and depression in adolescents. AB - OBJECTIVE: This study assessed the influence of gender on the comparability of self and observer ratings of anxiety and depression in adolescents. METHOD: Subjects were 75 inpatient adolescents who were administered structured interviews of the revised Hamilton Rating Scales for Depression (HRSD-R) and Anxiety (HARS-R) and read the Beck Depression Inventory (BDI) and Beck Anxiety Inventory (BAI). RESULTS: All measures demonstrated adequate internal consistency and validity. The correlation between the BDI and HRSD-R was significantly higher for females than males; of 11 symptoms that overlap on the BDI and HRSD-R, observers significantly agreed with males and females in their perceptions of 5 and 11 depressive symptoms, respectively. The correlation between the BAI and HARS-R did not differ significantly for males and females. CONCLUSIONS: Results suggest that self-reports of anxiety symptoms are a valid, cost-effective alternative to anxiety observer ratings for boys and girls' self-reports of depression are comparable to depression ratings by observers. There is the need to collect self-report information from adolescent boys because they may not communicate subjective symptoms of depression, e.g., guilt, to observers. PMID- 7995795 TI - Are adolescents changed by an episode of major depression? AB - OBJECTIVE: This study examined whether adolescents having a first onset of major depression are changed by the experience (i.e., does having an episode of depression result in residual effects that did not exist before the episode?). METHOD: Among 1,507 community adolescents assessed at two time points approximately 1 year apart 45 experienced and recovered from a first episode of depression between the two assessments. These adolescents were contrasted with never-depressed control subjects on an array of depression-related psychosocial variables before and after the episode. RESULTS: Psychosocial scars (characteristics evident after but not before the episode) included internalizing behavior problems, stressful major life events, excessive emotional reliance on others, cigarette smoking and subsyndromal depression symptoms. Both before and after the episode, the depressed adolescents reported an elevated level of physical health problems. CONCLUSIONS: More scars were found in the present study than in previous research with formerly depressed adults. This is consistent with the hypothesis that early-onset depression is a more pernicious form of the disorder that may impact adolescents more severely than adults. PMID- 7995796 TI - Clozapine treatment of bipolar disorder in a young adolescent. AB - A 13-year-old boy with a 4-year history of bipolar disorder and concomitant obsessive-compulsive disorder required four hospitalizations and two partial hospitalizations due to inadequate responses to combinations of neuroleptics and traditional treatments for bipolar disorder. The use of clozapine in combination with lithium and clomipramine facilitated successful discharge from the hospital and return to a structured school setting. Significant adverse affects from interactions between valproic acid and clozapine necessitated discontinuation of valproic acid. PMID- 7995797 TI - Fluoxetine-induced memory impairment in an adolescent. AB - This paper describes a 14-year-old male patient who complained of memory problems during treatment with fluoxetine for major depression. The patient showed impairments on all five scales of the Wechsler Memory Scale-Revised during fluoxetine treatment. Three of the scales, Verbal Memory, Visual Memory, and General Memory, showed statistically significant improvements after fluoxetine was discontinued. This case represents the first time memory deficits related to fluoxetine were quantitated with a standardized memory test. It points to cognitive side effects that need to be understood. PMID- 7995798 TI - Language and behavior in children with Sotos syndrome. AB - OBJECTIVE: To examine language and behavior in children with Sotos syndrome, an overgrowth syndrome involving advanced bone age, characteristic facies, and developmental disability. METHOD: Twenty-seven children with Sotos syndrome were compared with 20 children with overgrowth, intellectual disability, and facies not characteristic of Sotos syndrome. Ages ranged from 5 to 16 years. Direct assessment was undertaken with standardized measures of intelligence and language abilities. Behavior was examined by parent and teacher report. RESULTS: Children with Sotos syndrome had levels of intelligence in the severely disabled to average range, with the majority falling in the borderline range. Mean level of intelligence was significantly higher than that observed for children in the comparison group. Language abilities were developed to a level consistent with overall level of intelligence. Rates of parent- and teacher-reported behavior problems were significantly higher than normal, but, with the exception of temper tantrums, did not differ from those observed in children in the comparison group. Attention-deficit hyperactivity disorder was observed in 38% of children with Sotos syndrome. They were more irritable and had more stereotypic behavior and inappropriate speech than is expected in children with intellectual disabilities, and they were more withdrawn and had more stereotypic behavior than children in the comparison group. CONCLUSIONS: Assessment of language abilities revealed no specific language impairment. High rates of behavior problems were observed, but these were not higher than those observed for other large, delayed, dysmorphic children. PMID- 7995799 TI - Fragile X syndrome in a normal IQ male with learning and emotional problems. AB - The present case study features an adult male who was diagnosed with fragile X syndrome after the identification of this syndrome in his more affected brother. The patient presented with a Full Scale IQ within the broad range of normal and has been diagnosed with a schizotypal personality disorder. He shows significant deficits in the social and emotional aspects of daily life, but has striking cognitive strengths relating to reading and vocabulary as compared to most males affected with fragile X syndrome. DNA testing of blood leukocytes revealed that he has a fully expanded FMR1 CGG repeat mutation associated with almost complete lack of methylation. Protein studies demonstrate a limited production of FMRP, the protein produced by the FMR1 gene. It is believed that the near absence of methylation of the fully expanded mutation and the resultant expression of the FMR1 protein is responsible for the strong cognitive abilities of this fragile X patient. PMID- 7995801 TI - Language disorders and learning disabilities in school-refusing adolescents. AB - OBJECTIVE: We undertook this study to test the hypothesis that school-refusing adolescents hospitalized on an inpatient psychiatric unit have more language and learning disabilities than diagnosis-, age-, and sex-matched psychiatric controls. METHOD: The Woodcock-Johnson Tests of Achievement-Revised (WJTA-R), the WISC-R, the Adolescent Language Screening Test, the Clinical Evaluation of Language Fundamentals-Revised, and the Test of Language Competence (TLC) were given to a group of well-characterized, primarily depressed school refusers and matched psychiatric controls. RESULTS: We found that school-refusing adolescents had significantly lower WISC-R verbal intelligence scores, lower Math and Written Language subscale scores on the WJTA-R, and lower scores on the TLC than nonrefusers. School refusers were found to have a significantly higher incidence of both language impairments and learning disabilities than controls. CONCLUSIONS: We infer that academic and communicative frustration and the adolescent's resulting inability to meet the academic and social demands in the school environment may play a role in the etiology of school refusal. PMID- 7995800 TI - Seven-year follow-up of speech/language-impaired and control children: speech/language stability and outcome. AB - OBJECTIVE: This study examined the 7-year outcome of speech/language (S/L) impaired and control children selected from a community sample at age 5 years. METHOD: Two hundred fifteen children completed a variety of speech and language tests at age 12 years. Children with S/L impairment were further classified as "speech only," "language only," or "speech and language impaired." RESULTS: More than 72% of children who had S/L impairment at age 5 remained impaired at age 12. Children with both speech and language problems were most likely to remain S/L impaired; 81% had some kind of S/L impairment at follow-up. Similarly, children with both expressive and receptive language impairment were more likely to show expressive or receptive impairment at follow-up than children with expressive impairment alone. One third of time 1 controls had S/L problems at follow-up, and of these 82% had speech impairment only. CONCLUSIONS: S/L impairment identified at age 5 has long-lasting effects. More pervasive problems were associated with poorer outcomes. Screening at age 5 may be useful, as most serious S/L problems that emerged by middle childhood could be identified at age 5. The effects of S/L treatment require further study. PMID- 7995802 TI - The vitamin and mineral mystery. PMID- 7995803 TI - Is lithium therapy justified? PMID- 7995804 TI - Behavioral treatment for autism. PMID- 7995805 TI - ECG and clonidine. PMID- 7995806 TI - Mediated realism and the representation of a health care controversy. AB - Psychologists have recently identified "situated cognition" as an important issue for educators across disciplines. Accordingly, instructional technologists have been working on ways to make classroom materials more true-to-life and affectively engaging. In this article I review a study designed to investigate the ways in which differing realism conditions (delivered through interactive video) influenced users' understanding of the issue of euthanasia and the case of Dax Cowart. Based on the study's findings, I raise the issue of a possible trade off between traditional values of objectivity and authenticity. PMID- 7995807 TI - Physician usage of the computer to access a hospital information system. AB - This retrospective descriptive study was undertaken to determine the characteristics of physicians who use the computer to access a Hospital Information System (HIS). A convenience sample of 630 staff physicians at a 640 bed metropolitan tertiary care teaching medical center was analyzed utilizing the variables of age, specialty, years in practice, gender, and frequency of use. A significant difference (p < or = .01) in age was found with the user physician being younger than the nonuser; no significance was found (p < or = .01) in specialty, years in practice, or gender. PMID- 7995808 TI - Serving the real need. PMID- 7995809 TI - The effect of bromocryptine-induced hypoprolactinemia on xenogeneic and allogeneic skin graft survival in a mouse model. AB - Bromocryptine-induced hypoprolactinemia produces immunosuppression capable of extending allograft survival in solid organ transplantation models, but its potential for delaying either xenogeneic or allogeneic skin graft rejection is as yet undefined. In this study the ability of bromocryptine to prolong the survival of either cutaneous human xenografts or murine allografts was compared with cyclosporin A in a mouse model. In xenograft experiments cryopreserved human cadaver skin was grafted to B6D2F1 mice. In allograft experiments skin graft donors (A/J mice) differed genetically from recipients (Balb-C mice) at the major histocompatibility locus. In the untreated control group xenograft survival averaged 7 days and allograft survival 8 days. Xenograft rejection was delayed significantly and nearly equally by both bromocryptine and cyclosporin A (mean 15 and 16 days, respectively). However, allograft rejection was delayed longer by cyclosporin A (mean 24 days; p = 0.0002) than by bromocryptine (mean 15 days; p = 0.066). Administration of porcine prolactin (1 mg) partially reversed the bromocryptine effect (mean xenograft survival, 11 days; mean allograft survival, 10 days). The results of this study suggest that the immunosuppression of prolactin release by bromocryptine may be an effective, benign means of prolonging the survival of biologic dressings (e.g., banked cadaver allograft or porcine xenograft) used for temporary wound coverage in massively burned patients. PMID- 7995810 TI - Cardiac abnormalities in children with burns: an autopsy analysis. AB - After observing several cases of endocarditis-related deaths, we determined the contribution of cardiac abnormalities to burn mortality. Autopsy reports of all burn-related deaths between 1964 and 1992 (n = 212) were reviewed for cardiac disease. Cardiac abnormalities were categorized into infectious, acquired, or congenital. Cardiac abnormalities of all forms were associated with longer hospitalizations before death and affected a larger proportion of females than expected in the male-dominated burn population. The highest incidence of endocarditis (17.3% of all deaths) occurred in the past 5 years. The frequency of other forms of cardiac abnormalities has not changed over time. Improved burn management has resulted not only in improved survival but has also prolonged the duration of hospitalization of those patients who ultimately die of their injuries. As patients are kept alive for longer periods, the incidence of endocarditis and the cardiac manifestations of multiple organ failure have increased. PMID- 7995811 TI - Influence of head and neck position on endotracheal tube tip position on chest x ray examination: a potential problem in the infant undergoing intubation. AB - Complications related to endotracheal tubes are frequent in small children and infants. We report a case of a burned 12-month-old child in whom frequent manipulation of the endotracheal tube was required because of recurrent atelectasis and changing position of the endotracheal tube on chest x-ray film. It was then determined that because of variations in head and neck position while chest x-ray films were obtained, the endotracheal tip changed position in the trachea greater than 2.7 cm (greater than 1 inch), although endotracheal tube position was maintained at the level of the teeth. Airway care and gas exchange were subsequently improved by ensuring that patient care and chest x-ray films were performed with the head and neck in similar (neck slightly flexed, head neutral) position. PMID- 7995812 TI - Management of pediatric facial burns. AB - The acute management of pediatric facial burns is not uniform. Many surgeons prefer to wait until primary wound separation occurs before grafting. Concerns over early excision are accentuated in small pediatric patients. The possible benefits of early excision results have led to adoption of this technique at our facility. This study presents our recent experience with early excision and grafting. Sixty-six patients with a mean age of 6.2 years underwent early excision and grafting of facial burns. Patients underwent grafting a mean 12.7 days after burn. Procedures were done in two stages. All grafts were dressed open. There were no episodes of acute airway decompensation. No patient required regrafting. Patients wore pressure masks a mean of 15.5 months after grafting. Thirteen patients had releases (10 eyelids, three lips/commissures) in the first postoperative year. These results demonstrate that early excision and grafting of facial burns can be carried out safely in pediatric patients with burns. The benefits of early wound coverage can thus be applied to facial burns in this population of patients. PMID- 7995813 TI - A comparison of psychologic functioning in children and adolescents with severe burns on the Rorschach and the Child Behavior Checklist. AB - The incidence of psychologic problems in 12 children and adolescents with severe burns was examined through four similar scales on the Children's Behavior Checklist and the Rorschach. No correlations were found for any of the pairs, which were Withdrawn-Isolation Index, Somatic Complaints-Anatomy + X-ray, Anxious/Depressed-Depression Index, and Thought Disorder-Schizophrenic Index. Discrepancies were explained as both accurate reflections of patients' personalities and function of the type of assessment instrument used to determine psychologic problems. Although the statistical power of the study is limited by the small sample size, the results suggest the lack of good objective psychologic assessment tools available to this population and the need for experienced professionals to interpret test results in light of their personal knowledge of the patient. PMID- 7995815 TI - Psychological distress among survivors of burn injury: the role of outcome expectations and perceptions of importance. AB - This study examined factors associated with psychologic distress among survivors of burn injury. The study tested hypotheses derived from Scheier and Carver's model of behavioral self-regulation and focused on two primary predictor variables: expectations concerning rehabilitative outcomes and the importance attached to those outcomes. The study used a cross-sectional research design. Two hundred sixteen people who had sustained major or moderate thermal burn injuries within 2 years of study entry served as subjects. Data were collected via mailed questionnaire and chart review. Consistent with study hypotheses, we found that participants who had low expectations for further improvement but who attached high importance to the need for improvement exhibited the most psychologic distress. Study findings lend support to Scheier and Carver's model and suggest that application of this model within the context of burn rehabilitation may increase our understanding of the rehabilitation process. Directions for future theory-based research are discussed. PMID- 7995814 TI - A prospective study of burn scar maturation in pediatrics: does age matter? AB - A prospective study was performed to determine whether patterns of burn scar maturation varied among different pediatric age groups. Patients were divided into three groups according to age at the time of burn injury: birth to 3 years, 4 to 11 years, and 12 to 18 years. Scarring of sheet grafts on an extremity was assessed throughout the maturation process in three areas: vascularity, pliability, and height. A 1-inch square was selected on the graft edge adjacent to unburned skin. Two experienced therapists independently evaluated the test area and averaged their scores. There were no significant differences in rate of scar maturation between age groups. Burn scar maturation of sheet skin grafts in the pediatric patient with burns demonstrated a rapid peak of scarring (1 to 2 months) and scar maturation (9 to 13 months). PMID- 7995817 TI - Simple method of applying pressure to skin grafts of neck with foam dressing and staples. AB - Pressure applied over a skin graft prevents formation of hematoma and shearing of the graft. Most of the methods used to obtain adequate pressure are often cumbersome to apply and time-consuming. This report describes a quick and simple method for fixing and applying pressure over skin graft with foam dressing and staples. PMID- 7995816 TI - Current trends in the use of allograft skin for patients with burns and reflections on the future of skin banking in the United States. AB - Cadaveric allograft skin can play a critical role in the care of patients with massive burns. It is difficult, however, to estimate current use and levels of enthusiasm for allograft skin in the United States. We report on a survey of 40 skin banks and 140 United States burn center medical directors as listed in the American Burn Association's Directory of Burn Care Resources for North America 1991-1992. Response rate was 45% for skin banks and 38% for burn directors. Overall, 12% of admitted patients were treated with allograft skin at the responding burn centers. Sixty-nine percent of burn center directors preferred to use fresh skin, although only 47% of skin banks were able to supply fresh cadaver skin. Tabulated survey results and a review and discussion of future directions in skin banking and replacement research are discussed in this paper and were presented to the Tissue Bank Special Interest group at the 1993 American Burn Association annual meeting. PMID- 7995818 TI - Photographing the patient with burns for medical documentation. AB - Photographs of a burn injury provide an objective description of the patient's disease course and may be important in the medicolegal documentation of child abuse or other criminal and civil actions. Accurate and reproducible photographs require careful composition and choice of equipment. Standardized clinical positioning is described with recommendations for timing of serial photographs. PMID- 7995819 TI - Modified Stryker frame for intraoperative positioning of the patient with burns. AB - Positioning large patients with burns for prone burn procedures can be very difficult, requiring operating room personnel to use a gang-lift technique. We have used the upper portion of a Stryker frame mounted to a standard operating room table base in more than 200 burn procedures in adults to move patients from the supine to the prone position, and back, without complication. PMID- 7995820 TI - Adaptive air travel transportation systems for persons with disabilities. AB - The Air Carrier Access Act ensures that no air carrier may discriminate against persons with disabilities. This Act specifies rules and regulations that remove architectural barriers to persons with disabilities. Other important considerations in the comprehensive adaptive air travel system for persons with disabilities include (1) aircraft boarding environment, (2) boarding chairs, (3) collapsible aircraft wheelchairs, (4) aircraft stowage procedures for battery powered wheelchairs, and (5) airport shuttle bus or van service. Educational curricula must be developed that describe the comprehensive operation of this system. Evaluation of the performance of the system for persons with disabilities is mandatory to ensure that persons with disabilities have the same level of services as those without disabilities. PMID- 7995821 TI - Burns in men secondary to spouse abuse. AB - A retrospective study of adult patients admitted to the burn center identified 61 male patients who claimed their injury to be secondary to spouse abuse. This may not be a true prevalence, because there may be many more unidentified cases. Few data are available concerning male spouse abuse in literature. Increased awareness is necessary to identify these patients for adequate psychosocial rehabilitation and to prevent a second injury. PMID- 7995822 TI - Resiliency characteristics and Rorschach variables in children and adolescents with severe burns. AB - Three raters classified 40 children and adolescents (ages 8 to 19 years) with severe burns who were placed in two groups designated as Resilient (N = 28) and Nonresilient (N = 12). Nine hypothesized differences in Rorschach responding between groups were developed through a review of the literature and operationalized through descriptive statements from a rating scale now being developed. The Resilient group gave more Cooperative Movement responses than the Nonresilient group (p = 0.0270), and they were more likely to have D scores that were within the normal range (p = 0.0700). The Nonresilient group had lower Egocentricity Index scores than the Resilient group (p = 0.0368) and more often had a positive Coping Deficit Index (p = 0.1285). Texture, Diffuse Shading, and Passive: Active responses appeared similar between groups. Differences found concerning Experience Actual and Z frequency were not statistically significant. Possible interventions addressing the emotional needs of burned children and adolescents such as strengthening certain personality characteristics are noted. PMID- 7995823 TI - Allowing severely burned patients to make the choice to die is not unique. PMID- 7995824 TI - Omiderm as an initial burn dressing. PMID- 7995825 TI - Current results of coronary bypass surgery after failed angioplasty. AB - Percutaneous Transluminal Coronary Angioplasty (PTCA) is a technique in continuous development. Since its introduction indications, number, quality of stenosis amenable to treatment and device employed have evolved leading to a change in the population undergoing treatment. Therefore surgical results obtained in the early 80's may not apply to the beginning of the 90's. This reason prompted us to review our recent experience. In the last 4 years (1989 1992) among 2563 PTCA procedures performed in our Institution, 114 patients (4.3%, CL 3.5%-5%) underwent urgent surgical revascularization because of failed angioplasty. Thirty-four patients (30%, CL 21%-38%) were older than 65 years; 68 patients (60%, CL 50%-68%) had multiple vessel disease; 63 patients (55%, CL 46% 64%) had previous Myocardial Infarction (M.I.); 20 patients (17%, CL 10%-24%) had already undergone a PTCA and 3 patients (2%, CL 0%-6%) had had coronary surgery. In 21 patients (18%, CL 11%-25%) the left ventricular Ejection Fraction (EF%) was below < 50%. Complete revascularization was always performed with an average of 2.2 +/- 1 graft/patient. A Left Internal Mammary Artery (LIMA) was implanted in 20 patients (17%, CL 10%-25%) of the patients and in 52% of cases requiring LAD grafts in the last two years. There were 2 deaths (1.7%, CL 0%-4%), both patients were in cardiac arrest before surgery (p < 0.001), 2 patients required a LVAD to be weaned from ECC and 7 patients (6%, CL 1%-10%) had an IABP inserted at the moment of surgery. Twenty-five patients (21%, CL 14%-29%) showed evidence of a new myocardial infarction.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7995826 TI - Recurrent ischemic heart disease: the effect of advancing age. AB - Four thousand four hundred and thirty open heart operations were performed at Mercy Hospital of Pittsburgh from January 1, 1988, to June 30, 1992. During that period, 168 patients were evaluated for recurrent ischemic heart disease after prior coronary artery revascularization. Forty-four were treated non operatively, the mode of therapy being transluminal angioplasty or medical management. The remaining 124 patients underwent repeat coronary revascularization. An attempt was made to define the impact of advancing age on the magnitude of risk factors, morbidity, and mortality. Advancing age is not a contraindication to repeat coronary artery revascularization. The average interval between the initial operation and the need for repeat revascularization is eight years. Younger patients have progression of their coronary artery disease, but progression of the arteriosclerotic process is in their extracranial cerebral arteries, renal arteries, and aortic segments as well as the coronary arteries. The utilization of tobacco, recent myocardial infarction, diabetes mellitus, and elevation of cholesterol are strong indicators for recurrent disease and add to the risk of repeat surgical intervention. PMID- 7995827 TI - Results of heart transplantation by extending recipient selection criteria. AB - From November 1985 to July 1993, 29 out of 241 patients (12%) who underwent heart transplantation (HTx) at our institution had one or more "classical" contraindications to HTx: age > or = 60 years (20 patients); insulin-dependent diabetes mellitus (5 patients); irreversible renal failure requiring combined heart-kidney transplantation (2 patients); previous surgery for malignancy (1 patient); familial hypercholesterolemia (1 patient) and active systemic infection (1 patient). The main indication for HTx was ischemic cardiomyopathy (21 patients, 61%). Immunosuppression regimen consisted of Cyclosporine and Azathioprine, oral prednisone being subsequently added in 6 patients because of persistent rejection. There were 2 perioperative deaths and one late death. Follow-up ranged from 1 to 88 months (mean, 28 +/- 20) with an actuarial survival at 5 years of 85 +/- 8%. Annual cardiac catheterization demonstrated normal graft function and coronary arteries in all. No significant differences in survival, incidence of rejection and infection, renal function and duration of hospitalization were found when these patients were compared with those with no contraindications to HTx. In conclusion, HTx can be performed with good early clinical results in selected patients with "classical" contraindications to HTx; longer follow-up, however, is needed to confirm whether extension of the recipient selection criteria justified. PMID- 7995829 TI - A new approach to aortic annulus enlargement. AB - Enlargement of the aortic annulus has always been a dilemma. Many techniques have been suggested. We present a new technique which was carried out on 43 patients which caused symptomatic improvement in those patients. The technique includes incising the aortic annulus at both ends of the left coronary cusp or both sides of the left coronary ostium of equal distance. Prosthetic or pericardial patches are used for enlargement. We have had good results with this technique and we believe it is an excellent alternative to prevent late complications on mitral valve. PMID- 7995828 TI - Triiodothyronine administration in coronary artery bypass surgery: effect on hemodynamics. AB - OBJECTIVE: The purpose of this study was to investigate any potential hemodynamic effect of intravenously administered triiodothyronine in patients undergoing coronary artery bypass surgery. EXPERIMENTAL DESIGN: Thirty patients were randomized in this single-blind, placebo-controlled trial. Hemodynamic parameters including heart rate, stroke volume index, cardiac index, pulmonary wedge pressure, pulmonary vascular resistances, systemic vascular resistances, and mean blood pressure, were compared between the two groups preoperatively, before the initiation of cardiopulmonary bypass (CPB), 5 minutes after the end of CPB, and 2, 4, 10, 16, and 22 hours thereafter. INTERVENTION: Triiodothyronine was administered as a bolus infusion over a 1 min period after removal of the aortic cross-clamp, (0.15 microgram/kg), before the end of CPB (0.1 microgram/kg), 4 hours after the end of CPB (0.1 microgram/kg), 9 hours after CPB (0.1 microgram/kg), and 14 hours after CPB (0.1 microgram/kg). Patients received inotropes, vasodilators, and diuretics only if specifically indicated. RESULTS: Plasma FT3 levels were higher in the T3 group, but within the normal range. No significant differences were noted in the pre and post CPB hemodynamics between the two groups for the most part of the study except that heart rate was increased in T3 group. A greater number of patients in the control group received vasodilators. No adverse reactions were noted with triiodothyronine administration. CONCLUSION: Triiodothyronine administration in patients undergoing cardiopulmonary bypass surgery is safe, may lessen the need for pharmacological (vasodilator) therapy, but may increase heart rate. PMID- 7995831 TI - Aortic dissection as complication of supravalvular aortic stenosis. AB - A 2-year-old patient with diffuse supravalvular aortic stenosis and the Williams Beuren syndrome at autopsy was found to have dissection of the ascending aorta in addition to severe coronary artery disease and microfocal myocardial fibrosis. These findings emphasize the need for early surgical intervention in supravalvular aortic stenosis. PMID- 7995830 TI - Homograft aortic root replacement for destructive valve endocarditis. The benefit of an in-house homograft bank. AB - This report concerns the surgical treatment of a 45-year old patient with active staphylococcus-endocarditis of the aortic valve which resulted in an aortic root abscess and consequently in a ventricular aortic discontinuity. A technique of homograft aortic root replacement after removal of all infected and necrotic areas is described. After a six month follow-up, the patient is asymptomatic (New York Heart Association functional class I) and shows no signs of recurrence of endocarditis. This case report makes the benefit of an in-house homograft-bank system obvious. PMID- 7995832 TI - Current applications of duplex ultrasonography and color Doppler imaging. AB - Duplex ultrasound is a noninvasive method of evaluating the function of the systemic arteries and veins. In this review, the physical principles of duplex ultrasonography are discussed and compared to other available noninvasive tests. The clinical applications of duplex ultrasound and color Doppler imaging are reviewed and diagnostic criteria stated. Newer and more controversial applications of duplex ultrasound are presented. PMID- 7995833 TI - The morphology of the carotid artery after uncomplicated endarterectomy. AB - Endarterectomy of the carotid sinus is one of the most frequent vascular operations. Until now, however, few details have been reported on the characteristic features of the disobliteration site during uncomplicated postoperative progress. Full histological and morphometric investigation was performed on the bifurcation of the carotid artery of 23 autopsies with previous endarterectomy, in some cases on both sides. The postoperative interval was of up to 10 years duration (early phase up to 6 months postoperatively 15x, late phase 14x). The findings were compared with surgical specimens of 9 restenoses. The reconstruction of an inner layer (so-called neointima) and the smoothing of the marginal layers of the disobliteration site takes place rapidly through the proliferation of smooth muscle cells from the remaining portions of the media. The narrower this remaining portion of the media, the greater the width achieved by these "neo-intima" (p < 0.05). There is occasional formation of elastic lamellae, similar to an elastic internal lamina, close to the luminal surface. Furthermore, in some cases the reconstruction of an intimal thickening (fibrous ridge) characteristic of the carotid bifurcation was observed at the entrance to the carotid sinus; this can be assessed as an indication that flow irregularities apparently persist postoperatively at this location. In the late phase, intramural calcification and new sclerotic plaques usually occur; these plaques closely resemble those of surgically removed restenoses. The distribution of plaques of this kind is largely congruent with the pattern of plaques in asymptomatically diseased carotid arteries. Thus, following endarterectomy in the carotid sinus, sclerotic plaques recur even during an uncomplicated course subsequent to reparative processes; as with the natural history of sclerotic plaques at the carotid bifurcation, this recurrence seems to be largely determined by hemodynamic factors. PMID- 7995834 TI - Distal bypass for limb salvage: comparative study in patients below and above 80 years of age. AB - Revascularization for chronic lower extremity ischemia in patients of 80 years and older is controversial. To better define operative risk and outcome after peripheral vascular procedures in the elderly, our experience from January 1990 to December 1992 was reviewed. We compared two groups of patients: group I with 26 patients (28 revascularizations) 80 years of age and older (84 +/- 3 years) and group II with 29 patients (32 revascularizations) younger than 80 years (70 +/- 8 year). The two groups were similar with regard to risk factors, surgical indication (rest pain and/or gangrene) and type of graft (in situ vein: 35, reversed vein: 12, PTFE: 13). Fourteen femoro-popliteal bypasses, 17 femoro tibial bypasses (8 to the anterior tibial artery and 9 to the posterior tibial artery) and 29 femoro-peroneal bypasses were performed. The operative mortality rate was 11.5% in group I and 6.9% in group II. The cumulative life-table survival rate at 24 months was 39.5% in group I and 55% in group II. Primary patency rate at 24 months was 64% in group I and 67% in group II. Secondary patency rate at 24 months was 74.5% in group I and 73% in group II. Limb salvage at 24 months was 80% in group I and 83% in group II. Comparison of the older and younger groups showed no statistically significant difference in mortality rate, graft patency and limb salvage. Operative mortality and graft patency were not different with regard to age of patients. PMID- 7995835 TI - Endothelial cell seeded dacron aortobifurcated grafts: platelet deposition and long-term follow-up. AB - OBJECTIVE: The prospect of seeding endothelial cells to a prosthetic graft has been successful in the experimental setting, but less convincing in clinical studies in humans. This study was performed with the objective of evaluating endothelial cell seeding of aorto-bi-iliofemoral reconstructions with cells harvested at the same procedure. EXPERIMENTAL DESIGN: Randomized study with one graft limb seeded and with at least 5 year follow-up. SETTING: University Hospital. PATIENTS: 15 patients undergoing aorto-bi-ilio-femoral reconstruction. INTERVENTIONS: One graft limb (randomly determined) was seeded with autologous endothelial cells (median 5.2 x 10(5)) enzymatically (Dispase II) harvested from the saphenous vein (length 8-15 cm, diameter 4-8 mm). The other graft limb served as a control. MEASURES: Two months after surgery platelets were labelled with 111In and platelet activity registered over the graft. Long-term outcome were followed (median 5 years and 10 months). RESULTS: No difference in platelet activity was noted between the seeded and non-seeded graft limb. Different techniques of calculating graft wall activity showed large interindividual variations in the results. Long-term outcome showed that three patients died, two from myocardial infarction on postoperative day three and 60, and one patient died four years after surgery from a lung cancer. Grafts functioned well. In one non-seeded graft limb the patient had severe microembolisation postoperatively that required amputation 10 days after surgery. Of seeded graft limbs one occluded 42 months after surgery, intimal hyperplasia at the distal anastomosis was seen and in one patient progress of arteriosclerosis required additional surgery 12 months after initial operation with profundaplasty (partly due to intimal hyperplasia) and later two additional femoro-distal reconstructions were needed. CONCLUSION: In summary with our single-staged technique for seeding of endothelial cells to a graft limb in a high flow situation no effect on platelet activity at two months was found and long-term outcome was not obviously influenced. PMID- 7995836 TI - Ischemia-reperfusion syndrome: an alternative experimental model. AB - OBJECTIVE: To design an alternative experimental model of ischemia-reperfusion syndrome. Our model mimics the clinical pattern of the syndrome and also assesses the efficacy of therapeutical protocols. EXPERIMENTAL DESIGN: Ischemia was induced under general anaesthesia in the posterior limbs of 10 sheep by occluding the aorta and vena cava by means of two-way balloon catheters. Ischemia was stopped after 4 hours and blood and histologic parameters determined in the first three hours of revascularization. The animals were divided into three groups: a group of 3 sheep in which a sham operation was performed; a control group (5) to assess the efficacy of induced ischemia; the third group (5) to determine the effect of antioxidant and membrane protective drugs to assess the reliability of the model to study the ischemia-reperfusion syndrome. RESULTS: At the end of ischemia, skin temperature was decreased (p < 0.04) both in control and treated groups, pH decreased significantly soon after reperfusion in the control group (p < 0.04). Reperfusion in control sheep, compared with treated animals, was followed by a significant increase in CPK blood levels (p < 0.009), related to marked muscle damage, in particular after reperfusion. Tissue damage detected at TEM was less severe in treated animals. CONCLUSIONS: This model is an effective experimental strategy and a means of assessing preventive treatment. PMID- 7995837 TI - Case report on primary and secondary aortoenteric fistula in patient. AB - A rare case is reported of a 77-year-old male with secondary aortoenteric fistula after earlier ligation of infrarenal aorta without any prosthetic grafting in the abdomen. The patient was admitted into our Clinic suffering from haematemesis and melaena. The combination of our patient's medical history, the endoscopic picture and MRI arteriography indicated the likelihood of a secondary aortoenteric fistula. Three years before this our patient had been successfully operated on for a primary aortoenteric fistula having an aneurysmectomy, ligation of the infrarenal aorta and an axillobifemoral bypass performed on him while the duodenum was sutured and patched with omentum. The choice of this surgical procedure was unavoidable because our patient had been operated on for a duodenal ulcer perforation 3 days before this. With the diagnosis of a secondary aortoenteric fistula very possible an urgent laparotomy was performed revealing a fistula between the third duodenal portion and the aortic stump. The duodenum was separated from the aortic stump to which a dacron patch, posterior peritoneum and omentum were sewn. Postoperatively the patient required respiratory support in intensive care for 4 days and was discharged within 8 days. Today, two years later, he continues to be in excellent condition. PMID- 7995838 TI - Renal artery stenosis in moyamoya syndrome. AB - Extracranial manifestations of vascular occlusive disease, such as renovascular hypertension, are rare in moyamoya syndrome. Histopathological examination suggests a common denominator. Surgical or endoluminal correction of these lesions is feasible. Moyamoya syndrome is not considered to be a contraindication for organ donation for transplantation. PMID- 7995839 TI - Videothoracoscopy and video-assisted small thoracotomy for the treatment of pulmonary malignancies. AB - Video-assisted thoracic surgical procedures continue to be performed with increased frequency; the role of this new technique in the treatment of pulmonary malignancies or metastatic mediastinal adenopathies is not yet defined. Out of a series of 100 consecutive video-assisted thoracic operations, 22 patients resulted affected by a malignancy in the lung or in the subcarinal lymphnodes: six patients had a primary lung cancer and were operated with a video-assisted small thoracotomy of 5 cm (three lobectomy and three segmentectomy) because of a very poor respiratory reserve. Nine patients received a video-assisted wedge resection of a nodule resulted at the frozen section a metastasis of a carcinoma: a small thoracotomy of 8 cm was made and a hand entered the thoracic cage to obtain a careful palpation of the entire lung; five patients had enlarged lymphnodes only in posterior and inferior mediastinum, inaccessible by cervical mediastinoscopy or anterior mediastinotomy: thoracoscopic exploration obtained a useful mediastinal nodal sampling for these adenopathies. In selected cases video assisted thoracic surgery can be used for resection or assessment of thoracic malignancies. PMID- 7995840 TI - Management of postpneumonectomy bronchopleural fistulae. A review. AB - The management of postpneumonectomy bronchopleural fistulae continues to constitute a major therapeutic challenge. Refinements of surgical techniques have reduced the incidence of this dreaded complication although it cannot be totally prevented. Management remains controversial. We report our recent experience of three patients with bronchopleural fistulae following a right pneumonectomy, two for bronchogenic carcinoma and another for non-tuberculous, suppurative lung disease. Our treatment of choice for these patients is, immediate pleural drainage together with parenteral broad spectrum antibiotics followed by endoscopic closure of the fistula with monomeric n-butyl-2-cyanoacrylate glue (Histoacryl blue, B Braun, Melsungen, Germany). The pleural space is then irrigated with Povidone Iodine to sterility following which the closed bronchial stump is reinforced following which the closed bronchial stump is reinforced and the pleural space obliterated by decortication, omentopexy and by a tailored thoracoplasty. This cosmetically acceptable treatment produces minimal functional disability and is achieved with minimal morbidity and mortality in these critically ill patients. PMID- 7995841 TI - Separation of thoracopagus conjoined twins. A case report. AB - A pair of thoracopagus conjoined twins with a connection at the atrioventricular groove of both hearts and a huge conjoined liver were surgically separated. An aortopulmonary shunt was created for Twin B, a victim of complex congenital heart disease with hypoplastic right heart syndrome, who died 5 hours later. However, Twin A survived after prolonged endotracheal intubation and parenteral nutrition. He survived for 7 months, and went home, but finally died of sepsis. In reviewing 47 pairs of surgically separated thoracopagus conjoined twins, in 30 pairs of type A (Leachman's classification, completely separate hearts), 42 patients survived (70%); in 5 pairs of type B (atrial connection only), one patient survived (10%); in 9 pairs of type C (both atrial and ventricular interconnections), none survived; in 3 pairs of unknown type, 2 survived. Total survival rate of surgically separated thoracopagus conjoined twins was 47.9%. The survival rate was 38.2% in those operated in the neonatal period (n = 34) and 63.6% in those operated over 1 month of age (n = 44) (p = 0.016). In conclusion, thoracopagus conjoined twins are rare. Although its separation carries a high risk, especially in those with cardiac connection, this report confirmed that separation is still feasible under proper preparation and planning. PMID- 7995842 TI - Executive function abilities in autism and Tourette syndrome: an information processing approach. AB - This study used information processing paradigms to provide a detailed examination of executive function abilities in autism. The performance of non retarded autistic children was compared with that of two matched control groups, one with Tourette Syndrome and the other developmentally normal. Autistic subjects performed as well as controls on tasks requiring global-local processing and inhibition of neutral responses. In contrast to both control groups, however, the autistic sample was significantly impaired on a measure of cognitive flexibility. The performance of children with Tourette Syndrome did not differ from that of normal controls on any task. These results refine our knowledge about executive dysfunction in autism and suggest a new conceptual framework and general method for investigating the cognitive underpinnings of neurodevelopmental disorders. PMID- 7995844 TI - Predicting and explaining behavior: a comparison of autistic, mentally retarded and normal children. AB - The relationship between performance on a false belief task and a new task designed to elicit explanations of human action was examined in two experiments. In the first study normal preschoolers' performance on both tasks was significantly correlated. The second experiment included matched groups of autistic, mentally retarded, and older normal children. The autistic subjects were significantly worse than controls at offering mentalistic explanations. Performance on the false belief and the explanation of action tasks was highly correlated for the autistic subjects. These findings are discussed in terms of the relationships between language and theory of mind. PMID- 7995845 TI - The effects of parental separation, the timing of separation and gender on children's performance on cognitive tests. AB - The relationship between exposure to parental separation and measures of cognitive ability and school achievement was examined in a birth cohort of New Zealand children studied to the age of 13 years. Children who were exposed to parental separation following the point of school entry had mean test scores that were between .1 and .3 standard deviations lower than children who had not been exposed to separation even when due allowance was made for potentially confounding variables. Separation prior to school entry was found to be unrelated to later outcomes after adjustment for confounding factors. There was no evidence to suggest that the effects of separation varied with the child's gender. The association between parental separation after school entry and cognitive test scores was similar for children whose custodial parents remarried and those who did not remarry. PMID- 7995843 TI - Face perception in children with autism and Asperger's syndrome. AB - Children with diagnoses of either autism or Asperger's syndrome were matched on measures of verbal mental age with nonautistic control children. They were tested on their abilities to process both facial and nonfacial stimuli. There were no significant differences between the low ability autistic and control groups, but the high ability autistic and Asperger's children performed significantly worse than controls across all tests. Group averages masked substantial individual variation. The results are seen as indicating a general perceptual deficit that is not specific to faces or emotions. This appears to be a common correlate of autism and Asperger's syndrome, rather than a core symptom. PMID- 7995846 TI - Chronic family adversity and early child behavior problems: a longitudinal study of low income families. AB - A beginning step in the prevention of child psychopathology is the identification of conditions associated with a disproportionately high incidence of behavior problems. Rutter and colleagues (British Journal of Psychiatry, 1975, 126, 493 509) have reported a dramatic increase in the probability of child adjustment difficulties as a function of multiple family stressors. However, few investigators have tested this association beginning in infancy. The present investigation examines this relationship at the ages of 1 and 2 with behavioral adjustment at age 3 among 100 low-income families. Broad support was found for the family adversity hypothesis, though sex differences were evident regarding individual correlates of problem behavior. PMID- 7995847 TI - The childhoods of multiple problem adolescents: a 15-year longitudinal study. AB - This paper examines the life history of a small group of adolescents (3%) who were identified during the course of a longitudinal study of a birth cohort of New Zealand children as displaying multiple problem behaviours at the age of 15 years. This group was characterised by conduct disorder, police contact, substance abuse behaviours, early onset sexual activity, suicidal ideation, mood disorders and lowered self esteem. Statistical biographies of this group of young people showed that many were the offspring of seriously disadvantaged, dysfunctional and disorganised home environments. The implications of these findings for the understanding and treatment of multiple problem behaviours in adolescence are discussed. PMID- 7995848 TI - Comorbidity of empirically based syndromes in matched general population and clinical samples. AB - Comorbidity of deviance on eight empirically based syndromes was compared in matched general population and clinical samples of 2,705 children aged 4-18, using a bidirectional formula to avoid confounding effects of differential base rates. Syndromes were assessed via parent ratings on the CBCL, teacher ratings on the TRF, and self ratings on the YSR. Significantly higher comorbidity rates were obtained for clinical than general population samples for all 28 pairings of CBCL syndromes, 15 pairings of TRF syndromes, and 22 pairings of YSR syndromes. Bidirectional comorbidity rates for empirically based syndromes were compared to pairings of comparable DSM-III diagnoses. PMID- 7995849 TI - Annotation: sociometry and peer relationships. PMID- 7995850 TI - The influence of topic and listener familiarity on aphasic discourse. AB - This study investigated the effects of listener and topic familiarity on verbal output. A total of 32 subjects were included: 5 Broca's, 7 conduction, and 10 anomic aphasics; and 10 normal controls. Subjects performed story retell and procedural discourse tasks containing familiar and unfamiliar topics. Tasks were completed with a familiar listener (spouse) and an unfamiliar listener (examiner). Results indicated that topic familiarity significantly influenced verbal output, however specific findings were dependent on task. In procedural discourse, the amount of verbal output (number of T-units) was significantly greater on familiar topics. In contrast, the complexity (number of words and clauses per T-unit) was significantly greater on unfamiliar topics. On story retell, verbal output (number of T-units) was also greater on familiar topics. However, grammatic complexity did not increase with unfamiliar topics. Words per T-unit remained higher on familiar topics. The variable of listener familiarity was not found to be significant. PMID- 7995851 TI - Word skills of children normal and impaired in communication skills and measures of language and speech development. AB - Results from two related investigations are reported, one using 60 normal language learners, ages 3-5 and one using 34 children with communication disorders, ages 5.4-8.5. Tasks involving the sequential recall of words from five categories (nouns, verbs, adjectives, adverbs, and prepositions) were given to the subjects in each investigation, thus providing an opportunity to compare group performances. A hierarchy of recall strengths of words from different categories and the organizational pattern of scores was determined for each group. Each group's word category scores were used as independent variables in regression analyses to predict scores from a battery of language tests and a test of phonology. The results were anticipated to be capable of contributing to descriptions of children's mental dictionaries, have implications for word category differences in normal and impaired language learners, and clinical relevance. Comparisons of the word recall accuracy of skills of children from each group revealed that the younger normal Ss had word scores equal to the older language and speech impaired children. However, the hierarchy of word category strengths and the patterns of organization within each group's mental dictionary were essentially the same in both groups. Word category scores predicted language and speech scores in both investigations, but the prediction was stronger in the children having impaired language or speech. PMID- 7995852 TI - Follow-up of children at risk for language problems. AB - Nineteen students (ages 10-14) who were previously identified as at risk for language problems were examined after a period of five to seven years. Information concerning cognitive, academic, and linguistic skills was collected using standardized and informal measures. Results were analyzed for the total group and also for two subgroups. At the time of follow-up, seven subjects (37%) who had not been served by a speech-language pathologist (SLP) were unidentified with language impairments (LI); two subjects (11%) were being seen by a SLP; one subject (5%) was identified as mentally handicapped, and nine subjects (47%) did not exhibit language problems. Subgroup comparisons between the seven unidentified language impaired subjects (LI) and the nine without language impairments (contrast = CG) revealed lower language scores, especially for receptive and composite language as measured by the CELF-R and TLC-E. Teachers rated these two groups (LI and CG) differently in the areas of following/giving directions, initiating/maintaining conversation, and taking turns. Parents also reported greater concerns for the LI group in the areas of listening, communication, and social skills. Issues concerning identification of at-risk groups and future studies using at-risk populations are discussed. PMID- 7995853 TI - Effects of vocal loudness on nasalance measures. AB - The effects of vocal loudness on measures of nasalance was evaluated. Subjects were 30 young adult females with no history of communication disorder who spoke two stimulus passages at three levels of vocal loudness. One passage contained no nasal consonants (Zoo Passage) and the other contained about 35% nasal consonants (Nasal Sentences). The results indicate that there was no significant difference in nasalance measures across the three levels of vocal loudness for either passage. However, when the nasalance measures for the three conditions of vocal loudness were ranked from low to high for each subject, there was an interesting tendency for a subject's lowest nasalance score to occur in the loudest vocal condition on the Nasal Sentences but not for the non-nasal speech material of the Zoo Passage. The implications of these findings with regard to velopharyngeal function are discussed. PMID- 7995854 TI - Neurochemical compartmentalization of the globus pallidus in the rat: an immunocytochemical study of calcium-binding proteins. AB - The globus pallidus external segment forms a major target center of the mammalian striatum which is characterized by neurochemically distinct compartments. The present study was undertaken to determine if a corresponding compartmentalization exists within the globus pallidus external segment in the rat. Immunocytochemical examination of the calcium-binding proteins parvalbumin and calbindin D28kDa, which are present in neurons of the striatal matrix compartment, was employed. The results indicate three neurochemically distinct compartments within the globus pallidus external segment: 1) an area in the medial aspect of the entire length of the globus pallidus that contains dense immunoreactivity for calbindin D28kDa; 2) a narrow rim at the striatopallidal junction in the rostral two-thirds of the globus palidus that contains calbindin D28kDa immunoreactivity designated as the "border zone" of the globus pallidus; and 3) an area between these two zones showing very poor immunoreactivity for calbindin D28kDa but containing parvalbumin immunoreactive neurons. The calbindin D28kDa immunoreactive border zone corresponds to the area of the globus pallidus where striatal inputs converge extensively, whereas the rest of the nucleus is involved in segregated, topographically organized pathways. Parvalbumin-containing neurons are involved in the propagation of striatal output related to striosomal and sensorimotor aspects of basal ganglia function. The present results also indicate that calbindin D28kDa immunoreactivity is completely absent from striosomal neurons and is therefore a useful marker for striatal compartments. PMID- 7995855 TI - Anatomical properties of brainstem trigeminal neurons that respond to electrical stimulation of dural blood vessels. AB - Single unit recording studies in anesthetized cats have identified a population of neurons in the brainstem trigeminal complex that can be activated by stimulation of major dural blood vessels. Such dura-responsive neurons exhibit response properties that are appropriate for a role in the mediation of vascular head pain in that they typically exhibit nociceptive facial receptive fields whose periorbital distribution is similar to the region of referred pain evoked by dural stimulation in humans. In the present study, intracellular labelling with horseradish peroxidase was used to examine the anatomical characteristics of brainstem trigeminal neurons that respond to dural stimulation. A total of 17 neurons was labelled that responded to electrical stimulation of dural sites overlying the superior sagittal sinus or middle meningeal artery. Fourteen of these neurons also responded to electrical stimulation of the cornea. The neurons in this sample were located in the rostral two-thirds of the trigeminal nucleus caudalis and the caudalmost part of the nucleus interpolaris. Within caudalis, the neurons were located in the deeper part of the nucleus, primarily lamina V, and were concentrated ventrolaterally. The dendritic arborizations of the dura responsive neurons typically exhibited a dorsolateral-to-ventromedial orientation and did not extend into the superficial laminae of caudalis. Dura-responsive neurons had axonal collaterals and boutons in the nucleus caudalis, nucleus interpolaris, the infratrigeminal region ventral to nucleus interpolaris, the nucleus of the solitary tract, and the medullary reticular formation. The axonal boutons within the trigeminal complex exhibited a ventrolateral distribution which largely overlapped the distribution of the somata. The results are consistent with previous evidence that dura-responsive brainstem trigeminal neurons may have a role in the mediation of dural vascular head pain and also indicate that such neurons may contribute to nociceptive processing within the dorsal horn. PMID- 7995857 TI - 24th annual meeting of the American Association for Dental Research. 19th annual meeting of the Canadian Association for Dental Research. March 8-12, 1995, San Antonio, Texas. Abstracts. PMID- 7995856 TI - Distribution of the alpha-ketoglutarate dehydrogenase complex in rat brain. AB - The alpha-ketoglutarate dehydrogenase complex (KGDHC) is a key enzyme in mitochondrial oxidation that appears critical to neurodegenerative diseases. Its activity in the brain declines in thiamine-deficient animals, Alzheimer's disease, and Wernicke-Korsakoff syndrome. Since selective cell populations are affected in these disorders, understanding the cellular distribution of KGDHC is important in order to define its role in the pathophysiology of these diseases. We used antisera against both bovine KGDHC and its E1k component to determine the immunocytochemical distribution of the enzyme and compare it with that of another mitochondrial enzyme, pyruvate dehydrogenase complex (PDHC) and a cholinergic neuronal marker, choline acetyltransferase (ChAT) in rat brain. Although low levels of immunoreactivity occurred in neurons, glia, and neuropil throughout the brain, some regions displayed relatively high perikaryal KGDHC enrichment. In the cerebral cortex, high immunoreactivity occurred mostly in layers III, V, and VI. The hippocampal pyramidal layer in CA1 and CA2 exhibited more intense staining than CA3. In the mammillary body, intensely labeled cells occurred in the supramammillary and lateral nuclei, while moderately stained cells predominated in the medial nucleus. The basal forebrain, basal ganglia, reticular and midline thalamic nuclei, red nucleus, pons, cranial nerve nuclei, inferior and superior colliculi, and cerebellar nuclei also contained highly immunoreactive neurons. The distribution of KGDHC overlapped with that of PDHC and colocalized to a limited extent with ChAT. These data are the first to demonstrate KGDHC immunoreactivity in discrete areas of rat brain and are vital to our understanding of selective vulnerability to metabolic insults and disease. PMID- 7995859 TI - Further refinement of percutaneous tracheostomy technique. PMID- 7995858 TI - Does dietary manipulation influence weaning from artificial ventilation? PMID- 7995860 TI - Tension pneumothorax. PMID- 7995861 TI - High fat, low carbohydrate, enteral feeding in patients weaning from the ventilator. AB - OBJECTIVE: To study whether high fat, low carbohydrate enteral nutrition could reduce VCO2 in patients during ventilator support and weaning from the ventilator in order to facilitate the weaning process. DESIGN: prospective, randomized controlled study. SETTING: Medical ICU of a university hospital. PATIENTS: 32 ventilator-dependent patients with a prospect of weaning from mechanical ventilation. INTERVENTIONS: high fat feeding administered to 15 patients and standard isocaloric feeding administered to 17 patients, both in a dosage of 1.5 times basal metabolic rate. MEASUREMENTS AND RESULTS: Respiratory and metabolic measurements were obtained both during mechanical ventilation and weaning procedures. High fat feeding was associated with significantly lower RQ values compared with standard feeding; the mean (+/- SEM) RQ values during mechanical ventilation amounted to 0.91 +/- 0.01 and 1.00 +/- 0.02 and during weaning to 0.72 +/- 0.02 and 0.86 +/- 0.02 for high fat and standard nutrition respectively (both p-values < 0.001). High fat feeding reduced the CO2-excretion both during mechanical ventilation and weaning, but only the decrease during weaning proved to be significant; the mean (+/- SEM) CO2-excretion amounted to 0.177 +/- 0.010 and 0.231 +/- 0.011 1/min STPD for the high fat and standard feeding respectively (p < 0.01). No significant differences were found in the PaCO2 during weaning between the two feeding groups. CONCLUSION: High fat, low carbohydrate enteral feeding significantly reduced the RQ values in ventilated patients with decreases in VCO2, but in this study failed to reduce PaCO2 during weaning from the ventilator. PMID- 7995862 TI - Bedside percutaneous dilational tracheostomy with endoscopic guidance: experience with 71 ICU patients. AB - OBJECTIVE: To assess the value of endoscopic guidance in bedside percutaneous dilational tracheostomy. DESIGN: The medical critical care unit of a large community hospital. SETTING: 71 consecutive adult patients who required prolonged mechanical ventilation. INTERVENTIONS: 72 elective percutaneous dilational tracheostomies using the Ciaglia technique were performed under view of a flexible fiberoptic bronchoscope. MEASUREMENTS AND RESULTS: Patients were examined during tracheostomy and on days 2 and 7 after the procedure, at discharge and after half a year if they were still alive. A correct median puncture was observed by endoscopic control in 59 interventions. An initial paramedian puncture was detected in 13/72 (18%) procedures and was corrected by renewed insertion in all cases. No severe complications related to percutaneous dilational tracheostomy were noticed. Minor complications occurred in 4/71 (5.6%) patients including minor bleeding in 2, inflammatory infiltration in 1 and one superficial lesion of the posterior tracheal mucosa. Long-term follow-up revealed stomal granulation in 3 patients including one at the tracheal site. At the end of the observation period the tracheostomy still was in use in 14/71 (20%) patients and 12/71 (17%) patients were decannulated. Due to their severe underlying diseases 45/71 (63%) patients had died. To facilitate weaning from the tracheostomy a minitracheostomy tube was used in 3 patients. CONCLUSION: Percutaneous dilational tracheostomy is a simple bedside procedure associated with a low complication rate. We recommend the use of endoscopic guidance to increase the safety of tracheal puncture and dilation procedure. PMID- 7995863 TI - In vitro accuracy of three blood O2 saturation optic catheter systems. AB - OBJECTIVE: The measure of the precision and accuracy of three optic SvO2 systems in vitro (SAT-2 Baxter, oximetrix 3 Abbott, HEMOPRO-2 Spectramed in a wide range of saturations (24-85%) and hematocrit (20-40%). DESIGN: In vitro comparison of the results given by a Co-Oximeter and the SvO2 systems. MEASUREMENTS AND RESULTS: 144 blood samples were tonometered with a variety of gas mixtures. Measurements of SvO2 were compared to those obtained by means of a Co-Oximeter, the difference (dSO2) between paired values were calculated. Precision was evaluated from confidence intervals (2SD) and accuracy was tested using dSO2 figures. As there was no difference in either precision or accuracy among catheters for a given system, data obtained from a given system were pooled. Mean precision was 14.2%, 8.6%, 9% for the Spectramed, Baxter and Abbott systems, respectively. CONCLUSION: The rather low reliability of the optic method should be borne in mind in patients with low SvO2 and/or low hematocrit. PMID- 7995865 TI - Hypocortisolaemia and adrenocortical responsiveness at onset of septic shock. AB - OBJECTIVE: To characterise the plasma cortisol profile and adreno-cortial responsiveness (short Synacthen test) of patients in septic shock. DESIGN: Retrospective assessment using case-notes and ICU charts. SETTING: University teaching hospital ICU. PATIENTS: 68 septic shock patients with plasma cortisol and/or short Synacthen test measured at ICU-admission or onset of shock post ICU admission. Patients were identified from a total population of 155 patients who had PCL and/or SST measured over a 4.5 year period. INTERVENTION: None. MEASUREMENTS AND RESULTS: Patients with septic shock had a plasma cortisol ranging from 210-8900 nmol/l and mortality of 56%. There were 22 (32%) below (low) and 46 (68%) above (high) a 'critical' plasma cortisol of 500 nmol/l. Using stepwise logistic regression, mortality was adequately predicted by and increased with, increasing plasma cortisol and onset of shock remote from ICU-admission. Short Synacthen tests were available in 33 patients: 11 responders (cortisol increment > 200 nmol/l above baseline 30 min after 0.25 mg intravenous Synacthen) and 22 hypo-responders. Mortality in patients was adequately predicted by and increased with a decrease in cortisol increment post-Synacthen. Thirteen patients (plasma cortisol 606 +/- [SD] 297 nmol/l) had complete haemodynamic profiles before inotropic therapy; no relationship was demonstrated between plasma cortisol and circulatory variables. Follow-up revealed no cases of Addison's disease. CONCLUSIONS: In septic shock, 'hypocortisolaemia' is not uncommon and does not predict a high mortality; adrenocortical hypo-responsiveness may be associated with poor outcome. PMID- 7995864 TI - Accuracy assessment for three fiberoptic pulmonary artery catheters for SvO2 monitoring. AB - OBJECTIVE: To compare values of SvO2 obtained by reflectance spectrophotometry continuous monitoring with those obtained from blood samples measurements by transmission spectrophotometry (Co-Oximetry). DESIGN: Values of SvO2 recorded by three pulmonary artery catheters for continuous monitoring, SAT1, SAT2 and Oximetrix3 (OX3), were compared in a prospective manner to those measured on blood samples by a Co-Oximeter, using the statistical analysis of Bland and Altman. SETTING: Adult intensive care unit in an University Hospital. PATIENTS: 37 patients admitted for acute respiratory failure and/or shock who required hemodynamic monitoring. MAIN RESULTS: The bias (average under- or overestimation) was small for all comparative measurements: +1.3, -0.2 and +1.0 sat% for SAT1, SAT2 and OX3, respectively. However, limits of agreement were only acceptable for SAT2 (-8.3 to +7.9 sat%) and OX3 (-6.7 to +8.6 sat%), but not for SAT1 (-23.3 to +25.9 sat%). No significant drift during 24 h was found with the three catheters. However, in vitro calibration was only found acceptable for SAT2 and OX3. The results were not influenced by the numbers of wavelengths of the device (2 for SAT1 and SAT2, and 3 for OX3) nor did they correlate with any of the hemodynamic and biochemical variables tested. CONCLUSION: For usual monitoring in the ICU, SAT2 and OX3, gave SvO2 values which are in acceptable agreement with SvO2 measured on blood samples by Co-Oximetry. PMID- 7995866 TI - Malassezia furfur-related colonization and infection of central venous catheters. A prospective study in a pediatric intensive care unit. AB - OBJECTIVE: To determine the incidence of Malassezia furfur-related colonization and infection of central venous catheters. DESIGN: Prospective clinical study. SETTING: A paediatric intensive care unit at a University Hospital. PATIENTS: 66 newborns with central venous catheters for parenteral nutrition including lipid emulsions (Intralipid). METHODS: When a central venous catheter was removed, it was rinsed with 1 ml of physiological saline, transported at ambient temperature to the clinical laboratory and cultured on Dixon's medium. The tip of the central venous catheter was used for a bacteriological study using Maki's technique. In case of suspected sepsis, blood cultures were obtained using an Isolator tube. RESULTS. 74 central venous catheters were included: mean duration of use of a central venous catheters and infusions of lipid emulsion (Intralipid) were 19.3 +/- 10 days and 8.6 +/- 8 days respectively. Only 2 central venous catheters (2.7%) were colonized by Malassezia furfur: (Mf) one in an asymptomatic newborn, and the other in an infected newborn with signs of sepsis, who most probably died at 4 months of age from refractory hypoxia due to pulmonary hypoplasia, but not from Mf sepsis. CONCLUSIONS: The incidence of Malassezia furfur-related colonization of central venous catheters appears to be low but not negligible, which warrants the use of specific culture techniques. PMID- 7995867 TI - Estimation of cardiac index by means of the arterial and the mixed venous oxygen content and pulmonary oxygen uptake determination in the early post-operative period following surgery of congenital heart disease. AB - OBJECTIVE: To assess the reliability of estimation of cardiac index based on the mixed venous oxygen saturation and methods of improving the estimation of cardiac index. SETTING: PICU in an university hospital. DESIGN: In the post-operative period following complete repair of congenital heart disease we carried out 55 measurements of blood gases in 25 infants and children (mean age 16.1 months, mean body surface 0.43 m2) from a systemic artery (arterial) and the pulmonary artery (mixed venous). We also determined the pulmonary oxygen uptake and calculated the cardiac index (CI) using Fick's principle. In the analysis we compared the CI with the mixed venous oxygen saturation (SvO2) and with the quotient of the arterial oxygen content (CaO2) and the oxygen extraction (Ca vDO2). This quotient is equal to arterial oxygen delivery (DO2) divided by the oxygen consumption (VO2). RESULTS: Pearson's correlation coefficient was 0.77 when SvO2 was compared to CI in a linear regression model. Assuming an inverse relationship between SvO2 and CI the correlation was much better (r = 0.90). However, the best estimation of CI provides the quotient CaO2/Ca-vDO2 (r = 0.93). CONCLUSIONS: CaO2/Ca-vDO2 correlates much better with CI than the SvO2, therefore CI could be better estimated based on CaO2/Ca-vDO2. Furthermore CaO2/Ca-vDO2 provides good information about the oxygen supply situation of the body. PMID- 7995868 TI - Outpatient therapy of iatrogenic drug dependency following prolonged sedation in the pediatric intensive care unit. AB - The authors present their clinical experience with the oral administration of lorazepam, methadone, and pentobarbital to prevent or treat withdrawal symptoms following prolonged sedation in the PICU patient. The 3 patients presented required prolonged sedation for mechanical ventilation. Different agents were used for sedation in the 3 patients including intravenous fentanyl, midazolam, and pentobarbital. The switch to oral agents must take into consideration the differences in potency, half-life, and oral bioavailability between the agents. The authors discuss the appropriate conversion factors for opioids, benzodiazepines, and barbiturates. The switch to oral administration eliminated the need for intravenous access in the 3 patients and allowed for earlier discharge home. All 3 patients were discharged home on an oral, taper schedule. Such an approach may lead to earlier home discharge thereby improving the patient's quality of life as well as saving health care dollars. PMID- 7995869 TI - Immunoglobulins and IgG subclasses in children following severe head injury. AB - OBJECTIVE: To study immunoglobulin production after severe blunt head trauma in children. DESIGN: Serum for IgG, IgM, IgA, IgE, and IgG subclasses were drawn from 10 children admitted with severe head injury (ISS 31.2, GCS 5.4) on day 1, 7, 14 and 21 after injury. RESULTS: 5 of the 10 patients developed infection between 7 and 14 days and 2 died of complications of pneumonia. On day 1, IgM levels averaged 95.6% of the mean of the age-specific normal controls. By day 7, IgM levels averaged 383% (p < 0.01). While all patients were within the age specific normal range (+/- 2 SD) on day 1, 7 of 10 patients were above the normal range by day 7. There was no difference in IgM levels between infected and non infected patients. Five patients were below the age-specific normal range for IgG on day 1, with 3 still low on day 7. By day 21, IgG levels averaged 141% of the mean of the age-specific normal controls. IgG subclasses followed a pattern similar to total IgG levels. Marked increases in IgE were seen in 3 patients. CONCLUSIONS: IgM levels increased dramatically in all patients within seven days of the injury. While 50% of these children had a deficit of IgG in the first week, total IgG and IgA levels increased after injury, but not as rapidly as IgM levels. Unlike pediatric burn patients, there is no persistent hypogammaglobulinemia following severe blunt trauma in children. PMID- 7995870 TI - Inhaled nitric oxide for a severe respiratory syncytial virus infection in an infant with bronchopulmonary dysplasia. AB - OBJECTIVE: To report the first case of ARDS in children treated with nitric oxide (NO) inhalation. METHODS: A 13-months infant presented with BPD and severe hypoxemia related to RSV infection and ARDS. Inhaled NO was delivered in the ventilatory circuit of a continuous flow ventilator (Babylog 8000, Drager) in a concentration of 20-80 ppm for 7 days. NO and NO2 were continuously monitored (Polyton Draeger). Respiratory mechanics were evaluated by using the method of passive inflation by the ventilator. RESULTS: NO inhalation improved oxygenation (tcSaO2) and reduced respiratory system resistance without affecting arterial pressure. NO2 level remained below 5 ppm, and methaemoglobin level below 1%. The child survived without neurologic sequela. CONCLUSIONS: Two mechanisms to explain oxygenation improvement can be suggested: selective improvement in perfusion of ventilated regions and bronchodilation. PMID- 7995873 TI - Use of the intraosseous route in resuscitation in a neonate. PMID- 7995871 TI - Bedside assessment of myocardial performance in the critically ill. AB - No measurement of myocardial performance currently available in the ICU can be regarded is ideal. Table 2 summarises the main features of the major monitoring techniques. As many of the indices of myocardial performance are interdependent, quantifying the contribution of each component to overall cardiac function is not possible currently, and the clinical utility of monitoring each individually is not therefore established. Bedside measurements of LV dimensions, volumes and ejection fraction, and the other indices of systolic and diastolic function can now be made, but the case for their routine use in influencing clinical practice remains unproven. Transoesophageal echocardiography has an important and established diagnostic role and has been used successfully for continuous monitoring during surgery, but practical considerations seriously limit its potential for routine use. Radionuclide techniques allow the measurement of many of the same parameters and have the potential for continuous use, but practical problems and the additional risk of radiation exposure may limit this application in the critical care environment. Doppler techniques are non-invasive, provide continuous data and are simple to operate, but the data provided has important limitations. Although the pulmonary artery catheter has been in use for over twenty years, questions regarding the information is provides concerning myocardial function remain and the extent to which it should influence therapeutic decisions is still controversial. However with the development of additional facilities, particularly the continuous measurement of cardiac output the pulmonary artery catheter seems likely to remain the mainstay of bedside monitoring of myocardial performance in the critically ill in the immediate future. PMID- 7995872 TI - Management of deep Candida infection in surgical and intensive care unit patients. British Society for Antimicrobial Chemotherapy Working Party. AB - Deep Candida infections are increasing in incidence, especially in non neutropenic, intensive care patients including neonates. The attributable mortality of candidaemia and candida peritonitis is 37-38% with a 57% overall mortality. The BSAC set up a working party to develop recommendations for management in the absence of controlled trials. These recommendations focus on the role of the microbiology laboratory, management strategies, the respective roles of amphotericin B, flucytosine and fluconazole and long-term maintenance therapy. The indications for initiation of therapy are given special consideration. PMID- 7995874 TI - Inspiratory pressure/maximal inspiratory pressure ratio: a predictive index of weaning outcome. PMID- 7995875 TI - Severe cutaneous side effects of peripheral infusions with carbicarb half strength. PMID- 7995876 TI - Lack of efficacy of inhaled nitric oxide in ARDS. PMID- 7995878 TI - Does flumazenil antagonize baclofen? PMID- 7995877 TI - Pneumoperitoneum and asthma. PMID- 7995879 TI - In an age of reform, celebrating an early reformer. PMID- 7995880 TI - Men in nursing. PMID- 7995881 TI - AIDS: the dilemma of prevention. PMID- 7995882 TI - The challenge of ethical leadership in nursing. PMID- 7995883 TI - Ethical conflict in long-term care: is legislation the answer? AB - The Omnibus Budget Reconciliation Act of 1987 radically redefined the relationship between nursing facilities and their residents. To explore the impact of this autonomy-enhancing but controversial legislation on nursing operations in skilled nursing facilities, two focus groups were convened. Nurse administrators identified ways in which the recently implemented legislation facilitates or inhibits resolution of the ethical conflicts they face. Participants concluded that legislation alone was insufficient to create needed reform in long-term care and recommended a multifaceted approach. A model is presented for creating a community of caring that identifies regulatory reform, professional empowerment, and organizational redesign as catalysts for a change. PMID- 7995884 TI - Academic misconduct among nursing students: a multivariate investigation. AB - The purpose of the study was to determine the degree to which several independent variables correlate with perceived instance of academic misconduct among nursing students. Maslow's Need-Goal Motivation Model served as the guiding framework for the study. It was postulated that nursing students' perceptions of their peers' maturity, academic commitment, and neutralizing attitude would be correlated with perceptions of their peers' involvement in various forms of academic misconduct. Results indicated a moderately high degree of correlation exists among the variables (Function I Rc2 = 0.325; p < .001). PMID- 7995885 TI - The Graduate Record Examination as an admission requirement for the graduate nursing program. AB - The use of the Graduate Record Examination (GRE) as an admission criterion for the master's degree program was evaluated using data from student records of the population that graduated or dropped out of the State University of New York at Buffalo program between 1983 and 1992. The GRE correlated with first-year and overall graduate grade point averages, but it was a weaker predictor of performance than was the undergraduate grade point average. These findings are discussed in light of the negative consequences of using the GRE related to the recruitment of minority students, women, and older students. PMID- 7995886 TI - The impact of personal and situational variables on career patterns among nurses from three types of educational programs. AB - Relationships between educational preparation and employment choices were investigated in a study of the career paths of nursing graduates from three types of educational programs: a community college diploma program, a generic baccalaureate program, and a postdiploma baccalaureate program. Selected personal and work-related correlates of career paths for the three groups also were explored. All available graduates for the years 1984 to 1990 from the three programs (n = 1,544) were sent a self-administered questionnaire. Data were collected concerning demographic variables, employment details, ongoing professional development, and level of satisfaction with nursing. Analysis of the data demonstrated clear variations in the career paths of the three groups of graduates, supporting the belief that the type of educational program does indeed have a steering effect on the subsequent career choices of these nurses. PMID- 7995887 TI - Faculty perceptions of teaching on television: one school's experience. AB - Videoteleconferencing (or teaching on television) represents a means of growing importance for distant learners to gain greater access to nursing education. Research has identified a number of key issues for nurse educators to consider related to videoteleconferencing: teaching/evaluation strategies, faculty workload, rewards and incentives, and support structures. The authors conducted an evaluation survey using a case study approach aimed at describing the perceptions of a convenience sample of faculty members (n = 17) regarding their recent television experiences. The survey, conducted by means of a mailed questionnaire, examined perceptions centering on sources of support, reception site logistics, rewards teaching strategies, and future directions. Key findings included: overall, respondents perceived television teaching positively; reception site, administrative support, and peer support were important to faculty; additional preparation time was required for television teaching; teaching on television required changes in style and pedagogical strategies; and student-teacher interactions were affected by the medium. Findings have implications for the implementation of videoteleconferencing operations, recruitment of faculty for television teaching, and evaluation of videoteleconferencing operations. PMID- 7995888 TI - The interactive seminar: an educational approach for voluntary HIV testing in a drug dependence treatment unit. AB - Acquired immune deficiency syndrome (AIDS) is a pandemic disease with no known cure and limited effective strategies for prevention and control. It is one of the most devastating illnesses in contemporary society, and since 1982, certain populations, including intravenous drug users (IVDU), have been targeted as being at high risk for AIDS. Education is one strategy that seeks to address AIDS and the needs of IVDU. This retrospective study focused on the use of the interactive seminar or small-group discussion as an educational method to identify and describe its effect on the rate of voluntary human immunodeficiency virus (HIV) testing among male subjects in a drug dependence treatment unit (DDTU). The subjects, 25 to 62 years old, were in treatment at a Medical Center for Veterans that was located in an urban environment. The medical records of 118 patients admitted to the unit during the year before and the year after the introduction of an HIV interactive seminar were studied. Analysis of data showed that drug users who participated in the interactive seminar had a higher rate of voluntary HIV testing than did those who did not participate; IVDU who participated in the interactive seminar had a higher rate of voluntary HIV testing than IVDU who did not participate in the seminar; drug users who completed the detoxification treatment and participated in the interactive seminar had a higher rate of voluntary HIV testing than did those who did not participate in the interactive seminar.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7995890 TI - Children's vision: where primary optometric care begins. PMID- 7995889 TI - The evolution of a profession: where do boards of nursing fit in? AB - Differentiation between the structure and functions of Boards of Nursing and the professional association is important to understanding the evolution of nursing as a profession. This descriptive exploratory study revealed that Boards of Nursing usually have 5 members who are appointed by and can be removed by the governor of the state. All Boards are responsible for education and licensing at the professional entry-level but may not be responsible beyond that level. In contrast to the professional association, Boards report appreciable variability in structure and administration. Boards differ from the professional association in source of power and focus on the protection of the public rather than improvement of practice. PMID- 7995891 TI - Pediatric drug therapy: are we providing the best care possible? PMID- 7995892 TI - Visual recognition memory in specific learning-disabled children. AB - BACKGROUND: Reading depends on the efficient storage and retrieval of visual and verbal information. Some studies have shown deficits of specific learning disabled children in the recall and recognition of visual stimuli. This deficit is usually interpreted to be secondary to a verbal labelling deficiency. In this experiment, we presented serial lists of complex geometric stimuli to a group of specific learning-disabled children (LD) and a non-disabled control group (NLD) at both the elementary and secondary school levels. We hypothesized that the NLD visual recognition performance would be superior to that of the LD group at the elementary school level, but not at the secondary school level. We further hypothesized that the difference was related to inefficient primary visual rehearsal strategies. METHODS: 20 elementary school children (11 LD and 9 NLD) and 31 secondary school children (15 LD and 16 NLD) were presented serial lists of four geometric figures. A probe was presented after a 1 second delay. The subjects pressed a key if the probe was in the list ("same" response) or another key if the probe was not in the list ("different" response). Type of response (correct or incorrect) and reaction time was measured at each serial position for "same" and "different" responses. RESULTS: At the elementary school level, there was a significant visual recognition memory advantage of the NLD group over the LD group (F(1,8) = 6.83, p = 0.018), but there was no significant difference between these groups at the secondary school level. There was no significant difference in the reaction time between the groups at either of the two levels. CONCLUSIONS: LD children have poorer visual recognition memory performance than NLD children for complex geometric patterns. Since there was no difference in reaction time between the two groups, attentional or encoding deficits can not adequately explain the recognition memory differences. The results can best be explained by inefficient visual rehearsal strategies with a small pool of visual items that are unfamiliar and difficult to code verbally. The serial recognition task can be used effectively by the optometrist to discriminate the performance of LD and NLD children. PMID- 7995893 TI - Comparison of Irlen scotopic sensitivity syndrome test results to academic and visual performance data. AB - Irlen has defined a condition called Scotopic Sensitivity Syndrome (SSS) that is associated with reading problems. According to Irlen, SSS can be treated by the use of colored filters, but there is disagreement about the existence of SSS and the efficacy of colored filter therapy. METHODS: Thirty-nine children participated in the study: 24 were academically normal, nine had specific reading problems, and six had problems in multiple academic areas. SSS levels and preferred overlay colors were determined. Optometric test data were also available for each subject. RESULTS: No significant relationships were found between academic classification and degree of SSS. There were also no significant relationships between preferred overlay color and any other variables. There was, however, a significant tendency for subjects with higher SSS levels to be candidates for vision therapy and to derive greater benefit from the colored overlays. CONCLUSIONS: Many questions about the use of colored filters for the treatment of reading problems remain unanswered. Among these are questions dealing with whether the M-pathway anomalies found in some dyslexics are also present to a lesser degree in other cases of reading disabilities, and how colored filters could re-balance the M- and P-pathways. Is it the color of the filter itself that is critical, or is it the change in luminance or contrast produced by the filter that seems to make it easier for some subjects to read? More research will be needed to answer these questions. PMID- 7995894 TI - Eye movement dysfunction vs. language delays in migrant children. AB - BACKGROUND: The Developmental Eye Movement Test (DEM) is a popular visual-verbal saccade test. An advantage of the DEM is that patients with below-average verbalization or automaticity can be distinguished from patients with eye movement coordination problems. The standardized norms for the DEM were previously determined in a sample of suburban and urban children with expected age to grade levels. We hypothesize that language difficulties common in some minority groups would be reflected by subnormal DEM automaticity but not eye movement dysfunction. METHODS: A group of children in the U.S. Department of Education's Massachusetts Migrant Summer Education Program were prospectively studied with the DEM. The sample included 84 subjects (age 7-12) from various ethnic and educational backgrounds. RESULTS: Significant difference was found for most age levels in automaticity in migrant children compared to the DEM norms (independent t tests p < 0.05 DEM vertical and horizontal). However, few differences in eye movement coordination was found (p > 0.05 DEM ratios and errors). CONCLUSIONS: The data supports the hypothesis that language barriers inherent in this population are reflected by lower automaticity, but not eye movement dysfunction, as measured by the DEM. The results are important for optometrists because they demonstrate the importance of taking language and cognitive development into account before diagnosing eye movement dysfunction in culturally different children. PMID- 7995895 TI - Optometric management of congenital cataracts. AB - BACKGROUND: Congenital cataracts have historically been a major cause of visual impairment in children. Their treatment improved once deprivation amblyopia became better understood. Many children born with congenital cataracts are now able to develop good functional levels of visual acuity. Early detection and surgical removal of the cataracts are only the first steps in the treatment. RESULTS: The optical correction of the resulting aphakia, usually with contact lenses, and the long term treatment of amblyopia when required are invariably more difficult. The pediatric optometrist is particularly well suited to manage this postsurgical treatment of patients with congenital cataracts. PMID- 7995896 TI - Detecting ocular and visual anomalies in a vision screening setting using the Lang stereotest. AB - BACKGROUND: Effectiveness of random dot stereotests (RDS) as vision-screening procedures vary. In this investigation, 183 school-aged children (6-10 years) had their vision screened using the Modified Clinical Technique (20.7 percent referred) and the Lang stereotest (12.0 percent referred)--a type of RDS test not requiring dissociating glasses. For the populations as a whole, the Lang test demonstrated low sensitivity, 31.6 percent; yet specificity was high, 93.1 percent. The phi coefficient (phi) was +0.31 for use as a sole procedure that rose to +0.43 when combined with Snellen acuity and +0.60 when combined with refractive error. Test/retest reliability conducted on a subgroup of 27 children showed a correlation (r) of +0.69. In another subgroup of 17 multiply handicapped children, 41.2 percent were referred by the Lang stereotest; the sensitivity was 100 percent, specificity 90.9 percent and effectivity (phi) +0.88. While not as effective as reports of the Random Dot E stereotest in screening 6-10 year old children, results obtained with the Lang stereotest in the group of exceptional children are remarkable. PMID- 7995897 TI - Effect of resisting tonometry on intraocular pressure. AB - BACKGROUND: Children and patients with developmental delay frequently resist the procedure of tonometry. Intraocular pressure (IOP) readings, if obtained under stressful circumstances, may have questionable reliability because IOP is influenced by numerous factors characteristic of the uncooperative patient. These factors include possible increases in arterial blood pressure, intraocular vascular engorgement, and pressure on the globe. A study of the effect upon IOP of these factors occurring simultaneously has not been reported previously. METHODS: We measured IOP using the Tono-Pen on 40 cooperative adults under normal conditions and again under conditions simulating the resistant patient. RESULTS: Paired t-test revealed a statistically significant difference between IOP readings under the two conditions (p < 0.001), with IOP under "resistant" conditions showing more variability and averaging 6mmHg higher than under normal conditions. CONCLUSIONS: We conclude that IOP readings in resistant patients should be viewed with caution. The possibility of obtaining false high readings in these patients could lead to unnecessary glaucoma evaluations if based only on elevated IOP readings. PMID- 7995898 TI - The SolCos model: facilitating reminiscence therapy. AB - 1. Reminiscing is an effective strategy for processing information, feelings, and thoughts into a broader life perspective. 2. The SolCos Reminiscence Model has been developed to facilitate reminiscence therapy. It may be used singularly or in a group, and with elders and persons who are terminally ill. 3. The model, which consists of processes, items and outcome categories, is a fluid construction and may be approached nonlinearly. The model is both beneficial and longitudinally cost-effective for the individual and yields a lasting benefit to the practitioner, both personally and professionally. PMID- 7995899 TI - The terminally ill: serenity nursing interventions for hospice clients. AB - 1. Serenity is an inner peace that is independent of external events. It often is desired by persons near death. 2. Information about nursing interventions to facilitate clients' serenity, however, is missing from the literature. 3. In the study presented, pain control, therapeutic touch, and assisting clients to build trust were the three highest-ranked interventions on both effectiveness and frequency of use. PMID- 7995900 TI - Use of siderails: rethinking a standard of practice. AB - 1. Policy and/or tradition is not adequate rationale for siderail use in light of current information indicating that siderails can be a hazard. 2. If a client is going to climb out over the siderail, the siderail increases risk for client injury. In such cases siderail use cannot be justified. 3. The nurses's goal is not to eliminate siderail use, but to individualize it--to use siderails only in cases in which they increase the safety, security, and mobility of clients. PMID- 7995901 TI - Skin care strategies in a skilled nursing home. AB - 1. Pressure ulcers continue to be a serious problem in nursing home settings. They are significant as a source of discomfort and disability among nursing home residents, as well as a source of financial concern for the institutional agencies responsible for resident care. 2. Prevention and intervention at the earliest stages of pressure ulcer development offer the most effective approaches to mediating the human and economic costs imposed by pressure ulcers. 3. Strategies that are effective in reducing both the development and severity of pressure ulcers can be successfully implemented in long-term care settings. Further studies are needed that will provide additional support for the strategies and protocols used in this study. PMID- 7995902 TI - Managing disruptive responses to bathing by elderly residents. Strategies for the cognitively impaired. AB - 1. Persons with altered cognition are more prone to display inappropriate behaviors because of decreased ability to accurately interpret environmental cues, and increased frustration in combination with reduced inhibition. 2. Disruptive and agitated behaviors are commonly associated with the provision of assistance with activities of daily living, particularly bathing and dressing. 3. A preventive approach intended to reduce the occurrence of distress and disruptive behaviors in cognitively impaired residents during showering and bathing respects long-standing routines and preferences of the patient. PMID- 7995903 TI - Long-term care: retention of nurses. AB - 1. A growing nursing shortage and a growing population of older individuals with complex needs have created an unprecedented demand for qualified nurses in long term care. 2. Nurse retention is associated with the status of salary benefits, paperwork, staffing, and supplies; the quality of relationships with residents, families, and peers; and the extent to which nurses feel autonomous and empowered with the authority to make nursing decisions regarding their patients. 3. Nurse researchers in both clinical and educational settings must place a high priority on developing methods of making long-term care a more attractive and satisfying practice setting. PMID- 7995904 TI - Influence of caregiving on families of older adults. AB - 1. The needs of caregivers often are overlooked when health professionals focus attention on the needs of the one requiring the more obvious care. Caregivers and potential caregivers need to understand the potential hazards to their physical, mental, and spiritual health. 2. Nurses, pastors, social workers, and physicians could benefit from increased knowledge about the influence of caregiving on the individual. 3. Further research is needed on interventions for caregivers. Research on the care recipient and the family, as well as on caregiving over time, would help promote health. Persons who have developed effective coping patterns for caregiving should be studied. PMID- 7995905 TI - [Plea for the formation of regional resuscitation for the newborn at birth]. PMID- 7995906 TI - [Methods of second trimester pregnancy termination and evacuation of in utero dead fetuses. Value of mifepristone]. AB - The authors present a review of the literature on the current methods of second trimester termination of pregnancy and labour induction for fetal death. Prostaglandins are efficient, but may cause side-effects (nausea, vomiting) and painful contractions. Natural PGs (PGF2 alpha and PGE2), induce fetal expulsion in about 80% of cases within 24 h. PG analogues (sulprostone and gemeprost), are, presently, more used, and lead to fetal expulsion in 90% of cases, with less side effects. Mifepristone, an antiprogesterone steroid, increases uterine activity, sensitizes myometrium to PG action, and induces cervical priming. Several clinical trials point out the advantage of mifepristone use, 24 to 48 h before PG. So, the duration of termination, and the PG dosage are reduced by half. A clinical protocol for second trimester termination, with mifepristone, and PG analogues, is proposed. In case of fetal death, labour induction is now accepted. The expulsion of a dead fetus is easier than a live one. PG and analogues show a good efficacy: > 90% success within 24 h. Mifepristone, alone, leads to fetal expulsion in 2/3 of cases, within 72 h, without side-effects. A clinical protocol of induction with mifepristone and PG in case of fetal death is proposed. In these two difficult clinical cases, mifepristone is of great interest, in reducing duration of termination, and increasing comfort and security for the patients. PMID- 7995907 TI - [Radiosurgical correlations of 61 breast microcalcification foci]. AB - OBJECTIVE. Diagnostic value of breast clustered microcalcifications discovered by mammography. DESIGN. A retrospective study. SETTING. Oncology Center of Rennes. SUBJECTS. 58 women (study group) with breast clustered microcalcifications without palpable tumour were operated. SURGERY. Prior to surgical removal of microcalcification, needle localization was performed. Histological results. We observed, 36 benign lesions (59%), 25 carcinomas (45%), 10 of them in situ and 15 infiltrative. RESULTS. Different radiological parameters were studied in relation to histological results, the vermicular morphology of microcalcification, an increased number, their triangular aspect, provide clue to the presence of breast carcinoma. The cluster of stippled calcification is not, in our series suggestive of a carcinoma, but also requires histopathological study, owig to the fact that in such cases, we have as many carcinomas as benign lesions. FINDING. Careful analysis of microcalcifications, within the clinical context, ensures a safe attitude, and enables one to operate only carcinomas. PMID- 7995908 TI - [Value of penis endoscopy in sexual partners of women with condylomatous or dysplastic lesions]. AB - TYPE OF STUDY: A retrospective study of 532 male sexual partners of patients who were examined for condylomatous or dysplasic lesions of the lower genital tract between January 1990 and June 1993. AIM: To evaluate the balanoscopy examination. The value of this examination for the follow-up of papilloma virus and dysplasic lesions in women. METHOD: Balanoscopy was performed after application of acetic acid (5%). Lesions were treated with viralytic agents or by CO2 laser destruction. Computer analysis of the data from the microscopic examination and treatment in partners was performed. MAIN RESULTS: Globally, peniscopy revealed a papilloma virus lesion in 43.3% of the cases. Nevertheless, for infectious lesions (condylomas) in women, 63% of the women had a papilloma virus lesions. CONCLUSION: Severe dysplasia of the penis is rare in our geographical area and balanoscopy is useful for the eradication of sexually transmitted diseases, sometimes for oncological examinations and to decrease the incidence of recurrent condylomatous or dysplasic lesions in women partners. Globally, the results are disappointing since the rate of recurrence was similar whether or not the male partner had been examined. The only difference was in case of rapid effective treatment in the partner which was obtained in 27% of the partners. PMID- 7995909 TI - [The "hazards" of using a Gore-Tex sling in the treatment of stress urinary incontinence]. AB - OBJECTIVE: To analyze the use of the Gore-Tex in the treatment of exertion incontinence. METHODS: During 1991, two gynecology units used the Mouchel technique and a Goebell-Stoeckel type technique in 72 patients with exertion incontinence, alone in 36 and in combination with a cure for prolapsus in 36 others. Results were analyzed with the chi 2 squared test and the Student's test for paired series. RESULTS: The rate of incontinence was 65% with a range from 60 to 66.7% according to the type of technique used and whether a cure for prolapsus was also performed. Gore-Tex was not well tolerated in 23/72 cases. Rejection was seen in 20 to 37.5% according to the type of vaginal suture and the type of protection. CONCLUSION: The high rate of rejection suggests prudence in using Gore-Tex. PMID- 7995910 TI - [Should laparoscopic lymphadenectomy modify the therapeutic protocols for cancer of the cervix?]. AB - A precise evaluation of lymph node involvement in cases of cancer of the cervix can be obtained by performing laparoscopic lymphadenectomy. This technique has a sensitivity and a specificity of almost 100%, and is currently the best way to diagnose nodal involvement, apart from laparotomy. However, the role of laparoscopic lymphadenectomy in therapeutic protocols has not been precisely defined. The possibility of knowing beforehand the status of the lymph nodes has led to the proposal of new protocols where treatment modalities would be adapted to the findings of an initial laparoscopic lymphadenectomy. Three protocols have been proposed: some authors counterindicate colpohysterectomy in N+ patients and reserve surgery for N-patients: however, this attitude does not take into account current knowledge of tumour radiosensitivity. In case of an exclusive radiotherapy, radiotherapy could be adapted according to laparoscopic findings, but the benefit of surgical exercsis would be lost and patients would then be exposed to late pelvic relapse. Finally, laparoscopic lymphadectomy could be used in the treatment of early stage cancers, in association with a vaginal colpohysterectomy. Morbidity and survival rates of studies currently being conducted are still needed to evaluate this last protocol. Until these results are known, associating radiotherapy and colpohysterectomy remains the reference technique in cases of cancer of the cervix. PMID- 7995911 TI - [First trimester abdominal pregnancy and laparoscopic surgical treatment. 2 case reports of evolving abdominal pregnancy treated with laparoscopy at 10 and 12 weeks]. AB - Abdominal pregnancy occurs rarely and few observations of laparoscopic surgical treatment have been published. We observed 2 cases at 10 and 12 weeks of amenorrhoea. During one of the operations, it was particularly difficult to establish haemostasis, demonstrating the problems involved with laparoscopic surgery, highly dependent on gestational age and trophoblastic localization. Based on the epidemiological and diagnostic data we propose a therapeutic protocol for laparoscopic surgery in first-trimester abdominal pregnancies, taking into consideration the cases previously reported and current care for extrauterine pregnancy and late abdominal pregnancy. PMID- 7995912 TI - [Total septate uterus with hemi-vagina and homolateral renal dysplasia]. AB - We report a rare case of uro-genital malformation in 18 years old girl. The malformation associate total septus uteri, hemivagina atretica dextra and homolateral dysplastic kidney. Dysmenorrhea, purulent discharges from cervix and vaginal tumor evocated the diagnosis, which was confirmed by ultrasonography, hysteroscopy and coelioscopy. Therapeutic attitude was total resection of vaginal septus and right nephrectomy. At today, seven cases were published in international literature. In all cases, renal aplasia was reported. Embryologic acknowlegements can't explain this malformation. PMID- 7995914 TI - [Prenatal diagnosis: perceptions of women concerning their pregnancies]. AB - After a pregnancy with a normal outcome what are women's perception and knowledge of prenatal tests performances? A survey was carried out during 1990, in the Bouches-du-Rhone area, on a representative sample of French speaking women who had just delivered a normal liveborn. The participation rate was 80% and the mean maternal age was 28.9. On average, 5 (4.7-5.1) prenatal ultrasound scans were carried out per pregnancy and 93% of the women thought that the main interest of this exam performed during the 4-5th month of pregnancy was to confirm that the foetus was normal; only 9% answered that when the scan was normal one could be sure that the fetus was normal. Among those responding, 87% were informed about the existence and the goal of amniocentesis: media were the first source of information about the test in 42%. The level of education was the major determinant of women's knowledge and this factor should be taken into account by the practitioner during the prenatal surveillance. PMID- 7995913 TI - [Evaluation of bone density of the calcaneum using ultrasound attenuation in menopausal women]. AB - The results of bone density of the calcaneum measured with ultrasound in 107 menopaused women were compared with reference values provided by the manufacturer of the Walker Sonics machine and with the results of quantitative densitometry obtained with computed tomography of the calcaneum and lumbar vertebrae. The coefficient of correlation was 0.57 for the calcaneum and 0.45 for the vertebrae and was confirmed by the kappa index which was 0.58 and 0.54 respectively, indicating that bone density measurement with ultrasound attenuation is a simple non-invasive non-radiating technique which is a promising method for exploring osteoporosis in menopaused women. PMID- 7995915 TI - [Recurrence of common truncus arteriosus. Prenatal diagnosis of a case report]. AB - We report a case of isolated truncus arteriosis diagnosed prenatally which recurred during a subsequent pregnancy. This observation would suggest an increased risk of recurrent single trunk malformation as compared with other congenital heart diseases, in agreement with our understanding of the genetic processes involved. A prenatal screening can be achieved with a systematic examination of the fetal morphology. Prognosis is severe and prenatal diagnosis is difficult. PMID- 7995916 TI - [RU 486 and sulprostone in pregnancy termination in the 2nd and 3rd trimesters]. AB - OBJECTIVE: Describe our experience with the RU 486 (mifepristone) in case of pregnancy termination induced by sulprostone. METHOD: Prospective non controlled study in the department of Fetal Medicine of the "Institut de Puericulture de Paris". 158 women undergoing termination of pregnancy during the second and third trimester received a single dose of 600 mg of RU 486, 36 hours prior to infusion of 100 micrograms/hour of sulprostone. MAIN OUTCOME MEASURES: Delay between sulprostone therapy and diagnosis of labour duration of delivery. Prostaglandin doses used and frequency of secondary effects. RESULTS: The mean time between sulprostone administration and diagnosis of labour (146.5 +/- 106 minutes) as well delay of delivery (592.2 +/- 504 minutes) corresponded to the results reported in the literature. The primigravid women needed higher doses of prostaglandin and consequently experienced more secondary effects. No severe secondary effects were observed in this study. CONCLUSION: RU 486 is a satisfactory treatment for pregnancy termination during the second or third trimester. PMID- 7995917 TI - [Insulin dependent diabetes and pregnancy: evaluation of the insulin pump]. AB - OBJECTIVE: To evaluate the effectiveness of continuous insulin infusion (insulin pump) on the materno-foetal morbidity during pregnancy in patients with insulin dependent diabetes mellitus. METHODS: A retrospective study from 1980 to 1991. SITE. Gynecology-Obstetrics Unit, University of Caen. POPULATION: Eighty-one patients with insulin-dependent diabetes mellitus known to be affected before their pregnancy were followed in the unit from 1980 to 1991. This population was divided into two groups: in the first group, an insulin pump was installed before 15 weeks of amenorrhoea (n = 36) and in the second group, conventional treatment was given with three daily injections of insulin or with a pump installed after 15 weeks of amenorrhoea (n = 45). RESULTS: In the first group with the insulin pump before 15 weeks, there was a higher proportion of severe diabetes, the first consultation occurred earlier, there were half as many cases of neonatal jaundice and the length of hospitalization during the first trimester of pregnancy was longer. There was no difference in Apgar scores, cord pH, birth weight and the proportion of foetal macrosomia, length of the hospitalization in the neonatality ward, rate of malformation, infection, low blood glucose and calcium, transitive respiratory distress and neonatal polycythaemia, length of hospitalization of the mother during the second and third week postpartum, the rate of urinary infection, high blood pressure, hydramnios during pregnancy, delivery route, haemoglobin Alc or fructosamine during pregnancy. There was no perinatal death. CONCLUSION: Although there was no significant difference in the results, which may be explained by the higher number of severe cases of diabetes in the first group, the use of the insulin pump did not appear to improve control of blood glucose levels, and thus to improve the materno-foetal prognosis, except by the bias of earlier attentive management of the pregnancy which led to better outcome. PMID- 7995918 TI - [Crohn's disease with isolated vulvar localization and pregnancy. A case report]. AB - Extra-intestinal manifestations of Crohn's disease are well described. A very uncommon gynaecologic manifestation of this disease is vulvar involvement. Till now, sixteen cases have been reported in the literature. We report a case of a pregnant woman with isolated vulvar involvement, without bowel manifestations. The diagnosis have been clinically uncertain, but the histopathology goes with Crohn's disease. Discussion point out the difficulties in diagnosis and management of this vulvar condition, and of its association with pregnancy. PMID- 7995920 TI - [Separate birth 30 days after a premature delivery in a twin pregnancy. A case report]. AB - The author reports an exceptional observation concerning a delayed delivery of a second twin born at 34 weeks' gestation. The first infant was born 30 days before. The "fetal retention" of the second twin seems to improve its vital prognostic, 12 months later, the infant was in full growth and showing a good health. PMID- 7995919 TI - [Torsion of the pregnant uterus]. AB - The authors report a case of 180 degrees torsion of the pregnant uterus. Torsion has been defined as a rotation of more than 45 degrees of the uterus around its long axis and is rare in humans. Clinical diagnosis is difficult since symptoms are either absent or non specific (cervical dystocia, painful uterine contractions, dynamic hypertonia...). Uterine torsion is often associated to pathologies of the uterus such as uterine myomas or congenital deformities, abnormal fetal presentations, pelvic tumours or abnormal pelvis. Maternal prognosis is good after surgical treatment, however, perinatal mortality remains high. PMID- 7995921 TI - [Maternal mortality in Guinea: magnitude and perspectives]. AB - In recent years maternal mortality in developing countries has become a public health priority for international organizations. However, measuring the true magnitude of this problem is the subject of much methodological debate. In less than a century, the rate of maternal mortality in most industrialized countries has decreased one hundred-fold. In contrast, the rate remains very high in most developing countries, particularly in Africa. In this article based on the studies conducted in Guinea we review various operational proposals which may contribute to improving maternal health and reducing maternal morbidity and mortality, with particular reference to the work of the French speaking organization "Sante Maternelle Internationale". PMID- 7995922 TI - [Primary prevention trial of breast cancer by tamoxifen: the position of the French Society of Mammography and Breast Pathology]. PMID- 7995923 TI - [Tubal sterilization. Survey of the National College of French Gynecologists and Obstetricians]. PMID- 7995924 TI - Mitochondrial DNA variation among the Drosophila athabasca semispecies and Drosophila affinis. AB - Morphology, allozymes, and levels of postreproductive isolation indicate that the semispecies of Drosophila athabasca are as recently diverged as typical populations within a Drosophila species. However, levels of behavioral isolation, divergence in male mating song, and divergence in X-chromosome inversions suggest a much more ancient divergence. In this article, we have examined mitochondrial DNA restriction site variation within and among the three semispecies. These data support the hypothesis that the three semispecies of Drosophila athabasca are at least as recently diverged as are typical populations within other species of Drosophila. Male mating song, behavioral isolation, and X-chromosome differences thus appear to have evolved very rapidly. In addition, hypothesized phylogenetic relationships of these three semispecies, based on our mtDNA data, are identical to those based on allozymes and chromosomal inversions. According to this phylogeny, recency of ancestry is not well correlated with levels of behavioral isolation, whereas patterns of sympatry and allopatry are. These patterns strongly implicate the action of selection in the rapid evolution of behavioral isolation and X-chromosome gene arrangement. PMID- 7995925 TI - Colonization of America by Drosophila subobscura: the founder event and a rapid expansion. AB - The recent colonization of the American continent by Drosophila subobscura offers a unique opportunity to analyze the response of different genomic entities to a new environment. Here, results from a study of 15 allozyme loci in six North American and seven South American populations are compared with existing data from Palearctic populations. In general, only alleles with a frequency higher than 0.1 in European populations are present in America. The observed alteration in allele frequencies can be explained by a founder event. Although some significant latitudinal clines for allozyme frequencies have been detected, the results obtained are not as clear-cut as are those for chromosomal inversions. Overall heterozygosity is similar between North and South American populations and does not differ from that of Palearctic populations. This observation experimentally corroborates the results provided by theoretical models in which the average heterozygosity per locus depends not only on the size of bottleneck but also on the rate of population growth. The resemblance between North and South American populations is clearly manifested by a geometrical representation using Bhattacharyya's distance and a multidimensional scaling technique. Furthermore, these American populations are clearly differentiated from the Palearctic populations. PMID- 7995927 TI - Gene mapping in the spider monkey (Ateles paniscus chamek). AB - Sixteen isozyme markers have been assigned to the chromosome complement of the neotropical primate species Ateles paniscus chamek using three somatic cell hybrid panels. Several genetic associations were found to be common between humans and this species, despite the fact that Ateles is a karyologically rearranged taxon. Conversely, several human gene clusters were disrupted, resulting in gene associations not previously found in other primates. A comparison with other primates and mammalian orders, for which gene maps are available, was carried out for a comprehensive evaluation of genome evolution in these disparate taxa. PMID- 7995928 TI - Carrier detection of ovine hemophilia A using an RFLP marker, and mapping of the factor VIII gene on the ovine X-chromosome. AB - Ovine hemophilia A is an X-linked recessive bleeding disorder. For diagnostic purposes, restriction fragment length polymorphism (RFLP) analysis in the region of the factor VIII (F-VIII) gene was carried out using human F-VIII gene probes. The probe St14, known to detect a highly polymorphic region that is closely linked to the F-VIII gene in humans, hybridized nonspecifically with DNA from sheep. Searching for intragenic RFLPs, the entire 9.0-kb coding sequence of the human F-VIII was used as a probe. Using the 1.8-kb SstI/KpnI F-VIII cDNA probe for hybridization, an MspI-RFLP with allelic bands of 5.8 kb (A1) and 4.2 kb (A2) was detected. A1 was in linkage phase with the mutated allele responsible for hemophilia A. The F-VIII locus in the sheep genome was assigned to the long arm of the X-chromosome in the region Xq24-q33, using in situ hybridization with a 3 kb human F-VIII cDNA probe to QFQ banded sheep metaphase chromosomes. PMID- 7995926 TI - Evolution of number and morphology of mammalian chromosomes. AB - Numerous hypotheses have been advanced to explain how selection might operate on the level of the chromosomal complement (chromosome selection) and how this process could be related to morphological divergence and speciation. Hypotheses emphasizing a general trend of increasing or decreasing diploid numbers in mammalian evolution are contradicted by documented studies from diverse families of mammals. However, certain selective forces were identified that could drive chromosomal evolution in certain lineages under limited conditions. Species with higher fundamental numbers and/or higher diploid numbers are expected to have increased genetic recombination. Increased recombination is advantageous in increasing variability and thus utilization of a wider niche, but decreased recombination allows fixation of new mutations (both genic and chromosomal) and thus increased potential for phyletic divergence and speciation. The species with higher diploid numbers are also less likely to undergo deleterious translocation and inversion events because of the position of the chromosomes in the nucleus. A decrease in diploid or fundamental numbers by fusions or inversions would be important as an initial event in phyletic divergence in some groups. A rearrangement in one chromosome also could affect nuclear structure or recombination in other chromosomes and, in some lineages, could drive the acquisition of additional rearrangements. It is suggested that changes in the level of recombination and in nuclear stability played a pivotal role in mammalian chromosome evolution. PMID- 7995929 TI - Genetic divergence in South African wildebeest: analysis of allozyme variability. AB - Genetic variability within the blue (Connochaetes taurinus) and black (C. gnou) wildebeests in South Africa was estimated from allozyme frequencies at 31 protein encoding loci. Seven loci, Ak-1, Alb, Est-D, Icdh-1, Mpi-1, Pgm-1, and Tf, were polymorphic in the blue wildebeest, but only two loci, Est-D and Tf, were variable in its congener. Average gene diversity was H = 0.018 +/- 0.013 in the black wildebeest and was significantly smaller than that, H = 0.081 +/- 0.030, in the blue wildebeest. The reduced level of heterozygosity in black wildebeest is most likely due to a bottleneck in population size in the early 1900s. The genetic distance between the two species was 0.059 +/- 0.027, which is consistent with an estimate of low mtDNA sequence divergence found previously. PMID- 7995930 TI - Minute fragment observed in a bovine pedigree with Robertsonian translocation. AB - A minute fragment was found in the metaphase plates obtained from one Holstein bull carrying Robertsonian translocation. The pedigree investigation indicated that three out of 34 offspring had the same minute fragment as their sire. Fluorescence in situ hybridization (FISH) studies with bovine satellite DNA revealed that the minute fragment was hybridized with this DNA and was part of the bovine centromere. We propose that the minute fragment is the product of centric fusion and is transmitted to offspring without being lost in the subsequent cell divisions. PMID- 7995931 TI - IL-7 drives donor T cell proliferation and can costimulate cytokine secretion after MHC-matched allogeneic bone marrow transplantation. AB - Transplantation of MHC-matched, allogeneic B10.D2 bone marrow plus T cells into BALB/c recipients ultimately results in chronic graft-vs-host disease (GVHD) and mortality 8 to 12 wk post-transplant. We have identified IL-7-specific mRNA in the spleens of BALB/c bone marrow transplantation (BMT) recipients during the first week post-transplant. The response by T cells from B10.D2-->BALB/c BMT recipients to stimulation with IL-7 in vitro during the early period after transplant was then examined. The findings indicated that within the first week post-transplant, spleen cells removed from recipients injected with allogeneic, but not syngeneic, T cells proliferated vigorously to rIL-7. Both IL-2-dependent and -independent components were identified. Depletion of responding cells before culture with anti-Thy-1.2 Ab virtually eliminated this response. We conclude that transplant of allogeneic T cells is required for the observed IL-7 response, and moreover, such cells proliferate after exposure to this cytokine in vitro. To determine whether IL-7 could have a functional effect on donor T cells, the production of IFN-gamma by T cells from allogeneic BMT recipients stimulated with anti-T cell receptor (i.e., anti-V beta) Ab was examined. IL-7 was demonstrated to enhance IFN-gamma production by donor T cells postallogeneic BMT. These results suggest that a cytokine presumably produced in the host for the physiologic function of hematologic reconstitution is playing an additional role during the early events after allogeneic BMT mediated via the expansion and augmented cytokine production by donor T cells. PMID- 7995933 TI - Delivery of nascent MHC class II-invariant chain complexes to lysosomal compartments and proteolysis of invariant chain by cysteine proteases precedes peptide binding in B-lymphoblastoid cells. AB - The intracellular trafficking, proteolysis, and dissociation of invariant chain (li) associated with nascent class II molecules was examined in B-lymphoblastoid cells. Metabolic labeling and Percoll gradient centrifugation was used to assess the kinetics of delivery and processing of class II-li complexes within the endocytic pathway. Catabolism of class II-li complexes rapidly followed their delivery from post-Golgi compartments to dense lysosome-like compartments distinct from early and late endosomes. Direct peptide binding assays revealed that class II molecules associated with even small N-terminal fragments of li failed to bind peptide. Cysteine protease inhibitors alone blocked li proteolysis/dissociation and accumulation of class II-li biosynthetic intermediates within lysosome-containing compartments. Active-site labeling of cysteine proteases in B cells was used to identify cysteine proteases capable of mediating li proteolysis within endosomal compartments. Our results indicate rapid, possibly direct, transport of nascent class II-li complexes from the Golgi/trans-Golgi network to dense lysosomal compartments wherein cysteine protease(s), likely including cathepsin B, mediate complete removal of li. Inhibition of cysteine protease activity results in the accumulation of incompletely processed class II-li complexes, which lack peptide binding ability, within lysosomal compartments. PMID- 7995932 TI - Characterization of fibroblasts with a unique defect in processing antigens with disulfide bonds. AB - A chinese hamster ovary (CHO) fibroblast, transfected with murine MHC class II genes, inefficiently stimulated CD4+ Th cells specific for OVA, hen egg lysozyme (HEL), and pork insulin which contain disulfide bonds. However, the fibroblasts elicited a T cell response to lambda repressor, which lacks disulfide bonds, and efficiently presented synthetic peptides. A somatic cell hybrid WALC, generated by fusing the hamster fibroblast with a murine L cell fibroblast, very efficiently processed OVA and HEL, suggesting that impaired processing was genetically complemented and was a recessive trait. The hamster fibroblasts were capable of processing two distinct denatured forms of OVA and carboxymethylated HEL, either as effectively or more efficiently than the B lymphoma cell. The CHO cells also displayed diminished disulfide reduction of an endocytosed [125I]tyramine linked to poly-(D-lysine) through a disulfide spacer compared with that of the cell hybrid, providing direct evidence for defective reductive cleavage by the CHO cells. Diminished aspartic acid-mediated proteolysis of Ag could not account for the phenotype, because cell lysates and separated organelles from the fibroblast possessed higher acidic aspartyl proteolytic activity than lysates and organelles from a B lymphoma cell. Thus, CHO cells exhibit a defect in processing Ag with disulfide bonds which is consistent with the impaired intracellular reduction of the disulfide bonds in endocytosed macromolecules. PMID- 7995934 TI - Human vascular smooth muscle cells poorly co-stimulate and actively inhibit allogeneic CD4+ T cell proliferation in vitro. AB - We compared immunologic functions of human vascular smooth muscle cells (VSMC) with those of endothelial cells (EC) cultured from saphenous vein. Both cell types can express comparable levels of MHC class II molecules. However, class II positive VSMCs, unlike ECs, do not stimulate resting CD4+ T cell proliferation. Limiting dilution analyses revealed IL-2-producing cells alloreactive to class II positive ECs but not VSMCs. Class II molecules on VSMCs are functional, inducing CD25 expression on resting CD4+ T cells and stimulating proliferation of CD4+ T cells that have been pre-activated by ECs. VSMC expression of the co-stimulator molecules CD44, CD54, CD58, and CD59 is comparable to EC expression, and neither VCAM-1 nor B7 are expressed on either cell. However, VSMCs are less efficient than ECs at co-stimulating IL-2 production by PHA-stimulated PBL. VSMCs but not ECs cultured across a Transwell inhibit CD4+ T cell proliferation to allogeneic ECs and, to a lesser extent, IL-2 production in the same assay. Inhibition of proliferation cannot be transferred by VSMC-conditioned media, nor reversed by inhibitors of prostaglandin synthesis, TGF-beta 1, or nitric oxide synthesis. CD4+ T cells cocultured with class II-positive VSMCs proliferate to a subsequent challenge with ECs from the same donor as well as freshly isolated T cells. We conclude that VSMCs express functional MHC class II molecules and stimulate pre activated T cells. However, VSMCs lack adequate costimulators to fully stimulate resting T cells, and VSMCs inhibit T cell proliferation. PMID- 7995935 TI - Prostaglandin E2 promotes B lymphocyte Ig isotype switching to IgE. AB - The mechanism by which PG of the E series (PGE) promote murine B lymphocyte IgE production was investigated. We previously reported that PGE, and other agents that increase intracellular cAMP, synergize with IL-4 and LPS to induce IgE and IgG1 production while inhibiting IgM and IgG3 synthesis. These data suggested that PGE may promote IL-4-induced class switching, but the mechanism by which PGE increases IgE synthesis remained obscure. We report here that 1) PGE increases (up to 14-fold) the number of splenic B cells secreting IgE, even though PGE mildly inhibits proliferation. 2) PGE acts on sorted surface IgM positive B cells, consistent with PGE acting on uncommitted B cells to promote class switching to IgE. 3) PGE synergizes with IL-4 to induce germline epsilon transcripts, demonstrating that PGE acts at the level of transcription in cells that have not yet switched to IgE. 4) In the presence of PGE, rearranged mature V(D)J epsilon mRNA transcripts can be detected earlier and at higher levels than with IL-4 and LPS alone. Taken together, these data provide strong evidence that PGE synergizes with IL-4 and LPS to direct isotype switching to the epsilon heavy chain gene in purified B lymphocytes. PGE is a potentially important in vivo immunoregulator, particularly with regard to IgE production and the genesis of allergy. In support of this hypothesis, there are numerous clinical conditions (hyper-IgE, trauma, sepsis, Hodgkin's lymphoma, arthritis) in which overproduction of PGE is coincident with elevated IgE titers. PMID- 7995936 TI - Heterogeneity of the circulating human CD4+ T cell population. Further evidence that the CD4+CD45RA-CD27- T cell subset contains specialized primed T cells. AB - CD27, a member of the TNFR family, is expressed on most but not all peripheral blood CD4+ T cells. The small fraction of CD4+ T cells with a CD27- phenotype exclusively reside within the CD45RA-CD45RO+ subset. We previously provided evidence that CD27- cells are functionally differentiated cells that have lost CD27 expression as a result of persistent antigenic stimulation. We here show that compared with CD4+CD45RA-CD27+ cells, CD4+CD45RA-CD27- lymphocytes have a high expression of the beta 1 integrins VLA-4 and -5 and of the beta 2 integrin CD11b. Molecules implicated in homing of T cells to peripheral lymphnodes like CD31 and CD62L (L-selectin) are poorly expressed on CD27- cells, whereas receptors involved in organ-specific homing, e.g., cutaneous lymphocyte Ag and HML-1 (alpha E beta 7), are present on CD27- rather than CD27+ T lymphocytes. CD27+ and CD27- cells do not differ notably in the expression of activation molecules such as CD25, CD38, and CD70 (CD27 ligand) but CD7 is markedly absent on approximately half of the CD27- cells. Analysis of mutations in the HPRT gene, as measurement for the amount of cell divisions that have occurred in particular T cell populations in vivo, showed that CD45R0+ cells have a 2 to 5 times higher mutant frequency than CD45RA+ cells, whereas CD45R0+CD27- cells do not differ in this respect from CD45R0+CD27+ cells. In line with this latter finding, cells in G2M phase can only be found in the transitional, CD45RAbrightCD45R0bright subset but not in CD45R0+, CD45RA-, or CD27- cells. Our results imply that the CD27- population contains tissue-specific, specialized "primed" T cells that evolve in vivo independently from extensive cellular division. PMID- 7995937 TI - Analysis of antigen receptor signaling in B cells from mice with a retrovirus induced acquired immunodeficiency syndrome. AB - MAIDS is a retrovirus-induced immunodeficiency syndrome in mice that has similarities to human AIDS. Because the functional defects in B cells from retroviral immunodeficiency syndromes have not been characterized in detail, we examined early and late parameters of B cell responses to IgM cross-linking in B cells from MAIDS and normal mice. Splenic B cells from mice with MAIDS have defective in vitro proliferative responses to LPS and anti-IgM-mediated stimuli, as well as to PMA plus calcium ionophore, indicating a generalized defect in proliferative response potential independent of specific receptor-mediated signaling. When early signaling parameters were analyzed in response to IgM cross linking, it was found that calcium flux in B cells from MAIDS mice was significantly reduced; this reduction was not accounted for by quantitative differences in cell-surface IgM expression and therefore indicates a defect in early signal transduction through the IgM receptor. The tyrosine phosphorylation response to IgM cross-linking was also markedly deficient; tyrosine phosphorylation of Ig-alpha, Ig-beta, and an undefined protein of 80 kDa was detected in MAIDS B cells after anti-IgM stimulation, at levels substantially less than those observed in normal B cells. Multiple other tyrosine phosphorylation events observed in normal B cells, including phosphorylation of GTPase-activating protein, P13-kinase, and syk kinase, were not detected in MAIDS B cells in response to IgM cross-linking. The defect in tyrosine phosphorylation seemed to correlate with reduced surface IgM levels on a subpopulation of MAIDS B cells. B cells from mice expressing the MAIDS retrovirus-induced immunodeficiency thus reflect defects in early signaling through the Ag-specific IgM receptor as well as a generalized defect in proliferative responsiveness. PMID- 7995938 TI - Multiple defects in innate and adaptive immunologic function in NOD/LtSz-scid mice. AB - The scid mutation was backcrossed ten generations onto the NOD/Lt strain background, resulting in an immunodeficient stock (NOD/LtSz-scid/scid) with multiple defects in adaptive as well as nonadaptive immunologic function. NOD/LtSz-scid/scid mice lack functional lymphoid cells and show little or no serum Ig with age. Although NOD/(Lt-)+/+ mice develop T cell-mediated autoimmune, insulin-dependent diabetes mellitus, NOD/LtSz-scid/scid mice are both insulitis- and diabetes-free throughout life. However, because of a high incidence of thymic lymphomas, the mean lifespan of this congenic stock is only 8.5 mo under specific pathogen-free conditions. After i.v. injection of human CEM T-lymphoblastoid cells, splenic engraftment of these cells was fourfold greater in NOD/LtSz scid/scid mice than in C.B17/Sz-scid/scid mice. Although C.B-17Sz-scid/scid mice exhibit robust NK cell activity, this activity is markedly reduced in both NOD/(Lt-)+/+ and NOD/LtSz-scid/scid mice. Presence of a functionally less mature macrophage population in NOD/LtSz-scid/scid vs C.B-17Sz-scid/scid mice is indicated by persistence in the former of the NOD/Lt strain-specific defect in LPS-stimulated IL-1 secretion by marrow-derived macrophages. Although C.B-17Sz scid/scid and C57BL/6Sz-scid/scid mice have elevated serum hemolytic complement activity compared with their respective +/+ controls, both NOD/(LtSz-)+/+ and NOD/LtSz-scid/scid mice lack this activity. Age-dependent increases in serum Ig levels (> 1 micrograms/ml) were observed in only 2 of 30 NOD/LtSz-scid/scid mice vs 21 of 29 C.B-17/Sz-scid/scid animals. The multiple defects in innate and adaptive immunity unique to the NOD/LtSz-scid/scid mouse provide an excellent in vivo environment for reconstitution with human hematopoietic cells. PMID- 7995939 TI - Cell cycle control of apoptosis in human leukemic T cells. AB - Eukaryotic cell cycle is regulated by feedback controls that can arrest the progress of the cell cycle at specific checkpoints. Failure of feedback controls may predispose cells to undergo apoptotic death in response to a variety of stimuli. Transformed cell lines often carry defects in one or more proteins that regulate cell cycle, and therefore can be used as a model to study how cell cycle controls cell death. The present study investigated whether TCR/CD3-induced apoptosis of human leukemic T cells is cell cycle dependent. Studies of Jurkat and Sup-T13, two human leukemic T cell lines, demonstrated that anti-CD3 Ab driven activation results in a transient, reversible inhibition of DNA synthesis in Jurkat cells, but results in a persistent, irreversible inhibition of DNA synthesis in Sup-T13 cells. Anti-CD3 mAb blocked Jurkat cells at the G1/S interface without inducing cell death. In contrast, anti-CD3 mAb allowed Sup-T13 cells to enter S phase but inhibited progression into G2 phase and triggered cell death. Electron microscopy showed that anti-CD3 mAb-stimulated Sup-T13 cells acquired the characteristic morphology of apoptosis. The nuclear DNA appeared as oligonucleosome-sized fragments by gel electrophoresis, and as an apoptotic peak displaying lower fluorescence than the DNA content of cells in G1 phase by DNA flow microfluorometry. DNA fragmentation correlated with entry into S phase. The DNA synthesis inhibitor aphidicolin arrested Sup-T13 cells at the G1/S interface and prevented the apoptosis. Therefore, DNA synthesis is required for executing the apoptosis program initiated by TCR/CD3 stimulation of Sup-T13 cells. These data are consistent with the hypothesis that the suicide of activated cycling T cells upon encountering autoantigens may be one of the mechanisms for the immune system to prevent autoimmunity. PMID- 7995940 TI - Rearrangement of a VH-associated LINE-1 element with the expressed IgH cluster in a murine myeloma cell line. AB - The MPC11 mouse myeloma cell line (IgG2b kappa) has yielded numerous variants in Ig heavy-chain production. One such variant, E5.7A14, fails to produce gamma 2b heavy chain but still produces kappa light chain. Comparison of the restriction maps of E5.7A14 and MPC11 has shown that in E5.7A14, the expressed MPC11VH gene has been deleted and replaced by a different DNA segment. Cloning and sequencing of the rearranged heavy-chain gene has identified the new DNA segment as a virtually full-length LINE-1 element that, in germ line, apparently lies in a inverted transcriptional orientation downstream of a previously unknown member (pseudogene) of the VH3609 gene family. The LINE-1 rearrangement was associated with an inversion of a 2-kb segment of the J-C gamma 2b intron and a deletion of switch sequences. The nature of the rearrangements and the sequences at recombination and inversion breakpoints suggest that the rearrangement event was mediated via class switch mechanisms. This is one of a limited number of reports that both characterizes a LINE rearrangement and localizes the germ-line origin of the particular LINE element involved. PMID- 7995941 TI - Characterization and expression of alternatively spliced IgE heavy chain transcripts produced by peripheral blood lymphocytes. AB - We have investigated the IgE heavy chain isoforms produced in vivo by analyzing the epsilon mRNA species present in unstimulated PBL and expressing them individually in a myeloma cell line. Seven epsilon mRNA species were identified by using reverse transcription-PCR, cloning, and sequencing analysis. These species included the classical secreted (epsilon CH4-S) and membrane-bound (epsilon CH4-M1'-M2) IgE and five alternatively spliced epsilon transcripts. At the protein level, the five alternatively spliced epsilon transcripts (epsilon CH4*, epsilon CH4-M2', epsilon CH4'-1, epsilon CH4'-1-M2, and epsilon CH3-13-CH4) corresponded to four epsilon heavy chain isoforms, in which various parts of the CH4 domain were replaced by new stretches of amino acids at the carboxyl termini. The same epsilon mRNA species also were present in the IgE producing myeloma cell line U266. However, except for the classical membrane and secreted IgE, the corresponding proteins could not be identified. To further characterize the epsilon CH4-S, epsilon CH4*, epsilon CH4-M2', epsilon CH4'-1, and epsilon CH4-M1' M2 species, we expressed them as chimeric mouse/human anti-4-hydroxy-5-iodo-3 nitrophenacetyl Abs in a mouse myeloma cell line. Only the classical secreted and membrane isoforms were found to be secreted or expressed on the cell surface, respectively, and the other forms were retained within the cells and degraded. These data suggest that some of the epsilon mRNA isoforms produced by PBL are aberrantly spliced mRNAs, the protein products of which are eliminated by post translational events. PMID- 7995942 TI - A simple mathematical model for the functional peptide/MHC/TCR interactions. AB - T cell-specific activation requires ligation of TCRs with peptide-MHC complexes on the APC. On the basis of simple chemical and statistical laws, we have constructed a mathematical model to describe this trimolecular interaction between effector and target cells, and we demonstrate its predictive value in the case of in vitro peptide Ag titration. Moreover, this model can generate mechanistic explanations for cellular immunity phenomena like anergy, peripheral tolerance, cell-mediated suppression, TCR antagonism, and thymic selection events. PMID- 7995944 TI - Characterization of the mouse lymphotoxin-beta gene. AB - Lymphotoxin-beta (LT-beta) is a member of the TNF family of ligands which when expressed with lymphotoxin-alpha (LT-alpha, i.e., the original LT or TNF-beta) forms a heteromeric complex with LT-alpha on the cell surface. The mouse gene structure was determined by both cDNA cloning and analysis of a genomic DNA fragment encompassing the TNF/LT locus in the H-2 region of chromosome 17. The mouse and human genomic structures were found to be similar in terms of location in the class III region of the MHC; however, the mouse gene lacks one intron found in most members of the family. Both the cDNA and the genomic sequences revealed an altered splice donor in the conventional intron 2 position, rendering it nonfunctional. The altered gene retains an open reading frame such that an additional 66 amino acids are inserted into the stalk region connecting the transmembrane domain with the receptor binding domain encoded by exon 4 in this type II membrane protein. Northern analysis showed that this gene is expressed predominantly in lymphoid organs. The outlining of the complete mouse TNF locus will further studies of the relationship between these genes and immune function. PMID- 7995945 TI - Characterization of regions of herpes simplex virus type 1 glycoprotein E involved in binding the Fc domain of monomeric IgG and in forming a complex with glycoprotein I. AB - Glycoprotein E (gE) and glycoprotein I (gI) of herpes simplex virus type 1 form a molecular complex that binds the Fc domain of monomeric IgG. Two approaches were used to define regions of gE-1 involved in monomeric IgG binding and complex formation with gI-1. First, we constructed 22 in-frame gE-1 linker-insertion mutants and, in cotransfection experiments with gI-1, assayed each mutant for IgG monomer binding and the ability to complex with gI-1. Nine mutants with insertions between gE-1 amino acids 235 and 380 failed to bind IgG monomers, whereas mutants outside this region retained binding activity. Each mutant reacted with several gE-1 mAbs, was detected at the cell surface, and was fully processed. Only two gE-1 mutants with insertions at residues 235 and 264 lost the ability to co-immunoprecipitate with gI-1, which defines a region of gE-1 that complexes with gI-1. As an additional approach, we assayed 8 gE-1/gD-1 fusion proteins containing large overlapping gE-1 peptides inserted within the ectodomain of gD-1 for binding of IgG monomers and complex formation with gI-1. Three fusion proteins containing gE-1 peptides that overlap at residues 183-402 bound monomeric IgG. This region of gE-1 includes the Fc binding region defined by linker insertion mutagenesis. Five fusion proteins containing gE-1 peptides that overlap at residues 183-288 were co-immunoprecipitated with gI-1, confirming results of gE-1 linker insertion mutagenesis. These studies define two regions on gE-1 involved in Fc binding activity, one that interacts with gI-1, and another that binds IgG. PMID- 7995943 TI - A human anti-insulin IgG autoantibody apparently arises through clonal selection from an insulin-specific "germ-line" natural antibody template. Analysis by V gene segment reassortment and site-directed mutagenesis. AB - We analyzed the structural correlates underlying the insulin-dependent selection of the specific anti-insulin IgG1 kappa mAb13-producing cell clone, derived from a patient with insulin-dependent diabetes mellitus treated with recombinant human insulin. First, we cloned the germ-line genes that putatively gave rise to the expressed VH and V kappa segments and used them to generate the full (unmutated) "germ-line revertant" of the "wild-type" (somatically mutated) mAb13, using recombinant PCR methods and an in vitro human C gamma 1 and C kappa expression system. The full "germ-line revertant" bound insulin specifically and in a dose saturable fashion, but with a relative avidity (AVrel) more than three-fold lower than that of its wild-type counterpart (Avrel, 1.69 x 10(-8) vs 4.91 x 10(-9) g/microliters). Second, we established, by reassorting wild-type and germ-line revertant forms of the mAb13 VH and V kappa segments, that the increased Avrel for insulin of mAb13 when compared with its full "germ-line revertant" counterpart was entirely dependent on the mutations in the VH not those in the V kappa chain. Third, we determined, by site-directed mutagenesis experiments, that of the three mutations in the mAb13 VH segment (Ser-->Gly, Ser-->Thr, and Ser- >Arg at positions 31, 56, and 58, respectively), only Arg58 was crucial in increasing the mAb13 Avrel (from 1.44 x 10(-8) to 5.14 x 10(-9) g/microliters) and affinity (Kd, from 189 to 59 nM) for insulin. The affinity enhancement mediated by the VH segment Arg58 residue reflected about a threefold decrease in dissociation rate constant (Koff, from 4.92 x 10(-3) to 1.54 x 10(-3) s-1) but not an increase in association rate constant (Kon, from 2.60 x 10(4) to 2.61 x 10(4) M-1 s-1), and it contrasted with the complete loss of insulin binding resulting from the substitution of the VH segment Asn52 by Lys. The present findings suggest that human insulin, a self Ag, has the potential to recruit a natural autoantibody-producing cell precursor expressing a specific surface receptor for Ag in unmutated configuration, and drive it through affinity maturation. They also show that binding of insulin by such a receptor can be enhanced or completely abrogated by a single amino acid change. PMID- 7995946 TI - Alteration of pulmonary macrophage function by respiratory syncytial virus infection in vitro. AB - Alveolar macrophages (AL) are the first line of defense against inhaled pathogens and are exposed to virus during the course of a respiratory syncytial virus (RSV) infection. Interference of virus with alveolar macrophage functions may contribute to the risk of acquiring secondary bacterial infections during or after respiratory tract infections with RSV or other viral agents. We studied whether murine AL get infected with RSV and whether they support viral replication in vitro. In addition, the effects of RSV on microbicidal and on immunoregulatory functions were examined. Only a subpopulation of AL expressed viral F proteins after exposure of these cells to RSV. Infected AL released only small amounts of infectious virus into the supernatant. The extent of virus replication in AL seemed to be dependent in part on the amount of IFN induced by the virus, as has been demonstrated by infection of lung tissue macrophages and AL in vitro. In general, RSV infection of pulmonary macrophages appeared to be abortive. Nevertheless, release of reactive oxygen intermediates, phagocytosis, and killing of protozoa were reduced in RSV-infected AL in comparison to noninfected AL. In contrast, RSV stimulated secretion of TNF-alpha, IL-1, and IL 6 in an infectious-dose dependent manner. Along with the increased cytokine release, accessory functions of AL were increased after RSV exposure. Thus, exposure of AL to RSV appeared to stimulate their immunoregulatory functions, whereas the microbicidal activity of these cells seemed to be severely diminished. PMID- 7995947 TI - Antitumor activities of subsets of human IL-2-activated natural killer cells in solid tissues. AB - Human NK cells can be separated into two functionally distinct subpopulations based on the ability to rapidly respond to IL-2 by adherence to solid surfaces. To determine functions of the NK cell subsets in solid tumor tissues, adherent (A) and nonadherent (NA) NK cells were evaluated for their ability to infiltrate multicellular tumor spheroids in vitro, to kill carcinoma (CA) cell targets in these spheroids, and to mediate antitumor activity in vivo. A-NK cells were less cytolytic than NA-NK cells against CA targets in single cell suspensions or in monolayers. However, A-NK cells showed a significantly better ability than NA-NK cells to infiltrate tumor tissues and kill tumor cells in spheroids of human squamous cell CA of the head and neck or breast CA. Perilesional delivery of human A-NK cells and IL-2 resulted in regression of established human squamous cell carcinoma of the head and neck tumors growing subcutaneously in immunosuppressed nude mice. Similarly, in a xenograft model of human gastric CA metastatic to liver of nude mice, a single intrasplenic injection of A-NK cells in combination with i.p. infusions of IL-2 significantly reduced the number of established hepatic metastases (p < 0.007) and prolonged survival of the mice (p < 0.003). In contrast, NA-NK cells were ineffective in either of the in vivo xenograft tumor models. These findings demonstrate that A-NK cells represent a biologically unique and important subset of NK cells that, in contrast to the rest of NK cells, function as effector cells in solid tumor tissues and, consequently, have a great antitumor therapeutic potential. PMID- 7995948 TI - Enhanced cytotoxicity of IFN-gamma-producing CD4+ cytotoxic T lymphocytes specific for T. gondii-infected human melanoma cells. AB - CD4+ lines specific for Toxoplasma gondii-infected human melanoma P36 cells were established from PBL of a patient with chronic toxoplasmosis. CD4+ CTL lines were obtained by weekly in vitro stimulation with T. gondii-infected P36 cells that shared HLA-DR4 molecules with the patient. The lytic activity of CD4+ CTL lines against T. gondii-infected P36 or T. gondii-infected autologous EBV-transformed B lymphoma (EBV-Ya) was inhibited by anti-HLA-DR mAb, whereas anti-HLA-A, B, C mAb failed to block the lytic activity. Thus, the cytotoxicity of CD4+ CTL lines against T. gondii-infected P36 was restricted by HLA-DR molecules. In response to Ag-specific stimulation, CD4+ CTL lines produced significant levels of IFN-gamma. Exogenously added IFN-gamma up-regulated the surface expression of MHC class II, but not of class I in T. gondii-infected P36 cells. In addition, the CTL activity against T. gondii-infected P36 cells was augmented when target cells were co cultured with IFN-gamma. These data indicate that CD4+ CTL-mediated cytotoxicity against T. gondii-infected melanocytes is enhanced by the autocrine production of IFN-gamma. Further, CD4+ CTL may play a role in the manifestation of toxoplasmic retinochoroiditis by killing T. gondii-infected melanocytes. PMID- 7995949 TI - Ligation of platelet/endothelial cell adhesion molecule 1 (PECAM-1/CD31) on monocytes and neutrophils increases binding capacity of leukocyte CR3 (CD11b/CD18). AB - Platelet/endothelial cell adhesion molecule 1 (PECAM-1/CD31) is a member of the Ig gene superfamily expressed on the surfaces of monocytes (Mo), neutrophils (PMN), and some T cell subsets, as well as on platelets and the intercellular junctions of endothelial cells. We used mAbs (mAb) against PECAM on Mo and PMN to mimic interaction with natural ligand. Such treatment resulted in the rapid increase of leukocyte beta 2 integrin-mediated adhesive function, as measured in two in vitro assays. Anti-PECAM-treated Mo bound more rapidly and in a CD18 dependent manner to cultured endothelial cells. Monovalent Fab fragments augmented binding significantly and intact IgG, bivalent F(ab')2 fragments, and secondarily cross-linked Fab fragments were even more effective. In a direct assay of CD11b/CD18 (CR3) function, PMN settling on surfaces coated with anti PECAM mAb (including Fab fragments) were stimulated to bind C3bi-coated erythrocytes. These studies demonstrate that, in addition to the previously described functions of PECAM-1, this molecule is capable of participating in an adhesion cascade resulting in the activation of Mo and PMN beta 2 integrins. This activation may be important for the CR3-dependent adhesion events that are critical in the emigration of Mo and PMN at sites of inflammation. PMID- 7995950 TI - Inhibition of chemotactic peptide-induced neutrophil adhesion to vascular endothelium by cAMP modulators. AB - An early event associated with neutrophil-dependent tissue damage involves the adhesion of neutrophils to the vascular endothelium and the subsequent release of oxygen-derived free radicals and granule constituents. Elevations in intracellular cAMP are known to inhibit free radical release but not lysosomal enzyme release. The role of cAMP in FMLP-induced neutrophil adhesion was examined in this study by using an in vitro model of neutrophil-endothelial cell adhesion. FMLP stimulated a time- and concentration-dependent increase in human neutrophil adhesion to HUVEC. FMLP-mediated adhesion was inhibited by a diverse group of cAMP modulators: forskolin, isoproterenol, phosphodiesterase IV inhibitors (rolipram and Ro 20-1724), but not phosphodiesterase III inhibitors (milrinone and bemoradan). Endogenous adenosine has previously been shown to mediate FMLP induced increases in cAMP enhanced in the presence of Ro 20-1724. In this study, adenosine deaminase prevented the inhibitory effects observed with rolipram and Ro 20-1724, implicating endogenous adenosine as a co-modulator of inhibition. FMLP stimulated neutrophil shape change and the surface expression of the beta 2 integrins CD11b/CD18 and CD11a/CD18. Both these responses were inhibited by rolipram but not bemoradan. With the use of 4,4'-diisothiocyanostilbene 2,2'disulfonic acid, we showed that mobilization of the intracellular pool of CD11b/CD18 paralleled adhesion. We conclude that neutrophil-endothelial cell adhesion is attenuated by elevating neutrophil intracellular cAMP and that inhibition of neutrophil CD11b/CD18 surface expression by cAMP accounts for this observed inhibition of adhesion. PMID- 7995951 TI - IgG immune complexes inhibit IFN-gamma-induced transcription of the Fc gamma RI gene in human monocytes by preventing the tyrosine phosphorylation of the p91 (Stat1) transcription factor. AB - Immune complexes (IC) modulate Ag-driven immune responses in part by their ability to inhibit IFN-gamma-dependent MHC class II expression. Because many genes, including MHC class II Ags, transcriptionally activated by IFN-gamma require the tyrosine phosphorylation of the transcription factor p91 (Stat1), we examined whether IC could suppress IFN-gamma-induced expression of the Fc gamma receptor I gene (Fc gamma RI) in human monocytes and whether this occurred through inhibition of p91 phosphorylation. Preincubation of monocytes on gamma globulin-coated dishes resulted in a 80% reduction in steady state levels of RNA for the Fc gamma RI gene. Nuclear run-on analysis confirmed that the inhibition was at the level of transcription. Treatment with IC resulted in no change in the IFN-gamma receptor number. In monocytes pretreated with IC, there was a 79% reduction in the formation of FcRF gamma, a p91-containing DNA binding protein complex that is rapidly activated by IFN-gamma, and which recognizes the gamma response region enhancer within the promoter of the Fc gamma RI gene. Furthermore, there was a marked reduction in the tyrosine phosphorylation of p91. Pretreatment with IC resulted in the inhibition of the tyrosine phosphorylation of the tyrosine kinases, Jak1 and Jak2, both of which are involved in IFN-gamma signal transduction. Therefore, culture of monocytes on IC inhibits IFN-gamma induced expression of the Fc gamma RI gene by preventing tyrosine phosphorylation of p91, probably by the associated inhibition of the tyrosine kinases Jak1 and Jak2. PMID- 7995952 TI - Characterization of surface lymphotoxin forms. Use of specific monoclonal antibodies and soluble receptors. AB - Lymphotoxin (LT) is a cytokine related to TNF, found in human systems in both secreted and membrane bound forms. The well characterized secreted form is a trimer of a single protein, LT-alpha, whereas the surface form is composed of a complex between two related molecules, LT-alpha and LT-beta. Because there is a distinct receptor for the complex, the membrane form is believed to signal via events different from those elicited by TNF and secreted LT-alpha. By using a battery of anti-LT-alpha and LT-beta mAbs, it is clear that two LT surface forms exist on the surface of PMA-activated II-23 cells, a human T cell hybridoma. Assuming that these surface forms are trimers, a minor form appears early after induction having an apparent stoichiometry of LT-alpha 2/beta 1 and is recognized by one group of anti-LT-alpha mAbs and the p55-TNF receptor. The second and predominant form has an apparent LT-alpha 1/beta 2 composition and is recognized by a second group of pantrophic anti-LT-alpha mAbs and the LT-beta receptor. Neither of the heteromeric forms nor a putative LT-beta homotrimeric form were found to be secreted. The properties of surface LT on the II-23 cell system were similar to those of the surface LT forms on Chinese hamster ovary cells transfected with both LT-alpha and LT-beta genes and a number of lymphoid tumor lines. These experiments point toward the LT-alpha 1/beta 2 complex as the predominant membrane form of LT on the lymphocyte surface, and this complex is the primary ligand for the LT-beta receptor. PMID- 7995954 TI - Potential requirement of a functional double-stranded RNA-dependent protein kinase (PKR) for the tumoricidal activation of macrophages by lipopolysaccharide or IFN-alpha beta, but not IFN-gamma. AB - We analyzed the expression of the dsRNA-dependent protein kinase (PKR) during the activation of murine macrophages to the tumoricidal state by LPS and/or IFNs. LPS induced PKR expression in a dose-dependent manner at levels that were comparable with those observed in response to IFNs. By using the PKR inhibitor 2-aminopurine (2-AP), we have shown that the pathways of macrophage tumoricidal activation elicited by LPS and IFN-alpha beta, but not by IFN-gamma, included a 2-AP sensitive step. In fact, LPS- and IFN-alpha beta-induced activation was inhibited by 2-AP, whereas the activation by IFN-gamma was not affected by the presence of the inhibitor. 2-AP did not affect the activation of protein kinase C or protein kinase A in intact cells. In the presence of 2-AP the up-regulation of IFN-beta mRNA by LPS was specifically inhibited, whereas the expression of glyceraldehyde 3-phosphate dehydrogenase mRNA or the induction of PKR remained unchanged, thereby demonstrating that 2-AP inhibited selective macrophage genes. The differential sensitivity to 2-AP suggested that the expression of a functional PKR may be required for the macrophage tumoricidal response triggered by LPS and IFN-alpha beta but not IFN-gamma. PMID- 7995953 TI - Functional characterization of the rat chemokine KC and its importance in neutrophil recruitment in a rat model of pulmonary inflammation. AB - Expression of mRNA for the neutrophil (PMN) chemokine, KC, in rat models of lung injury suggests a role for this chemokine in pulmonary inflammation. We addressed this hypothesis at the protein level by functionally characterizing recombinant rat KC (rKC) in vitro and in vivo. In vitro, rKC induced PMN chemotaxis and increased the expression of CD11b/CD18 on PMNs. Recombinant KC also induced a respiratory burst (quantitated by flow cytometry) in rat PMNs, similar to that caused by its human structural homologue, gro/melanoma growth-stimulating activity, on human PMNs, but less than that caused by IL-8 on human PMNs. Intratracheal instillation of rKC induced dose-dependent PMN influx into airspaces (average PMNs in bronchoalveolar lavage: vehicle = 1.5%, n = 4; rKC (1 microgram) = 11.5%, n = 2; rKC (10 micrograms) = 77.3%, n = 2). A neutralizing anti-KC Ab reduced the chemotactic activity of rat bronchoalveolar lavage fluid collected after the intratracheal administration of LPS (48.3 +/- 8% of control, n = 4). Anti-KC neutralizing Ab markedly inhibited PMN accumulation (71 +/- 6%) within the lungs in response to an intratracheal challenge of LPS. We conclude that rat KC is a major but not exclusive mediator of PMN activation and recruitment during LPS-induced pulmonary inflammation. PMID- 7995955 TI - Constitutive expression of human hsp27, Drosophila hsp27, or human alpha B crystallin confers resistance to TNF- and oxidative stress-induced cytotoxicity in stably transfected murine L929 fibroblasts. AB - Hyperthermia and other forms of stress that induce and/or stimulate heat shock or stress protein (hsp) expression enhance the cellular resistance to TNF-alpha. One of the stress proteins, hsp70, has been shown to participate in the molecular mechanisms that regulate this phenomenon. Here we have tested the capability of small hsps from different species to protect against this cytokine in the TNF sensitive L929 fibrosarcoma cells. The genes that encode human hsp27, Drosophila hsp27, and human alpha B-crystallin were placed under the control of the constitutive SV40 early promoter and were stably introduced into L929 cells. We observed that all clones that constitutively expressed the exogenous small hsps exhibited a strong protection against TNF-mediated killing, which was proportional to the level of the expressed proteins. This phenomenon did not correlate with altered binding of TNF-alpha to its receptors, and no protection was observed as a consequence of the transfection or selection procedures. In addition, the overexpression of the exogenous small hsps did not modify the level of the endogenous stress proteins in the transfected clones. Remarkably, the small hsps also induced a protection against oxidative stresses generated by either hydrogen peroxide or menadione. In L929 cells, the killing induced by TNF alpha and oxidative stress is thought to occur through the accumulation of intracellular reactive oxygen intermediates. Hence, our data suggest that the small hsps from different species share the property to protect L929 cells against the deleterious effects of reactive oxygen intermediates generated by either TNF-alpha or oxidative stress. PMID- 7995956 TI - Ig-binding surface proteins of Streptococcus pyogenes also bind human C4b-binding protein (C4BP), a regulatory component of the complement system. AB - Streptococcus pyogenes, an important human pathogen, expresses several proteins that interact with the immune system of the host. Among the proteins isolated from different bacterial strains are antiphagocytic M proteins, Ig Fc-binding proteins and exotoxins that act as superantigens. Here we report a novel interaction between S. pyogenes and the human immune system, the ability of most S. pyogenes strains to bind human C4BP (C4b-binding protein), a 570-kDa serum protein that inhibits the classical pathway of complement activation. Molecular analysis of three different streptococcal strains demonstrated that C4BP binds to protein Arp or protein Sir, two Ig-binding cell surface molecules that are members of the M protein family. These bacterial proteins have separate high affinity binding sites for Ig and for C4BP, as demonstrated by inhibition tests and binding assays with purified components. A single streptococcal cell surface molecule, Arp or Sir, therefore combines the abilities to bind Ig and C4BP, two high m.w. components of the immune system. Two bacterial strains expressing Arp or Sir were shown to selectively bind C4BP in whole human serum, suggesting that S. pyogenes also binds C4BP in the infected host. When bound to streptococcal cells, C4BP retained its ability to act as a cofactor in the degradation of C4b by factor I. These results indicate that many strains of S. pyogenes interfere with the classical pathway of complement activation by binding C4BP to the bacterial cell surface. PMID- 7995958 TI - Enhanced production of TGF-beta by blood monocytes from patients with active tuberculosis and presence of TGF-beta in tuberculous granulomatous lung lesions. AB - The expression of TGF-beta, a molecule that affects both immune responsiveness and wound healing, was examined in blood monocytes and granulomatous lesions from patients with active pulmonary tuberculosis. The spontaneous release of TGF-beta was higher in culture supernatants of monocytes from patients as compared with those of healthy subjects by an ELISA (p < 0.0005). TGF-beta activity was also confirmed in a bioassay in supernatants from patients. Next, freshly isolated monocytes from patients with tuberculosis and matched subjects were examined for TGF-beta activity. Cytosmears of monocytes were stained with an Ab against TGF beta 1 (anti-LC) or isotype-specific Ab by using an alkaline-phosphatase anti alkaline phosphatase method. In contrast to monocytes from healthy individuals, 60 to 70% of monocytes from patients demonstrated cytoplasmic staining for TGF beta (n = 3). Upon hypotonic lysis, monocytes from patients with tuberculosis contained immunoreactive TGF-beta (n = 3). By Northern blot analysis, monocytes from three of seven patients with tuberculosis had increased expression of TGF beta mRNA as compared with concurrently examined monocytes from healthy subjects. Within the granulomas of lung sections from two patients with untreated tuberculosis, TGF-beta immunoreactivity was identified in the Langhan's giant cells mainly and to a lesser extent the epithelioid cells using anti-LC Ab and the peroxidase-anti-peroxidase technique. Thus, both blood monocytes and lung granuloma macrophages from patients with active tuberculosis express TGF-beta. Excess activity of this cytokine in blood monocytes may underlie the depressed T cell responses of patients with tuberculosis. Moreover, within the infected tissues excess TGF-beta activity may interfere with anti-mycobacterial mechanisms and effective granuloma formation. PMID- 7995957 TI - HIV-1-specific cytotoxic T lymphocyte responses in the first year of life. AB - HIV-1-specific CTL responses were prospectively evaluated in infants born to HIV 1-seropositive women to assess the capability of the young infant to generate HIV 1-specific CTL and to examine the potential role of HIV-1-specific CTL in the pathogenesis of vertical infection. Our results indicate that some young infants, and even the fetus, seem to be capable of generating virus-specific CTL responses. The detection of HIV-1-specific CTL responses varied among infants, however, with respect to timing, HIV-1 gene product recognition, and the magnitude of detectable responses; HIV-1-specific CTL responses were uncommonly detected in the first few months of life. The less consistent detection of HIV specific CTL in early infancy contrasts with reports of the detection of HIV-1 specific CTL soon after primary infection in adults. HIV-1-specific CTL were not detected in any uninfected infants born to HIV-1-seropositive women. This description of HIV-1-specific CTL in infants may have important implications for understanding the pathogenesis of vertical HIV-1 infection and for the development of a vaccine to interrupt vertical infection. PMID- 7995959 TI - Induction of peptide-specific CD8+ CTL clones in beta 2-microglobulin-deficient mice. AB - We have examined the ability of beta 2-m- mice to produce CD4-8+ T cells by generating CD8+ CTLs to a defined ligand. We report here the first demonstration of peptide-specific, self-class I MHC-restricted CTLs from beta 2-m-deficient mice. We have used the KOD mouse, an H-2d beta 2-m- strain, to generate CTLs that recognize the class I MHC molecule Ld in association with one of two Ld-binding immunogenic peptides. Testing of these CTLs on a panel of Ld-binding peptides reveals a high degree of peptide specificity. Peptide-specific CTL bulk cultures from KOD mice differ from those generated in beta 2-m+ mice in that they possess altered affinities for their peptide ligands. In addition, we show that CTLs generated from beta 2-m- mice in the presence of beta 2-m+ stimulator cells and exogenous peptide are specific either for the exogenous peptide or for endogenous peptides that are present in association with Ld on the surface of beta 2-m+ cells, but are not present at detectable levels on beta 2-m- cells. These results demonstrate that positive selection of CD8+ CTLs can occur in vivo on the very low levels of class I MHC found in the KOD mouse. Furthermore, CTLs from the KOD mouse maintain a high degree of peptide specificity despite reduced levels of class I MHC. PMID- 7995960 TI - Regulation of cAMP-responsive enhancer binding proteins during cell cycle progression in T lymphocytes stimulated by IL-2. AB - IL-2 stimulates the proliferative response of various lymphoid cells. Previous studies showed an increase in intracellular levels of cAMP concomitant with an increase in phosphorylation of discrete proteins by protein kinase A at late G1 phase in mitogen-stimulated lymphocytes. Thus, experiments were undertaken to study nuclear proteins that bind to the cAMP-responsive enhancer (CRE) in cloned T lymphocytes stimulated with IL-2. With the use of a 32P-labeled CRE consensus sequence in a DNA binding gel mobility shift assay, we showed that IL-2 stimulation resulted in the induction of two major DNA-protein complexes at late G1/S during the cell cycle. This binding was competed in a dose-dependent manner by a nonlabeled CRE oligonucleotide but was not competed by a nonlabeled AP-1 oligonucleotide. Rapamycin, a potent immunosuppressant, which arrests IL-2 stimulated T lymphocytes at G1/S, inhibited the IL-2-induced CRE binding activities concomitantly with inhibition of DNA synthesis. By using specific Abs in a gel mobility shift assay, we identified two known CREB/ATF transcription factors in the IL-2-induced CRE complexes: the CRE binding factor (CREB), and ATF1. The induction of CREB binding by IL-2 was not associated with an increase in its abundance but was associated with a major increase in CREB phosphorylation that was particularly prominent at late G1/S. However, we found that G1/S progression induced by IL-2 was not associated with an increase in the intracellular levels of cAMP. These results suggest that 1) the transcription factors CREB and ATF1 and possibly other CRE binding proteins may have an important role in the modulation of specific gene expression at G1/S during cell cycle progression induced by IL-2. 2) The involvement of these CRE binding transcription factors in IL-2-stimulated cells is regulated via a mechanism that is not cAMP dependent. PMID- 7995961 TI - Selective loss of NK cytotoxicity in antisense NK-TR1 rat LGL cell lines. Abrogation of antibody-independent tumor and virus-infected target cell killing. AB - We have shown that NK-TR1, a protein containing a cyclophilin-like domain, is associated with a receptor/triggering molecule on the surface of human large granular lymphocytes (1). In the present study, we have further defined the role of NK-TR1 in target cell recognition/killing by generating antisense NK-TR1 transfectants in the rat LGL cell line, RNK-16. Stable transfectants were identified by analyzing permeabilized cells with the anti-NK-TR1 mAb, 4F9. Transfectants with low levels of 4F9 staining showed drastically reduced levels of killing against three NK-susceptible target cell lines. Lytic activity against vaccinia virus-infected cell lines also was dramatically reduced. In contrast, transfected cells showing normal levels of NK-TR1 expression demonstrated normal killing of all target cells. The ability of all transfectants to form conjugates was identical to that observed with the wild-type RNK cell line. Lectin-dependent cytotoxicity, reverse ADCC via NKR-PI, and ADCC-mediated killing were comparable in both high or low NK-TR1 expressing clones, demonstrating that the lytic machinery was still intact. BLT-esterase activity, PF levels, and surface marker phenotype were not significantly affected. These results provide strong evidence that NK-TR1 is an essential element in a signaling pathway leading to MHC unrestricted killing of tumor and virus-infected cells. PMID- 7995962 TI - CD8+ T cells specific to the exogenous antigen. Mode of antigen recognition and possible implication in immunosuppression. AB - This study demonstrates and characterizes CD8+ T cells specific to the exogenous Ag, bovine alpha s1-casein. Purified CD8+ T cells from alpha s1-casein-primed lymph node cells proliferated well in response to an alpha s1-casein derivative, trypsin-digested alpha s1-casein. CD8+ T cell repertoire for the exogenous Ag was directly demonstrated in the primary culture condition. The intact alpha s1 casein primed the responding CD8+ T cells in vivo more efficiently than the tryptic alpha s1-casein; however, the in vitro proliferative response by the intact alpha s1-casein was weaker than that of the tryptic alpha s1-casein. CD8+ T cells recognized the exogenous Ag in association with MHC class I molecules as revealed by an Ab-blocking study. The major immunodominant region for the CD8+ T cells was mapped to region 136-151 of alpha s1-casein, and peptide 136-151 primed the responding CD8+ T cells but not any CD4+ T cells. Peptide 136-151 is the CD8+ T cell-specific determinant. Upon antigenic stimulation, the exogenous Ag specific CD8+ T cells produced a significant level of IFN-gamma, which has immune suppressive activity for IgE synthesis. Our study strongly implies that CD8+ T cells that proliferate and produce IFN-gamma in response to the exogenous Ag would play a vital role in Ag-specific immunosuppression. PMID- 7995963 TI - IL-12 activates IFN-gamma production through the preferential activation of CD30+ T cells. AB - CD30 is normally expressed by a subset (15 to 20%) of CD45RO+ T cells after activation by a variety of T cell stimuli and defines the principal IFN-gamma producing T cells subset. Inasmuch as the production of IFN-gamma is regulated by IL-2 and IL-12, we have examined the effects of these cytokines on the proliferation, induction, and function of CD30+ and CD30- T cell subsets. Upon isolation, CD30+CD25+ T cells exhibit high levels of baseline proliferation compared with CD30-CD25+ T cells. Neutralizing Abs specific for IL-2, IL-4, IL-6, or IL-12 had no effect on basal levels of proliferation in CD30+CD25+ T cells, whereas anti-IL-2 inhibited the basal proliferative activity of CD30-CD25+ T cells. The addition of exogenous rIL-12 to purified CD30+CD25+ and CD30-CD25+ T cells subsets induced significantly higher maximal levels of proliferation in the CD30+ subset, whereas rIL-2 supported comparable levels of maximal proliferation in each subset. The addition of rIL-2 to anti-CD3-activated PBMC increased the relative numbers of CD30+ T cells by expansion of CD30+ T cells, as opposed to recruitment of CD30+ T cells from the CD30- population. Furthermore, the development of the CD30+ T cell subset was inhibited by either anti-IL-2, anti-IL 12, or rIL-10. Inhibition by anti-IL-2 and rIL-10 was overcome by the addition of rIL-12, but not IL-2, to the cultures. Finally, rIL-12 increased IFN-gamma production by CD30+ T cells, yet had little effect on IFN-gamma production by CD30- T cells. Thus, CD30+ T cells are preferentially regulated by IL-12, and the effects of IL-12 on T cell IFN-gamma production are mediated largely through its effects on the CD30+ subset. PMID- 7995964 TI - [Isolated retrovesical hydatid cyst. Apropos of two cases]. AB - Isolated retrovesical location of hydatid cyst is a very uncommon condition. Clinical patterns appear after a long course of the cyst. They are represented by hypogastric mass associated with compressive manifestations. Ultrasonography is essential for diagnosis and identification of other sites. When diagnosis is unclear, then CT scan plays a role. Cystectomy and pericystic resection, as extensive as possible, is the adequate treatment that gives successful results in most cases. PMID- 7995965 TI - [Epidermoid cyst of the testis. Apropos of a case]. AB - The epidermoid cyst of the testis, a rare and benign tumour, continues to create problems. Its definitive diagnosis remains a histopathological one and alters the prognosis and therapy. Based on their case report and a literature review, the authors discuss the different diagnostic, prognostic and therapeutic aspects of this lesion. PMID- 7995966 TI - [Ureteral stenosis caused by pelvic actinomycosis]. AB - The authors report a case of pelvic actinomycosis causing ureteral obstruction in a 30-year-old woman. An intra-uterine device being in place for 6 years is considered as the main cause. The treatment, which included a laparotomy for abscess drainage, an indwelling double pigtail ureteral stent and a 9 month antibiotherapy led to recovery after an initial relapse. PMID- 7995967 TI - [Treatment of hypospadias apropos of 557 cases. Evolution of techniques in a care unit of pediatric surgery in a period of 18 years, and current indications]. AB - The authors report their experience with surgical treatment of hypospadias about 557 cases. From 1974 to 1981, only 84 cases were cured by classical procedures (Mathieu, Van der Meulen, Perlemutter, Duplay-Fevre, Leveuf-Cendron), sometimes with Cahuzac uretroplasty). The age when correction depended from the type of hypospadias and several times were after necessary. From 1981 to 1992, 463 cases were operated, always between 18 month to two years of age, with only one operative with therapeutic indications are actually such proposed: distal meatotomy or modified MAGPI procedure for glandular hypospadias; Duplay uretroplasty for coronal form; Mathieu or onlay island flap for anterior and medial penil types without curvature; Mollard or Duckett uretroplasty for penil forms with chordee; Then, for posterior types, complementary posterior Duplay uretroplasty, or vesical ou buccal grafts. PMID- 7995968 TI - [Technique of total prostatectomy for cancer. The experience of ANFUC (National Association of Continuous Urologic Education)]. AB - The members of the ANFUC performed 1,094 total prostatectomies via the hypogastric route in patients with cancer of the prostate. An analysis and discussion of the technique is presented. PMID- 7995969 TI - [Uro-oxalic renal lithiasis. Special aspects]. AB - In a paper published in 1974, it was reported that uro-oxalic stones are found more often in subjects with group O than with group A blood types although the proportions of these two blood types are approximately equivalent in the French population. The present work confirms these data, the ratio of group O to group A renal lithiasis being approximately 3 to 1. In a paper published in 1987, uro oxalic stones were found to occur preferentially on the left side: 84 on the left and 39 on the right. The present work confirms this notion since in 57 cases, stones were bilateral in 2 cases, on the left in 39 and on the right in 16. Extra corporeal shock wave lithotripsy was performed in 40 of the 57 cases and showed that uro-oxalic stones are more resistant to shock-waves than the other types of stones. They are about as hard as calcium oxalate monohydrate stones or harder in certain cases: A mean of 3,865 shock-waves were required in the 40 cases of the uro-oxalic lithiasis treated with the HM3 Dornier device, while the mean number of shock-waves required for all types of stones in general varies from 2,000 to 2,500. In 4 cases, 5,000 or 6,000 high power shock-waves (7,000 in one session and 9,500 in two sessions) had to be used to obtain a satisfactory result. The calcium oxalate part of these stones is almost always composed of calcium oxalate monohydrate.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7995970 TI - [Valves of the posterior urethra in newborns, infants and children. Apropos of a series of 60 cases]. AB - The authors report their experience with posterior valves of the urethra in children. Sixty patients were seen from 1982 to 1991. The problems of diagnosis and therapy of particular importance in poor countries are emphasized. PMID- 7995971 TI - Tethered cord syndrome in adult. A rare presentation. AB - A 21 year-old female presented with acute renal failure and bilateral uretero vesical junction obstruction. After percutaneous drainage of the upper tracts, the renal function returned to a baseline serum creatinine of 2.6 mg/dl. The initial evaluation supported a diagnosis of urinary tuberculosis and a triple drug therapy was instituted. Further reevaluation revealed the presence of a neurogenic bladder secondary to a lumbar intradural lipoma associated with a thick filum terminale and a myelomeningocele. Tethered cord syndrome in adult is extremely rare and is classically responsible for urological, orthopedic and neurological dysfunctions. This isolated urological presentation with no significant associated neurologic deficits is unique and prompted this report, with a review of the current understanding and management of adult tethered cord syndrome. PMID- 7995972 TI - [Giant adenoma of the kidney. Apropos of a case with 7 years follow-up]. AB - The authors report one case of giant kidney adenoma. They describe the radiological and histological aspects of this rare tumor. Prognosis and treatment. PMID- 7995973 TI - Genotyping of human T cell lymphotropic virus type I using Australo-Melanesian topotype-specific oligonucleotide primer-based polymerase chain reaction: insights into viral evolution and dissemination. AB - Sequence variants of human T cell lymphotropic virus type I (HTLV-I), genetically distinct from cosmopolitan strains of HTLV-I from Japan, the Americas, the Caribbean, and Africa, have been discovered among Melanesians in Papua New Guinea and the Solomon Islands and among Australian aboriginals. By using oligonucleotide primer pairs derived from sequences unique to the gp46- and gp21 encoding regions of the env gene of the Melanesian HTLV-I variants, HTLV-I strains from widely separated geographic regions could be grouped into either of two major geographic-specific genotypes or topotypes: Australo-Melanesian and cosmopolitan. These primers did not permit amplification of the corresponding env gene regions in strains of simian T cell lymphotropic virus type I from Asia and Africa. Phylogenetic analysis also supported two distinct lineages, consistent with evolution of HTLV-I in Australia and Melanesia independent from that in other parts of the world. PMID- 7995974 TI - MT-2 cell tropism of human immunodeficiency virus type 1 isolates as a marker for response to treatment and development of drug resistance. AB - The correlation of the tropism of human immunodeficiency virus type 1 (HIV-1) isolates for MT-2 cells with response to zidovudine and didanosine treatment and with development of drug resistance was studied. Patients with MT-2-negative but not MT-2-positive HIV-1 had a significant increase in CD4+ lymphocyte counts during the first 6 months of treatment. In both groups and for both drugs, the rate of CD4+ lymphocyte decline decreased after the start of treatment. MT-2 positive isolates were more likely than MT-2-negative isolates to show reduced sensitivity to zidovudine and didanosine. Because the differences in zidovudine sensitivity were first evident after 12 months of treatment, drug resistance was probably not the cause of poor response early in zidovudine treatment in patients with MT-2-positive HIV-1. Thus, patients with MT-2-positive virus have limited benefit from treatment with single nucleoside analogues. Knowledge of MT-2 cell tropism may be important in clinical trials and for choosing treatments for patients. PMID- 7995975 TI - Spontaneous in vitro anti-human immunodeficiency virus type 1 antibody secretion by peripheral blood mononuclear cells is related to disease progression in zidovudine-treated adults. AB - As part of a continuous search for surrogate markers of therapeutic efficacy in AIDS, spontaneous in vitro production by peripheral blood mononuclear cells of antibody to human immunodeficiency virus type 1 (HIV-1) was investigated in 50 HIV-1-infected adults. It was independent of CD4+ cell counts, p24 antigenemia, serum beta 2-microglobulin concentration, and clinical status of the patients. The effect of zidovudine on this antibody secretion and the appearance of signs or symptoms of HIV-1 disease progression were evaluated in 20 patients over 24 weeks. Anti-HIV-1 antibody secretion decreased significantly (P = .002) as of the first month of zidovudine treatment only in the 13 HIV-1-infected patients without disease progression. This is earlier than the occurrence of variations in CD4+ cell count and serum beta 2-microglobulin concentration. These results suggest that in vitro antibody production could be a surrogate marker for evaluation of the in vivo antiretroviral efficacy of zidovudine, even in p24 antigen-negative patients. PMID- 7995976 TI - A phase I/IIA clinical study with a chimeric mouse-human monoclonal antibody to the V3 loop of human immunodeficiency virus type 1 gp120. AB - A phase I/IIA clinical trial with the chimeric mouse-human monoclonal antibody CGP 47,439 to the principal neutralization determinant in the V3 region of human immunodeficiency virus type 1 (HIV-1) strain IIIB envelope protein gp120 is reported. The trial was an uncontrolled single-center, open-label, multidose tolerability, immunogenicity, and pharmacokinetic study in homosexual men with advanced HIV disease. Patient groups were formed on the basis of the reactivity of the antibody with the gp120 of their HIV-1 isolates. Intravenous infusions of 1, 10, and 25 mg of antibody were followed by seven escalated doses of 50, 100, and 200 mg, every 3 weeks. The antibody was well tolerated; no toxicity was observed. Some patients showed a transient but insignificant antibody response to the antibody with no apparent adverse reactions or accelerated elimination of it. Substantial serum levels of the antibody were maintained with a mean t1/2 beta of 8-16 days. A virus burden reduction was observed in some patients. PMID- 7995977 TI - Relationship between plasma concentrations of 3'-deoxy-3'-fluorothymidine (alovudine) and antiretroviral activity in two concentration-controlled trials. AB - Two concentration-controlled trials (CCTs) defined the relationship between plasma concentrations of 3'-deoxy-3'-fluorothymidine (alovudine) and changes in surrogate markers of antiretroviral activity. In an initial open-label CCT involving 14 subjects infected with human immunodeficiency virus (HIV), unacceptable hematologic toxicity occurred when the area under the concentration time curve during a 12-h dosing interval (AUC12) was > or = 300 ng*h/mL. Consequently, 46 subjects were assigned to AUC12s of 50, 100, or 200 ng*h/mL for up to 16 weeks in a prospective, randomized, double-blind CCT. Alovudine caused a concentration-dependent reduction in p24 antigen and peripheral blood mononuclear cell HIV titers within 4 weeks of start of treatment. The AUC12 producing a 50% reduction in p24 (108 ng*h/mL) had a trough concentration identical to the reported IC50 of alovudine in HIV-infected H9 cells. It may be possible to predict the antiretroviral activity of certain nucleoside analogues as a function of plasma drug concentration. PMID- 7995979 TI - Incidence and prevalence of human immunodeficiency virus, hepatitis B virus, hepatitis C virus, and cytomegalovirus among health care personnel at risk for blood exposure: final report from a longitudinal study. AB - In a 10-year dynamic cohort study, 976 health care providers were followed a mean of 1.9 years to evaluate the risk of human immunodeficiency virus (HIV) transmission, delayed seroconversion, and seronegative latent infection following occupational exposures. The seroprevalence and incidence of HIV, hepatitis B virus (HBV), hepatitis C virus (HCV), and cytomegalovirus (CMV) infection were also measured, with annual serologic testing for viruses and postexposure HIV tests. One of 327 percutaneous exposures (0.31%; confidence interval, 0.008% 1.69%) and 0 of 398 mucocutaneous exposures to HIV-infected blood transmitted HIV. Neither delayed seroconversions nor seronegative latent infections were detected. The baseline seroprevalences of HBV, HIV, HCV, and CMV infection were 21.7%, 0, 1.4%, and 43.4%, respectively. Corresponding incidence density rates were 3.05, 0.055, 0.08, and 2.48 (per 100 person-years). Despite infection control precautions and availability of hepatitis B vaccine, these health care providers remain at risk for acquiring bloodborne viral infections. PMID- 7995980 TI - Outcome of perinatal hepatitis B virus exposure is dependent on maternal virus load. AB - To evaluate the role of maternal hepatitis B virus (HBV) DNA levels in perinatal infection, two nested case-control studies were done within a cohort of 773 hepatitis B surface antigen (HBsAg)-positive Taiwanese women and their infants. As serum HBV DNA levels increased from < 0.005 to > or = 1.4 ng/mL among the hepatitis B e antigen (HBeAg)-positive mothers, the odds ratio (OR) for having a persistently infected infant increased from 1.0 to 147.0 (P for trend < .001). Among HBeAg-negative mothers, the OR for having a persistently infected infant was 19.2 (95% confidence interval, 2.3-176.6) in mothers with high versus low levels of serum HBV DNA. A logistic regression analysis identified maternal HBV DNA to be a stronger independent predictor of persistent infection than HBeAg status. Thus, perinatal exposure to high levels of maternal HBV DNA is the most important determinant of infection outcome in the infant. PMID- 7995978 TI - Risk factors for squamous intraepithelial lesions on Pap smear in women at risk for human immunodeficiency virus infection. AB - To determine risk factors for squamous intraepithelial lesions (SIL) on Pap smear, 253 women at risk for human immunodeficiency virus (HIV) infection had Pap smear, HIV antibody testing, CD4+ cell measurements, and human papillomavirus (HPV) genome detection by Southern blot hybridization. Associated with SIL (P < .05) on univariate analysis were genital HPV (SIL prevalence in HPV-positive subjects, 36.3%; odds ratio [OR], 9.3; 95% confidence interval [CI], 4.2-20.3) and HIV infection (SIL prevalence in seropositive subjects, 21.9%; OR, 2.5; 95% CI, 1.2-5.1). No demographic or behavioral variables were associated with risk for SIL. Multivariate analyses identified genital HPV infection (OR, 6.78; 95% CI, 2.9-15.7), detection of known high-risk HPV types (OR, 11.8; 95% CI, 4.1 34.1), strong HPV Southern blot signal strength (OR, 10.8; 95% CI, 3.5-33.7), and severe HIV-related immunosuppression (OR, 3.1; 95% CI, 1.04-9.5) as independent risk factors associated with SIL. Thus, severe immunosuppression due to HIV infection increases the risk for SIL mediated by HPV infection. PMID- 7995981 TI - Presence of antibodies to seven human papillomavirus type 16-derived peptides in cervical cancer patients and healthy controls. AB - Sera from 133 cervical cancer patients and 154 healthy women (controls) from Spain and Colombia were tested in IgG-specific ELISAs for the presence of antibodies against seven peptides derived from five open-reading frames of human papillomavirus (HPV) type 16. Three of the peptides corresponded to overlapping regions of the N-terminal half of E7 protein; the other peptides corresponded to selected regions of E2, E4, L1, and L2 proteins. The prevalence of antibodies against E2 and E7 peptides was significantly different between patients and controls. The most marked differences were for E7 peptides. HPV DNA polymerase chain reaction diagnoses of cervical scrapes were available; these were correlated with serologic findings. In HPV-16 DNA-positive patients, E7 antibodies were more broadly and more strongly reactive than in other patient groups. PMID- 7995982 TI - Nonimmunoselected intrastrain genetic variation detected in pairs of high yielding influenza A (H3N2) vaccine and parental viruses. AB - Seven influenza A (H3N2) high-yielding vaccine candidate strains were examined. Antigenic analysis revealed that 5 of the strains could be distinguished antigenically from their corresponding wild type parent viruses. Comparative sequence data for the HA1 domains of the HA (hemagglutinin) genes for these 5 high-yielding viruses and the corresponding wild type parents demonstrated one to three amino acid substitutions within each virus pair, with at least one amino acid change being located in a previously defined antigenic site. Comparison of the HA sequences of the 2 antigenically indistinguishable virus pairs revealed no amino acid differences in 1 and one amino acid change in the other. Examination of 1 additional wild type virus, A/Guangdong/39/89, and its three high-yielding derivatives obtained either by serial egg passage or by reassortment revealed an additive effect of the HA and M genes in creating the high-yielding phenotype. PMID- 7995983 TI - Epstein-Barr virus gp350-specific antibody titers and antibody-dependent cellular cytotoxic effector function in different groups of patients: a study using cloned gp350-expressing transfected human T cell targets. AB - An NK cell activity-resistant human lymphoid T cell line (CEM-NKr) expressing the transfected Epstein-Barr virus (EBV) gp350 gene was used in membrane immunofluorescence (MIF) and antibody-dependent cellular cytotoxicity (ADCC) assays to analyze the gp350-specific humoral and ADCC responses in groups of EBV seropositive persons. Results show that there is no correlation between gp350 specific ADCC-mediating antibody titers and MIF or EBV neutralizing antibody titers. For example, sera from patients in the acute phase of infectious mononucleosis, while positive by MIF assay or EBV neutralization test, were not reactive in the ADCC assay. Results also show that nasopharyngeal carcinoma (NPC) patients on MIF present high IgG titers against gp350 compared with healthy persons. Anti-gp350 IgA antibodies were detected in all groups tested; however, titers were highest in the NPC group. PMID- 7995984 TI - A live attenuated dengue-1 vaccine candidate (45AZ5) passaged in primary dog kidney cell culture is attenuated and immunogenic for humans. AB - A dengue-1 candidate vaccine (45AZ5), previously found to be underattenuated in 2 volunteers, was further attenuated by passage in primary dog kidney (PDK) cell cultures. New candidate vaccines prepared from three levels of PDK-passaged virus, PDK-10, PDK-20, and PDK-27, were each injected into 9 or 10 volunteers. There was a significant, progressive decline in viremia, clinical illness, and hematologic changes from low to high PDK cell passage level. PDK-20 infected all 10 vaccinees and induced viremia in 5, transient fever in 3, symptoms that resulted in curtailed activities for < or = 1 day in 4, and neutralizing antibody in all 10, which persisted for > or = 1 year in 5 of 8 vaccinees tested. Progressive passage in PDK cell culture progressively attenuates vaccine candidate strain 45AZ5 for humans. Because passage level PDK-20 may be suitable for healthy adults at high risk of dengue fever, additional clinical trials of this strain are warranted. PMID- 7995986 TI - Analysis of circulating phagocyte activity measured by whole blood luminescence: correlations with clinical status. AB - The present study was undertaken to determine if measurement and analysis of phagocyte function are useful for diagnosis and staging of infection. Circulating phagocyte activity was measured in healthy volunteers and sequentially in patients with acute infections of different types and severity, including those with diabetes mellitus or human immunodeficiency virus (HIV) infection. Using an automated luminescence system, these phagocyte functions were measured in whole blood: basal and phorbol 12-myristate 13-acetate (PMA)-stimulated oxidase activity, basal and PMA-stimulated simple dioxygenation (e.g., oxidase-driven haloperoxidase activity), and circulating and primed opsonin receptor-dependent dioxygenation. Multiple discriminant analysis of these data showed significant differences between healthy controls, diabetic patients, HIV-positive subjects, and patients with pneumonia or sepsis syndromes. Longitudinally, circulating phagocyte function correlated with clinical condition, severity of infection, and outcome. This methodology provides rapid, objective, and sensitive diagnostic and monitoring information for patients with infections. PMID- 7995985 TI - Genetic identification of a new Puumala virus strain causing severe hemorrhagic fever with renal syndrome in Germany. AB - A severe case of suspected hemorrhagic fever with renal syndrome (HFRS) was recently identified in northwestern Germany. A genetic detection assay was designed that identified hantavirus-specific RNA in the patient's clinical specimens by reverse transcriptase-polymerase chain reaction amplification of virus S and M genome segments. Phylogenetic analysis of the nucleotide sequences demonstrated that this virus belonged to the Puumala (PUU) group, with the closest relationship to a PUU isolate from Finland. Within the group, this virus formed a separate lineage. This finding represents the first genetic characterization of a hantavirus causing severe HFRS in Germany. The data suggest that PUU viruses circulating in western European countries are genetically distinct from their northeastern counterparts. Comparison of deduced amino acid sequences demonstrated a loss of a potential N-glycosylation site in the G2 protein compared with other PUU viruses. PMID- 7995987 TI - Protective effects of an N-terminal fragment of bactericidal/permeability increasing protein in rodent models of gram-negative sepsis: role of bactericidal properties. AB - Effects of an N-terminal fragment of bactericidal/permeability increasing protein (rBPI21) on bacterial infections were determined. Intravenous (i.v.) rBPI21 increased survival and reduced bacteremia in rats after an iv injection of Escherichia coli O7:K1 bacteria. rBPI21 inhibited the rise in tumor necrosis factor-alpha resulting from challenge with 2 strains of E. coli. Intraperitoneal (ip) injection of rBPI21 increased survival of mice after ip injection of E. coli O7:K1 and Pseudomonas aeruginosa and reduced bacteria in peritoneal lavage fluid and blood and inhibited cytokine production in response to E. coli. rBPI21 alone did not protect mice challenged with E. coli O111:B4 but was protective and reduced bacterial counts when administered in combination with the antibiotic cefamandole. The data show that protection with rBPI21 is associated with reductions in bacterial counts and is enhanced by antibiotics. Bactericidal activity, in addition to antiendotoxin activity, is involved in the efficacy of rBPI21 in models of gram-negative infection. PMID- 7995988 TI - Characterization of two monoclonal antibodies directed against bactericidal/permeability-increasing protein. AB - In this study the production and characterization of two monoclonal antibodies (MAbs), 4E3 and 5D7, against the bactericidal/permeability-increasing protein (BPI) were described. Using ELISAs, both 4E3 and 5D7 were shown to detect recombinant (r) BPI. Furthermore, natural BPI present in polymorphonuclear leukocytes (PMNL) was detected by both 4E3 and 5D7. The use of both MAbs in flow cytometry revealed that PMNL expressed low levels of cell-surface BPI. Lipopolysaccharide (LPS) was shown to block the interaction between anti-BPI MAb and rBPI. In addition, the MAbs blocked biologic activity of rBPI. The inhibition by BPI of LPS activation of the limulus amebocyte lysate assay and of LPS-induced tumor necrosis factor-alpha release by monocytes was prevented by 4E3 and 5D7. Both MAbs are specifically directed against BPI and can inhibit BPI bioactivity. PMID- 7995989 TI - Synthetic peptides that mimic the binding site of horseshoe crab antilipopolysaccharide factor. AB - Tachypleus antilipopolysaccharide (LPS) factor (TALF) is a protein of 102 amino acids in the lysate of amebocytes of Tachypleus tridentatus that binds bacterial LPS with high affinity and blocks its biologic activity in numerous assays. To elucidate the minimal sequences that bind LPS, overlapping synthetic peptides based on the sequence of TALF were assessed for the ability to bind and neutralize LPS. TALF41-53 was the minimal sequence that bound LPS, as assessed by a slot blot capture assay. TALF29-59 bound LPS with the highest potency. TALF29 59 decreased LPS-induced coagulation of limulus amebocyte lysate, induction of cytokines from human monocytes, and LPS-induced lethality in sensitized mice. Synthetic peptides based on TALF or other LPS-binding proteins may be useful for the design of drugs for treatment of endotoxemia. PMID- 7995990 TI - Intestinal kinetics and dynamics of Escherichia coli heat-stabile enterotoxin in suckling mice. AB - The heat-stabile enterotoxin produced by Escherichia coli (ST) induces diarrhea by binding to receptors on intestinal cells, activating guanylyl cyclase, and increasing cyclic GMP. High- and low-affinity receptors for this toxin have been identified previously. ST induces intestinal secretion in suckling mice in picomole doses, suggesting a role for high-affinity receptors in this process. The present studies examine the relative roles of high- and low-affinity receptors in this process. The time course of changes in free ST concentrations in suckling mouse intestine was determined after intragastric inoculation. Also, binding characteristics of high- and low-affinity receptors and their coupling to guanylyl cyclase were defined in intestinal membranes from suckling mice. Intestinal concentrations of toxin and receptor binding characteristics empirically determined were used in a dynamic model correlating fractional occupancy of high- and low-affinity receptors with intestinal secretion to estimate their relative contributions to ST-induced diarrhea. PMID- 7995991 TI - Cytokine production patterns and lymphoproliferative responses in volunteers orally immunized with attenuated vaccine strains of Salmonella typhi. AB - New recombinant strains of attenuated Salmonella typhi used as live oral vaccines elicit potent immune responses. This study examined the patterns of cytokine production and proliferation to specific S. typhi antigens in subjects orally immunized with attenuated S. typhi vaccines CVD 906, CVD 908, and CVD 908 expressing the circumsporozoite protein of Plasmodium falciparum. After immunization, sensitized lymphocytes were found in subjects' blood that exhibited significantly increased proliferative responses and interferon-gamma production to purified S. typhi flagella when compared with preimmunization levels. Significant negative correlations were observed between interleukin-4 production and both interferon-gamma production and proliferation to S. typhi flagella. These results demonstrate that oral immunization with attenuated S. typhi strains alone or with those carrying a foreign gene elicits strong systemic cell-mediated immunity to purified S. typhi antigens, including the production of cytokines compatible with T1-type responses. PMID- 7995992 TI - Development of a live, oral, attenuated vaccine against El Tor cholera. AB - Vibrio cholerae El Tor strains from Peru, Bangladesh, and Bahrain were attenuated by deletion of a genetic element that encodes virulence factors and RS1. The B subunit of ctx (ctxB) was reintroduced into the recA gene of the deletion mutants, rendering them unable to recombine with exogenous genetic elements and generating Peru-3, Bang-3, and Bah-3. Fifteen volunteers received one dose of various vaccine strains at 4 x 10(6) to 1 x 10(8) cfu. All strains colonized the gut. A > or = 4-fold rise in vibriocidal titer was observed in 14 volunteers, with titers of > or = 1600 in 13. Peru-3 was the least reactogenic, but 2 of 6 volunteers had loose stools. Peru-14, a filamentous motility-deficient mutant of Peru-3, was well tolerated and colonized 18 of 21 volunteers at doses of 2 x 10(6) to 1 x 10(9) cfu. Also, when 8 Peru-3 or Peru-5 vaccinees, 5 Peru-14 vaccinees, and 8 controls were challenged with 2 x 10(6) cfu V. cholerae El Tor Inaba (N16961), 11 vaccinees were protected compared with no controls. Peru-14 shows promise as a safe, effective, single-dose oral vaccine against El Tor cholera. PMID- 7995993 TI - Peptidoglycan isolated from nontypeable Haemophilus influenzae induces experimental otitis media in the chinchilla. AB - Bacterial cell wall components induce a number of biologic effects and promote inflammatory changes in a variety of hosts. Peptidoglycan isolated from Streptococcus pneumoniae can induce inflammation in the middle ear; however, an analogous role for peptidoglycan derived from gram-negative otitis media pathogens has not been described. Peptidoglycan isolated from nontypeable Haemophilus influenzae (NTHi), a major cause of otitis media, was evaluated in a chinchilla model. The direct injection of the middle ear with 3-300 micrograms of peptidoglycan resulted in tympanic membrane inflammation, abnormal pressure in the middle ear, leukocytosis, and histopathologic changes in the middle ear mucosa that included marked edema, osteoneogenesis, focal hemorrhage, and a mononuclear infiltration into the subepithelial space. These data indicate that NTHi peptidoglycan induced inflammation and histopathologic changes in the tympanic membrane and middle ear mucosal epithelium and may contribute to the pathogenesis of otitis media. PMID- 7995994 TI - IS6770, an enterococcal insertion-like sequence useful for determining the clonal relationship of clinical enterococcal isolates. AB - Enterococci expressing resistance to antimicrobial agents are increasingly important nosocomial pathogens. Effective strategies to prevent or abort outbreaks of resistant enterococcal infection will rely on an accurate understanding of the mechanisms by which these organisms spread. A 1065-bp insertion-like sequence (IS6770) is present in varying copy numbers in > 90% of enterococcal strains thus far examined. Hybridization patterns resulting from hybridization of enterococcal genomic DNA with an internal IS6770 probe vary considerably between unrelated strains and correlate well with results of pulsed field gel electrophoresis and field-inversion gel electrophoresis in identifying clonal relationships among enterococcal isolates. IS6770 analysis of several outbreaks of resistant enterococci has confirmed the spread of single resistant clones rather than the emergence of resistance within the resident flora. These results suggest that IS6770 hybridization will be a useful tool for tracing the epidemiology of nosocomial enterococcal infections. PMID- 7995995 TI - A plasmid-encoded surface protein on Enterococcus faecalis augments its internalization by cultured intestinal epithelial cells. AB - Aggregation substance, a plasmid-encoded Enterococcus faecalis surface protein, plays a role in mediating the formation of mating aggregates, resulting in plasmid transfer. The role of aggregation substance in the internalization of E. faecalis by cultured intestinal epithelial cells, namely HT-29 cells, was analyzed. It was associated with a significant increase in endocytosis of E. faecalis by HT-29 cells: Numbers of internalized enterococci were fewer than of an invasive strain of Listeria monocytogenes, similar to Salmonella typhimurium and another L. monocytogenes strain, and greater than relatively noninvasive strains of E. faecalis, Proteus mirabilis, and Escherichia coli. Electron microscopy confirmed aggregation substance on the surface of strains interacting with the enterocyte microvillous surface, and intracellular enterococci were localized within membrane-bound vacuoles in the enterocyte cytoplasm. Thus, aggregation substance may facilitate E. faecalis internalization by host epithelial cells. PMID- 7995996 TI - Response of human polymorphonuclear leukocytes and monocytes to Trichosporon beigelii: host defense against an emerging opportunistic pathogen. AB - To further understand human host defenses against Trichosporon beigelii, functional responses were investigated of polymorphonuclear leukocytes (PMNL) and elutriated human monocytes (EHM) to this opportunistic fungal pathogen. There was significantly less PMNL phagocytosis (P < .001) and killing (P < .001) of T. beigelii isolates than of Candida albicans. However, levels of superoxide anions generated by PMNL in response to T. beigelii and C. albicans were comparable. Pretreatment of PMNL with granulocyte colony-stimulating factor or interferon gamma (IFN-gamma) did not significantly enhance fungicidal activity. Killing of T. beigelii by EHM also was significantly impaired compared with killing of C. albicans (P < .001). However, pretreatment of EHM with macrophage colony stimulating factor, granulocyte-macrophage colony-stimulating factor, or IFN gamma all resulted in enhanced fungicidal activity. Thus, phagocytosis and killing of T. beigelii by PMNL and EHM are significantly less efficient than that of C. albicans. However, monocytes may be more important in the control of Trichosporon species than previously shown. PMID- 7995997 TI - Karyotyping of Candida albicans isolates obtained longitudinally in women with recurrent vulvovaginal candidiasis. AB - Ten women with recurrent vulvovaginal candidiasis (RVVC) due to Candida albicans were followed for a mean of 35.3 months, and 81 vaginal isolates were evaluated by pulsed-field gel electrophoresis for strain delineation. The initial strain of C. albicans isolated was unique to each patient; in addition, in 8 women, only 1 strain type of C. albicans was identified throughout follow-up. In 1 patient, 3 strains of C. albicans were identified over a 27-month period and in another, 2 strains were recovered over a 30-month period. Two pairs of women shared identical strains of C. albicans. These results confirm the enormous diversity of strain types of C. albicans and demonstrate the persistence of colonization with the same strain over prolonged periods despite therapy. Results also support the concept of recurrent vaginitis being due to vaginal relapse or endogenous reinfection with the identical strain. PMID- 7995998 TI - Antibodies inhibiting Trypanosoma cruzi trans-sialidase activity in sera from human infections. AB - Trans-sialidase, an enzyme that transfers sialic acid among macromolecules, has been implicated in invasion of host cells by Trypanosoma cruzi, the agent of Chagas' disease. Most antibodies produced in natural and experimental infections are directed to the highly antigenic C-terminal domain (shed acute-phase antigen). These antibodies do not inhibit the trans-sialidase activity, which is present in the N-terminal domain of the molecule. Antibodies able to inhibit trans-sialidase in sera from human infections have been found. TIA (trans sialidase inhibition assay) was positive in sera from patients with acute and chronic infections. Healthy and congenitally infected infants born to mothers with Chagas' disease were also TIA-positive, but the antibody titers diminished within months after birth or after treatment. Thus, antibodies neutralizing trans sialidase are detectable in most forms of T. cruzi human infections, and TIA may be useful in the diagnosis of Chagas' disease. PMID- 7995999 TI - Absence of precore stop mutant in chronic dual (B and C) and triple (B, C, and D) hepatitis virus infection. AB - Sequences of hepatitis B virus (HBV) precore regions from 7 patients with HBV and hepatitis C virus (HCV) dual infection and 2 with HBV, HCV, and hepatitis D virus (HDV) triple infection were analyzed. Two patients, 1 with only acute HBV infection and 1 with only chronic HBV infection, were also included for comparison. All patients had antibodies against HBV e antigen (anti-HBe) except 1 with chronic hepatitis B and C. No precore stop mutation at codon 28 (TGG to TAG mutation) was found in 21 cloned sequences from the 7 patients with HBV and HCV infection, nor in 11 cloned sequences from 2 patients with HBV, HCV, and HDV infection. However, mutations in other positions of the precore region were observed in 2 patients with hepatitis B and C. In both cases, precore sequences with mutations in different positions were obtained from the same serum sample. No mutations were observed in other positions of the precore region in the 2 patients with hepatitis B, C, and D. The presence of anti-HBe in these patients was probably due to the low level of HBV replication and not to the presence of the precore stop mutant. PMID- 7996000 TI - Neuroinvasion and persistence of human herpesvirus 6 in children. AB - Human herpesvirus 6 (HHV-6) causes a febrile illness in children and has been implicated as a cause of encephalitis and recurrent seizures. Paired samples of cerebrospinal fluid (CSF) and peripheral blood mononuclear cells (PBMC) from 487 children were evaluated by nested polymerase chain reaction (PCR) for evidence of current or past infection with HHV-6. PBMC were also cultured for isolation of HHV-6. These data were correlated with the patients' clinical information. HHV-6 DNA was detected in 72 (14.8%) of 487 CSF samples. HHV-6 persistence was documented in 142 children by PCR detection of HHV-6 DNA in PBMC or CSF (or both) in the absence of primary HHV-6 infection; the central nervous system was the only site of HHV-6 DNA persistence in 28.9%. HHV-6 DNA can be detected in the CSF of children during and after primary infection, and the central nervous system may be the sole site of persistence. PMID- 7996001 TI - Experimental transmission of hantavirus infection in laboratory rats. AB - This study found a competent transmission of hantavirus between cagemates using congenitally T cell-deficient Rowett nude rats (rnu/rnu). Intraperitoneally infected immunologically normal rats (rnu/+) did not transmit the hantavirus to their normal cagemates (rnu/+) but did to Rowett nude rats (rnu/rnu). Thus, nude rats were shown to be highly susceptible to the hantavirus infection. Also, infected nude rats (rnu/rnu) discharged the infectious viruses, to cause a prevalence of infection among normal cagemates (rnu/+). The infection system demonstrated here using Rowett rats (rnu/rnu) may provide a useful model to study the mechanism of the hantavirus infection. PMID- 7996002 TI - Decay of transplacental human immunodeficiency virus type 1 antibodies in neonates and infants. AB - Transplacental human immunodeficiency virus (HIV) antibodies from 11 uninfected and 3 infected infants of HIV-seropositive mothers were measured using end point titration of twofold dilutions of sera by a particle-agglutination method. Four or more sequential serum samples from each infant were collected between birth and age > or = 14 months and analyzed. Linear regression of log2 antibody titers of uninfected infants plotted against age (days) showed an exponential decay in maternal HIV antibodies. The mean half-life of passive HIV antibodies was 23.1 +/ SD 4.2 days (range, 18.2-29.3; 95% confidence interval, 20.2-26.0). The median age of clearance of maternal HIV antibodies was 13.3 months (range, 10.4-15.6). A model assuming first-order exponential decay and production of HIV antibodies was fitted to the time course of antibody titers of the infected infants. Minimal titers in each infected infant occurred at 5.5, 4.9, and 4.0 months, and doubling times of HIV antibodies from that point ranged from 16.8 to 31.4 days. PMID- 7996004 TI - Autopsy findings in AIDS patients with Mycobacterium avium complex bacteremia. AB - To study the pathogenesis of Mycobacterium avium complex (MAC) bacteremia, the extent of organ involvement was determined in a retrospective cohort of 44 AIDS patients with MAC bacteremia and complete autopsies between 1988 and 1992. Clinical and microbiologic histories were reviewed and lymph nodes, spleen, liver, bone marrow, small intestine, and colon from each autopsy were systematically evaluated for the presence of mycobacteria or foamy histiocytes. Of the patients, 30% had no histologic evidence of MAC. In the remaining 70%, reticuloendothelial and gastrointestinal involvement was most common, but the number and distribution of involved sites was highly variable. The risk of developing detectable histologic involvement was related to the duration of bacteremia. In contrast to the prevailing concept, our data suggest that MAC bacteremia may precede widespread tissue disease. PMID- 7996003 TI - Association between cervical inflammation and cervical shedding of human immunodeficiency virus DNA. AB - A cross-sectional study was conducted among prostitutes in Nairobi, Kenya, to determine the prevalence and correlates of cervical human immunodeficiency virus (HIV) DNA. Ninety-two HIV-seropositive prostitutes were evaluated during 137 clinic visits. Cervical HIV DNA was detected by polymerase chain reaction assay in 36 (39%) women at initial visits and in 40 (44%) women at any visit. There was a significant correlation between cervical HIV and microscopic evidence of cervical inflammation (odds ratio [OR], 7.2; 95% confidence interval [CI], 2.1 24.6). Using multivariate analysis to adjust for possible confounding, the adjusted OR for the association between cervical inflammation and cervical HIV DNA was 8.7 (95% CI, 2.0-37.2). Conditions associated with cervical inflammation are associated with the detection of HIV proviral DNA. Whether such conditions lead to increased infectivity remains to be proven. PMID- 7996005 TI - Characteristics of antibiotic-resistant Escherichia coli O157:H7 in Washington State, 1984-1991. AB - The resistance of Escherichia coli O157:H7 to amoxicillin/clavulanic acid, ampicillin, ceftazidime, ceftriaxone, cefuroxime, cephalothin, chloramphenicol, ciprofloxacin, gentamicin, streptomycin, sulfisoxazole, tetracycline, ticarcillin, tobramycin, and trimethoprim-sulfamethoxazole was examined, and resistant strains were characterized. All 56 isolates collected between 1984 and 1987 were susceptible to all antibiotics tested; 13 (7.4%) of 176 strains isolated between 1989 and 1991 were resistant to streptomycin, sulfisoxazole, and tetracycline. lambda-restriction fragment length polymorphism analysis suggested that the 13 resistant strains belonged to nine different clones. The emerging resistance of E. coli O157:H7 to antibiotics could portend an increased prevalence of this pathogen in food animals that receive antibiotics. Antimicrobial resistance of E. coli O157:H7 could be useful as a rapid epidemiologic marker and as a way to select this pathogen from suspected vehicles of transmission, but this resistance could also complicate therapeutic trials with sulfa-containing antibiotics. PMID- 7996006 TI - Isolates of Escherichia coli O44:H18 of diverse origin are enteroaggregative. AB - One hundred thirteen strains of Escherichia coli O44:H18 isolated in several countries over 25 years were examined for adhesion to tissue culture cells and for hybridization with DNA probes. Fifty-nine strains were from sporadic cases of infection; 54 were from 12 outbreaks. Of the 113 strains, 85 showed aggregative adhesion to HEp-2 cells; 36 were from sporadic cases and 49 were from 9 outbreaks. All adhesive strains hybridized with the probe for enteroaggregative E. coli (EAggEC) and 1 nonadhesive strain was also positive. However, 80 of the 86 EAggEC probe-positive strains also hybridized with the probe for diffusely adherent E. coli (DAEC) derived from the daaC gene of strain F1845. The EAggEC and DAEC probes hybridized to different fragments of a large plasmid in the O44:H18 strains. PMID- 7996007 TI - Experimental evidence for Moraxella-induced penicillin neutralization in pneumococcal pneumonia. AB - Resistance of microorganisms to antimicrobial agents is an increasing problem in the treatment of infectious diseases. In mixed infections, an interesting development can arise when one organism protects another from being killed by an antibiotic. Unfortunately, in the case of respiratory tract infections, experimental evidence of this development is poor. In this study, mice intranasally infected with a lethal number of pneumococci and treated with a curative dose of penicillin or amoxicillin died from pneumococcal pneumonia when they were coinoculated with beta-lactamase-producing Moraxella catarrhalis. beta lactamase-negative M. catarrhalis did not show a similar indirect pathogenic effect. Treatment with a combination of amoxicillin and the beta-lactamase inhibitor clavulanic acid was not affected by beta-lactamase-producing M. catarrhalis. These findings help explain antibiotic failure in respiratory tract infections, even though the causative microorganism is sensitive to the antibiotic in vitro. PMID- 7996008 TI - Epidemiology of chronic Pseudomonas aeruginosa infections in cystic fibrosis. AB - The epidemiology of chronic colonization of airways with Pseudomonas aeruginosa was monitored in 44 patients with cystic fibrosis (CF) by DraI/SpeI macrorestriction analyses of 489 isolates. Sequential P. aeruginosa isolates (144) that had been collected from 32 CF patients over < or = 2.5 years were investigated, and 12 patients were followed for 8 years after onset of colonization. Forty-eight different genotypes were uncovered from 481 typeable isolates. Ten genotypes were found in > 1 unrelated CF patient. The 6 most frequent clones were identified in 58% of isolates. Ten of the 12 patients monitored for 8 years were harboring their initially acquired P. aeruginosa clone at all times, with subtle shifts of fragment patterns indicating subclonal variation. During colonization, the bacteria gradually lost pyocin and phage typing responses, supporting the view that genotypically discordant P. aeruginosa strains develop a common phenotype. PMID- 7996009 TI - Ceftazidime resistance among selected nosocomial gram-negative bacilli in the United States. National Nosocomial Infections Surveillance System. AB - To examine temporal trends in ceftazidime resistance, susceptibility data reported to the National Nosocomial Infections Surveillance system during 1987 1991 were analyzed among nosocomial Enterobacter species, Klebsiella pneumoniae, and Pseudomonas aeruginosa. Linear increases in resistance were observed for Enterobacter species and K. pneumoniae. One hospital experienced a dramatic rise from 1.0% in 1987-1989 to 40% in 1990-1991 (P < .001) in ceftazidime resistance among K. pneumoniae isolates. No increase was observed during this period for P. aeruginosa. Logistic regression analysis confirmed these trends (or the lack thereof) for Enterobacter species and P. aeruginosa; for K. pneumoniae, ceftazidime resistance was found to be increasing among isolates from teaching hospitals and intensive care units. Ceftazidime resistance is an emerging problem that has the potential for dramatic increases. Selective pressures for the development of ceftazidime resistance need to be identified and addressed. PMID- 7996010 TI - Qualitative and semiquantitative polymerase chain reaction to predict Plasmodium falciparum treatment failure. AB - Multidrug-resistant falciparum malaria is increasing in most malaria-endemic areas. Rapid methods for predicting treatment failure would aid management and control of drug-resistant infections. In this study, Plasmodium falciparum DNA clearance was examined by qualitative and semiquantitative polymerase chain reaction (PCR). Thai patients with acute falciparum malaria were prospectively followed by light microscopy and by PCR of P. falciparum DNA eluted from filter paper blood samples. A 206-bp P. falciparum sequence was amplified and detected radiometrically and by high-performance liquid chromatography. Clearance of P. falciparum DNA was significantly delayed in treatment failures compared with that in successfully treated patients (P = .02). Semiquantitative PCR levels did not drop to < 50% of pretreatment levels until day 3 or later in treatment failures compared with day 1 or earlier for successfully treated parasitemia-matched controls (P = .005). These results suggest that qualitative and semiquantitative PCR may be useful as a method for monitoring response to therapy. PMID- 7996011 TI - Failure to detect a Plasmodium vivax-like malaria parasite in globally collected blood samples. AB - Two variants of the circumsporozoite (CS) protein of Plasmodium vivax (VK210 and VK247) have been identified. Recently, a putative third CS variant of P. vivax, referred to as causing P. vivax-like malaria, has been reported from Papua New Guinea. The objective of this study was to confirm and extend findings on the global distribution of the P. vivax-like parasite. Blood samples were obtained from 126 untreated patients with P. vivax infection acquired in Central America, South America, Africa, Southeast Asia, and the Indian subcontinent. The P. vivax CS gene was amplified by polymerase chain reaction and hybridized with probes specific for the VK210, VK247, and P. vivax-like CS variants. All samples were positive for VK210, VK247, or both. No sample was positive for P. vivax-like DNA. Therefore, the existence of a third variant of P. vivax cannot be confirmed in the geographic areas studied. PMID- 7996012 TI - Helicobacter pylori: populations and cohorts. PMID- 7996013 TI - Seoul hantavirus seropositivity among injecting drug users in Baltimore. PMID- 7996014 TI - High levels of interferon-gamma in boutonneuse fever. PMID- 7996015 TI - Monocyte-derived interleukin-8 involved in the recruitment of neutrophils induced by Trichomonas vaginalis infection. PMID- 7996016 TI - [Polymerase chain reaction (PCR) method for the detection of Salmonella by using Chelex resin after enrichment culture]. AB - Salmonella has been implicated as a important pathogen associated with acute gastroenteritis or food borne diseases in humans. Rapid and accurate diagnostic tests for Salmonella are needed by both the food industry and clinical laboratories. A pair of oligonucleotide primers from the phoE gene was used to develop a polymerase chain reaction (PCR) procedure to detect Salmonella spp. When Chelex-extracted DNA from the SBG enrichment culture were used as templates for the PCR amplification (E-Chx), the positive results were obtained with a few cells of Salmonella. This highly specific and sensitive technique gave an efficiency of 1.2 times (73 samples were positive) when tested against conventional culture method (62 samples were positive) using 125 fecal samples stored at 4 degrees C for 1-16 months. Based on the results obtained in this study, it appears that the enrichment-PCR method (E-Chx) using Chelex-extracted DNA described here can be useful to screen a large number of samples such as foods or environmental specimens for contamination of Salmonella. PMID- 7996017 TI - [The improvement on the nursing procedure for pregnant women and newborns and the decrease of Staphylococcus aureus infections in newborns and infants in our hospital]. AB - Knowing the importance of prevention of Staphylococcus aureus infections, especially that of Methicillin-resistant S. aureus (herein after abbreviated as MRSA) in the newborn room, we improved the nursing procedure in the room and examined subsequent changes in the onset condition of the above infection in newborns and infants less than 1-year-old. The infection was detected in 13 cases of stage 1 (stage according to the nursing procedure since the opening of our hospital): 6 cases (all MRSA) had their onset in the room. MRSA was detected in 11 cases, suspecting a hospital cross infection in relation to the period of birth and coagulase type. The infection was detected in 9 cases of stage 2 (stage of prevention of inter-newborn hospital cross infection through environmental purification within the newborn room, through hand and finger disinfection of medical workers, through improved bathing, etc.); 2 cases (1 of MRSA, 1 of Methicillin-sensitive S. aureus [hereinafter abbreviated as MSSA]) had an onset in the room. MRSA was detected in 5 cases, but hospital cross infection was thought difficult to be responsible. The MRSA infection was detected in 4 pregnant cases (0.8%) of stage 3 (stage of effortful prevention of MRSA from carrying into the ward following examination of possible intra-nasal MRSA establishment in pregnant women in addition to similar newborn nursing to stage 2), indicating pregnant women's possible carrying MRSA into the newborn room. S. aureus infection was detected in 9 cases; 2 cases (MSSA) had an onset in the above room.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7996018 TI - [A case of pediatric Chlamydia pneumoniae infection and properties of the isolate]. AB - Chlamydia pneumoniae was isolated from the throat of a 2-year-old girl with upper respiratory illness. The isolate, Shizuoka-37, was stained with C. pneumoniae specific monoclonal antibody (RR402), as well as the genus specific antibody (Cultureset), but not with C. trachomatis specific monoclonal antibody (Micro Trak). C. pneumoniae genome was amplified by polymerase chain reaction in the isolate. Elementary bodies (EB) of the isolate was round shaped by electron micrograph. PMID- 7996019 TI - [Suppression of the Pseudomonas aeruginosa-induced biofilm formation on human epithelial cells by erythromycin]. AB - In the present study, were examined the inhibitory effect of erythromycin on the biofilm formation by a temperature-sensitive mutant (Ts25) of Pseudomonas aeruginosa N-42 on the surface of Ishikawa cells which can produce a mucin-like glycoprotein physicochemically similar to mucoproteins produced in the human airway. Usually, 38-45 microcolonies (biofilms) were formed after 10 days of incubation in cultures of Ishikawa cells and P. aeruginosa Ts25. Erythromcin suppressed the adhesion to Ishikawsa cells of P. aeruginosa and its subsequent biofilm formation at doses as low as 0.2 microgram/ml. Erythromycin also exhibited the suppressive effect on the production of glycoproteins by Ishikawa cells at doses higher than 1 microgram/ml and the production of elastase and exoenxyme A from P. aeruginosa at doses higher than 2 micrograms/ml. These results suggest that erythromycin can inhibit the biofilm formation in culture of human epithelial cells and P. aeruginosa and the in-vivo bacterial biofilm formation may be attributed to host cell-derived factors rather than bacterial products. PMID- 7996020 TI - [Serotype and antibiotic susceptibility of isolates from children with group A streptococcal infection; observation for 10 years]. AB - Six hundred and seventy isolates from children with group A streptococcal infections from 1981 through 1990 were typed serologically and their antibiotic susceptibilities were determined. Productivity of streptococcal pyrogenic exotoxins was also investigated in some isolates. Four hundred and seventy-nine strains were isolated from patients with pharyngitis, 133 from those with scarlet fever, 35 from those with suppurative infection and 23 from those with non suppurative disease. With immediate treatment (antibiotics were started at the same day throat swabs were taken) for 10 days, 5.3% of the patients with pharyngitis including scarlet fever had relapses and 13.4% of those patients had recurrences. Of the episodes of recurrences 15.7% were due to the same M serotype strains. Six patients had two episodes of scarlet fever. M type of isolate was different in the first and the second episode of each patient. Pyrogenic exotoxin type was unprecedented in the second episode of 4 out of 6 patients. M-typable and T-typable rates of isolates were 90.7% and 97.3%, respectively. Coincidence between M and T types was 73.3% (83.0% if including strains with the same and mixed T-type). Prevalent M-serotypes were 12 and 4, but M1, 3, or 28 was the most prevalent type of isolates in certain years. None of the 670 strains was resistant to penicillin G and cephalexin. Resistant rate of isolates to erythromycin and linecomycin was 26.5% in 1981 and 18.4% in 1982. But a marked decrease has noted since 1983 and only one has been resistant since 1986.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7996021 TI - [Positive rates of Neisseria gonorrhoeae and Chlamydia trachomatis on pharynx and rectum of patients with gonococcal or chlamydial genital infections]. AB - In an attempt to know the applicability of non-cultural detection technique for N. gonorrhoeae and C. trachomatis on pharyngeal and rectal swabs, the swabs taken from N. gonorrhoeae- and C. trachomatis-free subjects were tested by Gonozyme, Chlamydiazyme, Ideia Chlamydia, Gen-Probe and Gen Probe Pace 2. As N. gonorrhoeae and C. trachomatis-free subjects, the castrated males older than age 70, with known prostate cancer treated at least for 6 months with anti-androgens who were seronegative for C. trachomatis and had a history of Ofloxacin treatment in the last 3 months and whose pharyngeal and rectal swabs were negative for N. gonorrhoeae, were subjected for study. The false negative rates were for N. gonorrhoeae from the pharynx by Gonozyme 57.7%, by Gen-Probe 0%, by Gen-Probe Pace 2 0%, from rectum by Gonozyme 0%, by Gen-Probe 0% by Gen-Probe Pace 2 0%, for C. trachomatis from pharynx by Chlamydiazyme 93.8%, by Ideia Chlamydia 8.3%, by Gen-Probe 0%, by Gen-Probe Pace 2 0%, from rectum by Chlamydiazyme 94.4%, by Ideia Chlamydia 70.9%, by Gen-Probe 20.0% and by Gen-Probe Pace 2 0%. To investigate the incidence of pharyngeal and rectal infection by N. gonorrhoeae among the patients with gonococcal genital infection, as well as pharyngeal and rectal infection by C. trachomatis among the patients with chlamydial genital infection, pharyngeal and recal swabs obtained from the patients with genital infection by N. gonorrhoeae or C. trachomatis were tested by Gen-Probe Pace 2.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7996022 TI - [Comparison of the prevalence of symptoms, elevated serum antibody, antibody types and complications between two outbreaks of influenza in a ward]. AB - We experienced two outbreaks of influenza in the respiratory ward of our hospital in Feb. 1990 and Feb. 1993. Influenza-like symptoms were recognized in 42 of 67 cases (63%) in 1990, and in 22 of 56 cases (39%) in 1993. In the former outbreak, the prevalence of the serum CF titer for anti-influenza antibody was elevated in 25 of 42 cases (60%) (only the A2 antibody titer in 2 cases, B antibody titer in 4 cases in the latter one). Among asymptomatic inpatients, the serum titer was elevated in 3 of 25 cases (12%) in the former outbreak, but in 1 of 8 cases which the serum CF titer for anti-influenza antibody was measured in the latter one. A respiratory complications secondary to influenza were observed in 6 (2 cases pneumonia, 3 cases lower respiratory tract infection, 1 case asthma attack) of 67 cases during the former period, but only 1 of 56 cases during the latter period. In the two outbreaks of influenza in the respiratory ward we found the same results concerning the occurrence of influenza-like symptoms, an elevation of the serum antibody titer, but a significant difference was noted with regard to the phenotype of the prevalent influenza and the occurrence of complications. PMID- 7996023 TI - [Epidemic of echo 11 virus infection in Gifu Prefecture in 1993]. AB - An epidemic of Echo 11 virus infection occurred in Gifu Prefecture in children. Epidemiological and virological investigations were performed. The results are as follows: 1) Echo 11 viruses were isolated from patients from January to September. Most viruses were isolated in July. 2) Echo 11 viruses were isolated from all areas in Gifu Prefecture, especially from Seino and Hida areas. 3) Cases isolated Echovirus 11 ranged from 0 to 10 years of age, and 83.7% of them were in the 0 to 6 year of age group. 4) Five types of viruses were isolated from 51 of 86 cases (59.3%), and the Echovirus 11 was recovered from 43 cases (84.3%). 5) Echo 11 viruses were isolated from patients of various clinical conditions, but most patients in which isolated Echo 11 virus was isolated had aseptic meningitis, 17 cases (39.5%). Aseptic meningitis occurred in a higher frequency in those above 3 years of age. 6) By the cross neutralizing test between the prototype, isolated strain in 1982 and isolated strains in 1993 of Echovirus 11, a remarkable antigenic variation was not found in isolates in 1982 and 1993. PMID- 7996024 TI - [Serodiagnosis of Legionella pneumonia--data of our laboratory in the recent 3 years]. AB - We had examined antibody titers against Legionella spp. of patients' sera which were mainly sent from other hospitals, performed with the indirect fluorescent antibody (IFA) method. The clinical status of the cases diagnosed as Legionella pneumonia serologically, were also studied. Out of 105 cases with clinically suspected Legionella pneumonia, 15 cases (14.3%) were seropositive. In 9 out of the 15 cases (60.0%) were caused by Legionella pneumophila serogroup 1. Clinical outline of these 15 cases did not contradict those reported in the literature, and erythromycin was effective in many cases. Significant rises (more than four times) of the titer were observed 3 to 4 weeks after onset in most of cases. We would like to emphasize that this should be performed serodiagnosis of Legionella pneumonia. PMID- 7996025 TI - [An evaluation of pathogens in patients with bronchopulmonary infection by transtracheal aspiration: December 1978-March 1993]. AB - We performed transtracheal aspiration (TTA) in 1165 patients, who were suspected to have bronchopulmonary infection, from December 1978 to March 1993. We isolated pathogens from TTA in 806 patients (69.2%). We isolated H. influenzae (62 cases), S. pneumoniae (39 cases) and M. catarrhalis (24 cases) in patients with acute bronchitis, S. pneumoniae (65 cases), alpha-Streptococcus sp. (52 cases), H. influenzae (32 cases) and S. aureus (29 cases) in patients with pneumonia or lung abscess and H. influenzae (174 cases), S. pneumoniae (84 cases), P. aeruginosa (81 cases) and M. catarrhalis (42 cases) in patients with chronic lower respiratory tract infection. Anaerobic bacteria isolated from TTA included Peptostreptococcus sp. (19 cases), Bacteroides sp. (19 cases) and others. Mycoplasma pneumoniae was isolated from TTA in 8 patients with pneumonia without other organisms. Virus isolated from TTA included Rhinovirus (6 cases) and others. These results suggest that various pathogens affect the pathogenesis of bronchopulmonary infection. Therefore, we must diagnose the bronchopulmonary infection by the correct methods such as TTA. PMID- 7996026 TI - [Evaluation of gelatin particle agglutination method for detection of Treponema pallidum antibody]. AB - Treponema pallidum hemagglutination (HA) is one of the most frequently used methods for the detection of Treponema pallidum (T. pallidum) antibodies. Recently, an innovative agglutination method using artificial carriers was newly developed, and is now available as a routine method. In order to compare the newly developed particle agglutination (PA) method (FUJIREBIO INC.) with the conventional HA method, T. pallidum antibody titers of numerous sera were measured by respective methods. In the stability study, reconstituted reagent was stable for at least three weeks. Sample inactivation (56 degrees C/30 min) demonstrated no effect on the test results. Among 800 sera, 132 (16.6%) positives (+), 633 (79.1%) negatives (-) and (4.3%) indeterminates (+) were obtained by HA method. Meanwhile, 144 (18.0%) positives (+), 627 (78.4%) negatives (-) and 29 (3.6%) indeterminates (+) were obtained by PA method. The correlation between PA and HA method was 97.8%, and the antibody titers obtained by PA method showed good correlation with HA method. Those samples which showed discrepancy between PA and HA method in the above study were further examined with fluorescent treponemal antibody-absorption (FTA-ABS) method. The results obtained from FTA ABS method were almost consistent with those obtained from PA method. For respective syphilis patients in stage I and II, antibody titer was monitored by HA, PA and RPR method. The results indicated that changes in antibody titer obtained from PA method was approximately the same as the titer changes obtained from RPR method. Namely, PA method detected the presence of IgM earlier than HA method.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7996027 TI - [Evaluation of direct immunoperoxidase technique using F(ab')2 fractions of anti cytomegalovirus human monoclonal antibody for enumeration of cytomegalovirus antigen-positive leukocytes]. AB - Direct immunoperoxidase technique using human monoclonal antibody (C7) against a p65 antigen of cytomegalovirus (CMV) has been utilized to detect CMV antigen positive leukocytes in the peripheral blood (CMV antigenemia). This technique was evaluated for enumeration of CMV antigen-positive leukocytes. The parameters included stability of the reagents, reproducibility of the results and quantitativity of the detection. The horseradish peroxidase (HRR)-labeled F(ab')2 fractions of C7 antibody were found to be superior to the equivalent Fab' fractions, because the former was much more stable than the latter. Enumeration of the CMV antigen-positive leukocytes were very reproducible and quantitative. The detection limit was one CMV antigen-positive cell per 50,000 leukocytes. Thus, this technique is reliable and practical to detect the CMV antigenemia, and it will contribute to early diagnosis of CMV diseases and initiation of antiviral therapy. PMID- 7996028 TI - [Effect of CO2 on mucoid Pseudomonas aeruginosa]. PMID- 7996029 TI - [Bactericidal effects of gentian violet (Gv) and acrinol (Ac) against methicillin resistant Staphylococcus aureus (MRSA) and gram-negative bacteria isolated from clinical materials]. PMID- 7996030 TI - ECG of the month. Twin spikes. Pacemaker rhythm. PMID- 7996031 TI - Sudden idiopathic sensorineural hearing loss. AB - Sudden loss of hearing can be a very frightening experience for the patient and frustrating for the physician. The etiology is often difficult to identify and several theories have been proposed to explain sudden "idiopathic" sensorineural hearing loss. These theories include the viral theory, the vascular theory, and the membrane rupture theory. As the etiology is uncertain, many treatment modalities have been proposed. Steroids are the only effective medical treatment to date. Surgery may be employed when evidence of perilymphatic fistula exists. Controlled studies are needed to determine the effectiveness of proposed treatment modalities. PMID- 7996032 TI - Futility. PMID- 7996033 TI - Long-term survival in small cell lung cancer with superior vena caval obstruction. AB - Two patients were diagnosed with small cell lung cancer and superior vena caval obstruction. Successful palliation of symptoms with significant reduction in size of the intrathoracic lesion was achieved with radiation therapy and chemotherapy. Treatment resulted in complete remission with long-term (more than 3 years) survival. These two cases affirm the fact that, despite the generally recognized poor prognosis of small cell lung cancer associated with this syndrome, aggressive therapy can sometimes provide rewarding results. PMID- 7996034 TI - Emergency medical services development in the state of Louisiana. AB - Management of Emergency Medical Services has been sadly forgotten over the years in the state of Louisiana. A new task force which was formed over a year ago is now beginning to formulate a direction for the future of EMS in this state. At its last Annual Meeting, the LSMS adopted a resolution to support the work and decisions made by that task force. The EMS task force pulled together firefighters, emergency medical technicians, ambulance employees, and a group of physicians representing the specialities of trauma, emergency medicine, and pediatrics. Subcommittees were formed to address legislation, licensure, education, medical control, and pediatric issues. Definitive direction for the Bureau of EMS has been formulated with the aid of the task force and its various subcommittees. The LSMS as a whole supports this initiative; however, for it to succeed, the entire membership must understand the importance of EMS to everyone in the state. Good out-of-hospital care will determine whether a person gets early thrombolytic care, whether early defibrillation is available at their sides, and whether their child is treated with "pediatric appropriate" approaches to medical care. The life saved could be important to any one of us. The purpose of this article is to acquaint the membership with what EMS is, what the condition of EMS in Louisiana is, and what the progress of the EMS task force has been. PMID- 7996035 TI - Pulmonary nodular amyloidosis in a patient with Sjogren's syndrome diagnosed by transthoracic biopsy. AB - A variety of pulmonary diseases may accompany Sjogren's syndrome. We report a rare case of pulmonary nodular amyloidosis in a woman with Sjogren's syndrome that was diagnosed by fluoroscopic transthoracic needle biopsy. PMID- 7996036 TI - Informed consent update for Louisiana. Reducing the risk of malpractice suits. AB - The Louisiana Medical Disclosure Panel is a group of physicians, attorneys, and an oral surgeon whose duty is to supply a format that should be used to provide adequate information for patients about to undergo medical or surgical therapy. The Panel also provides the list of risks the physician should outline to the patient in order to obtain informed consent before the procedure. Physicians who use the form and the list of risks the Panel developed afford themselves the best protection from malpractice litigation currently available in Louisiana. PMID- 7996037 TI - Is this a great profession, or what? PMID- 7996038 TI - Meconium staining: is it related to maternal smoking? AB - The present study was undertaken to find if pregnant women's smoking habits were related to the presence of meconium in the amniotic fluid. The medical records of 58 women admitted to the OB service between January 1, 1992, and December 31, 1992, were reviewed. Data from the records was analyzed. Findings indicated that smoking was not related to the presence of meconium in the amniotic fluid. Some women who did not smoke had meconium stained amniotic fluid. Some women who smoked had no meconium staining. A relationship between meconium staining and maternal smoking habits was not supported. PMID- 7996039 TI - The use of exogenous surfactant replacement therapy in newborns with non respiratory distress syndrome conditions. PMID- 7996040 TI - Congenital cytomegalovirus disease in the Louisville area: a significant public health problem. AB - Using a passive surveillance system, 15 cases of symptomatic congenital cytomegalovirus (CMV) infection were identified in the Louisville area over approximately 3 years. When compared to mothers delivering healthy infants in Jefferson County, mothers of infants with congenital CMV were younger, more often nonwhite, and from lower socioeconomic status. Affected infants had a lower mean gestational age and birth weight, and most demonstrated classic features of congenital CMV infection such as jaundice, petechiae, hepatosplenomegaly, intrauterine growth retardation, and microcephaly. The overall infant mortality rate was 33%. Maternal and infant characteristics were similar to those of 167 cases in a national database and 106 cases reported from Birmingham, Alabama. The estimated minimal incidence of symptomatic congenital CMV disease in this area was 1.16/10,000 live births for white and 6.06/10,000 for nonwhites, establishing this as a significant public health problem in this part of Kentucky. PMID- 7996042 TI - Now count your men, Hitler. PMID- 7996041 TI - Robert R. Goodin, MD. KMA President 1994-95. PMID- 7996043 TI - Neutrophils, host defense, and inflammation: a double-edged sword. AB - Neutrophils play important roles in host defense against all classes of infectious agents but, paradoxically, they are also involved in the pathology of various inflammatory conditions. Their microbicidal armory consists of oxidative and nonoxidative processes that are activated simultaneously upon phagocytosis. Although destruction of infectious agents occurs intracellularly, release of cytotoxic molecules into the extracellular milieu can damage body tissues. Neutrophils are heterogeneous. Subpopulations exist in various stages from dormant to primed to fully activated. The activities of neutrophils are regulated locally in microenvironments and systemically by a plethora of mediators including cytokines, "classical" neuroendocrine hormones, and bioactive lipids. The net response depends on a complex balance of stimulatory and inhibitory pathways that are regulated by these mediators. Although some effector and regulatory pathways are vital, considerable redundancy is also evident. Identification of the essential mediators and the unraveling of any interactions may be the keys to understanding the neutrophil paradox and developing therapeutic strategies that optimize microbial killing and minimize host tissue damage. Finally, reports that neutrophils can act as drug delivery vectors and that their function is influenced by stress and other lifestyle factors suggest that new homeostatic functions for these cells, outside their traditional roles in host defense and inflammation, remain to be identified: some are speculated on here. PMID- 7996044 TI - Summary of the fifth conference on the molecular mechanisms and physiological activities of cytokines. PMID- 7996045 TI - Quantitative recovery of pulmonary intravascular macrophages from sheep lungs. AB - Pulmonary intravascular macrophages (PIMs) adhere to the endothelium of lung capillaries and sequester circulating particles and pathogens from the blood. Iron oxide (gamma Fe2O3) 5 mg/kg, administered intravenously, specifically labeled PIMs in situ within the living sheep. Attempts to isolate gamma Fe2O3 labeled PIMs using vascular perfusion (VP) procedures yielded few cells. To improve recovery of PIMs, a proteolytic lung digestion (PLD) procedure was developed. Following PLD, gamma Fe2O3-containing PIMs were recovered by magnets and the amount of gamma Fe2O3 present measured by fluxgate magnetometry. Proteolytic lung digestion recovered 34% of the total gamma Fe2O3 in lung samples and yielded 2 x 10(5) PIMs/g lung with 95% viability. In contrast, VP recovered only 3% of the total gamma Fe2O3 in the lung; furthermore, less than 2% of the recovered gamma Fe2O3 was cell associated. Proteolytic lung digestion followed by magnetic separation is an effective way to recover viable sheep PIMs for in vitro study. PMID- 7996046 TI - Role for oxygen radicals in self-sustained HIV-1 replication in monocyte-derived macrophages: enhanced HIV-1 replication by N-acetyl-L-cysteine. AB - N-acetyl-L-cysteine (NAC) has been proposed as a therapeutic agent for AIDS patients because it reduces human immunodeficiency virus type 1 (HIV-1) replication in stimulated T cells. However, NAC and glutathione enhanced acute HIV-1 replication in monocyte-derived macrophages. Buthionine sulfoximine did not affect NAC-mediated enhanced HIV-1 replication, indicating that the NAC-mediated effects are glutathione-independent. Superoxide dismutase and the hydroxyl radical scavengers dimethylthiourea and thiourea, but not urea, inhibited acute HIV-1 replication in macrophages. NAC reduced ferricytochrome c and increased dose-dependently Fe(III)-citrate and Fe(III)-EDTA-catalyzed hydroxyl radical formation in a system using glucose and glucose oxidase. Dimethylthiourea and thiourea, but not urea and superoxide dismutase, dose-dependently inhibited NAC mediated enhancement of HIV-1 replication. These data suggest that oxygen radicals play an important role in self-sustained HIV-1 replication in macrophages and that oxygen radical scavengers other than NAC should be considered as therapeutic agents for AIDS patients. PMID- 7996047 TI - Lipopolysaccharide and splenic tumoricidal macrophage activation. AB - Splenic macrophage tumoricidal activity was examined and a splenic macrophage tumoricidal assay was established. Initially, mixtures of lipopolysaccharide (LPS) and spleen single cell suspensions (SSCS) were cultured for 1-4 days. Adherent macrophages, washed free of nonadherent cells and LPS, were then examined and were found to lack tumoricidal activity in a standard 18-h 51Cr release assay. However, tumoricidal activity was generated if LPS was added to the SSCS cultures at later time points during the 4-day incubation period; maximal activity was seen when LPS was added on day 3. In parallel, significant changes in macrophage autofluorescence and morphology, but not phenotype, were observed. Next, SSCS were cultured for 1-4 days without stimulating agents. Adherent macrophages were then washed free of nonadherent cells and LPS was added. Significant tumoricidal activity developed in time- and LPS concentration dependent fashions. The presence of nonadherent spleen cells in physical contact with the macrophages during the SSCS culture was essential for the macrophages in the resultant monolayer to be responsive to LPS. Activated splenic macrophage mediated lysis of tumor cells was shown to depend on the contact between the two cells. PMID- 7996048 TI - Activation of arachidonic acid metabolism in mouse macrophages by bacterial amphiphiles. AB - The relative activities of lipoteichoic acid (LTA) from four Gram-positive bacteria were compared to different lipopolysaccharide (LPS) preparations for activation of arachidonic acid metabolism in mouse peritoneal macrophages. Total eicosanoid was determined in cultures labeled with [3H]-arachidonic acid. Prostaglandin E2 (PGE2) and leukotriene C4 (LTC4) were determined by EIA analysis. The relative potencies of the different preparations were: smooth LPS from Salmonella abortus > or = Re-LPS from Salmonella minnesota (R-595) > or = LTA from Streptococcus pyogenes approximately Streptococcus faecalis approximately Staphylococcus aureus > or = monophosphoryl lipid A derived from the Re-LPS >> LTA from Bacillus subtilis. Activation of eicosanoid release was inhibited by staurosporin for all of the amphiphiles tested. Treatment of the macrophage cultures with LTA from S. pyogenes, S. faecalis, and S. aureus, either in the presence or absence of indomethacin, desensitized the cells to eicosanoid release on subsequent challenge with LPS. The desensitized cells remained responsive to the phorbol ester phorbol myristate acetate. LPS from Gram-negative bacteria has immunostimulatory and endotoxic activities which result, in part, from the release of eicosanoids and other mediators from activated macrophages. The similarities in the patterns of cell activation by LPS and LTA suggest that lipoteichoic acids might contribute to the pathogenicities of Gram-positive bacteria. PMID- 7996049 TI - Differential effects of temperature on macrophages of ectothermic vertebrates. AB - The role of macrophages in vertebrate defense reactions is especially important at low temperatures, which commonly affect representatives of ectothermic species. The aim of this work was to compare the effects of in vivo thermal acclimation and in vitro assay temperatures on peritoneal macrophages (PMs) from fish (carp and goldfish) and amphibians (salamanders and toads). The substratum adherence of PMs was undisturbed over the wide range of temperatures experienced by animals in nature. Dehydrogenases and endocytosis were sensitive to temperature fluctuations in a species-specific manner, more or less dependent on the previous thermal history of animals. The MTT reduction, inhibited by low assay temperatures, was slightly improved in PMs from cold-acclimated amphibians but not fishes. Endocytosis by the amphibian PMs, very efficient over the wide range of assay temperatures, was additionally improved by previous in vivo cold exposure. Contrasting effects of thermal acclimation were most evident in the case of endocytic properties of fish PMs; endocytosis by PMs from cold-acclimated fishes was extraordinarily efficient at a temperature just above zero, which almost completely inhibited cells from fishes adapted to warmth. PMID- 7996050 TI - Human microglial cells have phenotypic and functional characteristics in common with both macrophages and dendritic antigen-presenting cells. AB - Resting microglia comprise up to 13% of the cells in human central nervous system (CNS) white matter. Their large number and dendritic morphology make them ideally suited to survey the CNS for noxious stimuli. Upon activation microglia gradually lose dendritic processes and transform into typical phagocytic macrophages. Microglia have been implicated as the main antigen presenting cell within the CNS, and appear to be of central importance as effectors and regulators of demyelination. To further characterize the capacity for immune reactivity within the human CNS, we have studied several characteristics of microglia, both in situ and in vitro. We find that human microglia have ultrastructural, phenotypic (CD11c, CD68, acid phosphatase), and functional (FcR and CR mediated phagocytosis) properties typical for cells of the monocyte lineage. Our data indicate that microglia also have properties in common with dendritic antigen presenting cells. Electron microscopy studies show extended dendritic cell processes on cultured microglia, and microglia are, like dendritic cells, negative for the monocyte markers nonspecific esterase, endogenous peroxidase, CD14, and RFD7. Microglia constitutively express HLA-DR in situ, and express the dendritic cell marker RFD1 upon activation. Coculturing of microglia with CD4+ T cells results in clustering of T cells around microglia and initiation of a mixed lymphocyte reaction, both distinguishing features of dendritic cells. These functional properties of microglia may be of importance for the maintenance of an immunologic response in the CNS, an organ where dendritic cells, in contrast to other organs, have not previously been identified. PMID- 7996051 TI - The role of IL-4, IL-10, and TNF-alpha in the immune suppression induced by ultraviolet radiation. AB - Cytokines produced by keratinocytes play an essential role in the induction of immune suppression following ultraviolet (UV) exposure. Using antibodies specific for either interleukin-10 (IL-10) or tumor necrosis factor alpha (TNF-alpha), we present evidence indicating that IL-10 suppresses delayed-type hypersensitivity (DTH) but not contact hypersensitivity (CHS), whereas TNF-alpha suppresses CHS but not DTH following UV exposure. UV exposure also activates antigen-specific suppressor T cells. To determine whether the antigen-specific CD4+ T cells that transfer suppression in this system mediate their suppressive effect by releasing IL-4 or IL-10, we transferred UV Ts into normal mice that were then injected with either anti-IL-4 or anti-IL-10 antibody. Both anti-IL-4 and anti-IL-10 blocked the ability of UV Ts cells to suppress DTH in the recipient animals. When UV Ts that suppress CHS were transferred into normal recipients, however, neither antibody was able to block the UV Ts activity. These findings suggest that UV Ts suppress DTH by secreting IL-4 and IL-10 and appear to act like Th2 cells. Because anti-IL-4 and anti-IL-10 did not block the activity of the UV Ts that regulate contact hypersensitivity, their effects appear to be mediated by a different mechanism. PMID- 7996052 TI - Modulation of the chemotactic responsiveness of guinea pig neutrophils to hrIL-8 and fMLP. AB - Neutrophils elicited in the peritoneal cavity of guinea pigs were purified on Percoll gradients and their chemotactic response to hrIL-8 and fMLP measured in vitro. hrIL-8 and fMLP were effective chemoattractants with optimal concentrations of 6 x 10(-9) and 1 x 10(-7) M, respectively. Scatchard analysis revealed approximately 205,000 IL-8 receptors/cell and 34,000 fMLP receptors/cell with KD values of 4.1 x 10(-9) and 3.3 x 10(-8) M, respectively. At suboptimal concentrations of chemoattractants the response was inhibited by dibutyryl cyclic AMP, histamine, and adenosine in the presence of a phosphodiesterase inhibitor. IL-8 and fMLP induced an increase in cellular cyclic AMP and the response to optimal concentrations of chemoattractants was inhibited by Calphostin C and Ro 31-8220, inhibitors of protein kinase C (PKC). Our results indicate that the chemoattractants activate the same PKC-dependent pathway that is down-regulated by cyclic AMP-dependent mechanisms. PMID- 7996054 TI - Glycosylphosphatidylinositol-anchored NAD glycohydrolase is released from peritoneal macrophages activated by interferon-gamma and lipopolysaccharide. AB - We have previously shown that an ectoenzyme, NAD glycohydrolase (NADase) could be solubilized by treatment with bacterial phosphatidylinositol phospholipase C (PIPLC). However, it is unknown whether endogenous PIPLC can cleave this ectoenzyme. In this study, we used mouse peritoneal exudate macrophages which have been known to have relatively high activity of NADase. The results show that release of ecto-NADase was markedly increased when mouse peritoneal macrophages were costimulated with interferon-gamma (IFN-gamma) and bacterial lipopolysaccharide (LPS), compared to unstimulated cells. This increase was preceded by markedly enhanced activity of endogenous glycosylphosphatidylinositol phospholipase C (GPIPLC). The cross-reacting determinant (CRD) of the glycosylphosphatidylinositol anchor in released NADase from activated macrophages was detected by immunoblotting with anti-CRD antibody. Taken together, ecto NADase is release from peritoneal exudate macrophages during IFN-gamma/LPS induced activation and endogenous GPIPLC is involved in the NADase release from the activated macrophages. PMID- 7996053 TI - Identification and characterization of a bovine lipopolysaccharide-binding protein. AB - Endogenous regulatory mechanisms exist in mammals that enable a rapid response to lipopolysaccharide (LPS, endotoxin) stemming from gram-negative bacterial infections. Serum proteins and cell surface receptors exist that bind LPS, and this interaction may either aid in nonpathogenic removal of LPS from the body or potentiate the effects of LPS. We have used a photoreactive, thiol-cleavable, radiolabeled derivative of E. coli 0111:B4 LPS [LPS-(p-azidosalicylamido)-1,3' dithiopropionamide; 125I-ASD-LPS], to identify the presence of LPS-binding proteins (LBPs) in bovine serum. Ion exchange chromatography was used to fractionate bovine serum, and eluted protein was subsequently photoaffinity labeled using 125I-ASD-LPS. LBPs were identified by autoradiography of sodium dodecyl sulfate-polyacrylamide gels. Several LBPs including three with apparent molecular masses of 65, 60, and 50 kDa were variably present within the chromatography pools. A 22-residue NH2-terminal amino acid sequence of the 60-kDa protein showed 77% homology with human LBP and 68% with rabbit LBP within this region. Further purification utilizing high-performance liquid chromatography yielded a protein fraction that contained the 60-kDa protein and was distinctly more active than whole bovine serum in LPS-dependent macrophage activation assays (up to 1600-fold on a weight/volume basis). The LPS-mediated macrophage activation in concert with chromatographically purified serum protein in tissue factor assays was inhibitable using anti-CD14 monoclonal antibodies. The results indicate that an LPS-binding protein exists in samples of pooled bovine serum and that this protein has features in common with human and rabbit LBP. PMID- 7996055 TI - Enhancement of murine serum amyloid A3 mRNA expression by glucocorticoids and its regulation by cytokines. AB - Macrophages are regulated by hormones, cytokines, and other substances. We examined the effects of glucocorticoids (GC) on serum amyloid A (SAA) mRNA expression using an antisense SAA3 probe, and found that dexamethasone (DEX) and triamcinolone (TC) increased SAA3 mRNA expression by macrophage cell lines in a time- and concentration-dependent manner. Both an RNA polymerase II antagonist, alpha-amanitin, and a specific GC antagonist, RU38486, inhibited the enhancement of SAA3 mRNA expression by DEX. These results show that GC lead to enhanced SAA3 mRNA transcription. Nuclear run-on experiments supported these results. Enhanced expression of SAA3 mRNA by DEX was accompanied by production of SAA3 protein. Interferon-gamma (IFN-gamma) alone showed any effect on SAA3 mRNA expression. Enhanced SAA3 expression by DEX was inhibited by treatment with IFN-gamma in a dose-dependent manner. Either transforming growth factor (TGF)-beta 1 or interleukin (IL)-4 alone showed no effect on SAA3 mRNA expression, but suppressed DEX-induced SAA3 expression. The timing of the effects of IFN-gamma and TGF-beta 1 on DEX-induced SAA3 expression differed: IFN-gamma showed its effect between 30 h before and 18 h after DEX administration, whereas TGF-beta 1 showed an effect when administered concomitantly with DEX and in the late stages after DEX administration. IL-4 mildly suppressed DEX-induced SAA3 expression when given 12 h before and after DEX administration. PMID- 7996056 TI - Identification of a proline-arginine-rich antibacterial peptide from neutrophils that is analogous to PR-39, an antibacterial peptide from the small intestine. AB - Neutrophil nonoxidative defense mechanisms include several low molecular weight antimicrobial peptides. We have isolated a proline-arginine-rich antibacterial peptide from porcine neutrophils. This cationic, low molecular weight peptide has a very high degree of identity (97%) to a bactericidal peptide, PR-39, that has been found in the porcine small intestine. Isolation of the same antimicrobial peptide from both neutrophils and cells of the small intestine in the same species is unique and suggests an important role for this protein in innate immune defenses. PMID- 7996057 TI - Surface IgM-stimulated proliferation, inositol phospholipid hydrolysis, Ca2+ flux, and tyrosine phosphorylation are not altered in B cells from p59fyn-1- mice. AB - The surface immunoglobulin M (sIgM)-associated src family protein tyrosine kinases (PTKs) p55blk, p59fyn, and p53/56lyn become activated in B cells within seconds following sIgM cross-linking. Studies using protein tyrosine kinase (PTK) inhibitors have demonstrated that PTK activity is crucial for downstream events such as calcium flux, inositol phospholipid hydrolysis, and cell cycle entry. The roles that the individual src family PTKs play in sIgM signaling are largely unknown, however. In order to determine whether p59fyn plays a distinct role in sIgM signal transduction, the signaling capabilities of B cells isolated from fyn "knockout" mice were evaluated. We observed that in the absence of p59fyn, there was no demonstrable compromise of the sIgM-coupled signaling events measured (tyrosine phosphorylation, inositol phospholipid hydrolysis, and Ca2+ flux). We propose that either p59fyn is not involved in coupling sIgM to these specific signaling pathways or that other PTKs are able to compensate for the absence of p59fyn, indicating redundancy in the sIgM signaling pathways. PMID- 7996059 TI - Microaerophilic streptococci as a significant pathogen: a twelve-year review. AB - One hundred twenty three microaerophilic streptococci (MS) were isolated from 4,603 specimens submitted for the identification of anaerobic bacteria over the course of 12 years. The MS included 16 Streptococcus constellatus, 43 Streptococcus intermedius and 21 Gemella morbillorum. A total of 81 MS isolates (66%) identified from 75 patients were considered to cause infection. Predisposing or underlying conditions were noted in 48 (64%) patients. The most common conditions were previous surgery (15 instances), trauma (10), diabetes (9), immunodeficiency (6), malignancy, and prosthetic device (5 each). MS were the only bacterial isolates in 23 instances. Mixed infection was encountered in 52 (69%) patients, where the number of isolates varied between two and five (average 2.7). The organisms most commonly isolated with MS were anaerobic cocci, Bacteroides sp. and Enterobacteriaceae; their recovery varied at different sites. Significant infections caused by MS were associated with abscess (29 instances), sinuses (7), obstetrical and gynecological (OBG), chest and wounds (6 each), abdominal (5), and biliary infection (4). Antimicrobial therapy as administered to 71 patients; for 43 patients, in conjunction with surgical drainage or correction. Surgical drainage alone was performed in three patients. Four patients (5%) died. These data illustrate that MS can occasionally be associated with serious infection. PMID- 7996058 TI - Influence of age on the production of Fos and Jun by influenza virus-exposed T cells. AB - This study investigated age-related T cell responses after in vitro exposure to influenza A virus. Mononuclear leukocytes from young or elderly persons were sham exposed or exposed to influenza virus for 1, 24, and 72 h. Immunofluorescent staining and flow cytometric analysis were then used to detect T cells producing the transcriptional regulating proteins Fos and Jun. Fewer virus-exposed cells from elderly donors stained for Fos and Jun at each data point compared with cells from young donors. Flow cytometric analysis also showed that at 72 h of virus exposure fewer T cells from the elderly produced interferon-gamma (IFN gamma), suggesting a link between the magnitude of the Fos and Jun and IFN-gamma responses. Thus, failure of virus-exposed T cells to produce Fos and Jun could contribute to the increase in illness due to influenza virus in the elderly. PMID- 7996060 TI - Potentiation of thrombolytic therapy by enzyme combinations and with aspirin or pentoxifylline. AB - Radioactively labeled human fibrin clots were placed into veins of Macaca arctoides monkeys. Thrombolysis was recorded by the disappearance of radioactivity and by angiography. Streptokinase (SK) and urokinase (UK) induced thrombolysis was potentiated by low dose aspirin (ASA) and pentoxifylline (PE). Studies on the mechanisms of action revealed that PE inhibits platelet aggregation, releases tissue plasminogen activator (t-PA) from the endothelium, increases red cell deformability and inhibits white cell adhesion. Thrombolysis by pro-urokinase (pro-UK) was potentiated by low dose SK probably because of streptokinase-plasmin activation of pro-UK to UK. Platelet aggregation inhibitory effects, disaggregation of platelet aggregate inducing effects, and the t-PA releasing activity of PE was demonstrated in patients with obstructive cardiovascular disease. Pharmacodynamic studies suggested that PE metabolites one and five are most effective from this point of view. These metabolites are currently studied in combination with thrombolytic enzymes. PMID- 7996061 TI - A phase I study of curdlan sulfate--an HIV inhibitor. Tolerance, pharmacokinetics and effects on coagulation and on CD4 lymphocytes. AB - Curdlan sulfate (CRDS) is a semi-synthetic sulfated polysaccharide which has anti HIV activity in vitro, and inhibits attachment of the virus to T-cells. After two weeks of exposure of virus and cells to CRDS, there is complete inhibition of virus replication. CRDS is also active against cytomegalovirus. The favorable toxicological profile of CRDS in animals suggested clinical trials. In this study, doses of 0.014, 0.14, 0.42, 1.42, 2.84 and 4.26 mg/Kg (hereinafter referred to as 1, 10, 30, 100, 200 and 300 mg/body, respectively, for convenience) were administered to three HIV-positive patients at each dose level for four hours intravenously. Activated partial thromboplastin times (APTT) were measured hourly. Unexpectedly, single doses of CRDS produced marked, dose related, increases in CD4 lymphocytes in HIV-infected patients. There were no clinical side effects seen at any dose tested. All laboratory parameters were normal except for prolongation of APTT in the 200 and 300 mg dose group. Two patients in the 300 mg dose group had a doubling of the APTT during the four hour infusion, which was the termination point of the trial according to the protocol. The half-life of CRDS was estimated to be 2 to 3 hours from the APTT data and from the blood level assays (not shown). CRDS was well tolerated in the study with the APTT levels being a convenient monitoring basis for dosing. Marked increases in CD4 levels were seen at higher doses, which, if confirmed and extended, may have therapeutic implications. CRDS is considered safe for multiple dosing with monitoring of APTT. PMID- 7996062 TI - Plasma neurotransmitters and cortisol in chronic illness: role of stress. AB - We routinely measured plasma neurotransmitters and hormone levels in order to investigate the role of stress on many types of diseases. In this study, we present results obtained from patients with severe chronic diseases. The study sample consisted of 88 patients (asthmatics, ulcerative colitis, Crohn's disease, chronic active hepatitis, chronic relapsing hepatitis, multiple sclerosis, trigeminal neuralgia, systemic lupus erithematous, and rheumatoid arthritis), and their respective controls. Noradrenaline (NA), adrenaline (Ad), dopamine (DA), platelet-serotonin (pS), free-serotonin (fS), growth hormone (GH) and cortisol (CRT) were determined during both exacerbation and improvement periods. A profile compatible with uncoping stress disorder (raised NA-Ad-DA + fS + CRT as well as low pS and NA/Ad ratio) was found during exacerbation periods when compared with improvement, as seen in controls. However, during improvement periods the neurochemical profile remained significantly different from that of normal controls. The neurochemical plus hormonal plasma profiles registered in chronic illness, both during exacerbation and improvement periods, strongly suggest that an uncoping stress mechanism underlies diseases of these patients. PMID- 7996063 TI - Infusional cisplatin and etoposide in the treatment of stage III-B and IV non small cell lung cancer: a well tolerated regimen. AB - Twenty-eight evaluable patients were treated with an infusion of cisplatin and etoposide for advanced non-small cell lung cancer. A response was demonstrated in 43%, although only two patients had documented partial responses. The regimen was surprisingly low in toxicity, both acute and chronic, and is suitable for palliation of patients who are elderly or suffer from chronic illnesses which preclude more agressive therapy. PMID- 7996064 TI - In vitro micro-autoradiography of atrial natriuretic peptide in biopsy specimens from patients with renal diseases. AB - We investigated the localization and density of atrial natriuretic peptide (ANP) receptors in human renal biopsy specimens by using in vitro micro-autoradiography (ARG) of [125I]-alpha-human (1-28) ANP. In a preliminary study, we measured the effect of storing tissue samples on ANP binding, using in vitro micro-ARG of Wistar rat kidney under optimal conditions. Duration of the preservation period did not affect ANP binding to renal tissue until samples had been stored at -30 degrees C for two years. A total of 11 human renal tissues were used to assay binding of ANP-ARG, including normal tissue obtained after nephrectomy because of renal cancer. ANP binding occurred predominantly within the glomerulus and, to a lesser extent, in the tubular region both in rat kidney sections and in human renal biopsy specimens. The density of ANP binding, calculated by counting grains in fixed areas, was compared with normal and pathological tissues. The density of grains tended to decrease in patients with renal dysfunction and hypertension except for one case of IgA nephropathy with normal renal function and blood pressure. The density of grains increased in a patient with nephrogenic diabetes insipidus. In the present study, we have established a method that uses in vitro micro-ARG for assessing ANP binding in human biopsy specimens. PMID- 7996065 TI - Hyperglycemia, ketoacidosis and other complications of L-asparaginase in children with acute lymphoblastic leukemia. AB - We show Escherichia coli derived L-asparaginase complications observed in 14 of 136 acute lymphoblastic leukemia patients during remission induction therapy according to St. Jude Children's Hospital Total XI Protocol. We observed hyperglycemia in six patients; two of them had accompanying ketoacidosis. One of the cases with ketoacidosis had peritonitis and pancreatitis. Central nervous system symptoms such as convulsions and depression with personality changes (in one case) were observed in four of these six hyperglycemic patients. Intracranial bleeding and ischemic infarction were shown in cranial computed tomographies in two cases. Hypersensitivity reactions were observed in seven patients. Patients were randomly assigned into two groups and treated with conventional dose steroids or high dose methylprednisolone. Although the frequency of hypersensitivity reactions were lower in the high dose methylprednisolone group, one patient in this group had an anaphylactic reaction. These findings once again high-light L-asparaginase complications which are not dose dependent and can be life threatening. PMID- 7996066 TI - Chronic autoimmune hemolytic anemia in children: a report of four patients. AB - Four children, ages seven to ten years, with direct antiglobulin test (DAT) positive chronic hemolytic anemia are presented. The patients were followed for 3 to 10 years. Autoantibody against red cell antigens was nonspecific IgG type in all of the patients. In one of the four patients, anemia was associated with splenomegaly and jaundice. In this patient, the third component of the complement was also detected on the red cell surface. In one patient, serum IgA deficiency and frequent pulmonary infections were associated with the disease. This patient developed rheumatoid arthritis five years after diagnosis of hemolytic anemia. The third patient initially had thrombocytopenia subsequently developed DAT positive hemolytic anemia, vitiligo and alopecia without any evidence of serologic changes suggestive of collagen vascular disorders. In these three patients, partial response was obtained with steroid therapy. The fourth patient developed DAT-positive hemolytic anemia twice during the five year follow-up period. Anemia resolved completely with steroid therapy in two months during the first episode, and in five months in the second. Generalized and peripheral lymphadenopathies which developed at the time of the second hemolytic anemia episode have persisted for the last three years. Administration of cyclosporine in two of the four patients did not result in any amelioration of the symptoms. PMID- 7996067 TI - TMJ: a well-tolerated high-dose regimen for the adjuvant chemotherapy of high risk breast cancer. AB - Following local treatment and doxorubicin-containing standard chemotherapy, 42 patients with surgical Stage II or IIIA breast cancer containing ten or more involved axillary nodes and 13 patients with Stage IIIB disease were treated with high-dose chemotherapy (TMJ) consisting of thiotepa (750 mg/m2), mitoxantrone (40 mg/m2), and carboplatin (1000 mg/m2), with autologous bone marrow (ABM) and peripheral stem cell (PSC) transplant, followed by irradiation and/or hormone therapy. Sargramostim (GM-CSF) support was given to most patients. The median time to transfusion independence was two weeks. Severe non-hematologic toxicity was uncommon, with no intensive care admission or treatment-related death. At a median follow-up of 17 months, eight patients have relapsed and five have died of tumor progression. No statement can yet be made regarding adjuvant efficacy, but this high-dose regimen is very well tolerated. PMID- 7996069 TI - A case of mumps associated with acute hemolytic crisis resulting in hemoglobinuria and acute renal failure. AB - A 13-year-old boy presented with acute hemolytic anemia a few days after mumps infection. The ensuing hemoglobinuria resulted in acute renal failure in this child, which was corrected with fluid and alkali therapy. We draw attention to this uncommon complication of mumps and the need for careful evaluation. PMID- 7996068 TI - Hemorrhagic gastroesophageal ulceration by pulmonary infection in extrahepatic cholestatic pigs. AB - We developed a biliary and pulmonary microbiologic study in 22 Large-White pigs that underwent bile-duct ligation in order to demonstrate that sepsis has a biliary and pulmonary origin which may be involved in the gatroesophageal pathology. All the pigs died at 18.2 +/- 8.9 days of the post-operative period. The cause of death was hemorrhagic ulceration of the gastroesophageal region in 36.3% (n = 8) of the animals that also presented multiple bilateral miliary lung abscesses. High infestation rates with intestinal germs were found in the bile and lung. In conclusion, the experimental model of extrahepatic cholestasis in the Large-White pig could be useful for the study of etiopathogenic mechanisms by which the pulmonary infection produces a hemorrhagic gastroesophageal ulceration considered as stress ulcer. PMID- 7996071 TI - The problems with rule-based rationing. AB - Centralized, democratic rules are often asserted as a superior basis for rationing than individualized physician discretion. This article counters this prevailing wisdom by exploring the deficiencies of rule-based rationing. Rules are too imprecise to accurately reflect all the nuances of physical and mental impairment and the complexity of medical science, particularly considering the widely varying personal values that different patients attach to medical risk and benefit. Rule-based rationing also suffers from the biasing effects of interest group pressure on political processes and the tendency to absolve physicians from any moral responsibility for the rationing decisions they implement. Internalizing cost constraints is a more socially and professionally acceptable means of rationing and, in any event, it is inevitable since even a preponderance of rule-based rationing will leave considerable areas of discretion for physician judgment in the implementation and interpretation of the rules. As a consequence, despite the flaws of bedside rationing, it is foolhardy to dispense with it entirely in favor of an exclusively rule-based system. PMID- 7996070 TI - Oregon Health Plan: ration or reason. AB - The Oregon Health Plan gained national attention by changing the focus of health care from who is covered to what is covered. This change was facilitated by insurance reforms in the areas of small market, employer mandates, high risk pooling and Medicaid. Most controversial of the reforms is the use by the legislature of a prioritized list of health services to determine benefit levels for the insurance programs. Significant debate has occurred over whether the use of such a list is rationing or reasoning. The Oregon Health Plan represents a thoughtful and deliberate blending of fact with public value for the purpose of responsible health policy. It is that unique blending of public values developed through community participation with fact that focused the attention of the world on Oregon. PMID- 7996072 TI - Publicity and pricelessness: grassroots decisionmaking and justice in rationing. AB - The "grassroots turn" in bioethical discussions about justice in allocation of health care resources has attracted a great deal of support; in the absence of a convincing theory of justice in rationing, democratic decisionmaking concerning priority setting emerges with a kind of inevitability. Yet there remain suspicions about this approach--most importantly, worries about the socially corrosive impact of explicit, public decisionmaking that in effect sets a price on the lives of persons. These worries have been quieted, particularly by the work of Leonard Fleck, but not altogether stilled. I explore more sympathetically the ideals to which concerns about public rationing somewhat dimly respond, and suggest constraints on priority setting discussions which might accommodate those ideals rather better. PMID- 7996073 TI - Equality, explicitness, severity, and rigidity: the Oregon plan evaluated from a Scandinavian perspective. AB - This article is an attempt to evaluate the Oregon plan from the perspective of a Scandinavian national health care system. The Nordic welfare states are marked by a strong emphasis on equality. As an example of an egalitarian system we present the Norwegian health care model in part one. In part two, the arguments in favor of a one tier system in Norway are presented and compared to Oregon's two tier system. Although we argue, in part three, that a comparison of the degree of explicitness in the prioritization process shows that Norway has much to learn from Oregon, we do believe that the Norwegian system has some attractive elements that may function as an important corrective. In part four we present the Norwegian Guidelines for priority-setting and discuss the weight assigned to the severity of disease criterion. It is argued that the exclusion of information about the severity of disease partly explains the counterintuitive ranking of treatment-condition pairs in Oregon's initial method based on the principle of health maximization. A normative analysis of the conflicting norms of efficiency and equality of results is called for. The final part of the paper is devoted to the problem of rigidity. Henry J. Aaron has argued that the Oregon system is insensitive to inter-individual variations within each diagnosis-treatment pair. This objection is a severe one, since the system might end up treating patients unfairly on the individual level. To overcome this problem, we suggest a selection rule that should be more capable of dealing with the problem of rigidity. PMID- 7996074 TI - Just caring: Oregon, health care rationing, and informed democratic deliberation. AB - This essay argues that our national efforts at health reform ought to be informed by eleven key lessons from Oregon. Specifically, we must learn that the need for health care rationing is inescapable, that any rationing process must be public and visible, and that fair rationing protocols must be self-imposed through a process of rational democratic deliberation. Part I of this essay notes that rationing is a ubiquitous feature of our health care system at present, but it is mostly hidden rationing, which is presumptively unjust. Part II argues that the need for health care rationing is inescapable. Although Oregon is flawed as a model of health rationing, it gives us worthy moral lessons for health reform at the national level, which I analyze and defend in Part III. The most significant of these lessons is the importance of rational democratic deliberation in articulating fair rationing protocols for a community. In Part IV I sketch the philosophic justification for this approach and respond to some important criticisms from Daniels. PMID- 7996075 TI - The protection of laboratory animals: a response to Stephenson. AB - This paper clarifies certain issues raised by Wendell Stephenson (The Journal of Medicine and Philosophy 18: 375-388, 1993) about research programs and animal care practices at the Oregon Regional Primate Research Center. It also responds to Stephenson's critique of the National Institute of Health's Guide for the Care and Use of Laboratory Animals. It identifies utilitarianism as the ethical theory underlying Stephenson's critique. Arguing that such an ethical theory is unworkable in addressing concerns about biomedical research and the use of animals, the paper defends the Guide's reliance on a wider tradition of ethical theories. PMID- 7996076 TI - Osmium conductive metal coating for SEM specimen using sublimated osmium tetroxide in negative glow phase of DC glow discharge. AB - A new method of osmium conductive metal coating for scanning electron microscopy specimens using osmium tetroxide in direct current glow discharge and its apparatus have been devised. Anode and cathode plates are placed in a gas reactor, sublimated osmium tetroxide is introduced, and glow discharge is generated. As a result, the gas between the electrodes instantaneously becomes plasma. At the specimen surface, which is placed in the negative glow phase on the cathode plate, positively ionized osmium molecules are directly adhered and deposited, thereby leaving a completely amorphous metal coating of osmium. As a result, the formed coating precisely matched the fine structure of the specimen surface, and even when irradiated with a strong electron beam was free of heat damage, electrification and contamination. The secondary electron emission efficiency of the coating was also good. Furthermore, no granularity of the film surface was observed even when viewed at a high magnification. In this way, a superior osmium conductive metal coating was obtained. PMID- 7996077 TI - Immunolocalization of a Drosophila phosphatidylinositol transfer protein (rdgB) in normal and rdgA mutant photoreceptor cells with special reference to the subrhabdomeric cisternae. AB - Distribution of rdgB protein, which was recently shown to be a Drosophila phosphatidylinositol transfer protein, was studied in the photoreceptor cells of compound eyes of normal and rdgAPC47 mutant of Drosophila melanogaster by immunoelectron microscopy using (1) pre-embedding HRP staining, (2) pre-embedding NANOGOLD labeling followed by siliver enhancement, (3) and post-embedding colloidal gold labeling methods. In normal cells, immunoreactivity was localized to the membranes of subrhabdomeric cisternae (SRC) and adjacent plasma membranes at the bases of photoreceptive microvilli. In rdgAPC47 mutant cells, whose SRC gradually degenerate, the immunoreactivity in the plasma membranes at the bases of microvilli disappeared in parallel with the degeneration of SRC. Instead, the abnormally proliferated membranous structures became labeled by the antibody. These results indicate that the rdgB protein is normally localized to the SRC membranes and probably adjacent photoreceptive membranes, suggesting the involvement of the rdgB protein in the phosphatidylinositol transfer between SRC and photoreceptive membranes. PMID- 7996078 TI - Ultrastructural changes in glycerol-extracted skeletal muscle fibers after chemical modification of myosin heads with p-phenylenedimaleimide. AB - We examined the structural changes in relaxed glycerinated rabbit psoas muscle fibers induced by modification of the myosin heads with p-phenylenedimaleimide (p PDM), which reacts with sulfhydryls on the myosin head to cause its loss of ability to combine with actin and to hydrolyse ATP. In the longitudinal sections of both chemically fixed and quickly frozen muscle fibers, ladder-like structures, interpreted as the myosin heads extending nearly at right angles with the thick filaments, were more prominent in the p-PDM-modified fibers than in the control fibers. Fourier transform diffractograms of the longitudinal sections exhibited a distinct 14.3-nm meridional reflection, which arises from axial spacing of the myosin heads on the thick filament, in the p-PDM-modified fibers, but not in the control fibers. These results indicate that the p-PDM-modification of the myosin heads causes an increase in the regularity of myosin head arrangement on the thick filament. PMID- 7996079 TI - Effect of essential oils on the setting time of Kerr pulp canal sealer. AB - Setting times were determined for Kerr pulp canal sealer and the powder component of Kerr pulp canal sealer mixed with different liquid essential oils. The mean setting time of Kerr pulp canal sealer was 16.5 min. The mean setting times for the powder component of Kerr pulp canal sealer mixed with pure eugenol or for the standard liquid component of Kerr pulp canal sealer with rectified turpentine oil were 16.5 and 18.0 min, respectively. There was no significant difference in setting times among the three groups. The addition of rectified turpentine oil to the liquid component of Kerr pulp canal sealer did not have a significant effect on setting time. PMID- 7996080 TI - New electronic canal measuring device based on the ratio method. AB - The most striking disadvantage of most apex locators is that if there are electrolytes in the canal the meter shows a reading which is too short or sometimes the measurement itself becomes impossible. To overcome this drawback, a new concept for electrically measuring the root canal length has been developed. The device simultaneously measures two impedances of the canal using current sources with two different frequencies. Then the ratio between the two electric potentials proportional to each impedance is calculated. The quotient is shown on the device's meter and represents the position of a file tip in the canal. The present study found that the quotient was only negligibly influenced by the electrolyte present in the canal and decreased considerably as the file tip approached the apical foramen. PMID- 7996081 TI - Endodontic retreatment of Thermafil versus laterally condensed gutta-percha. AB - The Thermafil device is becoming a popular obturating material. Because endodontic failures inevitably occur with all techniques, questions of retreatment of Thermafil-obturated teeth will also arise. The purpose of this study was to compare retreatment of Thermafil and laterally condensed gutta percha. Thirty-five mandibular incisors were prepared with a stepback flare technique and divided into two groups. One group (n = 20) was obturated using Thermafil, the other group (n = 15) was obturated with laterally condensed gutta percha. The teeth were stored in a humidor for 3 months to allow sealer to set. Retreatment of both groups was accomplished using a combination of heat and chloroform solvent. The time for retreatment was recorded. The teeth were split longitudinally and the amount of gutta-percha remaining in the root canal was measured and analyzed statistically. The results showed that in the coronal one third of the canal, use of the Thermafil device resulted in significantly more remaining gutta-percha than use of laterally condensed gutta-percha. However, in the apical and middle one-third of the canal the difference in remaining gutta percha between Thermafil and laterally condensed gutta-percha was not significant. The metal carrier was easily removed and the mean time for retreatment was 6.3 min for Thermafil compared with 5.7 min in the lateral condensation group. PMID- 7996082 TI - Dentin permeability to bacterial proteins in vitro. AB - Passage of bacterial components through dentin is a subject of recent research with in vitro as well as with in vivo models. Diffusive transport of Porphyromonas gingivalis ATCC 33277 proteins has been demonstrated by the authors with an in vitro setup closely simulating the pulp chamber. The purpose of this investigation was to study the filtration of these proteins through dentin, measure possible concentration changes resulting from the filtering, and elaborate on the physical aspects of the binding process. The hydraulic conductance (Lp) of 10 dentin specimens was determined in three experiments using standard procedures: initially with phosphate-buffered saline, subsequently with a P. gingivalis ATCC 33277 suspension (200 micrograms/ml of protein), and finally with phosphate-buffered saline. The results showed significant, nonpermanent, alterations of the Lps of the dentin disks, and variable retention of the bacterial proteins among samples. A positive correlation between the bacterial protein retention and reduction of Lps was also demonstrated. The reduction of the Lps of the dentin samples was attributed to microstructural changes of the dentin, while the bacterial protein retention was considered to take place either on the surface of the disk or intratubularly. The intratubular interactions in the present experiment seemed to have a mechanical rather than a chemical basis. PMID- 7996083 TI - Apical seal of teeth obturated by the laterally condensed gutta-percha, the Thermafil plastic and Thermafil metal obturator techniques after post space preparation. AB - This in vitro study was conducted to determine the effect of post space preparation on teeth obturated with the Thermafil technique, both plastic and metal carriers, and the lateral condensation method. Three groups of 30 teeth each were obturated using the lateral condensation technique and the Thermafil plastic and metal techniques. Post space preparations were accomplished on the obturated groups. All specimens were submerged in India ink under a vacuum for 15 min and then soaked for an additional hour at atmospheric pressure. The teeth were decalcified and cleared to permit visualization and measurement of the extent of dye penetration. There was approximately three times more dye penetration in group 2 (plastic carrier) when compared with group 1 (lateral condensation) and group 3 (metal carrier). This was statistically significant at the 99% confidence level. PMID- 7996084 TI - Alteration of biological properties of bacterial lipopolysaccharide by calcium hydroxide treatment. AB - Bacterial lipopolysaccharide (LPS) plays a major role in the development of periapical bone resorption. Although the chemical properties of LPS are altered by treatment with an alkali such as calcium hydroxide, the effects of calcium hydroxide on the biological properties of LPS are not known. The purpose of this study was to investigate whether treatment of LPS with calcium hydroxide alters its biological action as measured by human monocyte secretion of prostaglandin E2. Monocyte cell cultures were stimulated with LPS or calcium hydroxide-treated LPS and culture supernatants were analyzed for prostaglandin E2 content using gas chromatography-mass spectrometry. Prostaglandin E2 was identified in supernatants of LPS-stimulated monocytes but not in those stimulated with calcium hydroxide treated LPS. It was concluded that the treatment with calcium hydroxide may alter biological properties of bacterial LPS. PMID- 7996085 TI - Dental pain evoked by hydrostatic pressures applied to exposed dentin in man: a test of the hydrodynamic theory of dentin sensitivity. AB - The hydrodynamic theory of dentin sensitivity holds that pain is evoked by stimuli producing minute shifts in tubule fluid. In human volunteers hydrostatic pressures were applied to prepared dentinal cavities. The subjects reported the magnitude and quality of their sensations of pain by means of an intermodal matching technique in combination with verbal descriptors. No pain could be elicited when the smear layer was present. After removal of this layer, pressure stimuli of either direction evoked sharp pain. Rapid changes in pressure induced higher pain intensities than slow changes, indicating that the dental A-delta system is dynamic and gradient dependent. These results provide support for the hydrodynamic theory of dentin sensitivity and also lend credence to the notion that the movement of fluid across dentin induces a selective activation of the A delta nerves in healthy pulps which is highly correlated with a sensation of sharp and/or shooting pain. PMID- 7996086 TI - Canal configuration in the mesiobuccal root of the maxillary first molar: a clinical study. AB - Surgical telescopes, headlamps, and a modified access preparation were used clinically to aid in the search for mesiolingual canals in the mesiobuccal roots of 208 maxillary first molars. In 148 (71.2%) of the mesiobuccal roots two canals were located and treated. Of these, 66 (31.7%) had two separate apical foramina (Weine Type III) and 82 (39.4%) had two canals that joined (Weine Type II). In 60 (28.9%) cases only one canal was located. PMID- 7996087 TI - Dens invaginatus: another use for the ultrasonic. AB - Dens invaginatus is an anomaly which has numerous and complex forms. Whenever endodontic therapy involving such a tooth becomes necessary, the clinician must be aware of the various treatment modalities available to facilitate proper care. Presented in this case report is a maxillary lateral incisor having the anomaly dens invaginatus in which both surgical and nonsurgical treatment was required. The surgical phase was facilitated through the use of ultrasonic instrumentation. PMID- 7996088 TI - Cast prosthesis removal using ultrasonics and a thermoplastic resin adhesive. AB - Nonsurgical endodontic procedures are routinely performed on teeth with existing cast restorations. The internal anatomy of the tooth and location of the root canals may be obscured by a crown or fixed partial denture. Tooth morphology and canal location may, therefore, be better visualized without the cast restoration in place. This article describes a conservative technique to remove an existing cast restoration to facilitate nonsurgical root canal treatment. PMID- 7996089 TI - Removal of fractured instruments using a combined automated/ultrasonic technique. AB - Removal of fractured instruments is one of the most difficult operative procedures in endodontics. Although a number of different devices and techniques have been developed, none are successful in all cases. An additional technique using an automated device (Canal Finder System) for bypassing and an ultrasonic device for loosening and retrieval of fractured instruments is presented. The rationale for this technique is described and illustrated by two clinical cases. PMID- 7996090 TI - Apical enlargement: influence on the sealing ability of the vertical compaction technique. AB - This study sought to evaluate the influence of apical enlargement on the sealing ability of vertical compaction. Sixty anterior teeth were used. Half of these teeth were prepared to a size 25 file and the other half to a size 40 file. Then vertical compaction was performed. Apical microleakage was determined using pressurized fluid filtration at 90 min, 6 h, 1 day, 4 days, and at 1, 2, 4, 8, 12, 16, and 24 wk after root canal obturation. Leakage tended to increase over time for both groups. The size 25 file group showed significantly less apical leakage than the size 40 file group. PMID- 7996091 TI - Comparison of apical leakage in root canals obturated with various gutta percha techniques using a dye vacuum tracing method. AB - In this study, residual apical microlumina remaining after obturation with five different gutta-percha obturation methods were traced with an efficient vacuum method. Seventy-nine human maxillary anterior teeth were instrumented and divided into five groups. The groups were obturated with single-cone techniques, lateral condensation, vertical condensation, Thermafil, and Ultrafil techniques. All specimens were immersed in a vacuum flask containing 2% methylene blue dye solution. The air was evacuated with a vacuum pump to an absolute pressure of 75 torr for 30 min. The roots were sectioned longitudinally and the linear extent of dye penetration was measured. Group mean linear dye penetration values were: single-cone technique, 1.55 +/- 0.95 mm; lateral condensation, 2.25 +/- 1.46 mm; vertical condensation, 2.61 +/- 2.61 mm; Thermafil 1.41 +/- 1.16 mm; and Ultrafil 3.51 +/- 4.70 mm. There were no statistically significant differences between the gutta-percha obturation methods. The clinical implications of these findings are discussed. PMID- 7996092 TI - Radiographic determination of canal length direct digital radiography versus conventional radiography. AB - This research compared the length determination images produced by Trophy and Regam direct digital radiographic systems with conventional E-speed radiographs. Size #15 K files were placed in the canals of 19 teeth of cadaver specimens and radiographed in a geometrically standardized bench device. Three evaluators estimated the length adjustment necessary to position the file at the apex. The mean estimated adjustment lengths were compared with the true, anatomically determined adjustment lengths. Statistical analysis with analysis of variance and the Student-Newman-Keuls test indicated no significant difference between direct digital thermal print images and conventional radiographs (p > 0.10). Length adjustment estimates with conventional radiographs were significantly more accurate than Regam high-resolution computer monitor images (p < 0.01). Additionally, it was determined that length adjustment estimates were significantly more accurate when the file was placed short of the apex (p < 0.001). The clinical relevance of these differences is discussed. PMID- 7996093 TI - Development of an in vitro culture system for the study of osteoclast activity and function. AB - Resorption is a difficult process to study in vivo because of the complex organization of mineralized tissue. The objective of this study was to develop an in vitro culture system for studying osteoclast attachment and activity. Transparent, microporous substrata were prepared using radio frequency-sputtering techniques to apply a thin layer of hydroxyapatite on polycarbonate filters previously coated with Type I collagen. Dentinoclasts isolated from the root surface of rat molar teeth undergoing inflammatory resorption and osteoclasts isolated from the endosteal surfaces of rat long bones were incubated on the experimental substrata. The culture system proved successful, supporting osteoclast viability and activity as demonstrated by cellular attachment and spreading seen by scanning electron microscopy. Activity was further demonstrated by monitoring acid production using a fluorescent probe, acridine orange. Isolated osteoclasts or dentinoclasts, when combined with synthetically prepared substrata, were observed to respond by mechanisms comparable to those that occur in vivo. Therefore, the system developed permits basic observations of osteoclasts in an in vitro system. PMID- 7996094 TI - Critical analysis of the balanced force technique in endodontics. AB - The "balanced force" technique was introduced in 1985 and it was reported that the resistance of the dentin, as it circumferentially contacted the flutes of a file in a curved root canal, would be sufficient to override and mask any tendency of the file to straighten during rotational instrumentation. An alternative mechanism based on compressive force and file flexure is presented in this article. In a laboratory study, the apical force necessary to cause files of sizes #10 to #70 to bend and conform to an average canal curvature was determined. These measurements were then related to the apical forces applied to teeth when utilizing the Balanced Force technique in a simulated clinical setting. It was then proposed that the apically directed force necessary to prevent coronal movement of the file and to effect dentinal shearing during counterclockwise rotation placed the file in compression, flexing it to conform to the curvature of the canal. This explanation was consistent with the experimental data for the files used in this study up to size #60 for an average canal curvature and for average instrumentation forces. PMID- 7996095 TI - In vitro comparison of various types of sodium perborate used for intracoronal bleaching of discolored teeth. AB - Fifty-eight extracted incisors were artificially stained to compare the efficacy of sodium perborate preparations used for intracoronal bleaching. All teeth were bleached for a 6-day period and the bleaching pastes replaced at days 1 and 3 (walking bleach technique). Sodium perborate-monohydrate, trihydrate, or tetrahydrate in conjunction with 30% H2O2 as well as tetrahydrate, either mixed with H2O or prepared as an experimental gel, were placed intracoronally at a level of 1-mm below the vestibular cementoenamel junction. Standardized slides were used to evaluate the color changes during bleaching. Success rates between 46 and 77% could be achieved, but no significant differences in final bleaching results between any of the sodium perborate types were observed. The use of the experimental gel resulted in comparable esthetic results (54%), although the portion of tetrahydrate in the gel was lower than that of the other preparations. In contrast to general recommendations that bleaching agents be left for 3 to 7 days in the access cavity before replacement, shorter bleaching intervals did not seem to affect the success. PMID- 7996096 TI - Placement accuracy of electrically conductive gutta-percha. AB - Conductive gutta-percha master cones (CGPMCs) with a surface conductive silver film have been developed for use with an electronic apex locator. Our research examined the accuracy of these CGPMC placed at working length (WL). Actual canal lengths of 30 extracted anterior teeth with mature apices were determined. Teeth were mounted in an in vitro system and canals step-back prepared. Each CGPMC was seated to the electronic WL as determined by the electronic apex locator and radiographs were made with the CGPMC in this position. Data showed (a) CGPMCs placed with the use of an electronic apex locator were at or within 1 mm short of WL in 36% of the teeth and (b) however, radiographic examination of the same CGPMC placements gave the appearance that 64% were at or within 1 mm short of WL. PMID- 7996097 TI - Effectiveness of various medications on postoperative pain following complete instrumentation. AB - The root canals of 588 consecutive nonsurgical patients with varying levels of pain were completely instrumented in 10 endodontic practices and 4 endodontic graduate programs. The participants were sequentially assigned to one of nine medications and a placebo. The severity of pain was assessed by the visual analog scale for 72 h following instrumentation. Among all of the parameters studied, three factors (preoperative pain, apprehension, and types of medication) were found to be significant in determining postinstrumentation pain. An association was found between the intensity of pre-and postoperative pain. As the intensity of preoperative pain increased, the chances for more severe postoperative pain increased (p < 0.0001). In addition, an association between the presence of apprehension before any treatment and postoperative pain was also noted (between 0.012 < p < 0.047). Examination of the time-effect curves for various medications in patients with no mild pain showed no statistical significant difference between the effectiveness of different medications and placebo. However, a multiple comparison of the effectiveness of various medications and placebo on patients in moderate and severe preoperative pain showed that ibuprofen, ketoprofen, erythromycin base, penicillin, and methylprednisolone plus penicillin were more effective than placebo within the first 48 h following complete instrumentation. PMID- 7996098 TI - A use of freeze-dried bone in endodontics. AB - A 40-yr-old man was referred for the treatment of a large bony lesion of the mandible proximal to the root apices of the lower left first molar. Treatment had been done 7 to 8 yr previous to the examination, and the fill appeared to be adequate. Treatment was curettement of the lesion, apical curettage, and filling of the lesion with sterile freeze-dried bone. The patient was seen 6 months later and reported that he had been asymptomatic and was very pleased with the treatment. A postoperative radiograph was taken at that time and it showed that there had been an ingrowth of healthy bone into the bony lesion and that only a small radiolucency at the mesial root remained. In only 6 months, a very large lesion of the mandible had almost completely resolved after using freeze-dried bone to act as a matrix for the ingrowth of new bone tissue. At 7 months postoperatively, another radiograph was taken which showed continued healing. PMID- 7996099 TI - Endodontic treatment in taurodontism. AB - This case report presents the successful endodontic treatment of a taurodontic mandibular second molar with five root canals (four in the mesial root, one in the distal root). PMID- 7996100 TI - Encouraging the highest quality in endodontic education. PMID- 7996101 TI - Cutting efficiency loss of root canal instruments due to bulk plastic deformation, surface damage, and wear. AB - Cutting efficiency loss of #15 H-type and K-type files was studied as a function of bulk plastic deformation and cutting edge wear. Instrumentation was done by purely extractive filing, without any significant torsional and/or bending strain. Cutting efficiency variations were assessed by means of cutting force measurement, while absolute cutting efficiency was obtained through three dimensional scanning stylus profilometry. Bulk plastic deformation-induced flute modifications may lower the cutting efficiency of H-type files by approximately 50%. For this instrument special care is required in tip and flute machining to avoid in vivo breakage. On the contrary, within the normal life-span of an instrument of approximately 100 strokes cutting edge wear is seen to be negligible. The existence of such wear is "inferred" indirectly from a 10% drop in extraction efficiency. PMID- 7996102 TI - Depth of penetration and appearance of Grossman sealer in the dentinal tubules: an in vivo study. AB - Five teeth extracted after chemomechanical preparation (group A) and 11 extracted 1 to 7 yr after endodontic treatment (group B) were selected for this study. A 1% NaOCl was used for irrigations and a lateral condensation technique with a Grossman-type sealer was used for obturation. The teeth were fractured and prepared for and viewed by a scanning electron microscope equipped with an electron dispersive spectrometer. All root canal walls of group A were covered with a thick smear layer. Sealer, either rod-like or granular in appearance and barium free, was present in the majority of the dentinal tubules of group B usually at a distance up to 200 microns from the root canal walls; in two cases up to 900 microns. Sealer was found deepest in the middle third of the root. The smear layer did not stop sealer from entering the dentinal tubules. The differences in the depth of penetration or in the appearance of the sealer cannot be attributed to the different time periods the teeth remained in the arch after endodontic treatment. PMID- 7996104 TI - Effect of IRM root end fillings on healing after replantation. AB - The effect of IRM as a root end filling placed in teeth prior to replantation was examined in 21 molar teeth in monkeys. After extraction, root ends were resected, the canals contaminated with oral bacteria, root end cavities prepared, and fillings of IRM or amalgam placed prior to replantation. After 8 wk the jaws were removed and prepared for histological examination. Bacteria were demonstrated in only 9 of 15 teeth filled with IRM; 18 of the roots (60%) were associated with inflammation, which was only moderate or severe around 5 (17%), and extended > 0.1 mm around only 2 roots. In contrast, of the 6 teeth filled with amalgam, all contained bacteria in the root canals and 11 roots were associated with moderate or severe inflammation, which around 8 roots extended > 0.5 mm. The difference in severity of inflammation for the two materials was statistically significant (p < 0.001). The tissue response to root end fillings of IRM in replanted teeth was less severe and less extensive than that to amalgam. PMID- 7996103 TI - Evaluation of the antibacterial effects of intracanal Nd:YAG laser irradiation. AB - Fifty canals of extracted single-rooted teeth were prepared to a size 50 master apical file, sterilized in ethylene oxide, and inoculated with a known quantity of Bacillus stearothermophilus spores. Five groups of 10 canals each were used. The control group received no treatment. The four treatment groups were exposed to pulsed Nd:YAG laser radiation or 0.5% NaOCl alone and in combination. The root canals were flushed with sterile distilled water to recover spores, and serial dilutions were incubated on blood agar and the number of colony-forming units recovered was determined. Analysis of the data indicated a 2-log reduction in colony-forming units among the four treatment groups as compared with the controls; however, no significant differences were observed among the treatment groups. In none of the treatment groups were the root canals sterilized. PMID- 7996105 TI - Polymerase chain reaction detection of human immunodeficiency virus DNA in human periradicular lesions. AB - Human immunodeficiency virus (HIV) has been previously reported to be present in the dental pulp of a patient with AIDS. The present report investigated the feasibility of polymerase chain reaction (PCR) amplification to detect the HIV proviral DNA in cells from periradicular lesions from an HIV-positive patient. The standard PCR amplification with 30 cycles and the nested PCR consisting of two 25-cycle amplifications were used. Samples from each reaction were separated by nondenaturing polyacrylamide gel electrophoresis and stained with ethidium bromide for visualization. Gels were electroblotted to nylon membranes, which were then fixed, denatured, and dried. Membranes were hybridized to specific radioactive oligonucleotide probes and placed next to Kodak XAR film for visualization of the HIV-specific bands. No evidence of HIV-specific reaction was observed in cells (negative control) or in two periradicular lesions from two HIV negative patients. The ethidium bromide strains revealed that PCR amplification of DNA extracts from two lesions from the HIV-positive patient yielded PCR bands (with both primer pairs) which corresponded to HIV-specific bands of the expected size. PMID- 7996106 TI - Osseous reaction to implanted ZOE retrograde filling materials in the tibia of rats. AB - The osseous reaction of IRM and EBA cement were studied utilizing an intraosseous implant technique in rats. Samples of IRM, EBA cement, and amalgam were placed into polyethylene tubes and subsequently introduced surgically into rat tibias. Specimens of each were evaluated histologically after 7, 14, 21, 56, and 100 days. The IRM and amalgam samples demonstrated essentially complete healing at 56 days. The EBA cement samples displayed a slightly greater inflammatory response up to the 56-day interval; however, they also showed complete healing by 100 days. A favorable osseous reaction was seen with both of these zinc oxide-eugenol materials. PMID- 7996107 TI - Torsional and stiffness properties of Canal Master U stainless steel and nitinol instruments. AB - The purpose of this study was to compare stiffness and resistance to fracture of stainless steel and nickel titanium Canal Master U instruments. Instruments sizes 20 through 50 were tested according to ANSI/ADA Specification No. 28. Resistance to fracture was determined by twisting and measuring the maximum torque and angular deflection (rotation) at the failure point. Stiffness was determined by measuring the moment required to bend the instrument 45 degrees. Stainless steel and nickel titanium Canal Master U instruments satisfied and far exceeded specification standards for stiffness. They also satisfied and far exceeded the standards for angular deflection at the failure point. Stainless steel Canal Master U met or exceeded the maximum torque at failure standards in all sizes except 50, whereas the nickel titanium instruments met the standards in all sizes except 45 and 50. The mechanical properties of nickel titanium, especially its low bending moment and high angular rotation at failure, encourage further evaluation with clinical studies. PMID- 7996108 TI - Relative frequency of teeth needing endodontic treatment in 3350 consecutive endodontic patients. AB - A survey covering 8 years and 3350 consecutive endodontic patients (1958 men (58%) and 1392 women (42%)) was conducted to determine the frequency of endodontic treatment for each tooth. At the time of initial examination, 3672 teeth required root canal therapy. Three hundred twenty-two patients needed endodontic therapy on multiple teeth. Posterior teeth were most frequently treated, 80.1% of the total with molars requiring 52.6% of the needed endodontic treatment. The mandibular first molar was treated most often, 18.8% of the time, followed by the maxillary first molar (13.5%) and the mandibular second molar (12.0%). The number of endodontically treated maxillary and mandibular teeth was similar, 50.8% and 49.2%, respectively. PMID- 7996109 TI - Apical marginal adaptation of orthograde and retrograde root end fillings: a dye leakage and scanning electron microscopic study. AB - A few studies have attempted to examine the correlation between clinical success of root canal therapy and in vitro examinations. In this case report we examined the apical adaptation of three orthograde fillings and four retrograde amalgam root end fillings from four radiographically successful teeth and one unsuccessful case by using dye leakage and scanning electron microscopic methods. Despite the radiographic appearance of successful root canal therapy, these examinations showed penetration of methylene blue dye through the apical foramina to the levels of the root canal filling materials in the roots treated nonsurgically and the presence of small gaps between filling materials and the dentinal walls. The methylene blue dye also penetrated through the interface between amalgam and root end cavities, and there were varying size gaps between the root end cavities and amalgam. Similar examinations on the radiographically unsuccessful retrograde filling showed the presence of gaps between the amalgam and the root end cavity preparation and complete penetration of methylene blue dye between amalgam, root canal filling materials, and the dentinal walls. PMID- 7996110 TI - Transillumination of the beveled root surface: an aid to periradicular surgery. AB - A technique utilizing fiberoptics to transilluminate a beveled root surface during periradicular surgery is described. This procedure when integrated with other standard endodontic surgical aids may help diagnose apical variations and vertical root fractures. PMID- 7996111 TI - Effectiveness of various medications on postoperative pain following root canal obturation. AB - This prospective study compared the effectiveness of nine medications and a placebo in controlling pain following obturation. A total of 588 patients who required root canal obturation were included. After obturation of root canals, each patient took one of the medications, salicylic acid (2 x 250 mg), acetaminophen (2 x 250 mg), ibuprofen (2 x 250 mg), ketoprofen (2 x 250 mg), acetaminophen (2 x 250 mg) plus codeine (2 x 250 mg), penicillin (2 x 250 mg), erythromycin base (2 x 250 mg), penicillin plus ibuprofen (2 x 250 mg), methylprednisolone (2 x 250 mg) plus penicillin (2 x 250 mg), or a placebo, every 6 h for 72 h. All medications were encapsulated in identical capsules. The patients registered their degree of discomfort on a visual analogue scale of 0 to 9. Statistical analysis of the data showed that the incidence of postoperative pain after obturation is lower than that following complete cleaning and shaping (5.83% versus 21.76%). In addition, there was no significant difference between the effectiveness of the various medications and placebo tablets in controlling postoperative pain following obturation. PMID- 7996112 TI - Interleukin-1 alpha and interleukin-1 beta periapical exudates of infected root canals: correlations with the clinical findings of the involved teeth. AB - This study quantified the concentrations of interleukin-1 alpha (IL-1 alpha) and interleukin-1 beta (IL-1 beta) in the periapical exudates obtained from 69 single rooted teeth using enzyme-linked immunosorbent assays, and examined their correlation with clinical findings of the involved teeth. Changes in the levels of these factors during root canal treatment were also investigated. The average levels of IL-1 beta (6.57 ng/ml) in periapical exudates were twice that of IL-1 alpha (3.25 ng/ml). The exudates containing pus showed significantly higher IL-1 alpha levels than those from the canals without pus (p < 0.01). The exudates from the canals with small radiolucent areas contained significantly higher IL-1 alpha levels than those from the canals with large radiolucent areas (p < 0.05). The tendency for there to be an increase in the levels of IL-1 alpha and a decrease in the levels of IL-1 beta was observed following root canal treatment. These observations suggest that IL-1 alpha and IL-1 beta are involved in the immunopathogenesis of periapical lesions and that IL-1 alpha and IL-1 beta may play different roles in the healing process of periapical lesions during root canal treatment. PMID- 7996113 TI - Dye penetration in root canals filled with AH26 in different consistencies. AB - It is recommended that the powder to liquid ratio of AH26 be very high and that the mixture be warmed to decrease viscosity before insertion into the root canal. In this study, the effectiveness of the powder to liquid ratio and temperature were assessed using 60 root canals of maxillary central incisors randomly divided into four groups after their cleaning and shaping. The teeth were obturated by either lateral condensation or the single-cone technique using AH26 warmed or at room temperature. After exposure to basic fuchsin, the teeth were embedded and cross-sectioned using a diamond saw. The dye penetration was measured microscopically and reported as a percentage of the total circumference of the filling of each slice using a goniometric eye-piece. After statistical analysis, it was concluded that AH26 in combination with lateral condensation leads to less leakage when used at room temperature. PMID- 7996114 TI - Comparison of three instruments in the preparation of the curved root canal using the modified double-flared technique. AB - Fifty-one extracted intact human first molar teeth with mature root apices were radiographed in a standardized way; their root curvature was determined and they were divided into three groups. One root canal in the mesial root of the mandibular molars, or the major mesiobuccal root in maxillary molars, was prepared with the modified double-flared technique, in one of three ways. The modified double-flared technique involves coronal flaring followed by working length determination and apical preparation. In group 1, unmodified tipped instruments (Flexofile) were manipulated with a balanced force technique. In groups 2 and 3, Flexogates files and Canal Master U files were operated in the manner recommended by the manufacturers. After preparation, the teeth were radiographed. The processed images of the root canals were traced using an image analysis computer software package. Comparisons were made between the preoperative and postoperative shapes of each root canal. A low viscosity polyvinyl siloxane was injected into the prepared root canals and the specimens were demineralized, dehydrated, and cleared. The preparation was evaluated subjectively according to desirable or undesirable criteria. The overall quality of preparation was rated. Statistical analysis showed that there was no significant difference in the overall change of area between the three groups (p = 0.994). There was a significant proportional increase in mesiodistal width in the coronal part of the canals in the Canal Master U group and more of the instruments in this group fractured.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7996115 TI - Placement of calcium hydroxide in simulated canals: comparison of glycerin versus water. AB - Calcium hydroxide (Ca(OH)2) is an intracanal medicament used as an antimicrobial agent, temporary obturant, and for apexification. Placement should be controlled for the maximum biological effect. This study evaluated and compared the effectiveness of delivery of Ca(OH)2 mixed with water or with glycerin as to (a) length of placement and (b) density of fill at different levels. Fifty-six simulated canals with moderate curvature were prepared to #60 using the step-back technique. Ca(OH)2 was mixed with either water (28 canals) or glycerin (28 canals) into a thick paste and placed with lentulo spirals. Radiographs were made and blindly assessed. Results showed that glycerin was statistically significantly superior (p < 0.05) to water as to (a) length of fill and (b) density in the coronal, middle, and apical thirds. Of particular interest was the apical third, in which 0% of water and 50% of glycerin Ca(OH)2 pastes were completely dense. PMID- 7996116 TI - An in vitro evaluation of plaster of Paris barriers used under amalgam and glass ionomer to repair furcation perforations. AB - Furcation perforations were created in the pulpal floor of 60 teeth and were repaired with amalgam alone, plaster of Paris under amalgam, light-cured glass ionomer alone, and plaster of Paris under light-cured glass ionomer. After the access openings were filled with composite resin, the teeth were immersed in 2% erythrocin B dye solution for 2 wk, sectioned longitudinally, and dye penetration was measured. The light-cured glass ionomer group provided the least amount of leakage, followed by the group of plaster of Paris under glass ionomer. The groups using amalgam alone and plaster of Paris under amalgam showed the most leakage. The plaster of Paris barrier prevented the overextension of the repair materials when used under amalgam and glass ionomer. PMID- 7996117 TI - Growth kinetics of fibroblasts on bovine dentin. AB - In vitro dentin barrier tests published so far show several shortcomings. Therefore, we designed a new test method using bovine dentin disks on which cells were grown on one side. In this study, we evaluated the growth kinetics of L-929 mouse fibroblasts on dentin disks of 0.75-mm thickness and 4-mm diameter derived from lower incisors of freshly slaughtered bovines. The application of 50% citric acid for 30 s was optimal for the gentle removal of the smear layer from the cut dentin slices. Growth kinetics of mouse fibroblasts depended on the initially plated cell density: optimal cell growth on the disks was observed with approximately 200 cells/mm2, which was the same as the growth rate on the bottom of a cell culture vessel. Consequently, bovine dentin disks are a suitable substrate for normal cell growth, and this set-up can be used in a dentin barrier test. PMID- 7996119 TI - Unusual pattern of pulp canal obliteration following luxation injury. AB - Pulp canal obliteration can occur as a result of tooth injury. A case report is presented in which a 6-yr-old patient developed partial pulp canal obliteration of a maxillary central incisor 9 months after luxation injury. The mineralization created unusual canal morphology which presented some difficulty in endodontic treatment of the tooth. PMID- 7996118 TI - Utilization of ketorolac tromethamine for control of severe odontogenic pain. AB - Ketorolac tromethamine (KT) (Toradol, 60 mg to 2 ml), an injectable nonsteroidal anti-inflammatory drug, was compared with a placebo (sodium chloride, 0.9%) for analgesic effects in patients presenting with severe odontogenic pain. Utilizing a double-blind protocol, KT and placebo were administered and evaluated. Forty patients presenting with severe odontogenic pain (75 to 100 mm and above utilizing the visual analog scale of 100 mm) recorded their visual analog scale score once every 10 min for 90 min after injection of either KT or placebo and before initiating traditional incision and drainage, endodontic therapy, and/or extraction. Results indicate that KT patients had significantly less pain from 20 to 90 min postadministration than those receiving placebo. By the 90-min period, KT patients were reporting negligible discomfort. Observed side effects included lightheadedness and injection site pain. It was concluded that KT effectively reduces severe odontogenic pain within 40 min after administration in human subjects, with minimal side effects. PMID- 7996120 TI - Visual lexical access is initially phonological: 2. Evidence from phonological priming by homophones and pseudohomophones. AB - Seven experiments were conducted that examined phonological and orthographic priming of naming using three- and four-field masking procedures with prolonged targets. Experiments 1-3 found significant phonological priming by homophones (TOWED-toad) that was independent of prime identifiability and prime-target stimulus onset asynchrony (SOA; 30, 60, or 250 ms). Subsequent experiments found significant phonological priming by pseudohomophones (TODE-toad) that was similarly independent of prime identifiability and SOA. Collectively, the limited effects of orthographic control primes (TOLD-toad, TODS-toad) and the pronounced and orthographically independent effects of phonological primes suggest (a) a leading role in visual word perception for a fast-acting, automatic, assembled phonology, and (b) a phonological basis, rather than an abstract graphemic basis, for the processing equivalency of letter variations. PMID- 7996121 TI - Working memory and retrieval: a resource-dependent inhibition model. AB - Four experiments examined individual differences in working memory (WM) capacity and how those differences affect performance on retrieval from both primary and secondary memory. The results showed that WM differences appear only in retrieval from primary memory and then only under conditions that lead to interference or response competition within the task. This suggests that WM capacity is important to retrieval that is based on controlled effortful search but not search that is based on automatic activation. A view is presented suggesting that individual differences in attentional resources lead to differences in the ability to inhibit or suppress irrelevant information. The paradigm also allowed more general comparisons between the processes involved in retrieval from primary and secondary memory. As expected, it was found that retrieval from primary memory was a function of set size. However, for sets larger than 2 items, retrieval from secondary memory was independent of set size. PMID- 7996123 TI - Two representational systems in dynamic visual identification. AB - How does the visual system retain and combine information about an object across time and space? This question was investigated by manipulating the spatiotemporal continuity and form continuity of 2 perceptual objects over time. In Experiment 1 the objects were viewed in central vision within a single eye fixation, in Experiment 2 they were viewed across a saccadic eye movement, and in Experiment 3 they were viewed at different spatial and retinal locations over time. In all 3 experiments some information about the object was found to be linked to its spatiotemporal continuity, and some information was found to be independent of spatiotemporal continuity. Form continuity was found to produce no effect. The results support a theory of dynamic visual identification according to which information is maintained over time both by episodic object representations and long-term memory representations, neither of which necessarily code specific sensory information. PMID- 7996122 TI - Effects of color on emotions. AB - Emotional reactions to color hue, saturation, and brightness (Munsell color system and color chips) were investigated using the Pleasure-Arousal-Dominance emotion model. Saturation (S) and brightness (B) evidenced strong and consistent effects on emotions. Regression equations for standardized variables were; Pleasure = .69B + .22S, Arousal = -.31B + .60S, Dominance = -.76B + .32S. Brightness effects were nearly the same for chromatic and achromatic colors. Blue, blue-green, green, red-purple, purple, and purple-blue were the most pleasant hues, whereas yellow and green-yellow were the least pleasant. Green yellow, blue-green, and green were the most arousing, whereas purple-blue and yellow-red were the least arousing. Green-yellow induced greater dominance than red-purple. PMID- 7996124 TI - Female reproductive profile in a fertile, genetically obese line of rats. AB - The female reproductive profile of a fertile genetically obese line of rats, named beta, is characterized. Hypophysis, ovaries, oviducts, and uteri weights do not differ from those of nonobese controls. Histological features in ovary, uterus, and vagina in beta line and alpha controls are similar, in agreement with classical descriptions in the subject. Vaginal opening, number of estrus, number of corpora lutea at ovulation time, and pregnancy patterns (i.e., ovary weight, number of corpora lutea, sites of implantation, and living fetuses, as well as productivity, fertility, litter size, and preweaning mortality) show no significant differences between obese and nonobese animals. From a reproductive standpoint, obese beta line would behave as nonobese. Up to now beta would represent the only fertile genetically obese line of rats, appearing as a profitable biological model to widen and deepen reproductive analysis on obesity. PMID- 7996126 TI - Down-regulation of integrin alpha 1/beta 1 expression and association with cell rounding in human cytomegalovirus-infected fibroblasts. AB - Human cytomegalovirus (HCMV) causes a c.p.e. characterized by rounding of the infected cell. Since interactions with the extracellular matrix may be involved in the cell rounding, we have analysed the expression of integrins, which are the main cell surface receptors involved in cell-substrate adhesion and spreading. By FACS analysis, a selective decrease in cell surface expression of alpha 1/beta 1 integrin was observed in HCMV-infected fibroblasts. This decrease coincides with cell rounding. Immunoprecipitation studies and FACS analysis of permeabilized cells have further demonstrated that total levels of this integrin are decreased in infected cells, suggesting that the reduction in cell surface alpha 1/beta 1 integrin is not due to a defect in transport to the surface. Furthermore, we have ruled out the possibility that the observed decrease in alpha 1/beta 1 expression is caused by a cytokine released from the infected cells by showing that the reduction is abolished by inactivating the HCMV with u.v. irradiation, and that conditioned medium from HCMV-infected cells has no effect on expression of alpha 1/beta 1 integrin in uninfected cells. Concomitant with the reduction in alpha 1/beta 1 levels, the HCMV-infected fibroblasts show a reduced ability to adhere to laminin and collagen IV. Taken together the data indicate that de novo synthesis of HCMV protein(s) causes a decreased assembly/expression of alpha 1/beta 1 integrin, coincident with the well characterized morphological alterations of the infected cell. PMID- 7996125 TI - Intracellular localization and DNA-binding activity of a class of viral early phosphoproteins in human fibroblasts infected with human cytomegalovirus (Towne strain). AB - Indirect immunofluorescence (IF) with monoclonal antibody M23 prepared against the nuclei of human embryo lung (HEL) cells infected with human cytomegalovirus (HCMV) Towne strain showed that the M23 antigen reactive with the M23 antibody was localized within distinct foci throughout the nucleus of infected HEL cells shortly after infection, even at 2 h post-infection (p.i.). The foci increased in size by 24 h p.i. and then the IF patterns changed to show the nuclear inclusion body-like structures at 72 h p.i. Treatment with phosphono-acetic acid, a HCMV DNA replication inhibitor, resulted in a nuclear pattern similar to that observed shortly after infection. The double-labelled IF test revealed that the HCMV UL44 antigen essential for viral DNA replication colocalized with the M23 antigen in the same intranuclear structure shortly after infection whereas neither viral antigen appeared to colocalize in most cells later after infection. The M23 antibody immunoprecipitated four proteins. 34K, 43K, 50K and 84K, in infected cells. To examine whether these proteins correspond to four early phosphoproteins encoded by the HCMV strain AD169 genome, the Towne strain DNA sequence corresponding to that encoding both the 34K and 43K proteins of strain AD169 was determined and transiently expressed in COS-7, Vero and HEL cells. These proteins were detected by the M23 antibody within the foci of these nuclei as found in the nuclei of productively infected cells shortly after infection. In addition, the 34K, 43K and 50K proteins at least were shown to be DNA-binding proteins by double- and single-stranded DNA-cellulose column chromatography. The relationship of these proteins to the status of viral DNA replication is discussed. PMID- 7996127 TI - Identification of structural domains within the large subunit of herpes simplex virus ribonucleotide reductase. AB - The large subunit (R1) of herpes simplex virus (HSV) ribonucleotide reductase is a bifunctional protein consisting of a unique N-terminal protein kinase domain and a ribonucleotide reductase domain. Previous studies showed that the two functional domains are linked by a protease sensitive site. Here we provide evidence for two subdomains, of 30K and 53K, within the reductase domain. The two fragments, which were produced by limited proteolysis and were resistant to further degradation, remained tightly associated in a complex containing two molecules of each. They were capable of binding the R2 subunit of HSV ribonucleotide reductase with approximately the same affinity as the intact protein but the complex did not complement the small subunit (R2) to give an active enzyme. At low concentrations (0.4 micrograms/ml) of trypsin or V8 protease, cleavage between the subdomains was prevented by the presence of the N terminal protein kinase domain. At higher protease concentrations (1 micrograms/ml) the N-terminal domain is extensively proteolysed and the 30K and 53K domains were generated. Identical results were obtained using purified R1 isolated from infected cell extracts or following expression in Escherichia coli. The origin of the two domains was investigated by N-terminal sequencing of the 53K fragment and by examining their reactivity with a panel of R1-specific monoclonal antibodies which we isolated and epitope mapped for that purpose. The trypsin cleavage site was found to lie between arginine 575 and asparagine 576, and proteolysis in this region was not prevented by the presence of R2 or the nonapeptide YAGAVVNDL. We propose that the ribonucleotide reductase region of HSV R1 exists in a two domain structure, and that the interdomain linking region is protected by the unique N terminus. PMID- 7996128 TI - Effects of herpes simplex virus type 1 infection on the plasma membrane and related functions of HeLa S3 cells. AB - In this study we evaluated modifications of various structural and functional properties of the plasma membrane of HeLa S3 cells following infection by the lytic virus herpes simplex virus type 1 (HSV-1). Na+/K(+)-ATPase activity considerably decreased during the first few hours post-infection (p.i.), whereas Na+ and K+ concentrations were not significantly affected until a much later period. By 8 h p.i., a partial membrane depolarization in infected cells had occurred, as indicated by a small change in the transmembrane potential. HSV infection induced a time-dependent lipid peroxidation of HeLa cell plasma membranes temporally correlated with the progressive reduction in Na+/K(+)-ATPase activity. Moreover, a significant decrease of membrane fluidity appeared at a late phase of the viral replicative cycle probably representing cumulative membrane damage. These results demonstrate that HSV-1 infection induced the production of free radicals in non-phagocytic cells. Since lipid peroxidation begins at an early stage of the virus replicative cycle, it may be directly related to viral cytopathicity. PMID- 7996129 TI - A putative non-hr origin of DNA replication in the HindIII-K fragment of Autographa californica multiple nucleocapsid nuclear polyhedrosis virus. AB - In addition to the seven known homologous regions (hrs) of Autographa californica multiple nucleocapsid polyhedrosis virus (AcMNPV) the HindIII-K fragment was also found to carry a putative ori, although this fragment does not contain an hr. Deletion analysis showed that this ori contains several segments essential for its activity and other 'auxiliary' sequences that enhance the ori activity. Sequence analysis identified several structures often found in other viral replication oris, such as palindromes and other repeated motifs. Although most of the auxiliary sequences of this ori were found to be deleted in the Bombyx mori nucleocapsid polyhedrosis virus genome, the essential part of this ori, containing the palindromes and the A/T-rich region, was retained. This and the fact that after prolonged serial passage of AcMNPV large replicating DNA molecules are found in which repeated sequences derived from the HindIII-K fragment accumulate are consistent with this region being a putative origin of AcMNPV DNA replication. PMID- 7996130 TI - Polydnavirus of the parasitic wasp Chelonus inanitus (Braconidae): characterization, genome organization and time point of replication. AB - Ultrastructural analysis of the polydnavirus of the braconid wasp Chelonus inanitus revealed that virions consist of one cylindrical nucleocapsid enveloped by a single unit membrane. Nucleocapsids have a constant diameter of 33.7 +/- 1.4 nm and a variable length of between 8 and 46 nm. Spreading of viral DNA showed that the genome consists of circular dsDNA molecules of variable sizes and measurement of the contour lengths indicated sizes of between 7 and 31 kbp. When virions were exposed to osmotic shock conditions to release the DNA, only one circular molecule was released per particle suggesting that the various DNA molecules are singly encapsidated in this bracovirus. The viral genome was seen to consist of at least 10 different segments and the aggregate genome size is in the order of 200 kbp. By partial digestion of viral DNA with HindIII or EcoRI in the presence of ethidium bromide and subsequent ligation with HindIII-cut pSP65 or EcoRI-cut pSP64 and transfection into Escherichia coli, libraries of 103 HindIII and 23 EcoRI clones were obtained. Southern blots revealed that complete and unrearranged segments were cloned with this approach, and restriction maps for five segments were obtained. Part of a 16.8 kbp segment was sequenced, found to be AT-rich (73%) and to contain six copies of a 17 bp repeated sequence. The development of the female reproductive tract in the course of pupal-adult development of the wasp was investigated and seen to be strictly correlated with the pigmentation pattern. By the use of a semiquantitative PCR, replication of viral DNA was observed to initiate at a specific stage of pupal-adult development. PMID- 7996131 TI - Adenovirus protein-protein interactions: hexon and protein VI. AB - A variety of mastadenoviruses were denatured, their polypeptides separated by electrophoresis on SDS-polyacrylamide gels and transferred to nitrocellulose. The immobilized polypeptides were washed, incubated with buffers containing hexons from human adenoviruses (Ad) types 2, 5 and 12 and the location of bound hexons was detected with anti-hexon antibodies. It was found that hexons from any of the three human adenovirus types bound to protein VI from all the mastadenoviruses examined. Furthermore we found that hexon-VI binding was significantly greater than the interaction between hexon and the precursor to VI, pVI. This binding was susceptible to detergents and to changes in pH or salt concentration. A rabbit polyclonal antibody was raised against a recombinant protein derived from the middle third of pVI from Ad2 and was used to quantify the difference in binding and to demonstrate the presence of a single intermediate (designated iVI) in the processing of pVI to VI. The affinity between iVI and hexon was considerably greater in our assay than that of pVI but was less than that between hexon and VI. A complementary binding of recombinant iVI to immobilized hexons was also demonstrated. This latter interaction, however, was only observed when hexon preparations were not boiled prior to electrophoresis, substantiating the proposition that the recognition motif on the hexon was conformation-dependent. These results are discussed in the context of understanding further the molecular basis of protein-protein interactions between the structural proteins of adenoviruses and the factors involved in virion maturation. PMID- 7996132 TI - Analysis of type-restricted and cross-reactive epitopes on virus-like particles of human papillomavirus type 33 and in infected tissues using monoclonal antibodies to the major capsid protein. AB - A panel of six monoclonal antibodies recognizing at least three different antigenic regions has been raised against the L1 major capsid protein of human papillomavirus type 33 (HPV-33), which is associated with cervical carcinoma. The antigenic sites defined by these antibodies have been mapped and classified as type-restricted or broadly cross-reactive using bacterially expressed L1 fusion proteins of a variety of HPV types. Conformational and linear epitopes have been distinguished using native and denatured virus-like particles. HPV infection of genital lesions has been analysed using both monoclonal antibodies and DNA amplification by PCR. The antibodies obtained should be useful to probe the structure of HPV capsids and to develop a general assay for the detection and classification of productive HPV infections. PMID- 7996133 TI - Mutations in the carboxy terminus of adeno-associated virus 2 capsid proteins affect viral infectivity: lack of an RGD integrin-binding motif. AB - Using site-directed mutagenesis, we tested whether a potential integrin-binding site, (composed of the amino acids RGD) which is predicted in the adeno associated virus 2 (AAV-2) capsid open reading frame (ORF), plays a role in the infectivity of AAV-2. Nucleotide sequencing of wild-type and mutant capsid protein-coding sequences, however, revealed discrepancies with the published sequence data at several positions, including a frameshift in the carboxy terminus which cancels the RGD motif and extends the capsid ORF by 27 amino acids. This sequence was confirmed by protein sequencing of proteolytic fragments of VP3. Thus, the virus mutant (pTAV-p), in which the intention was to exchange D of the putative RGD motif for E, resulted in replacing I480 by S in the newly established ORF. A second virus mutant (pTAV-d), in which the intention was to delete the RGD peptide, in fact gave a shift into the ORF of the originally published sequence. The pTAV-p mutant showed a strongly reduced infectivity compared to wild-type AAV-2, whereas pTAV-d was not infectious at all. Neither mutant accumulated viral ssDNA as detected by Hirt extraction. Analysis of virus particle formation and subcellular localization of the capsid proteins revealed a defect of the mutant capsid proteins in capsid assembly. This shows that the newly established C-terminal sequence of the AAV capsid proteins plays an important role in viral assembly. PMID- 7996134 TI - Molecular biology of rotaviruses. IX. Conservation and divergence in genome segment 5. AB - Nucleotide sequencing of RNA segment 5 from seven strains of group A rotavirus has been carried out to investigate the extent of diversity and conservation, as well as possible selective pressures involved in driving the fixation of sequence changes in this gene. Analyses of the derived sequences revealed that sequence conservation could not be correlated either with rotavirus serotype or the species of origin of the virus strain. These sequences together with other published and unpublished sequences of this gene have raised the total number available for comparison to 17. Alignment of all the available sequences revealed that only 88 amino acid positions (17.6%) in the protein encoded by gene 5 (VP5) are absolutely conserved but that the metal-binding motif reported by others is conserved in all sequences. Despite the high degree of sequence divergence, alignment of secondary structure predictions for VP5 showed a high level of conservation, suggesting that constraints on sequence divergence may operate at the level of overall higher-order structure of the encoded protein. PMID- 7996135 TI - Identification of the nucleic acid binding domain of the rotavirus VP2 protein. AB - The bovine rotavirus VP2 protein is the major component of the core and forms the most internal layer surrounding the dsRNA genome. We have constructed recombinant baculoviruses expressing truncated VP2 proteins. The nucleic acid binding activity of these truncated proteins was tested by North-Western blotting experiments with single-stranded and double-stranded probes. The nucleic acid binding domain in VP2 was localized between amino acids 1 to 132. Recombinant proteins bound single-stranded and double-stranded nucleic acids, but showed less affinity for double-stranded RNA and DNA. Interactions of VP2 with the genome were investigated in viral single-shelled particles by u.v.-cross-linking. In these experiments, only VP2 protein bound the genomic RNA in purified single shelled particles. PMID- 7996137 TI - Localization of Bunyamwera bunyavirus G1 glycoprotein to the Golgi requires association with G2 but not with NSm. AB - The Bunyamwera bunyavirus (BUN) M RNA genome segment encodes three proteins, two glycoproteins termed G1 and G2 and a non-structural protein called NSm, in the form of a polyprotein precursor that is co-translationally cleaved to give the mature proteins. Indirect immunofluorescence experiments have shown that these proteins localize to the Golgi complex in BUN-infected cells. We have used a recombinant vaccinia virus (vTF7-3), which expresses bacteriophage T7 RNA polymerase, to drive the expression of plasmids containing either the entire BUN M segment cDNA or fragments that encode the G1, G2 and NSm proteins separately under control of the T7 promoter. After transfection of these plasmids into vTF7 3-infected cells, correctly sized and processed proteins were detected by immunoprecipitation with BUN-specific antibodies. Immunofluorescence experiments showed that G1, G2 and NSm localized to the Golgi when transiently expressed from the full-length cDNA. When G2 or NSm were expressed separately they also localized to the Golgi, but when G1 was expressed alone a staining pattern typical for the endoplasmic reticulum was obtained. However coexpression of G2 and G1 from independent plasmids resulted in G1 localizing to the Golgi. In contrast translocation of G1 to the Golgi was not observed when G1 was coexpressed with NSm, although NSm itself was still detected in the Golgi. Similar results were obtained when the proteins were expressed from transfected plasmids containing the G2-, NSm- or G1-coding sequences under control of the cytomegalovirus immediate-early promoter. The localization of G1 to the Golgi when coexpressed with G2 was confirmed by the loss of endoglycosidase H (endo H) sensitivity of G1 after approximately 60 min in a pulse-chase experiment; G1 remained sensitive to endo H when expressed either alone or in combination with NSm. These results suggest that G2 contains the Golgi targeting and/or retention signals and that G1 has to interact with this protein to localize to this cellular compartment. PMID- 7996136 TI - Characterization of a virus variant produced by L cells persistently infected with lymphocytic choriomeningitis virus. AB - Continuous cultivation of murine L cells infected with lymphocytic choriomeningitis virus strain Armstrong leads to production of L(Arm) cells, which produce a predominantly cell-associated attenuated variant, the L(Arm) virus. The relatively few infectious particles that are released have lost the ability to form plaques on L cells and to cause illness in mice even if inoculated intracerebrally. Based on equal protein M(r)s, antigenicity and protein kinase activity, essentially identical results were obtained for the purified Armstrong and L(Arm) viruses. There was also no difference in production and release of particles with the potential to cause homologous interference. Such particles consisted of two types, one of which was highly susceptible to u.v.-irradiation, the other was highly resistant. In the case of the L(Arm) virus interfering particles, it appears that the u.v.-irradiation-susceptible forms represented infectious virus. Purified L(Arm) virus particles contained considerable quantities of subgenomic forms of (small) S- and (large) L-RNA and their complementary counterparts, which all appeared to be replicated autonomously in an unenriched manner. PMID- 7996138 TI - Classical swine fever: genetic detection and analysis of differences between virus isolates. AB - Two pairs of oligonucleotide primers were designed that specifically amplified regions of the classical swine fever virus genome. These products, corresponding to a 671 bp portion of the genes encoding the E1 and E2 (gp33 and gp55) proteins and a 1090 bp portion of the putative polymerase gene, were amplified from eight virus isolates which had been responsible for a series of classical swine fever outbreaks in Italy involving both domestic pigs and wild boar. For each virus the fragments were partially sequenced to give 475 bp of the E1/E2 glycoprotein and 212 bp of the putative polymerase gene sequences. The data from each set of fragments were compared with one another and with reference strains. This allowed us confidently to assign most of the viruses to one of three subgroups. An analysis of the same viruses with a panel of monoclonal antibodies was much less informative. The subgrouping of the isolates suggested that, in this region of Italy, there had been at least two separate introductions of classical swine fever over a 7 year period and that virus had been transmitted between domestic pigs and wild boar. A consensus nucleotide sequence derived from the glycoprotein fragments of all the viruses examined revealed conservation at the wobble position of some codons. PMID- 7996140 TI - Defective interfering type A equine influenza virus (H3N8) protects mice from morbidity and mortality caused by homologous and heterologous subtypes of influenza A virus. AB - Intranasal administration of defective interfering A/equine/Newmarket/7339/79 (H3N8) influenza virus (DI EQV) protected mice from otherwise lethal intranasal infection with homologous virus (EQV) or with the heterologous subtypes A/WSN (H1N1) or A/PR/8/34 (H1N1). Such protected mice showed little or no sign of clinical disease. Disease with only low mortality resulting from a 'low' dose of WSN was completely prevented with a 100-fold lower dose of DI EQV (4 haemagglutinating units/ml or 12 ng virus/mouse), indicating that there was a roughly proportional relationship between the protective dose of DI virus and the infecting inoculum. DI EQV-protected mice continued to gain weight at the normal rate, whereas those treated with inactivated DI EQV ceased putting on weight for about 7 days and were still underweight nearly 3 weeks later. Unlike DI WSN, DI EQV inhibited multiplication of infectious WSN in the lungs by 20 to 60-fold. Intranasal DI EQV on its own gave little protection to mice challenged 24 days later with EQV suggesting that it was only weakly immunogenic. DI EQV afforded significant protection when given up to 5 days before live virus challenge indicating that the DI genome remained active in the respiratory tract for this period of time. PMID- 7996139 TI - Analysis of NS3-mediated processing of the hepatitis C virus non-structural region in vitro. AB - The protease activity of the hepatitis C virus (HCV) NS3 protein has been investigated using transient expression methods in mammalian cells, as well as in vitro transcription/translation systems. We confirmed that expression of the NS3 5 polyprotein in rabbit reticulocyte lysates results in efficient cis processing at the NS3/NS4 junction. However, processing at the other predicted sites of NS3 mediated cleavage varied markedly in efficiency, the site most susceptible being that between NS5A and NS5B. Time-course analysis of the proteolytic processing of the HCV non-structural precursor showed that the cis cleavage between NS3 and NS4 occurred extremely rapidly. However, efficient cleavage at this position was dependent on the prior removal of the NS2 protein. Furthermore, the presence of uncleaved NS2 sequences on the enzyme severely impeded NS3-mediated proteolysis at downstream sites in the polyprotein. This suggests therefore that efficient cleavage at the NS2/NS3 junction is a pivotal event in HCV replication. During the course of this study a proteolytically inactive mutant of NS3 was characterized carrying a previously unreported amino acid substitution near the proposed active site of the enzyme. Molecular modelling suggested that the amino acid present at this position may influence the conformation of the active site of the enzyme. Recently a number of reports have described a second protease activity, located in the NS2/NS3 region, which is responsible for cleavage at the NS2/NS3 junction. We have identified an isolate of HCV, obtained from a U.K. patient, which has a virtually inactive NS2/NS3 protease. The possible implications of this observation are discussed. PMID- 7996141 TI - Identification of a second protein encoded by influenza C virus RNA segment 6. AB - Influenza C virus matrix protein (M1) is encoded by a spliced mRNA derived from RNA segment 6. Unspliced mRNA from this RNA segment, which has not been previously identified, can potentially encode a polypeptide that contains an additional 132 amino acids on the carboxy terminus of the M1 protein. Here the nucleotide sequences of RNA segment 6 of four influenza C strains, isolated in Japan between 1964 and 1988, were compared with the previously determined sequence of C/Ann Arbor/1/50. The results indicated that the deduced amino acid sequence of the carboxy-terminal 132 amino acid domain is conserved fairly well although it is more divergent than the M1 protein sequence. Examination of RNA segment 6-specific mRNAs also showed that unspliced mRNA is present, although in small quantities (approximately 13% of spliced mRNA), in influenza C virus infected cells. To search for a polypeptide encoded by the unspliced mRNA, the extra carboxy-terminal domain was expressed in Escherichia coli as the glutathione S-transferase fusion protein, and rabbit immune serum was raised against the purified fusion protein. Immunoprecipitation experiments with this antiserum revealed that a previously unrecognized protein of apparent M(r) approximately 18,000, designated CM2, is synthesized in influenza C virus infected cells. PMID- 7996142 TI - Increased binding activity of measles virus to monkey red blood cells after long term passage in Vero cell cultures. AB - Recent field isolates of measles virus (MV) obtained by using B95-8 cells have been reported not to agglutinate African green monkey red blood cells (AGM-RBC). Vero cell-adapted, plaque-forming strains derived from three field isolates at the third passage in Vero cell cultures (T8Ve-3, T11Ve-3 and N13Ve-3) also exhibited markedly decreased binding activity, as determined by infectivity absorption and haemadsorption tests. On the other hand, binding activity of the respective strains at the twentieth passage (T8Ve-20, T11Ve-20 and N13Ve-20) increased to practically the same level as that of the Edmonston strain, a standard strain of MV passaged long-term. A membrane immunofluorescence test revealed that the decreased binding activity to AGM-RBC of T8Ve-3, T11Ve-3 and N13Ve-3 was not due to decreased expression of the haemagglutinin (H) protein on the cell surface. The deduced amino acid sequence of the H protein synthesized in T11Ve-3-infected cells was identical to that in T11Ve-20-infected cells, although a single amino acid alteration was observed when T8Ve-3 was compared with T8Ve 20. Similarly, approximately half of the N13Ve-20-infected cells synthesized an H protein identical to that produced in N13Ve-3-infected cells, and nevertheless, exhibited markedly increased haemadsorption. The present results suggest that a viral protein(s) other than the H protein contributed to the binding activity of MV to AGM-RBC. PMID- 7996143 TI - Fusion properties of cells constitutively expressing human parainfluenza virus type 4A haemagglutinin-neuraminidase and fusion glycoproteins. AB - We established HeLa cell lines that constitutively expressed the fusion (F) and/or haemagglutinin-neuraminidase (HN) glycoproteins of human parainfluenza virus type 4A (PIV-4A) and used them to analyse the roles of these glycoproteins in virus-induced cell fusion. No syncytium formation occurred, even in HeLa cells expressing both the F and HN proteins (HeLa-4aF+HN cells). Also no syncytium was found in a mixed culture of cells expressing the F protein (HeLa-4aF) and the HN protein (HeLa-4aHN). Syncytia were observed in HeLa-4aF cells transfected with the HN gene, but no syncytium formation was found in HeLa-4aHN cells transfected with the F gene. Co-cultivation of HeLa-4aF+HN cells with HeLa-4aF cells generated large polykaryocytes, whereas co-cultivation with HeLa-4aHN cells induced no cell fusion. Infection of HeLa-4aF cells with PIV-4A generated large syncytia and degenerated nuclei, whereas little or no polykaryocytes were found in HeLa-4aHN cells infected with PIV-4A. From the above findings, the following conclusions were drawn: (i) the expression of both the F and HN proteins in the same cell is necessary for cell fusion; (ii) the expression of the F protein alone enhances susceptibility to cell fusion; (iii) the constitutive expression of the HN protein promotes resistance to paramyxovirus-induced cell fusion. PMID- 7996144 TI - Evidence that the paramyxovirus simian virus 5 can establish quiescent infections by remaining inactive in cytoplasmic inclusion bodies. AB - Following infection of BALB/c fibroblastic (BF) cells with simian virus 5 (SV5) only low levels of infectious virus were produced and the majority of cells survived the infection. However at 1 day post-infection (p.i.), near normal levels of all the virus proteins were synthesized and the virus genome was replicated. RNA analysis of the infected cells revealed that the levels of viral genomic RNA remained high over 5 days of infection, but that viral mRNA levels were significantly reduced by 3 days p.i. There was no evidence for the accumulation of defective genomes over this period. The reduction in mRNA levels was reflected by a concomitant decrease in the rate of ongoing viral protein synthesis. Despite the apparent decrease in viral transcription, comparative measurements of the relative levels of the different virus proteins at various times p.i. revealed that the levels of the P and NP proteins were similar at 1 and 5 days p.i. but the levels of V, M and F declined. Immunofluorescence analysis supported this data showing that at later times p.i., although there were some cells which were positive for all the viral proteins, a high proportion of cells were strongly positive for NP and P but negative for M, F and HN proteins. In these cells, NP and P were often located in discrete cytoplasmic foci. A series of cell lines were established from BF cells that had been infected at high multiplicity. Immunofluorescence studies showed that only a minority of cells in these cell lines were infected. This suggests that upon cell division, in a proportion of cells, virus replication was not taking place; otherwise it would be expected that all the daughter cells would remain infected. However, upon co-cultivation of these cells with Vero cells (cells that are fully permissive for SV5 replication), non-defective virus could be recovered. Virus cytoplasmic inclusion bodies could still be detected in a small proportion of BF cells that had been infected at high m.o.i. and passaged 10 times over a 12 week period, and again low levels of infectious virus could be recovered from these cells. It is proposed that in these persistently infected cells, the majority of virus genomes reside in an inactive form in cytoplasmic inclusion bodies but from which virus may occasionally be reactivated.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 7996145 TI - Evidence for two groups of banana bunchy top virus isolates. AB - Banana bunchy top virus (BBTV) DNA component 1 from isolates from 10 different countries was cloned and sequenced and the sequences were aligned and compared. This analysis indicated two groups: the South Pacific group (isolates from Australia, Burundi, Egypt, Fiji, India, Tonga and Western Samoa) and the Asian group (isolates from the Philippines, Taiwan and Vietnam). The mean sequence difference within each group was 1.9 to 3.0% and between isolates from the two groups was approximately 10%, but some parts of the sequences differed more than others. However, the protein encoded by the major open reading frame, which is probably a replicase, differed by approximately 5%. The region from the beginning of the stem-loop sequence to the potential TATA box was identical in all isolates except for a two nucleotide change in the Western Samoan isolate and a single change in that of the NSW isolate. These results, together with other evidence, suggest that BBTV has spread to bananas after the initial movement of bananas from the Asian Pacific regions to Africa and the Americas. PMID- 7996146 TI - Papaya ringspot potyvirus: isolate variability and the origin of PRSV type P (Australia). AB - We have sequenced the coat protein gene of nine isolates of papaya ringspot virus (PRSV) including six Australian and three Asian isolates and compared these with four previously reported sequences of PRSV. There was up to 12% sequence variation between isolates at the nucleotide level. However, there was no significant difference between the sequences obtained from Australian isolates irrespective of whether they were PRSV type P (cucurbit or papaya infecting) or PRSV type W (cucurbit infecting) and these isolates were more closely related to one another than to any other isolate. These results imply that PRSV-P, first recorded in Australia in 1991, arose locally from PRSV-W (first recorded in Australia in 1978) rather than being introduced. Further, there was no consistent sequence difference between PRSV-P and PRSV-W isolates that would obviously account for their host range difference. PMID- 7996147 TI - Capsid protein properties of cowpea aphid-borne mosaic virus and blackeye cowpea mosaic virus confirm the existence of two major subgroups of aphid-transmitted, legume-infecting potyviruses. AB - A study of the capsid proteins of different legume-infecting potyviruses using specific monoclonal antibodies on immunoblots of crude extracts from infected plants revealed that cowpea aphid-borne mosaic virus (CAMV) and blackeye cowpea mosaic virus (BICMV) have coat protein M(r) values of 32K and 35K, respectively. Immunoblot comparisons of BICMV, peanut stripe mosaic virus (PStV), bean common mosaic virus (BCMV) and azuki bean mosaic virus (AzMV) revealed equal reactivity of their 35K coat proteins. Similar comparisons between CAMV and the necrotic strain of BCMV (isolate NL3) showed a serological relationship between their 32K coat proteins, results providing the first evidence of a possible similarity between CAMV and BCMV NL3. Peptides from trypsin digests of the coat proteins of several of these legume-infecting potyviruses were analysed by HPLC. Comparison of the peptide profiles confirmed the serological results in distinguishing the two subgroups. Peptide profiles of coat protein from BICMV, PStV, AzMV and BCMV were almost identical, results suggesting that they could be considered as strains of one virus. In contrast, peptide profiles of various CAMV serotypes and BCMV NL3 were distinct from the first group and exhibited limited similarities to each other. PMID- 7996148 TI - The nucleotide sequence of potato mop-top virus RNA 2: a novel type of genome organization for a furovirus. AB - Particles of isolate T of potato mop-top furovirus (PMTV) contain three RNA species (6.5, 3.0 and 2.5 kb). Hybridization tests with cloned cDNA probes showed that none of these species was derived from another. RNA 2 (2962 nt), which was sequenced, has non-coding regions of 368 nt and 285 nt at the 5' end and 3' end, respectively. Near the 5' terminus, nucleotides 46 to 110 are able to form a stem loop structure, the stem of which has 23 bp with only one mismatch and one unpaired nucleotide. From the 5' end, the four open reading frames encode proteins of 51K, 13K, 21K and 8K. The first three of these have sequence similarity to the triple-gene-block proteins of other viruses, particularly barley stripe mosaic hordeivirus. The 51K protein contains a putative NTP-binding motif and the 13K and 21K proteins each contain two hydrophobic regions separated by a hydrophilic region. The 8K protein is rich in cysteine. PMTV differs from other furoviruses in having a tripartite genome. Its RNA 2 differs in gene content from the RNA 2 of soil-borne wheat mosaic virus, which lacks a triple gene block, and from that of beet necrotic yellow vein virus, which has a coat protein gene and read-through domain to the 5' side of its triple gene block. The gene arrangement in PMTV is therefore novel for a furovirus. PMID- 7996149 TI - Nucleotide sequence of RNA 1, the largest genomic segment of rice stripe virus, the prototype of the tenuiviruses. AB - The complete nucleotide sequence of RNA 1, the largest genomic segment of rice stripe virus (RSV), was determined using two sets of overlapping cDNA clones. RNA segment 1 comprises 8970 nucleotides and on the viral complementary sequence has a single long open reading frame coding for a protein of 2919 amino acids with an estimated M(r) of 336860. Amino acid sequence comparisons of the putative protein indicated strong homology (30% amino acid identity over about 1500 residues) with the L protein of the genus Phlebovirus of the Bunyaviridae, but no detectable similarity with other members of the Bunyaviridae. However, weak similarity was detected with the L protein of Tacaribe arenavirus. The highly homologous sequence domain includes the conserved motifs of the putative RNA-dependent RNA polymerase. The data presented here, along with previous work clearly show significant similarities in genome organization, structure and expression between RSV and members of the genus Phlebovirus of the Bunyaviridae. Taken together, we propose that tenuiviruses should be included in the Bunyaviridae under the genus Tenuivirus. PMID- 7996150 TI - Nucleotide sequence and structural features of the group III citrus viroids. AB - The nucleotide sequence and secondary structure of two representative variants from the Group III citrus viroids. CVd-IIIa (297 bases) and CVd-IIIb (294 bases) were determined. The variants are related to the apple scar skin viroid (ASSVd) family. Although smaller in size than any of the ASSVd-related viroids, the central conserved region as well as most of the terminal conserved region of ASSVd is retained. The rod-like structural configuration (characteristic of ASSVd) of the variants as predicted by minimum free energy analysis is presented. PMID- 7996151 TI - The closely related citrus ringspot and citrus psorosis viruses have particles of novel filamentous morphology. AB - Some properties of the particles of citrus ringspot virus (CtRSV) and the related citrus psorosis-associated virus (CPsAV) are described. The particles of CtRSV have been reported to be sinuous linear structures about 10 nm in diameter and of two lengths (300 to 500 nm and 1500 to 2500 nm) representing 'top' and 'bottom' sedimentation components. We show that these particles are collapsed double stranded forms of nucleocapsid-like, highly flexuous open circles formed of filaments 3 to 4 nm in diameter. Top-component filaments had contour lengths of 600 to 1000 nm, i.e. twice that reported for the corresponding collapsed form. Bottom-component filaments had contour lengths about four times longer than those of top-component filaments. The structures suggest that CtRSV represents a new genus (possibly family) related to the tenuiviruses. However, we failed to demonstrate any serological relationship between CtRSV and several tenuiviruses; moreover, the capsid protein sizes and host ranges are quite different. We offer the name Ophiovirus for the proposed new genus. PMID- 7996152 TI - Identification of an amino acid change that affects N protein function in vesicular stomatitis virus. AB - TsW16B is a temperature-sensitive mutant of vesicular stomatitis virus. Others have shown that it is temperature-sensitive for replication in vivo and for transcription in vitro and that these phenotypes are probably due to mutation of the N (nucleocapsid) gene. Five independent revertants were isolated from tsW16B based on their ability to grow at 39 degrees C. The thermosensitivity of in vitro transcription by these revertants was similar to that of the wild-type virus [wt(HR)] from which tsW16B was derived. Fractionation-reconstitution studies of two revertants indicated that the reversion was in the N or P (phosphoprotein) gene. The N and P genes of wt(HR), tsW16B, and these two revertants were sequenced. There were no differences between the P genes. Comparison of the predicted N protein sequences of wt(HR), tsW16B and the two revertants indicated that the growth and in vitro transcription phenotypes of tsW16B were due to a change of amino acid residue 238 from threonine to isoleucine. The amino acid at position 238 in the other three revertants also showed an exact reversion to threonine. Amino acid residue 238 lies in a domain of the N protein which is highly conserved among vesiculoviruses. PMID- 7996153 TI - Molecular cloning and sequence analysis of the phosphoprotein, nucleocapsid protein, matrix protein and 22K (M2) protein of the ovine respiratory syncytial virus. AB - Respiratory syncytial viruses (RSVs) cause serious respiratory tract disease in infants and children worldwide and similar disease in calves. Strains have been isolated from other ruminant animals such as sheep and goats, but these viruses have not been characterized at the molecular level. In this study, we report the cloning and sequencing of four structural genes coding for the phosphoprotein, nucleocapsid (N) protein, matrix (M) protein and 22K protein of an ovine RSV strain. Comparisons of these sequences with those of bovine and human RSV show that the M and N proteins are the most conserved between ruminant RSV strains and the N protein is the most conserved protein between human and ruminant RSV strains. The attachment G glycoprotein and the small hydrophobic protein are the most divergent proteins among human and ruminant RSV subgroups. PMID- 7996154 TI - Nucleotide sequence comparisons of the fusion protein gene from virulent and attenuated strains of rinderpest virus. AB - We have cloned and sequenced the entire fusion (F) protein gene of the RBOK vaccine strain of rinderpest virus and the coding regions for the F genes of two mild field isolates of the virus from Africa. Analysis of the nucleotide and the predicted amino acid sequences showed that the vaccine virus was more than 99% identical in the protein coding region to the virulent Kabete O strain from which it was derived, whereas the field isolates differed by 10 to 12% from each other and from the vaccine strain. No changes were found in the F protein which could explain attenuation of the vaccine; however, each of the mild field isolates had amino acid changes in important functional areas which may be related to their attenuated phenotype. PMID- 7996155 TI - Genetic reassortment of influenza C viruses in man. AB - We reported previously that the antigenicity of the haemagglutinin-esterase (HE) glycoprotein of the human influenza C virus strain C/Nara/1/85 was indistinguishable from that of strain C/Nara/82. However, the ribonuclease T1 oligonucleotide map of total virion RNA of C/Nara/1/85 differed remarkably from the map of C/Nara/82, resembling instead the map of C/Nara/2/85, which has an HE antigenicity dissimilar to C/Nara/82 and C/Nara/1/85. This observation raised the possibility that C/Nara/1/85 might have arisen by reassortment from two viruses closely related to C/Nara/82 and C/Nara/2/85, respectively. Here, we compared the total nucleotide sequence of the HE gene and partial sequences of the other genes of C/Nara/1/85 with those of C/Nara/82 and C/Nara/2/85. The results suggest that C/Nara/1/85 has inherited HE and NP genes from a C/Nara/82-related virus and the PB2, PB1, PA, M and NS genes from a C/Nara/2/85-related virus. PMID- 7996156 TI - Nucleotide sequence of hepatitis C virus (type 3b) isolated from a Japanese patient with chronic hepatitis C. AB - The genomic sequences of many hepatitis C virus (HCV) isolates have been reported and a variety of virus genotypes have been classified based on homology in the conserved regions. We have previously identified five distinct genotypes (1a, 1b, 2a, 2b and 3b) in Japanese patients with chronic HCV infection by comparing the sequences of the NS5 region. The complete nucleotide sequence for five genotypes (1a, 1b, 1c, 2a and 2b) have already been reported and we report here the complete nucleotide sequence of genotype 3b. The isolate (HCV Tr) was 9439 nucleotides long, excluding the poly(U) tract at its 3' end, and encodes a single long open reading frame of 3023 amino acids. Total nucleotide sequence homologies were 68.4 to 68.7%, 68.3 to 69.0%, 67.2%, 65.8% and 65.6% compared with type 1a, 1b, 1c, 2a and 2b genomes, respectively. The amino acid sequences of these five genotypes were highly homologous in the core, NS3 and NS5B regions, but the E2/NS1 region, which contains hypervariable regions 1 and 2, and the NS5A region were poorly conserved. Although it was possible to detect antibody against the relatively homologous core and NS3 regions by ELISA, the presence of divergent protein structures must be taken into account in the development of a vaccine. PMID- 7996157 TI - Cloning, characterization and expression of the gene that encodes the major neutralization-specific antigen of African horsesickness virus serotype 3. AB - The gene encoding the outer capsid protein, VP2, of African horsesickness virus serotype 3 (AHSV-3) has been sequenced in its entirety from cDNA clones of the segment 2 RNA, and compared with the previously published VP2 gene sequence of AHSV-4. AHSV-3 genome segment 2 was shown to be 3221 nucleotides in length, encoding a protein of 1057 amino acids with a 50.5% identity to the amino acid sequence of AHSV-4 VP2. Two areas of high variability (approximately 35% identity) were identified. The N-proximal variable region (amino acids 128 to 309) exhibited significant hydrophilicity, suggesting a possible role in the determination of the serotype-specific immune response. VP2 of AHSV-3 has furthermore been expressed in a baculovirus expression system. The expressed protein was shown to react specifically with an anti-AHSV-3 serum in Western blots. Antibodies raised in rabbits and guinea-pigs against the recombinant VP2 neutralized the virus in a plaque reduction assay, confirming the identity of VP2 as the major neutralization-specific antigen of AHSV. PMID- 7996159 TI - Virus neutralization reveals antigenic variation among feline immunodeficiency virus isolates. AB - By using a focus reduction assay in CrFK feline fibroblast cells, virus neutralizing antibodies (VNA) to feline immunodeficiency virus (FIV) were demonstrated in cats that had been naturally or experimentally infected with FIV. The antigenic relatedness of four strains of FIV, divergent in nucleotide sequence within the env gene, was investigated by neutralization following adaptation of each virus for growth in CrFK cells. Two of the viruses were from The Netherlands (FIV/AM-4 and AM-6), one was from the U.K. (FIV/GL-8) and one was from the U.S.A. (FIV/PET). Reaction of the viruses in the neutralization assay with cat antibodies to homologous or heterologous strains indicated that while there was a degree of cross-reactivity between all four, there were consistent differences suggesting the existence of FIV neutralization subtypes. In particular, FIV/PET and FIV/AM-6 were closely related but FIV/PET and FIV/GL-8 were clearly distinct. VNA from naturally infected cats in the field showed a pattern of reactivity against FIV/PET and FIV/GL-8 that confirmed the antigenic diversity of FIV. PMID- 7996158 TI - Genetic analysis of NSP1 genes of human rotaviruses isolated from neonates with asymptomatic infection. AB - The nucleotide sequences of the genomic RNA segments 5 (gene 5) encoding the non structural protein NSP1 of rotavirus strains M37 and ST3, isolated from neonates with asymptomatic infection, were determined. The sequences were similar overall (95% identity) as were the deduced amino acid sequences of NSP1 (93%). However, the M37 and ST3 NSP1 proteins shared only 82% and 81% identity, respectively, with the corresponding protein from another strain isolated from a neonate with asymptomatic infection (I321). Differences (of between 15% and 31%) were found in comparison with NSP1 sequences of rotaviruses isolated from older children with symptomatic infection (Wa, DS1 and IGV-80-3). Using an M37 gene 5-derived probe, Northern hybridization analysis of total genomic RNA extracted from viruses isolated from older children (Wa, RV4, RV5 and P) and neonates (M37, ST3, RV3 and 1076), representatives of the most common human G and P types, further indicated that while the gene 5 alleles of strains M37, ST3 and RV3 had a high degree of identity, no significant identity between 1076 and M37 was observed. In addition, cross-hybridization between the M37 probe and RNA of strains from older children (Wa, RV4 and P) was evident. Thus, neonatal human rotavirus strains do not carry a common NSP1 gene. PMID- 7996160 TI - Feline immunodeficiency virus can productively infect cultured endothelial cells from cat brain microvessels. AB - Feline immunodeficiency virus (FIV) provokes a disease in cats characterized by histopathological lesions similar to those observed in AIDS patients. In order to determine whether endothelial cells from brain microvessels are involved in the central nervous system disease to the same extent as macrophages and microglia, cells were isolated from healthy cat brains, cultured and infected in vitro with the FIV Villefranche IFFA 1/88 strain. The isolated cells displayed typical endothelial cell ultrastructural features and were characterized further by von Willebrand factor-labelling and the binding of specific lectins such as Ulex europaeus lectin on their membrane. They were also able to take up acetylated low density lipoproteins. Two weeks after infection, significant amounts of FIV p24 antigen were detected by indirect immunofluorescence in syncytia and single cells. Concomitantly, the same antigen could be detected in the culture medium of the infected cells by an ELISA technique. Numerous viral particles as well as different steps in the process of viral budding were observed under transmission electron microscopy. The synthesis of FIV p24 antigens still occurred in cells in which replication was blocked in the G2 phase with taxol. Our results suggest the possibility of a productive infection of brain microvascular endothelial cells by FIV in vivo, which could lead to important perturbations in the functions of the blood-brain barrier. PMID- 7996161 TI - Phylogenetic classification of human T cell leukaemia/lymphoma virus type I genotypes in five major molecular and geographical subtypes. AB - Proviral DNA was obtained from ex vivo peripheral blood mononuclear cells of 75 human T cell leukaemia/lymphoma virus type I (HTLV-I)-infected individuals who were either asymptomatic or had adult T cell leukaemia or tropical spastic paraparesis/HTLV-I-associated myelopathy. Amplified long terminal repeats (LTRs) were analysed for restriction fragment length polymorphisms (RFLPs). The results, together with previously published LTR data (a total of 180 specimens analysed), showed the presence of 12 different RFLP profiles with four major molecular subtypes. Furthermore, a fragment of 413 bp (nucleotides 22 to 434) of the U3/R region was sequenced for 12 new HTLV-I specimens originating from Central and West Africa (8 cases), Iran (1 case), Caribbean (2 cases) and Reunion Island (1 case). Phylogenetic analysis using three different techniques (maximum parsimony, neighbour-joining and UPGMA) comparing these 12 strains (including four new African HTLV-I variants) with the 30 published partial HTLV-I LTR sequences (nt 120 to 434) showed the existence of clusters of molecular variants in discrete geographical areas. The topology of the phylogenetic trees is thought to reflect HTLV-I evolution and the migrations of virally infected populations in the recent or distant past. Furthermore, there was a nearly perfect concordance between the clustering based on the LTR sequence homologies and the LTR RFLP subtypes suggesting that this rapid and simple technique is well suited to the investigation of HTLV-I molecular epidemiology. These results allow a new phylogenetic classification of HTLV-I genotypes into five major molecular subtypes: Cosmopolitan (C) subtype widespread all over the world, Japanese (J) subtype, West African (WA) subtype. Central African (CA) subtype and Melanesian (M) subtype. PMID- 7996162 TI - The granulin gene region of Cryptophlebia leucotreta granulosis virus: sequence analysis and phylogenetic considerations. AB - The nucleotide sequence of a 2.2 kb genome region of the baculovirus Cryptophlebia leucotreta granulosis virus (CIGV) encompassing the granulin gene and a second open reading frame, designated ORF909, was determined. The putative granulin ORF comprises 744 nucleotides encoding a polypeptide with a predicted M(r) of 29.3 K. The 5' leader of the granulin gene contains a canonical late baculovirus promoter (ATAAG) and differs only in two nucleotide positions from the sequence of Cydia pomonella granulosis virus (CpGV). Sequence comparison with the granulin genes of different granulosis viruses indicated a very close relationship between CIGV and CpGV of about 96% amino acid identity. ORF909 is 909 nucleotides in length and encodes a potential protein of M(r) 36.2K. It contains two zinc finger-like motifs, similar to ME53, which was previously described for Autographa californica multiple nucleocapsid nuclear polyhedrosis virus. ORF909 protein is significantly shorter than ME53 protein, lacking more than 105 amino acids of the amino terminus of ME53. Both genes contain an early and a late promoter motif suggesting a similar temporal regulation. Homologous sequences to ORF909 are also present upstream of the granulin genes of other granulosis viruses (GVs) indicating that this ORF is common in GVs. PMID- 7996164 TI - Midwifery and child health in Nepal. PMID- 7996165 TI - Theoretical perspectives on the nature of social support in cardiovascular illness. AB - In light of the minimal follow-up care that cardiovascular patients typically receive and the few patients who enter cardiac rehabilitation programs, it is evident that these patients need more support resources to improve their health outcomes. A better understanding is needed of the basic support processes that occur after a cardiac event so that the different sources and types of support can be tapped for the desired outcome. This article highlights the research findings on social support for cardiovascular patients in light of various theoretical perspectives and provides implications for practice and future research. PMID- 7996163 TI - ICP34.5 influences herpes simplex virus type 1 maturation and egress from infected cells in vitro. AB - We have previously demonstrated that efficient replication of mutant herpes simplex virus which fails to synthesize the polypeptide ICP34.5 is cell type and cell state dependent. ICP34.5 negative viruses do not grow in stationary state mouse embryo fibroblast 3T6 cells whereas the growth kinetics in BHK cells are indistinguishable from those of wild-type. We now demonstrate that this defect is not due to an inability of mutant virus to adsorb to 3T6 cells but rather to an inability to spread from the initially infected cells. Electron microscopic studies with wild-type HSV in both BHK and 3T6 cells revealed virus particles equally distributed between nucleus and cytoplasm, and additionally in the extracellular matrix. In BHK cells infected with the ICP34.5 negative mutant 1716, virus is likewise distributed between nucleus and cytoplasm but in 50% of the infected cells there is marked delamination and swelling of the nuclear membrane. In addition there is evidence of a significant number of particles trapped between the nuclear lamellae. When 1716 is used to infect 3T6 cells, over 90% of the virus particles are confined to the nuclei and the number of infected cells remains constant between 24 and 48 h with no increase in the proportion of extracellular virus. Failure to express ICP34.5 appears therefore to result in a defect in virus maturation and egress from the nuclei of infected cells. Egress of HSV from the nuclei to the extracellular space is thought to occur via two pathways. We postulate that lack of expression of ICP34.5 results in one of these pathways being blocked. In BHK cells this leads to overloading of the alternative pathway with a buildup of particles in the nuclear lamellae and associated endoplasmic reticulum. In stationary state 3T6 cells, it appears that there is no functional alternative pathway. We conclude that ICP34.5 exerts an effect on HSV maturation by controlling the passage of virus through infected cells. PMID- 7996166 TI - The cardiovascular effects of rate of verbal communication. AB - This study was designed to evaluate the effect of modifying rate of speech on the cardiovascular responses of type A and type B cardiac patients during verbalization. Blood pressure and heart rate were recorded in 111 cardiac patients every minute during two series: rapid and slow verbalization. Cardiovascular responses were significantly greater during rapid than during slow verbalization, independent of type A behavior pattern. This study demonstrates that reducing rate of speech can decrease cardiovascular reactivity during verbalization. PMID- 7996167 TI - Social support and cardiac recovery. AB - Social support has been implicated as a significant factor in recovery from myocardial infarction and coronary artery bypass surgery. Questions surrounding the role of social support in recovery that this article will answer include the following: How powerful is social support in promoting recovery? Must social support interventions be complex to be effective? What are the effects of problematic social support? How does social support promote recovery? How can nurses improve social support to maximize patient outcomes? PMID- 7996168 TI - Medical emergencies during cardiac rehabilitation: a naturalistic inquiry of the psychologic impact on peers. AB - The social support provided by other patients during cardiac rehabilitation is generally thought of as beneficial. Yet being with others also predisposes individual members to risk, being negatively affected if another group member should become acutely ill. When a patient witnesses a medical emergency of a peer in a cardiac rehabilitation setting, it is not known whether the event is perceived as helpful or harmful to the patient's psychologic recovery. This study describes an inductive analysis of patients' responses during 12 patient resuscitation events that occurred in the author's cardiac rehabilitation setting between 1989 and 1993, using naturalistic inquiry as a methodologic approach. PMID- 7996169 TI - The power to shape memories: critical care nurses and family visiting. AB - Through visiting policies, nurses have the power to control important memories that the patient and family experience during the patient's stay in the critical care unit. This Grand Rounds reviews the literature on critical care visitation and discusses five of the common reasons given for restricted visiting policies. A case study is used to illustrate the problems with restricted visitation. PMID- 7996170 TI - Investigating cardiovascular responses during social interactions. AB - Measurements on cardiovascular parameters can be obtained conveniently with a number of contemporary biomedical monitors and instruments. The researcher seeks to analyze and interpret these measurements in the context of cardiovascular responses to social interactions so that social interactions can be adjusted to support the recovery of the cardiovascular patient. In contrast to large group, intersubject designs that rely on group averages, the author encourages the researcher to explore single-subject, or "small N," experimental designs to provide an intrasubject investigation based on repeated measures before, during, and after social interactions. Statistical control charts may provide an operational definition for special cause variation that the researcher wishes to detect. Some control chart precautions are addressed, especially as regard autocorrelated data. References are provided to assist the researcher in the design and exploratory use of the basic charts and modifications thereof. PMID- 7996171 TI - The relationship of marital quality and psychosocial adjustment to heart disease. AB - Psychosocial adjustment to heart disease is variable. Some patients recover from a myocardial infarction or cardiac surgery quickly, return to work and leisure activities, and experience little emotional distress. Others suffer significant problems in psychosocial adaptation. We proposed and tested a theoretical model of adjustment that included the quality of the marital relationship, dysphoria, chronologic age, and time from the cardiac event (myocardial infarction or surgery) to identify the role that these variables play in adjustment. The study was conducted in 198 men diagnosed with coronary heart disease using the following instruments: the Spanier Dyadic Adjustment Scale, the Multiple Affect Adjective Checklist, and the Psychosocial Adjustment to Illness Scale. Data were collected on entry into the study and 3 months later to identify the stability of the relationships over time. The theoretical model was supported. Findings demonstrated that positive psychosocial adjustment to illness is influenced both by the quality of the patient's marriage and dysphoria. The spouse appears to influence psychosocial adjustment in an indirect manner by influencing the patient's experience of emotional distress or dysphoria. Nurses can enhance psychosocial adjustment to coronary heart disease by helping patients and spouses focus on ways to improve the quality of their marriage and by suggesting strategies to improve marital communication and decrease fear and misconceptions related to the illness. PMID- 7996172 TI - On the directional firing properties of hippocampal place cells. AB - Using a two-spot tracking system that allowed measurements of the direction of a rat's head in the environment as well as the position of the rat's head, we investigated whether hippocampal place cells show true direction-specific as well as location-specific firing. Significant modulations of firing rate by head direction were seen for most cells while rats chased food pellets in a cylindrical apparatus. It was possible, however, to account quantitatively for directional modulation with a simple scheme that we refer to as the "distributive hypothesis." This hypothesis assumes that firing is ideally location specific, and that all directional firing modulations are due to differences in the time that the rat spends in different portions of the firing field of the place cell in different head direction sectors. When the distributive hypothesis is put into numeric form, the directional firing profiles that it predicts are extremely similar to the observed directional firing profiles, strongly suggesting that there is no intrinsic directional specificity of place cell firing in the cylinder. Additional recordings made while rats ran on an eight-arm maze reveal that many firing fields on the arms are polarized; the cell discharges more rapidly when the rat runs in one direction than the other on the maze. This result provides an independent confirmation of the findings of McNaughton et al. (1983). For fields that appear to be polarized by inspecting firing rate maps of the raw data, the magnitude of directional firing variations is greater than predicted by the distributive hypothesis. By comparison with postsubicular head direction cells, it is shown that the distributive prediction of weaker-than observed directional firing is expected if there is a true directional firing component. A major conclusion reached from recording in both environments is that the directional firing properties of hippocampal place cells are variable and not fixed; this is true of individual units as well as of the population. PMID- 7996173 TI - Differential effects of morphine on noxious stimulus-evoked fos-like immunoreactivity in subpopulations of spinoparabrachial neurons. AB - In previous studies we reported that although morphine dose dependently inhibits noxious stimulus-evoked expression of the c-fos proto-oncogene in the rat spinal cord, morphine was without effect in certain populations of presumed nociresponsive neurons, even under conditions of complete behavioral analgesia. To determine whether the neurons that continue to express the c-fos gene include projection neurons, we evaluated the effect of morphine on noxious stimulus evoked c-fos expression in spinoparabrachial neurons retrogradely labeled with Fluoro-gold. In the formalin test, we found that morphine analgesia was associated with a significant reduction in the number of Fos-like-immunoreactive spinoparabrachial projection neurons in the lateral reticulated area of the neck of the dorsal horn. Morphine, however, did not reduce the number of Fos-like immunoreactive spinoparabrachial projection neurons either in the superficial dorsal horn or in the area around the central canal. These results indicate that under conditions of morphine analgesia two distinct populations of spinoparabrachial neurons can be recognized on the basis of their expression of the c-fos gene in response to noxious stimulation. Since the expression of the c fos gene has been correlated with neuronal activity, these data suggest that activity, and central transmission of nociceptive information, persists in certain nociresponsive projection neurons during morphine analgesia. Alternatively, if activity has, in fact, been blocked in these neurons, our results indicate that injury can produce significant molecular changes in neurons even though the neuronal activity and pain associated with the injury is blocked by morphine. PMID- 7996174 TI - Opioids modulate stress-induced proenkephalin gene expression in the hypothalamus of transgenic mice: a model of endogenous opioid gene regulation by exogenous opioids. AB - Stressful stimuli strongly induce proenkephalin gene expression within the paraventricular nucleus (PVN) of the hypothalamus. A human proenkephalin-beta galactosidase fusion gene has previously been shown to give correct phenotypic expression and appropriate stress regulation within the hypothalamus of transgenic mice; this model provides high sensitivity, cellular resolution, and ready quantification of levels of proenkephalin gene expression. Here we describe use of this transgenic model to study modulation of stress-regulated gene expression in the PVN by opiates. Acute or subacute morphine administration prior to a hypertonic saline stress produced marked superinduction of transgene expression compared with hypertonic saline stress alone. In contrast, chronic morphine administration decreased basal expression of the transgene, and inhibited stress-induced expression of the transgene. The endogenous proenkephalin mRNA was induced in parallel with the transgene as demonstrated by in situ hybridization; the immediate-early gene c-fos was also regulated in parallel with the transgene. These data suggest that acute or subacute morphine administration sensitizes proenkephalin neurons within the PVN and other regions of the hypothalamus to stress and that chronic morphine administration desensitizes this response. Because the molecular mechanisms regulating the expression of the transgene are well understood, this model provides a useful tool for investigating cellular and molecular effects of opioids on the hypothalamus. PMID- 7996175 TI - Hepatocyte growth factor is a mitogen for Schwann cells and is present in neurofibromas. AB - To characterize mitogens that might contribute to Schwann cell proliferation during development or in tumors, we tested the ability of hepatocyte growth factor (HGF) to stimulate Schwann cell division in vitro. HGF is a potent mitogen for purified rat Schwann cells; DNA synthesis in rat Schwann cells was stimulated 20-40-fold by 3-10 ng/ml HGF. Rat Schwann cells express c-met mRNA, encoding the HGF receptor, but not HGF mRNA, implying that HGF might act as a paracrine Schwann cell growth factor. HGF-stimulated Schwann cell proliferation differs from that of previously described Schwann cell mitogens in that its activity is abolished by forskolin and is not inhibited or potentiated by addition of transforming growth factor beta (TGF beta) or fibroblast growth factor (FGF). HGF is probably not a component of the axonal signal thought to cause Schwann cell division during development, as anti-HGF neutralizing antibodies failed to block neuron-stimulated Schwann cell proliferation. In contrast, mitogenic activity present in normal human adult nerves and in neurofibromas from patients with type 1 neurofibromatosis analyzed in the absence of forskolin is largely inhibitable by anti-HGF. Thus, HGF is a novel mitogen for Schwann cells in vitro and it is present in Schwann cell tumors, suggesting a potential role for HGF after wounding of peripheral nerves or in tumor growth. PMID- 7996176 TI - Functional mapping of horizontal connections in developing ferret visual cortex: experiments and modeling. AB - In cat striate cortex, patchy horizontal axonal projections link columns of similar orientation specificity. To assess the physiological correlates of such clustered projections, a new multisite stimulation technique was used to functionally map the pattern of horizontal synaptic inputs onto single layer 2/3 cells within tangential slices of developing ferret visual cortex. Twenty-four separate sets of horizontal fibers were stimulated within a 1200 microns strip of cortex, while evoked synaptic responses were recorded using whole-cell patch methods. For most cells, input maps demonstrated the presence of clustered horizontal connections in which multiple strong and weak synaptic responses were alternately evoked across the stimulated cortical region. Recordings from up to nine cells in a single slice revealed that patterns of synaptic input were closely correlated for cells in close proximity, and that this correlation decreased with distance, with no correlation at distances greater than 500 microns. To determine whether these physiological results were consistent with the known anatomical linkage of iso-orientation columns by clustered horizontal connections, mathematical analysis and computer simulations were performed upon orientation tuning maps obtained from optical imaging of activity-dependent intrinsic signals in mature ferret visual cortex. Optical imaging revealed an organization of iso-orientation domains consisting of broad regions of cortex across which orientation preference smoothly varied, together with "orientation centers" around which orientation preference was arranged in a pinwheel manner. The distribution of synaptic connections between different cortical sites was simulated by a model of functionally linked iso- orientation columns. Simulated synaptic input maps, generated by the same stimulation and recording arrangements used in our experimental protocol, accurately reproduced the observed patterns of clustered inputs onto experimentally recorded cells. These results indicate that even at the time of eye opening, prior to extensive visual experience, most cells receive patterns of synaptic inputs consistent with a clustered organization of horizontal connections that functionally link iso-orientation columns. PMID- 7996177 TI - Immunocytochemical localization and biological activity of 3 beta-hydroxysteroid dehydrogenase in the central nervous system of the frog. AB - The enzyme 3 beta-hydroxysteroid dehydrogenase/delta 5-delta 4 isomerase (3 beta HSD) catalyzes biosynthesis of progesterone (P) and all precursors of glucocorticoids, mineralocorticoids, androgens, and estrogens. Despite the broad interest raised by neurosteroids, the cellular localization of 3 beta-HSD has never been investigated in the brain. We took advantage of the availability of an antiserum raised against human placental 3 beta-HSD to determine the distribution of 3 beta-HSD-immunoreactive structures in the brain of the frog Rana ridibunda by the indirect immunofluorescence technique. Three populations of 3 beta-HSD immunoreactive cell bodies were observed in the hypothalamus, namely, in the rostral region of the preoptic nucleus, the dorsal infundibular nucleus, and the dorsal part of the ventral infundibular nucleus. A dense network of 3 beta-HSD immunoreactive nerve fibers was visualized in the dorsal area of the diencephalon, that is, in the lateral neuropil, the corpus geniculatus lateralis, and the nucleus posterolateralis thalami. Reversed-phase HPLC analysis of frog hypothalamic extracts combined with RIA detection showed the presence of substantial amounts of immunoreactive steroids coeluting with P and 17 hydroxyprogesterone (17OH-P). The synthesis of delta 4-3-keto-steroids in the frog hypothalamus was investigated using the pulse-chase technique with 3H pregnenolone (3H-delta 5P) as a precursor. The formation of five tritiated metabolites of 3H-delta 5P was observed, one of which coeluted with 17OH-P. Conversion of 3H-delta 5P into this radioactive metabolite was significantly reduced by trilostane, a specific inhibitor of 3 beta-HSD. Immunodetection of newly synthesized steroids in HPLC fractions of hypothalamic extracts, using 17OH P antibodies, revealed the existence of an immunoreactive steroid that exhibited the same retention time as synthetic 17OH-P. The present study provides the first immunocytochemical mapping of 3 beta-HSD, a key enzyme of the steroid biosynthetic pathway, in the CNS of a vertebrate. The data also demonstrate for the first time biosynthesis of neurosteroids in the brain of a nonmammalian vertebrate. PMID- 7996178 TI - The T alpha 1 alpha-tubulin promoter specifies gene expression as a function of neuronal growth and regeneration in transgenic mice. AB - We have previously demonstrated that one member of the alpha-tubulin multigene family, termed T alpha 1 in rats, is regulated as a function of neuronal growth and regeneration. To elucidate the molecular mechanisms responsible for coupling gene expression to morphological differentiation, we have isolated the T alpha 1 gene, have fused 1.1 kb of the 5' flanking region to a nuclear lacZ reporter gene, and have generated transgenic mice. Analysis of these transgenic mice demonstrated that marker gene expression was specific to the CNS and PNS, with expression in vivo at embryonic day 13.5 being similar to expression of the endogenous gene. Moreover, the induction of transgene expression was correlated temporally with neuronal commitment in developing neural crest-derived peripheral neurons and in the developing retina. Immunocytochemical analysis of mixed primary embryonic brain cultures confirmed that transgene expression was specific to neurons, with the majority of neurons, but not astrocytes or oligodendrocytes, expressing beta-galactosidase. Transgene expression in vivo was maintained in developing neurons until early in postnatal life, subsequent to which its expression decreased coincident with neuronal maturation. The transgene was then reinduced in regenerating facial motoneurons following unilateral axotomy of the facial nerve. Thus, 1.1 kb of 5' flanking sequence from the T alpha 1 gene contains the sequence elements responsible for specifying gene expression to embryonic neurons and for subsequently regulating gene expression in both developing and mature neurons as a function of morphological growth. PMID- 7996179 TI - T-cadherin expression delineates specific regions of the developing motor axon hindlimb projection pathway. AB - T-cadherin is a unique member of the cadherin family anchored to the membrane by a glycosyl phosphatidylinositol moiety (Ranscht and Dours-Zimmermann, 1991). T cadherin's distribution in the developing motor axon pathway was mapped by immunocytochemistry in the chick lumbosacral region as spinal neurons project to and innervate hindlimb muscle. On growing motor axons, T-cadherin was expressed biphasically. Initially, uniform T-cadherin expression occurred on motor neurons as they projected between the spinal cord and the base of the hindlimb (stage 21 24), and then decreased as the axons sorted to form dorsal, ventral and muscle nerve trunks (stage 25-27). Later, as motor axons entered and formed terminal axon arbors and synapses in muscle (stages 28-36), expression reoccurred heterogeneously among motor neuron pools. Thus, T-cadherin may guide the growth and fasciculation of all motor neurons during early axon extension, but only affect particular populations during the later expression period. In the mesenchyme of the motor axon pathway, T-cadherin was restricted to regions avoided by growing axons: the posterior-half sclerotome before and during the projection of motor axons through the T-cadherin-negative anterior half, and the extrasynaptic surfaces of developing muscle. The temporal and spatial expression patterns of T-cadherin and neurite outgrowth-promoting N-cadherin were complementary both in nerve and muscle tissues. Thus, in the posterior sclerotome and in maturing muscle, T-cadherin may act as a negative regulator that works in concert with neurite growth-promoting molecules to guide motor axons to their peripheral targets. PMID- 7996180 TI - Comparison of spatial firing characteristics of units in dorsal and ventral hippocampus of the rat. AB - The septal and temporal poles of the hippocampus differ markedly in their anatomical and neurochemical organization. Although it is well established that the internal representation of space is a fundamental function of hippocampal neurons, most of what is known about spatial coding in the hippocampus of freely moving animals has come from recordings from the dorsal one-third (largely for technical convenience). The present study therefore compared the spatial selectivity of CA1 neurons in the dorsal and ventral hippocampi of rats during performance of a food reinforced, random search task in a square chamber containing simple visual landmarks. Neural activity was recorded in the dorsal and ventral hippocampi of opposite hemispheres in the same rats, in many cases simultaneously. As in dorsal hippocampus, ventral CA1 units could be classified as "complex spike" (pyramidal) cells or "theta" interneurons. Both dorsal and ventral theta cells fired at relatively high rates and with low spatial selectivity in the apparatus. Of the population of complex spike cells in the ventral hippocampus, a significantly smaller number had "place fields" than in the dorsal hippocampus, and the average spatial selectivity was of significantly lower resolution than that found among dorsal hippocampal complex spike cells. Thus, a septotemporal difference of spatial selectivity was found in the CA1 field of the rat hippocampus, complementing many other anatomical and neuropharmacological studies. A number of possible functional interpretations can be suggested from these results, including a computational advantage of representing space at different scales or a preeminence of essentially nonspatial information processing in the ventral hippocampus. PMID- 7996181 TI - Transparent motion perception as detection of unbalanced motion signals. I. Psychophysics. AB - Our visual system can solve the difficult problem of representing multiple motions in the same part of the visual space, the motion transparency problem. We investigated the conditions under which transparent motion perception occurs through psychophysical observations, using a series of visual displays composed of two simple patterns moving in opposite directions. We found that whenever a display has finely balanced opposing motion signals in all local regions, it is perceptually nontransparent. The displays that appeared transparent always contain locally unbalanced motion signals, with some local regions having net motion signals in one direction and some other regions in the opposite direction. These interdigitating net motion signals in both directions appear to be integrated separately to form two overlapping transparent surfaces. Displays that were spatially balanced could be made perceptually transparent if the two components moving in opposite directions were at different stereo depth planes or had different spatial frequency contents. Our results can be explained by proposing a disparity- and spatial frequency-specific suppression stage in the motion pathway, at which motion signals of different directions, but of the same disparity and spatial frequency contents, locally inhibit each other. Such a mechanism would suppress noise input to the motion system, which generally activates several direction channels simultaneously, and would still not eliminate activity evoked by transparent surfaces that are at different depths or have different textures. PMID- 7996182 TI - Transparent motion perception as detection of unbalanced motion signals. II. Physiology. AB - We investigated how the primate visual system solves the difficult problem of representing multiple motion vectors in the same part of the visual space--the problem of motion transparency. In the preceding companion article we reported that displays with locally well-balanced motion signals in opposite directions are perceptually nontransparent (i.e., one does not see two coherent moving surfaces) and that transparent displays always contain locally unbalanced motion signals. This is exemplified by our paired and unpaired dot patterns. Although both types of stimuli contain two sets of dots moving in opposite directions, the former is locally well balanced and appears like flicker while the latter gives a perception of two transparent surfaces. In this article we report our physiological recordings from areas V1 and MT of behaving monkeys, comparing single-cell responses to the paired and the unpaired dot patterns. Although a small proportion of directionally selective V1 cells responded differently to the two types of patterns, the average V1 responses could not reliably distinguish between the paired and the unpaired stimuli. A large fraction of MT cells, on the other hand, responded significantly better to the unpaired dot patterns than to the paired ones. Furthermore, the average response of all MT cells to the unpaired dot patterns was significantly higher than that to the paired dot patterns. These results demonstrate a neural correlate of the perceptual transparency at the level of MT. On the other hand, V1 cells do not generally discriminate between the transparent and nontransparent stimuli, indicating that V1 activity is not well correlated with the perception of motion transparency. Our results are consistent with a two-stage model for motion processing: the first stage measures local motion and the second stage introduces suppression if different directions of motion are present at a local region of the visual field. The first stage is located primarily in V1 and the second stage primarily in MT. Finally, we found a strong and negative correlation between the degree of the opponent-direction suppression of MT cells and their responses to flicker noise stimuli. This result suggests that one of the fundamental roles of the opponent direction suppression in MT is noise reduction. PMID- 7996183 TI - Transparent motion perception as detection of unbalanced motion signals. III. Modeling. AB - In the preceding two companion articles we studied the conditions under which transparent motion perception occurs through psychophysical experiments, and investigated the underlining neural mechanisms through physiological recordings. The main finding of our perceptual experiments was that whenever a display has finely balanced motion signals in all local areas, it is perceptually nontransparent, and that transparent displays always contain motion signals in different directions that are either spatially unbalanced, or unbalanced in their disparity or spatial frequency contents. In the physiological experiments, we found two stages in the processing of transparent stimuli. The first stage is located primarily in area V1. At this stage motion measurements are made and V1 cells respond well to both the balanced, nontransparent stimuli and the unbalanced, perceptually transparent stimuli. The second stage is located primarily in area MT. MT cells show strong suppression between opposite directions of motion. The suppression for the unbalanced, transparent stimuli is significantly less than that for the balanced, nontransparent stimuli. Therefore, the activity in the second, MT stage correlates better with the perception of motion transparency than the first, V1 stage, which does not distinguish reliably between transparent and nontransparent motion. The above experiments suggest a two-stage model of motion perception with a motion measurement stage in V1 and an opponent-direction suppression stage in area MT. In this article we explicitly test this model through analysis and computer simulations, and compare the response of the model to the perceptual and physiological results using the same balanced and unbalanced stimuli we used in the experiments. In the first stage of the computational model, motion energies in different spatial frequency and disparity ranges are extracted from each local region. Similar to V1, this stage does not distinguish between the balanced and unbalanced stimuli. In the subsequent stage motion energies of opposite directions but with same spatial frequency and disparity contents suppress each other using subtractive or divisive inhibition. This stage responds significantly better to the transparent stimuli than to the nontransparent ones, in agreement with MT activity. PMID- 7996184 TI - Bidirectional promoter of human monoamine oxidase A (MAO A) controlled by transcription factor Sp1. AB - The core promoter region of human monoamine oxidase (MAO) A has been identified in the two 90 bp repeat sequences, which can be further divided into four imperfect tandem repeats, each containing an Sp 1 binding site in the reversed orientation. Gel retardation and DNase 1 footprinting assays identified Sp 1 to be the major transcription factor binding to MAO A core promoter. In addition, positive association has been observed between cellular Sp1 concentration and MAO A promoter or catalytic activity, indicating that Sp1 is a controlling factor for human MAO A expression. DNA fragments from MAO A core promoter exhibit promoter activity in both orientations in a transient transfection assay, using human growth hormone as the reporter gene. A DNA probe isolated from upstream of the core promoter detected positive signals in a Northern analysis, suggesting that the reverse promoter activity may endogenously transcribe a new gene located upstream of MAO A. PMID- 7996185 TI - Model for the pharmacological basis of spontaneous synchronous activity in developing retinas. AB - Spontaneous waves of bursts of action potentials propagate across the ganglion cell surface of developing retinas. A recent biophysical model postulated that this propagation is mediated by an increase in extracellular K+, following its ejection from ganglion cells during action potentials. Moreover, the model hypothesized that bursts might terminate due to the accumulation of intracellular Ca2+ and the subsequent activation of a Ca(2+)-dependent K+ conductance in the cells' dendrites. Finally, the model proposed that an excitatory synaptic drive causes a neuromodulation of the waves' properties. To test the feasibility of the model, we performed computer simulations of the network of developing ganglion cells under control and pharmacological-manipulation conditions. In particular, we simulated the effects of neostigmine, Cs+ and TEA, low Ca2+ concentrations, and Co2+. A comparison of the simulations with electrophysiological and pharmacological experimental data recently obtained in turtles (Sernagor and Grzywacz, 1993a), and cats and ferrets (Meister et al., 1991; Wong et al., 1993), showed that the model for the most part is consistent with the behavior of developing retinas. Moreover, modifications of the model to allow for GABAergic inputs onto ganglion cells (Sernagor and Grzywacz, 1994) and poor [K+]out buffering (Connors et al., 1982) improved the model's fits. These results lent further support to important roles of extracellular K+ concentration and synaptic drive for the propagation of waves. PMID- 7996186 TI - Modulation of the axonal microtubule cytoskeleton by myelinating Schwann cells. AB - The Trembler PNS myelin-deficient mutant mouse offers a unique model for the study of axon-glial interactions. Previous work in our laboratory on Trembler mouse sciatic nerve established that myelinating Schwann cells exert a profound effect on the underlying neuronal cytoskeleton. Demyelinated axon segments exhibited decreases in the rate of slow axonal transport, axonal caliber, and neurofilament phosphorylation, as well as increases in neurofilament density. The present study considers effects on the microtubule cytoskeleton. At least two aspects of the microtubule cytoskeleton in Trembler PNS axons were altered by demyelination. First, the stability of the Trembler axonal microtubule cytoskeleton is decreased, as measured by decreased levels of insoluble tubulin (Sahenk and Brady, 1987). Second, the composition and phosphorylation of axonal microtubule-associated proteins, including tau, MAP 1A, and MAP 1B, are changed in Trembler demyelinated nerves. Further, the fraction of axonal tubulin moving at slow component b rates was increased (de Waegh and Brady 1990, 1991). These results provide further evidence that cell-cell interactions between myelinating glia and their underlying axons extend beyond a structural role, actively influencing biochemical and physiological properties of the axon. PMID- 7996187 TI - Ocular dominance column development: strabismus changes the spacing of adjacent columns in cat visual cortex. AB - To investigate the role of visual experience for the gross layout of ocular dominance (OD) columns in the visual cortex, I compared the respective patterns in normally raised and strabismic cats. OD domains were visualized by (1) transneuronal labeling of the afferents from the left or right eye with intraocular 3H-proline injections or (2) 14C-2-deoxyglucose autoradiography after monocular visual stimulation in awake animals. To obtain the complete pattern of OD columns, flat-mount sections were prepared from the unfolded cortical hemispheres. Eliminating correlated activity between the two eyes by making the animals strabismic influenced the gross layout of the OD domains. In area 17, OD domains become more sharply delineated than in normal animals and spaced more widely. Spatial frequency analyses revealed a mean spacing of adjacent columns of 1100-1300 microns in strabismic and of 800-1000 microns in normal cats. In area 18, the spacing of the ocular dominance domains is larger than in area 17 for both normal and strabismic cats (1500-1650 microns), but little influenced by strabismus. These results indicate that in area 17 decreased correlation of activity between the eyes alters the periodicity of OD columns. In addition, these observations suggest that not only the segregation of afferents into distinct columns but also the final expression of the columnar grid is influenced by visual experience, and in particular by the temporal patterning of neural activity. This is further evidence for the hypothesis that the development of OD columns is governed by activity-dependent self-organizing principles. PMID- 7996189 TI - Task-dependent effects of intra-amygdala morphine injections: attenuation by intra-amygdala glucose injections. AB - Intraseptal injections of morphine impair learning and memory in rats, and these impairments are reversed by intraseptal injections of glucose. With evidence that injections of morphine into the amygdala also impair memory for some tasks, the present experiment determined whether (1) intra-amygdala morphine injections impair performance in inhibitory avoidance and spontaneous alternation tasks, and (2) intra-amygdala glucose injections attenuate the effects of intra-amygdala morphine injections. Rats receiving bilateral injections of morphine (4.0 nmol) into the amygdala, 30 min prior to training in inhibitory avoidance, had retention latencies significantly lower than those of unoperated and CSF controls when tested 24 hr later. Bilateral morphine injections (4.0 or 8.0 nmol) 30 min prior to testing in a spontaneous alternation task did not alter performance. The morphine-induced impairment observed in inhibitory avoidance was not due to diffusion up the cannulas, altered sensitivity to shock, or seizure activity. A glucose dose of 16.67 nmol, but not 8.33 nmol, injected into the amygdala attenuated the morphine-induced deficit in inhibitory avoidance. Rats receiving CSF into the amygdala exhibited decreased retention latencies in inhibitory avoidance compared to those of unoperated controls. This decrease was not attenuated by glucose at doses of 8.33 and 16.67 nmol. Therefore, these findings suggest that the amygdala is another brain region in which glucose affects brain functions, possibly by interacting with the opioid system and/or other neurotransmitter systems. PMID- 7996188 TI - Age-related decrease of GABAA receptor subunits and glutamic acid decarboxylase in the rat inferior colliculus. AB - A selective age-related decrease in both the protein and mRNA levels of the most abundant GABAA receptor subunits has been revealed in the rat inferior colliculus. The number (not affinity) of the native and fully assembled GABAA receptors assayed by 3H-muscimol binding was also decreased (35-49%). The decrease in GABA receptors was accompanied by a decrease in the protein and mRNA of the GABA-synthesizing enzyme glutamic acid decarboxylase. No other region of the rat brain showed such large age-related changes in these GABAergic synaptic molecules. Specific antibodies and riboprobes in conjunction with a computerized image analysis system were used to quantify immunocytochemistry and in situ hybridization. In old Sprague-Dawley rats, the combination of beta 2 and beta 3 peptide subunits was reduced 55%, while the beta 2 and beta 3 mRNAs were decreased 31% and 22%, respectively. The gamma 2S and gamma 2L subunit proteins decreased 43% and 21%, respectively, while the gamma 2 mRNA, including both short and long forms, was reduced 61%. The alpha 1 subunit protein was decreased 28%, whereas the alpha 1 mRNA decreased 40%. The glutamic acid decarboxylase protein was reduced 62% while GAD65 mRNA decreased 42%. Similar age-related changes were also observed in the inferior colliculus of Fischer-344 rats. In contrast, no changes were observed in the level of expression of some glial and/or neuronal proteins such as S-100, glial fibrillary acidic protein, and 160 KDa neurofilament protein in the inferior colliculus.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7996190 TI - Postnatal development of the tyrosine hydroxylase-containing cell population within the rat locus coeruleus: topological organization andphenotypic plasticity. AB - The cellular phenotypic characteristics of tyrosine hydroxylase (TH) expression have been studied within the rat locus coeruleus (LC) during postnatal development at six different stages: postnatal day 4 (PND4), PND10, PND14, PND21, PND30, and PND42. Coronal brain sections were selected at intervals of 80 microns along the caudorostral extent of the LC and processed for TH immunohistochemistry. At each anatomical level we (1) reconstructed the mean space of the LC delineated by the TH positive cell bodies, (2) enumerated the mean number of these cell bodies, and (3) determined the mean volume circumscribed by these cell bodies and their density. The topological study revealed a steady remodeling of the structure until the third week, with a progressive reducing of a ventral cellular group in the anterior LC, which was no longer observable at PND21, concomitant to the stretch of the structure toward its caudal limit. We have noted invariant and variant cellular phenotypic characteristics of TH expression. At any stage, the LC could be separated into a posterior and an anterior subregion and its total volume remained quite stable during the studied period. At PND14 and PND21, we observed a transient 33% increase in the total number of TH positive perikarya as compared to PND42. Conjoint analysis of the topological reconstruction and the density of TH positive cells suggested there were three distinct and precisely localized subsets of "quiescent" neurons. TH gene expression in these cells would have lowered between PND14 and PND21 inside two subsets and between PND21 and PND30 inside the last one. So topologically defined populations of cells could be involved in specific functions. If they have not definitively lost their TH expression capacity, they could contribute to increasing TH levels in LC occurring in response to physiological perturbations or pharmacological treatments. PMID- 7996191 TI - Quantitative study of tyrosine hydroxylase protein levels within the somatic area of the rat locus coeruleus during postnatal development. AB - To date only global dosages of tyrosine hydroxylase (TH) protein have been realized in the locus coeruleus (LC) without discriminating the enzyme contained in the cell body area from the one in the surrounding neuropil. The preceding immunohistochemical study (Bezin et al., 1994) revealed a dramatic plasticity of the cellular expression of TH in the LC during the postnatal development of the rat. It was therefore necessary to develop a quantitative biochemical approach, strengthened by a great anatomical resolution, to follow the developmental evolution of TH levels exactly in the space containing the coerulean TH immunoreactive perikarya. In the present work two biochemical parameters necessary for precisely defining the phenotypic characterization of TH expression within the rat LC have been established during the postnatal development at six different stages: postnatal day 4 (PND4), PND10, PND14, PND21, PND30, and PND42. TH tissue concentration and content were precisely determined along the caudorostral extent of the LC within the previously (Bezin et al., 1994) defined spaces delimited by the TH-containing perikarya. TH tissue concentration remained quite stable during the postnatal development. TH quantity exhibited few age related variations with a transient peak at PND10 and followed the same evolution as the volume containing the TH-expressing perikarya. The mean cell contribution to the total quantity of TH measured in the whole LC showed important age-related fluctuations with a dramatic peak at PND10 followed by a drastic decrease until PND21.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7996192 TI - Disruption of microfilaments in growth cones following depolarization and calcium influx. AB - Depolarization of leech neurons growing on extracellular matrix extract (ECM) leads to cessation of neurite outgrowth, rounding up of the peripheral regions of the growth cone, loss of filopodia, and neurite retraction. These responses depend on the influx of calcium (Neely, 1993). The aim of the present experiments was to analyze how the cytoskeleton becomes reorganized as growth cones change their morphology. Immunocytochemistry revealed a loss of microfilaments in the tips of neurites growing on ECM after depolarization. Leech neurons cultured on a different substrate, the plant lectin concanavalin A (ConA), continue to grow during and after depolarization (Grumbacher-Reinert and Nicholls, 1992; Neely, 1993). As expected, we did not observe any change in the distribution of microfilaments after depolarization on ConA. Since there is evidence that this lack of response is due to a reduced calcium influx during depolarization of neurons on ConA (Ross et al., 1988), the effect of the calcium ionophore A23187 on the outgrowth of these cells was analyzed. In the absence of depolarization, this ionophore caused cessation of growth cone motility and a loss of microfilaments, while microtubules were not affected. Cytochalasin D, a microfilament-disrupting agent, induced changes in growth cone morphology and neurite retraction similar to those observed after depolarization and calcium influx. Application of phalloidin, a drug that stabilizes microfilaments, inhibited depolarization-induced retraction of neurites on ECM. By contrast, stabilization of microtubules with taxol did not prevent depolarization from inducing changes in growth cone morphology and neurite growth. These experiments show that changes in growth cone morphology and motility of leech neurons induced by depolarization and calcium influx are accompanied by a dramatic change in the organization of microfilaments, but not microtubules. PMID- 7996193 TI - The computation of position sense from spindles in mono- and multiarticular muscles. AB - It is known that muscle spindles provide the majority of information about limb position, but little is known about how position sense is computed from their signals. We have developed a family of musculoskeletal models in order to determine some of the fundamental properties associated with transforming noisy spindle information into putative internal coordinate frames for position sense. A two-joint model was developed containing one biarticular and two monoarticular muscles with a total of 1000 sensors distributed among them. The sensors were assumed to function like spindle secondary afferents under fusimotor control designed to optimize their ability to encode static position in the presence of constant output noise. The optimal distribution of sensors was found to depend strongly on the coordinate frame in which position was measured (intersegmental angle, segment orientation, or end-point of the limb) and on the topology of the biarticular muscle with respect to the plane of motion. A similar analysis was performed for an anthropometric model of the human arm, using previously published counts of muscle spindles. In general, the actual distribution of spindles about the elbow and shoulder does not seem to favor any single coordinate frame for position sense. We also looked at the potential accuracy in detecting changes in joint angles based on the distribution of muscle spindles throughout the human body. The distribution of spindles about individual joints accounts well for psychophysical data showing a proximodistal descending gradient of angular resolution that partially reflects the relative importance of more proximal joints for determining the location of the end-point. PMID- 7996194 TI - Neuronal and non-neuronal aromatase in primary cultures of developing zebra finch telencephalon. AB - Estrogenic metabolites of circulating androgens have important effects on the organization and activation of neural circuits controlling reproductive behavior and physiology in males of many vertebrate species. Previous studies indicate that aromatase, the enzyme that converts androgens to estrogens, is expressed most abundantly in neurons in limbic brain regions. Songbirds are unique in that aromatase is expressed at unusually high levels throughout the telencephalon of both males and females. We assume that estrogens formed in the telencephalon itself masculinize neural circuits controlling song, since the brain is a major source of circulating estrogens in adult males. However, the cellular localization of telencephalic aromatase in songbirds remains unknown. We have established primary cultures from telencephalons of developing zebra finches and found aromatase activity (conversion of 3H-androstenedione or 3H-testosterone to 3H-estrone plus 3H-estradiol) at some of the highest levels reported for brain tissue of any species. Both neurons and glia were identified in these cultures based on cell morphology and labeling by specific immunohistochemical markers. However, when culture conditions were manipulated to reduce the incidence of either neurons or glia by varying the age of cultures or their plating density, treating with the neurotoxin kainic acid, physically shaking off loosely attached neurons, or preparing cultures in media that encouraged enrichment of neurons, high levels of aromatase persisted. Furthermore, Northern blot analysis of total RNA extracted from enriched neuronal or glial cultures indicated the presence of aromatase mRNA in both cell preparations. In situ hybridization with a zebra finch aromatase cDNA probe conjugated to digoxigenin showed the cultures contained darkly labeled neurons and lightly labeled non-neuronal cells, presumably astrocytes. We conclude that aromatase is expressed in both neuronal and non-neuronal cells in these cultures, suggesting that both cell types may also express the enzyme in vivo. The presence of aromatase outside of neurons suggests that glia may be targets of estrogen action or that glia may supply some estrogen to the estrogen-sensitive neural circuits in this species. PMID- 7996195 TI - Long-term delayed vascularization of human neural transplants to the rat brain. AB - Human neural transplants are being developed to treat Parkinson's disease. Previous characterization of human transplants focused on neuronal development, while little is known of the interaction between the transplant and its environment, among which blood is of prime importance. We evaluated here the formation of blood vessels in human neural xenografts placed into the brain of rats immunosuppressed with cyclosporin A. Using capillary wall markers, we found that human transplants remain virtually nonvascularized for more than 1 month. Angiogenesis takes place very slowly and the density of blood vessels is still quite poor after 3 months, the fine structure of these capillaries, when they form, is apparently normal. Functional studies indicate that the vascular network formed in the transplant allows blood circulation and exhibits a working barrier to macromolecules. Glucose uptake and consumption and cytochrome oxidase activity are almost undetectable up to 3 months after grafting. These results demonstrate that vascularization is much delayed in human xenografts into the rat brain. This delay is likely to be dependent on the maturation of the transplanted tissue. A dedifferentiation of human endothelial cells cotransplanted with neural cells occurs since histochemical and immunocytochemical markers revealing endothelial cells in the human fetus are not present up to 1 month in the transplant. The origin of this phenomenon is a matter of speculation. How neural cells survive and mature in such conditions are issues of prime interest for the future of human neural grafting. PMID- 7996196 TI - ATP mediates fast synaptic potentials in enteric neurons. AB - Conventional intracellular electrophysiological methods were used to study fast synaptic transmission in the myenteric plexus of guinea pig ileum in vitro. Fast excitatory postsynaptic potentials (fEPSPs) were evoked in 98 neurons following single stimuli applied to interganglionic connectives. The nicotinic antagonist hexamethonium (100 microM) reduced fEPSPs by 83% in 37 neurons; these fEPSPs were considered to be cholinergic. In 61 neurons, hexamethonium reduced fEPSPs by 33%; fEPSPs recorded in the presence of hexamethonium were considered to be noncholinergic. Similar data were obtained using the nicotinic antagonist mecamylamine (10 microM) to block fEPSPs. Hexamethonium or mecamylamine completely blocked depolarizations caused by acetylcholine (ACh) applied by ionophoresis. The P2 receptor antagonist suramin (1-300 microM) inhibited noncholinergic fEPSPs in 30 cells; the suramin IC50 was 4 microM. Suramin (100 microM) did not block depolarizations caused by ACh or 5-HT, but suramin blocked depolarizations caused by ATP. Hexamethonium did not block ATP-induced depolarizations. The estimated reversal potential for suramin-sensitive fEPSPs and ATP-induced depolarizations was -25 and -16 mV, respectively. ATP responses were reduced in low-sodium (26 mM) extracellular solution, suggesting that ATP activates a cation channel. These data indicate that in myenteric nerves ATP, in addition to ACh, contributes to fast synaptic transmission. PMID- 7996197 TI - Optical mapping of early embryonic expressions of Mg(2+)-/APV-sensitive components of vagal glutaminergic EPSPs in the chick brainstem. AB - Multiple-site optical recording of transmembrane voltage activity, using a voltage-sensitive dye (NK2761) and a 12 x 12 element photodiode array, was employed to monitor neural responses in the slice preparations that were dissected from 6-9-d-old embryonic brainstems. Transmembrane voltage-related optical responses evoked by a brief square current pulse applied with a microsuction electrode to the vagus nerve were recorded simultaneously from many sites in the preparation. In preparations from 6-d-old embryos, only action potential-related spike-like optical signals were often detected in the normal bathing solution containing 0.5 mM Mg2+. However, in several loci of some preparations, excitatory postsynaptic potential-related slow signals were elicited in a Mg(2+)-free bathing medium, and these elicited slow signals were blocked by DL-2-amino-5-phosphonovaleric acid (2-APV). These results show a possible embryonic expression of NMDA receptor-mediated excitatory postsynaptic potentials. The slow signals were usually detected from tested preparations from 7-9-d-old embryos in normal bathing solution. The later phase of the slow signals was enhanced in a Mg(2+)-free bathing medium, and the enhanced component was also sensitive to 2-APV and insensitive to 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX). There were regional differences in the degree of the enhancement of the slow signals in the Mg(2+)-free bathing medium, and of the 2-APV-induced reduction of the slow signals. We have constructed early developmental maps of the spatial patterns of the slow signals related to Mg(2+)- and 2-APV-sensitive postsynaptic potentials. These maps reflect the spatial distribution of functional expression of the NMDA receptors during early development of the chick brainstem. The present findings are new data that have not been reported previously, and they have been obtained for the first time using the multiple site optical recording technique with a voltage-sensitive dye. PMID- 7996198 TI - Effect of serotonin depletion on vibrissa-related patterns of thalamic afferents in the rat's somatosensory cortex. AB - To investigate the role of 5-HT in the development of the somatosensory cortex, this amine was depleted in newborn (P-0) rats with a single subcutaneous injection of the toxin 5,7-dihydroxytryptamine (5,7-DHT) and thalamocortical organization was assayed by application of the carbocyanine dye Di-I to the thalamocortical radiations or ventrobasal thalamus, or by staining cortical sections for AChE or cytochrome oxidase (CO). High-performance liquid chromatographic analysis of cortices from animals killed on P-6 or P > 60 demonstrated that 5,7-DHT treatment resulted in 85.04 +/- 12.6% and 72.5 +/- 1.5% reductions in cortical 5-HT, respectively. Alternate cortices from the brains of animals killed on P-6 processed for 5-HT immunoreactivity demonstrated a complete absence of the vibrissa-related pattern of immunoreactivity and only a small number of coarse immunoreactive axons. The 85% depletion of 5-HT did not alter the somatotopic organization of thalamocortical afferents in animals killed on P 6 or P > 60, but it did cause 30.5 +/- 7.3% and 19.1 +/- 3.7% reductions in the cross-sectional areas of the patches of thalamocortical afferents corresponding to the long mystacial vibrissae (p < 0.05). These reductions were not associated with significant reductions in either brain or cortical weight or with decreases in the dimensions of the thalamic representation of the vibrissa follicles. These results indicate that 5-HT plays a significant role in the development of the thalamic innervation of the primary somatosensory cortex. PMID- 7996199 TI - Opioid receptors modulate diverse types of calcium channels in the nucleus tractus solitarius of the rat. AB - We have investigated the coupling between opioid receptors and different types of Ca2+ channels in neurons acutely isolated from the nucleus tractus solitarius (NTS) of the rat. Using fura-2-based imaging we found that Ca2+ transients evoked by depolarization with 50 mM KCl were suppressed by the mu-opioid receptor agonist D-Ala2,N-MePhe4,Gly5-ol-enkephalin (DAMGO) and less effectively by the kappa-receptor agonist U-69,593. The delta-receptor agonist D-Pen2,D-Pen5 enkephalin (DPDPE) was ineffective. In whole-cell voltage-clamp recordings from these neurons, depolarizing voltage steps elicited high-threshold Ca2+ currents that could be distinguished pharmacologically into different components. Part of the current could be blocked by dihydropyridines, part by omega-conotoxin-GVIA and part by omega-agatoxin-IVA. This suggests that the neurons contained L-, N-, and P/Q-type Ca2+ channels. DAMGO and U-69,593 both blocked part of the Ca2+ current but DPDPE was ineffective. Perfusion of GTP-gamma-S into the cells produced a rapid rundown of the Ca2+ current and occluded further effects of the opioid agonists, suggesting the involvement of a G-protein in the coupling mechanism. Inhibition of L-channels did not alter the effect of DAMGO. On the other hand inhibition of N-channels occluded about 80% of the effect of DAMGO. Inhibition of the P/Q-current occluded the remainder of the DAMGO effect. Thus, it appears that activation of opioid receptors can inhibit N- and P/Q-type Ca2+ channels but not L-channels in these cells. It is likely that such effects are important in opioid-mediated inhibition of transmitter release in the brain. PMID- 7996200 TI - Inhibition of neurite growth by the NG2 chondroitin sulfate proteoglycan. AB - The chondroitin sulfate proteoglycans (CSPGs) have been implicated as both positive and negative modulators of axonal growth; however, the functional properties of only a few specific CSPGs have been investigated. Here we demonstrate that NG2, an integral membrane CSPG expressed on the surfaces of glial progenitor cells, inhibits neurite growth from neonatal rat cerebellar granule neurons when presented to the cells as a component of the substrate. Growth inhibition occurred when NG2 was mixed with either laminin or L1, two potent promoters of axonal extension. Moreover, when given a choice between surfaces coated with NG2 and laminin or L1, the axons of the cerebellar neurons extended preferentially on laminin or L1 and avoided areas of the substrate containing NG2. The NG2 proteoglycan inhibited neurite growth after digestion with chondroitinase ABC, demonstrating that the inhibitory activity is a property of the core protein and not the covalently attached chondroitin sulfate glycosaminoglycan chains. NG2 also inhibited neurite growth from embryonic rat dorsal root ganglia neurons on substrates containing laminin. However, when the sensory neurons were plated onto surfaces containing the L1 glycoprotein and NG2, neurite growth was not inhibited. These results demonstrate that the NG2 proteoglycan provides an unfavorable substrate for axonal growth. Cells that express this proteoglycan in vivo may participate in axonal guidance by defining areas of the developing CNS that are nonpermissive for axonal extension from specific classes of developing neurons. PMID- 7996201 TI - Cell death of spinal motoneurons in the chick embryo following deafferentation: rescue effects of tissue extracts, soluble proteins, and neurotrophic agents. AB - In the absence of descending spinal and supraspinal afferent inputs, neurons in the developing lumbar spinal cord of the chick embryo undergo regressive changes including cellular atrophy and degeneration between embryonic days 10 and 16. There are significant decreases in the number of motoneurons, interneurons, and sensory (dorsal root ganglion) neurons. Although there are several possible explanations for how afferents might regulate the maintenance of neuronal viability, we have focused attention on the putative role of neurotrophic agents in these events. Previous studies have shown that specific tissue extracts (e.g., muscle, brain), soluble proteins, growth factors, and trophic agents can promote the in vitro and in vivo survival of avian motoneurons during the period of natural cell death (embryonic days 6-10). Several of these agents were also effective following deafferentation. These included brain extract (BEX), muscle extract (MEX), conditioned medium from astrocyte cultures (ACM), as well as the following neurotrophic agents: nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), neurotrophin-3 (NT-3), S-100, insulin-like growth factor-I (IGF-I), ciliary neurotrophic factor (CNTF), platelet-derived growth factor (PDGF), basic fibroblast growth factor (bFGF), and leukemia inhibitory factor (CDF/LIF). Both transforming growth factor-beta (TGF-beta) and acidic fibroblast growth factor (aFGF) were ineffective. Although considerable more work is needed to determine which (and how) specific CNS-derived trophic agents regulate motoneuron survival, the present results are consistent with the notion that neurotrophic agents released from or modulated by synaptic inputs to target neurons promote neuronal differentiation and survival in the CNS. PMID- 7996202 TI - The cortical component of experience-dependent synaptic plasticity in the rat barrel cortex. AB - Rats were raised with altered tactile experience from P0 by removing all but one vibrissa (D1) from one side of the face (D1-spared animals). This procedure (univibrissa rearing) has previously been shown to cause neurons in cortical barrels surrounding D1 to develop greater than normal responses to D1 vibrissa stimulation and smaller than normal responses to principal vibrissa stimulation (Fox, 1992). In this study, it was found that the potentiated D1 responses could be attenuated by acute microlesions placed in the D1 barrel, while principal vibrissa responses were unchanged or even slightly elevated for the same cases. The ratio of the average D1 to principal vibrissa response was approximately proportional to the volume of tissue damaged in the D1 barrel. This result implies that the synaptic plasticity seen in cortex of D1-spared animals is due to synaptic changes that take place within the barrel cortex rather than to relay of changes occurring at a subcortical level. In addition, lesions aimed at the septum between D1 and an adjacent barrel almost completely abolished responses to D1 stimulation in that barrel, including short-latency responses (5-10 msec). Only neurons severed horizontally from D1 were affected. Neurons that maintained a connection with the D1 barrel via a bridge of septal tissue preserved their usual elevated levels of response to D1 stimulation and their aberrant short latency responses. This result implies that pathways radiating out from the D1 barrel/column, and connecting neurons in the D1 barrel to cells in surrounding barrels, undergo synaptic plasticity induced by univibrissa rearing. PMID- 7996203 TI - Estradiol regulates hippocampal dendritic spine density via an N-methyl-D aspartate receptor-dependent mechanism. AB - In the adult female rat, the densities of dendritic spines and synapses on hippocampal CA1 pyramidal cells are dependent upon the ovarian steroid estradiol; moreover, spine and synapse density fluctuate naturally as ovarian steroid levels vary across the estrous cycle. To determine whether the effects of estradiol on dendritic spine density require activation of specific neurotransmitter systems, we have treated animals concurrently with estradiol and one of four selective neurotransmitter receptor antagonists: MK 801, a noncompetitive NMDA receptor antagonist; CGP 43487, a competitive NMDA receptor antagonist; NBQX, an AMPA receptor antagonist; or scopolamine, a muscarinic receptor antagonist. Our results indicate that the effects of estradiol can be blocked by treatment with either of the NMDA receptor antagonists, but treatment with an AMPA or muscarinic receptor antagonist has no effect on spine density. Thus, we have concluded that estradiol exerts its effect on hippocampal dendritic spine density via a mechanism requiring activation specifically of NMDA receptors. PMID- 7996204 TI - Essential role of myosin light chain kinase in the mechanism for MgATP-dependent priming of exocytosis in adrenal chromaffin cells. AB - Ca(2+)-induced exocytosis in chromaffin cells now seems to consist of at least two distinct steps:MgATP-dependent Ca(2+)-dependent priming of the secretory apparatus, and Ca(2+)-dependent MgATP-independent step that triggers exocytosis (Bittner and Holz, 1992). Recently we found that a specific inhibitor of myosin light chain kinase (MLCK), wortmannin, inhibits Ca(2+)-induced catecholamine release from digitonin-permeabilized chromaffin cells, suggesting an implication of MLCK in the mechanisms of Ca(2+)-induced exocytosis (Imaizumi et al., 1992b). To elucidate further the implication of MLCK in the mechanism of exocytosis, we studied the effects of wortmannin and a peptide inhibitor (SM-1) corresponding to the pseudosubstrate domain of MLCK on MgATP-dependent and MgATP-independent release in digitonin-permeabilized chromaffin cells. Ca(2+)-induced exocytosis from the permeabilized cells in the presence of MgATP was inhibited by both SM-1 and wortmannin. Inhibitory effect of wortmannin on the rate of release induced by 10 microM Ca2+ in the presence of MgATP was much prominent in the later phase (1 10 min), although the initial rate was also decreased. SM-1 strongly inhibited ATP-dependent release without affecting Ca(2+)-dependent ATP-independent release at all. In addition, priming effect of MgATP that underlies Ca(2+)-dependent ATP independent release was remarkably reduced by both wortmannin and SM-1. These results suggest that MLCK plays an essential role in ATP-dependent priming of Ca(2+)-induced exocytosis in chromaffin cells. PMID- 7996205 TI - Neuropeptide induction of cyclic GMP increases in the insect CNS: resolution at the level of single identifiable neurons. AB - In insects, the neuropeptide eclosion hormone (EH) acts on the CNS to evoke the stereotyped behaviors that cause ecdysis, the shedding of the cuticle at the end of each molt. Concomitantly, EH induces an increase in cyclic GMP (cGMP). Using antibodies against this second messenger, we show that this increase is confined to a network of 50 peptidergic neurons distributed throughout the CNS. Increases appeared 30 min after EH treatment, spread rapidly throughout these neurons, and were extremely long lived. We show that this response is synaptically driven, and does not involve the soluble, nitric oxide (NO)-activated, guanylate cyclase. Stereotyped variations in the duration of the cGMP response among neurons suggest a role in coordinating responses having different latencies and durations. PMID- 7996206 TI - Facilitation of calcium-dependent potassium current. AB - The activation of Ca-dependent K+ current, Ic, was studied in macropatches on the cell bodies of molluscan neurons. When a depolarizing voltage-clamp pulse was applied repeatedly, Ic facilitated in a manner that resembled the facilitation of synaptic transmitter release. Facilitation was characterized by an increase in Ic amplitude, a progressive increase in instantaneous outward current, and a decrease in utilization time. Experiments were done to investigate the mechanism responsible for Ic facilitation. Facilitation was reduced by microinjection of an exogenous Ca2+ buffer into the cytoplasm, indicating that facilitation is a Ca(2+)-dependent process. It was also reduced at elevated temperatures. Conversely, facilitation was greatly potentiated by blocking the Na/Ca exchange mechanism. It is concluded that the facilitation of Ca-dependent K+ current results from the accumulation of Ca2+ at the inner face of the membrane during the repeated activation of Ca2+ channels by depolarization. The Ca2+ indicator fluo-3 was used in fluorescence imaging experiments to measure changes in [Ca]i near the cell membrane during repeated depolarizing pulses and the interpretation of these results was aided by numerical simulations of Ca2+ accumulation, diffusion, and buffering in the peripheral cytoplasm. These experiments showed that the time course of Ic facilitation matches the time course of Ca2+ accumulation at the membrane. It was found that the strength of Ic facilitation varies among patches on the same neuron, suggesting that the accumulation of Ca2+ is not uniform along the inner surface of the membrane and that gradients in [Ca]i develop and are maintained during trains of depolarizing pulses. Potential mechanisms that may lead to local differences in Ca2+ accumulation and Ic facilitation are discussed. PMID- 7996207 TI - Direct measurement of brain temperature during and after intraischemic hypothermia: correlation with behavioral, physiological, and histological endpoints. AB - The aim of the present study was to evaluate critically the protection afforded by hypothermia against ischemic injury to the hippocampus. Hypothermic treatment was applied selectively to the brain during a 5 min carotid artery occlusion in gerbils. Following a period of recovery, two independent measures were used to assess hippocampal function: (1) an open field test of spatial memory (assessment was made during the first 10 d after ischemia) and (2) measurement of evoked potentials from area CA1 in hippocampal slices (3 weeks after the ischemic episode). The functional outcome portrayed by these tests was compared to a morphological evaluation of CA1 pyramidal cells at three rostrocaudal levels. All evaluations were carried out in the same animals. We found converging evidence that intraischemic hypothermia provides virtually complete protection against a 5 min episode of cerebral ischemia. Animals treated with hypothermia performed as well as sham-operated controls in a spatial memory task, had field potentials that were indistinguishable from normal animals and CA1 cells appeared normal when assessed histologically. In contrast, ischemia at normothermia resulted in a deficit in open field behavior (p < 0.01), diminished field potentials in stratum radiatum (p < 0.01), and near total loss of pyramidal cells in dorsal CA1 (p < 0.01). There was a remarkably high correlation between these diverse measures (r ranged from 0.7 to 0.9, p < 0.01), which provides strong support for the use of hypothermia as an effective treatment for ischemia. This study introduces a novel approach for the evaluation of putative anti-ischemic treatments: combining behavioral, electrophysiological, and histological measures.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7996208 TI - A comparison of nucleus accumbens neuronal firing patterns during cocaine self administration and water reinforcement in rats. AB - The firing patterns of nucleus accumbens (NA) neurons in the rat were recorded during cocaine self-administration and responding for water. Recordings were obtained from permanently implanted multiple-electrode arrays (eight microwires) inserted bilaterally into rostral portions of the NA in subjects (n = 18) exhibiting stable cocaine self-administration (0.33 mg/infusion), and during stable responding for water reinforcement. Electronically isolated and identified NA neurons exhibited four distinct patterns of phasic activity relative to the reinforced response. Three of these firing patterns were observed during both cocaine self-administration and water reinforcement sessions. Response-related activity was categorized by cells that showed an anticipatory increase in firing rate during the preresponse phase (type PR), and by cells that were excited (type RFE) or inhibited (type RFI) following the response in the reinforcement phase. PR and RFE cells showed significantly reduced peak firing during cocaine self administration, compared to similar cells in water reinforcement sessions. A fourth type of NA firing pattern (type PR+RF) was observed only in cells recorded during cocaine self-administration sessions (Carelli et al., 1993b). PR+RF neurons exhibited two distinct peaks, one preceding the response and terminating at response completion (like PR cells), and a second peak immediately following the response (like RFE cells) with an inhibitory period between the two peaks (like RFI cells). The findings are discussed in terms of the role of the NA in mediating the reinforcing properties of both cocaine and water. PMID- 7996209 TI - Propofol modulates activation and desensitization of GABAA receptors in cultured murine hippocampal neurons. AB - Propofol (2,6 di-isopropylphenol) is an alkyphenol recently introduced for use as a general anesthetic. The modulation of GABAA receptor activation and desensitization by propofol was studied using a rapid perfusion system and whole cell voltage-clamp recordings from mouse hippocampal neurons. The effects of concentrations of propofol used clinically on single-channel and synaptic currents were also examined. Propofol evoked current responses (EC50 = 61 microM) and shifted the dose-response curve of GABA-activated current to the left without altering the maximum of the GABA response. Preincubation with propofol and GABA led to desensitization of the GABA response (EC50 = 454 microM and 23 microM, respectively). Saturating concentrations of GABA (600 microM) evoked currents that peaked and then declined in a biexponential fashion with fast and slow time constants of tau f = 1.0 sec and tau s = 3.5 sec. Propofol (10 microM) did not change the amplitude of the peak response but decreased the rates of decay approximately 1.5-fold and enhanced the steady-state current proportionately. Recovery from desensitization was also biexponential (tau f = 11 sec, tau s = 69 sec) but not influenced by propofol. Single-channel recordings from outside-out patches demonstrated that both propofol and GABA activated channels with a 30 pS and 21 pS open state. Propofol increased the frequency but not the duration or conductance of GABA-activated events. Miniature inhibitory postsynaptic currents (mlPSCs) were evoked by the application of hypertonic sucrose to the cell soma. Propofol (2 microM) prolonged the decay time of mlPSCs to an extent similar to which it increased the open probability of GABA-activated channels (2.3- vs 3 fold). A sequential model, based on a previous scheme of GABA receptor gating (Weiss and Magelby, 1989), is presented to summarize propofol's actions on GABAA receptor function. We show through simulation that the model reliably reproduced the whole-cell tracings. Our results indicate that propofol's neurodepressive actions will be associated with enhancement of inhibitory synaptic transmission. PMID- 7996210 TI - A call for leadership. PMID- 7996211 TI - Factors related to career retention among dental hygienists. AB - PURPOSE: The purpose of this research was to investigate the reasons dental hygienists consider leaving or leave dental hygiene and to determine if the reasons vary by employment category. METHODS: In March 1988, mail questionnaires designed by the author were sent to a nationwide sample of 1,008 dental hygienists who graduated in 1982 and who had been surveyed every six months beginning in their senior year of dental hygiene school. Consideration of leaving dental hygiene was ascertained with an open-ended question. Responses to this question were categorized into five determinants of work change: economic, psychological, sociological, physiological, and environmental. Chi-square analysis was used to ascertain if determinants of work change were associated with employment. RESULTS: Responses were received from 812 dental hygienists--an 81% response rate overall and an 83% response rate from subjects with valid addresses. While 82% of the respondents were employed in dental hygiene, 7% were employed outside of dental hygiene, and 12% were not employed. Of the respondents, 57% had considered leaving dental hygiene within six years after graduation. Reasons for considering leaving varied by employment status. Dental hygienists currently employed in dental hygiene stated a wide variety of reasons for considering leaving, but most important were psychological factors. Environmental (family responsibility) factors were most important for unemployed dental hygienists, while economic factors were most important for dental hygienists employed outside dental hygiene. CONCLUSIONS: Factors identified in this research can be used to help understand, and to design efforts to enhance, career retention. Additional research is needed to determine whether the causative factors for job turnover and career turnover are different or essentially the same. PMID- 7996212 TI - The effect of personal protective equipment on high-and low-dental fear patients. AB - PURPOSE: This investigation was designed to examine both high- and low-dental fear patients' perceptions about and anxiety responses to personal protective equipment (PPE) as presented in a videotaped, simulated interaction between oral healthcare worker and patient. METHODS: Sixty-two individuals representing a convenience sample presented at the University of Missouri-Kansas City (UMKC) Dental School and were screened for eligibility. The Dental Fears Survey was administered to participants to assess level of dental fear. Subjects were then matched according to fear level, gender, and age, and randomly assigned to an experimental or control group. Subjects viewed a videotaped vignette of a male dentist conducting a new patient interview. The control group viewed a tape in which the provider did not utilize PPE. The experimental group viewed the provider putting on PPE at completion of the interview. Subjects were instructed to complete a semantic differential scale at completion of the tape in order for the researchers to assess their attitude toward the scene. Paired adjectives in the semantic scale were scored from 1 to 7, with low scores reflecting negative evaluations and high scores reflecting positive evaluations. Heart rate and skin conductance were measured prior to and during the viewing of the videotapes by means of a photoplethysmograph and an electrodermograph, respectively. RESULTS: A two-factor ANOVA found the main effect of fear to be significant (p < .05), with subjects exhibiting high levels of dental fear rating both videotapes (PPE & NO PPE) more negatively than subjects exhibiting low levels of dental fear. A repeated measure ANOVA was used for analysis of heart rate and skin conductance. The Dunn's Multiple Means Comparison Test showed that skin conductance increased significantly (p < .05) in both groups from baseline to presentation of the oral healthcare environment. CONCLUSIONS: A videotaped presentation of the dental environment produced significantly more negative evaluations from patients with high fear than from patients with low fear. Both groups experienced a significant increase in skin conductance (perspiration) upon presentation of the oral healthcare environment. However, presence of PPE did not adversely affect patient perceptions of the oral healthcare provider. PMID- 7996213 TI - Oral statement of the American Dental Hygienists' Association presented to the Institute of Medicine's Committee on the Future of Dental Education January 9, 1994. PMID- 7996214 TI - Preventive oral health behaviors among Detroit-area residents. AB - PURPOSE: It has been recommended that adults brush and floss their teeth daily and have periodic oral health checkups. A study was conducted to determine if those recommendations are followed. METHODS: Data were collected during face-to face interviews with a probability sample of 662 dentate adults residing in the Detroit metropolitan area from August to November 1989. Participants were asked how frequently they brushed, flossed, and had checkups. They were also asked about the thoroughness with which they brushed and flossed, and about the advantages and disadvantages of all three behaviors. Descriptive statistics were calculated. RESULTS: The response rate was 72%. While 97% of subjects reported brushing at least once a day and 32% reported flossing at least once a day, 13% indicated they did not brush all teeth or all parts of teeth, and one-third of those who said they flossed daily did not floss all teeth. Seventy-three percent of respondents reported getting dental checkups at least once a year. For brushing, insufficient thoroughness was more commonly a problem than insufficient frequency. CONCLUSIONS: Patient education efforts related to brushing will probably be more effective if they focus on thoroughness rather than frequency. Interventions to increase flossing should probably focus on overcoming skill deficits. PMID- 7996215 TI - Update on clinical attire requirements in dental hygiene programs. AB - PURPOSE: Many changes have occurred in the clinical appearance of dental hygienists in the past few years because of increased emphasis on infection control and disease prevention. The purpose of this study was to assess dental hygiene program clinical attire requirements in 1993 and to compare them with requirements as described by a 1988 survey. METHODS: Checklist questionnaires were mailed to the directors of all 211 dental hygiene programs in the United States and Puerto Rico in October 1993. Questions were asked regarding clinical attire requirements for students and faculty, including uniforms, gowns, lab coats, masks, protective eyewear, shoes, hair coverings, laundry management, and changes under consideration. Percentages were calculated by region and for all responding programs. RESULTS: Of 211 questionnaires mailed, 178 were returned, for a response rate of 84%. Results indicated that students and faculty are currently wearing more colorful uniforms and scrubs than in 1988. Long-sleeved lab coats, disposable gowns, and washable surgical gowns are increasing in use. Glasses and face masks were required for all students and faculty in both surveys, but chin-length face shields are increasing in use as optional face protection. In most instances, face shields are worn with face masks. Laundry services are being provided for faculty (employees); however, most students continue to be responsible for their own laundry after being instructed to follow stringent guidelines taught by the faculty. CONCLUSIONS: Increasing emphasis on personal and patient protection is moving clinical attire requirements toward a more surgical appearance. Dental hygiene educators continue to monitor and to stay current with federal infection control recommendations, regulations, and guidelines. PMID- 7996216 TI - The California demonstration project in independent practice. PMID- 7996217 TI - Care for the children. PMID- 7996218 TI - Issues in patient care delivery. Interview by Marie Manthey. PMID- 7996219 TI - Nurses and patient assessment. PMID- 7996220 TI - Performance improvement through quality improvement teamwork. AB - Quality improvement teams have the ability to enhance processes that impact care delivery. Organizations must use a framework for documentation and communication of the team's work that is congruent with expectations by the Joint Commission on Accreditation of Healthcare Organizations (JCAHO) and that nurse executives can apply the expectations to the activities of their departments. The author discusses one such framework, based on 1994 standards, and presents a team report form illustrating communication of the team's efforts using JCAHO terminology. PMID- 7996221 TI - Integrating patient satisfaction with a quality improvement program. AB - Meeting and exceeding customers' expectations is the heart of any quality improvement program. The authors describe the development of a survey tool designed to assess patient satisfaction and its role in the hospital's total quality management initiative. PMID- 7996222 TI - The clinical technician as a member of the patient-focused healthcare delivery team. AB - Change is an integral component of hospital operations. The patient care delivery system is not exempt from the forces of change. Ingalls Memorial Hospital has developed the role of the clinical technician to enhance patient-focused care philosophy. This clinical technician program has successfully achieved patient focused care without physical restructuring; it has increased patient satisfaction, staff satisfaction, continuity, and quality of care. PMID- 7996223 TI - Preceptor, mentor, and sponsor roles. Creative strategies for nurse retention. AB - As nurse executives and managers struggle to decrease the costs of providing direct care to patients, the hidden expense related to staff turnover should be examined. The authors present a framework for identifying the needs of staff nurses related to preceptors, mentors, and sponsors, and suggest that meeting these needs may enhance retention and reduce the high costs of nurse turnover. PMID- 7996224 TI - Developing case management plans using a quality improvement model. AB - Case management plans are viable tools currently used to control healthcare cost and improve quality. The authors present a quality improvement-case management framework to guide nursing and hospital administrators in the development of these plans and to answer any questions they might raise while struggling through the process. PMID- 7996225 TI - Organizational tax status, values, and nursing. PMID- 7996226 TI - Reengineering hospitals using the "function follows form" model. AB - The author discusses some of the problems and shortcomings of the process used by many outside consultants to assist hospitals reengineer their operations. The author calls this process the "form follows function" process because employees are involved extensively in redesigning job tasks (functions) that in turn change the organization's structure, positions, and reporting relationships (form). The author presents an alternative process called the "function follows form" model used by two consultants to assist six hospitals in a multihospital system reengineer their operations. The process resulted in documented quantifiable improvements in enhanced quality, service, and financial outcomes in the first year of implementation. PMID- 7996227 TI - Essential resources: compact disks for computers. PMID- 7996228 TI - Mexico's healthcare system. PMID- 7996230 TI - Waltham Symposium on the Nutrition of Companion Animals. Proceedings of a meeting at the 15th International Congress of Nutrition. Adelaide, South Australia, September 23-25, 1993. PMID- 7996229 TI - John Rivers (1945-1989): his contribution to research on polyunsaturated fatty acids in cats. AB - John Rivers was a remarkable person, with enormous courage and a very generous spirit. He made a significant and long-lasting impact on the science of nutrition, disaster relief and the lives of those with whom he worked. His contribution to the understanding of the essential fatty acid requirements and metabolism in the cat while working at the Nuffield Institute of Comparative Medicine is described in this paper, together with background information on the polyunsaturated fatty acid research undertaken in the Biochemistry Department at the Institute. PMID- 7996231 TI - Assessment of the nutritional adequacy of pet foods through the life cycle. AB - Despite the lack of precise information on the requirements for many of the nutrients essential for cats and dogs and the paucity of information on the availability of nutrients in foods, many commercial diets support excellent growth, reproduction, and maintenance. However, these diets use empirical information that cannot be readily applied to the formulation of new diets. Progress in companion animal nutrition requires more precise information on requirements for various life stages (especially reproduction and maintenance), along with values for the bioavailability of nutrients in dietary ingredients. There is virtually no information on the bioavailability of nutrients for companion animals in many of the common dietary ingredients used in pet foods. These ingredients are generally byproducts of the meat, poultry and fishing industries, with the potential for wide variation in nutrient composition. Claims of nutritional adequacy of pet foods based on the current Association of American Feed Control Official (AAFCO) nutrient allowances ("profiles") do not give assurances of nutritional adequacy and will not until ingredients are analyzed and bioavailability values are incorporated. The AAFCO feeding test provides a superior method for assessing nutritional adequacy to the profile, although the current protocol has procedural and interpretative limitations. PMID- 7996232 TI - The Association of American Feed Control Officials Dog and Cat Food Nutrient Profiles: substantiation of nutritional adequacy of complete and balanced pet foods in the United States. AB - The Association of American Feed Control Official (AAFCO) formed the Canine (1990 1991) and Feline (1991-1992) Nutrition Expert Subcommittees to update the requirements for substantiation of "complete and balanced" claims for pet foods sold in the United States. There are two means by which a company may substantiate nutritional adequacy for a dog or cat food. The first means is by formulating the food so that nutrient levels fall within the ranges as established in the AAFCO Dog and Cat Food Nutrient Profiles. These profiles replace the National Research Council recommendations as the recognized authority in the United States as that term is applied to AAFCO regulations. Levels of nutrients are based on practical formulations of pet foods with adjustments to account for bioavailability of nutrients in commonly used ingredients. Separate profiles for adult maintenance and growth and reproduction are set, and maximum levels of some nutrients are also established. The second means of substantiation is through the conduct of feeding trials following AAFCO protocols. PMID- 7996233 TI - Microbial degradation of taurine in fecal cultures from cats given commercial and purified diets. AB - Freshly passed feces were collected from cats (n = 5-7) given cooked and uncooked commercial canned-type diets, casein and soy protein containing purified diets and a commercial extruded diet. The feces were anaerobically cultured in medium containing either taurine, taurocholic acid or [2-3H]taurine for 24 h at 37 degrees C. Taurine degradation in cultures was greatest for cultures from cats receiving diets reputed to cause taurine depletion. Diaminopimelic acid in feces indicated that differences in taurine degradation rate among groups was associated with differences in bacterial numbers in feces. After 6 h of incubation, < 10% of taurocholate and > 60% of taurine remained. Nearly all the tritium on the labeled taurine was recovered as water. These results indicate that deconjugation and deamination are the initial steps in microbial catabolism of taurocholic acid and that enteric microbial growth may be a major determinant of dietary taurine requirement of cats. PMID- 7996234 TI - Fecal bile acid excretion and taurine status in cats fed canned and dry diets. AB - Cats conjugate their bile acids with taurine but are unable to synthesize sufficient quantities of this amino acid to meet their needs. To maintain the same blood taurine level, canned foods must contain more taurine than dry foods. In the present study we examined the effect of soluble fiber on fecal bile acid excretion and taurine status and compared the quantity and profile of fecal bile acids in cats fed canned and dry diets. In a cross-over design, 10 adult cats were fed a typical canned diet containing 0.25% kappa carrageenan with or without the addition of 0.5% guar gum (2.5% on a dry matter basis) for 6 wk. All cats were then transferred to a dry diet. The addition of guar gum to the canned diet had no significant effect on taurine status, but the dry diet, which contained less taurine than the canned diet, resulted in an increase in plasma taurine. With the dry diet, total bile acid excretion was reduced by approximately 65%. The profile of bile acids in feces was also radically different with a marked decrease in secondary bile acids. This work suggests that when canned rather than dry diets are fed, the conversion of primary to secondary bile acids is greater and is indicative of an alteration in the activity of the gut flora that may lead to an increase in taurine degradation. PMID- 7996235 TI - The taurine requirement of the kitten fed canned foods. PMID- 7996236 TI - Dietary glycine: its importance in growth and development of the budgerigar (Melopsittacus undulatus). AB - Birds have a high demand for the amino acid glycine due to its involvement in uric acid biosynthesis. Because the ability to synthesize glycine may be limited in the immature liver of young birds, glycine is usually considered to be semiessential in the diet of newly hatched chicks. This study investigated the effects of supplementary dietary glycine on growth and development in budgerigar chicks. Eighteen pairs of breeding budgerigars were randomly assigned to one of three dietary treatment groups. Each pair of birds was offered a seed-based diet and a rearing food that was used as the supplementation medium. One group received an unsupplemented rearing diet (2.7 g glycine/kg), whereas the remaining groups received diets supplemented with 15.0 and 30.0 g glycine/kg, respectively. Sixty-seven chicks were reared with records kept of growth and survival rates. A dietary glycine supplement tended to enhance the growth rate of budgerigar chicks, although this was not significant. There was no influence of diet on the rate of feather growth or the number of chicks that survived to adulthood. Follow up measurements, conducted 1 y later, indicated that a dietary glycine supplement during development had long-term morphological effects. Bodyweight, tarsus length and beak width were all significantly greater in adult budgerigars that had received the highest level of glycine supplementation as chicks. PMID- 7996237 TI - The effect of dietary levels of folate and cobalamin on the serum concentration of folate and cobalamin in the dog. PMID- 7996239 TI - Effect of carbohydrates on digestion in the cat. PMID- 7996238 TI - Blood sugar levels and renal sugar excretion after the intake of high carbohydrate diets in cats. AB - The effect of starch and sugars on blood sugar level and renal excretion of sugars and galactitol was investigated. Fifty-nine adult cats were divided into seven dietary groups (carbohydrate content in dry matter): STARCH (29-37% starch, decomposed or raw), SUC (36% sucrose), LAC1 and LAC2 (11 and 28% lactose, respectively), GLUC (40% glucose), GAL (39% galactose) and a carbohydrate-free control diet, FAT. Diet STARCH did not significantly influence postprandial blood glucose level (3.65 +/- 0.68 mmol/l +/- SD, n = 16) compared with diet FAT (3.20 +/- 0.77 mmol/l, n = 14) 1, 3 or 6 h after feeding (weighted means). Diet GLUC led to a steep rise in blood glucose concentration 1 h after feeding (5.08 +/- 0.69 mmol/l, n = 6). Diet SUC induced a mild persistent hyperglycemia without marked postprandial changes (4.52 +/- 0.52 mmol/l, n = 15, weighted mean of 0, 3 and 6 h post-prandially). Diet GAL induced persistent hypoglycemia before and after feeding (2.58 +/- 0.38 mmol/l, n = 13) and considerable postprandial galactosemia (3.26 +/- 1.38 mmol/l, n = 7). In the groups STARCH and FAT, glucose was only detectable in traces in urine, whereas all diets containing sugars led to glucosuria. In group SUC, fructose and sucrose were found in urine and in both lactose groups galactose and lactose were found. Diet GAL led to galactosuria (140 mmol galactose/l). In group LAC1, and especially in group GAL, galactitol was detected in urine. These results point to a rather limited capacity of the cat to metabolize sugars. PMID- 7996240 TI - Absorption and retention of zinc when administered as an amino-acid chelate in the dog. PMID- 7996241 TI - Zinc source influences zinc retention in hair and hair growth in the dog. PMID- 7996242 TI - Dietary iodine level and thyroid function in the cat. PMID- 7996243 TI - Vitamin E in exotics: effects, evaluation and ecology. AB - The pathophysiology and lesions associated with vitamin E deficiency are similar between domestic and exotic species, and circulating plasma concentrations are also similar between comparable groups. However, many ecological variables must be considered for the most relevant comparisons. Tissue values of vitamin E, apart from plasma, are unknown for most exotics. Dietary vitamin E requirements of exotic species and domestics appear to differ; based on natural foodstuff analyses and clinical observations, between 50 and 200 mg vitamin E/kg DM are necessary to prevent vitamin E deficiency, 5- to 10-fold higher than current livestock recommendations. PMID- 7996244 TI - Design of digestibility trials for dogs and cats. PMID- 7996245 TI - Energy needs of companion animals: matching food intakes to requirements throughout the life cycle. AB - An animal's primary demand from its diet is for energy. Unlike an individual nutrient, there is no range of acceptable intakes, but rather a specific energy requirement for a given set of conditions. Accurate assessments of both food energy density and the energy needs of the animal are implicit in providing reliable feeding recommendations. The metabolizable energy content of a food is best measured using in vivo testing in the target species. However, the demands of biological testing mean that a set of factors is desirable to provide reasonable estimates. Assessment of energy requirement in dogs is confounded by their wide range of body weights. It should be expressed on an allometric basis, but the precise value for the exponent is still a matter of some debate. For cats recent studies suggest there may be an allometric relationship over a weight range of 2.5-6.5 kg. Energy requirement is dependent on a number of other factors, in particular, activity, environmental temperature and life stage. Demand increases most in lactation (four times) and growth (up to three times). Old animals show a decline in energy requirement, but this may reflect principally a decrease in activity, rather than any underlying change in metabolism. PMID- 7996246 TI - Use of the doubly-labeled water method to assess energy expenditure in free living cats and dogs. AB - The doubly-labeled water method uses naturally occurring stable isotopes of water (H2 18O and D2O) to assess energy expenditure, body composition and water flux in animals and humans. The technique is relatively noninvasive (a few blood or urine samples over 2 wk) and is performed in free living conditions during a period of between 5 and 20 d. This is the first report of the use of the method in three cats and two dogs. The measured energy expenditure during 11 d was 207 +/- 12 and 263 kJ.kg-1.d-1 for cats and dogs, respectively. These values were 30 and 10% lower, respectively, than NRC recommendations for energy requirement (NRC 1985, NRC 1986). The percentage body fat was 23 +/- 5% in the three cats and 35% in the two dogs used in this study. The water output (urine + breath) was 36 +/- 4 ml.kg 1.d-1 for the cats and 60 ml.kg-1.d-1 for the dogs. Of the water output, 23% (cats) and 17% (dogs) was lost as insensible water loss. The precision and accuracy of the method are discussed in relation to the assumptions made with this technique and by comparison with published values. PMID- 7996247 TI - Usefulness of dual energy X-ray absorptiometry for body composition measurement in adult dogs. PMID- 7996248 TI - Energy requirements of adult female beagles. AB - The energy requirements of 19 intact adult female beagles were determined over a 60-wk period. The initial age of the dogs averaged 6.5 y (range 0.8-13.4) and the initial weight averaged 11.0 kg (range 8.7-13.7). Dogs were housed in groups of four in heated indoor-outdoor kennel runs. Dogs were fed daily a commercial dry dog food that contained 13.8 kJ/g. The amount offered was adjusted to maintain body weight. Daily energy intake ranged from 2227 to 3667 kJ/dog, with an average of 3061 kJ/dog. When adjusted for differences in body weight, average daily energy intake ranged from 482.6 to 803.1 kJ/kg body weight0.67 with a mean of 617.5 kJ/kg0.67. Energy intake (kJ/kg body weight0.67) declined with age and could be described by the nonlinear equation Y = 753 x age-0.1321; r = -0.802. When these data are combined with an earlier study, the energy intake (kJ/kg body weight0.67) of this group of 36 dogs could be described by the equation Y = 767 x age-0.1408; r = -0.777. These data demonstrate that canine energy requirements decline with age and that the National Research Council recommendations of 552 kJ/kg body weight0.75 overestimates the requirements of adult dogs 3 y of age and older. PMID- 7996250 TI - The practicalities of measurement and interpretation of field metabolic rate in dogs. PMID- 7996251 TI - Maintenance energy requirement of five popular species of ornamental fish. PMID- 7996249 TI - Energy metabolism and nutrient oxidation in the pregnant mink (Mustela vison) as a model for other carnivores. AB - The mink is a strict carnivore and a seasonal breeder, which may be used as an experimental model for other carnivores. The present investigation comprised a total of 44 balance experiments, each including a 24-h measurement of heat production by indirect calorimetry, carried out from mating until close to parturition. For observations with a nonprotein respiratory quotient between 0.7 and 1.0 (n = 42), quantitative oxidation of nutrients was calculated. The weight gain of the uterus during pregnancy was studied in 41 females killed either before mating, before implantation, after implantation or in mid or late true gestation, and energy retention was calculated. Heat production did not increase with advancing stage of gestation. Mean energy retention was low and in some individuals with repeated measurements even negative, indicating that part of the energy requirement for pregnancy may be supplied by mobilization of body reserves. This was reflected by a high level (42%) of fat oxidation in relation to total heat production. Protein oxidation accounted for 38% of heat production. The weight gain of the uterus during pregnancy could be described by logarithmic functions. Energy deposition in fetal tissue was low and only averaged approximately 350 kJ 47 d after mating. PMID- 7996252 TI - The repeatability of body composition measurements in dogs and cats using dual energy X-ray absorptiometry. PMID- 7996253 TI - Changes in the body composition of the domestic shorthaired cat during growth and development. PMID- 7996254 TI - Body composition of male and female Labrador retriever puppies at 20 wk of age. PMID- 7996256 TI - Handrearing of orphaned puppies and kittens. PMID- 7996255 TI - Growth of juvenile green iguanas (Iguana iguana) fed four diets. AB - Wild green iguanas consume a primarily folivorous diet. As pets in captivity, they suffer high mortality and malnutrition. Nutrient requirements are not established. The purpose of this study was to compare growth in juvenile iguanas fed three commercial diets and a romaine-based diet. Twelve nominally 4-wk-old iguanas were fed in a latin square design each of four diets for 8 wk, consisting of a 2-wk accommodation period and a 6-wk collection period. Diets were analyzed at the beginning and end of the study. Food consumption was measured daily; body weights and lengths were measured weekly. For Diets A, B, C and D mean body weight gains were--3, 6, 31 and 60% in 6 wk, respectively. Gain in body weight and snout-vent length increased linearly with dietary protein and fiber and with dry matter intake. The data suggest that growth in pet green iguanas may achieve rates for farmed and wild green iguanas when diets are palatable and contain adequate protein and fiber. PMID- 7996257 TI - Nutrition of ornamental fish: water soluble vitamin leaching and growth of Paracheirodon innesi. PMID- 7996258 TI - The nutrition of the canary (Serinus canarius). PMID- 7996259 TI - Effect of three different preservative systems on the stability of extruded dog food subjected to ambient and high temperature storage. AB - Three different preservative treatments were applied to extruded dog food. After processing the dog foods were placed in bags and stored for 16 wk at 48.8 degrees C for 12 mo at 22.2 degrees C. The preservative treatments were as follows: 1) ethoxyquin and butylated hydroxyanisole (EX/BHA), 2) mixed tocopherols (TC/TC) and 3) ascorbyl palmitate and mixed tocopherols (ATL/TC). There were no significant differences among treatments for thiobarbituric acid values for either the high or ambient temperature tests, whereas peroxide value (PV) showed significant treatment and storage effects. For products stored at 22.2 degrees C, PV increased linearly from week 4 to week 16 in both the TC/TC and ATL/TC preservative treatments and was significantly higher than the PV for EX/BHA. In the ambient temperature test, the PV was also higher for the TC/TC and the ATL/TC treatments compared to the EX/BHA treatment after 5 and 12 mo of storage. Results of the sensory evaluations were closely associated with PV. In both the high and ambient temperature tests the dogs consumed more of the foods with the lowest PV when given a two-bowl choice. Using PV and sensory tests as criteria, we concluded that the ATL/TC and TC/TC preserved dog foods deteriorated during storage compared to the EX/BHA preserved food in both the high and ambient temperature tests. PMID- 7996261 TI - Struvite diet in cats: effect of ammonium chloride and carbonates on acid base balance of cats. AB - Six healthy adult cats were fed a basal minced beef meat and rice diet (one meal per day) with varying amounts or combinations of acidifying and alkalizing additives (ammonium chloride, calcium and sodium carbonate). The base excess in the food (mmol/kg dry matter) was calculated (data on food compounds in g/kg dry matter) as follows: base excess = 49.9*Ca + 82.3*Mg + 43.5*Na + 25.6*K-64.6*P 13.4*met-16.6*cys-28.2*Cl. Base excess in the experimental diets amounted to between +305 and -1079 mmol/kg dry matter. After an adaptation period of 5 d, urine and blood pH as well as water and mineral balance were determined in the cats over a 10-15-d period. The daily mean urine pH ranged between 6.1 and 7.8. There was a highly significant correlation between the base excess in the food and the mean urine pH. The regression line was linear down to a base excess in the diet of approximately -400 to -500 mmol/kg dry matter and a pH in the urine of 6.2. The postprandial increase of urine pH was suppressed either by large amounts of ammonium chloride (> 780 mmol/kg dry matter) alone or in combination with calcium carbonate but not in combination with sodium carbonate. The relationship between the decrease of the blood pH and the amount of ammonium chloride added to the diet was more marked than the relationship between blood pH and base excess in the food.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7996260 TI - Lower urinary tract disease in cats--new problems, new paradigms. AB - Companion animal diets may be related to prevention, pathogenesis and/or treatment of diseases of the lower urinary tract. For example, urolithiasis can be either diet induced or nutrient sensitive. One of the most interesting developments in veterinary urolithiasis research has been the recent change in the composition of stones recovered from cats. In 1984, 88% of stones analyzed by quantitative methods were > 70% struvite, whereas < 1% were calcium oxalate. In 1992, the percentage of struvite had dropped to 62, whereas the percentage of calcium oxalate had increased to 24. Another recent development in lower urinary tract disease of cats is the recognition that urolithiasis appears to be a minor cause of the signs of frequency, urgency and hematuria for which patients are presented. This suggests that diet may no longer be involved, or be involved in previously unrecognized ways, in many current cases of this disease. Some of these feline patients may have a disease similar to interstitial cystitis, a disease of humans that appears to be of neuroepithelial origin. Our laboratory has been studying this possibility recently, and many similarities between the two diseases have been found. PMID- 7996263 TI - Nutritional management of gastrointestinal tract diseases of dogs and cats. AB - Pharmaceutical agents are often given inappropriate precedence in the treatment of gastrointestinal tract diseases. Nutrients have marked influences on the gastrointestinal tract and manipulation of the diet provides clinicians with a powerful therapeutic strategy to be used alone or concurrently with drug therapy. During acute gastroenteritis a change from the animal's regular food to a diet containing novel protein sources minimizes the likelihood of acquired food allergies to the staple protein components of the diet. "Feeding through" diarrhea, a method used in human infants, has limited applicability in dogs and cats. The ideal diet for chronic small bowel-type diarrhea is highly digestible, gluten-free, hypoallergenic, isosmolar, low in fat and low in lactose. Dietary protein requirements increase in protein-losing enteropathy. Dietary fat is kept to a minimum during gastrointestinal dysfunction because malabsorbed fatty acids and bile acids cause secretory diarrhea. In diseases of the small bowel, it is traditional to use low fiber diets. This recommendation needs revision because the binding and gelling properties of fiber are of potential benefit in the treatment of small bowel diarrhea. High fiber diets are useful in most large bowel diseases. The specific fiber type used markedly influences the clinical result. PMID- 7996262 TI - Dietary management of naturally occurring chronic renal failure in cats. PMID- 7996264 TI - Diet-induced cholecystokinin release in cats. PMID- 7996265 TI - Evaluation of nutrient utilization in the canine using the ileal cannulation technique. AB - Nine mature mongrel dogs were used to evaluate a surgical technique for the cannulation of the terminal ileum and used in two experiments to determine the effect of carbohydrate source on starch and dry matter digestion. Dogs (16.2 +/- 2.0 kg body weight; means +/- SD) were fitted with an ileal T-cannula constructed of polyvinyl chloride pipe. The cannula was inserted into the terminal ileum approximately 10 cm proximal to the ileocecal junction and the cannula was exteriorized through a small incision on the right flank. Dogs recovered quickly from surgery (5d). A preliminary study using Cr:EDTA in the food indicated that sampling for 12 h postprandially allowed near complete representation of digesta flow for a meal; peak flow occurred 4-to 8-h postfeeding. Two experiments were performed evaluating the effect of carbohydrate source on ileal starch and dry matter digestibility. Dogs were fed two meals daily with Cr2O3 used as a digesta marker. Diets contained 67% extruded grain (corn, rice, oats or barley) and 33% canned meat supplement on a dry matter basis. Starch digestion was complete (> 98%) within the small intestine and was unaffected by carbohydrate source. In experiment 1, prececal and total tract dry matter digestibilities were higher for rice than corn, and in experiment 2, barley was higher than oats. The ileal T cannula allows for measurement of small intestinal nutrient disappearance without the confounding effects of colonic microflora. This method may be useful when applied to the study of other nutrients in dogs. PMID- 7996266 TI - Protein-deficient diet alters serum alkaline phosphatase, bile acids, proteins and urea nitrogen in dogs. PMID- 7996267 TI - Long-term voluntary fasting in adult obese cats: nitrogen balance, plasma amino acid concentrations and urinary orotic acid excretion. PMID- 7996268 TI - Body condition of cats. PMID- 7996269 TI - Hemosiderosis and dietary iron in birds. PMID- 7996270 TI - Case report: efficacy of oral carnitine therapy for dilated cardiomyopathy in boxer dogs. AB - This paper investigates the role of carnitine in the etiology and treatment of dilated cardiomyopathy in boxers. Two boxers were diagnosed as having dilated cardiomyopathy on the basis of clinical presentation, chest radiographs, electrocardiography and echocardiography. In one dog, carnitine was administered at 6.0 g (or approximately 250 mg/kg live weight (LW) daily per os, and this dog remained asymptomatic for 4 mo until it presented for anorexia, coughing and weakness. Necropsy and histologic findings were consistent with boxer cardiomyopathy in both dogs. Cardiac carnitine concentration was 567 nmol/g wet weight in the unsupplemented dog, which is below the normal mean +/- SD concentration of 1493 +/- 141 nmol/g wet weight. Low cardiac carnitine concentrations appear to be a consistent finding for dilated cardiomyopathy in boxers. However, in the dog that received carnitine therapy, cardiac carnitine was 2802 nmol/g wet weight, and all tissues assayed in the supplemented dog had higher carnitine concentrations than normal dogs. Elevation of tissue carnitine failed to ameliorate dilated cardiomyopathy in this dog. Oral carnitine supplementation in these therapeutic doses appears not to resolve dilated cardiomyopathy in all boxers. PMID- 7996271 TI - Diet as a risk factor for feline external odontoclastic resorption. PMID- 7996272 TI - Effect of level and source of dietary fiber on food intake in the dog. AB - The effects of dietary fiber on challenge meal intake and on the perception of hunger in dogs were evaluated. A program of testing variants of a standard low energy diet, to which one of five fiber containing raw materials was added, was undertaken. Diets were fed to a group of six dogs for 12-d periods in a latin square design and in amounts that corresponded to the food allowance for weight reduction. Behavioral characteristics of dogs were recorded on videotape for 30 min periods after introduction of test diets. On two occasions during each 12-d feeding period dogs were presented with a challenge meal. At the end of each 12-d feeding period all dogs entered a 6-d washout period. There was no significant effect of diet on the intake of the challenge meal or on intake of food during the subsequent washout period. In addition, diet had no apparent effect on the perception of hunger, as represented by behavioral characteristics during the 30 min period after presentation of test diets. It was concluded that inclusion of moderate levels of raw materials, composed primarily of insoluble fiber, in a commercial low energy diet had no apparent beneficial effects on satiety, when fed to dogs on an energy intake corresponding to allowances for weight reduction. PMID- 7996273 TI - Source of dietary fiber and its effects on colonic microstructure, function and histopathology of beagle dogs. PMID- 7996274 TI - Does the canning process alter the physiological effects of dietary fiber in the dog? PMID- 7996275 TI - Composition of meal influences changes in postprandial incremental glucose and insulin in healthy dogs. AB - Postprandial hyperglycemia and insulin secretion depend on many factors, such as food composition, carbohydrate type and processing. The purpose of this study was to evaluate the effects of foods differing in composition in nonobese clinically normal dogs. These dogs were offered in a single meal one of the four foods. Blood samples were collected before feeding and during the 180 min after the meal. Plasma glucose and insulin concentrations were determined. The integrated areas under the postprandial glucose and insulin response curves were calculated. Times to response peaks, maximum plasma insulin elevation, area under the insulin response curve and the insulinemic index differed between dog foods. Crude fiber content had no significant effect. The time to glucose peak was higher and the time to insulin peak lower with the food highest in protein and ether extract content. The time to glucose peak was correlated to protein, fat and nitrogen free extract content of foods, whereas the time to insulin peak and the area under the insulin curve were correlated to protein and nitrogen-free extract. PMID- 7996276 TI - Canned high fiber diet and postprandial glycemia in dogs with naturally occurring diabetes mellitus. PMID- 7996277 TI - Stool characteristics, gastrointestinal transit time and nutrient digestibility in dogs fed different fiber sources. PMID- 7996278 TI - Fermentability of selected fibrous substrates by dog fecal microflora as influenced by diet. PMID- 7996279 TI - Fermentability of selected fibrous substrates by cat fecal microflora. PMID- 7996280 TI - Nutrition and equine performance. AB - Some aspects of energy, protein and vitamin E nutrition of the performance horse are discussed. The amount, dietary source and time of ingestion of energy before exercise can influence performance. In 1989 the National Research Council (NRC) increased their estimates of energy required by racehorses. Recent studies indicate that the increase was reasonable. Many factors, however, can influence energy requirements. Therefore, the best measure would be body weight and composition of the horse. A proper balance of soluble carbohydrate, fiber, fat and protein is essential. Some guidelines are presented. The amount and type energy source given before exercise can influence level of plasma glucose and free fatty acids during exercise, but the effects of these changes in the concentration of metabolites remains to be determined. There is no evidence that increased dietary concentrations of protein are needed and, in fact, may impair performance. Supplemental histidine (to enhance carnosine levels) or carnitine appear to be of limited value for horses fed conventional diets. Dietary concentrations of vitamin E less than the 80 IU/kg recommended by NRC seem to adequately protect against exercise-induced peroxidation. The NRC value may be justified on the basis of immune response, but further studies are needed. Vitamin E has been shown to be involved with familial equine degenerative myeloencephalopathy and may be involved with equine motor neuron disease, a condition considered to be similar to amyotrophic lateral sclerosis in humans. PMID- 7996281 TI - Ergogenic aids to performance in the race horse: nutrients or drugs. AB - Since the domestication of the horse and its use in various types of athletic competition, its diet has developed from that associated with grazing to feeding of additional energy in the form of grains up to the present situation when numerous supplements are fed in hopes of enhancing performance. Many if not all of these may be considered as ergogenic aids, and under the rules of racing in many countries should be considered as a prohibited substance. Until recently, a blind eye has been turned to whether the rules should be enforced against many nutritional supplements, for example, vitamins and amino acids, especially when given in amounts vastly in excess of normal requirements. However, although arguably a nutrient, large doses of sodium bicarbonate and possibly other compounds with the potential of improving buffering capacity have been used extensively, and rules and detection methods have been introduced to curtail this. This paper reviews the nutritional supplements currently in use and discusses whether the singling out of alkalinizing agents as an enforceable prohibited substance is justified, whereas other substances such as fats can be supplemented in high amounts. PMID- 7996282 TI - Plasma [H+] responses to exercise in horses fed a high-fat diet and given sodium bicarbonate. PMID- 7996283 TI - Blood lactate concentration during exercise in horses fed a high-fat diet and administered sodium bicarbonate. PMID- 7996284 TI - The effects of an oral glucose polymer on muscle glycogen resynthesis in standardbred horses. PMID- 7996285 TI - Prevention of acidosis and laminitis associated with grain feeding in horses. PMID- 7996286 TI - Optimal nutrition for athletic performance, with emphasis on fat adaptation in dogs and horses. AB - Four mathematical approaches are proposed to determine optimal ranges of nutrients for specified purposes. For exercise, the diet must provide optimal mixtures of fuels, also optimal amounts of nutrients conducive to a sound structure, a desired power/weight ratio, a water-electrolyte system that resists dehydration and buffers hydrogen ions, a tolerance to the cumulative stress of repetitive competition and tractable attitude. The nutritional strategy of carbohydrate loading risks a variety of abnormalities in dogs and horses. An alternative strategy of fat adaptation (the combination of fat feeding and training) was found to improve aerobic performance in dogs and horses and to spare glycogen utilization and reduce lactate accumulation. Surprisingly, improved anaerobic performance has also been confirmed in fat-adapted horses that have been sprint trained. Fat adaptation increased the blood lactate responses to incremental tests and repeated sprints. Blood lactate accumulation during repeated sprints was affected synergistically by the combination of fat adaptation and sodium bicarbonate supplementation. Fat adaptation in horses appears to facilitate metabolic regulation to achieve power needs, with glycolysis decreasing during aerobic work but increasing during anaerobic work and with blood lactate changes following accordingly. Interactions between fat adaptation and dietary cation-anion balance need further investigation. PMID- 7996287 TI - Lipid metabolite responses to diet and training in sled dogs. AB - Two groups of Alaskan Huskies were fed either a high fat (HFD) or a high carbohydrate diet 4 wk before and during an 8-wk conditioning program. Aerobic bouts of exercise were performed before and after conditioning. Blood samples taken before and after each exercise test were analyzed for serum concentrations of free fatty acids (FFA), triglycerides (TG), vitamin E, glucose and serum lipase activity. The post-exercise FFA and TG values were greater in the HFD group both before and after training. There were no significant differences in plasma vitamin E or in serum lipase activity between diet groups. It is concluded that after an adequate period of adaptation, prolonged feeding of a HFD safely enhances the availability of local and peripheral lipid stores during exercise. Although the elevated levels of FFA and TG associated with HFD suggest enhanced potential for performance, further study of more prolonged and possibly more intense exercise is necessary to confirm this theory. PMID- 7996288 TI - Blood changes during training and racing in sled dogs. AB - Six male and six female Alaskan Huskies allocated three by three to two teams fed rations slightly different in protein/fat ratio (A, 29.2: 53.7%; B, 34.1: 48.5% of digestible energy) were studied for hematological and metabolic changes during a complete training and racing season (24 wk). Blood variables [packed cell volume (PCV), red blood cell count (RBC), mean corpuscular volume, hemoglobin, total plasma protein, free fatty acids, cholesterol, lactic acid, creatine phosphokinase (CPK), creatinine, alanine aminotransferase (ALT) and aspartate aminotransferase (AST)] and six minerals were determined before (at rest) and immediately after a test run of 9 km and then 10, 20 and 30 min later, at the beginning of training as well as 7, 20 and 24 wk later. Training and exercise both significantly influenced PCV, RBC, creatinine and ALT and exercise influenced CPK. Only negligible differences were found between the diets. PMID- 7996290 TI - Mental status changes and stroke. AB - OBJECTIVE: To determine the frequency with which an acute confusional state is caused by a stroke and to evaluate the usefulness of obtaining computed tomography scans in this setting. DESIGN: Retrospective analysis. SETTING: Tertiary referral center. PATIENTS: The authors reviewed 127 neurology consultations requested for patients presenting with acute and apparently isolated mental status changes. The mean age was 62 years. RESULTS: Nine (7%) of the 127 patients were thought to have suffered mental status changes as a result of an acute stroke: one subarachnoid hemorrhage, and eight ischemic strokes. There was no intracerebral hemorrhage. The locations of the infarcts were: right frontoparietal (four patients), bilateral occipital (two patients), bilateral frontal (two patients), and right pontine (one patient, for whom the causality of the stroke was uncertain). Of those nine stroke patients presenting with isolated mental symptoms, six (66%) had some focal abnormality on neurologic examination. Only three (2.7%) of the 109 patients with no focal findings were ultimately diagnosed as having strokes, and one of these had a subarachnoid hemorrhage. CONCLUSIONS: Stroke was a relatively rare cause of acute confusional syndrome. The neurologic examination had a very high negative predictive value (97%) and was reliable in selecting patients who should undergo an imaging study. PMID- 7996289 TI - A decision aid for referring patients with systolic murmurs for echocardiography. AB - OBJECTIVE: To describe the practice pattern of a group of primary care providers in ordering echocardiography for healthy patients and to derive a decision aid to identify patients with systolic murmurs who have significant cardiac lesions. DESIGN: Retrospective case review of clinical variables, including the demographic, historical, and physical examination features obtained from chart review of the physician evaluation prior to referral for echocardiography and the echocardiographic results, with both univariate and multivariate regression analyses used to identify variables predictive of positive echocardiographic outcomes and to derive a regression model. SETTING: General internal medicine clinic in an urban major teaching hospital. PATIENTS/PARTICIPANTS: 169 patients between the ages of 18 and 55 years selected retrospectively from medical records. MEASUREMENTS AND MAIN RESULTS: Symptoms and auscultatory findings were not predictive of positive echocardiographic outcomes among the patients referred for the test. For the patients who had systolic murmurs, a logistic regression model had three significant predictors of positive echocardiographic results: additional year of age (odds ratio: 1.08, 95% CI: 1.02-1.13; p = 0.007); male gender (odds ratio: 5.87, 95% CI: 1.99-17.3; p = 0.002); and murmur grade > or = 3 (odds ratio: 4.99, 95% CI: 1.27-19.6; p = 0.02). The receiver-operating characteristic (ROC) curve area for this model was 0.741. If women aged 35 years and less with murmur grades < or = 2 had not been referred, 47% of the echocardiographies could have been avoided while retaining a sensitivity of 90%. CONCLUSIONS: The study suggested that healthy patients with systolic murmurs are least likely to have positive echocardiographic results when they are young and female and have murmur grades < or = 2. More careful screening of this group might make unnecessary almost half of the echocardiographies yielding negative results ordered for healthy patients with systolic murmurs. PMID- 7996291 TI - The effect of changing disease risk on clinical reasoning. AB - OBJECTIVE: To assess the ability of health care professionals to evaluate the effect of clinical test results in different settings. DESIGN: Subjects were presented with a series of generic clinical scenarios in which information about the test performance and the pretest probability of disease was varied. The subject estimates of posttest probability were compared with those calculated on the basis of Bayes' theorem. PARTICIPANTS: Fifty health care professionals, including 31 physicians and 19 nonphysicians, associated with a university teaching hospital. MEASUREMENTS AND MAIN RESULTS: Under a variety of testing conditions, both the physicians and the nonphysicians inaccurately estimated the posttest probability of disease. Based on a logarithmic transformation, the error in probability estimation was divided into a portion related to the pretest probability of disease and a portion related to the test performance. Most of the error in posttest probability estimation was associated with the incorrect use of pretest probabilities. The subjects consistently overestimated the posttest probability of disease expected under Bayes' theorem, with increasing error associated with decreasing pretest probability. Physician estimates of posttest probability increased with increasing likelihood ratios for each scenario. Nonphysician estimates of posttest probabilities increased with increasing likelihood ratios for a positive test, but the estimates associated with a negative test result were inconsistent. CONCLUSIONS: Physicians and nonphysicians overestimate posttest probabilities with increasing error associated with decreasing disease risk. Some nonphysicians may not fully understand the effect of test performance on risk estimation, particularly in the setting of a negative test. Health care professionals should receive training in the proper evaluation of test information, with particular emphasis on the influence of pretest disease risk on the posttest probability of disease. PMID- 7996293 TI - Violence against physicians. AB - OBJECTIVE: To ascertain the incidence of violence against internists. SETTING: A county-operated tertiary care center in Nassau County, New York. DESIGN AND PARTICIPANTS: Questionnaires were distributed to 100 internal medicine residents and attending physicians. They were asked to report: whether they had ever been assaulted or battered either by patients or by relatives of patients; the point in their medical training at which such episodes had occurred; the nature and severity of the violent episodes; and the circumstances surrounding such episodes. RESULTS: Questionnaires were returned by 63 physicians (response rate, 63%). Ten physicians (16% of the respondents) reported that they had been battered, three (5%) on multiple occasions. Twenty-six physicians (41%) reported that they had been assaulted, 15 (24%) on multiple occasions. The majority (54%) of violent episodes had been instigated either by intoxicated patients or by patients with psychiatric histories. In this small sample, no injury was reported. CONCLUSIONS: Violence against medical residents and attending physicians exists and is most commonly associated with patients who are intoxicated or who have psychiatric histories. PMID- 7996292 TI - Applicability of decision analysis to everyday clinical practice: a controlled feasibility trial. AB - OBJECTIVE: To determine whether decision analysis is applicable to routine management of suspected pulmonary embolism in an emergency care setting. DESIGN: Controlled feasibility trial. SETTING: Emergency center of a university hospital. PATIENTS: Outpatients (n = 84) admitted with clinical and scintigraphic evidence of pulmonary embolism. INTERVENTIONS: Patients were treated either with the usual clinical work-up for pulmonary embolism (control group) or using a decision analysis model with three options: no action: angiography followed by treatment if positive; treatment without angiography. RESULTS: All six senior residents in the decision analysis group agreed to fully participate for the 16 months of the study. Summarizing the decision analysis model in a graph was critical to obtain acceptance from all the physicians. Decision analysis (n = 43) and control (n = 41) patients underwent similar numbers of angiographies. However, angiographies for patients who had intermediate clinical probabilities of pulmonary embolism, between 25 and 75%, were more frequent in the decision analysis group (9/13 = 69%) than in the control group (7/20 = 35%). Agreement between clinical probability and lung-scan result was stronger in the decision analysis group. CONCLUSIONS: Decision analysis was successfully used to manage all patients suspected of having pulmonary embolism admitted to an emergency center during the 16-month trial. There was no insuperable obstacle to acceptance of clinical decision analysis by the physicians. Decision analysis may have resulted in a better discrimination between low and intermediate clinical probabilities of pulmonary embolism. PMID- 7996294 TI - Subsyndromal ("mixed") anxiety--depression in primary care. AB - OBJECTIVE: To determine in primary care settings the prevalence, clinical characteristics, and functional status of patients who have anxious and depressive symptoms who did not meet diagnostic criteria for major mood and anxiety diagnoses. DESIGN: Patients were screened with the General Health Questionnaire and interviewed if they exceeded the cutoff score of 5. Also, one patient whose score was below the cutoff was interviewed for every two patients whose scores were above the cutoff. SETTING: Five primary care sites in the United States, France, and Australia. PATIENT: Two hundred sixty-seven patients presenting to their primary care physicians for general medical care and follow up. METHODS: Structured diagnostic interviews were conducted and ratings of anxiety, depression, and functional impairment were obtained by trained interviewers. RESULTS: After adjustments for sampling, 5% of the patients had symptoms of anxiety, depression, and functional impairment, without meeting formal criteria for a major DSM-III-R mood or anxiety disorder. This was comparable to the prevalence of diagnosable DSM-III-R mood disorders but only one fourth the prevalence of diagnosable anxiety disorders. These patients who had subsyndromal symptoms had rates of lifetime psychiatric disorders and prior psychiatric treatment comparable to those of patients meeting criteria for major mood and anxiety disorders. CONCLUSION: The comparable rates of symptomatic distress, functional impairment, and prior psychiatric illness and treatment suggest that patients with subsyndromal anxiety and depressive symptoms warrant clinical recognition and possibly specific treatment. PMID- 7996295 TI - Policy statement for general internal medicine fellowships. Society of General Internal Medicine. AB - Fellowship programs in general internal medicine should be designed to train outstanding academic internists to serve as future faculty and leaders in the field. Although programs may vary widely in their specific components, all should share a number of characteristics and goals. In this document, the Society of General Internal Medicine outlines basic principles and guidelines for fellowship training, states that its own PCIM Directory will explicitly require that programs indicate how they conform to them, and indicates its interest in considering a formal fellowship accreditation process in the future. PMID- 7996296 TI - The use of videotape in internal medicine training. AB - By paying attention to the power of the medium and the method of feedback, videotaping programs can be a remarkably successful teaching and research tool. Learners can view their performance, review feedback on their own behavior, knowledge, and displayed attitudes, and develop plans to change behavior that can be followed up on subsequent tappings. In addition, trainees can share important experiences with each other and valued teachers. Interviewing skills can be documented and preserved, creating a video library that allows trainees to actually visualize improvements in their own performances over time. An archive of many such performances allows trainees, faculty, and researchers alike comparative access to the complex challenges of the medical interview. PMID- 7996297 TI - Screening for vitamin B12 deficiency in psychiatric patients. AB - Psychiatric patients are frequently screened for vitamin B12 deficiency in the absence of hematologic or other neurologic findings. To determine the yield of this practice, 162 psychiatric inpatients were screened for vitamin B12 deficiency. Ten patients had initial low serum vitamin B12 levels, but only two had definite B12 deficiency on further evaluation. Three patients who had initially low B12 levels had normal levels subsequently during outpatient follow up. When low serum vitamin B12 levels are discovered in psychiatric patients without hematologic or neurologic findings, a diagnosis of B12 deficiency should not be presumed without further evaluation. Key words: screening: psychiatric patients; vitamin B12. PMID- 7996298 TI - Anticoagulation therapy and primary care internal medicine: a nurse practitioner model for combined clinical science. AB - The anticoagulation clinics at the University of Virginia Health Sciences Center and the University of California at Davis Medical Center are nurse-practitioner operated, are affiliated with the general medicine clinic, and rely on portable prothrombin time (PT) monitors that use whole blood and provide timely as well as accurate results reported in PT seconds or as the international normalized ratio (INR). On-site PT/INR testing at these clinics simplifies anticoagulation, mandates direct patient contact, and facilitates primary as well as comprehensive care for patients requiring multispecialty services in large tertiary care centers. Encounters are relatively brief, averaging 19 minutes; 72% of the encounter time involves anticoagulation care and 28% involves primary care. Anticoagulation results using portable PT/INR monitors are safe and accurate based on comparisons with results from clinics relying on standard instruments. PMID- 7996301 TI - Cost-effectiveness in pedal osteomyelitis. PMID- 7996299 TI - Clostridium difficile infection: a common clinical problem for the general internist. AB - Considering the current wide use of antimicrobial agents, the general internist is commonly faced with the patient at risk for diarrhea due to C. difficile. The diagnosis should be considered for any patient with diarrhea who has received any type of antibiotic therapy in the preceding 4-6 weeks. Symptoms may range from a minor bout of diarrhea to fulminant and fatal colitis. Diagnosis usually requires demonstration of the toxin in stool; culture of the organism and fiberoptic endoscopy may play an adjunctive role in selected clinical settings. The ultimate goal in the treatment for C. difficile infection is to repopulate the normal colonic flora in the most efficacious manner. Minimally symptomatic patients may respond to discontinuing the offending antimicrobial agent or using nonspecific binding agents. Oral vancomycin continues to be the "gold standard" for specific treatment, while metronidazole therapy is considered the first-line agent for individuals with milder infection. Oral bacitracin shows promise, though large studies are lacking. Patients with multiple relapses of C. difficile diarrhea can be treated with prolonged courses of vancomycin or a combination of vancomycin and rifampin. Intensive care unit patients who are NPO have few therapeutic options besides intravenous administration of metronidazole and oral administration of vancomycin via clamped nasogastric tube. Preventive efforts are directed at cautious use of antibiotics and the use of vinyl gloves when caring for patients with known infection. PMID- 7996300 TI - Anxious and depressed patients in primary care: the need for more clinical epidemiology. PMID- 7996302 TI - Primary care needs. PMID- 7996303 TI - Family planning for healthy nations. PMID- 7996304 TI - Breastfeeding technique. PMID- 7996305 TI - Breastfeeding technique. PMID- 7996306 TI - RU 486: an alternative to surgical abortion. AB - After 5 years of use in more than 100,000 European women, RU 486, an antiprogestin medication used as a medical abortifacient, has recently come under scrutiny in the United States. This article discusses the current and potential uses of RU 486. Also addressed are the history, advantages, and disadvantages of medical abortion (including the acceptability of the method from a woman-centered perspective); new clinical trials; and ethical issues. PMID- 7996307 TI - Uses of GnRH agonists. AB - Gonadotropin-releasing hormone agonists are a relatively new class of drugs, which, when chronically administered, result in marked reductions in blood levels of testosterone and estrogen. These drugs include leuprolide acetate (Lupron); the first GnRH agonist to be approved in the United States, nafarelin acetate (Synarel); and goserelin acetate (Zoladex). Approved indications for these drugs, depending on the specific agent, include advanced prostate cancer, endometriosis, and precocious puberty. These and other investigational GnRH agonists are also being evaluated in many other diseases, including uterine fibroids, polycystic ovarian disease, breast cancer, fibrocystic breast disease, benign prostatic hypertrophy, and irritable bowel syndrome. Because of their therapeutic potential in many endocrinologic disorders, the GnRH agonists represent one of the most important advances in hormonal therapy in the past few decades. Thus, it appears likely that in the 1990s a greater number of patients will be receiving these agents. This article summarizes the application of GnRH agonist drugs in clinical practice, their side effects, and important information for patient use. PMID- 7996308 TI - Amnioinfusion: an update. AB - Amnioinfusion is one of the most innovative techniques of the decade. The authors reviewed current literature, research indications, and nursing implications for amnioinfusion. Current technology has simplified the amnioinfusion procedure. This technique provides both therapeutic and prophylactic regimens for the intrapartum mother and her fetus, and it has many clinical implications for nursing. PMID- 7996309 TI - Infant stimulation: modification of an intervention based on physiologic and behavioral cues. AB - Research involving developmental intervention with premature infants in the hospital has traditionally taken two paths: application of a sensory stimulation protocol and individualized assessment and treatment. This article describes a new method that combines some of the philosophical strengths of these two approaches. A decision tree is presented to standardize the modifications of a developmental intervention based on physiologic and behavioral cues. PMID- 7996310 TI - Gender differences and perceptions about childbearing among infertile couples. AB - OBJECTIVE: To explore gender differences and responses of infertile couples to childbearing issues. DESIGN: Data analysis from the first wave of a larger three wave prospective panel study. Face-to-face interviews with both husbands and wives were conducted. SETTING: Husbands and wives were interviewed separately in their homes. One was generally interviewed immediately after the other. PARTICIPANTS: One hundred sixty-one infertile couples in southeastern Michigan were interviewed in 1988. MEASURES: Variables of interest included the self recognized source of the fertility problem, the importance of children to individuals, stress associated with infertility treatment, the number of tests and treatments received, the acceptability of indicated treatments, the length of time couples expected it would take to have a child, and the ideal and expected number of children. RESULTS: Women experienced significantly more stress from tests and treatment, placed greater importance on having children, were more accepting of indicated treatments, and wanted more children than men did. CONCLUSIONS: Implications for nurses working with infertile couples are discussed, including provision of emotional support, evaluation of perceptions of success, assessment of couples' expectations, and inclusion of husbands in decision making. PMID- 7996311 TI - Changes in maternity care and the impact on nurses and nursing practice. AB - OBJECTIVE: To determine changes maternity nurses have experienced and the impact these changes have had on nursing practice. DESIGN: Descriptive survey using a randomized sample. PARTICIPANTS: Four hundred fifty-one inpatient female maternity nurses. MAIN OUTCOME MEASURES: Changes in maternity care, impact of the changes on nursing practice, and personal and professional perceptions and activities before and after the changes. RESULTS: Reported changes were use of technology, legal climate, shorter patient stay, cost containment, inclusion of family, cross training, consumer demand, and single-room maternity care. Inclusion of the family, technology, and single-room care were rated highly for worth and improvement in quality of care. Though described as challenging and rewarding, change was an energy drain. Change was often seen as a result of administrative mandate. CONCLUSIONS: Perceptions of change vary, but no change is easy to implement. Opportunities for staff input, administrative support, and adequate time and staffing levels during change facilitate adjustment. PMID- 7996312 TI - Substance abuse among inner-city Hispanic women: exploring resiliency. AB - OBJECTIVE: To identify factors that prevent drug abuse among young Hispanic women living in inner cities and to acquire ideas for preventive strategies. DESIGN: Qualitative interviews of focus group participants to explore perceptions about drug use. SETTING: An urban location adjacent to a neighborhood health clinic. PARTICIPANTS: Twenty-four young Hispanic women recruited from an inner-city prenatal clinic. MAIN OUTCOME MEASURES: Identification of themes that trigger or deter drug use. Acquisition of preliminary knowledge required for further development of data collection instruments and design of interventions for use with inner-city Hispanic women. RESULTS: Identified six themes through qualitative data analysis of interview narratives. CONCLUSIONS: Compared themes with existing theoretical models and described implications for nursing practice. PMID- 7996313 TI - Androgenic/anabolic steroid-induced intrahepatic cholestasis: a review with four additional case reports. AB - Four cases of severe cholestasis attributed to anabolic/androgenic steroid usage are reported. These cases are reported because each was severely jaundiced (peak bilirubin level 62 mg/dl), developed advanced hepatic failure (Child's Class B) and was referred to a liver transplant center for consideration for liver transplantation. The hepatic dysfunction and cholestasis in each persisted for 3 months or more. Moreover, in two the hepatic dysfunction was complicated by the development of renal dysfunction and anemia requiring additional medical interventions. With prolonged medical therapy, each case recovered fully without transplantation. These cases are important because they demonstrate that drug induced cholestasis can be prolonged, can mimic advanced liver disease, and can be associated with co-existent renal dysfunction. PMID- 7996314 TI - Autologous bone marrow transplantation for metastatic breast cancer. AB - Metastatic breast cancer accounts for 18% of cancer deaths among women in the U.S. Conventional combination chemotherapy produces responses in 50% to 80% of women with metastatic breast cancer, but is never curative. A major medical center administered high-dose chemotherapy and autologous bone marrow transplantation to 68 women with metastatic breast cancer between 1983 and 1993. Forty-nine of these women had estrogen receptor-negative tumors, a poor prognostic sign. Eighteen women with estrogen receptor-positive tumors had failed prior hormonal manipulation or had metastatic breast cancer at initial diagnosis. Prior to transplantation, 37 women were in first complete or partial remission, 8 were in their second complete or partial remission, 4 had stable disease, 14 had progressive disease, and 5 were in untreated relapse. Bone marrow transplantation preparatory regimens included high doses of single agents or combination chemotherapy. Among women not in remission before transplantation, 71% entered a partial or complete remission following transplantation. Overall, 29 women (43%) were in complete remission after marrow transplantation. Twelve women (18% overall) remain free of disease between 2 and 73+ months post-ABMT. Those in first complete or partial remission prior to transplant (37 patients) had a higher response rate (86%) and higher complete responses (62%), and 10 (27%) are free of disease. There were nine treatment-related deaths (13%). Forty-seven patients (69%) have died from breast cancer following autologous transplantation. Relapses occurred primarily at sites of previous disease. All relapses have occurred within 22 months of ABMT. CONCLUSION: Autologous bone marrow transplantation for metastatic breast cancer in first complete or partial remission has produced a 27% disease-free survival. This therapy should be considered for selected patients with metastatic breast cancer. PMID- 7996315 TI - Understanding mechanical ventilation: patient monitoring, complications, and weaning. AB - Mechanical ventilation can provide life saving support to critically ill patients with respiratory failure. The implementation of appropriate monitoring techniques and an awareness of potential complications can increase the safety of mechanical ventilation. Several efficacious weaning methods can be utilized and none is clearly superior to the others. The improper use of any weaning technique can result in respiratory muscle fatigue delaying extubation. Determining patient suitability for extubation is an inexact science. The physical examination during a spontaneous breathing trial and the use of the rapid shallow breathing index can assist the clinician in the difficult decision as to the timing of extubation. PMID- 7996316 TI - Vaginal hysterectomy: the use of a self-retaining retractor. AB - This report concerns the indications, technique, and safety of vaginal hysterectomy among 213 women. It further examines the comparative risks of complications and costs between 107 patients whose operations were performed with the use of the new retractor during the 5-year period ended June 1991 and 106 other patients whose surgeries were done during 4 preceding years when the retractor was not available. The selected characteristics of the patients undergoing vaginal hysterectomy in the two groups were largely similar. When the retractor was used, suturing the cuff and pedicles was easier, as the retractor facilitated good exposure and better visibility. In no case was there any injury or the need for transfusion. Of 7 patients with morbidity, 1 had no demonstrable cause, 3 had urinary tract infection, and 3 had cuff cellulitis of which one progressed into abscess requiring transvaginal drainage 6 days postoperation. My experience with 107 vaginal hysterectomies using the self-retaining retractor demonstrates that the retractor was instrumental in significantly reducing operative time, blood loss, and morbidity. PMID- 7996317 TI - Our rate of drowning deaths is 25% above the national average. PMID- 7996318 TI - A prospective comparative study of the compression hip screw and the gamma nail. AB - Achieving bony union and early weight bearing in peritrochanteric femur fractures poses a continuous challenge for the orthopedic surgeon. Current standards of surgical fixation for the myriad possible fracture patterns include the compression hip screw (CHS), the 90 degrees/95 degrees blade plate, and locked intramedullary nails. The gamma nail (GN) was designed as a "hybrid" of these devices, combining theoretical biomechanical advantages that should allow earlier postoperative weight bearing with surgical technique advantages that should decrease operative morbidity. Because these theoretical advantages were unproven in a clinical setting, we prospectively randomized 75 consecutive patients with peritrochanteric femur fractures into two groups to examine the fixation of these fractures with the GN as compared to the CHS. We found no significant differences in preoperative or intraoperative parameters. Postoperatively, the subtrochanteric fracture group treated with the GN achieved earlier weightbearing status, although this was not statistically significant. 72 patients were available for follow-up at a minimum of 6 months. All fractures had clinically and radiographically healed, and 94% of the patients continued to be ambulatory. Major complications included missed distal locking screws (one patient), cutting out of the lag screw superiorly in the femoral head (two patients), and a femur fracture at the distal end of the GN (one patient). In our series, the GN produced clinical results commensurate with current standards of fixation for peritrochanteric femur fractures. Although the GN allowed earlier independent weightbearing status in patients with subtrochanteric fractures, the procedure was technically more demanding and had a significant learning curve. PMID- 7996320 TI - Distribution of clindamycin in cortical bone during direct local infusion of the canine tibia. AB - The distribution of clindamycin in tibial cortical bone, administered via direct local infusion with an implantable pump, is described. Clindamycin concentrations in cortical bone were measured after 3, 7, and 21 days of intraosseous infusion. The tibia were divided into four quadrants relative to the outflow infusion catheter site located in the medial aspect of the mid-diaphysis. A gradient of 5 30 mm from the infusion site was documented in all four quadrants (proximal lateral, proximal medial, distal lateral, and distal medial). At all sampling times, clindamycin concentrations in all quadrants exceeded the minimum inhibitory concentrations for gram-positive aerobic bacteria, including Staphylococcus aureus and S. epidermidis, and both the gram-positive and gram negative anaerobes, including Peptostreptococcus species and Bacteroides species. The data suggest that gravitational forces affect the diffusion of the clindamycin because concentrations in both distal quadrants were greater than in corresponding proximal quadrants. PMID- 7996319 TI - Cortical bone blood flow in reamed and unreamed locked intramedullary nailing: a fractured tibia model in sheep. AB - We compared the effects of reamed versus unreamed locked intramedullary nailing on cortical bone blood flow in a fractured sheep tibia model. A standardized spiral fracture was created by three-point bending with torsion, and each tibia was stabilized by insertion of a locked intramedullary nail. Eleven animals were randomized into two groups: one that had reaming before nail insertion and one that did not. Blood flow was measured in real time using laser Doppler flowmetry. Cortical bone perfusion measurements were made at three locations (proximal diaphysis, fracture site, distal diaphysis) and at eight time intervals (prefracture, postfracture, postreaming, postnail insertion, postlocking, and at 2-, 6-, and 12-week follow-up). All animals were killed at 12 weeks postoperatively. After reamed nail insertion, cortical bone perfusion was significantly decreased (p < 0.0009). After unreamed nail insertion, perfusion was decreased less (p < 0.003). Insertion of locking screws did not affect blood flow. Cortical bone perfusion was greater in the unreamed group at completion of the procedure (p < 0.011), at 2-week follow-up (p < 0.006) and at 6-week follow up (p < 0.027). The findings suggest that cortical revascularization had occurred by 6 weeks in the unreamed group but not until 12 weeks in the reamed group. The study demonstrates that cortical circulation is spared to a greater degree by unreamed nailing. This may be advantageous in severe open tibial fractures where blood supply is already significantly compromised. PMID- 7996321 TI - The efficacy of various irrigation solutions in removing slime-producing Staphylococcus. AB - To determine which type of irrigation solution and which method of irrigation most effectively removes slime-producing Staphylococcus from implant surfaces, we performed experimental washings of bacteria-coated stainless steel screws with various solutions delivered by bulb syringe or by jet lavage. The quantity of bacteria remaining on the screw surface was determined after irrigation with 1 L of saline, 1 L of antibiotic solutions, or 1 L of saline containing a liquid soap. Antibiotic solutions tested included bacitracin, neomycin, and polymyxin/neomycin. We found that the use of power irrigation increased the removal of bacteria by a factor of at least 100 over bulb syringe irrigation of the same volume, no matter which solution was used. This effect ranged from a 100 fold improvement for neomycin, to a 285-fold effect for the polymyxin solution. The addition of antibiotic drugs to the irrigation solution had no significant effect on bacterial removal, and none of the antibiotic solutions were statistically different from saline alone in the amount of bacteria removed from the screws. The addition of a liquid soap solution dramatically increased the amount of bacteria removed by irrigation, reducing the residual bacteria per screw from a colony count of 3.5 x 10(4) for polymyxin (the best of the antibiotic solutions), to 4.38 x 10(3). This difference was statistically significant as judged by Student's t test, with p = 0.01. We have concluded that the use of power irrigation improves the ability to clean this pathogenic bacteria from metallic surfaces, and that the addition of antibiotic drugs to the irrigation solution does not.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7996323 TI - The reliability of detecting screw penetration of the acetabulum by intraoperative auscultation. AB - Open reduction and internal fixation of the acetabulum frequently requires placement of screws in a blind fashion that risks penetrating the joint surface. While in the operative suite, direct visualization of the joint surface may not be possible, and fluoroscopy can be difficult to interpret. Auscultation of the hip with motion in a quiet room has been suggested as a useful adjunct to detecting screw penetration. Carrying that concept further, we auscultate the hip using a sterile esophageal stethoscope at the operating table and have found this to be a highly reliable method of detecting intraarticular screw placement. To test the reliability and reproducibility of this technique, an experiment was performed using inexperienced volunteers. In part I, two adult mongrel dogs were prepared. A screw was placed violating the hip joint in one dog, and in the other dog a screw was placed near but not penetrating the joint. Screw placement was verified under direct vision. Seventy-seven volunteers who did not know which hip was penetrated then auscultated both hips in random order and recorded their impressions after each hip was heard. After hearing both hips, 74 of 77 were able to identify the screw in the hip joint correctly; 69 were able to recognize the extraarticular screw correctly. In part II, both hips of a human cadaver were exposed and dislocated. In one hip, a screw was placed that tangentially violated the joint, and in the same area of the contralateral hip a screw was placed that did not penetrate the joint surface.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7996322 TI - Acetabular fractures: long-term follow-up of open reduction and internal fixation. AB - Eight-seven acetabular fractures in eighty-seven patients underwent open reduction and internal fixation at Vanderbilt University Hospital from 1984 to 1989. Fifty-six were treated by orthopaedic traumatologists. Fifty-six patients returned for long-term follow-up (range 24-80 months, average 43). Harris hip ratings were used to clinically grade the results. Poor results were found in 43%. Eighty-three percent of the patients with poor results had satisfactory surgical reductions with < 3 mm of residual displacement. Factors other than surgical reduction contributed significantly to the poor results. These included hip dislocation associated with the fracture, class III or IV heterotopic ossification, development of avascular necrosis, and age > 40 years. These factors in addition to adequacy of surgical reduction allow us to better counsel patients as to long-term prognosis. PMID- 7996324 TI - Extramedullary skeletal traction for intramedullary femoral nailing. AB - The through-and-through forms of femoral skeletal traction that are often used during intramedullary nailing for femur fractures can present two problems: (a) impingement with the intramedullary nail, requiring repositioning of the traction pin intraoperatively under radiographic control, to a position that may not optimally control the fracture; and (b) the risk of contaminating the intramedullary canal that will soon contain the metallic fixation device, especially when placed in the emergency room or at the bedside. Two new forms of extramedullary skeletal femoral traction are presented. The pullout strength and optimal positioning of these devices on the distal femur were evaluated. The first form of extramedullary traction evaluated was the large AO/ASIF pinless clamp. The second form of extramedullary traction, the extramedullary skeletal clamp, was based on a modification of the Gardner-Wells tong. These two forms of skeletal traction were compared with standard tensioned Kirschner wire (K-wire) through-and-through traction. Six fresh-frozen distal femora from donors (average age 29 years) were used to test the three femoral traction devices. Five of these specimens were skeletally mature. A total of 38 pullout tests were conducted. The pullout strength of the tested devices was in the following descending order: (a) tensioned K-wire; (b) extramedullary skeletal clamp (in the optimal metadiaphyseal position, 77% the strength of the K-wire); and (c) large ASIF pinless clamp (in the optimal metaphyseal position, 46% the strength of the K wire). The mode of failure for each device was cut out through or from the bone.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7996325 TI - Comparison of torsional strength of humeral intramedullary nailing: a cadaveric study. AB - Control of rotation after intramedullary fixation of the humeral shaft has been observed to vary clinically. Two of the newer intramedullary nails specifically designed for the humerus were tested. Transverse and spiral fractures were created in 35 fresh-frozen cadaveric humeri. The constructs were tested in a materials testing system to evaluate in vitro the torsional strength of the nailed humeral fractures. Intact bones showed a mean peak torque of 53 +/- 17 Nm. The humeri fixed with the Russell-Taylor nail (n = 18) using one interlocking screw proximally and one distally showed a mean torsional strength of 10.4 +/- 3.6 Nm. The specimens fixed with the Seidel nail (n = 17), interlocked proximally with two screws and distally by the friction of three expanded flanges against the inner cortex, had a significantly lower mean torsional strength of 1.5 +/- 0.6 Nm (p < 0.0005). When compared with intact bones, constructs using the Russell-Taylor nail achieved 20% of mean peak torque. This improved rotational strength should permit an earlier return to full functional use of the extremity. PMID- 7996326 TI - Fatigue testing of cerclage stainless steel wire fixation. AB - Because wire fixation continues to be used extensively in the practice of orthopaedic surgery, despite a high incidence of wire breakage, understanding the mechanism of this failure is of important clinical interest. The aim of this study was to investigate the failure of cerclage stainless steel wire using an in vitro cyclic loading device. A stainless steel testing fixture consisting of two half cylinders with a combined diameter of 2.5 cm was mounted in a servo hydraulic testing machine. Specimens of number 18 gauge (0.97 mm diameter) and number 16 gauge (1.22 mm diameter) 316L stainless steel wire were mounted around the two half cylinders in a cerclage manner using three different fastening methods: a uniform symmetrical twist, a knot twist, and a square knot. Single load-to-failure and cyclic load tests were performed under controlled tensile displacement. The cerclage wire system fastened with a twist resulted in failure at loads significantly lower than systems fastened with the knot twist and the square knot. Cyclic loading of the wire fastened with twists also showed decreased fatigue properties when compared to those fastened with the knot twist and the square knot. In all tests, the 16-gauge wire was found to be clearly superior to the 18-gauge wire. For both wires, fatigue strengths at 100,000 cycles were only 30-37% of the static ultimate strength. These results show that wire diameter and fastening system are two important factors affecting the mechanical properties of the resulting fixation. PMID- 7996327 TI - Concomitant rotator cuff tear and brachial plexus injury in association with anterior shoulder dislocation: unhappy triad of the shoulder. AB - High incidences of nerve lesions or rotator cuff tears in association with shoulder dislocations have been reported. However, the simultaneous occurrence of these three lesions has only been reported once previously. This case is an example of a not so uncommon injury, which emphasizes the importance of looking for associated brachial plexus and rotator cuff lesions when examining a patient with shoulder dislocation. PMID- 7996328 TI - Ipsilateral Monteggia equivalent injury and distal radial and ulnar fracture in a child. AB - A rare, previously undescribed combination of ipsilateral type III Monteggia equivalent and distal radial and ulnar fracture in a child is reported. A good result was obtained by nonoperative treatment. PMID- 7996329 TI - Transradial styloid, transtriquetral perilunate dislocation of the carpus with an associated fracture of the ulnar border of the distal radius. AB - A rare case of transradial styloid, transtriquetral perilunate dislocation associated with an ulnar border fracture of the distal radius is described. The mechanism of injury is discussed, and the results of treatment are reported. PMID- 7996330 TI - Osteochondroma formation after a Salter II fracture. AB - Osteochondromas are one of the most commonly observed benign bone tumors. Although there have been a number of experimental studies carried out to determine the origin of osteochondromas, their etiology remains a controversial issue. A well-documented case is presented in which a displaced Salter-Harris type II physeal fracture preceded the development of an osteochondroma. PMID- 7996331 TI - Cystic degeneration and calcification of muscle: late sequelae of compartment syndrome. AB - Cystic degeneration and calcification of the leg are uncommon late sequelae of compartment syndrome. Previously reported cases have all involved the anterior compartment of the leg. We present a 68-year-old man with a mass in the superficial posterior compartment of the leg who presented 37 years after the initial trauma and ischemic myonecrosis. MRI was useful in establishing the diagnosis and early surgical intervention. The mass was excised and closed primarily over a drain. Patient was followed up for 29 months, and there were no secondary infections, chronic sinus formation, or recurrences. Based on our experience and the available literature review, we recommend considering either excision and primary closure, or repeated needle aspiration of the mass. Packing the wound and delayed closure may lead to secondary infection, chronic sinus formation, and lower limb amputation as potential complications. PMID- 7996332 TI - Treatment of compartmental liquefaction as a late sequelae of a lower limb compartment syndrome. AB - Symptomatic liquefaction and calcification of muscle tissue as a late sequela of compartment syndrome of the lower leg is rare. The literature shows a high complication rate involved with simple debridement of these compartments. In our limited experience, complete compartmental debridement and immediate introduction of functional viable muscle may prevent the documented complications of chronic drainage and infection. PMID- 7996333 TI - Anterolateral subluxation of the talus after overlooked dislocation of the tibialis posterior tendon. AB - We report a case of tibialis posterior tendon dislocation into the disrupted ankle mortise between the tibia and fibula that was overlooked in the initial operative treatment of a fracture dislocation of the ankle with syndesmosis disruption. Recurrent widening of the ankle mortise prompted revision surgery where the posterior tibialis tendon dislocation was discovered to be the cause of secondary joint subluxation. The course of the tendon was corrected and the anatomy of the joint restored. One year after revision there is a good clinical result, however early posttraumatic osteoarthritis of the tibiotalar joint is seen radiologically. PMID- 7996334 TI - Reflections on the Michigan occlusal splint. AB - Specific features related to the development, design and use of the Michigan splint have been described. Additional benefits from the Michigan splint beyond what can be expected from conventional stabilization splints and bite planes have been suggested. Important aspects of corrections and maintenance care of the Michigan splint have been stressed. PMID- 7996335 TI - Multidimensional evaluation of craniomandibular dysfunction. I: Symptoms and correlates. AB - To standardize clinical history taking, a comprehensive anamnestic questionnaire was developed (Screen). Screen includes questions about (i) pain, (ii) other symptoms of CMD, (iii) correlates of CMD, (iv) psychosocial factors, and (v) general health. Variables discriminating between subgroups of clinical cases and controls were described successively. This study was performed to assess whether subgroups of patients with signs and symptoms of craniomandibular dysfunction (CMD), and a control group of dental patients with and without signs and symptoms of CMD, can be characterized by differential report of signs and symptoms of CMD, as reported in Screen. Results indicate that Screen can be used to discriminate between (i) subgroups of subjects with signs or symptoms of CMD (both clinical cases and controls) and controls without signs or symptoms of CMD; (ii) subgroups of clinical cases and controls with signs and/or symptoms of CMD; and (iii) patients with CMD with mainly a myogenous component and patients with CMD with mainly an arthrogenous component. Differences between patients and controls are interpreted with regard to the correct classification of patients with CMD with mainly a myogenous component and patients with CMD with mainly an arthrogenous component, and with regard to the subjective treatment need for CMD. The results of logistic regression analyses indicate that subsets of items of Screen correctly classified up to 80% of patients with myogenous or arthrogenous CMD. Implications for further research were discussed. PMID- 7996337 TI - Thermocycling--the effects upon the compressive strength and abrasion resistance of three composite resins. AB - The purpose of this investigation was to examine the effects of thermocycling upon the compressive strength and abrasive wear resistance of three commercial composites Fulfil, P-50 and Herculite-XR. Specimens of each material were divided into five treatment groups comprising a control, and four different cycling and storage regimes. Tests for compressive strength and wear resistance were carried out. Prior to testing all specimens were stored in distilled water for 1 week. Three groups were stored at a temperature of 37 degrees C and the remaining two at 60 degrees C. Thereafter all groups that were thermocycled were subjected to 750 cycles of a thermocycling regime consisting of the cycle ACAB where A and B represent the fixed temperatures of 37 degrees C and 5 degrees C, and C, depending upon the treatment group, either 50 degrees C or 60 degrees C. One-way analyses of variance upon the compressive strength and wear factor data following the treatments highlighted significant differences in the mean compressive strength for all materials (Fulfil (P < 0.05), P-50 and Herculite-XR (P < 0.01)) and in the wear factor values for only Fulfil and P-50 (P < 0.001). Surprisingly, thermocycling P-50 with an upper temperature limit of 50 degrees C had catastrophic consequences upon the measured properties. It is concluded that some of the observed behaviour may have potentially detrimental consequences upon the long-term clinical durability of the materials tested. PMID- 7996336 TI - Multidimensional evaluation of craniomandibular dysfunction. II: Pain assessment. AB - To standardize clinical history taking, a comprehensive anamnestic questionnaire was developed (Screen). Screen includes questions about: (i) pain, (ii) other symptoms of craniomandibular dysfunction (CMD), (iii) correlates of CMD, (iv) psychosocial factors, and (v) general health. The current study focuses on variables in Screen concerning pain reported somewhere in the head, neck and/or shoulders. This study was performed to assess whether subgroups of patients with signs and symptoms of CMD and a control group of dental patients with and without signs and symptoms of CMD can be characterized by differences in areas reported to be painful, in quantitative and qualitative characteristics of pain, and in factors exacerbating pain. Results indicate that several characteristics of pain as measured in Screen can be used to discriminate between: (i) subgroups of subjects with signs and/or symptoms of CMD and controls without signs or symptoms of CMD, (ii) subgroups of clinical cases and controls with signs or symptoms of CMD, and (iii) patients with CMD with mainly a myogenous component and patients with CMD with mainly an arthrogenous component. The results of logistic regression analysis indicate that four adverbs describing pain correctly classified 75% of patients with CMD-myo and patients with CMD-arthro. Differences between patients and controls are interpreted with regard to the correct classification of patients with CMD with a mainly myogenous component and patients with CMD with a mainly arthrogenous component and the subjective treatment need for CMD. Implications for further research are discussed. PMID- 7996338 TI - Assessment of chewing efficiency: a comparison of particle size distribution determined using optical scanning and sieving of almonds. AB - Particle sizes obtained with progressive chewing cycles were quantified by use of an optical scanning device and compared with the sieving method. The aim of this study was to validate the optical method by comparison with sieving using a natural test food, almond. Masticatory efficiency was assessed in six dentate subjects. The almonds were chewed for 1, 4, 8, 16 and 32 chewing strokes. Each experiment was replicated. The chewed material was sieved through a 1 mm aperture sieve on a Buchner funnel and dried after washing with water and 100% alcohol. The dried particles were weighed and scanned by an optical scanning device for number and size. The same samples were sieved and weighed with a conventional sieve method. The results of both methods were described by particle size distributions based on the volume of particles. The results derived from the optical scanning and sieving showed similarity. It can be concluded that the optical method is simple to use, faster than sieving and needs little skill in the use of equipment. The comparison of the results validates both methods. PMID- 7996339 TI - Mercury vapour suppression by various liquid media. AB - Fresh and used photographic fixer, Merconvap and water were evaluated for their ability to suppress the vapourization of mercury. Mercury vapour concentration above the four test storage liquids was measured at various times between 10 min and 335 days, using a mercury vapour measuring instrument. The data were analysed using a Student-Newman-Keuls multiple comparison test (P = 0.05). The results showed that fresh and used fixer and Merconvap suppressed the vapourization of mercury to below the detection limit of the measuring instrument (0.01 mg/m3). Water was much less effective compared with the other liquids and showed an increase in mercury vapour concentration with log t. PMID- 7996340 TI - Correlation between autoregressive moving-average model parameters of electromyogram of human jaw closing muscles and maximum clenching time at intercuspal position. AB - During maximum clenching in the intercuspal position, surface electromyograms of left masseter and anterior temporal muscles were sampled in 16 healthy subjects with natural dentitions to establish a four-order, autoregressive (AR) moving average (MA) model of the myoelectrical signals. The correlation coefficients and the linear regression between the model parameters and the clenching time were calculated. The model parameters had the positive or the negative correlation, and AR model parameters had the higher correlation than MA model parameters. The model parameters relate to muscular fatigue and the slope of the regressive equation relates to the endurance time of the isometric contraction. PMID- 7996341 TI - Leaching from glass ionomer cements. AB - This study compared the electrical conductivities, pH and leached ion (F-, Ca, Al, Si) concentrations in supernatant liquids obtained from four glassionomer cements, a buffered ionomer cement, a polycarboxylate cement and a zinc phosphate cement, at three different levels of settings. The result indicated that the measured parameters are highest for the unset condition of cements and decreases as the set condition is approached, except for pH, which shows the opposite trend. Two pulp sensitive glassionomer cements, Chem Bond and Ketac Cem showed high Ca:F ratios as well as high Ca and F concentrations. Further, it is suggested that the cytotoxicity of leached F-, Si, Al and Zn at high concentration and at low pH may induce sensitivity in tooth structure. PMID- 7996342 TI - Growth and/or acid production of Candida albicans on soft lining materials in vitro. AB - Effects of soft lining materials on the growth and/or acid production of Candida albicans were investigated using a simplified method monitoring the pH change in the growth medium. Reverse sigmoidal pH curves were observed with all samples and, as compared with acrylic, all soft lining materials inhibited fungal growth or acid production in the following way, i.e. delay of the beginning of a rapid and linear decline in pH, decreases in the rate of linear change in pH and increases in minimum pH. Further examinations using a surface-modified glass tube revealed that the order of Candida growth agreed with the relative hydrophobicity and adherence capacity of substrates, suggesting that this adherence capacity affected the yeast growth on their surfaces. Besides adherence capacities of substrates, the powder, liquid and plasticizer of some soft lining materials directly inhibited Candida growth. Thus, the results obtained here revealed that several factors within soft lining materials affected Candida growth and/or acid production. PMID- 7996343 TI - Mandibular advancement with dental appliances in obstructive sleep apnoea. AB - The purpose of this study was to compare the effects of a modified Herbst appliance (mHA) and a muscle relaxation appliance (MR) on nocturnal breathing and body movement activity in patients with obstructive sleep apnoea syndrome (OSAS). To increase the airway space posterior to the tongue base without severely affecting the craniomandibular joint, the mHA was adjusted to anchor the mandible at 50% of maximum protrusion. MR producing an occlusal coverage but no protrusion served as a control appliance. All-night static charge-sensitive bed (SCSB) and finger oximeter recordings were done to six male patients in three conditions: first without dental device and then with mHA and with MR, in a random order, after a 2 month period of habituation. The oxyhaemoglobin desaturation events were 44.7 h-1 of recording observed during the control night, 29.6 h-1 with mHA (P = 0.087). The frequency of body movements decreased from 34.9 to 20.4 h-1 (P = 0.0079), respectively. MR had no significant effects either on the frequency of the desaturation events or the frequency of body movements, but the increased respiratory resistance breathing, indicating presence of partial upper airway obstruction, was reduced from 14.3 to 6.9% of the time in bed (P = 0.022). We conclude that 50% protrusion chosen for these experiments, produced with a mHA, brought about some alleviation of upper airway obstruction in our preselected patients, but did not lead to sufficient control of apnoea. The reduction of partial upper airway obstruction induced with a MR warrants further studies in a larger patient population. PMID- 7996344 TI - Variations in oral temperature. AB - This study investigated the temperature of healthy oral mucosa and underlying bone. Using a fine thermocouple and digital thermometer, four groups of temperatures were measured: (i) adjacent to unerupted third molars before and after surgical removal (n = 51); (ii) at the same site in patients not undergoing surgery (n = 30); and (iii) at the buccal incisor mucosa (n = 30). In each group sublingual temperatures were measured in order to calculate the temperature differential between measurement site and sublingual temperature to compensate for variations between sites and individuals. In the final group (iv) (n = 10) sublingual temperature was recorded in a closed mouth. Mean alveolar bone temperature was 5 degrees C cooler than overlying mucosa, and mean post-operative mucosal temperature was some 2.5 degrees C cooler than before operation (t = 2.32, P < 0.001). Sublingual temperature, in a closed mouth, remained relatively constant. In an open mouth, in both anterior and posterior regions, there were statistically significant decreases in sublingual temperature and in mucosal temperature differentials. Significant differences were also found between temperature differentials calculated using sublingual temperature measured at baseline and after 10 min. This indicates that sublingual temperature should be measured just prior to measuring a mucosal site. PMID- 7996345 TI - Effect of unilateral bite splint on mastication in the miniature pig. AB - Unilateral premature occlusal contacts are known to alter masticatory activity levels during clenching, but whether natural chewing is similarly affected is not known. The purpose of this study was to analyse the effects of a unilateral bite splint on mastication. Eleven experiments were carried out using three miniature pigs. Electromyography of the masticatory muscles and movements of the jaw were recorded during natural chewing before and after inserting a bite splint on the second and third deciduous premolars. In contrast to human clenching, the integrated activities of the jaw-closing muscles increased, especially on the contralateral side. The increases were mainly due to the prolongation of the burst durations. Jaw opening activity was increased as well. The frequency of mastication fell slightly and the animal preferred to chew food on the bite splint side. These results demonstrate the importance within the particular experimental conditions of the occlusal condition in regulating chewing behaviour. PMID- 7996346 TI - Acute immune thrombocytopenic purpura: a comparative study of very high oral doses of methylprednisolone and intravenously administered immune globulin. AB - We compared very high doses of methylprednisolone with intravenously administered immune globulin for treatment of acute idiopathic thrombocytopenic purpura. Fifty seven children were randomly assigned to receive the immune globulin preparation, 0.5 gm/kg per day for 5 consecutive days (n = 19), orally administered methylprednisolone, 30 mg/kg per day for 7 days (n = 19), or orally administered methylprednisolone, 50 mg/kg per day for 7 days (n = 19). There were no differences in the response of the platelet counts among the groups. We conclude that these two therapies were equally effective; choice between them may be made according to cost and therapy-related risks. PMID- 7996347 TI - Edwards A. Park. PMID- 7996348 TI - Effect of race on lipoprotein profile. PMID- 7996349 TI - Genetic risk factors for melanoma in children. PMID- 7996351 TI - Pneumococcal bacteremia and diarrhea. PMID- 7996350 TI - Oral antibiotic therapy for suspected occult bacteremia. PMID- 7996352 TI - Nephrotic syndrome as the initial manifestation of acquired immunodeficiency syndrome. PMID- 7996353 TI - Cardiomyopathy with congenital adrenal hyperplasia. PMID- 7996354 TI - Relation of percentage of body fat and maximal aerobic capacity to risk factors for atherosclerosis and diabetes in black and white seven- to eleven-year-old children. AB - OBJECTIVE: To determine whether body fatness, aerobic capacity, and fat distribution are associated with levels of cardiovascular risk factors in children. METHODS: Subjects (N = 57) were 7 to 11 years of age; their percentage of body fat ranged from 10% to 58%. The percentage of fat was measured with dual energy x-ray absorptiometry, maximal aerobic capacity was measured on a treadmill, fat distribution was expressed as the waist/hip circumference ratio, and blood pressures were measured with an automated monitor. Measurements of several lipoproteins and apoproteins were combined into one atherogenic index. RESULTS: The percentage of fat was related to the atherogenic index (p = 0.38; p > 0.01) and insulin level (p = 0.78; p > 0.001). Aerobic capacity was inversely related to the atherogenic index (p = -0.27; p > 0.05) and insulin level (p = 0.72; p > 0.001). The waist/hip ratio was not related to the risk factors, and blood pressures were not related to fatness or aerobic capacity. In multiple regression analyses, only fatness explained significant independent proportions of the variance in the atherogenic index and insulin level. After control for fatness, the black children had higher insulin levels (p > 0.05). CONCLUSION: At early ages (7- to 11-year-old children), fatness was related to risk factors for cardiovascular disease and diabetes. PMID- 7996355 TI - Urinary free cortisol values in children under stress. AB - Children with adrenocortical insufficiency are commonly instructed to increase their baseline glucocorticoid replacement doses by three to five times during periods of stress such as surgery or febrille illness. We conducted this to determine whether these recommendations reflect the actual change in urinary free cortisol (UFC) output during stress. The 24-hour UFC excretion was determined in 78 children who were admitted to a general pediatric department or intensive care unit with temperature > 38.7 degrees C, after major surgery, or during status epilepticus; we reevaluated 43 of the patients 2 weeks after recovery. In addition, the 24-hour UFC levels were determined in 127 healthy children aged 1.8 to 17 years. The UFC level positively correlated with age (r = 0.254; p < 0.001). The amount of UFC per gram of creatinine was inversely correlated with age (r = 0.255; p < 0.001). The amount of UFC per surface area was independent of age. The mean change in the level of UFC per square meter surface area was highest among children who had cardiothoracic surgery and those with multiple trauma. The increase in UFC level during bacterial infection was significantly greater than that during viral infection. The current recommendation to increase the dose to three to five times the baseline glucocorticoid dose during times of stress may underestimate the changes in UFC found in some patients with major surgery, trauma, or certain serious bacterial infections. Production rate studies are needed to prove this point. PMID- 7996356 TI - Familial autoimmune enteropathy with circulating anti-bullous pemphigoid antibodies and chronic autoimmune hepatitis. AB - In a family of four children (two boys and two girls), the two brothers had severe, protracted watery diarrhea beginning at 2 and 3 weeks of life, respectively. Duodenal mucosa in both patients showed total villous atrophy and severe inflammatory infiltration of the entire bowel. The first patient also had lymphoid cell infiltration of the pancreas and died at 6 weeks of age. The second boy is alive at 2 years of age and is immunocompetent, but still receives total parenteral nutrition. Indirect immunofluorescence studies revealed circulating antibodies to enterocytes, smooth muscle, thyroid, and islet cells. Bullous pemphigoid antibodies (230 and 180 kd), specific for hemidesmosomal proteins and usually associated with a subepidermal blistering skin disease, were detected by direct and indirect immunofluorescence studies and by Western immunoblot. A diagnosis of autoimmune hepatitis was made, based on evidence of chronic active hepatitis and circulating anti-smooth muscle antibody. Immunosuppressive treatments induced partial clinical remission of the diarrhea but no resolution of the small bowel injury. At 16 months of age, remission of the diarrhea occurred, but persistent autoimmune hepatitis led us to maintain treatment with prednisone and azathioprine, and later with cyclosporine. In this child, as in other patients with autoimmune disease, the link between autoantibodies and organ damage remains uncertain but immunosuppressive treatment is indicated. PMID- 7996357 TI - Renal function and histopathologic changes in children after liver transplantation. AB - Up to 60% reduction of renal function has been reported after orthotopic liver transplantation (OLT) in patients receiving cyclosporine. We prospectively investigated renal function and histopathology in 16 children on triple immunosuppression therapy during 3 years after OLT. Cyclosporine was administered in 3 doses/day to preschool children. The median age at OLT was 5.4 years. Determinations of chromium 51-labeled ethylenediaminetetraacetic acid, p = aminohippuric acid, lithium, and sodium clearances, measurements of serum and urinary electrolytes, and urinary concentration tests were performed. Renal biopsy specimens were taken 18 and 36 months after transplantation. The mean glomerular filtration rate was 121.5 ml/min per 1.73 m2 before transplantation, 86.3 at discharge, and 119.4 36 months after OLT. Hyperuricemia, hyperkalemia, and reduced urinary concentrating capacity were common. Hyperkalemia occurred in 13% to 19% of the patients, only during the first 6 months. Hyperuricemia and reduced concentrating capacity occurred with incidences of 17% to 44% and 40% to 63%, respectively. Histopathologic changes were mild, and severe nephrotoxic effects of cyclosporine was not seen. However, tubular atrophy, mesangial matrix increase, and mesangial cell proliferation were common. We conclude that triple immunosuppression with cyclosporine administration, in three doses per day, to small children and careful renal follow-up ensure good renal function after OLT. PMID- 7996358 TI - Bone mineral density after renal transplantation in children. AB - Longitudinal bone mineral changes after renal transplantation were studied in 14 children aged 8 +/- 4 years. Combination immunosuppressive therapy was given to all patients (prednisone, azathioprine, cyclosporine). Bone mineral density (BMD) measurements of the first through fourth lumbar vertebrae by dual-energy X-ray absorptiometry were performed within 1 year preceding renal transplantation and 6, 12, and 24 months afterward (M0, M6, M12, and M24, respectively). The results of BMD obtained in grams of hydroxyapatite per square centimeter of spine projected area were subsequently transformed to standard deviation scores for a normal pediatric population. In addition, we used a mathematical spine volume correction to give the results in grams per cubic centimeter. All patients had a well-functioning renal graft at M6, M12, and M24 and a normal serum creatinine level. Significant decreases in BMD, standard deviation score, and spine volume corrected BMD were observed 6 months after renal transplantation (p < 0.05, p < 0.01, and p < 0.01 respectively); the median loss of BMD and spine volume corrected BMD was 9.2% and 15.6% at M6, respectively, and the median serum parathyroid hormone level dropped from 125 to 34 pg/ml. Between M6 and M12, BMD increased significantly up to 95% (median) of pretransplantation values and reached 97.2% (median) at M24. Similar but less marked improvement was observed in spine volume-corrected BMD results, reaching 87.7% and 87.4% at M12 and M24, respectively. A negative correlation was found between the cumulative prednisone dose and BMD in grams per square centimeter at M6 (r2 = 0.603; p = 0.006), M12 (r2 = 0.532; p = 0.015), and M24 (r2 = 0.40; p = 0.014). There was no correlation between cumulative prednisone dose and spine volume-corrected BMD or standard deviation score. Mean 6-month cyclosporine levels did not correlate with any measure of BMD. We conclude that after renal transplantation children have a significant decrease of BMD during the first 6 months after the operation, despite normal graft function and growth improvement. PMID- 7996359 TI - A multiinstitutional survey of the Wiskott-Aldrich syndrome. AB - The Wiskott-Aldrich syndrome is an X-linked primary immunodeficiency originally characterized by the clinical triad of thrombocytopenia, eczema, and immunodeficiency. We collected clinical and laboratory information on 154 unselected patients with Wiskott-Aldrich syndrome to define better the clinical expression of this disorder. The classic triad of thrombocytopenia with small platelets, recurrent otitis media, and eczema was seen in only 27% of the study population; 5% of the study population had only infectious manifestations, and 20% of the study group had only hematologic manifestations before diagnosis. The results of immunologic evaluations varied from one patient to another and the course of the disorder varied tremendously, even within a single kindred. We conclude that many patients with Wiskott-Aldrich syndrome have an atypical presentation and that a panel of diagnostic tests is often required to establish the diagnosis. Two high-risk subgroups were identified in the study population: patients with platelet counts < 10 x 10(9)/L (< 10,000/mm3) at the time of diagnosis were at high risk of bleeding, and patients with autoimmune disorders were at increased risk of having a malignancy. PMID- 7996360 TI - Partial albinism with immunodeficiency (Griscelli syndrome). AB - Partial albinism with immunodeficiency is a rare and fatal immunologic disorder characterized by pigmentary dilution and variable cellular immunodeficiency. To define the phenotype, therapy, and outcome, we retrospectively analyzed seven consecutive patients. Primary abnormalities included a silvery-grayish sheen to the hair, large pigment agglomerations in hair shafts, and an abundance of mature melanosomes in melanocytes, with reduced pigmentation of adjacent keratinocytes. Clinical onset occurred between the ages of 4 months and 4 years and was characterized by accelerated phases (lymphohistiocytic infiltration of multiple organs, including the brain and the meninges), triggered by viral and bacterial infections. Characteristic laboratory features included pancytopenia, hypofibrinogenemia, hypertriglyceridemia, and hypoproteinemia. Consistent immunologic abnormalities were characterized by absent delayed-type cutaneous hypersensitivity and impaired natural killer cell function. Some patients had secondary hypogammaglobulinemia, impaired major histocompatibility complex mediated cytotoxic effects, a decreased capacity of lymphocytes to trigger a mixed lymphocyte reaction, or various functional granulocytic abnormalities. The disease seems to be invariably lethal without bone marrow transplantation; the mean age at the time of death was 5 years. Bone marrow transplantation has been performed in three cases; two patients died in the immediate posttransplantation period of infectious complications, but one patient is cured after a follow-up of 5 years. We conclude that partial albinism with immunodeficiency (Griscelli syndrome) can be differentiated from Chediak-Higashi syndrome by pathognomonic histologic features. One of the underlying immunologic defects may be a defective function of natural killer cells, predisposing the patient to virus-associated hemophagocytic syndrome or accelerated phases. The prognosis is very poor unless early bone marrow transplantation is carried out. PMID- 7996361 TI - Bone marrow transplantation for autosomal recessive osteopetrosis. A report from the Working Party on Inborn Errors of the European Bone Marrow Transplantation Group. AB - The outcomes of 69 patients who received allogeneic bone marrow grafts for autosomal recessive osteopetrosis in the period between 1976 and 1994 were analyzed retrospectively. Four patients received bone marrow transplants (BMT) without prior myeloablative conditioning; transient osteoclast function was demonstrated in one of them. Sixty-five patients received myeloablative pretreatment. Recipients of a genotypically human leukocyte antigen (HLA) identical BMT had an actuarial probability for 5-year survival, with osteoclast function, of 79%; recipients of a phenotypically HLA-identical bone marrow graft from a related or unrelated donor, or one HLA-mismatched graft from a related donor, had an actuarial probability for 5-year survival, with osteoclast function, of 38%; patients who received a graft from an HLA-haplotype mismatched related donor had a probability for 5-year survival of only 13%. The main problems in haplotype-nonidentical BMT were graft failure and BMT-related complications such as sepsis, bleeding, and interstitial pneumonia. Osteoclast function developed in all patients with full engraftment. Recovery of osteoclast function was associated with severe hypercalcemia in 24% of the patients with engraftment, especially those older than 2 years of age. At the time of BMT, severe visual impairment was present in 35% of the patients; of the 15 patients who had visual impairment at the time that a successful BMT was performed, two had improvement after BMT (13%). Within the total group, one patient had neurodegeneration. Engraftment of healthy donor cells had no influence on the progression of that abnormality and BMT thus had no beneficial effect on this phenotype of osteopetrosis. In general, however, early BMT remains the only curative treatment for autosomal recessive osteopetrosis. PMID- 7996362 TI - Clinical outcome of long-term management of patients with vitamin B12 unresponsive methylmalonic acidemia. AB - We performed a retrospective study of all patients with methylmalonic acidemia diagnosed during the past 20 years. Only those patients who were nonresponsive to vitamin B12 in vivo and in vitro were included. The final study group consisted of 26 patients, of whom 16 had a neonatal (early) onset; in 10 patients the diagnosis was made after 2 months to 2.2 years (late onset). Of the early-onset patients, 14 (87%) died, with a mean survival time of 1.5 years (range, 10 days to 2.5 years), whereas four of the late-onset patients (40%) died (range, 1.2 to 15 years). At present, eight patients are alive; their mean age is 4.6 years (range, 1 to 10 years). In the early 1970s, treatment was based on the principles of treating patients with phenylketonuria: restricting natural protein intake and supplementing essential amino acids, vitamins, and trace elements. After about 1980, nasogastric tube feeding became a mainstay of the therapy, natural protein restriction became stricter, and the use of essential amino acid mixtures diminished. Carnitine was added to the therapy and, in later years, metronidazole. Since these changes were implemented, the number of episodes of metabolic decompensation and hospitalizations has decreased. Mean survival time of the patients, in particular those with early onset, has only slightly improved, partly because of psychosocial problems in many of these families. Almost all the patients, especially those with early onset, had some degree of neurologic impairment and mental retardation, and many patients were at less than 2 SD for weight or height or both. In contrast, the neurologic and mental status of the late-onset patients was frequently normal, and their weight and height were more often within normal limits. Our results show that the treatment of methylmalonic acidemia still poses considerable problems; despite intense medical efforts and familial stress, the prognosis for the early-onset patients is disappointing. The patients with late-onset disease, however, appear to have a fairly good prognosis with the present therapeutic approach. Liver transplantation or possibly genetic therapy might improve our results in the future. PMID- 7996364 TI - Acquired von Willebrand disease in twins with autoimmune hypothyroidism: response to desmopressin and L-thyroxine therapy. AB - Because of menorrhagia, a 13-year-old girl was found to have type I von Willebrand disease and then chronic autoimmune thyroiditis with hypothyroidism. All clinical and laboratory evidence of von Willebrand disease resolved transiently after infusion of desmopressin, and permanently with L-thyroxine therapy. We recommend investigation for hypothyroidism in patients with newly diagnosed acquired von Willebrand disease. PMID- 7996363 TI - Effects of a long-term transfusion regimen on sickle cell-related illnesses. AB - The efficacy of a long-term transfusion regimen in preventing sickle cell disease complications is unknown. We examined 17 patients before, during, and after transfusion for cerebral vascular accident and vaso-occlusive crisis. Total hospitalization rate, as well as admissions for vaso-occlusive crisis, cases of acute chest syndrome, and bacterial infections decreased while patients were on a transfusion regimen. PMID- 7996365 TI - Perianal pseudoverrucous papules and nodules after surgery for Hirschsprung disease. AB - We report two patients with Hirschsprung disease in whom severe diarrhea and a distinctive diaper dermatitis developed after delayed ileoanal anastomosis. The perianal papulonodular lesions cleared in months or years without specific treatment after resolution of the diarrhea. These perianal pseudoverrucous papules and nodules represent a peculiar form of primary irritant diaper dermatitis, distinct from Jacquet erosive diaper dermatitis and granuloma gluteale infantum. PMID- 7996366 TI - Adult and infantile Gaucher disease in one family: mutational studies and clinical update. AB - Molecular analysis and clinical updates are provided on a previously reported mother and adult son with Gaucher disease; two other children died with acute neuronopathic (type 2) Gaucher disease. The mother and son have the identical genotype (370/444) but very different clinical manifestations. These findings illustrate the need for additional studies before families with newly diagnosed Gaucher disease undergo counseling. PMID- 7996368 TI - Recurrent group B streptococcal infections in infants: clinical and microbiologic aspects. AB - OBJECTIVE: To describe the potential for recurrence of group B streptococcal (GBS) infection in infants, using pulsed-field gel electrophoresis as an epidemiologic tool. DESIGN: Retrospective review of cases identified by laboratory records and review of the literature. SETTING: Neonatal nurseries of a county hospital system. METHODS: Retrospective review of infants with second episodes of GBS bacteremia or meningitis. Digestion of chromosomal DNA with the restriction enzyme Sma I and separation of fragments by use of contour-clamped homogeneous electric field. RESULTS: Nine cases of recurrent GBS infection were identified during a 14-year period. Eight of the nine infants were born at 25 to 36 weeks of gestation, and one was born at term. The first episode of invasive GBS infection occurred at a mean age of 10.4 days (median, 3 days; range, 1 to 27 days). Parenteral antibiotic therapy was administered for a mean of 13.9 days (median, 14 days; range, 10 to 21 days). Recurrence occurred at a mean age of 42.3 days (median, 48 days; range, 23 to 68 days). One patient died during the second episode; eight infants survived to discharge home. Of seven sets of isolates analyzed from first and second GBS episodes, five were confirmed to be the same genotypically. CONCLUSION: Recurrence of GBS disease in infants may be associated with the original infecting strain or a second acquired strain. PMID- 7996367 TI - Intravenous immune globulin prophylaxis of late-onset sepsis in premature neonates. AB - To determine whether a single dose of intravenously administered immune globulin (IVIG) decreases late-onset sepsis in premature infants, we prospectively entered 753 neonates with birth weight 500 to 2000 gm, gestation < or = 34 weeks, and age < or = 12 hours into a multicenter, double-blind, controlled trial. Infants were randomly selected to receive a single intravenous infusion, 10 ml/kg, of either IVIG (500 mg/kg) or albumin (5 mg/kg) and were observed for 8 weeks for infection. Maternal and neonatal risk factors for infection did not differ between groups. Although serum IgG values before infusion were related to gestation (R = 0.62), the change in serum IgG or half-life of IgG after IVIG infusion was not (R < or = 0.09). The serum IgG concentration was increased (p < 0.05) in IVIG-treated patients for 8 weeks. There were 88 episodes of late-onset sepsis in 79 neonates (10.5%). Causative organisms included the following: Staphylococcus epidermidis (37 episodes), Enterococcus (9), Staphylococcus aureus (7), Candida (6), Escherichia coli (6), and multiple organisms (11). Sepsis, death, and death as a result of infection were unaffected by treatment. We conclude that a single infusion of IVIG, 500 mg/kg, shortly after birth was not effective prophylaxis for late-onset infection in premature neonates. Future studies of late-onset sepsis prophylaxis should consider IVIG with known pathogen specific antibody concentrations against organisms causing these infections, in particular S. epidermidis. PMID- 7996369 TI - Effect of different surfactants on pulmonary group B streptococcal infection in premature rabbits. AB - OBJECTIVES: To evaluate the effects of different surfactants on pulmonary infection with group B streptococci in premature rabbits and to examine the effects of different surfactants on pulmonary alveolar macrophage function of newborn rabbits. MODEL: Preterm and term rabbit pups. METHODS: Rabbit pups were infected with GBS aerosols followed by intratracheal administration of either calf lung surfactant extract, minced porcine lung surfactant (Curosurf), synthetic surfactant (Exosurf Neonatal), minced bovine lung surfactant (Survanta), human amniotic fluid-derived surfactant, rabbit surfactant, saline vehicle, or no treatment. Intrapulmonary clearance of GBS was determined by comparing bacterial counts in left lungs cultured immediately after aerosol infection with similarly infected lungs analyzed 4 hours after surfactant therapy. Phagocytosis of streptococci was ascertained by microscopic examination of the right lungs fixed in situ at 4 hours. For comparison, an in vitro method was used to measure growth of GBS in the different surfactants. RESULTS: Preterm animals had a sixfold increase in pulmonary bacterial growth compared with a slight decrease in intrapulmonary GBS in term animals when all were delivered by cesarean section (p < 0.05). In premature rabbits, GBS proliferation was lowest in animals treated with Exosurf Neonatal and highest in animals receiving Curosurf and human amniotic fluid-derived surfactant (p < 0.05). None of the surfactants promoted accelerated growth of GBS in comparison with control animals. Similar growth of GBS was seen in in vitro cultures. Intrapulmonary phagocytosis of GBS in premature pups was not altered by any of the surfactants. In term rabbit pups, the following measures of macrophage population kinetics remained normal at 1 and 24 hours after surfactant administration: viability, cell numbers based on lung lavage, and in vivo incorporation of thymidine. CONCLUSIONS: Surfactants used in clinical practice do not accelerate the in vivo growth of group B streptococci in the lungs of preterm rabbits. Some surfactants inhibit streptococcal proliferation. The effects of different surfactants are not explained by changes in macrophage function. PMID- 7996370 TI - Perinatal outcomes of a large cohort of extremely low gestational age infants (twenty-three to twenty-eight completed weeks of gestation). AB - OBJECTIVES: To determine gestational age (GA)-specific mortality rates; the effects of GA, birth weight, sex, and multiple gestation on mortality rates; short-term morbidity for infants born at 23 to 28 weeks GA; and impairment rates at a corrected chronologic age of 18 months for those born at 23 to 25 weeks GA. METHODS: A data base analysis was performed with a linked obstetric and a neonatal database. GA was determined by obstetric data and confirmed by early ultrasonography (available in 88%) on all births < 30 weeks GA at British Columbia's tertiary perinatal center from 1983 to 1989. RESULTS: Of 1024 births occurring between 23 and 28 weeks GA, 911 were live born. The mortality rate decreased with increasing GA: 84% at 23 weeks; 57% at 24 weeks; 45% at 25 weeks; 37% at 26 weeks; 23% at 27 weeks; and 13% at 28 weeks GA. For each GA, mortality rate versus birth weight plots showed a decreasing mortality rate with increasing birth weight, except for infants who were large for GA. Male infants had a higher mortality rate than female infants (odds ratio, 1.8; confidence interval, 1.4 to 2.5). Twins fared worse than singletons with a decreasing effect from 24 weeks GA (odds ratio, 10.3) to no effect at 28 weeks GA. The median number of days supported by mechanical ventilation and the length of stay in the neonatal intensive care unit decreased markedly with increasing GA. Eighteen-month outcome of survivors between 23 and 25 weeks GA with 93% follow-up rate revealed an overall impairment rate of 36%, but 6 of the 9 surviving 23-week infants had major impairments. CONCLUSIONS: The GA-specific perinatal outcome results of this large cohort provide information to assist in perinatal management decision making and for counseling parents prenatally. PMID- 7996371 TI - Parenteral nutrient needs of very low birth weight infants. AB - OBJECTIVE: To determine nitrogen and mineral needs in parenterally nourished very low birth weight infants. DESIGN: Prospective observational study. SETTING: Neonatal intensive care unit. PATIENTS: Twenty-four very low birth weight infants (< 1.2 kg) expected to receive parenteral nutrition (PN) exclusively for 3 weeks beginning 3 days after birth. INTERVENTIONS: Infants received PN solutions according to nursery protocol. Serial 24-hour balance studies were conducted twice weekly. Clinical therapies were tabulated. MAIN OUTCOME MEASURES: Intake, urinary excretion, and apparent retention of nitrogen, sodium, potassium, zinc, copper, calcium, phosphorus, and magnesium after initiation of PN. RESULTS: Although urinary K, Zn, Ca, P, and Mg excretion (but not N, Na, and Cu excretion) increased after PN therapy was begun, net nutrient retention increased significantly above baseline for all nutrients. Average weekly nutrient retention was significantly below intrauterine estimates of nutrient accretion for N, Na, Ca, P, and Cu; closely approximated estimates for Zn; and significantly exceeded those for K and Mg. Regression analysis was used to predict parenteral nutrient intakes that would support postnatal nutrient retentions equivalent to the intrauterine estimates. Postnatal therapy with dexamethasone affected N, P, and K excretion and retention. CONCLUSIONS: Soon after PN administration is begun, positive nutrient balance may be achieved early in the neonatal period. The magnitude of this effect remains uniform during PN administration. Adjustments in parenteral nutrient intake are needed to provide nutrient intakes sufficient to support postnatal retention at rates similar to those of intrauterine accretion. These data should be considered in the design of future studies to determine optimal PN needs of very low birth weight infants. PMID- 7996373 TI - Nebulized furosemide in infants with bronchopulmonary dysplasia. AB - The effects of 0.1 mg, 0.25 mg, 0.50 mg, and 1.0 mg of nebulized furosemide per kilogram of body weight on pulmonary functions were studied in eight preterm infants with bronchopulmonary dysplasia who were supported by mechanical ventilation. Doses of 1 mg/kg significantly improved lung compliance (51% at 2 hours after nebulization), pulmonary resistance (28% at 1 hour), and tidal volume (43% at 1 hour), starting as early as 30 minutes after the dose; the effect lasted for at least 4 hours in many of the infants and was not associated with diuresis or renal side effects. PMID- 7996372 TI - Predictive value of neonatal electroencephalograms before and during extracorporeal membrane oxygenation. AB - We studied the prognostic significance of electroencephalograms recorded serially at 2- to 4-day intervals during the acute neonatal course of 119 near-term infants with severe respiratory failure treated by venoarterial extracorporeal membrane oxygenation (ECMO). A poor prognosis was defined as early death (n = 27), an abnormally low developmental assessment score (n = 14), or cerebral palsy (n = 14) at 12 to 45 months of age. The only electroencephalographic abnormalities that were significantly related to a poor prognosis were burst suppression (B-S) and electrographic seizure (ES). The 30 infants with two or more recordings of B-S or ES, when compared with the 58 neonates without such electroencephalographic abnormalities, had an odds ratio for a poor prognosis of 6.6 (95% confidence limits, 2.2 to 20.2). The 31 infants with a single ES or B-S recording did not have a significantly increased risk for a poor prognosis. Cardiopulmonary resuscitation immediately before ECMO (n = 8) and the lowest systolic blood pressure before or during ECMO were significantly related to the occurrence of ES or B-S recordings. There was no significant predilection of ES for either cerebral hemisphere. We conclude that in near-term neonates with respiratory failure, serial electroencephalographic recordings are of predictive value, and may facilitate clinical care including the decision to initiate or to continue ECMO. PMID- 7996374 TI - Treatment of childhood steroid-resistant idiopathic nephrosis with a combination of cyclosporine and prednisone. French Society of Pediatric Nephrology. AB - Sixty-five children with steroid-resistant idiopathic nephrosis were treated with cyclosporine, 150 to 200 mg/m2, in combination with prednisone, 30 mg/m2, daily for 1 month and on alternate days for 5 months. Renal biopsy had shown minimal change disease in 45 children and focal segmental glomerular sclerosis in 20. Twenty-seven patients achieved complete remission. At latest examination, 14 to 60 months after initiation of the treatment (mean, 38 months), 17 patients were in complete remission, 8 had had a relapse but had become steroid sensitive, and 2 had a nephrotic syndrome. Four children responded partially to the treatment. At latest examination, 28 to 58 months after initiation of the treatment, 1 was in complete remission, 1 was in partial remission, 1 had a nephrotic syndrome, and 1 had end-stage renal failure. Thirty-four children did not respond to the combined treatment. At latest examination, 12 to 63 months after initiation of the treatment (mean, 38 months), 5 of these patients were in complete remission, 2 were in partial remission, 15 had a persistent nephrotic syndrome (with moderate renal failure in 5), and 12 children had end-stage renal failure. Forty eight percent of the patients with minimal change disease and 30% of those with focal segmental glomerular sclerosis achieved complete remission (p = 0.27). We conclude that cyclosporine in combination with prednisone can induce a complete remission in some children with steroid-resistant idiopathic nephrosis. PMID- 7996376 TI - Effects of pentoxifylline on sputum neutrophil elastase and pulmonary function in patients with cystic fibrosis: preliminary observations. AB - High concentrations of free human neutrophil elastase in bronchial epithelial fluid are believed to be a major factor in the evolution of pulmonary injury in cystic fibrosis (CF). To test this hypothesis, we studied pentoxifylline, a compound that inhibits tumor necrosis factor alpha transcription and its stimulatory effect on polymorphonuclear neutrophils, in patients with CF who had chronic Pseudomonas bronchitis. Subjects older than 11 years of age randomly received placebo or pentoxifylline (1600 mg/day) orally, in a double-blind fashion, for 6 months. Pulmonary function and sputum elastase concentrations were determined before therapy and bimonthly during therapy; compliance was determined by measuring serum drug concentrations. Of the 16 patients who completed the study, 9 received pentoxifylline. The sputum elastase concentrations among placebo recipients were significantly increased from baseline at 4 and 6 months (F = 3.44; p < 0.05); the values remained unchanged in the treatment group. The mean forced vital capacity for the placebo group decreased from 59.2% +/- 15.4% predicted at baseline to 52.0% +/- 12.9% predicted at 6 months; the values in the treatment group remained largely unchanged. The forced vital capacity improved between baseline and 6 months for four of nine pentoxifylline recipients and none of the seven control patients (p = 0.09). During the study, four of seven placebo recipients experienced a significant pulmonary exacerbation compared with one of nine treated patients (p = 0.077). These findings support the hypothesis that polymorphonuclear neutrophil elastase is a factor in the evolution of CF lung disease; further studies are needed to define the role of pentoxifylline in the treatment of CF. PMID- 7996375 TI - Bioequivalence of a generic slow-release theophylline tablet in children. AB - OBJECTIVE: To determine whether a generic slow-release theophylline tablet (manufactured by Sidmak Laboratories, Inc.) is therapeutically equivalent to a proprietary theophylline tablet, Theo-Dur, in children. DESIGN: Prospective, randomized, double-blind, crossover trial. SETTING: Multicenter clinics. PATIENTS: 38 children, 6 to 16 years of age, with asthma. INTERVENTIONS: Individualized doses of Theo-Dur or generic tablet every 12 hours for 5 days. MEASUREMENTS AND MAIN RESULTS: During the last 24 hours of each regimen, theophylline serum concentrations were measured serially and a standardized exercise stress test was performed at 24 hours (trough serum concentration). Neither formulation effectively blocked the response to exercise; the maximum decrease in forced expiratory volume in the first second was 26.1% +/- 18.9% with Theo-Dur and 24.8% +/- 19.7% with the generic product (p = 0.68; beta = 0.08). The mean +/- SD peak serum concentrations were 18.0 +/- 3.0 micrograms/ml with Theo-Dur and 18.7 +/- 3.7 micrograms/ml with the generic tablet; the trough serum concentration was < 10 micrograms/ml in 15 subjects after administration of Theo Dur and in 20 subjects after administration of the generic product. There were no significant differences in relative extent of absorption or the time to reach peak serum concentration. CONCLUSIONS: This generic formulation and Theo-Dur are bioequivalent in children. However, these results cannot be extrapolated to slow release theophylline formulations that have not been approved by the U.S. Food and Drug Administration as equivalent to Theo-Dur. PMID- 7996377 TI - Long-term itraconazole prophylaxis against Aspergillus infections in thirty-two patients with chronic granulomatous disease. AB - We conducted a prospective, open study of oral itraconazole therapy (5 and then 10 mg/kg per day) to assess tolerance and potential efficacy in preventing fungal infections in patients with chronic granulomatous disease. Thirty-two patients were enrolled in one center between 1985 and 1991. Tolerance was excellent in all cases. Poor compliance was suspected in three cases. Two patients were excluded from efficacy analysis because itraconazole was used as part of therapy for pulmonary aspergillosis. Of 30 patients, 3 developed a fungal (Aspergillus) lung infection, an incidence 3.4/100 patient-years versus 11.5 in a historical control group that did not receive any prophylaxis (p = 0.13) and 9.55 in a historical group of patients who received daily ketoconazole prophylaxis (p = 0.19). The percentage of patients infected with Aspergillus was significantly different: 10% in the itraconazole group versus 34.4% in the untreated group (p = 0.013). These results require further evaluation through a comparative randomized trial to assess the possible benefit of itraconazole prophylaxis in patients with chronic granulomatous disease. PMID- 7996378 TI - Rheological behaviour of saturated polyglycolysed glycerides. AB - Seven saturated polyglycolysed glycerides (Gelucires) of melting points varying from 42 to 53 degrees C and hydrophilic-lipophilic balance values from 2 to 14 were selected. Their rheological behaviour was determined by adjustment of the flow curves to the Ostwald power-law and by statistical assessment of the flow index. The flow of Gelucires was slightly shear thickening. This shear thickening rose when the temperature and the lipophilic specificity of the Gelucire increased. This behaviour accounted for a reorganization of the particles under the shear which became easier when the temperature increased and when the degree of condensation of the polyethylene glycol chains decreased with lipophilicity of the Gelucires. PMID- 7996379 TI - The power-consumption-controlled extruder: a tool for pellet production. AB - Based on the assumption that there is a link between power consumption of an extruder and pellet properties, a control circuit for power consumption was developed. Powder and granulation liquid are fed separately into a twin-screw extruder. The power consumption is controlled by varying the pump rate at a given powder-feed rate; consequently each level of power consumption results in a specific water content of the extrudate for a particular formulation. The shape of pellets depends almost entirely on the level of power consumption irrespective of formulation. The size of dry pellets is additionally affected by a shrinking factor which depends on the water content. The power-consumption-controlled extruder is an appropriate tool for the production of pellets. The system is able to adapt the water content for a formulation automatically. PMID- 7996380 TI - Calcitonin and insulin in isobutylcyanoacrylate nanocapsules: protection against proteases and effect on intestinal absorption in rats. AB - One of the major limiting steps for the absorption of peptide drugs from the intestine is proteolytic degradation. To slow this degradation, human calcitonin was trapped in polyacrylamide nanoparticles, and human calcitonin and insulin were encapsulated with polyisobutylcyanoacrylate. Human calcitonin trapped in polyacrylamide nanoparticles showed no delayed release characteristics and thus would not provide protection from proteases. Proteolytic degradation of human calcitonin and insulin in polyisobutylcyanoacrylate nanocapsules was slower than the free peptides in solution. The plasma pharmacokinetic profiles were consistent with increased survival time of the peptides in the intestine, with higher plasma concentrations of the peptides in the later time samples compared with the controls. However, the nanocapsules gave no significant overall enhancement of peptide absorption. This led to the conclusion that the nanocapsules released the peptides into the intestinal lumen, with small amounts then being absorbed but the rest largely degraded. PMID- 7996381 TI - Plasma levels of peptide YY correlate with cisplatin-induced emesis in dogs. AB - The effect of cisplatin on plasma peptide YY (PYY) and 5-hydroxytryptamine (5-HT) concentrations was determined in conscious dogs (n = 6 per group) pretreated with either saline, or the 5-HT3-receptor antagonists ondansetron or granisetron. Cisplatin (3.0 mg kg-1, i.v.) caused emesis (18.8 +/- 2.9 episodes; 75-284 min) and significantly increased the mean area under the curve (AUC) over a 6-h period of plasma PYY concentrations (7.4 +/- 1.8 to 11.5 +/- 3.7 ng) in all saline pretreated dogs, whereas the mean AUC of plasma 5-HT concentrations did not significantly increase (34.7 +/- 7.4 vs 35.6 +/- 12.3 pM h). The concentrations of PYY correlated closely with the incidence of emesis (r = 0.99). In animals pretreated (36 min) with ondansetron (0.316 mg kg-1, i.v.) or granisetron (0.316 mg kg-1, i.v.), the number of cisplatin-induced emetic episodes was significantly (P < 0.005) decreased compared with control. In animals receiving cisplatin and pretreated with ondansetron, PYY concentrations were not significantly altered, whereas the mean AUC of plasma concentrations of 5-HT over 6 h increased (35.6 +/ 12.3 to 82.3 +/- 34.6 pM h; P < 0.05). In animals receiving cisplatin and pretreated with granisetron, plasma concentrations of 5-HT were not significantly altered, whereas the mean AUC of plasma PYY concentrations were significantly reduced compared with control (6.2 +/- 1.7 vs 11.5 +/- 3.7 ng h).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7996383 TI - Investigation of synergism with combinations of dibromopropamidine isethionate or propamidine isethionate and polymyxin B. AB - Combinations of polymyxin B and dibromopropamidine isethionate exhibited synergistic inhibitory and bactericidal activity against Pseudomonas aeruginosa, Enterobacter cloacae, Proteus mirabilis, Escherichia coli and Staphylococcus aureus. Similar results were obtained with polymyxin B plus propamidine combinations except that propamidine was not as active as dibromopropamidine and the combination of polymyxin B plus propamidine against S. aureus only had additive activity. The antibacterial agents were tested in solutions and in a cream formulation. The findings indicate a potential for the use of selected combinations of these antibacterial agents in the treatment of wound and superficial eye infections. PMID- 7996382 TI - U-46619-induced ischaemic electrocardiographic changes in rats: preventive effects of prostacyclin and nitroglycerin. AB - The anti-anginal effect of nitroglycerin and prostacyclin was examined using, as an index, the ischaemic electrocardiogram (ECG) change (ST elevation) induced by intracoronary arterial injection of 9,11-dideoxy-11 alpha,9 alpha-epoxymethano PGF2 alpha (U-46619), a stable thromboxane A2 agonist, in anaesthetized rats. The ST elevation induced by U-46619 (5-20 micrograms kg-1, i.c.a.) was dose-dependent and reproducible. U-46619-induced ST elevation was markedly prevented by the pretreatment of intravenous administration of prostacyclin (0.01 micrograms kg 1), and to a lesser extent by nitroglycerin (0.3 mg kg-1). Simultaneously, platelet count decreased significantly in the coronary arterial blood which indicated that platelet aggregation was enhanced by U-46619. The decrease of platelet count in coronary arterial blood at the time of ST elevation was significantly suppressed by prostacyclin (0.1 microgram kg-1, i.v.), but not by nitroglycerin (0.3 mg kg-1, i.v.). These results suggest that the ST elevation induced by intracoronary arterial injection of U-46619 may be derived from spasm of coronary artery and platelet aggregation in the intracoronary artery in rats. PMID- 7996384 TI - pH-dependent and carrier-mediated transport of salicylic acid across Caco-2 cells. AB - The transport of monocarboxylic acid drugs such as salicylic acid was examined in the human colon adenocarcinoma cell line, Caco-2 cells that possess intestinal epithelia-like properties. [14C]Salicylic acid transport was pH-dependent and appeared to follow the pH-partition hypothesis. However, 10 mM unlabelled salicylic acid significantly reduced the permeability coefficient of [14C]salicylic acid. Kinetic analysis of the concentration dependence of the permeation rate of salicylic acid across Caco-2 cells showed both saturable (Kt = 5.28 +/- 0.72 mM Jmax = 36.6 +/- 3.54 nmol min-1 (mg protein)-1) and nonsaturable (kd = 0.37 +/- 0.08 microL min-1 (mg protein)-1) processes. The permeation rate of [14C]salicylic acid was competitively inhibited by both acetic acid and benzoic acid, which were demonstrated in our previous studies to be transported in the carrier-mediated-transport mechanism which is responsible for monocarboxylic acids. Furthermore, certain monocarboxylic acids significantly inhibited [14C]salicylic acid transport, whereas salicylamide and dicarboxylic acids such as succinic acid did not. From these results, it was concluded that the transcellular transport of [14C]salicylic acid across Caco-2 cells is by the pH-dependent and carrier-mediated transport mechanism specific for monocarboxylic acids. PMID- 7996385 TI - The disposition of the tolcapone 3-O-methylated metabolite is affected by the route of administration in rats. AB - Catechol-O-methyltransferase (COMT) catalyses the transfer of the methyl group from S-adenyl-L-methionine (SAM) to one of the hydroxy groups of a catechol, usually the hydroxy group in position 3. COMT is present mainly in a soluble form (S-COMT) in the cytosol, but a small fraction is bound to cell membranes (MB COMT). MB-COMT has higher affinity for the catechol substrate than does S-COMT by a factor of > 10, and high MB-COMT activity is observed in the intestinal muscle layer. The present study investigates the effect of the administration route on the disposition of the tolcapone 3-O-methylated metabolite following intravenous and oral tolcapone administration in rats. Tolcapone is a substrate for COMT although the 3-O-methylated metabolite produced has no pharmacological actions. The 3-O-methylated metabolite was eliminated very slowly following oral administration of tolcapone, and its concentration approached a plateau level, which was in contrast to the situation following intravenous administration of tolcapone. It is thought that the oral dose of tolcapone receives a high exposure to MB-COMT in the intestinal muscle layer during its absorption, and tolcapone seems to form a complex with MB-COMT having a high affinity constant (i.e. a very low Ki). The fraction of the intravenous dose of tolcapone metabolized to the 3-O methylated metabolite at 10 mg kg-1 was 2.6%, whereas those of the oral doses, which were corrected by the bioavailability, were 5.4% for 20 mg kg-1 and 2.7% for 40 mg kg-1. PMID- 7996386 TI - Hepatobiliary disposition of 3'-azido-3'-deoxythymidine (AZT) in the rat: effect of phenobarbitone induction. AB - Isolated liver with a recirculating perfusate was used to study 3'-azido-3' deoxythymidine (AZT) disposition in phenobarbitone-pretreated rats at 68 microM AZT concentration in the reservoir. Clearance of AZT in the livers obtained from control animals was 0.42 +/- 0.01 (mean +/- s.d.) mL min-1/10 g liver. Over the study period of 105 min, 12.7 +/- 2.6% of the dose was excreted in bile and of this 95% was recovered as 3'-azido-3'-deoxy-5'-O-beta-D glucopyranuronosylthymidine (GAZT). The amount of GAZT found in the perfusate after 105 min of liver perfusion was < 1% of the AZT dose introduced into the reservoir. Phenobarbitone pretreatment of rats resulted in a 5.5-fold increase of AZT clearance. In addition, the area under the perfusate concentration-time curve (AUC0-105 min) for 3'-amino-3'-deoxythymidine (AMT) and for a catabolite of unknown structure was increased 3- and 10-fold, respectively, and the amount of AZT dose excreted in the bile was nearly doubled. Thus phenobarbitone was capable of stimulating both detoxification of AZT to GAZT and bioactivation of AZT to AMT, a catabolite known to be highly toxic to human bone marrow cells. This induction was the result of enhancement of AZT catabolism rather than its transport into the cells, since on incubation of AZT (0-250 microM) with rat isolated hepatocytes, a linear relationship between concentration and amount taken up by the cells was shown. In addition, the rate of AZT uptake was not influenced by KCN, dinitrophenol, or temperature, which is consistent with a simple diffusion of AZT through the hepatocellular membrane.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7996387 TI - Metabolic cage isolation reduces antipyrine clearance in rats. AB - Rats are commonly isolated individually in cages during pharmacokinetic studies. However, isolation-induced changes in drug disposition are not commonly examined. Antipyrine is a marker of hepatic oxidative function and total body water. The purpose of the study was to investigate the effect of individual housing on antipyrine pharmacokinetics. Rats were individually housed in either standard polycarbonate boxes (n = 8) or metabolic cages (n = 10). On day 1 and day 9 rats were administered a single intravenous bolus injection of antipyrine 20 mg kg-1. Blood samples (100 microL) were obtained before and at 20, 40, 60, 90, 120, 180, 240, 300 and 360 min following the administration of the dose. Rats remained in their respective cages between evaluations. Serum antipyrine concentrations were determined by capillary electrophoresis. Pharmacokinetic parameters were estimated by model-independent methods. Antipyrine clearance was reduced by 38.4% in rats isolated in metabolic cages for eight days (P = 0.013) while the volume of distribution remained unchanged in both rat groups. These data suggest that the isolation of rats in metabolic cage systems may markedly alter the pharmacokinetics of xenobiotics, thus possibly masking experimental outcome. PMID- 7996388 TI - The recognition of a diarylimine as a metabonate produced during incubation of N benzyl-4-chloroaniline with hepatic microsomal preparations. AB - Evidence is presented for the formation of N-benzylidene-4-chloroaniline as a metabonate during the metabolism of N-benzyl-4-chloroaniline. Control studies suggest that the diarylimine is formed as a chemical artifact from the debenzylation products (benzaldehyde and 4-chloroaniline). This novel observation indicates a possible pathway to amide formation from N-benzylanilines via diarylimines as intermediates. PMID- 7996389 TI - Enantioselective pharmacokinetics of homochlorcyclizine: disposition of (+)- and (-)-homochlorcyclizine after intravenous and oral administration of racemic homochlorcyclizine to rats. AB - Concentrations of homochlorcyclizine enantiomers in blood, urine, and tissues of the liver, lung, kidney, brain, heart, spleen, intestine and stomach of rats after drug administration were determined by high-performance liquid chromatography on a chiral stationary phase. After intravenous administration (10 mg kg-1), homochlorcyclizine was rapidly distributed in many tissues, with the highest concentration in lung. No differences were found between enantiomers in blood concentrations. After oral administration (50 mg kg-1), the concentrations of the (+)-isomer in nearly all tissues were higher than those of the (-)-isomer. The AUC0-infinity values of the (+)- and (-)-isomers differed significantly. The absorption of racemic homochlorcyclizine from rat small intestine was not enantioselective. These results suggested that the different concentrations between enantiomers after oral administration were not caused by enantioselective absorption or distribution but rather by preferential first-pass metabolism of the (-)-isomer in the liver. The enantioselectivity of metabolism was also demonstrated by in-vitro experiments. PMID- 7996391 TI - Comparative pharmacokinetic and pharmacodynamic properties of oral and intravenous (+)-sotalol in healthy volunteers. AB - The pharmacokinetic and pharmacodynamic properties of (+)-sotalol (BMY-5763) were studied to analyse the relationship between plasma concentration and QTc prolongation in healthy male volunteers given single oral doses of 50, 100, 200 and 300 mg, repeated oral doses of 200 mg twice daily for 6.5 days, and single intravenous doses of 1.0 and 1.5 mg kg-1. The plasma concentration of (+)-sotalol peaked about 3 h after oral administration and declined with a half-life of 7.9 9.7 h. The Cmax and AUC showed dose-related increases, while the urinary recovery as the unchanged form remained constant (66-68% of the dose). During repeated oral administration the plasma concentration of (+)-sotalol reached almost a steady state on the 3rd day and there was no change in renal clearance of (+) sotalol measured on the 1st, 4th and 7th days. After intravenous administration, (+)-sotalol in plasma decreased bi-exponentially with a terminal half-life of 7.6 8.3 h and the urinary recovery as unchanged drug amounted to 84-88% of the dose. The increase in QT interval was significant after a single oral administration except for the lowest dose, and regression analysis revealed a significant correlation between QTc interval and concentration of (+)-sotalol in plasma. The same correlation was evident with repeated oral doses on the 1st, 4th and 7th days. In the case of single intravenous administrations of (+)-sotalol, a combined pharmacokinetic-pharmacodynamic model was attempted by assuming an effect compartment.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7996392 TI - Decreased cyclosporin A absorption after treatment with GoLytely lavage solution in rats. AB - Recently we observed a case in which the cyclosporin A absorption decreased after treatment with GoLytely lavage solution in a kidney transplant patient. In this study, we confirmed the decrease of the blood concentration of cyclosporin A after oral administration by GoLytely (Macrogol 3350) based on experiments with rats. The peak blood cyclosporin A concentration, and the area under the blood drug concentration-time curve from 0 to 24 h in the GoLytely-administered group were significantly lower than the control group. In the case of gastrointestinal dysfunction such as diarrhoea, or in treatment with laxatives such as GoLytely lavage solution, whole blood cyclosporin levels must be carefully monitored, and intravenous cyclosporin A may be more suitable for providing adequate immunosuppression. PMID- 7996390 TI - Pharmacokinetic and pharmacodynamic studies of the histamine H1-receptor antagonist ebastine in dogs. AB - The pharmacokinetics and pharmacodynamics of ebastine at single oral doses of 10 and 20 mg were studied in six healthy beagle dogs. Plasma concentrations of the active metabolite of ebastine were measured at predetermined times after the dose. At these times an intradermal injection of 0.01 mL of a 0.2 mg mL-1 histamine diphosphate solution was given, and wheal areas were computed. The plasma elimination half-life of ebastine was 4.38 +/- 1.01 h after 10 mg ebastine and 4.09 +/- 0.74 h after 20 mg ebastine; the distribution volume was 3.99 +/- 0.88 and 3.65 +/- 0.75 L kg-1 after 10 and 20 mg of ebastine, respectively; the clearance after the 10 mg dose of ebastine was 0.67 +/- 0.24 L h-1 kg-1 and after 20 mg ebastine was 0.63 +/- 0.17 L h-1 kg-1. The mean histamine-induced wheal areas were significantly suppressed from 1 to 25 h after the 10 mg dose ebastine and from 1 to 32 h after the 20 mg dose ebastine, compared with the mean predose wheal areas (P < 0.001). Maximum suppression of the wheals was 75 and 82% from 10 and 20 mg ebastine, respectively. A combined pharmacokinetic-pharmacodynamic model was used to analyse the relationship between inhibition of wheal skin reaction and changes in the active metabolite of plasma concentration after ebastine administration. A significant delay of 3-4 h was present between the maximum effect and the peak plasma concentration. Calculated from mean data, the rate constant for equilibration of the drug between plasma and effect site was 0.17 and 0.22 h-1 after 10 and 20 mg ebastine with a half-life of 4.13 and 3.56 h, respectively, and the steady-state plasma concentration resulting in 50% of maximal effect was 18.9 +/- 4.8 ng mL-1 after 10 mg and 18.2 +/- 5.7 ng mL-1 after 20 mg ebastine. PMID- 7996393 TI - Enhanced rectal absorption of itazigrel formulated with polysorbate 80 micelle vehicle in rat: role of co-administered esterase. AB - We investigated the effect of esterase on rectal absorption in the rat of itazigrel using polysorbate 80 (PS-80) micelle as a vehicle to overcome the poor aqueous solubility of itazigrel. The itazigrel formulation prepared with PS-80 increased the absorption compared with a 0.25% carmellose sodium suspension, probably by supplying the itazigrel solute to keep a high concentration at the epithelial surface. When esterase was co-administered with the formulations containing PS-80, the absorption of itazigrel from rat rectum was accelerated further, by rapid release of itazigrel from the micelle vehicle after enzymatic degradation of the PS-80 micelle. PMID- 7996394 TI - Pharmacokinetics and brain distribution of zolpidem in the rat after acute and chronic administration. AB - The pharmacokinetics of zolpidem were studied after single dose, administered for either 7 or 28 days to rats. Thirty minutes after the last dose, animals were killed and the brain removed. The highest concentrations in plasma, which were observed at the first sampling time (0.5 h) were 2341 +/- 540 (day 0), 1956 +/- 325 (day 7) and 2908 +/- 1369 ng mL-1 (day 28). Corresponding AUC values of 1742 +/- 488, 1583 +/- 422 and 2683 +/- 1249 ng mL-1 h were found. MRT increased significantly from 0.46 +/- 0.06 h on day 0 to 0.67 +/- 0.02 h on day 28. The cerebral levels showed no significant change during the chronic administration (766 +/- 285, 685 +/- 171 and 887 +/- 264 ng g-1, respectively). No modification of the principal kinetic parameters was detected up to the 28th day of treatment. PMID- 7996395 TI - Pharmacokinetic behaviour in polymorphonuclear leucocytes of N,N dimethylcarbamoylmethyl alpha,2-dimethyl-5H-[1]benzopyrano[2,3-b]- pyridine-7 acetate (Y-23023), a new prodrug type of anti-inflammatory agent, and indomethacin after oral administrations in rats. AB - N,N-Dimethylcarbamoylmethyl alpha,2-dimethyl-5H-[1]- benzopyrano[2,3-b]pyridine-7 acetate (Y-23023) is a prodrug developed as a new non-steroidal anti-inflammatory drug (NSAID). Y-23023 is rapidly hydrolysed to an active metabolite, alpha,2 dimethyl-5H-[1]benzopyrano[2,3-b]pyridine-7-acetic acid (M1) following its absorption and then exhibits a strong anti-inflammatory activity. We have examined the pharmacokinetic behaviour in polymorphonuclear leucocytes (PMNs) of M1 and of indomethacin after oral administration to rats of Y-23023 and indomethacin, respectively. Y-23023 was rapidly absorbed, producing a mean Cmax (1.13 micrograms mL-1) of M1 after 1 h in plasma. Indomethacin was less rapidly absorbed, producing a mean Cmax (3.38 micrograms mL-1) after 3 h in plasma. The mean AUC of M1 and indomethacin in plasma were 5.45 micrograms h mL-1 and 22.49 micrograms h mL-1, respectively. The mean tmax, Cmax and AUC of M1 in PMNs were 1 h, 11.1 ng (41 pmol)/10(8) cells and 58.6 ng (164 pmol) h/10(8) cells, respectively. The same parameters for indomethacin in the PMNs were 3 h, 15.4 ng (57 pmol)/10(8) cells and 95.2 ng (266 pmol) h/10(8) cells, respectively. The PMNs/plasma ratio of M1 was about 2.8 times that of indomethacin. These results indicate that the association of M1, an active metabolite of Y-23023, from blood to the PMNs is greater than that of indomethacin. PMID- 7996396 TI - Loss of the TOL meta-cleavage pathway functions of Pseudomonas putida strain PaW1 (pWW0) during growth on toluene. AB - A derivative of Pseudomonas putida strain PaW1 bearing the TOL plasmid pWW0 was isolated from a culture which has grown unlimited on toluene. In contrast to the parent strain PaW1, the derivative, strain CG220, is unable to grow with xylenes and toluates, while toluene and benzoate served as substrates. Strain CG220 had a remarkable growth advantage against the wild type when grown with toluene. Biochemical analysis showed that in strain CG220 toluene was metabolised through the TOL plasmid upper pathway to benzoate and the latter to amphibolic intermediates by the chromosomal encoded ortho-cleavage pathway. No activities of the TOL plasmid encoded toluate dioxygenase and catechol 2,3-dioxygenase were detectable in strain CG220. No reversion of strain CG220 to growth with xylenes or toluates was observed. Hybridisation experiments with TOL plasmid-derived gene probes and oligonucleotides revealed that genes xylY to xylG were absent, while xylX and xylK were still present. PMID- 7996397 TI - Characterization of a Tn925-induced mutant of Staphylococcus aureus altered in exoprotein production. AB - An insertional mutant was isolated from a bovine Staphylococcus aureus strain after membrane-mating with a Streptococcus faecalis strain carrying conjugative plasmid pCF10::Tn925. This mutant, designated RC128, showed enhanced production of alpha-hemolysin and proteases and decreased production of coagulase, extracellular protein A, DNase, lipase and delta-hemolysin. No difference was found in the production of beta-hemolysin. Both, Southern blot analysis and transfer of the pleiotropic mutant phenotype by transduction, indicated that the mutation was originated from a single insertion of transposon Tn925. The LD50 determined by intraperitoneal administration in mice showed that mutant RC128 was slightly less virulent than its parental strain. PMID- 7996398 TI - Radiation sensitivities of Acinetobacter strains isolated from clinical sources. AB - For twelve clinical strains genetically grouped together with Acnetinobacter radioresistens FO-1T, the radiation sensitivity was measured. Their D10 values in gamma-ray irradiation under N2-equilibrium were 0.24 to 0.93 kGy and about 1/10 to 1/3 of that of the radiation-resistant strain FO-1. The results showed that the genospecies A. radioresistens contained some radiation-sensitive strains. PMID- 7996399 TI - The combined procedure for cataract and glaucoma. PMID- 7996400 TI - Photorefractive keratectomy after radial keratotomy. AB - We report the results of a prospective study that evaluated the efficacy, predictability, and safety of excimer laser photorefractive keratectomy (PRK) to correct residual myopia after radial keratotomy (RK). Using a 193 nm excimer laser, we performed PRK on ten undercorrected myopic eyes that had previous RK surgery. The mean interval between the RK and PRK was 1.5 years. Mean follow-up was seven months. Mean preoperative refraction was -4.08 +/- 1.35 diopters (D) and after PRK was +1.61 +/- 1.18 D at three months, +1.05 +/- 0.75 D at six months, and +0.79 +/- 0.83 D at 12 months. An uncorrected visual acuity of 20/40 or better was achieved in eight eyes at three months, seven eyes at six months, and three eyes at 12 months. One eye had a transient loss of two Snellen lines of best spectacle corrected visual acuity because of increased haze. No other significant complication was noted. Our study shows that PRK is a predictable, effective, stable, and safe technique to correct residual myopia after RK. The results were similar to those of PRK without prior surgery, although we noted a slightly greater hyperopic deviation. We believe that eyes undercorrected by RK may benefit from subsequent PRK. PMID- 7996401 TI - Videokeratographic evaluation of peripheral redeepening in the cadaver eye. AB - Radial incisions must be deep enough to correct myopia. As currently performed, most surgeons set their diamond blades at a constant depth and do not alter the blade length throughout the procedure. The cornea is not uniformly thick; the central cornea is the thinnest and it thickens toward the periphery. Therefore, an incision of constant depth would be deeper centrally and thinner peripherally. Peripheral redeepening of the cornea would in theory make the incision depth deeper throughout and should increase the effect of radial incisions. We reviewed the literature on this technique and performed radial incisional studies on the human cadaver eye using videokeratography to measure incision depth indirectly. Based on our studies, we believe that peripheral redeepening has no effect on central cornea flattening. PMID- 7996402 TI - Ultrasound biomicroscopy in refractive surgery. AB - The need for improved methods of assessing corneal topography arose from the advent of refractive surgery. Ultrasound biomicroscopy (UBM) is a high-resolution technique that uses high-frequency transducers to evaluate the cornea. We conducted a pilot study to assess the cornea after refractive surgery using UBM. Six patients who had prior epikeratophakia, radial keratotomy, or photorefractive keratectomy were examined with a 50 MHz transducer. Ultrasound biomicroscopy provided a striking image of the epigraft after epikeratophakia. Imaging after radial keratotomy and photorefractive keratectomy was less helpful. However, the corneal refractive power computed from the UBM data for the photorefractive keratectomy was close to the optical keratometry values. The study indicates UBM has some applications in analyzing the cornea after refractive surgery. PMID- 7996403 TI - Combined procedure for glaucoma and cataract: a retrospective study. AB - To ascertain the long-term effects of a triple procedure in the case of coexisting cataract and glaucoma, we did a retrospective study of 93 eyes that had cataract extraction, IOL implantation, and trabeculectomy within a ten-year period. Mean follow-up was 32.4 +/- 21.9 months. Mean postoperative intraocular pressure (IOP) was significantly lower than preoperatively, even though fewer medications were being used. One year after surgery, 60% of eyes had a best corrected visual acuity of 20/40 or better with an average improvement of 3.8 Snellen lines. Patients who had had surgery four or more years before the study had the highest percentage of eyes with an IOP exceeding 22 mm Hg. This group also had the poorest IOP control when no medications were used and when the patient took fewer medications than before surgery. The finding that IOP control decreases with postoperative time raises questions about the long-term success of the triple procedure in controlling IOP. PMID- 7996404 TI - Effect of two anterior capsulotomy techniques on the corneal endothelium. AB - We performed a prospective, randomized, clinical study to assess the effect of two anterior capsulotomy techniques on the corneal endothelium. Specular microscopy was done preoperatively and postoperatively in 57 patients having manual extracapsular cataract surgery with a can-opener capsulotomy or with a retained anterior capsule flap. The mean percentage of cell loss following the can-opener capsulotomy was 0.43 (P = .22). There was no statistically significant alteration in endothelial morphology after surgery. The cell loss with a retained anterior capsule flap was zero. However, there was a statistically significant difference in polymegathism (P = .024) and pleomorphism (P = .045) after surgery. A comparison of the two techniques showed no statistically significant difference in cell loss or in pleomorphism. The statistically significant difference in polymegathism (P = .01) was not clinically significant. Our findings indicate that, when carefully performed, both methods of anterior capsulotomy for manual extracapsular cataract surgery are safe for the corneal endothelium. PMID- 7996405 TI - Complications associated with endocapsular balloon implantation in rabbit eyes. AB - After phacoemulsifying the lens in six rabbit eyes through a 1.3 mm anterior capsule opening, we implanted a silicone balloon in the capsular bag and filled it with liquid silicone. The eyes were enucleated nine to 21 months postoperatively, embedded in paraffin, stained with toluidine blue, and examined by stereoscopic and light microscopy. We looked at the postoperative complications primarily. All balloons were securely fixated within the capsule. Surface wrinkles were observed in two balloons. The injected silicone remained transparent. None of the lens capsules was completely transparent, although all remained relatively clear. Retrocorneal membranes were produced in one eye in which the silicone leaked. PMID- 7996406 TI - Inhibition of proliferating lens epithelium with antitransferrin receptor immunotoxin. AB - We investigated the effect of an antitransferrin receptor immunotoxin (454A12 rRA) on proliferating human and baboon lens epithelium in vitro. Human and baboon lens epithelial cells grown in modified TC-199 medium at 35 degrees Celsius in 7% CO2 were seeded in 24 well plates at a density of 17,500 cells/ml to 40,000 cells/ml. The cells were exposed to various concentrations of 454A12-rRA for seven days. The sensitivity of proliferating human lens epithelium to 454A12-rRA was dependent on the dose, with a 60% to 70% reduction in cell counts at immunotoxin concentrations of 100 ng/ml and above. The immunotoxin had no significant effect on baboon lens epithelium in vitro, which suggests that it is specific for human tissue. By preventing the proliferation of human lens epithelial cells, immunotoxin 454A12-rRA may be useful in the management of posterior capsule opacification after planned extracapsular cataract surgery. PMID- 7996407 TI - Evaluating surgically induced astigmatism. AB - Using a modification of vector analysis for calculating surgically induced astigmatism, we describe a simple method that divides the induced cylinder into two orthogonal components. This decomposition allows with-the-rule and against the-rule astigmatic changes to be calculated for individual case analysis, as well as for statistical analysis of aggregate data. Because it is based on the true induced cylinder, as determined by optical principles, this method overcomes some of the problems associated with earlier methods of evaluating surgically induced astigmatism. PMID- 7996408 TI - Toric intraocular lenses: correcting astigmatism while controlling axis shift. AB - We evaluated the efficacy of toric intraocular lenses (IOLs) implanted in the eyes of 47 patients who had preoperative against-the -rule astigmatism. The lenses, which had a cylinder power of 2.00 diopters (D) (n = 26) or 3.00 D (n = 21), were implanted through a 5.7 mm incision after cataract extraction by phacoemulsification. Best corrected visual acuity three months postoperatively was 20/25 or better in 77% of eyes. The 3.00 D IOLs resulted in better correction than the 2.00 D IOLs when the axis shift of the lens was less than 30 degrees. A negative effect occurred in some eyes in which the lens axis rotated more than 30 degrees. The maximum acceptable axis shift seems to be less than 30 degrees. PMID- 7996409 TI - Neodymium:YAG laser damage on silicone intraocular lenses. A comparison of lesions on explanted lenses and experimentally produced lesions. AB - In this study we examined 17 explanted silicone intraocular lenses (IOLs) (two one-piece, 15 three-piece) that had evidence of neodymium:YAG (Nd:YAG) laser damage. The majority of lenses (47.1%) had been explanted because of persistent pigment deposits and chronic inflammation. Decentration or IOL dislocation had occurred with 29.4% of lenses. All 17 patients had had Nd:YAG laser posterior capsulectomy, anterior surface polishing, or both; treatments ranged from one to 13 times. By both clinical and gross examination, the laser lesions appeared dark. This was misinterpreted by some opthalmologists as pigment deposits and some patients had additional Nd:YAG laser treatment, which increased the severity of the laser damage. The mean depth of laser damage on the IOLs was 143 +/- 113.4 microns. It was between 51 and 175 microns in approximately 61.0% and deeper than 300 microns (maximum 660 microns) in 9.3%. We compared the explanted IOLs with silicone IOLs that were experimentally damaged using standard power levels from 0.3 to 3.0 mJ and different focal areas. The appearance of the experimentally induced laser burns was equivalent to that on the explanted IOLs, especially the dark laser pits. Since the laser lesions may resemble pigment deposits on slitlamp examination, we recommend careful examination of patients prior to planned laser therapy. PMID- 7996410 TI - No-stitch, small incision cataract surgery with flexible intraocular lens implantation. AB - Small incision cataract surgery has several advantages over conventional surgery, including faster postoperative visual rehabilitation. We evaluated 100 consecutive cases of no-stitch, small incision surgery with a square sclerocorneal tunnel and a flexible intraocular lens. Permanent self-sealing of the wound seemed to increase intraoperative safety considerably. With the specific incision used, corneal trauma and irrigation fluid outflow were minimal. Refraction and K-readings stabilized within the first postoperative week, which is when most eyes attained best final visual acuity. No early peak or protracted drift of astigmatism occurred. Minimally leaking wounds in three eyes were left unsutured; a transient filtering bleb was observed in two of these eyes after resorption of an intracameral air bubble. Our results support the theoretical concept and justify the use of no-stitch, small incision surgery. PMID- 7996411 TI - Heparin-surface-modified intraocular lens implantation in eyes with pseudoexfoliation syndrome. AB - Eyes with pseudoexfoliation syndrome have a greater risk of intraoperative and postoperative complications. Clinical and histopathological studies indicate that heparin-surface-modified intraocular lenses (HSM IOLs) can reduce postoperative anterior segment inflammation. Our study evaluated the blood-aqueous barrier permeability in eyes with pseudoexfoliation syndrome and implanted with an HSM IOL. We examined two groups of 20 patients, one comprising patients with pseudoexfoliation syndrome and one a sex- and age-matched control group with senile cataracts. Each group was divided into two subgroups of ten patients each. In one subgroup, an HSM IOL was implanted; in the other, a conventional poly(methyl methacrylate) IOL. We performed a complete ophthalmologic examination and iris angiography preoperatively and at 30, 90, and 180 days after surgery. Fluorophotometry was performed at the 90-day and 180-day postoperative examinations. The patients with pseudoexfoliation syndrome had a higher blood aqueous barrier permeability than did the control group. Permeability decreased significantly three and six months after surgery, especially in the HSM IOL group. PMID- 7996412 TI - Heparin-surface-modified intraocular lens implantation in patients with glaucoma, diabetes, or uveitis. AB - We investigated the clinical outcome in two groups of patients who had an extracapsular cataract extraction and implantation of a heparin-surface-modified intraocular lens (HSM IOL) (Group 1) or a conventional poly(methyl methacrylate) (PMMA) lens (Group 2). Nineteen patients in Group 1 had bilateral cataract extraction with implantation of an HSM IOL in one eye and a conventional lens in the fellow eye. All patients had glaucoma, diabetes, or uveitis. Over the long term, there was no statistically significant difference between groups in visual acuity, corneal edema, anterior chamber reaction, and amount of posterior synechia formation and IOL deposits. Yet short-term clinical evaluation revealed significantly less reaction in eyes with the HSM IOL than in those with the PMMA lens. In patients with both lens types implanted, early postoperative anterior chamber reaction was less and IOL deposits fewer in the eye with the HSM IOL. PMID- 7996413 TI - Ultrasound velocities for axial eye length measurement. AB - Since 1974, I have used individual sound velocities for each eye condition encountered for axial length measurement. The calculation results in 1,555 M/sec for the average phakic eye. A slower speed of 1,549 M/sec was found for an extremely long (30 mm) eye and a higher speed of 1,561 M/sec was noted for an extremely short (20 mm) eye. This inversely proportional velocity change can best be adjusted for by measuring the phakic eye at 1,532 M/sec and correcting the result by dividing the square of the measured axial length (AL1,532)2 by the difference of the measured axial length (AL1,532) minus 0.35 mm. A velocity of 1,534 M/sec was found for all aphakic eyes regardless of their length, and correction is clinically significant. The velocity of an eye containing a poly(methyl methacrylate) intraocular lens is not different from an average phakic eye but it does magnify the effect of axial length change. I recommend measuring the pseudophakic eye at 1,532 M/sec and adding to the result (AL1,532), + 0.04 + 44% of the IOL thickness. The speed for an eye with a silicone IOL was found to be 1,476 M/sec (or AL1,532 + 0.04 - 56% of IOL thickness) and for glass, 1,549 M/sec (or AL1,532 + 0.04 + 75% of IOL thickness). A speed of 1,139 M/sec was found for a phakic eye with silicone oil filling most of the vitreous cavity and 1,052 M/sec for an aphakic eye filled with oil. For varying volumes of oil, each eye should be calculated individually. The speed was 534 M/sec for phakic eyes filled with gas. Eyes containing a silicone IOL or oil or gas will create clinically significant errors (3 to 10 diopters) if the sound velocity is not corrected. PMID- 7996414 TI - Aqueous misdirection syndrome: a complication of neodymium: YAG posterior capsulotomy. AB - A 50-year-old, white, pseudophakic man who had a neodymium:YAG (Nd:YAG) posterior capsulotomy for capsule opacification developed a persistent rise in intraocular pressure (IOP) associated with a flat anterior chamber. Full-thickness patent iridotomy performed with an Nd:YAG laser did not reduce IOP. A-scan ultrasonography showed aqueous pockets in the vitreous, leading to a diagnosis of malignant glaucoma. Medical therapy comprising atropine, phenylephrine, mannitol, and acetazolamide normalized IOP and resolved the clinical findings. PMID- 7996415 TI - Stop and chop phacoemulsification. AB - We present a method for phacoemulsification within the capsular bag in which sculpting is performed to provide space for nuclear manipulation and then the posterior plate is cracked into two halves. The nuclear rim is chopped into bite size pieces for removal using a modified lens hook that is buried in the nuclear periphery and pulled toward the center. The procedure begins as a routine nuclear cracking technique and then stops. It continues as a chop technique. PMID- 7996416 TI - Consultation section. Phacoemulsification complicated by posterior capsule, rupture, vitreous loss, and posterior dislocation of a small nuclear chip. PMID- 7996417 TI - Role of endogenous cholecystokinin in the facilitation of mu-mediated antinociception by delta-opioid agonists. AB - Published results suggest that delta-opioid agonists can modulate the mu-mediated analgesia. In this work, the antinociceptive effects produced by the mu agonist [D-Ala2,NMe-Phe4,Gly-ol5]enkephalin or the mixed inhibitor of enkephalin degrading enzymes RB 101 (N- [(R,S)-2-benzyl-3[(S)(2-amino-4-methyl- thio)butyldithio]-1-oxopropyl]-L-phenylalanine benzyl ester) were studied after administration of the systemically active and selective delta agonist Tyr-D-Ser(O tert-butyl)-Gly-Phe-Leu- Thr(O-tert-butyl). In the hot-plate test in mice, Tyr-D Ser(O-tert-butyl)-Gly- Phe-Leu-Thr(O-tert-butyl) (i.v.) potentiated the antinociceptive responses elicited by [D-Ala2,NMe-Phe4,Gly-ol5]enkephalin (i.v.) or RB 101 (i.v.). These facilitatory effects were reversed not only by prior administration of the delta-selective antagonist naltrindole (0.5 mg/kg s.c.), but also unexpectedly by the selective cholecystokinin CCK-A antagonist MK-329 (20 micrograms/kg i.p.). In addition, the CCK analog [Boc- Tyr(SO3H)-Nle-Gly-Trp Nle-Asp-Phe-NH2] (a mixed CCK-A/CCK-B agonist) increased the jump latency and this effect was blocked by MK-329 (20 micrograms/kg i.p.) and by naloxone, but not by the selective CCK-B antagonist L-365,260 (5 mg/kg i.p.). In contrast, the selective CCK-B agonist BC 264 (62 micrograms/kg i.v.) produced a hyperalgesic effect that was antagonized by L-365,260 (5 mg/kg i.p.). Taken together, these findings suggest that the potentiating effects of delta agonists on mu-mediated analgesia are due to an increase in the release of endogenous CCK interacting with CCK-A and CCK-B receptors and resulting in positive and negative regulation of the endogenous opioid system.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7996418 TI - Chronic nicotine administration does not affect peripheral vascular reactivity in the rat. AB - The effect of chronic nicotine exposure on vascular function and neurotransmitter content was studied in the Fisher 344 rat. Implantation of osmotic mini pumps containing nicotine (0.18-4.7 mg/kg/day) for 14 days resulted in dose-related levels of plasma nicotine (up to 362 +/- 15 ng/ml) and its major metabolite cotinine (1545 +/- 40 ng/ml), as measured by gas chromatography. Rat body weight increase was inhibited significantly by 4.7 mg/kg/day of nicotine exposure. In the isolated perfused mesentery, transmural nerve stimulation of capsaicin sensitive sensory nerves produced vasodilator responses that were not different between vehicle- and chronic nicotine-treated animals. Endothelium-dependent vasodilation elicited by acetyl-choline also was not influenced by chronic nicotine treatment. Furthermore, chronic nicotine exposure in vivo had no effect on in vitro vasodilator responses caused by nicotine itself, either at low (3 x 10(-5) M) or high (3 x 10(-4) M) concentrations. In tail artery ring segments, vasoconstrictor responses to either transmural adrenergic nerve stimulation or norepinephrine were not different when vehicle and nicotine treatment groups were compared. Prior chronic nicotine exposure also did not alter nicotine's ability to relax ring segments that were precontracted with norepinephrine. Vascular contents of norepinephrine, calcitonin gene-related peptide, neuropeptide Y and substance P were not altered by chronic nicotine treatment. In conclusion, although nicotine has direct vascular actions, chronic nicotine exposure up to 4.7 mg/kg/day does not significantly alter vascular reactivity. PMID- 7996420 TI - Acute effects of ethanol on cardiac output and its derivatives in spontaneously hypertensive and normotensive rats. AB - This study investigated the influence of small to moderate doses of ethanol on arterial pressure (MAP), heart rate, cardiac index (CI), stroke volume (SV) and total peripheral resistance (TPR) of anesthetized spontaneously hypertensive rats (SHRs) and two age-matched normotensive strains, Wistar Kyoto (WKY) and Sprague Dawley (SD) rats. Compared with WKY values, the significantly higher MAP of SHRs (175 +/- 4 vs. 118 +/- 4 mm Hg) was the result of a significantly elevated TPR (6.1 +/- 0.3 vs. 3.1 +/- 0.2 mm Hg/ml/min/100 g; P < .05), because Cl was significantly lower (31 +/- 1.6 vs. 41 +/- 2.5 ml/min/100 g; P < .05). A lower SV (261 +/- 13 vs. 394 +/- 20 microliters/min; P < .05) accounted for the reduced Cl in SHRs, because HR was similar (318 +/- 4 vs. 328 +/- 11 beats/min). In spite of similar MAP (114 +/- 3.9 vs. 118 +/- 4 mm Hg) of SD and WKY rats, Cl was significantly higher (33 +/- 2 vs. 41 +/- 2.5 ml/min/100 g; P < .05) due to a higher SV (339 +/- 19 vs. 394 +/- 20 microliters/min; P < .05) and TPR was significantly lower (3.7 +/- 0.2 vs. 3.1 +/- 0.2 mm Hg/ml/min/100 g; P < .05) in the latter strain. Low dose ethanol (0.1-0.25 g/kg) had no effect, whereas a moderate dose of 0.5 g/kg elicited strain-dependent hemodynamic responses which comprised significant increases in Cl and SV in normotensive rats, but not in SHRs. However, because of a reduction in TPR, MAP did not change.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7996419 TI - Cyclic GMP potentiation by WIN 58237, a novel cyclic nucleotide phosphodiesterase inhibitor. AB - The objectives of this study were to determine the potency and selectivity of the structurally novel cyclic nucleotide phosphodiesterase (PDE) inhibitor, WIN 58237 (1-cyclopentyl-3-methyl-6-(4- pyridyl)pyrazolo[3,4-d]pyrimidin-4-(5H)-one), and to determine if this compound possesses cyclic GMP (cGMP) PDE inhibitory activity in vitro and in vivo. WIN 58237 is a competitive inhibitor of cGMP PDE V from canine aorta, with a Ki value of 170 nM. It is a relatively less potent inhibitor of calmodulin-sensitive PDE I and cGMP-inhibitable cyclic AMP PDE III; but does inhibit cyclic AMP PDE IV with an IC50 value of approximately 300 nM. In vitro, WIN 58237 is a functional cGMP PDE inhibitor at submicromolar concentrations as evident by potentiation of both sodium nitroprusside- and atrial natriuretic factor-mediated vasorelaxation of contracted, endothelial-denuded rat aortic rings. Moreover, WIN 58237 possesses vasorelaxant activity in the presence of an intact endothelium or nitric oxide. Similar results are evident in vivo, as WIN 58237 (0.3-3.0 mg/kg i.v.) decreases mean arterial pressure in conscious spontaneously hypertensive rats with an associated increase in vascular (aortic) cGMP content in vivo. Both the decrease in mean arterial blood pressure and increase in aortic cGMP content are attenuated by the nitric oxide synthase inhibitor, N omega-nitro-l-arginine. However, WIN 58237 may possess an additional depressor mechanism of action. WIN 58237 restores vasorelaxation responsiveness to nitroglycerin in vitro and in vivo in models of vascular tolerance.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7996421 TI - Isoflurane reduces Ca++ channel current and accelerates current decay in guinea pig portal vein smooth muscle cells. AB - The volatile anesthetic isoflurane (ISO) can exert significant inhibitory effects on hemodynamics and organ perfusion. It was hypothesized that venodilation during ISO exposure was mediated through a reduction in inward Ca++ channel current. By using the whole cell mode of single cell patch clamp technique, the action of ISO on L-type Ca++ channel current was examined. ISO caused a concentration-dependent reduction in maximal Ca++ channel current and shifted the current activation to more negative potentials. ISO, 3%, shifted the voltage for half-maximal channel inactivation from -21.9 to -33.4 mV. Measurement of time constants for inward current activation and inactivation revealed that the inactivation phase exhibited a concentration-dependent reduction over the range of 0.36 to 3% ISO. The decrease in the inactivation time constant is consistent with accelerated inactivation of the L-channel current. Estimated binding constants for ISO to resting or inactivated channels suggest absence of state-dependent inhibition of channel conductance. The venodilatory effects of ISO are due in part to limitation of Ca++ influx which may secondarily affect Ca(++)-dependent mechanisms such as the outward Ca(++)-activated K+ channel population. Reduction in current by ISO may occur through receptor-independent mechanisms and may involve perturbation of the sarcolemmal lipid bilayer. PMID- 7996422 TI - Suppression of human eosinophil respiratory burst and cyclic AMP hydrolysis by inhibitors of type IV phosphodiesterase: interaction with the beta adrenoceptor agonist albuterol. AB - The cyclic AMP phosphodiesterase (PDE) III/IV inhibitor, zardaverine, and the PDE IV-selective inhibitor, rolipram, both caused concentration-dependent inhibition of opsonized zymosan-stimulated superoxide anion generation by purified human peripheral blood eosinophils with approximate IC50 values of 30 and 40 microM, respectively. In contrast, the selective PDE III inhibitor, SK&F 94120, was ineffective in suppressing this functional response at concentrations below 100 microM. The inhibitory effects of rolipram and zardaverine on superoxide anion generation were increased in the presence of the beta-2 adrenoceptor agonist, albuterol, which itself was an inhibitor of eosinophil respiratory burst (IC50 = 20 microM). The effects of albuterol and the PDE inhibitors in combination were simply additive. Paradoxically, both rolipram and zardaverine significantly potentiated albuterol-induced cyclic AMP accumulation in a synergic fashion. Cyclic AMP PDE activity of eosinophil homogenates was inhibited by both zardaverine (IC50 = 515 nM) and rolipram (IC50 = 550 nM) as well as two other PDE IV-selective inhibitors, Ro 20-1724 (IC50 = 3.0 microM) and denbufylline (IC50 = 360 nM), whereas SK&F 94120 was ineffective. These data suggest that cyclic AMP levels in human eosinophils are regulated by the action of a type IV PDE isoenzyme and that elevation of the intracellular cyclic AMP concentration by PDE IV inhibition can suppress the functional activity of these cells. However, the suppressor effect of the PDE IV inhibitors appears to be independent of that of a beta-2 adrenoceptor agonist, implying a possible adenylyl cyclase-independent mechanism of action for beta agonists in eosinophils. PMID- 7996423 TI - Ethanol-induced depressions of cerebellar Purkinje neurons are potentiated by beta-adrenergic mechanisms in rat brain. AB - Electrophysiological studies indicate that EtOH decreases the firing rate of cerebellar Purkinje neurons in vivo and in vitro through a GABAA mechanism. These neurons receive a prominent noradrenergic input from the locus coeruleus. Stimulation of the locus coeruleus or local application of beta-adrenergic agonists potentiates Purkinje neuron responses to GABA and sensitizes GABA responses to the potentiative effects of EtOH. In the present study, we found that the modulatory influences of the beta-adrenergic agonist isoproterenol potentiated EtOH-induced depressions of Purkinje neuron firing. This isoproterenol interaction with EtOH was antagonized by the beta-adrenergic antagonist timolol. We found evidence that endogenous catecholamines can cause this effect as well. Timolol antagonized EtOH-induced depressions on 20% of the neurons studied. This was the same frequency as that previously found for EtOH induced potentiations of GABA depressions in this brain area. These data suggest that the Purkinje neurons showing this interaction receive spontaneously active catecholamine inputs that sensitize the GABA effects to the potentiative effects of ethanol. Consistent with this hypothesis, we also found that timolol antagonized this GABA/EtOH interaction. Taken together, these results are consistent with the hypothesis that EtOH-induced depressions of Purkinje neurons involved endogenous GABA actions that may be regulated by beta-adrenergic mechanisms. PMID- 7996424 TI - Evidence that systemically administered dopamine antagonists activate dopamine neuron firing primarily by blockade of somatodendritic autoreceptors. AB - Systemic administration of dopamine antagonists increases the activity of some dopamine neurons in the substantia nigra, and this effect is thought to occur through two potential mechanisms: 1) local blockade of dopamine acting at somatodendritic autoreceptors or 2) blockade of receptors on postsynaptic targets in the striatum, resulting in long-loop feedback modulation. Several studies have provided evidence that the major influence is via striatonigral feedback. In this study, we tested the latter model by comparing the actions of systemically administered dopamine antagonists on dopamine neuron activation after removing striatonigral feedback. Systemic administration of either haloperidol or of the dopamine D2-specific antagonist sulpiride caused significant increases in the firing rate of many dopamine neurons recorded both in intact rats and in rats with hemisection of the striatonigral projection. Dopamine cells recorded in hemisected rats did not show consistent differences in either the proportion of cells excited or in the magnitude of the excitation produced by antagonist administration. The magnitude of dopamine cell excitation occurring with antagonist administration was dependent on the spontaneous firing rate of the recorded cell, with slow-firing neurons generally exhibiting the largest excitatory responses. These results provide evidence that blockade of dopamine neurons in the striatum is not the primary mechanism by which systemically administered dopamine antagonists excite dopamine neurons. Thus, dopamine antagonists most likely increase dopamine cell firing rate by blockade of somatodendritic autoreceptors, suggesting that the basal activity of the cells is dependent in part on dendritically released dopamine within the substantia nigra. PMID- 7996425 TI - Haloperidol-induced behavioral supersensitivity is increased by monosialoganglioside treatment in rats without affecting spiroperidol-binding. AB - In rats, dopamine supersensitivity was induced by haloperidol (HAL) treatment for 3 weeks, either by implanted polymer matrices or by daily i.p. injections (1.0 mg/kg/day). Thereafter, dopamine supersensitivity was tested by measurement of motor activity of the animals after application of the dopamine agonist apomorphine (0.5 mg/kg i.p.) and by determination of the specific D2 dopamine binding sites in the corpus striatum by using [3H]spiroperidol. In both modes of HAL administration, no differences were found in the behavioral and neurochemical parameters. The apomorphine-induced motility was enhanced, and the known up regulation of the striatal D2 dopamine binding was detected. When monosialoganglioside (GM1) was given daily i.p. for 3 weeks parallel to HAL application, dopamine supersensitivity, as indicated by the apomorphine-induced motility, was enhanced significantly without affecting the striatal D2 dopamine receptor up-regulation. In a subsequent experiment, we reduced the HAL dose and observed the expected D2 dopamine up-regulation. However, GM1 had no effect either on striatal D2 dopamine binding or on motility. A thin-layer chromatography analysis revealed that the endogenous gangliosides pattern in the corpus striatum also remained unchanged after HAL treatment. In conclusion, GM1 induced elevation of behavioral supersensitivity cannot be explained by a direct interaction with the D2 dopamine receptor, but other mechanisms may be involved, such as the modification of second messenger pathways. PMID- 7996426 TI - Blood-brain barrier permeability and in vivo activity of partial agonists of benzodiazepine receptor: a study of L-663,581 and its metabolites in rats. AB - L-663,581 [FG 8205; 7-chloro-4,5-dihydro-5-methyl-3-(5-(1-methylethyl)- 1,2,4 oxadiazol-3-yl)6H-imidazo(1,5-A)(1.4)-benzodiazepine-6-one] is an investigational partial agonist of benzodiazepine receptors for possible application in the treatment of anxiety. Previous studies have shown that the drug is eliminated mainly by biotransformation in rats, dogs and monkeys. Two metabolites, mono- and bis-hydroxy analogs were demonstrated to be active in vitro. The potency of benzodiazepine receptor binding (Ki) is 3.7 nM for the parent drug, 3.3 nM for the mono-hydroxylated metabolite and 1.2 nM for the bishydroxylated metabolite, respectively. Although the metabolites are as potent as, or more so than the parent drug in vitro, they are inactive in rats in a conditioned emotional response model. This study was designed to explore the underlying mechanisms responsible for the discrepancy between in vitro and in vivo activity of the metabolites. After i.v. administration of L-663,581 or its preformed metabolites, the metabolites were cleared more slowly than the parent drug. After i.p. administration at the same dose, the areas under the curve of the metabolites were 2 to 5 times that of the parent drug. Thus, the lack of in vivo activity of the metabolites cannot be explained by the absorption and/or elimination kinetics. Brain uptake studies indicated that the permeability of the blood-brain barrier is high for L-663,581 but very poor for the metabolites; the brain extraction ratio was about 0.6 for L-663,581 and less than 0.03 for the metabolites.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7996427 TI - Cyclic GMP but not cyclic AMP prevents renal platelet accumulation after ischemia reperfusion in anesthetized rats. AB - Platelets have been implicated in the pathophysiology of ischemia-reperfusion injury. In this study, antiplatelet effects of cyclic GMP (cGMP)- and cyclic AMP (cAMP)-mediated agents were evaluated in renal ischemia in pentobarbital anesthetized rats. Renal ischemia was induced by unilateral occlusion of the left renal artery (40 min) followed by reperfusion (30 min) with the contralateral kidney serving as control. 111Indium-labeled platelets, drugs or vehicle were administered 30 min before induction of renal ischemia. Occlusion of the left renal artery for 20, 40 or 60 min resulted in a 100, 300 and 600% increase (over contralateral right kidney) in the platelet-associated 111indium activity in the ischemic kidney. In all subsequent studies the kidney was occluded for 40 min to test the antiplatelet activity of individual agents. 8-Br-cGMP (0.1 and 0.3 mg/kg/min i.v.), zaprinast (0.1 mg/kg/min i.v.) and sodium nitroprusside (0.003 and 0.01 mg/kg/min i.v.) significantly attenuated platelet accumulation in renal ischemia, whereas 8-Br-cAMP (0.3 mg/kg/min i.v.) or milrinone (0.1 mg/kg i.v. bolus, plus 0.01 mg/kg/min) did not. Minoxidil (0.01 and 0.03 mg/kg/min i.v.), a vasodilator which produced equihypotensive effects as the cGMP-mediated agents, and milrinone failed to prevent platelet accumulation. These results demonstrate that modulation of the platelet function by cGMP agents can be dissociated from their blood pressure lowering effects. cGMP is known to inhibit both platelet adhesion and aggregation, whereas cAMP is only active against aggregation. The present findings provide further evidence that cGMP-mediated drugs may afford effective antiplatelet action in an in vivo model of ischemia-reperfusion injury. PMID- 7996428 TI - Electrophysiological and radioligand binding studies of elgodipine and derivatives in portal vein myocytes. AB - The effects of a novel dihydropyridine, elgodipine, and of three derivatives have been studied on the calcium channel currents of isolated cells from rat portal vein by the patch-clamp technique, and on specific (+)-[3H]isradipine binding to vascular membranes. Elgodipine inhibited both T- and L-type calcium channels in a concentration-dependent manner. Half-inhibitions of T- and L-type calcium channel current were obtained at concentrations of 32 and 2.3 nM, respectively. Currents activated repetitively were similarly inhibited than those after a rest period, indicating absence of use-dependent inhibition by elgodipine. When cells were held at depolarized membrane potentials at which T- or L-type calcium channels were inactivated, the inhibitory effects of elgodipine were enhanced on both calcium channel currents, indicating that the elgodipine-induced inhibition was voltage-dependent. The elgodipine concentration which blocked the inactivated calcium channels were 5 to 7 times lower than those which blocked the resting calcium channels. The inhibition constant for elgodipine obtained from the displacement of (+)-[3H]isradipine binding to the L-type calcium channels in vascular membranes was identical to the dissociation constant calculated from electrophysiological data on inactivated calcium channels. At concentrations that completely inhibited calcium channels, elgodipine had no effect on chloride and potassium channels, and did not interfere with the intracellular calcium stores.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7996430 TI - Inhibition by nickel of endothelin-1-induced tension and associated 45Ca movements in rabbit aorta. AB - Contractions induced by 10 nM endothelin-1 (ET) in the rabbit aortic media intimal layer were inhibited by prior exposure to 100 microM Ni++ (33.1%) or to a Ca(++)-free buffer (80.2%) but were unaffected by pretreatment with 0.1 microM nifedipine. Contractions elicited by phenylephrine (1 nM-100 microM) or K+ (10-50 mM) were not inhibited by 100 microM Ni++ but those induced by ET in tissues submaximally precontracted with 20 mM K+ were selectively antagonized by the divalent cation. The mechanism for the inhibitory action of Ni++ was ascertained by an examination of the effects of the cation on ET-induced alterations in the cellular distribution and mobilization of Ca++. Efflux of 45Ca from the muscle into a solution without added Ca++ was not altered by ET. Total or cellular 45Ca uptake (uptake after exposure to La and low temperature), at either low- or high affinity sites in resting muscles was also not affected by the peptide. However, low-affinity cellular 45Ca retention in muscles depolarized with high K+ levels (160 mM) was significantly enhanced (45.1%) by ET. Ni++ did not alter 45Ca retention in control and K(+)-treated muscles but it blocked the additional incremental 45Ca uptake associated with ET (in the presence of high K+). Thus, Ni++ produced a selective blockade of an ET-activated Ca++ influx pathway, distinct from the dihydropyridine-sensitive L-type Ca++ channels, in rabbit aortic smooth muscle. This action by Ni++ apparently inhibits subsequent contractile responses of the muscle to ET. PMID- 7996429 TI - GBR12909 attenuates cocaine-induced activation of mesolimbic dopamine neurons in the rat. AB - Previous studies have shown that the dopamine (DA) reuptake inhibitor 1-(2-[bis(4 fluorophenyl)-[methoxy]ethyl)-4-(3-phenylpropyl) piperazine (GBR12909) antagonizes the increase in extracellular DA evoked by local perfusion of cocaine into the striatum. In the present work, in vivo microdialysis methods were used to examine the effects of i.v. cocaine, GBR12909 and combinations of the two drugs on DA overflow in the nucleus accumbens of awake rats. Both cocaine and GBR12909 (0.3, 1.0 and 3.0 mg/kg) caused dose-related elevations in extracellular DA when given alone. However, the temporal profile of DA overflow was different with each drug. Cocaine caused a rapid and short-lived increase in DA, whereas GBR12909 caused a slow and sustained elevation of transmitter. In drug combination studies, the rise in extracellular DA after a modest dose of cocaine (1.0 mg/kg) was significantly reduced from 250% to 175% of baseline by pretreatment with a subthreshold dose of GBR12909 (0.3 mg/kg). A high dose of cocaine (3.0 mg/kg) increased dialysate DA by 600%; this rise in DA was decreased to 450% and 325% of baseline by pretreatment with 0.3 and 1.0 mg/kg of GBR12909, respectively. The neurochemical effect of the combination of GBR12909 plus cocaine was clearly not additive. GBR12909 also blocked the DA-releasing action of amphetamine (1.0 mg/kg). Our findings show that GBR12909 antagonizes the rise in extracellular DA produced by systemic cocaine and these results provide further evidence that DA reuptake inhibitors may be useful pharmacological adjuncts in the treatment of cocaine addiction and withdrawal in human patients. PMID- 7996431 TI - Characterization of alpha-1 adrenoceptor subtypes in human and canine prostate membranes. AB - Experiments were designed to characterize the predominant subtype of alpha-1 adrenoceptors in human and canine prostate tissue. The chemical (+/-)-beta ([125I]iodo-4-hydroxyphenyl)-ethyl- aminomethyl-tetralone bound in a specific, saturable manner to a single class of binding sites in membranes that expressed recombinant hamster alpha-1B, bovine alpha-1C and rat alpha-1D receptors expressed in rat-1 fibroblasts and to those from prostate tissue. Competition assays with human and canine prostate membranes revealed only a single class of binding sites. Binding affinity in both human and canine prostate most significantly correlated with binding affinity for the recombinant bovine alpha 1C receptor (r = .98 human, .95 canine). Further analysis with leverage plots demonstrated that binding affinity in human and canine prostate tissue is best predicted by binding affinity to recombinant bovine alpha-1C (P < .01 human and P < .001 canine). These data are consistent with a single class of alpha-1 adrenoceptors in human and canine prostate tissue, which is best represented as the alpha-1C subtype. PMID- 7996432 TI - Maternal and fetal brain and plasma levels of cocaine and benzoylecgonine after acute or chronic maternal intravenous administration of cocaine. AB - The effect of repeated i.v. administration of cocaine HCl (1.5, 3 or 6 mg/kg daily) from gestational day 8 through gestational day 18 was studied on maternal and litter parameters in the pregnant female Sprague-Dawley rat. These doses of cocaine had no significant effect on maternal weight gain or nutritional intake and did not significantly affect litter size. Levels of cocaine and its metabolite benzoylecgonine in the brain and plasma of the dams and their fetuses were measured on gestational day 18 at 1, 5, 20 or 60 min after a single injection or 11 daily i.v. injections of cocaine (6 mg/kg). The shape of the time courses for cocaine differed somewhat between dams and fetuses, with fetal plasma concentrations of cocaine initially being lower than those of their dams and then by 5 min becoming equivalent to those of their dams. Although plasma concentrations of cocaine soon equilibrated between dams and fetuses, plasma concentrations of benzoylecgonine did not. Interestingly, brain concentrations of cocaine did not differ between dams and fetuses. The most remarkable finding was that the relative distribution of cocaine between brain and plasma differed after chronic vs. acute treatment, with a relative shift in the distribution of cocaine from plasma to the brain in the fetuses, and with the exception of the earliest time point measured, in the dams after repeated dosing. PMID- 7996433 TI - Differential receptor reserve for 5-HT1A receptor-mediated regulation of plasma neuroendocrine hormones. AB - Treatment of rats with the serotonin 5-HT1A agonist 8-hydroxy-2-(di-n- propylamino)tetralin (8-OH-DPAT, 1 mg/kg s.c.) markedly elevated plasma levels of corticosterone (CORT), adrenocorticotropic hormone (ACTH) and prolactin (PRL); the levels of growth hormone were unaffected. Pretreatment with the irreversible receptor antagonist N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline (EEDQ, 6 mg/kg s.c.) greatly attenuated the increase in plasma CORT produced by 8-OH-DPAT (0.3 mg/kg s.c.). Prevention of EEDQ-induced 5-HT1A receptor inactivation by prior treatment with the reversible mixed 5-HT1A/beta-adrenergic antagonist (+/ )pinodolol (30 mg/kg s.c.) blocked the reduction of the CORT response to 8-OH DPAT. In contrast, prevention of EEDQ-induced inactivation of 5-HT2, alpha-1- and alpha-2-adrenergic and D1 and D2 dopamine receptors by a cocktail of selective antagonists of these receptors did not block the attenuation of the CORT response to 8-OH-DPAT. Dose-response curves were obtained for 8-OH-DPAT (0.01-3 mg/kg s.c.)-induced elevation of plasma CORT, ACTH and PRL after treatment (24 hr earlier) with vehicle or EEDQ (6 mg/kg s.c.) and analyzed for the extent of receptor reserve. Whereas substantial receptor reserves were observed for the 8 OH-DPAT rise in plasma CORT (80%) and ACTH (50%), no receptor reserve was seen for the increase in plasma PRL. The results are discussed with regard to potential differences in the receptors, G proteins, effectors and/or stoichiometric relationships between these components of the signal transduction pathway, leading to elevation of these plasma hormones after treatment with 8-OH DPAT. PMID- 7996434 TI - Influence of cell type upon the desensitization of the beta 3-adrenergic receptor. AB - Previous studies have suggested that the beta 3 receptor fails to become desensitized following acute agonist exposure. We have determined whether this resistance to desensitization is an intrinsic property of the human beta 3 receptor by examining beta 3 receptor-stimulated adenylyl cyclase activity in several cell types. Prior exposure to ISO significantly decreased beta 3 receptor stimulated adenylyl cyclase activity in SK-N-MC human neuroepithelioma cells, which natively express the beta 3 receptor. ISO pretreatment significantly desensitized the recombinant beta 3 receptor when stably expressed in 293 cells, but not when the receptor was expressed in Chinese hamster ovary cells. Mutant receptors lacking the second exon of the human beta 3 receptor also underwent agonist-induced desensitization when expressed in 293 cells. Additionally, the rat beta 3 receptor, which fails to desensitize in rat adipocytes, underwent agonist-induced desensitization when expressed in 293 cells. Pretreatment with CGP 12177A, a beta 3-selective agonist, also reduced beta 3-stimulated adenylyl cyclase activity in transfected 293 cells. In contrast, 8-Br-Cyc AMP did not desensitize the beta 3 receptor. Concanavalin A, an inhibitor of receptor sequestration failed to prevent ISO-induced desensitization of the beta 3 receptor. Furthermore, radioligand binding studies showed that ISO pretreatment did not cause a loss of beta 3 receptors from 293 cell membranes. The results of the present study indicate that beta 3 receptor desensitization is dependent upon the cellular background in which this receptor is expressed. Furthermore, the mechanism responsible for beta 3 receptor desensitization does not appear to involve sequestration, cyclic AMP-dependent phosphorylation or down-regulation of the receptor. PMID- 7996435 TI - Alkylglycosides enhance systemic absorption of insulin applied topically to the rat eye. AB - A series of alkylglycosides with various alkyl chain lengths and carbohydrate residues were tested for their ability to enhance systemic absorption of insulin after topical ocular delivery in anesthetized rats. Several reagents, including tetradecyl-, tridecyl- and dodecylmaltoside and dodecylsucrose, were potent stimulators of insulin absorption when used at concentrations as low as 0.125%. Other alkylglycosides such as decylsucrose, decylmaltoside, nonylglucoside, octylmaltoside, heptylglucoside and hexylglucoside were less potent or ineffective as absorption-enhancing reagents. By comparison, the bile salt sodium glycocholate was effective only when used at concentrations of 0.5% or greater. All of the reagents were effective only when used at concentrations above their critical micelle concentration and the most hydrophobic alkylglycoside reagents were the most efficacious at promoting systemic insulin absorption. The possible utilization of eyedrops containing insulin plus an absorption-enhancing alkylglycoside reagent in humans is discussed. PMID- 7996436 TI - Decreased intracellular compartmentalization of doxorubicin in cell lines expressing P-glycoprotein. AB - After initial rapid [14C]doxorubicin distribution into drug-sensitive HL-60 and SU-4 cells, slow uptake continues for more than 4 hr, accounting for up to 80% of the total intracellular drug. In contrast, in P-glycoprotein-expressing drug resistant HL-60R and SU-4R cells, doxorubicin distribution rapidly approaches equilibrium. The simplest kinetic model of this behavior consists of rapid diffusion from extracellular fluid into the cell, followed by uptake into a nonexchangeable intracellular pool. At 3.4 microM doxorubicin, transmembrane diffusion clearance was similar for all cell lines (0.78-0.98 microliter sec-1). There was no decrease in the normalized apparent volume of distribution in the P glycoprotein-expressing cell lines, as would be expected if an active, unidirectional efflux were present. However, in resistant cells, doxorubicin accumulation in the nonexchangeable pool was up to 15-fold slower than in sensitive cells (0.004 vs. 0.050 microliter sec-1 in HL-60R vs. HL-60; 0.004 vs. 0.058 microliter sec-1 in SU-4R vs. SU-4). No pool inflow could be detected in either SU-4 or SU-4R cells exposed to doxorubicin at 0 degrees C, indicating that the nonexchangeable accumulation requires energy. The process preventing accumulation began to saturate in SU-4R cells at 20 microM doxorubicin, whereas no evidence of saturation was seen with HL-60R, which is more highly resistant than SU4R. We propose that alteration in compartmentalization is primarily responsible for the doxorubicin resistance observed in these cell lines. PMID- 7996437 TI - Effects of prenatal ethanol exposure on N-methyl-D-aspartate-mediated calcium entry into dissociated neurons. AB - The effects of prenatal ethanol exposure on N-methyl-D-aspartate (NMDA)-activated calcium entry into dissociated neurons were studied. Dissociated brain cells were isolated from less than 1-day-old pups from prenatally ethanol-exposed, pair-fed control and ad libitum control groups and loaded with fura-2. Prenatal ethanol exposure significantly decreased the NMDA receptor-mediated calcium entry compared to both pair-fed and ad libitum control groups. To determine the mechanisms of the prenatal ethanol exposure on the NMDA-mediated ion channel decrements, possible modulatory sites of the NMDA receptor were studied. Glycine (0.1, 1, 10 and 100 microM) increased calcium entry to an equal extent in the ethanol and control groups, but did not reverse the effect of prenatal ethanol exposure. Furthermore, low concentrations of MK801 [(+)-5-methyl-10,11-dihydro-5H dibenzo[a,d]-cyclohepten-5-10-imine hydrogen maleate] (25 and 50 nM) did not further inhibit calcium entry beyond that observed with the prenatal ethanol exposure, but significantly inhibited control group responses. Mg++ showed a similar result. With increasing concentrations of Mg++ the calcium entry in the three groups tended to converge. Thus, these results suggest that prenatal ethanol exposure inhibits the function of NMDA receptor-mediated ion channels by possibly altering the structural properties of the ion channel itself and/or by interacting with inner ion channel modulatory sites activated by Mg++ or MK801, and not the glycine site. PMID- 7996438 TI - Neonatal hypoxia: early neurotransmitter responses and the consequences of treatment with GM1 ganglioside. AB - Brain neurotransmitter content and uptake activity were assessed in the brains of 7-day-old rats 15 min after exposure to hypoxia (8% O2-92% N2) for 3 hr. Glutamate, dopamine and choline uptake were decreased in the striatum, hippocampus and frontal cortex of the hypoxic animals. Moreover, the content of glutamate, dopamine and serotonin as well as the acidic metabolites of the two biogenic amines increased in the same tissues. Acetylcholine content was decreased in all three brain regions as well. Treating the animals with GM1 ganglioside before the insult prevented all neurochemical changes in the hypoxic neonatal brain. GM1 also prevented an hypoxia-induced decrease in phorbol ester binding. Finally, GM1 ganglioside reduced the mortality rate resulting from the hypoxic insult. Our results along with those in the literature suggest that GM1 might be useful for combating the pathology associated with perinatal hypoxia. PMID- 7996439 TI - Antinociceptive actions of dexmedetomidine and the kappa-opioid agonist U-50,488H against noxious thermal, mechanical and inflammatory stimuli. AB - The antinociceptive efficacies of both intrathecally (i.t.) and systemically administered dexmedetomidine (a selective alpha-2 adrenoceptor agonist) and U 50,488H [trans(+/-)-3,4-dichloro-N-methyl-N-[2-(1-pyrrolidinyl)-cyclohexyl]- benzene-acetamide] (a kappa-opioid receptor agonist) were studied during peripheral inflammation induced by carrageenan. The antinociceptive tests were the hot plate (HP), the tail flick (TF) and the paw pressure tests (PP). The motor incoordination, if any, produced by both i.t. and s.c. dexmedetomidine were evaluated with the rotarod. The interaction between dexmedetomidine and U-50,488H and between atipamezole (a selective alpha-2 adrenoceptor antagonist) and U 50,488H were also assessed. The carrageenan injection induced not only peripheral hyperalgesia but also central sensitization, as assessed by decreased PP and TF latencies, respectively. The i.t. dexmedetomidine (0.15, 0.45, 1.35, 4.05) micrograms) resulted in dose-dependent increases in the PP thresholds and TF latencies in both the control rats and the rats with unilateral inflammation, without causing changes in motor coordination, whereas on s.c. administration of dexmedetomidine (3-100 micrograms/kg), antinociception was produced in PP only at doses (30 micrograms/kg) that already interfered with rotarod performance. U 50,488H was ineffective i.t. (5-200 micrograms) but, on s.c. administration (2.5 22.5 mg/kg), dose-dependent increases were found in the PP thresholds and TF latencies of the rats with unilateral inflammation. Atipamezole, in a dose (3 mg/kg) that has been shown to block the antinociceptive effects of dexmedetomidine, did not modify the antinociceptive effects of U 50,488H.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7996440 TI - Alaproclate acts as a potent, reversible and noncompetitive antagonist of the NMDA receptor coupled ion flow. AB - We studied the effect of alaproclate [2-(4-chlorophenyl)-1,1-dimethyl 2 aminopropanoate] on the N-methyl-D-aspartate (NMDA)-induced changes in membrane potential and intracellular free Ca++ in cerebellar granule cells by using the fluorescent indicators DiBaC4(3) and fura-2, respectively. The NMDA-induced responses were blocked by the 5-hydroxytryptamine reuptake blocker alaproclate in a noncompetitive manner with an IC50 value of 0.3 microM. The effect of alaproclate was stereoselective because the S-(-)-enantiomer was more potent than the R-(+)-enantiomer. The inhibitory response was rapidly reversed if alaproclate was removed by perfusion. The same was the case with the reversible noncompetitive NMDA receptor antagonists dextromethorphan, dextrorphan, amitriptyline and desipramine. The inhibition caused by the noncompetitive antagonist dizolcipine could not be reversed by perfusion. The glycine sensitivity of the NMDA response was unaffected by alaproclate, and high concentrations of glycine were unable to reverse the inhibition of alaproclate. Alaproclate also did not affect the sensitivity of the responses to Mg++. The results suggest that alaproclate, which has previously been in clinical trials for depressive illness, acts as a reversible noncompetitive antagonist of the NMDA receptor. PMID- 7996441 TI - Protection against methamphetamine-induced neurotoxicity to neostriatal dopaminergic neurons by adenosine receptor activation. AB - Methamphetamine (METH)-induced neurotoxicity to nigrostriatal dopaminergic neurons in experimental animals appears to have a glutamatergic component because blockade of N-methyl-D-aspartate receptors prevents the neuropathologic consequences. Because adenosine affords neuroprotection against various forms of glutamate-mediated neuronal damage, the present studies were performed to investigate whether adenosine plays a protective role in METH-induced toxicity. METH-induced decrements in neostriatal dopamine content and tyrosine hydroxylase activity in mice were potentiated by concurrent treatment with caffeine, a nonselective adenosine antagonist that blocks both A1 and A2 adenosine receptors. In contrast, chronic treatment of mice with caffeine through their drinking water for 4 weeks, which increased the number of adenosine A1 receptors in the neostriatum and frontal cortex, followed by drug washout, prevented the neurochemical changes produced by the treatment of mice with METH treatment. In contrast, this treatment did not prevent 1-methyl-4-phenyl-1,2,3,6- tetrahydropyridine-induced dopaminergic neurotoxicity. Furthermore, concurrent administration of cyclopentyladenosine, an adenosine A1 receptor agonist, attenuated the METH-induced neurochemical changes. This protection by cyclopentyladenosine was blocked by cyclopentyltheophylline, an A1 receptor antagonist. These results indicate that activation of A1 receptors can protect against METH-induced neurotoxicity in mice. PMID- 7996442 TI - Transport of cefadroxil in rat kidney brush-border membranes is mediated by two electrogenic H+-coupled systems. AB - The transport characteristics of the aminocephalosporin [3H]cefadroxil have been studied in brush-border membrane vesicles (BBMV) of rat kidney cortex by a rapid filtration technique and by use of a potential sensitive fluorescent dye. Influx of [3H]cefadroxil (0.25 microM) into BBMV as a function of time displayed a pronounced overshoot phenomenon in the presence of a transmembrane pH gradient (pHin > pHout). Evidence for an electrogenic cefadroxil/H+-symport in the presence of an inwardly directed proton gradient is provided by the demonstration of: 1) reduced uptake in the presence of a protonophore; 2) reduced uptake under voltage clamp conditions; and 3) increased uptake in the presence of a valinomycin-induced inside negative K+-diffusion potential. pH-gradient dependent uptake of [3H]cefadroxil as a function of substrate concentration revealed the presence of multiple carrier systems. By kinetic analysis, a high-affinity carrier system (Km, 8.8 +/- 1.3 microM) and a low-affinity system (Km, 2.62 +/- 0.80 mM) could be resolved. The high-affinity transport system was found to be very specific for substrates (cephalosporins and di- and tripeptides) carrying an alpha-amino group. By use of a potential sensitive fluorescent dye 3,3' dipropylthiadicarbocyanine iodide, the low-affinity transport system was characterized with respect to its driving force and its kinetic features. This transporter was found also to be electrogenic in nature, representing a second cefadroxil/H+-symport system. In summary, our studies demonstrate for the first time uphill transport of cefadroxil in kidney BBMV mediated by multiple carrier systems. Transport is rheogenic, energized by the proton motive force and shared by other aminocephalosporins as well as di- and tripeptides.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7996443 TI - Antihypertensive effects of metformin in fructose-fed hyperinsulinemic, hypertensive rats. AB - In the present study, we examined the relationship between elevated insulin levels and hypertension in the fructose-hypertensive rat model, in which the rise in blood pressure is induced by feeding normal rats a fructose-enriched diet. Six week-old Sprague-Dawley rats were divided into four experimental groups: control (C, n = 8), control metformin-treated (CT, n = 8), fructose-fed (F, n = 9) and fructose-fed, metformin-treated (FT, n = 10). Long-term oral metformin treatment (500 mg/kg/day) was begun in the CT and FT groups, and 1 week after the initiation of metformin treatment, the F and FT groups started receiving a 66% fructose diet. Metformin treatment prevented the increase in plasma insulin levels in the FT rats (FT, 32 +/- 4 microU; F, 51 +/- 7 microU-ml; P < .001) without any change in plasma glucose levels. Interestingly, metformin treatment also prevented the increase in systolic blood pressure in the FT group (FT, 143 +/- 2 mm Hg; F, 159 +/- 2 mm Hg; P < .001) but had no effect in the CT group (CT, 142 +/- 3 mm Hg; versus C, 141 +/- 2 mm Hg; P > .05). Restoration of plasma insulin levels in the FT group to levels that existed in the untreated F rats reversed the effect of metformin on blood pressure (FT plus insulin, 158 +/- 3 mm Hg; F, 160 +/- 3 mm Hg; P > .05). In conclusion, metformin prevents the hyperinsulinemia and hypertension that occur after feeding normal rats a fructose enriched diet. Also, the antihypertensive effects of metformin can be reversed by raising the plasma insulin levels in the treated rats to those that exist in the untreated fructose-fed group, which suggests that hyperinsulinemia may contribute toward the increase in blood pressure in this model of experimental hypertension. PMID- 7996444 TI - In the search for a novel class of antipsychotic drugs: preclinical pharmacology of FG5803, a 1-piperazinecarboxamide derivative. AB - Comparative studies of the 1-piperazinecarboxamide derivative 4-[3-(4 fluorobenzoyl)propyl]-N-cyclohexyl-1-piperazinecarboxamide hydrochloride (FG5803) were made with clozapine and haloperidol. Receptor studies revealed that FG5803 potently and selectively bound to the serotonin type 2A receptors (Ki = 13 nM). FG5803 inhibited 5-hydroxytrophan- and 1-(2,5-dimethoxy-4-iodophenyl)-2 aminopropane-induced head twitches, which indicated potent in vivo serotonin type 2A receptor antagonism. FG5803 caused an acute activation of the tuberoinfundibular dopamine neurons and produced only a transient rise in plasma prolactin. In behavioral studies in rats, FG5803 showed strong antagonistic action on presynaptic dopaminergic autoreceptors but only weak postsynaptic dopamine D2 blockade. FG5803 was not cataleptogenic and did not antagonize amphetamine-induced stereotypies. FG5803 was active in the reduction of aggressive behavior and spontaneous exploratory behavior in mice and rats. Therefore, FG5803 is expected to constitute a promising approach in the search for a novel class of antipsychotic drugs that have a broader spectrum of activity and fewer adverse effects than the conventional, antidopaminergic antipsychotics. PMID- 7996445 TI - Effects of a new class of calcium antagonists, SR33557 (fantofarone) and SR33805, on neuronal voltage-activated Ca++ channels. AB - SR33557 (fantofarone) and SR33805 are structurally novel calcium antagonists that bind selectively to the alpha 1-subunit of the L-type Ca++ channel at a site distinct from the classical 1,4-dihydrophyridine, phenylalkylamine and benzothiazepine sites but in allosteric interactions with them. Blocking effects of fantofarone and SR33805 on the different types of voltage-activated Ca++ currents have been investigated with the whole-cell patch-clamp method in chick dorsal root ganglion neurons (for T-, L- and N-type currents) and in rat cerebellar Purkinje neurons (for P-type current) in primary culture. Neuronal L type Ca++ channels are blocked totally by fantofarone and SR33805 in the microM range of concentration as in skeletal muscle and cardiac cells at a holding membrane potential of -80 mV. The sequence of efficacy is SR33805 (IC50 = 26 nM) > fantofarone (IC50 = 0.35 microM). N- and P-type channels are not very sensitive to fanto-farone and SR33805 (IC50 approximately 5 microM). The T-type channel is not affected by these drugs. PMID- 7996446 TI - Enhancement by O6-benzyl-N-acetylguanosine derivatives of chloroethylnitrosourea antitumor action in chloroethylnitrosourea-resistant human malignant melanocytes. AB - The exposure of cells to O6-methylguanine or O6-benzylguanine is known to reduce the enzymatic activity of O6-alkylguanine-DNA alkyltransferase, which leads to a sensitivity enhancement to chloroethylnitrosourea cytotoxic effects. The main disadvantage of the guanine derivatives is their low water solubility, which makes their formulation difficult for clinical use in humans. To overcome this problem, water-soluble O6-alkylguanine-DNA alkyltransferase inhibitors have been synthesized and their ability to increase the chloroethylnitrosourea potency in vitro and in vivo was evaluated. Four water-soluble molecules (O6-methyl-N acetylguanosine; O6-methyl-N-acetyldeoxyguanosine; O6-benzyl-N-acetylguanosine, BNAG; and O6-benzyl-N-acetyldeoxyguanosine, BNADG) were tested for sensitivity of M4Beu cells to N'-(2-chloroethyl]-N[2-(methylsulfonyl)ethyl]-N'-nitrosourea (cystemustine) based on the colony-forming ability of M4Beu melanoma cells. The cell sensitivity to cystemustine was increased by benzylated derivative pretreatment but not with methylated derivative pretreatment. Furthermore, BNAG or BNADG pretreatment followed by cystemustine was less cytotoxic than BNAG or BNADG given simultaneously and followed 24 hr later by BNAG or BNADG. Comparative studies performed with O6-benzylguanine on the same model showed that this inhibitor was effective at lower concentrations than the corresponding guanosine or deoxyguanosine analogs. Preliminary pharmacological assays were carried out in nude mice bearing the M4Beu tumor to determine whether the BNAG-cystemustine combination has greater antitumor activity than cystemustine alone. Simultaneous i.p. injection of 200 mg/kg of BNAG and 15 mg/kg of cystemustine followed by an i.p. injection 4 hr later of 200 mg/kg of BNAG led to a significant enhancement of inhibition of tumor growth. PMID- 7996447 TI - Ca++ mobilization mediated by endothelin ETA receptor in endothelium of rabbit aortic valve. AB - The mechanism of Ca++ mobilization induced by endothelins (ETs) and the receptor subtype responsible for this effect were examined in the endothelium of rabbit aortic valve. In the endothelium loaded with fura-2, ET-1 (1-100 nM) induced large transient increase followed by small sustained increase in cytosolic Ca++ level ([Ca++]i) in a concentration-dependent manner. ET-3 induced only a small increase in [Ca++]i at higher concentrations (100-300 nM) than ET-1, whereas a selective ETB agonist, 100 nM IRL 1620 (succinyl-[Glu9, Ala11,15]ET-1 8-21), was ineffective. A selective ETA antagonist, 3 microM BQ-123, (cyclo [-Asp-Pro-Val Leu-Trp-]) but not a selective ETB antagonist, 10 microM RES-701-1 [cyclic (Gly1 Asp9) (Gly-Asn-Trp-His-Gly-Thr-Ala-Pro-Asp- Trp-Phe-Phe-Asn-Tyr-Tyr-Trp)], inhibited the effects of ET-1 and ET-3. The sustained increase in [Ca++]i induced by ET-1 was abolished by 30 microM La , although 100 nM nicardipine was ineffective. In the absence of external Ca++ (with 0.5 mM EGTA), ET-1 induced only a transient increase in [Ca++]i, which was inhibited by an inhibitor of Ca+(+)-ATPase in endoplasmic reticulum, 1 microM thapsigargin. However, an inhibitor and an activator of Ca+(+)-induced Ca+(+)-release channel, 10 microM ryanodine and 10 mM caffeine, did not change [Ca++]i. These results suggest that, in the endothelium of rabbit aortic valve, only the ETA receptor mediates the effects of ETs to increase [Ca++]i, which is attributable to the release of Ca++ from thapsigargin-sensitive and ryanodine-insensitive Ca++ stores and also to the Ca++ influx through La (-)sensitive and dihydropyridine-insensitive Ca++ channels. PMID- 7996448 TI - Involvement of NMDA receptors in naloxone-induced contractions of the isolated guinea pig ileum after preincubation with morphine. AB - N-Methyl-D-aspartate (NMDA) antagonists attenuate morphine tolerance and dependence. To test the hypothesis that morphine increases NMDA activity, generating conditions necessary for withdrawal, we examined the role of NMDA receptors in the action of morphine in the guinea pig ileum (GPI). Glutamate produced contractions of the GPI with an EC50 of 24.6 microM. Morphine inhibited contractions induced by glutamate (10-500 microM) with a Ke of 10.2 nM. Naloxone, which produced no effect alone, prevented the inhibitory effects of morphine on glutamate-induced contractions (Ke = 19.3 nM) as well as on electrically induced contractions (Ke = 18.0 nM), suggesting that opioid receptors with similar affinities mediate both inhibitory effects of morphine. Exposure to morphine for 10 to 50 min resulted in acute dependence, characterized by contractions induced by 0.1 to 4 microM naloxone. Responses to naloxone were maximal after a 20-min incubation with 50 nM morphine. Increasing the concentration of morphine or the incubation time did not further increase the degree of dependence. Competitive ((+/-)-3-(2-carboxypiperazin-4-yl)-propyl-1-phosphonic acid) and R(-)-2 amino-5 phosphonovaleric acid) and noncompetitive (MK-801) antagonists of NMDA inhibited naloxone-induced contractions. After 20 min of incubation with morphine followed by naloxone challenge, the EC50 for glutamate was decreased by a factor of 3.2, reflecting an enhanced sensitivity to NMDA. These data show that activation of NMDA receptors and enhanced sensitivity to glutamate are important components of naloxone-precipitated contractions of the GPI after incubation with morphine. PMID- 7996449 TI - The cardiac effects of a novel A1-adenosine receptor agonist in guinea pig isolated heart. AB - Adenosine increases atrioventricular (AV) nodal conduction time and is used for termination of AV nodal re-entrant tachycardias, but it is rapidly metabolized. The purposes of the present study were to characterize the cardiac actions and effects of an orally active and stable adenosine analog, N6-cyclohexyl-2-O methyladenosine (SDZ WAG-994) and to evaluate its potential as an antiarrhythmic agent. Guinea pig hearts were isolated and perfused with oxygenated Krebs Henseleit solution. SDZ WAG-994 slowed the atrial rate and prolonged the AV nodal conduction time of spontaneously beating hearts in a concentration-dependent manner. The EC50 values for the negative chronotropic and dromotropic effects of SDZ WAG-994 were 0.69 +/- 0.04 and 1.49 +/- 0.54 microM, respectively. The A1 receptor antagonist 8-cyclopentyl-1,3-dipropylxanthine (0.2 microM) significantly antagonized SDZ WAG-994-induced stimulus-to-His bundle (S-H) interval prolongation. The negative dromotropic effect of SDZ WAG-994 showed very strong frequency dependence. In hearts paced at an atrial cycle length of 300 msec (200 beats/min), the EC50 value of SDZ WAG-994 to prolong the S-H interval was 3.7 fold lower (0.40 +/- 0.02 microM) than in unpaced hearts, and at atrial pacing cycle lengths of 500 and 250 msec, 0.3 microM SDZ WAG-994 prolonged the S-H interval by 8 and 26 msec, respectively. SDZ WAG-994 also decreased coronary perfusion pressure (EC50 = 1.50 +/- 0.80 microM); this effect of SDZ WAG-994 was attenuated by adenosine deaminase and by 8-cyclopentyltheophylline (2 microM). Radioligand binding assays revealed that SDZ WAG-994 had a 280-fold greater affinity for A1- than for A2a receptors of the guinea pig brain. The marked frequency dependence of the negative dromotropic effect of SDZ WAG-994 suggests that this A1 agonist may be highly effective in the termination of AV nodal re entrant tachycardias. PMID- 7996451 TI - Relative sensitivity to naloxone of multiple indices of opiate withdrawal: a quantitative dose-response analysis. AB - In addition to classic somatic signs of opiate withdrawal, a number of behavioral measures are known to be sensitive, reliable indices of naloxone-precipitated opiate withdrawal in rats. It has been suggested that some behavioral indices of withdrawal may be more sensitive to precipitation by naloxone than some somatic signs of withdrawal. The purpose of the present study was to permit a quantitative assessment of the relative sensitivity to naloxone of a variety of behavioral and somatic indices of opiate withdrawal. Male Wistar rats were implanted s.c. with either two morphine (each 75 mg of base) or two placebo pellets. No sooner than 3 days after implantation, naloxone dose-response functions were determined with several behavioral paradigms and ratings of a variety of somatic withdrawal signs. In dependent rats, very low (0.004 or 0.01 mg/kg) doses of naloxone produced the following behavioral effects: 1) a reduction in spontaneous locomotor activity, 2) a disruption of schedule controlled (fixed ratio 15) operant responding for food, 3) an elevation in intracranial self-stimulation thresholds and 4) a conditioned place aversion. These same doses of naloxone produced no significant effects in nondependent (placebo pellet-implanted) rats. The ED50 values for naloxone precipitation of all behavioral signs of withdrawal were below 0.013 mg/kg; the ED50 values for naloxone precipitation of most somatic withdrawal signs were higher. The behavioral measures used in these studies therefore represent highly sensitive indices of opiate withdrawal. PMID- 7996450 TI - Development of cross-tolerance between delta 9-tetrahydrocannabinol, CP 55,940 and WIN 55,212. AB - In previous studies it was shown that the structurally dissimilar compounds delta 9-THC, CP 55,940 and WIN 55,212 produced more or less the same pharmacological effects and interacted with the same cannabinoid receptor. However, their potencies vary across a number of pharmacological assays, suggesting that a single mechanism may not account for all of their actions. To further explore possible differences among these cannabinoids, cross-tolerance studies were conducted. Specifically, the ability of delta 9-THC, CP 55,940 and WIN 55,212 to produce hypoactivity, hypothermia, antinociception and catalepsy was assessed in mice that had been chronically treated with either delta 9-THC or CP 55,940. The results indicated the delta 9-THC-treated mice were tolerant to delta 9-THC. The degrees of tolerance were 15.9, 7.8, and 13.4 for spontaneous activity, hypothermia and antinociception, respectively. Mice chronically treated with delta 9-THC also exhibited tolerance to some of the behavioral effects of CP 55,940 and WIN 55,212. The tolerance induced by repetitive administration of CP 55,940 was substantial. The ED50 for CP 55,940 was shifted 102 fold for spontaneous activity, 100 for hypothermia and 44 for catalepsy. Also, some cross tolerance to delta 9-THC and WIN 55,212 was observed in CP 55,940 chronically treated mice. These findings indicate that cross-tolerance develops between delta 9-THC, CP 55,940 and WIN 55,212 and that these agents have some actions in common. However, quantitative differences in their development of cross-tolerance suggests that all of their actions may not be identical. PMID- 7996452 TI - Tepoxalin: a dual cyclooxygenase/5-lipoxygenase inhibitor of arachidonic acid metabolism with potent anti-inflammatory activity and a favorable gastrointestinal profile. AB - Tepoxalin [5-(4-chlorophenyl)-N-hydroxy-(4-methoxyphenyl)-N-methyl-1H- pyrazole-3 propanamide] is a potent inhibitor of sheep seminal vesicle cyclooxygenase (CO) (IC50 = 4.6 microM), rat basophilic leukemia cell (RBL-1) lysate CO (IC50 = 2.85 microM) and CO from intact RBL-1 cells (IC50 = 4.2 microM). The compound inhibits the production of thromboxane B2 (TxB2) in Ca++ ionophore A-23187-stimulated human peripheral blood leukocytes (HPBL; IC50 = 0.01 microM) and human whole blood (IC50 = 0.08 microM) and is a potent inhibitor of epinephrine-induced human platelet aggregation (IC50 = 0.045 microM). Tepoxalin inhibits lipoxygenase (LO) in RBL-1 lysates (IC50 = 0.15 microM) and intact RBL-1 cells (IC50 = 1.7 microM) and inhibits the generation of leukotriene B4 (LTB4) in calcium ionophore A-23187 stimulated HPBL (IC50 = 0.07 microM) and human whole blood (IC50 = 1.57 microM). Human platelet 12-LO (IC50 = 3.0 microM) is inhibited, but 15-LO is only weakly so (IC50 = 157 microM). In vivo, tepoxalin, administered orally, demonstrated potent anti-inflammatory activity in the established adjuvant arthritic rat (ED50 = 3.5 mg/kg) and potent analgesic activity in the acetic acid abdominal construction assay in mice (ED50 = 0.45 mg/kg). In an ex vivo whole blood eicosanoid production assay, tepoxalin produces a dose-related inhibition of prostaglandin (PG) and LT production in dogs (PGF2 alpha - ED50 = 0.015 mg/kg; LTB4 - ED50 = 2.37 mg/kg) and adjuvant arthritic rats following oral administration. In adjuvant arthritic rats, tepoxalin is devoid of ulcerogenic activity within its anti-inflammatory therapeutic range (1-33 mg/kg p.o.) and does not exhibit ulcerogenic activity in normal rats at doses lower than 100 mg/kg (UD50 = 173 mg/kg p.o.). Tepoxalin represents a new class of anti inflammatory drugs which may exhibit less gastrointestinal toxicity and may be efficacious in immunoinflammatory disease states where excessive PG and LT production has been implicated and may offer a significant alternative to nonsteroidal and corticosteroidal anti-inflammatory therapy. PMID- 7996453 TI - Effects of felodipine on left ventricular systolic and diastolic performance in congestive heart failure. AB - We studied the effects of a dihydropyridine calcium blocker, felodipine, on left ventricular (LV) contractile performance and diastolic filling dynamics in conscious dogs with pacing-induced congestive heart failure (CHF) before and after autonomic blockade. Eleven conscious dogs were instrumented to measure micromanometer LV and left atrial (LA) pressure (P) and to determine LV volume (V) from three dimensions. CHF was induced by 4 to 5 weeks of right ventricular pacing. After CHF, the mean LV end-diastolic (ED) P increased (9.7 +/- 2.9 vs. 27.9 +/- 6.8 mm Hg, P < .05), LVEDV and end-systolic (ES) V increased and stroke volume (SV) decreased (15.3 +/- 2.4 vs. 9.6 +/- 3.0 ml, P < .05). The time constant of LV relaxation (T) (25.9 +/- 2.9 vs. 37.9 +/- 5.1 msec, P < .05) and LVES wall stress (WS) (63.4 +/- 21.0 vs. 74.6 +/- 23.7 g/cm2, P < .05) also increased. After CHF, felodipine (25 nmol/kg i.v., plasma concentrations 17.4 +/- 3.2 nmol/L) produced significant decreases in LVESP (119 +/- 12 vs. 96 +/- 11 mm Hg, P < .05), arterial elastance, total systolic resistance (TSR) (0.11 +/- 0.04 vs. 0.07 +/- 0.03 mm Hg/ml/min, P < .05) and LVESWS (74.6 +/- 23.7 vs. 60.2 +/- 17.3 g/cm2, P < .05). Felodipine increased the slopes of the ESP-V relation (5.6 +/- 1.5 vs. 7.8 +/- 0.7 mm Hg/ml, P < .05), the dP/dtmax-EDV relation (51.4 +/- 6.1 vs. 85.3 +/- 10.1 mm Hg/ml sec, P < .05) and the stroke work-EDV relation (69.8 +/- 7.1 vs. 78.9 +/- 7.1 mm Hg, P < .05) and shifted all three relations to the left, indicating enhanced contractile performance.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7996454 TI - BIRM 270: a novel inhibitor of arachidonate release that blocks leukotriene B4 and platelet-activating factor biosynthesis in human neutrophils. AB - (S)-N-[2-Cyclohexyl-1-(2-pyridinyl)ethyl]-5-methyl-2-benzoxazolamine+ ++ (BIRM 270) was identified as a potent and enantiomerically selective inhibitor of calcium ionophore A23187-stimulated leukotriene B4 biosynthesis in human neutrophils. The (S)- and (R)-enantiomers exhibited IC50 values of 1 nM and 40 nM, respectively. BIRM 270 did not inhibit 5-lipoxygenase activity in a cell-free assay. In addition, the compound did not interfere with the conversion of exogenous 5-lipoxygenase substrate (15S)-hydroperoxyeicosatetraenoic acid to (5S, 15S)-dihydroxyeicosatetraenoic acid in intact, ionophore-stimulated neutrophils. Under the same experimental conditions, BIRM 270 inhibited the production of 5 lipoxygenase products from endogenous substrate, suggesting that the compound affected arachidonate availability rather than metabolism. Consistent with this concept, the inhibition of leukotriene B4 biosynthesis by BIRM 270 was overcome by the addition of exogenous arachidonic acid to the leukocyte preparation. Direct measurement of free arachidonate by gas chromatography-mass spectrometry confirmed that BIRM 270 inhibited arachidonate release from ionophore-stimulated neutrophils. The compound did not affect arachidonate reacylation. The blockage of arachidonate release coincided with inhibition of leukotriene B4 biosynthesis in these cells. BIRM 270 also inhibited ionophore-stimulated platelet-activating factor biosynthesis by human neutrophils. Although these results suggest that BIRM 270 inhibited phospholipase A2-mediated deacylation of membrane phospholipids, the compound did not directly inhibit the high molecular weight, cytosolic phospholipase A2 derived from human neutrophils or U937 cells. Thus, suppression of arachidonate mobilization by BIRM 270 may be due to indirect inhibition of intracellular phospholipase A2 or to inhibition of another acylhydrolase activity. PMID- 7996455 TI - Regio- and stereoselective epoxidation of arachidonic acid by human cytochromes P450 2C8 and 2C9. AB - In the present study, the regio- and stereoselective epoxidation of arachidonic acid by cytochromes P450 2C8 and 2C9, two members of the CYP2C gene subfamily expressed in human liver, was determined. Purified P450 isozymes, reconstituted with NADPH:P450 oxidoreductase, cytochrome b5 and lipid, or microsomes isolated from human liver, were incubated with [1-14C]-arachidonic acid. For regioselective analysis, the epoxide metabolites formed, 14,15-, 11,12- and 8,9 epoxyeicosatrienoic acids (EETs), were resolved by reverse-phase high-performance liquid chromatography. P450 2C8 produces only the 14,15- and 11,12-EETs in a 1.25:1.00 ratio. The two epoxides represent 68% of the total metabolites. P450 2C9 produces 14,15-, 11,12- and 8,9-EETs in a 2.3:1.0:0.5 ratio. The three epoxides represent 69% of the total metabolites. Neither P450 isoform catalyzes the formation of 5,6-EET. For chiral analysis, the two major epoxide metabolites, 14,15- and 11,12-EETs, were derivatized to methyl and pentafluorbenzyl esters, respectively. Enantiomers of 14,15- and 11,12-EET esters were subsequently resolved on Chiralcel OB and OD columns (J.T. Baker, Phillipsburg, PA), respectively. Both P450 2C8 and 2C9 are stereoselective at the 14,15- position, preferentially producing 14(R), 15(S)-EET with 86.2% and 62.5% selectivity, respectively. Both enzymes are also stereoselective at the 11,12-position but have the opposite selectivity. P450 2C8 is 81.1% selective for 11(R), 12(S)-EET; P450 2C9 is 69.4% selective for the 11(S), 12(R)-EET. Immunoinhibition studies performed with anti-2C9 immunoglobulin G (which also reacts with P450 2C8) and hepatic microsomes indicate that these two P450s are important arachidonic acid epoxygenases in human liver. PMID- 7996456 TI - Electrophysiological effects of SKF 38393 in rats with reserpine treatment and 6 hydroxydopamine-induced nigrostriatal lesions reveal two types of plasticity in D1 dopamine receptor modulation of basal ganglia output. AB - To examine the role of D1 dopamine receptors in modulating basal ganglia output and how this role may be altered by changes in dopaminergic transmission, the effects of a D1 dopamine agonist on firing rates of substantia nigra pars reticulata (SNpr) neurons were determined in reserpine-treated rats and compared with effects observed in nigrostriatal-lesioned and normal rats. It was confirmed that systemic administration of the D1 dopamine agonist SKF 38393 (10 mg/kg i.v.) induces a small (averaging 20% above base line) increase in firing rates of SNpr neurons in normal rats and significantly inhibits SNpr single unit activity in rats studied 6 to 26 weeks after 6-hydroxydopamine (6-OHDA)-induced substantia nigra dopamine cell lesion. In contrast to results obtained after 6-OHDA lesions, SKF 38393 administration consistently and significantly increased the firing rates of SNpr neurons in rats treated for 6 days with reserpine (1 mg/kg/day s.c.); increases averaged 88% above base line. Five days after the 6-day reserpine treatment was discontinued, administration of SKF 38393 still induced a pronounced increase in SNpr activity. These increases were reversed by the administration of the D1 dopamine antagonist SCH 23390. SKF 38393 also significantly increased the firing rates of a subpopulation of SNpr neurons in rats treated with only a single dose of reserpine (10 mg/kg s.c. 4-7 hr). The difference between responses in reserpine and 6-OHDA-treated rats was not due to the shorter time course of the reserpine treatments, as SKF 38393 did not consistently affect the activity of SNpr neurons 7 days after 6-OHDA nigral dopamine cell lesion. When the subchronic reserpine treatment was administered to rats lesioned previously with 6-OHDA, D1 dopamine agonist-mediated inhibition of SNpr neuronal activity was obtained. The results show that SNpr responses to D1 dopamine agonist administration after reserpine treatment are enhanced ("supersensitive") relative to normal, whereas SNpr responses to D1 dopamine agonists in animals with 6-OHDA-induced dopamine cell degeneration are opposite to those observed in normal and in reserpinized animals. Current models of basal ganglia function predict that D1 dopamine agonists should reduce activity in the SNpr, because D1 dopamine receptors on striatonigral neurons are thought to stimulate striatonigral firing rates and to enhance the release of tau aminobutyric acid in the SNpr. The present results call for modification of these concepts. PMID- 7996457 TI - Structure-activity relationships for cocaine congeners in inhibiting dopamine uptake into rat brain synaptic vesicles and bovine chromaffin granule ghosts. AB - Structure-activity relationships of cocaine congeners were determined in inhibiting reserpine-sensitive, Mg++/ATP-dependent uptake of [3H]dopamine into rat brain synaptic vesicles under initial velocity conditions. The C2 carbomethoxy group could be deleted without loss of activity, whereas movement of this group from axial to equatorial orientation increased the potency. There was no need for the ester linkage between the tropane and phenyl rings, nor was there need for the ethylene bridge between C1 and C5 that makes cocaine a tropane instead of a piperidine structure. The structure-activity relationships were different from those for inhibiting neuronal amine transport or blocking voltage dependent sodium channels. There was no correlation between block of uptake and degree of lipophilicity. The equally lipophilic compounds cocaine and pseudococaine, and WIN 35,065-3 and WIN 35,140, differed in uptake-blocking potency by an order of magnitude (137 vs. 22 microM and 65 vs. 4 microM, respectively). In bovine chromaffin granules, used as a less complex model system for the vesicular uptake system, the rank order of d-amphetamine, cocaine and pseudococaine in perturbing the proton gradient and in changing the membrane potential was different from that in inhibiting uptake. The inhibition of uptake is discussed in terms of the compounds acting as weak bases, transporter substrates or transporter blockers. PMID- 7996458 TI - Potentiation of 5-HT1A receptor-mediated neuroendocrine responses in male but not female rat progeny after prenatal cocaine: evidence for gender differences. AB - The present study investigated the consequences of prenatal cocaine exposure on central serotonin (5-HT) 5-HT1A receptor-mediated function in prepubescent male and female progeny. Pregnant rats received saline or cocaine (15 mg/kg s.c.) twice daily from gestational day 13 through 20. All litters were fostered to nontreated lactating dams. Cocaine did not alter weight gain during pregnancy and did not affect progeny weight at birth or at postnatal day 28. Male and female progeny were tested at a prepubescent age (postnatal day 28) by measuring 1) the stimulation of adrenocorticotropic hormone, corticosterone and renin by a maximally effective dose (0.5 mg/kg s.c.) of the 5-HT1A agonist 8-hydroxy-2-(di-n propylamino) tetralin (8-OH-DPAT); and 2) [3H]8-OH-DPAT-labeled 5-HT1A receptors and [3H]paroxetine-labeled 5-HT uptake sites in hypothalamus, cortex and midbrain. Basal hormone levels were unaffected by prenatal cocaine exposure. However, prenatal cocaine exposure significantly potentiated the adrenocorticotropic hormone (+28%) and renin (+53%) responses to 8-OH-DPAT in male but not female progeny. In contrast, the corticosterone response to 8-OH DPAT was not significantly altered in either male or female progeny. Likewise, the number of 5-HT1A receptors and 5-HT uptake sites in the cortex, midbrain and hypothalamus were unaffected by prenatal cocaine exposure. These data demonstrate that prenatal cocaine exposure can potentiate brain 5-HT1A receptor-mediated function in progeny and that alterations in hypothalamic 5-HT1A function are gender specific. These data suggest the possibility that prenatal cocaine may increase 5-HT1A receptor function in extrahypothalamic brain regions. PMID- 7996460 TI - Inhibition of motilin-induced phase III contractions by pentagastrin in Heidenhain pouch dogs. AB - We compared the inhibitory effects of histamine and pentagastrin (PG) on motilin induced upper gastrointestinal phase III activity in conscious dogs that had surgically prepared Heidenhain pouchs (HP). Contractile activity was measured by means of chronically implanted force transducers, and changes in pH of the perfusate through the HP were monitored simultaneously. Intravenous infusion of PG (4 micrograms/kg-hr) inhibited motilin-induced phase III activity both in the main stomach and in the HP, whereas histamine (40 micrograms/kg-hr) inhibited activity only in the main stomach. Famotidine (0.3 mg/kg, i.v., the dose that completely inhibited gastric acid secretion by PG or histamine) blocked the inhibition of phase III activity induced by histamine but did not affect PG induced inhibition. L-364,718 (1 mg/kg, i.v.), which had no effect on the PG induced decrease in the pH of the perfusate lowered by PG, reversed the inhibition of phase III activity by PG in the HP but not in the main stomach. However, L-364,718, when combined with famotidine, potently reversed the PG induced inhibition of phase III activity both in the main stomach and in the HP. These results show that the inhibitory effect of PG on motilin-induced phase III activity is brought about by two distinctive mechanisms, gastric acid and the cholecystokinin receptors-dependent mechanism, whereas the histamine-induced inhibition is mediated only by gastric acid. In the vagally denervated HP, however, gastric acid is not involved in an inhibitory effect of PG. PMID- 7996459 TI - Oligodeoxynucleotide antisense to the D1 dopamine receptor mRNA inhibits D1 dopamine receptor-mediated behaviors in normal mice and in mice lesioned with 6 hydroxydopamine. AB - The effects of intracerebroventricular (i.c.v.) administration of a 20-mer phosphorothioate oligodeoxynucleotide antisense to the D1 dopamine receptor mRNA (D1 antisense) on D1 dopamine receptor-mediated behaviors were studied in normal mice and in mice with unilateral 6-hydroxydopamine-induced lesions of corpus striatum. Treating mice with D1 antisense inhibited grooming behavior induced by the D1 dopamine receptor agonist SKF 38393 [1-phenyl-2,3,4,5-tetrahydro-1H-3 benzazepine-7,8-diol hydrochloride], the reduction in grooming being related to the amount and length of time D1 antisense was given, with significant reductions in grooming behavior observed within 2 days of repeated injections of D1 antisense. Administering D1 antisense also inhibited rotational behavior induced by SKF 38393 in mice with unilateral 6-hydroxydopamine-induced lesions of corpus striatum. This inhibitory effect on rotational behavior could not be overcome by increasing the dose of SKF 38393. Recovery from inhibition of both grooming and rotational behaviors occurred after cessation of D1 antisense treatment. An oligomer with a similar composition of bases but placed in a random sequence failed to alter grooming or rotational behaviors induced by SKF 38393. In contrast to its effects on D1-mediated behaviors, treatment with D1 antisense had no significant inhibitory effect on stereotyped behavior induced by the D2 dopamine receptor agonist quinpirole [trans-(-)-4,4a,5,6,7,8,8a,9-octahydro-5 propyl-1H(or 2H)-pyrazolo- (3,4g)-quinoline dihydrochloride] in normal mice and produced no significant inhibition of rotational behavior induced either by quinpirole or by the muscarinic cholinergic agonist oxotremorine in 6 hydroxydopamine-lesioned mice.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7996461 TI - The Ca(++)-channel blocker Ro 40-5967 blocks differently T-type and L-type Ca++ channels. AB - The effects of Ro 40-5967, a nondihydropyridine Ca++ channel blocker, on low voltage activated (T-type) and high-voltage activated (L-type) Ca++ channels were compared. L-type barium currents were measured in Chinese hamster ovary cells stably transfected with the alpha 1 subunit of the class Cb Ca++ channel. T-type barium currents were investigated in human medullary thyroid carcinoma cells. The Ba++ currents of human medullary thyroid carcinoma cells were transient, activated at a threshold potential of -50 mV with the maximum at -14 +/- 3.2 mV and blocked by micromolar Ni++. The T- and L-type current inactivated with time constants of 33.4 +/- 4.1 and 416 +/- 26 msec at maximum barium currents, respectively. Ro 40-5967 inhibited reversibly the T- and L-type currents with IC50 values of 2.7 and 18.6 microM, respectively. The inhibition of the L-type current was voltage-dependent, whereas that of the T-type current was not. Ro 40 5967 blocked T-type current already at a holding potential of -100 mV. The different types of block, i.e., voltage-dependent vs. tonic block, may contribute to the pharmacological profile of Ro 40-5967 in intact animals. PMID- 7996462 TI - MEN 10,627, a novel polycyclic peptide antagonist of tachykinin NK2 receptors. AB - We describe the in vitro and in vivo pharmacological properties of MEN 10,627 or cyclo(Met-Asp-Trp-Phe-Dap-Leu)cyclo(2 beta-5 beta), the first example of a polycyclic peptide tachykinin NK2 receptor antagonist. MEN 10,627 is endowed with high affinity for NK2 receptor expressed in various species with pKB values ranging between 10.1 (hamster trachea) and 8.1 (rabbit pulmonary artery). The antagonism is of competitive type in both functional and radioligand binding assays. A 100- to 10,000-fold selectivity was found vs. NK1 or NK3 receptors expressed in various species. As an NK2 receptor antagonist, MEN 10,627 is 10- to 100-fold more potent than the monocyclic peptide antagonist L 659,877 or cyclo(Met-Gln-Trp-Phe-Gly-Leu). At the hamster NK2 receptor, MEN 10,627 is about 30-fold more potent than the nonpeptide NK2 receptor antagonist SR 48,968 [(S)-N methyl-N[4-acetylamino-4-phenylpiperidino)-2-(3,4-dichlorophenyl) butyl]benzamide], whereas the converse is true for the rabbit NK2 receptor. Furthermore, MEN 10,627 is, up to micromolar concentrations, devoid of antagonist properties toward a wide range of transmitters of both peptide and nonpeptide nature. In urethane-anesthetized rats in vivo, MEN 10,627 (10-100 nmol/kg i.v.) produced long-lasting inhibition of contraction of the urinary bladder and duodenum produced by i.v. administration of the NK2 receptor agonist [beta Ala8]NKA(4-10), without affecting the responses produced by i.v. administration of the NK1 receptor agonist [Sar9]SP sulfone or acetylcholine. In anesthetized rats, both MEN 10,627 and SR 48,968 blocked urinary bladder contraction induced by the NK2 receptor agonist after intravenous, intranasal or intraduodenal administration. Equieffective doses of MEN 10,627 producing about 50% inhibition of the response to [beta Ala8]NKA(4-10) in the rat urinary bladder in vivo, were 0.01, 0.03 and 3 mumol/kg after intravenous, intranasal and intraduodenal administration, respectively. The corresponding doses of SR 48,968 were 0.03, 0.1 and 1 mumol/kg, after intravenous, intranasal and intraduodenal administration, respectively. In conclusion, MEN 10,627 is a potent and selective NK2 receptor antagonist, endowed with high potency and long duration of action in vivo, which is not restricted to parenteral administration.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 7996464 TI - Enhanced permeability of tetragastrin across the rat intestinal membrane and its reduced degradation by acylation with various fatty acids. AB - Three types of chemically modified tetragastrin (TG) with fatty acids such as acetyl-TG, caproyl-TG and lauroyl-TG were synthesized and their in vitro intestinal permeability characteristics were estimated by a modified Ussing chamber system using the isolated intestinal membrane of rats. The penetration of TG across the large intestine was increased by conjugation with acetic acid and caproic acid but not lauric acid. Lauroyl-TG, a highly lipophilic derivative, exhibited low permeability across the intestinal membrane. A "bell-shaped" profile was observed between the apparent permeability coefficients and lipophilicity of the acyl-TG derivatives. The stability of acyl-TG derivatives was examined in homogenates of the jejunum, proximal and distal large intestine, liver and plasma. The half-lives for the proteolysis of the TGs were significantly prolonged by chemical modification with fatty acids in each homogenate. Thus, the chemical modification of TG with some fatty acids not only increases the lipophilicity of TG but also reduces its degradation, which resulted in increased intestinal absorption. The extent of the conjugates' hepatic first-pass metabolism was evaluated by gastric acid secretion activities after i.v. and intraportal administration. The amount of gastric acid secretion after intraportal administration of TG was significantly reduced in comparison with that after i.v. administration. On the other hand, conjugation with caproic acid slightly suppressed TG's hepatic first-pass metabolism, which suggests that chemically modified TGs with fatty acids would be more stable than the native TG in the systemic circulation after intestinal absorption. PMID- 7996463 TI - Antinociceptive and response rate-altering effects of kappa opioid agonists, spiradoline, enadoline and U69,593, alone and in combination with opioid antagonists in squirrel monkeys. AB - Effects of the kappa opioid agonists, spiradoline (U62,066), enadoline (CI-977) and U69,593, were examined alone and in combination with the opioid antagonists quadazocine and beta-funaltrexamine in squirrel monkeys that responded under a schedule of shock titration. When given alone, each of these agonists increased the intensity at which the monkeys maintained shock 50% of the time (median shock level, MSL). Lower doses of spiradoline, enadoline and U69,593 increased response rates in some monkeys and higher doses decreased response rates in all monkeys. When given in combination with the opioid antagonist quadazocine, the dose-effect curves of each agonist, both for MSL and response rates, were shifted to the right in a dose-related and parallel manner. The slopes for the regression lines of the Schild plots for each agonist-quadazocine interaction approximated unity and apparent pA2 values for quadazocine in combination with these agonists ranged between 6.68 and 6.81 for MSL and between 6.63 and 6.87 for response rate. The effects of these agonists were not changed by an 8.0 mg/kg dose of beta funaltrexamine that markedly antagonized the effects of morphine. These results parallel those previously obtained with other kappa agonists, such as bremazocine and U50,488 and suggest that the antinociceptive effects of spiradoline, enadoline and U69,593 in the shock-titration procedure in squirrel monkeys relate to activity at non-mu, probably kappa, opioid receptors. PMID- 7996465 TI - Stereochemical analysis and biological activity of 3-hydroxy-leukotriene B4: a metabolite from ethanol-treated rat hepatocytes. AB - Leukotriene B4 (LTB4), a biologically active metabolite derived from arachidonic acid by the 5-lipoxygenase cascade, is inactivated by cytochrome P-450-dependent omega-hydroxylation followed by second oxidation into a omega-carboxyl group. In many tissues, this second step is mediated by alcohol dehydrogenase. Isolated rat hepatocytes metabolized LTB4 in the presence of ethanol and ethoxyresorufin into substantial quantities of 3-hydroxy-LTB4 as determined by mass spectrometry. The absolute configuration of this metabolite was found to be greater than 98% 3(S) hydroxy-LTB4 by comparison to synthetic standards. Investigation of the pharmacologic properties of the 3(S)- and 3(R)-hydroxy-LTB4 revealed that both caused a significant increase in intracellular free calcium in human neutrophils at 1 microM. Both enantiomers also induced thromboxane A2 release from the isolated guinea pig lung in a dose-dependent manner. This activity was fully blocked by a specific LTB4 receptor antagonist, LY223982, with an IC50 of 0.21 microM for LTB4. These results suggested that activation of the LTB4 receptor does not involve significant recognition of the carbon atoms close to the carboxyl moiety of LTB4. The failure of the hepatocyte to metabolically inactivate LTB4 in the presence of ethanol may be of importance to humans, particularly because the bioactive metabolite 3(S)-hydroxy-LTB4 was further metabolized by human neutrophils significantly more slowly than LTB4. PMID- 7996466 TI - Precoupling of alpha-2B adrenergic receptors and G-proteins in transfected PC-12 cell membranes: influence of pertussis toxin and a lysine-directed cross-linker. AB - The ability of pertussis toxin (PTX) pretreatment to alter the binding of [3H]rauwolscine (RAU) to alpha-2B adrenergic receptors expressed in PC12 cells was examined. PTX caused a 30% increase in the Bmax for [3H]RAU and reduced its KD, whereas in the added presence of Na+ and Gpp(NH)p binding was increased to 75% above the level in untreated membranes. Because all three agents act to reduce receptor/G-protein affinity, the increased binding may reflect extensive precoupling of the alpha-2B receptor. The affinity of the agonist epinephrine in displacing [3H]RAU was normally reduced by both Na+ and Gpp(NH)p; however, in PTX treated membranes the effect of Gpp(NH)p was eliminated, and Na+ remained effective. The lysine-directed cross-linking reagent ethyleneglycol bis(succinimidyl)succinate (EGS) was utilized in an attempt to cross-link precoupled receptor and G-protein. Maximal [3H]RAU binding was reduced by EGS in a time- and dose-dependent manner, and this action was reversed by prior incubation with Na+ and Gpp(NH)p, suggesting that EGS did indeed cross-link receptor and G-protein. RAU and epinephrine each provided protection against the effect of EGS. The inclusion of Na+ and Gpp(NH)p during [3H]RAU binding studies was able to restore maximal binding in EGS-treated membranes to the same level as untreated membranes. These results indicate that in the absence of Na+ and Gpp(NH)p at least 40% of the total alpha-2B adrenergic receptors in these membranes exist as a precoupled receptor/G-protein complex which fails to bind [3H]RAU. PMID- 7996468 TI - Effects of fluoroquinolones on cultured articular chondrocytes flow cytometric analysis of free radical production. AB - Using flow cytometry, we previously established in an ex vivo model that fluoroquinolones induce a stimulation of the oxidative metabolism in immature chondrocytes. To assess these findings in an in vitro model, primary cultures of immature articular chondrocytes were incubated with four quinolone solutions: ofloxacin, ciprofloxacin, nalidixic acid at 10 micrograms/ml for 24 hr and pefloxacin at 1, 10 and 100 micrograms/ml for various periods of time (2, 4, 6, 12, 24 and 48 hr). Three fluorochromes were used: DCFH-DA, reflecting cellular production of H2O2, rhodamine 123 (Rh123) and 10-N-nonyl-acridine orange (NAO), which are specific for mitochondrial activity and mass, respectively. In immature chondrocyte cultures treated with pefloxacin, ofloxacin and nalidixic acid at 10 micrograms/ml for 24 hr, levels of cellular fluorescent dichlorofluorescein DCF (oxidized form of DCFH-DA) were significantly higher than in control cells. No significant increase could be registered with ciprofloxacin. In the same experimental conditions, incorporation of Rh123 and NAO was not significantly modified. Pefloxacin (10 micrograms/ml, 24 hr) did not induce any significant increase of DCFH-DA processing either in mature chondrocytes or in alveolar macrophages removed from immature rabbits. Quinolones induce in vitro an early stimulation of the oxidative metabolism in immature but not in mature chondrocytes, a phenomenon that could explain juvenile onset of quinolone arthropathy. This in vitro model could be proposed as an easy and reproducible method for screening potential arthrotoxicity of antimicrobial agents, capable of stimulating the formation of H2O2. PMID- 7996467 TI - The influence of pharmacogenetics on opioid analgesia: studies with codeine and oxycodone in the Sprague-Dawley/Dark Agouti rat model. AB - In the Sprague-Dawley (SD) rat, the O-demethylation of codeine to morphine is catalyzed by cytochrome P4502D1 (CYP2D1), which is absent in the female Dark Agouti (DA) rat. Oxycodone is similar in structure to codeine but, in contrast, has an analgesic potency in humans similar to morphine. The aim of the study was to test whether the DA rat and the SD rat pretreated with the CYP2D1 inhibitor quinine showed attenuation in analgesia to codeine and oxycodone. With the use of the tail flick model, dose-response curves were constructed to codeine, morphine, oxycodone and oxymorphone (the O-demethylated metabolite of oxycodone) in both rat strains. Codeine did not induce analgesia in the DA rat and there was a 60% reduction in codeine analgesia in the SD rat pretreated with quinine in comparison to the untreated SD rat. In the DA rat, the ED50 to oxycodone was increased 10-fold but there was a significant (P = .0001) prolongation in the duration of analgesia in comparison to that in the untreated SD rat. In the quinine-pretreated SD rat, there was no reduction in oxycodone analgesia but the duration of analgesia was also prolonged. It was concluded that 1) codeine mediated analgesia requires the formation of morphine through the functional activity of CYP2D1 and 2) oxycodone-mediated analgesia may only be partly dependent on CYP2D1. PMID- 7996469 TI - Stimulatory pathways and sites of action of intrathecally administered nicotinic agents. AB - Intrathecal (i.t.) administration of nicotinic agonists to rats elicits a receptor-mediated pressor response, a heart rate increase and irritation nociceptive behavior. We examined the stimulatory pathways and sites of action of spinally administered nicotinic agonists. The thoracic region appears more sensitive to nicotine-elicited pressor actions than the lumbar or cervical regions of the spinal cord. Nicotinic receptors evoking a nociceptive response appear to be located over an area extending from the lumbar rostrally to the thoracic region. Similar to the pressor response, the thoracic spinal cord is the most sensitive region to nicotine in producing the heart rate increase. The cervical region is the least responsive to nicotine, suggesting sites of actions caudal to the brain stem. Intravenous infusion of trimethaphan inhibited the nicotine-elicited pressor response and tachycardia without affecting the irritation response. This suggests that the cardiovascular responses to spinal nicotinic agonists result from enhanced sympathetic outflow. Intrathecal morphine and MK-801 block spinal nicotine-elicited irritation and tachycardia but not the pressor response, indicating that pressor and irritation responses involve independent receptor-mediated pathways. Tachycardia may be associated with the irritation response. In contrast to nicotine, both pressor and irritation responses to cytisine were blocked by morphine with no effect on heart rate. Spinal transection at the T1-2 level eliminated the nociceptive response to nicotine but not the pressor response. Cytisine responses were similar to nicotine; however, cytisine was significantly less potent as a pressor agent in the transected compared with intact animals.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7996470 TI - The novel alpha-2 adrenergic radioligand [3H]-MK912 is alpha-2C selective among human alpha-2A, alpha-2B and alpha-2C adrenoceptors. AB - We have determined the binding affinities of the novel alpha-2 adrenoceptor antagonist radioligand [3H]-MK912 for the cloned human alpha-2A, alpha-2B and alpha-2C adrenoceptors. The KD-values were 1.25 nM, 1.36 nM and 0.086 nM for the alpha-2A, alpha-2B and alpha-2C subtypes, respectively. Thus, the selectivity of [3H]-MK912 for the human alpha-2C adrenoceptor vs. the human alpha-2A and alpha 2B adrenoceptors is 14-fold and 16-fold, respectively. The alpha-2C selectivity, and the very high affinity of [3H]-MK912 for the alpha-2C adrenoceptor subtype (KD = 86 pM) makes this radioligand a promising tool for studying the role of alpha-2C adrenoceptors in the human. A selection of antagonists useful for differentiating between the human alpha-2A, alpha-2B and alpha-2C adrenoceptor subtypes is discussed. PMID- 7996471 TI - Mechanisms of up-regulation of D2L dopamine receptors by agonists and antagonists in transfected HEK-293 cells. AB - Mechanisms underlying agonist- and antagonist-induced up-regulation in HEK-293 cells transfected to express D2 dopamine receptors were investigated. We have reported previously that exposure of cells to agonists and antagonists led to an increase in the density of receptors. The time course of up-regulation on exposure to (-)-sulpiride, a D2 dopamine-selective antagonist, was measured. A lag in the effect of antagonists not seen with up-regulation induced by exposure to agonists was observed. Effects of N-propylnorapomorphine were synergistic with those of cyclic AMP analogs, however, synergistic effects between (-)-sulpiride and cyclic AMP analogs were not observed. These findings suggest that separate mechanisms may be involved in agonist- and antagonist-induced up-regulation. Changes in mRNA levels did not appear to account for the increase in receptors after agonist or antagonist treatment. Results of experiments with cycloheximide, a protein-synthesis inhibitor, suggest that increased protein synthesis, and not decreased protein degradation, is responsible for up-regulation by both NPA and ( )-sulpiride. Studies monitoring receptor recovery after treatment with N ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline, an irreversible alkylating agent, suggest that rates of receptor incorporation into membranes are increased after treatment with either an agonist or an antagonist. PMID- 7996472 TI - Selective antagonism of opioid analgesia by a sigma system. AB - (+)Pentazocine antagonizes morphine analgesia as potently as its (-)-isomer, ruling out an opioid receptor mechanism of action and suggesting, which suggests a role for sigma 1 receptors. Systemic (+) pentazocine also reverses supraspinal or spinal morphine analgesia. 1,3-Di(2-tolyl)guanidine, a sigma ligand with no appreciable opioid receptor affinity, antagonizes morphine analgesia. The actions of both (+)pentazocine and 1,3-di(2-tolyl)guanidine are reversed by haloperidol, which has high affinity for both sigma and D2 receptors, but not by the D2 selective antagonist (-)sulpiride, which lacks activity at sigma sites. The antiopioid sigma system is tonically active. Haloperidol, but not (-)sulpiride, decreases morphine ED50 almost 2-fold. The antiopioid system modulates only mu analgesia. Unlike analgesia, (+)pentazocine does not influence morphine's inhibition of gastrointestinal transit or lethality. (+)Pentazocine also antagonizes kappa 1, kappa 3 and delta analgesia through sigma mechanisms in a haloperidol-sensitive manner. (-)Sulpiride is inactive. Alone, haloperidol enhances kappa 1, kappa 3 and delta analgesia more dramatically than morphine, which indicates that the sigma system is active against all opioid analgesic systems. Sigma systems are responsible for some strain differences in kappa receptor sensitivity. Unlike CD-1 mice, BALB-C mice are relatively insensitive toward the kappa 1 agent U50,488H and the kappa 3 analgesic naloxone benzoylhydrazone. Blockade of the sigma system with haloperidol eliminates these strain differences. In conclusion, sigma 1 systems functionally antagonize opioid analgesia without affecting morphine's effects on gastrointestinal transit or lethality. The antiopioid sigma system is tonically active and is more active against kappa analgesia than mu.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7996474 TI - Autoregulation and monoamine interactions in the ventral tegmental area in the absence and presence of cocaine: a microdialysis study in freely moving rats. AB - Extracellular levels of norepinephrine (NE), dopamine (DA) and serotonin (5-HT) were measured simultaneously by microdialysis in the ventral tegmental area (VTA) of conscious rats, and locomotor activity was monitored. Extracellular NE, DA and 5-HT was increased by both local infusion (30 microM) and i.p. injection (20 and 40 mg/kg) of cocaine with 5-HT responding most rapidly. DA was the only amine that showed a significantly higher increase to the systemic cocaine dose of 40 mg/kg than 20 mg/kg, and a higher response to local cocaine (30 microM) than systemic cocaine (20 mg/kg). In the following experiments, the monoamine autoreceptor antagonists idazoxan (alpha-2, 100 microM), sulpiride (D2 DA/D3 DA, 10 microM) and methiothepin (5-HT1/5-HT2, 20 microM) were focally applied into the VTA before cocaine application. Idazoxan or methiothepin increased only local cocaine-induced NE or 5-HT output, whereas sulpiride increased both local and systemic cocaine-induced DA output, consonant with the importance of somatodendritic monoamine autoreceptors in addition to accumbens-VTA feedback pathways. Both idazoxan and methiothepin increased the basal output of all three amines without modifying cocaine (30 microM or 20 mg/kg)-induced output of DA/5 HT or NE/DA, whereas sulpiride promoted cocaine-induced NE output without modifying basal NE/5-HT output and cocaine-induced 5-HT output, implying complex interactions between monoamines. Idazoxan or methiothepin depressed, whereas sulpiride stimulated cocaine (20 mg/kg)-induced motor activity. The analysis of behavioral/neurochemical relationships revealed a negative correlation between dialysate NE output and motor activity in the cocaine alone and idazoxan/cocaine groups, and a positive correlation between dialysate DA output and motor activity in the sulpiride/cocaine and methiothepin/cocaine groups. PMID- 7996473 TI - Characterization of PD 121981- and CGP 42112-induced unmasking of low concentration effects of angiotensin II in rabbit abdominal aorta. AB - The unmasking of the low concentration effect of angiotensin II (AII) was identified within the concentration ranges of 10(-13) to 10(-11) M of AII by PD 121981 (5-diphenylacetyl-1-(4-methoxy-3-methylbenzyl)- 4,5,6,7-tetrahydro-1H imidazo[4,5-c]-pyridine-6-carboxylic acid) and 10(-12) to 3 x 10(-10) M of AII by CGP 42112 (nicotinic acid-Tyr-(N alpha-benzyl-oxycarbonyl-Arg)Lys-His-Pro-IIe OH), AT2 antagonists, in association with the ordinary contraction curve, i.e., high concentration effect (at 3 x 10(-10)-10(-6) M of AII), in the rabbit abdominal aorta. Thus, they showed clear biphasic features of AII-induced contraction curves. However, this was not the case for angiotensin I and angiotensin III. This PD 121981-evoked low concentration effect of AII was selectively inhibited by DuP 753 (0.01-1 nM), dithiothreitol (10 and 100 microM), pertussis toxin (50 and 300 ng/ml, for 2 hr), nifedipine (1 and 10 microM) and 8 (diethylamino)octyl 3,4,5-trimethoxybenzoate hydrochloride (1 and 3 microM), which suggests the receptors were the AT1 subtype. However, the high concentration effect of AII was not affected by these drugs within the concentration ranges used in the present studies. These myographic results were almost consistent with the features of the intracellular Ca++ changes. Thus, it was concluded that the receptors that mediate the low concentration effect of AII belong to the AT1 subtype. However, the current study did not determine the mechanism by which PD 121981 and CGP 42112 evoked the up-regulation of the AT1 receptors. PMID- 7996475 TI - Furosemide enhances the release of endothelial kinins, nitric oxide and prostacyclin. AB - Despite a wealth of data, the mechanism of the direct dilator effect of furosemide on the systemic arterial and venous systems is far from being satisfactorily understood. Therefore, we investigated whether furosemide is capable of stimulating the production of the endogenous vasodilators nitric oxide and prostacyclin in primary cultured bovine aortic endothelial cells by an enhanced synthesis and release of endothelium-derived kinins. Nitric oxide production was assessed in terms of intracellular guanosine cyclic-3',5' monophosphate accumulation; kinin and prostacyclin release were determined by specific radioimmunoassays. Furosemide concentration- and time-dependently increased the formation of nitric oxide and prostacyclin. Maximal increases of both autacoids were already obtained after a 5-min incubation with 3 x 10(-7) to 10(-6) mol/l of furosemide. In the same concentration range, furosemide led to an enhanced release of kinins into the supernatant of the cells. This observation was supported by the inhibitory effect of the specific B2 kinin receptor antagonist icatibant (Hoe 140) on the furosemide-induced increase of nitric oxide and prostacyclin. Thus the hemodynamic effects, and in particular the direct early dilator effect, of furosemide may be explained in part by an enhanced endothelial synthesis and release of bradykinin and related kinins, which in turn stimulates endothelial autacoid formation via B2 kinin receptor activation. PMID- 7996476 TI - Disruption of GABA-dependent chloride flux by cyclodienes and hexachlorocyclohexanes in primary cultures of cortical neurons. AB - The effect of convulsant and nonconvulsant hexachlorocyclohexane (HCH) isomers and cyclodienes on GABA-induced Cl- flux was studied in primary cultures of neocortical neurons by measuring the GABA-stimulated 36Cl- uptake. GABA induced a dose-dependent chloride uptake. The convulsant agents gamma-HCH and cyclodienes alpha-endosulfan, dieldrin and aldrin blocked this 36Cl- uptake. A total or partial inhibition of GABA-induced 36Cl- uptake was produced by the noncompetitive GABAA antagonists picrotoxinin (PTX) and pentylenetetrazol, respectively. The inhibitory potencies of 36Cl- uptake by the organochlorine compounds (alpha-endosulfan > dieldrin > gamma-HCH > aldrin) were well correlated with their inhibitory potencies of [35S]TBPS binding. Positive modulators of GABAergic function (flunitrazepam and phenobarbital) prevented the blocking of GABA-induced chloride uptake by PTX but not that induced by alpha-endosulfan. The depressant beta- and delta-HCH isomers produced a biphasic response, increasing or decreasing the GABA-stimulated chloride uptake, depending on the HCH isomer and GABA concentrations used. The present results support the idea of cyclodienes and gamma-HCH action at the GABAA receptor by interacting with the TBPS binding site. A different interaction of PTX and alpha-endosulfan in the same recognition site is also suggested. An increase of GABA-induced 36Cl- flux by beta- and delta HCH can account for the depressant activity of these compounds. This work also demonstrates the usefulness of primary neuronal cultures to perform functional studies of the GABAA receptor, taking into account allosteric interactions between the different recognition sites of the GABAA receptor. PMID- 7996477 TI - Effects of an antistroke agent MCl-186 on cerebral arachidonate cascade. AB - Activation of the cerebral arachidonate (AA) cascade is one of the major causes of edema and tissue injury in cerebral ischemia, particularly after reperfusion. The cascade produces toxic oxygen radicals responsible for peroxidative neurodegeneration and synthesizes, the potent edematous inducer, leukotrienes. The present study was undertaken to evaluate the effect of MCl-186 (3-methyl-1 phenyl-pyrazolin-5-one), a radical scavenger and antioxidant which has beneficial anti-ischemic actions, on the cerebral AA cascade. Postischemic treatment with MCl-186 (1.0 and 3.0 mg/kg i.v.) significantly inhibited the aggravation of cortical edema seen 60 min after recirculation following 30 min of ischemia in gerbils. An antilipoxygenase agent, FPL-55712 (7-[3-(4-acetyl-3-hydroxy-2 propylphenoxy)-2- hydroxypropoxy]-4-oxo-8-propyl-4H-1-benzopyran-2-carboxylic acid, monosodium salt; 10 mg/kg i.v.) or AA-861 ((2,3,5-trimethyl-6-(12-hydroxy 5,10-dodecadiynyl)-1,4-benzoquinon e; 60 mg/kg i.p.) was also effective in this model; however, indomethacin (4 mg/kg i.p.), a cyclooxygenase inhibitor, was ineffective. Concomitant treatment with MCl-186 (0.1-3.0 mg/kg i.v.) remarkably inhibited the swelling observed 24 hr after cortical infusion of AA (80 micrograms) in rats. Similarly, antilipoxygenase agents clearly inhibited the AA induced edema. Furthermore, postischemic treatment with MCl-186 (0.3-3.0 mg/kg i.v.) inhibited the facilitation of cerebral leukotriene synthesis seen 15 min after recirculation following 30 min of ischemia in gerbils. These findings suggest that the site of action of MCl-186 as an anti-ischemic agent may be closely associated with the cerebral AA cascade, especially the lipoxygenase system, activated by ischemia-reperfusion. PMID- 7996478 TI - Binding affinity and selectivity of opioids at mu, delta and kappa receptors in monkey brain membranes. AB - The binding parameters of radiolabeled DAMGO (mu), DPDPE and pCl-DPDPE (delta) and 5 alpha, 7 alpha, 8 beta-N-methyl-N-[7-(1- pyrrolidinyl)-1-oxaspiro(4,5)dec-8 yl]benzeneacetamide (also known as U69593, kappa) and the affinity and selectivity profiles of various opioid agonists and antagonists at the three opioid receptor types were determined in membranes from brain cortex of rhesus monkey. Among the 10 opioids with established mu-selective actions, etonitazene inhibited the binding of [3H]DAMGO with a Ki of 0.02 nM (0.01 nM without sodium) and exhibited mu/delta and mu/kappa selectivities of 8800 and 11,650, respectively. DAMGO had a Ki of 1.23 nM and was about 500-fold more selective at mu receptors compared with delta and kappa sites. Other mu opioids with higher than 100-fold binding selectivity were fentanil and sufentanil. Highly selective delta opioids were DPDPE, deltorphin II and naltrindole. With the exception of N,N-diallyl-Tyr-Aib-Aib-Phe-Leu-OH, all investigated putative delta opioids bound to delta sites with low Kis, i.e., 0.04 nM, 0.13 nM and 1.4 nM for naltrindole, (+/-)-4-[(alpha-R*)-alpha-((2S*,5R*)-4-allyl-2,5-dimethyl-1-piperazinyl) -3- hydroxybenzyl]-N,N-diethylbenzamide and DPDPE, respectively. In this series, the displacement of [3H]pCl-DPDPE yielded results similar to those obtained with [3H]DPDPE. With nanomolar Kis of 0.70, 0.89, 0.25 and 0.06, respectively, the highest kappa selectivity was displayed by (trans)-(+/-)-3,4-dichloro-N-methyl- N [2-(1-pyrrolidinyl)-cyclohexyl]benzeneacetamide and U69593, followed by dynorphin 1-13 and norbinaltorphimine.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7996479 TI - Muscarinic receptors involved in modulation of norepinephrine release and vasodilatation in guinea pig carotid arteries. AB - Acetylcholine (ACh, 1-50 microM) and carbachol (1-10 microM) concentration dependently enhanced the electrically evoked tritium overflow in guinea pig carotid arteries preincubated with [3H]norepinephrine (NE). However, lower concentrations of ACh and carbachol (0.05 and 0.1 microM) slightly reduced this overflow. Phentolamine (1 microM) potentiated the inhibitory and reduced the facilitatory effects of ACh, whereas hexamethonium (300 microM) did not modify either effect. Several muscarinic receptor antagonists shifted both ACh effects to the right. The order of potencies (apparent pKb values) was, for the facilitatory effect, atropine (10.14) > pirenzepine (8.66) > p-fluoro hexahydrosila-difenidol (p-F-HHSiD) (6.82) > or = to methoctramine (6.33), and the order for the inhibitory effect in the presence of phenotolamine was atropine (10.00) > methoctramine (7.86) > or = to AF-DX 116 (7.70) > pirenzepine (6.72) > p-F-HHSiD (6.00). ACh (0.01-10 microM) induced endothelium-dependent vasodilatation in perfused segments of guinea pig carotid arteries, and this effect was competitively inhibited by the above-mentioned muscarinic receptor antagonists. The order of potencies (pA2 values) was atropine (9.96) > p-F-HHSiD (8.05) > pirenzepine (7.64) > methoctramine (6.83). These results suggest that the noradrenergic nerve endings in guinea pig carotid arteries possess M2 inhibitory and M1 facilitatory muscarinic receptors that modulate NE release, and the endothelial cells possess M3 muscarinic receptors that mediate ACh-induced vasodilatation. PMID- 7996480 TI - Evidence that ACTH secretion is regulated by serotonin2A/2C (5-HT2A/2C) receptors. AB - The present study characterized the serotonin (5-HT) receptor subtypes mediating adrenal corticotropic hormone (ACTH) and corticosterone responses to 5-HT agonists in conscious rats. The 5-HT2A/5-HT2C agonist (+/-(-)1-(2,5-dimethoxy-4 iodophenyl)-2-aminopropane HC1 (DOI) increased plasma ACTH and corticosterone in a dose-dependent manner. The 5-HT2A/5-HT2C antagonist ritanserin (0.01 and 0.1 mg/kg sc) inhibited the DOI-induced increase in plasma ACTH, but not corticosterone. Low doses of spiperone (0.01 and 0.1 mg/kg sc) significantly reduced the ACTH response to DOI. Because spiperone has a higher affinity for 5 HT2A than 5-HT2C receptors, these data suggest that DOI stimulates ACTH secretion through 5-HT2A receptors. 5-methoxy-3-[1,2,3,4-tetrahydro-4-pyridinyl]-1H-indole (RU 24969) is a potent 5-HT1A/1B and moderate 5-HT2C agonist that also has been suggested to release 5-HT. However, p-chlorophenylalanine (PCPA) did not reduce the effect of RU 24969 on plasma ACTH, suggesting that RU 24969 only acts as a direct agonist. 6-methyl-1-[1-methylethyl]ergoline-8-carboxylic acid (LY53857) injected into the lateral cerebral ventricles (i.c.v.) inhibited the ACTH, but not corticosterone response to peripheral injection of RU 24969, suggesting that central 5-HT2A/2C receptors mediate the ACTH response. LY53857 injection (i.c.v.) also inhibited the effect of p-chloroamphetamine (i.c.v.) on plasma ACTH. However, the corticosterone response was not inhibited by LY53857, suggesting a distinct location of 5-HT receptors regulating corticosterone secretion.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7996481 TI - Increased plasma atrial natriuretic peptide after acute injection of alcohol in rats. AB - A number of mechanisms may be involved in the protective effect of low ethanol (ETOH) consumption on the development of the age-dependent hypertension in both human and experimental animals. It was the objective of the present study to test the hypothesis that acute administration of low doses of ETOH would increase the plasma content of atrial natriuretic peptide (ANP), a hormone known to decrease blood pressure. Plasma ANP levels were increased significantly within 15 min after the i.p. injection of 1 or 2 g of ETOH/kg b.wt. The increase in plasma ANP was more pronounced and longer lasting after the i.p. injection of 2 rather than 1 g of ETOH/kg b.wt. This increase in plasma ANP level was associated with a rapid decrease of atrial ANP, but not of ventricular ANP which on the contrary was significantly elevated at 120 min postinjection. It has been suggested that opioids could play a significant role in controlling ANP release. In fact, circulating levels of beta-endorphin were also rapidly increased after the ETOH injection, with a time-course pattern similar to that of ANP. Furthermore, a highly positive correlation was found between the ETOH-induced changes of plasma ANP and beta-endorphin contents. Significant increases in plasma corticosterone and adrenocorticotropic hormone, but not aldosterone contents, were observed after the i.p. injection of 2 g of ETOH/kg b.wt., whereas plasma arginine vasopressin levels were significantly decreased at 15 but not at 120 min postethanol. There was no significant elevation in blood pressure during the 120 min experimental period, although a small tachycardia did develop in the ETOH treated animals. Thus, acute in vivo administration of ETOH increased plasma ANP content in a dose-dependent manner and may play a role in the "protective" effect of low ETOH consumption in the development of the age-dependent hypertension. PMID- 7996482 TI - A possible mechanism of action of a new potassium channel opener, AL0671, on lipid metabolism in obese Zucker rats. AB - Antihypertensive drugs are expected to have a lipid-lowering effect for use in treating ischemic heart disease. We evaluated the effect of (+)-N-(6-amino-3 pyridil)-N'-[(1S,2R,4R)-bicyclo-[2.2.1]hept-2-yl] -N"- cyanoguanidine hydrochloride (AL0671), a newly synthesized cyanoguanidine-derivative potassium channel opener, on serum lipid and lipoprotein levels in obese Zucker rats, a genetically engineered model of type IV hyperlipidemia. AL0671 dose-dependently decreased systolic blood pressure in obese Zucker rats. Serial administration (for 1 or 2 weeks) of AL0671 (5 mg/kg/day) significantly decreased serum total triglyceride, chylomicron and very-low-density lipoprotein levels with increasing high-density lipoprotein cholesterol, whereas low-density lipoprotein levels did not change. AL0671 (5 mg/kg/day) increased lipoprotein lipase activities 4-fold and hepatic triglyceride lipase activities 3-fold in postheparin plasma. Another urea-derivative compound, AL0674, whose potassium channel-opening activity is diminished, did not affect serum lipid and lipoprotein levels. These results suggested that AL0671 activates both lipoprotein lipase and hepatic triglyceride lipase activities through its potassium channel-opening activity followed by decreasing triglyceride-rich lipoproteins in genetically obese hyperlipemic rats. Therefore, AL0671 might be beneficial in the treatment of hypertensive patients with hypertriglyceridemia (probably with insulin resistance). PMID- 7996483 TI - Lecithinized superoxide dismutase enhances its pharmacologic potency by increasing its cell membrane affinity. AB - We performed the present study to clarify whether lecithinized superoxide dismutase (PC-SOD) enhanced its pharmacologic potency by increasing its cell membrane affinity. PC-SOD, in which 4 molecules of a phosphatidylcholine (PC) derivative were covalently bound to each dimer of recombinant human CuZn-SOD (rhCuZn-SOD), was shown to have a high membrane affinity using a laser confocal imaging technique. PC-SOD efficiently scavenged superoxide anion (O2-) produced by phorbol myristate acetate (PMA)-stimulated human neutrophils (IC50 0.60 U/ml), and it exerted a dose-dependent scavenging effect (IC50 1.27 U/ml) even when the neutrophils were washed after incubation with PC-SOD. In contrast, neither unmodified SOD nor polyethylene glycol-bound SOD (PEG-SOD) showed a scavenging effect for washed neutrophils, even at a high concentration (100 U/ml). PC-SOD also showed a strong protective effect against human vascular endothelial cell damage caused by O2- generated by stimulated neutrophils, and PC-SOD was approximately 100-fold more potent than unmodified SOD (in vitro IC50 100 U/ml for PC-SOD and > 10,000 U/ml for unmodified SOD). Moreover, PC-SOD (50,000 U/kg) had an inhibitory effect on ischemia-reperfusion paw edema in mice, whereas neither unmodified SOD nor PEG-SOD had any effect. These results suggest that PC SOD (designed to target for cell membranes) exerted a far higher pharmacologic activity by increasing cell membrane affinity than unmodified SOD and may be potentially useful for various clinical applications. PMID- 7996484 TI - High affinity cocaine recognition sites on the dopamine transporter are elevated in fatal cocaine overdose victims. AB - Cocaine mediates its powerful reinforcement by binding to recognition sites on the dopamine (DA) transporter. The pharmacological identity of cocaine recognition sites and their relevance to dopamine transport function has remained unclear. Ligand binding studies with transport inhibitors and cocaine congeners have provided evidence for multiple sites or "states" of the DA transporter. The potent cocaine congener [3H]WIN 35,428 ((CFT), 2B-carbomethoxy-3 beta-(4 fluorophenyl)-tropane) has been shown to recognize high and low affinity binding sites on the DA transporter. We have used [3H]WIN 35,428 to map and quantify the high affinity cocaine recognition site on the DA transporter in victims of fatal cocaine overdose. Region-of-interest densitometric analysis of the autoradiograms demonstrated a 2- to 3-fold elevation in the apparent density of [3H]WIN 35,428 binding in particular sectors of the striatum from victims of cocaine overdose as compared to age-matched and drug-free control subjects. The most marked increase in [3H]WIN 35,428 binding was seen in the nucleus accumbens. The apparent increase in the density of high affinity sites was confirmed by saturation binding analysis of [3H]WIN 35,428 to putamen membranes. Saturation analysis revealed high and low affinity binding components with affinities (KD values) of 4.3 +/- 1.2 and 84.7 +/- 19.7 nM (mean +/- S.E.) and densities of 9.9 +/- 4.0 and 193.0 +/- 28.6 pmol/g of tissue, respectively.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7996485 TI - Analysis of delta-opioid receptor activities stably expressed in CHO cell lines: function of receptor density? AB - The question of whether short- and long-term opioid agonist activities could be affected by receptor density is being addressed with Chinese hamster ovary (CHO) cell lines stably expressing delta-opioid receptors. CHO cells expressing different levels of delta-opioid binding sites were isolated and characterized. The opioid binding sites in these cell lines have stereoselective high affinity for 3H-diprenorphine (0.18 to 0.91 nM), with agonist binding sensitive to both Na+ and GTP gamma S, and are of the delta-2-opioid receptor subtype. This is conclude from observations that the delta-2-opioid receptor-selective agonist naltriben (NTB) has higher affinity than the delta-1-opioid receptor-selective agonist 7-benzylidenenaltrexone (BNTX). It also could be demonstrated that delta opioid agonists inhibited forskolin-stimulated intracellular 3H-cAMP production and that agonist inhibition could be blocked by pretreating cells with pertussis toxin. Again, NTB is more potent than BNTX or naloxone in reversing DPDPE inhibition of intracellular 3H-cAMP production. When the ability of [D-Ala2,D Leu5]enkephalin (DADLE) to regulate adenylyl cyclase activity was examined in three separate CHO cell lines: CHODORX1-15, CHODORX1-8 and CHODORX1-4, which express 1.42 +/- 0.08, 0.74 +/- 0.07 and 0.27 +/- 0.04 pmol/mg-protein of receptor, respectively, maximal inhibitory levels in clones X1-15 and X1-8 were similar, whereas maximal inhibitory level for clone X1-4 was 66% of the other two clones. However, when maximal inhibitory levels of other opioid receptor selective agonists were examined, different levels of inhibition were observed among these three CHO clones.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7996486 TI - DNA as a critical target in toxic cell death: enhancement of dimethylnitrosamine cytotoxicity by DNA repair inhibitors. AB - Our working hypothesis states that DNA damage is a critical step in toxic cell death. The DNA hypothesis was tested in cultured mouse hepatocytes by examining whether inhibitors of DNA repair would increase dimethylnitrosamine toxicity and DNA damage in parallel. Inhibitors were chosen for selectivity toward DNA polymerase alpha (aphidicolin, myricetin), DNA ligase (ethidium bromide), or multiple repair enzymes (ara-C, doxorubicin). Dimethylnitrosamine caused concentration-dependent DNA damage at 6 hr and cell death at 24 hr (35% ALT release vs. 8.8% in control cultured hepatocytes). Each repair inhibitor increased dimethylnitrosamine-induced DNA damage and toxic cell death in parallel. Doxorubicin maximally elevated DNA fragmentation and toxicity (57% ALT release). Repair inhibitors alone failed to damage DNA or cause cell death in this model system. These data support the hypothesis that DNA damage is an early causal event in toxic cell death caused by alkylating hepatotoxicants. PMID- 7996487 TI - Neuroanatomical specificity and dose dependence in the time course of imipramine induced beta adrenergic receptor down-regulation in rat brain. AB - The time course of beta adrenergic receptor adaptation in response to chronic imipramine treatment (10 or 20 mg/kg) was assessed by quantitative autoradiographic analysis of 125I-pindolol binding in rat brain. Binding of the radioligand was assessed in 18 brain areas, including subregions of the hippocampus, amygdala, septum, hypothalamus and specific cerebral cortical regions. After only 2 days treatment with imipramine at a dose of 20 mg/kg, select cortical regions exhibited a reduction in 125I-pindolol binding. These rapidly adapting cortical regions included the medial prefrontal, lateral frontal, ventrolateral orbital and piriform cortices. After 7 or 21 days treatment with imipramine at 20 mg/kg, 16 of 18 brain regions examined exhibited significant reduction in 125I-pindolol binding. The only regions examined that did not show reduced 125I-pindolol binding for these treatment conditions were the caudate-putamen and anterior hypothalamic area. After 2 days treatment with 10 mg/kg of imipramine, down-regulation of beta adrenergic receptors was not observed in any region. After 7 days treatment with 10 mg/kg, down-regulation of beta adrenergic receptor binding was found only in certain cortical regions: medial prefrontal, lateral frontal, ventrolateral orbital and piriform cortices. Thus, the cortical regions that were most rapidly affected with the 20 mg/kg dose of imipramine (i.e., after 2 days) were also the first to respond with the 10 mg/kg dose of the drug. After 21 days treatment with imipramine at 10 mg/kg, 125I pindolol binding was reduced in 13 of the 18 regions examined.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7996488 TI - Biochemical and pharmacological characterization of the cyclooxygenase activity of human blood prostaglandin endoperoxide synthases. AB - The aim of our study was to characterize a model of human prostaglandin endoperoxide synthase-2 (PGHS-2) expression allowing the assessment of pharmacological inhibition in vitro and ex vivo. Heparinized human whole blood samples were incubated with lipopolysaccharide (LPS, 0.1-50 micrograms/ml) for 0 to 24 hr at 37 degrees C. The contribution of platelet PGHS-1 was suppressed by either pretreating the subjects with aspirin (300 mg 48 hr before sampling) or adding aspirin (10 micrograms/ml) in vitro at time 0. PGE2 was measured by radioimmunoassay. LPS induced expression of cyclooxygenase activity in a time- and concentration-dependent fashion. After 24 hr at 10 micrograms/ml LPS, PGE2 production averaged 12.1 +/- 6.2 ng/ml (mean +/- S.D., n = 7). Cyclooxygenase activity increased in parallel with the mass of a monocyte protein doublet analyzed by Western blot using antibodies directed against the carboxyl-terminal portion of human PGHS-2. Dexamethasone (2 microM) inhibited LPS-induced PGE2 production by 96 +/- 4% (mean +/- S.D., n = 3). Four different inhibitors were tested in vitro on the cyclooxygenase activity of LPS-induced monocyte PGH-2 and thrombin-stimulated platelet PGHS-1. IC50 values (microM) for inhibition of PGHS 1 and PGHS-2 were: indomethacin, 0.70 +/- 0.20 vs 0.36 +/- 0.10 (P < .05); S indobufen, 0.64 +/- 0.22 vs. 14.9 +/- 8 (P < .05), R-indobufen, 38 +/- 18 vs. 230 +/- 68 (P < .01), 6-methoxy-2-naphthyl acetic acid (the active metabolite of nabumetone), 278 +/- 96 vs. 187 +/- 96.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7996490 TI - Fluid above forty--facile situation? PMID- 7996489 TI - Alteration of G protein levels in antigen-challenged guinea pigs. AB - To elucidate the mechanism(s) of altered responses of various receptors observed in asthma, we examined levels of G proteins in lung membranes isolated from guinea pigs at various stages of experimental asthma. We found that levels of Gi2 alpha and Gq alpha increase after multiple exposures to aerosolized antigen but not after a single exposure. Levels of Gi1 alpha, Gs alpha and G beta did not change under these experimental conditions. Tracheas from these animals exhibited hyperresponsive muscarinic bronchoconstriction and hyporesponsive beta adrenoceptor-mediated relaxation of endothelin-preconstricted tracheas as measured by an ex vivo isometric assay. No changes in numbers or affinities of membrane M3 muscarinic and beta-2 adrenergic receptors were detected as measured by binding of [3H]QNB and [125I]CYP, respectively. The impairment of beta adrenoceptor-mediated relaxation of tracheas isolated from animals treated by multiple challenges was reversed by the pretreatment of tracheas with pertussis toxin. On the other hand, the carbamylcholine-stimulated GTPase activity was higher in lung membranes isolated from animals in the multiple challenge group and was blocked by anti-Gq alpha protein antibody. Taken together, our present observations suggest that an underlying mechanism of altered receptor responses associated with asthma is in part due to increased expression of Gi2 alpha and Gq alpha proteins, leading to altered coupling of receptors to effector systems. PMID- 7996491 TI - The flip side of Ayurveda. PMID- 7996492 TI - Biochemical changes in polymorphonuclear leucocytes in diabetic patients. AB - A study on the functional ability of polymorphonuclear leucocytes (PMNL) indicates that the total lysosomal enzyme levels viz. Beta-glucuronidase, lysozyme, acid phosphatase and alkaline phosphatase were not altered in diabetics, compared to that in control subjects. However, the findings also reveal that the release of these lysosomal enzymes in response to a particulate stimulus is impaired in diabetics. This suggests that the bactericidal capacity of these cells, which are involved in phagocytosis, is impaired in diabetics, making them more vulnerable to infections. PMID- 7996493 TI - Comparative pathogenicity of Trichomonas vaginalis isolated from symptomatic and asymptomatic cases. AB - Pathogenicity of 19 isolates of Trichomonas vaginalis obtained from vaginal specimens were studied in the murine model by intraperitoneal inoculation. Sixteen isolates were recovered from the females with various clinical conditions and 3 isolates were from normal healthy females. Pathogenicity level of these isolates were studied by inoculating 5 mice per isolate through intraperitoneal route and the animals were sacrificed on the 10th day post-inoculation. In general, all the isolates recovered produced infection in mice. On comparison with the reference strain obtained from Hoechst India Ltd., seven isolates recovered from symptomatic cases and one strain from healthy females produced severe infection in mice. Though variation in the pathogenicity level was observed among the isolates, a definite correlation between the clinical picture in the natural host and pathogenicity in mice was not observed. PMID- 7996494 TI - Exudative pleural effusions in patients over forty years of age--an analysis of seventy-six patients. AB - A prospective study of 76 consecutive patients over the age of 40 years, with exudative pleural effusion, was undertaken to determine the common causes of such a clinical condition. Malignant pleural effusions were the most common in this series, found in 49 patients (64.47%), all but one being metastatic from elsewhere. Forty were secondary to a carcinoma of the bronchus, 3 from carcinoma of the breast, 1 each from carcinoma of the ovary, oesophagus, and larynx; lymphoma accounted for the remaining 2. Infective causes accounted for 24 of the effusions (31.57%). Of the infections, tuberculosis was the most common, accounting for 17 of the 24. Other infective causes included bacterial empyemas in 4, ruptured amoebic liver abscess in 2, and actinomycosis in 1. Pancreatitis, pulmonary thromboembolism, and a post-cardiotomy syndrome were diagnosed in 1 patient each, while the diagnosis remained unknown in the remaining 5 patients. In 2 patients the diagnosis was made on autopsy. PMID- 7996495 TI - Ligation of internal iliac arteries for control of pelvic haemorrhage. AB - This is a retrospective review of the internal iliac ligations (IAL) done over a period of 3 years. Both gynaecological and obstetric cases were considered. A total of 46 ligations were performed. The additional treatment required was hysterectomy to control haemorrhage. Intra-and post-operative complications were noted. A comparative review of the effectiveness of IAL in different situations is done and alternative modalities of treatment are considered. PMID- 7996496 TI - A histomorphologic and ultrastructural study of the malignant tumours of the renal pelvis. AB - The study was carried at two different centres. Only 9 cases of primary malignant tumours of the renal pelvis could be collected during the period of 7 years (1984 1990). Renal pelvis malignancies constituted 0.21% of all the malignancies and 12.16% of all the malignant growths of the kidney (9 out of 74 cases). The age of these patients ranged from 24 to 70 years; the mean being 41.7 years. Male/female ratio was 8:1. Common triad of complaints (pain, haematuria and lump) was noticed in 22.2% of patients. Individually they were noticed in 77.8%, 66.7% and 44.4% of patients respectively. Transitional cell carcinoma was the commonest, seen in 7 patients (77.8%) whereas squamous cell carcinoma and adenocarcinoma were noticed in one patient (11.1%) each. Hydronephrosis, chronic pyelonephritis and nephrolithiasis were noticed in 66.7%, 44.4% and 22.2% of patients respectively. Ultrastructural study of urothelial tumours revealed tumour cells in various stages of differentiation with loss of intercellular junctions and dense collection of rough endopasmic reticulum fibrils around the nucleus. PMID- 7996497 TI - Surgery for thyroid goiter in western India. A prospective analysis of 334 cases. AB - 334 consecutive cases of thyroid swellings operated by a single surgical unit over 9 years have been analysed prospectively. There was a female preponderence (4.39:1). The swellings were clinically differentiated into uninodular (39.52%), multinodular (47.31%) and diffuse (13.17%). Hyperthyroidism was manifested in 49 cases (14.67%). Pressure symptoms were present in only 1.5% cases. FNAC detected malignancy in 14 of 162 cases (8.64%). The initial 100 cases were operated upon by standard Lahey's technique and the latter 234 by modified technique described by Bapat et al for benign thyroid disease. Operations performed included nodulectomies (5.39%), hemithyroidectomies (41.92%), partial thyroidectomies (25.75%), subtotal (25.45%) and near total thyroidectomies (1.5%). Post-operative complications were higher in the first group and included unilateral cord palsies 5 (5%). hypocalcemia-4 (4%) hypoparathyroidism-1 (1%) haemorrhage-1 (1%) and mortality-1 (1%) vis a vis cord palsies-2 (0.85%), hypocalcemia-3 (1.28%), hypoparathyroidism-1 (0.43%) and there was no mortality. Histopathology revealed 83 (24.85%) colloid goiters, 193 (57.78%) nodular goiters, 21 (6.29%) follicular adenomas, 7 (2.10%) cases of thyroiditis and 30 (8.98%) malignancies. This study reveals the lower incidence of RLN palsy after modified thyroidectomies, and a low incidence of malignancy. PMID- 7996498 TI - Cadaveric transplantation. AB - Transplantation is already the optimum treatment for terminal renal failure. Donor organ shortage means that there are large number of patients on dialysis awaiting this treatment. This has in some countries led to unacceptable unscrupulous practices of live non-related graft donation. The outcome of graft and patient after transplantation has improved significantly based on a better understanding of immunopathology, immunosuppression and tissue typing. The future is promising and xenografting may well solve the organ shortage but undoubtedly will raise other issues. PMID- 7996499 TI - Adenoid cystic carcinoma of the cervix. AB - Adenoid cystic carcinoma constitute around 0.4 to 1.7% of all carcinomas of cervix. It generally presents in elderly age group, however few cases in younger age have also been reported. Majority of cases present in early stage. Though concluding statement regarding the results cannot be made from the cases accumulated from the various reported series, nonetheless this review shows that radiotherapy too is effective in early stage and even in stage I results with radiotherapy appear better than surgery. In advanced stage outcome is invariably poor. In early stage main pattern of failure is distant metastasis. Both local and distant failure are observed in stage III and IV. Though lung is the commonest site of metastases (51%), abdominal cavity and brain are also found to be involved in some cases. Limited experience shows effectiveness of high doses of cisplatin and multiagent chemotherapy. Cases of early stage disease having risk for metastases and local failure should be identified and managed with multimodality treatment using surgery for bulky disease with post-operative radiotherapy and chemotherapy. In advanced stages combination of chemotherapy and radiotherapy is required. Exenterative surgery for central failure has been used effectively. Overall no evidence of disease rate is found to be about 48%, with mean follow-up of 39 months. PMID- 7996500 TI - Cervical approach for repair of congenital tracheo-esophageal fistula presenting in an adult. AB - Congenital tracheo-esophageal fistula without esophageal atresia was diagnosed on barium swallow radiography and esophagoscopy findings in an adult patient presenting with difficult in swallowing. The fistulous opening seen on the anterior wall of the esophagus led to the trachea. On bronchoscopy, the tracheal opening was located posteriorly 5 cm below the vocal cords. Successful repair was undertaken via a left cervical approach. The anatomical and developmental basis for the preferred approach is discussed with a brief literature review on the subject. PMID- 7996501 TI - The Proteus syndrome. AB - A race case of Proteus syndrome is presented. The main features of this hamartomatous condition are partial gigantism of hands and feet, hemihypertrophy, subcutaneous masses, epidermal nevi and bony abnormalities. The condition is extremely rare. Though the child had severe cosmetic disability, motor intellectual and language development was found to be normal. PMID- 7996502 TI - Dural cavernous haemangioma of posterior cranial fossa. AB - A rare case of extracerebral dural cavernous angioma sited near the sigmoid sinus is reported. This 60 yr old male patient gave history of episodic ataxia of left sided limbs experienced twice on same day and occasional giddiness. Examination did not reveal any findings. A mass was diagnosed on CT Scan following which angiography was carried out. The features matched with those of a meningioma. Retro-sigmoid craniectomy was performed. Occipital artery was coagulated. Tumor was dissected out. Post-operative course of the patient was uneventful. Histopathology revealed that the mass was a cavernous haemangioma. PMID- 7996503 TI - Malformation of lung in neonates (lobectomy for congenital lobar emphysema and lung cyst). AB - Congenital lobar emphysema (CLE) and lung cyst--congenital cystic adenomatoid malformation (CCAM) are rare conditions in the neonatal period. Lobectomy is the only treatment for these conditions. We had 4 neonates, seen over a period of two years, who had congenital lobar emphysema and one neonate who had lung cyst. All babies had undergone lobectomy. Their anaesthetic management is discussed here. PMID- 7996505 TI - The mythology of modern medicine--III. Microbes and man--Part 2. PMID- 7996506 TI - Statistics in medical research--III. Correlation and regression analysis. PMID- 7996504 TI - Fraser syndrome. AB - Fraser Syndrome is a rare disorder with only a few cases having been described in Indian literature. We report here a case of a patient aged 16 yr present with primary amenorrhea which is a very unusual mode of presentation. Multiple associated anomalies were present including those of eyelids, eyebrow, face, fingers and genitalia. Chromosome analysis revealed a normal female karyotype. Pituitary gonadotropins were within normal range. PMID- 7996507 TI - A constraint-based lexicalist account of the subject/object attachment preference. AB - When a noun phrase could either be the object of the preceding verb or the subject of a new clause or a sentence complement, readers and listeners show a strong preference to parse the noun phrase as the object of the verb. This can result in clear garden paths for sentences such as The student read the book was stolen and While the student read the book was stolen. Even when the verb does not permit a noun phrase complement, some processing difficulty is still found. This has led some theorists to propose models in which initial attachments are lexically blind, with lexical information subsequently used as a filter to evaluate and revise initial analyses. In contrast, we show that these results emerge naturally from constraint-based lexicalist models. We present a modeling experiment with a simple recurrent network that was trained to predict upcoming complements for a sample of verbs taken from the Penn Treebank corpus. The model exhibits an object bias and it also shows effects of verb frequency which are similar to those found in the psycholinguistic literature. PMID- 7996508 TI - Prosody and the processing of filler-gap sentences. AB - This study was designed to explore the effects of linguistic prosody on the processing of "filler-gap" sentences. We designed two experiments to determine first whether the sentence processor uses information contained in the prosodic contour of an utterance during on-line processing, and second the form that information may take. In Experiment 1, we found that prosody apparently influences when listeners posit gaps on-line. In Experiment 2, we obtained acoustic evidence that gaps are represented in the prosodic contour of an utterance. The results of this study support a view in which prosody contributes very early to on-line structure building mechanisms during sentence processing. PMID- 7996510 TI - The need for preoperative leg angiography in fibula free flaps. AB - Among arterial anatomic conditions which will adversely affect the harvest of the fibula are 1) significant arteriosclerotic disease within the tibial-peroneal vessels; 2) peroneal arteria magna (PAM), a condition in which only the peroneal artery supplies the foot; and 3) absence of the peroneal artery, either congenitally or as an acquired defect. In each of these anatomic conditions, removal of the peroneal vessels and the fibula free flap will jeopardize either the donor leg, the fibula flap, or both. All patients considered for fibula flaps were evaluated with preoperative leg angiograms. In 28 consecutive patients evaluated with angiography for planned free-fibula flap reconstructions, 23 actually underwent free-fibula harvest. Angiographic abnormalities that altered the operative plan were found in seven (25 percent) patients. Four of the seven patients had vascular examinations prior to surgery with abnormal findings. Three of the seven (11 percent) patients with abnormal arterial anatomy had normal vascular examinations prior to surgery. Thus, if a preoperative angiogram had not routinely been done, the abnormal anatomy would not have been discovered until surgery. This could have resulted in an unusable flap in one patient, and an ischemic or gangrenous foot in two other patients. With this angiographic guidance, there were no vascular complications from harvest of the fibula. The routine use of preoperative bilateral leg angiography is recommended, or an alternative method of vessel imaging, in all patients evaluated for microvascular free-tissue transfer of the fibula. PMID- 7996509 TI - Functional localization in the brain with respect to syntactic processing. AB - This report describes some recent examinations of the ability of aphasic patients to construct syntactically governed dependency relations in real time. The data show that Wernicke's patients can link the elements of dependency relations in the same way as neurologically intact subjects, even for sentences that they do not understand. Broca's patients, by contrast, are shown to be unable to create such links, even for sentences that they do understand. These data underline the isolability of this stage of syntactic analysis and they suggest that comprehension limitations statable in syntactic terms can be traced to changes in cortically localizable processing resources. PMID- 7996511 TI - Mandibular reconstruction using computer-generated three-dimensional solid models. AB - In mandibular reconstruction, it is necessary to know the exact, three dimensional extent of the mandible and its defect; the bone graft must be the exact size and dimension of the defect, to assure a precise three-dimensional configuration of the mandible. Previously, the bone graft had to be reshaped during the operation by trial and error, often a time-consuming procedure. The operative procedure has been simulated in advance using three-dimensional, solid models, which has shortened the operating time required. PMID- 7996512 TI - The radial forearm flap: a reconstructive chameleon. AB - The authors present a ten-year series of consecutive one-stage reconstructions of defects following excision of malignant disease and of traumatic defects, using the radial forearm flap. Of the 155 radial forearm flaps performed, 144 were free flaps and 11 were pedicled flaps; 55 of the 144 free flaps were osteofasciocutaneous. Microvascular reconstructions with this versatile flap had a 98 percent success rate in this series. PMID- 7996513 TI - Free TRAM flap for lower-extremity reconstruction. AB - The usefulness of TRAM flaps is well-established. Their use in soft-tissue reconstruction of the lower limbs is illustrated. The flaps allow coverage of soft-tissue defects with good quality skin, and add bulk to enhance leg contour. Three cases are presented, and the advantages of this flap are discussed. PMID- 7996514 TI - Venous flaps for covering skin defects of the hand. AB - Thirty cases of skin defects of the hand were treated with 32 venous flaps. Seven of the flaps used were flow-through venous flaps (V-V type), in which venous blood flows in and out. Of the arterialized venous flaps into which arterial blood flows, the outflow in nine cases was anastomosed to a vein (A-V type), that in 15 cases to an artery (A-A type), and one flap had inflow only. Twenty-one of the flaps were completely successful, but seven resulted in partial and four in complete necrosis. Indications for V-V flaps are skin defects of small dorsal areas of the fingers, but this type of flap can also be used for skin defects in the dorsal area of the hand, if the number of veins anastomosed is increased. The A-V flap is especially indicated for covering multiple digital skin defects, while the best indication for A-A flaps is a skin defect on the lateral or volar side of the digit which requires simultaneous reconstruction of blood circulation. PMID- 7996515 TI - Results of one-stage penile reconstruction using an innervated radial osteocutaneous flap. AB - Reconstruction of the penis may be indicated in cases of traumatic or surgical amputation of the penis, congenital absence of the penis, micropenis, male pseudohermaphroditism, or transsexualism. Despite recent advances in microsurgery, which have improved the results of total penile reconstructions to a great extent, this operation remains one of the biggest challenges to reconstructive plastic surgeons. The authors have performed one-stage penile reconstruction in five patients since 1989, using an innervated radial forearm osteocutaneous flap. At follow-up (up to 46 months), all patients showed aesthetically acceptable results and good sensory recovery. The most common complications were related to the urethra, involving two fistulae and one urethral stricture. PMID- 7996516 TI - Spiral oblique retinacular ligament (SORL) mallet correction in a finger with a proximal interphalangeal joint transferred from a toe. AB - The use of a spiral oblique retinacular ligament (SORL) reconstruction is reported in a middle finger that had previously undergone reconstruction of the proximal interphalangeal (PIP) joint, using a free, vascularized, second-toe PIP joint transfer. The SORL procedure was applied for the reconstruction of the terminal tendon. A satisfactory postoperative range of joint mobility and stability was achieved. PMID- 7996517 TI - Identical rectus abdominis donor-site morbidity in compromised and healthy patients. AB - As microvascular capabilities improve, donor-site complications may become of greater concern. This has become an issue, particularly with the rectus abdominis muscle which is unique, as weakening of abdominal-wall integrity is always a potential problem. The author has reviewed all 50 of his pedicled and free-flap transfers of the rectus abdominis muscle, comparing healthy and chronically ill patients, for elective and emergent indications. Twelve percent of patients had donor-site complications, identical for both healthy and ill patients; 11.4 percent of pedicled flaps and 13.3 percent of free flaps had compromised outcomes. Three hernias occurred as major complications, which probably could not have been avoided. Nevertheless, these frequencies were within the range of expected complications, as with any muscle-flap donor site. The merit of this flap at the recipient site usually justified the risks and, in spite of appropriate risks and, in spite of appropriate trepidation regarding this donor site, the benefit of this flap should not be denied, even for the unhealthy patient. PMID- 7996518 TI - Trophism, tropism, and specificity in nerve regeneration. AB - Target-derived neurotrophic factors are of basic importance for survival of neurons. In the normal state, such neurotrophic factors, synthesized by the target tissues, are taken up by nerve terminals and transported by retrograde axonal transport in axons to the nerve-cell bodies to maintain their viability. After nerve injury, neurotrophic factors are synthesized by non-neuronal cells (Schwann cells and fibroblasts) in the nerve trunk, thereby supporting the outgrowth of axons. Neurite-outgrowth-promoting factors on cell surfaces (cell adhesion molecules, "recognition molecules") or in the extracellular matrix promote extension of the axons by providing an appropriate "adhesiveness" in the substrate. Both neurotrophic and neurite-outgrowth-promoting factors are essential for axonal growth after injury. Specificity in end-organ reinnervation is a complex phenomenon which may be based on physical factors at the zone of injury, as well as on molecular interaction between axons and substrate cells along the pathways and at the target level. Such processes may include molecular recognition of appropriate axons and maintenance of such axons by trophic mechanisms, as well as the pruning of inappropriate axons. The ultimate errors in target reinnervation are reflected in a cortical re-organization in the somatosensory cortex. The capacity of the brain to "reprogram" itself and adapt to this functional re-organization is critical for the ultimate recovery of functional sensory/motor function after nerve injuries. PMID- 7996519 TI - Outpatient pelvic laparotomy. AB - A population of generally healthy women underwent a variety of reproductive operations by pelvic laparotomy at an ambulatory surgical center. The techniques and safety of this approach are described. Of the 373 women, one experienced a major complication (ureteral injury), which was treated in the surgicenter. The patient recovered in the hospital, with no late adverse outcome. Two other women were hospitalized for intravenous fluid therapy because of persistent nausea and vomiting. No patients required blood transfusion or reoperation. Four women had minor complications that were treated outside the hospital. The rate of hospitalization was 0.8%; of major complications, 0.3%; of minor complications, 1.6%; and of total complications, 1.9%. In this population, 98% of the patients had no complication, and 99% did not need hospital care. Thus, outpatient pelvic laparotomy was found to be safe and cost effective. PMID- 7996521 TI - Incidence of actinomycosis associated with intrauterine devices. AB - The incidence of intrauterine device (IUD)-associated cervicovaginal actinomycosis was evaluated. Papanicolaou-stained cervicovaginal smears from 1,520 women with IUDs were reviewed for the presence of Actinomyces-like organisms. The overall colonization rate was 11.4%. The colonization rates for the Progestasert, plastic IUDs and copper IUDs were 14.3%, 10.8% and 6.69%, respectively. The colonization rate appeared to increase with the duration of IUD use. The relatively high cervicovaginal Actinomyces colonization rate suggests that all patients with IUDs should undergo annual cytologic smears, with specific attention given to the presence of Actinomyces-like organisms. PMID- 7996520 TI - Morphologic assessment of endometrium overlying submucosal leiomyomas. AB - The effect of submucosal leiomyomas on endometrial structure in women with symptomatic clinical findings was studied retrospectively. The endometrial histology from 13 hysterectomies for uterine leiomyomas was examined using three 2-mm sections of endometrium (one overlying a submucosal leiomyoma and two without underlying leiomyomas). Endometrial thickness, gland number and appearance, vessel number and diameter, and stromal inflammation were assessed. The thickness of the myometrium between the leiomyoma and the overlying 2-mm section of endometrium analyzed was also evaluated. The control group consisted of seven nonmyomatous uteri removed for benign disease. Analysis of the endometrium with underlying submucosal leiomyomas identified two groups using endometrial gland number as the criterion for this division. Five cases (group A) were found to have no endometrial glands, while the remaining eight (group B) had an average gland number of 74.5 per 2-mm section of endometrium. The mean gland number for the control group was 82.6, showing no significant difference from group B. Group A had an average endometrial area (2-mm thickness) of 0.38 mm2, and group B had an average area of 4.47 mm2, for a significant difference (t = 3.76, P = .007). Comparison of the two groups with the control group (mean area, 4.71 mm2) showed a significant difference in endometrial area only with group A (t = -7.64, P < .0005). A significant difference (t = -2.93, P = .019) was observed in the analysis of the thickness of the myometrium between the leiomyoma and overlying endometrium between groups A (mean thickness, 0.53 mm) and B (mean thickness, 1.70 mm).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7996522 TI - Amnioinfusion. A review. AB - The recent obstetric literature reports on various applications of amnioinfusion that have been used in an attempt to improve maternal and neonatal outcome. This paper reviews the indications, techniques, clinical benefits and hazards associated with the use of this procedure. PMID- 7996523 TI - Compliance-weight deficit index. Combining umbilical artery resistance and growth deficit for predicting intrauterine growth retardation and poor perinatal outcome. AB - One hundred sixty-six patients underwent examination of the umbilical artery (UA) by continuous wave Doppler ultrasound one week prior to delivery. The UA compliance deficit (CD) and weight deficit (WD) were combined into an index (CWDI) by a formula based on the Pythagorean Theorem. CWDI represents the hypotenuse, and CD and WD represent the two perpendicular lines of a triangle: (CWDI = square root of CD2 + WD2). Perinatal outcomes were evaluated by the number of perinatal deaths, delivery for fetal indications prior to 37 weeks' gestation, five-minute Apgar score < 7, neonatal intensive care unit (NICU) admission and the presence of intrauterine growth retardation (IUGR). A CWDI value of > or = 20 was the most discriminatory in identifying fetuses with poor outcomes. Fetuses with CWDI > or = 20 were more likely to be premature (P < .001) or growth retarded (P < .001) or have lower Apgar scores (P < .005) and longer NICU stays (P < .001). Seven of the eight perinatal deaths occurred in patients with abnormal CWDI (P < .001). The sensitivity of an abnormal CWDI was 95% for IUGR, 60% for preterm delivery, 82% for NICU admission, 90% for Apgar score < 7 at five minutes, 87% for perinatal mortality and 68% for overall poor perinatal outcomes. CWDI is a sensitive index for the identification of fetuses with IUGR and poor perinatal outcome. PMID- 7996524 TI - Hyperemesis gravidarum. A review. AB - Hyperemesis gravidarum is a common entity the cause of which has remained poorly defined. However, it probably is a classic example of the interplay between biologic, psychological and sociological variables. Current data on hyperemesis gravidarum and the pertinent literature for the last two decades are reviewed. PMID- 7996525 TI - Tocolysis for recurrent preterm labor using a continuous subcutaneous infusion pump. AB - This study attempted to determine the best method of treatment for patients with recurrent preterm labor: administration of terbutaline via an automated, programmable, subcutaneous infusion pump or oral terbutaline. In this retrospective, controlled study, 32 patients diagnosed with recurrent preterm labor, as determined by persistent uterine contractions with cervical change, were treated with a programmable infusion pump adjusted to control uterine contraction frequency to < or = 4 contractions per hour. Patients in this group were matched for age, race, parity, gestational age and cervical dilation at diagnosis of recurrent preterm labor in subjects taking oral terbutaline. The patients receiving oral terbutaline were given an average of 6.5 mg every four to six hours to maintain uterine quiescence, while those in the pump group were given basal rates of terbutaline and in addition received four to six boluses per day (< 3 mg/d total dose) to achieve this outcome. Patients using the pump were more likely to reach term and less likely to fail tocolytic therapy than were those taking oral terbutaline. The terbutaline pump appeared to be more successful in prolonging pregnancies to term after the diagnosis of recurrent preterm labor than did oral terbutaline. PMID- 7996526 TI - Use of the Edinburgh Postnatal Depression Scale to identify postpartum depression in a clinical setting. AB - The Edinburgh Postnatal Depression Scale (EPDS) is a validated instrument developed specifically to identify women experiencing postpartum depression (PPD). This study sought to determine the extent of postpartum depression in our population and the maternal characteristics associated with it and to also determine if the scale increased practitioner awareness and treatment of PPD. Two hundred eighty-seven women from the total population completing the EPDS in 1991 (n = 1,139) were randomly selected for retrospective chart review to identify relationships between maternal characteristics and elevated EPDS scores. Charts were also reviewed for outcomes related to depression for the six-month period after delivery. Statistical analysis of the data revealed that 17.4% of the total population had an EPDS score of > or = 10, indicating a potential risk of developing PPD. Eight percent scored > or = 13, suggesting that further assessment was necessary. Marital instability, lack of medical insurance and a history of depression were the factors found to correlate most significantly with elevated EPDS scores. The physicians and midwives providing service for our population were interviewed, and 83% reported that the EPDS had increased their awareness of PPD, while 92% reported having referred for treatment patients with high EPDS scores. Use of the EPDS scale can improve practitioner awareness and aid in the diagnosis of PPD. Several easily identifiable variables are associated with PPD. PMID- 7996527 TI - Laparoscopic hysterectomy. Supracervical vs. assisted vaginal. AB - Twenty cases of laparoscopic supracervical hysterectomy performed by operative laparoscopy without vaginal assistance were retrospectively compared to 232 cases of laparoscopically assisted vaginal hysterectomy reported in the literature. The specimens were morcellated intraabdominally and removed through the umbilicus. This is the first reported series of this technique with intraabdominal morcellation, which emphasizes cosmetic considerations and remains within the confines of the umbilicus. The postoperative hospitalization time ranged from 3.75 to 22.2 hours. On the second postoperative day, 10% of the patients returned to work, and 15% were able to drive. Patients resumed normal activity in an average of 5.6 days after surgery. As compared to laparoscopically assisted vaginal hysterectomy, there was a decrease in morbidity, blood loss and recovery time. Prolonged anesthesia from the longer operating time was clinically insignificant in terms of the patients' recovery. By decreasing the disability from hysterectomy from six weeks to one, the procedure provided financial savings through work time gained. PMID- 7996528 TI - Formal resident training in urogynecology and pelvic floor disorders. A six-year survey. AB - An observational study reviewed the efficacy of resident training in urogynecology and pelvic floor disorders. After instituting a formal urogynecology rotation consisting of two one-month rotations in the second and third years at a major inner city county hospital, 24 residents were prospectively followed to assess their cognitive and clinical skills, including endoscopic, urodynamic and surgical competence. They were evaluated by objective testing and close observation. The results showed 41.875% (+/- 16.669 SD) entry level objective correct answers as compared to 82.083% (+/- 10.206) upon completion of the rotation. Residents were observed and graded over the six-year period by one (occasionally two) faculty members for successful task completion. The residents' mastery of surgical, endoscopic and urodynamic skills was deemed acceptable through a subjective evaluation by urogynecology faculty members based on satisfactory completion of 80% of the assigned task. Formal urogynecologic training by a knowledgeable subspecialist is a useful adjunct to the obstetrics and-gynecology residency program. PMID- 7996529 TI - Resident research in obstetrics and gynecology. AB - Mandatory research in an obstetrics-and-gynecology residency can be an effective tool for teaching physicians the skills needed for them to become intelligent readers of the medical literature. We present our 15-year experience with a resident research program. We discovered that in addition to achieving the primary goal in resident education, structured resident research has many other benefits. PMID- 7996531 TI - Congenital hypopituitarism as part of suprasellar dysplasia. A case report. AB - Congenital hypopituitarism may be due to hypothalamic failure. The case presented below belonged to this category. In addition, the demonstration of absent septum pellucidum placed this case in the category of suprasellar dysplasia. The patient was 21 years old, with primary amenorrhea and lack of development of secondary sex characteristics. The laboratory findings confirmed the diagnosis of hypothyroidism, hypocortisolism, hypogonadotropism, hyperprolactinemia and normal growth hormone. Stimulation studies revealed a subnormal response of cortisol to adrenocorticotrophic hormone stimulation, subnormal response of follicle stimulating hormone and luteinizing hormone to gonadotropin releasing hormone stimulation, normal response of prolactin to thyrotropin releasing hormone stimulation and exaggerated response of thyroid stimulating hormone to thyrotropin releasing hormone stimulation. The patient was treated with thyroid supplementation. Magnetic resonance imaging showed a hypoplastic infundibulum, ectopic neurohypophysis, small anterior pituitary gland and absent septum pellucidum. Congenital hypopituitarism may be part of a large spectrum of midline brain abnormalities. PMID- 7996530 TI - Complex hyperplasia of the endometrium. Predictive value of curettage vs. hysterectomy specimens. AB - We reviewed 94 cases of complex endometrial hyperplasia (CH) with and without atypia to assess some of the clinical and pathologic changes observed on curettage and in hysterectomy specimens. Age, parity, height, weight and nomograms did not differ between CH with or without atypia, and CH associated with endometrial carcinoma. CH without atypia, however, predicted lesser degrees of malignancy as compared to CH with atypia. Progesterone or progestinlike treatment is indicated for CH without atypia along with endometrial monitoring, but CH with atypia necessitates diagnostic and therapeutic hysterectomy whenever fertility is not a priority. PMID- 7996532 TI - Streptococcal toxic shock-like syndrome as an unusual complication of laparoscopic tubal ligation. A case report. AB - Toxic shock-like syndrome due to Streptococcus pyogenes is an unusual occurrence. Previously reported cases have been the result of focal infections with S pyogenes. We present a case in which manipulation of a colonized mucosal surface during laparoscopic tubal ligation was the presumed cause of the sepsis syndrome. Whereas other reports of this syndrome have all noted concurrent infections with S pyogenes, in this instance it was unclear if toxin-mediated disease was initiated by mild endometritis or iatrogenic manipulation of a colonized mucosal surface. PMID- 7996533 TI - Leiomyomatosis peritonealis disseminata. A report of two cases. AB - Leiomyomatosis peritonealis disseminata (LPD), also known as diffuse peritoneal leiomyomatosis, is characterized by the presence of multiple, small nodules scattered over the abdominopelvic viscera and peritoneum. These nodules are composed of benign smooth muscle cells. As shown in this report of two cases, the disorder occurs mostly in women of reproductive age and rarely in postmenopausal ones. LPD is a benign condition for which conservative management is indicated. PMID- 7996534 TI - Neonatal depression after a protamine sulfate injection. A case report. AB - The intravenous administration of protamine sulfate in adults has been associated with acute hypotension, bradycardia and anaphylactoid reactions. However, no reports of its use in pregnancy have been available before. We describe a case of severe neonatal depression following maternal protamine sulfate injection immediately prior to delivery. PMID- 7996535 TI - Lactation from axillary breast tissue in the absence of a supernumerary nipple. A case report. AB - A case of lactation apparently from axillary supernumerary breast tissue was observed in a lactating woman. The tissue showed histologic features typical of both normal glands of lactation and apocrine sweat glands, and the fluid showed evidence of milk production. The supernumerary breast tissue was not associated with a nipple. Renal and skeletal anomalies were also noted. PMID- 7996536 TI - Use of a gonadotropin releasing hormone agonist before vaginal surgery for cervical leiomyomas. A report of two cases. AB - Two cases of cervical myoma were treated with combined medical/surgical therapy using a gonadotropin releasing hormone agonist (GnRH-a) and transvaginal cervical myomectomy. Patients were treated with depot GnRH-a (leuprolide acetate) for two months followed by myomectomy. This approach allowed successful treatment with short hospitalization (< 24 hours). Potential benefits of this regimen include decreased intraoperative blood loss, outpatient management, decreased morbidity, decreased hospital expense and preservation of reproductive potential by avoiding hysterectomy. PMID- 7996537 TI - Novel zinc chelators which inhibit the binding of HIV-EP1 (HIV enhancer binding protein) to NF-kappa B recognition sequence. PMID- 7996539 TI - Cholinergic agents structurally related to furtrethonium. 2. Synthesis and antimuscarinic activity of a series of N-[5-[(1'-substituted-acetoxy) methyl]-2 furfuryl]dialkylamines. AB - In the first part of this study, devoted to the discovery of selective antimuscarinic agents, (+/-)- N-[5-[(1'-phenyl-1'-cyclohexylacetoxy)methyl]-2 furfuryl]dimeth yla mine (5a) proved to be at least 20 times more potent in the rat ileum and bladder than in guinea pig atria. Several (+/-)-N- [5-[(1' substituted-acetoxy)methyl]-2-furfuryl]dialkylamine analogs of 5a were subsequently prepared. This involved exploration of the tertiary nitrogen substituents and modulation of the lipophilic side chain at position 5 of the furan ring, using the Hansch approach. A QSAR study was conducted to correlate activity with physicochemical properties of substituents. The possibility of describing all compounds in a single model indicates that variations of nitrogen and the lipophilic side chain contribute independently to activity. Compounds 5b, c,j, with bulky lipophilic substituents at the tertiary nitrogen, showed unprecedented selectivity between the two smooth muscle tissues, their antimuscarinic potency being from 10 to 90 times higher in the ileum than in the bladder. It is suggested that their interesting tissue selectivity is probably related to nonspecific phenomena involving the receptor environment, rather than real differences between the muscarinic receptors in the two tissues. PMID- 7996538 TI - Synthesis and opioid receptor affinity of a series of aralkyl ethers of 6 alpha- and 6 beta-naltrexol. AB - A series of 6-O-ethers of 6 beta- and 6 alpha-naltrexol (6 and 7) were prepared to examine the effect of large aralkyl groups on affinity of the ligands for opioid receptors. The affinities of the 6 beta- and 6 alpha-O-ether with benzyl, biphenylmethyl, 1- and 2-naphthylmethyl, and 9-anthracylmethyl groups were determined. Preparation of the ligands was accomplished from suitably 3-O protected derivatives of 6 and 7 by phase transfer catalyzed alkylation using aralkyl halides, followed by deprotection. Both 3-O-trityl and -benzyl protecting groups were used. In radioligand displacement assays, compounds from the 6 alpha O ether series had higher affinity than the analogous diastereomers in the 6 beta O series, with few exceptions. In the 6 alpha-O series, the benzyl ether (29) and the biphenylmethyl ether (30) had the highest affinity, similar to naltrexone. In the 6 beta-O series, the benzyl ether had the highest affinity. The larger aralkyl ethers had slightly less affinity. Large lipophilic 6 beta-O- and 6 alpha O-aralkyl groups are readily accommodated in the drug-receptor interaction. PMID- 7996540 TI - Synthesis, NMDA receptor antagonist activity, and anticonvulsant action of 1 aminocyclobutanecarboxylic acid derivatives. AB - A range of cis- and trans-3-substituted 1-aminocyclobutane-1-carboxylic acids has been synthesized and evaluated for antagonism at excitatory amino acid receptor sites and for anticonvulsant activity. Potent and selective antagonist activity at N-methyl-D-aspartate (NMDA) receptor sites in neonatal rat motoneurones was shown by compounds in which the 3-substituent was, or contained, a 2' carboxyethyl or 2'-phosphonoethyl moiety. Substances 4b, 24, 35, and 40 were more potent than the standard NMDA receptor antagonist, D-2-amino-5 phosphonopentanoate (D-AP5) as NMDA antagonists in this preparation, and about equipotent with [3-(+/-)-2-carboxypiperazin-4-yl)-1-propyl]phosphonate (CPP). Anticonvulsant activity, as assessed following intracerebroventricular injection into audiogenic DBA/2 mice, generally paralleled NMDA receptor antagonist activity. PMID- 7996541 TI - Synthesis, in vitro biological stability, and anti-HIV activity of 5-halo-6 alkoxy(or azido)-5,6-dihydro-3'-azido-3'-deoxythymidine diastereomers as potential prodrugs to 3'-azido-3'-deoxythymidine (AZT). AB - A new class of 5-halo-6-alkoxy(or azido)-5,6-dihydro-3'-azido-3'-deoxythymidines was investigated as potential anti-AIDS drugs. These 5,6-dihydro derivatives, which are also potential prodrugs to 3'-azido-3'-deoxythymidine (AZT), were designed in an effort to enhance the duration of action, lipophilicity, and cephalic delivery to the central nervous system. The 5-halo-6-alkoxy(or azido) 5,6-dihydro-3'-azido-3'-deoxythymidines, which differ in configuration at the C-5 and C-6 positions, were synthesized by the regiospecific addition of XR (X = Br, Cl, I; R = alkoxy, azido) to the 5,6-olefinic bond of AZT. The 5-halo-6-methoxy 5,6-dihydro derivatives of AZT are more lipophilic (P = 3.3-18.8 range) than the parent compound AZT (P = 1.29). These 5-halo-6-methoxy-5,6-dihydro compounds, like AZT, did not undergo glycosidic bond cleavage upon incubation with Escherichia coli thymidine phosphorylase. Regeneration of the 5,6-olefinic bond to give AZT, upon incubation of the 5-halo-6-methoxy-5,6-dihydro compounds with glutathione, mouse blood, or mouse liver homogenate, was dependent upon the nature of the 5-halo substituent (I > Br). No 5,6-olefinic bond regeneration was observed for the 5-chloro analogs. The ability of these 5-halo-6-alkoxy (or azido)-5,6-dihydro-3'-azido-3'-deoxythymidines to protect CEM cells against HIV induced cytopathogenicity was evaluated. Structure-activity studies showed that the C-5 substituent (I, Br, Cl) was a determinant of anti-HIV-1 activity where the potency order was I > or = Br > Cl. In the 5-bromo series of compounds, the C 6 substituent was also a determinant of activity where 6-OMe and 6-OEt substituents exhibited a greater potency than the corresponding 6-i-PrO, 6-(1 octyloxy), 6-(1-hexadecyloxy), and 6-azido analogs. All of the 5-chloro-6 substituted-5,6-dihydro compounds were inactive, except for the approximately equipotent 6-OMe and 6-azido diastereomeric mixtures which were 2-3 log units less active than the reference drug AZT. The configuration at the C-5 and C-6 positions also influenced potency where the activity of the 5R,6R-diastereomer was generally greater than that of the corresponding 5S,6S-diastereomer.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 7996542 TI - N6-substituted adenosine receptor agonists. Synthesis and pharmacological activity as potent antinociceptive agents. AB - Novel N6-(indol-3-yl)alkyl derivatives of adenosine were synthesized. The adenosine receptor affinity and the antinociceptive activity of these compounds were assessed in binding studies and the phenylbenzoquinone-induced writhing test. Most of these analogues exhibited a potent analgesic activity without side effects. Among them, compound 3c (UP 202-32) bound to A1 (Ki = 110 nM) and A2 (Ki = 350 nM) adenosine receptors in a specific manner since it did not interact with many other receptors, especially opioid binding sites. The antinociceptive activity in the phenylbenzoquinone assay (ED50 = 3.3 mg/kg po) was antagonized by 8-cyclopentyltheophylline, suggesting that an adenosinergic mechanism underlies the analgesic activity observed with this compound. The data obtained with these new N6-substituted adenosine receptor agonists emphasize the interest of such compounds in the treatment of pain. PMID- 7996543 TI - Synthesis and molecular modeling of 1-phenyl-1,2,3,4-tetrahydroisoquinolines and related 5,6,8,9-tetrahydro-13bH-dibenzo[a,h]quinolizines as D1 dopamine antagonists. AB - New 1-phenyl-1,2,3,4-tetrahydroisoquinolines and related 5,6,8,9-tetrahydro- 13bH dibenzo[a,h]-quinolizines were prepared as ring-contracted analogs of the prototypical 1-phenyl-2,3,4,5-tetrahydrobenzazepines (e.g., SCH23390) as a continuation of our studies to characterize the antagonist binding pharmacophore of the D1 dopamine receptor. Receptor affinity was assessed by competition for [3H]SCH23390 binding sites in rat striatal membranes. The 6-bromo-1 phenyltetrahydroisoquinoline analog 2 of SCH23390 1 had D1 binding affinity similar to that for the previously reported 6-chloro analog 6, whereas the 6,7 dihydroxy analog 5 had significantly lower D1 affinity. Conversely, neither 6 monohydroxy- (3) nor 7-monohydroxy-1-phenyltetrahydroisoquinolines (4) had significant affinity for the D1 receptor. These results demonstrate that 6-halo and 7-hydroxy substituents influence D1 binding affinity of the 1 phenyltetrahydroisoquinolines in a fashion similar to their effects on 1 phenyltetrahydrobenzazepines. The conformationally constrained 3-chloro-2 hydroxytetrahydrodibenzoquinolizine 9 had much lower affinity relative to the corresponding, and more flexible, 6-chloro-7-hydroxy-1 phenyltetrahydroisoquinoline 6. Similarly, 2,3 dihydroxytetrahydrodibenzoquinolizine 10 had much lower D1 affinity compared to dihydrexidine 14, a structurally similar hexahydrobenzo[a]phenanthridine that is a high-affinity full D1 agonist. Together, these data not only confirm the effects of the halo and hydroxy substitutents on the parent nucleus but demonstrate the pharmacophoric importance of both the nitrogen position and the orientation of the accessory phenyl ring in modulating D1 receptor affinity and function. Molecular modeling studies and conformational analyses were conducted using the data from these new analogs in combination with the data from compounds previously synthesized. The resulting geometries were used to refine a working model of the D1 antagonist pharmacophore using conventional quantitative structure-activity relationships and three-dimensional QSAR (CoMFA). PMID- 7996544 TI - Synthesis and antitumor activity of a new class of pyrazolo[4,3-e]pyrrolo[1,2 a][1,4]diazepinone analogues of pyrrolo[1,4][2,1-c]benzodiazepines. AB - A new class of pyrrolo[1,4]benzodiazepine (PBD) analogues featuring a pyrazolo[4,3-e]pyrrolo[1,2-a][1,4]diazepinone ring system has been designed and synthesized. These compounds, 2a-o, are characterized by the substitution of the aromatic A ring, characteristic of the PBDs, with a disubstituted pyrazole ring bearing alkyl and benzyl substituents at N6 or N7 and alkyl or carbomethoxy substituents at C8. Biological evaluation revealed an appreciable in vitro cytotoxic activity for compounds 2a,b,f-i. PMID- 7996546 TI - Bioreductive markers for hypoxic cells: 2-nitroimidazoles with biotinylated 1 substituents. AB - The interference by oxygen with the bioreductive metabolism and binding within cells of 2-nitroimidazoles has been used to identify hypoxic cells. Three novel compounds were synthesized with a 1-substituent containing a biotin moiety. Bound adducts of these compounds could be identified in hypoxic cells in vitro by the biotin binding proteins, avidin or streptavidin, labeled with fluorescein. The metabolism and discrimination of these compounds between well-oxygenated and hypoxic cells was evaluated by flow cytometry. Ester or amide links between the 2 nitroimidazole and the biotin were degraded in the presence of mouse serum, but a compound with a C5 hydrocarbon link was stable, and this compound was suitable for evaluation in an in vivo tumor model. PMID- 7996545 TI - 1-(2,5-Dimethoxy-4-(trifluoromethyl)phenyl)-2-aminopropane: a potent serotonin 5 HT2A/2C agonist. AB - A method was found to synthesize 1-(2,5-dimethoxy-4-(trifluoromethyl) phenyl)-2 aminopropane, 5, and its des-alpha-methyl congener 2-(2,5-dimethoxy-4 (trifluoromethyl)phenyl)aminoethane, 6, the trifluoromethyl analogs of substituted hallucinogenic phenethylamine derivatives such as 1-(2,5-dimethoxy-4 iodophenyl)-2-aminopropane (3, DOI) that are potent 5-HT2A/2C agonists. In our hands, 5 and 6 have proven to have affinity for [3H]ketanserin or [125I]-3 labeled 5-HT2A/2C sites in rat cortex comparable to or higher than the analogous bromo or iodo analogs. Similarly, 5 and 6 had potency comparable to or slightly greater than that of their bromo or iodo congeners in the two-lever drug discrimination assay in rats trained to discriminate saline from LSD tartrate. The agonist properties of 5 and 6 were evaluated by measuring the accumulation of [3H]inositol monophosphate in cultured cells selectively expressing either 5-HT2A or 5-HT2C receptors. In comparison to serotonin (5-HT), compounds 3 (DOI), 5, and 6 were equally efficacious and full agonists at the 5-HT2C receptor. Similarly, 3 and 5 produced equivalent responses at the 5-HT2A receptor as compared to 5-HT. In contrast, 6, the alpha-desmethyl analog of 5, was only half as potent at stimulating inositol monophosphate accumulation at the 5-HT2A receptor. In conclusion, the title compound 5 and its alpha-desmethyl congener 6 appear to be the most potent of the so-called hallucinogenic amphetamine 5-HT agonists reported to date. Further, the reduced efficacy of 6 at the 5-HT2A receptor may offer at least a partial explanation for the observed higher in vivo potencies of alpha-methyl-substituted compounds in this series. PMID- 7996547 TI - Inhibition of myeloperoxidase release from rat polymorphonuclear leukocytes by a series of azachalcone derivatives. AB - A series of azachalcones was evaluated for ability to affect secretion of myeloperoxidase by rat polymorphonuclear leukocytes stimulated by fMLP. The compounds were found to interfere with cellular uptake of extracellular calcium. Structure-activity relationships are discussed. PMID- 7996548 TI - Mobilization of iron by chiral and achiral anionic 3-hydroxypyrid-4-ones. AB - In the search for 3-hydroxypyrid-4-ones with enhanced iron-mobilizing ability, seven chiral, anionic amino acid derivatives of maltol (3-hydroxy-2-methyl-4 pyrone) have been synthesized, utilizing L-methionine, L-serine, L-leucine, L phenylalanine, L-glutamic acid, and the D- and L-isomers of alanine. Two achiral, aromatic compounds were also synthesized and compared with the phenylalanine derivative. The biliary iron excretion following iv injection and the urinary iron excretion following po administration were measured using female Sprague Dawley rats and compared to that of the standard, 1,2-dimethyl-3-hydroxypyrid-4 one (L1). While none of the compounds was as effective as L1 in enhancing the urinary excretion of iron, all monoanionic chelators increased excretion relative to the controls. All monoanionic compounds were at least equivalent to L1 in enhancing the biliary excretion of iron, with the methionine, leucine, and benzoate derivatives surpassing the standard and the other aromatic compounds also showing strong activity. The dianionic glutamate derivative showed low activity relative to the controls for both urinary and biliary iron excretion. No significant difference in iron excretion was observed due to variation in chirality; molecular weight and the number of negative charges appeared to have the greatest influence on the ability of the various derivatives to enhance iron excretion. In order to evaluate the relative purity of the stereoisomers, the alanine derivatives were analyzed by circular dichroism. Further characterization was provided by UV/vis spectroscopy for all compounds and X-ray crystallography for the novel dianionic derivative. PMID- 7996549 TI - Development of a model for the delta opioid receptor pharmacophore. 1. Conformationally restricted Tyr1 replacements in the cyclic delta receptor selective tetrapeptide Tyr-c[D-Cys-Phe-D-Pen]OH (JOM-13). AB - A series of analogues of the conformationally restricted delta opioid receptor selective tetrapeptide Tyr-c[D-Cys-Phe-D-Pen]OH (JOM 13) was prepared in which the conformationally labile Tyr residue was replaced with several less flexible tyrosine analogues. Among these tyrosine analogues were the bicyclic structures 1,2,3,4-tetrahydro-7-hydroxyisoquinoline-3-carboxylic acid (HO-Tic), 2-amino-6 hydroxytetralin-2-carboxylic acid (Hat), and 2-amino-5-hydroxyindan-2-carboxylic acid (Hai) in which rotations about the C alpha-C beta and C beta-C gamma bonds are restricted due to cyclization of the side chain to the backbone. Also examined were analogues in which tyrosine was replaced with either trans-3-(4' hydroxyphenyl)proline (t-Hpp) or cis-3-(4'-hydroxyphenyl)proline (c-Hpp), residues in which rotations about C alpha-C beta, but not C beta-C gamma, are restricted. Both the t-Hpp1 and c-Hpp1 analogues displayed delta receptor binding affinity similar to the parent Tyr1-containing peptide, while the D-Hat1, L-Hat1, and L-Hai1 analogues exhibited somewhat lower affinity. The results observed for the t-Hpp1 and c-Hpp1 analogues are particularly significant since these two residues have little accessible conformational space in common. Since the binding conformation of residue 1 must be included in this limited conformational intersection, its elucidation is facilitated. Bioassay results from guinea pig ileum and mouse vas deferens preparations are in general agreement with the binding results; however some potency discrepancies are observed. These discrepancies may reflect different selectivities among delta receptor subtypes for the analogues or may represent differing efficacies among these conformationally restricted peptides. The conformational properties of the parent tetrapeptide and the residue 1-modified analogues were studied by molecular mechanics computations. All these peptides share a common rigid tripeptide cycle with a single energetically preferred backbone conformation and three different conformers of the D-Cys, D-Pen disulfide bridge, two of which are observed in the solid state and in aqueous solution, as previously determined from X-ray crystallography and 1H NMR spectroscopy data (Lomize, A; et al. J. Am. Chem. Soc. 1994, 116, 429-436). All the peptides have similar sets of low-energy conformations of their common flexible elements, the Phe3 side chain and the peptide group between the first residue and the rigid tripeptide cycle. However, possible conformations of the first residue differ and depend on the covalent constraints incorporated into the side chain.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 7996550 TI - Development of a model for the delta opioid receptor pharmacophore. 2. Conformationally restricted Phe3 replacements in the cyclic delta receptor selective tetrapeptide Tyr-c[D-Cys-Phe-D-Pen]OH (JOM-13). AB - The in vitro pharmacological properties and conformational features of analogs of the delta opioid receptor selective tetrapeptide Tyr-c[D-Cys-Phe-D-Pen]OH (JOM 13) in which the Phe3 residue was replaced by each of the four stereoisomers of beta-methylphenylalanine (beta-MePhe) were investigated. Both analogs in which the alpha carbon of the Phe3 replacement has L-stereochemistry display high affinity for delta receptors with the (2S,3S)-MePhe3 analog exhibiting approximately 8-fold higher affinity than the (2S,3R)-MePhe3 diastereomer. Surprisingly, one analog with D-stereochemistry in residue 3, the (2R,3R)-MePhe3 analog, also displays high affinity for the delta receptor and is extraordinarily selective for this receptor. All analogs were agonists in the mouse vas deferens (MVD) and guinea pig ileum (GPI) smooth muscle bioassays, displaying MVD and GPI potencies consistent with their delta and mu opioid receptor affinities, respectively. The use of beta-MePhe as a replacement for Phe3 was based upon the desire to reduce the conformational flexibility of the Phe3 side chain by imposing a steric rotational constraint in the form of the beta-methyl substituent and to thus deduce the residue 3 side chain orientation in the delta receptor-bound conformation from the correlation between delta receptor binding affinities and conformational preferences. Molecular mechanics computations revealed, however, that the conformational constraints imposed by the beta-methyl group in the (2S,3S)-MePhe3 and (2S,3R)-MePhe3 analogs were too modest to allow unequivocal determination of delta receptor-bound residue 3 side chain conformation. However, analysis of the high-affinity (2R,3R)-MePhe3 analog revealed a strong preference for a single side chain conformer (chi 1 approximately 60 degrees). Low-energy conformers of this analog could only be effectively superimposed with low-energy conformers of the parent peptide in which the Phe3 side chain conformation was limited to chi 1 approximately -60 degrees. This observation eliminates the last remaining uncertainty regarding conformational features of the pharmacophore elements in the delta receptor-bound state, allowing the proposal of a complete model. PMID- 7996551 TI - Interaction of calcium channel antagonists with calcium: structural studies on nicardipine and its Ca2+ complex. AB - Conformational features of nicardipine in acetonitrile, in the absence and presence of Ca2+, were investigated by one-dimensional NMR and difference absorption spectroscopy techniques. The data show that in acetonitrile solution the antiperiplanar form of nicardipine is dominant. The addition of Ca2+ to the drug solution caused marked changes in the difference absorbance spectra in the 200-400 nm region and in many of its 1H and 13C NMR resonances. The changes were most significant up to a ratio of 0.5 Ca2+:drug. Analysis of the binding data showed the predominant species to be a 2:1 drug:Ca2+ "sandwich" complex with an estimated dissociation constant of 100 microM at 25 degrees C. One-dimensional nuclear Overhauser effect (NOE) experiments revealed through-space connectivities in the drug before and after Ca2+ binding. These changes in conjunction with the changes in 1H and 13C chemical shifts suggest a structure in which the 4-aryl ring substitute of the pyridine moiety moves closer to the C3-side chain in the presence of Ca2+. This attraction is achieved via the chelation of the Ca2+ ion by the oxygen atoms in the m-NO2 of the aryl group and the COOCH2 group in the side chain of the dihydropyridine ring, and gives rise to a stable synperiplanar conformation. A preference for this conformation was also observed in the Ca2+ complex of nifedipine in acetonitrile as inferred from the rather limited NOE data obtained. Our study provides a detailed solution structure for nicardipine and also leads to a suggestion of a role for Ca2+ in the action of this and possibly other dihydropyridines. PMID- 7996552 TI - Structure-distribution relationships for metal-labeled myocardial imaging agents: comparison of a series of cationic gallium (III) complexes with hexadentate bis(salicylaldimine) ligands. AB - A series of 10 cationic gallium(III) complexes with hexadentate bis(salicylaldimine) ligands were synthesized, characterized, radiolabeled with 67Ga, and screened in a rat model to assess their potential as 68Ga radiopharmaceuticals for imaging the heart with positron emission tomography. The tris(salicylaldimine) ligand precursors were synthesized by condensation of either bis(3-aminopropyl)ethylenediamine (BAPEN) or bis(2,2-dimethyl-3 aminopropyl)ethylenediamine (DM-BAPEN) with 3 equiv of a salicylaldehyde derivative containing alkyl, alkoxy, or alkylamino substituents in the 4, 5, or 6 position of the aromatic ring. The cationic six-coordinate gallium(III) bis(salicylaldimine) complexes were obtained by reaction of these tris(salicylaldimines) with tris(acetylacetonato)gallium(III). X-ray crystallographic confirmation of the molecular structure of Ga[(4,6-(MeO)2sal)2DM BAPEN]+I- shows the Ga cation to adopt a pseudo-octahedral N4O2 coordination sphere with a trans configuration. All of the 67Ga complexes are lipophilic with measured octanol/water partition coefficients (P) varying from log P = 0.84 to 3.00. These 67Ga-labeled complexes are all found to exhibit significant myocardial uptake following intravenous administration to rats (ranging from 0.34 to 1.08% of the injected dose in myocardium at 1 min postinjection) combined with the desired myocardial retention of tracer. PMID- 7996553 TI - Isolation and structure/activity features of halomon-related antitumor monoterpenes from the red alga Portieria hornemannii. AB - Ten halogenated monoterpenes (2-6 and 8-12) related to the novel antitumor compound halomon (1) or to the carbocyclic analog 7 have been isolated from different geographic collections of the red alga, Portieria hornemannii. Structures were assigned to the basis of spectral analyses (primarily NMR and MS). The absolute configuration of isohalomon (2) was further established by X ray crystallography. The compounds were comparatively evaluated alongside 1 and 7 in the U.S. National Cancer Institute's in vitro human tumor cell line screening panel. The results provide some interesting initial insights into the structure/activity relationships in this series. PMID- 7996554 TI - Furoxans as nitric oxide donors. 4-Phenyl-3-furoxancarbonitrile: thiol-mediated nitric oxide release and biological evaluation. AB - 4-Phenyl-3-furoxancarbonitrile (2) affords nitric oxide under the action of thiol cofactors. Two principal products were isolated in the reaction with thiophenol: the phenylcyanoglyoxime (6) and 5-amino-3-phenyl-4-(phenylthio)isoxazole (7). Mechanisms which could account for the formation of these two products are discussed. Compound 2 is an efficient activator of the rat lung soluble guanylate cyclase, displays high vasodilatory activity on strips of rat thoracic aorta precontracted with noradrenaline, and is a potent inhibitor of platelet aggregation. PMID- 7996555 TI - Bis-catechol-substituted redox-reactive analogues of hexamethonium and decamethonium: stimulated affinity-dependent reactivity through iron peroxide catalysis. AB - Symmetrically bis-catechol-substituted analogues (1 and 2, respectively) of hexamethonium and decamethonium were synthesized and investigated as redox activated affinity reagents toward the neurotoxin-binding sites of the nicotinic acetylcholine receptor (nAcChR), purified from Torpedo californica electroplax. These reagents bound to nAcChR with Kd = 1.8 x 10(-8) and 2.3 x 10(-7) M for 1 and 2, respectively. In the presence of a metal, Fe(II)/Fe(III), and peroxide, both reagents produced a rapid and efficient half-of-sites inactivation of neurotoxin-binding sites in the nAcChR in a concentration-dependent manner, which paralleled the extent of receptor binding of the reagents. In the absence of Fe(II)/Fe(III) peroxide, redox-dependent inactivation occurred for both 1 and 2 more slowly and only at concentrations much higher (10(3)-10(4) times) than those necessary to produce significant binding to nAcChR. However, receptor inactivation in the absence of added metal peroxide was still more efficient for 1 and 2 than observed previously for [(trimethylammonio)methyl]catechol (3), the prototypic redox-dependent affinity reagent after which 1 and 2 were patterned. Thus, the new reagents reported are expected to provide more efficient and selective conditions for redox-dependent inactivation at nAcChR and other macromolecular sites to which such reagents may be directed. PMID- 7996556 TI - Palliative care ethics: non-provision of artificial nutrition and hydration to terminally ill sedated patients. PMID- 7996557 TI - Christian ethics--an irrelevance or the salvation of medicine? PMID- 7996558 TI - Psychiatric diagnosis, psychiatric power and psychiatric abuse. AB - Psychiatric abuse, such as we usually associate with practices in the former Soviet Union, is related not to the misuse of psychiatric diagnoses, but to the political power intrinsic to the social role of the psychiatrist in totalitarian and democratic societies alike. Some reflections are offered on the modern, therapeutic state's proclivity to treat adults as patients rather than citizens, disjoin rights from responsibilities, and thus corrupt the language of political philosophical discourse. PMID- 7996559 TI - First trimester prenatal diagnosis: earlier is not necessarily better. AB - In the past few years considerable attention has been given to a relatively new method of prenatal diagnosis known as chorionic villus sampling (CVS). Because CVS can be performed in the first trimester it is hailed by many as a significant advance over amniocentesis. What has not been as publicized, however, are the disadvantages of CVS and earlier prenatal diagnosis. The emotional costs of CVS in terms of the greater number of both spontaneous and selective abortions following CVS, the use of CVS for sex selection and, because of the greater social acceptability of first trimester abortion, the possibility of increased pressure on women to undergo prenatal diagnosis by health insurance companies, medical professionals and government agencies, all need to be weighed against the advantages of early prenatal diagnosis. PMID- 7996560 TI - Enhancing patient well-being: advocacy or negotiation? AB - The United Kingdom Central Council for Nursing, Midwifery and Health Visitors (UKCC) document, Exercising Accountability, states that the role of patient's advocate is an essential aspect of good professional nursing practice (1). The author examines the case for and against the nurse being the best person to act as advocate, and critically evaluates the criteria of advocacy. The problematic moral issues arising are discussed, and a case made for negotiation between the members of the multidisciplinary team and the patient/client (or a significant person to the patient) in order to promote the well-being of the patient and to minimise suffering. She concludes that the health care professional's (including the nurse's) role is to help people to assert control over the factors which affect their lives, that is empowerment, rather than advocacy. PMID- 7996561 TI - Distinguishing genetics and eugenics on the basis of fairness. AB - There is concern that human applications of modern genetic technologies may lead inexorably to eugenic abuse. To prevent such abuse, it is essential to have clear, formal principles as well as algorithms for distinguishing genetics from eugenics. This work identifies essential distinctions between eugenics and genetics in the implied nature of the social contract and the importance ascribed to individual welfare relative to society. Rawls's construction of 'justice as fairness' is used as a model for how a formal systems of ethics can be used to proscribe eugenic practices. Rawls's synthesis can be applied to this problem if it is assumed that in the original condition all individuals are ignorant of their genetic constitution and unwilling to consent to social structures which may constrain their own potential. The principles of fairness applied to genetics requires that genetic interventions be directed at extending individual liberties and be applied to the greatest benefit of individuals with the least advantages. These principles are incompatible with negative eugenics which would further penalize those with genetic disadvantage. These principles limit positive eugenics to those practices which are designed to provide absolute benefit to those individuals with least advantage, are acceptable to its subjects, and further a system of basic equal liberties. This analysis also illustrates how simple deviations from first principles in Rawls's formulation could countenance eugenic applications of genetic technologies. PMID- 7996562 TI - Minimal breaches of confidentiality in health care research: a Canadian perspective. AB - In a large proportion of health care research based on the retrospective review of records, minimal breach of patient confidentiality appears to be inevitable. This occurs at initial identification of and access to the chart, selected on the basis of the condition under investigation, and while individual identifiability can be blocked at subsequent stages, at this point it does occur. Prospective individual consent is impractical because often neither the desirability nor the specific subject of the research is known at the time of making the record, and retrospective patient tracing to obtain it is often impossible. I argue that the benefit of the research outweighs the minimal breach of confidentiality, and that in my own jurisdiction, this appears to be envisaged and accepted in Canadian law. PMID- 7996563 TI - Bioethics in developing countries: ethics of scarcity and sacrifice. AB - Contemporary issues such as euthanasia, surrogate motherhood, organ transplantation and gene therapy, which occupy the minds of ethicists in the industrialized countries are, for the moment, irrelevant in most developing countries. There, the ethics of scarcity, sacrifice, cross-cultural research, as well as the activities of multinational companies, are germane. In this article, only the ethics of scarcity and sacrifice will be discussed. Structural adjustment programmes, designed to solve the economic problems of the developing countries, muddied the waters. The dilemma confronting practitioners in developing countries is how to adhere to the basic principles of medical ethics in an atmosphere of hunger, poverty, war and ever-shrinking and often non existent resources. Nowhere else in the world is the true meaning of scarcity portrayed as vividly as in the developing countries. Consequently, the doctor's clinical freedom may have to be sacrificed by the introduction of an essential drugs list and practice guidelines. The principle of greater good, while appealing, must be carefully interpreted and applied in the developing countries. Thus, while health promotion and disease prevention must be the primary focus, health planners should avoid pushing prevention at the expense of those currently sick. Health care reform in developing countries must not merely re-echo what is being done in the industrialized countries, but must respond to societal needs and be relevant to the community in question. PMID- 7996564 TI - Ethical dilemmas for general practitioners under the UK new contract. AB - Possible distributive justice frameworks for providing health care by general practitioners are discussed. The ethical considerations before and after the recent changes to the British National Health Service are contrasted, with particular emphasis on a possible ethical divide that has been produced between fund-holding and non-fund-holding general practitioners. It is argued that general practitioners in non-fund-holding practices can continue as ethical advocates for their patients and distribute health care within an egalitarian framework. However, those in fund-holding practices may now be seen as interest advocates and may have to practise utilitarian distributive justice. Patient groups may be needed to ensure that these general practitioners are seen to act justly in the distribution of the health care resources for which they are now responsible. PMID- 7996565 TI - Definition. PMID- 7996566 TI - The ethics of genetic screening: the first report of the Nuffield Council on Bioethics: another personal view. PMID- 7996567 TI - In defence of ageism. AB - Health care should be preferentially allocated to younger patients. This is just and is seen as just. Age is an objective factor in rationing decisions. The arguments against 'ageism' are answered. The effects of age on current methods of rationing are illustrated, and the practical applications of an age-related criterion are discussed. Ageist policies are in current use and open discussion of them is advocated. PMID- 7996568 TI - The ethics of blood supply. PMID- 7996569 TI - Resuscitation policy. PMID- 7996570 TI - Child sexual abuse in the Church: the ethics of throwing stones in glass houses. PMID- 7996572 TI - Mock circulatory system for in vitro reproduction of the left ventricle, the arterial tree and their interaction with a left ventricular assist device. AB - A modular physical circuit for testing monoventricular and biventricular heart assist devices (HAD) is under development. The modules now available are assembled in an open-loop circuit and reproduce the function of the left ventricle and the systemic arterial tree. The left ventricle model reproduces Starling's law of the heart and can be easily controlled to modify other parameters such as contractility and timing (i.e. heart rate and systole/diastole ratio). This circuit, in connection with a left ventricular assist device (LVAD), can be used to evaluate the LVAD performance, its effect on the circulatory system and as a training system. This paper is devoted to a description of the circuit and of its interaction with a LVAD, which is analysed after the simulation of a low contractility pathology of the ventricle. Results obtained in these experiments are reported. PMID- 7996571 TI - Grip strength of the human hand--measurements on normal subjects with a new hand strength analysis system (Hastras). AB - This study describes a method of acquiring data from healthy and non-injured men that can be used as reference data when measuring the grip strength of the human hand using newly developed, PC-based hand strength analysis equipment--'Hastras'. Hastras can be used for continuous measurement and recording of force when the subject grips a sensor with maximum power. Computerized analysis of the force signal gives information about maximum force, fatigue, area and rise (force/s). The statistical analysis of the measurements on 81 subjects are consistent with earlier published data from other hand strength equipment. It is concluded that Hastras gives easy processing and storage of data, and also a detailed analysis of grip function. PMID- 7996573 TI - Time-varying evoked potentials. AB - In an important subset of surgical procedures, the procedure itself poses a significant threat to the patient's nervous system. In order to reduce this threat, neurophysiological function of the structures at risk may be monitored during surgery using time-locked sensory or motor-evoked responses. A simple but powerful extension of the segmented and sliding average techniques currently in wide use is described and demonstrated. By fitting polynomial functions of time to capture time variations in the evoked response, signal/noise enhancement comparable with that of averaging is obtained. More importantly, a considerable improvement in time resolution is gained. In the demonstration data set presented in the figures, clinically significant changes were identifiable in one-sixth of the time required using signal averaging. PMID- 7996574 TI - Clinical evaluation for colonic polyps: usefulness of signs and symptoms in diagnosis. AB - This article reports a prospective cross-sectional study of the relationship between various signs and symptoms commonly ascribed to colorectal cancer and the presence or absence of colonic polyps found by colonoscopic examination. Of the 166 patients who participated in the study, 96 were positive for colonic polyps and 70 were negative. There was a significant increase in risk for adenomas polyps as age increased among males. For females, the step-wise logistic regression indicated that an absence of abdominal pain/cramping (p < .01), a change in stool shape (p < .01), and a history of colorectal polyps (undifferentiated) in first-degree relatives (p < .05) were associated with adenomatous polyps. PMID- 7996575 TI - Case records of the Department of Medicine University of Mississippi Medical Center. Polyglandular autoimmune deficiency syndrome. PMID- 7996577 TI - Lines of defense: domestic violence awareness month. PMID- 7996576 TI - Gallbladder surgery for Medicare patients in Mississippi. AB - Mississippi Foundation for Medical Care (MFMC) conducted a review of gallbladder surgery performed on Mississippi Medicare Patients using hospital claims files and limited record review for verification of claims file data. Significant error rates in the surgeon identification number were found in the claims files. It should also be noted that the current ICD-9-CM coding system does not allow for identification of laparoscopic cholecystectomies converted to open procedures. Past studies have attempted to use claims data alone for these types of analyses. These findings demonstrate the importance of using caution by those attempting to use claims data (without verification) to define patterns of hospital utilization, clinical outcomes and/or physician profiling. Claims data must be tested for validity for reliable pattern analysis. In addition, considerable variation was found among providers in elements such as conversion rates, complication and readmission rates. A few surgeons showed patterns for critical variables that were quite different from the universe. There was however, no statistically significant differences associated between volume of cases performed and outcomes. Time frame comparisons over several years show significant (> 80%) increase in gallbladder surgery since the introduction of the laparoscopic procedure. PMID- 7996578 TI - Domestic disturbances often result in death. PMID- 7996579 TI - Syringomyelia: clinical observations and experimental studies. AB - Although cavitary lesions of the spinal cord have been recognized for centuries, only recently have effective, noninvasive imaging techniques allowed antemortem diagnosis of this clinical syndrome. Methods of treatment have not been consistently successful in alleviating or reversing the clinical symptoms caused by these cystic lesions. Incomplete understanding of the underlying pathologic basis for the syringes has impeded the development of effective methods of treatment. This review documents historical considerations regarding clinical observations and experimental studies of this entity and the animal models that have been reported for each of the major types of syringomyelia. Recent studies have suggested that development of a relevant animal model of posttraumatic syringomyelia is imminent. Successful development of an experimental model will not only permit definition of the pathogenesis of cyst formation but also provide methods for testing of therapeutic interventions. PMID- 7996580 TI - Dynamics of extracellular calcium activity following contusion of the rat spinal cord. AB - The role of Ca2+ in cellular injury has received particular attention in studies of acute spinal cord trauma. In this context, the spatial and temporal distribution of extracellular Ca2+ ([Ca2+]e) may have an important bearing on the development of secondary tissue injury. We therefore studied the spatial-temporal distribution of [Ca2+]e following moderate (25 g-cm) contusive injury to the rat thoracic (T9-T11) spinal cord. Double-barreled, Ca(2+)-selective microelectrodes were used to measure the magnitude and time course of [Ca2+]e at increasing depths from the dorsal spinal cord surface. After 2 h, the tissue was frozen and later analyzed for total Ca concentration using atomic absorption spectroscopy. [Ca2+]e fell at all depths, but the decrease was maximal at 250 and 500 microns from the dorsal surface, where, at 0-10 min after injury, [Ca2+]e averaged 0.09 +/- 0.03 and 0.06 +/- 0.03 mM respectively. By 2 h postinjury, [Ca2+]e recovered to nearly 1 mM across all depths. Over this time, total tissue calcium concentration ([Ca]t) was 4.54 +/- 0.16 mumol/g in injured cords vs 2.75 +/- 0.1 mumol/g in sham-operated controls. These data place emphasis on the dorsal gray matter as a principal site of ionic derangement in acute spinal cord injury. The implications of these findings are discussed with reference to secondary injury processes. PMID- 7996581 TI - Bioenergetic analysis of oxidative metabolism following traumatic brain injury in rats. AB - Studies of fluid percussion-induced traumatic brain injury have shown that moderate trauma results in ionic imbalances, with resultant increases in energy demand to restore these ion gradients. Because there are also increased rates of glucose metabolism during periods of focal decline in blood flow, it has been suggested that the mitochondria may be incapable of sufficient oxidative metabolism to cope with this increased energy demand after injury and that ATP derived from substrate level phosphorylation must meet this demand. In the present study, we used phosphorus magnetic resonance spectroscopy to determine the mitochondrial capacity for oxidative phosphorylation after moderate brain trauma. Before injury, mean oxidative capacity was 54% +/- 1%. After injury, mean capacity increased significantly (p < 0.001) to a maximum of 61% +/- 1%, indicating that mitochondrial oxidative metabolism was enhanced after trauma. Increased oxidative capacity was accompanied by increases in ADP, AMP, and inorganic phosphate concentrations and was correlated to decreases in cytosolic phosphorylation ratio. We conclude that moderate brain trauma increases mitochondrial rate of ATP synthesis over the first 4 h posttrauma, and that during this time of increased ATP turnover, positive feedback regulation of glycolysis by increased concentrations of ADP, AMP, and inorganic phosphate contributes to maintenance of metabolic steady state. PMID- 7996582 TI - Increased anticholinergic sensitivity following closed skull impact and controlled cortical impact traumatic brain injury in the rat. AB - Evidence suggests that prolonged memory deficits in several neurodegenerative diseases are attributable to deficits in central cholinergic neurotransmission. In traumatic brain injury (TBI), such cholinergic deficits also may contribute to prolonged memory disturbances. This study determined whether moderate magnitudes of TBI produced by controlled cortical impact and mild magnitudes of experimental TBI produced by a new closed head impact technique in rats would produce an enhanced vulnerability to the memory disruptive effects of scopolamine, a muscarinic cholinergic receptor antagonist. Water maze performance was used to determine changes in cholinergic hippocampal function following TBI. In the first experiment, rats received a moderate level of TBI by means of a controlled cortical impact. A Morris water maze task assessed spatial memory function on days 30-34 postinjury. During the 5 day assessment period, statistical analyses showed a group main effect for swim latency. Subsequent post hoc analyses indicated that injured rats had significantly longer latencies on days 30 and 31 (p < 0.05, injury vs sham controls). By days 32-35, injured rats showed no statistically significant deficits in spatial memory performance. On day 35, scopolamine (1 mg/kg, IP) was injected into injured rats and sham-injured rats 15 min prior to being retested in the maze. Results showed that although the scopolamine had no effects on the performance of the sham-injured rats, the same dose significantly (p < 0.05) increased the latency to find the hidden platform in the injured group. In the second experiment, rats received a mild concussive closed head impact. Water maze performance was assessed on days 8-12 postinjury. No significant water maze performance deficits were observed. On day 13, injured and uninjured rats were pharmacologically challenged with scopolamine (1 mg/kg) and retested. Similar to the first experiment, injured rats manifested a significantly greater (p < 0.05) sensitivity to scopolamine than sham controls. The results from both experiments suggest that concussive and more severe levels of TBI can produce an enhanced vulnerability to disruption of cholinergically mediated memory function, even when memory function appears normal in the absence of secondary challenges. These data demonstrate that covert deficits can persist after the recovery of normal function. These deficits may be attributable to a decrease in the ability of cholinergic neurons to function properly. These data also provide important insights into features of receptor-coupled disturbances that could contribute to the maintenance of enduring cognitive deficits following TBI. PMID- 7996584 TI - Effects of neutropenia on edema, histology, and cerebral blood flow after traumatic brain injury in rats. AB - Neutrophils accumulate during the acute inflammatory response to brain injury, but their role in the injury process remains controversial. We tested the hypothesis that neutrophils contribute to cerebral edema, tissue injury, and disturbed cerebral blood flow (CBF) (hyperemia or ischemia) during the first 24 h after traumatic brain injury. Wistar rats (n = 51) were injected with either vinblastine sulfate to induce neutropenia or the saline vehicle. Five days later, under halothane anesthesia, right hemispheric trauma was produced by weight drop (10 g x 5 cm) onto exposed dura. At 24 h after trauma, brain water (wet-dry weight), traumatic infarct size (percent of hemispheric section infarcted), or local CBF (lCBF, 14C-iodoantipyrine autoradiography) was assessed. Vinblastine treatment produced profound neutropenia on the day of trauma (absolute neutrophil count 0.024 +/- 0.008 x 10(9)/L vs 1.471 +/- 0.322 x 10(9)/L, p < 0.05 in neutropenic vs saline, respectively, mean +/- SEM). Neutropenia did not reduce the development of brain edema in the injured hemisphere (brain water 82.38 +/- 0.29% vs 82.73 +/- 0.37% in neutropenic and saline, respectively, mean +/- SEM) or traumatic infarct size (34.5 +/- 3.3% vs 33.2 +/- 2.1% in neutropenic vs saline respectively). In contrast, neutropenic rats exhibited 52%, 41%, and 57% reductions in lCBF in the frontal cortex, parietal cortex, and amygdala, respectively, of the injured hemisphere 24 h after trauma (all p < 0.05 vs nonneutropenic controls). These data suggest that neutrophils and the acute inflammatory process contribute to the level of CBF observed 24 h after trauma, but effects on edema or early posttraumatic infarct size could not be demonstrated. PMID- 7996583 TI - Early microvascular and neuronal consequences of traumatic brain injury: a light and electron microscopic study in rats. AB - The purpose of this study was to document the early morphologic consequences of moderate traumatic brain injury (TBI) in anesthetized Sprague-Dawley rats. Normothermic rats (37 degrees C) were injured with a fluid percussion pulse (1.7 2.1 atm) administered by an injury cannula positioned parasagittally over the right cerebral cortex (n = 7). At 45 min following TBI, rats were injected with the protein tracer horseradish peroxidase (HRP) and perfusion fixed or immersion fixed 15 min later for light and electron microscopic analysis. Blood-brain barrier (BBB) breakdown to HRP was present overlying the pial surface and superficial cortical layers of the injured hemisphere. A focal area of severe HRP leakage was also present at the gray-white interface of the lateral cortex. Light microscopic examination of this site revealed petechial hemorrhages associated with small venules. Dark shrunken neurons and swollen astrocytes were detected within cortical areas overlying the evolving contusion, CA3 and CA4 hippocampal subsectors, and lateral thalamus. Ultrastructural studies obtained evidence for irreversible neuronal injury and mechanical damage to vessel walls at this early posttraumatic period. In nonperfused traumatized rats, luminal platelet aggregates were also detected at sites of hemorrhage. In this model of TBI, a consistent pattern of microvascular and neuronal abnormalities can be documented in the early posttraumatic period. Pathomechanisms underlying these early changes are discussed in terms of primary and secondary injury processes. PMID- 7996585 TI - Hippocampal pathology in fatal human head injury without high intracranial pressure. AB - Traumatically induced hippocampal damage is a frequent sequela of fatal human head injury and is traditionally considered to be the result of decreased cerebral perfusion secondary to raised intracranial pressure (ICP). However, in previous studies employing an experimental model of acceleration head injury, hippocampal lesions have been observed in the absence of high ICP. To further elucidate the role of raised ICP in the production of posttraumatic hippocampal neuronal damage, 14 cases of fatal human nonmissile head injury, in which the measured ICP was less than 20 mm Hg, were subjected to light microscopic evaluation for the frequency and anatomic distribution of hippocampal damage. The mean maximal ICP of the 14 patients was 17.6 mm Hg. Detailed light microscopic evaluation revealed hippocampal lesions in 12 of the 14 cases studied (86%). These lesions were typically bilateral foci of selective neuronal loss in the CA1 subfield of the hippocampus. The nature and distribution of hippocampal lesions were similar to those previously reported both in fatal human head injury associated with elevated ICP and in experimental acceleration head injury without raised ICP. These results provide further evidence that the occurrence of hippocampal neuronal loss following head injury is not exclusively dependent on elevated ICP. Other mechanisms, such as pathologic excitation of neurons, may be involved. PMID- 7996586 TI - The efficacy of barbiturate coma in the management of uncontrolled intracranial hypertension following neurosurgical trauma. AB - The purpose of this study was to evaluate the role of barbiturate therapy as an adjunctive treatment for control of intracranial hypertension when conventional methods failed. To this end, a retrospective chart review was conducted on 21 neurosurgical trauma patients with uncontrolled intracranial pressure (ICP) admitted to a trauma/intensive care unit. In this patient population, the overall mortality was 48%. Control of ICP was achieved in 67% of patients. The survival of patients experiencing ICP control with barbiturate coma was better than those patients who failed therapy (71% vs 14%, p = 0.021). Thus, in a subgroup of neurosurgical trauma patients who are refractory to conventional management of elevated ICP, barbiturates appear to improve survival, suggesting that this therapy has an important role in the management of neurotrauma patients. PMID- 7996587 TI - Traumatic lesions and transplants of granule cells in the dentate gyrus alter the distribution of afferent fibers in the molecular layer. AB - The present experiments determined whether traumatic lesions of the dentate gyrus granule cells had a different effect on the afferents in the molecular layer (ML) than nontraumatic lesions. Nontraumatic lesions of the granule cells induced by colchicine, ibotenic acid, x-radiation, and adrenalectomy have been reported to reduce both the acetylcholinesterase (AChE)-positive fibers and entorhinal afferents in the ML. After the nontraumatic granule cell lesions, the laminar distribution of the entorhinal afferents was maintained in the ML, whereas the AChE laminar pattern was lost. In the present study, dentate granule cells were traumatically lesioned by a fluid injection into the infragranular cleavage plane (IGCP) of the dentate gyrus. The traumatic lesion resulted in an altered distribution of the afferents in the ML. The perforant path fibers, shown by injection of wheat germ agglutinin horseradish peroxidase into the entorhinal cortex, occupied a greater proportion of the ML in lesioned animals than in control animals. The normal laminar pattern of AChE-positive afferents was not present after the granule cell lesion. There was an initial increase in AChE positive fibers in the ML that lasted several weeks but eventually returned to near normal levels. The altered distribution of afferents could in part be due to uneven shrinkage of the molecular layer and/or sprouting of the afferents. Granule cell suspension transplants into the IGCP also traumatically lesioned the host granule cells but immediately replaced the damaged host granule cells with immature granule cells. The distribution of afferents was similar to that found in lesioned-only animals. The traumatic lesion induced MAP2 immunoreactivity in the anisomorphic reactive astrocytes of the ML. At the longer survival times, MAP2 was not seen in either the astrocytes of the ML or in the isomorphic reactive astrocytes in CA3. PMID- 7996588 TI - Behavioral deficits following experimental subarachnoid hemorrhage in the rat. AB - To characterize some of the short-term and long-term functional consequences of subarachnoid hemorrhage (SAH) in rats, we employed a battery of well characterized tests for assessment of acute and chronic behavioral and neurologic performances. Three groups of 10 rats (blood injected, mock CSF injected and sham operated controls) were studied. During the acute stage, simple nonpostural somatomotor reflexes (pinna and corneal reflexes), simple postural responses (paw flexion, tail flexion, and head support), startle response, and postural functions (righting reflex) did not differ significantly between the experimental groups. Assessments of body weight, beam walking ability, and beam balancing revealed significant disturbances in blood-injected rats. This work demonstrates that this single-hemorrhage rodent model of SAH is associated with the induction of enduring neurologic and behavioral deficits. Because of the significant interspecies difference, a direct extrapolation of our results to humans may not be appropriate. However, we suggest that the observed behavioral and neurologic changes may parallel those seen in humans after SAH. Results reported here further confirm the rat model of SAH as a viable laboratory instrument for the study of the pathophysiology of SAH and provide normative values for the evaluation of new treatment modalities. PMID- 7996589 TI - The concept of gender identity disorder in childhood and adolescence after 39 years. AB - The term "gender role" appeared in print first in 1955. The term "gender identity" was used in a press release, November 21, 1966, to announce the new clinic for transsexuals at The Johns Hopkins Hospital. It was disseminated in the media worldwide, and soon entered the vernacular. The definitions of gender and gender identity vary on a doctrinal basis. In popularized and scientifically debased usage, sex is what you are biologically; gender is what you become socially; gender identity is your own sense or conviction of maleness or femaleness; and gender role is the cultural stereotype of what is masculine and feminine. Causality with respect to gender identity disorder is subdivisible into genetic, prenatal hormonal, postnatal social, and postpubertal hormonal determinants, but there is, as yet, no comprehensive and detailed theory of causality. Gender coding in the brain is bipolar. In gender identity disorder, there is discordancy between the natal sex of one's external genitalia and the brain coding of one's gender as masculine or feminine. PMID- 7996591 TI - Sexually compulsive men and inhibited sexual desire. AB - Sexually compulsive males report extremely high rates of desire involving paraphiliac activity. Desire and arousal in partner sex is usually low or unstable. Cognitive-behavioral strategies and techniques are presented based on four components in the assessment/intervention process: 1) eliminating or reducing paraphiliac arousal; 2) sex education, changing sexual attitudes, self disclosure, sexual assertiveness, and reduction of guilt and shame; 3) confronting secrecy and cognitive distortions, increasing empathy for victims, awareness of harm to others, and commitment to abstain from compulsive, abusive behavior; and 4) developing a healthy sexual desire and arousal pattern that nurtures and maintains an intimate relationship. The motivated male (especially with a partner he is comfortable with, attracted to, and trusts) can develop a pleasurable, erotic sexual pattern that allows him to maintain desire during partner sex. PMID- 7996590 TI - Masturbation and premarital sexual intercourse among college women: making choices for sexual fulfillment. AB - Given the potential value of masturbation as an alternative to high-risk sexual practices, there is a need to investigate factors surrounding this method of physiological sexual fulfillment. Therefore, this study examined the differences, if any, between women who have engaged in masturbation only (MO), both masturbation and sexual intercourse (MSI), and sexual intercourse only (SIO). An anonymous questionnaire was administered to volunteer respondents enrolled at a Midwestern university, yielding a subsample of 777 never-married, heterosexual women. Group comparisons indicated that MO Group women were most likely to feel guilty about engaging in masturbation and petting, but least likely to report either comfort with their sexuality or sexual satisfaction. MSI Group women indicated that, while growing up, they were less attached to their mother and father figures, whom they rated as uncommunicative. They also were more likely to have engaged in risk-related sexual behaviors. SIO Group women were more likely to have used contraceptives at first sexual intercourse and to report fewer lifetime sex partners than MSI Group women. Since a substantial number of college women refrain from engaging in masturbation, yet choose to have unprotected sexual intercourse and multiple sex partners, and others engage in masturbation but report experiencing guilt feelings regarding self-stimulation, it is of crucial importance that the negative connotations of masturbation and its attendant impact on sexual satisfaction be addressed by sexuality educators, clinicians, and researchers. PMID- 7996592 TI - The Sexual Interaction System Scale: a new inventory for assessing sexual dysfunction and sexual distress. AB - This paper reports on the development, reliability, and validity of a new self report instrument: the Sexual Interaction System Scale (SISS). Initial research on 143 couples supports reliability as measured by the internal consistency of the five factors. Validity is supported by several tests: the SISS differentiated between a nonclinical group and couples in therapy for sex dysfunction and also between two clinical groups--couples with sex dysfunction and couples with other problems. It also correlated strongly with a measure of sexual satisfaction and with the Affection subscale and overall score of the Dyadic Adjustment Scale. Discussion focuses on interpretation of results via case examples and on the utility of the SISS in research and clinical practice. PMID- 7996593 TI - Frequently cited sources in human sexology: a nineties update. AB - Counting citations in journals devoted to human sexology can provide increased awareness of important clinical and research contributions. The exercise also reveals trends in the field and serves as a guide to an ever increasing literature. This article provides lists of authors, books, and articles frequently cited in three authoritative sexuality journals. Frequency counts were based on 5,742 references over a two-year period. Results are discussed and compared with the findings from the same analysis a decade ago. PMID- 7996594 TI - Neglected subjects in sex research: a survey of sexologists. AB - This study surveyed registered diplomates of the American Board of Sexology on neglected areas in sex research. Three rounds of questionnaires were completed by the diplomates as they identified and narrowed the most neglected sexual research questions. Results indicate that among three of the four specialty groups, marital sexual behavior was ranked as the most neglected sex research subject in the literature. In reviewing the individual research questions under each subject, more outcome studies on the treatment of various sexual disorders and dysfunctions were identified and ranked consistently higher than any questions under another subject area. The single exception was among sex educators, where individual research questions concerning sex education received the highest priority. These findings may suggest the need for new directions in sex research. PMID- 7996595 TI - Absorbed states play different roles in female and male sexual response: hypotheses for testing. AB - The absorbed state-sexual arousal-orgasm pathway hypotheses assert that absorbed states of consciousness accompanying sexual arousal (sometimes called altered states of consciousness or sexual trance) play important roles in sexual response not previously recognized. Absorbed states are an obligatory pathway to high physiological sexual arousal and to orgasm in many, perhaps all, females. The role of absorbed states in males is facilitation of arousal and orgasm, with enhancement of pleasure and subjective quality of the experience. But the absorbed states pathway is not an obligatory feature of arousal and orgasm in most males. These hypotheses are empirically testable; absorbed states have objectively measurable defining characteristics as well as subjective dimensions presenting greater but not intractable methodological difficulties. Inclusion of a cognitive psychology of absorbed states can bring us closer to a more adequate and integrated psychobiological understanding of sexual response in both women and men. PMID- 7996596 TI - Spent bullets and their injuries: the result of firing weapons into the sky. AB - People often celebrate holidays by firing guns into the air without realizing that this can cause serious injury or death. The present study identified 118 patients treated since 1985 who were hit with spent bullets. Most (77%) were hit in the head. The mortality rate was 32%, which is significantly higher than for all gunshot wound victims in general seen at the same medical center. Laws have been enacted to help prevent people shooting into the sky, but more education and enforcement are required to prevent these serious and preventable injuries. PMID- 7996597 TI - A roller coaster headache: case report. AB - There are few reports of adverse outcomes associated with roller coaster rides. We present the case of a 26-year-old man who complained of a gradually worsening headache following a roller coaster ride. A computed tomographic scan of the head demonstrated bilateral chronic subdural hematomas. The clinical course and probable mechanism of injury are reviewed. PMID- 7996598 TI - Festschrift honoring John H. Davis, MD. Papers from the 2nd John H. Davis Scientific Symposium. Stowe, Vermont, June 25, 1994. PMID- 7996599 TI - The postischemic gut serves as a priming bed for circulating neutrophils that provoke multiple organ failure. AB - Our trauma research center program entitled, "Trauma Primes Cells" is based on the fundamental hypothesis that prior exposure to multiple, sequential, sublethal cellular insults primes constructive or destructive pathways of cellular responses of subsequent injury. A major objective is to design therapy that will reduce the incidence of multiple organ failure. Although a number of inflammatory cascades have been incriminated in the pathogenesis of multiple organ failure (MOF), diffuse PMN-mediated tissue injury remains an attractive unifying concept. We have developed a sequential insult rodent model in which the priming event consisted of superior mesenteric arterial (SMA) clamping for 45 minutes followed by 6 hours of reperfusion. Following this priming event, activation was induced with a low dose of endotoxin (2.5 mg/kg). We believe that these studies support our hypothesis: mesenteric ischemic/reperfusion primes circulating PMNs. When these have been activated they can then be provoked by endotoxin to provoke distant organ injury. Primed PMNs are released from the postischemic mesenteric bed and enter the systemic circulation. They subsequently sequester in the pulmonary vascular bed where they are relatively harmless until they are activated by low dose endotoxin. These activated PMNs then migrate across the endothelium cell and release reactive oxygen metabolites. PMID- 7996600 TI - Macrophage suppression of granulocyte and macrophage growth following burn wound infection. AB - Burn injury results in alterations in granulocyte and macrophage production. Since macrophages may mediate these alterations we determined the effects of macrophages obtained from animals with burn injury with and without infection on the growth of marrow granulocyte macrophage progenitor cells (GM-CFCs). The in vitro GM-CFC growth response for maximally stimulated cultures was reduced by 25% to 30% (p < 0.01) for burned and infected (B + I) animal macrophages compared with burned (B) or sham (S) animals. Macrophages stimulated with endotoxin caused a further reduction for all groups in GM-CFC growth, most notably so for B + I macrophages. Burned + infected animal macrophages or all-endotoxin macrophages cocultured with indomethacin did not suppress GM-CFC growth. Following burn injury and infection, macrophages spontaneously elaborate negative regulators of myeloid growth that is further increased by endotoxin. It is likely that PGE2, a known negative regulator of granulocyte macrophage growth, is largely responsible for this suppressive effect. PMID- 7996601 TI - The effect of inhaled nitric oxide on pulmonary ventilation-perfusion matching following smoke inhalation injury. AB - BACKGROUND: We previously reported that inhaled nitric oxide (NO) improved pulmonary function following smoke inhalation. This study evaluates the physiologic mechanism by which inhaled NO improves pulmonary function in an ovine model. METHODS: Forty-eight hours following wood smoke exposure to produce a moderate inhalation injury, 12 animals were anesthetized and mechanically ventilated (FIO2, 0.40; tidal volume, 15 mL/kg; PEEP, 5 cm H2O) for 3 hours. For the first and third hours, each animal was ventilated without NO: for the second hour, all animals were ventilated with 40 ppm NO. Cardiopulmonary variables and blood gases were measured every 30 minutes. The multiple inert gas elimination technique (MIGET) was performed during the latter 30 minutes of each hour. The data were analyzed by ANOVA. RESULTS: Pulmonary arterial hypertension and hypoxemia following smoke inhalation were significantly attenuated by inhaled NO compared with the values without NO (p < 0.05, ANOVA). Smoke inhalation resulted in a significant increase in blood flow distribution to low VA/Q areas (VA/Q < 0.10) with increased VA/Q dispersion. These changes were only partially attenuated by the use of inhaled NO. The SF6 (sulfur hexafluoride) retention ratio was also decreased by inhaled NO. Peak inspiratory pressures and pulmonary resistance values were not affected by inhaled NO. CONCLUSIONS: Inhaled NO moderately improved VA/Q mismatching following smoke inhalation by causing selective pulmonary vasodilation of ventilated areas in the absence of bronchodilation. This modest effect appears to be limited by the severe inflammatory changes that occur as a consequence of smoke exposure. PMID- 7996602 TI - The effect of hypertonic resuscitation on pial arteriolar tone after brain injury and shock. AB - Acute brain injury followed by hemorrhagic shock (HEM) causes prohibitive mortality in trauma patients because these combined events lead to low cerebral blood flow (CBF) and cerebral oxygen delivery (co2del). Proper treatment therefore requires rapid correction of cerebral perfusion deficits. Previous studies have shown that hypertonic crystalloid resuscitation significantly improves CBF and co2del in a model of brain injury and HEM when compared to lactated Ringer's (LR) solution. The mechanism or mechanisms for this advantage, however, are not well understood. We hypothesized that hypertonic fluid resuscitation would reduce pial arteriolar tone after brain injury and HEM resulting in an increase in CBF when compared to LR resuscitation. We measured cerebral and systemic variables in a porcine model of focal cryogenic brain injury and hemorrhagic shock over a 5-hour period. Swine were randomized to receive either hypertonic sodium lactate (HSL) or LR fluid resuscitation. The HSL resuscitation produced a significant and sustained elevation in cerebral perfusion pressure and pial arteriole diameter (p < 0.05), and a sustained elevation in CBF after brain injury and HEM when compared with LR. These data suggest that hypertonic fluid resuscitation following brain injury and HEM improves CBF, at least in part, by causing vasodilation of cerebral resistance vessels. PMID- 7996603 TI - Pulmonary embolism in pediatric trauma patients. AB - Recent articles in the literature on adults have recommended prophylaxis for pulmonary embolism (PE) in selected trauma patients; however, to date no information is available regarding pediatric patients. We decided to investigate whether the incidence of PE in pediatric trauma patients is as high as that reported in adults, and identify those children who might be at high risk and benefit from prophylactic treatment. Utilizing the data from the National Pediatric Trauma Registry (NPTR), records were reviewed of all pediatric trauma patients (age < 19 years) admitted to the participating institutions between December 1987 and February 1993. Patients with documented PE were identified as well as those having associated risk factors as identified in adult trauma patients (deep venous thrombosis, extremity injury, spinal cord injury, and head injury). A total of 28,692 pediatric trauma patients were reviewed from the NPTR. The mean age was 9 years and the mean Injury Severity Score for the group was 11. Two thousand one children (7%) had serious head injuries (Glasgow Coma Scale score < 8), over 5700 (20%) had an isolated extremity injury, 290 had an identified spinal cord injury (108 with associated paralysis), and deep venous thrombosis was identified in 6 patients. Pulmonary embolism occurred in only two of the children in this series. Both patients with PE had spinal cord injuries with associated paraplegia, significant pulmonary injury, and high ISSs (25 and 27). The overall incidence of PE in the group was 0.000069%, and for those children with paralysis from spinal cord injury 1.85%.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7996604 TI - The adequacy of limb escharotomies-fasciotomies after referral to a major burn center. AB - To determine the frequency of inadequate decompression and its complications, the medical records of 108 pediatric burn patients requiring escharotomies or fasciotomies were reviewed. Of 108 patients, 100 (93%) had escharotomies or fasciotomies performed at an outlying facility before transfer. Of these 100 patients, 44 (117 limbs) were inadequately decompressed and required further decompression after admission to our facility. Initial mean compartment pressures were 50.3 +/- 1.3 mm Hg, which were reduced to 16.3 +/- 0.5 mm Hg after decompression. Pulses were present in 74% of limbs requiring decompression. Twenty limbs required decompression despite noncircumferential burns. Complications of inadequate or delayed decompression included foot drop in 20 patients (35 limbs) and muscle necrosis in 13 patients (23 limbs). Four patients (seven limbs) required amputations because of progressive muscle necrosis and infection. Complications of the procedure itself were limited to bleeding in three patients. In conclusion, compartment pressures should be followed in patients with significant burns since pressures may increase over time and pulses are not predictive of ischemia. Failure to decompress extremities with elevated pressures leads to significant but preventable complications. PMID- 7996606 TI - A quantitative method for cost reimbursement and length of stay quality assurance in multiple trauma patients. AB - OBJECTIVE: To develop a statistically valid method for trauma reimbursement and quality assurance (QA) length-of-stay filters. This is needed because diagnosis related group (DRG)-based trauma payment systems assume a random sampling of injury severities from a normally distributed population and thus result in economic disincentives to level I trauma centers. METHODS: 142 trauma patients with MVC blunt multisystem injuries (MSI) (ISS > or = 16) were studied concurrently during their hospital course. SETTING: Level I regional trauma center. OUTCOME MEASURES: Outcome measures were (dependent variables) length of stay (LOS) and state-approved hospital charges (COST). RESULTS: Mean acute care COST was $74,310, but the distribution of COST was log normal, rather than Gaussian normal as assumed by DRGs. The LOS for MSI was more than twice the average for all trauma (22 vs. 9 days), reflecting skewed severities of level I patients and was related to COST (r2 = 0.802; p < 0.0001). The ISS alone was a weak determinant of COST or LOS (r2 = 0.05; p < 0.0001). The best single determinant of COST and LOS was survival (r2 = 0.15; p < 0.0001): as it increased, it increased LOS. The most costly injuries (all p < 0.0001) involved the lower extremity (LE) or hip joint (HIP), whereas sepsis and pulmonary and surgical complications constituted the most costly complications (all p < 0.0001). Regression models that accounted for the log-normal distribution of the dependent variable and based on binary variables for survival, LE and HIP injuries, and the complications of sepsis, ARDS, pulmonary failure, MOFS, plus ISS, explained nearly two thirds of the variability in COST (r2 = 0.621; p < 0.0001) or LOS (r2 = 0.687; p < 0.0001) and the residuals were normally distributed. CONCLUSIONS: These models provide a valid method of reimbursement for MSI trauma for level I trauma centers, since the data imply that good care associated with survival from specific complications of MSI are the major determinants of COST, rather than the specific type of injury or the resultant ISS. Moreover, using survival and ISS plus the disease-related complications as determinants of LOS, this method can be applied to any U.S. region since local factors can be used to adjust hospital COST as a highly correlated function of LOS. This method also permits identification of LOS outliers for QA, taking into account the influence of injury complications. PMID- 7996605 TI - Characteristics, costs, and effects of violence in Vermont. AB - Study of the distribution, characteristics, costs and effects involving 125 assaults, 22 attempted suicides (plus 5 completed out-of-hospital suicides), and 49 injuries of questionable intent was carried out among local area patients treated in a hospital serving 22 communities (150,000 population) in northern Vermont. Patients referred from the service areas of other hospitals were specifically excluded in order to provide a picture of injuries from violence in the community, rather than of injuries treated at the hospital. The percentages hospitalized were assault, 5%; attempted suicide, 50%; and unknown intent, 6%. Most assault injuries were to the head or upper extremity administered by fist; suicide attempts most often were by medication or a sharp instrument to arms, while injuries of unknown intent usually resulted from smashing a hand against a building structure. Alcohol use was noted for 26%, 38%, and 23% of patients aged 15 years or older in the three respective categories. Average hospital charges (excluding physicians' bills) for the three respective injury events were $420, $2639, and $388. Only 2% of hospital bills were paid by patients or their families, 25% were paid by commercial insurance, 19% by government sources, and 54% remained unpaid. One eighth of physicians' bills for hospital and followup care were paid by patients or their families, and about 60% were still unpaid a year after billing. Among assault patients who could be contacted for followup and who had been employed or in school previously, 27% had no disability for work or school and the remainder averaged 18 days of complete plus partial disability. PMID- 7996608 TI - Prolonged warm ischemia and limb survival: case report. AB - A 21-year-old woman sustained a supracondylar crush injury of her arm. The extremity underwent severe ischemia for more than 16 hours after an unsuccessful brachial artery repair. The forearm muscles became rigid and the fingers could not be extended passively. Clinically these findings were felt to be similar to rigor mortis. Despite this dismal picture, secondary revascularization resulted in a highly functional hand with no loss of digits. Desperate attempts at revascularization in isolated extremity injury may be successful, despite prolonged warm ischemia time. PMID- 7996607 TI - The management of open fractures associated with arterial injury requiring vascular repair. AB - Seventy-two open fractures associated with arterial injury requiring vascular repair (Gustilo type IIIC injuries) were treated at the University of Louisville from May 1983 and through 1992. The involved anatomic areas were the humerus (four), forearm (ten), femur (eight), tibia (31), ankle (ten), and foot (nine). Fracture management consisted of careful debridement, wound irrigation, fasciotomy, and fracture stabilization. Additionally, 40 wounds (55.6%) were treated with the supplemental use of local antibiotics (tobramycin-PMMA bead chains). Twenty-three patients (32.1%) underwent primary amputation, and 49 (67.99%) of the injured vessels were repaired. There were seven secondary amputations because of infection or poor revascularization, resulting in an overall amputation rate of 41.6%. The wound infection rate was 13.9% (10 of 72) and the rate for osteomyelitis was 4.2% (3 of 72). The local use of the antibiotic bead chains was of significant benefit in lowering infectious complications. Primary coverage of soft-tissue defects with free tissue transfer had an infection rate of 66%; temporary wound coverage with the "antibiotic bead pouch" technique until wound closure can be obtained in a sterile and viable environment appears to be a better option. PMID- 7996609 TI - Monocytes overcome lymphocyte dysfunction in injured adults with elevated Candida antigen titers. AB - OBJECTIVE: Severely injured adults with elevated Candida antigen titers have increased mortality from sepsis, in part because of known neutrophil (PMN) dysfunction. Since PMN function is modulated by monocytes and lymphocytes, this study was undertaken to determine the ability of monocytes and lymphocytes isolated from injured adults with elevated Candida antigen titers to activate the anticandidal function of normal PMNs. METHODS: Lymphocytes with or without monocytes, isolated from 18 injured adults with elevated titers, were cultured in the presence or absence of heat-killed Candida albicans for 48 hours. Culture supernatants were harvested, diluted 1:40, 1:160, and 1:640, and tested for the ability to stimulate the anticandidal function of normal PMNs using an 3H-glucose incorporation assay. Monocytes and lymphocytes isolated from nine volunteers were studied for comparison. RESULTS: Supernatants of lymphocytes from healthy volunteers that were cultured with heat-killed C. albicans significantly augmented normal PMN anticandidal function. Supernatants of lymphocytes from injured adults with elevated titers that were cultured with heat-killed C. albicans did not significantly augment normal PMN anticandidal function. Supernatants of monocytes or lymphocytes from both groups of patients were able to upregulate PMN anticandidal function. CONCLUSIONS: Lymphocytes from injured adults with elevated Candida antigen titers are defective in their ability to stimulate PMN anticandidal function. Monocytes from these patients can respond to Candida exposure and overcome the lymphocyte functional defect seen in injured patients with elevated titers. PMID- 7996610 TI - End-diastolic volume versus pulmonary artery wedge pressure in evaluating cardiac preload in trauma patients. AB - OBJECTIVE: To evaluate the relative accuracy of right ventricular end-diastolic volume index (RVEDVI) and pulmonary artery wedge pressure (PAWP) for determining cardiac preload. METHODS: A modified pulmonary artery catheter was used to determine RVEDVI, PAWP, and CI 238 times in 32 trauma patients. RESULTS: The initial mean values included cardiac index (CI) = 3.4 +/- 1.3 L/min/m2, PAWP = 14.8 +/- 6.6 mm Hg, and RVEDVI = 99 +/- 40 mL/m2. Cardiac index correlated better with RVEDVI (r = 0.6440; p < 0.001) than with PAWP (r = 0.1068) or CVP (r = 0.1604). In 84 studies in 19 patients, the PAWP was high (19+ mm Hg) in spite of an RVEDVI that was low (< 90 mL/m2) in 22 (26%) or mid-range (90-140 mL/m2) in 49 (58%) of these. In addition, in 12 studies a high RVEDVI (> 140 mL/m2) existed with a relatively low PAWP (< 12 mm Hg). Thus, in 83 (35%) of the studies, PAWP provided information different from the RVEDVI. Of 65 instances in which preload was increased, CI "responded" (> or = 20%) in 26 (40%). The incidence of a response was not affected by the PAWP; however, responses with a RVEDVI of < 90, 90-140, or > 140 mL/m2 were 64%, 27%, and 0 (p < 0.001). CONCLUSION: The RVEDVI more accurately predicted preload recruitable increases in CI than did the PAWP. PMID- 7996611 TI - Allopurinol plus standard resuscitation preserves hepatic blood flow and function following hemorrhagic shock. AB - To determine the contribution of ischemia-reperfusion injury (IRI) to the blood flow deficit and hepatocellular dysfunction seen after resuscitation from hemorrhagic shock, the xanthine oxidase inhibitor allopurinol was given to rats as a 50 mg/kg bolus after shock but before resuscitation and continued as a 25 mg/kg/h infusion. Resuscitation with shed blood and lactated Ringer's restored cardiac output and blood pressure in both groups. Control animals demonstrated a reduction in total hepatic and effective hepatic blood flow to 59% and 43% of baseline values, respectively. Allopurinol resulted in a return to baseline values of both variables. Allopurinol treatment resulted in a 350% increase in xanthine, a 630% increase in hypoxanthine, and a 70% reduction in uric acid concentrations. These data suggest that IRI contributes to the organ dysfunction and blood flow deficits seen after resuscitated hemorrhagic shock the effect of which can be attenuated by the addition of the xanthine oxidase inhibitor allopurinol to standard resuscitation. PMID- 7996612 TI - Comparison of mortality, morbidity, and severity of 59,713 head injured patients with 114,447 patients with extracranial injuries. AB - An analysis of the completed Major Trauma Outcome Study (MTOS) data set was undertaken to compare the incidence, mortality, morbidity, and injury severity of patients with head injuries (HI) with those of patients with extracranial injuries (ECI). The MTOS was completed recently after data from 174,160 patients submitted from 165 trauma centers from 1982 through 1989 were collated and validated. Data were analyzed with regard to the effect of injury causation for vehicular-related, nonvehicular-related, and penetrating injuries for patients with HI, ECI, or both. Detailed analyses of relationships between AIS-85 and Glasgow Coma Scale score from the entire data base, and between discharge status, functional independence measures (FIM scores), and severity of HI and ECI in a subset of 70,000 surviving patients were performed. Vehicular-related injuries (49.7%) were divided into those to vehicle occupants (36.4%), pedestrians (7.2%), and motorcyclists (6.0%). Nonvehicular-related blunt injuries included falls (18.4%) and assaults (13.2%) and penetrating injuries consisted of gunshots (8.7%), stabbings (8.0%), and other penetrations (1.8%). There were 59,713 patients with HI (34%) and 114,447 with no head injuries (NHI) (66%). Vehicular causes produced more HI (66.6%) than all other causes, despite the preponderance of nonvehicular-related HI in the overall series (50.3%). The overall MTOS mortality rate was 8.3%, but was three times higher in the HI group (14.5%) than in the NHI patients (5.1%). Injury severity measured by AIS-85 had, as expected, a profound influence on mortality of both HI and NHI groups. A similar high correlation was found between Glasgow Coma Scale score and mortality for head injured patients.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7996613 TI - What are the clinical determinants of early energy expenditure in critically injured adults? AB - The clinical determinants of energy expenditure in critically injured adults require definition. Among adult blunt trauma victims who required mechanical ventilation, the resting energy expenditure was calculated with the Harris Benedict equation (HBEE) and the early (< or = 5 days postinjury) energy expenditure was measured by indirect calorimetry (MEE) (n = 115). The MEE was 2052 +/- 531 kcal/day and MEE/HBEE ("stress factor") was 1.24 +/- 0.2. The MEE was correlated with HBEE, age, height, weight, sex, temperature, and paralytic agents (p < 0.01). However, MEE did not correlate with ISS, admission GCS score, admission base deficit, initial systolic blood pressure, or the number of units of packed red blood cells transfused in the first 24 hours after injury (p = NS). Temperature and paralysis correlated with MEE/HBEE (p < 0.01). A regression model of MEE was developed with the clinical variables HBEE, temperature, and the presence or absence of paralytic agents (r2 = 0.62; p < 0.001): MEE (kcal/d) = 1.4(HBEE) + 71.4(temperature) + 274(paralytics; + = 1, - = 2) - 3485. In mechanically ventilated trauma victims, both the early energy expenditure and the stress factor are determined by host factors but are independent of the severity of the anatomic and physiologic insult. The degree of hypermetabolism observed in this population was less than previously reported. PMID- 7996614 TI - The morbidity and mortality of rib fractures. AB - The incidence of rib fractures secondary to trauma has not been clearly reported. Of the 7147 patients seen by our trauma service from January 1987 to June 1992, 711 (10%) had rib fractures. Among the patients with rib fractures, 84 (12%) died, 670 (94%) had associated injuries, 274 (32%) had a hemothorax or pneumothorax, and 187 (26%) had a lung contusion. Fifty-five percent of the patients required an immediate operation or admission to the intensive care unit. Thirty-five percent of the patients required discharge to an extended care facility and 35% developed a pulmonary complication. We conclude that rib fractures are a marker of severe injury in which (1) 12% will die because of their injuries, (2) more than 90% will have associated injuries, (3) one half will require operative and ICU care, (4) one third will develop pulmonary complications, and (5) one third will require discharge to an extended care facility. PMID- 7996615 TI - Three-point restraints as a risk factor for chest injury in the elderly. AB - As the number of drivers over the age of 65 years increases, new trauma patterns are emerging. The use of lap-shoulder restraints, in this population, is beginning to play an important role in new findings about their injuries. Restraint use in motor vehicle crash victims, in relation to average AIS score, ISS, and number of hospital and ICU days, was studied at a level I trauma center. The control group consisted of 100 patients between the ages of 35 and 45 years, who were involved in motor vehicle impacts (MVIs) from January 1990 through January 1992. The study group consisted of 120 patients over the age of 65 years who were involved in MVIs from January 1987 through January 1992. In the control group, restraint use was associated with a lower average AIS score--3.39 versus 7.35 for the unrestrained victims. In addition, the restrained victims spent fewer days in the ICU--0.08 versus 0.30 days for the unrestrained victims; and fewer hospital days--1.08 versus 2.0 days for the unrestrained victims. The general pattern of lower average AIS scores in restrained victims was also seen in the study group. However, in the study group, lap-shoulder belt-restrained patients had higher average AIS scores, in the chest region, than unrestrained patients--0.92 (SE 1.60) versus 0.71 (SE 1.47), respectively. These findings indicate that physicians must be aware of restraint patterns of chest injury in elderly patients. Aggressive triage criteria and vigorous pulmonary toilet, especially in patients with rib fractures, sternal fractures, and pulmonary contusions, should become integral parts of trauma resuscitation protocols in elderly patients. PMID- 7996616 TI - Multisystem geriatric trauma. AB - PURPOSE: To analyze the demographics, hospital course, functional outcome, and reimbursement for elderly patients sustaining multisystem trauma. METHODS: The Trauma Registry was searched for patients > or = 65 years old with an Injury Severity Score (ISS) > or = 10 admitted with multisystem trauma from January 1991 through December 1991. Hospital data were obtained from the Trauma Registry; reimbursement data from the business office; and complete follow-up (mean, 12 months) data by telephone survey for all patients. RESULTS: Of the 1931 trauma patients admitted during the study period, 601 (31%) were > or = 65 years old and 94 (5%) met the study criteria. Of these 94 patients, 52 were women and 42 were men; their mean age was 79 years (range, 65-100). Falls (59%) and motor vehicle crashes (36%) were the predominant causes of injury; closed head injury (CHI) and fractures were the most frequent injuries. The mean ISS was 18 (range, 10-57), and hospital stay averaged 10 days. Intensive care unit admission was necessary for 37%, and 38% required surgical intervention. Factors associated with mortality included previous myocardial infarction, chronic renal insufficiency, ventilatory or inotropic support (or both), shock (systolic BP < or = 90 mm Hg) at admission, bradycardia (HR < or = 60 bpm) at admission, and severe CHI (Glasgow Coma Scale score < or = 8). Mortality was 23% (22 of the 94 patients); three quarters of the deaths occurred in the first 24 hours--most from severe CHI. At discharge, 53% of patients (38 of 72) went home and 36% (26 of 72) went to nursing homes. At a mean follow-up of 12 months, an additional seven patients had died, and three quarters of the patients were at home with an independent functional status. The percentage of reimbursement for care was two thirds of cost. CONCLUSIONS: Mortality rates are high for elderly patients who sustain multisystem trauma. Most deaths occur within the first 24 hours, and most injuries are severe CHIs. More than half of survivors are discharged home, and most are independent at long-term follow-up. Reimbursement is not commensurate with the functional outcome achieved and the care provided. PMID- 7996617 TI - Further experience with transesophageal echocardiography in the evaluation of thoracic aortic injury. AB - This prospective study sought to further define the role of transesophageal echocardiography (TEE) in diagnosing thoracic aortic injury. We performed TEE, aortography, or both on 160 consecutive patients suspected of having blunt thoracic aortic injury: TEE correctly identified 14 aortic injuries, of which five were confirmed by aortography, seven at thoracotomy, and two at autopsy. The TEE results were suggestive of but not diagnostic for injury in two additional patients with proven aortic injury, and TEE was otherwise 100% sensitive and specific for aortic injury. Aortograms yielded one false positive result and four false negative results, for a sensitivity of 73% and a specificity of 99%. We conclude that TEE is a rapid, safe, and accurate bedside method for evaluating the heart and thoracic aorta for blunt trauma. Negative or positive TEE results obviate the need for aortography. We recommend that aortography be used when TEE results are equivocal, when TEE is not tolerated or contraindicated, or when other suspected vascular injuries require evaluation by arteriography. PMID- 7996618 TI - Perception of differences between trauma care and other surgical emergencies: results from a national survey of surgeons. AB - A national sample of 2500 surgeons was surveyed. Thirteen variables were analyzed to ascertain perceived differences between trauma care and other surgical emergencies, as well as to identify factors contributing to a preferential reluctance to treat trauma. The response rate was 60%. Trauma was perceived as most likely to occur at inconvenient times by 67% of respondents, more often complex (44%), and more demanding of specialized knowledge (39%). Trauma was viewed as less likely to be reimbursed by 35% and most often litigious by 30%. Fewer respondents perceived differences for risk of exposure to lethal pathogens and violence (26% and 9%) and personal or professional rewards (25%). Surgeons who prefer to treat trauma view it as more often demanding of specialized knowledge and more complex than other surgical emergencies. Surgeons who prefer not to treat trauma or take trauma call perceive it as never personally or professionally rewarding, more often disruptive to personal life, emotionally taxing, litigious, and inconvenient compared with other emergencies. Perception of dissimilar reimbursement and personal health risk are less often associated factors. Perceived differences in the litigious nature of cases are not based on fact. We conclude that the individual degree of reluctance or enthusiasm for trauma care in comparison with other emergencies is influenced by perception, personality, and myth rather than by logic and facts. PMID- 7996619 TI - Epidermoid carcinoma-cell culture supernatant's inhibition of monocyte chemotaxis: evidence for a tumour-mediated effect. AB - Epidermoid carcinoma-cell culture supernatants obtained from three laryngeal epidermoid carcinoma patients were tested in the monocyte suspensions of 13 stage I and stage II (TNM) head and neck epidermoid-carcinoma patients and seven healthy controls for its chemotactic inhibitor activity in vitro with a modified Boyden chamber method. Using 2% casein as the chemoattractant, mean values of monocyte chemotaxis and random migration were found to be decreased in the patient group compared to the controls in a simultaneous assay recorded by the "leading front" method. Simultaneous experiments performed with the supernatant revealed a nearly double-fold increase in random migration and depressed chemotaxis in both groups. The supernatant caused a further depression in the chemotaxis of the patients' already-disabled monocytes, which is thought to be representative for advanced stage tumours. The depression of monocyte chemotaxis, especially in the control group, implies the presence of tumour-derived chemotactic inhibitor(s) for monocytes in the supernatant. PMID- 7996621 TI - The cartilaginous nasal capsule and embryonic development of human paranasal sinuses. AB - Embryology is of importance to the surgeon both for the study of human developmental anatomy and for the analysis of congenital conditions resulting from malformed or arrested development. The embryonic development of the nose, and especially of the paranasal sinuses, is not yet fully understood. This histologic study of 23 fetal heads aged from 8 to 40 weeks of gestation demonstrates that all four pairs of paranasal sinuses are developed from the cartilaginous nasal capsule. The outpouching of the nasal mucous membranes is only a secondary phenomenon, rather than the primary force. This observation helps to elucidate the following clinical observations: (1) the association of maxillary sinus hypoplasia with hypoplasia of the uncinate process, (2) the origin of chondrosarcoma of the maxillary bone, and (3) pneumatization of the paranasal sinuses. PMID- 7996622 TI - Fungal sinusitis. AB - Fungal disease of the paranasal sinuses is an important and underrecognized entity that affects both immunocompromised and previously healthy subjects. The spectrum of disease includes fungal balls, allergic fungal sinusitis, chronic indolent fungal sinusitis, and invasive fungal sinusitis. The radiologic, immunologic, and histopathologic findings are unique for each of these conditions. The surgical and medical management of these diseases is discussed and four case studies are presented. PMID- 7996620 TI - Cochlear traveling-wave delays estimated by distortion-product emissions in normal hearing adults and term-born neonates. AB - Functional aspects of human cochlear maturation were studied with distortion product otoacoustic emissions (DPE). Cochlear travel times were measured on basis of the phase-frequency relationship for DPEs in 54 term-born babies (36 to 42 weeks conceptional age [CA]) for f2 frequencies from 1.7 to 10 kHz, and the results were compared with a normaltive data set based on 36 adult ears. At the two extremes of the f2 frequency range used, 1.7 kHz and 2.4 kHz on the low end and 7 kHz and 10 kHz on the high end, the travel times for neonates were similar to those in adult ears. In the mid-frequency range (3.4 kHz and 4.8 kHz) the mean values were significantly smaller than those for adults. We attempt to explain these findings on the basis of the maturation of two partially compensating (i.e., with cochlear travel time) cochlear mechanisms: the maturation of the characteristic frequency (CF)-place relationship in the cochlea (the "shifting place" principle) and the maturation of the cochlear amplifier. PMID- 7996624 TI - The validity of tuning fork tests in diagnosing hearing loss. AB - Tuning fork tests are subjective and response bias must be accounted for when determining their validity as diagnostic tools. A significant proportion of patients who present for otologic evaluation have mixed hearing loss and it is important to know how this group responds to tuning fork testing. The need for masking in audiometry is indisputable but its role in tuning fork testing has never been established. The purpose of this study was to determine the sensitivity of tuning fork tests. The Weber, unmasked and masked Rinne, and Bing tests were administered in a prospective, random, and blind manner to 68 patients referred for audiologic assessment. Patients found to have normal hearing served as the control group. Signal Detection Theory was used to compare the results to pure-tone air- and bone-conduction audiometry. Overall the Rinne is an unbiased test with a sensitivity of 0.84 regardless of the type, severity, or frequency of hearing loss. This is not improved by masking. There is no role for either the Weber or Bing as independent tests. Mixed hearing loss behaves as conductive hearing loss. The Rinne without masking should be administered to patients suspected of having a hearing loss. PMID- 7996623 TI - Intratemporal vascular malformations (angiomas): particular clinical features. AB - Vascular malformations (angiomas) represent 1% of all pathologies of the temporal bone, including those of the cerebellopontine angle (CPA). We report six new cases of angiomas and compare them to the 48 cases listed in the literature published since 1949. Angiomas develop more frequently in the internal auditory canal (IAC) and at the geniculate ganglion (GG). When present in the IAC, rapidly progressive hearing loss is found in 88% of the patients reported in the literature and in 100% of patients in our series; facial nerve dysfunction is found in 72% and 60% of cases, respectively. The average tumour size is less than 10 mm. Acoustic neuroma, the most frequent tumour of this area, causes a slowly progressive sensorineural hearing loss in 75% of cases and facial weakness in 0.8%, according to the literature. Only 10% of acoustic neuromas measure less than 10 mm. Angiomas differ from acoustic neuromas in their rapid onset of sensorineural deafness and much greater incidence of facial nerve dysfunction despite a smaller tumour size. PMID- 7996625 TI - Ultrasound in the diagnosis and management of peritonsillar abscesses. AB - This study was conducted to determine the possibility of using an intracavitary ultrasound probe to differentiate between peritonsillar cellulitis and peritonsillar abscesses. Three volunteers and 11 of 12 patients were successfully scanned. The ultrasound method successfully demonstrated four cases of peritonsillar cellulitis and seven cases of peritonsillar abscesses. We conclude that ultrasound is a simple, safe, and noninvasive method of both assessing unilateral tonsillar swelling and determining the presence or absence of peritonsillar abscess. PMID- 7996626 TI - Unilateral vestibular deafferentation: a model of adaptation. AB - After acute loss of peripheral vestibular function, a centrally adaptive process takes place. Clinical measurements of vestibular adaptation are useful, both diagnostically and as a means of following patients after acute vestibular deficits. Ocular torsion is one measurement that can be used to follow these acutely disabled patients. The measurement is made from fundus photographs and is technically easy to perform and interpret. We present a pilot study from our Vestibular Disorders Clinic using fundus photography to measure the optic nerve head-foveal angle in six patients undergoing unilateral vestibular neurectomy, with subsequent analysis resulting in a speculative mathematical model of vestibular compensation in the roll plane. While the identification or selection of patients with significant ocular torsions from the vestibular population remains ill-defined, fundus photography remains an easy and useful method of following compensation in postoperative patients. PMID- 7996627 TI - Otitis media: microbiology and management. AB - Otitis media (OM) is a common childhood disease and one that can cause significant morbidity. A knowledge of the pathogens responsible for OM can assist in the selection of the most appropriate treatment regimen and can minimize complications that may require surgery. The microbiology of acute, serous, and chronic OM is reviewed. The major organisms recovered from about three quarters of acute OM and half of serous OM cultures are Haemophilus influenzae, Streptococcus pneumoniae, and Moraxella catarrhalis. Streptococcus pyogenes, anaerobic cocci, and viruses can each be isolated in less than 5% of the patients with acute OM. The predominant organisms isolated from chronic OM are Staphylococcus aureus, Pseudomonas aeruginosa, and anaerobic bacteria. The predominant anaerobes are gram-positive cocci, pigmented Prevotella and Porphyromonas sp, Bacteroides sp, and Fusobacterium sp. Many of the aerobic and anaerobic organisms causing OM can produce beta-lactamase, rendering them resistant to many of the penicillins. The appropriate surgical and medical therapies for acute, serous, and chronic otitis media are discussed. PMID- 7996628 TI - Carcinoid tumour of the middle ear: case report and review of the literature. AB - This is a case report of middle-ear carcinoid tumour in a patient with a 20-year history of aural tinnitus, fullness, and hearing loss. The patient was treated surgically, with no evidence of recurrence 20 months later. The natural history of this tumour appears to be relatively benign, with a long clinical course and little destruction of surrounding tissues. Immunohistochemical and electron microscopic studies are of great value in distinguishing carcinoid from other tumours of the middle ear. The pathologic features that contribute to the differential diagnosis are presented. Local conservative surgery appears to be the treatment of choice. PMID- 7996629 TI - Acute epiglottitis in adults: diagnosis and treatment in 43 patients. AB - Epiglottitis (supraglottitis) is an acute infection involving the supraglottic larynx that usually occurs in children, but can also affect adult patients. The purpose of this study was to retrospectively analyze diagnostic and treatment methods in adults with epiglottitis seen over a 10-year period at the Winnipeg Health Sciences Centre. Forty-three epiglottitis patients over the age of 16 were treated between 1982 and 1992. Treatment was individualized according to airway status at presentation, and not based on clinical staging protocols. A total of 29 patients were treated conservatively, whereas 14 patients were intubated immediately. One expectantly managed patient had to be intubated on the ward, and one patient died from septicemia. No presenting symptom or sign reliably predicted the need for intubation. Epiglottitis is seen in adults and can be easily and safely diagnosed by either indirect or flexible laryngoscopy. Endotracheal intubation is the safest and most direct means of securing the airway in severely affected patients. Staging systems are useful for retrospective data analysis, but should not be relied on to predict the course of patients with an inherently unpredictable disease. PMID- 7996630 TI - Audiologic results with the MSP/MPEAK and WSP/F0F1F2 processors and coding strategies for the nucleus cochlear implant. AB - Seven Nucleus, multichannel, cochlear-implant recipients underwent a 4-week trial with a Research Speech Processor (RSP). For five users of the Wearable Speech Processor (WSPIII), the RSP consisted of a Mini Speech Processor (MSP) with a MultiPeak (MPEAK) coding strategy, and for two MSP users, a WSPIII, utilizing an F0F1F2 coding strategy was used. Scores on an auditory-only, speech perception test battery were used to compare performance with each device. Patients were evaluated with their own processor before and after their RSP experience, to assess potential practice effects. In general, the patients with higher baseline scores appeared to be better able to take advantage of the additional information provided by the MSP/MPEAK combination. PMID- 7996632 TI - Primary post-traumatic intraorbital meningioma. AB - Intraorbital meningiomas are uncommon tumours that usually represent extension from a primary intracranial tumour. Trauma has been proposed by Cushing and Eisenhardt as an etiologic factor in the development of meningioma following head injury. We report a case of primary post-traumatic intraorbital meningioma and discuss its pathogenesis and management. PMID- 7996631 TI - The association of human papillomavirus with Schneiderian papillomas: a DNA in situ hybridization study. AB - Human papillomavirus has been identified with DNA hybridization techniques in Schneiderian papillomas, though results reported in the literature have been conflicting. This study investigated 33 cases of Schneiderian papilloma (26 inverted papillomas, seven fungiform papillomas). In situ hybridization using a cocktail of human papillomavirus (HPV) probes 6/11, 16/18, 31/33/35 failed to identify HPV genome in any of the inverted papillomas. This is contrasted by the detection of HPV 6/11 in six of seven fungiform papillomas. Of the 26 cases of inverted papilloma, 10 had recurrences, five were associated with dysplasia, and two were associated with squamous cell carcinoma. Of the seven cases of fungiform papillomas, two had recurrences, and two were associated with dysplasia, but not malignancy was found. This study supports the concept that fungiform papilloma and inverted papilloma are two distinct lesions: the former is associated with HPV 6/11. PMID- 7996633 TI - Tympanomastoidectomy for chronic suppurative otitis media of irradiated ears of nasopharyngeal carcinoma patients. AB - Chronic suppurative otitis media (CSOM) and osteoradionecrosis of the temporal bone are common sequelae of nasopharyngeal carcinoma (NPC) after radiotherapy. Tympanomastoidectomies were carried out for CSOM in 16 patients who had completed radiotherapy for NPC. Eleven (69%) patients had successful tympanoplasty; in eight of them, the otorrhoea was controlled, and the other three patients had persistent otorrhoea due to exposed osteoradionecrotic bone in the external ear canal. Localized osteoradionecrosis of the external ear canal is often associated with CSOM in NPC patients. Adequate removal of necrotic bone is essential in addition to successful tympanoplasty to eliminate otorrhoea. Therefore, we recommended tympanomastoidectomy for NPC patients with active CSOM who fail to respond to conservative treatment. PMID- 7996634 TI - A cost-efficiency discussion of radiologic imaging in facial palsy. Is it always needed? PMID- 7996635 TI - New campaign aims to cut dialysis patient deaths. PMID- 7996636 TI - From the Institute of Medicine. PMID- 7996637 TI - From the Centers for Disease Control and Prevention. Erythromycin-resistant Bordetella pertussis--Yuma County, Arizona, May-October 1994. PMID- 7996638 TI - From the Centers for Disease Control and Prevention. Dengue fever among U.S. military personnel--Haiti, September-November, 1994. PMID- 7996639 TI - Measuring quality of hospital care. PMID- 7996640 TI - Measuring quality of hospital care. PMID- 7996641 TI - Reporting of power and sample size in randomized controlled trials. PMID- 7996642 TI - Reporting of power and sample size in randomized controlled trials. PMID- 7996643 TI - Victims of violence in schools: ASK. PMID- 7996644 TI - Health insurance: definitions and distinctions. PMID- 7996645 TI - Lead poisoning due to hai ge fen. PMID- 7996646 TI - Fungi as a cause of otitis. PMID- 7996647 TI - Hemochromatosis and coronary artery disease. PMID- 7996648 TI - Early predictors of outcome for HIV patients with neurological failure. AB - OBJECTIVE: To carry out a descriptive study of human immunodeficiency virus (HIV) infected patients admitted to an intensive care unit (ICU) with neurological failure and to identify parameters that are predictive of death within 3 months. DESIGN: Case series study. POPULATION AND SETTING: A total of 84 consecutive HIV infected patients admitted to an infectious disease ICU in a university hospital for neurological failure. A thorough clinical, laboratory, and brain computed tomography (CT) scan workup was done within 48 hours of admission. MAIN RESULTS: The mean (+/- SD) CD4+ lymphocyte count was 0.067 (+/- 0.086) x 10(9)/L. Mechanical ventilation was necessary within 48 hours of admission in 67 cases (80%). The brain CT scan revealed abscesses in 51 patients (61%). The abscesses were attributed to probable toxoplasmosis in 47 patients. A total of 57 patients died, yielding a 3-month survival rate of 32%. By the log-rank test, the following factors were predictive of death within 3 months of admission to the ICU: Glasgow Coma Scale score less than 7 (P = .01), signs of brain stem involvement (P = .001), and need for mechanical ventilation in the 48 hours after admission (P = .02). In a Cox model, only Glasgow Coma Scale score less than 7 (P = .006) and clinical signs of brain stem involvement (P = .02) were predictive of death within 3 months of admission to the ICU. CONCLUSIONS: Despite a thorough examination, no initial HIV-specific parameters were identified as predictive of death. The prognostic factors found simply reflected the severity of neurological involvement in the various etiologies. PMID- 7996649 TI - Firearm training and storage. AB - OBJECTIVE: To determine the extent of firearm training among gun owners, how gun owners currently store their weapons, and the relationship between gun training and gun storage. DESIGN AND SETTING: A national random telephone survey of gun owners conducted from May through June 1994. PARTICIPANTS: A total of 800 adult gun owners residing in the United States. MAIN OUTCOME MEASURES: Number of gun owners who received firearm training and number who store a firearm loaded and unlocked. Logistic regression analyses were conducted to examine factors associated with firearm training and gun storage practices. RESULTS: A total of 451 (56%) of gun owners have received firearm training. A total of 170 (21%) of gun owners keep a firearm both loaded and unlocked in the home. Factors associated with an increased likelihood of storing guns loaded and unlocked included owning a gun for protection (odds ratio [OR], 2.40; 95% confidence interval [CI], 1.62 to 3.54), owning a handgun (OR, 3.31; 95% CI, 1.85 to 5.95), and having received firearm training (OR, 1.71; 95% CI, 1.10 to 2.67). Length of firearm training and how recently training was received have little effect on storage practices. CONCLUSION: It has been suggested that many homicide, suicide, and accidental firearm injuries might be prevented if ready access to lethal weapons was reduced, in part through appropriate storage of guns. Although increased training has been advocated as the prime method to improve gun storage practices, our results cast doubt on whether firearm training, at least as currently provided, will substantially reduce the inappropriate storage of firearms. PMID- 7996650 TI - AMA's science reporters conference features good and bad medical news. PMID- 7996651 TI - How can care for depression become more cost-effective? AB - OBJECTIVE: To determine the cost and health effects of changes in the content and quality of care for depressed patients treated in prepaid general medical practices (internal and family medicine) and mental health specialty practices and shifts in the proportion of patients treated in general medicine. METHODS: Cost-effectiveness analysis and simulations, which are empirically based on data from the Medical Outcomes Study. OUTCOME MEASURES: Change in serious functional limitations, annual treatment costs per patient, and costs per reduction in one functional limitation. RESULTS: More appropriate care for depression (increased counseling, use of appropriate antidepressant medications, or avoidance of regular minor tranquilizer use) improves functioning outcomes. Although this approach increases total costs of care, it also improves the value of care because each dollar spent on care now provides more benefits in terms of health improvements. In contrast with the effects of more appropriate care for depression, the trend away from mental health specialty care and toward general medical provider care under current treatment patterns reduces costs, worsens outcomes, and does not increase the value of health care spending in terms of health improvement per dollar. CONCLUSION: Quality improvement measures that roughly follow practice guidelines for depression can improve outcomes and the value or cost-effectiveness of care, but at increased treatment costs; shifting patients away from mental health specialists decreases costs but worsens functioning outcomes. The best strategy for making care for depression more cost effective is through quality improvement, not through changing specialty mix. Yet combining these strategies may achieve better outcomes, lower treatment costs, and better value of care compared with current practice patterns. To realize this potential, however, substantial quality improvement of care for depression is necessary in general medical practice. PMID- 7996652 TI - Linking clinical variables with health-related quality of life. A conceptual model of patient outcomes. AB - Our model proposes a taxonomy or classification scheme for different measures of health outcome. We divide these outcomes into five levels: biological and physiological factors, symptoms, functioning, general health perceptions, and overall quality of life. In addition to classifying these outcome measures, we propose specific causal relationships between them that link traditional clinical variables to measures of HRQL. As one moves from left to right in the model, one moves outward from the cell to the individual to the interaction of the individual as a member of society. The concepts at each level are increasingly integrated and increasingly difficult to define and measure. AT each level, there are an increasing number of inputs that cannot be controlled by clinicians or the health care system as it is traditionally defined. PMID- 7996654 TI - The health care mess. A bit of history. PMID- 7996653 TI - Suitability of fetal tissues from spontaneous abortions and from ectopic pregnancies for transplantation. Human Fetal Tissue Working Group. AB - OBJECTIVE: To assess the potential availability and utility of fetal tissues obtained from spontaneous abortions and from ectopic pregnancies for human transplantation therapy. DESIGN: Tissue collection and analysis by personnel skilled in tissue banking. SETTING: Procurement programs in five tissue banks located in diverse geographical areas that are funded by the National Institutes of Health. PATIENTS: All women entering obstetric clinics during 1993 who consented to participate in the study. INTERVENTIONS: None. MAIN OUTCOME MEASURES: Evaluation of the products of conception by standard developmental, histological, microbiological, and cytogenetic criteria. RESULTS: From 22,235 obstetric admissions, 1250 spontaneously aborted embryos and 247 products of ectopic pregnancies were obtained. Of these, seven embryos (0.5%) were potentially useful for human transplantation therapy. CONCLUSION: Fetal tissues from spontaneous abortions and from ectopic pregnancies are quite limited as feasible sources for human transplantation therapy. PMID- 7996655 TI - Students speak on health system reform. PMID- 7996656 TI - The new Congress and the future of health care. PMID- 7996657 TI - Should the United States push for equal numbers of generalists and specialists? PMID- 7996658 TI - The case against managed care and for a single-payer system. PMID- 7996659 TI - Medical students' opinions of health system reform. PMID- 7996660 TI - Abortion is not the answer. PMID- 7996661 TI - Verbal autopsy: an alternate technique for assigning cause of death. PMID- 7996662 TI - Is hypocitraturia associated with phosphaturia--a potential cause of calcium urolithiasis in first-time stone formers. AB - The serum and 24 hour urinary excretion levels of various lithogenic and inhibitory substances were assessed in 24 male patients with calcium stone and no previous history of urolithiasis and in 19 age-matched controls. Two groups did not differ significantly (P < 0.01) except in the excretions of sodium, citric acid (being higher in normals) and inorganic phosphate (being higher in patients). Fifty percent patients had hyperphosphaturia, 29.2% hypocitraturia, 20.8% hyperoxaluria and 16.7% hypercalciuria. The present data suggests that hypocitraturia in association with phosphaturia might be one of the main risk factors responsible for calcium urolithiasis in this area. PMID- 7996663 TI - Sero-diagnosis for viral hepatitis in 93 patients admitted with acute hepatitis in three different teaching hospitals in Lahore. AB - Serodiagnosis was done in 93 patients admitted with acute viral hepatitis (AVH) to three teaching hospitals in Lahore. Five (5.4%) had hepatitis A, 39 (41.9%) hepatitis B (2 of these were anti delta positive) [see erratum notice], 44 (47.3%) probable hepatitis E and 3(3.2%) had HAV/HBV co-infection. Antibody to hepatitis C (anti HCV) was detected in 6 patients (6.4%); 2 with HBV and 4 with probable HEV infection. Excluding 39 patients with hepatitis B and 3 with HBV as part of co-infection, there was evidence of previous HBV infection in 39 out of the remaining 51 patients. In the subset of 6 children, 3 had hepatitis A and 3 hepatitis E. Of these, 5 had evidence of previous exposure to HBV and one was also positive for anti HCV. Our results are suggestive of a strong background of HBV infection raising concern about its chronic sequelae in the community. PMID- 7996664 TI - ARI concepts of mothers in Punjabi villages: a community-based study. AB - Pneumonia is a major child killer in the developing world; to prevent such deaths, mothers must be able to differentiate pneumonia from common cold. Local concepts regarding these illnesses were studied by interviewing 315 mothers of young children in their homes in Punjabi villages. Mothers described pneumonia differently from cough-and-cold but only a few volunteered fast breathing as a sign of pneumonia. Both illnesses were thought to be caused by "coldness," and were initially treated with "heat-producing" home remedies and feeding was continued in both. Spiritual healers were not consulted for cough-and-cold or pneumonia. Virtually all mothers said that allopathic medicines were necessary for both illnesses and 2/3rd said that if a child did not improve after 2 days of a given medicine, they would change the medicine and/or the doctor. PMID- 7996666 TI - In hospital cardiopulmonary resuscitation--analysis of 188 CPRs. AB - Of 188 patients with cardiac arrest, who received cardiopulmonary resuscitation over a period of 13 months, 34 (18%) survived to leave the hospital. Most cardiac arrests (36%) occurred at the age of 60-69 years. Majority of CPRs were performed in the accident and emergency (31%), coronary care unit (28%) and acute medical wards (21%). Most common cause (48%) was myocardial infarction. Poor outcome was associated with initial rhythm of asystole. These figures suggest that the incidence of successful outcome for CPRs in hospital has not changed significantly over the past twenty-five years. PMID- 7996665 TI - Fractures of the distal femur in adults. AB - Nineteen adults sustaining 20 distal femoral fractures were followed for 18 months. Majority (70%) of the patients were males between the ages of 17 to 70 years and 68% sustained other injuries too. Fractures were classified by AO classification; most of them were intrarticular C1 type. Open reduction and internal fixation was carried out in 60% cases. Assessment of results taking into consideration the parameters of pain, deformity and range of movement were compared with the conservatively treated group. PMID- 7996667 TI - Recurrent late onset post-traumatic meningitis. PMID- 7996668 TI - Ureterorenoscopy in children. PMID- 7996669 TI - Inhalational devices: impending setback to a revolutionary therapy. PMID- 7996670 TI - Immunohistochemistry in tumour diagnosis--who actually needs it? PMID- 7996671 TI - [T cell selection and tolerance induction in the thymus]. AB - T cells play a major role in the immune system. While developing in the thymus, useful T cells are selected for expansion and harmful ones are deleted or inactivated. During this process, it is the T cells themselves which are doing the learning as opposed to the thymus doing the teaching. Both clonal deletion and clonal anergy are mechanisms of tolerance, the former being thymic, and thus central, while the latter is peripheral. Following a signal from the T cell receptor, anergy or deletion is triggered, if there are no co-stimulatory factors. Here, the outcome is determined by binding intensity. However, if the signal from the T cell receptor is accompanied by the required additional co stimulatory signals, then the T cell is rescued from apoptosis and proliferates. PMID- 7996672 TI - [Regulatory T cell network]. AB - Experimental autoimmune encephalomyelitis (EAE) is induced by myelin-specific autoimmune T cells that are characterized by a limited T cell receptor (TCR) heterogeneity. Recent studies demonstrate that regulatory T cells recognizing EAE associated idiotopes and ergotope are involved in the auto-regulation of EAE. Anti-idiotypic T cells are rapidly induced after T cell vaccination or TCR peptide immunization, indicating that the anti-TCR response is a recall response and that natural anti-idiotypic network is established in the normal T cell repertoire. Anti-idiotypic T cells are induced not only by vaccination but as the consequence of EAE. In this review, I stress that prevention and treatment of autoimmune disease should aim at the re-organization of anti-idiotypic network. PMID- 7996673 TI - [Antigen presentation by T cells and inducing anergy]. AB - Antigen presentation and its recognition are important processes of immune reactions, mediated by major histocompatibility complex antigens (MHC) and T cell receptors (TCR), that occur between antigen presenting cells (APCs) and T cells. In our previous study on T cell epitopes of human myelin basic protein (MBP), we found that activated T cells with MHC class II antigens can present MBP peptide antigens to MBP reactive T cells in the absence of traditional APCs. However, T cells stimulated by T cell APCs showed no growth response in the next stimulation by T cell APCs or traditional APCs, suggesting the induction of T cell anergy. The results implied that antigen presentation by T cell APCs might play an important rule in T cell immune responses. PMID- 7996674 TI - [Structure of MHC molecules and binding peptides]. AB - MHC class I associates with beta 2-microglobulin and one of a range of short peptides which bind to the groove formed by two alpha helix and beta sheet on the alpha 1 and alpha 2 domains of the class I molecules. The class I molecules present the peptides with allele-specific motif to T cells. Recent studies showed that melanoma specific CTL and minor histocompatibility specific CTL recognize peptides presented by the class I molecules. Further studies of peptides bound to the class I and class II molecules are expected to identify peptides which induce autoimmune disease. PMID- 7996675 TI - [The involvement of gamma delta T cells in neurological disorders]. AB - Several studies have demonstrated that gamma delta T cells increased during infections with various Pathogens. A significant fraction of these gamma delta T cells are specialized in recognizing mycobacterial antigen, in particular, 65 kda heat-shock protein (Hsp), which is highly conserved between bacteria and eukaryotes. The demonstrated immunogenicity of a number of hsp has led to their being implicated in diseases of possible autoimmune etiology. A possible role of gamma delta T cells in human autoimmune diseases such as rheumatoid arthritis, diabetes, polymyositis, sarcoidosis and acute or chronic multiple sclerosis has been previously proposed. In this brief review, we summarized the current understandings of the immunobiology of gamma delta T cells focusing on the involvement of autoimmune processes. PMID- 7996676 TI - [Adhesion molecules and immune-mediated diseases of the central nervous system]. AB - Expression of adhesion molecules in immune-mediated diseases of the central nervous system was reviewed. In multiple sclerosis and experimental allergic encephalomyelitis (EAE), endothelial cells of active lesions increase expression of the adhesion molecules such as ICAM-1, VCAM-1 and inflammatory cells including memory T cells and macrophages express high levels of adhesion molecules such as LFA-1, VLA-4. Astrocytes also express CD44, ICAM-1, VCAM-1 and E-selectin in response to cytokine stimuli. In EAE, the majority of infiltrating cells are not MBP-specific memory T cells, thus it is speculated that the up-regulation of the adhesion molecules in the endothelial cells plays a decisive role in the development of immune-mediated diseases of the central nervous system. Therapeutic potency of clinical usage of anti-adhesion molecule antibodies has been explored. PMID- 7996677 TI - [T cell clonotype analyses using SSCP]. AB - T cells recognize a specific antigen via the T cell receptor which consists of two molecules having V, (D), J and C regions. It is usually believed that certain T cell clones are expanded in order to respond to an antigen. However, the analyses of T cell clonalities are difficult to perform. In fact, several conflicting data have been reported as to whether there is an accumulation of clonal T cells in the lesion of autoimmune diseases. We have therefore established a new method to investigate the clonalities of T cells using the polymerase chain reaction and the single strand conformation polymorphism. With this method, we can monitor dynamic changes of responding T cell clonotypes during immune reaction, both in vitro and in vivo. PMID- 7996678 TI - [Bidirectional communication between neural and immune systems]. AB - The brain and the immune system communicate with each other by sharing the signal molecules and receptors. While the brain modulates immunity through the neuroendocrine and autonomic nervous controls, the immune system signals the brain by means of cytokines. This paper gives a brief review on our recent findings on (1) the central neural circuits involved in the stress-induced immunosuppression, (2) the roles of the sympathetic nerve innervating the spleen as a communicating channel from brain to immune system, and (3) the role of the organum vasculosum lamina terminalis region as a site of blood-brain signal transduction. Particularly, we have revealed that an inescapable stress elicits an activation of brain opioid systems which leads to an enhanced activity of the splenic sympathetic nerve through the brain CRF system and thereby suppresses the splenic natural killer cytotoxicity by beta-adrenergic mechanisms. PMID- 7996679 TI - [Susceptibility genes in immune-mediated neurological diseases]. AB - Antigen presenting cells can express on the surface proteolytic fragments of antigens, which are bound to peptide-binding grooves formed by the heterodimeric MHC class II molecules. The grooves consist of highly polymorphic amino acid residues, determining affinity between antigenic peptides and peptide-binding grooves. Structural analyses of these peptides could identify amino acid motifs for the peptides to bind to each class II molecule. Detailed analyses of the peptides-MHC class II interactions revealed that the class II-binding peptides can regulate immune responses mediated by corresponding T cell receptors. These phenomina are the background for susceptibility to immune-mediated diseases. PMID- 7996680 TI - [Target antigens in neuroimmunological diseases]. AB - Target antigens in neuroimmunological diseases were reviewed. These are; ple21 in limbic encephalitis; PCD17, CDR62, CDR34, and CZF in paraneoplastic cerebellar degeneration; one of the anion transporters band 3 in chorea-acanthocytosis; visinin-like substance in cancer-associated retinopathy (CAR syndrome); myelin basic protein (MBP) and proteolipid protein (PLP) in acute disseminated encephalomyelitis; MBP, PLP and myelin-oligodendrocyte glycoprotein (MOG) in multiple sclerosis; glutamic acid decarboxylase in stiff-man syndrome; GM1 ganglioside in amyotrophic lateral sclerosis; peripheral nerve K+ channel in Isaacs syndrome; synaptotagmin in Lambert-Eaton syndrome; acetylcholine receptor in myasthenia gravis; GM1 ganglioside in Guillain-Barre syndrome; GQ1b ganglioside in Fisher syndrome; myelin-associated glycoprotein in IgM paraproteinemic neuropathy; HuD in paraneoplastic sensory neuropathy; and tRNA and HSP65 in polymyositis. PMID- 7996681 TI - [Heat shock proteins and neurological disorders]. AB - Heat shock proteins (HSPs) are a highly conserved group of proteins which are produced when cells are confronted with a variety of stressful insults such as heat shock, hypoxia/ischemia, metabolic disruption, and exposure to cytotoxic reagents. Under unstressed conditions, HSPs act as molecular chaperones which play pivotal roles in the course of maturation of various cellular proteins. Under stressed conditions, they play a protective role against irreversible cell damage and promote recovery of the cells experiencing stress. In the central nervous system, proteins of the HSP 90, HSP 70, HSP 60, and small HSP families are expressed constitutively and/or induced by stressful events, differentially in distinct cell types. Aberrant expression of HSPs might be implicated in the pathogenesis of neurological disorders such as multiple sclerosis and Alzheimer's disease. PMID- 7996682 TI - [Effect of superantigens on the development of neuroimmunological disorders]. AB - Superantigens (SA) bind to major histocompatibility complex (MHC) class II antigens and activate T cells through a specific interaction between the V beta region of the T cell receptor and the toxin. Therefore, it has been postulated that SA may trigger or modulate the development of autoimmune diseases caused by T cells. In this report, the effects of SA on the development of experimental and human neurological autoimmune diseases are reviewed and the possibility of the involvement of retroviral SA in the development of human diseases is discussed. In experimental autoimmune encephalomyelitis (EAE), administration of SA prior to antigen challenge protects animals from EAE, whereas the same treatment after antigen challenge augments EAE development. These findings suggest either that 1) exposure of individuals to bacterial toxins during infection stimulates a few potentially autoreactive T cells that have escaped from the process of tolerance to expand above a threshold level, permitting autoattack, or that 2) the toxin suppresses autoreactive T cells which have the capability of inducing autoimmune diseases. In human neuroimmunological diseases such as multiple sclerosis, circumstantial evidence suggests that retroviral SA might be associated with disease development, but no direct proof has been presented so far. The possible reasons for this are also discussed. PMID- 7996683 TI - [Gut mucosal immunity and oral tolerance]. AB - The biological phenomenon that experimental animals become hyporesponsive to a particular protein antigen, when orally administered, is called oral tolerance. A breakdown of oral tolerance to dietary antigens may be related to food allergy. Conversely, the induction of oral tolerance by feeding autoantigens, such as myelin basic protein, protects animals from subsequent immunization by this antigen resulting in development of experimental autoimmune encephalomyelitis, which is a disease model of the human demyelinating disease, multiple sclerosis (MS). The mechanism of oral tolerance could be an induction of suppressor cells, which release inhibitory cytokines including transforming growth factor beta, when triggered antigen-specifically and/or clonal anergy to fed antigen. Against this background, patients with MS and rheumatoid arthritis are on a clinical trial with bovine myelin and type II collagen feeding, respectively. Oral tolerance could be a part of the mainstream in future treatment strategies for human diseases with autoimmune etiologies. PMID- 7996685 TI - [Cytokine network in the central nervous system]. AB - A variety of immunoregulatory cytokines are produced by glial cells and form a unique cytokine network in the central nervous system. They regulate the functions of neural cells in both physiological and pathological conditions. It has been shown recently that neural cells express receptors for various cytokines. Elucidation of the precise function of these cytokines may give us clues to approach the mechanisms of various neurological disorders. In some pathological conditions, regulation of cytokine production by inhibitory cytokines or other chemicals can be a new strategy for treatment. PMID- 7996684 TI - [Inflammatory mechanisms in nervous system]. AB - Experimental autoimmune encephalomyelitis (EAE), is a neuroautoimmune inflammatory disease, involving sensitization to central nervous system myelin basic protein (MBP). Our studies of the coagulation system and ensuing fibrinolysis implicate coagulation and cleavage of fibrin within or on the luminal surface of the cerebrovasculature, as events initiating the inflammation characterizing EAE. Among recipient rats injected with MBP-primed, cultured activated lymph node cells, "opening" the blood-brain barrier (BBB) and deposition of perivascular fibrin within the spinal cord occur in parallel one day before onset of clinical signs of EAE. The critical event precipitating EAE is a binding of circulating MBP-reactive immune effector cells to MBP immunodeterminants on the surface of cerebrovascular endothelial cells. Coagulation and ensuring fibrinolysis occur at sites of binding of effector cells to cerebrovascular endothelium. Release of biologically active peptides, cleaved from fibrin, "open" the BBB. Once BBB is opened, even transiently, the stage is set for a complex cascade of immunologically-nonspecific inflammatory events, which plays an important role in the development of tissue damage, including demyelination. PMID- 7996686 TI - [CD classification of lymphocytes and the function: significance of flow cytometric analysis in immunoneurological disorders]. AB - We reviewed flow cytometric studies of lymphocyte subsets by using monoclonal antibodies in various immunoneurological disorders. In multiple sclerosis, most studies indicated decreases of suppressor T cells and suppressor-inducer T cells in both peripheral blood and cerebrospinal fluid (CSF). In HTLV-I-associated myelopathy, our studies showed an increase of CD28-negative cytotoxic T cells in the CSF, indicating the involvement of dysfunctioned cytotoxic T cells in the spinal cord lesion formation. In myasthenia gravis, the disease-specific finding is the appearance of CD4+ CD8+ (double positive) T cells in the peripheral blood, which may be associated with thymic abnormalities. These flow cytometric studies in immunoneurological disorders thus provide an insight in the pathogenesis of immunoneurological disorders. PMID- 7996687 TI - [Significance of cytokines and other immunological mediators in neuroimmunological diseases]. AB - Investigation in neuroimmunological disorders has delineated multiple effector mechanisms that operate to produce inflammatory demyelination. There is much evidences to implicate cytokines in the pathogenesis of these disorders and the role and significance of measurement of various inflammatory mediators, including cytokines are reviewed. Cytokines, such as TNF, IL-1, and IFN-gamma are involved in the inflammatory demyelinating process by enhancing vascular permeability, modulating inflammatory cell-cell interactions and injuring the blood-brain barrier. Recent reports suggest that TNF, IL-2, IL-6, and other immunological mediators, such as sIL-2R, sTNF-R and sICAM-1, reflect the disease activity and can serve as a marker of acute inflammation in several neuroimmunological diseases. A better understanding of these mediators, operating on inflammatory demyelination, may help to clarify the pathogenesis of neuroimmunological diseases and to devise more efficacious therapy. PMID- 7996688 TI - [The pathomechanisms of virus-induced demyelination]. AB - The pathomechanisms of virus-induced demyelination have been widely studied, especially in animal models, in order to elucidate the pathogenesis of a human demyelinating disease, multiple sclerosis. The recent development of molecular biology has partially defined the genomic segment responsible for demyelination in some viruses. It is, however, still unclear, how such a segment causes demyelination. Three main issues have been addressed regarding the mechanisms of demyelination, i.e., oligodendrocyte lytic viral infection, immune-mediated demyelination with oligodendrocyte viral infection, and immune-mediated demyelination without oligodendrocyte viral infection. Immune responses of the host are, therefore, critical, as well as viral replication and propagation in virus-induced demyelination. PMID- 7996689 TI - [Pathogenesis of neurological disorders in AIDS]. AB - Impairment of the central nervous system (CNS) and peripheral nervous system (PNS) is common during the human immunodeficiency virus type 1 (HIV-1) infection. There are evidences of activated immune reactions in the CNS and PNS of patients with acquired immunodeficiency syndrome (AIDS). The expression of HIV-1 predominantly in monocyte/macrophage lineage cells strongly suggests immunopathogenetic mechanisms. Possible mechanisms of neuronal and glial cell damage include calcium dependent excitotoxicity by HIV-1 envelope protein, N methyl-D-aspartate (NMDA) receptor-mediated neurotoxicity of quinolinic acid, injury of oligodendrocytes by tumor necrosis factor--alpha, cell injury by HIV-1 specific cytotoxic T cells, and apoptosis of oligodendrocytes or neurons. These mechanisms are not mutually exclusive. Multiple factors may be involved in the pathogenesis of HIV-1-associated neurological diseases. PMID- 7996690 TI - [Autoimmune mechanism in HAM/TSP]. AB - Identification of the localization of HTLV-I proviral DNA in the central nervous system (CNS) is crucial to elucidate the pathogenesis of HTLV-I associated myelopathy (HAM)/Tropical spastic paraparesis (TSP). We have developed a new sensitive detection method, called two-step PCR in situ hybridization, which enabled us to detect the HTLV-I proviral DNA in paraffin embedded spinal cord tissue sections from HAM/TSP. HTLV-I proviral DNA was detected only in the nucleus of lymphocytes that infiltrated into the spinal cord. However, no proviral DNA was amplified in any neuronal cells, including neurons and glial cells. This indicates that the demyelination of the spinal cord by HTLV-I is unlikely as a result of viral infection of oligodendrocytes or neuronal cells. The sequence of T-cell receptor (TCR) V beta genes of the lymphocytes in the spinal cord lesions from the same HAM/TSP autopsy cases revealed an unique CDR3 motif, LCASSLXGG (one letter amino acid. X is any amino acid) which is identical to those found in mice encephalitogenic T-cell clones specific for myelin basic protein (MBP) peptide and two more motifs of LCASSPT (G), LCASSGRL were identical to those described in brain lesions of multiple sclerosis and in a rat T-cell clone from experimental allergic encephalomyeilitis (EAE) lesions, respectively. Taken together, the present results demonstrated that T-cells, which are reactive to the myelin component, such as MBP or PLP, may be activated by HTLV-I infection and infiltrate into the spinal cord lesions of HAM/TSP patients and suggested that an autoimmune mechanism may be involved in the pathogenesis of HAM/TSP. PMID- 7996691 TI - [HAM rat disease: an animal model of HTLV-I infection]. AB - We have established a model of HTLV-I infection in the WKAH rat strain. By inoculating MT-2, an HTLV-I producing human T cell line, HAM rat disease, a demyelinating disease resembling human HAM/TSP, developed in the WKAH rat strain. The affected lesion in the HAM rat disease is distributed symmetrically in the lateral and anterior funiculi of the thoratic spinal cord similar to that of HAM/TSP, and the histological features are also mimicked except for infiltration of lymphocytes. Using this model, it is suggested that the apoptosis of oligodendrocyte appears to be the most important process implicated in the demyelinating process of the spinal cord. The pathogenesis of HAM/TSP is also discussed herein. PMID- 7996692 TI - [Transfer of multiple sclerosis into SCID mice]. AB - Successful transfer of multiple sclerosis (MS) into severe combined immunodeficient (SCID) mice by intracisternal injection of cerebrospinal fluid (CSF) cells from six of 15 patients at exacerbation has been reported. The relative expression of mRNA for cytokines in demyelinated lesions from SCID-hu-MS by a semiquantitative reverse transcriptase-polymerase chain reaction analysis revealed marked increase in expression of mRNAs for TNF-alpha and IL-6. This result raised the possibility that these cytokines played an important role in the demyelinating process in SCID-hu-MS. To test whether or not an antibody (Ab) to murine TNF-alpha has a preventive effect on transfer of MS into SCID mice, intracisternal injection of CSF cells from two patients at exacerbation together with anti-murine TNF-alpha Ab was performed, and we observed effective prevention of transfer. In addition, we also found an Ab to human CD3 (OKT3) to have a preventive effect. The former result suggests that control of TNF-alpha may be effective in treatment of MS and the latter suggests that MS is a T cell-mediated disease. PMID- 7996693 TI - [Guillain-Barre syndrome]. AB - Sera from patients with Guillain-Barre syndrome (GBS) following Campylobacter jejuni infection have autoantibody to GM1 ganglioside in the acute phase of the illness. There is a strong association between GBS and Penner's serotype 19 (PEN 19) of C. jejuni. The terminal structure of the bacterial lipopolysaccharide is identical to the terminal tetrasaccharide of GM1 ganglioside. Anti-GM1 antibody inhibits motoneuron excitability. Molecular mimicry between infectious agents and nerve tissue components may function in the development of GBS. PMID- 7996694 TI - [Fisher syndrome and anti-GQ1b antibody]. AB - Serum anti-GQ1b IgG antibody is specifically detected in almost all the patients with Fisher syndrome and those with Guillain-Barre syndrome with ophthalmoplegia in the acute phase. An anti-GQ1b mouse monoclonal antibody immunostained the paranodal regions of the extramedullary portion of the human oculomotor, trochlear and abducens nerves. Such immunostaining was not observed in the other cranial and peripheral nerves. Anti-GQ1b IgG antibody may be involved in the pathogenetic mechanism of ophthalmoplegia in Fisher syndrome and Guillain-Barre syndrome by binding to the paranodal regions of the oculomotor, trochlear and abducens nerves. Investigation of serum anti-GQ1b antibody is considered to be a useful diagnostic marker in Fisher syndrome and Guillain-Barre syndrome with ophthalmoplegia. PMID- 7996695 TI - [Acute disseminated encephalomyelitis]. AB - Acute disseminated encephalomyelitis (ADEM) follows certain viral infection or vaccinations, which has a close etiological relationship to experimental autoimmune encephalomyelitis (EAE). Immunological examinations have not been sufficiently carried out on human ADEM except postmeasles encephalomyelitis. The most important pathogenic role in ADEM might be changes of immune regulatory mechanisms by virus infection. Therefore, it would be very useful to investigate cytokine, adhesion molecules and receptors on neural cells and endothelial cells in the central nervous system. Recently, the incidence of postvaccinated encephalomyelitis has reduced. Neurologic complications of immunization have been still reported, however, there is no scientific method to prove that the association is causal or coincidental in an individual case. PMID- 7996696 TI - [Concentric sclerosis (Balo)]. AB - Seventeen autopsy cases were collected in the Philippines. Mean age of onset 32.5 years, male/female ratio 1/2, no seasonal change, and the patients' occupation variable. A half had prodromal symptoms: mild fever, general malaise and headache. The disease was characterized by acute onset with behavioral changes, reticence, hemi- or quadriplegia with pyramidal signs, and incontinence. A quarter of patients had generalized seizure. There were no specific abnormalities in the routine blood examination, and CSF showed unexpectedly mild change. CT scan and MRI show diffuse or multifocal abnormalities in the centrum semiovale. They died of cerebral herniation or secondary infection. The brain was characterized by diffuse or multifocal necrotic and concentric demyelination in the cerebral white matter with marked gemistocytosis. PMID- 7996698 TI - [Immunological aspects of amyotrophic lateral sclerosis]. AB - Amyotrophic lateral sclerosis (ALS) is a devastating human neurologic disorder which causes atrophy and weakness of skeletal muscles leading to death. Although pathogenesis of most cases of ALS is not known yet, large number of evidence suggest autoimmune mechanisms through clinical, pathological, and laboratory findings, for example, high frequency of the presence of serum monoclonal gammopathy, association of thyroid diseases, and lymphocytic infiltration of brain and spinal cord tissues of patients. Especially recent findings of IgG antibodies against calcium channels and IgM anti-GM1 antibodies are important to elucidate the pathogenesis of ALS. Although conventional immunotherapy may not be effective, multifocal motor neuropathy (MMN) which simulates ALS should be carefully examined because MMN is a treatable disorder. PMID- 7996697 TI - [Neuropathy associated with dysglobulinemia and monoclonal gammopathy]. AB - Monoclonal gammopathy, especially monoclonal gammopathy of undetermined significance (MGUS) with IgM M-components, are associated with demyelinating neuropathy. In approximately 50% of these patients, the IgM M-component reacts with myelin associated glycoprotein (MAG) or other subcomponents of myelin such as glycolipids or gangliosides and a pathogenetic role of the M component has been proposed. Polyneuropathies associated with monoclonal gammopathies are of interest because of the potential relationship between the monoclonal protein and immune-mediated nerve damage. Many patients have been described in whom polyneuropathy is associated with IgM or IgG monoclonal gammopathy. While some such patients have MGUS, others have a variety of malignant plasma cell dyscrasia. The associated polyneuropathies clinically, electrodiagnostically, and histologically heterogeneous, but some exhibit primarily demyelination features, while others show axonal features. I have reviewed clinical, and immunological data in patients with MGUS and polyneuropathy in our clinic. The mechanism of neuropathy in patients with monoclonal gammopathy in the field of immunological studies is also reviewed. In summary, antibody activity in patients with monoclonal gammopathies associated with peripheral neuropathies almost exclusively found in monoclonal proteins of the IgM class. The most prevalent antibody is directed against MAG. IgG and IgA monoclonal proteins did not react components of peripheral nerve myelin. IgM-MGUS neuropathy should be separated conceptionally from monoclonal IgG neuropathies from my data. PMID- 7996699 TI - [Alzheimer's disease and the immune system response]. AB - Elements that belong to the natural immune system have been identified immunohistochemically in brain of patients with Alzheimer's disease (AD). Senile plaques and ghost tangles appear to be the site of chronic inflammatory response where reactive microglia, the brain resident macrophages, play a major role. Activation of the complement, coagulation and fibrinolysis systems also occur in such lesions. Nevertheless, the accumulation of plaques and tangles in postmortem brain tissue indicates the failure of microglia to phagocytose and degrade these pathological debris. "Frustrated" microglia might elicit the persistent immune responses and cause the neuronal deterioration in AD. The low incidence of AD in rheumatoid arthritis patients, who have received the long-term anti-inflammatory medication, supports this notion. PMID- 7996700 TI - [Ischemia and neuroimmunology--ischemia/reperfusion injury]. AB - Immunological events are implicated in the brain damages after ischemia. Neutrophils have been implicated in the pathogenesis of ischemia-reperfusion injury. We showed beneficial effect of antineutrophol monoclonal antibody RP3, which depletes circulationing neutrophils, on brain edema formation and infarct size. In addition, marked increase in IL-8 concentration was detected in brain and serum during early reperfusion. Time course of IL-8 production precedes brain edema formation and neutrophil infiltration. It is reported that IL-1 induces IL 8 production and anti-IL-1 antibody significantly reduced ischemic brain damages. Neutralizing antibodies against cell adhesion molecules (ICAM-1 and LFA-1) regulate neutrophil: endothel adhesion and monoclonal antibodies against these adhesion molecules reduced the size of infarction. These results indicate that neutrophil infiltration into the ischemic brain is implicated in postischemic brain injury. PMID- 7996701 TI - [Paraneoplastic cerebellar degeneration]. AB - Paraneoplastic cerebellar degeneration (PCD) is a rare manifestation of cancer, characterized clinically by subacute progressive ataxia, dysarthria and nystagmus. The pathological hallmark of PCD is a severe, diffuse loss of Purkinje cells. PCD occurs most frequently in association with small cell carcinoma of the lung and adenocarcinoma of the ovary, but it has also developed in patients with carcinoma of the breast, malignant lymphoma, and various cancers. Autoantibodies against cerebellar Purkinje cells have been frequently observed in the serum or cerebrospinal fluid (CSF) from patients with PCD. The cause of PCD is unknown, but the presence of these autoantibodies in some patients suggests that the pathogenesis may be immune mediated. The potential role of the autoantibody in the pathogenesis of PCD is discussed. PMID- 7996703 TI - [The pathogenic mechanism of experimental autoimmune encephalomyelitis and approach for new immunological therapy]. AB - Experimental autoimmune encephalomyelitis (EAE) is an autoimmune disease mediated by myelin protein-specific CD4 T cells of the Th 1 phenotype and is a major animal model for the study of multiple sclerosis. Here we review current research advancements on the pathogenic mechanism of disease induction, remission and exacervasion. Progresses both in the molecular biology and immunology permit us to make a new strategy of specific therapy for EAE. There are three important strategies to prevent disease; the first is to block the trimolecular complex and associated accessory molecules to stop the T cell activation, the second is to regulate the activated T cells with immunological networking system and the third is to modulate the immunological responses mediated by T cells in the central nervous system. PMID- 7996702 TI - [Recent advances in paraneoplastic encephalomyeloneuronopathy]. AB - Small cell lung carcinoma-associated paraneoplastic encephalomyeloneuronopathy involves the nervous system at various levels resulting in cerebellar degeneration, limbic encephalitis, myelopathy, sensory neuronopathy or brainstem encephalitis. Anti-neuronal nuclear antibody, which has been termed ANNA-1/anti Hu/Type II a antibody, is observed in the serum or cerebrospinal fluid of the patients and is highly specific for the disorder. This antibody reacts with the nucleoproteins of most neurons in the nervous system and recognizes a group of nucleoproteins in neurons with a molecular weight of 34-42 kd, suggesting that the pathogenesis of this disorder may be autoimmune. Several cDNA clones encoding the antigens have been cloned; that is, HuD, PLE21/HuC and He1-N1. These antigens contain three highly similar RRMs as well as Drosophila ELAV and RBP9 proteins do. Several autoantigens 70K, A, B", and Ro contain RRM, and Ro antigen shares B cell epitopes with these antigens. Thus, RRMs may represent or encompass an autoimmune crossreactive determinant. PMID- 7996704 TI - [Therapy for HAM/TSP and AIDS]. AB - (1) We evaluated efficacy of several treatments for HTLV-I-associated myelopathy (HAM) on the basis of our study on 254 HAM patients and of literature review. Improvement of motor disability more than fair response was obtained as follows: 82% in prednisolone, 69% in interferon-alpha, 92% in fosfomycin, 82% in high-dose vitamin C, 72% in blood purification therapy, 70% in heparin, 59% in salazosulfapyridine, 56% in thyrotropin-releasing hormone, 55% in erythromycin, 50% in mizoribine. (2) In the absence of clear guideline, the efficacy of zidovudine in the AIDS dementia complex has been demonstrated. There are also efficacy of amytriptylinein controlling HIV headache, corticosteroid in mononeuritis multiple and inflammatory myositis, hydrocortisone in autonomic neuropathy and plasmapheresis in distal sensory neuropathy respectively. Otherwise, it is emphasized that ddI, ddC and d4T have peripheral neuropathy as major, dose related side effect. PMID- 7996705 TI - [New strategies for treatment of multiple sclerosis based on the autoimmune pathogenesis]. AB - Multiple sclerosis (MS) is thought to be an autoimmune disorder, mediated by myelin-specific T cells. Recent studies demonstrate that activated T cells specific for MBP are increased in MS, and that the MBP-specific T cells and T cell infiltrates in MS brains conserve homologous TCR CDR3 motifs. Since the CDR3 motifs are also shared by encephalitogenic T cells inducing EAE, it is likely that therapeutic strategies effective for EAE may be useful for MS. In this review, I discuss the possible application of TCR vaccination, TCR antagonist peptides and oral tolerization. Considering the chronic relapsing features of MS, treatments which are safe and may tighten the immune regulatory networks are recommendable. PMID- 7996706 TI - [Treatment of multiple sclerosis with lymphocytapheresis using a leukocyte adsorption column]. AB - Twenty four patients with multiple sclerosis and four with retrobulbar neuritis were treated with lymphocytapheresis using leukocyte adsorption column. Although intravenous pulsed methylpredonine therapy followed by oral prednisolone therapy was used to treat these patients, they still fail to respond to treatment. Lymphocytapheresis was carried using a "Cellsorba" leukocyte adsorption column (Asahi Medical Co., Tokyo). About 3000 ml of whole blood was treated with the anticoagulant nafamostat mesilate and passed through the column. Eight of the 24 patients who underwent lymphocytapheresis therapy showed marked to moderate improvement. Prior to treat with lymphocytapheresis, their EDSS grades varied 3.0 to 8.5. Within 4-12 hours after therapy each of the eight patients showed EDSS grade improvement of 2 or more steps. Although about 50% of all lymphocytes were removed by lymphocytapheresis, Tal-positive activated T cells were removed more efficiently. None of the patients experienced any side effects following lymphocytapheresis. Treatment efficacy seems to be correlated with the removal of certain pathologically-activated lymphocytes, in particular, Tal-positive T cells. PMID- 7996707 TI - [Myasthenia gravis: pathogenesis and therapeutic approach on the basis of molecular structure and immunogenicity of acetylcholine receptor]. AB - Recent research for myasthenia gravis has been advanced by the availability of primary sequence of acetylcholine receptor (AChR) precursor and AChR transmembrane topography. (1) Synthetic peptides of AChR alpha-subunit defined myasthenogenic sites recognized by blocking or modulating antibody; their capability of inducing an animal model suggests that synthetic antigens contain not only B-cell sites but also T-cell sites which interact with restricted MHC class II molecules. (2) In view of the conformation-dependent B-cell site expected at beta-turn and the MHC-restricted T-cell site expected at amphipathic alpha-helix, conformationally modified peptides were synthesized by linking them; some were in combination with artificially sequenced peptide to favor an enhanced beta-turn. (3) Experiments by the use of these synthetic peptides demonstrated that such antigens were enhanced in myasthenogenicity. However, the immunogenic conformation for the induction of animal model did not necessarily assume that for the detection of antibody in native AChR-immunized rats. (4) Peptides synthesized to assume specifically for binding with antibody were used as a tool for immunoadsorption via plasma perfusion in myasthenic patients, resulting in clinical improvement. PMID- 7996708 TI - [Treatment of neuro-immunologic diseases by immunosuppressants]. AB - Immunosuppressive treatments of neuro-immunologic diseases: myasthenia gravis, polymyositis, chronic inflammatory demyelinating polyneuropathy and multiple sclerosis were reviewed. The treatments need to be planned in terms of 2-5 years. Cautions must be taken for adverse effects of short and long terms. Corticosteroids were the most well used and were studied medication of the first choice among immunosuppressants in these diseases except for CIDP in which large amounts of IV-Ig or plasmapheresis are the first choice. Pulse treatment of very high doses of steroids are used in refractory or severe cases. As for immunosuppressants, in polymyositis iv MTX is the choice since its response is quicker than AZ. CsA is used in cases with pneumonitis. In MS, pulse treatments of steroids followed by gradual decreasing doses of steroids are used for 2-3 months in each relapse. Recently, IFN-alpha 2a and IFN-beta significantly reduced the number of relapses and improved MRI findings. Chronic applications of AZ, CY, Cs or MTX have possibilities of reducing relapses, and new drugs like mizoribine and mitoxantrone etc. are in trials. PMID- 7996709 TI - [Development of diagnostic method for liver disease]. AB - Advance of current methods for management of liver diseases was discussed by eight discussers in this symposium. About three theme such as; 1. what laboratory parameters were helpful for prediction of effect of interferon (IFN) for HCV positive chronic hepatitis, 2. what tests were available for early diagnosis and prediction of prognosis in fulminant hepatitis, and 3. what laboratory parameters were useful for early diagnosis and prediction of development of hepatocellular carcinoma (HCC), hot discussion was performed. It was presented that time course of titration of HCV core antibody was available for prediction of effect of interferon in some cases. In patients with low concentration of HCV-RNA and genotype III, good effect of IFN was obtained. The possibility that the measurement of HCV serotype would become more common instead of that of HCV genotype because of its simplicity in methodology was presented. The measurements of plasma amino acids and human hepatocyte growth factor (h-HGF) were useful in early diagnosis of fulminant hepatitis. As current topics in management of HCC, the utility of determination of lectin affinity alpha-fetoprotein in early diagnosis of HCC, the importance of making definite diagnosis by target biopsy of HCC in early phase and prediction of development of HCC by abdominal sonogram were reported. PMID- 7996710 TI - [Significance of serological genotyping of hepatitis C virus in Japanese patients with chronic liver disease due to hepatitis C]. AB - Recently, T-Kohara et al. reported that most hepatitis C virus (HCV) in Japan can be classified into two groups, group 1 (G-1) and group 2 (G-2), on the basis of the NS4 region nucleotide sequence. Using a genetic engineering method, they developed a new assay in which antibodies against group specific recombinant proteins of the NS4 region were measured by ELISA (Serological Genotype, Serotype). In the present study, we examined 100 patients with chronic liver disease due to hepatitis C. The sensitivity of this assay was 98.0% (98/100). The HCV serotype distribution was 74/100 (74.0%) for serotype G-1, 22/100 (22.0%) for serotype G-2, 2/100 (2.0%) for both being positive and 2/100 (2.0%) for indeterminate. The distribution of G-1 was significantly higher than that of G-2 (p < 0.05), however, we found no difference between the distribution of G-1 and that of G-2 in age, sex, history of blood transfusion or type of liver disease. In the same serum samples, we performed HCV genotyping by reverse transcription polymerase chain reaction (RT-PCR) using type specific primers derived from the NS5 region of HCV to verify the specificity of such serotyping. The sensitivity of genotyping by RT-PCR was 88.0% (88/100). The HCV genotypes determined by both methods were consistent in 86.0% (86/100) of cases, and were not contradictory in any sample. These data indicated that serological genotyping was more sensitive and was consistent with genotyping by RT-PCR. Therefore, we consider the method useful for epidemiologic studies of HCV in Japan. PMID- 7996711 TI - [Early detection of primary liver cancer--diagnosis of small liver cancer by needle aspiration biopsy]. AB - Small liver cancer is defined as a solitary hepatocellular carcinoma (HCC) with a diameter less than 2cm. To detect liver cancer as early as possible, patients with liver cirrhosis are screened by ultrasound scanning. Pathological diagnosis in needle aspiration biopsy materials is needed because of low positivity of imaging other than ultrasound scanning. Pathological features are different from those of classical hepatocellular carcinoma. Most of the small HCCs are characterized by the following features: (1) increased cellularity, (2) increased nucleus/cytoplasm ratio, (3) irregular thin trabecular pattern, (4) pseudoglandular or acinar structures, (5) increased staining affinity (eosinophilic/basophilic), (6) frequent fatty change, and (7) residue of the portal tract. Capsules of HCCs, 1-1.5 cm in diameter, are formed. Before the formation of capsules, cancerous cells show a replacing growth pattern. Two cases of small HCC are presented, and these characteristic features are explained. PMID- 7996712 TI - [Integrated diagnosis of small hepatocellular carcinoma with imaging diagnosis]. AB - Herein, we present the diagnostic efficacy of various imaging diagnostic techniques for small liver cancer(HCC) and HCC occurrence predictability by ultrasonography during the follow-up period of chronic liver diseases. During the recent 4 years, 78 nodules of small liver cancer measuring 2 cm or less in diameter were found in 50 patients with liver cirrhosis. In this study, the tumor size was divided into 2 groups; 1.5 cm or less in maximal diameter (group A) and 1.6 to 2 cm (group B). The tumor detectability of ultrasound (US), computed tomography (CT), magnetic resonance imaging (MRI), angiography and lipiodol CT in group A vs group B was 96% vs 97%, 68% vs 88%, 65% vs 94%, 12% vs 78% and 38% vs 89%, respectively. Therefore, angiography and lipiodol CT were not effective for detection of small HCCs smaller than 1.5 cm. Recently, helical CT scanning has been induced in the diagnosis of HCCs and the tumor detectability was enhanced to 82% even in group A. Additionally, helical-dynamic CT has some advantages in evaluating vascularity, especially arterial feeding which is a specific finding to HCCs. In comparison with contrast-enhanced US using CO2-microbubbles, helical dynamic CT had equivalent accuracy in diagnosing hypervascular tumors, while hypovascular masses were observed in about 30% of group A. With respect to prediction of HCC occurrence in cirrhotic liver, sonographic evaluation of liver parenchyma seemed to be an important parameter.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7996713 TI - [Analysis of DNA contents in hematological malignant cells using whole blood lysis method]. AB - The experiments have been undertaken whether DNA contents could be measured using whole blood lysis method by FACScan. Cell population in the phases of G1, S and G2 + M were well analyzed, when we used 3 x 10(6) cells lysed with 0.1% Triton X 100 in 1 ml of phosphate buffered saline, staining with 30 micrograms/ml of propidium iodide (PI) within 30 min after staining with PI. We have further developed cell cycle analysis for cells bearing lineage specific antigens recognized with FITC-conjugated monoclonal antibodies using two color analysis. When we fixed cells with 50% ice-cold ethanol after staining cells with FITC conjugated antibodies, positive population ratio in these cells have been unchanged before and after fixing for CD3, CD4, CD5, CD8. CD10, CD19, CD14, CD33, and HLA-DR, but CD7 positive cells were markedly decreased after fixing. Using this method, CD41 positive leukemia cells have 3.4% in S phase and 6.8% in G2 + M phase, while CD41 negative cells have 1.8% in S phase and 2.0% in G2 + M phase in a patient with AML: M7, resulting leukemia cells were rich in S phase and G2 + M phase. The similar results were obtained in patients with AML:M2 using CD33 antibodies. During the clinical course, the changes of the blast numbers were well-correlated with changes of S-phase proportion in the patient with AML:M2. Among 47 patients with hematological malignancies in our hospital tested here, only 2 cases with 4.3% of total patients showed to have aneuploidy in malignant cells. One is a patient with non-Hodgkin lymphoma, the other is myelodysplastic syndrome.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7996714 TI - [Cytotoxicity test based on luminescent assay of alkaline phosphatase released from target cells]. AB - Assay of 51Cr release from target cells has been commonly used in various methods of examining the cytotoxic properties of lymphocytes. In this paper a non isotopic assay of cytotoxicity based on the leak of endogenous alkaline phosphatase (AIP) in target cells, is described. Enzyme activities were assayed by the luminescence on hydrolysis of the lumigen-PPD substrate. P3-X63-Ag8-U1 (P3U-1) cells were demonstrated to contain AIP and proved sensitive to the IL-2 induced killer lymphocytes, while no AIP activity was detected in human effector lymphocytes. Comparative studies of the test with 51Cr- and AIP-release in P3U-1 target cells were carried out, and the results obtained suggested that the AIP release test is useful as a new, simple lymphocyte cytotoxicity test. PMID- 7996715 TI - [Application of inflammation markers in the "essential laboratory tests" to new outpatients and analysis for the efficacious selection of these items]. AB - We have re-evaluated the usefulness of the inflammation markers in the "essential laboratory tests" advocated by Japan Society of Clinical Pathology and analyzed for efficacious selection of these items by applying these tests to 349 new outpatients visited Comprehensive Medicine, National Defense Medical College. Among the patients with "tentative initial diagnoses" of infectious or inflammation-related diseases (133 cases), the diagnoses were confirmed in 102 patients by positive inflammation marker(s), whereas additional 22 cases with the diagnoses other than inflammation-related diseases were found to be in the inflammatory status by these tests. Elevated C-reactive protein (CRP) levels were not correlated with the leukocyte number, however, neutrophilia (neutro. > 70%) and/or left shift of the neutrophils (stab > 15%) were demonstrated in approximately 50% of the patients with elevated serum CRP levels. Increases of serum sialic acid highly accompanied with increases of CRP, alpha 1 or alpha 2 fraction of serum protein and elevation of erythrocyte sedimentation rate (ESR), indicating that serum sialic acid levels reflected more strictly inflammatory status than ESR. There is a relatively good correlation (r = 0.813) between serum sialic acid values and the total amounts of alpha 1 and alpha 2 protein fraction, while poor correlations were shown between CRP and sialic acid values (r = 0.606), or ESR and sialic acid values (r = 0.671). These results indicate that (1) simultaneous measurements of CRP, leukocyte number and leukocyte differential fraction are useful for the confirmation of early stage of inflammation and evaluation of the nature of infectious diseases; (2) measurement of serum sialic acid levels is more desirable for the evaluation of inflammatory status than ESR; and (3) serum protein profile can be substituted by sialic acid for the evaluation of acute inflammatory status alone. PMID- 7996716 TI - [The correlation between the MICs deduced from Showa disk method and the MICs determined by micro-dilution method]. AB - Disc diffusion technique is useful to routine drug susceptibility testing for bacteria in clinical laboratories because of the advantages on simplicity and cost. Kirby-Bauer (KB) method recommended by NCCLS is using widely as a standard method of disk diffusion test, and simply categorize microorganisms as being susceptible, moderately susceptible, intermediate or resistant to different antimicrobial agents by the use of break point. In the determination of breakpoints, the relationship between MICs and clinical results and pharmacokinetics parameters (Cmax, T1/2 and AUC) are significantly considered. However, there are variance of pharmacokinetics among a race, moreover, breakpoint is not yet established in Japan. In report to doctor from clinical laboratory, the MIC might be better than that by breakpoint since there are such problems of breakpoint. Showa disk was developed as mono-disk method being able to deduce MIC from the linear regression between MIC and zone diameter. Therefore, it is thought that Showa disk is one of valuable methods for the routine drug susceptibility testing for bacteria in Japan. There is one problem, which is that MIC deduced by Showa disk is based on the relationship with agar dilution method although the determination method of MIC is going to turn into micro-dilution method, so we compared the MICs deduced from zone diameter of Showa disk method with the MICs determined by broth micro-dilution method by using a challenge set of 110 gram-positive and gram-negative bacteria for 7 antimicrobial agents. The total agreement of MIC within 1-log2 dilution difference was 77% and the correlation coefficient was 0.929. As results, a good relationship was obtained except the results of tetracycline and ofloxacin for beta-lactamase non-producing H. influenzae, and ceftizoxime for E. coli, and K. pneumoniae. PMID- 7996718 TI - [Role of pathology as clinical medicine: experience at Kawasaki Medical School]. AB - The department of Pathology at Kawasaki Medical School was destined, from the outset of its foundation, to be one of clinical departments. To discuss the role of pathology as clinical medicine, the actual state of our department is described here with reference to its organization, principles, and quality assurance program in both surgical pathology service and hospital practice. The department at School also functions as a hospital pathology department and handles 10,000 surgical and 18,000 cytology materials as well as about 180 autopsies per year. Examination of the tissues and organs removed from the patients is wholly entrusted to our department in its full responsibility. All the tissue sections are examined by multiple certified pathologists and reports are returned by the third day. Case reviews are regularly done by peer reviewers and through the conferences held between pathology and relevant clinical departments. The latter conferences serve as a medical audit in the hospital as well. The pathologists sometimes participate in the performance of aspiration cytology, and muscle and nerve biopsy. It is hoped that the description of our experience in surgical pathology will provide some insights on the improvement of the system to concerned readers and cause lively discussion on this matter. PMID- 7996719 TI - [Undergraduate and postgraduate medical education in pathology department: experience at Kawasaki Medical School]. AB - Described herein is the present status of both undergraduate and postgraduate medical education participated by the department of pathology, Kawasaki Medical School. The department concerns the education of medical students from the second through sixth year. All the subjects taught are more clinically oriented. Resident educational system, composed of two years of junior and four years of senior training period, is well programmed to achieve clinical competence and laboratory management. Many self-learning materials and teaching seminars are provided. In addition, medical museum, which is affiliated to the School, helps learning not only of students and doctors in the hospital but also of laymen and private physicians in the city with many exhibits. It is hoped that the description of our experience will provide some insights on the improvement of the undergraduate and postgraduate education and cause lively discussion on this matter among concerned readers. PMID- 7996717 TI - [Detection of methicillin-resistant Staphylococcus aureus using PCR and non radioactive DNA probes: III. Mutations of the fem A gene in clinical strains of Staphylococcus aureus]. AB - Methicillin resistance in S. aureus is primarily due to the presence of the mec A gene. However, in addition to mec, the phenotypic expression of methicillin resistance requires the presence of an additional gene(s), fem A which is chromosomally encoded. Previous studies suggest an increase in the biochemical function of fem A gene products due to base substitutions in the region upstream of the fem A gene and in its coding frame. The partial nucleotide sequences of fem A regions in reference and clinical strains of S.aureus were therefore analyzed by PCR-direct solid-phase sequencing and suitable DNA probes. Amplified target DNAs of 251, 330 and 271 bp were resolved on ethidium bromide-stained gels and hybridized with DNA probes conjugated to alkaline phosphatase. In ATCC 12600 strain, a palindromic sequence was conserved in the region upstream of fem A. However, it was destroyed by the occurrence of mutations in other reference, and clinical strains tested regardless of whether they are methicillin-susceptible or resistant. Furthermore, in the coding frame of fem A, two missense mutations were present in MSSA and MRSA without any regularity. These findings suggest that mutations in the fem A region may not be a single factor essential for regulation of methicillin resistance, although fem A probably functions cooperatively with mec A. PMID- 7996721 TI - [Basic evaluation of the new fully automated urine sediment analyzer (U-FCM) based on flowcytometric technology]. AB - We developed a new automated urine sediment analyzer (U-FCM) based on Flow Cytometry with the cooperative technical aid of TOA Medical Electronics Co., ltd. Flow Cytometry using an argon laser (wave length 488 nm) is used as the method for detection. This instrument provides quick, easy and accurate screening for patients whose urinalysis abnormalities indicate the need for further testing. Abnormal patient samples are separated from patient samples whose parameters are totally normal, thus decreasing the need for additional testing. The instrument is useful as a diagnostic aid, and in monitoring the therapeutic effect. Also it is useful in the health checking service for visitors at the AMHTS office. PMID- 7996720 TI - [A comparative study of a bioelectrical impedance method and dual energy X-ray absorptiometry for body composition analysis]. AB - The accuracy of a bioelectrical impedance analysis (BIA) was examined by comparison with a dual energy X-ray absorptiometry (DXA) to measure the body composition. The subjects consisted of 52 patients (21-78y.) with chronic renal failure (32 cases), osteoporosis (6 cases) and diabetes mellitus with obesity (14 cases). Bioelectrical impedance between hand and leg was measured by a body composition analyzer (Model BIA-BC-3, RJL) with a four-electrode system. One pair of current supply and detector electrode was attached to the right hand and another pair was to the leg. The total fat mass measured by BIA was well correlated with the value by DXA (r = 0.959, p < 0.01). The total fat mass by BIA was also correlated with the fat mass in the arms (r = 0.863), fat mass in the legs (r = 0.911), and fat mass in the trunk (r = 0.920) by DXA. The correlation rates were p < 0.01. These correlation coefficients were lower than the correlation rate of the total fat mass measured by DXA. The total lean mass measured by BIA was well correlated with the value by DXA (r = 0.963, p < 0.01). It was correlated with the lean mass in the arms (r = 0.899), lean mass in the legs (r = 0.929), and lean mass in the trunk (r = 0.906) by DXA, but these values were lower than the correlation rate of the total lean mass obtained by DXA. These findings suggest that BIA is a safe and simple method for analyzing the body composition of the total fat mass and the total lean mass, and total body composition is reflected more clearly than regional body composition. PMID- 7996722 TI - [A mini-review of nursing research on infection control in Japan]. PMID- 7996723 TI - [A guide for clinical nursing research on infection control]. PMID- 7996724 TI - [Nursing research on infection: five year project]. PMID- 7996725 TI - [Microbiological examination of the water used to wash the suction tube in endotracheal suctioning]. PMID- 7996726 TI - [Contamination of nurses' protective gowns and gloves after various types of care for MRSA infected patients]. PMID- 7996727 TI - [Bacterial elimination effect of towel-mats with disinfectant located at the entrances of MRSA infected patients' rooms]. PMID- 7996728 TI - [The history of infection control studies on home health care in Japan]. PMID- 7996729 TI - [Bacteriological study in home care setting]. PMID- 7996730 TI - [Dimensions of nursing care quality: through use of the Delphi method]. PMID- 7996731 TI - [Research trends on assurance of nursing quality: literature review]. PMID- 7996733 TI - Fear and its antidote. PMID- 7996732 TI - [The structural paradigm of nursing care for patients with chronic illness: clinical experience with diabetic outpatients (III)]. AB - The purpose of this study was to clarify a nursing paradigm of care for patients with chronic illness. Data were derived from fieldnotes of direct patient care for 111 diabetic outpatients. These fieldnotes included nursing intervention, conversation process, patient response to the nurse, the nurse's decision making process, and the nurse's reflections after intervention. Interpretive analysis identified nursing goals, nursing interventions, clinical judgment, and the nature of the patient-nurse relationship. Five nursing goals of patient-oriented care were identified: compliance, self-management, self-acceptance, independence, and self-actualization. Five approaches for nursing intervention also were identified: directed, facilitating, acknowledging, mutually responding, and mutually cooperating. From these findings, a nursing paradigm of care was conceptualized. As nursing goals became more "holistic", the patient-nurse relationship became more intimate, and the patients' competency to participate in the management of their own diabetic care became greater. This paradigm should assist nurses in judging and selecting the proper care for the needs of each patient. PMID- 7996734 TI - The practice of medicine: the best of times, the worst of times. PMID- 7996735 TI - Breast cancer detection. PMID- 7996736 TI - Human listeriosis: case report and review. PMID- 7996737 TI - CTD: carpal tunnel syndrome, the facts and myths. AB - Recognition of the need for risk control of occupational injuries and prevention programs has led to many new studies demonstrating that occupational diseases are multifactorial in etiology, and that a specific job may not be the primary cause for occurrence. As a result of the many causes, myths about work-related injuries have developed. CTDs are the majority of occupational injuries. Individual risk factors are a better predictor of development of CTD and CTS than are job-related factors. Risk for carpal tunnel syndrome is closely related to general physical condition. Improved general health and health prevention programs may reduce an individual's risk level for developing a cumulative trauma injury. Risk measurement systems now allow employers to establish programs with measurable results. Since assessing the individual risk factors provides the best opportunity to attain the goal of prevention, the next step is for employee, employers, insurance carriers and the medical profession to establish concurrent prevention programs based on human risk factor evaluation systems. PMID- 7996738 TI - Repetitive use injury: diagnosis, treatment and prevention. PMID- 7996739 TI - Acute quadriplegic myopathy. PMID- 7996740 TI - Immunization coverage rates among two-year-olds in Kansas. PMID- 7996741 TI - Meckel's diverticulum. PMID- 7996742 TI - [Review of current health care system: health budget]. PMID- 7996743 TI - [Books on old age: preparation for dying]. PMID- 7996744 TI - [Report by director of nursing: evaluation of quality of hospital services]. PMID- 7996746 TI - [Informed consent: general background]. PMID- 7996745 TI - [We admire nurses: activity of the Consumer Organization for Medicine & Law (COML) and our expectation for nurses]. PMID- 7996747 TI - [Visiting nursing service: management efforts]. PMID- 7996748 TI - [Telephone counseling: tips for better services]. PMID- 7996749 TI - [Introduction of the "nurse's fee" concept in the medical treatment fees system]. PMID- 7996750 TI - [People who supported me during my hospitalization for mastectomy]. PMID- 7996751 TI - [Placement of human resources for nursing to be facilitated by on-line computer systems]. PMID- 7996752 TI - [Issues and problems surrounding nurses and nursing]. PMID- 7996753 TI - [Challenges for 1994 by hospital nursing departments described by directors of nursing. Shift from top-down to bottom-up]. PMID- 7996754 TI - [Challenges for 1994 by hospital nursing departments described by directors of nursing. Staff development program encouraging nurses to become thinking and doing nurses]. PMID- 7996755 TI - [Challenges for 1994 by hospital nursing departments described by directors of nursing. Yearly program of the nursing department helps goal attainment]. PMID- 7996757 TI - [Challenges for 1994 by hospital nursing departments described by directors of nursing. Plans to make goal attainment possible]. PMID- 7996756 TI - [Challenges for 1994 by hospital nursing departments described by directors of nursing. Preparation of specialists as well as generists]. PMID- 7996758 TI - [Challenges for 1994 by hospital nursing departments described by directors of nursing. Introduction of PONR]. PMID- 7996759 TI - [Challenges for 1994 by hospital nursing departments described by directors of nursing. Programs for reaching out to community]. PMID- 7996760 TI - [A book on old age: "Changing disease and changing death" by Shoji Tachikawa]. PMID- 7996761 TI - [Report by director of nursing: evaluation and development of staff ability]. PMID- 7996762 TI - [We admire nurses: activity of the Consumer Organization for Medicine & Law (COML) and our expectation for nurses--their words could hurt patients]. PMID- 7996763 TI - [Visiting nursing service: why do we get paid by the number of visits and not by the time we worked?]. PMID- 7996764 TI - [Medical topics. Increasing perception gap between providers and recipients of medical care]. PMID- 7996765 TI - [Knowledge update: reading laboratory test results]. PMID- 7996767 TI - [The nursing shortage and the 1990's: realities and remedies]. PMID- 7996766 TI - [Telephone counseling: tips for better services]. PMID- 7996768 TI - [Workshop for bone marrow transplant coordinator: HLA]. PMID- 7996769 TI - [Introduction of the "nurses' fee" concept in the medical treatment fees system]. PMID- 7996770 TI - [Perspective of medical economy 1994: shift of focus on quality rather than quantity]. PMID- 7996771 TI - [Research on bacterial contamination of linens and pads of hospital beds]. PMID- 7996772 TI - [Richness recovered in the time of depression]. PMID- 7996773 TI - [National nursing policy: the law amended to enable male nurses to become public health nurses starting in 1994]. PMID- 7996774 TI - [Efforts to prepare work schedule acceptable for nurses on wards. Tentative schedule checked by staff for adjustment]. PMID- 7996775 TI - [Efforts to prepare work schedule acceptable for all nurses on wards. Fairness in weekend off and frequency of night duty]. PMID- 7996776 TI - [Efforts to prepare work schedule acceptable for all nurses on wards. My first challenge to prepare schedule for my ward]. PMID- 7996777 TI - [Efforts to prepare work schedule acceptable for all nurses on wards. Making a good work schedule is the primary responsibility of the ward supervisor]. PMID- 7996778 TI - [Efforts to prepare work schedule acceptable for all nurses on wards. Quality care and staff's good health are key factors in our computer-assisted work scheduling]. PMID- 7996779 TI - [Efforts to prepare work schedule acceptable for all nurses on wards. Work schedule needs adjustment with realities]. PMID- 7996780 TI - [Efforts to prepare work schedule acceptable for all nurses on wards. Consideration for staff's life style is essential]. PMID- 7996781 TI - [Efforts to prepare work schedule acceptable for all nurses on wards. Good work schedule leads to better patient care and better colleagueship]. PMID- 7996782 TI - Treatment of the nephrotic syndrome associated with primary glomerulonephritis. PMID- 7996783 TI - The biological action of calcitriol in renal failure. PMID- 7996784 TI - Insulin induces a change in extracellular matrix glycoproteins synthesized by rat mesangial cells in culture. AB - Extracellular matrix (ECM) accumulation within the glomerular mesangium is a hallmark of progressive forms of renal disease. We recently succeeded in propagating mesangial cells (MC) from the time of explant without supplemental insulin which exhibit a matrix profile analogous to normal mesangium in vivo. We used these cells to characterize insulin-induced changes in biosynthesis and accumulation of three important matrix glycoproteins, laminin, fibronectin, and thrombospondin. Two clones of MC derived from glomeruli from a single rat were compared. MC grown in the absence of supplemental insulin (SI-MC) assemble a matrix rich in fibronectin with much smaller accumulations of laminin and thrombospondin. In comparison, MC (SI+MC) grown chronically in the presence of 1 microM insulin have a greatly expanded ECM that immunostains less intensely with antibodies to fibronectin, but, it contains significant accumulations of laminin and thrombospondin. Following metabolic labeling of secreted proteins with 35S methionine, total protein synthesis was measured, and specific ECM components were identified and quantitated by immunoprecipitation, SDS-PAGE and autoradiography. The rate of total protein synthesis was increased by 50% in SI+MC as compared to SI-MC, yet, individual proteins were increased or decreased. The rate of synthesis of fibronectin was decreased and the rate of synthesis of laminin and thrombospondin was increased by insulin. These changes were directionally correlated with the net accumulation of these proteins as shown by immunostaining. In addition to an increase in laminin synthesis, insulin treatment induced a change in the isoform of laminin expressed.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7996785 TI - Localization of connexin43 in rat kidney. AB - The localization of connexin43 (Cx 43) in rat kidney was investigated by the indirect immunofluorescence technique with polyclonal antisera raised against Cx 43. Cx 43 is a gap junction protein expressed in a variety of tissues. The typically punctuated gap junction immunofluorescence (GJI) was observed in the renal arterial and arteriolar system. In the renal artery the GJI was concentrated in the media. In the juxtamedullary nephrons, the GJI is particularly abundant in the vascular bundles. There is abundant GJI in the extraglomerular mesangium while in the afferent arteriole GJI appears decreased. Abundant GJI was observed in the inner medullary collecting ducts and pelvic epithelium. The localization of Cx 43 immunofluorescence observed in this study is only in partial agreement with the results of ultrastructural investigations on the distribution of gap junctions in the kidney. An extensive tight junctional system has been demonstrated in the collecting duct system. However, gap junctions have been reported to be absent. Further studies to resolve this discrepancy are required. PMID- 7996786 TI - Segmental localization of mRNAs encoding Na(+)-K(+)-ATPase alpha- and beta subunit isoforms in rat kidney using RT-PCR. AB - To characterize the expression of genes encoding the alpha- and beta-subunit isoforms of the Na(+)-K(+)-ATPase in rat kidney, we used reverse transcription (RT)-PCR of microdissected renal structures combined with quantitation of subunit isoform mRNAs in the major renal parenchymal zones. Transcripts for alpha 1, alpha 2, alpha 3, beta 1, and beta 2 subunit isoforms were detected by RT-PCR in microdissected glomeruli, proximal convoluted tubules, medullary thick ascending limbs of Henle, cortical and inner medullary collecting ducts. The truncated alpha 1 (alpha 1-T) isoform was also amplified from cortex, outer and inner medulla and isolated glomeruli, but it was not detected in these nephron segments. The DNA sequence of the renal alpha 1-T PCR product was identical to that of the cDNA previously cloned from aortic smooth muscle cells. RNA dot-blot analysis indicated that the alpha 1, alpha 2, and alpha 3 isoforms contributed approximately 70%, approximately 20%, and approximately 10%, respectively, of the total alpha isoform mRNA in each parenchymal zone. RNase protection assays determined that the beta 1 and beta 2 isoforms accounted for approximately 95% and approximately 5%, respectively, of the beta isoform mRNA in each zone. These data provide definitive evidence for the differential expression of mRNAs encoding all the alpha and beta isoforms in the renal parenchyma, and for the coexpression of these isoforms in the nephron segments examined. The results suggest the potential expression of up to eight different Na(+)-K(+)-ATPase isoenzymes in the kidney, and for multiple molecular levels of regulation of renal Na(+)-K(+)-ATPase expression. PMID- 7996787 TI - Mechanism of insulin-stimulated electrogenic sodium transport. AB - Studies were performed to determine the signal transduction mechanism involved in the onset of insulin stimulated electrogenic sodium transport (Ieq) in cultured A6 cells. Insulin stimulated Ieq at a threshold concentration of one nM and a half-maximum concentration of approximately 3 nM. The onset of action occurred within 10 seconds and the increase in Ieq was augmented by pretreatment with aldosterone, similar to the action of vasopressin. Insulin stimulated an increase in Ca2+i in a dose-dependent manner that involved release from intracellular stores. Hormone stimulated Ieq was dependent on increases in Ca2+i because pretreatment with 5, 5' dimethyl BAPTA/AM blocked the increase in sodium transport. Further studies with dihydroxyclorpromazine, trifluoperazine and genistein, inhibitors of PKC, Ca2+i dependent, calmodulin dependent kinases and tyrosine kinase, respectively, suggested that the action of insulin was dependent on activation of these kinases. In contrast, insulin stimulated Ieq was independent of changes in cAMP, because insulin did not increase the accumulation of cAMP, and inhibition of adenylate cyclase with 2', 5' dideoxyadenosine did not affect transport. These results suggest that insulin, as previously shown for aldosterone, activates apical membrane amiloride sensitive sodium channels by a calcium-dependent second messenger system. PMID- 7996788 TI - Glucocorticoid uncoupling of antiogensin II-dependent phospholipase C activation in rat vascular smooth muscle cells. AB - Vascular tone is maintained by both angiotensin II (Ang II) and glucocorticoids, but the effect of glucocorticoids on Ang II function in vascular smooth muscle cells (VSMC) is unclear. To determine the direct influence of glucocorticoids on VSMC Ang II receptor function, the effects of dexamethasone on Ang II receptor binding, Ang II-induced phospholipase C (PLC) activation, and Ang II-dependent cell growth were studied in cultured rat VSMC. Dexamethasone caused concentration and time-dependent increases in Ang II binding which were prevented by glucocorticoid receptor inhibition with RU 38486. Dexamethasone-induced enhancement of Ang II binding resulted from increased AT1 receptors, as indicated by Northern blot analysis and competitive binding assays. Despite causing increased Ang II receptor number, dexamethasone preincubation prevented Ang II induced PLC activation, as indicated by phosphatidylinositol 4,5-bisphosphate degradation and inositol trisphosphate formation. When PLC activity was directly measured in VSMC soluble and membrane fractions, Ang II receptor activation caused decreased soluble and increased membrane PLC activity, consistent with the interpretation that Ang II caused cytosol-to-membrane PLC translocation. The effect of Ang II on PLC translocation was prevented by dexamethasone preincubation. Finally, prolonged incubation with dexamethasone and Ang II had additive effects on VSMC hypertrophy. In conclusion, glucocorticoids directly altered Ang II function in VSMC by causing increased Ang II receptor number, Ang II receptor/PLC uncoupling, and enhanced Ang II-dependent hypertrophy. PMID- 7996790 TI - Captopril inhibits the agonist-induced increase of cytosolic free Ca2+ in glomerular mesangial cells. AB - To evaluate the underlying mechanism of the putative renal protective effects of angiotensin converting enzyme (ACE) inhibitors, the modulatory action of captopril on the angiotensin II (Ang II) and platelet-derived growth factor (PDGF)-induced increase of cytosolic free calcium concentration ([Ca2+]i) was investigated in cultured glomerular mesangial cells (MC) from spontaneously hypertensive rats from the Munster strain (SHR) and normotensive Wistar-Kyoto rats (WKY). Resting [Ca2+]i was not affected by captopril in MC from either SHR or WKY. Captopril inhibited the Ang II-induced [Ca2+]i increase in MC from both SHR and WKY in a dose-dependent and time-dependent fashion. The preincubation of MC with 1 mumol/liter captopril for 40 minutes significantly reduced the Ang II induced [Ca2+]i increase in SHR from 167 +/- 30 nmol/liter (N = 17) to 74 +/- 20 nmol/liter (N = 8, P < 0.05) and in WKY from 102 +/- 42 nmol/liter (N = 14) to 43 +/- 12 nmol/liter (N = 7, P < 0.05). After removal of external calcium there was no significant effect of captopril on the Ang II-induced [Ca2+]i increase. With the Mn2+ quenching technique, it was confirmed that captopril affects Ca2+ influx. Phospholipase C activity as estimated by diacylglycerol formation was not changed by captopril. The preincubation of MC with 1 mumol/liter captopril for 40 minutes significantly reduced the PDGF-induced [Ca2+]i increase in SHR from 166 +/-54 nmol/liter (N = 9) to 31 +/- 19 nmol/liter (N = 6, P < 0.01) and in WKY from 127 +/- 31 nmol/liter (N = 11) to 61 +/- 32 nmol/liter (N = 5, P < 0.05). Similarly captopril reduced the [Ca2+]i increase induced by endothelin and vasopressin. The results indicate that the actions of Ang II and PDGF on MC are modulated by captopril, probably resulting in the impairment of the calcium dependent contractile response of mesangial cells. PMID- 7996789 TI - Induction of heparin-binding epidermal growth factor-like growth factor mRNA by protein kinase C activators. AB - Heparin-binding epidermal growth factor-like growth factor (HB-EGF) is a potent smooth muscle cell mitogen of macrophage origin. To determine whether the HB-EGF gene is transcribed and regulated in mesangial cells, we measured HB-EGF mRNA levels in cultured rat mesangial cells by RNA blot analysis. A 2.5-kb HB-EGF mRNA was detected in unstimulated mesangial cells. The protein kinase C activator 12-O tetradecanoylphorbol 13-acetate (TPA) increased HB-EGF mRNA levels by 15-fold in mesangial cells, and this induction of HB-EGF mRNA by TPA was both time- and dose dependent. HB-EGF mRNA could also be stimulated by 10% fetal calf serum, ionomycin, thrombin, and endothelin-1. Staurosporine, a protein kinase C inhibitor, abolished the induction of HB-EGF mRNA by TPA and serum. To determine whether HB-EGF is mitogenic for mesangial cells, we transfected COS cells with HB EGF expression plasmids. Culture medium from COS cells transfected with these plasmids increased 3H-thymidine incorporation in mesangial cells in a dose dependent manner. To our knowledge, this is the first report that HB-EGF is expressed in renal cells. This inducible transcription of HB-EGF suggests that it may have an autocrine role in mesangial cell proliferation in kidney disease. PMID- 7996791 TI - Isoproterenol and 8-bromo-cyclic adenosine monophosphate stimulate the expression of the angiotensinogen gene in opossum kidney cells. AB - To investigate whether the expression of the renal angiotensinogen (ANG) gene is regulated by beta-adrenoceptors and the cAMP-dependent protein kinase A pathway, we introduced stably the fusion gene containing the 5'-flanking regulatory sequence of the ANG gene with a human growth hormone (hGH) gene as a reporter, pOGH (ANG N-1498/+18), into opossum kidney (OK) cells. We successfully obtained several stable transformants with a high expression of the pOGH (ANG N-1498/+18) fusion gene. One stable transformant (OK 27) that is able to maintain the expression of pOGH (ANG N-1498/+18) in culture for more than a year was used in the present study. The level of expression of the pOGH (ANG N-1498/+18) in OK 27 was evaluated by the amount of immunoreactive-hGH (IR-hGH) secreted into the culture medium. The addition of isoproterenol (10(-11) M to 10(-9) M) stimulated the expression of pOGH (ANG N-1498/+18) and increased the accumulation of intracellular cAMP. Higher concentrations of isoproterenol (that is, greater than 10(-9) M) had low or minimal effect. In contrast, the addition of 8-bromo-cAMP (8 Br-cAMP) and forskolin stimulated the expression of pOGH (ANG N-1498/+18) in a dose-dependent manner. The stimulatory effect of isoproterenol was blocked by the presence of propranolol, atenolol and ICI 118,551. The addition of ICI 118,551, however, was less effective than atenolol. Furthermore, the stimulatory effect of isoproterenol and 8-Br-cAMP on the expression of the pOGH (ANG N-1498/+18) was inhibited by the presence of Rp-cAMP (an inhibitor of cAMP-dependent protein kinase A I and II).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7996792 TI - Exogenous nitric oxide prevents endotoxin-induced glomerular thrombosis in rats. AB - Nitric oxide (NO) synthesized from L-arginine is an endogenous vasodilator and inhibitor of platelet adhesion and aggregation. Gram-negative lipopolysaccharide (LPS) can induce NO synthesis, which may mediate the pathophysiologic effects of endotoxemia. In addition, our previous studies suggested that LPS-induced NO may protect against thrombosis in rats. In the present study, male Sprague-Dawley rats given LPS (0.1 mg/kg) i.p. increased their urinary excretion of NO2 + NO3 (stable end-products of NO) by 4.3-fold. Rats given 10 micrograms/kg/hr i.v. of nitroglycerin (GTN), an exogenous NO donor, showed a similar increase. L-NAME, an inhibitor of NO synthesis, abrogated the increase in urinary NO2 + NO3 in LPS treated rats but not in rats given GTN. Glomerular thrombosis developed in rats given LPS + L-NAME (thrombosis score = 3.02 +/- 0.4), while those given LPS + L NAME + GTN were largely protected (thrombosis score = 1.37 +/- 0.5, P < 0.05). Atrial natriuretic peptide (ANP), an NO-independent vasodilator, neither increased urinary NO2 + NO3 nor prevented glomerular thrombosis (thrombosis score = 2.68 +/- 0.5, NS). Hydralazine, another vasodilator without effects on NO or platelets, also failed to prevent glomerular thrombosis in rats given LPS + L NAME. We conclude that in endotoxemia, the antithrombogenic properties of endogenously synthesized NO are important in preventing alomerular thrombosis. The exogenously NO donor, GTN, can substitute for the antithrombogenic effect of endogenous NO. Clinically, administration of NO synthesis inhibitors to treat endotoxic shock may need to be combined with concomitant administration of exogenous NO donors to prevent microvascular thrombosis. PMID- 7996793 TI - Characterization of C-type natriuretic peptide receptors in human mesangial cells. AB - Our aim was to examine whether the human glomerulus was a target for C-type natriuretic peptide (CNP) and how A, B and C receptors of natriuretic peptides (ANPR-A, ANPR-B, ANPR-C) were distributed in glomerular mesangial and epithelial cells. CNP stimulated cyclic GMP production in cultured human mesangial and epithelial cells with similar threshold concentrations (1 nM) and maximum effects (basal value x 30 at 1 microM). In contrast, atrial natriuretic peptide (ANP) was only stimulatory in epithelial cells. [125I] CNP bound specifically to mesangial cells with a Kd of 0.47 nM and Bmax of 42 fmol/mg. Equilibrium of binding was obtained after four to five hours at +4 degrees C and nonspecific binding represented 10 to 20% of total binding. HS142-1 (100 micrograms/ml), a specific inhibitor of ANPR-A and ANPR-B, suppressed 90% of CNP-dependent cyclic GMP production whereas it had little effect on [125I]-CNP binding, suggesting that C receptors were largely predominant in mesangial cells. No biological effect of CNP on mesangial cells, including change in basal or angiotensin II-induced contractility and inhibition of basal or serum-dependent proliferation, could be demonstrated. Similar results were obtained with 8-bromo-cyclic GMP and sodium nitroprusside. Intraglomerular localization of ANPR-A, ANPR-B and ANPR-C mRNA was studied using reverse transcriptase-polymerase chain reaction with amplification of their corresponding cDNA by different primers. Amplification products were identified on gel electrophoresis by their predicted sizes and sequencing. ANPR A, ANPR-B and ANPR-C mRNA were present in epithelial cells whereas only ANPR-B and ANPR-C mRNA were detected in mesangial cells.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7996794 TI - Increased platelet-derived growth factor in the kidneys of cyclosporin-treated rats. AB - We have examined the histological changes and the distribution of immunoreactive platelet-derived growth factor (PDGF) in the kidneys of Sprague-Dawley rats injected with cyclosporin A (CsA, 25 mg/kg/day). Control rats were injected with the olive oil vehicle alone. Groups of rats were killed after 1, 2, 3, 4 weeks of injection and 8 weeks after a 4 week period of injection. Additional controls included groups of rats injected with different doses of CsA and a group of rats subjected to chronic renal ischemia by partial of the aorta. CsA-treated rats gained weight more slowly than olive oil-treated controls (45%, P < 0.05). In rats injected with CsA, a significant increase in serum creatinine concentration (64 +/- 2 mumol/liter vs. 39 +/- 1 mumol/liter, P < 0.01) and a reduction in creatinine clearance rates (0.23 +/- 0.07 ml/min/100 g body wt vs. 0.43 +/- 0.07 ml/min/100 g body wt, P < 0.01) occurred after 3 weeks. After 1 week of CsA treatment, segments of the walls of some afferent and intralobular arterioles were thickened and stained strongly by the periodic acid Schiff (PAS) procedure. Immunostainable PDGF-BB and PDGF-AB were detected within short segments of the afferent and intralobular arterioles of the kidneys of CsA-treated rats and in the kidneys subjected to renal ischemia but not in tissue from other control animals. No PAS staining or immunostaining was evident in CsA treated kidneys eight weeks after the discontinuation of treatment. We conclude that CsA-induced ischemia results in increased accumulation of PDGF in the walls of renal arterioles. PMID- 7996795 TI - Three-dimensional analysis of the spine in autopsy cases with renal osteodystrophy. AB - The spinal column was removed from nine autopsy cases with chronic maintenance dialysis and sectioned in the sagittal plane to a thickness of 1 millimeter using a surface-stained block grinding technique. A combination of two- and three dimensional analysis included an evaluation of the spine deformity index (SDI), the bone volume (BV/TV), the trabecular interconnection (TBPf), the trabecular thickness (Tb.Th), the trabecular number (Tb.N) as well as a qualitative investigation of the structure of cancellous bone. The control group consisted of 26 autopsy cases with intact skeletons. An iliac crest biopsy made a direct comparison of the diagnostic biopsy location and the spinal column possible. The SDI showed vertebral fractures in renal osteodystrophy (ROD) of types I and II, in spite of a trabecular bone volume within normal limits. The trabecular bone volume showed mean values and a distribution throughout the spinal column familiar in the skeletally-intact control group. Those cases with a longer history of hemodialysis showed higher BV/TV values regardless of age and sex. A trabecular volume within normal limits did not mean physiological trabecular interconnection. Perforations were commonly observed with ROD. Classical, hidden and tunnelling perforations were distinguished. Microcallus formations were frequently seen in the periphery of vertebrae at rod nodes, rods and plate intersections. Three-dimensional analysis in ROD shows a greater alteration in architecture than can be assumed from the two-dimensional histological sections. PMID- 7996796 TI - Presence of C-type natriuretic peptide in human kidney and urine. AB - The current study was undertaken to investigate the presence of CNP immunoreactivity in both human kidney and urine. Immunohistochemical staining with an indirect immunoperoxidase method utilizing an antibody which is 100% cross-reactive to both CNP-53 and CNP-22 was performed on five human kidney specimens (three biopsies of normal cadaveric donor kidneys and two of normal autopsy specimens). CNP immunoreactivity was positive in proximal, distal and medullary collecting duct tubular cells in a cytoplasmic and granular staining pattern. CNP immunoreactivity was also determined in the urine of five healthy volunteers utilizing a sensitive and specific double-antibody radioimmunoassay with a mean concentration of 10.8 +/- 1.0 pg/ml. With the utilization of high pressure liquid chromatography, this immunoreactivity proved to be consistent with both the low molecular weight form, CNP-22, as well as the high molecular weight form, CNP-53. Urinary excretion of CNP was also measured in normal subjects (N = 5) and in patients with congestive heart failure (CHF, N = 6). CHF patients excreted over three times more CNP than normals (27.2 +/- 2.8 vs. 8.7 +/ 0.81 pg/min, P < 0.004) despite no difference between the two groups in plasma CNP concentrations (6.97 +/- 0.28 vs. 8.08 +/- 1.52 pg/ml, P = NS). This study demonstrates for the first time the presence of CNP immunoreactivity in human kidney and suggests that renal tubular cells may be an additional non-vascular site of synthesis for this cardiorenal acting peptide. This study also demonstrates an increase in urinary CNP excretion in congestive heart failure. PMID- 7996797 TI - Renal TGF-beta regulation in spontaneously diabetic NOD mice with correlations in mesangial cells. AB - Diabetic nephropathy is characterized by excessive glomerular matrix accumulation, basement membrane thickening and sclerosis. Although it is clear that systemic metabolic disturbances precipitate such renal changes, the signals and pathways involved in this process are not fully elucidated. Recent evidence suggests that growth factors/cytokines are intimately involved in the pathogenesis of diabetic nephropathy. Because of its prosclerotic properties, transforming growth factor-beta (TGF-beta) is a prime candidate mediator of diabetic nephrosclerosis. We examined perfused kidney tissues isolated from spontaneously diabetic, non-obese diabetic mice (NOD) for TGF-beta content. By using murine isotype specific TGF-beta probes, we demonstrate that within 5 to 10 days of hyperglycuria renal TGF-beta 2 mRNA and protein content increases. By immunohistochemical analysis, de novo TGF-beta immunoreactivity was detected within both glomeruli and the interstitium. In order to determine the signals involved in promoting kidney TGF-beta content in vivo, TGF-beta regulation was examined in renal mesangial cells in vitro. Murine mesangial cells stimulated with glycosylated protein secrete bioactive TGF-beta and demonstrate a disproportionate increase in the steady state levels of TGF-beta 2 mRNA. These data suggest that a major early renal response in NOD mice to hyperglycemia or to glycosylated proteins is characterized by increases in TGF-beta. PMID- 7996798 TI - bFGF and its low affinity receptors in the pathogenesis of HIV-associated nephropathy in transgenic mice. AB - HIV-associated nephropathy is characterized by extensive tubulointerstitial disease with epithelial cell injury, microcystic proliferation, and tubular regeneration with glomerulosclerosis. To explore the role of bFGF as a mediator of HIV-induced interstitial disease, we utilized an HIV transgenic mouse model that manifests clinical and histological features observed in patients. In transgenic mice, simultaneous renal epithelial cell proliferation and injury were detected in vivo. In areas of microcystic proliferation, immunoreactive bFGF colocalized with extracellular matrix. Kidneys from transgenic mice had increased bFGF low affinity binding sites, particularly in the renal interstitium. In vitro, transgenic renal tubular epithelial cells proliferated more rapidly and generated tubular structures spontaneously, in marked contrast to nontransgenic renal cells where these pathologic features could be mimicked by exogenous bFGF. These studies suggest that renal bFGF and its receptors play an important role in the pathogenesis of HIV-associated nephropathy. PMID- 7996799 TI - Role of nitric oxide in renal hemodynamic abnormalities of cyclosporin nephrotoxicity. AB - To evaluate the participation of nitric oxide (NO) in chronic cyclosporin A (CsA) nephrotoxicity, the glomerular hemodynamic response to NO inhibition with N-nitro L-arginine-methyl-ester (NAME) and stimulation of NO production with L-arginine was studied in uninephrectomized rats. Chronic CsA administration produced renal vasoconstriction, characterized by increased afferent (AR) and efferent (ER) resistances, decrease of glomerular plasma flow (QA) and ultrafiltration coefficient (Kf) that resulted in a 53% fall of single-nephron glomerular filtration rate (SNGFR). NAME infusion in vehicle group (V) elevated mean arterial pressure (MAP), AR and ER, reduced qA and Kf, and increased glomerular capillary pressure (PGC), resulting in a 28.9% fall of SNGFR. In the CsA group, NAME also increased MAP, but renal vasoconstriction was more intense; a greater rise of AR lowered PGC (P < 0.05 vs. V) further decreasing SNGFR by 38.9%. In control rats, L-arginine infusion induced a vasodilatory response of AR and ER, and elevation of QA and Kf, which resulted in a 72.6% increase in SNGFR. In the CsA group, greater vasodilation was observed and SNGFR rose by 114.9%. NO2-/NO3- urinary excretion was similar in CsA and V groups, and it was not modified by NAME in either group, but it increased five- to sixfold during L-arginine infusion in both groups. In conclusion, in CsA nephrotoxicity NO production seems to be normal and the ability of the renal endothelium to produce NO is maintained. Therefore renal vasoconstriction associated with CsA is not mediated by NO deficiency, although NO appears to attenuate it. PMID- 7996800 TI - Urinary kallikrein and salt sensitivity in essential hypertensive males. AB - A strong influence of urinary kallikrein excretion on the salt sensitivity of blood pressure has been recently suggested in normotensive patients. To evaluate the relationship between kallikrein and salt sensitivity in essential hypertension, active kallikrein excretion, plasma renin activity, atrial natriuretic peptide and aldosterone levels were evaluated in 37 male hypertensives (mean age 43.3 +/- 4.7 years) after two weeks on a normal NaCl diet (120 mmol NaCl per day). After kallikrein determination, salt sensitivity was assessed in a randomized cross-over double-blind fashion by evaluating the blood pressure response to a high (240 mmol NaCl per day for two weeks) and a low (40 mmol NaCl per day for 2 weeks) NaCl intake. Blood pressure changes were evaluated considering as baseline blood pressure the measurement taken at the end of the 2 weeks under normal NaCl intake. Patients were classified as salt sensitive when a diastolic blood pressure change of 10 mm Hg or more occurred after both periods of low and high NaCl intake. At the end of the assessment of salt sensitivity, 19 hypertensive patients (mean age 43.0 +/- 4.6 years) were resistant. The urinary excretion of active kallikrein was significantly lower (P < 0.0001) in salt sensitive (0.51 +/- 0.36 U/24 hr) than in salt resistant patients (1.28 +/- 0.48 U/24 hr). Also, plasma atrial natriuretic peptide levels were higher in salt sensitive than in salt resistant hypertensives (P < 0.02), and a significant correlation between urinary kallikrein and plasma atrial natriuretic peptide was demonstrated in salt sensitive hypertensives (r = -0.691, P < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7996801 TI - Urea kinetic modeling: an in vitro and in vivo comparative study. AB - The urea kinetic model (UK) and the direct dialysis quantification method based on dialysate collection (DDQ) were used to determine the urea distribution volume (V) identified with the total body water and the urea generation rate (G) for different dialysis times, both in vivo during short hemodialysis (N = 20) and in vitro using an experimental single-pool urea system (N = 10). Both UK and DDQ allowed a satisfactory in vitro estimation of V and G for all dialysis times. On the other hand in vivo V and G estimations by both methods showed an increase of more than 50% between the determinations performed after 30 minutes of dialysis and at the end of dialysis. Our theoretical analysis shows that the in vivo changes of V are compatible with those expected for a two-compartment system in which one compartment is cleared faster than the other. Furthermore, given that urea is allowed to equilibrate in the body at the end of dialysis, DDQ permits an accurate estimate of V, G and PCR even for short hemodialysis, which UK does not. PMID- 7996802 TI - Increased cardiovascular risk factors and features of endothelial activation and dysfunction in dialyzed uremic patients. AB - Due to the incidence of symptomatic atherosclerosis in uremic patients, hemostasis-derived cardiovascular risk factors, basal plasma concentrations of some endothelial-derived glycoproteins and desmopressin-induced variations of endothelial-derived proteins were studied in 22 uremic patients on prolonged maintenance hemodialysis with no cardiovascular antecedent. Compared to control subjects, patients had increased predialysis hemostasis-related cardiovascular risk factors: high fibrinogen, proconvertin, and type 1 plasminogen activator inhibitor plasma concentrations; low albumin values; generally low antithrombin III values but sometimes high. They had high predialysis plasma concentrations of endothelium-derived glycoproteins: von Willebrand factor, tissue-type plasminogen activator and urokinase-type plasminogen activator, which are secreted by endothelial cells, but also soluble thrombomodulin, a marker of endothelial cell injury. The desmopressin-induced release of tissue-type plasminogen activator and of von Willebrand factor were lower than in controls. High fibrinogen, type 1 plasminogen activator inhibitor and low albumin plasma concentrations may be linked to repeated acute phase reactions associated with hemodialysis. Data concerning endothelium-related proteins are concordant with the co-existence of a chronic in vivo endothelial activation and endothelial injury in uremia. This could be linked to the initiation and progression of atherosclerosis. PMID- 7996803 TI - Hemodialysis-associated protein catabolism with and without glucose in the dialysis fluid. AB - The effects of hemodialysis on protein and energy metabolism were studied in eight hemodialysis patients. The leg exchange of amino acids (AA) was measured during hemodialysis using a dialysis fluid with 10 mmol/liter glucose (GD) or without glucose (GFD). Arterial AA concentrations decreased by about 30% in GD and GFD. During dialysis, similar increases in the efflux of AA from leg tissues (mainly muscle) were observed in GD and GFD (basal 105 +/- 104, vs. 71 +/- 62 nmol/min/100 g tissue; dialysis 295 +/- 46 vs. 289 +/- 60 nmol/min/100 g tissue). The efflux of AA remained largely unchanged at one hour after the end of GD and GFD. Losses of AA to the dialysate were similar during GD (8.3 +/- 0.9 g) and GFD (7.9 +/- 0.4; NS). GFD resulted in a loss of 26 g of glucose whereas 30 of glucose was absorbed during GD. The amount of urea removed by dialysis and the post-dialysis increase in plasma urea were similar in GD and GFD. In conclusion, the addition of glucose to the dialysis fluid may help the energy balance, but it does not appear to reduce the negative effects of hemodialysis on protein metabolism. PMID- 7996804 TI - Amino acid and albumin losses during hemodialysis. AB - Protein and calorie malnutrition are prevalent in chronic hemodialysis (HD) patients and has been linked to increased mortality and morbidity in this patient population. Concern has been raised that the open pore structure of high flux membranes may induce the loss of more amino acids (AA) compared to low flux membranes. To address this issue, we prospectively analyzed pre- and post-HD plasma AA profiles with three different membranes in nine patients. Simultaneously, we measured dialysate AA losses during HD. The membranes studied were: cellulosic (cuprophane-CU), low flux polymethylmethacrylate (LF-PMMA), and high flux polysulfone (HF-PS) during their first use. Our results show that pre HD plasma AA profiles were abnormal compared to controls and decreased significantly during HD with all dialyzers. The use of HF-PS membranes resulted in significantly more AA losses into the dialysate when compared to LF-PMMA membranes (mean +/- SD; 8.0 +/- 2.8 g/dialysis for HF-PS, 6.1 +/- 1.5 g/dialysis for LF-PMMA, p < 0.05, and 7.2 +/- 2.6 g/dialysis for CU membranes, P = NS). When adjusted for surface area and blood flow, AA losses were not different between any of the dialyzers. We also measured dialysate AA losses during the sixth reuse of the HF-PS membrane. Losses of total AA increased by 50% during the sixth reuse of HF-PS membrane compared to its first use. In addition, albumin was detected in the dialysate during the sixth reuse of HF-PS membrane. We therefore measured albumin losses in all patients dialyzed with HF-PS membranes as a function of reuse.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7996805 TI - Osteocalcin: a non-invasive index of metabolic bone disease in patients treated by CAPD. AB - Serum osteocalcin has been found to correlate with bone formation. However, present literature gives only limited data on osteocalcin and bone histomorphometry in patients undergoing peritoneal dialysis. This study assessed serum osteocalcin, dialysate osteocalcin, peritoneal clearance of osteocalcin (Clp-osteocalcin) and mass transfer of osteocalcin (MTp-osteocalcin), and evaluated relationships between these values and bone histomorphometry. Eighteen patients were treated by continuous ambulatory peritoneal dialysis (CAPD). Bone biopsies, serum and dialysate osteocalcin, serum levels of parathyroid hormone, alkaline phosphatase, aluminum, phosphate, Ca2+ and vitamin D3 metabolites were measured at the start and in 10 of the patients a year later. Serum osteocalcin was found to be elevated. Osteocalcin was detected in the dialysate resulting in significant values of Clp-osteocalcin and MTp-osteocalcin. Serum and dialysate levels of osteocalcin correlated significantly (r = 0.66, P < 0.001) and like MTp osteocalcin with serum levels of alkaline phosphatase and PTH. Histomorphometry showed that osteitis fibrosa was the predominant bone disease detected. Serum concentration of osteocalcin correlated with osteoid thickness, eroded and osteoclast surfaces, aluminum staining, and some of the bone dynamic parameters. Dialysate osteocalcin, MTp-osteocalcin, PTH and alkaline phosphatase correlated with practically the same histomorphometric parameters as serum osteocalcin. No correlations were seen between Clp-osteocalcin and any histomorphometric parameters. Serum osteocalcin was elevated above the normal range, and significant positive correlations between serum osteocalcin and bone formation parameters were found. Serum osteocalcin correlated with almost the same histomorphometric parameters as PTH. Thus, serum levels of PTH and osteocalcin gave additional information to one another as non-invasive parameters in this group of patients.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7996806 TI - Calcium oxalate nephrolithiasis, a free or fixed particle disease. AB - The chances of stone formation occurring through a free particle mechanism were calculated using the approach of Finlayson and Reid [1]. For these calculations we used new data on nephron dimensions, supersaturation and crystal growth rates in urine, and also incorporated the size increasing effect of crystal agglomeration. The calculations were performed assuming different levels of oxalate excretion, simulating the diurnal variation and acute hyperoxaluria following a dietary load. In addition urinary flow conditions were varied according to changes in daily urinary volume. It is shown that during the normal transit time of urine through the nephron, particles can obtain a size big enough to be retained in the nephron. This is mainly due to the size-increasing effect of the agglomeration process. The precipitable amount of oxalate present is not limiting for the maximum attainable particle size. However, acute increases in oxalate excretion do pose a risk because supersaturation is reached earlier in the nephron and consequently the crystal particles are allowed more time to increase in size. In conclusion, the present calculations demonstrate that during the normal transit time through the kidney, crystalline particles can be formed which are large enough to be retained because of their size and thus form the nidus of a stone. The highest risk is encountered at the end of those collecting ducts where crystals formed in nephrons with a long loop of Henle meet and agglomerate. PMID- 7996807 TI - Evidence for abnormal calcium homeostasis in patients with adynamic bone disease. AB - To investigate whether the derangements in calcium kinetics in patients with renal osteodystrophy are similar in the various histologic forms of this metabolic bone disease, 43 patients on chronic maintenance dialysis underwent calcium kinetic studies using the double isotope technique, iliac crest bone biopsies for mineralized bone histology and histomorphometry and determinations of serum indices of calcium and bone metabolism. Intestinal calcium absorption was not different among the three histologic groups. However, women exhibited lower calcium absorption in each histologic form (P < 0.01). Patients with predominant hyperparathyroid bone disease showed plasma calcium efflux, calcium accretion rate and calcium retention markedly above normal values. Patients with low turnover bone disease exhibited a normal or slightly decreased plasma calcium efflux and calcium accretion rate together with a disproportionately low calcium retention. Patients with mixed uremic osteodystrophy presented with a calcium kinetic profile intermediary to the two other forms. Good relationships existed between plasma calcium efflux, calcium accretion rate, calcium retention and histomorphometric parameters of bone turnover as well as serum levels of parathyroid hormone. However, no serum parameter could indicate with certainty the underlying bone disease. These findings demonstrate that adynamic bone disease does not merely represent an academic finding but is characterized by a very low bone capacity to buffer calcium and inability to handle an extra calcium load. This is particularly relevant for the daily care of end-stage renal failure patients presently receiving higher than ever amounts of vitamin D and calcium salts. PMID- 7996808 TI - Increased mRNA encoding for transforming factor-beta in CD4+ cells from patients with IgA nephropathy. AB - IgA nephropathy (IgAN) is a mesangial proliferative glomerulonephritis characterized by predominant mesangial IgA deposits. Recently, transforming growth factor-beta (TGF-beta) is shown to exert widespread effects on extracellular matrix by enhancing its accumulation. In an experimental model of acute mesangial glomerulonephritis TGF-beta appeared to be involved in the process of glomerulosclerosis, and treatment with antagonists of TGF-beta prevented the development of glomerulosclerosis. We examined the TGF-beta mRNA expression by mitogen activated CD4+ T cells from 31 patients with IgAN, 25 healthy controls and 10 patients with minimal change nephropathy (MCN) or focal glomerulonephritis (FGN) who were comparable in age and sex. The cytokine gene was analyzed with reverse transcription followed by polymerase chain reaction and was semiquantitated by normalizing the differences occurring during reverse transcription and polymerase chain reaction using a housekeeping gene, beta actin. CD4+ T cells from IgA nephritic patients expressed a higher level of TGF beta mRNA than that of healthy controls or that of MCN/FGN [TGF-beta/actin ratio 1.11 (median), range 0.24 to 3.87 vs. 0.88, range 0.2 to 3.83, P = 0.0157 and 0.36 range 0.09 to 1.6, P = 0.006]. When the biopsies were classified into three grades according to the severity of glomerular and interstitial pathology, there were highly significant differences between the TGF-beta mRNA in CD4+ T cells from the three groups of IgA nephritic patients (grade 1, 0.52, range 0.24 to 0.79; grade 2, 1.2, range 0.5 to 3.33; grade 3, 2.17, range 1.45 to 3.87].(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7996809 TI - Autoantibodies against oxidatively-modified LDL in uremic patients undergoing dialysis. AB - Target-specific oxidation processes in LDL generate molecular epitopes that are more atherogenic than the native forms and are able to elicit an immunological reaction leading to the formation of anti-oxLDL autoantibodies (oxLDL-Ab) that may participate in the overall process of atherogenesis. Thus, the detection of oxLDLAb, in addition to mirroring the occurrence of in vivo LDL oxidation, will give valuable information on the occurrence of this immune response. Plasma oxLDLAb (IgG and IgM) were measured in 72 control subjects (CS) and in 80 patients with chronic renal failure (CRF), undergoing repetitive hemodialysis (N = 56) or peritoneal dialysis (N = 24), with an ELISA method using native LDL, CuSO4-oxidized LDL (oxLDL) or malondialdehyde-derivatized LDL (MDA-LDL) as antigens. To monitor cross reactivity of the antibodies detected with other oxidatively-modified proteins, human serum albumin (HSA) and MDA-derivatized HSA (MDA-HSA) were also employed as antigens. The antibody titer was calculated as the ratio of antibodies against modified versus native proteins. CRF patients had an antibody ratio significantly higher than CS as concerning anti-oxLDL IgG (1.39 +/- 0.36 vs. 1.05 +/- 0.3, P < 0.05) and IgM (2.15 +/- 0.75 vs. 1.43 +/- 0.43, P < 0.01), and anti-MDA-LDL IgG (3.05 +/- 0.74 vs. 2.04 +/- 0.42, P < 0.01) and IgM (5.55 +/- 1.79 vs. 2.9 +/- 0.85, P < 0.01). The anti-MDA-HSA antibody titer was also higher in CRF patients than in CS (2.49 +/- 0.5 vs. 1.46 +/- 0.39, P < 0.01 for IgG and 2.80 +/- 1.03 vs. 1.26 +/- 0.43, P < 0.01 for IgM).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7996810 TI - Identification and independent regulation of human mesangial cell metalloproteinases. AB - Mesangial cells are known to secrete metalloproteinases that are capable of degrading the constituents of the GBM, and hence are potentially involved not only in the regular maintenance of the ECM components in the glomerulus, but also of contributing to any damage to these components that occurs in disease states. In this report we positively identify by Northern blotting the neutral proteinase that is constitutively secreted by the human mesangial cell (HMC) as gelatinase A (MMP2). Stimulation of HMC gelatinase by IL-1 beta or PMA causes an increase in the total amount of gelatinolytic activity secreted. On examination, however, this increased activity is shown, both by immunoreactivity and by PCR to be due to the induction of the higher molecular weight form of gelatinase, gelatinase B (MMP9), while the amount of gelatinase A remained unaffected. In addition antigen and messenger RNA have been identified for both the specific inhibitors of metalloproteinases TIMP-1 and TIMP-2. The appearance of the larger inducible gelatinase with similar substrate specificity implies that the regular turnover of matrix components may be due to the constitutively released gelatinase A while in pathological situations the inducible gelatinase B becomes predominant. The synthesis and secretion of TIMP-1 and TIMP-2 indicates that the mesangial cell is capable of controlling the activity of its own secreted enzymes. PMID- 7996811 TI - Demographic and geographic variability of kidney stones in the United States. AB - To characterize demographic and regional variation in kidney stone prevalence in the U.S. we studied two nationwide cross-sectional surveys that included data on self-reported, physician-diagnosed kidney stones, supplementing published data on hospitalizations for stones. The larger study, Cancer Prevention Study II (CPS II), included 1,185,124 men and women, age > or = 30, recruited nationally in 1982, and provides state-specific prevalence estimates. The National Health and Nutrition Examination Survey (NHANES II) was a national probability sample of 25,286 U.S. adults interviewed between 1976 and 1980. Kidney stone prevalence increased with age until age 70, then declined and was higher in men than women and in whites than blacks. Prevalence among Hispanic and Asian men was intermediate between that of whites and blacks. There was a strong, statistically significant regional variability in stone prevalence among U.S. whites. The age adjusted prevalence increased from north to south, and from west to east. The contrast in state-specific prevalence was greatest between men in North Carolina (prevalence = 14.9; 95% confidence interval = 14.2 to 15.7) and North Dakota (5.6; 4.7 to 6.4), and between women in South Carolina (6.4; 5.8 to 6.9) and South Dakota (2.4; 1.9 to 2.9). The marked variations in kidney stone prevalence by age, gender, race, and geographic location may provide clues to their etiology and prevention. PMID- 7996812 TI - Human peritoneal mesothelial cell prostaglandin synthesis: induction of cyclooxygenase mRNA by peritoneal macrophage-derived cytokines. AB - Increasing evidence suggests that the mesothelial cell contributes to the control of inflammation in both the normal and inflamed peritoneal cavity. The present study examines the regulation of prostaglandin production by human peritoneal mesothelial cells (HPMC) following stimulation with peritoneal macrophage conditioned medium and the cytokines interleukin-1 beta (IL-1 beta) and tumor necrosis factor-alpha (TNF-alpha). IL-1 beta and TNF-alpha stimulated significant release of prostaglandin above background levels in a time and dose dependent manner. Stimulation of HPMC with IL-1 beta (500 pg/ml) or TNF-alpha (100 pg/ml) for 24 hours resulted in the release of 24.5 +/- 4.3 (N = 11) (z = 3.40, P < 0.001 vs. control) and 19.4 +/- 4.5 (N = 10; z = 3.29, P < 0.001 vs. control) pg 6-keto-PGF1 a/micrograms cellular protein, respectively. Pretreatment of HPMC with dexamethasone (10(-6) to 10(-9) M) inhibited both constitutive and cytokine stimulated prostaglandin synthesis in a dose dependent manner. Both PMo-CM and PMo-S.epiCM stimulated 6-keto-PGF1 alpha and PGE2 synthesis by HPMC in a time and dose dependent manner (PMo-S.epiCM >> PMo-CM). Co-incubation of HPMC with PMo S.epiCM in the presence of anti-IL-1 beta and/or anti-TNF-alpha antibody, interleukin-1 receptor antagonist or soluble TNF receptor (TNF p75) significantly reduced the capacity of these supernatants to stimulate prostaglandin synthesis. Exposure of HPMC to cytokines or PMo-S.epiCM resulted in the time dependent increase in the levels of both Cox-1 and Cox-2 mRNA as assessed by RT/PCR analysis with the greatest increase being seen for Cox-2. These data demonstrate specific stimulation of eicosanoid metabolism in HPMC by peritoneal macrophage derived cytokines, indicating the possible importance of these mediators in the activation of intraperitoneal prostaglandin synthesis. HPMC prostaglandins might act as important pro/anti-inflammatory mediators contributing to a cytokine network in the peritoneal cavity during CAPD peritonitis. PMID- 7996813 TI - Lipids and the kidney. PMID- 7996814 TI - [Hermann von Helmholtz (1821-1894). On the 100th anniversary of his death]. AB - In Helmholtz's judgement it was a favourable fate to have been thrown under medical students and into medicine with a sense of geometrics and with knowledge of physics. The result of this favourable combination was the invention of the ophthalmoscope and the Handbook of Physiologic Optics. Those were the foundations of all physiological aspects of ophthalmology, which were taken up and completed by A. v. Graefe and his colleagues. The ophthalmoscope was invented on the occasion of his university-courses, when Helmholtz tried to explain the theory of the red reflex of the pupil. Stimulated by Helmholtz in the following year Ruete developed the method of indirect ophthalmoscopy. This method at once was simplified again by Helmholtz in an extraordinary way. These two publications by Helmholtz contain all further developments involved with the ophthalmoscopy as an anticipation. The Handbook of Physiologic Optics is the first encyclopedic monography of this topic. Many new inventions are extremely valuable for the practical requirements of ophthalmologists. The first chapter about dioptrics contains the description of the Ophthalmometer, a new instrument to measure the astigmatism. In the chapter about visual sensations a clear survey about light- and colour sense is given. The colour deficiencies which were found during the decades before are introduced as the most important arguments for the three component-theory of human colour vision. The prototype of a telestereoscope is demonstrated in the third chapter about visual perception.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7996815 TI - [Treatment of optic neuritis with corticosteroids. Discussion at the 10th Meeting of the International Neuro-ophthalmological Society (Freiburg 5 to 9 June 1994)]. PMID- 7996817 TI - [Video refraction measurement in the first year of life]. AB - BACKGROUND: 426 children were examined, using the isotropic photorefraction method (Atkinson et al. 1981). The aim of this study was to analyze whether the frequency of convergent strabismus and/or amblyopia would increase, particularly in cases of high ametropia, and whether the early prescription of spectacles would be beneficial. The preliminary results of this study are presented here. MATERIALS AND METHODS: 426 children aged between 5 and 12 months were examined. Family history, particularly involving strabismus, ametropia and amblyopia, was ascertained and taken into consideration. RESULTS: Spherical refraction: 92% of the children were emmetropic or slightly hyperopic (< or = +2.5 D). 3.4% were hyperopic (> +2.5 D spherical equivalent) and 4.6% were myopic (0.9 > or = -2.0 D). Astigmatism: 85% had no or mild (< or = 1.5 D) astigmatism. Values greater than 3.5 D were rarely seen. Anisometropia: 67% of the children had no side difference and only 2.4% had anisometropia with values greater than 1.5 D. Family history/orthoptic findings: 2.6% of the examined population had strabismus. In 12.2% of all the cases one or more first degree relatives had strabismus. Hyperopia and strabismus were found more frequently in this latter group, namely hyperopia (> +2.5 D spherical equivalent) in 13.6% and strabismus in 11.5%. CONCLUSIONS: Refractive errors greater than 2.5 D were seldom seen in this study, and yet were more frequently detected in families with a history of strabismus. In our opinion, isotropic photorefraction is a method most suitable to screening these especially high-risk groups. PMID- 7996818 TI - [Clinical study of the effectiveness of a new preservative-free polyvidon preparation in therapy of dry-eye disorders]. AB - BACKGROUND: Diseases of the ocular surface very frequently seen are related to irregularities of wetting. Patients often have complaints and feeling of ill health, although under symptomatic therapy. Tolerability of the tear substitutes plays a key role in these cases. It is improved with unpreserved medication. METHOD: 59 patients with 'dry eye condition' of various etiology were enrolled in an open multicentre study and treated 8 weeks with a new preservative-free tear substitute. All patients had a history of previous ineffective treatment with artificial tears. The product was formulated with polyvidone and electrolytes in a composition which resembles natural tears. The therapeutic effect was evaluated by ratings of patients' self assessment of their complaints, tear film break up time (BUT), Schirmer I test, visual acuity, biomicroscopic examination and physicians' assessment. RESULTS: Based on the key criteria patients's self assessment and BUT, the new agent (Oculotect fluid sine) improved symptoms and reduced discomfort significantly compared with the previous treatment (paired t test, two-sided, level of significance p < or = 0.05). The improved condition was confirmed by the other findings taken. CONCLUSION: In 4/5 of patients, as typically met in ophthalmologists' offices, whose complaints were insufficiently relieved by previously applied tear substitutes, treatment with the new preservative-free product resulted in a distinct improvement of their condition. The lack of preservatives contributed to better tolerability and acceptance of tear substitution. PMID- 7996816 TI - [How accurate is video refraction measurement in infants in comparison with skiascopy? How much do the values change within a half a year?]. AB - BACKGROUND: Isotropic photorefraction (Atkinson et al., 1981) is a method used to screen the refraction in infants. The aim of this study is to analyze its limitations as a measuring instrument. MATERIALS AND METHODS: 215 children aged between 5 and 12 months were examined in cycloplegia. The results were subsequently compared (1) to the results of streak retinoscopy also performed at the same time and (2) to photorefraction performed a second time, 6 months later (with 145 children). RESULTS: Spherical refraction: The mean spherical values differed by 0.70 dpt through photorefraction methods, compared to retinoscopy. The standard deviation (SD) was 0.67 dpt. The values of the photorefraction differed therefore in 95% of the children within a range of 2.7 dpt (or +/- 2 SD). Compared to the second photorefractive measurement 6 months later, the average refraction showed a small myopic shift (-0.45 dpt). Astigmatism: The errors of measurement were more pronounced here. Extreme differences of up to 9 dpt were found in single cases. The mean difference, compared to retinoscopy, was 0.73 dpt. The standard deviation (SD) was 0.90 dpt. In 95% of the children, the values of photo-refraction differed therefore by a range of 3.6 dpt (or +/- 2 SD). Compared to the second photorefractive measurement 6 months later, the average refraction showed a mean change of 0.73 dpt. CONCLUSIONS: Our photorefractive measurements showed errors in the range of 1-2 dpt for the spherical refraction, and in the range of 2-3 dpt for astigmatism. In 5% of the children examined, even greater aberrations were found. As long as the aim of photorefraction is restricted to disclosing high refractive errors, this method is judged suitable for the refractive screening of infants. For more precise refraction, and for the prescription of spectacles, we believe that is should be supplemented by a second examination technique, such as retinoscopy or automated refractometry. PMID- 7996819 TI - [Fine structure of conjunctival lymphatic vessel valves]. AB - BACKGROUND: Lymphatic valves are due to ensure a zentripetal flow of lymph. The majority of the authors regard these valves as bicuspid structures with joint insertion points of the downstream localized free valvular edges. Because of that valvular structure a retrograde flow of lymph is impossible. Observations of our own however demonstrated retrograde flow of fluid under physiological conditions. In the following paper the structure of conjunctival lymphatic valves should be investigated or rather those structures, which were regarded as valves hitherto. Are there segmental connections, which allow retrograde flow of lymph? Is a regulation of lymph flow possible without self-acting valves? MATERIALS AND METHODS: In the conjunctiva of bovine post-mortem eyes (n = 100) segmental connections of lymphatic vessels with a diameter of less than 1 mm were opened specifically under control of slit lamp microscope after having undertaken an interstitial double contrast lymphography (solution of Berliner Blue/air). Some of these preparations (n = 20) could be investigated further on with the scanning electron microscope. That procedure allowed to make the patterns of flow and vessels structures in the beginnings of the lymphatic system observed with the slit lamp microscope congruent with those structures shown by the scanning electron microscope. RESULTS: The following segmental connections could be demonstrated: 1. Lymphatic vessels, which flow like a pipe into the wall of another segment. 2. Laterally arranged oval connections with valve resembling an aperture. 3. Segments of lymphatic vessels arranged in a line, which flow into one another between two hump-shaped protrusions with bicuspid valvular structures. Also the existence of different connecting structures ("valves") in one segment ("gear segment") were observed. In bulbus-like segmental connections arranged one behind the other with two valvular leaflets it could be demonstrated by scanning electron microscopy, that the two leaflets were attached apart at the vessel wall. That divergence to the previous models of lymphatic valves means, that these valvular leaflets cannot work as self-acting valves and prevent retrograde flow. CONCLUSIONS: However according to the valveless model of Libau a directed regulation of flow is possible. Perhaps the valvular structures described above play an important part by the interaction between the endothelium of lymphatic vessels and the substances transported in the lymph. The variety of segmental connections, the network of vessels with different diameters, which seem to be connected by feed-back, demand a new way of looking at the initial lymph flow. PMID- 7996820 TI - [Measles retinitis in an immunocompetent child]. AB - BACKGROUND: Measles retinitis is rare in immunocompetent patients and has recently been only sporadically described. This case report reveals the clinical picture, the course of the disease and the prognosis of this entity. HISTORY AND FINDINGS: One month after a diagnosed measles infection, a 12-year-old girl presented with a macular star and peripheral retinal oedema due to a diffuse vasculitis associated with visual impairment in both eyes. Perimetry, electroretinography, and fluorescein angiography revealed a necrotising process along the inflamed vessels. THERAPY AND COURSE: Without therapy vision improved and the macular changes decreased. Some of the paracentral scotomata and a discrete visual acuity defect could still be detected during the follow-up examinations after 2 1/2 and 7 months. CONCLUSIONS: The early diagnosis of measles retinitis by an ophthalmologist can be of great importance because an associated encephalitis could be treated medically if recognized early enough. PMID- 7996821 TI - [Corneal ulcer in chronic graft-versus-host disease: treatment with collagen shields]. AB - BACKGROUND: After bone marrow transplantation various ocular diseases have been described. Ocular involvement is very common in patients with chronic Graft versus-Host Disease (GvHD). These patients show clinical and histological evidence of a dry-eye condition in 60-100 per cent. A severe complication is the development of a corneal ulcer with possible corneal perforation. Two patients with a severe dry-eye condition and development of corneal stroma ulceration are described. The corneal ulcers healed after treatment with collagen-shield. HISTORY AND SIGNS: In a 13-year-old boy an allogeneic bone marrow transplantation was performed in April 1989 because of Fanconi's anemia. In November 1989 a severe dry-eye condition occurred due to GvHD with skin, liver, and gastrointestinal tract manifestation. In April 1991 he presented with corneal stroma ulceration of the right eye. In a 24-year-old patient an allogeneic bone marrow transplantation was performed because of chronic myeloid leukemia in August 1989. In December 1989 he developed dry-eye condition due to GvHD with skin, mucosa and liver involvement. In December 1991 a corneal ulcer of the left eye occurred. THERAPY AND OUTCOME: Repeated conjunctival and corneal smears were negative. Local antibiotic and antiviral treatment showed no effect. Corneal ulcers deteriorated progressively with corneal thinning. Both patients were therefore treated with daily collagen-shields and hourly polyvinyl-pyrrolidon eye drops resulting in healing of the corneal ulcer within 3 and 2 weeks respectively. CONCLUSION: Treatment of corneal stromal ulceration in dry eye condition caused by chronic GvHD is difficult. In noninfectious ulcers daily application of collagen-shields and hourly artificial tears may prevent severe ocular complications like corneal perforation. PMID- 7996822 TI - [Why is the gray cataract called "star"?]. AB - The adjective "starblind" has its origin in the 8th century. It describes the disease of eyes which are blind from cataract. This definition can be derived from the ancient Greek medicine and is the definition for a "starre" (which means inert) effusion behind the pupil. Martin Luther introduces the subject "Star" as a synonym for blindness. In the 18th century some linguists supposed this subject could be deducted from "starr blicken" (which means "to look motionless"). Even until today this misleading meaning is widespread although standard literature of linguistics as well as standard literature of the history of ophthalmology refer to the original meaning of this word. PMID- 7996823 TI - [Benign concentric annular macular dystrophy]. AB - In routine eye examination of a 32-year-old male patient an annular macular dystrophy was noted in absence of distinctive visual complaints. Visual acuity was 20/20, the photopic and scotopic electroretinograms were normal. The ring scotoma in perimetry and the macula finding in ophthalmoscopy corresponded to the fluorescein angiographic pattern. Color vision deficiency was only mild without any predominant axis of confusion. Benign concentric annular macular dystrophy is rarely described in literature. Differential diagnosis includes all 'bull's eye' conditions. PMID- 7996824 TI - [Co-thinkers]. PMID- 7996825 TI - [What is the function of cytokines?]. PMID- 7996826 TI - [Listening is most important. Detailed dialogue before surgery]. PMID- 7996827 TI - [Practical model for the introduction of standardized care in a surgical intensive care ward]. PMID- 7996828 TI - [Therapy of acute, non-complicated diarrhea in infants and children]. PMID- 7996829 TI - [What expressions may be used with pulmonary function tests?]. PMID- 7996830 TI - [Care of patients treated with artificial respiration 2]. PMID- 7996831 TI - [Happiness and the meaning of life]. PMID- 7996832 TI - Nutrition education needs and learning preferences of Michigan students in grades 5, 8, and 11. AB - An assessment of nutrition education needs and learning preferences of students in grades 5, 8, and 11 was conducted to target instruction toward areas of highest need and strongest interest of students using teaching methods they prefer. This research evaluated students' knowledge, attitudes, and practices related to the Dietary Guidelines for Americans, including knowledge of the new Food Guide Pyramid; attitudes about school lunches and learning about nutrition; nutrition topics of interest; and preferred methods for learning about nutrition. Although results varied across grade level, generally students need to learn about the Food Guide Pyramid; the relationship between dietary fat, weight status, and health; and food sources of fat, salt, and fiber. They want to learn about personal health--how to control weight, improve diet, and prevent disease- using instructional methods that actively involve them. Results provide information relative to students' interest, understanding, and application of the Dietary Guidelines. PMID- 7996833 TI - A nationwide survey of school health services delivery in urban schools. AB - To understand school health service delivery models, and to plan for reorganization of a local school health service, a telephone survey of school based health programs from around the country was conducted in 1992. Responses were elicited from 33 school departments in some of the largest American cities. Respondents described their current programs, obstacles they face, and approaches they have chosen to address the needs of urban schoolchildren. City size did affect amount of services provided overall, but a clear relationship existed between number of providers employed, and the number/amount of screening services available. Cities employed a range of strategies to enhance services, including collaboration with local health authorities, creation of school clinics, and billing for services. PMID- 7996834 TI - Early access to health care services through a rural school-based health center. AB - School-based health centers (SBHCs) and school-linked health centers (SLHCs) represent relatively new models for health care service delivery. This article examines the question: Are SBHCs accessible as defined by four criteria of accessibility: available, community-based, affordable, and culturally acceptable? A literature review and an examination of a rural SBHC providing care to young children are presented in this paper. Both support the hypothesis that SBHCs are accessible to children and families in the school community. In particular, this SBHC's enrollment rate of 98% and its usage rate of 99% provide strong evidence that SBHCs are culturally acceptable. Ten strategies for a successful SBHC are presented to assist in planning and implementation of other SBHCs. PMID- 7996835 TI - HIV education practices and training needs of middle school and high school teachers. AB - A statewide, cross-sectional survey was conducted among Texas secondary school teachers to determine the scope of HIV education provided and training needs. Among 269 participants, 199 (75%) taught HIV education. Investigator developed scales measured instructional emphasis, preparation adequacy, desire for future training, comfort, instructional effectiveness, social support, and instructional barriers. Alpha levels indicated high levels of internal consistency on all scales. Considerable variations were noted in instructional emphasis among 18 content areas related to HIV education. Lessons were predominantly self developed. Most teachers were self-taught with no formal training, relied primarily on traditional teacher-centered instructional methods, felt uncomfortable and ineffective using peer leaders and role plays, wanted additional training in all subject areas, and perceived others to be supportive. Comparisons between groups indicated middle school teachers spent less instructional time on HIV education, reported more instructional barriers, less support from district personnel, a poorer fit (coordination) of HIV education with other subjects, less adequate preparation, and less responsibility and effectiveness. High school teachers were more prone to want additional training. Differences in responses to individual scale items, major instructional barriers, and recommendations for teacher training are provided. PMID- 7996836 TI - Involving families in school health education: implications for professional preparation. PMID- 7996837 TI - The tobacco loop. PMID- 7996838 TI - A standard health form for all children. PMID- 7996839 TI - Time course of perfusion-induced myocardial edema resolution in rats. AB - Previous studies have demonstrated that crystalloid coronary perfusion can cause myocardial edema, but the time required for resolution of this edema has not been defined. Accordingly, studies were conducted in 30 rats. Myocardial edema was induced by coronary perfusion with 20 cc/kg of Plegisol (294 mOsm/liter) during aortic occlusion, which produced diastolic arrest. This was followed by whole blood reperfusion, which restored normal contractile function. Duration of reperfusion in minutes was zero (group 0, n = 6), one (group 1, n = 6), five (group 5, n = 6), or fifteen (group 15, n = 6). A control group (n = 6) was studied without edema or reperfusion. Data included heart weight and myocardial water content. Left ventricular pressure-volume curves were measured in groups 1, 5, and 15. Myocardial water content increased significantly from 75.7 +/- 0.5% (SD) in the control group to 79.7 +/- 1.1% (P < 0.05) in group 0 and then decreased significantly to 77.3 +/- 0.7, 75.2 +/- 1.4, and 75.3 +/- 1.6% in groups 1, 5, and 15, respectively. Water content in group 1 was also significantly greater than in groups 5 and 15. Heart weight changes were not statistically significant. Normalized pressure-volume relationships shifted rightward with increasing reperfusion time, but changes were not statistically significant. We conclude that edema induced by crystalloid coronary perfusion of the arrested heart resolves in the beating heart after less than 5 min of blood reperfusion. PMID- 7996841 TI - Endothelium-dependent microvascular responses to activated complement. AB - Infusion of Escherichia coli bacteria to cause high cardiac output bacteremia produces a differential microvascular response with constriction of large arterioles and dilation of small arterioles in skeletal muscle of rats. An important component to host-defense mechanisms during bacteremia is activation of the complement system. One part of this study explored the possibility that microvascular responses to bacteremia could be mediated by activation of the alternative complement cascade to alter skeletal muscle blood flow during sepsis. Complement activation by iv zymosan into unanesthetized (decerebrate) Sprague Dawley rats caused constriction of large arterioles and dilation of small arterioles in cremaster muscle, while cardiac output stayed normal or was elevated. These microvascular responses mimic those during bacteremia, suggesting that components of the complement system mediate skeletal muscle microcirculatory responses to live E. coli sepsis. The vasodilation response of small arterioles in skeletal muscle during bacteremia is endothelium-dependent and is mediated at least partially by endothelial-derived relaxing factor (EDRF). Complement activation gives products which interact with endothelial cells. Thus, a second part of this study explored the role of EDRF in the vasodilation of skeletal muscle small arterioles during activation of the alternate complement pathway. Blockade of EDRF action by hydroquinone totally abolished small arteriole dilation and large arteriole constriction responses to complement activation by zymosan infusion. PMID- 7996840 TI - Human endothelial cells are defective in diabetic vascular disease. AB - Diabetic vascular disease is characterized pathologically by endothelial cell (EC) hyperplasia and basement membrane (BM) thickening. One key question regarding the pathogenesis of diabetic vascular disease is whether the EC or BM or both are primarily defective and responsible for these pathological changes. Previous studies, which took the approach of creating artificial diabetic conditions, have been inconclusive. It is known, however, that the extracellular matrix may be altered by glycosylation as a result of hyperglycemia, thereby altering EC function. To begin to address this question and more closely mimic the situation in vivo, we characterized human diabetic EC harvested from insulin dependent diabetic mothers (IDDM) at the cellular and molecular levels. Human EC were isolated from both normal and IDDM umbilical cords and cellular functions evaluated using standard assays of attachment (% attached cells), proliferation (cpm/cell), resistance to detachment under shear stress (number of cells remaining attached), and glucose uptake (cpm/2 X 10(4) cells). Gene expression of major BM components (collagen type IV, laminin beta 1, and laminin beta 2) was quantified by Northern analysis. Diabetic EC demonstrated increased proliferation (two- to eightfold compared to normals), were 20-40% less resistant to shear stress and took up glucose 10-15% more slowly than normal EC. Furthermore, Northern analysis showed that the expression of major BM components was increased by an average of 10-18% in diabetic cells compared to normal cells. These results were consistent with in vivo observations and previously published data.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7996843 TI - Continuous microwave enhances the healing process of septic and aseptic wounds in rabbits. AB - Evidence indicates that local application of continuous microwave (CM) has positive effects, for instance, on skin grafts and white blood cells. To investigate the role of CM on local wound healing under different conditions (septic and aseptic), a study was performed in an animal model. Seventy-two rabbits were randomly assigned to four groups of 18 each: group 1 and group 2 consisted of animals with aseptic wounds, and group 3 and group 4 consisted of animals with infected wounds. In the medial third of the dorsolateral body of each animal a wound was prepared under local anesthesia. Animals of groups 1 and 3 received CM treatment, and those of groups 2 and 4 served as controls. The treatment consisted of an irradiation with CM (fixed frequency 37 GHz, power flow density 1 mW/cm2) for 30 min once per day for 5 (group 1) or 7 days (group 3). No other conservative or surgical methods were applied. Aseptic wounds were covered with a sterile dressing. Infected wounds of controls (group 4) were irrigated with 10% NaCl once a day. Measurements were visual analysis, planimetric, bacterial, and immunological tests. The wound surface of treated animals with aseptic wounds became dry and plicated faster, the daily decrease of the wound surface area being more than twice as large as that in the control group (group 2, P < 0.05). Complete epithelization and adhesion of wounds appeared around Day 19 (95% Cl, 18.3 to 20.1) in group 3 and around Day 31 (95% Cl, 29.5 to 32.7) in group 4.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7996842 TI - Transplantation of lac-Z-transduced microvascular endothelial cells into the skeletal muscle capillary bed of the rat hindlimb occurs independent of the duration of femoral artery occlusion after injection of cells. AB - The skeletal muscle capillary bed may be an ideal recipient site for transplantation of genetically modified autologous endothelial cells and thus provide a basis for a technique of somatic gene therapy that would be applicable to a variety of acquired and inherited human diseases. The purpose of this study was to test the hypothesis that adhesion of lac-Z-transduced microvascular endothelial cells (MVEC) in the skeletal muscle capillary bed in vivo is dependent on the duration of arterial occlusion after injection of the transduced MVEC. MVEC derived from the abdominal fat pad of syngeneic rats (Wistar F-455) were transfected with the BAG vector, a replication-incompetent retroviral vector containing the lac-Z gene for beta-galactosidase and the Tn5 gene for selection of the transduced cells by the neomycin analogue, G418. lac-Z-transduced MVEC were radiolabeled with 125I-PKH-95, and, after the femoral artery was occluded for 10 min, these cells (1 to 2 x 10(6)) were injected intraarterially into the rat hindlimb. In the experimental groups the femoral artery clamp was removed at 0, 60, or 120 min after injection. A control group without pre- or postinjection femoral arterial occlusion was also studied. Adhesion of MVEC in the skeletal muscle capillary bed (mean percentage of injected 125I activity) was determined in groups of 4 rats at 1 day, 1 week, and 1 month after injection. Adhesion of the transduced MVEC did not increase as the duration of femoral artery occlusion after injection was increased.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7996844 TI - Latency of skeletal muscle contraction after pulse train stimulation: an important factor in correct timing of skeletal muscle cardiac assist devices. AB - Various configurations of conditioned skeletal muscle are under investigation for cardiac assistance in patients with end-stage cardiac failure. Optimal timing of conditioned skeletal muscle contraction is essential for effective cardiac augmentation. However, unlike mechanical methods of assistance, skeletal muscle requires time to develop peak tension. We measured "time to 50% peak tension" and "time to 90% peak tension" using an electrical strain gauge in 12 canine latissimus dorsi muscles (6 untrained controls and 6 trained with 3 months of electrical stimulation at 25 Hz with a 15% duty cycle). The "time to 50% relaxation" and the "time to 90% relaxation" after discontinuation of the stimulus were also measured. Conditioned skeletal muscle required significantly more time to develop peak tension than unconditioned skeletal muscle. Relaxation was also significantly prolonged in conditioned muscle. Notably, conditioned lattisimus needed, on average, 0.35 sec to develop peak tension and 0.20 sec for 90% relaxation. Thus, 0.55 sec of each muscle contraction/relaxation cycle was devoted to development of peak tension and subsequent relaxation. At normal canine heart rates of approximately 120 beats per minute (0.50 sec per cardiac cycle), conditioned skeletal muscle may take up to 70% of each cardiac cycle (0.35 sec) to develop 90% of peak tension. The recognition of this phenomenon in conditioned skeletal muscle is important for effective contraction timing of both human and animal skeletal muscle assist devices. Development of proper conditioning regimens for such devices may benefit from identification of those training parameters which produce a minimal "time to peak tension." PMID- 7996845 TI - Effects of high-energy shockwaves on normal human fibroblasts in suspension. AB - To gain insight in the effects of shockwaves on human cells the relationship between the energy density and the number of shockwaves as well as their effect on suspensions of normal cells was studied. At energy densities of 0.37, 0.6, 0.78, and 1.20 mJ/mm2 fibroblasts were subjected to 50, 100, 250, 500, and 1,000 shockwaves. Each test was performed three times and one sample was used as control. A decrease in viability related to the logarithm of both the number (P = 0.0000) and the energy density (P = 0.001) of the shockwaves was statistically demonstrable 1 hr after the shockwave application. The energy density of the shockwaves has less influence on the viability than the number of applied shockwaves. Seeding of viable cells 1 hr after the shockwave application showed that the decrease in the 48-hr growth potential was statistically dependent of the number of applied shockwaves only (P = 0.0007). After 24 hr no difference in the 48-hr growth potential could be demonstrated between viable shockwave-treated cells and control cells. The literature as well as our own investigations in vitro and in vivo indicate that shockwaves have a logarithmic dose-dependent destructive effect on cells in suspension, but they also seem to have a dose dependent stimulating influence on the healing process in damaged tissues. Due to the logarithmic relationship between the viability and both the number and energy density of the applied shockwaves it might be expected that even excessive numbers of high-energy-density shockwaves don't soon lead to total destruction of all cells in the suspension.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7996846 TI - The role of the mucus gel layer in intestinal bacterial translocation. AB - The mucus gel layer is thought to be a vital component of the intestinal mucosal barrier. The purpose of this study is to determine if decreasing mucus production following ischemia and reoxygenation of the intestinal mucosa would alter bacterial translocation in an in vitro rat mucosal model. Clonidine was used to decrease mucus production associated with an ischemia/reoxygenation insult. Bacterial translocation was studied in a modified Ussing chamber using Escherichia coli K100. The quantity of mucus produced, as well as the incidence and quantity of bacteria translocating was measured. In the clonidine-treated animals, there was a significant decrease in the amount of mucus produced compared to the control animals. The clonidine animals also had a higher quantity of bacteria translocating during the reoxygenation period compared to the control animals. The mucus gel layer is protective against in vitro translocation of bacteria following an ischemia/reoxygenation insult. PMID- 7996847 TI - Increased safety by two-stage hepatectomy with preoperative portal vein embolization in rats. AB - We evaluated the usefulness of preoperative portal vein embolization (PVE) in rats for increasing the safety of liver resection. During PVE, portal vein branches that perfused the central and left lobes of the liver were embolized. Liver weight, the elimination of indocyanine green, and the number of Kupffer cells were examined 7 days after PVE and in intact rats. Then we examined rats that had undergone PVE (PVE group), rats in which the embolized part of the liver was resected 7 days after PVE (PVE-Hx group), rats without PVE in which the same lobes of the liver were resected (Hx group), and rats that had undergone a sham operation (sham-operation group) for liver weight, the mitotic index of the hepatocytes, serum alanine aminotransferase activity, total bilirubin, and antithrombin III activity. Some rats in the four groups received an intravenous injection of 0.5 or 2.5 mg/kg endotoxin 48 hr after the operation (the second operation, if done), and the 24-hr survival rate was calculated. Some rats given 0.5 mg/kg endotoxin were killed 6 hr after the injection, and the extent of liver injury was examined biochemically and histologically. Seven days after PVE, the nonembolized part of the liver was about twice the weight of the corresponding lobes in the intact rats, the density of Kupffer cells was doubled, and the hepatic function per unit weight was about the same as that in these controls. Hepatic dysfunction and the endotoxin-induced liver injury were significantly slighter in the PVE and PVE-Hx groups than in the Hx group. Preoperative PVE could make hepatectomy safer. PMID- 7996848 TI - Rapid superoxide production by endothelial cells and their injury upon reperfusion. AB - Cultured human umbilical vein endothelial cells (EC) were exposed to hypoxia for various time periods followed by reoxygenation, and production of both O2- and H2O2 by EC was measured using the cytochrome c and scopoletin methods, respectively. Production of significant amounts of O2- was observed as early as 1 min after reoxygenation, reached maximum at 3 min and seemed to decline thereafter. Production of H2O2 was observed slightly later than that of O2-. Endothelial cell injury during hypoxia/reoxygenation was determined by both the trypan blue dye exclusion and chromium release methods. Significant increase of EC injury was detected after reoxygenation by both methods. This injury was significantly inhibited by allopurinol but not by superoxide dismutase or catalase. These results indicate that the production of reactive oxygen metabolites by EC and EC injury occur very rapidly after reoxygenation, which has not been reported, and these should be taken in consideration for the understanding and treatment of the clinical reperfusion injury. PMID- 7996849 TI - The use of biodegradable amikacin microspheres to prevent vascular graft infection. AB - The following study was performed to determine if an antibiotic impregnated in a biodegradable polymer can prevent infection and eradicate inoculum bacteria from contaminated polytetrafluoroethylene vascular grafts. Poly(glycolide-co-dl lactide) amikacin microspheres (PAM) measuring 50-100 microns were designed to deliver 100 mg (PAM 100) or 300 mg (PAM 300) amikacin per unit dose. Twenty mongrel dogs had a short segment of infrarenal aorta replaced with a graft that had been bathed in a 2 cc solution of Escherichia coli and Staphylococcus aureus (3 x 10(8) CFU/ml). Dogs were divided into three groups: Controls had contaminated grafts placed and received no therapy; PAM 100 and PAM 300 were used, respectively, to cover the grafts in the other two groups. Animals were sacrificed 14 days postoperatively at which time grafts were examined and cultured. Among controls, 7/8 had clinical graft infections and all had positive cultures for S. aureus (8/8) or E. coli (5/8). None of the treated animals had clinical graft infections (P < 0.001). Positive cultures were obtained for S. aureus in 2/8 (P < or = 0.007) and E. coli in 0/8 (P < or = 0.03) PAM 100 dogs and for S. aureus in 0/8 (P < or = 0.0002) and E. coli in 0/8 (P < or = 0.03) PAM 300 dogs. Two PAM 100 and four PAM 300 dogs had rare growth of contaminant bacteria (NS). In conclusion, PAM can prevent clinical graft infection and completely eradicate a standardized bacterial inoculum. PMID- 7996850 TI - Vasopressin stimulates DNA synthesis in cultured rat hepatocytes. AB - Liver regeneration following partial hepatectomy is significantly impaired in rats with hereditary vasopressin (AVP) deficiency. This suggested that AVP might have a direct effect on cultured rat hepatocytes. Hepatocytes from male Sprague Dawley rats were isolated using a two-step collagenase perfusion technique and plated at a density of 10(5)/16-mm Primaria plate. After a suitable attachment period, hepatocytes were incubated with minimal essential media, AVP, AVP plus a specific AVP antagonist, or oxytocin. Hepatocyte proliferation was measured by [3H]thymidine incorporation ([3H]Thy) into hepatocyte DNA. AVP (10 nM) increased [3H]Thy significantly (and this effect was blocked by an AVP-specific antagonist (50 nM). Oxytocin had no effect on hepatocyte DNA synthesis. To further investigate the influence of AVP on hepatocyte proliferation, the effect of AVP on transforming growth factor-alpha (TGF-alpha)-stimulated hepatocyte proliferation was also studied. This combination was chosen based on the ability of AVP to inhibit the biologic effects of EGF (a TGF-alpha analog). There was significant attenuation of TGF-alpha (50 nM)-stimulated [3H]Thy in the presence of AVP (10 nM). In summary: (1) AVP stimulates proliferation of cultured rat hepatocytes. (2) The effect of AVP can be significantly abolished by a specific AVP antagonist. (3) The proliferative response of AVP is specific. (4) AVP significantly attenuates TGF-alpha-stimulated hepatocyte hepatic DNA synthesis. Further studies should elucidate the mechanisms for the effects of AVP on hepatic proliferation alone or in combination with other factors. PMID- 7996851 TI - The expression of regenerative growth factors in chronic liver injury and repair. AB - Acute hepatic injury initiates known cellular and molecular events for regeneration. In contrast, the molecular mechanisms of repair following chronic liver injuries have not been defined. Transforming growth factor alpha (TGF alpha) and hepatocyte growth factor (HGF) are hepatocyte mitogens whose in vivo expression in liver is central to the regulation of regeneration. To study the role of TGF alpha and HGF in liver injury and repair, we used a model of reversible biliary obstruction without a bilioenteric anastomosis. In rats, the common bile duct was obstructed either by a vessel loop suspended from the abdominal wall (LOOP) or by ligation and division (DLD). After 7 days of obstruction, animals were autopsied or were decompressed by subcutaneous release of the loop and then autopsied at 1, 2, 4, 7, or 10 days of postdecompression. Serum bilirubin (mg/dl) increased to 14.8 +/- 2.9 (DLD) and 10.3 +/- 3.0 (LOOP) (+/- SEM, NS, ANOVA) at 7 days of obstruction. Liver sections demonstrated equal ductal hyperplasia and collagen deposition after LOOP and DLD. Biliary decompression reversed bile duct proliferation and normalized bilirubin. Analysis of injured and repairing liver mRNA by ribonuclease protection assay showed that TGF alpha mRNA levels were not significantly altered by injury or during repair. HGF mRNA was elevated following obstruction and showed increased expression 1 day after decompression, peaking at 2 days of repair. This evidence of modulation of HGF during liver repair following chronic cholestatic injury suggests that HGF may have a role in cellular proliferation during repair or act as a compensatory growth factor during injury. PMID- 7996852 TI - Ribosomes as molecular energy machines. AB - The idea that ribosomes operate as biological molecular energy machines offers an alternative description to that based on the assumption that the functionally important motions in ribosomes are only coupled to thermal degrees of freedom. The alternative model assumes that the energy gained in GTP cleavage generates in the ribosomal complex a localized metastable region temporarily not interacting with thermal motions. The metastable region may move along a definite pathway and in distinct sites promote irreversible logical operations involved in polypeptide biosynthesis. The new alternative represents a more complex and advanced algorithm offering advantages in speed, accuracy, more sophisticated control, and better resistance to various kinds of noise. PMID- 7996853 TI - Interactions of mitochondrial ATP synthesis and the creatine kinase equilibrium in skeletal muscle. AB - In skeletal muscle, creatine kinase imposes constraints on the concentrations of phosphocreatine, creatine, ATP and ADP, which complicate our understanding of the regulation of mitochondrial ATP synthesis, because correlations between oxidation rate (Q) and metabolite concentrations cannot prove causal relations. Two kinds of theory of mitochondrial control in vivo have evolved, based on (i) the hyperbolic relationship between Q and cytosolic [ADP] and (ii) linear correlations between Q and, for example, free energy of ATP hydrolysis. This paper examines some relationships between these theories in order to show (i) to what extent they may be regarded as different expressions of the same metabolic mechanisms, (ii) how they can be understood in terms of general principles of feedback control, and (iii) how they explain relationships between mitochondrial function and resting metabolite concentrations. PMID- 7996854 TI - Colonization of the thymus by T cell progenitors: models for cell-cell interactions. AB - The early events of T-cell generation, i.e. seeding of bone marrow-derived progenitor cells onto the thymic stroma, involve a small fraction (up to 1%) of thymus cells and are not presently observable. However, these events are crucial in determining the outcome of thymic colonization. In previous studies we utilized an experimental in vitro model of thymic reconstitution by bone marrow cells to compare normal thymocyte development with the development in conditions of T-cell deficiency, and, in particular, in aging. These studies showed that progenitor cells from old donor bone marrow are deficient in their ability to colonize the thymus, in spite of their ability to divide earlier upon seeding. In this study we apply mathematical and computer modelling in order to analyse early T-cell development and the causes for the developmental disadvantage of old donor bone marrow cells. The results indicate that the competition for seeding niches in the thymic stroma determines the outcome of colonization. PMID- 7996855 TI - A method for filtering respiratory oscillations. AB - We present a method based on dynamical systems theory which can be used to filter time series in a way which is superior to classical Fourier decomposition. This method is applied to three data-sets, taken from respiratory measurements of two children in quiet and REM sleep. Our purpose is to filter the several different oscillatory mechanisms which operate, in order to provide clearer signals on which further analysis and diagnosis can be based. PMID- 7996856 TI - Quadriceps femoris activation changes in genu varum: a possible biomechanical factor in the pathogenesis of osteoarthrosis. AB - This study was designed to determine whether the presence of an alignment deformity of the lower leg, known as genu varum, causes abnormalities in individual- or group-activation of the surrounding knee extensors, a situation which might accelerate knee deterioration. Nine healthy women with normal tibial alignment were compared with nine age-matched healthy women with genu varum. The outcome measure of maximal quadriceps femoris activity was recorded during successive maximal concentric isometric and isokinetic contractions of the knee extensors performed on a dynamometer using surface electromyography. The results showed that, taken as a whole, the percentage utilization of quadriceps motor units was higher for those subjects with genu varum (p < 0.01). These findings demonstrate that the extensors surrounding a varus knee might function less efficiently than those surrounding a normally aligned knee. As such they suggest that pathological force generation across a varus knee might be caused, in part, by associated alterations in quadriceps tension generating capacity. PMID- 7996857 TI - DNA repair and the evolution of longevity: a critical analysis. AB - Comparative gerontologists argue that variation among species in DNA repair rates may explain differences in maximum lifespan, and support this claim with the observation that DNA repair rates and lifespan correlate positively among mammals. However, these findings may be confounded by both size and phylogeny. Repair rates and lifespan may be positively correlated because both are positively correlated with body size. In addition, previous comparative studies have not controlled for the potentially confounding effects of phylogeny. In this study, I elucidate why we might expect larger species to have higher DNA repair rates, independent of differences in lifespan, and use existing data to test whether the relationship between DNA repair rates and lifespan holds up after controlling for the potentially confounding effects of size and phylogeny. Reanalysis of the existing data suggests that there is little comparative evidence in favour of the hypothesis relating DNA repair rates and lifespan. PMID- 7996859 TI - Alphanumerical divisions of the universal genetic code: new divisions reveal new balances. PMID- 7996858 TI - Inheritance systems and the evolution of new levels of individuality. AB - Evolutionary transitions to new levels of individuality have usually been treated as a part of the "units of selection" problem. It has previously been assumed that the unit of transmission and heritable variation at each level is the same- that it is the DNA base sequence and its variations. It is suggested here that considering the nature and the role of hereditary variations produced by non-DNA inheritance systems is essential for understanding some evolutionary transitions. The argument is illustrated by considering the role of epigenetic inheritance systems (EISs), the systems responsible for cellular memory, in the transition from unicellularity to multicellularity. It is argued that EISs played a vital role in the transition to multicellularity and the evolution of complex ontogenies, as well as having an important effect on the evolution of developmental strategies which protect the multicellular individual from disintegrating into its component parts. An analogy between the transition to multicellularity and the transition to a cultural unit integrated by language is also suggested. PMID- 7996860 TI - Carcinogenesis, genetic instability and genomic entropy: insight derived from malignant brain tumor age specific mortality rate dynamics. AB - Aging-related carcinogenesis has been attributed to inherent genetic instability, which manifests in a multistep fashion by activation of oncogenes and inactivation of tumor suppressor genes. Malignant brain tumor cells display multiple-characteristic acquired genetic abnormalities in oncogenes and tumor suppressor genes. Age-specific malignant brain tumor mortality rates in the United States from 1962 to 1988 were interpreted by longitudinal Gompertzian analysis. Utilizing a thermodynamic perspective of the Strehler-Mildvan modification of the Gompertz relationship between mortality and aging, a measure of the rate of increase in informational entropy for those genetic factors involved in the carcinogenesis of malignant brain tumor was determined. Aging related carcinogenesis can be viewed as a natural consequence of increasing informational entropy of the genome. PMID- 7996861 TI - Clustering of low usage codons and ribosome movement. AB - A model is presented in which the distribution of low-usage codons in a message is a major factor in determining the impact that they will have on the translation rate and distribution of ribosomes on that message. This model is based on the assumption that low-usage codons are translated more slowly than normal codons, an assumption supported by various lines of published experimental evidence. Although the parameters used to develop this model are somewhat arbitrary, the main conclusions of this paper are consistent with a wide variation in the values of those parameters. In the model, low-usage codons arranged in clusters are much more effective in blocking ribosome movement on the message than ones that are dispersed. The effective size of the cluster is limited to the dimensions of the ribosome. It has been estimated that ribosomes on a message are spaced at least 27 nucleotides or nine codons apart. A ribosome translating a cluster of nine codons in which some or all of the codons are low usage will move more slowly than over a comparable stretch of message containing no low-usage codons. Owing to ribosome size, the ribosome immediately behind the stalled ribosome will move as slowly; it must wait for the stalled ribosome to move on before it can even begin to translate the difficult region containing the low-usage codons. When the low-usage codon cluster is at the 3' end, the message will eventually be occupied by a ribosome jam that will transmit back to the 5' end of the message. In the steady state, the slowing effect imposed by a cluster of nine low-usage codons at the 3' end of a message would be just as great as if the entire message was composed of them. If the cluster is situated in the middle of a message, the ribosomes will form a jam upstream of the cluster. The ribosome density downstream of the cluster will be considerably reduced from what it would be for the same message with no cluster. If the cluster is at the 5' end of the message, the density of ribosomes will be reduced over the entire length of the message but the overall translation rate per ribosome will be only slightly reduced. However, owing to the reduced number of ribosomes initiating, the efficiency of the message in protein synthesis will be considerably reduced.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 7996862 TI - The origin and evolution of the genetic code. AB - We argue that a primitive genetic code with only 20 separate words explains that there are 20 coded amino acids in modern life. The existence of 64 words on the modern genetic code requires modern life to read almost exclusively one strand of DNA in one direction. In our primitive code, both the original and the complementary sequence are read in either direction to give the same strings of amino acids. The algebra of complements forces synonymy of primitive codons so as to reduce the 64 independent codons of the modern code to exactly 20 independent separate words in the primitive condition. The synonymy in the modern code is the result of selection rather than algebraic forcing. The primitive code has almost no resilience to base mutations, unlike the third base redundancy of the modern code. Our primitive and the modern code are orthogonal. If palindromic proteins were coded by hairpin DNA or RNA, then (i) no punctuation would be needed; (ii) the reverse reading would give the same secondarily folded protein structure; and (iii) the sugar backbone would be read in the conventional 5' to 3' direction for the original arm and its complement. Modern copying of genetic material is almost always antiparallel. However, occasional parallel copying, as does occur in modern life, would give the complementary hairpin that would also read 5' to 3' along its entire length.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7996863 TI - Modeling HIV infection of CD4+ T-cell subpopulations. AB - We develop and analyze a set of models for the interaction of HIV with CD4+ T cells. We consider three major subpopulations of T cells: virgin, activated and memory. In our first model we assume that HIV can infect activated cells but not resting cells. We then generalize the model to take into account recent reports that HIV can enter resting cells but that such entry does not lead to the production of completely reverse transcribed copies of the viral genome or integration of the DNA copy into the host cell's genome unless cell activation occurs. Our models show that T-cell memory is greatly reduced by HIV infection and that T-cell depletion may be due to the direct killing of peripheral T cells and T-cell precursors in the thymus. PMID- 7996864 TI - Genetics of mutualism: the evolution of altruism between species. AB - Conditions are analyzed under which natural selection favors an individual to help another species at a cost to its own reproduction. Traditional models for the evolution of altruism between species focus on the genetic relatedness between the original donor and the recipients of return benefits from the mutualistic partner species. A more general model is analyzed here that focuses on the synergistic effects between partner species caused by genetic variability. The model shows that the spread of altruism is enhanced by spatial correlations between species in the genetic tendency to give aid to partners. These spatial correlations between species are similar to the kin selection coefficients of relatedness that determine the course of social evolution within species. The model also shows that natural selection and ecological dynamics can create genetic correlations between neighbors of different species, even when the initial spatial distributions of the species are uncorrelated. Genetic correlations between species may play an important role in the origin and maintenance of altruism between species. PMID- 7996865 TI - Development of an idiotypic network in shape space. AB - Based upon the shape-space formalism, a model of an idiotypic network including both bound and free immunoglobulins is simulated. Our point of interest is the network development in the context of self antigens. The investigations are organized around simulations initiated by various spatial configurations of antigens; the behavior of the system with respect to antigens is analyzed in terms of morphogenetic processes occurring in the shape space. For certain values of the parameters, the network expands by traveling waves. The resulting spatial pattern is a partition of the shape space into zones where introduction of an antigen entails an infinite growth of the clones binding to it, and into zones where, on the contrary, the anti-antigen idiotypes decrease. Among the parameter combinations tested, some produce a partition that remains static whereas others produce a partition that changes in time. For other values of the parameters, the patterns generated do not partition shape space into zones; in these cases, it is observed that the system systematically explodes when an antigen is present. PMID- 7996866 TI - Computer aided identification of a potential 5'-3' exonuclease gene encoded by Escherichia coli. AB - The predicted amino acid sequence of a previously overlooked open reading frame (ORF) from E. coli has been subjected to sequence analysis. The ORF, sequenced independently by two research groups, appears to encode a protein of 251 amino acids residues (25 kDa). The protein sequence shares a high degree of similarity with the amino acid termini of E. coli DNA polymerase I and other bacterial DNA polymerases (and phage-encoded enzymes) known to possess 5'-3' exonuclease activity. The newly identified E. coli gene, designated exo, is positioned downstream of signals characteristic of an efficient translation initiation sequence. Codon bias analysis indicates that the ORF has good protein coding potential. These observations indicate that the gene is likely to be expressed. The gene is 60% identical with the 5'-region of the E. coli DNA PolI gene (polA) over a 260 base-pair region. These two genes may have arisen by duplication of an ancestral gene or polA may have arisen by a recombination event involving exo. A comparison of the predicted secondary structures of 5'-3' exonucleases revealed the presence of several conserved regions of secondary structure, including a potential helix-turn-helix motif. PMID- 7996867 TI - Chronic myeloid leukemic granulocytes exhibit decreased adhesion to fibronectin. AB - Extracellular matrix components are known to regulate the process of egress of granulocytes from the bone marrow and their emigration to inflammatory sites. In this study we have compared the adhesion of normal and chronic myeloid leukemic granulocytes to fibronectin. Adhesion of granulocytes from leukemic patients to all the different concentrations of fibronectin assessed was significantly lower than that of normal individuals. This observation suggests that the decreased adhesion of leukemic cells to fibronectin may be responsible for their early egress from the bone marrow and their delayed emigration to the sites of inflammation. PMID- 7996868 TI - Immunophenotyping of childhood acute lymphoblastic leukemia in Saudi Arabia: second look. AB - Geographical variations in the incidence of disease are of considerable theoretical and practical importance. It has been claimed that the distribution of acute lymphoblastic leukemia (ALL) phenotypes in Saudi Arabia is different from that recorded in the Western literature. One hundred and twelve (112) patients under 15 years of age, diagnosed as ALL between January 1992 and May 1994 had immunophenotypes performed on their blast cells. Common ALL (cALL) together with pre-B-ALL, formed 86.5% of the total; B-cell 3%, T-cell 6% and null cell 4.5%. These figures are not significantly different from the Western literature. A previous claim from this institution in 1990, that both null and B cell ALL were significantly increased compared with elsewhere, is not supported by the present figures. Age and sex distribution, and FAB classification, L1 77%, L2 20% and L3 3%, were also of the same order as described elsewhere and, in particular, there was no increase in the frequency of L3 subtype. PMID- 7996869 TI - Inv(16) may be one of the only 'favorable' factors in acute myeloid leukemia: a report on 19 cases with prolonged follow-up. AB - We report our experience of treatment of acute myeloid leukemia (AML) with inv(16). Nineteen of 531 (3.6%) cases of newly diagnosed AML karyotyped over a 12 year period had inv(16)(p13q22) and none had t(16;16) or del 16q. Morphologically, all patients had M4eo. All patients were treated with conventional anthracycline-Ara-C chemotherapy, followed by moderate or more intensive consolidation chemotherapy. All patients received central nervous system (CNS) prophylaxis with intrathecal methotrexate and Ara-C, and cranial irradiation. Eighteen patients (95%) achieved complete remission (CR). Three had a bone marrow relapse, one had a CNS relapse and 14 patients remained in first CR, 11 of them with a follow-up greater than 44 months. Disease-free survival was 74% after 10 months, and actuarial survival 88% after 4 years, and 62% after 6 years. No other AML subgroup, in our experience, had a long-term survival approaching that of AML with inv(16) (although similar favorable outcome may be anticipated in acute promyelocytic leukemia treated by a combination of retinoic acid and chemotherapy). PMID- 7996870 TI - Karyotypically defined risk groups in acute myeloid leukaemia. PMID- 7996871 TI - Detection of t(8;21) by reverse transcriptase polymerase chain reaction in patients in remission of acute myeloid leukaemia type M2 after chemotherapy or bone marrow transplantation. AB - Seven patients with acute myeloid leukaemia (AML) type M2 and t(8;21), treated with intensive chemotherapy followed in two cases by allogeneic or autologous bone marrow transplant (BMT), were tested for the presence of transcripts of the characteristic chimaeric gene AML1/ETO by reverse transcriptase polymerase chain reaction (RT-PCR) at serial intervals during remission. Six patients, including both BMT patients, demonstrated persistence of t(8;21), one being consistently negative in peripheral blood but bone marrow positive. Bone marrow may, therefore, be more reliable than peripheral blood for detecting residual t(8;21) cells. Our results show persistence of t(8;21) cells in AML-M2 patients following chemotherapy or BMT, some of whom were in long-term remission. PMID- 7996872 TI - Selection and characterization of an erythroeosinophilic subclone (LAMA-87) and an eosinophilic subclone (LAMA-88) from the multipotential cell line LAMA-84. AB - The human leukemic cell line LAMA-84 was established and characterized as an erythromegakaryocytic cell line. In the present study we show that these cells can differentiate in estrone-treated athymic mice and give rise to an erythroeosinophilic cell line (LAMA-87). This new cell line expressed glycoporin A, alpha beta and gamma globin chain mRNA but also eosinophilic peroxidase. Hemin slightly increased the total hemoglobin production of the cells and phorbol diester (TPA), dimethyl sulfoxide (DMSO) and sodium butyrate (SB) increased the expression of megakaryocytic markers (gpIIb/IIIa complex). When inoculated into non-treated athymic mice, LAMA-87 cells can differentiate to give rise to eosinomonocytic cells (LAMA-88). This new cell line expresses eosinophilic peroxidase, Luxol fast blue stain and synthesizes lysozyme. Depending on the inducer used, LAMA-88 can differentiate along a monocytic lineage (TPA, DMSO, SB and vitamin D3). These three LAMA cell lines should be useful in further studies of the molecular regulation of the pluripotent cell commitment and may provide a model for the understanding of human hematopoiesis. PMID- 7996873 TI - Leukemia cell lines: in vitro models for the study of chronic myeloid leukemia. AB - The clinical importance of CML lies in its poor responsiveness to chemotherapy which has proved highly effective in treating ALL. The scientific importance of CML resides in its role as a cancer prototype, permitting the identification of genes centrally involved in both neoplastic change and normal cellular differentiation. One of these genes, the fusion gene BCR/ABL resulting from the balanced translocation (9;22) has received wide attention owing to its intimate involvement in CML. Although a tremendous amount of data have been recently discovered about BCR/ABL, its exact role in leukemogenesis and normal hematopoiesis remains obscure. The study of CML cell lines has already been of considerable help in understanding the molecular events associated with the Ph chromosome [4]. Further advances are likely to be forthcoming, particularly at the molecular genetic, but also at the protein level. CML cell lines may offer an excellent means of addressing many issues as continuous cell lines represent an inexhaustible source of identical cell material that, in addition, can be made available to other researchers around the world. This overview on the thus far reported CML-derived cell lines supports the hypothesis that in some specimens of CML the target cells in which Ph translocation arises are not necessarily lineage restricted committed progenitor cells, but are in fact in some (or all?) cases precommitted bipotential or multipotential progenitor or stem cells retaining the potential for differentiation in diverse hematopoietic directions [26]. In conclusion, established tumor cell lines with their unique phenotypic and karyotypic features have been extremely useful models for investigation of the molecular and biological characteristics of CML. Considerable progress in understanding the molecular and cell biology of CML has been achieved. Further advances in the knowledge of CML are expected to accrue with the productive use of these powerful research tools for many important unresolved issues. By so doing, these discoveries might open new avenues that promise to move clinicians closer to the goal of the prevention or cure of CML in all patients. PMID- 7996874 TI - Expression of 1D8--a novel non-sialylated B-cell-associated carbohydrate epitope in lymphoproliferative disorders. AB - The expression of a novel B-cell-associated carbohydrate epitope (1D8) was studied by means of flow cytometry in 153 well defined cases of leukemias and lymphomas and 19 cases of lymphadenopathy used as controls. The 1D8 epitope was detected preferentially in proliferations of mature B-lymphocytes (11/15 CD20+ acute lymphoblastic leukemia (ALL), 14/16 chronic lymphocytic leukemia (CLL), 4/7 mantle cell non-Hodgkins lymphoma (NHL), 3/8 follicle cell NHL. However its expression did not appear lineage- or differentiation stage-restricted. Intensive expression on in vivo and in vitro-activated lymphocytes as well as in some high grade malignancies indicated a relationship to the functional state of cells. Bearing in mind the enhanced detection of 1D8 upon desialylation, the epitope might be involved in the regulation of adhesion/migration potential of normal leukocytes and their malignant counterparts. PMID- 7996875 TI - Influence of idarubicinol on the antileukemic effect of idarubicin. AB - We investigated the antileukemic potency of idarubicinol (IDAol), a 13-dihydro (13-OH) metabolite of idarubicin (IDA), on the HL60 line of human leukemia cells. In contrast to daunorubicinol (DNRol) and to doxorubicinol (DOXol), IDAol showed an extensive accumulation in HL60 cells. The high affinity for DNA and the strong DNA cleavage activity of IDAol were comparable to values for IDA; consequently, IDAol was strongly cytotoxic against HL60 cells. IDAol may play an important role in the clinical efficacy of IDA in patients with acute leukemia, particularly since it persists in the blood for prolonged periods after the administration of IDA. PMID- 7996876 TI - [The initial symptom attributable to cancer in digestive tube tumors. A study of agreement between the patient and the physician]. AB - BACKGROUND: Clinical practice shows that certain patients may underestimate and others overestimate some initial symptoms of their disease. In studies on the interval between first symptoms and treatment onset, estimating the date in which symptoms first appeared is crucial. The study analyzed patient-physician agreement in assessing first symptom attributable to cancer. METHODS: During two years, two physicians personally interviewed, through a structured questionnaire, all symptomatic patients with a neoplasm of the digestive tract admitted to Hospital del Mar (Barcelona, Spain). Patients had a mid-low sociocultural profile and most had been admitted through the Emergency Department. RESULTS: Absolute agreement (symptom and date) occurred in 85% of the 183 subjects. In most discordant cases, patients had overlooked some component of the "toxic syndrome", and the date of symptom onset was, based on physician's assessment, chronologically prior to the date elicited from the patient. Disagreement was directly related to the patient's health status (p < 0.05) and to the number of reported symptoms until hospital admittance (p = 0.002), but not to tumour stage. Agreement increased with the importance attributed by the patient to the first symptom (p < 0.05). CONCLUSIONS: In spite of difficulties inherent to measuring symptomatic onset of diseases, structured patient interviews appear to be a reasonably valid method and deserve further development in this and other areas of research. PMID- 7996877 TI - [Study of the influence of labor and sociodemographic factors on the development of professional burnout syndrome in the area of specialized medicine of INSALUD in Avila]. AB - BACKGROUND: The burnout syndrome is characterized by emotional exhaustion (basis of the decrease of self-esteem), depersonalization and decrease of the feeling of personal accomplishment, above all, in the field of professional achievements. It appears to be frequent in the helping professions and the human services workers, and in its origin labour factors seem to intervene. The authors intend to determine the degree of burnout among physicians and to assess the influence of labour and sociodemographic factors on the emotional state of physicians. METHODS: One hundred fifty-six physicians of the Avila Health Service Area participated. A general questionnaire and the Spanish version of the Maslach Burnout Inventory were used. The statistical analysis includes the analysis of variance, the Pearson's correlation coefficient and the Student's t test. RESULTS: The profile of the studies professional is a 37 year old male, married, who has been working for 13 years in his profession and who has had his current job for eight with a professional category of consultant. In general, they are not satisfied with their work, they do not value highly the personal policy of their managers and they hardly identify themselves with the enterprise, if at all. These negative labour aspects were correlated with the burnout syndrome, whose values indicated high levels of professional exhaustion. CONCLUSIONS: Improvements in the work conditions are suggested and in its organization such as the physicians' participations in management, definition of positions and assessment of individual situations. PMID- 7996878 TI - [What does the average stay say about the diagnosis-related groups?]. AB - BACKGROUND: The systems for classifying patients into homogeneous groups of resource consumption such as diagnosis related groups (DRG) use mean stay (MS) as the principal predictive variable of this consumer entity. The standard of MS for each DRG is usually defined as the MS of this DRG in one group of hospitals. This method omits the existence of unnecessary days of hospitalization which are added to the standard and may be identified by review of hospitalary use. METHODS: A retrospective review of the clinical need for 933 days of hospitalization (190 days of admission plus 743 successive stays for the same) in 190 cases of 167 DRG (appendicectomy without complications or comorbidity in those under the age of 70 years) in 8 public hospitals in Valencia (Spain) was performed by the Appropriateness Use Evaluation Protocol. RESULTS: Four days of admission (2.1%) and 284 successive stays (38.2%) were considered unnecessary from a clinical point of view. Necessary MS was estimated as 3.4 days for GRD vs the 5.1 days of MS observed. CONCLUSIONS: The common construction of standards of mean stay per disease demonstrates an important proportion of unnecessary use of hospitalization, the correction of which would allow a reduction in the mean costs of the process without a reduction in the quality of care. PMID- 7996879 TI - [The symptom above all]. PMID- 7996880 TI - [Self esteem among physicians and health care reform]. PMID- 7996881 TI - ["Dynamic" factors in Brown-Sequard syndrome, their implications from a "functional" perspective of the central nervous system and its pathology]. PMID- 7996882 TI - [Recommendations on immunization strategies for the prevention of hepatitis B. Scientific Societies (Spanish Association for the Study of the liver, Spanish Society for Infectious Diseases and Clinical Microbiology, Spanish Society of Hospital Hygiene and Preventive Medicine, Spanish Society of Family and Community Medicine, and Spanish Society of Pediatrics [Neonatology section])]. PMID- 7996883 TI - [Philosophy for physicians]. PMID- 7996884 TI - [Hafnia alvei isolated in acute gastroenteritis]. PMID- 7996885 TI - [Late medical care for HIV-infected patients]. PMID- 7996886 TI - [Response to cutaneous ulcers and ischemic pain to pulsed therapy with cyclophosphamide in antiphospholipid antibody syndrome]. PMID- 7996887 TI - [Colchicine poisoning and multiple organ failure]. PMID- 7996888 TI - [Pustular dermatitis in Salmonella enteritidis infection]. PMID- 7996889 TI - [Urinothorax: an infrequent cause of pleural effusion]. PMID- 7996890 TI - [Emergency hospital admission in medical services: causes, justification, social factors, and their differences in function of age]. AB - BACKGROUND: Increasing attention has been given to the care to elderly patients in emergency departments (ED). Moreover, few data are available about final phase of the process, that is hospital admission from ED. This study was conducted to establish appropriateness, reasons and social factors related to hospital admission in medical services from ED and their age-related differences. METHODS: The Appropriateness Evaluation Protocol scale (AEP) was applied prospectively to 515 patients 15 years and older admitted to medical services through an ED. Patients who did not meet any AEP criteria were evaluated for other medical or social factors as conditions for their admission. RESULTS: The sample was composed by 303 elders (65 years and older, mean age = 77 +/- 6 years) and 212 adults (15-64 years old, mean age = 45 +/- 14). 271 elderly patients (89.4%) and 173 adults (81.6%) meet AEP criteria (p = 0.01). Hospitalary admission for diagnostic procedures is more frequent in younger than in older group (14.2% versus 6.9%, p = 0.01). No differences are detected in hospital admissions based upon strictly social factors: 7 (2.3%) in elderly group and 7 (3.3%) in younger one (p = 0.05). CONCLUSIONS: Urgent hospital admissions in medical services are justified more frequently in elderly patients. These patients are admitted for diagnostic procedures less frequently than younger group. No age-dependent difference in strictly social admissions is detected. PMID- 7996891 TI - [Seroepidemiologic survey of hepatitis A antibodies in the young adult Spanish population. Spanish Study Group on hepatitis A (1)]. AB - BACKGROUND: The aim of the present was to study the rate of exposure to the hepatitis A virus (HAV) in the young adult Spanish population. METHODS: A transversal observational study was performed to evaluate the prevalence of anti HAV antibodies (IgG) in a representative sample of the Spanish population between the ages of 20-40 years. Information on demographic variables (age, place of residence, education, number of children and number of brothers or sisters) and history of hepatitis was collected. A blood sample was also obtained from the umbilical cord or heel of newborns. The level of total anti-HAV antibodies was measured by the ELISA method. RESULTS: A total of 1,204 pregnant women the ages of 20-40 years with deliveries in 71 hospitals in 14 autonomic regions were included in the study. A total of 606 positive anti-HAV were reported representing a prevalence of 50.4% (CI 95% = 48-52%). The prevalence was seen to significantly increase in relation to age, from 39% (group from 20-25 years) up to 60% (groups from 31-35 and 36-40 years of age). The factors of "education" and "number of children" were not associated to greater risk of previous contact with HAV. A non significant increase in prevalence was observed in relation with "number of brothers or sisters of the parturient". 86.3% (CI 95% = 83-93) of the positive anti-HAV subjects reported not having had clinical history of hepatitis. CONCLUSIONS: Half of the young Spanish adult population does not show antibodies against the hepatitis A virus, with an increase in morbidity by clinical hepatitis A being foreseen in this age group. PMID- 7996892 TI - [Percutaneous endoscopic gastrostomy: study on 35 patients]. AB - BACKGROUND: A review of the technique, indications, complications and follow up of percutaneous endoscopic gastrostomy (PEG) was performed. METHODS: Thirty-five patients in whom a PEG had been placed according to the Ponsky technique from 1991 to 1993 were analyzed 27 of whom had neurologic disease, 6 tumoral diseases and 2 other causes. RESULTS: PEG was carried out in 33 patients with no incidences while the technique could not be performed in 2 since the point could not be identified by transillumination in the gastric wall. No immediate complications were observed. Seven minor early complications were presented as wound infection with the cannula being withdrawn in only one case due to persistence of the infection. Five late complications were reported: 1 severe (gastrocholic fistula) and 4 minor (2 cannula obstructions, 1 displacement and 1 infection). Evolution was followed in 31 patients with the cannula being withdrawn in 4 (2 because of complications and in the other 2 on initiation of oral diet). The cannula was substituted at 120 and 360 days in 2 patients. Sixteen patients died, 5 during the first 30 days due to the primary disease, with only one case (aspirative pneumonia) being related to the PEG. The PEG continues functioning in 11 patients. CONCLUSIONS: Percutaneous endoscopic gastrostomy for feeding is a simple technique which may be carried out in most patients with scarce severe complications, allowing a good nutritional state and improving the quality of life of patients requiring prolonged enteral feeding. PMID- 7996893 TI - [Why do patients use hospital emergency services?]. PMID- 7996894 TI - [From HIV infection to AIDS: immunobiologic mechanisms]. PMID- 7996896 TI - [Use and abuse of the passive voice in the medical written language]. PMID- 7996895 TI - [Acute myopathy related to the administration of glucocorticoids and neuromuscular blockers]. AB - Two cases of acute myopathy following the administration of high doses of glucocorticoids in patients requiring mechanical ventilation and who were also administered neuromuscular blockers are presented. The patients were two women of 57 and 73 years of age. The doses of methylprednisolone administered were of 810 and 1,180 mg during the first 7 and 17 days, respectively. With regard to the total doses of neuromuscular blockers the first patient received 76 mg of pancuronium over 4 days while the second received 1,180 mg of atracurium over 17 days. This myopathy is characterized by a clinical and histological picture which differs from that associated to the chronic use of glucocorticoids being attributed to a toxic action of these drugs somewhat favored by immobilization due to the use of neuromuscular blockers. Given the lack of references in the literature on this entity in Spain a review was undertaken with the need for correct early diagnosis allowing differentiation from other causes of weakness such as ischemia of the cerebral trunk, polyradiculoneuritis and polyneuritis of critical patients being of note. Muscular biopsy is therefore very useful since very suggestive signs of this myopathy may be found. The disease is reversible with no effective treatment. An early rehabilitation program is the only method of shortening the convalescence period. PMID- 7996897 TI - [Assessment of the contribution from scholarship holders to the scientific production at the Hospital Clinic i Provincial de Barcelona (1980-1990). Research Committee of the Hospital Clinic i Provincial de Barcelona]. PMID- 7996898 TI - [Protocols for the prevention and treatment of thromboembolic disease (V). Thrombolytic therapy in peripheral arterial disease. The Editorial Committee on Protocols]. PMID- 7996899 TI - [Current alternatives in the treatment of Pneumocystis carinii pneumonia in patients with AIDS]. PMID- 7996900 TI - [Oral leishmaniasis in a patient with the human immunodeficiency virus]. PMID- 7996901 TI - [The use of lovastatin in patients with hyperlipemia following heart transplantation treated with cyclosporine]. PMID- 7996902 TI - [Recurrent Mycobacterium tuberculosis bacteremia in AIDS: subtherapeutic concentrations of antitubercular agents?]. PMID- 7996903 TI - [Usefulness of 99mTc-sestamibi gammagraphy in the localization of ectopic parathyroid glands]. PMID- 7996904 TI - [Prevalence of respiratory diseases in a rural population in the north of Catalonia: La Cerdanya]. AB - BACKGROUND: There are few epidemiological studies on health respiration in the population of Catalonia (Spain). This is a cross-sectional study of prevalence about respiratory diseases in a rural population in La Cerdanya (Catalonia). METHODS: The sample was obtained by a simple random method among the Cerdanya population older than 6 years. The questionnaire used was from the American Thoracic Society for the Division of Lung Disease with an annex attached for extrinsec allergic alveolitis which was worked out. RESULTS: The smoking prevalence was 24.2%, among the farmers (17.1%) was lower than the general population, and it was higher in the men (36.0%). The bronchitis chronic symptoms prevalence was 9.2%, higher in the men (11.3%). The bronchial asthma symptoms prevalence was 4.8% and the farmer's lung symptoms was 0.2% in the general population and 1.0% among the farmers. CONCLUSIONS: The smoking frequency La Cerdanya is lower than in the rest of Catalonia, probably because the farmers have a lower prevalence of smoking. The smoking habit and chronic bronchitis is higher in males. The chronic bronchitis prevalence in farmers with moderated or severe contact with organic dust is higher than in the farmers with lighter contact. PMID- 7996905 TI - [Enterococcus sp. resistance, a growing problem. Epidemiologic study (1987 1993)]. AB - BACKGROUND: Infectious processes caused by Enterococcus species currently constitute a growing problem due to the rapid appearance of resistances and the scarce existing therapeutic alternatives. The patterns of in vitro resistance to ampicillin, vancomycin and gentamycin were therefore studied in addition to their evolution over time of the isolates of Enterococcus sp. identified in the Salamanca University Hospital from 1987-1993. METHODS: Data were obtained from a computerized system of epidemiologic surveillance of infection in in-patients on the basis of microbiologic information. Sensitivity tests were performed by the disc-plate diffusion method of the National Clinical Committee for Laboratory Standards. RESULTS: Global resistance was 2.1% to vancomycin versus 8.3% to ampicillin with most of the isolates being resistant to gentamycin. The frequency of appearance of resistance increased over time with 19.6% of the strains found to be resistant to ampicillin (p < 0.05; CI 95%, 1987-1988: 12.2-24.3%) in 1993 and from 1991-1992 2.7% were found to be resistant to vancomycin. The strains from patients from the medical area were more resistant to ampicillin (p < 0.05; CI 95%, 0.8-7.4%) and vancomycin (p < 0.05; CI 95%, 0.2-3.9%) than those corresponding to patients from the surgical area. Greater resistance was identified to ampicillin and vancomycin in the isolates from urine and wound exudates. Patients under the age of 1 year were significantly less resistant to ampicillin (p < 0.05; CI 95%, with respect to the group from 21 to 40 years: 1.6 13.9%) and vancomycin with the greatest resistance being found from 41 to 60 years of age. E. faecalis (2.9% resistance) was more resistant to vancomycin and E. faecium was more resistant to ampicillin (27.8% resistant strains) (p < 0.05: CI 95%, 3.2-33.6%). CONCLUSIONS: Over time there has been a rapid increase in the number of enterococci resistant to ampicillin while, to date, vancomycin shows good activity against these bacteria. PMID- 7996906 TI - [How many cases of tuberculosis are not reported?]. AB - BACKGROUND: The aim of this study was to evaluate the degree of registry of tuberculosis and the factors associated to the same. METHODS: A retrospective study of the cases of respiratory tuberculosis diagnosed in the hospital A. Marcide-Novoa Santos (El Ferrol. La Coruna. Spain) from 1990 to 1992 was carried out. Identification was obtained from the registries of microbiology and pathology and the clinical history files. Registered cases were obtained from the nominal notifications to the Epidemiology Department of the local health service department. Sex, age, place of residence, previous history of tuberculosis, HIV, diagnostic method, localization of the tuberculosis, registration and reporting physician were evaluated for each patient. RESULTS: Three hundred ninety-three cases were identified of which 78 (19.8%) had been registered. Age and pulmonary localization were the variable influencing the degree of registration. Reporting was greater in the age group from 0 to 10 years (p < 0.05). Pulmonary tuberculosis was the most reported type although only 22.4% of the cases were declared. Bacilloscopy was positive in sputum in 190 patients and declared in 46 (24.2%). The degree of registration increased significantly over three years (p < 0.000001). Sex, previous history of tuberculosis, infection by the HIV and diagnostic method did not influence the degree of registration. CONCLUSIONS: Seventy-five percent of the cases with positive bacilloscopy in sputum were not declared. The degree of declaration has improved over time, however, remains deficient being 2.7 fold lower than the total number of cases diagnosed in 1992. PMID- 7996907 TI - [The air in La Cerdanya]. PMID- 7996908 TI - [Sick building syndrome (diseases related with buildings]. PMID- 7996909 TI - [Candida vulvovaginitis]. PMID- 7996910 TI - [A 43-year-old woman, treated with mitral commissurotomy, with pulmonary nodules and polyarthritis]. PMID- 7996911 TI - [The diagnosis of primary pulmonary hypertension]. PMID- 7996912 TI - [Prevalence of elderly population requiring chronic home care]. PMID- 7996913 TI - [Pneumococcal vaccine in patients over 65 years of age: recommendations and role of primary care]. PMID- 7996914 TI - [Bone metastasis in bones with Paget's disease]. PMID- 7996915 TI - [Post-transfusion hepatitis in Navarra. Evidence of acute hepatitis C virus infection without elevation of aminotransferases]. AB - BACKGROUND: To determine the incidence of postransfusion hepatitis (PTH) and hepatitis C virus (HCV) infection in blood recipients in Navarra and to evaluate the impact of excluding anti-HCV positive donors on the incidence of posttransfusion HCV infection. METHODS: 248 transfusion recipients were included, 150 in a first period before anti-HCV(+) donors exclusion, and 98 in a second period after their exclusion. A serum sample from each patient was collected, bimonthly during the first month and monthly for six months, and another serum sample, twelve months after transfusion. ALT and anti-HCV were tested in each sample with ELISA and RIBA 2nd generation. HCV-RNA was determined with a nested polymerase chain reaction assay. RESULTS: PTH incidence in 1989 was of 2.9%. This incidence decreased to 1.1% after anti-HCV ELISA 1st generation positive donors exclusion. At present, this incidence, with anti-HCV ELISA 2nd generation positive donors exclusion, is 0.8%. 80% of PTH were caused by HCV. 50% of HCV acute infection, confirmed by positive PCR, had normal ALT. CONCLUSIONS: In Navarra, HPT incidence is below 1% after anti-HCV(+) donors exclusion. There are subclinics forms of HCV acute postransfusional infection with normal ALT. PMID- 7996916 TI - [The prevalence of anti-HCV positivity among blood donors in Asturias. A clinical epidemiologic study]. AB - BACKGROUND: The aim of this study was to know the prevalence, epidemiology, clinical manifestations and analytical changes present in anti-HCV positive blood donors detected in Asturias. METHODS: A prospective analysis of the incidence and prevalence of anti-HCV positivity in the blood donations carried out in Asturias from October 1989 to October 1991 was performed, as was a clinical and analytical study of the anti-HCV positive cases who attended a clinic specifically created for the same. RESULTS: The prevalence of the anti-HCV was 0.87% of the donors (372/42,789) and 0.50% of the donations (372/73,831) being higher among new donors (1.77%, 165/9,322). Of the 288 cases studied (77.4%), only 51 (17.7%) had been transfused and 105 (36.5%) lacked the previous parenteral risk factor. Only 31 (10.8%) presented symptoms or signs of liver disease and the positivity of the anti-HBc was not associated to any relevant analytical change. The existence of previous major surgery or transfusion was variable with the independent predictive value versus a negative anti-HCV control group. The mean follow up was 12.4 +/- 7.3 months (6-30 months) with an increase in aminotransferases (ALT) being detected in 108 cases (52.7%). A good correlation was found between this data, an ELISA-2 score greater than 5 and RIBA-2 positivity: of the 177 cases in whom RIBA-2 was determined this was found to be positive in 109 (61.6%); 84 cases (77.1%) had an increase in ALT and 100 (91.8%) an ELISA-2 score greater than 5. CONCLUSIONS: In Asturias the prevalence of anti-HCV positivity among blood donors is almost 1% and is greater if new donors are considered, being confirmed by RIBA 2 in 61% of the cases. The subjects are usually asymptomatic and up to one third of the same lack any known risk factor, while almost half have hypertransaminasemia during follow up. PMID- 7996917 TI - [Clinico-epidemiologic study of bacterial meningitis in Aragon]. AB - BACKGROUND: The aim of the present study was to know the incidence, etiology, prognostic factors and rate of mortality of bacterial meningitis in Aragon (Spain). METHODS: The clinical records of all the patients with bacterial meningitis seen in the hospitals in Aragon (Spain), from 1985 to 1988 inclusive were reviewed. RESULTS: The mean of the annual rates of incidence for Aragon (Spain) was 7.52/100,000 inhabitants. In patients under the age of 15 years the most frequent etiologies were Neisseria meningitidis (59.0%), Haemophilus influenzae (13.7%) and Streptococcus pneumoniae (9.4%); the global rate of mortality was 3.5% similar to that of sequelae. In those over the age of 14 years, the most frequent etiologies were N. meningitidis (33%), S. pneumoniae (18.4%) and Staphylococcus spp. (13.6%); the rate of global mortality was 19.5% and that of sequelae 10.8% with resistance of S. pneumoniae to penicillin and/or ampicillin in 45.5% of the cases in children and in 26.3% in adults. No significant evolutive differences related with the existence of resistances or the administration of antibiotics prior to lumbar punction were observed in any of the age groups. CONCLUSIONS: N. meningitidis is the main etiologic agent in Aragon in both children and adults. The greatest rates of mortality and sequelae were observed in the youngest and oldest age groups with a similar relation being seen in infection by gramnegative bacilli and S. pneumoniae, thus making these patients to be considered as being at high risk. PMID- 7996918 TI - [Hepatitis C, another plague]. PMID- 7996919 TI - [Significance and clinical application of new laboratory techniques for the study of infection by the human immunodeficiency virus]. PMID- 7996920 TI - [Castleman's disease: description and comments on 3 cases]. AB - Three representative cases of the clinical heterogeneity of Castleman's disease are presented: one localized form with hialine vascular histology (HV) and 2 multicentric forms corresponding to the plasmocellular variety (PC). The asymptomatic patient with HV was treated with surgical resection of one tumor. The 2 patients with the symptomatic PC variant were characterized by the different clinical presentation receiving polychemotherapy and steroids, respectively with good response. The literature is reviewed and the pathogenetic, clinical and therapeutic aspects of the disease, which remains difficult to define as a sole entity, are discussed. PMID- 7996921 TI - [Hereditary breast cancer: genetic bases and clinical features]. PMID- 7996922 TI - [Severe acute liver insufficiency in a 72 year old male with idiopathic myelofibrosis]. PMID- 7996923 TI - [The prevalence of obesity in Orihuela, Alicante, Spain. A comparison with the data from the National Health Care Survey in Spain]. PMID- 7996924 TI - [The requisites of uniformity and the attribution of authorship]. PMID- 7996925 TI - [Dilated myocardiopathy]. PMID- 7996926 TI - [The submandibular fold]. PMID- 7996927 TI - [Adenocarcinoma of the colon: presentation as fever of unknown origin]. PMID- 7996928 TI - [Progressive resistance to fluconazole in a patient with HIV infection and recurrent oropharyngeal candidiasis]. PMID- 7996929 TI - [Evaluation of different methods for detecting resistance of staphylococcus aureus strains to methicillin]. AB - Resistance to methicillin of 70 Staphylococcus aureus isolates from infection and 6 standard strains was evaluated by screening and disc diffusion techniques. Amongst wild S. aureus isolates 28 were identified as methicillin-susceptible (MSSA), 18 as heterogeneously resistant and 24 as homogeneously resistant to methicillin (MRSA). The best detection of methicillin-resistance was obtained by two screening techniques 1) on Mueller-Hinton agar with 6 mg oxacillin per litre and incubation for 40 hours at 37 degrees C. The evaluation of commercial test Crystal MRSA ID System proved its high usefulness in proper detection of MRSA and allowed to get results in 4 hours. Disk diffusion with 1 microgram oxacillin disk and incubation for 20 hours at 30 degrees C prove to be the most reliable out of all disc diffusion techniques studied although inferior to screening techniques. PMID- 7996930 TI - [Use of western-blotting technique and computer analysis for comparing cellular antigens of coagulase-negative staphylococci]. AB - Western-Blotting technique and computer programme have been used to analyse cellular antigenic patterns of coagulase-negative staphylococci mainly of S. epidermidis and S. saprophyticus species. It was shown that antigenic pattern among strains of one species was similar. Intra strains differences are mainly quantitative. The qualitative differences concern not quantitatively dominant antigens. The main antigens of S. epidermidis and S. saprophyticus strains were of 28 and 44 kD molecular weight respectively. The antigens of molecular weight around 44, 48, 89 and 105 kD were detected in antigenic extract of strains from different species. Only one of the quantitatively dominant antigen of m. w. 48 kD, was localised in all analysed materials. The method presented here was used for the first time to analyse staphylococcal antigens. Such analysis could be performed not only for bacterial antigens. PMID- 7996931 TI - [In vitro evaluation of susceptibility to selected antibiotics of strains of staphylococcus aureus isolated from purulent skin changes]. AB - Resistance to antibiotics of Staphylococcus aureus strains isolated from purulent skin changes during the years 1987-1991 was investigated. The antibiogram was performed by the disc-diffusion method. Susceptibility to penicillin, ampicillin, cloxacillin, gentamicin, doxycycline, erythromycin, tetracycline, and lincomycin was determined. In investigated material during years 1987-1991 high percentage of resistant strains was found in the case of penicillin (from 70% to 66.2%), cloxacillin (66.6%-86.4%) and tetracycline (50%-66.2%). High and rising in time percentage of strains resistant to ampicillin, erythromycin and cephradine was also found. Increase of resistance was also observed with gentamicin (1987--7.1%, 1991--27%) and doxycycline++ (1987--12.7%, 1989--35.3%, 1991--17.6%), while resistance to lincomycin was keeping on a generally equal level within 20% (1987) to 26% (1991). In 1991 susceptibility of 42 strains of Staphylococcus aureus was tested to cefamandole, cefoperazone, cefotaxime, ceftriaxone, cefuroxime, amikacin and netilmicin. No resistant strains to these antibiotics were found. PMID- 7996932 TI - [Determination of bacteriocinogenic types of strains of Proteus mirabilis]. AB - The study was aimed at determination of bacterioenzymogenic activity of 351 Proteus strains (337 strains of Proteus mirabilis and 14 strains of Proteus Vulgaris) isolated in laboratory of Pediatric Institute of the Medical Academy in Lodz, mostly from urine (222 strains) and feces (99 strains). for determination of bacteriocinogenic properties, 15 index strains "S" were used. Of these, six were from collection of Senior (The University of Dundee Medical School, Scotland) and 9 from own Piatkowski collection (Lodz University). Detection of bacteriocinogenic strains and determination of their activity toward 15 index strains was performed by an own method (15). Out of total 551 strains tested, bacteriocinogenic properties were found in 263 (75%) of strains. Remaining 88 (25%) strains did not inhibit any of the 15 index strains. Sixty-two different types of bacteriocinogenicity were found. The results suggest that bacteriocinogenic typing of Proteus mirabilis strains permits for more precise characterization of properties of these bacteria useful for epidemiological purposes, than by application of other methods. PMID- 7996935 TI - [Serologic diagnosis of infections caused by Borrelia burgdorferi]. AB - This investigation was aimed at selection of optimal serological test for diagnosis of borreliosis occurring at our territory. In our investigations, and indirect immunofluorescence test (IF) was used in which antigen consisted of an American strain of Borrelia burgdorferi B31 and immunoenzymatic test (IE) with an antigen prepared from an European strain. Hundred sixty eight sera were tested, including 138 sera received from patients with suspection of borreliosis or directed for testing because of suspected tick bite. Thirty sera from healthy blood donors served as a control. In 30 out of 138 patients with suspected borreliosis presence of specific antibodies in IF or IE test was detected. In control group positive results were obtained in 4 persons. From our study comparing two tests occurs that more suitable for serodiagnosis of borreliosis on our territory is determination employing as an antigen the European strain of Borrelia burgdorferi. PMID- 7996934 TI - [Occurrence of Helicobacter pylori strains resistant to metronidazole]. AB - This study describes results of in vitro examination of susceptibility to metronidazole of clinical strains of Helicobacter pylori isolated from patients with gastritis. The susceptibility was determined by disc diffusion test. H. pylori was isolated from 44 (67.7%) of patients. Thirty six (81.8%) of the strains were resistant to metronidazole: 17 (85%) from 20 strains isolated from women and 19 (79.2%) from 24 strains isolated from men. This study emphasises the importance of monitoring the drug resistance of H. pylori during therapy. PMID- 7996933 TI - [Infection of burn wound with Acinetobacter baumanii]. AB - This paper describes infection of burn wound with participation of Acinetobacter baumanii in three out of five patients. Species classification of 23 strains of Acinetobacter was performed by application of API 20 NE tests. The profiles obtained through these tests permitted for selection of 8 biotypes. Biotype 00010703 was isolated most frequently. All tested strains of Acinetobacter sp. were susceptible only to netilmicin, norfloxacin, pefloxacin, ofloxacin, ciprofloxacin and imipenem. Out of tested antibiotics, imipenem only was active to all isolated species of bacteria. PMID- 7996937 TI - [Bacteroides melaninogenicus, during Fournier's gangrene]. AB - In two patients (L.C., case No. 5834/215/90 and I.J., case No. 18760/140/91) Fournier's gangrene was diagnosed. From samples of necrotic and stinking secretion, strains of Bacteroides were isolated in anaerobic conditions. Application of metronidazole for treatment and surgical cleaning of the wound resulted in healing of one patient, while the second died. PMID- 7996936 TI - [Effect of subinhibitory doses of some antibiotics on bacteria in vitro]. AB - The study was aimed at observation of influence of subinhibitory doses of selected beta-lactam antibiotics (cefuroxime, ceftazidime, thienamycin) and of ciprofloxacin on morphology and physiology of S. aureus and E. coli. The bacteria were subjected to action of these antibiotics in various subinhibitory concentrations in fluid Mueller-Hinton medium at 37 degrees C for 18 hours, and morphological changes in bacterial cells were observed in light and electronic microscope. In case of E. coli changes appeared as presence of elongated forms, while S. aureus formed giant cells with changes in staining. It was found that intensity of these morphological changes was proportional to concentrations of antibiotics. For determination of influence of tested antibiotics on growth of bacteria they were cultured in the fluid Mueller-Hinton medium containing antibiotics in concentrations of 4, 1 1/4 MIC. The culture lasted for 6 hours, and number of bacterial cells in 1 ml of the medium was periodically determined. Distinct inhibition of growth of bacterial cells was proportional to the used concentrations of antibiotics. Described in this paper morphological changes of bacteria found confirmation in change of their physiology expressed as inhibition of bacterial cell growth. PMID- 7996938 TI - [Identification of toxigenic Clostridium difficile strains isolated from alimentary tract of dogs by PCR]. AB - Twenty eight Clostridium difficile strains were investigated. Eleven strains were toxin A and toxin B gene positive. Four strains were negative for both genes. These results correlate with results of cytotoxicity assay. We identified 13 Clostridium difficile strains toxin A gene positive and toxin B gene negative. PMID- 7996939 TI - [Activity of neutrophilic granulocytes and hematologic picture in rabbits immunized with chlamydia psittaci]. AB - The study was aimed at investigation of selected elements of nonspecific immunity (spontaneous and stimulated NBT reduction test and myeloperoxidase activity of neutrophilic granulocytes) and specific serological response in rabbits immunized twice with suspension of cells of C. psittaci inactivated by formaldehyde. Specific antibodies were detected by complement fixation test and in a titer of 16 or higher were found between 42 and 56 day of the experiment. Statistically significant decrease of myeloperoxidase activity of granulocytes was observed between 14 and 21 day of the experiment, while diminishing values of results of spontaneous NBT reduction test was seen mainly between 35 and 56 day of experiment. The authors conclude that obtained results suggest occurrence of periodical decrease of nonspecific immunity may occur after immunization of animals with inactivated C. psittaci suspension. PMID- 7996941 TI - [Utilization of enzymatic activity in strains of Candida isolated from the vagina for typing and evaluation of pathogenicity]. AB - The study involved 255 strains of Candida isolated from vaginal secretions (194 with symptomatic mycosis and 61 from asymptomatic cases). Most frequently isolated species were Candida albicans, Candida krusei and Candida tropicalis. Determination of lipolytic properties at 30 degrees C and 37 degrees C and proteolytic abilities against albumin and casein permitted for differentiation of strains belonging to Candida albicans and remaining strains of other Candida species. This resulted also in determination of biotypes. Strains of Candida albicans belonged mainly to biotype I, while strains of Candida krusei and Candida tropicalis to biotype IX. Worth attention are results regarding symptomic candidiasis of vagina and enzymatic properties of Candida albicans. Among 145 strains of Candida albicans isolated from cases of symptomatic vaginal mycosis 67 (46.2%) exhibited both lipolytic (at 30 degrees C and 37 degrees C) and proteolytic activities against albumin and casein. At the same time, in asymptomatic mycosis only 14 (33.3%) strains of Candida albicans exhibited same properties. PMID- 7996940 TI - [Isolation and multiplication of rabies virus in cell lines under conditions of routine rabies diagnosis]. AB - Isolation of rabies street virus from brains of animals with rabies was performed on cells of mouse neuroblastoma, infecting cells with suspension of tested brain tissue diluted 1:10, incubating at 37 degrees C in standard incubator (culture in Legroux bottles and Leighton tubes with rubber stoppers) and in 37 degrees C in an incubator with moist chamber and regulated flow of carbon dioxide (Mirco-Well plates, bottom-flat tubes, bottles produced by Nuc, 25-chamber plates produced by Flow). The main conditions for obtaining positive results was proper selection and composition of growing fluid for cells (MEM with Earle's salts produced by Sigma enriched with vitamins, L-glutamine, amino acids and calf fetal fluid) and limited number of passages of tissue after thawing cells from the bank. With passaging neuroblastoma cells are becoming resistant to infection. Growth of cells abd isolation of the virus were possible both in atmosphere containing 5% CO2 and normal air, but application of a standard incubator required higher usage of growth fluids. Positive results were also obtained with infected material stored for a long time. Storage of material at 37 degrees C was making isolation more difficult. Multiplication of stable viruses on BHK, neuroblastoma and Vero cells permitted for obtaining antigens for serological diagnosis of rabies in vitro. PMID- 7996942 TI - [It is possible to save a lot of money and not affect the patients]. PMID- 7996943 TI - [Care of the medical community is underestimated]. PMID- 7996944 TI - [Rheumatologic rehabilitation--a resource!]. PMID- 7996945 TI - [Resuscitation or not? A vital but difficult situation]. PMID- 7996946 TI - [Do we follow recommendations of the National Board of Health and Welfare on resuscitation? The patient should decide]. PMID- 7996947 TI - [Ethical views on resuscitation. Formal guidelines for do-not-resuscitate orders in Sweden]. PMID- 7996948 TI - [Tips about new discoveries on TIPS. Better and better treatment of portal hypertension and esophageal and gastric varices]. PMID- 7996951 TI - [Nature's solution of the communication problem resulted in Nobel Prize. Significance of G-proteins for signal transmission in cells]. PMID- 7996950 TI - [The man behind the syndrome: Erik A. von Willebrand. He discovered the cause of an earlier unknown form of hemorrhage]. PMID- 7996949 TI - [Increased number of knife assaults inspite of the legislation. Record of injuries among 399 patients]. AB - From January 1985 to September 1993, 399 patients (368 men and 31 women), median age 28 years (mean 31.1, range 16-71 years), were admitted with stab wounds due to assault. The number of stab wounds per patient was one (N = 268 patients), two (N = 63), three (N = 31), four (N = 15), five (N = 7), or more than five (N = 15). The series as whole (N = 399) accounted for 543 sites of injury. Upper extremity wounds were the most frequent (35 per cent); of 188 arm injuries, 60 per cent were in the left arm. The next most frequent site was the head and neck region (N = 105; 12 per cent), followed by the chest (N = 75; 14 per cent), abdomen (N = 66;12 per cent), lower extremities (N = 59;11 per cent), back (N = 48;9 per cent), and the male genitalia (N = 2;0.4 per cent). Ninety-five major operations were performed in 74 patients. Seven patients died, and 40 had somatic or cosmetic life-time sequelae. PMID- 7996952 TI - [Transfemoral treatment of abdominal aortic aneurysm. A new way to carry on vascular surgery]. PMID- 7996953 TI - Weapons intended to blind. PMID- 7996954 TI - HIV testing in prison: what's the controversy? PMID- 7996955 TI - Superoxide dismutase and ALS. PMID- 7996956 TI - Shifting indications for hysterectomy: nature, nurture, or neither? PMID- 7996957 TI - Gene therapy for arterial disease. PMID- 7996958 TI - Randomised trial of endoscopic stenting versus surgical bypass in malignant low bileduct obstruction. AB - The development of non-surgical techniques for the relief of malignant low bileduct obstruction has cast doubt on the best way of relieving jaundice, particularly in patients fit for surgery whose life expectancy is more than a few weeks. We did a randomised prospective controlled trial comparing endoscopic stent insertion and surgical biliary bypass in patients with malignant low bileduct obstruction. 204 patients were randomised (surgery 103, stent 101); 3 subsequently proved to have benign disease and were excluded, leaving 101 surgical and 100 stented patients for assessment. Technical success was achieved in 94 surgical and 95 stented patients, with functional biliary decompression obtained in 92 patients in both groups. In stented patients, there was a lower procedure-related mortality (3% vs 14%, p = 0.01), major complication rate (11% vs 29%, p = 0.02), and median total hospital stay (20 vs 26 days, p = 0.001). Recurrent jaundice occurred in 36 stented patients and 2 surgical patients. Late gastric outlet obstruction occurred in 17% of stented patients and 7% of the surgical group. Despite the early benefits of stenting there was no significant difference in overall survival between the two groups (median survival: surgical 26 weeks; stented 21 weeks; p = 0.065). Endoscopic stenting and surgery are effective palliative treatments with the former having fewer early treatment related complications and the latter fewer late complications. PMID- 7996960 TI - Effect of nitrogen dioxide and sulphur dioxide on airway response of mild asthmatic patients to allergen inhalation. AB - Air pollution may enhance the airway response of asthmatic subjects to allergen inhalation. To test the hypothesis that sulphur dioxide and nitrogen dioxide alone or in combination could have a contributory role, we have studied the effect of 6 h exposure to air, 200 parts per billion (ppb) sulphur dioxide, 400 ppb nitrogen dioxide, and the two gases together on the airway response to inhaled allergen in ten volunteers with mild atopic asthma. The subjects were exposed to the gases in random order at weekly visits, then challenged with pre determined concentrations of Dermatophagoides pteronyssinus allergen 10 min after each exposure. The forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC), and cumulative breath units (CBU) of D pteronyssinus allergen required to produce a 20% fall in FEV1 (PD20FEV1) were measured after each exposure. Compared with air, neither sulphur dioxide nor nitrogen dioxide nor the combination significantly altered FEV1 or FVC. Although the decreases in PD20FEV1 after exposure to each agent alone were not significant (41.2%, p = 0.125 after nitrogen dioxide; 32.2%, p = 0.506 after sulphur dioxide) the decrease after exposure to the combination was significant (60.5 [SE 8.1]%, p = 0.015). Exposure to a combination of sulphur dioxide and nitrogen dioxide in concentrations that could be encountered in heavy traffic enhances the airway response to inhaled allergen, possibly as a result of previous airway inflammation. PMID- 7996959 TI - Clinical significance of absent or reversed end diastolic velocity waveforms in umbilical artery. AB - Doppler ultrasound provides a non invasive method to assess fetal haemodynamics. We looked at the outcome of doppler velocimetry of the umbilical artery in three groups of pregnancies: those with positive end diastolic velocities (PED; n = 214), absent end diastolic velocities (AED; n = 178) and reversed end diastolic velocities (RED; n = 67). We collected our data from 9 European centers. Logistic regression showed that compared with pregnancies with hypertension only, pregnancies complicated by intra uterine growth retardation (IUGR) had a higher risk of developing absent or reversed end diastolic velocity waveforms (ARED) flow. ARED flow in the umbilical artery (odds ratio: OR = 3.1). Pregnancies complicated by both IUGR and hypertension had an even higher risk (OR = 7.4). Maternal age and smoking habits did not influence the risk of developing ARED flow. The overall perinatal mortality rate was 28%. Significantly more neonates in the ARED flow group needed admittance to the neonatal intensive care unit (PED group 60%, AED group 96%, RED group 98%). The OR for perinatal mortality in pregnancies complicated by AED flow was 4.0 and in RED flow was 10.6, compared with PED flow, even after adjustment for menstrual age. ARED flow in the umbilical artery did not influence the risk of respiratory distress syndrome or necrotising enterocolitis of the neonate, but ARED flow significantly influenced the risk of cerebral haemorrhage, anaemia, or hypoglycaemia. We advise that pregnancies complicated by IUGR and/or hypertension should be followed up with doppler velocimetry to trace utero-placental problems as early as possible. A caesarean section is recommended in all pregnancies complicated by ARED flow if the gestational age and predicted neonatal weight can be handled by the local neonatal intensive care unit. PMID- 7996961 TI - Non-cytolytic CD8 T-cell anti-HIV responses in primary HIV-1 infection. AB - Acute HIV infection is accompanied by a sharp rise in virus titres that soon fall, but the role of humoral and cellular immunity is not clear in the control of initial virus replication. We have found seven HIV-1 infected subjects who had CD8 T-cell non-cytolytic anti-HIV activity in plasma many months before neutralising antibodies can be detected. We observed an inverse relation between the extent of this CD8 cell response and the level of plasma viraemia in some subjects. These results suggest that a cellular immune response controls viral replication soon after HIV infection. PMID- 7996962 TI - Greatly increased luminal nitric oxide in ulcerative colitis. AB - A role for nitric oxide (NO) in ulcerative colitis has been suggested because mucosal NO synthase activity, measured by indirect assays, is increased in this disorder. We directly measured luminal NO in the colons of twelve controls and six patients with active ulcerative colitis. During colonoscopy, gas was aspirated from different parts of the colon and immediately analysed by a chemiluminescence technique. NO concentrations were more than 100 times higher in the patients than in the controls. Luminal NO is rapidly and easily measurable and may be used to monitor inflammatory bowel disease. PMID- 7996963 TI - Goitrous endemic in Guinea. AB - We identified a major goitrous area in the Republic of Guinea, characterised by an overall goitre prevalence of 70% in adults. Thyroid swelling was sometimes present at birth and affected 55% of schoolchildren. A difference between sexes appeared at puberty. Endemic cretinism, mainly in its myxoedematous form, was found in about 2% of goitrous patients. In this region, iodine deficiency is the primary causative factor (median urinary concentrations of 16 micrograms/L, and in 69% of inhabitants below the critical threshold of 20 micrograms/L). The diet contained substantial amounts of thiocyanate anions (median 6 mg/L in urine and in 27%, more than 10 mg/L) likely to further depress iodine bioavailability. Other dietary compounds, notably flavonoids were suspected to contribute. Overall nutritional and general health appeared satisfactory. The affected population is borderline euthyroid with a trend towards hypothyroidism in protracted disease. This area of Guinea may be regarded as the epicentre of the west African endemic and as one of the most severely goitrous regions ever described, requiring urgent public health measures. PMID- 7996964 TI - Enzyme replacement treatment in type 1 and type 3 Gaucher's disease. AB - The development of intravenous enzyme-replacement treatment for Gaucher's disease has changed life expectancy in cases without neurological involvement (type 1). The effects in patients with neurological involvement are unknown. We treated 12 Italian patients, types 1 (9) and 3 (3), with intravenous alglucerase: 70-120 IU/kg per month for type 3 and 30-60 IU/kg per month for type 1. Maintenance infusions were biweekly in patients without neurological symptoms, whereas in one symptomatic type 3 patient, infusion was weekly. All patients improved; a resumption of growth in children with growth retardation was observed and spleen and liver reduced in size. In one type 3 patient, a bone callus formed during treatment and enabled the patient to walk. Laboratory tests showed rapid increase of haemoglobin in anaemic patients, and a slower response in patients with thrombocytopaenia. In 4 patients there was temporary hypocalcaemia immediately after the beginning of treatment. Neurological symptoms were present in 1 of the type 3 patients, and electroencephalogram was abnormal in another. After 2 years of treatment, the patient with symptoms showed an improvement of psychomotor skills and of IQ from 50 to 60. Genotype analysis showed a high frequency of the 1448C mutation (54.5%). The 9 patients carrying this allele came from Italian regions which in the past had been invaded from north Europe and Scandinavia. Enzyme replacement in Gaucher's type 1 can also be effective at low doses and even with a 2-week interval between infusions. This makes treatment cheaper, and reduces hospital stay for patients. PMID- 7996965 TI - Clinical data systems, Part 3: Development and evaluation. PMID- 7996966 TI - Rwanda: a case of demographic entrapment. PMID- 7996967 TI - Medics versus managers. PMID- 7996969 TI - Patient-to-patient HIV transmission trial. PMID- 7996968 TI - Renewed UN drive against AIDS. PMID- 7996970 TI - Detention and enforced feeding. PMID- 7996971 TI - Proctoclysis for hydration of terminal cancer patients. PMID- 7996972 TI - Detecting permethrin on treated bed nets. PMID- 7996973 TI - Warm chain for breastfeeding. PMID- 7996974 TI - Warm chain for breastfeeding. PMID- 7996975 TI - Warm chain for breastfeeding. PMID- 7996976 TI - Hair loss associated with lamivudine. PMID- 7996977 TI - Warm chain for breastfeeding. PMID- 7996978 TI - Interferon beta-1b. PMID- 7996979 TI - Parapertussis infection followed by pertussis infection. PMID- 7996980 TI - Withdrawal bleeding and endometrial safety. PMID- 7996981 TI - Sumatriptan-induced chest pain. PMID- 7996983 TI - Primary care. PMID- 7996982 TI - Insulin resistance or insulin deficiency as precursor of non-insulin-dependent diabetes mellitus. PMID- 7996984 TI - Primary care. PMID- 7996985 TI - Primary care. PMID- 7996986 TI - Primary care. PMID- 7996987 TI - Breast cancer and organochlorines. PMID- 7996988 TI - Mesalazine during pregnancy. PMID- 7996989 TI - Resistance to activated protein C and risk of premature myocardial infarction. PMID- 7996990 TI - Video-game epilepsy. PMID- 7996991 TI - Video-game epilepsy. PMID- 7996992 TI - Dentatorubral-pallidoluysian atrophy and Haw River syndrome. PMID- 7996993 TI - Persistent asthma after acute inhalation of organophosphate insecticide. PMID- 7996994 TI - Essence of stress. PMID- 7996995 TI - The politics of masturbation. PMID- 7996997 TI - Enzymes as catalysts of autoimmunity. PMID- 7996996 TI - Fat, female, and poor. PMID- 7996998 TI - Langerhans cell histiocytosis: where do we go from here? PMID- 7996999 TI - Does diet or alcohol explain the French paradox? AB - The low rate of coronary heart disease (CHD) in France compared with other developed countries with comparable dietary intake has been called the French paradox. We explored this paradox by looking at alcohol, diet, and mortality data from 21 developed, relatively affluent countries in the years 1965, 1970, 1980, and 1988. We assessed wine, beer, and spirits intake separately. France had the highest wine intake and the highest total alcohol intake, and the second lowest CHD mortality rate. In univariate analyses, ethanol in wine was slightly more inversely correlated with CHD than total wine volume. In multivariate analyses, animal fat tended to be positively correlated, and fruit consumption inversely correlated, with CHD. Beer and spirits were only weakly inversely correlated with CHD. The strongest and most consistent correlation was the inverse association of wine ethanol with CHD. However, wine ethanol was unrelated to total mortality. We conclude that ethanol, particularly wine ethanol, is inversely related to CHD but not to longevity in populations. Although light to moderate alcohol consumption may improve longevity, alcohol abuse--which sharply reduces longevity--is correlated with average alcohol consumption in populations. Thus, while the risk/benefit ratio varies for individuals, the use of alcohol for cardioprotective purposes should not be encouraged as a public health measure. PMID- 7997000 TI - Controlled study of malathion and d-phenothrin lotions for Pediculus humanus var capitis-infested schoolchildren. AB - Anecdotal reports have suggested that reduced efficacy of pediculicides against Pediculus humanus capitis could be related to resistance to treatments. Ovicidal and pediculicidal activities of 0.5% malathion and 0.3% d-phenothrin lotions were tested in an experimental model of P humanus capitis grown on rabbits to ensure that the two treatments were pharmacologically equipotent. We then did a randomised controlled trial in which the lotions were administered to 193 P humanus capitis-infested schoolchildren (malathion, 95; d-phenothrin, 98). Success rate was defined as the absence of both live lice and viable nits. Before treatment, live lice were collected and subjected to a pediculicidal test. Pharmacological tests showed 100% killing of the rabbit-grown nits and lice after exposure to both pediculicides. On day 1 of the controlled trial, the success rate was 92% in the malathion group (95% CI, 0.86-0.97) and 40% in the d phenothrin group (0.30-0.49) (p < 0.0001); on day 7, it was 95% in the malathion group (0.90-0.99) and 39% in the d-phenothrin group (0.29-0.48, p < 0.0001). Malathion was also significantly more active in the pediculicidal tests compared to d-phenothrin and control. These results suggest an acquired resistance to d phenothrin in the schoolchildren tested, since all other conditions of the administration of insecticides were standardised. PMID- 7997001 TI - Controlled trial of three approaches to the treatment of severe malnutrition. AB - Domiciliary treatment of severely malnourished children could have economic and practical advantages over other methods. We compared three approaches in a controlled trial. 437 children in Dhaka (< 60% weight-for-height, and/or oedema) aged 12-60 months were sequentially allocated to treatment as inpatients, to day care, or to care at home after one week of day-care. Institutional and parental costs incurred to reach 80% weight-for-height were compared. Costs for inpatient, day-care, and at-home groups averaged 6363, 2517, and 1552 taka (60 taka = UK pound 1). Mortality was low (< 5%) in all three groups. Day-care treatment approached inpatient care for speed of recovery at less than half the cost, but it was unpopular with parents. The at-home group took significantly longer to attain 80% weight-for-height than the other groups, but did so at the lowest average cost. Parental costs were highest for the at-home group as no food supplements were provided; nevertheless this was the most popular option. We conclude that at-home management of severely malnourished children after 1 week of inpatient care is a cost-effective strategy. PMID- 7997002 TI - Effect of domestic concentrations of nitrogen dioxide on airway responses to inhaled allergen in asthmatic patients. AB - Nitrogen dioxide is a common indoor pollutant. In the light of suggestions that outdoor air pollution can harm people with asthma, we investigated the effect of 1 h exposures to domestic concentrations of nitrogen dioxide on the airway response to house-dust mite (HDM) allergen in ten patients with mild asthma. Each subject breathed air, 100 ppb nitrogen dioxide, or 400 ppb nitrogen dioxide for 1 h, in double-blind, random order, then immediately underwent a fixed-dose HDM challenge. Baseline forced expiratory volume in 1 s (FEV1) was not affected by any of the gas mixtures. The mean early asthmatic response (maximum percentage change in FEV1 during first 2 h after challenge) was -14.62% (SD 8.03) after air, -14.41% (7.86) after 100 ppb nitrogen dioxide, and -18.64% (7.28) after 400 ppb nitrogen dioxide. The difference between air and 400 ppb (-4.01%) was significant (95% CI -1.34 to -6.69%, p < 0.009), but those between air and 100 ppb and between 100 and 400 ppb were not (0.21 [-3.10 to 3.53]% and -4.23 [-8.75 to 0.29]%). The mean late asthmatic response (maximum percentage change in FEV1) to challenge after air was -2.85% (3.95), after 100 ppb nitrogen dioxide -7.76% (6.92), and after 400 ppb -8.13% (6.64). The difference in means between the air and 400 ppb exposures was significant (-5.28 [-0.73 to -9.83]%, p < 0.02) but those between air and 100 ppb (-4.90 [-10.60 to 0.78]%) and 100 and 400 ppb (0.37 [3.06 to 3.80]%) were not. These findings suggest that nitrogen dioxide, at concentrations encountered in the home environment, can potentiate the specific airway response of patients with mild asthma to inhaled HDM allergen, although the effect is small. PMID- 7997003 TI - Hypercoagulable states: molecular genetics to clinical practice. AB - Several physiological antithrombotic proteins--including antithrombin, protein C, protein S, tissue factor pathway inhibitor, and components of the fibrinolytic system--act as inhibitors at strategic sites in the coagulation cascade to maintain normal blood fluidity under normal circumstances. The molecular basis of specific inherited hypercoagulable states has been recently elucidated. With the description of resistance to activated protein C, which is the commonest coagulation defect associated with thrombophilia, a specific primary hypercoagulable state can be identified in over 50% of patients with thrombophilia. Although the prevalence in the normal population of some "prothrombotic" mutations is remarkably high, most affected individuals do not have clinical thrombotic complications, so it is likely that clinically apparent hypercoagulable states result from multigene interactions, and that clinical episodes of thrombosis are precipitated by acquired prothrombotic insults in patients with an inherited predisposition to thrombosis. PMID- 7997004 TI - Acute laryngeal obstruction. PMID- 7997005 TI - Why monitor peak vancomycin concentrations? AB - Peak and trough serum concentrations are routinely measured to monitor vancomycin therapy. Optimal therapy depends upon maintaining a concentration above that necessary for antibacterial activity and is therefore determined by the trough concentration. I determined the post dose increases in serum drug concentrations in routine clinical practice in adult patients without renal failure. Mean increases of 16.6 mg/L (SD 6.1) (peak samples collected 1 h post infusion) were measured from 165 paired samples. The results suggest that as long as trough concentrations do not exceed 15 mg/L, peak levels will not exceed normally accepted safe concentrations, and therefore do not need to be measured. PMID- 7997006 TI - Caravaggio's "Il Amore Dormiente": a sleeping cupid with juvenile rheumatoid arthritis. PMID- 7997007 TI - Is it possible to have an unconscious thought? PMID- 7997008 TI - Out goes the Surgeon General. PMID- 7997009 TI - American Society of Hematology meeting. PMID- 7997010 TI - Biophysical properties of the aorta. PMID- 7997011 TI - Scandinavian simvastatin study (4S) PMID- 7997012 TI - Scandinavian simvastatin study (4S) PMID- 7997013 TI - Scandinavian simvastatin study (4S) PMID- 7997014 TI - Scandinavian simvastatin study (4S) PMID- 7997015 TI - Scandinavian simvastatin study (4S) PMID- 7997016 TI - Scandinavian simvastatin study (4S) PMID- 7997017 TI - Scandinavian simvastatin study (4S) PMID- 7997018 TI - Short-course cimetidine and survival with colorectal cancer. PMID- 7997020 TI - Intracranial meningiomas among Nagasaki atomic bomb survivors. PMID- 7997019 TI - De-novo mutations of the RET proto-oncogene in Hirschsprung's disease. PMID- 7997021 TI - Necrotising fasciitis. PMID- 7997022 TI - Necrotising fasciitis. PMID- 7997023 TI - Mother to child transmission of zidovudine-resistant HIV-1. PMID- 7997024 TI - "Sporadic" motoneuron disease due to familial SOD1 mutation with low penetrance. PMID- 7997027 TI - The Culyer report. PMID- 7997026 TI - The Culyer report. PMID- 7997028 TI - Experiment and observation. PMID- 7997029 TI - Poliomyelitis in Namibia. PMID- 7997030 TI - Preserving the ancients with vermillion. PMID- 7997031 TI - Malignant pleural mesothelioma associated with exposure to tremolite. PMID- 7997032 TI - Clarithromycin for atypical mycobacterial lymphadenitis in non-immunocompromised children. PMID- 7997033 TI - Urine culture in the elderly. PMID- 7997034 TI - Urine culture in the elderly. PMID- 7997035 TI - Urine culture in the elderly. PMID- 7997036 TI - Late-onset fatal neurological toxicity of fludarabine. PMID- 7997037 TI - Stroke scoring systems. PMID- 7997038 TI - Stroke scoring systems. PMID- 7997039 TI - Stroke scoring systems. PMID- 7997040 TI - Percutaneous transluminal coronary angioplasty without radiographic contrast agent. PMID- 7997041 TI - Localisation of carcinoid tumour with radiolabelled octreotide and intraoperative gamma detection. PMID- 7997042 TI - Use of fluid attenuated inversion recovery sequence in magnetic resonance imaging. PMID- 7997043 TI - Enhanced ArF laser absorption in a collagen target under ablative conditions. AB - The time-resolved transmission of collagen targets during ArF excimer laser ablation has been measured. The transmitted excimer pulse measurements demonstrate enhanced media attenuation that is a nonlinear function of incident laser fluence. Forward scattering of the transmitted pulse has been assessed to be a negligible contributor to the observed phenomena. Results of pump/probe interrogation of the ablation site indicate that the onset of enhanced attenuation occurs on the time course of the ablating laser pulse and persists for times on the order of hundreds of microseconds. PMID- 7997045 TI - Phthalocyanine mediated photodynamic thrombosis of experimental corneal neovascularization: effect of phthalocyanine dose and irradiation onset time on vascular occlusion rate. AB - The aim of this study was to evaluate the possible influence of phthalocyanine dose and of time interval between phthalocyanine injection and irradiation commencement on the rate of experimental corneal neovascularization photodynamic thrombosis in albino rabbits. New corneal vessels were irradiated with a diode laser (670 nm, 2 mW) after the intravenous injection of chloroaluminum sulfonated phthalocyanine. Different animals were irradiated either 5 min after the injection of different phthalocyanine doses (3, 6, 8, 12, or 14 mg/kg), or at different times (5 min, 24 h, or 58 h) after a standard phthalocyanine dose (3 mg/kg) injection. Irradiation time necessary for vascular occlusion was recorded. Decrease of phthalocyanine dose as well as delay of irradiation onset resulted in a statistically significant increase of irradiation time. Electron and light histological examination revealed platelet thrombi inside irradiated corneal new vessels. Damage in the vascular endothelial cell membrane and in intercellular contact structure was noted, leading to disorganization of the endothelial cells layer and death of most endothelial cells. These results indicate that both early commencement of irradiation after phthalocyanine injection and phthalocyanine dose increase accelerate the rate of phthalocyanine mediated corneal neovascularization photodynamic thrombosis. Thrombosis seems to result from photochemically induced vascular endothelial cell damage. PMID- 7997044 TI - Retinal and choroidal vessel closure using phthalocyanine photodynamic therapy. AB - Chloro-aluminum sulfonated phthalocyanine (CASPc) is a photoactive dye capable of generating photochemical reactions when excited with 675 nm light. We used CASPc to produce photochemical closure of retinal medullary ray vessels and choroidal vessels in normal rabbits. Irradiation prior to CASPc injection produced no photographic, angiographic, or histologic lesions in any eyes. Identical irradiation of medullary ray and choroidal vessels after CASPc injection produced complete vessel closure in all eyes. Histopathologic examination showed marked thrombosis of medullary ray and choroidal vessels, with minimal damage to contiguous tissues including the neurosensory retina. We conclude that CASPc can produce profound closure of normal retinal and choroidal vessels with minimal deleterious effect on surrounding tissues. PMID- 7997046 TI - Mechanisms of intraocular photodisruption with picosecond and nanosecond laser pulses. AB - Nd:YAG laser photodisruption with nanosecond (ns) pulses is an established method for intraocular surgery. In order to assess whether an increased precision can be achieved by the use of picosecond (ps) pulses, the plasma size, the shock wave characteristics, and the cavitation bubble expansion after optical breakdown with ps- and ns-laser pulses were investigated by time-resolved photography and acoustic measurements. Nd:YAG laser pulses with a duration of 30 ps and 6 ns, respectively, were focused into a water-filled glass cuvette. Frequency doubled light from the same laser pulses was optically delayed between 2 ns and 136 ns and used as illumination light source for photography. Since the individual events were well reproducible, the shock wave and bubble wall position could be determined as a function of time. From the slope of these r(t) curves, the shock wave and bubble wall velocities were determined, and the shock wave pressure was calculated from the shock velocity. The plasma size at various laser pulse energies was measured from photographs of the plasma radiation. The breakdown thresholds at 30 ps and 6 ns pulse duration were found to be 15 microJ and 200 microJ, respectively. At threshold, ps-plasmas are shorter than ns-plasmas, but at the same pulse energy they are always approximately 2.5 times longer. The initial shock pressures were 17 kbar after ps-pulses with an energy of 50 microJ, and 21 kbar after 1 mJ ns-pulses. The pressure amplitude decayed much faster after the ps-pulses. The maximum expansion velocity of the cavitation bubble was 350 m/s after a 50 microJ ps-pulse, but 1,600 m/s after a 1 mJ ns-pulse. The side effects of intraocular microsurgery associated with shock wave emission and cavitation bubble expansion can be considerably reduced by the use of ps-pulses, and new applications of photodisruption may become possible. PMID- 7997047 TI - Intraocular microsurgery with a picosecond Nd:YAG laser. AB - We investigated the use of picosecond Nd:YAG laser pulses for intraocular microsurgery. With a pulse duration of 100 picoseconds, only 70 microJ of pulse energy is required to consistently produce optical breakdown in the deep vitreous. This pulse energy is nearly two orders of magnitude less than the typical pulse energies used in conventional (nanosecond) photodisruptors. The reduced pulse energy results in a smaller zone of tissue damage, an important consideration when operating close to the retina or other sensitive ocular structures. Efficient cutting action is achieved by applying multiple pulses at a moderately high repetition rate of 50-200 Hz. An in vitro model was developed to assess axial confinement of picosecond photodisruption. In vivo vitreous membrane surgery was performed in experimental rabbit eyes to demonstrate a potential clinical application of picosecond laser-induced optical breakdown. PMID- 7997049 TI - Light distribution of ocular endophotocoagulator probes and its surgical implications. AB - Ophthalmic endophotocoagulator probe cone angle affects the spot size, working distance, laser output power requirement, tissue exposure time, and uniformity of tissue irradiance, which all affect ease and safety of clinical use. The cone angle and irradiance distribution of several ophthalmic endophotocoagulator delivery systems were studied by directing the laser energy emitted by them on a CCD video sensor at several angles of incidence. The irradiances followed a Gaussian distribution. The measured irradiances were compared to a mathematical model of tissue irradiance that adjusted for the cone angle, probe-tissue distance, and angle of incidence. Using this model, laser irradiances produced by endophotocoagulator probes can be estimated under a wide variety of conditions. At highly oblique angles of incidence, wide-angle probes produce unexpectedly higher and uneven tissue irradiance. When numerous characteristics are considered, probes with a cone angle in the range of 10 degrees have many advantages over narrower or wider angle probes. PMID- 7997048 TI - Dynamic reflectometer for control of laser photocoagulation on the retina. AB - In retinal laser photocoagulation, constant exposure parameters do not result in identical lesions. This lack of reproducibility increases the rate of complications from over- or undertreatment and inhibits determination of the optimal treatment endpoints for different retinal disorders. To this end, a feedback-controlled photocoagulator could make retinal photocoagulation a safer, more reproducible, and faster procedure. A dynamic confocal reflectometer was integrated into a slit lamp laser delivery system. Real-time reflectance changes on the retinas of pigmented rabbits were obtained by monitoring the increasing back-scattered light of the coagulating beam during argon laser photocoagulation. Reproducible temporal reflectance patterns were measured that correlated with ophthalmoscopically assessed lesion intensity independent of the exposure parameters, the transparency of the optical media, and the focusing conditions. As a step toward the development of a feedback-controlled photocoagulator, the confocal reflectometer has been proven in animal trials closely resembling clinical practice. PMID- 7997050 TI - Erbium-YAG and holmium-YAG laser ablation of the lens. AB - Er-YAG (2.9 microns, 200 microseconds pulsewidth) and Ho-YAG (2.12 microns, 250 microseconds pulsewidth) lasers were used to irradiate bovine crystalline lenses. Mass ablated increased with increasing fluence for both lasers and was greater for the Er-YAG than the Ho-YAG laser at all fluences. The mass loss vs. fluence curve was nonlinear for the Er-YAG and linear for the Ho-YAG laser. Ablation threshold was lower for the Er-YAG. Grossly, the Er-YAG laser produced less charring and expressed fewer, smaller tissue pieces than the Ho-YAG. Scanning electron microscopy indicated that the Er-YAG produced smoother walled craters. The Ho-YAG laser produced more dessicated and disrupted craters. The Er-YAG radiation, delivered by fiberoptic probes, may provide a method of performing minimally invasive cataract surgery. PMID- 7997051 TI - Application of the potassium-titanyl-phosphate laser during extraocular muscle surgery: technique and histopathology. AB - We determined laser parameters and delivery system requirements for successful use of the potassium-titanyl-phosphate (KTP) laser for strabismus surgery and its histopathologic effect on extraocular muscle, tendon, sclera, and cornea of human and rabbit eyes. Enucleated cadaver eyes and exenterated rabbit orbital contents were used. Using a 200-microns fiberoptic tip delivery system, varying laser energies were used to perform muscle insertion site and corneal damage, tenotomies, and myotomies. Pulse durations of 0.5 second and energies above 0.8 watt were needed for tenotomy or myotomy. No damage to the surrounding tissues or sclera was observed with laser tenotomy or myotomy performed 0.5 mm from the insertion site. Energy above 0.8 watt applied directly caused full thickness disruption. In comparison to scissor myotomy, the laser provided charring of the superficial tissues. This study shows that the KTP laser can be safely and accurately used for extraocular muscle tenotomy or myotomy. PMID- 7997052 TI - Dynamics of shock waves and cavitation bubbles generated by picosecond laser pulses in corneal tissue and water. AB - Time-resolved flash photography was used to investigate the dynamics of shock waves and cavitation bubbles generated by picosecond optical breakdown in bovine corneal tissue and water. A picosecond Nd:YLF laser was employed. A rapid decay of the shock waves was observed in both materials, with similar temporal characteristics, indicating that water serves as a good model for shock wave studies. In contrast, differences in the cavitation bubble dynamics were found between cornea and water, which are related to differences in the mechanical and thermal properties of the two media, suggesting that water should not be used to model cavitation dynamics in cornea. The experimental results also suggest that the efficiency of intrastromal ablation may be increased by using short pulses and moderate pulse energies in order to avoid the creation of large cavitation bubbles. The experiment indicates that the optimum laser repetition rate for intrastromal ablation is between 1 and 5 kHz. PMID- 7997054 TI - Novel Treatments of Age-Related Brain Disorders. Proceedings of a conference. Heidelberg, Germany, September 9-11, 1993. PMID- 7997053 TI - Rate-dependent, nonlinear photoablation of ocular tissue at 308 nm. AB - To quantify the dependence on pulse repetition rate of 308 nm laser ablation in ocular tissue and elucidate the photoablation mechanisms involved, 85 full thickness ab interno sclerostomies were created in six human donor eyes using an 800-microns-diameter quartz optical fiber. A laser pulse duration of 135 ns, fluence of 31 mJ/mm2, and a fixed repetition rate between 5 and 40 Hz were used for 38 sclerostomies; the remaining 47 sclerostomies were completed at various laser settings during initial experimentation. Surprisingly, the numbers of pulses required for complete penetration of the optical fiber through the fixed tissue thickness were not constant as expected but decreased nonlinearly with increasing repetition rate. This demonstrates that the 308 nm excimer laser cuts ocular tissue significantly more rapidly per pulse at higher repetition rates. To explain this nonlinearity, we propose a composite ablation mechanism composed of photochemical, thermal, mechanical, and optical effects in varying proportions. PMID- 7997055 TI - Brain aging: a risk factor of neurodegenerative disorders and a target for therapeutic intervention. PMID- 7997056 TI - Neurodegeneration, Alzheimer's disease, and beta-amyloid toxicity. AB - In its majority, Alzheimer's disease is sporadic and with late onset. Therefore, age-related disturbances in cellular metabolism may come into focus with respect to the etiopathogenesis of this neurodegenerative disorder. As a possible primary abnormal event in sporadic Alzheimer's disease, a desensitization of the neuronal insulin receptor and the subsequent deficits in ATP and acetylcholine are discussed with its impact on protein processing in general and beta-amyloid formation in particular, and neurotoxicity of the latter. PMID- 7997057 TI - Neurotransmitter receptor plasticity in aging. AB - Neurotransmitter receptor plasticity is an important part of the compensatory processes by which the central nervous system adapts to pathological insult, long term exposure to drugs or neuronal loss with advanced age. Receptor plasticity can be manifest as changes in the number of receptors (i.e., up- or down regulation), changes in expression of mRNA for discrete receptor proteins, or alterations in receptor coupling to signal transduction systems. Evidence exists for impaired plasticity of neurons in the aged brain, which results in decreased ability to adjust to changes in their environment. However, such data are highly dependent on the neurotransmitter examined, the stimulus for receptor regulation and the animal model chosen for study. For example, senescent rats show an age related impairment of muscarinic receptor up- or down-regulation after long-term exposure to cholinergic drugs. Thus, young rats exposed to chronic (three weeks) intracerebroventricular infusions of methylatropine or oxotremorine exhibit compensatory changes in the density of muscarinic receptors in frontal cortex and hypothalamus. In contrast, 3H-QNB binding is unaltered in the same brain regions of identically treated senescent rats. Similar observations of impaired muscarinic receptor plasticity in senescent animals have been confirmed by other investigators. Age-related differences in coupling of brain muscarinic receptors to G-proteins and in muscarinic receptor-stimulated phosphoinositide hydrolysis have also been reported. Interestingly, neuropeptides such as neurotensin, cholecystokinin and VIP can potentiate carbachol-stimulated phosphoinositide hydrolysis in frontal cortex of both young and aged rats. This adds another level at which cholinergic neurotransmission may be modulated in senescent animals. Potential age-related differences in the effects of chronic drug treatments or experimental brain lesions on muscarinic receptor coupling to second messenger systems or on expression of mRNA for particular muscarinic receptors are currently unknown. Hence, it is possible that senescent animals may show additional deficiencies in plasticity of muscarinic receptor mediated signal transduction or expression of muscarinic receptors subtypes. PMID- 7997058 TI - Cholinergic and serotonergic stimulation of phosphoinositide hydrolysis is decreased in Alzheimer's disease. AB - Agonist-stimulated phosphoinositide (PPI) hydrolysis is a major signal transduction pathway in brain. These studies investigated neurotransmitter stimulated PPI hydrolysis in postmortem human brain. Preliminary studies using rat brain suggested that moderate postmortem delay has little effect on PPI hydrolysis and that human tissue might be reliably studied for differences in receptor-PLC coupling. Studies in human brain membranes (frontal cortex) indicated that the time course for GTP gamma S and carbachol/GTP gamma S stimulated PPI hydrolysis was linear for at least 20 min. GTP gamma S-stimulated [3H]inositol phosphate (InsP) formation was enhanced by carbachol (232%) and 5 Hydroxytryptamine (5HT-147%). SAX-HPLC separation of [3H]inositol polyphosphates indicated that the major isomer of inositol trisphosphate (InsP3) was Ins(1.4.5)P3, the expected product of PtdIns(4,5)P2 hydrolysis. Ca2+ increased PPI hydrolysis progressively from 100 nM through 50 microM and synergistically enhanced carbachol/GTP gamma S stimulation. Comparisons of age-matched controls with Alzheimer's patients indicated that GTP gamma S, carbachol/GTP gamma S, and 5HT/GTP gamma S-stimulation of PPI hydrolysis is reduced approximately 50% in membranes prepared from Alzheimer's patients. Ca2+ of PPI hydrolysis was not different between controls and Alzheimer's patients suggesting that muscarinic cholinergic and serotonergic receptors are uncoupled from PLC in Alzheimer's disease. These studies indicate that there are changes in cholinergic and serotonergic signal transduction in Alzheimer's disease. Further, this method can be used to study signal transduction events in postmortem human brain. PMID- 7997059 TI - Effect of specific membrane perturbations on alpha 1-adrenergic and muscarinic cholinergic signal transduction in rat parotid cell aggregates. AB - Alpha 1-adrenergic and muscarinic-cholinergic stimulated IP3 production and calcium mobilization are inhibited by treatment of parotid cell aggregates with methanol, hydrogen peroxide and saponin. Only methanol exerts an effect on binding to receptors. In most cases a close correspondence exists between inhibition of alpha 1-adrenergic and muscarini-cholinergic responses as well as inhibition of IP3 production and calcium mobilization. G-protein dependent signal transduction, therefore appears to be quite sensitive to plasma membrane perturbation and membrane active agents may provide useful tools for elucidation of transduction mechanisms and their regulation. PMID- 7997060 TI - Disturbances of the neuronal calcium homeostasis in the aging nervous system. AB - Maintenance of the cellular calcium homeostasis plays an important role for neuronal cell function and interneuronal cell to cell communication. Therefore, alterations of the neuronal Ca2+ homeostasis may play a crucial role for brain aging in general and for age-related deficits in cognitive functions particularly. Numerous studies indicate various disturbances of the Ca2+ homeostasis on different levels like Ca2+ channel properties, 45Ca2+ uptake, or Ca2+ binding proteins. Investigations on alterations of the free intracellular calcium concentration ([Ca2+]i) in presynaptic synaptosomal preparations led to inconsistent results reporting increased or unchanged [Ca2+]i in aged animals. Postsynaptic alterations of [Ca2+]i have been investigated mainly indirectly by electrophysiological methods and revealed prolonged Ca(2+)-dependent afterhyperpolarization or prolonged Ca2+ spike duration. By using acutely dissociated mouse brain cells it was possible for the first time to evaluate age dependent alterations of postsynaptic [Ca2+]i directly. In neurons of aged mice basal [Ca2+]i was reduced and depolarization-induced rise in [Ca2+]i was also reduced, probably as a result of increased activation of Ca(2+)-dependent mechanisms terminating Ca(2+)-influx. Depolarization-induced, Ca(2+)-mediated inositolphosphate accumulation was also increased in aged animals. This leads to the conclusion that Ca(2+)-dependent intracellular processes become more sensitive during aging. Investigations about the effect of beta-amyloid on the Ca2+ homeostasis in the same system revealed a small but consistent destabilizating effect of this peptide on K(+)-induced rise in [Ca2+]i which may result in chronically increased neuronal vulnerability. Together with increased Ca2+ sensitivity during aging this might be one of the reasons for the increasing prevalence of Alzheimer's disease (AD) with aging. PMID- 7997061 TI - Alterations of intracellular calcium regulation during aging and Alzheimer's disease in nonneuronal cells. AB - Because of its function as an intracellular messenger in many cells, calcium plays an important role in signal transduction. Changes in intracellular free calcium concentration occur in central neurons during aging and Alzheimer's disease (AD). It is possible that similar changes in peripheral cells could mirror or, at least parallel, similar abnormalities in the brain. Assuming that manifestations of the aging process and AD are also present outside the central nervous system, nonneuronal tissues like lymphocytes could be used to search directly for abnormalities in cellular calcium regulation in man. Consistent with observations of reduced depolarization-induced Ca2+ rises in dissociated neurons of aged mice, corresponding age-related changes of reduced mitogen-induced Ca2+ responses were observed both in mouse lymphocytes and, more importantly, in circulating human lymphocytes. With respect to AD, Ca2+ responses after stimulation were unaltered (compared to normal controls). In addition, freshly prepared human lymphocytes showed elevated mitogen-induced Ca2+ responses after exposure to beta-amyloid, the main component of senile plaques in AD. These findings again parallel our observations that this peptide amplifies the K(+) induced Ca2+ rise in acutely dissociated mouse brain cells. Thus, the lymphocyte seems to be a valuable model to study the effects of beta-amyloid in man. In a preliminary study with AD-patients, sensitivity of the lymphocytes to beta amyloid's effects on Ca2+ rise was reduced, an observation which was entirely unexpected. Nevertheless, such studies indicate lymphocytes may represent a promising candidate for a peripheral marker of AD and can contribute to the understanding of the disease process. PMID- 7997062 TI - Age-related changes in transcriptional and posttranscriptional regulation of the dopaminergic system. AB - Loss of striatal dopamine receptors is a major cause of decreased motor control and a robust biomarker of aging. Mechanisms of receptor loss include both neuronal death and decreased expression of receptor genes at the transcriptional and translational levels. PMID- 7997063 TI - Rodent models of memory dysfunction in Alzheimer's disease and normal aging: moving beyond the cholinergic hypothesis. AB - The Stone maze paradigm has been developed for use as a rat model of memory impairment observed in normal aging and in Alzheimer's disease. Results from several studies have demonstrated the involvement of both cholinergic and glutamatergic systems in acquisition performance in this complex maze task. Although results of clinical studies on the cognitive enhancing abilities of cholinomimetics for treatment of memory impairment in Alzheimer's disease have been inconsistent, new classes of cholinesterase inhibitors offer greater potential for therapeutic efficacy. The physostigimine derivative, phenserine, appears to have marked efficacy for improving learning performance of aged rats or of young rats treated with scopolamine in the Stone maze. Declines in markers of glutamatergic neurotransmission in Alzheimer's disease and in normal aging suggest that pharmacological manipulation of this system might also prove beneficial for cognitive enhancement. Treatment with glycine and/or polyamine agonists is suggested as a strategy for activating the N-methyl-D-aspartate (NMDA) subtype of glutamate receptor. In addition, the use of combined pharmacological activation of cholinergic and glutamatergic systems is suggested. Manipulation of signal transduction events should also be considered as a strategy for cognitive enhancement. The influx of Ca2+ through the channel formed by the NMDA receptor stimulates the production of the oxyradical, nitric oxide (NO*), via the action of nitric oxide synthase (NOS). Compounds that inhibit NOS activity impair acquisition in the Stone maze, suggesting an involvement of NO*. Thus, strategies for inducing NO* production to enhance cognitive performance may be beneficial. Because of the potential neurotoxicity for NO*, this strategy is not straightforward. Although many new directions beyond the cholinergic hypothesis can be suggested, each has its potential benefits which must be weighed against its risks. Nonetheless, an important unifying area for neurobiological research examining mechanisms of normal brain aging and of age related neuropathology, as observed in Alzheimer's disease, might emerge from the identification of NO* as a simple molecule serving vital physiological functions but representing potential for neurotoxicity. PMID- 7997064 TI - Cognition in humans and the borderline to dementia. AB - From a psychometric point of view, cognitive performance in humans has to be examined as a multidimensional quantitative construct. Models of memory and intelligence may serve to describe the complex interactions of cognitive functioning. Based on memory research and reliable psychometric methods a three dimensional model including "Primary Memory", "Secondary Memory" and a "Speed factor" is proposed. Using models of performance factors. "Cognitive Speed" is demonstrated as a marker variable of "Fluid Intelligence". It is shown, that "Cognitive Speed" is clearly age-associated and constitutes a key function for other cognitive domains and for activities-of-daily-living. Furthermore "Cognitive Speed" is a crucial cognitive domain to separate normal from pathological aging. As an example to assess "Cognitive Speed", the Zahlen Verbindungs-Test G (1), a modified trail-making test, is discussed to diagnose beginning and ongoing dementias. PMID- 7997065 TI - Interaction between psychological and pharmacological treatment in cognitive impairment. AB - In contrast to other kinds of psychotropic drugs, nootropics or cognition enhancing drugs may be indicated, not for the direct treatment of the pathology itself, but for improving or restoring the remaining brain functions. Brain functions are normally trained during various kinds of non-medical therapy, such as physiotherapy, speech therapy, occupational therapy, memory training etc... In research little attention has been paid to the combination of both kinds of therapeutic approaches, probably because of the important methodological difficulties. This combination however, offers various interesting perspectives: L. ISRAEL examined in two placebo-controlled studies the effects of either 160 mg/d of ginkgo biloba extractum (GBE) or piracetam 2.4 or 4.8 g/d, combined with a memory training program, in nondemented patients complaining of memory problems. The results of both studies suggest that nootropic drug treatment and memory training have each an effect on different cognitive functions and, hence, are complementary. Some functions, like attention/perception in the GBE study and learning in the piracetam study, seem to benefit from both treatments, suggesting a mutually potentiating effect of drug treatment and training. This potentiation is very clear in the treatment of dyslexic children: in a placebo-controlled study piracetam 3.3 g/d, in combination with normal school teaching and more specific logopedic therapy, allowed a normal progression during the full school year in reading accuracy and reading comprehension, while the placebo treated children getting a similar training progressed only with 50%. Recently promising results were obtained in the treatment of dysphasic patients with a combination of speech therapy and piracetam 4.8 g/d, especially when given during the first months after the stroke, or otherwise in combination with an intensive speech training. In both double-blind studies the piracetam treated group improved about 60% more than the group who only got speech therapy and placebo. All these data may be explained by the restorative or enhancing influence of nootropic drugs on neurotransmitter systems closely related to learning and memory functions. E.g. piracetam restores the availability and function of muscarinic and NMDA receptors in aging animals, most probably through a modulation of the psychico-chemical properties of the neuronal membrane such as the membrane fluidity. PMID- 7997066 TI - Glutamatergic drugs in Parkinson's disease. AB - Recent findings in monkeys indicate that excitatory amino acids such as glutamate are involved in the pathophysiological cascade of MPTP (1-methyl-4-phenyl-1,2,3,6 tetrahydropyridine)- induced neuronal cell death. The neuroprotective effects of competitive and non-competitive NMDA (N-methyl-D-aspartate) antagonists against MPTP toxicity support the hypothesis that NMDA receptor-mediated events are involved in the neurotoxicity of MPTP. These results suggest that the clinical trial of NMDA antagonists in patients with Parkinson's disease should be performed. Further evidence obtained in animal models of Parkinson's disease indicates that both competitive NMDA antagonists and AMPA (alpha-amino-3-hydroxy 5-methyl-4-isoxazolepropionate) antagonists show symptomatic anti-parkinsonian activity in combination with L-DOPA. Glutamate antagonists may therefore retard the progression and improve the symptomatology of Parkinson's disease. The 1 amino-adamantanes amantadine and memantine have recently been shown to be non competitive NMDA antagonists and are widely used in Europe as anti-parkinsonian agents. Both compounds are likely to cause pharmacotoxic psychosis as an unwanted side-effect. Clinical trials are needed to test the efficacy of the 1-amino adamantanes with respect to the progression of Parkinson's disease. PMID- 7997067 TI - Neural transplantation, trophic factors and Parkinson's disease. AB - Part 1 of this update on new restorative therapeutic strategies against Parkinsons's disease focuses on transplantation of dopamine-secreting tissue. Special emphasis is put on clinical trials with fetal mesencephalic cells. Problems and potential alternative approaches are discussed. Part 2 emphasizes progress in the related field of neurotrophic factors for dopaminergic midbrain neurons. PMID- 7997068 TI - Role of protein oxidation in aging and in age-associated neurodegenerative diseases. AB - Aging and age-associated neurodegenerative diseases have been proposed to be the result of changes in a in anti-oxidant status and in the production of reactive oxygen species. Studies in humans have demonstrated a significant increase in oxidized protein from brains of neurological normals and from individuals with different neurological diseases (Alzheimer's, Parkinson's and Huntington's Disease). Preclinical models of these conditions and of cerebral ischemia demonstrate the primary role of protein oxidation in the initial steps of these neurodegenerative diseases. Aging is a risk factor in the development of these diseases and is also associated with a decrease in the anti-oxidant defense systems of the brain. It is proposed that free radicals play a primary role in the initiation of those biochemical events that ultimately lead to the death of the neuron. PMID- 7997069 TI - Neuronal protective effects of calcium antagonists in cerebral ischemia. AB - We investigated the effects of calcium antagonists against ischemic injury in vivo and against excitotoxic damage in vitro. In vivo nimodipine protected significantly the CA1 hippocampal neurons from neurodegeneration after transient global ischemia in rats without changing the local cerebral blood flow. Furnidipine reduced the area of ischemia after permanent MCA-occlusion in mice. The results in vitro using the Ca(2+)-sensitive dye fura-2 showed that nimodipine reduced in a dose-dependent manner the elevation of [Ca2+]i in hippocampal neurons induced by K(+)-stimulation. The present in vitro and in vivo data show that calcium antagonists are potent agents in protecting neurons against the deleterious consequences of an excitotoxic or ischemic insult. PMID- 7997070 TI - Excitatory amino acid receptor antagonists: a novel treatment for ischemic cerebrovascular diseases. PMID- 7997071 TI - Gangliosides--a new therapeutic agent against stroke and Alzheimer's disease. AB - Gangliosides are glycosphingolipids localized to the outer leaflet of the plasma membrane of vertebrate cells. The highest ganglioside concentration of any organ is found in the mammalian brain, where the gangliosides are enriched in the neuronal membrane, particularly in the synapses. There are four major brain gangliosides with the same neutral tetrasaccharide core to which one to three sialic acids are linked--the simplest being the GM1-ganglioside. These gangliosides have been shown to have neuritogenic and neuronotrophic activity and to facilitate repair of neuronal tissue after mechanical, biochemical or toxic injuries. Mixtures of native bovine brain gangliosides were adopted for pharmacological use in the treatment of peripheral nerve damage, and GM1 ganglioside has been applied for the treatment of CNS injuries and diseases. Beneficial effects of GM1 have been documented in the treatment of stroke and spinal cord injuries, particularly when the treatment has been initiated within a few hours of the acute event. Continuous intraventricular infusion of GM1 has recently been shown to have a significant beneficial effect in Alzheimer disease of early onset (AD Type I). PMID- 7997072 TI - Muscarinic receptors and novel strategies for the treatment of age-related brain disorders. AB - The muscarinic class of acetylcholine receptors is widely distributed throughout the body and mediates numerous vital functions in both the brain and autonomic nervous system. Within the brain, muscarinic receptors play an important role in learning, memory and the control of posture. There is a decrease in the synthesizing enzyme for acetylcholine in Alzheimer's disease, and damage to the ascending cholinergic system is thought to be an important determinant of the loss of memory and other functional deficits of this disease. Five subtypes of the muscarinic receptor (m1-m5) have been identified, and these receptors have a differential distribution throughout the body. The differential distribution of subtypes of the muscarinic receptor in the body suggests that centrally acting m1 and m4 muscarinic agonists might be efficacious in the treatment of age-related memory disorders, without causing peripheral side effects. In addition to the primary ligand binding site, muscarinic receptors also possess a secondary allosteric site that appears to be the target for some novel cardioselective muscarinic antagonists including the neuromuscular blocking agent gallamine. The existence of a secondary allosteric site on the muscarinic receptor suggests that it might be possible to develop novel allosteric muscarinic agonists that potentiate the effects of endogenous acetylcholine much in the same way that benzodiazepines potentiate GABA. Although no such allosteric muscarinic agonists have been identified to date, they could be very efficacious in the treatment of Alzheimer's disease. PMID- 7997073 TI - Glutamatergic treatment strategies for age-related memory disorders. AB - Age-related changes of N-methyl-D-aspartate (NMDA) receptors have been found in cortical areas and in the hippocampus of many species. On the basis of a variety of experimental observations it has been suggested that the decrease of NMDA receptor density might be one of the causative factors of the cognitive decline with aging. Based on these findings several strategies have been developed to improve cognition by compensating the NMDA receptor deficits in aging. The most promising approaches are the indirect activation of glutamatergic neurotransmission by agonists of the glycine site or the restoration of the age related deficit of receptor density by several nootropics. PMID- 7997074 TI - Age-related memory decline and longevity under treatment with selegiline. AB - The MAO-B inhibitor selegiline is used in the treatment of Parkinson's disease. Further, beneficial effects in Alzheimer's disease have also been described as well as neuroprotective effects, increased longevity and an attenuation of age related cognitive decline in experiments using rats. Our studies in mice and Syrian hamsters aim at the question whether the effects of selegiline reported in the rat can be generalized to other species. Aged female NMRI-mice (23 mo.) treated with selegiline (0.25 mg/kg, i.p., 3 times a week for 2-3 weeks) showed no treatment effect in the Morris water maze and in passive avoidance learning after 2 and 3 weeks of treatment. However, Syrian hamsters chronically treated with selegiline (0.05 mg/kg/day in the food, starting at 12 months old) showed a 3 month delay in the age-related decline of spontaneous alteration behavior, a measure of longer-term memory, compared to untreated controls. Since treated hamsters also show increased longevity (study still in progress) the data suggest a protective effect of a chronic treatment with selegiline against age-related cognitive and physical decline. PMID- 7997075 TI - Neurotrophic factors in memory disorders. AB - Neurotrophic factors are target-derived proteins capable of affecting survival, target innervation, and/or function of neuronal cell populations. These factors are structurally and functionally related to the classical neurotrophic molecule nerve growth factor (NGF) and resemble a genetic family called neurotrophins. Besides NGF and brain-derived neurotrophic factor (BDNF), there is little knowledge whether these neurotrophins play a pathophysiological role in dementing brain disease(s). BDNF-mRNA levels are reported to be decreased in the hippocampus of individuals with Alzheimer's disease (AD). Decreased NGF production does not seem to play a causal role both in age-related cognitive impairment and AD which is usually associated with neurodegenerative processes in the cholinergic basal forebrain system. However, there are several experimental indications that NGF might be of importance for the stimulation of compensatory changes and repair mechanisms; given in pharmacological dose, NGF might be of therapeutical benefit, as reported in a preliminary clinical case study. Thus, the availability of sufficient quantities of recombinant human neurotrophins should allow comprehensive research programs in future. PMID- 7997076 TI - In search of the mechanism of action of the nootropics: new insights and potential clinical implications. AB - The positive action of nootropics on the memory has up to now primarily been discussed in the context of effects on energy metabolism and cholinergic or glutaminergic neurotransmission. Recent findings have shown that the memory enhancing effect is steroid-sensitive. Since corticosteroids are potent modulators of gene transcription, it appears possible that the nootropics may exert a modulatory action on protein synthesis. This assumption is supported on the one hand by the fact that the nootropics improve the memory even if they are administered several hours after the learning trial, and on the other hand by the observation that their memory-enhancing effect does not become detectable until 16-24 hours after the treatment and learning trial. Provided the memory-enhancing effect in animal experiments and the therapeutic effect in patients come about by way of the same mode of action, the fact that high levels of corticosteroids suppress the effects of the nootropics could also have clinical implications: in the light of the observation that the majority of Alzheimer patients have elevated steroid levels it could explain why there is always only a small proportion of patients in clinical trials that respond to treatment with nootropics. PMID- 7997077 TI - Towards a pharmacological approach of Alzheimer's disease based on the molecular biology of the amyloid precursor protein (APP). AB - After heart disease, cancer and stroke, Alzheimer's disease (AD) is the fourth major cause of death in the developed countries. Due to demographic changes, this situation will further worsen in the future. With the use of molecular biology techniques, important progress has recently been made in the understanding of the molecular changes leading to some forms of this disabling illness. The first step was the partial sequencing of the amyloid protein accumulating in the senile plaques and vascular deposits characteristic of AD. This allowed the cloning of a cDNA coding for a long amyloid precursor protein (APP). During the last few years, independent reports have described the presence of several reproducible point mutations in specific codons of APP in early onset familial Alzheimer patients. These mutations are responsible for an abnormal processing of APP, leading to the formation of pathological beta/A4 amyloid deposits. beta/A4 has been shown to possess neurotrophic properties in embryonic neurones and to be a potent neurotoxic agent in differentiated hippocampal neurones. More recently, modifications of intracellular calcium, activation of kinases, free radical generation and anomalies in potassium channels have been described as possible mechanisms of beta/A4 toxicity. Some forms of Apo-E lipoprotein may be an additional risk factor. Hence, it now seems possible to elaborate a coherent theory to explain the cascade of events leading to the development of AD. Genetically induced point mutations or environmental factors may produce a modification of the APP metabolism and processing. As a consequence, abnormal deposits of beta/A4 are formed. They may exert direct or indirect neurotoxic actions. A degeneration of cholinergic, catecholaminergic and other neurones follows, leading to the well known cognitive and behavioural changes of AD. PMID- 7997078 TI - Memory disorders: novel treatments, clinical perspective. AB - The aging of the society is accompanied by a strong pressure to develop drugs to treat age-related memory disorders. This paper examines the discrepancy between the results of preclinical tests, which have identified a large number of putative cognition enhancers, and the limited clinical efficacy of most of them. The predictivity of the preclinical tests is discussed, and the criteria for evaluating the therapeutic efficacy of the cognition enhancers are examined. An analysis is made of the novel treatments presently available or under investigation. In light of the results of the trials with tacrine a warning is given not to expect striking clinical improvements by only attempting to restore signal transmission, disrupted by aging and dementia, without modifying the underlying morphological alterations. PMID- 7997079 TI - Flucloxacillin-associated hepatic injury. AB - Eleven cases of hepatic injury attributed to the intake of flucloxacillin were reported to the Netherlands Center for Monitoring of Adverse Reactions to Drugs between 1982 and 1992. They concerned four men and seven women, with a mean age of 57 years, treated for 2-28 days with an oral dose varying from 1500-4000 mg per day. Symptoms mostly appeared 10 to 30 days after starting treatment with flucloxacillin. Biochemically, the pattern was compatible with cholestatic hepatitis in seven cases, with a mixed cholestatic-hepatocellular type of injury in one case, a hepatocellular pattern in two cases, and mild liver enzyme elevations in one patient. Two patients died, one due to fatal bleeding from the liver after biopsy, and the second patient to a combination of hepatic and cardiac failure. The other patients recovered, on average 72 days after peaking of serum aminotransferase values. Histology in seven cases showed cholestatic hepatitis in five, with cholangitis or cholangiolitis in four of these patients. In the other two patients, there was centrilobular cholestasis with extensive bridging fibrosis and portal-central bridging necrosis, respectively. PMID- 7997080 TI - Endotoxin-induced defenestration of the hepatic sinusoidal endothelium: a factor in the pathogenesis of cirrhosis? AB - Defenestration and capillarisation of the hepatic sinusoidal endothelium occurs early in the pathogenesis of cirrhosis, both in patients suffering from alcohol abuse and in animal models. It is possible also that alcohol abuse promotes the absorption of bacterial endotoxins from the gastrointestinal tract. In this study we have investigated the effects of a single intravenous injection of endotoxin on the hepatic sinusoidal endothelium of rats. Seven days after the dose of endotoxin, the porosity of the sinusoidal endothelium was reduced to 40% of that of controls, due to a decrease in both diameter and number of fenestrae. The livers examined 14 days after dosing exhibited normal porosity. We postulate that bacterial endotoxins play a role in the pathogenesis of cirrhosis by modulating the fenestrated sinusoidal endothelium (liver sieve). PMID- 7997081 TI - Oxidative stress in hepatocytes and stimulatory state of Kupffer cells after reperfusion differ between warm and cold ischemia in rats. AB - Rat liver was kept at 4 degrees C or 37 degrees C in MEM, and reperfused through a closed circulation from the hepatic vein to the portal vein at 37 degrees C with the same solution. Although purine nucleoside phosphorylase and ALT activities were increased in the perfusate, depending on the duration of ischemia at both 4 degrees C and 37 degrees C, the ratio of the latter to the former was significantly higher after 37 degrees C-ischemia than after 4 degrees C-ischemia. The stimulation stage of Kupffer cells evaluated in situ by formazan deposition after liver perfusion with nitro blue tetrazolium and phorbol myristate acetate was elevated after 4 degrees C-ischemia longer than 1 h, but not after 37 degrees C-ischemia. In contrast, the degree of oxidative stress in hepatocytes assessed by formazan deposition after liver perfusion with nitro blue tetrazolium alone was greater after 37 degrees C-ischemia than after 4 degrees C-ischemia. These results suggest that oxidative stress in hepatocytes and the stimulatory state of Kupffer cells after ischemia-reperfusion may differ between 4 degrees C-ischemia and 37 degrees C-ischemia, probably leading to different development of liver damage. PMID- 7997082 TI - Inapparent "wild-type" and "e-minus variant" HBV infection in patients with HCV related chronic hepatitis. AB - We analysed DNA extracted from liver biopsy specimens and serum samples from 42 HCV-RNA-positive/HBsAg-negative subjects with chronic hepatitis. Twenty-eight of them were anti-HBs/anti-HBc-positive (group A), while 14 were negative for all HBV markers (group B). HBV sequences were found in hepatic DNA of 12 cases (11 of group A, one of group B), but in the serum of only two cases of group A. Sequencing analysis of pre-core region of HBV-DNA showed the presence of wild type HBV in three cases, HBeAg-defective HBV in three cases, and the coexistence of both viral populations in six cases. These results indicate that HBV and HCV infection may coexist in HBsAg-negative chronic hepatitis, particularly in anti HBs/anti-HBc-positive patients. However, HBV replication appears suppressed in these cases, and this state of latency may involve both wild and HBeAg-defective HBV types. PMID- 7997083 TI - Immunological functions of mouse liver resident high density lymphocytes. AB - Liver-derived high density lymphocytes (Matsunaga cells) have been detected as members of resident T cells in the mouse liver. In this study, we assessed the immunological functions of liver-derived high density lymphocytes of BALB/c mice in comparison with those derived from spleen and peripheral blood. Liver-derived high density lymphocytes proliferated in response to the syngeneic and allogeneic mixed lymphocyte reaction, as well as those derived from spleen and peripheral blood. The allo-activated cytotoxic T lymphocyte activity of liver-derived high density lymphocytes against PHA-blasts of C57BL/6 mice was lower than that of spleen- and peripheral blood-derived lymphocytes. The suppressor activity of syngeneic- or allo-activated high density lymphocytes of the liver, spleen, and the peripheral blood was assessed by measuring their suppressive effect on the proliferation or on the generation of allo-specific cytotoxic activity in allogeneic mixed lymphocyte reaction. The suppression was concentration-dependent and strongest in liver-derived lymphocytes. PMID- 7997084 TI - Pathology of livers infected with "silent" hepatitis B virus mutant. AB - We have discovered that non-A, non-B, non-C, non-D, non-E (so-called type F) acute and chronic hepatitis is caused by a hepatitis B virus (HBV) variant with mutations in the X open reading frame. This silent HBV mutant does not induce immunoserological markers. In the present investigation we attempted to elucidate the putative mechanism of hepatocellular necrosis and expression patterns of hepatitis B surface antigen (HBsAg) and core antigen (HBcAg) in biopsied liver tissue. The subjects consisted of 14 patients with acute hepatitis, 11 with chronic hepatitis and eight with liver cirrhosis, all of whom had been previously diagnosed as having so-called hepatitis F. Nine of the 14, 10 of the 11 and all eight, respectively, of the above patients exhibited significant positive immunostaining for HBsAg within their hepatocellular cytoplasm, diffusely or focally. HBcAg stained in a few hepatocellular nuclei in 24.2% of the patients. Histological features were characterized by necroinflammation, indicating immune mediated hepatocellular necrosis. Despite the serological-marker negativity, the results of immunostaining for HBsAg and HBcAg support replication and expression of HBV DNA, though weak. PMID- 7997085 TI - Serum markers of hepatic fibrogenesis in chronic hepatitis type C treated with alfa-2A interferon. AB - Hepatic fibrogenesis is a dynamic process which characterizes the course of chronic hepatitis. It has stimulated interest in the possible effect of interferon therapy on liver fibrosis. We have evaluated a panel of serum markers of fibrogenesis, namely N-terminal procollagen III peptide (PII-INP), C-terminal procollagen I peptide (PICP), laminin and hyaluronate in 35 patients with chronic hepatitis type C, before, during and after interferon treatment. Before treatment, PIIINP was elevated in 8.5%, 44% and 71% of patients with chronic persistent hepatitis, chronic active hepatitis and cirrhosis, respectively, while the corresponding figures for PICP were 0%, 50% and 46%, and for laminin 16.5%, 70% and 71%; hyaluronate was elevated in only five out of seven patients with cirrhosis. Patients with high PIIINP levels at presentation and a persistent response to treatment showed persistent normalization of this parameter, which was not observed in non-responders. In contrast, the other markers showed no significant correlation with interferon response. These results indicate that PIIINP correlates with interferon response in chronic hepatitis type C. PMID- 7997086 TI - An electron microscopic study of apoptosis induced by cycloheximide in rat liver. AB - A histological and ultrastructural study, coupled with transmission and scanning electron microscopy of the early changes in the liver following a single administration of cycloheximide (CHX), was carried out in male Wistar rats. At the histological level, apoptosis was already present in the liver 2 h after treatment. By scanning electron microscopy, the following sequential changes were observed: brightness and progressive detachment of hepatocytes from neighbouring cells, formation of surface infolds with multiple blebs and, finally, release of several membrane-bounded apoptotic bodies (ABs) in the extracellular space and into the sinusoidal lumen. Three hours after CHX administration, the apoptotic cycle was completed, as shown by the presence of phagocytosed ABs inside the cytoplasm of intact liver cells. Light microscopic examination of the liver 6 h after CHX administration showed ABs mainly located in the cytoplasm of intact hepatocytes and inside activated Kupffer cells. By transmission electron microscopy, it was possible to demonstrate that cells undergoing apoptosis were hepatocytes. At 24 h, the livers of treated animals appeared normal, with no evidence of apoptosis. PMID- 7997088 TI - Visualization of subtle contrast-related intensity changes using temporal correlation. AB - Contrast-enhanced magnetic resonance imaging (MRI) is a promising method for investigating the breakdown of the blood-retinal barrier (BRB). However, subtle intensity changes due to low concentrations of contrast agent can be difficult to detect without observer bias. In this study, we developed a temporal correlation method for detecting these subtle signal intensity changes. The method was evaluated in eyes with chemically induced retinal lesions of known size. A time series of MRI data were collected following i.v. administration of different doses of gadolinium-diethylaminetriaminepentaacetic acid (0.05, 0.1, 0.5 mmol/kg). These time course images were analyzed by temporal correlation to a reference enhancement curve. The reference curve was generated based on a validated theoretical enhancement curve. The temporal correlation method detected signal intensity changes in cases where the changes were too subtle to be visible on a postinjection image or a subtraction image (obtained by subtracting the precontrast image from the final image in the time course set). In addition, assessment of leakage was performed by viewing each image in the set with an eight gray-level palette. Areas of leakage identified in this manner corresponded to those identified by temporal correlation, a finding which supports the validity of the temporal correlation method. These results suggest that temporal correlation may be a time-efficient way to screen large numbers of image data sets using an objective, user-independent criterion. PMID- 7997089 TI - MR imaging assisted temperature calculations during cryosurgery. AB - MRI has the potential of becoming an important imaging modality for monitoring the extent of the frozen region during cryosurgery. However, while the temperature history inside the frozen region is of utmost importance in determining the likely outcome of a cryosurgical procedure, it cannot be accessed directly through MRI because of the extremely low signal produced by the frozen region. We have developed a new MRI-assisted numerical technique that can calculate and display the temperature distribution in the frozen region on a standard MR image. The technique combines MR imaging data with a finite difference formulation of the energy equation. Here, the technique is described and experimental results that verify the technique are shown. PMID- 7997087 TI - Sources of heterogeneous contrast enhancement in the gastrointestinal tract. AB - Water soluble gadolinium chelates demonstrate heterogeneous enhancement of the gastrointestinal tract (GI) when administered orally. To investigate the causes, ProHance (2.0 mM) was administered orally to rats. There was a dramatic enhancement of rat GI lumen signal intensity in T1-weighted MR images which provided increased contrast relative to the adjacent abdominal tissues. Heterogeneity of MRI signal enhancement along the rat GI tract was investigated by sampling rat GI fluid at various times post-ingestion and at different locations along the GI tract. The corresponding T1 and T2 relaxation times, Gd concentrations, and viscosities of each GI fluid sample revealed that changes in each of these parameters contribute to the observed heterogeneity of MRI signal enhancement. PMID- 7997090 TI - Single-shot-double-echo EPI. AB - Echo planar imaging (EPI) was extended for the acquisition of both, the spin-echo (SE) and the stimulated echo in a stimulated echo sequence after one excitation from thermal equilibrium. The two independent EPI images reflect different states of the transverse magnetization excited and measured almost simultaneously. This single-shot-double-echo EPI approach offers a variety of useful applications such as varying image contrast, obtaining flow or diffusion information, improving image resolution or circumventing T*2 requirements in single shot EPI. Benefits and limits of this technique are discussed. PMID- 7997091 TI - Evaluation of a rabbit model for osteomyelitis by high field, high resolution imaging using the chemical-shift-specific-slice-selection technique. AB - The rabbit model of osteomyelitis introduced by C.W. Norden, based on injection of an infecting solution (Staphylococcus aureus, sodium morrhuate) into the tibia, was studied at 4.7 Tesla with a time-efficient chemical shift selective imaging technique, Chemical Shift Specific Slice Selection (C4S). The evolution of the disease over several weeks was followed on water-selective, fat-selective, and sum images obtained simultaneously with this imaging sequence. Experiments were performed either on different groups of rabbits at different times after infection with subsequent sacrifice of the animal and microbiological analysis of the infected tibia or on the same group of animals imaged several times after infection. Associated analysis of the water and fat selective images revealed marrow modifications very early (Day 5 after inoculation) demonstrating the high sensitivity of the employed imaging technique. Later on, bone modifications were best identified on the sum images. Additional experiments performed on animals injected with a noninfecting solution containing only sodium morrhuate showed however that the sclerosing agent alone can yield images similar to those produced by infection at early stages after inoculation. Therefore, the Norden model would not be suitable for monitoring quantitatively outcome of therapy by magnetic resonance imaging. It is however well adapted for the evaluation and optimization of MRI techniques or protocols intended to detect early changes of bone marrow produced by septic or aseptic infarct. PMID- 7997092 TI - Fast imaging in liquids and solids with the Back-projection Low Angle ShoT (BLAST) technique. AB - A simple fast imaging scheme is proposed, which is applicable to solid- and liquid-like materials. It is based on low angle pulse excitation in combination with back-projection reconstruction and proper data handling and is called Back projection Low Angle ShoT (BLAST) technique. The sequence is applied to grape as a biological sample and to a jellibaby (2 kHz linewidth at half intensity) for demonstration of the applicability to solid objects. PMID- 7997093 TI - An MRI study of drying in granular beds of nonporous particles. AB - MRI is used to study the role of capillary and gravitational forces in controlling mass transport of water during isothermal drying of granular beds of nonporous particles. A new model is presented that shows how capillary and gravitational forces relate to Fickian diffusion driven by a chemical potential gradient. In granular beds, where capillary and gravitational forces dominate, the image profiles give direct information on the dependence of the degree of saturation on capillary suction pressure. The effects of changing particle size and surface tension on the profiles is investigated quantitatively, and it is shown that high capillary pressures create anomalies in the drying profiles. PMID- 7997094 TI - NMR-imaging of water content in the polymer matrix of silicon chips. AB - The distribution of water in the polymer matrix of a silicon microchip was studied by NMR imaging. The chip was saturated with water in a water steam atmosphere and then dried in five steps. After every change of the water content a three-dimensional (3D) NMR image was acquired. A 3D back-projection spin-echo sequence was used to avoid fast gradient switching during the sequence. The experiments show that water invades the chip mainly through the gap between the metallic parts and the polymer body. PMID- 7997095 TI - RF coil optimization: evaluation of B1 field homogeneity using field histograms and finite element calculations. AB - Two-dimensional (2D) finite element analysis has been used to solve the full set of Maxwell's equations for the 2D magnetic field of radiofrequency (RF) coils. The field histogram method has been applied to evaluate and optimize the magnetic field homogeneity of some commonly used RF coils: the saddle coil, the slotted tube resonator, the multiple elements coil and the birdcage resonator, as well as the radial plate coil. Each coil model represents a cross-section of an infinitely long cylinder. The optimum configuration of each of these five RF coils is suggested. It was found that field homogeneity is more strongly dependent on the coil's window angle than on any other parameter. Additionally, eddy currents in the coil's conductive elements distort the current and magnetic field distribution. The frequency dependence of this eddy current distortion is analyzed and discussed. PMID- 7997096 TI - MRI scanner variability studies using a semi-automated analysis system. AB - Due to the unique design of the Parallel Rod Test Object (PRoTO) and the associated semi-automated analysis program, it was necessary to test it extensively for precision and accuracy, and preliminarily for utility, before its distribution for wider use in MRI system quality control (QC). The test object and analysis program measured the desired quantities reproducibly and they accurately measured predicted changes from intentionally adjusted imaging system parameters, yielding sensitivity of the various test measures to deviation in the system operating parameters. From a single scan of the most recent revision of the test object, multiple quantitative quality control measures were obtained throughout the scanning volume on two MR imaging systems over periods of six and twelve months, respectively. From these and earlier trials, an initial indication was obtained of which performance measures are worth monitoring for QC. This experience suggests that signal-to-noise ratio (SNR) and distortion (including display scale) should be monitored but not necessarily the resolution. The latter was only found to alter at the same time or later than other parameters such as SNR had changed. Slice thickness was found to vary on some units and this measure was also used in normalizing the SNR by voxel volume. SNR, distortion, and resolution measurements using field-echo sequences were less stable than those using spin-echo sequences. Use of this QC program to test a wide variety of image quality measures allowed timely assessment of the long-term variability of the units tested. Long-term variability may become among the most important measures for comparison of system performance and maintenance.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7997097 TI - In vivo tissue characterization of human brain by chisquares parameter maps: multiparameter proton T2-relaxation analysis. AB - The heterogeneous proton MR relaxation decay process in human brain has been investigated by performing region-of-interest and pixel-by-pixel calculations on the multiecho MR images with different repetition times (TR) of human brains using a clinical 1.5-T whole-body superconducting MR scanner. Based on the monoexponential, biexponential, and continuous gaussian distribution relaxation models, first-order proton relaxation parameters (proton density, T1 and T2) and higher-order transverse proton relaxation parameters (T2-long, T2-short, T2-long fraction, T2-average, and T2-distribution width) were calculated. On the basis of an F test (p < .01), the statistical significance of the higher-order (biexponential and distribution) fits over the monoexponential fit was evaluated. Here, a significant improvement in the biexponential fit was found for some of the regions containing the ventricular cerebrospinal fluid (CSF) (T2-long = 2780 +/- 570 ms; T2-short = 159 +/- 42 ms; T2-long fraction = 0.51 +/- 0.08 ms) due to the partial volume effect but not for most of the white matter (WM). On the other hand, an improvement of fit to WM was obtained when distribution (T2-average = 80 +/- 8 ms; T2-distribution half-width = 21 +/- 4 ms) as opposed to monoexponential (T2 = 89 +/- 10 ms) fit was used. As internal controls, tubes of CuSO4 solution (T2 = 1293 +/- 128 ms) and agarose gel (T2 = 111 +/- 10 ms) which have similar T2 values as the CSF and WM of the brain, respectively, were attached to the human head and imaged concomitantly. No significance improvements in either the biexponential or distribution fits over the monoexponential fit were found for all the controls. In addition to the first-order and higher-order relaxation parameter maps, the monoexponential chisquares, as well as the chisquares ratio (chisquares of the monoexponential fit divided by that of the higher-order fit), maps were also generated. Unlike the higher-order T2-relaxation parameter maps, the chisquares parameter maps required no selection of any predetermined statistical confidence level. Therefore, these chisquares parameter maps provided a somewhat nonsubjective spatial profile of the heterogeneous transverse relaxation process in the brain. Our results led us to propose that the use of chisquares parameter maps, together with the first-and higher-order relaxation parameter maps, may further improve the in vivo tissue characterization capability of MRI in future clinical diagnosis and staging of intracranial diseases. PMID- 7997098 TI - MR image compression using a wavelet transform coding algorithm. AB - We present here a technique for MR image compression. It is based on a transform coding scheme using the wavelet transform and vector quantization. Experimental results show that the method offers high compression ratios with low degradation of the image quality. The technique is expected to be particularly useful wherever storing and transmitting large numbers of images is necessary. PMID- 7997099 TI - Imaging of phosphoenergetic state and intracellular pH in human calf muscles after exercise by 31P NMR spectroscopy. AB - Phosphoenergetic and pH images in human calf muscles before and after ischemic exercise were generated by 31P NMR chemical shift imaging (CSI) with a 1.5 T standard clinical MR machine using a home-built volume coil. Acquisition of data was repeated four times with 8 x 8 phase-encoding steps and 1 s repetition time. The total acquisition time was 4 min 16 s. After 3-dimensional (3D) Fourier transformation with zero-filling, 2-dimensional (2D) images with 32 x 32 matrices of phosphocreatine (PCr), inorganic phosphate (Pi), PCr/(PCr + Pi) and pH were constructed. These metabolic images were overlaid with concurrently observed 1H MRI to locate the areas showing metabolic response. After 3 min exercise consisting of repeated plantarflexion of the foot under ischemic conditions, decreases in phosphoenergetic levels and acidosis were the most severe in the peroneus muscles, moderate in the tibialis anterior muscle, and slight in the triceps muscle of the calf. Under maintained ischemic conditions, phosphoenergetic level further decreased, but the acidosis in each muscle did not progress further. Heterogeneous metabolic and pH changes throughout the entire calf muscle were clearly demonstrated in detail by these images. PMID- 7997101 TI - Detection of glomus tumor of the finger by dedicated MRI at 0.1 T. AB - Three glomus tumors of the fingers were detected using a dedicated hand and wrist low field (0.1 T) MR imager equipped with solenoidal coils allowing a FOV of 2 cm. Three-dimensional T1-, T*2-, or T2-weighted images were used (8 contiguous slices of 2 mm thickness). Glomus tumors had low or intermediate signal intensity (2 cases) or no signal (1 case) on T1-weighted images. On T*2- or T2-weighted images they had high signal intensity. MRI findings correlate well with surgery and biopsy. PMID- 7997100 TI - Correction of partial volume inaccuracies in quantitative phase contrast MR angiography. AB - The phase difference method of phase contrast MR angiography provides a means of measuring the average velocity in each voxel of an MR scan. When static tissue is present in a voxel containing flow, the measured velocity is not the average velocity of the flow alone, but is lower due to the partial volume effect of the static tissue. We present a preprocessing technique that removes the contribution of static tissue in each voxel prior to calculation of average velocity, resulting in more accurate velocity measurements and better lumen definition. Results of flow tube experiments are presented which confirm the improvement in measurement accuracy. PMID- 7997102 TI - Functional magnetic resonance imaging at 1.5 T: activation pattern in schizophrenic patients receiving neuroleptic medication. AB - Activation of the cerebral cortex during motor task performance can be visualised with functional MRI. A modified FLASH sequence (TR/TE/alpha 100/60/40 degrees, first order flow rephased, fat suppression, reduced bandwidth 28 Hz/pixel, 120 repetitions, three cycles of rest and finger movement for each hand) on a standard 1.5 T clinical imager was used to investigate 10 schizophrenic patients receiving clozapine and 10 healthy volunteers. All subjects were right-handed. Color-coded statistical parametric maps (SPM) based on the Student's t-test were calculated. A grid overlay was used for global and regional quantification. Activation strength was defined as the mean t-value of the respective region. All patients and volunteers showed a significant activation in the contralateral and ipsilateral sensorimotor cortex during motor task performance. The schizophrenic patients showed a significantly reduced global activation strength compared with healthy volunteers (p < .005). Selective evaluation of left-hand compared to right-hand movement demonstrated an increase in global activation strength in volunteers in contrast to a decrease in patients. Furthermore a reduced coactivation in the dominant left hemisphere was found in patients compared to volunteers during movement of the ipsilateral (left) hand. We conclude that alterations of the right and left hemispheric balance can be detected in schizophrenic patients using functional MRI at 1.5 T. These changes may indicate a disturbed interhemispheric interaction in schizophrenia. The reduction in cortical activation may result from several causes, however, taken together with previous studies and the underlying physiological effects, the most likely explanation is a combined effect of the disease and the neuroleptic medication. PMID- 7997103 TI - Short tau inversion recovery fast spin-echo (fast STIR) imaging of the spinal cord in multiple sclerosis. AB - The short tau inversion recovery fast spin-echo pulse sequence (fast STIR) combines the synergistic T1 and T2 contrast mechanism of conventional STIR with the reduced imaging time of fast spin-echo (FSE). We have compared fast STIR with T2-weighted FSE in evaluating the spinal cord lesions in 17 patients with multiple sclerosis and 12 healthy controls. Intrinsic lesions were seen only in patients. Twenty-five of the 58 lesions identified were more clearly demonstrated by fast STIR, 22 by FSE. Signal-to-noise and contrast-to-noise ratios were higher in all cases on FSE, suggesting other mechanisms, in particular choice of window settings and brightness of surrounding structures, must play a part in lesion conspicuousness. Fast STIR is a useful adjunct to FSE in the evaluation of multiple sclerosis in the spinal cord. PMID- 7997104 TI - Acute change of exercised muscle using magnetization transfer contrast MR imaging. AB - We evaluated the acute changes in exercised muscle using magnetization transfer contrast (MTC) MR imaging with a short repetition time sequence. Ten volunteers performed supine ankle dorsiflexion exercise. MTC gradient-recalled echo (GRE) images were obtained before and after exercise at 1.5 T. The effect of MTC was assessed by dividing the signal intensity on MTC GRE images by that on conventional GRE images (M(s)/M0). The signal intensity, M(s)/M0 and cross sectional area of exercised muscle were all greater at 1-2 min after exercise than immediately after exercise. We propose that this additional increase in these parameters after exercise was due to physiological reflow or hyperemia. Since the M(s)/M0 showed a good correlation with free water content in exercised muscle, this ratio may provide a quantitative variable for evaluating dynamic change of water-macromolecule interaction in skeletal muscle. PMID- 7997105 TI - Liver iron quantification: studies in aqueous iron solutions, iron overloaded rats, and patients with hereditary hemochromatosis. AB - For the noninvasive liver iron quantification by MRI in human iron overload diseases, fundamental proton relaxation mechanisms were studied in aqueous solutions with ferritin and other iron compounds, in experimentally iron overloaded rats, and in patients with iron overload diseases. MR-relaxation rates as a function of iron concentrations in the range of 0-7.5 mg Fe/g aqueous iron solutions, 0-5.4 mg Fe/g rat liver in vivo, and 0.16-4.9 mg Fe/g human liver in vivo were determined from multi- and sets of single-spin echo sequences (1.5 T imager). As predicted by theory, transverse relaxation rates (1/T2) in aqueous iron solutions, in liver tissue of rats, and in human liver tissue increased linearly with the iron concentration. A preliminary calibration for the liver iron quantification by MRI was performed from in vivo measurements of liver 1/T2 relaxation rates and liver iron quantification by atomic absorption spectroscopy in biopsies from 13 patients. With the single spin-echo method, precise in vivo liver iron quantification in humans also above 2.0 mg Fe/g liver tissue (T2 < 15 ms) should be accomplished on any imager with shortest spin-echo time available, at least TE < 20 ms. PMID- 7997106 TI - Abstract scoring for the annual SMR program: significance of reviewer score normalization. AB - Presently, the scores of three to four reviewers of each abstract are averaged and form a major component of the input for decisions made in choosing papers for oral and poster presentations, and in rejecting others. No normalization is made for differences in either mean or standard deviation between the reviewers of the same abstracts. In this paper, several techniques for normalizing the scores of reviewers are examined, and the consequences of applying such normalizations to several categories of the 1994 abstract submissions are examined. It was found that some alterations in the acceptance and assignments of papers as oral and posters resulted for one of the categories, and the normalized scores were used during the program assembly. It is recommended that future review procedures utilize reviewer normalization. PMID- 7997107 TI - Quantitation of lipid in biological tissue by chemical shift magnetic resonance imaging. AB - A method combining several previously used approaches is described for the rapid, accurate quantitation of the fat content of biological tissue based on chemical shift images (CSI) corrected for magnetic field inhomogeneity, and compensated for T1 and T2 effects. The gravimetrically determined lipid content of fatty tissues (pork fat, rabbit and human liver) that had been differentially depleted of lipid by chloroform extraction correlated well (r = 0.99) with the lipid image intensities of the respective tissues. This multi-point CSI method was used to quantitate lipid in fresh fatty human liver tissue (wet and dry) containing varying amounts of lipid. Plots of integrated lipid intensity versus tissue lipid content gave straight parallel lines for hydrated (r = 0.94) and dehydrated (r = 0.98) tissues, permitting determination of a proportionality constant for measuring absolute amounts of lipid present in a specific biological tissue. These results suggest the feasibility of using the method in vivo for absolute quantitation of lipid in tissues of agricultural (e.g. pork, beef) and medical (e.g. human liver) interest. PMID- 7997108 TI - Assessment of absolute metabolite concentrations in human tissue by 31P MRS in vivo. Part I: Cerebrum, cerebellum, cerebral gray and white matter. AB - Absolute metabolite concentrations were determined in four different brain regions using phosphorus magnetic resonance spectroscopy (31P MRS) on 10 healthy adult volunteers. Localized spectra were collected simultaneously from the cerebellum and the cerebrum and, later, from deep white matter and cortical gray matter by means of a two-volume ISIS pulse sequence and a Helmholtz-type RF-coli. Each brain spectrum was quantified with a calibration spectrum from a head-shaped simulation phantom. A time-domain fitting routine was used to process the fully relaxed data. Several metabolite concentrations (mmol/liter) differed significantly between the cerebrum and the cerebellum (PME = 3.2 +/- 0.3 and 4.0 +/- 0.6, PCr = 2.9 +/- 0.3 and 3.9 +/- 0.4, NTP = 2.9 +/- 0.2 and 2.6 +/- 0.2, respectively) and between cortical gray matter and deep white matter (PME = 3.1 +/- 0.4 and 4.3 +/- 0.8, PDE = 10.1 +/- 2.5 and 14.2 +/- 2.6, respectively). The concentration of free magnesium ion was found to be similar in all four brain regions (0.53 +/- 0.21 mmol/liter) but the intracellular pH was significantly higher in the cerebellum (7.04 +/- 0.03) than in the cerebrum (6.99 +/- 0.02). PMID- 7997109 TI - Assessment of absolute metabolite concentrations in human tissue by 31P MRS in vivo. Part II: Muscle, liver, kidney. AB - Absolute metabolite concentrations were assessed in the muscle, the liver, and the kidney of healthy human volunteers by 31P MRS. Fully relaxed in vivo spectra were acquired with a surface coil and were localized with an adiabatic ISIS pulse sequence. The spectra were quantified with a subsequent measurement of a calibration phantom and were processed iteratively in the time domain. The following mean metabolite concentrations (mmol/liter) were measured in the resting male calf muscle (n = 9), in the fasting liver (n = 12), and in the orthotopic kidney (n = 5): [PME] = 2.0 +/- 0.6, 3.8 +/- 0.7, and 2.6 +/- 0.9, [Pi] = 2.9 +/- 0.3, 1.8 +/- 0.3, and 1.6 +/- 0.4, [PDE] = 3.8 +/- 0.8, 9.7 +/- 1.5, and 4.9 +/- 1.1, [PCr] = 22.0 +/- 1.2, 0, and 0, [NTP] = 5.7 +/- 0.4, 2.9 +/ 0.4, and 2.0 +/- 0.3, respectively. Several interesting findings are to be emphasized: The concentrations of Pi, PCr, and NTP were 20% lower in the muscle of women than of men. In addition, the pHi was significantly lower in female muscle (6.99 +/- 0.03) than in male muscle (7.05 +/- 0.03). The pHi in the liver (7.12 +/- 0.09) and in the kidney (7.09 +/- 0.08) were higher than in the muscle of both genders. The free magnesium concentration (mmol/liter) was higher in the liver (1.40 +/- 0.64) than in the kidney (0.79 +/- 0.39) and in the muscle (0.52 +/- 0.10). PMID- 7997110 TI - Transition from Lorentzian to Gaussian line shape of magnetization transfer spectrum in bovine serum albumin solutions. AB - Magnetization transfer experiments using an off-resonance irradiation technique were performed on bovine serum albumin solutions by varying the irradiation frequency and the concentration. A transition of the magnetization transfer spectrum from Lorentzian to Gaussian line shape was observed around the critical concentration of 6.2 mmoles of protein to kg of solution. Observed magnetizations were well expressed by the rate equations of populations for spins below and above the transition, which yielded the magnetization transfer rates, the intrinsic relaxation rates of both protein and water protons, and the effective tumbling time and the rigid line width of the protein. The result showed that the estimates of the values for magnetization transfer rate do not change once the critical concentration is reached. PMID- 7997111 TI - A quantitative interpretation of IVIM measurements of vascular perfusion in the rat brain. AB - Pulsed gradient spin echo (PGSE) sequences have been used to measure the signal loss of 19F in perfluorinated hydrocarbon blood substitutes moving within the vasculature of the rat brain in the experimental conditions of the study. The signal loss is not characterized by a single apparent pseudodiffusion coefficient. A simple vascular network model based on self-similarity has been used to calculate the shape of the signal loss. Excellent agreement with the experiment has been obtained showing that the IVIM measurements are sensitive to flow over a wide range of vessel diameters and flow rates. This model of vascular structure may serve well for other MR measurements that are sensitive to perfusion. PMID- 7997112 TI - Localized MR 1H spectroscopy reveals alterations of susceptibility in bone marrow with hemosiderosis. AB - A noninvasive investigation of the structure of hemopoietic bone marrow is based on the determination of the magnetic field distribution within small volume elements in vertebral bodies by localized 1H MR spectroscopy. In patients with hematological diseases the status of the bone marrow was found to considerably influence the homogeneity of the magnetic field in trabecular bone in vivo. The line widths of the 1H signals were evaluated in follow-up studies during initial chemotherapy of eight patients with leukemia. Intraindividual comparison revealed significant broadening of the field distribution after a few weeks of cytotoxic treatment in five of the patients. Additionally, 19 patients after bone marrow transplantation showed significantly broader field distributions in the lipid signals than 13 matched healthy volunteers. These alterations of the microscopic field homogeneity were not caused by trabecular density effects. Iliac crest biopsies revealed high amounts of hemosiderin in the cases with broadened line widths. Ten of the 19 patients after bone marrow transplantation showed high amounts of hemosiderin and broad lines in the spectra. The content of hemosiderin of the other patients was not significantly increased. PMID- 7997113 TI - Magnetic resonance velocity imaging using a fast spiral phase contrast sequence. AB - Time-resolved velocity imaging using the magnetic resonance phase contrast technique can provide clinically important quantitative flow measurements in vivo but suffers from long scan times when based on conventional spin-warp sequences. This can be particularly problematic when imaging regions of the abdomen and thorax because of respiratory motion. We present a rapid phase contrast sequence based on an interleaved spiral k-space data acquisition that permits time resolved, three-direction velocity imaging within a breath-hold. Results of steady and pulsatile flow phantom experiments are presented, which indicate excellent agreement between our technique and through plane flow measurements made with an in-line ultrasound probe. Also shown are results of normal volunteer studies of the carotids, renal arteries, and heart. PMID- 7997114 TI - Quantitative MRI of spinal cord injury in a rat model. AB - Sequential in vivo MRI studies of experimental spinal cord injuries (SCI) were performed using a three-dimensional implementation of the FATE (Fast low-Angle spin echo sequence with short TE) sequence. MRI-observed pathology was quantified using a multispectral segmentation algorithm. Neurological analysis was performed on the same animals concurrently, in addition to end-point histology, for comparison with quantitative MRI results. These studies suggest that it is possible to use MRI to detect the onset of secondary injury in the spinal cord. The data also indicate that early detection of MRI-visible pathology may provide the necessary markers for predicting the long-term level of neurologic deficit. PMID- 7997115 TI - The design and test of a new volume coil for high field imaging. AB - A major problem in the development of high field (> 100 MHz) large volume (> 6000 cm3) MR coils is the interaction of the coil with the subject as well as the radiation loss to the environment. To reduce subject perturbation of the coil resonance modes, a volume coil that uses an array of freely rotating resonant elements radially mounted between two concentric cylinders was designed for operation at 170 MHz. Substantial electromagnetic energy is stored in the resonant elements outside the sample region without compromising the efficiency of the overall coil. This stored energy reduces the effect of the subject on the circuit and maintains a high Q, facilitating the tuning and matching of the coil. The unloaded Q of the coil is 680; when loaded with a head, it was 129. The ratio of 5.3 of the unloaded to loaded Q supports the notion that the efficiency of the coil was maintained in comparison with previous designs. The power requirement and signal-to-noise performance are significantly improved. The coil is tuned by a mechanism that imparts the same degree of rotation on all of the elements simultaneously, varying their degree of mutual coupling and preserving the overall coil symmetry. A thin radiofrequency shield is an integral part of the coil to reduce the radiation effect, which is a significant loss mechanism at high fields. MR images were collected at 4T using this coil design with high sensitivity and B1 homogeneity. PMID- 7997117 TI - Cholesterol effects on nonelectrolyte membrane transport in human erythrocytes: NMR magnetization transfer studies. AB - The cholesterol content of human erythrocytes was altered by incubating them with sonicated dispersions of cholesterol/phosphatidylcholine at 37 degrees C. 31P NMR saturation transfer experiments were used to measure the rate constant for efflux of dimethyl methylphosphonate (DMMP) from the cells, and thereby gain an estimate of the permeability coefficient. It was shown that up to 39% depletion of membrane cholesterol (cholesterol/phospholipid molar ratio of 0.46) increased the efflux rate constant and permeability coefficient of DMMP 1.55- and 1.86-fold, respectively. Enrichment of the membranes with cholesterol by 45% (cholesterol/phospholipid molar ratio of 1.57) on the other hand, decreased the efflux rate constant and permeability coefficient 1.63- and 1.79-fold, respectively. It was concluded that DMMP may be used as a probe molecule to study the functional consequences of changes in the lipid composition of erythrocytes in diseases that are associated with disorders of lipid metabolism. PMID- 7997116 TI - A four-channel time domain multiplexer: a cost-effective alternative to multiple receivers. AB - The concept of simultaneous image acquisition as originally conceived by Hyde has been implemented by Roemer et al. using a multiple receiver system. This article describes an alternative technique that uses time domain multiplexing (TDM) to acquire simultaneous images using a single receiver channel. This method requires few modifications to the existing receiver and has been shown to be equivalent to a true four channel receiver in most applications. The multiplexing technique was implemented and tested on a standard commercial scanner that has also been equipped with a four channel receiver. Signal-to-noise results demonstrate that four independent images can be multiplexed through a single receiver channel with no degradation in image quality. Additionally, spine images that were obtained from a normal volunteer with both a multiplexed single channel receiver and a true four channel receiver system are presented. PMID- 7997118 TI - In vivo proton magnetic resonance spectroscopy detection of human alcohol tolerance. AB - Alcohol tolerance was ascertained with in vivo proton magnetic resonance spectroscopy (MRS) in men who regularly consumed either large (10-20 drinks/week) or small (2-4 drinks/weeks) amounts of beverage alcohol. Brain ethanol concentrations were determined by MRS, and blood ethanol levels were measured by gas chromatography after controlled ethanol administration (0.8 g/kg). Brain blood ethanol concentration ratios for heavy drinkers were significantly greater than ratios for occasional drinkers (P < 0.002). Inasmuch as ethanol tolerance covaries with the severity of dependence, MRS procedures may facilitate our understanding of alcohol tolerance and treatment of alcoholism. PMID- 7997119 TI - Selective saturation in magnetization transfer experiments. AB - The concept of magnetic saturation in single and binary spin systems is essential to the understanding of magnetization transfer experiments. This paper outlines the requirements for selective magnetic saturation of either of two spin pools contained in a mixture, both having identical chemical shifts. Following a brief discussion of saturation in a homogeneous sample, simple relationships are derived that predict the maximum degree of selective saturation in a two-spin nonexchanging system. Optimal saturation conditions are described in terms of the intrinsic relaxation parameters as well as the experimental conditions of saturation offset frequency and amplitude. In addition, a novel method is proposed that may be applied to saturate the "free" water as opposed to the "bound" water spins in a magnetization transfer experiment. Saturation in an exchanging system is well approximated by these relationships under some physiologically relevant conditions, examples of which are provided. Application of the relationships presented may be useful in the design of experiments to produce maximum magnetization transfer contrast. PMID- 7997120 TI - Electrocardiogram acquisition during MR examinations for patient monitoring and sequence triggering. AB - We have developed a method for measuring the electrocardiogram (ECG) continuously during MR examinations. In contrast to ECG acquisition by wires, our new method is to amplify and convert the ECG into an optical signal directly above the patient's heart. The optical signal is transmitted out of the magnet bore by optical fiber. The small and fixed dimensions of the ECG amplifier avoid interactions with the MR system because of shorter electrical structures and smaller enclosed areas. Tests of the proposed device in a 1.5 Tesla MR system show that continuous and reliable ECG monitoring and sequence triggering are possible. PMID- 7997121 TI - 2D 1H spectroscopic imaging of the human brain at 4.1 T. AB - A two-dimensional spectroscopic imaging sequence consisting of an inversion recovery pulse, a plane selective prefocused pulse, and a semiselective water suppression pulse has been used to create 1H spectroscopic images of the human brain with nominal voxels of 0.5 cc. Due to the excellent lipid suppression provided by the inversion recovery pulse and subsequent delay, only planar volume selection is required enabling the entire brain within the slice to be imaged without contamination from extracerebral lipids in the brain voxels. The use of a semiselective refocusing pulse for water suppression permits any echo evolution time to be used, minimizing J-modulation and T2 losses, while retaining full sensitivity in the lactate resonance. Using this sequence we have visualized the lactate elevation in the peri-infarct region about a 6-week-old stroke. PMID- 7997122 TI - Phase errors in multi-shot echo planar imaging. AB - Field inhomogeneity related phase errors in multi-shot echo planar imaging (EPI) are directly visualized and analyzed in the spatial frequency domain data or 'k space'. The echo time shift (ETS) technique incrementally moves the position of the echo train and improves the phase error function by redistributing phase discontinuities away from the center of k-space. PMID- 7997123 TI - MR gradient echo imaging of intravascular blood oxygenation: T2* determination in the presence of flow. AB - The T2* relaxation time of blood varies with its oxygen saturation. To evaluate the feasibility of imaging intravascular blood oxygenation in humans using a conventional 1.5T MR system, we have implemented a method to measure T2* of blood despite the presence of pulsatile flow. The method was tested in a) stationary and flow phantoms, b) blood samples at different levels of oxygen saturation, and c) a human hypoxia model. Our results demonstrate the ability of cardiac triggered, flow compensated gradient echo imaging to obtain reproducible T2* measurements of flowing blood in vivo. PMID- 7997124 TI - Modeling the effects of patient motion in MRI data acquisition. PMID- 7997125 TI - Trends in pharmacotherapy for chronic airflow limitation in Argentina: 1983-1990. AB - Reported increases in worldwide asthma mortality have prompted the publications of guidelines and consensus statements on the management of airway disease. Overreliance in bronchodilator therapy and lack of anti-inflammatory treatment have been the major findings and the guidelines are aimed at correcting these problems. The Argentinean population appears to have increased prevalence and severity of conditions characterized by chronic airflow limitation and there is no data, to our knowledge, that has analyzed how the treatment of such conditions has been conducted in the past years. Drug sales data in Argentina were surveyed retrospectively to estimate prescriptions dispensed for the treatment of airway disease for the years 1983 to 1990 inclusive. The number of prescriptions of all airway drugs increased significantly (p < 0.01) in the 8-year period except for oral beta 2-agonists and disodium cromoglycate (DSCG). Prescriptions for these agents were 42.7% and 69% less frequent respectively. Thus, oral beta 2-agonists declined from being the single most frequently prescribed class of drugs (40% of prescriptions) in 1983 to the third most frequently prescribed (22%) in 1990. Concurrently, prescriptions of inhaled beta 2-agonists in all forms rose significantly comprising 27% in 1983 and 46% in 1990 becoming the most commonly prescribed airway therapy. Despite this apparent trend away from oral bronchodilator therapy, theophylline prescriptions comprised a significantly higher percentage of prescriptions in 1990 as compared to 1983 (30% vs 20%).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7997126 TI - [Diabetes prevalence in a school population of Avellaneda, Argentina]. AB - An interview system was used to survey 56,199 students in Avellaneda between the ages of 3 and 20 years, representing 60.6% of the population of that age group in the census. The study covered 178 of the 201 pre-schools, grade schools, high schools and special schools in the area. Thirty three diabetic children were identified (18 girls, 15 boys), with a mean of 12.5 years of age. This represents a prevalence of diabetes in the school age population of 0.45/1000 in the 3-12 year old group, 1.25/1000 in the 13-20 year old group, with 0.59/1000 for the total of children surveyed. (93.82 of ascertainement, 95% CI 0.34 to 0.42/1000). Similar figures have resulted from studies in developed countries. The most frequent initial symptoms were the typical ones, with only 15% showing acidosis or diabetic coma as the initiation of the illness. Viral infections and stress appeared to be related to the onset of the disease. Diabetes was in the family history of 48.5% of the diabetic children, and 24.5% of the non-diabetics. The most common diabetic relative was the paternal grandfather. The maternal side showed a higher number of diabetic relatives with preponderance of males. No socio-economic differences were found between diabetics and non-diabetics. PMID- 7997128 TI - [Antigen retrieval by microwave oven with buffer of citric acid]. AB - Microwave oven (mwo) is used to stimulate tissue fixation and to retrieve antigens damaged by fixation. Heavy metal salt solutions, water, and citric acid buffer (cab) have been suggested for this purpose. A serie of tumors treated with cab and phosphate-buffered saline (pbs) with mwo were studied immunohistochemically with 24 antibodies. Controls were treated in the same way, except for microwaving. The antibodies were directed against antigens of the following tumors: breast and prostate carcinoma, carcinoid, lymphoma and melanoma. The results showed that cab enhanced the immunoreactivity of the following antigens: estrogen receptors (AMAC), progesterone receptors (Novocastra), HMB45, vimentin, leukocyte common antigen, PCNA, p53, MIB-1 (Ki-67) and prostatic specific antigen. The antigens that did not improve their immunoreactivity, when compared with the control series were: factor VIII, keratin, Leu 22, L26, neuron-specific enolase, CEA, chromogranin, HBME-1, smooth muscle actin and EMA. Microwaving equally improved protein S100 and desmin either with cab or pbs. The only antigen that improved with pbs was actin. The results with B72.3 and NKI/C3 were poor and not reliable. In conclusion microwaving with cab enhances the immunoreactivity of the antibodies mentioned above leading to an increase in sensibility without loosing specificity. PMID- 7997127 TI - [Risk factors for coronary atherosclerosis. Comparison between two Argentine regions]. AB - The prevalence of risk factors for coronary atherosclerosis were studied in two population samples, Northeast (Posadas, n = 498) and South (Viedma, C. Rivadavia and Cipolletti, n = 652) of 20 years and older, males and females. The diet in the Northeast (n = 102) contained more monounsaturated acids and polyunsaturated acids than the one in the South (n = 62), 9.5 +/- 4.1 vs. 8.1 +/- 3.5% TCV (Total Caloric Value) (P < 0.02) and 8.1 +/- 4.1 vs. 6.2 +/- 3.0% TCV (P < 0.001) respectively. The P/S relationship was greater in the Northeast, 1.02 +/- 0.44 vs. 0.85 +/- 0.50 (P < 0.001). Total cholesterol (TC) in the Northeast was less than in the South, in males 176 +/- 41 vs. 213 +/- 43 mg/dl (P < 0.001); CLDL (LDL cholesterol) 109 +/- 37 vs. 141 +/- 41 mg/dl (P < 0.001). The most frequent risk factors in the South vs. Northeast (males) were: TC > or = 240 mg/dl, 26.7% vs. 9.5% (P < 0.001); LDL-C > or = 160 mg/dl, 30.3% vs. 10.9% (P < 0.001); Cig > or = 10/d (equal or more than 10 cigarettes per day), 30.0% vs. 16.4% (P < 0.001). The hypertension prevalence (HTA, 160/95), in males, was higher in the Northeast than in the South, 23.7% vs. 11.5% (P < 0.001). BMI > 27 Kg/m2 was higher in the women of Northeast than in the South, 38.4% vs. 24.2% (P < 0.001). In the males of the Northeast, the combination Cig > or = 10/d and HTA, 4.1 vs 0.9% was more common; in the South Cig > or = 10/d and LDL-C > or = 160 mg/d, 8.2% vs. 1.8% (P < 0.001) was more common. The differences in the prevalence of the risk factors between the population samples indicate the need to plan the prevention of coronary atherosclerosis locally. PMID- 7997129 TI - [Diagnosis and treatment in general internal medicine. Curriculum selection]. AB - In our country general internists are the providers of adult medical care in urban areas. In the past twenty years, with the increasing subspecialization within internal medicine and the development of advances in technology, the role of the general internist seems to be endangered. Recently much attention has been focused on this area and Divisions and Programs of General Internal Medicine have been established in most medical schools in the USA. The University of Buenos Aires instituted a Program of General Internal Medicine in its major teaching hospital in 1987. One of its purposes was to offer an educational experience to residents in the field of internal medicine primary care. This paper summarizes how this program was carried out and the subjects proposed in the area of Diagnosis and Treatment. The Program of General Internal Medicine is performed in the Outpatient Division and it is staffed by 3 faculty members and 4 fellows. Residents in Internal Medicine have a three month, full-time block rotation in the Program. A young, city dwelling, lower middle class population participates in the Program, with almost 10000 visits a year. The Program offers an experience that includes supervised patient care, an average of 100 office visits a month, and seminars and/or workshops covering topics of "Diagnosis and Treatment", "Case Presentations", "Clinical Epidemiology", "Prevention", and "Doctor-Patient Interview". In the area of Diagnosis and Treatment, the criteria used were: 1 frequency of diagnosis as determined by previous investigations, 2-relevant clinical conditions absent from the frequency list as determined by a consensus process by faculty members.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7997130 TI - [Enzyme replacement therapy in type 1 Gaucher's disease]. AB - Gaucher disease is a sphingolipid storage disorder caused by a deficiency of the lysosomal enzyme glucocerebrosidase (GC) and the consequent deposition of glucocerebrosides into the cells of the macrophagic system. Among the three types of clinical disease, type 1 leads to hepatosplenomegaly, hypersplenism and skeletal abnormalities including bone pain, osteopenia and fractures. Two pediatric female patients with moderately severe type 1 Gaucher disease were treated with commercially available GC, mannose terminated to be macrophage targeted. GC was given by intravenous infusion (30 to 60 units per kilogram of body weight every two weeks) for 8 and 18 months. The hemoglobin concentration increased and the serum acid phosphatase decreased in both patients. In the most affected child, hepatic volume decreased significantly and bony symptoms disappeared. Infusions were uneventful except for an episode of anaphylaxis that subsided rapidly, allowed resumption and did not affect efficacy. These observations are in agreement with the international experience in approximately 800 cases, with good tolerance in all type 1 patients who show objective clinical improvement; patterns of response are variable from patient to patient, independent from previous splenectomy, and dose-dependent; the dose can be tapered after a period of time. Antibodies anti-GC are seen in 13% of the patients, but their presence does not have clinical consequences. The cost of the enzyme makes it crucial to define precise indications, optimal dosing schedules, duration of treatment and cost-benefit ratio. PMID- 7997131 TI - [Kaposi's sarcoma in young adults without evidence of HIV infection]. AB - Besides the AIDS-related form of Kaposi sarcoma (KS) there are few well-known aggressive types of this disease. These non-epidemic invasive variants of KS have been recognized in young black males of equatorial Africa and in renal transplant recipients after iatrogenic immunosuppression. We report on two white patients without known risk factors who presented an invasive clinical form of KS with negative serology for HIV infection. Patient 1: 46 year-old white male of Italian origin without known risk factors. He consulted in September 1990 because of a nephrotic syndrome associated with membranoproliferative glomerulonephritis. On physical examination he presented a violaceous nodule in one toe of the right foot. He received prednisolone with amelioration of the renal disorder, but consulted again some months later because of fever, marked weight loss, generalized enlargement of superficial lymph nodes, autoimmune hemolytic anemia and polyclonal hypergammaglobulinemia. ELISA tests, Western-blot and HIV-antigen investigations were repeatedly negative. CD4 and CD8 counts were 450 and 365 per microlitre respectively. A lymph node biopsy demonstrated KS associated to Castleman's disease. KS was also diagnosed in the skin biopsy. The hemolytic anemia was treated with prednisolone without success and KS cutaneous lesions extended to both legs and ulcerated even after a short course of bleomycin and radiotherapy. The patient died nine months later. Patient 2: 38 year-old white male of German origin, with a history of alcoholism. He was admitted to the hospital because of septic shock associated with hepatic failure. On physical examination he presented ascites, liver and spleen enlargement, and a big subcutaneous nodule on the knee covered with normal skin.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7997132 TI - [Acute extra-axial hematoma post-traumatic of the clivus]. AB - Magnetic Resonance Imaging (MRI) has amply shown its usefulness for the evaluation of traumatic cranio-encephalic lesions, particularly those involving the posterior fossa, due to the absence of bone artifacts, the availability of multiplanar sections and the greater sensitivity as regards Computerized Tomography (C. T.). We present an MRI examination of an extra-axial hematoma of the clivus in a child with head trauma, not visible on C. T. scans. PMID- 7997134 TI - [Partial trisomy of chromosome 15 with new phenotypic manifestations]. AB - A patient with a 15 partial trisomy and a 4 target chromosome in 100% of metaphases is presented. Phenotypic manifestations not previously described were observed such as macrocephally, long face, low implantation of ears, narrow forehead, epicanthal fold, copious eyebrows and synophrys, short nasolabial distance, convergent strabismus, delayed bucal eruption, long neck, hypertrophy of thenar and hypothenar bulging and articular hypermobility. The eyeground was degeneratively myopic. This case makes more extensive the variety of clinical manifestations of this disease. PMID- 7997133 TI - [Small cell pulmonary carcinoma, nephrotic syndrome and kidney failure of rapid evolution]. AB - There are different clinical manifestations and various types of glomerular damages associated to neoplasias. The association to nephrotic syndrome is a relatively frequent event. However, rapidly evolutive renal insufficiency with extensive crescentic glomerulonephritis in more than 50% of the glomeruli is not usually thought to be linked to malignant diseases. We present the case of a previously healthy 55 year old man, who suffered a nephrotic syndrome and renal failure of rapid evolution, in whom a small cell lung cancer was detected. He died in three months and at autopsy mesangial proliferation and enlargement of basal membranes with crescents in 90% of the glomeruli were observed. Electronic microscopy also showed enlargement of the basal membrane. Structures consistent with immune-complex depositions were not seen. We reviewed the reported cases of glomerular lesions and neoplasias, and described the 20 cases published with this particular type of glomerular lesions described for the first time in 1976. None of these 20 cases belongs to this variety of lung cancer. Only in 5 patients, rapidly evolutive renal insufficiency was accompanied by nephrotic syndrome, as in the present case. The presence of immunocomplexes is not frequent and it was mentioned in only four cases. The only three cases of small cell lung carcinoma with nephrotic syndrome described in the literature were associated with membranous glomerulonephritis. PMID- 7997135 TI - [Tumor suppressor genes. New perspectives for clinical investigations in cancer]. AB - Tumor origin is viewed as comprising a series of specific genetic events in target cells and their clonal descendants. The development of molecular biology during the last decade has led to the recognition that these events fall into two distinct categories: the activation of protooncogenes and the inactivation of tumor suppressor genes. The latter are genes the inactivation of which is required for the malignant transformation of a cell. Loss of tumor suppressor genes plays an important role in the development of human tumors. Studies with somatic cell hybrids have shown that tumor suppression occurs in neoplastic cells and can be corrected by cell fusion with normal human chromosome. These experiments proved that tumorigenicity is a recessive phenotype controlled by specific chromosomes. Certain tumor suppressor genes, e.g. p53 and RB1, may be involved in a variety of malignancies whereas others, e.g. the DCC gene, may be restricted to a single type of cancer. The detection of germline mutations in tumor suppressor genes should allow the identification of subjects at high risk of developing cancer. PMID- 7997136 TI - [AIDS: again to basic?]. PMID- 7997137 TI - [Panic crisis. Its identification in clinical office]. PMID- 7997138 TI - [Churchill, Fleming and the penicillins]. PMID- 7997139 TI - [Intravenous clindamycin as monodrug in treatment of 2 patients with toxoplasmic encephalitis]. PMID- 7997140 TI - [Treatment of asthma in Argentina]. PMID- 7997141 TI - [Exacerbation of parkinsonism caused by fluoxetine]. PMID- 7997142 TI - [Unspecific increase of blood levels of angiotensin converting enzyme in chronic hemodialysis]. PMID- 7997143 TI - [Spinal arachnoiditis as complication of peridural anesthesia]. PMID- 7997144 TI - [Tuberculosis and lymphoma]. PMID- 7997145 TI - [Humoral response to mycobacteria in patients with Crohn disease]. AB - The recent recovery of Mycobacterium paratuberculosis from tissues of patients with Crohn's disease has highlighted the possible etiologic role of this microorganism in the disease. However, the immunological evidence generated by various groups supporting this hypothesis is as yet inconclusive. A specific antibody response might be masked in these patients by the wide antigenic homologies prevailing within the genus Mycobacterium. The present study was undertaken with the purpose of exploring the humoral response to M. paratuberculosis in patients with Crohn's disease, by means of a cross-absorption procedure recently proposed for unveiling the presence of specific antibodies in bovine paratuberculosis. Antibodies IgG to M. paratuberculosis were investigated by enzyme-linked immunosorbent assay in 90 serum samples from 17 patients with Crohn's disease, 23 patients with ulcerative colitis an 14 with other bowel diseases. Samples from 86 subjects without bowel disease (healthy individuals and patients with tuberculosis, mycobacterioses and fungal diseases) were also included as controls. The specificity of these antibodies was explored by the absorption of sera with an ubiquitous Mycobacterium (M. phlei). The results were compared to those obtained by similar ELISA tests employing M. avium or M. tuberculosis as antigens. A faint humoral response to M. paratuberculosis and M. tuberculosis was detected in patients with Crohn's disease. Cross-absorption with M. phlei did not disclose a specific response nor was an increase in antibody levels detected in patients studied periodically. Sera from patients with ulcerative colitis and other bowel diseases also showed a slight reaction to mycobacteria.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7997146 TI - [Effect of carbon disulfide on menopause in women]. AB - The authors examined clinically 1710 women. Among them 199 women with symptoms of menopause were selected and divided into two groups: group I (control) included 80 women without contact with carbon disulphide and group II (examined) included 119 women chronically exposed to carbon disulphide at a concentration of 9.36 23.4 mg/m3. Menopause was present in 16.59% of women chronically exposed to CS2 as compared with 8.05% of the normal population. The mean age at menopause was 48.1 years in group I and 43.9 in group II. Significantly more frequent headaches, weight gain and loss of libido (p < 0.01) were observed in women chronically exposed to CS2. While in the control group fatigue, palpitations and hot flushes were more often (p < 0.001). The concentrations of estrone (p < 0.01), estradiol, progesterone, 17-hydroxy-progesterone, testosterone and dehydroepiandrosterone sulphate (DHAS) were significantly decreased in women chronically exposed to CS2 (p < 0.001). No difference in the level of dehydroepiandrosterone was found. The daily excretion of adrenaline and noradrenaline in urine and concentrations of dopamine in plasma of women chronically exposed to CS2 were lower (p < 0.001), while the concentrations of serotonin and prolactin in plasma were higher (p < 0.001). No differences in the level of FSH or LH were noted between the two groups. Significant negative linear correlations between serotonin and FSH (r = -0.45; p < 0.01) serotonin and daily excretion of adrenalin (r = -0.43; p < 0.01) or noradrenalin (r = -0.58; p < 0.001) were found in the exposed group.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7997148 TI - [Characteristic features of workers' exposure at the carbon black factory in Gliwice "Carbochem"]. AB - The "CARBOCHEM" is one of the two carbon black factories in Poland. The hygienic studies revealed high concentrations of total dust with no more than 2% of free silica. Carbon black in the air exceeded many times the MAC values. The results of medical examinations will be presented in subsequent papers. PMID- 7997147 TI - [Occupational contact dermatitis induced by allergens present in rubber. II. allergy to antioxidants]. AB - Out of 339 persons suffering from occupational dermatitis, the group of 51 patients (15%), allergic to rubber, were eligible for the study. The frequency of allergy to amine compounds and quinoline derivatives (8 chemical compounds), used in rubber mixtures to prevent rubber oxidation, was investigated. The group under study comprised of 20 workers of the metallurgic, 6 of the building and 3 of the rubber industries as well as 15 health service workers, 2 farmers and 5 drivers. Allergy to amine compounds was found in 30 persons (58.8%) and to quinoline derivatives in 5 persons (9.8%). N-isopropyl-N-phenyl-4-phenylenodiamine proved to be most allergenic (52.9% of allergic persons), then N-cyclohexyl-N-phenyl-4 phenylenodiamine (31.4%) and N,N-diphenyl-4-phenylenodiamine (23.5%). Allergy to amine antioxidants was two times higher among workers of the metallurgic and building industries as well as among farmers and drivers than in health service workers, and it was induced by contact with technical rubber. PMID- 7997149 TI - [The circulatory system in workers involved in carbon black production]. AB - Carbon black is a commercial product manufactured under controlled conditions. It is not considered as a carcinogenic substance. It is even assumed that it reduces considerably carcinogenesis of substances adsorbed on its surface. The aim of the study was to present the condition of the circulatory system of workers involved in the carbon black production. The study covered the group of exposed persons (n = 118) and the control group (n = 241). The results of environmental studies indicated excess of dust MAC values at work posts. It was concluded that exposure to carbon black was harmful to health of workers employed in its production, especially in the case of a long-term exposure to dust concentrations exceeding MACs. Hypertension occurs more frequently in persons exposed, and smoking proved to be an additional pathogenic factor affecting health of this group of workers. Pathogenesis of hypertension is unknown and investigations should be continued. PMID- 7997150 TI - [Problem of noise in production sections of dairies in Poland]. AB - This paper reports the study of noise levels in three production sections- cottage cheese, cheese and butter--at 14 dairies in 7 regions (vovoidships) of Poland. Measurements were carried out in dB(A) and dB(Lin) and the octave analysis was performed within the range of 31.5-8.000 Hz. It was found that the cottage cheese and butter sections proved to be the source of harmful effect on workers' hearing while the cheese section did not present any danger. PMID- 7997152 TI - [Preliminary assessment of the nervous system of workers in view of current propositions and methods]. PMID- 7997151 TI - [Epidemiologic methods for evaluating the effects of occupational exposure on pregnancy outcome]. AB - Methodological problems of epidemiological studies of the effect of harmful factors present in the working environment on the reproduction and development of the progeny were discussed. Basic types of epidemiological studies such as retrospective and prospective cohort studies, cross-sectional and case-control studies were presented. Issues pertaining to the measurement bias and its sources in individual types of studies were raised. An appropriate selection of measures illustrating disturbances in the reproduction and development of the progeny was considered as well as adapted definitions of those measures and their correct classification. ahe methodology of an appropriate assessment of exposure to harmful factors in the working environment was also discussed. PMID- 7997153 TI - [The role of pulmonary epithelial cells in lung cellular reaction to asbestos exposure]. AB - The damage of pulmonary alveolar epithelial cells occurs in many inflammatory conditions caused by various agents, e.g. asbestos, that involve interstitial lung disease in experimental animals and in humans. After exposure to asbestos alveolar epithelial cells contain significant amount of asbestos fibers and show histologic changes which indicate a marked epithelial injury. The alveolar epithelial injury is manifested by swelling, debris and patchy necrosis of type I cells partly detached from its basement membrane. Besides, regenerative hyperplasia of type II pneumocytes with ultrastructurally cisternal dilation of the rough endoplastic reticulum and significantly greater number of lamellar bodies are found. Following the cessation of exposure, epithelial cells are cleared out of asbestos fibers and return to the normal condition. These data provide insight into pathogenesis of diffuse lung disease and the role of alveolar cells in early and late phases of asbestosis. PMID- 7997154 TI - [Section of occupational hygiene in the state sanitary inspection service- organizational situation-personnel and activities in 1993]. AB - The authors discuss the organization, staff matters and activities of the occupational hygiene section of the Polish sanitary and epidemiological services in 1993. The analysis is based on reports produced by the Ministry of Health (form MZ-50), descriptive reports and inspections at occupational hygiene sections. The authors focused on these three components as they give rise to many problems and difficulties, particularly in regard to monitoring of working places. An attempt is also made to suggest solutions to certain problems. The need for training of persons involved in occupational hygiene as well as for developing different forms of upgrading professional qualifications among workers with secondary education is emphasized. PMID- 7997155 TI - [Kazimierz Karaffa-Korbutt (1878-1935) physician--hygienist]. AB - During the years 1918-1921 Kazimierz Karaffa-Korbutt -- a physician-hygienist worked as a professor of the Piotrograd University, then he moved to Vilnus where the lectured at the S. Batory University. The creator of the Polish school of experimental hygiene who also laid the foundations of the industrial hygiene. The author of the first school and university textbooks on hygiene as well as of many publications in the area of hygiene, among them works on occupational, military and social hygiene deserve a special mention. In 1925 he founded and edited the first scientific journal devoted to hygienic issues entitled "Archiwum Higieny". He was a member of numerous national and international scientific associations. In 1932 he became a member of the Polish Academy of Learning. PMID- 7997156 TI - Bees aren't the only ones: swarming in gram-negative bacteria. AB - Swarming is a form of active surface motility that is widespread among flagellated, Gram-negative bacteria. In the laboratory, growth of the bacteria on certain agar surfaces leads to induction of the differentiated swarmer-cell state. Swarmer cells are generally long and multinucleate, always hyperflagellated, and can move rapidly over the agar surface in a coordinated manner. Some swarm colonies exude large amounts of 'slime', which could be essential for promoting intimate cell-cell contacts during swarming. There is evidence that the differentiated swarmer-cell stage facilitates pathogenic associations with host tissue. Almost nothing is known about the molecular signalling mechanism of surface sensing. Increased viscosity appears to be sensed by several bacteria, but other environmental cues, specific to each bacterium, are also important. In organisms in which swarming motility has been studied in some detail, the chemotaxis system has been shown to play an important role. The recent discovery of swarming motility in two genetically well-characterized organisms--Escherichia coli and Salmonella typhimurium--should lead to rapid progress in understanding this process. PMID- 7997157 TI - The actin-based motility of the facultative intracellular pathogen Listeria monocytogenes. AB - The Gram-positive bacterium Listeria monocytogenes is a facultative intracellular parasite that invades and multiplies within diverse eukaryotic cell types. An essential pathogenicity determinant is its ability to move in the host cell cytoplasm and to spread within tissues by directly passing from one cell to another. The propulsive force for intracellular movement is thought to be generated by continuous actin assembly at the rear end of the bacterium. Moving bacteria that reach the plasma membrane induce the formation of long membranous protrusions that are internalized by neighbouring cells, thus mediating the spread of infection. The unrelated pathogens Shigella and Rickettsia use a similar process of actin-based motility to disseminate in infected tissues. This review focuses on the bacterial and cellular factors involved in the actin-based motility of L. monocytogenes. PMID- 7997158 TI - Sequence changes in the pilus subunit lead to tropism variation of Neisseria gonorrhoeae to human tissue. AB - Pili of Neisseria gonorrhoeae are correlated with increased bacterial attachment to epithelial cells and undergo both phase and antigenic variation. Phase variation of gonococcal pili can be brought about by recombination events in the pilin structural gene, pilE, or by the on/off switch in expression of PilC, a pilus biogenesis protein for which two loci exist. We have studied the binding to epithelial cell lines and to fixed tissue sections of N. gonorrhoeae MS11 derivatives and mutants carrying structurally defined PilE and PilC proteins. In situ binding studies of N. gonorrhoeae to formalin-fixed tissue sections resulted in a binding pattern similar to that obtained using viable epithelial cell lines of different origin. Piliated gonococcal clones, containing different pilE sequences, varied dramatically from one another in their efficiencies at binding to corneal and conjunctival tissue, but bound equally well to cervical and endometrial tissues. Further, the binding data suggested that PilC expression by itself, i.e. without pili, cannot confer bacterial binding and that expression of either PilC1 or PilC2 does not confer different binding properties to the bacterial cells. Possible receptors for piliated gonococci were expressed in human tissues, such as cervix, endometrium, cornea, intestine, stomach, mid-brain and meninges, but not in human kidney. Pretreatment of the target tissues with Proteinase K decreased the gonococcal binding dramatically, whereas pretreatment with neuraminidase and meta-periodate, which cleave carbon-carbon linkages between vicinal hydroxyl groups in carbohydrates, did not affect attachment of gonococci. These data argue that pilus-dependent attachment of N. gonorrhoeae to human tissue may be mediated by a eukaryotic receptor having protein characteristics, and that the pilus subunit sequence may play an important role in the interaction with human cornea. PMID- 7997159 TI - Identification of a second oligopeptide transport system in Bacillus subtilis and determination of its role in sporulation. AB - Sporulation in Bacillus subtilis depends on an intact oligopeptide transport system, the Opp system. Mutants in opp sporulate poorly but second-site revertants can be found that restore sporulation and peptide transport. These second-site mutations were found in a second oligopeptide transport system, app, in which the peptide-binding protein, AppA, is mutant owing to a frame-shift mutation, and the revertants restore the original frame. The AppA mutation is present in the 168 strain of B. subtilis. The app operon consists of five genes in the order appD-appF-appA-appB-appC, with the locus designations corresponding to their homologue in the opp operon. Homology between the app and opp proteins ranges from 54% identity for AppF and OppF, to 22% identity for AppA and OppA. Both the App and Opp permease systems can transport tetra- and pentapeptides, but tripeptides are not transported by the App system. Strains of the genotype app+ opp- are resistant to the tripeptide antibiotic bialaphos. The repaired App system can substitute completely for the Opp system in both sporulation and competence for genetic transformation. The phenotypes raised some speculation about the subunit configuration of the Opp system. PMID- 7997160 TI - Transmembrane signal transduction by the Escherichia coli osmotic sensor, EnvZ: intermolecular complementation of transmembrane signalling. AB - The Escherichia coli regulatory proteins, EnvZ and OmpR, are crucially involved in expression of the outer membrane proteins OmpF/OmpC in response to the medium osmolarity. The EnvZ protein is presumably a membrane-located osmotic sensor (or signal transducer), which exhibits both kinase and phosphatase activities specific for the OmpR protein. To examine the functional importance of the membrane-spanning segments (named TM1 and TM2) of EnvZ molecules in transmembrane signalling, a set of EnvZ mutants, each having amino acid substitutions within the membrane-spanning regions, was characterized in terms of both their in vivo phenotype and in vitro catalytic activities. One of them, characterized further, has an amino acid change (Pro-41 to Ser or Leu) in TM1, and appeared to be defective in its phosphatase activity but not in its kinase activity. This EnvZ mutant conferred a phenotype of OmpF-/OmpC-constitutive. For this EnvZ(P41S or P41L) mutant, a set of intragenic suppressors, each exhibiting a wild-type phenotype of OmpF+/OmpC+, was isolated. These suppressor mutants were revealed to have an additional amino acid change within either TM1 or TM2. Furthermore, they exhibited restored phosphatase activity (i.e., both kinase+ and phosphatase+ activities). It was further demonstrated that one of the suppressors, EnvZ(Arg 180 to Trp in TM2), was able to suppress the defects in both the in vivo phenotype and the in vitro catalytic activities caused by EnvZ(P41S), through intermolecular complementation. These results are best interpreted as meaning that an intimate intermolecular interaction between the membrane-spanning segments of EnvZ is crucial for transmembrane signalling per se in response to an external osmotic stimulus. PMID- 7997162 TI - The protein HU can displace the LexA repressor from its DNA-binding sites. AB - The major bacterial histone-like protein HU is a small, basic, dimeric protein composed of two closely related subunits. HU is involved in several processes in the bacterial cell such as the initiation of replication, transposition, gene inversion and cell division. It has been suggested that HU could introduce structural changes to the DNA which would facilitate or inhibit the binding of regulatory proteins to their specific sites. In this study we investigated the effect of HU on the binding of LexA protein, the regulator of SOS functions, to three of its specific binding sites. We show that HU can displace LexA from its binding sites on the operators of the lexA, recA and sfiA genes. The lexA operator was the most sensitive while the higher affinity sfiA operator was the least sensitive. Since HU, like its homologue IHF, probably binds DNA in the minor groove we tested the effect of distamycin, a drug which binds to the minor groove, on LexA binding. Like HU, this drug disrupted LexA-operator complexes. These results suggest that distortion of the minor groove of the lexA operators excludes the binding of the repressor to the major groove. PMID- 7997161 TI - EGTA induces the synthesis in Escherichia coli of three proteins that cross-react with calmodulin antibodies. AB - Escherichia coli mutants, (verA, dilA) specifically resistant to the Ca2+ channel inhibitors verapamil and diltiazem, respectively, are hypersensitive to EGTA and BAPTA. We have shown, using 1-D and 2-D gel electrophoresis, that the synthesis of at least 25 polypeptides in the mutants was enhanced by treatment with Ca2+ chelators and the synthesis of at least 11 polypeptides was repressed. This pattern of induction was not observed in heat- or SDS-treated cells and therefore does not appear to be a general stress response. The majority of the induced proteins are low molecular weight, extremely heat stable and acidic, characteristic properties of calmodulin. Moreover, of the major induced species, three with apparent molecular masses of 12, 18, and 34 kDa all cross-reacted with polyclonal and monoclonal antibodies to eukaryote calmodulins or calerythrin, a heat-resistant Ca(2+)-binding protein from Saccharopolyspora erythraea. The verA, dilA mutants, in being hypersensitive to EGTA and to the Ca2+ ionophore A23187 + Ca2+, may be defective in the regulation of the level of free intracellular Ca2+. PMID- 7997163 TI - Neither absence nor excess of lambda O initiator-digesting ClpXP protease affects lambda plasmid or phage replication in Escherichia coli. AB - Owing to rapid proteolysis of the coliphage lambda-coded initiator protein, lambda O, this protein is considered to carry a rate-limiting step in lambda DNA replication. The discovery of ClpXP protease responsible for lambda O protein turnover allowed an opportunity to verify this hypothesis. However, neither absence nor excess of this protease significantly affected the transformation efficiency and copy number of lambda plasmid, or the kinetics of the lambda phage growth. These results are also incompatible with the hypothesis that the stabilization of lambda O plays a role in the switch from early (circle-to circle) to late (rolling-circle) lambda phage DNA replication. Transcriptional activation of ori lambda, probably assisted by the Escherichia coli DnaA function, remains as the possible rate-limiting step in lambda DNA replication. PMID- 7997165 TI - Analysis of membrane protein interaction: ToxR can dimerize the amino terminus of phage lambda repressor. AB - The ToxR protein of Vibrio cholerae is an integral membrane protein that co ordinately regulates virulence determinant expression. ToxR directly activates the cholera toxin operon, but maximal activation is achieved in the presence of ToxS, an integral membrane protein thought to interact with ToxR periplasmic sequences. Studies that substitute alkaline phosphatase sequences for the periplasmic domain of ToxR have led to a model for ToxR activation based on dimerization and ToxS interaction. We constructed lambda-ToxR chimeric proteins using the DNA-binding domain of the phage lambda repressor, which cannot effectively dimerize by itself, to assess the ability of ToxR to form dimers in Escherichia coli. The results suggest that ToxR sequences can propagate dimerization, and that ToxS can influence the ability to dimerize. PMID- 7997164 TI - An analogue of the DnaJ molecular chaperone whose expression is controlled by sigma s during the stationary phase and phosphate starvation in Escherichia coli. AB - The Escherichia coli CbpA protein appears to be an analogue of the molecular chaperone, DnaJ, as judged from not only its structure but also its possible function. The expression of cbpA, however, was not significantly affected by up shift of the growth temperature. Remarkably, it was found that the expression of cbpA was induced under certain growth conditions, such as the entry of cells into stationary phase, or growth in a phosphate-limited medium. Such conditional expression of cbpA was regulated at the transcriptional level in a sigma s dependent manner. The structure of this sigma s-dependent cbpA promoter was clarified by determining its transcription start site. The cbpA promoter region was found to contain an unusual DNA structure (i.e. DNA curvature). From these results, it was suggested that, in contrast to DnaJ, CbpA may function as a molecular chaperone in an adaptive response to environmental stresses other than heat shock. PMID- 7997166 TI - A dominant mutation in the bacteriophage lambda S gene causes premature lysis and an absolute defective plating phenotype. AB - The S and R genes of the bacteriophage lambda are required for lysis of the host. R encodes 'endolysin', a soluble transglycosylase which accumulates in the cytoplasm during late protein synthesis. S encodes a 'holin', a small membrane protein which, at a precisely scheduled time, terminates the vegetative cycle by forming a lethal lesion in the membrane through which gpR gains access to the peptidoglycan. A missense allele of S, Ala52Gly, causes lysis to occur prematurely at about 19-20 min after induction of a lysogen, compared to 45 min for the wild type. This allele has a severe plaque-forming defect which appears to be entirely a consequence of the early lysis and resultant severe reduction in particle burst size. The early-lysis phenotype is dominant and is aggravated, in terms of an even more reduced burst size, at both 30 degrees C and 42 degrees C. The mutation maps in the middle of a putative membrane-spanning helical domain of S, near the sites of other S- mutations with recessive non-lytic phenotypes. The mutation has no effect on S-protein accumulation or on the ratio of S107 and S105 products in the membrane. The mutation appears to affect the intrinsic timing function by which the S protein controls the lysis schedule. PMID- 7997167 TI - Regulation of xylose utilization in Bacillus licheniformis: Xyl repressor-xyl operator interaction studied by DNA modification protection and interference. AB - Xylose utilization in Bacillus licheniformis is inducible by xylose. We establish here that the Xyl repressor recognizes and binds an xyl operator sequence located 12 nucleotides downstream from the transcription start site of the xyl operon. DNA-retardation experiments employing xyl regulatory DNA and soluble protein extracts indicate complex formation in the presence of Xyl repressor. Two repressor-operator complexes are distinguished by different gel mobilities. They yield the same in situ copper-phenanthroline footprint. This result suggests that a single xyl operator may be bound by different oligomers of Xyl repressor. Methylation and hydroxyl radical cleavage protection of the xyl operator by Xyl repressor binding and ethylation interference of Xyl repressor binding to the xyl operator reveals symmetrical interaction of the repressor with two half sites of the operator, which show palindromic symmetry and are located on the same side of the B-form DNA structure. PMID- 7997168 TI - Identification of a partition region carried by the plasmid QpH1 of Coxiella burnetii. AB - Coxiella burnetii is an intracellular bacterial pathogen which causes Q fever in humans and other animals. Most of the isolates found carry plasmids which share considerable homology. Unfortunately all of these plasmids remain cryptic. Initial attempts to look for secreted or membrane proteins encoded by these plasmids using TnphoA mutagenesis revealed an open reading frame on the EcoRI fragment C of the plasmid QpH1. Upstream DNA sequencing of the TnphoA insertions revealed a deduced peptide sequence with homology to the SopA protein which is encoded by the F plasmid in Escherichia coli. Maxicell analysis showed that fragment C encoded two proteins: one was 43.5 kDa in size and designated QsopA, and a second was 38 kDa in size. These proteins are similar in molecular weight to the SopA and SopB proteins, which are essential components of the partition mechanism of the F plasmid. The region appears to be conserved in plasmids QpRS, QpDV, and QpDG, but is absent in a plasmidless isolate in which plasmid sequences have integrated into the chromosomal DNA. Complementation studies demonstrated that fragment C has a plasmid partitioning function and can restore maintenance stability of the partition-defective mini-F plasmid. These data suggest that fragment C carries the plasmid partition region of the plasmid QpH1. PMID- 7997169 TI - The Salmonella typhimurium invasion genes invF and invG encode homologues of the AraC and PulD family of proteins. AB - We have identified two novel Salmonella typhimurium genes, invF and invG, which are required for the efficient entry of these organisms into cultured epithelial cells. invF and invG are located immediately upstream of invE, a previously identified gene also required for Salmonella entry. Non-polar mutations in these genes rendered S. typhimurium severely deficient for entry into cultured epithelial cells. The nucleotide sequences of invF and invG indicated that these genes encode polypeptides with predicted molecular weights of 24,373 and 62,275, respectively. Proteins of similar sizes were observed when invF and invG were expressed in a bacteriophage T7 RNA polymerase-based expression system. Comparison of the predicted sequence of InvF with translated sequences in the existing databases indicated that this protein is homologous to members of the AraC family of prokaryotic transcription regulators. However, mutations in invF did not significantly affect the expression of other members of the inv locus. InvG was found to be homologous to members of the PulD family of specialized translocases. This homology suggests that InvG may be necessary for the export of invasion-related determinants or involved in the assembly of a supramolecular structure that promotes entry. PMID- 7997170 TI - Location of a lepidopteran specificity region in insecticidal crystal protein CryIIA from Bacillus thuringiensis. AB - The Bacillus thuringiensis insecticidal crystal protein CryIIA has both high mosquito activity and gypsy moth activity; in contrast CryIIB, which is 87% homologous, displays no mosquito activity and has a three-fold lower gypsy moth activity. The regions responsible for specificity against gypsy moth (Lymantria dispar) and mosquito (Aedes aegypti) larvae were located by introducing MluI and XhoI sites into homologous positions within the putative domain II of both cryIIA and cryIIB genes, which divided almost equally the respective second domains into three regions. Taking advantage of naturally occurring NheI and NarI sites that border the putative domain II, a set of seven chimeric proteins were produced by exchanging all combinations of those regions between CryIIA and CryIIB. Analysis of the toxicity of these chimeric proteins demonstrated that the lepidopteran and dipteran specificity regions of CryIIA were not colinear. While the specificity region of CryIIA against mosquito larvae involved region 1 and probably also region 2, the specificity region of CryIIA against gypsy moth larvae was located within region 2. PMID- 7997171 TI - Five Listeria monocytogenes genes preferentially expressed in infected mammalian cells: plcA, purH, purD, pyrE and an arginine ABC transporter gene, arpJ. AB - Listeria monocytogenes is a bacterial pathogen that multiplies within the cytosol of eukaryotic cells. To identify Listeria genes with preferentially intracellular expression (pic genes), a library of Tn917-lac insertion mutants was screened for transcriptional fusions to lacZ with higher expression inside a macrophage-like cell line than in a rich broth medium. Five pic genes with up to 100-fold induction inside cells were identified. Three of them (purH, purD and pyrE) were involved in nucleotide biosynthesis. One was part of an operon encoding an ABC (ATP-binding cassette) transporter for arginine. The corresponding mutants were not affected in intracellular growth, cell-to-cell spread or virulence, except for the transporter mutant, whose LD50 after intravenous infection of mice was twofold higher than the wild-type. The fifth gene was plcA, a previously identified virulence gene that encodes a phosphatidylinositol-phospholipase C, and is cotranscribed with prfA, a gene encoding a pleiotropic transcriptional activator of known virulence genes. Although plcA expression is known to depend on PrfA, a prfA promoter-lacZ fusion was highly expressed both inside and outside cells. Furthermore, in the presence of cellobiose, a disaccharide recently shown to repress plcA and hly expression, plcA and hly mRNA levels were dramatically reduced without any decrease in the monocistronic prfA mRNA levels. These results demonstrate that virulence gene activation does not depend only on prfA transcript accumulation. PMID- 7997172 TI - Mutational analysis of the arginine repressor of Escherichia coli. AB - Arginine biosynthesis in Escherichia coli is negatively regulated by a hexameric repressor protein, encoded by the gene argR and the corepressor arginine. By hydroxylamine mutagenesis two types of argR mutants were isolated and mapped. The first type is transdominant. In heterodiploids, these mutant polypeptides reduce the activity of the wild-type repressor, presumably by forming heteropolymers. Four mutant repressor proteins were purified. Two of these map in the N-terminal half of the protein. Gel retardation experiments showed that they bind poorly to DNA, but they could be precipitated by L-arginine at the same concentration as the wild-type repressor. The other two mutant repressors map in the C-terminal half of the protein. They are poorly precipitated by L-arginine and they bind poorly to DNA. In addition, one of these mutants appears to exist as a dimer. The second type of argR mutant repressor consists of super-repressors. Such mutants behave as arginine auxotrophs as a result of hyper-repression of arginine biosynthetic enzymes. They map at many locations throughout the argR gene. Three arginine super-repressor proteins were purified. In comparison with the wild-type repressor, two of them were shown to have a higher DNA-binding affinity in the absence of bound arginine, while the third was shown to have a higher DNA-binding affinity when bound to arginine. PMID- 7997173 TI - Mutant Escherichia coli arginine repressor proteins that fail to bind L-arginine, yet retain the ability to bind their normal DNA-binding sites. AB - The Escherichia coli arginine repressor (ArgR) is an L-arginine-dependent DNA binding protein that controls expression of the arginine biosynthetic genes and is required as an accessory protein in Xer site-specific recombination at cer and related recombination sites in plasmids. Site-directed mutagenesis was used to isolate two mutants of E. coli ArgR that were defective in arginine binding. Results from in vivo and in vitro experiments demonstrate that these mutants still act as repressors and bind their specific DNA sequences in an arginine independent manner. Both mutants support Xer site-specific recombination at cer. One of the mutant proteins was purified and shown to bind to its DNA target sequences in vitro with different affinity and as a different molecular species to wild-type ArgR. PMID- 7997174 TI - Redundancy of the conserved His residue in Azotobacter vinelandii NifL, a histidine autokinase homologue which regulates transcription of nitrogen fixation genes. AB - The NifL protein of Azotobacter vinelandii inhibits NifA, the activator of nif (nitrogen fixation) transcription, in response to oxygen and fixed nitrogen. NifL shows strong homology in its C-terminal domain to the histidine autokinase domains of the canonical two-component sensor proteins, including the region around His-304, which corresponds to the residue known to be phosphorylated in other systems. To examine the mechanism of sensory transduction by NifL, mutations encoding 10 substitutions for His-304 were introduced into the A. vinelandii chromosome. Regulation of nif transcription was measured using acetylene reduction and RNA blots. The substitutions His-304-->Arg and His-304- >Pro impaired regulation by both fixed nitrogen and oxygen, but substitution of Ala, Phe, Ile, Lys, Asn, Ser, Thr, Val had no effect. None of the mutants, including His-304-->Arg and His-304-->Pro, excreted ammonium during diazotrophy, a phenotype of nifL deletion mutants, suggesting that the molecular basis of this effect differs from that responsible for the inhibition of nif transcription. The data show conclusively that phosphorylation of His-304 is not essential for any of the known functions of A. vinelandii NifL. Homology to the family of histidine autokinases is therefore inadequate evidence for a mechanism of sensory transduction involving phosphorylation of the conserved histidine residue. PMID- 7997175 TI - Partial suppression of an Escherichia coli TonB transmembrane domain mutation (delta V17) by a missense mutation in ExbB. AB - Active transport of vitamin B12 and Fe(III)-siderophore complexes across the outer membrane of Escherichia coli appears to be dependent upon the ability of the TonB protein to couple cytoplasmic membrane-generated protonmotive force to outer membrane receptors. TonB is supported in this role by an auxiliary protein, ExbB, which, in addition to stabilizing TonB against the activities of endogenous envelope proteases, directly contributes to the energy transduction process. The topological partitioning of TonB and ExbB to either side of the cytoplasmic membrane restricts the sites of interaction between these proteins primarily to their transmembrane domains. In this study, deletion of valine 17 within the aminoterminal transmembrane anchor of TonB resulted in complete loss of TonB activity, as well as loss of detectable in vivo crosslinking into a 59 kDa complex believed to contain ExbB. The delta V17 mutation had no effect on TonB export. The loss of crosslinking appeared to reflect conformational changes in the TonB/ExbB pair rather than loss of interaction since ExbB was still required for some stabilization of TonB delta V17. Molecular modeling suggested that the delta V17 mutation caused a significant change in the predicted conserved face of the TonB amino-terminal membrane anchor. TonB delta V17 was unable to achieve the 23 kDa proteinase K-resistant form in lysed sphaeroplasts that is characteristic of active TonB. Wild-type TonB also failed to achieve the proteinase K-resistant configuration when ExbB was absent. Taken together these results suggested that the delta V17 mutation interrupted productive TonB-ExbB interactions. The apparent ability to crosslink to ExbB as well as a limited ability to transduce energy were restored by a second mutation (A39E) in or near the first predicted transmembrane domain of the ExbB protein. Consistent with the weak suppression, a 23 kDa proteinase K-resistant form of TonB delta V17 was not observed in the presence of ExbBA39E. Neither the ExbBA39E allele nor the absence of ExbB affected TonB or TonB delta V17 export. Unlike the tonB delta V17 mutation, the exbBA39E mutation did not greatly alter a modelled ExbB transmembrane domain structure. Furthermore, the suppressor ExbBA39E functioned normally with wild type TonB, suggesting that the suppressor was not allele specific. Contrary to expectations, the TonB delta V17, ExbBA39E pair resulted in a TonB with a greatly reduced half-life (approximately 10 min). These results together with protease susceptibility studies suggest that ExbB functions by modulating the conformation of TonB. PMID- 7997177 TI - Use of digitized video microscopy with a fluorogenic enzyme substrate to demonstrate cell- and compartment-specific gene expression in Salmonella enteritidis and Bacillus subtilis. AB - A rapid and sensitive method for detection of cell- and compartment-specific gene expression in individual cells of both Gram-negative and Gram-positive microorganisms is described. The method combines the use of gene fusions to lacZ, and a fluorogenic beta-galactosidase substrate, fluorescein-di-(beta-D galactopyranoside), with digitized video microscopy. All of the reporter constructs tested were successfully detected. Secondary staining of the cells with a nucleic acid-specific dye, propidium iodide, allowed cells devoid of nucleic acid to be identified, while cell nucleoid shape and the morphological stage of development could be correlated with the location of beta-galactosidase activity. The double-staining procedure was used to show that gene expression can be induced in non-culturable cells of Salmonella enteritidis produced by carbon/nitrogen starvation. The resolution was sufficient to distinguish between cells at different morphological stages of sporulation in Bacillus subtilis. This highly sensitive and rapid method may have many other applications in basic and applied microbiology. PMID- 7997176 TI - Cloning and primary structure of Staphylococcus aureus DNA topoisomerase IV: a primary target of fluoroquinolones. AB - A 4.6 kb Staphylococcus aureus DNA fragment containing DNA gyrase-like genes (grlA and grlB) was cloned and sequenced. The proteins GrlA and GrlB exhibit more than 30% identity with E. coli DNA topoisomerase IV subunits and with the gyrase subunits from S. aureus and Escherichia coli. The combined E. coli cell extracts of GrlA and GrlB overproducing strains catalysed ATP-dependent relaxation and decatenation specific to DNA topoisomerase IV. The temperature-sensitive phenotype of Salmonella typhimurium parC and parE mutants was complemented by the S. aureus grlA and grlB genes, when the two genes were co-expressed. These results show that GrlA and GrlB are the subunits of S. aureus DNA topoisomerase IV. The GyrA subunit of DNA gyrase has been previously defined as a primary target of quinolones based on genetic and biochemical experiments essentially carried out in E. coli. Single-point mutations occurring in the 'quinolone resistance-determining region' (QRDR) of GyrA were found in bacteria exhibiting quinolone resistance, the most common mutation being a substitution of Ser-83 on the E. coli GyrA sequence. We analysed eight S. aureus fluoroquinolone-resistant clinical isolates and observed that mutations in the QRDR of GyrA are not present in the low-quinolone-resistant isolates. In contrast, Ser-80 of GrlA, which corresponds to Ser-83 of E. coli GyrA, is substituted to Phe or Tyr in both high- and low-quinolone-resistant isolates. We propose that DNA topoisomerase IV is a primary target of fluoroquinolones in S. aureus. PMID- 7997178 TI - Fluctuations in glycolytic mRNA levels during morphogenesis in Candida albicans reflect underlying changes in growth and are not a response to cellular dimorphism. AB - The levels of pyruvate kinase (PYK1), alcohol dehydrogenase (ADH1), phosphoglycerate kinase (PGK1) and phosphoglycerate mutase (GPM1) mRNAs were measured during batch growth and during the yeast-to-hyphal transition in Candida albicans. The four mRNAs behaved in a similar fashion. PYK1, ADH1, PGK1 and GPM1 mRNA levels were shown to increase dramatically during the exponential growth phase of the yeast form, and then to decrease to relatively low levels in the stationary phase. The dimorphic transition was induced using two sets of conditions: (i) an increase in temperature (from 25 degrees C to 37 degrees C) combined with the addition of serum to the medium; and (ii) an increase in temperature (from 25 degrees C to 37 degrees C) and an increase in pH of the growth medium (from pH 4.5 to pH 6.5). Additional cultures were analysed to control for the addition of serum, and for changes in temperature or pH. Immediately following dilution of late-exponential cells into fresh media the levels of all four glycolytic mRNAs decreased rapidly in contrast to the ACT1 mRNA control, the level of which increased under most conditions. The recovery of glycolytic mRNA levels depended on the culture conditions, but there was no direct correlation with the formation of germ tubes, with the addition of serum to the medium, the increase in culture temperature, the medium pH, or the glucose concentration. This indicates that the changes in glycolytic gene expression that accompany the dimorphic transition in C. albicans reflect the underlying physiological status of the cells during morphogenesis and not alterations to cell shape. PMID- 7997179 TI - The fimbrial gene cluster of Haemophilus influenzae type b. AB - Haemophilus influenzae infections are preceded by airway colonization, a process facilitated by fimbriae. Here, we identified the complete fimbrial gene cluster of H. influenzae type b. HifA forms the major subunit. HifB, a periplasmic chaperone, and HifC, an outer membrane usher, are typical assembly genes; their inactivation abolished fimbriae formation. HifD and HifE are putative minor subunits, both participating in fimbriae biogenesis. Inactivation of either one drastically reduced fimbriae expression. HifD represents a novel type of fimbrial subunit with lipoprotein characteristics, pointing to a membrane-associated function of HifD. Transcription of all fimbrial genes is coregulated through two clustered promoters. The flanking of the fimbrial gene cluster by repetitive extragenic palindromic sequences together with a partial duplication of an adjacent unrelated operon indicated that the cluster was once inserted in the H. influenzae genome as a mobile virulence unit. PMID- 7997180 TI - Identification of an HP1 phage protein required for site-specific excision. AB - Transposon insertion mutagenesis and transformation were used to locate genes responsible for excision in the temperature phage HP1 of Haemophilus influenzae. A 6.5 kb segment of DNA near the left end of the phage genome was sequenced, and 11 new open reading frames were identified. Two face-to-face overlapping promoter sequences organized these open reading frames into two operons transcribed in opposite directions. Interruption of the first open reading frame in the rightward operon created lysogens unable to produce phages. Provision of the uninterrupted open reading frame in trans restored phage production. The gene identified by this procedure, cox, was cloned and the protein product was expressed at high levels in Escherichia coli. The Cox protein is a 79-residue basic protein with a predicted strong helix-turn-helix DNA-binding motif. Extracts induced to express high levels of Cox contained a 9 kDa protein. These extracts inhibited integrative recombination and were required for excisive recombination mediated by HP1 integrase. The HP1 cox gene location is similar to that of the homologous excisive and regulatory genes from coliphages P2 and 186. These phages appear to share a distinctive organization of recombination proteins and transcriptional domains differing markedly from phage lambda and its relatives. PMID- 7997181 TI - The pigmentation locus of Yersinia pestis KIM6+ is flanked by an insertion sequence and includes the structural genes for pesticin sensitivity and HMWP2. AB - The pigmentation (Pgm+) phenotype of Yersinia pestis includes a number of different characteristics which appear to be associated with a 102 kb segment of chromosomal DNA known as the pgm locus. In Y. pestis KIM6+, the pgm locus is flanked by direct copies of a repeated element that probably plays a role in the spontaneous deletion of this region. We have sequenced the ends of these elements and shown that they have features in common with bacterial insertion sequences. In addition we show that a clone, pSDR498, from the pgm locus of KIM6+ restores pesticin sensitivity and the iron-regulated expression of three polypeptides, 240 kDa, 190 kDa, and 68 kDa in size, to Pgm- cells. In vitro transcription/translation assays and Escherichia coli minicells were used to analyse the products encoded by various subclones of pSDR498. Pesticin sensitivity mapped to a 5.9 kb fragment that encodes a 68 kDa protein derived from a 72 kDa precursor. Synthesis of the 190 kDa protein was restored by a 19.2 kb clone, indicating that the structural gene for this protein also resides within the pgm locus of Y. pestis KIM6+. Finally, a survey of our Pgm- strains indicates that 97% have also deleted the sequences encoding the 190 kDa protein and pesticin sensitivity. PMID- 7997182 TI - A novel illegitimate recombination event: precise excision and reintegration with the Mu gem mutant prophage. AB - The bacteriophage Mu is known to insert its DNA more or less randomly within the Escherichia coli chromosome, as do transposable elements, but unlike the latter, precise excision of the prophage, thereby restoring the original sequence, is not observed with wild-type Mu, although it has been reported with certain defective mutants. We show here that the mutant prophage Mu gem2ts can excise precisely from at least three separate loci -- malT, lac and thyA (selected as Mal+, Lac+ and Thy+, respectively). This excision occurs under permissive conditions for phage development, is observed in fully immune (c+) lysogens, and is independent of RecA and of Mu transposase. Mu gemts2 excision is invariably accompanied by reintegration of a Mu gem2ts prophage elsewhere in the chromosome. In the case of Mal+ revertants, this prophage is systematically located at 94 min on the E. coli chromosome. Mu gem2ts excision therefore sheds some light on the long-standing paradox of the lack of precise Mu excision. PMID- 7997183 TI - Transport of haemin across the cytoplasmic membrane through a haemin-specific periplasmic binding-protein-dependent transport system in Yersinia enterocolitica. AB - The Yersinia enterocolitica O:8 periplasmic binding-protein-dependent transport (PBT) system for haemin was cloned and characterized. It consisted of four proteins: the periplasmic haemin-binding protein HemT, the haemin permease protein HemU, the ATP-binding hydrophilic protein HemV and the putative haemin degrading protein HemS. Y. enterocolitica strains mutated in hemU or hemV genes were unable to use haemin as an iron source whereas those mutated in the hemT gene were able to use haemin as an iron source. As Escherichia coli strains expressing only the haemin outer membrane receptor protein HemR from Y. enterocolitica were capable of using haemin as an iron source the existence of an E. coli K-12 haemin-specific PBT system is postulated. The first gene in the Y. enterocolitica haemin-specific PBT system encoded a protein, HemS, which is probably involved in the degradation of haemin in the cytoplasm. The presence of the hemS gene was necessary to prevent haemin toxicity in E. coli strains that accumulate large amounts of haemin in the cytoplasm. We propose a model of haemin utilization in Y. enterocolitica in which HemT, HemU and HemV proteins transport haemin into the cytoplasm where it is degraded by HemS thereby liberating the iron. PMID- 7997186 TI - Patients, not nurses or physicians, must come first. PMID- 7997184 TI - The nlpD gene is located in an operon with rpoS on the Escherichia coli chromosome and encodes a novel lipoprotein with a potential function in cell wall formation. AB - rpoS is the structural gene for sigma s, which is a second vegetative sigma subunit of RNA polymerase in Escherichia coli and is involved in the expression of many stationary phase-induced genes. Upstream of rpoS is an open reading frame (ORF) whose function and regulation have not been studied. Strong overproduction of its gene product using the IPTG-inducible tac promoter leads to the formation of bulges at the cell septum and the cell poles, and in rapidly growing cells brings about cell lysis, indicating that the gene product has a hydrolytic function in cell wall formation or maintenance. This is corroborated by sequence homology to lysostaphin, a cell wall lytic exoenzyme synthesized by two Staphylococcus strains. Using globomycin, a specific inhibitor of signal peptidase II, we demonstrate that the product of the ORF is a novel lipoprotein (NlpD). Two transcriptional start sites for nlpD have been localized. In contrast to rpoS, nlpD is not induced during entry into stationary phase. Growth-phase regulated transcription of rpoS is initiated at additional sites within the nlpD ORF, but the nlpD promoters contribute substantially to the basal level of rpoS expression in exponentially growing cells, indicating that nlpD and rpoS form an operon. PMID- 7997185 TI - Galactose-binding site in Escherichia coli heat-labile enterotoxin (LT) and cholera toxin (CT). AB - The galactose-binding site in cholera toxin and the closely related heat-labile enterotoxin (LT) from Escherichia coli is an attractive target for the rational design of potential anti-cholera drugs. In this paper we analyse the molecular structure of this binding site as seen in several crystal structures, including that of an LT:galactose complex which we report here at 2.2 A resolution. The binding surface on the free toxin contains several tightly associated water molecules and a relatively flexible loop consisting of residues 51-60 of the B subunit. During receptor binding this loop becomes tightly ordered by forming hydrogen bonds jointly to the GM1 pentasaccharide and to a set of water molecules which stabilize the toxin:receptor complex. PMID- 7997187 TI - Health care reform--a community-based alternative: the comprehensive community health models initiative. PMID- 7997188 TI - Cell immortalization enhances Listeria monocytogenes invasion. AB - Recent outbreaks of human listeriosis have emphasized the importance of food in the etiology of epidemic listeriosis, suggesting that the gastrointestinal tract is the natural site of entry for Listeria monocytogenes into the organism. L. monocytogenes invasion of finite cell lines derived from the porcine ileum exhibited a 100-fold lower penetration level, without any intracellular multiplication, when compared to CaCo-2 cells, a widely used in vitro model for L. monocytogenes invasion. Same results were obtained with both pig kidney primary cells and mouse kidney finite cell lines. To demonstrate that cell immortalization enhances L. monocytogenes invasion, finite cell lines from porcine ileum and from murine kidney were immortalized by Simian virus 40 (SV40) large T oncogene. Unlike their untransformed counterparts, the immortal cells obtained were invaded by L. monocytogenes, as observed for CaCo-2 cells as well as for spontaneously immortal human (HeLa) and murine (3T3) cell lines. Extensive electron microscopy examinations of porcine epithelioid cells infected by L. monocytogenes showed numerous bacteria within the immortal cells, whereas neither intracellular bacteria nor any bacterial antigen were revealed inside finite cell lines. These data suggested that L. monocytogenes were not destroyed inside finite cell lines but only poorly entered the finite or primary cells. Speculating that L. monocytogenes invasion is under control of differentiation or proliferation of the cells, only an enterocyte subset at a defined state of differentiation or expressing particular receptors could be invaded in vivo. PMID- 7997189 TI - Correlation between hepatitis B viremia and the clinical and histological activity of chronic delta hepatitis. AB - To analyze the serological, clinical and histological significance of hepatitis B virus (HBV) replication among a group of patients with chronic delta hepatitis (CDH), we have studied the clinical and the histological activity in 49 patients with CDH. The HBV-DNA was analyzed by dot-blot and polymerase chain reaction (PCR). Concomitant infection with hepatitis C virus (HCV) was analyzed by reverse transcriptase (RT)-PCR, HDV replication by dot-blot, and human immunodeficiency virus (HIV) infection by enzyme-linked immunosorbent assay. The subjects were divided into three groups according to HBV-DNA status: group I: 14 patients HBV DNA dot-blot positive; group II: 29 patients HBV-DNA positive only by PCR, and group III: 6 patients HBV-DNA negative by dot-blot and PCR. We have found HBV-DNA by dot-blot in 28.5% of patients, and by PCR in 87.7%. Also 22 patients were anti HCV positive (86.3% had HCV-RNA by RT-PCR). The first group (HBV-DNA dot-blot positive) had significantly higher serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) than those in the second and third groups. Likewise, serum ALT and AST were significantly higher in the second group (HBV DNA positive by PCR) than in those of the third group. Histological inflammatory activity was significantly higher in the group of patients with HBV-DNA detectable by dot-blot. The prevalence of serum HDV-RNA and IgM anti-HDV were similar in the three groups. These results were similar in the anti-HCV-positive and -negative patients. In conclusion, these data suggest that: (1) persistence of HBV replication is a major determinant of severe liver damage in chronic delta hepatitis, and (2) HCV and HIV infections do not influence the natural history of CDH. PMID- 7997191 TI - [The effect of homocarnosine on neuronal activity during satiation and starvation]. AB - We investigated effects of homocarnosine (gamma-aminobutyric-histidine) dipeptid on neuron nucleus caudatus and hypocampus activity in small and hungry experimental animals--awake grown-up rabbits. In the given conditions, through glass microelectrodes having several channels, an extracellular registration of impulse discharge was performed as well as the microapplication of homocarnosine (HC) in the immediate surroundings of registered neurons. The obtained results show that the investigated different functional conditions of the organism are manifested in the neurons' activity of the investigated brain structures. Homocarnosine represses the activity of most registered neurons in both satiated and hungry experimental animals, while that effect is more manifested in satiated animals. The demonstrated effects of homocarnosine point to its probable neuromediator role. PMID- 7997190 TI - Human T helper cells reactive with somatic bacterial antigens belong to the Th1 subset. AB - The aim of this study was to characterize the cytokine secretion patterns of human T helper cells from healthy donors reactive with somatic antigens from various bacteria, the nematode Anisakis and tetanus toxoid. From the peripheral blood of four healthy donors we have established 70 T cell lines reactive with antigens from Yersinia, Salmonella, Morganella, Klebsiella, Serratia, Escherichia, Chlamydia, Shigella, Streptococcus, tetanus toxoid and Anisakis, respectively. Our results show that all T cells reactive with bacteria produce interferon-gamma (IFN-gamma) and tumor necrosis factor-alpha (TNF-alpha), but no interleukin (IL)-4 and no or very little IL-2 and IL-10 and, thus, belong to the Th1 subset, while T cells reactive with tetanus toxoid or Anisakis belong to the Th0 subset with production of IFN-gamma, IL-2, IL-4, IL-10 and TNF-alpha. In summary, our data further substantiate the concept of a functional diversity of human T helper cells with respect to their cytokine profiles. Furthermore, they indicate that a Th1 cytokine profile is not restricted to intracellular bacteria. PMID- 7997192 TI - [Standards and criteria in histologic intraoperative diagnosis in the lymph nodes]. AB - Using frozen sections and classic paraffin sections of the lymph nodes, comparative diagnostic analysis was done in the patients with differently localized malignant tumours. The analysis was based on 86 patients with malignant tumours mostly localized in the maxillofacial region. The frozen sections diagnoses are divided into "metastasing carcinoma in the lymph node", "reactive lymphadenitis", "malignant", "benign", "malignant lymphoma" and "normal lymph node". Diagnostic reproducibility on the level of 90% cases using classic sections was estimated. Negative results in 10% were discussed and some recommendations for improvement of the 9:1 relation were done. PMID- 7997193 TI - [Morphologic asymmetry of the frontal lobe of the cerebral hemisphere in man]. AB - The morphology and the left-right asymmetry of the frontal lobe convexity (sulcus frontalis superior and inferior, sulcus precentralis, gyrus precentralis, gyrus frontalis superior and medius) were studied on 19 formaline fixed human brains. During the study, the gyral and sulcal patterns were marked as similar, partially similar or different. Sulcal patterns on the left and right side were completely different (in at least more than half) in the greatest number of cases. Gyral patterns were also asymmetric (mirror image analysis). However, using the "essential gyral line"--the line indicating longitudinal gyral axis--the results changed dramatically. The majority of patterns appeared to be very similar, indicating that the method of analysis largely influences the results of morphological studies of human brain asymmetry. This explains different findings reported in the literature. We suggest that the use of the "essential gyral line" provides standardized method of morphological analysis, which was not available up to date. PMID- 7997194 TI - [Morphologic characteristics and static resistance of transplanted patellar ligaments after replacement of the cruciate ligaments in the knee--an experimental study in a dog]. AB - An experimental study on transplantation validity of patella's ligament, when transplanting front crossed ligament, was performed on 106 knees in 53 grown-up dogs. The investigation had three stages. Three months after the transplantation of the front crossed ligament with the medial third part of the patella's ligament animals were sacrificed and in one group the static resistance and the resistance to elongation, by using special tweezers (Alfred Amsler Co., Schafhausen, Switzerland), was investigated. The results showed that the patella's ligament is very suitable for transplantation because its resistance and strength were almost identical with the same parameters of intact front crossed ligament. Revascularization of the new ligament using Spaltenholz's technique was done in the second group, and three months after the operation, complete revascularization of transplants took place. The synovial membrane which covers the new ligament represents the main source of fresh blood vessels on one side, while similar process takes place along the bone tunnels where the new ligament was fixed. The new ligament histologic analysis carried out in the third group of experimental animals showed that after three months the transplant acquires the structure which is very similar to the front crossed ligament. The obtained results of the investigation show that the patella's ligament is a very good biologic material for transplantation of the crossed ligament. PMID- 7997195 TI - [Case report of familial generalized neurofibromatosis (von Recklinghausen disease)]. AB - The authors made a report on a case of generalized neurofibromatosis (GN) in a patient, 21 years old, and her father, 59 years old, pointing to the family character of illness. They especially emphasized the presence of numerous family disseminated tumors of the neurofibroma type, on the skin of the torso and extremities, as well as the presence of simultaneous combination of these tumors with pigmented skin of the naevi spili (cafe au lait) type. In the reported cases no damages on other systems and organs have been found. Reports on such cases from the clinical practice may be important for education of young physicians of different medical fields. PMID- 7997196 TI - [Thrombophlebitis in the minor pelvis in problems with differential diagnosis in gynecologic oncology]. AB - The oncologic-gynecology practice shows that vein thrombophlebitis of the pelvis minor causes retroperitonal spreading of malignant tumor of the cervix or growth of the ovarian neoplasm. In cases of unexplained etiology, the existance of malignant tumors as an etiologic factor, should be excluded by the examination performed by an experienced gyneocologist-oncologist, by ultrasonography, computerized tomography and in case of doubt by explorative laparotomy. PMID- 7997197 TI - [Use of the hybridization in situ method in the detection of human papillomaviruses in female genital tumor tissue]. AB - We review preliminary results obtained by use of this diagnostic procedure- hybridization in situ for diagnosis of human papilloma virus in bioptic material of anogenital tract in women. Of 11 examined bioptic specimens, we found positive hybridization signal on "test" groups HPV 6, 11 and HPV 16, 18. This is the first report on papilloma virus in women from the territory of Vojvodina. PMID- 7997198 TI - [Attempted suicide as a reflection of adolescent crisis]. AB - Adolescence is a transitory period in the process of maturation of an individual and, as such, is often accompanied by conduct disorders and different crisis manifestations. These crises often result in suicide attempts which have all the characteristics of an "appeal function". In our group of 200 suicide attempts, we compared the group of adolescent to the group of adult suicide attempts. The comparison was based on a series of different sociodemographic and psychopathological characteristics (e.g. sex, presence of "broken home", method of attempt, family history of psychiatric illness, current psychiatric diagnosis). The results show statistically significant differences between the two groups in relation to some of the characteristics. The paper attempts to explain those differences. Overall results also show that adolescents may be considered as suicide risk group which demands our full attention, particularly from the preventive point of view. PMID- 7997199 TI - [Survival of patients with planocellular bronchial carcinoma who were treated conservatively and with surgery]. AB - The paper presents the analysis of survival rate among 133 patients with squamous cell bronchial carcinoma during the five-year follow-up period, from 1985 to the end of 1989, treated at the Institute of Pulmonary Diseases and Tuberculosis in Belgrade. Duration of the survival was monitored in four therapeutical groups: B1 (surgically treated - 34 cases), B2 (conservatively treated using combined chemotherapy and irradiation therapy - 44 cases), B2-1 (treated with only chemotherapy - 32 cases) and B2-2 (treated with only irradiation therapy--23 cases). Maximal survival among the patients with squamous cell bronchial carcinoma was evidenced in surgically treated group of patients (8.8% survived for 5 years). Conservative therapy achieved three-year survival in 4.5% of group B2 patients and 9.4% of group B2-1 patients. Minimum survival was recorded in patients treated with a single irradiation therapy with maximal duration of 2 years achieved in 4.3% of cases. The mean duration of survival ranged from 28.1 +/- 15.2 months in group B1, being similar in groups B2 and B2-1 (15.3 +/- 8.0 and 15.1 +/- 8.2 months, respectively), while it was the least in the group B2-2: 8.8 +/- 6.4 months. Variance analysis revealed highly significant statistical difference in mean duration of survival among the patients with squamous cell bronchial carcinoma classified in different therapeutical groups (F = 107.783; p < 0.0001). PMID- 7997200 TI - [The role of toxocariasis in the etiology of hypereosinophilic syndrome in children]. AB - Toxocariasis as a helminth zoonatroponosis is very common in dogs in our region, thus the infestation of human population, especially children, is frequent, 59 children with high blood eosinophilia, aged 18 months to 14 years, were examined on toxocariasis by indirect immunofluorescence test, 23 children were positive, with antibody titre 1:20-640. Dominant symptoms and signs were cough, allergic exantemas, lymphadenopathy and leucocytosis. One child had eosinophilic meningitis. Some of these children were addicted to geophagia, particularly those with clinical picture corresponding to toxocariasis. The original antigen for the indirect immunofluorescent antibody assay was made of mice brains previously infected with high dose of toxocara larvae (6000 per mouse). Two or three months later, mice were sacrificed and their brains were fixed and included in paraffin wax. Histological sections were used as antigen for titration of patient's serum samples. Authors conclude that all eosinophilias in children should be examined serologically for toxocariasis. PMID- 7997201 TI - [The role of ultrasonography in the diagnosis of enlarged parathyroid glands]. AB - The ultrasonographic diagnosis of parathyroid glands was introduced by the Japanese in 1975. Only after more perfect machines have been introduced, first of all by advancement of "real-time" technique, this method started being used as a routine. The paper shows results of ultrasonographic investigation in 200 patients separated into two groups. In the first group 100 patients were examined with a clinical suspect of primary hyperparathyroidism from which in 30 the existence of parathyroid gland adenoma was diagnosed. Scintigraphy of parathyroid glands was performed in the smaller group of patients; the comparison of these two methods was done, and in 77.7% cases coincidence was found. In the group of 10 operated patients comparison of the two mentioned methods was carried out, with surgical or pathohistologic findings and the coincidence was complete. In the second group 100 patients were examined belonging to the chronical program of hemodialysis, from which in 24 cases existence of swollen parathyroid glands was found. Comparison of ultrasonographic and scintigraphic findings was also done and the coincidence was 68.75%. At the end, the importance of ultrasonography in the first diagnostic stage of swollen parathyroid glands was pointed out. PMID- 7997202 TI - [Evaluation of the effect of therapy with Turganil in 1,240 patients]. AB - The paper deals with results of investigation on therapy efficiency of tiaprophenic acid (Turganil, Jugoremedia) in the group of 1240 outpatients and hospitalized patients. It was an open clinical experiment, the drug has been applied for six months approximately, and the group consisted of patients with inflammatory, degenerative and outjoint rheumatism and other systemic diseases of the connective tissue. Favorable therapy effects occurred in all investigated groups, being in harmony with other authors' data, while drug tolerance was relatively good. PMID- 7997203 TI - [Evaluation of the reliability of endogenous creatinine clearance as in indicator of renal function in ambulatory patients. I]. AB - Clearance of the endogenous creatinine is a simple method for application, it is relatively cheap and applicable in almost all surroundings, but it is not reliable enough when the obtained results are concerned. This report shows the results of determining this clearance in comparison with radiosotope clearance 51 cr-EDTA, referent for clinical research, in 52 outpatients with primary and secondary kidney diseases. It was found that values of clearance of the endogene creatinine (Clkr) are significantly lower than the clearance 51 Cr-EDTA (ClEDTA) (t = 2.391, p < 0.01) and that the correlation between the two method is poor (r = 0.688). The source of mistakes should be looked for (and strictly controlled) when gathering diuresis, because the biochemical method of creatnine concentration determination of the biologic material itself is reliable enough. PMID- 7997204 TI - [Salivation in the submandibular salivary gland in the prognosis of peripheral facial nerve paralysis. Clinical study]. AB - The relationship between the quantitative submandibular gland secretion and neural motor function was examined in 157 patients with different types of peripheral facial paralysis. These two functions were followed up during the period of one year. In the patients with 40%, or more, of submandibular gland secretion one month after the onset of facial paralysis, the motor nerve function recovery was satisfactory, while, in the patients with submandibular gland secretion less than 20% the recovery was unsatisfying. When the submandibular gland secretion was more than 50% in the early stage of facial paralysis, the complete recovery was within 6 months. On the contrary, when it was less than 50%, the recovery period was much longer. PMID- 7997205 TI - [Rubella in Vojvodina. VI. Serologic status of women of reproductive age during the time of endemic manifestations of rubella 1978-1985]. AB - In first phase of a study on congenital Rubella syndrome incidence in Vojvodina population, we examined serologic status of 1225 non-pregnant and 846 pregnant women of generative age, as well as the level of exposure to the Rubella virus. On the basis of antihemagglutinin antibody titre 93.2% of women were found to have antibody titre level above or equal to 1/8. There were no significant differences between the proportions of seropositive women in different age groups (x2 = 1.20; P = 0.88). The percentage of seropositive women varied from 82 to 97% (x2 = 29.85; P = 0.005), according to the year of the investigation. The lowest percentage was registered (1980). Rubella virus susceptibility index was 13.1%. On the basis of proven seroconversion the examination of even Rubella serum samples showed the morbidity rate of 7.18%. The level of exposure of pregnant women to the Rubella virus was 71.0%, during all the period of pregnancy. In such circumstances total Rubella morbidity of pregnant women was 2.13%; the highest level, 21%, was in persons form 18 to 19 years of age. It was not possible to make an analysis of pregnancy outcomes and the consequences in pregnant women. PMID- 7997206 TI - [Use of the modified Warthin-Starry method in pigmented nevi of the skin]. AB - Warthin-Starry method is an argyrophilic method, performed at ph 3.2. It is a very efficient method for demonstration of melanin pigment granules in the nevus tissue and in malignant melanoma. We have concluded that it is highly specific for demonstration of melanin pigment granules, and more efficient than the Fontan Masson method. The Fontan-Mason method reduces other pigments in the cell, apart from melanin. Modified Warthin-Starry method at ph 3.2 in the nevus tissue reduces only melanin pigment granules. PMID- 7997207 TI - [Vascular characteristics of the lamina terminalis of the human hypothalamus]. AB - The aim of the study is to discover the sources of vascularization, vascular area, the size and density of the capillary network of the vascular organ of the laminae terminalis of the hypothalamus. The brain blood vessels under examination were filled with a mixture of India ink and gelatin. The serial paraffin sections of 30 and 200 um were cleared after Spalteholz. In the vascularization of this neuroendocrine structure of the hypothalamus, two arterial stems take part with their branches: a cerebri anterior and a. communicans anterior. In order to quantify the density of the capillary network, the authors used standard stereologic parameters - volumene density, surface density and mean radius of blood vessels. While the precise functions of the vascular organ have yet to be fully elucidated, the similarity in organization of this region to the median eminence has led several authors to suggest a neurosecretory role for the vascular organ of the lamina terminalis. PMID- 7997208 TI - [Quantitative analysis of gallbladder function using quantitative dynamic radionuclide cholecystography]. AB - The aim of the study is to demonstrate general function of the cholecyst through selected quantitative parameters derived from the quantitative radionuclide cholecystography method, using our own computer software HIDATA, and to evaluate values of specific quantitative parameters in 15 patients presenting with chronic calculous and 15 with chronic acalculous cholecystitis. A control group comprised 10 subjects with no changes on the cholecyst. Of four quantitative parameters calculated during cholecyst filling, the only significant one was the ascending segment slope of the curve from specific ROI, that is, K1 derived from it, because it shows its functional status, depending on the changes in its wall and the lumen content. The most significant parameters which maintain motor function of the cholecyst are ejection fraction (EF) and ejection rate (ER) which are always decreased in chronic cholecystitis, regardless of the presence of calculosis and the number of calculi in the lumen. The ejection fraction is especially decreased in the multiple sclerosis group; it is significantly decreased when compared with acalculous chronic cholecystitis. Our results indicate that a selection of parameters used in clinical practice for the assessment of the cholecyst function is necessary. Our program HIDATA included a large number of parameters of which three were classified as important for the assessment of the cholecyst function (K1, EF, ER), reflecting the process of filling and emptying of the cholecyst and offering reliable and valuable data for the treatment. PMID- 7997209 TI - [Idiopathic histiocytosis of the jaw]. AB - Principal features of Idiopathic Histiocytosis (IH) are discussed in relation to five cases treated in the Department of Maxillofacial Surgery VMA. Clinical symptoms of the disease are known. Radiology of the bones and bone scintiscans are of most importance for evaluation of extension of the disease. Surgery is treatment of choice. The major problem with IH in the jaws is, however, progressive mutilation of dental apparatus. PMID- 7997211 TI - [Clinical use of octreotide (Sandostatin) in endocrinology]. AB - Octreotide is a synthetic octapeptide somatostatin analogue which has higher potency and longer duration of action than the natural hormone. It is effective after subcutaneous administration and no rebound hypersecretion has been observed. Pharmacological effects of octreotide include inhibition of numerous hormones (growth hormone, TSH, insulin, glucagon and all gut hormones), of exocrine secretion (gastric acid, pancreatic enzyme), and of small-bowel absorption. This review deals with clinical application of octreotide in endocrine disorder. In patients with acromegaly octreotide treatment results in decrease of growth hormone (GH) and IGF-I together with tumour shrinkage and clinical improvement. Although variability in response to treatment is obvious for majority of patients the most effective dose is 100 mcg three times daily subcutaneously. Normalization of GH levels could be achieved in more than 50% of treated patients. It has also been shown that octreotide could be effective in TSH secreting pituitary adenoma, ACTH secreting adenoma as well as in non secretory pituitary tumours. A marked biochemical and clinical responses together with longer survival have been reported in most of the patients with gastroenteropancreatic (GEP) tumours. Patients who benefit the most from octreotide therapy are those with carcionid syndrome (successful control of diarrhoea, flushing episodes and wheezing) and VIPomas (control of diarrhoea). In patients with insulin-dependent diabetes mellitus (IDDM) octreotide suppresses GH levels, postprandial blood glucose increases with resultant decrease in daily insulin requirements. In women with polycystic ovary syndrome (PCOS) octreotide has inhibitory effect on serum LH and ovarian androgens. This could have beneficial effect on ovulatory performance in women with PCOS. PMID- 7997210 TI - [Pulmonary neuroblastoma--a rare type of manifestation]. AB - We report a case of pulmonary manifestation of neuroblastoma, one of the most common malignant, solid tumors in children. Diagnostic approach and results of a combined cytostatic therapy are described. The nature of the tumor makes prognosis unpredictable. PMID- 7997212 TI - [Knowledge, attitude and practice in school children regarding traffic accident injuries]. AB - Injuries caused by accidents are great problem in our country as in the rest of the world. Most of the accidents strike children, teenagers and youngsters. The aim of this study was to investigate knowledge, attitudes and practice of schoolchildren regarding traffic and accidents. The children of III, IV, VII and VIII class in elementary school were interviewed by questionnaire. The great number of interviewed children didn't know enough about the traffic rules although they are active participants in traffic as bicyclists and pedestrians. Most of the accidents can be avoided and therefore prevention is important. PMID- 7997213 TI - [Propofol in general anesthesia in children]. AB - For a long period of time propofol has been in use for total intravenous anesthesia in adults. In our literature there are no data on the use of propofol in pediatric anesthesia. The aim of the study was to compare effects of propofol for the induction of anesthesia, maintenance and recovery after anesthesia, with barbiturate, that is, inhalation anesthesia during spontaneous breathing. 50 children underwent propofol anesthesia. A control group comprised 50 children who underwent thiopentone and halothane anesthesia. The average propofol dose was 2.38 mg/kg/tt. Monitoring of cardiovascular parameters revealed statistically significant variations in systolic and diastolic pressure in both groups, but a more significant decrease was recorded in the propofol group. The decrease, recorded only during the initiation of anesthesia, stabilized afterwards. Side effects (pain during the initiation, apnea, spontaneous movements) were present in the propofol anesthesia, while in the halothane group they were reduced. In the propofol group period of recovery was short, indicating advantages of this anesthetic in day care centers. PMID- 7997214 TI - [Sensorineural impairment in the inner ear in epidemic parotitis]. AB - During morbilli and mumps, classical forms of acquired deafness develop in childhood. The aim of the study was to investigate effects of mumps virus on cochlear function. Of 237 examined patients 71 had parotitis and 166 meningitis meningoencephalitis. Audiometric analyses were carried out at the beginning of the treatment and after 6 months. Hearing loss above 30 dB was found in 109 patients (45.99%). Mild hearing impairment of sensorineural type was registered in the majority of patients, while total one-sided hearing loss was found in 2.53% of subjects. No correlation between clinical manifestations of parotitis or meningoencephalitis and hearing loss was found. Cytochemical liquor levels did not influence the development of hearing loss. 6 months later a recovery followed mainly in patients with mild impairments. PMID- 7997215 TI - [Discitis after lumbar diskectomy]. AB - The aim of this study was to examine the frequency and clinical course for early diagnosis (earlier signs-index of suspicion, later signs) and different clinical presentation of disctitis at deep infection wound (DIW) and superficially infection wound (SIW). The medical histories of adult patients, which were all hospitalized after lumbar discectomy at the Department of Rehabilitation during a 5-year period (1986-1990) was retrospectively analysed. The incidence of discitis by 231 patients was 0.43%. DIW 0.43%, and SIW 0.86% is incidence by 231 patients. Infection group with seven patients (three discitis, two DIW, two SIW) and control seria of 52 patients (to be clinically satisfactory) was studied in detail, to the clinical presentation. The most consistent clinical signs at previous diagnosis all patients with discitis, beside 1) delayed strong back pain and 2) erythrocite sedimentation rate (ESR) highly elevated (near 50) in week 2, is 3) increasing course of ESR from week 2 to 4, postoperatively. On the contrary, all patients with DIW and SIW had an decreasing course of ESR from week 2 to 4, postoperatively. ESR of all patients with DIW > 50 < SIW on week 2 postoperatively, which is important for their differentiation along with local signs of the wound. The later signs for diagnosis and differentiation of all patients with discitis from DIW and SIW are typical radiographic findings on discitis, and duration of ESR normalization, beside other signs here analyzed. PMID- 7997216 TI - [Analysis of the relation between socioeconomic factors and suicidal behavior]. AB - The paper explores case histories of 128 patients hospitalized for suicide attempts at the Institute of Neurology, Psychiatry and Mental health in Novi Sad for a period of two years. The analysis of relevant suicidological data was carried out with the aim of determining the significance which SOCIOECONOMIC factors play in gene-rating suicidal behavior. Under the item "occupation/employment" most frequent were "workers" 21.88 per cent, followed by unemployed persons--17.19 per cent, while those on social welfare constituted 16.4 per cent. Financial poverty as the motive for suicide attempt is most often encountered among unemployed ones and those on social welfare. In the total sample, this poverty was registered in 19 cases (14.84 per cent). It is interesting that this motive is more often present in younger persons, where mean age for those on social welfare is 28 and for the unemployed ones is 29 years. The diagnosis most often found in these groups is "Adjustment Disorder with Depressed Mood (309.00)", no psychotic episodes were found. With respect to alcohol dependence, it is much less present among those on social welfare than in the rest of the sample. Therefore, financial poverty is not negligible factor of suicide risk. This finding directly confirms that financial poverty as suicide generator has so far not been researched sufficiently or is evidently on the rise, at least in our society. PMID- 7997217 TI - [Contact allergic dermatitis caused by plants]. AB - In order to contribute to the setting of an accurate diagnosis and prophylaxis of phytodermatitis (PD) and to better understand eczematogenic characteristics of some plants, we present results of an allergologic analysis and review the plants which most commonly cause FD in our material. A total of 15 patients presenting with FD was examined. In all the cases we used a standard technique, patch test (PT); in cases supsective of contact urticaria syndrome (CUS) we used open PT, while photo PT was used for cases suspective of photo PD. We used fresh parts of the plants and standard allergen battery for epicutaneous testing (Department of Immunology, Zagreb). Depending on the profession of the subjects, tests with the material from working places with specific batteries of tests for specific professions were applied according to the recommendations of ICDRG. Tests with parts of the plants were carried out in 8 cases and in 5 controls. A total of 38 plants was examined. Positive PT was found for sisal, willow, parsnip, carrot, celery, spinach, green tomato, broomcorn, lemon skin, pyracantha, arborvitae, yucca, ficus, juniper tree, plane tree and greenhouse grass. In cases of positive PT for willow, carrot, celery, green tomato and grass, positive PT for Peru balsam (PB) was also detected, while in positive PT for lemon skin, a positive PT on turpentine was found as well. Negative results of PT for willow, carrot, celery, parsnip, green tomato, lemon and juniper tree and positive photo PT on greenhouse grass in controls, indicate that we have detected allergic PD on the above mentioned plants. PMID- 7997218 TI - [Anatomic and functional asymmetries in humans]. AB - In this study the authors discuss anatomical and functional asymmetries at the man, i.e. in human kind. They stress that asymmetries exist at the cell level as well, then at the chromosomic one, as well as on all other cells of human organism (cells of blood, liver, lungs, muscles, central nervous system, etc.) They point out to the asymmetries off the central nervous system, autonomous nervous system, as well as to certain organs and organic systems and body parts (head, face, extremities, trunk, etc.) A special attention is devoted to the functional asymmetries at which the emphasis is given to motoric, sensorial and psychic asymmetries. PMID- 7997219 TI - "The high cost of dying" revisited. AB - This review of the literature of the past decade on medical care costs at the end of life finds that the data do not support the often-voiced hypothesis that the rise in medical care costs is due largely to the disproportionate use of high technology medical care by persons who die. It also shows that although the intensity of care, as indicated by hospital expenditures, declines with age, any savings on hospital costs of very old decedents are offset by nursing-home costs. Studies of hospice care and advance directives are reviewed for their effectiveness in reducing end-of-life costs, but these strategies are not promising at this time, largely because of the difficulty of predicting when an individual patient will die. It is suggested that curbing the rise in medical care costs will require basic changes in the physician-patient relationship and in our attitude to death. PMID- 7997220 TI - Making work more central to work disability policy. AB - The labor market trajectory of persons with and without disabilities is charted for the years 1981 through 1993. Data from the March Supplement to the Current Population Survey for these years show that changes in the labor market and in the specific work history of persons with disabilities are the main determinants both of their current employment situation and of whether they will lose or find jobs. Thus, the state of the overall labor market sets the basic parameters of employment among persons with disabilities, and then the specific work history of individuals determines whether they, among all persons with disabilities, will be working or will lose or find jobs. Public policy toward work disability must focus more on the impact both of trends in the labor market and of work history because these factors are crucial in determining the work outcomes of persons with disabilities. PMID- 7997221 TI - Psychiatric reimbursement reform in New York State: lessons in implementing change. AB - The failure of an innovative and ambitious reform in the psychiatric reimbursement system of New York State is examined for specific lessons of value for other states as they implement new payment strategies to encourage improved treatment of the mentally ill in general hospitals and community settings. The New York payment system was comprehensive, embracing both inpatient and outpatient care, and had significant support in the hospital and professional communities. Still, its impact on hospital performance was small and only partially consistent with its goals. For mental health reimbursement reform to succeed, state administrators must provide more clear, sustained, and forceful signals that take account of the real barriers to implementation; they must also ensure that the financial incentives and rewards are recognized by those who carry out the actions needed to translate goals into reality. PMID- 7997222 TI - Managing competition in public and private mental health agencies: implications for services and policy. AB - There were clear differences in our study between the management strategies employed by public agencies and those favored by private agencies. These differences, however, appeared to reflect the realities of financing rather than any fundamental differences in their orientation toward public service. There was no clear evidence that particular management practices affected an agency's performance on measures of financial access or acceptance of referrals from public hospitals. Government regulation and pressure from advocacy groups probably helped to maintain private agencies' focus on these and other public goals. From a public policy perspective, choosing a provider solely on the basis of ownership status is, at best, a naive approach to providing public mental health treatment. Not only is there great variation in process and practices within both private and public groups, but external factors such as competition from private practitioners may also exert a stronger influence on agency behavior than does ownership status. Because most current proposals for health care reform rely heavily on increased competition among providers to achieve their goals, the importance of ownership status as a predictor of conduct or performance may be further diminished. The emphasis on competition could increase differences between urban agencies and those in rural areas where there is less competition and, therefore, require different contracting approaches. As we move toward a health care system based on competition, administrators and policy makers will be forced to abandon their reliance on stereotypical public/private agency behavior as guides for policy decisions. Instead, they will have to consider more carefully the effects of political and market influences as well as agency characteristics when choosing community mental health providers. PMID- 7997223 TI - Redefining boundaries in the financing and care of diabetes: the Maryland experience. AB - The story of the development of the Maryland Medicaid Diabetes Care Program is narrated in this policy case study. Maryland Medicaid, a funding authority willing to assume a proactive role, decided to promote health care system changes expected to improve the health status of its recipients with diabetes. A state Medicaid budget crisis presented opportunities for financing new and expanded preventive services for those with this chronic disease. Specifically recounted is how Maryland Medicaid redefined its financing boundaries in an effort to overcome finance-induced fragmentation in diabetes health care delivery. The difficulties encountered by a single payer in moving unilaterally to alter health care practices are discussed. Two commentaries follow. PMID- 7997224 TI - Evaluation of new statewide health reform initiatives. PMID- 7997225 TI - Comments on the financing and care of diabetes. The impact of research on program success. PMID- 7997227 TI - A dilemma for medical education reform: form versus content. PMID- 7997226 TI - The prospect of sweeping reform in graduate medical education. PMID- 7997228 TI - Problems and promises: the potential impact of graduate medical education reform. PMID- 7997229 TI - A perspective from osteopathic medical schools. PMID- 7997230 TI - Cloning, expression, and alternative splicing of the receptor for anti-Mullerian hormone. AB - Anti-Mullerian hormone, also called Mullerian-inhibiting substance or factor, is a glycoprotein dimer belonging to the transforming growth factor-beta superfamily and synthesized by immature Sertoli cells and postnatal granulosa cells. Anti Mullerian hormone plays a key role in sex differentiation by inducing the regression of Mullerian ducts in the male fetus. It is also responsible for the stunting and masculinization of fetal ovaries in bovine freemartin fetuses and may be involved in the control of follicular maturation in the postnatal ovary. Using a degenerate probe for a consensus region of the transforming growth factor beta receptor superfamily to screen a complementary DNA library from rabbit fetal ovaries, we cloned a complementary DNA coding for a transmembrane serine/threonine kinase, which is expressed around the fetal Mullerian duct, in fetal and adult granulosa cells, and in immature Sertoli cells. Two transcripts, generated by alternative splicing of an exon coding for an N-terminal 61-amino acid domain, are strongly expressed in anti-Mullerian hormone target organs and Sertoli cells. The longer, 569-amino acid, isoform binds anti-Mullerian hormone when transiently expressed in COS cells and is believed to encode its functional receptor. PMID- 7997231 TI - Functional synergism between multiple thyroid hormone response elements regulates hepatic expression of the rat S14 gene. AB - Hepatic expression of the rat S14 gene is markedly and rapidly induced in response to T3. Previously, three contiguous restriction fragments of the S14 gene with thyroid hormone response activity were mapped to a region 2.5-3.0 kilobases upstream from the start of transcription [Far Upstream Regulatory region (FUR)]. To further investigate the molecular basis of the thyroid hormonal control of S14 gene expression, we have mapped the functional TRE sequences in the FUR region of the S14 gene. In vitro translated thyroid hormone receptor (TR) and retinoid X receptor were used in the gel retardation assays to map receptor binding sites in the S14 gene. Three TR-binding sequences were identified in the FUR region of the S14 gene and designated: FUR10 (from -2718 to -2694), FUR11 (from -2632 to -2595), and FUR12 (from -2582 to -2558). Each binding site contains two or more elements related to the consensus monomer binding motif 5' Pu-GGTCA. In FUR10 and FUR12, these motifs were arranged as direct repeats with 4 base pair spacing, while in FUR11 a more complex arrangement occurred. From mutagenesis experiments, all three TR-binding sequences in the S14 gene were found to play a role and synergize with each other in the responsiveness to T3. The importance of this functional synergy is also shown by the observations that at least two TR-binding sites are required for T3 induction in hepatocytes. In addition, synergy occurs between TR and additional regulatory sequences present in the FUR region and provides the maximal T3 response of the S14 gene. PMID- 7997232 TI - Thyroid-specific expression and cyclic adenosine 3',5'-monophosphate autoregulation of the thyrotropin receptor gene involves thyroid transcription factor-1. AB - The chimeric chloramphenicol acetyltransferase (CAT) construct, pTRCAT5'-199, containing the TSH receptor (TSHR) minimal promoter, -199 to -39 base pairs (bp), exhibits the thyroid specificity and TSH/cAMP autoregulation evident in TSHR gene expression. The present report shows that a cis-acting element between -189 and 175 bp, which binds thyroid transcription factor-1 (TTF-1), is involved in both activities. The 22 bp between -199 and -178 contains a positive element important for expression of the TSHR minimal promoter in rat FRTL-5 thyroid cells. DNAase I footprinting shows that extracts from functioning FRTL-5, but not non-functioning FRT thyroid or Buffalo rat liver (BRL) cells, protect a region between -189 and 175 bp. The protection is duplicated by TTF-1, and the protected element has only a two-base mismatch from the consensus TTF-1 element identified in the thyroglobulin (TG) and thyroid peroxidase minimal promoters. Gel mobility shift analyses reveal that FRTL-5 thyroid cell nuclear extracts form a specific protein/DNA complex with this region, which is prevented by the TTF-1 binding element from the TG promoter; FRT and BRL cell nuclear extracts do not have TTF-1 and do not form this complex. A role for the TSHR/TTF-1 binding element in thyroid-specific expression of the TSHR gene is evidenced as follows. Overexpression of TTF-1 in FRT or BRL cells, which have no TTF-1, increased the activity of pTRCAT5'-199, but not pTRCAT5'-177, which has no TTF-1 binding element. A nonsense mutation of the TTF-1 binding element eliminated TTF-1 induced activation of TSHR promoter activity in FRT or BRL cells and reduced TSHR promoter activity in FRTL-5 thyroid cells. In contrast, mutation of this element to the TTF-1 consensus sequence of the TG or thyroid peroxidase promoter had no significant influence on TSHR promoter activity. The activity of the TSHR/TTF-1 binding element requires a functioning cAMP response element (CRE). Thus, TTF-1 activity is lost when the CRE site is mutated to a nonfunctional, nonpalindromic sequence; it is, in contrast, maximized when CRE activity is maximized by its mutation to a consensus AP1 element. TTF-1 phosphorylation is important for binding and activity. Thus, binding of TTF-1 to the TSHR/TTF-1 element is phosphatase-sensitive and is increased by treating nuclear extracts with the catalytic subunit of protein kinase A. Overexpression of the catalytic subunit of PKA enhances TTF-1-increased activity of the TSHR minimal promoter.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 7997234 TI - Inhibition of rat prolactin (PRL) storage by coexpression of human PRL. AB - GH4C1 cells increase storage of rat PRL and accumulation of dense core secretory granules when they are treated with 300 nM insulin, 1 nM estradiol, and 10 nM epidermal growth factor. In the experiments reported here, intracellular rat PRL increased from 4% of the total amount produced in 24 h in control cultures to 15% in treated cultures. When GH4C1 cells were transfected with DNA sequences so that they coexpressed human PRL, the storage of rat PRL was no longer induced by hormone treatment; transfected clones contained less than 5% of the total produced in 24 h in both control and treated cultures. The sum of rat and human PRL produced by these clones was not more than rat PRL produced by the untransfected cells, so the storage capacity of the cells was not exceeded. The transfected clones made between 1 to 40 times more rat than human PRL. Release of human and rat PRL was stimulated by depolarizing the cells, indicating both still were in a regulated pathway, even though storage could not be induced. Mutations of human PRL with threonine substituted for asn31 or alanine substituted for ser34 did not block induction of rat PRL storage when coexpressed in GH4C1 clones. We conclude the ability to increase rat PRL storage is a process with marked specificity because it is inhibited by relatively low amounts of human PRL and inhibition requires asn31 and ser34 in human PRL. Such specificity is consistent with a receptor-mediated mechanism that concentrates PRL into dense cores of secretory granules. PMID- 7997233 TI - Secretion in AtT-20 cells stably transfected with soluble synaptotagmins. AB - Synaptotagmin (p65) is an integral membrane secretory vesicle-specific protein with two cytoplasmic repeats homologous to the C2 regulatory domain of protein kinase C. Synaptotagmin has been implicated in the regulation of neurotransmitter release from nerve growth factor-differentiated PC12 cells and from synapses in Drosophila, Caenorhabditis elegans, and squid. To address the function of synaptotagmin in endocrine cells, fragments of rat synaptotagmin I were stably expressed in the mouse anterior pituitary cell line AtT-20. The logic of these experiments is that the fragments may interfere with the endogenous synaptotagmin machinery, thus producing a dominant-negative phenotype. Transfected cells expressed the expected fragments that were comprised of either the first C2 repeat, the second C2 repeat, or the entire cytoplasmic domain. The fragments were localized to both soluble and membrane-associated cellular fractions, despite the absence of the transmembrane domain. The second C2 repeat was shown to coimmunoprecipitate with endogenous synaptotagmin, suggesting that protein protein interactions are mediating the membrane association of the fragments. These fragments had no effect on the targeting of regulated secretory vesicles or on regulated secretion as assayed by the release of ACTH and [3H]choline. Constitutive secretion assayed by the release of glycosaminoglycan side chains was also unaffected, as was the endocytic pathway monitored by the uptake and clearance of transferrin. These data suggest either the existence of a redundant pathway in secretion or that regulated membrane traffic in endocrine cells does not require synaptotagmin. PMID- 7997235 TI - Novel presence of luteinizing hormone/human chorionic gonadotropin (hCG) receptors and the down-regulating action of hCG on gonadotropin-releasing hormone gene expression in immortalized hypothalamic GT1-7 neurons. AB - We recently demonstrated that rat preoptic area and anterior hypothalamus, sites of GnRH neurons, contain receptors for LH/hCG. We investigated in the present study whether LH/hCG receptor and GnRH genes are coexpressed in the same neurons and whether LH/hCG can directly regulate GnRH gene expression in immortalized hypothalamic GT1-7 neurons. The immunostaining for both LH/hCG receptors and GnRH are present in the same neurons in rat preoptic area and the GT1-7 neurons. The reverse transcription-nested polymerase chain reaction generated an expected 255 basepair LH/hCG receptor fragment in GT1-7 neurons. Northern blotting showed the presence of a major 1.8-kilobase and minor 2.6- and 4.3-kilobase receptor transcripts. Immunoblotting detected an 80-kilodalton receptor protein. Covalent receptor cross-linking studies showed that [125I]hCG binds to an 80-kilodalton protein with a specificity expected of LH/hCG receptors. Scatchard plot analysis demonstrated that GT1-7 neurons contain a single class of high affinity (Kd = 3.8 x 10(-11) M) and low capacity (5000 sites/neuron) LH/hCG receptors. Culturing GT1 7 neurons with highly purified hCG resulted in a dose- and time-dependent decrease in steady state GnRH, but not glyceraldehyde-3-phosphate dehydrogenase, messenger RNA (mRNA) levels. Human and rat LH, but not hCG alpha or -beta, FSH, or TSH, mimicked the down-regulating action of hCG on GnRH mRNA levels. Pretreatment of GT1-7 neurons with LH/hCG receptor antisense, but not sense, phosphorothioate oligodeoxynucleotides for 48 h resulted in decreases in [125I]hCG binding and the GnRH mRNA response to exogenous hCG. The half-life of GnRH mRNA transcripts, as determined by blocking transcription by actinomycin-D, was 32.5 +/- 2.5 h. This half-life was virtually unchanged by treatment with 100 ng/ml hCG (30.5 +/- 3.5 h). Treatment of GT1-7 neurons with 100 ng/ml hCG resulted in a dramatic decrease in nuclear run-on transcription of GnRH, but not beta-actin, gene compared to that in the controls. The same hCG concentrations and time points that decreased steady state GnRH mRNA levels also decreased cellular GnRH protein levels. Paradoxically, hCG stimulated the secretion of preexisting GnRH until the levels were depleted. In summary, GnRH neurons in the rat preoptic area and GT1-7 neurons coexpress LH/hCG receptor gene. Treatment of GT1-7 neurons with LH/hCG results in a decrease in steady state GnRH mRNA levels. This decrease is dose and time dependent and hormone specific, and requires the presence of cellular LH/hCG receptors.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 7997236 TI - Cloning of complementary DNAs encoding the amphibian bombesin-like peptides Phe8 and Leu8 phyllolitorin from Phyllomedusa sauvagei: potential role of U to C RNA editing in generating neuropeptide diversity. AB - The bombesin-like peptides were originally characterized in frog skin, then later found to have a wide distribution and range of actions in mammals. The bombesin like peptides have classically been divided into three subfamilies, the bombesin subfamily, of which gastrin-releasing peptide (GRP) is the mammalian form; the ranatensin subfamily, of which neuromedin-B (NMB) is the mammalian form; and the phyllolitorin subfamily, which to date has only been characterized in amphibians. As a first step in characterizing mammalian phyllolitorin-like peptides, we have cloned complementary DNAs (cDNAs) encoding Leu8 and Phe8 phyllolitorin from Phyllomedusa sauvagei. Sequence analysis revealed that the amphibian phyllolitorin messenger RNA (mRNA) encodes a precursor of 90 amino acids containing a signal peptide sequence, an amino-terminal extension peptide, the phyllolitorin peptide of nine amino acids, and a carboxy-terminal extension peptide. Northern blot, reverse transcriptase-polymerase chain reaction (PCR), and in situ hybridization analysis showed that the mRNA was present at highest levels in skin, at lower levels in brain, and at lowest levels in gut. Phylogenetic analysis of bombesin-like peptide prohormone sequences showed that the phyllolitorin prohormones are much more closely related to the bombesin and ranatensin prohormones than to the GRP and NMB prohormones. This analysis suggests that the bombesin-like peptides should be reclassified into the GRP subfamily, the NMB subfamily, and the skin peptide subfamily. Surprisingly, the cDNAs encoding Phe8 and Leu8 phyllolitorins were identical except for a single T to C difference in the codon coding for the Phe or Leu residue of phyllolitorin.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7997237 TI - Identification of multiple, widely spaced estrogen-responsive regions in the rat progesterone receptor gene. AB - Progesterone receptors (PRs) mediate the actions of progestin hormones and play important roles during the reproductive cycle and pregnancy. Since PR expression is known to be regulated by estrogen, we have undertaken studies to examine the mechanisms underlying this regulation. We have identified multiple distinct regions of the rat PR gene, widely spaced and spread throughout the 5'-flanking region, the 5'-untranslated region, and the first exon (between -2264 and +2241), that can form a strong estrogen-responsive enhancer when linked together. Estrogen-responsive activities for two of the regions in isolation (+461/+636 and +2176/+2241) were demonstrated in one or more homologous or heterologous promoter contexts. The contributions of the other regions (-2264/-1970, -1167/-957 and +2088/+2110) to the overall activity of the assembled enhancer were cryptic in that they were only observed in the context of the other PR gene fragments, not in isolation. We identified four weak, but functional, imperfect estrogen response elements (EREs) in these regions of the PR gene, each differing from the consensus by 2 base pairs. In addition, we identified four ERE half-sites in the PR gene, three of which are paired (i.e. < 150 base pairs away) with the EREs in the estrogen-responsive regions. Competitive gel shift assays demonstrated weak, but detectable, binding of estrogen receptor to the EREs. Of note, the estrogen responsive enhancer assembled from the five regions of the PR gene exhibited promoter specificity; it conferred estrogen responsiveness of the distal PR gene promoter, but it failed to enhance the endogenous estrogen responsiveness of the proximal PR gene promoter. The positioning of response elements in the rat PR gene, which we show to be unique among steroid hormone-regulated genes, may have functional consequences for the regulation of the magnitude and timing of PR gene expression by estrogen. PMID- 7997238 TI - Genetic alteration of cyclic adenosine 3',5'-monophosphate-dependent protein kinase subunit expression affects calcium currents and beta-endorphin release in AtT-20 clonal pituitary cells. AB - The role of the cAMP-dependent kinase (AK) in neurotransmission was investigated by genetic alteration of AK subunit expression in AtT-20 clonal pituitary cells. We characterized and compared wild-type [AK(wt)] cells and two clones with different AK activities. The first stably expresses a gene for a mutant AK regulatory subunit (RI) that does not bind cAMP [AK(-)]; the second stably expresses a gene for the catalytic subunit (C) of AK [AK(+)]. Western blot analysis of RI and C subunit expression showed increased expression of both subunits in AK(+) and AK(-) cells relative to AK(wt), with the transfection induced expression of one subunit producing a compensatory increase in the expression of the other. The basal AK activities varied among the cell types, with AK(+) cells possessing 3-fold higher basal AK activity than AK(wt) cells, and AK(-) cells possessing half the AK activity of AK(wt) cells. Preincubation of cultures with 300 microM 8-(4-chlorophenylthio)-cAMP increased AK activity approximately 4-fold in AK(wt) and AK(+) cells, but was without effect in AK(-) cells. Subsequent addition of 1 microM cAMP in vitro increased AK activity an additional 2- to 3-fold in all cell types. The higher basal AK activity found in AK(wt) and AK(+) cells was associated with larger whole cell calcium currents (approximately 43% and approximately 75% larger than in AK(-) cells, respectively) and faster rates of current rundown. The currents from each cell line had similar voltage-dependent and pharmacological properties, however, and [3H]PN200-110 binding was similar among the cell types. Maximal currents were evoked at clamp potentials of 0-10 mV; currents were inactivated approximately 30% in the steady state at holding potentials of -40 mV compared to -80 mV, and currents were reduced approximately 45% in the presence of nifedipine at -40 mV, but were insensitive to omega-conotoxin GVIA. AK(wt) and AK(+) cells also had higher basal and cAMP-stimulated release of beta-endorphin; control rates were approximately 50% greater, but stimulated rates were approximately 400% greater compared to those in AK(-) cells. We conclude that a greater number of calcium channels were activated by depolarization in the phosphorylated state, that current rundown was largely due to dephosphorylation, and that activation of calcium channels was coupled to the release of beta-endorphin.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 7997239 TI - Characterization of gonadal sex cord-stromal tumor cell lines from inhibin-alpha and p53-deficient mice: the role of activin as an autocrine growth factor. AB - Inhibin-alpha-deficient mutant mice have been generated by a targeted deletion of the inhibin-alpha gene through homologous recombination in murine embryonic stem cells. Essentially all of the homozygous mutants develop gonadal sex cord-stromal tumors. To investigate their endocrine and proliferative characteristics, gonadal tumor cells were maintained in vitro. Cells from inhibin-alpha-deficient mice multiplied poorly; however, cells from mice deficient in both inhibin-alpha and p53 proliferated rapidly and showed higher saturation density and plating efficiency, thus allowing the establishment of clonal tumor cell lines. Although negligible estrogen and testosterone was produced by the clonal cells, high levels of progesterone were secreted. A clonal testis tumor cell line (inhibin alpha/p53 deficient) showed no response to exogenous FSH, human CG (hCG), or inhibin A but exhibited a 6- to 8-fold increase in progesterone production in response to forskolin treatment. The stimulatory effect of forskolin was, however, partially blocked by activin treatment. Northern blot analysis revealed inhibin beta A and beta B mRNA expression in these cells. Furthermore, Western blot analyses indicated the secretion of the beta A-subunit protein. We further tested the role of activin on tumor cell growth. Treatment with follistatin, an activin-binding protein, inhibited tumor cell replication in a dose-dependent manner. In contrast, treatment with activin A stimulated tumor cell growth by itself and partially blocked follistatin action. Incorporation of thymidine into DNA of these cells was also stimulated by activin. In addition, treatment with antiactivin A serum inhibited tumor cell replication and blocked the stimulatory action of activin on cell growth. The activin action is likely mediated by specific receptors because cross-linking of [125]activin to the 50-55 kilodalton type I and 75-80 kilodalton type II receptors was found using sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis. Northern blot analysis also revealed follistatin mRNA expression in the tumor cells, suggesting these cells are related to granulosa cells. Our findings indicate that activin can act as an autocrine growth factor in stimulating the proliferation of gonadal tumor cell lines derived from inhibin-alpha and p53-deficient mice and inhibits progesterone production. These tumor cell lines are useful for studies on the regulation of gonadal cell proliferation and steroidogenesis as well as the signaling pathway mediating activin action. PMID- 7997240 TI - A new orphan member of the nuclear hormone receptor superfamily closely related to Rev-Erb. AB - We have isolated complementary DNA clones encoding a novel orphan member of the nuclear receptor superfamily, termed BD73. This protein shows strong amino acid sequence similarity to the previously described Rev-ErbA alpha. Unlike Rev-Erb, in which the opposite strand of the C-terminal coding region encodes the C terminal portion of a variant thyroid hormone receptor isoform, the opposite strand of the C-terminal coding region of BD73 does not have any extensive open reading frames. BD73 messenger RNA is expressed in a wide variety of tissues and cell lines. In quiescent HepG2 cells, BD73 messenger RNA levels are strongly induced by planar aromatic antioxidants. Like Rev-Erb, BD73 binds as a monomer to a DNA sequence which consists of a specific A/T-rich sequence upstream of the consensus hexameric half-site specified by the P box of the DNA-binding domain. Amino acid sequence comparisons suggest that the A box sequence, which has been suggested to mediate monomer binding by other superfamily members, lies closer to the DNA-binding domain in BD73 and Rev-Erb than in other receptors. Under the conditions examined, neither BD73 nor Rev-Erb activated reporters containing multiple copies of their common binding site. Thus, these two orphans may require an as yet unidentified ligand or other signal for such activation. Together, BD73 and Rev-Erb define a subgroup of orphan receptors that bind as monomers to a half site flanked by a specific and extended A/T-rich sequence. PMID- 7997241 TI - Induction of hyperphosphorylation and activation of the p56lck protein tyrosine kinase by phenylarsine oxide, a phosphotyrosine phosphatase inhibitor. AB - The T cell protein tyrosine kinase p56lck is implicated in thymic development and mitogenic activation of T lymphocytes, and is itself regulated by reversible tyrosine phosphorylation. When phenylarsine oxide (PAO), a membrane-permeable inhibitor of phosphotyrosine phosphatases, was added to Jurkat T leukemia or LSTRA thymoma cells, the phosphate content of p56lck increased rapidly. The sites of increased phosphorylation were mapped to Tyr-192, Tyr-394 and Tyr-505. Hyperphosphorylated p56lck displayed retarded mobility on SDS gels, unaltered or marginally increased cytoskeletal association, and its catalytic activity changed in a biphasic manner; during the first 10-20 min of PAO-treatment the activity increased and then it declined to very low values within 1-2 hr. Our data suggest that p56lck contains both positive and negative regulatory sites which are constantly dephosphorylated at an unexpectedly high rate by cellular phosphotyrosine phosphatases. PMID- 7997242 TI - Effects of MHC II conformation and pH on the recognition of peptide by T cells. AB - In this study we analysed the binding of the peptide HEL46-61 to purified Ak molecules which have been altered by site-directed mutagenesis at polymorphic positions to include amino acids from the Ad alpha-chain. We find that changes in the floor of the peptide binding groove, at positions 11, 14 and 28, abolish T cell recognition without changing peptide binding affinity. We further show that amino acid changes at these positions in the Ad molecule result in a conformationally altered molecule as evidenced by loss of binding of the Ad alpha specific monoclonal antibody K24. Thus the T cell receptor is highly sensitive to subtle changes in MHC II structure induced at sites that are unlikely to be involved in direct T cell contact. This has important implications with respect to allorecognition. The binding studies reported here were performed both at pH 7, to reflect binding of peptides at the cell surface, and at pH 5.5, to mimic binding in an intracellular acidic compartment. Binding to wild-type Ak was increased 2-3-fold at pH 5.5, whereas binding to some MHC II mutants was increased by greater than 20-fold at pH 5.5 relative to pH 7. These results show that the apparent peptide binding specificity for the mutants differs at pH 7 and 5.5, and suggest that caution should be used in defining the MHC-restriction of peptide epitopes at neutral pH. PMID- 7997243 TI - Dimeric recombinant IgA directed against carcino-embryonic antigen, a novel tool for carcinoma localization. AB - Carcinoembryonic antigen (CEA) has been shown to be one of the best markers for in vivo tumor targeting of radiolabeled antibodies, despite the fact that it is localized predominantly at the apical side of human colon carcinoma cells within the fairly closed pseudolumen structures formed by these tumors. Due to this particular histological localization, a large proportion of the CEA molecules may remain inaccessible to the intravenously injected radiolabeled anti-CEA antibodies of IgG isotype, which are widely used in the clinic. In order to improve targeting, we made a recombinant dimeric IgA, which should have the capacity to translocate from the basolateral to the apical side of the pseudolumen formed by colon carcinoma cells after binding to the polyIg receptor (pIgR). A genomic chimeric mouse-human IgA2 construct was made using one of our most specific anti-CEA hybridomas, CE-25. The chimeric IgA (chIgA) was expressed in the Sp2/0 myeloma cell line. The secreted recombinant antibody was found to consist mostly of a dimeric form of IgA with a molecular weight of about 350 kDa. The dimeric chIgA was shown to translocate efficiently in vitro across a monolayer of epithelial cells expressing the pIgR and to retain full CEA binding activity. PMID- 7997244 TI - C3b covalently associated to tetanus toxin modulates TT processing and presentation by U937 cells. AB - Complement protein C3, like C4 and alpha 2-macroglobulin (alpha 2M), is a potentially bivalent ligand: (1) its proteolytic fragment, C3b, is able to interact covalently with antigens, and (2) this bound fragment is able to interact non-covalently with specific complement receptors of antigen presenting cells (APC). The formation of antigen-C3b complexes frequently occurs in vivo at inflammatory sites during the early stages of an immune response. Tetanus toxin (TT)-C3b covalent complexes, prepared from purified proteins, were used to study how C3b association influences the handling of TT by U937 cells used as APC. TT specific T cell proliferation following TT-C3b processing was observed at a concentration when TT alone was inefficient. Whereas TT pinocytic uptake was low, TT-C3b uptake, through the help of complement receptor CR1, was three times higher. Free TT was rapidly transported to the lysosomes where it was proteolysed, whereas TT-C3b complexes were first retained in the endosomes and underwent only limited proteolysis. While the ester link of the complexes was fairly stable in the endosomes, it was gradually hydrolysed in the lysosomes with ensuing efficient proteolysis of the two proteins. This reflects the fact that associated C3b escorts TT during intracellular trafficking in the APC, and influences antigen processing. A triple role of C3b escorting antigen residues at the level of antigen uptake, routing, and proteolysis inside U937 cells, thus modulating antigen-dependent T cell proliferation. PMID- 7997245 TI - Generation of soluble interleukin-1 receptor from an immunoadhesin by specific cleavage. AB - The extracellular portion of the interleukin-1 receptor (IL-1R) is sufficient for high-affinity binding to IL-1; however, the structural basis for binding of the receptor to IL-1 is not known. To produce individual domains of IL-1 receptor for structural studies, we constructed a molecular fusion of IL-1 receptor with immunoglobulin G heavy chain that contains a protease specific sequence joining the two portions of the molecule (IL-1R-G-IgG). We introduced the hexapeptide sequence AAHY:TL (where ":" denotes the scissile bond) at the junction of the IL 1R and IgG regions, for specific cleavage by an H64A variant of subtilisin BPN' (Genenase I), an endoprotease that cleaves selectively at this sequence (Carter et al., (1989) Proteins 6, 240-248). Plasmid DNA encoding the fusion protein was used to transfect human embryonic kidney 293 cells transiently, and secreted IL 1R-G-IgG was purified from cell supernatants by protein A chromatography. The IL 1 receptor's extracellular region was then generated by enzymatic cleavage with Genenase I which was immobilized on controlled-pore glass. Incubation of IL-1R-G IgG with immobilized Genenase I resulted in specific cleavage at the target site, as confirmed by SDS-PAGE, immunoblotting and direct sequencing of the newly generated termini. The resulting soluble IL-1R was separated from the immunoglobulin Fc cleavage product by re-chromatography on protein A. The purified, soluble IL-1R retained quantitatively the ability to bind to its ligand, IL-1 beta. This approach offers a generic means by which the extracellular region of a given type I transmembrane receptor can be expressed as an immunoadhesin, released enzymatically and then easily purified for crystallographic or ligand binding studies. PMID- 7997246 TI - Molecular and biological properties of an interleukin-1 receptor immunoadhesin. AB - Overproduction of the cytokine interleukin 1 (IL-1) is an important factor in the pathogenesis of several autoimmune and inflammatory disease. To develop a recombinant inhibitor of IL-1 with an extended pharmacologic half-life, we constructed an IL-1 receptor immunoadhesin (IL-1R-IgG), by fusing the extracellular domain of the type IL-1 receptor with the hinge and Fc regions of human IgG1 heavy chain. Transfected human 293 cells express IL-1R-IgG as a secreted, disulfide-bonded homodimer. The secreted protein contains an intact antibody Fc region, as indicated by immunoblotting, and a functional IL-1 receptor region, as indicated by ligand-blotting. Saturation binding analysis indicates an equilibrium dissociation constant (KD) of 350 pM for the binding of IL-1R-IgG to its ligand, IL-1 beta. Kinetic analysis of the binding reveals an off rate of 0.1 min-1 and an on rate of 1.5 x 10(8) min-1 M-1, yielding a calculated KD of 770 pM. These binding properties are similar to those of cell surface type I IL-1 receptor. IL-1R-IgG is capable of inhibiting the biological activity of IL-1 beta in vitro, as evidenced in a thymocyte proliferation assay. Pharmacokinetic analysis in mice indicates that IL-1R-IgG has a terminal half life of 91 hr in the blood circulation. This half-life is markedly longer than the values reported for other recombinant inhibitors of IL-1 such as the IL-1 receptor antagonist or soluble IL-1 receptor. Thus, IL-1R-IgG may be useful for investigating the interaction of IL-1 with its receptor and the role of IL-1 in disease, as well as for potential intervention in pathological situations involving overproduction of IL-1. PMID- 7997247 TI - Antigenicity and immunogenicity of P30-derived peptides in experimental models of toxoplasmosis. AB - P30, also referred to as SAG-1, is now recognized as a major Toxoplasma gondii antigen potentially important for both diagnosis and immunoprophylaxis of toxoplasmosis. By using predictive algorithms, five synthetic peptides (48-67, 82 102, 213-230, 238-256 and 279-285) derived from P30, were investigated for B- and T-cell determinants in mouse and rat experimental models. Antibody recognition appeared more broadly distributed along the P30 sequence, whereas T-cell recognition was mainly targeted on the 238-256 peptide. In the absence of any carrier protein, this peptide induced a B- and T-cell immune response independent of the route of immunization (oral route or subcutaneous injection). This peptide (238-256) induced multiple antibody isotypes. In contrast with the 238-256 peptide, the 48-67 peptide, either free or in the form of a multiple antigenic peptide (MAP) construct or the 279-295 peptide, elicited antibodies associated with a TH2 response. This study reports for the first time the analysis of the antigenic and immunogenic properties of P30-derived peptides and are potentially useful for vaccinal strategies incorporating the P30 Toxoplasma gondii antigen. PMID- 7997248 TI - Retinoblastoma protein regulation of surface CD74 (invariant chain) expression in breast carcinoma cells. AB - The HLA class II genes encode heterodimeric cell surface proteins which bind peptide antigen recognized by T-cell receptors on CD4+ T-cells. The class II proteins are inducible by IFN-gamma, and this induction requires, or is strongly enhanced, by retinoblastoma protein (RB) in a series of breast carcinoma cell lines. Loading of peptide onto the class II protein appears to be regulated by CD74, which associates with class II during their transition to the endosomal compartment, where class II binds peptide. Class II proteins and CD74 are largely regulated in concert, provoking the question, is CD74 induction by IFN-gamma affected by RB? Results described here indicate that IFN-gamma induction of CD74 surface expression in a series of breast carcinoma lines is enhanced by RB, while RB has no effect on CD74 mRNA induction. Also, neither the class II nor the CD74 promoter regions are activated by RB in cotransfection experiments where RB activates the SV40 promoter. PMID- 7997249 TI - Sequences of heavy and light chain variable regions from four bovine immunoglobulins. AB - Oligodeoxyribonucleotide primers based on the 5' ends of bovine IgG1/2 and lambda constant (C) region genes, together with primers encoding conserved amino acids at the N-terminus of mature variable (V) regions from other species, have been used in cDNA and polymerase chain reactions (PCRs) to amplify heavy and light chain V region cDNA from bovine heterohybridomas. The amino acid sequences of VH and V lambda from four bovine immunoglobulins of different specificities are presented. PMID- 7997250 TI - Molecular cloning of feline interleukin 12 p35 reveals the conservation of leucine-zipper motifs present in human and murine IL-12 p35. PMID- 7997252 TI - Science in Central Europe. PMID- 7997251 TI - The nature and processes of preverbal learning: implications from nine-month-old infants' discrimination problem solving. AB - Nine-month-old infants' performance on discrimination-learning problems was investigated in four experiments using the synchronous reinforcement paradigm. These experiments were organized around basic theoretical postulates concerning the relation between attention and learning. In each of the experiments, infants were trained to respond differentially to a particular stimulus feature, with the goal of establishing whether they could learn to respond to a particular stimulus feature under conditions where other stimulus dimensions were present and varying. In the first experiment, 48 infants were trained to fixate visually on a particular feature in a pair of stimuli that varied in color, form, and position dimensions. Contingencies for responding were then shifted either within a dimension (reversal shift) or across dimensions (nonreversal shift). Infants learned to respond to the reinforced feature during initial training; moreover, infants assigned to a reversal shift condition showed a higher level of transfer of learning during the test phase than those assigned to a nonreversal shift condition. The second experiment extended the results of Experiment 1 by testing 48 additional infants under conditions in which the number of varying irrelevant dimensions was increased during the shift phase. Although the difficulty added to this task by this manipulation made transfer more difficult for all infants, results again indicated that transfer of learning was more evident for infants in a reversal shift than a nonreversal shift condition. In the third experiment, 64 infants were trained in a similar manner, except that completely new values were substituted during shift phases on the color and form dimensions. This manipulation was meant to probe whether infants were formulating a dimension response from previous training and to test the predictions of such dimension processing for transfer of learning to a functionally new problem. Infants were reinforced for fixating on a new feature either within the same dimension as during training (intradimension shift) or within the dimension that was not originally trained (extradimension shift). Transfer of learning was clearly superior in the intradimension shift condition. The findings of the first three experiments suggested that, during discrimination-learning problems, infants selected and tested individual stimulus features and dimensions from an array of potential solutions to the problem until discovering the one that was consistently associated with reinforcement.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 7997253 TI - Promega files court challenge to Roche's Taq enzyme patent. PMID- 7997254 TI - Call for risk/benefit study of gene therapy. PMID- 7997255 TI - Italy drops decision to quit EMBL. PMID- 7997256 TI - Signal transduction. Look at a tyrosine kinase. PMID- 7997257 TI - Cancer. Sun protection factor p53. PMID- 7997258 TI - Regulation of BRCA1. PMID- 7997259 TI - Mind control. PMID- 7997260 TI - Visceral leishmaniasis and AIDS. PMID- 7997261 TI - A protein kinase involved in the regulation of inflammatory cytokine biosynthesis. AB - Production of interleukin-1 and tumour necrosis factor from stimulated human monocytes is inhibited by a new series of pyridinyl-imidazole compounds. Using radiolabelled and radio-photoaffinity-labelled chemical probes, the target of these compounds was identified as a pair of closely related mitogen-activated protein kinase homologues, termed CSBPs. Binding of the pyridinyl-imidazole compounds inhibited CSBP kinase activity and could be directly correlated with their ability to inhibit cytokine production, suggesting that the CSBPs are critical for cytokine production. PMID- 7997262 TI - Crystal structure of the tyrosine kinase domain of the human insulin receptor. AB - The X-ray crystal structure of the tyrosine kinase domain of the human insulin receptor has been determined by multiwavelength anomalous diffraction phasing and refined to 2.1 A resolution. The structure reveals the determinants of substrate preference for tyrosine rather than serine or threonine and a novel autoinhibition mechanism whereby one of the tyrosines that is autophosphorylated in response to insulin, Tyr 1,162, is bound in the active site. PMID- 7997263 TI - Sunburn and p53 in the onset of skin cancer. AB - Squamous cell carcinoma of the skin (SCC) can progress by stages: sun-damaged epidermis, with individual disordered keratinocytes; actinic keratosis (AK), spontaneously regressing keratinized patches having aberrant cell differentiation and proliferation; carcinoma in situ; SCC and metastasis. To understand how sunlight acts as a carcinogen, we determined the stage at which sunlight mutates the p53 tumour-suppressor gene and identified a function for p53 in skin. The p53 mutations induced by ultraviolet radiation and found in > 90% of human SCCs were present in AKs. Inactivating p53 in mouse skin reduced the appearance of sunburn cells, apoptotic keratinocytes generated by overexposure to ultraviolet. Skin thus appears to possess a p53-dependent 'guardian-of-the-tissue' response to DNA damage which aborts precancerous cells. If this response is reduced in a single cell by a prior p53 mutation, sunburn can select for clonal expansion of the p53 mutated cell into the AK. Sunlight can act twice: as tumour initiator and tumour promoter. PMID- 7997264 TI - Hippocampal long-term potentiation and neural cell adhesion molecules L1 and NCAM. AB - Synaptic membranes express cell adhesion molecules. Here we investigate the role of the neural cell adhesion molecules L1 and NCAM in hippocampal long-term potentiation (LTP), a sustained-use-dependent increase in synaptic efficacy that has been implicated in learning and memory. L1 and NCAM mediate cell interactions during neural development and are strongly expressed in the hippocampus. They cooperate to strengthen L1-dependent cell adhesion and are coupled to second messenger pathways. We show that LTP in CA1 neurons of rat hippocampal slices was reduced by application of various L1 and NCAM antibodies, recombinant L1 fragments, and upon dissociation of the L1/NCAM complex through oligomannosidic carbohydrates and NCAM peptides. Neither the activation of NMDA (N-methyl-D aspartate) receptors nor the maintenance of LTP was affected. These results suggest that L1 and NCAM modulate the development or the stabilization of LTP. PMID- 7997265 TI - Control of type-D GABAergic neuron differentiation by C. elegans UNC-30 homeodomain protein. AB - The Caenorhabditis elegans gene unc-30 is required for the development and functioning of the 19 inhibitory GABAergic (gamma-aminobutyric-acid-secreting) type D motor neurons, which control locomotion. In unc-30 mutants the D neurons lack GABA and have defects in axonal pathfinding and synaptic connections (J. White, personal communication). We report here that unc-30 encodes a homeodomain protein that is present in the nuclei of the D neurons at high levels in young larvae, in which the motor circuitry is formed, and at low levels in older animals. The UNC-30 protein is also present in six non-GABAergic neurons and is absent from the seven non-D-type GABAergic neurons. Ectopic expression of unc-30 induced GABA expression in cells that are normally not GABAergic. We propose that unc-30 functions as a transcriptional regulator within the type D neurons to control their terminal differentiation and that unc-30 is sufficient in some but not all cell types to induce GABA expression. PMID- 7997266 TI - dpp induces mesodermal gene expression in Drosophila. AB - Inductive interactions between germ layers are an essential feature of the development of many organisms. In several species these interactions are mediated by members of the transforming growth factor-beta (TGF beta) family. In amphibians, different concentrations of activin can induce different types of mesoderm in the animal cap assay. In Drosophila, a member of the TGF beta family, decapentaplegic (dpp), acts as an inductive signal. Midway through embryogenesis, dpp is expressed in the visceral mesoderm, and enhances the expression of the homeotic gene labial in the underlying midgut endoderm. Earlier in development, however, dpp expression is limited to the dorsal ectoderm. At this stage in development, thickveins, a dpp receptor, is expressed in the mesoderm, and this suggests that ectodermal dpp might not only be required for development of dorsal ectoderm, but could also act inductively to mediate pattern formation in the underlying mesoderm. Here we show, by expressing dpp ectopically in the ectoderm and mesoderm and by examining dpp null mutant embryos, that dpp regulates expression of mesodermal genes. PMID- 7997267 TI - Integrin-mediated signal transduction linked to Ras pathway by GRB2 binding to focal adhesion kinase. AB - The cytoplasmic focal adhesion protein-tyrosine kinase (FAK) localizes with surface integrin receptors at sites where cells attach to the extracellular matrix. Increased FAK tyrosine phosphorylation occurs upon integrin engagement with fibronectin. Here we show that adhesion of murine NIH3T3 fibroblasts to fibronectin promotes SH2-domain-mediated association of the GRB2 adaptor protein and the c-Src protein-tyrosine kinase (PTK) with FAK in vivo, and also results in activation of mitogen-activated protein kinase (MAPK). In v-Src-transformed NIH3T3, the association of v-Src, GRB2 and Sos with FAK is independent of cell adhesion to fibronectin. The GRB2 SH2 domain binds directly to tyrosine phosphorylated FAK. Mutation of tyrosine residue 925 of FAK (YENV motif) to phenylalanine blocks GRB2 SH2-domain binding to FAK in vitro. Our results show that fibronectin binding to integrins on NIH3T3 fibroblasts promotes c-Src and FAK association and formation of an integrin-activated signalling complex. Phosphorylation of FAK at Tyr 925 upon fibronectin stimulation creates an SH2 binding site for GRB2 which may link integrin engagement to the activation of the Ras/MAPK signal transduction pathway. PMID- 7997268 TI - Heterogeneity of channel density in inositol-1,4,5-trisphosphate-sensitive Ca2+ stores. AB - Inositol-1,4,5-trisphosphate (InsP3)-induced Ca2+ release is a key mechanism for intracellular Ca2+ mobilization. The rate of Ca2+ release declines progressively with time until a higher concentration of InsP3 is added, which is referred to as the incremental detection mechanism. Two hypotheses have been postulated to explain these complex kinetics: (1) Ca2+ stores consist of multiple compartments (quanta) with different sensitivities to InsP3 (refs 3-7), and (2) the rate of Ca2+ release is modulated by the Ca2+ concentration in the lumen of Ca2+ stores. We studied this phenomenon by real-time measurement of the luminal Ca2+ concentration of Ca2+ stores using a Ca(2+)-sensitive fluorescent dye, but our results were not explained by either of these hypotheses. Here we report that the complex kinetics of Ca2+ release results from the heterogeneous density of equally InsP3-sensitive channels on the Ca2+ stores. This heterogeneity creates Ca2+ stores with apparently different sensitivities to InsP3, which may have different functions in Ca2+ mobilization. PMID- 7997269 TI - Role of SAPK/ERK kinase-1 in the stress-activated pathway regulating transcription factor c-Jun. AB - The stress-activated protein kinases (SAPKs), which are distantly related to the MAP kinases, are the dominant c-Jun amino-terminal protein kinases activated in response to a variety of cellular stresses, including treatment with tumour necrosis factor-alpha and interleukin-beta (refs 1, 2). SAPK phosphorylation of c Jun probably activates the c-Jun transactivation function. SAPKs are part of a signal transduction cascade related to, but distinct from, the MAPK pathway. We have now identified a novel protein kinase, called SAPK/ERK kinase-1 (SEK1), which is structurally related to the MAP kinase kinases (MEKs). SEK1 is a potent activator of the SAPKs in vitro and in vivo. An inactive SEK1 mutant blocks SAPK activation by extracellular stimuli without interfering with the MAPK pathway. Although alternative mechanisms of SAPK activation may exist, as an immediate upstream activator of the SAPKs, SEK1 further defines a signalling cascade that couples cellular stress agonists to the c-Jun transcription factor. PMID- 7997270 TI - Activation of stress-activated protein kinase by MEKK1 phosphorylation of its activator SEK1. AB - A kinase distinct from the MEK activator Raf, termed MEK kinase-1 (MEKK), was originally identified by virtue of its homology to kinases involved in yeast mating signal cascades. Like Raf, MEKK is capable of activating MEK in vitro. High-level expression of MEKK in COS-7 cells or using vaccinia virus vectors also activates MEK and MAPK, indicating that MEKK and Raf provide alternative means of activating the MAPK signalling pathway. We have derived NIH3T3 cell sublines that can be induced to express active MEKK. Here we show that induction of MEKK does not result in the activation of MAPK, but instead stimulates the stress-activated protein kinases (SAPKs) which are identical to a Jun amino-terminal kinase. We find that MEKK regulates a new signalling cascade by phosphorylating an SAPK activator, SEK1 which in turn phosphorylates and activates SAPK. PMID- 7997271 TI - Involvement of microtubule motors in basolateral and apical transport in kidney cells. AB - The maintenance of a polarized cell surface requires vectorial transport of vesicles to the apical and the basolateral membrane domains. Transport of newly synthesized apical proteins and trans-cytosis from the basolateral to the apical surface have been demonstrated to depend on microtubules. In contrast, movement of membrane proteins to the basolateral surface has been claimed to occur by diffusion and to be microtubule- and actin-independent. We have re-examined the role of microtubules using a recently developed polarized transport assay in permeabilized Madin-Darby canine kidney cells. Here we report that both apical and basolateral transport is inhibited by nocodazole treatment. Transport to the basolateral surface was inhibited by immunodepletion of cytosolic kinesin. In contrast, apical transport involved both dynein and kinesin. Our data demonstrate that in epithelial cells, microtubule motors are involved in the movement of apical and basolateral vesicles. Moreover, we propose that the differential requirement for microtubule-based motors is related to the microtubule organization. PMID- 7997272 TI - XL alpha s is a new type of G protein. AB - The GTP-binding proteins are well-known regulators of cellular functions, including vesicular transport. Cholera toxin, which is known to catalyse ADP ribosylation of the alpha s subunit of heterotrimeric G proteins, stimulates secretory vesicle formation from the trans-Golgi network. Here we describe a new cholera toxin target, an 'extra large' G protein (XL alpha s; M(r) 92K) which consists of a new 51K XL-portion linked to a G alpha s truncated at the amino terminus. XL alpha s is specifically associated with the trans-Golgi network and occurs selectively in cells containing both the regulated and the constitutive pathway of protein secretion. Hence, XL alpha s may mediate the effects of cholera toxin on secretory vesicle formation. PMID- 7997273 TI - Localization of pre-mRNA splicing in mammalian nuclei. AB - In mammalian nuclei, precursor messenger RNA splicing factors are distributed non uniformly. Antibodies directed against structural polypeptides of small nuclear ribonucleoprotein particles (snRNPs) and some non-snRNP splicing factors have shown that these components are concentrated in about 20-50 nuclear 'speckles'. These and other non-homogeneous distributions have been proposed to indicate nuclear 'compartments' that are distinct from the sites of transcription and in which RNA processing occurs. We have tested this idea using a new approach. Previous structural and biochemical data have shown that splicing can occur in association with transcription. Nascent RNA of specific genes can be detected by in situ hybridization as intense spots of nuclear stain which map to the sites of transcription. Here we identify active pre-mRNA splicing sites by localizing the nascent spliced mRNA of specific genes. We find that splicing occurs at the sites of transcription, which are not coincident with intranuclear speckles. We conclude that the nucleus is not compartmentalized with respect to transcription and pre-mRNA splicing. PMID- 7997274 TI - Patents in the public interest. AB - The UK High Court has granted an injunction allowing Chiron Corporation a monopoly in selling hepatitis C virus test kits. The decision will be welcomed by the pharmaceutical and biotechnology industries. PMID- 7997275 TI - Nurses vs. doctors: the battle between the caregivers in health care reform. PMID- 7997276 TI - Facing the substance abuse problem. PMID- 7997277 TI - King's theory as a framework for quality: linking theory to practice. AB - Quality care has long been an elusive concept. The pushing of health care services into community settings by health care reform demands new attention to the concept of quality. King's theory of goal attainment can provide a framework for the definition and delivery of quality care in community-based health services. PMID- 7997278 TI - Fetal well-being I: The health care provider's responsibility in the first trimester. PMID- 7997279 TI - Steps to successful visits with elected officials. AB - Holding successful and productive meetings with elected officials and bureaucrats requires preparation and experience. This article outlines steps to take before, during, and after a meeting with policymakers, to maximize the impact of these contacts. PMID- 7997280 TI - Nursing's role in health policy research. PMID- 7997281 TI - A collaborative community model for nursing research: meeting the agenda for the 90's. AB - Nursing research can be fostered in an era of constrained resources through the collaborative efforts of university faculty and community agencies. A model for establishing a formal structure linking doctorally-prepared nursing faculty with nurses in eight clinical agencies is described. The model provides affiliative status, maximizes the utilization of human and material resources, and affords conduct of both individual and multiple-site research programs. PMID- 7997282 TI - Educational outreach in a rural underserved area. AB - A school of nursing in a world-renowned urban medical center joined forces with a school of nursing in a rural, underserved, ethnic minority area 350 miles distant. By working together, the two schools of nursing re-energized professional nursing in a geographically remote area of Texas. This underserved region is the fastest growing area in the state; education and health care resources have not kept pace with demand. Consequently, nursing faculty recruitment lagged, two few nurses had advanced practice skills, and morale suffered because of nursing staff and faculty shortages. Leadership in the two schools forged an educational and political partnership to create a collaborative model to meet the higher education needs of this area of southwest Texas. By detailing the eight steps of a unique success story, the article offers a model for meeting the evolving health care and nursing education needs of the '90's. PMID- 7997283 TI - The ethics of cultural diversity and culturally competent nursing education, practice, and research. PMID- 7997284 TI - Partners in clinical teaching. AB - This article describes the importance of preparing the clinical environment to facilitate clinical instruction of undergraduate nursing students. Clinical competence of the faculty member, respect for the judgement and skills of nursing staff and the expectation that students, faculty and staff collaborate to enhance quality patient care all are important in developing positive learning experiences for students. PMID- 7997285 TI - What's a nice nurse like you doing in an information system like this? PMID- 7997286 TI - The art of nursing: what's new is old. PMID- 7997287 TI - Professionalism in the '90s. PMID- 7997288 TI - A public awareness campaign as a celebration during nurses week. AB - As advanced practice nurses take a more significant role in health care reform, efforts may be needed to educate the public about their advanced nursing skills, knowledge, and expertise. A television public awareness campaign featuring advanced practice nurses can be used to highlight such expertise and knowledge. A Wisconsin district nurses association coordinated a television campaign consisting of seven, 1-minute television spots to air on the evening news during Nurses Week in 1994. Each spot focused on an advanced practice nurse and his or her clinical practice. PMID- 7997289 TI - Health reform: "a little bit at a time". PMID- 7997290 TI - Creative alliances between nursing service and education in times of economic constraint. AB - Health care and higher education in America are both in economic crisis and undergoing reform. Forming collaborative relationships between health care providers and nursing educational institutions is a savvy, economical, and mutually beneficial strategy in these changing times. Creative alliances between service and education are addressed in terms of clinical educational preceptorships for senior nursing students and joint appointments between service and education. The educational and service perspectives are discussed, from development to implementation. PMID- 7997291 TI - The work of the National Advisory Board on Ethics in Reproduction. PMID- 7997293 TI - Exploring the scientific bases of holistic nursing. AB - This paper reviews research findings that validate the use of holistic interventions in nursing practice. The resurgence of interest in alternative therapies for health care requires the dissemination of facts about their efficacy. Reviewed herein are the interventions of relaxation, therapeutic touch, imagery, and humor. The author contends that these interventions are both appropriate and advantageous additions to nurses' repertoires and calls for increased acceptance of the phenomenologic methods already developed for the unique science of nursing. PMID- 7997292 TI - Bioethics and nursing. AB - Today, more than ever, nurses and their patients need to keep pace with the technologic revolution in patient care. There are choices now in health care that patients or their caregivers in the past did not have to face. In making these ethical decisions, nurses rely on systematic problem solving, legal advice, ANA Code of Ethics, Nurse Practice Acts, Patient Bill of Rights, clergy, colleagues, and hospital protocols, along with the examination of their own ideals and morals. Ethics is a complex field, and one must look beyond the surface to examine the incidents in the order in which they occurred. In most situations, therefore, one must look past simplistic statements made about the case. After a detailed analysis, what becomes apparent is that the nurse is not necessarily in the wrong. PMID- 7997294 TI - Fetal well-being II: health care providers' responsibility in late pregnancy. PMID- 7997295 TI - A precepted leadership course based on Bandura's social learning theory. AB - Transition from student to registered nurse (RN) has long been cited as a difficult time for new graduates entering health care. Bandura's (1977) theory of social learning guided a revision of a nursing leadership course required of baccalaureate student nurses (BSNs) in their final semester. The preceptorship allowed students to work closely with and to practice modeled behaviors of RNs and then receive feedback and reinforcement from both the preceptor and the supervising faculty member. Students were thus prepared to function better in the reality of the practice setting. Positive outcomes were experienced by students, BSN preceptors, faculty, and nurse administrators. PMID- 7997296 TI - [Pain in an arthritis hip; not always 'old news']. PMID- 7997298 TI - [Sternoclavicular dislocation]. PMID- 7997297 TI - [The role of cytokines in the pathogenesis of inflammatory intestinal diseases]. PMID- 7997299 TI - [Mortality among young people: causes and background]. AB - OBJECTIVE: To study the mortality pattern among adolescents and young adults (15 24 years of age) in the Netherlands, 1983- 1992. DESIGN: Retrospective study. SETTING: Centraal Bureau voor de Statistiek (Statistics Netherlands). METHOD: Based on central registration and coding of all cause of death certificates in the Netherlands, the results of 10 years for the age group of 15-24 years were arranged according to the Chapters of ICD-9 and subdivided where necessary. Changes during this period were also studied. The findings were compared with those obtained in other countries. RESULTS: Most young people (61.5% of the men, 45.2% of the women) died of external causes. Traffic accidents and suicide ranked first and second in this category. Among natural causes, (malignant) neoplasms were most important, followed by diseases of the nervous system and sensory organs, diseases of the circulatory system and congenital anomalies. There was a group of 8.8% classified as 'symptoms, signs and ill-defined conditions' of which over 90% were registered as 'cause unknown', mainly (65.8%) due to missing certificates of young people who died abroad. The course in time showed a slight decrease of all causes, particularly of external causes. Compared with other countries (Europe, USA) the results in the Netherlands stand out favourably. CONCLUSION: A further decline of mortality in young people could be achieved by unrelenting efforts to prevent traffic accidents and other accidental or suicidal deaths. Apart from this, life expectancy in the young will gain by prevention and/or early treatment of malignancies, infectious diseases and congenital conditions. A higher autopsy rate would solve some uncertainties. PMID- 7997300 TI - [The ultimate fate of articles rejected for publication in the Nederlands Tijdschrift voor Geneeskunde]. AB - OBJECTIVE: Determining the fate of articles rejected for publication by the Dutch Medical Journal (Nederlands Tijdschrift voor Geneeskunde, NTvG). DESIGN: Retrospective. SETTING: Editorial office of the NTvG. METHOD: Using a Medline search and questionnaire for authors, the fate of 108 manuscripts, (definitively) rejected for publication in the second half of 1992, was determined. Articles were divided according to the various headings, which they received upon submission. RESULTS: Of all the 108 rejected manuscripts, 14 were found in Medline, of which 5 had already been published, when submitted to the NTvG (4 of these were unannounced duplicate publications). The inquiry had a response rate of 84%; 93 manuscripts could be included in the study. The over-all publication percentage of rejected articles was 60% ((46/93 (49%) published, 10/93 (II%) accepted for publication)); 5 articles were published twice in different journals. The mean time lapse between rejection and publication of the articles published after rejection was II months. Of all articles published or accepted for publication (n = 62; duplicate publications included) 25 appeared in an English journal, 37 in a Dutch journal. CONCLUSION: Of articles rejected by the NTvG 60% is eventually published in another journal. PMID- 7997302 TI - [The Law on Medical Treatment Agreement]. PMID- 7997301 TI - [Skin reactions attributed to the use of bromhexine]. AB - Since 1972, the Netherlands Centre for Monitoring of Adverse Reactions to Drugs has received 22 reports of skin reactions attributed to use of bromhexine. The reports concerned II men and II women. The ages ranged between 5 months and 88 years. The skin reactions occurred within one to 30 days after starting the use of bromhexine. Most skin reactions consisted of generalised urticaria. Other reports concerned once an angioedema and once an anaphylactic reaction. Most patients recovered completely after cessation of bromhexine without further treatment. PMID- 7997303 TI - [The Law on Medical Treatment Agreement: viewpoint of the professional group]. PMID- 7997304 TI - [Infectious arthritis?]. PMID- 7997305 TI - [Quilts as a risk factor for crib death]. PMID- 7997306 TI - Health care fraud and abuse--revisited. PMID- 7997307 TI - What is the current status of management of the patient with exercise-induced asthma? AB - Exercise-induced asthma (EIA) is a very common and troublesome disease frequently impairing optimal athletic performance. Although described as early as the second century A.D. and widely known since 1972, EIA often goes unrecognized by both patient and physician. The goals of treatment are to minimize symptoms thus allowing the athlete to participate fully in a broad array of activities and to utilize the most effective pharmacologic drugs available. The recognition and treatment of exercise-induced asthma (EIA) have made significant progress since 1972 when United States swimmer, Rick Demont had his Olympic gold medal award rescinded because of traces of ephedrine were detected in his urine. Lessons from this episode paid dividends subsequently; in preparation for the 1984 Olympic games in Los Angeles, the U.S. Olympic Committee developed a screening program which identified 67 U.S. team members with EIA. Astoundingly, several of these world-class athletes did not realize they had asthma. Affected individuals were counseled on the prevention of asthma and also on the effective use of medications; 41 won medals in various competitions including track and field, wrestling, basketball, cycling, swimming and rowing. Despite this resounding success, many athletes at all levels of competition still suffer from unrecognized or under-treated EIA despite knowledge of the problem since the second century A.D.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7997308 TI - Burst fracture of the twelfth thoracic vertebra in a middle aged man with osteoporosis. PMID- 7997309 TI - Breast cancer screening: recent trends in the use of mammography in Nebraska. AB - Although the efficacy of screening mammography has been surrounded in controversy of late, the evidence that it can reduce breast cancer mortality among women 50 74 years of age is extremely sound. In Nebraska, data from the state's Behavioral Risk Factor Survey show, that during the years 1988 to 1992, the percentage of women age 50 years and older who had ever had a mammogram rose from 50% to 65%, while the percentage of women of the same age who had had a mammogram within the past year rose from 24% to 34%. Nebraska BRFS data also show that the percentage of women 50 years of age and older who have had a mammogram within the past year varies considerably by age, income, education, and county of residence. Among women who have not had a mammogram within the past year, 66% reported that they had seen a physician within the past year for a routine check-up. Prompt and appropriate follow-up of abnormal findings by both physicians and health-care organizations is also essential to ensure the maximum benefit of screening mammography. PMID- 7997310 TI - The pregnant patient experiencing trauma. PMID- 7997312 TI - A day in the life of a nurse practitioners. PMID- 7997311 TI - Health reform: an ethical dilemma for nurses? PMID- 7997313 TI - [Multiple cerebral aneurysms disclosed by subarachnoid hemorrhage. Apropos of 60 cases]. AB - In a series of 60 consecutive patients, 137 multiple aneurysms (An) were discovered after subarachnoid hemorrhage. Multiple An were mostly double (83 % of the patients). The incidence of middle cerebral artery An was 42 %, internal carotid artery An 25.5 %, anterior communicating artery An 15 %. Both angiography (A degree) and CT scan could identify the ruptured An in 56 cases or at least the side of the ruptured An in the remaining 4 cases. Among the routine A degree criteria used to determine which one of the An had bled the most reliable ones appears to be: the existence of vasospasm of the parent artery, the bigger size of the sac, the irregular wall of the sac. The incidence of rupture is the highest in anterior communicating artery An (16/21). When an An located on the polygon of Willis is associated to a distal An, the former ruptures in 17 cases/18. All ruptured An were treated during the first operative session. In 47 patients (78.3%) all the An, ruptured and asymptomatic, were treated during the first procedure or in one or two additional surgical sessions. In 13 patients (22.7%) for several reasons only ruptured An and asymptomatic An that could be reached via the same craniotomy were treated. There was no morbidity or mortality related to the surgical treatment of asymptomatic An. PMID- 7997314 TI - [Initial prognostic factors of aneurysmal subarachnoid hemorrhage]. AB - The purpose of this retrospective study is to explain, using a total of 210 consecutive patients with aneurysmal subarachnoid hemorrhage, the survival by several prognostic factors measured at the admission time. A multivariate analysis using the Cox proportional hazards model allowed one to recognize five prognostic factors: secondary arterial hypertension (risk ratio (RR) = 1.8; p = 0.03), the Hunt and Hess grade-3 (RR = 3.3; p = 0.002), the Hunt and Hess grade-4 (RR = 7.3; p = 0.007), and the hunt and Hess grade-5 (RR = 5.8; p = 0.03), the Fisher grade-3 (RR = 2; p = 0.01), and the Fisher grade-4 (RR = 2; p = 0.001). The determination of a prognostic score for each patient (using the coefficients of selected prognostic factors) allowed one to establish 3 prognostic stages with survival probabilities significantly different (p = 0.00005); stage-1; survival rate after 150 days (SR) = 97 %, confidence interval of 95 % (CI) = [0.90; 0.99], stage-2: SR = 66 %, CI = [0.56; 0.74], stage-3; SR = 34 %, CI = [0.17; 0.54]. The relative death risk for the stage-2 was 14 times higher than that for stage-1 (p = 0.00005), and the relative death risk for the stage-3 was 36 times higher than that for stage-1 (p = 0.00005). The age, the essential arterial hypertension, the sex and the angiographic classification of George have no prognostic value. The rebleeding incidence was correlated with prognostic stages (respectively from stage-1 to the stage-3: 8 %, 14 %, 34 %).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7997316 TI - [Neurosurgical treatment of intracranial aneurysms]. AB - This text summarizes the course organized for residents and trainees by the Societe de Neurochirurgie de Langue Francaise. It was presented by the authors during the annual winter meeting held in Paris in December 1992. The aim of this course was to discuss all the technical points needed to achieve safely a microsurgical clipping of an intracranial aneurysm of the anterior circulation. Although many of these technical points discussed can apply to any kind of intracranial aneurysm, the very specific difficulties of the treatment of giant aneurysms or posterior circulation aneurysms were not mentioned. The usual pterional approach is described. The need of having a slack brain to perform easily the dissection of the aneurysm is stressed. Standards of hemodynamic control during surgery are described either with the use of a total or a proximal temporary clipping under the electrophysiologic control of the somesthetic evoked potential. Prevention of peroperative cerebral ischemia and brain protection are discussed. Dissection of the aneurysm is presented step by step until clipping. Different ways of clipping are discussed after a short description of the characteristics and composition of various available clips. How to deal with a premature intra-operative rupture of the aneurysm is also discussed. The last chapter describes step by step the approach and clipping of the four most frequent aneurysm locations i.e. at the posterior face of the intracranial internal carotid artery, the intracranial carotid bifurcation, the middle cerebral artery, and the anterior communicating artery. PMID- 7997315 TI - [Stereotaxic biopsies of pineal tumors. Comments on their risk and implication apropos of 370 cases]. AB - 370 stereotactic biopsies of pineal region tumors, from 15 neurosurgical centers in France have been reviewed with the goal to evaluate the mortality/morbidity rates and diagnostic yield of this procedure. The impact of neuroradiological means of localisation, the probe trajectory, the type of biopsy instrument, the time of shunting are discussed in order to maximize the diagnostic yield and minimize the mortality/morbidity rates. Stereotactic biopsy contribution, as compared to other diagnostic methods, in pineal region tumors was evaluated. The mortality rate was 1.3 % (5 patients of 370), 3 patients suffered severe neurological complication. In relation to the large number of patients in this study, we can assess that the mortality rate of stereotactic biopsy in this region doesn't significantly exceed that of stereotactic brain tumor biopsies in general. PMID- 7997317 TI - [Guy Piganiol (1920-1992)]. PMID- 7997318 TI - [Jean Bancaud (1921-1993)]. PMID- 7997319 TI - Signs to look for in a battering personality. PMID- 7997320 TI - Nurses caring for nurses: what is recovery? PMID- 7997321 TI - Ethnic pharmacology: a neglected area of cultural competence. PMID- 7997322 TI - VEP in albinism. PMID- 7997323 TI - Herpetic Eye Disease Study. A controlled trial of oral acyclovir for herpes simplex stromal keratitis. AB - PURPOSE: To evaluate the efficacy of oral acyclovir in treating stromal keratitis caused by herpes simplex virus (HSV) in patients receiving concomitant topical corticosteroids and trifluridine. METHODS: The authors performed a randomized, double-masked, placebo-controlled, multicenter trial in 104 patients with HSV stromal keratitis without accompanying HSV epithelial keratitis. Sample size was chosen so that a 5%, one-tailed test would have an 80% chance of detecting a doubling of the median time to treatment failure. Patients were randomized to receive a 10-week course of either oral acyclovir (400 mg 5 times daily, n = 51) or placebo (n = 53). All patients also received a standard regimen of topical prednisolone phosphate and trifluridine. Ophthalmologic examinations were performed weekly during the 10-week treatment period, every 2 weeks for an additional 6 weeks, and at 6 months after entry into the trial. RESULTS: The median time to treatment failure (defined as worsening or no improvement of stromal keratitis or an adverse event) was 84 days (95% confidence interval, 69 93 days) for the acyclovir group and 62 days (95% confidence interval, 57-90 days) for the placebo group. By 16 weeks, 38 patients (75%) in the acyclovir group and 39 patients (74%) in the placebo group had failed treatment. Also by that time, the keratitis had resolved with trial medications, and there was no subsequent worsening in nine patients (18%) in the acyclovir group and ten (19%) in the placebo group. None of these results were significantly different between the two groups. However, visual acuity improved over 6 months in significantly more patients in the acyclovir group than in the placebo group. CONCLUSION: There was no statistically or clinically significant beneficial effect of oral acyclovir in treating HSV stromal keratitis in patients receiving concomitant topical corticosteroids and trifluridine with regard to time to treatment failure, proportion of patients who failed treatment, proportion of patients whose keratitis resolved, time to resolution, or 6-month best-corrected visual acuity. Visual acuity improved over 6 months in more patients in the acyclovir group than in the placebo group. PMID- 7997324 TI - Herpetic Eye Disease Study. A controlled trial of topical corticosteroids for herpes simplex stromal keratitis. AB - PURPOSE: To evaluate the efficacy of topical corticosteroids in treating herpes simplex stromal keratitis. METHODS: The authors performed a randomized, double masked, placebo-controlled, multicenter clinical trial of 106 patients with active herpes simplex stromal keratitis who had not received any corticosteroids for at least 10 days before study enrollment. Patients were assigned to the placebo group (n = 49) or the steroid group (topical prednisolone phosphate; n = 57); both regimens were tapered over 10 weeks. Both groups received topical trifluridine. Visual acuity assessment and slit-lamp biomicroscopy were performed weekly for 10 weeks, every other week for an additional 6 weeks or until removal from the trial, and at 6 months after randomization. RESULTS: The time to treatment failure (defined by specific criteria as persistent or progressive stromal keratouveitis or an adverse event) was significantly longer in the steroid group compared with the placebo group. Compared with placebo, corticosteroid therapy reduced the risk of persistent or progressive stromal keratouveitis by 68%. The time from randomization to resolution of stromal keratitis and uveitis was significantly shorter in the steroid group compared with the placebo group even though both groups included patients who were removed from the study and treated with topical corticosteroids according to best medical judgment. Nineteen (33%) of the steroid-treated patients and 11 (22%) of the placebo-treated patients completed the 10 weeks of protocol therapy and had stable, noninflamed corneas after 16 weeks. At 6 months after randomization, no clinically or statistically significant differences in visual outcome or recurrent herpetic eye disease were identified between the steroid and placebo groups. CONCLUSIONS: The topical corticosteroid regimen used in this study was significantly better than placebo in reducing persistence or progression of stromal inflammation and in shortening the duration of herpes simplex stromal keratitis. Postponing steroids during careful observation for a few weeks delayed resolution of stromal keratitis but had no detrimental effect as assessed by visual outcome at 6 months. PMID- 7997325 TI - Color dissociation artifacts in double Maddox rod cyclodeviation testing. AB - BACKGROUND: The double Maddox rod test, based on a red Maddox rod in front of one eye and a clear Maddox rod in front of the other, is used to measure cyclodeviation, typically in patients with superior oblique muscle pareses. Discrepant results between the double Maddox rod test and other torsion measures, and reports of "paradoxic" cyclodeviation in the normal eye of some patients with superior oblique paresis, suggest the two-color format of the double Maddox rod test may produce artifactual torsion measures. METHODS: Forty patients with superior oblique paresis were tested twice using the double Maddox rod test, reversing the red and white Maddox rods between eyes for the second test, and 18 were tested further with same-color red or clear Maddox rods in front of both eyes. RESULTS: With the standard double Maddox rod test, 33 (83%) of 40 patients localized their cyclodeviation to the eye viewing through the red Maddox rod, irrespective of laterality of the paresis or fixation preference. In all 33 patients, laterality of the perceived torsion changed between eyes when testing was repeated with red and white Maddox rods interchanged between eyes. With same color Maddox rods before both eyes, 17 (94%) of 18 patients localized extorsion to the paretic eye. There was 7.6:1 ratio of luminance transmission and a 1.6:1 ratio of grating spatial frequency bandpass in the plano meridian between the clear and red Maddox rods, which appear to be responsible for the double Maddox rod test artifact. CONCLUSION: The traditional double Maddox rod test may produce artifactual cyclodeviation measurements. An alternative version of the test, based on same-color Maddox rods in front of both eyes, is proposed. The relatively high spatial frequency bandpass characteristics of the plano meridian of the Maddox rod (as high as 20/25 Snellen equivalent resolution through the clear Maddox rod) also suggests double Maddox rod testing should be conducted in a dark room to avoid biases from visual environment cues. PMID- 7997326 TI - A case of unilateral congenitally enlarged extraocular muscles. AB - BACKGROUND: Enlargement of extraocular muscles is an uncommon finding in children. Little has been written in the literature about possible causes. METHODS: The authors present the clinical findings of a young girl who had unilateral congenitally enlarged extraocular muscles at 8 months of age. She underwent computed tomography (CT) and magnetic resonance imaging (MRI) scans, systemic assessment, and extraocular muscle biopsy to determine a cause for the enlarged muscles. RESULTS: The patient had a unilateral left esotropia and hypotropia at birth that was nonprogressive. High-resolution CT and MRI scans showed enlargement of the left inferior rectus, lateral rectus, and medial rectus muscles. Strabismus surgery undertaken at 2 years of age showed that the affected muscles were restricted on forced duction testing but were macroscopically normal in appearance. A biopsy specimen of the left lateral rectus muscle was processed for histologic, histochemical, and electron microscopic studies, but no abnormal pathologic findings were found. CONCLUSION: This patient's constellation of findings appears to be unique: it does not follow any previously reported pattern of disorders of extraocular muscle enlargement. PMID- 7997327 TI - Emulsified anterior chamber silicone oil and glaucoma. AB - PURPOSE: This retrospective study was undertaken to assess the occurrence of postoperative anterior chamber emulsified silicone oil after intravitreal instillation and to examine the relation between such emulsification and new postoperative glaucoma. METHODS: Forty-eight consecutive eyes received intravitreal silicone oil, were followed for at least 1 year, and were evaluated postoperatively by gonioscopy on at least one occasion. Eight eyes received 1000 cs oil, and 40 eyes received 5000 cs oil from which low molecular weight contaminants were removed. All aphakic and pseudophakic eyes received an inferior iridectomy. Oil was removed in 19% of eyes during follow-up. RESULTS: Fifty-six percent of eyes manifested anterior chamber emulsified oil postoperatively. The oil was typically identified only on gonioscopy. This complication developed in 50% of eyes receiving 1000 cs oil and 58% of eyes receiving highly homogeneous 5000 cs oil. Of the 48 eyes, new postoperative glaucoma best explained by interval angle oil emulsification developed in 5 (10%). CONCLUSION: Anterior chamber oil emulsification occurred frequently, despite inferior peripheral iridectomy in aphakic or pseudophakic eyes and the use of highly purified, higher viscosity oil in 83% of eyes. In this series, new glaucoma in the setting of angle oil emulsification only developed in 10% of eyes. The glaucoma was managed medically in four of five patients. PMID- 7997328 TI - Are there acceptable anterior chamber intraocular lenses for clinical use in the 1990s? An analysis of 4104 explanted anterior chamber intraocular lenses. AB - PURPOSE: The authors pose the question as to whether there are any anterior chamber intraocular lenses (AC IOLs) acceptable for clinical use in the 1990s. METHODS: Data on the incidence and types of complications of 4104 AC IOLs that were submitted to the Center for IOL Research from 1982 to 1993 were retrieved from the laboratory database and analyzed using cumulative frequency calculations and the chi-square test. Normalized explantation rates were related to implantation rates that were derived from market-share analysis. RESULTS: Of 4104 explanted IOLs, 50% were closed-loop designs (n = 2095/4104); 26% (1100/4104) were miscellaneous, older designs; and 22% (919/4104) were open-loop lenses. The most important complications were corneal pathology (2065/4104) and inflammation (1370/4104). Closed-loop designs were responsible for almost 80% of corneal pathology, with an increasing complication rate with ongoing implant duration (P < 0.0001). Open-loop AC IOLs showed, in relation to their normalized rate of implantation, a significantly lower rate of complications and explantations (P < 0.01). CONCLUSION: Complication rates of flexible, open-loop AC IOLs are much lower than previously assumed. They should be distinguished clearly from most older AC IOL designs. Consideration of these lenses as an alternative to sutured posterior chamber IOLs for secondary or exchange implantation may be warranted for selected clinical indications. They also could provide an alternative to the aphakic spectacle rehabilitation program in developing countries, which will have a positive impact on the overwhelming backlog of patients with cataract in the underprivileged world. PMID- 7997329 TI - Coccidioidomycosis iridocyclitis. AB - BACKGROUND: Coccidioidomycosis has reached epidemic proportions in the southwest region of the United States. Despite the greater numbers of cases, isolated anterior segment ocular coccidioidomycosis in the absence of systemic infection continues to be rare, although its incidence may be increasing. METHODS: Two patients without clinical evidence of systemic disease and one patient with previously treated pulmonary coccidioidomycosis had granulomatous iridocyclitis and iris nodules that were unresponsive to corticosteroid therapy. All three patients underwent iris biopsy, anterior chamber tap, and washout for histopathologic diagnosis of anterior segment disease, and all subsequently received systemic antifungal therapy. Two patients also received multiple intraocular injections of amphotericin B. RESULTS: Papanicolaou and hematoxylin eosin-stained preparations of anterior chamber tap and biopsies of the iris in each of these patients showed fibrinopurulent or granulomatous inflammatory exudate with intact and disrupted Coccidioides spherules. Despite aggressive systemic and intraocular therapy, one patient required enucleation for a blind, painful eye. The other two patients continue to have limited visual acuity but with at least partial resolution of the intraocular lesions. CONCLUSIONS: Ocular coccidioidomycosis without clinical evidence of systemic involvement is rare. Isolated anterior segment disease is also uncommon; however, because of the current epidemic in the southwest region of the United States, ocular coccidioidomycosis should be considered in any patient who traveled through or lived in endemic areas and who has a granulomatous iridocyclitis associated with iris mass that is unresponsive to corticosteroid therapy. PMID- 7997330 TI - Capnocytophaga keratitis. A clinicopathologic study of three patients, including electron microscopic observations. AB - BACKGROUND: Histopathologic studies of this unusual keratitis caused by Capnocytophaga species have not been reported previously. METHODS: The authors report the light microscopic and ultrastructural findings of three patients with a distinctive necrotizing keratitis caused by an anaerobic gram-negative bacillus. In three patients, ages 19, 81, and 91 years, a necrotizing stromal keratitis developed; two of these patients had a previous penetrating keratoplasty for pseudophakic bullous keratopathy. The first patient did not have ocular surgery previously and was treated initially for presumed Acanthamoeba keratitis. RESULTS: By light microscopy, all three keratectomy specimens were strikingly similar and showed a necrotizing and/or suppurative stromal keratitis displaying myriad slender, fusiform, gram-negative bacilli located anterior to Descemet's membrane and extending into the deep corneal stroma, assuming a "picket fence" appearance. Cultures of the cornea in case 1 grew Capnocytophaga ochracea. For the remaining two patients, a diagnosis presumptively was made based on characteristic histopathologic features. Results of electron microscopic examination showed numerous bacilli that were mostly extracellular; occasional organisms were phagocytosed by macrophages. CONCLUSION: The histopathologic features of Capnocytophaga keratitis are unique; therefore, a presumptive diagnosis can be made based on the morphology and location of the bacilli in the keratectomy specimens. To the authors' knowledge, this is the first study describing the typical histopathologic and electron microscopic findings of Capnocytophaga keratitis. PMID- 7997331 TI - Impression debridement of corneal lesions. AB - PURPOSE: The technique of impression cytology using cellulose acetate filter paper as a debriding agent was evaluated. METHODS: Lesions were assessed using a slit-lamp biomicroscope before and after the impressions were taken and appropriate antibiotic therapy was started. The filter paper impressions were stained with hematoxylin-eosin and examined by light microscopy. The 72 corneal ulcers and three cases of suture infiltration around exposed corneoscleral cataract-related sutures were effectively debrided. Five of the six foreign bodies and all of the filaments in the six filamentary keratitis cases were removed with minimal damage to the surrounding cornea. RESULTS: Results of microscopic examination showed that the cells that were transferred to the filter paper were primarily the affected cells. In corneal ulcers, the degenerated epithelial cells, inflammatory cells, and organisms were removed. The inflammatory cells superimposed on affected epithelial cells in suture infiltration and the filaments of filamentary keratitis were removed. In cases of superficial corneal foreign bodies, the foreign bodies overlying a sheet of degenerated epithelial cells were lifted up. CONCLUSION: "Impression debridement" improves the quality and efficiency of debridement for most of these conditions, with much less risk to the surrounding tissue than the conventional techniques. Besides being an adjunct to therapy, it simultaneously provides replicas of the lesions that give accurate histologic details after microscopic evaluation. PMID- 7997332 TI - Predictors of occult scleral rupture. AB - PURPOSE: To determine which signs are sensitive and specific in the setting of trauma to establish the diagnosis of an occult scleral rupture. METHODS: The charts of patients with presumed scleral rupture were identified retrospectively. The ocular findings among the patients who had a rupture based on findings at surgery were compared with those patients who were noted to have normal findings at surgery. RESULTS: Visual acuity worse than 20/400, decreased intraocular pressure, intraocular pressure less than that in the nontraumatized eye, and an afferent pupillary defect were all significant indicators of an open globe. CONCLUSION: Determining the likelihood of an occult rupture can be facilitated by noting the presence or absence of those indicators that are significant and carry a high specificity. PMID- 7997333 TI - Serial foveal densitometry and visual function after retinal detachment surgery with macular involvement. AB - PURPOSE: Fundus reflection densitometry was used as an objective means for monitoring the recovery of foveal cone photopigments in nine patients who underwent anatomically successful surgery of a rhegmatogenous retinal detachment with macular involvement. METHODS: Postoperative assessment of foveal densitometry, visual acuity, color matching, and the Amsler grid were performed at repeated intervals for up to 14 months. RESULTS: Gradual recovery of foveal cone photopigments was found in all patients 1 to 14 months after surgery, with considerable interindividual variation. Maximal recovery to values equalling those in the fellow eye was found in only one patient with a macular detachment duration of 5 days. All other patients had final photopigment densities below those of the fellow eye. The length of the preoperative detachment period was inversely related to the recovery of photopigment. The recovery of photopigment seems to increase further in the second year after surgery. Visual acuity increased rapidly in all patients during the first 6 months after surgery, to levels ranging between 20/67 and 20/25; thereafter, visual acuity did not change. A return to normal color matching after an episode of pseudoprotanomaly was found in four of nine patients, whereas pseudoprotanomaly remained in five patients. Complete resolution of metamorphopsia after surgery was seen only in the patient who had the shortest detachment duration. Metamorphopsia was consistent with decreased foveal cone photopigment densities. CONCLUSION: Foveal densitometry shows a slow recovery of the cone photopigments after reattachment, probably because of regrowth and realignment of the cone photoreceptor outer segments and metabolic recovery of the retinal pigment epithelium-cone photoreceptor complex. Recovery of photopigment, color matching, and metamorphosia follow a slower time course than recovery of visual acuity. PMID- 7997334 TI - Vascular targeting in photodynamic occlusion of subretinal vessels. AB - PURPOSE: To evaluate the potential of photodynamic therapy (PDT) using benzoporphyrin derivative (BPD) for occlusion of subretinal neovascular membranes, the authors studied efficiency and collateral damage of PDT-induced photothrombosis in the rabbit choriocapillary layer. METHOD: Benzoporphyrin derivative, a new photosensitizer, currently in clinical trials for tumor therapy, was used. Low-density lipoprotein served as a carrier to enhance selective targeting of vascular endothelial cells. RESULTS: Complete choriocapillary occlusion was achieved at a BPD dose of 2 mg/kg and a radiant exposure as low as 10 J/cm2. When PDT was performed 3 hours after BPD application, damage to the neural retina was minimal. Only inner photoreceptor segments showed mitochondrial swelling probably secondary to choroidal ischemia. Bruch's membrane remained intact. Retinal pigment epithelium was invariably damaged as seen with other photosensitizers. CONCLUSION: Compared with photocoagulation BPD-PDT allows endothelial-bound intraluminal photothrombosis, sparing important structures such as neural retina and Bruch's membrane. It may thus provide a more selective treatment of juxtafoveal and subfoveal neovascular membranes. PMID- 7997335 TI - The association of alcohol consumption with the incidence and progression of diabetic retinopathy. AB - PURPOSE: To investigate the association of alcohol consumption with the incidence and progression of diabetic retinopathy. METHODS: The population consisted of a cohort of adult younger-onset (diagnosis received before 30 years of age and taking insulin, n = 439) and older-onset (diagnosis received after 30 years of age, n = 478) persons with diabetes examined from 1984 to 1986 and again from 1990 to 1992. The outcomes were incidence of retinopathy, progression, and progression to proliferative retinopathy. Retinopathy was determined by grading of stereoscopic color fundus photographs. Alcohol consumption was determined by questionnaire and summarized as average or recent consumption. The proportion of heavier drinkers was small, 6% of younger-onset and 4% of older-onset persons. RESULTS: In the younger-onset group, progression of retinopathy occurred in 62%, 51%, 61%, and 71% of nondrinkers, light, moderate, and heavier drinkers, respectively, based on average intake (P = 0.28). Based on recent intake, 55%, 46%, 63%, and 69% of nondrinkers, light, moderate, and heavier drinkers, respectively, progressed (P = 0.10). A similar trend is seen for incidence of retinopathy, but the sample sizes are small. No association is seen with progression to proliferative diabetic retinopathy. After controlling for age, sex, and glycemia in a logistic regression model, alcohol intake is not associated with progression of retinopathy. In the older-onset group, alcohol intake is not related to the incidence or progression of retinopathy. CONCLUSION: Alcohol consumption in moderation (< or = 1 oz/day) does not appear to affect the occurrence of diabetic retinopathy. PMID- 7997336 TI - The relation of socioeconomic factors to age-related cataract, maculopathy, and impaired vision. The Beaver Dam Eye Study. AB - PURPOSE: To investigate the relations between socioeconomic factors and the prevalence of age-related cataract, maculopathy, and visual impairment. METHODS: A population-based sample of 4926 people 43 to 86 years of age was examined from 1988 to 1990. Education, income, employment status, marital status, nuclear sclerosis, cortical, and posterior subcapsular cataract, age-related maculopathy, and impaired vision were all ascertained using standard protocols. RESULTS: While controlling for age, sex, diabetes status, multivitamin use, alcohol consumption, and cigarette smoking, less education was significantly associated with nuclear and cortical cataract, and lower income was significantly associated with cortical and posterior subcapsular cataract and impaired vision. There was a "U shaped" relation between income and cataract surgery. Neither income nor education was related to age-related maculopathy. There was no relation of marital status to cataract status or age-related maculopathy. CONCLUSION: These data suggest that education and income are associated with cataract, cataract surgery, and impaired vision. These relations were not explained by other risk factors measured in the study. PMID- 7997337 TI - Analyses of 94 consecutive spinal cord injury patients using ASIA definition and modified Frankel score classification. AB - Serial neurological examinations were analysed on 94 consecutive spinal cord injury (SCI) patients admitted for rehabilitation to the Swiss Paraplegic Center at the Clinic Balgrist Zurich, Switzerland between 1987 and 1992. Patients' data were examined adopting ASIA and modified Frankel definitions in order to compare the two classifications in terms of consistency and prognostic value. The modified Frankel definition was subdivided into five categories (A, B, C, D and E). On admission (discharge) 43 (37) patients were classified as Frankel A, 23 (11) patients in group B, 26 (42) patients in group C, 2 (2) patients as Frankel D and 0 (2) patients in group E. A qualitative analysis of the results on the base of a maximal score of 100 points (A = 0, B = 25, C = 50, D = 75 and E = 100 points) suggested a mean score improvement from 21.5 (+/- 22.5) to 29.0 (+/- 26.3) or 7.5 (+/- 7.1), regarding all 94 patients during follow up (admission/discharge). The median improvement was one modified Frankel grade (A/B to B/C). No detailed assessments were yielded concerning motor and sensory functions. Using ASIA definition, a continuous numerical score of motor and sensory function was observed. Recovery during follow up was determined by detailed motor and sensory function. For all 94 patients (quadriplegics and tetraplegics), the average motor recovery according to the ASIA definition was 9.4 (+/- 9.6). The mean ASIA motor score improved from 52.2 (+/- 17.3) on admission to 61.6 (+/- 17.9) on discharge.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7997338 TI - Transverse myelitis--neurophysiological and MRI correlation. AB - Acute transverse myelitis (ATM) rarely involves the cervical spinal cord. We report on two patients with ATM and cervical cord involvement. Magnetic resonance imaging (MRI) revealed high intensity signals in T2 extending far beyond the sensory level in both patients. Motor evoked potential (MEP) was unrecordable in all but one limb, and there it was marginally prolonged. Tibial somatosensory evoked potential (SEP) was unrecordable while median SEP was normal in both patients. Both MEP and SEP correlated with their respective clinical deficits but MEP seemed to correlate better with the MRI changes. PMID- 7997339 TI - A retrospective study of hyponatremia in tetraplegic/paraplegic patients with a review of the literature. AB - The aetiology of hyponatremia in tetraplegic patients is multifactorial and includes not only general factors such as the use of diuretics and the intravenous infusion of hypotonic fluids, but also certain mechanisms which operate in the spinal cord injured: decreased renal water excretion due to both intrarenal and arginine vasopressin dependent mechanisms (resetting of the osmostat), coupled with habitually increased fluid intake, and the ingestion of a low salt diet. Between 1984 and 1993 we treated 28 episodes of hyponatremia in 19 patients (males: 10; females: 9). Fourteen were tetraplegic and five paraplegic (thoracic lesion in four and lumbar lesion in one). Six patients were asymptomatic during seven episodes of hyponatremia which were detected during routine blood tests. Seven patients were suffering from an acute chest infection, three had an acute urinary tract infection, one had an infected ischial pressure sore and a 69 year old paraplegic patient had bronchopneumonia as well as sepsis from a gangrenous pressure sore in the supraanal region. The time interval between the onset of paralysis and occurrence of the first episode of hypnoatremia was less than a month in only four of the patients. The lowest plasma sodium level observed was less than 100 mmol/l in two, between 100 and 110 mmol/l in four, between 111 and 120 mmol/l in eight patients, and between 121 and 128 mmol/l in 14 cases. Six patients also had hypokalemia (K+ < 3 mmol/l). Only one patient had and elevated plasma creatinine (201 umol/l). Treatment of sepsis and fluid restriction were the mainstay of treatment with only two patients receiving hypertonic saline. All patients with underlying sepsis were treated with antibiotics, usually administered intravenously. The outcome was good in 26 of the 28 episodes. Two patients died: a 68 year old tetraplegic patient with consolidation of the left lung, cystadenocarcinoma of both ovaries and squamous cell carcinoma of the forehead who presented with generalised oedema, with a plasma sodium level of 118 mmol/l, and potassium of 2.4 mmol/l and who was treated with 2 N saline + potassium + frusemide; she died 1 day later. The only other death was that of a 78 year old female tetraplegic patient who 2 days after sustaining cervical trauma developed hyponatremia because of intravenous infusion of hypotonic fluids given at another hospital, presumably to correct hypotension. She recovered from hyponatremia with fluid restriction, but 3 days later she succumbed to bronchopneumonia and respiratory insufficiency. No patient developed central pontine myelinolysis.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 7997340 TI - Restoration of gait with orthoses in thoracic paraplegia: a multicentric investigation. AB - Twenty-eight patients with complete T3-12 traumatic paraplegia were fitted with hip guidance orthosis (HGO, four cases), reciprocating gait orthosis (RGO, 13 cases) or advanced reciprocating gait orthosis (ARGO, 11 cases). Patients were enrolled for 2 months-6 years (median 5 months) in six Italian rehabilitation centres engaged in a common prospective protocol, including a 6 month follow up. After 12-84 (median 20) rehabilitation sessions over a 3-16 week (median 7) period of specific training all of the patients could perform don-doff manoeuvres autonomously in 2.5-15 min (median 6.4), and could walk at least 30 m with a walker (15 cases) or forearm crutches (13 cases) at 10-50 cm/s (median 16.6). HGO patients tended to walk more slowly than the others. None of them could walk upstairs, while three out of 13 RGO patients and seven out of 11 ARGO patients could. Six months later, 21 patients still used the orthosis for 0.5-3 h daily (median 2). Only four patients used the orthosis to walk outdoors. As a median they could still attain the speed recorded at discharge. Six patients had decided to abandon the device, while one was wheelchair bound due to a recent spinal intervention. Neither clinical, demographic or locomotor variables, nor centre and type of orthosis appeared to be predictive of abandonment of the device. During either the training or the follow up periods, six out of 13 RGO and seven out of 11 ARGO had to be repaired by the orthotist 1-10 times (median 3). Thus, in our sample of paraplegics, walking with these orthoses appeared to be a promising form of exercise rather than an alternative to wheelchair locomotion. PMID- 7997341 TI - Urolume urethral wallstent in the treatment of detrusor sphincter dyssynergia. AB - Neuropathic voiding dysfunction with detrusor sphincter dyssynergia (DSD) is a common complication of spinal cord injury (SCI) and multiple sclerosis. Sphincterotomy has been recommended for treatment of DSD if the patient lacks the ability to do intermittent self catheterization. We report our preliminary results of the Urolume urethral wallstent for the treatment of DSD in 10 patients. The insertion technique proved simple, with a short hospital stay and low morbidity; however, its long term safety has not yet been established. PMID- 7997342 TI - Gangrenous cystitis in a paraplegic patient. Case report. PMID- 7997343 TI - Perineal xanthogranulomatous pseudotumor due to intermittent catheterization: a liposarcoma mimic. Case report. AB - A large perineal fatty tissue mass shown to be an encapsulated xanthogranulomatous reaction was found in a spinal cord injured man whose neuropathic bladder was for a long time being managed by clean intermittent catheterization, but who had chronic urinary tract infection. He was also known to be a chronic alcoholic. We would say that an alcohol numbed sensorium and multiple catheterizations led to recurrent small urethral perforations which in the setting of chronic bacteriuria promoted the unusual inflammatory mass. Appreciating the increasing use of clean intermittent catheterization for the spinal cord injured, we suspect that similar cases of 'xanthogranulomatous pseudotumors' will be found, and therefore we describe this most unusual clinical presentation. PMID- 7997344 TI - Posttraumatic pseudomenigocoele of cervical spine in a patient with skeletal fluorosis. Case report. AB - A case of fluorotic cervical compressive myelopathy precipitated by trauma is reported. The delayed neurological deterioration was due to a posttraumatic pseudomenincocele, the prompt treatment of which resulted in recovery. Posttraumatic pseudomeningocele is very rate; and certainly so in fluorosis, and thus has not been reported in the literature to date. PMID- 7997345 TI - The Pudenz Schulte medical prize for cerebrospinal fluid physiology. PMID- 7997346 TI - Barros TEP et al (1994). Patient with a lumbar vertebra fracture. Clinical discussion. Paraplegia 32: 137-141. PMID- 7997347 TI - Marine injuries. Prevention and treatment. AB - Penetrating wounds, stings, and inoculation of venom are common marine injuries to unwary walkers during the summer season. In many circumstances, foreign bodies such as wood splinters or small shards of glass can be removed readily with fine pointed forceps. Other times, objects may not be noticed until radiographic examination of the injured area. With deeply penetrated foreign bodies, attempts at removal must often be weighed against the likelihood of continued symptoms and damage should the object be left in the foot. This review presents methods of prevention and treatment for common sources of marine foot injuries. PMID- 7997348 TI - Reflex sympathetic dystrophy. A review of the literature and a long-term outcome study. AB - According to the literature, approximately half of all patients diagnosed with reflex sympathetic dystrophy respond to nonoperative treatment. Because no long term studies exist, however, the relapse rate and outcome of this condition are not known. In this paper, a historical review and a brief discussion of the theories of pathogenesis of the disease are presented. The results of treatment, as documented in the literature, are also presented. This paper also reports on 10 patients with reflex sympathetic dystrophy who were treated nonoperatively and for whom a follow-up of at least 1 year was documented. The patient population and short-term results are consistent with those found in the literature. Nine of the 10 patients were contacted for long-term follow-up at an average of more than 5 years after diagnosis. A significant number of patients experienced worsening of symptoms (56%) and reported that their condition negatively affected their activities of daily living (78%). Of those who were employed prior to diagnosis, 67% reported a job change or unemployment directly related to the disease. Therefore, the long-term results of nonoperative treatment are not as encouraging as is indicated in the literature. PMID- 7997349 TI - Open tibial fracture infections in asymptomatic HIV antibody-positive patients. AB - Fourteen patients with 15 open tibial fractures were examined retrospectively to compare postoperative infection rates of asymptomatic patients who tested positive or negative for the human immunodeficiency virus antibody (HIVab). All patients were treated with a standard open-fracture protocol. All of the HIVab positive patients developed postoperative infections. There were five postoperative infections in 4 patients; 3 of the 4 patients were HIVab-positive and 2 of these patients developed chronic osteomyelitis. The only other infection, in an HIVab-negative patient with insulin-dependent diabetes, resolved without complication. All other HIVab-negative patients had no complications. The infection rate for asymptomatic HIVab-positive patients with open tibial fractures was higher than that for HIVab-negative patients in our study. These data suggest that the HIV status of patients with open tibial fractures is relevant to treatment outcome. PMID- 7997350 TI - Percutaneous intramedullary pinning of proximal humeral fractures. AB - Proximal humeral fractures can usually be treated closed. However, even with an adequate closed reduction, these fractures are occasionally unstable, fail to remain reduced, and require operative intervention. A percutaneous intramedullary pinning technique is effective in stabilizing these fractures. Two cases that illustrate the adult and pediatric techniques for pin placement/application are presented. In the pediatric population, however, large multiple pins often cannot be used due to the size of the intramedullary canal, and fewer or smaller diameter pins are used. PMID- 7997351 TI - Pneumatic gouge versus standard method for iliac crest harvesting. AB - Fifty consecutive patients undergoing posterior lumbar fusion by a single surgeon were prospectively randomized in a study designed to evaluate the efficacy of using a pneumatic oscillating gouge to obtain posterior outer table iliac crest bone graft versus the standard method of using osteotomes and gouges. Variables analyzed included graft harvesting time, blood loss, weight of graft obtained, and graft site morbidity. Mean graft harvesting time with the pneumatic gouge was 1 minute 44 seconds (range, 1 min 5 sec to 3 min 15 sec) compared with the standard method time of 4 minutes 4 seconds (range, 2 min 15 sec to 8 min 56 sec) (P = 0.0001). Blood loss was also less, with a mean of 25.4 cc for the pneumatic gouge compared with 65.2 cc using the standard method (P = 0.0001). There were no complications with the graft site in either group. We conclude that the pneumatic gouge is a viable alternative to standard bone graft harvesting techniques. Benefits include shorter operative time and decreased blood loss without an increased morbidity. PMID- 7997352 TI - Preserving the posterior cruciate ligament in total knee arthroplasty. AB - A technique is described whereby a small island of bone at the posterior midline of the tibia is preserved during total knee replacement to protect the insertion of the posterior cruciate ligament. PMID- 7997353 TI - Autoamputation of the fingertips in an 11-year-old boy. AB - The following case is presented to illustrate the roentgenographic and clinical findings of a condition of interest to the orthopaedic surgeon. The final clinical and roentgenographic differential diagnoses can be found on the following pages. PMID- 7997354 TI - Vascular shear forces and atherogenesis: roles of shear-provoked endothelial viral infection and heme iron accumulation. PMID- 7997355 TI - Opioid properties of psychotropic analgesic nitrous oxide (laughing gas). PMID- 7997356 TI - The breath of life: legacies from virtuosos of biology, chemistry, and medicine. PMID- 7997357 TI - Defining the irritable bowel syndrome. PMID- 7997358 TI - Menstruation: an ethnophysiological defense against pathogens. PMID- 7997359 TI - Whither goest vivisection? Legislative and regulatory perspectives. PMID- 7997360 TI - Male homosexual desire: neurological investigations and scientific bias. PMID- 7997361 TI - [The future of transplantation surgery]. PMID- 7997362 TI - [Theme: organ transplantation]. PMID- 7997364 TI - [Status of organ donation in Iceland]. AB - According to Icelandic law, since 1991 the medico-legal criterion of death has been the cessation of brain function. Yet another law regulates the harvesting of organs for transplantation. A living donor must be at least 18 years of age, be fully informed, and not exposed to direct risk. Cadaver organs may be harvested provided the deceased has given consent in advance, or failing this if the next of kin gives consent. In the absence of explicit consent (i.e., presumed non consent), no organ may be harvested. PMID- 7997363 TI - [Scandiatransplant]. AB - Scandiatransplant is an organ exchange organisation serving a population of about 23 million inhabitants in the five Nordic countries, Iceland, Finland, Sweden, Norway and Denmark. Scandiatransplant maintains a central waiting list for Scandinavian patients scheduled for cadaver organ transplantation. Since its establishment in 1969, more than 13,000 cadaver renal transplants have been performed, and the numbers of liver, heart and lung transplantations are steadily increasing. PMID- 7997365 TI - [Terminal kidney failure, uremia care and kidney transplantation]. AB - In the Nordic countries, the annual figures for new patients scheduled for renal replacement therapy (i.e., dialysis or kidney transplantation) are 49 (Denmark), 55 (Finland), 65 (Norway) and 99 (Sweden) per million of the population (pmp). Some 40-50 of those patients are medically eligible for transplantation. If the transplant rate of the individual transplant centre or country is less, the waiting list will increase, as they do at some of the Nordic centres. The annual rate of transplants from living related donors, including spouses, varies from almost zero in Finland to nearly 20 pmp in Norway. The average age of recipients has increased with the increasing age of patients accepted for dialysis. Of the Nordic countries, Norway has the highest acceptance rate of patients above the age of 70, whereas dialysis is the preferred treatment for most of the elderly patients in the other Nordic countries. During the period 1989-93, death with a functioning kidney accounted for nearly half the graft losses in the Norwegian transplant population, and graft rejection for 37 percent. Cardiovascular disease was a predominant cause of death. PMID- 7997366 TI - [Pancreas transplantation in diabetes mellitus]. AB - In the course of 20-25 years' duration of disease, a large proportion of patients with type 1 (insulin-dependent) diabetes mellitus develop micro- and macro angiopathy and morphological organ changes. The development of late complications in diabetes is significantly correlated to the level of blood sugar regulation, and can be prevented or delayed by the establishment of stable normoglycaemia. A successful pancreas transplantation is today the sole means available for inducing stable normoglycaemia in patients with insulin deficiency. More than 5,000 pancreas transplantations have already been performed throughout the world, in most cases concomitantly with renal transplantation in patients with late stage diabetes. PMID- 7997367 TI - [Liver transplantation]. AB - Liver transplantation is performed in all the Nordic countries except Iceland. A Nordic action group with members from every centre draws up guidelines for organ exchange, treatment and research projects. The indications have been established, and results are steadily improving. The demand for organs is a manifest problem, particularly in acute cases where a new liver is required within a few days. After a successful transplantation, quality of life is comparable with that in the general population. PMID- 7997368 TI - [Heart transplantation in Scandinavia]. AB - Heart transplantation is well established therapy for end-stage heart failure, where no other treatment is available. From 1983 to the end of 1993, 620 heart transplantations were performed in the Nordic countries, the main causes of heart failure being dilated cardiomyopathy and ischaemic heart disease. The 1-year and 5-year actuarial survival rates were above 80 per cent and 70 per cent, respectively, which are higher than corresponding figures reported by the International Society of Heart and Lung Transplantation. The indications and contra-indications for heart transplantation, pre-operative evaluation and outcome are discussed in the article. PMID- 7997369 TI - [Lung transplantation]. AB - As alternative methods of lung transplantation are available, in terminal respiratory or combined cardio-respiratory failure, the surgical procedure can be chosen to suit the needs of the individual recipient in accordance with the philosophy of the transplant centre. At one Scandinavian centre the preferred procedure has been en bloc double lung transplantation with bronchial artery revascularisation, whereas at another centre the preference is for single lung transplantation if considered suitable in view of the pathology resulting in respiratory failure. Short-term results compare favourably with international registry standards. Problems commonly occurring in lung transplantation irrespective of the method, are reviewed in the article. PMID- 7997370 TI - [Xenograft]. AB - The ultimate purpose of research in xenografting (cross-species transplantation) is successful transplantation of tissue and organs from animals to human patients. Success in the clinical application of xenografting would mean an end to the shortage of donor organs. Xenografts are classified as concordant or discordant, depending on rejection factors and histology. Several clinical attempts have been made since 1963, but success has been limited. However, great progress has been made in laboratory attempts; and the procedures should now be given clinical trials. This success has been due to the efficacy of many of the newly developed immunosuppressive drugs. Discordant xenografting is still problematic, and in this type of transplantation the most promising approach would seem to be with isolated cells or cell clusters. PMID- 7997371 TI - [Priority setting in organ transplantation]. PMID- 7997372 TI - [Treatment of dyskinetic syndromes]. AB - Dyskinetic syndromes are conditions with involuntary movements. They can have different causes, but are often due to dysfunction of the basal ganglias. The clinical picture varies, but all show spontaneous alterations in intensity as well as deterioration with stress. This often leads to misjudgement of cases of dyskinesia. It is however important to be aware of these syndromes as medical treatment is effective in many cases. The treatment of tremor, tics, chorea, myoclonus, dystonia and medically induced dyskinesia is reviewed and the clinical pictures are briefly described. PMID- 7997373 TI - [Positron emission tomography and radiation exposure]. AB - With the ever increasing number of PET-systems in operation the associated problems of radiation protection gain increasing significance. Compared to "conventional" nuclear medicine there is a need for better shielding since the production of positron emitters also yields neutrons and secondary gamma radiation. Due to the short half-lives involved the radiochemistry has to handle high initial activities. Moreover the 511 keV energy of the positron-emitters results in the vicinity of the patient in a higher exposure rate than other nuclear medicine isotopes. For these reasons the typical effective dose to cyclotron personnel is about 2 mSv per year. The whole-body dose to the radiochemists is reported to be 0-20 microSv per charge, and to the medical personnel 10-50 microSv per application. The radiation exposures of the patients are comparable to those common in "conventional" nuclear medicine. PMID- 7997374 TI - [Radiation exposure from nuclear medicine studies in children]. AB - Nuclear medical examinations of children have to be performed with special regard to the problems of radiation protection because of the high radiation sensitivity esp. of infants and young children. The present contribution describes how any unnecessary radiation exposure can be avoided by the correct choice and planning of a nuclear medical study, by using the appropriate radiopharmaceutical as well as by the exact calculation of the amount of activity applied, depending on body surface resp. body weight of the child. A technically optimized method which employs the best technical equipment and personnel, being specially trained for working with children, are important conditions to achieve optimal results of nuclear medical tests. Due to the difficulties of direct dose measurements, large variations in the biokinetic behaviour of radiopharmaceuticals and the restriction to standard phantoms, individual dose calculations or dose estimations in pediatrics cause great problems. This is reflected by often large variations of dosimetrical data given in the literature. PMID- 7997375 TI - [Comparison of D2 receptor scintigraphy (123I-IBZM) with cerebral perfusion (99m Tc-HMPAO) in extrapyramidal disorders]. AB - The aim of this SPECT study was to determine whether there is a correlation between rCBF (99mTc-HMPAO) and D2 receptor binding (123I-IBZM) in disorders of the extrapyramidal system and in which situation the 99mTc-HMPAO scan could predict the outcome of the 123I-IBZM study. 13 patients with Parkinson's syndrome and 13 patients with hyperkinetic extrapyramidal disorders were studied. In all patients the two SPECT studies were performed within 2-7 days. ROIs were placed over the basal ganglia (BG), the frontal cortex (FC) and the cerebellum (CE). The ratios BG/FC and BG/CE were calculated. In both groups the scatter was lower when the frontal cortex was used as reference region. Among the patients with hyperkinetic extrapyramidal disorders the two patients with Huntington's chorea had lower rCBF and D2 receptor binding compared to other hyperkinetic extrapyramidal disorders. There was no correlation between D2 receptor binding and rCBF in the basal ganglia. The 99mTc-HMPAO studies did not provide clinically useful information, except in Huntington's chorea. PMID- 7997376 TI - [Preoperative evaluation of drug resistant focal epilepsies with 123I-iomazenil SPECT. Comparison with vidio/EEG monitoring and postoperative results]. AB - SPECT with the benzodiazepine receptor antagonist 123I-Iomazenil was performed in 33 patients with intractable partial seizures for pre-operative evaluation. The results combined with MRI and 99mTc-HMPAO-SPECT findings were compared with the video-assisted EEG monitoring ("gold standard") which localised the focus in 25 patients. 11 patients underwent surgical resection of the epileptogenic area and became seizure-free for a period up to 13 months. The Iomazenil SPECT had a significantly higher sensitivity compared to 99mTc-HMPAO in the visualization of an epileptogenic area and should be regularly used in the diagnostic of medically intractable partial seizures. PMID- 7997377 TI - 123I-IBZM SPECT: reconstruction methodology and results in parkinsonism and dystonia. AB - In 58 patients with Parkinsonism or dystonia striatal dopamine D2 receptors were investigated using 123I-iodobenzamide (123I-IBZM) single-photon emission computed tomography (SPECT). The influence of SPECT reconstruction methodology on semiquantification and the clinical value of 123I-IBZM SPECT were evaluated. Delineation of the striatal uptake and striatum/frontal cortex (ST/FC) ratios were improved by the use of compensation procedures for scatter and attenuation as well as the choice of an adequate filter. Satisfactory results were achieved using a Metz prefilter with a comparatively high order number (i.e. high cut-off and low suppression of higher frequencies via roll-off). Regarding clinical diagnoses it was not possible to differentiate between advanced idiopathic Parkinson's disease (IP) and Parkinsonism of other aetiology (OP) on the basis of 123I-IBZM SPECT. But patients with IP and favourable response to L-Dopa showed significantly higher ST/FC ratios than those with fluctuating response. In patients with dystonia ST/FC ratios were significantly higher compared to patients with IP or OP. PMID- 7997379 TI - Superselective radioembolization of hepatocellular carcinoma: 5-year results of a prospective study. AB - Twenty patients with unresectable hepatocellular carcinoma (HCC) were followed up to 5 years after transarterial radiotherapy with 90Y-resin particles. Diagnostic radioembolizations of 99mTc-macroaggregates facilitated scintigraphic assessment of activity distribution, dose evaluation and final procedural verification. The overall survival rates were 56, 38 and 14% (after 1, 2 and 3 years, resp.). Patients with unifocal HCC and a single feeding artery (n = 7) even presented 83, 67 and 40% (2 alive after 2.75 and 4 years). With multiple arteries (n = 7), the longest survival was 26 months. Patients with multifocal HCC survived up to 33 months after selective radioembolization. Quality of life was improved in all. Survival was positively correlated with absorbed dose but residual/recurrent tumour occurred even after > or = 300 Gy. Post-treatment symptoms were minimal (35 applications), pulmonary shunt rates were correctly predicted and pulmonary complications avoided. PMID- 7997378 TI - Functional MR mapping of activated cortical areas. AB - Magnetic resonance imaging (MRI) has recently been demonstrated to be sensitive to changes in neuronal activity of cortical areas. We report our initial experiences with functional MR brain mapping at high spatial resolution using a conventional whole-body MR system. A total of 10 visual and motor cortex activation studies were carried out on 8 healthy volunteers. In each examination, a time course series of 15 strongly T2*-weighted FLASH images was measured from three adjacent slices. The image analysis revealed a subtle but highly significant signal increase in cortical layers of gray matter in primary and associative visual as well as sensorimotoric cortex regions during periods of excessive brain activity provoked by photic stimuli or motoric tasks, respectively. To correlate brain structure and brain function, the computed MR brain activation maps were directly superimposed on T1-weighted anatomic spin echo images. With this advance into the area of functional neuroimaging, MRI is moving into an established domain of positron emission tomography (PET). We, therefore, discuss the advantages and limitations of the MR method in comparison to PET as far as this can be done at present. PMID- 7997380 TI - [Intra- and extrahepatic shunts in liver cirrhosis--evaluation by means of combined invasive nuclear medicine methods]. AB - The use of combined invasive nuclear medicine procedures allows the estimation of intra- and extrahepatic shunt volumes in patients with liver cirrhosis. The investigations were carried out after transhepatic portography and injection of 99mTc-MAA into the peripheral portal vein (hilum of the spleen) as well as into the central portal vein (hilum of the liver). A subtraction technique allowed the evaluation of shunt volumes (percentage). In 32 out of 36 patients an extra hepatic shunt volume of 29.2% (0%-84%) and an intra-hepatic shunt volume of 23.6% (0%-81%) was found. This technique may contribute to improving the results of shunt surgery. PMID- 7997381 TI - [Scintigraphy using 131I in oxyphilic carcinomas of the thyroid gland]. AB - The aim of the study was to ascertain the role of 131I scintigraphy (RIS) in the follow-up of oxyphilic thyroid carcinomas (OTC). It is discussed that metastases (M) and local recurrencies (LR) are incapable of accumulating 131I sufficiently; therefore, the usual strategy of RIS cannot be used for follow-up. The re examination of 91 patients suffering from OTC showed that 10/20 patients with M/LR did have a positive uptake of 131I, which could be used for therapy in 8 patients. An ablation of M using high-dose 131I therapy could be demonstrated in three younger patients who had cervical lymph node M 3 months after thyroidectomy as an early manifestation of their disease. In three patients RIS first led to the metastatic site. The clinical course of patients with distant M that developed at a later stage was unfavourable, even though they did accumulate 131I. Patients with positive uptake of 131I in M/LR were significantly younger (55a) than patients who had no uptake (67a) and belonged more often to stage I and II of UICC, namely 7/10 vs 2/10. RIS should be used especially in an early interval after thyroidectomy and individually for follow-up: as a diagnostic method and therapeutic instrument. PMID- 7997382 TI - Accumulation of 99mTc-glutathione in head and neck tumors. AB - Glutathione labelled with 99mTc was used to study blood clearance and normal distribution in 3 healthy volunteers and in 10 patients with biopsy-proven tumors in the head and neck region. Static scintigrams were obtained at 1, 3, 6, and 24 h. ROIs over tumors and normal soft tissues were compared to obtain T/N ratios. In normal subjects blood clearance reached a plateau at 6 h; no radio-activity accumulation in the head and neck region was observed. Only the cardiac blood pool, the liver, the kidneys and the urinary bladder were evident. Excretion was via the kidneys. Malignant tumors and metastases were well visualized in 7 patients (true-positive), starting at 1 h. The mean T/N ratio was 2.69 +/- 0.77. The best images were obtained at 3-6 h. 1 false-positive (granulamatous reaction), 1 false-negative (malignant epithelial tumor in the radix of tongue) and 1 true-negative (angiofibroma) results were obtained. 99mTc-GSH is a potential radiopharmaceutical for the scintigraphic visualization of head and neck tumors. Further clinical studies are warranted to show its sensitivity and accuracy. PMID- 7997383 TI - [Peripheral quantitative computer tomography compared with other bone density measurements]. PMID- 7997384 TI - Effect of simultaneous didanosine administration on itraconazole absorption in healthy volunteers. AB - STUDY OBJECTIVE: To investigate the effect of simultaneously administered didanosine (ddI) on the absorption of a single dose of itraconazole. DESIGN: Randomized, crossover, unblinded single-dose pharmacokinetic study in healthy volunteers. Comparisons of itraconazole alone and itraconazole with simultaneous ddI were performed on days 1 and 15. SETTING: A university medical center. PATIENTS: Seven healthy men and women. Six subjects (86%) completed the study; one was removed due to the development of a rash. INTERVENTIONS: Volunteers received a single 200-mg oral dose of itraconazole or itraconazole with concomitant oral ddI 300 mg (two 150-mg tablets) dispersed in 240 ml water. Each regimen was separated by a 2-week washout period. Serum samples were obtained frequently for 12 hours after the dose. MEASUREMENTS AND MAIN RESULTS: Concentrations of itraconazole were determined using a microbiologic assay. Individual concentrations in serum versus time data were evaluated by linear regression analysis. Peak serum concentration and time to peak were determined by visual inspection of each individual's serum concentration-time curve. A mean +/- SD peak serum itraconazole concentration of 0.90 +/- 0.30 micrograms/ml was observed at 3.0 +/- 0.7 hours when itraconazole was administered alone, compared with undetectable levels in all patients during therapy with ddI. CONCLUSIONS: Simultaneous oral administration of ddI significantly decreases absorption of itraconazole. These drugs should not be administered concurrently. PMID- 7997385 TI - Oral torsemide in patients with chronic congestive heart failure: effects on body weight, edema, and electrolyte excretion. Torsemide Investigators Group. AB - STUDY OBJECTIVE: To assess the effects of torsemide on the primary end point of change in body weight from baseline, and the following secondary end points: urinary sodium, potassium, and chloride excretion, and urine volume after the first dose of drug. DESIGN: Randomized, parallel, double-blind, multicenter study in patients treated with torsemide 5 mg (n = 19), 10 mg (n = 18), or 20 mg (n = 14), or placebo (n = 15) for 7 days. PATIENTS: Sixty-six patients with New York Heart Association class II or III congestive heart failure and edema. RESULTS: At the end of the study, patients treated with torsemide 10 and 20 mg demonstrated a significant reduction in body weight compared with those receiving placebo (-1.62 and -1.30 kg, respectively), and those treated with torsemide 5 mg did not (-0.60 kg). The severity of edema decreased with increasing torsemide dose. Torsemide caused no greater frequency of adverse effects with increasing dose. CONCLUSION: Orally administered torsemide 5, 10, and 20 mg once/day for 7 days were well tolerated. Doses of 10 and 20 mg were effective in producing weight loss. PMID- 7997386 TI - Effect of intravenous fructose-1,6-diphosphate on myocardial contractility in patients with left ventricular dysfunction. AB - STUDY OBJECTIVE: To examine the effects of fructose-1,6-diphosphate on myocardial performance using nuclear scintigraphy. DESIGN: Prospective, randomized, single blind, parallel study. SETTING: Urban teaching hospital clinical research center. PATIENTS: Individuals with New York Heart Association functional class II-III heart failure (mild to moderate). INTERVENTIONS: Subjects received either intravenous fructose-1,6-diphosphate 125 mg/kg or normal saline 1.3 ml/kg every 12 hours over 10 minutes for four consecutive doses. Left ventricular performance was assessed by radionuclide ventriculography at baseline and within 60 minutes after the fourth infusion. Vital signs were monitored throughout the study period. MEASUREMENTS AND MAIN RESULTS: Fructose-1,6-diphosphate resulted in a modest 7% increase in left ventricular ejection fraction (p < 0.05). Peak ejection rate and peak diastolic filling rate did not change significantly. There were no changes in blood pressure or heart rate with either fructose-1,6 diphosphate or placebo. CONCLUSIONS: Fructose-1,6-diphosphate produces a modest but significant increase in left ventricular ejection fraction in patients with mild to moderate heart failure. PMID- 7997387 TI - Genital herpes simplex infections in patients with the acquired immunodeficiency syndrome. AB - On August 14, 1987, the Centers for Disease Control revised the surveillance case definition for the acquired immunodeficiency syndrome (AIDS) to include several indicator diseases. The addition of herpes simplex virus (HSV) infections to the definition reemphasized the increasing frequency of severe HSV infections in patients also infected with the human immunodeficiency virus (HIV). These infections in patients with AIDS are associated with considerable morbidity similar to reports of HSV in other immunocompromised populations. Their spectrum can include persistent or recurrent genital disease, severe visceral involvement, and disseminated infection. Patients with AIDS also are at increased risk of drug toxicities when receiving treatment for HSV infections in addition to antiretroviral therapy. Acyclovir, a selective and specific inhibitor of HSV replication, has been the mainstay of safe and effective treatment for HSV for more than a decade. However, reports of acyclovir-resistant strains of HSV in patients with AIDS have been steadily increasing since 1989. Although foscarnet has been successful in treating acyclovir-resistant strains, foscarnet-resistant strains have also been isolated. The search to find novel approaches for the treatment and suppression of HSV in patients with AIDS has become an added challenge in the management of this devastating disease. PMID- 7997388 TI - Treatment of acute neuroleptic-induced movement disorders. AB - Acute extrapyramidal syndromes (EPS), including dystonia, parkinsonism, and akathisia, are associated with the use of virtually all neuroleptic agents. They may be alleviated by reducing the neuroleptic dosage, switching to a lower potency drug, or administering an adjunctive agent such as an anticholinergic, amantadine, benzodiazepine, or beta-blocker. Akathisia may be only partly dispelled by anticholinergics; alternatives are beta-blockers, benzodiazepines, and clonidine. In patients receiving long-term neuroleptic therapy, both the prophylactic use and the duration of treatment with concomitant anti-EPS drugs are controversial. Administration of prophylactic anti-EPS drugs should be based on the likelihood that the patient will develop EPS, as well as the risk of adverse reactions resulting from extended use of the agents in a specific patient. The decision to continue anti-EPS therapy should be reevaluated frequently, especially in elderly patients. PMID- 7997389 TI - Drug-induced lichen planus. AB - Lichen planus is a relatively common skin disorder of unknown etiology. A wide variety of drugs have been implicated in its cause. Using five or more cases of drug-induced lichen planus reported in at least three separate reports with at least one case of probable cause by the scale of Naranjo et al as criteria, sufficient evidence exists that beta-blockers, methyldopa, penicillamine, quinidine, and quinine play a role in this disorder. Evidence is insufficient for angiotensin-converting enzyme inhibitors, sulfonylurea agents, carbamazepine, gold, lithium, and a host of miscellaneous drugs. Given available epidemiologic evidence, nonsteroidal antiinflammatory agents probably should also be considered causative. Differentiating drug-induced lichen planus from the idiopathic disorder is difficult; most evidence is based on the dechallenge and rechallenge with the drug when these data are available. PMID- 7997391 TI - A prospective evaluation of benzodiazepine guidelines in the management of patients hospitalized for alcohol withdrawal. AB - Our institution adopted guidelines for the selection of benzodiazepines to be administered to patients hospitalized for alcohol withdrawal. We assessed the guidelines' impact on prescribing habits, benzodiazepine dosage requirements and costs, and length of intensive care unit (ICU) stay. A 6-month prospective, observational study was performed in 50 patients who exhibited signs of alcohol withdrawal and received benzodiazepine therapy. Appropriate therapy was defined as lorazepam for patients 60 years and older or those with hepatic dysfunction, and chlordiazepoxide for all other patients. Benzodiazepine costs were calculated based on acquisition cost. Based on our guidelines, 76% of patients were appropriate candidates for a long-acting agent such as chlordiazepoxide; 61% of these candidates actually received such a drug. Using a benzodiazepine conversion to compare doses in chlordiazepoxide equivalents, there was a significant difference in the total mean dose of chlordiazepoxide (1295.5 mg, SD +/- 1571) compared with lorazepam (365.5 mg; SD +/- 446) (p < 0.01). The mean total chlordiazepoxide acquisition cost was $61.74 (range $0.03-585.98) per patient (28 patients); prior to adoption of the guidelines, the mean cost of benzodiazepine therapy was $1008.72 (+/- $1554.45). For patients receiving chlordiazepoxide, the mean days of ICU and hospital stay were 1.1 days (range 0-9 days) and 5.6 days (range 1-17 days), respectively; before adoption of the guidelines, the mean number of days of ICU stay was significantly greater (4.1 days, p < 0.0001). The guidelines resulted in a substantial change in benzodiazepine prescribing patterns.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7997390 TI - A retrospective review and assessment of benzodiazepines in the treatment of alcohol withdrawal in hospitalized patients. AB - Little information has been published concerning differences among the benzodiazepines in treating hospitalized patients with severe symptoms of alcohol withdrawal. We attempted to determine the length and type of hospital stay, and the pattern and appropriateness of administration, dosage requirements, and costs associated with benzodiazepines in patients undergoing alcohol withdrawal. A 1 year retrospective analysis was performed for 57 hospitalized patients. Appropriate therapy was defined as lorazepam for patients 60 years and older or those with hepatic dysfunction, and chlordiazepoxide or diazepam for all other patients. Drug costs were calculated based on acquisition costs. The mean number of days of benzodiazepine treatment and length of stay in the intensive care unit (ICU) were 6.2 days (range 1-30 days) and 3.9 days (range 0-12 day), respectively. Fifty-six patients were admitted to the ICU for management or for monitoring continuous-infusion lorazepam; one patient received chlordiazepoxide on a general ward. Total mean lorazepam infusion required per patient was 324 mg (range 2-5956 mg). The total benzodiazepine acquisition cost was $56,489 (mean $1009, range $0.06-7157/patient). The total costs of benzodiazepine acquisition and ICU charge were $404,346 (mean $7462/patient). Based on our criteria, 41 of 57 patients could have been treated appropriately with chlordiazepoxide, which would have resulted in an estimated drug-acquisition cost savings of at least $37,000. Mean benzodiazepine dosage requirements in patients hospitalized for alcohol withdrawal appear higher than previously reported. Approximately 70% of our patients were not of advanced age and had no evidence of organ dysfunction, and therefore, could have been treated with an oxidized benzodiazepine (i.e., chlordiazepoxide).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7997392 TI - Retrospective analysis of postoperative nausea and vomiting to determine antiemetic activity of droperidol added to propofol: a possible drug interaction. AB - Propofol decreases the frequency of postoperative nausea and vomiting. We investigated whether its antiemetic activity could be improved further by coadministration of droperidol. We retrospectively reviewed the records of 266 women who underwent laparoscopic operations with nitrous oxide anesthesia and thiopental or propofol induction. The records were screened for frequency and time of occurrence of nausea and vomiting, concurrent drug use, duration of surgery, and times of recovery room admission and discharge. The combination of droperidol and thiopental decreased the frequency of nausea and vomiting over droperidol plus propofol, propofol alone, and thiopental alone. The addition of droperidol to propofol anesthesia doubled the frequency of multiple nausea and vomiting episodes, suggesting a possible interaction between the drugs. We cannot recommend that droperidol be added to propofol anesthesia for prophylaxis of postoperative nausea and vomiting. PMID- 7997393 TI - Effects of long-term drugs on alfentanil clearance in patients undergoing renal transplantation. AB - Although patients in renal failure frequently take several drugs on a long-term basis, drug-induced alterations in alfentanil metabolism have not been examined as a possible source of variability in alfentanil clearance in this population. We compared the pharmacokinetics of alfentanil during renal transplantation in seven patients receiving and six not receiving long-term drug therapy. After the rapid intravenous injection of alfentanil 100 micrograms/kg during isoflurane anesthesia, plasma concentrations were measured at intervals up to 6 hours by radioimmunoassay. The terminal elimination half-life, steady-state volume of distribution (Vdss), and total body clearance were determined by noncompartmental methods. There was no statistical difference in the Vdss between the two patient groups. However, clearance was significantly higher and elimination half-life lower in the group taking long-term drugs: clearance 6.94 +/- 4.64 versus 3.47 +/ 0.16 ml.kg-1.min-1, and elimination half-life 50.6 +/- 13.9 versus 90.7 +/- 22.4 minutes, respectively (p < 0.05). The higher clearance occurred even though five of the seven patients were taking agents known to be metabolized by the same cytochrome P-450 hepatic isozyme that metabolizes alfentanil and therefore potential competitive inhibitors of alfentanil metabolism. Drugs taken by the three patients with the highest alfentanil clearances included known inducers of hepatic drug metabolism. Thus, in the presence of several long-term drugs, the clearance of alfentanil appears to be noticeably increased by inducers of hepatic drug metabolism but unaffected by potential competitive inhibitors. PMID- 7997394 TI - Effects of long-term oral carvedilol on the steady-state pharmacokinetics of oral digoxin in patients with mild to moderate hypertension. AB - The effect of multiple oral doses of carvedilol on steady-state plasma digoxin pharmacokinetics was evaluated in 12 patients with mild to moderate hypertension. Area under the curve (AUC), mean maximum plasma concentration (Cmax), mean time to maximum concentration (Tmax), concentration at 24 hours after the dose (C24), creatinine clearance, renal digoxin clearance, and urinary digoxin excretion were determined after patients took oral digoxin 0.25 mg once/day for 2 weeks. Carvedilol was added to the regimen, and digoxin pharmacokinetics were assessed after 2 weeks of concurrent treatment. The AUC and Cmax for digoxin increased by 14% and 32%, respectively (p < 0.05), with no change in Tmax. The 24-hour urinary digoxin excretion and 24-hour renal digoxin clearance increased by 45% and 26%, respectively (p < 0.05), with no change in creatinine clearance. Carvedilol appears to increase digoxin's oral bioavailability as well as renal elimination. The absolute change in digoxin pharmacokinetics was small and not clinically significant. The significance of the interaction in other patient populations remains to be studied. PMID- 7997395 TI - Disposition of tablet and capsule formulations of digoxin in the elderly. AB - STUDY OBJECTIVE: To compare digoxin tablets and liquid-filled capsules with respect to excretion of the drug and its metabolites in urine and feces at steady state. DESIGN: A randomized, crossover trial, each period lasting 3 weeks, with no washout period. SETTING: A university hospital. PATIENTS: Six patients, five of whom were elderly, with histories of gastrointestinal disorders, such as hypochlorhydria, intestinal bacterial overgrowth, and inflammatory bowel disease. INTERVENTIONS: The patients received digoxin once/day in either tablet or capsule form for 3 weeks, and then were switched to the other formulation. Total urinary and fecal excretion from the last 3 days of each regimen were analyzed for the drug and metabolites. MEASUREMENTS AND MAIN RESULTS: No statistically significant differences were found between tablets and capsules in recovery of digoxin or its metabolites in urine or feces (p = 0.05). One subject had a 4-fold increase in urinary drug excretion and 50% decrease in fecal excretion after taking the capsules compared with tablets. Intersubject variability in extent and type of metabolite excretion was greater than intrasubject variability. CONCLUSIONS: Fecal analyses may be an accurate way to classify patients as formers of digoxin reduction products. PMID- 7997396 TI - Subcapsular hematoma after laparoscopic cholecystectomy, associated with ketorolac administration. AB - Ketorolac is the first injectable nonsteroidal antiinflammatory drug used as an analgesic in the perioperative period. Its adverse effect profile is different from that of the opioid analgesics; in particular, in its lack of respiratory depressive actions. However, ketorolac has risks associated with its perioperative administration, including episodes of substantial gastrointestinal bleeding. A patient undergoing elective laparoscopic cholecystectomy developed a subcapsular hepatic hematoma shortly after receiving a dose of injectable ketorolac. No evidence of parenchymal injury was found on laparoscopy, which argues against iatrogenic trauma. Clinicians should be aware that ketorolac may cause or aggravate bleeding, and it should be used with caution in perioperative patients. PMID- 7997397 TI - Thrombolytic therapy for pulmonary embolism: reversal of shock in the early postoperative period. AB - Life-threatening acute pulmonary embolism (PE) associated with circulatory shock requires effective therapy directed at removing the obstruction to flow in the pulmonary vasculature and improving hemodynamics. Options for treatment are pulmonary embolectomy and thrombolytic therapy. Although safe and effective, thrombolytic therapy is relatively contraindicated within 10 days of major surgery due to the risk of bleeding. Intravenous streptokinase was administered to a man on the third postoperative day for treatment of a massive PE associated with circulatory shock. Within 2 hours of initiating therapy, the patient experienced marked improvement in hemodynamics and tissue perfusion. No bleeding complications were noted. This case demonstrates that intravenous thrombolytics may be administered safely to patients who have recently undergone surgery. It also underscores that the decision to apply the therapy when relatively contraindicated must be made on an individual patient basis and thus ensure that potentially life-saving therapy is not withheld from those who require it most. PMID- 7997398 TI - Hospital and pharmacy characteristics associated with mortality rates in United States hospitals. AB - We attempted to determine hospital and pharmacy characteristics associated with mortality rates in 4864 United States hospitals. Data were obtained from the Health Care Financing Administration, the American Hospital Association, and the National Clinical Pharmacy Services survey. Univariate and multivariate regression models were used to determine which hospital characteristics were associated with mortality. A similar regression analysis was performed on 718 hospitals for which detailed pharmacy information was available. In a multivariate regression model, some characteristics of 4864 hospitals associated with reduced mortality rates were high-technology index (R2 = 0.09, p < 0.001), severity of illness (R2 = 0.048, p < 0.001), number of hospital beds (R2 = 0.016, p < 0.001), and medical personnel (R2 = 0.012, p < 0.001). This analysis accounted for 41% of the mortality rate variance. For the 718 hospitals and pharmacies, some of these characteristics were high-technology index (R2 = 0.157, p < 0.001), severity of illness (R2 = 0.07, p < 0.001), number of pharmacists/average daily census (R2 = 0.021, p < 0.001), and combined hospitalwide clinical pharmacy services (R2 = 0.016, p < 0.01). The results of this analysis were similar to those in the only other large study in this area, but that excluded pharmacy characteristics. This is the first study to show a statistically significant association between pharmacist and pharmacy variables and reduced hospital mortality rates. PMID- 7997399 TI - A personal suggestion for health care reform. PMID- 7997400 TI - Exposure to passive smoking during pregnancy and childhood, and cancer risk: the epidemiological evidence. AB - There are relatively few studies on the association between environmental tobacco smoke (ETS) during pregnancy and childhood, and cancer in childhood, adolescence or adulthood. The associations between maternal smoking during pregnancy and childhood cancer have been studied intensively, but there is no clear association overall, or for specific sites. The association between childhood cancer and smoking by the father in the preconceptional period, and by either parent during the child's lifetime, has been little studied. Again, no clear associations have been identified. However, evidence from studies of exposure to known carcinogens from ETS, and of genotoxic effects indicates that any effect, if present, is expected to be weak, and therefore could not have been detected by most of the studies which have been performed, due to the small number of cases included. There is some consistency of association between ETS exposure in childhood and the risk of lung cancers in adulthood. There is therefore a need for further epidemiological studies on ETS exposure during pregnancy and childhood and the occurrence of cancers. PMID- 7997401 TI - Birthweight-specific mortality rates--are they meaningful? PMID- 7997402 TI - Fumes from the spleen. PMID- 7997403 TI - Secular trends of sudden infant death syndrome in Norway 1967-1988: application of a method of case identification to Norwegian registry data. AB - In Norway, towards the end of the 1980s, sudden infant death syndrome (SIDS) was the most frequent cause of infant death. Both SIDS and the total post-perinatal mortality rates had increased. This paper presents a procedure for identifying SIDS from death certificates. Supplemented with additional information, a database was established to evaluate secular trends of SIDS and for further analytical research. The Medical Birth Registry of Norway comprises 1.3 million births from 1967 to 1988. Of these, 5447 infants died in the post-perinatal period. The cause of death was reviewed by an expert panel and 1984 cases of SIDS were retrieved. Low maternal age, higher birth order, male gender, and lower birth-weight were confirmed as risk factors for SIDS. In 1988, the rate for SIDS and for total post-perinatal deaths reached 2.69 and 5.02 per 1000 infants at risk. The incidence of SIDS increased 2.2 times from the period 1967-1971 to the period 1987-1988. Adjusted for maternal age, birth order, and birthweight, the odds ratio was 3.1. The increase is due to factors not yet accounted for. Adjusted mortality rates for the other post-perinatal deaths were not different from the crude rates. PMID- 7997404 TI - Thirty years of retinoblastoma (1960-89): changing patterns of incidence. AB - This study of a 30-year population-based dataset investigates further an earlier observation that the incidence of sporadic bilateral retinoblastoma appeared to be increasing in recent years in the West Midlands Health Authority Region (WMHAR). Stringent measures were applied to ensure complete ascertainment of all cases of retinoblastoma in children in the region, resulting in a total of 117 cases diagnosed during the period 1960-89 in the WMHAR. Hospital case notes were abstracted and follow-up data obtained. Incidence rates were calculated. The overall incidence remained constant over the 30-year period, but that of sporadic bilateral tumours increased, with a corresponding decline in familial cases. There was a statistically significant excess seen in Asian children. PMID- 7997405 TI - Meconium staining of the liquor in a low-risk population. AB - Although the significance of meconium-stained amniotic fluid as a sign of fetal distress remains controversial, its presence remains a concern to both obstetricians and neonatologists since signs of asphyxia and meconium staining are associated with an increase in perinatal morbidity and mortality. The aim of this study was to evaluate the role of meconium staining of the liquor in the low risk obstetric population in terms of fetal distress and perinatal morbidity and mortality. In a prospective cohort study at a referral hospital and at one of two municipal clinics, women with a singleton pregnancy of 37 to 42 weeks gestation and with no pre-defined risk factor were recruited into the study. Study patients comprised those with meconium staining of the liquor and controls comprised similar women but with clear liquor. Meconium staining of the liquor was associated with poor outcome in all the outcome measures assessed. Fetal heart rate (FHR) abnormality was more closely associated with adverse outcome than meconium staining, and thin meconium alone was not associated with any adverse outcome except respiratory distress. Women with thin meconium in the presence of normal FHR can therefore be safely managed at the clinic level. Thick meconium itself was a risk factor for poor outcome, more so if associated with FHR abnormality, and should be an indicator for early referral. PMID- 7997406 TI - Infant feeding and growth of Chinese infants: birth to 2 years. AB - A cohort of 174 healthy full-term Chinese infants was followed up regularly for 2 years for their weight, length, head circumference, triceps and subscapular skinfold thickness, and their feeding practice. The majority of babies (92% at 2 months) were bottle fed with full strength infant formula. The energy intake over the first year of life was comparable with that of healthy Caucasian infants. The mean protein intake during the weaning period exceeded fourfold that of the WHO recommendation. At 2 years, infants were -0.6 standard deviation score (SDS) lighter and -0.4 SDS shorter than the National Centre for Health Statistics (NCHS) reference. PMID- 7997407 TI - Electric iron contact burns in an Australian paediatric population. AB - Accidental burn injury is common among children. Contact burns are the second most frequent cause of burns in children and electric iron contact burns constitute a substantial proportion of this group. A prospective analysis of electric iron burns presenting from 1988 to 1991 was conducted. The 38 iron burns treated during this period represented 19% of contact burns treated. The mean age of injury was 19 months. The male to female ratio was 1.1:1 and 80% involved the upper limb. Twenty-five per cent required operation. All burns occurred in the child's own home with the majority (74%) occurring in the central living areas while the child was supervised (45%). The child was most likely to be injured by touching the iron directly or pulling the cord. A substantial number of burns occurred even after the iron was switched off. Education should be directed towards the caregivers of young children emphasizing the need to use and store irons in areas to which children do not have free access. Powerpoints should be placed so that children cannot reach the cord. Manufacturers should provide insulated pads in which to store the iron and a retracting cord to help prevent the cord being within a child's reach. PMID- 7997408 TI - Infants with single umbilical artery studied in a national registry. 3: A case control study of risk factors. AB - This case control study reports associations between single umbilical artery (SUA) in newborns and some maternal biological characteristics. The study is based on chromosomally normal singleton infants born in Sweden between 1983 and 1990. Information on the maternal characteristics studied was obtained prospectively. There were 2920 cases identified and 5840 controls were selected. An association was found with: previous perinatal death, retained placenta, placenta praevia, maternal diabetes, epilepsy and hydramnios. Increased odds ratios were seen also for spontaneous abortion and abruptio placentae but did not reach statistical significance. No association was found with previous induced abortion, involuntary childlessness, or the use of contraceptives after the last menstrual period. PMID- 7997409 TI - Survival of infants with neural tube defects in Western Australia 1966-1990. AB - To investigate the survival of infants with neural tube defects in Western Australia from 1966 to 1990, cases of neural tube defects were ascertained from multiple sources. Survival of infants with anencephaly, spina bifida, and encephalocoele was examined separately, and four birth cohorts were compared: 1966-1972 (when most surviving infants were actively treated), 1973-1979 (a period of stringent application of selection criteria for treatment), 1980-1985 (some relaxation of selection criteria), and 1986-1990 (further relaxation of selection criteria). There was an increase in terminations of pregnancies affected with anencephaly over the study period, and a fall in the proportion of both liveborn and stillborn infants with anencephaly. Most liveborn infants (76.4%) died in the first 24 hours, and none survived longer than 5 days. Most infants with encephalocoele (76.4%) were liveborn, and survival was poorest in the 1973-1979 cohort, although the difference in survival across cohorts just failed to attain a formal level of significance. For spina bifida, there was an increase in terminations of affected pregnancies over the study period. Survival of liveborn infants with spina bifida was poorest in the 1973-1979 cohort, and greatest in the most recent cohort. These improvements in survival are likely to be the result of relaxation of selection criteria for treatment, improvements in treatment and, to a lesser extent, selective termination of affected pregnancies. PMID- 7997410 TI - Aortic valve injury 10 years after tetralogy of Fallot repair. AB - Although recognized by pediatric cardiac surgeons, aortic insufficiency as a technical complication after tetralogy of Fallot repair is poorly documented, especially if it occurs late. The case of a boy with aortic insufficiency 10 years after complete tetralogy repair is described. No documentation in the literature other than summary statements in textbooks of this occurrence was found. PMID- 7997412 TI - Spontaneous pneumopericardium in a teenager. PMID- 7997411 TI - Massive cardiac tumor presenting as severe cyanosis in a newborn. PMID- 7997413 TI - Boy:girl ratio in children born with different forms of cardiac malformation: a population-based study. AB - The boy:girl ratio was calculated for all live births with cardiac malformation in Bohemia (population 6.3 million) from 1977-1984. Complete coverage of all deceased children in Bohemia by necropsy and of all patients with heart disease by our center enabled us to collect reliable data. Of 4409 children born with a heart defect, there were 2296 boys and 2113 girls, a ratio of 1.09:1. In the total population of 664,218 children born during the same period of time, the ratio was 1.06:1. A higher proportion of boys was found with double outlet right ventricle (2.68:1), hypoplastic left heart (2.25:1), transposition of the great arteries (2.11:1), aortic stenosis (1.95:1), pulmonary atresia (1.55:1), tricuspid atresia (1.45:1), coarctation of the aorta (1.30:1), and corrected transposition of the great arteries (1.25:1). There were significantly more girls than boys with persistent ductus arteriosus (1:1.66), Ebstein's anomaly of the tricuspid valve (1:1.57), truncus arteriosus (1:1.22), atrioventricular septal defect (1:1.17), and tetralogy of Fallot (1:1.12). The difference in sex prevalence in the remaining heart defects was less than 10%. PMID- 7997414 TI - Follow-up of surgical correction of vascular anomalies causing tracheobronchial compression. AB - Between January 1977 and January 1990, 44 patients with symptomatic vascular rings/slings required surgical intervention at this center. Nineteen patients had double aortic arch (group I); 13 patients had vascular ring consisting of right aortic arch, anomalous origin of the left subclavian artery, and ligamentum arteriosus (group II); eight patients had innominate artery compression (group III); and four patients had pulmonary artery sling (group IV). Three patients had complex congenital heart defect and died secondary to it and are excluded from the study. Follow-up was obtained on 31 patients (76%). The follow-up period ranged from 0.4 years to 10.9 years, with a mean of 3.6 years. Seventy percent of the overall group were asymptomatic, and 30% of patients continued to have upper and lower respiratory symptoms on late follow-up. One third of patients in groups I and II, who underwent surgical repair, continue to have symptoms. Patients who have persistent symptoms should be further evaluated with PFTs, MRI, and bronchoscopy, and may benefit from aortopexy. Patients with innominate artery compression and pulmonary artery sling do well soon after surgery with relief of most of their symptoms. PMID- 7997415 TI - Double-blind placebo-controlled trial of corticosteroids in children with postpericardiotomy syndrome. AB - The objective of this study was to assess the efficacy of corticosteroids in hastening the recovery of children with postpericardiotomy syndrome, using a randomized double-blind placebo-controlled trial in a tertiary care referral center for pediatric cardiology and cardiac surgery. Twenty-one children, 6 months of age or older (mean age 3.9 years) with postpericardiotomy syndrome following open or closed heart surgery were administered either prednisone 2 mg/kg/day reducing to zero over 14 days (n = 12) or placebo (n = 9). Progress was monitored by daily clinical assessment and alternate day cross-sectional echocardiograms. The primary measures of efficacy were the number of patients in remission at 72 h and at 1 week. No difference in remission rates were found at 72 h, but at 1 week significantly more children treated with prednisone were in remission (placebo 3/9; prednisone 10/12, p = 0.03). A trend to faster resolution of all symptoms and signs was seen in the prednisone-treated group but this was not associated with earlier hospital discharge. Enlargement of pericardial effusion was seen in two children treated with steroids. No complications of treatment were encountered. Prednisone hastens the recovery of children with postopericardiotomy syndrome. Pericardial effusions may increase in size despite the use of corticosteroids. PMID- 7997417 TI - Pulmonary vasculature changes associated with idiopathic closure of the ductus arteriosus and hydrops fetalis. AB - Antenatal closure of the ductus arteriosus has been considered as a potential risk factor for the development of hydrops fetalis and persistent fetal circulation of the newborn. We present an infant with antenatal ductal closure who had not received prenatal prostaglandin synthetase inhibitors. The pulmonary vascular morphological findings are described and compared to three additional infants in whom the ductus arteriosus was known to be patent; one with neonatal sepsis and two others with hydrops fetalis. The infants with fetal hydrops, regardless of etiology, had increased muscularization of the acinar pulmonary arteries. In addition, the infant with antenatal closure of the ductus arteriosus also had both a significant decrease in preacinar arterial external diameter and an increase in medial wall thickness. Antenatal closure of the ductus arteriosus appears to enhance in utero pulmonary blood flow and this may be the cause of pulmonary vascular remodeling. PMID- 7997416 TI - Effects of pentoxifylline (Trental) on blood flow, viscosity, and oxygen transport in young adults with inoperable cyanotic congenital heart disease. AB - Four polycythemic young adults with inoperable cyanotic congenital heart disease were treated for 12 weeks with 20 mg/kg/day of pentoxifylline in an attempt to increase pulmonary blood flow by improving red blood cell demorability and decreasing whole blood viscosity. Treatment caused a rise in mean arterial oxygen saturation from 75-82%, a fall in the mean oxygen extraction coefficient from 47 40%, and a fall in mean oxygen consumption from 186-169 ml/min/m2. Pentoxifylline decreased whole blood, but not plasma, viscosity at all hematocrits over a range of shear rates. Two patients had significant bleeding episodes during treatment. PMID- 7997418 TI - Per-catheter creation of ASD. PMID- 7997419 TI - Response to prostaglandin E1 in neonates with intracranial arteriovenous malformation treated for suspected congenital heart disease. AB - Two neonates with cardiovascular symptoms associated with intracranial AVM were initially considered to have ductal-dependent congenital heart disease. Prostaglandin E1 (PGE1) infusion, initiated to achieve patency of the ductus arteriosus, produced improved oxygenation and cardiovascular status in both infants. Other vascular effects of PGE1, including pulmonary and extracranial systemic vasodilation, likely accounted for these unique observations in the infants with intracranial AVM. Not only may the signs and symptoms of congenital heart disease be imitated by intracranial AVM, but improved oxygenation and cardiovascular status with PGE1 infusion used for suspected congenital heart disease may be observed as well. PMID- 7997420 TI - Echocardiographic images in unusual hemorrhagic pericarditis. AB - Two children with acute symptomatic pericardial effusion had unusual echocardiographic findings. In each case, the pericardial effusion was hemorrhagic. Echocardiography displayed numerous linear bands coursing across the pericardial space. Recognition of this characteristic image may predict that an acute effusion is loculated, and perhaps hemorrhagic, so that surgical drainage will offer the most definitive treatment. Knowledge gained during management of the first patient was used to anticipate treatment of the second patient, influencing the choice to perform pericardiocentesis in the catheterization laboratory and to alert surgical colleagues of the anticipated need for surgical drainage. PMID- 7997421 TI - Dilated cardiomyopathy with 3-methylglutaconic aciduria. AB - The case of an infant with both dilated cardiomyopathy and 3-methylglutaconic aciduria is presented. The literature on this subject is reviewed. PMID- 7997422 TI - Discrete subaortic stenosis after successful treatment of congenital aortic valve stenosis. AB - Two cases of discrete subaortic obstruction which developed in a previously normal left ventricular outflow tract of patients with congenital valvar aortic stenosis are described. These examples emphasize the need for careful scrutiny of the etiology of recurrent postoperative left ventricular outflow tract obstruction. PMID- 7997423 TI - Progressive pulmonary venous obstruction and pulmonary interstitial fibrosis associated with tetralogy of Fallot. AB - Stenosis of individual pulmonary veins is a rare condition associated with a very high mortality. The present report is the first known case of progressive pulmonary venous obstruction associated with the tetralogy of Fallot. This clinical and anatomical study suggests that initial dynamic and possibly reversible occlusion occurs at the junction of the pulmonary vein and left atrium. Anatomical lesions in pulmonary veins then develop, possibly secondary to functional stenosis. The usually fatal outcome of these cases is due to the development of fixed pulmonary venous occlusion and possibly pulmonary interstitial fibrosis. The rapid progression of pulmonary venous stenosis strongly suggests that discrete veno-atrial stenosis should be surgically corrected as early as possible to prevent the irreversible diffuse pulmonary venous obstruction associated with an invariably fatal prognosis. PMID- 7997425 TI - Color Doppler flow mapping of the patent ductus arteriosus in very low birthweight neonates: echocardiographic and clinical findings. AB - Forty-eight preterm infants (mean birthweight 1.0 +/- 0.3 kg; mean gestational age 28 +/- 3 weeks) underwent serial echocardiograms and physical examinations in order to determine the correlation between color Doppler flow mapping (CDFM) results and physical findings of a patent ductus arteriosus (PDA), the predictive value of early CDFM as an indicator of subsequent requirement for treatment of a PDA, and to determine the direction and duration of ductal shunting and the rate of ductal closure and opening. CDFM analysis and cardiac physical examination of left-to-right ductal shunting were usually concordant in infants with a large PDA shunt, the most reliable physical finding being increased precordial activity. CDFM studies on day 2 or 3 of postnatal life had prognostic value with regard to subsequent need for closing the PDA. Additional findings included the absence of right-to-left PDA shunting in infants < 1 kg and < 28 weeks gestation and the absence of ductal reopening in infants in whom it had closed spontaneously. After complete PDA closure using indomethacin, subsequent ductal reopening is uncommon, except in infants < 25 weeks gestation and < 700 g bodyweight. PMID- 7997424 TI - Cardiac function in healthy infants and children: Doppler echocardiographic evaluation. AB - To establish normal values for Doppler-derived parameters of cardiac function, pulsed-wave Doppler recordings from the ascending aorta were obtained in 80 healthy infants and children. Stroke and minute distance, peak velocity, mean acceleration, acceleration and ejection time intervals, and the acceleration/ejection time ratios were measured or calculated from the Doppler recordings. The relations between the Doppler parameters and heart rate, age, and body surface area were analyzed separately for the children below and above 6 months of age. The normal values for the two groups are given as the median and range and as the mean and standard deviations, respectively. For the older age group, strong negative correlations with heart rate were found for stroke distance and ejection time, suggesting that these parameters should be evaluated in relation to heart rate. Intraobserver and interobserver reproducibility were studied in 10 children. Good reproducibility was found for stroke and minute distance, peak velocity, and left ventricular ejection time. For measurements related to acceleration, the reproducibility was less good. PMID- 7997427 TI - Single daily dose of digoxin for maintenance therapy of infants and children with cardiac disease: is it reliable? AB - Between July 1990 and September 1991, 30 infants and children, most of whom had a congenital heart defect and who had been treated at least during the previous 20 days by two daily doses of digoxin and were in a stable clinical condition, were selected at random. A maintenance dose of digoxin was administered at 24-h intervals for 7 days in the study group (n = 15); no change was made in the 12-h dosage interval in the control group (n = 15). When the serum digoxin concentrations were compared, no significant difference was found between pre- and poststudy values in the study group (1.0 +/- 0.6 and 0.8 +/- 0.3 ng/ml, respectively) or between the control and study groups (0.9 +/- 0.6 and 0.8 +/- 0.3 ng/ml, respectively) in terms of trough serum digoxin concentrations. Although the peak serum concentrations in the study group were increased significantly (2.3 +/- 0.8 ng/ml) compared with prestudy peak levels (1.6 +/- 0.7 ng/ml, p < 0.05) and with the level in the control group (1.5 +/- 0.8 ng/ml, p < 0.05), a toxic concentration was not reached, and toxicity symptoms were not observed clinically. Blood pressure, heart rate, and liver size did not change significantly in any patient during the study. PMID- 7997426 TI - Doppler echocardiographic evaluation of left ventricular diastolic function after surgical correction of atrial septal defect during childhood. AB - Transmitral flow was studied using Doppler echocardiography with the A/E ratio as a parameter of left ventricular diastolic function in 21 patients (ages 2.5-30.0 years) who had undergone early surgical correction of an isolated secundum type atrial septal defect (ASD) compared to a healthy cohort of 21 subjects. Pre- and postoperative M-mode recordings were compared in 12 of the 21 patients to evaluate the effect of operation on interventricular septal motion (IVS) and left ventricular (LV) and right ventricular (RV) end-diastolic diameter ratio (LVDD/RVDD) as parameters of right ventricular volume overload. No significant difference in A/E ratio was found between the patient and control groups. IVS was shown to normalize in 11 of 12 patients postoperatively and to improve from paradox to flattened in 1 of 12. LVDD/RVDD increased from 1.26 +/- 0.31 to 2.10 +/- 0.51 (p = 0.0008), with no significant difference remaining between the control and patient groups postoperatively. These findings support the conclusion that an intrinsic abnormality of the left ventricle is not responsible for its diastolic dysfunction in patients with ASD who develop left ventricular failure, thereby implicating an acquired abnormality. Mechanical sequelae of right ventricular volume overload were shown to normalize in all patients subsequent to operation in the present study, and therefore cannot be excluded as a cause of left ventricular failure in ASD. PMID- 7997429 TI - Traumatic ventricular septal defect after a kick by a cow. AB - A case is presented of an unusual rupture of the ventricular septum due to a kick from a cow. The 7-year-old boy developed acute cardiac failure. The electrocardiogram showed anterior and apical myocardial infarction. Two dimensional color and Doppler echocardiography revealed a rupture of the ventricular septum. The traumatic ventricular septal defect was successfully closed using a right atrial approach. PMID- 7997428 TI - Primary intraventricular cardiac tumors in children: contemporary diagnostic and management options. AB - We reviewed the intraventricular cardiac tumors presenting at our institution between 1985-1991, studying the presentation, modes of investigation, and evidence of hemodynamic compromise. Thirteen patients presented with intraventricular tumors during the study period. Two of the tumors were rhabdomyosarcomas, one was a myxoma, and 10 were rhabdomyomas. All patients were evaluated with two-dimensional and pulsed Doppler echocardiography and B-color imaging was undertaken in three patients. Four patients presented for elective scans to complement investigations for tuberous sclerosis, seven patients had cardiac symptoms, and two patients presented prenatally. Obstruction to intracardiac flow was present in five patients. Two patients had the tumor excised and one had an open biopsy of the tumor. One patient had an transvascular biopsy at cardiac catheter. Early detection of cardiac tumors is increasing, particularly rhabdomyomas. With fetal echocardiography, more patients should come to attention prenatally. B-color may be useful addition in assessing cardiac tumors, aiding detection and definition of intramural lesions. PMID- 7997430 TI - Intra-utero diagnosis of anomalous right ventricular muscle bundles in association with a ventricular septal defect: a case report. AB - The morphology and natural history of anomalous right ventricular muscle bundles (ARVMB) have been described in a number of postnatal studies. Whether this is a congenital or acquired cardiac lesion remains obscure. A fetal echocardiogram performed in a 32-week gestation mother showed a large ventricular septal defect and anomalous right ventricular muscle bundles, which were easily appreciated at the ostium-infundibular level. The diagnosis was confirmed postnatally and at 6 months of age the child underwent surgical repair. This report documents the presence of ARVMB in a fetus, at a time when hemodynamics cannot explain the development of right ventricular muscle bundles. It suggests that at least, the morphologic substrate for this disease is congenital. PMID- 7997432 TI - Total anomalous pulmonary venous drainage and mitral atresia. PMID- 7997431 TI - Hyperuricemia in an infant with Taussig-Bing anomaly and interruption of the aortic arch. AB - Hyperuricemia is commonly recognized in adolescents and adults with cyanotic congenital heart disease. We report a case of a male infant with hyperuricemia, Taussig-Bing anomaly, and interruption of the aortic arch. The patient underwent correction of interrupted aortic arch and pulmonary arterial banding at the age of 7 days. Hyperuricemia appeared when he was 2 months old (max 17.7 mg/dl) and persisted until he underwent a Jatene operation at the age of 10 months. The hyperuricemia improved gradually after the disappearance of hypoxia and polycythemia. The laboratory findings suggest that hyperuricemia can result from uric acid overproduction due to secondary polycythemia, impairment of uric acid excretion by the kidney, or the acceleration of anaerobic metabolism. Allopurinol and benzbromarone together were partially effective treatments for hyperuricemia in this patient with cyanotic congenital heart disease. PMID- 7997433 TI - Immunohistochemical localization of estrogen-specific 17 beta-hydroxysteroid oxidoreductase in the human and mouse prostate. AB - The estrogen-specific 17 beta-hydroxysteroid oxidoreductase (17 beta-HSOR) enzyme protein was stained immunohistochemically in the newborn and adult human prostate as well as in the mouse prostate. In the newborn human prostate, ductal and urethral epithelia were faintly stained, whereas in the adult human prostate, intense staining for 17 beta-HSOR enzyme antigen could be detected in the epithelium of the collecting ducts and urethral epithelium as well as in the epithelium of the intraprostatic vas deferens and seminal vesicle epithelium. Immunostaining was weak in the prostatic tissues of both newborn and adult prostate. No positive cells were found in stroma. The activity of NADPH-dependent 3H-estrone reductase was detectable in cell-free homogenates prepared from human prostatic tissues. The activities showed a good correlation with immunocytochemical findings. In the mouse, neonatal estrogenization resulted in intensively stained epithelium of the collecting ducts at the age of 14 days. Moreover, when adult control and neonatally estrogenized mice were implanted with 17 beta-estradiol, the metaplastic epithelium of the periurethral collecting ducts of neonatally estrogenized mice was intensively stained with 17 beta-HSOR. These findings suggest that metaplastic epithelium rises from 17 beta-HSOR positive cells. The similar distributions of 17 beta-HSOR-positive cells confirm the concept of homology in the posterior estrogen-responsive periurethral region (containing the periurethral ducts and periurethral glands) of the mouse and humans. Our findings further suggest that the 17 beta-HSOR-positive cells may have the same origin and hormonal control in both species. PMID- 7997434 TI - Proliferation-dependent vs. independent programmed cell death of prostatic cancer cells involves distinct gene regulation. AB - Androgen-independent Dunning R-3327 AT-3 rat prostatic cancer cells can be induced to undergo programmed cell death in either a proliferation-dependent or independent manner depending upon the therapeutic agent used. In the present study, 5-fluorodeoxyuridine (5-FrdU) was used to induce proliferation-dependent death of the AT-3 cells via its ability to inhibit thymidylate synthetase. Ionomycin and thapsigargin were used to induce proliferation-independent death of these cells via their ability to sustain an elevation in intracellular free Ca2+. Based upon the temporal sequence of DNA fragmentation, morphologic changes, and loss of cell viability, each of the three test agents, at the doses used, induces the programmed death of AT-3 cells with essentially identical kinetics. Based upon these similarities, comparisons of the pattern of gene expression during the proliferation-dependent (i.e., 5-FrdU-induced) vs. proliferation-independent (i.e., ionomycin and thapsigargin-induced) programmed death of AT-3 cells allow identification of genes whose enhanced expression is involved in the initiation vs. completion of programmed cell death. Based upon this approach, enhanced H-ras and TRPM-2 expression is associated with initiation of proliferation-dependent programmed death of AT-3 cells while enhanced c-myc, calmodulin, and alpha prothymosin expression is associated with initiation of proliferation-independent programmed death of these cells. In contrast, enhanced expression of glucose regulated 78 kilodalton and tissue transglutaminase genes are associated with the completion of programmed cell death, since their expression is enhanced in both proliferation-dependent and independent programmed cell death of AT-3 cells. PMID- 7997435 TI - Inhibition of growth and increase of acid phosphatase by testosterone on androgen independent murine prostatic cancer cells transfected with androgen receptor cDNA. AB - Most androgen-unresponsive prostatic cancer cells are found to lack androgen receptor (AR). To clarify the role of AR in the process of the progression from androgen-dependent to androgen-unresponsive tumor, the AR gene was transfected into an AR-negative rat prostatic cancer cell line CUB-II. AR-transfectant cells expressed AR mRNA and showed binding to R1881. AR was found in nuclei of AR transfectant cells by histochemical examination. Therefore, AR-transfectant cells were considered to contain functional AR. The growth of AR-transfectant cells was markedly inhibited in culture in the presence of testosterone, and the effect of testosterone was reduced by simultaneous addition of flutamide. Moreover, tumors inoculated with AR-transfectant cells in male mice showed much slower growth than those in females. The tumors of AR-transfectant cells in mice consisted of slightly larger spindle-shaped cells when compared to those of CUB-II cells. Moreover, AR-transfectant cells contained a few polynuclear giant cells. Since CUB-II cells contained acid phosphatase (AcP) activity, the addition of testosterone in culture increased AcP activity of AR-transfectant cells. It is concluded that resumption of androgen-dependent processes reduces the growth rate accompanying changes of phenotype. PMID- 7997436 TI - Glycosaminoglycans of guinea pig prostate fibromuscular stroma: influence of estrogen and androgen on levels and location of chondroitin sulfate. AB - The effects of aging and hormone manipulation on the glycosaminoglycan (GAG) content of prostatic stroma in guinea pigs were investigated. Total GAG and individual GAG classes (chondroitin, dermatan, and heparan sulfates, and hyaluronic acid) were measured biochemically in stromal extracts. Chondroitin sulfate was also measured and localized by video image analysis of immunocytochemically-stained tissue sections. The weight and total GAG (uronic acid) content of prostatic stroma increased between the ages of 2 weeks and 2 years by 7-8-fold and 4-5-fold respectively. GAG concentration per unit weight of stroma declined 4-fold during puberty and remained essentially unchanged thereafter. Similar results were obtained for each of the GAG classes. The decreases in GAG concentration were associated with a 3-fold increase in the size of the smooth muscle cells of the prostatic stroma during puberty. Hormonal control of GAG deposition in the prostatic stroma was investigated by steroid replacement in prepubertally-castrated animals. Administration of dihydrotestosterone (DHT) to castrate animals for 6 weeks resulted in significantly reduced concentrations of stromal uronic acid, compared with untreated castrate animals (P < 0.05). The GAG levels post-DHT treatment were similar to those observed after pubertal development in sham-operated control animals. Estradiol treatment had the opposite effect to that of DHT, resulting in a significantly increased concentration of uronic acid compared with castrate animals (P < 0.05). These steroid-induced changes in stromal GAG deposition were mostly contributed to by chondroitin and dermatan sulfates. Combined treatment with DHT and estradiol resulted in stromal uronic acid concentrations similar to those of animals receiving DHT alone, indicating that the effect of DHT on stromal GAG deposition is dominant over the effects of estradiol. Morphometric measurement, using computer-assisted video image analysis of a chondroitin sulfate epitope in prostatic sections stained with a monoclonal antibody (6C3), supported the biochemical data. Stereometric profiles across several sectioned glands demonstrated that chondroitin sulfate was confined to the periacinar basement membranes of the prostatic stroma in all groups except the estradiol treated castrate animals, where the immunostaining extended from the periacinar basement membrane throughout the fibromuscular stroma. Treatment of castrate animals with estradiol alone also induced a physicochemical change in the chondroitin sulfate molecule, resulting in reduced electrophoretic mobility. In summary, this study identifies changes in the quantity, structure, and localization of chondroitin sulfate in the prostatic stroma of estradiol-treated guinea pigs. Furthermore, estradiol and DHT have opposing effects on the level of chondroitin and dermatan sulfate expression in the prostatic stroma. PMID- 7997437 TI - Antimicrobial prophylaxis. PMID- 7997438 TI - Fears and phobias. PMID- 7997439 TI - Consultation with the specialist. Anticholinergic medications in pediatric gastrointestinal disease. PMID- 7997440 TI - Index of suspicion. Case 1. Opsomyoclonus due to neuroblastoma. PMID- 7997441 TI - Index of suspicion. Case 2. Splenic injury. PMID- 7997442 TI - Index of suspicion. Case 3. Drug-induced movement disorder. PMID- 7997443 TI - Physical abuse of children: an update. AB - Now, more than ever, physicians must be willing to suspect child abuse and report their concerns. New information from the past decade warns us that reports of violence against children continue to increase. We are learning that MRI imaging of the head may, in some cases, help date subdural hematomas, but long-term developmental follow-up studies of "shaken" infants are lacking. Intentional thoracic and abdominal injuries carry a high mortality. Finally, new information in the field of child abuse--in particular, physical abuse--is slow to come. Lack of funding for basic medical child abuse research and lack of trained researchers in the field are the two most important barriers. Preventive intervention at the community and family level needs to be supported by both the pediatrician and the local and national government leaders. As the U.S. Advisory Board on Child Abuse and Neglect says, "We need to make it as easy for parents to pick up the telephone and get help before they abuse their child as it is now for their neighbor or physician to pick up the telephone and report them after it has happened." Child health practitioners may be in the best position to implement such a policy. PMID- 7997444 TI - Quality improvement: an ACQIP exercise on vaccine administration--Part 1. PMID- 7997445 TI - Pulmonary function testing in pediatric practice. PMID- 7997446 TI - Current topic: human placental Fc receptors. AB - Human immunoglobulin G (IgG) Fc receptors are important in the materno-fetal relationship. Three classes of IgG Fc receptors are recognized which generate multiple isoforms, most of which are expressed in different cellular components of human placenta at different times during pregnancy. Although the distinct biological functions of Fc gamma R phenotypes expressed in human placenta are still unknown, recent data provide evidence for an important association between the Fc gamma R phenotype and transcytosis of IgG in the placenta. Selective transfer of maternal IgG across the placenta provides passive immunity to the fetus during the period when its own immune system is gaining protective potential. Furthermore, placenta-specific macrophages may contribute through Fc gamma R-mediated phagocytosis to the protection of the fetus from either infection or maternal immune attack against paternally inherited fetal antigens. Ontogeny and expression of various isoforms of Fc gamma R subtypes may be the key to the elucidation of the transport mechanism of maternal IgG to the fetus, in addition to the determination of the mechanisms of placental protection of the fetus against the maternal immune system. PMID- 7997447 TI - Placenta-specific growth factor production by splenic cells during pregnancy. AB - Within the last 5 years strong evidence has correlated the successful outcome of pregnancy with various cytokines, which interfere with sperm mobility, fertilization, implantation, trophoblast outgrowth, as well as maternal immunoregulation. The newly arising antigens on the extra-embryonic membranes initiate many mechanisms protective to the fetus and not harmful to the mother, one of which is novel protein synthesis. These events are apparent in many different sites of the maternal organism including the decidual cap, uterine walls, draining lymph nodes, spleen etc. Working on a murine model, in the present study we concentrated on the growth factor production by spleen cells isolated from syngeneically pregnant mice on the 11th day of gestation. Focusing our interest on the proteins that have a stimulatory effect on placental cells, we fractionated 24 h spleen cell supernatants through a G-25 Sephadex followed by a Heparin-Sepharose affinity column and isolated pregnancy specific growth factors capable of inducing placental cell proliferation. In this study we focused on three growth factors, interleukin-3 (IL-3), granulocyte-macrophage colony stimulating factor (GM-CSF) and colony stimulating factor-1 (CSF-1), which have been previously shown to play an important role in placental growth. CSF-1 and IL-3 were detected in single Heparin-Sepharose fractions, whereas GM-CSF was found dispersed in essentially three fractions. Although we were able to detect these three growth factors in specific affinity column fractions, other proteins, which we have not yet characterized, showed significant biologic activity. Such biologic activity could not be detected from non-pregnant spleen cell supernatants similarly fractionated.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7997448 TI - The release of human chorionic gonadotrophin and placental lactogen by placental explants can be stimulated by Ca2+ entry through a Na(+)-Ca2+ exchange process. AB - Isosmotical replacement of extracellular Na+ ([Na+]o) by K+, choline and to a lesser extent by saccharose stimulated the release of chorionic gonadotrophin and placental lactogen from human term placental explants. The effect of [Na+]o removal on the release of both hormones was concentration-dependent and was inhibited in the absence of extracellular Ca2+ or in the presence of 0.5 mM Co2+, a Ca2+ entry blocker. Blockers of the voltage-sensitive Ca2+ channels (20 microM nifedipine and 50 microM methoxyverapamil) or Na+ channels (5 microM tetrodotoxin) did not affect the stimulatory effects of [Na+]o omission. By contrast, Mg2+ and Sr2+ (10 mM) as well as amiloride (2 mM) and its analogue 2',4'-dimethylbenzamil (50 microns), all known to affect the Na(+)-Ca2+ exchange, markedly reduced the increase in hormone release elicited by [Na+]o removal. Lastly, the secretory responses to [Na+]o deprivation were increased in the presence of 2 mM ouabain, an inhibitor of the Na(+)-K+ ATPase. These results indicate for the first time that [Na+]o omission provokes a Ca(2+)-dependent stimulation of human chorionic gonadotrophin and placental lactogen releases. The pharmacological dissection of the secretory effects of [Na+]o removal supports the existence of a process of Na(+)-Ca2+ exchange in placental cells. PMID- 7997450 TI - Placental cell release of transferrin: analysis by reverse haemolytic plaque assay. AB - Recent demonstrations of transferrin (TF) mRNA in placental tissue raised the possibility that the placenta may serve as an extra-hepatic source of this iron binding protein during development. In this study, we first confirmed these findings using cRNA probes for TF, and then adapted the TF reverse haemolytic plaque assay for use with rat placental cells to identify the location and functional characteristics of cells secreting this product. We found TF releasing cells in placentae (day 19-21) with greater proportions present in cultures from basal than labyrinth zone regions. These cells appeared quite stable as evidenced by observations that fresh populations and 24, 48 and 72 h cultures from the same placental regions all contained similar percentages of secretors. The rate of TF plaque formation was greatly enhanced in the presence of tumour necrosis factor (0.1 ng/ml) for basal zone and yolk sac cells, but not for labyrinth zone cells, suggesting a potent but regionally specific modulation of TF release. When taken together, these findings demonstrate clearly that TF is released from cells of the placenta. Moreover, the regional differences in frequency and modulation of these cells suggests that the release of placental TF is a dynamic and carefully controlled process. PMID- 7997449 TI - Prorenin secretion from villous placenta: regulation by cyclic AMP and angiotensin. AB - Renin synthesis and secretion from human chorion and decidua have previously been shown to be stimulated by agents which increase cellular cyclic adenosine monophosphate (cAMP). We have now used organ culture of villous placenta, incubated for periods up to 72 h, to investigate the cellular regulation of renin in this tissue. The placental tissues release renin (92-96% in the form of prorenin) and human chorionic gonadotrophin (hCG), but not prolactin. We found that cholera toxin and forskolin markedly stimulate the synthesis and release of renin in a time-dependent manner. This stimulation was potentiated by phosphodiesterase inhibitors and inhibited by an angiotensin II agonist, sar-1 angiotensin II. The inhibitory action of the angiotensin agonist on renin release was blocked by sar-1-leu-8-angiotensin II, a selective angiotensin receptor antagonist. The potential for stimulation of renin expression by cyclic AMP regulated elements is supported by the dramatic (two-orders of magnitude) increase in renin release observed with cholera and forskolin at 72 h. There are several possible candidates for primary signals for adenylyl cyclase-coupled renin secretion from the placenta, including relaxin and epinephrine. The extremely low concentration of renin in term villous placenta may be related to activation of negative regulatory elements on the renin gene. We propose that angiotensin II is one negative regulator of this system. PMID- 7997451 TI - Immunohistochemical detection of lipoprotein(a) in the wall of placental bed spiral arteries in normal and severe preeclamptic pregnancies. AB - In normal pregnancy trophoblast invades the spiral arteries and produces the physiological fibrinoid degeneration of the vessel wall. In pre-eclampsia, physiological change is restricted and pathological change develops in the non invaded arteries, including acute atherosis. This study was undertaken to determine if lipoprotein(a) [Lp(a)], which is associated with atherogenesis is present in the wall of spiral arteries that have undergone physiological and pathological change. One hundred and sixteen spiral arteries were examined from 18 normal and 24 severe pre-eclamptic pregnancies. Lp(a) was detected in all atherotic and necrotic lesions, in 57% of spiral arteries with medical disorganization or hyperplasia, and in 45% of those with physiological change. When Lp(a) was detected differences were found in the amount seen: it was most in atherosis, less in necrosis, less still in medical change, and least in physiological change. For the same vascular change generally more Lp(a) was detected in the pre-eclamptic group than in the normal group. The detection of Lp(a) helps to distinguish physiological fibrinoid from atherotic and necrotic fibrinoid. Many atherotic and necrotic areas initially overlooked using standard histology were highlighted using immunohistochemistry. Atherosis can develop in spiral arteries that have been invaded by trophoblast. In those with pre eclampsia, atherosis was found in 56% of decidual but only in 8% of myometrial spiral arteries. Small areas of necrosis were common in physiologically changed arteries from normal pregnancies. PMID- 7997452 TI - Evidence that Fc gamma receptors in rabbit yolk sac endoderm do not depend upon an acid pH to effect IgG binding and transcytosis in vitro. AB - An in vitro culture system has been devised creating apical and basal compartments separated by rabbit visceral yolk sac (VYS) with an intact epithelium. Selective transcytosis and binding of heterologous IgG applied to the apical yolk sac endoderm (YSE) was demonstrated in vitro using double label immunofluorescence. Thus, whilst both human and bovine IgG could be detected in endosomes in YSE, only human IgG could be detected in the basement membrane and vascular mesenchyme. This mirrors what is found in vivo. The Fc fragment of human Ig was transcytosed but not the Fab fragment, indicating that Fc receptors were expressed in the cultured YSE. When VYS was previously chilled to 4 degrees C to prevent endocytosis and treated with rabbit serum albumin to prevent non-specific binding, human IgG, but not bovine IgG, became specifically bound to YSE apical plasma membrane; comparison of binding at pH 6.0, 7.3 (the average pH of rabbit uterine fluid) and 8.0 revealed no obvious difference. Pre-exposure of VYS for up to 5 min in monensin, followed by culture in monensin and immunoglobulin containing medium, did not prevent the selective transcystosis of human IgG, suggesting that an acidic compartment may not be needed for transcytosis. An acid pH dependent Fc gamma receptor equivalent to that on suckling rat gut jejunal enterocyte plasma membranes could not be isolated from rabbit YSE following exposure of solubilized membrane to affinity matrix bound IgG at pH 6.0 and elution at pH 8.0. These results contradict a recent suggestion that Fc receptors on all IgG transcytosing epithelia require an acid pH to effect IgG binding and selective transcytosis. PMID- 7997453 TI - Genetic analysis of hydatidiform moles utilizing the oligonucleotide-DNA typing of the HLA-DRB gene. AB - The genetic origin of hydatidiform moles was analysed utilizing HLA-DNA typing. Using HLA-DR type-specific oligonucleotide probes, the DRB types of seven moles were determined and compared with the parental DRB types to determine the paternal and/or maternal origin of the moles. In four cases, the molar tissues showed single DRB types of paternal origin, although in one, the molar DRB type was also possessed by the mother. These four moles were, therefore, considered to be androgenetic in origin. Chromosomal karyotyping was carried out for three of these cases and confirmed the DR-DNA typing results. Two moles demonstrated a DRB type triplet, which strongly suggested triploidy. Although one mole showed a heterozygous DRB type, karyotyping indicated triploidy (69, XXX) and suggested that this mole was caused by dispermy-fertilization, in which both of the sperms had the same DRB type. Although the majority (about 80%) of partial hydatidiform moles have been reported to be triploid as a result of dispermy, four of the moles analysed in this study (cases 1, 2, 3 and 4), diagnosed as partial macroscopically and/or histopathologically, were found to be androgenetic in origin using karyotyping and DR-DNA typing. Therefore, HLA-DR DNA typing, combined in some cases with karyotyping, provides an accurate method for diagnosing androgenesis and triploidy in complete and partial hydatidiform moles. PMID- 7997454 TI - Comparison of villous trophoblast proliferation rate in hydatidiform mole and non molar abortion by assessment of proliferating cell nuclear antigen expression. AB - This study examines the proliferative activity of trophoblast in hydatidiform mole, non-molar hydropic abortion and non-molar spontaneous abortion. Nine cases of complete mole, 10 cases of partial mole, eight cases of non-molar hydropic abortion and six cases of non-hydropic second trimester abortion were examined by routine histopathology and the rate of cell proliferation was assessed by immunoreactivity for proliferating cell nuclear antigen (PCNA). Hydropic abortion showed a significantly lower PCNA index than complete mole and partial mole. There was no significant difference in PCNA index between partial mole and non hydropic abortion. The trophoblast of partial hydatidiform mole demonstrates significant cell proliferation but this, although higher than that of hydropic abortion, is no higher than that of non-hydropic abortion of a similar gestational age. The role of partial mole as a precursor of persistent gestational trophoblastis disease remains unclear. PMID- 7997455 TI - Short report: identification of a specific pattern of vascular endothelial growth factor mRNA expression in human placenta and cultured placental fibroblasts. AB - Reverse transcription and the polymerase chain reaction (PCR) were used to detect vascular endothelial growth factor (VEGF) mRNA in human placental tissue and cultured placental fibroblasts obtained during the first trimester of pregnancy. The primers for VEGF corresponded to areas in exon 4 and exon 8 of the VEGF gene. After one round of PCR three products, equivalent to VEGF121, VEGF165 and VEGF189, were detected within placental tissue and cultured placental fibroblasts. A further round of PCR revealed the presence of two more products equivalent to VEGF206 and VEGF145. Thus, in addition to the production of readily secreted forms of VEGF (VEGF121 and VEGF165), the placenta produces several transcripts expected to increase the growth factor pool of the extracellular matrix. PMID- 7997456 TI - [The modern problems of space cell phytobiology]. AB - This monograph has summarized the results of space experiments fulfilled over the last 25 years on lower and higher plants cell and tissue cultures in vitro being physiologically active during the space mission. A considerable attention has been paid to the calcium ions role in biological effects at the cellular and subcellular levels of microgravity and clinostating, physical-chemical features of cytoplasmic membrane and lipid peroxidation of plant cells under conditions of gravity variations. The rearrangement patterns of the plant cell structural functional organization affected by microgravity and clinostating and probable mechanisms of cell adaptation to these factors are discussed. PMID- 7997457 TI - Annual subject and author indexes. PMID- 7997458 TI - Fluctuating asymmetry in the Mus musculus hybrid zone: a heterotic effect in disrupted co-adapted genomes. AB - Developmental stability reflects the organism's ability to buffer minor developmental accidents and is often estimated by measuring the fluctuating asymmetry. Either implicitly or explicitly, numerous authors have assumed that developmental stability is correlated with overall fitness. If this is the case, changes in morphological asymmetry across a hybrid zone could be used as a measure of the selection on hybrid genomes. Developmental stability in hybrid populations is theoretically related to the genetic distance between hybridizing taxa, and results from a balance between the stabilizing effect due to increased heterozygosity and the disruptive effect caused by breakdown of genomic co adaptation. Here we have compared the amount of fluctuating asymmetry across a transect of the hybrid zone between the two European subspecies of the house mouse (Mus musculus domesticus and M. m. musculus) in Denmark. For the first time in any natural hybrid zone we found an increased developmental stability in the populations with mixed genomes. Moreover, the apparently beneficial effect of hybridization on the developmental stability of the hybrid mice contrasts with the results of both genetic and parasitological studies which show that hybrid dysgenesis occurs in this zone. Our results suggest that the barrier to gene flow in the Mus musculus hybrid zone may result from the disruption of relatively few gene systems. They also lead us to reassess the relation between developmental stability expressed as fluctuating asymmetry, co-adaptation and overall fitness. PMID- 7997459 TI - Cytochalasin D blocks touch learning in Octopus vulgaris. AB - Supraoesophageal lobes in 11 specimens of Octopus vulgaris were split sagitally into two symmetrical halves and isolated by a thin inert mica barrier. Each half brain is known to control the four arms on its side of the animal and to be able to learn opposite touch paradigms mediated by its four arms. Powdered cytochalasin D was applied directly in each animal to the subfrontal lobe of one half-brain, and both half-brains were then trained to opposite touch paradigms. The cytochalasin treated half-brains could not learn either touch paradigm whereas the control half-brains learned readily. In another set of four animals, cytochalasin D was similarly applied but to the vertical lobe of one half-brain. In this case all the half-brains learned the touch paradigm. PMID- 7997460 TI - Manifestations of sexual selection may depend on the genetic bases of sex determination. AB - A variant of the 'handicap' model of sexual selection is described which predicts that the evolution of ornate male traits occurs more easily in species where females are the heterogametic sex. The process occurs even when the alleles conferring high paternal 'fitness' remain advantageous for only a short time due to a rapidly changing physical or biotic environment: the timescale of this advantage may approach the gestation time of the organism. This provides an explanation as to why sexual selection in species where females are heterogametic (such as birds) occurs mainly by the elaboration of ornate male secondary sexual characteristics, whereas in species where females are homogametic (such as mammals) sexual selection results predominantly in inter-male rivalry and the evolution of traits such as horns, antlers and large body size. An analogy between the evolution of elaborate male traits and the evolution of warning coloration is noted. PMID- 7997462 TI - Antinociceptive mechanism of the aconitine alkaloids mesaconitine and benzoylmesaconine. AB - We explored the possible role of the specific regions in the brain stem on the antinociceptive actions of mesaconitine (MA) and benzoylmesaconine (BM) by the microinjection of MA and BM into nucleus reticularis paragigantocellularis (NRPG), nucleus raphe magnus (NRM), and periaqueductal gray (PAG). MA microinjected into NRPG, NRM, or PAG elicited a dose-dependent antinociceptive action, whereas BM injected into NRM or PAG elicited a dose-dependent antinociceptive action but not in NRPG. The NRM appeared to be the most sensitive region among the three tested locations. PMID- 7997461 TI - The astrocyte response to gamma-aminobutyric acid attenuates with age in the rat optic nerve. AB - There is increasing evidence that glial cells respond to the inhibitory neurotransmitter gamma-aminobutyric acid (GABA), and astrocytes have been shown to possess GABAA receptors both in vivo and in vitro. A recent study by Sakatani et al. (Proc. R. Soc. Lond. B247, 155 (1992)) demonstrated the transient expression of functional GABAA receptors in the developing rat optic nerve, but axonal and glial components of the response were not distinguished. To help address this problem, we have determined the electrophysiological response to GABA in astrocytes of the isolated intact optic nerves from neonatal rats, identified morphologically following intracellular injection of horseradish peroxidase. Astrocytes responded to GABA by a GABAA receptor-mediated depolarization which attenuated gradually during post-natal development; astrocytes in 21-day-old nerves were not observed to respond to GABA. The results indicate the transient presence of functional GABAA receptors in developing rat optic nerve astrocytes in situ, and we speculate upon a role for GABA in glial signalling and the organization of axonglial interrelations during development. PMID- 7997463 TI - Antinociceptive, anti-inflammatory and antipyretic effects of lapidin, a bicyclic sesquiterpene. AB - Lapidin, a bicyclic sesquiterpene from Ferula linkii Webb, has been evaluated for antinociceptive, anti-inflammatory, and antipyretic activities in mice and rats. Lapidin, vehicle, or the appropriate reference analgesic and anti-inflammatory compounds (acetylsalicylic acid [ASA] and indomethacin) were injected i.p. The more conspicuous effects of lapidin were: 1) a significant protective effect (17 62%; 2.5-20 mg/kg) towards writhings and stretchings induced by acetic acid in mice; 2) a significant antinociceptive effect on jumping responses in the hot plate test (120 seconds at 15 mg/kg vs. 40 and 85 seconds in vehicle and ASA treated mice, respectively); 3) a significant dose-dependent (5-15 mg/kg) antinociceptive effect against mechanical noxious stimuli; 4) a dose-dependent anti-inflammatory effect in the carrageenan-induced edema which, at the higher dose (20 mg/kg), was comparable (65% inhibition of paw swelling at 3 hours) to that obtained after indomethacin (10 mg/kg); and 5) a moderate antipyretic effect against yeast-induced hyperthermia. Present results demonstrate that lapidin possesses antinociceptive, anti-inflammatory, and less pronounced antipyretic effects comparable to those of classical non-steroid anti-inflammatory drugs, which make it worthy of further investigations as an antinociceptive and anti inflammatory drug. PMID- 7997464 TI - Antifertility effects of aqueous extract of Carica papaya seeds in male rats. AB - The influence of the crude aqueous extract of Carica papaya L. (Caricaceae) seeds has been studied on semen profile, fertility, body and organ weight response, and toxicology in male albino rats. The extract was administered at the dose regimens of 10 and 50 mg/animal/day orally for 30, 60, and 90 days and 0.1 and 1.0 mg/animal/day intramuscularly for 15 and 30 days. Cauda epididymal sperm motility and count was reduced significantly at low and high dose regimens both in the oral as well as the intramuscular groups. The reduced sperm motility was associated with morphological defects. Testicular sperm counts were also reduced in all the treatment groups except the low dose intramuscular group. Fertility tests showed dose- and duration-dependent reduction and zero fertility was observed at high dose regimens of the oral and intramuscular groups following 60 and 30 days of treatment, respectively. Testicular weight was reduced in all the treatment groups, whereas accessory sex organs showed a variable response. Body weight and toxicological observations did not show any untoward response. Fertility and all other associated changes returned to normal within 45 and 30 days of treatment cessation in the oral and intramuscular groups, respectively. The data revealed that reversible sterility could be induced in male rats by papaya seeds aqueous extract treatment without adverse effects on libido and toxicological profile. PMID- 7997465 TI - Effects of tanshinone VI derivatives on post-hypoxic contractile dysfunction of perfused rat hearts. AB - The present study was undertaken to elucidate the effects of sodium tanshinone VI 1-phenolate (1), 1'-O-hydrogen succinyltanshinone VI 1-O-hydrogen succinate (2), and disodium 1'-O-succinyltanshinone VI 1-O-succinate (3), water-soluble derivatives of tanshinone VI, on post-hypoxic contractile recovery of isolated perfused rat hearts. The effects were compared with those of tanshinone VI as tested previously. The hearts were perfused for 20 min under hypoxic conditions, followed by 45 min reoxygenation, and their cardiac performance was determined. Changes in tissue sodium, potassium, calcium, and magnesium contents after reoxygenation, and release of creatine kinase and purines and bases (ATP metabolites) during hypoxia/reoxygenation were also examined. The derivatives were dissolved in a Krebs-Henseleit buffer and administered at concentrations of 42 nM into the buffer. Hypoxia/reoxygenation resulted in slight recovery of cardiac contractile force, significant alterations in tissue ion concentrations, and pronounced release of creatine kinase and ATP metabolites, suggesting hypoxia/reoxygenation-induced functional and morphological damage. The tanshinone VI derivatives improved post-hypoxic contractile recovery, which was associated with restoration of tissue ionic concentrations, and diminishment of the release of creatine kinase and ATP metabolites from the hypoxic/reoxygenated hearts. The efficacy of these compounds was similar to that of tanshinone VI. The results suggest that water-soluble tanshinone VI derivatives, like tanshinone VI itself, are beneficial for hypoxia/reoxygenation injury. PMID- 7997466 TI - Chamazulene: an antioxidant-type inhibitor of leukotriene B4 formation. AB - Matricine and its transformation product chamazulene are constituents of chamomile extracts. Both have been demonstrated to exert anti-inflammatory activity in vivo. Since preparations from chamomile are used for the treatment of inflammatory skin and bowel diseases, we studied the effects of these compounds on the leukotriene production in neutrophilic granulocytes. Chamazulene inhibited the formation of leukotriene B4 in intact cells and in the 105,000 x g supernatant fraction in a concentration-dependent manner. The IC50 values were 15 and 10 microM, respectively. Matricine showed no effect up to 200 microM. Chamazulene (IC50: 2 microM), but not matricine, blocked the chemical peroxidation of arachidonic acid. Additionally, matricine (up to 200 microM) had no effects on the cyclooxygenase and 12-lipoxygenase activities in human platelets. Therefore, it is concluded that chamazulene, but not matricine, may contribute to the anti-inflammatory activity of chamomile extracts by inhibiting the leukotriene synthesis and additional antioxidative effects. PMID- 7997467 TI - Suppression of chemically and immunologically induced hepatic injuries by gentiopicroside in mice. AB - Gentiopicroside (GPS), a main bitter secoiridoid constituent of roots of Gentiana macrophylla Pall., was tested for therapeutic effects on the two hepatic injury models, the CCl4-induced and lipopolysaccharide (LPS)/bacillus Calmette-Guerin (BCG)-induced hepatitides. An increase in serum level of hepatic aminotransferases (GOT: EC 2.6.1.1. and GPT: EC 2.6.1.2.) induced by a p.o. treatment of CCl4 was suppressed by pretreatment with GPS at 30-60 mg/kg/day for 5 consecutive days. An increase of these enzymes triggered by an i.v. treatment with LPS in mice primed with bacillus Calmette-Guerin (BCG) was also inhibited by GPS pretreatment at the same dose of GPS. In the BCG/LPS model, tumor necrosis factor (TNF), a major inflammatory mediator, was increased in serum with a peak at 90-120 min, followed by an increase of serum transaminase activities. GPS treatment significantly suppressed the increase of TNF in serum at the therapeutic doses, suggesting that GPS protected against hepatitis by inhibiting the production of TNF. PMID- 7997468 TI - Antioxidant and radical scavenging effects of aged garlic extract and its constituents. AB - The antioxidant properties of three garlic preparations and organosulfur compounds in garlic have been determined. Aged garlic extract inhibited the emission of low level chemiluminescence and the early formation of thiobarbituric acid-reactive substances (TBA-RS) in liver microsomal fraction initiated by t butyl hydroperoxide. However, the water extracts of raw and heat-treated garlic enhanced the emission of low level chemiluminescence. Among the variety of organosulfur compounds, S-allylcysteine (SAC) and S-allylmercaptocysteine (SAMC), the major organosulfur compounds found in aged garlic extract, showed radical scavenging activity in both chemiluminescence and 1,1-diphenyl-2-picrylhydrazyl (DPPH) assays, indicating that these compounds may play an important role in the antioxidative activity of aged garlic extract. PMID- 7997469 TI - The antipsoriatic Mahonia aquifolium and its active constituents; I. Pro- and antioxidant properties and inhibition of 5-lipoxygenase. AB - The effects of the extract of the bark of Mahonia aquifolium and its main constituents (berberine, berbamine, oxyacanthine) on 5-lipoxygenase, lipid peroxidation in phospholipid liposomes induced by 2,2'-azo-(bis-2 amidinopropane), deoxyribose degradation, and their reactivities against the free radical 2,2-diphenyl-1-picrylhydrazyl have been studied. The extract of M. aquifolium inhibits 5-LO with an IC50 value of 50 microM, whereas no appreciable effects were observed by its constituent alkaloids. Reactivity against DPPH increased in the following order: berberine < M. aquifolium < oxyacanthine, berbamine. Pro-oxidant effects by M. aquifolium or its constituents can be excluded, since deoxyribose degradation was not influenced as determined by the release of malondialdehyde. The most prominent feature of M. aquifolium is its efficacy in inhibition of lipid peroxidation (IC50 = 5 microM) which was not mediated by the alkaloids berberine, berbamine, and oxyacanthine. PMID- 7997470 TI - Polyclonal antibody against a complement-activating pectin from the roots of Angelica acutiloba. AB - Anti-sera against a complement-activating pectin (AR-2IIb), which was purified from the roots of Angelica acutiloba Kitagawa, were obtained by immunization of rabbits, and a polyclonal anti-AR-2IIb antibody of the IgG class was purified by affinity chromatography on AR-2IIb-immobilized Sepharose and Protein G-Sepharose. Periodate oxidation of AR-2IIb significantly reduced its inhibitory activity on the reactivity of AR-2IIb to anti-AR-2IIb-IgG, but pronase digestion of AR-2IIb did not affect its inhibitory activity. Other pharmacologically active pectins from A. autiloba, Bupleurum falcatum, and Glycyrrhiza uralensis and the complement-activating pectic arabinogalactan from A. autiloba also showed significant inhibitory activities on the reactivity of AR-2IIb to anti-AR-2IIb IgG, but these inhibitory activities were lower than that of AR-2IIb. Other pectins, polygalacturonic acid, arabinogalactan, galactan, and araban tested had negligible inhibitory activity. Endo-a-(1-->4)-polygalacturonase digestion of AR 2IIb indicated that its "ramified" region (rhamnogalacturonan core possessing neutral oligosaccharide side-chains) contained epitopes for anti-AR-2IIb-IgG, but that 2-keto-3-deoxyoctulosonic acid (KDO)-containing regions and oligogalacturonides obtained from AR-2IIb were not recognized by anti-AR-2IIb IgG. Although carboxyl-reduction of galacturonic acid in the "ramified" region decreased the inhibitory activity of the "ramified" on its reactivity to anti-AR 2IIb, an acidic tetrasaccharide unit in the rhamnogalacturonan core had negligible inhibitory activity. PMID- 7997471 TI - Activity of extracts of Kigelia pinnata against melanoma and renal carcinoma cell lines. AB - Serial dilutions of standardised water, ethanol, and dichloromethane extracts of the stembark and fruits of Kigelia pinnata were tested for their growth inhibitory effects against four melanoma cell lines and a renal cell carcinoma line (Caki-2) using two different (MTT and SRB) assays. Lapachol, a possible constituent of these extracts, together with known therapeutic antineoplastic agents, was also tested in the same way. The IC50 of each extract was measured after extracts were diluted to 100 micrograms/ml in 1% ethanol or water. Significant inhibitory activity was shown by the dichloromethane extract of the stembark and lapachol (continuous exposure). Moreover, activity was dose dependent, the extract being less active after 1 h exposure. Chemosensitivity of the melanoma cell lines to the stembark was greater than that seen for the renal adenocarcinoma line. In marked contrast, sensitivity to lapachol was similar amongst the five cell lines. Lapachol was not detected in the stembark extract. PMID- 7997472 TI - Cytotoxicity of flavonoids and sesquiterpene lactones from Arnica species against the GLC4 and the COLO 320 cell lines. AB - The cytotoxicity of 21 flavonoids and 5 sesquiterpene lactones, as present in Arnica species, was studied in GLC4, a human small cell lung carcinoma cell line, and in COLO 320, a human colorectal cancer cell line, using the microculture tetrazolium (MTT) assay. Following continuous incubation, most flavonoids showed moderate to low cytotoxicity, as compared with the reference compound cisplatin (IC50 = 1.1 microM against GLC4 and 2.9 microM against COLO 320). Their IC50 values varied from 17 to > 200 microM. The most toxic compound was the flavone jaceosidin. Of the sesquiterpene lactones tested, helenalin, possessing both the reactive alpha-methylene-gamma-lactone moiety and a reactive alpha,beta unsubstituted cyclopentenone ring, displayed the strongest cytotoxicity. For 2 h exposure, its IC50 value was 0.44 microM against GLC4 and 1.0 microM against COLO 320. COLO 320 was more sensitive than GLC4 for many flavonoids (especially for flavones), but more resistant to the cytotoxic effect of the sesquiterpene lactones bearing an exocylic methylene group fused to the lactone function. PMID- 7997473 TI - Post-harvest degradation of carotenoid glucose esters in saffron. AB - It has been found that an indoor cultivation system of Crocus sativus L. is more favorable with regard to the quality of saffron, as compared to the usual cultivation in an open field. Carotenoid glucose esters increase from the period before blooming and reach the maximum in the full blooming period, and are sensitive for the presence of oxygen, light irradiation, and beta-glucosidase. Moreover, it is evident that storage of saffron at -20 degrees C promotes the constant supply of saffron with a homogeneous pharmacological activity. PMID- 7997474 TI - Biotransformation of the naturally occurring lignan (-)-arctigenin in mammalian cell lines genetically engineered for expression of single cytochrome P450 isoforms. AB - V79 Chinese hamster cells genetically engineered for stable expression of single forms of rat cytochromes P450 1A1, P450 1A2, and P450 2B1, and human P450 1A2 were used to analyse the metabolism of (-)-arctigenin. Concentrations of metabolites formed in the medium were determined by TLC, HPLC, GC, and GC-MS. Only in the cell line expressing rat P450 2B1 was (-)-arctigenin metabolized to a significant extent. The lignan was converted by O-demethylation to (-)-3'-O demethylarctigenin. PMID- 7997475 TI - Principle of the bark of Phellodendron amurense to suppress the cellular immune response. AB - We previously reported that Wen-Qing-Yin (Unsei-in), a traditional Chinese blended medicine, inhibited the induction phase of various kinds of delayed type hypersensitivity (DTH) and local graft-versus-host (GvH) reactions, but did not affect humoral immune responses or the effector phase of DTH in experimental animals. In another report, we demonstrated that Phellodendri Cortex (bark of Phellodendron amurense Rupr. Rutaceae) was a component having the most potent suppressive effect on the cellular immune response among the 8 medical plants composing Unsei-in. In the present study, we isolated OB-1 and OB-5 from Phellodendri Cortex as the biologically active principles to suppress local GvH reactions in mice. OB-1 and OB-5 are quaternary base alkaloids known as magnoflorine and phellodendrine, respectively. They suppressed the local GvH reaction, when given i.p. to the host mice at 5-20 mg/kg for 8 consecutive days from the day of spleen cell transfer to cause the reaction. Both OB-1 and OB-5 suppressed picryl chloride-induced delayed type hypersensitivity (PC-DTH) when given i.p. to mice at 10 and 20 mg/kg for 5 consecutive days from the day of the sensitization, but did not suppress it when given at the time of the challenge. These results suggest that OB-1 and OB-5 suppress the induction phase but not the effector phase of the cellular immune response. They are expected to have a value as a new type of immunosuppressor. PMID- 7997476 TI - Existence of a rhamnogalacturonan II-like region in bioactive pectins from medicinal herbs. AB - Unusual component sugars such as 2-methylfucose (2-Me-Fuc), 2-methylxylose (2-Me Xyl), apiose (Api), and aceric acid (AceA) are contained in the bioactive pectins from Bupleurum falcatum, Glycyrrhiza uralensis, and Angelica acutiloba, but not in the other bioactive pectic heteroglycans and arabinogalactans from Chinese and Japanese herbs tested. Each pectin was digested with endo-alpha-(1-->4) polygalacturonase, and gave two enzyme-resistant fractions, PG-1 (rhamnogalacturonan core with neutral sugar side-chains) and PG-2, and an oligogalacturonide fraction (PG-3) by gel filtration on Bio-gel P-30. The PG-2 fractions commonly consisted of unusual sugars such as 2-Me-Fuc, 2-Me-Xyl, Api, AceA, 3-deoxy-D-lyxo-heptulosaric acid (Dha), and 3-deoxy-D-manno-2-octulosonic acid (Kdo) in addition to Rha, Fuc, Ara, Xyl, Man, Gal, Glc, GalA, and GlcA. Lithium degradation of each PG-2 gave a pentosyl-->6-deoxyhexosyl-->6 deoxyhexosyl-->pentitol fragment as a major oligosaccharide in addition to some neutral di- to trisaccharide alditols. Methylation analysis of the lithium degradation products from each PG-2 also indicated that these oligosaccharide alditols mainly consisted of terminal Rha, Araf, Fuc, Xyl, and Gal, 4-linked Rha, 3-linked Fuc, and 3'-linked Api. HPLC analysis showed that PG-2 had molecular heterogeneity. These results indicate that the bioactive pectins from medicinal herbs commonly consist of the minor KDO-containing region which resembles the rhamnogalacturonan II in plant cell walls. PMID- 7997477 TI - Isolation of bis-indole alkaloids with antileishmanial and antibacterial activities from Peschiera van heurkii (syn. Tabernaemontana van heurkii). AB - Extracts from leaves and stem bark of Peschiera van heurkii (Muell. Arg.) L. Allorge (syn. Tabernaemontana van heurkii Muell. Arg., Apocynaceae) have been assayed for antileishmanial and antibacterial activities. The activities were concentrated in the alkaloid fractions which yielded 20 indole and bisindole alkaloids. The strongest leishmanicidal and antibacterial activities were observed with the dimeric alkaloids conodurine (1), N-demethylconodurine (= gabunine) (2), and conoduramine (3). Weak toxicity towards macrophage host cells and strong activity against the intracellular amastigote form of Leishmania were observed for compounds 1 and 2. In vivo, 1 was less active than glucantime (= N methylglucamine antimonate), the drug of reference, while 2 was devoid of activity at 100 mg/kg. PMID- 7997478 TI - Antibacterial and molluscicidal phenolic acids from Spondias mombin. AB - Spondias mombin L. (Anacardiaceae), used in traditional medicine because of its antimicrobial properties, was found to contain a series of 6-alkenyl-salicylic acids. They were isolated from the ethanolic extract of leaves and stems of Spondias mombin by a combination of chromatographic methods. Their structure was determined by NMR and MS techniques as (17:3), (17:2) and (17:1) pelandjuaic acid [or 6-(8'Z,11'Z,14'Z-heptadecatrienyl)-salicylic acid, 6-(8'Z,11'Z heptadecadienyl)-salicylic acid, and 6-(10'Z-heptadecenyl)-salicylic acid, respectively], 6-(12'Z-non-adecenyl)-salicylic acid, and 6-(15'Z-heneicosenyl) salicylic acid, the two last compounds being new ones. These phenolic acids were shown to have a pronounced antibacterial effect against Bacillus cereus, Streptococcus pyogenes, and Mycobacterium fortuitum (minimal bactericidal concentration in a concentration range of 3-25 micrograms/ml), and a molluscicidal effect against the snail Biomphalaria glabrata, an intermediate host in the schistosome life cycle. Because of their high molluscicidal activity (LC90 down to 1-3 ppm), these long-chain salicylic acid derivatives may be important tools in the prevention of schistosomiasis. PMID- 7997479 TI - Effect of the hot-water extract of black tea (Camellia sinensis) on the rat diaphragm. PMID- 7997480 TI - Antibacterial activity of compounds from Rubus pinfaensis. PMID- 7997481 TI - Cytotoxic activity of xanthatin and the crude extracts of Xanthium strumarium. PMID- 7997483 TI - Antibacterial activity of diosquinone isolated from Diospyros tricolor. PMID- 7997482 TI - The amount of GABA present in aqueous extracts of valerian is sufficient to account for [3H]GABA release in synaptosomes. PMID- 7997484 TI - A study on choleretic activity of Salvia desoleana essential oil. PMID- 7997485 TI - The essential oil composition of Dictamnus albus from Turkey. PMID- 7997486 TI - Differential diosgenin accumulation in Costus speciosus and its tissue cultures. PMID- 7997487 TI - Antiviral and antifungal flavonoids, plus a triterpene, from Hebe cupressoides. PMID- 7997488 TI - Britain's open border? PMID- 7997489 TI - Health consequences of youth unemployment. AB - BACKGROUND: Youth unemployment is of increasing importance, not only as a social but also as a clinical problem. METHODS: A prospective study was conducted during a five-year period in a municipality in the northern part of Sweden, where the youth unemployment rate was between 6% and 8%. All 1,083 pupils in the last year of compulsory schooling were included in the study and 98% of them were followed up after five years. The methods of investigation consisted of comprehensive self administered questionnaires as well as blood pressure measurements and interviews with those who had been unemployed. RESULTS: The main results of the study are that there is a greater increase in physical and psychological symptoms as well as smoking habits and use of cannabis among long-term unemployed young people than among those not long-term unemployed. In addition systolic blood pressure, alcohol consumption and crime rate increase more among long-term unemployed boys than among others. CONCLUSIONS: Youth unemployment is associated with increased health symptoms, increased systolic blood pressure and a deterioration in health behaviour. PMID- 7997490 TI - Dental needs of pre-retirement and retired people in an inner-city area. AB - Perceived and normative dental needs were assessed for people of pre-retirement (55-64 years) and retirement age (65-74 years) in Camberwell, London, using a postal questionnaire and dental examination. Of the pre-retirement group, 77% were dentate compared with 65% in the older cohort. The younger age-group were more likely to believe teeth were more important and to perceive a need for dental care. People who attended for the examination were more likely to perceive a need for (64% and 15% respectively) and want treatment (39% and 17%) than non examinees. Also, they were more likely to be unhappy with their appearance (43% and 20%) and to be in pain (42% and 21%). Treatment need was similar for both groups with regard to restorative and extraction needs. However, the retirement group were more likely to have deep periodontal pockets (33% and 8%) and a greater normative need for denture care. PMID- 7997491 TI - Regular eye examinations of diabetic patients in the Finnish health care system. AB - A questionnaire about regular eye examinations of diabetic patients was sent to 1,776 physicians in eastern, western and southern provinces of Finland. The study was a part of a larger questionnaire about the medical care of high blood pressure and diabetes. Of the 1,706 doctors working actively, 950 (56%) completed the questionnaire, and 398 (42%) of them treated diabetic patients and gave their opinions of the ophthalmological care in diabetic patients. Regular eye examinations in type I diabetes were carried out annually by 79% of the physicians. In type II diabetic patients, the figure was 55%. In different provinces, these percentages varied from 61% to 81% in type I and from 38% to 74% in type II diabetes. The eye examination was performed in 54% by the physician who also treated diabetes, otherwise the examinations were performed by an ophthalmologist in a hospital, health centre or in private practice. In southern provinces of Finland, regular eye examinations were performed primarily by ophthalmologists in private practice, in western and eastern provinces they were performed by the doctors who also treated diabetes. Most of the regular annual eye examinations were reported by specialists in general practice and physicians working in health centres. The reported current practice in the regular eye examinations of type I diabetic patients is near the current European and American recommendations, but in type II diabetic patients these recommendations are not met adequately. PMID- 7997492 TI - Serological survey of hepatitis B infection in Tanzania. AB - In 1992, the prevalence of hepatitis B virus (HBV) markers was evaluated in 1004 subjects aged one to 76 years living in urban and rural areas in Tanzania. The overall prevalence rates of hepatitis B surface antigen (HBsAg) and of any HBV marker were 4.4% and 37.0%, respectively. No statistically significant difference by sex was found. The HBsAg prevalence among pregnant women was 4.3% (20/463). The proportion of HBeAg positive among HBsAg positive pregnant women was 10% (2/20). The HBsAg age-specific prevalence was 2.1% in the 1-5 year age-group; peak prevalence (12.1%) occurred in the 6-15 year age-group. Markers of HBV infection were 4.1% by age five years; they increased with advancing age (P < 0.01). Subjects residing in urban areas had statistically significant higher HBV exposure than those residing in rural areas (43.9% vs 27.4%, P < 0.01). Subjects belonging to the largest family size (seven or more members) showed increasing risk (OR 2.9; 95% CI = 1.96-4.28) of HBV exposure. Because maternal HBV transmission early in life appears to be of minor impact and children are mostly infected later in infancy, HBV vaccination at birth is not indicated, while vaccination of all infants at 2-3 months of age with other paediatric vaccinations is the first priority. PMID- 7997493 TI - Hepatitis B in health workers in Italy. AB - In Italy, a vaccination campaign against hepatitis B was launched in 1985. It was strongly recommended for health care workers. Over the period 1986-91 the incidence rate of acute B hepatitis in the general population declined from 12/100,000 in 1986 to 5/100,000 in 1991. The corresponding figures among hospital workers were 42.5/100,000 (RR 3.5; 95% CI 2.55-4.92) in 1986 and 14.5/100,000 (RR 2.9; 95% CI 2.03-4.14) in 1991, respectively. The proportion of HBV cases with jaundice was about the same in the general population (77.6%) and in the health care staff (74.2%). Nearly 6% of hospital workers cases had completed the schedule of HBV vaccine. Despite the fact that vaccination against HBV has been strongly recommended for hospital workers, the incidence of infection in this job category has continued to be higher than that in the general population, probably as a consequence of poor vaccine coverage. These findings reiterate the need for aggressive vaccination programmes in hospital workers. PMID- 7997494 TI - A slow death or eternal life? Future directions for annual public health reports. AB - Several years after their reintroduction, district public health reports continue to face questions about purpose, content and evaluation. As public health embraces the wider vision of the World Health Organisation's 'Health for All' strategy, and the consequent need for collaboration with other sectors and participation with communities, there is a need for the reports to respond accordingly. This theme is explored in relation to the needs of the report's diverse audience, the type of local research required to make the report relevant and effective, and approaches to evaluation. A growing local research function has resource and training implications for Departments of Public Health. The demands of producing a report every year suggest that biennial publication of the main report, with other targeted products over the intervening period, would be a more realistic and effective option. PMID- 7997495 TI - The status and tasks of public health medicine in England in 1991 and 1993. AB - Two national postal surveys of directors of public health, the first in 1991 and the second in 1993, looked at the extent to which HC(88)64 had been implemented. Response rates for both exceeded 80%. In 1991 virtually all health authorities had, as required by the circular, appointed directors of public health and had annual health reports published. It took until 1993 for the requirement for collaborative work to be more firmly established. More work with FHSAs is now needed, together with effective use of extensive provider involvement, if HSG(93)56 is to be achieved. PMID- 7997496 TI - Public health medicine training and the NHS changes. AB - The current round of mergers between Health Authorities and Family Health Service Authorities (FHSAs), when set in the competitive context of markets, has profound implications for training in Public Health Medicine. This paper considers the phases in the management of change and the costs, benefits and principles for trainers, trainees and organisations as mergers take place. Particular emphasis is placed on understanding the motives of and learning from the change that is taking place. PMID- 7997497 TI - Patterns of injuries in athletes evaluated in an interdisciplinary clinic. AB - The pattern of sports injuries appears to be population-specific. The purpose of the present study is to describe 1750 injuries evaluated between April 1988 and April 1994 in our Olympic Training Center Interdisciplinary Sports Injury Clinic. Our patient population included elite and recreational athletes of both sexes between the ages of 7 and 71 years. Males comprised 73% of the patient population and approximately 80% of the injuries corresponded to the 10 to 29 age range. The most frequent sports in males were baseball (21.9%) and basketball (15.9%) and in females were track and field (17.1%) and gymnastics (15.1%). Most injuries (52%) were traumatic in nature, chronic (71.6%), and occurred during training sessions (57.4%). The most commonly affected anatomical areas were the knee (31.2%) and shoulder (15.5%). The most common diagnoses were tendinitis (25.4%), and first degree strains (11.8%) and sprains (9.3%). Finally, treatment strategies included medications (61.0%), physical therapy (48.9%), relative rest (35.7%), and home exercise programs (35.2%). The variety of musculoskeletal disorders seen in combination with the frequent use of conservative treatment confirms the importance of an interdisciplinary approach to sports injuries. PMID- 7997498 TI - Mesenteric cyst of lymphatic origin: a radiopathological correlation and case report. AB - Mesenteric cysts are uncommon abdominal masses in children. They occur most frequently in the small bowel mesentery and often contain chylous fluid. These cysts may be multilocular, grow to huge proportions and are believed to be caused by obstructed, malformed, ectopic lymphatic tissue. The patients' clinical presentations is dependent on cyst size, location and related complications such as partial or complete bowel obstruction, perforation, peritonitis, volvulus and malignant degeneration. Surgical resection is the treatment of choice. Ultrasound and CT are the most valuable modalities for evaluating mesenteric cysts. PMID- 7997500 TI - A newly designed partial subperiosteal implant and the classical design: a comparative study. AB - Seventy two partial subperiosteal implants were inserted in 52 patients. Thirty six of these implants had a classical design in which the submerged structure had thick primary and secondary connectors. Thirty six implants had a newly designed submerged structure consisting of long and thin primary connectors with grooves along their outer surfaces designed to stop or delay the downgrowth of epithelial mucosa. A six year evaluation revealed a 92.5% success of the newly designed implants and an 84% success for the classical design. A 10 year statistical projection revealed a 50% cumulative success for the classical design and a 92.5% success for the new design. PMID- 7997499 TI - Apgar score and infant mortality in Puerto Rico. AB - This study has as its objectives: 1) to examine the association between Apgar score and a set of demographic and sociodemographic variables so as to assess its usefulness as an indicator of the physical conditions of the newborn; 2) to determine if Apgar score in Puerto Rico is a good predictor of the newborn probability of surviving during his first year of life. For this purpose the 1990 live births and infant deaths data was utilized. The results indicate a direct relation between Apgar score with mother's schooling, father's occupation, and number of prenatal visits. Apgar score shows, also, an U curve type relationship with birthweight and gestational age, while it was found to be higher in private than in public hospitals. One of the most important findings was the strong association between infant mortality and Apgar score, even when the effect of other important independent variables such as birthweight and gestational age were held constant. These results demonstrate that, in spite of its criticisms Apgar score seems to be an excellent indicator of the newborn conditions at birth and a very good predictor of infant mortality in Puerto Rico. PMID- 7997501 TI - Radiographic estimation of intracuff pressure in mechanically ventilated patients. AB - We evaluated the usefulness of roentgenographic tracheal tube cuff shadow to tracheal wall diameter ratio (CTW ratio) and cuff minus tracheal diameter difference (C-T diameter) in estimating intracuff pressure (ICP) in intubated and mechanically ventilated patients. Seventy-one measurements of ICP, CTW ratio and C-T diameter were obtained from 20 mechanically ventilated male patients intubated with high volume low pressure cuffs in the surgical and medical intensive care units. The mean age was 61 years (range 30 to 83 years). ICP was measured by one observer, while CTW ratio and C-T diameter was measured by another observer. No significant relationship was seen between ICP and CTW ration (r = 0.092, p = 0.873), or between ICP and C-T diameter (r = 0.093, p = 0.42) by linear regression analysis. In conclusion, roentgenographic estimation of ICP by portable plain chest films in intensive care units was not found useful in this study. PMID- 7997502 TI - [Total quality approach and its application to the teaching-learning process]. PMID- 7997503 TI - [Quality: myth or reality. Towards an integral strategic quality approach]. PMID- 7997504 TI - [Total quality: implications to the continuous improvement of academic programs]. PMID- 7997505 TI - [Total quality management approach: implications for academic mangement]. PMID- 7997506 TI - Rads and grays--becquerels and curies. PMID- 7997507 TI - Molecular analysis of gamma-ray-induced mutations at the hprt locus in primary human skin fibroblasts by multiplex polymerase chain reaction. AB - A total of 153 hprt mutants (23 spontaneous, 130 gamma-ray-induced) of primary human skin fibroblasts were isolated and genetic alterations at the locus were studied by multiplex polymerase chain reaction (PCR). The analyses showed that 51% (66/130) of gamma-ray-induced genetic changes were large deletions, whereas the majority of spontaneous mutants (21/23) exhibited point mutations. The spectrum of large genetic alterations appeared to be dependent on dose in gamma ray-induced (1-4 Gy) mutations; mutants with complete loss of the hprt locus comprised 21 (3/14) or 39% (15/38) of clones isolated after irradiation with 1 or 4 Gy, respectively. The frequency of partial deletions was found to be higher in the mutants isolated from clones irradiated with 2 Gy (38%) than from those irradiated with 4 Gy (8%). Mapping of all intragenic deletion breakpoints exhibited a nonrandom distribution of breakpoints toward the 3' end of the hprt gene. PMID- 7997509 TI - More about cancer incidence in atomic bomb survivors: solid tumors, 1958-1987. PMID- 7997508 TI - Comments on "Updated analyses of combined mortality data for workers at the Hanford site, Oak Ridge National Laboratory, and Rocky Flats Weapons Plant" (Radiat. res. 136, 408-421, 1993) PMID- 7997510 TI - Are three forms of potentially lethal damage expressed after x irradiation by treatment with hypertonic solutions in chinese hamster V79 cells? AB - X rays have been shown to induce two forms of potentially lethal damage (PLD), "fast-repairing" PLD and "slowly repairing" PLD, whose repair is completed in 1 h and 4-6 h, respectively. In this study three modes of treatment with hypertonic solutions containing different NaCl concentrations for different durations (0.5 M for 30 min, 0.225 M for 4 h, 0.16 M for 16 h) were examined to determine which form of PLD is expressed under each condition. These three modes of treatment enhanced the cell-killing action of X rays on actively growing V79 cells due to fixation of PLD. The kinetics of recovery from PLD was assessed by delayed treatments with hypertonic solutions. Cells exposed to one of the three treatments (see above) had completed recovery times of 1, 4 and 8 h, respectively, suggesting the possibility that these three modes of treatment cause the expression of different forms of PLD. As has been reported, treatment with 0.5 M NaCl for 30 min expressed fast-repairing PLD. The independence of the PLD expressed by 0.225 M NaCl for 4 h from fast-repairing PLD expressed after 0.5 M NaCl for 30 min was shown by combined treatment with the two modes, which reduced survival to the level that would be reached if the two modes acted independently. The data on the recovery time and on the inhibition by 0.225 M NaCl of recovery from slowly repairing PLD in plateau-phase cells indicated that the PLD expressed after 0.225 M NaCl for 4 h may be related to slowly repairing PLD. The combined treatment of 0.16 M NaCl for 16 h with 0.225 M NaCl for 4 h indicated independent action, albeit incomplete, of the PLD expressed after 0.16 M NaCl for 16 h from slowly repairing PLD. We propose for the first time that "very slowly repairing" PLD is expressed after 0.16 M NaCl for 16 h in exponentially growing cells and that therefore three forms of PLD are expressed by hypertonic treatments after X irradiation. PMID- 7997511 TI - Mapping the end points of large deletions affecting the hprt locus in human peripheral blood cells and cell lines. AB - We have examined the extent of HPRT- total gene deletions in three mutant collections: spontaneous and X-ray-induced deletions in TK6 human B lymphoblasts, and HPRT- deletions arising in vivo in T cells. A set of 13 Xq26 STS markers surrounding hprt and spanning approximately 3.3 Mb was used. Each marker used was observed to be missing in at least one of the hprt deletion mutants analyzed. The largest deletion observed encompassed at least 3 Mb. Nine deletions extended outside of the mapped region in the centromeric direction (> 1.7 Mb). In contrast, only two telomeric deletions extended to marker 342R (1.26 Mb), and both exhibited slowed or limited cell growth. These data suggest the existence of a gene, within the vicinity of 342R, which establishes the telomeric limit of recoverable deletions. Most (25/41) X-ray-induced total gene deletion mutants exhibited marker loss, but only 1/8 of the spontaneous deletions encompassed any Xq26 markers (P = 0.0187). Furthermore, nearly half (3/8) of the spontaneous 3' total deletion breakpoints were within 14 kb of the hprt coding sequence. In contrast, 40/41 X-ray-induced HPRT- total deletions extended beyond this point (P = 0.011). Although the overall representation of total gene deletions in the in vivo spectrum is low, 4/5 encompass Xq26 markers flanking hprt. This pattern differs significantly from spontaneous HPRT- large deletions occurring in vitro (P = 0.032) but resembles the spectrum of X-ray-induced deletions. PMID- 7997512 TI - Determination of the radiobiologically hypoxic fraction in multicellular spheroids from data on the uptake of [3H]fluoromisonidazole. AB - Fluoromisonidazole [1-(2-nitroimidazolyl)-2-hydroxy-3-fluoropropane, FMISO] shows promise as a hypoxia imaging agent: it binds preferentially to anoxic cells in monolayers in vitro and accumulates in radiobiologically hypoxic tumors in vivo. The multicellular spheroid model was used to determine if the radiobiologically hypoxic fraction could be predicted from data on the uptake of FMISO. Chinese hamster V79-171b spheroids approximately 500 microns in diameter were exposed to 50 mM [3H]FMISO for 1 to 6 h under aerobic (5% CO2 in air), hypoxic (5% CO2, 5% O2, in N2) or anoxic (5% CO2 in N2) conditions and FMISO uptake was measured. Uptake in anoxic spheroids was similar to that in anoxic cell monolayers, while there was virtually no uptake in aerobic spheroids. A mathematical model was developed to calculate the radiobiologically hypoxic fraction in the hypoxic spheroids from the data on FMISO uptake. A radiobiologically hypoxic fraction of 15% was obtained, consistent with that determined from radiation survival assays (17%) and measurements of oxygen consumption (22%). We conclude that the rate of FMISO uptake in V79-171b spheroids correlates with the radiobiologically hypoxic fraction. Furthermore, the radiobiologically hypoxic fraction can be calculated from data on FMISO uptake if the dependence of FMISO uptake on oxygen concentration is known for a given tumor cell type. PMID- 7997513 TI - Clonogenic survival studies of human colon tumor cell lines in vitro: combined hyperthermia, 5-fluorouracil/leucovorin, carboplatin and tumor necrosis factor. AB - The responses of DLD-1 and HCT-15 human colon adenocarcinoma cells to hyperthermia, 5-fluorouracil (5-FU)/leucovorin, carboplatin and tumor necrosis factor-alpha, singly and in multiple combinations, were evaluated in clonogenic assays. The combination of hyperthermia with the lower dose combination resulted in a survival fraction of about 0.005 to 0.001 for both cell types, whereas estimated additive interactions alone would have resulted in a survival fraction of about 0.5 (DLD-1) or 0.05 (HCT-15). A survival fraction of 0.00001 or greater was observed when the higher dose levels were combined with hyperthermia, whereas additive interactions alone would have achieved a decrease of only 0.001 or 0.0001 in the surviving fraction. The combination of the three other modalities at either dose level under conditions of hyperthermia or normothermia achieved statistically significant apparently supra-additive losses of clonogenicity in HCT-15 cells; similar results were obtained with the lower dose level in DLD-1 cells. Our results suggest that human colon tumor cells are markedly sensitive to this combination of modalities when used at clinically achievable dose levels. PMID- 7997514 TI - Quantification of micro-regional heterogeneities in tumor oxygenation using intravascular HbO2 saturations. AB - Despite promising reports as to the relationship between tumor radiosensitivity and overall tumor oxygenation, little additional information has been forthcoming regarding the importance of localized variations in tumor oxygen distribution. The objectives of the current study were (1) to devise a strategy for sampling tumor HbO2 saturation distributions and (2) to compare intratumor heterogeneities in HbO2 profiles with intertumor variability to determine whether representative tumor oxygen profiles can be obtained from a limited tumor sample. Using murine KHT fibrosarcomas, maps of tumor intravascular HbO2 saturations were obtained using cryospectrophotometric techniques and without the use of anesthetics. Micro regions composed primarily of either high or low HbO2 vessels were observed in both peripheral and interior regions of the KHT tumors, although HbO2 levels were higher, on average, toward the periphery. To quantify intra- and intertumor heterogeneities in oxygen delivery, alternative HbO2 sampling protocols were evaluated in comparison to all-inclusive HbO2 maps for each tumor cross section. Since intratumor variations in HbO2 distributions were of the same order of magnitude as intertumor variations for tumors of a single tumor line, it is clear that tumor micro-regional physiology cannot be characterized adequately by a single regional sample. PMID- 7997515 TI - Risk cross sections and their application to risk estimation in the galactic cosmic-ray environment. AB - Radiation risk cross sections (i.e. risks per particle fluence) are discussed in the context of estimating the risk of radiation-induced cancer on long-term space flights from the galactic cosmic radiation outside the confines of the earth's magnetic field. Such quantities are useful for handling effects not seen after low-LET radiation. Since appropriate cross-section functions for cancer induction for each particle species are not yet available, the conventional quality factor is used as an approximation to obtain numerical results for risks of excess cancer mortality. Risks are obtained for seven of the most radiosensitive organs as determined by the ICRP [stomach, colon, lung, bone marrow (BFO), bladder, esophagus and breast], beneath 10 g/cm2 aluminum shielding at solar minimum. Spectra are obtained for excess relative risk for each cancer per LET interval by calculating the average fluence-LET spectrum for the organ and converting to risk by multiplying by a factor proportional to R gamma L Q(L) before integrating over L, the unrestricted LET. Here R gamma is the risk coefficient for low-LET radiation (excess relative mortality per Sv) for the particular organ in question. The total risks of excess cancer mortality obtained are 1.3 and 1.1% to female and male crew, respectively, for a 1-year exposure at solar minimum. Uncertainties in these values are estimated to range between factors of 4 and 15 and are dominated by the biological uncertainties in the risk coefficients for low-LET radiation and in the LET (or energy) dependence of the risk cross sections (as approximated by the quality factor). The direct substitution of appropriate risk cross sections will eventually circumvent entirely the need to calculate, measure or use absorbed dose, equivalent dose and quality factor for such a high-energy charged-particle environment. PMID- 7997516 TI - Radiosensitivity of testicular cells in the fetal mouse. AB - The effects of prenatal X irradiation on postnatal development of the CBA/P mouse testis was studied. At days 14, 15 and 18 post coitus pregnant female mice were exposed to single doses of X rays ranging from 0.25-1.5 Gy. Higher doses resulted in extensive loss of fetal mice. In the male offspring, at days 3 and 31 post partum, the numbers of gonocytes, type A spermatogonia and Sertoli cells per testis were determined using the disector method. Furthermore, after irradiation at day 15 post coitus, the numbers of Leydig cells, mesenchymal cells, macrophages, myoid cells, lymphatic endothelial cells, endothelial cells and perivascular cells per testis were also determined at days 3 and 31 post partum. At day 3 post partum, the number of germ cells was decreased after irradiation at days 14 and 15 post coitus. A D0 value of 0.7 Gy was determined for the radiosensitivity of the gonocytes at day 14 post coitus. A D0 value of 0.8 Gy was determined for the gonocytes at day 15 post coitus which, however, seems to be less accurate. No accurate D0 value could be determined for the gonocytes at day 18 post coitus. At day 31 post partum, the repopulation of the seminiferous epithelium as well as testis weights and tubular diameters were more affected by irradiation with increasing age of the mice at the time of irradiation. The percentage of tubular cross sections showing spermatids decreased with increasing dose after irradiation at days 15 and 18 post coitus, but not after irradiation at day 14 post coitus. Furthermore, in tubular cross sections showing spermatids, exposure of testes to 1.25 and 1.5 Gy at day 18 post coitus resulted in significantly lower numbers of spermatids per cross section when compared to those testes exposed to the same doses at day 15 post coitus. This indicates that the radiosensitivity of the gonocytes increases with fetal age. Prenatal irradiation did not cause significant changes in the numbers per testis of the Sertoli cells or the interstitial cell types. The present results indicate that, in the fetal mouse testis, the spermatogonial stem cells are more sensitive to X irradiation than in the adult testis, while Sertoli cells and interstitial cells are relatively resistant. PMID- 7997517 TI - Repair rate in mouse lung after clinically relevant radiation doses per fraction. AB - Data published previously have shown that repair of sublethal damage in mouse lung proceeds with two significantly different repair half-times of 0.4 h and 4.0 h and that the fast component has approximately four times more weight than the slow component. None of these data, however, were obtained after small dose fractions similar to those used in clinical radiotherapy. The purpose of the experiments presented here was to determine the half-time of the fast component only of repair in mouse lung after doses per fraction of 2.0 Gy. We irradiated the whole thoraces of mice with six equal doses of 2.09 Gy given at intervals ranging from 0 to 45 min. The dose was topped up 24 h later by a range of single doses designed to bring the response, i.e. breathing rate and death from pneumonitis, into the observable range. Data on breathing rate were converted into quantal response data. All data were analyzed by the linear-quadratic model that contains two rates of repair (H.D. Thames et al., Radiother, Oncol. 15, 49 53, 1989). The data showed that the repair rate is very rapid, giving a t1/2 ranging from 0.25 to 0.75 h for breathing rate and mortality, in agreement with our data published previously for higher dose fractions. There were no differences between the t1/2's obtained from the two assays of damage. These data indicate that the half-time of the fast component of repair in mouse lung is approximately 0.4 h after clinically relevant dose fractions. PMID- 7997518 TI - Cigarette use and the estimation of lung cancer attributable to radon in the United States. AB - Residential exposure to radioactive radon and its decay products has been estimated to account for 10-12% of all lung cancer deaths in the U.S. It has been difficult to evaluate fully the impact of cigarette smoking, the most important cause of lung cancer, on this estimate, because factors for patterns of tobacco use have not been included in the risk models, since risk models are derived from studies of underground miners exposed to radon and detailed data on smoking are limited. Lung cancer risk estimates for exposure to radon progeny in smoker and non-smoker populations are obtained by applying the same risk model to each population group, thereby assuming the joint effects of smoking and exposure to radon progeny are multiplicative. However, in miners, joint relative risks (RR) for the two exposures are most consistent with an intermediate relationship between multiplicative and additive, so that the present approach likely results in an overestimate of risk in smokers and an underestimate of risk in nonsmokers. Lubin et al. (National Institutes of Health Publication No. 94-3644, 1994) present an ad hoc approach for adjusting risk models to incorporate smoking status. The approach is based on the relative magnitude of the effects of radon progeny in smokers and nonsmokers and therefore may not be applicable to non miner populations if the proportion of smokers and the RR for smoking differ. We show that the modification can be derived explicitly by assuming an arithmetic mixture model for the joint RR for smoking and exposure to radon progeny. In this way, smoking parameters in the population of interest (the proportion of smokers and the RR of smoking) can be used directly to adjust radon progeny risk models and obtain risk estimates that are specific for smokers and nonsmokers. With an intermediate RR relationship for smoking and radon progeny, the attributable percentage of lung cancer deaths from residential radon may be twofold greater in non-smokers than in smokers. PMID- 7997519 TI - Pulse radiolysis study of vitamin K1 reduction in ethanolic solution. AB - A pulse radiolysis study of vitamin K1 reduction was carried out in argon saturated ethanolic solutions. The alpha-hydroxyethyl radicals CH3C.HOH (R.) and the solvated electrons (e-solv) reduce vitamin K1, leading to the semiquinone transient K1H.. This species, characterized by its absorption spectrum, decays by disproportionation and leads to the formation of the hydroquinone K1H2. The rate constants of the monoelectronic exchanges involved in this reduction have been determined. PMID- 7997520 TI - Free radical-induced double base lesions. AB - Evidence is presented for the formation of products in irradiated dinucleoside monophosphates in which both bases are damaged. The dinucleoside monophosphates d(GpT), d(GpC), d(TpG) and d(CpG) were X-irradiated in oxygenated aqueous solution. Product identification was by NMR spectroscopy. In products containing double base lesions, guanine is converted to 8-hydroxyguanine and the pyrimidine base is degraded to a formamido remnant. PMID- 7997521 TI - Dose-effect relationship for in vivo and in vitro induction of dicentric aberrations in blood lymphocytes of children. AB - Chromosome aberrations induced in vivo were studied in nine children 5-12 years old treated with total-body high-energy photon irradiation (pulsed exposure from a LINAC) for different types of malignant diseases. Dose-effect relationships were obtained for each child by taking blood at different times during exposure. In vitro dose-effect relationships for chromosome aberrations in children and adults were obtained by exposing blood under the same conditions as the children. Exposure in vivo and in vitro yielded similar linear-quadratic dose-effect relationships for dicentric aberrations. The response in vitro was slightly greater than in vivo, but the difference was not very large. It is concluded that the dose-effect relationship for dicentric chromosome aberrations obtained in vitro for adults can be used for biological dosimetry in irradiated children. Some of the children displayed a high number of "rogue cells" before exposure; this may be due to the malignant disease as it was not found in the healthy controls. PMID- 7997522 TI - Inhibition of radiation cataractogenesis by WR-77913. AB - The radioprotective drug S-3-amino-2-hydroxypropylphosphorothioic acid (WR-77913) has been tested as an inhibitor of radiation cataractogenesis. Animals treated with 15 Gy whole-head 137Cs gamma radiation developed mature cataracts 10-12 weeks after irradiation. Intraperitoneal pretreatment with 815 mg/kg WR-77913 30 min before irradiation delayed the development of cataracts; mature cataracts required 42 weeks for development. Doses as low as 350 mg/kg, substantially below the toxic range, resulted in graded but incomplete protection and a significant delay in the development of cataracts. Drug treatment combined with radiation doses of 12.5 or 10 Gy showed less pronounced protection. The optimum time of drug delivery was found to be between 30 min and 2 h before irradiation; protective action diminished if longer times were used or if the drug was given after irradiation. These results are discussed in relation to those obtained with other chemical radioprotective agents and in terms of possible mechanisms of the action of the drug. PMID- 7997523 TI - The practice of radiobiology in the radiologic sciences. AB - To effectively practice radiation protection, radiographers must understand the potential biologic effects of radiation. This article reviews the importance of a knowledge of radiobiology to the work of radiologic technologists. The author describes four specific biologic effects from radiation exposure--leukemia, thyroid cancer, breast cancer and fetal effects--and presents clinical examples that relate to current radiation protection practices and concerns. PMID- 7997524 TI - Helping patients overcome their fear of mammography. AB - Research shows that between 50% and 60% of U.S. women do not follow established guidelines on mammography. This article examines some of the reasons women cite for not undergoing the examination. These reasons include cost, absence of breast cancer symptoms and lack of family history of breast cancer. Women also express fear of breast compression, radiation and an unfavorable diagnosis. These fears are a challenge to the professional mammographer, because imaging an uncooperative or apprehensive patient may result in suboptimal films or repeats. This article suggests ways mammographers can help alleviate patient fears and establish a rapport that will make the examination a more pleasant and informative experience. PMID- 7997525 TI - The cost-effectiveness of clinical education. AB - Debate has continued for years regarding the cost-effectiveness of educating radiography students in a clinical environment. This article reviews the existing literature and examines the results of a recent survey to identify the advantages and disadvantages of educating radiography students in a health care facility's radiology department. Results of the study indicate that the benefits associated with educating radiography students in a clinical setting far outweigh the costs experienced by the health care facility. PMID- 7997526 TI - The x-ray's discovery and early uses. PMID- 7997527 TI - Why MQSA? Why now? PMID- 7997529 TI - Use questions to improve class discussion. PMID- 7997528 TI - Ionic vs. nonionic contrast media. PMID- 7997530 TI - Solving your darkroom problem. PMID- 7997531 TI - Mammography update. AB - The collected data show that the typical registered mammographer is female, 39 years old, passed the ARRT mammography exam on her first attempt, was trained on the job, had less than five years of experience in mammography at the time she took the examination, performs more than 20 mammographic exams per week, has participated in a mammography-specific seminar within the past year, and works at an ACR-accredited mammography facility. This information is designed to draw a picture of the typical mammographer, not to establish any type of standard qualifications for personnel who perform mammography. If you have specific questions about mammography registrants that were not answered by this article, please write to the ARRT. PMID- 7997532 TI - It's better to be on the train than under it. PMID- 7997533 TI - Imaging of the ovary and adnexa: clinical issues and applications of MR imaging. AB - Many if not most adnexal masses that are resected for suspicion of malignancy are benign, and the ratio of benign to malignant masses removed increases dramatically if asymptomatic women are screened. More specific diagnostic tests may reduce the rate of unnecessary surgery in these patients. Magnetic resonance (MR) imaging may play a role in evaluating women with problematic ultrasound diagnoses. Conventional and chemical shift MR imaging can allow specific diagnosis of dermoid cysts, pedunculated leiomyomas, ovarian fibromas, most endometriomas, and hydrosalpinx. Gadolinium-enhanced MR imaging allows identification of papillary projections and septa in ovarian neoplasms and differentiation of clot and debris from vascularized tissue. Results of available studies suggest that MR imaging of the female pelvis is cost-effective in selected patients and can be used to obviate surgery in some patients. MR imaging with the use of these techniques may allow more appropriate clinical decisions to be made in selected patients with complex adnexal disease. PMID- 7997534 TI - Early hepatocellular carcinoma: appearance at CT during arterial portography and CT arteriography with pathologic correlation. AB - PURPOSE: To use computed tomography (CT) during arterial portography (CTAP) and CT arteriography to compare the hemodynamic properties of early hepatocellular carcinoma (HCC) with those of small HCC. MATERIALS AND METHODS: Forty-four early HCCs (mean diameter, 1.5 cm) in 37 patients (26 men and 11 women aged 52-74 years; mean age, 59.2 years) were studied. CTAP was performed on 35 early HCCs, CT arteriography on 20, and both studies on 11. CTAP, CT arteriography, or both were performed on 90 small HCCs (mean diameter, 2.0 cm) in 57 patients (44 men and 13 women aged 48-71 years; mean age, 61 years). The findings for small HCC were compared with those for early HCC. RESULTS: CTAP depicted 23 early HCCs as hypoattenuating masses and 12 as isoattenuating. CT arteriography depicted 11 early HCCs as hypoattenuating masses, six as isoattenuating, and three as hyperattenuating. CTAP depicted 85 of 88 small HCCs as hypoattenuating masses and three as isoattenuating. CT arteriography depicted 13 of 14 small HCCs as hyperattenuating masses. CONCLUSION: CTAP, the standard of reference for the detection of small HCC, is not sensitive enough for the detection of early HCC. PMID- 7997535 TI - Hepatocellular carcinoma: CT appearance of parenchymal changes after percutaneous ethanol injection therapy. AB - PURPOSE: To evaluate the changes in surrounding liver parenchyma after treatment of hepatocellular carcinoma (HCC) and borderline malignant lesions with percutaneous ethanol injection (PEI). MATERIALS AND METHODS: The authors reviewed the findings at computed tomography (CT) and CT during arterial portography (CTAP) obtained before and after PEI therapy for 32 lesions in 26 patients with HCC or adenomatous hyperplasia. Two surgically resected specimens were also histologically examined. RESULTS: In 10 (77%) of 13 lesions, decreased portal vein-related enhancement indicative of reduced portal blood flow in the periphery of the tumor was found at CTAP. Mild atrophy (concave liver surface), segmental atrophy, and lobar atrophy were found in 40%, 17%, and 3%, respectively. Histologic examination of the resected specimens revealed organized thrombi in the peripheral portal vein in the surrounding liver. CONCLUSION: PEI may cause decreased portal blood flow and atrophy in the noncancerous liver parenchyma that surrounds the tumor being treated. PMID- 7997536 TI - Hepatocellular carcinoma: use of color Doppler US to evaluate response to treatment with percutaneous ethanol injection. AB - PURPOSE: To determine the usefulness of color Doppler ultrasound (US) in the evaluation of the response of hepatocellular carcinoma (HCC) to percutaneous ethanol injection (PEI). MATERIALS AND METHODS: Forty-one patients with 48 lesions 2-5 cm in diameter underwent color Doppler US before and after PEI. Computed tomography (CT), magnetic resonance (MR) imaging, and percutaneous biopsy were also performed to help establish the outcome of therapy. RESULTS: Before treatment, color signals with an arterial Doppler spectrum were seen in 44 of 48 lesions with a frequency shift of 0.51-4.11 kHz (mean, 1.65 kHz). After PEI, 37 of these lesions showed no color signal and were found to be necrotic at CT, MR imaging, and biopsy. In six of seven lesions containing residual tumor, pulsatile flow was still identified, although the frequency shift was significantly decreased (P = .01). CONCLUSION: Color Doppler US proved useful in the assessment of the therapeutic effect of PEI on HCC. PMID- 7997537 TI - Blueberry juice: preliminary evaluation as an oral contrast agent in gastrointestinal MR imaging. AB - PURPOSE: To evaluate the use of blueberry juice as an oral contrast agent in magnetic resonance (MR) imaging. MATERIALS AND METHODS: MR imaging of phantoms of blueberry juice and of manganese chloride solutions with different manganese concentrations were conducted. Patient trials were conducted to evaluate manganese blood levels and signal intensity changes on MR images of the abdomen. T1- and T2-weighted conventional spin-echo MR imaging was performed at various field strengths. Six radiologists graded image contrast; signal intensities were calculated. RESULTS: T1 and T2 relaxation curves for blueberry juice and manganese chloride showed similar signal intensity profiles as a function of manganese concentration. Blood concentrations of manganese were unchanged before and after an oral dose of blueberry juice that contained 18 mg of manganese. The results of patient studies indicated that the optimal oral dose of manganese in blueberry juice was 3-4 mg/dL. T1 and T2 shortening were apparent at field strengths of 0.2-1.5 T. CONCLUSION: At appropriate concentrations, blueberry juice has the potential to be an effective oral contrast agent for MR imaging. PMID- 7997538 TI - MR urography: technique and application. AB - PURPOSE: To evaluate a magnetic resonance (MR) technique for depicting the kidneys and urinary tract. MATERIALS AND METHODS: Fourteen patients with urinary tract obstruction and 20 without obstructions were examined with a modified, heavily T2-weighted fast spin-echo pulse sequence (MR urography). In addition, six healthy volunteers underwent modified MR urography with intravenous administration of furosemide and ureteral compression prior to imaging. RESULTS: MR urography provided high-resolution images of the kidneys and urinary tract in all patients with obstruction with intact collecting systems. Anatomic anomalies were depicted in two patients. Intraluminal neoplasia was well demonstrated in both obstructed and nonobstructed systems (n = 4). Furosemide-enhanced MR urography provided fine anatomic and functional detail of both the kidneys and urinary tract (n = 6). CONCLUSION: MR urography may provide an alternative to more conventional urinary tract imaging techniques. It does not require ionizing radiation or iodinated contrast material. When combined with furosemide and ureteral compression, MR urography provides fine detail and reflects function. PMID- 7997539 TI - Indeterminate adrenal mass in patients with cancer: evaluation at PET with 2-[F 18]-fluoro-2-deoxy-D-glucose. AB - PURPOSE: To evaluate the ability of positron emission tomography (PET) to characterize adrenal masses in patients with cancer. MATERIALS AND METHODS: Twenty-four adrenal masses (size range, 1.5-10.0 cm [mean, 2.8 cm]) in 20 patients (13 men and seven women) with cancer (lung [n = 10], colon [n = 3], lymphoma [n = 3], miscellaneous [n = 4]) were evaluated. PET was performed in fasting patients 45 minutes after infusion of 5-10 mCi (185-370 MBq) of 2 [fluorine-18]-fluoro-2-deoxy-D-glucose (FDG). PET images were correlated with findings at computed tomography (CT), surgery, and/or percutaneous biopsy. RESULTS: Fourteen adrenal masses were proved malignant at surgery (n = 4), biopsy (n = 7), or follow-up (n = 3). Ten lesions were proved benign at biopsy (n = 4) or follow-up CT (n = 6). PET helped correct differentiation of benign from malignant adrenal lesions in all patients. A statistically significant difference (P < .001) was seen between mean tumor-to-background ratios for malignant (mean, 7.4; range, 2.9-16.6; median, 6.9) versus benign (mean, 0.8; range, 0.2-1.2; median, 0.6) adrenal lesions. CONCLUSION: PET helped correct differentiation of benign from malignant adrenal lesions. PMID- 7997540 TI - Cervical carcinoma: determination of recurrent tumor extent versus radiation changes with MR imaging. AB - PURPOSE: To evaluate the effectiveness of magnetic resonance (MR) imaging for assessment of the present and extent of tumor recurrence as determined with pathologic and surgical findings. MATERIALS AND METHODS: MR findings were retrospectively examined in 37 patients with a history of cervical carcinoma. Inter- and intraobserver variability was analyzed. Surgical or pathologic results were acquired in 34 of these patients; the remaining three patients were clinically followed up for at least 4 years. RESULTS: MR imaging allowed correct detection of recurrent tumor in 18 of 21 patients who had histologically documented recurrence. It helped correctly exclude recurrent disease in 15 of 16 patients. Sensitivity and specificity for detection of recurrence was 86% and 94%, respectively. Good intra- and interobserver agreement was demonstrated. CONCLUSION: MR imaging is a useful modality for differentiation of recurrent cervical carcinoma from radiation changes. Determination of the extent of recurrence with MR imaging may offer clinical assistance in the selection of optimal therapy. PMID- 7997541 TI - Squamous cell carcinoma of the uterine cervix: radiation therapy for patients aged 70 years and older. AB - PURPOSE: To evaluate the usefulness of radiation therapy for elderly patients with squamous cell carcinoma of the uterine cervix. MATERIALS AND METHODS: Two hundred ninety-three patients with squamous cell carcinoma of the uterine cervix underwent external pelvic irradiation and three sessions of low-dose-rate intracavitary irradiation. One hundred twenty-six patients were aged 70 years or older (elderly group), and 167 patients were aged 69 years or younger (younger group). Survival rates, pattern of failure, local control rates, and complications for the two groups were compared. RESULTS: The 5-year, cause specific survival rates for the elderly group with stage I, II, III, or IV disease were 100%, 81%, 73%, and 54%, respectively. Corresponding rates for the younger group were 100%, 92%, 74%, and 32%. Differences in survival curves, patterns of failure, recurrence rates, and incidences of radiation complications for the two groups were not statistically significant. CONCLUSION: Age did not influence the effectiveness of radiation therapy for the elderly patients. PMID- 7997542 TI - Radiation therapy of external iliac lymph nodes with lateral pelvic portals: identification of patients at risk for inadequate regional coverage. AB - PURPOSE: To determine whether "standard" lateral pelvic radiation therapy portals provide adequate margins for treating the external iliac lymph nodes (EILNs). MATERIALS AND METHODS: With computed tomographic (CT) data and a computerized algorithm, the course of the EILN chain was reconstructed in 48 patients. The marginal distance between a consistently localized portion of the EILNs and the anterior field border that was placed at the front of the pubic symphysis was recorded for each patient. RESULTS: The EILNs were covered adequately in only 50% of both men and women. More adequate EILN margins were observed in (a) women older than 68 years, (b) women with small anteroposterior separations, (c) men older than 70 years, and (d) men and women with a low central obesity index. Less adequate margins were observed in men who were obese or men with large anteroposterior separations. In the study population, no correlation was observed for sex, race, or tumor site. CONCLUSION: The authors recommend portals that are designed specifically for patients rather than standard portals that may inadequately cover the intended targets. PMID- 7997543 TI - Hibernating myocardium versus scar: severity of irreversible decreased myocardial perfusion in prediction of tissue viability. AB - PURPOSE: To determine whether quantitation of the relative severity of decreased perfusion in irreversible defects on myocardial perfusion images enables differentiation of viable hibernating myocardium from scar. MATERIALS AND METHODS: In 145 patients with previous myocardial infarction, 1,252 regions with irreversible defects proved by means of rubidium-82 rest-stress imaging were analyzed for relative severity (percentage decrease in perfusion). Myocardial tissue viability was determined by means of positron emission tomography with fluorine-18 fluorodeoxyglucose (FDG). RESULTS: The relative decreases in Rb-82 uptake in the 1,252 regions were categorized into nine levels of severity (30% to > or = 70%) in 381 regions of hibernating myocardium and 871 regions of scar. The values of relative decreased perfusion in the irreversible defects alone did not enable differentiation of hibernating myocardium and scar (P = .61). CONCLUSION: The results show no relationship between the relative severity of irreversible perfusion defects and the ability to distinguish between hibernating myocardium and scar. PMID- 7997544 TI - Technical optimization of spiral CT for depiction of renal artery stenosis: in vitro analysis. AB - PURPOSE: To determine empirically the effect of scan parameters and postprocessing techniques on depiction accuracy of renal artery stenosis with spiral computed tomographic angiography. MATERIALS AND METHODS: Critical (85%) and noncritical (45%) stenoses in the coronal plane were modeled in vitro and scanned with 12 combinations of collimation (1, 2, or 3 mm), table increment (pitch = 1-2),2 and reconstruction interval (0.5 or 1.0 mm). Five test images were generated for each spiral scanning technique: multiplanar reformation (MPR), maximum-intensity projections (MIPs: coronal MIP [MIPcor], coronal MIP targeted to phantom vessel and surrounding fat [target MIPcor]), transaxial imaging, and transaxial MIP. RESULTS: With 3-mm collimation, critical stenosis was overestimated to the point of occlusion on MIPcor images and underestimated on MPR and target MIPcor images. A 0.5-mm reconstruction interval was marginally beneficial for 1- and 2-mm collimation, but noise was prohibitive with 1-mm collimation. CONCLUSION: Critical renal artery stenosis is best depicted with 2 mm collimation, 2-4-mm table increment, and 1-mm reconstruction interval. PMID- 7997545 TI - Circulatory alterations induced by intra-arterial injection of iodized oil and emulsions of iodized oil and doxorubicin: experimental study. AB - PURPOSE: To evaluate circulatory alterations induced by intra-arterial injection of iodized oil and emulsions of iodized oil with an anticancer drug. MATERIALS AND METHODS: The viscosities and stability were evaluated in arterial flow of iodized oil and the emulsions. Doppler ultrasound was used to quantify the embolic effect in the arteries of rabbits. The behavior of doxorubicin and iodized oil in the rat cremaster muscle was studied with videomicroscopy. RESULTS: The emulsions did not break up after injection, and the size of discontinuous-phase droplets did not change. The embolic effect did not correlate with viscosity. The thinnest water-in-oil emulsion had the lowest embolic effect and induced homogeneous distribution of iodized oil droplets in the arterial tree. CONCLUSION: Changes in the formulation of emulsions obtained with the same proportions of drug and iodized oil change the distribution of iodized oil in the arterial tree, the location at which the drug is released, and the embolic effect. PMID- 7997547 TI - The reducing stent: treatment for transjugular intrahepatic portosystemic shunt induced refractory hepatic encephalopathy and liver failure. AB - PURPOSE: To examine the efficacy of a stent device in reducing the diameter of transjugular intrahepatic portosystemic shunts (TIPS) in patients with progressive liver failure or with shunt-induced hepatic encephalopathy. MATERIALS AND METHODS: Seven patients with TIPS (four with severe hepatic encephalopathy, three with progressive liver failure) underwent transjugular implantation of a stent designed to reduce the flow through the original TIPS channel. RESULTS: Implantation of the reducing stent proceeded without complication. Duplex sonography showed that stent flow decreased by 41% +/- 18 (mean +/- standard deviation). The four patients with hepatic encephalopathy showed substantial improvement. Concentrations of plasma ammonium and serum bilirubin improved considerably. In contrast, functional impairment progressed in the three patients treated for liver failure. The patients soon died. CONCLUSION: With the limited experience of treating these seven patients, the authors suggest that shunt induced hepatic encephalopathy can be effectively treated with implantation of a reducing stent. Hepatic failure, however, is a deleterious complication that seems to be irreversible. PMID- 7997546 TI - Bilateral lower extremity US in the patient with unilateral symptoms of deep venous thrombosis: assessment of need. AB - PURPOSE: To assess the need for bilateral ultrasound (US) evaluation for lower extremity deep venous thrombosis (DVT) regardless of predisposing factors in patients with unilateral symptoms. MATERIALS AND METHODS: Two hundred six patients with unilateral lower extremity symptoms suggestive of DVT were evaluated prospectively for predisposing factors and symptoms. Bilateral examinations were performed in all patients, and the prevalences of US-diagnosed DVT in symptomatic and in asymptomatic extremities were determined. RESULTS: Thirty-seven of the 206 patients had DVT in the symptomatic extremity. Twenty five of these 37 patients had predisposing factors. No DVT was found in any asymptomatic extremity. Because compression US has a sensitivity and a specificity of greater than 90% for the diagnosis of DVT, these results were statistically significant (P < .001). CONCLUSION: Regardless of predisposing factors, US screening for DVT in the lower extremities should be limited to the symptomatic extremity in patients with unilateral symptoms. This would decrease scanning time and cost without a decline in the DVT detection rate. PMID- 7997548 TI - Breast arterial calcification: association with coronary artery disease. Work in progress. AB - PURPOSE: To assess the association between mammographically detected breast arterial calcification (BAC) and coronary artery disease (CAD) and diabetes mellitus (DM). MATERIALS AND METHODS: The records of 182 women (aged 39-92 years) who underwent both mammography and coronary arteriography were retrospectively reviewed to determine BAC, CAD, and DM status. RESULTS: For women aged less than 59 years (under-59 group) (n = 54), nearly all women with BAC (n = 8) had CAD (n = 7) and also had DM (n = 6). For this group, the positive predictive value of BAC for CAD was 0.88 and the negative predictive value was 0.65 (chi 2 = 7.7, P < .05). DM was a confounding variable. The positive predictive value of DM for CAD increased from 0.62 when BAC was absent to 1.00 when BAC was present (standard error of difference, .22; P < .10). No significant association between BAC and CAD was found for women aged 59 years and older (n = 128). CONCLUSION: BAC in women aged less than 59 years may indicate an additional risk factor for CAD, particularly in diabetic patients. PMID- 7997549 TI - Quality-oriented mass mammography screening. AB - PURPOSE: To demonstrate the ability of a mass mammography screening program to provide consistently high-quality mammography screening, while at the same time sustain a large volume of patients to keep the cost of mammography low. MATERIALS AND METHODS: A public-funded, mass mammography screening program, begun in 1988, is currently being conducted in five Canadian provinces. For the Screening Mammography Program of British Columbia, complete follow-up data are available for the first 57 months of operation. During that time, the program expanded from one center with five radiologist screeners to 14 centers with 30 radiologist screeners. There were 201,937 examinations performed on 128,325 women, 35% of whom were younger than 50 years. RESULTS: There were 802 cancers detected at an overall rate of 6.2 per 1,000 women (2.8 per 1,000 in women younger than 50 years and 8.1 per 1,000 in women older than 50 years). In the women younger than 50 years, 90 (72%) of the cancers were stage 0 or stage I, and the axillary lymph nodes were involved in 14 (11%). In the women 50 years or older, 496 (73%) of the cancers were stage 0 or stage 1, and the axillary lymph nodes were involved in 97 (14%). CONCLUSION: If quality is carefully controlled, the results of a mass screening program can be either maintained or improved. For both age groups, the prognostic characteristics are similar. PMID- 7997550 TI - Effects of a program to train radiologic technologists to identify abnormalities on mammograms. AB - PURPOSE: To assess whether radiologic technologists could be successfully trained to identify abnormalities on mammograms. MATERIALS AND METHODS: Eight radiologic technologists from two different institutions took a pretest, underwent an 8-hour training course followed by a period of preceptorship, and then took a posttest. Seven radiologists also took the pretest and posttest, which consisted of evaluating 1,238 two-view screening examinations, including 318 biopsy-proved cancers. RESULTS: Overall, technologists at institution 1 had lower sensitivity (78%) at the pretest, which improved at the posttest (90%). Technologists at institution 2 had lower specificity at the pretest (44%), which improved on the posttest (64%). Hypothetical pairing of radiologists and technologists with use of posttest results revealed an increase in sensitivity (median increase, 12% at institution 1 and 19% at institution 2). CONCLUSION: Formalized training successfully modified the technologists' skills. Radiologic technologists could be used to increase the number of breast cancers detected at screening mammography. PMID- 7997551 TI - The radiologist as a primary care extender. PMID- 7997552 TI - Clinical efficacy of mammographic screening in the elderly. AB - PURPOSE: To compare mammographic screening results for women aged 65 years and older (elderly group) with those for women aged 50-64 years (younger group). MATERIALS AND METHODS: Mammography was performed in 32,140 women aged 50 years and older (10,914 elderly, 21,226 younger). Parameters studied included demographic data, screening interpretations, disposition of abnormal interpretations, results of biopsies, and characteristics of breast cancers. RESULTS: The cancer detection rate is substantially higher in elderly women (9.2 per 1,000 women) than in younger women (5.7 per 1,000 women). The median size of cancers in elderly women is 11 mm (vs 12 mm in younger women). Axillary nodal status is 93% node negative in elderly women (vs 88% node negative in younger women). Cancer stage is earlier in elderly women than it is in younger women (84% stage 0 or 1 vs 75% stage 0 or 1). CONCLUSION: Mammographic screening is at least as effective in detecting cancers for which there is a favorable prognosis in women aged 65 years and older as it is in women aged 50-64 years. Because the efficacy of screening in younger-group women has already been proved, it may be inferred that screening also benefits elderly-group women. PMID- 7997554 TI - Bronchial dehiscence in lung transplantation: CT evaluation. AB - PURPOSE: To determine the signs of bronchial dehiscence on computed tomographic (CT) scans in a select subset of lung transplant recipients. MATERIALS AND METHODS: In 23 patients who underwent single or bilateral sequential lung transplantations, CT scans were obtained for suspected or known diagnosis of bronchial dehiscence. Dehiscence was identified at bronchoscopy in 17 of the 23 patients. In four patients, the dehiscence was bilateral, resulting in 21 anastomotic dehiscences. RESULTS: CT allowed identification of a bronchial defect in 100% of the bronchoscopically proved dehiscences but only one (5%) of the 18 bronchoscopically proved intact anastomoses. CT also demonstrated extraluminal air in 100% of the bronchoscopically proved dehiscences. Only a very small amount of extraluminal air (without associated bronchial defect) was identified on CT scans in the early postoperative period in four additional patients with bronchoscopically proved intact anastomoses. CONCLUSION: CT is an easily performed and well-tolerated technique that has a high degree of sensitivity and specificity for depicting bronchial dehiscence. PMID- 7997553 TI - Thoracic manifestations of Behcet syndrome: radiographic and CT findings in nine patients. AB - PURPOSE: To evaluate the radiographic and computed tomographic (CT) findings of patients with thoracic Behcet syndrome. MATERIALS AND METHODS: Chest radiographs and CT scans of nine patients with thoracic Behcet syndrome were retrospectively reviewed. Findings were compared. RESULTS: Radiographs of the nine patients showed mediastinal widening in five (56%), air-space consolidation in five (56%), and lung mass in three (33%). CT scans of the nine patients showed that mediastinal widening was due to thrombosis in four (44%) or narrowing of the superior vena cava in one [11%], which caused mediastinal edema; that air-space consolidation (seen on both radiographs and CT scans) was due to pulmonary hemorrhage or infarction in five (56%); and that lung mass was due to aneurysm of the right or left pulmonary artery in three (33%). In addition, CT scans showed hyperinflation in one patient. CONCLUSION: Chest radiographic findings of thoracic Behcet syndrome are variable and nonspecific. CT can be helpful in the assessment of the syndrome by showing thrombosis of the superior vena cava and characteristic aneurysms of the pulmonary arteries. PMID- 7997555 TI - Transplanted lungs: nodules following transbronchial biopsy. AB - PURPOSE: To determine how often nodules occur in lung allografts due to transbronchial biopsy and the temporal relationship between the development of these lesions and biopsy. MATERIALS AND METHODS: During 2 years, 141 computed tomographic (CT) studies and 324 transbronchial biopsies were performed in 40 patients who had undergone lung transplantation. CT images and chest radiographs were retrospectively evaluated for evidence of lung injury. RESULTS: Thirteen CT studies of 12 patients revealed transbronchial biopsy injury. Seven cavitary and nine solid nodules were seen a mean of 8.8 and 18.6 days after biopsy, respectively. Two nodules were detected prospectively on radiographs; seven, retrospectively. In two patients, nodules not seen on chest radiographs obtained immediately after biopsy were seen on radiographs obtained 8 and 12 days later. Fifteen lesions resolved. One lesion left a linear scar. CONCLUSION: Nodules that represent transbronchial biopsy lung injury are seen on CT images up to 1 month after biopsy and may not be evident on chest radiographs obtained immediately after biopsy. PMID- 7997556 TI - Trisomy 13 syndrome: prenatal US findings in a review of 33 cases. AB - PURPOSE: To determine the type and prevalence of prenatal ultrasound (US) findings in fetuses with trisomy 13. MATERIALS AND METHODS: Prenatal US findings in 33 consecutive fetuses with trisomy 13 and in 200 karyotypically normal fetuses were reviewed and compared. RESULTS: One or more abnormalities were found in 30 fetuses (91%). Major anomalies detected by means of US included holoprosencephaly (13 [39%]) or other central nervous system anomalies (19 [58%]), facial anomalies (15 [48%]), and renal (11 [33%]) and cardiac (16 [48%]) defects. Growth retardation was also present in 16 (48%). Echogenic chordae tendineae were seen in 10 (30%), which includes seven (39%) of 18 fetuses examined before 20 menstrual weeks (compared with four [2%] of 200 fetuses in the reference group [P < .001]). Other findings not generally associated with trisomy 13 but present in this series included a large cisterna magna (six [18%]), mild cerebral ventricular dilatation (three [9%]), nuchal thickening or cystic hygroma (seven [21%]), and a hypoplastic left side of the heart (seven [21%]). CONCLUSION: Prenatal US can help detect one or more anomalies in most fetuses with trisomy 13; thus, US finding can indicate whether karyotype should be tested. PMID- 7997558 TI - Normal maturing distal tibia and fibula: changes with age at MR imaging. AB - PURPOSE: To describe the normal appearance of the maturing distal tibia and fibula at magnetic resonance (MR) imaging. MATERIALS AND METHODS: The authors retrospectively studied 50 MR examinations of patients aged 2 months to 21 years, dividing them into six developmental groups according to the appearance of the distal tibia and fibula. Epiphyseal ossification, physeal closure, and the signal characteristics of physeal cartilage were evaluated. RESULTS: Distal tibial epiphyseal ossification and physeal closure both began anteromedially and usually occurred earlier than in the fibula. The tibial physis developed an anteromedial undulation (Kump hump) before closure; volume averaging at the Kump hump simulated premature closure. The cartilaginous epiphysis had a lower signal intensity than the physis on T2-weighted images. The physis was most conspicuous on gradient-recalled-echo and fat-suppressed spin-echo proton-density-weighted images. CONCLUSION: Developmental cartilaginous and bone changes in the distal tibia and fibula follow a definite pattern and are well seen at MR imaging. PMID- 7997557 TI - Colonic strictures in children with cystic fibrosis. AB - PURPOSE: To determine the radiographic, clinical, surgical, and histologic findings in children with cystic fibrosis who develop strictures of the colon. MATERIALS AND METHODS: Ten children (five boys, five girls; age range, 2.5-9.0 years; mean age, 5.5 years), who were treated at the practices of the authors, were retrospectively identified and their medical records reviewed. RESULTS: Radiographic manifestations of the colonic disease included mucosal irregularity and spiculation with nodular thickening of the colonic wall and loss of normal colonic haustration. Luminal narrowing involved long segments of the colon. Longitudinal shortening of the colon was also a prominent feature. The decrease in caliber of the bowel ranged from mild narrowing to complete occlusion of the lumen. Histologic examination revealed severe submucosal fibrosis and fatty infiltration with transmural extension of the fibrosis to involve the serosa in some cases. Unlike in Crohn disease, however, acute inflammatory changes were minimal or absent. CONCLUSION: Colonic stricture in children with cystic fibrosis is due to irreversible and frequently progressive narrowing of the colonic lumen. PMID- 7997559 TI - Splenic trauma: is follow-up CT of value? PMID- 7997560 TI - Nonsurgical placement of a nasolacrimal polyurethane stent. AB - PURPOSE: To describe the placement of a nasolacrimal polyurethane stent with a new introducer set and hook. MATERIALS AND METHODS: The authors designed a soft polyurethane stent, an introducer that does not require balloon dilation, and a hook that can remove a ball-tipped guide wire from the inferior nasal meatus under fluoroscopic guidance. The stent was placed in 51 lacrimal systems in 44 outpatients who had complete obstruction of the lacrimal sac or nasolacrimal duct. RESULTS: Stent placement was technically successful and well tolerated in 50 of 51 nasolacrimal systems. The procedure lasted an average of 16 minutes (range, 10-33 minutes). After stent placement, 47 of 50 eyes showed complete resolution of epiphora, and the other three showed partial resolution. During follow-up, no stents migrated, and one stent became blocked. The stent was reopened by means of forceful irrigation of saline solution through the superior punctum. CONCLUSION: Placing a polyurethane nasolacrimal stent by use of the new introducer and hook simplifies the technique, shortens operating time, reduces cost, and makes the procedure well tolerated by patients. PMID- 7997561 TI - Inferior petrosal sinus: imaging-anatomic correlation. AB - PURPOSE: To correlate computed tomographic (CT) or magnetic resonance (MR) images with dissections of normal inferior petrosal sinuses (IPS). MATERIALS AND METHODS: Postmortem dissection was performed in 12 individuals, one of whom had undergone CT and MR imaging 3 months before death. Seven patients underwent IPS venography, CT, and MR imaging. One hundred sixteen patients with normal IPS underwent MR imaging; 40, CT and MR imaging; and two, CT, MR imaging, and arteriography. RESULTS: Images showed that the IPS and basilar plexus formed conspicuous, enhanced structures that provide much of the border between the clivus and cerebrospinal fluid. Axial, cross-sectional IPS dimensions were as large as 9 x 16 mm. The larger sinuses were contained by deep grooves of bone that sometimes showed marked cortical thinning. Sixty-nine (39%) of the 175 individuals studied had markedly asymmetric IPS. CONCLUSION: CT and MR images showed that normal IPS and basilar plexus vary in size and are frequently asymmetric. This range of normal measurements and appearances should be taken into account before abnormalities in this region are diagnosed. PMID- 7997562 TI - The hippocampus in status epilepticus: demonstration of signal intensity and morphologic changes with sequential fast spin-echo MR imaging. AB - PURPOSE: To describe imaging findings in the hippocampus in status epilepticus with fast spin-echo (SE) magnetic resonance (MR) imaging. MATERIALS AND METHODS: Five patients with status epilepticus were examined with fast SE MR imaging, and the findings were correlated with neuropathologic observations of status epilepticus. RESULTS: One patient with diffuse bilateral hippocampal and amygdalal abnormal hyperintensity died. In three patients with hippocampal abnormal hyperintensity and enlargement, hyperintensity and enlargement, follow up fast SE MR images depicted decreased hyperintensity and swelling; one patient has remained seizure free at 6 months follow-up; a complex partial seizure disorder developed in two, and repeat images demonstrated hippocampal atrophy. CONCLUSION: T2-weighted fast SE MR images demonstrate reversible abnormal hyperintensity and swelling of the hippocampus and amygdala in patients with status epilepticus. Sequential fast SE MR imaging allows differentiation of this process from neoplasia and is useful in documentation of post-status epilepticus developments such as mesial temporal sclerosis. PMID- 7997563 TI - Technique and application of MR urography. PMID- 7997564 TI - MR imaging field strength: prospective evaluation of the diagnostic accuracy of MR for diagnosis of multiple sclerosis at 0.5 and 1.5 T. AB - PURPOSE: To compare the diagnostic efficacy of middle-field-strength and high field-strength magnetic resonance (MR) imaging in diagnosis of multiple sclerosis. MATERIALS AND METHODS: One hundred thirty-two patients with suspected multiple sclerosis underwent MR imaging at 0.5 and 1.5 T. Imaging parameters were identical except for band width optimization at middle field strength. Images were interpreted by radiologists expert in MR imaging who were blinded to diagnosis and field strength. The diagnosis of multiple sclerosis was made by experienced neurologists, and indeterminate cases and patients without clinical evidence of multiple sclerosis were followed up for 6 months to 1 year. RESULTS: There was no difference in accuracy, sensitivity, or specificity between scanners in the diagnosis of multiple sclerosis or white matter disease. Equal numbers of lesions were detected at both field strengths in all parts of the brain. Image quality was always good or adequate at middle field strength. CONCLUSION: Higher field strength does not confer higher accuracy in the diagnosis of multiple sclerosis with current-generation MR imagers. PMID- 7997565 TI - Amyotrophic lateral sclerosis: correlation of clinical and MR imaging findings. AB - PURPOSE: To determine the magnetic resonance (MR) imaging characteristics of amyotrophic lateral sclerosis (ALS) and to evaluate possible correlations between the disease severity and the MR imaging findings. MATERIALS AND METHODS: The authors retrospectively reviewed MR images of the head in 17 patients with ALS (14 men and three women) and 17 age-matched control subjects. The corticospinal tract (CST) was analyzed for the following features: size, signal intensity, and number of sections and regions in which the CST could be seen. RESULTS: Patients with ALS demonstrated sharp, well-defined, round, symmetric lesions that were hyperintense to gray matter within the CST. The lesions were best seen at the level of the middle or lower internal capsule on T2-weighted images. Visualization of the CST on proton-density-weighted images (which occurred in eight ALS patients) is the most reliable MR finding. Low signal intensity was identified within the motor cortex in six patients. Positive MR findings correlated with average or rapid progression of the disease. CONCLUSION: Increased signal intensity in the CST on proton-density-weighted MR images is diagnostic for motor neuron disease and correlates with the rate of disease progression. Subtle ALS changes can be differentiated from the normal CST. Low signal intensity in the motor cortex on T2-weighted images is a useful finding. PMID- 7997566 TI - Response of non-Hodgkin lymphoma to radiation therapy: early and long-term assessment with H-1 MR spectroscopic imaging. AB - PURPOSE: To determine whether proton magnetic resonance (MR) spectroscopic imaging is a sensitive technique for defining tumor extent and assessing response of cerebral lymphoma to therapy. MATERIALS AND METHODS: Four hydrogen-1 MR spectroscopic imaging studies were performed in a patient with non-Hodgkin lymphoma (NHL) before, during, and after radiation therapy and at follow-up at 33 months after diagnosis of the recurrence of disease. The patient had a single, large lesion in the brain and underwent hyperfractionated radiation therapy for 4 weeks. A series of MR images was also obtained. RESULTS: The pretreatment study showed a lesion with a distinct spectral pattern: marked elevation of choline and lipids and great reduction of creatine and N-acetylaspartate. During and after treatment, H-1 MR spectroscopic images depicted a progressive reduction of the abnormal choline and lipid signals. Thirty-three months after treatment, multiple section H-1 MR spectroscopic images showed normal spectral patterns in all sections examined. CONCLUSION: H-1 MR spectroscopy may contribute to the neuroradiologic evaluation of NHL and, in particular, may be useful in monitoring therapeutic response. PMID- 7997568 TI - The cause of pulsus tardus in arterial stenosis. PMID- 7997567 TI - Hemodialysis: relationship between signal intensity of the posterior pituitary gland at MR imaging and level of plasma antidiuretic hormone. AB - PURPOSE: To investigate the correlation between signal intensity of the posterior pituitary gland on magnetic resonance (MR) images and levels of plasma antidiuretic hormone (ADH) in patients undergoing hemodialysis. MATERIALS AND METHODS: The cases of 25 patients undergoing hemodialysis (15 men and 10 women, aged 24-75 years [mean, 51 years]) were prospectively evaluated. Laboratory testing and MR imaging were performed both before and after hemodialysis in 14 patients and only before hemodialysis in 11 patients. RESULTS: Before hemodialysis, nine patients (36%) had normal hyperintensity in the posterior pituitary gland, with almost normal plasma ADH levels and slightly elevated plasma osmolality. In six patients (24%) with less hyperintensity than is characteristic in the posterior pituitary gland, plasma ADH levels were slightly increased or normal. In 10 patients (40%) with an isointense posterior pituitary gland, plasma ADH and osmolality levels were evaluated. CONCLUSION: Elevated plasma osmolality may cause increased plasma ADH concentration and a lack of hyperintensity in the posterior pituitary gland at MR imaging. PMID- 7997569 TI - Flow-augmentation device for peripheral vascular Doppler US. AB - To augment venous blood flow at Doppler ultrasonography (US) of the extremities, a device comprising a blood pressure cuff connected to an external reservoir was tested. Constant and easily controlled pressure was delivered with each compression by the same operator performing US. In 10 patients (four men and six women, aged 54-86 years), discomfort was reduced compared with discomfort during manual compression, which requires two operators. PMID- 7997570 TI - Laser guidance system for CT-guided procedures. AB - In a phantom and in 37 patients, a simple laser guidance system for computed tomography (CT)-guided procedures used the software program of the CT scanner and a laser beam mounted on the CT gantry without need for additional software or components. The skin entry point and angulation of the target path were determined. Then the system projected the desired needle path (including compound angulation), allowing accurate needle placement in all cases, even in small lesions. PMID- 7997571 TI - Identification of vascular anatomy on sagittal scout MR images. PMID- 7997572 TI - Reporting "missed" radiologic diagnoses. PMID- 7997573 TI - Reporting "missed" radiologic diagnoses. PMID- 7997574 TI - Reporting "missed" radiologic diagnoses. PMID- 7997575 TI - Treatment of adverse contrast media reaction. PMID- 7997576 TI - Location of the pyramidal tract. PMID- 7997577 TI - Walter B. Cannon, MD. PMID- 7997578 TI - How U.S. radiologists use their professional time: factors that affect work activity and retirement plans. AB - PURPOSE: To determine what demographic, professional, and practice characteristics are related to the amount of time radiologists work per week, to their allocation of time among professional activities, and to their plans for retirement. MATERIALS AND METHODS: The American College of Radiology surveyed 2,804 radiologists and nuclear medicine specialists. Means and percentiles were calculated for the radiologists' number of hours and days worked per week, number of weeks away, percentage allocation of time, and retirement intentions. Multiple linear and logistic regression analyses were performed. RESULTS: Full-time, post training radiologists worked a mean of 50 hours per week. Radiologists spent 2 weeks on professional education and 4.4 weeks on vacation each year. On average, 68% of professional time was spent on hospital patient care; 18%, on office patient care; 7%, on teaching and research; and 5% on administration. Forty-one percent of radiologists planned to eventually work part-time; 47% intended to retire fully. CONCLUSION: These data will provide an important baseline for modeling the future size of the radiologist workforce and for assessing changes in the ways radiologists use their time and plan their futures. PMID- 7997579 TI - Acute vertebral collapse: CT findings in benign and malignant nontraumatic cases. AB - PURPOSE: The value of computed tomography (CT) for differentiating benign from malignant causes of nontraumatic acute vertebral collapse (AVC) (associated with pain of less than 3 months duration) was evaluated. MATERIALS AND METHODS: The CT findings of 34 benign (osteoporotic) and 32 malignant (metastatic or myelomatous) nontraumatic AVCs were compared. RESULTS: The following CT findings were significantly more frequent in benign AVCs: cortical fractures of the vertebral body without cortical bone destruction, retropulsion of a bone fragment of the posterior cortex of the vertebral body into the spinal canal, fracture lines within the cancellous bone of the vertebral body, an intravertebral vacuum phenomenon, and a thin diffuse paraspinal soft-tissue mass (PSTM). The following CT findings were significantly more frequent in malignant AVCs: destruction of the anterolateral or posterior cortical bone of the vertebral body, destruction of the cancellous bone of the vertebral body, destruction of a vertebral pedicle, a focal PSTM, and an epidural mass. CONCLUSION: CT can help distinguish benign from malignant causes of nontraumatic AVC. PMID- 7997580 TI - Qualifying examinations: are they a measure of competence? PMID- 7997581 TI - Thoracolumbar burst fractures: evaluation with MR imaging. AB - PURPOSE: To determine the frequency of posterior ligamentous injury that occurs in patients with thoracolumbar burst fractures and to correlate ligamentous disruption with radiographic appearance. MATERIALS AND METHODS: Magnetic resonance (MR) imaging examinations of 21 patients with 25 thoracolumbar burst fractures were retrospectively evaluated to determine spinal ligament integrity. Radiographic and computed tomographic (CT) examinations were evaluated for interpediculate widening, midsagittal canal narrowing, posterior element fractures, and kyphosis; a radiographic assessment of posterior ligamentous integrity was made. These findings were then correlated with the status of the spinal ligaments. RESULTS: The patients were divided into two groups on the basis of the status of their supraspinous ligament (SSL). Six patients had disrupted SSLs, and 15 had intact SSLs. Radiographic and CT findings did not correlate with supraspinous ligament disruption. Radiographic indicators of posterior ligamentous disruption were present in only 33% of patients with SSL disruption. CONCLUSION: SSL disruption is a frequent occurrence in patients with burst fractures. No radiographic features of burst fractures correlate with SSL disruption, and radiographic signs of posterior ligamentous disruption are insensitive. PMID- 7997582 TI - Trabecular texture analysis of CT images in the relationship with spinal fracture. AB - PURPOSE: To evaluate age-related changes in trabecular texture and bone mineral density (BMD) and to determine the usefulness of texture analysis in the assessment of the risk of fracture. MATERIALS AND METHODS: The vertebral trabecular BMD was measured in 209 women aged 18-86 years. Run length analysis was applied to computed tomographic images obtained with 2-mm section thickness. The width of the trabecula (T-texture) and the width of the intertrabecular space (I-texture) were calculated. RESULTS: I-texture significantly increased with age in women 50 years of age or older (P < .0001). Women with fracture had significantly lower BMD (P < .0001 at 60-69 years, P < .05 at 70-79 years) and significantly higher I-texture (P < .05 at 60-69 years, P < .01 at 70-79 years). For fracture risk, BMD had the highest sensitivity and I-texture had the highest specificity in women aged 60-69 years; I-texture had the highest sensitivity and specificity in women aged 70-79 years. CONCLUSION: Texture analysis was helpful in the assessment of fracture risk, especially in elderly women. PMID- 7997583 TI - Ulnar collateral ligament: differentiation of displaced and nondisplaced tears with US. AB - PURPOSE: To determine the usefulness of ultrasound (US) in the differentiation of displaced and nondisplaced tears of the ulnar collateral ligament (UCL). MATERIALS AND METHODS: A 7.5-10-MHz linear-array transducer was used to examine 69 patients in whom a UCL tear was suspected, 43 of whom also underwent surgery. The US findings were compared with those obtained at surgery. RESULTS: Results of US corresponded to results of surgery in 37 of 43 patients. Findings were false positive in six patients. Twenty-six patients were treated conservatively with thumb casts. These patients showed stability and free range of motion at the first metacarpophalangeal joint at clinical follow-up (9-13 months). CONCLUSION: Sonography is useful for evaluating nondisplaced and retracted tears of the UCL and determining the need for surgery. PMID- 7997584 TI - Ulnar collateral ligament: differentiation of displaced and nondisplaced tears with US and MR imaging. AB - PURPOSE: To compare the usefulness of ultrasound (US) and magnetic resonance (MR) imaging in the differentiation of displaced and nondisplaced tears of the ulnar collateral ligament (UCL). MATERIALS AND METHODS: Seventeen patients (eight female and nine male, aged 14-70 years) with clinically diagnosed tears underwent examination with US and MR imaging. T1-weighted, spin-echo (SE) and T2-weighted, turbo SE sequences were used. MR and US findings were compared with those of surgery. Normal UCLs in 21 volunteers were also examined with MR imaging. RESULTS: The results of US were correct in 15 patients, but displaced and nondisplaced ruptures were misinterpreted in two patients (sensitivity, 88%; specificity, 83% for displaced, 91% for nondisplaced). Sensitivity and specificity were both 100% for MR imaging. The T2-weighted sequence was more useful because the normal UCL is rarely homogeneously hypointense. CONCLUSION: MR imaging is better than US, but both methods are useful in the evaluation of the torn UCL. PMID- 7997585 TI - Hip arthroplasty: the role of plain radiographs in outpatient management. AB - PURPOSE: To determine whether findings on plain radiographs alter clinical care in outpatient management after hip arthroplasty. MATERIALS AND METHODS: From June 1, 1993, through February 28, 1994, one arthroplasty surgeon saw 148 outpatients (age range, 15-86 years) after hip arthroplasty (163 prostheses). The surgeon made decisions about clinical management before he reviewed the plain hip radiographs. After he reviewed the radiographs, he recorded any changes in the management plan. RESULTS: In only one case did the radiographic findings change patient treatment. The prosthesis in this relatively asymptomatic patient had been in place for over 9 years and appeared clinically to be functioning well, but radiographs demonstrated aggressive granulomatosis. Therefore, the patient underwent revision arthroplasty. In the remaining 147 patients, radiographic findings had no impact on clinical management. CONCLUSION: Radiographic evaluation may be most beneficial in patients with hip prostheses that have been in place for many years to rule out asymptomatic bone loss due to aggressive granulomatosis. PMID- 7997586 TI - Broadband ultrasound attenuation in the diagnosis of osteoporosis: correlation with osteodensitometry and fracture. AB - PURPOSE: To evaluate the usefulness of broadband ultrasound attenuation in the prediction of osteoporosis. MATERIALS AND METHODS: Broadband ultrasound attenuation measurements of the calcaneus and dual x-ray absorptiometry (DXA) measurements of the lumbar spine and the femoral neck were obtained in 400 patients (295 female and 105 male), 135 of whom were classified as having osteoporosis. Correlation coefficients between broadband ultrasound attenuation and DXA were calculated. RESULTS: Patients with osteoporosis showed a statistically significant decrease in broadband ultrasound attenuation compared with healthy patients (59.7 dB/MHz +/- 1.3 [standard deviation] vs 75.1 dB/MHz +/ 0.8). Broadband ultrasound attenuation correlated statistically significantly with vertebral bone density (r = .49) and femoral neck density (r = .52). At a broadband ultrasound attenuation index of 64 dB/MHz, the sensitivity and specificity were both 85% for patients with osteoporotic fractures. CONCLUSION: Broadband ultrasound attenuation can be used to help differentiate between patients with osteoporosis and healthy patients and seems to be useful in the prediction of fracture risk. PMID- 7997587 TI - Helical CT during arterial portography: optimization of contrast enhancement and scanning parameters. AB - PURPOSE: To determine the optimal scanning parameters for helical computed tomography during arterial portography (CTAP) of the liver. MATERIALS AND METHODS: Single- and double-helix CTAP were performed in 11 and 20 adult patients, respectively, with 200 mL of contrast material (300 mg of iodine per milliliter) injected at a rate of 3 mL/sec via the superior mesenteric artery. Scanning delays were adjusted for single-helix CTAP so the last scan was obtained at 66 seconds. Delays were adjusted for double-helix CTAP so the last scan during the first helix (CTAP-1) was obtained 10 seconds before the end of the injection at 56 seconds and the first scan during the second helix (CTAP-2) was obtained at the end of the injection at 66 seconds. RESULTS: Single-helix CTAP scans were of poor quality owing to multiple perfusion abnormalities. Lesion detection for double-helix CTAP-1 was 93.2% and was 100% for CTAP-2, and CTAP-2 scans had significantly fewer perfusion abnormalities. CONCLUSION: A scanning delay of 60 66 seconds appears to be optimal. The CTAP-1 scans showed no useful information and need not be acquired. PMID- 7997588 TI - Transient splenic inhomogeneity with contrast-enhanced CT: mechanism and effect of liver disease. AB - PURPOSE: To use computed tomography (CT) and functional imaging to characterize the physiologic processes that result in transient splenic inhomogeneity during contrast material enhancement and determine their value in detection of diffuse liver disease. MATERIALS AND METHODS: CT scan data from nine control patients and 13 patients with diffuse liver disease were used to create functional images that displayed splenic perfusion and time to peak enhancement. A pixel-by-pixel analysis was used to create these images. RESULTS: Areas of early enhancement demonstrated higher perfusion and vice versa. In patients with liver disease, splenic perfusion values fell from 1.44 to 1.22 mL/min/mL in the areas that showed early enhancement and 1.24 to 0.89 mL/min/mL in the areas that showed late enhancement. As splenic perfusion values fell, the size of the regions that showed late enhancement increased. CONCLUSION: The combination of functional images and CT data has clarified the mechanism by which transient splenic inhomogeneity occurs and is of potential value in the detection of diffuse liver disease. PMID- 7997589 TI - Splenic trauma: value of follow-up CT. AB - PURPOSE: To determine the value of follow-up computed tomography (CT) after expectant treatment in patients with clinically stable blunt splenic trauma. MATERIALS AND METHODS: Medical records and CT studies for 42 patients were reviewed, and injuries were graded on a scale of 1-6. Patients were divided into three groups: stable patients with no follow-up CT (group 1, n = 14), stable patients with follow-up CT (group 2, n = 22), and symptomatic patients with follow-up (group 3, n = 6). Serial hemoglobin values and clinical findings at follow-up CT were reviewed. RESULTS: All patients in groups 1 and 2 remained clinically stable with good outcomes. In group 3, follow-up CT scans demonstrated worsening condition in four patients (67%), and three of the four had poor outcomes. CONCLUSION: Follow-up CT may be unnecessary in patients with clinically stable splenic trauma. PMID- 7997590 TI - Case #5. Adenoid cystic carcinoma. PMID- 7997591 TI - Alter egos. PMID- 7997592 TI - Pay sharp attention to safe use of contaminated objects. PMID- 7997593 TI - Don't forget infection control in the dental lab. PMID- 7997594 TI - Respiratory medications. PMID- 7997595 TI - Get out of a treatment rut with individualized therapy. PMID- 7997596 TI - Self-regulation requires your immediate attention. PMID- 7997597 TI - Case #7. Adenomatoid odontogenic tumor. PMID- 7997598 TI - A cancerous epidemic. PMID- 7997599 TI - Family ties may be a link to periodontal disease. PMID- 7997600 TI - From operatory to office. PMID- 7997601 TI - Sterility assurance can ensure instrument safety. PMID- 7997602 TI - Protection is priority in protocol. PMID- 7997603 TI - [Gadolinium-DTPA combined with a fat suppression technique in studies with magnetic resonance at 0.5 T in soft-tissue neoplasms]. AB - Combination of fat suppression techniques with intravenous paramagnetic contrast administration is usually performed using high-field MR systems. We combined a modified three-point Dixon technique for fat suppression with gadolinium-DTPA administration in the investigation of soft tissue neoplasms at 0.5 T. Nineteen patients with 21 neoplasms (14 primary malignant, 2 metastatic, 5 benign tumors) were examined. Examination protocol included unenhanced SE T1, PD and T2-weighted images. After the intravenous administration of gadolinium-DTPA (0.1 mmol/kg), a modified three-point Dixon technique provided three image sets, i.e., conventional T1-weighted SE images, fat-suppressed T1-weighted images and water suppressed T1-weighted images. Two observers evaluated the lesions for conspicuity and size in three image groups: unenhanced T1-, PD and T2-weighted images, enhanced conventional T1-weighted images, enhanced T1-weighted images with fat suppression. Ten lesions showed greater conspicuity on enhanced fat suppressed images than on unenhanced T1-, PD and T2- and enhanced conventional T1 weighted images. In 16 cases lesions were more conspicuous on enhanced water images than on conventional enhanced T1 images. Ten tumors exhibited a larger size (difference exceeding 20%) on enhanced fat-suppressed images. The combination of gadolinium with the modified Dixon technique improves the demonstration of soft tissue neoplasms at 0.5 T and allows lesion size to be measured more accurately. PMID- 7997604 TI - [Ultrasound densitometry and the index of Jhamaria in the diagnosis of senile osteoporosis]. AB - Over 90% of the calcaneum is made of trabecular bone, whose turnover is high and which is therefore very sensitive to bone metabolism changes. Thus, we evaluated the mineral content of the calcaneum with the semiquantitative Jhamaria index adapted by Aggarwal et al. (1986) and ultrasound measurements. With the latter method, broadband ultrasound attenuation (BUA) values were calculated, which indicate ultrasound signal breadth reduction when passing through the bone. The two techniques were used to examine 99 women, whose age ranged 65-79 years, referred for dorsolumbar pain and suspected senile osteoporosis. This condition was diagnosed with dorsolumbar spine radiographs and considering as osteoporotic only the patients with one or more vertebral collapses. Thus, any other cause of osteopenia was excluded with bone metabolism serourinary indices. The two groups of patients thus obtained (group A: 42 osteoporotic women with vertebral collapse and group B: 57 osteoporotic women with no vertebral collapse) exhibited significantly different Jhamaria index and BUA values (group A: 2.5 +/- 0.9, B: 3.7 +/- 0.96, A: 46.3 +/- 13.6, B: 60.2 +/- 15.6) (p < 0.001). The diagnostic accuracy of calcaneal BUA and Jhamaria indices, in the two groups, was 85.7% and 81%, respectively. The analysis of the mean values showed no significant correlation between BUA and Jhamaria index in the group of patients with vertebral collapse. On the contrary, the correlation of the two indices in the group of patients with no vertebral collapse exhibited slight statistical significance (r = 0.38). To conclude, on the basis of our results the calcaneum is confirmed as a reliable peripheral index of vertebral BMC and ultrasound measurements are suggested as a simple noninvasive method which can be used to diagnose senile osteoporosis. PMID- 7997605 TI - [Evaluation of rheumatoid arthritis of the knee with Doppler color]. AB - Color-Doppler US was used to study the vascularization of the synovial membrane and of the periarticular tissues of the knee in 14 normal subjects and 15 patients with active rheumatoid arthritis. The normal subjects exhibited few spot signals within the connectival spaces surrounding the knee and adjacent to the femoral condyles and to the tibial plates. The signals were mostly arterial and impedance was high because of the absence of inversion of diastole. A hypervascular pattern was detected in 13/15 patients with rheumatoid arthritis as a result of hyperemia associated with inflammation and synovial neoangiogenesis. In these patients, the signals came mostly from the synovial pannus and the soft tissues surrounding the joint. Spectral analysis detected both venous and arterial waveforms with lower resistance than normal (resistive index ranging 0.65 to 0.76). After local treatment, both venous and low-impedance arterial signals were no longer detectable in 4/9 patients with clinical remission. In conclusion, color-Doppler US can support gray-scale US in the assessment of joint inflammation in rheumatoid arthritis patients. Vascular findings seem to correlate well with local symptoms. Color-Doppler US could make a useful tool for monitoring the clinical activity of the disease in selected joints. PMID- 7997606 TI - [Ultrasonographic findings in Osgood-Schlatter disease]. AB - The Osgood-Schlatter disease affects the patellar tendon in its attachment to the tibial tuberosity. It is quite frequent in adolescents, especially in young males practising sports. Its diagnosis is mainly clinical. The findings of tenderness and focal swelling of the tibial tuberosity are typical of this condition. The Osgood-Schlatter disease can damage bone, cartilage, tendon and serous bursa. US yields complete information on the involvement of these structures. High resolution US of the knee was performed on 70 patients with clinically suspected Osgood-Schlatter disease. More or less apparent cartilage swelling was demonstrated in 100% of our patients, tibial tuberosity fragmentation in 75%, diffuse thickening of the patellar tendon, at times inhomogeneous, in 22% and finally bursitis of the infrapatellar bursa was demonstrated in 17% of our patients. US provides complete information on the involvement of the tibial tuberosity and of the surrounding soft tissues, thus proving to be a simple and reliable method to diagnose the Osgood-Schlatter disease. Moreover, US is suitable for the periodical follow-up of disease course. PMID- 7997607 TI - [Ultrasonographic characteristics of lipoma of the soft tissues]. AB - This study includes 72 subjects with 90 soft tissue lipomas examined with high resolution US. Forty-one lipomas were found in subcutaneous fat tissue, 29 in superficial muscles, 1 in the inguinal channed and 1 in the retroperitoneum. All the lesions were studied for: site, position in the body, number, shape, outline, size, echotexture, echogenicity and US beam transmission beyond the lesion. Sixty seven lipomas were slightly ovalar (93%), 53 had regular margins (73.6%) and 21 exhibited a poorly- or well-defined capsule (29.2%). Twenty-two per cent of lipomas was homogeneous, 54.2% was slightly inhomogeneous and the extant 23.6% was inhomogeneous. Forty-five lesions were hypoechoic (62.5%), 13 hyperechoic (18.1%), 10 isoechoic (13.9%) and 4 exhibited a mixed echostructure (5.5%). In 24 cases (33.3%) sound was transmitted better through lipoma than through surrounding soft tissues. Posterior US beam attenuation was observed in one case (1.4%). Fifty-one lipomas (70.9%) exhibited the typical "striped" pattern, i.e., inner hyperechoic bands parallel to the skin. The clinical diagnosis of lipoma is based on patients' clinical history and on the palpation of a soft, well-defined and mobile mass. The US findings of an ovalar, well-defined, sometimes capsulated and, most important, "striped" mass, suggest the diagnosis of lipoma. Indeed, in our opinion, this pattern is characteristic of lipoma and represents the US appearance of its fibrous stroma. Therefore, we recommend US as the first-step method in the study of lipomas. PMID- 7997608 TI - [Reconstruction of the anterior cruciate ligament with patellar tendon. Comparison between magnetic resonance and computerized tomography]. AB - CT and MR potentials were compared in 30 patients submitted to anterior cruciate ligament reconstruction using the patellar tendon. In each patient the clinical data were correlated with the following radiologic parameters: the course of the tibial and femoral tunnels, their intraarticular outlet sites and their shape, the shape of the intercondylar notch and of the medial wall of the lateral femoral condyle and, finally, the shape of the graft and of the synovia. The intraarticular outlet site of the tibial tunnel was studied on the sagittal or transverse planes. In the former case the distance from the anterior tibial edge was considered, together with its relationship to sagittal tibial depth. The intraarticular outlet site of the femoral tunnel which was studied on sagittal and coronal MR planes was determined at CT by calculating its distance, i.e., the number of scans, from the intercondylar notch and from the posterior edge of the femoral condyle. MRI yielded better results thanks to its multiplanarity, but CT proved superior in defining size and shape of the bone outlets, the presence of bone chips (sometimes responsible for synovial reaction), the shape of the intercondylar notch and of the medial wall of the lateral condyle. As regards graft visualization, both CT and MRI yielded satisfying results in most cases. Nevertheless, MR potentials appeared superior thanks to its capabilities in demonstrating the graft in its full length and in differentiating it from surrounding synovial reaction. PMID- 7997609 TI - [Preoperative ultrasonographic measurement of melanoma thickness with 20 MHz probe]. AB - The authors report on the preoperative evaluation of melanoma thickness with very high frequency US probes (20 MHz). Thirty patients with clinical suspicion of melanoma were examined preoperatively with US. The high quality of the images obtained with 20-MHz US probes allowed the lesions involving the superficial derma or, in more advanced cases, all derma, to be demonstrated and tumor thickness to be measured accurately. The latter is a major prognostic factor and indeed Breslow's classification is based on tumor thickness. The preoperative US study of melanoma thickness allows the surgeon to plan excision depth, which is necessary for accurate and safe tumor resection, that is, whose margins are proportionate to melanoma thickness. In the 30 patients submitted to preoperative US measurements of tumor thickness, US and histologic findings were in agreement. US overestimated melanoma thickness by 7 to 11%, which however had no impact on prognosis and surgical planning. While US can differentiate melanomas from other types of benign or malignant pigmented skin lesions such as blue nevus, pigmented basalioma or pigmented seborroic cheraosis, no unquestionable US signs have been found yet to differentiate melanoma from nevus, which makes US useless for the differential diagnosis. Nonetheless, surgeons can use preoperative US to adapt the exeresis of melanoma to its actual severity and to reduce scars to a minimum. Possible skin metastases can also be detected by US and thus removed. PMID- 7997610 TI - [Comparative evaluation of 2 non-ionic contrast media, iopentol (350 mgI/ml) and iopamidol (370 mgI/ml) in coronary angiography]. AB - This randomized double-blind comparative study was designed to investigate the safety and efficacy of a new nonionic monomeric contrast agent, Iopentol 350 mgI/ml, versus a nonionic monomeric contrast agent currently used, Iopamidol 370 mgI/ml, in cardioangiography. Blood pressure, heart rate, end-diastolic left ventricular and mean aortic pressure, ECG, adverse reactions and discomfort were the safety variables recorded; technical adequacy and diagnostic yield were the efficacy variables recorded. A hundred patients entered the trial and were subdivided into two groups of 50 patients each; all of them were included in the safety and efficacy assessments. Demographic data, general and background characteristics and procedural data were comparable in the two treatment groups. No significant difference in efficacy was observed between the two groups: diagnostic yield was optimal in 90% of the patients in the Iopentol group and in 88% of the patients in the Iopamidol group. Systolic blood pressure 30 min. after the examination showed, in both groups, a slight but statistically significant reduction relative to baseline values (-3.48 mmHg and -3.85 mmHg in the Iopentol and in the Iopamidol group, respectively), while no significant reduction was observed in diastolic blood pressure. A statistically but not clinically significant decrease in heart rate was observed in the Iopamidol group 30 min. after the examination (-5.05%), while this variable remained practically the same in the Iopentol group (-0.58%). No difference was found between the two groups relative to the incidence of discomfort following the injection. Other adverse reactions were experienced by 7 patients in the Iopentol group and by 9 patients in the Iopamidol group: they all promptly recovered after medical treatment, with no sequelae. All but one event in the Iopamidol group (chest and abdominal pain with ECG changes) were mild to moderate and mainly related to the procedure and to the underlying disease. In conclusion, both contrast agents are safe and effective for use in cardioangiography. PMID- 7997611 TI - [Aneurysm of the abdominal aorta. Angiography with magnetic resonance versus color Doppler ultrasonography]. AB - This prospective study was aimed at comparing the diagnostic accuracy of Magnetic Resonance Angiography (MRA) with that of color-Doppler ultrasonography (color Doppler US) in the detection and assessment of abdominal aortic aneurysms. Twenty patients with abdominal aortic aneurysms underwent MRA, color-Doppler US, digital subtraction angiography (DSA) and Computed Tomography (CT) on three consecutive days. Fourteen patients underwent surgical repair of the aneurysm. MRA and color Doppler findings were compared with DSA, surgical and pathologic findings, which were considered as the gold standard. In the 6 patients who refused surgery, CT and DSA were considered the gold standard. MRA always correctly assessed the size and site of the aneurysm, the involvement of the renal and common iliac arteries, the retroarotic course of the left renal vein, the thrombotic component and calcifications. Color-Doppler US always correctly assessed the size and site of the aneurysm, the thrombotic component and calcifications and the involvement of the iliac arteries. In one case color-Doppler US failed to demonstrate the involvement of the renal arteries and the retroaortic course of the left renal vein. Our preliminary results suggest MRA as the best non-invasive technique to study abdominal aortic aneurysms. PMID- 7997612 TI - [Color-Doppler of the renal arteries at their origin. Technical-methodologic problems]. AB - Steno-obstructive diseases of the renal arteries affect mainly the ostium and the proximal vessels. The Doppler US study of the renal arteries can be troublesome on account of their depth, reduced caliber and considerable anatomical variability in their origin, course and number. Recent color-Doppler techniques have helped partially overcome these limitations relative to the identification of both vessels and stenoses. The technique for the visualization of the renal arteries requires supine transverse epigastric, coronal and transcaval scans to obtain a good beam angle. The stenosis can be recognized by the phenomena of turbulence and blood flow acceleration that elicit a typical yellow-green or white color variance, according to the different units. Spectral analysis allows monitoring of spectral broadening, velocity/frequency increase in systolic peak and increase in aortic-renal ratio. Stenoses can be quantified by calculating the stenosis index. The major limitation to the clinical use of color-Doppler US to study steno-obstructive diseases of the renal arteries is the high incidence of supplemental vessels (25-30% of the patients) and early bifurcations of the main branch. Thus, a correct and accurate imaging technique designed to search supplemental vessels plays a major role in decreasing the number of false negatives. Captopril renal scintigraphy is more sensitive than color-Doppler US in the identification of renin-dependent hypertension, but Doppler US is definitely better at detecting stenoses < 60% which may lead to chronic renal insufficiency. PMID- 7997613 TI - [Magnetic resonance angiography at 0.5 Tesla of the renal arteries. Capabilities and limitations of the 2-dimensional phase contrast technique]. AB - To investigate the potentials and limitations of Magnetic Resonance Angiography (MRA) of the renal arteries at mid-field strength, 16 patients with arterial hypertension of suspected renovascular origin were submitted to MRA at 0.5 T with the two-dimensional (2D) phase-contrast technique and to arteriography. MRA yielded diagnostic images in 15 (94%) patients in whom MRA and arteriography identified 38 and 39 renal arteries, respectively. MRA sensitivity and specificity to steno-occlusive alterations of the renal arteries demonstrated by arteriography were 83% and 96%, respectively. These results, although obtained in a small group of patients, indicate that MRA of the renal arteries with a mid field MR system and the 2D phase-contrast technique can allow the diagnosis of steno-occlusive alterations of the renal arteries. Main MRA limitations were its long acquisition time and some variability in the quality of the MRA images. Nevertheless, the ongoing rapid technical developments in the hardware of MR systems leave room for improving the accuracy of mid-field MRA of the renal arteries and justifies optimism as to its role in the screening of renovascular hypertension. PMID- 7997614 TI - [Color-Doppler ultrasonography and hypertension. Functional assessment of the renal region]. AB - Color-Doppler US can be used for the morphofunctional assessment of most arterial districts. In hypertension, color-Doppler US can be used to study the renal arteries for both the diagnosis of renovascular hypertension and better physiopathologic assessment of renal arterial blood flow in essential hypertension. To this purpose, we studied renal flow characteristics with the resistive index in both basal conditions and after pharmacologic stimulation with angiotensin-converting enzyme inhibitors. The resistive index was seen to rise in parallel with hypertension severity, as measured by mean arterial pressure; the change was statistically significant (p < 0.05). Values rose step by step from 57.4 (+/- 4.96) in the right renal artery and from 56.6 (+/- 4.18) in the left one in controls, up to 62.2 (+/- 6.6) in the right and 62.3 (+/- 7) in the left renal arteries of severe hypertensives. After pharmacologic stimulation in controls and in mild hypertensives, resistive index values rose significantly (+2.32 +/- 2.1 and +3.5 +/- 5.2, respectively), while in more advanced stages of the disease this index remained unvaried from a statistical point of view (+0.5 +/- 1.7 in moderate and -0.2 +/- 2.1 in severe hypertensives). These data can be explained by reduced capability of renal blood flow autoregulation, as a consequence of a defined vascular damage. In the follow-up of more severe stages of the disease, although pharmacologic treatment had been optimized and mean arterial pressure values reduced (109.08 vs. 118.25 mmHg), even after a prolonged therapeutic wash-out, an abnormal RI response persisted in controls (-1.79 +/- 2.62 vs. -0.94 +/- 1.64), due to persistent arteriolar damage. To date, it is still to be defined if our studies can be applied not only to populations but also to single patients. PMID- 7997616 TI - [Staging of hepatocellular carcinoma. Comparison of ultrasonography, computerized tomography, magnetic resonance, digital angiography, and computerized tomography with lipiodol]. AB - Accurate staging is necessary in hepatocellular carcinoma (HCC) patients to choose the most appropriate therapeutic approach. In the present study, 50 patients with one or more HCC lesions were prospectively examined with ultrasonography (US), Computed Tomography (CT), Magnetic Resonance Imaging (MRI), digital subtraction angiography (DSA) and CT after intraarterial injection of Lipiodol (Lipiodol CT). The study was aimed at suggesting the most appropriate diagnostic work-up for HCC staging. A hundred and twenty-one HCC lesions were detected in the 50 examined patients by means of the above imaging techniques: namely, 21 patients had single lesions, 15 had two lesions, 4 had three lesions and 10 patients had more than three lesions (range: 4-12). US detected 98/121 lesions (81%), CT 92/121 (76%), MRI 90/121 (74%), DSA 102/121 (84%) and Lipiodol CT 115/121 lesions (95%). The sensitivity of Lipiodol CT was significantly higher than that of all the other imaging techniques (p < 0.05). The detection rate of each technique was correlated with the size of the tumors, which were divided into three groups: lesions < or = 1 cm (no. 28), lesions ranging 1.1 to 3 cm (no. 43) and lesions > 3 cm (no. 50). In the lesions < or = 1 cm, detection rates ranged 29-93%; in this group a statistically significant difference (p < 0.01) was observed between Lipiodol CT and all the other imaging modalities. In the lesions 1.1-3 cm, detection rates ranged 77-93%; in this group a statistically significant difference (p < 0.05) was observed between Lipiodol CT and MRI. In the lesions > 3 cm, sensitivity was very high for all imaging modalities--i.e., 94% or higher; in this group no statistically significant difference was observed among the various imaging modalities. Combined US and CT detected 104/121 lesions (86%), US and MRI 101/121 (83%) and CT and MRI 98/121 (81%). The combination of US, CT and MRI allowed the detection of 107/121 lesions (88%), which markedly improved the results of US alone (the statistical index was just above the one usually considered to be significant). In conclusion, our data suggest the following staging work-up for HCC: (a) US as the first step diagnostic tool; (b) CT and possibly MRI, in the cases with a single lesion at US and in the patients eligible for surgery; (c) Lipiodol CT in the cases which CT and MRI confirmed to be single lesions. PMID- 7997615 TI - [Neonatal hemoperitoneum: role of ultrasonography. Experience with 4 cases]. AB - This study was aimed at investigating the role of US in the newborn with a clinical suspicion of hemoperitoneum. Hemoperitoneum is a dramatic clinical event which may be caused by some obstetrical and fetal factors--breech or complicated delivery, hepatomegaly, macrosomy, anoxic liver congestion being the most frequent causes. Direct or indirect trauma of an abdominal organ during delivery represents the major pathogenetic factor. Clinical symptoms are correlated with the appearance of shock whose intensity is proportional to trauma severity: symptoms may appear even 48 hours after delivery. The authors report their experience with 4 consecutive cases of neonatal hemoperitoneum which underwent US of the abdomen 24 to 72 hours after birth. In the first 3 newborns, US was performed on the basis of a clinical picture of bleeding shock, while in the extant newborn US was performed after a sudden increase in blood transaminase level associated with an obstetrical paralysis of the left arm. The US examinations were performed using a 7.5-MHz sectorial probe unit (Siemens). In all patients, US demonstrated the presence of a liquid effusion in the abdomen which could be referred to hemoperitoneum. In two patients, it was associated with a traumatic focal alteration of the liver parenchyma, in the third with a diffuse subcapsular liver hematoma and, finally in the fourth patient with a disconnected splenic vascular pedicle which was at surgery demonstrated. In conclusion, US is indicated as the most reliable and valuable diagnostic technique in the study of neonatal hemoperitoneum. The authors believe abdominal US to be essential in all the neonatal cases where hemoperitoneum is suspected and in selected cases presenting specific risk factors, to allow a rapid diagnosis and better treatment planning. PMID- 7997617 TI - [Ultrasonography and retrograde transpapillary cholangiopancreatography combined with sphincterotomy in the diagnosis of choledochal lithiasis. Our experience with 87 patients]. AB - We retrospectively reviewed the US findings of 87 patients to assess US sensitivity in the detection of choledochal (CBD) stones. Endoscopic retrograde cholangiopancreatography (ERCP) with endoscopic sphincterotomy (ES) was used as the diagnostic standard, except for 1 patient who underwent surgical exploration. First, the distal CBD was studied with transverse and parasagittal US scans through the head and uncinate portions of the pancreas. CBD stones usually appeared as hyperechoic lesions, most of them with acoustic shadowing. In some cases, the stone moves during real-time scanning, which further confirms the diagnosis. Fifty-four of 87 patients had CBD stones and US detected them in 46 cases. The absence of a stone was diagnosed correctly in 28 of 33 patients. In our series, US sensitivity, specificity and accuracy were 85%, positive predictive value 88% and negative predictive value 78%. If the distal duct cannot be demonstrated adequately or if duct size is normal, US sensitivity in detecting stones decreases and other examinations, such as ERCP, should be performed. We conclude that US can be used as the diagnostic method of choice to examine the patients with suspected biliary tract disease. Although ERCP is the gold standard for diagnosis and therapeutic purposes in choledochal stones, it remains an invasive technique and must therefore be held in reserve. PMID- 7997618 TI - [Carcinoma of the uterine cervical canal. Staging and biometric assessment with magnetic resonance]. AB - In uterine cervical canal carcinoma, the current clinical FIGO criteria often fail not only to differentiate stage IA2 from stage IB but also to demonstrate possible parametrial involvement. Moreover, the analysis of tumor volume and of the depth of neoplastic stromal invasion is not very reliable. The authors investigated MR accuracy in the definition of such variables: to this purpose, 24 patients with histologically confirmed endocervical adenocarcinoma were submitted to MRI, which was performed with an 0.5-T superconductive magnet. Sagittal and oblique transverse or sometimes coronal SE images, oriented so as to be perpendicular to longitudinal cervical major axis were obtained with T2 weighting (TR 1800 ms, TE 25-90 ms). MR data were correlated with pathologic findings. MR accuracy in demonstrating parametrial involvement was 92%, its sensitivity was 86% and specificity 97%. Volumetric MR data showed a high correlation (r = 0.970) with those derived from pathologic findings. In 92% of cases stromal invasion exceeded 5 mm. MRI, thanks to its high accuracy, should be included in diagnostic pretreatment protocols, even though FIGO criteria do not require it yet, especially in the presence of an endocervical adenocarcinoma. Moreover, the accurate definition of tumor volume can allow less extensive surgery with the same survival rates and fewer complications, which are frequently observed after radical hysterectomy. PMID- 7997619 TI - [Anatomic characteristics of pelvic fascia and ligaments in computerized tomography]. AB - The pelvic fascia consists of two layers, the parietal and the visceral layers I whose appendages represented by various septa and ligaments subdivide the pelvis in intra- and extraperitoneal spaces. These structures are extremely thin but can be demonstrated thanks to the high-quality images obtained with the latest CT scanners and to the good natural contrast of pelvic fat. To assess the visibility of the anatomic features of these structures, 50 patients with no pelvic conditions which could affect the thickness of the pelvic fasciae and ligaments were examined with CT. The pelvic visceral fascia was clearly demonstrated in 60% of cases, the rectovesical and rectovaginal septa and the medial umbilical ligaments were demonstrated in 100% and 92% of cases, respectively. The umbilico prevesical fascia and the lateral umbilical ligaments were poorly demonstrated. The depiction of these structures improves the knowledge of pelvic anatomy and yields major pieces of information to better understand several pelvic conditions. PMID- 7997620 TI - [Pelvic fascia, ligaments, and spaces in neoplastic disease in computerized tomography]. AB - The fasciae and ligaments which are visible on CT images as extremely thin structures in normal conditions tend to appear thicker in such abnormal conditions as pelvic neoplasms and are therefore easily demonstrated on axial scans. To assess the CT patterns and the meaning of fascial thickening, the CT images of 40 patients with pelvic tumors (25 rectal, 7 uterine, 6 ovarian and 2 bladder lesions) were examined. Ten cases of peritoneal carcinomatosis with ascitis were also studied. The umbilico-prevesical fascia was demonstrated in 60% of cases, while the medial umbilical ligaments, the pelvic visceral fascia and the rectovesical and rectovaginal septa were detected in 90, 96 and 100% of cases, respectively. Fascial thickening is not a specific sign of neoplastic disease since it can be due to neoplastic infiltration or be the response to an irritative stimulus. Moreover, fascial thickening can be observed also in inflammatory conditions of the pelvis and following major traumas. Thickened fasciae and ligaments make the demonstration of paravesical, intra- and extraperitoneal spaces easier, which is useful to distinguish both etiology and site of pelvic fluid collections. All these pieces of information lead to better understanding pelvic abnormalities. PMID- 7997621 TI - [Computerized tomography in the differential diagnosis of non-gynecologic abdomino-pelvic masses]. AB - The female pelvis is an anatomical region where masses can be found originating from pelvic organs, mostly from the genital system or else from abdominal organs and systems, by continuity, by contact or by metastatic spread. The clinician needs to define and characterize a pelvic mass since treatment options can vary greatly. If a malignant pelvic lesion is clinically suspected, ultrasonography is the investigation technique of choice, whose differential diagnosis accuracy is good especially in gynecologic conditions. However, in nongynecologic masses, US diagnostic yield is poorer, which led us to retrospectively review 31 such cases. CT was used to assess the mass origin and tissue characterization to define the clinical role of this method. On the whole, CT yielded good results (80.6% overall diagnostic accuracy, 25/31 cases) which however differed according to the different pathologic conditions. Gastrointestinal system conditions, tumors and inflammations were easy to diagnose with CT (11/15 cases, 73.3%), except for the patients with intestinal cancer spreading to the ovaries, that is, a Krukenberg's lesion, or the cases with an abscess hiding the annexa and thus preventing CT from detecting the mass origin, be it intestinal or annexial. CT diagnostic accuracy was high in extraperitoneal (retro- and properitoneal) masses (8/8 cases, 100%), but much lower (75%, 6/8 cases) in the diagnosis of primary intraperitoneal organs conditions. To conclude, CT is confirmed as an accurate imaging technique in the differential diagnosis of nongynecologic abdominopelvic masses. The mass origin is usually correctly detected and tissue characterization is accurate, which provides the clinician with enough pieces of information for best treatment planning. PMID- 7997622 TI - [Homogenized thoracic radiography]. AB - The major obstacle to optimal radiographic depiction of the chest has always been its anatomical features and, in particular, the considerable difference in X-ray beam attenuation between pulmonary and mediastinal structures. At least 40% of this region cannot be visualized in an optimal way. Therefore, much technological work was done to overcome this limitation, which has recently led to the development of electronic (Amber) and mechanical (homogenization) filtration systems. This study was aimed at assessing the capabilities of mechanical filtration, in terms of anatomical representation and lower biologic cost, the latter intended as lower exposure and absorbed doses. Therefore, eight radiologists studied 40 negative radiographs, i.e., a homogenized radiograph and a non-homogenized one per patient, twenty patients in all. The statistical analysis of the radiographs demonstrated the homogenized technique to allow better visualization of all the anatomical structures examined, i.e., trachea, carina, right and left main bronchi, aorta, spine and retrocardiac region. In contrast, the two radiographic techniques yielded much the same results in the depiction of the pulmonary pattern. As for dosimetry, good results were also obtained, because the homogenizer made it possible to reduce both exposure and absorbed doses to the lung and thyroid, while in the mediastinal region the absorbed dose remained similar to that measured with the non-homogenized even though exposure dose was increased mildly. PMID- 7997623 TI - [Orbital metastasis of breast carcinoma. Radiologic picture]. PMID- 7997624 TI - [A rare case of metastasis of choroidal melanoma in male breast. Mammographic and ultrasonographic diagnosis]. PMID- 7997625 TI - [Computerized tomography of pleural lipoma. Report of 3 cases]. PMID- 7997626 TI - [Computerized tomography and ultrasonography characteristics of spleen involvement in Wegener's granulomatosis. Description of a case]. PMID- 7997628 TI - [Magnetic resonance in the pre- and postoperative study of a case of multiple adenomas of the liver]. PMID- 7997627 TI - [Hepato-spleno-renal mycotic microabscesses in immunocompromised patients. Our experience]. PMID- 7997629 TI - [Atypical hepatic cavernous angioma. Angiographic demonstration of portal blood supply]. PMID- 7997631 TI - [Transduodenal drainage in pancreatic pseudocysts. Role of computerized tomography and treatment planning]. PMID- 7997630 TI - [Multiple hepato-splenic abscesses in children. Ultrasonography and computerized tomography characteristics]. PMID- 7997632 TI - [2 rare cases of renal pseudotumors: infarction and hemangioma]. PMID- 7997634 TI - [Congenital mullerian prostatic cyst: percutaneous treatment]. PMID- 7997633 TI - [Hematometracolpos in congenital utero-vaginal malformation. Description of a case studied with ultrasonography and magnetic resonance]. PMID- 7997635 TI - Interrater reliability of the Motivation Assessment Scale: failure to replicate with aggressive behavior. AB - The Motivation Assessment Scale (MAS) was used to identify the variables maintaining aggressive behaviors exhibited by 18 adolescents and adults with severe to profound intellectual disability. Each client was rated by two staff members. A variety of measures were calculated to assess interrater reliability. Pearson coefficients across the 18 pairs of raters ranged from -.667 to .722 with an overall correlation of .034. Five of the 12 positive correlations were significant at the .05 level. Correlations across each of the 16 questions of the MAS ranged from -.337 to .425. None of these correlations were significant. Similarly low reliability was obtained when percentage of agreement measures were calculated, although 8 of the 18 pairs of raters (44.44%) did agree on the source of reinforcement maintaining the client's aggressive behavior. These results suggest that for some individuals the MAS may not represent a viable alternative to more formal functional analysis procedures. PMID- 7997636 TI - Training parents to observe and record: a data-based outcome evaluation of a pilot curriculum. AB - Despite the prevalence of training parents in the use of child behavior management strategies, relatively little investigative attention has been devoted to promoting acquisition of parent observational and recording skills. In this study, we examined the efficacy of a brief curriculum designed to teach parents how to observe and record targeted child behaviors systematically. Subsequent to instruction, each of six participating parents demonstrated, in an analogue context, higher levels of both occurrence and nonoccurrence agreement, based upon their recordings of child behavior, when compared with those of a panel of experienced professionals. Agreement of parental recordings with those of professionals typically increased to a predetermined mastery criterion and stabilized subsequent to training, relative to a high degree of variability during baseline. Results are discussed in terms of directions for further refinement of the curriculum and additional study of its impact. PMID- 7997637 TI - Development of the psychopathology instrument for Mentally Retarded Adults Sexuality Scale (PIMRA-S). AB - Little research or attention has been focused on identifying sexual problems or difficulties that people with mental retardation commonly experience. Scale development represents an important area for study to help identify these problems and to evaluate treatment outcome. To address this need, the Psychopathology Instrument for Mentally Retarded Adults-Sexuality Scale (PIMRA-S) was designed to assess psychosexual disorders in mild and moderate mentally retarded persons. Eighty-six mild and moderately mentally retarded adults, ages 20 to 60, were studied using the PIMRA-S. Scale development of this type was considered important because little has been done to assess sexual problems among mentally retarded persons. Fifty-eight items were developed based on evaluations of the research literature and interviews of experienced professionals. A preliminary assessment of reliability was conducted. The psychometric characteristics of these preliminary analyses were favorable. In addition, information was reported on the rate of sexually aberrant behavior exhibited by people identified with mild and moderate mental retardation. Differences in the rate of sexually aberrant behavior were addressed as a function of living and work placement, positive history of sexual abuse, need for treatment of sexual problems, and psychiatric diagnosis. Implications of these results for further scale development are discussed. PMID- 7997638 TI - Specialized group homes for persons with severe or profound mental retardation and serious problem behaviour in England. AB - Thirteen people with severe or profound mental retardation identified by their local service agencies as presenting the most serious problem behaviour were transferred from institutional care to specialized group homes. A multiple time series design and direct observation were used to evaluate whether there was any change in their level of participation in meaningful activity; social interaction and problem behaviour were also observed. Participation increased significantly on transfer and included a wider range of activities. The majority of participants did not increase their major problem behaviour. The results support the view that individualised community-based placements can replace institutions for this group of clients. PMID- 7997639 TI - Training quality job interviews with adults with developmental disabilities. AB - Supported work models of vocational integration have increased the employability of individuals with developmental disabilities. Interview questions most frequently used and corresponding responses considered most beneficial to job applicants were derived from an empirical analysis of the "hiring community" and served as a basis for the development of the verbal job interview skills training package evaluated in this research. Dependent measures were objective, behavioral indices of the quality of job interview responses. One-to-one training by a direct training staff, job coach, and a trained behavior analyst resulted in improved responding by all subjects as indicated in a multiple baseline design across interview questions. Improved quality in responding to questions generalized to variations in interview questions, to a novel interviewer, and in an in vivo interview situation. Finally, global measures of social validity support the value of the quality-of-response training. PMID- 7997640 TI - Fever and the control of gram-negative bacteria. AB - Although it seems obvious that fever has some important general adaptive value, it is still not clear by what means this function is manifested. One postulate is that febrile conditions result in the sequestration of soluble iron, effectively starving some pathogens of that essential nutrient. On the basis of our recent experiments, we propose a new mechanism for how fever serves to restrict a wide range of Gram-negative bacteria. The elevated temperature prevents the bacteria from synthesizing their protective LPS, thereby enabling serum complement to perforate and kill the invading pathogens even prior to the production of host antibodies. PMID- 7997641 TI - Phylogenetic relationships among bacteriorhodopsins. AB - Retinal-containing proteins of archaea comprise a single family of homologous proteins that fall into three clusters correlating with function: the proton transporting bacteriorhodopsins, the chloride-transporting halorhodopsins and the colour-discriminating sensory rhodopsins. Statistical and phylogenetic analyses, a multiple alignment and average hydropathy and similarity plots of these protein sequences are presented. Available evidence suggests that sequence conservation generally correlates with functional significance. Little or no evidence substantiates the proposal that these proteins arose by a tandem intragenic duplication event. The bacterial rhodopsin family appears to have evolved from a common ancestor without recognizable intragenic rearrangements. PMID- 7997642 TI - Secretion of a temporally controlled cell-associated protein in Arthrobacter aureus: production of the protein and inactivation of its structural gene. AB - Arthrobacter aureus secretes 2 proteins of 22 and 100 kDa (P22 and P100, respectively). P22 is a protease, while P100, of unknown function, is associated with the cells before being released into the medium. An immunologically related P100 protein was also found in the culture supernatant of A. ureafasciens. Despite the fact that production of P22 and P100 proteins is induced by growth in the presence of bovine serum albumin, their synthesis is not always induced coordinately. Inactivation of the P100 chromosomal structural gene had no effect on growth characteristics of the mutant under inducing conditions. PMID- 7997643 TI - Properties of Yersinia enterocolitica porins: interference with biological functions of phagocytes, nitric oxide production and selective cytokine release. AB - We have extracted and purified Yersinia enterocolitica ATCC 9610 porins that have molecular weights of 36-38 kDa. They inhibited phagocytosis and phagosome lysosome fusion (30%) in human monocytes and caused enhanced nitrite production. Preincubation of polymorphonuclear neutrophils with porins (1-10 micrograms/ml/10(6) cells) induced a reduction in chemotaxis, adherence to nylon wool and chemiluminescence. Human lymphomonocytes treated with Y. enterocolitica porins showed a distinctive cytokine profile. Interleukin-1 alpha, interleukin-6 and tumour necrosis factor alpha were released within 3-6 h, while interleukin-8, gamma interferon and granulocyte-macrophage colony stimulating factor were released after 18 h. Interleukin-3 and interleukin-4 were not detected at up to 48 h of incubation. In conclusion, these immunomodulating and histotropic properties may account for Y. enterocolitica infection and its sequelae. PMID- 7997644 TI - Ufr/s variation in Escherichia coli K12: a reversible double-mutation or alternate chromosome expression in non-complementing diploids? AB - A novel form of bacterial variation found in an FhuA- mutant of Escherichia coli K12 was characterized by the alternation of (1) simultaneous resistance to lipopolysaccharide-specific phage U3 and to FhuA-specific agents (Ufr phenotype); and (2) a return to the sensitivity pattern of the initial strain (Ufs). In Ufr cells, loss of the U3 receptor permitted C21 adsorption without modifying the sensitivity to other tested phages or colicins. Genetic analysis revealed that Ufr variants were altered at two distinct loci. Ufr bacteria, though derived from a strain F- devoid of classical gene transfer mechanisms, were transiently able to promote mating between themselves and, to some extent, with other bacteria, including Rec-. Heterogenic matings resulted in the formation of persistent heterozygotes segregating Ufr- and Ufs-like bacteria. Pedigree analysis and subcloning of heterozygotic isolates indicate that they were diploids, as was the initial Ufr strain. Functional genetic complementation between these two genomes was only transient and the alternative forms were likely to result from the expression of a single chromosome of the heterozygotes. Mutation occurred in either form without causing any change in the alternative form. PMID- 7997645 TI - Evidence for the involvement of different genospecies of Borrelia in the clinical outcome of Lyme disease in Belgium. AB - In addition ot Borrelia burgdorferi, recognized as the aetiological agent of Lyme disease, at least two separate genospecies have recently been described. A relationship between infection by strains belonging to different genospecies and clinical outcome has been suspected. In this paper, 9 cases of Lyme arthritis were attributed to infection by B. burgdorferi sensu stricto, 18 cases of neuroborreliosis to B. garinii and one case of acrodermatitis chronica atrophicans to a strain of B. afzelii. These conclusions were based on the preferential reactivity of sera with antigens of given strains in Western blots and on residual reactivity after absorption of sera with antigens of representative strains. No conclusion could be reached concerning sera of 10 patients with erythema migrans. PMID- 7997646 TI - Easy-to-perform modified Elek test to identify Shiga-like toxin-producing diarrhoeogenic Escherichia coli. AB - We determined whether Shiga-like toxin I (SLT-I) -producing diarrhoeogenic Escherichia coli could be detected by a modified Elek tests. The test (SLT Elek test) is based on the principle of the Elek test and the Ouchterlony double-gel diffusion. The development of the SLT Elek test was preceded by a preliminary study; the purpose of the later was to establish whether a simplified purification procedure of SLT-I (involving bacterial sonic extract, "Affi-Gel Blue" chromatography and anion- and cation-exchange liquid chromatography) could be employed in the preparation of rabbit antisera to SLT-I. SLT-I-specific antisera were obtained after adsorption of sera with bacterial sonic extract from non-toxigenic E. coli. A total of 135 strains of E. colo were tested by the SLT Elek test (100 SLT-I-negative and 35 SLT-I-positive). The results of the SLT Elek test and the Vero cell test correlated well: 30 strains gave positive results and 100 strains gave negative results in both tests. Only 5 strains gave discrepant results: they were weakly positive in the Vero cell assay, whereas 3 gave borderline reactions and 2 were negative in the SLT Elek test. Positive predictive value was 1, negative predictive value was 0.98; the SLT Elek test was 91% sensitive and 100% specific. PMID- 7997647 TI - Alterations in renal function in experimental congestive heart failure. AB - The delicate interplay between vasoconstrictors and vasodilators preserves glomerular filtration in CHF despite marked hypoperfusion. Activation of vasoconstrictive systems seems to depend on the severity and the chronicity of the disease. The importance of renin-angiotensin, sympathetic nerves, vasopressin and counterregulatory ANP, and prostaglandins in CHF has been elucidated. Possible roles of newly identified substances, such as endothelin and EDRF, deserve investigation. PMID- 7997648 TI - Effects of neural and humoral agents on the renal tubules in congestive heart failure. PMID- 7997649 TI - Hemodynamic and hormonal alterations in patients with heart failure: toward a contemporary definition of heart failure. PMID- 7997650 TI - The renal-cardiac connection: renal parenchymal alterations in patients with heart disease. PMID- 7997651 TI - Vasodilators and inotropic agents in the treatment of congestive heart failure. AB - The treatment of patients with congestive heart failure is predicated on an underlying knowledge of the pathophysiology of the syndrome. To date, the most effective therapy has been a combination of diuretics and ACE inhibitors. However, there are specific situations where direct-acting vasodilator therapy is helpful as adjunctive or replacement treatment. As of this writing, digitalis remains the sole orally active positive inotropic drug approved by the FDA for the treatment of patients with heart failure. Although the development of orally active positive inotropic drugs has been generally disappointing, research continues in this area. On the surface, progress in development of vasodilators and inotropic agents for heart failure has been successful, but the average improved survival time is only about 9 to 18 months. Given the current scope of the problem of heart failure, development of newer vasodilators and inotropic therapy as well as agents designed specifically to inhibit the neuroendocrine activation in the syndrome of heart failure can be expected. PMID- 7997652 TI - The use of diuretics in congestive heart failure. AB - Diuretic resistance in patients with congesting heart failure is for the most part due to pharmacodynamic factors related to increased reabsorption of solute at other parts of the nephron. This mechanism explains the rationale for using combinations of diuretic agents affecting solute reabsorption at different nephron sites in such patients in contrast to a strategy of escalation of loop diuretic doses. Understanding the mechanisms by which diuretic resistance occurs in patients with CHF has allowed design of appropriate dosing regimens of these drugs and rational use of combinations of diuretics. PMID- 7997653 TI - Fluid and electrolyte disorders in congestive heart failure. PMID- 7997654 TI - [The clinical and legal criteria concerning the corroboration of the factors involved in cataract treatment]. PMID- 7997655 TI - [Mitral valve prolapse. III. The methods for diagnosis and evaluation]. PMID- 7997656 TI - [Suicidal behavior: medicolegal epistemology (2)]. PMID- 7997657 TI - [Parasitic hypereosinophilia]. PMID- 7997658 TI - [Current data on the pathogenesis of atherosclerosis (I)]. PMID- 7997659 TI - [The treatment of arterial hypertension in the middle-aged and elderly]. PMID- 7997660 TI - [The manifestations of biorhythms in behavioral activity. I]. PMID- 7997661 TI - [Thyroid actinomycosis (actinobacteriosis)]. AB - An extremely rare case (the 15th case reported in the literature, according to our knowledge) of the infection with Actinomyces Israeli localized at the level of thyroid gland is presented. Although the clinical and imaging data, the fine needle aspiration biopsy, and the intraoperative aspect clearly suggested the diagnosis of thyroid cancer, the microscopic examination surprisingly identified "sulfur granules", specific to actinomycosis, so that treatment and prognosis were reconsidered. PMID- 7997663 TI - [The surgical treatment of tarsometatarsal dislocations]. AB - Based on their own experience and literature, the authors review the etiopathogenic, anatomo-clinical, diagnostic and management aspects of torso metatarsal dislocations. The surgical treatment by open reduction or reposition arthrodesis, as a first or secondary step, using Kirschner wire and staples, are more and more used. The early and late complications, which may aggravate the long-term functional prognosis are detailed. PMID- 7997662 TI - Lumbar spinal stenosis by postdiscectomy hyperostosis. AB - The mesenchymal repair process of the connective tissue in the surgical wound following lumbar laminectomy presents three aspects: postoperative epidural scar, heterotopic bone formation in the epidural scar and vertebral hyperostosis around laminectomy. Twelve cases of lumbar spine hyperostosis consecutive to laminectomy, confirmed by x-ray findings and surgery are presented. The main symptom at presentation was a recurrent sciatic neuritis. Lumbo-sacral spine films showed a "bright" focal condensation in the previous surgical. Lamina inferior and superior and the articular facets were hypertrophic. Surgery confirmed the hyperostosis and compressive lumbar spine stenosis or foramen stenosis. PMID- 7997664 TI - Breast-feeding and natural family planning. AB - The record of 50 postpartum women who intended to breast-feed for longer than 6 month were analyzed. Fifty percent of the women breast-feed longer than 12 month, and 50% resumed menses by 40 weeks after childbirth. Fifty-two women record of mucus and basal body temperature (BBT) fort at least 4 week before resumption of menses. Ovulation before menses while fully breast-feeding was probable in only one woman. Fifty percent of the first postpartum cycles had a short luteal phase Thirty-five women chose NFP to avoid pregnancy during the study period. Mucus and BBT proved to be a good marker of ovulation during postpartum cycles. Confidence in NFP during lactational amenorrhoea and first postpartum cycles in analyzed. Finally, research aimed at improving the teaching and use of NP for postpartum breast-feeding women is described. PMID- 7997665 TI - [The presence in pregnant women of the risk factor of serum antibodies against 9 viruses with significance in materno-infantile pathology and the transfer of these antibodies to the newborns]. AB - Indirect enzyme immunoassay, performed with Labsystems (Helsinki) kits, in 30 mothers and their newborns, revealed that 100% of parturient women present IgG antibody to hepatitis A (HAV), herpes simplex 1, and measles viruses, constantly transferring these antibodies to their newborns. 78.6% of the women had IgG to rubella (German measles) virus, passively transmitting them to their offsprings. Serological markers (HBsAg and anti-HBc) of hepatitis B virus infection were present in 42% of the investigated women, anti-HBc being also present in the serum of the newborns. Between the identified risk factors (in the past obstetrical history, current pregnancy, labor and early postnatal period) and the spectrum of IgG antibodies present in mothers no significant correlations were revealed. The same obvious lack of correlation between IgG antibodies and risk factors in the neonate (prematurity, low birth weight, malformations) was also found. However, the presence of IgG anti-measles (2 case), IgM anti-rubella (1 case) and IgM and HAV (4 cases) was associated, in the same order, with interstitial pneumonia, hepatosplenomegaly and death, icterus neonatorum, cardiovascular and neurologic malformations. Neither mothers nor their offsprings presented anti-HIV antibodies, suggesting that in the investigated patients no perinatal transmission had occurred. PMID- 7997666 TI - [Glutathione, a biochemical indicator for different types of cellular oxidative stress. II. Ethanol poisoning]. AB - Eight male volunteers, all alcohol addicts selected from the patients of the Padureni unit, deprived for a minimum of two weeks of alcohol, but with an at least 2-year history of alcohol addiction, received 0.5 ml absolute alcohol/kg body weight. Following dynamically the alteration of plasma reduced glutathione content, a significant increase (+8.27%) 30 minutes after alcohol ingestion and a decrease (-7.02%) before ingestion, as compared to plasma glutathione level in sex and age-matched clinically normal subject (100%) was noticed. The change in the --SH groups content in plasma after chronic alcohol ingestion leads to the occurrence of cell oxidative stress, as well as to a decreased resistance of hepatic cell and whole body as a result of the lipid peroxidation process and/or occurrence of detrimental reactive radical species, issuing from O2. PMID- 7997667 TI - [The clinicopsychological and therapeutic significance in the depression-pain relationship]. AB - The frequency of depression-pain association, gives the authors the opportunity of evaluating the actual pattern of managing pain according to its sensory discriminatory, affective-emotional, cognitive and behavioral features. The neurophysiologic, affective and psychologic factors generally correlate in the induction and evolution of pain, being dependent on the individual reactivity environmental and socio-cultural relations. The efficacy of antidepressive drugs in the therapy of pain, explained by their action on the serotoninergic systems, advocates the clinical relationship depression-pain, but also their analgesic properties independent from the thymoanaleptic effect. The results of the clinical essays the authors have carried on some antidepressants (Imipramine, Amitryptyline, Mianserine, Maprotyline) evidenced their effect on the various forms of manifestation and localizations of pain complains. The amelioration of pain, certified by the use in dynamics of Hamilton's depression scale, occurs earlier than the improvement of depressive symptoms, thus attesting the analgesic properties of the antidepressants. The preservation and merging of these effects during the investigation interval, at the same time with an improvement in the depressive symptoms support the clinical correlation depression-pain, emphasizing the complex character of the algopathic syndrome, both somatically and mentally. PMID- 7997668 TI - The timing of violence amongst psychiatric in-patients. AB - The timing of violence among psychiatric in-patients with reference to the time of day, day, month and season over a four-year period were studied. Most of the violence occurred in the daytime. There was no daily variation, but there were spring and summer peaks of violence. The implications of these findings on staffing are discussed. PMID- 7997669 TI - [Phylogenetic aspects of the respiratory apparatus of vertebrates compared with human ontogeny]. PMID- 7997671 TI - [Benzimidazole derivatives with antihypertensive and platelet antiaggregant actions]. AB - The changing of the chemical structure of 2-benzylbenzimidazole, the active substance of Dibazol (Tromesedan), generated five analogous structures. Two salts of the same active substance have been synthesized in view of improving some of the pharmacological and toxicological features. The results of the anti-AHT and platelet aggregation actions are also presented. PMID- 7997670 TI - [The management of acute complications in gastric cancer]. AB - Forty-five acute complications (perforations and upper digestive hemorrhages) occurring in 650 admitted and operated gastric cancer patients were investigated. Despite all problems raised by these complication (gastric cancer, most commonly in advanced stages and invading the neighboring areas, the poor general condition of the patients, age-related deficiencies), the authors regard the removal of the complicated tumor and sometimes wide gastrectomy (the concomitant resection of gallbladder, spleen, atypical liver resection transverse colon resection) as the only solution for the complications, the postoperative complications and early recurrences of the complications as well as mortality rate being at the same time reduced. PMID- 7997672 TI - Syntheses of anticancerous substances. Syntheses and study of the toxicity of some di-(beta chloroethyl)-amides with N-(O-nitrobenzoyl)-amino acid supports. PMID- 7997673 TI - [Experimental research on the toxicity of the product orthochlorobenzene sulfur chloride]. AB - The potential of toxic action in rats of orthochlorbenzol sulphochloride, administered intragastrically in single doses and in daily doses included in food, was estimated. Other bioenzymatic parameters of liver function (transaminase, gammaglutamyltransferase, glutamatdehydrogenase etc.), which presented changes in all experiments performed during this investigations, were also analyzed. Based on the obtained results, stop-gap suggestions of maximum admitted concentrations in environmental elements and air at the work places (0.5 mg/cubic meter) were made. PMID- 7997674 TI - [Peroxide radicals in the metabolism of toxic substances]. AB - The free radicals resulting from the metabolism of oxygen and some xenobiotics, can induce, when a limit concentration is exceeded, toxic effects due to their action on DNA, enzymes and fatty acids. Therefore, the association of oxygen therapy with drug administration may have a more or less beneficial effect. Thus, in a long-term treatment with drugs which by metabolized release free radicals, the use of exogenous compounds for protecting the human body need to be administered. PMID- 7997675 TI - [The difficult diagnosis]. PMID- 7997676 TI - [Anatomicoclinical challenges in acute dissection of the aorta]. PMID- 7997677 TI - [A bimalleolar fracture associated with an astragalotibial dislocation in children]. PMID- 7997678 TI - [The treatment of Meniere's disease with captopril (a clinical case)]. PMID- 7997679 TI - Epidemiology and natural history of gastro-esophageal reflux. PMID- 7997681 TI - [The usefulness of the anthropobiometry method in paternity studies]. PMID- 7997680 TI - [An anatomicosurgical study of the extrahepatic bile ducts]. PMID- 7997682 TI - [The modern implications of ecoepidemiology]. PMID- 7997683 TI - [The interrelations between anodontia and the expression of digitopalmar dermatoglyphics]. PMID- 7997684 TI - [Pharmacotoxicological studies of a natural plant product in the PT series. I. The chronic toxicity of the product PT 2A]. PMID- 7997685 TI - [The characteristics of the psychological factor in anodontia]. PMID- 7997686 TI - [Transthoracic aspiration fine-needle biopsy. Its limits and potentials]. PMID- 7997687 TI - [The study of liposomes--rapid methods]. PMID- 7997688 TI - Bioethics education--strategy and methods. PMID- 7997689 TI - [Medical ethics in the publishing and activities of the Society of Physicians and Naturalists in Iasi (on the 160th anniversary of the existence of the society)]. PMID- 7997690 TI - Research on unconventional medicine. PMID- 7997691 TI - Risk factors for cardiovascular disease--a comparison between Swedes and immigrants. AB - OBJECTIVE: To explore and compare risk factors for cardiovascular disease in Swedes and immigrants. DESIGN: Descriptive analysis of data obtained by personal interview, laboratory investigations, and clinical examination by a trained nurse. SETTING: Varby Health Centre, located in a suburb of Stockholm. The health centre has 32 percent immigrants in its catchment area. SUBJECTS: 2238 participants aged 25-54 years who attended for a health check in 1989-90. MAIN OUTCOME MEASURES: Ethnicity, age, sex, smoking habits, body mass index(BMI), serum-cholesterol, blood glucose, and blood pressure. RESULTS: 30 different nationalities participated and were classified as Swedish, Finnish, Mediterranean and "Other". Mediterraneans had a higher BMI in spite of the fact that their blood pressures were significantly lower. The Finns had the highest mean cholesterol values. Smoking rates among Mediterranean men were high (58%). 40% of the Swedish men smoked. Only 14% of the Mediterranean women aged 45-54 years smoked. The smoking rates increased in age groups 35-44 years (29%) and 25-34 years (46%). CONCLUSIONS: We found important ethnic differences in risk factor patterns. On the basis of our findings, Finnish immigrants should fare the worst. Special efforts should be directed at Finns, focusing on diagnosis and treatment of hypertension and hypercholesterolemia, and at Mediterraneans on overweight and smoking. PMID- 7997693 TI - Management of depression in elderly general practice patients. AB - OBJECTIVE: To describe general practitioners' (GP) management (i.e., recognition and treatment) of depression in elderly patients. DESIGN: Two separate studies were performed: (a) to study recognition of depression, a postal survey was sent to GPs; (b) to evaluate the consistency of treatment, patients considered depressed by GPs were described. SETTING: general practices in the West of The Netherlands. SUBJECTS: 65 GPs, and 44 patients of 7 GPs. MAIN OUTCOME MEASURES: (a) degree of recognition of depression as described in major depression case vignettes (b) consistency of treatment. RESULTS: (a) On average 65% of the GPs recognized every depressive symptom in case-vignette one, while 52% of GPs recognized each symptom in case two. Most (39) doctors used a time criterion of less than 5 weeks for depressive disorder. (b) Depressed patients with at least three depressive symptoms all received treatment. Chronically depressed patients appeared to be treated somewhat inadequately. CONCLUSION: The results suggest some inadequate knowledge of criteria for major depression and some inconsistency in treatment. The management of depression in elderly GP patients appears to need improvement. PMID- 7997692 TI - Gender and social patterning of health: the Norsjo cardiovascular preventive programme in northern Sweden 1985-1990. AB - OBJECTIVE: To assess the extent to which the impact of social stratification on cardiovascular disease (CVD) risk factors was different among men and women. DESIGN: Pooled data from six (1985-90) cross-sectional health surveys. SETTING: The intervention area is an inland municipality, Norsjo, in northern Sweden with a population of 5,300 inhabitants. MAIN OUTCOME MEASURES: Smoking, high blood pressure, hypercholesterolaemia, and perceived health status. RESULTS: Almost half of the study population had hypercholesterolaemia (> or = 6.5 mmol/l), 19% of men and 25% of women were smokers, and 30% and 29%, respectively, had hypertension. Age had a strong impact on all outcome measures. Social factors were associated with smoking in women and with hypercholesterolaemia in men. There were no sex differences in perceived good health. The likelihood of self assessed good health decreased with increasing risk factor load, with the exception of hypercholesterolaemia, in all social strata. CONCLUSION: The present study implies the importance of considering age, gender, and social differences in intervention and evaluation of CVD preventive programmes. The study also demonstrate that self-defined health contains important information on cardiovascular risk profile. PMID- 7997694 TI - Urinary incontinence in primary health care. 1. Perceived knowledge and training among various categories of nursing personnel and care units. AB - OBJECTIVES: To investigate perceived knowledge, skills and education of urinary incontinence (UI), focusing on UI facts, product assessment, and quality of care. DESIGN: A quantitative-qualitative questionnaire study. SETTING: Three different care units; a health care centre, a nursing home, and a geriatric clinic in Sweden. SUBJECTS: 254 nurses, nursing assistants, and auxiliary nurses. MAIN OUTCOME MEASURES: Responses to questionnaire. RESULTS: The study shows fragmentary knowledge about UI facts, aid products, and costs, and a lack of holistic view. The differences in knowledge between the groups were small but registered nurses generally showed better results, probably due to their longer vocational training. The health care centre had the best total knowledge as regards facts about UI. CONCLUSION: All categories of nursing personnel wanted more knowledge about UI care and aids, which indicates that improvements in quality of care could be achieved by increasing product awareness. PMID- 7997695 TI - Urinary incontinence in primary health care. 2. Care routines and consequences- perception of various categories of nursing personnel and care units. AB - OBJECTIVE: To find out whether the nursing personnel's perceptions of urine incontinence (UI) care routines and patient observations were in agreement with quality of care, and to analyse differences between nursing personnel categories and care units. DESIGN: A quantitative-qualitative questionnaire study. SETTING: Three different care units; a health care centre, a nursing home, and a geriatric clinic in a county in Sweden. SUBJECTS: 254 nurses, nursing assistants, and auxiliary nurses. MAIN OUTCOME MEASURES: Responses to questionnaire. RESULTS: Faulty perception of UI, diagnosis and treatment possibilities. Care routines about hygiene and integrity, and knowledge about volume frequency chart, selection and changing of pads seemed to be indulgent. Registered nurses showed slightly better results than the other groups, even if the differences were small. There were no significant differences between the care units, but the health care centre had the best total result as regards patient observations. CONCLUSION: The study confirmed that the nurses used faulty procedures to achieve quality of care. The study especially highlighted the role of nurses in primary health care, but since UI is a multidisciplinary symptom it demands interest and UI qualification of all personnel groups in the primary health care team. PMID- 7997696 TI - Why do only a minority of perimenopausal women with urinary incontinence consult a doctor? AB - OBJECTIVE: To investigate the reasons for not seeking treatment for urinary incontinence in perimenopausal women. DESIGN AND SUBJECTS: Postal invitation to participate in a telephone interview to a randomly selected 10% sample (n = 78) of women 40 to 50 years old in Namsos municipality, Norway. OUTCOME MEASURES: The interview guide included questions about symptoms of urinary incontinence, degree and type, past medical history, whether the women had consulted doctors or others for their illness and reasons for not consulting a doctor. RESULTS: 68 (87%) returned the answer slip, 67 were interviewed. 39 (58%) stated that they had urinary incontinence. 32 thought incontinence was normal at their age, and 33 claimed to have no social or practical inconveniences. Only 9 had consulted a doctor, of whom three had been referred to a gynaecologist. Analyses revealed no statistically significant differences between the women who had or had not consulted a doctor with respect to severity, type of incontinence, duration, or self-assessed psychosocial impact. The most common reason for not consulting a doctor was that the incontinence problem was regarded too small. CONCLUSION: More than half of the women said they had urinary incontinence. Fewer than a quarter of the 39 incontinent women had consulted a doctor. Simple quantitative measures concerning the woman and her illness do not seem fully to explain the mechanisms of non-consulting. PMID- 7997697 TI - Pregnancy--a golden opportunity for promoting the cessation of smoking? AB - OBJECTIVE: To investigate whether daily-smoking pregnant women are more motivated to reduce their cigarette consumption than daily-smoking non-pregnant women. DESIGN: Prospective study with self-administered questionnaires at inclusion and 18 months later. SETTING: 116 general practitioners in western Norway. SUBJECTS: 83 pregnant and 107 non-pregnant women. MAIN OUTCOME MEASURES: Non-anonymous questionnaires focusing on smoking habits and attitudes to smoking cessation. RESULTS: Pregnant women were more often encouraged to stop smoking by their partners than non-pregnant women (p < 0.01). More pregnant than non-pregnant women totally agreed that their GP should try to motivate their patients to stop smoking (p < 0.001). Pregnant women also predicted that they would be non-smokers in five years more often than non-pregnant women (p < 0.001). Eighteen months later no such difference was found. A reduced cigarette consumption, verified by serum thiocyanate, was found among women early in pregnancy. The reduced consumption found later in pregnancy and the first year after delivery may be explained to some extent by systematic underreporting. At the end of the study eight per cent of both pregnant and non-pregnant women had stopped smoking. CONCLUSION: We need to develop strategies for utilizing the unique opportunity which pregnancy provides for the motivation of cessation of smoking. PMID- 7997698 TI - Pros and cons of intrauterine contraception--do perceptions of users and physicians differ? AB - OBJECTIVE: To investigate women's and physicians' opinions of IUD use. DESIGN: Two cross-sectional postal surveys; on women in 1987-1988, on physicians in 1988. SETTING: Survey on women: southernmost Uusimaa province (including Helsinki). Survey on physicians: whole of Finland. PARTICIPANTS: Of a stratified random sample of 1000 women aged 18-44 years 84% returned the questionnaire (N = 844). Of a sample of 480 physicians (including GPs and gynaecologists) 418 were eligible, 74% of whom responded (N = 311). MAIN OUTCOME MEASURES: Women's and physicians' opinions of and experiences with IUD use as reported in postal questionnaires. RESULTS: Most women considered that IUDs were a good method of contraception. Users' and physicians' reports on benefits and disadvantages of IUDs metched each other; both most often mentioned ease of use, efficacy, and lack of systemic effects. Major disadvantages reported by women were bleeding, pain, infection, and pregnancy. Physicians further pointed to the risk of ectopic pregnancy. Though reports of side-effects were commonplace, there was reasonable satisfaction with IUD use. CONCLUSION: This study reveals that most women, and physicians, have a realistic picture of the common problems related to intrauterine contraception. It also emphasizes that, when making contraceptive choices, one is bound to compare possible disadvantages with benefits offered. PMID- 7997700 TI - Feasibility of comparing risk profiles for cervical cancer between participants and nonparticipants in a screening programme. AB - OBJECTIVE: Feasibility of comparing risk profiles by questionnaire of participants and nonparticipants in a cervical screening programme: does asking information on sexual behaviour by means of a questionnaire lead to high non response? is the non-response selective (related to participation in the screening) and if so how can we limit this? DESIGN: A postal survey on risk factors for cervical cancer, including sexual behaviour, in a group of participants and nonparticipants. SETTING: Two villages, Wijchen and Beuningen, situated near Nijmegen in The Netherlands. SUBJECTS: 139 participants and 99 nonparticipants in the national screening programme in 1989 or 1990. RESULTS: Overall, the response to the questionnaire was high: 83%. Collecting the questionnaire by asking the women to return it by mail in a stamped addressed envelope and one reminder by phone showed a response rate of 79%. This response was selective: 93% of the participants in the screening responded and 61% of the nonparticipants. Collecting them personally showed an extremely high response of 96% which was not selective. Only 3 respondents did not answer the questions about sexual behaviour. MAIN CONCLUSION: Obtaining information on sexual behaviour by questionnaire is feasible. Selective response can be limited by an extremely high response rate, which can be achieved by collecting the questionnaires personally. PMID- 7997699 TI - Signs of subclinical eating disorders in teenage girls. AB - OBJECTIVE: To study possible indicators for subclinical eating disorders among teenage girls. DESIGN: A descriptive cross-sectional study based on two anonymous self-report questionnaires. SETTING: Girls aged 15 to 19 years in secondary high school in Bergen, Norway. SUBJECTS: 100 girls, mean age 16.6 years, were included. One girl fulfilled DSM-III-R criteria for bulimia nervosa, and was therefore excluded from analysis. Ten girls fulfilled criteria for subclinical eating disorders. MAIN OUTCOME MEASURES: The Eating Disorder Examination Questionnaire and a 48-item questionnaire designed for the study were used. Attitudes towards own body size/weight, food habits, and somatic symptoms were studied. RESULTS: Girls with subclinical eating disorders experienced their own body as fatter and were more unhappy with their weight than girls without eating problems. They more often skipped breakfast or lunch, reported more dyspeptic problems and regurgitation, and had a larger weight fluctuation than girls without eating problems. CONCLUSION: Questions about main meals may serve as neutral opening questions for the general practitioner when case finding in eating disorders. Obviously unrealistic feelings about body size/weight indicate the need to enquire more closely about symptoms of eating disorders. PMID- 7997701 TI - Salaried and fee-for-service general practitioners: is there a difference in patient turnover? AB - OBJECTIVE: To compare use of working hours, patient turnover, and patient characteristics in two general practitioner groups which differed in contractual arrangements and income levels (partly fee-for-service vs. salary). DESIGN: Cross sectional study of all patient contacts during one week. PARTICIPANTS: All general practitioners (GPs) in Oslo (N = 263) with contracts with the municipality. 83% participated. MAIN OUTCOME MEASURE: Time spent in various types of work and patient turnover; the number of patients seen per hour of consultation time. RESULTS: Fee-for-service GPs worked almost exclusively with patients in their own practice, while salaried GPs spent more time out of office (consultation-based patient work constituting 55% of the working hours). The fee for-service group registered on average 2.68 consultations per hour of patient contact (95% confidence interval: 2.51-2.84). The corresponding numbers for the salaried group were 2.37 (2.24-2.50). Salaried GPs had somewhat more telephone consultations per hour (2.01 vs 1.66 for fee-for-service GPs), leaving a picture of two GP groups with small differences in patient turnover. The two patient populations were remarkably similar and so was the general practitioners' own evaluation of the consultations. CONCLUSIONS: Over a number of years the GPs in Oslo have practised under different contractual arrangements. As a consequence of different expectations and incentives it was expected that consultation activity and patient populations had evolved differently. This proved not to be the case. PMID- 7997702 TI - Referral notes used as a tool for evaluating the co-operation between general practitioners and hospital physicians. AB - OBJECTIVE: To study what proportion of clinical visits to a general practitioner working at a Swedish health centre leads to a referral to a specialist, the adequacy of the reason for the referral, the quality of the referral notes, and the quality of the answers by the specialists to whom the patients had been referred. DESIGN: A referee committee representing the different medical specialists and the general practitioners studied all referral notes dealing with internal medicine, surgery, orthopaedics, and otorhinolaryngology during a defined period from two health centres as to adequacy of the reason for referral, the quality of the referral notes, and the quality of the answers to the referrals. SETTING AND PARTICIPANTS: Altogether 188 consecutive referral notes and 171 answers to these referrals from two Swedish health centres were evaluated. RESULTS: Of the visits to a general practitioner, 7-8% resulted in a referral to a hospital specialist, and 90% of these were answered by letter. The referee committee agreed that the vast majority of the reason for referral were adequate, and that the referral notes as well as the answers to these with few exceptions were adequately formulated. CONCLUSIONS: The referrals from primary health care to different medical specialists worked adequately, but it was concluded that it may be further improved. When evaluating the co-operation between two medical systems, it is important that the evaluation as well is made in co-operation by representatives from the two systems. PMID- 7997703 TI - Fructosamine cannot replace HbA1c in the management of type 2 diabetes (NIDDM). AB - OBJECTIVE: To compare HbA1c, fructosamine, and blood glucose and discuss to what degree Hba1c can be replaced by fructosamine. DESIGN: Cross-sectional study. PATIENTS: 87 unselected patients coming for 112 consecutive consultations. MAIN OUTCOME MEASURES: Fructosamine, HbA1c, blood glucose. RESULTS: The following Pearson correlation coefficients were found: Blood glucose/fructosamine 0.45, HbA1c/blood glucose 0.64, and HbA1c/fructosamine 0.39. Sensitivity and specificity of fructosamine and blood glucose to detect HbA1c > or = 8.0% was shown. CONCLUSION: Our study indicates that fructosamine and fasting capillary blood glucose are poor indicators of the level of HbA1c in NIDDM patients. PMID- 7997705 TI - Testing for baseline balance in clinical trials. AB - Once the data from a clinical trial are available for analysis it is common practice to carry out 'tests of baseline homogeneity' on prognostic covariates before proceeding to analyse the effects of treatment on outcome variables. It is argued that this practice is philosophically unsound, of no practical value and potentially misleading. Instead it is recommended that prognostic variables be identified in the trial-plan and fitted in an analysis of covariance regardless of their baseline distribution (statistical significance). PMID- 7997704 TI - Helping doctors to draw appropriate inferences from the analysis of medical studies. AB - Most clinicians and many medical statisticians interpret standard frequentist confidence intervals by invoking the Bayesian concept of subjective probability. Fortunately, the assumptions that render this interpretation acceptable are often quite reasonable in the setting of the practical day-to-day analysis of medical data. This article takes the subjective interpretation of confidence intervals to its logical conclusion and argues that the inferential understanding of clinicians and public health physicians could potentially be improved if, where it was appropriate, standard inferential statements--point estimates, 95 per cent confidence intervals and P-values--were supplemented by estimates of the subjective posterior probability, assuming a uniform prior density, that the true value of a parameter to be estimated exceeds one or a series of thresholds that are clinically critical or easily interpretable. Many decision makers in the health care arena draw totally inappropriate inferences from analyses where the point estimate indicates a clinically valuable effect but the null hypothesis cannot formally be rejected, and, although the proposed approach could be of potential value in a range of settings, it is argued that it could be of particular use in the rational interpretation of underpowered studies that must inform critical clinical or public health decisions. PMID- 7997706 TI - An optimal three-stage design for phase II clinical trials. AB - A phase II clinical trial in cancer therapeutics is usually a single-arm study to determine whether an experimental treatment (E) holds sufficient promise to warrant further testing. When the criterion of treatment efficacy is a binary endpoint (response/no response) with probability of response p, we propose a three-stage optimal design for testing H0: p < or = p0 versus H1: p > or = p1, where p1 and p0 are response rates such that E does or does not merit further testing at given levels of statistical significance (alpha) and power (1--beta). The proposed design is essentially a combination of earlier proposals by Gehan and Simon. The design stops with rejection of H1 at stage 1 when there is an initial moderately long run of consecutive treatment failures; otherwise there is continuation to stage 2 and (possibly) stage 3 which have decision rules analogous to those in stages 1 and 2 of Simon's design. Thus, rejection of H1 is possible at any stage, but acceptance only at the final stage. The design is optimal in the sense that expected sample size is minimized when p = p0, subject to the practical constraint that the minimum stage 1 sample size is at least 5. The proposed design has greatest utility when the true response rate of E is small, it is desirable to stop early if there is a moderately long run of early treatment failures, and it is practical to implement a three-stage design. Compared to Simon's optimal two-stage design, the optimal three-stage design has the following features: stage 1 is the same size or smaller and has the possibility of stopping earlier when 0 successes are observed; the expected sample size under the null hypothesis is smaller; stages 1 and 2 generally have more patients than stage 1 of the two-stage design, but a higher probability of early termination under H0; and the total sample size and criteria for rejection of H1 at stage 3 are similar to the corresponding values at the end of stage 2 in the two-stage optimal design. PMID- 7997707 TI - Effect of verification bias on positive and negative predictive values. AB - The pairing of sensitivity and specificity expresses the efficacy of a test, and positive and negative predictive values measure the accuracy of a diagnostic test when applied to a particular patient. To calculate these measures, one has to know the true disease status of each patient. In practice, however, some patients may not be selected for verification of disease status. It has been shown that the estimated sensitivity and specificity may be biased if one includes in the study sample only the patients with verified disease statuses. This paper concerns the properties of the estimators of positive and negative predictive values using only patients with verified disease statuses. First, I show that these estimators are unbiased and provide consistent estimators for the variances of these estimators under the assumption that the probability of selecting a patient for a disease verification procedure does not depend directly on the true disease status of the patient. Then, I use the ML method to study the sensitivity of the naive estimators to the departure from the conditional independence assumption. PMID- 7997708 TI - Analysing survival in the presence of an auxiliary variable. AB - A primary endpoint of AIDS trials is the length of survival. Often there is auxiliary information available on measures of disease progression, which significantly alter the risk of mortality. This paper explores the use of this information in obtaining a refined estimate of survival, and a test based on this estimate. The methods are applied to an AIDS clinical trial, and results of simulations are provided which compare the approach to standard methods for survival analysis. PMID- 7997709 TI - Projection of incidence rates to a larger population using ecologic variables. AB - There is wide acceptance of direct standardization of vital rates to adjust for differing age distributions according to the representation within age categories of some referent population. One can use a similar process to standardize, and subsequently project vital rates with respect to continuous, or ratio scale ecologic variables. We obtained from the National Cancer Institute's Surveillance, Epidemiology and End Results (SEER) programme, a 10 per cent subset of the total U.S. population, country-level breast cancer incidence during 1987 1989 for white women aged 50 and over. We applied regression coefficients that relate ecologic factors to SEER incidence to the full national complement of county-level information to produce an age and ecologic factor adjusted rate that may be more representative of the U.S. than the simple age-adjusted SEER incidence. We conducted a validation study using breast cancer mortality data available for the entire U.S. and which supports the appropriateness of this method for projecting rates. PMID- 7997710 TI - Interval censoring in longitudinal data of respiratory symptoms in aluminium potroom workers: a comparison of methods. AB - In a longitudinal study of workers in seven Norwegian aluminium plants, the time to development of asthmatic symptoms could only be determined to lie in the interval between two consecutive health examinations. In a previous paper we analysed the data by survival techniques for interval censored data. In the present paper the data are reanalysed in two ways and compared to the previous analyses. First, it is assumed that occurrence of symptoms coincided with reporting, in which case the data can be analysed as right censored. Secondly, the follow-up times are completely disregarded and the effects of covariates are analysed on the binary outcomes of symptoms. Comparing the estimated effects of the covariates between the three approaches, only minor differences were found. However, the estimates on incidence were strongly influenced by whether the data were analysed as right or interval censored. PMID- 7997711 TI - Standardized rates of recurrent outcomes. AB - Longitudinal studies are often concerned with estimating the rate of an event that may recur. Examples are nonmelanoma skin cancer rates, screening rates for breast cancer using mammography and hospital admission rates. We propose simple estimators for directly and indirectly standardized summary rates and relative rates of recurrent events and their variances. We also develop an estimator of the excess rate in an area if the rate in another area applied. For non-recurrent events, the estimators are identical to the usual standardized summary rates. The estimators are independent of the underlying distribution of the event of interest and allow for unequal follow-up times and event rate heterogeneity among individuals. The method is not computationally intensive and does not require specialized software. We illustrate the application of the method in a retrospective cohort study of hospital utilization patterns of Medicare enrollees in Boston and New Haven over a three and a half year period. PMID- 7997712 TI - On the efficacy of the rank transformation in stepwise logistic and discriminant analysis. PMID- 7997713 TI - A comparison of two phase I trial designs. AB - Phase I cancer chemotherapy trials are designed to determine rapidly the maximum tolerated dose of a new agent for further study. A recently proposed Bayesian method, the continual reassessment method, has been suggested to offer an improvement over the standard design of such trials. We find the previous comparisons did not completely address the relative performance of the designs as they would be used in practice. Our results indicate that with the continual reassessment method, more patients will be treated at very high doses and the trials will take longer to complete. We offer some suggested improvements to both the standard design and the Bayesian method. PMID- 7997714 TI - Reduction in burden of illness: a new efficacy measure for prevention trials. AB - A new efficacy measure is developed for use in prevention trials of interventions which may affect both disease incidence and disease severity. We assign a severity score to each incident case and sum severity scores over all incident cases within each treatment group to create a burden-of-illness score for each treatment group. Efficacy is evaluated by the difference between the burden-of illness per randomized subject in the two randomized treatment groups. Since the numbers of summands in each burden-of-illness score is a random variable, standard methods of analysis are not directly applicable. The asymptotic distribution and sampling properties of the net reduction in the burden-of illness score are derived for trials designed to stop either after a fixed length of follow-up or after the occurrence of a fixed number of cases. We illustrate the method with data from a clinical trial of a human rotavirus vaccine. PMID- 7997715 TI - A unified method for monitoring and analysing controlled trials. AB - Group sequential methods are becoming increasingly popular for monitoring and analysing large controlled trials, especially clinical trials. They not only allow trialists to monitor the data as it accumulates, but also reduce the expected sample size. Such methods are traditionally based on preserving the overall type I error by increasing the conservatism of the hypothesis tests performed at any single analysis. Using methods which are based on hypothesis testing in this way makes point estimation and the calculation of confidence intervals difficult and controversial. We describe a class of group sequential procedures based on a single parameter which reflects initial scepticism towards unexpectedly large effects. These procedures have good expected and maximum sample sizes, and lead to natural point and interval estimates of the treatment difference. Hypothesis tests, point estimates and interval estimates calculated using this procedure are consistent with each other, and tests and estimates made at the end of the trial are consistent with interim tests and estimates. This class of sequential tests can be considered in both a traditional group sequential manner or as a Bayesian solution to the problem. PMID- 7997717 TI - Bayesian hierarchical analysis of within-units variances in repeated measures experiments. AB - We develop hierarchical Bayesian models for biomedical data that consist of multiple measurements on each individual under each of several conditions. The focus is on investigating differences in within-subject variation between conditions. We present both population-level and individual-level comparisons. We extend the partial likelihood models of Chinchilli et al. with a unique Bayesian hierarchical framework for variance components and associated degrees of freedom. We use the Gibbs sampler to estimate posterior marginal distributions for the parameters of the Bayesian hierarchical models. The application involves a comparison of two cholesterol analysers each applied repeatedly to a sample of subjects. Both the partial likelihood and Bayesian approaches yield similar results, although confidence limits tend to be wider under the Bayesian models. PMID- 7997716 TI - Deviance estimates of sample size for equivalence tests in vaccine trials. AB - This paper proposes a sample size procedure for both equivalence and conventional tests for the comparison of two binomial proportions, based on the signed square root of the deviance. When the comparison is based on the odds ratio, I describe an alternate 'close' conditional exact method that gives results that support those given by the deviance method. I summarize the advantages of the deviance based method and also show that in general equivalence situations the sample size estimate depends upon the measure of comparison selected, odds ratio, risk ratio or risk difference. PMID- 7997718 TI - Stratification of summary statistic tests according to missing data patterns. AB - Summary statistics, such as slope or area under the time-response curve, reduce the dimensionality of repeated measures data and can thereby simplify the comparison of groups in longitudinal studies. Since summary statistic distributions vary according to the amount, timing, and type of any missingness that occurs, one must choose between analysing the data unconditionally or conditionally on the missingness patterns. This paper uses simulations to compare such unstratified and stratified summary statistic analyses with respect to their size and power under models that allow for both non-informative and informative missingness mechanisms. Of particular interest is the robustness of these methods to violations of the assumptions that one must make if they are to have proper test size. It is found that stratification of the analysis tends to result in an increase of power, and improves the robustness to violations of missing data assumptions. PMID- 7997719 TI - Simultaneous back-projection of AIDS incidence data for two or more groups. AB - Back-projection of AIDS incidence data is useful for estimating characteristics of the HIV epidemic curve and forms a basis for projections of the AIDS epidemic curve. Its application to subgroups of the population is limited by its imprecision for groups with a small number of cases. Back-projection can be made more precise by pooling data from different groups and linking their HIV infection intensities by a model. Here we propose a method based on proportional infection intensities and study its performance with simulations and applications to AIDS in different States of Australia and haemophiliacs in the U.S.A. This method of simultaneous back-projection is shown to reduce substantially the width of confidence intervals for HIV infection intensities and for total numbers infected. PMID- 7997721 TI - Evaluating the role of CD4-lymphocyte counts as surrogate endpoints in human immunodeficiency virus clinical trials. PMID- 7997720 TI - Estimates of disease incidence in women based on antenatal or neonatal seroprevalence data: HIV in New York City. AB - Piecewise constant incidence models were developed to estimate the force of infection in women from age- and time-specific antenatal or neonatal seroprevalence data. Differential inclusion of infected women in sero-surveys compared to uninfected women was taken into account, with respect to both changes in inclusion rate following infection, and changes in relative inclusion rate over calendar time. These models were applied to anonymous HIV seroprevalence data collected from neonates born to black and Hispanic women in New York City 1988-1992, with incidence and fertility parameters estimated by maximum likelihood. Estimates of inclusion rate parameters accorded well with what is known about the natural history of HIV. The data could not distinguish between additive and multiplicative combination of the effects of age and time on incidence. Incidence was strongly dependent on age with the highest incidence in women aged 20-34 years. There was strong evidence that incidence had been falling in Hispanic women since 1982-1984. The results illustrate the extent to which trends in incidence over time may be confounded by changes in the relative inclusion rate of infected and uninfected women. PMID- 7997722 TI - The assessment and management of renal vascular hypertension after kidney transplantation. AB - The clinical setting that suggests transplant renal artery stenosis, its various forms, and the involvement of the renin-angiotensin system in its pathogenesis has been reviewed. Both captopril-enhanced renography and pulse duplex Doppler ultrasound are useful noninvasive screening tests for renal artery stenosis. Some form of angiography remains essential in defining the extent of the lesion and in planning therapy. Percutaneous transluminal angioplasty is the first-line therapy for most cases. Open surgical repair provides the most definitive treatment but has greater morbidity. Medical therapy alone is appropriate in patients with significant chronic allograft rejection or other comorbidities that preclude intervention for the renal artery stenosis. PMID- 7997723 TI - Genitourinary malignancies in organ transplant recipients. AB - The current recommendations for management of patients with pre-existing neoplasms before transplantation is a function of the cure rate achieved with the available therapeutic modalities and the risk of recurrence following initiation of immunosuppression. Recurrences after transplantation, as well as de novo malignancies, although unpredictable in many cases, have been identified as arising in certain individuals at risk and are a result of multifactorial etiologies. These etiologies include oncogenic effects of immunosuppressive agents or their broken-down metabolites, depressed immunity, dampened immune response, and activation of oncogenic viruses (herpes group, EBV), carcinogens, congenital predilection, and dormant residual cancers of high malignant potentials. Better understanding of the interplay of these factors and longer follow-up of transplant recipients receiving contemporary immunosuppressive agents are needed in order to diminish the likelihood of tumor recurrence/development in this population. Judicious application of current information obtained from the transplant registries, better understanding of immunosuppressive agents and their long-term oncogenic effects, and careful and conscientious allocation of cadaveric organs are advised. PMID- 7997724 TI - The diagnosis and management of urologic complications in nonrenal transplant recipients. PMID- 7997725 TI - Molecular determinants of soft tissue sarcoma proliferation. AB - Soft tissue sarcoma is an extremely rare malignant disease that includes more than 15 distinct histologic subtypes. While all share a propensity for metastasis to the lungs, the clinical presentation and pattern of spread for the specific subtypes are remarkably viable. Little is known about the etiology of soft tissue sarcoma other than several well described epidemiological associations between ionizing and other toxic agents and several of the soft tissue sarcoma histologic subtypes. The key to understanding the etiologic factors driving soft tissue sarcoma proliferation and dissemination lies in understanding the molecular mechanisms underlying these oncologic processes. Progress in this regard has been difficult because of the rarity of this disease. This report reviews the current state of knowledge for three of the most important considerations involving the molecular etiology of soft tissue sarcoma: growth factors and their receptors, nuclear and cytoplasmic oncogenes, and tumor suppressor genes. As we learn more about these molecular mechanisms leading to proliferation and dissemination of soft tissue sarcoma, molecularly based genetic therapies will become a reality for this all too devastating, albeit rare, disease. PMID- 7997726 TI - Diagnostic procedures and pretreatment evaluation of soft tissue sarcomas. AB - The diagnosis and preoperative evaluation of patients with a suspected soft tissue sarcoma involve several important considerations to ensure optimal treatment outcomes. Biopsy techniques must involve the retrieval of adequate tissue to establish the histologic diagnosis and grade of the tumor without compromising the subsequent definitive surgical resection. CT or MRI techniques represent the gold standard to evaluate the local extent of disease which is necessary to ascertain surgical resectability and/or the need for radiation therapy. CT scanning of the lungs is mandated for all patients with sarcomas to evaluate for metastatic disease and, for patients with abdominal or retroperitoneal tumors, scanning of the liver should also be included. Accurate staging of these patients will help define overall survival. PMID- 7997727 TI - Operative management of soft tissue sarcomas: impact of anatomic site. AB - Operative management of soft tissue sarcomas begins with the surgical biopsy. Incisional biopsy of an undiagnosed soft tissue mass allows optimal later definitive resection, this resection including the entire biopsy wound, as well as accomplishing an "adequate" margin around the sarcoma. The principles employed for this resection are those that lead to adequate gross and microscopic margins of normal tissue around the sarcoma while considering the limitations, in terms of physical disability, from the procedure itself. This operative strategy is described for various anatomic locations, such as the extremities, trunk, retroperitoneum, and head and neck; special problems with each of these primary sites are discussed. PMID- 7997728 TI - Role of radiation in the management of adult patients with sarcoma of soft tissue. AB - Radiation in moderate dose levels, viz. 60-65 Gy at 2 Gy/fraction, administered in combination with conservative surgery, yields local control frequencies at least comparable to those achieved by radical resectional surgery alone. The clinical interest in this management strategy is the reduction in the scope of the resection and a consequent gain in cosmetic and functional status. This combined approach is favored for sarcomas so situated that resection with wide margin, > or = 2 cm at the most narrow, cannot be realized unless there is a clinically important loss in function. Where radical surgery is planned, there must be great care in assessment of the probability of achieving good margins. The patient is ill served if there is radical surgery and then, because of close margins, postoperative radiation is required. There appears to be clinical gain for the patient with a large sarcoma by administering the radiation preoperatively. Advantages include smaller treatment volume and higher local control rates. The management of the surgical wound in the irradiated patient is discussed. Also, brief consideration is given to current use of brachytherapy, high linear energy transfer (LET) radiation, and combination of radiation and chemotherapy. PMID- 7997729 TI - Chemotherapeutic approaches to soft tissue sarcomas. AB - Conventional chemotherapy for adult type soft tissue sarcomas is not very effective. Rarely are patients with advanced soft tissue sarcomas curable by systemic chemotherapy. Thus, the benefits from chemotherapy have been equivocal even when treatment is given postoperatively to patients whose primary sarcomas have been excised. Current research is directed toward the achievement of a high percentage of complete tumor regressions in patients with advanced metastatic disease in hope that this can be translated into truly effective adjuvant therapy. Several recent new approaches to systemic treatment for soft tissue sarcomas are assessed including prospects for possible enhancement of chemotherapy by agents which stimulate cellular immunity. Some unexpectedly favorable responses to chemotherapy+granulocyte-macrophage colony-stimulating factor (GM-CSF) in an ongoing study are discussed. PMID- 7997731 TI - Gynecological sarcomas. AB - Sarcomas of the uterus, ovary and lower genital tract are fortunately rare, since the prognosis is quite often poor. The most frequent are sarcomas of the uterine corpus, and these account for only 4% of all uterine tumors. Ovarian sarcomas are less frequent, and the prognosis is even poorer when compared to the uterus. Sarcoma of the lower genital tract (vagina and vulva) in adults is often published as a case report, given their very infrequent occurrence. PMID- 7997730 TI - Retroperitoneal sarcomas. AB - Retroperitoneal sarcomas are rare malignant tumors, accounting for approximately 10-20% of all soft tissue sarcomas. Because of their anatomic location and indolent nature, these tumors are usually quite extensive when first detected with little hope of improvement in the early detection rate. Improved survival rates will therefore depend on obtaining better local control through an aggressive surgical approach, making every effort to achieve a complete resection with histologic negative margins, which in most cases will require the resection of adjacent organs or vascular structures. Even with such aggressive surgical approach, continued problems with local recurrence are reported and it is important to follow patients who had undergone surgical resection very carefully in order to identify those who would benefit from reresection. The results of postoperative adjuvant irradiation and/or chemotherapy have so far been discouraging. Until there is a national registry and a national intergroup study to develop strategies and innovative trials for the effective treatment of these tumors, it is unlikely that there will be much improvement in the current survival rates. PMID- 7997733 TI - [Immunity, inflammation and atherosclerosis]. AB - Atherosclerotic plaques harbour 3 main cell types: arterial smooth muscle cells, monocyte-macrophages and T-lymphocytes. Together with other morphological characteristics, this feature concurs to the view that plaques are foci of chronic inflammation. The presence of T-cells suggests that immune mechanisms are involved in the development of atherosclerosis. Clinical studies have found correlations between the presence or progression of carotid plaques and the serum concentration of antibodies against oxidized low-density lipoproteins and against heat shock protein HSP-65. Along with other observations, these correlations, if confirmed and extended, may open new avenues to understand the triggering mechanisms of atherosclerosis. However, the available evidence is still insufficient to establish that an autoimmune involvement is a cause rather than a consequence of atherosclerosis. PMID- 7997732 TI - Sarcomas related to the heart and vasculature. AB - Soft tissue sarcoma is the most common malignant neoplasm of the heart, pericardium, and great vessels. Its presentation is infrequent, nonspecific, and subtle. For example, emboli from these tumors to the lungs or peripheral arteries may mimic thrombotic embolic disease. New noninvasive techniques such as echocardiography and magnetic resonance imaging (MRI) aid in diagnosis and preoperative assessment. Angiosarcoma, the most common cardiac sarcoma, is aggressive and usually arises in the right atrium. Kaposi's sarcoma of the heart has been found in patients with AIDS and in immunosuppressed organ transplant recipients. Most primary sarcomas of the aorta and pulmonary artery (the elastic arteries) show minimal differentiation and are classified as "intimal, sarcomas," whereas leiomyosarcomas predominate in the muscular arteries and great veins. Surgical resection of any sarcoma of the vasculature, when feasible, is technically challenging but may result in cure or palliation. Adjuvant chemotherapy and radiation therapy can also relieve symptoms and prolong survival. PMID- 7997734 TI - [Treatment of tremor by stereotactic surgery]. AB - Thalamotomy in the ventrolateral thalamic nucleus is a common treatment of severe parkinsonian or essential tremor. Although results are often satisfactory, complications may occur and alter the success of the operation. High frequency stimulation of the target before thalamotomy leads to transitory abolition of the tremor. Therefore, a chronic stimulation device was developed and its use produced results similar to those of thalamotomy for parkinsonian tremor. Unwanted side-effect can be reduced by changing the parameters of the stimulation. Improvements in multiple sclerosis and post-traumatic tremors may be expected. We present a review of the indications and results of both technics. PMID- 7997735 TI - [Babinski and movement synergism]. AB - Babinski's hypothesis that the cerebellum plays an important role in controlling movement synergies is re-interpreted in the light of more recent neurophysiological data. Originally Babinski derived the concept of synergy from the study of movement kinematics, but today, synergy implies an underlying combination of simultaneous muscular activities. It is suggested that the fundamental unit of muscular synergy is the reciprocal inhibition or the co contraction of antagonist muscles. Various experimental data suggest that an increase in Purkinje cell discharge decreases muscular activity and relaxes antagonist muscles. Inversely, a decrease of cerebellar cortical efferent activity increases nuclear excitability and as a result the long descending motor pathways. Consequently the cerebellum, by controlling joint stiffness through the level of co-contraction in antagonist muscles, would have a significant action in directing multi-joint movement and postural adjustments. PMID- 7997736 TI - [Value of TE671 cells in the detection of anti-acetylcholine receptor antibodies]. AB - The measurement of antibodies directed against the cholinergic receptor, produced by myasthenic patients, involves a radioimmunoassay. The use of human muscular nicotinic cholinergic receptor is highly recommended for this assay. However, difficulties in supplying and standardizing this reagent led us to consider its replacement by the homologous cholinergic receptor constitutively expressed by the human cell line TE671. TE671 cells were grown in mass cultures on microcarriers and acetylcholine receptors were solubilized using detergents. Replacement of human muscular receptor by cellular receptor in the radioimmunoassay assay was assessed by challenging these 2 antigens for numeric or diagnostic correlations. Using TE671 receptor, the correlations observed were good and, despite a slight decrease in the absolute values of the titers, about 90 p. 100 of the assays provided the same diagnostic accuracy. Some interfering proteins, perhaps immature acetylcholine receptor alpha subunits, could be expressed and could account for the slight decline in the antibody titers obtained using TE671 receptor. These interferences could be overcome by a further step of purification and concentration of the various receptor preparations. Finally, TE671 receptor could definitely replace human muscular receptor for screening and measuring myasthenic patients auto-antibodies. PMID- 7997737 TI - [Approach to chronic cerebellar diseases in children]. AB - Cerebellar pathology in infants falls into two parts. The pathology that is accessible to a molecular approach is represented mainly by monogenic metabolic diseases of postnatal expression while the pathology that remains descriptive is represented mainly by congenital disorders of cerebellar development. These disorders may be associated with a variety of abnormalities defining a rapidly increasing number of syndromes. Identification of the numerous morphogenes involved in cerebellar development will probably result not only from extrapolation to man of homologous recombinations experiments but also from genetic investigations in exceptional clinical cases. PMID- 7997738 TI - [Alexander's disease in adults and diffuse cerebral gliomatosis in 2 members of the same family]. AB - A 31-year old woman died after 10 years of progressive dysautonomia and cerebellar and pyramidal symptoms. CT scan showed pontine, bulbar and cerebellar atrophy. Post-mortem examination revealed Rosenthal's fibers widespread throughout the CNS, but especially in the subependymal and perivascular regions. White matter cavitations involving peri-ventricular regions, hilum of dentate nuclei and pons were observed, leading to a diagnosis of adult form of Alexander's disease. At the age of 5, the patient had been operated upon for a chiasmatic tumor. Microscopic examination revealed a pilocytic astrocytoma without Rosenthal's fibers. No complementary radiotherapy had been done. Her mother has been operated upon in 1972, for a high-grade glioma and is still alive 20 years later. This suggests diffuse cerebral gliomatosis. This family history may suggest a relation between these different diseases. They might be the result of a transmissible astrocytic abnormality with varying expression. PMID- 7997739 TI - [Limb-girdle syndrome. A study of 46 cases]. AB - We report a series of 46 patients (32 women and 14 men) with limb-girdle syndrome. After reappraisal, another diagnosis was made in 10 of them. Becker's muscular dystrophy was the most frequent cause among men (near 50 p. 100). A Duchenne muscular dystrophy manifesting carrier was discovered among 13 reevaluated women. Among the 36 cases (29 women and 7 men) without any defined etiology, 29 were without any other known familial history. Fifteen of these women had similar clinical findings: incipient weakness in the pelvic girdle and onset of symptoms most often in the forties. In these cases serum creatine kinase activity was normal or slightly elevated, and muscle biopsy showed non-specific patterns. "Late onset muscular dystrophy in females" should be reevaluated. PMID- 7997740 TI - [Visual perseveration and palinopsia: a visual memory disorder?]. AB - Visual perseveration and palinopsia are defined as the persistence or the reappearance of the visual image. These infrequent symptoms are thought to be linked to the right hemisphere posterior areas. We report a case of this syndrome in which the initial fixation was foveal. The palinoptic image was sometimes moving. This suggests that palinopsia is due to a dysfunction of the visual memory, rather than of the visual system: this dysfunction may be related to hyperactivity of the visual buffer. PMID- 7997741 TI - [Type II carnitine palmitoyl transferase deficiency complicated by acute respiratory failure]. AB - Carnitine palmitoyl transferase (CPT) deficiencies can realise distinct clinical presentations. The best known is the muscular form with episodic muscle necrosis and paroxysmal myoglobinuria after prolonged exercise, in young adults, and results from decreased CPT II activity. In this paper, we report on an observation of a patient with a severe CPT II deficiency who presented a respiratory failure during an attack of muscle necrosis. The severity of the symptomatology were associated with a conspicuous reduction of CPT II residual activity in leucocytes and in fibroblasts. Fasting test showed an hypoketogenesis. These results support the concept that CPT II deficiency is ubiquitous, even though injury is restricted to the skeletal muscle. PMID- 7997742 TI - [Oculomotor disorders caused by thalamo-peduncular infarction after vertebral artery dissection]. AB - A case of left vertebral artery dissection after neck manipulation associated with an ipsilateral thalamo-peduncular infarct by distal embolism is reported. The oculomotor signs observed are explained for the left eye by an intra-axial third nerve lesion, and for the right eye by a limitation of the horizontal gaze to the right and an upgaze palsy of supranuclear origin. The association of infra and supranuclear lesions without nuclear lesion in thalamo-peduncular infarcts is considered. PMID- 7997744 TI - [Cerebellar syndrome after carbon monoxide poisoning. Magnetic resonance imaging and single photon emission tomography]. AB - A 19-year-old woman presented with severe carbon monoxide poisoning resulting in coma, brain stem signs, cerebellar syndrome, anterograde memory disorder and some frontal signs. Nine years later, generalized seizures appeared. At the age of 31, the cerebellar syndrome and memory disorders persisted. MRI showed cerebellar and internal temporal atrophy with high-intensity signals, and hippocampal and callosal atrophy. SPECT (Xe133) showed a low cerebellar blood flow. PMID- 7997743 TI - [Normal pressure hydrocephalus and lumbar neurinoma]. AB - A 76-year-old man presented with gait disturbances, mental deterioration and urinary incontinence. CT and MRI suggested a normal pressure hydrocephalus. Because of a raised protein content of CSF, a spinal MRI was performed and revealed a lumbar neurinoma. The patient improved after removal of the neurinoma and ventricular derivation. PMID- 7997745 TI - [Late disclosure of intra-cerebral epidermoid cyst]. AB - Symptoms of right hemisphere dysfunction had developed over a 10-month period in a 69-year old woman. She had experienced transient episodes of facial asymmetry for 10 years. CT scan showed a hypodense hourglass tumor extending above and below the tentorium. MRI showed a low-intensity signal with T1-weighted sequences and a high-intensity signal with T2-weighted sequences. The tumour was removed. Pathological examination proved the tumor to be an epidermoid cyst. Such a tumor may have been responsible for transient deficits in the late stages of development. PMID- 7997746 TI - [Paralysis of abdominal muscles caused by Lyme disease]. AB - A 67-year old patient with meningoradiculitis due to Borrelia Burgdorferi presented with unilateral trunk dysesthesias and severe asymmetrical abdominal distension. The causes of abdominal wall paralysis are reviewed. PMID- 7997747 TI - [Association of post-radiation focal muscular atrophy and hypertrophy]. AB - We report a 48 year old woman who had radiotherapy for uterine carcinoma and who developed amyotrophy and muscle hypertrophy in one lower limb. Very few cases of post-radiation monomelic amyotrophy have been reported. On the other hand denervation hypertrophy was presumed to be well known. The seat of the lesions was presumed to be radicular and spinal. The mechanism of atrophy and hypertrophy is discussed. PMID- 7997748 TI - [Confrontation at Salpetriere hospital. January 1992. Progressive athymhormia in a 30-year-old woman]. PMID- 7997750 TI - [Geographic distribution of Lutzomyia verrucarum (Townsend, 1913) (Diptera, Psychodidae, Phlebotominae), vector of human bartonellosis in Peru]. AB - Lutzomyia verrucarum (Townsend, 1913) (Diptera: Psychodidae); the natural vector of Bartonella bacilliformis, agent of human bartonellosis (peruvian verruga or Carrion's disease), is a native species of Peru; its geographic distribution occurrs between latitudes 5 degrees and 13 degrees 25' South: in the Occidental and Interandean valleys of the Andean. The altitudinal distribution of Lu. verrucarum in the different valleys is as follows: Occidental between 1100 and 2980 m sea level and Interandean from 1200 to 3200 m sea level. Some discrepancies between the distribution of Carrion's disease and Lu. verrucarum suggest the existence of secondary vectors in certain areas where Lu. verrucarum is not present. PMID- 7997751 TI - [Community participation and appropriate technology in the early diagnosis of human hydatidosis]. AB - The basic strategy for development of hydatid struggle programs is in the actuality: Primary Attention of Health. In the present work and in this instance, it's arm a precocious detection system of hydatid disease, fixed in immunologic diagnostic by means of ELISA technical beginning with blood capillary samples, taken in filter paper by teachers and sanitary agents from official services of Rio Negro Province. 177 teachers and 45 sanitary agents were trained, correspondent to 25 schools, 3 lodging schools and 9 Hospitals all of them from rural area. 890 blood samples during the training were obtained. Lastly, the trained personal armed the system and they obtained 728 samples in the beginning of the Program. It hadn't statistical differences in the reactivity of both samples. The serological prevalence found was 1.32%. The activity displayed by teachers and sanitary agents permitted to detect 21 new cases it was the 20% of new cases diagnosed in this area in the period of work. The viability and the importance of the incorporation of non traditional effectors into the Hydatid Control Programs is discussed. PMID- 7997749 TI - Regional variation in toxoplasmosis seronegativity in the Sao Paulo metropolitan region. AB - Toxoplasmosis is a highly prevalent zoonotic human infection caused by the Apicomplexa protozoon Toxoplasma gondii. The acute disease is usually mild or asymptomatic, except for foetal infection transmitted by acutely infected pregnant women, which courses as a devastating disease. In order to determine possible regional variations in risk factors, we studied the frequency of seronegativity in areas of the Sao Paulo Metropolitan Region, comparing titers and age groups. The prevalence of seronegativity was determined retrospectively in 1286 pregnant women receiving prenatal care at public health services in four selected areas of the Sao Paulo Metropolitan Region of similar socioeconomic background. The Sao Paulo City area had the higher frequency of seronegativity (41.1%), followed by the Northwest (31.5%) and Southwest (29.9%) areas, with similar intermediate levels, and by the Northeast (22.5%) area with the lowest frequency (p < 0.001). A rough estimate disclosed about 280 infected infants/year in the Sao Paulo Metropolitan Region. Serological titers analyzed by age group suggested a decline in antibody levels with age, as shown by a lower frequency of higher titers in older groups. Our study emphasizes the importance of determining the regional prevalence of toxoplasmosis for proper planning of public health prenatal care. PMID- 7997752 TI - Malaria serology: performance of six Plasmodium falciparum antigen extracts and of three ways of determining serum titers in IgG and IgM-ELISA. AB - The study evaluated six Plasmodium falciparum antigen extracts to be used in the IgG and IgM enzyme-linked immunosorbent assays (ELISA), for malaria diagnosis and epidemiological studies. Results obtained with eighteen positive and nine negative control sera indicated that there were statistically significant differences among these antigen extracts (Multifactor ANOVA, p < 0.0001). Urea, sodium deoxycholate and Zwittergent antigen extracts performed better than did the three others, their features being very similar for the detection of IgG antibodies. Urea, alkaline and sodium deoxycholate antigen extracts proved to be better than the others for the detection of IgM antibodies. A straight line relationship was found between the optical densities (or their respective log10) and the log10 of antibody dilutions, with a very constant slope. Thus serum titers could be determined by direct titration and by two different equations, needing only one serum dilution. For IgM antibody detections, log10 expression gave results that better correlated with direct titration (95% Bonferroni). For IgG antibody detections, the titer differences were not significant. The reproducibility of antibody titers and antigen batches was also evaluated, giving satisfactory results. PMID- 7997753 TI - An attempt at reversibility and increase of the virulence of axenic strains of Entamoeba histolytica. AB - In this study we have tried to verify whether the interaction "in vitro" with bacteria or small pieces of normal hamster liver would modify the pathogenic behavior of axenic strains of E. histolytica: avirulent ones (ICB-32 and ICB RPS), of attenuated virulence (ICB-CSP and HM1) and of mean virulence (ICB-462). Every attempt to render virulent, recover or increase the virulence of axenic strains of E. histolytica has failed. PMID- 7997754 TI - [Preliminary trials of Guaiacum officinale L. as a molluscicide]. AB - Aqueous suspensions of fruit's pericarp, leaves, root's bark and seeds of Guaiacum officinale were tested at different concentrations as molluscicide, cercaricide and piscicide. In the laboratory the suspension of fruit's pericarp produced 100% mortality for egg masses of B. glabrata at 100 ppm, for adult snails of Biomphalaria glabrata, B. straminea and B. tenagophila at 20 ppm, for Lebistes reticulatus (fishes) at 5 ppm and Schistosoma mansoni's cercariae at 1 ppm. The ethanolic extract of fruit's pericarp was not active against adult snails of B. glabrata. The lethal dose for adult snails(DL90) of the aqueous suspension of fruit's pericarp after 24 hours exposure, were: 15 ppm for B. glabrata; 14 ppm for B. straminea and 18 ppm for B. tenagophila. The DL90 of aqueous suspensions of root's bark, seeds and leaves were 57 ppm, 33 ppm and 15 ppm, respectively. In the field, B. glabrata adult snail mortality was 68% at 20 ppm and 100% at 40 ppm, when using suspension of fruit's pericarp. PMID- 7997756 TI - [Laboratory-acquired human infection with SP H 114202 virus (Arenavirus: Arenaviridae family): clinical and laboratory aspects]. AB - Here in is described the clinical and laboratorial findings of a laboratory acquired infection caused by the virus SP H 114202 (Arenavirus, family Arenaviridae) a recently discovered agent responsible for a viral hemorrhagic fever. The patient was sick for 13 days. The disease had an abrupt onset characterized by high fever (39 degree C.), headache, chills and myalgias for 8 days. In addition, on the 3rd day, the patient developed nausea and vomiting, and in the 10th, epigastralgia, diarrhea and gengivorrhagia. Leucopenia was seen within the 1st week of onset, with counts as low as 2,500 white cells per mm3. Counts performed after the 23rd day of the onset were within normal limits. With the exception of moderate lymphocytosis, no changes were observed in differential counts. An increase in the titer of antibodies by complement fixation, neutralization and ELISA (IgM) was detected. Suckling mice and baby hamsters were inoculated intracerebrally with 0.02 ml of blood samples collected in the 2nd and 7th days of disease. Attempts to isolate the virus were also made in Vero cells. No virus was isolated. This virus was isolated before in a single occasion in Sao Paulo State, in 1990, from the blood of a patient with hemorrhagic fever with a fatal outcome. The manipulation of the virus under study, must be done carefully, since the transmission can occur through aerosols. PMID- 7997755 TI - Detection of hepatitis B virus DNA by the polymerase chain reaction in anti-HBe positive chronic hepatitis B patients. AB - Detection of HBV-DNA by PCR was compared with other serological markers (HBsAG, HBeAg and anti-HBe) in a series of 49 Chronic Hepatitis B patients, including 12 with a spontaneous clearance of HBsAg. None of these HBsAg negative cases were PCR positive, but 33/37 (89.2%) HBsAg positive cases were PCR positive (p < 0.0001). Among HBsAg positive samples, nine cases were HBeAg positive and anti HBe negative, all of them PCR positive. Other 3 patients were HBeAg and anti-HBe positive and these cases were also found PCR positive. A third group included 21 patients anti-HBe positive and HBeAg negative: 19 of them were PCR positive and 2 were PCR negative. The last 4 cases were HBeAg and anti-HBe negative, two of them were PCR positive. The detection of anti-HBe viremic cases in the present series suggest that preC variants could occur in our country. In conclusion, the integrated phase of chronic hepatitis B seems to be less frequent than it was assumed, when only HBeAg or dot blot hybridization techniques were used. The new term "low replication phase" might favorably replace the former "integrated phase". PMID- 7997757 TI - [Characterization of the minimal lethal dose of gamma irradiation for Penicillium citrinum]. AB - The use of nuclear power through radiation for the destruction of microorganisms which cause food decay, and toxicosis, is specifically for peaceful purposes. Penicillium citrinum is a fungus which produce mycotoxins responsible for intoxication in humans and animals as a result of eating contaminated food. There is little informations on the resistance of P. citrinum to radiation. The objective of this research is to determine the lethal dose of gama radiation for these microorganisms. Seventy six suspensions containing approximately 100,000 spores/ml received a dose of radiation between 0.2 and 2.2 KGy (KiloGray), being one sample still alive re-irradiated with doses up to 3.0 KGy. The fungus were totally destroyed with a 2.2 KGy. Seventy six suspensions containing approximately 100,000 spores/ml received a dose of radiation between 0.2 and 2.2 KGy, being one sample still alive re-irradiated with doses up to 3.0 KGy. The fungus were totally destroyed with a 2.2 KGy dose. An increase in the resistance to lower dose levels of radiation was observed, in relation to the fungus which had not received irradiation. CONCLUSION: the Minimum Lethal Dose (MLD) of gamma irradiation, for P. citrinum is 2.2 KGy; the re-irradiation of the surviving fungus demonstrate that occur appearance of radio-resistant mutants. PMID- 7997758 TI - [Comparative study of the pathogenicity and antigenicity of 6 Paracoccidioides brasiliensis strains]. AB - A comparative study of antigenicity and pathogenicity for rats of six Paracoccidioides brasiliensis strains was carried out. The antigenic capacity "in vitro" of cytoplasmic extract from each strain was determined by immunodiffusion test against 6 serum samples obtained from rats experimentally infected with Paracoccidioides brasiliensis, that had presented positive reactions with a metabolic control antigen. The cytoplasmic extracts were used at final concentration of 100 mg/ml. All of them showed 2 or 3 precipitation bands in this assay. One hundred twenty Wistar rats both sexes weighing approximately 200 g, were inoculated intracardiacally with suspensions of the yeast phase of different P. brasiliensis strains. Two concentrations containing 3 x 10(7) and 5 x 10(7) cells/ml of each isolate were prepared. The inoculated animals were divided in two groups, one was left to its spontaneous outcome and the percentages of deaths were registered and the other rats were sacrificed at 14, 28, 56 and 70 days post infection. The following parameters were taken into account for evaluation: A) presence of macroscopic granulomas in lung, liver, spleen and kidney; B) presence of P. brasiliensis in microscopic exams of the same organs, in wet preparations and in histologic sections stained by H&E; C) culture of lung and D) immunodiffusion test using pre-mortem serum samples and the homologous antigen. The correlation between the most important parameters studied in each strain are summarized as follow: As no significant differences between the two inocula employed for each strain was observed, the before mention results are the average of those obtained with each inoculation doses.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7997759 TI - [Counterimmunoelectrophoresis technique for determining the antigenic potency of rabies vaccine]. AB - The method recommended by the World Health Organization (WHO) for the potency assay of human and animal rabies vaccines as final product is the NIH test. Some in vitro techniques have been proposed for in process testing and supplement the in vivo test mentioned above. This paper presents the results obtained when using a counterimmunoelectrophoresis (CIE) techniques to determine the antigens content in samples of 84 and 40 samples of lots of suckling mouse rabies and tissue culture rabies vaccines, respectively. The evaluation of rabies vaccines under, at, near and up to 0.3 UI by the NIH and CIE tests showed that for practical use, a CIE titer of 1:4 would match the minimum of NIH potency test requirement. Low degree of CIE test variability within our laboratory was observed, when two working reference and 7 lots of rabies vaccines from different origin and activity were tested in five independent assays. All titres fell within one double dilution what is an indication of its reproducibility. Good sensitivity to detect antigen deterioration in thermal degradation test was observed when samples of 3 lots of liquid suckling mouse rabies vaccine were held stored at 4 degrees C or at 37 degrees C for 4 weeks and assays by CIE and NIH tests. Finally, CIE test could apply by manufactures to follow the concentration procedures to determine the final end point which could match a desired antigenic value in the NIH potency test. PMID- 7997761 TI - Schistosoma mansoni: evaluation of the activity of oxamniquine on schistosomules, at 24 hours after infection. AB - Mice transcutaneously infected with about 400 cercariae were submitted to treatment with oxamniquine (400 mg/kg), 24 hours after infection. The recovery of schistosomules, at 4, 24, 48 and 72 hours and 35 days after treatment, showed the activity of the drug on the parasites, thus practically preventing their migration from the skin to the lungs. Worm recovery performed in the lungs (96 hours after treatment) showed recovery means of 0.6 worms/mouse in the treated group and 53.8 in the control group (untreated). The perfusion of the portal system carried out at 35 days after treatment clearly showed the elimination of all the parasites in the treated group, whereas a recovery mean of 144.7 worms/mouse was detected in the control group (untreated). These findings confirm the efficacy of oxamniquine at the skin phase of infection, and also show similarity with the immunization method that uses irradiated cercariae. The practical application of these findings in the medical clinic is discussed too. PMID- 7997760 TI - [Staphylococcal coagglutination reaction in the identification of mycoplasma]. AB - Staphylococcal Coagglutination was used as method for a rapid identification of mycoplasmas that could be performed by non specialized laboratories. Suspensions of Staphylococcus aureus (Cowan I) sensitized with rabbit antibodies against NCTC mycoplasma strains have identified these microorganisms and the strains isolated from humans, cell cultures rats and mice in concentrated suspensions from cultures of 4.0 ml. Fourty eight strains of M.pulmonis, 6 of M. arthritidis, 8 of M.arginini, 3 of M.orale, 15 of A.laidlawii, 8 of M.hominis and 3 of M.pneumoniae were identified by staphylococcal coagglutination and confirmed by Growth Inhibition Test. Optimal parameters of coagglutination were established and the stability of the conjugates were preserved for 90 days when added with acetyl cysteine. The reaction was visualized without optical resources. The sera were previously absorbed with heterologous NCTC strains and with the pellet of the sterile broth. PMID- 7997762 TI - [Health education in 1st grade public schools at the periphery of Belo Horizonte, MG, Brazil. I. Evaluation of the program relative to schistosomiasis]. AB - A project has been developed with the objective of implanting and testing new materials and methodologies related to health education in first level schools. The present study is being performed in 4 public schools of a periferic area of Belo Horizonte, in two regions, one of high and another of low prevalence of schistosomiasis. The experimental design includes 2 experimental schools and 2 of control. The procedure involves interviews with teachers and students before and after the experimental test of the new materials; stool surveys and treatment of the sample of students. The results of the first interviews demonstrated that the knowledge of schistosomiasis is almost absent among teachers and students, although the prevalence of this disease has been maintained for a long time (70 years) in one of the regions studied (Gorduras). Out of 3131 students of the 4 schools, 67.5% were examined and 235 (11.0%) were tested positively. When the new students of 1989 were not included the prevalence decrease to 9.0% demonstrating a significative difference (X2 - 5%) in relation to 1988, showing the consequence of the treatment performed. Comparing the 2 schools of high prevalence, the decrease of prevalence of the experimental one is higher than the control. Therefore, in relation to the schools of low prevalence, the same has not happened. Thus, it is only possible to suggest an initial effect of the educative strategy and the decreases of the prevalence in the schools of high prevalence. In relation to the knowledge about the disease transmission, the students from the experimental schools presented a significative increase of correct answers in 1989 than the control ones. PMID- 7997764 TI - Entamoeba histolytica zymodemes in children of Osasco, Sao Paulo. PMID- 7997763 TI - [Health education in 1st grade public schools at the periphery of Belo Horizonte, MG, Brazil. II. Knowledge, opinion and prevalence of helminthiasis among students and teachers]. AB - As part of a wide ranging project concerning education and health, aiming both to update and develop new materials and methods for 1st Grade schools, the present study investigated the state of knowledge and prevalence of helminthic diseases in school populations. Interviews and parasitological exams undertaken in four schools (two experimental and two controls) on the outskirts of Belo Horizonte showed: a. that both teachers and pupils have little information concerning helminthic diseases as well as incorrect notions and ignorance of the mechanisms of transmission; b. high prevalence in the school: 69.0% and 76.0% (Bairro Gorduras) and 46.0% and 24.0% (Vale do Jatoba and Barreiro de Cima) in the first year of study (1988). Comparing the four schools, there is a direct relationship between the living conditions of the pupils and the indices of prevalence. Considering the fact that such helminthic diseases are known to have been present for a long time, it is a striking how removed the school is from the problems and realities of its pupils. PMID- 7997765 TI - Report on a visceral and cutaneous leishmaniases focus in the town of Jequie, State of Bahia, Brazil. PMID- 7997767 TI - Evaluation of three chemotherapeutic schemes with meglumine antimoniate in the treatment of visceral leishmaniasis in the State of Para, Brazil. PMID- 7997766 TI - [Cardiac arrhythmia with oral oxamniquine use in the schistosomiasis mansoni treatment]. AB - The authors report a case of a patient with schistosomiasis (S. mansoni) treated with one single dose (15 mg/kg/BWT) of oral oxamniquine who presented Mobitz type I second-degree AV block and sinus arrest with ventricular escape as a side effect. They conclude that in spite of the safety and good activity of oxamniquine it may be a determinant of cardiotoxicity. PMID- 7997768 TI - Decreased erythrocyte osmotic fragility during canine leptospirosis. AB - Erythrocyte osmotic fragility (EOF) was carried out in nineteen dogs naturally infected by Leptospira interrogans serovar icterohaemorrhagiae/copenhagi. A decreased EOF was observed, suggesting a modification of erythrocyte components secondary to disturbances that occur during canine leptospirosis, such as renal damage and hepatic disease. PMID- 7997769 TI - [Parasitologic and serological evaluation of caprines experimentally inoculated with Trypanosoma cruzi]. AB - The experimental infection by Trypanosoma cruzi was studied in nine young goats. These animals were inoculated by intraperitoneal route with 10(3) trypomastigotes/Kg body weight with strains 147 (Group 1) and 229 (Group 2), isolated from chronic Chagasic patients proceeding from Bambui, Minas Gerais, Brazil. The infected animals were submitted to fresh blood examinations, xenodiagnosis, hemoculture and serology (IFAT and ELISA). The follow up of T. cruzi infection ranged from 7 to 30 months and it was possible to note a markable difference concerning the course of infection between the two groups. The parasite was visualized, for the first time in experimentally infected goats in the acute period through fresh blood examinations and xenodiagnosis and through hemoculture and xenodiagnosis during the chronic period of the Chagasic infection. These results suggest that, under some epidemiological conditions, goats may be important in the sylvatic and peridomiciliar transmission cycles of T. cruzi specially young animals. PMID- 7997770 TI - [Neurocysticercosis with initial clinical picture of acute meningitis]. AB - Twenty seven cases of neurocysticercosis, with clinical picture of acute meningitis, are described. Twenty (74.1%) patients are male; the age was 4 to 42 years (23.6 +/- 11.7 years). The etiologic diagnosis was defined by the complement fixation test (Weinberg) and/or enzyme-linked immunosorbent assay (ELISA) for cysticercosis in the cerebrospinal fluid (c. s. f.). Six patients that realized cranial computerized tomographic scan resembling neurocysticercosis. Twenty one (77.8%) have predominance of lymphomononuclear cells in the c. s. f. obtained in the admission to the hospital; in 6 (22.2%) there were predominance of polymorphonuclear neutrophils. In this c. s. f. lymphomononuclear pleocytosis and in three that have c. s. f. neutrophil pleocytosis, suggesting the diagnosis of neurocysticercosis. The treatment of acute neurocysticercosis was made with dexamethasone. All the patients survived and were transferred to the ambulatory of Neurology for follow-up and complementary treatment. PMID- 7997775 TI - [Contact dermatitis by pederine: clinical and epidemiological study in Ceara State, Brazil]. AB - Clinical and epidemiological aspects of the contact dermatitis by Paederus are studied. This zoodermatosis is observed in many countries of the Ceara, State of Brasil, during the rainy season, specially at the months of april and may. The etiological agent of this disease is an insect of the generus Paederus. Two species were identified in the State: Paederus brasiliensis and Paederus columbinus. PMID- 7997771 TI - Blood groups and malaria. AB - The possible relationship between erythrocyte antigens and the presence of malaria infection by P. vivax and P. falciparum was sought in four different ethnic groups of two departments of Colombia. Malaria infection by P. falciparum was found in 91.4% of malaria infected blacks. No significant differences were found between the presence of malaria infection and ABO antigens. In the other blood groups, it was observed that groups MNSs conferred black people a greater Rr for malaria by both species of Plasmodium and that Duffy-negative blacks and indians appeared to be resistant to P. vivax infection. A predominance of P. vivax infection was observed in Katio Indians while P. falciparum was predominant in Kuna Indians; the reason for this finding still needs to be explored. PMID- 7997773 TI - [Colonization of artificial ecotopes by Panstrongylus megistus in Santa Catarina Island, Florianopolis, Santa Catarina, Brazil]. AB - The aim of this work was to verify the colonization of Panstrongylus megistus on artificial ecotopes in Florianopolis, in the Santa Catarina Island, South Brazil. For this purpose 443 houses of the Lagoa district and 779 house annexes (524 chicken-houses, 46 corrals and 209 storage-houses) in 9 different places were examined from 1985 to 1992. These ecotopes, which include ceilings and basements, were checked after application of dislodging liquid (Pirisa 5%). Colonization by P. megistus was verified in two houses, three chicken-houses and one storage house of the Lagoa district, where eggs, nymphs and adults were collected. To verify local reports of P. megistus occurrence, another two houses and one school were investigated. The colonization at all of these places was confirmed. In the 9 artificial ecotopes examined, 559 eggs, 305 nymphs and 24 adults were collected. The infection rate of P. megistus by Trypanosoma cruzi was 55.3% (182/329). A similar infection rate of 56.5% (78/138) was obtained in adults of P. megistus from sylvatic ecotopes and in adults captured in the houses by the inhabitants between 1983 to 1991. Precipitin tests revealed blood from just one source in 94.0% of the insects (170/181). Human blood was found in 80.6% (25/31) of the adults and in 5.8% (1/17) of the nymphs captured in the houses. These results suggest the need to ally serious epidemiologic vigilance to the effort of the inhabitants in order to avoid the risk of domiciliation of P. megistus in the houses. PMID- 7997772 TI - [Presence of Toxocara spp eggs in public squares of Uberlandia city, Minas Gerais, Brazil]. AB - The objective of this study was to verify the presence of Toxocara spp eggs in the public squares ground in Uberlandia, region of Triangulo Mineiro, from October 1991 to January 1992. The city has 89 squares distributed in 39 boroughs. In order to have an outline of the parasite's occurrence, ground and sand (when existent) samples were collected from one square per boroughors. The squares were determined by draw. The homogenized ground samples of distinct points of the 39 squares, were collected in plastic flasks and analysed by the methods of fluctuation in sodium chloride saturated solution and magnesium sulphate saturated solution which contained 5% of potassium iodate. Both methods were executed twice for each sample. The results showed that the ground of 9 squares (23.07%) was contaminated, 6 of which were located near downtown. The execution of more than one laboratorial method permitted the agent's identification in a greater percentage of squares. PMID- 7997776 TI - Severe scorpion envenomation in Brazil. Clinical, laboratory and anatomopathological aspects. AB - Scorpion stings in Brazil are important not only because of their incidence but also for their potential ability to induce severe, and often fatal, clinical situations, especially among children. In this report we present the clinical and laboratory data of 4 patients victims of scorpion stings by T. serrulatus, who developed heart failure and pulmonary edema, with 3 of them dying within 24 hours of the sting. Anatomopathologic study of these patients revealed diffuse areas of myocardiocytolysis in addition to pulmonary edema. The surviving child presented enzymatic, electrocardiographic and echocardiographic changes compatible with severe cardiac involvement, which were reversed within 5 days. These findings reinforce the need for continuous monitoring of patients with severe scorpion envenoming during the hours immediately following the sting. PMID- 7997777 TI - Salmonella serovars in food poisoning episodes recorded in Brazil from 1982 to 1991. AB - The Salmonella serovars involved in 25 food poisoning episodes which occurred in the Southeast and South of Brazil from 1982 to 1991 were identified. The most frequently detected serotype was S. Typhimurium (13/25, 52%), and the food most frequently involved in the transmission of Salmonella was homemade mayonnaise. The need to set up a permanent program of epidemiologic alert for food poisoning is emphasized. PMID- 7997778 TI - [Inefficacy of bothropic antivenin in the neutralization of the coagulation activity of Lachesis muta muta venom. Report of a case and experimental confirmation]. AB - In the State of Amazonas and in areas nearby Manaus, the snakes responsible for the majority of accidents are Bothrops atrox and Lachesis muta muta, with a percentage of confirmed species of 76% and 17%, respectively. Frequently, in the absence of the laquetic and bothropic-laquetic antivenoms, the Instituto de Medicina Tropical de Manaus (IMTM) has been using bothropic antivenom in the treatment of laquetic accident. In this paper is related a case of accident caused by L. muta muta; the patient was treated with bothropic antivenom, and after received twenty ampoules of this antivenom, maintained blood incoagulability until the 13th day after the accident. Experiments to obtain the potency of the bothropic antivenom for the coagulant and hemorrhagic activities has been done, using Bothrops atrox venom as control. The results showed that the potency of the antivenom for the hemorrhagic activity was similar, and the potency for the coagulant activity for the L. m. muta venom was 9.2 times minor than that for B. atrox. The antibodies titles from three different lots of bothropic antivenom varied for the L. m. muta venom, and were constant for the B. atrox venom. Due to the inefficiency of the bothropic antivenom on the neutralization of the coagulant activity for the L. m. muta venom, the use of bothropic antivenom is not recommended in the treatment of Lachesis muta muta accidents. PMID- 7997779 TI - [Relationship of histoplasmin intradermal tests and antibodies levels detected by ELISA and immunodiffusion]. AB - A prospective study was carried out in two groups of individuals: a group 1 (n = 40) included workers from a poultry farm, with potential occupational risk of exposure to Histoplasma capsulatum, etiologic agent of histoplasmosis, and a group 2 (n = 16), persons without occupational risk of exposure to the agent. Histoplasmin skin test was performed in both groups, and three sera were obtained from each individual: 1) before skin test was done, 2) 30 days after, and 3) 180 days after it. In both groups the histoplasmin skin test, even when the test was positive, was not a sufficient antigenic booster to provoke an increase in the H. capsulatum antibody levels capable to be detected by the serologic tests used (ELISA and Double Immunodiffusion). These results contribute to improve the interpretation of ELISA test values in the diagnosis of histoplasmosis. PMID- 7997774 TI - Acute respiratory infections in children from a deprived urban population from Uruguay. AB - To obtain base line data on incidence, duration, clinical characteristics and etiology of acute respiratory infections (ARI), 276 children from deprived families living in Montevideo were followed during 32 months. The target population was divided into two groups for the analysis of the results: children aged less than 12 months and those older than this age. During the follow-up period 1.056 ARI episodes were recorded. ARI incidence was 5.2 per child/year. It was 87% higher in infants than in the older group, as was the duration of the episodes. Most of the diseases were mild. Tachypnea and retractions were seldom observed, but 12 children were referred to the hospital, and 2 infants died. Viral etiology was identified in 15.3% of the episodes. RSV was the predominant agent producing annual outbreaks. Moderate to heavy colonization of the upper respiratory tract by Streptococcus pneumoniae (32.3%) and Hemophilus sp. (18.9%) was recorded during ARI episodes. This community-based study furnish original data on ARI in Uruguay. It enabled to assess the impact of these infections on childhood. PMID- 7997781 TI - On leishmanial antigen detection in tissue sections of Montenegro's reaction. PMID- 7997780 TI - Schistosoma mansoni: the effect of dexamethasone on the cercaria-schistosomulum transformation, in vivo. AB - Treatment with dexamethasone (DMS) in the early phases of the experimental Schistosoma mansoni infection causes an indirect effect on the cercaria schistosomulum transformation process. This is observed when naive albino mice are treated with that drug (50 mg/Kg, subcutaneously) and infected intraperitoneally 01 hour later with about 500 S. mansoni cercariae (LE strain). An inhibition in the host cell adhesion to the larvae, with a simultaneous delay in the cercaria-schistosomulum transformation, is observed. This effect is probably due to a blockade of the neutrophil migration to the peritoneal cavity of mice, by an impairment of the release of chemotactic substances. Such delay probably favors the killing of S. mansoni larvae, still in the transformation process, by the vertebrate host defenses, as the complement system. PMID- 7997782 TI - [Homage to Raymundo Martins Castro: 1927-1993]. PMID- 7997784 TI - Is rhabdomyolysis an additional factor in the pathogenesis of acute renal failure in leptospirosis? AB - Leptospirosis is an important cause of acute renal failure in our environment. Although several mechanisms are implicated, the role of rhabdomyolysis in the pathogenesis of acute renal failure in leptospirosis has not been analysed. Sixteen patients with the diagnosis of leptospiroses consecutively admitted to the hospital were prospectively studied. The disease was characterized by sudden onset in all patients and, at admission, jaundice, conjunctival suffusion and myalgias. Mild to moderate proteinuria with unremarkable urinary sediment was recorded in 37.5% of the patients and abnormal levels of urea creatinine were found in 87.5% and 74.0%, respectively. Increased levels of aminotranspherase were documented in all 12 and CPK in all 10 patients studied. Serum myoglobin levels greater than 120 micrograms/l recorded in 56.2%. A correlation between myoglobin and renal failure or severity of disease, however, could not be established. PMID- 7997785 TI - [Human dermatomycoses in the interior of Rio Grande do Sul in the period of 1988 1992]. AB - The relative frequency of the dermatophytes in the central region of Rio Grande do Sul, Brazil, have changed during a survey carried out from 1988-1992. The frequency of the antropophilic species T. rubrum, T. mentagrophytes var. interdigitale and E. floccosum have decreased in comparison with the zoophilic species M. canis and T. mentagrophytes var. mentagrophytes. The relationship host/parasite and the low rate growth of dermatophytes in culture are discussed. PMID- 7997783 TI - [Isolation of Haemophilus aegyptius associated with Brazilian purpuric fever, of Chloropidae (Diptera) of the genera Hippelates and Liohippelates]. AB - The recognition of the Brazilian purpuric fever (BPF) in 1984 led to a number of studies which showed a relation between this disease and conjunctivitis caused by Haemophilus aegyptius. The increase in cases of conjunctivitis in children associated with higher population density of eye gnats (Chloropidae: Hippelates) has been reported since last century. This phenomenon is related to the attraction that those flies show for the eyes, secretions and wounds, from where they feed on. Although there are evidences on the role of these flies in the mechanical transmission of seasonal bacterial conjunctivitis, the isolation of Haemophilus aegyptius from them in their natural habitat had not been demonstrated yet. In this study Haemophilus aegyptius associated to BPF was isolated from two pools of chloropids collected around the eyes of children with conjunctivitis which were identified as Liohippelates peruanus (Becker) and a new species Hippelates neoproboscideus. PMID- 7997786 TI - Trichosporon beigelii peritonitis associated with continuous ambulatory peritoneal dialysis. AB - This paper reports a case of peritonitis caused by Trichosporon beigelii in a woman submitted to continuous ambulatory peritoneal dialysis. Diagnosis was established by direct examination and culture of dialysis effluent. PMID- 7997789 TI - Measles serodiagnosis: standardization and evaluation of a Dot-ELISA. AB - A Dot-ELISA using a measles virus (MV) antigen obtained by sodium deoxycholate treatment was standardized and evaluated for IgM and IgG antibody detection in measles patients and measles-vaccinated subjects. A total of 192 serum samples were studied, comprising 47 from patients with acute and convalescent measles, 55 from 9-month old children prior to measles vaccination and 41 from children of the same age after vaccination, and 49 from patients with unrelated diseases. The diagnostic performances of the IgG Dot-ELISA and IgG immunofluorescence test (IFT) were found to be close, varying from 0.97 to 1.00 in sensitivity and the specificities were maximum (1.00). Nevertheless, the sensitivity of the IgM Dot ELISA (0.85) was higher than that (0.63) of the IgM IFT, although both assays had comparably high (1.00) specificities. The IgM Dot-ELISA in particular proved to be more sensitive in relation to other assays studied by revealing antibodies in 80.0% (12/15) of vaccinated children on the 15th day after immunization. In contrast, the IgM IFT, failed to detect antibodies in the same group of vaccinated children. The stability of the MV antigen was longer than that of the IFT antigen, and the reproducibility of the Dot-Elisa was satisfactory. PMID- 7997787 TI - [Association of yeasts of the Cryptococcus genus with Eucalyptus species in Santafe de Bogota]. AB - Environmental isolation of Cryptococcus neoformans var. gattii was first made in Australia in 1989 by ELLIS. He established a specific association with the tree species Eucalyptus camaldulensis and E. tereticornis. Based on his findings, ELLIS proposed that the fungus could be exported from Australia to others regions, including Colombia, by means of infected seeds. The purpose of this study was to isolate and identify Cryptococcus sp., associated with Eucalyptus trees; this is the first ecological evaluation of C. neoformans var. gattii in our country. A total of 100 Eucalyptus trees, distributed among 13 zones, located in the center, northeast, east and west of Santafe de Bogota, were studied. Flowers, fruits, leaves, barks and Eucalyptus debris were collected. The samples were processed by extraction with saline solution containing antibiotics, cultured in selective media and the isolates were identified by morphological and biochemical characteristics. Twenty-seven isolates of 9 Cryptococcus sp. were recovered from 21 Eucalyptus trees, from 5 zones. One C. neoformans var. neoformans serotype A was recovered. The Cryptococcus associated with Eucalyptus is important because this is the first study done in our country. PMID- 7997788 TI - [Ultramicro ELISA to the detection of IgM antibodies in Mycobacterium leprae using dry blood samples]. AB - In this work the adequate conditions for the detection of IgM antibodies to PGL-I in eluates from dried blood spots using the UMELISA HANSEN and the SUMA technology are established. A total of 300 blood donors and 58 leprosy patients samples were studied. For both populations, in the previously established conditions, we compared the results of the eluates from dried blood spots with the serum samples, and was obtained a correlation of 0.919 in blood donors, 0.969 in patients, and 0.954 for the total of both populations. It was also obtained a level of agreement of 98% in patients and 96% in blood donors. In the patients population was found a sensitivity of 93% and an specificity of 100% for the eluates of dried blood spots evaluated by the UMELISA HANSEN in the comparison with the serum samples analized by the same assay. PMID- 7997791 TI - [Evaluation of a technique of sedimentation in tubes]. AB - The efficiency of sedimentation in test tubes for the detection of eggs of Ancylostomidae, Trichuris trichiura and Ascaris lumbricoides was tested in 80 mm high columns of fecal suspensions. Dilutions of 2.0%, 1.5% and 1.0% were tested by using samples containing, respectively, 12.5, 25.0, 50.0, 100.0, 150.0 and 200.0 eggs per gram (epg) of each helminth under study. Efficiency was evaluated in terms of frequency of positive results and eggs per slide of the sediment (0.078 ml). Both the frequencies of positive results and egg counts per slide increased with epg values, but were not apparently dependent from suspension dilutions within the range assessed. Sediments of 1.0% fecal suspensions were positive in 80.0% or more of the cases for epg values of 150.0. It is inferred that dilution values are not critical. Thus, it is not necessary to determine fecal weights or volumes instrumentally. Considering overall results, it may be concluded that 1.0% fecal dilutions should be recommended for best results both in terms transparency of the preparations and chances of recovering eggs, particularly when egg counts are low. PMID- 7997790 TI - Search of intravascular hemolysis in patients with the cutaneous form of loxoscelism. AB - Haptoglobin assay, a highly sensitive method to detect intravascular hemolysis was carried out in the sera of 19 patients referred to Hospital Vital Brazil with the cutaneous form of loxoscelism in order to investigate the occurrence of mild intravascular hemolysis. Data from this series did not show decreased levels haptoglobin, ruling out intravascular hemolysis in these patients with cutaneous form of loxoscelism. PMID- 7997792 TI - Evaluation of different methods for Plasmodia detection, in well defined population groups in an endemic area of Brazil (1). AB - In Brazil, more than 500,000 new cases of malaria were notified in 1992. Plasmodium falciparum and P. vivax are the responsible species for 99.3% of the cases. For adequate treatment, precoce diagnosis is necessary. In this work, we present the results of the traditional Plasmodia detection method, thick blood film (TBF), and the results of alternative methods: Immunofluorescence assay (IFA) with polyclonal antibody and Quantitative Buffy Coat method (QBC) in a well defined population groups. The analysis were done in relation to the presence or absence of malaria clinical symptoms. Also different classes of immunoglobulins anti-P.falciparum were quantified for the global analysis of the results, mainly in the discrepant results. We concluded that alternative methods are more sensitive than TBF and that the association of epidemiological, clinical and laboratory findings is necessary to define the presence of malaria. PMID- 7997794 TI - [Disseminated histoplasmosis in patients with acquired immunodeficiency syndrome (AIDS). Study of 25 cases]. AB - Twenty five cases of disseminated histoplasmosis in patients with AIDS are presented. Mucocutaneous involvement established the diagnosis of disseminated histoplasmosis in 68% of the cases. We point out the importance of histoplasmosis as an opportunistic infection in patients with HIV. PMID- 7997795 TI - [Nasofacial zygomycosis. Report of a case of Para state, Brazil]. AB - A case of nasofacial zygomycosis in a 64-year-old female patient from Barcarena, State of Para, is reported. This is the second time that the disease is recognized in Northern Brazil. The diagnosis was initially suspected by the direct observation of broad coenocytic hyphae in biopsy specimens of the nasal cavity mucosa. Later, the cause of the disease was confirmed by the mycologial and histopathological findings. Rapid response to the therapy with potassium iodide was achieved, without however a complete resolution of the lesions. The patient still remains under treatment, with itraconazole and iodide. PMID- 7997793 TI - Alkaline soluble Trypanosoma cruzi epimastigote antigen (ASEA) applied to Dot ELISA. AB - The alkaline soluble Trypanosoma cruzi epimastigote antigen (ASEA) was assessed in dot-ELISA for the diagnosis of Chagas' disease. Serum samples (355) from chagasic and non-chagasic patients were studied, and IgG antibodies to ASEA were found in all patients with chronic Chagas' disease. In non-chagasic patients 95.6% were negative, except for those with leishmaniasis (visceral and mucocutaneous), and some patients from control group reacted in low titers. The data indicate that dot-ELISA using ASEA is suitable for seroepidemiologic surveys to be employed in endemic areas for Chagas' disease. PMID- 7997796 TI - [Subcutaneous phaeohyphomycose due to Exophiala jeanselmir. Report of 3 cases in patients with a kidney transplant]. AB - We report three cases of subcutaneous phaeohyphomycosis due to Exophiala jeanselmei (Langeron) McGinnis et Padhye 1977, in kidney transplant patients. Exophiala jeanselmei is a dematious fungus having also ability to rarely procedure eumycetoma (black grains). According to KWON-CHUNG & BENNETT (1992) such fungus is antigenically very heterogeneous, since so far three serotypes have been identified; each serotype including subgroups. Subcutaneous phaeohyphomycosis is becoming more and more frequent in kidney transplant patients submitted to an immunosuppressive treatment. As Exophiala jeanselmei has already been isolated from the environment it becomes difficult to explain the pathogenicity of these cases by a reactivation of quiescent processes. The authors suggest an occasional fungistatic action of cyclosporine A upon Exophiala jeanselmei. PMID- 7997797 TI - Granulomatous inflammation. PMID- 7997799 TI - Marketing strategies that will work for your laboratory ... regardless of size. PMID- 7997800 TI - A simple path to a complex crown. PMID- 7997798 TI - Oogram studies in mice infected with Schistosoma mansoni and treated with dexamethasone. AB - Mice infected with about 90 cercariae of Schistosoma mansoni (LE strain) were treated during five consecutive days with dexamethasone (50 mg/Kg, subcutaneously), starting on the 42nd day of infection. Groups of five mice were then daily sacrificed from the first day after onset of treatment until the first day after. The perfusion of the portal system was performed and a piece of the intestine was processed for qualitative and quantitative oograms. This treatment carries to larger numbers of eggs in the tissues of treated mice, when compared with untreated groups. No changes were observed in the kinetics of oviposition, as all stages of viable eggs were observed in the tissues of treated and control mice. These data reinforce the hypothesis of a partial blockade of the egg excretion in immunosuppressed mice. PMID- 7997801 TI - A technique for developing a master cast with previously made dies. AB - This article describes a technique for preparing final working casts to be used in the laboratory phase of restorative treatment. The goal is to produce accurate working casts that have stable dies which are easily removed from the base and reliably replaced. Most casts with removable dies are made from a single master impression. However, individual dies are sometimes made previously from individual tooth (preparation) impressions. In such cases, transfer copings are required to relate the dies and produce the final working cast. Hollow plastic casting sprues are used as temporary dowels in this technique until a transfer coping pickup impression has been made. After the dies are seated and secured in the transfer coping pickup impression, the plastic casting sprues are replaced with conventional brass dowel pins. This technique ensures well-placed dowel pins that will facilitate easy and accurate withdrawal and replacement of the dies. PMID- 7997802 TI - Tissue differences in the expression of mRNAs of Ha-ras, c-myc, fos and jun in human uterine endometrium, myometrium and leiomyoma under the influence of estrogen/progesterone. AB - Ha-ras expression level in uterine endometrium (EM) in the proliferative phase (PP) was significantly higher than that in the secretory phase (SP). c-myc expressions were detected in EM, uterine myometrium (MM) and uterine leiomyoma (LM) without any cyclic change; fos expressions in LM, MM, and EM were detectable in PP, but not in SP. jun expression level in LM was significantly higher than that in MM and EM in PP, but did not alter during the menstrual cycle. Estrogen elevated the levels of Ha-ras and fos mRNAs in the three tissues, jun mRNA in MM and EM, and c-myc mRNA in LM and MM. These results suggest that there is a tissue difference in the expression of Ha-ras, c-myc, fos and jun among EM, MM and LM, under the influence of estrogen/progesterone. PMID- 7997803 TI - Study of a new tumor marker, CYFRA 21-1, in malignant and nonmalignant diseases. AB - The diagnostic value of a new tumor marker, CYFRA 21-1, was studied in the sera of 50 controls, 206 patients with benign diseases and 469 patients with malignancies. Fifty controls showed mean serum concentrations of 1.2 +/- 0.5 ng/ml. Using 3.3 ng/ml as the cutoff, abnormal CYFRA levels were found in 13.1% of patients with benign diseases, mainly in those with liver cirrhosis (29.4%) or renal failure (20.8%), and in 44.4% (180/405) of patients with active cancer. Neither healthy subjects nor no evidence of disease (64 cases) patients had serum levels higher than this limit. CYFRA 21-1 results were significantly higher in patients with active cancer than in those with benign diseases or without active tumors (p < 0.0001). CYFRA serum levels were significantly higher in patients with metastases (59.5%) than in those with locoregional disease (33.7%; p < 0.001). CYFRA 21-1 sensitivity in patients with lung cancer was related to tumor histology with abnormal levels in 65.6% of patients with non-small cell lung cancer and in 25% of patients with small cell lung cancer (p < 0.0001). In breast cancer, CYFRA 21-1 concentrations were significantly higher in patients with metastases and in patients with primary tumors but with nodal involvement (p < 0.001). PMID- 7997806 TI - Cell loss in dimethylbenz(a)anthracene-induced rat mammary carcinoma treated with toremifene and ovariectomy. AB - The antiestrogen toremifene treatment results in regression or stabilization of dimethylbenz(a)anthracene(DMBA)-induced rat mammary tumors by reducing the mitotic activity and possibly by modifying the abundant spontaneous apoptosis seen in these tumors. A comparative study on the modes of cell loss was performed in untreated DMBA tumors and in tumors treated with toremifene and ovariectomy. Ovariectomy results in massive apoptotic cell death throughout the tumors with apoptotic cells exfoliating into the glandular lumina. Apoptosis accounts for most of the cell death also in the untreated tumors. The distinctly different morphology of the apoptotic cells in the untreated tumors (condensed apoptosis) and tumors treated with ovariectomy (blebbing apoptosis) may reflect the different type or schedule of the apoptotic process. Both morphologies of apoptotic cells were seen in the toremifene-treated tumors. Blebbing apoptosis is not easily examined in paraffin-embedded material but is best detectable in plastic sections and by electron microscopy. PMID- 7997804 TI - In vivo modulation of human tumor cell growth by normal human extracellular matrix. AB - The extracellular matrix (ECM) is actively involved in the growth and maintenance of normal and neoplastic mammalian cells. It has been suggested that the growth promoting factors sequestered within the matrix exclusively regulate the observed phenomena. We postulate, however, that ECM components alone, when derived from normal human tissues, and devoid of major growth factors, can modulate the growth of human tumor cells in vivo. In this submission we provide evidence that Amgel, an ECM created by us from nontumorigenic human placental tissues, can enhance or retard human cell growth in vivo, depending upon type, when placed in the subcutaneous tissue of athymic mice. Further, we provide evidence that these results differ from those obtained utilizing a tumor-derived ECM. Our findings suggest that specific tumor cell-matrix interactions are responsible for the observed results. To the best of our knowledge, this is the first report of a normal, human tissue-derived ECM both promoting and inhibiting selected human tumor cell growth in vivo. Thus, Amgel should prove useful in elucidating the underlying mechanisms of cell-matrix interactions during the growth and progression of human neoplasms. PMID- 7997805 TI - Serum markers CASA and CA 15-3 in ovarian cancer: all MUC1 assays are not the same. AB - The serum MUC1 markers CASA and CA 15-3 were compared with CA 125 in the serum of patients with ovarian cancer and in pregnant women. Used individually, CASA and CA 15-3 gave sensitivities of 54 and 56% in pre-operative ovarian carcinoma (n = 50), though these were lower than with CA 125 (84%). CASA levels were elevated in 3 women with a negative CA 125, while CA 15-3 was elevated in 2 of these women. The combined use of CA 125 with CASA or CA 15-3 led to the preclinical detection of recurrence in 4/5 patients, with mean lead times of 3.6 and 4.3 months, respectively. Of particular interest was the marked difference in reactivity observed with CASA and CA 15-3 in some patients, despite both assays utilising monoclonal antibodies (MAbs) that react with the MUC1 mucin. CA 15-3 and CASA showed a lower than expected correlation in patients with ovarian cancer (r = 0.70), with some patients having high concentrations of one mucin marker and low concentrations of another. Furthermore, different marker profiles were observed when monitoring the progress of patients with these markers. Marked differences between CA 15-3 and CASA were also observed in the serum of pregnant women (n = 10), where CASA showed marked elevation (mean 33.6 times cutpoint) and CA 15-3 did not (mean 0.88 times cutpoint). These data suggest that the specificities of the MAbs used in these assays affect the glycoform of MUC1 detected, and that it should not be assumed that all MUC1 assays will behave in the same manner. PMID- 7997808 TI - Tissue polypeptide-specific antigen and CA 125 as serum tumor markers in ovarian carcinoma. AB - The serum levels of tissue polypeptide-specific (TPS) antigen were measured using the M3 monoclonal antibody in an enzyme immunoassay in 33 patients with ovarian cancer, in 26 women with benign pelvic masses and in 26 women with a laparoscopically proven normal pelvis. The results were compared with the serum levels of the CA 125 antigen. At a cutoff level of 135 U/l for TPS and 20 U/l for CA 125 (95th percentile of the healthy controls), the sensitivity of the tests for detecting a malignant tumor was 77% for TPS and 87% for CA 125. The specificities were 85% for TPS and 92% for CA 125. Adding TPS to CA 125 did not increase the diagnostic values compared to using the CA 125 test alone. For both markers, the rate of positivity was higher in advanced stage than in early-stage ovarian cancer. No correlation between marker levels and survival was found. Serial determinations performed with 4 patients during therapy and follow-up showed that both TPS and CA 125 are good predictors of tumor response and recurrence. PMID- 7997807 TI - Action of nitrogenated and sulfonylated inositol derivatives upon the proliferation in vitro of normal mouse cells and tumor mouse cells. AB - Despite the major advances of cancer chemotherapy during the past 40 years, host toxicities and drug resistance justify the need to continue the search for new antineoplastic agents. In the present work, we have studied the effect of six synthetic drugs on the in vitro growth of two murine mammary adenocarcinomas (M3 and MM3), as well as on normal embryonic cells. AI, MIC and MPI are purines coupled to a sulfonylated inositol, while DIC and DEI have nitrogen mustard as substituent. Methylsulfonylmucoinositol was the common substituent. Our results indicated that only drugs substituted with nitrogen mustards had an antiproliferative effect. DEI was more effective on tumor cells than on normal cells. PMID- 7997809 TI - Evaluation of organophosphorus and synthetic pyrethroid insecticides against six vector mosquitoe species. AB - Three organophosphorus compounds- malathion, folithion and temephos- and two synthetic pyrethroids- alphamethrin and deltamethrin- were used for monitoring the susceptibility status of larvae and adults of six vector mosquito species: Culex quinquefasciatus (Filariasis) and Aedes albopictus (Dengue) (both laboratory and field strains); laboratory strains of Aedes aegypti (Dengue), Anopheles stephensi and Anopheles culicifacies (Malaria), and Culex tritaeniorhynchus (Japanese encephalitis) in India. From the LC50 values obtained for these insecticides, it was found that all mosquito species including the field strains of Cx. quinquefasciatus and Ae. albopictus were highly susceptible Except for Cx. quinquefasciatus (field strain) against malathion, 100% mortality was observed at the discriminating dosages recommended by World Health Organization. The residual effect of alphamethrin, deltamethrin, malathion and folithion at 25 mg (ai)/m2 on different surfaces against six species of vector mosquitoes showed that alphamethrin was the most effective on all four treated surfaces (mud, plywood, cement and thatch). Nevertheless, residual efficacy lasted longer on thatch than on the other surfaces. Therefore, synthetic pyrethroids such as alphamethrin can be effectively employed in integrated vector control operations. PMID- 7997810 TI - Studies on mosquitoes (Diptera: Culicidae) and anthropic environment. 4--Survey of resting adults and synanthropic behaviour in south-eastern, Brazil. AB - Resting adults Culicidae were collected from January 1992 through January 1993 in several habitats of the Ribeira Valley region. The diversity of species found among them suggested that the vegetation remaining within human settlements favored the survival and the population increase of some mosquitoes. Among there are: Ae. scapularis, Ae. serratus, Cx. (Culex), Cx. nigripalpus and Cx. (Melanoconion) such as Cx. ribeirensis. That preservation role may be attributed to the rearing of livestock and the consequent increase in the number of blood sources. These species may be classified as hemisynanthropes and Cx. oedipus apparently evolving to the eusynanthropic status. On the other hand, An. cruzii showed an asynanthropic behaviour, with a low degree of survival in the modified human environment. Epidemiological implications of the data are mentioned. PMID- 7997811 TI - [Relationship between the pathogenicity of Schistosoma mansoni in mice and the susceptibility of the mollusk vector. II. Number of eggs in feces and number and size of granuloma in visceras]. AB - The influence of the susceptibility of the vector snails of S. mansoni on the development of the pathogenicity of the worm to the host was studied. Off-spring of snails Biomphalaria glabrata and Biomphalaria tenagophila were used, selected with regard to the susceptibility to S. mansoni of the strains BH and SJ trait, respectively. Parenteral, F1, F2, F3 and F4 generation cercariae were used for the infection of Swiss mice, which were killed eight weeks after infection. The number of eggs in the feces and the number of granulomas in the liver, spleen and intestines were counted. The size of the granulomatous reactions was evaluated. The results led to the conclusion that greater susceptibility of B. tenagophila was associated with a larger egg production in the feces and a higher density of granulomas in the liver. There is a clear inverse relationship between the area of hepatic, splenic and intestinal granulomas and the rate of infection of the snails which served as intermediate hosts for the S. mansoni. PMID- 7997812 TI - [Immunologic and parasitologic aspects of Biomphalaria tenagophila infected by Schistosoma mansoni and other Digenea]. AB - The behavior of Biomphalaria tenagophila amoebocytes was studied in infections produced by Schistosoma mansoni and other Digenea. The resistance to superinfection was also verified in mixed infections. Data on amoebocyte phagocytic activity, on the number of amoebocytes in hemolymph, and on amoebocyte tissue reactions were obtained and electrophoretic and immunodiffusion examinations of the hemolymph were carried out. It was concluded that the snails infected with Digenea show resistance to superinfection with S. mansoni. Apparently sporocysts are not destroyed by the action of amoebocytes. An increase in amoebocyte phagocytic activity was discovered in infected snails. Immunoelectrophoresis shows quantitative and qualitative differences in the hemolymph of the infected snails. PMID- 7997813 TI - [Control of hemotherapy and transfusional Chagas disease: 1988 and 1990]. AB - An inquiry with the objective of bringing the study of the hemotherapy situation in the state of S. Paulo, up-to-date was undertaken in 1990 and compared with that carried out in 1988. In 1990 research was undertaken in 62 counties, 48 of which performed blood transfusions through 104 services, with hemocenter participation in 13.5% of these latter. In 1988 the respective figures were 57, 40, 71 and 8.5%. The number of donors and transfusions and prevalence of serological positivity for Chagas' disease were, respectively: 105,170; 79,544 and 1.24%, while in 1988 the corresponding numbers were: 51,614; 49,211 and 1.52%. Evaluating the serological selection it was found that the following percentages of the services performed serological tests: for Chagas' disease (94.2%), syphilis (94.2%), hepatitis (94.2%), HIV (92.3%) and malaria (20.2%) while in 1988 only 69.0%; 70.4%; 67.6%, 63.4% and 16.9%, respectively, of the services utilized these same tests. In respect of the serological trial specific for Chagas' disease the results were: complement fixation-4.9%; latex-4.0%; indirect immunofluoresce-80%; direct hemaglutination-24.0%, indirect hemaglutination-69.0% and ELISA-59.0% of all services. In the preceding inquiry only 14.3% of the services performed the ELISA test, and complement fixation was utilized in 28.6%. The results show that the services are utilizing ever more sensitive techniques in the serological routine. Further it was observed that in 1988, 77.6% of all the services studied used only one technique for the diagnosis of Chagas' disease while in 1990 92.9% utilized two or more different techniques. It is concluded that the quality of the hemotherapy undertaken in the state of S. Paulo has improved significantly. PMID- 7997814 TI - [Dental caries distribution in preschool children in an urban area of Argentina, 1992]. AB - An investigation undertaken into a sample of 1,115 five-year old children attending kindergartens in the city of Cordoba (Argentina) is described. The investigation aimed at establishing the prevalence and distribution of dental caries by socioeconomic level. Research showed that the prevalence of caries had decreased 55.0% in relation to the 1973 figure, while the proportion of children with healthy teeth was 26.7% greater. The frequency and seriousness of the caries increased as the child's social position declined. At the highest socioeconomic level NES I = entrepreneurial and managerial bourgeoisie), the rates of caries were significantly lower than those at the lowest socioeconomic level (NES III = typical proletariat, nontypical proletariat and sub-proletariat) presenting dmf-t of 0.8 and 2.7, and dmf-s of 0.9 and 4.9, respectively. In NES III, the dmf-t main components were decayed and missing teeth, while in NES I filled teeth were the main components. The proportion of children with no experience of caries was 63.1% in NES I and 11.5% in NES III. Inversly, the rate dental health was higher in NES I (8.8) than in NES III (5.1). The cost per child required for the restorative treatment in approximately two and a half times greater in NES III than in NES I. Considering the sample as a whole the expenditure required for NES III would be more than ten times higher than that required for NES I.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7997815 TI - [Probability of dying in the first year of life in an urban area of southern Brazil]. AB - A birth-cohort of 4,876 children born alive in hospital were selected and followed through up to the age of one year with a view to estimating the risk of dying in the first year of life. All of them were born in 1989, in one of the seven hospitals of an urban area of Southern Brazil and the only requirement for belonging to the cohort was that of residence on the area. The selected variables were: sex, birthweight, age at moment of death, underlying cause of death, and maternal age. The estimated probability of dying in the first year was of 19.9 per 1,000 (77.3% of the deaths occurred during the neonatal period). Perinatal causes and congenital malformations contributed to 80% of the deaths, and infectious diseases were the underlying cause of death in only 1.1% of the losses. The risk of dying in the first year of life due to afections arising during the perinatal period was higher among vaginally delivered babies (20.3 per 1,000) than it was for those born by cesarean section (9 per 1,000). A higher probability of death was present among infants born to adolescent mothers, and those with low birthweight (less than 2,500g). The results brought out the need for improving the quality of prenatal and infant care. They also suggested the hypothesis of a possible association between higher infant mortality and lower socio-economic level. PMID- 7997816 TI - Nutritional factors in milk from Brazilian mothers delivering small for gestational age neonates. AB - The composition of breast milk from brazilian mothers delivering low birthweight infants and its adequacy as a source of nutrients for this group has not yet been fully elucidated. A total of 209 milk samples from 66 women were analysed. The mothers were divided into three groups: G1, mothers delivering term babies of low birthweight (TSGA, n = 16); G2, mothers delivering preterm babies of appropriate birthweight (PTAGA, n = 20); G3, mothers delivering term babies of appropriate birthweight (TAGA, n = 30). The following factors were analysed: osmolarity, total proteins and protein fractions, creamatocrit, sodium, potassium, calcium and magnesium. Milk samples were collected 48 h and 7, 15, 30 and 60 days after delivery. The groups did not differ significantly in terms of osmolarity, total proteins and fractions, creamatocrit, calcium, magnesium or potassium throughout the study period. Sodium levels were higher in all samples from mothers of TSGA infants and in samples from mothers of PTAGA infants on the 7th, 15th and 30th days than in milk from the TAGA group. The authors consider the needs of the low birthweight and TAGA infants and that these high sodium levels may be necessary for growth of low birthweight infants. PMID- 7997817 TI - [Process assessment in the care for patients with chronic degenerative disease in a basic health unit]. AB - The efficacy of health actions, related to arterial hypertension and used as a strategy to decrease morbimortality due to cardiovascular diseases, in accordance with the "risk approach" and carried out in a Primary Health Care Clinic is assessed. These actions are based on the detection of arterial hypertension in the adult population attended at the Clinic and on the control of blood pressure levels in hypertensive individuals in which other known risk factors continue to be controlled, as well as on further treatment of eventual complications. Data relating to the 3,793 patients who were attended at least once by doctors of the adult sector of a training health-center located in S. Paulo county (Brazil) during the period from June 1990 to May 1991, inclusive, were evaluated. This evaluation was made according to each diagnosis undertaken as well as to the concentration of each type of consultation whether occasional, or follow-up. Of these 3,793 patients analysed, 839 presented arterial hypertension and/or diabetes, and were grouped into four categories: the exclusively hypertensive, the hypertensive with other associated chronic diseases (except diabetes), the diabetic and the diabetic with arterial hypertension. The results of this study brought the following aspects to light: 1) The low coverage of hypertensive individuals and diabetics being attended by the health service when only the population attended by the health service is taken into consideration. 2) The incidence of patients diagnosed as hypertensive in occasional consultations who did not return to the health service for medical follow-up indicates the difficulties involved in attracting such individuals permanently.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7997818 TI - [The female place in construction of adolescence concept]. AB - The origins of the concept of adolescence are discussed with a view to explaining certain of its critical aspects such as the predominance of bio-naturist though and notional androcentrism in its development. The discussion of this theme seeks also to contribute to a more adequate assistance to adolescents as well as to on enlargement of the concept of adolescence as related to the field of Public Health. PMID- 7997819 TI - [Nutritional status of children under 5 years of age in indian villages of the Parakana tribe in Brazil's eastern Amazonia]. AB - The evolution of the nutritional status of children under 5 years of age living in two Indian settlements of the Parakana tribe, Maroxewara and Paratininga, situated in the southeast of Para State (Brazil), with less than 20 years of direct contact with our society, was studied. The main purpose of this study was to register the effects of the preventive and curative health activities of the "Parakana Program" (created by an agreement between the National Indian Foundation- FUNAI and Northern Hydroelectric Project- ELETRONORTE), undertaken with the technical cooperation of the Tropical Medicine Center (Federal University of Para). Anthropometric data were obtained in there cross-sectional studies (April 89; January 90 and October 91) for the purpose of evaluating the prevalence of malnutrition by means of Gomez's, Waterlow's and WHO criteria. The evolution of nutritional status was evaluated in the light of the rate of growth and accepting weight increments superior to those expected among well-nourished children as a goal. Seventy children (87.5% of all the 0-5 years-olds living there) were followed through throughout the studies. Prevalence of malnutrition was greater in Paranatinga than in Maroxewara, possibly because the former was more populous and had had longer inter-racial contact. Paranatinga's anthropometric indices (wt/age, ht/age and wt/ht) were the lower. Most of the severe forms of malnutrition were found there too. Children between six months and 2 years old were the most affected.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7997821 TI - [Prevalence of organic brain syndrome in an elderly population in an metropolitan area of the southeastern region of Brazil]. AB - This paper is a summary of the main findings concerning organic brain syndrome (O.S.S.) in a prevalence study carried out among the elderly population of the city of Rio de Janeiro, Brazil. The project selected three districts of the city Copacabana, Meier and Santa Cruz-in view of a set of indicators. The study for the validation and reliability of the diagnostic instrument was carried out in the district of Copacabana. Prevalence results for organic brain syndrome were 5.9% in Copacabana, 9.84% in Meier and 29.75% in Santa Cruz. Several hypotheses have been formulated in the attempt to explain such diverse results within a single city. Associations with a variety of socio-economic indicators are presented. Dependence and loss of autonomy in elderly people are closely associated with organic brain syndrome. The results are compared with national and international findings. PMID- 7997820 TI - [Validation of the three color CIMDER band as an instrument for the detection of nutritional risk in preschool children]. AB - The value of the use, by the health agents in Rondonia, Brazil, of the nutritional classification proposed by the Multidisciplinary Research Center for Rural Development (CIMDER), Colombia, known as the three color CIMDER band, is analyzed. The band, used to measure arm circumference, would be used as an instrument for the detection of nutritional risk in children under five years of age and for referring them to larger, more complex, health units. For this purpose, a sample of 1,268 children were studied. The results of the nutritional classification obtained by the band and the results of Gomez classification were compared. The application of the validations tests resulted in the following values: sensibility = 77.1%; specificity = 68.8%; positive predictive value = 59.0%; negative predictive value = 83.7%; rate of false positives = 31.2% and rate of false negatives = 22.9%. Except for the rate of false positives, the rest of the results were considered to be satisfactory, sufficiently so to recommend the use of the CIMDER band as an instrument of selection by the health agents in Rondonia. More specific indicators should be adopted at the larger, more complex health units, with a view to reducing the number of false positives in the programs for attendance to the undernourished. PMID- 7997822 TI - [Neonatal mortality in residents of an urban locality in the southern region of Brazil]. AB - Neonatal mortality rates in Maringa, Parana State, Brazil, in 1990 are characterized in terms of several variables. Information concerning these events was provided by death certificates, hospital archives, home interviews, health center files and necropsy records. Neonatal mortality rates were 19.4 per 1,000 live births. Most of the deaths occurred: the first week of life (92.0%); newborns with less than 37 weeks of gestation (79.8%); low birth weight infants (74.1%); male newborns (56.3%); and cesarean section births (54.2%). The underlying causes of death were codified in accordance with the "International Diseases Classification"-9th revision. Perinatal Causes together with Congenital Anomalies accounted for 94.0% of these deaths in addition also to being responsible for 83.2% of neonatal deaths; prematurity was considered the main cause, accounting for 15.8% of deaths while being the most frequent cause associated with newborn deaths (59.0%). PMID- 7997823 TI - [Health profile of children cared for in nurseries and the prevention of communication disorders]. AB - For the purpose of characterizing the health of the population assisted by the Nursery Program (Programa Creche) at the three units financed by the city authorities of S. Paulo, Brazil, an enquiry was undertaken. A questionnaire consisting of both open and closed question concerning personal identification, personal antecedents, development and health was prepared and 133 of them were applied. Results indicated that children whose living conditions were unsatisfactory (humid and overcrowded housing) have presented respiratory infections and otitis in greater numbers. Most of the children were breast-fed at first but started being nursed artificially when two months old. Salty and varied texture foods were introduced at the appropriate ages and well accepted. Language delay is related predominantly to ages 3 to 7. Parents act properly lin communication situations. It is considered that the systematic use of the questionnaire proposed will permit not only better knowledge of the health of the children, benefitting the multidisciplinary attendance and integration of the child, as also the improvement of preventive practices and make the surveillance of difficulties in communication possible. PMID- 7997825 TI - [Chagas' disease as main cause of death in the southeastern region of Brazil: presence of contributory causes]. AB - Death certificates of all persons who died in in the State of S.Paulo, Brazil and which presented Chagas' disease as the principal cause of death, were studied with a view to analysing the existing additional information available as to contributory causes. After a direct reading of the 1,308 death certificates, the contributory causes were identified and registered. They were mentioned in 261 (20%) of the certificates, 185 of them presenting only one, and 75 two of them. The 6 more frequent contributory causes were: "megas", embolism, chronic pulmonary disease, infections (other than Chagas' disease), arterial hypertension and malnutrition. When analysing the presence of the contributory causes in two groups-persons of less than 50 years old, and those older than 50 a higher proportion of them was observed in the older group and a distinct profile of causes was found for each group. No statistic association was observed between contributory causes and sex or site of residence. PMID- 7997824 TI - [Population interactions between Triatoma infestans and Triatoma sordida]. AB - Populations of T. infestans and T. sordida were studied between September 1988 and April 1989 with a view to discovering if any kind of interaction took place between them while they lives together in the same experimental unit and exploited the same food resource (chicken). The initial age structure for each species was: 27 N1, 7 N2, 11 N3, 3 N4, 8 N5, 4 males and 10 females. The population dynamics nutritional status, predation and gregarious behavior were estimated by means of a monthly census. The colonizing success of T. infestans was greater than that of T. sordida in view of the values obtained: fecundity (146 eggs/female), longevity (157.8 days) and mortality (39.4) compared with the values recorded for T. sordida: 118 eggs/female, 81.1 days and 54.0% respectively. The population growth of T. insfestans followed an exponential model, with a high nymphal recruitment rate, while the T. sordida population was early extinguished. In general, the average weight of T. infestans remained close to the initial values while that of T. sordida declined. Gregarious groups were formed principally in the inferior sector of wall 1 (near the host) with a higher aggregation in T. infestans. These results make it possible to propose the hypothesis of the competitive superiority of T. infestans. PMID- 7997826 TI - [Seroepidemiologic survey of leptospirosis among environmental sanitation workers in an urban locality in the southern region of Brazil]. AB - Sera from 386 environmental sanitation workers, concerned with water supply, drains and drainage galleries, sewers, garbage collection and road sweepers, were examined for leptospiral agglutinins by the microscopic agglutination test. Altogether 40 of the 386 workers (10.4%) were positive to one or more serovars; however, the difference in seropositivity between the professional categories was not significant (p < 0.05). Twelve serovars were recorded among the seropositive workers with predominance of L. castelonis and L. australis; but the difference between the serovars was not statistically significant (p > 0.05). Of the seropositive workers, 86.9% had agglutination titres > or = 100 and < or = 400; the rates for titres 100 and 400 were higher than 800, 1,600 and 3,200 (p < 0.05). PMID- 7997828 TI - [Advances in rabies research]. AB - Recent advances in research into rabies, based on the technological process of the biological sciences mainly molecular biology and genetic engineering, are mentioned. The current knowledge of the characteristics, properties pathogeny and immunology of the rabies views is presented, as well as the development of new diagnostic and vaccine evaluation techniques. The epidemiological importance of the identification of different immunogenic rabies virus strains and the role in immunoprophylaxis of the production of highly immunogenic vaccines, are set out. PMID- 7997827 TI - [Current characteristics associated with a history of induced abortion]. AB - For the purpose of analysing the association between selected current socio demographic characteristics and the history of induced abortion, 138 students of a Brazilian university, who had been pregnant at least once, were studied. These students were identified from among the 937 who returned, by mail, a self administered, anonymous questionnaire distributed to all the female undergraduates. The subjects were divided into two groups, those who had and those who did not have a history of induced abortion. It was found that the largest percentage of women who had already had an induced abortion were of less than 24 years of age, were not living in marital union, had no religious affiliation and no living children at the time of the study. Analysis by logistic regression showed that having no living children was the only current characteristic associated with having had an induced abortion. PMID- 7997829 TI - [Anthropometric and dietetic study of competitive swimmers from metropolitan areas of the southeastern region of Brazil]. AB - The daily food intake and alimentary frequency of competitive swimmers of two clubs representative of the two largest cities in Brazil (S. Paulo and Rio de Janeiro) were studied. The 30 males and 37 females studied belonged to the swimming categories "junior" (15-17 yrs old) and "senior" (18-25 yrs old). Food intake obtained from self-register and 24 hour-recall showed similar results and therefore the 24 hour-recall was used for comparisons with the literature. Ages within both sexes were anthropometrically similar. The most frequently eaten foodstaffs were similar to those quoted by the metropolitan population of the respective areas. Moreover, the athletes from both cities reported similar food supplements. The energy intake was found to average almost double the estimated value for the respective metropolitan populations, but were similar to results obtained for swimmers all over the world. Snacks between meals supplied 25-28% of the overall energy intake. The main caloric source were cereals. However, despite their contribution of almost 50% of the total energy intake, carbohydrates attained a level of only 55-60% of that recommended for competitive athletes. On the other hand, the protein intake found (2.5-3.0 g/kg/day) exceeded the recommended values by 100%. The fat intake particularly of satured fat, was also considered high. The swimmers' intake of micronutrients was well abone that quoted by the regular population of these metropolitan areas, when related to the caloric intake, but the values of Mg, Fe and vitamins A and D were somecohot lower than those recommended.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7997830 TI - Production of emotions by hearing-impaired and normal-hearing children. AB - The present study examined the ability of hearing-impaired (HI) individuals compared with normal-hearing (NH) individuals to transmit non-verbal information on emotions and investigated the acoustical characteristics of their expressions of different emotions. Seven HI and five NH children produced one sentence in five different emotions: anger, fear, happiness, sadness, and neutral. The productions were judged by three naive listeners. The results indicated that the NH children's emotional expressions were perceived more accurately than those of the HI children. The accurately perceived productions underwent acoustical analysis. The results indicated significant differences in the fundamental frequency (Fo) range and in the intensity of the NH and HI children's productions. There were no significant intergroup differences in the productions' mean Fo or in the total duration. It was also shown that the five emotions examined differed significantly in all of the measured acoustical parameters among both NH and HI children. PMID- 7997831 TI - Hearing aid measurements with speech and noise signals. AB - An increasing number of hearing aid types include one or more features which are intentionally non-linear. In such devices measurement of frequency response and distortion using sweep tone measurements are typically of little relevance. Five different non-linear hearing aid types were used to evaluate three different broad-band measuring methods. The results revealed that these methods were meaningful in estimating average frequency response obtained with a specific input signal, but none of the three methods used in the study was able to evaluate separately the effects of the most important signal modifications: memoryless non-linearity like peak clipping, time-varying gain from AGC and additive internal noise. PMID- 7997832 TI - Speech recognition in noise before and after a work-day's noise exposure. AB - A common complaint after a work-shift in high noise levels is fatigue, in the sense that listening to other people's spoken messages requires more effort than when well rested. The purpose of this study was to examine if this could be verified as reduced speech recognition in noise due to auditory fatigue. Speech recognition in noise, using low-redundancy sentence material, as well as pure tone hearing thresholds were tested on 13 subjects at the beginning and end of a 7-8 hours work-shift with equivalent noise levels in the range 78-90 dBA as measured by personal noise dose meters. Seven of the test subjects wore hearing protectors during work while six did not. No significant shift in mean values from the beginning of the work-shift to its end could be found, neither in speech recognition in noise nor in hearing thresholds for pure tones and neither for those wearing hearing protectors nor for those without. PMID- 7997833 TI - Extended high-frequency audiometry. Air- and bone-conduction thresholds, age and gender variations. AB - Air-conduction and bone-conduction thresholds have both been determined in the conventional audiometric frequency ranges and in the extended high frequencies through respectively 18 and 16 kHz for otologically healthy subjects in different age groups covering the age span 8-14 years through the eighth decade. Subjects younger than 30 years had conventional frequency air-conduction thresholds < or = 10 dB HL, whereas the corresponding thresholds of older subjects were within 0.1 and 0.9 percentiles of ISO 7029 (1984). Age- and gender-specific thresholds, medians and ranges, are presented for bone conduction in the extended high frequencies. Thresholds increase with both age and frequency in the range 8-16 kHz, and there is a largely non-significant tendency for thresholds to be higher in males. Threshold deterioration at the highest frequencies is already present at age 18-24 years compared with the youngest (8-14 year) age group. PMID- 7997834 TI - Interrelations between psychoacoustical tuning curves and spontaneous and evoked otoacoustic emissions. AB - With the hypothesis that cochlear active mechanisms are the origin of otoacoustic emissions (OAEs) and of the high frequency selectivity exhibited by the ear, psychoacoustical tuning curves (PTCs), transiently evoked otoacoustic emissions (TEOAEs), and spontaneous otoacoustic emissions (SOAEs) have been examined in 50 normal hearing subjects. Using a clinical simplified method, PTCs were successively assessed at three frequencies--1, 2 and 4 kHz--in each subject. The results showed the existence of significant differences in the quality of tuning (Q10dB) of the PTCs between, first, subjects having SOAEs and subjects having no SOAEs (Student's t-test; p < 0.05; df = 35) and, second, subjects having large TEOAEs and subjects having small TEOAEs (Student's t-test; p < 0.05; df = 14). Nevertheless, these significant differences did not appear for all the frequencies studied: the frequency selective relationship between PTCs and OAEs mainly involved the 2 kHz zone. Such results are discussed according to the specificities of the clinical method used for PTC measurement as well as to the spectral characteristics of OAEs. PMID- 7997835 TI - Internal speech functioning and speechreading in deafened and normal hearing adults. AB - The present study compared internal speech functioning in two groups of subjects: deafened and normal hearing adults. Internal speech functioning was assessed by means of either direct testing (i.e. rhyme-judgement tasks) or indirect testing (lexical access tests). No differences between the groups across tasks was obtained for speed. Neither was there any difference in accuracy level assessed by indirect tests. For direct testing the deafened group performed at a significantly lower level of accuracy. Accuracy was also correlated with the number of years that they had been deaf. It was concluded that one of the primary consequences of an acquired deafness is that the representational aspects of internal speech deteriorate over time, whereas the mechanical aspects remain relatively intact. Intercorrelations between accuracy level in direct testing and speechreading performance also suggest that speechreading ability declines. Clinical implications of the results are discussed. PMID- 7997836 TI - Screening for hearing loss in an at-risk neonatal population using evoked otoacoustic emissions. AB - The present study examines the performance of a transient evoked otoacoustic emissions hearing screening programme for neonates with risk factors for hearing loss. The programme has run for 5 years, and 772 babies with various risk factors have been screened using the Programmable Otoacoustic Emissions Measurement System (POEMS) designed by the Medical Research Council Institute of Hearing Research. Fourteen cases of significant hearing loss have been detected, with no false negative results. However, a very high false positive rate is reported, especially in babies with a birthweight of less than 1500 g. PMID- 7997837 TI - Otoacoustic emissions in the first year of life. AB - Transient evoked otoacoustic emissions (TEOAEs) were successfully recorded in 192 ears of 100 consecutive full-term neonates tested on the third or fourth postnatal day. A follow-up study was performed in 35 of these infants at the ages of 3, 6 and 12 months. The number of infants presenting decreased linearly with postnatal age. TEOAE amplitudes were largest in the youngest age group. Both the time required for testing each infant and the number of ears in which TEOAEs could not be identified increased with age. Otomicroscopical changes indicating secretory otitis media were found in all the latter ears. Recording of TEOAEs is a suitable method for screening peripheral auditory function in infants, and can be most successfully performed at the age of 3 or 4 days. PMID- 7997838 TI - Influence of the thickness of the skin and subcutaneous tissue covering the mastoid on bone-conduction thresholds obtained transcutaneously versus percutaneously. AB - Percutaneous and transcutaneous bone-conduction thresholds were obtained at 0.25, 0.5, 1, 2, and 4 kHz in 57 patients who were fitted with the Bone Anchored Hearing Aid (BAHA). Additionally, the thickness of the skin and subcutaneous tissue covering the mastoid was determined. No relation was found between the thickness of the skin and subcutaneous tissue, and the improvement in bone conduction thresholds at any of the frequencies, i.e. thresholds obtained percutaneously minus transcutaneously. The improvement (or deterioration) in speech recognition with the BAHA in a subgroup of patients who had previously used a (conventional) transcutaneous bone-conduction hearing aid was not related to the thickness of the skin and subcutaneous tissue layers. Therefore, the thickness of the skin and subcutaneous tissue layers measured pre-operatively cannot be used as a predictor of successful fitting with a BAHA. PMID- 7997839 TI - Myringoplasty. A conventional and extended high-frequency, air- and bone conduction audiometric study. AB - Comparison of the pre- and postoperative air- and bone-conduction thresholds in 22 subjects in whom successful myringoplasty was performed has been made in the conventional and extended high-frequency ranges. Air-conduction thresholds improved through 4 kHz, but were elevated postoperatively for the frequencies 6 through 18 kHz. Postoperative bone-conduction thresholds were elevated at 0.25 and 0.5 kHz, were lower by 2-8 dB for 1 through 3 kHz and not significantly altered in the extended high-frequency range of 8 through 16 kHz. The extended high-frequency air-conduction threshold loss following myringoplasty in this study is, therefore, due to changes in middle ear transmission and is not indicative of iatrogenic cochlear damage. PMID- 7997840 TI - Enhancement of fibrinolytic activity of human plasma in the presence of acetone. AB - The fibrinolytic system was studied in normal human plasma containing increasing concentrations of acetone up to 23.4 mmol l-1. Fibrinolytic activity measured as euglobulin clot lysis time [ECLT] and amidase activities toward chromogenic peptide substrates H-D-Valyl-L-Leucyl-L-Lysine-p-nitroanilide 2 HCl [S-2251], designed for plasmin determination, H-D-Valyl-L-Phenylalanyl-L-Lysine-p nitroanilide 2 HCl [S-2390], designed for the determination of t-PA in plasma via plasminogen activation and H-D-Prolyl-L-Phenyl-Alanyl-L-Arginine-p-nitro-anilide 2 HCl [S-2302], designed for the determination of kallikrein and activated Hageman factor, increased when 15.7 mmol l-1 concentration of acetone was reached. A parallel increase of esterolytic [substrate: naphthol-AS-acetate] activity was observed in euglobulin fractions. Crossed immunoelectrophoresis [CIE] revealed changes in fibrinogen profiles of plasma enriched with acetone as compared to native plasma. These findings suggest that acetone present in plasma in concentrations comparable to those found in some pathological states might activate fibrinolytic system. PMID- 7997841 TI - Lipoprotein(a) in smoking and non-smoking pregnant women. AB - Lipoprotein(a) (Lp(a)) levels were studied in 68 non-smoking and 118 smoking pregnant women and compared with a control group of 29 subjectively healthy, age matched non-smoking females. The median Lp(a) concentration of the total group of non-smoking pregnant women (123 mg l-1) surpassed significantly that of the pregnant smokers of comparable gestational age (64 mg l-1). The last group was not significantly different to the control group (67 mg l-1). Comparison of the smoking and non-smoking pregnant women showed significantly higher Lp(a) values during the last trimester of gestation (> or = 28 weeks) in non-smokers. The higher Lp(a) concentration in the plasma of non-smoking women during a normal pregnancy might be a physiological necessity. In that case lower levels of Lp(a), as seen in the last trimester of the smoking pregnant group, might be unfavourable for the normal development of the rapidly growing fetus in the last stage of the gestation. PMID- 7997842 TI - Purification and characterization of a human neutrophil lipocalin (HNL) from the secondary granules of human neutrophils. AB - A 45 kDa-protein was purified from the granules of human neutrophils. The protein consists of two apparently identical subunits. The isoelectric point was pH 8.40, and the molecular weight 45 kDa (unreduced) or 24 kDa (reduced). Treatment of the protein with Endoglucosidase F resulted in a reduction in the molecular weight to 20 kDa, indicating the presence of N-linked carbohydrate. The extinction coeffient was E1%,1cm = 13.76 at 280 nm. The 60 amino acid sequence revealed up to 65% sequence homology with rat alpha 2-microglobulin-related protein, which belongs to the lipocalin family. The protein co-sedimented with secondary (specific) granule marker proteins and correlated to the neutrophil content of Lactoferrin (r = 0.81, p < 0.001) and was estimated to be 0.59 microgram 10(-6) cells. Release studies showed that the neutrophils released 51.4 +/- 9.0% of the total cellular content of the protein when they were exposed to serum-opsonized particles, which was much higher than the release of Myeloperoxidase (12.7 +/- 3.5%) and Lactoferrin (22.9 +/- 4.7%). The N-terminal and four tryptic fragment amino acid sequence of the protein was identical with an N-formyl peptide binding 24 kDa protein and gelatinase associated protein of human neutrophils. In conclusion, we have purified and characterized a protein, human neutrophil lipocalin (HNL), from the secondary granules of human neutrophils and shown that it is readily mobilized from the neutrophils upon stimulation. PMID- 7997843 TI - A rapid method for determination of hepatic amino nitrogen to urea nitrogen conversion ('the Functional Hepatic Nitrogen Clearance'). AB - The Functional Hepatic Nitrogen Clearance (FHNC) is a measure of the functional liver mass as to conversion of amino-N to urea-N. FHNC is the slope of the linear regression of multiple samples (10-20) of urea-N synthesis rates (UNSR) on blood alpha-amino-N concentrations (alpha-AN) during infusion of amino acids. UNSR is measured as urinary urea-N excretion rate corrected for accumulation in total body water (TBW) and loss in gut. A simplified method which estimates FHNC from only two samples of UNSR and alpha-AN was developed. Urine was collected in two hourly intervals: before infusion of alanine, and from 2 to 3 h after start of alanine infusion. Blood-urea-N and alpha-amino-N was measured at the beginning and at the end of each urine sampling interval. TBW was estimated from a nomogram, and gut loss of urea was assigned a fixed value (14%). The two-sample FHNC was calculated as delta UNSR (mmol h-1)/delta mean alpha-AN (mmol l-1). Linear regression analysis of the two-sample estimates of FHNC on the 'true' multiple-sample values of FHNC in an independent population of control and cirrhotic subjects showed the two-sample estimates to be closely related with values of the multiple-sample method, the regression equation being: two-sample FHNC = -0.24 + 0.99 x multiple-sample FHNC, r2 = 0.98. A close relationship was also obtained when cirrhotic patients were considered alone: two-sample FHNC = 0.01 + 0.94 x multiple-sample FHNC, r2 = 0.98.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7997845 TI - Salt restriction in hypertension--the effect of dietary advice and self monitoring of chloride concentration in urine. AB - The aims of this present study were firstly to examine whether diet compliance and blood pressure effect could be enhanced by self monitoring with a titrator strip (Quantab 1176) measuring the urine chloride concentration. This was achieved by an open, randomized parallel group design. The study also sought to evaluate the blood pressure effect of a moderately salt restricted diet by using a pre-test-post-test design with a run-in period and controlling for relevant confounding factors (weight, training and alcohol consumption). Furthermore, the study aims were to validate the measurement of chloride concentration in the morning urine by the Quantab titrator strip. We compared Quantab 1176 measurement of chloride concentration in the morning urine with 24 h sodium excretion, determined by the clinical chemical laboratory, was performed. Twenty men and 14 women (mean age 53 years) with essential hypertension (mean: 165/96 mmHg) were observed during a run-in period of 4 weeks before randomization to either dietary advice combined with self monitoring of morning urine chloride concentration for 12 weeks, or dietary advice alone. The reduction in diastolic blood pressure of 6 mmHg was not different in the two groups (between groups p = 0.44). Within group changes of systolic blood pressure were 10 mmHg and 6 mmHg (p = 0.006 and p = 0.04) in the diet plus Quantab group, and the diet only group respectively (between groups p = 0.30). No significant difference in 24 h sodium excretion could be detected between the groups. The morning urine chloride concentration correlated moderately to the 24 h urine sodium excretion (r = 0.66, p < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7997844 TI - Generation of reactive oxygen intermediates in relation to short course chemotherapy in children suffering from pulmonary tuberculosis. AB - Functional status of phagocytes in relation to 6 months' short course chemotherapy of tuberculosis was studied with special reference to antigen-5 (Ag 5) of Mycobacterium tuberculosis. Phagocytic capacity and overall generation of reactive oxygen intermediates (ROI) measured as chemiluminescence (CL) response was studied in peripheral blood monocytes obtained from 20 children with pulmonary tuberculosis (PTb) and was compared with 20, age and sex matched, controls. In untreated children the CL response (mean +/- SD) with latex (0.90 +/ 0.08) and Ag-5 (0.99 +/- 0.11) was found to be severely depressed compared with controls (Latex, 19.2 +/- 5.10; Ag-5, 48.12 +/- 7.10). A significant improvement was seen in response to both the stimulants (Latex, 15.20 +/- 1.50; Ag-5, 28.15 +/- 7.32) after 3 months of therapy and became equal to, or slightly higher than, the values obtained with controls by the end of therapy. This study suggests that newly diagnosed untreated PTb is associated with an in vitro antigen specific compromise of phagocytic capacity and oxidative metabolic burst activity that is gradually and progressively corrected during the course of effective short course chemotherapy. In addition, Ag-5 is a potent stimulator of monocytes/macrophages; its potency being far greater than latex. PMID- 7997846 TI - Salt restriction and increased insulin production in hypertensive patients. AB - The present study was performed to evaluate glucose metabolism, serum lipids and sympathetic activity during 12 weeks of a moderate salt restricted diet in hypertensive patients. The study was designed as a pre-test-post-test study. All patients from a controlled trial evaluating self-monitoring of urine chloride concentration as a remedy for enhancing diet compliance and blood pressure effect were included. Twenty male patients and 14 female patients with essential hypertension (mean age 53 years) were randomized to a self monitoring diet group and a diet only group. They were exposed to a moderately salt restricted diet during 12 weeks. Fasting serum insulin C-peptide, glucose, HbA1c, total cholesterol, LDL-cholesterol, HDL-cholesterol and triglycerides were measured along with 24 h urine excretion of adrenaline, noradrenaline and vanillylmandelic acid (VMA). As a result, insulin C-peptide increased by 40% (p = 0.0001) whereas glucose rose by 6% (p = 0.02). Total cholesterol, LDL-cholesterol and HDL cholesterol concentration were reduced by 6% (p = 0.001), 12% (p = 0.008) and 11% (p = 0.004) respectively. HbA1c, serum triglycerides, total/HDL-cholesterol ratio, urine catecholamines and VMA were unchanged during the trial. It is concluded that salt restriction may increase insulin resistance in hypertensive patients. PMID- 7997847 TI - Twenty-five years of germinal centre physiology: implications for tolerance in the secondary B cell repertoire. AB - Twenty-five years ago, when I delivered the inaugural lecture of the Scandinavian Society for Immunology, my mind was filled with germinal centres because of the extraordinary antigen-capturing mechanism there, which depended on follicular dendritic cells trapping the antigen and holding it in an extracellular location for long periods of time, following which the germinal centre reaction developed around the antigen depot. It was apparent that germinal centres had much to do with immunological memory, but few functional details of their role were known. In the intervening period, a great deal of knowledge has accumulated about germinal centres, which have become known as the sites of extensive B cell proliferation, immunoglobulin variable region gene hypermutation, and selection of better antigen-binding variants leading to affinity maturation in the antibody response. Our laboratory's interest was reawakened when we came to examine the hypothesis that B lymphocytes destined to develop into memory B cells might pass through a 'second window' of tolerance susceptibility if they encountered antigen in the absence of T-cell help. We have constructed a model of tolerance dependent on the injection of soluble deaggregated antigen before or even up to 6 days after T cell-dependent challenge immunization. The model was intended to mimic what might happen if a B cell, developing correctly in a germinal centre, fortuitously mutates to acquire cross-reactivity to a soluble self antigen. We have shown that the surrogate self-antigen can profoundly impair the germinal centre process and virtually stop the emergence of high affinity memory B cells. PMID- 7997848 TI - The integrative activity of the immune system. PMID- 7997849 TI - Immunological abnormalities in patients with chronic fatigue syndrome. AB - Between January 1991 and January 1993, 265 patients who fulfilled the CDC criteria of the working case definition of Chronic Fatigue Syndrome (CFS) have been observed at our Institution and submitted for clinical and laboratory evaluation. One hundred and sixty-three patients were females and 102 males, the median age was 35 years (range 4-55 years); all patients reported profound and prolonged fatigue, lasting for a median of 3 years (range 6 months-10 years), preceded or accompanied at appearance by fever in 185 cases, and neuropsychologic problems including inability to concentrate, difficulty in thinking, confusion, irritability, forgetfulness, and depression. The fatigue was so severe that it required 102 patients to stop their working activities for a period of time ranging from 3 months to 2 years (range 7 months). In 40 consecutive patients a comprehensive immunologic testing by single and two-colour flow cytometry was performed and results compared with a group of 35 healthy, age- and sex-matched controls. Whilst no significant differences were found in the absolute numbers of circulating total T cells (CD3+) and of total helper/inducer (CD4+) or suppressor/cytotoxic (CD8+) T cells, an evident reduction in CD3-/CD16+ and CD57+/CD56+ NK lymphocytes along with an expansion of the CD8+/CD56+ and CD16 /CD56+ NK subsets, were found in the CFS group. In addition, CD56+ NK cells from CFS subjects were found to express an increased amount of cell adhesion molecules (CD11b, CD11c, CD54) and activation antigens (CD38). Both the percentage and absolute numbers of CD4+ T cells bearing the CD45RA antigen appeared significantly reduced in CFS patients, and CD4+ T lymphocytes from CFS subjects displayed an increased expression of the intercellular adhesion molecule-1 (ICAM 1/CD54). Finally, the total numbers of circulating (CD19+) B lymphocytes, were significantly higher in CFS cases than in controls, and in 11 out of 30 CFS patients the increase in circulating B cells was sustained by the expansion of the CD5+/CD19+ subset of B lymphocytes. We conclude that CFS is a syndrome not previously described in Italy, with already known clinical characteristics and appears to be associated with several immunologic abnormalities, including those reported previously in cohort of patients from different countries. We also show for the first time that CD56- NK cell subsets from CFS patients display an abnormally increased expression of cell adhesion molecules and activation markers. PMID- 7997850 TI - IgG subclass-associated differences in anti-schistosomal antibody specificity. AB - Consecutive sera from before and after treatment were collected from 23 patients with a Schistosoma mansoni infection, seven of whom had an early infection. All sera were analysed for IgG1, IgG3 and IgG4 antibody activity against three peptides from the protein Sm 28 GST (24-43, 115-131 and 140-153 aa). In addition, sera from 14 patients, four with an early infection and 10 patients with a chronic infection, were analysed for IgG and IgA antibody activity using seven peptides derived from the protein Sm 28 GST. This molecule has previously demonstrated protective activity against infection in various experimental models. The results are indicative of a subclass-related epitope specificity of the antibodies. Moreover, reactivity to one of the peptides (158-175 aa) was significantly associated with a chronic infectious status. PMID- 7997851 TI - T cells from children with IDDM are sensitized to bovine serum albumin. AB - Epidemiological and experimental evidence suggested that denial of dietary cow milk protein early in life protects genetically susceptible children and animals from insulin-dependent diabetes (IDDM). Bovine serum albumin (BSA) was proposed as a candidate milk-borne mimicry antigen responsible for the diabetogenic cow milk effect. Elevated anti-BSA antibodies have been observed in patients and diabetic rodents, and these antibodies precipitate p69 from islet cell lysates. IDDM is a T cell mediated disorder but efforts to detect BSA-specific T cells in diabetic children have so far failed. We describe here a culture system which allowed the detection of BSA-specific T cells and we mapped this response to the ABBOS peptide (pre-BSA position 152-169) previously identified as a possible mimicry epitope. ABBOS-sensitized T cells were found in 28/31 children with recent onset IDDM but not in non-diabetic controls nor in children with SLE or JRA. T cell proliferative responses declined within the first few years of diabetes diagnosis. Although no effector cell role for BSA/ABBOS specific T lymphocytes has been demonstrated, the presence of BSA peptide-specific T cells strengthens the postulated link between a cow milk protein and IDDM. PMID- 7997852 TI - Th1-like human T-cell clones recognizing Leishmania gp63 inhibit Leishmania major in human macrophages. AB - The major surface protease of Leishmania major, gp63, has been suggested as a vaccine candidate for cutaneous leishmaniasis. In this study gp63 was purified from L. major promastigotes. A panel of human T-cell clones recognizing this protein were generated from individuals who had previously had self-healing cutaneous leishmaniasis. The T-cell clones expressed CD4, and the alpha chain of the T-cell antigen receptor. GP63 reactive T-cell clones activated by antigen or by immobilized anti-CD3 antibody released relative large amounts of interferon gamma and no or little interleukin-4, thereby resembling Th1 cells. Autologous mononuclear cells and Epstein-Barr virus-transformed B cell lines were equally efficient in presenting the antigen to the T cells. The gp63 reactive T cells induced resistance to infection in cultured human macrophages by L. major. The data confirm that human CD4+ T cells recognizing gp63 can take part in the host defence against L. major infections. PMID- 7997853 TI - The expression of carbohydrate antigens in activated T cells and in autoimmune diseases. AB - Cell surface carbohydrate antigens have been implicated in cell differentiation and maturation and may play a role in immunoregulation. The expression of carbohydrates in peripheral blood lymphocytes (PBL) was studied by double immunofluorescence flow cytometry, using MoAbs CT1 and CT2 but only a small proportion of cells bound these MoAbs. MoAbs CT1, CT2 and the lectin vicia villosa (VV) which share specificity for Gal NAc were then used to examine lymphocytes from patients with systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), Behcet's disease (BD) and IgA nephropathy. A significant increase in MoAbs CT1 CT2 and VV binding CD4 or CD8 cells was found only with lymphocytes from patients with SLE. However, MoAbs CT or VV binding lymphocytes from healthy subjects were significantly up-regulated by activation with a mitogen (PHA), cross-linked anti-CD3 MoAb or a common antigen (65kDa heat shock protein), suggesting that an increased proportion of T cells expressing these carbohydrates results from any of the three types of lymphocyte activating agents. Inhibition studies were then carried out to determine the relationship between the MoAbs CT1 and CT2, VV and GalNAc. Indeed, VV binding to T cells was significantly inhibited by either MoAbs CT1 or CT2, or GalNAc but not GlucNAc, suggesting that VV shares a common binding site with MoAb CT and that GalNAc may constitute one of the sugar receptors. Investigations of lymphocytes from adult peripheral blood in health and disease suggest that carbohydrate antigens may play a role in activation and immunoregulation. PMID- 7997854 TI - IgG humoral response against the antigen 85 complex homologues in leprosy. AB - Antigen 85 complex is the major protein component present in M. bovis BCG culture filtrate (CF). It consists of a family of three proteins: 85A, 85B and 85C. Combining isoelectric focusing and Western blot analysis, we have previously identified different antigenically related proteins present in the CF of other mycobacteria (M. tuberculosis, M. kansasii, M. avium, M. gordonae, M. fortuitum and M. phlei) using monoclonal antibodies (MoAbs) directed against the antigen 85 complex of M. bovis BCG. Humoral immune response directed against these cross reactive homologues was analysed in sera from 20 patients with multibacillary leprosy (BL/LL), from 20 patients with paucibacillary leprosy (BT/TT) and from 15 healthy leprosy contacts. All the antigen 85 homologues identified in the seven CFs by MoAbs were also recognized by IgG present in sera from multibacillary leprosy patients, but not or very faintly in sera from paucibacillary leprosy patients or from healthy subjects. These results suggest that some of the M. leprae epitopes inducing a significant humoral response in multibacillary leprosy are common to the various 85 antigenically related proteins present in all mycobacterial species. PMID- 7997855 TI - Role of the bowel flora for development of immunity to hsp 65 and arthritis in three experimental models. AB - An infectious aetiology in rheumatoid arthritis (RA) has for long been suggested, although no conclusive evidence for this is at present available. Lately a large interest has been devoted to the involvement of heat shock proteins (hsps) in autoimmune disorders due to their conserved structure and immunogenic properties. Immunity to hsps has been observed both in human autoimmune conditions and in experimental models of autoimmune disease. We have studied the role of the bacterial flora and hsp immunity in the arthritic response in three experimental models of arthritis; type II collagen arthritis (CIA), adjuvant arthritis (AA) and oil induced arthritis (OIA); by using germ free and conventional DA rats. A high incidence of severe arthritis developed in all the models evaluated irrespectively of whether the animals were in the conventional or germ free state. This confirms earlier results which show a minor effect of the bacterial flora in CIA and AA in high responder strains. These results also show that a severe OIA can develop in germ free animals. Despite the severe arthritic response induced, no serum antibody levels to hsp 65 could be detected in the germ free animals, which was in contrast to the conventional animals where a positive anti-hsp 65 serum response was seen in 35-80% of the animals with CIA, AA or OIA. These results show that development of a humoral response to hsp 65 in these models of arthritis is dependent on the presence of a bacterial flora. Further, the lack of humoral immunity in germ free animals despite a severe arthritic response indicates that humoral immunity to hsp 65 is not involved in development of disease in these three models of experimental arthritis. PMID- 7997856 TI - Non-diabetogenic insulitis in NOD<-->B10.GD allophenic mice in spite of permissive class I MHC antigens. AB - Allophenic mice (embryo aggregation mouse chimeras) enable us to dissect the process of spontaneous autoimmunity under physiological conditions. Our previous experiments showed that the autoimmune process in allophenic mice of the NOD<- >C57B1/6 strain combination does not progress from insulitis to diabetes. One possible explanation for this protection is that H-2 Kd-restricted CD8+ T cells kill only NOD beta cells (Kd,Db) in the chimeric islets, while the B6 beta cells (Kb,Db) are spared from destruction. To test this hypothesis we analysed 22 NOD<- >B10.GD chimeras in which the class I MHC are shared by both parental strains. Therefore all the beta cells in these chimeras express H-2 Kd molecules. Ten allophenic mice were killed at 7 weeks and studied for early pathology. No evidence for intra-islet infiltration was obtained at this age, suggesting that the autoimmune process in NOD<-->B10.GD chimeras is slower than in NOD mice. Twelve chimeras were followed up for 1 year for disease development and all failed to progress to full-blown diabetes, despite the occurrence of intra insulitis in six out of 12 mice. The lack of disease in NOD<-->B10.GD chimeras demonstrates that class I MHC chimerism does not account for diabetes resistance in NOD-allophenic mice. PMID- 7997857 TI - Characterization of a functional null cell line derived from NZB x NZW)F1 mice. AB - We attempted to establish a null cell line from NZB x NZW(B/W)F1 mice in order to investigate a regulatory role of null cells during polyclonal B cell activation in autoimmune diseases. NB2.2, a representative subclone of resulting null cell lines, was maintained in long-term tissue culture with 10% mouse ConA supernatant (MCAS). Interestingly, the cell free supernatant of the NB2.2 cells (NB-CFS) showed marked synergistic effects on IgM secretion by B cells induced by IL-5. In addition, NB-CFS had the ability to augment the production of autoantibodies against bromelain-treated mouse red blood cells (BrMRBC) and single-stranded DNA (ssDNA) by B cells induced by IL-5. To determine whether NB2.2 cells induce polyclonal B cell activation and autoantibody generation in vivo, BALB/c mice were injected with NB2.2 cells. The results showed that the level of anti-ssDNA antibodies in sera of BALB/c mice injected with NB2.2 cells was significantly higher than that of control BALB/c mice injected with FDC-P2 cells. In addition, splenic B cells from mice injected with NB2.2 cells significantly proliferated in vitro in response to IL-4 and IL-5, and produced anti-ssDNA antibodies in the presence of IL-5. These results suggest that NB2.2, a null cell line established from B/WF1 mice, produces mediators capable of promoting polyclonal B cell activation and inducing autoantibody secretion, and that this kind of null cell may play an important role in the pathogenesis of autoimmune diseases. PMID- 7997858 TI - Effects of human calprotectin (L1) on in vitro immunoglobulin synthesis. AB - Calprotectin (L1) is a major cytoplasmic protein of neutrophilic granulocytes and monocytes/macrophages which is released from leucocytes during activation or cell death. Apart from in vitro antimicrobial and antiproliferative activity little is known about the biological function of the protein. Since previous investigations have shown that calprotectin plasma levels are elevated in various inflammatory rheumatic diseases, we wanted to investigate if calprotectin has an effect on immune cell functions. Peripheral blood mononuclear cells, either unstimulated or polyclonally stimulated with mitogen, were incubated with calprotectin and effects were assessed by enumeration of immunoglobulin secreting cells (ELISPOT). The results indicate that incubation with high concentrations of calprotectin (> 64 micrograms/ml) inhibit the production of the three classes of immunoglobulins investigated (IgG, IgM and IgA), both for mitogen stimulated and unstimulated lymphocytes. Except for the highest concentration of calprotectin (500 micrograms/ml), it seems plausible that the observed inhibitory effect of calprotectin on Ig production is not a result of a direct toxic effect of calprotection on B lymphocytes. Altogether, these effects of high calprotectin levels might be of importance in the immunoregulation of inflammatory conditions. PMID- 7997859 TI - [Acute pulmonary and cardiovascular effects of continuous axial rotation (kinetic therapy) in respiratory failure]. AB - AIM: Continuous lateral rotational therapy (kinetic therapy) is advocated to improve pulmonary gas exchange in patients with severe respiratory failure, by promoting mobilization of secretions and reducing mismatch of ventilation and perfusion. We analyzed the acute pulmonary and hemodynamic changes before and after beginning kinetic therapy in critically ill patients with inotropic support. PATIENTS AND METHODS: Due to severe respiratory failure, 18 patients with "systemic inflammatory response syndrome" had been placed in a kinetic bed (Rotorest, KCI Mediscus). Retrospective analysis included several indices of arterial oxygenation, intrapulmonary "shunt fraction", cardiac index, arterial and pulmonary arterial pressure, systemic vascular resistance and systemic oxygen consumption. RESULTS: After the start of kinetic therapy, we found a statistically significant improvement of pulmonary gas exchange and a reduction of shunt fraction 12 hours later. Cardiac index and arterial and pulmonary arterial pressure remained unchanged. Systemic oxygen consumption was increased. CONCLUSION: The continuous axial rotation of patients with severe respiratory failure results in a prompt improvement of arterial oxygenation. Even in hemodynamically unstable patients we did not observe harmful effects. PMID- 7997860 TI - [Endocarditis due to Corynebacterium diphtheriae cause by contact with intravenous drugs: report of 5 cases]. AB - The clinical features of 5 patients with invasive disease due to nontoxigenic Corynebacterium diphtheriae are presented. 4 patients had proven left sided endocarditis, and one had probable endocarditis of the mitral valve. 4 patients were intravenous drug abusers, and one had a girl friend who was also an iv-drug abuser. Only one patient had antibodies against human immunodeficiency virus. 2 patients with endocarditis of the mitral or the aortic valve, and one patient with endocarditis of a prosthetic aortic valve, died of septic complications. All patients or their partners frequented the same community of drug abusers. Since the blood culture isolates shared common features for biotyping, resistance patterns and also for ribotyping in three tested patients, we assume that all patients were infected by the same clone of C. diphtheriae. Drug abusers may become a new reservoir for C. diphtheriae infection. Along with our patients, we present an overview of the 49 published cases of C. diphtheriae endocarditis. PMID- 7997861 TI - [Small area variations: surgery for hip fractures in the canton of Vaud]. AB - OBJECTIVES: Studies of small area variations of health care utilization are more and more frequent. Such variations are often considered to be an indication of variations in the quality of medical care. The variations in the rate of operations for hip fractures are among the lowest studied to date, due to the fact that a consensus exists concerning this surgery. Our objective is to examine these variations within the context of relatively small and heterogeneous districts. METHOD: Based on anonymous computerized data on public hospital stays, this study describes the variations in population rates (crude and standardized) of operations for hip fracture among the health districts of the Canton of Vaud for the period from 1986 to 1991. District populations vary from 22,000 to 164,000. Using the extremal quotient (EQ), the importance of these variations was determined. RESULTS: The study population consists of 2363 cases, of which 78% are women. Mean age is 80.4 for women and 70.6 for men. Standardized rates of operation for hip fracture per 100,000 in the Canton Vaud for the years 1986 to 1991 are, respectively: 56; 67; 86; 91; 89 and 94. The EQ for the years 1986 to 1991 are respectively: 8.2; 4.0; 3.5; 2.7; 1.9 and 1.9. The high EQ, especially for the earlier years, are contrary to the initial premise of absence of variation. The progressive implementation in the Canton Vaud of VESKA medical statistics could play a role, as could the small size of many of the districts, with resultant instability of rates. CONCLUSIONS: Considering the wide variations shown here for an operation hardly regarded as subject to variations, it is important to exercise caution in interpreting published data of small area variations. PMID- 7997863 TI - [Which analgesic dosage of paracetamol?]. AB - The purpose of this study was to evaluate the dose-response of paracetamol and to assess its plasma concentration-effect relationship. According to a randomized, double-blind, and placebo controlled design healthy volunteers (n = 11) received 0.5, 1 and 2 g paracetamol (as propacetamol) intravenously (15 min). The extent of analgesic effect was measured over 8 hours by objective pain threshold (R-III) monitoring after selective transcutaneous electrical stimulation of the ipsilateral sural nerve. Maximal R-III threshold increase is at 2 hours after 0.5 g and 2.5 hours after 1 g and 2 g. The delayed peak effects, when compared to peak plasma concentrations, draw counter clockwise hysteresis. Duration of paracetamol antinociceptive effect increased concomitantly to dosage increment. Intravenous paracetamol exerts a dose-dependent central analgesia. PMID- 7997862 TI - [Addison crisis due to bilateral adrenal gland histoplasmosis]. AB - A 44-year-old man was admitted with symptoms compatible with Addison crisis. Abdominal computer tomography revealed extensive bilateral adrenal abscesses. Histoplasma capsulatum was cultured from a needle aspirate. The patient was HIV seronegative and had no underlying malignancy. He may have acquired the infection during several stays in endemic areas in the United States, South America and Asia. The case was also remarkable for moderate brain atrophy, thrombosis of the portal and splenic veins and liver cirrhosis caused by alpha-1-antitrypsin deficiency (phenotype MZ). The patient recovered fully under substitution of adrenal hormones and antifungal treatment. He received intravenous amphotericin B (75 mg q24h) for 10 days, followed subsequently by oral treatment with itraconazole (400 mg q24h) over several months. Radiologic follow-up 9 and 18 months later showed a pronounced decrease of the inflammatory adrenal lesions. PMID- 7997864 TI - Brain storm. Controlling chaos could help treat epilepsy. PMID- 7997865 TI - Cerebrospinal meningitis epidemics. PMID- 7997866 TI - Why children talk to themselves. PMID- 7997867 TI - Trends in biological research. Big-time biology. PMID- 7997869 TI - EMBL and European cooperation in the life sciences. PMID- 7997868 TI - Funding of newly submitted NIH grant applications. PMID- 7997870 TI - Expressed sequence tags. PMID- 7997871 TI - Italy keeps EMBL anxiously waiting. PMID- 7997872 TI - Piot named head of new UN unit. PMID- 7997873 TI - The company that genome researchers love to hate. PMID- 7997874 TI - Is a new virus the cause of KS? PMID- 7997875 TI - A need to reinvent biotechnology regulation at the EPA. PMID- 7997876 TI - Upsetting the balance of forces in DNA. PMID- 7997877 TI - Cell cycle control and cancer. AB - Multiple genetic changes occur during the evolution of normal cells into cancer cells. This evolution is facilitated in cancer cells by loss of fidelity in the processes that replicate, repair, and segregate the genome. Recent advances in our understanding of the cell cycle reveal how fidelity is normally achieved by the coordinated activity of cyclin-dependent kinases, checkpoint controls, and repair pathways and how this fidelity can be abrogated by specific genetic changes. These insights suggest molecular mechanisms for cellular transformation and may help to identify potential targets for improved cancer therapies. PMID- 7997878 TI - DNA bending by asymmetric phosphate neutralization. AB - DNA is often bent when complexed with proteins. Understanding the forces responsible for DNA bending would be of fundamental value in exploring the interplay of these macromolecules. A series of experiments was devised to test the hypothesis that proteins with cationic surfaces can induce substantial DNA bending by neutralizing phosphates on one DNA face. Repulsions between phosphates in the remaining anionic helix are predicted to result in an unbalanced compression force acting to deform the DNA toward the protein. This hypothesis is supported by the results of electrophoretic experiments in which DNA spontaneously bends when one helical face is partially modified by incorporation of neutral phosphate analogs. Phasing with respect to a site of intrinsic DNA curvature (hexadeoxyadenylate tract) permits estimation of the electrostatic bend angle, and demonstrates that such modified DNAs are deformed toward the neutralized surface, as predicted. Similar model systems may be useful in exploring the extent to which phosphate neutralization can account for DNA bending by particular proteins. PMID- 7997879 TI - Identification of herpesvirus-like DNA sequences in AIDS-associated Kaposi's sarcoma. AB - Representational difference analysis was used to isolate unique sequences present in more than 90 percent of Kaposi's sarcoma (KS) tissues obtained from patients with acquired immunodeficiency syndrome (AIDS). These sequences were not present in tissue DNA from non-AIDS patients, but were present in 15 percent of non-KS tissue DNA samples from AIDS patients. The sequences are homologous to, but distinct from, capsid and tegument protein genes of the Gammaherpesvirinae, herpesvirus saimiri and Epstein-Barr virus. These KS-associated herpesvirus-like (KSHV) sequences appear to define a new human herpesvirus. PMID- 7997880 TI - Toxic shock syndrome toxin-1 complexed with a class II major histocompatibility molecule HLA-DR1. AB - The three-dimensional structure of a Staphylococcus aureus superantigen, toxic shock syndrome toxin-1 (TSST-1), complexed with a human class II major histocompatibility molecule (DR1), was determined by x-ray crystallography. The TSST-1 binding site on DR1 overlaps that of the superantigen S. aureus enterotoxin B (SEB), but the two binding modes differ. Whereas SEB binds primarily off one edge of the peptide binding site of DR1, TSST-1 extends over almost one-half of the binding site and contacts both the flanking alpha helices of the histocompatibility antigen and the bound peptide. This difference suggests that the T cell receptor (TCR) would bind to TSST-1:DR1 very differently than to DR1:peptide or SEB:DR1. It also suggests that TSST-1 binding may be dependent on the peptide, though less so than TCR binding, providing a possible explanation for the inability of TSST-1 to competitively block SEB binding to all DR1 molecules on cells (even though the binding sites of TSST-1 and SEB on DR1 overlap almost completely) and suggesting the possibility that T cell activation by superantigen could be directed by peptide antigen. PMID- 7997881 TI - Subsets of HLA-DR1 molecules defined by SEB and TSST-1 binding. AB - Superantigens bind to major histocompatibility complex class II molecules on antigen-presenting cells and stimulate T cells. Staphylococcus aureus enterotoxin B (SEB) and toxic shock syndrome toxin-1 (TSST-1) bind to the same region of human lymphocyte antigen (HLA)-DR1 but do not compete with each other, which indicates that they bind to different subsets of DR1 molecules. Here, a mutation in the peptide-binding groove disrupted the SEB and TSST-1 binding sites, which suggests that peptides can influence the interaction with bacterial toxins. In support of this, the expression of the DR1 molecule in various cell types differentially affected the binding of these toxins. PMID- 7997882 TI - Specification of C/EBP function during Drosophila development by the bZIP basic region. AB - The biologically relevant interactions of a transcription factor are those that are important for function in the organism. Here, a transgenic rescue assay was used to determine which molecular functions of Drosophila CCAAT/enhancer binding protein (C/EBP), a basic region-leucine zipper transcription factor, are required for it to fulfill its essential role during development. Chimeric proteins that contain the Drosophila C/EBP (DmC/EBP) basic region, a heterologous zipper, and a heterologous activation domain could functionally substitute for DmC/EBP. Mammalian C/EBPs were also functional in Drosophila. In contrast, 9 of 25 single amino acid substitutions in the basic region disrupted biological function. Thus, the conserved basic region specifies DmC/EBP activity in the organism. PMID- 7997883 TI - Potentiated transmission and prevention of further LTP by increased CaMKII activity in postsynaptic hippocampal slice neurons. AB - Calcium-calmodulin-dependent protein kinase II (CaMKII) is a necessary component of the cellular machinery underlying learning and memory. Here, a constitutively active form of this enzyme, CaMKII(1-290), was introduced into neurons of hippocampal slices with a recombinant vaccinia virus to test the hypothesis that increased postsynaptic activity of this enzyme is sufficient to produce long-term synaptic potentiation (LTP), a prominent cellular model of learning and memory. Postsynaptic expression of CaMKII(1-290) increased CaMKII activity, enhanced synaptic transmission, and prevented more potentiation by an LTP-inducing protocol. These results, together with previous studies, suggest that postsynaptic CaMKII activity is necessary and sufficient to generate LTP. PMID- 7997884 TI - High-performance size exclusion chromatography and polyacrylamide gel electrophoresis for characterization of unfractionated and low molecular mass glycosaminoglycans. AB - The microheterogeneity of glycosaminoglycans was analyzed using HPSEC and PAGE. GAG preparations were analyzed five times to determine the standard deviation of the average molecular mass and the polydispersity P of each GAG with HPSEC. In addition, the Kav coefficient, the area under the absorbance time curve, and the peak purity were determined as mean and standard deviation. PAGE was performed five times using the same preparations and the average molecular mass and polydispersity were calculated. The results of PAGE and HPSEC were compared and the molecular mass distribution of the two methods was shown. The advantage of PAGE is the higher sensitivity and the resolution of oligosaccharides. The advantage of HPSEC is the better standardization, higher reproducibility, and speed. PMID- 7997885 TI - Nuclear magnetic resonance analysis of human urine: influence of intravenous and oral administration of glycosaminoglycans. PMID- 7997887 TI - Modulation by transforming growth factor-beta 1 and interleukin-1 beta of proteoglycan release and chondrodisaccharide composition in porcine articular cartilage. AB - The effects of IL-1 beta and TGF-beta 1 on proteoglycan release and modifications in porcine articular cartilage explants are described. Proteoglycan release in culture medium was markedly increased when cartilage was treated with IL-1 beta (5 to 100 ng/mL). Addition of IL-1 beta alone or in combination with TGF-beta 1 to cartilage culture stimulated the production and release of PGE2. Indomethacin (10(-6) M) did not modify the IL-1 beta effect on proteoglycan release. Both the spontaneous and IL-1 beta-induced proteoglycan release were downregulated by TGF beta 1 (50 ng/mL). Basal and stimulated loss of proteoglycans was reduced by the addition of cycloheximide (10(-6) M) and by metalloprotease inhibitors. GAGs of conditioned medium and extracellular matrix proteoglycans were digested to about 90% by chondroitin ABC lyase, suggesting that CS is the major GAG present. Structural analysis of disaccharides, by CZE, revealed a different pattern of oxysulfation when cartilage explants were treated either with IL-1 beta or TGF beta 1. Indeed, analysis of GAGs, released into the medium from TGF-beta 1 treated cartilage, showed a reduction in the level of 4-S-disaccharide (delta Di4S and an increase in desulfated disaccharides delta Di0S). In the extracellular matrix, IL-1 beta and TGF-beta 1 induced a more complex rearrangement of the GAGs, in that the levels of delta Di0S and delta Di4S were increased whereas those of delta Di6S were decreased. Altogether, these results suggest that TGF-beta 1 does not only counteract the effect of IL-1 beta on proteoglycan release, but modifies the structure of GAGs, probably by interfering with the activity or the synthesis of sulfotranspherases involved in GAG biosynthesis. PMID- 7997886 TI - Gas-liquid chromatography-mass spectrometry analysis of anticoagulant active curdlan sulfates. AB - 1. To evaluate the sulfation pattern of anticoagulant active curdlan sulfates, a methylation method, based on the synthesis of alkylated alditol acetates, followed by GLC-MS examination, was developed. 2. By the specific cleavage of the sulfate esters, using solvolysis and the substitution of these liberated OH groups with ethyl iodide, a third kind of substitution was introduced in the alkylated alditol acetates, specifically replacing the former sulfate esters. 3. The primary OH group in position 6 had more than the 10-fold accessibility to sulfation, in comparison to the secondary OH groups in positions 2 and 4. 4. Products with a low DS were fairly homogenously substituted, having unsubstituted or selectively C6-sulfated glucose units. Increasing DS was associated with a loss of homogeneity as well as selectivity of the C6 sulfation. 5. Sulfation of C6-protected curdlan resulted in products with a higher content of sulfate groups in positions 2 and 4, and consequently a uniform charge distribution around the glucose monomer. 6. Besides the dependence on the DS and the MW, also the sulfation pattern influenced the anticoagulant activity. The higher the portion of the secondary linked sulfate esters, the higher the anticoagulant activity. The C6-protected curdlan sulfates had activities normally corresponding to higher DS and MW. PMID- 7997888 TI - Preparation and characterization of deuterium-labeled glycosaminoglycans. AB - Heparin, NAcHep, DS, and CS were labeled with deuterium by N-reacetylating, with the deuterated acetic anhydride (CD3CO)2O, GAGs previously N-deacetylated (by hydrazinolysis) to the desired extent. Degrees of deuteration of the present preparations, as determined by 2H- and 1H-NMR were 15%, 51%, 49%, and 79% for heparin, NAcHep, DS, and CS, respectively. The NMR analysis (including the 13C spectra) of the labeled products indicated that deuterium labeling did not involve any substantial modification of the GAG structures. Also NMR signals associated with specific sequences of heparin for antithrombin and of DS for heparin cofactor II were essentially the same in the unlabeled and in the deuterated GAGs. The substantial retention of the original structure was confirmed by data on the degree of sulfation (by conductimetry) and on the electrophoretic mobility in acid buffer. On the other hand, HPLC/SEC data indicated some depolymerization of heparin and DS in the N-deacetylation step of the labeling reactions. HPLC/MS spectrometry permitted a clear identification of disaccharide and tetrasaccharide fragments obtained from deuterated GAGs by enzymic (heparinase, chondroitinase ABC) or chemical depolymerization (deaminative cleavage, Smith degradation), opening new prospects for studies of human pharmacokinetics, with differentiation of exogenous from endogenous GAGs. PMID- 7997889 TI - Derivatives of bis-aldonic acid amides and their anticoagulant and antithrombotic properties. AB - Aprosulate sodium was the first representative of a new class of synthetic polyanions showing antithrombotic efficacy in different animal models. In several clinical trails (Phase I) in human volunteers aprosulate demonstrated anticoagulant properties, too. Searching for other active substances of similar structure, a series of bis-aldonic acid amides were synthesized. These compounds exhibited interesting antithrombotic and anticoagulant activities. The pharmacodynamic activities of the compounds LW 10121, LW 10125, LW 10114, 10244, and LW 10168 are summarized in this article. These substances prolonged the APTT to 150% of the blank values at concentrations of 1.5 to 13.5 micrograms/mL. The thrombin time and anti-Xa test were only slightly influenced by concentrations up to 100 micrograms/mL. All compounds were investigated in a jugular vein hemostasis model in rats to examine their antithrombotic potential. They all had an antithrombotic activity lower than aprosulate, except compound LW 10121, which seemed to be a little more active. The subcutaneous injection of 10 mg/kg LW 10121 resulted in a longer duration of action than aprosulate and heparin. On the basis of the chemical structure and the profile of action, it is assumed that the new compounds may possess the same mode of action as aprosulate, but the mechanism of action may be different from heparin and low molecular weight heparins. PMID- 7997890 TI - Semisynthesis and analysis of lipophilically modified unfractionated and low molecular mass heparins. AB - Unfractionated heparin and LMMH were substituted with different lipophilic organic compounds. Specifically endpoint attached (LMMH-tyramine and LMMH tyramine-FITC) and nonspecifically substituted heparins (acylated heparins, and LMMH-biotin and LMMH-cholesterol hemisuccinate) were obtained. The lipophilically substituted heparins were analysed by HPSEC and showed different retention times, high peak purity, different UV/VIS absorbances, and areas under the absorbance time curve. The determination of the average molecular mass Mn, Mm, and Mz and the polydispersity P was performed by PAGE. The substituted heparins showed an increase in their molecular mass Mm, ranging from 2.9 to 129.7% unfractionated heparin and 3.9 to 224.0% (LMMH) compared with the parent compounds (unfractionated heparin and LMMH). The anticoagulant activity was measured by anti-Factor Xa. Lipophilically modified heparin had an aXa activity ranging from 52 to 168 U/mg (unfractionated) and 60 to 108 U/mg (LMMH) and antithrombin activity ranging from 31 to 270 U/mg (unfractionated) and 5 to 15 U/mg (LMMH). The thrombin generation inhibition assay demonstrated an effective anticoagulant potency of the modified compounds. They were neutralized by different amounts (1.1 to 4.1, w/w) of protamin. 1H NMR spectroscopy revealed the specific endpoint attachment of tyramine to LMMH and FITC to LMMH-tyramine. The lipophilically modified heparins showed intact anticoagulant properties and are now used for pharmacokinetic investigations. PMID- 7997891 TI - Comparison of three heparin bovine serum albumin binding methods for production of antiheparin antibodies. AB - IgG antiheparin antibody secreting hybrid cells have not been successfully raised so far. Therefore, we compared three different conjugating procedures for preparation of LMMH-protein conjugates. Albumin was chosen as carrier protein. Only the conjugate prepared by reductive amination induced antiheparin antibody production in mice. Conjugates prepared by the carbodiimide method and Mannich reaction did not induce heparin immunogenicity and did not induce antibody production in mice. Antiheparin antibody production in mice and by hybrid cells was detected by assaying serum and culture supernatant. LMMH-tyramine, labeled with 125I, was bound by the antibodies and immunoprecipitated by goat anti-mouse IgG antibodies. The tracer was competitively inhibited by nonlabeled heparin for binding to the heparin antibodies. Hybridoma cells producing the specific antiheparin antibody were cloned and subcloned up to monoclonality. Six hybrids were selected and designated H1.18, H1.21, H3.1, H3.17, H3.18, H4.24. In conclusion, six monoclonal antiheparin antibodies were raised using a LMMH albumin conjugate prepared by reductive amination. PMID- 7997893 TI - Inhaled beta 2-adrenergic agonists in asthma: the evolving dilemma. AB - Inhaled beta 2-adrenergic agonists have been used in the treatment of asthma since the 1970's. They are extremely effective bronchodilators in all situations of bronchoconstriction, and are generally well tolerated by patients. The recent advent of long-acting beta 2-adrenergic agonists will extend the clinical applications of this group of drugs. On the other hand, doubts have recently emerged on the safety of inhaled beta 2-adrenergic agonists. Recent well controlled studies also examined the manners whereby inhaled beta 2-adrenergic agonists are used in asthmatics, and the long term effects on lung functions. Although at least two decades have passed since the introduction of inhaled beta 2-adrenergic agonists, strategies on their optimum use have only emerged from these recent findings. This review briefly discusses as the most important developments leading to the rationalisation of the way inhaled beta 2-adrenergic agonists should be used in clinical asthma. PMID- 7997892 TI - Extraction methods of glycosaminoglycans from biologic fluids. PMID- 7997894 TI - Benign epilepsy of childhood with centrotemporal spikes. PMID- 7997895 TI - Smoking restriction in workplaces. PMID- 7997896 TI - Malaysian children with: "benign epilepsy of childhood with centrotemporal spikes". AB - Benign epilepsy of childhood with centrotemporal spikes (BECT) was studied in Malaysian children, and was observed in Chinese, Malay and Indian children in the ratio 10:6:5. There were 12 boys and 9 girls. Fit frequency varied from almost daily to a single fit. The age of onset ranged from 2-13 years and BECT was not noted in any child over 13 years old. There was a strong circadian rhythm and fits occurred mainly in sleep. Generalised seizures were more common than partial seizures. During the 3-year study from April 1989 to April 1992, 21 children with BECT were identified from the EEG records done at the University Hospital and it was found that this genetic epilepsy which is autosomal dominant with age dependent penetrance occurs in approximately 4.8% of our epileptic children. In addition there were 3 children in whom petit mal co-existed with a BECT EEG trait. PMID- 7997897 TI - Smoking restrictions in private workplaces in Singapore. AB - This survey aims to determine the number and profile of private workplaces in Singapore which have a smoking restriction policy. The response rate was 43%. Of the companies which responded, 59% had some form of smoking restriction. Private companies are more likely to have a smoking restriction policy: (a) where smoking poses inherent fire risks, such as those dealing with inflammable chemicals or gases; (b) where smoking poses inherent detrimental effects to the quality of the products, such as those dealing with precision electronic microcomponents, where a smoke-free and dust-free environment is essential; (c) are larger companies; and (d) have strong management support in initiating and enforcing smoking restriction. Future programmes should give more emphasis to the service industries such as construction, insurance, banking and finance, and smaller companies (with fewer than 100 employees). They should involve the management who play an important role in implementing smoking restriction at their workplace. PMID- 7997898 TI - Current logistics of acute burn care in Singapore. AB - OBJECTIVE: To study logistic requirements in acute burn care in Singapore and to correlate statistics on fire, unnatural deaths and burns. DESIGN: Fire data (from Singapore Fire Safety Bureau), mortality data (from Institute of Science & Forensic Medicine) and burn data (from Burns Centre, Singapore General Hospital) were studied. SETTING: Severe burn victims often require prolonged treatment. Useful data was obtained in a 1,500-bed restructured government hospital. PARTICIPANTS: All reported and investigated fire incidents, coroner enquiries of unnatural deaths and admitted burn patients. INTERVENTION: General burn data obtained retrospectively from 398 burn admissions in 1988 and logistic burn data from 41 patients requiring fluid replacement regime. RESULTS: Fire data showed one burn admission in every 12 fires (398/4718), one burn death in every 314 fires (15/4174) or 55 unnatural deaths (15/828). Mortality data showed 15 burn deaths, two prior to admission, 7/13 admitted died of suicidal injuries and mortality rate was 3.3% (national annual average is 1.9%). General burn data showed adults 76% and children 24%, 3:1 male predominance; scalds (46%), fire (32%), explosions (11%) and others (11%). Seventy-eight patients (adults 58, children 20) required fluid resuscitation. Logistic burn data (average burn 35%, 28 partial thickness and 13 full thickness burns) were: ALOS 19.5 days, 2.4 major operations per patient (range 2-7), 56 minor procedures and 2.9 L blood transfusion per patient (those who were operated required 3.8 L and those not operated, 1 L per patient). Blood investigations increased with severity and pattern of injury, Acinetobacter species was commonest microorganisms, antibiotics were used in 66% of patients and commonest burn dressings were tullegra (T/G), followed by T/G with silverzine. CONCLUSION: Data presented useful for correlation of fire, mortality and burn statistics, resource allocation and new burn facility establishment. PMID- 7997899 TI - An unusual course and relations of the human axillary artery. AB - The axillary artery was studied by dissection of 50 human cadavers over a two year period. Except in one instance, the course and relations of the axillary artery of all the other cadavers conformed to the normal description found in standard textbooks of Anatomy. In the exceptional cadaver, the axillary artery of the right side showed two unique features: (1) it pursued a tortuous course and made two sharp bends, and (2) it was situated superficial, rather than deep to, the pectoralis minor muscle. Its branches and relationship to the brachial plexus were also altered. On the left side, the artery was not tortuous but was also situated in front of the pectoralis minor. The present observation has several implications: (1) such a configuration of the artery would render it more prone to kinking and hence compression; (2) surgically, it might make axillary block of the brachial plexus and block dissection of the axillary lymph nodes during radical mastectomy more difficult; (3) it is at risk during infraclavicular percutaneous cannulation of the subclavian vein for a central line insertion or for insertion of a subclavian cannula for haemodialysis. PMID- 7997901 TI - Abdominal trauma--a review. AB - Trauma is a leading cause of death in the 1-44 age group. In our study, the most common cause is road traffic accidents followed by stab wounds and falls from height. Blunt abdominal trauma accounted for 79% of the cases. The spleen and liver were the most common organs involved in blunt abdominal trauma. Clinical assessment of blunt abdominal trauma is unreliable. The diagnostic peritoneal lavage is a useful triage tool in the initial assessment. PMID- 7997900 TI - The medical, social, and functional profile of Parkinson's disease patients. AB - The study looked at the medical, social, and functional aspects of 34 patients with idiopathic Parkinson's Disease (PD). Eighty-five percent were above 55 years and 35% were over 70 years. Twenty-four (71%) were males. Most patients had Stage II disease. Overall functional state of the patient correlated closely with the stage of Parkinson's disease. Patients were likely to be dependent if their disease severity was stage III or more. Eighteen (53%) patients would require a carer to be present at least part of the day and 3 (9%) patients would require a carer most of the time. Domestic chores such as meal preparation, housework, and shopping were also affected in most of those who were previously active in these tasks. Ten patients had given up work due to their Parkinson's disease. The lack of knowledge of the disease was shown both in the carers and the patients. Twenty nine of the patients had no knowledge of the disease, and only one carer had superficial knowledge of the disease. The major social problems associated with the disease were loss of social contact, behavioural problems, family members under strain and communication problems within the family. Since Parkinson's Disease is a chronic illness, with associated disabilities, it is important that the physician should aim for a multidisciplinary approach. Patient and carer education should be given emphasis, and the many everyday functional problems addressed. Advice on life-style management and aids to overcome disabilities may help improve quality of life of the patient and reduce carer's stress. PMID- 7997902 TI - Evaluation of two antiemetic agents during outpatient gynaecological surgery. AB - Thirty-two adult female ASA I patients (American Society of Anesthesiologists' grading) undergoing voluntary termination of pregnancy (VTP) under general anaesthesia were randomly divided into three groups. Patients received 0.6 mg/kg pentazocine intravenously five minutes prior to induction of anaesthesia along with either isotonic saline, or promethazine 0.5 mg/kg or metoclopramide 0.2 mg/kg. Anaesthesia was induced with intravenous thiopentone and maintained with nitrous oxide in oxygen and boluses of thiopentone. Vomiting and sedation were scored at the end of anaesthesia, one hour later and at the time of discharge. The mean vomiting score was comparable in the three groups. Though the mean dose of thiopentone used was significantly less in the promethazine group, the sedation scores and the duration of stay in the clinic were comparable in all the groups. It is concluded that promethazine and metoclopramide in the doses used are ineffective as antiemetic agents in outpatient gynaecological patients. PMID- 7997903 TI - An investigation into complaints of wrist pain and swelling among workers at a factory manufacturing motors for refrigerators. AB - In 1987, a group of workers complained through their union that some of them developed wrist pain and swelling from the manual handling of heavy stators. The complaints were from the morning shift of a particular assembly line in a factory making motors for refrigerators. The precipitating factor appeared to be the change in the weight of the model assembled. The new stator weighing 5.8 kg was about twice as heavy as the previous model. Each worker on the line handled 300 to 1,000 stators per shift. The work involved including lifting the stators onto and off the conveyor belts and pushing and pulling them along horizontal planes. To evaluate the problem, workers from both shifts of the affected assembly line were interviewed and examined. A total of 79 workers (all females) was involved. The presence and severity of work-related aches, pains, numbness, swelling, etc over the last 4 weeks were enquired. The nature of the work done in the line was observed. Sixty-three out of 79 workers had some symptoms giving an overall prevalence rate of 79.8%. The two most common complains were pain (90.5%) and numbness (28.6%). The most commonly affected sites were the hands and wrist followed by the neck and shoulder. There was no significant difference in the prevalence of symptoms among workers in the 2 shifts. The symptoms were subjective and associated with job dissatisfaction and there was no difference in the average number of stators handled between those with symptoms and those without.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7997904 TI - An outbreak of methicillin-resistant Staphylococcus aureus in a neonatal intensive care unit in Singapore: a 20-month study of clinical characteristics and control. AB - Methicillin resistant Staphylococcus aureus (MRSA) is a major infection control problem in many countries. There have been many reports of outbreaks in neonatal nurseries including, in our part of the world, Australia, Hong Kong and Malaysia. A recent outbreak of MRSA in the neonatal intensive care unit in the Kandang Kerbau Hospital, Singapore, presented us with the opportunity to study the clinical characteristics of the outbreak and the effects of infection control measures. Neonates admitted to the neonatal intensive care unit were studied over a 20-month period. They were all screened for nasal colonisation on admission and weekly thereafter. Infections were documented. Over this period there were altogether 2,576 admissions of which 85 infants had nasal colonisation with MRSA (3.3%) and 28 developed infections (1%). Although the majority of infants colonised by MRSA suffered no ill effects, 3 had septicaemia and 2 had septicaemia with osteomyelitis. There were no deaths. Standard infection control measures with barrier nursing and the use of mupirocin nasal ointment were ineffective, and control was achieved only after strict cohorting together with the use of mupirocin was instituted. This was done without additional costs to the department and without additional nurses or doctors. PMID- 7997905 TI - Bacteroides fragilis meningitis. AB - Bacteroides fragilis is an obligate anaerobic bacillus residing in the normal intestinal flora of the colon. Anaerobic bacterial meningitis due to this pathogen is rarely diagnosed and if present, a predisposing source of infection should be actively sought for. Anaerobic cultures of cerebrospinal fluids should be done for patients with meningitis, especially those with concomitant pathologies that predispose to anaerobic infections. Two cases of anaerobic meningitis due to Bacteroides fragilis, one associated with cholesteotoma and the other with nasopharyngeal carcinoma, are reported. Both were successfully treated with metronidazole. PMID- 7997906 TI - Deep vein thrombosis: a study in clinical diagnosis. AB - Recently, three patients presented with deep vein thrombosis-like symptoms and signs but were negative on venogram. Three questions arose: Was the clinical diagnosis accurate? What is the accuracy of the diagnostic test used? What is the time taken for the clot to lyse? To answer the first question, a retrospective clinical study was done. For the other two I did a literature search. For the clinical study, I analysed thirty patients with venogram proven deep vein thrombosis (DVT) and five patients with DVT-like clinical findings but four were venogram negative and one was ultrasound negative. The results showed that symptoms and almost all the clinical signs were useless in differentiating these two sets of patients. Swelling was very sensitive but not specific and the Homan's sign was very specific for DVT but not very sensitive and would be of use only in a case by case basis. Other significant findings were that DVT was more common in the Chinese than the other races and more common in females. The incidence of DVT is also particularly marked in the 30-39 and 70-79 age groups. It was also found that venograms were very accurate in diagnosing DVT but need to be read by two experienced radiologist. Also it was found that clot lysis can take place as early as 35 hours after starting heparin but vessel changes remain for at least 11 weeks.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7997907 TI - The family doctor's role in the care of the elderly. AB - With the anticipated increase in the number of aged persons in our local population, there will be an increased workload for the family doctor caring for the elderly in the community. Diseases thought to be attributed to ageing may be non-degenerative and hence treatable. This paper highlights the role of the family physician in the care of the elderly as the doctor's recognition of these diseases and consequent early intervention may result in an improved outcome for the patient. Optimal care can be achieved with the family doctor's systematic planning of the individual's care, networking with hospitals and other health professionals and providing support for carers. PMID- 7997909 TI - Current therapy of HIV associated infections and malignancies. AB - Drug therapy in AIDS is used to prolong life as there are many infections and malignancies which appear as a consequence of the immunosuppression and these can be fatal. Current anti-virals which specifically inhibit HIV replication are being used earlier to extend quality of life, maintain immune status and reduce the prevalence of opportunisitic infections and malignancies. Some infections cannot yet be treated and new therapies are awaited. It is too early in the epidemic for significant drug resistance to emerge. However, this is to be expected in the future. The prevalence of adverse drug reactions is significantly increased and therefore newer alternatives are keenly awaited. Drug treatment of HIV infected individuals is a formidable task requiring skilled multidisciplinary approach. This review summarises the most current treatment modalities for HIV associated infections and malignancies. PMID- 7997908 TI - Warning symptoms of sinister headache. AB - Headache is a common complaint. In most patients, it is usually a problem of migrainous or tension-type headache. It is crucial that a physician is able to differentiate sinister causes of headache from the more benign ones. Six cases are presented to illustrate the fact that there are clues in the history to suggest a sinister cause of headache even though there are minimal or no neurological deficits on physical examination. At some point of time, these cases were examined by a senior physician but they were diagnosed as migrainous or tension-type headaches. The first case is a 41-year-old labourer with cryptococcal meningitis. He presented with severe headaches at a relatively late age. A 20-year-old female complained of the worst headache she ever had and this was due to a subarachnoid haemorrhage. The third case was a young woman with a large parietal meningioma. Her headaches had recently assumed a different character. The fourth case involved an investment manager who developed headaches with transient diplopia and projectile vomiting and investigations revealed an ependymoma. A shipyard worker complained of a constant headache which disturbed his sleep. Two weeks after medical consultation, the character of his headache changed and he developed diplopia in all directions of gaze. He succumbed to pituitary apoplexy. The final case is a 28-year-old woman who had a complicated migraine. CT scan of the brain showed a large arterio-venous malformation. PMID- 7997910 TI - Renal tubular acidosis in Kelantan, Malaysia--a case review. AB - Renal tubular acidosis (RTA) is a defect in urinary acidification in the absence of renal failure. All records of patients admitted to adult medical wards at the University Hospital USM (HUSM), Kelantan between 1986 to 1990 with the diagnosis of renal tubular acidosis were reviewed. Sixteen (16) patients were identified and fulfilled the diagnostic criteria. Their mean age at presentation was 28.9 +/ 0.74 years. The triad of muscle weakness, hypokalaemia and systemic metabolic acidosis were the characteristic features at presentation. Normal serum alkaline phosphatase and skeletal X-rays were noted. Their prognosis were generally good. Their mean serum bicarbonate and potassium on follow up were 17.84 +/- 0.35 and 3.82 +/- 0.05 mmol/L respectively. The importance of regular follow-up and long term management is emphasised. PMID- 7997911 TI - The Beri-Beri Hospital, Singapore (1907-1925). AB - The high incidence of Beri-beri in the 1890s and 1900s coupled with the ignorance of its causation led to many forms of treatment, culminating in the establishment of a "specialised hospital" in Singapore. However, the "anti-beri-beri" factor in unpolished rice soon made this hospital redundant. PMID- 7997912 TI - A man with dilated cardiomyopathy and a slow heart rate. PMID- 7997913 TI - Singapore infectious diseases comes of age. PMID- 7997914 TI - Update of the rapid diagnosis of infectious diseases. I: Bacteria, fungi and parasites. AB - The application of monoclonal antibodies and DNA probes in the clinical microbiology laboratory has resulted in an array of rapid diagnostic tests. The immunofluorescent assay or enzyme-linked immunoassay is widely used in the rapid diagnosis of bacteria eg Group A streptococcus, Legionella pneumophila, Mycoplasma pneumoniae, Bordetella pertussis; parasites eg Chlamydia tachomatis, Cryptosporidium species; and fungi eg Pneumocystis carinii. The BACTEC system was first introduced to detect bacteraemia pathogens. It has been further developed to detect Mycobacterium species in clinical specimens and this has greatly reduced turn-around time in the laboratory diagnosis of Mycobacterium species. The discovery of the polymerase chain reaction has led to hopes of using it as a potential diagnostic tool in the microbiology laboratory. PMID- 7997915 TI - Massive haematoma from digital massage in an anticoagulated patient: a case report. PMID- 7997916 TI - Caecal mass on barium enema study--a case for routine colonoscopy. AB - Prolapse of the ileal mucosa through the ileo-caecal valve or minor ileo-caecal intussuception is not uncommon and may occasionally be mistaken radiologically for a caecal neoplasm, especially if intestinal obstruction, abdominal pain or rectal bleeding is present. Colonoscopic visualisation and biopsy is important before surgery is advised. We describe a case of ileal mucosa prolapse masquerading as a caecal neoplasm on barium enema study. Colonoscopy showed prolapse of the ileal mucosa which was easily reduced by air insufflation and therefore unnecessary surgery was avoided. PMID- 7997917 TI - Polymyositis associated with symptomless nasopharyngeal carcinoma. AB - We describe a 42-year-old Chinese patient with polymyositis and nasopharyngeal carcinoma. The polymyositis was complicated by respiratory failure needing mechanical ventilation despite conventional therapy. Treatment of the carcinoma was associated with recovery of muscle strength. To our knowledge this is the first reported association of polymyositis with nasopharyngeal carcinoma. PMID- 7997918 TI - Radiological diagnosis of accidental oesophageal intubation. AB - Oesophageal intubation is rapidly fatal if not recognised. We report a patient who not only survived an oesophageal intubation but who had chest X-rays taken which showed an oesophageal intubation which was initially recognised by the attending physician. PMID- 7997920 TI - Developing a valid and reliable measure of health outcome for patients with low back pain. AB - OBJECTIVE: The authors developed and validated a measure of health outcome for patients with low back pain. RESULTS: A questionnaire was developed incorporating the type of questions asked when taking a clinical history. After testing on a sample of 568 patients, three questions were discarded from the questionnaire. The final questionnaire was found to be reliable and valid in the sense that patients' scores correlated highly with their scores on a general health profile and with GP perceptions of severity. Health status in patients with low back pain was significantly impaired when compared with the general population. CONCLUSION: A clinically based questionnaire, together with a general measure of health, can provide a valid and reliable package for the routine assessment of perceived health in patients with low back pain. PMID- 7997919 TI - Return to work/work retention outcomes of a functional restoration program. A multi-center, prospective study with a comparison group. AB - STUDY DESIGN: This was a study of a standardized functional restoration program that included 11 centers in seven states, involving 303 patients in the treatment group and 94 patients in the comparison group. OBJECTIVE: To illustrate the positive effect a functional restoration program has on return to work rates and work retention regardless of previous surgical intervention. SUMMARY OF BACKGROUND DATA: Data were obtained from the initial and discharge evaluations as well as at 6- and 12-month follow-up. METHODS: Patients received a standardized work capacity assessment upon entrance and were recommended to the program if they adhered to specific entrance criteria. Treatment patients received the same evaluation at discharge. RESULTS: Significant improvement in functional abilities, actual return to work, and work retention were noted in the treatment group regardless of treatment intervention. CONCLUSIONS: This study demonstrated improved return to work rates and work retention with surgical and nonsurgical patients after their participation in a functional restoration program. PMID- 7997922 TI - Foraminal lumbar disc herniation. Experience with 83 patients. AB - STUDY DESIGN: This study analyzed a series of 83 patients operated on for foraminal lumbar disc herniation. OBJECTIVES: This study sought to develop clinical and radiologic diagnoses, evaluate interlaminar and extra-articular exposures, and evaluate postoperative results. SUMMARY OF BACKGROUND DATA: Some authors have reported a specific clinical syndrome, but other reports have indicated the clinical picture is indistinguishable from usual posterolateral disc herniation. Surgical management often has been compared between the interlaminar and extra-articular approaches. METHODS: Clinical findings were reviewed. All patients were evaluated with computed tomography, but radiologic diagnosis required computed tomographic discography for 26 patients. Interlaminar exposure with partial medial facetectomy was performed in 73 patients and an extra-articular approach was necessary in 10 patients. Postoperative results were evaluated with a 2-year follow-up. RESULTS: Foraminal lumbar disc herniations have a specific clinical picture, particularly severe radicular signs. Precise preoperative radiologic evaluation is essential for successful operative procedure. Postoperative results were good in 76% of the patients. The other patients felt mild residual radicular pain, although no residual root compression was found on postoperative computed tomography. Only 21% of the patients that had a radicular deficit recovered totally. CONCLUSIONS: Foraminal lumbar disc herniation involves characteristic clinical features. Radiologic diagnosis requires high-resolution computed tomography, computed tomographic discography, or magnetic resonance imaging. Most foraminal lumbar disc herniations are reached through the interlaminar exposure extended to the upper lamina and medial facet without total facetectomy. An extra-articular approach should be reserved for extra-foraminal herniations. PMID- 7997921 TI - Outcome of lumbar fusion in Washington State workers' compensation. AB - STUDY DESIGN: This study covered a large, population-based cohort of workers in the Washington State workers' compensation system who received lumbar fusion between August 1, 1986 and July 31, 1987 to determine work disability status, reoperation rate, and patient satisfaction. OBJECTIVES: To use predictors of outcome of lumbar fusion to design clearer clinical guidelines for lumbar fusion in injured workers. METHODS: Logistic regression analysis was used to determine the predictors of work disability and risk of reoperation after fusion. RESULTS: The lumbar fusion incidence rate was 41.7/100,000 workers a year (n = 388 patients). Overall, 68% were work disabled and 23% required further lumbar spine surgery 2 years post-fusion. Five markers of severity predicted worse work disability outcome (older age at injury, longer time from injury to fusion, increased increased time on work disability before fusion, increased number of prior low back operations, and increased number of levels fused). Even after adjusting for these variables, receiving instrumentation with fusion doubled the risk of reoperation. Most patients reported that back pain (67.7%) was worse and overall quality of life (55.8%) was no better or worse than before surgery. CONCLUSIONS: Outcome of lumbar fusion performed on injured workers was worse than reported in published case series. Prospective studies should be conducted to determine the biologic indications that might lead to improved outcomes in this disabled population. PMID- 7997923 TI - A comparative analysis of spondylolysis repair. AB - STUDY DESIGN: This retrospective study compared patient outcome after two surgical techniques for pars interarticularis repair: 1) buck screw fixation and 2) the modified Morscher-designed spondylolysis distraction hook. OBJECTIVES: To determine whether one technique was associated with higher radiographic, clinical, or implant failure. SUMMARY OF BACKGROUND DATA: Both techniques have been reported as giving good clinical results. METHODS: Twenty patients were included in this study. All patients had Type IIA spondylolytic defects with either a Grade 0 or Grade I spondylolisthesis. Nine patients were treated with the Morscher hook implant, and 11 patients were treated with the Buck technique. RESULTS: Radiographic follow-up of the Morscher implants demonstrated loosening in three and breakage in one. Radiographic analysis of the Buck technique demonstrated implant failure in one. Failure of healing occurred in four instances with the Morscher implant compared with two instances with the Buck technique. Clinical outcome was assessed using the modified Prolo score. The mean outcomes were 6.33 in the Morscher group and 6.09 in the Buck group. CONCLUSIONS: In these patients, the Morscher implant had a high failure rate. Furthermore, the clinical outcome in this group of patients was poor using either technique. PMID- 7997924 TI - Treatment of L5-S1 spondyloptosis by staged L5 resection with reduction and fusion of L4 onto S1 (Gaines procedure). AB - STUDY DESIGN AND OBJECTIVES: A retrospective study was performed on the two-stage Gaines procedure for the treatment of spondyloptosis, evaluating indications, techniques, results, and patient satisfaction. SUMMARY OF BACKGROUND DATA: Sixteen consecutive patients from two institutions were included. Their average age was 24 years. Average follow-up was 3.9 years, with 11 patients included in follow-up 2 or more years. Ten patients (63%) had a preoperative neurologic deficit--three with cauda equina syndrome, one with foot drop. All patients had severe back or radicular symptoms and significant disability or severe deformity. METHODS: Patient examinations, interviews, chart review, and radiographic measurements all were performed independently. A subjective questionnaire was administered to each patient comparing preoperative with postoperative changes in pain, function, and appearance, as well as their overall outcome assessment. RESULTS: Postoperatively, 12 patients (75%) had early neurologic deficits, with seven of these having had a preoperative deficit. Four of these seven had a persistent deficit at follow-up, one with a permanent foot drop and three with documented weakness that was still improving at follow-up. The patient with preoperative foot drop remained unchanged, and the remaining seven patients with early deficit all recovered within 1 year. All three patients with preoperative cauda equina syndrome recovered postoperatively. The subjective questionnaire results revealed extremely high patient satisfaction. They reported significant improvement in pain, function, and appearance. CONCLUSIONS: Despite the relatively high complication rate, with appropriate patient selection, planning, and surgical technique, this procedure appears to be a sound method for treating severe cases of spondyloptosis, yielding very high patient satisfaction. PMID- 7997926 TI - Progressive congenital scoliosis treatment using a transpedicular anterior and posterior convex hemiepiphysiodesis and hemiarthrodesis. A preliminary report. AB - STUDY DESIGN: Patients treated with a transpedicular anterior and posterior convex hemiepiphysiodesis and hemiarthrodesis for progressive congenital scoliosis were followed to evaluate this treatment. OBJECTIVE: To evaluate an alternative to a separate anterior approach for performing an anterior hemiepiphysiodesis for progressive congenital scoliosis. SUMMARY OF BACKGROUND DATA: Previous investigators have reported a transpedicular anterior fusion combined with a bilateral posterior fusion. The authors are unaware of a previous report on a transpedicular anterior convex hemiepiphysiodesis and fusion combined with a unilateral convex posterior spinal fusion to treat progressive congenital scoliosis. METHODS: Nineteen curves were fused in 16 patients who had a variety of congenital anomalies. The average age at surgery was 4.8 years (range, 11 months to 13 years) The average follow-up period was 4.8 years (range, 2 to 9.6 years). RESULTS: The average preoperative and postoperative fused curves measured 36 degrees and 38 degrees, respectively. Of the 19 fused curves, seven curves (37%) improved, eight curves (42%) were unchanged or progressed less than 7 degrees, three curves (16%) progressed 10 degrees to 15 degrees, and one curve (5%) progressed more than 15 degrees. CONCLUSIONS: This procedure appears to be most effective in arresting growth in the young patient who has an isolated hemivertebrae and no excessive kyphosis. The epiphysiodesis effect is less predictable. PMID- 7997925 TI - Adult idiopathic lumbar scoliosis. A formula for prediction of progression and review of the literature. AB - STUDY DESIGN: A retrospective study was conducted of patients with untreated adult-type idiopathic lumbar scoliosis. OBJECTIVES: To construct a mathematical formula that provides accurate progression of an idiopathic adult lumbar scoliosis using initial roentgenographic parameters. SUMMARY OF BACKGROUND DATA: Osteoporosis, lateral spondylolisthesis of L2-L4, and degeneration of disc and joint may contribute to a poor prognosis for lumbar adult-type scoliosis. METHODS: Seven roentgenographic parameters taken from the standing roentgenograms of 91 patients with a scoliosis of more than 10 degrees Cobb angle and who were included in a follow-up for more than 2 years, were put into a multiple regression analysis to observe the relative weight of each in the progression of the scoliosis. RESULTS AND CONCLUSIONS: Only lateral spondylolisthesis of the apical vertebra, Harrington factor, and disc index were related to progression of the scoliosis. Using the mathematical formula, the real progression of lumbar scoliosis can be predicted within an average of 0.85 degrees +/- 3.76 degrees. PMID- 7997927 TI - Transpedicular fixation with Zielke instrumentation in the treatment of thoracolumbar and lumbar injuries. AB - STUDY DESIGN: Sixty-five patients who underwent transpedicular fixation for thoracolumbar and lumbar injuries were studied for type of injury, the severity of paralysis, the degree of postoperative correction, and instrumentation failures. OBJECTIVES: To evaluate the surgical approaches and the selection of instrumentation to determine indications for using the transpedicular fixation procedure. SUMMARY OF BACKGROUND DATA: Various transpedicular fixation devices have been used for different type of injuries, and satisfactory postoperative results were not obtained in some studies. METHODS: Forty patients had burst fractures, 19 had fracture dislocations, and six had chance-type fractures. An anterior decompression procedure was used for most cases of burst fracture and some cases of fracture dislocation where anterior compression factors were present. The Zielke or modified Zielke system was used as an internal fixator for posterior segmental fixation. RESULTS: No patient had neurologic deterioration after surgery. Twenty of 28 patients with incomplete lesions improved postoperatively according to Frankel grades. The instrumentation failed in only one patient, in whom a nonunion developed. CONCLUSION: With transpedicular fixation, it is possible to provide solid internal fixation that is circumscribed to the injured vertebral segments. The elasticity of the Zielke rod makes it an excellent transpedicular fixation device because it is easily attached and reduction is easily performed. Anterior decompression with fusion needs to be used with transpedicular fixation in the treatment of injuries (especially burst fractures). PMID- 7997928 TI - Paraspinal precontraction does not enhance isokinetic trunk extension performance. AB - STUDY DESIGN: This study investigated the influence of isometric contraction of the trunk extensor muscles, immediately preceding maximum effort isokinetic trunk extension (precontraction), on isokinetic performance variables and activation levels of the paraspinal muscles. OBJECTIVES: To determine whether agonist precontraction significantly improved the concentric and eccentric isokinetic trunk extension contraction. SUMMARY OF BACKGROUND DATA: Agonist precontraction has been reported to enhance agonist neural drive and force output of the knee and ankle joints. METHODS: Subjects performed concentric and eccentric isokinetic trunk extension at 60, 90, and 120 deg/sec, each of which were preceded by isometric trunk extension precontraction force equal to 0%, 25%, and 50% body weight. RESULTS: Concentric and eccentric contractions showed general, but no statistically significant performance enhancement with paraspinal precontraction. Eccentric contractions tended to improve to a greater extent than concentric contractions. CONCLUSIONS: It is possible that the addition of agonist precontraction increased the complexity of the trunk extension task, thus requiring a learning period, as is the case with most novel motor skills. There may be meaningful rehabilitation-related implications of the qualitative tendencies observed in the data that merit further consideration. PMID- 7997929 TI - The strength and stiffness of thoracic implant anchors in osteoporotic spines. AB - OBJECTIVE: To gain a better understanding of factors affecting dorsal implant pull-out strength and stiffness so thoracic spinal implant fixation can be improved. METHODS: Posterior pull-out testing of six thoracic implant anchor types was performed on 54 osteoporotic human vertebra, T2-10, with an average bone mineral density of 0.67 g/cm2. RESULTS: The mean loads at neural arch failure were similar (296 to 382 N). Pedicle strength was greatest at T2 and least at T3. Hook claws were stiffer than sublaminar wires (121 N/mm and 180 N/mm versus 42 N/mm and 52 N/mm, respectively). Facet hook and pedicle hook claws were comparable, as were subpars wires. Bone mineral density of the vertebral bodies correlated with the stiffness of the sublaminar wire anchors only. CONCLUSION: To optimize the strength and stiffness of implant constructs designed to resist forward flexion, this study supports using hook-claws rather than sublaminar wires and extension of fixation to T2 when clinically realistic. PMID- 7997930 TI - Isokinetic and non-dynamometric tests in low back pain patients related to pain and disability index. AB - STUDY DESIGN: This study compared isokinetic and non-dynamometric tests for their correlation with subjective low back pain symptoms. METHODS: A total of 185 patients with chronic low back pain were examined. RESULTS: The repetitive arch up and sit-up tests correlated significantly with pain and disability (Million index) both in men and women (r ranged from -0.39 to -0.46; P < 0.001). In women, the isokinetic trunk flexion and extension tests and the non-dynamometric tests correlated equally well with the Million index. In men, the isokinetic flexion and extension tests had weaker correlations. Overall, the isokinetic lifting tests showed lower correlations than did the isokinetic trunk extension tests. In the isokinetic flexion and extension tests, fast testing speeds (120 degrees/sec and 150 degrees/sec) correlated somewhat better with the subjective symptoms than did the lowest speed (30 degrees/sec). CONCLUSIONS: The non-dynamometric tests are still useful in clinical practice in spite of the development of more accurate muscle strength evaluation methods. PMID- 7997931 TI - Reported pain during lumbar discography as a function of anular ruptures and disc degeneration. A re-analysis of 833 discograms. AB - STUDY DESIGN: This re-analysis was based on 833 computed tomography/discograms collected from 306 candidates for back surgery. OBJECTIVES: The goal was to test the hypothesis that outer anular ruptures are the main determinant of the pain of discography. SUMMARY OF BACKGROUND DATA: Previous analyses indicated univariate associations of pain with disc degeneration and anular ruptures. METHODS: If present, pain was classified as "exact", "similar", or "dissimilar" reproduction of the previously experienced pain. For each disc, ruptures and degeneration were separately evaluated by a four-point scale. Multiple logistic regression with random effects was used in the analysis. RESULTS: Outer anular ruptures were the only predictor of the responses "similar" and "exact". General disc degeneration was the only predictor of the response "dissimilar". There was no effect modification due to gender, age, and spinal level. CONCLUSIONS: During discography, the outer anulus appears to be the origin of pain reproduction. PMID- 7997932 TI - Computed tomography after laminectomy for lumbar spinal stenosis. Patients' pain patterns, walking capacity, and subjective disability had no correlation with computed tomography findings. AB - OBJECTIVES: The purpose of this study was to evaluate the relationship between postoperative computed tomography findings and patients' pain patterns, walking capacity, and subjective disability after laminectomy for lumbar spinal stenosis. SUMMARY OF BACKGROUND DATA: Recent improvements in computed tomography have enabled this tool to reveal changes in a patient after an operation, but there is a paucity of comparative examinations regarding the lumbar spinal canal of asymptomatic and symptomatic patients after laminectomy for lumbar spinal stenosis. METHODS: Ninety-two patients (42 women, and 50 men) with a mean age of 55 years were operated upon. Mean follow-up time was 3.5 years. Based on computed tomography findings of the operative area, three patient groups were formed: 1) no stenosis, 2) moderate stenosis, 3) and severe stenosis. During treadmill testing, each patient's pain was evaluated by visual analogue scale. The patients were divided into four pain pattern groups: 1) pain in the back and leg, 2) pain in the back only, 3) pain in the leg only, and 4) no pain in the back and leg. Subjective disability was measured by the Oswestry disability score. RESULTS: The structural changes revealed by computed tomography, and the patients' pain patterns, walking capacity, and subjective disability did not correlate significantly with each other. CONCLUSIONS: Postoperative computed tomography has only limited value because asymptomatic and symptomatic patients yield similar findings after surgery for lumbar spinal stenosis. PMID- 7997933 TI - Describing the size of lumbar disc herniations using computed tomography. A comparison of different size index calculations and their relation to sciatica. AB - STUDY DESIGN: The study compared different methods to measure the absolute and relative size of lumbar disc herniations on computed tomography scans and their relation to sciatica. METHODS: Computed tomography (CT) examinations were done before and at 3 and 24 months after nonoperative treatment in 30 patients with lumbar disc herniations. The size of the herniation was described by different indexes and related to the degree of sciatica. One index was formed by the area of the herniation in relation to the spinal canal (A-index), whereas two indexes were formed by linear measurements of the herniation in relation to the spinal canal in either two (ST-index) or one direction (S-index). RESULTS: Each index was correlated significantly to the degree of sciatica. The area of the herniations decreased markedly over time. CONCLUSIONS: Linear measurements of the herniation in two perpendicular directions provide a practical and accurate way of describing the size of lumbar disc herniations. PMID- 7997934 TI - Percutaneous transpedicular biopsy of the spine. AB - STUDY DESIGN: Despite increasing information regarding pedicular instrumentation, the transpedicular biopsy of the vertebral body has not been popularized. The precise technique for percutaneous transpedicular biopsy and the volume of the vertebral body accessible through the pedicle has not been reported. OBJECTIVE: To describe the percutaneous transpedicular biopsy, its diagnostic yield, to determine the amount of bone retrievable through the pedicle. SUMMARY OF BACKGROUND DATA: Experience gained from open biopsy facilitates the development of the percutaneous technique. There were no complications with the open or closed procedures. METHODS: Transpedicular biopsy was performed on 18 patients (nine open and nine percutaneous). Unilateral transpedicular curetments were performed on the cadaveric lumbar spines. The volume of the vertebral body accessible through the pedicle was determined using roentgenograms, computed tomography, and image analysis. RESULTS: Adequate specimens for a correct diagnosis were obtained in all biopsies. Laboratory volumetric analysis demonstrated that more than 50% of the volume of a lumbar vertebral body is accessible through a unilateral transpedicular approach, without compromising the anatomic structure of the pedicle. CONCLUSIONS: The vertebral pedicle provides a safe conduit for biopsy of most vertebral body lesions. Percutaneous transpedicular biopsy can be performed with minimal morbidity and high diagnostic yield. PMID- 7997935 TI - Fibrocartilaginous mesenchymoma of the fifth lumbar vertebra treated by vertebrectomy. AB - STUDY DESIGN: This is the first report of a fibrocartilaginous mesenchymoma in the spine. SUMMARY OF BACKGROUND DATA: This is a rare bone tumor composed of islands of hyaline cartilage in a collagen-producing spindle cell stroma. Seven cases of fibrocartilaginous mesenchymoma have been reported previously. Of these, four occurred in the long bones. METHODS: The tumor is hypercellular with mild nuclear hyperchromasia. Few mitotic figures are present. However, it is highly infiltrative, and in the present patient, it completely encircled the spinal cord. Vertebrectomy was required to ensure tumor eradication. RESULTS: Five years after tumor resection, femoral head allograft replacement of the vertebral body, and posterior spinal stabilization, there was no evidence of tumor recurrence. PMID- 7997937 TI - Jean-Andre Venel. PMID- 7997936 TI - Spine update. The use of animal models to study spinal fusion. AB - The outcome of a spinal fusion depends upon a multifactorial process. Therefore, it is difficult and impractical to study individual variables clinically. Animal models have been useful in studying the parameters that influence the spinal fusion process. Despite the knowledge gained from previous animal studies, there exists a large void in our basic understanding of this complex process. The purpose of this update is to review the concept of animal models of spine fusion by summarizing previous models, identifying strengths and deficiencies, reviewing the strategy for selecting a model, and highlighting knowledge gaps suitable for future research. With recent advances in the knowledge regarding gene-specific therapies and the availability of osteoinductive proteins, we have entered a new era of biologic manipulation of bone formation. Animal data, however, are only as applicable as the model from which it is derived, and future animal models must overcome the deficiencies highlighted in this review. A valid animal model will prove essential in studying the use of growth factors for spinal fusion. The ultimate goal is that fusion nonunions will no longer be of clinical concern. PMID- 7997938 TI - Smoking abstinence. Is it necessary before spinal fusion? PMID- 7997939 TI - Isometric maximal and sub-maximal trunk extension at different flexed positions in standing: triaxial torque output and EMG. PMID- 7997940 TI - Laboratory model of lumbar disc protrusion: fissure and fragment. PMID- 7997942 TI - Treatment of IgA nephropathy. PMID- 7997941 TI - IgA nephropathy in children and adults. PMID- 7997946 TI - Involvement of tumor necrosis factor-alpha in glomerular injury. PMID- 7997944 TI - Adhesion molecules in glomerulonephritis. PMID- 7997943 TI - Mechanisms of endothelial cell injury in vasculitis. AB - The aetiology of the primary systemic vasculitides remains obscure. Recent years have seen significant advances in our understanding of inflammation and in particular the role of and interaction between the vascular endothelium, mediators and immune effector cells. This has helped to further elucidate those specific processes relevant to vasculitis which result in endothelial cell damage. In Wegener's granulomatosis and microscopic polyarteritis the evidence favours an autoimmune inflammatory response characterised by specific mediators in which the endothelium is both target and active participant. Current treatment of these disorders with combinations of corticosteroids and cytotoxics is highly effective in inducing remission. However, long-term use of this therapy is potentially toxic and there remains also a significant risk of relapse. It is hoped that increased understanding of the pathogenesis of systemic vasculitis will enable more specific, less toxic and more effective therapies to be defined. Jayne et al. have suggested a beneficial effect of intravenous pooled normal human immunoglobulin (IVIG) in patients with ANCA-positive vasculitis. In vitro studies have shown that IVIG contains antiidiotypic antibodies to ANCA and AECA, capable of inhibiting the binding of these autoantibodies to their autoantigens. In vivo, IVIG may also provide the immunoregulatory elements needed for the idiotype network and control of the autoimmune repertoire. Mathieson et al. successfully used monoclonal antibodies to T cells (Campath-H directed against CDw52) in a patient with ANCA-negative dermal lymphocytic vasculitis. Monoclonal antibodies to CAMs have been used in human renal transplant rejection and reduced the inflammation and proteinuria in animal models of anti-glomerular basement membrane disease. In vasculitis, the therapeutic use of specific anti-CAM antibodies may result from further definition of the role of CAMs. Increased understanding of the pathogenesis of systemic vasculitis is likely to provide the basis for the use of more specific immunotherapies in the future. PMID- 7997947 TI - Renal scarring: a new look at an old problem. PMID- 7997945 TI - Inflammation and glomerular injury. PMID- 7997948 TI - T cell subsets in glomerular diseases. PMID- 7997951 TI - "The power of Texas dentistry." The Conference for Legislative Action Committees of Component Societies of the Texas Dental Association. PMID- 7997950 TI - Experimental IgA nephropathy: factors influencing IgA-immune complex deposition in the glomerulus. PMID- 7997952 TI - The 1993 C.T. Rowland Award orthodontic case report. PMID- 7997949 TI - Immunopathogenesis of experimental IgA nephropathy. PMID- 7997953 TI - Access to dental care from a private practice perspective. PMID- 7997954 TI - Estate planning and asset protection: the new frontier. PMID- 7997955 TI - "I don't want to lose my tooth". PMID- 7997956 TI - Informed consent in Texas. PMID- 7997957 TI - With hopes for a very good death. PMID- 7997958 TI - Guidance from a veteran ethics committee. PMID- 7997959 TI - Regulating death. A discussion of Texas law regarding death and dying. PMID- 7997960 TI - Rx for conflict. Nurse practitioners target independent prescriptive authority in 1995 Texas Legislature. PMID- 7997961 TI - Wheelings and dealings. Physicians push for universal bicycle helmet law in Texas. PMID- 7997962 TI - That day in November. A Dallas physician remembers his experiences at Parkland Memorial Hospital on November 22, 1963. PMID- 7997963 TI - Children at risk for accidental burns from hot tap water. AB - The American Academy of Pediatrics identifies young children at risk for accidental hot tap water (HTW) burns and recommends that HTW temperatures be set no higher than 49 degrees C (120 degrees F). Studies show that a temperature of 52 degrees C (125 degrees F) can cause a full-thickness skin burn in 2 minutes and a temperature of 54 degrees C (130 degrees F) can result in a full-thickness skin burn in 30 seconds. We sought to identify the risk for HTW injury and the knowledge about safety limits at our military installation. Sixty family housing units were selected at random for measurement of HTW temperature by both an electronic thermometer and a mechanical thermometer. Fifty-three (88.3%) and 44 (73.3%) units had temperatures greater than 52 degrees C (125 degrees F) and 54 degrees C (130 degrees F), respectively. We found temperatures that were unsafe at all heater settings. Most parents with children younger than 6 years (51%) were unaware of the danger of HTW to their children. We concluded that children living on our military post were at high risk for serious accidental HTW burns. Moreover, existing qualitative settings are not reliable indicators of safe temperatures. We recommend that health-care providers inform parents about the dangers of HTW burns to children and advise setting maximum HTW temperatures to the 49 degrees C (120 degrees F) recommended by the American Academy of Pediatrics. PMID- 7997964 TI - Antimicrobial resistance of bacterial pathogens at two tertiary-care centers, in Riyadh and Texas. AB - Antimicrobial resistance of bacterial pathogens usually varies from one geographic location to another. During the last 20 years, outbreaks of disease caused by multiresistant bacteria have occurred with higher frequency in developing countries. We investigated the antimicrobial resistance patterns of bacteria isolated in 1992 from two tertiary-care centers, in Riyadh and Texas. Of the 8841 strains used, 5318 were isolated from clinical specimens of patients at King Faisal Specialist Hospital and Research Centre, Riyadh, and 3523 were from Olin E. Teague Veterans Medical Center, Temple, Tex. Members of Enterobacteriaceae at the King Faisal hospital were significantly more resistant to frequently prescribed antimicrobials than were those at the Olin Teague center. Susceptibility to less frequently used agents like ciprofloxacin and ceftazidime was similar at both hospitals. Resistance patterns of Pseudomonas aeruginosa, Haemophilus influenzae, and coagulase-negative staphylococci were similar at both medical centers. The Olin Teague center encountered significantly more methicillin-resistant Staphylococcus aureus and vancomycin-resistant enterococci. PMID- 7997965 TI - School children, as well as physicians, need education about health curricula. PMID- 7997966 TI - School-based primary care links children and youths with private practitioners. PMID- 7997967 TI - Physicians and patients should be involved in Medicaid reform. PMID- 7997968 TI - The hyperreality of clinical ethics: a unitary theory and hermeneutics. AB - Medical ethics nowadays is dominated by a conception of ethics as the application of moral theories and principles. This conception is criticized for its depreciation of the internal morality of medical practice and its narrow view of external morality. This view reflects both a lack of interest in the empirical realities of medicine and a neglect of the socio-cultural value-contexts of medical ethical issues, including the creative development of a broader philosophical framework for a practicable medical ethics. Several alternative approaches and conceptions have been proposed. The unified clinical ethics theory, developed by Graber and Thomasma, is an interesting attempt to synthesize these alternative approaches. It correctly identifies as the crucial problem the present disconnectedness of medical ethics from theoretical philosophy as well as the practice of medicine. In this paper, however, it is argued that the unitary theory should take more serious attention to the hermeneutic character of medicine as well as ethics. This implies that the unitary theory must in fact transform itself into an interpretive clinical ethics theory. The theoretical characteristics and practical consequences of an interpretive theory of medical ethics are discussed in the present paper. PMID- 7997969 TI - Hermeneutical clinical ethics: a commentary. AB - Essays by Thomasma and ten Have recommend hermeneutical clinical ethics. The use Thomasma makes of hermeneutics is not radical enough because it leaves out basic interpretation of clinical practice and focuses narrowly on ethical principles and rules. Ten Have, while failing to notice that the hyperreality of clinical ethics is a feature of all language, rightly distinguishes four characteristic parameters of a thoroughgoing interpretive clinical ethics: experience, attitudes and emotions, community, and ambiguity. Suggestions are made for implementing hermeneutical ethics in clinical teaching. PMID- 7997970 TI - From principles to principals: the new direction in medical ethics. AB - Many alternatives or supplements to "principalism" seek to reconnect medical ethics with the thoughts, feelings, and motivations of the persons directly involved in ethically troublesome situations. This shift of attention, from deeds to doers, from principles to principals, acknowledges the importance of the moral agents involved in the situation-particular practitioners, patients, and families. Taking into account the subjective, lived experience of moral decision making parallels recent efforts in the teaching of medicine to give the patient's subjectivity-his or her personal experience of being sick or disabled epistemological parity with scientific medicine's "objective," biomedically oriented view of the person's sickness or disability. Moreover, the shift from principalism to principals signals a growing realization that ethical problems in the profession of medicine are inseparable from its practice. Philosophers and other humanists working in medicine should resist the temptation to institutionalize a professional role as solver of ethical problems, clarifier of values, or mediator of disputes and work instead to help practitioners practice medicine reflectively. PMID- 7997971 TI - Is medicine hermeneutics all the way down? AB - Several recent publications have suggested that hermeneutics, the method of literary criticism, might prove to be useful in medicine. In this essay I consider this thesis with particular attention to the claim that medicine "is hermeneutics all the way down". After examining an anti-positivist critique of positivist medicine and arguing that hermeneutic interpretation involves a more radical critique of modern medicine, I examine the supposed consequences of hermeneutical universalism: relativism, skepticism and antirealism which further evaluation reveals to be only potential consequences of hermeneutics. A brief discussion of phronesis and of the possible "texts" of medicine concludes the article. PMID- 7997972 TI - United States and Canadian approaches to justice in health care: a comparative analysis of health care systems and values. AB - The purpose of this study is to compare and contrast the basic ethical values underpinning national health care policies in the United States and Canada. We use the framework of ethical theory to name and elaborate ethical values and to facilitate moral reflection about health care reform. Section one describes historical and contemporary social contract theories and clarifies the ethical values associated with them. Sections two and three show that health care debates and health care systems in both countries reflect the values of this tradition; however, each nation interprets the tradition differently. In the U.S., standards of justice for health care are conceived as a voluntary agreement reached by self interested parties. Canadians, by contrast, interpret the same justice tradition as placing greater emphasis on concern for others and for the community. The final section draws out the implications of these differences for future U.S. and Canadian health care reforms. PMID- 7997973 TI - Philosophy and its role in medicine: inaugurating a new section. PMID- 7997974 TI - Clinical ethics as medical hermeneutics. AB - There are several branches of ethics. Clinical ethics, the one closest to medical decisionmaking, can be seen as a branch of medicine itself. In this view, clinical ethics is a unitary hermeneutics. Its rule is a guideline for unifying other theories of ethics in conjunction with the clinical context. Put another way, clinical ethics interprets the clinical situation in light of a balance of other values that, while guiding the decisionmaking process, also contributes to the very weighting of those values. The case itself originates ideas, not only about which value ought to predominate in its resolution, but also provides the origin of clinical rules that can be used in other cases. These are interpretive rules. Some examples of these rules are presented as well. PMID- 7997975 TI - Purification of the plasmin receptor from human carcinoma cells and comparison to alpha-enolase. AB - We have characterized a receptor for plasmin (Pli-R) from a human tumor cell line, MCF7MF. The Pli-R was purified from a MCF7 0.1% Triton X-100 solubilisate by affinity chromatography. A protein of 55-60 kDa was obtained, which bound plasminogen and plasmin specifically. Chemical cross-linking of M(r) 90 kDa [125I]-Pli to the surface of MCF7 cells with DSP results in the formation of a labelled complex of M(r) 145 kDa, suggesting a M(r) of 55-60 kDa for the receptor. Comparing Pli-R with alpha-enolase (a candidate for plasminogen receptor in U937 cells) we have found a high homology between both proteins, but not an identity. PMID- 7997976 TI - Calcium threshold in human plasma clotting kinetics. AB - In vitro clotting kinetics of citrate human blood plasma under its titration with calcium ions are studied. Contact activation (Factor XIa + plasma kallikrein) is shown to be independent of calcium while non-linear growth of thrombin concentration is demonstrated at calcium concentrations higher than 0.25 mM under conditions of contact activation caused by quartz walls of the measuring cell. Thrombin generation kinetics are well fitted with an exponential function. Power index of the exponential function steeply rises as calcium concentration increases from 0.25 to 0.5 mM and reaches plateau at higher concentrations. At free calcium concentrations under 0.25 mM thrombin level does not grow remaining lower than 30 pM. So, blood coagulation system behaves in a threshold manner under calcium concentration changes. The threshold concentration of free calcium is equal to 0.25 +/- 0.05 mM. PMID- 7997977 TI - Heterogeneity of the APC-resistance phenomenon. AB - We developed an amidolytic assay for the determination of APC-resistance by inhibition of factor Xa (F Xa) generation, expecting it to be a result of factor VIIIa (F VIIIa) inactivation. Thirty-nine samples were tested with the proposed assay and compared to an APTT-based assay performed using the APC-resistance kit (Chromogenix, Molndal, Sweden). In both assays APC was added at the last stage of the reaction together with CaCl2. The response to APC was calculated as a ratio of absorbances (or of clotting times) of a sample tested with or without APC and as the amount of F VIII activity generated in the presence of APC. An APC-ratio less than 2.0 and residual F VIII activity over 55% indicated APC-resistance. The results demonstrated that APC-response was heterogenic and dependent on the assay used for the determination. Only 1/3 of the tested samples were resistant in both APTT-based and in amidolytic assays. A number of samples developed an adequate decrease in F VIII activity, but the APC-resistance was still registered by the APTT-based assay. Other samples had a sufficient APC-response in APTT-based assay, in spite of diminished inactivation of F VIIIa. The obtained data presented the response to APC as a complex process with a chain of reactions. It indicated that poor degradation of coagulation factors may not be sufficient for its development. PMID- 7997978 TI - Parallel determination of von Willebrand factor--Ristocetin and Botrocetin cofactors. AB - The quantitative determinations of von Willebrand Factor (vWF)-Ristocetin cofactor (vWF:RCof) and the Botrocetin cofactor (vWF:BCof) are important parameters for the diagnosis of von Willebrand's disease. These cofactors are usually determined in a platelet aggregometer using separate platelet reagents and assay protocols. We describe a method for the preparation of platelets made from outdated platelet concentrates and fixed with paraformaldehyde which agglutinate to ristocetin and to botrocetin. The platelet agglutination assay protocol has been simplified such that the same aggregometer instrument, platelet reagent, buffers and the reaction volumes can be used for parallel determination of vWF:RCof and vWF:BCof. PMID- 7997979 TI - A new method for measurement of plasma concentration of orally active glycoprotein IIb/IIIa antagonists. AB - A bioassay for determining concentrations of antiplatelet compounds in plasma or aqueous solution has been developed. The method uses an aliquot of plasma from treated animals to inhibit collagen-induced platelet aggregation in pooled platelet-rich plasma (PRP) obtained from donor dogs. The concentration in plasma from treated animals was estimated using a standard curve of inhibition established using plasma from untreated animals which had been spiked with known amounts of compound. For independent validation, plasma concentrations of certain compounds were determined in identical dog plasma samples by both bioassay and HPLC. Results from the two methods were concordant. The bioassay provides an accurate and sensitive method for measuring antiplatelet activity without the need for extraction of plasma samples and may be used to measure activity in any solution which is compatible with PRP. This assay is routinely used to provide an estimate of absorption of prodrugs and systemic conversion to active compound after oral dosing. Some of the compounds of interest are ester-acid pairs with the inactive ester prodrug being cleaved to the active acid following administration. Compounds were administered orally (ester) or IV (acid) and blood samples were taken periodically for 24 hours. Plasma concentration of active moiety was determined for each time point and the area under the curve (AUC) of concentration vs. time was calculated. Comparing the AUCs for oral and IV routes of administration yielded the Oral Systemic Activity (OSA), a measure of active compound available after oral dosing. PMID- 7997980 TI - Thrombin generation in patients undergoing carotid endarterectomy: implications in acute vessel wall closure and antithrombotic therapy. AB - We determined the extent and duration of activation of coagulation during the first 24 hours after carotid endarterectomy. Serial blood samples were collected before, during and after surgery from 10 patients with severe stenosis (> 70%) undergoing carotid endarterectomy with heparinization. Platelet poor plasmas prepared from these samples, were analysed for activated prothrombin fragment F1 + 2 and thrombin-antithrombin III (TAT) levels, using commercially available ELISA kits. F1 + 2 and TATs were measured as indices of thrombin generation and inhibition respectively. Baseline F1 + 2 and TAT levels were 1.19 +/- 0.27 nMol/ml and 17 +/- 10 pMol/ml, respectively. Neither the F1 + 2 nor TAT level increased during surgery at a time when the patients were heparinized. However, both the F1 + 2 and TAT levels increased significantly within 3 hours after surgery and after the heparin had been neutralized with protamine, (p < 0.01). Moreover, both the F1 + 2 and TAT levels remained elevated in 75% of the patients for at least 24 hours, p < 0.01. We conclude that i) thrombin generation is significant post surgery in patients undergoing carotid endarterectomy despite their receiving heparin during surgery; ii) heparin may not be the ideal anticoagulant for carotid endarterectomy; and iii) persistent thrombin generation may contribute to early post-endarterectomy ischemic events. PMID- 7997981 TI - Effect of gamma carboxylation on prothrombinase inhibitory activity of catalytically inactive factor XA. AB - Recombinant catalytically inactive factor Xa (factor rXai) is capable of assembly into inactive prothrombinase complexes, thus serving as a competitive inhibitor (Ki = 0.3nM) of active factor Xa. In order to study the role of gamma carboxylation in prothrombinase complex assembly, we have prepared differentially gamma carboxylated factor rXai and have measured the activities of these proteins in prothrombinase complex inhibition and in extension of plasma clotting. A factor rXai preparation containing 8 out of a possible maximum of 11 g carboxyglutamic acid (GLA) residues was found to be as active as chemically inactivated plasma factor Xa which was fully gamma carboxylated. Loss of a single additional g carboxyglutamic acid in the recombinant protein, however lead to a marked loss in activity. Factor rXai preparation with 8 GLA residues is also detected by a monoclonal antibody specific for a GLA dependent epitope. Thus assembly of the factor Va/Xa complex on phospholipid membranes does not require the presence of all of the g carboxyglutamic acid residues present in the plasma protein. PMID- 7997982 TI - Complement-mediated permeabilization of platelets by monoclonal antibodies to CD9: inhibition by leupeptin, and effects on the GP Ib-actin-binding protein system. AB - Two monoclonal antibodies to CD9 of the IgM and IgG2a categories (FN 52 and FN 99), reproducibly induced platelet alterations in platelet-rich plasma by activation of the complement system with membrane incorporation of the pore forming C5b-9 complex. The permeabilization could be monitored by measurements of extracellular ATP and observed as a shape change followed by an increase in light transmission in the aggregometer, and was associated with formation of tiny platelet aggregates. This could be accomplished by only minor lysis observed as extracellular lactate dehydrogenase (LDH). When leupeptin was added prior to, or immediately after the antibody, a total inhibition of the platelet alterations could be obtained. When added soon after the shape change, leupeptin had little effect on the liberation of ATP. However, whereas the ability of the platelets to become agglutinated by ristocetin was lost during the complement-mediated platelet alterations, addition of leupeptin immediately after the shape change, prevented this loss. The lost ability of the permeabilized platelets to undergo ristocetin-induced agglutination is not ascribed to degradation of GP Ib as this was relatively little affected in these studies as compared to the actin-binding protein (ABP) which was profoundly degraded. This protein represents a link between GP Ib and the submembraneous cytoskeleton, and the inhibition of its degradation by leupeptin, was clearly demonstrated. Experiments with digitonin induced permeabilization showed that leupeptin did not inhibit permeabilization as such, but it did prevent the loss of ristocetin-induced agglutination even with this inducer. PMID- 7997983 TI - Pharmacokinetics of tinzaparin (Logiparin)--a low molecular weight heparin--after single and repeated intravenous administration in rats. AB - After a single and repeated i.v. injections of 1 mg/kg 3H-radiolabelled tinzaparin once daily to rats for 7, 14, and 21 days, drug-related radioactivity in plasma, tissues, urine and faeces was measured by use of liquid scintillation counting. The decay in plasma could be described by a three-compartment model with half-lives of the two distributive phases and the terminal elimination phase of 15 min, 90 min, and 37 hrs, respectively. The peak plasma concentration did not change during repeated dosing, as opposed to the trough concentration which increased 3 fold. The decay in tissues was significantly different from that in plasma, and showed less fluctuations. Drug-related radioactivity accumulated gradually with repeated dosing, reaching accumulation ratios between 5 and 9, when based on trough concentrations. Slow elimination was observed from tissues, and significant amounts were still present 14 days after discontinuation of the repeated dosing. In the liver, the concentrations were almost constant during a dosing interval. After a single injection, 86% and 4% of the administered radioactive dose were excreted in urine and faeces over 7 days, respectively, the majority being recovered during the first 24 hrs, demonstrating that the major route of elimination was by renal excretion. The molecular mass distribution of radioactivity in urine was similar but not identical to the injected test substance. It was shifted slightly towards lower molecular mass and had no anti factor Xa activity, suggesting that the heparin was either inactivated, presumably by desulphation, or that the antithrombin binding portion of the drug was cleared through a different route. PMID- 7997984 TI - Preferential use of dilutions of single sera than mixture of sera to standardize the quantitation of anticardiolipin antibodies. AB - The aim of this study was to compare four house standards coming from two University Hospital laboratories with the standards provided by the Antiphospholipid Standardization Laboratory (ASL) in order to quantify anticardiolipin antibodies. Using two different plates and two different buffered protein solutions, slopes from the serial dilutions of each of the four house standards were found comparable. In contrast different slopes were obtained when using the ASL standards which consist of a mixture of sera. Our results indicate that dilutions of single sera are more suitable than mixture of sera when quantification of anticardiolipin antibodies is required. PMID- 7997985 TI - Plasminogen activator inhibitor is elevated in plasma and diminished in platelets in patients with diabetes mellitus. PMID- 7997986 TI - Parallel line bioassay or single-point calibration for the establishment of reference ranges. PMID- 7997988 TI - [Paraneoplastic syndromes--are they significant?]. PMID- 7997987 TI - Platelet hyperfunction exists in both acute non-haemorrhagic and haemorrhagic stroke. PMID- 7997989 TI - [Treatment of suicide attempters in a somatic department]. PMID- 7997990 TI - [Why and how should the clinical behavior of physicians be changed?]. PMID- 7997991 TI - [Treatment of suicide attempters in a somatic hospital. Is psychosocial support offered in addition to somatic treatment?]. AB - The study examined whether patients admitted to a somatic hospital following an attempted suicide were offered psycho-social assessment and care in addition to somatic treatment. The medical records of 81 patients involving a total of 90 admissions following a suicide attempt during a period of one year were scrutinized. 1/3 of the medical records showed no evidence of a talk between the patient and a health professional about the attempted suicide. Patients staying in hospital for less than 24 hours were less likely to have had such a talk than those who stayed longer. No other variable, not even the patients' negative attitude towards hospital care was associated with the talk variable. Without an anamnesis where suicide-related themes are approached the health professional can neither judge the danger of a new suicide attempt nor the need for psycho-social help. PMID- 7997992 TI - [Dermatomyositis and cancer. A retrospective study]. AB - In a retrospective study, the files of 19 patients with dermatomyositis examined at our departments from 1970 to 1993 were reviewed. The parameters studied were age, sex, muscle enzyme values, muscle biopsies, electromyographical findings and interval from onset of dermatomyositis until first visit to the department. Out of 19 patients with dermatomyositis, 18 were adults and in nine of these the condition was associated with cancer (three out of three men, six out of 15 women). Electromyographical findings were pathological in 17 investigated patients and myositis was indicated in 13 out of 15 biopsies. Muscle enzyme values were elevated in seven out of nine patients with cancer and in three out of nine without. Out of five patients with dysphagia, four patients had cancer. The risk of cancer is increased in patients with dermatomyositis. Factors indicating a poor prognosis regarding the association between dermatomyositis and cancer in our study were old age, male sex and dysphagia. PMID- 7997993 TI - [Atopic eczema]. AB - Atopic eczema is one of the most common skin diseases of our time, and has commonly been regarded, without further proof, as caused by allergic factors. Although allergy may be involved in some cases, it is probably no more than an exacerbating factor and not the underlying cause. This has important implications for diagnosis and therapy. In recent years the interest has centred on the functional aspects of the skin barrier, with emphasis on lipid constituents in stratum corneum. The authors present some new data on the barrier function which are relevant to diagnosis and therapy. PMID- 7997994 TI - [Rhabdomyolysis in carnitine palmitoyltransferase deficiency]. AB - A 45 year old man had had recurrent rhabdomyolytic episodes from the age of 16 following prolonged exercise or infection. During one episode he developed respiratory and renal failure, but recovered completely. Biochemical investigation of muscle biopsy showed deficiency of carnitine palmityl transferase (CPT), an enzyme involved in the beta-oxidation of fat metabolism. PMID- 7997996 TI - [Primary care physician's evaluation of psychiatric outpatient clinics]. AB - In order to study to what degree physicians responsible for primary care are satisfied with the service provided by psychiatric outpatient clinics, we selected a catchment area of 240,000 inhabitants in Rogaland county, Norway. This area is served by 154 primary care physicians and two psychiatric outpatient clinics staffed with a total of 19 psychiatrists, psychologists, social workers and nurses. 90% of the primary care doctors answered a questionnaire on their degree of satisfaction with the psychiatric outpatient unit. 63% reported needing more and better service. 60% had patients who should have been referred, but were not, and 44% indicated that, in their experience, the patients were treated by professions other than the desired ones. 60% reported that the greatest need was for evaluation of patients, and 38% wanted more long-term treatment. The physicians found refusal of referrals unacceptable without having an opportunity to discuss the case first. Waiting lists could be accepted, but preferably after advice had been given on treatment. PMID- 7997997 TI - [Exchange of medical students]. PMID- 7997998 TI - [Methods for quality assurance in general practice]. PMID- 7997995 TI - [Better knowledge about HLA-molecules gives new therapeutic options]. AB - HLA molecules play a central role in the initiation and perpetuation of immune responses. Our knowledge about the structure and function of these molecules has increased considerably in the last few years. This has opened up for new therapeutic options in auto-immune diseases and cancer, and has greatly improved the outcome of organ transplantation. In this review, the author presents some of the new possibilities of manipulating immune responses via the HLA molecules. PMID- 7998000 TI - [Digitalis in the treatment of heart failure]. PMID- 7997999 TI - [Quality of health care]. PMID- 7998001 TI - [Revenge of the microbe]. PMID- 7998002 TI - [Treatment of hypertension anno 1994]. PMID- 7998003 TI - ["Clarification" before punishment--a medical matter]. PMID- 7998004 TI - [Training in practical surgery]. PMID- 7998005 TI - [Is there a regional hospital in health district no.1?]. PMID- 7998006 TI - [Clinical use of bone mineral measurements]. PMID- 7998007 TI - [Interventional radiology--with imaging technology for solution of somatic problems]. PMID- 7998008 TI - [Splenectomy--vaccination is necessary!]. PMID- 7998009 TI - [Splenectomy and pneumococcal vaccine. How to follow-up?]. AB - The authors describe the case of an otherwise healthy man who died from pneumococcal septicemia 18 years after having undergone splenectomy. It is widely accepted that splenectomized patients run increased risk of serious bacterial infections. Meningitis and septicemia caused by encapsulated organisms, especially Streptococcus pneumoniae, are most important in this respect, with a reported mortality of 30-60%. Since 1977, splenectomized patients have been offered pneumococcal vaccine as a routine, but persons who was splenectomized before 1977 are not identified, and run an unknown risk of serious infectious disease. Possible approaches to this problem of identification are discussed. PMID- 7998011 TI - [The pitting function of the spleen visualized in a patient]. AB - A patient with sideroblastic anemia was splenectomized. After the splenectomy numerous inclusions were present in the erythrocytes, whereas there were almost none before the splenectomy. PMID- 7998010 TI - [High incidence and mortality of systemic pneumococcal disease among persons without spleen]. AB - We surveyed 472 cases of culture-confirmed systemic pneumococcal disease that were reported to the Norwegian Notification System for Infectious Diseases during a 12-month period in 1992-93. The clinicians in charge of the patients filled in a questionnaire providing information on underlying disease and outcome for 461 (98%) of the patients. Eight of these patients were splenectomized; all of them more than ten years before. Four died, two survived but had serious sequelae, and two survived without obvious sequelae upon discharge from hospital. Using a rough estimate of the prevalence of unvaccinated splenectomized persons in Norway, we estimate that this group, compared to the normal population, has a relative risk of 25 of developing systemic pneumococcal disease and a relative risk of 75 of dying from pneumococcal disease. The serotype of the pneumococcal strain that caused the disease was determined for seven of the eight patients. All serotypes were represented in the 23-valent pneumococcal polysaccharide vaccine. We strongly recommend that doctors trace and vaccinate splenectomized individuals. PMID- 7998012 TI - [Polymyalgia rheumatica and temporal arteritis. New aspects of diagnosis, treatment, prognosis and risk of cancer]. AB - The incidence of polymyalgia rheumatica and temporal arteritis is increasing, mainly in elderly people. The risk of cancer during a lifetime is high in patients with positive biopsy of the temporal artery, but polymyalgia rheumatica and temporal arteritis are not to be considered as paraneoplastic syndromes. Temporal arteritis can appear in patients under treatment for polymyalgia rheumatica, and polymyalgia rheumatica can be accompanied by arthritis. Various new aspects of diagnoses and treatment are discussed. PMID- 7998013 TI - [Peptide modulation in vascular headache]. AB - This article reviews recent developments in the field of vasoactive peptides in relation to certain types of headache. The equilibrium existing in the brain between contraction and dilatation of blood vessels is controlled by, among other factors, vasoactive peptides. Several of these have been discovered only recently and constitute a rapidly expanding field of research with exciting perspectives. Cranial blood vessels are innervated by sympathetic, parasympathetic and sensory nerve fibres, all of which contain certain vasoactive peptides as co transmitters. Others, like endothelin, can be produced by the endothelium. There is evidence to suggest that vasoactive peptides of the trigeminovascular system are liberated in response to abnormal constriction of cranial blood vessels and contribute to headache. New drug therapies based on the activity of such substances are now being developed. PMID- 7998014 TI - [Biological pollution of indoor air]. AB - Biological pollution of indoor air can consist of viruses, bacteria, fungi, fungal spores, mites, dander and metabolic products from the microorganisms. The occurrence of such pollution can occasionally cause building-related adverse health effects. Allergens produced by house dust mites and in the dander of furred domestic animals are generally regarded to be among the most important causes of disease episodes in atopic individuals. Bacteria and fungi as such cause building-related disease more rarely. An exception is respiratory infections caused by Legionella bacteria. Other possible health effects of biological indoor air pollution have been suggested, but the data are inconclusive. PMID- 7998015 TI - [The "umbrella closure" of the ductus arteriosus]. AB - The technical details of the method are outlined, and the Norwegian experience reported: From September 1988 to January 1994 we attempted to close open ducts with the Rashkind technique in 26 patients. Two ducts were too small to accept the device, and in one case the implanted device could not be released. This patient was referred to surgery. In the remaining 23 patients the device was left in place. The mean X-ray fluoroscopy time was 15 minutes. No complications occurred. In eight patients (35%) a residual shunt could be detected by ultrasonic Doppler technique, but in seven of them haemodynamical significance was lacking. The umbrella method is a good alternative to traditional treatment. PMID- 7998016 TI - [Catheter treatment of renal artery stenoses]. AB - Percutaneous transluminal renal artery angioplasty (PTRA) is an alternative to treatment with drugs and surgery for renovascular hypertension and uremia. The procedure is technically successful in more than 90% of the patients. Renovascular hypertension is cured or improved in nearly 2/3 of the patients. Uremia is cured in 50%, and in another third the kidney function is stabilized. The frequency of restenosis is high, especially for ostial lesions. Therefore, clinical and angiographic follow-up is recommended, so as to redilate when restenosis is present. Introduction of stents probably reduces the frequency of restenosis in the ostial lesions. PMID- 7998017 TI - [All persons without spleen should be given pneumococcal vaccine]. AB - Splenectomized individuals run increased risk of developing overwhelming septicemia from encapsulated bacteria, especially Streptococcus pneumoniae. Polyvalent pneumococcal polysaccharide vaccine should be given to all splenectomized individuals above two years of age. Antipneumococcal antibody levels should be measured three to five years after the first vaccination, and persons with low antibody levels should be revaccinated. Splenectomized persons may be given a supply of penicillin V to enable them to start therapy while avaiting medical attention. PMID- 7998018 TI - [Prioritization of fertilization in vitro--a systematic analysis]. AB - Who should be offered medically assisted conception treatment within a public health care system? This article discusses medical and ethical selection criteria in relation to general political guidelines for prioritization. Our tentative conclusion is that it is possible to differentiate between groups of patients according to disease criteria, the severity of disease, medical efficacy and cost efficiency. We note that there is a great need for data to enable well-founded decisions when prioritizing applicants for in vitro fertilization within a public health care system. PMID- 7998019 TI - [Quality of nursing homes]. PMID- 7998020 TI - [Mass vaccination against tuberculosis--do we need it in Norway?]. PMID- 7998021 TI - [What stone age?]. PMID- 7998022 TI - [Working--a public disease]. PMID- 7998023 TI - [Social class--a disappearing dimension?]. PMID- 7998024 TI - [Documentation requirements--is doubt good for physicians?]. PMID- 7998025 TI - [Rheumatic fever in Norway--we need a better overview]. PMID- 7998026 TI - [Somatostatin as a help in fistula problems]. PMID- 7998027 TI - [Treatment of hypersecretory ileostomy, gastrostomy and fistula of the small intestine with the somatostatin analog octreotide]. AB - Hypersecretory stomas or fistulas are disabling conditions for the patients and a therapeutic challenge to the surgeons. Octreotide treatment is reported to reduce stoma output and the need for intravenous supplements. Octreotide treatment also reduces social disability due to postprandial hypersecretion causing frequent changes of stoma systems. Two patients with high output stomas and one patient with high output ileocutaneous fistula were treated with the somatostatin analogue octreotide. Reductions in stoma or fistula output from 48 to 62% were observed. PMID- 7998028 TI - [Risk of AIDS in the Oslo HIV-cohort study. A comparison between homosexual men, intravenous addicts and heterosexual persons]. AB - In order to study differences in risk of the development of AIDS in different groups of HIV infected subjects, 151 homosexual men, 110 intravenous drug users (IVDUs) and 36 heterosexually infected persons without major signs of HIV infection at entry to the study were enrolled in a cohort study. The mean follow up time was 35 months. At the end of follow-up 40 subjects (13%) were diagnosed as having AIDS. This represented 20% (31/151) of the homosexual men, 7% (8/110) of the IVDUs and 3% (1/36) of the heterosexual subjects. The probability of being AIDS-free 36 months after entering the study was 0.88 (0.84-0.92, 95% CI) for the total study population, 0.83 (0.77-0.90) for the homosexual men, 0.92 (0.86-0.99) for IVDUs and 0.93 (0.91-1.0) for heterosexual subjects (p < 0.05, log rank test). In a Cox regression analysis, adjusting for CD4+ cell count at study entry, the relative risk of AIDS progression was 2.4 (1.1-5.2) for homosexual men and 0.3 (0.04-2.4) for heterosexual subjects, compared with IVDUs. The results demonstrate a higher risk of AIDS for homosexual men during the follow-up period. PMID- 7998029 TI - [Is blood pressure treatment as effective in a population setting as in controlled studies?]. AB - Baseline (1974-76) and repeat (1977-81) cardiovascular screenings of 21,314 men aged 35-49 years brought to light 840 men who had started treatment between screenings. These were compared with men who had remained untreated. The effects of treatment on blood pressure were small, and normal target blood pressures rare. At pretreatment blood pressure up to systolic 184 mm Hg, and in most risk strata, both total mortality and cardiovascular mortality were higher among the men on treatment. This study shows an adverse effect of treatment in a population setting, particularly at low pretreatment blood pressure, and if blood pressure increases upon treatment. PMID- 7998030 TI - [Frontal epileptic seizures]. AB - Video-telemetry, with EEG recordings from intracranial electrodes, has been used for the past 15 years at the National Center for Epilepsy to identify candidates for epilepsy surgery. The recordings have been a useful tool for correlating neuroanatomy and ictal, epileptic symptoms. The authors describe the most characteristic clinical symptoms and electroencephalographic findings in seizures deriving from the frontal lobe. An attempt is made to subclassify seizures deriving from different parts of the frontal lobe. Frontal lobe seizures are illustrated by three case histories. PMID- 7998031 TI - [Vigabatrin--a new antiepileptic agent]. AB - The new antiepileptic drug vigabatrin acts by preventing degradation of the inhibitory neurotransmitter GABA (gammaaminobutyric acid). This appears to decrease propagation of abnormal hypersynchronous discharges, thus reducing seizure activity. In an open study in 46 patients with intractable epilepsy, supplementary therapy with vigabatrin reduced seizure by at least 50% in 15 patients. Three patients became seizure-free. The best effect of vigabatrin is seen in patients with partial epilepsy. Tiredness and irritability were the most frequently reported side effects, but these were usually mild and transient. PMID- 7998032 TI - [Percutaneous lumbar diskectomy]. AB - At the Department of Neurosurgery in Trondheim, 17 patients with low backpain and sciatica have been operated upon using percutaneous lumbal discectomy. The procedure was carried out under local anaesthesia and all patients were discharged on the first day after operation. Seven patients recovered completely, four patients showed some improvement, and six patients showed no change. All the patients who reported a complete recovery experienced pre-operative stress dependent radicular pain with mild neurological deficits. In contrast, the group of patients who showed no change suffered more constant pain, with a diffuse localization and no neurological deficits. It is important to make a thorough pre operative evaluation of these patients, and correct selection is essential to achieve a good result. PMID- 7998033 TI - [Percutaneous automated lumbar nucleotomy. Patient selection, practical performance and clinical results]. AB - Percutaneous nucleotomy is designed to treat small and medium-sized contained disk hernias. It is offered to patients who have not responded to conservative treatment for three months or more. The nucleotomy procedure is well tolerated by a majority of patients and the rate of complications is low. The patients can be treated as out-patients. Among a total material of 130 patients, a primary good response to the treatment was observed in 81 (62%). However, owing to recurrencies the success rate had fallen to 52% at 12-39 months (mean 22 months) after nucleotomy. In selected patients with symptoms from one disk level only, and with no evidence of spinal stenosis, or of osteophyte formation or a narrowing of the disk space by more than 25%, the results were better. Here the success rate was 61% (70% in males and 50% in females). PMID- 7998034 TI - [Treatment of varicocele]. AB - Varicocele may cause scrotal pain and swelling, and may be associated with retardation of testicular growth, impaired sperm quality and infertility. Imaging methods may reveal subclinical varicocele. The condition may be treated with high or low ligation of the testicular veins or occlusion via catheter. The occluding material can consist of metal coils or various liquids such as sclerosing agents, glue or heated contrast medium. Good results are reported for clinical symptoms and sperm quality, while the effect on pregnancy rates varies considerably. The rate of complications is low in large series. PMID- 7998035 TI - [Rheumatic fever--does it exist in Norway today?]. AB - During the last 30 years, acute rheumatic fever has been a curiosity in Norway, and only five cases have been reported to MSIS (National Notification System for Infectious Diseases, Norway) in the 1990s. Even so, during the period 1990 to 1992 99 patients were discharged from Norwegian hospitals with the diagnosis acute rheumatic fever. Could the increase in the number of group A-streptococci in the last years have led to a corresponding increase in the incidence of acute rheumatic fever? If so, could such an increase have escaped our attention? We present an updated review of acute rheumatic fever and the case of a young soldier. PMID- 7998037 TI - [Are the new antidepressive agents as effective as the tricyclic antidepressants?]. PMID- 7998036 TI - [Follow-up of persons on long-term sick-leave. A cohort study in the city of Moss]. AB - Follow-up of people on long-term sickness leave has been a priority for central and local authorities for a number of years. In this study we have followed a cohort of such people from the city of Moss. We wanted to find out how many returned to work, and who these were. The cohort consisted of 1,975 persons. Median age was 45 years (25-75 percentile: 35-54 years). 55% were women. Median follow-up time was two years and four months. Incidence of long-term sickness leave (more than eight weeks off sick) was 4.2 per month per 1,000 persons between 16 and 66 years of age. Less than half (47%) of those who had been off sick for more than eight weeks were working at follow-up. Few people were recruited to active rehabilitation programmes; for instance new education and on the-job training. Age, especially from 45 years and upwards, many earlier sickness leaves and diagnosis (persons with psychiatric and other diagnoses did worst) influenced the result towards inactivity. When tested by multivariate analysis these variables explained little of the total variation in re-entry to the job market. A separate study of a random sample who were offered more time and indepth counselling showed no effect on job status at follow-up. Most probably, the success or lack of success are dominated by two factors which we could not measure directly; the seriousness of the medical condition and the climate on the labour market. PMID- 7998038 TI - [Coronary heart disease in the age of technology]. PMID- 7998039 TI - [Prevention of cardiovascular diseases--easier to say than to do]. PMID- 7998040 TI - [It is the results that give the answer, but how should the results be measured?]. PMID- 7998041 TI - [Sumatriptan and general practice]. PMID- 7998042 TI - [Should the used pacemakers be reimplanted?]. PMID- 7998043 TI - [Reuse of implanted pacemakers]. AB - One specific institution reports 310 cases of reuse of pacemakers from 1974 to 1993. 111 were obtained after replacement, and 199 after the death of the first user. The average duration of the primary implant was 12 months (0-53 months). 177 functioned up to time of death, 43 months (0-177 months). In 107 cases the cause of death was unrelated to use of a pacemaker, was unknown in 61, and was sudden in 9 patients. 64 pacemakers were replaced, 14 because of infections or skin erosions. The causes of death and the prevalence and indications for generator replacement coincided with those in our population of new pacemaker users in 1988-93. CONCLUSION: Pacemaker re-use in our hospital is safe and cost effective. PMID- 7998045 TI - [Criteria of general practitioners on the high risk factors for cardiovascular diseases. Information from health survey cards of 40-year old persons in Telemark 1992]. AB - After a health survey of men and women aged 40-42 in Telemark county in 1992, a total of 539 persons were recommended to consult their general practitioner. The physicians returned survey cards for 322 persons, 60% of those recommended, to the National Health Screening Service. A total of 282 persons had consulted the doctor. Non-pharmacological treatment was offered to 93% of the men and 78% of the women. About 10% had either a new diagnosis, a new medication, or were referred to a hospital or an out-patient clinic. The lack of returned survey cards for 40% of the persons who were recommended a consultation is a challenge for the National Health Screening Service to improve communication with general practitioners. PMID- 7998044 TI - [Endarterectomy of left coronary arteries. An angiographic follow-up study]. AB - From January 1989 to December 1993, 25 patients underwent endarterectomy on the left coronary artery system. Eight of the patients had concurrent endarterectomy of the right coronary artery. The operative mortality consisted of one high-risk patient who died from an intraoperative myocardial infarction. Two patients developed non-fatal perioperative infarction. The follow-up period averaged 27 months (range 4-58 months). At follow-up one patient was lost for evaluation owing to unexpected sudden death, no patients had experienced myocardial infarction, 17 patients (74%) were free of angina, two patients were in NYHA class I and four in NYHA class II. All patients showed an improvement in relation to their preoperative condition. Two asymptomatic patients refused recatheterization, while 21 patients had a control angiographic study. 25 of 34 grafts to endarterectomized vessels were open (patency 74%) compared with 41 of 45 grafts to non-endarterectomized arteries (patency 91%). We find the angiographic and functional results acceptable and they should be acknowledged with reference to patients with diffuse distal coronary artery disease, many of whom would otherwise be considered inoperable. PMID- 7998046 TI - [Sumatriptan in the treatment of migraine in general practice]. AB - Approximately 5% of the adult Norwegian population suffer from migraine. Sumatriptan is a new anti-migraine drug which has been shown in clinical studies to be efficacious in up to 80% of attacks treated. These early clinical studies have all been carried out at specialist centres and the present study was planned to see if migraine patients treated by general practitioners would also benefit from this new therapy. This placebo controlled, randomized, double blind study was carried out by 50 general practitioners and two neurologists, and included 294 patients. A total of 1,485 migraine attacks were treated. The results show that Sumatriptan is equally efficacious and well tolerated when used to treat patients in general practice as at specialist clinics. Sumatriptan was efficacious in relieving pain and other migraine symptoms in 76% of the migraine attacks treated, while placebo had the desired effect in 29% of attacks. PMID- 7998048 TI - [Atrial septal aneurysm and cerebrovascular diseases]. AB - Atrial septal aneurysm has a prevalence of 1% in the general population. A case is presented where a clinically healthy man had three cerebellar ischemic events on the basis of an atrial septal aneurysm. The literature on the subject is reviewed, and the importance of transoesophageal echocardiography is emphasized. PMID- 7998047 TI - [Lisinopril and nifedipine have neutral effects on lipids]. AB - In a randomized, double blind, parallel-group, multicentre study in Norway, 97 patients with mild to moderate hypertension (mean blood pressure 159/104 mm Hg) were treated with either lisinopril 10-40 mg or nifedipine 20-80 mg and the effects on blood lipids were evaluated. Complete results of laboratory analyses are given for 80 patients. After a 4 week run-in and placebo period, antihypertensive treatment was given for the next 10 weeks. During treatment with lisinopril the changes in lipids were +2.1% for total cholesterol, +0.7% for HDL cholesterol, +3.8% for triglycerides and -6.1% for ratio HDL/cholesterol-HDL. For nifedipine the corresponding values were -2.4% for cholesterol, -5.8% for HDL cholesterol, +8.0% for triglycerides and +3.2% for ratio. None of these changes was statistically significant. Both lisinopril and nifedipine lowered the blood pressure significantly, 18.1/12.0 mm Hg with lisonopril (p < 0.01 for both systolic and diastolic pressure) and 8.0/8.5 mm Hg with nifedipine (p < 0.01 for both respectively). Both drugs were well tolerated. In conclusion, neither lisinopril nor nifedipine had any negative impact on lipid levels. PMID- 7998049 TI - [Intracoronary stents. Experience from the Feiring clinic]. AB - There are two major problems connected to percutaneous transluminal coronary angioplasty (PTCA): acute closure of the vessel during the procedure and a high rate of late restenosis. Deployment of intracoronary stents has emerged as a procedure that can counteract these difficulties. At the Feiring Clinic 158 patients were treated with intracoronary stents in 1992 and 1993. In 87% of the patients no in-hospital cardiac events occurred. The overall mortality rate was 1.8%. Thrombosis of the stent occurred in 5.7% of the patients and acute myocardial infarction in 5.1%. Emergency bypass operation was performed in 5.1%. The most important predictor for clinical success was a good angiographic appearance after deployment of stent. It is concluded that stent deployment has improved the immediate outcome of a complicated PTCA procedure, and it is likely that it also will reduce the rate of restenosis. PMID- 7998050 TI - [Catheter therapy of coronary disease]. AB - Percutaneous transluminal coronary angioplasty (PTCA) with balloon catheters is a well established invasive treatment for coronary artery disease. The high frequency of restenosis has promoted the development of new catheters, with different techniques for removing the plaques from the coronary arteries. Until now the rate of restenosis using balloon angioplasty and new atherectomy catheters has not declined. Our experience of these techniques is discussed and compared with the experiences described in the literature. The use of stents seems to be a major step forward, leading to fewer restenoses and emergency bypass operations. PMID- 7998051 TI - [Local intraarterial thrombolysis]. AB - The treatment of acute and subacute arterial occlusions poses a difficult clinical problem. Local intra-arterial thrombolysis can be a useful therapeutic alternative. The most commonly used thrombolytic agents are considered. In the treatment of artery or graft occlusions in the lower extremities, the best results are achieved if the occlusion is proximal, short and recent. The authors discuss selection of patients, technique and results. In the coronary arteries the time factor is crucial. Local intracoronary thrombolysis is used most often as an adjunctive treatment to balloon angioplasty and stent implantation. Good run-off and correction of the flow-limiting lesion greatly improves the outcome in both the peripheral and coronary arteries. PMID- 7998052 TI - [Endothelin--an important factor in coronary heart disease]. AB - The peptide hormone endothelin was initially discovered in endothelial cells. However, it has recently been shown that endothelin is produced by cardiomyocytes too. Endothelin is the most potent of all known vasoconstrictors. The coronary circulation is highly sensitive to endothelin, and intracoronary infusion may lead to lethal coronary spasm. Patients with variant angina pectoris have a higher plasma concentration of endothelin. Moreover, exposure to cold leads to a further increase in endothelin. Therefore increased production of endothelin may be an important mediator of vasospasm. Acute myocardial infarction is followed by an increase in circulating endothelin. Remaining high endothelin levels after myocardial infarction are associated with poor prognosis. Cardiomyocytes increase their production of endothelin during ischemia, and this increase may be harmful, either through an effect on the coronary circulation or by acting directly on the cardiomyocytes. Blockade of endothelin receptors has been shown to reduce the size of an infarction. Thus, intense research is directed towards discovering therapeutical agents that either inhibit production or block the effects of endothelin. Recently, an orally active endothelin receptor antagonist was discovered, and clinically useful therapeutical agents will most probably be available in the near future. PMID- 7998053 TI - [Stress echocardiography with dobutamine. A new method for diagnosis of ischemia]. AB - Dobutamine stress echocardiography was performed in 24 patients with angiographically defined coronary artery stenosis, before they underwent percutaneous transluminal coronary angioplasty. Ischemia was detected on stress ECG in 13 patients. In 19 patients ischemia could be detected with dobutamine stress echocardiography. The method was highly sensitive for detecting ischemia in patients with two vessel or three vessel disease and in patients with affection of only the left anterior descending artery. In patients with one vessel disease the method showed low sensitivity. The most common side effects of dobutamine infusion were flushing and palpitations. One patient suffered atrial fibrillation and one patient had a short and self-limiting ventricular tachycardia. The method seems to be a useful and safe supplementary tool for detecting myocardial ischemia. It is also useful for characterizing the physiological effect of coronary artery stenosis. PMID- 7998054 TI - [Intervention in a high-risk group for cardiovascular disease in Selfjord and Kviteseid. National ambitions transferred to municipal reality]. AB - In 1989 the National Health Screening Service conducted cardiovascular risk factor screening of all men and women aged 40-42 in two small rural municipalities, Seljord and Kviteseid. The local health authorities launched a 3 year follow up programme directed at a group of 38 otherwise healthy persons with elevated risk scores. The programme included individual medical checkups and group sessions to promote smoking cessation, improvements to diet and more physical activity. Only three persons joined any of the groups, while 34 persons attended one medical check-up or more. After three years there were little or no changes in smoking habits or serum cholesterol level in the high risk group. The health benefits of mass screening and individual intervention against cardiovascular risk factors are questioned both from an ethical and a cost benefit perspective. Active case finding and follow-up based on local knowledge of families or persons at high risk may be an alternative in small communities. PMID- 7998055 TI - [Preoperative hand disinfection]. AB - At Telemark Central Hospital we decided to change the procedure for preoperative disinfection of the hands in order to improve antimicrobial efficacy and to minimize skin problems for the personnel. Previously, preoperative disinfection of hands was performed by scrubbing the hand with a detergent containing chlorohexidine (Hibiscrub) which often caused dryness, fissures and dermatitis. In the recent years it has been amply shown that alcoholic solutions have a very good and immediate antibacterial effect on the skin flora, while chlorohexidine has a prolonged effect. In this paper we describe our new procedures for preoperative disinfection of hands and the necessary planning and preparation we undertook to obtain acceptance for these procedures among the personnel. PMID- 7998056 TI - [Results of health care services. A tool for better decision making]. AB - Until recently, post-war health care was characterized first by expansion and later by cost containment. We now appear to have entered a period focusing on assessment and accountability, often described as the outcomes movement. Patients' outcomes are regarded as the most important information on effectiveness and quality. The outcomes movement includes the traditional outcome measures of mortality and morbidity, as well as clinical endpoints, social, mental and physical well-being, general health, quality of life and patient satisfaction. Establishing the effectiveness of medical care in the "real world" is an important aspect of outcomes research. The article discusses the emergence of outcomes research, the central elements of outcomes management, and some critical views on the outcomes initiative. PMID- 7998057 TI - [Cardiovascular survey of 40-year old persons in Hordaland. A critical evaluation]. AB - The results of a heart screening programme in the county of Hordaland showed a high average heart infarction risk score in the two small municipalities, Fedje and Masfjorden where respectively ten and 24 men were screened. A closer look at the results revealed that in Masfjorden the results were affected by two men having very high heart infarction score. Median infarction risk score is a better measure than average infarction risk score, particularly in small municipalities. It does not seem to be a good policy to use the mass media for a preventive and health promotion strategy on the basis of the average infarction risk score. PMID- 7998058 TI - [Medical education at the University of New Mexico and the University of Newcastle]. PMID- 7998059 TI - [Do we have new morbidity data on children?]. PMID- 7998060 TI - [Silicone breast prostheses]. PMID- 7998061 TI - What makes platelets go? The cloning of thrombopoietin. PMID- 7998062 TI - White cell reduction in platelet concentrates and packed red cells by filtration: a multicenter clinical trial. The Trap Study Group. AB - BACKGROUND: Most previous studies on white cell (WBC) reduction by filtration have been small-scale studies conducted under tightly controlled laboratory conditions. Their results would be the ideal, rather than what might be expected during routine operation. STUDY DESIGN AND METHODS: To obtain information on routine filtration of blood components, data have been collected from a large scale, ongoing, multicenter clinical trial designed to determine the effectiveness of WBC reduction in or ultraviolet B radiation of platelet concentrates before transfusion in preventing platelet alloimmunization and platelet transfusion refractoriness. The WBC content of blood components both before and after filtration was determined by automated cell counters and a manual propidium iodide-staining method, respectively. Platelet and red cell losses during filtration were measured. RESULTS: The average platelet losses after filtration were 24 +/- 15 percent and 20 +/- 9 percent for apheresis platelets and pooled platelets, respectively. The frequencies at which filtered platelet concentrates contained high levels of residual WBCs (> 5 x 10(6)) were 7 percent and 5 percent for apheresis platelets and pooled platelets, respectively. Further analysis of the platelet filtration data showed that greater numbers of total initial WBCs in the pooled platelets were associated with increased percentages of filtration failure (> 5 x 10(6) residual WBCs). For packed red cells, the average losses during filtration were 23 +/- 4 percent and 15 +/- 3 percent for CPDA-1 units and Adsol units, respectively. The frequencies at which filtered red cells contained > 5 x 10(6) residual WBCs were 2.7 percent for one type of filter and 0.3 percent for another type of filter. CONCLUSION: There were significant losses of platelets during filtration, which could add to the costs of WBC reduction and lead to possible increases in donor exposures. Filtration failures still occurred, despite careful observation of the standard filtration procedures. The number of total WBCs in pooled platelets before filtration has been identified as an important factor in determining the success of WBC reduction. PMID- 7998063 TI - Characterization of reactions after exclusive transfusion of white cell-reduced cellular blood components. AB - BACKGROUND: Potential adverse effects of white cells (WBCs) within transfused cellular blood components include febrile nonhemolytic transfusion reactions (FNHTRs), alloimmunization, transmission of infectious diseases, transfusion related acute lung injury, and immunomodulation. Although exclusive use of WBC reduced components to prevent alloimmunization and cytomegalovirus transmission has been studied, the use of these components to avert FNHTR has not been examined. STUDY DESIGN AND METHODS: Transfusion reactions (FNHTRs, allergic reactions, and others) were characterized in recipients of 12,277 WBC-reduced single-donor apheresis platelets (SDAPs) and/or red cells (RBCs). Medical and laboratory evaluations for possible infectious and immunologic (alloimmunization) causes of each reaction were undertaken, and the benefit of further modification of components for the prevention of subsequent reactions was also evaluated. RESULTS: Transfusion reactions occurred after 481 (3.92%) of 12,277 transfusions. Allergic reactions occurred more commonly after transfusion of SDAPs (3.69%) than of RBCs (0.51%). Conversely, FNHTRs occurred more commonly after transfusion of RBCs (2.15%) than of SDAPs (1.58%). HLA antibodies were present in a posttransfusion sample from 27 (10.6%) of 255 patients; bacterial contamination was a possible cause of only 2 (0.42%) of 481 reactions. In patients with recurrent FNHTRs, further WBC reduction in components did not wholly prevent further FNHTRs. CONCLUSION: The incidence of FNHTRs and alloimmunization after exclusive transfusion of WBC-reduced RBCs and SDAPs was low. Further WBC reduction in components transfused to patients with a history of recurrent FNHTRs does not completely prevent subsequent reactions. PMID- 7998064 TI - The differentiation of delayed hemolytic and delayed serologic transfusion reactions: incidence and predictors of hemolysis. AB - BACKGROUND: After differentiation of the entities of clinically detectable delayed hemolytic (DHTR) and delayed serologic transfusion reactions (DSTR), previous investigators calculated a DHTR:DSTR incidence ratio of 18:72 from a retrospective review of patients with serologic evidence of DHTR or DSTR. There are no published data on factors that may influence the occurrence of DHTR versus DSTR in a given patient. STUDY DESIGN AND METHODS: Retrospective review was conducted of 292 patients at the Mayo Clinic who, between 1980 and 1992, received a clinical diagnosis of DHTR or DSTR concurrently with a serologic diagnosis. Red cell alloantibody specificity, the activity of the patient's reticuloendothelial system, and concurrent immunosuppression were evaluated as potential predictors of the occurrence of DHTR versus DSTR in different patients. RESULTS: The incidence of DHTR or DSTR was 1 in 1899 allogeneic red cell units transfused, with a DHTR:DSTR ratio of 36:64. Alloantibody specificity was the only variable that affected the occurrence of DHTR versus DSTR at the clinical level, with the anti-Jka and anti-Fya specificities, as well as multiple coexisting specificities, significantly associated with detectable hemolysis (p < 0.05). CONCLUSION: Clinically detectable DHTRs are found to occur more commonly than previously believed when the clinical and serologic diagnoses are made concurrently and appropriate work-ups for hemolysis are ordered. The association of certain alloantibody specificities with detectable DHTRs may have implications for clinical transfusion practice. PMID- 7998066 TI - The bicentennial of transfusion in America. PMID- 7998065 TI - The protein composition of red cell eluates. AB - BACKGROUND: The protein composition of red cell (RBC) eluates has not been extensively studied. The purpose of this study was to determine the IgG content and protein composition of RBC eluates prepared by the acid and xylene elution methods. STUDY DESIGN AND METHODS: Six samples of group O R1R1 RBCs sensitized with anti-D in vitro, six nonsensitized samples of the same group O R1R1 RBCs, and six samples from patients with warm autoimmune hemolytic anemia (WAIHA) were studied. The eluate protein composition was determined by sodium dodecyl sulfate polyacrylamide gel electrophoresis, and immunoglobulin concentrations were estimated by an immunoblot technique using horseradish peroxidase-conjugated anti IgG and 3,3' diaminobenzidine. RESULTS: The protein concentrations of the xylene eluates were significantly greater than those of the acid eluates (37.3 +/- 10.7 and 3.0 +/- 0.4 [SD], respectively; p < 0.005). In all samples, the proportion of IgG was less than 0.13 percent of the total protein content. The acid eluates of sensitized RBCs contained more IgG than the xylene eluates. The antibody titers of eluates from WAIHA RBCs were significantly lower than eluates of in vitro sensitized RBCs (p < 0.005). The estimated molecular weights of the Coomassie blue-stainable protein bands from xylene eluates were 97, 78, 63, 45, 31, 23, and 16 kDa, and those of bands from acid eluates were 97, 78, and 55 kDa. No periodic acid-Schiff reagent-stainable bands were detected. CONCLUSION: These data indicate that IgG represented only a small fraction of the proteins in the eluates and that the protein composition varies with the elution procedure. PMID- 7998067 TI - Large-volume leukapheresis for collection of mononuclear cells for hematopoietic rescue in Hodgkin's disease. AB - BACKGROUND: Peripheral blood mononuclear cells (MNCs) collected by leukapheresis contain hematopoietic stem and progenitor cells that provide autologous hematopoietic rescue after high-dose chemotherapy, an approach that offers a significant benefit to patients with recurrent Hodgkin's disease. However, patients with low MNC counts may require 10 or more standard leukapheresis procedures for the collection of sufficient cells for hematopoietic rescue. STUDY DESIGN AND METHODS: The effectiveness of steady-state large-volume leukapheresis (LVL; 15-35 L blood processed) was evaluated as a method for collecting MNCs for hematopoietic rescue in seven patients with recurrent Hodgkin's disease. LVL was performed on 2 consecutive days per week to collect 7 x 10(8) MNCs per kg. The circulating MNC counts on the first day of LVL and the total numbers of LVL, of MNCs collected, and of liters of blood processed were determined per patient. After high-dose chemotherapy and MNC transfusion, days to granulocyte and platelet engraftment were recorded. RESULTS: On the first day of LVL, patients had median circulating MNCs of 1536 (range, 504-3950) x 10(6) per L. The median number of LVL procedures per patient was four (range, 1.25-6), and the median L per kg of blood processed was 1.57 (range, 0.38-4.03). Simple regression analysis plotting L per kg against initial MNCs gave a curve with the equation y = e(1.42 (6.31 x 10E-4)x) (correlation coefficient = -0.97, R2 = 0.95, exponential fit). Without posttransfusion growth-factor support, median days to granulocyte engraftment were 19 (range, 12-26) and those to platelet transfusion independence were 34.5 (range, 10-57). CONCLUSION: LVL provides a useful method of collecting MNCs for hematopoietic rescue in patients with Hodgkin's disease. The patient's baseline MNC count provides a useful estimate of the volume required for LVL. PMID- 7998068 TI - Pseudothrombocytopenia in plateletpheresis donors. AB - BACKGROUND: EDTA pseudothrombocytopenia (PTCP) is an in vitro artifact in which the anticoagulation of blood with EDTA is associated with in vitro agglutination of platelets, resulting in a spuriously low platelet count. In apheresis donors, whole-blood samples for complete blood counts are routinely drawn into tubes anti coagulated with EDTA. STUDY DESIGN AND METHODS: Records of apheresis donors were examined to identify persons in whom the postdonation counts were less than 100 x 10(9) per L. Identified donors were studied to confirm the presence of PTCP by drawing blood samples into EDTA, heparin, and trisodium citrate for serial platelet counts at room-temperature incubation. Platelet counts in citrated plasma were measured before and after the addition of EDTA. A single HLA-matched component from an identified PTCP donor was monitored for response by corrected count increment in the recipient. RESULTS: A total of nine donations were identified, involving 2 donors from a population of 945 donors (prevalence 0.2%). On testing, both donors were confirmed to have PTCP. The addition of EDTA to citrated plasma did not affect the platelet count. Response in a recipient to an HLA-matched component showed an acceptable corrected count increment. CONCLUSION: PTCP may occur in plateletpheresis donors and result in needless medical referral or donor deferral. PTCP does not appear to alter the yield content of the component or to be passively transferred to a recipient. PMID- 7998069 TI - Donor screening for antibody to hepatitis B core antigen and hepatitis B virus infection in transfusion recipients. AB - BACKGROUND: Testing for antibody to hepatitis B core antigen (anti-HBc) as a surrogate for hepatitis C viremia is no longer needed for blood donor screening. Currently, the important question is how much its use supplements hepatitis B surface antigen (HBsAg) donor screening in preventing transfusion-transmitted hepatitis B virus (HBV) infection. STUDY DESIGN AND METHODS: In a study conducted in the 1970s, 64 blood donors were associated with 15 cases of HBV (1.0%) in 1533 transfusion recipients. Sera from 61 donors at donation and 29 follow-up visits were available for present-day assays for HBsAg, HBV DNA, anti-HBc, and antibody to HBsAg (anti-HBs). RESULTS: HBsAg was found in four previously negative blood donors; HBV DNA was limited to three of these four. Anti-HBc was detected in six HBsAg-negative donors. Two other donors were negative in all assays at donation, but positive for anti-HBc and anti-HBs 2 to 4 months later. The remaining donors were negative for all HBV markers, which left five recipient cases unexplained. No HBV transmission was observed when anti-HBs sample-to-negative control values were > or = 10. CONCLUSION: Some 33 to 50 percent of cases of hepatitis B that could be transmitted by transfusion of blood from HBsAg-negative donors are prevented by anti-HBc screening. Anti-HBc-positive donors unequivocally positive for anti-HBs should be considered noninfectious for HBV and should be allowed to donate. Anti-HBc screening of paid plasmapheresis donors, supplemented by anti HBs testing, would reduce the amount of HBV to be processed by virus inactivation and increase the content of anti-HBs in plasma pools. PMID- 7998070 TI - Evaluation of a new citrate-acetate-NaCl platelet additive solution for the storage of white cell-reduced platelet concentrates obtained from half-strength CPD pooled buffy coats. AB - BACKGROUND: A new citrate-acetate-NaCl platelet additive solution, identified as PAS 2, was developed to prepare platelet concentrates (PCs) from pooled 0.5 CPD buffy coats (BCs). STUDY DESIGN AND METHODS: A study was undertaken to evaluate PAS 2 in vitro (n = 8) and in vivo (n = 9) against a commercially available solution (Plasma-Lyte A). In a paired in vitro study, a comparison was made of platelet and white cell concentration; blood gases and bicarbonate; glucose and lactate concentration; total intracellular concentration of adenine nucleotides and beta-thromboglobulin release. RESULTS: A lower platelet yield (p < 0.0001) and a higher beta-thromboglobulin release (p < 0.01) are observed with Plasma Lyte A. For this reason, half-strength (0.5) CPD was changed to full-strength CPD in the clinical study with Plasma-Lyte A. In a clinical evaluation of nine patients with bone marrow failure, all received PCs with both PAS 2 and Plasma Lyte A that had a shelf life of at least 4 days. Corrected count increments (CCls) were as follows, on average (95% Cl): the CCl at 1 to 4 hours was 22.4 (95% Cl, 15.2-29.4) for PAS 2 and 24.0 (95% Cl, 16.9-31.2) for Plasma-Lyte A; that at 12 to 24 hours was 11.3 (95% Cl, 4.1-18.4) for PAS 2 and 14.2 (95% Cl, 7.1-21.3) for Plasma-Lyte A; and that at 36 to 48 hours was 4.2 (95% Cl, -3.0 11.3) for PAS 2 and 8.7 (95% Cl, 1.1-16.2) for Plasma-Lyte A. No significant difference between the two solutions was found. CONCLUSIONS: PAS 2 and Plasma Lyte A make important contributions to platelet transfusion quality improvement and give an excellent CCl even after 4 days of storage. PMID- 7998072 TI - Hemolytic disease of the newborn due to the Scianna antibody, anti-Sc2. AB - BACKGROUND: Alloantibodies to the low-frequency antigen Scianna 2 (Sc2) are uncommon and not previously reported to cause immune hemolysis. CASE REPORT: A group B, Rh-negative infant born to a group B, Rh-positive mother had a 2+ direct antiglobulin test, as well as modest hyperbilirubinemia and a hematocrit of 45 percent. Ongoing immune hemolysis led to a hematocrit of 17.3 percent on Day 20 of life, and the infant required hospitalization and red cell transfusions. The routine maternal antibody screen was negative, but anti-Sc2 was detected during work-up for a low-frequency red cell antigen, and the father's red cells typed as Sc:1,2. CONCLUSION: Anti-Sc2 can cause clinically significant hemolytic disease of the newborn. Although the antibody is uncommon, its frequency and hemolytic potential may be underappreciated, in part because investigations often are not carried out in the infant whose red cells are ABO-incompatible with maternal blood. PMID- 7998071 TI - NA gene frequencies in the German population, determined by polymerase chain reaction with sequence-specific primers. AB - BACKGROUND: The granulocyte antigens NA1 and NA2 are often targets of granulocyte antibodies causing immune neutropenia. Currently, NA typing relies on the properties of the typing sera or antibodies and the techniques used. Therefore, the technique of polymerase chain reaction with sequence-specific primers (PCR SSP) was adapted for DNA-based NA typing and was used for determining the NA gene frequencies in the German population. STUDY DESIGN AND METHODS: The genomic DNA of 160 unrelated healthy individuals was typed for NA1 and NA2 by PCR-SSP. In 60 granulocyte samples, the NA phenotype was additionally determined by the antigen capture assay and the granulocyte immunofluorescence test (GIFT) and correlated with the genotyping results. RESULTS: Results of the antigen capture assay and PCR-SSP correlated precisely, whereas nine individuals were typed heterozygous only by GIFT. The gene frequencies were 0.35 for NA1 and 0.65 for NA2. CONCLUSION: The NA2 gene is more frequent in the German population than the NA1 gene, as determined by genotyping using PCR-SSP. In contrast to GIFT, which showed an error rate for NA typing of 15 percent, PCR-SSP and the antigen-capture assay are more reliable methods of NA typing of granulocytes. PMID- 7998074 TI - At(a-) phenotype: description of a family and reduced survival of At(a+) red cells in a proposita with anti-Ata. AB - BACKGROUND: There is a paucity of data on the August (At) blood group antigen and clinical significance of anti-Ata. STUDY DESIGN AND METHODS: A proposita with the At(a-) phenotype was identified by the finding of anti-Ata in the cord blood eluate of her fifth live infant. Family members were studied, and a small aliquot of 51Cr-labeled At(a+) red cells was transfused to determine survival. RESULTS: There was no evidence of hemolytic disease of the newborn, as determined by the normal hemoglobin and bilirubin and normal clinical conditions. Six of seven siblings were tested, and two At(a-) female siblings were identified. In contrast to the proposita, neither sister had detectable anti-Ata in her serum, although each has had only one pregnancy. A monocyte monolayer assay performed on serum from the proposita gave a result of 20-percent hemolysis (normal, <3%), which is consistent with a clinically significant antibody. Transfusion of a small volume of allogeneic red cells that were phenotypically matched with the proposita, except for Ata, resulted in a 1-hour survival of 95 percent, but a 24-hour survival of only 18 percent, of the transfused cells. The survival pattern was exponential, which is characteristic of a non-complement-binding IgG antibody. CONCLUSION: Despite the absence of hemolytic disease of the newborn, this example of anti-Ata would appear to be a clinically significant antibody for the purposes of transfusion practice. Therefore, approaches to the management of clinical situations in which transfusion is required or likely should focus on the availability of autologous cells or frozen allogeneic At(a-) red cells. PMID- 7998073 TI - Anomalous ABO inheritance explained by ovum transplantation. AB - BACKGROUND: Modern fertilization techniques can lead to unexpected ABO phenotypes in newborn infants and can raise questions as to maternity, paternity, and infant misidentification. Ovum transplantation can result in an infant with an ABO phenotype that is unexpected, given the birth mother's ABO type. STUDY DESIGN AND METHODS: A group AB, Rh-positive female infant was born to a group O, Rh-positive woman as a result of ovum transplantation. The case report is provided. RESULTS: The birth mother typed group O, Rh-positive both before and after delivery. The infant typed group AB, Rh-positive on cord blood and heelstick specimens. CONCLUSION: Ovum transplantation can result in newborns whose ABO phenotypes are unexpected, in relation to the birth mother's ABO type. To ensure patient privacy, such fertilization techniques may not be clearly documented in the delivery room chart. A complete obstetric history helps prevent repeat phlebotomies, expensive and unnecessary typing studies, and concern of the clinical staff with possible sample or infant misidentification. PMID- 7998075 TI - Erythropoietin in the pathogenesis and treatment of neonatal anemia. PMID- 7998076 TI - James Blundell--pioneer transfusionist. PMID- 7998077 TI - Transfusion triggers. PMID- 7998078 TI - On alanine aminotransferase, hepatitis C virus, and reverse transcription polymerase chain reaction. PMID- 7998079 TI - The importance of installed algorithms. PMID- 7998081 TI - 1st International Conference on New Trends in Clinical and Experimental Immunosuppression. Geneva, Switzerland, February 10-13, 1994. Proceedings. PMID- 7998080 TI - Surrogate testing for AIDS. PMID- 7998082 TI - Increased levels of sTNF receptors following OKT3 treatment. PMID- 7998083 TI - Perioperative albumin and verapamil improve early outcome after cadaver renal transplantation. PMID- 7998084 TI - Effect of single-dose, late treatment with rapamycin on skin allograft survival in ALS- and donor bone marrow cell-treated mice. PMID- 7998085 TI - Azathioprine does not potentiate the immunosuppressive effect of 15 deoxyspergualin in rat heart allografting. PMID- 7998086 TI - Treatment of steroid-resistant acute graft-vs-host disease after allogeneic marrow transplantation with anti-interleukin-2 receptor antibody (BT563). PMID- 7998087 TI - Chronic allograft destruction vs chronic allograft rejection. PMID- 7998088 TI - Severe allograft dysfunction after OKT3-induced human herpes virus-6 reactivation. PMID- 7998089 TI - Cumulative side effects of cyclosporine and Ca antagonists: hypergalactinemia, mastadenoma, and gynecomastia. PMID- 7998090 TI - Complications of using OKT3 for induction of immunosuppression in recipients of kidneys from nonheart beating donors. PMID- 7998091 TI - In vivo immunosuppressive effect of purine nucleoside phosphorylase inhibitor-8 amino-9-benzyl-guanine in canine renal allograft rejection. PMID- 7998092 TI - Prevention of autoimmune destruction of transplanted islets in spontaneously diabetic NOD mice by KH1060, a 20-epi analog of vitamin D: synergy with cyclosporine. PMID- 7998093 TI - Effects of rapamycin on hematopoiesis. PMID- 7998094 TI - Combined high and low dosing of OKT3 for treatment of rejection episodes in renal transplants. PMID- 7998095 TI - Immunosuppression in small bowel transplantation--treatment with a monoclonal IL 2 receptor antibody (NDS 61). PMID- 7998096 TI - RS-61443: a new immunosuppressive agent. PMID- 7998097 TI - Sandimmun neoral, a new oral formulation of cyclosporin A with improved pharmacokinetic characteristics: safety and tolerability in renal transplant patients. PMID- 7998098 TI - Toxicity of IgA anti-CD3 isotype switch variant in vivo. PMID- 7998099 TI - Tolerance induction by soluble CTLA4 in a mouse skin transplant model. PMID- 7998100 TI - Tolerance induction by anti-CD4 MAb treatment in a rat kidney transplantation model. PMID- 7998101 TI - A rat anti-mouse CD3 monoclonal antibody induces long-term skin allograft survival without inducing side effects. PMID- 7998102 TI - Chronic allograft rejection: an update. AB - The aetiology of chronic rejection is most likely multifactorial. The common feature in all organ allografts undergoing chronic rejection is persistent perivascular inflammation and a concentric generalised arteriosclerosis affecting all first and second order intramural arteries. A hypothesis is presented that low-grade damage to the endothelium induces the secretion of growth factors which, in turn, are responsible for smooth muscle cell replication and their influx into intima. PMID- 7998103 TI - ATG in steroid-resistant acute rejection in living related kidney transplantation: long-term evaluation. PMID- 7998104 TI - Different trends in immunosuppression: 10 years' experience with cyclosporine after living related donor renal transplantation. PMID- 7998105 TI - Effects of interleukin-10 on the immunoactivating and immunosuppressive properties of anti-CD3 monoclonal antibody. PMID- 7998106 TI - The potential impact of the reperfusion injury on acute and chronic rejection events following organ transplantation. PMID- 7998107 TI - In vitro effects of artesunate and other antimalarial agents on the function of human lymphocytes and neutrophils. PMID- 7998108 TI - The paradox of ATG monitoring in renal transplantation. PMID- 7998109 TI - Cyclosporine neoral in liver transplant recipients. PMID- 7998110 TI - Therapeutic strategies in autoimmune diseases: the search for tolerance induction. PMID- 7998111 TI - Use of CD3 antibodies in transplantation and autoimmune diseases. PMID- 7998112 TI - Use of cyclosporine in the treatment of autoimmune disorders. PMID- 7998113 TI - Beneficial effects of antithymocyte globulin in severe cases of progressive systemic sclerosis. PMID- 7998114 TI - Review of CTLA4Ig use for allograft immunosuppression. PMID- 7998115 TI - Long-term xenograft survival and suppression of xenoantibody formation in the hamster-to-rat heart transplant model using a combination therapy of leflunomide and cyclosporine. PMID- 7998116 TI - Concentration control: a key to phase I development of immunosuppressive agents. PMID- 7998117 TI - Preferential suppression of lymphocyte proliferation by mycophenolic acid and predicted long-term effects of mycophenolate mofetil in transplantation. PMID- 7998119 TI - Local immunosuppressive therapy in organ transplantation. PMID- 7998118 TI - Immunosuppression of experimental systemic lupus erythematosus and antiphospholipid syndrome. PMID- 7998121 TI - Effect of 15-deoxyspergualin on antibody secretion by specific isotypes producing B-cell hybridomas and myelomas. PMID- 7998120 TI - Comparison of immunosuppressive effects of single-dose and hyperfractionated total body irradiation. PMID- 7998122 TI - Potentiation of cyclosporine A-induced immunosuppression by a lymphocytic low molecular weight peptide. PMID- 7998123 TI - Dislipidemia at different immunosuppressive protocols. PMID- 7998124 TI - Mechanism of action of 15-deoxyspergualin in allograft arteriosclerosis in rat aortic transplants. PMID- 7998125 TI - Effect of mycophenolate mofetil on allograft arteriosclerosis (chronic rejection). PMID- 7998127 TI - Selective elimination of alpha/beta T cells as a model for peripheral T-cell tolerance. PMID- 7998126 TI - Polymerase chain reaction to assess B-cell clonality in clinical conditions at risk for B-cell malignancy. PMID- 7998128 TI - Clinical experience with a monoclonal interleukin-2 receptor antibody (BT 563) for rejection therapy after orthotopic heart transplantation. PMID- 7998129 TI - Effect of anti-CD4 monoclonal antibody and cyclosporine A or a combination of both on chronic rejection in the rat aortic allograft model. PMID- 7998130 TI - Effects of leflunomide and cyclosporine on aortic allograft chronic rejection in the rat. PMID- 7998132 TI - Evidence for an immunosuppressive activity of ganciclovir. PMID- 7998131 TI - Effects of prostaglandin E1 therapy on cyclosporine A and creatinine levels after orthotopic heart transplantation. PMID- 7998133 TI - Endocardial mononuclear cell infiltrates (Quilty effect) in heterotopic cardiac allografts in rapamycin-treated rats. PMID- 7998134 TI - Criteria and assessment of immunosuppressive agents. PMID- 7998135 TI - Molecular pathology of acute and chronic rejection. PMID- 7998137 TI - Myocardial regeneration with satellite cell implantation. PMID- 7998136 TI - Enhancement of cytochrome P450 function of collagen-entrapped hepatocytes by the addition of liver extracellular matrix components. PMID- 7998138 TI - NADPH-diaphorase histochemistry and functional analysis of human fetal striatal brain tissue transplanted into a rodent model of Huntington's disease. PMID- 7998140 TI - The peritoneal cavity: an alternative site for clinical islet transplantation? PMID- 7998139 TI - Local CTLA4Ig synergizes with one-dose anti-LFA-1 to achieve long-term acceptance of pancreatic islet allografts. PMID- 7998141 TI - Outcome of human fetal pancreatic transplants according to implantation site. PMID- 7998142 TI - Development of a method for bulk cryopreservation of purified canine islets. PMID- 7998145 TI - Cryopreservation of adult porcine islets for xenotransplantation. PMID- 7998144 TI - Metabolic evaluation of islets transplanted into the submucosal space. PMID- 7998143 TI - Improved long-term culture of functional human islets in serum-free medium. PMID- 7998146 TI - Liver sinusoidal washout cells transferred to allogeneic recipients reveal tolerogenic properties. AB - Liver sinusoidal washout cells, containing a large fraction of LGL cytotoxic to tumor cell lines in vitro, are less responsive to mitogens and suppress the responsiveness of autologous and third-party PBM to mitogens and autologous mixed lymphocyte culture, compared with autologous portal vein or PBM. They are less immunogenic after IV administration into allogeneic recipients, which can be observed in an in vivo allogeneic lymphocyte cytotoxicity test. Immunization of allogeneic recipients with liver sinusoidal washout cells slightly prolongs heart allograft survival time. PMID- 7998148 TI - Tracheal composites tissue engineered from chondrocytes, tracheal epithelial cells, and synthetic degradable scaffolding. PMID- 7998147 TI - Human hepatocytes differ from rat hepatocytes in their sensitivity to anoxia reoxygenation injury. PMID- 7998149 TI - Nonimmunogenic perinatal islets, transplanted intrathymically to BB/Wor recipients, do not prevent onset of autoimmune diabetes. PMID- 7998150 TI - Conditions for the induction of unresponsiveness to cryopreserved islet allografts with intrathymic islets. PMID- 7998151 TI - Tolerance to peripheral tissue is transient and maintained by tissue-specific class I expression. PMID- 7998152 TI - Transplantation of pancreatic islets in diabetic nonhuman primates. PMID- 7998153 TI - Bone marrow cells transplanted in suspension or in vascularized bone graft repopulate not only bone marrow but also lymphoid organs. PMID- 7998154 TI - Vascularized bone marrow transplantation and graft versus host disease: morphometric analysis of muscle. PMID- 7998155 TI - Class I major histocompatibility complex antigen disparity is not a barrier to successful pancreatic islet cell engraftment. PMID- 7998157 TI - Failure of intrathymic induction of tolerance in outbred rat strains. PMID- 7998156 TI - Treatment with anti-VLA-4 and LFA-1 monoclonal antibodies prolongs intraportal rat islet allograft survival. PMID- 7998158 TI - Blockade of the insulinlike growth factor-I receptor affects intramuscular fetal pancreas/fetal liver isografts in diabetic rats. PMID- 7998159 TI - Interaction between xenografted human fetal pancreas and liver. PMID- 7998161 TI - Functional effects of transplanted human fetal ventral mesencephalic brain tissue from spontaneous abortions into a rodent model of Parkinson's disease. PMID- 7998160 TI - Use of hepatocyte growth factor/scatter factor to increase transplantable human fetal islet cell mass. PMID- 7998162 TI - Transplantation of cholinergic-rich spinal tissue from spontaneously aborted human fetuses into a rodent model of Alzheimer's disease. AB - The results from this study provided the first piece of evidence that intrahippocampal transplants of cholinergic-rich spinal grafts derived from a human fetus can ameliorate the performance of fornix lesioned rats in both spatial reference memory and spatial navigation tasks. Although many questions remain to be answered, these results point to the therapeutic potential of human fetus-derived cholinergic-rich grafts in treating spatial memory impairments. PMID- 7998163 TI - Human fetal liver hematopoietic cell expansion with a novel bioreactor system. PMID- 7998164 TI - Novel transplantation approach: islet cell grafts in cerebral spinal fluid shunts in dogs. PMID- 7998165 TI - Heterotopic hepatocyte transplantation using three-dimensional polymers: evaluation of the stimulatory effects by portacaval shunt or islet cell cotransplantation. PMID- 7998166 TI - Humoral response to encapsulated islets. PMID- 7998167 TI - Nitric oxide in autoimmunity and cell transplantation. PMID- 7998168 TI - Collagen gel matrix promotes islet cell proliferation. PMID- 7998169 TI - Quantitation of isolated pancreatic islets using imaging technology. AB - An automated image analysis routine was developed for the quantitative assessment of isolated pancreatic islets. This approach offers the advantages of standardization, increased precision of EIN determinations, batch analysis without user interaction, and the ability to customize the analysis for specialized requirements. Finally, images may be archived for later review or transmitted electronically for off-site analysis. PMID- 7998170 TI - Laser destruction of human nonislet pancreatic tissue. PMID- 7998171 TI - The geriatric pancreas: an overlooked source of islets for transplantation? PMID- 7998172 TI - Satellite cell transplantation for myocardial repair: labeling techniques. PMID- 7998174 TI - Successful transplantation of chimeric allogeneic-autologous cultured epithelium. PMID- 7998175 TI - Administration of L-GN-monomethyl-arginine in a mouse islet transplant model. PMID- 7998176 TI - S-adenosyl-methionine may protect transplanted hepatocytes against the toxic effects of cytokines. PMID- 7998173 TI - Pretreatment of recipients with mitomycin-C-treated spleen cells induces significant prolongation of cardiac allograft survival in rats. PMID- 7998177 TI - Human-to-baboon bone marrow transplantation after conditioning with nonlethal irradiation. PMID- 7998178 TI - Hepatocytes transplanted intravenously are rapidly destroyed by granulocytes. PMID- 7998179 TI - Myoblast allotransplantation in mice: degree of success varies depending on the efficacy of various immunosuppressive treatments. PMID- 7998180 TI - Prolonged intrathymic parathyroid allograft survival. PMID- 7998181 TI - Combined bone marrow and whole organ transplantation from the same donor. PMID- 7998182 TI - Optimization of liver-directed retroviral gene delivery. PMID- 7998183 TI - Whole body myoblast transfer. PMID- 7998185 TI - Isolation of hepatocytes from a human amyloid liver. PMID- 7998184 TI - Combined intraductal and interstitial distension of human and porcine pancreas with collagenase facilitates digestion of the pancreas and may improve islet yield. PMID- 7998186 TI - Photoconversion to identify DiI-marked cells after hepatocellular transplantation. PMID- 7998187 TI - Generation of neo-tendon using synthetic polymers seeded with tenocytes. PMID- 7998188 TI - Pathogenetic mechanisms underlying reoxygenation injury of perfused rat hepatocytes. PMID- 7998189 TI - Time course of islet release during pancreatic dissociation: an objective method for assessing collagenase activity. PMID- 7998191 TI - Isolation and culture of osteoblast progenitors from human fetal calvarium. PMID- 7998192 TI - Growth of human corneal endothelial cells in vitro. PMID- 7998190 TI - C-peptide secretion from isolated, perifused human islets: effect of culture and cryopreservation. PMID- 7998193 TI - Transplantation of cultured corneal endothelium in rabbits. PMID- 7998194 TI - Human bone marrow obtained from vertebral bodies: cell isolation, phenotyping, progenitor assay, and transplantation. PMID- 7998195 TI - Nutritional status affects the sensitivity to anoxia/reoxygenation in hepatocytes. PMID- 7998196 TI - Large-scale preparation, in vitro function and xenotransplantation of bovine pancreatic islets. PMID- 7998197 TI - Improved yield and survival of porcine islets with newly developed LAP-1 solution. PMID- 7998199 TI - Myoblast injection method regulates cell distribution and fusion. PMID- 7998200 TI - Factors affecting in vitro and in vivo function of isolated porcine islets. PMID- 7998198 TI - Cold ischemic tolerance of human pancreas: assessment of islet recovery and in vitro function. PMID- 7998201 TI - Insulin release in response to glucose from isolated mouse, rat, porcine, bovine, and human pancreatic islets. PMID- 7998203 TI - Cryopreservation of fetal porcine proislets using a fully automated cryounit. PMID- 7998202 TI - Immunologic monitoring after islet allotransplantation in immunosuppressed pigs. PMID- 7998205 TI - Rapid and inexpensive method for the quantitative assessment of donor pancreata for islet isolation. PMID- 7998204 TI - Transplantation of hepatocytes using porous, biodegradable sponges. PMID- 7998207 TI - Comparison of human islet number and viability obtained during purification on Euro-Collins-Ficoll gradients processed on a refrigerated or nonrefrigerated COBE 2991 cell separator. PMID- 7998206 TI - Baboon pancreatic islet isolation and transplantation. PMID- 7998209 TI - Tissue banking of cryopreserved islets for clinical islet transplantation. PMID- 7998208 TI - Application of the hydraulic shaking system method to isolation of human pancreatic islets. PMID- 7998210 TI - Comparison of two microbiological culture techniques used to monitor islet cell isolation contamination. PMID- 7998211 TI - Morphologic analysis of pancreatic islets automated image analysis. PMID- 7998212 TI - Hepatocyte injection in Gunn rats' thymus and spleen. PMID- 7998213 TI - Immune privilege of the testis for islet xenotransplantation (rat to mouse). PMID- 7998214 TI - Fibroblasts diminish the insulin secretory response of HIT-T15 beta cells to glucose. PMID- 7998215 TI - Nitric oxide production increases with intraportal islet xenograft transplantation. PMID- 7998216 TI - Microlymphocytotoxicity assay to assess reactivity of rodent sera to large animal T lymphocytes. PMID- 7998217 TI - The inhibitory role of intraislet somatostatin on glucagon secretion in the isolated perfused human pancreas. PMID- 7998218 TI - Comparison of concordant and discordant xenografted islets of Langerhans rejection. PMID- 7998220 TI - Survival and function of human islets subjected to gamma-radiation. PMID- 7998219 TI - Intrathymic inoculation of donor bone marrow cells prior to xenotransplantation of pig pancreatic islets into diabetic rats. PMID- 7998222 TI - Transfusions of blood cells cause a rise in the bone marrow stem cell population followed by their release to blood circulation. PMID- 7998221 TI - Calcium-mediated induction of anergy in the Jurkat T-cell line. PMID- 7998223 TI - Lymphocyte infiltration following allo- and xenomyoblast transplantation in mice. PMID- 7998224 TI - Donor-specific transfusions prolong heart allograft survival but lymphocytes from the same donor are acutely rejected. PMID- 7998225 TI - Effect of 70% hepatectomy on DNA synthesis in rat hepatocyte isograft into the spleen. PMID- 7998227 TI - MHC-I antigens on cultured human myoblasts. PMID- 7998226 TI - Effect of anti-CD4 and anti-ICAM MAb on survival of fetal pig pancreas grafts in NOD mice. PMID- 7998228 TI - Is there a risk of sensitizing islet recipients to HLA? PMID- 7998229 TI - Preliminary studies of rat pancreas duct epithelial cells in an acute inflammatory wound healing model. PMID- 7998230 TI - Existence of microchimerism in the spleen after intraportal injection in molecular-biological and immunofluorescence study. PMID- 7998231 TI - Intravascular transplantation--allografts in blood stream are destroyed by granulocytes and not lymphocytes. PMID- 7998232 TI - Comparison of two experimental models for combined hepatocyte-islet transplantation. PMID- 7998234 TI - Heat shock and recovery protects pancreatic islets from warm ischemic injury. PMID- 7998233 TI - Allotransplantation of pancreatic islets in rats using multiple donors. PMID- 7998235 TI - Reversal of diabetes by intrapancreatic injection of aminoguanidine liposomes. PMID- 7998236 TI - Ultraviolet ray direct irradiation of pancreatic islets before transplantation. PMID- 7998237 TI - Liver sinusoidal lymphocytes return to liver after intravenous infusion. PMID- 7998238 TI - Propagation of dendritic cell progenitors from mouse liver and their in vivo migration to T-dependent areas of allogeneic lymphoid tissue. PMID- 7998239 TI - In vivo studies of UV-B-irradiated adult pig islets in diabetic mice. PMID- 7998240 TI - Immunomodulation and fish-to-mouse islet xenograft survival. PMID- 7998241 TI - Allotransplantation of cryopreserved human Leydig cells. PMID- 7998242 TI - Prolonged survival of allogeneic Leydig cells after in vitro culture and intramuscular transplantation. PMID- 7998243 TI - Consistent long-term allograft survival in murine pancreatic islet transplants without immunosuppression. PMID- 7998244 TI - Characterization of a novel cell surface molecule discovered on human peripheral blood lymphocytes achieved by a new, rapid technique for identification of molecules with transmembrane regions. PMID- 7998245 TI - Modifications in calcium uptake may contribute to the effects of tumor necrosis factor on fetal islets. PMID- 7998246 TI - Immunohistochemical study of isogeneic fetal liver fragment transplants in rats. PMID- 7998247 TI - Human fetal tissue from spontaneous abortions as potential sources of donor tissue for cell transplantation therapy. PMID- 7998248 TI - Antioxidant enzymatic activities in fetal hepatocytes transplanted into the spleen. PMID- 7998249 TI - Allotransplantation of encapsulated brown adipose cells: magnetic resonance and electron microscopy study. PMID- 7998250 TI - Automated large-scale production of porcine hepatocytes for bioartificial liver support. PMID- 7998251 TI - Cell microencapsulation: a new method. PMID- 7998252 TI - Protamine-heparin membrane for cell microencapsulation. PMID- 7998253 TI - Prolongation of pig islet xenograft survival in polysulfone fiber coil. PMID- 7998254 TI - The effects of duration of diabetes and number of transplanted islets on streptozotocin-diabetic rats. PMID- 7998255 TI - Immunosuppressive effect of stepronin (TS-5010680) in mice. PMID- 7998256 TI - A study of the toxic effects of cyclosporine on testis and adrenal glands in male rats. PMID- 7998257 TI - Adoptively transferred lymphocytes from donors treated with cyclosporine reveal less predilection to migrate to allografts. PMID- 7998258 TI - Successful pregnancy after pancreatic islet autotransplantation. PMID- 7998259 TI - Delayed islet autotransplantation after total pancreatectomy. PMID- 7998260 TI - Simultaneous solid organ, bone marrow, and islet allotransplantation in type I diabetic patients. PMID- 7998261 TI - Efficiency of highly purified islets autotransplanted into the portal vein after total pancreatectomy. PMID- 7998263 TI - Body mass index is an important determinant for human islet isolation outcome. PMID- 7998262 TI - Islets of Langerhans autotransplantation in humans. PMID- 7998264 TI - Iliac artery graft interposition in liver transplantation: our experience in 72 cases. PMID- 7998265 TI - Proceedings of an International Meeting on Liver Transplantation. Milan, Italy, June 2-4, 1994. PMID- 7998266 TI - Right hepatic artery replacement from superior mesenteric artery in combined liver-whole pancreas procurement. Technical problems and liver graft artery reconstruction. PMID- 7998267 TI - Nonanastomotic biliary strictures following right hepatic artery occlusion in transplant recipients. PMID- 7998268 TI - Interventional radiology of the biliary tree after liver transplantation. PMID- 7998269 TI - Incidence of biliary complications following side-to-side choledochocholedochostomy after liver transplantation. PMID- 7998270 TI - Cold ischemia time and biliary complications in liver transplantation. PMID- 7998271 TI - Modified duct-to-duct reconstruction after orthotopic liver transplantation: early and long-term results in 230 procedures. PMID- 7998272 TI - Erosion of the duodenum by a biliary T-tube: an unusual complication of liver transplantation. PMID- 7998273 TI - Piggyback techniques versus classical technique in orthotopic liver transplantation: a review of 75 cases. PMID- 7998274 TI - Milan multicenter experience in liver transplantation for hepatocellular carcinoma. PMID- 7998275 TI - Orthotopic liver transplantation for primary biliary tumors: Milan multicenter experience. PMID- 7998276 TI - Role of total hepatectomy and transplantation in hepatocellular carcinoma. PMID- 7998277 TI - Pretransplant investigations of primary liver tumours with minimal access surgery. PMID- 7998278 TI - Orthotopic liver transplantation for primary sclerosing cholangitis. PMID- 7998279 TI - Liver transplantation for Budd-Chiari syndrome. PMID- 7998280 TI - Pattern of recurrence of hepatocellular carcinoma after liver transplantation: Milan multicenter experience. PMID- 7998281 TI - Clinical features of chronic hepatitis C. PMID- 7998282 TI - Milan multicenter experience in liver transplantation for hepatitis C-related cirrhosis: report of 105 cases. PMID- 7998283 TI - Milan multicenter experience in 96 liver transplants for hepatitis B virus related cirrhosis. PMID- 7998285 TI - Xenotransplantation: problems and approaches. PMID- 7998284 TI - Hepatitis C viral infection and adult liver transplantation: a difficult clinical problem. PMID- 7998286 TI - Early predictive markers of irreversible graft dysfunction after liver transplantation. PMID- 7998287 TI - Central pontine and extrapontine myelinolysis after orthotopic liver transplantation. PMID- 7998289 TI - Liver transplantation for fulminant hepatic failure caused by viral infections. PMID- 7998290 TI - Feasibility of hepatic venous catheterization in patients undergoing orthotopic liver transplantation. PMID- 7998288 TI - Tuberculosis in liver transplant recipients: recurrence after transplantation? PMID- 7998291 TI - Older and fatty liver for hepatic transplantation (OLT) PMID- 7998292 TI - Results of liver transplantation in the North Italy Transplant program. PMID- 7998293 TI - A retrospective evaluation of HLA-A,B, and genomic HLA-DR compatibility in orthotopic liver transplantation. PMID- 7998294 TI - Fatal graft-versus-host-disease: a grave complication after orthotopic liver transplantation. PMID- 7998295 TI - Human hepatocyte growth factor serum levels in early stages after orthotopic liver transplantation. PMID- 7998296 TI - Living related liver transplantation: 36 cases at the University of Hamburg. PMID- 7998297 TI - Monoethylglycinexylidide formation in compensated cirrhosis: correlation with Child-Pugh score. PMID- 7998298 TI - Biliary tract complications in 224 orthotopic liver transplantations. PMID- 7998300 TI - Prostaglandin and lipoperoxide levels and postoperative liver function in human liver transplantation. PMID- 7998299 TI - HLA and ICAM-1 molecule expression and cellular infiltrate analysis in accepted liver allografts. PMID- 7998301 TI - Fatal cardiomyopathy after liver transplantation for genetic hemochromatosis. PMID- 7998302 TI - Orthotopic liver transplantation in 35 patients with fulminant hepatic failure. PMID- 7998303 TI - The role of portal decompression in extremely reduced size canine liver transplantation. PMID- 7998304 TI - Primary hyperoxaluria: a case report of combined liver-kidney transplantation. PMID- 7998305 TI - Pediatric liver transplantation: indications, risk factors, and results. PMID- 7998306 TI - Acute necrotizing pancreatitis due to hepatitis B virus reinfection in a liver transplant recipient. PMID- 7998307 TI - Prostaglandin therapy in primary liver graft nonfunction after orthotopic transplantation. PMID- 7998308 TI - Effect of in situ cold University of Wisconsin (UW) solution flushing and preservation on arterial graft morphology. PMID- 7998309 TI - Successful liver transplantation from a donor with chromosomal abnormality (45,XO). PMID- 7998310 TI - Effect of storage temperature in rat liver transplantation: 4 degrees C is optimal and gives successful 48-hour preservation. PMID- 7998311 TI - Infection-related morbidity and mortality in pediatric C-postnecrotic cirrhotic patients after orthotopic liver transplantation. PMID- 7998312 TI - Endotoxemia following liver transplantation in humans. PMID- 7998313 TI - Postoperative renal function after orthotopic liver transplantation with preservation of the inferior vena cava. PMID- 7998314 TI - Prophylactic treatment of metabolic alterations during revascularization in liver transplantation. PMID- 7998315 TI - Citrate intoxication and blood concentration of ionized calcium in liver transplantation. PMID- 7998316 TI - Right ventricular function during the anhepatic phase in liver transplantation. PMID- 7998317 TI - Renal function during liver transplantation with preservation of the recipient's inferior vena cava. PMID- 7998318 TI - Beta-adrenergic antagonists to prevent bleeding from esophageal varices: a risk during liver transplantation? PMID- 7998319 TI - Single-photon emission computed tomography with 99mTC hexamethylpropyleneamineoxide in cirrhotic patients before and after liver transplantation. PMID- 7998320 TI - Neurologic complications following orthotopic liver transplantation. PMID- 7998321 TI - Outcome of severe pneumonias after orthotopic liver transplantation. PMID- 7998322 TI - The rationing of kidneys for transplantation: US distribution models for cadaveric renal organs. PMID- 7998324 TI - Role of neutrophils during the first 24 hours after liver ischemia and reperfusion injury. PMID- 7998323 TI - Rapidly progressive glomerulonephritis in a renal transplant. PMID- 7998325 TI - OKT3/antithymocyte globulin immunoprophylaxis in the prevention of recurrence of acute vanishing bile duct syndrome in retransplanted patients. PMID- 7998326 TI - Prolonged postprandial hyperglycemia in streptozotocin-induced diabetic mice after intraperitoneal treatment with microencapsulated islets. PMID- 7998327 TI - Pretreatment with increasing doses of donor pancreas or whole blood induces tolerance to allogeneic pancreatic transplantation. PMID- 7998328 TI - Early histopathologic features of tracheal allotransplant rejection: a study in nonimmunosuppressed dogs. PMID- 7998329 TI - Lipid abnormalities in red blood cell and plasma phospholipids in cyclosporine treated heart transplant recipients. PMID- 7998330 TI - Flow cytometry analysis of increased expression of LFA-1/ICAM-1 in TCR-positive lymphocytes infiltrating cardiac allografts in rats. PMID- 7998332 TI - [Emoxipin correction of disorders of lipid peroxidation as affected by a slight excess of oxygen pressure]. AB - The role of the emoxipin (Em.) (2-ethyl-6-methyl-3-oxipyridine) in the correction of the free radical oxidation and allied processes in lung tissues and blood plasma under high-pressure oxygen-prolonged action has been investigated. The studied oxygen exposure (0.3 MPa, 5h) causes the lung stage of oxygen intoxication. It is confirmed by exterior morphological assessment of the lung. The lipid peroxidation increase in lung tissue and blood plasma as well as erythrocyte membranes destabilization result from oxygen exposure. Lipid peroxidation intensity was estimated by determining of content of lipid peroxidation molecular products such as diene conjugates and Shiffs' bases. Erythrocyte membranes stability was evaluated with hemoglobin yield, total iron level and total peroxidase activity in blood plasma. Emoxipin was injected intraperitoneally in a dose 150 mg per 1 kg rats' weight just before the oxygen exposure. Emoxipin is found to improve physiological state of animals and to increase their survival; it normalizes morphology of the lungs and their state; stabilizes erythrocyte membranes injured under oxygen exposure; decreases intensity of lipid peroxidation processes in the lungs and in blood plasma which was previously increased under hyperoxia. PMID- 7998331 TI - [Restoration of the protease--alpha 1-protease inhibitor system after exposure of rats to cold]. AB - The trasilol injection and warming of rats were investigated for their influence on activities of proteinase and alpha-1-proteinase inhibitor (alpha-1PT) after two-hour- and a week-long cold stress. The one-hour return to normal temperature is the most effective method of proteinase-antiproteinase correction after two hour cold stress. Nevertheless, the return of rats to the normal temperature even for 24 hours after a week cold stress is not enough for the proteinase and alpha 1-PI balancing normalization. The trasilol injection is a more effective method in the last case. PMID- 7998333 TI - [Correction of disorders of oxidative processes in toxic liver injury using enterosorption]. AB - Liver injury with tetrachloromethane in white rats is accompanied by accumulation of hydroperoxides in the blood plasma and liver tissue and suppression of antioxidant system (the activity of superoxide dismutase, catalase, glutathione peroxidase, contents of SH-groups and total phospholipids drastically decreases). Ceruloplasmin level in plasma, on the contrary, increases. Enterosorbent SUGS-E in a dose of 19 g/kg partially normalizes violated balance between the activity of free radical processes and state of the antioxidant protection system. PMID- 7998335 TI - [Possibility of participation of proteins binding single-stranded DNA in eukaryotic DNA replication]. AB - Main properties of the single-stranded DNA-binding proteins (SSB-proteins) (type of the protein UP 1 from the calf thymus) have been analyzed. The combination of some properties allows one to say about the strong specificity of the term "SSB proteins type UP 1" and their differences from the HMG-proteins and other DNA binding proteins and enzymes. Basing on the data from literature and the author's data the hypothesis was made that eukaryotic SSB-proteins may be involved in DNA replication, though they have tight relationship with the proteins of heterogeneous nuclear ribonucleoprotein particles. The following fact evidence for the involvement of SSB-proteins in DNA replication: 1) preferential affinity to the single-strand DNA in comparison with the single-strand RNA; 2) the contact between DNA SSB-proteins in chromatin; 3) strong proportional dependence between the content of SSB-proteins in chromatin and the intensity of DNA synthesis; 4) the dependence between the content of SSB-proteins in the cells and genomic size in different organisms; 5) the capacity of SSB-proteins to specific stimulation of DNA replicative synthesis. Apparently SSB-proteins in chromatin modulate the replication with the aid of the unwinding of DNA, stabilizing of the single strand region in this molecule and the activation of the DNA synthesis carried out by DNA polymerase. PMID- 7998334 TI - [Carboxypeptidase N and angiotensin converting enzyme activity in rat blood serum in health and during emotional stress]. AB - The effect of emotional stress on both carboxypeptidase N and angiotensin converting enzyme activities in the blood serum of stable and predisposed rat was studied. It was found that activities of both enzymes in serum of stable rat was higher as compared with those predisposed to emotional stress. During emotional stress a decrease of both enzymes activities was observed. Both enzymes activities in rats with different degrees of tolerance to emotional stress were changed differently. PMID- 7998336 TI - [Enzymes for opioid peptide processing and methods of determining their activity]. AB - Physico-chemical and catalytic properties of opioid peptides metabolism enzymes are considered. Methods for determination of their activity are analyzed. PMID- 7998339 TI - [Aspartate kinase complex of Anabaena variabilis during the early period of development of cyanophage A-1]. AB - Aspartate kinase activity in cells of A. variabilis has been studied in the dynamics of development of virus infection. An early period of reproduction of cyanophage A-1 has been determined to be conjugated with the increase of biosynthesis of amino acids from aspartate family. Five isoenzymes of aspartate kinase were isolated and purified from A. variabilis cells during early development period of cyanophage A-1. Physicochemical properties and influence of amino acids of aspartate family on the activity of homogeneous isoenzymes have been studied. Retroinhibition effect was not observed in infected cyanobacteria cells, which probably enables one to increase 2-7 times the concentration of amino acids in a cell. Such an increase of the amino acids pool is apparently necessary for realization of viral genome strategy. PMID- 7998338 TI - [Interaction of rat hepatic glucose-6-phosphate dehydrogenase with some group specific immobilized ligands]. AB - Conditions of the interaction of rat hepatic glucose-6-phosphate dehydrogenase and some group-specific adsorbents (2'5'-ADP-sepharose Cl-6B, Red sepharose CL-6B and Blue sepharose CL-6B) have been examined. The extent of this interaction was estimated according to such parameters as the volume of enzyme elution (Ve) and the recovery of the enzyme activity (%). The effect of the NADP concentration, values of pH and ionic strength of buffer solution on the parameters of enzyme binding with immobilized ligand was studied. The optimum conditions for the binding and specific elution of the enzyme were elucidated for each of the adsorbent studied. The scheme of glucose-6-phosphate dehydrogenase purification using the adsorbents studied is presented. It allows obtaining the preparation of the enzyme with specific activity about 100-240 U/mg and the extent of purification more than thousand fold. PMID- 7998340 TI - [Identification of membrane proteins of sarcoplasmic reticulum binding 2,4,6 trinitrobenzene sulfonate]. AB - Sarcoplasmic reticulum was treated with 2,4,6-trinitrobenzene sulfonate (TNBS), which binds covalently only with surface amino groups. After solubilization of the membranes and gel-filtration of the SR protein on the Sephadex G-100, the label was discovered in the protein fraction 100-80 and 70-60 kDa. The amino groups of proteins with molecular weight 50-20 kDa are inaccessible for the 2,4,6 TNBS. Incorporation of the latter into proteins increases in presence of KCl. PMID- 7998341 TI - [Interaction of antioxidants with differing chemical structure with a phospholipid bilayer]. AB - Interaction of antioxidant (derivatives of phenol and 1,4-dihydropyridine) with bilayer from lecithin was studied by means of electronic spectroscopy and microcalorimetry. The connection of warm effects and spectral properties was estimated by chemical structure of antioxidants. The effect of physiologically active compounds on the structural and dynamic parameters of the bilayer was determined by means of fluorescent probing. PMID- 7998337 TI - [Phosphorylation of proteins of mRNP-particles of rabbit reticulocytes and their possible role in translation regulation]. AB - Protein kinase activity was found associated with free mRNP particles of rabbit reticulocytes. This enzyme was able to transfer phosphate group(s) from ATP to at least nine proteins of mRNP. Rabbit reticulocytes postmitochondrial supernatant proves the existence of protein phosphatase activity specifically dephosphorylating some mRNP proteins. The role of mRNP proteins phosphorylation- dephosphorylation in translation process is discussed. PMID- 7998342 TI - [Spectral changes in neutral red in a methemoglobin-liposome system]. AB - Peroxidation of lipids induced by methemoglobin in liposomes forms of mixtures of phosphatidylcholine and cardiolipin has been studied. Using the neutral red dye, the pH shift to the base region at the interface has been found. The possible mechanisms of the effect observed are discussed. PMID- 7998343 TI - [Receptor selectivity profile of short enkephalin analogs containing D-ornithine at the second position of the molecule]. AB - The radioreceptor binding assay using a membrane fraction from the rat brain was applied to study binding activity and opiate receptor selectivity of truncated enkephalin analogs (with a free or modified C-terminal carboxyl group) bearing D ornithine at the second position. D-ornithine introduction does not lead to the increase of mu-receptor selectivity as is proposed by the Schwyzer membrane selection model. Some additional modifications (C-terminal amidation or ornithine side chain acetylation) of tetrapeptide molecule were required to reach mu selectivity. Simultaneous replacement of glycine by D-ornithine and C-terminal carboxyl amidation resulted in the potent analog whose selectivity toward the mu receptors was 113 times as high as that of leucine-enkephalin. D-ornithine side chain prolongation by means of the attachment of some amino acid residues (methionine, leucine, proline, asparagine) led to the original branched enkephalin analogs. Studies of their binding activity showed that the best branched analog was only 27 times more selective for mu-vs delta-opiate receptors. PMID- 7998344 TI - [Effect of bis(n-tributyltin)-oxide on the brain GABA-ergic system in vitro]. AB - Wide concentration range (10(-14)-10(-4) M) of bis-(n-tributyltin)-oxide effect on Na(+)-dependent uptake, spontaneous and K(+)-stimulated release, specific receptor binding and GABA metabolism were studied in vitro experiments using brain slices, synaptic membrane fraction and brain tissue homogenates. It is shown that the dependence "concentration-effect" is of non-linear character in all cases. Prevailing suppression of Na(+)-dependent uptake and specific receptor binding during K(+)-stimulated release and metabolism (production and utilization) of GABA activation were marked as a general tendency. Mechanisms of TBTO effect on the studied processes and the involvement of GABA-ergic system in realization of TBTO neurotoxic effects are discussed. PMID- 7998345 TI - [Effect of chemical modification of arginine residues of fibrinogen and its DH fragment on the rate of hydrolysis of these proteins by plasminogen]. AB - Plasminolysis of the fibrinogen arginine and its DH-fragment residues was sufficiently lower in contrast to that of initial proteins. It is supposed that the decrease of the speed of the process is the result of the blocking of centres, adequate to arginyl-binding sites of plasmin molecule. PMID- 7998346 TI - [Role of the non-peptide thymic factor--hypoxanthine system in the proliferation of mature thymocytes of mice and rats]. AB - The incorporation of [8-14C]hypoxanthine radioactive label into the nucleic acids of the mature thymocytes (that do not bind peanut agglutinin) of CBA mice and Wistar rats and the action of non-peptide thymic mitogenic factor (factor) on this process have been studied. It was shown, that the factor, shifting AMP catabolism towards hypoxanthine accumulation, accelerated by 50% the incorporation of hypoxanthine radioactive label into nucleic acids during 3-hour incubation. It is concluded that the factor being an activator of the hypoxanthine accumulation, abrogates the purine limits in thymocytes and activates the "salvage pathway" of purine synthesis which is the primary pathway in thymocytes. The factor is assumed to act as the mitogen on one of the stages of nucleic acids or nucleotides synthesis, but not to act on the guanine hypoxanthine phosphoribosyl transferase. It was shown that the intrathymocyte ratio of hypoxanthine and factor concentrations (hypoxanthine/factor) is higher in rats than in mice. The dependence of proliferative activity on relative levels of both substances was revealed. The stimulation of cell proliferation by the system: factor--hypoxanthine is one of the mechanisms of thymus regeneration at the expense of mature thymocyte population. PMID- 7998347 TI - Analysis of immunogenic properties of nonapeptide TVGRGDPHQ from Bordetella pertussis filamentous hemagglutinin. AB - Immunogenic properties of TVGRGDPHQ nonapeptide which is correspondent to the region 1094-1102 of B. pertussis filamentous hemagglutinin (FHA) were studied. The conjugate of bovine serum albumin with nonapeptide was used for immunization of BALB/c and CBA mice. Antisera of the both lines of mice cross-reacted with a number of antigens, but using affinity chromatography peptide and FHA specific antibodies were extracted. Affinity purified rabbit antibodies to TVGRGPHQ which recognize FHA were also obtained. Therefore the antibodies to the peptide which placed RGD-containing region responsible for macrophage CR3-integrin interaction are capable to distinguish the native antigen. Thus these data are an additional evidence for the nonapeptide use as a component of synthetic vaccine against whooping-cough. PMID- 7998348 TI - [Role of antioxidant enzymes of the fetoplacental complex in neonatal adaptation to maternal diabetes mellitus]. AB - Instability of the system of detoxication of peroxidative products and system of generation of free-radical oxidation of membrane lipids in placenta, funic blood, in amniotic water of mothers with diabetes mellitus and in newborns blood has been found. It is shown, that the exhaustion of antioxidative status of fetoplacental complex connected with the depression of antioxidative activity in blood of the newborns reflects the frustration of adaptation reaction of the newborn's organism, that may increase the risk of perinatal diseases or mortality. PMID- 7998350 TI - [Benzodiazepines--why and to whom?]. PMID- 7998349 TI - [Protective action of 5-hydroxy-6-methyluracil and ferrocenes in nitrite-ion poisoning]. AB - It is shown that ferrocenes and 5-oxy-6-methyluracil efficiently inhibit methemoglobin-formation in experiments in vitro and in vivo. Preliminary administration of ferrocene or 5-oxy-6-methyluracil to laboratory animals essentially increases life time in case of sodium nitrite intoxication. Ferrocene protection from sodium nitrite intoxication normalizes the level of methemoglobin and lipoperoxidation in erythrocytes as well as activity of superoxide dismutase of erythrocytes. Activity of catalase, glutathione reductase and dehydrogenases of the pentosephosphate way were not normalized during ferrocene protection from sodium nitrite intoxication. In case of ferrocene protection the catalase activity during sodium nitrite intoxication remains lowered, while activity of glutathione reductase and dehydrogenases of the pentosephosphate pathway grows sharply. PMID- 7998351 TI - [Varying prescriptions of benzodiazepines in general practice]. AB - The aim of this study was to describe differences in patterns of benzodiazepine prescription in Svendborg. All benzodiazepine prescriptions filled by the two pharmacies in Svendborg between February and 31 March 1990 were registered. During the period, 3364 prescriptions were issued to 2262 persons (1837 tranquillizers and 1272 sedatives). General practitioners provide about 90% of benzodiazepine prescriptions. Practices with a high prescription level accounted for four times as many prescriptions as did practices with a low prescription level. By comparing the prescription level and the composition of the practice population we found that practices with a high prescription level had more women and elderly people enrolled than had the practices with a low prescription level. After standardization for age and sex the difference was reduced from 3.8 to 2.8, but practices with many elderly and female patients still provided more benzodiazepine prescriptions. Major benzodiazepine consumers (> 2 DDD/per day) constricted for 8.8% of the total amount of consumers and accounted for about 25% of the benzodiazepines prescribed during the investigation period. The number of major consumers enrolled in a practice varied between 2.8 to 13.0 per/1,000 patients. The difference in the prescription pattern could to a certain extent be explained by this difference, but there would still be a difference that can not be accounted for in our study. However, we anticipate that this variation could be due to differences in procedures and attitudes to the prescription of benzodiazepines. PMID- 7998352 TI - [Cat-scratch disease and bacillary angiomatosis. An old and a new infectious disease with common etiology?]. AB - A review of cat-scratch disease (CSD) and bacillary angiomatosis (BA) is presented on the basis of published articles. Two newly identified bacteria- Rochalimaea henselae and Afipia felis--have been isolated from patients with CSD. Preliminary investigations seem to indicate that A. felis is an uncommon cause of the disease. CSD may appear as a local suppurative lymphadenopathy or a systemic infection. BA is caused by Rochalimaea species and may appear as cutaneous, mucous or visceral angiomas or bacteremia. It may be a special manifestation of CSD in immunocompromised patients. A description is given of the various pathological pictures and differential diagnosis, and an evaluation is made of the different diagnostic methods, namely visualisation of bacteria in the lesions with Warthin-Starry's silver impregnation, isolation of bacteria, demonstration of bacteria with gene technique and detection of antibodies. The treatment of the disease is discussed. PMID- 7998353 TI - [Menstruation disorders in insulin-dependent diabetes mellitus--epidemiology and causes]. AB - About 20% of all women with insulin-dependent diabetes mellitus (IDDM) have menstrual irregularities. Eight percent have amenorrhea. Fluctuations in blood glucose and insulin concentration are probably contributing factors, but the irregular menstrual cycles are mainly caused by disorders in the central ovulatory mechanisms. Hypothalamic GnRH release is regulated by several neuropeptides. Dopamine and opiates exert an inhibitory effect, and there is evidence for an abnormally high dopaminergic hypothalamic activity among women with IDDM. There might also be disorders of the opioid, serotonergic and GABA'ergic systems, but the consequences of there possibilities remain uncertain. PMID- 7998354 TI - [Resistance of gram-negative bacteria to beta-lactams, aminoglycosides and quinolones]. AB - Antibiotic treatment of infections has traditionally been restrictive, in that use of broad-spectrum antibiotics has been avoided as far as possible. A change in therapeutic principles has occurred in recent years for example with respect to treatment of patients that are immunocompromised, suffering from multiple traumas, recovering from major surgery or have implanted foreign bodies. The use of antibiotics has become more complicated, as one more frequently has to consider the possibility of development of antibiotic resistance in different bacterial species because of long-term treatment regimes in such patients. However, it is important to avoid the spread of broad-spectrum antibiotic regimes such as those for neutropenic patients to less vulnerable patient groups, where narrow-spectrum therapy is usually sufficient. In later years an increased resistance to broad-spectrum antibiotics among enterobacteria has been described abroad. Resistance mechanisms for the most commonly used intravenous antibiotics (beta-lactams, aminoglycosides and quinolones) are described. Resistance mechanisms for the individual antibiotics, cross-resistance and the most important epidemiological aspects are discussed. It is suggested that surveillance of antibiotic use and development of resistance as well as identification of resistance mechanisms be increasingly used so as to continuously ensure optimum treatment regimes. PMID- 7998355 TI - [Tetranectin, a plasma and tissue protein--a prognostic marker of breast and ovarian cancer]. AB - A new plasma protein, tetranectin, was discovered in 1986. It is composed of four non-covalently linked identical peptide chains, each with a molecular weight of 20 kDa. The protein structure is known and it has been found to bind to plasminogen, Ca++ and sulphated polysaccharides. All normal epithelial and mesenchymal cells contain tetranectin in their cytoplasm, but tetranectin is not seen in normal extracellular matrix. The concentration of tetranectin in blood from healthy individuals is about 10 mg/1 with slight sex and age variations. The biological function of the protein is still unknown. The amount of tetranectin in the blood is reduced in patients with various cancer diseases. The degree of tetranectin reduction in the blood from patients with ovarian carcinoma and metastasizing breast carcinoma correlates with survival. While tetranectin is absent in normal extracellular matrix, it is found extracellulary in granulation tissues and in some carcinomas of the breast and the ovary. Lifetables of patients with ovarian carcinoma show that high concentrations of extracellular tetranectin is associated with a poor prognosis. Tetranectin may be a new prognostic marker which should be included in future clinical studies evaluating the prognosis for cancer patients. PMID- 7998356 TI - [Infertility and pregnancy outcome in women with insulin-dependent diabetes. An epidemiological study]. AB - A questionnaire survey comprising an unselected group of 18-49-year old women with insulin-dependent diabetes mellitus and an age comparable control group was performed. Two hundred and forty-five (94%) of the diabetic women and 253 (88%) of the controls answered questions concerning fertility, pregnancy planning and pregnancy outcome. There was no difference in the cumulative rate of pregnancies in the two groups. The prevalence of involuntary infertility among the diabetic women was 17% and similar to that of controls. Compared to controls, diabetic women had significantly fewer pregnancies (mean 1.4 versus 1.7) and fewer births per pregnancy (70% versus 77%), and significantly more diabetic women were nulliparous (48% versus 38%). Only about half of all pregnancies were planned. In general the diabetic women reported that their diabetes had a negative influence on their attitude towards having children. PMID- 7998357 TI - [Resistant gram-negative bacteria at seven intensive care units in Denmark]. AB - A prospective study on the prevalence of resistance to 16 antibiotics in 704 Gram negative bacteria isolated from seven intensive care units was undertaken in 1990. A microtitre panel carrying 16 antibiotics was used for susceptibility testing. The study revealed minor differences in resistance between the participating centres. The overall resistance was relatively low in Denmark, but there was increased resistance among E. coli from intensive care units compared to E. coli isolates from bloodcultures collected in 1988. At one centre the susceptibility of P. aeruginosa to gentamicin was slightly lower than at other centres, indicating a minor outbreak during the collection period. P. aeruginosa and Enterobacteriaceae with inducible production of beta-lactamases showed cross resistance between penicillins and cephalosporins, but not between penicillin/cephalosporins and imipenem gentamicin or ciprofloxacin. The resistance among the repeated isolates of inducible Enterobacteriaceae was slightly higher than among the initial isolates indicating acquisition of resistance or selection of resistant mutants. PMID- 7998358 TI - [Magnetic resonance imaging compared to myelography and CT. Diagnostic value in patients with suspected medullary spinal compression syndrome]. AB - Comparison between myelography (MY) and magnetic resonance imaging (MRI) was carried out in 36 patients with clinical suspicion of spinal cord or root compression due to metastatic disease in the spinal canal. In three patients metastatic lesions were visualized on MY but not on MRI, while there were no cases with a negative MY and a positive MRI. In 44% of the cases MY alone or combined with postmyelographic CT (pm-CT) showed a larger tumour extension than did MRI, while the opposite occurred in 25%. As for detection of bony metastases and tumour masses localized outside the spine there was no difference between MRI and MY + pm-CT. The results indicate that the choice between MRI and MY + pm-CT still can be based on the availability and quality of the procedure at a given institution. PMID- 7998359 TI - [Padma-28, a herbal preparation, increases walking distance in patients with intermittent claudication]. AB - Thirty-six patients with stable intermittent claudication were randomized in a doubleblind study either to treatment with two tablets of Padma-28 twice daily (containing 340 mg dried herbal mixture composed according to an ancient lamaistic prescription) or placebo for four months. Effect of treatment was quantified by measurements of systemic and peripheral systolic blood pressures, and pain-free and maximal walking distances on a tread-mill. The actively treated group attained a significant increase in pain-free walking distance from 115 m (72-218) to 227 m (73- >1000, p < 0.05). The placebo group did not show significant changes in either pain-free or maximal walking distance. Significant changes in systemic or peripheral blood pressures could not be demonstrated in any of the groups. In conclusion, our study has shown that treatment with Padma 28 over a four month period significantly increases the walking distance in patients with stable intermittent claudication of long duration. PMID- 7998360 TI - [High mortality from both natural and unnatural causes. A 10-year follow-up of patients admitted to a center for poisoning treatment after attempted suicide]. AB - While it is well known that suicide rates for suicide attempters are high, mortality rates for all causes needed to be more thoroughly investigated. A Danish 10-year follow-up study of patients who in 1980 were admitted to a poisoning treatment centre after attempted suicide was carried out with the purpose of describing mortality by suicide and other causes of death, and to identify predictive factors. A total of 974 patients aged 15 and over referred to a poisoning treatment centre after deliberate self-poisoning were included in the study. Death by different causes registered in the Danish Death Cause Register was the outcome measure. Over a 10-year follow-up period 306 patients had died; 103 by suicide, 131 from natural causes, 31 by accidents, five were murdered and in 36 cases the cause of death was uncertain. The Standard Mortality Rate (SMR) was 550. The cause-specific SMRs were for suicide 2960, for natural causes 236, for accidents 1256 and for uncertain causes 5459. In Cox-regression analysis high risk factors for later suicide were more than one previous suicide attempt (relative risk (RR) 2.25), living alone (RR 2.28) and age (RR 1.03 per year). Predictors of death by natural causes were pension (RR 1.69), drug abuse (RR 2.72), more than one previous suicide attempt (RR 2.25), age (RR 1.06 per year) and male sex (RR 2.49). The group of patients fulfilling at least one high-risk criteria for later suicide differed significantly from the rest of the patient group regarding frequency of suicide, but both sensitivity and specificity remain low.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7998362 TI - [Hartmann's surgery of colonic diverticulitis. An examination of the colon and the rectum for restoration by ostomy]. PMID- 7998361 TI - [Deaths among drug addicts in Denmark. A forensic medical study of deaths among drug addicts during the period 1991-1992 related to the period 1984-1985]. AB - This study includes all deaths among drug addicts in the years 1991 (n = 219) and 1992 (n = 214) investigated at the three institutes of forensic medicine in Denmark. The results are compared with deaths among drug addicts in 1984-1985. The number of deaths among drug addicts increased by approximately 50% in 1991 1992 compared with 1984-1985. The increase was most significant among drug addicts over 35 years of age. The cause of death was intoxication in three quarters of the cases in 1991-1992. In half of these cases heroin/morphine had caused death, while intoxications caused by methadone accounted for approximately 30% of the cases. In the metropolitan area the frequency of methadone intoxications increased significantly compared with 1984-1985, whereas the number of heroin/morphine intoxications did not change. Outside the metropolitan area, however, a significant increase in heroin/morphine intoxications was noticed. In all parts of the country the number of propoxyphene intoxications decreased to a few annual cases. The most commonly used drugs of abuse were heroin/morphine, diazepam and methadone, often in combination with alcohol. PMID- 7998363 TI - [Pyridoxine dependent seizures]. AB - Pyridoxine dependent seizures is a rare autosomal recessive disorder. Its manifestations are intractable epilepsy leading to death in status epilepticus. Treatment with pyridoxine prevents the seizures and normalizes the EEG. Early diagnosis is important for the intellectual outcome. In Denmark, the disease has occurred in a child of healthy Tamil immigrants, who are first cousins. The child's case story is described and points to awareness of increased occurrence of rare autosomal recessive disorders in immigrants from cultures with traditional consanguinity. We suggest giving a pyridoxine test dosis to all cases of severe epilepsy and status epilepticus in infants younger than 18 months. PMID- 7998364 TI - [Blood group P antigen is the cellular receptor for human parvovirus B 19]. PMID- 7998365 TI - [Costs of treatment in enuresis nocturna]. PMID- 7998366 TI - [Supravaginal or total hysterectomy?]. PMID- 7998368 TI - [A public drug information center in Stockholm]. PMID- 7998369 TI - 3D reconstruction by combining data from sections cut oblique to different unit cell axes. AB - Oblique section reconstruction (OSR) can produce a 3D image from a single micrograph of a section through a 2D or 3D crystal. Resolution, however, is limited in a direction perpendicular to the section plane. When data from sections cut at different orientations are combined, the inherent resolution limitation for single sections can be overcome. In the extreme, combination of sections cut oblique to different principal planes of the unit cell can produce a 3D reconstruction with isotropic resolution. The merging of data from different sections requires determination of section thickness and orientation. A method for section thickness determination is described that is generally applicable event to space groups with little or no symmetry. In addition, an approach has been developed to determine rotational orientation within the hexagonal lattice of insect flight muscle. Finally, an iterative least-squares fitting method is applied to determine a 3D set of deconvoluted structure factors from the merged data. PMID- 7998367 TI - [Trandolapril--a new angiotensin-converting enzyme inhibitor]. PMID- 7998370 TI - Electron diffraction of helical particles. AB - The development of low-dose electron cryo-microscopy has provided the means to see structural details to better than 10 A resolution in helical structures. The application of techniques of image analysis to micrographs can yield accurate phases, but not amplitudes with which to generate three-dimensional maps of the structure. Electron diffraction can provide reliable amplitudes, which can be combined with the phases from the images. In order to collect amplitude data, two problems have to be overcome: the pattern should be obtained from a large well ordered sample of particles, and the inelastic background should be properly subtracted. In this paper, we present three simple methods to produce rafts of helical particles. Using these methods we have obtained electron diffraction patterns from TMV (with data out to 0.28 nm), TMV protein stacked disks (with data out to 0.3 nm) and bacterial flagellar filaments (with data out to 0.5 nm). In addition, we describe the algorithms used to extract the amplitudes from the diffraction patterns. PMID- 7998371 TI - Contrast echocardiography. AB - Myocardial contrast echocardiography (MCE) is an ultrasound imaging technique which promises to provide a safe, noninvasive means of assessing myocardial perfusion. A contrast agent, consisting of a suspension of air-filled microspheres, serves as an ultrasound tracer. When these microspheres are injected intravascularly, the acoustic interface created between the blood and the microspheres enhances the reflected ultrasound signals. Thus, the flow pattern of the microspheres represent the actual blood flow patterns. This paper will review the field of contrast echocardiography, its background and history, the development of ultrasound contrast agents, and a variety of experimental as well as clinical uses. Contrast echocardiography has been utilized in the cardiac catheterization laboratory for the assessment of "risk area," assessment of collateral blood flow and assessment of coronary blood reserve. In the operating room, contrast echo is utilized for the determination of cardioplegic perfusion, assessment of graft patency and evaluation of valvular regurgitation. In the future, with the technical advancement in ultrasound imaging and the active interest and growth in the field of myocardial perfusion imaging using contrast echocardiography, the ability to provide routine real-time perfusion imaging may become a reality. PMID- 7998372 TI - Solid breast neoplasms: differential diagnosis with pulsed Doppler ultrasound. AB - In this prospective study, duplex Doppler ultrasound was used in 95 consecutive patients with solid breast masses to evaluate the presence of neovascular flow. A positive Doppler signal, i.e., a Doppler shift frequency of more than 1 kHz using a 5 MHz insonating frequency, was found in 34 of 57 patients with a carcinoma, and also in three patients with a benign condition. These results indicate that negative findings with pulsed Doppler ultrasound cannot be used to exclude malignancy. However, a frequency shift of more than 1 kHz indicates a high probability for malignancy. In our study a high frequency shift was not related to tumor size. We also evaluated the correlation between a high frequency shift and axillary nodal metastasis. According to our results there is a very low chance of axillary metastasis when no high frequency shifts are found. PMID- 7998374 TI - Preliminary results from attenuation-slope mapping of plaque using intravascular ultrasound. AB - Excised femoral and iliac artery segments have been examined with 20 MHz intravascular ultrasound followed by histological assessment. During the ultrasound examinations, radio-frequency (RF) data were recorded digitally, and used for calculating local values of attenuation slope throughout the tissue, using a frequency-domain technique. The RF data were also reconstructed as conventional ultrasound images, and the attenuation-slope information presented as a threshold colour overlay. Areas identified as degenerative plaque in the histological assessments were usually found to correspond to areas of high attenuation slope, and were clearly identified from the pattern of colours on the combined image. Some examples are presented, illustrating the appearance of various pathologies imaged by this technique. PMID- 7998373 TI - Tissue characterization using intelligent adaptive filter in the diagnosis of diffuse and focal liver disease. AB - In ultrasonic imaging an adaptive two-dimensional filter (ATDF) can suppress randomly generated speckle using the ratio of the local variance to the local mean as the speckle recognition feature (R). The degree of smoothing depends on the difference between the recognition feature in the region to be filtered and the selected reference tissue. We have investigated the clinical application of ATDF for ultrasound B-mode images of liver abnormalities. Using the R values of normal liver as reference values, the ATDF images were displayed. Normal livers (n = 17, R = 2.19 +/- 0.14 M +/- SEM), fatty livers (N = 16, R = 1.89 +/- 0.15) and those with acute hepatitis (N = 10, R = 2.25 +/- 0.18) appeared smooth after application of the adaptive filter, but those diseases with higher R values, such as chronic hepatitis (N = 10, R = 3.04 +/- 0.30), cirrhosis (n = 16, R = 4.44 +/- 0.30), metastases (N = 16, R = 6.43 +/- 0.53) and hepatocellular carcinomas (N = 8, R = 7.92 +/- 0.85), were largely unsmoothed. In conclusion, ATDF allows differentiation of some forms of liver disease and may be helpful in the detection of microfocal echogenic textural lesions. PMID- 7998376 TI - Use of Laplace transform analysis to describe the effect of placental embolisation on umbilical arterial Doppler waveforms in fetal sheep. AB - This is the first study to investigate changes in umbilical arterial Doppler shift waveforms caused by placental embolisation in fetal lambs described by a Laplace transform analysis method. The complete maximum velocity envelope of the waveform was quantified mathematically by the coefficients of the Laplace transform. The changes in the dominant coefficient were significantly correlated with changes in umbilico-placental vascular resistance. The Doppler shift waveforms reproduced those seen clinically in some growth-retarded pregnancies and were acquired in a clinically realistic manner. Increasing vascular resistance two fold in this experiment appeared to produce more consistent changes in the dominant coefficient of the Laplace transform than in the pulsatility index. Both analysis techniques correlated with umbilico-placental vascular resistance and these correlations were not significantly different from each other. PMID- 7998375 TI - A comparison of methods used to calculate ultrasonic myocardial backscatter in the time domain. AB - The cyclic variation of ultrasonic integrated backscatter from the left ventricular posterior wall and interventricular septum of the heart is now well documented in the literature, with minimal values occurring at end-systole and maximal at end-diastole. However, little work has been performed to date to determine whether cyclic cardiac variation of other, more easily derived, backscatter parameters exists. In this study, 20 baseline, epicardial, long-axis cardiac-cycle sequences were obtained from eight open-chest pigs, yielding a total of 285 ultrasonic frames of RF data, which were analysed off-line on a Sun workstation. In addition, the video data from these studies was digitised and collected from each scan. Five backscatter parameters, calculated in the time domain, including (1) the average integrated backscatter; (2) the average of the backscatter power from the log-compressed data; (3) the square of the average of the uncompressed radio frequency (RF) amplitude; (4) the square of the average of the RF amplitude from the log-compressed data; and (5) the square of the average grey-scale video data, were analysed and their variation throughout the cardiac cycle correlated against that obtained from integrated backscatter measurements. The backscatter values obtained were referenced to a gel calibration phantom widely used for 2-D calibration studies. Significant (p < 0.001), good correlation existed between the four backscatter parameters derived from the RF data. Reduced correlation was obtained between the video backscatter parameter and those derived from the RF data. Maximum cyclic variation between systole and diastole was measured from the integrated backscatter parameter and minimum from the three log-compressed data sets. PMID- 7998377 TI - Flow imaging in an end-to-side anastomosis model using two-dimensional velocity vectors. AB - Colour flow Doppler ultrasound images from vessels of complex geometry can be difficult to interpret, thereby limiting the effectiveness of the technique to correctly assess abnormalities and to relate the images to the underlying flow field in a quantitative manner. This paper describes progress in calculating and displaying two-dimensional (2-D) velocity vectors from a 30 degrees end-to-side anastomosis model under steady flow conditions at various Reynolds numbers. Velocity vectors were computed from colour Doppler ultrasound images obtained with a linear array for several incident beam directions, and the results were displayed either as colour-encoded magnitude images or by superimposing the vectors on one of the original colour images. Results are discussed in relation to flow visualization observations and the behaviour of flow in curved vessels. PMID- 7998378 TI - Ultrasound heating in a tissue-bone phantom. AB - Temperature rise generated by focused ultrasound beams was tested on semipermanent tissue-bone phantoms. The phantoms were capped (sealed) plastic hollow cylindrical containers filled with tissue-mimicking material (TMM), in which were imbedded 25 microns diameter copper-constantan thermocouples (TC) and a piece of compact human or cow bone. The acoustic frequency specific attenuation coefficient of TMM was adjusted to be 0.3 dB cm-1 MHz-1 as specified by the FDA for a frequency range of 1-5 MHz. A high density 0.318 cm thick polyethylene sheet was chosen as the material to make caps of the phantoms. A formula developed to estimate the upper limit of temperature rises at tissue-bone interfaces generated by focused ultrasound has been proved to be appropriate experimentally using the semipermanent phantoms. PMID- 7998379 TI - Damage to murine kidney and intestine from exposure to the fields of a piezoelectric lithotripter. AB - Earlier studies, in which murine kidneys were exposed to spherically diverging, spark-generated shock waves, demonstrated extensive hemorrhage in the interior of the organ at peak positive pressures somewhat less than 10 MPa. With comparable pulse numbers, this investigation, using the focal fields of a piezoelectric lithotripter, found no damage to murine kidneys at peak positive pressures as high as 40 MPa. Comparison of these cases and earlier bioeffects studies using pulsed, focused ultrasound leads to the conclusion that damage to murine kidneys is not simply correlated with peak positive pressure or peak negative pressure, nor is spectral content of the wave able to explain the striking differences in damage from these sources. With 200 individual shock waves from the piezoelectric lithotripter applied ventrally, 20-30% of the animals suffered superficial kidney damage (bleeding into the capsule), but the same exposure conditions produced severe intestinal hemorrhage in more than 80% of the animals. PMID- 7998380 TI - Effect of sequential porcine reproductive and respiratory syndrome and swine influenza on the growth and performance of finishing pigs. AB - Sows and gilts on a breeding and finishing unit seroconverted to porcine reproductive and respiratory syndrome (PRRS) virus between February and March 1992. The signs of the disease progressed through the breeding herd to the piglets, weaners, growers and finally the finishing pigs. Forty-eight finishing pigs, on a nutritional experiment in which the individual pigs' food intake was recorded daily, showed signs of PRRS and later of swine influenza virus infection. Blood samples collected at slaughter from 47 of the pigs were seropositive to PRRS virus but seronegative to swine influenza virus. However, an immunocytochemical examination of a representative sample of the lungs of the pigs showed that swine influenza virus was present, despite the negative serological results. The infection of the finishing pigs with PRRS virus was associated with recurrent periods of inappetence and a decline in growth rate and performance. The total financial loss from the sequential infection with the two viruses, in a herd without high health status, was estimated at approximately 7 pounds per pig. PMID- 7998382 TI - Relationship between the persistence of African swine fever and the distribution of Ornithodoros erraticus in the province of Salamanca, Spain. AB - For some time it has been known that the tick Ornithodoros erraticus might be one of the causes of the persistence of African swine fever in the Iberian Peninsula since its introduction in 1960. In the province of Salamanca serological methods have been used to study the relationship between the presence of the tick in different townships and the outbreaks of African swine fever in these townships between 1987 and 1992. The results showed that there was a statistically significant association between the presence of the parasite and the persistence of African swine fever. In townships without O erraticus traditional methods of control are in most cases enough to avoid new outbreaks of the disease, but in areas with O erraticus the traditional methods should be reinforced by other methods for preventing contact between pigs and the parasite. PMID- 7998381 TI - Progress towards the eradication of Aujeszky's disease in New Zealand by vaccination with a subunit vaccine. AB - Attempts to control Aujeszky's disease by vaccination with a glycoprotein-I negative subunit vaccine have been made on nine New Zealand pig farms. Thirty-one to 42 months after the programme of vaccination began, its progress was assessed by measuring the gI-antibody response in pigs from seven of the farms. Three farms had totally eradicated the 'wild' virus infection, one farm was close to achieving complete eradication and the other three farms had made little or no progress. One of the farms which eradicated the 'wild' virus infection achieved this status in two years by combining vaccination with an intensive testing and culling programme; the other two farms had eradicated the 'wild' virus infection by a combination of vaccination and good standards of hygiene without undertaking an intensive culling programme. The farms that had made little or no progress had less satisfactory standards of hygiene and did not practise an intensive testing and culling programme. PMID- 7998383 TI - Use of time-lapse video equipment to determine the efficacy of commercial magnesium blocks in cattle. PMID- 7998384 TI - Effects of ivermectin on pastureland ecology. PMID- 7998385 TI - Animal transport. PMID- 7998386 TI - Animal transport. PMID- 7998387 TI - Rabies policy. PMID- 7998388 TI - Ketosis in newly hatched turkey poults with nervous symptoms. PMID- 7998389 TI - [Simian retroviruses]. PMID- 7998390 TI - [The use of a biotinated probe for the detection of the genomic RNA of the hepatitis A virus in clinical specimens]. AB - A detection technique for hepatitis A virus (HAV) RNA by means of molecular hybridization using ss-biotinated DNA probe on the basis of M13 bacteriophage is described. The technique sensitivity reached 1-10 pg of control DNA or 100-500 pg of HAV. The experiments for detection of HAV carriers among the patients and contacts from foci of HAV outbreaks were carried out. A comparative analysis of the above technique and enzyme immunoassay and amplification technique was done and good coincidence of the results was demonstrated. PMID- 7998391 TI - [Changes in its hemagglutinin during the adaptation of the influenza virus to mice and their role in the acquisition of virulent properties and resistance to serum inhibitors]. AB - Passages of influenza A/USSR/90/77 virus in mouse lungs produced a virulent virus (18th passage) carrying two mutations in hemagglutinin (HA) Asn127-->Asp and Tre89-->Ala. Cloning of this virus revealed two avirulent clones in the population. The analysis of one virulent (clone 7p) and one avirulent (clone 31 np) clones showed them to have both above-mentioned substitutions in HA. Clone 7p replicated in mouse lungs much more effectively than clone 31np, the difference in titres being 2 log10 EID50. In another experiment, the adapted virus (15th passage) did not differ in its antigenic, virulent, and reproductive properties from clone 7p but had only one substitution in HA Asn127-->Asp. Consequently, adaptation to mice required at least one mutation in HA resulting in the loss of glycosylation site. However, acquirement of virulence requires additional factors affecting the level of virus reproduction. Examinations of a number of normal animal sera and erythrocytes showed the mutations in HA accompanying virus adaptation to mice led to the development of resistance to serum inhibitors and changes in the receptor-binding specificity. These properties may be also associated with the loss of glycosylation site in the receptor-binding region of hemagglutinin molecule. PMID- 7998392 TI - [The rapid detection of arboviruses by dot immunoenzyme analysis on membrane filters]. AB - A direct and an indirect variants of dot enzyme immunoassay on membrane filters (dot-EIA) for detection of arbovirus antigens and antibodies were developed. Both variants had similar sensitivity and specificity as compared with the solid-phase enzyme immunoassay usually used for this purpose. The advantages of dot-EIA consist in the possibility of specific detection of antigens in unpurified biological specimens by direct adsorption of the antigen on the membranes, economy aspects, and shortening of the time of analysis. PMID- 7998393 TI - [Genomic changes in strains of the tick-borne encephalitis virus as a result of passages in mice]. AB - Changes in genomes of TBE strains isolated from various sources at early stages of laboratory adaptation to white mice brain were demonstrated by molecular hybridization of nucleic acids with synthetic oligonucleotide probes, complementary RNA sites of reference TBE strains Sofyin and Neudorf. Of the 4 TBE strains passed 6 times through white mice brain in only 1 the level of RNA hybridization with 2 oligonucleotide probes was found changed, whereas in all the 3 tested strains the level of RNA hybridization with 1-2 oligonucleotide probes complementary to strain Sofyin was increased after 7-16 passages in the same system. The most noticeable changes in the genome were detected during readaptation to white mice of a TBE variant selected in passages on H. marginatum marginatum ticks. PMID- 7998394 TI - [The biological properties and variants of the Japanese encephalitis virus from a Russian collection]. AB - Analysis of 10 strains and 7 variants of Japanese encephalitis virus from the collection of the D. I. Ivanovskii Institute of Virology of the Russian Academy of Medical Sciences revealed marked differences between the populations in the complex of biological properties (pathogenicity, reproductive potential, antigenic activity, etc.). Of the Japanese encephalitis virus variants included in the collection attenuated clones 33 and 43 are practically the most interesting as potential candidates for diagnostic and prophylactic preparations. PMID- 7998395 TI - [An experimental infection in lambs by the hepatitis E virus]. AB - Lambs were experimentally infected with a pool of 10% hepatitis E (HE) patient fecal suspension containing HE virus (HEV) isolates Osh-225 and Osh-228 which caused an infection closely resembling experimental HE in primates. Clinical manifestations consisted of acute biochemical and histological hepatitis, virus shedding in feces, the presence of virus-like particles in the peripharyngeal lymph nodes and the contents of small intestine, of HEV RNA in the parenchymal organs of lambs. Susceptibility of lambs to HEV derived from the infected piglets and the possibility of passaging the piglets' HEV in lambs was demonstrated. This passaging led to shortening of the incubation period. PMID- 7998396 TI - [The optimization of the PCR for detecting cytomegalovirus in the urine of newborn infants]. AB - A quantitative comparison of 4-primer PCR-diagnosticum potentials for detection of cytomegalovirus DNA in urine specimens in different methods for DNA isolation was carried out. Comparatively simple DNA isolation procedures were considered for express diagnosis in clinical conditions. A scheme of successive use of diagnostic preparations was proposed. PMID- 7998397 TI - [The interferon reaction of the leukocytes and the natural killer activity in patients with acute viral hepatitis B undergoing interferon treatment]. AB - The interferon response of leukocytes (IRL) alpha and gamma as well as the functional activity of natural killers (NK) were studied in patients with the verified diagnosis of acute viral hepatitis B (AVH-B) treated with leukinferon (a preparation of natural interferon-alpha and cytokines) and reaferon (recombinant alpha 2 interferon). The effect of therapy with LF and RF in patients with AVH-B manifested by an increase in the functional activity of NK up to complete normalization after termination of the course of therapy. In the group of patients treated with LF as a result of therapy IRL-alpha increased by the end of the treatment and in the convalescence period. The observed activation of NK and the IF-alpha system under the effect of IF preparations in patients with AVH-B correlated with enhanced elimination of HBsAg. PMID- 7998398 TI - [The antitumor action of double-stranded interferon inducers (larifan, ridostin) and reaferon in an experiment]. AB - Interferon inducers larifan and rhidostin, and reaferon were shown to exert an inhibiting antitumor effect manifested in the prolongation of the incubation period, decrease of the size of tumors, and longer survival of the animals. The maximal anti-tumor and immunomodulating effect was obtained by combined use of preimmunization with tumor cells and simultaneous administration of reaferon or interferon inducers, larifan and rhidostin. Larifan was also shown to have a greater antitumor activity than rhidostin. Larifan, however, was maximally active only in combination combination with vaccination using syngeneic cells of the virus-induced tumor. In this case levels of alpha and gamma interferons were 2-4 times higher than normally. PMID- 7998399 TI - [The efficacy of an antiviral factor obtained from infected chick embryo fibroblasts in an experimental herpetic infection]. AB - Treatment of mice with an antiviral factor obtained from the culture medium of infected chick embryo fibroblasts protected them against lethal meningoencephalitis caused by herpes simplex virus. The degree of protection varied from 50 to 75% depending on the virus dose, the route of infection, and the mode of the antiviral factor application. PMID- 7998400 TI - [The antiviral properties of 4-iodoantipyrine in an experimental enterovirus infection]. AB - The studies of the therapeutic and prophylactic action of a compound from the group of nonsteroid antiinflammatory substances, iodantipyrine-4, in newborn white mice infected with Coxsackie B3 virus showed the drug to possess both therapeutic and prophylactic activity in the acute period of infection. PMID- 7998401 TI - [The use of monoclonal antibodies for detecting the influenza virus]. AB - The possibilities of using influenza A (Leningrad) 385/80 (H3N2) virus matrix protein-specific FITC-labeled D8 monoclonal antibodies in immunofluorescence assays were investigated. The virus antigen accumulation was detected in chorioallantoic cells of chick embryos. Exhibiting the type-specific properties, the fluorescent antibodies stain the perinuclear space, cytoplasmic membrane, and granular structures in the cytoplasm of infected cells. The haemagglutination test tires in the corresponding specimens were at least 1:16. PMID- 7998402 TI - [The potentials for the comprehensive diagnosis of viral encephalitis in Sverdlovsk Province]. AB - The suggested scheme of laboratory tests helped identify the etiology of viral encephalitides in 65.9% of cases. Diagnosis of tick-borne encephalitis was confirmed by laboratory findings in 93.6% of cases. Patients with Californian encephalitis were detected in the Sverdlovsk region for the first time. A rather high rate of detection of antibodies to Tahyna virus was revealed in the examined population: up to 60%. Influenza origin of encephalitis was recognized in 6.2% of cases, Lyme's disease was diagnosed in 9.3%. PMID- 7998403 TI - Cabinet on nursing administration: caring as an organization way of being. PMID- 7998404 TI - A new road.... PMID- 7998405 TI - Nursing discipline--a forced transition. What happens when a complaint is made against you to the Nursing Care Quality Assurance Commission (formerly Board of Nursing). PMID- 7998406 TI - [Clinical management of hemolytic-uremic syndrome and thrombotic-thrombocytopenic purpura]. AB - BACKGROUND: According to recent research, the hemolytic-uremic syndrome (HUS) and thrombotic-thrombocytopenic purpura (TTP) are variable expressions of the same entity (HUS-TTP) with a common pathomechanism (endothelial cell damage, microthrombi) and common treatment (plasma infusion, plasmapheresis). The condition is still serious with a poor prognosis, and the therapeutic regimen is not yet standardized (cryosupernatant and factor VIII free plasma, steroids, immunoglobulins, anticoagulation, dextrane, prostacyclin, vincristine, splenectomy?). CLINICAL OBSERVATIONS AND REVIEW OF THE LITERATURE: Over an observation period of 15 years we considered the differential diagnosis of HUS TTP in 34 patients, and treated 11 patients with 12 clinical courses specifically with fresh-frozen plasma (plasmapheresis was additionally performed in 10 of them). The 12 courses were retrospectively evaluated and compared with results achieved in the literature. The mean age of the patients was 43 years (+/- 14), and 9 of the 11 patients were women (2 courses given to one woman). The hemolysis improved in 9 of 12 courses, the cerebral manifestation in 3 of 4 cases, and the thrombocytopenia in 2 of 4 cases. Renal failure responded in only 4 of 9 cases and the response was delayed in these patients. Three patients died: one of brain edema due to TTP-specific cerebral microangiopathy and two due to the underlying disease (lupus erythematosus, mixed connective tissue disease). CONCLUSION: Treatment of HUS-TTP is started with fresh-frozen plasma infusions (1-1.5 liters/day), but plasmapheresis should be added 2 days later (3 x 4 liters/week, whereby 2 liters should be given as fresh-frozen plasma). The administration of fresh-frozen plasma must be continued every day. In resistant cases, specific therapy should not be terminated before 4 weeks. PMID- 7998407 TI - [Analysis of the fluoride content of drinking water in Austria 1993]. AB - This study was undertaken to determine the concentration of fluoride ions in drinking water in Austria. The results show that the fluoride ion concentration is sufficient (0.7-1.0 ppm F-) to prevent caries only in very few parts of Lower Austria, Upper Austria, Salzburg, Tirol, Carinthia, and Styria. Hence, additional fluoridation is necessary to achieve successful prophylaxis of caries. PMID- 7998409 TI - [The edentulous areas of the alveolar process in partially edentulous dentition]. PMID- 7998408 TI - Sudden onset of paralysis in a twenty year-old male patient. AB - We report on a twenty year-old male patient who presented with sudden onset of flaccid paralysis. After exclusion of central nervous system involvement, marked hypokalemia pointed to the diagnosis of hypokalemic periodic paralysis, which was completely reversible on oral and parenteral potassium substitution. A provocation test with glucose and insulin administration leading to hypokalemia and incipient paralysis of the limbs confirmed the diagnosis. Pathogenetically, this syndrome is characterized by an excessive shift of potassium ions into the muscle cells. Therapeutic measures include potassium-sparing diuretics, beta blockers, acetazolamide or diclofenamide. In less severe cases, oral potassium may be sufficient to reverse the symptoms. PMID- 7998410 TI - [Lasers in dentistry with special reference to internal temperature in the pulp cavity using the excimer laser with 248 nm of different frequencies]. AB - The purpose of the present study was to examine the heat building up in the pulp cavity during superficial laser preparation, to examine the tooth surface structure at the area treated by laser and to assess the possible duration of treatment on the basis of the rate of tissue removal. Following laser application, a scanning electron microscopic examination of the tooth surface revealed a smooth structure without cracks or fissures. Although the KrF excimer laser (lambda = 248 nm) proved to be applicable in dentistry with regard to its physical properties, several reasons speak against applying it in clinical practice yet. Treatment, for example, would take too much time as sufficiant enamel may only be removed at a high frequency. Moreover, the question of a possible mutagenicity of the excimer laser with a wave-length of 248 nm has not been answered satisfactorily yet. PMID- 7998411 TI - [Retrograde root canal filling]. PMID- 7998412 TI - [Evaluation of the functional and morphologic status of the temporomandibular joint using spiral computerized tomography imaging]. PMID- 7998413 TI - Anti-HBs levels in infants of hepatitis B carrier mothers after delayed active immunization with recombinant vaccine concomitant with DTP-polio vaccine: is there need for a second dose of HBIg? Dutch Study Group on Prevention of Neonatal Hepatitis B. AB - The need for an additional dose of hepatitis B immune globulin (HBIg) was studied by comparing infants receiving 1 ml HBIg at birth followed by hepatitis B immunization, concomitant with DTP-polio vaccine, at 3, 4, 5 and 11 months (schedule E), with infants receiving the same schedule with additional HBIg at 3 months (schedule F). The immune response to recombinant hepatitis B vaccine (20 micrograms) was evaluated in 195 infants born to HBsAg-positive mothers allocated to groups E and F and compared with historic controls who received plasma vaccine (10 micrograms) according to schedule F. Blood samples were drawn at 0, 3, 4, 6, 11, 12 and 24 months of age. No difference in efficacy between the two schedules was observed; 8 and 6% of infants born to HBeAg-positive HBsAg carrier mothers in groups E and F, respectively, became HBsAg carriers. Passively acquired antibodies at birth remained present for about 5 months in most infants. The seroprotection rates (anti-HBs > or = 10 IU l-1) were over 90% at all time points and similar for groups E and F. The titres of anti-HBs attained during the first 6 months were statistically lower (p < or = 0.02) for group E than for group F but similar thereafter. Anti-HBs titres in infants receiving the recombinant vaccine were significantly lower than in infants receiving the plasma vaccine (p << 0.001). Supplemental doses of HBIg in infants receiving a high dose of HBIg ( > 200 IU) at birth and the first dose of vaccine at the age of 3 months are not advised. PMID- 7998414 TI - Non-specific modulation of the immune response with liposomal meningococcal lipopolysaccharide: role of different cells and cytokines. AB - The immunomodulating action of Neisseria meningitidis lipopolysaccharide (LPS) incorporated into liposomes and the activation of different populations of immunocompetent cells or the secretion of cytokines were studied. LPS stimulated an anti-sheep red blood cell (SRBC) plaque-forming cell response in the spleen of mice after simultaneous injection of LPS and SRBC but if LPS was administered 3 days before the immunization with SRBC the response to SRBC was strongly suppressed. After the incorporation of LPS into liposomes the stimulation index was increased from 6 to 19 and the liposomal LPS did not suppress the immune response to SRBC. The incorporation of LPS into liposomes leads to enhancement of B-mitogenic properties of LPS, as liposomal LPS stimulated the proliferation of splenocytes in mice better than free LPS and has no influence on the thymocytes. The liposomal LPS induced more prolonged and significant accumulation of IgM secreting cells in the spleen of mice in comparison with the free LPS. Liposomal LPS also induced more active accumulation of IFN-gamma in human peripheral blood mononuclear cells and less active accumulation of monokines, contributing to the realization of the toxic properties of endotoxin (IL-1 alpha, TNF-alpha, IL-6 and GM-CSF). These results demonstrated that the incorporation of N. meningitidis LPS into liposomes dramatically changed its immunomodulating activity. The data obtained are important for the construction of an adjuvant formulation for synthetic immunogens capable of inducing genetically unrestricted immune responses. PMID- 7998415 TI - Human T-helper cell recognition of an immunodominant epitope of HIV-1 gp120 expressed on the surface of Streptococcus gordonii. AB - Our genetic system for expression of heterologous proteins on the surface of the Gram-positive bacterium Streptococcus gordonii was used to express a human T helper epitope of HIV-1 envelope glycoprotein gp120. In previous work on the naive repertoire of human T-helper cells, it was shown that a 15-amino acid synthetic peptide of the HIV-1 gp120 sequence contained an immunodominant T helper epitope. Synthetic DNA coding for this peptide was cloned in frame within the gene for the streptococcal surface protein M6, and the gene fusion was integrated by transformation into the chromosome of S. gordonii. The expected M6 gp120 fusion protein was found to be expressed on the surface of the recombinant streptococci. To test whether the T epitope could be recognized by T cells when expressed on the bacterial surface within the context of M6, recombinant bacteria were used as antigen in proliferation assays to stimulate the 15-amino acid specific human T-helper clone, in the presence of autologous antigen-presenting cells. Bacteria expressing the T epitope were efficiently recognized by the T cells in culture. In proliferation assays, 10(6)-10(7) bacteria induced responses comparable to those obtained by standard amounts of synthetic peptide (0.02-0.2 micrograms). Recombinant S. gordonii, a candidate for a live vaccine vector, appeared suitable for delivering T epitopes to the immune system. PMID- 7998416 TI - Immunological memory after immunization with oral cholera B subunit--whole-cell vaccine in Swedish volunteers. AB - The capacity of peroral immunization with either two or three doses of B subunit whole cell (B-WC) cholera vaccine to induce immunological memory was examined in Swedish volunteers by testing the immune responses to a single dose of B-WC vaccine given 10 months after the initial immunization. Antibody responses in serum and antibody-secreting cell (ASC) responses in peripheral blood were studied, since these responses seem to reflect the gut mucosal IgA immune responses after oral immunization with B-WC vaccine. Previously immunized volunteers responded to a single dose of B-WC vaccine more frequently and with higher levels of IgA and IgG antitoxin antibodies as well as vibriocidal antibodies in serum than did previously unvaccinated controls. The IgA-ASC responses to cholera toxin B subunit were also higher in primed volunteers than in controls. Two doses of B-WC vaccine were as effective as three doses in inducing immunological memory for cholera immunity. A new B-WC cholera vaccine based on recombinant B subunit had the same capacity as the first generation of B WC vaccine to induce immunological memory for cholera antitoxin immunity. PMID- 7998417 TI - Escherichia coli heat-labile enterotoxin B subunits supplemented with a trace amount of the holotoxin as an adjuvant for nasal influenza vaccine. AB - Escherichia coli heat-labile enterotoxin B subunit (LTB) (2 micrograms), supplemented with a trace amount of the holotoxin (LT) (0.02-20 ng), was examined for the adjuvant effect on antibody (Ab) responses against influenza inactivated haemagglutinin (HA) vaccine in Balb/c mice. Each mouse received a primary intranasal (i.n.) inoculation with the vaccine (1.5 micrograms), prepared from PR8 (H1N1) virus, together with LT-containing LTB and in 4 weeks a second i.n. inoculation of the vaccine alone. The inoculation of the vaccine with the LT containing LTB induced significantly high primary and secondary anti-HA IgA and IgG Ab responses in the nasal wash and the serum, while the vaccine with LTB or less than 2 ng of LT induced little response. The synergistic adjuvant effect was maximal in the concentration of LTB supplemented with 0.2-2 ng of LT. Under these conditions, the augmented IgA and IgG Ab responses, which are cross-protective to PR8 HA molecules, provided complete cross-protection against PR8 virus challenge in mice immunized with heterologous vaccine within the same subtype. These results suggest that LTB containing a trace amount of LT can be used as a potent adjuvant for nasal vaccination of humans against influenza. PMID- 7998419 TI - Vaccine properties of pseudorabies virus strain 783 are not affected by a deletion of 71 base pairs in the promoter/enhancer region of the viral immediate early gene. AB - Strain 783 of pseudorabies virus (PRV) is a genetically engineered vaccine which contains three deletions. The purpose of this study was to examine the effect of one of the deletions, which until now has not been characterized. The deletion occurs within the inverted repeats. Seventy-one base pairs (bp) were deleted, including one of the repeat sequence elements related to the TAATGARATTC boxes detected within the promoter and enhancer region of the immediate early (IE) genes of herpes simplex virus. The deletion affected neither the transcription of the IE gene nor viral growth in vitro. In our animal experiments, one group of pigs was inoculated with the original strain 783 and another with strain 783 which had had the repeat sequences restored. These two groups were then compared to determine the protective efficacy of the two vaccine strains against PRV infection. The deletion in the inverted repeats does not affect the vaccine properties of PRV strain 783: strain 783, with and without the 71 bp deletion in the repeats, protected pigs equally well. PMID- 7998420 TI - Expression of HIV-1 envelope gene by recombinant avipox viruses. AB - Recombinant canarypox (CP) and fowlpox (FP) viruses that contained two forms of the HIV-1 (SF2 strain) env gene were engineered and their expression analysed in chick, simian and human cells. These vectors can efficiently replicate in avian but not in mammalian cells, in which infection is abortive. The two forms, consisting of the entire env open reading frame (IS+) or of the same gene lacking the putative immunosuppressive (IS-) region (amino acids 583-599), were individually inserted into the two virus vector backgrounds. In order to avoid premature transcription termination of the foreign gene and to improve protein expression, a mutagenesis was also performed within the T5NT motif without altering the amino acid sequence. By immunoprecipitation analyses, cells infected with CP and FP recombinants expressed HIV-1 env polypeptides of the appropriate molecular weight. We observed that the gp160 precursor was proteolytically cleaved except in MRC-5 cells infected with the IS- recombinants and that these polypeptides were glycosylated. Further analysis of these recombinant viruses by indirect immunofluorescence and syncytia inhibition assays indicated that the gp120 gp41 complex was present on the surface of infected cells, the number of syncytia being significantly lower when cells were infected by the CPIS- or FPIS- recombinants. Moreover, sera of immunized rabbits revealed the presence of specific antibodies in animals inoculated either with CP or with FP recombinants. These new constructs, which are unable to support a productive infection in human cells, might therefore also be a good anti-HIV-1 candidate vaccine in seropositive hosts. PMID- 7998418 TI - Safety and efficacy of a recombinant yeast-derived pre-S2 + S-containing hepatitis B vaccine (TGP-943): phase 1, 2 and 3 clinical testing. AB - A recombinant yeast-derived pre-S2 + S-containing hepatitis B vaccine (TGP-943) was clinically evaluated through three phases of testing in a total of 2137 volunteers. We observed the immunogenic purity of TGP-943 (phase 1), the inter lot reproducibility of both safety and immunogenicity (phase 2), no significant side-effects, a high capability of inducing both anti-HBs and anti-pre-S2 antibodies (phases 1, 2 and 3), and an ability to induce seroconversion in the majority of vaccines who had been non-responsive to conventional hepatitis B vaccines (phases 2 and 3). In conclusion, TGP-943 is a safe and tolerable vaccine, with special merits: the ability to induce an early anti-pre-S2 response that circumvents the problem of delayed appearance of anti-HBs, and efficacy in non-responders to previous vaccination. PMID- 7998421 TI - Humoral and cell-mediated immunity in rabbits immunized with live non-replicating avipox recombinants expressing the HIV-1SF2 env gene. AB - The canarypox (CP) and fowlpox (FP) viruses, which are unable to replicate productively in non-avian species, have been utilized as live vectors carrying the HIV-1SF2 env gene with the putative immunosuppressive (IS) region complete (CPIS+ and FPIS+) or deleted (CPIS- and FPIS-). To determine if these avipox-env recombinants could be utilized to elicit a specific immune response against HIV 1, six groups of rabbits were immunized with CPIS+, CPIS-, FPIS+, FPIS- constructs or their non-engineered wild-type CPwt or FPwt counterparts. After a primary inoculation and successive boosters, env-specific humoral and cell mediated immunity were demonstrated by ELISA, immunoblots and lymphoproliferation assays. Antibody titres and neutralization activities were higher in CP- than FP inoculated rabbits, the CPIS+ always showing a similar immunogenic capacity to CPIS-. Evidence is also presented indicating that rabbit sera possess group specific antibodies, which were, however, unable to cross-neutralize divergent HIV-1 strains. Although the protective capacity against HIV-1 experimental infection has not yet been determined in these animals, our results suggest that these recombinants might represent promising and safer candidate vaccines against HIV-1. PMID- 7998422 TI - Development of a candidate vaccine against Ross River virus infection. AB - Ross River virus is a mosquito-borne alphavirus which causes several thousand cases of arthritis (epidemic polyarthritis) each year. In this study, binary ethylenimine (BEI) was used to destroy the infectivity of this virus without abolishing the antigenicity or immunogenicity of the virion. Mice immunized intramuscularly with BEI-inactivated virus, with or without Alhydrogel adjuvant, produced antibody which neutralized Ross River virus in vitro, and the mice also failed to develop viraemia when challenged intravenously with live virus. Serum neutralization and in vivo protection were greatest when BEI-inactivated virus was administered without adjuvant. PMID- 7998423 TI - Correlation between in vitro and in vivo behaviour of liposomal antigens. AB - Using conalbumin as a model antigen, we demonstrate in this paper that liposomal antigen differently influences the activation of the immune system depending on the mode of association of the antigen with the liposomal vehicle whether it is by encapsulation or surface linkage. This conclusion is based on in vivo data showing that encapsulated antigen induces a short-lasting response dominated by IgG1 production while surface-linked antigen has a longer-lasting effect characterized by increased production of IgM, IgG2a, IgG3 as well as of IgG1. The in vivo data were complemented by in vitro proliferation studies carried out on spleen cells or macrophage-depleted spleen cells obtained from mice sensitized in vivo and rechallenged in vitro on day 4 following sensitization. Rechallenge was carried out in the absence or presence of anti-IL1. The data indicate that, in contrast to what is generally observed in vivo, liposomes alone potentiate spleen cell proliferative response in a dose-dependent manner. This liposomal effect totally obscures the antigen-specific proliferation that was expected with encapsulated antigen without masking that induced by surface-linked antigen. The mode of antigen association also influences anti-cytokine responsiveness as demonstrated by the insensitivity of the surface-linked antigen response to the presence of anti-IL1 and the significantly decreased response observed with encapsulated antigen under identical conditions. The response to both liposomal antigenic formulations was almost totally abolished in adherent cell-depleted cultures. The overall results therefore suggest that encapsulated and surface linked antigens activated different immune pathways. PMID- 7998424 TI - Induction of humoral and cellular immunity to simian immunodeficiency virus: what are the requirements for protection? AB - In an effort to produce a strong humoral and cellular immune response that might protect against simian immunodeficiency virus (SIV) infection, groups of five rhesus macaques each were immunized intramuscularly at 0, 2 and 6 months with 100 micrograms of an inactivated preparation of SIV/Delta B670 in either an oil-in water emulsion with Ribi Detox, containing mycobacterial cell wall skeleton and monophosphoryl lipid A (CWS/MPL) (group A) or a water-in-oil emulsion with incomplete Freund's adjuvant, containing CWS/MPL for the first two injections (group B). Animals were challenged with 10-100 monkey ID50 of monkey-cell-grown SIVmac251 3 months after the last injection, along with a group of four unvaccinated controls. Group B animals demonstrated the strongest immune responses following immunization, including neutralizing antibody titres against the challenge virus ranging from 160 to 320 and SIV-specific ELISA titres ranging from 10(5)-10(6) on the day of challenge, as well as strong in vitro lymphoproliferative and interleukin-2 (IL-2) production responses to the immunogen. Neutralizing antibody was not detectable in group A animals, ELISA titres were lower (10(2)-10(4)), no in vitro lymphoproliferative responses were observed, and in vitro IL-2 production was less pronounced. No protection against challenge was observed in either group. Moreover, group B animals exhibited a more pronounced clinical response following challenge than either group A animals or controls, consisting of hyperthermia and a greater degree of lymphadenopathy on day 7, followed by hypothermia and generally higher levels of serum viraemia on day 14.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7998425 TI - HIV-1 envelope-elicited neutralizing antibody titres correlate with protection and virus load in chimpanzees. AB - In an attempt to compare the protective effect of vaccination with two forms of envelope antigens, and to define immunological correlates of protection against HIV infection, chimpanzees were vaccinated with either recombinant gp160 or gp120. Homologous HIV challenge was performed 3 weeks after the fourth immunization. The animal with the highest level of serum neutralizing antibodies (gp160 immunogen) was protected against HIV infection. All other chimpanzees became infected, but displayed various levels of infected PBMCs. The postchallenge data gave rise to the following conclusions: (1) protection correlated with the level of the serological immune response, but not with the nature of immunogen (gp120 versus gp160); (2) the virus-neutralizing titre at day of challenge correlated with protection from infection; (3) the relative magnitude of the lymphoproliferative T-cell response at day of challenge did not correlate with any protective effect; (4) the peak numbers of virus-infected PBMCs in vaccinated animals were lower than those observed in control animals, and this effect was correlated with the intensity of the antibody response at day of challenge. This raises the possibility that a beneficial effect of HIV vaccination may be achieved in a situation where sterile immunity is not consistently obtained. PMID- 7998427 TI - Method of administration of rabies immune globulin. PMID- 7998426 TI - Acute hepatitis B in households of chronic carriers. PMID- 7998428 TI - [We learned to handle drug problems in school]. PMID- 7998429 TI - [Knowledge of nursing care runs the risk of vanishing]. PMID- 7998431 TI - [Cost of care will be determined with a clock in front of you]. PMID- 7998430 TI - [There is a glow in stroke care]. PMID- 7998432 TI - [We have to fight for justice in the labor market]. PMID- 7998433 TI - [Open laboratory gives patients quick answers]. PMID- 7998435 TI - [Where does the discussion on prioritizing in health care take us?]. PMID- 7998434 TI - [When the Dean leaves the problems will be solved]. PMID- 7998438 TI - [Rapid development of teleradiology in Sweden]. PMID- 7998436 TI - [Principles and example in prioritization administration]. PMID- 7998437 TI - [Together in a homelike environment during the last stage of life]. PMID- 7998439 TI - [Patients on video--a question of ethics]. PMID- 7998440 TI - [Telephone counseling should be better documented]. PMID- 7998441 TI - [Different demand and direction provides nursing college profile]. PMID- 7998443 TI - [A rolling consultation spreads public health in sparsely populated areas. Interview by Jan Thomasson]. PMID- 7998444 TI - [Idealistic work and Swedish aide keeps San Alberto clinics alive]. PMID- 7998445 TI - [Jane leads collaboration with health care pioneers in the East. Interview by Elisabet Forslind]. PMID- 7998442 TI - [Equal education is goal for SHSTF policy]. PMID- 7998446 TI - [Wages should follow job developments]. PMID- 7998447 TI - [Describe entire contents in the open health care form]. PMID- 7998448 TI - [Helena takes on drug addicts on her own terms]. PMID- 7998449 TI - [Roentgen pictures via telenet saves both time and money]. PMID- 7998451 TI - [Health planning. Goal is to prevent illness]. PMID- 7998450 TI - [Women's reproductive health. Midwives' preventive activities lowers abortion rate]. PMID- 7998453 TI - [Class distinction in health. Relationship between life expectancy and income is strong]. PMID- 7998452 TI - [Allergy prevention activities. "Where the vision is of an allergy-free nation"]. PMID- 7998455 TI - [Insomnia: talk with patients on what lies behind it]. PMID- 7998454 TI - [Insomnia: sleep disturbance is a public health problem]. PMID- 7998456 TI - [Health promotion in school. "You can"--teach children to live healthy]. PMID- 7998457 TI - [Accident prevention. Fewer children with head injuries following helmet campaign]. PMID- 7998458 TI - [Uppsala model for smoking cessation. Smokers formulate own motivation for smoking cessation]. PMID- 7998459 TI - [Lower radon levels for the children's sake!]. PMID- 7998460 TI - [On the way towards pensions]. PMID- 7998462 TI - [Frightened into silence]. PMID- 7998463 TI - [A set-back for women]. PMID- 7998461 TI - [Liability case. Contrast medium harms infants. Physicians and nurses receive warning]. PMID- 7998464 TI - [Public health. Here is the foundation of an ailing class society]. PMID- 7998465 TI - [Harassed nurse got satisfaction in the end]. PMID- 7998466 TI - [Denmark needs Swedish nurses]. PMID- 7998467 TI - [Readers speak out. See research as a challenge]. PMID- 7998468 TI - [Isaac gets a new life for developmentally disabled]. PMID- 7998469 TI - [Sweden's freshest county ventures into public health]. PMID- 7998470 TI - [Progress in knowledge about fibrinolysis regulation]. AB - Plasminogen activator inhibitor-1 (PAI-1) plays particularly important role in regulation of homeostasis of fibrinolytic system. It neutralizes active molecules of tissue-type and urokinase-type plasminogen activators. PAI-1 is synthesized mainly in endothelial cells but it is present also in other cells. It was found in vitro that elevated expression of PAI-1 gene and increase in PAI-1 concentration released from endothelium is caused by many different biologically active substances. Among them there are thrombin, lipopolysaccharides, cell growth factors, cytokines and also glucocorticoids and phorbol esters. In this work mechanisms of regulation of PAI-1 synthesis and role of this protein in homeostasis of fibrinolytic system are described. PMID- 7998471 TI - [Markers of intravascular activation of coagulation]. AB - New markers of intravascular activation of coagulation have been developed, based on advance in our understanding of the biochemistry of the haemostatic mechanism. These are sensitive methods for measuring of peptides liberated with the generation of thrombin (factor IX activation peptide, factor X activation peptide, peptide F1 + 2), for measuring concentration of enzyme-inhibitor complexes (eg. thrombin-antithrombin III-TAT complexes), as well as for investigating the effect of thrombin on fibrinogen (fibrinopeptide A-FPA) or on protein C (protein C activation peptide). Studies employing these markers indicate that a state of hypercoagulability can be detected in the blood of humans prior to the appearance of thrombotic phenomena. However, further studies will be required to determine whether these methods can identify individuals who are entering a clinically relevant hypercoagulable state as well as to monitor an antithrombotic treatment. PMID- 7998472 TI - [Laboratory methods of estimating blood platelet activation]. AB - Important discoveries of the last twenty years indicate that blood platelets play an important role in the etiopathogenesis of many serious diseases. These include atherosclerosis with its acute vascular complications like myocardial infarction and many forms of disseminated intravascular coagulation. Their role is not limited here to platelet participation in thrombus formation. This is why we are constantly searching for a method which will allow to detect platelet activation in vivo before any important damage to vital organs and tissues will take place. Despite the implementation of sophisticated modern laboratory techniques reliable assessment of such activation poses still a clinical and laboratory problem. PMID- 7998473 TI - [Inherited thrombophilia]. AB - The prevalence of inherited thrombophilia in the general population (1 in 2,500) is higher than that of hemophilia and related bleeding disorders. Well established causes of thrombophilia include deficiencies of natural coagulation inhibitors: antithrombin III, protein C and protein S. It is likely that other inherited disorders, such as deficiency of the second cofactor for activated protein C, deficiency of heparin cofactor II, hypo- and dysplasminogenemias, dysfibrinogenemias and homocysteinemia, may predispose to thrombosis. This review discusses clinical and laboratory aspects of these disorders and summarizes the management of individuals with inherited thrombophilia. PMID- 7998474 TI - [Progress in understanding mechanisms of blood coagulation activation]. PMID- 7998475 TI - [Role of fibrinogen in cardiovascular diseases]. AB - In cardiovascular diseases increased fibrinogen concentration is usually observed. Fibrinogen is involved in platelet aggregation, affects blood coagulation and has direct on the vascular wall. Epidemiological studies identify fibrinogen as a major independent risk factor for ischemic heart disease. PMID- 7998476 TI - [Serotonin--blood platelets, vessels]. AB - The synthesis and metabolism of serotonin (5-HT), and different populations of 5 HT receptor is described in this paper. Since the platelets are the main source of serotonin in the blood, the interactions of this amine with platelets and vessels wall one also discussed. In this context, the author indicate the role of serotonin in the pathophysiology of cardiovascular system. PMID- 7998477 TI - [Diagnostic antiphospholipid antibodies and their clinical significance]. AB - Lupus anticoagulant and anticardiolipin antibodies belong to a heterogeneous family of antiphospholipid antibodies, directed probably against complexes composed of protein and negatively charged phospholipids. The antiphospholipid syndrome consists in the association of antiphospholipid antibodies and both venous and arterial occlusive events. The mechanism by which the antiphospholipid antibodies could induce thrombosis remains unclear. PMID- 7998478 TI - Prostacyclin and nitric oxide. PMID- 7998480 TI - Perturbation of thyroid hormone homeostasis in the adult and brain function. AB - Although a critical role of thyroid hormones in mammalian brain development is well established and extensively documented, the adult CNS is often thought to be a thyroid hormone-insensitive organ. The presence in the adult brain of thyroid hormone, along with high levels of nuclear T3 receptors and the strict regulation of intracerebral T3 levels, coupled with overt psychomotor and cognitive dysfunctions in adult-onset dysthyroidism, casts doubt upon this assumption. We have therefore investigated the influence of thyroid hormones on the biochemistry, metabolism and molecular biology of adult rat brain regions and confluent neurons and astrocytes in culture. Our results and those in the literature show that brain nuclear T3 receptor and angiotensinogen mRNA levels and 5'D-II activity are dependent upon normal thyroid hormone concentrations. Several subfractions of cell signalling proteins (G protein alpha subunits) are compromised in hypo- and hyperthyroidism and the activities of protein kinases A and C are up-regulated in the hypothyroid state in a brain region-specific manner. The activities of acid phosphatase and aryl sulphatase A are compromised in the brain of hypothyroid rats, indicating a degree of lysosomal dysfunction, and several neurotransmitter metabolic enzymes and receptor systems are also affected. Metabolic experiments indicate that glutamate and acetate metabolism are compromised in the hypothyroid state, although glucose metabolism remains normal. Primary cultures of confluent neurons and astrocytes also strongly indicate a critical role for thyroid hormones in the control of amino acid uptake, protein synthesis, glycoprotein synthesis and 2-deoxyglucose uptake, in a cell-specific manner.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7998479 TI - Transport of thyroid hormones to target tissues. AB - Endemic iodine deficiency is associated with maternal hypothyroxinemia and a relatively high incidence of neurological disorders in the offspring. The previous assumption that the placenta is impermeable to maternal thyroid hormone, has resulted in the erroneous suggestion that iodine per se has an essential role in brain development. Furthermore, the observed factorial rise in thyroxine binding globulin (TBG) in pregnancy has often been misinterpreted as preventing thyroid hormone loss to either the fetal compartment or excretory systems. However, physiochemical analysis of the role of specific binding proteins in hormone delivery, combined with epidemiological evidence and evolutionary considerations has led us to postulate that a) maternal thyroxine (T4) is transported to the fetus, and is of crucial importance in early fetal development, and b) TBG forms part of a control system specifically designed to maintain at an optimal level the T4 environment to which the developing fetus is exposed. Placental transfer of maternal T4 in a variety of mammalian species (including humans) is now well established. Further experimental studies in rats have shown that perturbation of the intrauterine thyroid hormone environment during critical phases of brain development results in a spectrum of biochemical dysgenesis. For example, in fetal brains deriving from hypothyroxinemic (Tx) rat dams, severe disruption of phosphate metabolism is observed and the ontogenesis of two enzyme activities associated with growth control, protein kinase C and ornithine decarboxylase, are compromised. Development of brain function is also impaired, as evidenced by the dysgenesis of certain neurotransmitter metabolic activities (choline acetyltransferase and DOPA decarboxylase).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7998481 TI - Thyroxine treatment of benign goiter. AB - The conservative therapy of endemic as well as sporadic goiter is the TSH suppressive therapy with thyroxine. In the last decade, this therapeutic concept as well as the role of TSH in goiter development fell into disrepute. It has become evident that TSH mainly regulates thyroid function, induces hypertrophy of the follicular cells and increases the blood flow within the thyroid gland. The intrathyroidal iodine deficiency itself and the increased activity of local growth factors, however, may be the main causes of initiation, promotion and maintenance of hyperplasia. The clinical observation of a "shrinking" goiter during thyroxine therapy is now well established by ultrasound investigations as a decrease in goiter volume of maximal 30 to 40% within the first few months of treatment. Afterwards no further significant reduction in goiter size has been demonstrated so far. Stopping treatment results in an increase of goiter volume within a few weeks. These rapid changes can only be related to changes in the size of cells, follicles and vessels and not to growth or necrosis of thyroid cells. In comparison, treatment of endemic goiter with iodine also lead to a reduction of hypertrophy, but as demonstrated in rats, also to a reduction of hyperplasia. Treatment with iodine compared to thyroxine has a prolonged effect on reduction of goiter size even after withdrawal of the substitution. The main question that has to be discussed is whether the hyperplastic part of an endemic goiter in adults can be treated at all, either with thyroxine or iodine or both.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7998482 TI - The therapeutic use of triiodothyronine and high dose thyroxine in psychiatric disorder. AB - An intimate association between disturbances of thyroid hormone homeostasis and behavior has been recognized for a long time already: Hyper- and hypothyroidism can induce disturbances of mood and intellectual function (in severe cases even psychosis can be mimicked). Reciprocally many psychiatric disturbances, such as major depression and manic depressive disease have associated with them disturbances of peripheral thyroid hormone metabolism. Approximately 10% of depressed persons seem to have subclinical hypothyroidism and another approximately 35% have a blunted TSH response to TRH. The use of lithium clearly increases these numbers. In some cases a positive correlation between elevated T4 and the speed of response to antidepressant drugs has been reported. Patients with manic depressive disease respond less well to treatment with lithium when they have a so called "rapid cycling disorder" (defined as more than 4 episodes of disturbed behavior a year). These patients were shown to have a comparably high incidence (up to 50%) of mild subclinical hypothyroidism. In an open study of 11 patients (10 females--9 of them premenopausal--1 male) with rapid cycling disorder adjunctive treatment with TSH suppressive doses of T4 (T4 levels at approximately 150% of normal) reduced the manic and depressive phases in both amplitude and frequency and even led to remittance in some patients. T4 treatment was begun only after stable "therapeutic" blood levels of lithium carbonate and/or anticonvulsants have been reached, since it has been shown that T4 therapy alone can precipitate dysphoric manic like symptoms which require treatment with neuroleptics. Careful evaluation of possible side effects like osteoporosis revealed surprisingly an even higher bone density in treated patients.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7998483 TI - Resistance to thyroid hormone--an uncommon cause of thyroxine excess and inappropriate TSH secretion. AB - Resistance to thyroid hormone (RTH) is an uncommon inherited cause of hyperthyroxinemia with inappropriate TSH secretion. The syndromes are characterized by reduced target tissue responsiveness to circulating free thyroid hormones. The differential diagnosis to other diseases with similar laboratory results (high T4 with normal TSH) like familial dysalbuminemia or antibodies against iodothyronines or TSH is now possible with the appropriate use of new assays for free thyroid hormones. In the presence of thyrotoxic symptoms it may be difficult to differentiate the syndrome from a TSH-secreting pituitary tumour. Familial occurrence and a normal TSH-response to TRH that can not be suppressed by T3 are characteristic features of RTH, that may be helpful in that respect. The majority of RTH cases are dominantly inherited and have highly variable clinical signs and symptoms. There are, however, mainly two forms of the syndrome that have been shown to overlap clinically and biochemically, namely a generalised resistance (GRTH) and a more "selective" pituitary resistance to thyroid hormones (PRTH). The absence of thyrotoxic symptoms rather suggests GRTH, whereas thyrotoxic signs seem to be characteristic for PRTH. Following the cloning of thyroid hormone receptors, familial GRTH was shown to be tightly linked to the TR-(Thyroid hormone receptor)-beta gene locus. Molecular genetic studies have shown that even within a single kindred the same receptor mutation was associated with both, GRTH or PRTH, and therefore suggest that these two forms represent part of a variable clinical spectrum of a single genetic disorder.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7998485 TI - Proceedings and dissertation abstracts. PMID- 7998484 TI - Effects of thyroxine excess on peripheral organs. AB - Aim of this paper is to review the effects of T4 excess due to exogenous thyroid hormone administration on target organs, with particular regard to heart, bone, liver and pituitary. Therapy with TSH-suppressive doses of T4 has been shown in a cross sectional echocardiographic study to increase left ventricular contractility and to induce mild myocardial hypertrophy. Whether the latter represents a risk for the patients remains a matter of debate. Clinically it does not seem to be important. The long-term evaluation of T4-therapy has provided controversial results. Some have reported that T4-treated patients under the age of 65 have an increased risk of ischemic heart disease, whereas others were unable to find any change in morbidity, mortality and quality of life, including cardiovascular events. Thyroid hormones enhance both osteoblastic and osteoclastic activities in cortical and trabecular bone. Overt hyperthyroidism is well known to represent a risk factor for osteoporosis. Studies in the late eighties have suggested a reduced bone density in T4-treated patients, with a particular risk for cortical bone in postmenopausal women. More recent studies have failed to show any substantial T4-related change in bone mass. Taken together the evidence of the literature suggests that TSH-suppressive therapy with T4 is, if well controlled, probably not associated with significant loss of bone mass at least in premenopausal women. A mild elevation of the activity of hepatic enzymes (glutathione-S-transferase, gamma glutamyltransferase, alanine amino-transferase, angiotensin-converting enzyme) has been observed in patients under T4 treatment in TSH-suppressive doses.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7998486 TI - Clinical significance of the finding of subarachnoid blood on CT scan after head injury. AB - The population analysed consisted of 268 out of 819 patients of a European nimodipine multicentre trial on severe head injury, whose first CT scan after injury showed signs of subarachnoid bleeding. The study demonstrated the importance of traumatic subarachnoid haemorrhage (tSAH) per se as a prognostic factor. The outcome of patients with tSAH is significantly worse than that of patients whose first CT does not show subarachnoid blood (noSAH). The outcome was unfavourable (dead, persistent vegetative state, severe disability) in 60% of tSAH patients compared to 30% of noSAH patients (p < 0.001). The difference in mortality was 42% vs. 14% (p < 0.001). The six month follow-up of tSAH patients complying with the study protocol and treated with intravenous nimodipine, 2 mg per hour for 7 days, showed a statistically significant reduction of unfavourable outcome from 66% to 51% (p < 0.05), compared to placebo treated patients. PMID- 7998487 TI - Cavernous angiomas of the internal auditory canal. A case report and review of literature. AB - Cavernous angiomas of the internal auditory canal (IAC) are rare. They are angiographically occult; and because the clinical symptoms are similar both in intracanalicular cavernous angiomas and acoustic tumors it had been difficult to differentiate pre-operatively both of these pathologies until the advent of magnetic resonance imaging (MRI). Even nowadays the correct diagnosis may be missed if the patient is imaged only with gadolinium enhanced MRI without prior obtaining a non-contrast MRI. These diagnostic difficulties are illustrated by the report of a related case. The importance of thorough neuroradiological investigations stressed and MRI features, surgical management and relevant literature concerning the cavernous angiomas of the internal auditory canal are discussed. PMID- 7998489 TI - Role of skull radiography in the initial evaluation of minor head injury: a retrospective study. AB - The use of skull radiography in the initial evaluation of minor head injured patients is controversial. In an attempt to evaluate its benefits, a retrospective study of 566 cases subjected to skull radiography following close minor head trauma (Glasgow Coma Scale 13-15), is presented. A skull fracture (linear vault, depressed or base of skull) was present in 64 (11%) cases. Only three (5%) who were found to have a skull fracture on skull radiography developed an intracranial injury which required surgery. Intracranial injuries developed in 19 (3%) cases and were followed by surgery in six (32%). All, except for one case, had a decreased level of consciousness and a Glasgow Coma Scale less than 15, few had focal neurological deficits. Management had not been altered by the results of skull radiography in any of the cases. We concluded that skull radiographs are unnecessary for the decision process in closed minor head injury because management decisions are based primarily on a careful neurological examination. When intracranial injuries are a concern, a CT scan should be obtained. PMID- 7998488 TI - Intraosseous calvarial meningioma of the skull presenting as a solitary osteolytic skull lesion: case report and review of the literature. AB - Intraosseous calvarial meningiomas, defined as meningiomas confined to the skull with no epidural or subcutaneous component, are rare and usually exhibit osteoblastic activity. We present a case of a primary intraosseous meningioma in the right frontal bone that presented radiologically as a solitary lytic skull lesion and was completely excised. The lesion was benign without recurrence for 1 1/2 years. According to our review of the literature, our case is the first with documentation on computed tomography. In cases of solitary osteolytic skull lesions, meningioma should be considered even though it may not seem likely, because management will be directed to radical excision with good prognosis rather than biopsy. PMID- 7998490 TI - Avoidable factors that contribute to complications in the surgical treatment of chronic subdural haematoma. AB - The results of a personal series of 44 consecutive patients undergoing burrhole evacuation and closed system suction drainage for chronic subdural haematoma are presented. 43 patients made a complete recovery and one was left with moderate disability. Contralateral weakness in one patient, recurrence of haematoma in another, and a new contralateral haematoma in a third were the only complications. The operative procedures responsible for the rather low complication rate in this series are described. It is concluded that to avoid complications following surgical treatment of chronic subdural haematoma, attention must be paid to the following factors: evacuation of the haematoma through two burrholes overlying the subdural collection; attention to ensure free communication through the subdural space between the two burrholes; identification and opening of additional loculations overlying the cortex; irrigation of the subdural space to ensure as complete an evacuation of the subdural collection as possible and the use of closed system suction drainage, nursing the patient flat, and intravenous hydration of the patient for three days. In addition, in patients with coagulopathy, correction of these disorders before surgery is most essential. PMID- 7998491 TI - Platelet-activating factor (PAF) and the development of chronic subdural haematoma. AB - Platelet activating factor (PAF) content and PAF-acetylhydrolase (PAFAH) activity were measured in the plasma and haematoma of 34 chronic subdural haematoma (CSH) patients. The plasma PAF level in patients with CSH was higher than that in healthy controls. Although there was no correlation between the plasma PAF levels and the interval between the onset of symptoms and the day of sampling, namely, the interval after bleeding, the haematoma PAF level gradually decreased according to the interval after the onset of symptoms. There was no difference between plasma PAFAH activity in patients with CSH and that in healthy controls, and haematoma enzyme activity gradually increased correlated with the interval between the onset of symptoms and surgery. In addition, the localization of PAF in haematoma capsules was histochemically determined. PAF was solely localized to the peri-sinusoidal vessels in the outer membrane of haematoma capsules. Based on these biochemical and histochemical studies, we speculated that PAF may play a role in the development of chronic subdural haematomas. PMID- 7998492 TI - Meningiomas of the anterior cranial fossa floor. Review of 67 cases. AB - The authors report 67 cases of meningioma of the anterior cranial fossa floor treated surgically between 1978 and 1992. The olfactory groove and tuberculum sellae were the most frequent locations. Mean duration of the clinical history was 30 months. Seventy-three percent of the tumors were large (> 4 cm). All patients were examined with computed tomography and 18 with magnetic resonance imaging as well. Complete removal was performed in 56 cases (84%); in the remaining 11 (16%), partial removal was performed because of encasement of the carotid artery, cavernous sinus, or optic nerves by the tumour. Mortality was 9%. Results at follow-up of the 61 survivors were good in 56 (84%), fair in four (6%), and poor in one (1%). The clinical results were correlated to tumor location and dimension. After review of the literature, the management of these difficult tumours and the preferred surgical technique are discussed. The authors stress the importance of early diagnosis for improving the surgical results. PMID- 7998493 TI - Meningiomas associated with peritumoural venous stasis: three types on cerebral angiogram. AB - Many factors have been suggested as possible mechanisms for the development of peritumoural oedema in meningioma. Venous compression by the tumor is thought to be one factor, but reports presenting a direct relationship between venous compression and the formation of oedema are rare. We have recently observed 6 meningioma patients in whom venous stasis contributed to peritumoural oedema. The stasis was due to 1) compression of an adjacent cortical vein by the tumour with stasis at the site of compression and/or its distal portion, 2) compression of adjacent brain by the tumour with prolonged perfusion and delayed venous return (visualized as pial staining in the capillary and venous phases), and 3) presence of an early draining vein linked to a nearby cortical vein with stasis at its periphery. Venous compression and stasis seem to be related not only to the formation of peritumoral oedema but also to the occurrence of haemorrhagic infarction after the resection of meningiomas. PMID- 7998494 TI - Meningiomas: correlation between MRI characteristics and operative findings including consistency. AB - The findings on magnetic resonance imaging (MRI) in 73 surgically verified intracranial meningiomas were correlated with their histology and consistency during resection. T 1-weighted imaging was least useful since most of the tumours were iso-intense, similar to cortical grey matter regardless of histology or tumour consistency. The signal intensity on T2-weighted images was found to best correlate with both the histology and consistency of the meningioma. Generally, the low intensity portion of the tumour on T2-weighted images indicated a more fibrous and harder character, while the higher intensity portions indicated a more soft character. Most of the fibroblastic meningiomas showed the features of a hard tumour while angioblastic tumours showed the features of soft tumours. Tumours predicted to be harder on MR imaging generally took longer to resect than softer ones, and this relationship was shown best for the larger tumours. Using linear regression analysis, it appears that operative time for soft tumours is more affected by factors other than tumour consistency. Blood loss during surgery was also unrelated to the consistency of the tumour. These results suggest that the histology and consistency of meningiomas may be predictable from findings on T2-weighted imaging, and this may also predict the difficulty and time required for resection. PMID- 7998495 TI - Plate and screw fixation for atlanto-axial subluxation. AB - Our experience with 30 cases of atlanto-axial dislocation, over the period of 3 years and 9 months, is described. A modified plate and screw method of fixation of the lateral masses of the atlas and axis was successfully used in these cases. The technical aspects and merits of the method, wherein a 100% union rate was achieved, with no morbidity, mortality, or instrument fatigue or failure, are presented. The average follow-up period is of 19 months. The technique provided immediate rigid segmental internal fixation, permitting early mobilization with minimal external support. Onlay and interfacetal bone grafts subsequently produced bony fusion. Direct application of screws to the atlas and axis, thus utilizing the firm purchase in their thick and large cortico-cancellous lateral mass, provides a biomechanically strong fixation of the region. Occipito-cervical fusion can be achieved in selected cases by a modification of the method. It appears that such a method of fixation could be useful at least in some complex congenital or traumatic craniovertebral region instability where the conventional methods have failed or are not suitable. PMID- 7998496 TI - Iliac crest versus artificial bone grafts in 250 cervical fusions. AB - Autologous (149 patients) and heterologous (101 patients) bone grafts were used for fusion in 250 patients with anterior cervical surgery. A stable fusion was achieved in 98% of patients in both groups and there was no significant difference in the clinical outcome. Donor site complications (severe pain, haematoma) were seen in one sixth of the patients with autologous bone grafts. If a fusion for anterior cervical surgery is necessary, the use of a heterologous bone graft should be preferred. PMID- 7998497 TI - Neuropathological endpoints in experimental stroke pharmacotherapy: the importance of both early and late evaluation. AB - This study addresses the issue of endpoint selection in the evaluation of neuroprotective drugs in experimental focal ischaemia. Previous work with the permanent middle cerebral artery (MCA) occlusion model in the rat has demonstrated that the ischaemic lesion does not acquire its final appearance until at least 28 days after the ictus. Therefore, the effect of the NMDA receptor blocker MK-801 (dizocilpine maleate) was evaluated both early (3 days) and late (28 days) after MCA occlusion to determine if the previously reported protective effect of a single post-ischaemic dose of MK-801 found in acute experiments remained after 28 days. Mk-801 (0.5 mg/kg, i.v.) or isotonic saline was randomly given to rats 30 min after MCA occlusion. Infarct volume and volume of ipsilateral and contralateral hemispheres were estimated from camera lucida drawings of 8 defined coronal histological sections of the brain. As expected, a 40% (p < 0.05) reduction of infarct size was found in MK-801 treated rats after 3 days. In animals evaluated 28 days after MCA occlusion, no significant difference in infarct size, total tissue loss (infarct volume+ipsilateral hemisphere atrophy) or remaining non-infarcted tissue (contralateral hemisphere--total tissue loss) was seen between the MK-801 and placebo treated rats. The results suggest that the single dose treatment with MK-801 postponed the evolution of the infarct, which at 3 days after MCA occlusion is still in progress, possibly by ameliorating oedema formation. It remains to be shown if a multiple dose treatment with NMDA receptor antagonists improves the final neuropathological outcome after experimental stroke.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7998498 TI - Evacuation of traumatic intracerebral haematomas using a simplified stereotactic procedure. AB - The authors present a series of 37 traumatic intracerebral haematomas (ICH) evacuated by a simplified stereotactic surgical procedure. The mortality rate was 80% in patients with Glasgow coma scale (G.C.S.) scores of 3-5 and 25% in patients with scores of 6-7. There were no deaths in patients with G.C.S. of 8 or more. With the exception of the first group of patients, the results were better than those achieved by wide craniotomy. The importance of reduced operative trauma in patients with ICH, which often are associated with multifocal or diffuse brain injuries, are discussed. PMID- 7998499 TI - Effect of nerve growth factor on delayed neuronal death after cerebral ischaemia. AB - We investigated the protective action of nerve growth factor (NGF) on delayed neuronal death, and we also studied the involvement of the 200 kDa neurofilament (NF200) cytoskeletal proteins. Wistar rats were divided into three groups: Group I, in which transient forebrain ischaemia was produced; Group II, ischaemic group which received intraventricular administration of artificial cerebrospinal fluid (CSF); and Group III, ischaemic group which received intraventricular administration of 2 micrograms of 2.5 S NGF. Forebrain ischaemia in these rats was produced by causing transient bilateral occlusion of the common carotid arteries and lowering the mean blood pressure to 50 mmHg for 8 minutes. On the 1st and 7th day after ischaemia we histologically examined neuronal death in the hippocampal CA 1 sector. On the 7th day after ischaemia, mean cell death (degenerative cell number/total cell number) was 87 +/- 9% in group I (n = 7), 51 +/- 36% in group II (n = 7), and 14 +/- 16% in group III (n = 8) (p < 0.05 vs. group II). The concentration of NF200 in the hippocampal homogenate was measured by the Western blotting method on the 1st and 7th day after ischaemia. On the 1st day it was found to be 67 +/- 11% of that in the control group in group I (n = 6), 73 +/- 21% in group II (n = 6), and 84 +/- 7% in group III (n = 6) (p < 0.05 vs. group II). The concentration of NF200 in all groups remained at the same level until the 7th day after ischaemia (each group, n = 6).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7998501 TI - A stereotactic guide for microsurgery. Technical note. AB - A stereotactic guide for microsurgery is presented. The guide consists of a weak helium neon laser projecting a red beam towards the target when the arc carrying the beam has been set on the Leksell frame according to the stereotactic co ordinates of the target calculated on the pre-operative imaging studies. The device allows free manoeuverability of the operating microscope. PMID- 7998500 TI - Verification of the Schaltenbrand and Wahren stereotactic atlas. AB - The Schaltenbrand and Wahren stereotactic atlas was critically re-examined focusing on the technical quality and the consistency of the horizontal, sagittal and frontal microscopic cut series. From each series, both an isotropic contour and a solid volume model represented by a 256 matrix with an edge length of 6.4 cm were created using 3D-interpolation. Reslicing of the solid volumes in corresponding orthogonal planes enabled thorough direct comparison of the three series. In a 3D-navigation system prototype, the contour models can be matched to MRI and CT series. Different procedures for rigid matching including landmark matching were implemented. As regards the verification criteria, the frontal Schaltenbrand and Wahren series yielded the most comprehensible results whereas in the horizontal and sagittal series artifacts appear more pronounced. PMID- 7998502 TI - Ventriculoscope-guided ventriculoperitoneal shunt and shunt revision. Technical note. AB - A new small, flexible fiberoptic ventriculoscope for the accurate positioning of a ventricular catheter tip has been developed. The technique for ventriculoscope guided ventriculoperitoneal shunt and shunt revision is described. The ventricular catheter can easily be positioned away from the choroid plexus. Choroid plexus adhering to the shunt tube can be coagulated during shunt revision. This procedure can thus prevent an obstruction of the ventricular catheter by an adherent choroid plexus. PMID- 7998503 TI - Stereotactic biopsy for intrinsic lesions of the medulla through the long-axis of the brainstem: technical considerations. AB - The authors report the technique and results for stereotactic biopsy of intrinsic lesions of the medulla oblongata through the long-axis of the brainstem. Multi planar stereotactic magnetic resonance imaging and/or reformatted computed tomography imaging is used for coordinate determination and trajectory selection and facilitates a completely intra-axial pathway through critical neural tissue. Two patients with small, solitary, enhancing lesions of the medulla had stereotactic sampling via this approach performed under local anesthesia. There was no morbidity and in both the patients a histologic diagnosis of lymphoma was obtained. We believe that with high-resolution, multi-planar stereotactic imaging, small lesions in the medulla can safely be biopsied, avoiding the need for either posterior fossa craniectomy and open biopsy, or for empiric management. PMID- 7998504 TI - Halo ring supporting the Brown-Roberts-Wells stereotactic frame for fractionated radiotherapy. AB - The authors describe a new instrumentation for repositioning of the Brown-Roberts Wells (BRW) stereotaxic system, useful for precise fractionated radiotherapy. A lucite ring is fixed to the patient's skull with four screws. Another ring, partially open, is then firmly connected co-axially to the lower part of the first one with four spacer-bars. The fixture permits an exact repositioning of the B.R.W. stereotaxic system, placing the target point in the linear accelerator isocenter. The preliminary technical results obtained in five children are reported and the fixture performance, advantages, and perspectives are discussed. PMID- 7998505 TI - A newly designed attachment device of multipurpose frame for neuronavigator. Technical note. AB - A newly designed attachment device of the multipurpose head frame (Sugita) for Neuronavigator (Watanabe) is presented with an illustrative case of glioblastoma in an eloquent area. This has extended the usefulness of the neuronavigator for those who prefer and use the multipurpose head frame, while the requirements for keeping a stereotactic combination and the original concept of the multipurpose head frame, as well as that of the neuronavigator have been kept undisturbed. PMID- 7998506 TI - [Urologic emergencies: our difficult experience with care services]. AB - Urological emergencies, except those occurring in children, seen in a General Hospital were studied for one year. The retrospective study, both descriptive and comparative, conducted has allowed to know that there had been 3,244 emergencies (4.2% of total cases) though the urologist acted only in 1,410 (43.4%). A predominance of males (76.10%) in their sixth and seventh decade (33% of total) was seen. Presentation increased slightly (2%) above average during the summer months. 80.9% came to the Emergency Ward of their own accord and 70% were discharged soon after assistance. Nephritic colic (19.08%), haematuria (14.04%) and U.T.I. (13.83%) were the most common causes for presentation. A total of 284 patients (20.14%) required hospitalization. 96.6% were given medical and/or instrumental treatment, versus 3.4% (49) who underwent surgery basically due to testicular disease (34.69%), sepsis (24.50%), traumatic injury of male genitalia (20.3%), etc. The most frequent conditions were analyzed by age, sex, and seasonal distribution. Also, an analysis was made on the concept of "Urological Emergency" to evaluate incidence and types in our environment. PMID- 7998507 TI - [Transitional carcinomas of the urinary tract: synchronous and metachronous lesions]. AB - OBJECTIVE: The urothelium is a pseudostratified cylindrical epithelium that lines the calices, renal pelvis, urethers, bladder, part of the urethra and part of the prostate ducts. Transitional cell carcinoma (TCC) is a malignant neoplasia that can appear in any site where urothelium is present, being the bladder the most frequently affected organ. We performed an analysis of our experience and conducted a literature-based metanalysis to evaluate the coexistence of tumoral lesions at different locations in the urinary tract. MATERIAL AND METHODS: Between 1983 and 1993, 397 patients with TCC lesions involving the upper urinary tract (UUT), bladder, urethra or prostate, were diagnosed and treated. Coexistence, either synchronic or metachronic, of several lesions in different sites of the urinary tract was considered as a multiple tumor. RESULTS: Overall, 440 tumors were diagnosed in 397 patients. A single lesion appeared in 360 patients, while 37 presented multiple locations with a total of 79 tumors. The lesions were located at the following levels: 17 renal, 21 uretheral, 372 vesical, 13 in the urethra and 17 in the prostate ducts. According to the location, the frequency of single lesions was: UUT 58%, bladder 91%, urethra 8% and prostate ducts 35%. Synchronic UUT and intravesical tract tumors develops in 1% and 4% of patients with bladder TCC, respectively. Two percent of vesical tumors showed metachronic relationship with UUT tumors and the same rate was seen for intravesical lesions. CONCLUSIONS: Urothelial UUT tumors have a typical nosologic entity with specific features. Their coexistence with vesical tumors is frequent. When tumors of the bladder occur after a UUT tumor the interval of highest incidence between diagnoses is 2-3 years, and there are no histological risk factors among them for prognosis. Transitional cell prostatic urethral tumors are most often secondary to histologically similar, poor prognosis, bladder tumors, and usually synchronic. PMID- 7998508 TI - [Malignant neoplasms and kidney transplantation]. AB - In 661 renal transplantations, 2 potentially migrated tumours (0.38%), 5 preexisting neoplasias (0.76%), and 31 "de novo" tumours were seen in 29 patients (4.4&). Although of very low incidence, the likelihood of tumour migration from elderly donors, given the circumstances surrounding removal, offers a high risk. None of the preexisting neoplasias relapsed following transplant. The highest prevalence was seen in skin (40%), lung (13%), kidney (13%) and bladder (6.6%) "de novo" tumours. Incidence of lymphoma was low. Dominant etiological factors of the recipient were older age, effective and tolerated immunosuppression, viral infections, environmental agents and antigenic stimulation of the graft. Skin lesions have responded well to local treatment, without need to discontinue immunosuppression, a measure that is mandatory in other malignant tumours. Also, the conclusions of a round table during the 25th National Meeting of Urotransplantation of the Spanish Association of Urology held in 1994 on "Oncology and Renal Transplantation" are presented. PMID- 7998509 TI - [Paratesticular rhabdomyosarcoma in children. Is retroperitoneal lymphadenectomy necessary in disease limited to the scrotum?]. AB - Between 1970 and 1993, five children with paratesticular rhabdomyosarcoma (PR) and age ranging from 3 to 10 years were treated by our group. Following radical orchidectomy and clinical staging, 4 were rates as Group I-IRS (completely resected local disease) and 1 in Group IV-IRS (distant metastasis). All patients in Group I underwent intensive chemotherapy with vincristine, actynomicin D and cyclophosphamide (VAC) for 18 months, while no case of retroperitoneal lymphadenectomy was performed. Currently, all patients are disease free with a mean follow-up of 8 years and 5 months. The single patient included in Group IV received radiotherapy (800 rads in abdominal field) and chemotherapy with VAC + prednisone (PDR), and retroperitoneal lymphadenectomy of residual masses was performed. The patient developed liver metastasis and died 20 months later. The purpose of this paper is to convey the reader our experience in the treatment of PR in children, making a special reference to the excellent prognosis when the disease is limited to the scrotum and recommending in such cases the use of intensive chemotherapy with VAC after performing radical orchidectomy. PMID- 7998510 TI - [Keratinizing squamous metaplasia (cholesteatoma) of the upper urinary tract]. AB - Presentation of four cases of keratinizing squamous metaplasia (KSM), two of the renal pelvis, one pyelocaliceal and one ureteral. Nephrouretetectomy was performed in all cases. All our patients showed good evolution. A review of the literature is made discussing all the etiological, diagnostic and therapeutical aspects of the condition. Its benign evolution is highlighted as well as the current need, once a better knowledge of the condition's natural history is available, of using a conservative approach. PMID- 7998511 TI - [Renal leiomyoma. Report of a new case]. AB - Though renal leiomyoma is an unusual tumour, symptomatic tumours are even more uncommon. They often raise problems with differential diagnosis from malignant tumours which not even the most advanced imaging techniques manage to elucidate. On the other hand, their sarcomatous degeneration has been described. Considering these premises, doubts arise on their therapeutical approach, on which we here present our own views. PMID- 7998513 TI - [Ureteral endometriosis. Report of a case]. AB - Presentation of one case of ureteral tumour with the patho-anatomical label of intrinsic multifocal endometriosis, who underwent surgical treatment. Endometriosis is a clinic-gynaecological problem affecting 10-20% of pre menopausal women. The urinary tract compromise happens in 1-10% of women with endometriosis. In spite of being an uncommon pathology, early diagnosis is of great importance due to the large number of non-saveable kidneys that it causes (25-43%). In our opinion, in cases with established fibrosis we regard surgery as the choice therapy. A presentation is made of the clinical case, pathological anatomy, treatment and comments on the disease. PMID- 7998512 TI - [Osteoblastic differentiation in primary renal tumor: a rare histologic finding]. AB - Presentation of one case of renal carcinoma which interest lies in the osteoblastic differentiation presented by the sarcomatoid component. The rarity of this tumour type in major series of sarcomatoid renal carcinomas published is emphasized. Also, a description of its most relevant singularities is made. PMID- 7998514 TI - [The nutcracker phenomenon: an infrequent cause of hematuria]. AB - The nutcracker phenomenon consists in the compression of the left renal vein by the aortomesenteric clamp. This is an infrequent cause of haematuria. The present paper presents one case of nutcracker phenomenon showing haematuria after mild accidental lumbar bruising, with arteriographic diagnosis. CAT assessment showed a mark in the lumbar ureter as well as peripyelic and periureteral varices. PMID- 7998515 TI - [Spontaneous bladder rupture secondary to urinary tuberculosis]. AB - Atraumatic spontaneous vesical fracture is an uncommon occurrence. Here we present the case of a female patient with spontaneous vesical fracture secondary to urinary tract tuberculosis. A review of current literature showed another published case similar to ours. A brief comment is made on presentation signs and symptoms and picture evolution, as well as a discussion on the predisposing factors of spontaneous vesical fracture and its treatment. PMID- 7998516 TI - [Malignant fibrohistiocytoma coexisting with papillary tumor of the kidney pelvis: report of a case]. AB - Presentation of one case of malignant fibrohistiocytoma in one patient seen for gross clotting haematuria during the study of which the coexistence of this tumour with a renal pelvis papillary one was discovered. The disease's clinical and diagnostic aspects are commented, with special emphasis on histological diagnosis. A review of the existing literature is also made. PMID- 7998517 TI - [Emphysematous pyelonephritis]. AB - Presentation of one case of emphysematous pyelonephritis, an unusual entity usually affecting diabetic women with obstruction of the upper urinary pathways, all of which are conditions present in our patient. Death rate of this disease is high, requiring emergency surgical/endourological approach with appropriate antibiotic coverage. PMID- 7998518 TI - [Abdomino-scrotal hydrocele, an unusual disease, review of the literature, and report of a new case]. AB - Abdominal-scrotal hydrocele is an uncommon lesion, most specially during childhood. It is an entity, though, that should be included in the differential diagnosis of abdominal masses in children, and also considered as a likely cause of ureterohydronephrosis. Diagnosis is arrived at through ultrasound, CAT and occasional excretory urography. Radical surgical excision using inguinal access is the recommended approach, but sometimes the inguinoabdominal or pure abdominal approaches can be performed. Following surgical ablation the cure is complete, and includes remission of the ureterohydronephrosis when present. This paper reviews the literature, presents one case and discusses both the diagnostic possibilities and therapeutic alternatives. PMID- 7998519 TI - Merrill C. Sosman Lecture. MR imaging of the wrist. AB - Imaging of the wrist should always begin with a plain film examination. Sonography and tenography are sometimes used to evaluate tendon abnormalities. Sonography is operator dependent; tenography, because of its invasive nature, is rarely used today. Arthrography, with single or triple injection techniques, with [1] or without [2] digital subtraction, has been the procedure of choice for detecting abnormalities of the interosseous ligaments and the triangular fibrocartilage (TFC). MR imaging is the only imaging technique that can directly depict the interosseous ligaments and the TFC. It is the imaging technique of choice for the early diagnosis of aseptic necrosis, for tumor staging, and for evaluating soft-tissue masses. MR imaging enables noninvasive global examination of the wrist that is extremely sensitive in detecting osseous and soft-tissue disease. Because technical advances will allow more rapid data acquisition, thinner slices, and higher resolution, I predict MR imaging will replace arthrography in the near future. PMID- 7998521 TI - Variations in the intrahepatic portions of the hepatic and portal veins: findings on helical CT scans during arterial portography. AB - OBJECTIVE: The goals of this study were to describe variations in the intrahepatic portions of the hepatic and portal veins as visualized by helical CT during arterial portography (CTAP) and to examine the surgical implications of these findings. MATERIALS AND METHODS: A retrospective review of 69 helical CTAP scans of 69 patients with small hepatic tumors and no evidence of vascular invasion or distortion was done. Axial helical CTAP scans were reviewed to determine the presence, number, and location of intrahepatic portions of the hepatic and portal veins. RESULTS: Among the 60 patients (87%) in whom the right, middle, and left hepatic veins were visualized, 19 (32%) had supernumerary hepatic veins. Right inferior hepatic veins were found in six (9%) of the 69 patients. Variations in intrahepatic portal anatomy were found in four patients (6%) and involved an immediate trifurcation of the portal vein in three patients (4%) and a left main portal vein originating from the right anterior portal branch in one patient (2%). CONCLUSION: Variations in the intrahepatic portions of the hepatic and portal veins are frequently seen on helical CTAP scans. Recognition of such variations is important in the preoperative evaluation of patients with hepatic tumors because these variations may have implications for tumor resection and for planning the operative approach. PMID- 7998520 TI - Anshutz on anatomy. PMID- 7998522 TI - Staging urinary bladder cancer: value of T1-weighted three-dimensional magnetization prepared-rapid gradient-echo and two-dimensional spin-echo sequences. AB - OBJECTIVE: The purpose of this study was to evaluate a magnetization prepared rapid gradient-echo (MP-RAGE) sequence as a three-dimensional T1-weighted MR imaging technique for staging urinary bladder cancer and to compare this technique with a commonly used two-dimensional T1-weighted spin-echo sequence technique. SUBJECTS AND METHODS: For 28 consecutive patients with urinary bladder cancer, MR findings and staging results were compared with histopathologic findings after surgery or autopsy. MR imaging was performed at 1.5 T with a Helmholtz double-surface coil. Conventional T1-weighted spin-echo, three dimensional MP-RAGE, T2-weighted spin-echo or turbo-spin-echo, and dynamic T1 weighted fast gradient-echo sequences were used. Signal difference-to-noise ratios and T1 contrast were calculated by use of operator-defined regions of interest. RESULTS: The signal difference-to-noise ratios for fluid-tumor and fat tumor were, respectively, factors of 1.6 and 2.7 better with T1-weighted spin echo sequences. T1 contrast of fluid-tumor was a factor of 2.6 better with three dimensional MP-RAGE sequences, resulting in better recognition of small tumors, ascites, and dilated ureters. T1 contrast for fat-tumor was a factor of 2.0 better with T1-weighted spin-echo sequences. With the MP-RAGE sequence, motion artifacts were fewer in number than those noted with the T1-weighted spin-echo sequence, and susceptibility artifacts were equal in number to those noted with the T1-weighted spin-echo sequence. Using the three-dimensional technique, we performed off-line reconstruction of 1- to 2-mm high-resolution images in every desired plane. Because of higher spatial resolution, the availability of multiplanar reconstructions, and better fluid-tumor contrast and despite lower signal difference-to-noise ratios, three-dimensional MP-RAGE images resulted in better recognition of local tumor extension (n = 11), adhesions and bowel wall invasion (n = 5), lymph node metastases (n = 2), and bone marrow metastases (n = 2). The staging accuracy for the combination of three-dimensional MP-RAGE, T2 weighted, and dynamic sequences was 93%; that for the combination of two dimensional T1-weighted spin-echo, T2-weighted, and dynamic sequences was 78%. Nodal staging was also more accurate with MP-RAGE sequences (accuracy of 93% vs 86% for T1-weighted spin-echo sequences). CONCLUSION: Compared with two dimensional T1-weighted spin-echo imaging, three-dimensional MP-RAGE imaging resulted in a 15% improvement in staging. Our findings suggest that optimal staging of urinary bladder carcinoma requires three-dimensional imaging techniques. PMID- 7998523 TI - Evaluation of the renal arteries in kidney donors: value of three-dimensional phase-contrast MR angiography with maximum-intensity-projection or surface rendering. AB - OBJECTIVE: Donors routinely undergo preoperative conventional arteriography to evaluate the renal arteries before nephrectomy. The purpose of this study was to assess the capability of three-dimensional phase-contrast MR angiograms postprocessed with maximum-intensity-projection and surface-rendering techniques to show the renal arteries of potential donors. MATERIALS AND METHODS: Postprocessed three-dimensional phase-contrast MR angiograms of 17 patients were retrospectively reviewed by two experienced radiologists for the number and length of renal arteries visualized. Conventional arteriograms were used as the reference standard. Coronal maximum-intensity-projection and surface-rendered MR angiograms were also compared with each other with regard to the delineation of renal arteries from overlapping vessels. RESULTS: MR angiograms showed all 34 single or dominant renal arteries but only eight of 10 accessory arteries seen on conventional arteriograms. One of the nonvisualized accessory arteries was located within the imaged volume, and the other one arose from the distal aorta beyond the imaged regions. Five of six arterial branches arising from the proximal 30-mm portions of the renal arteries were seen on MR angiograms. Postprocessing with either maximum-intensity projection or surface-rendering showed the same number of renal arteries, although surface rendering separated overlapping veins from the renal arteries better than the maximum-intensity projection technique. CONCLUSION: These results suggest that three-dimensional MR angiography is a reliable method of imaging single or dominant renal arteries, but not for showing all accessory renal arteries and small arterial branches. Surface rendering may provide specific advantages over maximum-intensity projection in delineating renal arteries from overlapping vessels. PMID- 7998524 TI - Prostatic and periprostatic cysts: findings on MR imaging. AB - Cysts of the prostate or perioprostatic tissues are uncommon and include congenital mullerian or utricular cysts, prostatic retention cysts, cysts of benign prostatic hyperplasia, cystic carcinoma, parasitic and infectious cysts, as well as cysts of the ejaculatory apparatus or seminal vesicles. The radiological diagnosis of prostatic or periprostatic cysts can be difficult because of the resolution needed to define the relationship of a cyst to surrounding structures, such as the vas deferens, seminal vesicles, and ejaculatory ducts [1]. Prostatic cysts are easily identified on MR images by virtue of their high signal on T2-weighted images and can be characterized because of their typical locations and the high resolution and multiple imaging planes provided by MR [2]. Because these conditions are usually managed conservatively, pathologic proof is not possible in all cases, and the diagnosis is often made on the basis of clinical features and imaging appearance. The purpose of this essay is to illustrate the findings on MR imaging. PMID- 7998525 TI - Malignant soft-tissue tumors in a large referral population: distribution of diagnoses by age, sex, and location. AB - OBJECTIVE: The purpose of this study was to determine the relative prevalence, age at presentation, sex distribution, and skeletal distribution of malignant soft-tissue tumors and to ascertain the relative frequency of these tumors in specific anatomic locations and age groups among a population of patients in a large pathologic consultation service. MATERIALS AND METHODS: The computer diagnoses of 39,179 lesions occurring in 38,484 patients seen by soft-tissue pathologists at the Armed Forces Institute of Pathology during the 10-year period from January 1, 1980, to December 31, 1989, were retrospectively reviewed. All lesions were placed in one of 121 major categories in accordance with the classification system used by the World Health Organization and coded to one of 32 anatomic locations, such as hand, wrist, forearm, and so forth. Age and sex also were recorded. For purposes of analysis, all lesions were placed in one of 10 categories: hand and wrist, upper extremity, proximal limb girdle (axilla and shoulder), foot and ankle, lower extremity, hip and buttocks region, head and neck, trunk, retroperitoneum, and other lesions. The study group included 31,047 mesenchymal lesions, of which 12,370 were malignant. RESULTS: More than 80% of malignant tumors were classified into eight diagnostic categories: malignant fibrous histiocytoma (24%), liposarcoma (14%), leiomyosarcoma (8%), malignant schwannoma (6%), dermatofibrosarcoma protuberans (6%), synovial sarcoma (5%), fibrosarcoma (5%), and sarcoma, not classified further (12%). Approximately 79% of all malignant tumors were classified into five diagnoses for each age and location. With the distal upper extremity (hand and wrist) as an example, 50% of malignant lesions in the 16-25-year-old group were classified as epithelioid sarcoma (29%), malignant fibrous histiocytoma (13%), and synovial sarcoma (8%). For the same location but for children 5 years old or younger, almost 50% of malignant tumors were classified as infantile fibrosarcoma. CONCLUSION: Despite the multitude of pathologic possibilities, most malignant soft-tissue tumors are classified into a small number of diagnoses. These may be further defined when the location of the lesion and the age of the patient are considered. Knowledge of tumor prevalence will assist radiologists in establishing a suitably ordered differential diagnosis when a soft-tissue tumor has a nonspecific radiologic appearance. PMID- 7998526 TI - Complete dislocation of the knee: spectrum of associated soft-tissue injuries depicted by MR imaging. AB - OBJECTIVE: Complete knee dislocation is a rare injury. The purpose of this study was to evaluate the spectrum of injuries that are depicted by MR imaging in patients with a dislocation of the knee and to determine if there is any predictive factor that might indicate those patients who may be at risk for popliteal nerve injury. MATERIALS AND METHODS: A retrospective search for patients sustaining traumatic knee dislocations who had radiographs and an MR imaging examination of the knee as part of their initial evaluation was done at three level I trauma centers for the period between 1989 and 1993. Each MR examination was independently reviewed by three osteoradiologists for ligamentous, tendinous, meniscal, and osseous injuries. Equivocal diagnoses were decided by consensus. Only patients who underwent surgery were selected. MR imaging findings were confirmed at the time of surgery. Seventeen patients (15 men, two women; age range, 14-62 years; mean age, 29 years) were studied. Motor vehicle accident, fall from a height, a vehicle striking a pedestrian, and football injury were common mechanisms of injury. Posterior dislocation (seven patients) and anterior dislocation (five patients) were the most common injuries. RESULTS: At the time of surgery, all patients had complete tears of the anterior cruciate ligament, 15 had complete tears of the posterior cruciate ligament, nine had complete tears of the medial collateral ligament, and 12 had tears of the fibular collateral ligament (nine tore both the fibular collateral ligament and the biceps femoris tendon). Popliteal tendon tears occurred in eight patients (six complete, two partial). Of the six patients with complete tears of the popliteal tendon, five occurred at the musculotendinous junction; all were the result of either posterior or posterolateral dislocations. Four patients had injuries to the peroneal nerve; three of the four also had tears of the popliteal tendon. On MR imaging, the integrity of the anterior cruciate and lateral collateral ligaments was correctly depicted in all 17 patients; evaluation of the posterior cruciate ligament resulted in one false-positive and one false-negative diagnosis of a tear; evaluation of the medial collateral ligament resulted in one false-positive diagnosis of a tear; and one false-positive diagnosis of a tear occurred with evaluation of the popliteal tendon. CONCLUSION: Knee dislocations cause extensive disruption of the ligaments that stabilize the knee and the surrounding soft-tissue structures, including the popliteal artery. Nearly all will result in disruption of the cruciate ligments and, often, injury of the collateral ligaments. An injury to the popliteal tendon denotes a more severe injury. The mechanism of injury that results in a popliteal tendon tear may also increase the possibility of a peroneal nerve injury. Recognition of this pattern of injuries on MR imaging enables precautionary observation for ischemic changes of the foot to be instituted in patients that otherwise may not be considered at risk for acute vascular compromise. PMID- 7998528 TI - Preoperative assessment of symptomatic bunionette deformity: radiologic findings. AB - A symptomatic bunionette (tailor's bunion) is a painful bony prominence on the lateral side of the fifth metatarsal head, often associated with an inflamed thickened adventitious bursa and hypertrophic keratoses or calluses. The diagnosis is based on the presence of pain that is most often caused by pressure from footwear. The purpose of this essay is to illustrate the radiographic abnormalities of bunionettes and useful angular measurements as they relate to the preoperative evaluation of symptomatic bunionette deformity. PMID- 7998527 TI - MR arthrography of the shoulder: normal intraarticular structures and common abnormalities. AB - MR imaging with gadopentetate dimeglumine (MR arthrography) is a new technique for evaluating the shoulder. Early clinical experience indicates that MR arthrography improves the visualization of intraarticular structures [1-3]. On T1 weighted images, high-signal contrast solution outlines the low-signal surface of the cuff tendons, the contour of the glenoid labrum, and the course of the glenohumeral ligaments. This essay illustrates the anatomic features of normal glenohumeral structures seen on MR arthrography and common pathologic disorders of the labral-ligamentous complex and rotator cuff. PMID- 7998529 TI - The intracranial venous system in infants: normal and abnormal findings on duplex and color Doppler sonography. AB - Venous hypertension has been implicated as an important factor in the pathogenesis of neonatal brain injury under a variety of circumstances, such as periventricular hemorrhagic infarction in the preterm infant [1], cerebrovascular injury after treatment with extracorporeal membrane oxygenation (ECMO) [2], and thrombosis of the superior sagittal sinus. Although duplex and color Doppler sonographic techniques have been used to evaluate the intracranial arterial tree for several years, little attention has been paid to the role of Doppler techniques in the evaluation of the cerebral venous system. We describe the appearance of the normal infantile cerebral venous system on color and duplex Doppler sonograms and present a spectrum of abnormalities in venous hemodynamics in critically ill infants with the goal of familiarizing readers with the clinical potential of this technique. PMID- 7998530 TI - Gymnast's wrist (pseudorickets growth plate abnormality) in adolescent athletes: findings on plain films and MR imaging. PMID- 7998531 TI - Time-of-flight MR angiography of the brain: comparison of acquisition techniques in healthy volunteers. AB - OBJECTIVE: The saturation phenomenon that limits vessel visibility in unenhanced time-of-flight MR angiograms can be overcome by the injection of MR contrast agents that shorten the T1 of the blood. Unlike the situation with unenhanced MR angiographic acquisitions, in which the MR parameters must be carefully adjusted to reduce saturation effects, optimization procedures for contrast-enhanced MR angiography focus on the acquired shortening of the T1 of the blood and the time evolution of the T1 over the entire measurement. To improve the quality of contrast-enhanced time-of-flight MR angiographic acquisitions in the brain, we compared different acquisition techniques that exploit shortening of the T1 of the blood. SUBJECTS AND METHODS: High-resolution MR angiographic examinations were done with a 1-T MR system for 12 healthy volunteers. Doses of 0.1 and 0.2 mmol of gadopentetate dimeglumine per kilogram of body weight were injected on two separate days to allow for identical timing of the comparative studies after contrast material injection. The effects of dose of contrast material, MR parameters (TR and flip angle), method of injecting the contrast material (monophasic, biphasic, or continuous slow injection), and K-space acquisition schemes (regular schemes versus collecting the central K-space lines near the beginning or the end of the acquisition) were studied. RESULTS: Higher doses provided better MR angiograms. The flip angle and the TR had to be adjusted on the basis of the Ernst equation and therefore depended on an estimation of the averaged T1 value over the entire measurement. Comparison of the different K space acquisition schemes confirmed that the evolution of the T1 of the blood over the entire measurement time is important, especially for longer measurements. There was no noticeable difference between the MR angiograms acquired with monophasic or biphasic injections. These injection schemes provided more detailed MR angiograms than did continuous slow injection over the entire measurement. CONCLUSION: Our results show that the quality of contrast-enhanced MR angiograms can be remarkably increased when acquisition techniques that exploit the short T1 of the blood are used. PMID- 7998532 TI - Combined effects of magnetization transfer and gadolinium in cranial MR imaging and MR angiography. AB - Magnetization transfer (MT) imaging is an MR technique in which image contrast is altered by applying RF pulses that saturate a restricted pool of hydrogen protons associated with cell membranes, proteins, and other macromolecules. Protons in this restricted pool, unlike those in tissue-free water, are not visible on MR due to their short T2 relaxation times. However, these restricted protons modulate the observed signal from free water by dipolar and chemical exchange interactions. In MT imaging, specifically tailored RF pulses are applied to saturate selectively the restricted macromolecular pool. This saturation is "transferred" to the free protons, causing their signal amplitude to decrease [1]. Increased signal intensity due to T1 shortening caused by gadolinium administration does not depend upon macromolecular interactions and is not appreciably suppressed by MT pulses (Fig. 1). Consequently, MT pulses act synergistically with gadolinium to increase the visibility of enhancing lesions by preferentially suppressing nonenhancing background tissue [2]. The purpose of this paper is to demonstrate the principles underlying the synergistic effects of MT saturation and paramagnetic contrast agents and to illustrate these effects in clinical MR imaging and MR angiography. PMID- 7998533 TI - MR myelography: imaging findings. AB - MR myelography, heavily T2-weighted fast spin-echo imaging with fat suppression, enhances the signal intensity of CSF with subtraction of the surrounding background signal. Krudy [1], who first described the technique, used multiple projections per examination. We illustrate the findings in 80 patients who were examined with a modified MR imaging technique that provides increased spatial resolution and uses a single coronal sequence after the conventional MR study. This report illustrates the usefulness of MR myelography in cases of spinal stenosis or spinal block, in both the lumbar and thoracic regions. PMID- 7998534 TI - A CT- and MR-compatible reference marker box for use with stereotaxic frames. PMID- 7998535 TI - CT diagnosis of unsuspected traumatic cataracts in patients with complicated eye injuries: significance of attenuation value of the lens. AB - OBJECTIVE: The purpose of this study was to determine whether the CT attenuation value of the lens is helpful in diagnosing acute traumatic cataracts in patients with complicated eye injuries that preclude evaluation by any other means. SUBJECTS AND METHODS: The CT attenuation values of the lenses of 69 patients with acute orbital trauma, including 24 patients with clinically and surgically diagnosed acute traumatic cataracts, were compared with attenuation values of their own contralateral lens and with the attenuation values of the lenses of 103 consecutive asymptomatic control subjects. The study group was composed of consecutive patients with unilateral orbital trauma who were clinically evaluated and referred for CT examination within 48 hr after their initial injury. In all patients, attenuation measurements of the injured lenses were obtained and compared with those of the contralateral lens as an internal control. All surgically diagnosed cataracts were histologically confirmed. RESULTS: The CT attenuation measurement of a lens in any asymptomatic control subject was identical (within the range of the standard deviation) to the measurement of the contralateral lens of that control patient. In patients with orbital injury, the CT attenuation of the patient's cataractous lens was markedly lower than in the contralateral lens (mean density difference, 30 H, p < .0001). This decreased attenuation corresponds to acute cataract formation with increased fluid within the lens. No patient with normal attenuation values of the lens in the traumatized globe (as compared with the contralateral lens) was found to have an acute traumatic cataract or have a cataract develop within a 1-year follow-up period. CONCLUSION: CT may be useful in the examination of patients with acute traumatic cataracts, unsuspected lens injury, opacification of the anterior chamber, or other injuries of the globe with complications that preclude lens evaluation by any other means. This prompt diagnosis may allow timely removal of the lens in appropriate clinical circumstances, preventing damage to the anterior chamber of the globe and other complications of delayed diagnosis and treatment. Further, normal CT findings at the time of trauma suggest that the lens will not undergo acute traumatic cataract formation. PMID- 7998536 TI - Chronic sinusitis: relationship between CT findings and clinical history of asthma, allergy, eosinophilia, and infection. AB - An interdisciplinary study from the University of Virginia was reported in a recent issue of the Journal of the American Medical Association (JAMA) [1]. The results of that study are pertinent to radiologists who interpret CT scans for patients with chronic sinus disease. The study examined the relationship among eosinophilia, asthma, allergy, and sinusitis and assessed the findings obtained for the paranasal sinuses by high-resolution CT. Soft-tissue disease seen within the paranasal sinuses on CT scans is often described as mucosal thickening or mucoperiosteal thickening, with little attention to its exact nature. The JAMA article showed that for patients properly prepared for sinus CT, the thickened mucosa depicted within the sinonasal cavity is a significant site of functional, immunologically active tissue. The purpose of this article is to bring the findings of the JAMA report to the attention of radiologists and to emphasize the imaging technique, findings, and clinical relevance of the results. PMID- 7998537 TI - Gastropexy breakdown and peritonitis after percutaneous gastrojejunostomy in a patient with ascites. PMID- 7998539 TI - CT percutaneous biopsy guns: comparison of end-cut and side-notch devices in cadaveric specimens. AB - OBJECTIVE: The purpose of this study was to compare the efficacies of four different types of end-cut biopsy guns with the side-notch Tru-cut biopsy gun. MATERIALS AND METHODS: A total of 25 liver, 15 kidney, 10 pancreas, and 15 breast biopsies were performed in the tissue from five autopsies with each of 12 different biopsy devices/biopsy depths. The tissue obtained was evaluated by an experienced cytopathologist who, not knowing which gun was used to obtain each specimen, used a predetermined grading scheme. RESULTS: When tissue was obtained, the end-cut biopsy guns performed equivalently to the side-notch biopsy gun in all four tissues. However, the end-cut guns had a significant number of "zero" biopsies (biopsy attempts during which no tissue was obtained). The proportion of zero biopsies with the end-cut guns ranged from up to 28% in the liver to 60% and 73% in the breast and kidney, respectively. CONCLUSION: The end-cut biopsy guns are easy to use and potentially can obtain high-quality specimens. However, the rate of zero biopsies during which no tissue is obtained is a serious deficiency. As a result, the use of the end-cut biopsy gun should be encouraged only for use with an introducer, with which multiple biopsy specimens can easily be obtained without additional needle punctures. PMID- 7998538 TI - New methods for imaging the breast: techniques, findings, and potential. AB - Mammography is currently the best imaging technique for the early detection and diagnosis of breast cancer. Although numerous advances and improvements in mammography in the past decades have greatly improved image quality, the technique is not without shortcomings that limit its sensitivity and specificity. Multiple areas of research have therefore been sought not only to improve film/screen mammography, but also to consider entirely new techniques in the study of breast cancer. Although this review is not intended to include all methods currently under investigation, those chosen for discussion represent areas where major efforts have provided data that suggest exciting future applications. These include MR imaging, digital mammography, computer-aided diagnosis (CAD), positron-emission tomography (PET), and single-photon emission planar CT imaging (SPECT). PMID- 7998540 TI - Treatment of pelvic abscesses: value of one-step sonographically guided transrectal needle aspiration and lavage. AB - OBJECTIVE: The percutaneous treatment of pelvic abscesses has traditionally involved the placement of drainage catheters via a transgluteal, transrectal, or transvaginal route. These procedures are painful and prolonged. The goal of this study was to demonstrate the effectiveness of a one-step, single-puncture method for draining pelvic abscesses by use of a transrectal sonographically guided needle for aspiration and lavage instead of a two-step Seldinger technique for catheter placement. SUBJECTS AND METHODS: Thirty-three pelvic abscesses in 24 patients were drained by use of transrectal ultrasound guidance. All abscesses were initially seen on transrectal sonograms or CT scans and ranged from 2 to 11 cm in diameter. Abscesses were located in the prostate (n = five), seminal vesicles (n = five), pouch of Douglas (n = 21), and interloop (between bowel loops) (n = two). Causes of pouch of Douglas (cul-de-sac) abscesses included appendicitis (n = two), Crohn's disease (n = two), diverticulitis (n = three), trauma (n = six), HIV infection (n = two), complications of sigmoidectomy (n = one), complications of colectomy (n = one), pelvic inflammatory disease (n = two), and severe prostatitis (n = two). Interloop abscesses were attributable to HIV infection (n = one) and lymphoma (n = one). The procedure was performed without a cleansing enema or local anesthesia and required less than 30 min. An 18-gauge needle was inserted transrectally into the abscess cavity under transrectally guided sonography. The fluid collection was completely aspirated, and the cavity was lavaged with saline. Administration of antibiotics for 7-21 days, rather than prolonged catheter drainage, was used to treat residual infection. Resolution was documented after 7 days by sonography or CT examination. RESULTS: Transrectal aspiration was successful in treating 28 (85%) of the 33 pelvic abscesses in 21 (88%) of the 24 patients. Failure occurred in three patients, two with multiple abscesses and one with an enteric fistula for whom surgical drainage was subsequently required. The volume of aspirates ranged from 5 to 220 ml. There were no complications. CONCLUSION: Transrectal sonographically guided needle aspiration-lavage offers a one-step method for treating pelvic abscesses that does not require catheter placement or prolonged drainage. The procedure produces minimal discomfort and essentially no complications. Our results show that transrectal sonographically guided needle aspiration combined with antibiotic therapy is an effective treatment for pelvic abscesses. PMID- 7998541 TI - Treatment of autonomous thyroid nodules: value of percutaneous ethanol injection. AB - OBJECTIVE: Percutaneous injection of alcohol was recently proposed as an alternative to surgical and radioiodine treatments of autonomous thyroid nodules. The purpose of this study was to determine the value of this procedure and to define its limitations and indications when used for this purpose. MATERIALS AND METHODS: Thirty-one patients with autonomous thyroid nodules underwent a cycle of treatment with percutaneous injection of ethanol in multiple sessions (three to seven) on alternate days depending on the diffusion of the ethanol in the nodule. Fifteen patients were hyperthyroid, and 16 were euthyroid but had inhibited secretion of thyrotropin. The treatment results were evaluated by thyroid scintigraphy and sonography, by triiodothyronine, thyroxine, and thyrotropin assays, and by a thyrotropin-releasing hormone stimulation test 6 months after the end of treatment. Baseline scintigraphy demonstrated exclusive radionuclide uptake in the nodule in 29 patients and partial uptake in the extranodular tissue in two. The volume of the nodules ranged from 0.8 to 34.0 ml (mean +/- SD, 11.8 +/- 8.8 ml). Patients were monitored clinically for 24 hr after each session of ethanol injection to evaluate complications. Fifteen patients underwent a second cycle of ethanol injection when the results 6 months after the first cycle were unsatisfactory. The mean +/- SD follow-up was done at 26.9 +/- 12.3 months. RESULTS: Scintigraphy showed recovery of extranodular uptake of radionuclide in 72% of patients with nodules less than 13 ml in volume (maximum diameter [mean +/ SD], 2.7 +/- 0.7 cm; range, 1.4-4.0 cm) after one cycle of treatment and in 83% after two cycles. Among subjects with larger nodules, radionuclide uptake returned to normal in 9% after one cycle of treatment and in 9% after two cycles. For hyperthyroid patients, levels of thyroid hormones returned to normal in 69% after one cycle and in 77% after two cycles, and levels of thyrotropin returned to normal in 38% after one cycle and in 69% after two cycles; normal levels of thyrotropin were achieved in 93% of the euthyroid patients after one cycle of treatment and in 100% of these patients after two cycles. Symptoms resolved in 73% of the hyperthyroid subjects after the first cycle of treatment and in 93% of these subjects after the second. No important complications were observed; the most common side effects were acute pain at the injection site, referred pain, fever, transient dysphonia (< 12 hr), local hematoma, palpitations, and sinus tachycardia. CONCLUSION: Our results show that percutaneous injection of ethanol is appropriate therapy for autonomous thyroid nodules less than 13 ml in volume. The treatment should be considered successful when levels of thyroid hormones and thyrotropin return to normal. Nodule size appears to be the most important determinant of the success of the treatment. No complications that required termination of the treatment occurred. PMID- 7998542 TI - Percutaneous ethanol injection for the treatment of hepatic tumors: indications, mechanism of action, technique, and efficacy. AB - Percutaneous injection of ethanol for treatment of hepatic tumors was first described by Sugiura et al. [1] in 1983. To date, reported experience with the procedure has focused mainly on therapy of hepatocellular carcinoma (HCC) [2-15], with little information available regarding its use in treating metastatic liver lesions [16]. Interest in this technique has grown recently as a possible means of treating patients with metastatic liver disease. The purpose of this perspective is to review the indications, mechanism of action, technique, complications, and efficacy of percutaneous ethanol injection for liver tumor treatment. PMID- 7998543 TI - Percutaneous biopsy of the liver and kidney by using coaxial technique: adequacy of the specimen obtained with three different needles in vitro. AB - OBJECTIVE: The coaxial biopsy technique was evaluated with respect to the quality of specimens obtained from the liver and kidneys in vitro on sequential biopsies at the same site with each of three different biopsy needles. MATERIALS AND METHODS: For each of three different biopsy needles (aspiration 18-gauge Chiba, 18-gauge Sure-Cut, and 18-gauge Biopty), 30 sites (15 liver, 15 kidney) were selected for in vitro coaxial biopsy. At each site, an introducer was placed, through which three sequential biopsies were done. Blinded histopathologic analysis was used to grade the quality of specimens on a scale from 0 (no tissue) to 3 (best) for three criteria: adequacy of tissue for diagnosis, tissue fragmentation, and crush artifact. The overall score was the sum of the scores for the three individual criteria and ranged from 0 (no tissue) to 9 (best). RESULTS: Using an 18-gauge Chiba needle and coaxial technique, we found no significant reduction in specimen quality when we did multiple aspiration biopsies at the same site. However, no tissue was obtained (zero biopsy) from a large number of aspiration biopsies done with the Chiba needle, ranging from 24 of 30 for the first biopsy to 17 of 30 for the third biopsy. Specimen quality was reduced somewhat between the first and third biopsies when the 18-gauge Sure-Cut and Biopty needles were used. With the Sure-Cut needle, this reduction in quality was significant (p = .009) and was primarily related to increased tissue fragmentation and crushing. The reduction in quality with multiple biopsy attempts was less severe with the Biopty needle/gun. Although the mean score decreased from 6.6 for the first biopsy to 5.5 for the third biopsy, this reduction was not significant (p = .06). In addition, the Biopty gun, unlike the other two needles, had few zero biopsies. CONCLUSION: The use of a coaxial technique with an 18-gauge Biopty needle enables collection of a large amount of high-quality tissue for histopathologic analysis with a minimum number of failed biopsies as compared with the 18-gauge Chiba needle and the 18-gauge Sure-Cut needle. PMID- 7998544 TI - The gray-scale ink-jet printer: value in making hard copies of digital images. AB - Referring physicians often are supplied with copies of images to illustrate a report of the findings of a radiologic study or so that the radiologist can retain the original images. The increasing costs of production, film, and recovery of chemicals have enhanced the requirement for a clean, low-cost dry printing process. An ink-jet gray-scale paper printer (Unitone, Scitex Medical Systems, Bedford, MA) can print high-quality (300 dots per inch [dpi]) images with an effective 10-bit gray scale range by using the Hertz continuous ink-jet method [1-3], which does not require the use of a darkroom or hazardous chemicals. Several types of media (matte paper, glossy paper, transparency film) with a printing area of 26.9 x 43.7 cm (10.6 x 17.4 inches) may be used. The consumables are approximately 50-70% less expensive than the cost of silver halide film, providing a cost advantage over film for referral and archival copies. The results of an initial evaluation of the ink-jet printer at our institution are reported here. PMID- 7998545 TI - Digital image manipulation: what constitutes acceptable alteration of a radiologic image? PMID- 7998547 TI - New category of peer-review decision: rejection with opportunity to revise and resubmit. PMID- 7998546 TI - Sonography by the radiologist: self-referral, turf battles, and marketing. AB - Competition between radiologists and nonradiologists for the performance and billing of radiologic imaging examinations is, perhaps, most pervasive in the field of diagnostic sonography [1-3]. The purpose of this article is to help radiologists understand and deal with turf battles and the self-referral of clinicians and to describe marketing analyses and strategy that can be useful when attempting to decrease competition and increase referrals. PMID- 7998549 TI - The first clinical X-ray made in America--100 years. PMID- 7998548 TI - American martyrs to radiology. Clarence Madison Dally (1865-1904). 1936. PMID- 7998550 TI - History of the Department of Radiology at the University of Chicago. PMID- 7998551 TI - Absence of ureteral opacification below ureteral disruption: a sentinel CT finding. PMID- 7998552 TI - Mid-small-bowel obstruction. PMID- 7998553 TI - What are the relative accuracies of sonography and MR angiography? PMID- 7998554 TI - When to use an inferior vena cava filter. PMID- 7998555 TI - Diagnosis of deep-vein thrombosis of the legs. PMID- 7998556 TI - How does one determine when thrombolysis is sufficient? PMID- 7998557 TI - Arterioportal fistula after transjugular intrahepatic portosystemic shunt placement. PMID- 7998558 TI - Complications from enteroclysis tube insertion. PMID- 7998559 TI - Needle core biopsy of mammographic lesions. PMID- 7998561 TI - Gravity-assisted nonsurgical removal of a bronchial foreign body. PMID- 7998560 TI - Artifact caused by DX electrode. PMID- 7998562 TI - Laparoscopic sonography during laparoscopic cholecystectomy. PMID- 7998564 TI - Calculus in urethral pseudodiverticulum. PMID- 7998563 TI - Telling the patient her mammogram results. PMID- 7998565 TI - Needleless local anesthesia for tube changes. PMID- 7998566 TI - Clinical applications of renal scintigraphy. AB - Nuclear medicine techniques for evaluating the kidney and urinary tract have evolved from pioneering studies with primitive radiopharmaceuticals and hand-held probe detectors to a sophisticated technology capable of providing important physiologic and anatomic information. Advances in nuclear medicine and computer technology over the past decade have resulted in improved, clinically useful scintigraphic studies to assist clinicians in examining patients who have diseases of the genitourinary tract. However, renal scintigraphy is a complex subject. Five different radiopharmaceuticals are available for scanning the kidneys, multiple quantitative indexes can be generated, and protocols may vary depending on the clinical setting. The focus of this review is practical: to summarize the clinical advantages and disadvantages of the different radiopharmaceuticals; to review quantitative indexes that help interpret images; and to review the role of radionuclide scintigraphy in patients with suspected obstruction, pyelonephritis, and renovascular hypertension. PMID- 7998567 TI - Imaging of acute injuries of the cervical spine: value of plain radiography, CT, and MR imaging. AB - Imaging of injuries of the cervical spine has undergone substantial changes in the past 10 years. The use of CT and MR imaging has been emphasized by many authors. Other studies have stressed the proper use and interpretation of plain radiographs in the emergency setting. There is confusion about whether plain films, CT, or MR imaging is best used to evaluate specific injuries. This review explores the usefulness of CT and MR imaging in the diagnosis and management of acute injuries of the cervical spine and emphasizes the continued importance of conventional radiography. Specific examples that illustrate the relative merits of plain radiography, CT, and MR imaging are shown. PMID- 7998568 TI - Thoracic involvement in Behcet's disease: pathologic, clinical, and imaging features. AB - Behcet's disease is a rare form of vasculitis of obscure etiology. Any large or small artery, vein, or organ may be involved in an unpredictable combination. Intrathoracic manifestations of Behcet's disease consist mainly of thromboembolism of the superior vena cava and/or other mediastinal veins; aneurysms of the aorta and pulmonary arteries; pulmonary infarct and hemorrhage; pleural effusion; and, rarely, myocardial or pericardial involvement, cor pulmonale, and mediastinal or hilar lymphadenopathy. Chest radiography is the best diagnostic method for evaluating thoracic involvement in Behcet's disease. Because aneurysms may develop at the arterial puncture sites and veins may be quickly thrombosed after injection of contrast material, angiography and venography should be avoided whenever possible. Although no comparative studies are available, CT and MR angiography appear to be imaging techniques of choice for evaluating vascular involvement. Pulmonary parenchymal alterations depicted on CT scan have not been fully explored. PMID- 7998569 TI - Bronchogenic carcinoma in HIV-positive patients: findings on chest radiographs and CT scans. AB - OBJECTIVE: The radiographic manifestations of bronchogenic carcinoma in HIV positive individuals may resemble or accompany changes of inflammatory disease. To provide information that is useful in the differential diagnosis, we studied the findings on plain radiographs and chest CT scans in 30 HIV-positive patients with proven bronchogenic carcinoma and correlated the radiographic features with the presence or absence of thoracic opportunistic infection. SUBJECTS AND METHODS: Thirty HIV-positive individuals had bronchogenic carcinoma diagnosed at our institution between 1986 and 1993. Fourteen (47%) of the 30 had AIDS at the time of cancer diagnosis. All but one of the patients were men, and the median age at diagnosis was 48 years (range, 32-66 years). Most (90%) had a history of smoking. Eighteen (60%) of the 30 had a history of pulmonary tuberculosis, Pneumocystis carinii pneumonia, or both. We retrospectively reviewed all available chest radiographs (n = 27) and chest CT scans (n = 25) for tumor size and location, adenopathy, pleural disease, and pulmonary infiltrates. RESULTS: Eighteen tumors (60%) were peripheral, 11 (37%) were central (hilar or mediastinal), and one manifested as a metastatic pleural mass. Of the peripheral tumors, 17 (94%) were in the upper lobes. All the central tumors showed obstructive consolidation of lung in the distribution of the affected airway. Adenopathy was present in 63% of the patients, and pleural effusions or masses were seen in 33%. A history of tuberculosis or Pneumocystis carinii pneumonia was present in 83% of the patients with peripheral tumors but only 27% of the patients with central lesions (p = .005). Superimposed infiltrates were present in six patients (20%). Three (17%) of 18 peripheral tumors were obscured by or mistaken for inflammatory disease, delaying the diagnosis of cancer. CONCLUSION: Bronchogenic carcinoma usually manifests as a peripheral upper lobe mass in HIV positive patients with a history of tuberculosis or Pneumocystis carinii pneumonia, whereas central masses are more common in patients without a history of thoracic opportunistic infection. Carcinoma should be suspected in patients with peripheral lesions that persist despite appropriate antibiotic therapy. PMID- 7998571 TI - CT for asbestosis: value and limitations. AB - CT is more sensitive than clinical evaluation for the detection of asbestosis but is inevitably less sensitive and less specific than pathologic evaluation. For the asbestos-exposed individual, CT is useful for the evaluation of suspected lung masses, particularly rounded atelectasis [15], for identifying pleural plaques, and for confirming unequivocal asbestosis (grade 2 or grade 3 [8]). CT also will identify and quantify emphysema as a cause of physiologic impairment. Because clinicians commonly use CT to resolve clinical uncertainties, radiologists often feel pressured to categorize disease as unequivocally present or absent. Gamsu et al. [8] show that the borderline between normal and abnormal is not always sharply defined. In the absence of pathologic proof, the diagnosis of asbestosis must be based on a thoughtful evaluation of the likelihood of asbestosis by use of all available clinical, physiologic, and radiologic information. The scoring systems used by Gamsu et al. [8] offer a practical approach to defining the likelihood of asbestosis based on CT appearances. PMID- 7998570 TI - CT quantification of interstitial fibrosis in patients with asbestosis: a comparison of two methods. AB - OBJECTIVE: The likelihood of interstitial lung disease being detected on high resolution CT scans and having functional significance is often related to the severity of the disease. The extent and severity of the abnormalities seen on high-resolution CT are usually assessed subjectively. This study was undertaken to investigate whether a subjective semiquantitative scoring method or a method using a cumulation of the different high-resolution CT features of asbestosis were comparable in suggesting asbestosis in a group of patients with histopathologic confirmation of disease. A secondary objective was to compare the results of these two high-resolution CT methods with chest radiographs in the same population. MATERIALS AND METHODS: This study group consisted of 24 patients and six lungs obtained at autopsy. Histopathologic asbestosis was present in 25 of the 30 patients or lungs. The patients or lungs were imaged using selected high-resolution CT scans. The high-resolution CT scans were assessed in two ways. One used a subjective semiquantitative extent and severity score consisting of four levels of severity, while the other was a cumulative score adding the different types of high-resolution abnormalities in asbestosis. The commonest high-resolution CT abnormalities in the cases with confirmed asbestosis were interstitial lines (84%), parenchymal bands (76%), and architectural distortion of secondary pulmonary lobules (56%). Subpleural lines and honeycombing were less frequent. The histopathologic severity of asbestosis was independently graded on a four-point scale. Chest radiographs, when available, were classified according to the International Labor Organization (ILO) classification of pneumoconioses. RESULTS: With the subjective semiquantitative high-resolution CT severity score, asbestosis was suggested in 16 (64%) instances, all with disease. With the cumulative method, any one type of abnormality was present in 88% of cases with asbestosis, two types in 78%, and three in 56%. However, to include only cases with asbestosis, three different abnormalities had to be present. The high resolution CT scans were normal or near normal in five instances of asbestosis. Chest radiographs using the ILO classification predicted asbestosis with a lesser frequency than high-resolution CT in this selected population. CONCLUSION: We conclude that a subjective semiquantitative grading system of the extent and severity of asbestosis and a method using a cumulative addition of the different findings in asbestosis give similar results in suggesting the presence of disease. Thus, for the high-resolution CT detection of asbestosis, a combination of the cumulative number of different findings and an assessment of the extent and severity of the abnormalities could be complimentary. We also conclude that asbestosis can be present histopathologically with a normal or near normal high resolution CT scan. PMID- 7998572 TI - Calcification of aortic valve detected incidentally on CT scans: prevalence and clinical significance. AB - OBJECTIVE: Aortic valve calcification that is visualized on chest radiographs is considered a marker for clinically significant aortic stenosis, but the clinical importance of this finding on CT is unknown. Accordingly, we studied the prevalence and clinical relevance of aortic valve calcification found incidentally on CT scans of the chest. MATERIALS AND METHODS: After comparing computer records of chest CTs and echocardiograms, we identified 109 patients who underwent both studies during a 2-year period. Two thoracic radiologists reviewed the CT scans to identify and quantify aortic valve calcification. The quantity of aortic valve calcification was graded on a scale of 1 to 3, with grade 3 indicating the most severe calcification. The prevalence of calcification was correlated with patient age and sex. The findings on CT were correlated with hemodynamic data from echocardiography. At echocardiography, a peak aortic valve gradient of greater than 25 mm Hg was defined as abnormal. RESULTS: Aortic valve calcification was noted on CT scans in 33 (30%) of the 109 patients. Aortic valve calcification shown by CT was significantly more common in patients more than 65 years old (p < .01). Five (15%) of 33 patients with aortic valve calcification shown by CT had abnormal aortic valve gradients at echocardiography. In contrast, none of 76 patients without aortic valve calcification shown by CT had abnormal aortic valve gradients (p < .01). All five patients with abnormal aortic valve gradients had moderate quantities of aortic valve calcification seen on CT scans. Two of the five were younger than 55 years old. CONCLUSION: Aortic valve calcification is a common finding on CT scans and is usually clinically insignificant. Nevertheless, some patients with aortic valve calcification on CT have aortic stenosis, particularly those younger than 55 years old and those with moderately dense aortic valve calcification shown by CT. These patients may benefit from hemodynamic assessment of the aortic valve by echocardiography. PMID- 7998573 TI - Electron-beam CT demonstration of a right ventricular myxoma in an infant. PMID- 7998574 TI - Detecting residual tumor after excisional biopsy of impalpable breast carcinoma: efficacy of comparing preoperative mammograms with radiographs of the biopsy specimen. AB - OBJECTIVE: The purpose of this study was to ascertain whether a comparison of preoperative mammograms with radiographs of biopsy specimens is useful for determining the presence of residual breast tumor after an initial excision of impalpable breast cancer. MATERIALS AND METHODS: Radiographs of tissue specimens obtained at the initial biopsy of 125 impalpable breast cancers were compared with the preoperative mammograms to determine if the lesion seen on the mammogram was completely excised. All tumors were impalpable, necessitating preoperative wire localization. The biopsies were usually excisional, and no special efforts were made to remove additional surrounding tissue. Specimen radiographs were rated as showing no residual tumor if the lesion appeared to be completely excised, showing residual tumor if the lesion did not appear to be completely removed, or indeterminate for residual tumor if adequacy of excision was uncertain. The presence or absence of tumor at the margins of the surgical specimen was determined by histologic examination. These results were correlated with the presence or absence of residual breast cancer at subsequent mastectomy (n = 71) or reexcision (n = 54). RESULTS: The specimen radiograph showed complete excision of the mammographic lesion in 79 (63%) of the 125 cases. Tumor was found at mastectomy or reexcision in 35 of these cases, giving a false-negative rate for residual tumor of 44%. Incomplete excision was shown on 39 specimen radiographs. Eight of these 39 had no residual tumor, giving a false-positive rate of 21%. The sensitivity of the specimen radiograph for predicting the presence of residual tumor was 49%, specificity was 77%, and overall accuracy was 62%. The accuracy of pathologic examination of the margins of the biopsy specimen for predicting residual breast cancer was 58%. The specimen radiograph alone correctly identified 18 cases of residual tumor in which biopsy margins were indeterminate or negative for the presence of tumor. CONCLUSION: The specimen radiograph is not reliable enough to be used alone for determining the presence or absence of residual breast cancer after the initial excision of impalpable breast cancer. However, it can be of value in predicting the presence of residual tumor in those cases in which results of pathologic examination of biopsy specimen margins are either indeterminate or negative for the presence of tumor but the specimen radiograph shows incomplete excision of the mammographic lesion. PMID- 7998575 TI - Idiopathic localized dilatation of the ileum in adults: findings on barium studies. AB - OBJECTIVE: Idiopathic localized dilatation of the ileum is a rare entity characterized by a sharply demarcated segmental dilatation of the small bowel that is in line with the lumen. It is probably congenital in origin. Although more commonly diagnosed in children, it presents in adults as occult gastrointestinal (GI) bleeding or less often with abdominal pain. On pathologic examination, the mucosa may be ulcerated, but otherwise the wall is relatively normal. We analyzed the radiographic findings in nine previously unreported cases of this condition in adults. MATERIALS AND METHODS: Collaborative efforts resulted in the collection of nine cases from multiple institutions. In five cases, an enteroclysis had been performed; in three, a conventional small bowel series had been performed; and in one, the lesion was seen on a barium enema with reflux into the ileum. The mean age of patients was 52 years. In seven cases, pathologic correlation was available. In the other two patients, long-term clinical follow-up and repeat studies confirmed the diagnosis. Resected specimens showed a thin but otherwise normal wall with normal ganglion cells and nerve plexuses. Ulceration was noted in six of the seven resected cases. Two cases contained heterotopic gastric mucosa. GI bleeding and/or anemia was the most common (77%) presenting symptom. Abdominal pain and/or obstruction was present in slightly less than half the patients (44%). RESULTS: Lesions were 6-21 cm long and 4-13 cm wide, and all were located in the ileum. The dilated segments were bilobate in three cases, multilobate in three, spherical in two, and tubular in the other. The dilated area was always in line with the long axis of the bowel, not projecting to the side. No surrounding masses were seen. Except in three patients in whom ulcers were noted, the mucosa was normal. CONCLUSION: Idiopathic localized dilatation of the ileum should be suspected whenever a sharply demarcated area of lobulated small bowel dilatation is seen in a middle-aged patient with occult GI bleeding. The axial orientation distinguishes this condition from small bowel diverticula (including Meckel's). The lack of surrounding mass, mucosal irregularity, hypermotility, or fistulae help differentiate it from other causes of small bowel dilatation. PMID- 7998577 TI - Glycogenic acanthosis. PMID- 7998576 TI - Evacuation proctography in patients with solitary rectal ulcer syndrome: anatomic abnormalities and frequency of impaired emptying and prolapse. AB - OBJECTIVE: Solitary rectal ulcer syndrome is characterized by rectal bleeding, tenesmus, and difficult evacuation. Evacuation proctography can be used in patients with solitary rectal ulcer syndrome to diagnose associated internal or external rectal prolapse and delayed or incomplete rectal emptying. The objective of this study was to determine the proctographic abnormalities and the frequency of rectal prolapse and incomplete or delayed emptying in a large group of patients with solitary rectal ulcer syndrome. MATERIALS AND METHODS: Proctographic examinations of 53 patients with histologically proved solitary rectal ulcer syndrome were reviewed retrospectively. Evacuation proctography was done by a standard technique. The rate and completeness of rectal emptying and structural abnormality of the rectum were recorded. Comparison was made with a control group of 20 subjects who had no anorectal symptoms. RESULTS: Fourteen patients (26%) with solitary rectal ulcer syndrome had rectal irregularity at rest compared with none in the control group. Rectal prolapse developed on evacuation in 36 patients (68%) with solitary rectal ulcer syndrome: internal prolapse in 24 patients (45%), and external prolapse in 12 (23%). Descent of the pelvic floor on evacuation was greater in the solitary rectal ulcer syndrome group (median, 4.4 cm; range, 0-10.0 cm) than in the control group (median, 3.3 cm; range, 0.6-5.3 cm; p = .006). Thickened rectal folds were seen in 11 (55%) of 20 patients with solitary rectal ulcer syndrome examined with posteroanterior proctography. Evacuation was prolonged and incomplete in patients with solitary rectal ulcer syndrome (median, 15 sec; range, 3-60 sec) compared with control subjects (median, 10 sec; range, 3-30 sec; p = .012). All control subjects evacuated more than two thirds of the contrast material in less than 30 sec compared with only 41 patients with solitary rectal ulcer syndrome (77%). Overall, evacuation proctography disclosed delayed or incomplete emptying and/or rectal prolapse in 40 patients (75%) with solitary rectal ulcer syndrome compared with two control subjects who showed low-grade internal rectal prolapse only (p < .0001). CONCLUSION: Solitary rectal ulcer syndrome is significantly associated with prolonged and incomplete evacuation and with an increased prevalence of internal and external rectal prolapse. PMID- 7998578 TI - Hepatic artery thrombosis after liver transplantation: diagnosis with spiral CT. AB - OBJECTIVE: The purpose of this study was to prospectively evaluate spiral CT with maximum-intensity projection in the diagnosis of hepatic artery thrombosis in patients with liver transplants. SUBJECTS AND METHODS: Thirty liver transplant recipients (19 men, 11 women; mean age, 49 years) underwent Doppler sonography and spiral CT with maximum-intensity projection to evaluate both hepatic parenchyma and hepatic vessels. In five cases, these examinations were followed by angiography for suspected hepatic artery thrombosis. RESULTS: Among the 30 patients, results of both Doppler sonography and spiral CT were abnormal in five patients. In all five patients, Doppler sonography revealed an absence of intrahepatic arterial signal (sensitivity, 100%). Spiral CT showed the hepatic artery to be patent from its origin to the anastomosis and then occluded distally in four patients and showed occlusion of the entire hepatic artery in one patient (sensitivity, 100%). Aortography and/or selective arteriography of the celiac axis confirmed the diagnosis of hepatic artery thrombosis in all five cases. The other 25 patients had a normal clinical outcome, 24 with normal findings on Doppler sonograms (specificity, 96%), and 23 with normal findings on spiral CT. Two patients had false-positive CT studies because of technical failures (specificity, 92%). CONCLUSION: Spiral CT with maximum-intensity projection is highly accurate in identifying hepatic artery thrombosis after liver transplantation. PMID- 7998579 TI - Imidazoline Receptors: A Novel Approach to Hypertension--the Contribution of Rilmenidine. Symposium proceedings. Milan, Italy, June 8, 1993. PMID- 7998580 TI - Natriuretic effect of rilmenidine in anesthetized rats. AB - Rilmenidine binds to alpha 2-adrenoceptors and imidazoline receptors in the central nervous system and the kidney. To test the hypothesis that rilmenidine would increase sodium excretion, renal function was studied in rats with innervated and denervated kidneys to distinguish between indirect (via renal sympathetic nerves) and direct effects of rilmenidine on the kidney. Standard clearance techniques were used in Wistar rats anesthetized with thiobutabarbital to measure renal function during 80 minutes of infusion of 0.9% NaCl or rilmenidine (20 or 50 micrograms.kg-1.min-1 intravenously). Snares on abdominal arteries were used to offset hypotension induced by rilmenidine. Heart rate decreased by 80-120 beats/min with either dose of rilmenidine. At 20 micrograms.kg-1.min-1, rilmenidine increased total and fractional excretion of sodium and clearance of osmoles while decreasing free water clearance from innervated kidneys. There were no changes in these variables in chronically denervated kidneys. Direct recording of renal sympathetic nerve activity showed a progressive, marked decrease in nerve activity during the low-dose infusion of rilmenidine. At 50 micrograms.kg-1.min-1, rilmenidine produced a differential effect on the clearance of osmoles by innervated and denervated kidneys but both kidneys had an increase in free water clearance. The data indicate that rilmenidine increases sodium excretion indirectly in anesthetized rats by decreasing renal sympathetic nerve activity. At doses and infusion periods used in these studies, there was no evidence for a direct effect of rilmenidine on sodium excretion. The increase in free water clearance seen with the high dose of rilmenidine suggests that the inhibitory effect of alpha 2-adrenoceptor activation on vasopressin is involved at this dose.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7998582 TI - Role of imidazoline receptors in cardiovascular regulation. AB - The involvement of nonadrenergic imidazoline specific receptors in the central control of the vasomotor tone and in the mechanism of action of drugs bearing an imidazoline structure, or analogs, is now well documented. Imidazoline-specific binding sites were found in many tissues and species. Moreover, until now, it is only in the brainstem that such binding sites are associated with a function: the hypotensive effect of imidazoline-like drugs. Rilmenidine, which is an oxazoline structurally related to the reference imidazolines, exerts a central hypotensive effect of central origin involving imidazoline receptors. The selectivity of rilmenidine for the imidazoline receptors compared to alpha 2-adrenergic receptors could explain the low incidence of sedative side effects observed with this antihypertensive drug. A specific anti-imidazoline radioimmunoassay allowed us to detect the presence of an immunoreactive imidazoline-like substance in human sera. High levels of this immunoreactive substance are associated with high blood pressure in 20-30% of the hypertensive patients. This observation indicates that high levels of this immunoreactive substance in the serum can be associated with some kinds of primary hypertension. The cause-and-effect relation between these 2 phenomena has not yet been determined. This substance is in process of purification; it could be a candidate to be an endogenous ligand of the imidazoline receptors. PMID- 7998581 TI - Protection of focal ischemic infarction by rilmenidine in the animal: evidence that interactions with central imidazoline receptors may be neuroprotective. AB - Rilmenidine and idazoxan reduce the volume of focal ischemic infarctions produced by occlusion of the middle cerebral artery in the rat by 33% and 29%, respectively, by preserving neurons within the ischemic penumbra. In contrast, the alpha 2-selective antagonist SKF-86466 is without effect. The neuroprotective action of rilmenidine is dose dependent and parallels its antihypertensive actions. Neuroprotection cannot be attributed to changes in cerebral blood flow. We conclude that the neuroprotection produced by rilmenidine is attributable to an interaction with imidazoline receptors (IRs). However, the mechanism of action is not obvious. If it results from an action within the penumbra (direct), it is mediated by mitochondrial I-2 receptors on astrocytes, since cortical neurons are devoid of IRs. Neuroprotection might occur by selectively stimulating Ca2+ uptake into astrocytes, and thereby reducing Ca2+ uptake into neurons. Alternatively, rilmenidine may act indirectly to activate pathways in the brain that are neuroprotective. Neuroprotection may be a therapeutic target for rilmenidine and allied agents that act at central IRs. PMID- 7998583 TI - The high-risk hypertensive patient and the potential for brain imidazoline receptor binding by rilmenidine. AB - It is a fact that sympathetic outflow is a player in most, if not all, hypertensive conditions. A selective, effective, and relatively benign means of controlling it remains high on every clinician's wish list. In this supplement we examine the neurobiologic and pharmacologic evidence that the wish is nearing fulfillment. Recent evidence has documented the existence of nonadrenergic receptors in the brainstem, other than the well-known alpha 2-adrenergic receptors, that bind the imidazoline portion of vasoactive molecules. Pharmacologic science has wasted little time in developing compounds rich in imidazoline-like structures that, by supplanting norepinephrine (the natural cerebral neurotransmitter for sympathetic nervous system outflow) quiet sympathetic outflow, restrain heart rate and vasomotor influence, and reduce the negative quality-of-life effects induced by earlier centrally acting agents. This is because specific ligands for the imidazoline-preferring receptors appear to lower blood pressure without attendant drowsiness, dry mouth, and impaired mentation. Rilmenidine, the subject of this supplement, is the newest such agent, and the scientists involved in its development and clinical trials have produced heartening data. These developments presage good news in the clinic, and I am excited by their potential, particularly that for gaining deeper insight into human pressor phenomena. PMID- 7998584 TI - Effects of one-year treatment with rilmenidine on systemic hypertension-induced left ventricular hypertrophy in hypertensive patients. AB - In patients with essential hypertension, left ventricular hypertrophy (LVH) increases the risk for cardiovascular morbidity and mortality. Thus its reversal represents one of the principal end-points of antihypertensive treatment. We assessed the cardiovascular effects of 1-year antihypertensive treatment with rilmenidine (1 or 2 mg/day orally), a new oxazoline with a potent antihypertensive action that acts selectively through imidazoline-preferring receptors. In 11 hypertensive patients (mean age, 49 +/- 2 years) with LVH, we measured systemic hemodynamics, large artery compliance, cardiac anatomy, and endocrine function. Patients underwent M-mode and 2-dimensional echocardiography as well as Doppler and peripheral pulsed Doppler flowmetry, determination of plasma atrial natriuretic factor (ANF) levels and renin activity (PRA), and of 24 hour urinary electrolyte and creatinine excretion in control conditions (systolic/diastolic blood pressure, 148 +/- 3/102 +/- 1 mm Hg), 4 weeks after blood pressure normalization (131 +/- 2/84 +/- 2 mm Hg; p < 0.01), after 1 year of satisfactory antihypertensive treatment (142 +/- 3/90 +/- 1 mm Hg; p < 0.01) and, finally, 1 month after therapy withdrawal (155 +/- 3/106 +/- 2 mm Hg; difference not significant [NS]). One-year of rilmenidine treatment induced an improvement in brachial artery compliance (from 0.92 +/- 0.06 to 1.16 +/- 0.08 cm4/dyne; p < 0.05), which persisted after withdrawal of treatment (1.17 +/- 0.06 cm4/dyne; p < 0.05). LVH was reversed after 1 year of rilmenidine treatment (from 152 +/- 5 to 131 +/- 4 g/m2 body surface area; p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7998585 TI - Pharmacokinetics of rilmenidine in patients with chronic renal insufficiency and in hemodialysis patients. AB - The pharmacokinetics of rilmenidine (1 mg orally) was studied in 3 groups of patients with stable chronic renal insufficiency. This was an open, single-blind study following a single administration, and after 15 days of treatment. Group 1 included 11 patients with a creatinine clearance between 15 and 80 mL/min. Group 2 included 17 patients with a creatinine clearance < 15 mL/min. Group III included 10 hemodialysis patients. In patients with chronic renal failure, total plasma clearance and renal clearance of rilmenidine decreased; terminal half-life was 30-42 hours, which is clearly longer than previous values achieved in healthy volunteers. After repeated administration (1 mg daily in group 1, 1 mg every other day in group 2, 1 mg at the end of each dialysis session in group 3), the area under the curve was significantly increased, corresponding to drug accumulation. The steady state was reached after 6 days in patients in group 1 and after 8 days in patients in group 2. The pharmacokinetics of rilmenidine was linear since the terminal elimination half-life and renal clearance were not significantly different after single and repeated administration of rilmenidine. A positive correlation was found between rilmenidine total plasma clearance and creatinine clearance, and between rilmenidine renal clearance and creatinine clearance. Mean rilmenidine hemodialysance was 85 mL/min, that is, 26% of the rilmenidine renal clearance value achieved in healthy volunteers (330 mL/min). Thus, the following dosage schedule can be proposed. In patients whose creatinine clearance ranges between 15 and 80 mL/min, a 1 mg dose every day can be recommended.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7998586 TI - Efficacy and safety of rilmenidine in elderly patients--comparison with hydrochlorothiazide. The Belgian Multicentre Study Group. AB - The aim of this trial was to study the treatment of hypertension in the elderly, comparing a new oxazoline antihypertensive agent, rilmenidine, with the diuretic hydrochlorothiazide (HCZ). After 2 weeks on placebo, 88 elderly patients (mean age 75 years; 65 women), corresponding to strict inclusion criteria, were randomized to 8 weeks double-blind monotherapy with rilmenidine 1-2 mg/day (n = 46) or HCZ 25-50 mg/day (n = 42), with administration of potassium supplements as required. Particular emphasis was placed on the evaluation of safety: blood screens were repeated after 2, 4, and 8 weeks of treatment and symptoms were systematically evaluated every 2 weeks. The rilmenidine and HCZ groups were comparable at randomization, with baseline supine systolic/diastolic blood pressures of 167/101 mm Hg and 172/101 mm Hg, respectively. Both drugs induced a significant decrease in blood pressure: at 8 weeks, supine blood pressure had decreased to 154/89 mm Hg and to 155/87 mm Hg in the rilmenidine and HCZ groups, respectively (difference not significant between groups). Changes in heart rate did not differ significantly between groups (-3 bpm at 8 weeks). Drug-related symptoms were rare and the incidence was similar in both groups. Weight decreased significantly in the HCZ group by 1 kg (p < 0.001) and did not change in the rilmenidine group. After 8 weeks of monotherapy, expected variations in serum biochemistry were detected in the HCZ group, resulting in a significant difference in comparison with the rilmenidine group: serum potassium and chloride decreased significantly and uric acid levels increased significantly in the HCZ group.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7998587 TI - Long-term control of blood pressure by rilmenidine in high-risk populations. AB - Efficacy and acceptability of rilmenidine in populations with high cardiovascular risk has been established in short- or mid-term studies (1.5-6 months) enrolling relatively small numbers of patients. The present open study was undertaken to compare, on a larger scale, the efficacy and acceptability of a 12-month rilmenidine treatment in high-risk outpatients versus the results obtained in the general population and to check for unexpected adverse events. A total of 2,635 hypertensive patients (supine diastolic blood pressure [SDBP] > 90 mm Hg) were enrolled, including a high-risk population with 1,591 patients aged > 60 (60.3%), 1,007 patients with dyslipidemia (38.2%), 393 with diabetes (14.9%), 328 with chronic renal failure (12.4%), 301 with angina pectoris (11.4%), and 84 with chronic heart failure (3.2%). All patients were treated by rilmenidine 1 mg/day during the first 6 weeks; then (at 1.5 months), if SDBP was > 90 mm Hg, dosage of rilmenidine was 1 mg twice daily during the following 6 weeks. From month 3 to month 12, any other antihypertensive drugs could be added if SDBP remained > 90 mm Hg. In comparison with the general population, the percentage of high-risk patients whose monotherapy normalized blood pressure (SDBP < or = 90 mm Hg) was slightly lower at month 1.5 (58-66%, according to the risk group, vs 68% in the general population) and month 3 (73-82% vs 85%). At month 12, all treatments taken as a whole (monotherapy and combination therapy) led to the normalization of blood pressure in 94% of patients in the general population and in populations at risk.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7998588 TI - Involvement of imidazoline-preferring receptors in regulation of sympathetic tone. AB - We examined the contribution of imidazoline-preferring receptors (IPR) and alpha 2-adrenoceptors at different levels of the central nervous system in the antihypertensive and sympathoinhibitory actions of rilmenidine in 2 conscious animal models, the spontaneously hypertensive rat (SHR) and the normotensive rabbit. In conscious SHRs, we compared the potency of rilmenidine and clonidine administered intravenously into the lateral cerebral ventricle, the cisterna magna, and into the subarachnoidal space of the thoracolumbar spinal cord. In SHRs, we found that rilmenidine was more potent and more effective by the intrathecal than the intracisternal route. By contrast, clonidine was most effective after administration into the cisterna magna. Intravenous administration of rilmenidine or clonidine induced dose-dependent and prolonged decreases in blood pressure and heart rate. Neither rilmenidine nor clonidine altered mean arterial pressure or heart rate when given into the lateral cerebral ventricle. These data suggest that in SHRs the spinal cord may be an important site for the antihypertensive action of rilmenidine. We therefore characterized the receptor type involved. We observed in conscious SHRs that intrathecal post treatment with idazoxan, a mixed alpha 2-adrenoceptor and IPR antagonist, abolished the antihypertensive effect of rilmenidine, whereas 2-methoxyidazoxan, a selective alpha 2-adrenoceptor antagonist, caused only a partial reversal of the blood pressure effects of rilmenidine. These results suggest that rilmenidine acts mainly through IPR rather than alpha 2-adrenoceptors in the spinal cord. In view of these findings, we compared the hypotensive actions of rilmenidine and clonidine, administered into the lateral cerebral ventricle, the cisterna magna, and the subarachnoid space of the thoracolumbar spinal cord in conscious normotensive rabbits. Both drugs were less potent and effective when administered intrathecally than intracisternally. These experiments suggest that the hypotensive action of rilmenidine and clonidine in the rabbit is mediated through receptors mainly located in the brainstem. Further, we found that idazoxan reversed the hypotensive action of rilmenidine more readily than 2 methoxyidazoxan. Surprisingly, both idazoxan and 2-methoxyidazoxan completely reversed the depressor effects of clonidine. Therefore, in the rabbit, rilmenidine acts through IPR located in the brainstem and clonidine acts predominantly through alpha 2-adrenoceptors. In conclusion, our studies demonstrate that IPR are involved in the vasodepressor action of rilmenidine in both conscious SHRs and rabbits. However, although the main site of action of rilmenidine in SHRs may be located in the thoracolumbar spinal cord, in the rabbit it appears to be in the brainstem.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7998589 TI - Occupational risk factors for bladder cancer: results from a case-control study in Montreal, Quebec, Canada. AB - A population-based case-control study of the associations between various cancers and occupational exposures was carried out in Montreal, Quebec, Canada. Between 1979 and 1986, 484 persons with pathologically confirmed cases of bladder cancer and 1,879 controls with cancers at other sites were interviewed, as was a series of 533 population controls. The job histories of these subjects were evaluated by a team of chemist/hygienists for evidence of exposure to a list of 294 workplace chemicals, and information on relevant non-occupational confounders was obtained. On the basis of results of preliminary analyses and literature review, 19 occupations, 11 industries, and 23 substances were selected for in-depth multivariate analysis. Logistic regression analyses were carried out to estimate the odds ratio between each of these occupational circumstances and bladder cancer. There was weak evidence that the following substances may be risk factors for bladder cancer: natural gas combustion products, aromatic amines, cadmium compounds, photographic products, acrylic fibers, polyethylene, titanium dioxide, and chlorine. Among the substances evaluated which showed no evidence of an association were benzo(a)pyrene, leather dust, and formaldehyde. Several occupations and industries were associated with bladder cancer, including motor vehicle drivers and textile dyers. PMID- 7998590 TI - Menstrual cycle patterns and risk of breast cancer. AB - Menstrual cycle characteristics may reflect underlying endocrine patterns that influence the risk of breast cancer. Most previous studies of menstrual function and breast cancer risk have used retrospective reports of menstrual bleeding, which may be unreliable. To examine this association, the authors conducted a mail survey among 997 women who had recorded menstrual events prospectively over as many as 50 years, beginning in 1934. Compared with women with a median menstrual cycle length of 26-29 days, women who had cycles of extreme length at ages 25-29 years had a nearly twofold increased incidence of breast cancer (for a median cycle length of less than 26 days, adjusted relative risk (RR) = 1.9, 95% CI 0.9-4.1; for > or = 34 days, RR = 1.9, 95% CI 0.9-3.9). Statistical adjustment was made for age, family history of breast cancer, parity, age at menopause, age at first pregnancy, and Quetelet index (weight (kg)/height (m)2). Adjusting for age and other potential confounders and restricting the analysis to women who did not use hormones, women who experienced either a lesser (< 150) or a greater (> 350) cumulative number of cycles had an increased incidence of breast cancer (adjusted RR = 1.9, 95% CI 0.3-10.6, and RR = 1.8, 95% CI 0.5-6.0, respectively) compared with women who experienced 150-350 cycles. The findings are discussed in the context of current hormonal theories of breast cancer etiology. PMID- 7998591 TI - Defining the perimenopause for application in epidemiologic investigations. AB - The authors present a method for defining the inception of perimenopause that is based on self-reported data. The study sample (n = 1,550) was obtained from a 5 year longitudinal study of 2,569 Massachusetts women aged 45-55 years that began in 1981. The definition was derived from the ability of responses to questions concerning timing of the last menstrual period, menstrual regularity, and presence of menopausal symptoms (hot flashes/sweats) to predict menopause 3 years later. The two items that best defined the inception of perimenopause were 3-11 months of amenorrhea and increased menstrual irregularity for those without amenorrhea. This definition can easily be used in large epidemiologic investigations. PMID- 7998592 TI - Tracking and predictiveness of serum lipid and lipoprotein measurements in childhood: a 12-year follow-up. The Cardiovascular Risk in Young Finns study. AB - The authors analyzed tracking and predictiveness of serum lipid and lipoprotein measurements in Finnish children and young adults over a 12-year follow-up period. A representative sample of 3,596 healthy subjects aged 3-18 years was examined in 1980. The follow-up studies were done in 1983, 1986, 1989, and 1992. Data were available on serum lipids and lipoproteins, anthropometric measurements, dietary and smoking habits, and use of oral contraceptives. Complete data on serum lipids in 1980 and 1992 were available for 883 subjects (47% males), and they comprised the study cohort for this analysis. Significant tracking was found in each of the serum lipid variables studied. The range of 12 year correlations was 0.48-0.58, 0.53-0.58, 0.53-0.58, 0.57-0.59, and 0.33-0.37 for serum total cholesterol, low density lipoprotein (LDL) cholesterol, high density lipoprotein (HDL) cholesterol, the LDL:HDL cholesterol ratio, and triglycerides, respectively. Males showed more tracking than females; there was no clear age trend. Tracking of HDL2 cholesterol was better than that of HDL3 cholesterol (0.64 vs. 0.43, respectively; 3-year tracking). Apolipoproteins A-I and B showed similar amounts of tracking compared with HDL and LDL cholesterol, respectively. Approximately 50% of subjects who initially fell into the extreme quintiles of total cholesterol, LDL cholesterol, and HDL cholesterol were in the same quintiles after 12 years. In multiple regression analyses, childhood obesity, exercise, diet, and smoking habits did not markedly aid the prediction of adult serum lipid values. However, the use of two childhood measurements increased the amount of adult serum lipid variability explained. Although universal screening cannot be endorsed, these findings emphasize the importance of serum lipid measurements in the early detection of familial lipoprotein disorders and in the initial evaluation of coronary heart disease risk in childhood. PMID- 7998593 TI - Paralytic poliomyelitis in Romania, 1984-1992. Evidence for a high risk of vaccine-associated disease and reintroduction of wild-virus infection. AB - Although poliomyelitis due to wild-virus infection has virtually disappeared from Romania, with no cases having been documented between 1984 and 1989, vaccine associated paralytic poliomyelitis has been reported at very high rates for over two decades. In November 1990, to decrease the risk of vaccine-associated paralytic poliomyelitis, oral poliovirus vaccine produced in Romania was replaced by imported oral vaccine made by a Western European manufacturer. To better quantify the risk of vaccine-associated paralytic poliomyelitis and the impact of the change in vaccine manufacturer, the authors reviewed clinical, epidemiologic, and laboratory data on poliomyelitis cases that occurred in Romania from 1984 to 1992. Poliovirus isolates were characterized at the US Centers for Disease Control and Prevention. During the period 1984-1992, 132 confirmed cases of paralytic poliomyelitis were reported in Romania, of which 13 were classified as wild-virus-associated, 93 as vaccine-associated, and 26 as "of unknown origin." Wild type 1 poliovirus was isolated during 1990-1992 from nine of 13 (69%) cases in an outbreak that occurred primarily among undervaccinated gypsy children. Vaccine-associated cases were epidemiologically and virologically distinct from wild-virus cases. Of the 93 vaccine-associated cases, 45 children were recipients and 48 were contacts. The overall risk of vaccine-associated paralytic poliomyelitis in Romania (1 case per 183,000 doses of oral poliovirus vaccine distributed) was 14-fold higher than the risk in the United States. The risks of recipient vaccine-associated paralytic poliomyelitis related to the first dose of oral vaccine were similar for Romanian and imported vaccine (1 case per 95,000 doses and 1 case per 65,000 doses, respectively), as were the total risks of vaccine-associated paralytic poliomyelitis. These findings definitively demonstrate a substantially elevated risk of vaccine-associated paralytic poliomyelitis in Romania which was not affected by a change in oral poliovirus vaccine manufacturer. PMID- 7998594 TI - Sexually transmitted diseases, sexual behavior, and cocaine use in inner-city women. AB - The prevalence of untreated sexually transmitted diseases (STDs) was assessed in a cohort of 372 sexually active inner-city women (92% black, 49% US-born) with no history of injection drug use who were recruited in Brooklyn, New York, in 1990 and 1991. The presence of STDs was assessed via culture, serologic analyses, and medical history. Sexual and drug-use histories were obtained, as was a urine sample for toxicologic analysis. Thirty-five percent of the women had at least one STD (27% Trichomonas vaginalis, 6.8% Chlamydia trachomatis, 5.2% syphilis, 2.4% human immunodeficiency virus (HIV), and 1.4% Neisseria gonorrhoeae). US-born women were more likely than foreign-born (96% Caribbean) women to have an STD (50% vs. 22%; p < 0.001). Among US-born women, 61% of crack and/or cocaine users had an STD as opposed to 34% of non-users (OR = 2.9, 95% CI 1.6-5.5). Recent crack cocaine use was the strongest predictor of syphilis infection (OR = 12.8, p = 0.019), and was reported by each of the seven HIV-positive women. This study, based on a large sample with laboratory confirmation of both STDs and drug use, documents that women who use crack cocaine are at substantially higher risk of contracting an STD than other women. STD/HIV prevention programs in inner cities should target US-born women, particularly crack cocaine users. PMID- 7998595 TI - Snippets from the past: seventy years ago in the Journal. PMID- 7998596 TI - Re: "Increased mortality from brain tumors: a combined outcome of diagnostic technology and change of attitude toward the elderly". PMID- 7998598 TI - What happens to your manuscript: characteristics of papers published in volume 140. PMID- 7998597 TI - Re: "Risk of miscarriage and a common variant of the estrogen receptor gene". PMID- 7998599 TI - Human dento-gnathic metric variation in mesolithic/neolithic Ukraine: possible evidence of demic diffusion in the Dnieper Rapids region. AB - Dental and gnathic metrics from a series of Mesolithic and Neolithic cemetery samples in the Dnieper River valley (Ukraine) are compared. Both male and female Neolithic samples have larger dental dimensions, wider dental arcades, and a more robust mandibular corpus than do the Mesolithic samples. In addition, the relative variances (RVs) of bucco-lingual dental breadths (as measured by modified Levene's Tests) show an intriguing pattern of change from the Mesolithic into and through the Neolithic. Female RVs show a clear tenency to increase through time, while male RVs show more mixed tendencies. Such a pattern indicates that the increases in Ukrainian Neolithic dento-gnathic dimensions are plausibly attributable to low intensity gene flow (demic diffusion). Seen in the light of new chronometric, paleodietary, and paleolinguistic information, as well as in the context of recent archaeological models for agro-pastoralist origins in the North Pontic, these data suggest that gene flow via population interactions originating in or transient through the circum-Caucasus may have played an important role in producing the Ukrainian Neolithic dental increase. PMID- 7998600 TI - Maternal mortality or prolonged growth: age at death and pelvic size in three prehistoric Amerindian populations. AB - This study evaluates the relationship between age at death and pelvic size among adults in three prehistoric Amerindian populations. The issue is to identify if the pelvis continues to grow and remodel in adulthood, or if there is differential survivorship among adults, particularly among females, based on pelvic size. The samples used in this study are Indian Knoll, Pecos Pueblo, and Libben. Twenty-one measures of the pelvis are analyzed. A correlational analysis among individuals 18 years of age and older shows that the subpubic angle narrows with advancing age in both sexes. The suggested etiology is osteophytic growth on the ischiopubic ramus among older adults. A two-sample test comparing younger (ages 18-24) and older (25 years of age and older) adults shows that the linea terminalis (which represents the pubic and iliac components of the pelvic inlet) is significantly shorter in the younger age group, but this pattern is seen only in females. Two interpretations are consistent with this result. First, a female with a short linea terminalis (i.e., small pelvic inlet) may have died at a young age due to childbirth-related complications. In prehistory, maternal mortality may have been a leading cause of death, with pelvic inlet capacity being a determinant of survivorship among parturients. Second, the linea terminalis may be unique by continuing to grow in early adulthood in females but not in males; the growth occurs at the medial border of the pubis. Longitudinal growth studies of modern humans provide support for the second interpretation. The selective advantage of a later age at maturation of the pubis in females than males is that the period of growth is prolonged, thereby contributing to sexual dimorphism in pubic length and, correspondingly, linea terminalis length and pelvic inlet circumference. PMID- 7998601 TI - Multivariate analyses of elemental hair concentrations from a medieval Nubian population. AB - Elemental hair concentrations were obtained from 168 mummified individuals recovered during excavations of cementeries S and R (A.D. 550-1450), at Kulubnarti, Republic of the Sudan (Van Gerven et al., 1981). Concentrations of calcium (Ca), magnesium (Mg), strontium (Sr), manganese (Mn), zinc (Zn), iron (Fe), and copper (Cu) were determined using inductively coupled plasma emission spectrometry (ICP) (Sandford, 1984; Sandford et al., 1983). Following univariate statistical reanalyses of these data (Sandford and Kissling, 1993a, b), we applied principal component analysis and multidimensional scaling to clarify their multivariate structure. Similar underlying associations were revealed in the two cemeteries. The first principal component, consisting of Mg, Ca, Sr, and Mn, may reflect inherent chemical similarities coupled with specific dietary factors (e.g., vegetation intakes) and physiological processes (e.g., bone remodeling). The second principal component, a contrast between Fe and Zn, may be due to their competitive relationship during absorption. The third principal component consists of Cu alone (in cemetery S), and Cu and Fe (in cemetery R), suggesting utilization of animal protein and an underlying synergism between Cu and Fe, respectively. Multidimensional scaling substantiates a three-dimensional model for describing elemental covariation. While interpretation of the first two dimensions was analogous to those of the first two principal components, the third dimension may represent antagonism between pairs of elements during absorption, transport and/or utilization (cemetery R: Cu vs. Zn; cemetery S: Cu vs. Zn, Fe vs. Mn). While these results provide the most persuasive evidence to date that elemental hair concentrations from this population reflect chiefly biogenic processes, isolation of diagenetic and exogenous effects requires further investigation through controlled studies. PMID- 7998602 TI - Mandibular growth and function in Archaeolemur. AB - Ontogenetic changes in the morphology of the mandibular symphysis are described in Archaeolemur so as to infer the functional significance of symphyseal fusion in this subfossil Malagasy lemur. The first regions of the symphysis to show a more complex morphology were the lower and anterior borders of the joint and, to a lesser extent, the lingual borders of the superior and inferior transverse tori. During growth, these regions became increasingly rugose and encroached upon a centrally located, smooth, "oval" region, which may have been a principal pathway for neurovascular structures communicating with the unfused joint. In subadults, the symphysis was completely fused except for the lingual surface of the inferior transverse torus, where a patent suture and potential space were present between dentaries. Thus, in Archaeolemur there was an age- and size related pattern of increased symphyseal ossification or fusion that was complete by adulthood. The morphology of the interlocking bony processes and the sequence of ossification in the symphysis suggest that increased dorsoventral shear stress during mastication was the most likely determinant of symphyseal fusion in Archaeolemur. The allometric pattern of greater symphyseal fusion may be linked to the presence of relatively greater dorsoventral shear in adults due to an increased recruitment of balancing-side jaw-muscle force. There is little indication that the symphysis of juvenile Archaeolemur was buttressed to resist forces associated with "wishboning" during mastication or vertical bending during incision. Our observations, as well as those of others, suggest that symphyseal fusion in primates occurs initially as a response to increased dorsoventral shear during mastication. Therefore, wishboning stress might only become a major determinant of symphyseal form and function in those taxa that develop a fused symphysis to counter increased dorsoventral shear. PMID- 7998603 TI - Intra- and interobserver concordance in scoring Harris lines: a test on bone sections and radiographs. AB - Little attention has been devoted to assessing the reproducibility of (paleo) pathological observations. Harris lines (HL) are among the markers most used to determine chronology of stresses suffered during growth. Nevertheless, their scoring entails remarkable methodological difficulty. Bone sections (S) and radiographs (R) of 29 adult tibiae of archeological provenance (medieval) were scored for HL by five observers. At regular intervals of time, each observer gave two independent counts on both series. Results show a) a substantial interobserver disagreement of HL estimates for both sectional and radiographic records, and b) a high level of intraobserver error. PMID- 7998604 TI - Thin enamel and other tooth components in Neanderthals and other hominids. PMID- 7998606 TI - The anatomy of physiology's body of knowledge. PMID- 7998605 TI - Human cranial variability past and present. PMID- 7998607 TI - Attendance and grades in a human physiology course. AB - Teaching a lecture course in introductory human physiology with 40-183 students provided an opportunity to test the hypothesis that regular attendance is correlated with higher examination scores. Data on 556 students were recorded during five semesters, each consisting of three classes per week for 14 weeks. The students were in the second year of pharmacy, nursing, physical education, and dental hygiene programs. Attendance was recorded in each class. Regular attendance was encouraged but was not used to influence scores. The maximum possible score was 400 points, based on two 1-h examinations and a 2-h final examination. Examinations consisted of multiple-choice questions derived from reading assignments in a required textbook. Linear regression analysis indicated a small negative relation between total point scores and absences, amounting to an average decrease of 2 points for each absence, or a decrease of 0.5% per absence. Correlation coefficients averaged -0.33. The results suggest that regular attendance was helpful in a statistical sense but was not a decisive factor in learning human physiology as presented in current textbooks. PMID- 7998608 TI - Basic science curriculum during residency: justification based on in-training examination scores. AB - The American Board of Surgery is increasing its emphasis on competency in surgical basic science as part of residency training. The 1991 American Board of Surgery In-Training Examination (ABSITE) contained 135 questions designated as basic science to assess residents' knowledge. We reviewed the separate progression of scores in clinical and basic sciences at Wayne State University (WSU) surgical residency and nationally through the 1991 ABSITE report. Regression analysis of WSU data yielded a slope (% correct answers per postgraduate year) of 5.3 for clinical and 2.4 for basic science scores (P < 0.001 by t-statistic applied to regression slopes). These data imply a progression of knowledge during residency but at a significantly slower rate for basic science. The national data confirm this trend, although we were unable to evaluate it statistically. This situation illustrates the need for organized teaching of clinically relevant basic science as part of a residency curriculum. PMID- 7998609 TI - Certainty and uncertainty in science: the subjectivistic concept of probability in physiology and medicine. AB - Most physiological scientists have restricted understanding of probability as relative frequency in a large collection (for example, of atoms). Most appropriate for the relatively circumscribed problems of the physical sciences, this understanding of probability as a physical property has conveyed the widespread impression that the "proper" statistical "method" can eliminate uncertainty by determining the "correct" frequency or frequency distribution. However, many relatively recent developments in the theory of probability and decision making deny such exalted statistical ability. Proponents of Bayes's subjectivist theory, for example, assert that probability is "degree of belief," a more tentative idea than relative frequency or physical probability, even though degree of belief assessment may utilize frequency information. In the subjectivist view, probability and statistics are means of expressing a consistent opinion (a probability) to handle uncertainty but never means to eliminate it. In the physiological sciences the contrast between the two views is critical, because problems dealt with are generally more complex than those of physics, requiring judgments and decisions. We illustrate this in testing the efficacy of penicillin by showing how the physical probability method of "hypothesis testing" may contribute to the erroneous idea that science consists of "verified truths" or "conclusive evidence" and how this impression is avoided in subjectivist probability analysis. PMID- 7998610 TI - The word is the deed: the ideology of the research paper in experimental science. AB - The research publication epitomizes the practice of contemporary science. This article emphasizes the underlying ideological basis and comments on the educational implications, particularly for graduate students. An attitudinal shift in the acquisitions of knowledge led to Henry Oldenburg's "invention" of the research article in the 17th century. Science was seen to be an open, cooperative activity, incremental in nature, with contributors building on previous work and submitting their work to scrutiny. Brief papers replaced weighty tomes. Subtle changes over the next century led to the current format. Ethnographic and textual analyses have shown that scientific facts are not revealed but constructed and that the research paper is carefully crafted to serve its twin functions, to inform and to persuade. Manufactured knowledge must be communicated and certified to preserve the communal nature of the investigative enterprise. Publication in a recognized forum fulfills that need. The word IS the deed. PMID- 7998611 TI - An educational tool for understanding the cardiopulmonary changes associated with aging. AB - Normal aging is associated with cardiac, vascular, and pulmonary adaptations that significantly affect the individual's ability to maintain homeostasis. To understand the changes associated with aging, we developed a laboratory exercise that compares and contrasts the cardiopulmonary responses to exercise in a young and an older individual. We also developed this interactive tool because it is our experience that learning is better facilitated when students are encouraged, and required, to become an active and integral part of the educational process. This exercise provides a unique opportunity to analyze, integrate, and interpret the changes associated with aging because more is learned about how a system operates when it is forced to perform than when it is idle. In this laboratory exercise, basic anatomical and physiological data about aging are provided. Subsequently, figures are presented that illustrate the responses of specific cardiopulmonary variables during exercise (e.g., heart rate, cardiac output, blood pressure), and the students are challenged to analyze and assimilate information from the figures, answer questions, make calculations, and plot graphs. The laboratory does not require equipment or software, only rules and pencils. Questions, and answers to them, are provided in the appendix. The emphasis is on the application of basic science principles, interpretation of pictorial or tabular material, and problem solving skills. In addition, an evaluation instrument was developed to assess the effectiveness of this instructional tool in an academic setting. Specifically, the evaluation instrument addressed four major components, including aims and objectives, content of materials, components and organization, and summary and recommendations. PMID- 7998612 TI - The Claude Bernard Distinguished Lecture. The excitement and challenge of teaching physiology: shaping ourselves and the future. PMID- 7998613 TI - An educational tool for understanding the cardiopulmonary changes associated with heart failure. AB - We wanted a new and innovative method of engaging students in interactive learning. To this end, we developed an educational tool that compares and contracts the cardiopulmonary responses to exercise in an individual with heart failure with an individual with normal cardiac function. This exercise provides a unique opportunity to analyze, integrate, and interpret the changes associated with heart failure because more is learned about how a system operates when it is forced to perform than when it is idle. In this laboratory, basic anatomical and physiological data about heart failure are provided. Subsequently, figures are presented that illustrate the response of specific cardiopulmonary variables during exercise (e.g., heart rate, cardiac output, blood pressure), and the students are challenged to analyze and assimilate information from figures, answer questions, make calculations, and plot graphs. The answers to the questions are provided. The students reported that this tool was an interesting and thoughtful approach to learning cardiopulmonary physiology. We conclude that this method is pedagogically sound inasmuch as students are forced to draw conclusions with directed exercises and questions. PMID- 7998614 TI - Psychophysical determination of visual processing time by comparing depth seen in Pulfrich and Mach-Dvorak illusions. AB - A practical course for preclinical medical students was developed to illustrate aspects of binocular vision and mechanisms of primary visual transduction. It is based on a graphic analysis of two optical illusions, the Pulfrich and the Mach Dvorak phenomena. A pendulum swinging in a plane perpendicular to the direction of observation appears to follow an elliptical path when viewed binocularly with a filter in front of one eye (Pulfrich illusion) or with alternating occlusion of the right and left eye above a critical frequency (Mach-Dvorak illusion). The Pulfrich phenomenon permits us to determine the relationship between perceived illusory depth and filter density. Analyzing the Mach-Dvorak phenomenon allows us to determine the dependence of illusory depth on interocular delay. Comparison of both determinations (depth against transmission and depth against time) permits us to establish, without complex calculations, the effect of luminescence on visual processing time. In addition, this course illustrates a general methodological concept mentioned by Popper: students make an unexpected observation, put forward a testable hypothesis, and try to falsify it. PMID- 7998615 TI - Hydraulic analogs as teaching tools for bioelectric potentials. AB - Hydraulic analogs of bioelectrical potentials are proposed as teaching tools in helping students with no formal background in physics and mathematics. Membrane capacitance is simulated by a water reservoir, V, whose variable level is the membrane potential. Resting membrane potential is simulated by a large capacitance reservoir of fixed level, connected to reservoir V through a tube having the role of the electrical conductance of the membrane. Injection of electrical current into the cell is simulated by injection of water into the membrane capacitance reservoir. Reversal potentials of the end-plate potential are simulated by another water reservoir, with fixed level (analogous to the reversal potential of the end-plate potential) connected to the membrane capacitance reservoir through a tube corresponding to the acetylcholine-activated ion channels. Different phases of the synaptic potential are then described using the hydraulic analogs. Hydraulic analogs have proved, in our experience, to be an efficient tool in complementing the already established electrical equivalents. PMID- 7998616 TI - A hydrostatic model of membrane potential. AB - A model based on the elementary principles of hydrostatic and air pressures is proposed for classroom demonstration of some concepts related to membrane potential. The instrument comprises a system of U tubes, pressure gauges, stopcocks, and syringes. Intracellular and extracellular ionic concentrations are represented in the model by the pressure heads of fluid columns in the twin limbs of the U tubes. Membrane channels are simulated by stopcocks interposed at the bends of the U tubes. The Na(+)-K+ pump is represented by the syringes that shunt fluid from one limb of the U tube to the other. The pressure of air trapped above the fluid columns is equivalent to electrical potential. PMID- 7998617 TI - Effectiveness of an active method in teaching physiology. AB - A three-year study was conducted in search of a better method of teaching physiology that would enhance the critical thinking skills of first-year nursing students in Istanbul University, Florence Nightingale College of Nursing. Three different methods of teaching were used: 1) a straight lecture method, 2) an active method with no previous preparation of students, 3) an active method with previous preparation. Each method was evaluated by end-of-term marks, student feedback in that year, and a follow-up the next year by questionnaires distributed to both students and nursing teachers. The results of end-of-term examinations and Student Acceptance Indexes, as well as comments of nursing teachers, show that the active method of teaching is better than straight lecture and that the active method is most effective when students are familiarized with it beforehand. PMID- 7998618 TI - Evaluation of a summer enrichment physiology course for matriculating medical students. AB - A summer enrichment physiology course for matriculating medical students has met a number of short-term goals, including bringing the students to the level of average medical student performance by the end of the summer. The long-term benefit of the program was evaluated by constructing a prospective expectation for each member of the medical class. Physiology grades obtained by past medical students were regressed on their undergraduate grades and MCAT scores. This regression model was used in a prospective manner to predict a physiology course grade for the entering class. Six of the seven summer program participants achieved scores equal to or higher than their predicted scores. Additionally, the regression model identified prospectively four of the six medical students who scored below 70% for the medical physiology course. This study suggests that a summer enrichment program can benefit participants. PMID- 7998619 TI - Comparison of a computer simulation program and a traditional laboratory practical class for teaching the principles of intestinal absorption. AB - Here we describe an evaluation of the effectiveness, compared with a traditional laboratory, of an interactive computer-assisted learning (CAL) program, which simulates a series of experiments performed using isolated, everted sacs of rat small intestine. The program is aimed at undergraduate students of physiology and is designed to offer an alternative student-centered learning approach to the traditional laboratory-based practical class. The evaluative study compared two groups of second-year undergraduate students studying a module on epithelial transport: one group worked independently using the CAL program and associated learning materials, and the other group followed a conventional practical class approach, working in the laboratory under supervision. Knowledge gain of each group was measured by means of a test consisting of a range of question types (e.g., short-answer factual, calculation, interpretation) given to students before and after the module. Student attitude to both approaches was assessed by questionnaire, and the resource requirements were also compared. It was found that the knowledge gain of both groups of students was the same, that students had a positive attitude toward using CAL programs of this type, and that the cost of the conventional laboratory-based approach was five times greater. The potential for integrating CAL programs into the undergraduate curriculum is discussed. PMID- 7998620 TI - Homelessness in America. PMID- 7998621 TI - What was new at Yokohama--women's voices at the 1994 international HIV/AIDS conference. PMID- 7998622 TI - Annotation: what will be the role of HIV infection reporting? PMID- 7998623 TI - The evaluation of needle exchange programs. PMID- 7998624 TI - Challenges to the control of sexually transmitted diseases in Africa. PMID- 7998625 TI - Sexually transmitted diseases: a neglected public health priority. AB - Sexually transmitted diseases remain uncontrolled although millions of cases occur annually in the United States. The advent of acquired immunodeficiency syndrome (AIDS), which is also a sexually transmitted disease, has not altered this situation. The major portion of federal funding for sexually transmitted diseases is allocated to a search for an AIDS vaccine or cure. State health department funding for sexually transmitted diseases, although only a small fraction of the $1.3 billion AIDS research budget of the National Institutes of Health, is largely consumed by AIDS. A single adequately funded sexually transmitted disease control program that applies well-established public health principles for the control of communicable diseases would make sense. However, a consensus to develop and support such a program does not exist in the United States. PMID- 7998626 TI - Standardized protocols for condom breakage and slippage trials: a proposal. AB - In the absence of well-controlled studies on the clinical effectiveness of condoms against pregnancy and sexually transmitted diseases, breakage and slippage data may provide the best indication of the protection offered by condom use. According to the recent literature, condom breakage rates range from 0% to 12%, with many US studies falling in the 2% to 5% range. Few studies have collected slippage data. In addition to discussing methodological issues associated with these studies, we propose a standardized protocol for future condom breakage and slippage trials and discuss how results may be used to estimate perfect-use and typical-use pregnancy rates. PMID- 7998627 TI - Condom availability in schools: the need for improved program evaluations. AB - OBJECTIVES: This article examines the impact of contentious local debates on the design and implementation of school-based condom availability programs. METHODS: Information about condom availability in schools was reviewed by 50 leading educators and health officials at a 1992 forum held in Menlo Park, Calif. RESULTS: Few existing condom availability programs were designed to yield definitive data on sexual risk-taking behavior or other measures of program effectiveness. CONCLUSIONS: In the debate over school-based condom availability programs, as in many aspects of human immunodeficiency virus (HIV) prevention programs, scientific, moral, and political concerns overlap. Behavioral research into the potential effectiveness of such programs can help inform debates about fundamental values concerning sexual decision making and privacy, family integrity and parental autonomy, and public health. PMID- 7998628 TI - Lifetime and five-year prevalence of homelessness in the United States. AB - OBJECTIVE: Intense debate exists concerning the number of homeless people in the United States. Previous studies, counting currently homeless people, have provided point-prevalence estimates of homelessness but have been criticized on methodological grounds. This study reports lifetime and 5-year prevalence estimates of homelessness using a different methodological approach. METHODS: Random-digit dialing was used to interview 1507 adults living in households with telephones in the 48 contiguous states in the fall of 1990. Respondents were asked whether they had ever been homeless and if so, where they had slept while homeless. RESULTS: Lifetime and 5-year prevalence of all types of homelessness combined were 14.0% (26 million people) and 4.6% (8.5 million people), respectively. Lifetime "literal homelessness" (sleeping in shelters, abandoned buildings, bus and train stations, etc.) was 7.4% (13.5 million people). Five year (1985 through 1990) prevalence of self-reported homelessness among those who had ever been literally homeless was 3.1% (5.7 million people). CONCLUSIONS: The magnitude of the problem of homelessness is much greater than most previous attempts to enumerate homeless people have led us to believe. This finding requires reconsideration of inferences about the causes of homelessness that were derived from point-prevalence studies of currently homeless people. PMID- 7998629 TI - The effect of moderate alcohol use on the relationship between stress and depression. AB - OBJECTIVES: The purpose of the study was to determine whether moderate alcohol use mediates or buffers the effect of stress on depression in a group of non Hispanic White men and women. METHODS: Data are from the Los Angeles Epidemiological Catchment Area cohort. Individuals were assessed at two time periods, 1 year apart. Mean depression scores were analyzed for each level of stress and alcohol use. RESULTS: In the simultaneous presence of both chronic strain and negative life events, a U-shaped pattern was observed in which abstainers and light and heavy drinkers had higher depression scores at the second time period than did light-moderate and moderate alcohol users. The U shaped relationship remained when the effects of sex, age, and physical health status were controlled. CONCLUSIONS: Light-moderate and moderate drinkers had less depression in the presence of stress than persons in other more extreme drinking categories. Moderate alcohol use may serve as a proxy for a spectrum of generally moderate behaviors that either attenuate the effect of stress on depression or suppress the effects of stress. PMID- 7998630 TI - The effects of HIV/AIDS intervention groups for high-risk women in urban clinics. AB - OBJECTIVE: This study reports the results of a behavior change intervention offered to women at high risk for human immunodeficiency virus (HIV) infection seen in an urban primary health care clinic. METHODS: Participants were 197 women randomly assigned to either an HIV/acquired immunodeficiency syndrome (AIDS) risk reduction group or a comparison group. Women in the HIV/AIDS intervention group attended five group sessions focusing on risk education; skills training in condom use, sexual assertiveness, problem solving, and risk trigger self management; and peer support for change efforts. Women in the comparison group attended sessions on health topics unrelated to AIDS. RESULTS: At the 3-month follow-up, women in the HIV/AIDS intervention group had increased in sexual communication and negotiation skills. Unprotected sexual intercourse had declined significantly and condom use had increased from 26% to 56% of all intercourse occasions. Women in the comparison group showed no change. CONCLUSIONS: Socially disadvantaged women can be assisted in reducing their risk of contracting HIV infection. Risk reduction behavior change interventions should be offered routinely in primary health care clinics serving low-income and high-risk patients. PMID- 7998631 TI - A national surveillance system for newly acquired HIV infection in Australia. National HIV Surveillance Committee. AB - OBJECTIVES: The purpose of this study was to describe the establishment of a national surveillance system for newly acquired human immunodeficiency virus (HIV) infection and present the first 3 years' results. METHODS: All new cases of diagnosed HIV infection were reported to the national HIV surveillance center through state and territory health authorities. Information sought on each case included evidence of whether the infection had been newly acquired, defined by the diagnosis of HIV seroconversion illness or by the report of a negative or indeterminate HIV antibody test result occurring within the 12 months prior to diagnosis of infection. RESULTS: Of 3602 reported cases of HIV infection in adults and adolescents newly diagnosed in Australia between 1991 and 1993, 11.4% were identified as newly acquired. The majority (85%) of cases of newly diagnosed HIV infection occurred among men who reported homosexual contact, and 15% of these cases were identified as newly acquired. Average age at diagnosis was 31 years for cases of newly acquired infection and 34 years for other cases. CONCLUSIONS: Surveillance for newly acquired HIV infection has been established at a national level in Australia and provides valuable information for planning primary HIV prevention programs. PMID- 7998632 TI - Mandatory anonymous HIV surveillance in Denmark: the first results of a new system. AB - OBJECTIVES: This paper describes the principles and first results of the newly implemented anonymous mandatory human immunodeficiency virus (HIV) reporting system in Denmark. METHODS: The system is based on a serially numbered form that is circulated among the laboratories, the physicians, and the national surveillance unit. All laboratories doing confirmatory tests for HIV antibodies must send a report form along with any positive test results. Before forwarding the form, the laboratory is to fill in the top part with the name and address of the requesting physician and send the back copy to the surveillance unit. The physicians are mandated by law to fill in the form with data on the patient and to keep two copies for their own files before sending the original to the surveillance unit. RESULTS: After a revision of the system, a response rate of 95% was obtained. CONCLUSIONS: We have established an anonymous mandatory HIV surveillance system in Denmark that enables routine evaluation of the completeness of reporting and nonresponding physicians to be reminded of their duty to report. Also, the physicians can act as mediators between patients and researchers; therefore, nested studies can be done without breaking the anonymity of the patient. PMID- 7998633 TI - HIV infection in homosexual and bisexual men 18 to 29 years of age: the San Francisco Young Men's Health Study. AB - OBJECTIVES: Recent studies suggest very high human immunodeficiency virus (HIV) infection rates in some populations of younger homosexual men, but these studies may represent only particularly high-risk populations. The current study obtained population-based data on the HIV epidemic in young homosexual/bisexual men. METHODS: A household survey of unmarried men 18 through 29 years of age involved a multistage probability sample of addresses in San Francisco. A follow-up interview and HIV test for men who were HIV negative at baseline were completed; the median follow-up was 8.9 months. RESULTS: Sixty-eight of 380 homosexual/bisexual men (17.9%) tested HIV seropositive. Sixty-three percent of men reported one or more receptive anal intercourse partners in the previous 12 months, and 41% of those men did not use condoms consistently. The HIV seroincidence rate among those seronegative at first study was 2.6% per year. CONCLUSIONS: HIV infection rates in young homosexual men in San Francisco are lower than those in the early 1980s; however, the rate of infection in these men, most of whom became sexually active after awareness of AIDS had become widespread, threatens to continue the epidemic in the younger generation at a level not far below that of a decade ago. PMID- 7998634 TI - Factors mediating changes in sexual HIV risk behaviors among gay and bisexual male adolescents. AB - OBJECTIVES: Factors mediating changes in sexual behaviors that increase the risk of human immunodeficiency virus (HIV) infection were monitored in a group of gay and bisexual male adolescents. METHODS: One hundred thirty-six males aged 14 to 19 years (Hispanic, 51%; African-American, 31%) were recruited from one gay identified agency, were assessed at four points over a 1-year period, and participated in HIV preventive intervention sessions. RESULTS: Significant reductions occurred in the number of unprotected same-sex anal and oral acts. Those with less risk in their previous sexual history, those who did not engage in commercial sex, and those who attended more HIV intervention sessions were more likely to reduce their sexual risk. The impact of sessions varied significantly by race/ethnicity: African-American youths reduced their risk acts most dramatically. Abstinence was consistently and significantly more likely among younger youths and those who had been abstinent before enrollment. The youths significantly reduced the number of sexual partners following the intervention; this reduction in partners was maintained through the 12-month follow-up and was greatest among youths with no involvement in commercial sexual activity (prostitution). CONCLUSIONS: The efficacy of HIV prevention programs must be empirically evaluated. PMID- 7998635 TI - Health care-seeking behavior related to the transmission of sexually transmitted diseases in Kenya. AB - OBJECTIVES: The purpose of this study was to identify health-care seeking and related behaviors relevant to controlling sexually transmitted diseases in Kenya. METHODS: A total of 380 patients with sexually transmitted diseases (n = 189 men and 191 women) at eight public clinics were questioned about their health-care seeking and sexual behaviors. RESULTS: Women waited longer than men to attend study clinics and were more likely to continue to have sex while symptomatic. A large proportion of patients had sought treatment previously in both the public and private sectors without relief of symptoms, resulting in delays in presenting to study clinics. For women, being married and giving a recent history of selling sex were both independently associated with continuing to have sex while symptomatic. CONCLUSIONS: Reducing the transmission of sexually transmitted diseases in Kenya will require improved access, particularly for women, to effective health services, preferably at the point of first contact with the health system. It is also critical to encourage people to reduce sexual activity while symptomatic, seek treatment promptly, and increase condom use. PMID- 7998636 TI - Does the promotion and distribution of condoms increase teen sexual activity? Evidence from an HIV prevention program for Latino youth. AB - OBJECTIVES: Opponents of condom availability programs argue that the promotion and distribution of condoms increases adolescent sexual activity. This assertion was tested empirically with data from the evaluation of a human immunodeficiency virus (HIV) prevention program for Latino adolescents. METHODS: The onset of sexual activity, changes in the frequency of sex, and changes in the proportion of respondents with multiple partners were compared for intervention and comparison groups. Multivariate regression analysis was used to assess the effect of the intervention on these outcomes after adjustment for baseline differences between the intervention and comparison groups. RESULTS: Male respondents in the intervention city were less likely than those in the comparison city to initiate first sexual activity (odds ratio [OR] = 0.08). Female respondents in the intervention city were less likely to have multiple partners (OR = 0.06). The program promoting and distributing condoms had no effect on the onset of sexual activity for females, the chances of multiple partners for males, or the frequency of sex for either males or females. CONCLUSIONS: An HIV prevention program that included the promotion and distribution of condoms did not increase sexual activity among the adolescents in this study. PMID- 7998637 TI - Contraceptive efficacy and acceptability of the female condom. AB - OBJECTIVES: The purpose of the study was to determine the contraceptive efficacy of the female condom and to provide data about the device to the US Food and Drug Administration. METHODS: The clinical trial was conducted at six US sites and three sites in Latin America. Eligible subjects were in mutually monogamous relationships and agreed to use the female condom as their only means of contraception for 6 months. RESULTS: A total of 328 subjects contributed to the analysis of contraceptive efficacy. Twenty-two US subjects and 17 Latin American subjects became pregnant, yielding 6-month gross cumulative accidental pregnancy rates of 12.4 and 22.2, respectively. During perfect (consistent and correct) use of the method, the 6-month accidental pregnancy rates were 2.6 and 9.5 for the US and Latin American centers, respectively. There were no serious adverse events related to the use of the method. CONCLUSIONS: The female condom provides contraceptive efficacy in the same range as other barrier methods, particularly when used consistently and correctly, and has the added advantage of helping protect against sexually transmitted diseases. PMID- 7998638 TI - The consistency of self-reported HIV risk behavior among injection drug users. AB - OBJECTIVES: Most studies of risk factors for human immunodeficiency virus (HIV) rely heavily on retrospective self-reports. The degree to which these reports provide reliable information has received little research attention. The purpose of this study was to assess the extent to which the reliability of retrospective self-report data is affected over time. METHODS: Data were examined from a longitudinal study of risk behaviors among injection drug users. Structured interviews were administered to 366 injection drug users who were asked to recall behaviors that they had reported 6, 12, or 18 months earlier. RESULTS: Kappa coefficients showed moderate initial memory loss for injection and sexual risk behaviors. After 6 months, time had little effect on the ability of injection drug users to recall injection and sexual risk behaviors. For ordinal measures of risk, subjects who gave different reports over time were most likely to disagree by one response category. CONCLUSIONS: These findings support the use of retrospective self-reports in assessing HIV risk behaviors among injection drug users. Retrospective inquiry is likely to remain an important method for collecting data over time. PMID- 7998639 TI - The types of drugs used by HIV-infected injection drug users in a multistate surveillance project: implications for intervention. AB - OBJECTIVES: This study sought to describe the drugs used by drug injectors infected with human immunodeficiency virus (HIV) and to determine factors associated with the primary injection drug used. METHODS: A cross-section of persons 18 years of age or older reported with HIV or acquired immunodeficiency syndrome (AIDS) to local health departments in 11 US states and cities was surveyed. RESULTS: Of 4162 persons interviewed, 1147 (28%) reported ever having injected drugs. Of these 1147 injectors, 72% primarily injected a drug other than heroin. However, the types of drugs injected varied notably by place of residence. Heroin was the most commonly injected drug in Detroit (94%) and Connecticut (48%); cocaine was the most common in South Carolina (64%), Atlanta (56%), Delaware (55%), Denver (46%), and Arizona (44%); speedball was most common in Florida (46%); and amphetamines were most common in Washington (56%). Other determinants of the type of drug primarily injected were often similar by region of residence, except for heroin use. Polysubstance abuse was common; 75% injected more than one type of drug, and 85% reported noninjected drug use. CONCLUSIONS: Preventing the further spread of HIV will require more drug abuse treatment programs that go beyond methadone, address polysubstance abuse, and adapt to local correlates of the primary drug used. PMID- 7998641 TI - The incidence of defensive firearm use by US crime victims, 1987 through 1990. AB - It is well known that many crimes in the United States are committed with firearms. Less adequately documented is the frequency with which victims use guns in self-defense. We used National Crime Victimization Survey data to examine incidents where victims employed guns against offenders. Between 1987 and 1990 there were an estimated 258,460 incidents of firearm defense, an annual mean of 64,615. Victims used firearms in 0.18% of all crimes recorded by the survey and in 0.83% of violent offenses. Firearm self-defense is rare compared with gun crimes. PMID- 7998640 TI - Correlates of employment after AIDS diagnosis in the Boston Health Study. AB - OBJECTIVES: The purpose of this study was to determine the impact of personal and job characteristics on the time to employment loss after diagnosis of the acquired immunodeficiency syndrome (AIDS) and to examine how job loss affects patients' income. METHODS: Data were collected from 305 patients with AIDS at three sites in Boston, Mass, between February 1990 and July 1991. Life-table methods were used to estimate the number of months employed after diagnosis. A Cox proportional hazards model was used to estimate the effect of risk factors on the probability of ceasing employment in a month. RESULTS: Seventy-six percent of respondents were working at the time of diagnosis; 53% still had a job at the time of the baseline interview, which averaged 16 months later, but about one in three was on sick or disability leave. Mental and physical demands of jobs significantly influenced the likelihood of employment loss. The loss of earnings reduced monthly income by 75%. CONCLUSIONS: Job characteristics affect the likelihood of employment loss, which in turn has a deleterious effect on income. Programs supporting persons with AIDS during the transition out of work or enabling them to modify their job demands may also reduce these problems. PMID- 7998642 TI - Who is Hispanic? Definitions and their consequences. AB - What is the appropriate method for classifying Spanish-speaking-origin inhabitants of the United States? This paper presents relevant data from the first wave of a longitudinal study of adolescents in the greater Miami area. As expected, the broadest definition--"up to third generation" Hispanic--identified the largest proportion of the sample as Hispanic, whereas parent self-report placed the smallest proportion into the Hispanic category. When policymakers are concerned about enumerating the entire Hispanic population, a definition broader than self-identification should be used; in estimating prevalence rates, however, the use of self-identification may be adequate. PMID- 7998643 TI - A rapid public health response to a cryptic outbreak of cholera in Hawaii. AB - In November 1991, toxigenic Vibrio cholerae O1 infection was confirmed in two unrelated persons in Hawaii. Cholera had not been acquired in Hawaii since 1895. To determine the source and extent of V cholerae O1 infections in Hawaii, both patients were interviewed, suspect food sources were investigated, and surveillance of physicians, laboratories, hospitals, and sewage treatment plants was instituted. One patient's husband had serologic titers consistent with recent V cholerae O1 infection; no other cases were confirmed and V cholerae O1 was not recovered from active surveillance of laboratories or sewage treatment plants. The investigation demonstrated that the outbreak had affected few persons and had ended. PMID- 7998644 TI - A decline in HIV-infected needles returned to New Haven's needle exchange program: client shift or needle exchange? AB - The New Haven needle exchange program experienced a significant decline in the fraction of returned needles containing human immunodeficiency virus 1 (HIV-1) proviral DNA. Is this decline due to the operations of the needle exchange or to a shift in clients? Analysis of demographic and behavioral data revealed that only one variable, the race of participating clients, changed significantly over time. However, HIV-1 prevalences in needles given to Whites and to non-Whites were not statistically different. Thus, client shift cannot be responsible for the decline in the observed HIV prevalence in needles. Instead, needle circulation times were a significant predictor of HIV prevalence. PMID- 7998645 TI - Predicting the effect of the Oregon Health Plan on Medicaid coverage for outpatients with HIV. AB - The Oregon Health Plan, which took effect in February 1994, extends Medicaid eligibility but limits coverage to conditions and treatments above a certain threshold on a prioritized list. Retrospective analysis was conducted on records of visits to two Oregon human immunodeficiency virus (HIV) outpatient clinics in 1991 and 1992 to determine Medicaid coverage if the plan had been operational. Of 1129 patients, 21.1% were Medicaid-eligible; an additional 56.5% would have been eligible under the Oregon plan. Only 5.0% to 6.8% of these patients' visits were for conditions listed below the plan's coverage threshold; almost none of these were for HIV-specific conditions. PMID- 7998646 TI - Changes in insurance status and access to care for persons with AIDS in the Boston Health Study. AB - The purpose of this study was to measure unmet needs and changes in insurance status for persons with acquired immunodeficiency syndrome (AIDS). Thirty-six percent of the study's Boston-area respondents (n = 305) had a change in insurance coverage between AIDS diagnosis and interview. Medicaid coverage increased from 14% to 41%. Pneumocystis carinii pneumonia prophylaxis was nearly universal. Only 5% did not receive zidovudine, and intravenous drug users were at higher risk. Approximately 14% to 15% of patients reported problems in obtaining medical and dental services; Blacks, homeless persons, and those who were not high school graduates were at higher risk. Use of selected treatments for which there were clear clinical guidelines was adequate, yet disadvantaged groups were more likely than other persons with AIDS to face obstacles to other services. PMID- 7998647 TI - HIV infection, risk behaviors, and depressive symptoms among Puerto Rican sex workers. AB - This paper examines the association of depressive symptoms with human immunodeficiency virus (HIV) infection and risk behaviors among 127 sex workers. Data were obtained by a structured interview and blood specimens tested for HIV. Findings showed a high prevalence rate of depressive symptoms for all sex workers regardless of HIV infection status. Results of a logistic regression analysis indicated that the use of injected drugs and engaging in unprotected intercourse with clients were strongly associated with a high level of depressive symptoms. PMID- 7998649 TI - Anonymous HIV testing: the impact of availability on demand in Arizona. AB - The purpose of this study was to evaluate the impact of anonymous testing availability on human immunodeficiency virus (HIV) test demand in Arizona. Testing patterns before and after the introduction of anonymous testing were compared. Client knowledge of new test policy and delay in testing until an anonymous option was available were assessed. Test numbers among men who have sex with men showed a statistically significant increase after introduction of an anonymous testing option. Arizona continues to maintain anonymous testing availability. Public health agencies should consider how test policy may influence people's HIV test decisions. PMID- 7998648 TI - Extramarital sex and HIV risk behavior among US adults: results from the National AIDS Behavioral Survey. AB - Data from the National AIDS Behavioral Survey were used to examine the social distribution of extramarital sex and risk for human immunodeficiency virus (HIV) infection among married individuals in the United States. Of 1686 married respondents living across the United States, 2.2% reported extramarital sex; of 3827 married respondents living in 23 urban areas with large Hispanic or African American populations, 2.5% reported having sexual partners outside marriage. The data indicate that the correlates of extramarital sex varied by race/ethnicity. Low levels of condom use were found among people reporting extramarital sex (8% to 19% consistent users). PMID- 7998651 TI - The troubadours: singing their stories of love and health. PMID- 7998650 TI - Policies of containment: immigration in the era of AIDS. AB - The US Public Health Service began the medical examination of immigrants at US ports in 1891. By 1924, national origin had become a means to justify broad-based exclusion of immigrants after Congress passed legislation restricting immigration from southern and eastern European countries. This legislation was passed based on the alleged genetic inferiority of southern and eastern Europeans. Since 1987, the United States has prohibited the entrance of immigrants infected with the human immunodeficiency virus (HIV). On the surface, a policy of excluding individuals with an inevitably fatal "communicable disease of public health significance" rests solidly in the tradition of protecting public health. But excluding immigrants with HIV is also a policy that, in practice, resembles the 1924 tradition of selective racial restriction of immigrants from "dangerous nations." Since the early 1980s, the United States has erected barriers against immigrants from particular Caribbean and African nations, whose citizens were thought to pose a threat of infecting the US blood supply with HIV. PMID- 7998652 TI - Weapon-related injury surveillance in the emergency department. PMID- 7998653 TI - Condom use and risk factors for HIV-1 infection among female commercial sex workers in Thailand. PMID- 7998654 TI - Three-year follow-up of an HIV risk-reduction intervention that used popular peers. PMID- 7998655 TI - Clarification on the coding of hip fractures. PMID- 7998656 TI - A computerized surveillance system for disease outbreaks in Oklahoma. PMID- 7998657 TI - Primary ciliary dyskinesia (the immotile cilia syndrome). AB - OBJECTIVE: The purpose of this review is to familiarize the reader with the genetic aspects, clinical manifestations, diagnostic techniques and management of the primary ciliary dyskinesia syndrome. Further, this article illustrates some unusual features of this syndrome and discusses some speculative hypotheses concerning its pathogenesis and clinical presentation. DATA SOURCES: The bibliography includes references in English as well as some references of historical interest in German. Both human and veterinary literature are quoted. Sources included computerized bibliographic searches of recent literature and reviews of literature. STUDY SELECTION: Selection of papers was made based on their historic importance in the definition and characterization of the disease, and on reviews of large bodies of novel or interesting information. Some review papers were not included to avoid repetition. RESULTS: Although the incidence of primary ciliary dyskinesia is low, the inclusion of this condition in the differential diagnosis of chronic and recurrent sinobronchial disease in children and older individuals is very common. Primary ciliary dyskinesia should be suspected in individuals who present chronic respiratory symptoms already in the neonatal period, develop profuse, chronic mucopurulent rhinorrhea, and chronic otitis media and sinusitis. Chronic cough, obstructive lung disease, and bronchorrhea associated with the aforementioned manifestations should also make clinicians suspect this syndrome. Male sterility is almost universally present and situs inversus is present in 50% of affected persons. The diagnosis of primary ciliary dyskinesia is clinical and is confirmed by studies of ciliary motility and ultrastructure of the respiratory mucosa. Management is directed to microbial suppression by frequent antibiotic administration, and to clearing of retained secretions. CONCLUSIONS: The diagnosis of primary ciliary dyskinesia requires familiarity with the clinical picture and the specific techniques of identification. Although the basic mechanism of disease is known, the molecular genetics of primary ciliary dyskinesia and the causes for the phenotypic variability remain to be explained. Future research should be directed to the identification of the gene(s) responsible for the manifestations of the disease and to effective methods of activation, in vivo, of dysfunctional cilia. PMID- 7998658 TI - Cardiac tamponade and recurrent upper respiratory tract infections in a 22-year old woman. AB - The association of IgA deficiency with SLE is clearly established but occurs in only a small percentage of patients. Several hypotheses address the relationship between the two disease processes but the common link remains undetermined. It is important to investigate the diagnosis of IgA deficiency in patients presenting with SLE in order to provide the most appropriate treatment. This patient not only represents a rare presentation of SLE but highlights the uncommon occurrence with IgA deficiency and brings forth valuable teaching points of both diseases. PMID- 7998659 TI - Outcome of cough variant asthma treated with inhaled steroids. AB - BACKGROUND: Cough variant asthma is defined as a persistent nonproductive cough with minimal wheezing or dyspnea. The uncontrolled coughing may interfere with sleep, work, and social activities. Cough precipitating fecal or urinary incontinence can be extremely distressing. The diagnosis is established within 1 to 2 weeks by a trial of prednisone, 30 mg a day. The cough will be controlled within that time and subsequent management can consist of inhaled corticosteroids. OBJECTIVE: To evaluate the course of ten patients with cough variant asthma and their response to inhaled corticosteroids. METHODS: Retrospective analysis of the presentation, diagnosis, course, and response to oral and inhaled steroids in ten patients with cough variant asthma. RESULTS: Ten patients whose chief complaint was persistent debilitating cough for periods of 2 months to 20 years underwent a diagnostic and therapeutic trial of prednisone as previously described. At a mean follow-up period of 28 months all were free of debilitating cough. Eight of ten patients were still receiving inhaled steroids and two needed low dose alternate day oral steroid therapy. Two patients had complete remission of symptoms. None required daily inhaled or oral bronchodilators and there were no hospital admissions for respiratory symptoms. CONCLUSIONS: Inhaled corticosteroid therapy after a diagnostic trial of oral steroids is effective for long-term control of cough variant asthma. PMID- 7998660 TI - Insect sting allergy: analysis of a cohort of patients who initiated venom immunotherapy from 1978 to 1986. AB - BACKGROUND: The proper duration of venom immunotherapy remains uncertain. OBJECTIVE: We report our experience with a cohort of patients who started venom immunotherapy from 1978 to 1986. METHODS: In a midwestern allergy practice, the cohort of 204 stinging insect-allergic patients who commenced venom immunotherapy from 1978 to 1986 were identified and evaluated by retrospective chart analysis and patient telephone inquiry. RESULTS: Only 12 patients remain on venom treatment. The majority of patients have discontinued venom immunotherapy either by self-determination (35 patients) or upon physician advice (80 patients). There was no relationship between the severity of the initial sting reaction and the length of time patients received therapy. After cessation of venom treatment, there were 148 re-stings in 117 patients with only two re-sting reactions, both of which occurred in patients with severe initial sting reactions. CONCLUSIONS: Most patients who have received four to 6 years of venom immunotherapy continue to tolerate insect stings after cessation of treatment. PMID- 7998662 TI - Psyllium hypersensitivity. AB - BACKGROUND: Psyllium-containing laxatives are used by 4 million Americans daily. Dietary supplements for the management of hypercholesterolemia and for prevention of colon cancer make up additional uses of this plant fiber. OBJECTIVE: To assess a patient in an HMO practice with allergic cutaneous and respiratory findings associated with chronic psyllum ingestion and review information on psyllium hypersensitivity. METHODS: Clinical and laboratory evaluation of the patient and literature review through MEDLINE. RESULTS: Two years after initiating regular psyllium-containing laxative use a 40-year-old woman presented with a pruritic macular, papular, and urticarial rash involving the entire body including the palms, soles, and oropharynx sparing only the face. There was an associated sensation of chest and throat tightness and lip swelling. The signs and symptoms resolved upon discontinuance of the psyllium and recurred immediately after the patient initiated a challenge test. The total serum IgE was elevated and the modified RAST for psyllium-specific IgE was positive (Plantago ovata antigen). CONCLUSIONS: The allergens in psyllium appear to be protein in nature and derived from the inner seed endospore and embryo rather than from the husk itself. The patient described herein was sensitized and challenged via ingestion. PMID- 7998661 TI - Lack of adverse reactions to measles, mumps, and rubella vaccine in egg-allergic children. AB - BACKGROUND: Controversy exists regarding allergic reactions to measles, mumps, and rubella (MMR) vaccine in egg-allergic patients. To date there have been only isolated reports describing egg-allergic patients with anaphylaxis to MMR vaccine. OBJECTIVE: Our study was designed to monitor possible adverse reactions in egg-allergic children receiving MMR vaccine. METHODS: Initially prick and intradermal testing with MMR vaccine was carried out. The first 120 children were screened in this fashion, with frequent irritant reactions occurring with skin testing but no subsequent reactions when full-strength vaccine was administered. The subsequent 380 children received the undiluted MMR vaccine without prior skin testing. DESIGN: Over an 8-year period, MMR vaccine was given to 500 egg-allergic children in outpatient setting. RESULTS: No anaphylactic reactions were observed in any of the 500 children immunized with MMR vaccine. Five children showed minor rashes within two hours of administration of the MMR vaccine. CONCLUSIONS: It is therefore felt the previously reported adverse reactions to MMR vaccine represent reactions to other vaccine components rather than the suspected egg antigens. The presence of egg allergy should therefore not be considered a contraindication to MMR immunization. PMID- 7998663 TI - Augmented interleukin-6 secretion in collagen-stimulated peripheral blood mononuclear cells from patients with systemic sclerosis. AB - BACKGROUND: Systemic sclerosis is an autoimmune disease that is associated with excessive fibroblast proliferation and collagen deposition in various tissues. Interleukin-6 (IL-6) is produced by fibroblasts, activated T and B lymphocytes, which maybe involved in the pathogenesis of systemic sclerosis. OBJECTIVE: This study was performed in order to determine whether IL-6 could be detected specifically in collagen-stimulated peripheral blood mononuclear cells from patients with systemic sclerosis. METHODS: We clinically evaluated seven patients with systemic sclerosis for disease duration and organ involvement and analyzed in vitro the ability of their peripheral blood mononuclear cells and those of disease-free controls, in the presence of concanavalin A, human type I collagen, and the mast cell mediator, heparin to secrete IL-6 spontaneously by a sensitive ELISA. RESULTS: Interleukin-6 production by nonspecific stimulation with concanavalin A did not differ between patients with systemic sclerosis and controls; however, collagen stimulation significantly increased IL-6 production in patients with systemic sclerosis; mean 1728 pg/mL versus a mean of 386 pg/mL in controls P = < .05). Collagen-stimulated IL-6 levels > 2000 pg/mL were obtained in 86% of patients with systemic sclerosis compared with none in the controls. In patients with systemic sclerosis with a shorter disease duration, greater spontaneous as well as collagen- and heparin-stimulated IL-6 production was observed, whereas decreased IL-6 levels were noted with longer disease duration (> 21 years). CONCLUSIONS: The results of this study suggest that peripheral blood mononuclear cells from patients with systemic sclerosis are specifically sensitized to human type I collagen to produce increased levels of IL-6, which may play a role in the pathogenesis in this fibrotic disorder. PMID- 7998664 TI - Budesonide and terfenadine, separately and in combination, in the treatment of hay fever. AB - BACKGROUND: While hay fever is a very common experience, its treatment in primary care setting has been little reported in controlled studies. OBJECTIVE: This study sought to evaluate the patient's assessment of efficacy of an intranasal steroid spray (budesonide) alone or in combination with an antihistamine (terfenadine) against terfenadine alone or placebo alone. METHODS: A double-blind parallel group, placebo-controlled trial design was used, comparing the four groups. Each group used an active or placebo spray and active or placebo tablets. Symptom scores were recorded daily in diaries over a 21-day period. RESULTS: Overall assessment of efficacy by the 106 patients was significantly greater (P < .05) for budesonide versus terfenadine or placebo alone. There was a 40% placebo response. Budesonide was more effective than terfenadine for all individual symptom scores, particularly nasal blockage, against which terfenadine was ineffective. Adverse effects were mild and transient for all groups. CONCLUSIONS: Budesonide alone is a highly effective treatment for hay fever with few side effects. PMID- 7998665 TI - Anaphylaxis due to limpet ingestion. AB - BACKGROUND: The limpet, phylum Mollusca, is one of the most frequent sea mollusks in the Canary Islands. Limpet IgE hypersensitivity reactions have been described. OBJECTIVE: To describe six patients with anaphylactic reactions due to limpet ingestion and to demonstrate by in vivo methods and by in vitro techniques specific IgE responses. METHODS: Six subjects who developed severe bronchospasm 30 to 120 minutes after eating limpets were included in the present study. The antigenic material for the in vivo and in vitro studies was an extract of cooked limpet prepared in our laboratory. Skin prick tests were performed in all patients using commercially available aeroallergens, mollusk, and crustacean extracts; the same skin tests were performed using the extracts prepared in our laboratory. Specific IgE by CAP and RAST and CAP inhibition studies were also performed. Limpet contamination by mites was excluded through a commercial ELISA using monoclonal antibodies. RESULTS: All patients had positive skin prick tests to D. pteronyssinus and cooked limpet extract and weak reactivity to cockroach and raw limpet extract. Specific IgE to mites and cooked limpet extract was also found using CAP and RAST techniques, respectively. The possible existence of common epitopes between limpet and D. pteronyssinus was excluded by CAP inhibition studies. Finally, no significant mite concentration was detected in the cooked limpet extract analyzed by a commercially available ELISA. CONCLUSIONS: Limpet is a potentially dangerous allergen specially in patients sensitized to D. pteronyssinus. PMID- 7998666 TI - Use of nasal cytology in the diagnosis of occult chronic sinusitis in asthmatic children. AB - BACKGROUND: Chronic sinusitis, in contrast to acute sinusitis, often presents with nonspecific symptoms that may be confused with other disease entities. Due to the cost of computerized tomography and the difficulty in interpreting sinus radiographs in certain children, a search for a simpler screening tool for chronic sinusitis in children was undertaken. OBJECTIVE: This study was undertaken to provide a quantitative comparison between the methods of wax paper blow and Rhinoprobe scraping for nasal cytology in screening for chronic sinusitis while minimizing selection bias. METHODS: Twenty serially selected patients (13 males and seven females) with a mean age of 11 years (range 6-16) were enrolled. Nasal cytology was obtained via two methods: scraping of the turbinate with a Rhinoprobe (Synbiotics Inc.,) and wax paper blow. RESULTS: The results showed that > or = 5 neutrophils per high power field on Rhinoprobe cytology significantly correlated with radiographic sinusitis (P < .05 by Chi square and P < .056 by Fisher's exact test). The sensitivity and specificity for > or = 5 neutrophils per high power field were 100% and 53%, respectively. Counts of other nasal cells, such as eosinophils, bacteria, and epithelial cells, did not yield significant correlations with radiographic sinusitis. CONCLUSIONS: We feel that the Rhinoprobe, with criteria of > or = 5 neutrophils per high power field, may be useful as a screen for occult chronic sinusitis in childhood asthma. Confirmation of sinusitis via X-ray is still necessary if neutrophils are present on Rhinoprobe nasal cytology. PMID- 7998667 TI - Comparison of budesonide and disodium cromoglycate for the treatment of seasonal allergic rhinitis in children. AB - BACKGROUND: Budesonide and disodium cromoglycate (DSCG) are commonly used agents for the treatment of seasonal allergic rhinitis. The comparative efficacy, however, of these agents in the pediatric population has not been reported. OBJECTIVE: The efficacy of nasally administered budesonide (400 micrograms/day, administered twice daily) was compared with that of DSCG (31.2 mg/day, administered six times per day) for the treatment of seasonal allergic rhinitis in children. METHODS: A single-blind parallel group study was carried out in 56 children (mean age 12 years) with seasonal allergic rhinitis. Treatment was for 3 weeks, during which patients assessed nasal symptoms, eye symptoms, and overall efficacy. RESULTS: Over the 3-week period, mean scores for the nasal symptoms of blocked nose, itchy nose, and sneezing were significantly lower with budesonide therapy than with DSCG. P values were .021, .0032, and .0016, respectively. Both treatment groups reported reduced scores for runny nose and eye symptoms; no statistically significant difference was observed between budesonide and DSCG. The global efficacy assessment scores show significantly more patients benefited from budesonide therapy than from DSCG treatment. CONCLUSIONS: The results suggest that nasally administered budesonide has greater efficacy than DSCG in the treatment of seasonal allergic rhinitis in children. PMID- 7998668 TI - Immunologic findings in confectionary workers. AB - BACKGROUND: Food allergies are frequent in the general population. There are however, few studies of immunologic responses among workers in the confectionary industry. OBJECTIVE: To assess immunologic and clinical findings of workers in a confectionary plant. METHODS: Immunologic (skin tests and serum IgE) and respiratory findings (symptoms and lung function) were studied in a group of 71 confectionary workers (mean age: 35 years and mean exposure: 11 years). RESULTS: Skin prick testing with food extracts used in the manufacturing of candies and pastries demonstrated that the most frequent positive skin reaction occurred with extracts of cacao (31%), followed by reactions to chocolate (9%), cocoa (6%), hazelnut (6%), and sugar (2%). Increased serum IgE levels were found in 13.0% and increased IgM serum levels in 52.1% of these confectionary workers. The prevalence of asthma (26.1%) and dyspnea (26.1%) in workers with positive skin tests was significantly higher than in workers with negative skin tests (asthma: 2.0%, P = .004; dyspnea: 4.1%, P = .001). There was a high prevalence of acute respiratory symptoms during the work shift, but no significant association with immunologic tests was found. Similarly, both skin test positive and skin test negative workers exhibited significant across shift changes in lung function; however, no significant differences in baseline lung function or across-shift changes were noted between skin test positive and negative workers. Pre-shift administration of disodium cromoglycate (DSCG) significantly diminished across shift reductions in FEF50 and FEF25 for both skin test positive and skin test negative workers. CONCLUSIONS: These data suggest that exposure to environmental factors in confectionary plants is associated with frequent respiratory symptoms of an irritative nature. Specific skin testing may be useful in characterizing confectionary workers at risk for the development of occupational asthma. PMID- 7998669 TI - Objective measurements of compliance in asthma treatment. AB - BACKGROUND: Self-management protocols and home peak expiratory flow rate monitoring are thought to improve asthma care. OBJECTIVE: Compliance and accuracy of patients' record keeping were measured during a guided self-management protocol. Video, face-to-face instruction, and written protocols were part of the educational program. METHODS: Twenty patients participated in a 5-week study using memory capable peak expiratory flow rate meters and inhalers. During the baseline week all patients followed their customary approach to treatment and kept written diaries of peak expiratory flow rate and inhaler usage results; thereafter, they followed an individually designed self-management protocol. RESULTS: Good technique and knowledge were found during the baseline visit and improved by the last visit. Compliance with the protocol during the fifth week occurred in 40% of patients with underusage of inhalers in 50% and overusage in 10% despite allowing for a 10% inaccuracy in recording. Patients keeping inaccurate records early in care tend not to improve. Errors in recording inhaler usage increased from 47% to 58% of days during the final week. Patients inflated peak expiratory flow rate scores (P < .01) over time. Slight improvement in the peak expiratory flow rate was found for the entire group (baseline week 371 L/min versus final week 386 L/min P < .05). CONCLUSIONS: Despite an extensive educational program in the self-management of asthma, compliance with recommended treatment was only 40%. Electronic monitoring of peak expiratory flow rate and inhaler usage can provide early identification of patients who do not comply. PMID- 7998671 TI - [Titrimetric measurement of catalytic concentration of pancreatic lipase: state of the art]. AB - Most lipase routine assays are carried out using either soluble substrates or emulsified substrates (triglycerides or olive oil) at low concentrations. Many of these techniques require a secondary standard, which must be titrated beforehand; the need for a reference method is thus compelling. Titrimetric assays have several advantages such as the possibility of employing high substrate concentrations allowing the direct determination of the product of lipolysis in the absence of interfering phenomena. In a recent study it was demonstrated that human lipase activity depends on the zeta-potential of the lipid droplets, the number of hydroxy groups present in each individual bile salt, the aggregation number and the conjugation of bile salts with taurine or glycine. Hydroxypropyl methylcellulose proposed by Tietz et al is to be preferred to gum arabic for being a pure, well defined emulsifier. Ultrasonic homogenizers enable volumes of oil-in-water emulsions, characterized by fine lipid droplets with good homogeneity to be obtained without overheating. Lipolytic activity is completely inhibited by 70 mmol/l of bile salt (regardless of the type) in the absence of colipase. Variable concentrations of colipase are needed to restore the lipase activity in the presence of different bile salts: optimal cofactor concentrations vary from 0.1 mg/l with deoxycholate or cholate to 6 mg/l with taurocholate or glycocholate. Even after optimization of the medium with colipase, marked differences in enzyme activity are noted depending on the bile salt used.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7998670 TI - [Glycated hemoglobin: assay methods and problems of standardization]. AB - Glycated hemoglobin can be assayed by methods using different principles, whose performances vary and are difficult to control. The most widely used techniques measure either specifically glycated A1c hemoglobin (HbA1c) or total glycated hemoglobin. They are reviewed in detail in this paper and standardization problems due to the absence of reference materials and methods are discussed. HbA1c seems to be considered the most significant parameter for monitoring diabetic control. Standardization of the assays, calibrated with reference to this parameter, could be performed provided there is strict control of the methods performance. PMID- 7998672 TI - [In vivo study of the antilipoperoxidant effect of 3',5,7-trihydroxy-4'-methoxy flavone 7 rutinoside]. AB - In 3-month-old Wistar rats carrageenan and CCl4 injected intraperitoneally induce an acute phase reaction which is characterized by a marked increase in alpha 1, alpha 2, beta serum globulins. This reaction corresponds to a large increase in these globulins in the first case and a smaller one in the second. A lipoperoxidant effect is demonstrated by the serum lipoprotein mobility as the lipoperoxidation index (in MDA units) or the decrease in serum vitamin A and E concentrations. This effect is also greater in the first case than in the second one. In the same way the lipoperoxidant effect is shown in liver microsomes but with a lower amplitude in the first case than in the second one. The treatment of rats by intraperitoneal injection of diosmine (150 mg/kg per week) during the 8 weeks which precede the injection of carrageenan or CCl4 results in: i) a marked decrease in the acute-phase reaction and a lower one in the lipoperoxidant effect, in serum; ii) a decrease in the CCl4 induced lipoperoxidant effect in liver microsomes. It may be concluded that diosmine, not injected at the same time as carrageenan or CCl4, but during the previous 8 weeks is sufficiently well distributed in the whole body to produce a marked inhibition of the acute phase reaction and a perceptible effect on lipoperoxidation. It may be considered an effective complement to the natural antioxidant defences of the organism (vitamins A and E). PMID- 7998674 TI - [Evaluation of a new commercial kit for emergency determination of serum myoglobin]. AB - The usefulness of a nephelometric-based serum myoglobin assay kit in the early diagnosis of acute myocardial infarction was assessed in 92 consecutive patients admitted within 24 hours of the onset of spontaneous chest pain lasting > or = 20 minutes. The discharge diagnosis was acute myocardial infarction in 37 patients (40.2%), myocardial infarction lasting > or = 6 hours in 10, and no myocardial infarction in 45 (48.9%). The characteristic curve showed that the best differential diagnostic value was a serum myoglobin > or = 130 micrograms/l (sensitivity, 75.6%; specificity, 91.7%; positive-predictive value, 88%; negative predictive value, 82%). The initial diagnosis was doubtful in 33 patients (36%) because of an inconclusive electrocardiogram. A serum myoglobin value of > or = 130 micrograms/l would have identified 9 of the 13 patients with acute myocardial infarction and all of the 20 patients without myocardial infarction, giving an accuracy of 84.8%. These results suggest that this new rapid, quantitative serum myoglobin assay would be useful in the evaluation of suspected myocardial infarction, especially in patients with an inconclusive electrocardiogram. PMID- 7998673 TI - [Determination of lipoproteins defined following their apolipoprotein composition for the prediction of cardiovascular risk]. AB - Immunological methods permit separation and measurement of lipoprotein concentrations in terms of their apolipoprotein composition. We have elaborated two different methods to measure lipoprotein particles in plasma. The first is a selective bi-site Elisa procedure and the second a differential electroimmunoassay. Lp A-I plays an essential role in reverse cholesterol transport. We have shown that Lp A-I is an anti-risk marker of atherosclerosis. Its concentration is higher in females than in males, it is decreased in patients with coronary heart disease and in their kindreds and in populations with a high cardiovascular risk. This fraction is increased in octogenarians. In pharmacological terms, HMG CoA reductase inhibitors increase Lp A-I and Lp A-I:A II while fenofibrate decreases Lp A-I and increases Lp A-I:A-II. These studies demonstrate that the measurement of lipoprotein concentrations according to their apolipoprotein composition can reveal lipoprotein fractions that have precise metabolic roles with epidemiological and pathophysiological implications. PMID- 7998675 TI - Reference materials in clinical enzymology: preparation, requirements and practical interests. AB - Five enzyme materials (gamma-glutamyltransferase, alkaline phosphatase, creatine kinase, alanine aminotransferase and prostatic acid phosphatase) are currently certified using a reference method. Furthermore, feasibility studies have been performed for four other enzymes (aspartate aminotransferase, lactate dehydrogenase, amylase and lipase). They indicated that these enzymes can be purified and stabilized, but the materials have not yet been certified. This shows that the most important enzymes in clinical laboratories can be purified, and stabilized, without significant alteration of their catalytic properties. By carefully choosing a matrix, the commutability of these enzyme preparations and patients' samples between some methods, including routine methods, may be preserved. Thus, these materials can be used to calibrate the routine methods in terms of the corresponding reference methods after commutability has been verified. Current studies suggest that this objective can be reached, provided three criteria are satisfied: i) the calibrated and reference methods must be of equal specificity; ii) the enzyme calibrator should be, as closely as possible, identical to the human analyte enzyme in its native matrix (eg serum); iii) and the inter-method ratio should be constant (within the limits of experimental error) for the enzyme calibrator and for all patients' samples. PMID- 7998677 TI - Cellular communications and cell-matrix interactions in the pathogenesis of fibroproliferative diseases: liver fibrosis as a paradigm. AB - In vitro and in vivo studies suggest a strong cooperation between hepatocytes and mesenchymal cells and between the different non-parenchymal cell types in liver injury and fibrogenesis. The fibrogenic reaction might be described as a dynamic cascade of mechanisms beginning with hepatocyte necrosis and followed by inflammation, activation of macrophages, release of fibrogenic mediators, activation of fat-storing cells, stimulated extracellular matrix synthesis, and diminished matrix degradation resulting in a net matrix accumulation. In detail the initial events of hepatocyte injury and necrosis are followed by local proliferation of Kupffer cells, by influx of blood macrophages and by an aggregation of platelets in necroinflammatory areas. Through phagocytosis and endotoxin challenge, macrophages are activated and convert molecular oxygen into radicals and hydrogen peroxide which might be deleterious to hepatocytes. Furthermore, activated Kupffer cells and degranulating platelets release a number of polypeptide growth regulators stimulating thus fat-storing cell proliferation (transforming growth factor (TGF) alpha/epidermal growth factor, platelet-derived growth factor), transformation into myofibroblasts (transforming growth factor beta, tumor necrosis factor (TNF) alpha) and extracellular matrix synthesis of fat-storing cells and myofibroblasts (TGF-beta, TGF-alpha TNF-alpha). An impressive amount of literature exists demonstrating the central role of fat storing cells and of its transformed counterpart, ie the highly active and synthetic myofibroblasts in fibrogenesis. These cells produce the majority of the extracellular matrix components, eg collagens, proteoglycans, glycoproteins, and hyaluronan. They have the ability to stimulate themselves via production of growth regulators in an autocrine way. The multiple interactions of the different cells involved in fibrogenesis, the findings that combinations of growth regulators may act additively, synergistically or antagonistically, the fact that certain growth regulators induce the synthesis or receptor expression of others and even of themselves and, findings suggesting an interaction between growth regulators, cell surface receptors, binding proteins (scavengers) and extracellular matrix components indicate a very complex network in fibrogenesis. To get further inside these complicated mechanisms, experimental designs that provide better images of the in vivo situation than conventional techniques used presently are required. PMID- 7998678 TI - International Federation of Clinical Chemistry (IFCC). Molecular biology techniques in the diagnosis of monogenic diseases. PMID- 7998676 TI - Generation of superoxide radicals as byproduct of cellular respiration. AB - Cell respiration is associated with the risk of formation of oxygen radicals. Although various conditions of respiration have been described under which O2 radicals are generated it is not clear whether oxygen radical generation is an inevitable side effect of respiration. The answer is necessarily linked to an understanding of the mechanism and molecular site of oxygen radical generation. Redox-cycling ubiquinones of the mitochondrial respiratory chain have often been suggested to account for cellular O2-radical formation. However, there is an increasing body of evidence which refutes this assumption on thermodynamic grounds. The discovery of a novel respiratory enzyme of heart mitochondria, exogenous NADH-dehydrogenase, some years ago, has considerably aided understanding of mitochondrial O2-radical generation and the role of ubiquinones therein. This mitochondrial enzyme can be directly activated by cytosolic NADH. It has been shown that NADH consumption via this enzyme not only stimulates electron flow along components of the respiratory chain but that its activity is also linked to the release O2-. or the single electron reduction of adequate non physiological oxidants. Anthraquinones which are increasingly used as antitumor drugs can enter this redox-shuttle and initiate radical chain reactions which may be partially responsible for the selective cardiotoxicity of these compounds. Metabolic conditions, causing abnormally high NADH levels in the cytosol, such as ischemia have been found to irreversibly transform intact mitochondria to active radical generators. The present review elucidates the finding of a general phenomenon which gives more insight into the mechanism and the site of O2-radical formation during normal cell respiration.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7998679 TI - Summary of a workshop on mechanisms to enhance university/industry interaction in biomedical engineering. PMID- 7998680 TI - Biased cell migration of fibroblasts exhibiting contact guidance in oriented collagen gels. AB - We present here the first quantitative correlation for cell contact guidance in an oriented fibrillar network in terms of biased cell migration. The correlation is between the anisotropic cell diffusion parameter, DA = Dx/Dy, and the collagen gel birefringence, delta n, a measure of axially biased collagen fibril orientation in the x-direction. The cell diffusion coefficients, Dx and Dy, measure the dispersal of cells in the directions coincident with and normal to the axis of fibril orientation, respectively. Three essential methodological components are involved: (i) exploiting the orienting effect of a magnetic field on collagen fibrils during fibrillogenesis to systematically prepare uniform axially oriented collagen gels; (ii) using a microscope/image analysis workstation with precise, computer-controlled rotating and translating stages to automate birefringence measurement and, along with rapid "coarse optical sectioning" via digital image processing, to enable 3-D cell tracking of many cells in multiple samples simultaneously; and (iii) employing a rigorous statistical analysis of the cell tracks to estimate the magnitude and precision of the direction-dependent cell diffusion coefficients, Dx and Dy, that define DA. We find that this measure of biased migration in contact guidance (DA) increases with increasing collagen fibril orientation (delta n) due mainly to a rapid enhancement of migration along the axis of fibril orientation at low levels of fibril orientation, and to a continued suppression of migration normal to the axis of fibril orientation at high levels of fibril orientation. PMID- 7998681 TI - A mathematical model of thrombin production in blood coagulation, Part I: The sparsely covered membrane case. AB - This paper presents the first attempt to model the blood coagulation reactions in flowing blood. The model focuses on the common pathway and includes activation of factor X and prothrombin, including feedback activation of cofactors VIII and V by thrombin, and plasma inhibition of factor Xa and thrombin. In this paper, the first of two, the sparsely covered membrane (SCM) case is presented. This considers the limiting situation where platelet membrane binding sites are in excess, such that no membrane saturation or binding competition occurs. Under these conditions, the model predicts that the two positive feedback loops lead to multiple steady-state behavior in the range of intermediate mass transfer rates. It will be shown that this results in three parameter regions exhibiting very different thrombin production patterns. The model predicts the effect of flow on steady-state and dynamic thrombin production and attempts to explain the difference between venous and arterial thrombi. The reliance of thrombin production on precursor procoagulant protein concentrations is also assessed. PMID- 7998682 TI - Instantaneous back flow through peripheral clearance of Medtronic Hall tilting disc valve at the moment of closure. AB - An investigation of the flow dynamics through the peripheral clearance (the gap formed between the occluder tip and the metal housing in the closed position) of a tilting disc heart valve at the moment of valve closure is presented. A Medtronic Hall valve in the mitral position of an in vitro experimental set up is employed to measure the transient pressure pulses near the entrance (ventricular side) and exit (atrial side) of the peripheral clearance at valve closure. Flow within the peripheral clearance is analyzed employing a two-dimensional quasisteady computational fluid dynamics model with the measured peak pressures specified as the boundary conditions inducing the flow. The valve is visualized from its inflow (atrial) side using a stroboscopic lighting technique to investigate the presence of cavitation bubbles within the clearance. The pressure measurements showed that a relatively large pressure drop exists between the entrance and the exit to the clearance for about 0.5 msec at the moment of valve closure. The numerical simulation resulted in relatively large magnitudes of wall shear stress and pressure reduction within the clearance due to the flow established by the large pressure drop between the entrance and the exit. Cavitation bubbles visualized within the peripheral clearance at higher loading rates for valve closure correlated with the presence of large pressure reduction within the clearance. Analysis of the results of this study indicates that the back flow through the clearance at the instant of valve closure may contribute toward injury to formed elements in blood in spite of the short duration of the flow. PMID- 7998683 TI - Lumped model of terminal aortic impedance in the dog. AB - The aim of this study was the formulation of a minimal lumped model of the aortic impedance as seen in the abdominal aorta just downstream of the origin of renal arteries. At this location simultaneous measurements of pressure and flow were taken in four anesthetized and open-chest dogs (weight, 30.9 +/- 5.8 kg) under basal, vasodilated (sodium nitroprusside) and vasoconstricted (methoxamine) conditions. Using these measurements we identified and compared three lumped models, A, B, and C, with decreasing complexity from A to C. The frequency response of these models was given the general form of peripheral resistance, Rp, multiplied by the ratio between (a) two zeros and two poles (model A); (b) two zeros and one pole (model B); and (c) one zero and one pole (model C). Rp was calculated as the ratio of mean pressure to mean flow. The other model parameters (time constants, damping factors, and natural frequencies) were estimated by minimizing the sum of squared differences between experimental and model generated pulsatile flows. After parameter estimation, the F-test was applied to compare the goodness of data fit obtained from the three models. Results of this test and the analysis of parameter estimation errors indicated that model B was preferable with respect to models A and C. The analysis of general model performance was followed by a consideration of alternative specific model structures that are physically realizable. With the aid of a determined model structure we evaluated the overall compliance of terminal aortic circulation under a variety of vascular states induced by injection of vasoactive agents. PMID- 7998684 TI - Simple and accurate way for estimating total and segmental arterial compliance: the pulse pressure method. AB - We derived and tested a new, simple, and accurate method to estimate the compliance of the entire arterial tree and parts thereof. The method requires the measurements of pressure and flow and is based on fitting the pulse pressure (systolic minus diastolic pressure) predicted by the two-element windkessel model to the measured pulse pressure. We show that the two-element windkessel model accurately describes the modulus of the input impedance at low harmonics (0-4th) of the heart rate so that the gross features of the arterial pressure wave, including pulse pressure, are accounted for. The method was tested using a distributed nonlinear model of the human systemic arterial tree. Pressure and flow were calculated in the ascending aorta, thoracic aorta, common carotid, and iliac artery. In a linear version of the systemic model the estimated compliance was within 1% of the compliance at the first three locations. In the iliac artery an error of 7% was found. In a nonlinear version, we compared the estimates of compliance with the average compliance over the cardiac cycle and the compliance at the mean working pressure. At the first three locations we found the estimated and "actual" compliance to be within 12% of each other. In the iliac artery the error was larger. We also investigated an increase and decrease in heart rate, a decrease in wall elasticity and exercise conditions. In all cases the estimated total arterial compliance was within 10% of mean compliance. Thus, the errors result mainly from the nonlinearity of the arterial system. Segmental compliance can be obtained by subtraction of compliance determined at two locations. PMID- 7998685 TI - Consequences of pruning in morphometry of coronary vasculature. AB - There is a paucity of data on the branching pattern and dimensions of the blood vessels in various organs. The reason for the paucity is undoubtedly the tremendous effort needed to obtain the morphometric data. For those organs whose morphometric data have been determined, pruning was introduced: cutting off branches at successive generations, measuring what remained, using the statistical data to estimate what were cut off, and adding the estimated data to the measured data to obtain the final results. Evaluation of the effects of pruning was not possible, however, because a full set of precise data did not exist. Now a complete set of morphometric data on the coronary arteries is presented by Kassab et al. (8). Hence we are in a position to evaluate pruning versus accuracy. Among several pruning protocols tried we found a simple, easy-to follow scheme that seemed to be reasonable. It reduced the labor by 79% when it was applied to the left anterior descending (LAD) artery of the pig, and it caused the following percentage errors based on comparison with the unpruned data. The largest error incurred in the mean diameters of all orders of tree is 7.6%. The corresponding maximum errors in the length and number of elements in all orders are -9.8% and 30.0%, respectively. The estimated error of the total equivalent Poiseuille's resistance for the LAD artery computed from pruned data was 25.2% when compared with that computed from unpruned data. PMID- 7998686 TI - The effect of in vitro fluoride ion treatment on the ultrasonic properties of cortical bone. AB - The mechanical properties of composites are influenced, in part, by the volume fraction, orientation, constituent mechanical properties, and interfacial bonding. Cortical bone tissue represents a short-fibered biological composite where the hydroxyapatite phase is embedded in an organic matrix composed of type I collagen and other noncollagenous proteins. Destructive mechanical testing has revealed that fluoride ion treatment significantly lowers the Z-axis tensile and compressive properties of cortical bone through a constituent interfacial debonding mechanism. The present ultrasonic data indicates that fluoride ion treatment significantly alters the longitudinal velocity in the Z-axis as well as the circumferential and radial axes of cortical bone. This suggests that the distribution of constituents and interfacial bonding amongst them may contribute to the anisotropic nature of bone tissue. PMID- 7998687 TI - A device for subjecting vascular endothelial cells to both fluid shear stress and circumferential cyclic stretch. AB - The proposal of the role of mechanical forces as a localizing factor of atherosclerosis has led many researchers to investigate their effects on vascular endothelial cells. Most previous efforts have concentrated on either the fluid shear stress, which results from the flow of blood, or the circumferential "hoop" stretch, which results from the expansion of the artery during the cardiac cycle. In fact, arterial endothelial cells are subjected to both fluid shear stress and cyclic hoop stretch in vivo. Therefore, a more complete investigation of mechanical phenomena on endothelial cell behavior should include both kinds of mechanical stimuli. This study was undertaken to design an experimental apparatus that could subject cultured vascular endothelial cells to simultaneous physiologic levels of both shear stress and cyclic hoop stretch. The experimental apparatus consists of four cylindrical elastic tubes so that the following conditions may be studied: (a) static conditions: (b) shear stress only; (c) hoop stretch only; and (d) shear stress and hoop stretch. In order to establish the functional capabilities of the apparatus, bovine pulmonary artery endothelial cells were cultured in the tubes, and their morphology and f-actin structure were observed with confocal microscopy. The cells remained healthy and attached to the walls throughout the 24 hr experiment. Preliminary results indicated that the alignment of endothelial cells subjected to shear stress was significantly enhanced by the addition of hoop strain. PMID- 7998688 TI - Comparison of adaptive filtering in time-, transform- and frequency-domain: an electrogastrographic study. AB - Adaptive cancellation of motion artifacts in the electrogastrogram (EGG) is presented in this paper. The EGG is a surface measurement of gastric electrical activity. Like other noninvasive electrophysiological measurements, the EGG contains motion artifacts. A number of papers have been published on the adaptive cancellation of motion artifacts or interferences in biomedical signals. Adaptive filtering was performed in time domain in almost all of the previous publications. In this paper, however, three different sorts of adaptive filters were investigated and their efficiencies in cancellation of motion artifacts were compared with each other. These include time-domain, transform-domain, and frequency-domain adaptive filters. A series of simulations were conducted to investigate the performance of these adaptive filters in cancellation of respiratory and motion artifacts. The results show that the frequency-domain adaptive filter has superior performance over the time- and transform-domain adaptive filters in the cancellation of stationary respiratory artifacts in the EGG. Although results focus on the EGG, this paper provides useful information for adaptive filtering of other biomedical signals. PMID- 7998689 TI - Evaluating rescaled ranged analysis for time series. AB - Rescaled range analysis is a means of characterizing a time series or a one dimensional (1-D) spatial signal that provides simultaneously a measure of variance and of the long-term correlation or "memory," The trend-corrected method is based on the statistical self-similarity in the signal: in the standard approach one measures the ratio R/S on the range R of the sum of the deviations from the local mean divided by the standard deviation S from the mean. For fractal signals R/S is a power law function of the length tau of each segment of the set of segments into which the data set has been divided. Over a wide range of tau's the relationship is: R/S = a tau H, where kappa is a scalar and the H is the Hurst exponent. (For a 1-D signal f(t), the exponent H = 2 - D, with D being the fractal dimension.) The method has been tested extensively on fractional Brownian signals of known H to determine its accuracy, bias, and limitations. R/S tends to give biased estimates of H, too low for H > 0.72, and too high for H < 0.72. Hurst analysis without trend correction differs by finding the range R of accumulation of differences from the global mean over the total period of data accumulation, rather than from the mean over each tau. The trend-corrected method gives better estimates of H on Brownian fractal signals of known H when H > or = 0.5, that is, for signals with positive correlations between neighboring elements. Rescaled range analysis has poor convergence properties, requiring about 2,000 points for 5% accuracy and 200 for 10% accuracy. Empirical corrections to the estimates of H can be made by graphical interpolation to remove bias in the estimates. Hurst's 1951 conclusion that many natural phenomena exhibit not random but correlated time series is strongly affirmed. PMID- 7998690 TI - Ultrastructure and mineral composition of urinary calculi from horses. AB - Urinary calculi from 17 horses with urolithiasis were examined to study their mineral content and ultrastructure. Among the analytic methods used were X-ray diffractometry, scanning electron microscopy, and electron microprobe analysis. The calculi initially were observed by use of a stereoscopic dissecting microscope and generally were found to have nodular surfaces surrounding a banded or granular-to-chalky interior. Observation by scanning electron microscopy revealed an intricate pattern of irregularly concentric, fine bands and spherules. These had a round, finely banded, globular texture formed by precipitation of ultrafine-grained radiating crystals. The original pore spaces (ie, between spherules, between bands and spherules, or between crystal generations) could be observed as primary porosity. Precipitation and dissolution of these urinary calculi were observed to be spontaneous processes, which can occur simultaneously within an individual calculus. Another prominent feature of the ultrastructure was secondary porosity (spontaneous dissolution) which, in its incipient stages, appeared to be site-selective (ie, some bands appeared to be more susceptible to development of pinpoint porosity). Textures indicative of dissolution were observed not only on the calculus surface, but within the calculus interior as well. Areas that had more advanced stages of dissolution, resulting in increased secondary porosity, also were observed. All 17 samples of the study were found to be composed of calcium carbonate in the form of the mineral calcite, although minor quantities of 2 other polymorphs of calcium carbonate, minerals vaterite and aragonite, also were encountered. Vaterite was observed in 5 of the samples, whereas aragonite was found in 1 sample. Strontium and sulfur were observed as trace elements in 3 of the calculi, whereas magnesium was present in all calculi. Magnesium was observed to substitute for calcium within the calcite crystal lattice in larger quantities than those of strontium or sulfur. Magnesium K alpha X-ray dot maps generated by use of an electron microprobe analyzer indicated that the distribution pattern of magnesium appeared to closely follow layer-by-layer growth of the calculus. Magnesium distribution also appeared to be related to porosity development. In samples where preferential dissolution was observed, the more porous areas had higher magnesium content. Quantitative chemical analyses, using the electron microprobe analyzer, confirmed these observations. Association of the magnesium distribution pattern to the primary growth texture of the calculus indicated that magnesium content of the calculus varied during the formation process. This also indicated that changes in urine chemical analytes may be reflected in composition of the calculi formed.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 7998691 TI - Evaluation of topically administered tissue plasminogen activator for intraocular fibrinolysis in dogs. AB - Fibrin clots were induced in eyes of dogs by injection of autogenous citrated plasma into the anterior chamber. Twenty-four hours after clot formation, one 50 microliters drop of tissue plasminogen activator at a concentration of 5 mg/ml (group 1, n = 7) was administered topically 9 times at 5-minute intervals, or a collagen shield that was hydrated with tissue plasminogen activator at a concentration of 5 mg/ml (group 2, n = 7) was applied. The contralateral eye served as a nontreated control. Serial photographs were taken of the fibrin clots after topical application of tissue plasminogen activator. Computerized morphometric analysis was then used to evaluate changes in cross-sectional surface area of the fibrin clot. There was no significant mean percentage decrease in clot surface area of treated eyes of group-1 dogs or in treated eyes of group-2 dogs. In addition, there was no significant difference in mean percentage decrease in clot surface area between treated eyes of group-1 and group-2 dogs. PMID- 7998692 TI - Biological half-life of aerosolized 99mTc-diethylenetriaminepentaacetate in various lung regions of clinically normal beagles. AB - The biological half-life (TB) of aerosolized 99mTc-diethylenetriaminepentaacetate was determined in 14 lung regions of 18 clinically normal Beagles. Three groups of lung regions or volumes were identified on the basis of significantly (P < 0.05) different TB. Group A (mean +/- SD TB, 82 +/- 21 minutes) included the transversely oriented cranial and caudal nonperihilar regions. Group B (mean +/- SD, 61 +/- 15 minutes) represented all sagittally oriented lung regions and the entire lung field. Group C (mean +/- SD, 49 +/- 11 minutes) included the transversely oriented cranial and caudal perihilar regions. Clearance of 99mTc diethylenetriaminepentaacetate is considered a function of transepithelial transport into the blood, as well as bronchial transport via the mucociliary transport mechanism. PMID- 7998693 TI - Decrease in the alpha 1-proteinase inhibitor Spi3 in equine bronchoalveolar lavage fluid. AB - The alpha 1-proteinase inhibitors of trypsin, Spi1, Spi3A, and Spi3B, in bronchoalveolar lavage fluid (BALF) and serum of horses were separated by electrophoresis, and their proportions were quantified in 12 control horses and 12 with chronic obstructive pulmonary disease (COPD). A significantly lower proportion of Spi3B (P < 0.05) and higher proportion of Spi1 (P < 0.02 to P < 0.01) were detected in BALF, compared with serum, in control and COPD-affected horses and appeared to be attributable to reduced Spi3 activity in BALF. There was no significant difference between the control and COPD groups in this respect, indicating that the decrease in Spi3 may be a physiologic phenomenon. The differences observed may be associated with proteolytic damage to or preferential complex formation by Spi3. PMID- 7998694 TI - Reduction of the prevalence of pseudorabies virus-infected breeding pigs by use of intensive regional vaccination. AB - The influence of an intensive vaccination program on prevalence of pseudorabies virus (PRV)-infected breeding pigs was examined in a region where the disease was enzootic. In a 2-year period, significantly (P < 0.005) greater decrease in the prevalence of PRV-infected breeding pigs was observed in herds participating in the regional vaccination program and in herds outside the trial region that intensified PRV vaccination during the study than in herds that applied routine PRV control measures. In the regional vaccination program, introduction of breeding stock from outside the area was significantly (P < 0.05) associated with higher prevalence of PRV-infected pigs at the end of the study. These results indicate that transmission of PRV can be markedly reduced by use of an accurately applied intensive vaccination program. PMID- 7998695 TI - In vitro susceptibility of equine Salmonella strains to trimethoprim and sulfonamide alone or in combination. AB - The in vitro activity of trimethoprim (TMP) and 9 sulfonamides and their combinations in 6 concentration ratios was tested against 62 Salmonella strains isolated from horses over a 3-year period in the Netherlands, using the agar dilution method. Most of the isolates were S typhimurium strains (n = 52); the others were S heidelberg (n = 3), S hadar (n = 2), S thompson (n = 2), S enteritidis (n = 1), S infantis (n = 1), and S derby (n = 1). The minimal TMP concentration at which 50% of the Salmonella strains were inhibited (MIC50) was 0.12 micrograms/ml. Sulfachlorpyridazine (SCP; MIC50, 16 micrograms/ml), sulfamethoxazole (SMX; MIC50, 32 micrograms/ml), and sulfadiazine (SDZ; MIC50; 32 micrograms/ml) were the most potent of the sulfonamides tested. The antimicrobial effect of the sulfonamides, in combination with TMP (additive, synergistic, or antagonistic), was expressed by the fractional inhibitory concentration (FIC) index. Concentrations of SDZ and SCP with TMP had marked synergism at all tested TMP-to-sulfonamide concentration ratios (1:1 to 1:160; FIC index, 0.10 to 0.50); SMX had synergy with TMP at all ratios, except 1:1 (FIC index, 0.10 to 0.27). Sulfamethazine, sulfamerazine, sulfadoxine (SDX), sulfatroxazole, sulfadimethoxine, and sulfacetamide had MIC50 greater than their breakpoint MIC value and are, therefore, less potent drugs. However, synergy with TMP was found for these less potent sulfonamides at certain concentration ratios, depending on the sulfonamide used. Sixteen Salmonella strains were resistant to TMP, all sulfonamides, and TMP-sulfonamide combinations; 14 of these strains were S typhimurium phage type 200, 1 was S typhimurium phage type 61, and 1 was S typhimurium phage type 10.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7998697 TI - Comparison of cellular and extracellular proteins expressed by various isolates of Mycobacterium paratuberculosis and other mycobacterial species. AB - Protein expression profiles of 10 isolates of Mycobacterium paratuberculosis, M avium 18 (formerly M paratuberculosis 18), and 1 isolate each of M avium serotype 2, M avium serotype 8, and M bovis BCG were examined. Protein expression profiles of M paratuberculosis and M avium were similar. However, two-dimensional gel analysis of [35S]methionine-labeled cellular proteins resolved 4 proteins, with molecular mass of 28,000, 32,000, 32,000, and 42,000 daltons, which were expressed in greater amounts in M paratuberculosis than in M avium. Two proteins, with molecular mass of 43,000 and 60,000 daltons, were identified, which were expressed in greater amounts in M avium than in M paratuberculosis. Immuno (western)-blot analysis, using antiserum from 2 cows clinically infected with M paratuberculosis as the primary antibodies, suggested that the 42,000-dalton protein may be specific for M paratuberculosis. Comparison of protein expression profiles may be useful as a tool for differentiating isolates of M paratuberculosis. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis of [35S]methionine-labeled extracellular proteins revealed variability among the isolates. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis of [35S]methionine-labeled cellular proteins divided the M paratuberculosis isolates into 2 groups on the basis of a difference in the amount of expression of a 28,000-dalton protein. This information may be useful in epidemiologic studies. PMID- 7998696 TI - Temporal characterization of transplacental infection of porcine fetuses with porcine reproductive and respiratory syndrome virus. AB - Pregnant gilts were exposed to porcine reproductive and respiratory syndrome virus (PRRSV) by IV inoculation at or about gestation day 30 (3 gilts), 50 (3 gilts), 70 (3 gilts), or 90 (5 gilts) to investigate the likelihood of transplacental infection with PRRSV at various stages of gestation. At or about 3, 6, and 9 weeks after exposure, gilts were either euthanatized while still pregnant or allowed to farrow. Gilts and pigs were observed for clinical signs of infection, and gilts, pigs, and fetuses were tested for PRRSV and homologous antibody. All gilts were healthy throughout the study, except that farrowing was sometimes difficult and prolonged, and 2 gilts failed to farrow the entire litter. One gilt farrowed on day 111 of gestation; all others farrowed on day 114 or later. Porcine reproductive and respiratory virus was isolated from significantly (chi 2 test, P < 0.01) more fetuses and live and stillborn pigs of the 5 gilts that were infected at 90 or 92 days of gestation than from the fetuses and live and stillborn pigs of the 9 gilts that were infected at 72 or fewer days of gestation (ie, 33 of 44, 75% vs 3 of 78, 4%). After initial infection, PRRSV was isolated from gilts and their pigs for a maximum of 3 weeks and 8 to 11 weeks, respectively. Findings of this study, with regard to the temporal aspects of transplacental infection, may help explain why natural epizootics of PRRSV-induced maternal reproductive failure are often recognized principally as problems of late-term gestation and neonatal survival. PMID- 7998698 TI - Effects of protein, lipid, or carbohydrate supplementation on hepatic lipid accumulation during rapid weight loss in obese cats. AB - Effects of restricted tube-feeding (25% of energy requirements) of protein, lipid, or carbohydrates on body weight loss; hematologic and clinical chemical variables; plasma lipid and amino acid concentrations; nitrogen balance; and hepatic histologic features and lipid concentrations were compared with values in voluntary-fasting cats (control, CON). Twelve obese cats (6.1 +/- 0.1 kg, > 40% above optimal body weight) were randomly assigned to 4 matched treatment groups (n = 3)--protein (PRO), lipid (LIP), carbohydrate (CHO), and CON--and were offered a low-palatability diet for 4 weeks. Cats of the PRO, LIP, and CHO groups were also tube-fed isocaloric amounts (88 kcal of metabolizable energy) of a casein-soybean protein mixture, corn oil, or a dextrin-dextrose mixture, respectively, during the 4 weeks. All cats fasted, rather than eat the low palatability purified diet. Cats of the PRO group lost weight at a lower rate (P < 0.05) than did cats of other groups. After 4 weeks of fasting, serum alkaline phosphatase activities were higher than reference values in all cats of the CON and LIP groups and in 2 cats of the CHO group. At that time, 1 cat of the LIP group had lethargy, hepatomegaly, and hyperbilirubinemia. Total hepatic lipid and triglyceride concentrations increased in all groups during the study, but the increase was significantly (P < 0.05) less in cats of the PRO group, compared with those of the CON and LIP groups, and those of the CHO group, compared with those of the LIP group.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7998700 TI - Antigenic analysis of Dictyocaulus viviparus by use of test-positive bovine sera. AB - An antigen extract of Dictyocaulus viviparus was analyzed by use of sodium dodecyl sulfate-polyacrylamide gel electrophoresis, and the antigen-recognition patterns of serum antibody from cattle not infected, cattle infected with D viviparus, and cattle with unknown history of D viviparus were analyzed by the use of ELISA and western blotting techniques. Cross-reactive antibody-recognition patterns were determined by comparing western blots of D viviparus-positive sera with blots of D viviparus-negative sera obtained from cattle singly infected with Bunostomum phlebotomum, Cooperia oncophora, C punctata, Nematodirus helvetianus, Oesophagostomum radiatum, or Ostertagia ostertagi. Five antigen bands unique to D viviparus were identified, and their frequency of appearance in western blots of sera from verified D viviparus-positive and -negative cattle, and sera from cattle exposed to the parasite, but with unknown D viviparus immune status, were determined. Of the 5 antigens unique to D viviparus, 29- and 19-kd bands had the highest frequencies of reaction (45.9 and 59.0%, respectively) with the test sera. These bands had strong reactivity with sera containing antibodies to D viviparus and did not react with the heterologous sera. We conclude that the 29- and 19-kd antigens may be useful for developing an improved serodiagnostic test for D viviparus infections in cattle. PMID- 7998699 TI - Residual nematocidal effectiveness of ivermectin in cattle. AB - We assessed the duration of ivermectin persistence by measuring posttreatment nematocidal effectiveness; topical and injectable formulations of ivermectin were evaluated. Thirty-five nematode-free calves were randomly allocated to 1 of 5 treatment groups (7 calves/group). The treatment (Trt) group designations were: Trt 1, nonmedicated; Trt 2, injectable ivermectin administered at the rate of 0.2 mg/kg of body weight on day 0; Trt 3, injectable ivermectin administered at the aforementioned rate, but on day 7; Trt 4, topically administered ivermectin at the rate of 0.5 mg/kg on day 0; and Trt 5, topically administered ivermectin at the aforementioned rate, but on day 7. All calves were subsequently given infective larvae of Haemonchus, Cooperia, Trichostrongylus, and Oesophagostomum spp on day 21. One week later, each calf was additionally administered infective larvae of Dictyocaulus and Ostertagia spp. Trial calves were euthanatized on trial days 49 to 52 for nematode quantitation. On the basis of geometric mean comparisons, total nematode burdens were reduced from control group counts by 98.9 and 86.3% for calves treated on days 7 and 0 with injectable formulations, respectively, and 97.2 and 64.7% for calves treated on days 7 and 0 with pour-on formulations, respectively. Trichostrongylus colubriformis infections were most refractory to the persistent activity of ivermectin, with H placei also proving to be persistence limiting. All treatments were easily administered, and adverse behavioral or tissue reactions were not observed. PMID- 7998701 TI - Pharmacokinetics and pharmacodynamics of acepromazine in horses. AB - A specific, sensitive, reverse-phase high-performance liquid chromatographic assay for acepromazine, with analytic sensitivity as low as 5 ng/ml of plasma, and electrochemical detection with an oxidation potential of 0.7 V, was used to study the pharmacokinetics of acepromazine given at a dosage of 0.15 mg/kg of body weight in horses. The relation between effect and pharmacokinetics of the drug was examined. The effects studied included those on blood pressure, pulse, PCV, measures of respiration function, and sedation. Intravenously administered doses led to a biphasic concentration decay pattern with an alpha-phase distribution half-life of < 3 minutes. The beta-phase half-life was in the range of 50 to 150 minutes. The CNS effects peaked at 20 minutes after administration, and the hemodynamic effects peaked at 100 minutes. In all horses, the most sensitive variable was the PCV, which decreased by up to 20% (P < 0.0001). Systolic, diastolic, and mean blood pressures decreased (P < 0.0001); heart rate was unchanged (P > 0.05). Neither blood gas tensions nor blood pH changed noticeably (P > 0.05). In all horses studied, acepromazine had a significant (P < 0.0001) sedative effect, as observed by posture and alertness. None of the observed pharmacodynamic effects correlated well with plasma acepromazine concentration. These effects persisted beyond the time of detectable acepromazine concentration, indicating that they might be caused by active metabolites, or that their timing could result from complex pharmacokinetic compartment influences. PMID- 7998702 TI - Histopathologic evidence of reperfusion injury in the large colon of horses after low-flow ischemia. AB - Effects of low-flow ischemia and reperfusion of the large colon on mucosal architecture were determined in horses. Twenty-four adult horses were randomly allocated to 3 groups: sham-operated (n = 6), 6 hours of ischemia (n = 9), and 3 hours of ischemia and 3 hours of reperfusion (n = 9). Low-flow ischemia was induced in horses of groups 2 and 3 by reducing colonic arterial blood flow to 20% of baseline values. Systemic hemodynamic and metabolic variables were maintained constant and in a normal physiologic range. Full-thickness biopsy specimens were obtained from the left ventral colon for histomorphologic and morphometric examination at baseline and at 30-minute intervals for 6 hours; additional biopsy specimens were collected at 185, 190, and 195 minutes (corresponding to 5-, 10-, and 15-minute periods of reperfusion in group-3 horses). There were no differences among groups at baseline or across time in group-1 horses for any of the histopathologic variables. There were significant (P < 0.05) increases in percentage of surface mucosal disruption, estimated and measured percentage depth of mucosal loss, mucosal hemorrhage, mucosal edema, and cellular debris index during 0 hour to 3 hours, compared with baseline, and from 3 hours to 6 hours, compared with 3 hours in horses of groups 2 and 3. Estimated percentage depth of mucosal loss and cellular debris index were significantly (P < 0.05) greater in group-3 horses, compared with group-2 horses during the interval from 3 to 6 hours. There were trends toward greater percentage of surface mucosal disruption and mucosal edema during the early phase of reperfusion (3 to 4 hours) and greater mucosal hemorrhage, measured percentage depth of mucosal loss, and mucosal interstitial-to-crypt ratio during the late phase (4 to 6 hours) of reperfusion in group-3 horses vs group-2 horses. Reestablishment of colonic arterial blood flow after low-flow ischemia caused greater mucosal injury than did a comparable period of continued ischemia. Thus, reperfusion injury was detected in the large colon of horses after low-flow arterial ischemia. The serial mucosal alterations that developed in the colon were comparable in horses of groups 2 and 3; however, reperfusion exacerbated colonic mucosal injury. PMID- 7998703 TI - Characterization of the hemodynamic and metabolic alterations in the large colon of horses during low-flow ischemia and reperfusion. AB - Effects of low-flow ischemia and reperfusion of the large colon on systemic and colonic hemodynamic and metabolic variables were determined in horses. Twenty four adult horses were randomly allocated to 3 groups: sham-operated (n = 6), 6 hours of ischemia (n = 9), and 3 hours of ischemia and 3 hours of reperfusion (n = 9). Low-flow ischemia was induced in groups 2 and 3 by reducing colonic arterial blood flow to 20% of baseline. Heart rate, arterial blood pressures, cardiac index, pulmonary artery pressure, right atrial pressure, and colonic blood flow were monitored. Arterial, mixed-venous, and colonic venous blood gas and oximetry analyses; PCV; and blood lactate and pyruvate and plasma total protein concentrations were measured. Data were recorded, and blood samples were collected at baseline and at 30-minute intervals for 6 hours; additionally, data were collected at 185, 190, and 195 minutes (corresponding to 5, 10, and 15 minutes of reperfusion in group-3 horses). There were no differences among groups at baseline or across time for any systemic hemodynamic or metabolic variable. Colonic blood flow did not change across time in group-1 horses. Colonic blood flow significantly (P < 0.05) decreased to 20% of baseline at induction of ischemia in horses of groups 2 and 3 and remained significantly decreased throughout the ischemic period in horses of groups 2 (6 hours) and 3 (3 hours). Colonic blood flow significantly (P < 0.05) increased above baseline by 5 minutes of reperfusion in group-3 horses. Colonic oxygen delivery and oxygen consumption, and colonic venous pH, PO2, percentage saturation of hemoglobin, and oxygen content were significantly (P < 0.05) decreased within 30 minutes after induction of ischemia in horses of groups 2 and 3; colonic venous PCO2, colonic oxygen extraction ratio, and lactate and pyruvate concentrations were significantly (P < 0.05) increased by 30 minutes of ischemia. These alterations continued throughout ischemia, but within 5 minutes of reperfusion in group-3 horses, these variables either returned to baseline (pH, PCO2, lactate, pyruvate), significantly (P < 0.05) increased above baseline (PO2, oxygen content, % saturation of hemoglobin), or significantly (P < 0.05) decreased below baseline (colonic oxygen extraction ratio). Colonic oxygen consumption remained decreased during reperfusion in group 3 horses. Colonic mucosal ischemia-reperfusion injury observed in this model of ischemia was associated with local colonic hemodynamic and metabolic alterations in the presence of systemic hemodynamic and metabolic stability.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 7998704 TI - Neutrophil accumulation in the large colon of horses during low-flow ischemia and reperfusion. AB - Histomorphologic/morphometric evaluation, leukocyte scintigraphy, and myeloperoxidase activity were used to determine whether neutrophils accumulate in the large colon of horses during low-flow ischemia and reperfusion. Twenty-four adult horses were assigned to 1 of 3 groups: group 1, sham-operated (n = 6); group 2, 6 hours of ischemia (n = 9); and group 3, 3 hours of ischemia and 3 hours of reperfusion (n = 9). Low-flow ischemia of the large colon was induced in horses of groups 2 and 3 by reducing colonic arterial blood flow to 20% of baseline. Radiolabeled (99mTc) autogenous neutrophils were injected at 175 minutes, which corresponded to 5 minutes prior to reperfusion in group-3 horses. Full-thickness biopsy specimens of the left ventral colon were collected at baseline and at 30-minute intervals for 6 hours; a portion of the biopsy specimen was placed in formalin for histologic examination, and the remainder was used to measure mucosal radioactivity and myeloperoxidase activity. There were no differences in baseline mucosal neutrophil index, mucosal neutrophil numbers, submucosal venular neutrophil numbers, mucosal radioactivity, or mucosal myeloperoxidase activity among groups, or over time in group-1 horses. Neutrophils accumulated in the colonic mucosa during ischemia and further increased at reperfusion, as indicated by neutrophil index (morphology) and mucosal neutrophil numbers (morphometry); mucosal neutrophil index was significantly (P < 0.05) greater in group-3 horses during reperfusion than at the corresponding periods of ischemia in group-2 horses. Neutrophil numbers were significantly (P < 0.05) increased in submucosal venules at 10 minutes of reperfusion in group-3 horses and were significantly (P < 0.05) greater in group 3 than in group-2 horses during the interval from 3 to 6 hours. Mucosal radioactivity significantly (P < 0.05) increased at reperfusion in group-3 horses; there was a trend (P = 0.076) toward greater mucosal radioactivity in group-3, compared with group-2 horses, throughout the 3- to 6-hour interval. There were no differences in mucosal myeloperoxidase activity among or within any of the 3 groups over time. Neutrophils accumulated in the large colon of horses during low-flow ischemia and reperfusion. Neutrophil infiltration was detected by histologic examination and leukocyte scintigraphy, but not by measurement of myeloperoxidase activity. The accumulation of neutrophils during ischemia and the further neutrophil infiltration during reperfusion indicate that neutrophils may contribute to reperfusion injury of the large colon. PMID- 7998705 TI - Atrial and ventricular myocardial blood flows in horses at rest and during exercise. AB - Right atrial, pulmonary artery, pulmonary capillary, pulmonary artery wedge, and systemic blood pressures of strenuously exercising horses increase markedly. As a consequence, myocardial metabolic O2 demand in exercising horses must be high. Experiments were, therefore, carried out on 9 healthy, exercise-conditioned horses (2.5 to 8 years old; 481 +/- 16 kg) to ascertain the regional distribution of myocardial blood supply in the atria and ventricles at rest and during exercise. Blood flow was measured, using 15-micron-diameter radionuclide-labeled microspheres that were injected into the left ventricle while reference blood samples were being withdrawn at a constant rate from the thoracic aorta. Myocardial blood flow was determined at rest and during 2 exercise bouts performed on a high-speed treadmill at 8 and 13 m/s (0% grade). The sequence of exercise bouts was randomized among horses, and a 60-minute rest period was permitted between exercise bouts. There was considerable heterogeneity in the distribution of myocardial perfusion in the atria and the ventricles at rest; the right atrial myocardium received significantly (P < 0.05) less perfusion than did the left atrium, and these values were significantly (P < 0.05) less than those for the respective ventricular myocardium. The right ventricular myocardial blood flow also was significantly less than that in the left ventricle. With exercise, myocardial blood flow in all regions increased progressively with increasing work intensity and marked coronary vasodilation was observed in all cardiac regions. During exercise at 8 or 13 m/s, right and left atrial myocardial blood flows (per unit weight basis) were not different from each other.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7998706 TI - Evaluation of a single-injection method for estimating glomerular filtration rate in dogs with reduced renal function. AB - Two methods for evaluating glomerular filtration rate (GFR), after single i.v. administration of inulin, were assessed in dogs after partial nephrectomy. The first method, determination of plasma clearance of inulin (PCIn), was taken as the quotient of the administered dose of inulin (1,000 mg) divided by the area under the plasma inulin concentration vs time curve. The second estimate of renal function was obtained from the plasma concentration of inulin 75 minutes after i.v. administration of 1,000 mg: C(75). The values for PCIn and C(75) were related (R2 = 0.955, P < 0.0001 and R2 = 0.867, P < 0.0001, respectively) to a previously validated method for measurement of GFR in dogs, urinary clearance of exogenous creatinine (CCr). Results of this study support use of PCIn and C(75) values to estimate GFR in dogs with reduced renal function. In particular, PCIn and C(75) were closely related to CCr in partially nephrectomized dogs with plasma creatinine concentration within the reference range for clinically normal dogs. PMID- 7998707 TI - Evaluation of total serum bile acids concentration and bile acid profiles in healthy cats after oral administration of ursodeoxycholic acid. AB - Ursodeoxycholic acid (UDCA; 10 mg/kg of body weight) was administered orally to 5 healthy cats for 3 months. Signs of illness were not apparent in any cat during treatment with UDCA. Results of monthly CBC, serum biochemical analysis, and urinalysis were unchanged during drug administration. There was a decrease in serum cholesterol concentration in 4 cats. Total postprandial serum bile acids (PPSBA) concentration was significantly (P = 0.0003) increased over total preprandial serum bile acids (PRSBA) concentration at all sample collection periods. The PRSBA and PPSBA concentrations were significantly (P < 0.05) increased at all sample collection periods after administration of UDCA, compared with baseline values. Ursodeoxycholic and tauroursodeoxycholic acids were not detected in serum prior to initiating administration of UDCA. Both bile acids were detected in the serum of all cats 1 and 2 months after UDCA administration and were detected in the serum of 2 cats 3 months after initiating UCDA administration. Hepatic ultrasonographic findings were normal before and after completion of UDCA administration. A mild, focal lymphocytic infiltrate was observed in 3 cats 3 months after initiating UDCA administration. Results of the study indicate that UDCA is absorbed into the systemic circulation of cats after oral administration, undergoes hepatic conjugation, and appears to be safe. PMID- 7998708 TI - Effect of isoflurane on hematologic variables in ferrets. AB - Effects of isoflurane on the CBC in ferrets were studied. There was rapid decrease in all hematologic variables after induction of anesthesia. Percentage reductions in indices of the erythron (hematocrit, RBC count, hemoglobin concentration) exceeded those of plasma protein concentration and WBC count at the first postinduction time point. There was little additional decrease in these variables for the duration of anesthesia. The values had partially recovered to preanesthetic baseline at 45 minutes after anesthesia. Although these alterations appear to be well tolerated in healthy ferrets, care should be exercised when subjecting anemic, geriatric, or debilitated ferrets to isoflurane-induced anesthesia. PMID- 7998709 TI - Acute effects of perineural administration of sodium hyaluronate on palmar digital neurectomy sites in horses. AB - Biaxial palmar digital neurectomy of all limbs was performed on 6 mixed-breed castrated adult male horses, using a standard guillotine method. Using a Teflon catheter, 20 mg (2 ml) of sodium hyaluronate (group 1), 2 ml of phosphate buffered saline solution (group 2), or catheter placement with no infusion (group 3) was applied to 4 (group 1) or 2 (groups 2 and 3) of 8 incisions/horse. Treatments were administered after closure of the neurectomy incision, and the catheter was removed. Horses were evaluated daily for 1 week, then weekly over a 9-week period for evidence of lameness, swelling, and ultrasonographic changes. On week 9, horses were euthanatized and neurectomy sites were removed en bloc for histologic evaluation of axonal regrowth, inflammation, and fibrosis. Neither lameness nor sign of painful neuroma was observed clinically in any of the horses. Neurectomy eliminated cutaneous heel sensation in all limbs for the duration of the study. Swelling was evident at all neurectomy sites. There were no significant differences between treatment sites for measurement of pastern circumference or ultrasonographic evaluation of incisional swelling. Foci of ultrasonographic hyperechogenicity increased over time, but there was no significant difference in hyperechogenicity between treatment groups. Histologic evidence of neuroma formation was observed at all sites. Morphometric assessment of neuroma cross-sectional areas revealed no significant difference between the groups, as did subjective histologic assessment of neuroma density and fibrous tissue content.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7998710 TI - [Spirit and madness. The Maison Blanche at Montmartre]. AB - Dr Prost's psychiatric clinic was managed by the doctors Blanche senior and junior (Esprit and Emile), then by doctors Meuriot senior and junior during more than one century from Napoleon's First Empire until the end of the first world war (1914-1918). This clinic acquired a sound reputation and celebrity thanks to the use of new psychiatric methods and a practice open to all artists and literary elite at that time, with whom the successive owners kept friendly relationships. PMID- 7998711 TI - [Language and psychiatry]. AB - Language is intimately linked with knowledge. In psychiatry it is initially focused upon the patient and proves to be a natural language. When the studies are extended to the social environment, the use of statistics and more general properties orientates it towards logico-mathematical abstractions. Finally in order to respect the singular and universal aspect of the mentally sick person, the logical operations are integrated within the discourse. It is the case especially for the systemal method, for interdisciplinary studies and retroactive study of the observer's own ways of thinking. In this way it is eventually possible to extract organic laws. In conclusion psychiatric language proves to be an instrument of communication for the person, within himself and with the outer world, taking the shape of a wider and wider spiral, better and better expressing phenomena with singular et universal meanings. PMID- 7998712 TI - [Method of formalization and transfer of emergency psychiatric expertise]. AB - The different steps of the project and mainly the knowledge acquisition process in the field of emergency medicine meant for French Navy warships are described. We focus on Psychiatry and more especially on the subset of pathologies that may lead to suicide. A knowledge base dealing with these questions is connected to a hypothetico-deductive automaton that is able to simulate physician's reasoning. From initial symptoms gathered by the user, the system dynamically focuses the interferences in order to suggest an adequate policy, even under relative uncertainty, taking into account the logistic and operational conditions on board. The final goal is to integrate other emergency medicine fields into the expert system shell. PMID- 7998713 TI - [The death of Helene Althusser: a case of altruistic homicide reported by the melancholic person]. AB - Authors suggest to read carefully the text written by Louis Althusser concerning the murder of his wife, Helene. In place of hypothetical psychopathological elaborations they propose to take into account the narration of his personal story, and his illness leading to a delusional and confusional depression. The precision in the written report by Althusser on his painful manic depression demonstrates that there is no place for hypothesis too different from an ordinary reality. PMID- 7998714 TI - [Hypophyseal adenomas. Psychiatric evaluation before and after surgical excision]. PMID- 7998716 TI - [The consumption of "crack" in Paris in 1993. Epidemiological and ethnographic data]. AB - In France, trends of cocaine use have been increasing regularly since 1980. "Crack" has been noticed for the first time in 1987. "Crack" is a smokable form of cocaine which is easily processed starting from cocaine hydrochloride. In 1993 a very important spread of "crack" use has been observed by our street team. It is very clear that "crack" use has been underestimated in Paris. The medical and social management of addicts could be severely affected by this new phenomenon. PMID- 7998715 TI - [Benzodiazepine drug ingestion and evaluation of after care]. AB - Voluntary drug ingestion with benzodiazepine represent today the most frequent method of attempt of autolysis. One must note the difficulties the doctor may find in front such problems to judge the reliability of interviews made in such difficult conditions. Residual disturbances of superior functions, more precisely of vigilance during the period with follow the suicidal action must not be overlooked. Thanks to a clinical scale easily used the residual disturbances have been put in evidence on a sample of 20 subjects who had been admitted with this aim in view in a university ward specialized in psychiatric emergencies. The possibility of continuity within middle range care must allow an improvement of minimum care of such pathologies. PMID- 7998717 TI - [The wounded identity. The rediscovered name]. PMID- 7998718 TI - [Chronic crisis or recurrence of emergencies]. AB - The authors have studied the characteristics of a group of chronic crisis patients among those who were treated in the psychiatric emergency unit of Rene Dubos General Hospital (Pontoise, France). The population was defined as patients who visited the unit four times or more during one year (from 01/07/1991 to 30/06/1992). These 70 patients represent 4.3% of the total number of individuals who were treated in the emergency setting during the same year. 1568 patients were treated as out patients, or hospitalized for a short time, not exceeding 48 hours). Two sub groups can be distinguished. The first one is composed of patients who repeat their visits during a total period of less than 3 months. The second sub group is composed of repeaters who are seen regularly but for a longer period of time. The socio demographic and clinical characteristics (DSM-III R) of the two sub groups are discussed. PMID- 7998719 TI - Beyond the Crisis: Preserving the Capacity for Excellence in Health Care and Medical Science. New York City, New York, February 14-15, 1994. PMID- 7998720 TI - Fusing excellence to reform. PMID- 7998721 TI - Impact of health care reform on research innovativeness. PMID- 7998723 TI - Spending to save: financial reform for the medicine of the future. PMID- 7998724 TI - Health care reform: impact on R&D and innovation in the biotechnology industry. PMID- 7998722 TI - The contribution of pharmaceutical companies: what's at stake for America. Executive summary from a report prepared by the Boston Consulting Group. PMID- 7998725 TI - The significance of health care reform for research, innovations, and academic medicine. PMID- 7998726 TI - Quality versus excellence: introductory remarks. PMID- 7998727 TI - Quality and excellence--essential and inseparable. PMID- 7998728 TI - Measuring quality: where are we? Where are we going? And how will we know when we get there? PMID- 7998729 TI - Promoting excellence in health care: a legal perspective. PMID- 7998730 TI - Clinical excellence and research: one and indivisible. PMID- 7998731 TI - The politics of quality versus excellence. PMID- 7998732 TI - Preserving the capacity for excellence: valid measures of quality. PMID- 7998733 TI - The reform forecast for society's health care commons: heavy fog and hazardous driving conditions. PMID- 7998734 TI - Geriatrics and health care reform: opportunities in managed care for preserving excellence in the care of the elderly. PMID- 7998735 TI - Defining social choices and distributing social resources on the health care commons. PMID- 7998736 TI - It's the medicine, stupid. PMID- 7998737 TI - Art, science, and the doctor-patient relationship. PMID- 7998738 TI - The doctor-patient relationship. PMID- 7998739 TI - The doctor-patient relationship: quantification of the interaction. PMID- 7998740 TI - Excellence in clinical subspecialties. PMID- 7998741 TI - In defense of health care: preserving the capacity for excellence. PMID- 7998742 TI - Doctor-patient and doctor-patient-society relationships after health care reform. PMID- 7998743 TI - Medical education: reexamining the roles. PMID- 7998744 TI - The physician as health agent. PMID- 7998745 TI - The generalist physician. PMID- 7998746 TI - Three threats to the capacity for excellence in medicine. PMID- 7998747 TI - Some potential impacts of health care reform on medical education. PMID- 7998748 TI - The states as health reform laboratories. PMID- 7998749 TI - Research and innovation: introduction. PMID- 7998750 TI - The state of the art of ultrasonography in the head and neck. AB - When considering patient comfort, length of testing, availability, the increased diagnostic capabilities and relative cost, we believe that ultrasonography is an important addition to the diagnostic tests currently used in otolaryngology. It is a noninvasive method with high sensitivity. When one includes the techniques of ultrasound-guided fine-needle aspiration, cutting biopsy and colour-coded duplex sonography, the specificity is further augmented and is superbly suited for demonstrating, detecting and excluding pathologies in the head and neck region. It will increase the accuracy of preoperative staging of patients with head and neck squamous cell cancer. It is even possible that it may change the indications for therapeutic and elective neck treatment. In addition it is valuable during the follow-up of patients treated with radiation or/and chemotherapy. In many situations, ultrasonography is superior to CT or MRI because it is a dynamic imaging technique with the possibility of simultaneous palpation of the lesion. It does not force the surgeon to reconstruct anatomy from computer generated slices which leave gaps that may miss disease and it can detect major vessel invasion by tumour. PMID- 7998751 TI - [Otosclerosis: study of the postoperative course of hearing during the first 5 years and research of some prognostic factors. Apropos of a series of 67 cases]. AB - Post-operative air conduction and bone conduction thresholds at 3 months, 1 year and 5 years after stapedectomy or stapedotomy in 67 patients were studied. Bone conduction thresholds improved in the first year postoperatively, then decreased progressively, less than in the non-operated ear but more than in a normal population. The air-bone gap was closed in 75% of the patients. The air-bone gap stayed at the same level during the studied period. Air conduction and bone conduction thresholds are better in the stapedotomy group than in the stapedectomy group only in the 4000 Hz frequency, and are similar for both groups in the 500-2000 Hz range. PMID- 7998752 TI - [Functional endoscopic surgery of sinusal mucocele]. AB - The treatment of paranasal sinus mucoceles must assure complete removal and prevention of recurrence. In order to clarify the precise indications for endoscopic management, a retrospective study was undertaken on 16 patients with paranasal sinus mucoceles treated by this method. All of the patients underwent endoscopic exploration with or without an associated bicoronal approach. The follow-up period varied between 3 months and 46 months with a mean of 24. The results were considered satisfactory if the patient's symptoms disappeared and follow-up endoscopy revealed persistence of sinus permeability. Functional endoscopic surgery can be considered as an alternative method in treatment of sinus mucoceles. Only mucoceles confined to the lateral wall of the frontal sinus, and the extended mucoceles, seem to be an out of the way place to endoscopic sinus surgery alone. In these cases, the access has to be completed by an external approach. Concerning adequate recanalization of the nasofrontal duct, results seem encouraging, however a long-term follow-up is necessary to obtain an accurate assessment of the results. PMID- 7998753 TI - [Tympanoplasty using chondro-perichondral graft. Indications, techniques and results. Apropos of a series of 127 cases]. AB - In an attempt to avoid recurrence, the authors have used chondro-perichondral grafts for more than 10 years for tympanoplasty of retraction pouches. Early results were published in 1987. This new retrospective series of 127 tympanoplasties, performed from 1987 to 1991 reports the anatomic and functional results obtained and the technical modalities used. After a mean follow-up of 18 months, the results appear encouraging. Indications of this chondro-perichondral graft have been widened to cases of unsuccessful first intention myringoplasty and to certain cases of progressive perforations occurring in a setting of inflammation or tubal dysfunction. The results must be confirmed on the basis of long term outcomes. PMID- 7998754 TI - [Technique of intraoperative treatment of a retro-mandibular defect after parotidectomy. Use of a blot clot]. AB - As noticed in our experience, cosmetic results, after total parotidectomy, were better if the patient presented an hematoma. The author got the idea to fill the retro-mandibular defect with a clot. The technique is presented in detail. Fifty four patients had a total parotidectomy between January 1992 and May 1993. A clot was used in 39 of these 54 cases. Were excluded malignant tumors, superficial parotidectomies or the presence of a general pathology (diabetes, cirrhosis). The result was excellent in 31 cases even if a local treatment was necessary due to a secondary hematoma. There was no infectious complication. The follow-up of this series is insufficient, but by analogy with spontaneous hematoma, the results should be persistent. This technique is simple, does not increased the time of the surgical procedure and does not induced injury on any donor site. PMID- 7998755 TI - [Giant cementifying fibroma of the maxillary sinus. Apropos of a case]. AB - The case of a patient presenting with a gigantiform fibrous cementoma of the maxillary sinus is described. The diagnostic, the treatment and the histologic classification of the cementifying tumours is reviewed in light of the present literature. PMID- 7998756 TI - [Current data on the antimicrobial spectrum of fusafungin]. PMID- 7998757 TI - [Sudden isolated cochlear deterioration in children]. AB - Within a general study on the long-term outcome of tonal auditive thresholds in children, the authors analyzed 26 cases of sudden onset cochlear deterioration (unilateral or bilateral deficiency without former pathology, or sudden worsening of a known perception loss). The patients were hospitalized and followed the standard treatment course for sudden hearing loss. The characteristics of the former hearing deficiency, the original causes of the deafness or the sudden deterioration, and the short, medium and long-term audiometric thresholds were studied to determine possible prognostic factors. Sudden deafness, fluctuating hearing loss, progressive hearing loss, sudden cochlear deteriorations and the nosologic situation do not appear to have much signification in this poorly defined field of perception deficiency in children. Certain terminologies or classifications would appear simply to hide our ignorance of the true mechanisms underlying these problems. PMID- 7998758 TI - [Lipoproteins containing apolipoprotein A-I and reverse transport of cholesterol]. AB - The antiatherogenic HDLs are heterogeneous in terms both of hydrated density and of lipoprotein composition. The LpA-I and LpA-I: A-II particles seem to be different from a metabolic point of view, and LpA-I and LpA-IV are apparently the only ones involved in the antiatherogenic action of HDLs. Alcohol consumption causes an increase in LpA-I: A-II, but not in LpA-I. Specific HDL binding sites have been demonstrated in various tissues, including steroidogenic tissues, liver cells and peripheral cells. Apolipoproteins A-I, A-IV and A-II are possible ligands. After binding to the uptake site, HDLs allow cholesterol supply to the cells, on one hand, and the removal of cholesterol for "reverse cholesterol transport" from peripheral tissues to the liver on the other hand. In addition, the interaction of the various HDL subfractions can cause different metabolic effects: cholesterol efflux from the adipocytes of cholesterol-laden mice is influenced by the uptake of LpA-I and LpA-IV on receptors, while apolipoproteins A-II are antagonists for this effect. PMID- 7998759 TI - [Plasma fractionation. Progress, problems and perspectives]. AB - In the last few years, plasma fractionation has been subjected to major technological changes which have contributed to improve the viral safety and overall purity of plasma derivatives. New viral inactivation treatments, primarily solvent-detergent and pasteurization, have been introduced in the manufacturing processes of plasma derivatives to ensure the inactivation of major plasma-borne viruses, including HIV and hepatitis B and C viruses. Concurrently, new highly purified products obtained by chromatographic methods (mainly ion exchange and/or immunopurification) have been developed in the last five years and have replaced former preparations, providing a significantly higher safety level in terms of purity and viral risks. For an example, the new generation of Factor VIII and Factor IX concentrates (to treat hemophilia A and hemophilia B, respectively), which have been introduced in the last five years, are purified over 10,000- to 20,000-fold from plasma, as compared to only 50- to 100-fold for the former products. Similarly, new, standardized, clotting factor or protease inhibitor concentrates have been made available, thus permitting to carry out selective hemotherapy of specific diseases. Examples include the development of von Willebrand factor, factor XI, protein C, or alpha 1-antitrypsin concentrates for the substitutive therapy of congenital or acquired deficiencies. In addition, the concept of good manufacturing practices has been implemented, whereas carefully controlled, validated processes are contributing to the consistency in the quality of those products. Current major problems in plasma fractionation relate to the potential occurrence of new pathogenic agents that could resist present viral inactivation treatments and to the potential effect of given purification technologies on the development of immunogenic properties of proteins. Current trends indicate that significant progress in viral safety of plasma derivatives (for example through the introduction of new concept such as viral filtration) are to be expected very soon. Further research in this very important field is mandatory as plasma should remain the starting material of important therapeutic products in the coming years. PMID- 7998760 TI - [Studies of in vitro and in vivo toxicity of dyes used in affinity chromatography]. AB - Some reactive textile dyes are used for years as biomimetic ligands in protein purification. The reluctance to use these performant systems in large scale for therapeutically applicable proteins is related with the possible dye leakage and consequently with problems of contamination. Therefore, toxicology data are necessary to quantify the level of danger in association with sensitive assays. This study deals with a series of in vitro toxicity studies with eucaryotic cells (growth, polyploidia, ...) as well as with procaryotic cells (E. coli) for genotoxic studies. Both approaches demonstrated a total absence of toxicity for all ranges of concentrations investigated for Reactive Blue 2, Reactive Red 120 and their derivatives. Additional experiments done in vivo by the administration of dye solutions to a series of mice confirmed the non toxic character of these dyes in vitro. PMID- 7998761 TI - [Hydromineral composition and phytochemical triage on Crithmum maritimum L. (Apiaceae)]. AB - The authors studied the hydromineral composition of Crithmum maritimum L. (Apiaceae). In the respects, the sorted out the chemical components of the plant, thus pointing out the presence of flavonoids, of quaternary ammoniums, of coumarins and of gums. PMID- 7998762 TI - [Determination of psoralens by gas chromatography]. AB - A gas chromatography capillary column determination of a mixture of psoralens is proposed. The validation of quantitative analysis is detailed and used for the evaluation of psoralens extraction from pharmaceuticals. Moreover stability in acidic or basic media is studied by LC/MS as well as the proposed gas chromatographic methods. A gas chromatography capillary column determination of a mixture of psoralens is proposed. PMID- 7998763 TI - [Paul Rossignol (1923-1994)]. PMID- 7998764 TI - Polymerase chain reaction and the diagnosis of viral central nervous system diseases. PMID- 7998765 TI - Oxygen utilization and delivery in metabolic myopathies. PMID- 7998766 TI - Trinucleotide repeat expansion in neurological disease. AB - Expansion of trinucleotide repeats is now recognized as a major cause of neurological disease. At least seven disorders result from trinucleotide repeat expansion: X-linked spinal and bulbar muscular atrophy (SBMA), two fragile X syndromes of mental retardation (FRAXA and FRAXE), myotonic dystrophy, Huntington's disease, spinocerebellar ataxia type 1 (SCA1), and dentatorubral pallidoluysian atrophy (DRPLA). The expanded trinucleotide repeats are unstable, and the phenomenon of anticipation, i.e., worsening of disease phenotype over successive generations, correlates with increasing expansion size. In this review, we compare the clinical and molecular features of the trinucleotide repeat diseases, which may be classified into two types. Fragile X and myotonic dystrophy are multisystem disorders usually associated with large expansions of untranslated repeats, while the four neurodegenerative disorders, SBMA, Huntington's disease, SCA1, and DRPLA, are caused by smaller expansions of CAG repeats within the protein coding portion of the gene. CAG repeats encode polyglutamine tracts. Polyglutamine tract expansion thus appears to be a common mechanism of inherited neurodegenerative disease. Although polyglutamine tract lengthening presumably has a toxic gain of function effect in the CAG trinucleotide repeat disorders, the basis of this neuronal toxicity remains unknown. PMID- 7998767 TI - Herpes simplex virus genomes in human nervous system tissue analyzed by polymerase chain reaction. AB - Herpes simplex virus (HSV) is known to establish latency in human trigeminal ganglia. It has been speculated that the virus might also be present in latent fashion in normal human brain, where it might be responsible for conditions such as herpes simplex encephalitis, and less plausibly as a cause for multiple sclerosis or Alzheimer's disease. To test the possibility that HSV exists in normal human brain, we utilized the polymerase chain reaction to assess the frequency and distribution of HSV genomes in the nervous system tissues of patients dying of nonneurological causes. Nine samples were obtained in a systematic fashion from olfactory bulb, gyrus rectus, hippocampus amygdala, calcarine cortex, pons, medulla, cerebellum, and trigeminal ganglia from each of 40 individuals dying of nonneurological disease. HSV genomes were sought in each sample using primers from four regions of the HSV genome. The primers were capable of detecting HSV genomic sequences from as little as 10 fg of DNA. HSV genomic sequences were identified in 26 (65%) of 40 samples of trigeminal ganglia. From 30 patients seropositive to HSV, sequences were amplified from 23 (77%). HSV genomic sequences could be amplified and detected in 14 (35%) of 40 brains. The positive areas included medulla, olfactory bulbs, pons, gyrus rectus, amygdala, and hippocampus. The study has confirmed the previous demonstration of latent HSV in trigeminal ganglia in normal humans. The frequency of latent HSV in trigeminal ganglia is in general agreement with results obtained by explanation of ganglia.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7998768 TI - An oxidative defect in metabolic myopathies: diagnosis by noninvasive tissue oximetry. AB - Metabolic myopathies due to a variety of enzymatic deficiencies are well recognized. The dynamics of oxygen delivery and utilization during exercise have not been observed previously in these disorders. We used a noninvasive optical technique to measure oxygen consumption in the exercising limb in normal subjects and patients with metabolic myopathies. We measured near-infrared spectra of hemoglobin in the gastrocnemius muscle during treadmill exercise in 10 normal subjects, 1 patient with cytochrome c oxidase deficiency, 2 patients with myophosphorylase deficiency, 3 patients with phosphofructokinase deficiency, and 2 patients with carnitine palmityl transferase deficiency. All normal subjects demonstrated a sustained deoxygenation during exercise, indicating an efficient utilization of delivered oxygen. The patient with cytochrome c oxidase deficiency demonstrated consistent oxygenation during exercise, indicating an underutilization of delivered oxygen. In the patients with myophosphorylase or phosphofructokinase deficiency, abnormal oxygenation during exercise indicated an oxidative defect due to a lack of pyruvate production. In the patients with myophosphorylase deficiency, changes in oxidation coincident with glucose utilization and "the second wind phenomenon" were observed. Patients with carnitine palmityl transferase deficiency demonstrated a normal deoxygenation during exercise. Noninvasive tissue oximetry during exercise demonstrates specific abnormalities in a variety of metabolic myopathies, indicating abnormal oxygen utilization, and will be a useful addition to the clinical investigation of exercise intolerance. PMID- 7998769 TI - A plasma exchange versus immune globulin infusion trial in chronic inflammatory demyelinating polyradiculoneuropathy. AB - Chronic inflammatory demyelinating polyradiculoneuropathy is a paralytic syndrome, causing considerable disability and even death. In controlled clinical trials, plasma exchange prevented or ameliorated neurological deficits, but the efficacy of immune globulin infusion remains unproved. Also unknown is whether immune globulin infusion is as effective, or more effective, than plasma exchange and what dosages and frequencies are best. In this observer-blinded study, using some objective end points not subject to bias (e.g., summated compound muscle action potential), 20 patients with progressive or static polyneuropathy were randomly assigned to receive either of the two treatments for 6 weeks, followed by a washout period, and then were assigned to receive the other treatment. Plasma exchange (twice a week for 3 weeks then once a week for 3 weeks) and immune globulin infusion (0.4 gm/kg once a week for 3 weeks, then 0.2 gm/kg once a week for the next 3 weeks) were used. End points assessed before and after treatment schedules were neurological disability score; muscle weakness of the neurological disability score; summated compound muscle action potentials of ulnar, median, and peroneal nerves; summated sensory nerve action potentials of ulnar and sural nerves; and vibratory detection threshold of the great toe using CASE IV. Observers were masked as to treatment used. Of 20 patients, 13 received both treatments whereas 4 did not worsen sufficiently to receive the second treatment--1 patient left the study during and 2 after the first treatment to receive unscheduled treatment elsewhere.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7998770 TI - The role of calcium-binding proteins in selective motoneuron vulnerability in amyotrophic lateral sclerosis. AB - The factors contributing to selective motoneuron loss in amyotrophic lateral sclerosis (ALS) remain undefined. To investigate whether calcium-binding proteins contribute to selective motoneuron vulnerability in ALS, we compared calbindin D28K and parvalbumin immunoreactivity in motoneuron populations in human ALS, and in a ventral spinal cord hybrid cell line selectively vulnerable to the cytotoxic effects of ALS IgG. In human autopsy specimens, immunoreactive calbindin-D28k and parvalbumin were absent in motoneuron populations lost early in ALS (i.e., cortical and spinal motoneurons, lower cranial nerve motoneurons), while motoneurons damaged late or infrequently in the disease (i.e., Onuf's nucleus motoneurons, oculomotor, trochlear, and abducens nerve neurons) expressed markedly higher levels of immunoreactive calbindin-D28K and/or parvalbumin. Motoneuron-neuroblastoma VSC 4.1 hybrid cells lost immunoreactive calbindin-D28k and parvalbumin following dibutyryl-cyclic AMP-induced differentiation and were killed by IgG from ALS patients. Undifferentiated calbindin/parvalbumin-reactive VSC 4.1 cells were not killed, nor were other cell lines expressing high levels of calbindin-D28K and parvalbumin immunoreactivity (substantia nigra neuroblastoma hybrid cells and N18TG2 neuroblastoma parent cells). These studies suggest that decreased calbindin-D28K and parvalbumin immunoreactivity may help explain the selective vulnerability of motoneurons in ALS. PMID- 7998771 TI - Childhood Guillain-Barre syndrome in Paraguay, 1990 to 1991. AB - During 1990 to 1991, through a national surveillance program for poliomyelitis, the Paraguayan Ministry of Health received reports of 50 children with incident acute flaccid paralysis (< 15 years old). On the basis of established criteria, 37 were diagnosed with Guillain-Barre syndrome. The average annual incidence rate for 1990 to 1991 was 1.1/100,000 children. The clinical course was more benign than reported in other pediatric series. There were low rates of hospitalization (57%), respiratory compromise (8%), and intubation (5%). The overall severity, however, was similar to that described in previous reports, with a 3% case fatality rate and an 81% total recovery rate at 12 months. Seventy-six percent of patients had symptom onset during January to April, the warmest months of the year. Thirty percent of patients had definite or possible exposure to organophosphate pesticides, and the peak use coincides with the peak incidence of Guillain-Barre syndrome. There was no correlation between occurrence of Guillain Barre syndrome and prior immunization. PMID- 7998772 TI - Evidence for hypoxia-induced, programmed cell death of cultured neurons. AB - Apoptosis, a form of cell death ("programmed" cell death) in which the nucleus and cytoplasm shrink and often fragment, serves to eliminate excessive or unwanted cells during remodeling of embryonic tissues, during organ involution, and in tumor regression. In acute pathological states, such as ischemia, the cells tend to swell and lyse--a process called necrosis. We hypothesize that the delayed neural death clinically associated with hypoxia may, in part, represent apoptosis. A tissue culture model of 24 hours of hypoxia was employed using sympathetic neurons. Pretreatment with an endonuclease inhibitor (aurintricarboxylic acid) decreased cell death by 53%, depolarizing conditions (55 mM potassium chloride) decreased cell death by 33%, and an RNA synthesis inhibitor (actinomycin D) by 26% (all have been shown to prevent apoptosis). Pretreatment with antisense c-myc had no effect. Fluorescent staining with propidium iodide (a DNA marker) demonstrated chromatin condensation and agarose gel electrophoresis demonstrated a DNA "ladder." These data suggest that apoptosis may play a role in hypoxic cell death and that in this paradigm, expression of c-myc is unnecessary. This would suggest a new approach to our understanding of hypoxia and open new strategies to lessen neuronal damage secondary to this process. PMID- 7998773 TI - Manganese intoxication and chronic liver failure. AB - Manganese intoxication and chronic liver failure are associated with strikingly similar clinical, imaging, and pathological abnormalities. As manganese is primarily cleared by the liver, inadequate elimination of manganese absorbed from the normal diet may lead to manganese overload in patients with liver disease. We report a significant elevation of blood manganese concentration in 3 patients with biopsy-proved hepatic cirrhosis who exhibited neurological dysfunction and characteristic abnormal signal hyperintensity in the globi pallidi and substantia nigra on T1-weighted magnetic resonance imaging. We speculate that manganese accumulation in the brain accounts for the magnetic resonance imaging abnormalities and contributes to neurological dysfunction in patients with liver disease. PMID- 7998774 TI - Complex I, iron, and ferritin in Parkinson's disease substantia nigra. AB - Elevated iron levels, enhanced oxidative damage, and complex I deficiency have been identified in the substantia nigra of Parkinson's disease patients. To understand the interrelationship of these abnormalities, we analyzed iron levels, ferritin levels, and complex I activity in the substantia nigra of patients with Parkinson's disease. Total iron levels were increased significantly, ferritin levels were unchanged, and complex I activities were decreased significantly in the substantia nigra samples. The failure of ferritin levels to increase with elevated iron concentrations suggests that the amount of reactive iron may increase in the substantia nigra of Parkinson's disease patients. There was no correlation between the iron levels and complex I activity or the iron-ferritin ratio and complex I activity in the substantia nigra samples. PMID- 7998776 TI - Predictive value of apolipoprotein E genotyping in Alzheimer's disease: results of an autopsy series and an analysis of several combined studies. AB - Apoliprotein E (apoE) is associated with Alzheimer's neurofibrillary tangles and beta-amyloid protein in senile plaques. Recent studies have shown an increased frequency of the epsilon 4 allele of the apoE gene in familial and sporadic cases of Alzheimer's disease (AD). In the present case control study, we have determined the apoE genotype by allele-specific extension of 113 postmortem cases of sporadic AD and 77 control brains shown to be free of AD neuropathological features and then calculated the frequency of the various allelic forms of apoE (epsilon 2, epsilon 3, epsilon 4). The odds ratio associating epsilon 4 with AD was 15.5 (95% confidence interval [CI] 6.2-38.5), and the population attributable risk was 0.53. We have also combined the results of our study and several others to calculate these same parameters in a larger population (570 controls and 961 AD subjects); the odds ratio for this larger group was 6.2 (95% CI 4.9-7.8) and the population attributable risk was 0.57. These results further substantiate and strengthen the association between the epsilon 4 allele of apoE gene and AD. We have also used these results to investigate the usefulness of the determination of epsilon 4 carrier status in the diagnosis of AD. PMID- 7998777 TI - Immunological and pathological study of anti-Ri-associated encephalopathy. AB - A patient with high titers of the anti-Ri antibody died 3 years after a progressive course with ataxia, opsoclonus, dementia, and peripheral neuropathy. At autopsy, no tumor was found. The nervous system exhibited severe Purkinje cell loss and contained perivascular and interstitial inflammatory infiltrates, particularly involving the brainstem. B and CD4 cells predominated in the perivascular spaces and CD8 cells in the interstitial infiltrates. Complement reactivity and natural killer cells were present and predominated in areas with more intense inflammatory infiltrates. Deposits of IgG were detected in the cytoplasm and nuclei of some neurons, particularly those in the brainstem tegmentum. The proportion of anti-Ri IgG in the total IgG extracted from various areas of the brain, serum, and cerebrospinal fluid was determined by quantitative western blot analysis. Anti-Ri reactivity was identified in immunoblots of all regions of the brain, but it predominated in basis pontis and dorsal mesencephalon. Our findings support the hypothesis of an autoimmune basis for the disorder and suggest that an antibody-mediated mechanism may play a role in its pathogenesis. PMID- 7998775 TI - Coenzyme Q10 and nicotinamide block striatal lesions produced by the mitochondrial toxin malonate. AB - A potential mechanism of neuronal injury in neurodegenerative diseases is a defect in energy metabolism that may lead to slow excitotoxic neuronal death. Consistent with this possibility, we showed that specific inhibitors of the electron transport chain produce excitotoxic lesions in vivo. In the present study we examined whether agents that improve energy metabolism can block lesions produced by the mitochondrial toxin malonate. Striatal lesions produced by the complex II inhibitor malonate were blocked in a dose-dependent manner by oral pretreatment with coenzyme Q10. Administration of nicotinamide by Alzet pump for 1 week attenuated malonate-induced lesions, but riboflavin had no effect. Administration of nicotinamide intraperitoneally just prior to and following induction of the lesions produced dose-dependent neuroprotection. A combination of coenzyme Q10 with nicotinamide was more effective than either compound alone, as shown by both lesion size and magnetic resonance imaging in vivo. Both coenzyme Q10 and nicotinamide blocked adenosine triphosphate depletions and lactate increases. These results confirm that mitochondrial toxins produce striatal excitotoxic lesions by a mechanism involving energy depletion in vivo. Furthermore, they suggest novel neuroprotective strategies that may be useful in the treatment of both mitochondrial encephalopathies and neurodegenerative diseases. PMID- 7998778 TI - Amyloid beta protein levels in cerebrospinal fluid are elevated in early-onset Alzheimer's disease. AB - The 4-kd amyloid beta protein (A beta) deposited as amyloid in Alzheimer's disease (AD) is produced and released by normal proteolytic processing of the amyloid beta protein precursor (beta APP) and is readily detected in cerebrospinal fluid (CSF). Here, we present the levels of A beta in CSF from a total of 95 subjects, including 38 patients with AD, 14 with early-onset AD and 24 with late-onset AD, 25 normal control subjects, and 32 patients with other neurological diseases. The level of A beta decreased with normal aging, and there was a significant elevation in the level of A beta in the CSF of early-onset AD patients (4.14 +/- 1.37 pmol/ml, p < 0.01). Neither Mini-Mental State nor Functional Assessment Staging were correlated with the amount of A beta in the CSF. The A beta/secreted form of beta APP ratio was elevated, but the level of alpha 1-antichymotrypsin in the CSF did not correlate with the level of CSF A beta in early-onset AD patients. Thus, the level of A beta in the CSF is elevated in early-onset AD patients and is suggested to be correlated with the pathology in the brain that characterizes AD. PMID- 7998779 TI - Phenotypic heterogeneity of an adult form of adrenoleukodystrophy in monozygotic twins. AB - We describe genetically proven monozygotic twins with the adult form of adrenoleukodystrophy with significant phenotypic heterogeneity. Myeloneuropathy was common to both patients, but cognitive impairment and affective symptoms with extensive demyelination in the brain were prominent in the older twin, while adrenal insufficiency was predominant in the younger twin. The younger twin, however, exhibited affective symptoms similar to those displayed by his elder twin 10 years later. These findings suggest that nongenetic factors are important in determining the phenotypic variation of adrenoleukodystrophy gene. PMID- 7998780 TI - Pelizaeus-Merzbacher disease presenting as spinal muscular atrophy: clinical and molecular studies. AB - Two brothers with profound neonatal hypotonia and hyporeflexia and electrodiagnostic testing consistent with lower motor neuron pathology were found to have a leukodystrophy. Using single-strand conformational polymorphism analysis and direct sequencing, a mutation within exon 3 of the gene encoding proteolipid protein (Gly73Arg substitution) was previously detected in both brothers and their mother, establishing the diagnosis of Pelizaeus-Merzbacher disease. Despite reported sparing of the peripheral nervous system in Pelizaeus Merzbacher disease, we suggest that proteolipid protein gene products may influence the development of anterior horn cells or peripheral nervous system myelin and that some individuals affected with this disease may present with clinical and electromyographic features suggestive of neonatal spinal muscular atrophy. PMID- 7998781 TI - High-dose dextromethorphan in amyotrophic lateral sclerosis: phase I safety and pharmacokinetic studies. AB - Much interest has focused on the role of glutamate-mediated excitotoxicity in the etiopathogenesis of amyotrophic lateral sclerosis (ALS). We therefore conducted a phase I study of high-dose dextromethorphan (DM) in ALS. DM is a selective, noncompetitive antagonist of the N-methyl-D-aspartate subtype of the glutamate receptor. Thirteen patients were given DM in an escalating dose fashion, to a target of 10 mg/kg/day or the maximum tolerable dose, and then maintained on this dose for up to 6 months. Total daily doses ranged from 4.8 to 10 mg/kg (median, 7 mg/kg). Side effects were dose limiting in most patients. The most common side effects were light-headedness, slurred speech, and fatigue. Detailed pharmacokinetic and neuropsychology studies were performed. This study demonstrates the feasibility of long-term administration of high-dose DM in ALS, as well as in other conditions associated with glutamate excitotoxicity. PMID- 7998782 TI - Hippocampal neuronal loss and regional hypometabolism in temporal lobe epilepsy. AB - The pathophysiology of widespread interictal hypometabolism in temporal lobe epilepsy is unknown but might reflect neuronal loss and diaschisis. We found no significant correlation between any cortical region's metabolism on preoperative [18F]fluorodeoxyglucose positron emission tomography and neuronal density of resected hippocampi in 40 patients. We conclude that hippocampal neuronal loss and diaschisis cannot account for the regional interictal hypometabolism of temporal lobe epilepsy. PMID- 7998783 TI - Neuropathologic correlates of persistent neurologic deficit in lithium intoxication. AB - While acute neurological symptoms complicating lithium therapy are well recognized, persistent neurologic dysfunction is uncommon. Regardless of the duration of symptoms, neuropathological correlates of lithium toxicity are few. We report the case of a 67-year-old man who developed lithium toxicity manifested by encephalopathy and coma followed by persistent dysarthria and ataxia. Autopsy revealed neuronal loss and gliosis in the cerebellar cortex and dentate nuclei; the cerebellar white matter exhibited prominent spongy change. Persistent cerebellar syndrome may occur with lithium intoxication and should be considered in the differential diagnosis of chronic cerebellar dysfunction. PMID- 7998784 TI - Limitations of magnetic resonance spectroscopy in patients with white matter disease. PMID- 7998785 TI - Descriptive epidemiology of multiple sclerosis in Europe in the 1980s: a critical overview. AB - The oversimplified but commonly accepted belief, based on the comparison of the prevalence studies conducted until 1980, that the distribution of multiple sclerosis (MS) in Europe is related to latitude has been contradicted by a great number of prevalence and incidence studies carried out since 1980. The most recent studies, based on more appropriate methods, clearly indicate that the MS distribution in Europe is much more complex than supposed in the past. The MS distribution in Europe now appears to be very uneven, with great variations not only between areas at the same latitude, but also within the countries themselves. However, even the most recent European studies cannot be reliably compared because of differences in the denominator characteristics, case ascertainment accuracy, diagnostic criteria, and definitions of prevalence and incidence. Despite these problems, descriptive data since 1980 indicate that ethnicity plays an important role in determining the European MS distribution. Furthermore, variations in both prevalence and incidence rates in ethnically homogeneous populations confirm the i importance of environmental factors in determining the primary acquisition of the disease. Further descriptive studies based on more comparable methods and better control for ethnicity would more precisely define the role of genetic susceptibility as well as suggest more valuable clues regarding environmental factors affecting the primary acquisition of MS. PMID- 7998786 TI - Multiple sclerosis in Iceland, with observations on the alleged epidemic in the Faroe Islands. AB - The profile of multiple sclerosis (MS) in Iceland based on a total population study from 1900 to 1990 is reviewed. The first survey in the late 1950s was a retrospective one. Since then, there has been a continuous prospective study that extends over a period of 40 years. The incidence of MS, which was 2.5/100,000 in the 1930s, rose to 3.5 to 4.1/100,000 between 1975 and 1990, but the data from the 1930s must be considered unreliable. There was a similar stepwise increase in prevalence from 30 to approximately 100/100,000 in 1990. It is most likely that the changes in prevalence are the result of improved case ascertainment, the growing number of well-trained neurologists in the country, and the greater awareness of the disease due to the activities of the Icelandic MS Society. No local or regional clusters were identified, but from 1900 to 1980 there was a steady and unexpected increase in the number of cases in rural areas, both by date of clinical onset and date of putative disease acquisition. No evidence was found to support the hypothesis that an epidemic of MS had occurred in Iceland following the arrival of British, Canadian, and American troops during the Second World War. The proposed epidemic in the Faroe Islands was also reexamined, in particular because of the identical ethnic, historical, demographic, and geographical similarities with Iceland. The available data are not supportive of that idea. PMID- 7998787 TI - The epidemiology of multiple sclerosis: a general overview. AB - Epidemiological studies of multiple sclerosis (MS) have shown the importance of genetic susceptibility factors that are modified by as yet unknown environmental influences. The often-cited interrelation between prevalence and latitude is no longer viable, with the important but unexplained exception of Australia and New Zealand. The standardization and increasing use of uniform diagnostic criteria lend new credibility to the results of MS surveys. More precise criteria are offered for symptoms of disease onset, Devic's syndrome, and progressive disease. The role of magnetic resonance imaging in the diagnosis of MS, and the pitfalls of its abuse, are reviewed. Reports of epidemics of MS are examined and discarded because they are based on the biologically meaningless date of diagnosis or that of onset, rather than when MS was probably acquired, that is, before puberty. The concept of onset-adjusted prevalence suggests that patients who are symptomatic should be included retrospectively in epidemiological surveys, even before they have been formally diagnosed as having MS, but individuals who were symptomatic before moving to a study area should not. The importance of ethnic homogeneity of patients and control subjects cannot be overemphasized in prevalence and risk factor studies. In the latter, close attention must be paid to biological plausibility and to prudent statistical interpretation. The hypothesis of the MS trait describes a systemic, asymptomatic condition that does not affect the nervous system, and may explain the low concordance of the disease in monozygotic twins. PMID- 7998788 TI - Genetic epidemiology of multiple sclerosis: a survey. AB - The possible role of genetic factors in the etiology of multiple sclerosis (MS) has been debated for over a century. It is now clear that genetic and environmental interactions must exist. It is likely that MS susceptibility is under the control of several genes encoded both within and outside the major histocompatibility complex (MHC). It is therefore unlikely that MS has a purely transmissible cause for these and other reasons, including the low concordance rate in dizygotic twins, low concordance rate in conjugal pairs, negative birth order in multiplex MS sibships, the relatively high rate of MS in second- and third-degree relatives of MS patients, and the identification of groups resistant to MS in otherwise high-risk areas. PMID- 7998789 TI - Genetic susceptibility to multiple sclerosis. AB - Twin studies have established that susceptibility to multiple sclerosis (MS) is partly genetic. Attempts to identify the relevant genetic loci have involved population-based studies, to detect associations between a genetic marker and MS, and family studies, to detect linkage between a putative marker and MS. Most of this genetic work is driven by the view that MS is an autoimmune disease. Thus, the focus has been mainly on genes known to be important in the immune response: human leukocyte antigen (HLA) genes, T-cell receptor genes, and immunoglobulin genes. To date, only the particular HLA-DR2 haplotype that is common in Caucasians can be concluded to be important in MS susceptibility in most populations. Studies of other genetic loci have been few, the data obtained often have been conflicting or controversial, and further studies are needed to clarify the biological significance of these loci in MS. Recommendations for further studies are provided in order to overcome some of the problems that have plagued earlier work in MS such as nonreproducibility of results. PMID- 7998790 TI - The epidemiology of multiple sclerosis: principles, achievements, and recommendations. PMID- 7998791 TI - Use and misuse of statistics for epidemiological studies of multiple sclerosis. AB - Despite a vast literature on the epidemiology of multiple sclerosis, the cause of this disease remains elusive. The majority of the studies have focused on prevalence, so that a worldwide distribution of multiple sclerosis can now be mapped. Tantalizing apparent differences in prevalence have resulted in an abundance of hypotheses about risk factors for multiple sclerosis, none of which have been firmly established. This article reviews the difficulties inherent in the use of any type of descriptive study to investigate etiology of disease and provides an update of appropriate statistical methodology to analyze study results. The major focus is on the use of analytical study design, specifically the case-control study, to investigate a specific hypothesis about association between a risk factor and multiple sclerosis. An update on new epidemiological and statistical methodology to enhance the design of future case-control studies is presented. Future opportunities to study multiple sclerosis in new ways, such as in cohort studies or nested case-control studies, using large medical insurance and other types of health-related data bases, are discussed. PMID- 7998792 TI - The dissemination of multiple sclerosis: a Viking saga? A historical essay. AB - The highest prevalence rates for multiple sclerosis are found in Iceland, Scandinavia, the British Isles, and the countries settled by their inhabitants and their descendants, that is, the United States, Canada, Australia, and New Zealand. This suggests that the Vikings may have been instrumental in disseminating the genetic susceptibility to the disease in those areas as well as in other parts of the world. The Vikings raided in most European countries and settled in Normandy and in Sicily and southern Italy. They engaged in trade with the Arabs along the river routes to the Caucasus and to the Black and Caspian Seas and penetrated into Persia, India, and probably China. They also migrated to the East and established the Russian state. Under the name Varangians, they became part of the Byzantine army and were active in all of the military activities of the Byzantine Empire. They participated in the Crusades. Russians, many of Scandinavian origin, also constituted a regiment of the Mongol army and roamed throughout that empire as well. The custom of capturing and keeping or selling women and children, which was widespread in the early Middle Ages, as well as the flourishing slave trade in men, were important factors in this genetic dissemination. PMID- 7998793 TI - Let's keep our eyes on the big picture--the restructuring and reorganizing of health care delivery. PMID- 7998794 TI - Trauma centers could be the next extinct species. PMID- 7998795 TI - Recycling revisited. PMID- 7998796 TI - Recycling revisited. PMID- 7998797 TI - Traumatic atlantooccipital dislocation injury in children. AB - The tragedy of trauma turns into triumph when the surgery team members' efforts result in victory for the patient. Nowhere is this more true than in successful pediatric trauma care. Giving a child a second chance at life and the family an opportunity for a new beginning is the highest reward for the trauma team's years of professional training and practice. Traumatic atlantoocipital dislocation injury usually results in death, but recent neurosurgery trauma advances are increasing pediatric survival rates. PMID- 7998799 TI - The OR suite as a unique trauma resuscitation bay. AB - Trauma is the fourth leading cause of death in the United States, and trauma injuries affect more than 50 million Americans annually. Inadequate care of trauma patients can cause unnecessary patient deaths. To decrease death and disability caused by trauma, one Denver hospital developed a trauma OR based on the "Golden Hour" principle (ie, the sooner a patient receives treatment, the more likely the patient will survive). Since 1977, this hospital has performed 1,838 trauma resuscitations in the trauma OR suite. This article discusses the importance of triage and recants the history of trauma patient transportation. The authors detail the trauma procedures at their hospital, including the specific roles of trauma team members and the necessary equipment, and provide demographic information on the trauma resuscitations performed at the hospital since 1988. The article also discusses the extensive and continuous orientation necessary for trauma team members and explains the quality improvement strategies implemented by this hospital. PMID- 7998798 TI - Perioperative care of the pediatric trauma patient. AB - Children have specific emotional and physiological needs that are intensified when they sustain injuries that require surgery. Care of pediatric trauma patients includes the physiological considerations of airway management, hemodynamic stability, hypothermia, and physical size. Psychological considerations include enhancing coping skills, caring for children according to their developmental levels, and caring for family members. The perioperative nurse must be familiar with these pediatric trauma nursing principles to effectively meet the needs of children and their family members during times of trauma crisis. PMID- 7998800 TI - Clinical forensics for perioperative nurses. AB - Perioperative nurses frequently care for victims and suspected perpetrators of violent crimes. Nurses often are the first health care providers to assess the trauma patient and collect crucial evidence for future legal action. Informational evidence includes observations about patients' behavior and appearance and documentation of their comments. Nurses also must protect the chain of evidence so that evidence can be admissible in court. To function in this role, perioperative nurses must understand the concepts of clinical forensics, which is the application of the principles and practices of forensic science to questions of law in the investigation of violent crime. PMID- 7998801 TI - Implementation of an event-related sterility plan. AB - A paradigm shift from a time-related sterility method to an event-related sterility assurance plan is possible if the nurse manager's approach to OR staff members is well researched and properly presented. Following research protocols and providing a methodology and rationale to staff members will enhance the success of the implementation process. A successful paradigm shift to an event related sterility system has the potential of increasing knowledge, improving practice, empowering staff members, and saving money, time, and effort. PMID- 7998802 TI - Proposed AORN position statement on perioperative care of patients with do-not resuscitate (DNR) orders. Association of Operating Room Nurses. PMID- 7998803 TI - AORN Special Committee on Environmental Issues reports environmental survey results. PMID- 7998804 TI - Dehydration in the elderly surgical patient. PMID- 7998805 TI - Labor law may be affected by federal commission's findings. PMID- 7998806 TI - Bipartisan proposal addresses cost containment and gradual health care reform. PMID- 7998808 TI - 1993-1994 president's report: state of the association 9,000 members and growing: 25 years of successful service to nephrology nursing. PMID- 7998807 TI - Lipase from a Brazilian strain of Penicillium citrinum. AB - A lipases (glycerol ester hydrolases E. C. 3.1.1.3) from a brazilian strain of Penicillium citrinum has been investigated. When the microorganism was cultured in the simple medium (1.0% olive oil and 0.5% yeast extract), using olive oil in as carbon source in the inocula, the enzyme extracted showed maximum activity (409 IU/mL). In addition, decrease of yeast extract concentration also reduces the lipase activity. Nevertheless, when yeast extract was replaced by ammonium sulfate, no activity was detected. Purification by precipitation with ammonium sulfate showed best activity in the 40-60% fraction. The optimum temperature for enzyme activity was found in the range of 34-37 degrees C. However, after 30 min at 60 degrees C, the enzyme was completely inactivated. The enzyme showed optimum at pH 8.0. The dried concentrated fraction (after dialysis and lyophilization) maintained its lipase activity at room temperature (28 degrees C) for 8 mo. This result in lipase stability suggests an application of lipases from P. citrinum in detergents and other products that require a high stability at room temperature. PMID- 7998809 TI - Health care reform and nursing's window of opportunity: an interview with Connie Curran. Interview by Terran Warren Sims. AB - The debate over how changes expected in health care reform will affect the role of nursing in providing patient care is the hottest topic in nursing circles this year. Clearly, patient care will not be delivered in the same manner 5 years from now as it is today. In this interview, Connie Curran, EdD, RN, FAAN, editor of Nursing Economic$ and a highly regarded nursing consultant, discusses many aspects of the health care reform debate, including the future of academic health centers, nursing's and medicine's role in shaping the language of health care reform, the battle for fewer jobs, paths of professional development, and effects of reform on nursing research. Dr. Curran, who will serve as keynote speaker for ANNA's 25th Anniversary National Symposium in Dallas, TX this June, was interviewed by ANNA President Terran Warren Sims at the Nursing Economic$ office in Washington, DC. The former executive director of the American Organization of Nurse Executives (AONE), Dr. Curran has lectured on the effects of health care reform to audiences around the country. She is currently serving a 1-year appointment as a senior scholar in residence at the Institute of Medicine, which is studying various aspects of health care reform. PMID- 7998810 TI - 1993-1994 national directory of certified nephrology nurses. PMID- 7998811 TI - Case study of the anemic patient: epoetin alfa--focus on exercise. AB - Physical functioning of patients with chronic renal failure is often low. An exercise program can enhance their capacity for physical activity and thus improve their quality of life. Dialysis staff can use a four-step approach to develop strategies to encourage exercise. In addition, staff support can help motivate patients to take part in exercise programs. PMID- 7998812 TI - Changes in adolescents' sexuality between 1970 and 1990 in West-Germany. AB - Based on two studies (using semistructured interviews) of 16- and 17-year-old West German urban adolescents, the first in 1970 (N = 602) and the second in 1990 (N = 415), this paper traces the changes in young people's sexual behavior and attitudes during the past two decades: (i) The marked trend in the 1960s towards having coitus and petting at an ever earlier age does not seem to have continued; the changes noted in the incidence of heterosexual experiences since 1970 are minimal. (ii) Boys feel themselves less at the mercy of their sexual urges than they used to and tend to link sexuality with love and a steady relationship more than they did 20 years ago; there was a similar though less pronounced change among girls. (iii) Girls now get less pleasure and satisfaction out of sexual encounters, and in heterosexual situations take the initiative and control more than they used to. (iv) There is no evidence that the problem HIV/AIDs had a marked influence on the changes described. Results of the comparative studies are discussed in the context of current developments in man/woman relationships and the debate on gender issues. PMID- 7998813 TI - Women in relationships with cross-dressing men: a descriptive study from a nonclinical setting. AB - Over a 6-year period, 106 women involved with men who cross-dress (mostly heterosexual transvestites) completed a questionnaire regarding themselves, their male partners, and their relationships. Interview data supplemented these questionnaires for 75% of the respondents. All respondents were recruited from nonclinical settings. The "modal" female partner was a 40-year-old Protestant, Caucasian woman, who was a firstborn child, in her first marriage. She was more likely than other women her age to be childless, and to have earned at least a 2 year college degree. She was no more likely to have had lesbian experiences or substance use problems than comparably aged American women. She had been married to her cross-dressing mate for 13 years and had known of his activities for 9 years. A quarter of women reported at least occasional sexual arousal to their mate's cross-dressing. The two variables associated with low acceptance of cross dressing were discovery of their partner's cross-dressing after marriage and lack of sexual arousal to cross-dressing stimuli. Low acceptance was unrelated to firstborn status, amount of exposure to cross-dressing activities, or having had children. This group may be more representative of women in relationships with cross-dressing men than previous reports limited to cross-dressers and spouses who are in treatment. PMID- 7998814 TI - Sexual behavior research on a cohort of gay men, 1984-1990: can we predict how men will respond to interventions? AB - In 1984, over 1000 gay and bisexual men volunteered to participate in both the Chicago Multicenter AIDS Cohort Study (MACS) and a companion psychosocial study, the Coping and Change Study (CCS). Participants in the semiannual Chicago MACS/CCS evaluations comprise the largest cohort of high-risk men under continuous medical, behavioral, and psychosocial observation. Chicago MACS/CCS researchers prospectively chart the sexual behavior change patterns of the cohort and relate those behavioral changes to psychosocial correlates and actual HIV infection risk. This report summarizes the behavioral natural history of the Chicago MACS/CCS cohort from 1984 to 1990, focusing on receptive anal sex practices and use patterns for alcohol and the most frequently used recreational drugs. As these are prospective observational and not controlled intervention studies, psychosocial correlates of sexual behavior change by members of the cohort are suggestive of factors influencing behavior change rather than indicative of causal relationships. However, the voluntary availability to participants in the Chicago MACS/CCS of HIV-1 antibody test results beginning in late 1985 provided the opportunity to examine whether demographic, psychosocial, or behavioral factors were indicators of sexual behavior change following disclosure and counseling about HIV-1 serostatus. Recommendations for promotion and maintenance of safer sexual behavior for the long run, and limitations in the generalizability of these findings to the much more diverse populations of men who have sex with other men conclude this article. PMID- 7998815 TI - The basis of the abused abuser theory of pedophilia: a further elaboration on an earlier study. AB - The connection between the retrospective self-report of sexual abuse in childhood by an adult person, and (i) erotically preferred age bracket and (ii) type of offense, was investigated in 303 heterosexual males. This group consisted of 83 pedophilic sex offenders against female children, 52 sex offenders against female children who erotically preferred adult women, 34 sex offenders against adult women, and 134 volunteer controls. An earlier exploratory investigation with somewhat smaller numbers of individuals had rendered only ambiguous results. After regrouping of individuals and more precise analysis of results, the present study demonstrated that the self-report of having been sexually abused in childhood is mainly connected with pedophilia. Status as a sex offender in general was not related to childhood abuse. PMID- 7998816 TI - Opposite sex-linked behaviors and homosexual feelings in the predominantly heterosexual male majority. AB - Whether homosexual feelings are distributed categorically or dimensionally remains controversial. In an earlier series of studies, medical students anonymously reported a dimensional distribution of homosexual feelings, the ratio of homosexual to heterosexual feelings in men correlating with opposite sex linked behaviors in childhood and adolescence, and, in both sexes, with current degree of opposite sex identity. Prevalence of homosexual feelings was markedly higher than that found in nonanonymous studies. In the present investigation, a study of male twins allowed investigation of the findings in 411 educationally more representative subjects. Awareness of some homosexual feelings was reported in adolescence by 20% and currently by 12%. As with medical students, the majority of those who reported some homosexual feelings were predominantly heterosexual, which could be considered to indicate such feelings were distributed dimensionally. Correlations between degree of homosexual feelings and avoidance of contact sport in childhood and adolescence, current wish to be of the opposite sex, and opposite sex identity remained present when subjects with equally bisexual and predominantly homosexual feelings were excluded from analysis. The finding that the majority of men with homosexual feelings are predominantly heterosexual renders implausible the theory that homosexual feelings result from fear of heterosexuality. PMID- 7998817 TI - Menstrual cycle variation of women's interest in erotica. AB - Female respondents were given the opportunity to choose feature films for viewing. Choices were made on the basis of synopses and promotional videos. These materials projected (i) a focus on erotic, sexual events, (ii) romantic themes, (iii) action-packed violent drama, and (iv) hilarious comedy. Additionally, respondents evaluated the appeal of the projected films. Respondents' position in the menstrual cycle was then determined, with placement into one of seven 4-day phases. Measured in both choices and evaluations, a postmenstrual surge in erotic interest was evident. Erotic interest was also pronounced prior to and during menses. In contrast, it was at a minimum during the first half of the luteal phase. The choice of romantic films was not appreciably influenced by cycle position. However, in evaluating films with romantic themes, premenstrual women expressed particularly little interest in this genre. PMID- 7998818 TI - Erythroid progenitor cells that survive benzene exposure exhibit greater resistance to the toxic benzene metabolites benzoquinone and hydroquinone. AB - Benzene is a well known hematotoxicant which induces hematopoietic dyscrasias of varying intensities in different individuals and even in different strains of the same experimental animal species. Although there is ample evidence that diverse responses to benzene are related to differences in benzene metabolism, we have recently provided evidence implicating differences in host target cell susceptibility to these diverse responses to benzene. The present study extends our previous work and concerns strain-specific differences in marrow progenitor cells that survive benzene exposure. Two mouse strains (Swiss-Webster and C57B1/6J) which respond to benzene exposure with different intensities of bone marrow cytotoxicity were used. Bone marrow cells from benzene-exposed and untreated mice were cultured with one of five benzene metabolites: 1,4 benzoquinone (BQ), catechol (C), hydroquinone (HQ), muconic acid (MA) or phenol (P) and the abilities of these cells to produce erythroid (CFU-e) or granulocyte/macrophage colonies (GM-CFU-c) were assessed. In both strains, marrow cells isolated from benzene-exposed mice showed a higher percentage of plated CFU e surviving culture with BQ, HQ or MA than marrow cells isolated from control mice. In contrast, both strains of benzene-exposed mice displayed decreased percentages of plated CFU-e surviving culture with catechol than cells isolated from control mice. Only one condition (the culturing of cells with HQ under GM CFU-c forming conditions) showed any strain-specific difference in plating efficiency. In all, 20 possible combinations of benzene metabolites and cell types were examined (5 metabolites x 2 progenitor cell types x 2 strains).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7998819 TI - Aluminum effects on blood chemistry and long bone development in the chick embryo. AB - Body growth, blood chemistry, and long bone development of 10- to 16-day chick embryos (Gallus gallus) treated with aluminum (Al) citrate, sodium (Na) citrate, or sodium chloride (NaCl) were investigated. Two administration protocols were used. Acutely-treated embryos received 6.0 mumol Al citrate or Na citrate on day 8 of incubation. Chronically-treated embryos received a daily dose of 1.5 mumol Al citrate or Na citrate beginning on day 8 of incubation. For both protocols, Al citrate and Na citrate had no significant influence on viability or body weight. Al citrate-treated embryos had: (a) significantly shorter mean tibia lengths by day 16 of incubation, (b) a consistently lower ratio of tibia length: body weight on all days investigated, and (c) a persistent mid-diaphyseal malformation (angulation) of the femur and tibia. Spatially correlated with the malformation was a calcification defect detected by alizarin red S staining of intact tibias and the accumulation of aluminum as demonstrated by acid solochrome azurine staining of histological sections. Aluminum was localized at the mineralization front of the osteogenic collar surrounding the cartilage core of the tibia. Aluminum citrate or Na citrate had no significant effect on serum total calcium, inorganic phosphorus, total alkaline phosphatase activity, or creatinine, except for a transitory hypercalcemia (day 10) and phosphatemia (days 10 and 12) in Al citrate-treated embryos. The concomitant localization of Al and the early calcification defect in the region of tibial malformation implicate aluminum in the pathogenesis of the skeletal abnormality. PMID- 7998820 TI - Pulmonary clearance and inflammatory potency of intratracheally instilled or acutely inhaled nickel sulfate in rats. AB - Rats were exposed to nickel sulfate (NiSO4) either by intratracheal (IT) instillation or by acute aerosol inhalation, and pulmonary clearance of Ni and pulmonary inflammatory responses were studied. The half-time of Ni in the lung (initial lung burden = 50 micrograms Ni/rat) was about 32 h in both the IT instillation and inhalation groups. Ni retention in the lung tissue following IT instillation of NiSO4 was saturable with reference to dose, suggesting that clearance rate of Ni from the rat lung depends on lung burden of Ni. Lung inflammatory responses were evaluated by biochemical, elemental and cytological indicators in bronchoalveolar lavage fluid (BALF) following IT instillation of NiSO4. Activities of lactate dehydrogenase and beta-glucuronidase, contents of lysozyme, protein, sulfur and calcium, and the number of polymorphonuclear leukocytes were increased with a peak at 2-3 days post-instillation, while BALF alkaline phosphatase (ALP) activity was significantly decreased after IT instillation of NiSO4. Lung tissue ALP activity was also decreased by NiSO4. Because Ni does not inhibit ALP directly, the decrease in ALP activity is probably due to functional changes of type II cells (a major source of BALF ALP). Thiobarbituric acid reacting substances in the lung tissue were not changed by NiSO4, suggesting that lipid peroxidation plays a minimal, if any role, in the Ni induced inflammation in the rat lung. PMID- 7998821 TI - Effect of cadmium (CdCl2) on cell proliferation and production of EDRF (endothelium-derived relaxing factor) by cultured human umbilical arterial endothelial cells. AB - The effect of cadmium chloride (CdCl2) on cell proliferation and EDRF (endothelium-derived relaxing factor) production by cultured human umbilical arterial endothelial cells (HUAECs) was investigated. The viability of HUAECs decreased dose-dependently after the addition of Cd (cadmium chloride). Morphologic examination by phase contrast microscopy revealed severe damaging effects of Cd at higher concentrations. The cytotoxic effect of Cd on DNA synthesis was also concentration-dependent. The effect of Cd on EDRF production by indomethacin-treated HUAECs was assessed by its anti-platelet aggregatory effect. Platelet aggregation studies were carried out in cuvettes lined with HUAECs using an aggregometer. The anti-platelet aggregatory effect was decreased dose-dependently by pretreatment with Cd. These findings suggest that HUAECs are susceptible to concentration-dependent Cd cytotoxicity, and that Cd can inhibit the production of EDRF by HUAECs. PMID- 7998823 TI - Dopaminergic system activity and cellular defense mechanisms in the striatum and striatal synaptosomes of the rat subchronically exposed to manganese. AB - In 6-month-old male Wistar rats, levels of dopamine (DA), dihydroxyphenylacetic acid (DOPAC), ascorbic acid (AA), dehydroascorbic acid (DHAA), uric acid and glutathione (GSH) were determined by HPLC in the striatum and striatal synaptosomes after subchronic oral exposure to MnCl2 50-100-150 mg/kg. Mn significantly decreased levels of DA and GSH and increased levels of DHAA and uric acid both in the striatum and synaptosomes. In synaptosomes, individual total Mn doses/rat were directly correlated with individual DOPAC/DA ratio values (r = +0.647), uric acid (r = +0.532) and DHAA levels (r = +0.889) and inversely correlated with DA (r = -0.757) and GSH levels (r = -0.608). In turn, GSH levels were inversely correlated with uric acid (r = -0.451) and DHAA levels (r = 0.460). In conclusion, the response of striatal cellular defense mechanisms (increase in AA oxidation, decrease in GSH levels) correlated well with changes in markers of dopaminergic system activity and increase in uric acid levels. The latter provides evidence of an Mn-induced oxidative stress mediated by xanthine oxidase. PMID- 7998822 TI - Alteration of glycosaminoglycans induced by cadmium in cultured vascular smooth muscle cells. AB - Alteration of glycosaminoglycans (GAGs) in cultured bovine aortic smooth muscle cells after exposure to cadmium was investigated. It was revealed that cadmium increased the accumulation of GAGs metabolically labeled with [3H]glucosamine but decreased that with [35S]sulfate in the cell fraction, the cell surface fraction and the medium fraction. This suggested that cadmium stimulated the biosynthesis of GAGs but inhibited their sulfation in the cells. A similar alteration was observed in cadmium-treated human aortic smooth muscle cell layer. Of tested cations including cadmium, bismuth, cobalt, copper, lead, manganese, nickel and zinc, only cadmium stimulated [3H]glucosamine incorporation, with a strong inhibition of the [35S]sulfate incorporation in the bovine cells. Characterization of bovine smooth muscle GAGs showed that the cadmium-induced increase in the [3H]glucosamine incorporation was mainly observed in heparan sulfate; the inhibition of the [35S]sulfate incorporation occurred non selectively. Cadmium accumulated in bovine vascular smooth muscle cells in a dose dependent manner with an increase in the leakage of lactate dehydrogenase into the medium. The present data suggest that vascular smooth muscle cells respond to the cytotoxicity of cadmium and promote the GAG synthesis with a reduction of their sulfation. It is postulated that this response may be a defensive one to the damage of the vascular tissue caused by cadmium but would be a component of the metal-induced atherosclerosis. PMID- 7998824 TI - Cardiotoxicity of adrenochrome in isolated rabbit hearts assessed by epicardial NADH fluorescence. AB - Noradrenaline in a micromolar concentration has recently been shown to contribute to ischemic tissue injury by direct cardiotoxic effects independent of functional alterations. Oxygen free radicals, generated during the auto-oxidation of catecholamines, are important mediators of catecholamine cardiotoxicity. However, the role of the oxidative products (aminochromes) is still unclear. We examined the effects of adrenochrome on functional parameters and on regional myocardial ischemia (MI) in isolated electrically-driven rabbit hearts with depleted catecholamine stores (reserpine 7.0 mg/kg i.p. 16-24 h before preparation, Langendorff, constant pressure: 70 cm H2O, Tyrode solution, Ca++ 1.8 mmol/l, 37 degrees C). Repetitive MI, separated by a reperfusion period of 50 min, was induced by coronary artery branch ligature, and MI was quantitated from epicardial NADH fluorescence photography. Adrenochrome-treatment (10(-6) M or 10( 4) M) was started after a reperfusion period of 20 min. The left ventricular pressure (LVP) was significantly enhanced by adrenochrome (p < 0.05), but it fell thereafter to below its initial value in hearts treated with adrenochrome 10(-4) M. The global coronary flow (CF) was not affected by adrenochrome 10(-6) M (P > 0.05), but it was significantly decreased by adrenochrome 10(-4) M (P < 0.05). The relative CF (= CF/LVP x heart-rate) was numerically decreased by adrenochrome 10(-6) M (p > 0.05) and more markedly by adrenochrome 10(-4) M (p < 0.05). Whereas epicardial NADH fluorescence was similar after repetitive coronary artery occlusions in controls and in hearts treated with adrenochrome 10(-6) M (p > 0.05), it was significantly enhanced by adrenochrome 10(-4) M (p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7998825 TI - Ganglioside content of rat liver after administration of ethanol and pentazocine or sucrose supplemented diets. AB - In a previous paper, we determined the effect of either ethanol or pentazocine administered separately on the ganglioside content of rat liver. In the present paper we have investigated the effect of pentazocine injection on the liver ganglioside contents of chronic alcoholic rats. The effect of high carbohydrate ingestion was also studied. Thirty male Wistar rats were divided into three experimental groups that received ethanol and pentazocine, a carbohydrate supplemented diet or a laboratory diet and water. Liver ganglioside contents were slightly increased in the ethanol plus pentazocine group as compared to the control and high carbohydrate diet groups. No differences were found between the two latter groups. The percentage distribution of individual gangliosides (ganglioside pattern) was also modified. A decrease in gangliosides belonging to the b-series (GD3, GD1b, GT1b and GQ1b) in parallel with an increase in that of the a-series (GM2, GM1 and GD1a) were found for both the ethanol plus pentazocine and the high-carbohydrate fed rats. The results suggest that ethanol or high carbohydrate ingestion diminishes the activity of GD3 synthase, a key enzyme in the metabolism of gangliosides, which determines the proportion of gangliosides, belonging to the a- and b-series. PMID- 7998826 TI - Oxidation pathways for the intracellular probe 2',7'-dichlorofluorescein. AB - The oxidation of 2',7'-dichlorofluorescin (DCFH) to a fluorescent product is currently used to evaluate oxidant stress in cells. However, there is considerable uncertainty as to the enzymatic and nonenzymatic pathways that may result in DCFH oxidation. Iron/hydrogen peroxide-induced DCFH oxidation was inhibited by catalase or by the hydroxyl radical scavenger dimethylsulfoxide; however, superoxide dismutase (SOD) had no effect on DCFH oxidation. The formation of hydroxyl radical (indicated by the oxidation of salicylic acid to 2,3-dihydroxybenzoic acid) was proportional to DCFH oxidation, suggesting that the hydroxyl radical is responsible for the iron/peroxide-mediated oxidation of DCFH. Utilizing a superoxide generating system consisting of hypoxanthine/xanthine oxidase, oxidation of DCFH was unaffected by SOD, catalase or desferoxamine, and stimulated by removing hypoxanthine from the reaction mixture. In contrast, SOD or elimination of hypoxanthine abolished superoxide formation. In addition, potassium superoxide did not support the oxidation of DCFH. Thus, superoxide is not involved in DCFH oxidation. Boiling xanthine oxidase eliminated its concentration-dependent oxidation of 1 microM DCFH, indicating that xanthine oxidase can enzymatically utilize DCFH as a high affinity substrate. Kinetic studies of the oxidation of DCFH by xanthine oxidase indicated a Km(app) of 0.62 microM. Hypoxanthine competed with DCFH with a Ki(app) of 1.03 mM. These studies suggest that DCFH oxidation may be a useful indicator of oxidative stress. However, other types of cellular damage may produce DCFH oxidation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7998827 TI - Inhalation toxicokinetics of butoxyethanol and its metabolite butoxyacetic acid in the male Sprague-Dawley rat. AB - A total of 16 male Sprague-Dawley rats were continuously exposed to 20 ppm or 100 ppm butoxyethanol (BE) vapor for 1, 2, 3, 4, 6, 8, 10, or 12 days. Urine was collected in 24-h intervals and stored at -70 degrees C. At the end of the exposure the animals were euthanized by decapitation and tissue samples of blood, muscle, liver and were rapidly collected and frozen to -70 degrees C. The samples were later derivatized and analyzed for BE and its major metabolite butoxyacetic acid (BAA) by electron capture gas chromatography. BE and BAA were rapidly distributed to the tissues examined. The concentration of BE in blood was slightly higher, and that of BAA markedly higher than in other tissues, indicating weak (BE) and pronounced (BAA) blood protein binding, respectively. BE was efficiently metabolized and the blood clearance averaged 2.6 l/h per kg, corresponding to a hepatic extraction ratio of about 0.75. The renal clearance of BAA (average 0.53 l/h per kg) corresponded to approximately 15% of the renal blood flow. The kinetics of BE and BAA were linear up to 100 ppm. There were no clear indications of changes in the toxicokinetics, such as metabolic induction or inhibition of metabolism or excretion, during the course of the exposure. The recovery of BAA in urine was 64% of the calculated inhaled amount of BE, on an equimolar basis. PMID- 7998828 TI - Porphyrin studies in TCDD-exposed workers. AB - 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) has been shown to inhibit uroporphyrinogen decarboxylase activity resulting in chronic hepatic porphyria. From a cross-sectional study of 170 workers in chemical industry 68 showed elevated coproporphyrin levels, interpreted as secondary coproporphyrinuria. Three persons suffered from chronic hepatic porphyria in subclinical stages. None of the workers showed an overt porphyria cutanea tarda. A low-grade zinc protoporphyrinemia was observed in three persons. Forty-three of the 170 workers were evaluable for investigating the effect of TCDD on porphyrin levels. No significant correlation was found between TCDD concentration in adipose tissue and the level of uroporphyrin and coproporphyrin. The influence of a chloracne history is described. PMID- 7998829 TI - Expression and characterization of baculovirus expressed herpes simplex virus type 1 glycoprotein L. AB - We have constructed a recombinant baculovirus expressing high levels of the herpes simplex virus type 1 (HSV-1) glycoprotein L (gL) in Sf9 cells. Sf9 cells infected with this recombinant virus synthesized three polypeptides of 26-27 kDa 28 kDa, and 31 kDa. The 28 and 31 kDa species were sensitive to tunicamycin and N glycosidase F (PNGase F) treatment, suggesting that they were glycosylated. As shown by both indirect immunofluorescence and Western blot analysis, using polyclonal antibodies to synthetic gL peptides indicated that the baculovirus expressed gL was abundant on the surface of baculovirus gL infected Sf9 cells. A small fraction of the 31 kDa polypeptide was secreted into the extracellular medium as judged by Western blot analysis. The secreted form of gL was completely resistant to Endoglycosidase H (Endo-H), while the membrane associated form of gL was only partially resistant to Endo-H treatment, suggesting that the secreted gL represented a subpopulation of the membrane bound gL. Mice vaccinated with baculovirus expressed gL produced serum antibodies that reacted with authentic HSV-1 gL. However, these mice produced no HSV-1 neutralizing antibody (titer < 1:10) and they were not protected from lethal intraperitoneal or lethal ocular challenge with HSV-1. Thus, when used as a vaccine in the mouse model, gL, similar to our findings with HSV-1 gH, but unlike our results with the other 6 HSV-1 glycoproteins that we have expressed in this baculovirus system, did not provide any protection against HSV-1 challenge. PMID- 7998831 TI - Analysis of the population structure of three phenotypically different PSTVd isolates. AB - Phenotypically dissimilar greenhouse isolates from a Polish collection of potato spindle tuber viroid (PSTVd) were analysed. Partially purified PSTVd genomic RNAs from severe, intermediate and mild isolates was reverse transcribed and the resulting cDNAs enzymatically amplified. Abutting-primer PCR (Ab-P PCR) technology was used to obtain, in a single step, infectious full-length PSTVd cDNA monomers and these were sequenced. The mild isolate was found to be composed of a unique molecular variant (M), closely related to previously described PSTVd mild isolates. In the intermediate isolate, three variants, i2, i3 and i4, were detected. The severe isolate was found to be a mixture containing at least four molecular variants: s23, s27, i4 and i2. Infection of test plants with plasmids carrying monomeric cDNAs corresponding to each of the cloned variants confirmed that they are infectious. In addition, variant M produced mild symptoms, variants i2, i3, i4 intermediate symptoms and variants s23 and s27 severe symptoms. Therefore, the disease symptoms produced by a mixture are determined by the severe variants, masking the presence of milder ones. All the variants detected (except i2 which is identical to previously described PSTVd-DI) represent novel PSTVd sequences with point mutations located in the V and/or P domains. In particular, variants s23 and i4 represent shorter (358 nucleotides) versions of the PSTVd genome. PMID- 7998830 TI - Sequence comparison of the non-structural genes of four different types of Aleutian mink disease parvovirus indicates an unusual degree of variability. AB - The present work shows that at least four different sequence types of Aleutian mink disease parvovirus (ADV) are present in ADV isolates from mink. We here report the nucleotide sequences of these four types of ADV from nucleotide 123 to 2208 (map unit 3 to 46). This part of the genome encodes three non-structural (NS) proteins of ADV. Comparison of the deduced amino acid sequences of these NS proteins showed that the ADV proteins are much less conserved than the NS proteins from other members of the autonomous group of parvoviruses. In general, we found that the middle region of the ADV NS-1 protein was relatively well conserved among the types, while both the amino- and carboxy-terminal ends of the protein had higher amino acid variability. Interestingly, the putative NS-3 protein from type 3 ADV is truncated in the carboxy-terminal end. The molecular evolutionary relationship among the four types of ADV was examined. This analysis, taken together with the unusually high degree of variability of the ADV types, indicates that the ADV infection in mink is likely to be an old infection compared to the other parvovirus infections or, alternatively, that ADV accumulates sequence changes much faster than other parvoviruses. PMID- 7998833 TI - The induction of in vivo superinfection and recombination using feline immunodeficiency virus as the model. AB - This study investigated the hypothesis that under certain conditions, superinfection of cats with feline immunodeficiency virus (FIV), may occur. One FIV isolate (T91) was used to inoculate three FIV and FeLV-free cats. Blood from an FIV-infected cat (N), which contained two variants and differed from T91 by at least 5% in nucleotide sequence in the env gene, was inoculated into a fourth cat. Both T91 and blood from N were inoculated simultaneously into a fifth cat. After 22 weeks, two of the three cats initially infected with T91 were challenged with blood from N. At 30 weeks following initial infection, peripheral blood mononuclear cells were obtained from all cats, DNA was extracted, and a segment of the env gene was PCR amplified, cloned and sequenced. Nucleotide sequence analysis of the cloned PCR product showed that virus strains used in initial infection were recovered from cats not challenged with a second variant. Challenge of cats with the blood of N following initial infection with T91 resulted in superinfection occurring in one cat and recombination occurring in the other. Furthermore, the use of blood as a source of challenge, in cats where superinfection and simultaneous infections were attempted, may have induced the appearance of variants which more closely resembled the most heterologous strain present in the infectious source. PMID- 7998832 TI - Serum IgA immune response to individual rotavirus polypeptides in young children with rotavirus infection. AB - A human IgA-radioimmunoprecipitation assay (IgA-RIPA) utilizing the galactose binding lectin jacalin from the jack-fruit Artrocarpus integrifolia was developed. Among the human immunoglobulins, jacalin binds specifically to immunoglobulin A. The IgA-RIPA was used to characterize the serum IgA response to individual rotavirus polypeptides in nine paired sera from children (8-34 months of age) with an acute rotavirus infection. In acute sera the IgA response was mainly directed against the inner capsid proteins VP2 and VP6, with VP2 surprisingly being the most immunogenic protein while in the convalescent sera, the IgA response was directed not only against structural but also against non structural proteins. PMID- 7998834 TI - Rearrangement of intermediate filament network of BHK-21 cells infected with vaccinia virus. AB - Association between vaccinia virus (VV) structures and intermediate filaments in specific areas of the cytoplasm of infected cells (virus "factories") suggests that VV infection interferes with the cellular architecture by modifying the intermediate filament network. To analyse this question, we examined the array of intermediate filaments of BHK-21 cells infected with VV by laser scanning confocal microscopy using an anti-vimentin mouse monoclonal antibody. We observed a marked reorganization of intermediate filaments around the nucleus of infected cells. Bidimensional analysis of 32PO4-labeled intermediate filament proteins revealed that the acidic isoform of vimentin and two isoforms of desmin have increased phosphorylation levels in infected cells. Our results suggest that the reorganization of intermediate filaments observed during VV infection could be promoted by an increase in the phosphorylation level of the intermediate filament proteins, vimentin and desmin. PMID- 7998835 TI - Electron microscopic and molecular characterization of turnip vein-clearing virus. AB - We recently isolated turnip vein-clearing virus (TVCV), a tobamovirus which causes vein clearing in Brassica rapa (turnip) and a mosaic in Nicotiana tabacum (tobacco). We present an electron microscopic and molecular characterization of TVCV. Viral particles from lower epidermis peel contained rod-shaped viral particles, typical of tobamoviruses. Viral RNA extracted from infected turnip leaves was used as template for cDNA synthesis prior to cloning in a plasmid vector. Inserts of selected cDNA clones were sequenced to obtain the nucleotide sequence of the 126 K replicase component. The nucleotide and predicted amino acid sequences were 56 to 59% identical to those of most other sequenced tobamoviruses. The least related sequence, that of cucumber green mottle mosaic virus, was more related to the TVCV lineage than it was to those of the other sequenced tobamoviruses. UV spectroscopy suggested a tryptophan content characteristic of the ribgrass mosaic virus (RMV) group. Fragmentation of the TVCV coat protein by cyanogen bromide treatment produced a profile of fragments indistinguishable from those generated from the coat protein of RMV. Thus, while symptoms of TVCV infection on Nicotiana tabacum cv. Samsun and Nicotiana clevelandii differ from those reported for RMV, TVCV appears to be closely related to RMV. PMID- 7998836 TI - Expression and characterisation of the influenza A virus non-structural protein NS1 in yeast. AB - The influenza A virus non-structural protein NS1 was produced using a copper inducible expression system in the yeast Saccharomyces cerevisiae. The protein produced had a molecular weight of 26 kDa by SDS-PAGE and was reactive with anti NS1 antisera. The recombinant NS1 protein was targetted to the nucleolus/nuclear envelope fraction of the yeast cell nucleus, showing that its localisation signals remain functional in yeast. In addition, immune-electron microscopy detected cytoplasmic inclusions reminiscent of those seen in cells infected with some influenza strains. The NS1 protein was shown to be capable of in vivo self interaction which probably forms the basis of its propensity to form inclusions. Expression of the protein was found to be toxic to yeast cells expressing it, supporting a role for the protein in the shutdown of influenza virus-infected cells. Deletion mapping of NS1 pointed to 2 regions of the molecule being important for this toxicity: a basic C-terminal stretch which has been shown to act as a nuclear localisation signal, and an N-terminal region implicated in RNA binding. PMID- 7998837 TI - Constructions of vaccinia virus A-type inclusion body protein, tandemly repeated mutant 7.5 kDa protein, and hemagglutinin gene promoters support high levels of expression. AB - We devised vaccinia virus (VV)-based vector systems that support higher levels of expression of cloned genes in the early and late phases of the infection cycle than reported previously. Enhanced expression can be obtained by combining the promoter of the A-type inclusion body protein gene, the mutated early region of the 7.5-kDa gene promoter (7.5-kDa promoter), and the promoter of the hemagglutinin (HA) gene. One construct produced 60 micrograms/10(6) cells of chloramphenicol acetyltransferase (CAT), equivalent to 10-18% of total cell protein. Another construct produced about seven times more CAT during the early phase than the amount synthesized under the control of the 7.5-kDa promoter alone. The envelope proteins of human immunodeficiency virus type I synthesized during the early phase of infection were more active as immunogens than these proteins synthesized during the late phase, regardless of the amounts produced. PMID- 7998838 TI - Characterization of a reovirus isolate from a rattle snake, Crotalus viridis, with neurological dysfunction. AB - A virus isolate from the brain of a rattle snake with central nervous system (CNS) symptoms was identified as a reovirus. The isolate did not agglutinate pig erythrocytes and was not neutralized by antisera against avian reovirus S1133 and mammalian reovirus type 3. The cytopathic effect in Vero cells was characterized by formation of syncytial giant cells. Electrophoretic analysis of the genome revealed 10 segments of dsRNA. The isolate displayed characteristics distinct from avian and mammalian reoviruses. PMID- 7998839 TI - Structure and function of the long terminal repeat of the chimpanzee foamy virus isolates (SFV-6). AB - The complete long terminal repeat (LTR) nucleotide sequence of the chimpanzee foamy virus isolate SFV-6 was determined. Its 1761-bp size makes it the longest LTR reported to date among all retroviruses. Since the length of its LTR is similar to that of other simian isolates while its sequence homology is closer to that of HFV, SFV-6 genetic structure appears to be intermediate between simian and human foamy viruses. Transient expression assays demonstrate that SFV-6 encodes a transactivator of viral gene expression directed either by its own LTR or by heterologous promoters like HFV and HIV-1 LTRs. Our data also provide evidence for cross-transactivation between SFV-6 and HFV. PMID- 7998841 TI - A densovirus newly isolated from the smoky-brown cockroach Periplaneta fuliginosa. AB - We purified a causing agent of fetal disease for smoky-brown cockroach Periplaneta fuliginosa, which was designated as "cockroach small spherical virus (CSSV)". Purified virus particles had a diameter of 22 +/- 0.6 nm and contained DNA as a single-stranded form. However, the extraction of DNA under condition of appropriate high salt and elevated temperature yielded a double-stranded DNA with a size of 5,500 nucleotides. These results were quite similar to those of other densoviruses (DNVs). The CSSV had five structural proteins (VP1: 52 KDa, VP2: 56 KDa, VP3: 79 KDa, VP4: 82 KDa, and VP5: 105 KDa). The SDS-PAGE profile of these proteins was quite different from that of the cockroach DNV previously reported and was rather similar to that of Bombyx mori (Bm) DNV-1. An immunochemical study, however, demonstrated that there was no immunological relationship between the CSSV and the Bm DNV-1. These data suggest that the CSSV is a new member of DNV. PMID- 7998840 TI - Rotaviruses belonging to the AU-1 genogroup recovered from Israeli infants with diarrhea. AB - The genetic and antigenic diversity of group A rotaviruses recovered from Israeli infants has been expanded recently by the inclusion of three unusual human rotavirus strains. Two rotavirus strains (Ro-5829 and Ro-5960) were shown to be the first viruses outside Japan that resembled the AU-1 genogroup of feline like human rotaviruses in their overall genomic constellation and in the restriction pattern of their polymerase chain reaction amplified gene 4 following digestion with EcoRI. Another strain (Ro-5193) turned out to be an intergenogroup reassortant between viruses belonging to the AU-1 and the bovine genogroups and resembled in that respect similar viruses isolated from infants in Italy. PMID- 7998842 TI - Bovine cutaneous papillomas associated with bovine papillomavirus type 5. AB - Squamous papillomas obtained from bovine facial skin yielded viral DNA indistinguishable from that of bovine papillomavirus type 5. It was separated from recognised bovine papillomaviruses by its restriction endonuclease pattern and hybridization tests with DNA. PMID- 7998843 TI - Isolation of the missing 5'-end of the encoding region of the bovine leukemia virus cell receptor gene. AB - The missing 5'-end of the encoding region of the bovine leukemia virus (BLV) cell receptor gene (BLVRcp1/5') was isolated from a lambda gt11 cDNA library using the 32P-labeled EcoRI-SamI fragment corresponding to the 5'-end of a 2.3 kbp cDNA fragment encoding the binding domain of the bovine leukemia virus cell receptor gene (BLVRcp1). The nucleotide and amino acid sequence analysis of the BLVRcp1/5' cDNA revealed that the 1058 bp EcoRI fragment at its 5'-end contained a new 114 amino acid long sequence, and at its 3'-end contained a completely identical 88 amino acid overlapping region with the 5'-end of the BLVRcp1 cDNA. The combined sequences of both cDNAs represent the whole encoding region of the BLV cell receptor gene. The longest open reading frame of the BLV cell receptor gene encodes a protein containing 843 amino acids with a calculated molecular mass of 94.2 kDa which concurs with experimentally detected native BLV receptor protein. Search for homology has shown that about 250 bp of the BLV cell receptor gene is highly homologous to Venter's tag sequences of an unidentified gene from the human brain library. PMID- 7998844 TI - Detection of avocado sunblotch viroid in chloroplasts of avocado leaves by in situ hybridization. AB - In situ hybridization experiments were carried out to detect avocado sunblotch viroid (ASBVd) in foliar tissue of avocado, using a digoxigenin-labelled RNA probe complementary to the ASBVd-RNA in sections of aldehyde-fixed, LRGold embedded leaf samples. Detection of the probe was made through anti-digoxigenin antibody and protein-A colloidal gold (20 nm). Seventy to 80% of the signals came from chloroplast while the cytoplasm and vacuole were labelled with ca. 10% of the gold particles. This is in contrast with the subcellular localization of potato spindle tuber viroid and some other related viroids, which are mainly found in the nucleus. PMID- 7998846 TI - [Dobutamine pulse therapy in patients with severe heart failure. Is it a beneficial measure?]. PMID- 7998845 TI - Replication of human cytomegalovirus in a rhabdomyosarcoma cell line depends on the state of differentiation of the cells. AB - The replication of human cytomegalovirus (HCMV) was investigated in a new human rhabdomyosarcoma cell line (KFR) with morphological and biochemical characteristics of fetal striated muscle precursors (rhabdomyoblasts). KFR cells exhibited the unique property for spontaneous morphological transformation from a poorly-differentiated state into well-differentiated (myotube-like) rhabdomyoblasts. The poorly-differentiated rhabdomyoblasts promoted both complete viral gene expression and the production of infectious virus. In contrast, in well-differentiated rhabdomyoblasts HCMV infection was abortive. The results showed that replication of HCMV in this human rhabdomyosarcoma cell line depended on the state of cellular differentiation. PMID- 7998847 TI - [Percutaneous cardiovascular intervention procedures in Brazil (1992-1993). Report of the National Registry-National Center for Cardiovascular Interventions]. AB - PURPOSE: To report the data on the first 2 years (1992-1993) of activity of the National Registry of Cardiovascular Interventions (CENIC) of the Hemodynamic and Angiography Department (DHA) of the Brazilian Society of Cardiology (SBC). METHODS: The full members of the DHA of the SBC sent their data on seven types of interventions: balloon angioplasty (PTCA), mitral balloon valvoplasty (MBV), pulmonary balloon valvoplasty (PBV), aortic balloon valvoplasty (ABV), tricuspid balloon valvoplasty (TBV), aortic balloon dilation (AoB) and balloon dilation of pulmonary branches (PBB), to the CENIC. RESULTS: Ninety-seven interventional cardiologists and 71 hospitals in 14 states, participated in this data bank. During this time, 16,429 PTCA, 551 MBV, 347 PBV, 62 ABV, 61 AoB, 3 TBV and 3 PBB were registered. PTCA was therefore the most performed procedure (94%); primary success rate was 89.7%. As for the major complications, there were 2.5% acute myocardial infarction; 0.8% emergency bypass surgery and 1.8% death. As for the other interventions, the primary success rate was 92.9% for MBV, 88.5% for PBV, 80.3% for AoB, 72.6% for ABV, 66.7% for TBV with 0.54% deaths for MBV patients and 3.23% for ABV patients. CONCLUSION: The performance of the interventional cardiology in Brazil reflects the difusion of intervention methods in the main hospitals of the country. The results demonstrate a high efficacy and safety rate, characterizing an excellent performance. PMID- 7998848 TI - [Laser coronary angioplasty. Critical analysis of the first patients]. AB - PURPOSE: To evaluate the success rate and complications, as well as the technical difficulties involved catheter laser coronary angioplasty, making evident the unsuccessful cases. METHODS: Twenty eight patients were treated with laser from August to November, 1993. The treatment was complemented with balloon angioplasty. Lesions were complex: 10 (36%) were type B and 18 (64%), type C. Concerning the obstruction grade, 18 (64%) were > or = 95%. Laser generator CVX 300(TM) Spectranectics as well as Extreme(TM) and Vitesse(TM) catheters with 1.4, 1.7 and 2.0mm in diameter, concentric and excentric, were used. Laser procedure success was defined as a reduction > 20% in the obstruction grade. The procedure success was attended when the residual stenosis was < 50% after a 15-minute observation, after balloon complementation. RESULTS: The unsuccess rate with laser catheter (Lc) was 34% (10 lesions) of which 3 cases were solved by other methods, 5 were not successful because of anatomic difficulties in surpassing the lesion and, in the two others the success criterium in the reduction of the obstruction grade of the coronary artery was not achieved, although the lesion surpassing was possible with the use of balloon catheter. The final success reached 89% (21 lesions). The procedure complications were a case of thrombosis, a perforation accompanied by a myocardial infarction and another myocardial infarction (non-Q wave), all with good outcome. CONCLUSION: The use of laser in the treatment of coronary artery obstructive lesions is a viable method. Nonetheless, more experience is necessary to demonstrate its actual value, optimizate the results and may be reduce restenosis rate. PMID- 7998849 TI - [Dynamics of patient selection for heart transplantation or cardiomyoplasty]. AB - PURPOSE: To evaluate patient selection for heart transplantation or dynamic cardiomyoplasty. METHODS: We evaluated 380 patients from April 1991 to July 1993. The ages ranged between 16 and 68 (mean 43.5 +/- 11.46) years, 303 (79.7%) were male. The diagnoses were dilated cardiomyopathy in 163 (42.9%), Chagas' cardiomyopathy in 70 (18.4%), ischemic heart disease in 61 (16.1%), hypertensive heart disease in 40 (10.5%), valvular heart disease in 23 (6.1%), alcoholic cardiomyopathy in 12(3.2%), peripartum cardiomyopathy in 5 (1.3%) and myocarditis of unknown etiology in 5 (1.3%). RESULTS: The indication of heart transplantation was eventually done in 55 (14.4%), and 19 (5%) were submitted to transplantation. Dynamic cardiomyoplasty was indicated in 9 (2.3%) patients and was performed in 8 (2.1%). In 30 (7.8%) patients there were clinical contraindications for transplantation. Conventional surgical treatment was indicated for 12 (3.1%) patients: myocardial revascularization and/or ventricular aneurismectomy in 5, surgical treatment of valvular heart disease in 6 and of atrial fibrillation in 1. Socioeconomic limitations precluded transplantation in 43 (11.3%) and psychic limitations hindered transplantation in 23 (6.0%) patients. Refusal of procedure by the patient occurred in 10 (2.6%) cases. Improvement of the symptoms occurred in 69 (18.1%) patients. CONCLUSION: A small percentage of patients are eligible and are eventually submitted to heart transplantation or dynamic cardiomyoplasty. New strategies may be delineated during follow up, as deferring transplantation or conventional surgical treatment of ischemic or valvular heart disease. Sociopsychic evaluation is an important step in the care of the patients. PMID- 7998850 TI - [Functional anatomy of the junction of the left atrium and the pulmonary veins]. AB - PURPOSE: To study the spatial arrangement of the bundles of myocardial fibers presents in the left atrial-venous junctions and in the wall of the pulmonary veins. METHODS: The study was made on 24 human adult hearts, together with pulmonary vessels, fixed in 10% formaldehyde solution. Each specimen was cleared of remnants of pericardium to expose the myocardial fibers as clearly as possible. Particular attention was paid to the atrial-venous junction and the extension of the myocardial fibers in the pulmonary veins. The specimens were embedded in celloidin and cut serially at a thickness of 70 mu and stained by methods of Azan's trichrome. RESULTS: The myocardial bundles leave the atrial wall around the openings of all pulmonary veins forming a sphincter-like structure. These fibers are continuous in the adventitial coat running in oblique or spiral directions. Some bundles, more external, leaving from the atrial wall, surround the ostium of the veins and return to the atrium, forming true loops. CONCLUSION: The extremities of the pulmonary veins and their junctions with the atrium have a morphological substract which may be of physiological importance in the control of the pulmonary venous pressure and blood flow. PMID- 7998851 TI - [Infective endocarditis in patients with permanent pacemaker]. AB - Five patients who had permanent pacemaker and infective endocarditis were analyzed. Diagnose was confirmed by a positive blood cultures in all patients and 2 of them had identifiable vegetation in the echocardiogram too. The etiologic agent was Staphylococcus aureus in 3, Staphylococcus epidermidis in 1 and Staphylococcus viridans in 1. Three patients were treated with antibiotics alone: one had no clinical conditions to be operated, one died before surgery and one had good response to antimicrobial therapy alone. Two patients were submitted to antibiotic therapy and surgical removal of the pacemaker system, without complications. It was concluded that the surgical removal of the pacemaker system, as soon as possible, is the choice's therapy. PMID- 7998852 TI - [Thromboembolism of the right coronary after ventricular tachycardia with inferior wall myocardial infarction and normal coronary arteries and intracavitary thrombus]. AB - A 47 year-old man, with signals of low cardiac output due to sustained ventricular tachycardia, without history of pain. After clinical control of the arrhythmia, he was underwent to coronary-angiography that showed no obstructive lesion, but a thrombus was present in the distal right coronary artery. There was hypocinesia of the inferior wall of the left ventricle and the presence of a mural thrombus in that region. The patient was kept under clinical treatment and sent back to his cardiologist. PMID- 7998853 TI - [Reversal of left ventricular hypertrophy after the use of benazepril]. AB - PURPOSE: To assess the effects of benazepril (ACE inhibitor) on arterial blood pressure (ABP) and left ventricular mass index (LVMI). METHODS: Nineteen patients (7 men, 12 women) with mean age 38.2 +/- 10.2 years, with mild to moderate hypertension were evaluated. Besides raised blood pressure, the necessary inclusion criterion was the presence of left ventricular hypertrophy detected by echocardiogram. After a wash-out period, all patients were given placebo followed by the active drug benazepril at a dose of 10 mg once a day. For those patients who did not achieve a satisfactory control of the blood pressure (BP) 25 mg of chlorthalidone was added. All patients underwent 180 days of benazepril treatment. RESULTS: The ABP was gradually controlled as follow: at seated position the systolic BP changed from 156.05 +/- 5.07 mmHg to 129 +/- 3.74 mmHg (p < 0.001) and the diastolic BP from 99.74 +/- 1.59 mmHg to 81.8 +/- 2.27 mmHg (p < 0.001). At orthostatic position the systolic BP changed from 156.9 +/- 5.35 mmHg to 124.28 +/- 5.33 mmHg (p < 0.001) and the diastolic BP from 101.7 +/- 1.34 to 81.36 +/- 2.81 (p < 0.001). The heart rate did not change significantly during the study. The LVMI decreased significantly from 182.4 +/- 9.2g/m2 to 122.6 +/- 4.2g/m2 (p < 0.001). CONCLUSION: Our data revealed that 100% of the patients achieved satisfactory degrees of LVMI regression and in 34% there was a normalization of it. PMID- 7998854 TI - [Importance of the endothelium in coronary heart disease and atherogenesis]. PMID- 7998855 TI - [Why a myogenic theory and not a thrombogenic theory?]. PMID- 7998856 TI - [Cardioplegia: exegesis]. PMID- 7998857 TI - [Endomyocardial biopsy and immunosuppressive therapy in patients with myocarditis]. PMID- 7998858 TI - [The dilemma of myocarditis treatment]. PMID- 7998859 TI - [What priority: low or high cardiovascular risk? A scientific homage to Geoffrey Rose]. PMID- 7998860 TI - [Reproducibility of head-up tilt test in patients with neurocardiogenic syncope]. AB - PURPOSE: In order to identify the reproducibility of head-up tilt test, a second test one week later in 22 patients with a positive first test, was performed. METHODS: The test was performed in a fasting state during the morning. The heart rate and blood pressure were monitored during 20 minutes in the supine position and then at 60 degrees for up to 40 minutes. The test were considered positive if the patient experienced syncope or pre-syncope with fall in systolic blood pressure > 30mmHg. The following aspects were evaluated: reproducibility of the positive response; the type of response (hypotension, asystole or hypotension plus bradycardia) and the time interval between tilt and the beginning of symptoms. RESULTS: Eighteen (82%) patients had a second positive response; 14 (77.8%) of then had the same type of response; and 17 (94%) had syncope in similar time interval after tilt. CONCLUSION: The head-up tilt testing has good reproducibility, although its use in the therapeutic management needs a longer period of evaluation. PMID- 7998862 TI - [Tetralogy of Fallot: considerations about morphologic features of a well described entity]. AB - PURPOSE: To analyze some morphological aspects of the tetralogy of Fallot which have been raising controversies in the literature, due to the different approach to the nomenclature of congenital heart defects by different authors regarding the definition of double outlet right ventricle and its concomitance with tetralogy. METHODS: We reviewed the original description of the anomaly, and also analyzed the morphology of 22 anatomical specimens, describing the degree of aortic overriding, the type of ventricular septal defect, the degree of sub pulmonary stenosis, etc. RESULTS: Regarding the degree of aortic overriding, there was only one case where that vessel connected predominantly to the left ventricle. In the remaining hearts, the degree of overriding was between 50% and 75% in 10 cases and greater than 75% in 11. The intensity of infundibular stenosis was evaluated as mild in half the available hearts, and the pulmonary valve was bicuspid in 11 cases. Right aortic arch was present in 40% of the available hearts and the ventricular septal defect had muscular borders in just one case (5%). CONCLUSION: We could conclude that if double outlet is only a type of ventricle-arterial connexion, and so, depending on the degree of overriding of the aorta over the trabecular septum, we may have the malformation coexisting with the tetralogy. PMID- 7998861 TI - [Arrhythmias following orthotopic heart transplantation]. AB - PURPOSE: To correlate the incidence of arrhythmias to the degree of allograft rejection on endomyocardial biopsy. METHODS: Seventeen patients who underwent orthotopic heart transplantation were submitted to ambulatory Holter monitoring 24h prior to endomyocardial biopsy. The biopsy results were compared to Holter monitoring results. RESULTS: The mean study period was 252 +/- 166 days (15 to 515). We found a high incidence of ventricular premature beats (> 70%), except in patients with severe rejection (25%), but there was no statistically significant difference between the groups with no rejection, mild and moderate rejection. Atrial premature beats were more common in patients with mild and moderate rejection (53% and 70%, respectively) when compared to patients with no rejection (33%) and patients with severe rejection (9%), (p < 0.05). Sinus bradycardia was present in 50% of patients with severe rejection, but only in 9% of moderate, 3% of mild and 5% of the patients with no rejection (p < 0.05). CONCLUSION: Supraventricular tachycardia and atrial premature beats are related to moderate rejection. Ventricular premature beats are not related to degree of rejection. Sinus bradycardia occurring in the first year after transplantation should suggest severe cardiac allograft rejection. PMID- 7998863 TI - [Hypertension and complex ventricular arrhythmias. Evolution following a long term blood pressure treatment]. AB - PURPOSE: To evaluate the effects of long-term antihypertensive treatment in the frequency as well as in the complexity of ventricular arrhythmias in arterial hypertension. METHODS: Twenty three patients, 14 males and 11 whites, with mean age of 46 years, were submitted to 24 hours ambulatory electrocardiographic monitoring and echocardiographic studies before and 9 months after antihypertensive treatment. RESULTS: There was no significant serum potassium level alteration, but significant reductions of both systolic (from 192 +/- 29mmHg to 161 +/- 25mmHg) and diastolic (from 122 +/- 17mmHg to 99 +/- 16mmHg) blood pressure. Left ventricular percent of fiber shortening significantly increased, even though only from 26 +/- 9% to 30 +/- 9%, and end-systolic wall stress did not change at all (before 258 +/- 94 10(3) dyn/cm2, after 255 +/- 101 10(3) dyn/cm2). Left ventricular mass index showed significant but also a discrete reduction from 211 +/- 75g/m2 to 196 +/- 70g/m2. Ambulatory electrocardiographic monitoring did not show any significant decrease in neither ventricular ectopic beats nor in couplets. Non-sustained ventricular tachycardia episodes remained unchanged too. Four out of 8 patients with more than 30 ventricular ectopic beats per hour reduced it by more than 70%. On the other hand, the number of patients with couplets was reduced from 10 to 8 whilst those with non-sustained ventricular tachycardia increased from 5 to 7. Furthermore, in 7 patients reevaluated 24 months thereafter results were not expressively dissimilar. CONCLUSION: In hypertensive patients with either severe degree of left ventricular hypertrophy or myocardial dysfunction, long-term blood pressure treatment that produce no impressive changes in these abnormalities also do not modify complex ventricular arrhythmias, in spite of a great reduction in the increase blood pressure. PMID- 7998864 TI - [Clinical and hemodynamic aspects of non-obstructive coronary lesions. A comparative retrospective study]. AB - PURPOSE: To study the clinical and hemodynamic aspects of a group of patient presenting non-obstructive coronary lesions. METHODS: We reviewed 963 coronary angiographies performed at a same institution. The 52 patients presenting only stenosis < or = 50% after semi-quantitative measurement composed group I, which was compared with two other groups consisted of 52 patients each: one, with patients presenting univascular lesion > 50% (group II) and the other with normal coronary arteriographies (group III). RESULTS: Mean age was similar in groups I and II (49.4 +/- 6.89 and 51.3 +/- 7.86, p > 0.05) and significantly higher than that of group III (44.8 +/- 6.81, p < 0.05). Risk factors did not discriminate group I (GI) from groups II (GII) and III (GIII). During a follow-up period of 63 months, the number of hospital admissions due to cardiac events and repetitions of coronary arteriography were similar in GI and GII, being significantly less frequent in GIII (p < 0.00001 and 0.001; p < 0.01 and 0.05, respectively). By the end of the follow-up period, though angina and heart failure functional classes had been similar in the three groups, patients in groups I and II were using more medications than those in group III (p < 0.0001 and 0.00001). Mean ejection fractions (%) were lower in GI and GII (67.04 +/- 10.13 and 68.90 +/- 11.32) than in GIII (74.69 +/- 6.40, p < 0.01). Lesions were predominantly proximal in GI when compared with GII (p < 0.05). Length, simmetry, ulceration, thrombus and proximal shoulder showed no difference between GI and GII. CONCLUSION: Patients with non-obstructive coronary lesions were similar to those with univascular lesion > 50% regarding several aspects and were considerably different from those with normal coronary arteries. PMID- 7998866 TI - [Influence of atrial fibrillation in the natural history of hypertrophic cardiomyopathy]. AB - PURPOSE: To evaluate the influence of atrial fibrillation in the natural history of hypertrophic cardiomyopathy. METHODS: Eighty-eight patients under ambulatory treatment were studied. Most of them presented the asymmetric type of hypertrophic cardiomyopathy (87.5%). Group I (77 cases) was formed by patients who had never had atrial fibrillation and group II (11 cases) by those who had this arrhythmia paroxysmal or established. RESULTS: In group I, with ages 48.02 +/- 14.82 years, left atrial dimensions 4.21 +/- 0.66 cm, there was one sudden death; 69 were treated by clinical means and 7 by surgery; no patient developed thromboembolism neither cardiac failure. In group II, with ages 58.02 +/- 11.04 years and left atrial dimension 5.32 +/- 0.45 cm, there were 4 deaths, 4 thromboembolisms and 3 with cardiac failure; all received only clinical treatment, having improved in clinical status in 71.42% after amiodarone therapy. CONCLUSION: Atrial fibrillation was present in 12.5%, mostly in the asymmetric type, and in patients after 5th decade, all of them with enlarged left atrium (> 4.7 cm), with highest morbidity (thromboembolism and cardiac failure) and mortality. Among the survivors, amiodarone therapy improved functional class in 71.42%. PMID- 7998868 TI - [Sinus bradycardia with junctional rhythm escape reverted with calcium gluconate]. AB - A 65-years-old female patient in chronic use of verapamil who developed bradyarrhythmia and hypotension reverted by endovenous calcium gluconate. PMID- 7998865 TI - [Ischemic mitral valve insufficiency. Incidence, diagnosis and surgical treatment]. AB - PURPOSE: To study the incidence of ischemic mitral regurgitation (MR) and the mortality. METHODS: One-hundred-five cases of acute myocardial infarction (AMI) with MR were reviewed. Patients were divided in two groups: group A-59 (56.2%) necropsied patients without previous surgical procedures to correlate clinical pictures with the aim to determine the cause of death; group B-46 (43.8%) patients were submitted to surgical treatment. This group was subdivided in mild, moderate and severe forms of MR, and studied comparatively the type of surgical treatment and its evolution. RESULTS: Group A-23 (39%) patients with mild forms and predominant ischemic heart disease, responsible for death; 18 (30.5%) patients without previous diagnosis, masked by myocardial failure and 18 (30.5%) with severe MR and coronary heart disease; group B-14 (30.4%) patients died at the immediate post-operatory period. Higher mortality associated to ejection fraction (EF) below 35% (47.6%; p = 0.022), severe MR (41.7%; p = 0.044) and cardiogenic shock (52.9%; p = 0.14). In 41 (89.1%), the mitral valve repair was combined to coronary artery bypass grafting operation (CABG), in 4 (8.7%) this last procedure was made without mitral repair and in the remaining patients the surgery was limited to the valve. Mitral valvuloplasty was performed in 23 (50%) patients with 3 (13%) deaths, and in 19 (42.3%) the mitral valve was replaced with 9 (47.4%) deaths. CONCLUSION: The prognosis is related to the grade of EF and to the severity of MR. In mild to moderate forms, the surgical indication is due to the associated coronary heart disease and the valvuloplasty is preferred, in this instance. In severe forms, surgical intervention must be performed as soon as possible, before cardiogenic shock appears. PMID- 7998869 TI - [Case 3/94 (Instituto do Coracao do Hospital das Clinicas-FMUSP) Dilated cardiomyopathy]. PMID- 7998867 TI - [Coronary angioplasty in chronic occlusion of 9 and half years. Use of laser with a new catheter for recanalization]. AB - A chronic total occlusion lasting 9.5 years, was successfully treated with a Prima (TN) Laser catheter, of Spectranectics. The authors report a case of a fifty seven year old male that suffered an inferior myocardial infarction 9.5 years ago. Although the morphological characteristics of the lesion seemed easy to pass through the obstruction with the guide wire, the balloon dilatation was not possible because of the hardness of a chronic lesion lasting that long. The intervention was concluded successfully in another opportunity using the laser catheter with certain facility. This case, reported as the first one in Latin America, rises new possibilities and increases the success rate of coronary angioplasty of total chronic occlusions. We hope that in the following cases we will be able to reach the same result, widening the indications of coronary angioplasty. PMID- 7998870 TI - [Evaluation of the mechanic performance of the heart using isolated papillary muscles. Critical analysis of the method]. PMID- 7998872 TI - Inaugural Midwifery Education Conference. PMID- 7998871 TI - [Treatment of mild and moderate hypertension with fosinopril. Comparison of adverse effects with other antihypertensive agents]. AB - PURPOSE: To evaluate the adverse reactions of fosinopril with other antihypertensives used as monotherapy. METHODS: Out-patients (n = 2,568) with diagnostic of mild to moderate hypertension, diastolic blood pressure (DBP) 95 115mmHg, with no antihypertensive treatment for 15 days, were included to treatment initially with fosinopril (F) 10mg, once daily, for six weeks. After this period, patients with DBP > 95mmHg had the dosage, once daily, increased to 20mg, while the others were maintained with the same dosage for six more weeks. Adverse reactions of 822 patients treated as monotherapy were grouped as absent, musculoskeletal, cardiovascular, cough, gastrointestinal, neurological, genital urinary dysfunctions and dermatological and compared with 1,568 with F. Monotherapy consist in alpha-methyldopa (100 patients); beta-blocker (129); calcium blocker (106); diuretic (394); and another ACE inhibitors (93). RESULTS: At the end of the period without treatment, the blood pressure (BP), 165 +/- 16/105 +/- 7mmHg decreased significantly at 6th week to 144 +/- 15/91 +/- 9mmHg (p < 0.05 vs week 0) with further lowering to 139 +/- 13/86 +/- 7mmHg till the end of 12th week. BP response (DBP < or = 90mmHg) was obtained in 89% of the patients with F. Absence of adverse reactions were > or = 70% in patients with F compared to other drugs. CONCLUSION: Fosinopril has demonstrated therapeutic efficacy and less adverse reactions compared to antihypertensives used previously as monotherapy. PMID- 7998874 TI - The clinical guest: the role of the academic in the clinical agency. PMID- 7998873 TI - Preparing the midwife of the future: using a distance education model to extend our teaching boundaries. PMID- 7998875 TI - Rural community safe motherhood in Cambodia. PMID- 7998876 TI - Rhythmical fluctuation of arterial pressure after implantation of cardiac prosthesis. PMID- 7998877 TI - Carotid arterial impedance during oscillated blood flow. AB - Blood perfusion of systemic circulation is influenced by the physical characteristics of artery. Several investigations proposed that the physical parameters of vessels are determined by neurological factors, hormonal factors, and physical properties of arteries among others. In this study, arterial impedance was estimated because it may express the condition of vessels. To examine the change of arterial impedance according to the blood flow pattern, the typical sine wave blood flow (oscillated flow) was used during total cardiopulmonary bypass (CPB) because it is considered the most simple pulsatile flow. CPB using oscillated blood flow was performed in acute experiments on adult goats. Total systemic flow was controlled to remain at approximately 80 ml/min. Carotid arterial flow, aortic pressure, central venous pressure, and systemic flow were measured. Total peripheral resistance, carotid arterial resistance, systemic impedance, and carotid arterial impedance were calculated to evaluate blood flow distribution during CPB. This study suggested that the parameters of carotid arterial blood flow changed according to the change of flow frequency during oscillated blood flow. This change may occur because arterial impedance was influenced by flow frequency; therefore, the blood flow of the carotid artery was significantly changed according to the change of the frequency component of blood flow. PMID- 7998878 TI - Chaotic hemodynamic during oscillated blood flow. AB - A vibrating flow pump (VFP), which can generate oscillated blood flow (10-50 Hz/min), has been developed by our team for the artificial heart system. However, the flow pattern of this pump was different from that of the natural heart; therefore, it is important to analyze the effect of this oscillated blood flow on the circulatory regulatory system. To analyze the hemodynamics of high frequency oscillated blood flow as an entity, (not decomposed), nonlinear mathematical techniques were utilized. VFPs were implanted between the left atrium in animal experiments using adult goats. After the implantation procedure, the ascending aorta was clamped to constitute the complete left heart circulation with VFP. Using a nonlinear mathematical technique, an arterial blood pressure waveform was embedded into four-dimensional phase space and projected into three-dimensional phase space. The Lyapunov numerical method was used as an adjunct to graphic analysis of the state space. Phase portrait of the attractor showed a high dimension complex structure, suggesting deterministic chaos during natural circulation. However, phase portrait of the hemodynamics during oscillated blood flow showed a single circle with banding and a forbidden zone, similar to a limit cycle attractor, suggesting a lower dimensional dynamic system. Positive Lyapunov exponent during oscillated blood flow suggests the existence of lower dimensional chaotic dynamics. These results suggest that the circulatory regulatory system during oscillated blood flow may be a lower dimensional homeochaotic state; thus, hemodynamic parameters must be carefully regulated when unexpected external stimuli are present. PMID- 7998879 TI - Do we really need pulse? Chronic nonpulsatile and pulsatile blood flow: from the exercise response viewpoints. AB - The response of the body and the blood pump was evaluated in animals with a pulsatile artificial heart (total artificial heart [TAH]) and those with a nonpulsatile artificial heart (nonpulsatile biventricular bypass [NPBVB]) subjected to the same exercise load. The animals used in this study were 5 calves implanted with a pusher-plate type TAH (45-206 days) and 5 calves implanted with a nonpulsatile centrifugal pump (34-99 days). The pre-exercise pump flow rate was 92.1 +/- 8.1 ml/kg/min for the TAH group and 94.8 +/- 9.1 ml/kg/min for the NPBVB group, with no significant difference between the two groups. The workload was administered at a rate of 1.5 mph for 15 min. The artificial heart driving conditions were kept constant throughout the test period. Sequential changes in hemodynamic response and metabolism were determined before, during, and for 30 min after exercise. Both TAH and NPBVB calves showed excellent tolerance of the workload (1.5 mph exercise); in NPBVB calves, oxygen demand was compensated for by an increase in the arteriovenous oxygen difference during exercise; and norepinephrine showed a greater response in the NPBVB group. Based on the results presented, the nonpulsatile pump seems to lend itself to a mechanically driven artificial heart of the complete implantation type because of its small size, high efficiency, and the lack of need for a compliance chamber. PMID- 7998880 TI - Pulsatile flow and simple flow control method during weaning period in centrifugal pump: toward more expanded usage in open heart surgery. AB - To expand the usage of the centrifugal pump (CP) in open heart surgery, we performed two studies. In the first, we evaluated pulsatile flow in the CP. In vitro pump performance of the Terumo Capiox pump (TCP) and the Sarns Delphin pump (SDP) and increase of free hemoglobin (mg/dl) after driving 6 h were investigated using bovine blood. A roller pump (RP) was used as a comparison. Equally effective pulsatile flow was obtained in both CPs. Hemolysis was less severe in TCP (120 mg/dl) than SDP (210 mg/dl) and RP (320 mg/dl). In the second study, we evaluated a simple flow control method. Flow rate was easily controlled with step wise clamping of 3-pronged tubing (Triple-flow) without changing rotational speed, regardless of afterload. Fluctuation of flow was much less with this method than with the rotational speed change method. The use of pulsatile flow of TCP, with its minimum increase of hemolysis and the easier flow control method during the weaning process, may expand the usage of CP in open heart surgery. PMID- 7998881 TI - Does hematocrit affect in vitro hemolysis test results? Preliminary study with Baylor/NASA prototype axial flow pump. AB - The effect of hematocrit (Ht) on in vitro hemolysis test results (i.e., index of hemolysis) was evaluated using a Baylor/NASA prototype axial flow pump. Red blood cell suspensions of six different Ht (5, 10, 15, 20, 30, 40%; n = 30) were prepared and used for this evaluation. The pump was operated for 60 min under 5 L/min flow conditions, and blood samples were taken every 10 min to measure plasma free hemoglobin levels. The normalized index of hemolysis (NIH) was calculated using the regression line slope between time and plasma free hemoglobin level, and relationships between NIH and Ht or hemoglobin (Hb) were checked. NIH and Ht had a statistically significant (p < 0.0001) correlation with a coefficient of fit of 0.976, and NIH and Hb had a statistically significant (p < 0.0001) correlation with a coefficient of fit of 0.976. To reduce the effect of Ht, NIH/Ht was proposed and compared with a modified index of hemolysis (MIH), which was normalized by the Hb level of blood. NIH/Ht and MIH had a poor correlation with Ht (coefficient of fit, 0.608) and Hb (coefficient of fit, 0.577), respectively. When blood that has a wide range of Ht or Hb values is used for in vitro hemolysis tests, NIH/Ht is suggested for use as an index of hemolysis to evaluate the hemolysis characteristics of rotary blood pumps because MIH has no dimension and it requires Hb values. In contrast, NIH/Ht has a dimension of g/100 L, which is quite understandable, and it does not require measurement of Hb levels of blood; it is therefore cost-effective. PMID- 7998882 TI - Concept designs of nonrotating-type centrifugal blood pump and basic study on output characteristics of the oscillating disk-type centrifugal pump. AB - When designing a turbo-type blood pump as an artificial heart, the gap between a rotating shaft and a pump housing should be perfectly sealed to prevent any leakage or contamination through a seal. In addition, blood coagulation in a blood chamber must be avoided. To overcome these problems, we proposed five different nonrotating-type turbo pumps: a caudal-fin-type axial-flow pump, a caudal-fin-type centrifugal pump, a nutating-column-type centrifugal pump, a nutating-collapsible-tube-type centrifugal pump, and an oscillating-disk-type centrifugal pump. We selected and developed the oscillating-disk-type centrifugal pump that consists of a disk, a driving rod, a seal, an oscillation mechanism, and a pump housing. The disk is mounted on the end of the rod, which is connected to a high-speed DC motor through an oscillation mechanism. The rod and the disk do not rotate, but they oscillate in the pump housing. This movement of the disk generates forward fluid flow around the axis (i.e., the rotational fluid flow). Centrifugal force due to fluid rotation supports the pressure difference between the outlet and the inlet. The diameter of the disk is 39 mm, the maximum inner diameter of the pump housing is 40 mm, and the volume of the blood chamber for 25 degrees' oscillation is 16.9 ml. The performance of the pump was tested in a mock circulatory system.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7998883 TI - A miniaturized centrifugal pump for assist circulation. AB - The newly developed Nikkiso HMS-15 is a miniaturized centrifugal pump. It has an impeller diameter of only 50 mm and a priming volume of only 25 ml. A totally new approach was applied to develop this very small pump. The new pump showed comparable hemolysis with pumps twice as big (e.g., the most widely used cone shaped centrifugal pump [index of hemolysis, 0.005]). This finding refutes the belief that the pump diameter must be sufficiently large in size. Clinical application for cardiac assist was performed for 48 h without any thrombus formation despite low heparin dosage. Also, the pump showed quite favorable blood trauma when applied as a pump for cardiopulmonary bypass during open heart surgery. The compactness, the high controllability, and the system versatility proved to be very effective for clinical application. This pump is considered very reliable for its highly optimized design. PMID- 7998884 TI - A flow visualization study of the NCVC centrifugal blood pump. AB - A compact centrifugal pump, NCVC-1, has an open-type impeller with 6 curved vanes, and it is characterized by no shaft and no seal. A tunnel is placed in the center of the impeller-rotor assembly to irrigate the back space behind the rotor. To evaluate the flow, we performed 3 visualization methods: tracer, oil film, and injection streak line method. The flow, observed by the tracer method in NCVC-1, indicated little turbulence along vanes. A volute chamber proved effective to reduce vortex formation in the outlet. Oil film pattern revealed no flow separation on vanes at 5 L/min. Washout flow behind the rotor is essential to prevent thrombus formation and was shown as inward spiral flow without any stagnation. These data suggested that a combination of visualization techniques was useful to analyze various flow conditions, and the NCVC-1 has excellent flow characteristics with little turbulence and little flow stagnation, which must be beneficial to low hemolysis and high antithrombogenicity. PMID- 7998885 TI - Development and evaluation of antithrombogenic centrifugal pump: the Baylor C Gyro Pump Eccentric Inlet Port Model. AB - The Baylor C-Gyro Pump Eccentric Inlet Port Models (C1E) have been developed aiming for a long-term centrifugal ventricular assist device (VAD) as well as a cardiopulmonary bypass pump. The eccentric inlet port models are characterized by their unique inlet port and secondary impeller vanes. An inlet female pivot bearing, which was fixed to a supporting bar in the prototype model, is directly embedded into the ceiling of the pump casing. An inlet port is then placed off center to avoid the bearing area, and it is angled between 0 to 90 degrees from the upright position. In addition, small secondary vanes were incorporated into the impeller bottom to accelerate the washout flow behind the impeller. These features attained design objectives proposed for higher antithrombogenicity: a seal-less pump chamber, no stationary parts in the blood path, and acceleration of the secondary flow behind the impeller. The first in vivo experiment using C1E pumps showed excellent antithrombogenicity for up to 18 days when the experiment ceased due to severe infection in the calf. PMID- 7998886 TI - The margin of safety in the use of a straight path centrifugal blood pump. AB - A new centrifugal blood pump with a rotor that arranges 6 straight paths radially was developed for open heart surgery and temporary circulatory support. We describe comparative studies of the margin of safety in the practical use of the new pump. This pump was evaluated for temperature increase, cavitation, and pressure sensitivity. Two commercially available centrifugal pumps, the Biomedicus cone type and the Sarns 3M impeller type, were used as control pumps. The temperature increase in the new pump was four times slower than in the impeller pump when the outlet and the inlet of the pump was clamped. No sign of cavitation was observed when 0.1 ml air was introduced to the pump inlet under a negative pressure of 200 mm Hg in fresh bovine blood. As for pressure sensitivity of centrifugal pumps in practical applications, circuit resistance was a more essential factor than flow-pressure curves of the pump. PMID- 7998887 TI - Less platelet damage in the curved vane centrifugal pump: a comparative study with the roller pump in open heart surgery. AB - The centrifugal pump with the curved vane (Lifestream Centrifugal Pump [LCP]) was applied to cardiopulmonary bypass (CPB) in 10 patients who underwent elective coronary artery bypass grafting. Serum hemoglobin levels, platelet counts, and serum beta-thromboglogulin (beta-TG) levels were measured during CPB. The results were compared with those for a comparative roller pump (RP) group (n = 10). There was no difference in CPB time between LCP (112 +/- 22 min) and RP (121 +/- 22 min) groups. Serum beta-TG levels (ng/ml) were lower in the LCP group than in the RP group (34 +/- 9 vs. 101 +/- 80, 5 min; 81 +/- 33 vs. 236 +/- 112, 30 min; 120 +/- 53 vs. 314 +/- 100, 60 min after initiation of CPB; p < 0.05). There were no significant differences in hemolysis and platelet depletion. The LCP showed excellent hemodynamic performance with less blood trauma in clinical application to open heart surgery. PMID- 7998888 TI - Results of circulatory support for postoperative cardiogenic shock. AB - Over the last 5 years, 15 patients received ventricular assist devices (VADs) (Group 1) and 5 received percutaneous cardiopulmonary support (CPS) (Group 2) while in postoperative cardiogenic shock. Group 1 consisted of 8 men and 7 women ranging in age from 22 to 73 years (average age, 55 years). Nine of these patients underwent surgery for valve replacement, 5 for coronary artery bypass grafting, and 1 for closure of a ventricular septal rupture. The duration of VAD support ranged from 6 h to 9 days (mean, 3.9 days). Group 2 consisted of 4 men and 1 woman ranging in age from 49 to 68 years (average age, 57 years). One of these patients underwent surgery for valve replacement, 1 for coronary artery bypass grafting, 2 for replacement of a thoracic aneurysm, and 1 for left ventricular aneurysmectomy. The duration of CPS ranged from 4 h to 8 days (mean, 2.8 days). In Group 1, 13 patients were weaned from the VADs and 8 survived. Bleeding occurred in 5 patients, renal failure in 4, infection in 3, cardiac failure in 4, cerebral infarction in 1, perioperative myocardial infarction in 1, arrhythmia in 1, and ileus in 1. In Group 2, 4 patients were weaned from the CPS and 3 survived. Bleeding occurred in 3 patients, renal failure in 2, CNS injury in 2, and cardiopulmonary failure in 1. The 8 survivors in Group 1 have been followed for 2 to 56 months (mean, 28.7 months). Five patients were in NYHA class I, 2 were in class II and 1 was in class III.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7998889 TI - Emergency cardiopulmonary bypass support in patients with cardiac arrest caused by myocardial infarction. AB - Emergency percutaneous cardiopulmonary bypass support (PCPS) was instituted in 3 patients with acute myocardial infarction in cardiac arrest refractory to conventional resuscitation measures. All had severe double or triple vessel disease. Percutaneous transluminal coronary angioplasty (PTCA) was performed in 1 patient and PTCA and directional coronary atherectomy (DCA) were performed in the other 2 patients on combined intraaortic balloon pumping (IABP) and PCPS. Flow rates of 2 to 5 L/min were achieved, with restoration of mean arterial pressure to more than 60 mm Hg during PCPS. The status of all patients was improved hemodynamically with PCPS. One patient died of hemorrhage during PCPS. DCA was successfully performed in the other 2 patients, and PCPS and IABP was discontinued. Time on PCPS ranged from 10 h to 8 days. Time on IABP ranged from 10 days to 2 weeks. These 2 patients died of pneumonia or multiorgan failure after 1.5 months. In conclusion, emergency PCPS is a powerful resuscitative tool that may stabilize the condition of patients in cardiac arrest to allow for definitive intervention. PMID- 7998890 TI - Clinical evaluation of a new type of centrifugal pump. AB - The major problems with existing centrifugal pumps are leakage, mechanical trauma, and thrombus formation. In consideration of these problems, a new compact centrifugal pump system was developed. The purpose of this study was to evaluate the new centrifugal pump system clinically. Ten patients underwent open heart surgery with a centrifugal pump or a roller pump. During surgery, hemodynamic and hematological data were obtained. A pulsatile assist device in the pump circuit was used in patients with severe heart disease. There was neither operative death nor hospital mortality, and there was no difference with regard to hemodynamic data between the two groups. The centrifugal pump groups, however, had significantly lower hemolysis, especially during prolonged cardiopulmonary bypass. This centrifugal pump could also create sufficient pulsatile flow with a pulsatile assist device. Postoperative macroscopic and microscopic findings demonstrated the smooth surface of the pump without thrombus formation. This centrifugal pump system might be useful for prolonged cardiopulmonary bypass. PMID- 7998892 TI - Code of regulations of the International Society for Rotary Blood Pumps (ISRP). PMID- 7998891 TI - Clinical experience with Nikkiso centrifugal pumps for extracorporeal circulation. AB - A comparative study of a newly developed impeller-type centrifugal pump, Nikkiso HMS-15, was made to assess the effects on hemolysis, platelet function, and renal function for extracorporeal circulation (ECC) during open heart surgery. The Bio pump (cone-type, Medtronic) and the roller pump were used as controls. The increase of serum hemoglobin level in the Nikkiso pump was significantly lower than that in the other pumps. The decrease of platelet counts was recognized after the initiation of ECC in the three pumps whereas the levels of platelet factor 4 and beta-thromboglobulin in the Nikkiso pump group increased by far less than in the other two groups. Moreover, renal function was better maintained in the Nikkiso pump group; in particular, a significantly higher urine output was recorded during ECC and for 1 h after the termination of ECC. The results of our clinical studies suggest that the Nikkiso centrifugal pump is suitable for ECC during open heart surgery. PMID- 7998894 TI - Cyclosporine, azathioprine and local therapy for pyoderma gangrenosum. AB - A markedly obese 54 year old woman with seropositive rheumatoid arthritis, anaemia, dyspepsia, controlled hypothyroidism and depression presented with a seven month history of large pyoderma gangrenosum ulcers on the shins. Routine dressings for the ulcers had been ineffective. Her arthritis was being treated with azathioprine and NSAID's. Initial treatment with clobestasol propionate and disodium cromoglycate under occlusion produced only partial healing. Introduction of Cyclosporin A and continuation of topical therapy, with the addition of triamcinolone acetonide injections, led to progressive healing which was complete after seven months. There has been no relapse to date. Cyclosporine can be combined with azathioprine and local therapy for successful treatment of pyoderma gangrenosum. PMID- 7998893 TI - Topical tretinoin improves the appearance of photo damaged skin. AB - A multicentre clinical trial has been conducted to assess the efficacy and safety of tretinoin 0.05% cream (Retin-A) in the treatment of photo-damaged Australian skin. Subjects with cutaneous facial photodamage were randomised to treatment with tretinoin (62) or vehicle (63) cream. After an initial two week run-in, all subjects applied the cream to the face, neck and left forearm/hand, once nightly for 24 weeks. Changes in clinical signs of photodamage and parameters of cutaneous irritation were assessed by investigators using a 7 point scale, whilst changes in signs of photodamage were rated by subjects using a 5 point scale. Changes in skin biopsies and silicone skin surface replicas were also assessed. Significant improvements in skin wrinkles, mottled hyperpigmentation, laxity, lentigines and roughness of tretinoin treated subjects were noted by investigators. Subjects receiving tretinoin noted significant improvements in skin wrinkles, tightness, colour and pores. Improvement in overall severity of photodamage was significantly greater for tretinoin treated subjects and was progressive over the study period. Histological findings included a significant increase in mean epidermal thickness. Significant topographical changes were not detected in skin surface replica sets. Cutaneous irritation, the most common side effect, was usually mild and transient. We conclude that tretinoin 0.05% cream significantly improved the appearance of photo-damaged skin. PMID- 7998895 TI - Adams-Oliver syndrome: aplasia cutis congenita, terminal transverse limb defects and cutis marmorata telangiectatica congenita. AB - A male infant with the features of Adams-Oliver syndrome is described. These features included severe aplasia cutis congenita (ACC) of the scalp involving both skin and cranium, a shortened right foot with talipes equinovarus, extensive cutis marmorata telangiectatica congenita and also haemangiomas and ulceration of the abdominal skin. Exposure of the dural membrane was associated with infection, hyponatraemia and finally localised necrosis with herniation of brain and fatal cerebral haemorrhage. PMID- 7998896 TI - An unusual presentation of secondary syphilis in the Northern Territory. AB - OBJECTIVE: To present a case which demonstrates the unusual clinical features of secondary syphilis that may be encountered in tropical Australia. CLINICAL FEATURES: A syphilitic aetiology was initially missed in a Caucasian female presenting with a rare form of syphilis, "lues maligna", characterised by nodulo ulcerative skin lesions, fever, meningism and a relapsing course. CONCLUSION: Secondary syphilis is usually manifest in the Northern Territory by a characteristic palmo-plantar psoriasiform eruption with variable involvement of skin in other body areas. The disease is most commonly seen in the young adult Aboriginal population. However, atypical presentations can occur and vigilance must be maintained for a syphilitic aetiology in unusual skin lesions. The disease may produce significant individual morbidity and may be transmitted non venereally to close contacts in the secondary stage. Genital lesions facilitate the transmission of HIV, making early diagnosis and treatment even more important. PMID- 7998897 TI - The clinical use of alpha hydroxy acids. AB - Alpha Hydroxy Acids are a group of organic acids which have recently become popular in the treatment of several skin conditions. This article explores some of the clinical uses of these products in the treatment of ichthyosis, acne, hyperpigmentation and photo-damage. Specific recommendations are given for the treatment of each condition. PMID- 7998898 TI - Proteolytic enzymes in wound healing: the role of enzymatic debridement. AB - Proteolytic enzymes are a family of proteins that serve to degrade necrotic debris derived from cell breakdown. They are produced endogenously often as precursor proteins whose activation is precisely regulated. These activated enzymes serve many functions in normal as well as pathological situations. In particular they are involved in the regulation of cell maturation and multiplication; collagen synthesis and turnover; the development and removal of the perivascular fibrin cuffs found in venous insufficiency and leg ulceration as well as the removal of dead tissues following inflammation. As a limited number of enzymes perform all these functions, it is difficult to predict the effects of applying synthetic proteolytic enzymes to a wound. Many such enzymes are currently commercially available and being promoted as alternatives to surgical wound debridement. It is important for their use to be considered in the context of their interaction with endogenous proteases, their physiological role in tissue, their ability to reach a desired target and the stage of wound healing at the time they are applied. PMID- 7998899 TI - PUVA at the Skin and Cancer Foundation (Melbourne) 1987-1993. PMID- 7998900 TI - Signs, syndromes and diagnoses in dermatology. Neutrophilic eccrine hidradenitis. PMID- 7998901 TI - Fluctuating widespread erythematosquamous eruption and weight loss. PMID- 7998902 TI - Antigenic peptide binding by class I and class II histocompatibility proteins. PMID- 7998903 TI - Superantigens. PMID- 7998904 TI - How the quest to identify minor histocompatibility antigens led to something more important. PMID- 7998905 TI - The recognition of MHC molecules by gamma delta T cells. PMID- 7998906 TI - Rules governing peptide-class II MHC molecule interactions. PMID- 7998907 TI - The interaction between CD4 and MHC class II molecules and its effect on T cell function. AB - During T cell activation, CD4 and CD8 form a 'bridge' between the T cell receptor (TCR) and major histocompatibility complex (MHC) class II and class I molecules, respectively. Due to this intimate association, CD4 and CD8 are now termed co receptors and considered an integral part of this multimolecular complex. In addition, interest in CD4 has been heightened by the discovery that it is, in part, the receptor for HIV. Although CD4 and CD8 appear to perform similar immune functions, they are structurally diverse suggesting that their mode of interaction with the TCR and MHC molecules may differ. This review will focus primarily on a series of studies which have attempted to map the residues which mediate CD4:MHC class II interaction. These data will be evaluated in light of our current understanding of CD8:MHC class I, and CD4:TCR interactions. In addition, a model to explain the structural and functional differences between CD4 and CD8 will be presented. Finally, the potential effect of these multiple interactions on T cell function will be discussed. PMID- 7998908 TI - Association of HLA and multiple sclerosis. AB - Multiple Sclerosis (MS) is a demyelinating disease of the central nervous system. Although the cause of MS is still unknown, it is considered an autoimmune disease based on the composition of inflammatory infiltrates in the brain and on parallels with a T-cell-mediated animal model of demyelinating diseases called experimental allergic encephalomyelitis (EAE). Similar to other autoimmune diseases, the immunogenetic background, in particular the MHC/HLA type, contributes to susceptibility. This review summarizes the current knowledge about the association between HLA background and MS as well as immunological findings in EAE and MS. Finally, an attempt is made to explain how structural interactions between disease-associated HLA type and binding of an autoantigenic peptide could relate to disease. PMID- 7998909 TI - Human major histocompatibility complex genes. PMID- 7998910 TI - Therapeutic intervention in autoimmunity. PMID- 7998911 TI - Peptide transporters and antigen processing. AB - Our knowledge about intracellular pathways involved in the presentation of antigens was considerably broadened with the recent discovery of peptide transporters encoded in the major histocompatibility complex. The transporter associated with antigen processing (TAP) belongs to an evolutionary conserved family of multimembrane-spanning translocators that bind ATP and show specificity for a variety of different substrates. TAP mediates the translocation of peptides, generated by cytosolic degradation of protein antigens, into the lumen of the endoplasmic reticulum where they bind to newly synthesized MHC class I molecules. A novel assay has been employed to elucidate the details of TAP mediated peptide transport. The results indicate that TAP selects peptides of sequence and length according to the requirements of MHC class I molecules in different species. PMID- 7998912 TI - A critical contemplation on the role of heat shock proteins in transfer of antigenic peptides during antigen presentation. AB - Evidence is presented to demonstrate that HSPs mediate transfer of antigenic peptides during antigen presentation by MHC class I-restricted T cells. Transfer of peptides through HSP-chaperones is preferred over direct diffusion of peptides to their destinations because of our belief that few molecular phenomena within cells occur in liquid-phase and there is little evidence for the presence of free peptides in the cell. Further, chaperoning of peptides by HSPs is likely to: (i) shield peptides from their ultimate degradation to single amino acids by cytosolic proteases, (ii) minimize the chances of fortuitous and unproductive coupling with other proteins, (iii) help achieve higher local peptide concentrations than might be possible by passive diffusion, and (iv) obtain a mechanism for the process of transfer to be regulated or modulated. The evidence in support of an involvement of HSPs in transfer of peptides is critically discussed. The theme that HSPs are functional fore-runners of the MHC molecules, first proposed by us (Srivastava and Heike, 1991), is further developed. PMID- 7998913 TI - Laudation presented on the occasion of the bestowal of the Behring Prize to Professor Don C. Wiley. PMID- 7998915 TI - MHC molecules and peptides, structure and function. Dedicated to Don Wiley, recipient of the Emil-von-Behring-Preis 1993. PMID- 7998914 TI - Class I MHC-peptide interaction: structural and functional aspects. AB - The structural requirements for the interaction between antigens and class I molecules was investigated through the use of a quantitative assay to measure peptide binding to different MHC class I alleles. We determined the permissiveness of the main anchors reported by Rammensee and his group for peptide binding and defined an extended motif for peptides binding to the HLA A2.1 allele, including the role of non-anchor positions. It was found that the main anchors were necessary, but not sufficient, for good binding. Certain non anchor positions contributed significantly to overall binding and were referred to a secondary anchors. This finding allowed a better prediction of high affinity binding peptides selected from libraries of different viral and tumor proteins. Furthermore, our data allowed correlation of the structural requirements for binding of peptides with crystallographic data of the MHC molecule. In order to characterize allele-specific motifs for a larger number of alleles, the HLA-A alleles A1, A3, A11, and A24, which represent some of the most common alleles found in different ethnic populations, were chosen. Here, most motifs were found to be highly exclusive; however, HLA-A3 and A11 shared a common motif. The defined motifs were validated further by using naturally processed peptides. Those peptides were also synthesized and tested for binding to the appropriate HLA alleles, giving a binding affinity from 0.3 to 200 nM for sequences of naturally processed peptides. Finally, a set of all possible 9-mer peptides from HPV 16 proteins were synthesized and tested for binding to the five class I alleles. For each allele, high affinity binders were identified, thus allowing for selection of possible peptide candidates for a CTL based vaccine. PMID- 7998916 TI - MHC class I allorecognition: the likes and dislikes of CTL and NK cells. AB - An allogeneic culture was established using cells of two HLA disparate individuals. No pattern of specificity could be discerned when the 6 day culture that contained a mixture of CD4+, CD8+ and CD56+ lymphocytes was tested for cytotoxicity against a panel of target cells. Three approaches were utilized to dissect this alloresponse. A CD8+ population was selected and expanded as a line. This CTL population had predominant specificity for HLA-B35 and showed differential recognition of molecularly defined B35 subtypes. A set of CD8+ T cell clones was selected that recognized B35 transfectant cells. These clones were shown to discriminate among B35 molecular subtypes and to be peptide dependent, presumably recognizing a variety of endogenous peptides expressed in human cells. A second component of the response seemed to be mediated by activated CD56+ lymphocytes. Here strong cytotoxicity was found to be directed against MHC class I mutant cell lines, such as 721.221 and C1R, as well as against some allogeneic target cells. Transfection of Cw7 DNA into the mutant cell lines led to resistance to lysis. A hierarchy in susceptibility was found to correlate with HLA-C type in the unrelated panel: cells expressing HLA-Cw7 were found to be most resistant to lysis by this effector cell population. PMID- 7998918 TI - How are alpha beta T cells positively selected in the thymus? AB - Thymus-derived (T) lymphocytes have the potential to express antigen receptors (TCR) that can recognize both self, as well as foreign antigens as they appear on the cell surface. In the thymus, positive selective allows the maturation of T cells that are able to see foreign antigens in conjunction with molecules encoded by genes of the major histocompatibility complex (MHC), whereas negative selection deletes auto-aggressive T cells. Control of T cell development is the only known function of the thymus. Therefore, it has been argued that recognition events responsible for selection of the T cell repertoire are guided by unique cellular interactions in the thymus. Here, we will show that positive selection can also occur on non-thymic cells. We will also argue that positive selection is not dependent on unique thymic accessory cells (AC) function. In other words, restricted recognition is not taught rather thymocytes learn it by themselves. PMID- 7998917 TI - Tumor rejection antigens and tumor specific cytotoxic T lymphocytes. AB - In several tumor models and in certain types of human malignancies, T cell mediated immune responses can be involved in the host's defences against cancer. Adoptively transferred tumor-specific T cells can mediate complete tumor regression in several animal models and the first effective therapeutic interventions with adoptively transferred (virus-specific) CTL in man have been reported. With the identification of tumor rejection antigens new antigen specific therapeutic approaches come into sight. The development of anti-tumor vaccines based upon known tumor rejection antigens might take off rapidly in the near future, since only the first few tumor rejection antigens of an enormous potential have been reported. This development will go hand in hand with the utilization of cytokines in these vaccines. Cytokines might promote T cell activity or antigen presentation, but can also be used to counteract tumor immune escape mechanisms. Escape from immune surveillance and T cell mediated elimination by tumor cells might account for the failure of the immune system to eradicate or prevent the outgrowth of many types of tumors. The identification of tumor rejection antigens and tumor-specific immune responses, together with a better understanding of the mechanisms by which tumors escape from T cell mediated immunity brings fresh encouragement in the field of tumor immunology. PMID- 7998920 TI - DNA methylation during differentiation of a lower eukaryote, Physarum polycephalum. AB - Starvation-induced differentiation of the slime mould Physarum polycephalum is accompanied by continuous methylation of DNA. No stable changes in the overall level of DNA methylation are evident, but a gene known to be transcribed specifically during differentiation is subject to increased methylation. Inhibitors of DNA methylation preclude differentiation of P. polycephalum, although they are only marginally inhibitory to normal growth. Taken together these results indicate that methylation of DNA is involved in differentiation of this lower eukaryote. PMID- 7998919 TI - Iron regulatory elements (IREs): a family of mRNA non-coding sequences. PMID- 7998921 TI - A low-affinity, low-molecular-mass endothelin-A receptor in neonatal rat heart. AB - Endothelin receptors with endothelin-A (ETa) specificity were present in neonatal rat ventricle. However, in both receptor-binding studies and studies of inositol phosphate accumulation, these receptors had lower affinity for endothelin-1 than ETa receptors on isolated neonatal cardiomyocytes or adult left atria. Receptors in the three myocardial preparations were cross-linked to 125I-endothelin-1 and their molecular masses measured using SDS/PAGE. Receptors on left atria and neonatal cardiomyocytes had the expected molecular mass of 48 kDa, whereas the receptors in neonatal ventricle were smaller (38 kDa). Despite this, neonatal ventricles contained ETa receptor mRNA which was not different in size from that in the isolated cells (4.5 kb). Thus the 38 kDa ETa receptor present in neonatal ventricle appears to be transcribed from full-length ETa receptor mRNA and is possibly formed by processing of the 48 kDa receptor. PMID- 7998922 TI - Non-specific binding of advanced-glycosylation end-products to macrophages outweighs specific receptor-mediated interactions. AB - On binding to murine peritoneal macrophages, maleylated BSA exhibited saturable binding kinetics, with about 24000 sites/cell. Prolonged incubation of BSA with > 20 mM glucose or 2 months incubation with > or = 0.5 M glucose induced the modified protein to readily bind non-specifically to both cell and tube surfaces. Kinetic studies on the binding of advanced glycated end-products (AGEs) and other modified proteins to macrophages and hepatocytes showed no evidence for specific receptor binding, as neither binding saturation nor cross-competition (homologous or heterologous) was detected. Although there was evidence for uptake of BSA which had been incubated with 0.5 M glucose for 2 months, there was no uptake or degradation of AGEs which had been produced at physiological concentrations of glucose. This has implications for the role of macrophages in the recognition of AGEs, and suggests that the non-specific binding may be important in adhesion of AGEs, particularly in poorly controlled diabetics, and might act as a 'damage limitation' mechanism in the potential development of diabetic complications, while low macrophage levels in the blood could seriously potentiate the long-term effects of non-enzymic post-translational protein modifications. PMID- 7998923 TI - Localization of transglutaminase-reactive glutamine residues in bovine osteopontin. AB - Here we report the identification of two transglutaminase-reactive glutamines (Gln-34 and Gln-36) in bovine osteopontin (OPN). Sequence alignment revealed that these glutamines are conserved in all known OPN sequences, indicating a functional importance of this region of the protein. Furthermore, immunological analysis of bovine bone demonstrated that OPN is present in high-molecular-mass complexes in vivo. These findings support the functional aspects of a transglutaminase-catalysed cross-linking of OPN in facilitating cellular attachment and tissue calcification. PMID- 7998924 TI - Purification and characterization of a calcium-independent acidic phospholipase A2 from rat lung. AB - Several phospholipase A2 (PLA2) activities have been identified in rat lung homogenate and shown to be important in metabolism of lung phospholipids. One PLA2 activity is Ca(2+)-independent, active in vitro at pH 4, and inhibited by a substrate analogue, 1-hexadecyl-3-trifluoroethylglycero-sn-2-phosphomethanol (MJ33). Purification of this rat lung PLA2 by approx. 550-fold was carried out by sequential column chromatographies using DE-52, Sephacryl-100, heparin-Sepharose, and phenyl-Sepharose columns. The purified activity had an acidic pH optimum, was Ca(2+)-independent, was inhibited by MJ33 in a dose-dependent manner (50% inhibition at 3 mol%), was unaffected by treatment with p-bromophenacyl bromide or mercaptoethanol, and had a unique N-terminal amino acid sequence. The apparent molecular mass was 15 kDa on gel electrophoresis and activity was recovered in part by renaturation of protein from the gel. The properties of this enzyme suggest a new class of PLA2. PMID- 7998925 TI - Expression of vesicle-associated membrane protein 2 (VAMP-2)/synaptobrevin II and cellubrevin in rat skeletal muscle and in a muscle cell line. AB - Molecular studies have identified a family of synaptic vesicle-associated membrane proteins (VAMPs, also known as synaptobrevins) which have been implicated in synaptic vesicle docking and/or fusion with plasma membrane proteins. Here we demonstrate the expression of two members of this family, VAMP 2/synaptobrevin II and cellubrevin, in skeletal muscle, a tissue with both constitutive and regulated membrane traffic. The 18 kDa VAMP-2 polypeptide was detected in purified membrane fractions from adult skeletal muscle and from L6 myotubes in culture, demonstrating that the presence of this protein in the isolated muscle membrane fractions is not the result of contamination by ancillary tissues such as peripheral nerve. Furthermore, skeletal muscle and the muscle cell line also expressed cellubrevin, a VAMP-2 homologue of 17 kDa; which is much less abundant in brain cells. Both VAMP-2 and cellubrevin were preferentially isolated in membrane fractions rich in plasma membranes, and were less concentrated in light microsomes and other internal membrane fractions of mature muscle or muscle cells in culture. Interestingly, both VAMP-2 and cellubrevin were much more abundant in the differentiated L6 myotubes than in their precursor myoblasts, suggesting that they are required for functions of differentiated muscle cells. The identity of both polypeptides was further confirmed by their susceptibility to proteolysis by Clostridium tetanus toxin. Expression of these products was further established by the presence of mRNA transcripts of VAMP-2 and cellubrevin, but not of VAMP-1, in both skeletal muscle and L6 myotubes. In contrast, other synaptic vesicle and docking/fusion components were undetectable, such as VAMP-1, SNAP25 and syntaxin 1A/1B, as were synaptophysin and synapsin Ia/Ib, proteins which are believed to be involved in sensing the signal for neuronal exocytosis. It is concluded that VAMP-2 and cellubrevin are expressed in skeletal muscle cells and may each participate in specific processes of intracellular membrane traffic. PMID- 7998926 TI - Differential effects of 9-cis and all-trans retinoic acid on the induction of retinoic acid receptor-beta and cellular retinoic acid-binding protein II in human neuroblastoma cells. AB - The objective of this study was to compare the properties of 9-cis and all-trans retinoic acid with respect to the induction of expression of retinoic acid receptor beta (RAR-beta) and cellular retinoic acid-binding protein (CRABP) II in human neuroblastoma SH SY 5Y cells. RAR-beta and CRABP II mRNA was induced by both all-trans and 9-cis retinoic acid in SH SY 5Y cells. Induction was rapid, detectable within 2-4 h, and inhibited by actinomycin D. Time-courses of induction for RAR-beta and CRABP II differed: RAR-beta mRNA levels reached a maximum 4-6 h after adding all-trans or 9-cis retinoic acid, whereas CRABP II mRNA levels increased over at least 18 h. These differences were attributed to the longer half-life of CRABP II mRNA (20 h) compared with RAR-beta mRNA (3.9 h). The dose-response characteristics of all-trans and 9-cis retinoic acid were different: all-trans was effective at nanomolar concentrations, whereas 10-fold higher levels of 9-cis retinoic acid were required to achieve comparable induction of RAR-beta and CRABP II. Conversely, at high concentrations, 9-cis retinoic acid gave a greater induction of RAR-beta and CRABP II than all-trans. The induction of RAR-beta and CRABP II by all-trans retinoic acid was maintained in the subsequent absence of all-trans retinoic acid, whereas induction by 9-cis retinoic acid was dependent on its continued presence in the culture medium. These results suggest that, at high concentrations, 9-cis retinoic acid may produce its transcriptional effects via retinoid X receptor (RXR) homodimers. This has implications for the cellular functions of 9-cis retinoic acid and its use as a biological response modifier. PMID- 7998927 TI - Oxidation of monohydric phenol substrates by tyrosinase: effect of dithiothreitol on kinetics. AB - The effect of thiol compounds on the monophenolase activity of tyrosinase was investigated using 4-hydroxyanisole as the substrate and dithiothreitol (DTT) as the model thiol compound. We have demonstrated three actions of DTT on tyrosinase catalysed reactions: (1) direct reduction of the copper at the active site of the enzyme; (2) generation of secondary, oxidizable species by adduct formation with the o-quinone reaction product, 4-MOB, which leads to an increase in the total oxygen utilization by the reaction system; and (3) reversible inhibition of the enzyme. We confirm our previous observation that, at approx. 10 mol of DTT/mol of enzyme, the lag phase associated with monohydric phenol oxidation by tyrosinase is abolished. We suggest that this is due to reduction of the copper at the active site of the enzyme by DTT, since (a) reduction of active-site copper in situ by DTT was demonstrated by [Cu(I)]2-carbon monoxide complex formation and (b) abolition of the lag at low DTT concentration occurs without effect on the maximum rate of reaction or on the total amount of oxygen utilized. At concentrations of DTT above that required to abolish the lag, we found that the initial velocity of the reaction increased with increasing DTT, with a concomitant increase in the total oxygen utilization. This is due to the formation of DTT-4-methoxy-o-benzoquinone (4-MOB) adducts which provide additional dihydric phenol substrate either directly or by reducing nascent 4 MOB. We present n.m.r. evidence for the formation of mono- and di-aromatic DTT adducts with 4-MOB, consistent with a suggested reoxidation scheme in the presence of tyrosinase. Inhibition of the enzyme at concentrations of DTT above 300 pmol/unit of enzyme was released on exhaustion of DTT by adduct formation with 4-MOB as it was generated. PMID- 7998928 TI - Decrease in S-adenosylmethionine synthesis by 6-mercaptopurine and methylmercaptopurine ribonucleoside in Molt F4 human malignant lymphoblasts. AB - 6-Mercaptopurine (6-MP) and methylmercaptopurine ribonucleoside (Me-MPR) are purine anti-metabolites which are both metabolized to methylthio-IMP (Me-tIMP), a strong inhibitor of purine synthesis de novo. Me-MPR is converted directly into Me-tIMP by adenosine kinase. 6-MP is converted into tIMP, and thereafter it is methylated to Me-tIMP by thiopurine methyltransferase, an S-adenosylmethionine (S Ado-Met)-dependent conversion. S-Ado-Met is formed from methionine and ATP by methionine adenosyltransferase, and is a universal methyl donor, involved in methylation of several macromolecules, e.g. DNA and RNA. Therefore, depletion of S-Ado-Met could result in an altered methylation state of these macromolecules, thereby affecting their functionality, leading to dysregulation of cellular processes and cytotoxicity. In this study the effects of 6-MP and Me-MPR on S-Ado Met, S-adenosylhomocysteine (S-Ado-Hcy), homocysteine and methionine concentrations are determined. Both drugs cause a decrease in intracellular S-Ado Met concentrations and an increase in S-Ado-Hcy and methionine concentrations in Molt F4 human malignant lymphoblasts. The effects of both 6-MP and Me-MPR can be ascribed to a decreased conversion of methionine into S-Ado-Met, due to the ATP depletion induced by the inhibition of purine synthesis de novo by Me-tIMP. Both 6-MP and Me-MPR thus affect the methylation state of the cells, and this may result in dysregulation of cellular processes and may be an additional mechanism of cytotoxicity for 6-MP and Me-MPR. PMID- 7998929 TI - Modulation of complement regulatory function and measles virus receptor function by the serine-threonine-rich domains of membrane cofactor protein (CD46). AB - Three major membrane cofactor protein (MCP) phenotypes with different serine threonine (ST)-rich regions, namely STc (L-phenotype), STBC (H or U phenotype) and STABC, and the MCP without the ST domain (delta ST) were expressed in Chinese hamster ovary (CHO) cells by transfecting the respective cDNAs. The expressed molecules migrated with a larger molecular mass on SDS/PAGE than those expected from their amino acid sequences. O-Glycanase digestion showed that this was due to O-linked sugar chains. The apparent sugar contents in each ST segment were compatible with their serine and threonine contents in the ST regions. The functional properties of these phenotypes as inhibitors of human complement (C) and receptors of measles virus (MV) were compared. The classical pathway dependent CHO cell lysis by human C was more effectively suppressed by the expressed delta ST and STC than by the STABC and STBC phenotypes, although the difference was not so prominent. In contrast, alternative C pathway-dependent CHO cell lysis was most effectively suppressed by the STABC phenotype and was only slightly blocked by the ST-deleted mutant. MV infection occurred with all of the phenotypes, but the infectious dose required to cause the same level of syncytium formation was 100-times higher in large ST (STABC and STBC) than in small ST (STC and delta ST) phenotypes. Thus, the ST domain serves as a functional modulator in MCP: MCP with a large ST domain having high O-linked sugar contents is favourable to the effective suppression of both the alternative C pathway-mediated cytolysis and MV infection, whereas MCP with a small ST domain is favourable to the suppression of the classical C pathway. PMID- 7998930 TI - Insulin receptor substrate 1 is phosphorylated by the serine kinase activity of phosphatidylinositol 3-kinase. AB - Insulin receptor substrate (IRS) 1, which is tyrosine phosphorylated in response to insulin, presents multiple serine/threonine phosphorylation sites. To search for a serine kinase activity towards IRS 1, immunoprecipitates from basal or stimulated 3T3-L1 adipocytes were used in an in vitro kinase assay. When IRS 1 was isolated from insulin-treated cells, serine phosphorylation of IRS 1 occurred, which we attribute to the kinase activity of the phosphatidylinositol 3 kinase (PI3-kinase). Importantly, in an in vitro reconstitution assay, an excess of the PI3-kinase subunit prevents this phosphorylation. Together, our results suggest that following insulin stimulation, PI3-kinase associates with IRS 1, allowing for its serine phosphorylation. This phosphorylation event could play a role in the modulation of insulin signalling. PMID- 7998931 TI - Effects of insulin treatment of diabetic rats on hepatic partitioning of fatty acids between oxidation and esterification, phospholipid and acylglycerol synthesis, and on the fractional rate of secretion of triacylglycerol in vivo. AB - 1. The hypothesis that insulin treatment of streptozotocin-diabetic rats does not alter acutely the ability of acylcarnitine synthesis to compete successfully for cytosolic long-chain acyl-CoA [Grantham and Zammit (1988) Biochem. J. 249, 409 414], was tested in vivo by using the technique of selective labelling of hepatic fatty acids in awake unrestrained rats. In the same animals, the partitioning of hepatic fatty acids between acylglycerol and phospholipid synthesis, and of newly labelled triacylglycerol between secretion into the plasma and retention in the liver, was also studied. 2. In untreated diabetic animals, the ratio of fatty acid oxidation to esterification was double that found in normal fed animals, whereas there were no differences in the values of the above-mentioned parameters of glycerolipid metabolism. Thus the insulin status of the rats only has chronic effects on specific aspects of fatty acid metabolism in the liver. 3. Treatment of diabetic rats with insulin resulted in no change in the oxidation/esterification ratio for the first 5 h after the start of insulin administration. Thereafter, there were reciprocal changes in the 14CO2 expired (an index of oxidation) and 14C label recovered in hepatic and plasma glycerolipids. However, the pattern of partitioning observed in normal fed rats was still not re-established after 8 h of insulin treatment. 4. There was a small and transient decrease in the fractional rate of triacylglycerol secretion by the liver at the start of insulin treatment and an increase in the proportion of labelled fatty acid that was utilized for phospholipid synthesis such that phospholipid labelling as a proportion of that of total glycerolipids was doubled after 8 h of insulin treatment. 5. The data are discussed in relation to the roles of insulin in mediating acute changes in hepatic fatty acid metabolism and very-low-density-lipoprotein triacylglycerol secretion by the liver. PMID- 7998932 TI - Forced expression of antizyme abolishes ornithine decarboxylase activity, suppresses cellular levels of polyamines and inhibits cell growth. AB - Ornithine decarboxylase (ODC) is a key enzyme in polyamine biosynthesis. It is a short-lived protein and negatively regulated by its products, polyamines. Its degradation is accelerated by the binding of antizyme, an ODC-inhibitory protein induced by polyamines. To evaluate the physiological importance of antizyme we examined the effect of forced expression of antizyme on cellular ODC and polyamine levels and cell growth. Antizyme almost completely abolished the induction of ODC by growth stimuli. This may have been caused by antizyme-induced rapid degradation of newly synthesized ODC, since the half-life of ODC complexes with antizyme was less than 5 min. Forced expression of antizyme caused reductions of cellular putrescine and spermidine levels, and inhibited cell growth, which was partially restored by the addition of putrescine. These observations suggested a critically important role of antizyme in polyamine metabolism. PMID- 7998933 TI - Purification and further characterization of peroxisomal trihydroxycoprostanoyl CoA oxidase from rat liver. AB - The acyl-CoA oxidase, catalysing the peroxisomal desaturation of the CoA-ester of trihydroxycoprostanic acid, a bile acid intermediate, has been purified to homogeneity from rat liver. Its native molecular mass, as determined by gel filtration and native gel electrophoresis, was 120 and 175 kDa respectively, suggesting a homodimeric protein consisting of 68.6 kDa subunits. If isolated in the presence of FAD, the enzyme showed a typical flavoprotein spectrum and contained most likely 2 mol of FAD per mol of enzyme. The cofactor, however, was loosely bound. The enzyme acted exclusively on 2-methyl-branched compounds, including pristanoyl-CoA and 2-methylhexanoyl-CoA if albumin was present. Important parameters to obtain a pure and active enzyme were the following: (1) using chromatographic separations like hydrophobic interaction and metal affinity, which allow the presence of high salt concentrations, conditions which stabilize the oxidase; (2) avoiding dialysis and (NH4)2SO4 precipitation; (3) including, when appropriate, FAD, dithiothreitol and a diol-compound in the solvents; and (4) carefully monitoring the removal of other acyl-CoA oxidases which possess the same native molecular mass and subunit size. PMID- 7998935 TI - Evidence for the existence of lipid-diffusion barriers in the equatorial segment of human spermatozoa. AB - Liposomes consisting of negatively charged phospholipids interact almost exclusively with the equatorial segment (ES) of human spermatozoa provided the cells have undergone the acrosome reaction (AR) [Arts, Kuiken, Jager and Hoekstra (1993) Eur. J. Biochem. 217, 1001-1009]. Using fluorescently tagged liposomes, this interaction can be observed by fluorescence microscopy, showing either a diffuse fluorescence in the ES region (pattern ESd, presumably reflecting membrane-incorporated lipids as a result of fusion) or a punctate fluorescence (pattern ESp, representing adhering liposomes). These distribution patterns remain unchanged during prolonged incubation, up to 40 min. Not only do these observations suggest the existence of fairly specific liposomal binding sites, associated with the ES region, but also that a barrier to lipid lateral diffusion seems to exist in the ES membrane. Using liposomes that contain fluorescent lipid analogues in either both leaflets or in the inner leaflet only, we demonstrate that this putative barrier entails both membrane leaflets. Treatment with EDTA caused fluorescence to spread from the ES towards other membrane domains. Since only spermatozoa displaying pattern ESd were affected by the chelator, the randomization was not caused by EDTA-induced fusion activity. Therefore, this observation provides further evidence that in spermatozoa displaying pattern ESd the fluorescent lipid analogues were incorporated in the ES membrane as a result of fusion. Furthermore, these experiments support the view of the existence of a transmembranous block to lipid lateral diffusion in the ES, the stability of which may be governed by bivalent cations. PMID- 7998934 TI - Adenosine A1 receptors mediate chronic ethanol-induced increases in receptor stimulated cyclic AMP in cultured hepatocytes. AB - Cellular responses to adenosine depend on the distribution of the two adenosine receptor subclasses. In primary cultures of rat hepatocytes, adenosine receptors were coupled to adenylate cyclase via A1 and A2 receptors which inhibit and stimulate cyclic AMP production respectively. R-(-)-N6-(2-phenylisopropyl) adenosine (R-PIA), the adenosine A1 receptor-selective agonist, inhibited glucagon-stimulated cyclic AMP production with an IC50 of 19 nM. This inhibition was blocked by the A1-specific antagonist 8-cyclopentyl-1,3-dimethylxanthine (CPDX). 5'-N- Ethylcarboxamidoadenosine (NECA), an agonist which stimulates A2 receptors, increased cyclic AMP production with an EC50 of 0.6 microM. Treatment of primary cultures of rat hepatocytes with 100 mM ethanol for 48 h decreases the quantity and function of the inhibitory guanine-nucleotide regulatory protein (G(i)), resulting in a sensitization of receptor-stimulated cyclic AMP production [Nagy and deSilva (1992) Biochem. J. 286, 681-686]. When cells were cultured with 2 units/ml adenosine deaminase, to degrade extracellular adenosine, ethanol induced increases in cyclic AMP production were completely prevented. Moreover, the specific A1-receptor antagonist, CPDX, also blocked the chronic effects of ethanol on receptor-stimulated cyclic AMP production. Treatment with adenosine deaminase or CPDX also prevented the decrease in quantity of the alpha subunit protein of G(i) observed in hepatocytes after chronic treatment with ethanol. Taken together, these results suggest that activation of adenosine A1 receptors on primary cultures of hepatocytes is involved in the development of chronic ethanol-induced sensitization of receptor-stimulated cyclic AMP production. PMID- 7998936 TI - DNA cleavage induced by glycation of Cu,Zn-superoxide dismutase. AB - Human Cu,Zn-superoxide dismutase (Cu,Zn-SOD) undergoes site-specific and random fragmentation by non-enzymic glycosylation (glycation). Released Cu2+ from the glycated Cu,Zn-SOD probably facilitates a Fenton reaction to convert H2O2 into hydroxy radical, which then participates in the non-specific fragmentation [Ookawara et al. (1992) J. Biol. Chem. 267, 18505-18510]. In the present study, we investigated the effects of glycated Cu,Zn-SOD on cloned DNA fragments and nuclear DNA and analysed the formation of 8-hydroxydeoxyguanosine (8-OH-dG). Incubation of cloned DNA fragments with Cu,Zn-SOD and reducing sugars resulted in cleavage of the DNA. The extent of the cleavage corresponded to the reducing capacity of the sugar. Metal-chelating reagents, EDTA and bathocuproine, and an H2O2 scavenger, catalase, inhibited the DNA cleavage. Hydroxy radical scavengers and aminoguanidine, an inhibitor of glycation, also inhibited the reaction. Moreover, the glycation of Cu,Zn-SOD caused the substantial formation of 8-OH-dG in DNA. When isolated nuclei were incubated with CuCl2 plus H2O2, nuclear DNA cleavage was observed. Incubation of isolated nuclei with Cu,Zn-SOD that had been pre-incubated with glucose also resulted in nuclear DNA cleavage. These results suggest that hydroxy radical is produced through a Fenton reaction by Cu2+ and H2O2 released from the glycated Cu,Zn-SOD, and participates in nuclear DNA cleavage. This mechanism may partly explain the deterioration of organs under diabetic conditions. PMID- 7998938 TI - The novel behaviour of interactions between Ni2+ ion and human or bovine serum albumin. AB - We discovered a series of novel behaviours of interactions between Ni2+ ion and human or bovine serum albumin. Our results indicated that there exist two closely neighbouring identical prior binding sites in the binding of human or bovine serum albumin with Ni2+ ions, not only one. It is very likely that, after the binding of the first Ni2+ ion, an induced slow conformational transition happens, which leads to the binding of the second Ni2+ ion and shows itself as a hysteretic effect for a process of non-enzymic protein binding with metal ions. As the concentrations of the 1:1 (molar ratio of Ni2+ ion to protein) system increase, an increasing hypochromic effect is observed. Such a hypochromic effect has not been reported previously; however, it is in accord with the mechanism of dipole-dipole interactions between the electric dipole transition moments of chromophores. PMID- 7998937 TI - Ca2+/H+ exchange in acidic vacuoles of Trypanosoma brucei. AB - The use of digitonin to permeabilize the plasma membrane of Trypanosoma brucei procyclic and bloodstream trypomastigotes allowed the identification of a non mitochondrial nigericin-sensitive Ca2+ compartment. The proton ionophore carbonyl cyanide p-trifluoromethoxyphenylhydrazone (FCCP) was able to cause Ca2+ release from this compartment, which was also sensitive to sodium orthovanadate. Preincubation of the cells with the vacuolar H(+)-ATPase inhibitor bafilomycin A1 greatly reduced the nigericin-sensitive Ca2+ compartment. Bafilomycin A1 inhibited the initial rate of ATP-dependent non-mitochondrial Ca2+ uptake and stimulated the initial rate of nigericin-induced Ca2+ release by permeabilized procyclic trypomastigotes. ATP-dependent and bafilomycin A1- and 7-chloro-4 nitrobenz-2-oxa-1,3-diazole (NBD-Cl)-sensitive Acridine Orange uptake was demonstrated in permeabilized cells. Under these conditions Acridine Orange was concentrated in abundant cytoplasmic round vacuoles by a process inhibited by bafilomycin A1, NBD-Cl, nigericin, and Ca2+. Vanadate or EGTA significantly increased Acridine Orange uptake, while Ca2+ released Acridine Orange from these preparations, thus suggesting that the dye and Ca2+ were being accumulated in the same acidic vacuole. Acridine Orange uptake was reversed by nigericin, bafilomycin A1 and NH4Cl. The results are consistent with the presence of a Ca2+/H(+)-ATPase system pumping Ca2+ into an acidic vacuole, that we tentatively named the acidocalcisome. PMID- 7998939 TI - Function of streptokinase fragments in plasminogen activation. AB - Several peptide fragments of streptokinase (SK) were prepared by incubating SK with immobilized human plasmin (hPlm) and purified by h.p.l.c. with a reverse phase phenyl column. The N-terminal sequences, amino acid compositions and molecular masses of these peptide fragments were determined. The SK peptide fragment of 36 kDa consisting of Ser60-Lys387 (SK-p), was the only peptide fragment that could be tightly bound to immobilized hPlm. Another three large SK peptide fragments, SK-m, SK-n and SK-o, with molecular masses of 7 kDa, 18 kDa and 30 kDa, and consisting of Ile1-Lys59, Glu148-Lys333, Ser60-Lys333 respectively, were also obtained from the supernatant of the reaction mixture. The purified SK-p had high affinity with hPlm and could activate human plasminogen (hPlg) with a kPlg one-sixth that of the native SK. SK-o had low affinity with hPlm and could also activate hPlg, although the catalytic constant was less than 1% of the native SK. SK-n, as well as SK-m, which is the N-terminal 59 amino acid peptide of the native SK, had no activator activity. However, SK-m could enhance the activator activity of both SK-o and SK-p and increase their second-order rate constants by two- and six-fold respectively. It was concluded from these studies that (1) SK-o, the Ser60-Lys333 peptide of SK, was essential for minimal SK activator activity, (2) the C-terminal peptide of SK-p, Ala334 Lys387, was essential for high affinity with hPlm, and (3) the N-terminal 59 amino-acid peptide was important in maintaining the proper conformation of SK to have its full activator activity. PMID- 7998941 TI - Lithium stimulates accumulation of second-messenger inositol 1,4,5-trisphosphate and other inositol phosphates in mouse pancreatic minilobules without inositol supplementation. AB - Previous studies showed that lithium, beginning at therapeutic plasma concentrations in the treatment of manic depression, increased the accumulation of second-messenger inositol 1,4,5-trisphosphate [Ins(1,4,5)P3] in cerebral cortex slices of guinea pig and rhesus monkey [Lee, Dixon, Reichman, Moummi, Los and Hokin (1992) Biochem. J. 282, 377-385; Dixon, Lee, Los and Hokin (1992) J. Neurochem. 59, 2332-2335; Dixon, Los and Hokin (1994) Proc. Natl. Acad. Sci. U.S.A. 91, 8358-8362]. These studies have now been extended to a peripheral tissue, mouse pancreatic minilobules. In the presence of carbachol, concentrations of lithium from 1 to 20 mM sharply and progressively increased the accumulation of Ins(1,4,5)P3 and inositol 1,3,4,5-tetrakisphosphate, followed by a decrease. Assay of these inositol polyphosphates by either the prelabelling technique or mass assay gave similar results. Atropine quenching of cholinergically stimulated pancreatic minilobules led to a rapid disappearance of Ins(1,4,5)P3. This disappearance was impeded by lithium. This suggested that the lithium-induced elevation in Ins(1,4,5)P3 was due to inhibition of the 5 phosphatase and, on the basis of the markedly elevated concentrations of inositol 1,3,4-trisphosphate [Ins(1,3,4)P3] and inositol 1,4-bisphosphate in the presence of lithium, probably by feedback inhibition by these latter two compounds. An additional mechanism, i.e. a stimulatory effect of lithium on phospholipase C, cannot, however, be ruled out. The other reaction product of phospholipase C, inositol cyclic 1:2,4,5-trisphosphate, also increased in the presence of lithium. This may also be due to inhibition of the 5-phosphatase, which is the exclusive mechanism for removal of this compound. The effects of lithium on the accumulation of other inositol phosphates paralleled that of Ins(1,4,5)P3, with the exception of inositol 3,4-bisphosphate, which decreased. This was presumably due to the inhibition of Ins(1,3,4)P3 1-phosphatase by lithium. Unlike mouse cerebral cortex slices [Lee, Dixon, Reichman, Moummi, Los and Hokin (1992) Biochem. J. 282, 377-385], inositol supplementation was not required to demonstrate lithium-stimulated Ins(1,4,5)P3 accumulation in mouse pancreatic minilobules. This indicates that inositol depletion sufficient to impair lithium stimulated Ins(1,4,5)P3 accumulation does not occur in mouse pancreatic minilobules, even though an elevation of cytidine diphosphodiacylglycerol occurred, indicating some inositol depletion due to lithium. Elevation of Ins(1,4,5)P3 by lithium may be a general phenomenon in the central nervous system and peripheral tissues under non-rate-limiting concentrations of inositol. PMID- 7998940 TI - Tyrosine phosphorylation and activation of NADPH oxidase in human neutrophils: a possible role for MAP kinases and for a 75 kDa protein. AB - Challenge of neutrophils with concanavalin A (ConA), formyl-methionyl-leucyl phenylalanine (FMLP), and phorbol 12-myristate 13-acetate (PMA) induced the tyrosine phosphorylation of several proteins. Among these proteins we have identified two mitogen-activated protein kinase (MAPK) isoforms of 43 kDa (p43 MAPK) and 45 kDa (p45 MAPK) molecular mass. Moreover here we show that: (1) FMLP induced the tyrosine phosphorylation of the p43 MAPK, and ConA that of p45 MAPK, while PMA induced the tyrosine phosphorylation of both p43 and p45 MAPK; all these agonists induced the tyrosine phosphorylation of a 75 kDa protein (p75). (2) With FMLP or ConA as agonists, tyrosine phosphorylations of MAPK and p75 can be involved in the process of NADPH oxidase activation. On the contrary, PMA can activate the respiratory burst independently of these phosphorylations. (3) In Ca(2+)-depleted neutrophils, where phospholipid hydrolysis did not take place, ConA or FMLP did not activate the respiratory burst, but while ConA induced the tyrosine phosphorylation of p45 MAPK and p75, FMLP was not able to phosphorylate p43 MAPK and p75. (4) As previously observed in our laboratory, a double stimulation of Ca(2+)-depleted neutrophils with ConA plus FMLP induced a respiratory burst in the absence of activation of second messengers derived from phospholipase C, D and A2 activity. This respiratory burst was accompanied by tyrosine phosphorylation of both p43 and p45 MAPKs. These results indicate that when FMLP is the agonist, both the tyrosine phosphorylation of p43 MAPK and p75, and the activation of NADPH oxidase, are coupled to Ca(2+)-dependent mechanisms. On the contrary, ConA can induce the tyrosine phosphorylation of p45 MAPK and p75 independently of calcium, but an unknown Ca(2+)-dependent mechanism is necessary for the activation of NADPH oxidase by this agonist. This mechanism could be substituted by the induction of tyrosine phosphorylation of both p43 MAPK and p45 MAPK when Ca(2+)-depleted neutrophils are stimulated with ConA plus FMLP. PMID- 7998942 TI - Development of thyroxine type II deiodinase activity in brains of Zucker rats. AB - The present study was undertaken to determine whether the capacity for 3,5,3',5' tetraiodothyronine (T4) conversion into 3,5,3'-tri-iodothyronine (T3), as measured by the activity of thyroxine type II 5'-monodeiodinase (T4-5'D), was altered in the brains of young Zucker fa/fa rats during the period of intense maturation of the central nervous system (i.e. from 10 to 20 days of life). From 7 to 14 days of age, no difference in brain T4-5'D activity could be detected between lean and pre-obese rats; serum free T4 was not affected by the fa gene. During the suckling to weaning transition, T4-5'D reached a plateau in brains of lean rats, while it increased by 50% in brains of pre-obese rats; concurrently, serum free T4 increased in Fa/fa rats, whereas it did not change in fa/fa rats. The increased capacity for conversion of T4 into T3 observed in brains of pre obese compared with lean rats could not be ascribed to a variation in the amount of T4-5'D, since Vmax. did not differ between the two genotypes; however, it could be totally accounted for by an increased affinity of the enzyme for T4. This change may represent an adaptive response to low serum free T4 in order to maintain the cerebral T3 concentration in pre-obese rats. These results show that the alteration in T4 metabolism in brains of fa/fa rats is not an early event and thus cannot interfere with maturation of the central nervous system. However, the decreased serum free T4 which was observed in pre-obese rats after suckling might play a secondary role in development of this genetic obesity. PMID- 7998943 TI - Cell surface-mediated activation of progelatinase A: demonstration of the involvement of the C-terminal domain of progelatinase A in cell surface binding and activation of progelatinase A by primary fibroblasts. AB - We report that the isolated C-terminal domain of progelatinase A is inhibitory to the activation of this proenzyme by primary skin fibroblast plasma membranes but is unable to inhibit organomercurial-induced self-cleavage and activation. Ligand binding studies demonstrate that fibroblasts stimulated with concanavalin A to activate progelatinase A have a significantly enhanced level of cell surface associated progelatinase A. Tissue inhibitor of metalloproteinases-2 (TIMP-2), an effective inhibitor of membrane-mediated progelatinase A activation, is able to abolish the enhanced level of cell surface-associated progelatinase A that occurs following stimulation. TIMP-1, a poor inhibitor of membrane activation, is unable to inhibit the cell surface binding of progelatinase A. The enhancement in the binding of 125I-progelatinase A to fibroblasts following concanavalin A stimulation can be blocked by the inclusion of excess C-terminal gelatinase A but not by a truncated form of gelatinase A lacking the C-terminal domain. Scatchard analysis of the binding of 125I-progelatinase A to concanavalin A-stimulated fibroblasts has identified 950,000 gelatinase binding sites per cell with a Kd of 1.3 x 10(-8) M. Analysis of non-stimulated fibroblasts has identified 500,000 sites per cell with a Kd of 2.6 x 10(-8) M. We propose that membrane-mediated activation of progelatinase A involves binding of the proenzyme through its C terminal domain to the cell surface and that TIMP-2 can inhibit activation by interaction with progelatinase A through the C-terminal domain, thus preventing binding of the proenzyme. PMID- 7998944 TI - Structural requirements of apo-a for the lipoprotein-a assembly. AB - Lipoprotein-a [Lp(a)], one of the most atherogenic lipoproteins, is composed of a low-density lipoprotein (LDL) core in addition to an apo-a of variable size which is linked to apoB by a disulphide bridge. Lp(a) synthesized in vitro by incubation of recombinant apo-a (r-apo-a) with LDL is physico-chemically indistinguishable from native Lp(a). The synthesis of Lp(a) in vitro proceeds in two steps. In the first step, one of the unique kringle-IVs (K-IVs) in apo-a binds to a Lys residue of apoB; in the second step, Cys-4057 of K-IV type-9 (T-9) forms a disulphide bridge with Cys-3734 of LDL. Here we have produced r-apo-a with different combinations of unique K-IVs and shown that K-IV T-6 is required for the first step of Lp(a) assembly. For the second step not only is K-IV T-9 essential, but also the distance between T-6 and T-9 requires a length of two K IVs. These findings give additional insight into the mode of Lp(a) assembly and are of relevance in the search for apo-a mutants influencing Lp(a) levels and for the development of Lp(a)-lowering medications. PMID- 7998945 TI - DNA-binding characterization of a novel anti-tumour benzo[a]phenazine derivative NC-182: spectroscopic and viscometric studies. AB - NC-182 is a novel anti-tumour compound having a benzo[a]phenazine ring. Fluorescence, absorption and c.d. spectroscopy, as well as viscometric titrations, were systematically performed to investigate the interaction mode of this drug with DNA and its effect on DNA conformation, based on comparative measurements with distamycin (DNA minor-groove binder) and daunomycin (DNA-base intercalator). NC-182 was found to be a potent intercalator of DNA, especially the B-form DNA, although no specificity was observed against the base-pair. The binding of NC-182 to B-DNA behaves biphasically, depending on the molar ratio (r) of drug to DNA: NC-182 acts to render the B-form structure rigid at relatively low r value and to promote the transformation of B- to non-B forms at high r values. It was also shown that NC-182 promotes the unwinding of Z-form DNA to B form. Viscometric, u.v. 'melting' and c.d. experiments further showed that (1) the DNA duplex structure is thermally stabilized by intercalation with NC-182 and (2) the intercalation of NC-182 into a poly(dA).2poly(dT) DNA structure thermally stabilizes the triplex structure, resulting in a melting point close to that of the duplex structure; the melting curves of triplex and duplex structures coincide at r > 0.06. These observations make a significant contribution to our understanding of the biological properties of this novel benzo[a]phenazine derivative, a new anti-tumour tumour agent against multidrug-resistant and sensitive tumours. PMID- 7998946 TI - Kinetic mechanism and characterization of human beta-galactosidase precursor secreted by permanently transfected Chinese hamster ovary cells. AB - Chinese hamster ovary cell clones permanently transfected with the cDNA for human lysosomal beta-galactosidase secrete the enzyme precursor into the cell medium, from which it is purified to apparent homogeneity in a single step by affinity chromatography. The purified precursor is fully active, displays the same pH optimum and Km values as the mature placental enzyme, and has an intact C terminus. The intact enzyme when chromatographed on a Sephacryl S-200 molecular sieve column elutes as a 105,500 Da monomer, whereas on SDS/PAGE gels the polypeptide migrates as an 88 kDa polypeptide. A time course of digestion with glycopeptide-N-glycanase shows the gradual conversion of the precursor from an 88 to a 72 kDa protein, suggesting the presence of five N-linked oligosaccharides in the protein. The precursor is readily taken up in a mannose-6-phosphate-dependent manner into beta-galactosidase-deficient, GM1-gangliosidosis fibroblasts, and the enzyme activity is returned to normal levels. We show that the stereochemical course of enzymic hydrolysis involves the retention of the beta-configuration at the anomeric centre, suggesting a double-displacement mechanism. Furthermore, the enzyme is rapidly and irreversibly inactivated in the presence of the mechanism based inactivator 2,4-dinitrophenyl-2-deoxy-2-fluoro-beta-D-galactopyranoside, which implicates a covalent intermediate. The enzyme is also inactivated by 1 ethyl-3(3-dimethylamino-propyl)carbodi-imide and by phenylglyoxal, which implicates carboxylate and arginine residues respectively in the active site. We conclude that the beta-galactosidase precursor is functionally identical to the mature lysosomal form of the enzyme and serves as an excellent enzyme source for investigation of structure-function relationships in the protein. PMID- 7998947 TI - Site-directed mutagenesis of the putative active site of human 17 beta hydroxysteroid dehydrogenase type 1. AB - Several amino acid residues (Cys54, Tyr155, His210, His213 and His221) at a putative catalytic site of human 17 beta-hydroxysteroid dehydrogenase type 1 were mutated to Ala. Replacement of His221 by Ala remarkably reduced the catalytic activity, which resulted from a change of both the Km and the Vmax. values of the enzyme. Compared with the wild-type enzyme, the catalytic efficiency of the His221-->Ala mutant was reduced 20-fold for the oxidative reaction and 11-fold for the reductive reaction. With similar mutations at His210 or His213, no notable effects on the catalytic properties of the enzyme were detected. However, a simultaneous mutation of these amino acid residues decreased the Vmax. values of both oxidation and reduction by about 50% from those measured for the wild type enzyme. Although Cys54 has been localized in the cofactor-binding region of the enzyme, a Cys54-->Ala mutation did not lead to changes in the enzymic activity. The most dramatic effects on the catalytic properties of the enzyme were achieved by mutating Tyr155, which resulted in an almost completely inactivation of the enzyme. The decreased enzymic activities of the Tyr155-->Ala, His210-->Ala + His213-->Ala and His221-->Ala mutations were also reflected in a reduced immunoreactivity of the enzymes. The results thus suggest that the lower catalytic efficiency of the mutant enzymes is due to an exchange of catalytically important amino acid residues and/or remarkable alterations in the three dimensional structure of the enzyme. The recently detected polymorphisms (Ala237< ->Val and Ser312<-->Gly) were not found to affect either the catalytic or the immunological properties of the type 1 enzyme. PMID- 7998948 TI - A possible role for glyceraldehyde transport in the stimulation of HIT-T15 insulinoma cells. AB - D-Glyceraldehyde was transported into HIT-T15 cells at a linear rate for approx. 2 min and appeared to be unsaturable up to a concentration of 50 mM. Evidence was obtained for an electrogenic component of uptake of the triose. The rate of D glyceraldehyde transport was also reduced in the absence of Na+, suggesting that a component of uptake was Na(+)-linked. Transport of D-glyceraldehyde could be prevented by N-ethylmaleimide but not significantly by p chloromercuribenzenesulphonic acid, L-glyceraldehyde, nor by a number of inhibitors of known transport systems. However, D-glyceraldehyde transport was inhibited by alpha-cyano-4-hydroxycinnamate, an inhibitor of some anion transport systems. D-Glyceraldehyde caused a marked depolarization of HIT-T15 cells accompanied by a rise in cytosolic [Ca2+] and [Na+] and a gradual intracellular acidification. The glyceraldehyde-induced rise in cytosolic [Na+] and intracellular acidification, but not the depolarization or rise in cytosolic [Ca2+], were reduced by dithiothreitol and 5-aminoguanidine, compounds which form chemical adducts with alpha-ketoaldehydes. Incubation of HIT cells with either D- or L-glyceraldehyde resulted in the formation of large amounts of D-lactate, the end product of methylglyoxal metabolism via the glyoxalase pathway. It is suggested that the depolarizing action of glyceraldehyde is the result, at least in part, of its electrogenic transport, probably via Na(+)-coupled entry into HIT cells involving an unidentified transport system. The intracellular acidification and a component of the increase in cytosolic [Na+] may be largely due to the presence of one or more dicarbonyl contaminants in the glyceraldehyde preparation. PMID- 7998949 TI - Identification of rat liver phosphatidylinositol synthase as a 21 kDa protein. AB - Substantial purification of rat liver phosphatidylinositol (PtdIns) synthase has been achieved by a combination of Hecameg extraction, heat treatment, affinity chromatography and chromatography on PBE-94. The activity chromatographs as a single peak which has an apparent molecular mass between 150 and 200 kDa on Sepharose 4B. When analysed by SDS/PAGE, two major bands are seen. The enzyme activity is correlated with a protein band of 21 kDa. A second band, at 51 kDa, is eluted from a PBE-94 column slightly ahead of the activity. Manganese is an absolute requirement for stabilization of activity in the presence of detergent. The effect of manganese is optimal at 0.5 mM; magnesium at a concentration of 10 mM is only minimally effective. Substrate Kms are 1.3 mM and 9.5 microM for inositol and CDP-diacylglycerol respectively. The activity eluting from the PBE 94 column is purified 5000-fold over the post-mitochondrial supernatant. PMID- 7998951 TI - A stress-regulated protein, GRP58, a member of thioredoxin superfamily, is a carnitine palmitoyltransferase isoenzyme. AB - We recently noted the association of carnitine palmitoyltransferase (CPT) activity with a 54 kDa microsomal protein [Murthy and Pande (1993) Mol. Cell Biochem. 122, 133-138] that, based on amino-acid-sequence identity, seemed to be the protein previously described as a 'glucose-regulated protein-58' (GRP58), phosphoinositide-specific phospholipase C, hormone-induced protein-70, endoplasmic-reticulum protein-61 (ERp61), protein disulphide-isomerase, thiol protease, a protein affected in halothane anaesthesia and one that affects renal tubular functions and the transcriptional activation of the interferon-alpha inducible genes. To ascertain the catalytic identity of this protein unambiguously, we have expressed the corresponding cDNA transiently and stably in human kidney 293 cells as well as in HeLa cells. In each case we found that expression led to an increase in assayable and immunoreactive 54 kDa CPT activity, whereas the protein disulphide-isomerase activity was not increased. In vitro expression in a cell-free transcription and translation system led to the synthesis of a approximately 57 kDa (precursor) protein that was processed to a approximately 54 kDa (mature) protein when microsomes were present; in both these experiments again a large increase in CPT activity was seen. Thus the present data provide compelling evidence that the 54 kDa protein in question is a CPT isoenzyme. It remains to be seen now how the ability of this protein to interconvert acyl-CoA and acylcarnitine would relate to the diverse functions indicated for this protein in vivo. PMID- 7998950 TI - Expression of the liver-type glucose transporter (GLUT2) in 3T3-L1 adipocytes: analysis of the effects of insulin on subcellular distribution. AB - We have expressed the liver-type facilitative glucose transporter, GLUT2, in the insulin-sensitive 3T3-L1 adipocyte clonal cell line in an effort to address the importance of transporter isoform and cellular environment on the ability of insulin to mediate glucose-transporter translocation. Analysis of non differentiated fibroblastic cell clones transfected with the GLUT2 cDNA identified the presence of this isoform in several independent clones. These clones exhibited increased deoxyglucose and fructose transport rates compared with control cells. Upon differentiation, the fibroblastic clones selected for study achieved > 95% phenotypic conversion into adipocytes. Expression of the GLUT2 protein was maintained throughout the differentiation protocol. Subcellular fractionation revealed that in response to insulin, unlike the native GLUT4, GLUT2 protein did not undergo significant translocation to the plasma membrane; furthermore, the subcellular distribution of the expressed GLUT2 was quite distinct from that of the endogenous GLUT4. 3T3-L1 adipocytes expressing GLUT2 only exhibited a 2-fold increase in insulin-stimulated fructose uptake, further suggesting that GLUT2 does not undergo insulin-stimulated translocation. PMID- 7998952 TI - Identical regional mechanisms of intracellular free Ca2+ concentration increase during polarized agonist-evoked Ca2+ response in pancreatic acinar cells. AB - The initial increase of intracellular free Ca2+ concentration ([Ca2+]i) following agonist stimulation is spatially restricted to one pole of the cell, from where a wave of [Ca2+]i spreads across the cytosol. In the present study we have investigated the dynamic properties of the agonist-activated Ca(2+)-release mechanisms in different regions of the acinar cell and show that, during maximal agonist stimulation, the rate of [Ca2+]i increase at the secretory pole is identical with that recorded at the basal pole. Furthermore, the relationship between [Ca2+]i and the apparent rate of [Ca2+]i increase is similar in both regions of the cell. The data show that whereas the sensitivity to the Ca(2+) releasing agent is different in different regions of the cell, the process of [Ca2+]i increase, once triggered, will proceed in an identical fashion, irrespective of the area of the cell. PMID- 7998953 TI - The toxic milk mouse does have elevated hepatic metallothionein mRNA. PMID- 7998955 TI - Recombinant alpha-L-iduronidase: characterization of the purified enzyme and correction of mucopolysaccharidosis type I fibroblasts. AB - Mucopolysaccharidosis type I (MPS I, Hurler and Scheie syndromes) is an autosomal recessive lysosomal storage disorder that results from a deficiency of the hydrolase alpha-L-iduronidase (IDUA) which is involved in the lysosomal degradation of both heparan sulphate (HS) and dermatan sulphate (DS). Patients with MPS I store and excrete large amounts of partially degraded HS and DS. In order to evaluate enzyme replacement therapy for MPS I patients we have expressed human IDUA cDNA in Chinese Hamster Ovary (CHO)-K1 cells utilizing a plasmid vector that places the cDNA under the transcriptional control of the human polypeptide-chain-elongation factor I alpha gene promoter. A clonal cell-line that secreted recombinant IDUA in a precursor form at approximately 2.2 micrograms/10(6) cells per day was identified. This enzyme was shown to be endocytosed into cultured MPS I fibroblasts via mannose-6-phosphate receptors and to correct the storage phenotype of these cells by enabling the lysosomal digestion of accumulated sulphated glycosaminoglycans. The recombinant IDUA had on SDS/PAGE a molecular mass of 85 kDa and was processed to 74 kDa and smaller forms following its uptake by fibroblasts. Milligram quantities of the recombinant IDUA were immunopurified and the enzyme was shown to have pH optimum and kinetic parameters differing from those of the mature enzyme purified from human liver. The specific activity of the recombinant enzyme was shown to increase on dilution and on incubation with reducing agents. This was in contrast to the mature IDUA form (74 kDa) which did not have its activity stimulated by reducing agents or dilution. PMID- 7998954 TI - Lysophosphatidylcholine increases the secretion of cholesteryl ester-poor triacylglycerol-rich lipoproteins by CaCo-2 cells. AB - To address the effect of lysophosphatidylcholine on triacylglycerol transport in intestine, CaCo-2 cells, grown on semipermeable supports, were incubated with lysophosphatidylcholine solubilized in 1 mM taurocholate. [14C]Palmitoyllysophosphatidylcholine was readily taken up and incorporated predominantly into cellular phospholipids, particularly phosphatidylcholine. Twenty-five percent of the label was found in triacylglycerols. Compared with labelled cellular phospholipids, labelled triacylglycerols were preferentially secreted. Lysophosphatidylcholine caused a profound decrease in cholesteryl ester synthesis and secretion, whereas cellular triacylglycerol mass and triacylglycerol synthesis and secretion were increased. The effect was more pronounced with oleoyllysophosphatidylcholine than with either palmitoyl- or stearyl-lysophosphatidylcholine. Lysophosphatidylcholine increased the secretion of immunoreactive and newly-synthesized apoprotein B (apoB) without altering the rate of apoB synthesis. Thus, luminal lysophosphatidylcholine and/or its uptake decreases cholesterol esterification and secretion, but increases triacylglycerol synthesis and secretion, triacylglycerol mass accumulation and the secretion of apoB by CaCo-2 cells. PMID- 7998956 TI - Novel K(+)-channel-blocking toxins from the venom of the scorpion Centruroides limpidus limpidus Karsch. AB - Two novel toxins were purified from the venom of the Mexican scorpion Centruroides limpidus limpidus, using an immunoassay based on antibodies raised against noxiustoxin (NTX), a known K(+)-channel-blocker-peptide. The primary structure of C. l. limpidus toxin 1 was obtained by Edman degradation and was shown to be composed of 38 amino acid residues, containing six half-cystines. The first 36 residues of C. l. limpidus toxin 2 were also determined. Both toxins are capable of displacing the binding of radio-labelled NTX to rat brain synaptosomes with high affinity (about 100 pM). These toxins are capable of inhibiting transient K(+)-currents (resembling IA-type currents), in cultured rat cerebellar granule cells. About 50% of the peak currents are reduced by application of a 1.5 microM solution of toxins 1 and 2 The K+ current reduction is partially reversible, under washing but not voltage-dependent. Comparison of the primary structure of C. l. limpidus toxin 1 with other known toxins shows 74% identity with margatoxin, 64% with NTX, 51% with kaliotoxin, 39% with iberiotoxin, 37% with charybdotoxin and Lq2, and 29% with leirutoxin 1. The only invariant amino acids in all these toxins are the six cysteines, a glycine in position 26 and two lysines at positions 28 and 33, respectively. The relevance of these differences in terms of possible structure-function relationships is discussed. PMID- 7998957 TI - Thapsigargin-induced nuclear calcium signals in rat basophilic leukaemia cells. AB - By a confocal fluorescence microscope with an argon-ion laser (488 nm) and a He Cd laser (325 nm) we have studied thapsigargin-induced calcium signals in individual rat basophilic leukaemia (RBL-2H3) cells. In the presence or absence of external calcium ions, thapsigargin-induced calcium signals were transferred to the nucleus as well as to the cytoplasm of RBL-2H3 cells. The calcium signals were generally much stronger in the nucleus than in the cytoplasm. However, some of the RBL-2H3 cells had apparently reduced nuclear calcium signals. They had a basophil-like bilobed (multilobed) nucleus, although most RBL-2H3 cells had a mast-cell-like monolobed nucleus. In the cells with a bilobed nucleus, IgE receptor-mediated calcium signals were neither transferred to the nucleus nor to the cytoplasm. The results gave a new insight into the understanding of the mechanism of the nuclear calcium signals in RBL-2H3 cells. PMID- 7998959 TI - Binding characteristics of scavenger receptors on liver endothelial and Kupffer cells for modified low-density lipoproteins. AB - Previous studies showed that both endothelial and Kupffer cells contain specific recognition sites of oxidized low-density lipoprotein (OxLDL), in addition to recognition sites which recognize OxLDL and acetylated LDL (AcLDL). We have determined the binding characteristics of the recognition sites for OxLDL on Kupffer cells and endothelial cells (OxLDL-specific binding-site) in comparison to the recognition site for AcLDL on endothelial cells, which recognizes both AcLDL and OxLDL (Ac/OxLDL binding site). The capacity of Kupffer cells to bind OxLDL (Bmax. = 779 ng of 125I-OxLDL/mg of cell protein; Kd = 6 micrograms/ml) was comparable to the binding-capacity of endothelial cells (Bmax. = 803 ng of 125I OxLDL/mg of cell protein; Kd = 5 micrograms/ml). The effect of net charge of modified LDL on its affinity for the recognition sites on Kupffer and endothelial cells was evaluated using competition studies. The affinity of AcLDL for the Ac/OxLDL binding site was greatly increased from 460 micrograms/ml to 4 micrograms/ml with increasing extent of modification and thus net charge. The Ac/OxLDL binding-site on endothelial cells also displayed an increased affinity towards LDL with an increasing degree of oxidation. The affinity of OxLDL for the Ac/OxLDL binding-site appeared to be about 4-fold higher than that of AcLDL with a similar extent of modification. At higher degrees of oxidation of LDL, the affinity for the OxLDL-specific site on endothelial and Kupffer cells was also strongly enhanced; the OxLDL-specific binding-site possesses a higher affinity for mildly oxidized LDL as compared with the Ac/OxLDL binding-site. It is concluded that recognition of OxLDL by both the OxLDL-specific binding-site and the Ac/OxLDL binding-site on liver endothelial and Kupffer cells depends on the net negative charge of modified LDL. The similarity in binding pattern of these binding sites makes it likely that the newly described 95 kD OxLDL binding protein on Kupffer cells [Y. B. De Rijke and Th. J. C. van Berkel, J. Biol. Chem. (1994), 269, 824-827] contains a recognition site with similar structural elements as described earlier for scavenger receptors. PMID- 7998958 TI - Interaction of procollagen I and other collagens with colligin. AB - Colligin is a collagen-binding glycoprotein of molecular mass 46000 Da localized to the endoplasmic reticulum (ER) of diverse kinds of cells that produce collagen I. In order to help define its role in collagen biosynthesis and to study the interaction of colligin with procollagen I in detail, the binding characteristics of colligin purified from L6 myoblasts have been studied. A total of 3 mol were found to bind/mol of procollagen I, with a Kd of about 25 nM. Both pure and separated pro alpha 1(I) and procollagen alpha 2 (I) chains were able to compete with procollagen I for binding to colligin. However, colligin binds to pro alpha 2 (I) with higher affinity than to pro alpha 1 (I). To find if the binding activity of colligin was altered during purification, an assay to measure colligin binding to procollagen in crude myoblast cell extracts was developed. This procedure gave the same binding parameters as did the highly purified colligin. Among different collagen types, colligin was found to bind to collagen I and collagen IV, but not to collagen III. In order to examine whether glycosylation or phosphorylation of colligin were required for the binding of colligin to procollagen I and to obtain enough colligin for further studies, recombinant protein was produced in Escherichia coli. An immunoaffinity purification scheme was used to get virtually pure protein in milligram yields. Comparison of the recombinant colligin with that isolated from L6 myoblasts showed that both types existed in solution as monomers and dimers. In addition, both types of colligins showed identical properties with regard to their binding to procollagen I and the isolated pro alpha 1(I) and pro alpha 2(I) chains. Post translational modifications of colligin were thus not essential for binding to procollagen I. PMID- 7998960 TI - Divalent cations stabilize the conformation of plasma cell membrane glycoprotein PC-1 (alkaline phosphodiesterase I). AB - The plasma cell-membrane glycoprotein PC-1 is an ectoenzyme with alkaline phosphodiesterase I/5'-nucleotide phosphodiesterase (EC 3.1.4.1) and nucleotide pyrophosphatase (EC 3.6.1.9) activities. It contains sequence motifs which closely match the consensus EF-hand (helix-loop-helix) Ca(2+)-binding regions of parvalbumin, troponin-C and calmodulin, and its enzymic activity is increased in the presence of divalent cations and decreased in the presence of chelating agents. We have undertaken experiments to determine whether divalent cations affect the conformation of the PC-1 protein, as assessed by their effect on thermal stability, resistance to proteolysis and binding of polyclonal antibodies to the whole native protein and monoclonal antibodies to a putative Ca(2+) binding region. Divalent cations were found to protect solubilized PC-1 against thermal denaturation and proteolysis. They also stabilized PC-1 on intact cells; this form was much more resistant to proteolysis than Triton X-100 solubilized PC 1. Ca2+, Mg2+ and Zn2+ ions were equally effective. Monoclonal antibodies to the bacterially expressed C-terminal EF-hand homology region only bound to mammalian PC-1 in the absence of Ca2+. In contrast, the great majority of polyclonal antibodies to native PC-1 bound regardless of whether Ca2+ was present or not, but with increased binding when Ca2+ was present. These results provide evidence that divalent cations bind to PC-1 and stabilize its conformation. PMID- 7998961 TI - Multiple effects of haemin binding on protease susceptibility of bovine serum albumin and a novel isolation procedure for its large fragment. AB - The effects of ligand binding on the proteolytic susceptibility of BSA were investigated. The rate for proteolytic digestion with either trypsin or chymotrypsin decreased in the presence of bilirubin and fatty acids, suggesting that overall albumin conformation is stabilized by these ligands. In contrast, haemin showed multiple effects on a proteolytic digestion pattern: the rate for the degradation of intact albumin greatly increased, but a large 45 kDa fragment accumulated during proteolytic digestion in the presence of this ligand. This unique fragmentation pattern allowed us to isolate the 45 kDa fragment at a high yield (about 30% on a molar basis) by one-step purification. Sequence analyses indicated that this fragment lies between residues Thr190 and Ala583, which constitutes domains II and III of the albumin molecule. Far-u.v. c.d. spectra strongly suggested that the secondary structure in the intact albumin is almost retained in the 45 kDa fragment. The isolated 45 kDa fragment showed haemin binding ability, as evaluated by spectroscopic titration; upon re-digestion of the 45 kDa fragment, haemin showed strong protective effects. These results were consistent with the idea that haemin binding to BSA induces an increased protease susceptibility in the loop region between domains I and II, but in the overall conformation of domains II and III, a protease-resistant property. PMID- 7998962 TI - Constitutive nuclear NF-kappa B in cells of the monocyte lineage. AB - In monocytes, the nuclear factor NF-kappa B has been invoked as an important transcription factor in the expression of cytokine genes, of cell-surface receptors and in the expression of human immunodeficiency virus. In such cells, DNA binding activity of NF-kappa B can be detected without intentional stimulation. In our studies, cells of the human monocytic line Mono Mac 6, cultured in medium containing fetal-calf serum and low levels of lipopolysaccharide (LPS), also exhibit such 'constitutive' NF-kappa B, as demonstrated by mobility-shift analysis of nuclear extracts. This nuclear NF kappa B was still present when contaminant LPS was removed by ultrafiltration and when serum was omitted. Protein-DNA complexes of constitutive NF-kappa B are similar in mobility to the LPS-induced NF-kappa B and both are recognized by an antibody specific to the p50 subunit of NF-kappa B. By contrast, treatment of cells with pyrrolidine dithiocarbamate (PDTC) will only block LPS-induced NF kappa B, but not the constitutive binding protein. Using LPS-free and serum-free conditions, constitutive NF-kappa B can be detected in different cell lines of the monocytic lineage (HL60, U937, THP-1, Mono Mac 1 and Mono Mac 6), but not in Molt 4 T cells or K562 stem cells. When ordered according to stage of maturation, the amount of constitutive NF-kappa B was not increased in more mature cell lines. Furthermore, when inducing differentiation in Mono Mac 6 cells, with vitamin D3, no change in constitutive or inducible NF-kappa B can be detected. Analysis of primary cells revealed substantial constitutive NF-kappa B-binding activity in blood monocytes, pleural macrophages and alveolar macrophages. The constitutive NF-kappa B appears to be functionally active, since a low level of tumour necrosis factor (TNF) transcript is detectable in monocytes, and this level can be increased by blocking transcript degradation using cycloheximide. The level of constitutive NF-kappa B in these cells is variable and is frequently found to be lower in the more mature macrophages. Constitutive NF-kappa B was not maintained by autocrine action of cytokines TNF, interleukin 6, interleukin 10, granulocyte-macrophage colony-stimulating factor or macrophage colony-stimulating factor, since neutralizing antibodies did not reduce constitutive DNA-binding activity. Furthermore, blockade of prostaglandin or leukotriene biosynthesis did not affect constitutive NF-kappa B.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 7998963 TI - Structural comparisons lead to the definition of a new superfamily of NAD(P)(H) accepting oxidoreductases: the single-domain reductases/epimerases/dehydrogenases (the 'RED' family). AB - Using both primary- and tertiary-structure comparisons, we have established new structural similarities shared by reductases, epimerases and dehydrogenases not previously known to be related. Despite the low sequence identity (down to 10%), short consensus segments are identified. We show that the sequence, the active site and the supersecondary structure are well conserved in these proteins. New homologues (the protochlorophyllide reductases) are detected, and we define a new superfamily composed of single-domain dinucleotide-binding enzymes. Rules for the cofactor-binding specificity are deduced from our sequence alignment. The involvement of some amino acids in catalysis is discussed. Comparison with two domain dehydrogenases allows us to distinguish two general mechanisms of divergent evolution. PMID- 7998965 TI - Transforming growth factor-beta 1 inhibits casein secretion from differentiating mammary-gland explants but not from lactating mammary cells. AB - Transforming growth factor-beta (TGF beta) is important in the maturation and function of the mammary gland and is present in milk. We have examined whether, in addition to inhibiting lactogenesis, TGF beta exerts acute regulatory effects on lactating mammary cells. The isoform TGF beta 1 at 5 and 50 ng/ml suppressed the onset of lactation and the subsequent production of beta-casein by differentiating mouse mammary explants from pregnant mice. By contrast, it did not inhibit protein synthesis or secretion from acini isolated from lactating mouse mammary gland or protein secretion from explants from lactating mice. These data indicate that TGF beta inhibits the onset of casein secretion, but is not an acute regulator of casein synthesis or secretion from differentiated lactating mammary cells. PMID- 7998966 TI - Human blood cells support the reduction of low-density-lipoprotein-associated cholesteryl ester hydroperoxides by albumin-bound ebselen. AB - Ebselen, a glutathione peroxidase mimic capable of reducing simple as well as complex hydroperoxides, including those of phospholipids and cholesteryl esters in intact oxidized low-density lipoprotein (LDLox), requires the presence of low molecular-mass thiols to be active. In plasma, the drug is thought to be transported as an inactive albumin complex. As formation of LDLox is likely to occur extracellularly, we tested under which conditions ebselen can support reduction of LDLox-associated cholesteryl ester hydroperoxides outside cells. We observed that addition of albumin-bound ebselen to whole blood, but not plasma, resulted in reduction of LDLox-associated cholesteryl linoleate hydroperoxides to the corresponding hydroxides. The observed reduction was rapid and its extent increased with increasing concentrations of ebselen. Physical contact of blood cells with LDLox was not required for this reducing activity. These results demonstrate that, in the presence of blood cells, extracellular ebselen is catalytically active. They suggest that ebselen may be considered as a drug for extracellular targets. PMID- 7998964 TI - Expression and functional properties of fumarate reductase. PMID- 7998967 TI - Neutrophil collagenase (MMP-8) cleaves at the aggrecanase site E373-A374 in the interglobular domain of cartilage aggrecan. AB - Native and recombinant neutrophil collagenase (MMP-8) was shown to cleave at the E373-A374 'aggrecanase' site in the interglobular domain of aggrecan. The time course of digestion in vitro showed that MMP-8 cleaved initially at N341-F342, the predominant metalloproteinase site, before cleaving at the E373-A374 site. A synthetic peptide, IPENFFG, inhibited cleavage at E373-A374 but not N341-F342 in vitro, indicating that the E373-A374 sequence was a less preferred site for MMP-8 cleavage than N341-F342. IPENFFG also inhibited release of A374 RGSVI fragments from cartilage in explant culture, suggesting that a metalloproteinase cleaved at the aggrecanase site in situ. The possibility remains that 'aggrecanase' may be a metalloproteinase in cartilage. PMID- 7998968 TI - The turkey erythrocyte beta-adrenergic receptor couples to both adenylate cyclase and phospholipase C via distinct G-protein alpha subunits. AB - By contrast with mammalian beta-adrenergic receptors, the avian isoform elicits two distinct effector responses, activation of adenylate cyclase and polyphosphoinositide-specific phospholipase C (PLC) leading to the accumulation of both cyclic adenosine monophosphate (cyclic AMP) and inositol phosphates. We have investigated the mechanisms of beta-adrenergic receptor signalling in turkey erythrocytes. Stimulation of adenylate cyclase by the beta-adrenergic-receptor agonist isoprenaline exhibits a 30-fold lower EC50 than that for PLC activation, which may indicate a marked receptor reserve for the former effector. Similar Ki values were obtained for the inhibition of both responses by four beta-adrenergic antagonists, arguing that a single receptor population is responsible for both effects. Antibodies raised against G-protein peptide sequences were used to show that the identity of the G-protein mediating the PLC response was an avian homologue of G11, the level of expression of which was very similar to that of the stimulatory G-protein of adenylate cyclase, Gs. Thus a single population of beta-adrenergic receptors apparently interacts with distinct G-proteins to activate different effectors. The stoichiometries of the receptor-G-protein effector interactions are therefore similar for both second-messenger responses and the data are discussed in terms of the different efficacies observed for each response. PMID- 7998970 TI - Secondary structure of neutrophil-activating peptide-2 determined by 1H-nuclear magnetic resonance spectroscopy. AB - Neutrophil-activating protein-2 (NAP-2) is a 72 residue protein demonstrating a range of proinflammatory activities. The solution structure of monomeric NAP-2 has been investigated by two-dimensional 1H-n.m.r. spectroscopy. Sequence specific proton resonance assignments have been made and secondary structural elements have been identified on the basis of nuclear Overhauser data, coupling constants and amide hydrogen/deuteron exchange. The NAP-2 monomer consists of a triple-stranded anti-parallel beta-sheet arranged in a 'Greek key' and a C terminal helix (residues 59-70) and is very similar to that found in the n.m.r. solution conformation of dimeric interleukin-8 and the crystal structure of tetrameric bovine platelet factor-4. Results are discussed in terms of heparin binding and neutrophil-activation properties of NAP-2. PMID- 7998969 TI - Calpastatin in erythrocytes of young and old individuals. AB - To gain knowledge about the behaviour of calpastatin (the specific inhibitor of the Ca(2+)-dependent thiol protease calpain) in the intact cell, we analysed the inhibitor by specific antibodies and determined its activity in erythrocytes from individuals 20-34 years old (young) and 70-93 years old (old). Differences between old and young in the behaviour of erythrocyte calpastatin were observed. Erythrocytes of old individuals had lower amounts of calpastatin and less calpastatin activity than those of young ones. A difference between old and young was also found in the molecular-mass distribution of calpastatin subunits. Increasing the erythrocyte Ca2+ induced changes in calpastatin in young individuals, rendering it similar to calpastatin in cells of old individuals. When calpastatin (isolated from erythrocytes of a young individual) was added to erythrocyte membranes, the initial binding and subsequent association of calpastatin with the membrane were lower in old than in young individuals. We had previously found that calpain binding and activation were enhanced in erythrocyte membranes from old individuals, along with enhanced degradation of band 3 (a major erythrocyte transmembrane anion-transport protein). The overall results indicate an interaction of calpain with calpastatin in the intact cell. Enhanced activation of erythrocyte calpain and degradation of calpastatin occur under conditions of increased cellular Ca2+ and in cells of the aged. PMID- 7998972 TI - Purification of NADPH-dependent dehydroascorbate reductase from rat liver and its identification with 3 alpha-hydroxysteroid dehydrogenase. AB - Rat liver cytosol has been found to reduce dehydroascorbic acid (DHAA) to ascorbic acid in the presence of NADPH. The enzyme responsible for such activity has been purified by ammonium sulphate fractionation, DEAE-Sepharose, Sephadex G 100 SF and Reactive Red column chromatography, with an overall recovery of 27%. SDS/PAGE of the purified enzyme showed one single protein band with an M(r) of 37,500. A similar value (36,800) was found by gel filtration on a Sephadex G-100 SF column. The results indicate that the enzyme is a homogeneous monomer. The Km for DHAA was 4.6 mM and the Vmax. was 1.55 units/mg of protein; for NADPH Km and Vmax. were 4.3 microM and 1.10 units/mg of protein respectively. The optimum pH was around 6.2. Several typical substrates and inhibitors of the aldo-keto reductase superfamily have been tested. The strong inhibition of DHAA reductase effected by steroidal and non-steroidal anti-inflammatory drugs, together with the ability to reduce 5 alpha-androstane-3,17-dione strongly, suggest the possibility that DHAA reductase corresponds to 3 alpha-hydroxysteroid dehydrogenase. Microsequence analysis performed on the electro-transferred enzyme band shows that the N-terminus is blocked. Internal primary structure data were obtained from CNBr-derived fragments and definitely proved the identity of NADPH dependent DHAA reductase with 3 alpha-hydroxysteroid dehydrogenase. PMID- 7998971 TI - Mastoparan may activate GTP hydrolysis by Gi-proteins in HL-60 membranes indirectly through interaction with nucleoside diphosphate kinase. AB - The wasp venom, mastoparan (MP), activates reconstituted pertussis toxin (PTX) sensitive G-proteins in a receptor-independent manner. We studied the effects of MP and its analogue, mastoparan 7 (MP 7), on G-protein activation in HL-60 cells and a reconstituted system and on nucleoside diphosphate kinase (NDPK)-catalysed GTP formation. MP activated high-affinity GTP hydrolysis in HL-60 membranes with an EC50 of 1-2 microM and a maximum at 10 microM. Unlike the effects of the formyl peptide receptor agonist, N-formyl-L-methionyl-L-leucyl-L-phenylalanine (fMet-Leu-Phe), on GTPase, those of MP were only partially PTX-sensitive. MP induced rises in cytosolic Ca2+ concentration and superoxide-anion formation in intact HL-60 cells were also only incompletely PTX-sensitive. N-Ethylmaleimide inhibited MP-stimulated GTP hydrolysis to a greater extent than that stimulated by fMet-Leu-Phe. Unlike the latter, MP did not enhance incorporation of GTP azidoanilide into, and cholera toxin-catalysed ADP-ribosylation of, Gi-protein alpha-subunits in HL-60 membranes. By contrast to fMet-Leu-Phe, MP did not or only weakly stimulated binding of guanosine 5'-[gamma-thio]triphosphate to Gi protein alpha-subunits. MP 7 was considerably more effective than MP at activating the GTPase of reconstituted Gi/G(o)-proteins, whereas in HL-60 membranes, MP and MP 7 were similarly effective. MP and MP 7 were similarly effective at activating [3H]GTP formation from [3H]GDP and GTP in HL-60 membranes and by NDPK purified from bovine liver mitochondria. Our data suggest the following: (1) MP activates Gi-proteins in HL-60 cells, but (2) the venom does not simply mimic receptor activation. (3) MP and MP 7 may activate GTP hydrolysis in HL-60 membranes indirectly through interaction with NDPK. (4) MP 7 is a more effective direct activator of PTX-sensitive G-proteins than MP, whereas with regard to NDPK, MP and MP 7 are similarly effective. PMID- 7998974 TI - Identification of two splice variant forms of type-IVB cyclic AMP phosphodiesterase, DPD (rPDE-IVB1) and PDE-4 (rPDE-IVB2) in brain: selective localization in membrane and cytosolic compartments and differential expression in various brain regions. AB - In order to detect the two splice variant forms of type-IVB cyclic AMP phosphodiesterase (PDE) activity, DPD (type-IVB1) and PDE-4 (type-IVB2), anti peptide antisera were generated. One set ('DPD/PDE-4-common'), generated against a peptide sequence found at the common C-terminus of these two PDEs, detected both PDEs. A second set was PDE-4 specific, being directed against a peptide sequence found within the unique N-terminal region of PDE-4. In brain, DPD was found exclusively in the cytosol and PDE-4 exclusively associated with membranes. Both brain DPD and PDE-4 activities, isolated by immunoprecipitation, were cyclic AMP-specific (KmcyclicAMP: approximately 5 microM for DPD; approximately 4 microM for PDE-4) and were inhibited by low rolipram concentrations (K1rolipram approximately 1 microM for both). Transient expression of DPD in COS-1 cells allowed identification of an approx. 64 kDa species which co-migrated on SDS/PAGE with the immunoreactive species identified in both brain cytosol and membrane fractions using the DPD/PDE-4-common antisera. The subunit size observed for PDE 4 (approx. 64 kDa) in brain membranes was similar to that predicted from the cDNA sequence, but that observed for DPD was approx. 4 kDa greater. Type-IV, rolipram inhibited PDE activity was found in all brain regions except the pituitary, where it formed between 30 and 70% of the PDE activity in membrane and cytosolic fractions when assayed with 1 microM cyclic AMP, PDE-4 formed 40-50% of the membrane type-IV activity in all brain regions save the midbrain (approx. 20%). DPD distribution was highly restricted to certain regions, providing approx. 35% of the type-IV cytosolic activity in hippocampus and 13-21% in cortex, hypothalamus and striatum with no presence in brain stem, cerebellum, midbrain and pituitary. The combined type-IVB PDE activities of DPD and PDE-4 contributed approx. 10% of the total PDE activity in most brain regions except for the pituitary (zero) and the mid-brain (approx. 3%. The isolated cDNAs for DPD and PDE-4 appear to reflect transcription products which are expressed in vivo in brain. The unique N-terminal domain of PDE-4 is suggested to target this PDE to membranes in brain. Type-IVB PDEs are differentially expressed in various brain regions, indicating that there are tissue-specific controls on both the expression of the gene and the splicing of its products. PMID- 7998973 TI - Analysis of the rat lactate dehydrogenase A subunit gene promoter/regulatory region. AB - The rat lactate dehydrogenase (LDH) A subunit gene promoter contains a putative AP-1 binding site at -295/-289 bp, two consensus Sp1 binding sites at -141/-136 bp and -103/-98 bp, and a single copy of a consensus cyclic AMP-responsive element (CRE) at -48 to -41 bp upstream of the transcription initiation site. Additionally, an as yet unidentified silencer element is located within the 1173/-830 bp 5'-flanking region. Transient transfection analyses of a -1173/+25 bp LDH A-chLoramphenicol acetyltransferase fusion gene has indicated a complete inability of the promoter fragment to direct basal or forskolin-induced transcription. Deletion of the -1173/-830 bp sequence restored basal and cyclic AMP (cAMP)-inducible activity. Point mutations in the Sp1 binding sites of a 830/+25 bp promoter fragment reduced basal but not the relative degree of cAMP inducible activity. cAMP-regulated transcriptional activity was dependent upon an 8 bp CRE, -TGACGTCA-, located at the -48/-41 bp upstream region. Mutations in the CRE abolished cAMP-mediated induction and reduced basal activity by about 65%. The CRE binds a 47 kDa protein which has previously been identified as CRE binding protein (CREB)-327, an isoform of the activating transcription factor/CREB transcription factor gene family. Co-transfection of a vector that expresses the catalytic subunit of cAMP-dependent protein kinase stimulates LDH A subunit promoter activity suggesting that cAMP induces LDH A subunit gene expression through phosphorylative modification of CREB-327. This study emphasizes a fundamental role of several modules including Sp1 and CREB binding sites in regulating basal and cAMP-mediated transcriptional activity of the LDH A gene. PMID- 7998975 TI - Cytosolic phospholipase A2 gene expression in rat mesangial cells is regulated post-transcriptionally. AB - Cytosolic phospholipase A2 (cPLA2) is thought to be the rate-limiting enzyme in the arachidonic acid/eicosanoid cascade. The ability of various agonists to increase steady-state cPLA2 mRNA levels has previously been reported. The current study delineates the contributions of transcriptional and post-transcriptional processes to the regulation of cPLA2 gene expression in response to a variety of agonists in cultured rat glomerular mesangial cells. Epidermal growth factor, platelet-derived growth factor, serum and phorbol myristate acetate all increase the half-life of cPLA2 mRNA transcripts, indicating a role for post transcriptional modulation of gene expression. The presence of three ATTTA motifs in the 3' untranslated region (3'UTR) of the rat cPLA2 cDNA is ascertained. Heterologous expression of chimeric constructs with different 3'UTRs ligated into the 3' end of the luciferase coding region reveals that the presence of the cPLA2 3'UTR results in reduced luciferase activity compared with constructs without the cPLA2 3'UTR. Furthermore, the luciferase activity in the constructs with the cPLA2 3'UTR is increased in response to the same agonists which stabilize endogenous cPLA2 mRNA. A negligible effect of these agonists on transcriptional control of cPLA2 is evident using promoter-reporter constructs expressed in transient and stable transfectants. Taken together, these results indicate predominant post-transcriptional regulation of cPLA2 mRNA levels. PMID- 7998976 TI - Effect of unesterified cholesterol on the activity of cholesteryl ester transfer protein. AB - Cholesteryl ester transfer protein (CETP) catalyses the transfer of cholesteryl ester from high-density lipoprotein to triacylglycerol-rich lipoproteins and the transfer of triacylglycerols in the reverse direction. The activity of CETP has been studied using a continuous fluorescence assay which measures the excimer fluorescence of cholesteryl 1-pyrene decanoate in a synthetic donor microemulsion as the indicator of cholesteryl ester transfer. Emulsions were composed of cholesteryl oleate and egg phosphatidylcholine and had an average particle size of 14 +/- 1 nm as calculated from the molar volume of the components. The effect of changing the physical state of the emulsion surface was examined by including unesterified cholesterol in the donor and acceptor particles. The rate of CETP induced transfer of the fluorescent cholesteryl ester between microemulsion particles increased when unesterified cholesterol was present at concentrations up to 17 mol% relative to phospholipid. The presence of cholesterol also changed the exchange kinetics from an apparent single-exponential to a double-exponential phenomenon. Binding of CETP to the emulsion surface was accompanied by an enhancement of fluorescence which was used to measure the binding equilibria. The enhancement of exchange due to the presence of cholesterol did not correlate with any increased binding of CETP to the emulsion surface. The presence of unesterified cholesterol in the donor did not affect the rate of transfer of the fluorescent cholesteryl ester when unlabelled emulsion was replaced by high density lipoprotein as the acceptor. The studies demonstrate the use of microemulsions of defined size and composition for the study of the mechanism of action of CETP. PMID- 7998978 TI - Electronic properties of the dissimilatory sulphite reductase from Desulfovibrio vulgaris (Hildenborough): comparative studies of optical spectra and relative reduction potentials for the [Fe4S4]-sirohaem prosthetic centres. AB - The dissimilatory sulphite reductase (desulfoviridin) from the sulphate-reducing bacterium Desulfovibrio vulgaris (Hildenborough) displays distinct optical and redox characteristics relative to the haem subunit of Escherichia coli assimilatory sulphite reductase. For high-spin pentaco-ordinate desulfoviridin there is minimal change in the absorbance of the oxidized chromophores both after reduction or after addition of exogenous ligands. A ligand-metal charge-transfer band approximately 702 nm is observed in both the oxidized and one-electron reduced enzyme. E.p.r. spectroscopy has been used to define the relative reduction potentials for sirohaem and [Fe4S4] centres (delta E0 = Es0-Ec0) as a function of sirohaem axial co-ordination. Typically delta E0 lies in a range from -10 to -50 mV. These results show a correlation with the sigma-donor or pi acceptor properties of the ligand and stand in sharp contrast with estimates for the E. coli enzyme. The electronic properties of the coupled [Fe4S4]-sirohaem redox centre common to both nitrite- and sulphite-reducing enzymes are apparently strongly dependent on the environment generated by protein side chains. PMID- 7998977 TI - Antigen and thapsigargin promote influx of Ca2+ in rat basophilic RBL-2H3 cells by ostensibly similar mechanisms that allow filling of inositol 1,4,5 trisphosphate-sensitive and mitochondrial Ca2+ stores. AB - In single, Fura 2-loaded RBL-2H3 cells, antigen and thapsigargin depleted the same intracellular pool of Ca2+ in the absence of external Ca2+; provision of external Ca2+ induced immediate increases in levels of free Ca2+ ([Ca2+]i). These increases were dependent on the presence of external Ca2+ and, presumably, on influx of Ca2+ across the cell membrane. Both stimulants enhanced intracellular accumulation of 45Ca2+ through ostensibly similar mechanisms because accumulation was blocked to similar extents by various multivalent cations or by depolarization with K+. Because thapsigargin blocked reuptake of Ca2+ into inositol 1,4,5-trisphosphate sensitive stores, uptake occurred independently of the refilling of these stores. Uptake was dependent instead on sequestration of 45Ca2+ in a pool of high capacity that was insensitive to thapsigargin, caffeine, GTP and inositol 1,4,5-trisphosphate but sensitive to ionomycin and mitochondrial inhibitors. The existence of an inositol 1,4,5-trisphosphate-insensitive pool was also apparent in permeabilized cells; at 0.1 microM [Ca2+]i, uptake of 45Ca2+ was largely confined (> 80%) to the inositol 1,4,5-trisphosphate-sensitive pool, but at 2 microM [Ca2+]i uptake was largely (> 60%) into the inositol 1,4,5 trisphosphate-insensitive pool. Provision of mitochondrial inhibitors along with thapsigargin to block uptake into both pools, did not impair the thapsigargin induced increase in [Ca2+]i or influx of Ca2+, as indicated by changes in Fura 2 fluorescence, but did block the intracellular accumulation of 45Ca2+. The studies illustrate the utility of simultaneous measurements of [Ca2+]i and 45Ca2+ uptake for a full accounting of Ca2+ homoeostasis as exemplified by the ability to distinguish between influx and mitochondrial uptake of Ca2+. PMID- 7998979 TI - Amylin impairment of insulin effects on glycogen synthesis and phosphoenolpyruvate carboxykinase gene expression in rat primary cultured hepatocytes. AB - The ability of amylin to impair hepatic insulin action is controversial. We have found that the effect of amylin in primary cultured hepatocytes is strongly dependent on the culture conditions. Only in hepatocytes preincubated in the presence of fetal serum did amylin, at concentrations ranging from 1 to 100 nM, reduce insulin-stimulated glycogen synthesis rate and glycogen accumulation without showing direct effects. Neither basal glycogen synthase nor glycogen phosphorylase activity was modified by amylin treatment. Nevertheless, amylin (100 nM) blocked the activation of glycogen synthase by insulin. Amylin also proved capable of opposing the reduction in the expression of the phosphoenolpyruvate carboxykinase (PEPCK) gene induced by insulin, whereas the basal mRNA level of PEPCK was unaffected by amylin treatment. Thus, these results show that, in cultured rat hepatocytes, amylin is indeed able to interfere with insulin regulation of glycogenesis and PEPCK gene expression, favouring the hypothesis that amylin may modulate liver sensitivity to insulin. PMID- 7998980 TI - Binding of human collectins (SP-A and MBP) to influenza virus. AB - Collectins are a group of soluble proteins each of which has collagenous domains and non-collagenous globular domains, the latter containing the consensus residues found in C-type lectins. Members of the collectin family are the serum proteins mannan-binding protein (MBP), conglutinin, CL-43, and the lung associated proteins surfactant protein A (SP-A) and surfactant protein D (SP-D). MBP and conglutinin have been shown previously to bind to influenza viruses and to inhibit the infectivity and haemagglutinating activity of influenza viruses. We report here that the lung protein SP-A, like MBP, can bind to influenza virus (strain A/X31) through its lectin domain and inhibit the virus-mediated agglutination of red cells. The binding of SP-A or MBP to influenza virus was saturable, concentration-dependent, and required the presence of Ca2+ ions. Ligand-blot analysis, using MBP as ligand, of the virus lysate indicated that MBP binds to a 68 kDa viral species. The 68 kDa species was isolated to homogeneity and was shown to be the viral neuraminidase. The purified 68 kDa species inhibited the binding of both MBP and SP-A to influenza virus. PMID- 7998981 TI - Alternative pathways for phosphatidylcholine synthesis in olive (Olea europaea L.) callus cultures. AB - Olive (Olea europaea L.) callus cultures were incubated with [2-14C]ethanolamine and [Me-14C]choline in order to study phospholipid synthesis. Radioactivity from [Me-14C]choline was shown to be incorporated into the phosphatidylcholine via the CDP-base pathway. [2-14C]Ethanolamine was primarily incorporated into phosphatidylethanolamine, but significant radio-activity was also detected in phosphatidylcholine, indicating the operation of a methylation route. Incubation with [2-14C]ethanolamine indicated that phosphatidylcholine and phosphatidylethanolamine incorporated radiolabel over a similar time course. This led us to investigate the possibility that phosphatidylcholine was being synthesized by a methylation pathway distinct from the direct methylation of phosphatidylethanolamine. There was extensive incorporation of [2 14C]ethanolamine into different components of the aqueous phase of the incubations, within which phospho-base derivatives of ethanolamine were prominent. These intermediates were identified and provided evidence for the operation of an alternative methylation pathway via phosphodimethylethanolamine for the biosynthesis of phosphatidylcholine in olives. PMID- 7998982 TI - Histamine-induced Ca2+ entry precedes Ca2+ mobilization in bovine adrenal chromaffin cells. AB - The relationship between histamine-induced Ca2+ mobilization and Ca2+ entry in bovine adrenal chromaffin cells has been investigated. Stopped-flow fluorimetry of fura-2-loaded chromaffin cell populations revealed that 10 microM histamine promoted entry of Ca2+ or Mn2+ without measurable delay (< or = 20 ms), through a pathway that was insensitive to the dihydropyridine antagonist nifedipine. In the absence of extracellular Ca2+, or in the presence of 100 microM La3+, a blocker of receptor-mediated Ca2+ entry, 10 microM histamine triggered an elevation in intracellular calcium concentration ([Ca2+]i), but only after a delay of approx. 200 ms, which presumably represented the time required to mobilize intracellular Ca2+. These data suggested that histamine-induced bivalent-cation entry precedes extensive Ca2+ mobilization in chromaffin cells. In order to confirm that histamine can promote Ca2+ entry largely independently of mobilizing intracellular Ca2+, the ability of histamine to promote Ca2+ entry into cells whose intracellular Ca2+ store had been largely depleted was assessed. Fura-2 loaded chromaffin cells were treated with 10 microM ryanodine together with 40 mM caffeine, to deplete the hormone-sensitive Ca2+ store. This resulted in an approx. 95% inhibition of histamine-induced Ca2+ release. Under these conditions, histamine was still able to promote an entry of Ca2+ that was essentially indistinguishable from that promoted in control cells. In single cells, introduction of heparin (100 mg/ml), but not de-N-sulphated heparin (100 mg/ml), abolished the histamine-induced rise in [Ca2+]i. All these data suggest that histamine can induce G-protein- or inositol phosphate-dependent rapid (< or = 20 ms) Ca2+ entry without an extensive intracellular mobilization response in chromaffin cells, which points to activation of an entry mechanism distinct from the Ca(2+)-release-activated Ca2+ channel found in non-excitable cells. PMID- 7998984 TI - Guanosine 5'-[gamma-thio]triphosphate induces membrane localization of cytosol independent phospholipase D activity in a cell-free system from U937 promonocytic leucocytes. AB - Activation of phospholipase D (PLD) in phagocytic leucocytes requires protein components present in both the plasma membrane and the cytosol, but the catalytic and regulatory factors are not fully defined. We have characterized the effect of guanosine 5'-[gamma-thio]triphosphate (GTP[S]) on the subcellular requirements for reconstitution of PLD activity, using a cell-free system from U937 human promonocytic leucocytes. Incubation of permeabilized cells with 100 microM GTP[S] resulted in a membrane-localized PLD activity which was independent of added cytosol. The PLD activity of membranes from GTP[S]-treated cells was 7-fold greater than the basal activity of control membranes, and could be further augmented by the addition of ATP. This was the first demonstration of a stable agonist-regulated PLD activity in membranes from phagocytic leucocytes which was quantitatively comparable with that seen in a fully reconstituted system. Cytosol from GTP[S]-treated cells had a decreased capacity to support PLD activation, consistent with GTP[S]-induced depletion of a factor essential for reconstitution of PLD activity. Incubation of isolated membrane and cytosol with GTP[S] also resulted in a cytosol-independent PLD activity in the re-isolated membranes. The effect of GTP[S] could be mimicked by guanosine 5'-[beta gamma imido]triphosphate, but not by aluminium fluoride, consistent with the involvement of a low-molecular-mass GTP-binding protein(s). Incubation of isolated subcellular fractions with GTP[S], followed by removal of unbound nucleotide, suggested that at least one of the GTP-binding proteins involved in the membrane localization of PLD activity was itself present in the membrane fraction. These data were consistent with a model in which activation of GTP binding protein(s) resulted in the stable assembly of an active PLD signalling complex at the membrane surface. PMID- 7998985 TI - Structural heterogeneity of Pseudomonas aeruginosa bacterioferritin. AB - The subunit composition, amino acid sequence and haem-binding characteristics of bacterioferritin (BFR) from Pseudomonas aeruginosa have been studied. Unlike other BFRs, P. aeruginosa BFR was found to contain two subunit types, designated alpha and beta, which differed considerably in their amino acid sequences. The N terminal 69 and 55 amino acids of the alpha and beta subunits respectively were determined. The alpha subunit differed most from other BFRs. The two subunits were present in variable proportions in different preparations. The maximum stoichiometry of haem binding was found to be sample-dependent and to be different from the previously reported one per subunit [Kadir and Moore (1990) FEBS Lett. 271, 141-143]. This previous haem-binding study was shown to have been carried out with damaged protein, which contained both normal alpha and beta subunits and shorter versions of these that appeared to have been produced by cleavage of the normal subunits. The possibility that aging processes degrade ferritins and affect their haem-binding characteristics is discussed. PMID- 7998983 TI - Mechanisms of endotoxin-induced haem oxygenase mRNA accumulation in mouse liver: synergism by glutathione depletion and protection by N-acetylcysteine. AB - In in vitro systems haem oxygenase-1 (HO-1) mRNA increases after exposure to agents causing oxidative stress. We lowered cellular antioxidant defence systems in vivo by giving mice increasing doses (0.15 g/kg-1.6 g/kg) of DL-buthionine (S,R)-sulphoximine (BSO), a specific inhibitor of glutathione synthesis. Maximum glutathione depletion (80%) coincided with maximum hepatic HO-1 mRNA accumulation (about 20 times), whereas with 50% depletion, accumulation was only doubled. It has been suggested that reactive oxygen and nitrogen intermediates are involved in hepatic toxicity of endotoxin (lipopolysaccharide, LPS); LPS even at low doses [0.1 mg/kg, intraperitoneally (i.p.)] induces HO-1 mRNA about 25-fold after 1 h. Hepatic glutathione depletion (respectively 40% and 80%) after a low (0.3 g/kg) or a high (1.6 g/kg) BSO dose, resulted in potentiation of the HO-1 mRNA accumulation induced by LPS (0.1 mg/kg, i.p.). In the absence of BSO, N acetylcysteine (NAC) (1 g/kg orally) reduced LPS-induced HO-1 mRNA accumulation to one fourth. Under the same experimental conditions S-adenosylmethionine (SAM) was not effective. NAC also reduced HO-1 mRNA accumulation when administered to mice in which glutathione was depleted and its synthesis blocked by BSO (1.6 g/kg). Thus reactive oxygen intermediates are likely mediators of LPS-induced HO 1 mRNA accumulation, and glutathione content appears to be one of the factors regulating this accumulation in the liver. Our findings are compatible with the theory that HO-1 induction might have a protective function in vivo when defence mechanisms against oxidants are challenged. PMID- 7998986 TI - Release of Ca2+ from intracellular organelles by peptide analogues: evidence against involvement of metalloendoproteases in Ca2+ sequestration by the endoplasmic reticulum. AB - N-Benzyloxycarbonyl-Gly-Phe-amide (Z-Gly-Phe-NH2), a competitive substrate for metalloendoproteases, mobilizes intracellular Ca2+ and suppresses protein synthesis and processing in a Ca(2+)-dependent, reversible manner. To ascertain whether Z-Gly-Phe-NH2 acts as Ca(2+)-storing organelles, effects of the dipeptide on Ca2+ sequestration by saponin-porated GH3 pituitary cells were examined. Porated preparations sequestered Ca2+ into two compartments with different Ca2+ affinities. Ca2+ accumulation at nM concentrations of free Ca2+ was inhibited by thapsigargin and inositol 1,4,5-triphosphate [Ins(1,4,5)P3], enhanced by oxalate and unaffected by oligomycin. Cation accumulation at microM concentrations of free Ca2+ was sensitive to oligomycin but not to thapsigargin. Z-Gly-Phe-NH2 reduced Ca2+ sequestration by both compartments. The dipeptide mobilized Ca2+ from the high-affinity compartment within 1-2 min without affecting Ca2+ uptake. Ca2+ was mobilized more rapidly by Z-Gly-Phe-NH2 and thapsigargin together than by either agent alone. The presence of a thiol-reducing agent was required for Ca2+ mobilization by Z-Gly-Phe-NH2 but not by thapsigargin or Ins(1,4,5)P3. Ca2+ mobilization by Z-Gly-Phe-NH2 could not be attributed to effects on anion permeability or to actions at Ins(1,4,5)P3 or ryanodine receptors. Results with assorted peptide analogues did not favour suppression of metalloendoprotease activity in the Ca(2+)-mobilizing action of Z-Gly-Phe-NH2. The more hydrophobic analogue Z-L-Tyr-p-nitrophenyl ester was 60-80-fold more potent in mobilizing Ca2+ from intact and porated cells and perturbed the high-affinity Ca(2+) sequestering compartment selectively. Z-Gly-Phe-NH2 and Z-L-Tyr-p-nitrophenyl ester are proposed to release Ca2+ from the endoplasmic reticulum through an ion pore with affinity for hydrophobic molecules containing internal peptide bonds. PMID- 7998988 TI - Characterization of cDNA for murine tripeptidyl-peptidase II reveals alternative splicing. AB - Tripeptidyl-peptidase II (TPP II) is a cytosolic high-M(r) exopeptidase with an active site of the subtilisin type. This paper describes cloning of cDNA encoding murine TPP II. Four clones were isolated from a murine mastocytoma cDNA library and the 5'-end was isolated by use of 5'-RACE (rapid amplification of cDNA ends). A total of 4611 bp were isolated, including the complete coding region. The deduced amino acid sequence shows a 96% overall identity when compared with the previously cloned human TPP II. The remarkably high identity indicates that not only the catalytic domain, but almost the entire subunit, must be of functional importance. Alignment with subtilisin-like serine peptidases identified Asp44, His264 and Ser449 as the catalytic triad, thus defining an extra domain of approximately 200 amino acids between the catalytic Asp and His in TPP II as compared with other subtilases. In addition, it was demonstrated that different polyadenylation signals can be utilized, since two different clones with untranslated 3'-ends of 155 bp and 781 bp respectively have been isolated. Finally, one of the isolated clones contains an extra 39 bp insert encoding 13 amino acids, which implies alternative splicing of the mRNA. PMID- 7998987 TI - L-carnosine (beta-alanyl-L-histidine) and carcinine (beta-alanylhistamine) act as natural antioxidants with hydroxyl-radical-scavenging and lipid-peroxidase activities. AB - Carnosine (beta-alanyl-L-histidine) and carcinine (beta-alanylhistamine) are natural imidazole-containing compounds found in the non-protein fraction of mammalian tissues. Carcinine was synthesized by an original procedure and characterized. Both carnosine and carcinine (10-25 mM) are capable of inhibiting the catalysis of linoleic acid and phosphatidylcholine liposomal peroxidation (LPO) by the O2(-.)-dependent iron-ascorbate and lipid-peroxyl-radical-generating linoleic acid 13-monohydroperoxide (LOOH)-activated haemoglobin systems, as measured by thiobarbituric-acid-reactive substance. Carcinine and carnosine are good scavengers of OH. radicals, as detected by iron-dependent radical damage to the sugar deoxyribose. This suggests that carnosine and carcinine are able to scavenge free radicals or donate hydrogen ions. The iodometric, conjugated diene and t.l.c. assessments of lipid hydroperoxides (13-monohydroperoxide linoleic acid and phosphatidylcholine hydroperoxide) showed their efficient reduction and deactivation by carnosine and carcinine (10-25 mM) in the liberated and bound-to artificial-bilayer states. This suggests that the peroxidase activity exceeded that susceptible to direct reduction with glutathione peroxidase. Imidazole, solutions of beta-alanine, or their mixtures with peptide moieties did not show antioxidant potential. Free L-histidine and especially histamine stimulated iron (II) salt-dependent LPO. Due to the combination of weak metal chelating (abolished by EDTA), OH. and lipid peroxyl radicals scavenging, reducing activities to liberated fatty acid and phospholipid hydroperoxides, carnosine and carcinine appear to be physiological antioxidants able to efficiently protect the lipid phase of biological membranes and aqueous environments. PMID- 7998989 TI - Isolation and characterization of CD47 glycoprotein: a multispanning membrane protein which is the same as integrin-associated protein (IAP) and the ovarian tumour marker OA3. AB - The CD47 glycoprotein was isolated from human erythrocytes by immunoprecipitation using monoclonal antibody (mAb) BRIC-125. Enzymic deglycosylation of the protein showed it contained N-linked oligosaccharides, and trypsin proteolysis of the protein in situ in the erythrocyte membrane cleaved it into two portions, one of which was glycosylated. Both the intact protein and the glycosylated fragment had blocked N-termini. Amino acid sequence was obtained from several proteolytic fragments of CD47. Comparison with the sequence database showed the protein to be very similar to or identical with OA3, a multispanning membrane protein. The protein also appears to be the same as the integrin-associated protein, which has a role in cell adhesion in non-erythroid cells. CD47 has six potential N glycosylation sites, five of which are in an Ig superfamily domain. We show that three of these sites carry N-glycans in erythrocytes. Immunocytochemical staining of human tissues showed that CD47 was broadly distributed on mesenchyme and epithelia at multiple sites. Reactivity was particularly prominent in surface and ductular epithelia, and in the brain. The possible roles of the CD47 glycoprotein are discussed. PMID- 7998990 TI - Vascular smooth-muscle cells contain AT1 angiotensin receptors coupled to phospholipase D activation. AB - We previously showed that angiotensin II (Ang II) and angiotensin-(2-8)-peptide [Ang-(2-8)] activate a phosphoinositide-specific phospholipase C (PLC) and cause calcium mobilization in rat aortic vascular smooth-muscle cells (VSMC), while Ang II and Ang-(1-7) produce prostaglandins. To define further the signal transduction mechanisms activated by angiotensin peptides in smooth-muscle cells, we measured diacylglycerol (DAG) accumulation in response to different angiotensin peptides and its inhibition by subtype-selective receptor antagonists. Both an initial (10 s) and secondary (10 min) phase of DAG production in response to 100 nM Ang II were inhibited by 1 microM losartan (DuP 753), an AT1 antagonist, while 1 microM PD 123177, an AT2 antagonist, was ineffective. In contrast, the heptapeptide Ang-(1-7) did not produce DAG in VSMC. Ang II also caused the hydrolysis of phosphatidylinositol and phosphatidylcholine, the formation of phosphatidic acid and the formation of phosphatidylethanol (PEt) in the presence of ethanol, through activation of a PLD and a PLD-induced transphosphatidylation reaction. A similar concentration of Ang (2-8) also activated PLD; in contrast, Ang-(1-7) was ineffective. PEt production by 100 nM Ang II was significantly attenuated by the AT1 antagonists losartan, its metabolite EXP 3174 or L-158,809 (all at 1 microM), whereas a similar concentration of the AT2 antagonists CGP 42112A or PD 123177 was ineffective. The production of PEt by Ang II was also partially attenuated by the removal of extracellular calcium and potentiated by increasing calcium concentrations, indicating that PLD activity is partially dependent on extracellular calcium. Thus VSMC PLD is coupled to an AT1 receptor and occurs in response to Ang II or Ang-(2-8), but not Ang-(1-7). Since AT1 receptors in VSMC are also coupled to activation of PLC, both PLC and PLD may be coupled to the same or a different AT1 receptor. Alternatively, PLD may be sequentially activated in response to Ang II activation of PLC and a subsequent increase in calcium concentration. PMID- 7998991 TI - Quantification of human serum paraoxonase by enzyme-linked immunoassay: population differences in protein concentrations. AB - Paraoxonase is a serum protein bound to high-density lipoproteins (HDLs). The physiological function of the enzyme is unknown, but a role in lipid metabolism has been postulated. To date, studies of the protein have had to rely on measurements of enzyme activity with various substrates. We have developed a highly specific, competitive e.l.i.s.a. using a previously characterized monoclonal antibody. The assay can detect 20 ng of paraoxonase with a working range of 75-600 ng. Intra- and interassay coefficients of variation were 6.5 and 7.9% respectively. Serum concentrations of paraoxonase in healthy subjects from Geneva and Manchester ranged from 25 to 118 micrograms/ml. There were significant differences in mean concentrations between the two groups (Geneva, 79.3 +/- 18.7 micrograms/ml; Manchester, 59.9 +/- 24.1 micrograms/ml: P < 0.001), differences also apparent when subjects were compared according to paraoxonase phenotype. These appeared to be largely a consequence of differences in apolipoprotein A-I concentrations between the two populations, suggesting that HDL particle number may be important in determining serum levels of paraoxonase. Paraoxonase specific activities were also significantly different between the two groups of subjects (Geneva, 2.08 +/- 0.96 units/mg; Manchester, 3.08 +/- 1.73 units/mg: P < 0.001), which may reflect differences in HDL particle composition. The e.l.i.s.a. should furnish the necessary complement to studies of paraoxonase enzymic activity and has already provided evidence for differences with respect to serum levels of the protein both between populations and between phenotypes within populations. PMID- 7998993 TI - Anti-diabetic biguanides inhibit hormone-induced intracellular Ca2+ concentration oscillations in rat hepatocytes. AB - Rat hepatocytes respond to glycogenolytic stimuli acting via phosphoinositide breakdown (e.g. alpha 1-adrenergic agonists, vasopressin) by oscillations of the free intracellular Ca2+ concentration ([Ca2+]i). We have investigated the action of metformin and phenformin, two anti-diabetic drugs of the biguanide type, on phenylephrine-induced [Ca2+]i oscillations. Metformin and phenformin lowered the frequency of the [Ca2+]i oscillations in a concentration-dependent manner with an IC50 of 0.1 mM and 1 microM, respectively. Simultaneous addition of the biguanides and insulin resulted in a further reduction of the frequency. By contrast, agents which increase the cellular cyclic AMP (cAMP) concentration (glucagon, forskolin, N,2'-O-dibutyryl-cAMP) reversed this inhibition. Furthermore, we investigated whether biguanides influenced the agonist-induced Ca2+ influx across the plasma membrane. When hepatocytes were loaded with the acetoxymethyl ester of fura-2 (fura-2/AM), addition of Mn2+ led to a quench of cellular fura-2, measured at the isosbestic excitation wavelength of 360 nm, until a new steady state was reached. Surprisingly, however, this addition of Mn2+ caused a marked increase of the fluorescence ratio simultaneously measured at 340 and 380 nm during the approach of the 360 nm signal to a new steady state. This observation can be understood on the basis of a compartmentalization of fura 2/AM into intracellular stores sensing the [Ca2+] therein. Subsequent application of phenylephrine resulted in a further decline of the fura-2 signal at 360 nm and a concomitant decrease of the fluorescence ratio. This second phase of the Mn2+ quench and the decrease of the fluorescence ratio could be diminished by addition of either 3 mM metformin or 30 microM phenformin. By contrast, when hepatocytes were loaded with fura-2/pentapotassium salt via a patch pipette, only the initial Mn(2+)-induced quench, measured at 360 nm, but no change of the fluorescence ratio, could be observed. The subsequent addition of phenylephrine and biguanides during the on-going quench caused no further changes, except for a fading oscillatory response. After loading hepatocytes with fluo-3 acetoxymethyl ester, the cells were permeabilized with 5 microM digitonin. Addition of inositol-1,4,5 trisphosphate (IP3) caused a rapid decrease of the remaining cellular fluorescence which could be effectively inhibited by 20 micrograms/ml heparin, indicating a release of Ca2+ from intracellular compartments mediated by IP3. This IP3-induced release of Ca2+ from intracellular stores could be diminished by prior addition of metformin and phenformin.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 7998992 TI - Modulation of phosphoenolpyruvate carboxykinase mRNA levels by the hepatocellular hydration state. AB - Exposure of isolated perfused rat livers to hypo-osmotic (225 mosmol/l) perfusion media for 3 h led to a decrease of about 60% in mRNA levels for phosphoenolpyruvate carboxy-kinase (PEPCK) compared with normo-osmotic (305 mosmol/l) perfusions. Conversely, PEPCK mRNA levels increased about 3-fold during hyperosmotic (385 mosmol/l) perfusions. The anisotonicity effects were not explained by changes in the intracellular cyclic AMP (cAMP) concentration or by changes of the extracellular Na+ or Cl- activity. Similar effects of aniso osmolarity on PEPCK mRNA levels were found in cultured rat hepatoma H4IIE.C3 cells, the experimental system used for further characterization of the effect. Whereas during the first hour of anisotonic exposure no effects on PEPCK mRNA levels were detectable, near-maximal aniso-osmolarity effects were observed within the next 2-3 h. PEPCK mRNA levels increased sigmoidally with the osmolarity of the medium, and the anisotonicity effects were most pronounced upon modulation of osmolarity between 250 and 350 mosmol/l. The aniso-osmolarity effects on PEPCK mRNA were not affected in presence of Go 6850, protein kinase C inhibitor. cAMP increased the PEPCK mRNA levels about 2.3-fold in normo-osmotic media, whereas insulin lowered the PEPCK mRNA levels to about 8%. The effects of cAMP and insulin were also observed during hypo-osmotic and hyperosmotic exposure, respectively, but the anisotonicity effects were not abolished in presence of the hormones. The data suggest that hepatocellular hydration affects hepatic carbohydrate metabolism also over a longer term by modulating PEPCK mRNA levels. This is apparently unrelated to protein kinase C or alterations of cAMP levels. The data strengthen the view that cellular hydration is an important determinant for cell metabolic function by extending its regulatory role in carbohydrate metabolism to the level of mRNA. PMID- 7998994 TI - Characterization of the single Ca(2+)-binding site on the Ca(2+)-ATPase reconstituted with short- or long-chain phosphatidylcholines. AB - On reconstitution of the Ca(2+)-ATPase of skeletal muscle sarcoplasmic reticulum into bilayers of dimyristoleoylphosphatidylcholine [di(C14:1)PC] or dinervonylphosphatidylcholine [di(C24:1)PC] the stoichiometry of Ca2+ binding changes from the usual two Ca2+ ions bound per ATPase molecule to one Ca2+ ion bound per ATPase molecule. For the ATPase in di(C24:1)PC, removal of Ca2+ from the Ca(2+)-bound ATPase results in a decrease in tryptophan fluorescence intensity, as observed for the ATPase in dioleoylphosphatidylcholine [di(C18:1)PC]. For the ATPase in di(C14:1)PC removal of Ca2+ results in no change in tryptophan fluorescence intensity. In the presence of Mg2+, removal of Ca2+ from the ATPase in di(C18:1)PC or di(C24:1)PC results in a decrease in tryptophan fluorescence intensity, but for the ATPase in di(C14:1)PC this results in an increase in intensity. Fluorescence of the ATPase labelled with 4-nitrobenzo-2 oxa-1,3-diazole (NBD) is the same for the ATPase in di(C18:1)PC or di(C24:1)PC, but is markedly greater in di(C14:1)PC, consistent with a 4-fold increase in the E1/E2 equilibrium constant. Addition of Mg2+ to NBD-labelled ATPase in di(C18:1) PC or di(C24:1)PC results in an increase in NBD fluorescence, attributed to stronger binding of Mg2+ to the E1 than to the E2 conformation; addition of Mg2+ had no effect on the fluorescence of the NBD-labelled ATPase in di(C14:1)PC. In the absence of Ca2+, Mg2+ increased the tryptophan fluorescence of the ATPase in di(C14:1)PC, di(C18:3)PC or di(C24:1)PC, with the same binding-constant for Mg2+ in all three lipids. Addition of Mg2+ to the ATPase labelled with 4-(bromomethyl) 6,7-dimethoxycoumarin resulted in a decrease in fluorescence in di(C18:1)PC or di(C24:1)PC but had no effect in di(C14:1)PC. These effects are interpreted in terms of binding of Ca2+ at a single outer Ca2+ binding-site on the ATPase in di(C14:1)PC and di(C24:1)PC, in a conformation in which the inner site is occluded [in di(C14:1)PC] or modified in its affinity for Ca2+ [in di(C24:1)PC]. Thapsigargin binds to the ATPase, reducing its affinity for Ca2+ both in di(C14:1)PC and di(C24:1)PC. PMID- 7998995 TI - Involvement of microsomal vesicles in part of the sensitivity of carnitine palmitoyltransferase I to malonyl-CoA inhibition in mitochondrial fractions of rat liver. AB - Liver mitochondrial fractions as normally isolated contain only 10-20% of total mitochondria and may not be representative of the whole mitochondrial population. This study was designed to evaluate the dependence of the sensitivity of carnitine palmitoyl-transferase I (CPT I) to malonyl-CoA inhibition in mitochondrial fractions that are not normally studied. Four fractions prepared from rat liver were found to be contaminated to different extents by microsome vesicles, on the basis of marker-enzyme activities and micrographic data. Purification of mitochondrial fractions on a Percoll gradient decreased to some extent the microsomal contamination, which was due in part to the existence of close bonds between microsomes and the outer membranes of mitochondria. A greater degree of contamination of mitochondrial fractions by microsomes was correlated with a greater sensitivity of CPT I to malonyl-CoA inhibition. Attempts were made to enhance the sensitivity of CPT I to malonyl-CoA with the use of microsomes. Measurements performed by adding mitochondria and microsomes in the same CPT I assay failed to demonstrate any significant enhancement of malonyl-CoA inhibition. However, addition of ATP to a mixture of mitochondria and microsomes was shown to trigger the binding of both particles, as assessed by enzymic and micrographic data, and to increase the sensitivity of CPT I to malonyl-CoA inhibition. These results demonstrated that the binding of microsomes to mitochondria, unlike the simple mixing of both particles, was capable of altering the sensitivity of CPT I to malonyl-CoA. The data also suggest that this process could be of physiological importance, owing to the frequency of contiguous zones between mitochondria and endoplasmic reticulum observed in sections of intact liver cells. PMID- 7998996 TI - Ca(2+)-mobilizing hormones induce sequentially ordered Ca2+ signals in multicellular systems of rat hepatocytes. AB - The development of hormone-mediated Ca2+ signals was analysed in polarized doublets, triplets and quadruplets of rat hepatocytes by video imaging of fura2 fluorescence. These multicellular models showed dilated bile canaliculi, and gap junctions were observed by using an anti-connexin-32 antibody. They also showed highly organized Ca2+ signals in response to vasopressin or noradrenaline. Surprisingly, the primary rises in intracellular Ca2+ concentration ([Ca2+]i) did not start randomly from any cell of the multiplet. It originated invariably in the same hepatocyte (first-responding cell), and then was propagated in a sequential manner to the nearest connected cells (cell 2, then 3, in triplets; cell 2, 3, then 4 in quadruplets). The sequential activation of the cells appeared to be an intrinsic property of multiplets of rat hepatocytes. (1) In the continued presence of hormones, the same sequential order was observed up to six times, i.e. at each train of oscillations occurring between the cells. (2) The order of [Ca2+]i responses was modified neither by the repeated addition of hormones nor by the hormonal dose. (3) The mechanical disruption of an intermediate cell slowed down the speed of the propagation, suggesting a role of gap junctions in the rapidity of the sequential activation of cells. (4) The same multiplet could have a different first-responding cell for vasopressin or noradrenaline, suggesting a role of the hormonal receptors in the sequentiality of cell responses. It is postulated that a functional heterogeneity of hormonal receptors, and the presence of functional gap junctions, are involved in the existence of sequentially ordered hormone-mediated [Ca2+]i rises in the multiplets of rat hepatocytes. PMID- 7998997 TI - Glycoinositol-phospholipid profiles of four serotypically distinct Old World Leishmania strains. AB - Glycoinositol-phospholipids (GIPLs) are the major glycolipid class and prominant surface antigens of leishmanial parasites. The GIPLs from four serologically distinct Old World strains of Leishmania were characterized to determine inter- and intra-specific differences in these glycolipids. These studies showed that: (1) the major GIPLs of Leishmania topica (LRC-L36) and Leishmania aethiopica (LRC L495) belong to the alpha-mannose-terminating GIPL series (iM2, iM3 and iM4) that are structurally related to the glycosyl-phosphatidylinositol anchors of both the surface proteins and the abundant lipophosphoglycan (LPG). In contrast, the GIPLs from two Leishmania major strains (LRC-L456 and LRC-L580) belong to the alpha galactose-terminating GIPL series (GIPL-1, -2 and -3) that are more structurally related to the LPG anchor; (2) the GIPL profiles of the L. major strains differed in that a significant proportion of the GIPL-2 and -3 species (approximately 40% and 80%, respectively) in LRC-L580 are substituted with a glucose-1-PO4 residue, while this type of substitution was not detected in LRC-L456; and (3) all the GIPLs contained either an alkylacyl- or a lysoalkyl-phosphatidylinositol lipid moiety. However, the alkyl chain compositions of different GIPLs within the same strain was variable. In L. major, the major GIPL species contained alkylacylglycerols with predominantly C18:0 and C24:0 alkyl chains, whereas the glucose-1-PO4-substituted GIPLs contained exclusively lysoalkylglycerols with C24:0 alkyl chains. In L. tropica, the major GIPL, iM2, contained predominantly C24:0 alkyl chains whereas the structurally related iM3 and iM4 GIPLs in this strain contained predominantly C18:0 alkyl chains. In L. aethiopica all the GIPLs (iM2, iM3, iM4) contained C18:0 alkyl chains. These data suggest that the synthesis of the GIPLs may occur in more than one subcellular compartment. The possibility that species-specific differences in the predominantly surface glycan structures may modulate the interaction of the parasite with the insect and mammalian hosts is discussed. PMID- 7998998 TI - Protein kinase C-dependent cyclic AMP formation in airway smooth muscle: the role of type II adenylate cyclase and the blockade of extracellular-signal-regulated kinase-2 (ERK-2) activation. AB - Bradykinin activates adenylate cyclase via a pathway that involves the 'up stream' regulation of phospholipase D (PLD)-catalysed hydrolysis of phosphatidylcholine and activation of protein kinase C (PKC) in airway smooth muscle [Stevens, Pyne, Grady and Pyne (1994) Biochem. J. 297, 233-239]. Coincident signal (Gs alpha and PKC) amplification of the cyclic AMP response can be completely attenuated either by diverting PLD-derived phosphatidate or by inhibiting PKC. In this regard, the coincident signal detector type II adenylate cyclase is expressed as a 110/112 kDa polypeptide in these cells. PKC alpha is not involved in the activation of adenylate cyclase, since a B2-receptor antagonist (NPC567, 10 microM) blocked its bradykinin-stimulated translocation to the membrane and was without effect against both bradykinin-stimulated PLD activity and cyclic AMP formation. Cyclic AMP formation can also be activated by platelet-derived growth factor (PDGF), via a PKC-dependent pathway, although the magnitude of the response is less than that elicited by bradykinin. Nevertheless, these results indicate that multiple receptor types employ PKC to initiate cyclic AMP signals. PDGF (10 ng/ml) elicited the marked sustained activation of extracellular-signal-regulated kinase-2 (ERK-2), whereas bradykinin (1 microM) provoked only modest transient activation of ERK-2. Deoxyadenosine (0.1 mM), a P site inhibitor of adenylate cyclase, blocked bradykinin-stimulated cyclic AMP formation and converted the activation of ERK-2 into a sustained response. Thus the PKC-stimulated cyclic AMP response can limit the activation of ERK-2 in response to bradykinin. These studies indicate that the integration of distinct signal pathways by adenylate cyclase can determine the kinetics of ERK activation, an enzyme that appears to be important for mitogenic progression. PMID- 7998999 TI - Subpopulations of rat hepatocytes separated by Percoll density-gradient centrifugation show characteristics consistent with different acinar locations. AB - Freshly isolated viable rat hepatocytes were separated into five subpopulations on shallow discontinuous Percoll density gradients. The periportal marker enzymes alanine aminotransferase (ALT), malate dehydrogenase (MDH) and lactate dehydrogenase (LDH) showed gradients of increasing activity from the subpopulation of least density (band 1, rho = 1.07 g/ml) to the subpopulation of greatest density (band 5, rho = 1.09 g/ml). The perivenous marker enzymes pyruvate kinase (PK) and glutamate dehydrogenase (GDH) showed gradients of decreasing activity from band-1 cells to band-5 cells. Glutamine synthetase (GS), which is confined to the two or three cell layers around the hepatic venule, was almost entirely restricted to band-1 hepatocytes. Band-5: band-1 ratios of enzyme activity were as follows: ALT, 8.0; LDH, 2.1; MDH, 1.6; GDH, 0.7; PK, 0.2; GS, 0.01. Band-5:band-1 ratios for ALT, LDH, PK and GS were maintained after culture of subpopulations in identical conditions for up to 72 h, whereas the ratios for MDH and GDH decreased and increased respectively towards unity. Band-1 hepatocytes exhibited greater cytotoxicity than band-5 cells after incubation with carbon tetrachloride or paracetamol. These perivenous-selective toxins produced greater decreases in cell viability and greater release of ALT and LDH from band-1 hepatocytes than from band-5 hepatocytes. Conversely, band-5 hepatocytes were more susceptible than band-1 hepatocytes to the cytotoxic effects of 1-naphthylisothiocyanate and methotrexate (known periportal-selective toxins). It is concluded that band-5 hepatocytes are enriched in periportal cells, whereas band-1 hepatocytes are enriched in perivenous cells. Isolation of hepatocyte subpopulations by Percoll density-gradient centrifugation has the considerable advantage that periportal and perivenous cells can be obtained from the same liver. PMID- 7999000 TI - Production of oxidized lipids during modification of low-density lipoprotein by macrophages or copper. AB - The oxidation of low-density lipoprotein (LDL) is implicated in atherosclerosis. Lipids and oxidized lipids were analysed by gas chromatography and gas chromatography-mass spectrometry in human LDL incubated with mouse peritoneal macrophages (MPM) or copper (II) sulphate in Ham's F-10 medium or medium alone (control). MPM-modification and copper-catalysed oxidation of LDL resulted in the formation of oxysterols, mainly cholest-5-en-3 beta,7 beta-diol (7 beta-OH-CHOL); 7%-19% of the initial cholesterol was converted to 7 beta-OH-CHOL in 24 h. 7 beta OH-CHOL levels in control LDL were very low. The increase in 7 beta-OH-CHOL in MPM and copper-oxidized LDL was accompanied by decreases in linoleate and arachidonate and increases in the electrophoretic mobility and degradation of LDL protein by 'target' macrophages. The concerted occurrence of these processes and their similarity in both MPM-modification and copper-catalysed oxidation of LDL were suggested by the highly significant cross-correlations. The fall in polyunsaturated fatty acid (PUFA) was accompanied by a directly proportional increase in electrophoretic mobility of the LDL. Production of 7 beta-OH-CHOL and protein degradation by macrophages showed modest elevations during the initial steep fall in PUFA, and showed their greatest increases as the levels of PUFA slowly approached zero. The levels of 7 beta-OH-CHOL and the degradation of LDL by macrophages were directly proportional. The degradation of LDL by macrophages increased rapidly as the electrophoretic mobility of LDL was slowly approaching its maximum level. PMID- 7999001 TI - Protein kinase C and cyclic AMP-dependent protein kinase phosphorylate phospholemman, an insulin and adrenaline-regulated membrane phosphoprotein, at specific sites in the carboxy terminal domain. AB - Phospholemman, a transmembrane, 72 residue protein enriched in striated muscle and heart [Palmer, Scott and Jones (1991) J. Biol. Chem. 266, 11126-11130], is phosphorylated in response to insulin [Walaas, Horn and Walaas (1991) Biochim. Biophys. Acta 1094, 92-102]. The present study is aimed at identifying the phosphorylation sites of this protein. A synthetic peptide, GTFRSS63IRRLS68TRRR (in the single letter code) and consisting of phospholemman residues 58-72, is a substrate for both protein kinase C and cyclic AMP (cAMP)-dependent protein kinase, with Km values of 6-7 microM for both enzymes. Amino acid sequencing of the phosphopeptide shows that protein kinase C phosphorylates both Ser-63 and Ser 68, while cAMP-dependent protein kinase phosphorylates Ser-68. Thermolytic phosphopeptide mapping of 32P-labelled phospholemman from rat diaphragms shows that treatment with insulin results in labelling of phosphopeptides containing both Ser-63 and Ser-68, whereas treatment with adrenaline results in labelling of the phosphopeptide containing Ser-68. Hence, insulin and adrenaline regulate the phosphorylation of phospholemman, presumably through protein kinase C and cAMP dependent protein kinase, respectively, on partly overlapping phosphorylation sites. PMID- 7999002 TI - Partial purification of a type eta protein kinase C from murine brain: separation from other protein kinase C isoenzymes and characterization. AB - Various murine tissues were tested, by using a protein kinase C-eta-specific antiserum, for the expression of type eta protein kinase C. Brain was found to be the richest source of a type eta isoenzyme. Native protein kinase C-eta was partially purified from the cytosol of murine brain by chromatography on DEAE Sepharose, hydroxyapatite and protamine-agarose. This procedure resulted in a separation of protein kinase C-eta from the other phorbol 12-myristate 13-acetate (PMA)-responsive isoenzymes (alpha, beta, gamma, delta, epsilon) and allowed, for the first time, characterization of the native enzyme. The protein kinase C of type eta from mouse brain is a phospholipid-dependent Ca(2+)-unresponsive protein kinase. Both PMA and bryostatin activate the kinase for phosphorylation of a substrate as well as for autophosphorylation. Various pseudo-substrate-related peptides are suitable as substrates for the eta-type kinase, peptide delta being the best and peptides eta and epsilon the poorest substrates. The enzyme is inhibited by staurosporine and staurosporine-related compounds, such as K252a and Go 6976. However, protein kinase C-eta, like protein kinase C-delta, is around two orders of magnitude less sensitive towards Go 6976 than are the Ca(2+) responsive isoenzymes (alpha, beta, gamma). The eta-type protein kinase C exhibits an extreme tendency to lose its PMA-responsiveness. Consequently, purification of the enzyme to homogeneity has not yet been successful. PMID- 7999004 TI - [3H]PtdIns hydrolysis in postmortem human brain membranes is mediated by the G proteins Gq/11 and phospholipase C-beta. AB - A method utilizing exogenously added [3H]PtdIns incubated with membranes prepared from postmoretem human brain has been shown to provide a means of measuring agonist-induced, guanosine 5'-O-(thiotriphosphate) (GTP[S])-dependent hydrolysis of [3H]PtdIns, thus allowing investigations of the activity of the phosphoinositide second-messenger system in accessible human brain tissue. Agonists inducing [3H]PtdIns hydrolysis include carbachol, trans-1 aminocyclopentyl-1,3-dicarboxylate (ACPD; a glutamatergic metabotropic receptor agonist), serotonin and ATP, with the latter two agonists producing the largest responses. In addition to ATP, [3H]PtdIns hydrolysis was induced by ADP and by 2 methylthio-ATP, indicating that P2-purinergic receptors mediate this process. Subtype-selective antibodies we used to identify Gq/11 and phospholipase C-beta as the G-protein and phospholipase C subtypes that mediated GTP[S]-induced and agonist-induced [3H]PtdIns hydrolysis. These results demonstrate that this method reveals that agonist-induced, GTP[S]-dependent [3H]PtdIns hydrolysis is retained in postmortem human brain membranes with properties similar to rat brain. This method should allow studies of the modulation of phosphoinositide hydrolysis in human brain and investigations of potential alterations in postmortem brain from subjects with neurological and psychiatric diseases. PMID- 7999005 TI - Consensus sequences for ATP-binding sites in protein kinases do not apply to diacylglycerol kinases. PMID- 7999003 TI - Defective regulation of energy metabolism in mdx-mouse skeletal muscles. AB - Our previous finding of a reduced energy metabolism in slow- and fast-twitch skeletal muscle fibres from the murine model of Duchenne muscular dystrophy (the mdx mouse) led us to examine the importance of intracellular glucose availability for a normal energy turnover. To this end, basal and KCl-stimulated (20.9 mM total extracellular K+) rates of glucose uptake (GUP) and heat production were measured in isolated, glucose-incubated (5 mM) soleus and extensor digitorum longus muscles from mdx and control C57B1/10 mice, in the presence and in the absence of insulin (1.7 nM). Under all conditions and for both muscle types, glucose uptake values for mdx and control muscles were similar although heat production was lower in mdx muscles. The marked stimulation of GUP by insulin in both mdx and control muscles had only minor effects on heat production. In contrast, glucose deprivation or inhibition of glycolysis with 2-deoxy-D-glucose (5 mM) significantly decreased heat production in control muscles only, which attenuated, although did not suppress, the difference in basal heat production between mdx and control muscles. Stimulation of heat production by a short-chain fatty acid salt (octanoate, 2 mM) was significantly less marked in mdx than in control muscles. Increased cytoplasmic synthesis of CoA by addition of 5 mM pantothenate (vitamin B5) increased the thermogenic response to glucose more in mdx than in control muscles. We conclude that the low energy turnover in mdx mouse muscle fibres is not due to a decrease of intracellular glucose availability, but rather to a decreased oxidative utilization of glucose and free fatty acids. We suggest that some enzyme complex of the tricarboxylic acid cycle or inefficiency of CoA transport in the mitochondria could be involved. PMID- 7999006 TI - Identification of a new protein family which includes bovine protein kinase C inhibitor-1. PMID- 7999007 TI - Complete cDNA sequence of human lysosome-associated membrane protein-2. AB - The isolation and sequencing of 15 independent human lysosome-associated membrane protein-2 (h-lamp-2) recombinants from a primary human liver cDNA library has resulted in the determination of a transcript sequence significantly longer than previously reported and reveals the utilization of each of the four potential polyadenylation signals (AATAAA) present in the 3' untranslated region. The most 5' extending cDNA clone initiates upstream of the proposed transcription initiation site. A number of differences with published sequences for the h-lamp 2 transcript were observed, some of which result in amino acid changes in the predicted primary structure of the h-lamp-2 protein, and two of which give rise to restriction fragment length polymorphisms. The knowledge of these sequence alterations and polymorphisms is an important consideration for the further analysis of the h-lamp-2 locus with regard to the delineation of function and association with human inherited disorders. PMID- 7999008 TI - Angiotensin II induced expression of transcription factors precedes increase in transforming growth factor-beta 1 mRNA in neonatal cardiac fibroblasts. AB - Angiotensin II (ANG II), a potent vasoconstricting peptide, may act as a growth factor for cardiac muscle cells and induce hypertrophy. We examined the molecular phenotype of neonatal rat cardiac fibroblasts in relation to ANG II by studying the expression pattern of three transcription factors (Egr-1, c-fos and c-jun) and the transforming growth factor-beta 1 (TGF-beta 1). ANG II did not affect cell proliferation and growth of serum deprived neonatal cardiac fibroblasts as predicted from their DNA and protein contents. The expression of Egr-1 and c-fos was induced as early as 15 min that reached maximal levels at 45 min and declined thereafter, whereas c-jun was induced at 45 min and remained elevated up to 2 hrs of ANG II addition. ANG II up-regulated the expression of TGF-beta 1, which became apparent after 1 hr of incubation and reached a plateau between 16-48 hrs. Our results indicate that ANG II transiently stimulates the expression of transcription factors, which may up-regulate TGF-beta 1, that in turn could contribute to the process of myocardial extra-cellular matrix remodeling in hypertrophy. PMID- 7999009 TI - Differential hydrolysis of immobilized phosphatidylcholines by phospholipases A2 and C. AB - A novel phospholipid, 1-fatty acyl-2-(12-aminododecyl) phosphatidylcholine (APC), was synthesized and reacted with two different activated agarose matrices, differing in the spacer arm length: N-hydroxysuccinimidylester agarose (1-atom spacer arm) and N-hydroxysuccinimidylester-6-aminohexanoic acid agarose (8-atom spacer arm). Both immobilized phosphatidylcholines were readily degraded by Bacillus cereus phospholipase C at similar rates. By contrast, Crotalus adamanteus phospholipase A2 hydrolyzed long-spacer arm phosphatidylcholine, but had less than one tenth of the activity towards the short-spacer arm one. These results are interpreted in terms of a chain length-related steric hindrance caused by the matrix, affecting phospholipase A2 but not phospholipase C activity, supporting the view that the first involves a deeper burrowing of the substrate into the enzyme molecule. PMID- 7999010 TI - Interleukin-1 beta induces cytosolic phospholipase A2 gene in rats C6 glioma cell line. AB - Treatment of the rat C6 glioma cell line with interleukin-1 beta (IL-1 beta) resulted in an accumulation of cytosolic phospholipase A2 (cPLA2) in mRNA level. The increase of cPLA2 in mRNA level was observed at 6 hours after treatment of IL 1 beta and reached to the maximal level at 12 hours. The accumulation also remained sustained for up to 72 hours. Dose response curve of IL-1 beta showed that as little as 40 units/ml concentration induced the accumulation of mRNA and 100 units/ml concentration showed the maximal effect. In contrast, cyclooxygenase 2 gene was not affected with treatment of IL-1 beta. PMID- 7999011 TI - Conformational mapping of amyloid peptides from the putative neurotoxic 25-35 region. AB - The secondary structure of amyloid beta A(25-35) and its deletion analogues was studied by circular dichroism (CD), Fourier transform infrared (FTIR) spectroscopy and molecular dynamics calculation. Data of our comparative CD and FTIR measurements in trifluoroethanol suggest that beta A(25-35)NH2 has a preferred beta-sheet conformation. Contrary to this beta A(31-35)NH2 tends to adopt a beta-turn conformation. Based on the comparable neurotoxic effect of beta A(25-35)NH2 and beta A(31-35)NH2 the neurotoxicity likely involves the same 31-35 core sequence and the "biologically active conformation" is a beta-turn rather than a beta-sheet structure. PMID- 7999012 TI - Heterogeneity of protein kinase C activity in human U-373 and G-26 mice glioma cells. AB - Protein kinase C (PKC) enzyme activity in a mouse glioma cell line G-26 and a human glioma cell line U-373 were compared at similar cell confluency in-vitro to establish if a G-26 in-vivo mouse model would be useful to examine the role of PKC inhibitors in controlling human glioma growth in-vivo. Original crude cytosolic and membrane PKC fractions of both mouse glioma G-26 and human glioma U 373 cells did not display significant PKC activity compared to partially purified PKC. Partial purification of mouse glioma G-26 and U-373 cytosolic and membrane fractions showed different cytosolic and membrane PKC activity profiles. Total PKC activity was higher (rho = 0.0001) in human glioma U-373 (7840 picomoles/mg/min) than in mouse glioma G-26 cells (2890 picomoles/mg/min). Thus, results from trials using nude mice human glioma xenografts may be more valid than those obtained from a G-26 in-vivo mouse model for studying the effects of therapeutic drugs on PKC isozymes. PMID- 7999013 TI - Determination of the promoter elements that mediate repression of c-fos gene transcription by thyroid hormone and retinoic acid receptors. AB - Basal and stimulated activity of the c-fos promoter is reduced by triiodothyronine (T3) and retinoic acid (RA) in GH1 cells. We examined the influence of these ligands on the activity of reporter constructs containing the AP-1 site, the serum response element (SRE) and the cyclic AMP responsive element (CRE) of the c-fos promoter under control of an heterologous promoter. T3 and RA decreased the response of AP-1 and SRE sequences to phorbol esters, forskolin or serum but they did not reduce basal or forskolin-stimulated activity mediated by the CRE. Therefore, repression of c-fos gene expression by T3 and RA receptors appears to be exerted through transcriptional interference with the SRE and the AP-1 binding site of the promoter. PMID- 7999014 TI - 8-Hydroxy-2'-deoxyguanosine formation and DNA damage induced by sulfur trioxide anion radicals. AB - The 8-hydroxy-2'-deoxyguanosine (8-OHdG) formation and DNA damage by sulfur trioxide anion radicals (SO3.-) were investigated using ESR spin trapping, HPLC, and electrophoretic assays. Sulfite (SO3(2-) autoxidation generated both hydroxyl (.OH) and SO3.- radicals. Oxidation of SO3(2-) by chromium (VI) generated only SO3.- with much enhanced yield. Incubation of 2'-deoxyguanosine (dG) with SO3(2-) generated 8-OHdG albeit at low yield. Chromium (VI) enhanced the yield four-fold. Electrophoretic assays showed that SO3.- radicals generated by chromium (VI) oxidation of SO3(2-) caused DNA double strand breaks. The results demonstrate that SO3.- radicals are capable of causing dG hydroxylation and DNA double strand breaks. PMID- 7999015 TI - Porcine luteal cells express monocyte chemoattractant protein-2 (MCP-2): analysis by cDNA cloning and northern analysis. AB - From an expression library in lambda UniZAP, derived from porcine corpus luteum (CL), a clone lambda MCP9 was detected by hybridization with a porcine MCP-1 specific probe. A pBluescriptSK-derivative pMCP9 was generated from lambda MCP9 by in vivo excision and was shown to contain an open reading frame (ORF) encoding a protein highly homologous to bovine monocyte chemoattractant protein-2 (MCP-2). Comparison of amino acid sequences of known MCPs identified the protein encoded by pMCP9 as porcine MPC-2. The 3' untranslated region of pMCP9 was completed by 3' RACE. Northern analysis using RNA from porcine luteal cells and probes specific for porcine MCP-1 and MCP-2 revealed that porcine luteal cells express both MCPs. According to Southern analysis MCP-2, like MCP-1, is specified by a single copy gene. PMID- 7999016 TI - Nanosecond absorption study of kinetics associated with carbon monoxide rebinding to hemoglobin S and hemoglobin C following ligand photolysis. AB - The absorption spectra of photolysis intermediates of the CO complex of hemoglobin S and hemoglobin C, in the tetramer form, have been measured between 10 ns and 200 ms after excitation. These data were analyzed using singular value decomposition (SVD) and global analysis to determine kinetic lifetimes associated with various processes involved in CO recombination. The results of this analysis show that, in the tetramer (non-aggregated) form, hemoglobin S and hemoglobin C exhibit the same kinetics associated with CO recombination as hemoglobin A. PMID- 7999017 TI - Vanadate oligoanions interact with the proton ejection by the Ca2+ pump of sarcoplasmic reticulum. AB - Decameric vanadate differs from other oligomeric vanadate species in inhibiting Ca2+ uptake and H+ ejection promoted by sarcoplasmic reticulum ATPase. A decavanadate solution, 2 mM in total vanadium, containing about 200 microM decameric species, inhibits by about 50% the uptake of Ca2+ and by 75% the H+ ejection, whereas 2 mM nominal monovanadate slightly increases the uptake of Ca2+ and inhibits the ejection of H+ by 25%. Moreover, decavanadate linearly increases the Ca2+/H+ ratio, whereas monovanadate mimicks decavanadate behavior only at concentrations up to 1.2 mM. For higher concentrations of monovanadate, this effect is reversed probably due to the formation of metavanadates, namely tetravandate. It is concluded that Ca2+ uptake is tightly coupled to proton ejection through molecular events that are sensitive to the interaction of vanadate species. Apparently, the stoichiometry is variable and modulated by molecular events involved in vanadate interaction suggesting alterations in the energetic coupling associated with Ca2+ translocation. PMID- 7999019 TI - Role of bound GDP in the stability of the rho A-rho GDI complex purified from neutrophil cytosol. AB - The rho A-rho GDI complex purified from bovine neutrophil cytosol was found to contain GDP as the only bound nucleotide at a ratio of 1 mol of GDP per mol of complex. The rho GDI component of the complex (pI 4.8-5.0, apparent molecular mass 28-29 kDa) and the rho A component (pI scattered between 5.0-6.2, apparent molecular mass 24 kDa) were resolved by 2D gel electrophoresis. Upon dephosphorylation of bound GDP by apyrase, the rho A component of the complex was prone to proteolytic cleavage. The integrity of rho A in the presence of apyrase was preserved by addition of excess GTP. These data suggest that rho A liganded by GDP in the rho A-rho GDI complex is maintained in a conformation that escapes action of proteases. PMID- 7999018 TI - Novel antagonist of endothelin ETB1 and ETB2 receptors, BQ-788: effects on blood vessel and small intestine. AB - The effects of a peptide, BQ-788 [N-cis-2, 6-dimethyl-piperidinocarbonyl-L-gamma methylleucyl-D-1- methoxycarbonyltryptophanyl-D-norleucine], on isolated blood vessel and small intestine were examined. In the rat aorta, BQ-788 antagonized the endothelium-dependent, ETB1 receptor-mediated relaxation due to endothelin (ET)-3 with EC50 of 3 microM. In the rat aorta without endothelium, 10 microM BQ 788 weakly antagonized the ETA1-mediated contractile effects of ET-1 and ET-3. In the rabbit saphenous vein, it has been shown that ETA1, ETA2, ETB1 and ETB2 receptors mediate contraction. BQ-788 (10 microM) almost completely inhibited the contractile effect of sarafotoxin S6c (an ETB1 and ETB2 agonist). BQ-788 also antagonized the contractile effect of ET-3 (an ETA1, ETB1 and ETB2 agonist) more strongly than desensitization of ETB1 and ETB2 receptors. However, BQ-788 did not antagonize the effect of ET-1 (agonist of all four receptors). In the guinea pig ileum, 10 microM BQ-788 completely inhibited the relaxation mediated by ETB1 and ETB2 receptors. These results suggest that BQ-788 is a novel antagonist of ETB1 and ETB2 receptors with weak antagonistic effect on the ETA1 receptor. PMID- 7999021 TI - Impairment of respiratory functions in mitochondria of rats with an inherited hyperproduction of free radicals. AB - The functional characteristics of liver mitochondria and physical-chemical properties of mitochondrial membranes were studied in S rats with congenitally enhanced capacity to free radical generation in comparison to those in Wistar rats. It was shown previously that intense lipid peroxidation, numerous DNA rearrangements, protein oxidation, morbid states resembling human degenerative diseases and short life-span are characteristic of S rats. In present study we have demonstrated that in S rats at the age of 2-3 months the respiratory rate of the mitochondria in active metabolic state is lower than in Wistar rats, and so are the values for the respiratory control ratio, oxidative phosphorylation and membrane potential. By 10-12 months of age the decrease of the respiration rate and oxidative phosphorylation in S rat mitochondria become even more dramatic. These changes are associated with a decrease in the extent of dip of proteins into the membrane lipid layer or with the increase in the amount of protein aggregates. The results add to the understanding of the nature of morbid conditions developed under the effect of intensive free radical generation and to the comprehension of their role in aging. PMID- 7999020 TI - On the mechanism of cytosolic phospholipase A2 activation in CHO cells carrying somatostatin receptor: wortmannin-sensitive pathway to activate mitogen-activated protein kinase. AB - We examined the mechanism of arachidonate release induced by somatostatin-14 (SS14) in CHO-K1 cells overexpressing rat hippocampal somatostatin receptor SSTR4. SSTR4 couples to pertussis toxin (PTX)-sensitive G-protein in CHO cells and does not lead to phosphoinositides breakdown or intracellular calcium ([Ca2+]i) mobilization (Bito et al.: J. Biol. Chem. 269, 12722-12730, 1994). SSTR4 activated mitogen-activated protein (MAP) kinase and induced the phosphorylation of 85kDa cytosolic phospholipase A2 (cPLA2), in a PTX-sensitive manner. Furthermore, activations of both MAP kinase and cPLA2 were inhibited by treatment with wortmannin, at almost identical IC50 values. Thus, SSTR4 appears to stimulate MAP kinase and cPLA2 in a Gi-dependent, and through a wortmannin sensitive pathway. We also showed that stimulation with SS14, in combination with calcium-ionophore, strongly enhanced arachidonate release from these cells. PMID- 7999022 TI - Effect of alcohol on expression of heat shock protein 73 in monolayers of hepatocytes from alcohol-exposed rats. AB - Alcohol dramatically reduced loss of heat shock proteins (HSP73) and prevented morphological damage in monolayers of hepatocytes prepared from alcohol-fed rats. The monolayers were treated with 0, 5, 25, or 100 mM alcohol and triplicate samples were assayed at 24, 48, 72, and 96 hr after exposure. The content of HSP73 was measured by PAGE electrophoresis and Western blotting with a mouse monoclonal anti-HSP70 IgG antibody. HSP72 is not expressed under these conditions. Damage to the hepatocytes, quantified by leakage of lactate dehydrogenase (LDH), was also decreased by 100 mM alcohol. Although the initial 100 mM alcohol concentration decreased logarithmically to 1.7 mM over the first 24 hr, the effect of alcohol on HSP73 loss, LDH leakage, and morphological damage was most pronounced at 96 hr. PMID- 7999023 TI - Identification of actin isoforms after in situ hydroxylamine cleavage on sequencer membranes: serum actin is a cytoplasmic isoform. AB - Actin was isolated from fetal bovine serum by means of affinity chromatography on DNase I-Sepharose, reversed phase chromatography and SDS-gel electrophoresis. It was identified as a cytoplasmic isoform by direct micro sequence analysis of hydroxylamine cleavage products which had been generated in situ after covalent linkage of the protein to sequencer membrane disks through arylamine or isothiocyanato functionalities. PMID- 7999024 TI - Potential use of IgG2-ELISA in the diagnosis of chronic elephantiasis and IgG4 ELISA in the follow-up of microfilaraemic patients infected with Brugia malayi. AB - Sera from fifty subjects with different presentations of Brugian filariasis and from common soil-transmitted helminth infections were tested for specific anti filarial IgG and its subclasses. Anti-filarial IgG, IgG1 and IgG3 showed cross reactivities with soil-transmitted helminthic infections and no significant differences in optical densities among the various groups of filarial patients. In comparison with other groups of subjects, IgG4-ELISA of sera from microfilaraemic patients and some previously microfilaraemic patients showed a significant increase in optical density readings, while IgG2-ELISA showed elevated optical density readings in sera of patients with chronic elephantiasis. Therefore IgG2-ELISA is potentially useful in the diagnosis of brugian chronic elephantiasis while IgG4-ELISA may be beneficial for follow-up diagnosis of treated microfilaraemic patients. PMID- 7999026 TI - Selective cytotoxicity of transformed cells but not normal cells by a sialoglycopeptide growth regulator in the presence of tumor necrosis factor. AB - The tumor necrosis factor-alpha (TNF)-resistant, SV40-transformed, murine fibroblast cell lines, F5b and F5m, became sensitive to TNF-mediated cytolysis after treatment with a biologically active 18 kDa peptide fragment (SGP) derived from a 66-kDa parental cell surface sialoglycoprotein. Neither TNF nor the SGP alone exhibited cytotoxicity to the two SV40-transformed cell lines. However, Balb/c 3T3 cells, incubated with SGP alone or with SGP and TNF, were not killed. Therefore, SGP can selectively sensitize cells for TNF alpha-mediated cytotoxicity. This selective sensitization may be due to the previously documented ability of the SGP to selectively mediate cell cycle arrest. PMID- 7999025 TI - Protein kinase C isozyme pattern in liver hyperplasia. AB - Lead nitrate, a potent activator of protein kinase C, is able to induce reversible rat liver hyperplasia. This phenomenon shows sex-related growth differences: liver hyperplasia as well as its regression by apoptosis occurred earlier and was more pronounced in male than in female rats. Dietary choline administration to females causes a shift of growth pattern towards the male values. Analysis of protein kinase C isoenzymes with hydroxylapatite column chromatography at time points crucial for lead-induced liver proliferation in male, female and choline-treated female rats showed a significant down-regulation of beta and alpha PKC activities and a marked activation of epsilon PKC. The fluctuation of these activities could be related to the rates of DNA synthesis. These data suggest that the observed PKC isoenzymes could be involved in the signal transduction pathway leading to lead-induced liver proliferation. PMID- 7999027 TI - Processing of human prosomatostatin in AtT-20 cells: S-28 and S-14 are generated in different secretory pathways. AB - Somatostatin-14 (S-14) and somatostatin-28 (S-28) are generated by differential processing of a single precursor at a dibasic (R-K) or monobasic (R) proteolytic cleavage site, respectively. To study the pathways of processing of prosomatostatin, we have expressed in AtT20 cells cDNA encoding human prosomatostatin and prosomatostatin mutated in one or the other processing site. Analysis of the peptides present in cell extracts or culture media before and after stimulation of the cells with 8-BrcAMP indicated that prosomatostatin can enter three distinct secretory pathways where it is differently processed: 1) prosomatostatin was secreted through the constitutive pathway; 2) the regulated secretory pathway generated S-14 which was released upon stimulation of the cells with 8-BrcAMP; 3) an alternative pathway, insensitive to 8-BrcAMP produced S-28 and S-14. Moreover, our results suggest that the R-K processing site used to produce S-14 is an important structural feature for targeting the precursor to the regulated secretory pathway. PMID- 7999028 TI - The thyroid hormone inhibits the thyrotropin receptor promoter activity: evidence for a short loop regulation. AB - Thyrotropin, by binding its specific receptor on the plasma membrane of the thyrocyte, regulates thyroid function and differentiation. In FRTL5 cells, thyrotropin down-regulates the thyrotropin receptor (TSHr) promoter activity and induces the transcription of the alpha form of thyroid hormone receptor (TR-alpha 1). In this study we show that the thyrotropin receptor down-regulation, induced by thyrotropin, is mediated by TR-alpha 1. The thyroid hormone receptor binds, in vitro, the thyrotropin receptor minimal promoter and inhibits promoter activity in cotransfections experiments in CV 1 cells. The inhibition is achieved only in the presence of the thyroid hormone. The TSHr promoter mutated in the thyroid hormone receptor binding site does not bind TR, in vitro, and its activity is not inhibited, in cotransfection experiments, in CV 1 cells. The same mutation abolishes the TSH mediated down-regulation of the TSHr promoter activity in FRTL5 thyroid cells. These results support the hypothesis of a regulatory short loop of thyroid hormone in thyroid cells. PMID- 7999029 TI - Evidence for the glycosylation of the granulocyte colony-stimulating factor receptor. AB - The granulocyte colony-stimulating factor receptor (G-CSFR) was overexpressed in WEHI-3B D+ myelomonocytic leukemia cells by the transfection of an expression plasmid containing the murine G-CSFR cDNA. Two different forms of the G-CSFR were observed in these cells by western blotting. Metabolic labeling and cell surface labeling demonstrated that the majority of the G-CSFR exists in a non-mature form and is presumably present in the cytoplasm as a 115-kDa protein. A relatively small portion of the G-CSFR is present as the fully mature form on the cell surface as a 150-kDa protein; this form of the G-CSFR binds to granulocyte colony stimulating factor (G-CSF). Both the mature and non-mature forms of the G-CSFR appear to be N-glycosylated, as determined by glycanase digestion and inhibition of glycosylation by tunicamycin. Glycosylation of the G-CSFR may be of importance for the transport of the receptor to the cell surface. PMID- 7999030 TI - Biosynthesis of isoprenoid compounds in cattle filarial parasite Setaria digitata. AB - The biological significance of isoprenoid compounds such as ubiquinones, prenols and sterols have been well established. The presence and biological function of the two quinones Q6 and Q8 in the cattle filarial parasite Setaria digitata have already been reported. Inhibition of the function of quinone was already shown to be an effective means of controlling the filarial parasite. Detailed investigations of the non-saponifiable lipids from S. digitata using column, thin layer, reverse phase and high performance liquid chromatography showed the presence and formation of isoprenoid compounds such as prenols and sterols, in addition to the two quinones. Blocking of the biosynthesis of these useful compounds may prove to be an additional means of control of filarial parasites. PMID- 7999031 TI - Neomycin inhibition of hormone-stimulated smooth muscle contractions in myometrial tissue. AB - These studies sought to determine the effects of neomycin, a phospholipase C inhibitor, on hormone-stimulated myometrial contractions. For these studies, computer digitalized in vitro isometric contraction data were analyzed for changes in contractile activity in response to oxytocin and aluminum fluoride with and without neomycin. Neomycin (1-5 mM) produced dose-related inhibition of oxytocin and aluminum fluoride-stimulated myometrial contractions. This neomycin effect was apparent within 2-3 minutes of addition and was completely reversible, with resolution of its inhibitory effects within 6-8 minutes of washout. This study is the first to demonstrate the functional effect of neomycin inhibition of the phosphatidylinositol signaling pathway in myometrial smooth muscle tissue. PMID- 7999032 TI - Adrenomedullin, a newly discovered hypotensive peptide, is a potent bronchodilator. AB - The present study was designed to examine the effect of adrenomedullin (AM), a novel vasorelaxant peptide originally isolated from human pheochromocytoma, on histamine- or acetylcholine-induced bronchoconstriction in anesthetized guinea pigs in vivo. AM significantly inhibited acetylcholine-induced bronchoconstriction in a dose-dependent fashion. AM also significantly inhibited histamine-induced bronchoconstriction, but 10(-10) M AM had no significant inhibitory effect on this response. We also found that AM induced a long-lasting bronchodilator response, while isoproterenol induced transient bronchodilation. These preliminary findings suggest that AM may play important roles in airway function. PMID- 7999033 TI - Complement activation in rats by liposomes and liposome-encapsulated hemoglobin: evidence for anti-lipid antibodies and alternative pathway activation. AB - Intravenous injection of hemoglobin-containing liposomes (LEH) caused a significant reduction in plasma hemolytic complement activity in rats on a time scale of minutes. Liposomes without hemoglobin also caused complement consumption, but less than LEH, while free hemoglobin was without effect. Consistent with complement activation, the LEH-induced drop in plasma hemolytic complement activity was closely paralleled by an increase in plasma thromboxane B2 level. Studies to determine the mechanism of complement activation demonstrated the presence of natural antibodies in rat serum against all lipid components of LEH, thus, the potential for classical pathway activation. Yet, in vitro incubation of LEH with rat serum showed that: 1) EGTA/Mg++, which inhibits complement activation through the classical pathway, did not inhibit complement consumption by LEH, and 2) the use of serum preheated at 50 degrees C, which inhibits C activation through the alternative pathway by selectively depleting factor B, effectively reversed the complement-consuming effect of LEH. Consequently, LEH-induced complement activation in rat serum seems to involve primarily the alternative pathway. PMID- 7999034 TI - Aminoethylcysteine ketimine decarboxylated dimer protects submitochondrial particles from lipid peroxidation at a concentration not inhibitory of electron transport. AB - In contrast with other inhibitors of the NADH dehydrogenase of the respiratory chain, the decarboxylated dimer of aminoethylcysteine ketimine protects bovine heart submitochondrial particles (SMP) from the NADH-Fe(+3)-ADP-induced lipid peroxidation. This effect, measured as inhibition of malondialdehyde formation, is concentration-dependent in the range 0.02-0.2 mM. This range of concentration is not inhibitory on NADH-oxidase activity of SMP. Furthermore the dimer is able to counteract the malondialdehyde formation stimulated by the Complex I inhibitors rotenone and N-methyl-4-phenylpyridinium (MPP+). PMID- 7999035 TI - Glycosylated nature of testosterone 5 alpha-reductase 2 purified from human prostate. AB - 5 alpha-reductase 2 from human prostate solubilized into an active and stable form using a non-ionic detergent octyl glucoside was successfully purified using a four-step chromatographic procedure. The enzyme was obtained as an apparently homogeneous protein exhibiting an apparent molecular weight of 42 kDa upon SDS PAGE. Con A, DBA, UEA-I, and RCA60 lectins recognized this protein. After treatment with O-glycosidase and neuraminidase, a protein of an apparent molecular weight about 30 kDa appeared. On the other hand, N-glycosidase treatment of this enzyme had no effect. These results indicate that the human prostate testosterone 5 alpha-reductase 2 is an O-glycosylated sialoglycoprotein with a peptide moiety of about 30 kDa; the oligosaccharide side chains contain mannose, N-acetyl galactosamine, fucose, galactose and sialic acids. PMID- 7999036 TI - Stereospecificity of hydride transfer and substrate specificity for FMN containing NAD(P)H-flavin oxidoreductase from the luminescent bacterium, Vibrio fischeri ATCC 7744. AB - The stereospecificity of the hydride transfer in NAD(P)H-flavin reductase reaction of V. fischeri ATCC 7744 was determined by 1H-NMR spectroscopy using stereospecifically labeled reduced beta-nicotinamide adenine dinucleotide (beta NADH). The recombinant flavoenzyme, purified from E. coli cells, selectively transferred the pro-R hydrogen at the C-4 position of the nicotinamide ring to flavin and is therefore classified as an A-side specific enzyme. Lumiflavin was used for the reductase reaction, but lumichrome and alpha-NADH were not utilized as electron acceptor and donor, respectively. PMID- 7999037 TI - Isolation and functional expression of human pancreatic peptidylglycine alpha amidating monooxygenase. AB - Pancreastatin (PST) is processed from chromogranin A and the C-terminal amide of the peptide is an absolute requirement for biological activities. Human pancreatic carcinoma cells QGP-1 which produce both chromogranin A and PST were used to isolate cDNAs encoding two forms of peptidylglycine alpha-amidating monooxygenase (PAM). The two forms are a full length bifunctional enzyme and a variant lacking the transmembrane domain-coding region. When the cDNAs of these two forms were expressed in COS-7 cells, cells transfected with the predicted soluble form released into the culture medium a very much higher amidating activity which converts human chromogranin A-(273-302) to PST-29. The optimal pH for amidating activity was 5.4 and Cu2+, ascorbate and catalase were required as cofactors for the both forms of PAM. Km values for the membrane-bound and the soluble forms of PAM were 15.7 +/- 3.1 microM and 12.4 +/- 1.6 microM, respectively. These results demonstrate that both forms of PAM can function in the posttranslational processing of chromogranin A to PST in the environment of a secretory vesicle. PMID- 7999038 TI - Changes in 1,4,5-inositol trisphosphate binding following partial hepatectomy. AB - Hepatic parenchymal cells possess two receptors for 1,4,5-trisphosphate, one isolated with the plasma membrane fraction and another isolated with the nuclear fraction. Their interaction with antibodies generated against the receptor in the cerebellum indicates that these two receptor proteins are different. The potential involvement of the nuclear receptor in rapid cell proliferation was tested by measuring [3H]-IP3 binding, following partial hepatectomy. In nuclear fractions isolated 18 hours after the operation, a 33% decline in binding sites was detected. In nuclear fractions isolated 30 hours after the operation, a 60% decline in the binding sites was detected, but the Kd remained unchanged. A 70% decrease in binding sites was also detected in the plasma membrane fraction. These results show that partial hepatectomy is associated with a parallel loss of receptor sites in the nuclear and plasma membrane fractions. PMID- 7999039 TI - Aromatic nitroreductase from the basidiomycete Phanerochaete chrysosporium. AB - A membrane-associated aromatic nitroreductase activity was identified in cell free extracts of the lignin-degrading fungus Phanerochaete chrysosporium. The enzyme catalyzed the nitro group reduction of 1,3-dinitrobenzene, 2,4 dinitrotoluene, 2,4,6-trinitrotoluene, 1-chloro-2,4-dinitrobenzene, and 2,4 dichloro-1-nitrobenzene. The corresponding hydroxylamines and/or amines were identified as reaction products by HPLC and/or GC-MS. 1-Nitroso-3-nitrobenzene and 1-hydroxylamino-3-nitrobenzene also were reduced by the enzyme, suggesting they were intermediates in the reaction. The enzyme required NAD(P)H as a cosubstrate and the optimal pH and temperature for the reaction were 6.5 and 50 degrees C, respectively. Enzyme activity was not observed in the presence of molecular oxygen. The membrane-associated enzyme could be solubilized with the nonionic detergent Triton X-100. PMID- 7999040 TI - Involvement of superoxide radical in signal transduction regulating stomatal movements. AB - Stomatal movements are regulated by alternate phase transition in the lipophilic domains of membrane initiated by blue light through activation of plasmalemma redox system. ABA blocks the blue light activated redox reactions leading to the accumulation of superoxide (O2.-) radical inducing melting of the membrane and increased fluidity. Phenolic compounds which reverse the ABA effects reduce O2.- radical and thereby reverse phase transition in lipophilic domains of membrane. Stomatal movements thus appear to be regulated by blue light activated redox reactions involving formation of O2.- radical and its reduction by the reducing equivalents available in the GCPs. PMID- 7999041 TI - Stabilization of tetrahelical DNA by the quadruplex DNA binding protein QUAD. AB - The 57-kDa hepatic nuclear protein QUAD binds tightly and specifically a parallel tetrahelical form of the IgG switch region DNA (Weisman-Shomer, P. and Fry, M. (1993) J. Biol Chem. 268, 3306-3312). Here we show that QUAD is a heat-stable protein, maintaining approximately 90% of its tetrahelix binding activity after 10 min at 100 degrees C and becoming fully inactivated only after 30 min at 100 degrees C. To demonstrate that QUAD protects bound quadruplex DNA, naked and QUAD bound tetrahelices were boiled, the protein residue in the complex was digested with trypsin and quadruplex and single-strand forms of the DNA component were resolved by electrophoresis. Whereas naked quadruplex DNA became fully denatured after 2 min at 100 degrees C, 55% of the QUAD-bound DNA was conserved as a tetrahelix after 6 min at 100 degrees C. These findings support the proposal that QUAD may act in vivo to stabilize tetrahelical DNA. PMID- 7999042 TI - Amino acids in the amino terminal region of the rat prolactin contribute to PRL receptor binding and NB2 cell proliferation activity. AB - To elucidate the structure-function relationship of rat prolactin, seven conserved or semi-conserved amino acids in the amino terminal region were investigated by site-directed mutagenesis. The antigenicity and electrophoretic mobility, as well as receptor binding and Nb2 cell proliferation in various mutants were assayed. Mutants with the cysteine at position 9 replaced with glycine (C9G), as well as R19G, S24A, Y26S, Y42F and Y42S, decreased the activities of receptor binding and Nb2 cell proliferation. A mutation of residue at 42 resulted in a loss of most of the activities. A mutation of residue at 39 (D39V and D39G) increased both receptor binding and cell proliferation activities. Thus, this study demonstrated that the seven amino acids in the amino terminal region contribute to the biological function of rat prolactin and that tyrosine at 42 is especially important. PMID- 7999043 TI - Production of two phosphoproteins from the NS5A region of the hepatitis C viral genome. AB - Hepatitis C virus produces about 12 viral proteins by proteolytic cleavage of the viral polyprotein precursor produced from the largest open reading frame in the viral genome. We have analyzed the production of viral nonstructural proteins with an in vivo transient expression system using COS-1 cells. Two proteins, a 56 kDa protein and a 58-kDa protein, were produced from the nonstructural region 5A (NS5A), which has the potential to produce a 49 kDa protein. We showed that these proteins are phosphorylated at the serine residues. The presence of the two proteins was reflected by different degrees of phosphorylation. Moreover, the hyper-phosphorylation of p58 was shown to depend on the presence of NS4A, another hepatitis C virus protein. PMID- 7999044 TI - Apoptosis in brain and gut tissue of mice fed a seed preparation of the cycad Lepidozamia peroffskyana. AB - Apoptosis (programmed cell death) was identified in histological sections of brain and gut tissue of adult mice fed seed preparations from the cycad Lepidozamia peroffskyana. This form of cell death was also found at high levels in brain tissue from neonatal mice born from a cycad-fed mother. The discovery was made during re-appraisal of archival tissue from a study of toxic properties of L. peroffskyana. Ingestion of appropriately prepared food or medicine derived from another cycad, Cycas circinalis, is thought to be associated with several motor neurone and other neurodegenerative disorders of some Pacific island inhabitants. Apoptosis is cell death under gene control. From the present study, presence of apoptosis in brain tissue after cycad toxicity may provide a link between cycad ingestion and development of neurodegenerative disorders and may provide a novel explanation for localization of some neurodegenerative disorders, as some inhabitants may have a genetic susceptibility to apoptosis induced by cycad toxicity. PMID- 7999045 TI - Expression of the Xist gene in urogenital ridges of midgestation male embryos. AB - We show by RT-PCR analysis that transcripts from the Xist gene, which is normally expressed from the inactive X chromosome of female somatic cells and postnatal male germ cells, are transiently expressed also in male embryos around the time of testis differentiation, mainly in somatic cells of urogenital ridges. In the postnatal testis, we find that Xist transcripts are mainly localized within the nucleus of haploid spermatids. These findings suggest that inactivation of the X chromosome might occur not only in adult male germ cells, but also, transiently, in somatic cells of the male urogenital ridge. Both in the embryonal gonad and in differentiating germ cells Xist expression in males overlaps the pattern of expression of the testis determining gene Sry. PMID- 7999046 TI - Specific inhibition of rat pancreatic insulin or glucagon release by receptor selective somatostatin analogs. AB - A group of new peptide ligands displaying high selectivity for binding to somatostatin receptor subtypes 2, 3 or 5 have been used to characterize somatostatin receptor involvement in the inhibition of glucagon secretion in rats. It was found that NC-8-12 and DC-25-100, which have high affinity for SSTR2 and much less affinity for the type 5 receptor, were by far the most potent inhibitors of glucagon secretion with EC50s of 48 and 18 nmole, respectively, relative to somatostatin itself (EC50 131 nmole). These two analogs were actually much less potent than somatostatin in inhibiting glucose-stimulated insulin release. In contrast, DC-23-99 (a type 5 receptor selective analog), which was previously found to be a more potent inhibitor of insulin secretion than somatostatin, had considerably less potent (EC50 410 nmole) effects on glucagon release. The SSTR3-specific ligands, DC-25-12 and DC-25-20, were not effective at the doses tested. The differing spectra of activities of these analogs suggest that inhibition of insulin and glucagon secretion in rats is mediated by entirely different somatostatin receptor populations. PMID- 7999047 TI - Regulation of rat glucagon receptor expression. AB - This report describes the isolation of a cDNA for the rat glucagon receptor by using the glucagon-like peptide 1 receptor cDNA as a probe. Northern blot analysis using the cDNA clone showed that the message encoding the receptor is approximately 2.3 kb in size and is expressed only in liver and kidney among seven tissues tested. To study how glucagon receptor expression is regulated in vivo, the levels of hepatic glucagon receptor mRNA were measured in diabetic mouse model, db/db and control (db/+) mice. Interestingly, the receptor mRNA levels were similar between diabetic and control mice. In contrast, the number of hepatic glucagon receptors in diabetic mice measured by binding assays was significantly higher than that found in normal mice. These results suggest that the major regulation in hepatic glucagon receptor expression in vivo is at the posttranscriptional level. PMID- 7999048 TI - Characterization of the 30-kDa enzyme from red blood cells that cleaves ubiquitin protein conjugates. AB - A 30-kDa enzyme from red blood cells responsible for the recycling of free Ubiquitin has been characterized. This enzyme was previously known to have a Ubiquitin-C-terminal hydrolase activity on adducts of Ubiquitin to small compounds. In this study it was shown that the 30-kDa enzyme contained Ubiquitin C-terminal hydrolase activity toward biosynthetic precursors of Ub as well as isopeptidase activity toward Ubiquitin histone conjugates. Detailed inhibition experiments with Ubiquitin aldehyde, iodoacetamide, and heat inactivation showed that the enzyme isopeptidase activity was affected differently from its hydrolase activity. PMID- 7999050 TI - PCR-cloning of goldfish and tilapia metallothionein complementary DNAs. AB - Metallothionein (MT) is believed to be a sensitive and effective "biomarker" for monitoring metal contamination in fish. Comparison of amino acid sequences between flounder MT and trout MT revealed that there is a conserved region at their N-terminals. Using oligonucleotides derived from this conserved region, reverse transcription- polymerase chain reaction (RT-PCR) was performed to obtain MT complementary DNAs (cDNAs) from goldfish, Carassius auratus, and tilapia, Tilapia mossambica. These cDNA probes would be useful in developing sensitive PCR based methods to detect MT gene expression for monitoring metal pollution in local waters. PMID- 7999049 TI - Western blot analysis of thyrotropin receptor expression in human thyroid tumours and correlation with TSH-binding. AB - Expression of thyrotropin receptor (TSHr) was analyzed in normal human thyroids and differentiated thyroid tumours by Northern blotting of total RNA and by Western blotting of detergent-solubilized membrane proteins with an antibody specific for the extracellular domain of TSHr. Under nonreducing conditions TSHr stained as a 90-kDa protein in normal thyroid tissue. Expression varied in differentiated carcinomas from normal to not detectable in parallel to steady state TSHr mRNA levels and TSH binding in a TSH binding assay. The negative expression of TSHr in some patients with differentiated carcinomas may have consequences for the TSH suppressive treatments of these patients. PMID- 7999051 TI - Multiple deletions of the mitochondrial DNA in polymyalgia rheumatica. AB - We analyzed the mitochondrial DNA of patients with polymyalgia rheumatica, a disease frequently associated with mitochondrial myopathy. In an attempt to study the deletions, we have developed a qualitative PCR method using a highly thermostable polymerase in order to amplify multiple mitochondrial DNA large fragments (up to 12 kb). PCR serves to observe both deleted and normal fractions of the mitochondrial DNA. We found multiple deletions of the mitochondrial DNA in all of the patient muscles. Although these muscles harbored many ragged red fibers, we found no point mutations of the tRNA(Leu)(UUR)) and the mutation at nucleotide position 8344 was not present. PMID- 7999052 TI - Distribution of lysosomal protective protein in human tissues. AB - We raised two polyclonal antibodies against synthetic oligopeptides comprising amino acid sequences in the human lysosomal protective protein. The first antibody recognized the 54-kDa precursor and the N-terminal sequence of the 32 kDa mature protein subunit, and the second one recognized the precursor and the C terminal sequence of the 20-kDa subunit. In normal fibroblasts, mature protective protein was detected on immunoblotting with these antibodies. Considerable amounts of mature protective protein also were detected in kidney, lung, liver, and spleen, but not in brain from a patient with Gaucher disease. Neither the precursor nor the mature protective protein was detected in cultured fibroblasts, liver or cerebrum from a galactosialidosis patient with protective protein deficiency. PMID- 7999053 TI - Expression, purification, and characterization of porcine leukocyte 12 lipoxygenase produced in the methylotrophic yeast, Pichia pastoris. AB - A cDNA coding for porcine leukocyte 12-lipoxygenase was expressed intracellularly in the methylotrophic yeast Pichia pastoris under the regulatory control of the alcohol oxidase promoter. The recombinant 12-lipoxygenase contained in the yeast cell lysate was soluble, displayed the catalytic properties of the native enzyme, and was recognized by antibodies prepared against native 12-lipoxygenase derived from porcine leukocytes. The catalytically active enzyme of the 100,000 x g supernatant obtained from the yeast lysate was readily purified by immunoaffinity chromatography to near homogeneity. Porcine leukocyte 12-lipoxygenase is the first arachidonic acid oxygenase to be expressed in yeast, an easy, inexpensive, and rapid method of expressing native and site-directed mutants of recombinant proteins. PMID- 7999054 TI - Spermine effect on the binding of casein kinase I to the rat liver mitochondrial structures. AB - The results indicated here, together with those previously reported, show that spermine, ubiquitous polyamine, while promoting the transmembrane translocation of casein kinase II (CKII) across the outer membrane to more internal compartments of rat liver mitochondria, promotes the binding of casein kinase I (CKI) to the external surface of outer mitochondrial membrane but inhibits its spontaneously occurring binding to more internal structures. PMID- 7999056 TI - Molecular cloning of two pigment-dispersing hormone (PDH) precursors in the blue crab Callinectes sapidus reveals a novel member of the PDH neuropeptide family. AB - A cDNA library was established from the eyestalk ganglia of the blue crab Callinectes sapidus. Screening resulted in the isolation of a clone (497 bp excluding poly(A) tail) which encodes a beta-PDH previously found in several crustacean species. It displays high sequence similarity with a clone isolated from an eyestalk cDNA library of the shore crab Carcinus maenas, indicating the close phylogenetic relationship of both species. A second clone (414 bp exclusive of the poly(A) tail) encodes a novel beta-PDH analog which displays 400-fold less potency in crab bioassays. Both cDNAs encode open reading frames of 234 bp for the prepropeptides, consisting of signal peptides, PDH-precursor-related peptides, and PDH sequences. PMID- 7999055 TI - Role of sialic acid on the viscosity of canine tracheal mucin glycoprotein. AB - The role of sialic acid on the viscosity of canine tracheal mucin (CTM) was investigated. The mucin glycoprotein, purified from canine tracheal mucus, was subjected to mild acid hydrolysis with aqueous acetic acid and autohydrolysis in water, in which approximately 50% drop in the relative viscosity (nr) occurred. Carbohydrate compositional analysis before and after mild acid hydrolysis and autohydrolysis showed the complete removal of glycosidically bound sialic acid residues while all other sugar residues (i.e. galactose, N-acetyl galactosamine and N-acetyl glucosamine) remained unaltered, indicating that sialic acid residues are contributing towards the viscosity of CTM to a greater extent. PMID- 7999057 TI - Obese Zucker (fa/fa) rats are resistant to insulin's inhibitory effect on hepatic apo B secretion. AB - Hepatocytes derived from lean Zucker rats have reduced secretion of apo B and lowered cellular apo B in response to a physiologic range of insulin (0.1 nM-10 nM). Effects are attenuated in hepatocytes derived from Zucker obese rats and seen only at higher insulin concentrations (> 100 nM) with a significant shifting of the dose-response curve. Decreased sensitivity and responsiveness of hepatocytes derived from obese rats suggests insulin resistance and dose-response curves are consistent with coexistent binding and post-binding defects. Inability to inhibit hepatic apo B secretion in the presence of short-term high levels of insulin may have important implications to the balance of intestinal and hepatic triglyceride-rich lipoprotein secretion post-prandially. PMID- 7999058 TI - Intracellular mediators of goblet cell degranulation in isolated pancreatic ducts. AB - The involvement of particular intracellular signalling pathways in agonist-evoked degranulation of guinea pig pancreatic duct goblet cells was investigated. Carbachol, vasoactive intestinal peptide (VIP), calcium ionophore A23187, phorbol ester 12-O-tetradecanoylphorbol 13-acetate (TPA), cyclic AMP analogue Sp-5,6-DCl cBIMPS and forskolin each caused degranulation of goblet cells in isolated ducts. Degranulation induced by carbachol was not inhibited by okadaic acid, cytochalasin-D or nocodazole. These results indicate that at least two major signalling pathways are involved in pancreatic duct goblet cell secretion. PMID- 7999059 TI - Limb mesenchymal cells inhibited from undergoing cartilage differentiation by a tumor promoting phorbol ester maintain expression of the homeobox-containing gene Msx1 and fail to exhibit gap junctional communication. AB - Tumor promoting phorbol esters are potent inhibitors of the chondrogenic differentiation of limb mesenchymal cells, but the mechanism by which these agents elicit their antichondrogenic effect is unknown. Here we report that limb mesenchymal cells inhibited from undergoing chondrogenesis by a tumor promoting phorbol ester exhibit deregulated expression of the homeobox-containing gene Msx1, a gene implicated in suppressing differentiation of limb mesenchymal cells, and fail to exhibit the extensive gap junctional intercellular communication that normally occurs at the onset of chondrogenesis. These results suggest that tumor promoting activity of phorbol esters may relate to their ability to modulate the expression of regulatory genes involved in controlling terminal differentiation, as well as to their ability to disrupt the intercellular communication involved in initiating the differentiated phenotype of cells. PMID- 7999060 TI - Spontaneous calcium oscillations in clonal endocrine pancreatic glucagon secreting cells. AB - Measurements of the cytosolic calcium concentration in single cells of the clonal endocrine pancreatic glucagon-secreting cell line INR1 G9 revealed the existence of spontaneous calcium oscillations in 20-70% of these cells. Inhibition of these spontaneous oscillations by thapsigargin as well as the phospholipase C inhibitor U 73122 demonstrated involvement of calcium release from intracellular stores, probably mediated by a high basal activity of phospholipase C. Removal of extracellular calcium but not the L-type calcium channel antagonists verapamil or nifedipine terminated the spontaneous oscillations, suggesting that calcium influx by a pathway distinct from L-type channels contributed to the oscillations. Similar spontaneous calcium oscillations could be the pacemaker of pulsatile glucagon release in endocrine pancreatic A-cells. PMID- 7999061 TI - Cell-type-specific induction of the UL9 gene of HSV-1 by cell signaling pathway. AB - The origin-binding protein, encoded by the UL9 gene of herpes simplex virus-1 (HSV-1), has the properties of an initiator of DNA replication. In this communication, we report that the UL9 promoter contains a cAMP-response element (CRE). Transient expression analyses show that dibutyryl cyclic AMP, known to elevate intracellular cAMP level, can induce the UL9 promoter in a rat pheochromocytoma cell line (PC12) but not in a non-neuronal human cell line (HeLa). Interestingly, a transcription factor that increases expression of a neuropeptide gene by interacting with CRE can also activate the UL9 promoter independent of cell type. Thus, our data suggest that extracellular stimuli, capable of interacting with the signaling pathway in neuronal cells, can activate UL9 gene expression, and different proteins may regulate UL9 expression in different cell types. PMID- 7999062 TI - Demonstration of activin-A in arteriosclerotic lesions. AB - We previously reported that follistatin, an activin-binding protein, is produced in arteriosclerotic lesions. Here, the expression of activin-A which promotes the growth of vascular smooth muscle cells was examined in arteriosclerotic lesions of WHHL (Watanabe heritable hyperlipidemic) rabbits. Activin-A mRNA was detected in normal aorta by reverse transcriptase-polymerase chain reaction using specific primers for activin-A cDNA and was increased remarkably in arteriosclerotic lesions. In addition, using the cloned rabbit activin-A cDNA, RNA probe was prepared and in situ hybridization histochemistry was performed. Activin-A transcripts were detected abundantly in neointima of the diseased artery. Furthermore, immunohistochemistry also detected activin-A at the protein level. These observations suggest that activin-A is a cytokine expressed in arteriosclerotic lesions and might be involved in the pathogenesis of atherosclerosis. PMID- 7999064 TI - Effect of retinoic acid on contraction of collagen gel induced by fibroblasts. AB - Retinoic acid inhibited the contraction of collagen gel containing fibroblasts. Moreover, in its presence fibroblasts extensions were shorter, fewer collagen fibers were recognized, cell adhesiveness was inhibited concentration dependently, and microfilaments appeared to be disrupted, resulting in morphological changes including loss of multipolar cell processes due to changes in cytoskeletal linkages. PMID- 7999063 TI - Motilin synthetic analogues and motilin receptor antagonists. AB - While studying the structure-activity characteristics of motilin with motilin synthetic analogues, two compounds, motilin 1-12 [CH2 NH]3-4 and motilin 1-12 [CH2 NH]10-11, showed high affinity for the motilin receptor combined to a weak contractile activity. The following data suggest that motilin 1-12 [CH2 NH]10-11 is a potent motilin receptor antagonist. It showed a high affinity for the motilin receptor present on membranes of rabbit antrum (pIC50: 8.24 +/- 0.08 for the analogue vs 8.96 +/- 0.02 for the native peptide). When tested in vitro on strips of rabbit duodenum, the dose-response curve to motilin 1-22 was displaced to the right with motilin 1-12 [CH2 NH]10-11 (pIC50: 8.91 +/- 0.06 in presence of saline versus 7.19 +/- 0.40 with the analogue). However, when injected i.v. in dogs, motilin 1-12 [CH2 NH]10-11 was undetectable in the peripheral blood, suggesting enzymatic degradation precluding its use in vivo. PMID- 7999065 TI - Identification as beta-adducin of a protein interacting with rabphilin-3A in the presence of Ca2+ and phosphatidylserine. AB - Rabphilin-3A is a putative target protein for Rab3A small GTP-binding protein implicated in neurotransmitter release. We have previously identified a Rabphilin 3A-interacting protein with a Mr of about 115 kDa in bovine brain. We have attempted here to purify this protein and to determine its primary structure. Amino acid sequence analysis has revealed that this protein is a bovine counterpart of human beta-adducin which is known to be a good substrate for protein kinase C. The Rabphilin-3A-interacting protein also binds to protein kinase C in the presence of Ca2+ and phosphatidylserine. These results indicate that Rabphilin-3A binds to beta-adducin in the presence of Ca2+ and phosphatidylserine. PMID- 7999066 TI - Human immunodeficiency virus type-1 tat enhances interleukin-2 promoter activity through synergism with phorbol ester and calcium-mediated activation of the NF-AT cis-regulatory motif. AB - Interference with T cell activation signals by Human immunodeficiency virus (HIV) gene products is suggested to contribute to the impairment of immune functions observed in AIDS. Interleukin-2 (IL-2) and HIV share common stimulatory signals triggered during T cell activation. The role of HIV tat, which is the main enhancing factor for viral LTR, in the regulation of IL-2 gene transcription has been studied following transient expression of the tat gene in phorbol ester and calcium ionophore-activated Jurkat cells transfected with IL-2 promoter chloramphenicol acetyltransferase reporter constructs. We observed that tat increased the IL-2 promoter transcriptional activity in response to phorbol ester and ionomycin. This tat-dependent synergism mapped to the (-279 to -263 bp) NFAT motif of the IL-2 enhancer, which was sufficient to be transactivated by tat. Our data suggest that tat links T cell activating signals to the shared IL-2 and HIV regulation. This may play a role in the early phase of HIV infection. PMID- 7999067 TI - A rapid and efficient PCR-based method for synthesizing high-molecular-weight multimers of oligonucleotides. AB - We have developed a simple PCR based approach for synthesizing high-molecular weight DNA multimers of short oligonucleotide elements in yields sufficient for preparing DNA affinity columns or for using as probes to detect sequence-specific DNA binding proteins. The technique is rapid, efficient and produces multimers consisting of 30-100 repeating units. PMID- 7999069 TI - Structure of the human hexokinase II gene. AB - Mutations in the gene encoding hexokinase II which catalyzes a key step in glycolysis could contribute to the development of peripheral insulin resistance and lead to non-insulin-dependent diabetes mellitus. As a first step towards screening patients for mutations in this gene, we have determined its structure and the sequence of exon-intron junctions. The human HKII gene is composed of 18 exons that span at least 40 kb, and its organization is highly homologous to that of the rat gene. A hexokinase II processed pseudogene was discovered while screening a human genomic library. The coding sequence of this pseudogene is uninterrupted by introns and contains at least one premature stop codon. PMID- 7999068 TI - Mapping of two phenol sulphotransferase genes, STP and STM, to 16p: candidate genes for Batten disease. AB - The cytosolic phenol sulphotransferase gene (STP) was mapped to a region of chromosome 16, within the interval defined by human-rodent somatic cell hybrid breakpoints CY160(D) and CY12, which contains FRA16E. YAC and cosmid clones from this 16p interval were screened for the presence of STP. Two non-overlapping cosmid contigs were identified which contain STP-like sequences. Sequencing of these STP-like sequences confirmed that STP is contained within contig 343.1 and maps proximal to FRA16E, and that a related sulphotransferase STM, encoding the catecholamine-sulphating enzyme, is contained within contig 55.4 and maps to the adjacent hybrid interval CY12-CY180A. Thus two phenol sulphotransferase genes (STP and STM) have been finely localised to chromosome 16p12.1-p11.2, to the same region as CLN3, the gene for Batten disease. Both genes are therefore candidate genes for Batten disease. PMID- 7999070 TI - Isolation and characterization of a cDNA that codes for a LIM-containing protein which is developmentally regulated in heart. AB - During our human heart cDNA sequencing project, we have obtained a novel cDNA clone which is very similar in DNA and amino acid sequences to a rat/mouse cysteine-rich intestinal protein (1). Sequence analysis has shown that this human cysteine-rich heart protein (hCRHP) is a protein of 77 amino acids and possesses a LIM motif which is considered to be able to bind zinc. Northern blot analyses have shown that its mRNA level in rat heart is regulated developmentally. We have expressed hCRHP in E. coli using pAED4 as the vector and the cDNA was engineered so that the authentic protein is produced. The protein was partially purified and was shown to be a basic protein. PMID- 7999071 TI - A naturally occurring mutation at the second base of codon asparagine 43 in the proposed N-linked glycosylation site of human lipoprotein lipase: in vivo evidence that asparagine 43 is essential for catalysis and secretion. AB - The patient was a 20-year-old male. His fasting plasma triglyceride and cholesterol levels were 1258 mg/dl and 138 mg/dl, respectively. The lipoprotein lipase (LPL) activity and mass from postheparin plasma of the patient were 0.00 mumol/ml/h (normal range: 5.51 +/- 1.12) and 23 ng/ml (normal range: 220 +/- 42), respectively. DNA sequence analysis of the LPL gene from the patient revealed a homozygous nucleotide change: a A-->G transition at nucleotide position 383, resulting in an amino acid substitution of Ser for Asn43, which is believed to be an N-linked glycosylation site of the LPL mature protein. Expression studies of this mutant LPL cDNA produced an inactive LPL protein which was not secreted into the media. PMID- 7999072 TI - Tetrahydrobiopterin as another EDRF in man. AB - Endotoxin and inflammatory cytokines downregulate expression of constitutive nitric oxide synthase (cNOS) in human vascular endothelial cells with concomitant increase of tetrahydrobiopterin synthesis in these cells and parallel upregulation of inducible NOS expression in smooth muscle cells, indicating compartmentalized nitric oxide (NO) production under septic conditions in man. In this report the compartmentalization has been further studied using dual chamber cell cultures with inflammatory activated human endothelial cells. We show that endothelial cells secrete BH4 vectorially into the basal direction thereby providing underlining smooth muscle cells with the cofactor necessary for NO production. Furthermore, by laser Doppler velocimetry we show that intraarterial infusion of BH4 induces strong vasodilatation in man. Consumption of L-arginine and production of cyclic GMP increased and therefore imply NO as second messenger. Thus the discovery of an endothelium-derived factor regulating NOS activity would reconcile the concept of an inflammatory EDRF that is not NO itself but results in NO-dependent vasodilatation in man. PMID- 7999073 TI - Cloning and production of functional active recombinant hepatitis B virus surface antigen binding protein. AB - Endonexin II present on the surface of human hepatocytes has recently been identified as a hepatitis B virus surface antigen (HBsAg) binding protein. A full length cDNA clone encoding human endonexin II was isolated from a human liver cDNA library and was placed under the control of the polyhedrin promoter of Autographa californica nuclear polyhedrosis virus (AcNPV). Infection of Spodoptera frugiperda cells with recombinant virus resulted in the production of high amounts of recombinant protein. This protein has the same molecular weight and iso-electric point as native human endonexin II. It can be easily purified by methods analogous to those described for the native protein. Moreover, the recombinant product binds very efficiently to hepatitis B surface proteins (HBsAg) in a similar fashion as native human endonexin II. PMID- 7999074 TI - The effect of mouse mammary tumor virus receptor activation on mammary epithelial cell sensitivity toward prolactin. AB - Mammary epithelial cells infected with the mouse mammary tumor virus (MMTV) require less than one-half the concentration of prolactin to elicit alpha lactalbumin production than uninfected tissue (EC50 = 89 +/- 10 ng/ml vs. 206 ng/ml, respectively). Furthermore, stimulating antibodies to the cellular receptor for MMTV halved the prolactin requirement of MMTV-tissue, while MMTV antibodies that sequestered secreted MMTV increased the prolactin requirement in MMTV+ tissue. These data suggest that the effect of MMTV on mammary epithelial sensitivity toward prolactin is being mediated by its interaction with a cell surface receptor. PMID- 7999075 TI - An NLS is sufficient to engage facilitated translocation by the nuclear pore complex and subsequent intranuclear binding. AB - We investigated the nuclear transport of a fusion protein consisting of a nuclear localization signal linked to beta-galactosidase, normally a cytoplasmic protein. We microinjected the radiolabeled fusion protein into the cytoplasm of living Xenopus oocytes or supplied it directly to the surface of the oil-isolated oocyte nucleus and measured its transport into the nucleus. Our data confirm that a nuclear localization signal is sufficient to entrain a protein's facilitated transport through the nuclear pore complex and its subsequent nuclear accumulation. Moreover, nuclear envelope micropuncture experiments determine that the fusion protein's accumulation results from its intranuclear binding, demonstrating that no specific region of a transported protein--other than the nuclear localization signal itself--is required for facilitated transport and intranuclear binding. Finally, we present evidence that the intranuclear binding of a transported protein requires not only its nuclear localization signal, but also its prior facilitated transport through the nuclear pore complex. PMID- 7999076 TI - Cloning and sequence of the human type II IMP dehydrogenase gene. AB - Human type II inosine 5'-monophosphate dehydrogenase (EC 1.1.1.205) is the rate limiting enzyme in de novo guanine nucleotide biosynthesis. Regulated inosine 5' monophosphate dehydrogenase activity is associated with cellular proliferation, transformation, and differentiation. We cloned and sequenced the entire gene for type II inosine 5'-monophosphate dehydrogenase and here provide details regarding the organization of the gene and its transcriptional start sites. The gene spans approximately 5 kb and is disrupted by 12 introns. The transcriptional start sites were determined by S1 nuclease mapping to be somewhat heterogeneous but predominated at 102 and 85 nucleotides from the translational initiation codon. PMID- 7999077 TI - Co-occurrence of CArG boxes and TCF sites within viral genomes. AB - The transcription factor SRF is involved in the transduction of extracellular signals into nuclear responses, often in conjunction with ternary complex factors (TCFs). Here we report the identification of CArG box SRF binding-sites, and neighboring TCF binding-sites, in viral genomes. SRF binds and recruits TCFs to CMV, RSV and HTLV-1 viral genomes. At least one of two specific CArG boxes occurred in cytomegaloviruses in the 5' proximal region of the major immediate early gene, one always accompanied by a TCF site. This conservation was striking since neither the flanking sequences nor the spacing to the CAP site were conserved. Thus the ubiquitous SRF and TCF molecules may control events in the life cycle of viruses. PMID- 7999078 TI - Two novel mutations in the vasopressin V2 receptor gene in patients with congenital nephrogenic diabetes insipidus. AB - Families with congenital nephrogenic diabetes insipidus were analyzed with regard to mutations in the vasopressin V2 receptor gene. Family 1 shows an X-chromosomal recessive inheritance of the disease over 4 generations. A patient from this family was found to have a T-->A transversion at nucleotide 1095, predictive for a substitution of serine 167 (which is highly conserved among G-protein-coupled receptors), by threonine. Both the mutant and the normal allele were detected in the maternal genome. The patient's healthy brother was homozygous for the normal allele. The patient from family 2 showed a T-->C transition at nucleotide 727, predictive for a substitution of leucine 44 by proline. Analysis of the maternal genome revealed homozygosity for the normal allele. Thus a de novo mutation seems to have occurred. The nature and site of the mutation in family 2 suggest that it is responsible for the patient's disease. PMID- 7999079 TI - The nucleotide and deduced amino-acid sequences of a cDNA encoding lactate dehydrogenase from Caenorhabditis elegans: the evolutionary relationships of lactate dehydrogenases from mammals, birds, amphibian, fish, nematode, plants, bacteria, mycoplasma, and plasmodium. AB - The nucleotide and deduced amino-acid sequences of a cDNA encoding L-lactate dehydrogenase (LDH) from nematode, Caenorhabditis elegans, were reported. This first invertebrate LDH sequence of 333 amino acids, including the initiation methionine, exhibits 63% identity with that of the most primitive vertebrate lamprey. The evolutionary relationships among 36 LDH isozymes from mammals, birds, amphibian, fish, nematode, plants, bacteria, mycoplasma and plasmodium were analyzed. The invertebrate nematode LDH is evolutionarily positioned between plant LDH and mammalian testicular LDH-C isozymes. The mammalian LDH-C isozyme appears to have arisen after the invertebrate LDH, but prior to the divergence of vertebrate LDH-A (muscle) and LDH-B (heart) isozymes as described previously. PMID- 7999080 TI - Effects of inhibiting transglutaminase during egg fertilization and development. AB - Transglutaminase inhibitor (1,3,4,5-tetramethyl-2-[(2-oxopropyl)thio]imidazolium chloride or L-682777) affected the appearance of the fertilization envelope (FE) and subsequent development in Sphaerechinus granularis and Arbacia punctulata in a concentration-dependent manner. Abnormalities were first visible in forming FE's at the lowest concentration (0.001 mM) of the inhibitor used. The wrinkled appearance of FE's suggested that the treatment prevented the I-T transition, whereas the finding of numerous denuded cells and empty FE's indicated that the inhibitor acted by rendering the FE's very fragile. Cell division by the 2-cell stage was also affected by this active-site-directed transglutaminase inhibitor. With 0.05 mM of the inhibitor, about 50% of all cells were polynucleated. In view of earlier findings that other transglutaminase inhibitors can produce abnormalities with regard to FE wrinkling and deranged cell division, it can be suggested that different forms of transglutaminases might be involved at various stages in embryonic development. PMID- 7999081 TI - PI 3-kinase activation is required for insulin stimulation of glucose transport into L6 myotubes. AB - Phosphatidylinositol 3-kinase (PI 3-kinase) is acutely stimulated by insulin but its role in regulating glucose metabolism is still not fully understood. Insulin acutely stimulates glucose transport into L6 myotubes approximately 2-fold, and activates PI 3-kinase activity 2 to 3-fold. Wortmannin, an inhibitor of PI 3 kinase, blocked insulin stimulation of 2-deoxyglucose transport into the myotubes in a time and dose-dependent manner. Inhibition was observed within 5 minutes and was complete by 30 minutes. The IC50 for this inhibition was approximately 10 nM; almost complete inhibition was observed at 100 nM. Similarly, insulin stimulation of PI 3-kinase activity was inhibited by wortmannin in a dose-dependent manner. The insulinmimetic vanadate activated hexose transport into the myotubes to more than 50% of the maximal level attained with insulin. Only approximately 60% of vanadate-activated glucose transport was inhibited by maximal wortmannin concentrations. It is concluded that insulin activation of PI 3-kinase is necessary for stimulation of glucose transport into L6 muscle cells. In contrast, vanadate appears to augment transport by acting upon PI 3-kinase-dependent and independent pathways. PMID- 7999082 TI - Basic fibroblast growth factor sense (FGF) and antisense (gfg) RNA transcripts are expressed in unfertilized human oocytes and in differentiated adult tissues. AB - Basic fibroblast growth factor (bFGF) is a highly conserved and ubiquitously distributed mitogen. In amphibian oocytes bFGF mRNA is regulated post transcriptionally by interaction with an antisense RNA transcript. We used reverse transcription-polymerase chain reaction (RT-PCR) and Northern hybridization to determine the presence of bFGF and its antisense RNA (gfg) in unfertilized human oocytes and postnatal differentiated tissues. BFGF and gfg transcripts were co-expressed in many tissues, with bFGF transcripts (7, 3.7 and 1.8 kb) being more abundant than the gfg transcript (1.5 kb) in 8 of 16 tissues examined. Sense and antisense expression was approximately equal in kidney and colon, while in heart, liver, skeletal muscle and testis gfg transcripts predominated. RT-PCR demonstrated the presence of bFGF and gfg transcripts in unfertilized oocytes where the antisense transcript was present in excess of the sense transcript. These findings suggest a role for gfg in regulation of bFGF expression. PMID- 7999084 TI - Metallothionein-II and ferritin H mRNA levels are increased in arsenite-exposed HeLa cells. AB - Arsenite is extremely toxic and, though non-mutagenic, is a carcinogen. To determine the effects of arsenite on changes in cell physiology, we searched for genes in HeLa cells whose mRNAs are more abundant after cellular exposure to arsenite. A cDNA subtraction was performed between cDNA synthesized from HeLa cells grown in the absence and presence of 5 microM sodium arsenite. Isolation and sequencing of three clones that showed a higher hybridization signal to RNA from arsenite-exposed cells, versus unexposed cells, revealed that two of the cDNAs coded for human ferritin H chain and the other coded for metallothionein II. These results suggest the possibility that arsenite exposure may lead to increased levels of oxygen radicals, which augmented metallothionein and ferritin can act to detoxify. PMID- 7999085 TI - Biophysical and pharmacological properties of large conductance Ca(2+)-activated K+ channels in N1E-115 cells. AB - The large conductance Ca(2+)-activated K+ channels in differentiated mouse neuroblastoma N1E-115 cells have been studied using patch-clamp single-channel current recording in excised membrane patches. These channels displayed a unitary conductance of 200 pS under symmetrical K+ concentrations. Effects of blockade by TEA+, Cs+ and Ba2+ were different and argued for distinct action mechanisms. The open probability of these channels increased with increasing internal calcium and membrane potential. Maximum sensitivity of these channels ranged over physiological variations of internal calcium at membrane potentials close to zero, suggesting a physiological role for these channels in regulating the membrane potential and Ca2+ influx through voltage-dependent Ca2+ channels. PMID- 7999083 TI - Effect of thyrotropin and adenosine on inositol phospholipids pathway in human thyroid in Graves' disease. AB - The present study demonstrates that exposure of human thyroid slices obtained during planned surgery of patients with Graves' disease to thyrotropin stimulates the phospholipid metabolism as measured by an increase incorporation of 2-myo [3H]-inositol into phosphatidylinositol and poliphosphatidylinositides and the generation of InsP3. The results indicate that adenosine, probably via the A1 type of P1 receptor, modulates these actions, both incorporation of labelled substrate into thyroid slices as well as its metabolism to active compounds which could play a role in a cell signalling system. These observations indicate the significance of the phosphatidilinositol pathway in signal transmission of both, thyrotropin as well as P1 purinergic receptors agonists in human thyroid. PMID- 7999086 TI - 5'-flanking region surrounding a human cytosolic phospholipase A2 gene. AB - The 5'-flanking region and the first four exons of a gene encoding human cytosolic phospholipase A2 (cPLA2) were isolated from a human lambda EMBL3 genomic library and sequenced. The 5'-flanking region is characterized by CA repeats, one of microsatellites. The analysis of the 5'-flanking region with transcription factor database suggests the existence of the transcription factor binding sites such as NF-kappa B, NF-IL6, AP-1, AP-2, and PEA3. These factors are well known to be induced or activated by the reagents (tumor necrosis factor alpha, interleukin-1, epidermal growth factor, and phorbol myristate acetate) reported as the inducers of a cPLA2 gene. PMID- 7999087 TI - Stimulation of cell-mediated low-density lipoprotein oxidative modification by oncostatin M. AB - The effect of oncostatin M on low-density lipoprotein oxidative modification by human monocytes or murine endothelial cells was studied by determination of the lipid peroxidation products content and the electrophoretic mobility of the particle. In the range of concentrations from 10 to 30 ng/ml, oncostatin M induced a dose-dependent increase in LDL oxidation. The LDL degradation by J774 macrophage-like cells was also stimulated. Preincubation of cells with oncostatin M also enhanced the subsequent LDL modification. This effect was accompanied by a parallel increase in superoxide anion release by cells. Since oncostatin M is produced by immune cells, the described effect suggests a relationship between infection, inflammation and LDL oxidative modification. PMID- 7999088 TI - The relationship between size of a presecretory protein and extent of signal recognition-particle-mediated arrest of its translation. AB - Small eukaryotic presecretory proteins, such as preprocecropinA, prepromelittin, and prepropeptideGLa, are transported into mammalian microsomes both with the aid of ribosome and signal recognition particle (SRP) and independently of these ribonucleoprotein particles. Typically, synthetic extensions of these precursor proteins show the phenotype of naturally occurring large presecretory proteins. However, it was shown that small truncated forms of naturally occurring large presecretory proteins are not transport competent or transport competent only in the presence of the two ribonucleoprotein particles. In order to directly address this apparent paradox, we studied the sensitivities of nascent polypeptide chains, related to preprocecropinA and prepromelittin, to SRP-mediated arrest of elongation and compared them with synthetic extensions of various length. PMID- 7999089 TI - Characterization of the gene for human neutrophil-activating peptide 78 (ENA-78). AB - The genomic DNA for ENA-78 has been obtained from a human chromosome 4 flow sorted cosmid library. Three out of 25,000 screened single colonies yielded the same 2.2-kB EcoRI ENA-78 gene fragment. A similar size fragment was observed on genomic southern blots, suggesting the presence of a single ENA-78 gene. The transcriptional start site was localized using a 5' RACE protocol on first strand cDNA prepared from stimulated alveolar type-II epithelial cell (A549) poly(A) mRNA. The ENA-78 gene contains four exons and three introns and the open reading frame of 342 nucleotides encodes for a protein of total 114 amino acids. The 5' flanking region contains potential binding sites for several nuclear factors such as AP-2, NF-kappa B, and interferon regulatory factor-1. PMID- 7999090 TI - Use of photoacoustic Fourier-transform infrared spectroscopy to study phosphates in proteins. AB - Photoacoustic Fourier-transform infrared spectroscopy was used to study phosphoamino acids and phosphoproteins. Using this method, we have found that the spectral properties of phosphate esters depend on the nature of the linkage, pH, and binding of metal ion. At high pH values, dianionic symmetric stretching of phosphotyrosine and phosphoserine occurs at 984 and 974 reciprocal centimeters, respectively. Analysis of the IR bands of bound phosphate in phosvitin at different pH values gives the pKa value for the esterified phosphates. Addition of aluminum ions to phosvitin at different pH values causes a shift in the phosphate band consistent with a direct binding of aluminum ions to the esterified phosphate. The phosphate signal for 40 micrograms of Pepsin (1 P/mole) is detectable by this method. PMID- 7999092 TI - In vivo imaging of the interior of Tradescantia zebrina leaves by optical cross correlation interferometry. AB - Using optical correlation interferometry, a novel method for plant sciences, we in imaged in vivo the z-direction, perpendicular to the leaf surface, through Tradescantia zebrina leaves. Non-invasively we determined number of major cell layers, followed the time sequence of decrease in cell z-axis after exposure of tissues to high salt, and observed disruption of cells caused by freezing and thawing. PMID- 7999091 TI - Human adipocyte apoptosis occurs in malignancy. AB - Rapid weight loss is frequently seen in malignancy. This weight loss is considered to result from enhanced lipolysis. Here, we show that adipocyte deletion by apoptosis, demonstrated by electron microscopy and DNA gel electrophoresis, occurs in some patients. Adipocyte apoptosis could not be demonstrated in patients without malignancy. These findings suggest that fat cell loss by apoptosis plays a role in malignancy-associated weight loss. PMID- 7999093 TI - Molecular cloning of the human angiotensin II type 2 receptor cDNA. AB - A human adult lung cDNA library was screened and one full-length human angiotensin II type 2 receptor (hAT2R) clone was isolated and characterized. The hAT2R cDNA clone contains a 1089-base-pair open reading frame which encodes a protein of 363 amino acid residues. The hAT2R is approximately 92% identical in sequence to the rat and mouse AT2R sequences. Specific binding of [125I]CGP42112A was demonstrated in membranes from COS-7 cells transiently transfected with the hAT2R cDNA. Scatchard analysis and ligand displacement profiles were typical of the AT2R. Northern analysis demonstrated that the hAT2R mRNA was abundantly expressed in human adult lung and in human fetal kidney. Additionally, the hAT2R mRNA was just detectable in human adult heart and aorta. In contrast, the rat AT2R mRNA was abundantly expressed in the rat brain and just detectable in the rat lung. PMID- 7999094 TI - 3,5,3'-Triiodo-L-thyronine induces cardiac myocyte differentiation but not neuronal differentiation in P19 teratocarcinoma cells in a dose dependent manner. AB - P19 teratocarcinoma cells differentiate into neurons or muscle when treated with varying doses of retinoic acid, dimethylsulfoxide, thioguanine or butyrate. We induced cardiac differentiation in P19 cells by treating them with 3,5,3'-Triiodo L-Thyronine (T3). P19 cells received doses of T3 ranging from 30 pM to 300 nM. The beating colonies were counted, and a dose response curve showed that the optimal concentration of T3 was 30 nM. The colonies beat rhythmically for 4-6 weeks, and the cardiac myocytes showed clearly evident cardiac-specific organelles such as nexuses and atrial granules. No evidence of neuronal or skeletal muscle differentiation was seen with any of the concentrations of T3 used. Reverse transcription-polymerase chain reaction showed these cells to express the cardiac ventricular specific marker myosin light chain 2V. T3 is capable of inducing P19 cells to differentiate, in a dose related manner, into spontaneously beating cardiac myocytes identified as such on the basis of ultrastructural criteria. The induction of differentiation is accompanied by expression of cardiac-specific genes. These findings suggest that perhaps genes bearing thyroid response elements in their promoter regions play an important role in the cardiac differentiation induced by T3 in P19 teratocarcinoma cells. PMID- 7999095 TI - Tax-induced HTLV-I LTR transcriptional activation is modulated by phosphorylation. AB - We studied the effect of protein phosphatase and kinase inhibitors on Tax mediated transcription of constructs carrying the reporter gene chloramphenicol acetyl transferase under the control of either the full-length LTR of HTLV-I or three copies of the tax-responsive 21-bp repeats. We observed that treatment with okadaic acid, which inhibits the serine/threonine protein phosphatases type 1 and 2A, reduced HTLV-I LTR transcriptional activation in MT2 and K562 cells; on the contrary, the enhancer activity of the 21-bp sequences was significantly increased in both cell lines; treatment with the protein kinase C inhibitor H-7 blocked Tax-mediated transcription of both constructs. We also found that treatment with sodium orthovanadate, a tyrosine phosphatase inhibitor, reduced Tax-mediated activation of both plasmids. These findings indicated that specific serine/threonine phosphorylation events are required for Tax-mediated HTLV-I LTR activation and also suggested that phosphorylation at tyrosine residues is involved in this process. PMID- 7999096 TI - Parathyroid hormone and 1,25-dihydroxyvitamin D synergistically induce the 1,25 dihydroxyvitamin D-24-hydroxylase in rat UMR-106 osteoblast-like cells. AB - We have studied the effect of parathyroid hormone (PTH) and 1,25-dihydroxyvitamin D3 (1,25(OH)2D) on the expression of the 1,25-dihydroxyvitamin D-24-hydroxylase (24-hydroxylase) in rat UMR-106 osteoblastic cells. 1,25(OH)2D (10(-7) M) alone produced a gradual increase in mRNA levels of the 24-hydroxylase cytochrome P450 component (P450cc24) during 12 hours of incubation. Rat PTH 1-34 (250 nM) in the presence of 1,25(OH)2D further increased P450cc24 mRNA levels 7-10 fold after 3 hours. PTH alone had no significant effect. The action of PTH was mimicked by forskolin but not by phorbol ester. The 24-hydroxylase enzymatic activity in UMR cells was increased over 5-fold by PTH and 1,25(OH)2D together compared to 1,25(OH)2D alone after 6 hours. This synergistic regulation of the 24-hydroxylase in bone cells is in contrast to the regulation in the kidney, where PTH and 1,25(OH)2D have opposite effects on 24-hydroxylase expression. PMID- 7999097 TI - Isolation, characterization and amino acid sequence of echicetin beta subunit, a specific inhibitor of von Willebrand factor and thrombin interaction with glycoprotein Ib. AB - Echicetin is a dimeric protein isolated from the venom of Echis carinatus that is a potent inhibitor of von Willebrand Factor and thrombin binding to glycoprotein Ib. Here, we report isolation and amino acid sequence of the beta subunit of echicetin that contains 123 amino acids, including 7 cysteines, and shows similarity with amino acid sequences of botrocetin and Factor IXa/Xa binding protein. We provide evidence that biological activity of echicetin which resides in this beta subunit is relatively resistant to reduction of the molecule. PMID- 7999098 TI - Effect of acute diabetes on rat hepatic glucose-6-phosphatase activity and its messenger RNA level. AB - Glucose-6-phosphatase catalyzes the final step of glucose production by liver and kidney. Though its strategic position has sparked interest in its regulation, difficulty with isolating a pure, stable enzyme has slowed progress. Virtually all previous work examining the physiologic regulation of this enzyme has relied on estimates of glucose-6-phosphatase activity in crude microsome preparations. The recent cloning of human and murine glucose-6-phosphatase cDNAs has now allowed study of its mRNA expression. We studied the effect of acute, streptozotocin-induced diabetes on hepatic microsomal glucose-6-phosphatase activity and mRNA expression in young (89 +/- 3 g), juvenile (304 +/- 4 g) and adult (512 +/- 10 g) rats. In control rats, mRNA expression and enzyme activity was similar among the three age groups. Streptozotocin-induced diabetes significantly increased the enzyme activities in both intact and triton-treated microsomes in all groups of rats (p < 0.001). Glucose-6-phosphatase mRNA expression was increased in the diabetic rats as well (p < 0.0001). Blood glucose concentrations correlated significantly with glucose-6-phosphatase mRNA level (p < 0.005) and both intact (p < 0.002) and triton-treated (p < 0.001) microsomal glucose-6-phosphatase activity. Both intact and triton-treated microsomal glucose 6-phosphatase activity correlated with mRNA level (p < 0.001, for each). We conclude that acute streptozotocin-diabetes increase expression of glucose-6 phosphatase mRNA and this contributes to the increased glucose-6-phosphatase activity seen with diabetes mellitus. PMID- 7999099 TI - Evolutionary conservation and molecular cloning of the recombinase activating gene 1. AB - A 700-bp fragment of the recombinase activating gene 1 (RAG-1) was cloned from several evolutionarily distant (sandbar shark, paddlefish, goldfish, axolotl and pig) species using PCR. The nucleotide and deduced amino acid sequences revealed a highly conserved region that has remained essentially unaltered during 400 million years of evolution; e.g., shark and human sequences were 75% identical at the nucleic acid level and 87% as protein. The RAG-1 mRNA levels in the shark were analyzed using semi-quantitative PCR to reveal expression patterns contrary to normal mammalian expression. These results establish that the genetic mechanisms for Ig gene rearrangement are present in all extant gnathanstomes. PMID- 7999100 TI - The overexpression of insulin receptor makes CHO cells resistant to the action of IGF-1: role of IRS-1. AB - We investigated the influence of the relative abundance of insulin and IGF-1 receptors on cellular growth, by measuring the stimulation of c-fos expression and of H3-thymidine incorporation into DNA by insulin and IGF-1 in CHO cells overexpressing insulin Receptor (CHO-IR). We found that CHO-IR cells were resistant to the action of IGF-1, but were more responsive to insulin, compared to parental clone. This result suggest the presence of a limiting step, distal to the IGF-1 receptor, in the transduction pathway. To address this question we measured the IGF-1 effect on c-fos expression in CHO-IR cells, transiently transfected with the cDNA for IRS-1, the common intracellular substrate for both insulin and IGF-1 receptors (CHO-IR/IRS-1 cells). In these cells IGF-1 stimulated a 10 fold higher c-fos expression compared to CHO-IR cells. These results suggest that the abundance of IRS-1, relative to the number of insulin and IGF-1 receptors, represents a limiting step for the intracellular transduction of insulin and IGF-1 biological messages. PMID- 7999101 TI - Interaction of fibronectin (FN) cell binding fragments and interleukin-8 (IL-8) in regulating neutrophil chemotaxis. AB - This study investigated the possible interaction of FN fragments in regulating IL 8-mediated neutrophil chemotaxis in vitro using Neuroprobe microchambers. Human neutrophil suspensions were incubated with purified FN fragments or an RGD containing peptide and allowed to migrate in response to chemotactically active concentrations of human recombinant IL-8. The 120-kD fragment of FN containing the RGD sequence or an RGD peptide (GRGDSP) inhibited IL-8-mediated neutrophil chemotaxis; however, these RGD peptides did not inhibit neutrophil chemotaxis in response to other chemotactic agents. Furthermore, FN fragments not containing the RGD sequence had no effect on IL-8-mediated chemotaxis. These data suggest that directed migration of neutrophils in response to IL-8 is inhibited in the presence of cell-binding fragments of FN and may represent a local mechanism for terminating neutrophil migration at areas of tissue injury. PMID- 7999102 TI - The endoplasmic reticulum-Golgi system is a major site of plastoquinone synthesis in spinach leaves. AB - Plastoquinone biosynthesis was recently found to be enriched in the microsomal fraction of spinach leaves. Since it is generally assumed that this lipid may predominantly be synthesized in the chloroplast envelope we have prepared total microsomes, containing both endoplasmic reticulum and Golgi membranes, and chloroplast envelopes. Marker enzymes and lipid content showed no significant cross-contamination. Nonaprenyl-2-methylquinol transferase, participating in plastoquinone synthesis, was found in the microsomes but was absent from the chloroplast envelopes and thylakoid membranes. Nonaprenyl-4-hydroxybenzoate transferase activity, an enzyme of ubiquinone biosynthetic system, in microsomes exceeded more than 10 times that found in chloroplast envelopes. The result indicates that in plants plastoquinone is synthesized in the endoplasmic reticulum-Golgi system and transported to the chloroplasts. PMID- 7999103 TI - GDP-ribosyl cyclase activity as a measure of CD38 induction by retinoic acid in HL-60 cells. AB - Retinoic acid (RA) treatment of HL-60 cells induces surface expression of CD38. This lymphocytic antigen is also a novel bifunctional enzyme catalyzing the synthesis and hydrolysis of cyclic ADP-ribose (cADPR), a Ca2+ mobilizing metabolite of NAD+. The synthetic activity of CD38 is very difficult to detect because of the concurrent hydrolytic activity. In this study, a Ca2+ release assay capable of detecting submicromolar concentrations of cADPR was used to demonstrate the induction of ADP-ribosyl cyclase activity in HL-60 cells by RA. Concomitantly, cADPR hydrolase activity was also increased. The results were further substantiated by using a newly developed assay for GDP-ribosyl cyclase activity. This assay uses NGD+ as substrate instead of NAD+. The resulting fluorescent product, cyclic GDP-ribose, is resistant to hydrolysis and accumulates, making it a highly sensitive and convenient assay for CD38-like enzymes. PMID- 7999104 TI - Biological activity and phosphorylation sites of the bacterially expressed cytosolic domain of the KDR VEGF-receptor. AB - Vascular endothelial growth factor (VEGF) is a potent angiogenic factor which binds to two structurally similar receptor tyrosine kinases, KDR and FLT1. Towards the goal of clarifying the signal transduction pathways by which VEGF activates endothelial cells, we expressed in bacteria an enzymatically active form of the cytosolic domain of the KDR receptor. The expressed protein undergoes autophosphorylation in both bacterial cells and in its purified form. Using peptide mapping and sequencing of peptides, we identified four tyrosine residues that are phosphorylated corresponding to residues 951, 996, 1054, and 1059 of the KDR protein. The location of the phosphorylated residues in the bacterially expressed protein, and/or the consensus sequences around these sites, suggest they may be identical to the phosphorylated sites of KDR in mammalian cells. PMID- 7999106 TI - Inositol(1,4,5)trisphosphate production in plant cells: stimulation by the venom peptides, melittin and mastoparan. AB - The ability of the amphiphilic peptides, melittin and mastoparan, to modulate the production of inositol(1,4,5)trisphosphate in cultured plant (Daucus carota L.) cells was investigated. When added to intact cells melittin and mastoparan caused a rapid and dose-dependent increase in inositol(1,4,5)trisphosphate concentrations. In isolated protoplasts, inositol(1,4,5)trisphosphate levels were 12- to 16-fold higher than in the corresponding cells and neither melittin nor mastoparan was able to significantly affect inositol(1,4,5)trisphosphate production. Melittin and mastoparan had a strong inhibitory effect (IC50: 20 microM) on the activity of polyphosphoinositide-specific phospholipase C in purified plasma membranes. These results demonstrate that the plant phosphoinositide system can be activated by amphiphilic peptides in a manner analogous to that observed in specialized mammalian cells but that important functional components are altered, or lost, by the disruption of the intact cell state. PMID- 7999105 TI - c-erbB-2 gene product associates with catenins in human cancer cells. AB - Phosphorylation of beta-catenin, an intracytoplasmic cadherin-binding protein, causes disruption of the cadherin-mediated cell adhesion system in cancer cells. A 185-kDa phosphorylated protein, identified as the c-erbB-2 gene product, was co immunoprecipitated with the E-cadherin-catenin complex. Association of the c-erbB 2 gene product with the cadherin-catenin complex was proven to be mediated through beta-catenin and plakoglobin using an in vitro protein-protein precipitation system. These results indicate that the c-erbB-2 gene product associates with catenins and may regulate the cell adhesion and invasive growth of cancer. PMID- 7999107 TI - Potentiation of K252a, a protein kinase inhibitor-induced polyploidization by cAMP in cultured fibrosarcoma cell line. AB - We found that K252a, a potent inhibitor of protein kinases (PK), induced DNA re replication of Meth-A cells, i.e., DNA synthesis at a higher DNA ploidy without undergoing cytokinesis (polyploidization). The K252a-induced polyploidization was inhibited by phorbol 12-myristate 13-acetate (PMA), a protein kinase C (PKC) activator, suggesting that the polyploidization is caused through inhibition of PKC. By contrast, the polyploidization was potentiated by adenosine 3':5'-cyclic monophosphate (cAMP), a cAMP-dependent protein kinase (PKA) activator. These findings suggest that the cAMP-dependent signaling pathway and diacylglycerol (DAG)-dependent signaling pathway play an important role in regulating the induction of polyploidization in Meth-A cells, through a possible "cross-talk" between the two pathways. PMID- 7999108 TI - The light chain of botulinum neurotoxin forms channels in a lipid membrane. AB - The ability of botulinum neurotoxin and its isolated subunits, the heavy and light chains, to bind to a lipid membrane and to form channels in the membrane was examined. At pH 4.0, the neurotoxin caused aggregation of calcein-containing liposomes, providing evidence of binding of the neurotoxin to the surface of the outer lipid membrane. Aggregation was followed by the release of calcein, as a result of the formation of channels. The heavy chain evoked the same responses as those of the neurotoxin. The light chain did not cause aggregation of the liposomes but did evoke the release of calcein. The channel-forming ability of the light chain appeared to be higher than that of the neurotoxin or the heavy chain. This novel property of the light chain may help us to understand the mechanism of action of botulinum neurotoxin. PMID- 7999109 TI - Iminodipeptides containing proline with C-terminal and N-terminal residues prime the stimulation of human neutrophil superoxide generation by fMLP. AB - Preincubation of human peripheral blood polymophonuclear leukocytes with an iminodipeptide containing proline at the C-terminus and/or N-terminus, Pro-Pro, Gly-Pro, Pro-Gly, Ala-Pro and Pro-Ala, significantly enhanced N-formyl-methionyl leucyl-phenylalanine-induced superoxide generation in a concentration-dependent manner. The iminodipeptide with C-terminal proline showed higher effect than that of the counterpart with N-terminal proline. These iminodipeptides also enhanced the superoxide generation induced by opsonized zymosan but not that induced by arachidonic acid or phorbol myristate acetate. Tyrosyl phosphorylation of the 45 kDa protein occurred in parallel with the iminodipeptide-dependent enhancement of superoxide generation in neutrophil. PMID- 7999111 TI - Correlation between mitochondrial DNA 4977-bp deletion and respiratory chain enzyme activities in aging human skeletal muscles. AB - The content of the mitochondrial DNA 4977-bp deletion and the respiratory chain enzyme activities were determined in the same human skeletal muscle specimens. A direct correlation between damage to mtDNA and bioenergetic deficiency was observed. The time-course of the appearance of the mtDNA deletion was followed. The highest percentage of mtDNA-deleted molecules was 0.26% and it was found in the eighties which corresponds to the age of the major reduction in the respiratory chain enzyme activities. Two samples with very low mitochondrial respiratory enzyme activities exhibited much higher levels of deletion compared to the similar age counterparts. Given, however, the low absolute level of the deletion also in these samples, we suggest that damage to the respiratory chain complexes, especially complex IV, might be the cause more than the effect of the increased number of mtDNA molecules bearing deletions in aged human skeletal muscle. PMID- 7999110 TI - Vascular actions of C-type natriuretic peptide in isolated porcine coronary arteries and coronary vascular smooth muscle cells. AB - C-type natriuretic (CNP) caused concentration-dependent relaxations in porcine coronary arteries with a maximal relaxation (10(-6)M) of 46%. Relaxations to CNP in isolated coronary arteries were significantly attenuated with potassium channel antagonists charybdotoxin (10(-7)M) and glibenclamide (10(-7)M). Membrane potential and K+ currents were measured in enzymatically dissociated smooth muscle cells from porcine coronary arteries with patch-clamp techniques in a whole-cell mode (n = 5). CNP caused K+ channel activation and membrane hyperpolarization in a dose-dependent manner. This hyperpolarization was markedly suppressed by the potassium channel inhibitor tetraethylammonium (TEA, 5 mM). These results demonstrate that CNP relaxes porcine coronary arterial smooth muscle by hyperpolarization of vascular smooth muscle through potassium channel stimulation. PMID- 7999112 TI - Prompt glycosylation of calreticulin is independent of Ca2+ homeostasis. AB - Selective glycosylation of "prompt" stress glycoproteins (P-SG), mainly P-SG67 and P-SG64 (M(r) of 64,000, pI = 5.1), occurs immediately during acute heat stress. In the present study, P-SG64 was purified by sequential gel filtration, anion-exchange, affinity chromatography, and two-dimensional isoelectric focusing/SDS-PAGE. Purified P-SG64 was further characterized by microsequencing of a peptide fragment, PT-61, which showed a 100% sequence homology with calreticulin, suggesting that P-SG64 is identical to calreticulin. PT-61 also showed 55%, 58% and 63% sequence homologies with calnexin, HIV-1 gp120 and HIV-2 envelope polyprotein, respectively. 45Ca2+ overlay studies confirmed Ca(2+) binding of P-SG64. P-SG67 was also recently identified as calreticulin (8), which suggests that CHO cells either have two isoforms of calreticulin or express variable states of calreticulin glycosylation during acute heat stress. The role of intracellular Ca2+ ([Ca2+]i) during heat-induced "prompt" glycosylation was also examined and indicated an 8-fold increase in [Ca2+]i. Chelation of this increased cytoplasmic Ca2+ by BAPTA reduced glycosylation of P-SG67/P SG64/calreticulin only by approximately 20%. This observation suggests that altered [Ca2+]i homeostasis is not directly linked to calreticulin glycosylation, instead, heat-induced calreticulin glycosylation is a Ca(2+)-independent effect. PMID- 7999113 TI - Eotaxin: cloning of an eosinophil chemoattractant cytokine and increased mRNA expression in allergen-challenged guinea-pig lungs. AB - Eotaxin was recently identified as the major eosinophil chemoattractant in bronchoalveolar lavage fluid obtained 3h after allergen challenge of sensitised guinea-pigs. We now report the cDNA cloning of this C-C chemokine. The 777 base pair clone, pEo3122, consists of a 40 base 5' untranslated region, an open reading frame of 288 bases predicting a 73 amino acid mature protein plus a 23 amino acid signal peptide, and a 3' untranslated region of 449 bases containing a poly A tail. Northern blot analysis showed eotaxin mRNA in the lungs of naive and sensitised guinea-pigs, which was considerably increased after allergen challenge. Eotaxin may be an important mediator of eosinophil accumulation and activation in allergic reactions. As eotaxin stimulates human eosinophils, this chemokine and related molecules may be involved in human diseases such as asthma where eosinophil accumulation is a prominent feature. PMID- 7999114 TI - Cyclic strain stimulates dephosphorylation of the 20kDa regulatory myosin light chain in vascular smooth muscle cells. AB - The role of cyclic strain in the regulation of 20 kDa myosin light chain phosphorylation (MLC20) in cultured smooth muscle cells (SMC) is unknown. The objective of this study was to determine whether cyclic strain stimulates the dephosphorylation of MLC20 in serum-fed SMC displaying a high basal level of phosphorylation. Confluent bovine aortic SMC were subjected to 10% average strain at 60 cycles per minute for 30 and 60 minutes. Basal MLC20 phosphorylation (N = non,M = mono,D = di) of serum-fed SMC was as follows: N = 34%:M = 27%:D = 39%. After 60 min of cyclic strain, both mono and diphosphorylated MLC20 were decreased to 21 and 15% respectively. The strain-induced dephosphorylation of MLC20 was partially inhibited by the protein phosphatase 1/2A inhibitor, calyculin A (5 nM). However, phosphorylase a phosphatase activities in Triton soluble and insoluble fractions of SMC were unaffected by cyclic strain. The data suggest that cyclic strain causes dephosphorylation of MLC20 in SMC which may be partially due to activation of MLC20 phosphatase and/or inhibition of MLC20 phosphorylation. PMID- 7999115 TI - Hypotension to central endothelin-1: effect of glutamate receptor blockade. AB - Endothelin-1 (ET-1) produces hypotension via an action at glutamate-sensitive medullary cardiovascular sites. Here, we used excitatory amino acid (EAA) receptor antagonists to examine the possible role of an endogenous EAA in this neural action of central ET-1. ET-1 (3 pmol) applied to the IV ventricle of anesthetized, artificially ventilated rats elicited a sustained decrease in blood pressure (27 +/- 6%). Pretreatment with two EAA receptor antagonists, APV and CNQX (or MK-801 and CNQX), significantly attenuated the hypotension to central ET 1 (11 +/- 4%). Since these antagonists do not interact with endothelin receptors, we conclude that release of an endogenous EAA may contribute to the hypotensive action of central ET-1. PMID- 7999116 TI - An additional role of transcriptional activation of ori lambda in the regulation of lambda plasmid replication in Escherichia coli. AB - Initiation of replication of plasmids derived from coliphage lambda in vivo is dependent on transcription at or near the replication origin, ori lambda. However, this transcriptional activation is dispensable for lambda plasmid DNA replication reconstituted in vitro from purified lambda and Escherichia coli proteins. It was proposed previously that histone-like protein HU interferes with the assembly or function of the pre-primosomal complex, and transcription at or near ori lambda abolishes HU-mediated inhibition of lambda DNA replication. We found that during lambda plasmid replication driven by the previously assembled replication complex (in amino acid-starved relA mutants), when the inhibition by HU protein should not be observed, the synthesis of lambda DNA was still dependent on transcriptional activation. Moreover, in hupA hupB double mutants the transcription is necessary for the initiation of lambda plasmid DNA replication perpetuated by the replication complex inherited by one of two daughter copies after a replication round. We conclude that transcriptional activation of ori lambda has an additional role in the initiation of lambda plasmid DNA replication beside the abolition of HU-mediated inhibition. PMID- 7999117 TI - Protein phosphatase inhibitors enhance the expression of an alpha-amylase gene, alpha Amy3, in cultured rice cells. AB - A rice (Oryza sativa L.) gene for alpha-amylase, alpha Amy3, was strongly and rapidly induced by treatment of suspension-cultured cells with okadaic acid (OA), a potent and specific inhibitor of protein serine/threonine phosphatases 1 and 2A. The massive accumulation of alpha Amy3 mRNA in response to OA treatment was due to the stimulation of gene transcription and a partial stabilization of this mRNA. This induction of alpha Amy3 message by OA occurred even though cellular protein synthesis was inhibited. Simultaneous treatment of cultured cells with OA and anisomycin synergistically induced alpha Amy3 expression. In addition, the inhibition of protein synthesis stabilized OA-induced alpha Amy3 mRNA. In the presence of protein kinase inhibitors H7, W7, and H8, alpha Amy3 mRNA accumulation induced by OA was unaffected. These results indicate that OA dependent alpha Amy3 induction is regulated transcriptionally by a signal transduction pathway involving protein phosphorylation, but independent of both protein kinase C and Ca2+/calmodulin- or Ca(2+)-dependent protein kinases. Furthermore, an AMP-activated protein kinase may be required for this induction of alpha Amy3 expression. PMID- 7999118 TI - Molecular cloning of rat RAC protein kinase alpha and beta and their association with protein kinase C zeta. AB - cDNAs of RAC protein kinases (RAC-PK) alpha and beta were cloned from a rat testis cDNA library. The predicted open reading frames encode 480 and 481 amino acids of RAC-PK alpha and beta, respectively, and the rat RAC-PK alpha and beta have sequences conserved among different mammalian species such as the pleckstrin homology domain at their amino-terminal region and the protein-serine/threonine kinase catalytic domain at their carboxyl-terminal region. RNA blot analysis showed wide distribution of two RAC-PK in rat tissues. Immunoprecipitation analysis revealed that RAC-PK alpha and beta associate with protein kinase C zeta through the pleckstrin homology domain in vitro, suggesting the interaction between RAC-PK and protein kinase C. PMID- 7999119 TI - Lectin conjugate-directed gene transfer to airway epithelial cells. AB - Many cell surface receptors contain covalently linked carbohydrates recognizable by lectins. This study examined the feasibility of using lectins as gene delivery vectors. Polylysine (PL) and histone (His) conjugates of concanavalin A (Con A), Maackia amurensis agglutinin (MAA), Sambucus nigra agglutinin (SNA), and wheat germ agglutinin (WGA), were employed to deliver pCMVlacZ to human airway epithelial cells (CFT1). As compared to the control (= 1.0), the beta galactosidase activities expressed in CFT1 cells transfected with lectin-PL/His DNA containing 5 micrograms/ml conjugate and 10 micrograms/ml DNA were: Con A His, 7.7; SNA-His, 3.5; Con A-PL, 2.4; WGA-PL/His, 1.3; others, 1.0. The efficiency of gene transfer directed by Con A-His was dose dependent between 2.5 and 10 micrograms/ml of the conjugate. The maximal beta-galactosidase activity expressed relative to the control was 42 obtained using 10 micrograms/ml conjugate. These results demonstrate that lectin-PL/His conjugates can be used as vectors to transfer genes to airway epithelial cells. PMID- 7999120 TI - Biochemical evidence for the long-tail form (A beta 1-42/43) of amyloid beta protein as a seed molecule in cerebral deposits of Alzheimer's disease. AB - We measured the amounts of total A beta, A beta 1-40 and A beta 1-42/43 in brain tissues using a newly developed ELISA assay and found that the amounts of insoluble A beta 1-42/43 and insoluble A beta 1-40 were linearly related to the amount of A beta deposits or total insoluble A beta at their lower and higher concentrations, respectively. In an experiment to characterize the A beta species in brain homogenates with buffered saline, we unexpectedly detected soluble A beta which was derived from the insoluble amyloid deposits in brain tissue, indicating reversible depolymerization of A beta from insoluble amyloid deposits. To confirm this finding, we performed 5 consecutive washes of insoluble precipitates of AD brains with buffered saline. Both species of A beta were found in all 5 supernatant fractions and their amounts were gradually decreased. The ratio of A beta 1-42/43 to A beta 1-40 was increased with the numbers of washes, indicating that A beta 1-40 existed in an exposed manner as compared to A beta 1 42/43. Thus the present finding is the first biochemical evidence that A beta 1 40 was the predominant species involved in the reversible exchanging reaction on seeding A beta 1-42/43 between the soluble and the insoluble forms (amyloid fibrils). PMID- 7999121 TI - Inactivation of phospholipase A2 by naturally occurring biflavonoid, ochnaflavone. AB - Ochnaflavone, a medicinal herb product isolated from Lonicera japonica, strongly inhibited rat platelet phospholipase A2 (IC50, about 3 microM). Inactivation was concentration and pH dependent (maximum inactivation occurred between pH 9.0 and 10.0). Ochnaflavone inhibited the enzyme by a noncompetitive manner, with the apparent Ki value of 3 x 10(-5) M. Reversibility was studied directly by dialysis method; the inhibition was irreversible. In addition, the inhibitory activity of ochnaflavone is rather specific against group II phospholipase A2 than group I phospholipase A2 (IC50, about 20 microM). Addition of excess Ca2+ concentration up to 8 mM did not antagonize the inhibitory activity of ochnaflavone. These results indicate that the inhibition of phospholipase A2 by ochnaflavone may result from direct interaction with the enzyme. PMID- 7999122 TI - The high density lipoprotein- and apolipoprotein A-I-induced mobilization of cellular cholesterol is impaired in fibroblasts from Tangier disease subjects. AB - Tangier disease (also known as familial HDL-deficiency) is characterized by very low high density lipoprotein (HDL) plasma levels, splenomegaly, and massive cholesteryl ester accumulation in the cytoplasm of various cell types. Since this phenotype may in part be caused by a defect in the pathway mediating cholesterol efflux from peripheral cells, we investigated the HDL3-mediated mobilization of cholesterol synthesized de novo from [14C]-mevalonolactone in cultivated fibroblasts from two patients with Tangier disease. Our results indicate that the HDL3-induced translocation of [14C]-cholesterol from intracellular pools to the plasma membrane and its subsequent secretion into the extracellular medium was approximately 50% less in the cells from the patients than in controls. The same result was also obtained with artificial apolipoprotein A-I-containing phospholipid vesicles. By contrast, no significant difference in HDL3-induced cholesterol efflux was observed when plasma membrane was labeled with exogenous [14C]-cholesterol. We conclude that inefficient cholesterol efflux in Tangier disease is primarily caused by impaired HDL3-induced activation of cholesterol translocation from intracellular pools to the plasma membrane. PMID- 7999124 TI - Role of the ribozyme of hepatitis delta virus on the transcription after polyadenylation. AB - We have previously demonstrated that the ribozyme located 34 nucleotides downstream of the polyadenylation site on the antigenomic RNA of the hepatitis delta virus can stabilize the downstream transcript after polyadenylation. Here, we have reports on further investigations of the molecular mechanism of this stabilization effect and the potential role of the small and large delta antigens. We found that the downstream transcripts after polyadenylation were stabilized by the ribozyme independently of either the small or large delta antigen. The stabilization effect was abolished as the ribozyme activity was eliminated by mutations on either the enzyme domain or target site of the ribozyme. These findings suggested that it was the ribozyme activity rather than the RNA structure or the delta antigens that contributed to the stabilization effect. PMID- 7999123 TI - Epidermal growth factor triggers the translocation of insulin-responsive glucose transporter (GLUT4). AB - In a novel cell line we developed for direct, sensitive detection of insulin responsive glucose transporter (GLUT4) on the cell surface, we considered that insulin-activated phosphatidylinositol 3-kinase (PI 3-kinase) may be involved in the signaling pathway of insulin-stimulated GLUT4 translocation. We report here evidence that epidermal growth factor (EGF), which stimulates PI 3-kinase activity, also triggers GLUT4 translocation in Chinese hamster ovary (CHO) cells stably overexpressing the EGF receptor. The EGF-dependent GLUT4 translocation is possibly mediated by two independent pathways: one by PI 3-kinase and the other by protein kinase C (PKC); the PI 3-kinase-mediated pathway predominates. Triggering of the GLUT4 translocation is not specific for insulin, rather it may be a common property of growth factors which activate PI 3-kinase. PMID- 7999125 TI - Effect of cysteine substitutions on the mitogenic activity and stability of recombinant human keratinocyte growth factor. AB - Human Keratinocyte growth factor (hKGF), a member of the FGF family of growth factors, contains five cysteines at amino acid positions 1, 15, 40, 102, and 106. We expressed five cysteine mutants of hKGF in which the cysteines were cumulatively replaced with alanine or serine, starting with cysteine-1. Recombinant hKGF has an inherently higher mitogenic activity and stability to heat and acid than reported for glycosylated hKGF. Mitogenic activity is increased an additional 2.6 fold by substitution of cysteine-1 with alanine. Mutants with the conserved cysteine substituted at position 40 were more susceptible to heat inactivation than rhKGF, but showed no significant difference in acid inactivation. Cysteine-free rhKGF is mitogenic, demonstrating that neither cysteines nor disulfide bonds are required for mitogenic activity. However, cysteine-free rhKGF does not bind Heparin-Sepharose and is unstable to heat and acid compared to rhKGF, suggesting that the cysteines have a role in maintaining KGF's structure. This information will useful in the development of a more stable and more potent wound healing agent from hKGF. PMID- 7999126 TI - Variations in ATP-sensitive K+ channel activity provide evidence for inherent metabolic oscillations in pancreatic beta-cells. AB - The cell-attached configuration of the patch clamp technique was used for studying slow variations in the activity of the ATP-sensitive K+ channels in pancreatic beta-cells isolated from mouse and man. In 0 or 3 mM glucose, the fraction of time the channels were open exhibited oscillations with frequencies in the 0.25-0.40/min range. This phenomenon is a strong argument for inherent fluctuations in the ATP production of the beta-cells. Variations in metabolism may thus be a major determinant for the characteristic large amplitude oscillations of cytoplasmic Ca2+ with equivalent frequency. PMID- 7999127 TI - Multiple transcription start sites and 5' alternate splicing of murine IL-3 receptor beta-chain transcripts. AB - The murine interleukin-3 receptor beta-chain genes, IL-3R beta IL-3 and IL-3R beta c, encode the signal transducing chains of the high affinity receptors for IL-3 and IL-3, GM-CSF and IL-5 respectively. Little is known about the regulation of their expression. To enable the study of the promotors of IL-3R beta IL-3 and IL-3R beta c, we have characterized their respective 5' untranslated regions using a modified 5' RACE protocol. Four classes of alternatively spliced transcripts were isolated that initiate in a 400 nt region upstream from a previously reported start site(1). The initially reported partial IL-3R beta IL-3 clone belongs to the first class of transcripts(2). The second class starts in the middle of an intron as defined by the first class. The 3rd and 4th class establish 2 novel splice donor sites. These results were confirmed by RNAse protection assay. The complex organization as evident from our data establishes an experimental framework for future experiments aimed at the study of the promoters for the murine IL-3R beta genes. PMID- 7999128 TI - Differential reactivity of two types of N-glycolyneuraminic acid dimers toward enzymatic and nonenzymatic hydrolysis of their interketosidic linkages. AB - The kinetics of acid- and sialidase-catalyzed hydrolysis of the interketosidic linkages of two different disialic acids, Neu5Gc alpha 2-->5-OglycolylNeu5Gc and Neu5Gc alpha 2-->8Neu5Gc, were studied. The former sequence was recently identified in the polysialic acid chains of a sialic acid-rich glycoprotein isolated from the egg jelly coat of two different species of sea urchins, and the latter was previously found in the cortical alveolar-derived polysialoglycoprotein from rainbow trout eggs. At pH values < 3.8, the rate of hydrolysis of Neu5Gc alpha 2-->5-OglycolylNeu5Gc was greater than that of Neu5Gc alpha 2-->8Neu5Gc. Paradoxically, however, Neu5Gc alpha 2-->5-OglycolylNeu5Gc was more stable than Neu5Gc alpha 2-->8Neu5Gc at pH values > 3.8. These findings indicate a greater contribution of intramolecular general acid catalysis to the lability of the alpha 2-->5-ketosidic linkage. Neu5Gc alpha 2-->5-OglycolylNeu5Gc was a poor substrate for Arthrobacter ureafaciens, Clostridium perfringens, and Vibrio cholerae sialidases, in contrast to Neu5Gc alpha 2-->8Neu5Gc. Neu5Gc alpha 2-->5-OglycolylNeu5Gc was essentially resistant to hydrolysis by A. ureafaciens sialidase. PMID- 7999129 TI - Histidyl phosphorylation of P36 in rat hepatoma Fao cells in vitro and in vivo. AB - We have previously shown that a membrane-associated P36 from rat liver was in vitro phosphorylated at His residue(s) with a phosphoric amide bond (FEBS Lett., 319:75-79, 1993), and the activity was solubilized and partially purified (J. Biol. Chem., 269:9030-9037, 1994). The present study demonstrates that the P36 histidyl phosphorylation occurs in rat hepatoma cells under normal conditions. Phosphorylation and dephosphorylation of histidine as well as those of serine, threonine and tyrosine residues may also play an important role in animal cells. PMID- 7999130 TI - Ammonia-forming cytochrome c nitrite reductase from Sulfurospirillum deleyianum is a tetraheme protein: new aspects of the molecular composition and spectroscopic properties. AB - Ammonia-forming cytochrome c nitrite reductase from Sulfurospirillum deleyianum contains four covalently bound heme c groups/55 kDa subunit as determined by atomic absorption spectroscopy and the pyridine Fe(II)-hemochrome technique. Nitrite reductase was isolated from the membrane fraction as a monomer (M(r) 55 +/- 2 kDa) and as a heterooligomeric complex. Both the monomeric and the complex form of the enzyme exhibited a high specific activity, with up to 1050 mumol NO2 min-1 mg-1. The complex was built from four 55 kDa units and contained a 22 kDa c type cytochrome which was absent in the monomeric form. EPR spectra of the complex displayed a prominent feature at g 4.83 (baseline crossing). This resonance, which was not observed in the spectra of the monomeric nitrite reductase, was assigned to the 22 kDa c-type cytochrome subunit. Identical results were obtained for the enzyme from Wolinella succinogenes which had been reinvestigated for comparison. PMID- 7999131 TI - Molecular cloning of human cytosolic purine 5'-nucleotidase. AB - The cDNA of human cytosolic purine 5'-nucleotidase (EC 3.1.3.5), which is the supposed regulatory allosteric enzyme of purine nucleotide degradation, has been cloned from a human placenta cDNA library. The predicted open reading fram encodes a protein of 561 amino acids with a molecular mass of 64,966 Da. The deduced amino acid sequence exhibits 95% identity with the sequence of the B type subunit of chicken cytosolic purine 5'-nucleotidase. Northern blot analysis of human placenta poly(A) +RNA revealed a single band of 3.6 kilobases using the cloned cDNA. PMID- 7999132 TI - Effect of hydroxyurea on 2',3'-dideoxycytidine activation. AB - The effect of hydroxyurea (HU) on cell growth, cell cycle progression, and the intracellular accumulation of 2',3'-dideoxycytidine (ddC) and ddCTP formation was examined. Twenty-four-hour exposure of H9 cells (human lymphocytic cell line) to 500 microM HU significantly increased the cells in the G1 phase and inhibited cell growth to 33.3 +/- 10.6% of control. The total intracellular ddC and ddCTP accumulation in HU-treated cells increased to 232.3% and 310% of control, respectively. PMID- 7999134 TI - Several liver specific DNAse hypersensitive sites are present in the intergenic region separating human plasminogen and apoprotein(A) genes. AB - The genes coding for plasminogen and apoprotein(a) are clustered, together with two related genes, on the telomeric region of chromosome 6 at band 6q26-27. Moreover, the two genes are 40 Kb apart and transcriptionally pointing to opposite directions. Plasminogen and apoprotein(a) share a high degree of homology in the promoter and 5' flanking regions and their expression is mainly confined to liver. To assess whether common controlling elements mediate the tissue specific expression of these two genes, the region between them was investigated for DNase hypersensitive sites in hepatic cell nuclei. PMID- 7999133 TI - Inhibition of G1 cyclin expression and G1 cyclin-dependent protein kinases by cAMP in an astrocytic cell line. AB - The effects of cAMP on cell cycle progression were examined using an astrocytic cell line. We show that forskolin and 8-bromo-cAMP block the basic Fibroblast Growth Factor-induced DNA synthesis, do not inhibit mitogen activated protein kinase activation whereas they reduce G1 cyclin (E and D1) expression without modification of cyclin A level. Furthermore, they inhibit the activation of cyclin A- and cyclin E-dependent histone H1 kinases. These results suggest that cAMP may exert its antiproliferative effects through the regulation of cyclin synthesis and cyclin-dependent kinase activation. PMID- 7999135 TI - Alzheimer amyloid protein precursor enhances proliferation of neural stem cells from fetal rat brain. AB - We have investigated the effect of the Alzheimer amyloid protein precursor (APP) on the proliferation of neural stem cells. Two secretory forms of APP (sAPP770 and sAPP695, with and without the Kunitz-type serine protease inhibitor domain, respectively) were purified from conditioned media of COS-7 cells transfected with genetically modified APP cDNAs. Both secretory APPs promoted the growth of neural stem cells, and the effect of sAPP770 was greater than that of sAPP695. sAPP770 and known growth factors in combination exerted a cooperative stimulation of the stem cell proliferation. These results suggest that APP, especially APP possessing the protease inhibitor domain, regulates the growth of neuronal precursor cells during development of the nervous system. PMID- 7999136 TI - Chimerism in PCR products from a multigene family. AB - This paper describes a potential hazard in obtaining sequences of a multigene family by amplifying the mixed population by the polymerase chain reaction with primers from conserved sequences. We describe a product which appears to be a chimera formed during the PCR reaction from two different but related sequences. PMID- 7999137 TI - Antimicrobial peptides from the skin of a Korean frog, Rana rugosa. AB - Six antimicrobial peptides, named gaegurins, were isolated from the skin of a Korean frog, Rana rugosa, and their amino acid sequences were determined by automated Edman degradation. All peptides contain two invariant cysteine residues, one at their C-terminus and the second at the seventh position from the C-terminus. The heptapeptides containing these two cysteine residues, which we designate 'Rana boxes', are conserved in the antimicrobial peptides derived from other Rana species. Each peptide manifested a broad spectrum of antimicrobial activity against Gram positive and Gram negative bacteria, fungi and protozoa with slightly different specific activities. All gaegurins manifest very little or no hemolytic activity. These properties provide the potential for application of these peptides to effective therapeutic agents for control of pathogenic microorganisms. PMID- 7999138 TI - Utilization of geranylgeraniol for protein isoprenylation in C6 glial cells. AB - When rat C6 glial cells were incubated with [3H]geranylgeraniol (GGol), radioactivity was incorporated into a delipidated protein fraction. SDS-PAGE analysis of the protein fraction labeled by [3H]GGol revealed a 46 kDa polypeptide and a group of labeled polypeptides (19-27 kDa) in the same size range as the small GTP-binding proteins. A similar pattern of labeled polypeptides was seen when C6 cells were metabolically labeled with [14C]mevalonolactone. An isotopically labeled product, chromatographically identical to geranylgeranylcysteine (GG-Cys), was released by Pronase E digestion of the [3H]GGol-labeled protein. When the protein fraction from cells metabolically labeled with [3H]mevalonolactone was digested with Pronase E, two radiolabeled products were released with the chromatographic mobilities of farnesyl-cysteine (F-Cys) and GG-Cys. These studies suggest that C6 glial cells are capable of converting GGol to geranylgeranyl pyrophosphate (GG-P-P), or perhaps a novel "activated" form of the allylic isoprenol, that can be utilized for protein isoprenylation reactions. PMID- 7999139 TI - Appearance of high enzyme activity in immobilized urease disc by electron beam irradiation technique. AB - A new preparation method of immobilized urease discs for biomedical applications, which was a thin circular film (200 microns, 50mm phi), was developed. The method was achieved by electron beam irradiation of polyethyleneglycol diacrylate monomers in the addition of paper disc and bean powder as protective substance for irradiation by which a denaturation of the enzyme by irradiation was effectively prevented. The immobilized enzyme disc with a high enzyme activity (remaining activity yield), about 90%, was obtained. The enzyme activity was varied by the preparation conditions such as the thickness of paper disc, monomer concentration etc. The enzymes were trapped near the surface of the disc to be easily reacted with substrate. The trapped state of the enzymes appeared to be affected by a hydrophilicity of the polymers. PMID- 7999141 TI - NMR and molecular modelling based conformational analysis of some N-alkyl 1- and 2-benzazepinones: useful central nervous system agent design motifs. AB - Variable temperature 1H NMR lineshape analyses and 13C NMR spin-lattice relaxation time studies were undertaken to characterise the conformationally dynamic N-alkyl 1- and 2-benzazepinones 1 and 2. For 1, dynamic interchange between two mirror-image puckered forms of the azepine ring occurs with a barrier of 56 kJ mol-1. There is a significantly greater degree of ring flexibility in the case of 2. Molecular modelling studies were used to examine the degree of sidechain flexibility in these compounds. PMID- 7999140 TI - Thiamine disulfide as a potent inhibitor of human immunodeficiency virus (type-1) production. AB - Thiol and disulfide compounds were tested as an anti-HIV drug against transactivator (Tat)-mediated transactivation of HIV-1. Of all the compounds tested, thiamine disulfide, alpha-lipoic acid, and N-acetycysteine significantly depressed HIV-1 Tat activity. Thiamine disulfide alone in these compounds possessing anti-HIV-Tat activity markedly inhibited production of progeny HIV-1 in acute and chronic HIV-1-infected CEM at nontoxic concentrations of 500-1000 microM. Thiamine disulfide (500 microM) blocked 99.7% of HIV-1 production after 96 hr culture in acute HIV-1 (LAV-1) infection (m.o.i. = 0.002), whereas it inhibited 90-98% of HIV-1 production in chronic-infected cells (CEM/LAV-1, H9/MN, and Molt-4/IIIB). The results suggest that thiamine disulfide may be important for AIDS chemotherapy. PMID- 7999142 TI - The Saccharomyces cerevisiae gene product SDC25 C-domain functions as an oncoprotein in NIH3T3 cells. AB - Ras proteins in mammalian cells cycle between a GTP-bound 'on' state and a GDP bound 'off' state. Activation of Ras p21 results from the dissociation of tightly bound GDP and the exchange of bound GDP for GTP. A guanine nucleotide exchange factor is required for this activation. Activation promotes interaction with effector molecules and allows the signal to be transduced. In Saccharomyces cerevisiae, the function of guanine nucleotide exchange has been ascribed to the product of the CDC25 gene. The C-terminus domain of SDC25, a homologue of CDC25, can substitute for the CDC25 protein in yeast. We have demonstrated that the SDC25 C-terminus domain promotes GTP binding to Ras p21 in CHO cells. In the present study, we found that the stable expression of the SDC25 C-terminus domain induced transformation of NIH3T3 cells. Ras proteins in these tumorigenic cells were GTP bound. In addition, the coexpression of wild-type Ha-Ras protein with the SDC25 C-terminus was found to enhance the tumorigenic properties of the NIH3T3 cells. These results imply that, in subsets of human tumours, cellular Ras p21 might be found in its GTP-bound active form as a consequence of an oncogenic activation of a mammalian Ras guanine nucleotide exchange factor. PMID- 7999143 TI - Cloning and sequence analysis of the coat protein genes of an Australian strain of peanut mottle and an Indonesian 'blotch' strain of peanut stripe potyviruses. AB - We have analysed the coat protein gene sequences of two potyviruses infecting peanut. The 3' terminal 1247 nucleotides (nt) of an Australian strain of peanut mottle virus (PeMoV-AU) and the 3' terminal 1388 nt of an Indonesian 'blotch' strain of peanut stripe virus (PStV-Ib) were cloned and sequenced. Those regions included the 861 and 864 nt encoding the respective putative coat proteins as well as the 285 and 253 nt, respectively of 3' non-coding sequences. Comparison of the nucleotide sequences of PeMoV-AU and PStV-Ib revealed a sequence similarity of 64.4% for the coat protein gene and 34.6% for the 3' non-coding region. The deduced amino acid sequences of PeMoV-AU and PStV-Ib coat proteins are 66.7% identical. These results provide further evidence that PeMoV and PStV are distinct viruses. Comparisons of the 3' terminal sequences of PeMoV-AU and PStV-Ib with those of the genomic RNA of other strains of PeMoV and PStV and with other potyviruses are discussed. PMID- 7999144 TI - Identification of an invasion-inducing gene, Tiam-1, that encodes a protein with homology to GDP-GTP exchangers for Rho-like proteins. AB - Using proviral tagging in combination with in vitro selection for invasiveness, we have identified a gene, designated Tiam-1, that affects invasion. In the selected invasive T lymphoma variants, proviral insertions were found within coding exons of the Tiam-1 gene, resulting in both truncated 5'-end and 3'-end transcripts that give rise to N- and C-terminal Tiam-1 protein fragments. In one invasive variant, amplification of the Tiam-1 locus was observed with concomitant increase in the amount of normal Tiam-1 protein. Cell clones that were invasive in vitro produced experimental metastases in nude mice, and transfection of truncated Tiam-1 cDNAs into noninvasive cells made these cells invasive. The predicted Tiam-1 protein harbors a Dbl- and Pleckstrin-homologous domain, which it shares with GDP-GTP exchangers for Rho-like proteins that have been implicated in cytoskeletal organization. PMID- 7999146 TI - Case records of the Massachusetts General Hospital. Weekly clinicopathological exercises. CASE 28-1994. A 51-year-old man with a nonhealing finger wound and regional lymphadenopathy. PMID- 7999145 TI - Characterization of murine lung inflammation after infection with parental Bordetella pertussis and mutants deficient in adhesins or toxins. AB - Bordetella pertussis expresses factors such as filamentous hemagglutinin, agglutinogens, pertactin, and pertussis toxin, which participate in bacterial adhesion; pertussis toxin, dermonecrotic toxin, lipopolysaccharide, and tracheal cytotoxin, which are responsible for toxic effects; and adenylate cyclase hemolysin, which is required to initiate infection. By using a murine respiratory model, we showed that the RGD sequences of filamentous hemagglutinin and pertactin are important for bacterial persistence. However, mutants deficient in filamentous hemagglutinin and agglutinogens or in pertactin and the RGD sequence of filamentous hemagglutinin behaved as did wild-type B. pertussis, i.e., induced bronchopneumonia, alveolitis, and an influx of macrophages, lymphocytes, and polymorphonuclear leukocytes into bronchoalveolar lavage fluids. These results suggest that these adhesins are not involved in the induction of pulmonary lesions following infection. The intensity of inflammation was markedly reduced after infection with mutants deficient in either hemolytic activity or pertussis toxin expression, whereas a mutant devoid of adenylate cyclase activity behaved as did the avirulent mutant. Pertussis toxin and adenylate cyclase-hemolysin may act indirectly by altering immune cell functions and thus allowing other factors, such as filamentous hemagglutinin, agglutinogens, and pertactin, to trigger adhesion and lipopolysaccharide, dermonecrotic toxin, and tracheal cytotoxin to induce their toxic effects. However, it is possible that pertussis toxin is also responsible for the induction of some pulmonary alterations. PMID- 7999147 TI - Projections from nucleus raphe obscurus to the periaqueductal grey matter in the rat. AB - Retrograde transport of rhodamine- or coumarin-labelled latex microspheres was used to investigate projections from nucleus raphe obscurus (NRO) to the periaqueductal grey matter (PAG) in rats. Few labelled neurones (3.5 +/- 1.2; mean +/- S.E.M.) were seen in NRO after injections of microspheres into the dorsolateral and lateral PAG (n = 11) but after injections into the ventrolateral sector (n = 9), significant numbers (42.6 +/- 8.1) were present, particularly in the rostral third of NRO (66% of labelled cells). The results suggest that the projection from NRO to the PAG is restricted to the ventrolateral sector. Any influence of NRO on the dorsal PAG must therefore be mediated indirectly. PMID- 7999148 TI - Growth patterns of infants exposed to cocaine and other drugs in utero. AB - OBJECTIVE: Exposure to cocaine in utero is known to cause intrauterine growth retardation. This study describes the postnatal growth patterns of infants exposed to cocaine and other drugs in utero. DESIGN: A convenience sample of 31 Northern California infants was monitored for 1 year. Infants in foster care were selected to eliminate the environmental effects of a parent's drug-seeking lifestyle. Entrance criteria consisted of age less than 6 months old, in utero drug exposure, and foster-care placement shortly after birth. The infants were predominantly black. ANALYSIS: The infants' growth indexes were compared with the expected growth of infants in three reference populations: the National Center for Health Statistics (NCHS) reference population, all infants in the 1991 Pediatric Nutrition Surveillance System (PNSS-all), and black infants in the 1991 PNSS (PNSS-black) using the one-sample exact binomial test. Infants took in more energy and protein per kilogram than 100% of the Recommended Dietary Allowances at every age interval. RESULTS: At birth, mean weight of the study infants was significantly lower than that of NCHS, PNSS-all, and PNSS-black infants (P < .01); mean length was significantly lower than that of NCHS and PNSS-all infants (P < .01), but not significantly different from PNSS-black infants. By 6 months, there were no significant differences in weight compared with any group. At all age intervals after birth, mean length for the study infants was significantly less than that of NCHS and PNSS-all infants (P < .01), and significantly less than that of PNSS-black infants (P < .05). Our findings indicate that despite adequate nourishment, stunting in length continued through the first year, resulting in infants who were overweight for length. PMID- 7999149 TI - Immune-based interventions in perinatal human immunodeficiency virus infection. AB - Essentially all new cases of human immunodeficiency virus (HIV) infection in infants and young children occur as a consequence of exposure to HIV either in utero, intrapartum or postpartum during breast feeding. Currently it is estimated that the majority of vertical transmission of HIV occurs at or near the time of birth. Based on what is known about the biology of perinatal HIV transmission, the HIV burden of the mother, effectiveness of her immune response and that of her fetus/infant and the integrity of the placental "barrier" are likely to play important roles in this process. The role of impaired immunologic control of HIV is gaining recognition as a potential key element in the pathophysiology of perinatal HIV transmission. In most studies to date, advanced maternal disease and low CD4 lymphocyte count have been associated with increased risk of vertical HIV transmission. In addition some studies have indicated that low maternal titers of antibodies to certain V3 loop epitopes may have a similar effect on vertical transmission. Cellular immune responses, which are known to play an important role in host defense against HIV, appear to be impaired in infants after exposure to HIV, especially those responses involving the development of cytotoxic lymphocytes. Mounting evidence suggests that enhancement of humoral and/or cellular immune responses in pregnant women and exposed infants is a logical and potentially feasible approach to interruption of perinatal transmission (an approach similar to that utilized for perinatally acquired hepatitis B virus infection). Studies are now in progress to assess HIV hyperimmune globulin and envelope HIV vaccines in pregnant woman and HIV-exposed infants. PMID- 7999150 TI - [Iodine prophylaxis during pregnancy]. PMID- 7999151 TI - Arachidonic acid and peanut oil. PMID- 7999153 TI - Small cardioactive peptide B increases the responsiveness of the neural system underlying prey capture reactions in the pteropod mollusc, Clione limacina. AB - Effects of small cardioactive peptide B (SCPB) on cerebral neurons which underlie prey capture in the carnivorous pteropod mollusc, Clione limacina, were investigated. SCPB in concentrations of 10 microM and higher produced direct activation of cerebral ganglion neurons underlying extrusion of buccal cones used in prey capture. SCPB in lower concentrations, between 1 and 5 microM, did not have a noticeable effect on the membrane potentials of these neurons; however, it significantly increased their responsiveness to sensory inputs from the tactile stimulation of the head, and their ability to generate afterdischarge activity. SCPB immunoreactivity was observed in cell bodies in buccal, cerebral, pedal, and intestinal ganglia, as well as in the anterior esophagus and in buccal cones where fibers stained intensely. These electrophysiological and immunohistochemical data suggest that SCPB may have a physiological role in feeding arousal in Clione. PMID- 7999154 TI - Invited letter concerning: double lung transplantation in situs inversus with Kartagener's syndrome. PMID- 7999152 TI - Specific binding of dehydroepiandrosterone sulfate to rat liver cytosol: a possible association with peroxisomal enzyme induction. AB - Incubation of [3H]dehydroepiandrosterone sulfate (DHEAS) with rat liver cytosol demonstrated its specific binding with a dissociation constant of 72 +/- 14 nM and a maximal binding capacity of 312 +/- 105 fmol/mg cytosol protein. The binding correlated with the amount of cytosol protein, and depended on time, temperature and pH, with equilibrium being reached after 6 h at 0 degrees C and pH 7.5. Boiling or treatment of the cytosol with proteases or sulfhydryl-blocking reagents affected the binding. The apparent molecular mass of the binding entity was estimated to be 160-230 kDa by HPLC gel filtration. In competitive binding studies, free steroids, including dehydroepiandrosterone (DHEA), sulfatase substrates and ligands of organic anion binders such as ligandin and fatty acid binding protein, had no effect on the [3H]DHEAS binding. Peroxisome proliferators also had no effect, except Wy-14,643. Competition with various steroids related to DHEAS revealed strict structural requirements for DHEAS binding, in which epiandrosterone sulfate was almost as effective as unlabeled DHEAS in inhibiting [3H]DHEAS binding. These findings indicated the presence of a binding protein highly specific to DHEAS in rat liver cytosol. The DHEAS binding in liver cytosol was 2-fold higher in male than in female rats. The cytosolic DHEAS binding was highest in the liver, followed by the kidney and heart. The possibility of association between the DHEAS binding and DHEA induction of peroxisomal beta oxidation is discussed. PMID- 7999155 TI - A conceptual framework for outcomes research in arthroscopic meniscectomy: results of a nominal group process. AB - Standard measures for the assessment of arthroscopic knee surgery are needed, as existing instruments do not cover the full range of relevant outcomes. Using a modified nominal group technique, a panel of orthopedic surgeons and methodologists developed a conceptual framework for the assessment of arthroscopic knee procedures. The outcome domains included in the evaluation comprised traditional measures such as range of motion, complications, and other objective parameters, as well as patient-centered variables such as health status and satisfaction. Independent variables that might influence the outcome of surgery included traditional measures such as knee alignment as well as comorbidity and patient expectations. This conceptual framework should allow a more comprehensive, patient-centered assessment of the outcome of arthroscopic meniscectomy. PMID- 7999156 TI - Outcomes research in orthopedics: history, perspectives, concepts, and future. PMID- 7999158 TI - Arthroscopic capsular advancement for anterior and anterior-inferior shoulder instability: a preliminary report. AB - The arthroscopic treatment of anterior and anterior-inferior shoulder instability has been limited by the surgeon's ability to adequately advance the glenohumeral ligament complex medially and superiorly. We describe a modification of the arthroscopic Bankart repair that includes an inferior capsular split. This technique allows up to 2 cm of additional capsular advancement, thus providing greater reduction of the stretched or redundant capsule if necessary. The short term results in four cases are presented. PMID- 7999157 TI - Anterior cruciate ligament reconstruction: endoscopic versus two-incision technique. AB - The purpose of this study was to compare the single-incision, "endoscopic" (ENDO) anterior cruciate ligament (ACL) reconstruction technique with the two-incision, "rear-entry" technique (RE). Sixty patients were entered into a prospective study. Thirty patients underwent ACL reconstruction by the RE technique, followed by 30 consecutive patients using the ENDO procedure. Postoperatively all patients followed a standardized rehabilitation protocol. Follow-up evaluation consisted of a detailed physical examination, range of motion, thigh girth, vertical leap, hop test, KT-1000 testing, and patient interview. They were scored according to the International Knee Documentation Committee (IKDC) protocol, which takes objective and subjective data into account. Patients were also assessed for level of sports activity including frequency and type. Finally, anteroposterior and lateral x-ray films were evaluated with a scoring system for tunnel location. Of the initial 60 patients entered into the study, 50 were available for a detailed clinical and functional review (83%). Demographic comparisons revealed 24 RE patients and 26 ENDO patients. There were 16 men and 8 women in the RE group. The ENDO group comprised 16 men and 10 women. There were 14 right knees and 10 left knees in the RE group. In the ENDO group there were 13 right knees and 13 left knees. The average age in the RE group was 24 years and 25 years in the ENDO group. The average follow-up was 35 months (range 31-40 months) in the RE group and 29 months (range 24-35 months) in the ENDO group. Complications included two patients with loss of motion in the RE group and three in the ENDO group. There were no significant differences between the two groups tested with respect to the overall IKDC rating scale. Anteroposterior and lateral x-ray films revealed no significant differences in femoral and tibial tunnel placement. In conclusion, no significant functional or radiographic differences at a minimum 2-year follow-up could be identified when comparing the two ACL reconstructive techniques. PMID- 7999159 TI - Arthroscopic subacromial decompression in the treatment of full thickness rotator cuff tears: a 3- to 6-year follow-up. AB - Arthroscopic subacromial decompression has become an accepted treatment for patients with impingement syndrome; however, its use for full thickness rotator cuff tears continues to be controversial. The purpose of this study is to determine if the results of arthroscopic subacromial decompression alone for full thickness rotator cuff tears deteriorate at long-term follow-up. We reevaluated all 25 patients with full thickness rotator cuff tears who underwent arthroscopic subacromial decompression from our original study group. Based on the University of California at Los Angeles shoulder rating, 68% of patients were rated as excellent or good at the present mean follow-up of 45.8 months (range 36-72 months). This represents a significant decrease from our initial report of 84% satisfactory results at a mean follow-up of 24.6 months. There was a significant decrease in ratings with regard to pain and function; however, no significant deterioration was noted with regard to motion and strength. Two additional patients required open rotator cuff repair since the time of initial follow-up for a total of six. Large and massive rotator cuff tears fared worse over time as compared with small and moderate size tears. Although 1- to 3-year results of arthroscopic subacromial decompression and rotator cuff debridement were favorable, the long-term follow-up demonstrates deterioration of results. We therefore cannot support the use of decompression and debridement alone in the treatment of repairable full thickness rotator cuff tears. PMID- 7999160 TI - Optimal graft fixation--the effect of gap size and screw size on bone plug fixation in ACL reconstruction. AB - In reconstruction of the anterior cruciate ligament (ACL), using central one third patellar tendon graft, an early weak link is the bone plug junction. To study this, we carried out experiments to determine the relationship between gap size, screw size, and pullout force of patellar bone plugs inserted in the femur of the porcine model. Forty-nine porcine knees were obtained. Holes 11 mm in diameter were drilled in the intercondylar notch of the femur. Bone plugs fashioned from the patella were made to fit the holes with gap sizes of 1, 2, 3, or 4 mm. The bone plugs were inserted into the holes in the femur and secured by means of 20-mm-long screws (either 7- or 9-mm diameter). The bone plugs were then pulled out using a tensile testing machine and the pullout force was measured. The results suggest that a 7-mm (or a 9-mm) diameter screw can be used for gaps of 1 and 2 mm, and a 9-mm diameter screw should be used for gaps of 3 and 4 mm. PMID- 7999161 TI - The effect of cold therapy on pain, swelling, and range of motion after anterior cruciate ligament reconstructive surgery. AB - This prospective study assessed the effect of cold therapy on pain, pain medication use, limb swelling, and knee range of motion in 131 patients who had an arthroscopically assisted anterior cruciate ligament reconstruction. Patients were randomized into five treatment groups. Cooling pads were incorporated into the dressing in 89 patients, and no cooling pads were used in 42 patients. There were four cooling-pad temperature groups: 40 degrees F, 45 degrees F, 55 degrees F, and 70 degrees F. The cooling pads lowered the skin temperature. There was no difference between groups with respect to hospital stay, pain medication use, pain scale, knee girth, or range of motion. PMID- 7999162 TI - Office operative arthroscopy of the knee: technical considerations and a preliminary analysis of the first 100 patients. AB - Office operative arthroscopy of the knee under local anesthesia with light intravenous sedation was performed on 106 knees in 100 patients between 1989 and 1992. There were 169 procedures performed in these 106 knees. Facility design and necessary equipment and supplies are presented. Patient flow in the office, from check in to check out after surgery, is discussed in detail. Anesthesia techniques, monitoring techniques, and emergency precautions are presented. Patients were asked to complete a questionnaire assessing their comfort level during and satisfaction with office arthroscopy during and following the procedure. Twenty-four patients had undergone previous arthroscopy under general anesthesia in a hospital or ambulatory surgery center setting. These patients were asked to compare their previous procedure with the office procedure as to discomfort and the overall experience. Only 1 of these 24 patients preferred the hospital setting to the office setting. The discomfort experienced during the procedure was almost universally rated as minimal. There were four minor complications, which are discussed in detail. The cost-effectiveness of office operative arthroscopy under local anesthesia with light intravenous sedation is demonstrated and discussed. This preliminary report demonstrates that office operative arthroscopy of the knee is feasible, cost-effective, safe, and preferred by the patient. PMID- 7999163 TI - The results of arthroscopic lateral release of the extensor mechanism for recurrent dislocation of the patella after 8 years. AB - We reviewed 41 knees at a mean of 4 years after arthroscopic lateral release of the extensor mechanism. The operations were performed for recurrent complete dislocation, not for subluxation, maltracking, or lateral pressure syndrome. Thirty-three of these knees were reviewed again 8 years after operation. There were 39% excellent results according to the criteria of Crosby and Insall at 4 years and 30% at 8 years. Patellar stability improved between 4 and 8 years (p < 0.01). The results in patients with subluxation of the patella on extension of the knee or generalized ligament laxity were poor; five of seven patients with these conditions were worse and had undergone another operation. With these conditions excluded, the excellent results decreased from 50% after 4 years to 37% after 8 years. The results of lateral release are better than those reported after other procedures. It is concluded that arthroscopic lateral release is the procedure of choice for patients with recurrent complete dislocation of the patella unless there is abnormal ligament laxity or subluxation on extension. The operation should not be performed in the presence of these conditions. PMID- 7999164 TI - Posterior cruciate ligament tibial attachment anatomy and radiographic landmarks for tibial tunnel placement in PCL reconstruction. AB - The posterior cruciate ligament (PCL) was dissected in 12 frozen human cadaver knees. The tibial attachment was radiographically mapped and guide wires placed on the distal-lateral bulk of the ligament's tibial attachment. Radiographic landmarks were then described on the anteroposterior and lateral radiographs to assist in tibial tunnel guide wire placement in PCL reconstruction. The radiographic site corresponding to the posterior ridge of the tibial plateau approximately 1 cm below the joint line and a few millimeters lateral to the center of the lateral tibial tubercle will reliably confirm tibial tunnels in PCL reconstruction. PMID- 7999166 TI - Magnetic resonance signals in healing menisci: an experimental study in dogs. AB - This study examined the magnetic resonance imaging (MRI) signal from healing menisci in adult dogs. Complete, full-thickness radial tears were created in the medial menisci of adult dogs and allowed to heal spontaneously. Menisci were harvested and examined at 8, 12, and 26 weeks after injury using a spin-echo imaging sequence. After imaging, the menisci were processed for routine histologic examination. The results of the study demonstrated that the repair tissue consistently yielded an increased MRI signal as compared with the normal meniscal tissue. This increased signal persisted at 26 weeks even though the repair tissue had modulated from fibrovascular scar tissue into fibrocartilage. The results of this study confirm the clinical impression that normal fibrovascular repair tissue in the healing meniscus can emit persistently increased signals on MRI examination. However, the long-term history of these signals remains unknown. PMID- 7999165 TI - Femoral notchplasty in the treatment of malunited intercondylar eminence fractures of the tibia. AB - A block of full extension may occur after malunion of an intercondylar tibial eminence fracture. Five patients with this complication were treated by arthroscopic femoral notchplasty. At follow-up, between 6 months and 5 years, four patients had regained full extension and the fifth was improved. This is an effective method of regaining extension in selected patients. PMID- 7999167 TI - Disruption of the ankle syndesmosis: biomechanical study of the ligamentous restraints. AB - We investigated the relative importance to stability of the four component ligaments of the distal tibiofibular syndesmosis. Eight fresh-frozen cadaver specimens were tested on a hydraulic test system during sequential cutting of the ligaments. The percentage resistance to 2 mm of diastasis was measured for the four ligaments. The anterior inferior tibiofibular ligament provided 35%, interosseous ligament 22%, superficial posterior inferior tibiofibular 9%, and deep posterior inferior tibiofibular 33%. These results have clinical implications with regard to injury. Damage to the syndesmosis should be assessed anteriorly and posteriorly at the time of examination. The interosseous ligament can be visualized arthroscopically. PMID- 7999168 TI - Disruption of the ankle syndesmosis: diagnosis and treatment by arthroscopic surgery. AB - Over a 10-year period, 19 patients were seen who had the clinical features of disruption of the syndesmotic ligaments of the ankle. Seventeen of these were available for follow-up by history and 13 by physical examination. The patients underwent an arthroscopy for persistent symptoms an average of 2 years following the injury. Preoperatively the patients had a positive external rotation stress test. A triad of pathological features was found: disruption of the posterior inferior tibiofibular ligament; rupture of the interosseous ligament; and chondral fracture of the posterolateral portion of the tibial plafond. Arthroscopic resection of the torn portion of the interosseous ligament and the chondral pathology successfully relieved the symptoms in most of the patients. There was a statistically significant improvement in pain, swelling, stiffness, stability, limp, and activity levels. The external rotation stress test was converted to negative. Patients with persistent pain following a syndesmotic disruption of the ankle can benefit substantially by removal of the intraarticular pathology associated with such injuries. Residual instability of the syndesmosis itself did not seem to be a problem. PMID- 7999169 TI - Management of complete traumatic anterior cruciate ligament tears in the skeletally immature patient: current concepts and review of the literature. AB - Once considered extremely rare, complete traumatic tears of the anterior cruciate ligament (ACL) in skeletally immature patients with open physes are now being diagnosed with increasing frequency. Concomitant subsequent meniscal injuries develop in a significant number of these patients. Nonoperative treatment, primary surgical repair of the torn ACL, or extraarticular stabilization procedures have not been reported to restore dynamic knee stability or prevent further meniscal damage. Transphyseal bone plugs from a patellar tendon graft fixed with suture or interference screws have not been reported in patients with significant growth potential and cannot be recommended. Soft-tissue autografts placed through transphyseal tunnels have been reported to give good functional results and minimize potential for growth disturbance. PMID- 7999170 TI - Ganglion cysts of the anterior cruciate ligament. AB - Ganglion cysts arising from the anterior cruciate ligament are rare, with very few reports available in the literature. We are reporting a case of a ganglion cyst in the anterior cruciate ligament found and treated at arthroscopy with our suggestions regarding its etiology. PMID- 7999171 TI - The specialist and health care reform: what's going on? PMID- 7999172 TI - Putting the scope on health system reform. PMID- 7999173 TI - Arthroscopic labral repair to the glenoid rim. PMID- 7999174 TI - A sublabral foramen must not be confused with a Bankart lesion. PMID- 7999175 TI - Intra-articular injection. PMID- 7999176 TI - On the connection between CME and education in medical schools. PMID- 7999177 TI - Improving medical residents' attitudes toward HIV-infected persons through training in an HIV staging and triage clinic. AB - PURPOSE: To assess the effect of a weekly outpatient clinic for staging and triage of newly identified human-immunodeficiency-virus (HIV)-infected patients on medical residents' attitudes and knowledge regarding care of HIV-infected persons. METHOD: Twenty-one second- and third-year medical residents who participated in the Diagnostic Evaluation Unit (DEU) of Boston City Hospital's Clinical AIDS Program from July 1991 through December 1991 were matched with a control group of 20 residents. Both groups of residents were asked to anonymously complete self-administered questionnaires before, immediately after, and three months following the DEU rotation. Responses were compared using repeated measures analysis of variance, two-tailed t-tests, and chi-square analysis. RESULTS: Compared with the controls, the DEU residents showed an increased sense of feeling adequately trained to provide primary care to HIV-infected patients immediately after the rotation (p = .0002), which was sustained at the three month follow-up (p < .001). Compared with the controls, the DEU residents also showed improved general attitudes toward treating persons with acquired immune deficiency syndrome, which persisted at the three-month follow-up, although these changes were not significant. CONCLUSION: The experience in an HIV staging and triage clinic had a positive effect on the confidence and attitudes of the medical residents. Similar training experiences may increase the willingness and capacity of physicians to provide primary care to HIV-infected persons. PMID- 7999178 TI - Obstetric patients who select and those who refuse medical students' participation in their care. AB - PURPOSE: To assess attitudes and expectations of obstetric patients toward the involvement of medical students in their care. METHOD: At the Medical Center Hospital of Vermont in 1991, questionnaire responses were collected from 222 obstetric patients who had been assisted by clerkship students from the University of Vermont College of Medicine and 78 patients who had refused the participation of students. The responses were analyzed for differences in demographic backgrounds, prior hospital experiences, and general expectations of student involvement, using chi-square, two-tailed t-tests and analysis of variance. RESULTS: Both groups of respondents consisted primarily of young, well educated, married women, who appear to have made their decisions about student participation by balancing their personal needs and their sense of altruism. For example, 61% of those who had refused the participation of students ranked the desire for privacy as their primary reason, whereas 73% of those who had accepted student participation ranked as their primary reason the desire to contribute to a student's education. Although both groups of patients expected the students to perform few clinical procedures, the patients who had refused student participation expected the students to be more involved in patient care than did the patients who had allowed participation. Of the 25% of the patients who had had students involved in prior pregnancy care, those who had currently refused student participation had less positive views of prior student care. CONCLUSION: Patients' needs for privacy, past experiences with student care, and expectations of student performance should be considered to ensure the respectful incorporation of student involvement in obstetric care. PMID- 7999180 TI - Financial management of academic clinical departments. AB - Based on their ten years of experience, the authors describe how they have organized and managed the financial resources in the department of medicine at the University of Maryland School of Medicine. They outline how to develop realistic budgets to best account for different sources of income and expenses and how to utilize subsidies and incentives to challenge division heads and faculty to administer their units efficiently and maximize income. The values of regular financial reports, of an annual retreat of the division heads, and of effective departmental administration to maintain financial stability and progress of are emphasized. Finally ,the authors explain why they favor a more open policy of sharing much of the department's financial information rather than restricting such data to leadership. PMID- 7999179 TI - Graduate medical education consortia: expectations and experiences. AB - Graduate medical education (GME) consortia are formal associations of medical schools, teaching hospitals, and other organizations involved in residency training, with central support, direction, and coordination allowing members to function collectively. GME consortia are not well documented in the literature, although they are included in many GME reform proposals. Proponents expect consortia to improve the organizational structure and governance of residency training programs and, through local coordination and possibly the allocation of resources, to help members meet national workforce goals regarding both numbers and practice locations for generalist and specialist physicians. The authors contrast the expectations of educators and policymakers for the future performance of GME consortia with the experiences of 36 functioning consortia, gathered in a 1993 national survey conducted by the Maine Medical Center and the Association of American Medical Colleges. Respondents account for nearly 10% of all residency training programs and 17% of all residents nationwide. The participating consortia differ markedly in their structures, functions, and other features, although nearly 85% have been convened by medical schools and closely affiliated hospitals. Fewer than half function with governing boards; 40% offer a single integrated residency training program in each discipline; and 58% allocate resources. A common concern of consortium members was physician distribution by specialty, but only 31% identified "increasing the number of generalist physicians" as a major accomplishment to date. To improve their performance, consortium participants call for greater commitment and leadership from the medical school and university, better definition of the community's GME needs, more information about the flow of GME funds locally, greater authority to allocate resources, and incentives for shifting allegiances from individual institutions to the consortium community as a whole. PMID- 7999182 TI - Using "standardized students" to teach a learner-centered approach to ambulatory precepting. PMID- 7999181 TI - Three exemplary models of case-based teaching. AB - Teaching in response to case presentations is an essential feature of clinical teaching in medicine. Yet, this form of case-based teaching is often done poorly. Using qualitative methods of interviews, observations, and recordings of teaching rounds, the author describes three different yet exemplary pedagogical strategies for organizing teaching rounds in general internal medicine. These include: (1) case-bedside teaching that involves case discussion in a conference room followed by demonstrations at the bedside, (2) case-lecture teaching that blends quick reviews of cases with more formal presentations on relevant topics, and (3) case iterative teaching that involves discovery-learning using complex cases. From these three case studies, five general principles of experiential learning in clinical settings are derived: anchoring instruction in cases, actively involving learners, modeling professional thinking and action, providing direction and feedback, and creating a collaborative learning environment. These three approaches to teaching rounds overcome common problems associated with learning in clinical settings. PMID- 7999184 TI - Furthermore... Walking through the fire and signs of spring. PMID- 7999183 TI - Funding for computer-assisted instruction projects. AB - Getting funding for CAI in the education of health professionals is a tough dollar. For resourceful, scholarly applicants with a scientific approach, support is out there. PMID- 7999185 TI - Time is running out for entitlement reform. AB - In 1993, President Clinton created the Bipartisan Commission on Entitlement and Tax Reform as part of the administration's effort to promote economic growth and control the budget deficit. The purpose of the commission, chaired by Senator J. Robert Kerrey (D-NE) and Senator John C. Danforth (R-MO), is to seek bipartisan agreement on long-term entitlement reform and structural changes to the tax system. The final recommendations of the commission, due December 15, will be of great interest to the academic medicine community because of the importance of federal dollars to medical research and education and the crucial role of the Medicare and Medicaid programs in financing the care provided by teaching physicians and teaching hospitals. What follows is a summary of the commission's interim report submitted to the president on August 8; it reflects the commissioners' almost unanimous (30 to 1) agreement on the nature and magnitude of the entitlement problem. PMID- 7999186 TI - Chickens and children do not an expert make. PMID- 7999187 TI - On poultry expertise, precocious kids, and diagnostic reasoning. PMID- 7999188 TI - The importance of defining physicians' competencies: lessons from preventive medicine. PMID- 7999189 TI - Avoiding discriminatory medical school admission and residency interviewing. PMID- 7999190 TI - Useful outline for developing PBL lesson plans. PMID- 7999191 TI - The lecture vs. the journal article. PMID- 7999192 TI - Inpatient database program. PMID- 7999193 TI - Psychosocial approach to medical practice. PMID- 7999194 TI - Does feedback on examination performance help directors of internal medicine residencies evaluate the medical knowledge of their residents against national norms? AB - BACKGROUND: As part of the admission process to the American Board of Internal Medicine's certifying examination in internal medicine, training program directors evaluate residents in several components of clinical competence, including medical knowledge. Research suggested that these ratings had different meanings across programs. A report comparing certifying examination performance and ratings of medical knowledge at the program and national levels was developed and sent to program directors after the 1988 through 1992 examinations. The present study investigated whether feedback helped program directors identify where their residents ranked nationally. METHOD: Subjects were first-time takers of the 1986 through 1992 certifying examinations in internal medicine who took the examination in the year they completed training and who received ratings of 4 through 9 in medical knowledge. All subjects were from programs contributing examinees in all seven study years and that received feedback in 1988 through 1991. Year-by-year distributions of program mean percentages of examinees receiving each rating of medical knowledge (4 through 9) were generated. Program means for equated examination scores and ratings of medical knowledge were computed for each year. Correlations between program mean scores and ratings were also computed. RESULTS: The distributions of the ratings were stable across the study years. Mean scores declined while mean ratings were unchanged. At the same time, correlations between scores and ratings increased. The biggest one-year change was from 1989 to 1990 (.49 to .57). CONCLUSION: Since equated scores are directly comparable, declining mean scores but unchanged mean ratings suggest that the standards applied by program directors drifted downward. The increasing correlations suggest that program directors improved in their abilities to evaluate residents relative to a common standard. It is not clear what effect the feedback had on program directors' evaluations. It is encouraging, however, to see a higher level of agreement among program directors on the meaning of the ratings. PMID- 7999195 TI - The influence of the New Pathway curriculum on Harvard medical students. AB - BACKGROUND: This study evaluated the effect of a radically redesigned curriculum at Harvard Medical School on preclinical students' knowledge, skills, personal characteristics, approaches to learning, and educational experiences. METHOD: Multiple measures were used to collect data from 121 students from the entering classes of 1989 and 1990 who had been randomly assigned to the New Pathway or traditional curricula; all had applied to be in the new curriculum. RESULTS: The New Pathway students reported that they learned in a more reflective manner and memorized less than their control counterparts in the traditional curriculum during the preclinical years. The New Pathway group preferred active learning and demonstrated greater psychosocial knowledge, better relational skills, and more humanistic attitudes. They felt more challenged, had closer relationships with faculty, and were somewhat more anxious than those in the traditional program. There was no difference in problem-solving skills or biomedical knowledge base. CONCLUSION: Students in the new curriculum learned differently, acquired distinctive knowledge, skills, and attitudes, and underwent a more satisfying and challenging preclinical medical school experience without loss of biomedical competence. These findings should encourage other schools to consider such a curriculum. PMID- 7999196 TI - Use of a group objective structured clinical examination with first-year medical students. AB - PURPOSE: To evaluate the implementation of a quarterly group objective structured clinical examination (GOSCE) to assess the patient-evaluation abilities of a medical school class. METHOD: The study subjects were 94 first-year students participating in the Principles of Clinical Medicine course at the Oregon Health Sciences University School of Medicine in 1992-93. To create the GOSCE, the authors modified the format of the quarterly objective structured clinical examination by making each standardized-patient station the site of an interaction between a standardized patient and a group of four or five students. The GOSCE's reliability, content and face validity, and expense were evaluated. Student feedback was obtained using a structured questionnaire. RESULTS: Performances varied both among the five stations of the GOSCE and among the 23 student groups: the mean percentage of items performed correctly per station was 83%, with a range of 73-97%. The reliability of the GOSCE's stations was low, with intraclass correlations during the three consecutive quarters of .29, .05, and .12. Despite no prior experience with this type of testing, the students' mean rating of the GOSCE's appropriateness was 3.8 (on a Likert scale of 1, poor, to 5, excellent), compared with 2.5 for the appropriateness of the written examination also used for quarterly assessment. The expense of the GOSCE was much less than the costs reported for the OSCE format. CONCLUSION: The use of the quarterly GOSCE favorably influenced the students, faculty, and curriculum. The GOSCE format made possible the assessment of a large number of students' abilities, without the time and expense needed to evaluate students individually. PMID- 7999197 TI - Teaching medical students how to perform a clinical breast examination. AB - BACKGROUND: One challenge in medical education is to provide training in physical examination skills. The authors conducted a randomized study to compare standardized and unstandardized methods of teaching clinical breast examinations and to determine whether trained non-medical women could teach as well as medical faculty. METHOD: Sensitivity, specificity, and examination techniques were compared between first-year students at the University of Calgary Faculty of Medicine who in 1992-93 received standardized teaching from family medicine faculty or well women teachers and 70 second-year students who received unstandardized teaching during their clinical rotations. Standardized teaching included a specific examination technique using silicone breast models. The students taught by the well women teachers also examined the women's breasts. RESULTS: The standardized-teaching group had more consistent examination techniques and significantly higher sensitivity but lower specificity. The students taught by the well women teachers performed as well as those taught by the family medicine faculty. CONCLUSIONS: The teaching methods used by trained teachers and standardized models improved the students'accuracy of breast lump detection and examination skills. PMID- 7999198 TI - First-year residents' caring, medical knowledge, and clinical judgment in relation to laboratory utilization. AB - PURPOSE: To investigate first-year residents' levels of caring (concern for others' well-being), medical knowledge, and clinical judgment in relation to their levels of laboratory utilization. METHOD: Self-report questionnaires about caring, knowledge, and judgment were given in 1986-87 to 36 first-year residents in a three-year internal medicine residency program of the McGaw Medical Center of Northwestern University. Inpatient laboratory utilization data obtained from structured chart audits over a one-year period were used to construct comparable diagnosis- and severity-specific physician practice profiles, from which the residents received overall utilization scores for laboratory test charges. Statistical methods included Cronbach's alpha reliability coefficient and multiple regression analysis. RESULTS: The multiple regression analysis showed that medical knowledge was an independent predictor of increased laboratory utilization (standardized beta = .54, p < .04, partial R2 = .07); clinical judgment was an independent predictor of decreased utilization (standardized beta = -.53, p < .05, partial R2 = .06); and caring was unrelated to utilization (standardized beta = .15, ns, partial R2 = .01). CONCLUSION: The finding that clinical judgment was related to less laboratory utilization suggests that future research should investigate the decision-making concomitants of judgment to better understand its translation into resource utilization. It is possible that the relationship between medical knowledge and laboratory utilization is developmentally specific, and thus the knowledge of more experienced physicians, who would likely be more precise decision makers than first-year residents, may be related to decreased rather than increased utilization. PMID- 7999199 TI - The effect of a class in medical ethics on first-year medical students. AB - PURPOSE: To assess the effect of a class in medical ethics on first-year medical students. METHOD: A test instrument was developed to measure the attitudes of medical students toward certain ethical questions and to assess their factual knowledge regarding particular legal and ethical issues. The instrument was administered in 1992-93 to 110 first-year students at the University of Virginia School of Medicine before and after the students took a required course in medical ethics. The instrument employed clinical vignettes as well as multiple choice, true-false, and Likert-scale questions. Its reliability and validity were assessed. RESULTS: The required course in medical ethics had little influence on the students. There was only one significant change (p = .05) in the pattern of responses to any of the clinical vignettes. In a few of the attitude-oriented queries, there were statistically significant changes (p < .05) after the course. Although there were statistically significant changes for only four of the factual-knowledge questions, for all such questions more students identified the correct answers after the class (before the course the range of correct answers was 43% to 99% compared with 64% to 100% after the course). CONCLUSION: The class in medical ethics seemed to have little effect on the first-year students, probably because students arrive at medical school with well-established ethical perspectives. PMID- 7999200 TI - The connection between risky driving and involvement in fatal accidents. AB - The connection between risky driving and involvement in fatal accidents was investigated in two studies using two data sets. The first study compared the recorded offenses of 615 drivers involved in fatal accidents with a sample of drivers randomly selected from driver records. The second study compared the recorded offenses of 143 drivers stopped by the police for risky driving with the prior records of control drivers stopped at the same locations. The drives involved in fatal accidents and the drivers stopped for risky driving had violated traffic regulations more often than other drivers. Those responsible for causing fatal accidents as well as involved but nonculpable drivers had previously been convicted of traffic offenses more often than other drivers. Among the fatal-accident drivers, those involved in running-off-the-road accidents had accumulated the largest number of traffic offenses. There appears to be a particular link between the age and the prior offense rate of the two risk groups. For under-35-year-olds, the offense rate (offenses/million kilometers) of those stopped for risky driving and those involved in fatal accidents were about the same. For over-35-year-olds, the drivers stopped for risky driving had accumulated many times more speeding offenses than those involved in fatal accidents. Unlike the other groups the offense rate of those stopped for risky driving does not decrease with age. PMID- 7999201 TI - A method of estimating linear and angular accelerations in head impacts to pedestrians. AB - In order to investigate the relationship between impact to the head and brain injury, we have developed a method, using information obtained from reconstruction of the collisions, of estimating the peak linear and angular accelerations of the head for pedestrian impacts on a vehicle. This information includes the location of the impact on the head, the impact velocity of the head, and the stiffness of the struck surface. In developing the method we assumed that the velocity of the head on striking the vehicle was the same as the velocity of the vehicle itself, that the force vector was normal to the surface of the skull, that the force-deflection curve characterising the combined response of the impacted surfaces was linear, and that the kinetic energy of the head immediately prior to impact was converted into strain energy in deforming the head and the vehicle structure. Only the loading phase of the impact was considered, there was no assumption of an elastic unloading phase. Using cadavers, the validity of these assumptions and hence the usefulness of the method were tested by comparing the estimates of peak linear acceleration with the results of 18 pedestrian vehicle impact reconstructions. On average, the method underestimated the experimental values by about 15%, with a range of +/- 35%. The results from the application of this method are currently being used to study the relationship between the magnitude and direction of the impact to the head and the distribution and severity of the brain injury resulting from actual collisions. PMID- 7999202 TI - Evaluation of driver drowsiness by trained raters. AB - Drowsiness of vehicle operators is a major hazard in transportation systems, and methods need to be developed for practical evaluation of drowsiness level. One suggested approach is observer rating. Accordingly, an experiment was carried out using trained observer-raters to evaluate the levels of drowsiness of drivers, the drivers' faces were recorded on videotape. Videotaped segments of drivers at various stages of drowsiness were presented in two sessions separated by a time interval of one week. The experiment was directed at determining test-retest reliability, interrater reliability, intrarater reliability, and consistency. Results indicate that such ratings are reliable and consistent. A subsequent experiment shows that ratings covary with other known indicators of drowsiness. PMID- 7999204 TI - Simulation of traffic conflicts at unsignalized intersections with TSC-Sim. AB - This paper describes a traffic conflicts computer simulation model and graphic display for both T and 4-leg unsignalized intersections. The goal of the model is to study traffic conflicts as critical-event traffic situations and the effect of driver and traffic parameters on the occurrence of conflicts. The analysis extends conventional gap acceptance criteria to describe driver's behaviour at unsignalized intersections by combining some aspects of gap acceptance criteria and the effect of several parameters including driver's characteristics such as age, sex, and waiting time. The effect of different traffic parameters such as volume and speed on the number and severity of traffic conflicts is also investigated. The model is unique insofar as it uses a technique of importance sampling and stores the traffic conflicts that occur during the simulation for later study. A graphical animation display is used to show how these conflicts occurred and the values of critical variables at the time. Model results were evaluated against previous work in the literature and validated by using field observations from four unsignalized intersections. The simulation results correlated reasonably well with actual conflict observations and should prove useful for assessing safety performance and feasible solutions for other unsignalized intersections. PMID- 7999203 TI - Incidence and cost of alcohol-involved crashes in the United States. AB - The incidence of alcohol-involved highway crashes (those in which a driver or nonoccupant had been drinking) was estimated from federal data bases. The estimates were adjusted for police underreporting of alcohol involvement. In 1990, 22% of motor vehicle crash victims--1.2 million--were injured in crashes involving alcohol. Over 22,000 of these victims were killed. The comprehensive cost of alcohol-involved crashes was $148 billion in 1990, including $46 billion in monetary costs and $102 billion in lost quality of life. This represents $1.09 per drink of alcohol consumed. Crashes where blood alcohol concentration (BAC) exceeded .10% accounted for 32% of comprehensive crash costs, and crashes with lower positive BAC accounted for another 8%. Excluding drunk drivers and drunk nonoccupants, alcohol-involved crashes caused 8,500 deaths and left 21,000 people permanently disabled and another 605,000 less seriously injured. Averaged across all drinks, other people collectively pay $0.63 in crash costs every time someone takes a drink. A combination of increased public awareness and strong legal sanctions has been effective in reducing the incidence of alcohol-involved driving. The proportion of injuries in crashes that police reported were alcohol involved dropped by 37% between 1982-1984 and 1990. PMID- 7999205 TI - Driver injury and fatality risk in two-car crashes versus mass ratio inferred using Newtonian mechanics. AB - This paper aims at explaining the results of a recent empirical study that found that when cars of unequal mass crash into each other, the ratio of driver fatality risk in the lighter care to risk in the heavier car (the fatality risk ratio) increased as a power function of the ratio of the mass of the heavier car to that of the lighter car (the mass ratio). The present study uses two sources of information to examine the relationship between these same quantities: first, calculations based on Newtonian mechanics, which show that when two cars crash head-on into each other, the ratio of their changes in speed (delta-v) is inversely proportional to mass ratio; second, National Accident Sampling System data, which show how delta-v affects driver injury risk. The study is performed for fatalities and severe injuries and for unbelted and belted drivers. Combining the two sources of information gives the result that fatality risk ratio increases as a power function of mass ratio, the same functional form found in the empirical study. Because the study is rooted in Newtonian mechanics, it clearly and directly identifies physical mechanisms involved and leads to the conclusion that mass, as such, causes large differences in driver injury and fatality risk when cars of unequal mass crash into each other. PMID- 7999206 TI - Tiredness and visual reaction time among young male nighttime drivers: a roadside survey. AB - The study focus on the incidence and importance of tiredness among young male car drivers in nighttime traffic. It took place on a major highway in Copenhagen County, Denmark, and was performed as roadside surveys in the hours between midnight and 6 A.M. The study consisted of a questionnaire with self-assessment of tiredness followed by a simple visual reaction-time test. Two hundred and forty nighttime drivers and 40 early morning drivers joined the study. One hundred and twenty-three nighttime drivers declared themselves as rested, 106 as tired, and 11 as very tired. Thirty-seven early morning drivers declared themselves as rested, while the remaining three declared themselves as tired. The drivers' self-assessed level of tiredness corresponded well with the results of the simple visual reaction-time test, but one self-declared tired driver had to be reclassified as very tired. The visual reaction-time test henceforth showed a mean reaction time of 0.189 seconds for the rested drivers, 0.223 seconds for the tired, and 0.309 seconds for the very tired nighttime drivers (p < .001). Mean reaction time for the early morning drivers was 0.190 seconds corresponding to 0.246 seconds in the equivalent nighttime group (p < .001). The fluctuations in mean reaction time throughout the night for the whole population including the early morning drivers correlated well with the number of tired/very tired drivers (corr. = 0.96). The study shows tiredness as a common affliction among young male nighttime drivers. PMID- 7999207 TI - The impact of a media campaign in the reduction of risk-taking behavior on the part of drivers. AB - As part of an ongoing media educational campaign to enhance pedestrian safety in the Victoria (Canada) metropolitan area, multimedia campaigns have been targeted at drivers. This paper evaluates the campaign that focused on encouraging left turning drivers to yield. Observers monitored five signalized intersections during five separate weeks. Logistic regression analyses indicate that this media campaign produced a long-term effect of increasing drivers' yielding behaviors. PMID- 7999208 TI - Characteristics, hospital charges, and effects of road transportation injuries in Vermont. AB - We studied 470 crash- and noncrash-related road transportation injuries to vehicle occupants, bicyclists, and pedestrians seen at a trauma center in Vermont. Among primary care patients, crash and noncrash groups had similar AIS and average disability at one year. Hospitalized patients had longer disability, but a majority of overall disability days and ongoing disability was found among nonhospitalized patients. Seventy-four percent of hospital bills were paid by insurance, 16% by government, 3% by self, with 7% unpaid. Limiting the sample only to hospitalized patients, or including referred patients, markedly affected- but in different ways--distributions of event type, body area injured, charges, and other characteristics. PMID- 7999210 TI - Heavy drinking and the risk of occupational injury. AB - This study evaluated the association between the frequency of heavy drinking and the risk of occupational injury, using nationally representative data from the 1988 National Health Interview Survey (NHIS). The sample consisted of 29,192 adults who were employed at some time during the year preceding the NHIS interview. Overall, 7.2% reported an on-the-job injury during the preceding year, but the rates were higher--about 13%--for those employed as skilled or unskilled laborers or who reported engaging in repeated strenuous physical activity at work. Slightly more than one-fourth of the employed adults reported at least one occasion of drinking five or more drinks during the preceding year. After adjusting for the effects of age, gender, education, occupation, and strenuous job activity, the odds of occupational injury increased with frequency of heavy drinking, with odds ratios varying from 1.08 (one occasion of heavy drinking) to 1.74 (daily heavy drinking). Odds ratios were decreased slightly by the inclusion of smoking as a control variable, indicating that some of the excess risk of injury among heavy drinkers may reflect their greater propensity to take health related risks rather than direct effects of ethanol. The odds ratios also were slightly lower when the analysis was restricted to current drinkers, suggesting that the risk of work injury was increased by light or moderate as well as heavy drinking. PMID- 7999209 TI - The Grand Rapids dip revisited. AB - This analysis addresses an issue that has concerned road safety authorities for some 28 years: the celebrated "Grand Rapids Dip." This, most readers will recognise, is the below-baseline excursion, which occurs in the blood alcohol concentration (BAC) interval of .01%-.04%, of the relative risk curve for accident risk versus blood alcohol, derived from the 1964 Grand Rapids Study data. The present analysis has its starting place in the explanation advanced by Allsop, who noted that the case/control comparisons were biased due to the disproportionate representation of demographic subgroups in different blood alcohol concentration class intervals. Indeed, when relative-risk curves are derived separately for subgroups of differing drinking habits, the resulting separate risk curves all show monotonic increases at all blood alcohol concentration ranges. Such separate relative risk curves are unpopular, and most of the road safety community pays them little heed. Thus, the original concept of the "dip" remains with us. For this reason, we have derived, using a simple but realistic statistical model, a single relative-hazard curve from the Grand Rapids data, one that is free from the distortion introduced by unequal representation of different demographic subgroups in different blood alcohol concentration class intervals. This curve indicates that accident risk increases with increased blood alcohol concentration regardless of self-reported drinking frequency. However more frequent drinkers have less risk at all blood alcohol concentration levels, including zero, than less frequent drinkers at the times and places sampled. PMID- 7999211 TI - Increasing child safety-seat use and proper use among toddlers. Evaluation of an enforcement and education program. AB - Effective enforcement programs to promote use and proper use of child safety seats can be successfully implemented. This paper describes the evaluation of a combined occupant-restraint enforcement program plus a public-information and education program conducted in two test sites and one comparison site; all three are suburban communities of Philadelphia, Pennsylvania. The program was successful in increasing toddler use of child seats from a baseline of 71.8% and 60.9% to 76.8% and 71.4%, respectively, and in increasing proper use of seats from a baseline of 67% and 57.5% to 72.8% and 69.3%, respectively, in the two test communities. This paper details program and evaluation activities, suggests future directions for improving occupant restraint programs, and describes research techniques for better understanding the effects of enforcement and education on child safety-seat use and proper use. PMID- 7999212 TI - The incidence of stairway injuries in Austria. AB - Stairs are among the most hazardous features of the everyday environment, yet stairway falls have received little research attention. A stratified random sample of Austrian residents was surveyed in person in 1989. Of over 55,000 respondents, 147 reported a stairway injury in the previous year that limited activity for at least one day. Thirty-seven percent of these injuries resulted in hospitalization. Extrapolating to the entire country of 8 million people, each year some 20,000 Austrians sustain serious stairway injuries resulting in over 7,500 hospitalizations. The incidence of stairway injury increases monotonically with age, and females are more at risk than males. The stereotypical stairway injury victim is an elderly woman, not highly educated, who is unmarried and living alone. PMID- 7999213 TI - Injuries missed during initial assessment of blunt trauma patients. AB - OBJECTIVE: To determine the incidence and clinical significance of undiagnosed injuries in blunt trauma patients at our institution. DESIGN: Retrospective analysis of blunt trauma admissions over a 1-year period. Missed injury (MI) was defined as any injury recorded after the initial 24 hours. RESULTS: Of 432 patients studied, 59 (13.6%) had MI. Fractures were the most common MI. Thirty five percent of MI were detected during repeated physical examination and 28% after patients were conscious and able to voice concerns. CONCLUSION: Over 10% of all blunt trauma patients had undiagnosed injuries. Forty percent of the MI had clinical implications. The most effective method of diagnosis consists of repeated clinical assessments. Special attention should be focused on patients with severe anatomical injuries, obtunded or intubated. PMID- 7999214 TI - Global trends in health care reform. AB - Health systems throughout the world are hard pressed to curb costs and safeguard quality. In general, the users of health services are having to pay more for them, and in some cases this is making the system unsustainable. Even where costs can be met, the payment mechanisms used can make a decisive difference in terms of equity and efficiency. PMID- 7999215 TI - Between Beveridge and Bismarck--options for health care financing in central and eastern Europe. AB - A government-run national health service (the Beveridge model) can provide care for all at a reasonable cost but cannot avoid the dangers of poor quality. An insurance-based system (the Bismarck model) can achieve high quality but cannot ensure care for all at an affordable cost. The best chance of achieving a reliable financial base for health services is to use a combination of both these approaches. PMID- 7999216 TI - Private and public financing--health care reform in eastern and central Europe. AB - There are conspicuous limits to what privatization and the free play of market forces can do for health care. In particular, they cannot ensure access, adequacy and affordability for users. Therefore, in moving from a centrally planned economy, governments need to take care to avoid some of the costly mistakes that have been made in western countries. PMID- 7999217 TI - Post-Soviet public health administration in Estonia. AB - Estonia's administrative legacy presents a number of difficult challenges for the health services. The system which was designed as part of a gigantic centrally controlled bureaucracy now has to be adapted to the needs of a small independent country. PMID- 7999218 TI - How disease prevention fails without good communication. AB - Even where resources are plentiful, efforts to achieve full immunization coverage fail if staff and users are misinformed and unmotivated. A highly practical study in Lagos pinpoints some of these failures and suggests ways of overcoming them. PMID- 7999219 TI - Conscripts for health. PMID- 7999220 TI - Winners show the way to good management in health care. AB - To stimulate resourcefulness in the health care services of the Philippines, the German Agency for Technical Cooperation (GTZ) organized a competition to discover and publicize examples of good management. The results provide a rich fund of new ideas. PMID- 7999221 TI - Health and culture in urban planning. AB - Rapid change, driven mainly by business and technology, has transformed our understanding of health and living conditions in recent decades. Experiments in urban development in Japan are bringing together technology, quality of life, culture and business to satisfy the needs of human health and well-being. PMID- 7999223 TI - Solid waste disposal in district health facilities. AB - Hospital waste is not necessarily difficult to dispose of. In most cases it can be safely dumped in a properly designed waste pit. Waste management problems at district hospitals in developing countries are usually caused more by lack of information than by financial or technical difficulties. PMID- 7999222 TI - Promoting sanitation in Bangladesh. AB - A community-level survey was made in Bangladesh to assess the effectiveness of a health promotion campaign on sanitation. The data collected showed that the mobilization of schoolchildren to promote the construction and use of sanitary latrines had a significant impact on local practices. Poorer families appeared to be more responsive to the idea of building their own sanitary latrines than those who were slightly better off, who sometimes saw the homemade latrine as a symbol of low status. In several cases the woman of the household did the construction work rather than the man, and this aspect of women's participation could usefully be emphasized in future campaigns. PMID- 7999224 TI - District health libraries. PMID- 7999225 TI - District health libraries. PMID- 7999226 TI - Reflections of a psychoanalyst. PMID- 7999227 TI - No place for herbalists in modern medicine. PMID- 7999228 TI - Impediments to breast-feeding in hospitals. PMID- 7999229 TI - When do we need to use statistics? PMID- 7999230 TI - Health for all on the road. PMID- 7999231 TI - Insulin: availability and cost. PMID- 7999232 TI - Family planning and tradition: a view from northern Cameroon. AB - Sometimes efforts to improve the quality of life can hasten the destruction of a whole way of life, in which case the "beneficiaries" can lose much more than they gain. This presents health workers and planners with difficult choices. PMID- 7999233 TI - Double think and double talk. AB - The public health debate on population growth and child mortality continues, fuelled by the hypothesis that in allowing more children to survive until reproductive age, programmes such as the Diarrhoeal Diseases Control Programme of the World Health Organization contribute to long-term human misery by overburdening the carrying capacity of the planet. A significant part of the solution put forward is to withhold public health services to children in developing countries. This argument is here refuted on socioeconomic, ethical and humanitarian grounds. An alternative approach is offered, which takes into account the economic and social obligations of the industrialized nations. PMID- 7999234 TI - Schistosomiasis control in China. AB - Well-organized programmes combining local involvement and major government projects have been successful in controlling schistosomiasis to a large extent in China. The task is far from complete, however, especially in some lacustrine and mountainous areas, where conditions are highly favourable for the vector snails, and difficult to modify. A long-term programme of health education, medical care and infrastructure development is needed. PMID- 7999235 TI - Traditional healers in Casamance, Senegal. AB - As part of a long-standing effort to foster collaboration between Western and traditional health workers, the writers talked with six animist healers and marabouts about their work. They begin with some general information about traditional healing in Casamance, a region in southern Senegal. PMID- 7999237 TI - Infant feeding--some lessons from Yangon. PMID- 7999236 TI - Food safety in primary health care. AB - Efforts to ensure food safety through legislation have been only partially successful, and the prevalence of foodborne disease is increasing in most countries. Health education on a large scale is needed to raise the level of public awareness of the factors leading to the spread of these diseases. The best way to do this is through the primary health care system, basing activities on both scientific knowledge and local food-related customs and behaviour. PMID- 7999238 TI - Let pharmacists do more for health in developing countries. AB - It is desirable that the role of the pharmacist be expanded in developing countries, particularly with a view to coping with the problems of poor access to essential drugs and the irrational use of drugs. This objective requires improved collaboration between the medical and pharmacy professions. PMID- 7999239 TI - The menace of substandard drugs. AB - Numerous small pharmaceutical manufacturers in Bangladesh are marketing substandard drugs, often deliberately using inadequate levels of active ingredients. Stricter application of the national drug policy is necessary, notably in regard to the issuing of licences and the sanctions applied to firms breaking the law. PMID- 7999240 TI - A training project for disability prevention in Malawi. AB - Musculoskeletal disorders affect an estimated 3% of the population in Malawi. The vast majority of them can be treated by orthopaedic clinical officers who are deployed to the district hospitals after 18 months of training. This article describes a project designed to provide the training, and evaluates its impact after seven years in operation. PMID- 7999241 TI - Offensive against rabies in Europe. PMID- 7999242 TI - Community action for health. PMID- 7999243 TI - The Global Commission on Women's Health. PMID- 7999244 TI - WHO leads action against female genital mutilation. PMID- 7999245 TI - Cervical cancer vaccine prospects. PMID- 7999247 TI - Good prospects for leprosy target. PMID- 7999246 TI - Tuberculosis on the increase in Eastern Europe. PMID- 7999248 TI - Medical school updates. PMID- 7999249 TI - First International Conference on Elimination of Leprosy. PMID- 7999250 TI - World's biggest heart attack study. PMID- 7999251 TI - Follistatin but not alpha or beta A inhibin subunit mRNA is expressed in ovine fetal ovaries in late gestation. AB - The aim of this study was to investigate the sites of follistatin and alpha and beta A inhibin mRNA expression in the ovaries of female sheep fetuses at 90, 100, 120 and 135 days of gestation (term = day 147). At 90 and 100 days primordial follicles were formed, followed by the appearance of primary follicles at 100 days of gestation. At days 120 and 135, primordial, primary and preantral (i.e. secondary) follicles were present in the ovaries, but antral (i.e. tertiary) follicles were not observed at any of these gestational ages. Two Booroola genotypes were studied: homozygous carriers (BB) and non-carriers (++) of the fecundity gene (FecB). Irrespective of genotype no specific hybridization of the alpha and beta A inhibin riboprobes was detected in any ovarian cells at days 90, 100, 120 or 135 of gestation. In control mature ovaries, on the other hand, strong hybridization in the granulosa cells of antral follicles was observed. In contrast to alpha and beta A inhibin, follistatin antisense (but not sense) riboprobes hybridized specifically to the granulosa cells of preantral follicles with two or more layers of cells at days 120 and 135 of gestation. Moreover, hybridization was also evident in the cells of the ovarian rete at days 120 and 135, but not at 90 or 100 days. No follistatin mRNA expression was observed in the granulosa cells of primordial or primary follicles or in any other ovarian cell type at any of the gestational ages examined.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7999252 TI - Overexpression of the extracellular domain of the thyrotrophin receptor in bacteria; production of thyrotrophin-binding inhibiting immunoglobulins. AB - The availability of high affinity antibodies to the human TSH receptor (TSHR) would help in defining its functional domains, but this requires the production of pure receptor as immunogen. We have expressed the extracellular domain (ECD) of the TSHR (residues 21-414) as a fusion protein with maltose-binding protein (MBP) in Escherichia coli, using the pMAL-cR1 vector. The major protein in an electrophoretically separated, crude bacterial lysate had a molecular mass of 89 kDa, in agreement with the size predicted for the MBP-ECD fusion product. Its identity was confirmed by Western blotting in which it was recognized by two polyclonal antibodies to synthetic peptides of the TSHR and an anti-MBP. Following purification on an amylose column, 15 mg pure MBP-ECD per litre of culture were produced, which was 5% of the total bacterial protein. Following extensive dialysis in a buffer which produces slight denaturation, MBP-ECD was cleaved with factor Xa. The identity of each protein was confirmed by Western blotting. To investigate the possibility of using the fusion protein as an immunogen we produced rabbit polyclonal antibodies to the ECD which were able to produce immunofluorescent staining of Chinese hamster ovary cells that expressed the TSHR, and revealed a protein of 95 kDa in Western blots of the same cells, in addition to a protein of 55 kDa. Only the protein of 55 kDa was detected in Western blots of human thyroid membranes.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7999254 TI - Negative control of the rat inhibin alpha subunit promoter in MA-10 Leydig tumour cells. AB - The promoter/regulatory sequences responsible for the transcription of the rat inhibin alpha subunit gene in the testis were identified by the transient expression in an MA-10 Leydig tumour cell line of a bacterial reporter gene, chloramphenicol acetyltransferase (CAT), which was driven by different regions of the 5' flanking sequence of the inhibin alpha subunit gene. The CAT activity was elevated when the 2.0 kb 5' flanking alpha subunit gene fragment was progressively shortened from its 5' end, and a maximal increase was reached when the CAT gene was driven by an alpha subunit gene promoter extending to -163 bp. This construct was termed A alpha BstCAT. Furthermore, when either the -2.0 to 1.6 kb or the -2.0 to -1.0 kb alpha subunit DNA fragment was fused to A alpha BstCAT, and CAT activity was markedly suppressed, indicating the presence of negative regulatory DNA elements (NREs) in the upstream region of the gene. The cyclic AMP (cAMP) responsiveness of the alpha subunit gene, which was dependent upon the putative cAMP response element within the 67 bp alpha subunit promoter, was not affected by the upstream NREs. The inhibitory effect was also demonstrated when the -2.0 to -1.0 kb fragment was placed in either orientation with respect to the alpha subunit promoter or to a thymidine kinase promoter, suggesting that the NRE(s) can act as a silencer. Based on our observations we conclude that the basal expression of the rat inhibin alpha subunit gene in testicular MA-10 cells may, at least in part, be controlled by the upstream silencer(s) and NRE(s). PMID- 7999253 TI - Pregnancy-related modifications of rat myometrial Gs proteins: ADP ribosylation, immunoreactivity and gene expression studies. AB - Previous studies from our laboratory have suggested that post-receptor events at the level of beta-adrenergic receptor-adenylate cyclase interaction could be altered in myometrium by steroid hormones or pregnancy. In this study, we have addressed this question by performing a direct evaluation of rat myometrial Gs proteins at various stages of pregnancy or 24 h after administration of progesterone. In the 50,000 g myometrial plasma membrane fraction, in the presence of 32P-labelled NAD, cholera toxin ribosylated three predominant proteins with apparent molecular masses of 42, 47 and 55 kDa. Western blot analysis using the RM/1 antibody recognized the 42 and 47 kDa cholera toxin ADP ribosylated bands but not the 55 kDa band. Thus, the 42 and 47 kDa immunoreactive bands were interpreted as being the small (Gs alpha-S) and large (Gs alpha-L) forms of Gs respectively. With a more purified myometrial plasma membrane fraction (105,000 g) an additional minor band of 44 kDa could be observed with both techniques. Treatment of late pregnant rats with 5 mg progesterone resulted in a significant increase in both Gs alpha subunits: +25% and +30% after ADP ribosylation, +50% and +60% after Western blot analysis for Gs alpha-L and Gs alpha-S respectively. Pretreatment with the antiprogestin RU 486 completely suppressed the effect of progesterone, suggesting that the expression of Gs alpha subunits may be under the control of progesterone. However, changes in the myometrial content of Gs in progesterone-treated rats were not associated with concomitant variations in the steady-state levels of mRNA as demonstrated by Northern blot analysis. These data suggest a post-translational regulation of Gs expression by progesterone. Amounts of ADP-ribosylated Gs showed characteristic changes during the course of pregnancy with a fourfold or threefold increase (P < 0.05) on day 15 versus day 12 or delivery respectively. During pregnancy, or after progesterone administration, myometrial alterations of Gs strongly correlated (r = 0.913, P < 0.01) with the cholera toxin-stimulated adenylate cyclase activity. These findings provide evidence that changes in myometrial amounts of functional Gs i) are controlled by the hormonal status of pregnancy and progesterone and ii) play an important role in the transduction pattern of adenylate cyclase activity during the course of pregnancy. PMID- 7999255 TI - Regulators for the rat clusterin gene: DNA methylation and cis-acting regulatory elements. AB - Clusterin, also known as sulphated glycoprotein-2 or testosterone-repressed prostate message-2, is a ubiquitous protein found in a variety of tissues and species. In the reproductive tract of the male rat, clusterin is regulated in a complex age-dependent and cell-specific manner. It is expressed at high levels in the epididymis and testis and at very low levels in the prostate under basal conditions. The expression of this gene in the prostate and seminal vesicles is associated with androgen withdrawal, while in the testis clusterin mRNA is repressed by cyclic AMP (cAMP). To understand the mechanisms that control the expression of the clusterin gene better, we isolated and characterized the gene encoding rat clusterin, and analysed its cytosine methylation pattern in various tissues. Several putative regulatory DNA elements were identified, including a consensus AP-1 site in the 5' flanking region. Two AP-1 sites and two transforming growth factor-beta inhibitory elements, one AP-2 site and eight half sites for glucocorticoid/androgen response elements were found within the first intron, and one cAMP response element was found in the first exon. The cytosine methylation pattern indicated that testicular or epididymal DNA in the rat is hypomethylated in the region between positions -534 and -99 of the clusterin gene, when compared with tissues with lower levels of expression such as prostate as well as liver, lung, kidney and spleen. PMID- 7999256 TI - Molecular cloning, sequence analysis and expression of human pituitary glutaminyl cyclase. AB - A cDNA clone for glutaminyl cyclase was isolated from a human pituitary cDNA library and the complete DNA sequence determined. The cDNA clone had 1573 bp and contained an open reading frame of 1086 bases, coding for a protein of 361 amino acids and molecular mass of 40,876 Da. The predicted amino acid sequence of the human cDNA showed 86% sequence identity to the previously reported bovine glutaminyl cyclase sequence. A comparison of the amino acid sequences derived from the human and bovine cDNAs showed that several glycosylation and phosphorylation sites as well as two cysteine residues (Cys139, Cys164) were conserved. The human cDNA was cloned into the Escherichia coli expression vectors pMALc2 and pET19b. Expression of this cDNA in either vector resulted in the production of a glutaminyl cyclase fusion protein which was enzymatically active and reacted with anti-bovine glutaminyl cyclase antisera. Substrate specificity studies with the recombinant enzyme suggested a bias against acidic and tryptophan residues adjacent to the N-terminal glutaminyl residue and a lack of importance of chain length after the second residue. PMID- 7999257 TI - Suppression of luteal steroidogenesis by an LHRH antagonist (Nal-Lys antagonist: antide) in vitro during early pregnancy in the rat. AB - LHRH and its analogues are known to exert direct effects on the ovary. Herein we have described a direct inhibitory effect of an LHRH antagonist (Nal-Lys antagonist: antide) on the basal progesterone (P4) and pregnenolone (P5) production by luteal cells obtained from the day-8 pregnant rat. Luteal cells incubated with two doses of antide (10(-4) and 10(-7) M) for 24 or 48 h showed suppression of P4 production. P5 production was suppressed by both doses of antide within 12 h of incubation. Neither dose of antide interfered with P5 production when the duration of incubation was extended beyond 12 h. The 20 alpha dihydroprogesterone yield from the luteal cells treated with these doses of antide remained unaffected. We estimated the activities of the cholesterol side chain cleavage (P450scc) enzyme (which is a key enzyme involved in the conversion of cholesterol to P5) and 3 beta-hydroxysteroid dehydrogenase (3 beta-HSD) (which catalyses the conversion of P5 to P4) in the luteal cells treated with different doses of antide. Both doses of antide suppressed the activity of the P450scc enzyme after 12 h of incubation and the 3 beta-HSD content of the luteal cells after 48 h of incubation. These observations indicate that antide exerts a direct inhibitory effect at the level of the corpus luteum, that differential suppression of P5 and P4 during different periods of incubation with antide is due to a defect in either the P450scc or the 3 beta-HSD enzyme system, or both. PMID- 7999258 TI - Alpha-melanocyte-stimulating hormone-induced inhibition of angiotensin II receptor-mediated events in the rat adrenal zona glomerulosa. AB - It is well established that ACTH and angiotensin II (Ang II) stimulate aldosterone secretion from rat adrenal zona glomerulosa cells in vitro and mediate their steroidogenic effects via the cyclic AMP (cAMP) pathway and phosphoinositide turnover respectively. alpha-MSH also stimulates aldosterone secretion from zona glomerulosa cells in vitro, and recent studies from our laboratory have shown that its steroidogenic effects are mediated by increases in inositol 1,4,5-trisphosphate (IP3) production. alpha-MSH also stimulates adenylyl cyclase activity, but only at concentrations that are supramaximal for stimulation of steroidogenesis. The observation that alpha-MSH-stimulated IP3 accumulation declines as the activity of adenylyl cyclase increases prompted further studies on the interactions of cAMP and phosphoinositide production. The effects of alpha-MSH and ACTH on Ang II-stimulated steroidogenesis and IP3 accumulation were studied. On addition of increasing concentrations of ACTH, both the aldosterone and IP3 responses to Ang II were significantly inhibited; however, only high concentrations of alpha-MSH achieved this effect. These results suggest that cAMP or a cAMP-dependent event is able to inhibit phospholipase C activity. This hypothesis was tested by measuring IP3 production in Ang II-stimulated zona glomerulosa cells exposed to two different concentrations of alpha-MSH: 1 nmol/l, which stimulates the generation of IP3, and 1 mumol/l, which activates adenylyl cyclase. It was found that this high concentration of alpha-MSH significantly inhibited Ang II-stimulated aldosterone secretion and IP3 levels. In addition, alpha-MSH reduced 125I-labelled Ang II binding to rat adrenal zona glomerulosa cells.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7999259 TI - Hypomethylation of DNA: an epigenetic mechanism involved in tumor promotion. PMID- 7999260 TI - Oncogene amplification per se: an independent prognostic factor in human breast cancer. AB - As the prognostic significance of the three most frequently amplified oncogenes in breast cancer (c-myc, int-2/FGF3, and c-erbB-2/neu) is still unclear, and as the amplification of these genes appears to be mutually exclusive, we investigated the prognostic significance of oncogene amplification per se by multivariate analysis in a group of 112 primary human breast cancer cases. Amplification of at least one gene (c-myc, int-2/FGF3, or c-erbB-2/neu), progesterone receptor status, and pathological tumor size were the only independent variables predictive of metastasis-free survival. Moreover, we constructed prognostic profiles by computing risks associated with the three parameters predictive of poor survival and discriminated high-, moderate-, and low-risk categories. PMID- 7999261 TI - Expression of multiple isoforms of protein kinase C in normal human colon mucosa and colon tumors and decreased levels of protein kinase C beta and eta mRNAs in the tumors. AB - Previous studies have suggested that protein kinase C (PKC) may play an important role in colon carcinogenesis and that human colon tumors have less total PKC enzyme activity than normal tissue. Because PKC is a multigene family that encodes for at least 11 distinct isoforms, in the study reported here we analyzed the expression of six of these isoforms at the mRNA level by northern blot hybridization in 22 pairs of primary colon tumors (of various stages), and adjacent normal mucosa samples. We found that the normal mucosa samples expressed the mRNAs of the following isoforms of PKC, in decreasing order of abundance: PKC delta > PKC eta > PKC alpha > PKC beta > PKC epsilon. There was no consistent difference in the levels of PKC alpha, PKC delta, and PKC epsilon mRNAs between the normal mucosa and the tumor samples. PKC gamma was expressed at a very low level in two of the colon tumors but could not be detected in the remaining tumors or any of the normal mucosa samples. The levels of both PKC beta and PKC eta mRNAs were significantly lower in the tumor samples than in the normal mucosa samples, and this was true of adenomas as well as Dukes' stage A, B, and C adenocarcinomas. Furthermore, the decrease in PKC eta mRNA appeared to be greater in the more poorly differentiated carcinomas. This finding is of interest because PKC eta is normally expressed in the more differentiated cells of epithelial tissues. The decreased levels of both PKC beta and PKC eta mRNAs occurred early in the multistage process of colon carcinogenesis, as it was also seen in adenomas. The functional significance of these changes remains to be determined. PMID- 7999262 TI - Analysis of transcriptional activation of a cyclic AMP response element by 2,6,10,14-tetramethylpentadecane (pristane) in JB6 mouse epidermal cells. AB - Pristane is a naturally occurring isoprenoid that is believed to be derived from the phytyl moiety of chlorophyll. Thus, it is not surprising that pristane is present in many common fruits and vegetables. Furthermore, pristane can be detected in the tissues of fish and mammals. In animal models using rodents, pristane can function as a potent tumor promoter. At the molecular level, pristane can induce changes in the plasma membrane, alter the conformation of chromatin, and selectively activate gene expression. Addition of pristane to a mouse epidermal cell line (JB6 P+) allows these cells to grow in an anchorage independent manner. In contrast, JB6 P-cells are not transformed by pristane. Our study was undertaken to correlate transformation of P+ cells with changes induced by pristane. Transcriptional activation of a cyclic AMP response element (CRE) was induced by pristane in P+ and P-cells. Point mutations in the CRE abolished activation by pristane, thus indicating that an intact CRE was necessary for pristane activation. In P+ cells, pristane repressed phosphodiesterase activity. However, protein kinase A was activated by pristane in P+ and P-cells. Taken together, these results indicated pristane induced novel changes in P+ cells that in turn may facilitate neoplastic transformation. PMID- 7999263 TI - Cytogenetic analysis of malignant skin tumors induced in chemically treated TG-AC transgenic mice. AB - TG.AC mice (which carry a v-Ha-ras transgene) rapidly develop papillomas in response to 12-O-tetradecanoylphorbol-13-acetate (TPA). Approximately 30% of the papillomas are associated with subsequent development of malignancies. Early passage spindle-shaped tumor cells arising from explant cultures of TPA-induced tumors in TG.AC mice were tumorigenic when transplanted to syngeneic recipients. The v-Ha-ras transgene in the transplanted tumors was expressed at a high level. To identify possible genetic changes associated with the development of malignant tumors, explanted cells were cultured in vitro and assessed for karyotypic changes between the second and third passages by analyzing G-banded metaphase chromosomes. For comparison, skin malignancies were induced in nontransgenic FVB/N mice (parent strain) by 7,12-dimethylbenz[a]anthracene (DMBA) initiation and TPA promotion, and their G-banded metaphase chromosomes were analyzed. Trisomy (in at least 50% of about 30 metaphases) of chromosome 15 (in five of 15 tumors) and chromosome 6 (four of 15 tumors) was observed in TG.AC mice, independent of chemical treatment or tumor type. Of six tumors from DMBA/TPA treated FVB/N mice, three had trisomy 10 or 15 (or both), and two appeared normal. The absence of trisomy 7 is notable because c-Ha-ras maps to that chromosome. The absence of trisomy 7 in the six FVB/N DMBA/TPA-induced skin malignancies contrasts with DMBA/TPA-induced karyotypic effects in SENCAR mice. Expression of the v-Ha-ras transgene may have precluded the requirement for endogenous mutant ras and allelic imbalance involving chromosome 7 in TG.AC mice, but it could not have in FVB/N mice. These results suggest the possibility that the observed trisomies are consequential, rather than causal, events in the development of TG.AC or FVB/N skin malignancies. Molecular genetic analysis will be required to understand the changes associated with tumorigenesis in this transgenic line as well as in the parent mouse line. PMID- 7999264 TI - DNA recombination induced by aflatoxin B1 activated by cytochrome P450 1A enzymes. AB - Mutations in tumor suppressor genes are intricately associated with the etiology of neoplasia. Often, such mutations are followed by the loss of the second, functional alleles of tumor suppressor genes, a phenomenon known as loss of heterozygosity. Loss of heterozygosity may occur by different molecular mechanisms, including mitotic recombination, and it is conceivable that these molecular events are influenced by endogenous as well as exogenous factors. To test whether mitotic recombination is induced by certain carcinogens, we genetically engineered a Saccharomyces cerevisiae tester strain so that it metabolizes two important classes of carcinogens, polycyclic aromatic hydrocarbons and heterocyclic arylamines. This was accomplished by expressing human cDNA's coding for the cytochrome P450 (CYP) enzymes CYP1A1 or CYP1A2 in combination with NADPH-CYP oxidoreductase in a strain heterozygous for two mutations in the trp5 gene. Microsomes isolated from the transformed yeast strains activated various xenobiotics to powerful mutagens that were detected in the Ames test. Of these, the mycotoxin aflatoxin B1, when activated intracellularly in the strains containing either human CYP enzyme, significantly induced mitotic recombination. These results are discussed in light of possible mechanisms that are involved in aflatoxin B1-mediated hepatocarcinogenesis. Similarly, benzo[a]pyrene-trans-7,8-dihydrodiol and 3-amino-1-methyl-5H pyrido[4,3-b]indole were activated to recombinagenic products, whereas benzo[a]pyrene and 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline were negative in this assay. Our results argue that the constructed yeast strains may be a valuable tool for the investigation of drug-induced mitotic recombination. PMID- 7999265 TI - Frequent p53 mutation in mouse tumors induced by repeated beta-irradiation. AB - On examination of cDNA of the p53 gene in 65 murine tumors of the skin and bone produced by repeated exposure to a suprathreshold dose of 1-8 Gy of 90Sr-90Y beta radiation per exposure, we found 20 cases of mutation: 11 minute deletions (loss of 1-24 bp), including two cases possibly due to aberrant splicing; three insertions of 4-8 bp; and six base-pair substitutions, including four at CpG sites, three being identical changes at codon 122 (a p53 hot spot). All but one of these mutations were confined to the central region of the p53 gene. From frameshifts created by deletions and insertions, the minimum size of the mutant p53 proteins found in these tumors was estimated to be 55% of the intact size. Cells of 17 of 19 tested tumors with p53 mutation were positive for immunostaining of p53 proteins accumulated in the nuclei and so were clearly different from nonneoplastic cells. Ha-ras mutation was absent in these tumors, indicating that repeated beta-irradiation created a cell-growth stimulating effect similar to that of ras mutation. PMID- 7999266 TI - A review of triage and management of burns victims following a nuclear disaster. AB - The field of combined injury is relatively unfamiliar to burn surgeons. The mortality and morbidity of combined injury victims is higher than that of the injuries separately. The secondary consequences of radiation exposure, e.g. immunosuppression, infection, bleeding and fluid and electrolyte loss, significantly affects the management plan for burn victims. Increased work loads on medical personnel and the hospital further affects the management plan and outcome adversely. Based on previous experiences and experimental studies by various authors, a plan for management of burn victims in nuclear casualties is presented for effective utilization of available resources for overloaded burn centres in emergency situations. The proper recording of the experience of such situations is stressed. PMID- 7999268 TI - Haematology reports of routine blood films in patients with burns. AB - A retrospective pilot study of 99 peripheral blood films from 27 patients with burns is reported. Abnormalities of the granular leucocyte series were more common in the more extensive burns and usually preceded bacteriological evidence of wound pathogens or a clinical decision to take a blood culture. The evidence suggests that a prospective study is needed to determine the possible clinical value of reporting such granulocyte abnormalities. Abnormalities of the myelo monocytic and lymphocyte cell lines were sufficiently frequent to permit fundamental research of possible relevance not only to patients with burns but in other host responses such as in sepsis, malaria or AIDS. PMID- 7999267 TI - Post-traumatic activation of draining lymph node cells. II. Proliferative and phenotypic characteristics. AB - Proliferative and phenotypic characteristics of cells in regional lymph nodes that drain burn injury were examined in rats on day 3 postburn, i.e. at the time of maximal spontaneous proliferation and of interleukin-2 and accessory cytokine (IL-1 and IL-6) production. The importance of IL-1 in spontaneous proliferation of draining lymph node cells was demonstrated by stimulation of IL-2-driven proliferation by recombinant IL-1 in vitro and by susceptibility of unstimulated proliferation to anti-IL-1 antibodies, while requirements for IL-6 in draining lymph node cell proliferation were less pronounced. Cell surface phenotyping revealed a slightly increased percentage of CD25+ cells in the blast cell population of freshly isolated draining lymph node cells after injury, which increased further during cultivation. Enrichment in CD8+ cells on day 3 following burn injury was demonstrated, while no changes in total cell population and CD4+ cells was noted. This was however preceded by pronounced percentual decrease of total T cells and CD4+ cells and by increases of B cells and MHC class II+ cells on day 1 postburn. Inhibition of draining lymph node cell proliferation by anti MHC class II antibodies suggested that this proliferation was class II MHC dependent. The contribution of cell proliferation and/or cell influx to day 3 postburn draining lymph node cell activity is discussed. PMID- 7999270 TI - Beta-haemolytic streptococcal infections in burned patients. AB - Colonization of burn wounds by beta-haemolytic streptococci can lead to the loss of autografts. The present study investigated the beta-haemolytic streptococcal infections in burned patients treated in the Burns Centre of the Emergency Medical Institute 'N. I. Pirogov'. Sofia during a 12-month period (March 1991 March 1992). As many as 117 beta-haemolytic streptococcal strains were isolated in 114 burned patients (52 children and 62 adults). The distribution of the streptococcal strains according to their serogroup was 64 strains (54.7 per cent) group A; 34 strains (29.1 per cent) group B; nine strains (7.7 per cent) group G; five strains (4.25 per cent) group C and five other strains (4.25 per cent) group F. Antibiotic sensitivity tests demonstrated the presence of some differences among the serogroups, especially between groups A and B. The sources of the streptococcal infections were found in 26 (29.2 per cent) of the patients. Epidemiological relationships were established between the strains from one source and the wound swab. For the successful treatment of beta-haemolytic streptococcal infections in burns it is essential to bear in mind the role of non group A beta-haemolytic streptococci (45.3 per cent according to our study). PMID- 7999269 TI - Cytoskeletal actin: the influence of major burns on neutrophil structure and function. AB - It has been noted that major trauma and burns patients who survive beyond 48 h most frequently succumb to sepsis and multiple organ failure. Furthermore, such patients are usually markedly hypermetabolic and in negative nitrogen balance at the time of their demise. Along with many other systemic and immune dysfunctions, the polymorphonuclear white blood cells in this setting become functionally impaired. Given that the motile white blood cells contain significant proportions of the contractile protein, actin, we speculated that the leucocyte dysfunction might in part be related to the overall systemic catabolism of actin stores. Accordingly, this hypothesis was explored by comparing the functions and cytoskeletal structure of neutrophilic leucocytes from normal control adults and victims of fresh, major thermal injuries. On days 1 and 7 after a burn of > 25 per cent of total body surface area, peripheral blood was drawn from 10 patients (mean age 33 years, mean burn area 44.2 per cent), and seven unburned controls (mean age 35.2 years). Neutrophils isolated from these specimens were tested for stimulated chemotactic rate, efficacy of intracellular killing as determined by superoxide production rate, and the levels of soluble and insoluble intracellular actin. In addition, both light microscopy and scanning electron microscopy were used to visualize the actin cytoskeleton. The results indicated that both chemotactic rate (12 mu/min vs. 38 mu/min--P < 0.05) and superoxide production rate (9 vs 43 mumol/ml10E6 cells--P < 0.05), were significantly reduced in the burn patients by day 7.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7999271 TI - Agar well diffusion assay testing of bacterial susceptibility to various antimicrobials in concentrations non-toxic for human cells in culture. AB - Previously, we showed that microbial susceptibility to antimicrobials in concentrations non-toxic for human cells in culture could be tested using the wet disc topical antimicrobial assay. In this report, wet disc assay and agar well diffusion assay results were compared testing the susceptibility of Ps. aeruginosa isolates from burn patients to concentrations of Polymyxin B non-toxic for cultured cells. Both assays were performed on the same agar plates. No differences in results were observed. Further agar well diffusion assay testing showed that susceptibility/resistance could be demonstrated when testing several antimicrobials in concentrations non-toxic for cultured cells against a variety of bacteria isolated from burn patients. Therefore, the more familiar agar well diffusion as well as the wet disc assay can be used to test microbial susceptibility to these concentrations of antimicrobials. PMID- 7999272 TI - Similar ectopic expression of ICAM-1 and HLA class II molecules in hypertrophic scars following thermal injury. AB - In previous studies we have shown that HLA Class II antigens are expressed by keratinocytes and fibroblasts in hypertrophic scars. Because of the potential role of immunological events in the pathogenesis of hypertrophic scars, in the present study we have tested hypertrophic scars for the expression of intercellular adhesion molecule-1 (ICAM-1), a molecule which plays an important role in immunological phenomena. Immunoperoxidase staining with anti-ICAM-1 MoAb of 10 hypertrophic scar samples detected this molecule on epidermal keratinocytes and on about 30 per cent of fibroblasts at the site of lymphoid infiltration. The expression of ICAM-1 in hypertrophic scars was similar to that of HLA Class II antigens. Since the concomitant expression of ICAM-1 and HLA Class II by keratinocytes is known to enhance their antigen-presenting properties, the present results support the possibility that immunological events play a role in the disruption of the normal processes of wound healing and tissue remodelling which result in hypertrophic scars. PMID- 7999273 TI - Respiratory distress secondary to scalds in children. AB - Respiratory distress secondary to scalds in children is rare. We report 13 children (six girls and seven boys) with a mean age of 19 months who sustained this injury, who were admitted to a major referral hospital during a 5.5-year period. Associated scalds usually to the face were always present and the mean total burn surface area (TBSA) was 14.4 per cent (range 3-30 per cent). Stridor was the most common presenting symptom with a variable time of onset. Bronchoscopy was performed in 11 children and in nine the injury was confined to the supraglottic area. Five children were treated with epinephrine nebulization and the symptoms resolved in 3-4 days, one child had a prophylactic tracheostomy. Seven children required intubation and ventilation. Three children died, two of whom sustained burns to both the upper and lower respiratory tract. Respiratory distress secondary to scalds may not be recognized or the progressive nature of the injury not appreciated. In three-quarters of our patients the injury was confined mainly to above the glottis. Children with inspiratory stridor can be managed with epinephrine nebulization but more marked respiratory distress requires intubation and ventilation. Mortality was due to direct thermal injury to the respiratory tract and secondary bronchopneumonia. PMID- 7999274 TI - Management of postburn contracture of the neck. AB - Five hundred and sixty-two patients with postburn contractures were treated by a plastic surgeon in the Central Hospital of the capital city Lusaka. There were 37 patients with neck contractures of whom 18 were classified as major, all but two were burned by fire and two-thirds were female. Release of contracture and excision of scar tissue followed by surface cover with skin grafting was the mainstay of treatment and was carried out in 31 of 37 patients. Careful perioperative management and the basics of plastic surgery such as skin grafting are within the competence of many general surgeons. Because burn contractures are common in the developing world, it is recommended that plastic surgery be included in the training of general surgeons and that selected cases be managed by them. The more complex cases should be referred to a plastic surgery centre. PMID- 7999275 TI - An audit of non-accidental injury in burned children. AB - The incidence of non-accidental injury in burned children and the repeat injury rate following non-accidental injury is very high according to some reports. A retrospective follow-up review was undertaken for all patients admitted to the Plymouth Paediatric Burns Unit over a 47-month period. Hospital records, general practitioners' records and the Social Services Department were used to gain follow-up information. The incidence of confirmed abuse was about 3 per cent and this included intentional injury as well as other forms of abuse such as neglect. The repeat injury rate was very low indeed. These figures are very much lower than many of the published figures. This may be due to differences in the definition of non-accidental injury, differences in the population make-up or simply that a burn injury is a relatively uncommon form of non-accidental injury in Devon and Cornwall. PMID- 7999276 TI - Early tangential excision and skin grafting as a routine method of burn wound management: an experience from a developing country. AB - This study assessed the feasibility of performing early tangential excision and skin grafting for burn wounds 'routinely' in a developing country. An analysis of mortality, morbidity and hospital stay was carried out for 90 burns patients with deep partial skin loss burns out of 202 admissions, who underwent 'early' tangential excision and skin grafting. Overall survival rate was 86.5 per cent. Children below 14 years of age with burns < or = 40 per cent TBSA (total body surface area) had no mortality, 93.5 per cent of adult patients with burns < or = 60 per cent TBSA survived in contrast to those with burns of > 60 TBSA per cent who all died. Morbidity for contractures and hypertrophic scars was nil to minimal. The mean hospital stay for adult patients with major burns was 30 days, with minor burns it was 18.7 days. We conclude that in developing countries, early tangential excision and skin grafting can and should be done routinely for all minor burns and for the major burns who are admitted to a well-equipped burns centre, but not for very 'extensive burns', until biological skin substitutes are more readily available. PMID- 7999278 TI - Burn care facilities in various European countries. PMID- 7999277 TI - Femoral arterial catheterization in paediatric burn patients. AB - Despite the obvious drawbacks associated with prolonged arterial cannulation, arterial catheters are frequently required in paediatric burn patients with respiratory failure to facilitate monitoring of oxygenation, ventilation and blood pressure, and to allow for the painless performance of phlebotomy. Burn patients with respiratory failure frequently require prolonged arterial catheterization, often for more than 72 h, and many of their cannulation sites are burned. We report our favourable 3-year experience with 81 femoral arterial catheters in 36 paediatric burn patients. When small diameter pressure monitoring catheters are used, femoral cannulation sites are associated with a low rate of mechanical and infectious complications. PMID- 7999279 TI - Erythema ab igne--a neglected entity? AB - The author describes two patients with erythema ab igne, a condition which used to be common before the introduction of central heating. Sporadic examples of the condition are still seen and treated. PMID- 7999280 TI - Preliminary report of the clinical use of cultured allogeneic keratinocytes. AB - Three case reports are used to show that the recently introduced skin culture technology has been mastered to the extent that three patients with deep burns covering 50 per cent and more of the body surface area survived. PMID- 7999281 TI - Trichosporon beigelii septicaemia in a burn patient. AB - A patient with Trichosporon beigelii sepsis secondary to a 31 per cent burn is reported. Good results were obtained by treatment with amphotericin B. No other reports of septicaemia due this organism in burn patients have been found by us, although the organism has been reported as a cause of sepsis in cancer patients. PMID- 7999282 TI - Fatal inhalation injury following an industrial accident involving acetic anhydride. AB - A 22-year-old man sustained 35 per cent burns to his skin and an inhalation injury in an industrial accident involving acetic anhydride. Although the skin burns healed following irrigation and conservative treatment, the inhalation injury proved fatal. PMID- 7999283 TI - Skin and extremity loss in meningococcal septicaemia treated in a burn unit. AB - Meningococcal septicaemia is a severe systemic illness which has an overall mortality of 15 per cent. It differs from meningococcal meningitis in clinical presentation, treatment, complications and prognosis. Skin and extremity loss are particular problems seen in meningococcal septicaemia. As critical care improves more patients are being seen with these complications. We report two patients in which these complications are demonstrated. Both patients underwent multiple autogenic and allogenic skin grafting procedures for skin loss. Apparently necrotic extremities were initially treated conservatively, with good results. The total area of necrotic tissue reduced dramatically with this treatment. Despite this, however, one patient required a Syme amputation, in the other, two toes on the affected foot separated painlessly at the metatarsophalangeal joint. We also discuss some of the pathophysiology behind skin necrosis. A popular view at present is that endotoxin from the cell wall of Neisseria meningiditis initiates the release of vasoactive cytokines by the host. High levels of interleukin-1 and interleukin-6 have been associated with a greater likelihood of fatality. PMID- 7999284 TI - An ECG electrode using a long 23G needle in burn patients. PMID- 7999285 TI - Easy way to prepare microskin grafts. PMID- 7999287 TI - Effectiveness of sealed dental prophylaxis angles inoculated with Bacillus stearothermophilus in preventing leakage. AB - It was the purpose of this in vitro investigation to evaluate the effectiveness of several brands of sealed, reusable prophylaxis angles to keep internal materials within the internal portions of the head of the prophylaxis angle, and not allowing contaminates to leak out. Three brands of sealed, reusable dental prophylaxis angles were autoclaved and then taken apart under a biocontainment flow hood. Testing conditions were designed to prevent a "worst case scenario" by inoculating dental prophylaxis angles with 10(6) of the heat resistant spores of Bacillus stearothermophilus and 20% bovine serum albumin to simulate the presence of human serum. The concentration of Bacillus stearothermophilus spores was verified before testing procedures were initiated. The internal portions of the sterile prophylaxis angles were inoculated with a 1:1 mixture of the Bacillus stearothermophilus spores and bovine serum albumin, at a concentration of 1.15 x 10(6) spores/inoculation. The prophylaxis angles were reassembled under sterile conditions, and a sterile rubber cup was inserted into each of the prophylaxis angles. The prophylaxis angles were attached to a sterile dental handpiece and then submerged in a 50 ml tube containing sterile trypticase soy broth and run at 3000 rpm for 30 seconds. The tube of medium was incubated for 7 days. No growth of Bacillus stearothermophilus spores could be cultured from one of the brands of prophylaxis angles at any time during the incubation period. The other two brands of prophylaxis angles did produce some leakage of the Bacillus stearothermophilus spores. PMID- 7999286 TI - Inactivation of viruses by glycerol as used in allograft skin preservation. PMID- 7999288 TI - A comparative evaluation of the percent acceptable end-rounded bristles: Butler G.U.M., Colgate Plus, Crest Complete, and Reach. AB - Many researchers have concluded that end-rounded toothbrush bristles reduce the potential of soft tissue trauma. Toothbrushes with a rippled-bristle pattern have been shown to more effectively remove dental plaque from interproximal surfaces than flat-trimmed toothbrushes. Unfortunately, many attempts to utilize rippled bristle toothbrushes are fraught with difficulty due to poor end-rounding of these bristles in the traditional manufacturing process. In this study, the proportion of acceptably end-rounded bristles has been compared for a rippled bristle design toothbrush (Crest Complete), a traditional flat-trimmed brush (Colgate Plus), a bi-level brush (Reach), and a domeshaped brush (Butler G.U.M. 411). Toothbrush bristles were examined using a stereomicroscope by a grader blind to brush type, and bristle end-rounding was evaluated based on the Silverstone and Featherstone scale used previously in the literature. The results were tabulated for the percent of bristles with acceptable grades, summed, and averaged for five random bristles per tuft, five random tufts per brush, for 30 brushes of each type. Bristles in the Crest Complete toothbrush demonstrated 96.5% acceptable end-rounding. These results were significantly different (p = 0.0001) from those found in the other brushes tested: 34.3% (Reach), 16.1% (Colgate Plus), and 14.0% (Butler G.U.M.) acceptable end-rounding was observed. These results demonstrate that the newly designed rippled-bristle brush (Crest Complete) exhibits excellent bristle end-rounding. PMID- 7999289 TI - Two long-term clinical studies comparing the plaque removal and gingivitis reduction efficacy of the Oral-B Advantage Plaque Remover to five manual toothbrushes. AB - Two long-term studies were conducted to evaluate the therapeutic efficacy of five manual toothbrushes compared to the Oral-B Advantage Plaque Remover measuring plaque removal and gingivitis/bleeding reduction. Both studies were carried out under the same protocol and utilized the same examiners. In Study 1, the Oral-B Advantage Plaque Remover was compared to the Crest Complete and Colgate Precision toothbrushes. In Study 2, the Oral-B Advantage Plaque Remover was compared to the Reach Advanced Design, Colgate Plus and Jordan Exact toothbrushes. A total of 109 and 121 male and female subjects who met the inclusion and exclusion criteria completed Study 1 and Study 2, respectively. Subjects were initially screened for dental plaque eligibility having abstained from oral hygiene for a prior 24-hour period. Subjects were randomly assigned to one of the balanced groups and received a professional prophylaxis to reduce plaque scores. Subjects were then scheduled to return 4 weeks and 8 weeks later, having again abstained from all oral hygiene procedures for a prior period of 24 hours. At each visit, each subject was evaluated for plaque, gingivitis and bleeding. Upon completion of the study, the data were subjected to statistical analysis. The results of both studies are summarized as follows: The Oral-B Advantage Plaque Remover was significantly more effective than the Crest Complete, Colgate Precision, Colgate Plus and Jordan Exact toothbrushes in whole mouth plaque removal (p < 0.05), and vs. all brushes tested in gingivitis reduction (p < 0.01) and in reducing gingival bleeding (p < 0.001). PMID- 7999290 TI - Alcohol-containing mouthwashes: effect on composite hardness. AB - This study evaluated the effects of alcohol-containing mouthwashes on composite resin hardness. Eighty hybrid composite discs were fabricated and divided into eight equal groups: Listerine, Scope, Viadent, Plax, Lavoris, Clear Choice, and Rembrandt Mouth Refreshing Rinse. Water acted as a control. All of the discs were immersed by group in their respective liquids for two minutes a day over a period of six months. Disc hardness was measured six times at the center and periphery using a Barcol impressor. The baseline values were taken for each disc and compared to the test values at the end of six months. The results of the study indicate that the alcohol content in mouthwashes can affect composite hardness. This softening affect can be directly related to the percentage of alcohol in the mouthwash. PMID- 7999291 TI - The effect of Parodontax dentifrice on gingival bleeding. AB - In this study on twenty-two adult subjects, the effectiveness of Parodontax dentifrice was compared to a control dentifrice on gingival bleeding parameters. The periodontal probe bleeding index of Ainamo and Bay, modified to evaluate slight and moderate bleeding, was used to evaluate efficacy. There was no significant difference between the two groups at baseline. After four weeks, Parodontax dentifrice produced a significant decrease (p < 0.01) in bleeding on probing compared both to baseline (p < 0.01) and to the control group (p < 0.05), and an increase (p < 0.05) in the number of sites with no bleeding compared to the control dentifrice. The control had no significant decrease in bleeding on probing from baseline to four weeks. The number of bleeding sites were significantly reduced in the Parodontax dentifrice group from baseline to week four (p < 0.001), and there was no significant statistical change in the number of bleeding sites for the control group. The Parodontax dentifrice group bleeding sites at four weeks were significantly lower than the control group (p < 0.05). PMID- 7999292 TI - [Diabetes in Mexico: what does the National Health Survey tell us?]. AB - The purpose of this monograph is to describe the sociodemographic and health characteristics of individuals who identified themselves as diabetics (through self-notification) in a national health survey that was conducted in Mexico in 1988 and in which information about more than 200,000 persons was collected by interviewing an adult member of each household. Of the population surveyed, 1.2% stated being diabetic, and it was noted that the frequency of the disease increased with age and socioeconomic status and that it was 30% higher in women than in men. Diabetics had higher notification rates for hypertension, heart disease, and blindness than the rest of the population. Twenty percent of diabetic patients and 12% of nondiabetic individuals smoked. People with diabetes consulted physicians twice as often as nondiabetics and their chances of being hospitalized were four times higher. At the end we discuss the limitations and possible biases of self-notification as a method for detecting diabetics. Finally we conclude that diabetes is an important health problem in Mexico and that it warrants more attention from epidemiologists and other public health specialists. PMID- 7999293 TI - [Surveillance of HIV seroprevalence in adults and children with and without tuberculosis in a hospital of Haiti]. PMID- 7999294 TI - Sleep and dynamic stabilization of neural circuitry: a review and synthesis. AB - A common mechanism is advanced for the lengthy stabilization of neural circuitry encoding information of both hereditary and experimental origin. Stabilization is proposed to occur through the following means and interrelationships. Synaptic function is intrinsically plastic because of greatly restricted entry of essential, relatively short-lived molecules into synaptic terminals. Alterations that accompany synaptic transmission transiently facilitate this entry ("facilitated entry"). Synaptic efficacy is enhanced as the concentration of these molecules increases following a transmission event but subsequently declines if depletion of the molecules occurs without commensurate replacement. Accordingly, if lengthy persistence of information encoded by enhancements of synaptic efficacy is to be achieved, the enhancements must be reinforced repeatedly by synaptic transmission ("dynamic stabilization"). Synapses of circuits not in frequent functional use are thought to be dynamically stabilized by spontaneous, internally generated, "non-utilitarian" excitations occurring primarily during rest or sleep. In species with complex, highly developed brains, requirements for dynamic stabilization of infrequently used circuits apparently cannot be met during rest, a restriction that may underlie the origin of sleep. Dynamic stabilization of infrequently used motor circuits of endotherms appears to occur predominantly during REM sleep. PMID- 7999295 TI - Retention and relearning of spatial delayed alternation in rats after ablation of the prefrontal or total non-prefrontal isocortex. AB - In the present study we addressed the question whether, within the isocortex, the prefrontal area of the rat is uniquely involved in mediation of delayed alternation. In one group of rats the dorsolateral isocortex, from the dorsomedial shoulder to the dorsal lip of the rhinal sulcus was removed bilaterally in a single surgical session. In these rats delayed alternation in a T-maze was significantly less impaired than in rats with one stage bilateral removal of the medial prefrontal cortex. The prefrontal cortex seems not to depend crucially on isocortical input for its medication of delayed alternation. PMID- 7999296 TI - Ultrasonic vocalization induced by intracerebral carbachol in rats: localization and a dose-response study. AB - It has been recently demonstrated that application of a cholinergic agonist, carbachol, into the anterior hypothalamic-preoptic area in the rat can induce 22 kHz ultrasonic vocalization. Functional mapping of the response in the forebrain and diencephalic regions of the rat brain, as well as the relationship between the dose of carbachol and the multi-parameter recording of vocalization are analyzed in the present study. Direct pressure injection of carbachol into the brain of adapted rats induced a 22 kHz ultrasonic vocalization from a limited region of the anterior hypothalamic-preoptic area and the vicinity of the septum. The response was antagonized by a local pretreatment with atropine and could not be induced by injections of saline vehicle or by handling. Measurements of summed duration of individual calls and response duration showed a typical dose-response relationship for 32-fold range of carbachol doses with ED50 = 0.73 micrograms (4.0 nmol). The increasing dosage of carbachol did not influence the frequency of emitted ultrasounds. On the other hand, the sound intensity increased and the bandwidth decreased with the increasing dosage of carbachol. The mean duration of single calls was also significantly decreased with the carbachol dosage. However, higher doses of carbachol decreased the number of short calls (100-150 ms) but increased the number of longer calls (300-400 ms). The duration of individual calls appeared to be a sensitive index of the response intensity. The results suggest that the cholinergic input into the mediobasal forebrain may play a physiological role in initiating and emitting the 22 kHz ultrasonic vocalization in rats, and that changes in call duration, intensity and bandwidth may be involved in conveying information for conspecifics. PMID- 7999297 TI - Effects of intracranial injections of scopolamine on olfactory conditioning retrieval in the honeybee. AB - The role of the cholinergic system on learning abilities and memory performance has been investigated in the honeybee. The behavioural experiment was the olfactory conditioning of the proboscis extension reflex, elicited by an antennal sucrose stimulation. Intracranial scopolamine (0.5 mg/kg) or saline injections (0.25 microliter) were given at different times before or after a one trial learning session in order to interfere with acquisition of information, storage or recall processes. Neither scopolamine injections, ranging from 20 min to 5 min prior to the acquisition task, nor post-trial drug injections given in the same time-window, impaired the retention performance measured one hour after conditioning. Scopolamine injected 20 min after a learning session induced a time dependent decrease of information retrieval, as was seen in retention testing performed from 5 min to one hour after injection. Then, the amnestic effect of intracranial scopolamine injection seems to be related to a specific and temporary inhibition of recall processes. We can conclude that, in the present task, muscarinic-like receptors are involved in information retrieval but not in acquisition or consolidation processes. PMID- 7999298 TI - The coordination and control of human creeping with increases in speed. AB - Changes were documented in the inter-limb and intra-limb timing of well trained adult males creeping at increasing speed on a motor-driven treadmill. A power function (y = axb) showed a good fit to hand and foot stride and support duration (y) and speed (x), a finding that parallels the changes expected in normal upright walking. Similarly, limbs of the same girdle maintained a half-cycle phase lag as speed increased. Swing duration, however, showed cyclical changes with increasing speed, a phenomenon not previously reported either for quadrupedal gait or normal upright gait. Ipsilateral hands and feet abruptly changed their phase-lags at a constant percentage of maximum speed in a manner similar to gait transitions observed in quadrupedal species. Explanations for these transitions were suggested, such as physical constraints on the speed of limb movement and the organism's biomechanical adaptation to increased metabolic energy expenditure. PMID- 7999299 TI - Components of weasel and fox odors elicit fast wave bursts in the dentate gyrus of rats. AB - Previous work has shown that olfactory stimulation with toluene, xylene and other organic solvents elicits a burst of 15-30 Hz fast waves in the dentate gyrus of male rats. Other odorous substances including food, rat vaginal secretions and rat excrement were much less effective. In the present study we confirm that water, ammonia, rat food, rat cage litter and the presence of a conspecific did not reliably elicit dentate fast wave responses but that toluene and methyl methacrylate were very effective. We further show that both 2-propylthietane, which is a component of weasel gland secretions, and trimethyl thiazoline, an ingredient of fox droppings, elicited dentate fast waves as effectively as toluene and methyl methacrylate and that putrescine, cadaverine, butyric acid, caproic acid and indole were ineffective by comparison. Similarly, orally administered solutions of acetic acid, quinine, sodium chloride and sucrose were ineffective. These findings raise the possibility that the dentate fast waves elicited in the rat may be part of a cerebral response to the odor of a potential predator, such as the weasel or fox. PMID- 7999300 TI - Morphological and behavioural effects of granule cell degeneration induced by intrahippocampal fluid injections in intact and fimbria-fornix lesioned rats. AB - This study was aimed at determining whether granule cell degeneration induced by intragyral injections of a neutral fluid (0.9% NaCl with 0.6% glucose, pH 7.0, 2 sites per hippocampus, 2 microliters/site, 1 microliter/min) produced behavioural deficits in rats which, 2 weeks prior to the injections had received either fimbria-fornix lesions or sham-operations. In both sham-operated and lesioned rats, we found such injections to induce a comparable, topographically-limited loss of granule cells in the dorsal leaf of the dentate gyrus and, in the close vicinity of the degeneration area, a severe shrinkage of the molecular layer with concomitant morphological reorganizations (e.g. acetylcholinesterase reaction products were distributed uniformly throughout the molecular layers of sham operated rats). While the fimbria-fornix lesions produced classically reported behavioural deficits (hyperactivity in both a familiar and an unfamiliar environment. reduced T-maze alternation rates and impaired radial-maze performance), we could not detect adversive effects of the granule cell degeneration on either of these variables in sham-operated and lesioned rats. Our data suggest that limited granule cell degeneration induced by intragyral fluid injections has no effect on locomotor activity, spontaneous alternation and spatial learning. Therefore, we may also infer that the granule cell damage observed after an intragyral implantation of a fetal neural cell suspension does probably not account for the behavioural deficits which, in some experiments, have been found in fimbria-fornix lesioned rats bearing intragyral cell suspension grafts. PMID- 7999301 TI - Performance (re-acquisition) of a water-maze task by adult meadow voles: effects of age of initial task acquisition and in utero environment (litter sex-ratio). AB - Previous research in this laboratory has shown that preweaning and postweaning juvenile meadow voles, Microtus pennsylvanicus, can acquire a spatial task, the Morris water-maze task. The present study examined the influence of age of juvenile acquisition ("before weaning" (BW; Day 10 and 15 after birth) and "after weaning" (AW; Day 20 and 25 after birth)) of a spatial task on subsequent re acquisition of the same hidden-platform spatial water-maze task. This study also compared sex differences and litter sex-ratio effects on reacquisition performance. Fifteen litters of adults were re-tested in the same water maze 6 weeks after being initially tested as juveniles. All analyses were conducted using a covariate that removed the group differences in the original task performance. Adult voles from female-biased litters, that had previously learned the task at an older juvenile age (AW), reacquired the same task faster than adults that had previously learned the task at a younger juvenile age (BW). In the adult BW group there was also a significant litter sex-ratio effect such that voles born into a female-biased litter re-acquired the task more slowly than did voles born into a male-biased litter. There were no significant sex or litter sex ratio effects on spatial learning in the AW group. These results show that adult meadow voles can require a spatial task more quickly if they initially learned the task at an older juvenile age, suggestive of a period of infantile amnesia. In addition, these results indicate that the litter sex-ratio can affect adult spatial performance, suggesting that the relative amount of androgens in utero may influence the development of sexually-dimorphic spatial ability in adulthood. PMID- 7999303 TI - Analysis of two measures of paw preference in a large population of inbred mice. AB - Two measures of lateralized forelimb usage, the Collins paw preference test and the Lateral Paw Preference test (LPP), were tested in 693 mice of 29 inbred strains and F1 crosses, and 2 embryo transfer groups. These strains included NZB, SM, and the NXSM recombinant inbred (RI) strains; RF and the NXRF RI strains; BXSB and the Y-consomic BXSB-Yaa+; DBA/2 and F1s of DBA/2 and BXSB and BXSB-Yaa; and NZB x NZW F1s. The findings indicated that (1) the Collins and LPP tests were independent in terms of direction of lateralization, (2) there were significant population biases of 60.96% rightward on the LPP test, and 54.39% leftward on the Collins test, (3) there were significant strain differences on measures of absolute asymmetry on both tests, (4) there were strain differences for direction of asymmetry on the Collins test, but not on LPP, (5) on the basis of the NXSM RI strains, 3 genetic loci contribute to strength of laterality on the LPP test, and (6) there was a strong correlation among strain means for strength of lateralization on the two tests. These results extend previous findings on the strength and direction of laterality, showing that two independent systems for direction of laterality may depend on the same mechanism for magnitude, and establish that multiple factors of handedness, previously identified in humans and other primates, also exist in mice. PMID- 7999302 TI - Quinolinic acid lesion of the rat entorhinal cortex pars medialis produces selective amnesia in allocentric working memory (WM), but not in egocentric WM. AB - The functional role of the entorhinal cortex pars medialis in memory formation was investigated by lesioning this area with quinolinic acid, a selective agonist of the NMDA-subtype of glutamate receptors which has neurotoxic properties. With this technique "en passant" axons are spared and only neurons of the target area are destroyed. The effects of this lesion on learning abilities in the 8-arm maze were tested. Rats in the lesion group showed different exploring behavior: animals did not visit all arms, and previously visited arms were reentered. When orienting themselves on distal cues (allocentric tests) the animals showed working memory (WM) deficits and reduced speed of acquisition of reference memory (RM). When changing arms that were baited, the test group had difficulties learning the new task. Performance decreased after introduction of a delay. However, when orienting themselves on proprioceptive cues (egocentric tests), no deficits in memory formation were detectable. Animals appeared hypomotoric in all tests. PMID- 7999304 TI - Room light impairs sleep in the albino rat. AB - Since the rat is a nocturnal animal sleep experiments in this species are commonly performed during the light period of the 24-h light-dark (LD) cycle. To examine whether light itself affects sleep, chronically implanted albino rats were continuously recorded for a day under a 12-h light-12-h dark cycle (light intensity approx. 300 lx) and on the subsequent day in constant darkness (DD). In the absence of light, EEG slow-wave activity (0.75-4.0 Hz) in non-REM sleep and sleep continuity were significantly enhanced, while total sleep time and cortical temperature were not affected. The results show that in the albino rat room light impairs sleep by reducing its intensity and continuity. PMID- 7999305 TI - Direct osmotic stimulation of the hypothalamic paraventricular nucleus by microdialysis induces excessive grooming in the rat. AB - This study examined the effects of direct osmotic stimulation of the hypothalamic paraventricular nucleus (PVN) on grooming behavior of adult male rats. Animals chronically fitted with a microdialysis probe in the right PVN responded to dialysis with hypertonic (containing 1 M NaCl) artificial cerebrospinal fluid (aCSF) with grooming behavior (to approx. 500%, P < 0.01, ANOVA) and a significantly reduced time resting (to approx. 20%, P < 0.01, ANOVA), compared with controls which received either the same treatment in the right supraoptic nucleus or in which the PVN was dialyzed with isotonic (0.15 M NaCl) a CSF. These results indicate that direct osmotic stimulation of the PVN via microdialysis is able to trigger and to maintain excessive grooming activity in rats; the novel experimental approach used here provides the potential to investigate the involvement of endogenous, intracerebrally released substances in the grooming response. PMID- 7999306 TI - PrP in pathology and pathogenesis in scrapie-infected mice. AB - PrP accumulation in the brains of mice infected with scrapie takes several different forms: amyloid plaques, widespread accumulation in neuropile, and perineuronal deposits. PrP is also sometimes detected within microglia and in or around astrocytes. There are dramatic and reproducible differences between scrapie strains in the relative prominence of these changes and their distribution in the brain. Depending on the scrapie strain, PrP pathology is targeted precisely to particular brain areas, often showing a clear association with identifiable groups of neurons. These results suggest that PrP changes are primarily associated with neurons, and that different scrapie strains recognize and selectively replicate in different populations of neurons. Immunostaining at the ultrastructural level demonstrates an association of PrP with neurite plasmalemma, around amyloid plaques, and in areas of widespread neuropile and perineuronal accumulation. It is probable that PrP is encoded by the Sinc gene, which controls the incubation period of scrapie in mice. Studies using the intraocular infection route show that the Sinc gene controls the onset rather than the rate of replication, suggesting that PrP may be involved in cell-to-cell spread of infection. The accumulation of PrP at the surface of neurons is consistent with such a role. PMID- 7999307 TI - Inhibition of scrapie-associated PrP accumulation. Probing the role of glycosaminoglycans in amyloidogenesis. AB - Accumulation of an abnormal, protease-resistant form of an endogenous protein, PrP, is a characteristic feature of scrapie and related transmissible spongiform encephalopathies. This abnormal isoform is also present in the amyloid plaques that are often observed in these diseases. In mouse neuroblastoma cells persistently infected with scrapie, the abnormal protease-resistant isoform of PrP is derived from an operationally normal protease-sensitive precursor. Conversion of PrP to the protease-resistant state occurs either on the plasma membrane or along an endocytic pathway by an unknown mechanism. Inhibitors of protease-resistant PrP accumulation have been identified, and these include the amyloid-binding dye Congo red and certain sulfated glycans. The similarity of these compounds to sulfated glycosaminoglycans, which are components of all natural amyloids, has led to the hypothesis that the inhibitors act by competitively blocking an interaction between endogenous glycosaminoglycan(s) and PrP that is critical for amyloidogenic PrP accumulation. The proven prophylactic effect of these sulfated glycans in animal models of scrapie suggests that they represent a group of compounds that might interfere with the pathogenic formation of amyloid in a variety of diseases, such as Alzheimer's disease. PMID- 7999308 TI - 129/Ola mice carrying a null mutation in PrP that abolishes mRNA production are developmentally normal. AB - The neural membrane glycoprotein PrP is implicated in the pathogenesis of the transmissible spongiform encephalopathies; however, the normal function of PrP and its precise role in disease are not understood. Recently, gene targeting has been used to produce mice with neo/PrP fusion transcripts, but no detectable PrP protein in the brain (1). Here we report the use of a different targeting strategy, to produce inbred mice with a complete absence of both PrP protein and mRNA sequences. At 7 mo of age, these mice show no overt phenotypic abnormalities despite the normal high levels of expression of PrP during mouse development. The mice are being used in experiments designed to address the role of PrP in the pathogenesis of scrapie and the replication of infectivity. PMID- 7999309 TI - Scrapie strain infection in vitro induces changes in neuronal cells. AB - PC12 cells, in the presence of nerve growth factor (NGF), support replication of the mouse-derived scrapie strains 139A and ME7, with the former yielding 100-1000 fold higher levels of infectivity. Infectivity remained cell-associated and cells did not show any gross morphological alterations, although changes were observed by electron microscopy in the form of an increased number of lipid droplets in 139A-infected cultures. Analysis of phospholipid metabolism in 139A infected cells indicated that scrapie replication did not change the inositol phosphate levels, but did stimulate phosphoinositide synthesis. Replication was not detected in PC12 cells infected with either the hamster-derived 263K or rat derived 139R scrapie strains. Since scrapie-infected cultures did not exhibit cell death or any gross changes, any scrapie-induced effects would probably be manifested in nonvital cellular functions. When compared to controls, infection with the 139A scrapie strain resulted in decreased activity of the cholinergic pathway-related enzymes, as well as the GABA synthetic pathway; however, the adrenergic pathway was unaffected by scrapie infection. The effects of the 139A scrapie strain on the cholinergic system appeared to be dose-dependent and were first detected prior to the detection of scrapie agent replication in these cells. No neurotransmitter-related enzymatic changes were detected in 263K- or 139R-infected PC12 cells. The enzymatic changes observed in ME7-infected PC12 cells and in Chandler agent-infected mouse neuroblastoma cells suggest that the significant changes in neurotransmitter levels in cultures exhibiting low infectivity titers must involve factors other than, but not excluding, replication of the agent. The role of additional factors is also suggested in studies of protein kinase C activity in 139A- and 139R-infected PC12 cells. These studies emphasize the value of the PC12 cell model system in examining the scrapie strain-host cell interaction and, in addition, support the concept of variation among scrapie strains. PMID- 7999310 TI - The presence of HTLV-I proviral DNA in the central nervous system of patients with HTLV-I-associated myelopathy/tropical spastic paraparesis. AB - Human T-lymphotropic virus type 1 (HTLV-I) is a pathogenic retrovirus associated with a chronic progressive myelopathy, termed HTLV-I-associated myelopathy (HAM)/tropical spastic paraparesis (TSP), as well as adult T-cell leukemia (ATL). A chronic inflammatory process has been implicated in HAM/TSP by a pathological study, but the exact mechanism still remains unknown. To understand better the complex mechanism of disease induction by HTLV-I, I studied the spreading pattern of HTLV-I in both peripheral blood mononuclear cells (PBMNCs) and central nervous system (CNS) tissues in patients with HAM/TSP using a quantitative polymerase chain reaction (PCR) method. My results indicated the primary event to be the efficient replication of HTLV-I in vivo, whereas HTLV-I is likely to be present in the constituent cells of the CNS in addition to the infiltrating mononuclear cells. PMID- 7999311 TI - HTLV-I, infective dermatitis, and tropical spastic paraparesis. AB - Since human T-cell lymphotropic virus (HTLV-I) was identified in 1980 as causing human disease, it has been etiologically associated with adult T-cell lymphoma/leukemia (ATL) and tropical spastic paraparesis (TSP). More recently, several new diseases have been reported in association with this virus, including infective dermatitis of Jamaican children, which we reported in 1990. Studies on infective dermatitis have shown that these children have abnormalities of immune function, and some develop other HTLV-I associated disorders, including TSP. This paper reviews the work done on infective dermatitis to date, and explores the association with TSP. PMID- 7999312 TI - The myeloneuropathies of Jamaica. AB - This article summarizes the present state of knowledge of TSP/HAM as it is seen in Jamaica. It reviews the historical and clinical aspects of the disease, and shows how the discovery of HTLV-I has generated research in several countries and contributed to a better understanding of the disease. It highlights the need for continued collaboration between basic scientists and clinical neurologists in order that the dilemmas relating to therapy and pathogenicity may be successfully addressed. PMID- 7999314 TI - Tropical spastic paraparesis/HTLV-I associated myelopathy. Etiology and clinical spectrum. AB - In 1985 we had the first indication that human T-cell lymphotropic virus (HTLV-I) was the possible etiological agent of a chronic myelopathy that seemed to be peculiar to the tropics and that is now known as endemic tropical spastic paraparesis (TSP). IgG antibodies to HTLV-I were found in serum and cerebrospinal fluid of patients from Jamaica, Colombia, Martinique, and shortly after in southern Japan, where the disease is called HTLV-I-associated myelopathy (HAM). The HTLV-I seropositivity was first determined by enzyme-linked immunoassay and confirmed by western immunoblot and in the cerebrospinal fluid specific IgG oligoclonal bands to HTLV-I were found in cerebrospinal fluid and not in serum. These laboratory findings indicated that HTLV-I could be neuropathogenic and for the first time a single etiological agent was identified in patients from different countries. Thus, in less than a decade a century of research and speculation was seemingly resolved when this disease, which was thought to occur only in blacks of poor socioeconomic status in tropical countries, was shown to occur in all ethnic groups of varying socioeconomic status in temperate, subtropical, and tropical climates. PMID- 7999316 TI - Neurodegenerative diseases. Part II: transmissible neurodegenerative disorders. Proceedings of a symposium. Ocho Rios, Jamaica, February 28-March 5, 1993. PMID- 7999313 TI - Genetic and phylogenetic analyses of human T-cell lymphotropic virus type I variants from Melanesians with and without spastic myelopathy. AB - Molecular variants of human T-cell lymphotropic virus type I (HTLV-I) have been isolated recently from lifelong residents of remote Melanesian populations, including a Solomon Islander with tropical spastic paraparesis/HTLV-I-associated myelopathy (TSP/HAM) or HTLV-I myeloneuropathy. To clarify the genetic heterogeneity and molecular epidemiology of disease-associated strains of HTLV-I, we enzymatically amplified, then directly sequenced representative regions of the gag, pol, env, and pX genes of HTLV-I strains from Melanesians with and without TSP/HAM, and aligned and compared these sequences with those of HTLV-I strains from patients with TSP/HAM or adult T-cell leukemia/lymphoma and from asymptomatic carriers from widely separated and culturally disparate populations. Overall, the HTLV-I variant from the Solomon Islander with TSP/HAM, like HTLV-I strains from asymptomatically infected Melanesians, diverged by approx 7% from cosmopolitan HTLV-I strain. No disease-specific viral sequences were found. Gene phylogenies, as determined by the unweighted pair-group method of assortment and by the maximum parsimony method, indicated that the Melanesian and cosmopolitan strains of HTLV-I have evolved along separate geographically dependent lineages, one comprised of HTLV-I strains from Papua New Guinea and the Solomon Islands, and the other composed of virus strains from Japan, India, the Caribbean, Polynesia, the Americas, and Africa. The total absence of nonhuman primates in Papua New Guinea and the Solomon Islands precludes any possibility that the Melanesian HTLV-I strains have evolved recently from the simian homolog of HTLV I. PMID- 7999317 TI - The "brave new world" of transmissible spongiform encephalopathy (infectious cerebral amyloidosis). AB - The story of transmissible human spongiform encephalopathy, from its origins to the present time, enjoys the commentary of a cast of characters from Shakespeare's imaginary island in The Tempest, with a brief visit to the real island of Tasmania for a bird's eye view of the prion, and some concluding thoughts about the current state of research in the netherworlds of molecular biology and physical chemistry. PMID- 7999318 TI - Molecular genetic studies of Creutzfeldt-Jakob disease. AB - Genetic study of over 200 cases of Creutzfeldt-Jakob disease (CJD), Gerstmann Straussler-Scheinker disease (GSS), fatal familial insomnia (FFI), and kuru have brought a reliable body of evidence that the familial forms of CJD and all known cases of GSS and FFI are linked to germline mutations in the coding region of the PRNP gene on chromosome 20, either point substitutions or expansion of the number of repeat units. No pathogenic mutations have so far been found in sporadic or infectious forms of CJD, although there are features of genetic predisposition in iatrogenic CJD and kuru. In FFI and familial CJD, clinically and pathologically distinct syndromes that are both linked to the 178Asp-->Asn substitution, phenotypic expression is dependent on a polymorphism at codon 129. Synthetic peptides homologous to several regions of PrP spontaneously form insoluble amyloid fibrils with unique morphological characteristics and polymerization tendencies. Peptides homologous to mutated regions of PrP exhibit enhanced fibrilogenic properties and, if mixed with the wild-type peptide, produce even more abundant and larger fibrous aggregates. A similar process in vivo may lead to amyloid accumulation and disease, and transmission of "baby fibrils" may induce disease in other hosts. PMID- 7999320 TI - Sensory functioning and intelligence in old age: a strong connection. AB - Relations among age, sensory functioning (i.e., visual and auditory acuity), and intelligence were examined in a heterogeneous, age-stratified sample of old and very old individuals (N = 156, M age = 84.9 years, age range = 70-103). Intelligence was assessed with 14 tests measuring 5 cognitive abilities (speed, reasoning, memory, knowledge, and fluency). Together, visual and auditory acuity accounted for 49.2% of the total and 93.1% of the age-related reliable variance in intelligence. The data were consistent with structural models in which age differences in intelligence, including speed, are completely mediated by differences in vision and hearing. Results suggest that sensory functioning is a strong late-life predictor of individual differences in intellectual functioning. Explanations are discussed, including the possibility that visual and sensory acuity are indicators of the physiological integrity of the aging brain (common cause hypothesis). PMID- 7999315 TI - HIV-related neuronal injury. Potential therapeutic intervention with calcium channel antagonists and NMDA antagonists. AB - Perhaps as many as 25-50% of adult patients and children with acquired immunodeficiency syndrome (AIDS) eventually suffer from neurological manifestations, including dysfunction of cognition, movement, and sensation. How can human immunodeficiency virus type 1 (HIV-1) result in neuronal damage if neurons themselves are for all intents and purposes not infected by the virus? This article reviews a series of experiments leading to a hypothesis that accounts at least in part for the neurotoxicity observed in the brains of AIDS patients. There is growing support for the existence of HIV- or immune-related toxins that lead indirectly to the injury or demise of neurons via a potentially complex web of interactions among macrophages (or microglia), astrocytes, and neurons. HIV-infected monocytoid cells (macrophages, microglia, or monocytes), after interacting with astrocytes, secrete eicosanoids, i.e., arachidonic acid and its metabolites, including platelet-activating factor. Macrophages activated by HIV-1 envelope protein gp120 also appear to release arachidonic acid and its metabolites. In addition, interferon-gamma (IFN-gamma) stimulation of macrophages induces release of the glutamate-like agonist, quinolinate. Furthermore, HIV infected macrophage production of cytokines, including TNF-alpha and IL1-beta, contributes to astrogliosis. A final common pathway for neuronal susceptibility appears to be operative, similar to that observed in stroke, trauma, epilepsy, neuropathic pain, and several neurodegenerative diseases, possibly including Huntington's disease, Parkinson's disease, and amyotrophic lateral sclerosis. This mechanism involves the activation of voltage-dependent Ca2+ channels and N methyl-D-aspartate (NMDA) receptor-operated channels, and, therefore, offers hope for future pharmacological intervention. This article focuses on clinically tolerated calcium channel antagonists and NMDA antagonists with the potential for trials in humans with AIDS dementia in the near future. PMID- 7999319 TI - A novel mechanism of phenotypic heterogeneity demonstrated by the effect of a polymorphism on a pathogenic mutation in the PRNP (prion protein gene). AB - Fatal familial insomnia (FFI) is a subacute dementing illness originally described in 1986. The phenotypic characteristics of this disease include progressive untreatable insomnia, dysautonomia, endocrine and motor disorders, preferential hypometabolism in the thalamus as determined by PET scanning, and selective thalamic atrophy. These characteristics readily distinguish FFI from other previously described neurodegenerative conditions. Recently, FFI was shown to be linked to a mutation in the prion protein gene (PRNP) at codon 178, which results in the substitution of asparagine for aspartic acid. As such, FFI represents the most recent addition to the growing family of prion protein related diseases. The mutation that results in FFI had previously been linked to a subtype of familial Creutzfeld-Jakob disease (178Asn CJD). The genotypic basis for the difference between FFI and 178AsnCJD lies in a polymorphism at codon 129 of the mutant prion protein gene: 129Met 178Asn results in FFI, 129Val 178Asn in CJD. The finding that the combination of a polymorphism and a single pathogenic mutation result in two distinct conditions represents a significant advance in our understanding of phenotypic variability. PMID- 7999321 TI - Working memory and bias in reasoning across the life span. AB - Age differences in syllogistic reasoning in relation to crystallized and fluid ability were studied in 278 adults from 19 to 96 years of age. Two reasoning tasks, the evaluation and the construction of conclusions for syllogisms of varying complexity and believability, a vocabulary test, and 3 tasks of working memory were administered. The magnitude of age-related variance on selected reasoning tasks was only partially reduced by statistically controlling measures of both working memory and vocabulary. Additional age-related effects on reasoning were found to be significantly associated with number of mental models and bias produced by conflict between belief and logic. A significant bias was also found toward acceptance of invalid syllogisms as valid, even when contents were abstract. These sources of error in logic are discussed in relation to Johnson-Laird's (1983) theory of mental models and Evan's (1989) account of bias in human reasoning. PMID- 7999322 TI - Caregiver depression after bereavement: chronic stress isn't over when it's over. AB - Although the adverse mental health consequences of caregiving for a relative with a progressive dementia are well documented, little is known about caregivers' adaptation after bereavement. This longitudinal study examined changes in three groups: continuing caregivers, who had been caregiving across a 4-year period (n = 98), bereaved caregivers, whose impaired relative died between Years 1 and 4 (n = 49), and controls (n = 107). Although a mean of 19.8 months had elapsed since bereavement by Year 4, bereaved and continuing caregivers did not differ on syndromal depression or depressive symptoms; both groups were significantly more depressed than controls. Time since bereavement was unrelated to depression or social support. Those caregivers who ruminated more about caregiving after bereavement reported more depression, greater stress, and greater social isolation. PMID- 7999323 TI - Age differences and interindividual variation in cognition in community-dwelling elderly. AB - The cognitive test performance of 897 community-dwelling elderly Ss, aged 70 years and over, was examined for age trends and interindividual variation. Data were subjected to factor analysis, and 3 factors emerged (Crystallized Intelligence, Fluid Intelligence, and Memory). Over the age span sampled, Crystallized Intelligence, Fluid Intelligence, and Memory all decreased with the decrease being greatest for Fluid Intelligence and least for Crystallized Intelligence. Interindividual variation increased for Fluid Intelligence and Memory, but not for Crystallized Intelligence. These findings give support to the view that crystallized intelligence is lower in the very old and that there is a greater degree of variability in test performance with advancing age. PMID- 7999324 TI - Predictors and outcomes of elder-care-based interrole conflict. AB - The authors propose and test a model of the predictors and outcomes of the role conflicts experienced by individuals simultaneously holding full-time employment and providing care for elderly parents. It is proposed that interrole conflict is predicted by physical and psychological involvement in elder care and predicts both partial absenteeism from work and psychological strain. In turn, psychological strain predicts marital interactions. Data from 141 full-time employees from 2 universities provided strong support for the proposed mediational model using LISREL VII. In contrast, 2 alternative models were not supported by the data. PMID- 7999325 TI - Dual-task assessment of age differences in automatic process development. AB - The present experiment assessed dual-task performance in 20 young (mean age 21) and 20 old (mean age 72) adults. Ss first received extensive single-task practice on consistent and varied search tasks. Next, they received dual-task practice in 2 conditions: (a) varied visual search plus varied memory search and (b) consistent visual search plus varied memory search. In the varied-varied condition, young and old adults showed similar dual-task decrements. These results, along with the current data in the literature, suggest that practice may play an important role in determining age-related dual-task differences (or lack thereof). In the consistent-varied condition, young adults attained single-task performance levels, because they had automatized the consistent task. Old adults were unable to match their single-task performance levels, indicating that they were unable to automatize the consistent task. PMID- 7999326 TI - Age and rate of activation in semantic memory. AB - Two word-primed picture-naming experiments were carried out to test the hypothesis that rate of activation in semantic memory is slower for older adults than for young adults. The presence of priming effects, both positive and negative, was taken as evidence of activation. In Experiment 1 there was no age difference in the time of onset of either facilitation or inhibition by primes. A computer simulation, based on a simple connectionist model, showed that slower processing would have only a minimal effect on the time of onset of priming effects under the assumptions of the model; however, offset of inhibition by primes would be delayed if processing rate were reduced. In Experiment 2 older adults showed inhibition by primes over a longer interval than did young adults, which was taken as evidence that the general slowing associated with aging extends to the transmission of activation at the earliest levels of cognitive processing. PMID- 7999327 TI - Variations in cognitive, perceptual, and psychomotor abilities across the working life span: examining the effects of race, sex, experience, education, and occupational type. AB - Cognitive, perceptual, and psychomotor abilities were examined across the working life span for different racial groups, taking into consideration sex, job experience, education, and occupational type. Data included scores on all subtests of the General Aptitude Test Battery for White, Black, and Hispanic employees. Age and sex generally accounted for a relatively small percentage of the variance in ability test scores when experience, education, and occupational type were controlled. Race accounted for a substantial amount of variance in test performance, even after controlling for education, experience, occupational type, and age. Findings are discussed in terms of the potential for specific experiences and continuing education to affect the maintenance of abilities at later points in the life span for all racial groups. PMID- 7999328 TI - Sex differences in the sensitivity of two self-report depression scales in older depressed inpatients. AB - Both the Geriatric Depression Scale (J. A. Yesavage et al., 1983) and the Beck Depression Inventory (A. T. Beck, A. J. Rush, B. F. Shaw, & G. Emery, 1979) were less effective in identifying depressed men than women in a sample of 191 geriatric psychiatric inpatients with major unipolar depression. From one quarter to one half of the men were missed cases, depending on the cutoff score used. Separate cutoff scores for older men and women on depression screening instruments may be appropriate. PMID- 7999329 TI - Age-cohort differences in treating symptoms of mental illness: a process approach. AB - This study examines age-cohort differences in conceptually organizing, observing, and responding to unclustered symptoms of mental illness. Older (M = 70.8) and younger (M = 19.9) adults sorted symptoms of depression, schizophrenia, and age associated changes into similarity groupings. Hierarchical cluster analysis showed that both older and younger adults sorted the statements similarly, although labels given for depressive symptoms differed across groups. Participants then reported which symptoms they had observed within their families and listed what actions were taken. Age groups showed significant differences in symptom reporting, with older individuals observing depressive symptoms less frequently. There were small differences in the kinds of actions reported. These results suggest that differences in help-seeking behavior for mental illness may be explained by differences in the way symptoms are observed by younger and older cohorts. PMID- 7999330 TI - Flashbulb memories in older adults. AB - In this study of age differences in flashbulb memory, groups of young and older adults gave detailed accounts of how they heard the news of the resignation of the British Prime Minister Margaret Thatcher. They were tested within 14 days after the event and again 11 months later. They also gave ratings for the encoding variables (surprise, emotion, importance, knowledge, and interest) and for frequency of rehearsal. Memories that met a strict criterion of consistency between the original and delayed responses were classified as flashbulb memories. Although 90% of young Ss had flashbulb memories, only 42% of the elderly met the criterion. The age groups also differed in the type of details remembered and in the relationship between the encoding and rehearsal variables and the occurrence of flashbulb memory. The age-related deficit in flashbulb memory is related to source amnesia and to a deficit in memory for context. PMID- 7999332 TI - Memory for spatial layouts in relation to age and schema typicality. AB - The hypothesis that prior experience, specifically a knowledge-based schema for typical house layouts, can compensate for age declines in spatial memory was evaluated in 4 experiments. Old and young adults explored and subsequently recalled house layouts presented 1 room at a time on a computer screen. The findings failed to support the compensation hypothesis in that schema-relevant layouts facilitated recall equivalently for the 2 age groups. Violation of a typical house schema had a more negative effect on recall of the older group. Individual differences in spatial visualization ability explained much of the age difference in performance but not the effects of schema manipulations. It was concluded that there is age invariance in the facilitatory effects of relevant prior knowledge on spatial memory but an age-related decrease in the ability to inhibit irrelevant prior knowledge. PMID- 7999331 TI - Caregiver ratings of personality change in Alzheimer's disease patients: a replication. AB - Caregivers of 26 patients with Alzheimer's disease (AD) rated current and premorbid personality patterns with the NEO Personality Inventory. Results replicated previous findings on the degree of change reported in a previous group of patients with mixed memory disorder diagnoses. After a diagnosis of AD, the patients were rated as significantly more neurotic, less extraverted, less open, and less conscientious. There were no rated differences of changes in the personality domain of Agreeableness. These results strengthen the usefulness of caregiver ratings of personality change of patients with memory problems who cannot be useful informants on their own behalf. PMID- 7999333 TI - Noninvasive determination of respiratory ozone absorption: the bolus-response method. AB - Morphometric studies in animals exposed to ozone (O3), and mathematical simulations of O3 transport in human lungs indicate that O3 toxicity is focal in nature, causing tissue damage that is more pronounced in the proximal alveolar region (the proximal end of the respiratory airspaces in our compartment models) than in other airways. These findings suggest that the internal distribution of O3 uptake must be known in order to assess health risk reliably. In previous work (Ultman and Ben-Jebria 1990), we developed a fast-responding chemiluminescent O3 analyzer and a small-scale O3 generator, both of which are suitable for respiratory measurements. The objective of the current research was to integrate these instruments into a bolus inhalation system capable of noninvasively measuring the longitudinal distribution of O3 absorption in intact human lungs. With this system we aimed to carry out baseline experiments in healthy men during quiet oral breathing at a respiratory flow rate of 250 mL/sec, determine the effect of alternative respiratory flow rates between 150 and 1,000 mL/sec, compare the absorption distribution during quiet oral breathing with that during quiet nasal breathing, and ascertain the influence of a peak inspired concentration between 0.3 and 4.0 parts per million (ppm). Ozone uptake (lambda) was expressed as the amount of O3 absorbed during a single breath relative to the amount in the inhaled bolus. Measurements of lambda were correlated with the penetration volume (VP) of the bolus into the respiratory tract. Values of VP less than 70 mL were considered to be associated with the upper airways, values between 70 and 180 mL were associated with the lower conducting airways, and values greater than 180 mL were associated with the respiratory airspaces. During quiet oral breathing, lambda increased smoothly with VP, with 50% of the inhaled O3 absorbed in the upper airways and the balance absorbed within the lower conducting airways. This compares favorably with the results of direct-sampling methods, which have indicated that 40.4% of continuously inhaled O3 is removed by the extrathoracic airways (Gerrity et al. 1988). The effect of increasing the respiratory flow, which occurs when people exercise, was to shift the lambda-VP distribution distally so that significantly less O3 was absorbed in the upper airways and more reached the respiratory airspaces. Compared with oral breathing, nasal breathing caused a proximal shift in the lambda-VP distribution to the extent that absorption in the upper airways increased from 50% to 80%.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 7999334 TI - A. J. C. Wilson. 80 years. PMID- 7999335 TI - Behavioral symptoms in dementia: theories and therapies. Cleveland, Ohio, September 30-October 1, 1993. International conference proceedings. PMID- 7999336 TI - Behavioral symptoms in dementia: theories and therapies. PMID- 7999337 TI - Managing challenging behaviors at home. PMID- 7999338 TI - Dementia care and respite services program. AB - In 1987 The Robert Wood Johnson Foundation announced the creation of the Dementia Care and Respite Services Program (DCRSP), the first national demonstration project to focus on day center and respite services for persons with dementia. The intent of $5.1 million, 4-year (1988-1992) program was to demonstrate that nonprofit day centers could provide financially viable programs and services needed by people with dementia and their caregivers. Seventeen grantees in 13 states, representing 21 different organizations and operating 24 day centers, participated in the project throughout the entire 4 years. The DCRSP has provided the first overview of dementia-specific day programs in the United States, with specific insight as to who is being served (e.g., participant and caregiver characteristics), types of assistance needed in relation to activities of daily living, and the most common behavior problems being exhibited. In addition, results of the 4-year project support the fact that community-based day centers can effectively care for people with dementia, a demand for these services does exist, and families consider these services of sufficient value that they are willing to pay for them out-of-pocket. Results also show that nonprofit day centers can become financially viable programs if attention is given to factors such as providing consumer-responsive services, charging what services actually cost, and having a high level of community visibility. The net result is increased net operating revenue with improved financial performance and enhanced long-term stability. PMID- 7999339 TI - Special care units for persons with dementia: expected and observed effects on behavioral symptoms. AB - Behavioral symptoms are common in nursing home residents with dementia, and have negative consequences for the residents, their families, staff members, and nondemented residents who live in close proximity to them. Special care units are intended to provide appropriate environments and methods of care that in turn are expected to reduce the incidence of behavioral symptoms. Studies of the effectiveness of special care units in reducing behavioral symptoms have had contradictory findings. Further research is needed to identify the particular environments and methods of care that are effective in reducing specific behavioral symptoms in these residents. PMID- 7999340 TI - Quality of life in Alzheimer disease. AB - Quality of life (QOL) in dementing illness comprises the same areas as in people in general. Domains of QOL in patients with Alzheimer disease (AD) include competent cognitive functioning, the ability to perform activities of daily living and to engage in meaningful time use and social behavior, and a favorable balance between positive emotion and absence of negative emotion. Dementing illness can strip the person of normal indicators of personhood. Formal assessment of such QOL indicators can counteract the tendency to view QOL as irrelevant to dementing illness. A preliminary report of ongoing research to evaluate a special care unit for patients with AD includes findings on measuring positive behaviors and both positive and negative emotion. Emotions judged from direct observation showed promising reliability and validity. Thus, it may be possible to assess the preferences, aversions, and response to interventions of dementia patients even when the patients cannot report their evaluations. PMID- 7999341 TI - The patient's perspective: the Alzheimer's association. PMID- 7999342 TI - Ethics of behavior control: a panel discussion. PMID- 7999344 TI - Assessment of behavioral symptoms in Alzheimer disease. PMID- 7999343 TI - Culture-fair behavioral symptom differential assessment and intervention in dementing illness. AB - Ethnically diverse populations are not represented in the dementia-related noncognitive behavioral symptom research arena. Some of the obstacles are structural, centering around the lack of inclusion of ethnic minority groups within existing projects. These impediments are surmountable by the systematic targeting and incorporation of ethically diverse populations in research and the deployment of a variety of research-related outreach approaches. The more formidable barriers are conceptual. They relate to the need to differentiate cultural factors from socioeconomic and social status (SES) artifacts and to include life-long exposure to various forms of prejudice and discrimination, all of which can come together in the late-life manifestation of behavioral symptoms. A culture-fair behavioral assessment and intervention model is presented. It allows researcher and clinician alike access to ethnocultural data, while differentiating SES influences. A comparative Hispanic/Anglo dementia caregiver pilot study has provided a partial test of the model with statistically significant outcomes. Two-tailed t tests (p < or = 0.05) uncovered ethnic group differences with respect to four specific dimensions of caregiving. The differences were demonstrated around reactivity to caregiving burden, caregiver health status, coping and helpseeking styles, and configuration of social support received from social network members. Further multiple regression analysis sustained the observed differences despite income, education, and mean age variance between the two ethnic groups. The model has an overall multicultural applied intent. More study is indicated. PMID- 7999345 TI - Relationship of behavioral complications and severity of dementia in Japanese elderly persons with dementia. AB - Management of behavioral symptoms in patients with age-associated dementia is essential to improve quality of life for them and their caregivers. Although many results have been reported about the burden on caregivers of demented relatives, no guidelines for managing behavioral symptoms of demented patients have been developed. One of the major reasons for the lack of practical guidelines is that dementia behavioral syndromes have been understood to be a socio-psycho-somato disorder. Also, no standardized procedures to assess behavioral symptoms are yet available. In this article, the relationship of behavioral symptoms to the severity of dementia is examined by different assessment procedures, with the aim of understanding their manifestation mechanisms. In 223 patients with age associated dementia, including 99 with Alzheimer type dementia, 32 behavioral symptoms were assessed according to frequency, severity, and intensity, which was assessed corresponding to a value score multiplied by a frequency score multiplied by a severity score. The results by an analysis of covariance with intensity, frequency, and severity of symptoms as dependent variables; severity of dementia as an independent variable; and age, sex, and activities of daily living scores as covariates, indicated that some behavioral symptoms are significantly related to severity of dementia, which is hypothesized to correspond to organic changes in the brain, while other symptoms are not related to severity of dementia. Also, the pattern of relationship varied according to assessment procedures.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7999346 TI - Neurobiologic bases of noncognitive behavioral problems in Alzheimer disease. AB - Abnormalities of neurochemical systems in Alzheimer disease, which are potentially relevant to the pathophysiology of such noncognitive problems as agitation and depression, have been demonstrated. However, the role of these abnormalities in the etiology of noncognitive problem behaviors remains poorly understood. Such abnormalities in brain noradrenergic and serotonergic systems are of particular interest because of their apparent involvement in normal regulation of mood, arousal, and aggressive behavior. The nature of the noradrenergic abnormalities in Alzheimer disease is particularly complex, with evidence suggesting both structural damage and compensatory increased norepinephrine release from remaining noradrenergic neurons. Currently available drugs that alter brain noradrenergic or serotonergic activity should be evaluated for efficacy in the management of noncognitive behavioral disorders complicating Alzheimer disease. PMID- 7999347 TI - The phenomenology of behavior: an overview of behavioral principles. AB - Noncognitive behavioral symptoms are common in dementia and present challenges to caregivers, clinicians, and researchers. This article reviews these noncognitive symptoms from a behavioral point of view and suggests that both operant and associative conditioning principles might apply. A central feature underlying these approaches is a detailed, specific description of the behavior. Careful description combines the approach of the phenomenologist and the behaviorist but remains underappreciated and underdeveloped. PMID- 7999348 TI - Behavioral treatment of depression in patients with dementia. AB - This article provides an overview of the theory, clinical application, and research data on behavioral treatment of depression in dementia patients. Behavioral theory of depression in nondemented adults indicates that decreased positive person-environment interactions initiate and maintain a cycle of depression that may be amenable to treatment. This same cycle is discussed as it appears in demented adults, and treatment is suggested. This treatment focuses on altering the aversive events and interactions that maintain patient depression, by increasing pleasant events and interactions, maximizing cognitive abilities, and teaching caregivers strategies for behavior change and effective problem solving. A 9-week clinical research protocol is provided with specific session-by session content. Preliminary data are presented from a controlled clinical trial of this approach. Results thus far indicate that behavioral treatment is effective in reducing depression in patients with Alzheimer disease and in reducing the level of depression in their caregivers. The implications of these findings on future clinical care of patients and research directions are discussed. PMID- 7999349 TI - Psychotherapy for individuals with Alzheimer disease. AB - Individuals with Alzheimer disease often experience depression, anger, and other psychological symptoms. Various forms of psychotherapy have been attempted with these individuals, including insight oriented therapy and less verbal therapies such as music therapy and art therapy. Although there are few data-based outcome studies that support the effectiveness of these interventions, case studies and descriptive information suggest that they can be helpful in alleviating negative emotions and minimizing problematic behaviors. PMID- 7999350 TI - The use of behavior modification with Alzheimer patients: values and limitations. AB - Behavior modification principles are described as they relate to patients with Alzheimer disease and related disorders. Sample cases are used to illustrate application of the principles to both an inpatient setting and a home setting. Values and limitations along with recommendations are suggested. PMID- 7999351 TI - The uniqueness of the nursing perspective in managing behavioral problems. PMID- 7999352 TI - Functional communication with AD patients: a caregiver training program. AB - The loss of functional communication in Alzheimer disease (AD) results from the disproportionate breakdowns in the pragmatic and semantic areas of language in these patients. Communication breakdown is regularly listed among the top four stressors in measures of stress and burden of AD caregivers. A caregiver training program designed around seven specific communication strategies can be used to alter communication interactions. As a pilot program, the acronym FOCUSED organized the seven strategies for easy recall (Face-to-face, Orientation, Continuity, Unsticking, Structure, Exchanges, and Direct). Significant differences in both attitude toward AD patients, knowledge of AD, and knowledge of communication strategies were shown in comparisons of pre- and posttraining assessments. PMID- 7999353 TI - Mullerian-inhibiting substance secretion is delayed in XX sex-reversed dog embryos. AB - Sertoli cell secretion of Mullerian-inhibiting substance (MIS) begins shortly after testis differentiation. Mullerian ducts regress following MIS exposure during an embryonic critical period. In dogs with XX sex reversal, Mullerian ducts persist in the presence of testicular tissue. This study was conducted to determine whether MIS is present in ovotestes of XX sex-reversed embryos during the period for Mullerian duct regression in normal males. XX sex-reversed embryos and normal littermates were identified by a combination of karyotype and gonadal histology. The degree of regression in the adjacent Mullerian duct was scored. Immunohistochemical staining was used to detect MIS in the contralateral gonad. Testicular differentiation and MIS secretion were identified in XY embryos at all ages studied (35-46 days). Seminiferous tubules were not observed in gonads of embryos at risk of XX sex reversal between 35-38 days (n = 15), but were observed at 40 and 46 days (n = 3). Although positive staining for MIS was observed in ovotestes, adjacent Mullerian ducts persisted. The degree of seminiferous tubule development was reduced and MIS secretion was delayed in ovotestes, compared to normal testes. Mullerian duct persistence in this model is apparently due to an abnormality in the quantity and timing of MIS secretion during embryonic development. PMID- 7999354 TI - Studies on FGF-2: nuclear localization and function of high molecular weight forms and receptor binding in the absence of heparin. AB - Multiple forms of FGF-2 have been shown to exist in many cell types. These different species of molecular masses of 18, 21.5, 22, and 24 kDa are all translated via the use of alternate initiation codons. The three forms of HMW FGF 2 initiate at CUGs codons, whereas the 18 kDa form initiates at an AUG codon. The entire 18 kDa sequence is contained within the larger forms of HMW FGF-2 as the AUG codon is 3' to the CUG codons. Although the 18 kDa form FGF-2 is localized primarily in the cytosol, a significant fraction of the HMW FGF-2 has a nuclear location. The nuclear localization of HMW FGF-2 is determined by amino acid residues in the amino-terminal extended sequence. The residues required for nuclear localization appear to be RG repeats that are found at multiple sites within the amino-terminal extension of HMW FGF-2. The nuclear localization of HMW FGF-2 suggested that these species may have unique properties. By selecting permanent transfectants of 3T3 cells expressing HMW, 18 kDa FGF-2, or all forms of FGF-2, we have found that HMW FGF-2 can endow cells with a phenotype different from that of cells expressing 18 kDa FGF-2. These cells are transformed by what appears to be the intracellular action of HMW FGF-2. The interaction of FGF-2 with heparin has also been examined.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7999356 TI - Role of fibroblast growth factors as inducing agents in early embryonic development. AB - To assess the potential role of a molecule in development we need to know three things: 1) what are the biological activities of the molecule, 2) what is its expression pattern, and 3) what are the consequences of removing it from the embryo? In the case of the FGF family in Xenopus embryos we have quite a lot of information about all three questions. Most members of the family can induce mesoderm from isolated animal caps, thus mimicking the natural "ventral vegetal" inducing signal operative in the blastula. This activity can be exerted on isolated, disaggregated cells and does not involve a change in division rate. When overexpressed from injected mRNA, the activity of FGFs depends largely on whether or not they possess a signal sequence, showing the importance of secretion in the inductive process. In addition to the mesoderm-inducing activity, there are effects of overexpression on whole embryos which lead to a suppression of anterior structures. Three types of FGF have so far been cloned from Xenopus: direct homologs of each of the mammalian types FGF-2 and FGF-3, and eFGF ("embryonic FGF"), which is equidistant in sequence from mammalian FGF-4 and FGF-6. Attempts to find homologs of mammalian FGF-5 and FGF-7 in Xenopus have proved unsuccessful. All three types of Xenopus FGF are expressed in early development. FGF-2 and eFGF are present in the oocyte and fertilized egg, and are thus both available at the time of mesoderm induction.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7999355 TI - Transcriptional regulation of the murine k-fgf gene. AB - Embryonal carcinoma (EC) cells provide a useful model system for studying the roles of growth factors during early mammalian development. In 1988, we determined that EC cells express a member of the fibroblast growth factor (FGF) family that cannot be detected after EC cells undergo differentiation. Attempts to understand how differentiation regulates the production of FGFs led to the finding that EC cells express the fibroblast growth factor k-FGF (FGF-4), whereas there is a large decrease in the steady state levels of k-FGF mRNA when EC cells differentiate. This suggested that transcription of the k-fgf gene is repressed when EC cells differentiate. To investigate this possibility, we prepared a series of reporter gene constructs containing various regions of the murine k-fgf gene. These constructs were transfected into two mouse EC cell lines and one mouse embryonic stem (ES) cell line. We determined that the mouse 5' flanking region cannot support expression of the reporter gene. In both EC and ES cell lines, expression of the reporter gene is elevated greatly by the addition of a 316 bp region from the third exon of the murine k-fgf gene. Sequence analysis of the 316 bp region identified one and possibly two conserved octamer binding motifs. These sequences are likely to be involved in regulation of the k-fgf gene, because differentiation of EC cells is known to reduce the expression of octamer binding proteins, including Oct-3. To test the possible role of octamer binding proteins, we examined the expression of our reporter gene constructs in F9-differentiated cells and in PYS-2 cells.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7999357 TI - Cumulus cells secrete a meiosis-inducing substance by stimulation with forskolin and dibutyric cyclic adenosine monophosphate. AB - The role of the cumulus cells in initiating the resumption of meiosis after exposure to forskolin and dbcAMP was studied in the mouse. The resumption of meiosis was monitored by the percentage of germinal vesicle breakdown (GVBD) and polar body formation (PB). The cumulus-enclosed oocytes (CEO) and denuded oocytes (DO) were cultured with and without hypoxanthine (HX) in the culture medium. Three types of experiments were performed: (1) Effect of forskolin on spontaneous resumption of meiosis, i.e. cultures without HX, and two experiments in which HX is present throughout the culture: (2) Effect of transient exposure to forskolin or dibutyric-cyclic adenosinemonophosphate (dbcAMP) on GVBD prior to continued culture without forskolin or dbcAMP (oocyte priming). (3) Priming of CEO with forskolin for 2 hr, separation of cumulus cells and oocytes, followed by coculture of rejoined cumulus cells and oocytes, or coculture of the cumulus cells and new, unprimed DO. (1) Forskolin inhibited a spontaneous resumption of meiosis in a dose-dependent manner during the first 5 hr of culturing. After 22 hr all controls and CEO resumed meiosis, whereas only half of the DO did. (2) At least 1 hr of priming the CEO with forskolin is needed to induce GVBD and PB formation, but forskolin inhibited the resumption of meiosis when present for 24 hr. Similar results were obtained with a high concentration of dbcAMP. (3) A separation and rejoining of oocytes and cumulus cells after priming induced the resumption of meiosis in a significantly greater number of oocytes than in the control oocytes which were not primed.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7999358 TI - Correlation of zona-binding with oocyte maturation and sperm motility in rhesus monkeys by hemizona assay. AB - The hemizona assay (HZA) in Rhesus monkeys was employed to study the correlation of zona-binding ability with sperm motility or with naturally developing oocytes at various maturational stages. Oocytes from unstimulated ovaries were retrieved within 2 hr from monkeys sacrificed for vaccine production (in reproductive season, but with their menstrual cycles not determined). Oocytes were divided into four groups based on their morphological maturation: 1) Oocytes surrounded by more than one cumulus layer (MC); 2) Oocytes retaining intact germinal vesicle nuclei (GV); 3) Oocytes with germinal vesicle breakdown showing distinct perivitelline space (PVS); and 4) Oocytes extruding the first polar body (PB1). The mean numbers of sperm bound to hemizona for PB1, PVS, GV, and MC groups were 132.9 +/- 12.0, 71.5 +/- 10.1, 36.1 +/- 4.0, and 20.1 +/- 2.9 (Mean +/- SE), respectively. The four groups showed significant differences from each other in sperm/egg binding ability (P < 0.01). The number of bound sperm significantly increased with oocyte maturation. The present study also showed that zona-binding ability was also affected by sperm motility. For sperm with 67.7% motility and sperm with 31.2% motility, the average numbers of bound sperm were 43.5 +/- 2.2 and 25.3 +/- 2.9 (Mean +/- SE), respectively. There was significantly higher binding ability for sperm with higher motility (P < 0.01). The results suggest that: 1) The rhesus monkey model can serve as a very sensitive model for studying sperm/egg interaction by HZA; 2) Sperm motility positively correlated with sperm/egg binding; and 3) Sperm/egg binding ability increases with oocyte maturation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7999359 TI - Epidermal growth factor enhances oocyte maturation in pigs. AB - Epidermal Growth Factor (EGF) has been reported to stimulate nuclear maturation in porcine oocytes (Sommer et al., 1992). The objective of this experiment was to test the effect of EGF alone or in combination with gonadotropins and follicular shell coculture, on cytoplasmic maturation of oocytes in vitro. A preliminary experiment tested the effective dose of EGF for stimulation of oocyte nuclear maturation in our culture system. Nuclear maturation rates (MII%) of 67.2 +/- 4.6, 81.1 +/- 8.6, and 80.7 +/- 5.1 for oocyte complexes cultured in the presence of 0.1, 1, and 10 ng/ml EGF, respectively, were significantly higher (P < 0.05) than for oocytes cultured in the absence of EGF (18.1 +/- 9.4%). In the main experiment a 2 x 2 x 2 factorial random complete block design was used to examine the effect of EGF (1.0 ng/ml) alone or in combination with gonadotropins and follicular shell coculture on cytoplasmic maturation. Cytoplasmic maturation was evaluated by the ability of oocytes to decondense sperm nuclei after sperm penetration. EGF alone did not stimulate cytoplasmic maturation in oocytes in vitro (P > 0.05). However, EGF showed a positive interaction (P < 0.05) with gonadotropin treatment on male pronuclear formation. We conclude that EGF alone can stimulate nuclear maturation in pig oocytes, and EGF can interact with gonadotropins to enhance cytoplasmic maturation. A high level of cytoplasmic maturation of in vitro matured pig oocytes could be achieved using a combination of EGF, gonadotropin, and follicular shell supplementation to the culture environment. PMID- 7999361 TI - Introduction: fibroblast growth factors and their receptors in development and disease. PMID- 7999360 TI - Fibroblast growth factors and their receptors in development and disease. Ames, Iowa, September 17-20, 1993. Proceedings. PMID- 7999362 TI - Targeted disruption of int-2 (fgf-3) causes developmental defects in the tail and inner ear. AB - The int-2 gene (also designated fgf-3) was originally identified because its transcription is activated by the nearby integration of mouse mammary tumor virus in virus-induced tumors. Molecular analyses have revealed that the int-2 gene produces at least four mRNAs, all of which encode a protein that has 40-50% amino acid sequence similarity with the fibroblast growth factors (FGFs). Int-2 gene expression is localized to a small number of discrete sites in the developing mouse, but has not been detected in any nonneoplastic adult tissue. The expression data and the amino acid sequence similarity with the FGFs suggested several potential roles for int-2 during normal development. To evaluate these possibilities, we initiated a genetic analysis of int-2. A gene-targeting protocol was used to generate embryonic stem (ES) cells that are heterozygous for an insertion of the neo(r) gene into the first protein-coding exon of int-2. These cells were used to establish a line of mice that carry the gene disruption. Animals that are heterozygous for the int-2neo allele are normal and fertile. Homozygous mutants survive embryonic development and can be visually identified after 12.5 days of gestation by a short, initially dorsally curled tail. This defect is potentially due to the disruption of int-2 expression in the primitive streak/tail bud. Most of the homozygous mutants die at or soon after birth, but several have survived to adulthood. In addition to the tail phenotype, the surviving homozygotes show, to varying extents, symptoms characteristic of inner ear abnormalities.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7999363 TI - Heparan sulfate fibroblast growth factor receptor complex: structure-function relationships. AB - Splice variations in genes coding for the transmembrane FGF receptor (FGFR) result in isoforms that vary in the ectodomain, intracellular juxtamembrane domain, and the intracellular kinase domain. An analysis of biochemical functions of distinct recombinant isoforms expressed in baculoviral-infected insect cells allowed generation of models for function of splice variants in both the ecto- and intracellular domains. A structural model for the ectodomain of the FGFR is proposed as follows. Alternately-spliced immunoglobulin-like disulfide Loop I, which is not required for ligand-binding, is sufficiently interactive with the base FGF binding site formed by Loops II and III to modify ligand affinity and affect interaction of the receptor with heparan sulfate cofactor. The NH2 terminal domain of Loop II, which is highly conserved across all isoforms, exhibits a 19-residue heparin-binding domain which is obligatory for FGF binding. Heparin protects a 30-kDa ligand-binding fragment from proteolysis that is composed of Loop II, the inter-Loop II/III sequence, and the NH2-terminus of Loop III. This suggests that the high-affinity FGF receptor complex is an intimate ternary complex of transmembrane tyrosine kinase, heparan sulfate glycosaminoglycan, and FGF, each of which have interactive binding domains for the other and may contribute to specificity of the FGFR complex. Although Ig Loop II, the inter-Loop II/III sequence, and the NH2-terminus of Loop III with heparan sulfate form the base FGF binding site, mutually exclusive alternate splicing of two exons coding for the COOH-terminal half of Loop III determines which specific members of the FGF ligand family bind with high affinity to the base site. A kinase- and tyrosine phosphorylation site-defective splice variant, FGFR type 2, acts as a dominant-negative suppressor of phosphorylation of specifically tyr-653 in the catalytic domain of the kinase, with less effect on phosphorylation of tyr 766 in the COOH-terminal tail. We propose that phosphorylation of tyr-766, which is required for interaction of phospholipase C gamma 1 (PLC gamma 1) with the receptor, may occur by a cis-intramolecular mechanism within FGFR monomers, while phosphorylation of tyr-653, which is required for phosphorylation of PLC gamma 1, may occur by a trans-intermolecular mechanism between monomers within kinase homodimers. From the combined results, we propose a model whereby increasing concentrations of FGF may control FGF-mediated signal transduction by heterodimerization of different FGFR monomers. Different monomers arise by regulated combinatorial alternate splicing that alters both the extracellular and intracellular domains. PMID- 7999364 TI - Oocyte structure and follicular steroid concentrations in superovulated versus unstimulated heifers. AB - A highly variable yield of viable embryos in superovulated cattle is a major hindrance to the embryo transfer industry. To trace the cause of this problem, investigations were carried out on the intrafollicular steroids and structure of oocytes originating from follicles of follicular stimulating hormone (FSH) stimulated (superovulated) and unstimulated heifers. Unstimulated heifers were slaughtered at midcycle, or administered cloprostenol (PG) at midcycle and slaughtered after 24, 48, or 72 hr, while superovulated heifers were administered 4 injections of pFSH (2 injections per day) and slaughtered 12 hr later, or administered 6, 7, or 8 injections of FSH in combination with PG at the 5th and 6th injection, and slaughtered 24, 36, or 60 hr, respectively, after the first PG injection. The follicular fluid from the largest (presumptive dominant) follicle of the unstimulated heifers and from potentially ovulatory follicles (> or = 8 mm in diameter) of the superovulated heifers were assayed for estradiol-17 beta (E2) and progesterone (P4), while the oocyte cumulus complexes from such follicles were processed for transmission electron microscopy. The mean E2 and especially P4 concentrations of the potentially ovulatory follicles of the superovulated heifers were lower than similar follicles of the unstimulated animals (83.7 +/- 76.7 ng/ml vs. 208.1 +/- 357.0 ng/ml, P > 0.05 and 31.1 +/- 38.7 ng/ml vs. 150.3 +/- 202, P < 0.05, respectively). The unstimulated oocytes had, in general, spherical oocyte nuclei and compact nucleoli before PG administration, while after PG, undulation of the nuclear envelope and nucleolus vacuolization was characteristic.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7999365 TI - Function of FGF-4 in limb development. AB - The apical ectodermal ridge plays a central role in limb development through its interactions with the underlying mesenchyme. Removal of the AER results in cessation of limb outgrowth and leads to truncation of the limb along the proximo distal axis. The many functions attributed to the ridge include maintenance of the progress zone mesenchyme. Here, cells are stimulated to proliferate, are maintained in an undifferentiated state, and are assigned progressively more distal positional values as the limb grows. The AER also functions to maintain the activity of the polarizing region, a region of mesenchyme which is thought to provide the primary signal for patterning along the antero-posterior axis. We have begun to explore the function of fibroblast growth factor-4 (FGF-4) during limb development. FGF-4, which encodes an efficiently secreted protein, is expressed in the AER. We have previously demonstrated that FGF-4 protein can stimulate limb mesenchyme proliferation and can induce the expression of a downstream homeobox gene, Evx-1 (homologue of the Drosophila even-skipped gene), that is normally regulated by a signal from the AER. To determine to what extent FGF-4 protein can substitute for the AER to allow normal limb outgrowth, we performed experiments on the developing chick limb in ovo. Remarkably, we find that after AER removal, the FGF-4 protein can provide all the signals required for virtually normal outgrowth and patterning of the limb.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7999366 TI - Role of FGFs in skeletal muscle and limb development. AB - Fibroblast growth factors (FGFs) are a family of nine proteins that bind to three distinct types of cell surface molecules: (i) FGF receptor tyrosine kinases (FGFR 1 through FGFR-4); (ii) a cysteine-rich FGF receptor (CFR); and (iii) heparan sulfate proteoglycans (HSPGs). Signaling by FGFs requires participation of at least two of these receptors: the FGFRs and HSPGs form a signaling complex. The length and sulfation pattern of the heparan sulfate chain determines both the activity of the signaling complex and, in part, the ligand specificity for FGFR 1. Thus, the heparan sulfate proteoglycans are likely to play an essential role in signaling. We have recently identified a role for FGF in limb bud development in vivo. In the chick limb bud, ectopic expression of the 18 kDa form of FGF-2 or FGF-2 fused to an artificial signal peptide at its amino terminus causes skeletal duplications. These data, and the observations that FGF-2 is localized to the subjacent mesoderm and the apical ectodermal ridge in the early developing limb, suggest that FGF-2 plays an important role in limb outgrowth. We propose that FGF 2 is an apical ectodermal ridge-derived factor that participates in limb outgrowth and patterning. PMID- 7999367 TI - Eutherian phylogeny as inferred from mitochondrial DNA sequence data. AB - The phylogenetic relationships among Primates, Artiodactyla, Cetacea, Carnivora, and Rodentia were estimated from the amino acid sequences of proteins encoded by the mitochondrial genomes, for which entire nucleotide sequence data are available, using Marsupialia, Aves, and Amphibia as outgroups. The overall evidence of the maximum likelihood, as well as maximum parsimony, analyses strongly suggests that Rodentia is an outgroup to the other four eutherian orders, and that Cetacea and Artiodactyla form a clade with Carnivora as a sister taxon, consistently with the molecular phylogenetic studies of previous authors. However, analyses of individual proteins do not necessarily conform to this conclusion, and some of the proteins reject the putatively correct tree with nearly 5% significance. Furthermore, the 12S mitochondrial ribosomal RNA sequences do not give the putatively correct tree irrespective of the alignments and of the phylogenetic methods, although the tree is not rejected with a statistical significance. The 16S ribosomal RNA sequences give the putatively correct tree with our sequence alignment when the ML method is used, but the result depends on the alignment and on the choice of outgroup species. These results illustrate the limitation of the ribosomal RNA data alone in phylogenetic inference, and suggest that we must analyze as many genes as possible and synthesize the results to draw a reliable conclusion. PMID- 7999368 TI - A possible link between molecular evolution and tissue evolution demonstrated by tissue specific genes. AB - In this paper, we reviewed our recent works on a possible link between molecular evolution and tissue evolution. The evolutionary rates of genes that are expressed tissue specifically were shown to differ widely to one another, depending on tissues: Brain specific genes evolve with significantly slower rate than immune specific genes. The tissue dependence of molecular evolutionary rate strongly suggests the presence of functional constraints against molecular changes from tissue level. A molecular phylogenetic analysis of tissue specific isoforms that are identical to one another in function, but differ only in tissue distribution revealed frequent gene duplications and rapid accumulations of amino acid substitutions during the early evolution of chordates, where rapid evolution at the tissue or organ levels is thought to have occurred. On the basis of functional constraints, a possible explanation for the correlation between evolution at the two levels was presented. PMID- 7999369 TI - Evolution of pathogenic viruses with special reference to the rates of synonymous and nonsynonymous substitutions. AB - For pathogenic viruses such as human immunodeficiency virus (HIV), hepatitis B virus (HBV), hepatitis C virus (HCV), human influenza A virus, and human T-cell leukemia virus type I (HTLV-I), the evolutionary features were briefly reviewed with special reference to the rates of synonymous and nonsynonymous substitutions. In particular, these rates were discussed in connection with the neutral theory of molecular evolution. It was common to all the five pathogenic viruses that the rate of synonymous substitution was higher than that of nonsynonymous substitution particularly when the entire gene regions were compared between different isolates. This suggests that the viral proteins are quite conservative to functional and structural changes even though most of these viral genomes are evolving at a speed extraordinarily higher than their host genomes. Thus, this feature is consistent with the neutral theory. However, it is also pointed out that positive selection may be operating on some specific sites such as antigenic sites in order for the pathogenic viruses to escape from the host immune system. PMID- 7999370 TI - Evolution of glutamine synthetase genes is in accordance with the neutral theory of molecular evolution. AB - Evolution of glutamine synthetase gene is discussed on the results of DNA sequence analysis of the gene. Thirty DNA sequences of various organisms spanning from prokaryotes to eukaryotes were collected from the DNA data banks and translated first, they were aligned next, then evolutionary distances were computed, and molecular phylogeny was finally estimated. The results of the alignment reveal that functionally important regions of glutamine synthetase have been evolutionarily more conserved than the remaining regions. The evolutionary distances computed also show that the rate of synonymous substitution is higher than that of nonsynonymous substitution. These are well in accordance with the neutral theory of molecular evolution. Besides, the molecular phylogeny obtained shows that the origin of glutamine synthetase gene is much earlier than the divergence between eukaryotes and prokaryotes, suggesting that the gene is one of the oldest genes functioning now. PMID- 7999372 TI - Mammalian phylogeny inferred from multiple protein data. AB - On the basis of multiple protein data, the phylogenetic relationships among the major clades of eutherian mammals, Primates, Cetacea, Artiodactyla, Carnivora, Lagomorpha, Myomorpha, and Caviomorpha, were analyzed by the maximum likelihood (ML) method, together with the maximum parsimony (MP) method and the neighbor joining (NJ) method. Using nineteen protein data, we first reexamined the hypothesis of rodent polyphyly proposed by Graur et al. (1991) based on the four taxon system, consisting of human, mouse (or rat), guinea-pig and an outgroup. The ML analysis does not support the rodent polyphyly, but strongly favors the traditional view of rodent monophyly representing the Myomorpha-Caviomorpha association. In the second analysis, the phylogenetic position of Lagomorpha were reexamined using three sets of multiple protein data, 13 mitochondrial DNA-coded proteins from rodents, rabbit, human, seals, bovine, whales and opossum, 25 protein data from human, rabbit and rodents and an outgroup, and 20 protein data from human, rabbit, bovine (or pig) and rodents. Our analysis favors the closer affinity of Lagomorpha to Primates than to Rodentia. The branching sequence of seven mammalian groups revealed by the present analyses is as follows: Myomorpha Caviomorpha clade (Rodentia), rabbit, Primates, Carnivora, and Artiodactyla Cetacea clade. Judging from the branch lengths measured by the numbers of synonymous substitutions, a series of divergence of these mammals is likely to be bush-like. The rapid rate of rodent evolution was reexamined in the light of the new phylogeny. PMID- 7999371 TI - A note on neutralism. PMID- 7999373 TI - A polymorphic microsatellite marker from the tropical tree Dryobalanops lanceolata (Dipterocarpaceae). AB - Di-nucleotide microsatellites were isolated from a genomic library of a tropical tree species, Dryobalanops lanceolata, in Sarawak, for the purpose of using them as hypervariable genetic markers to study the pollen-mediated gene flow. Among 1600 recombinant clones, in total 20 clones gave positive signals when hybridized with oligonucleotides with the three different repeat motifs, GT, CA and CT. Estimations of abundance of (GT)n/(CA)n and (GA)n/(CT)n dinucleotide repeats in D. lanceolata genome revealed to be one in every 84 kb and 80 kb, respectively. Among six sequenced microsatellite loci, one was selected to synthesize PCR primers to amplify the microsatellite. PCR product size of the locus was variable among different individuals, which is attributed to the different number of di nucleotide repeats. The same microsatellite genotype was detected in the trunk and canopy of a single large tree, indicating the utility of trunk tissue as the source of DNA for the population genetic study of tropical tree species, the canopy of which is usually difficult to approach. PMID- 7999374 TI - Is health care a commodity: how will purchasing improve the National Health Service? AB - Through the reforms to the National Health Service in 1990 an internal market for public health care provision in the United Kingdom was introduced. As part of this new system of care, responsibility for purchasing of health care was separated from that for its provision. The new purchasing function, undertaken by district health authorities and fundholding general practices, has created the opportunity for improvements in health and higher standards of care to be achieved through new and explicit mechanisms. However, the purchasing function has not yet realized its full potential to achieve beneficial change, partly because traditional behaviours have not yet adapted to the new system of care and partly because specific aspects of the internal market are creating barriers and perverse incentives. This paper discusses these issues and identifies the important barriers which have still to be overcome if purchasing is to be the driving force for change in the new National Health Service. PMID- 7999375 TI - Health and health care in the English-speaking Caribbean: a British public health physician's view of the Caribbean. AB - People of Caribbean origin form one of the United Kingdom's most important ethnic minority groups but health conditions in the West Indies are not well understood in the UK. This review outlines past and present health conditions in the West Indies and describes the system of health care and some of the problems it faces at present. The last 30 years have seen a transition from a pattern of high childhood mortality to high mortality from chronic non-communicable diseases in adult life. Over the last ten years the severity of economic conditions undermined this progress, with the threatened re-emergence of malnutrition and infectious diseases as important health problems. Although most people in the region have access to health care, the quality and outcomes of care may be compromised by financial constraints and an unresponsive management system. Adopting modern approaches to planning and managing the health system might be one path to improvement, one to which public health professionals could make a significant contribution. PMID- 7999376 TI - Whither lay epidemiology in UK public health policy and practice? Some reflections on occupational and environmental health opportunities. AB - The problems of public and media interpretations of epidemiological studies--for instance, confusion about contradictory findings which indicate the hazards or advantages of consuming certain foods or drink or taking particular medical or pharmaceutical products, and one study on radiation exposure apparently overturning the results of another study within weeks or months--indicate the need for better communications by scientists, better education for the public on hazards and risks, and a better flow of information to the public on such topics. One democratic means for achieving this end, which would also increase community and worker participation in and control of health research affecting them, is through lay or community epidemiology. This subject has been discussed for some years but very little action has resulted in England. The concept relates to community groups and employees carrying out epidemiological research and using the expertise of professional epidemiologists. The epidemiologists work for and with the community rather than on the community: an experience which professionals may find threatening. Nevertheless, the World Health Organization and other groups rightly support such an empowering initiative, and some ways of introducing the approach into England are discussed. PMID- 7999377 TI - A postal survey evaluation of prostatectomy. AB - BACKGROUND: The aims of this study were to determine the prevalence of urinary symptoms after prostatectomy, and the relationship between pre- and post operative symptoms. METHODS: A retrospective postal survey was carried out, on an unselected series of patients in Leicestershire, one to two years after transurethral resection. Four hundred and sixty-five men received a questionnaire, and of these 78 per cent responded. RESULTS: The operation relieved 92 per cent of all preoperative urge-incontinence, but 3 per cent of those who were continent beforehand developed urge-incontinence. Urgency and hesitancy also responded well. Nocturia, frequency and dribbling were the least responsive. There was a general tendency for symptoms to persist rather than develop post-operatively. CONCLUSIONS: Prostatectomy is an effective intervention, particularly for cases with urge-incontinence, urgency, incontinence or hesitancy. These results are consistent with those of other, prospective, studies. Postal surveys may provide a cheap and effective method of evaluating local prostatectomy services. PMID- 7999378 TI - A framework for commissioning services for people with learning disabilities. AB - The needs of people who have global developmental learning disabilities (mental handicap) are complex and lifelong. Unless social and health service commissioners agree a framework for conceptualizing their need, there is a danger that services could become fragmented. This paper uses the World Health Organization's model of disabilities to put in context these needs. Using this model it is logical for health services to focus on (1) ensuring access to the full range of primary and secondary health services, (2) reducing the occurrence and severity of intellectual and associated impairments and (3) ensuring the provision of assessment and treatment of behaviour disorders and associated mental health problems. Some of these inputs are required before birth and in early childhood, but a number of people will require health services throughout life because of the presence of other disabilities or continuing behaviour and/or mental health problems. At school age, the education authority should provide the lead in ensuring the best physical and social learning environment. All children with learning disabilities will be socially disadvantaged in adulthood unless they are provided with opportunities for social integration, continuing education, skills training, employment and normal living facilities which meet their needs. Although there appears a logical shift in agencies' responsibilities as children with intellectual impairment progress through life, there is considerable diversity within this group and care can only be effectively provided on the basis of a sophisticated assessment of individual need and provision of integrated care. PMID- 7999379 TI - Is hospital the right place? A survey of 'inappropriate' admissions to an inner London NHS trust. AB - BACKGROUND: Acute hospital beds form an important health care resource. However, it is accepted that some beds may be used 'inappropriately' by patients who, although no longer requiring the facilities of an acute bed, cannot be discharged because of difficulties in organizing care at home or elsewhere. METHODS: Using the Oxford Bed Study Instrument, all admissions to an inner London NHS trust over a one-week period were classified as either appropriate or inappropriate. RESULTS: During the study week there were 689 in-patient admissions of which five were classed as inappropriate. Of the five inappropriate patients two were children and three were aged 65+. For one child the admission was for clear social reasons. However, the remaining four patients all presented a clear need for either respite or hospice care. Lack of provision of such facilities meant that they had to be admitted to an acute hospital bed. CONCLUSION: Overall our study highlighted the comparative rarity of inappropriate admissions, but did indicate that such patients may have long lengths of stay or repeated admissions which, as well as the amount of resources involved, prevent the bed from being used by other patients. PMID- 7999380 TI - Determinants of breastfeeding in Salisbury and Durham. AB - BACKGROUND: The practice of breastfeeding is related to socio-demographic characteristics: both show marked variation by place within the United Kingdom. This study set out to test the commonly held assumption that geographical variations in breastfeeding practices are explained by socio-demographic differences. METHODS: The mothers of 326 six-week-old babies living in Salisbury or Durham Health Districts were interviewed to determine attitudes to breastfeeding practice. RESULTS: More mothers in Salisbury breastfed than mothers in Durham, both immediately after birth (Salisbury 79 per cent, Durham 54 per cent) and at six weeks (50 per cent and 26 per cent). Higher rates of breastfeeding after birth were associated with higher level of qualification, encouragement to breastfeed antenatally and the mother having been breastfed herself. Higher rates at six weeks were associated with higher level of qualification, higher parity and willingness to breastfeed away from home. The differences between districts persisted after adjustment for these variables, but were diminished when willingness to breastfeed away from home was taken into account. CONCLUSION: Differences between the two districts in breastfeeding practice cannot be wholly explained by traditional socio-demographic characteristics, and may be related to local culture. Health education is unlikely to change breastfeeding practices unless prevailing cultural attitudes also change. PMID- 7999381 TI - Women who have abortions--are they different? AB - BACKGROUND: The aim of the study is to test the hypothesis that there is no difference between women who are currently undergoing an abortion and those who are not in an inner London health district. METHODS: One hundred and thirty-one consecutive attenders at an inner city day-care abortion service were compared, using a self-administered questionnaire, with two other groups: a random sample of 142 women aged between 18 and 45 taken from the local Family Health Services Authority age-sex register, and 149 consecutive attenders at the district's antenatal clinic. RESULTS: Women in the abortion group were found to be very similar to those in the antenatal sample in terms of social class, obstetric history, ethnic origin and knowledge of contraception. Women in the population survey, however, were found to be older, of higher social class, more likely to be white and of UK origin, and to have higher contraceptive knowledge scores. However, when the results were adjusted for age, the differences in social class and several other variables disappeared, although differences in ethnic origin remained. CONCLUSION: It was concluded that apart from age and ethnic origin, there were no differences between women who were having abortions and those who were not. The evidence points to abortion rates being a function of fertility rate, which is in turn a function of culture, rather than the results of the activities of individual or sub-groups of women at particular risk. PMID- 7999382 TI - Is there a market for regional units in child and adolescent psychiatry? AB - BACKGROUND: An analysis of the demand for the services of a sub-regional Family and Young Persons Unit which offers both in-patient and out-patient treatment for children and adolescents with psychiatric, emotional or psychological problems was performed. METHODS: Interviews were held and questionnaires were sent to representatives of the principal and potential users of the service both within the local district and beyond. RESULTS: The results demonstrated unmet demand for outpatient services but only limited demand for in-patient services in some districts. The role of market research in the new National Health Service and some of the difficulties of applying it are discussed. The implications of the findings for both the Family and Young Persons Unit and for child and adolescent psychiatry are considered. CONCLUSION: It is concluded that the effect of the market may be to bring about the closure of regional units unless there is intervention to protect them. PMID- 7999383 TI - General professional training in public health medicine--the Leicestershire Senior House Officer scheme. AB - BACKGROUND: This study investigates the subsequent careers of the Senior House Officers (SHOs) who have passed through the Leicestershire SHO training scheme in public health medicine since its inception in 1981 and their views of the scheme. METHODS: Postal questionnaires were sent to past and current SHOs, using addresses compiled from personnel records, the Medical Directory and the General Medical Council Medical Register. One reminder letter was sent to non-responders. RESULTS: Of the 21 past SHOs, one is now a consultant and four are currently trainees in public health medicine. Other past SHOs have followed diverse careers but the largest group are now in general practice. The four past SHOs who are now trainees in public health gained no further clinical experience before obtaining registrar or lecturer posts. All past SHOs responded favourably when asked about the benefits of the scheme regardless of their subsequent career choice. CONCLUSION: The continuing need for high-calibre recruits to the specialty and the favourable response from past SHO trainees suggests that this scheme, and no doubt other similar schemes, should be making their benefits known to a wider audience. PMID- 7999384 TI - Immunization uptake and parental perceptions in a strictly orthodox Jewish community in north-east London. AB - BACKGROUND: We wished to ascertain immunization uptake rates in the strictly orthodox Jewish community in Hackney and to survey reasons for non-uptake and attitudes to immunization and immunization services within this community. METHODS: A total of 575 strictly orthodox Jewish children, aged under 2.5 years, were identified from three general practices in the community, and a random sampling of 100 of these children was carried out. The sample uptake recorded by family doctors was compared with District uptake rates. A questionnaire was administered to parents. The main outcome measures were immunization uptake rate, reasons for non-uptake, and attitudes to immunization. RESULTS: Percentage immunization uptake (95 per cent confidence intervals) was: third diphtheria 86 per cent (82-90 per cent); third pertussis 82 per cent (78-86 per cent); and MMR 79 per cent (75-85 per cent). District uptake rates for a cohort of the same age, and at the time of the study, were: third diphtheria 82 per cent; third pertussis 79 per cent; and MMR 83 per cent. Sixty-seven parents completed the questionnaire (72 per cent response) and their children's uptake was the same as for children of nonresponders. All parents thought immunization to be important. CONCLUSIONS: For all immunizations, uptake in the strictly orthodox Jewish community is not significantly different from that of the District. Responding parents had positive attitudes to the value and safety of immunizations but wished better access to services. Health professionals need to question their perceptions so that efforts to improve uptake amongst ethnic minority groups are based on facts and are responsive to identified needs. PMID- 7999385 TI - General practitioner attitudes to day surgery. AB - BACKGROUND: Day surgery is increasing in importance. Unfortunately, its impact upon health professionals in the community is poorly documented. This paper reports the opinions of general practitioners (GPs) in a North Western Health District. METHODS: A structured attitude questionnaire was sent to all GPs in Trafford Health District. GPs were asked for their opinions of the relative merits of day and in-patient surgery for patients with similar conditions. Replies were received from 71 GPs, giving a response rate of 65 per cent. RESULTS: GPs gave only a mixed level of support to the idea of further expansion. This related less to considerations of workload in the Primary Care Team than it did to concerns about readmissions and complications. CONCLUSION: The further development of day surgery will require a greater sensitivity to the resource and information needs of professionals in the Primary Care Team. PMID- 7999386 TI - Heaven can wait. AB - The apparently unlimited demand for health care, finite supply of resources, the internal social market and continuous technological advances have given rise to increasing concern about the performance of health services. We examine an important measure of health care performance--avoidable mortality. Studies extending the scope of avoidable mortality and other outcome indicators are discussed. Although avoidable mortality is limited to providing a warning signal of possible health care deficiencies and is not an appropriate measure for all types of intervention, it still provides us with one of the best guides to the performance of health services. PMID- 7999387 TI - Improving the comparability of cancer registry treatment data and proposals for a new national minimum dataset. AB - BACKGROUND: There is no consistent or standardized practice for the collection of treatment data in UK cancer registries. This limits the usefulness and effectiveness of undertaking multiregional or national studies of treatment outcomes and survival. METHODS: A working group was established to examine the practices for recording the type and the amount of treatment data held in the cancer records at different registries. A common set of anonymized case notes for breast and colorectal cancer patients, drawn from each registry, was employed to eliminate any selection bias. Each registry coded these case notes according to their own criteria, and the comparability of such data between registries was determined from their returns. RESULTS: Of the 11 registries in England, seven participated in the full study, with a total of 84 records being submitted by five registries. A flow diagram was constructed to show how specific data items in the cancer record structure could be linked between registries. Errors or inconsistencies in recording treatment details were identified, and the constraints in data comparability were defined from the case note returns. CONCLUSION: Variations in coding practice between registries were such as to vitiate interregional or national comparisons of current data. The working group recommended an extended minimum dataset, which included a date for the start of each treatment modality, that most registries should be able to implement with some system changes. PMID- 7999388 TI - Piccadilly Circus legionnaires' disease outbreak. AB - BACKGROUND: An outbreak of legionnaires' disease occurred in central London in January and February 1989. An Infection Control Committee was established to investigate the outbreak and institute control measures. The objective of this paper is to describe the investigation and control of the outbreak. METHODS: An epidemiological survey and case-control study were carried out. The subjects were cases of community acquired pneumonia associated with central London with onset of illness in January and February 1989. RESULTS: Thirty-three confirmed cases, including five deaths, and ten suspected cases, including three deaths, were identified with dates of onset from 1 January to 11 February. A clustering of visits by cases to the vicinity of Piccadilly Circus was noted, and a case control study demonstrated a strong association between illness and visits to this area in the two weeks before onset of symptoms. The causative organism, Legionella pneumophila serogroup 1, was isolated from six patients. Legionella pneumophila of the same serogroup was isolated from water samples from five wet cooling systems (cooling towers) in the area under investigation, but in only two systems was the organism indistinguishable by subtyping from the patients' strains. Many of the cooling towers examined were inadequately maintained, including one of the two above a building adjacent to Piccadilly Circus from which a strain indistinguishable from the outbreak strain was isolated. All cooling towers in the area were shut down until inspected, and only allowed to restart after appropriate maintenance had been instigated. CONCLUSIONS: This outbreak showed the continuing risk of legionnaires' disease posed by wet cooling systems, including cooling towers, and highlighted the need to assess this risk so that appropriate maintenance is carried out. Regulations have recently been introduced, under the Health and Safety at Work Act, requiring notification of all wet cooling systems to the local authority to facilitate the investigation of outbreaks of legionnaires' disease. PMID- 7999389 TI - Social deprivation and age at presentation in amblyopia. AB - BACKGROUND: Amblyopia is the most common visual disability in children. Early treatment is thought to be more effective, and therefore factors affecting the age at presentation are important. A relationship between social deprivation and access to health care and screening services is well known. We hypothesized that social deprivation might be associated with later presentation of amblyopia, particularly of anisometropic amblyopia which depends on vision screening for referral. METHODS: Data from a historical cohort of 897 children with amblyopia, from seven UK orthoptic clinics, were used to test this hypothesis. Social deprivation was measured by the Townsend score of the ward in which the child lived. RESULTS: A relationship between social deprivation and age at presentation was found in children with anisometropic amblyopia even after adjusting for differences between clinics (p = 0.01) but no similar association was evident in children with amblyopia associated with strabismus. There was a difference of 22 months in the average age at presentation between children with anisometropic amblyopia in the most deprived and least deprived areas of the study. CONCLUSIONS: If screening for anisometropic amblyopia is to be undertaken, priority should be given to screening children from areas of social deprivation. PMID- 7999390 TI - Hepatitis B vaccination: how many doctors are fully covered? AB - Hepatitis B is an important health hazard to both health care workers and the patients they treat. Concerns over the safety of the original vaccine were reported in early studies as reasons for poor vaccine uptake amongst health workers. In this study, the overall uptake of a safe effective vaccine is still shown to be inadequate. However, a low perception of risk is the main reason stated for this behaviour. Needlestick injuries remain common, and a poor knowledge of action necessary is shown. A vaccine programme for junior housemen is shown to increase uptake substantially and is advocated for other grades. PMID- 7999391 TI - Quarterly communicable disease review January to March 1994. PHLS Communicable Disease Surveillance Centre. PMID- 7999392 TI - Antimalarial prophylaxis. PMID- 7999393 TI - Laser vaporization in the management of CIN. PMID- 7999395 TI - Non-notification of food poisoning--whose fault? PMID- 7999394 TI - Reasons for HIV diagnosis delay in Antwerp. PMID- 7999396 TI - Whistle-blowing. PMID- 7999397 TI - Death certification--a sad state of affairs. PMID- 7999398 TI - The importance of investigating chemical incidents. PMID- 7999399 TI - Aggressive non-Hodgkin's lymphoma in elderly patients: where to go from here? PMID- 7999400 TI - Renal cell cancer: is there long-term survival advantage from cytokine treatment? PMID- 7999401 TI - We still need common criteria for the assessment of nausea and vomiting. PMID- 7999402 TI - The effect of endocrine therapy on the levels of oestrogen and progesterone receptor and transforming growth factor-beta 1 in metastatic human breast cancer: an immunocytochemical study. AB - The levels of oestrogen receptor (ER), progesterone receptor (PR) and transforming growth factor-beta 1 (TGF-beta 1) were measured by immunocytochemistry in 19 patients prior to and 1 month after the start of endocrine therapy (tamoxifen 10 patients; aromatase inhibition 9 patients). A complete or partial response was observed in 10 patients. The proportion of cells showing ER staining was higher in responding patients, but there was no change observed with endocrine therapy in either responding or non-responding patients. In contrast, cells staining for PR in responding patients were significantly reduced following therapy (59 +/- 9% to 24 +/- 9%: P < 0.05). There was no reduction in immunocytochemical PR in non-responding patients, although the numbers of these patients with initially positive PR levels was small. Stromal tissue adjacent to tumour cells stained with the antibody to TGF-beta 1, with particularly intense staining at the periphery of tumour cell aggregates. There was no correlation between the degree of TGF-beta 1 staining and ER or PR status, and no evidence of a change with endocrine therapy. It is concluded that neither tamoxifen nor aromatase inhibitors produce a change in the ER content or TGF-beta 1 content of breast tumours as detected immunocytochemically, but PR levels are significantly reduced after therapy in responding patients. PMID- 7999403 TI - The roles of patient and observer assessments in anti-emetic trials. AB - The endpoints assessed by both patients and nurses were compared in three anti emetic studies. In a parallel subjects study, there was no significant difference between the patients' and nurses' assessment of the number of vomiting episodes, but the duration of vomiting, the severity and duration of nausea, and the side effects of the anti-emetic were given higher scores by the nurses. In two cross over studies, the patients recorded more vomiting episodes than the nurses, while the nurses recorded more anxiety and sedation than the patients. This resulted in the patients detecting a difference between the side-effects of the anti-emetics being compared that was not apparent from the nurses' forms. Many of the differences reflect differences in the timing and frequency of data collection. Nurses collected data regularly during the assessment period whereas patients reported their experiences only at the completion of 24 h. Both assessments provide useful perspectives on the study outcomes. PMID- 7999404 TI - A phase I/II study of the intralesional injection of ricin-monoclonal antibody conjugates in patients with hepatic metastases. AB - A phase I/II study of the intralesional administration of ricin-labelled monoclonal antibodies was conducted in patients with hepatic metastases of gastrointestinal origin. The anti-carcinoembryonic antigen (CEA) antibody I-1 was conjugated to blocked ricin via a disulphide bridge. After a test dose of antibody, patients were injected with ricin-antibody conjugates under computed tomography (CT) guidance on two occasions 1 week apart. Patients with stable or responding disease would receive a third course. The dose of ricin relative to surface area was increased in a predefined manner in cohorts of 3 patients. A total of 27 patients with hepatic metastases were entered into this study. All patients had metastatic colorectal cancer (26 patients) or adenocarcinoma of unknown primary with elevated CEA levels (1 patient). The presence of malignancy was documented cytologically in 9 of 11 patients tested. Minor responses were seen in 7 patients. However, no major objective responses or changes in the growth rate of injected lesions were observed. Toxicity was generally mild, the most common being hepatic capsular pain 24-48 h after each injection. 6 patients experienced rigors. One patient had anaphylaxis. Human anti-mouse and anti-ricin antibody responses were observed. Although substantial amounts of ricin conjugated to monoclonal antibodies were delivered into single lesions, this therapeutic approach was unsuccessful. Future studies of ricin-labelled antibodies should incorporate the systemic administration of immunoconjugates. PMID- 7999405 TI - Predictors of residual mass histology following chemotherapy for metastatic non seminomatous testicular cancer: a quantitative overview of 996 resections. AB - Following chemotherapy for metastatic non-seminomatous testicular cancer, surgical resection may demonstrate that residual masses contain purely benign tissue (necrosis), or potentially malignant tissues (histologically viable cancer cells or mature teratoma). The morbidity, mortality and costs of resection demand that resection is based on empirical data rather than on subjective judgements. We reviewed 996 resections from 19 studies to quantify predictors of the histology at resection. Predictors were analysed for each study and combined in a pooled odds ratio (OR). Predictors of necrosis were: (1) a teratoma-negative primary tumour (OR = 5.1); (2) normal tumour markers before chemotherapy [alpha fetoprotein (AFP): OR = 2.8; human chorionic gonadotrophin (HCG): OR = 1.9; both AFP and HCG: OR = 5.7]; (3) a smaller postchemotherapy abdominal mass (e.g. < or = 20 mm: OR = 3.7); (4) a large shrinkage (> or = 90%: OR = 3.1); (5) lung resections versus abdominal resections (OR = 1.7). Cancer was found in only 4% of residual retroperitoneal masses < or = 20 mm. Further research may combine the primary tumour histology, marker level and mass size to improve clinical guidelines, which define subgroups of patients for whom the benefits of resection do not outweigh the risks. PMID- 7999406 TI - Medical therapy of malignant nerve pain. A randomised double-blind explanatory trial with naproxen versus slow-release morphine. AB - It is uncertain whether there exists a nociceptive component in malignant nerve pain responsive to NSAIDs and opioids. 20 patients with malignant nerve pain were randomly assigned to treatment with naproxen 1500 mg versus slow-release morphine 60 mg daily during 1 week, followed by cross-over medication during the second week in a double-blind, double-dummy protocol. In the 16 evaluable patients, a significant (P < 0.05) reduction of 26% (S.E. +/- 7.9) in pain intensity was reached at day 7, compared to baseline pain. At day 7, significant pain relief of 32% (P < 0.05) was observed in the naproxen group, but not in the morphine group (21%, P = 0.14). Patients using morphine needed approximately twice as much paracetamol rescue than patients using naproxen. Additional pain relief could be observed in 4/9 patients with cross-over medication. These data support the concept of a nociceptive component in malignant nerve pain responding to NSAIDs and opioids, and favour the combination of both an anti-inflammatory drug and an opioid for symptomatic pain relief. PMID- 7999407 TI - Treatment of advanced colorectal cancer with folinic acid and 5-fluorouracil in combination with cisplatinum. AB - 51 patients with metastatic colorectal cancer (stage Dukes D) were treated with intravenous (i.v.) infusion on days 1, 3, 5, 8 and 16 with folinic acid (200 mg/m2) and 5-fluorouracil (600 mg/m2), and on days 1, 8 and 16 with cisplatinum (25 mg/m2 i.v.); cycles were repeated every 4 weeks. All 51 patients were evaluable for toxicity and response criteria. 26 patients had objective responses (3 complete responses, 5.9%; 23 partial responses, 45.1%), relative risk 51% (95% confidence intervals 36.7-65.0%). Response duration ranged from 4 to 28.0 months (median 16.8). Overall median survival of all patients included was 14.7 months (range 3.0-33.0). Toxicity of WHO grade III, requiring dose reduction, occurred in 9 (18%) patients. The regimen described here appears to be active, safe and well tolerated for treatment of patients with advanced colorectal cancer. PMID- 7999408 TI - Sex hormone levels in postmenopausal women with advanced metastatic breast cancer treated with CGS 169 49A. AB - 30 postmenopausal patients with metastatic breast cancer were treated with three different doses of fadrozole hydrochloride (CGS 169 49A), a non-steroidal competitive aromatase inhibitor. The effect of 0.5, 1 and 2 mg given twice daily upon the levels of oestrogens, their androgen precursors and upon the concentration of sex hormone binding globulin (SHBG) was investigated after 1 and 3 months and then every 3 months until progression of disease. A significant reduction in the serum concentration of oestrone (P < 0.0001) was obtained at all doses. Also, the serum concentration of oestrone sulphate was significantly reduced (P < 0.0001). However, after 1 month, the concentration was significantly different from pretreatment levels (P < 0.01) only at the 4 mg daily dose. A decline was also observed in the concentration of SHBG (P < 0.05), with a concomitant elevation of the percentage non-SHBG-bound oestradiol. The androgens, testosterone and dehydroepiandrosterone sulphate, were unaltered during treatment, while androstendione was significantly elevated at the 2 mg daily dose (P < 0.001). PMID- 7999409 TI - Serum levels of tumour necrosis factor-alpha in patients with B-cell chronic lymphocytic leukaemia. AB - Serum levels of tumour necrosis factor-alpha (TNF-alpha) have been evaluated in the peripheral blood of 91 patients with B-cell chronic lymphocytic leukaemia (B CLL), and have been correlated with the clinical stage (according to Rai's staging system) and relevant haematological and immunological data. Increased values were detected, compared to 36 normal age-matched controls (36 pg/ml +/- 5 versus 0.11 pg/ml +/- 0.08; P < 0.05). An increase of TNF-alpha serum levels was observed in all stages including stage 0, with a progressive increase in relation to the stage of the disease. A significant relationship between serum TNF-alpha levels and the number of circulating monocytes (P < 0.002) and an inverse correlation with the level of the haemoglobin (P < 0.001) was established, as defined by the Pearson's correlation test. In contrast, no correlation was observed between TNF-alpha serum levels and the other parameters taken into account, including the white blood cell and platelet counts, the absolute number of peripheral blood (PB) lymphocytes, CD5+ B lymphocytes, CD57+ lymphocytes, serum levels of lactic dehydrogenase, total serum immunoglobulins and the serum levels of IgG, IgA and IgM. These data suggest that, in addition to the B-CLL neoplastic cells, the PB monocytes may be involved in the release of TNF-alpha. PMID- 7999410 TI - Efficacy of combined 5-fluorouracil and cisplatinum in advanced gastric carcinomas. A phase II trial with prognostic factor analysis. AB - Combined chemotherapy has demonstrated a degree of efficacy in gastric carcinoma. As 5-fluorouracil (5FU) and cisplatinum are two of the most active drugs, we have tested the efficacy of combined 5FU and cisplatinum in a prospective phase II trial. Cycles were administered every 4 weeks and consisted of 5FU 1000 mg/m2/day 5 days continuous intravenous (i.v.) infusion and cisplatinum 100 mg/m2 on day 2. Cycles were repeated according to tolerance and efficacy. 87 patients entered the study, 57 with metastatic or recurrent tumour (M) and 30 with locally advanced gastric cancer (LAGC). The response rate for the 83 evaluable patients was 43% [95% confidence interval (CI) 30-56%]. There were four complete responses (5%), 32 partial responses (39%), 34 cases of stable disease and 13 cases of progressive disease. Responses were more frequent in patients with a good performance status (P = 0.02), with their primary located in the cardia (P = 0.003), with a non-linitis plastica tumour form (P = 0.003) or a tumour containing less than 50% of independent cells (P = 0.016). Median survival was 9 months for the total population. It was better in patients with a good performance status (P = 0.01), and those who did not have linitis plastica (P = 0.005). Toxicity was acceptable, although grade 3-4 neutropenia was reported in 22% of the cycles, mucositis in 14% and 3 patients died of septic complications. The combination of 5FU and cisplatinum is effective in terms of tumour response in advanced gastric cancer and warrants testing with the other active regimens. PMID- 7999412 TI - Alteration of coagulation and fibrinolysis systems after multidrug anticancer therapy for lung cancer. AB - Recently, an increased frequency of thromboembolic events has been reported after the administration of anticancer drugs. The precise mechanism by which these vascular phenomena occur is unknown. The current work aims at evaluating the alterations of the coagulation and the fibrinolysis systems during the administration of antineoplastic agents by means of newly developed markers of haemostasis. This investigation comprised 25 lung cancer patients treated with multidrug combination chemotherapy. D-dimer, plasmin-alpha 2-antiplasmin complex, fibrin degradation products, fibrinogen, antithrombin III, thrombin-antithrombin III complex, prothrombin time and activated partial thromboplastin time were measured from samples taken before and on days 2, 5, 7, 14 and 21 after the administration of antineoplastic drugs. A significant reduction in plasma concentration of fibrinolytic activity markers, DD and PAP, was observed on days 5 and 7, and on days 2, 5, 7 and 14, respectively, following the administration of chemotherapeutic drugs. Statistically significant shortening of PT and APTT on days 2, 5, 7 and 14, as well as significant elevation of the thrombin generation marker TAT were observed on days 5 and 7 after chemotherapy. These results show that relatively higher levels of coagulation activation and a lower fibrinolytic activity occur during cytotoxic drug therapy compared with basal values. Small variations of haemostatic values and a short follow-up period may explain why no thrombotic events were observed during this study. Although further studies must be done to clarify these findings, the results of this investigation suggest that an imbalance of the coagulation-fibrinolysis system might be a contributing factor in the pathogenesis of thrombotic complications during chemotherapy. PMID- 7999411 TI - Neoadjuvant chemotherapy in locally advanced gastric carcinoma--a phase II trial with combined continuous intravenous 5-fluorouracil and bolus cisplatinum. AB - Locally advanced gastric adenocarcinomas (LAGC) have a poor prognosis, particularly when tumours are bulky, located in the cardia or in the event of locoregional lymph node involvement. Patients bearing these tumours were entered in a phase II trial of neoadjuvant chemotherapy, combining continuous intravenous 5-fluorouracil (5FU) (1000 mg/m2 for 5 days) and cisplatinum (CDDP) (100 mg/m2 on day 2) repeated every 4 weeks, for one to six cycles according to response and tolerance. 30 patients have been entered, 26 after clinical evaluation (CAT scan and upper gastrointestinal endoscopy) and 4 with unresectable tumours at prior laparotomy. Median age was 60 years, 15/30 patients had a tumour of the cardia, 15/30 had enlarged lymph nodes and 7/30 had linitis plastica (diffuse type). A mean number of three cycles was administered (range 1-6). 27 of the 30 patients were evaluable for response. One patient achieved a complete response (CR) and 14 a partial response (56%; 95% confidence interval 38-74%). No patient had tumour progression, and only 1/6 with linitis plastica responded. 28 patients underwent surgery, and 23 had a macroscopically complete resection (77% of the 30 entered patients); RO resections were performed in 60% of the cases, mainly after an objective response (13/15 versus 4/12 in nonresponders). No pathological CR were seen. Grade 4 neutropenia was observed in eight cycles (5 patients), with five septic complications and one death due to toxicity. Four postoperative complications were observed: 2 cases of severe pneumonia and 2 subphrenic abscesses. One postoperative death, due to intravascular disseminated coagulation, was observed at day 30. Median survival was 16 months and the 1-, 2- and 3-year survival was 67, 42 and 38%, respectively. Patients with linitis plastica had a significantly shorter survival (P < 0.002). We conclude that neodjuvant chemotherapy is feasible in LAGC, although randomised trials are warranted to demonstrate its efficacy on survival and resection rates. PMID- 7999413 TI - Pharmacokinetics of folinic acid and 5-methyltetrahydrofolic metabolite after repeated oral administration of calcium folinate following methotrexate treatment. AB - The pharmacokinetic profiles of folinic acid (FA) and its active metabolite, 5 methyltetrahydrofolic acid, were studied after oral administration of decreasing doses of calcium folinate during 37 courses of high and intermediate dose methotrexate treatment in 25 lymphoma patients. FA was administered at a dose of 6 x 50 mg in 15 courses, 6 x 25 mg in seven courses, 6 x 15 mg in 10 courses and 6 x 7.5 mg in 5 courses. FA, 5-methyltetrahydrofolic acid, methotrexate and 70H methotrexate were assayed simultaneously by high performance liquid chromatography. When FA was administered at doses between 50 and 15 mg, maximum concentrations of both the drug and its metabolite were always obtained after 1 to 2 h and remained stable. The same was true for the equilibrium concentration of the two products at doses over 15 mg. These findings suggest saturation of absorption and metabolism of folinic acid at doses over 15 mg. PMID- 7999414 TI - Phase II trial of high-dose epirubicin and cyclophosphamide in advanced breast cancer. AB - Between February 1990 and December 1991 high-dose epirubicin (Epi)(120 mg/m2) plus cyclophosphamide (CTX)(600 mg/m2) were given every 3 weeks to 52 patients with locally advanced and metastatic breast cancer. 26 patients with locally advanced disease received four courses of this regimen before and after local treatments. 26 patients had metastatic disease: they received eight courses unless progression or unacceptable toxicity occurred. Responses were seen in 37/48 (77%) evaluable patients including 14 complete responses (CR), 23 partial responses (PR), nine stable disease, two progressive disease. Among the 25 evaluable patients with locally advanced disease, 9 had a CR and 11 a > 80% decrease in tumour volume. 6 patients (24%) had a pathologically confirmed complete response. 18 patients (72%) had a tumour reduction to 0-2 cm. The 3-year disease-free survival was 60%. Of the 23 evaluable patients with metastatic disease, 5 obtained a CR and 10 a PR, yielding an overall response rate of 65%. Myelosuppression was substantial with a grade 3-4 leucopenia in 76% of the patients even if neutropenic fever occurred in only 7% of the courses. A clinical congestive heart failure occurred in 1 patient following a total Epi dose of 960 mg/m2 and a bilateral quadrantectomy and radiotherapy. We conclude that (1) high dose Epi + CTX is a very active regimen, in particular for the patients with locally advanced breast cancer; (2) breast conservation after this regimen in some of these patients may be considered; (3) neutropenia is the dose-limiting toxicity. Currently, a phase II study using the same combination given every 2 weeks together with r-methuG-CSF is ongoing. PMID- 7999415 TI - Serum erythropoietin levels in patients with solid tumours. AB - Patients with malignant disease frequently develop anaemia. To investigate the role of erythropoietin (EPO) in this anaemia, serum levels were determined in patients with solid tumours. The study population consisted of 84 patients (44 males, 40 females) with solid tumours and 99 healthy control subjects, and 13/84 patients were anaemic. Serum EPO was clearly elevated in the anaemic tumour patients, but this increase was less than in patients suffering from iron deficiency anaemia. As in iron deficiency anaemia, the correlation between EPO levels and haemoglobin values was inverse. When compared to healthy control subjects, the levels of EPO in the tumour patients without anaemia were decreased. We conclude that there may be an inhibition in the expression or secretion of EPO in patients with solid tumours which, as yet, has not been further defined. Based on this, the treatment of anaemia in cancer patients with erythropoietin appears promising. PMID- 7999416 TI - Treatment of advanced renal cell cancer with sequential intravenous recombinant interleukin-2 and subcutaneous alpha-interferon. AB - Starting from in vitro studies suggesting synergistic antitumour activity against renal cell cancer (RCC) of recombinant interleukin-2 (rIL-2) and alpha-interferon (IFN), a phase II trial was initiated to test the clinical activity of this combination. The two cytokines were administered sequentially, with the aim of reducing the risk of additive toxicity and enhancing the immunological reaction against the tumour. The original treatment schedule consisted of rIL-2 18 x 10(6) U/m2/day by continuous intravenous infusion for 120 h days 1-5, and alpha-IFN 2b, at a flat dose of 9 x 10(6) U by subcutaneous or intramuscular injection thrice in a week, from day 8 to 28. Treatment was planned to be continued for six or more 28-day cycles, depending on clinical response. 12 patients were treated according to this schedule; as some cardiovascular toxicity was experienced in this set of patients, 11 further patients were treated with half-dose rIL-2 (i.e. 9 x 10(6) U/m2/day). 17 out of 23 enrolled patients completed at least one cycle of treatment and were evaluated for response. We observed six major responses [one complete response (CR) + five partial responses (PR)] for an objective response rate of 35% [95% confidence interval (CI) 17-59%]. 5 additional patients achieved stabilisation of disease; one of them reached CR after surgical extirpation of a lung mass. Sites of response included lung, nodes and bone. Duration of response is 12+ months for CR; 17, 16, 12+, 9 and 9 months for PRs. Median survival is 16 months. Response was not significantly different between full-dose and half-dose rIL-2. Considering stable disease (SD) as responses, there seemed to be a higher chance of response for patients with smaller tumour burden (P = 0.032). The toxicity of rIL-2 treatment, mainly cardiovascular, was substantial; 9 patients experienced severe cardiotoxicity, consisting of major arrhythmias, myocardial ischaemia, reduction of ejection fraction measured with heart radionuclide scan, and were excluded from continuing treatment. Other rIL-2 related toxicities forcing exclusion from the study were severe thrombocytopenia (1 case), and generalised exfoliative dermatitis requiring steroids (1 case). Otherwise, treatment was well tolerated; rIL-2-related toxicities promptly recovered after rIL-2 discontinuation in the majority of cases, and no treatment related deaths were reported. The half-dose rIL-2 regimen was significantly less toxic in terms of hypotension (P = 0.014), fever (P = 0.014), oliguria (P = 0.042), serum creatinine elevation (P = 0.009) and prothrombin time elongation (P = 0.038).(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 7999417 TI - Delayed diagnosis and large size of breast cancer after a false negative mammogram. AB - The aim of this prospective, multicentre study was to investigate the effects of a false negative mammogram on treatment delay and tumour size. Among 306 consecutive women with histologically diagnosed, invasive breast cancer, the frequency of a false negative mammogram was small (13%) among women aged over 50 years, but 35% among those aged 50 or younger (P < 0.0001). Forty-five per cent of the women with a false negative mammogram had a longer than 2-month and 29% a longer than 6-month interval from mammography to surgery as compared with only 2 and 0% of women, respectively, who had a true positive mammogram (P < 0.0001 for both). Women with a false negative mammogram and a longer than 2-month interval to surgery had larger primary tumour size (60 versus 26% pT2-4, P = 0.005) and more often positive axillary nodes (60% versus 32% pN+, P = 0.03) at the time of surgery than those with a shorter delay. We conclude that a false negative mammogram is common in women younger than 50, and may lead to treatment delay and advanced clinical stage. PMID- 7999418 TI - Plasminogen activators and plasminogen activator inhibitors in blood and tumour fluids of patients with ovarian cancer. AB - We quantitated urokinase and tissue plasminogen activator (u-PA, t-PA), plasminogen activator inhibitor 1 and 2 (PAI-1, PAI-2), and fibrinolytic activity in peripheral blood (PB), tumour blood (TB), peritoneal/ascitic fluid (PAF) and cystic fluid (CF) from 104 patients with benign and 36 patients with malignant ovarian tumours, and in peripheral blood from 62 healthy controls. PB levels of u PA were higher in patients with benign and malignant tumours than in controls. High concentrations of u-PA were found in CF, but not in TB, suggesting that u-PA is released by the tumour tissue, but not by the tumour vasculature. PB levels of t-PA were higher in both tumour groups than in controls. Increased levels of t-PA were found in TB, but not in CF, indicating that t-PA is released by the tumour vasculature, but not by the tumour tissue. PB levels of PAI-1 were higher in patients with both benign and malignant tumours than in controls. High levels of PAI-1 were present in both TB and CF from malignant tumours, suggesting that PAI 1 is released from the tumour vasculature as well as the tumour tissue. Elevated concentrations of PAI-2 were found in CF, but not in TB, indicating release from the tumour tissue, but not from the vasculature. High levels of t-PA, PAI-1 and PAI-2 were found in PAF of malignant tumours, and resorption from this compartment may explain elevated PB levels in patients with ascites. None of the PAs/PAIs proved useful as a PB marker for detection of early stage ovarian cancer. However, an index based on PAF levels of t-PA and PAI-1 discriminated between malignant and benign ovarian cysts in the absence of ascites. In addition, our study stresses the importance of including patients with benign tumours as well as healthy controls when markers for malignant tumours are evaluated. PMID- 7999419 TI - Prognostic factors and survival in patients with metastatic renal cell carcinoma treated with chemotherapy or interferon-alpha. AB - Prognostic factors and survival were analysed in 295 patients with metastatic renal cell carcinoma (MRCC), treated with either chemotherapy (1975-1990) or interferon (IFN) (1983-1990). The 3-year survival was 8 and 24% in the chemotherapy and IFN groups, respectively (P < 0.001). In the univariate analysis, age < or = 60 years, prior nephrectomy, more than 1 year since initial diagnosis and treatment for metastatic disease, ECOG performance status 0 or 1, absence of liver metastases, lower erythrocyte sedimentation rate (first hour), and < or = 10% weight loss, within the past 6 months, were correlated with improved survival. Sedimentation rate, performance status and weight loss remained independent prognostic factors from the results of a Cox regression analysis. Three prognostic groups were identified from a combination of these factors. In the poor and intermediate risk groups, no significant survival difference was observed between patients treated with chemotherapy and those treated with IFN. The 3-year survival estimates for good risk patients were 15 and 48% in the chemotherapy and IFN groups, respectively. Therefore, in MRCC, sedimentation rate, performance status and weight loss are easily assessable and reproducible prognostic variables for the identification of risk groups. We hypothesise that IFN may increase survival in good risk patients, but is as ineffective as chemotherapy in poor risk patients with MRCC. PMID- 7999420 TI - O6-alkylguanine-DNA alkyltransferase activity in schistosomiasis-associated human bladder cancer. AB - O6-Alkylguanine-DNA-alkyltransferase (ATase) activity was measured in extracts of 55 bladder tissue samples (46 tumour and nine uninvolved mucosal tissue) from Egyptian patients with schistosome-associated bladder carcinoma. Activity varied from 2.0 to 16.2 fmole ATase/microgram DNA (mean +/- S.D.; 5.6 +/- 4.0) or from 28 to 351 fmole ATase/mg (117 +/- 71). ATase levels in schistosome-associated bladder cancer tissues (5.6 +/- 4.0 fmole ATase/microgram DNA) tended to be lower than those observed in normal human bladder mucosal tissue (8.5 +/- 4.4 fmole ATase/microgram DNA). In a previous study (Badawi et al., Carcinogenesis, 1992, 13, 877-881) DNA-alkylation damage (O6-methyldeoxyguanosine) was found in 44/46 of these schistosome-associated bladder cancer samples at levels ranging from 0.012 to 0.485 mumole O6-MedG/mole deoxyguanosine. We now report an inverse correlation between the levels of methylation damage and ATase activity (r = 0.67; P < 0.001). These observations encourage further investigations of the possible role of environmental alkylating agents in the aetiology of early bladder cancer associated with schistosomiasis. PMID- 7999421 TI - The Memorial Symptom Assessment Scale: an instrument for the evaluation of symptom prevalence, characteristics and distress. AB - The Memorial Symptom Assessment Scale (MSAS) is a new patient-rated instrument that was developed to provide multidimensional information about a diverse group of common symptoms. This study evaluated the reliability and validity of the MSAS in the cancer population. Randomly selected inpatients and outpatients (n = 246) with prostate, colon, breast or ovarian cancer were assessed using the MSAS and a battery of measures that independently evaluate phenomena related to quality of life. Symptom prevalence in the 218 evaluable patients ranged from 73.9% for lack of energy to 10.6% for difficulty swallowing. Based on a content analysis, three symptoms were deleted and two were added; the revised scale evaluates 32 physical and psychological symptoms. A factor analysis of variance yielded two factors that distinguished three major symptom groups and several subgroups. The major groups comprised psychological symptoms (PSYCH), high prevalence physical symptoms (PHYS H), and low prevalence physical symptoms (PHYS L). Internal consistency was high in the PHYS H and PSYCH groups (Cronback alpha coefficients of 0.88 and 0.83, respectively), and moderate in the PHYS L group (alpha = 0.58). Although the severity, frequency and distress dimensions were highly intercorrelated, canonical correlations and other analyses demonstrated that multidimensional assessment (frequency and distress) augments information about the impact of symptoms. High correlations with clinical status and quality of life measures support the validity of the MSAS and indicate the utility of several subscale scores, including PSYCH, PHYS, and a brief Global Distress Index. The MSAS is a reliable and valid instrument for the assessment of symptom prevalence, characteristics and distress. It provides a method for comprehensive symptom assessment that may be useful when information about symptoms is desirable, such as clinical trials that incorporate quality of life measures or studies of symptom epidemiology. PMID- 7999422 TI - Non-Hodgkin's lymphoma in elderly patients: a phase II study of MCOP chemotherapy in patients aged 70 years or over with intermediate- or high-grade histology. AB - During the period 1 January 1988 to 31 July 1991, 74 patients were seen with intermediate- or high-grade non-Hodgkin's lymphoma who were aged 70 years or over. Of these 74 patients, 20 were treated with radiotherapy alone, and 46 were judged as suitable for treatment with the chemotherapy regime MCOP (mitoxantrone, cyclophosphamide, vincristine and prednisolone). Involved field radiotherapy (35 40 Gy in 20 fractions over 4 weeks) was given to 14 of the 21 patients with stage IA and IIA disease, and 6 of the 25 patients with stage III and IV disease after completion of chemotherapy. The complete response rate was 63% at the completion of all treatment (6 months), and 39% at 12 months. There were no treatment related deaths, and the 3-year cause-specific survival was 26% (overall survival 21%). For patients aged 70-75 years, the 3-year cause-specific survival was 34% in comparison to 17% for those patients aged 76-93 years. The chemotherapy was well tolerated by those patients aged 70 years and over, 70% of the patients did not vomit and no patients had significant vincristine neuropathy. There were only four infections associated with neutropenia. All patients completing six cycles had moderate, patchy alopecia. This MCOP regime is suitable for patients aged 70 years and over with intermediate- and high-grade non-Hodgkin's lymphoma. The survival of patients is comparable to that obtained with CHOP (cyclophosphamide, doxorubicin, vincristine and prednisolone) with less apparent toxicity. PMID- 7999423 TI - Long-term survival after chemotherapy containing platinum derivatives in patients with advanced unresectable non-small cell lung cancer. European Lung Cancer Working Party. AB - The study set out to determine the rate of long-term survivors (LTS) in patients treated with platinum-containing chemotherapy for advanced non-small cell lung cancer (NSCLC), to identify prognostic factors predicting long-term survival (> or = 2 years) and to report the LTS natural history. Eligible patients with advanced NSCLC treated by chemotherapy in one of seven trials conducted by the European Lung Cancer Working Party from December 1980 to August 1991 were included. All patients received cisplatin and/or carboplatin. Of these, 1052 patients were eligible and 24 variables were analysed as potential prognostic factors. Actuarial 2-year and 5-year survival rates were, respectively, 7.4 and 1.8%. All patients surviving for > or = 5 years had limited disease and were treated by complementary chest irradiation and/or surgery. Univariate prognostic factor analysis for LTS identified as significant no major weight loss, limited disease, no liver metastases, normal white blood cells and neutrophils and normal lactic dehydrogenase levels. By multivariate analysis, the only significant factor was limited disease. Objective response to chemotherapy was also found to be, as disease extent, a highly significant predictor for LTS. Thus, the two best prognostic factors for LTS were non-metastatic disease and response to chemotherapy. PMID- 7999424 TI - Timing of surgery influences survival in receptor-negative as well as receptor positive breast cancer. AB - Analysis of oestrogen and progesterone receptor (ER, PR) status was interpreted in relation to menstrual phase at the time of surgery and survival in 84 women diagnosed with breast cancer between 1975 and 1988. We showed previously (Br J Surgery 1994, 81, 217-220) that long-term survival was significantly poorer when surgery was performed during the follicular phase of the menstrual cycle compared to luteal phase; we now demonstrate that this effect on survival is at least as important in receptor-negative as receptor-positive patients. At 10 years, overall survival (OS) of ER-positive patients who had their biopsy during the follicular phase was significantly poorer than for those whose biopsy was performed during the luteal phase of their menstrual cycle (52 versus 88%, P = 0.02). OS for the ER-negative follicular phase group was also significantly poorer than that for the ER-negative luteal phase group (33 versus 76%, P = 0.009). The OS difference between the PR-positive follicular phase group and PR positive luteal phase group was of borderline significance (60 versus 87%, P = 0.06), while the difference in OS between the PR-negative follicular phase group and that of the PR-negative luteal phase group was highly significant (13 versus 76%, P = 0.001). Disease-free survival for these groups followed a similar trend. The survival differences in receptor-negative women suggest that hormonal fluctuations at the time of surgery may have complex indirect effects on tumour growth and metastasis. The mechanism, if indeed independent of the tumour steroid receptors, could also apply in other cancers. PMID- 7999426 TI - A comparison of rhodamine 123 accumulation and efflux in cells with P glycoprotein-mediated and MRP-associated multidrug resistance phenotypes. AB - Rhodamine 123 (Rh123) is a fluorescent dye which locates in the mitochondria of cells. It is a substrate for P-glycoprotein (Pgp) and can, therefore, be used as a molecular probe in studies of the multidrug resistance (MDR) phenotype. However, not all MDR cells overexpress Pgp. In some, the MDR phenotype is associated with expression of an alternative transporter molecule, the multidrug resistance-associated protein (MRP). We have studied the accumulation and efflux of Rh123 in MDR cells having both Pgp-mediated and MRP-associated phenotypes. In the mouse tumour parental cell line, EMT6/P, Rh123 accumulates rapidly to reach plateau levels by 90 min. Confocal microscopy confirms a localisation to the mitochondria. In the MDR subline, EMT6/AR1.0, which overexpresses Pgp and which is 10-fold resistant to Rh123 cytotoxicity, accumulation is dramatically reduced. Efflux of Rh123 from both resistant and parental lines is rapid but can be inhibited by reduced temperature or by the presence of cyclosporin A (5 micrograms/ml). Efflux from the parental line is probably due to the presence of very low, but detectable, levels of Pgp but the existence of other mechanisms cannot be ruled out. In contrast, the human lung cancer parental cell line COR L23/P, and its MRP-associated (but Pgp-negative) MDR subline, COR-L23/R (which is 23-fold resistant to Rh123 cytotoxicity), accumulate Rh123 at similar rates for the first 30 min. The curves then diverge so that, at 180 min, the resistant cells contain only 70% of the Rh123 of parental cells. Confocal microscopy demonstrates a similar distribution of fluorescence in resistant and parental cells. Essentially no efflux of Rh123 occurs from parental cells, whereas 70% of the content is lost from resistant cells over a period of 150 min. Such efflux may again be inhibited by reduced temperature but cyclosporin A (5 micrograms/ml) has little effect. These observations should be borne in mind when interpreting Rh123 efflux data in terms of MDR mechanisms. PMID- 7999425 TI - Evidence for a growth effect of epidermal growth factor on MDA-MB-231 breast cancer cells. AB - MDA-MB-231 is a breast epithelial cell line which possesses large amounts of epidermal growth factor (EGF) receptor on its cell surface but does not respond to EGF under standard culture conditions. 8-bromo-cyclic AMP (8Br-cAMP) and cholera-toxin treatments inhibit its growth by increasing its intracellular cAMP level. However, when inhibited in this way, MDA-MB-231 remains unresponsive to EGF. Similar effects--cAMP accumulation and inhibition of cell growth--are produced by forskolin. In addition, this substance specifically blocks MDA-MB-231 cells in G1 phase of the cell cycle. EGF is able to reverse the effect of forskolin on cell proliferation and prevents accumulation of cells in G1 phase without any change of cAMP level. Thus, only when inhibiting cell growth with forskolin does a mitogenic effect of EGF become evident. As cAMP is increased to a similar degree by all three compounds, yet only the effect of forskolin is antagonised by EGF, we suggest that a non-cAMP-mediated effect of forskolin must be considered to explain this effect. In contrast, the mitogenic effect of EGF on the NPM14T4/9 breast epithelial cell line does not change in the presence of forskolin. PMID- 7999428 TI - Measurement of radiation survival using the MTT assay. AB - There is increasing interest in the development of rapid assays of radiosensitivity which can be used on clinical specimens. Unfortunately, the measurement of radiation survival using clonogenic assays, which are the established standard, can be difficult and time consuming. We have used the MTT assay to measure the radiation survival of four lymphoblastoid cell lines with low plating efficiencies. We measured surviving fractions both when the irradiated cells had regained exponential growth and when the non-irradiated cells had undergone four or more doublings. The results were compared to surviving fractions measured by clonogenic assay. We found both methods could be used successfully to rank the cell lines in order of radiosensitivity. However, cells exposed to the higher radiation doses in the MTT assay did not always regain exponential growth, limiting the dose range for which the assay was useful. We also found the best correlation between the two assays was sometimes obtained by using the MTT surviving fractions from different days for different radiation dose levels. Thus, although the MTT assay can be used to measure radiation survival in relation to other cell lines, its use can be complicated by restrictions on radiation dose ranges and difficulties with data interpretation. PMID- 7999427 TI - Radiosensitivity of new and established human melanoma cell lines: comparison of [3H]thymidine incorporation and soft agar clonogenic assays. AB - Seven new low-passage melanoma lines were developed in this laboratory from clinical melanoma specimens and characterised for chromosome complement, DNA ploidy and S-phase content. The radiosensitivity of these lines was compared with that of eight established melanoma cell lines, FME, MM-96, SK-MEL-5, SK-MEL-28, SK-MEL-2, MALME-3M, M19-MEL and LOX-IMVI, using a 96-well microculture assay technique. Dose-response curves were determined using a 5-day incubation period and 6-h terminal [3H]thymidine-labelling period. Radiation (60Co source) was carried out under a lead wedge to provide a radiation dose range of 0-10 Gy, or by irradiating part of the plate (radiation dose 0 or 2 Gy). Data for a range of cell densities in a single 96-well plate were combined into a single regression equation incorporating linear quadratic terms for radiation dose and cell density. SF2 values were defined as the amount of thymidine incorporated following a radiation dose of 2 Gy, expressed as a fraction of that of unirradiated cells, and varied from 0.36 to 0.93. The reproducibility in repeat assays, as defined by the standard error of determinations at different passage numbers, was +/- 0.04. The newly developed lines exhibited a similar range of radiosensitivity to that of the established lines, and melanin content did not correlate with resistance. For nine of the lines, radiation parameters were also determined using a modified Courtenay clonogenic soft agar assay technique, and the results compared with the thymidine incorporation results, and a significant linear correlation was found between SF2 and SF2' (r = 0.89). The linear (alpha) and quadratic (beta) terms of the best-fit linear quadratic dose-response curves, were significantly correlated between the two assays. It is concluded for this series of human melanoma lines that proliferation assays in 96-well plates provide radiosensitivity parameters comparable to those using clonogenic assays. PMID- 7999429 TI - The genetics of familial breast cancer and their practical implications. AB - A small proportion of breast cancer (perhaps about 5%) and a higher proportion of early onset cases are due to the inheritance of mutations in dominant susceptibility genes which confer a high lifetime risk of the disease. This would equate to about 1250 cases per year in the U.K. and 9000 in the U.S.A. Even within these cases, there is genetic heterogeneity, i.e. there are several genes involved, each giving rise to different patterns of other cancers associated with the familial breast cancer. One such gene (p53) has been identified and a second (BRCA1) has been precisely mapped in the human genome, but further breast cancer predisposition genes remain to be identified. In addition, there are other genes which confer a lower risk of the disease, but may account for a larger proportion of cases, the most important example to date being ataxia telangiectasia. The identification of these genes will enable the entity of familial breast cancer to be more precisely defined and has implications for management of gene carriers with breast cancer and their relatives who are at risk. A major consideration in this new area of cancer genetics is that the identification of gene carriers may become possible on a large scale and this raises ethical and social issues. PMID- 7999430 TI - European Pancreatic Cancer Reference Library System, EPCRLS. PMID- 7999431 TI - The prognostic value of cell proliferation in non-small cell lung cancer assessed with tritiated thymidine and anti-PCNA antibodies. PMID- 7999433 TI - An erythropoietin-producing endometrium carcinoma. PMID- 7999432 TI - Sialyl-Tn expression in gastric carcinoma. PMID- 7999434 TI - Adhesion to type V collagen and cloning efficiency in agar of 8701-BC breast cancer cells. PMID- 7999435 TI - Intracranial germ cell tumours presenting with hypopituitarism. Successful treatment with chemotherapy alone. PMID- 7999436 TI - Epirubicin, cisplatin and intermittent continuous infusion of 5-fluorouracil in advanced gastric cancer: an effective regimen? PMID- 7999437 TI - Non-AIDS-related Kaposi's sarcoma in Florence, Italy (1985-1989) PMID- 7999438 TI - [Glutamate receptors]. PMID- 7999439 TI - [Intracranial tumors and T lymphocytes]. PMID- 7999440 TI - [MRI of paraventricular white matter lesions in amyotrophic lateral sclerosis- analysis by diffusion-weighted images]. AB - Magnetic resonance images in some cases of amyotrophic lateral sclerosis (ALS) revealed abnormal signals in both the paraventricular white matter and in the posterior limbs of the internal capsule. We examined T2- and diffusion-weighted MR images of these lesions in 18 cases of ALS. There were symmetrical high-signal areas in the posterior limbs of the internal capsule in all of the cases. The high-signal areas in the internal capsule corresponded to the pyramidal tracts in the anatomical atlas by Talairach. In 5 of the cases of ALS, T2- weighted MR images showed discrete paraventricular white matter lesions as well. The mean age of the ALS patients with paraventricular white matter lesions was higher than that of the ALS patients without such lesions. Proton densities calculated from the conventional MR images were higher in both the capsular and paraventricular lesions. The diffusion coefficients perpendicular to the pyramidal tract in the internal capsula lesions were within the normal range, where as the diffusion coefficients in the paraventricular lesions were increased in all directions. Thus, diffusion anisotropy was lost in the paraventricular lesions. These findings are similar to those observed in the white matter lesions of cerebro vascular origin. As a result, the pathology of the paraventricular lesions in ALS was confirmed to be different from that of the internal capsular lesions. PMID- 7999441 TI - [Protective effect of tetramethylpyrazine on ischemic neuronal damage in the gerbil hippocampus]. AB - The effect of tetramethylpyrazine on ischemic neuronal damage was studied in gerbil hippocampus in the terms of histopathological change and cerebral tissue lipid peroxides. Fifteen-five Mongolian gerbils were randomly assigned to one of three groups: sham-operated as control, subjected to 12 min global cerebral ischemia followed by 7 day spontaneous circulatory reperfusion, in which animals were treated with either ip. physiological saline or 60 mg/kg of tetramethylpyrazine 30 min before ischemia and daily thereafter for 7 days. The number of survival pyramidal neurons in the CA1 was counted: 263 +/- 8 (cell/mm) in the sham-operated group, 20 +/- 6 in the ischemia group, and 189 +/- 56 in the group treated with tetramethylpyrazine. Changes in lipid peroxides, expressed as malondialdehyde (MDA), was 134.5 +/- 5.0 nmol/g tissue in the sham-operated group, 193.5 +/- 5.1 in the ischemia group, and 137.6 +/- 10.8 in the group treated with tetramethylpyrazine. These results indicate that tetramethylpyrazine has a protective effect on the ischemic neuronal damage in hippocampus. Free radicals and free calcium may play an important role in pyramidal neuron necrosis in hippocampus following cerebral ischemia. PMID- 7999442 TI - [Sequential change of cerebral angiography in a case of cerebral angiitis following herpes zoster ophthalmicus]. AB - Delayed neurological symptoms and signs following herpes zoster ophthalmicus (HZO) such as "Delayed contralateral hemiplegia with HZO" are supposed to be due to ipsilateral intracranial angiitis and ischemic disorder. We experienced a rare case with ipsilateral cerebral hemorrhage following HZO. Under the diagnosis of cerebral angiitis associated with HZO, we treated her conservatively and observed sequential change of angiography for four months. A 54-year-old female, who had been treated for systemic lupus erythematosus (SLE), developed HZO on left ophthalmic nerve area. Seven weeks after the onset of HZO, she complained of headache, mild right hemiparesis, and disturbance of consciousness. Computed tomography revealed subcortical hemorrhage at the left temporo-occipital lobe. Cerebral angiography showed vascular irregularities such as segmental narrowing and sausage-like dilation on proximal portion of the ipsilateral anterior, middle and posterior cerebral arteries. Same findings were seen on peripheral portions of the posterior cerebral artery on the same side. Moreover sequential angiograms showed appearance of an aneurysm in the left middle cerebral artery (M2 potion). Under the diagnosis of cerebral angiitis associated with HZO, she was treated with antiviral agents, antiplatelet drugs, steroid and stellate ganglion block. Those irregularities were found to diminish on the sequential angiograms, and the aneurysm disappeared four month later. PMID- 7999443 TI - [A case of dissecting aneurysm associated with mixed connective tissue disease]. AB - A 41 year-old-female with mixed connective tissue disease (MCTD) associated with dissecting aneurysm (DA) of the right posterior cerebral artery is reported. This case satisfied the diagnostic criteria for MCTD, and cerebral angiography revealed the double-lumen sign and pooling of the contrast medium. Thus it was possible to make a definite diagnosis of both MCTD and DA. Fragility of the arterial wall due to the primary disease, MCTD, appeared to have played a role in the occurrence of dissection and the subarachnoid hemorrhage. PMID- 7999444 TI - [Clinical study of neuroleptic malignant syndrome in demented patients- examination of our case and reported cases]. AB - Recently, some cases of neuroleptic malignant syndrome (NMS) in demented patients have been reported, because the demented patients, who were administered neuroleptics due to their abnormal behaviors, have increased. We also experienced an 85-year-old male demented patient with NMS. His NMS was induced by haloperidol and disappeared by quitting the neuroleptic and a water supply. The post-NMS relapse of his abnormal behavior was ameliorated by a kind of herbal medicine "Ohren-Gedoku-Toh". We attempted to grasp the clinical characteristics of NMS in dementia by investigating the present case and reported cases. As the result, the following characteristics are suggested, (1) the NMS in dementia was seen more in vascular dementias than in Alzheimer's diseases, (2) in all the cases, the drug to be responsible to NMS was haloperidol, (3) a walking difficulty appeared at even the pre-stage or early stage of NMS, (4) the administration of dantrolene and/or bromocriptine was necessary to treat the patients with a high temperature. Moreover, examining our case, Levenson's criteria for NMS which regards a high serum CPK may be clinically more useful in the diagnosis of the NMS in dementia, because an early diagnosis and treatment can be done according to the criteria. PMID- 7999445 TI - [Transcortical sensory aphasia following a left frontal lesion--case report]. AB - We report a patient with transcortical sensory aphasia (TCSA) following a left frontal lesion. The patient was a 63-year-old right handed Buddhist priest admitted to our hospital with a complaint of word-finding difficulty. Neurological examination failed to reveal any abnormal findings except aphasia. The patients spontaneous speech was fluent, not agrammatic, and free of phonemic paraphasia but he sometimes exhibited semantic paraphasia. His ability to repeat sentences was excellent, but he had severe difficulty in word-finding, auditory comprehension and writing. He read aloud correctly, but his reading comprehension of kana (phonograms) was poor in contrast to excellent reading comprehension of kanji (morphonograms). His clinical picture was characterized by poor comprehension but excellent repetition, and a diagnosis of TCSA was made. CT and MRI revealed an infarction involving the pars opercularis and pars triangularis in the inferior frontal gyrus and the anterior portion of the lower prefrontal gyrus and the middle frontal gyrus. Regional cerebral blood flow was measured by single photon emission CT and was found to be decreased in the same region as indicated on CT and MRI. The clinical picture in this patient was comparable to that of TCSA due to a posterior parieto-occipital lesion, but the rapid improvement (within 1 to 2 months) of this patient was characteristic. Auditory comprehension, kana (phonograms) reading comprehension, and word recall, which were severely impaired in this patient, all demand interaction between phonological processes and semantic processes. Thus we conclude that this patient had impairment of the phonological-semantic interaction process. PMID- 7999447 TI - [Hemodynamic TIA associated with severe anemia--a case report]. AB - A 62-year-old man developed recurrent TIAs presenting as mild unconsciousness, dysarthria and weakness of the right upper extremity lasting for 15 to 20 minutes. He was found to have severe iron deficiency anemia (hemoglobin: 5.5 5.9g/dl; hematocrit: 18.4-19.5%) which insidiously developed through the chronic bleeding from the gastric ulcer. He had slight hypertension (184/86mmHg), but no orthostatic hypotension. DSA and MR angiography showed severe stenosis at the origin of the bilateral internal carotid arteries and of the left vertebral artery. There was also hypoplasia of the right vertebral artery. Blood circulation detected by 123I-IMP-SPECT was markedly decreased in the whole brain and in the right hemisphere of the cerebellum. TIA was, however, completely disappeared following to the recovery of anemia. The present case suggested that the presence of severe anemia accelerated the occurrence of hemodynamic TIA (regional cerebral anemic hypoxia), which is probably the consequence of the reduced oxygen-transporting capacity of the blood. PMID- 7999446 TI - [Characteristic event-related potentials evoked by somatosensory tasks in a patient with right-left disorientation and finger agnosia]. AB - Event-related brain potentials associated with both somatosensory and auditory detection tasks were recorded from the scalp in a 63-year-old man with finger agnosia and right-left disorientation resulted from cerebral infarction located around the region of the left angular gyrus. In a somatosensory oddball paradigm for discrimination between the right index finger (target, P = 0.2) and the left index finger (non-target, P = 0.8), early cognitive components P100, N140 and processing negativity were observed both in the target responses and non-target responses, however, no P300 component was recorded in both paradigms. In another paradigm to discriminate the index finger (target, P = 0.2) from small finger (non-target, P = 0.8) in the right hand, no P300 was evoked and only processing negativity was recorded both in the target responses and nontarget responses. These phenomena were obtained through characteristic behavior that the patient paid attention to the target stimuli as well as non-target stimuli and mentally counted them without discrimination. In contrast, in an auditory oddball paradigm P300 was clearly demonstrated to target stimuli that the patient correctly could count. The normal appearance of P300 in auditory detection tasks strongly suggests that the neural generator for the P300 was reserved intact. These results indicate that somatosensory information processing might be disturbed at the level of sensory discrimination needed for generation of P300 in our patient. It is also proposed that the neural events for somatosensory discrimination and auditory discrimination would take separate channels each other to reach the common generator of p300 in information processing. PMID- 7999448 TI - [Multiple meningioma associated with intraosseous and tentorial meningioma--case report]. AB - We report a case of multiple meningioma associated with intraosseous and tentorial meningioma. A 75-year-old woman was admitted to our hospital with blurred vision and exophthalmos in the left eye. Left lower hemianopsia, deterioration of visual acuity and right cerebellar signs were found on neurological examination. CT and MR image revealed an intraosseous tumor of the left sphenoid bone and a right tentorial mass. Cytogenetic analysis failed to reveal any abnormalities of chromosome 22. The intraosseous tumor which was transitional type meningioma and the tentorial mass, which was a fibroblastic meningioma were successfully excised. Postoperatively, the patient's symptoms and signs improved. Intraosseous meningioma associated with multiple meningioma is extremely rare and the histogenesis of meningioma arising from ectopic arachnoid cells is discussed. PMID- 7999449 TI - [A case of Klippel-Trenaunay-Weber syndrome associated with intracranial multiple angiomas]. AB - A case of Klippel-Trenaunay-Weber syndrome associated with multiple intracranial angiomas was reported. Intracranial angiomas with Klippel-Trenaunay-Weber syndrome is very rare. Only 4 cases are known to this day. A 24-year-old man fell at his workplace and suffered a head injury. He was admitted to our hospital. Neurological examination revealed no abnormality. However, physiological examination demonstrated hyperplasia and cutaneous hemangiomas of left lower leg, malformation of the left eyelid and clouding of the left cornea. CT showed left hemispheric atrophy and subdural effusion. MRI demonstrated multiple flow voids at the left cerebellar hemisphere and at pons. Cerebral angiogram demonstrated left cerebellar AVM and pontine angioma. Feeding arteries of the AVM were left superior cerebellar artery and left posterior inferior cerebellar artery. Those of the pontine angioma could not be identified. No spinal angiomas were revealed. While spinal angiomas associated with this syndrome are known, association of intracranial lesions are rare. Reported anomalies are angiomas, hemi-hypertrophy of skull and brain, carotid occlusion, megadolicoanomaly of the basilar artery, meningioma and glioma. Our case report with cerebral angiomas is the first one in Japan. We postulate that anomaly of our case originated at the Streeter's 2nd-3rd stage or that multiple anomalies occurred. We emphasize that intracranial, spinal or visceral angiomas, which can be fatal if it bleeds, should be routinely examined in Klippel-Trenaunay-Weber syndrome. PMID- 7999450 TI - [A 54-year-old man with generalized muscle atrophy and oculomotor paresis]. AB - We report a 54-year-old man with progressive generalized muscle atrophy and ophthalmoparesis in the terminal stage. He was well until 44 years of age (1982) when he noted weakness in his right hand and muscle atrophy; in May of 1985, he noted weakness in his left hand and in both legs. His weakness had become progressively worse, and he became unable to walk in November of 1985. He noted dysarthria one month later, and dysphagia in March of 1986. His difficulty in swallowing had also become worse; he regurgitated foods into the trachea in September of that year, and he developed a low grade fever on the same day. He was admitted to our service on September 24, 1987. On physical examination, general findings were unremarkable, except for low grade fever (37.3 degrees C). On neurologic examination, he was alert and mentally sound. He had normal vision and visual fields; ocular movements were normal. He had moderate weakness in facial muscles, dysarthria, dysphagia, and atrophy in his tongue. He had marked generalized muscle atrophy with fasciculation. He was unable to stand or walk. His muscle strength was not more than 1/6 in any part. The lower extremities were spastic. Deep reflexes were exaggerated in both lower extremities but were normal in upper extremities. Sensation was intact. Laboratory examination was unremarkable, and so was the cranial CT scan. He was treated with nasogastric feeding. He was able to communicate smoothly using his eyes, but a restriction in the vertical gaze was noted in February of 1989. The range of ocular movement was better in the oculocephalic reflex compared with his spontaneous vertical eye movements. In April of 1990, his horizontal gaze also had become slow, and he was complicated by bronchial asthma. He was treated with 20 mg/day of prednisolone; after the institution of prednisolone, his horizontal eye movement showed much improvement. In the terminal stage, he was able to move his eyes only very slowly; vertical gaze was impossible. His subsequent course was complicated by respiratory tract infection and septicemia, and he expired on July 15, 1992. The patient was discussed in a neurological CPC, and the chief discussant arrived at the conclusion that this patient had amyotrophic lateral sclerosis with oculomotor paresis. Post-mortem examination revealed spongy change involving the posterior column and the posterior spinocerebellar tract, in addition to severe degenerative change in the upper and the lower motoneurons, which were consistent with amyotrophic lateral sclerosis.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 7999451 TI - Breast Cancer in Younger Women. Proceedings of a conference. Bethesda, Maryland, January 28, 1993. PMID- 7999452 TI - Late effects of adjuvant therapy for breast cancer. PMID- 7999453 TI - Breast cancer and pregnancy. AB - Breast cancer treatment during pregnancy involves a host of psychosocial, ethical, religious, and even legal considerations, as well as medical multidisciplinary decisions, since the effect of treatment on the fetus must be considered. For example, breast or chest wall radiotherapy should be avoided. The absorbed fetal dosage is at least 5 cGy early in pregnancy and increases to several hundred cGy late in pregnancy to the fetal part immediately below the diaphragm. In the second and third trimesters, chemotherapy is associated with intrauterine growth retardation and prematurity in about half of the babies; the risk of birth defects is a concern in the first several weeks. Typical anesthetic agents readily reach the fetus but are not known to be teratogenic. Although abortion will allow full and comprehensive treatment to the mother, it is not known whether the procedure itself is therapeutic. Early in pregnancy, abortion deserves strong consideration, since the effects of treatment on the fetus will not be a consideration. The poor prognosis of pregnancy-associated breast cancer in the past is probably attributable to a combination of initial delay of diagnosis and possibly to unfavorable biologic characteristics of the hormonal milieu of pregnancy. When pregnant patients are matched stage for stage with controls, survivals seem equivalent, although pregnant patients present with more advanced disease. PMID- 7999454 TI - Breast cancer in young women: effect of chemotherapy on ovarian function, fertility, and birth defects. AB - A comprehensive review of the literature was done to assess the effect of adjuvant chemotherapy for operable breast cancer on ovarian function, fertility, and birth defects. Data were limited. Cyclophosphamide, an alkylating agent, is the major cause of amenorrhea, which is due to primary ovarian failure. Ovarian dysfunction is related to age, dose, and duration of treatment. In women less than 35, pregnancy following adjuvant chemotherapy is possible. However, data are limited regarding the impact of subsequent pregnancy on the results of breast cancer. There appears to be no increased risk of teratogenesis in offspring exposed to chemotherapy after the first trimester of pregnancy. Prospective data on women who have subsequent pregnancies and on their offspring are very limited. Formation of a registry for long-term follow-up of young women detailing reproductive potential and follow-up of offspring is needed. PMID- 7999455 TI - Pregnancy after breast-conserving surgery and radiation therapy for breast cancer. AB - Since the incidence of breast cancer is increasing in young women and young women are more commonly delaying child-bearing, the issue of considering a pregnancy subsequent to the diagnosis and treatment of breast cancer is becoming more common. The impact of a subsequent pregnancy on disease progression and quality of life is, however, not well defined. We evaluated treatment outcome and quality of life among 23 breast cancer patients treated with conservative surgery and radiation among the 1624 patients treated at the Joint Center for Radiation Therapy between 1968 and 1985 who had subsequent pregnancies as compared with 23 patients without subsequent pregnancy matched by age and stage at diagnosis and time to pregnancy without recurrence. Quality of life was evaluated using two self-report measures, Ferrans and Powers Quality of Life Index and the Adaptation to Surviving Cancer Profile, and a measure of parenting stress (Parenting Stress Index). Results showed no differences in recurrence or distant metastasis between the matched groups. In addition, subjects with subsequent pregnancy perceived that family issues had the greatest impact on quality of life and were not at higher risk for parental stress due to breast cancer than the normal population. Both groups of young women perceived that they were able to adjust well after treatment. Study results are consistent with other clinical studies comparing patients with and without subsequent pregnancy who have failed to demonstrate a survival disadvantage.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7999457 TI - Estrogen-replacement therapy in younger women with breast cancer. AB - Approximately 25% of breast cancers occur in premenopausal women. In addition to local therapy, surgery or surgery plus irradiation, systemic chemotherapy administration has become the standard of care for all node-positive and many node-negative patients. Systemic adjuvant chemotherapy can result in ovarian dysfunction or failure. This renders many women prematurely estrogen deficient. The consequences of menopause, genitourinary atrophy, bone loss, and increased risk of cardiovascular disease, have not been routinely assessed in clinical trials. The risks of estrogen deficiency have not been assessed in comparison to improved disease-free and overall survival benefits of adjuvantly treated premenopausal breast cancer patients. Estrogen-replacement therapy in postmenopausal women has been shown to prevent osteoporosis and reduce fracture risk. The majority of studies also show a marked reduction in cardiovascular disease and mortality. Estrogen-replacement therapy has been considered a disease prevention strategy rather than a therapeutic intervention. The risks and benefits of estrogen-replacement therapy in women with primary breast cancer are unknown. It is unknown how the well-known benefits accrued from reduction in skeletal and cardiovascular morbidity/mortality compare with the potential risks of increased breast cancer morbidity/mortality. Carefully designed prospective clinical trials with well-defined objectives and endpoints are required to learn if more harm than good is done by the withholding of estrogen therapy in breast cancer patients. PMID- 7999456 TI - Sex steroids and breast cancer prevention. AB - Mitogenesis and mutagenesis are major driving forces in neoplastic development. Little is known about important breast mutagens, but much is known about breast mitogens. "Blocking" the effect of breast cell mitogens, by reducing the actual exposure of the breast to them, is an obvious strategy for breast cancer prevention. The ovarian hormones, estrogens and progesterone, are major effective (direct or indirect) breast cell mitogens. There is overwhelming epidemiologic evidence that breast cancer risk is closely related to exposure to estrogens and progestogens. A woman's exposure to endogenous ovarian estrogens and progesterone is drastically reduced by the use of combination-type oral contraceptives (COCs), but the exogenous synthetic estrogen and progestogen in the COC effectively replace the ovarian estrogen and progesterone, so that no decrease in breast cell exposure to these hormones is obtained. Doses of estrogen and progestogen in modern COCs are close to the minimum attainable, while still retaining both contraceptive efficacy and ovarian suppression (so that endogenous estrogen and progesterone do not add to the dose of estrogen and progestogen from the COC). Considerably lower effective breast cell exposure to estrogen and progestogen can, however, be achieved by using a gonadotropin-releasing hormone agonist to suppress ovarian function and compensating for the resulting hypoestrogenemia with low-dose hormone replacement. Such a contraceptive is predicted to reduce lifetime breast cancer risk by more than 50% if used for 10 years and by as much as 70% following 15 years of use. Contraception represents a unique opportunity to have a substantial beneficial impact on women's health; more than 10 million women use COCs daily in the United States.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7999458 TI - Risk factors for breast cancer in younger women. AB - Epidemiologic studies of breast cancer that have included younger, premenopausal women in their populations have found that factors that predict altered risk of breast cancer after menopause can have different or even reversed effects before menopause. We have reviewed the literature on risk factors for breast cancer and their associations with breast cancer in general, and compared the risks for younger women with those for women diagnosed at older ages. Race, parity, and large body size are factors that may have opposite effects on breast cancer risk in younger and older women. Other factors of particular significance in the etiology of early-onset breast cancer include a late age at first birth, never having lactated, oral contraceptive use at early ages or of long duration, a family history of breast cancer, and a history of proliferative benign breast disease. PMID- 7999459 TI - Randomized prospective trial of estrogen-replacement therapy in women with a history of breast cancer. AB - With the onset of menopause, women develop increased risk for heart disease, vasomotor instability, and osteoporosis, which is related to estrogen deficiency, and can be corrected with estrogen-replacement therapy (ERT). Menopausal women with a history of breast cancer are advised against estrogen therapy because of concerns that ERT may adversely affect the course of the disease. There have been no prospective studies that address the issue of risk versus benefit for ERT in women with a history of breast cancer. We have initiated a randomized, prospective clinical study to define the influence, if any, of ERT on the clinical course of breast cancer (measure of potential risk) and the efficacy of ERT in the treatment of metabolic bone derangements (measure of benefit). Changes in serum lipids, cardiovascular events, and indices of psychological well-being are compared but do not constitute statistical end points. Eligible women must have had stage I or stage II breast cancer and must have had no evidence of disease for at least 2 years since therapy if estrogen-receptor-negative disease or for at least 10 years if the estrogen-receptor status is unknown. They were randomized to receive ERT (Premarin at 0.625 mg, days 1-25) versus no intervention (study control). Parameters of benefit and risk will be measured to detect a 10% change in disease-free rate for up to 5 years, with interim analyses at 20, 30, and 36 months of patient accrual. This study will allow us to begin the development of safe and effective strategies for the management of estrogen deficiency in patients with breast cancer.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7999460 TI - Nonhormonal alternatives for the management of early menopause in younger women with breast cancer. AB - Current medical practice recommends the use of alternatives to estrogen replacement therapy for the treatment of menopausal sequelae in younger women with breast cancer, although this clinical recommendation is undergoing reappraisal. Until prospective randomized studies addressing hormone use in this population are available, estrogen use in breast cancer patients will remain controversial. Because estrogen-replacement therapy is not the standard of practice and there is limited information available on nonestrogen therapies, women with breast cancer who are menopausal may not be prescribed or counseled about nonestrogen options. The efficacy, safety, and extent of use of most nonestrogen treatment modalities (other hormonal preparations, nonhormonal drugs, homeopathic preparations, and non-drug treatments) are not well documented and, unlike estrogen, many are selective in their benefit and do not share estrogen's universal impact. The use of several nonestrogen approaches for the prevention and treatment of osteoporosis has been promising. Traditional recommendations to maintain skeletal integrity, such as weight-bearing exercise; a diet rich in calcium and limited in caffeine, alcohol, and protein; avoidance of smoking; and measures to minimize trauma have been expanded to include the use or investigation of drugs (either alone or in combination). These drugs include progestins, vitamin D metabolites, injectable and intranasal synthetic salmon calcitonin, bisphosphonates, sodium fluoride, parathyroid hormone, growth factors, tamoxifen, etc. Strict control of the known risk factors, such as smoking, dyslipidemia, and hypertension as well as exercise, weight control, and the use of tamoxifen, are employed for the prevention and treatment of cardiovascular complications.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7999461 TI - Younger women at increased risk for breast cancer: perceived risk, psychological well-being, and surveillance behavior. AB - The problem of breast cancer in younger women has received increased attention in recent years. As yet, however, little is known about the surveillance patterns and psychological characteristics of younger women who are at increased risk for this disease. This report presents a summary of preliminary data on risk perceptions, surveillance behaviors, and psychological well-being among women with a family history of breast cancer, with particular attention to younger women (under age 50). These data show that over three fourths of women aged 29 and younger hold the belief that they are likely to develop breast cancer; this finding was not significantly different in other age groups. Surprisingly, over one third of women aged 29 and younger had received mammograms; over one half of women aged 30-34 had mammograms; and over three fourths of women aged 35 and older had mammograms. As many as one half of women aged 35-39 had mammograms within the past year. Serious psychological morbidity was not noted in the samples; however, one third of women of all ages reported breast cancer worries that impair their daily functioning. Psychological distress was associated with nonadherence to mammography and with both infrequent and excessive breast self examination practice. These data provide the basis for recommendations for research on breast cancer risk counselling for younger women. PMID- 7999462 TI - Sexuality and body image in younger women with breast cancer. AB - Breast cancer has the potential to be most devastating to the sexual function and self-esteem of premenopausal women. Nevertheless, not one study has systematically compared the impact of breast cancer treatment on sexual issues across age groups. Research shows that younger women with breast cancer have more severe emotional distress than older cohorts. In a group of patients seeking sexual rehabilitation in a cancer center, younger couples were more distressed, but also had the best prognosis with treatment. In theory, loss of a breast or poor breast appearance would be more distressing to women whose youth gives them high expectations for physical beauty. Seeking new dating relationships after breast cancer treatment is a special stressor for single women. Potential infertility also may impact on a woman's self-concept as a sexual person. Systemic treatment disrupts sexual function by causing premature menopause, with estrogen loss leading to vaginal atrophy and androgen loss perhaps decreasing sexual desire and arousability. Research on mastectomy versus breast conservation across all ages of women has demonstrated that general psychological distress, marital satisfaction, and overall sexual frequency and function do not differ between the two treatment groups. Women with breast conservation do rate their body image more highly and are more comfortable with nudity and breast caressing. There is some evidence that breast conservation offers more psychological "protection" for younger women. Research on the impact of breast reconstruction is sparse, but reveals similar patterns. Future studies should use rigorous methodology and focus on the impact of premature menopause and the effectiveness of sexual rehabilitation for younger women. PMID- 7999463 TI - Breast cancer in younger women: effects on interpersonal and family relations. AB - Although breast cancer can have a stressful impact on women of all ages, young women may be particularly vulnerable to the negative effects of the disease. Based on a developmental perspective, this article reviews studies on the emotional impact of breast cancer on young women, their spouses, children, and the marital relationship. Studies indicate that younger women experience more emotional distress than older women, although the inverse relationship between age and emotional distress is not consistent across all studies. Although age does not appear to have a direct relationship to husbands' adjustments, younger husbands reported more problems carrying out domestic roles and a greater number of life stresses than older husbands. Studies on the impact of breast cancer on children are limited in number and scope but indicate that the effects of breast cancer vary according to the developmental level of the child. Directions for further research on young women and their families are suggested. PMID- 7999464 TI - Age differences in the psychosocial problems encountered by breast cancer patients. PMID- 7999465 TI - Risk and timing of counseling and support interventions for younger women with breast cancer. PMID- 7999466 TI - Pathology and heredity of breast cancer in younger women. AB - The pathology of early-age onset breast cancer is considered here from three perspectives: 1) benign proliferative disease, 2) the cancers themselves, and 3) familial and hereditary breast cancer. Hereditary breast cancer, a subset of familial breast cancer featuring a strong autosomal dominant pedigree pattern and multiple primary cancers, has a strong predilection for younger women, accounting for about one half of breast cancers under age 30. With respect to benign proliferative disease, the increased relative risk of breast cancer associated with proliferative disease with atypia, about fourfold to fivefold for all ages, is doubled by the presence of a family history of breast cancer and amplified by young age. With respect to the carcinomas, the relative incidences of medullary carcinoma and ductal carcinoma in situ are increased in young women, while lobular and tubular carcinomas are decreased. Invasive breast cancer is higher grade and more proliferative in younger women, as measured by thymidine-labeling index, DNA flow cytometric S-phase fraction, and proliferation-associated proteins. The increased fraction of ductal carcinoma in situ and higher grade invasive cancers may help to account, respectively, for increased recurrence rates with conservative therapy, and more aggressive natural history in younger women. Familial breast cancers show trends for increased medullary type, but the effect is not independent of age. Weak associations of family history with tubular carcinoma have been reported, but data for associations with lobular carcinoma in situ and invasive lobular carcinoma are conflicting. Hereditary breast cancer as a class has higher tumor proliferation rates, an effect independent of age. Knowledge of the pathology and biomarker characteristics of BRCA1 gene-linked hereditary breast cancers, which account for a substantial fraction of breast cancers in younger women, should shed light on the nature of the responsible gene(s) and guide approaches to therapy and prophylaxis. PMID- 7999467 TI - Breast cancer outcome and predictors of outcome: are there age differentials? AB - Several questions were addressed regarding breast cancer outcome, predictors of outcome, and young age at diagnosis. Is there evidence that outcome is worse in younger women compared with other age groups? Do younger patients have a greater frequency of adverse prognostic factors? If younger age is associated with a poor outcome, is it an intrinsic independent adverse predictor, or is the outcome worse due to poor prognostic factor profiles? Several methods were used to answer these questions and applied to those reports in which age categories were carefully defined: 1) detailed review of population-based breast cancer outcome literature, 2) synthesis of published cooperative group and single institution univariate and multivariate analyses, and 3) a new analysis of the 8738-patient San Antonio database. Overall, epidemiologic studies suggested that younger women have the worst survival outcome, when matched with similarly staged older cohorts. Univariate trends analyses confirmed that younger women more often had more positive lymph nodes, larger tumors, and negative steroid hormone receptors. Significantly more cancers in women less than 35 years of age had high S-phase fractions and abnormal expression of p53. Multivariate modeling confirmed that young age was an independent adverse predictor when a few standard factors were considered in the model, but other descriptors such as tumor grade or high S phase fraction were more important when available. These data support the conclusion that "young age" serves as a surrogate for a greater frequency of adverse prognostic factor profiles and suggest important questions for future study. PMID- 7999468 TI - Patterns of care for younger women with breast cancer. PMID- 7999470 TI - Screening younger women at risk for breast cancer. AB - In women older than 50 years, screening mammography offers the benefits of decreased mortality from breast cancer, increased use of conservative surgery, and the reassurance of being free of breast cancer after a negative examination. No similar data are available for younger women. The cost to avert a single death from breast cancer in younger women may be $2 million or more. One proposed strategy to improve the performance of screening mammography in younger women and to lower its cost is to restrict its use to women with risk factors for breast cancer, but this strategy will miss cases occurring in women who have no identifiable breast cancer risk factors. Because mammographic screening performance is different in younger women compared with older women, individual screening prescriptions based on risk may be appropriate until definitive trials demonstrate a mortality benefit in younger women. Additional research is needed to define the optimal screening strategy for both the entire population of women younger than 50 and those who are at increased risk for breast cancer. PMID- 7999469 TI - Genetic epidemiology of breast cancer in younger women. AB - Genetics plays a role in all of breast cancer. At present, however, inherited genes associated with the development of breast cancer have more frequently been identified in women with an early age at onset. This review examines the extent to which genetic information, at both an epidemiologic and molecular level, may be used to identify a subset of women who are likely to be at increased risk of developing breast cancer at an early age. PMID- 7999471 TI - Prevention of breast cancer in premenopausal women. AB - While all-inclusive complete models for breast cancer development are not available, four concepts are likely to be critical to creation of well-grounded breast cancer prevention efforts: 1) step-by-step progressive development, 2) involving multiple factors, 3) over several years, and 4) during a long period of which the process may be reversible. Interventions to prevent breast cancer must have a comprehensive biological rationale, an absence of serious toxic effects, and long-term acceptability by women. Prophylactic mastectomy may be beneficial in some women, but identification of individuals at very high risk for breast cancer remains elusive. At present, greater attention to four manipulable risk factors is appropriate: radiation, smoking, alcohol, and lactation. Clinical trials are in the process of studying a synthetic retinoid (4 hydroxyphenylretinamide), tamoxifen, and a low-fat diet. Other breast cancer prevention strategies in various phases of preclinical trial evaluation include: pseudopregnancy, an "ideal" combination oral contraceptive, luteinizing hormone releasing hormone (LHRH) agonist oophorectomy, modification of estrogen metabolism, suppression of ornithine decarboxylase induction, and manipulation of growth factors. PMID- 7999472 TI - Survival patterns among younger women with breast cancer: the effects of age, race, stage, and treatment. AB - Several hundred studies of breast cancer survival are published each year; yet few of them include women under the age of 50, and almost none of them specifically examine prognosis among women in their 20s through 40s. The few published reports that analyze survival after breast cancer among these young patients do not provide a consistent or definitive description of their survival experience. The National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) Program offers a unique opportunity to analyze breast cancer survival in depth among younger women. In this report, survival patterns of all black and white women diagnosed with breast cancer between 1983 and 1989, aged 20 and older, microscopically confirmed, and undergoing surgery, in the SEER program have been analyzed. There are 77,368 women included in this study, 92.8% of whom were white. Less than 1% (562 patients) of these breast cancer patients were between the ages of 20 and 29, 6.5% (5062 patients) were 30-39, and 15.2% (11,789 patients) were 40-49. Survival was calculated utilizing a mixture model to evaluate the cause-specific hazards of dying of breast cancer versus dying of other causes of death. We investigated the hazard of dying of breast cancer versus other causes of death by age at diagnosis, year of diagnosis, extent of disease and diagnosis, and treatment. Stage was stratified into three categories: 1) cases with no axillary lymph node involvement, 2) cases with axillary lymph node involvement, and 3) cases with distant metastases.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7999473 TI - Trends in breast cancer in younger women in contrast to older women. AB - Using data from the Surveillance, Epidemiology, and End Results (SEER) Program and the National Center for Health Statistics, trends in female breast cancer rates were examined for the time period 1973-1989 for the age group 20-39 and contrasted with those for older ages. Only about 7% of breast cancers occur by the age of 40; the risk of developing breast cancer prior to the age of 40 is less than 1%. The incidence trends for women in the 20-39 age group have been essentially stable, whereas for women 40 and older the rates increased steeply during the 1980s (at a faster rate than anticipated based on historical trends) and then leveled off beginning in 1987. Breast cancer mortality has been much more stable over time than incidence. Up to age 40, blacks have a higher incidence than whites. Over age 40, white rates exceed those for blacks, and the absolute and relative differences in incidence increase with advancing age. For whites, 5-year relative survival rates improved with advancing age up to age 50. Blacks under the age of 30 had survival rates similar to whites, whereas, in the older age groups, whites had somewhat better survival rates overall and by stage. The occurrence of second cancers was also analyzed in women with a first invasive breast cancer. Cancers found to occur at higher than expected rates included leukemia and cancers of the breast, ovary, and lung. PMID- 7999474 TI - Breast cancer in young women: issues in local therapy. AB - Although age has been studied as a prognostic factor in breast cancer, little attention has been paid to its role in the selection and outcome of local therapy. A review of 42 breast cancer patients less than 40 years of age treated at the University of Chicago from 1989 to 1992 demonstrated that of women with stage 0, I, or II disease, 37% had medical contraindications to breast preservation compared with 25% of women over 40. Twenty-one percent of young women eligible for conservation opted for mastectomy and reconstruction compared with 9% of their older counterparts. Only 4% of women in either age group selected mastectomy alone as therapy. The literature on the relationship of age to local failure after breast conservation and the long-term morbidity of the local therapy of breast cancer is reviewed. Further research to clarify issues in local therapy in young patients is proposed. PMID- 7999475 TI - Menstrual timing of treatment for breast cancer. AB - Although the hormone dependency of breast cancer has been recognized for nearly a century, the influence on disease progression of cyclical hormonal levels among premenopausal women has not been extensively researched. The findings of recent studies, assessing the effect on prognosis of the hormonal milieu at the time of surgery, have been conflicting. However, several reports have noted improved survival among patients with positive, axillary lymph nodes surgically treated in the later phase of the menstrual cycle when progesterone levels are elevated. Biologic support for the influence of menstrual timing is provided by cyclical patterns of cell division and cell death observed in normal breast tissue as well as potential tumor cell dissemination during surgery among patients with positive axillary nodes. Immune parameters, which also respond to cycling endogenous hormones, may influence the metastatic potential of circulating tumor cells. Comparisons among studies of menstrual timing of surgery have been complicated by differences in cycle divisions, extent of primary surgery, frequency of adjuvant therapy, duration of follow-up, and analytic procedures. Although several clinicians are now scheduling breast surgery of premenopausal women in relation to day of the menstrual cycle, a majority of surgeons have deferred consideration of menstrual timing until additional research is available. While waiting 5-10 years for the results of prospective studies, additional retrospective analyses, using carefully collected data, may provide clinical guidance. With increasing concern for issues related to women's health, multidisciplinary studies will be required to adequately characterize the influence of the menstrual cycle and other aspects of women's reproductive physiology on breast cancer and other medical conditions. PMID- 7999476 TI - Study of access recirculation in reversed temporary indwelling catheters. AB - At the Ottawa Civic Hospital hemodialysis unit, our prescribed blood flow rate for temporary indwelling catheters runs at 200 mls/min. We were concerned that, with the reversal of the ports of these catheters, our patients were not receiving the dialysis prescription ordered for them due to decreased efficiency of their treatment. Twenty-five of 108 patients in the program were included in a study related to the percentage of access recirculation when ports were reversed or not reversed. Of those 25 patients, approximately 42% had their ports reversed. The study took place over a two-week period and involved approximately six dialysis sessions per patient. Results indicated that the percentage recirculation increased from 2.3%-4.1% when ports were connected normally, to 12% when ports were reversed. As a result, a policy is now in place whereby our patients' treatment time is increased 20 minutes for reversed ports. In summary, recirculation rate increased with reversal of ports in temporary indwelling catheters. Extension of prescribed treatment times when ports are reversed will maintain the efficiency of dialysis. PMID- 7999477 TI - [The liaison nurse in pediatric renal transplantation, at the heart of communication]. PMID- 7999478 TI - Canadian Organ Replacement Register. PMID- 7999479 TI - Peripheral nerve damage and regional anaesthesia. PMID- 7999480 TI - Post-circumcision analgesia: comparison of topical analgesia with dorsal nerve block using the midline and lateral approaches. AB - Forty-five patients undergoing circumcision were allocated randomly to one of three study groups to compare topical analgesia with dorsal nerve block using the midline or lateral approach. Pain scores, side effects and analgesic requirements were recorded after surgery. Patients who received topical analgesia required significantly more fentanyl and had higher pain scores at the 15-min observation period after operation. Fentanyl requirements and pain scores were similar in patients who received a dorsal nerve block using either the midline or lateral approach. The incidence of side effects after surgery was similar in all three groups. PMID- 7999481 TI - Pre-emptive analgesia: comparison of preoperative with postoperative caudal block on postoperative pain in children. AB - We have compared in 25 children the effect of preoperative with postoperative caudal block on pain after circumcision in a double-blind, randomized study. After induction of anaesthesia, patients were allocated randomly to receive a caudal block either before (n = 14) or immediately after (n = 11) surgery. Postoperative pain was rated on a paediatric pain scale. If pain occurred, children received paracetamol in a dose related to body weight. Using the Mann Whitney U test (significance < or = 0.05) there was no significant difference in cumulative postoperative analgesic requirements within the first 48 h and in times to first analgesic administration between the groups. Cumulative pain score, assessed every 30 min for the first 8 h after operation, was significantly lower for those patients who received caudal anaesthesia after operation. Thus we could not demonstrate any advantage in performing caudal block before compared with after surgery. PMID- 7999482 TI - Intraoperative glycaemic control in non-insulin-dependent and insulin-dependent diabetes. AB - We have compared intraoperative glycaemic control, insulin requirements and metabolic and endocrine variables in 40 non-insulin-dependent diabetic patients (NIDDM) and 40 insulin-dependent diabetic patients (IDDM) undergoing general anaesthesia for elective procedures. Two i.v. insulin regimens were used: continuous i.v. infusion (group A: 1.25 u.h-1) and repeated i.v. boluses (10 u./2 h). Blood concentrations of glucose were measured every 15 min from just before induction of anaesthesia until 2 h after surgery. Plasma lactate and pyruvate concentrations, ketone bodies, C-peptide and counter-regulatory hormones were also measured. Glycaemia did not differ significantly in the two types of diabetes, regardless of the insulin therapy used. The amounts of insulin administered were similar in NIDDM and IDDM. There was no significant difference for other metabolic variables. Plasma concentrations of growth hormone (GH) increased significantly during surgery, especially in IDDM patients, but this change did not alter intraoperative glycaemic control. We conclude that mean glycaemic control, insulin requirements and development of ketone bodies in NIDDM and IDDM patients did not differ during the operative period, regardless of the insulin regimen used. Therefore, during the operative period, it is not necessary to modify the insulin regimen according to the type of diabetes. The consequences of increased plasma GH concentrations on glycaemic control in IDDM patients after operation are unknown. PMID- 7999483 TI - Effects of passive and active smoking on induction of anaesthesia. AB - It is said that cigarette smokers suffer stormy induction of anaesthesia; although plausible, this is unsubstantiated. We have studied the incidence of adverse events during induction, together with peripheral oxygen saturation (SpO2), in active and passive smokers, and in non-smokers. During induction, both active and passive smokers had a higher incidence of adverse events than non smokers (P < 0.01 and P < 0.05, respectively). Irrespective of smoking status, those suffering adverse events had greater concentrations of carboxyhaemoglobin and suffered more oxygen desaturation than those not suffering such events. Although we were unable to demonstrate a direct link between smoking status and oxygen desaturation during induction, our study gives a firmer basis for exhorting patients not only to stop smoking before anaesthesia but also to avoid passive smoking. PMID- 7999484 TI - Efficiency of the Carden "Ventmasta" in A and D modes during controlled ventilation in children. AB - We have determined the efficiencies of the enclosed Mapleson A and Mapleson D modes of the Carden "Ventmasta" ventilator during controlled ventilation in 19 anaesthetized children. In addition, we determined the suitability for the A mode of the fresh gas formula, VF = 0.6 x weight0.5. Efficiency was assessed in terms of the fraction of fresh gas delivered to the alveoli. When the minute volume to fresh gas flow ratio exceeded 1.5, fractional delivery of fresh gas was 23% greater in the A mode than in the D mode (0.74 vs 0.60) (P < 0.0001). Under the same conditions, mean end-tidal carbon dioxide concentration in 27 children undergoing ventilation in the A mode with VF = 0.6 x weight0.5 was 4.6% (range 3.5-5.4%). We conclude that the Carden system is up to 23% more efficient in the A mode than in the D mode, and that under the conditions of this study, normocapnia or mild hypocapnia was produced accurately using the formula VF = 0.6 x weight0.5. PMID- 7999485 TI - Effect of ventilation on first-pass pulmonary retention of alfentanil and sufentanil in patients undergoing coronary artery surgery. AB - We have studied, in 14 patients undergoing elective aorto-coronary bypass surgery, the effect of the type of ventilation on pulmonary retention of alfentanil and sufentanil using a double indicator technique. Patients were allocated to one of two groups to receive either bolus doses of sufentanil 33.2 micrograms (n = 6) or alfentanil 654 micrograms (n = 8), mixed with indocyanine green. In each patient, pulmonary first-pass retention was studied during apnoea (during the 1-min study period), normoventilation and positive end-expiratory pressure (10 mm Hg) ventilation, the order of which was randomized. After sufentanil, mean (95% confidence interval) first-pass pulmonary retention was 50.9 (41.7-60.1)% during apnoea, 50.8 (42.9-58.8)% during normoventilation and 54.4 (43.7-65.0)% during positive end-expiratory pressure ventilation. After alfentanil, first-pass pulmonary retention was 18.7 (5.4-32.0)% during apnoea, 19.9 (8.3-31.5)% during normoventilation and 16.6 (5.6-27.6)% during positive end expiratory pressure ventilation. First-pass pulmonary retention of alfentanil and sufentanil was not significantly affected by the type of ventilation. PMID- 7999487 TI - Effects of oral ranitidine, famotidine and omeprazole on gastric volume and pH at induction and recovery from general anaesthesia. AB - We have studied, in 150 patients undergoing elective general surgery, the effect on gastric content of omeprazole 40 mg, ranitidine 300 mg and famotidine 40 mg, given orally the night and the morning before surgery. Volume and pH of gastric content were measured at induction and recovery from anaesthesia. Gastric volumes did not differ between groups. The median gastric pH was lower with omeprazole compared with ranitidine and famotidine at intubation (5.11, 7.05 and 6.99, respectively) (P < 0.001) and extubation (6.41, 6.98 and 6.96) (P < 0.001). The proportion of patients with gastric pH < 2.5 at induction was 40% for omeprazole, 12% for famotidine and 10% for ranitidine (P < 0.02); the proportion did not differ significantly at extubation. PMID- 7999486 TI - Spinal anaesthesia for caesarean section: comparison of infusions of phenylephrine and ephedrine. AB - Maternal cardiovascular changes and neonatal acid-base status were assessed in 29 healthy women undergoing elective lower segment Caesarean section under spinal anaesthesia. The patients were allocated randomly to one of three groups to receive an i.v. infusion of one of the following: ephedrine 1 mg min-1 (group E1: n = 10), ephedrine 2 mg min-1 (group E2: n = 9), or phenylephrine 10 micrograms min-1 (group P: n = 10). Invasive arterial pressure was monitored continuously and if hypotension occurred (defined as a 20% decrease from baseline, taken after i.v. preload administration), bolus doses of either ephedrine (6 mg in groups E1 and E2) or phenylephrine (20 micrograms in group P) were given. Only four patients became hypotensive in group E2, compared with eight patients in group E1 and nine patients in group P. The total time that the patients remained hypotensive was greatest in group P (P < 0.005), less in group E1 and least in group E2. Neonatal Apgar scores and acid-base profiles were similar in all three groups. In this study, an infusion of phenylephrine 10 micrograms min-1 with bolus doses of 20 micrograms was shown to be significantly less effective in maintaining systolic arterial pressure within 20% limits of baseline compared with an infusion of ephedrine 1 or 2 mg min-1 with bolus doses of 6 mg. PMID- 7999488 TI - Effects of midazolam and diazepam as premedication on heart rate variability in surgical patients. AB - We have examined the effects of midazolam 0.06 mg kg-1 i.m. and diazepam 0.2 mg kg-1 orally as premedication on the spectral components of heart rate (HR) variability in 24 elderly patients aged 65-87 yr and 24 young patients aged 18-35 yr undergoing elective surgery. The low-frequency/high-frequency (LF/HF) ratio of HR variability increased after arrival in the operating room in elderly patients who received no premedication, but not in young patients. In elderly patients who received midazolam or diazepam, the LF/HF ratio did not increase. However, diazepam increased the low-frequency component and the total power of HR variability in both young and elderly patients. We conclude that cardiac sympathetic nerve activity increased after arrival in the operating room in the elderly, that midazolam or diazepam reduced this increase and that diazepam caused an increase in the total power of HR variability that has not been observed for other agents. PMID- 7999490 TI - Mivacurium in the myasthenic patient. AB - We have used mivacurium in four myasthenic patients presenting for thymectomy. Supramaximal single twitch stimulation was applied to the ulnar nerve at the wrist and the force of contraction of the adductor pollicis was measured. After an initial bolus dose of 30 micrograms kg-1 (approximately one-fifth of the normal intubating dose), we observed a mean 37.5 (SEM 5.6)% reduction in evoked twitch tension. Neuromuscular block was increased with incremental doses and maintained with repeat bolus doses of 15 micrograms kg-1 at 25% recovery. The interval between maintenance bolus doses remained constant (mean 5.9 (0.7) min). Spontaneous offset was rapid with a mean recovery index (T25-T75) of 11.9 (2.1) min. Provided anticholinesterase therapy is withheld in the immediate preoperative period, mivacurium would appear to be a safe and appropriate neuromuscular blocker in this variably sensitive group of patients. The cumulative dose required to establish full neuromuscular block varied between 60 and 90 micrograms kg-1. A maintenance infusion, commencing at 3 micrograms kg-1 min-1, is recommended, guided by neuromuscular monitoring. PMID- 7999489 TI - Interactions between mivacurium and atracurium. AB - We have studied the interaction between atracurium and mivacurium. The dose response relationships of atracurium, mivacurium and their combination were studied in 96 ASA I or II patients during thiopentone-fentanyl-nitrous oxide isoflurane (1.2% end-tidal) anaesthesia. Neuromuscular block was recorded as the evoked thenar mechanomyographic response to train-of-four stimulation of the ulnar nerve (2 Hz at 12-s intervals). The dose-response curves were determined by probit analysis. Isobolographic and algebraic (fractional) analyses were used to assess quantitatively the combined effect of equipotent doses of atracurium and mivacurium and to define the type of interaction between these drugs. Isobolograms were constructed by plotting single drug ED50 points on the dose co ordinates and a combined ED50 point in the dose field. The calculated doses producing 50% depression (ED50) of the first twitch height were 50.5 (95% confidence intervals 48.9-52.1) and 20.8 (20.3-21.3) micrograms kg-1 for the atracurium and mivacurium groups, respectively. Isobolographic and fractional analyses of the atracurium-mivacurium combination demonstrated zero interaction (additivism). An additional 26 patients anaesthetized with thiopentone-fentanyl nitrous oxide-isoflurane were allocated randomly to receive either atracurium 0.5 mg kg-1 (n = 13) or mivacurium 0.15 mg kg-1 (n = 13). Additional maintenance doses of mivacurium 0.1 mg kg-1 were administered to patients in both groups, whenever the first twitch recovered to 10% of control. The duration of the first maintenance dose of mivacurium to 10% recovery of the first twitch was greater (P < 0.0005) after atracurium (25 (21.8-28.5) min) than after mivacurium (14.2 (11.9 16.6) min).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7999491 TI - Inhaled nitric oxide in acute respiratory failure in adults. AB - We have assessed the acute effects of inhaled nitric oxide 8, 32 and 128 volumes per million (vpm) on pulmonary haemodynamics and arterial oxygenation in patients with severe acute respiratory failure. Fourteen patients requiring artificial ventilation with mean pulmonary artery pressures greater than 30 mm Hg were given inhaled nitric oxide; haemodynamic values and blood-gas tensions were measured before and after 10 min of inhalation of nitric oxide. Nitric oxide inhaled at 8, 32 and 128 vpm decreased mean pulmonary artery pressure by 1.7 (SD 2.2), 3.2 (2.6) and 3.3 (3.3) mm Hg, pulmonary vascular resistance by 20 (64), 53 (57) and 66 (54) dyn s cm-5 and increased arterial oxygen tension by 2.5 (3.6), 3.0 (5.1) and 2.9 (3.9) kPa, respectively. All changes were significant (P < 0.05 or less) except for changes in pulmonary vascular resistance at 8 vpm. The improvement in arterial oxygenation with 128 vpm was related to pulmonary vascular resistance before commencing nitric oxide. The major beneficial effect of nitric oxide in acute respiratory failure would appear to be improvement in oxygenation rather than reduction in pulmonary artery pressure. The degree of improvement in arterial oxygenation with nitric oxide was related directly to pulmonary vascular resistance before treatment. PMID- 7999493 TI - Effect of halothane on cilia beat frequency of ciliated human respiratory epithelium in vitro. AB - The effect of halothane on human ciliated nasal epithelium was studied in vitro. Samples from 24 healthy adult volunteers were exposed to halothane in varying concentrations and cilia beat frequency was measured using the transmitted light technique. Mean cilia beat frequency was measured at 30-min intervals. There was a significant decrease in cilia beat frequency at 2 h in samples that were exposed to halothane (mean 8.4 (SD 2.5) Hz, 9.18 (2.6) Hz and 6.99 (4.9) Hz) compared with air (10.8 (2.7) Hz, 11.6 (2.1) Hz and 12.1 (2.3) Hz) (P < 0.01). The coefficient of variation of cilia beat frequency measurements increased after exposure to halothane. There was no change in the cilia beat frequency of controls exposed to air over a 3-h period. PMID- 7999492 TI - Near-infrared spectroscopy in adults: effects of extracranial ischaemia and intracranial hypoxia on estimation of cerebral oxygenation. AB - We have studied the effects of extracranial ischaemia and intracranial hypoxia on measurement of cerebral oxygenation using near-infrared, reflectance-mode, cerebral oximetry (Invos 3100 cerebral oximeter) in healthy adult subjects. Under stable systemic conditions, scalp ischaemia induced by a pneumatic tourniquet caused an apparent reduction in mean regional cerebral oxygenation (rSO2) from mean 72 (SD 6)% to 59 (7)% (n = 8, P < 0.001). rSO2 returned to control values within 1 min of release of the tourniquet. Local scalp ischaemia induced by rapid frontalis muscle exercise caused a significant reduction (4.5 (2)% in rSO2 (n = 12, P < 0.001). The effect of systemic hypoxia on rSO2 was examined during controlled scalp ischaemia. A decrease in mean SpO2 from 98 (2)% to 66 (6)% was associated with a decrease in mean rSO2 from 57 (4)% to 41 (6)%. There was a significant correlation between the percentage reduction in rSO2 and SpO2 during hypoxia (r = 0.81, P < 0.001). We conclude that the Invos cerebral oximeter was capable of detecting tissue hypoxia deep to the scalp under carefully controlled conditions but that it also was affected significantly by changes in extracranial blood flow and oxygenation which may affect its reliability in clinical practice. Further work is necessary to define those situations in which cerebral oximetric monitoring is useful and valid. PMID- 7999494 TI - Effect of methylene blue on the vasodilator action of inhaled nitric oxide in hypoxic sheep. AB - We have examined the effect of methylene blue 4mg kg-1 on the pulmonary vasodilator action of inhaled nitric oxide (8, 32, 128 and 512 volumes per million) in nine sheep with pulmonary hypertension induced by hypoxia (FlO2 = 0.12). The dose-response to nitric oxide was unchanged by methylene blue, but increased cardiac output was noted (P < 0.01). These results indicate that methylene blue may not inhibit the action of nitric oxide on guanylate cyclase, as suggested previously, and that treatment of methaemoglobinaemia occurring during therapeutic inhalation of nitric oxide with methylene blue may not block the vasodilator effect of nitric oxide on the pulmonary vasculature. PMID- 7999495 TI - Comparison of clonidine with fentanyl on phrenic nerve activity and their interaction in anaesthetized rabbits. AB - We have compared the effects of clonidine and fentanyl on phrenic nerve activity in anaesthetized rabbits during artificial ventilation. Both drugs caused dose dependent inhibition of phrenic nerve activity and complete abolition in all experiments. The calculated ED50 values were 3.7 micrograms kg-1 for clonidine and 3.9 micrograms kg-1 for fentanyl. Pretreatment with clonidine 1 microgram kg 1 i.v. depressed phrenic nerve activity to 81.8% of control values. This effect was additive with subsequent doses of fentanyl which was confirmed with an ED50 isobologram. We conclude that clonidine has the potential for deleterious respiratory effects at doses similar to those of fentanyl, but the interaction between the two drugs is additive and hence differs from their known synergistic antinociceptive interaction. PMID- 7999496 TI - Autoradiographic determination of regional cerebral blood flow and metabolism in conscious rats after fluid resuscitation from haemorrhage with a haemoglobin based oxygen carrier. AB - The effects of resuscitation fluids on the brain have been investigated in previous studies by global measurements of cerebral blood flow and metabolism. In this study we have examined the effects of a novel haemoglobin-based oxygen carrier on local cerebral blood flow (LCBF) and local cerebral glucose utilization (LCGU) after resuscitation from a volume-controlled haemorrhage of 30 min (3.0 ml/100 g body weight) with ultrapurified, polymerized, bovine haemoglobin (UPBHB). LCBF and LCGU were measured in 34 brain structures of conscious rats 2 h after resuscitation using quantitative iodo(14C)antipyrine and 2-(14C)-deoxy-D-glucose methods. The data were compared with a control group without haemorrhage and fluid resuscitation. In the haemorrhage group, LCBF increased after resuscitation by 12-56% in the different brain structures (mean 36%). LCGU changed less (0 to +18%, mean +9%). In the control group there was a close relationship between LCGU and LCBF (r = 0.95). After fluid resuscitation the relationship was preserved (r = 0.95), although it was reset at a higher ratio of LCBF to LCGU (P < 0.05). We conclude that fluid resuscitation of a 30 min volume-controlled haemorrhage using the haemoglobin-based oxygen carrier, UPBHB, induced a moderate degree of heterogeneity in the resulting changes of LCGU and LCBF. Local disturbances of cerebral blood flow or metabolism were not observed. PMID- 7999497 TI - Preoperative fasting for paediatric anaesthesia. AB - Preoperative fasting was introduced to reduce the risk and severity of aspiration pneumonitis. Adequate time (6h) must still be allowed before operation for solid foods to be emptied from the stomach. However, the overwhelming weight of evidence supports the practice of reducing the duration of the preoperative fluid fast for elective paediatric surgical patients [3, 15]. In children allowed free, clear fluids until 2 h before the scheduled time of anaesthesia, gastric contents and thus the risk of aspiration pneumonitis appears to be similar to those children who have endured a longer fast. Potential benefits of reduced thirst, better perioperative experience, improved compliance and reduced hypoglycaemia may be seen. Patients at risk of GOR and aspiration pneumonitis, including those presenting for emergency surgery, must receive special consideration. As aspiration pneumonitis is so rare, careful reporting of complications potentially related to a reduced fasting period is necessary. PMID- 7999498 TI - Myocardial ischaemia during tracheal intubation and extubation. AB - The incidence of myocardial ischaemia during tracheal intubation and extubation was compared using ambulatory ECG monitoring in 60 patients undergoing a variety of different surgical operations. Seven patients had myocardial ischaemia after tracheal intubation and seven patients during tracheal extubation. The patients who developed myocardial ischaemia during tracheal extubation had significantly greater rate-pressure products immediately before tracheal extubation (P < 0.05) and 1 min after tracheal extubation (P < 0.01) compared with those patients who did not develop myocardial ischaemia during extubation. PMID- 7999499 TI - Posterior column sensory impairment during ambulatory extradural analgesia in labour. AB - Ambulatory or "walking" extradural analgesia in labour has recently gained popularity because of preservation of motor function and subjective somatic sensation in the lower limbs, resulting in increased maternal satisfaction. This is produced by combining dilute concentrations (e.g. 0.1%) of bupivacaine with opioids. Detailed clinical neurological examination after mobile extradural analgesia has not been reported. We have investigated the effect of 0.1% bupivacaine 15 ml and fentanyl 2 micrograms ml-1 on motor and sensory function in the lower limbs in 50 primigravidae requesting extradural analgesia in labour. This was performed before and 30 min after confirming placement of a lumbar extradural catheter. While power, co-ordination and reflexes in all lower limb muscle groups remained within normal limits, 66% (n = 33) developed abnormal distal proprioception, 44% (n = 22) had a positive Romberg's sign and 38% (n = 19) had altered vibration sense. Moreover, 44% (n = 22) said that their legs felt different on standing and they did not feel confident walking unaccompanied. However, this subjective perception correlated poorly with the presence of posterior column sensory signs. Although there was a reduction in pain scores on a visual analogue scale after 30 min (mean 8.85 (SEM 0.3) vs 3.06 (0.32); P < 0.0001), pain increased within 60 min (5.77 (0.45); P < 0.001). PMID- 7999500 TI - Reflux during positive pressure ventilation through the laryngeal mask. AB - Patients undergoing anaesthesia for cataract surgery were anaesthetized and their lungs ventilated by intermittent positive pressure ventilation. In one group, ventilation was facilitated by tracheal intubation and in the other group by laryngeal mask airway (LMA). Reflux of stomach contents into the oesophagus was monitored continuously using an indwelling oesophageal pH electrode. The number of discrete episodes of reflux was higher in the LMA group (P = 0.0178), as was the incidence of reflux at antagonism of neuromuscular block (P = 0.0349). PMID- 7999501 TI - Meningitis after combined spinal-extradural anaesthesia in obstetrics. AB - We report two cases of meningitis which developed after combined spinal extradural procedures for obstetric analgesia. The first case was thought to be caused by aseptic or chemical meningitis and the second was a case of bacterial meningitis in a patient who also received an extradural blood patch. It is important that meningitis is considered as a differential diagnosis in patients who present with headache after spinal anaesthesia and that antibiotic therapy is selected to cover unusual organisms. PMID- 7999502 TI - Post-sacral extradural catheter abscess in a child. AB - A 4-yr-old child with hypospadias had a 20-gauge sacral extradural catheter inserted for perioperative analgesia. The catheter was removed 29 h after operation. Ten days after operation a skin pustule was noted at the catheter site. The pustule discharged, recurred, discharged and then recurred over the next 36-48 h. The abscess and tract were then explored under general anaesthesia: curettage was performed and some fatty material sent for culture. No growth occurred from the specimen. Antibiotics were given and resolution followed without further problem. PMID- 7999503 TI - Tracheal rupture after tracheal intubation. AB - Tracheal rupture is a rare complication of tracheal intubation. We present a case of tracheal rupture which was diagnosed 20 h after a smooth intubation sequence and uncomplicated anaesthesia. Possible causes are discussed with reference to cases described previously. PMID- 7999504 TI - Extradural infusion analgesia for postoperative pain relief. AB - We describe 4-yr experience providing extradural infusion analgesia in a district hospital for treatment of postoperative pain. A total of 770 patients recovering from major surgery were treated on general surgical wards between April 1989 and March 1993. The results of a retrospective audit showed that pain control, assessed with both a visual analogue scale (VAS score (0-10 cm)) and a verbal rating scale (VRS), was good. At rest, more than 80% of patients scored pain as absent or mild (VAS score 0-3) during the first 24 h, with only 4% experiencing severe pain (VAS score 7-10). On movement, 50% of patients had good pain control (VAS score 0-3) while 20% of patients experienced severe pain (VAS score 7-10). Minor complications such as emetic sequelae and pruritus were common; these conditions were mild and rarely required treatment. Hypotension (< 100 mm Hg) occurred in 34% of patients in the first 24 h. Ventilatory frequencies of 8 b.p.m. or less occurred in 2.6% of patients. Four patients (0.52%) developed severe respiratory depression. These patients demonstrated increased sedation but only one had a low ventilatory frequency. Three patients died while receiving extradural infusion analgesia. PMID- 7999505 TI - Postal survey of paediatric practice and training among consultant anaesthetists in the UK. AB - A postal survey of previous paediatric anaesthetic training, current paediatric experience and management of an infant pyloromyotomy was undertaken among consultant anaesthetists in the UK. A total of 851 questionnaires were returned, giving a response rate of 31%; 352 (41%) consultants had at least one paediatric list each week, 180 (21%) anaesthetized more than one infant less than 6 months old each month and 373 (44%) had obtained more than 6 months' specialist training. Consultants trained most recently had received significantly longer (P < 0.001) specialist training than their senior colleagues: 558 (66%) consultants dealt with infants requiring a pyloromyotomy, 348 with one or two cases annually. Two-thirds preferred to use an i.v. induction technique and less than half used cricoid pressure. Choice of technique was related to the duration of specialist paediatric training and when it was received, but not to current paediatric anaesthetic experience. The results are discussed in relation to recently published recommendations on paediatric anaesthetic services. PMID- 7999506 TI - Inhaled nitric oxide after cardiac surgery. PMID- 7999507 TI - Inhaled nitric oxide after cardiac surgery. PMID- 7999508 TI - Ventilatory response to hypoxia. PMID- 7999509 TI - Risk of aspiration with the laryngeal mask. PMID- 7999510 TI - Influence of droperidol on nausea and vomiting during patient-controlled analgesia. PMID- 7999511 TI - [The European map of hospitalized children]. PMID- 7999513 TI - [Intestinal pseudo-obstruction secondary to systemic neuropathies and myopathies]. AB - The term intestinal pseudo-obstruction, is applied to a group of clinical disorders in which there are obstructive symptoms, in the absence of a mechanical agent, secondary to a disorder of intestinal motility. In this report, we show manometric studies done in four patients, with acute intestinal pseudo obstructions, secondary to von Recklinghausen's neurofibromatosis (VRNF), in two patients, and in one patient with Duchenne's muscular dystrophy (DMD) and in another with Werdnig-Hoffmann's disease (WHD). We studied 24 hours antroduodenal motility, specially during phase 3 of the migratory motor complex (CMM), which showed a neuropathic disorder in one case of von Recklinghausen's disease and a myopathic disorder in patients with Duchenne's muscular dystrophy and Werdnig Hoffmann's disease. We analysed results and conclusions and specially the kinetic action of erythromycin. PMID- 7999512 TI - [Nitric oxide and Hirschsprung's disease: a causal relation biochemically, immunohistochemically and functionally demonstrated]. AB - Hirschsprung's disease may be due to impaired nonadrenergic-noncholinergic inhibitory input in the aganglionic segment of the colon. It has been suggested that nitric oxide (NO) might be the lacking neurotransmitter. Thus, our specific aims were to determine in ganglionic and aganglionic segments: 1. The activity of the NO synthetase (NO-S); 2. The location of this enzyme; and 3. The "in vitro" basal motor activity of the muscle strips and their responses to an NO donor and to an NO antagonist. METHODS: NO synthetase activity was quantified in samples of tissue from both aganglionic and ganglionic segments obtained during surgery in 6 patients with Hirschsprung's disease by the transformation of 14C-L-arginine into 14C-L-citrulline in tissue homogenates. Immunohistochemical staining of the tissues was performed using a polyclonal antibody raised against a peptide sequence of rat brain NO synthetase. Furthermore, in 2 patients we measured "in vitro" the tonic response of muscle strips to an exogenous NO donor (sodium nitroprusside) and to an NO antagonist (L-NAME). RESULTS: NOS activity was undetectable in every aganglionic segment whereas it was present in all ganglionic segments (0.49 +/- 0.09 pmol citrulina/mg.min; mean +/- SE). Immunohistochemically, NO-S was absent in the myenteric plexus of aganglionic segments and it was present in ganglionic segments. "In vitro" basal motor activity of ganglionic segments was normal, with presence of low-frequency contractions (LFC) and summation contraction (SC); in aganglionic segments SC were absent. Sodium nitroprusside induced a marked relaxation (90% from basal) in muscle strips, both aganglionic and ganglionic, precontracted with bethanocol.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7999514 TI - [Videothoracoscopy, laparoscopy and minimal-access surgery]. AB - Since we start our way in endoscopic surgery, a total of 101 procedures (93 by laparoscopy and 8 by thoracoscopy) have been performed. In two cases (splenectomy, lobectomy) the combination with a minimal enlargement of the wall incision let us remove the entire piece and reduce the operatory time. This is the review of our experience. While the 51.5% of the cases concern to the genitourinary system, the 40.5% of the pathology was digestive and only the 8% was thoracic. The age of the patients ranged between 20 days and 17 years with a clear predominance of the boys. Absence of complications and a high grade of success should do laparoscopy and thoracoscopy frequent surgical procedures in any department of pediatric surgery. PMID- 7999515 TI - [Renal volumetric echography in the newborn infant with an agenetic, dysplastic or obstructive contralateral kidney]. AB - In newborn babies with congenital renal pathology type agenesia, dysplasia or obstruction is very important to know if there is intrautero vicariant growing of the contralateral kidney. To find out that we have proceeded to be ultrasound volume measurement of the normal renal unit, as this is a valuable parameter related to compensatory mechanisms. We have studied by ultrasounds 28 renal units (16 right, 12 left) in newborns with contralateral pathology: pyeloureteral stenosis in 10 cases, multicystic kidney in 13 cases, renal agenesia in 3 cases, obstructive ureterocele in 1 case and another one with ureterovesical stenosis. We considered renal function, length of the larger renal axis width and depth of the kidney mass. Renal function was normal in all cases. Analysis of objectives results show a clear difference between the volume of normal Kidneys in children with contralateral pathology and the control group constituted by 42 renal unit in normal newborns without urological pathology. We conclude with the real evidence of compensatory growing of the normal contralateral kidney during intrautero periods. PMID- 7999516 TI - [The prognosis of patients with posterior urethral valves according to the initial treatment and their urodynamic behavior]. AB - Long-term outcome of 35 boys with severe posterior urethral valves is reviewed, with intention to know if the course of renal function depended on initial treatment and bladder dysfunction. Diagnosis was established during the first month in 15 patients, before one year in 16 and later in 4. Surgical management was initially, upper urinary tract diversion (pyeloureterostomy) in 19 patients (group A) and valve ablation in 15 (group B). The average age for closure of temporary urinary diversion was 17 months. Follow-up ranged from 4-19 years (mean 8.3 years). Twenty one patients had a urodynamic study years after initial treatment and this study showed 8 normal bladder, 7 unstable and 6 non-compliant. In group A, at the end of study, 13 patients (70%) have a glomerular filtration of more than 80 ml/min/1.72 m2 while in group B only 6 (37.5%) and average height after treatment was higher in patients of group A. Noncompliant bladders had worst prognosis (66% renal failure) than unstable bladders (25%) and the prognosis was improved in these types of bladders when initial treatment was upper tract diversion. The results of our study suggest that in patients with severe posterior urethral valves, the renal function improved with early diversion (pyeloureterostomy) and irreversible bladder dysfunction worsen the prognosis in these patients. PMID- 7999517 TI - [The coordination of care for the spina bifida patient. 8 years of experience]. AB - We have analyzed some factors which can show the special health care given to spina bifida patients in two periods, from 1971, when the set Hospital was set up, to 1985 and from 1985 to 1991. In 1985 the position of medical coordinator for spina bifida was created, and at the same time, a spina bifida consultancy was set up. This consultancy was created to improve this coordination and to analyze urological problems. In the first period, there were 54 affected in our Hospital. Now there are 68 patients. The most important goal achieved with this coordination is the improvement in the relationship between the patient, family and doctor, based on a personalized attention, even though this is a difficult subject to quantify. Since 1985 we have seen a lower number of visits to the consultancies in general, but mainly in neurosurgery, urology and orthopedics, a mean of 119 in first period and 45 in the second period. The number of consultancy visits has been the same since the consultancy was set up (46 per year). The number of patients admitted to in hospital was also decreasing. The spina bifida consultancy involves only an hours work a week, the urology ward has been integrated into this, and this avoids the handicapped having to attend other specialized wards so often. The consultancy structure lets us send urine analyses results by post or recover the test results on the same day they are done. Analysing the number of X-ray examinations performed on those patients, the coordinators value is evident: we got a lower number of X-ray examinations, especially invasive, e.g. cystographies and urographies, the latter because they have been replaced by echographies. PMID- 7999518 TI - [Early or late orchidopexy? An evaluation of germ cell proliferation by PCNA immune expression]. AB - A immunocytochemical study for detection of proliferating cell nuclear antigen (PCNA) in order to quantify the number of PCNA-positive spermatogonia, and cytophotometric determination of spermatogonial DNA were performed in cryptorchid and control testes. The number of PCNA-positive spermatogonia, and the average DNA content of spermatogonia in the cryptorchid testes were altered from first years of age. These precocious spermatogonial alterations suggest that the early surgical testicular descent doesn't prevent lesions of germ cells. PMID- 7999520 TI - [Stomach volvulus in a female patient with chondrodysplasia punctata]. AB - The case of an 11-year-old girl with a history of chondrodysplasia punctata is reported. She presented with a clinical picture of abdominal pain and vomiting. At surgical intervention an organo-axial gastric volvulus was found and a single derotation was performed. Three weeks after discharge the patient presented abdominal distension and vomiting. In a plain abdominal X-ray film a gastric dilation was appreciated and a new volvulus was detected by means of a contrast radiogram. The diagnosis was confirmed at surgery and a gastropexy was performed without volvulus relapse. PMID- 7999519 TI - [The clinical characteristics of patients with torsion of the testicular and epididymal appendages]. AB - With the aim of describe a typology that will result in a more precise diagnostic which in turn will permit the selection of the most direct method approach, an analysis was made of the clinical characteristics of patients we treated due to the presence of torsion of the testicular and epididymal appendages. A retrospective review was made of 91 patients, taking into account this age, time of appearance, time of evolution, symptoms, physical examination, histological study and effects. The average age was 9.47 years with a greater incidence occurring between the eight and twelve years old. No influence due to a seasonal phase was detected. The time span between the initial appearance of the symptoms and the time of admittance was 39.5 hours, being somewhat less in patients below the age of six. The common symptom was pain. In addition, 58.2% of the patients also suffered scrotal affectation. In 31 patients the hydatid was palpable and in 19 the "blue dot sign" rendered positive. In 83 cases, surgery was done via the scrotum, resulting in the confirmation of the initial diagnosis. The affectation of the left side was more frequent (62.5%). The hospital discharge was possible in less than 48 hours with no visible long-term effects. Thus, we believe that it is possible to almost always make a diagnosis based on the clinical data, and the type of treatment to be applied should be the extirpation of the hydatid to be carried out via the scrotum. PMID- 7999521 TI - [Duplication of the colon: a case report]. AB - We report a new case of intestinal duplication in a child of two years old with acute abdomen. At the laparotomy was found to be due to tubular duplication ascending colon. A resection duplication joined a tract of normal colon where are was performed, with termino-terminal anastomosis. The postoperative course was excellent. PMID- 7999523 TI - [The Committee on the Selection of Scientific Papers. Its usefulness in developing the scientific program for the congresses of the Sociedad Espanola de Cirurgia Pediatrica]. AB - The following report is to appraise the utility of the Selective Committee of Works of the Pediatric Surgery Society as an assessing organ for the Directive Board to develop the scientific program for the annual congress. For this purpose, a revision was made of a four year period (1990-1993), compiling 738 summaries, which focused primarily on the capacity of the communicated message to widen our concept of disease or our diagnostic or therapeutic possibilities. The secondary topic focused on was the way in which the investigation was decided on planned and executed. The last point taken into consideration was the formal aspects of the summary, according to the regulations given to the authors. From the 738 summaries evaluated, 510 were remitted to be presented as oral communications and 228 as posters. From all these, a total of 311 articles were admitted (172 oral communications and 139 posters). The average pointage obtained was 8.22 (maximum: 20). The articles with the highest acceptance were those dealing with experimental surgery and/or clinical investigation (70%), transplantation (665), urology (50.7%), oncology (45.6%), cardiovascular surgery (45.5%) plastic surgery (40.5%), orthopedics (39.1%), digestive-abdominal (36.8%) and maxillofacial surgery (26.3%). In 77.5% of the articles, the study method followed is not specified, in 70.7% there is no description of the results obtained and in 85.4% there is no description of the conclusions. Deducing from the above information exposed, it is necessary to maintain a system of selection of the best communications, which in turn, will guarantee a greater scientific quality in the congresses. PMID- 7999522 TI - [An asymptomatic splenic hamartoma treated by conservative surgery]. AB - We present the case of an 8-year-old boy accidentally diagnosed of a splenic tumor by ultrasound and computed tomography scan of the abdomen. The patient was treated surgically with a conservative surgical technique (wedge resection and splenorraphy). The histologic study revealed a hamartoma and by immunohistologic study a clear differentiation with the splenic capillary hemangioma could be made. PMID- 7999524 TI - Effect of various serotoninergically induced manipulations on audiogenic seizures in magnesium-deficient mice. AB - The aim of our study was to analyse the possible implication of the serotoninergic system in the pathophysiology and the lethality of audiogenic seizures induced by magnesium deficiency, either by decreasing cerebral serotonin (5-HT) levels (p-chlorophenylalanine) or by increasing 5-HT levels in the brain (5-hydroxytryptophan, L-tryptophan, nialamide, fluoxetine). In magnesium deficient mice, the percentages of audiogenic seizures and of fatal seizures were dependent on the time lapse between the p-chlorophenylalanine (PCPA) injection and the audiogenic test. The percentage was at least 24 h after the injection: in OF1 and C57BL/6 strains, PCPA fully protected the mice from seizure occurrence, whereas it only partially protected the animals of the other strains. 5 Hydroxytryptophan caused a decrease in the audiogenic seizures in magnesium deficient OF1 mice as well as in control DBA/2 mice. In contrast L-tryptophan did not reduce the number of wild courses or of clonic and tonic seizures in either the magnesium-deficient OF1 strain or control DBA/2 mice. Nialamide and fluoxetine were only effective in decreasing the numbers of clonic and tonic convulsions of the audiogenic seizure without affecting the wild courses. The combination of nialamide and tryptophan caused a cessation of the audiogenic seizure phases in both magnesium-deficient OF1 and control DBA/2 mice. In contrast, the fluoxetine-tryptophan combination did not have the same effect on magnesium-deficient and non-magnesium-deficient mice. This work showed that the serotoninergic system plays a secondary role in the pathophysiology of audiogenic seizures in magnesium-deficient mice rather than in that of genetically audiosusceptible mice. PMID- 7999525 TI - Serum potassium, hydrogen ion and magnesium: neuromuscular regulation by variation of cation concentration in the extracellular fluid? AB - It is a common clinical observation that changes in serum [K] are frequently associated with changes in serum [H] and/or [Mg]. Thus, hypokalaemia and alkalosis are associated, as are hyperkalaemia and acidosis, and hypokalaemia and hypomagnesaemia. Most investigators would accept that these ions have important roles in the maintenance of neuromuscular excitability. Extracellular potassium exerts its effect by defining the potassium gradient across the cell membrane and therefore the membrane potential in the resting state; magnesium and hydrogen ion 'screen' negative charges on the surface of nerve cells, modulating the local transmembrane potential gradient, to which the voltage-sensitive channels governing the initiation of the action potential respond. It is pointed out here that the changes in ionic concentration observed in pathophysiology are not incompatible with the idea that the associated changes reflect regulatory events in the extracellular fluid designed to preserve excitability. PMID- 7999526 TI - Migraine treatment by oral magnesium intake and correction of the irritation of buccofacial and cervical muscles as a side effect of mandibular imbalance. AB - A previous paper showed a significant decrease in average erythrocyte magnesium level in 79 migraine patients as compared to 55 controls. This paper completes the results of the initial evaluation, with 152 migraine cases and 85 controls. Serum and erythrocyte magnesium determinations show the following results. Mean serum magnesium was 0.82 mmol/litre in migraine patients and 0.85 mmol/litre in controls, P < 0.005. Mean erythrocyte magnesium was 2.04 mmol/litre in migraine patients and 2.32 mmol/litre in controls, P < 0.0005. These results confirm those of the first paper, but show a more significant difference between the means of the two groups for serum magnesium, which was not significant for the lower number of people involved in the previous study. In all migraine cases without exception clinical evaluation showed an abnormal sensitivity of the buccofacial and cervical muscles which was unilateral and homolateral when migraine was unilateral; it was bilateral when migraine was bilateral. The muscles which were the most sensitive to palpation were the sternocleidomastoid, external pterygoid and scalene. These findings show that migraine patients have a magnesium deficit, which, while not constant, is a frequent occurrence. This raises the problem of the relationship between migraine and other disorders characterized by magnesium deficit, such as latent tetany, mitral valve prolapse, and certain allergies. This magnesium deficit probably promotes muscle irritability, especially when a local imbalance factor results in a permanent pathological stimulation. In addition to irritation and hypersensitivity, migraine attacks occur, particularly after stress, digestive, endocrine and neurological problems.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7999527 TI - Effect of intravenous magnesium infusion on salbutamol-induced bronchodilatation in patients with asthma. AB - In vitro experimental data show that magnesium increases beta-receptor affinity to agonists. We studied the effect of a mild increase in serum magnesium level on the bronchial dose-response curve to salbutamol in six patients with asthma (age 54 +/- 3.6 years, FEV1 49.2 +/- 4.9 per cent of predicted), with a normal serum magnesium level, in a double blind placebo-controlled design. The salbutamol dose response curve was obtained on two separate days, starting 30 min after an intravenous infusion of saline or MgSO4 (20 mg/kg over 10 min, followed by 10 mg/kg/h). The baseline FEV1 values and the values after 30 min infusion on the two test days were not significantly different. During MgSO4 infusion, the serum magnesium level increased significantly from 0.86 +/- 0.01 to 1.31 +/- 0.19 mmol/litre after 30 min and 1.29 +/- 0.17 mmol/litre at the end of the study. FEV1 values after salbutamol were significantly higher during MgSO4 than during saline infusion at the low doses of salbutamol: 1480 +/- 253 vs. 1368 +/- 212 ml, P < 0.05, after 5 micrograms, and 1596 +/- 585 vs. 1378 +/- 532 ml, P < 0.01, after 10 micrograms of salbutamol. The maximum increase in FEV1 obtained after the maximum dose of salbutamol (400 micrograms) was not significantly different during saline and MgSO4 infusion. In conclusion, a mild sustained increase in serum magnesium level increases the bronchodilating effect of low doses of salbutamol, possibly through an increased beta-receptor affinity. There was no effect on the maximum bronchodilating effect of salbutamol. PMID- 7999528 TI - Should magnesium therapy be considered for the treatment of coronary heart disease? I. A critical appraisal of current facts and hypotheses. AB - When given at physiological doses, therapy with magnesium corrects the alterations in cellular function resulting from magnesium deficiency, whereas at higher dosages, which induce hypermagnesaemic levels, magnesium possesses pharmacological effects, such as the inhibition of the calcium influx: this may alter the electrophysiological properties of heart cells, decrease catecholamine secretion, influence the synthesis of prostacyclin and/or alter platelet function. The evidence that magnesium deficiency has untoward effects in patients with ischaemic heart disease is only circumstantial and direct proof that magnesium deficiency causes cardiac disorders is at present lacking. A ubiquitous calcium-channel blockade mechanism is the main and well-established way of action whereby magnesium acts at pharmacological levels; other mechanisms may be involved as well but at present remain questionable or unsettled. On the basis of the present knowledge, beneficial effects may thus be expected from high dose intravenous magnesium therapy in the setting of acute myocardial infarction with respect to mortality rates, even when there is concurrent thrombolytic therapy, as recently demonstrated by the large LIMIT-2 study, although this could not be confirmed from the ISIS-4 trial. High dose intravenous magnesium is also a first choice therapy for terminating torsade de pointes ventricular tachycardia but cannot be considered an established therapy for other cardiac rhythm disturbances nor for settings other than acute myocardial infarction in the case of ischaemic heart disease. The preliminary evidence that magnesium deficiency has a high prevalence in patients with ischaemic heart disease and that it may have a detrimental influence on the course of ischaemic heart disease needs to be validated by larger prospective and controlled clinical studies. Magnesium therapy in ischaemic heart disease thus proves a promising approach which, however, requires that the respective pharmacological and physiological effects be distinguished and further delineated and that the type and stage of ischaemic heart disease be characterized. PMID- 7999529 TI - Should magnesium therapy be considered for the treatment of coronary heart disease? II. Epidemiological evidence in outpatients with and without coronary heart disease. AB - In an epidemiological and follow-up survey on 712 patients, 52 subjects with proven ischaemic heart disease were matched with and compared to 52 coronary prone subjects with similar major cardiovascular risk factors (high-risk controls, HR) as well as to 52 patients at low cardiovascular risk (low-risk controls, LR). HR and LR patients were all free of overt ischaemic heart disease. Both the average daily dietary magnesium intake and the 24 h renal magnesium output were slightly higher in HR as compared to LR and ischaemic heart disease patients. No difference could be observed between the three groups with respect to serum magnesium levels, whereas erythrocyte magnesium levels were lower in ischaemic heart disease patients than in LR (P = 0.089) and to HR (P = 0.042). Ischaemic heart disease patients below 60 years had significantly lower erythrocyte magnesium levels than older (> 60 years) ischaemic heart disease patients. Lower erythrocyte magnesium levels in ischaemic heart disease patients were also associated with an increased incidence of cardiac events in the follow up period and with a more unfavourable outcome. A pilot phase 6 month open trial of oral magnesium supplementation in nine ischaemic heart disease patients with low erythrocyte magnesium levels led to significant increases of erythrocyte magnesium in these patients, and to an impressive decrease of anginal attacks and nitrate consumption, as well as to a lesser degree of ST segment depression on surface ECG obtained at exercise testing in seven patients. PMID- 7999530 TI - Antiarrhythmic effect of parenteral magnesium on ventricular tachycardia associated with long QT syndrome. AB - Magnesium deficiency has been linked with cardiac arrhythmias and sudden cardiac death. Antiarrhythmic effects of intravenous magnesium in the patients who are not hypomagnesaemic were mainly demonstrated in the patients with acquired long QT syndrome. Parenteral administration should be considered in this type of ventricular tachycardia, because its use is safe and straightforward. PMID- 7999531 TI - Elemental analysis of tea leaves by atomic spectroscopic methods. AB - The total aluminium, magnesium, zinc, cadmium, iron, copper, calcium, potassium, and phosphorus contents of tea leaves collected in different countries were determined, as were the contents of these elements that could be extracted with hot distilled water. Atomic spectroscopic methods were used. Little difference in elemental composition was found for tea leaves from different sources. The [Mg]/[Al] ratio in the hot aqueous extracts was twice as high as in tea leaves. It is presumed that the aluminium in tea is present in a complex form which has a less unhealthy effect than its free ionic form. PMID- 7999532 TI - Effect of magnesium supplement in a biological medium (milk) on multiple ionic exchangers in a human membrane. AB - The effects of magnesium supplement in a biological medium (milk) diluted in a survival medium (1/20 dilution in Hanks' solution) have been studied on the multiple ionic exchangers in a human membrane, the amniotic membrane, which is a leaky and asymmetrical membrane. In normal milk, the Ca/Mg molar ratio (MR) is equal to 6.0. In this study, this ratio has been modified to between 0.36 and 6.0, with particular attention to MR values of 0.36, 0.6, 1.0, and 2.0. The transamniotic conductance, Gt, is a function of the Ca/Mg MR: Gt decreases when the MR increases from 0.36 to 6.0, with an inflexion point to 0.7. In the human amnion, Gt is the sum of three paracellular components (Gp) and nine cellular components (Gc). The addition of normal milk (MR = 6) or magnesium-supplemented milk (MR = 0.36, 0.6, 1.0 or 2.0) induces variation in 2 Gp (GpNa and GpK) and three cellular conductances (Na+ and K+ channels and Na/Mg exchanger). Among the MR values studied, MR = 0.36 increased all five components. These data show the relationship between magnesium and milk components and the cellular targets of magnesium supplements and define the best Ca/Mg molar ratio in the biological medium. PMID- 7999533 TI - Combined effects of magnesium deficiency and an atherogenic level of low density lipoprotein on uptake and metabolism of low density lipoprotein by cultured human endothelial cells. I. Biochemical data. AB - The effects of magnesium deficiency on uptake and metabolism of low density lipoprotein (LDL) were investigated using human arterial endothelial cells cultured in media containing various concentrations of magnesium (100-1000 microM) and a high concentration of LDL (2 mg LDL cholesterol/ml) labelled with [3H]cholesteryl linoleate. The LDL uptake was time-dependent and increased for up to 8 h in both the magnesium-deficient and magnesium-sufficient treatments. The extent of LDL uptake progressively increased with the decrease in magnesium concentration of the medium. Surface-bound LDL also increased in a similar manner during the incubation but less extensively than the LDL uptake. The majority of radioactivity from internalized LDL was detected in unesterified cholesterol at all time points in both the magnesium deficiency and sufficiency groups. Only small amounts of radioactivity were found in cholesteryl esters. These findings indicate that most LDL taken up by the cells was rapidly hydrolysed but not readily re-esterified. The lack of re-esterification may be due to a relative deficiency of acyl-CoA:cholesterol acyltransferase (ACAT) and the presence of large amounts of unesterified cholesterol. PMID- 7999534 TI - Combined effects of magnesium deficiency and an atherogenic level of low density lipoprotein on uptake and metabolism of low density lipoprotein by cultured human endothelial cells. II. Electron microscopic data. AB - The effects of magnesium deficiency on low density lipoprotein (LDL) transport by cultured endothelial cells with a high concentration of LDL (2 mg of LDL cholesterol/ml) were investigated by electron microscopy and by counting the radioactivity of [3H]-LDL transported across an endothelial monolayer grown on culture plate inserts. Electron microscopic examination showed that the number of pits/vesicles in the apical side was time-dependently increased for 24 h in both magnesium-deficient and magnesium-sufficient groups with the exception of 1 h under magnesium sufficiency. The number of pits/vesicles in the basal side was also increased for 8 h in both groups, though there was a decrease at 24 h in the two groups. No difference between either magnesium group at the same time point was statistically significant. [3H]-LDL transport was also time-dependently increased in both magnesium-deficient and magnesium-sufficient groups. In contrast to the results obtained by electron microscopy, the amount of LDL transported under magnesium deficiency was much larger for 24 h than under magnesium sufficiency. Differences in LDL transport between magnesium groups were statistically significant at 4 and 8 h. This finding indicates that magnesium deficiency increases LDL transport across the endothelial monolayer. The increase may be due to energy-dependent movement across endothelial cells, energy independent movement between cells, or both. However, we conclude that magnesium deficiency increases the energy-dependent LDL transport to some degree since intercellular gap formations were rarely observed in either magnesium group. This LDL transported to the subendothelial space may lead to LDL accumulation and initiate atherosclerosis. PMID- 7999535 TI - Right to nurse. Our survey says.... PMID- 7999536 TI - A children's hospice: philosophy and facility. PMID- 7999537 TI - Primary health care in Nepal. PMID- 7999538 TI - Pressure sores: a search for definition. PMID- 7999539 TI - Night nurses: why are they undervalued? AB - This is the last article in our series of three looking at sleep in hospitals and the role of the night nurse. This article discusses why night nurses sometimes feel they are undervalued and unappreciated by the nursing profession. The application of primary nursing is also reviewed and presented as a possible solution to the overroutinisation of night nursing. PMID- 7999540 TI - Dementia in acute units: aggression. AB - This is the fourth article in a series which looks at how nurses in acute units can manage the behaviour problems presented by people with dementia. This month, the focus is on aggression, a topic which causes nurses extreme concern. The author discusses some of the precipitating factors which can cause a person with dementia to become aggressive while in hospital, then sets out some appropriate management strategies. PMID- 7999541 TI - Managers: who's boss now? PMID- 7999543 TI - A nurse's nightmare. PMID- 7999544 TI - No limits. Money talks: RCN hardship survey. PMID- 7999542 TI - Midwifery: knight blindness. PMID- 7999545 TI - No limits. Books: browse first, buy later. PMID- 7999546 TI - Right to nurse. Claiming the right to nurse. PMID- 7999547 TI - Right to nurse. Harnessing the power to change. PMID- 7999548 TI - Hats off to Angela. PMID- 7999549 TI - Dementia in acute units: communication. AB - This is the second article in our series which looks in detail at one of the most pressing nursing problems of the age--coping with the behaviours of people with dementia in acute care units. The authors analyse the misunderstandings and misperceptions which conspire to build barriers to communication between nurses and people with dementia, and offer some practical advice on how to overcome them. PMID- 7999550 TI - Skin flaps in plastic surgery: an overview. AB - Once the exclusive preserve of the plastic surgery unit, skin flaps are now being seen by nurses in a variety of surgical specialties. The author describes what the different kinds of flaps are, then explains the vital observations and interventions nurses must perform to keep the patient's skin flap viable. PMID- 7999551 TI - Employment of newly registered nurses. PMID- 7999553 TI - Pay. Just desserts. PMID- 7999554 TI - Learning. Battle of wills. PMID- 7999552 TI - Developing nurse education in Kenya. AB - This article describes a six-month project to facilitate educational developments in the School of Nursing at the Nairobi Hospital, Kenya. The project addressed curriculum revision, mentorship, audit of clinical learning environment, developing teaching and assessing skills in qualified staff, establishing a computerised student allocation system, and post-basic and in-service education. The first three will be described in detail, with some reflections on the experience of introducing change in an environment which was both familiar and strange to the author. PMID- 7999555 TI - People's president. Interview by Graham Scott. PMID- 7999556 TI - Further education: paper chase. PMID- 7999557 TI - Health reforms: beneath the surface. PMID- 7999558 TI - Nursing ethics. VI: Particular features (continuing education credit). PMID- 7999559 TI - An immunisation need: the nursing response (continuing education credit). PMID- 7999561 TI - Right to nurse. Learning difficulties. PMID- 7999560 TI - An idea whose time has come. PMID- 7999562 TI - Right to nurse. Unchartered waters. PMID- 7999563 TI - Right to nurse. Sign of the times. PMID- 7999564 TI - Providing quality experiences. PMID- 7999565 TI - Cancer care: an audit of swollen limb measurements. AB - A common and easy method of assessing changes in limb swelling as a result of cancer treatment is to measure arm circumference at regular intervals. To ascertain whether this is a reliable, reproducible and accurate method, a study of five therapists' techniques was carried out. The results indicated that any differences in measurements between therapists were minimal. The author concludes that this therefore is a reliable method but highlights the need for guidelines to be carefully followed. PMID- 7999566 TI - Protecting nurses' mental health. AB - Following the recommendations of the Allitt Inquiry (1), the role of managers in ensuring staff's mental health needs are catered for and that others are protected from any risk posed by a nurse's mental health status has been highlighted. This article reviews the evidence for mental ill health within the NHS and looks at ways of ensuring recommendations are implemented. PMID- 7999567 TI - Defining the roles of lay and nurse caring. AB - In this article, lay and nurse caring relationships are compared in order to understand their similarities and differences. The author attempts to clarify the boundaries between formal and informal caring in order to understand the hidden conflicts within community care and identify how formal care can meet the needs of lay careers more effectively. PMID- 7999568 TI - Communication: you what? PMID- 7999570 TI - Learning disabilities: learning to accept. PMID- 7999569 TI - Midwifery: taking the plunge. PMID- 7999571 TI - AIDS focus. A long and honourable tradition. PMID- 7999572 TI - AIDS focus. Teaching in HIV/AIDS: can nursing cope? PMID- 7999573 TI - AIDS focus. Challenges old and new. PMID- 7999575 TI - A free health service is 'non-negotiable'. Interview by Kate Williams. PMID- 7999574 TI - Holding together: staff support (continuing education credit). PMID- 7999576 TI - Right to nurse. Bin there, done that. PMID- 7999577 TI - Right to nurse. Put it in black and white. PMID- 7999578 TI - Campaigning for continence care. PMID- 7999579 TI - Developing a diabetes assessment tool. AB - This article describes a diabetes assessment tool, the Barraclough Diabetes Nursing Model, which was developed by the author for use by a diabetes specialist nurse (DSN) (1). The tool is designed to assess individual qualities of people with diabetes such as personal strengths, and their desire and motivation to manage their condition. These qualities can then be recognised, promoted and developed, and used to plan nursing care. The author also discusses the potential long-term benefits of the tool. PMID- 7999580 TI - Dementia in acute units: wandering. AB - This is the third article in a series which looks at how nurses in acute units can manage the behaviour problems presented by people with dementia. It concentrates on wandering, and suggests reasons why people with dementia may wander, distinguishes different types of wandering patterns, and gives some pointers for effective management. PMID- 7999582 TI - One minute wisdom. Mind the theory/practice gap. PMID- 7999581 TI - Nurse practitioners in acute care units. AB - The launch of the UKCC's The Scope of Professional Practice and measures to reduce junior doctors' working hours have once again raised debate on what roles are appropriate for nurses. For many, the development of the nurse practitioner role, with its advanced skills and increased levels of autonomy, offers a very desirable template. Much can be learned from the experience of US nurses, and this article describes a relatively recent innovation--the development of the nurse practitioner role in the acute hospital setting. The role is not a physician substitute; rather, it strengthens and promotes a multidisciplinary approach to patient care and presents the nurse with an opportunity to improve the delivery of care provided in the inpatient environment. Most significantly, it remains a nursing role. PMID- 7999583 TI - Mental health: hair today ... gone tomorrow. PMID- 7999584 TI - Supervision: whipping up a storm. PMID- 7999585 TI - Assisted ventilation. II: Psychological and physical care (continuing education credit). PMID- 7999586 TI - Focal vulvitis. PMID- 7999587 TI - Nuclear transcription factors: potential targets for new modes of intervention in skin disease. AB - Many drugs already in use for the treatment of skin disease, including steroids, retinoids, vitamin D derivatives and cyclosporin (CyA), exert effects on gene transcription. In this review we briefly outline how these drugs work, before proceeding to a consideration of how new drugs acting on the transcription process might be used to influence skin disease. PMID- 7999588 TI - Human cowpox 1969-93: a review based on 54 cases. AB - This survey of the clinical and epidemiological features of human cowpox, a rare but relatively severe zoonotic infection, is based on 54 cases, many unpublished, which we have studied since 1969. Patients present with painful, haemorrhagic pustules or black eschars, usually on the hand or face, accompanied by oedema, erythema, lymphadenopathy, and systemic involvement. Severe, occasionally fatal, cases occur in eczematous and immunosuppressed individuals, although cowpox has not yet been reported in anyone infected with the human immunodeficiency virus. Variations in the clinical features are described, and the differential clinical diagnosis of cowpox, parapox, herpes virus, and anthrax infections is discussed. The role of the laboratory in diagnosis is described, and the value of electron microscopy in providing rapid confirmation is emphasized. Care in taking a detailed history will assist in the initial clinical diagnosis, and a history of contact with domestic cats, particularly during July-October, is important. The possible influence of smallpox vaccination on the incidence and severity is discussed and discounted. PMID- 7999589 TI - Cheveux incoiffables--diagnostic, clinical and hair microscopic findings, and pathogenic studies. AB - Three possible mechanisms of the hair shaft abnormality in cheveux incoiffables have been investigated in nine patients. Cheveux incoiffables hairs were found to exhibit a normal distribution of cystine-rich protein within both the cuticle and the cortex, as determined by silver methenamine ultrastructural cytochemistry. Resistance to stretching, at 65% relative humidity and constant temperature, was similar to normal controls. Resistance to bending forces was also assessed, and was equivalent in both groups. On scanning electron microscopy, all patients with cheveux incoiffables demonstrated longitudinal grooving of the hair shaft, and the hairs were triangular or heart-shaped in cross-section. In addition, there appeared to be minimal cuticular weathering. Even hairs of 20-30 cm length showed only minimal cuticular and cortical weathering, compared with normal hair shafts of similar length and diameter. It is possible that the reduced progressive weathering renders the hair shaft more rigid, and could serve to explain the 'stand on end' appearance of the hair which is typical of this condition. However, the characteristic cross-sectional shape of the hair shaft in cheveux incoiffables may render it more rigid and resistant to bending forces. This latter theory has yet to be fully investigated. PMID- 7999590 TI - A clinical and immunological study of Netherton's syndrome. AB - Netherton's syndrome is a rare genodermatosis of unknown cause, which is classified as an ichthyosiform syndrome. A clinical and immunological study of seven patients with Netherton's syndrome illustrates the clinical spectrum of this disorder, the frequent association with atopy, and the absence of consistent immunological abnormalities. Failure to thrive in infancy was a feature in six of the seven patients, and was considered to be life-threatening in three. The skin disease evolved into ichthyosis linearis circumflexa in four of the seven, and the remaining three patients suffered from persistent or recurrent ichthyosiform erythroderma. PMID- 7999591 TI - A clinical and genetic study of X-linked recessive ichthyosis and contiguous gene defects. AB - X-linked recessive ichthyosis (XLI) is caused by a deletion, or mutation, of the steroid sulphatase gene on the distal short arm of the X chromosome (Xp22.3). This region of the X chromosome is particularly susceptible to deletions. Such deletions can occasionally extend to involve neighbouring genes, causing a contiguous gene defect. Therefore, XLI may be associated with Kallmann's syndrome (KS), mental retardation, X-linked recessive chondrodysplasia punctata and short stature. We have reviewed 33 patients with XLI. Nine showed evidence of contiguous gene defects. A further four had neurological deficit sustained at the time of birth. This study highlights the importance of screening patients with X linked recessive ichthyosis for neighbouring genetic disorders and, in particular, the early identification of KS, as delay in diagnosis may lead to infertility and osteoporosis. Parents should be warned about possible obstetric complications due to prolonged labour in future pregnancies. PMID- 7999592 TI - Stimulation of glycosaminoglycan synthesis in cultured fibroblasts by hyperbaric oxygen. AB - In this study we examined the effect of hyperbaric oxygen treatment on the synthesis of glycosaminoglycans by fibroblasts isolated from wounds and normal skin. Fibroblast cultures were exposed to seven treatments of intermittent hyperbaric oxygen, and then metabolically labelled with D-[6-(3)H] glucosamine. Hyaluronic acid and proteoglycan synthesis were determined by measuring the radioactivity precipitated with cetylpyridinium chloride before and after digestion with hyaluronidase. Hyperbaric oxygen treatment resulted in an increased synthesis of hyaluronic acid and proteoglycans by fibroblasts from wounds and normal skin. Overall, the average increase in total glycosaminoglycan synthesis after hyperbaric oxygen treatment was 28%, whereas fibroblast proliferation was decreased by 7%. These results suggest that one of the effects of this treatment on a wound may be to increase the ratio of extracellular matrix to cells. Such a change could have important consequences for cellular activities essential for effective wound healing, such as migration of cells into the wound and control of cell function. PMID- 7999594 TI - Age-related changes in the elastic properties and thickness of human facial skin. AB - Using recently designed, commercially available, non-invasive instruments, we measured the thickness and elasticity of the skin of the face and ventral forearm in 170 women, and evaluated the effects of age and exposure to sunlight. Skin thickness decreased with age in ventral forearm skin, which has limited exposure to sunlight, but increased significantly in the skin of the forehead, corners of the eyes, and cheeks, which are markedly exposed to sunlight. Skin elasticity (Ur/Uf) decreased with age on both the face and forearm. The ratio of viscosity element to elasticity element (Uv/Ue) increased with age at all sites. However, delayed distension (Uv), immediate retraction (Ur), final distension (Uf), and immediate distention (Ue), as individual elements, decreased on the face and increased on the forearm with age. This tendency was more marked after correction for skin thickness. These results suggested the specificity of skin thickness and elasticity in the facial skin. Analysis using a four-element model showed no changes in the elasticity coefficient of Maxwell element on the forearm, but an increase on the face. This indicates quantitative or qualitative changes in elastic fibres in facial skin. Thus, sunlight appears to have a considerable effect on the thickness and physical properties of facial skin. PMID- 7999593 TI - Gelatinase activity during wound healing. AB - The two known mammalian gelatinases, 72- and 92-kDa gelatinase, are extracellular matrix metalloproteinases (MMPs) with a potential role in wound healing. The gelatinase activity as a function of wound age was analysed in tissue extracts of partial- and full-thickness wounds in the skin of pigs, using two assay systems. Total gelatinase activity, assessed using a 3H-labelled gelatin assay, was highest in the early healing phases and then decreased as healing proceeded in both wound types. Gelatin zymography, which distinguishes the activities of the two gelatinases, showed that the 92-kDa (MMP-9) gelatinase essentially followed the same pattern as that of total gelatinase activity, whereas the activity of the 72-kDa gelatinase (MMP-2) remained fairly stable, although it was higher than in uninjured skin, over the experimental period, irrespective of wound type. In conclusion, the two gelatinases appear to have different functions in the wound healing process. The 72-kDa gelatinase (MMP-2) is important during the prolonged remodelling phase, whereas the 92-kDa gelatinase (MMP-9) is linked to the epithelialization process and early repair events. PMID- 7999595 TI - Variation in comedonal antibiotic concentrations following application of topical tetracycline for acne vulgaris. AB - A miniaturized sensitive bioassay was used to detect tetracycline in open comedones following topical twice daily application of 0.22% tetracycline hydrochloride for a minimum of 4 weeks to the facial skin of patients with mild to moderate acne. The lower limit of detection was 4.8 +/- 0.8 ng per comedone or per 10 microliters. Using this method, 111 of 155 open comedones from 15 patients were found to contain a detectable amount of tetracycline, ranging from 1.8 to 156.9 ng per comedone, and between 4.5 and 1140.1 ng per mg comedonal material. There was a significant effect of comedone weight on tetracycline content, with smaller comedones containing proportionately more tetracycline. The Spearman rank correlation coefficient was -0.5619 (P < 0.001). All 111 comedones in which tetracycline was detected contained sufficient drug to inhibit fully antibiotic sensitive propionibacteria. However, conditions favourable to the selection and overgrowth of highly tetracycline-resistant strains (MIC > or = 32 micrograms/ml) prevailed in at least 18.7% (29 of 155) of the comedones tested. PMID- 7999596 TI - Etretinate administration reduces serum propeptide of type I procollagen level in patients with psoriasis. AB - The serum carboxyterminal propeptide of type I procollagen (PICP) level in 26 patients with psoriasis was significantly lower than in control subjects (124 +/- 47 and 224 +/- 78 ng/ml, respectively; P < 0.001). The patients were divided into two groups, those treated with etretinate and untreated patients. PICP levels in the treated group were significantly lower than those in the untreated group (P < 0.001), but there was no difference between the control and untreated groups. In addition, there was a negative correlation between PICP levels and the serum etretinate concentration in treated patients (r = -0.622, P < 0.05). There was no difference between procollagen type III aminoterminal propeptide (PIIIP) levels in patients and controls, nor was there any significant difference between etretinate-treated and untreated patients. In cell culture studies, etretinate dose-dependently (from 10(-9) to 10(-5) M) decreased the PICP concentration in the medium of fibroblasts from both healthy subjects and patients. In osteoblast cell culture, PICP levels were reduced only in a high concentration of etretinate (10(-5) M). However, no change was observed in preadipose cells. Our in vivo and in vitro observations indicated that psoriasis per se did not affect either serum PICP or PIIIP levels, but that etretinate had an inhibitory effect on collagen synthesis by fibroblasts. Hence, the administration of etretinate to psoriatic patients is, at least in part, responsible for the reduction of serum PICP levels in these patients. PMID- 7999597 TI - Systemic glucocorticoids decrease the synthesis of type I and type III collagen in human skin in vivo, whereas isotretinoin treatment has little effect. AB - The effects of systemic glucocorticoid and isotretinoin treatments on type I and type III collagen synthesis in intact skin were investigated by measuring the carboxyterminal and aminoterminal propeptides of type I procollagen, and the aminoterminal propeptide of type III procollagen, in suction blister fluid (SBF), in a study of 27 patients. All three parameters were significantly lower in the SBF of glucocorticoid-treated patients than in controls or patients undergoing treatment with isotretinoin, whereas the latter two groups did not differ significantly from each other. During glucocorticoid treatment, the concentrations of the procollagen propeptides were only about 20% of the corresponding control values, indicating that systemic therapy with prednisone at a dose of 0.48 mg/kg per day almost totally abolishes collagen synthesis in the skin. These results indicate that systemic glucocorticoid treatment suppresses the synthesis of both type I and type III collagen in the dermis, and suggest that many side-effects of these drugs, such as atrophy of the skin, are due to this inhibition. Systemic isotretinoin treatment did not stimulate skin collagen synthesis. Thus, its regenerative effect on connective tissue may be mediated by mechanisms other than direct stimulation of collagen synthesis. PMID- 7999598 TI - Erythemal and therapeutic response of psoriasis to PUVA using high-dose UVA. AB - In PUVA treatment of psoriasis, clinical observation suggests that uninvolved skin is more susceptible to PUVA erythema than lesions of psoriasis. If this is the case, then the efficacy of PUVA treatment might be increased by using localized high-dose UVA restricted to lesional skin. We have therefore studied the erythemal and therapeutic response of psoriasis to PUVA using high-dose UVA and, for comparison, the erythemal response to UVB. In 14 patients, an area of psoriasis and adjacent uninvolved skin were exposed to a series of UVA doses (350 +/- 30 nm, 1-16J/cm2), using an irradiation monochromator. Six other patients were similarly phototested with a series of UVB doses (300 +/- 5 nm, 20-112 mJ/cm2) to both uninvolved and lesional skin. Erythema was judged visually at 72 h for psoralen-UVA, and at 24 h for UVB, and measured using a scanning laser Doppler velocimeter. In 10 patients, PUVA therapy using high-dose UVA was subsequently given to lesional skin (8-16J/cm2 twice weekly) in addition to conventional whole-body PUVA. For psoralen-UVA, the minimal phototoxic dose within psoriasis was increased by a factor of 4 compared with non-lesional skin (P < 0.01, Wilcoxon signed-rank test). For UVB, the minimal erythema dose within psoriasis was higher than that for non-lesional skin (medians > 112 and 28 respectively, P < 0.05). Laser-Doppler measurements confirmed that the reduced erythemal sensitivity was not due to masking of response by pre-existing increased blood flux within psoriasis.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7999599 TI - A comparative study of calcipotriol ointment and tar in chronic plaque psoriasis. AB - The antipsoriatic efficacy, tolerability and safety of calcipotriol ointment was compared with tar in a prospective, right/left randomized, investigator-blinded controlled study. Calcipotriol ointment 50 micrograms/g twice daily was applied to one-half of the body. On the opposite side, white soft paraffin was applied in the morning, and coal tar solution BP 15% v/w in aqueous cream in the evening. Thirty patients with stable chronic plaque-type psoriasis were recruited. Assessments were made at 2, 4 and 6 weeks. Three patients were withdrawn from the study. A decrease in PASI score was seen on both sides at 2, 4 and 6 weeks. The differences from baseline between the two treatments were statistically significant in favour of calcipotriol. Improvement with calcipotriol was rapid in the first 2 weeks of treatment. With tar, significant improvement occurred only after 4 weeks of treatment. The differences in the scores for erythema, induration and desquamation from baseline between the two treatments were also statistically significantly in favour of calcipotriol at all evaluation points. Seven patients developed irritation on the calcipotriol-treated side, but there were no adverse effects on the tar-treated side. In two patients, itching associated with psoriasis was reduced by the calcipotriol. Although the mean serum calcium and phosphate levels remained within the normal ranges after 6 weeks' treatment, there were significant changes in their values compared with baseline. PMID- 7999601 TI - One-week therapy with oral terbinafine in cases of tinea cruris/corporis. AB - The use of oral terbinafine in the treatment of superficial dermatophyte infections has been extensively studied, using different treatment regimens. To evaluate the efficacy of short-term therapy with oral terbinafine in cases of tinea cruris/corporis, 22 patients (21 male and one female) with mycologically proven tinea cruris/corporis, were included in the present study. Each patient received one tablet of terbinafine 250 mg daily for 1 week. Patients were followed-up for 6 weeks after completion of treatment. Clinical and mycological assessments were performed at the end of treatment, and at the end of the follow up period. The mean sum of scores of signs and symptoms in all patients decreased significantly from 12.36 before treatment to 0 at the end of the follow-up period, and mycological investigations were negative in all patients at the end of the follow-up period. Our results show that 1-week therapy with oral terbinafine is highly effective in the treatment of tinea cruris/corporis. PMID- 7999600 TI - Comparative effects of calcipotriol solution (50 micrograms/ml) and betamethasone 17-valerate solution (1 mg/ml) in the treatment of scalp psoriasis. AB - The efficacy, tolerability and safety of calcipotriol solution and betamethasone 17-valerate solution were compared in a multicentre, prospective, randomized, double-blind, parallel group study. Four hundred and seventy-four patients with scalp psoriasis were recruited from six European countries and Canada. Following a 2-week washout period, either calcipotriol solution (50 micrograms/ml) or betamethasone 17-valerate solution (1 mg/ml) was applied twice daily for 4 weeks. After this time, patients who required no further active treatment were observed for relapse. Retreatment with calcipotriol was offered to those patients who relapsed, and who were originally in the calcipotriol-treated group. The two treatment groups were well matched at baseline. At the end of treatment, the proportion of patients who had 'cleared' or 'markedly improved' was statistically significantly greater in the betamethasone group (75%) than in the calcipotriol group (58%) (P < 0.001) (95% confidence interval of difference 25.3-->8.6). The decrease in total sign score (sum of scores for erythema, thickness and scaliness) at the end of treatment was also statistically significantly greater in the betamethasone group (61%) than the calcipotriol group (45%) (P < 0.001) (95% confidence interval of difference 9.7-->23.1). Adverse events were reported by 87 patients in the calcipotriol group, and 31 patients in the betamethasone group; the most common was lesional or perilesional irritation, which occurred significantly more frequently with calcipotriol (26%) than with betamethasone (8%) (P < 0.001). Fifteen patients (6%) in the calcipotriol group and four (1%) in the betamethasone group withdrew from the study because of adverse events or unacceptable treatment response (P = 0.017).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7999602 TI - Acrodermatitis chronica atrophicans: a case report and review of the literature. AB - We report a 55-year-old woman with acrodermatitis chronica atrophicans (ACA) and a peripheral sensory neuropathy. ACA is an uncommon late cutaneous manifestation of Lyme disease, which follows disseminated Borrelia burgdorferi infection. This is the second published case from the U.K. since serological diagnosis has been available. In this patient the diagnosis was confirmed by serology using a sensitive enzyme-linked immunosorbent assay and immunoblotting techniques. B. burgdorferi DNA was demonstrated in the affected skin using the polymerase chain reaction, although staining and cultures for the organism were negative. Recommended treatment of ACA is with oral doxycycline 100 mg twice daily for 28 days, but our patient did not respond well to this regimen. She was therefore treated with ceftriaxone intravenously for 21 days, which resulted in a rapid symptomatic and clinical response. PMID- 7999604 TI - Squamous cell carcinoma arising in vulval lichen planus. AB - We report two cases of squamous cell carcinoma arising in vulval lichen planus. Patients with lichen planus should be examined for evidence of genital involvement. If this is present, such patients should be closely monitored, and any atypical lesions biopsied. PMID- 7999603 TI - A case of bullous pemphigoid with antidesmoplakin autoantibodies. AB - Paraneoplastic pemphigus, a recently identified disease entity, is associated with autoantibodies against a variety of epidermal proteins including desmoplakins I and II, and the 230-kDa bullous pemphigoid (BP) antigen. We report an 84-year-old Japanese man who had typical clinical and histopathological features of BP, but in whom indirect immunofluorescence, using normal human skin as the substrate, revealed concomitant serum antibasement membrane zone and antikeratinocyte cell surface autoantibodies. His serum showed reactivity similar to that which is seen with antidesmoplakin monoclonal antibody on immunofluorescence of cardiac muscle and urinary bladder. With immunoblotting, using various antigen sources, the patient's serum reacted with desmoplakins I and II, and with both the 230- and 180-kDa BP antigens. Immunogold electron microscopy also indicated the presence of antidesmoplakin antibodies. Although the significance of the antidesmoplakin antibodies in this patient is unknown, the findings in this case may provide an insight into understanding the occurrence of antidesmoplakin antibodies in paraneoplastic pemphigus. PMID- 7999605 TI - Acquired progressive lymphangioma. AB - Acquired progressive lymphangioma (APL) is a rare, benign proliferation of lymphatic capillary origin, which is characterized histologically by dermal vascular channels and a 'dissection of collagen' appearance. We describe a 30 year-old patient with an extensive, refractory APL on the right breast, which slowly developed over a period of 23 years. Pathologists and dermatologists should be aware of this entity, as early surgical treatment may be totally curative when the lesion is limited in size. PMID- 7999606 TI - Bullous lymphoma of the skin. AB - We describe an extremely rare case of cutaneous B-cell lymphoma associated with bulla formation. The term, 'bullous lymphoma' is proposed for this variant of cutaneous lymphoma. PMID- 7999607 TI - Darier's disease: severe eczematization successfully treated with cyclosporin. PMID- 7999608 TI - Juvenile pityriasis rubra pilaris associated with hypogammaglobulinaemia and furunculosis. AB - We report a case of follicular keratosis with inflammatory changes, consistent with a diagnosis of atypical juvenile pityriasis rubra pilaris. An unusual feature was the occurrence of severe Staphylococcus aureus folliculitis and furunculosis, a phenomenon rarely encountered in pityriasis rubra pilaris and the other follicular keratoses. Standard antibiotic and antiseptic treatment for chronic S. aureus infection was ineffective. The patient was subsequently found to have hypogammaglobulinaemia, and treatment with human polyvalent immunoglobulin infusions was successful in eradicating the sepsis. It is therefore probable that the hypogammaglobulinaemia played a pathogenic role in the development of cutaneous sepsis. PMID- 7999609 TI - Midborderline (BB)-borderline lepromatous (BL) leprosy with reversal reaction (RR). PMID- 7999610 TI - Mycosis fungoides and polyarthritis. PMID- 7999611 TI - Mycetoma. PMID- 7999612 TI - Psoriasis and filariasis. PMID- 7999613 TI - Epidermolysis bullosa acquisita. PMID- 7999614 TI - Comel-Netherton syndrome. PMID- 7999615 TI - VIN III (bowenoid type) and HPV infection. PMID- 7999616 TI - Curettage of small basal cell papillomas with the disposable ring curette is superior to conventional treatment. PMID- 7999617 TI - Severity of atopic dermatitis in India. PMID- 7999618 TI - 'I'll have mine with a twist of lemon'. Quinine photosensitivity from excessive intake of tonic water. PMID- 7999619 TI - Alopecia areata responding to immunoglobulin, with varying response to different preparations. PMID- 7999620 TI - Eosinophilic pustular folliculitis responding to cyclosporin. PMID- 7999621 TI - Plasminogen activator inhibitor 1 (PAI-1) levels in patients with chronic venous leg ulceration. PMID- 7999623 TI - Ultraviolet radiation and skin cancer--keep your top on? PMID- 7999622 TI - Androgens and sweating. PMID- 7999624 TI - Joint occurrence of human papillomavirus type 16 DNA in Bowen's disease on a finger and in dysplasia of the vulva and the uterine cervix. PMID- 7999625 TI - Beneficial effect of a combination of retinoids and long-acting theophylline in the treatment of psoriasis vulgaris. PMID- 7999627 TI - Congenital dysmorphism of finger and toenails associated with acro-osteolysis. PMID- 7999626 TI - No change in skin innervation in patients with palmar hyperhidrosis treated with tap-water iontophoresis. PMID- 7999628 TI - Pachydermodactyly or acquired digital fibromatosis. PMID- 7999629 TI - The Koebner phenomenon and AIDS-related Kaposi's sarcoma. PMID- 7999630 TI - Verrucous skin lesions on the legs of leprosy patients. PMID- 7999631 TI - British Connective Tissue Society Meeting. Sheffield. PMID- 7999632 TI - Cell kinetics and polyamine enzymes in the intestinal mucosa of rats with azoxymethane induced tumours. AB - We studied the proliferative activity and the modifications in ornithine decarboxylase (ODC) and diamine oxidase (DAO), enzymes involved in polyamine metabolism, in the apparently normal intestinal mucosae of rats with azoxymethane induced tumours. Fifty rats were treated with six weekly injections of 15 mg/kg body weight azoxymethane (AOM). Six rats died during the treatment. All the surviving rats developed intestinal tumours; tumour incidence was 93.1% (41/44) in the left colon, 40.9% (18/44) in the right colon and 45.4% (20/44) in the small bowel. In the normal-appearing mucosa close to intestinal tumours we found an extension of the normal proliferative compartment to the upper third of the crypts (stage I abnormality) and a shift of most of the DNA synthesizing cells from the basal region to the middle and upper third (stage II abnormality). Furthermore, the intestinal mucosa characterized by proliferative abnormalities showed an ODC activity significantly higher than the normal mucosa of control rats (small bowel: 1.01 +/- 0.26 vs 0.42 +/- 0.15, P < 0.01; right colon: 1.32 +/ 0.34 vs 0.25 +/- 0.02, P < 0.001; left colon: 1.93 +/- 0.35 vs 0.22 +/- 0.01, P < 0.01). We also detected a significant decrease of DAO activity in the mucosa of the small bowel and right colon of treated rats compared to controls (0.86 +/- 0.09 vs 4.39 +/- 0.85, P < 0.01; 1.04 +/- 0.43 vs 3.80 +/- 0.91, P < 0.01, respectively), while DAO activity in the left colon was unchanged. The lower incidence of tumours in the small bowel and right colon suggests the presence of factors protecting these segments from carcinogenesis.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7999633 TI - Expression and localization of sulphated glycoprotein-2 mRNA in the rat incisor tooth ameloblasts: relationships with apoptosis. AB - The expression of sulphated glycoprotein-2 (SGP-2) is associated with the onset of cellular atrophy and death in many rodent tissues. This gene has a multifunctional involvement that includes apoptosis, spermatogenesis, promotion of cell-cell interactions, modulation of complement systems and tissue regeneration and remodelling. Using decalcified mandibles, mRNA for SGP-2 in rat incisor tooth ameloblasts was examined by in situ hybridization using 35S riboprobes. The rat incisor is unique in that, at one time, all stages of the complex life cycle of the ameloblasts are represented along the length of the enamel forming aspect of the tooth. The pre-ameloblasts only secrete enamel matrix after mitosis. When the full thickness of the enamel has been formed, a remarkable transition in phenotype takes place in the ameloblast. This transition is accompanied by apoptosis or programmed cell death of approximately 25% of ameloblasts. An additional 25% of ameloblasts undergo apoptosis when maturation of enamel matrix takes place with removal of water and protein from the increasingly mineralized matrix. In the present study, expression of SGP-2 was localized most often in the post-secretory transition and maturation ameloblasts. In contrast, the presecretory and secretory ameloblasts did not demonstrate specific hybridization signals. Consistently, neither the odontoblasts nor the pulp demonstrated hybridization signals. Hence our results support other published results which show that increased expression of SGP-2 is associated with apoptosis. The exact function of the SGP-2 gene and its products is not fully defined.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7999635 TI - The development of the endothelin-1-induced gastric ulcer: time sequence analysis of morphologic changes. AB - We have recently reported that the submucosal injection of endothelin-1 induces gastric ulcers in rats. In the present study, we have examined the time sequence of the macroscopic, histologic and ultramicroscopic features of the formation and development of the gastric ulcer induced by endothelin-1 (100 pmol submucosally). In rats, we examined the effect of endothelin-1 on the gastric mucosa macroscopically, on the gastric mucosal cells and vessels by light microscopy and on the ultra-structure of the gastric mucosal surface and of the gastric glands by electron microscopy. Gastric mucosal changes were evaluated 1, 4, 30 minutes, 1, 4, 8, 16, 20, 24 hours and 2, 4, 7, 14, 21 days after teh submucosal injection of endothelin-1. Application of endothelin-1 was immediately followed by arterial vasoconstriction and venous dilatation, 5 minutes later by interstitial haemorrhage and 30 minutes later by demise of epithelial cells. Electron microscopy showed almost complete exfoliation of the inter-pit cells 30 minutes after the injection. By 1 hour, superficial redness, apoptosis of superficial cells and loss of the intra-pit cells was detected. By 8 hours, there was mucosal haemorrhage and complete loss of intra-pit cells from the basal part of the gastric glands. Forty-eight hours later, there was a deep gastric ulcer with penetration of the muscularis mucosae. By 4 days, the ulcers had entered the chronic phase and by 1 week abnormal glands were covering the area of damage with no mucous production. By 3 weeks the damaged area was still structurally abnormal. The results of this study suggest that injury to the microvasculature may initiate the degenerative and structural changes of the gastric mucosa that lead to the production of this novel type of experimental gastric ulcer in rats. PMID- 7999634 TI - Immunohistochemical and biochemical indicators of muscle damage in vitro: the stability of control muscle and the effects of dinitrophenol and calcium ionophore. AB - The biochemical, histological and ultrastructural effects of 2,4-dinitrophenol and the calcium ionophore, A23187, on rat soleus muscle incubated in vitro have been examined to test the hypothesis that immunohistochemical techniques can be used to recognize early structural features of fibre damage. In control muscles, despite mild glycogen depletion and a mild reduction in protein synthetic rate in the central portion of the muscle, fibres throughout the muscle appear to be viable with normal cytoskeletal and contractile protein architecture, normal concentrations of high energy phosphates and no creatine kinase efflux. Dinitrophenol causes rapid creatine kinase efflux, extensive loss of immunolabelling for desmin and dystrophin, and abnormal myosin immunolabelling. Creatine kinase efflux and the changes in desmin and dystrophin are reduced by the exclusion of calcium. A23187 causes more gradual creatine kinase efflux associated with changes in myosin immunolabelling, but loss of desmin and dystrophin immunolabelling is restricted to a few of the most peripheral fibres. The results suggest that immunohistochemical methods can be used to reveal differences in the intracellular mechanisms of muscle damage. Although both dinitrophenol and A23187 may act, in part, through calcium-mediated processes, their effects on cytoskeletal proteins differ. Creatine kinase efflux after A23187 may not be due to gross sarcolemmal damage. PMID- 7999636 TI - The myocardial effects of fenoterol, isoprenaline and salbutamol in normoxic and hypoxic sheep. AB - Three groups, each of four sheep, were randomly allocated under blinded conditions to receive the beta-adrenoceptor agonists, salbutamol, fenoterol or isoprenaline, in doses of 0.5, 2, 8, 32 and 128 micrograms/kg intravenously at 15 minute intervals. A separate group of four animals received equal volumes of saline. Heart rate was recorded immediately prior to each drug administration and serum potassium was measured. Three to 4 days later the experiment was repeated during induced systemic hypoxia and the animals then necropsied. All the agonists produced significant increases in heart rate. During hypoxia, lower heart rates were recorded than in the normoxic experiments. Under conditions of hypoxia, all the beta-agonists produced significant hypokalaemia. Sterile saline had no effect on either heart rate or serum potassium levels. At necropsy, myocardial lesions were found in animals receiving all three beta-agonists. Subendocardial haemorrhage was consistently seen in all animals receiving fenoterol. Multifocal myonecrosis of 3-4 days duration was present in the left ventricle of all animals receiving fenoterol, in two receiving isoprenaline and in two receiving salbutamol. The lesions were most severe in the papillary muscle and were visible grossly in one animal given fenoterol and one given isoprenaline. No lesions were found in the control animals. PMID- 7999638 TI - Effect of animal age on the uptake of large particulates across the epithelium of the rat small intestine. AB - A quantitative investigation into the transfer of latex polystyrene particles across the epithelium of the small intestine has been carried out using male weanling, adult and aged Sprague-Dawley rats. Orally administered polystyrene particles, 2 microns in diameter, were transferred from the lumen of the small intestine into the gut associated lymphoid tissues (Peyer's patches). No significant difference in the number of particles transported across the gut epithelium was detected between animals of different age groups. The concentration of particles detected in Peyer's patches excised from the proximal and distal regions of the small intestine of particle-treated animals did not differ significantly, except in aged rats. Particle concentration was significantly higher in Peyer's patch tissue than in adjacent Peyer's patch-free tissues of the small intestine in treated animals of all age groups. The assay method described here may be used for quantitative investigation of the transepithelial transport of large particulates. PMID- 7999637 TI - Interferon-gamma and polyunsaturated fatty acids increase the binding of lipopolysaccharide to macrophages. AB - We have previously shown that interferon-gamma (IFN-gamma) increases the polyunsaturated fatty acid content of membrane phospholipids in cells that were sensitive to endotoxin. In this study, IFN-gamma was found to stimulate the binding of endotoxin to the murine macrophage cell line J774.2 and the human monocyte cell line U937. Interferon-gamma-activated J774.2 cells showed a 66% increase in fluoresceine isothiocyanate (FITC) labelled LPS binding (P < 0.0005 vs control cells) and a 49% increase in tritium labelled LPS binding (P < 0.0001 vs control cells). Interferon-gamma also induced a 35% increase in binding of FITC-LPS in U937 cells (P < 0.0001 vs control cells). In contrast, pretreatment of J774.2 cells with interferon-beta (IFN-beta) had no effect on binding of FITC LPS. Preincubation with exogenously supplied polyunsaturated fatty acids, linoleic and arachidonic acids, resulted in increases of 74% and 69% in FITC-LPS binding, respectively (both P < 0.0005 vs control cells). On the other hand, pretreatment with the saturated fatty acid, palmitic acid, had no effect on FITC LPS binding. We propose that IFN-gamma-induced changes in the membrane phospholipid fatty acid composition of macrophage-like cells influence the binding of endotoxin. PMID- 7999639 TI - Erythropoiesis in mouse omental milky spots induced by erythropoietin: light and electron microscopic study. AB - The mouse omentum contains omental milky spots. They are abundantly present particularly in the omental fat band. In normal mice, the milky spots are composed of abundant lymphocytes/plasma cells with macrophages, granulocytes and various stromal cells. Unlike the lymph node, they show occasional neutrophilic myelopoiesis, though neither erythropoiesis nor megakaryopoiesis is present. We investigated the haematopoietic ability of the milky spots in ddY mice by administering intraperitoneal injections of erythropoietin (EPO), 500 units/body/day for 7 consecutive days. The omental fat bands were removed the day after the last EPO injection, and the milky spots were examined by light and electron microscopy. Small clusters of erythroblasts appeared in the milky spots in mice injected with EPO. In these clusters, erythroblasts in various maturation stages, dividing erythroblasts, denucleating erythroblasts and reticulocytes were seen by electron microscopy. These findings suggest that such clusters represent erythropoietic foci. The presence of erythropoietic foci in the milky spots was confirmed in all the mice injected with EPO. Megakaryocytes did not appear in the milky spots. These findings suggest that the milky spots have a latent erythropoietic ability, as well as active neutrophilic myelopoiesis. PMID- 7999640 TI - Doppler radar velocity measurements for wound ballistics experiments. AB - Bullet velocity is a basic parameter in wound ballistics studies. It is usually measured electronically by means of a variety of solid or photoelectric barriers connected to equipment measuring the time elapsing between impulses, enabling the velocity to be calculated. With the advent of Doppler radar velocity measurement of large calibre artillery shells, the use of this equipment for wound ballistics experiments was investigated. Anaesthetized pigs were shot at a range of 9-10 metres and the velocities measured by Doppler radar and photocells were compared. A very good correspondence between the measured entry and exit velocities in low and medium velocity bullets was found, i.e. an average deviation of less than 1% (range 0-2%) between the two types of equipment. In high velocity bullets measurement of entry velocities was just as good, but in both methods measurement of the exit velocity was complicated by the cluttering of signals by fragments of tissue released from the exit wound and the deflection of the bullet, Doppler radar offers important benefits - simple set up, minimal risk of damage of equipment by stray bullets and very good accuracy - and may replace photocells and similar equipment in studies involving low and medium velocity bullets. Measurement of the exit velocity of high velocity bullets is unsatisfactory in both methods, and it is necessary to improve the Doppler radar method in order to measure that as well. PMID- 7999641 TI - Variation in short tandem repeat sequences--a survey of twelve microsatellite loci for use as forensic identification markers. AB - Alleles at 12 Short Tandem Repeat loci have been sequenced to investigate candidate loci for a multiplex Short Tandem Repeat system for forensic identification, and for single-locus amplification of Short Tandem Repeat loci. Variation from the consensus sequence was found at 6 loci, while one locus, D21S11, was found to be complex in sequence. The presence of non-consensus alleles does not rule out loci for inclusion as forensic identification markers, but size differences between alleles of 1 base pair require very precise sizing. We suggest criteria for the suitability of Short Tandem Repeat loci as forensic identification markers, and propose a universal allele nomenclature for simple and compound Short Tandem Repeats. The effect of the repeat unit sequence of the evolution of Short Tandem Repeats is discussed. PMID- 7999642 TI - A rapid method for detecting barbiturates in serum using EI-SIM. AB - A simple and rapid method for analysis of barbiturates in serum has been developed. In order to extract and clean barbiturates in serum, a separation column packed with Extrelut and Florisil was used, and the eluate was directly analyzed by means of electron impact selected ion monitoring (EI-SIM). Selected ions used were base peak ions of 10 barbituartes, and the internal standard used was allobarbital or secobarbital. The calibration curves were linear over the range 0.5-5 ng. Extraction of replicate serum samples containing 20 micrograms/1.5 ml and 5 micrograms/1.5 ml resulted in a recovery of 87.2-105.2% and 81.6-104.6%, respectively, with the exception of phenobarbital, which was 151.9% and 172.1%, respectively. Secobarbital was also analyzed in the serum of 13 patients who had been given secobarbital intravenously. In 3 out of 10 cases, secobarbital levels greater than 1 micrograms/ml were detected more than 72 h after administration. This method seems to have possibilities for clinical use. PMID- 7999643 TI - Swiss population data on three tetrameric short tandem repeat loci--VWA, HUMTHO1, and F13A1--derived using multiplex PCR and laser fluorescence detection. AB - Allele and genotype frequencies for 3 tetrameric short tandem repeat loci VWA, HUMTHO1, and F13A1 were determined in a Swiss population sample using multiplex PCR and subsequent electrophoresis in DNA sequencing gels processed by automated laser fluorescence detection. The technique allows single base pair resolution and rapid typing, with a concomitant reduction in the potential for human transcriptional typing errors. All loci meet Hardy-Weinberg expectations. In addition, there is little evidence for association of alleles among the 3 loci. The allelic frequency data can be used in forensic analyses and paternity tests to estimate the frequency of a multiple STR locus DNA profile in the Swiss population. PMID- 7999644 TI - Application of a simple enzymatic digestion method for diatom detection in the diagnosis of drowning in putrified corpses by diatom analysis. AB - The reliability and applicability of quantitative and qualitative diatom analysis by an enzymatic digestion method in the diagnosis of drowning of putrified bodies has been evaluated. The authors report the analysis of water and organ samples of 12 immersion cases using light microscopy. This study included control organ samples from the bodies of persons who died from causes other than drowning. Organ samples were treated by both chemical and enzymatic methods, the first one using concentrated nitric acid and the second proteinase K. Diatoms were present in most organ samples of the immersed corpses; no diatoms could be found in the control samples. Our experience was that the enzymatic method seemed to be more convenient in terms of rapidity, safety and environmental protection than chemical digestion. The number of diatoms recovered with both methods was similar. Qualitative and quantitative analysis of both water and organ samples of immersion cases supported the diagnosis of death by drowning in 41.6% of the putrified cases studied. The authors suggest that diatom analysis using enzymatic digestion of organs can be used as a criterion for positive diagnosis of drowning in cases involving putrified bodies. PMID- 7999645 TI - Estimation of time of death by quantification of melatonin in corpses. AB - A method for the estimation of time of death (TOD), was evaluated by measuring the melatonin (MT) content of pineal bodies (PBs), sera and urine samples from 85 cadavers. A total of 44 cadavers were investigated in Sapporo (geographical coordinates N 43 degrees 4', E 141 degrees 21') and 41 in Tokyo (N 35 degrees 39', E 139 degrees 44'). MT contents were measured by radioimmunoassay (RIA) in 75 PBs, 27 sera and 14 urine samples. Exponential differences of pineal MT content were recognized between peaks in nighttime and nadirs in daytime, ranging from 0.099 to 63.2 ng/PB. Circadian rhythms were also observed for the concentrations of MT in serum (11-205 pg/ml), and in urine (7.5-137.5 pg/ml). Consequently, criteria for the TOD estimation are proposed as follows. 1) Pineal MT contents--(1) 0-0.2 ng/PB: TOD 1100-1700 hours, (2) 0.2-0.3 ng/PB: TOD 0700 2000 hours, (3) 0.3-1 ng/PB: inconclusive, (4) 1-4 ng/PB: TOD 1600-1000 hours, (5) 4-8 ng/PB: TOD 2000-0800 hours, (6) over 8 ng/PB: TOD 2000-0500 hours, 2) Serum MT concentration--(1) 0-100 pg/ml: inconclusive, (2) over 100 pg/ml: TOD 2200-0100 hours, and 3) Urinary MT concentration--(1) 0-35 pg/ml: inconclusive, (2) over 35 pg/ml: TOD 1800-0600 hours. The range of the estimation can be limited by a combination of these 3 criteria. The present method can be combined with other methods for estimating the TOD to decrease the range. PMID- 7999646 TI - Haptoglobin subtypes in the East Midlands (United Kingdom). AB - Haptoglobin subtypes were analysed by isoelectric focusing (IEF) in 5 regional populations from the East Midlands (United Kingdom). The allele frequencies showed a considerable variation at regional level. Allelic frequency ranges were HP*1S = 24-28%, HP*1F = 11-15%, HP*2FS 54-63%, HP*2SS = 0.5-6% and HP*2FF 0-1%. The data presented here suggest that HP subtypes provide a useful genetic marker for population studies and paternity testing. PMID- 7999647 TI - Occurrence of HIV-antibodies among drug abuse-related fatalities in major European cities (up to December 31st, 1992) PMID- 7999648 TI - Toxicological analysis of drugs and poisons in formalin-fixed organ tissues. 2. Volatile substances. AB - Diethylether, chloroform and toluene were administered by inhalation and ethanol intravenously to rabbits. As soon as possible after death, tissue specimens were collected from the brain, lung, liver, kidney and skeletal muscle and fixed in non-buffered 10% formalin at room temperature (10-20 degrees C) for 4 different periods (1, 2, 5 and 14 days). The volatile substances were analyzed and identified by gas chromatography/mass spectrometry (GC-MS). The measured concentrations of ethanol, diethylether, chloroform and toluene in the brain tissue 1 day after fixation decreased to 8, 23, 73 and 84% respectively compared with those in the non-fixed brain tissue (100%). The rank order of the rate of decrease in the fixed state was: ethanol > diethylether >> chloroform > toluene. These volatile substances could be detected clearly in all the tissue specimens, even after a 14-day fixation period. These results provide useful toxicological information that will help to differentiate whether volatile substances have been administered antemortem or postmortem. PMID- 7999649 TI - Safety in numbers. The role of pharmacokinetics in local anesthetic toxicity: the 1993 ASRA Lecture. PMID- 7999650 TI - Plasma concentration profile of epidural alfentanil. Bolus followed by continuous infusion technique in the parturient: effect of epidural alfentanil and fentanyl on fetal heart rate. AB - BACKGROUND AND OBJECTIVES: A combined bolus and continuous epidural infusion technique of opioid and bupivacaine mixture has been described, although no pharmacokinetic data for this technique exists. The study documents the plasma concentration profile of epidural alfentanil in parturients using this technique, and evaluates the fetal heart rate tracing for associated changes following opioid administration. METHODS: Twenty-four subjects were randomized to receive epidural alfentanil 500 micrograms in 10 mL 0.125% bupivacaine, group A, or fentanyl 50 micrograms in 10 mL 0.125% bupivacaine, group B, as a bolus dose, followed by continuous infusions of alfentanil 20 micrograms/mL in 0.125% bupivacaine (group A) or fentanyl 2 micrograms/mL in 0.125% bupivacaine (group B) for labor analgesia. Plasma drug levels for each group were examined using repeated measures analysis of covariance. RESULTS: Fetal heart rate tracings were recorded throughout the study and were retrospectively analyzed by a "blinded" perinatologist. Data from fetal heart rate tracings were examined by repeated measures analysis of variance. Mean infusion rates were 9.3 +/- 2.1 mL/hour and 9.6 +/- 1.7 mL/hour for groups A and B, respectively. Mean study duration was 3.7 hours in group A, and 3.0 hours in group B. Low plasma levels precluded analysis of fentanyl data. Group A subjects exhibited stability of drug levels over time. Fetal heart rate tracings in 21 patients demonstrated no changes associated with epidural opioid infusion in either group. CONCLUSIONS: With the dosage regimen used in this study, an initial epidural bolus with continuous infusion technique generates a steady state plasma concentration of alfentanil that is below levels associated with direct respiratory depression. PMID- 7999652 TI - Evaluation of brachial plexus anesthesia for upper extremity surgery. AB - BACKGROUND AND OBJECTIVES: Brachial plexus anesthesia is the preferred anesthetic at the authors' institution for upper extremity surgery. The article is a prospective observational evaluation of brachial plexus anesthesia for surgical success of the block and immediate and postoperative complications. METHODS: Patients for upper extremity surgery (n = 508) received either an interscalene block (n = 266) or an axillary block (n = 242). Surgical anesthesia was achieved in 97% of the patients receiving an interscalene block and 93% receiving an axillary block. RESULTS: For the interscalene block, a proximal paresthesia (shoulder) was as reliable as a more distal paresthesia (forearm, hand) for shoulder surgery. For performance of the axillary block, the transarterial approach was more successful than a single paresthesia for surgical anesthesia (96% versus 80%). Major immediate complications were infrequent, with only one mild seizure in the axillary block group and evidence of intravascular injection in only two of the patients in the interscalene block group. Many of the patients had mild paresthesias on the first day after the operation, 9% for the interscalene block and 19% for the axillary block. The incidence of postoperative neuropraxias decreased significantly by 2 weeks (interscalene block 3%, axillary block 5%), with only one patient in each group still experiencing symptoms beyond 4 weeks. In the interscalene block group, postoperative neuropraxias were associated with the site of paresthesia used for performance of the block and the use of bupivacaine. CONCLUSION: Both interscalene and axillary blocks are safe and effective techniques for upper extremity surgery. PMID- 7999651 TI - Evaluation of combined spinal-epidural anesthesia using two different techniques. AB - BACKGROUND AND OBJECTIVES: This investigation was designed to evaluate combined spinal-epidural anesthesia with a needle-through-needle technique using two different needle sets. One kit has a standard 16-gauge Tuohy needle and a 26 gauge spinal needle that extends 13 mm beyond the tip of the Tuohy needle (set A). The other kit consists of a 16-gauge Tuohy needle with an aperture in its curve (back hole) for the insertion of a 26-gauge spinal needle that protrudes 10 mm beyond the tip of the epidural needle (set B). METHODS: Combined spinal epidural anesthesia was used in 40 consecutive consenting patients scheduled for elective total knee arthroplasty who were randomized into two groups. Needle set A was used in group A, and needle set B was used in group B. Special attention was paid to difficulties in performing the blocks and to any complications of the technique. RESULTS: The length of the spinal needle was inadequate in 15% of patients from group B, whereas the length in group A was adequate in all. The aperture on the back of the Tuohy needle from group B provides a better "feel" of dural puncture. There was no difficulty in the insertion of the epidural catheter. There was no evidence of subarachnoid placement of the epidural catheter in either group. None of the patients had unexpectedly extensive spinal block. No patient developed postdural puncture headache. All patients had adequate surgical anesthesia. Infusion of bupivacaine (0.1%) with fentanyl (2 micrograms/mL) provided adequate postoperative analgesia. No respiratory depression was noted. CONCLUSIONS: Combined spinal-epidural provides satisfactory surgical and postoperative analgesia for total knee arthroplasty. An improved needle set for the needle-through-needle technique would be one with a modified Tuohy needle having an aperture at the back and a spinal needle protruding more than 13 mm beyond the Tuohy needle. PMID- 7999653 TI - Addition of fentanyl to 1.5% lidocaine does not increase the success of axillary plexus block. AB - BACKGROUND AND OBJECTIVES: This randomized, double-blind study was designed to evaluate the effects of the addition of fentanyl (F) to lidocaine (L) on the onset, duration, and success rate of axillary brachial plexus block. METHODS: After institutional approval and informed consent, 53 ASA 1 and ASA 2 patients scheduled for orthopedic surgery using brachial plexus anesthesia were included in the study. Axillary brachial plexus block was performed using a peripheral nerve stimulator to localize one nerve of the major plexus. The patients were randomly allocated to two groups. The L + F group (n = 27) were administered 38 mL of 1.5% L with 1/200,000 epinephrine and 100 micrograms of F, and the L + S group (n = 26) were administered 38 mL of 1.5% L with 1:200,000 epinephrine and 2 mL of normal saline. The onset (monitored every 5 minutes) and duration (monitored every 30 minutes) of surgical anesthesia, defined as the total abolition of the pinprick response, were evaluated in each nerve territory. RESULTS: The patients were similar with regard to demographic data and the nerve trunks stimulated. In the L + F group, the onset time was only reduced (P = .012) for the musculocutaneous nerve. The duration of surgical anesthesia and the motor block were similar in both groups. The frequency of complete plexus block and the frequency of anesthesia for each nerve trunk were similar in both groups. CONCLUSION: There is no clinical benefit resulting from the addition of fentanyl to the local anesthetic for axillary brachial plexus block. PMID- 7999654 TI - Analysis of heart rate dynamics as a measure of autonomic tone in obstetrical patients undergoing epidural or spinal anesthesia. AB - BACKGROUND AND OBJECTIVES: The purpose of this study is to determine if spectral analysis of beat-to-beat heart rate variability will provide important data on autonomic nervous system function during either spinal or epidural anesthesia that is not apparent from the monitoring of mean heart rate and blood pressure. METHODS: Twelve ASA I patients presenting for elective cesarean delivery (7 epidural and 5 spinal anesthetics) were prospectively selected for study. Control and postblock 10-minute segments of instantaneous heart rates were analyzed for each patient. The total spectral power (Ps, 0.02-0.5 Hz), low frequency spectral power (PLF, 0.02-0.12 Hz), and high frequency spectral power (PHF, 0.12-0.5 Hz) were calculated for each data segment. The complexity of the heart rate time series was estimated by calculating the approximate entropy. RESULTS: Neither spinal or epidural anesthesia had any effect on heart rate or blood pressure. Both spinal and epidural anesthesia did produce a significant decrease in PS, PLF, and PHF. Although there were significant decreases in both the PLF and PHF, there was no change in the PLF/PHF ratio. There was a significant reduction in approximate entropy with spinal and epidural anesthesia, indicating a decrease in complexity of the heart rate dynamics. CONCLUSIONS: These data suggest that autonomic tone decreased with spinal and epidural anesthesia but the sympathetic parasympathetic balance (expressed as PLF/PHF) did not change. Spectral measures, as well as approximate entropy, provide an independent evaluation of the integrity of the autonomic nervous system and cardiovascular control mechanisms that cannot be discerned from mean heart rate and blood pressure. PMID- 7999655 TI - Dilution of proparacaine in balanced salt solution reduces pain of anesthetic instillation in the eye. AB - BACKGROUND AND OBJECTIVES: Proparacaine (P), 0.5%, is often applied topically to the eye to diminish the pain of injection of anesthetic for eye surgery; however, application of 0.5% P itself can cause some degree of discomfort. This study evaluated the use of balanced salt solution to dilute P before instillation in the eye to prevent discomfort. METHODS: In a double-blinded manner, 42 consenting adults about to undergo cataract surgery were given 0.5% P in one eye and 0.03% P in the other eye. One minute later the same solutions were instilled into each eye. Ten minutes later, 0.5% P was instilled into both eyes. After each instillation the patients were asked to describe the pain in each eye on a 0 to 10 scale. RESULTS: Those receiving 0.5% as the first drop had a mean pain score of 1.28, which was greater than the score of 0.09 for the 0.03% P group (P < .01). No one reported pain after the second drop was applied 1 minute later. After receiving 0.5% P 10 minutes later, the group that had received 0.5% P reported a mean pain score of 0.09 while those who had received 0.03% P reported a score of 0.76, which was significantly greater than that reported by the 0.5% P group after the 10 minute instillation (P < .01) but significantly lower than the score reported after the first instillation of 0.5% P (P < .05). CONCLUSIONS: Dilution of P in balanced salt solution to a concentration of 0.03% produces a solution that is significantly less painful than 0.5% P and reduces the discomfort of the instillation of 0.5% P. PMID- 7999656 TI - Effects of combined perioperative epidural bupivacaine and morphine, ibuprofen, and incisional bupivacaine on postoperative pain, pulmonary, and endocrine metabolic function after minilaparotomy cholecystectomy. AB - BACKGROUND AND OBJECTIVES: The study investigates the effects of combined perioperative continuous epidural bupivacaine and morphine, ibuprofen, and incisional bupivacaine, compared with intermittent systemic morphine, ibuprofen, and incisional bupivacaine, on postoperative pain, respiratory function, and endocrine-metabolic alterations associated with minilaparotomy cholecystectomy. METHODS: Thirty-two patients scheduled for cholecystectomy, performed through a minilaparotomy, were randomized to receive general anesthesia with pre- and postoperative thoracic (T7-9) epidural analgesia with bupivacaine and morphine during 38 hours after the operation, or general anesthesia with morphine intramuscular for pain relief every 6-8 hours after the operation. All patients received ibuprofen before the operation until 6 days after the operation, and preoperative infiltration of the surgical field with bupivacaine. RESULTS: Both regimens almost abolished pain at rest, whereas, addition of epidural bupivacaine and morphine significantly improved analgesia during cough and mobilization (P < .05). This improvement was not sustained beyond the expected pharmacologic effect of the epidural analgesics. The postoperative decrease in pulmonary function was only brief and there were no differences between the study groups. No increase in plasma cortisol or glucose was observed from before to 6 hours after the operation, irrespective of the anesthetic regimen. CONCLUSIONS: Epidural analgesia for minilaparatomy cholecystectomy improves pain relief in the immediate postoperative period, compared to intramuscular morphine. Pulmonary and endocrine-metabolic function is not changed to such degree after minicholecystectomy that epidural analgesia can be demonstrated to have beneficial effects. PMID- 7999657 TI - Comparison of patient-assisted epidural analgesia with continuous-infusion epidural analgesia for postoperative patients. AB - BACKGROUND AND OBJECTIVES: Patient-assisted epidural analgesia, a mode of epidural analgesic delivery in which self-administered epidural boluses supplement a baseline continuous epidural infusion, was compared to continuous epidural infusion in 62 postsurgical patients. METHODS: Patients were randomly assigned to receive continuous epidural infusion (n = 31) or patient-assisted epidural analgesia (n = 31) consisting of fentanyl 10 mcg/mL and bupivacaine 1 mg/mL for the first 2 days after the operation. Variables examined included the adequacy of analgesia, amount of epidural infusion solution used, use of supplemental opioids, as well as incidence of side effects including nausea, pruritus, sedation, urinary retention, and respiratory depression. RESULTS: Visual analog pain scores on days 1 and 2 after the operation, mean total epidural fentanyl consumption, and use of supplemental opioids were all significantly (P < .05) lower in the patient-assisted epidural group than in the continuous infusion group. There was no significant difference in the incidence of side effects between groups. The effects of age and operation type were not significant. CONCLUSIONS: Patient-assisted epidural analgesia can provide superior pain control as compared to continuous epidural infusions while also reducing opioid dosages. Despite the reduction in total analgesic administered no reduction in side effects was seen with this mode of administration. PMID- 7999658 TI - Deafferentation pain exacerbated by subarachnoid lidocaine and relieved by subarachnoid morphine. Case report. AB - BACKGROUND AND OBJECTIVES: Neuropathic pain syndromes are often resistant to traditional pharmacologic treatment. The authors describe a patient with chronic deafferentation pain of the legs associated with peripheral neuropathy that was refractory to multidisciplinary pain clinic management. METHODS: Numerous medications had been tried, including nortriptyline, mexiletine, and oral and parenteral opioids. Spinal cord stimulation was also ineffective, despite a satisfactory pattern of stimulation-induced paresthesias. For diagnostic purposes, differential spinal anesthesia with lidocaine and morphine was performed, with evoked potential monitoring used to evaluate the intensity of spinal anesthetic block. RESULTS: Paradoxically, lidocaine spinal anesthesia exacerbated pain, whereas subarachnoid morphine provided rapid pain relief. Long term pain control has been maintained with an implanted spinal infusion pump. CONCLUSIONS: Evoked potential data acquired during lidocaine spinal anesthesia and the rapid pain relief provided by subarachnoid morphine suggest that deafferentation pain may involve segmental, opioid-sensitive dorsal horn pain generators. The long-term pain relief afforded the patient demonstrates that subarachnoid opioids may be efficacious for some forms of neuropathic pain. PMID- 7999659 TI - False positive glucose test following aspiration of bicarbonate-containing local anesthetic solution injected into the epidural space. PMID- 7999660 TI - Further evidence of central (supraspinal) mediation in phantom limb pain. PMID- 7999662 TI - Metallic particles in the spinal-epidural needle technique. PMID- 7999661 TI - Dribble drivel. PMID- 7999663 TI - Thoracic paravertebral block in chronic postoperative pain. PMID- 7999665 TI - Proceedings of the Tokyo symposium on new frontiers in hair research. 25-26 October 1993. PMID- 7999664 TI - The timing of opioid administration in postdural puncture headache. PMID- 7999666 TI - Three-dimensional microvasculature of the hair follicle. AB - The three-dimensional microvasculature of the hair follicle of the adult Wistar rat was demonstrated by scanning electron microscopy of vascular corrosion casts. The anagen hair follicle was surrounded by the basket-like capillary network which was supplied by the branches of the subcutaneous artery and drained into the veins continuous with the subcutaneous vein. The capillary network surrounding the anagen hair follicle was most dense at its bottom, and became sparse at its upper part. The telogen hair follicle was surrounded by only a few capillaries. Transmission electron microscopy showed that the capillaries around the hair bulb possessed fenestrations. Our results indicate that the microvasculature of the anagen hair follicle is so organised as to supply the hair bulb with abundant blood, which is the most important area for hair growth. PMID- 7999667 TI - Effect of minoxidil sulfate and pinacidil on single potassium channel current in cultured human outer root sheath cells and dermal papilla cells. AB - Minoxidil sulfate and pinacidil are K channel openers and are considered to promote hair growth. However, there have been no studies on the single channel current of isolated cells from hair follicles. Therefore, we characterized the single K channel current of outer root sheath cells and dermal papilla cells and the effect of K channel openers on K currents by patch clamp. We also carried out 86Rb efflux studies to observe macroscopic K channel currents. In physiological saline, these two cells showed two types of K channels, large and small conductance Ca(2+)-activated K channels, both intact cell-attached and excised inside-out patches. In symmetrical 150 mM K solution, unitary conductances were 246 and 70 pS, respectively. Intracellular ATP (up to 5 mM) or glibenclamide (20 nM), a specific ATP-sensitive K channel blocker, did not block these channels. Minoxidil sulfate (5 micrograms/ml) or pinacidil (10 microM) did not open these two types of K channels or increase 86Rb efflux. These results suggest that minoxidil sulfate or pinacidil did not activate K channel current in hair follicles, and that the drug effect on hair growth might be mediated by other mechanisms such as increased blood flow. PMID- 7999668 TI - Molecules of the cycling hair follicle--a tabulated review. AB - In this review we tabulated molecules which have been experimentally identified to be associated with, or play a role in, hair follicle growth. While compiling these data we were impressed by the fact that this field is only now beginning to be developed in terms of molecular analysis. Ironically, hair was used in some of the earliest molecular approaches to biologic structure (e.g. Astbury and Street, 1931), but the field did not develop from there. From our review we have come to the following conclusions. (1) As indicated by the growing number of reports dealing with follicle-associated molecules in the past 3 years, the field of hair biology has entered a new molecular era. (2) In many reported hair biology studies not enough emphasis has been placed on the fact that the follicle is a dynamic structure. All too often a study is limited to follicles of one particular phase of the cycle or one phase of development. Students in the field have to be more sensitive to the remarkable changes that this deceptively simple structure can undergo during its cycle. (3) Although we have not been able to find any molecules unique to the follicle, some of the structural molecules come close to an ideal tool. It is our impression that even more specific molecule tags will be found. Whether this requires a subtraction library approach or gene mapping of specific mutants is not yet clear. It would appear that the large, diverse family of intermediate filament-associated proteins will prove to be an excellent source of unique follicle-labeling molecules. (4) There is an acute need for molecules which distinguish the phases of the cycle, e.g. telogen from early anagen. Telogen is by far the most difficult phase to identify morphologically since the earliest phase of anagen and the latest phase of catagen may appear structurally like telogen. That these phases are functionally distinguishable must imply a molecular difference. As the number of recognized hair follicle-associated molecules and their interactions increase, it will be essential to assemble libraries of highly specific RNA and antibody probes for localization and mapping studies. We recognize that this review, as written, is imperfect. It is particularly deficient in making any effort towards identifying unifying principles of structure and function. We look forward to returning to this subject within 3 years.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 7999669 TI - The aetiology and pathogenesis of alopecia areata. AB - In common with a number of inflammatory autoimmune diseases, genetic factors including HLA class II associations have been identified in alopecia areata. No consensus has been reached on the identity of a specific disease target within the hair follicle in alopecia areata. Suggested candidate cell types include the dermal papilla cells, the keratinocytes of the matrix and presumptive cortex and the hair bulb melanocytes, but these need not be mutually exclusive. The pathogenesis is known to involve disturbance of immune function but there is no proof that an autoimmune mechanism is fundamental. We propose a pathogenetic model incorporating polygenic determination of disease susceptibility and severity with additional, possibly environmental, factors as triggers for disease expression. PMID- 7999670 TI - Two- and three-dimensional observations of human terminal and vellus hair follicles. AB - Extracted human terminal and vellus hair follicles were prepared by EDTA and examined by light and electron microscopes. These samples were morphologically well preserved and enabled us to observe 3-dimensional (3-D) views of the outer surfaces of hair follicles. Interestingly, the bulge areas of terminal and vellus hair follicles showed several morphological variations, such as knob-like swellings and villous projections, independent of hair cycle. Moreover, skirt like structures were furnished in the small vellus hair follicles independent of hair cycle, but not terminal and large vellus hair follicles. These morphological variations of human hair follicles were confirmed to genuinely represent 3-D views by means of the conventional transverse and vertical sections of the human skin. PMID- 7999671 TI - Quantitative evaluations of male pattern baldness. AB - Several methods for the evaluation of hair growth have been reported; however, none of the hitherto reported methods are satisfactory as unbiased double blind studies to evaluate the efficacy of hair growth agents. In the present paper, we describe quantitative evaluation methods for hair growth by measuring the anagen ratio and hair diameters in 56 Japanese subjects aged 23-56 for 3 years. The average anagen ratio decreased by 3.8% in 3 years. The average hair diameters showed a statistically significant decrease each year totalling 3.4 microns. Subjects were sorted according to their anagen ratio into 4 groups. Each group showed different distribution patterns of hair diameters. The higher anagen ratio group has a high frequency peak at thicker hair diameters and the lower anagen ratio group has a high frequency peak at thinner hair diameters. The number of thicker hairs decreased and the high frequency peak shifted to thinner hair diameters in 3 years. These methods are useful to evaluate both the progression of male pattern baldness and the effects of hair growth agents with double blind studies in an unbiased quantitative fashion. PMID- 7999672 TI - Modulation of the differentiated phenotype of keratinocytes of the hair follicle and from epidermis. AB - The differentiation capacity and its modulation by cell-cell and cell-matrix interactions of epithelial cells from epidermis (NEK), hair follicle outer root sheath (ORS) and hair matrix cells (HMC) in different experimental model systems is reviewed. Reformation of structurally intact and functioning hair follicles has been achieved with isolated neonatal mouse cells in vivo when follicular epithelia and dermal fibroblasts were transplanted. This structural reorganization has not yet been feasible in vitro in either surface or matrix embedded organotypic cocultures with mesenchymal cells. While the epithelial cells isolated from epidermis or hair follicle compartments formed similar stratified and keratinizing epithelia in vitro, their degree of differentiation was significantly different, declining from NEK over ORS to HMC. Differentiation was further reduced in HMC cultures in the presence of dermal papilla cells (DPC). Differentiation was analyzed by morphologic criteria and the biochemical analysis as well as immunohistochemical localization of differentiation products such as keratins, involucrin, filaggrin, integrins, basement membrane components and membrane antigens. The results demonstrate fully maintained differentiation capacity of skin and appendage-keratinocytes to reconstitute a squamous epithelium, reflecting their common origin from embryonic epidermis. For the induction of hair follicle-specific structural and functional characteristics, different and probably more complex interactive mechanisms may be required. PMID- 7999673 TI - Common transglutaminase substrates shared by hair, epidermis and nail and their function. AB - The hair follicle contains several components with different programs of differentiation some of which include the synthesis of a cornified envelope. Our interest in cornified envelope precursors of the epidermis prompted an investigation of the location of several of these in the hair follicle. Monoclonal antibodies to the precursor proteins involucrin, pancornulin and sciellin were reacted with frozen section of skin and their localization detected by fluorescein tagged antibodies or the peroxidase technique. Staining was observed in the ostium and isthmus of the hair follicle using all 3 antibodies and was similar to that observed in epidermis. Staining of the inner root sheath was also observed with all 3 antibodies. In the case of the antibody to sciellin, the reaction was clearly localized to the cell periphery using special fixation. The other antibodies did not react by this technique and appeared to show cytoplasmic staining. Similar studies with nail also showed reactivity, but the distribution of the 3 proteins in the different regions of the nail varied. The role of the envelope precursors in the hair follicle remains to be established. The inner root sheath does not appear to have a fully developed cornified envelopes and isopeptide bond formation occurs primarily in the cytoplasm. These proteins may have a role similar to trichohyalin in cornification of the inner root sheath. PMID- 7999674 TI - Normalization of hair growth in sparse fur-abnormal skin and hair (SPF-ASH) mice by introduction of the rat ornithine transcarbamylase (OTC) gene. AB - The sparse fur-abnormal skin and hair (SPF-ASH) mouse is a model for the human X linked hereditary disease, ornithine transcarbamylase (OTC) deficiency. This condition is characterized by abnormal skin and delayed hair growth, hyperammonemia, orotic aciduria and low levels of serum citrulline and arginine. Murakami et al. [1] established a line of transgenic mice, by introducing the recombinant rat OTC (rOTC) gene into fertilized C57BL mouse eggs. We introduced the rOTC gene into SPF-ASH mice by mating SPF-ASH heterozygotes and transgenic mice, which carried this gene. The hemizygous SPF-ASH mice bearing the rOTC gene showed normal hair growth without sparse fur, normal urinary orotic acid excretion and normal serum citrulline and arginine levels. These mice showed OTC activities 2 and 6 times higher in the liver and small intestine, respectively, than the SPF-ASH mice but about 12% and 27% those of the controls [2]. PMID- 7999675 TI - Effect of cyclosporin on hair-existing area of nude mice. AB - We investigated the effect of cyclosporin, as well as minoxidil, testosterone, estradiol and corticosteroid on the hair growth on the hairy part of nude mice. Aliquots of solutions of cyclosporin and other agents were applied once per every day topically on the tails and the lower backs of 5 week-old BALB/c nude mice, for as long as 6 weeks. Cyclosporin prolonged the hair-existing phase of the hair cycle, but did not change the term of the hair cycle, i.e., the resting phase was not affected. Minoxidil, testosterone and estradiol did not influence the hair growth cycle. Combination of cyclosporin and other agents demonstrated that there was neither additive nor synergistic effect, but a high dose of corticosteroid inhibit the cyclosporin effect, as well as suppressing completely the reappearance of the growing phase. PMID- 7999676 TI - Human hair growth in vitro: a model for the study of hair follicle biology. AB - The factors that regulate hair follicle growth are still poorly understood. In vitro models may be useful in elucidating some aspects of hair follicle biology. We have developed an in vitro human hair growth model that enables us to maintain isolated human hair follicles for up to 10 days, during which time they continue to grow at an in vivo rate producing a keratinised hair fibre. We have shown that epidermal growth factor (EGF) in our system mimics the in vivo depilatory action of EGF in sheep, and suggest that this occurs as a result of EGF stimulating outer root sheath (ORS) cell proliferation which results in the disruption of normal mechanisms of cell-cell interaction in the hair follicle. We identify transforming growth factor-beta (TGF-beta) as a possible negative regulator of hair follicle growth and show that physiological levels of insulin-like growth factor-I (IGF-I) can support the same rates of hair follicle growth as supraphysiological levels of insulin. Furthermore, in the absence of insulin hair follicles show premature entry into a catagen-like state. This is prevented by physiological levels of IGF-I. Finally we demonstrate that the hair follicle is an aerobic glycolytic, glutaminolytic tissue and discuss the possible implications of this metabolism. PMID- 7999677 TI - The effect of various cytokines on hair growth of mouse vibrissae in organ culture. AB - Hepatocyte growth factor/scatter factor (HGF) is a multifunctional polypeptide which acts as a mitogen, motogen or morphogen depending on the biological context. In this study, we examined the effect of HGF on hair growth using a serum-free organ culture system. Vibrissal hair follicles isolated from newborn mice were cultured at 31 degrees C in 95% O2-5%CO2 for 72 h in the presence of various cytokines or growth factors. DNA, protein synthesis and elongation of the hair shaft in the hair follicles were measured. Among the agents tested, only HGF significantly increased hair follicle length (P < 0.001) and 3H-thymidine (P < 0.001) incorporation. The effect of HGF was dose-dependent, with maximal stimulation obtained at 10 ng/ml. The increase in hair follicle length and thymidine incorporation were specifically inhibited by a neutralizing antibody against HGF. These results indicate that HGF is able to promote hair growth and may have clinical utility in this regard. PMID- 7999678 TI - Dermal papilla cells express hepatocyte growth factor. AB - In the induction, development and maintenance of hair follicles, it is thought that an epithelial-mesenchymal interaction is important and that the dermal papilla plays some important roles. Hepatocyte growth factor is a multifunctional polypeptide which acts as mitogen, motogen or morphogen depending on the biological context. Recently, we found that HGF stimulates hair follicle growth in a mouse organ culture system, and therefore proceeded to investigate the expression of HGF on cultured human dermal papilla cells (DPC) and the effect of HGF on cultured human keratinocytes derived from hair bulb. Using an enzyme immuno assay, HGF immunoreactivities were not detected in conditioned media of DPC that were either non-treated or treated with TGF-beta, but were detected in conditioned media of DPC treated with IL1-alpha, TNF-alpha and TPA. Using the reverse transcription-polymerase chain reaction (RT-PCR) method, HGF mRNA was also detected in DPC. This expression was enhanced by IL1-alpha, TNF-alpha and TPA, but suppressed by TGF-beta. Furthermore, HGF stimulated the DNA synthesis in keratinocytes derived from human hair bulb in a dose-dependent manner. These results indicate that DPC express HGF in vitro and that HGF stimulates the growth of human keratinocytes derived from hair bulb in vitro. PMID- 7999679 TI - Hair follicle reconstruction in vitro. AB - The in vitro creation of a follicular structure capable of hair growth from cultured adult cells has long been an aim of researchers in hair biology. Basal outer root sheath cells (ORS) attached to the hair follicle glassy membrane (GM) were isolated and cultured, where they revealed greater replicative potential and longevity than ORS cells from plucked fibres. Hair follicles were reconstructed in vitro using the collagenous shells of rat vibrissa follicles as natural containers for 4 hair follicle cell types. Basal ORS cells were initially seeded onto the residual vibrissa GM, and cultured dermal papilla, dermal sheath and germinative epidermal cells were then added. Histology revealed that after 2 or 3 weeks in combined culture, cell interactions and tissue morphogenesis had resulted in the formation of irregular but recognizable hair fibres, produced from unusual bulb structures. To our knowledge this represents the first example of adult cell populations instigating the de novo creation of hair fibres in a culture dish. While the usefulness of the current methodology relates immediately to hair growth research, the generation of hair follicles and fibres in vitro establishes the enormous potential of this type of interactive work for practical purposes. PMID- 7999680 TI - Mechanism of action of androgen in hair follicles. AB - In order to investigate the mode of action of testosterone (T) on human hair follicles we studied the metabolism of T and localization of androgen receptors in outer root sheath cells (ORSC) and dermal papilla cells (DPC) from different body sites. T was principally metabolized to androstenedione (delta 4) even in beard ORSC as well as epidermal keratinocytes (EK), and the ratio of apparent 5 alpha-reductase (5 alpha-R) to 17 beta-hydroxysteroid dehydrogenase (17 beta-HSD) did not differ between these two kinds of cells. The 5 alpha-R activity in beard DPC was 3 times as high as that in occipital scalp and axillary DPC. The 5 alpha R of beard DPC exhibited a narrow optimum pH of 5.5, which is characteristic of type 2 enzyme present in androgen target cells. In contrast, 5 alpha-R of DPC from axillary and occipital scalp hair showed a broad optimum pH range between 6.5-9.0 corresponding to type 1 5 alpha-R. Androgen receptors were detected in the DPC of beard and axillary hair follicles, but not in those of occipital scalp hair follicles using immunohistochemical staining with polyclonal anti-androgen receptor antibody. Epithelial cells of the hair bulb were not stained by the antibody. Androgen receptors were also detected in the nuclei of cultured beard and axillary DPC, but the DPC from occipital scalp hair follicles showed little staining with the antibody. We also examined the effects of T on the DNA synthesis and proliferation of cultured ORSC and DPC. T did not have a proliferative effect on either type of cell when cultured alone.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7999681 TI - A classical dilemma. PMID- 7999682 TI - Pregnancy-associated osteoporosis. PMID- 7999683 TI - Mobile regional analgesia in labour. PMID- 7999684 TI - Practical assessment of neonatal nutrition status beyond birthweight: an imperative for the 1990s. PMID- 7999685 TI - Misuse of lasers in gynaecology. PMID- 7999686 TI - Variation in obstetric care within and between hospital levels in Finland. AB - OBJECTIVE: In obstetrics, both area and hospital variation has previously been documented for operative procedures, but not for other treatments or diagnostic procedures. This study investigated the extent of variation in care during pregnancy, at birth and after birth. DESIGN AND METHODS: The variation was studied by hospitals (n = 52) by hospital level. To account for differences in women's background characteristics, logistic regression analyses were done. The data came from the 1991 Finnish Birth Register which records data on all births (n = 64,171). RESULTS: All interventions and care practices studied varied notably from one hospital to another, with the variation usually being greater within hospitals of the same level than between hospitals of different levels. Each of the seven non-operative interventions showed a larger variation than did each of the four operative interventions. Standardisation for mothers' background characteristics did not eliminate this variation. Some interventions, but not all, were clustered in the same hospitals. CONCLUSIONS: Such large variation indicates a need for further studies on the benefits of obstetric interventions and of care practices, and on better application of research results to obstetric care. PMID- 7999687 TI - Employment during pregnancy in relation to risk factors and pregnancy outcome. AB - OBJECTIVE: To describe the relation of employment status during pregnancy to potential demographic, behavioural and obstetrical risk factors for adverse late pregnancy outcome, as well as the risks of having a preterm delivery and a small for gestational age infant. DESIGN: Cohort study. SETTING: A university hospital. SUBJECTS: Of 8,711 women with singleton pregnancies (1989-91), 5,875 returned questionnaires about risk factors and employment status at 16 and 30 weeks gestation. Of the respondents 5,552 were analysed in five groups: (1) women working throughout pregnancy, (2) women working in the first, but unemployed during the second trimester, (3) women on sick leave in the first and second trimester, (4) women unemployed throughout pregnancy, and (5) students. The association between employment status and having a small for gestational age infant and preterm delivery was evaluated, accounting for other risk factors. RESULTS: Working women and students had the most and unemployed women the least favourable demographic risk factors. Women on sick leave had the least favourable obstetrical and medical history, followed by unemployed women. No clear pattern of the behavioural risk factors was found. Differences in risk of having a small for gestational age infant were a function of parity, smoking and maternal height. Adjustment for these factors plus education yielded a lower risk of preterm delivery in partially unemployed women and higher risk among women on sick leave compared to working women, accounted for by different risks of bleeding in the second and third trimester. CONCLUSIONS: Comparison of pregnancy outcome among women with different work status should consider the differences in risk factor profile. Adjusting for such risk factors, we found no evidence that work per se had any detrimental or beneficial effects on the risk of having a small for gestational age infant or preterm delivery. PMID- 7999688 TI - Antenatal fetal magnetocardiography: a new method for fetal surveillance? AB - OBJECTIVE: To establish the reliability of fetal magnetocardiography as a method of measuring the time intervals of the fetal heart during the antenatal period. DESIGN: A prospective study. SETTING: Wellcome Biomagnetism Unit, Southern General Hospital. SUBJECTS: One hundred and six low risk pregnant women at 20 to 42 weeks gestation. MAIN OUTCOME MEASURES: Success in obtaining QRS complexes, P waves and T waves. Correlation of time intervals with fetal outcome. RESULTS: The technique was acceptable to pregnant women. A QRS complex was successfully demonstrated in 68 (67%) of the unaveraged traces. Using off-line averaging techniques on these 68 cases, P waves were obtained in 75% and T waves in 72%. Although good quality traces were obtained throughout the range of gestational ages, in general it was more difficult below 28 weeks. QRS duration (R2 = 7%, P = 0.02) demonstrated a positive linear correlation with increasing gestation. Of the 35 (51%) cases with umbilical vein pH analysis available, only one result was less than 7.2. No significant relation was found between measurements of the fetal waveforms and the pH results. CONCLUSION: The technique of fetal magnetocardiography provides a significant advance in the technological field for the demonstration of QRS complexes and the full PQRST waveforms in gestations from 20 weeks onwards. With further technical improvements the clinical impact of this technique can be assessed more fully. PMID- 7999690 TI - A survey of views on hormone replacement therapy. AB - OBJECTIVE: To investigate the attitude of consultant gynaecologists and general practitioners to various aspects of hormone replacement therapy and to compare the findings in these two groups. DESIGN: Anonymous postal survey of 589 general practitioners and 998 consultant gynaecologists; 373 (63%) and 655 (66%) valid replies, respectively, were received. MAIN OUTCOME MEASURES: Views on universal treatment of eligible women, indications for hormone replacement therapy, prescribing practice, pretreatment investigation, monitoring, and contraindications to treatment. RESULTS: More consultants (64%) than general practitioners (56%) thought hormone replacement therapy should be offered to all eligible women, with a significant trend against treatment amongst more senior consultants. Most practitioners were prepared to offer treatment before the cessation of menstruation, but only 27% of consultants and 11% of general practitioners recommended indefinite treatment. Most limited treatment to less than 10 years. Menopausal symptoms, premature natural and surgical menopause, and a family history of osteoporosis were regarded as indications for treatment, but less than half felt established osteoporosis an indication. Hormone replacement therapy was judged to reduce the risk of ischaemic heart disease and osteoporosis by both groups but there was less consensus on the prevention of cerebrovascular accident. In general, consultants had more faith in hormone replacement therapy as prophylaxis. One-quarter of consultants said that hormone replacement therapy should be initiated by consultants. Only 4% of general practitioners shared this view. About 30% of both groups required mammography, but less than 10% required sophisticated tests. A range of common cardiovascular conditions were regarded as contraindications, although general practitioners were more likely to regard thrombosis and cerebrovascular accident as contraindications. Breast cancer and a family history of breast cancer were regarded with suspicion by both groups. CONCLUSIONS: Practitioners were positively inclined to hormone replacement therapy, but many were unconvinced of its chronic use and use in those with cardiovascular conditions. There were differences in views as to who should initiate therapy. PMID- 7999689 TI - The effects of dihydralazine, labetalol and magnesium sulphate on the isolated, perfused human placental cotyledon. AB - OBJECTIVE: To assess the effects of dihydralazine, labetalol and magnesium sulphate on the vascular tone in the isolated, perfused human placental cotyledon. METHODS: In vitro perfusion of the fetal compartment of isolated, human placental cotyledons. RESULTS: None of the drugs affected basal vascular tone. The thromboxane A2-mimic U46619 and endothelin-1 induced a concentration dependent increment in perfusion pressure, while 5-hydroxytryptamine induced a variable increase, and norepinephrine induced a small, transient increase in perfusion pressure. After preconstriction with U46619, magnesium sulphate (1.5 x 10(-3) to 6 x 10(-3) mol/l) induced a decrease in perfusion pressure, while dihydralazine (10(-6) to 10(-4) mol/l) or labetalol (10(-7) to 10(-4) mol/l) enhanced the perfusion pressure. These effects of dihydralazine and labetalol were unaffected by treatment with indomethacin 10(-6) mol/l, but could be reversed by addition of magnesium sulphate 6 x 10(-3) mol/l. Labetalol 10(-6) to 10(-4) mol/l also caused an increase in the perfusion pressure induced by endothelin-1, but showed no effects after preconstriction with 5 hydroxytryptamine. Pretreatment with labetalol 10(-4) mol/l inhibited the transient increase in perfusion pressure induced by norepinephrine 3 x 10(-5) mol/l. CONCLUSIONS: The present data demonstrated that the commonly used vasodilating agents labetalol and dihydralazine do not produce vasodilatation in the human perfused cotyledon after vasoconstriction induced by agents of suggested importance for maintenance of fetal placental vascular tone, and that high concentrations of these drugs may even enhance vasoconstriction induced by thromboxane and endothelin-1 in this area. Magnesium sulphate may show the potential to reverse such unwanted effects of dihydralazine and labetalol. PMID- 7999691 TI - Serum albumin and CA125 are powerful predictors of survival in epithelial ovarian cancer. AB - OBJECTIVE: To assess the prognostic significance of presentation serum albumin, clinical stage and CA125 levels in ovarian cancer. DESIGN: Retrospective analysis of data using a Cox proportional hazards model. SETTING: A district general hospital oncology unit. SUBJECTS: One hundred and fourteen consecutive patients with epithelial ovarian cancer. INTERVENTIONS: Cytotoxic chemotherapy and surgery. MAIN OUTCOME MEASURE: Survival. RESULTS: A linear increase in risk was observed with high log CA125 (P < 0.0001) and with low albumin (P < 0.0001). In late stage patients (III and IV) albumin is the best predictor of survival (P = 0.0006). The presence of ascites, blood transfusion, type of surgery or chemotherapy did not improve the predictive model. CONCLUSIONS: CA125 and albumin can be used to identify prognostic subgroups independently of stage. Albumin alone can also be used as a predictor of survival. A simple classification of patients into three groups based on serum albumin of 41 g/l or more, 35 to 40 g/l and 34 g/l or less provides a clear separation of survival curves in the present group of patients. PMID- 7999692 TI - Roles of prostaglandins and intracellular free calcium mobilisation in epidermal growth factor-induced proliferation of human amnion cells. AB - OBJECTIVE: To investigate the mechanisms which regulate the growth of human amnion cells. DESIGN: A prospective descriptive study. SUBJECTS: Women undergoing caesarean section at term before the onset of labour. INTERVENTIONS: Amnion cells were cultured in monolayer. MAIN OUTCOME MEASURES: Cell cycle analysis, intracellular calcium levels, prostaglandin (PG) production rates. RESULTS: Epidermal growth factor (EGF) stimulated intracellular Ca2+ mobilisation and PGE2 production in cultured amnion cells. The addition of a Ca2+ channel blocker (cobalt) or a Ca2+ chelator (EGTA) into the culture medium inhibited intracellular Ca2+ mobilisation and PGE2 production induced by EGF. The analysis of cell cycles showed that EGF induced the initiation of DNA synthesis and that the addition of cobalt or EGTA into the culture medium inhibited EGF-induced DNA synthesis. The addition of a cyclo-oxygenase inhibitor (indomethacin) inhibited PGE2 production and DNA synthesis induced by EGF without the effect on intracellular Ca2+ mobilisation. Moreover, the inhibitory effect of indomethacin on EGF-induced DNA synthesis was attenuated by the addition of exogenous PGE2 or PGF2 alpha. CONCLUSIONS: These data suggest that EGF induces an increase in intracellular Ca2+ levels and the rate of prostaglandin production which leads to proliferation of human amnion cells. PMID- 7999693 TI - Laparoscopic pelvic lymphadenectomy versus traditional surgery in pigs. PMID- 7999694 TI - Laparoscopic versus conventional pelvic lymphadenectomy for gynaecological malignancy in humans. PMID- 7999695 TI - Small fetal transverse cerebellar diameter: a screening test for spina bifida. PMID- 7999696 TI - Maternal mortality in Hong Kong 1986-1990. PMID- 7999697 TI - Embolisation of massive bleeding following hysterectomy, despite internal iliac artery ligation. PMID- 7999698 TI - Severe factor X deficiency and successful pregnancy. PMID- 7999699 TI - Fetomaternal haemorrhage treated with intravascular transfusion: a late complication of amniocentesis? PMID- 7999700 TI - Charts of fetal size. PMID- 7999701 TI - Charts of fetal size. PMID- 7999702 TI - Charts of fetal size. PMID- 7999703 TI - Ovarian biopsy for diagnosis of premature menopause. PMID- 7999704 TI - Ovarian biopsy for diagnosis of premature menopause. PMID- 7999705 TI - Postpartum eclampsia associated with ergometrine maleate administration. PMID- 7999706 TI - Validation of automated blood pressure recording in pregnancy. PMID- 7999707 TI - Cigarette smoking on histological outcome in women with mildly dyskaryotic cervical smears. PMID- 7999708 TI - Fetal heart rate variability prior to delivery in women with severe hypertension who developed placental abruption. PMID- 7999709 TI - Reconstruction of the mons pubis with a myocutaneous island flap of the rectus abdominis muscle. PMID- 7999710 TI - Maternal platelet angiotensin II binding and fetal Doppler umbilical artery flow waveforms. PMID- 7999711 TI - Antenatal fetal therapy for neonatal allo-immune thrombocytopenia with high dose immunoglobulin. PMID- 7999713 TI - Refractory gestational hypertension due to a renin-secreting ovarian fibrothecoma associated with Gorlin's syndrome. PMID- 7999714 TI - Successful use of Sengstaken-Blakemore tube to control massive postpartum haemorrhage. PMID- 7999712 TI - Corticosteroids for the treatment of hyperemesis gravidarum. PMID- 7999715 TI - Spontaneous uterine rupture during subsequent pregnancy following non-excision of an interstitial ectopic gestation. PMID- 7999716 TI - Length of stay after vaginal hysterectomy. PMID- 7999717 TI - Working towards a European strategy for interventions to reduce vertical transmission of HIV. PMID- 7999718 TI - Increased maternal serum free beta human chorionic gonadotrophin concentrations in Down's pregnancies: an artefactual finding? PMID- 7999719 TI - Wound recurrence by implantation of a borderline ovarian tumour following laparoscopic removal. PMID- 7999720 TI - Chaos theory in obstetrics and gynaecology. PMID- 7999721 TI - Oophorectomy at the same time as hysterectomy. PMID- 7999722 TI - The role of caesarean section in the delivery of the very preterm infant. PMID- 7999724 TI - The origin and inception of the Confidential Enquiry into maternal deaths. PMID- 7999723 TI - The role of ultrasound and tumour markers in the early detection of ovarian cancer. PMID- 7999725 TI - Factors potentiating the smoking-related risk of fetal growth retardation. AB - OBJECTIVE: To estimate the risk of fetal growth retardation resulting from the interaction between maternal smoking during pregnancy and other recognized risk factors. DESIGN: Case-control study of prospectively recorded data. SETTING: Department of Obstetrics and Gynaecology, University of Pavia, Italy. SUBJECTS: Three hundred and forty-seven singleton pregnancies with diagnosis of fetal growth retardation and 694 control pregnancies with appropriately grown fetuses. RESULTS: The overall odds ratio for fetal growth retardation associated with maternal smoking was 2.87 (95% confidence interval, 2.17-3.80). In logistic models the factors which independently increased the smoking-related risk of fetal growth retardation were a male fetus, nulliparity, maternal age 20 years or less, a history of first trimester haemorrhage and low (less than 50 kg) pre pregnancy weight. The combined effect of smoking and caffeine consumption on the risk of fetal growth retardation was found to be additive rather than multiplicative. CONCLUSIONS: Several factors can affect the risk of fetal growth retardation associated with maternal smoking. The prenatal identification of these factors could help detect subgroups of women at high risk of fetal growth retardation. PMID- 7999726 TI - Evaluation of an antenatal HIV testing programme in an inner London health district. AB - OBJECTIVE: To study an antenatal human immunodeficiency virus (HIV) testing programme in an inner London health district. DESIGN: A standardised research interview was given to women in the first half of pregnancy and the findings were compared with those of the routine clinical interview. The observations were analysed in relation to the results of HIV antibody testing, either attributable by consent or anonymously, in these women. SETTING: The Homerton Hospital, London. SUBJECTS: Three thousand seven hundred and twenty-nine women, of whom 1696 (45.5%) consented to testing. RESULTS: Four women who had consented to testing had a positive result. Amongst the 2,033 women (54.5%) who declined the test, four (or five) had a positive result. The number of risk factors ascertained by the research study interview was substantially greater than that elicited by the preceding routine interview. In addition, more information was obtained by a routine computer interview than by its unstructured equivalent. There was no obvious association between the presence of a risk factor and whether or not the women had consented to the test. CONCLUSIONS: Our formal voluntary testing programme detected nearly 44% of HIV seropositive individuals. Thus, there were four known positives during the study period against a total of nine detected by anonymous testing. Since all the known positive results in the study were associated with recognised risk factors, there is some doubt as to the value of a universal testing programme. However, if testing is to be based upon the existence of a risk factor elicited at the booking history, then the deficiencies in this history revealed by the present study need to be corrected. PMID- 7999727 TI - Chorionic villous haemorrhage is associated with retroplacental haemorrhage. AB - OBJECTIVE: To examine the frequency of occurrence of chorionic villous haemorrhage in placentas with retroplacental haemorrhage, and to discuss the pathogenesis of these conditions. DESIGN: A retrospective study using histological sections of formalin-fixed, paraffin-embedded placental tissue stained with haematoxylin and eosin. SETTING: Department of Histopathology, Rotunda Hospital, Dublin. SUBJECTS: Sixty cases of retroplacental haemorrhage, 34 cases of chorioamnionitis, and 24 histologically normal placentas. MAIN OUTCOME MEASUREMENT: Presence or absence of chorionic villous haemorrhage. RESULTS: Chorionic villous haemorrhage was present in 31 of 60 cases of retroplacental haemorrhage (51%), one of 34 cases of chorioamnionitis (2.9%) and in no normal placentas. CONCLUSIONS: It is postulated that chorionic villous haemorrhage reflects a disturbance of fetal vascular dynamics and precedes retroplacental haemorrhage. Such a disturbance could trigger the events leading to abruption. PMID- 7999728 TI - Behavioural state dependency of renal artery and descending aorta velocimetry and micturition in the normal term fetus. AB - OBJECTIVE: To examine the behavioural state dependency of renal artery and descending aorta pulsatility index and hourly fetal urinary production rate (HFUPR) in the normal term fetus. DESIGN: An observational study. SUBJECTS: Twenty-three healthy women with a normal singleton pregnancy between 36 and 40 weeks gestation. MAIN OUTCOME MEASURES: Renal artery and descending aorta pulsatility indices were established using pulsed Doppler ultrasound. HFUPR (ml) was estimated using real-time ultrasound. Fetal behavioural states 1F (quiet sleep) and 2F (active sleep) were determined from combined recordings of fetal heart rate, eye movements and body movements. RESULTS: An inverse correlation between pulsatility index and fetal heart pattern was established for both the renal artery (r = 0.60; SD = 0.22; P = 0.0001) and the descending aorta (r = 0.73; SD = 0.16; P = 0.0001). The difference in mean pulsatility index between states 1F and 2F adjusted for fetal heart pattern was 0.09 (SD 0.23) for the renal artery (P = 0.02) and 0.26 (SD 0.19) for the descending aorta (P = 0.0001). Mean HFUPR was significantly higher (44.8%, P = 0.01) in state 1F (96 ml) compared with state 2F (54 ml). During the urinary filling phase, a poor correlation existed between renal artery pulsatility index and HFUPR (r = 0.04) and between descending aorta pulsatility index and HFUPR (r = 0.01). CONCLUSIONS: In the normal term fetus renal artery and descending aorta pulsatility indices are reduced during fetal behavioural state 2F, suggesting reduced downstream impedance at the fetal trunk and in particular at renal level. This behavioural state is, however, also associated with reduced micturition. No correlation exists between renal artery and descending aorta pulsatility indices and fetal urinary output. PMID- 7999729 TI - Chronic pelvic pain caused by residual ovaries and ovarian remnants. AB - OBJECTIVE: To determine the diagnostic effectiveness and treatment of women with chronic lower abdominal pain due to residual ovaries or ovarian remnants. DESIGN: A prospective observational study. SETTING: Tertiary referral pelvic pain clinic. SUBJECTS: Seventeen women complaining of chronic pelvic pain of up to 25 years' duration, of whom seven had residual ovaries and 10 ovarian remnant(s). MAIN OUTCOME MEASURES: Persistent lower abdominal pain, pelvic tenderness and quality of life one year post-operatively. RESULTS: Six of the seven women with residual ovaries, and nine of the 10 women with presumed ovarian remnants experienced relief of the original pain, loss of pelvic tenderness and an improved quality of life. CONCLUSIONS: Residual ovaries after hysterectomy and ovarian remnants are established causes of chronic pelvic pain. Diagnosis and surgical removal is frequently difficult. Management strategies are proposed for both conditions. PMID- 7999730 TI - A population-based, controlled study of the relation between HIV infection and cervical neoplasia. AB - OBJECTIVE: To study a geographically defined population of women exposed to a drug-related risk for human immunodeficiency virus (HIV), together with carefully matched neighbourhood controls, in order to examine (1) the proportion of different groups having cervical cytopathology screening; (2) the association between HIV infection and cervical intraepithelial neoplasia; (3) the independent effect of CD4+ lymphocyte count and duration of HIV infection; and (4) the correspondence between cervical cytopathology and colposcopically directed biopsy. DESIGN: A population-based study. SUBJECTS: All women domiciled in Lothians with the following characteristics: between 1983 and 1987 they had a history of injection drug use or a seropositive partner with a history of injection drug use; they had a pregnancy after that exposure where their serostatus was known. In addition, neighbourhood controls were identified by computer matching for the following criteria--post-code sector, housing deprivation score, age, parity, pregnancy outcome, ethnic group, year of pregnancy, smoking. MAIN OUTCOME MEASURES: Search was carried out for the cervical smear nearest in time to the index pregnancy end date, providing serostatus was known at that time. All identified smears were assessed by a cytopathologist without knowledge of clinical information, study group or serostatus. RESULTS: Of 376 women, appropriate cervical smears were identified for 336. The proportions screened in the different groups were similar. There were more abnormal smears in the seropositive group than in the drug-related seronegative (P < 0.01) or the neighbourhood control groups (P < 0.001). HIV infected women with abnormal smears had lower CD4+ lymphocyte counts (P < 0.0005). There was a reasonable correspondence between cytopathological classification and histological grading, and this was of similar strength in cases and controls (weighted kappa 0.72, 0.74). CONCLUSIONS: There is a definite relation between HIV infection and cervical intraepithelial neoplasia. This is related to immune depletion but whether this is the sole mechanism for the association is unclear. PMID- 7999732 TI - Relative influence of serum follicle stimulating hormone, age and other factors on ovarian response to gonadotrophin stimulation. AB - OBJECTIVE: To determine the relative value of the woman's age, basal follicle stimulating hormone (FSH), basal luteinising hormone (LH) and menstrual cycle pattern (all defined prior to treatment) in predicting the ovarian response to gonadotrophin stimulation for in vitro fertilisation. DESIGN: Open, descriptive cohort study. PATIENTS: One hundred and seventy-one consecutive ovulatory women undergoing their first cycle of in vitro fertilisation with ovarian stimulation after pituitary desensitisation. INTERVENTIONS: Measurement of basal (early follicular phase) and down-regulated concentrations of serum FSH and LH, and calculation of age at treatment and of median length of menstrual cycles and range of variation prior to treatment. MAIN OUTCOME MEASURES: Duration and amount of gonadotrophin stimulation to achieve follicular maturity, number of mature follicles, peak serum oestradiol concentration and number of mature oocytes, were compared between banded values of variables studied. RESULTS: Increasing basal FSH concentrations were significantly associated with reducing oestradiol levels, numbers of mature follicles and oocyte yield even when the FSH levels were still within the normal range though above average (6 to 8.9 i.u./l). There were similar but weaker associations with FSH levels after down-regulation. There were also significant differences between women over and under 40 years old in their oestradiol levels, numbers of follicles and of oocytes. Analysis of variance showed significant independent association of basal FSH with both oestradiol and numbers of oocytes, but not of age, menstrual pattern, or serum LH concentrations. CONCLUSION: Serum FSH is more sensitive than the woman's age in determining her ovarian responsiveness to stimulation. LH concentrations and menstrual cycle patterns are unhelpful. PMID- 7999731 TI - Human papillomavirus vulvitis: a new disease or an unfortunate mistake? AB - OBJECTIVE: To determine whether human papillomavirus (HPV) was responsible for symptoms in women with vulvar pruritus, pain and superficial dyspareunia who had been referred with a diagnosis of HPV vulvar disease made on clinical and/or colposcopic and/or histological grounds. DESIGN: In addition to standard clinical and laboratory investigations of the whole population, a sample of 15 test cases from the population of 71 women referred with a clinicopathological diagnosis of HPV vulvar disease, and two positive and 21 negative controls were assayed for HPV DNA. Polymerase chain reaction assays using L1 consensus primers were performed blinded to the clinicopathological diagnosis. SETTING: Dermogynaecology Clinic at Mercy Hospital for Women. SUBJECTS: Seventy-one women referred with a diagnosis of HPV vulvar disease. RESULTS: Thirteen cases which could be tested for HPV DNA were negative. Diagnoses other than HPV were found for the women's presentation in all cases. CONCLUSIONS: In the population studied, our investigations indicated that the clinicopathological diagnosis of HPV infection was incorrect and that HPV was not a cause of vulvar symptoms. We believe that the term HPV vulvitis is unfortunate as it has invited destructive treatments and drawn attention away from more likely causes of this difficult group of vulvar conditions. PMID- 7999733 TI - Frustration. PMID- 7999734 TI - Maxillofacial biomodelling. AB - The authors report the clinical applications of biomodelling with the stereolithography apparatus, a computer-controlled manufacturing technique that builds anatomically accurate skeletal models from sectional radiological data. Reference to several individual cases demonstrates how pre-operative 3-D modelling can refine the accuracy of diagnostic information, facilitate preoperative planning and surgical technique, and reduce operating time. PMID- 7999735 TI - Changes in weight and body composition after orthognathic surgery and jaw fractures: a comparison of miniplates and intermaxillary fixation. AB - OBJECTIVES: To compare the changes in postoperative weight and body composition following orthognathic surgery or jaw fractures treated by intermaxillary fixation (IMF) or miniplate osteosynthesis. DESIGN: A 4-month non-randomised prospective pilot study. Body composition was assessed using the 4 site skinfold thickness technique. The fixation method used in each case was dependent on clinical criteria alone. SETTING: Oral and maxillofacial surgery units at St James's University Hospital and the General Infirmary at Leeds. SUBJECTS: All patients were eligible for inclusion in the study if they had sustained a jaw fracture or had undergone orthognathic surgery. Patients were excluded if they had sustained polytrauma, if their sole orthognathic surgery procedure was a genioplasty and if the author was not directly involved in their management. The final study group consisted of 22 patients, 18 following surgical correction of jaw fractures and 4 following elective orthognathic surgery. Thirteen patients were managed with intermaxillary fixation and 9 patients were treated with miniplate osteosynthesis. MAIN OUTCOME MEASURES: Weight, lean body mass, total body water, fat and water free lean body mass, 1 week and 6 weeks postoperatively. RESULTS: There was no significant difference in weight loss or body composition changes between the plated and non plated groups at 1 week postoperatively. However, by 6 weeks postoperatively the IMF group had lost significantly more weight (4.5 kg) than the plated group (1.1 kg). In the plated group this weight loss resulted entirely from a loss of lean body mass (77% water), whereas in the other group it resulted from a fat loss of 1.2 kg plus a lean body mass loss of 3.3 kg (73% water). Estimated protein losses were 0.9 kg for the IMF group and 0.3 kg for the plated group. CONCLUSIONS: Intermaxillary fixation compromises nutritional status in the early postoperative period leading to loss of water, fat and protein. The results of this pilot study suggest that further investigation of postoperative weight and body composition changes after oral and maxillofacial operations is indicated. PMID- 7999736 TI - Patients' anxieties with third molar surgery. AB - There has been little study of patients' anxieties about third molar surgery despite its widespread practice. 105 patients were invited to complete questionnaires preoperatively to assess anxieties about the procedure and to assess how well it was explained. They were also asked post operatively to assess differences from expectations, accuracy of the preoperative explanation and which aspect would worry them most should the procedure be repeated. Patients generally found their worries as expected or even better. Few found events worse with only pain (12%) and paraesthesia (13%) of note. Although 88% of patients assessed pain as better than or as expected, 43% would fear it most if the procedure was repeated. Pain is the single most feared factor despite evidence that it is usually no worse than originally feared. Reassurance and adequate pain control are the most important factors to patients in third molar surgery, and this reassurance should start at operation booking rather than on admission. PMID- 7999737 TI - Odontogenic myxoma--a radiographic study of 21 tumours. AB - Radiological features of 21 odontogenic myxomas found in 14 women and 7 men were analysed. Ten of the tumors were unilocular and 11 were multilocular. Unilocular lesions were mostly located in the anterior and multilocular in the posterior areas of the jaws. Intralesional trabeculation was seen in all multilocular but only in 3 unilocular lesions. Because radiological appearance of myxoma may be essentially similar with many other lesions of the jaws careful radiological examination is mandatory for planning of proper treatment. PMID- 7999738 TI - Pathological fractures of the mandible: a diagnostic and treatment dilemma. AB - Pathological fractures of the facial bones are relatively rare. Four pathological mandibular fractures are presented and the difficulty in diagnosing the underlying cause and the dilemma of treatment choice are discussed with a review of the literature. The authors found the incidence of pathological fractures of the facial bones in their series was 0.47%. Biopsy followed by rigid internal fixation, preferably with an AO reconstruction plate bridging the area of pathology after its removal, permits normal function and allows good and undisturbed healing which will inevitably be prolonged in such cases. PMID- 7999739 TI - Is there a role for temporomandibular joint surgery? AB - In North America, surgery of the temporomandibular joint (TMJ) has made considerable progress, although significant failures have plagued this field in recent years. In spite of the controversies, surgery of the TMJ continues to have a small, but nonetheless, important role in the management of specific temporomandibular disorders (TMD). A general overview of the current thinking in TMJ surgery is presented with the clear message that careful case selection is the most essential ingredient for a successful outcome. PMID- 7999740 TI - Closure of large orocutaneous fistulas in end-stage malignant disease. AB - Expanding Silastic foam was used to close and dress a large orocutaneous salivary fistula secondary to a massive local recurrence of squamous cell carcinoma. The technique is simple, rapid, and effective. The patient found the dressing superior in every way to the traditional absorbent dressings previously supplied. We recommend this technique for the closure of large defects in the head and neck. PMID- 7999741 TI - A new disposable bite gauge. AB - A simple method for assessing mouth opening by measuring interincisal distance with a disposable bite gauge is described. In a clinical study the technique has been proven to be both reproducible and reliable. PMID- 7999742 TI - Bilateral parotid MALT lymphoma and Sjogren's syndrome. AB - A patient with Sjogren's syndrome who developed bilateral parotid lymphoma is described. The management is discussed emphasising difficult aspects of the diagnosis and treatment. PMID- 7999743 TI - An uncommon accident. PMID- 7999744 TI - Visceral leishmaniasis: an unusual cervical presentation. AB - Visceral leishmaniasis is an infectious disease with a classical clinical presentation of fever, anaemia and splenomegaly forming the three cardinal signs. A rare presentation of the disease is described where cervical lymph node enlargement was the only sign and there were no symptoms. It is emphasised that with extensive travel to and from areas of endemic leishmaniasis now established, it is important that clinicians and pathologists become acquainted with the characteristics of the disease. PMID- 7999745 TI - Extraskeletal Ewing's sarcoma of the parotid region: a case report with the detection of the tumour's immunophenotypical characteristics. AB - A case report of a malignant small round cell tumour of the parotid region, with features of extraskeletal Ewing's sarcoma is presented. Besides its rare location in the soft tissues of the parotid area, the tumour expressed focal NSE and desmin immunoreactivity, indicative of multidirectional differentiation. PMID- 7999746 TI - Citation for the presentation of the 1994 De Puy Surgical Prize to Tony Markus. PMID- 7999747 TI - Cleft lip and palate deformities in children. PMID- 7999748 TI - The changing face of maxillofacial surgeons? PMID- 7999749 TI - Full-thickness/split-thickness skin grafts. PMID- 7999750 TI - Supramolecular self-assembly of Escherichia coli glutamine synthetase: characterization of dodecamer stacking and high order association. AB - Dodecameric glutamine synthetase (GS) from bacteria is formed from two face-to face hexameric rings of identical subunits. These highly symmetrical aggregates from some bacteria, including Escherichia coli, "stack" in the presence of Zn2+ and other divalent ions to generate protein tubes (phase I) and subsequently associate side-to-side to yield "cables" and nonspecific aggregates (phase II). In order to understand the molecular mechanisms of recognition leading to this macromolecular self-assembly, the effects of solution conditions on the kinetics of these processes have been studied. These reactions have been monitored by changes in light scattering and by electron microscopy. Conditions have been established for isolation of phases I and II. At 0.04 mg of GS/mL, pH 7.0, 100 mM KCl, and 1 mM Mn2+, 25 degrees C, minimal side-to-side aggregation occurs, and the stacking reaction follows second-order kinetics, with respect to GS, at low extent of reaction. The second-order rate constants determined for phase I, initiated by Zn2+ or Co2+, demonstrate a pH optimum at 7.0-7.25, whereas phase II is favored at pHs below 6.5. The pH profile for the stacking reaction suggests that His residues are involved, and modification of 2-3 histidines/subunit with diethyl pyrocarbonate (DEPC) is sufficient to completely inhibit metal-dependent dodecamer stacking. The effect of ionic strength on GS stacking was also studied. Although hydrophobic interactions have previously been assumed to dominate this protein-protein association, both phase I and phase II of the assembly are inhibited by KCl and NaCl, suggesting that ionic interactions also play an essential role.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7999752 TI - Supramolecular self-assembly of Escherichia coli glutamine synthetase: effects of pressure and adenylylation state on dodecamer stacking. AB - Escherichia coli glutamine synthetase is a dodecamer of identical subunits, consisting of two face-to-face hexameric rings. The enzymatic activity of GS is regulated by covalent attachment of an adenylyl group to each subunit, at the edge of the ring structure (Tyr-397). In the presence of Zn2+, Cu2+, Co2+, and other divalent metal ions, the free dodecamers self-organize into protein tabules [Miller et al. (1974) Arch. Biochem. Biophys. 163, 155-171]. Here, the temperature dependence and pressure dependence of the kinetics of Zn(2+)-induced self-assembly of GS tubules have been determined for the adenylylated and unadenylylated GS. The adenylylated enzyme exhibits a bimolecular rate constant for Zn(2+)-induced stacking that is 3-fold lower than for the unadenylylated GS at temperatures ranging from 0 to 25 degrees C. The enthalpy of activation, delta H++, for both adenylylated and unadenylylated GS increases from approximately 10 kcal/mol of dodecamer interface to 20 kcal/mol of dodecamer interface upon addition of 125 mM KCl to the reaction buffer. The delta H++ values for adenylylated and unadenylylated GS are nearly identical, at each concentration of KCl, suggesting that entropic factors are responsible for the differences in rate of stacking for these forms of GS. Hydrostatic pressure markedly inhibits the stacking reaction for both adenylylated and unadenylylated GS. The activation volumes, delta V++a, for stacking are increased from approximately 50 mL/mol of dodecamer interface in the absence of KCl to approximately 65 mL/mol of dodecamer interface in the presence of 125 mM KCl.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7999751 TI - Supramolecular self-assembly of glutamine synthetase: mutagenesis of a novel intermolecular metal binding site required for dodecamer stacking. AB - Dodecameric glutamine synthetase (GS) from Escherichia coli assembles into highly ordered supramolecular protein tubes in the presence of several divalent metal ions. The molecular mechanism for this metal-induced self-assembly of the E. coli GS has been studied by molecular modeling and site-directed mutagenesis. The X ray crystal structure of the nearly identical Salmonella typhimurium GS has been used to construct a model of the "stacked" complex between two dodecamers. A complementary fit, based on steric constraints, reveals a possible interaction between the N-terminal helices from adjacent dodecamers. The amino acid side chains of His and Met residues within the helices from each of the subunits of one face of a dodecamer lie within approximately 3.5 A of the analogous side chains in the subunits from the adjacent dodecamer in the stacked complex. His-4, Met-8, and His-12 from adjacent helices provide potential ligands for a binuclear metal binding site. Replacement of each of these surface residues with aliphatic amino acids has negligible effects on the enzymatic activity, the regulation of activity via adenylylation, and gross dodecameric structure. However, the rate and extent of metal ion-mediated self-assembly of GS tubules are reduced to < 2% of the wild-type protein in the single mutants H4A, H12L, and H12D. The M8L mutant demonstrates a 3-fold decrease in the bimolecular rate constant for stacking, but electron microscopy indicates that this mutant does form stacked tubes. The cysteine-containing mutants H4C, M8C, and H12C were also constructed.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7999753 TI - Residue lysine-34 in GroES modulates allosteric transitions in GroEL. AB - The conserved residue Lys-34 in GroES was replaced by alanine and glutamic acid using site-directed mutagenesis. This residue is near the carboxy terminus of the mobile loop in GroES (residues 17-32) which becomes immobilized upon formation of the GroEL/GroES complex [Landry et al. (1993) Nature 364, 255-258]. Both charge neutralization (Lys-34-->Ala) and charge reversal (Lys-34-->Glu) at this position have little effect on the binding constant of GroES to GroEL, but they increase the enhancement by GroES of cooperativity in ATP hydrolysis by GroEL. This is reflected by a change in the Hill coefficient (at 10 mM K+) from 4.10 (+/- 0.22) in the presence of wild-type GroES to 5.17 (+/- 0.24) and 4.46 (+/- 0.14) in the presence of the GroES mutants Lys-34-->Ala and Lys-34-->Glu, respectively. The results are interpreted using the Monod-Wyman-Changeux (MWC) model for cooperativity [Monod et al. (1965) J. Mol. Biol. 12, 88-118]. They suggest that Lys-34 in GroES modulates the allosteric transition in GroEL by stabilizing a relaxed (R)-like state. PMID- 7999754 TI - Lowered temperature or binding of pyrophosphate to sites for noncatalytic nucleotides modulates the ATPase activity of the beef heart mitochondrial F1 ATPase by decreasing the affinity of a catalytic site for inhibitory MgADP. AB - Lineweaver-Burk plots for ATP hydrolysis catalyzed by bovine heart mitochondrial F1-ATPase (MF1) at 30 degrees C are biphasic, whereas they are linear at 15 degrees C. The rate of inactivation of the enzyme at 23 degrees C by 5'-[(p fluorosulfonyl)benzoyl]adenosine (FSBA), which derivatizes noncatalytic nucleotide binding sites, is about 4 times faster when loss of activity is monitored at 15 degrees C as opposed to 30 degrees C. This suggests that maximal loss of ATPase monitored at 15 degrees C is observed when a single noncatalytic site is derivatized, whereas maximal inactivation at 30 degrees C requires modification of three noncatalytic sites. Prior incubation of MF1 depleted of endogenous nucleotides (nd-MF1) with pyrophosphate (PPi) stimulates ATPase activity 2-fold when assayed at 30 degrees C and pH 8.0. This stimulation correlates with binding of [32P]PPi to the second and third binding sites for PPi to be filled. Prior binding of PPi to nd-MF1 increases the rate of inactivation of the enzyme by FSBA at 23 degrees C about 4-fold when loss of activity is monitored at 30 degrees C and pH 8.0, whereas it does not affect the rate of inactivation when loss of ATPase is monitored at 15 degrees C or loss of ITPase is monitored at 30 degrees C. This indicates that the accelerated rate of inactivation induced by PPi when assays are conducted at 30 degrees C is not due to an increased rate of derivatization of noncatalytic sites. After 85% inactivation with FSBA, nd-MF1 retains the capacity to bind 2.8 mol of [32P]PPi per mole.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7999755 TI - Spectroscopic study of Ser92 mutants of human myoglobin: hydrogen bonding effect of Ser92 to proximal His93 on structure and property of myoglobin. AB - Neutron diffraction studies have demonstrated that the hydroxyl group oxygen of Ser92(F7) is hydrogen bonded to the proximal His93(48) N epsilon H proton in myoglobin (Mb) [Cheng, X., & Shoenborn, B. P. (1991) J. Mol. Biol. 220, 381-399]. In order to examine the importance of this hydrogen bond, Ser92 was replaced with Ala and Asp in human Mb. By comparing the optical, 1H-NMR, resonance Raman, and IR spectra of Mb(S92A) in several spin and oxidation states with those of wild type Mb, it was found that the mutation causes a structural change on the heme proximal side but not on the distal side. Comparison of the NMR spectra of the cyanomet form of Mb(S92A) and Mb(WT) suggests that the imidazole plane of His93 rotates somewhat around the Fe-N delta (His93) bond upon loss of the hydrogen bond between His93 and Ser92. The 2D 1H-NMR measurements of the CO complexes show that mutation of Ser92 to Ala changes the relative position of the His97 imidazole group to the heme plane, but the change is not so drastic as reported in the crystal data of Ser92 mutant of pig Mb [Smerdon et al. (1993) Biochemistry 32, 5132-5138]. On the other hand, ligand (CO, O2) binding is only slightly affected by this mutation. From these results, we conclude that the Ser92-His93 hydrogen bond maintains the protein structure of the proximal heme pocket, but it does not strongly affect the electronic structure of the heme as well as of the His93 imidazole ring.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7999756 TI - Functions of individual gamma-carboxyglutamic acid (Gla) residues of human protein c. Determination of functionally nonessential Gla residues and correlations with their mode of binding to calcium. AB - Previous studies from this laboratory have been directed toward elucidation of the roles of individual gamma-carboxyglutamic acid (Gla) residues in Gla domain related Ca(2+)-directed properties of human protein C (PC) and activated protein C (APC). On the basis of results using recombinant variants of PC containing highly conservative (Asp) mutations of individual Gla residues, it was previously proposed that Gla6, Gla14, and Gla19 may not be essential for properties associated with the Ca(2+)-dependent conformation of the Gla domain of these proteins. In this study, we have demonstrated that radical mutations to Val of Gla residues 14 and 19 resulted in 94% and 82%, respectively, of the Gla domain related, Ca(2+)- and phospholipid- (PL-) dependent anticoagulant (APTT) activity of wild-type recombinant (wtr) APC, while [Gla6-->Val]r-APC showed a complete loss of this same activity. The more conservative mutant [Gla6-->Gln]r-APC possessed 4% of the APTT activity of wtr-APC, whereas [Gla6-->Asp]r-APC was nearly fully active. As with wtr-PC, both [Gla6-->Val]r-PC and [Gla6-->Gln]r-PC displayed Ca(2+)-dependent intrinsic fluorescence quenching, suggesting that they adopted a Ca(2+)-induced conformation. However, Ca2+ titration data suggested that these conformations were not identical to that undergone by wtr-PC. In addition, the Ca(2+)-mediated binding parameters of [Gla6-->Val]r-PC and [Gla6- >Gln]r-PC to acidic PL vesicles were found to be defective. These data were interpreted at the molecular level using a model for the Gla domain of PC based on the X-ray crystal structure of the Ca2+/bovine prothrombin fragment 1 complex.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7999758 TI - Relationship between the optimal temperature for oxidative refolding and the thermal stability of refolded state of hen lysozyme three-disulfide derivatives. AB - The temperature dependence of the efficiency of oxidative refolding was examined for hen lysozyme three-disulfide derivatives produced in Escherichia coli. Each derivative was designed to lack one of the four disulfide bridges in authentic lysozyme: delta 1 (Cys6-->Ser, Cys127-->Ser), delta 2 (Cys30-->Ser, Cys115- >Ser), delta 3 (Cys64-->Ser, Cys80-->Ser), delta 4 (Cys76-->Ser, Cys94-->Ser), delta 2Ala (Cys30-->Ala, Cys115-->Ala), and delta 4Ala (Cys76-->Ala, Cys94- >Ala). The optimal refolding temperature was lowest for delta 1 (19 degrees C) and highest for delta 4Ala (30 degrees C). The chromatographically purified, completely refolded three-disulfide species were not stable above the optimal refolding temperature in the presence of glutathione. The stability of each of them was determined from the far-UV CD thermal denaturation measurement at pH 3.9 in the absence of glutathione, where the denaturation was reversible. The transition temperature was lowest for delta 1 and highest for delta 4Ala. Precise values of difference in the transition temperature among the three-disulfide derivatives were found to correlate with those in the optimal refolding temperature. Next, the effect of glycerol, which has been shown to increase the refolding efficiency [Sawano et al. (1992) FEBS Lett. 303, 11-14], was examined for delta 1 in detail. The optimal temperature for refolding increased by 3-4 degrees C with the increase in glycerol concentration by 10%. The amount of increase in the optimal refolding temperature was nearly equal to the amount of the increase in thermal stability in the presence of glycerol of refolded and purified delta 1.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7999757 TI - Three-dimensional structure of phosphotriesterase: an enzyme capable of detoxifying organophosphate nerve agents. AB - Organophosphates, such as parathion and paraoxon, constitute the largest class of insecticides currently used in industrialized nations. In addition, many of these compounds are known to inhibit mammalian acetylcholinesterases thereby acting as nerve agents. Consequently, organophosphate-degrading enzymes are of considerable interest in light of their ability to detoxify such compounds. Here we report the three-dimensional structure of such an enzyme, namely, phosphotriesterase, as determined by single crystal X-ray diffraction analysis to 2.1-A resolution. Crystals employed in this investigation belonged to the space group P2(1)2(1)2 with unit cell dimensions of a = 80.3 A, b = 93.4 A, and c = 44.8 A and one molecule per asymmetric unit. The structure was solved by multiple isomorphous replacement with two heavy-atom derivatives and refined to a crystallographic R factor of 18.0%. As observed in various other enzymes, the overall fold of the molecule consists of an alpha/beta barrel with eight strands of parallel beta pleated sheet. In addition, there are two antiparallel beta-strands at the N terminus. The molecular model of phosphotriesterase presented here provides the initial structural framework necessary toward understanding the enzyme's broad substrate specificities and its catalytic mechanism. PMID- 7999759 TI - Position 713 is critical for catalysis but not iron binding in soybean lipoxygenase 3. AB - The role of asparagine-713 in iron atom incorporation and catalysis in soybean lipoxygenase 3 was investigated using site-directed mutagenesis. A full-length cDNA for the lipoxygenase isoenzyme was obtained from a library derived from soybeans cv. Provar. Protein with native specific activity at pH 7.4 was obtained from expression in Escherichia coli. Two recent structure reports provided conflicting views about the participation of the side chain of asparagine-694 in the coordination of the iron atom required for catalysis by lipoxygenase 1. Oligonucleotide-directed mutagenesis was employed to modify residue 713 in lipoxygenase 3 which corresponds to asparagine-694 in the sequence of lipoxygenase 1. It was found that for enzyme expressed in bacteria, asparagine was not required for iron incorporation. Histidine, alanine, and serine substitutions for asparagine-713 all produced proteins that contained iron. The histidine mutant had specific activity and catalytic characteristics comparable to the wild-type enzyme. By contrast, the alanine- and serine-substituted lipoxygenases had no detectable catalytic activity. When oxidized by product, the histidine mutant also displayed the characteristic g6 signal of the soybean enzyme in its EPR spectrum. The possibilities that the residue at position 713 acts as a metal ligand, an acid-base catalyst, and a hydrogen bonding group are considered and discussed. PMID- 7999760 TI - X-ray spectroscopy of the iron site in soybean lipoxygenase-1: changes in coordination upon oxidation or addition of methanol. AB - Iron K-edge X-ray spectroscopy (XANES and EXAFS) was used to study iron coordination in frozen solutions of soybean lipoxygenase-1 (SLO). The intensity of the 1s-->3d pre-edge transition of native iron(II) lipoxygenase is greater than what was found for six-coordinate high-spin iron(II) model complexes, but comparable to that of a five-coordinate model. This and a relatively short average bond length determined by EXAFS (2.13 A) indicate that the native lipoxygenase in our frozen samples is five-coordinate, excluding possible bonds longer than 2.5 A. The coordination of the iron(II) in native lipoxygenase changes when methanol (as low as 0.1%) or glycerol (20%) is added to the buffer prior to freezing. The addition of methanol diminishes the pre-edge transition and increases EXAFS-derived bond lengths by 0.04 A, indicating a change to six coordination. The small pre-edge feature in active iron(III) lipoxygenase suggests six-coordination. EXAFS indicates a short, 1.88 A Fe-O bond, which, given other spectroscopic and crystallographic evidence, is assigned to coordinated hydroxide. The average of the remaining bond lengths is 2.11 A. The iron coordination in iron(III) lipoxygenase is less affected by the presence of alcohols than is the site in the iron(II) enzyme. Bond valence sums indicate that the bond lengths for lipoxygenase derived from our EXAFS analyses are comparable to those of crystallographically characterized model complexes. The flexibility of the coordination number in SLON (native SLO) and the presence of an [FeIIIOH]2+ unit in SLOA (active SLO) are of possible mechanistic importance. PMID- 7999761 TI - Solution structure of dimeric Mnt repressor (1-76). AB - Wild-type Mnt repressor of Salmonella bacteriophage P22 is a tetrameric protein of 82 residues per monomer. A C-terminal deletion mutant of the repressor denoted Mnt (1-76) is a dimer in solution. The structure of this dimer has been determined using NMR. The NMR assignments of the majority of the 1H, 15N, and 13C resonances were obtained using 2D and triple-resonance 3D techniques. Elements of secondary structure were identified on the basis of characteristic sequential and medium range NOEs. For the structure determination more than 1000 NOEs per monomer were obtained, and structures were generated using distance geometry and restrained simulated annealing calculations. The discrimination of intra- vs intermonomer NOEs was based upon the observation of intersubunit NOEs in [15N,13C] double half-filtered NOESY experiments. The N-terminal part of Mnt (residues 1-44), which shows a 40% sequence homology with the Arc repressor, has a similar secondary and tertiary structure. Mnt (1-76) continues with a loop region of irregular structure, a third alpha-helix, and a random coil C-terminal peptide. Analysis of the secondary structure NOEs, the exchange rates, and the backbone chemical shifts suggests that the carboxy-terminal third helix is less stable than the remainder of the protein, but the observation of intersubunit NOEs for this part of the protein enables the positioning of this helix. The rsmd's between the backbone atoms of the N-terminal part of the Mnt repressor (residues 5-43, 5'-43') and the Arc repressor is 1.58 A, and between this region and the corresponding part of the MetJ repressor 1.43 A. PMID- 7999762 TI - 13C NMR study on conformation and dynamics of the transmembrane alpha-helices, loops, and C-terminus of [3-13C]Ala-labeled bacteriorhodopsin. AB - We have recorded 13C CP-MAS and DD-MAS NMR spectra of untreated and deionized [3 13C]-Ala-labeled bacteriorhodopsin (bR) and those cleaved with carboxypeptidase A and papain to gain insight into the conformation and dynamics of the transmembrane alpha-helices, loops, and C-terminus. It turned out that the C terminus does not contribute to the 13C CP-MAS NMR spectra of [3-13C]Ala-bR recorded at ambient temperature owing to its rapid reorientational motions, since the relative peak intensities were unchanged in spite of the enzymatic cleavages. Therefore, the 13C CP-MAS NMR peaks of bR should be ascribed both to the transmembrane alpha-helices and loops. We further distinguished the peaks of the alpha II-helix form at 16.3 ppm (60%) from those of the alpha I-helix form at 14.9 ppm (20%) by deconvolution of the respective peaks of the hydrated [3 13C]Ala-bR, as referred to the 13C chemical shift of polyalanine in hexafluoroisopropyl alcohol. The remaining CP-MAS NMR peak of [3-13C]Ala-bR at 17.2 ppm was ascribed to the loops (20%) taking a variety of turn structures. In contrast, the 13C NMR signals from the C-terminal residues were significantly enhanced by recording the dipolar-decoupled (DD)-MAS NMR spectra. Conformational features of the two different portions of the C-terminus, residues 245-248 and 231-244, were revealed by the conformation-dependent 13C signals of bR successively cleaved by carboxypeptidase A and papain, respectively. The terminal end, residues 245-248, containing two Ala residues is virtually disordered and undergoing rapid motions.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7999763 TI - Elongation of helix III of the NK-2 homeodomain upon binding to DNA: a secondary structure study by NMR. AB - The secondary structure of the homeodomain encoded by the NK-2 gene from Drosophila melanogaster, in both the free and DNA-bound states, was determined in solution using two- and three-dimensional (2D and 3D) NMR spectroscopy. Proton and 15N studies were carried out on a 77 amino acid residue protein that contains the homeodomain, which was synthesized in Escherichia coli. On the basis of NOE connectivities, vicinal coupling constants, and proton-deuterium exchange behavior, three helical segments were found that consist of homeodomain amino acid residues 10-22, 28-38, and 42-52 for the protein in the absence of DNA. The major structural differences between free NK-2 and other homeodomains are the increased internal mobility of the second helix and the shorter length of the third helix, also termed the recognition helix. Despite this shorter helix, NK-2 exhibits high-affinity binding to DNA compared to other homeodomains (kD = 2.0 x 10(-10) M; L.-H. Wang and M. Nirenberg, unpublished results). The formation of the complex of NK-2 with the duplex DNA (TGTGTCAAGTG-GCTGT) significantly increases the thermal stability of the protein. The Tm increases from 25 degrees C (free NK-2) to > 47 degrees C (DNA-bound NK-2). Also, a dramatic increase in the length of helix III is observed. In the absence of DNA, the DNA recognition helix is 11 amino acid residues long (residues 42-52), whereas in the presence of DNA, the length of this helix extends to 19 amino acids (residues 42 60).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7999764 TI - Determination of the three-dimensional structure of margatoxin by 1H, 13C, 15N triple-resonance nuclear magnetic resonance spectroscopy. AB - The solution structure of the 39-residue peptide margatoxin, a scorpion toxin that selectively blocks the voltage-gated potassium-channel Kv1.3, has been determined by NMR spectroscopy. The toxin was isotopically labeled with 13C and 15N and studied using two-dimensional homonuclear and three- and four-dimensional heteronuclear NMR spectroscopy. The final structure was determined using 501 constraints, comprising 422 NOE constraints, 60 dihedral angle constraints, 9 disulfide constraints, and 10 hydrogen bond constraints. Structures were initially determined with the program PEGASUS and subsequently refined with X PLOR. The average rms deviation from a calculated average structure for the backbone atoms of residues 3-38 is 0.40 A. A helix is present from residues 11 to 20 and includes two proline residues at positions 15 and 16. A loop at residues 21-24 leads into a two-strand antiparallel sheet from residues 25 to 38 with a turn at residues 30-33. Residues 3-6 run adjacent to the 33-38 strand but do not form a canonical beta-strand. The two additional residues of margatoxin, relative to the related toxins charybdotoxin and iberiotoxin, insert in a manner that extends the beta-sheet by one residue. Otherwise, the global structure is very similar to that of these two other toxins. The longer sheet may have implications for channel selectivity. PMID- 7999765 TI - Detection of the covalent intermediate of UDP-N-acetylglucosamine enolpyruvyl transferase by solution-state and time-resolved solid-state NMR spectroscopy. AB - Uridine diphosphate-N-acetylglucosamine (UDP-NAG) enolpyruvyl transferase from Enterobacter cloacae catalyzes the transfer of an enolpyruvyl moiety from phosphoenolpyruvate (PEP) to the 3-hydroxyl of UDP-NAG to form enolpyruvyl UDP NAG and inorganic phosphate. Indirect evidence for the involvement of a covalent intermediate, in which the C-2 of O-phosphothioketal moiety is attached to Cys 115, in the reaction catalyzed by UDP-NAG enolpyruvyl transferase has been reported by Wanke and Amrhein [Wanke, C., & Amrhein, N. (1993) Eur. J. Biochem. 218, 861-870]. In the enzyme from Escherichia coli, a noncovalent tetrahedral intermediate in which the C-2 of PEP is attached to the 3-OH of UDP-NAG via an ether linkage has been isolated by Marquardt et al. [Marquardt, J.L., Brown, E.D., Walsh, C.T., & Anderson, K.S. (1993) J. Am. Chem. Soc. 115, 10398-10399]. In this study, we provide direct evidence for the formation of a covalent O phosphothioketal enzyme intermediate from UDP-NAG enolpyruvyl transferase of E. cloacae overexpressed in E. coli. The intermediate was obtained by incubation of the enzyme with [2,3-13C2]PEP and UDP-NAG and was characterized by solution-state 1D 13C and 31P NMR, 13C DEPT NMR, and 1H[13C]2D HMQC NMR spectroscopy. The 13C NMR spectra showed two coupled resonances at 29.3 and 88.7 ppm which were assigned to the C-3 and C-2 of the covalent intermediate, and the 13C DEPT confirmed that C-3 was a methyl group and C-2 was quaternary.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7999766 TI - Residues specific for class III alcohol dehydrogenase. Site-directed mutagenesis of the human enzyme. AB - Human class III alcohol dehydrogenase (with both glutathione-dependent formaldehyde dehydrogenase and alcohol dehydrogenase activities) was expressed, and studied by site-directed mutagenesis corresponding to three amino acid residues that are affecting the substrate-binding pocket of class I (with alcohol dehydrogenase activity only). A Thr48Ala exchange results in an enzyme essentially without alcohol dehydrogenase activity but with some glutathione dependent formaldehyde dehydrogenase activity retained. This indicates that coordination to the enzyme of S-hydroxymethylglutathione is mediated by interactions additional to, or different from, those utilized for primary and secondary alcohols. An Asp57Leu mutation causes considerable loss of the formaldehyde dehydrogenase activity, showing that a negative charge at position 57 is a prerequisite for this class III-type of activity, in the same manner as a positive charge at position 115 has been previously demonstrated to be crucial. Therefore, Asp57 and Arg115 appear to contribute equally to the interactions with S-hydroxymethylglutathione, compatible with defining the class III-type of specificity and possibly explaining the dependence on glutathione. A Tyr93Phe mutant exhibits decreased kcat values for substrates in general and correlates with inhibition of alcohol dehydrogenase activity by 4-methylpyrazole, a potent inhibitor of the class I enzymes. In a double mutant, Asp57Leu/Tyr93Phe, the effects of the two mutations are potentiating one another, yielding a fall in kcat/Km for hydroxymethylglutathione by a factor of 1250, i.e., a still further loss of class III-type activity.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7999767 TI - Mechanism-based inhibition of thymidylate synthase by 5-(trifluoromethyl)-2' deoxyuridine 5'-monophosphate. AB - Thymidylate synthase (TS) from Lactobacillus casei is inhibited by 5 (trifluoromethyl)-2'-deoxyuridine 5'-monophosphate (CF3dUMP). CF3dUMP binds to the active site of TS in the absence of 5,10-methylenetetrahydrofolate, and attack of the catalytic nucleophile cysteine 198 at C6 of the pyrimidine leads to activation of the trifluoromethyl group and release of fluoride ion. Subsequently, the activated heterocycle reacts with a nucleophile of the enzyme to form a moderately stable covalent complex. Proteolytic digestion of TS treated with [2'-3H]CF3dUMP, followed by sequencing of the labeled peptides, revealed that tyrosine 146 and cysteine 198 are covalently bound to the inhibitor in the enzyme-inhibitor complex. The presence of dithiothreitol (DTT) or beta mercaptoethanol resulted in the breakdown of the covalent complex, and products from the breakdown of the complex were isolated and characterized. The three dimensional structure of the enzyme-inhibitor complex was determined by X-ray crystallography, clearly demonstrating covalent attachment of the nucleotide to tyrosine 146. A chemical reaction mechanism for the inhibition of TS by CF3dUMP is presented that is consistent with the kinetic, biochemical, and structural results. PMID- 7999768 TI - Rapid kinetics of the EPR-active species formed during initial iron uptake in horse spleen apoferritin. AB - The molecular mechanism of oxidative deposition of iron in ferritin is incompletely understood. In this study, EPR-active species produced during ferritin reconstitution (10-50 Fe/protein) from the apoprotein, Fe2+, and O2 have been investigated using rapid-mixing freeze-quench techniques and EPR spectroscopy. Species studied include a monomeric Fe(3+)-protein complex (g' = 4.3), a mixed-valent Fe(2+)-Fe3+ complex (g' = 1.87), and a newly observed radical with axial symmetry (g parallel = 2.042, g perpendicular = 2.0033), all apparent intermediates formed during the first second of iron oxidation. The monomeric Fe(3+)-protein complex is the principal EPR-observable product of iron(II) oxidation and is produced quantitatively in the first phase of the reaction with the mixed-valent species and the radical formed at slower rates. The initial rate of formation of the monomeric complex (and the radical) is first order in Fe2+ concentration, consistent with a mechanism in which iron oxidation occurs in a one-electron step(s) with H2O2 being the final product of O2 reduction. A 1:1 relationship between the disappearance of the monomeric Fe(3+) protein complex and the formation of the mixed-valent Fe(2+)-Fe3+ species was observed in the early phase of the reaction, indicating that the latter is derived from the former and not from the one-electron oxidation of a preformed Fe(2+)-Fe2+ dimer. The g-factors and rapid EPR relaxation properties of the transient radical suggest that it is associated with an Fe2+ (or Fe3+) center but its identity and possible functional role in iron oxidation are unknown. PMID- 7999769 TI - Low-temperature optical spectroscopy of native and azide-reacted bovine Cu,Zn superoxide dismutase. A structural dynamics study. AB - The optical absorption spectra of native and N(3-)-reacted Cu,Zn superoxide dismutase (SOD) has been studied in the temperature range 300-10 K. The broad d-d bands observed in the room temperature spectrum, centered at 14,700 cm-1 (native enzyme) and at 15,550 cm-1 (N(3-)-reacted enzyme), are clearly split at low temperature into two bands each, centered at 12,835 and 14,844 cm-1 and at 14,418 and 16,300 cm-1, respectively. The thermal behavior of the 23,720 cm-1 band present in the spectrum of the native enzyme indicates that this band belongs to the His61-->Cu(II) ligand to metal charge transfer transition. Analysis of the zeroth, first, and second moments of the various bands as a function of temperature allowed us to obtain useful information on the stereodynamic properties of the metal site in SOD. In particular for the native protein, it was possible to infer a variation in the metal ligand relative position that occurs as the temperature is lowered and that likely involves all of the ligands except His61. On the other hand, the site is stabilized upon N3- binding, and in this case a variation in the metal ligand position is observed only at the level of the bound anion. The possible relation of these properties to the catalytic mechanism of the enzyme is discussed. PMID- 7999770 TI - The room temperature reaction of carbon monoxide and oxygen with the cytochrome bd quinol oxidase from Escherichia coli. AB - When grown under O2-limited conditions, Escherichia coli expresses a cytochrome bd quinol oxidase that has an unusually high affinity for O2. We have studied the reaction of cytochrome bd with CO and O2 by rapid-reaction spectrophotometry. The reduced enzyme forms a photosensitive ferrocytochrome d-CO complex, and following photolysis, CO recombines with the reduced enzyme with a bimolecular rate of 8 x 10(7) M-1 s-1. Reaction of CO-bound enzyme with O2 gives a CO off-rate of 1.6 s 1. The O2 reaction is followed by a flow-flash procedure in which CO-ligated enzyme is mixed with O2, and the reaction commenced by photolysis of cytochrome d CO. In the presence of O2, two processes are resolved on a time-scale of 300 microseconds. The absorbance at 645 nm first increases at a rate that is dependent on O2 concentration with a value of 2 x 10(9) M-1 s-1. The second phase results in decreased absorbance at 645 nm and increased absorbance at 680 nm. The rate of the second process is independent from O2 concentration above 50 microM O2 and reaches a first-order limit of 1 x 10(4) s-1. A model for the reaction of the cytochrome bd quinol oxidase with O2 is proposed in which an initial ferrocytochrome d-oxy adduct forms, and then decays to a ferryl-oxo species. The oxidation of the low-spin cytochrome b component of the oxidase, monitored at 560 nm, occurs at the same time as the ferryl species forms. We suggest that the suitability of the cytochrome bd quinol oxidase to function at low O2 concentration is conferred by its rapid rate of binding O2. PMID- 7999771 TI - Novel methyltransferase activity modifying the carboxy terminal bis(geranylgeranyl)-Cys-Ala-Cys structure of small GTP-binding proteins. AB - Proteins containing CX3, CXC, and CC (where C is cysteine and X is undefined) undergo posttranslational isoprenylation at their cysteine residues. In the case of proteins which terminate in CX3, proteolytic removal of X3 is followed by the carboxymethylation of the isoprenylated cysteine residue. CXC proteins also undergo C-terminal methylation. The present study addresses the question of whether this methylation is catalyzed by a different isoprenylated protein methyltransferase than that previously described for CX3 proteins. The S adenosylmethionine (AdoMet) dependent methylation of a small peptide-N-acetyl-S geranylgeranyl-L-cysteinyl-L-alanyl-S-geranylgeranyl- L- cysteine (Ac(GG)CysAla(GG)Cys)--was investigated using membranes from a variety of bovine tissues as sources of enzyme. Ac(GG)CysAla(GG)Cys was a substrate for methylation, while Ac(GG)Cys(GG)Cys was not. Reciprocal inhibition studies on the methylation reactions of the CXC peptide and of N-acetyl-S-farnesyl-L-cysteine (AFC), a previously described methyltransferase substrate, suggested that these reactions are catalyzed by distinct enzymatic activities. Farnesylthioacetic acid (FTA), a potent competitive inhibitor of the methylation of AFC, did not inhibit the methylation of the CXC peptide. Moreover the KI values for S adenosylhomocysteine and S-adenosylethionine inhibition differed for the two enzymatic activities. These data indicate that more than one AdoMet-dependent methyltransferase is involved in the carboxymethylation of isoprenylated proteins. PMID- 7999772 TI - HMG domain proteins induce sharp bends in cisplatin-modified DNA. AB - Circularly permuted linear DNAs of approximately 100 bp were constructed containing the major adduct of the anticancer drug cisplatin, a cis [Pt(NH3)2[d(GpG)-N7(1),-N7(2)]] intrastrand cross-link, at a specific site. Gel electrophoresis mobility shift assays with these probes were used to investigate the effects of binding of HMG domain proteins to the platinated DNAs. The site specifically platinated duplexes were recognized by six different HMG domain proteins--HMG1, mtTFA, Ixr1, and HMG domains from HMG1 (domain B), mSRY, and LEF 1--with comparable binding affinities (Kd approximately 10(-6) to 10(-7) M). In the presence of the HMG domain proteins, the platinated DNAs were bent significantly more than in their absence, the values being 86 +/- 2 degrees, 87 90 +/- 5 degrees, and 68 +/- 6 degrees, respectively, for the proteins and 65-74 +/- 4 degrees, approximately 50 degrees, and 72 +/- 6 degrees, respectively, for the domains. The variability in bend angles suggests that, although the HMG domain proteins share a common ability to bend platinated DNA, specific contacts between the proteins and the platinated duplex are different. The assay further revealed the bend loci to be centered quite near the platinum adduct. The methodology employed in the present study should be generally applicable for synthesizing other small, circularly permuted, covalently modified DNAs which cannot otherwise be readily obtained. PMID- 7999773 TI - Purification and biochemical characterization of recombinant N-methylpurine-DNA glycosylase of the mouse. AB - The mouse N-methylpurine-DNA glycosylase (MPG), responsible for the removal of most N-alkyladducts in DNA, was purified to homogeneity as a recombinant nonfusion protein from Escherichia coli. Only 10-15% of the protein was present in the soluble form in E. coli cells. The N-terminal amino acid sequence of the purified protein which lacks 48 residues from the amino terminus of the wild type protein was identical to that predicted from the nucleotide sequence. The glycosylase hydrolyzes 3-methyladenine (m3A), 7-methylguanine(m7G), and 3 methylguanine (m3G) from DNA, and the Km and kcat values were 130 nM and 0.8 min 1 for m3A, and 860 nM and 0.2 min-1 for m7G, respectively, when methylated calf thymus DNA was used as the substrate. A comparison of kcat/Km values for different bases indicates that the enzyme was more efficient in excising both m3A and m3G than m7G from methylated DNA. The enzyme showed moderate binding affinities (KA) for both methylated (5.8 x 10(7) M-1) and nonmethylated DNAs (4.2 x 10(7) M-1). The mouse protein has an extinction coefficient E280nm1% of 10.5 and a pI of 9.3. The enzyme activity was optimal in the presence of 100 mM NaCl, with a broad pH optimum of 8.5-9.5. The enzymatic release of both m3A and m7G was stimulated 50-75% by 0.5 mM MgCl2 and 0.02 mM spermine but inhibited by higher concentrations of these agents. Product inhibition by 40-50% of the reaction occurred in the presence of 10 mM m3A or m7G. However, 1.0 mM m3A stimulated release of m7G. The enzyme was inhibited by 60% in the presence of 0.9 mg/mL DNA which, at the same time, protected it from thermal inactivation. PMID- 7999775 TI - Zinc and DNA binding properties of a novel LIM homeodomain protein Isl-2. AB - LIM homeodomain proteins are a family of recently characterized proteins which contain, in addition to a homeodomain, two tandem repeats of conserved Cys-His motifs termed as LIM domains. We have recently isolated several clones from a chinook salmon pituitary cDNA library that encode two novel LIM homeodomain proteins, Isl-2 and Isl-3, which are structurally related to rat Isl-1. In the present study, we used the salmon Isl-2 to determine the role of LIM domains in DNA binding. Several glutathione S-transferase (GST) fusion proteins containing either full length Isl-2 or various portions of this protein were expressed in bacteria. Zinc blot analysis reveals that the LIM domains produced in bacteria are capable of binding zinc. Gel shift analysis indicates that all homeodomain containing fusion proteins are able to bind to a TAAT target sequence while the fusion proteins containing only the LIM domain are not. In contrast to a previous observation that the LIM domains of rat Isl-1 have an inhibitory role in DNA binding, full length salmon Isl-2 containing both the LIM domains and a homeodomain can bind to a TAAT target sequence. To further examine the role of LIM domains in DNA binding, several GST fusion proteins were used to select specific target DNA sequences from a pool of randomly incorporated oligonucleotides. Specific target DNAs were selected by fusion proteins containing the homeodomain or the full length Isl-2, but not by LIM domain only fusion proteins, indicating that the LIM domain alone is not involved in DNA binding. The selected target DNAs were cloned and sequenced. They revealed two classes of consensus, C/TTAATG/TG/A and C/TTAAGTG, for both the homeodomain and full length Isl-2. The two classes of consensus competed with each other for binding to the homeodomain. The equilibrium dissociation constants for DNA binding, estimated by Scatchard analysis, were similar for the homeodomain and full length Isl-2.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 7999776 TI - Interaction sites of ribosome-bound eukaryotic elongation factor 2 in 18S and 28S rRNA. AB - The involvement of ribosomal RNA in the binding of eukaryotic elongation factor eEF-2 to the ribosome was investigated. eEF-2 was complexed to empty reassociated 80S ribosomes in the presence of the nonhydrolyzable GTP analogue GuoPP[CH2]P. The formed complex was treated with dimethyl sulfate, 1-cyclohexyl-3-(2 morpholinoethyl)carbodiimide metho-p-toluenesulfonate, and micrococcus nuclease to allow specific modification at single-stranded regions of the rRNAs. The sites of modification were localized by primer extension using complementary deoxynucleotide primers and reverse transcriptase. The modification pattern was compared to that obtained from 80S ribosomes lacking bound eEF-2. Binding of the factor to the ribosome resulted in the protection of specific sites in both 18S and 28S rRNA, while the reactivity of 5.8S rRNA was unchanged. In 18S rRNA, the affected nucleotides were localized to the 5'- and 3'-domains, and in 28S rRNA the protected nucleotides were seen in domains II, IV, and V. The alpha sarcin/ricin loop in domain VI of 28S rRNA was inaccessible for chemical modification even in the absence of bound eEF-2. However, the bound factor protected A4256, located in the alpha-sarcin/ricin loop, from ricin-induced depurination. PMID- 7999774 TI - A single stranded DNA binding protein isolated from HeLa cells facilitates Ni2+ activation of DNA polymerases in vitro. AB - The divalent nickel ion (Ni2+) is one of several metal ions that can substitute for Mg2+ in the activation of DNA polymerases in vitro, but usually with very low efficiency. We have purified and partially characterized a Ni(2+)-binding protein (p40) from HeLa cell extracts that can specifically enhance the polymerase activity of DNA polymerase alpha (pol alpha) and other DNA polymerases in response to Ni2+. This protein, with a molecular mass of 40 kDa, is a single stranded DNA binding protein that binds to a M13 DNA template-primer with an optimum stoichiometry of approximately 90 equiv of protein per equiv of DNA template and enhances the affinity of pol alpha for the primer-template. In the presence of Ni2+, p40 exhibits an increased affinity for DNA. The p40 increased by 3- to 6-fold the rates at which pol alpha and the Klenow fragment of Escherichia coli DNA polymerase I (KF) replicate different DNA templates in response to Ni2+. The low processivity of Ni(2+)-activated pol on primed M13 ssDNA was also enhanced by the presence of p40. The rates of Ni(2+)-dependent replication by inherently more processive enzymes, DNA polymerase delta and T4 DNA polymerase, were not significantly increased by p40 when M13 ssDNA was used as a template; however, p40 did increase the activity of T4 polymerase on an activated calf thymus DNA template. The protein did not stimulate Mg(2+) activated DNA replication. PMID- 7999777 TI - Thermodynamic characterization of the cooperativity of 40S complex formation during the initiation of eukaryotic protein synthesis. AB - The first step in mammalian protein synthesis is the formation of the 40S initiation complex, composed of the 40S ribosomal subunit (R), mRNA (M, here, a 10-mer oligoribonucleotide analogue containing the initiation codon), and the quaternary complex (Q, composed of eIF-2, GTP, Met-tRNA(fMet), and the ancillary protein factor Co-eIF-2C). The interdependence of the binding of R, M, and Q in forming the 40S complex is currently unclear. We have determined the thermodynamic parameters that characterize these interactions. The binary constants for R+M and Q+M were determined spectroscopically, measuring changes in the anisotropy of the fluorescence emission of 3'-fluorescein labeled M. The other binary constant, for Q+R, and the ternary constant were determined from Millipore filtration assays using radiolabeled Met-tRNA(fMet). The association constants for the binary reactions were as follows: Ka(Q,M) < or = 0.14 x 10(6) M 1, Ka(R,M) = 1.78 x 10(6) M-1, and Ka(Q,R) = 0.94 x 10(6) M-1. The binding of Q to R.M was markedly greater than that of Q to R [Ka(Q,R.M)/Ka(Q,R) > 62]. High cooperativity for this interaction occurs in either a single-site model or in lattice models for the binding of M to R. Data obtained using five other RNA 10 mers, each with the sequence altered at the AUG codon, suggest that this cooperativity is AUG dependent. The data are consistent with a scheme in which mRNA and Q bind independently to the 40S ribosome, but when the AUG codon is properly aligned with Q, a conformational change results in a 2.4 kcal/mol stabilization of the complex. PMID- 7999778 TI - Contribution of the surface free energy perturbation to protein-solvent interactions. AB - Surface tension measurements were carried out at 20 degrees C by a capillary drop weight method on aqueous solutions of sodium glutamate (NaGlu), lysine hydrochloride (LysHCl), potassium aspartate (KAsp), arginine hydrochloride (ArgHCl), lysylglutamate (LysGlu), argininylglutamate (ArgGlu), guanidinium sulfate, trehalose, trimethylamine N-oxide (TMAO), dimethyl sulfoxide, 2-methyl 2,4-pentanediol (hexylene glycol), and poly(ethylene glycol)s of molecular weights 200, 400, 600, and 1000. All of the salts and the sugar increased the surface tension of water, while the last four compounds decreased it, with 2 methyl-2,4-pentanediol lowering it most effectively and TMAO being the least effective. The preferential hydration of bovine serum albumin (BSA) and lysozyme was measured in KAsp, ArgHCl, LysGlu, and ArgGlu. The high values of preferential hydration found in all cases, except for BSA in ArgHCl, suggest that they should stabilize protein structure, as had been found for lysine hydrochloride and monosodium glutamate [Arakawa, T., & Timasheff, S. N. (1984) J. Biol. Chem. 259, 4979-4986]. A correlation was found for both BSA and lysozyme in KAsp, NaGlu, LysHCl, ArgGlu, and LysGlu between the surface tension effect and the observed preferential interactions, indicating that the change in the surface free energy of the protein-containing cavity due to the surface tension increase for water by these amino acid salts contributes dominantly to the observed increase in the chemical potential of the protein by their addition. The lack of a correlation observed for BSA, but not lysozyme, in ArgHCl at low concentrations where preferential binding is close to zero suggests, however, that the surface tension effect is not the sole factor involved in the protein-solvent interactions in these amino acid salts. Binding of ArgHCl to BSA, probably through hydrogen bonds between the Arg guanidinium group and peptide bonds, was proposed to occur, the affinity of Arg+ being reduced by electrostatic repulsion when proteins carry a net positive charge, such as is the case with lysozyme. Since the four organic solvent additives also lead to protein preferential hydration, no correlation exists between their preferential interactions and the surface free energy perturbation. Therefore, in their case, the preferential hydration must be ascribed to other factors that overcome the preferential binding expected from the Gibbs adsorption isotherm. The surface tension results, however, are consistent with the binding of the organic solvents to proteins through hydrophobic interactions, explaining, at least in part, the observed concentration dependence of the interactions. PMID- 7999779 TI - Effects of particle size on cell uptake of model triglyceride-rich particles with and without apoprotein E. AB - The effect of apoprotein E on cellular uptake of "VLDL-size" and "IDL-size" triacylglycerol-phospholipid emulsion particles was studied in J-774 macrophages and fibroblasts. In the absence of apoprotein E (apo E), uptake of the smaller IDL-size particles was up to 2-fold higher by mass and 100-fold higher as calculated by particle number. Apo E enhanced the uptake of both VLDL-size and IDL-size emulsion particles, but the effect was greater on the uptake of larger particles (4-5-fold) as compared to up to a 2-fold increase in the uptake of IDL size particles. In fibroblasts, particle uptake was less than in macrophages (30 50%), but preferential uptake of smaller particles was similarly observed. Particle internalization was demonstrated by 125I-apo E degradation and resistance to particle release by heparin-suramin. In the absence of apo E, cholesteryl ester of emulsion particles (prepared with trace amounts of [3H]cholesteryl ester) was hydrolyzed to free cholesterol, proving internalization and intracellular metabolism. Double-label experiments using DiI labeled emulsion particles, in the absence and presence of apo E, showed that emulsion particles are rapidly targeted to perinuclear lysosomes. Thus, at physiological concentrations of triglyceride-rich particles, non-receptor mediated uptake is a mechanism for the uptake of VLDL-size and IDL-size particles into cells. PMID- 7999780 TI - Role of two acetylcholine receptor subunit domains in homomer formation and intersubunit recognition, as revealed by alpha 3 and alpha 7 subunit chimeras. AB - Differential expression of subunit genes from the nicotinic acetylcholine receptor (AChR) superfamily yields distinct receptor subtypes. As each AChR subtype has a specific subunit composition and many subunit combinations appear not to be expressed, each subunit must contain some information leading to proper assembly. The neuronal AChR subunits alpha 3 and alpha 7 are expressed in bovine chromaffin cells, probably as constituents of two different AChR subtypes. These subunits have different assembly behavior when expressed in heterologous expression systems: alpha 7 subunits are able to produce homomeric AChRs, whereas alpha 3 subunits require other "structural" subunits for functional expression of AChRs. This feature allows the dissection of the requirements for subunit interactions during AChR formation. Analysis of alpha 7/alpha 3 chimeric constructs identified two regions essential to homomeric assembly and intersubunit recognition: an N-terminal extracellular region, controlling the initial association between subunits, and a second domain within a region comprising the first putative transmembrane segment, M1, and the cytoplasmic loop coupling it to the pore-forming segment, M2, involved in the subsequent interaction and stabilization of the oligomeric complex. PMID- 7999781 TI - Structure of the mouse dipeptidyl peptidase IV (CD26) gene. AB - Dipeptidyl peptidase IV (DPP IV, EC 3.4.14.5) is an ectopeptidase whose expression is modulated during thymocyte differentiation and T cell activation. We describe here the organization of the mouse DPP IV gene. This gene, which encompasses more than 90 kb, is composed of 26 exons separated by introns, the lengths of which vary from 100 bp to more than 20 kb. Reverse PCR performed on RNA from different tissues indicated that DPP IV transcripts do not contain alternatively spliced CDS sequences and, therefore, are supposed to yield a single polypeptide. However, two types of specific mRNA have been detected that differ in their 3'UTR sequences. They derive from alternative polyadenylation of the DPP IV primary transcript, since the different 3'UTR sequences are contiguous in the mouse DPP IV gene. Sequence analysis of the gene 5'-flanking region revealed several structural features found in the TATAA-box-less promoters, including a G+C-rich segment, a high frequency of dinucleotide CpG, and an imperfect symmetrical dyad. The DPP IV gene was assigned by in situ hybridization to the mouse [2C2-2D] region, which is syntenic with human chromosome 2. These data indicate that the human Dpp4 locus is located within this synteny region (i.e., 2q14-q37). The genomic organization of the mouse DPP IV gene is compared to that of classical serine proteases and serine hydrolases. As structural and mechanistic conservation in the absence of sequence similarity is the most remarkable feature among alpha/beta hydrolases [Ollis, D. L., et al. (1992) Protein Eng. 5, 197-211], we report the possible evolutionary link between the DPP IV related family and alpha/beta hydrolases. PMID- 7999782 TI - Chromatin and nuclear assembly: experimental approaches towards the reconstitution of transcriptionally active and silent states. PMID- 7999783 TI - Cloning and expression of the axolotl proto-oncogene ski. AB - In vitro and in vivo overexpression studies have demonstrated that the c-ski proto-oncogene can influence proliferation, morphological transformation and myogenic differentiation. We report the isolation and expression of an axolotl (Ambystoma mexicanum) c-ski (aski) gene. Sequence analysis revealed a high degree of nucleotide and predicted amino acid (AA) homology with mammalian and anuran c ski, showing the highest conservation to Xenopus laevis c-ski (74% nucleotide and 87% AA). Northern analysis showed that axolotl c-ski is expressed in unfertilized eggs and at increasing levels in embryos from blastula to tadpole stage. c-ski expression was also detected in larval limb muscle and in several stages of regenerating limb blastemas. These data indicate that axolotl c-ski is highly conserved among amphibians and mammals and suggests that it plays a role in urodele embryogenesis and limb regeneration. PMID- 7999784 TI - Human N-methyl-D-aspartate receptor modulatory subunit hNR3: cloning and sequencing of the cDNA and primary structure of the protein. AB - Several cDNA clones encoding the human N-methyl-D-aspartate receptor modulatory subunit hNR3, were isolated from a human fetal brain library. The hNR3 cDNA demonstrated a 91.3-91.5% nucleotide (nt) identity with the rat NR2B and mouse epsilon 2 cDNAs. The nt sequence of hNR3 would encode a 1484 amino acid (aa) protein that has a 98.4-98.5% identity with the mouse epsilon 2 and rat NR2B subunits. PMID- 7999785 TI - Cloning and expression analysis of a cytochrome P-450(11 beta) cDNA in sheep. AB - A full length ovine steroid 11 beta-hydroxylase (cytochrome P-450(11 beta)) cDNA clone from a sheep adrenal cortex cDNA library was isolated. Sequence analysis indicates that this cDNA clone resembles bovine P-450(11 beta) cDNA (95% nucleotide sequence homology) more closely than rat P-450(11 beta) cDNA (69% nucleotide sequence homology). Although the levels of nucleotide sequence homology of this cDNA clone to the rat P-450(11 beta) cDNA and the rat P-450aldo cDNA are similar, the putative amino acid sequence shows a closer resemblance to rat P-450aldo protein. Northern blot analysis shows that there are three sizes of transcript and they are expressed throughout the adrenal cortex. PMID- 7999786 TI - The primary structure of rat ribosomal protein L22. AB - The amino acid sequence of the rat 60S ribosomal subunit protein L22 was deduced from the sequence of nucleotides in two recombinant cDNAs. Ribosomal protein L22 has 128 amino acids; the molecular weight is 14,779. Hybridization of the cDNA to digests of nuclear DNA suggests that there are 6 to 9 copies of the L22 gene. The mRNA for the protein is about 600 nucleotides in length. Rat L22 is related to ribosomal proteins from other eukaryotes and is identical in amino acid sequence to human EAP, the EBER 1 (Epstein-Barr virus encoded RNA) associated protein. PMID- 7999787 TI - Characterization of a bovine mammary gland PP3 cDNA reveals homology with mouse and rat adhesion molecule GlyCAM-1. AB - A full length PP3 (Proteose-Peptone component 3) cDNA of 679 bp was isolated from a bovine mammary gland cDNA library. The cDNA encodes a signal peptide of 18 amino acids followed by the mature PP3 sequence of 135 amino acids. This polypeptide showed homology with mouse and rat GlyCAM-1 (Glycosylation dependent Cell Adhesion Molecule 1) a protein which has been shown to act as a ligand for lymphocytes. The similarity was most profound between the signal peptides and three short regions of the mature polypeptides. Additionally structural conservation was predicted by computer analysis in the shape of a C-terminal amphipathic helix. PP3 was found to be expressed in mammary gland but not in peripheral lymph nodes, Peyer's pathes, lung, spleen, heart, and muscle. PMID- 7999788 TI - Molecular cloning of a maize cDNA clone encoding a putative proliferating cell nuclear antigen. AB - We report the isolation and sequence of a maize cDNA clone which encodes a protein homologous to proliferating cell nuclear antigen (PCNA). The deduced amino acid sequence predicts a protein of 263 amino acids in length. The amino acid sequence shares 62% identity with the human PCNA and 95% identity with the rice homologue of PCNA. PMID- 7999789 TI - Baculovirus expression of human basic fibroblast growth factor from a synthetic gene: role of the Kozak consensus and comparison with bacterial expression. AB - Synthetic genes encoding the 146 and 155 amino acid forms of human basic fibroblast growth factor (bFGF) were constructed with codon usage biased towards the polyhedrin-encoding gene of Autographa californica nuclear polyhedrosis virus (AcNPV). Expression of both bFGF genes in Spodoptera frugiperda (SF-21) suspension cell culture using a recombinant baculovirus yielded approximately 2.5 mg of mitogenically fully active protein per 10(9) cells following heparin affinity chromatography. To improve translational efficiency, the Kozak consensus sequence was introduced and it was found that neither the replacement of a pyrimidine by a purine at position -3, nor the nature of the base at position +4 had any noticeable effect on the final levels of bFGF expression in SF-21 cells. The bases at these critical points in the consensus do not therefore play a major role in expression levels of the bFGF synthetic genes. The two synthetic genes were also expressed in Escherichia coli as native proteins using the T7 expression system. 5 mg of mitogenically fully active bFGF were obtained from 1 l of bacterial culture. Both insect cell- and E. coli-derived bFGF were equally mitogenic for Swiss 3T3 fibroblasts. PMID- 7999790 TI - Regulation of mammalian S-adenosylmethionine decarboxylase as studied in a transient expression system. AB - Mammalian S-adenosylmethionine decarboxylase (AdoMetDC), which catalyzes a key step in the biosynthesis of polyamines, is regulated by a multitude of mechanisms. The polyamines exert a strong feedback control of the enzyme. In the present study we have used a transient expression system to study the regulation of mammalian AdoMetDC. COS cells were transfected with a SV 40-based expression vector containing a 5'- and 3'-truncated human AdoMetDC cDNA (pSDC:16). The cells were shown to contain high levels of AdoMetDC activity 2 days after expression. This was partly due to an increase in the synthesis of the enzyme. However a marked stabilization of the enzyme against degradation did also contribute to the high AdoMetDC activity seen in the COS cells after the transfection with pSDC:16. The high expression of AdoMetDC was reflected in a marked change in intracellular polyamine levels. The cells were almost depleted of their putrescine, and their spermidine content was decreased to about 35% of that found in the mock transfected cells. The spermine content, on the other hand, was increased. This change in polyamine levels was most likely attributable to the pSDC:16-induced increase in decarboxylated S-adenosylmethinine, which favors the accumulation of spermine at the expenses of putrescine and spermidine. The effects on the expression of AdoMetDC of polyamine synthesis inhibitors varied dependent on whether the COS cells were transfected with control vector or pSDC:16, in spite of similar effects on cellular polyamine levels, indicating a difference in feedback regulation of 'native' and recombinant AdoMetDC. The construct used in the present study gave rise to an AdoMetDC mRNA without a 5' and devoid of most of the 3' untranslated regions. However, whether these parts of the mRNA are involved in the polyamine-mediated translational control of the enzyme remains to be confirmed. PMID- 7999791 TI - High level expression of human leukemia inhibitory factor (LIF) from a synthetic gene in Escherichia coli and the physical and biological characterization of the protein. AB - LIF is a multi-functional cytokine that elicits effects on a broad range of cell types. In this report, we present the high level expression of human LIF (hLIF) from a chemically synthesized gene template in Escherichia coli where it comprises up to 25% of the cellular protein. The recombinant hLIF, after purification and folding, was examined using CD, FTIR spectroscopy and light scattering. CD and FTIR spectra showed that the hLIF is an alpha-helical protein and has a distinct tertiary structure. The IFTR spectrum resembles that of other four helical bundle proteins including G-CSF and IL-6. Light scattering analysis indicated that it is a monomeric protein, distinguishing it from M-CSF and interferon gamma, which also belong to the class of four helical bundle proteins but are dimeric. Recombinant hLIF was assayed for its activity on the murine leukemic cell line, M-1 as well as on human leukemic cell line, ML-1. It inhibited the growth of M-1 cells and differentiated them towards macrophages. However, it did not have any differentiation inducing effect on human leukemic cell lines alone or in combination with other cytokines. PMID- 7999792 TI - Topoisomerase I is differently phosphorylated in two sublines of L5178Y mouse lymphoma cells. AB - Two sublines of LY murine lymphoma, differing in sensitivity to CPT, served as source of topoisomerase I in order to compare the enzyme's properties. The activity of topoisomerase I isolated from LY-S cells of reduced sensitivity to CPT increased about 2-times more upon phosphorylation with casein kinase but was inhibited to a lesser extent upon dephosphorylation with alkaline phosphatase than the enzyme from the CPT-sensitive LY-R cells. The in vitro phosphorylation of LY-S enzyme restored its sensitivity to CPT. The in vitro incorporation of 32P into topoisomerase protein was about 1.7-times higher in LY-S than in LY-R enzyme. A reversed incorporation ratio was observed upon metabolic labelling. The level of topoisomerase I protein, determined by Western blot analysis using scleroderma anti-topoisomerase I antibodies, was about 1.5-times higher in LY-S than in LY-R cells. The level of topoisomerase I mRNA was similar in both sublines. These results indicate that the reduced sensitivity of LY-S cells to CPT is based on the lowered phosphorylation of topoisomerase I protein but does not depend on the expression of topoisomerase I gene. PMID- 7999793 TI - Recombination of endogenous D2 dopamine receptor gene with a metallothionein promoter in GH4C1 cells confers functional and inducible D2 response. AB - We have previously shown that expression of a functional endogenous D2 short dopamine receptor is obtained in GH4C1 cells following transfection with a plasmid that confers resistance to neomycin (pRSVNeo) (Allard et al. (1993) Biochem. Biophys. Res. Commun. 193, 801-807). In order to better understand the mechanisms responsible for such a phenomenon, we cloned and sequenced the 5' region of the D2 gene present in native GH4C1 cells as well as the cDNA of transfected cells. No homology with the published sequence of the rat D2 dopamine receptor promoter was found; however, this region has perfect homology with the mouse metallothionein promoter. In cells expressing D2 receptor, the promoter is fully functional and can regulate dopaminergic D2 receptor mRNA levels and receptor expression in a dose-dependent manner in the presence of Zn2+ or Cd2+. The receptor level is raised from 500 to 3000 fmol/mg of protein in the presence of 100 microM of Zn2+. These results suggest that in GH4C1 cells, a recombination between the mouse metallothionein promoter and the D2 dopamine receptor took place. This system provides us with a cell line expressing an endogenous dopamine D2 receptor in which the level of expression can be easily modulated. PMID- 7999794 TI - Molecular cloning and functional expression of a cDNA for mouse squalene synthase. AB - Using a probe obtained by PCR amplification, a full-length cDNA encoding squalene synthase was isolated from a mouse liver cDNA library. Its nucleotide sequence had an open reading frame fro a 416 amino acid polypeptide (calculated molecular mass, 48 kDa). In vitro transcription of the cDNA followed by in vitro translation produced a protein of the expected size. The deduced amino acid sequence was 93%, 88% and 46% identical to those of the rat, human and budding yeast squalene synthases, respectively. Blotting analyses showed that the mRNA is 1.6 kb in size and that less than two copies of the gene are present in the mouse genome. To establish the enzyme activity, the entire coding region was subcloned into an expression plasmid so that it was in frame with the N-terminal region of beta-galactosidase. Escherichia coli, which was transformed with the recombinant plasmid, expressed high activity of converting farnesyl diphosphate into squalene. PMID- 7999796 TI - Cloning and expression of two mRNAs encoding structurally different crustacean hyperglycemic hormone precursors in the lobster Homarus americanus. AB - The crustacean hyperglycemic hormone (CHH) of the X-organ sinus gland complex is a multifunctional neurohormone primarily involved in the regulation of blood sugar levels. HPLC analysis of lobster sinus glands revealed two CHH immunoreactive groups, each consisting of two isoforms with identical amino acid sequences and molecular weights. In order to obtain more information concerning the number and sequences of preproCHHs, and to study their expression, we isolated two full-length cDNAs encoding two different CHH preprohormones. Both preprohormone structures consist of a signal peptide, a CHH-precursor-related peptide and a highly-conserved CHH peptide. Expression studies revealed that the X-organ is not the only source of CHH mRNA because the ventral nerve system also expresses this mRNA. Based on these findings and earlier studies on the effect of eyestalk ablation, implantation of thoracic/abdominal ganglia as well as the multifunctionality of CHH, we postulate that CHH, present in the ventral nerve system is a good candidate for a supplementary role in the control of reproduction and molting. PMID- 7999795 TI - Identification of two splice isoforms of mRNA for mouse hepatocyte nuclear factor 4 (HNF-4). AB - Hepatocyte nuclear factor 4 (HNF-4) is a liver-enriched transcription factor involved in the expression of many liver-specific genes. In the preceding communication (Hata, S., Tsukamoto, T. and Osumi, T. (1992) Biochim. Biophys. Acta 1131, 211-213), we reported the presence of two isoforms of mRNA for HNF-4 in rat liver and kidney. The longer isoform contained a segment of 30 bases which was not present in the shorter one. As an initial step to determine whether or not other mammals have these mRNA isoforms, we isolated a cDNA for mouse HNF-4 using the rat HNF-4 gene as a probe. The cDNA had an open reading frame for a 465 amino acid polypeptide. The deduced amino acid sequence was remarkably conserved between mouse HNF-4 and rat HNF-4 (99.6% identical). Moreover, like the cDNA for the larger rat isoform, the mouse cDNA contained an extra segment of 30 bp in the coding region near the C-terminus. Blotting analyses showed that the mRNA is about 3.7 kb in size and that a single copy of the gene is present in the mouse genome. Next we carried out the polymerase chain reaction (PCR) using primers located just upstream and downstream of the extra segment. Two PCR products were amplified from a mouse liver cDNA library. Determination of their nucleotide sequences proved that they exactly corresponded to the two rat isoforms. Finally, we amplified a DNA fragment (1.1 kb in size) from mouse genomic DNA using the same PCR primers as above. Its nucleotide sequence unequivocally confirmed that different splice donor sites were used to generate the two isoforms. PMID- 7999797 TI - Structural organization of the gene for CD40 ligand: molecular analysis for diagnosis of X-linked hyper-IgM syndrome. AB - CD40 ligand (CD40L) on activated T cells plays a crucial role for Ig heavy-chain class switching and the mutation of the gene for this ligand in the X-chromosome causes immunodeficiency with hyper-IgM (X-HIM). We isolated and characterized the human genomic clone for CD40 L to obtain information about the transcriptional regulatory regions of the gene and to develop a molecular diagnostic method for X HIM patients. The genomic DNA isolated was over 12 kb long containing 5 exons that cover full sequence of mRNA for the ligand. DNA motif analysis based on transcription factor database revealed the presence of a GATA 1 box at around 265 bp. The typical TATA box, CAT site or GC rich region was not found in the 5' flanking region. However, two possible TATA like sequences were found at around 27 and -136 bp. Using the oligonucleotide primers corresponding to the introns, we performed a PCR-SSCP analysis of each exon from a patient with X-HIM syndrome and detected abnormality in exon 5. When sequenced, dinucleotide deletion in this exon was found in the patient and in one X allele of his mother as the only different sequence from that of the control gene. This procedure is simple and could be used for diagnosis of the X-HIM syndrome. PMID- 7999798 TI - Repression of transient expression by DNA methylation in transcribed regions of reporter genes introduced into cultured human cells. AB - We developed a convenient method to methylate all CpG dinucleotides in both strands in a selected region of a plasmid, and investigated the effect of DNA methylation in the transcribed regions of reporter genes on the transient expression in HeLa cells. In a construct containing the chloramphenicol acetyltransferase (CAT) gene linked to the SV40 early promoter, methylation in the CAT structural gene repressed CAT activity. Methylation in the transcribed region of the Escherichia coli lacZ gene driven by the human cytomegalovirus immediate early promoter also inhibited expression of beta-galactosidase activity. These results suggest that methylation in the transcribed region as well as promoter methylation may affect transcription. PMID- 7999800 TI - Dielectric studies of ion fluctuation and chain bending in native DNA. AB - The high-frequency dielectric dispersion exhibited by solutions of native DNA is characterised as a function of electrolyte concentration, counterion type, temperature and pH. The data are interpreted in terms of counterion fluctuation along short segments (subunits) of the DNA chain. From calculation of the subunit length from dielectric relaxation time and increment, information is derived regarding the static and dynamic bending of the DNA chain. Activation enthalpies for the ion fluctuation process are obtained from temperature-dependent dielectric data. PMID- 7999799 TI - Site-directed mutagenesis of the M13 gene 5 protein: the role of Arg-21, Tyr-26 and Tyr-41. AB - The gene 5 protein of bacteriophage M13 is a single stranded DNA binding protein essential for phage replication. We have generated the mutations R21A, Y26F and Y41A in the gene 5 protein and purified the mutant proteins for functional characterisation in vitro. The complex of Y26F with single-stranded DNA is disrupted at 0.8 M NaCl, the same salt concentration as that required to dissociate the native complex. However, the mutant proteins R21A and Y41A are considerably less stable and dissociate from single-stranded DNA at at 0.4 M NaCl. The fluorescence of the mutant proteins and the DNA-protein complexes they form has been compared with the wild-type protein to allow an assessment of the contribution from individual residues. We conclude that the fluorescence of Tyr 26 is 50% quenched in the complex with DNA, whereas that of Tyr-41 is fully quenched. Fluorescence titrations of the mutant proteins with poly(dT) show that all three mutant proteins can bind DNA but, in the case of Y41A, with a change of stoichiometry suggesting a loss of cooperativity. Gel retardation analysis of Y41A also shows anomalous behaviour in binding to oligonucleotides, consistent with the proposed involvement of Tyr-41 in dimer-dimer contacts in the nucleoprotein complex. PMID- 7999801 TI - The SMS1 gene encoding a serine-rich transmembrane protein suppresses the temperature sensitivity of the htr1 disruptant in Saccharomyces cerevisiae. AB - A new gene (SMS1; serine-rich multi-copy suppressor) of Saccharomyces cerevisiae was isolated by the ability to suppress the temperature sensitivity of the htr1 disruptant (Kikuchi et al. (1994) Mol. Gen. Genetics, in press) by increasing its gene dosage. The predicted gene product contains a serine-rich domain followed by a putative transmembrane region. The SMS1 gene was physically and genetically mapped in the region near cdc3 on chromosome XII R. PMID- 7999802 TI - Cloning and expression of human tyrosine aminotransferase cDNA. AB - Complementary DNA clones encoding human tyrosine aminotransferase (TAT) were isolated by screening a normal adult woman liver lambda gt11 library with rat TAT cDNA. The largest isolated cDNA is 2051 bp long (EMBL accession number X55675). This cDNA was subcloned downstream of the cytomegalovirus promoter in the pCMV vector for transfection into human cervical carcinoma HeLa cells. Expression of the TAT cDNA resulted in the synthesis of a protein with a molecular mass of approximately 50 kDa, as assessed by Western analysis, a value which is in close agreement with the predicted molecular weight of 50,399, for a deduced sequence of 454 amino acids. The expressed protein catalyzed specifically the conversion of L-[14C]tyrosine into p-[14C]hydroxyphenylpyruvate. The availability of a functional TAT cDNA provides a useful tool for detailed study of the structure function relationship of the enzyme and its mutated derivatives. PMID- 7999803 TI - Selected papers from the 14th annual conference on peritoneal dialysis. Orlando, Florida, January 24-26, 1994. PMID- 7999804 TI - Comparison of quality of life in hemodialysis and peritoneal dialysis patients. AB - This study was designed to compare severity of illness and quality of life variables in chronic peritoneal dialysis (PD) and hemodialysis (HD) patients. The patient sample consisted of 63 PD patients (38 male, 25 female; mean age 54.5 years) and 35 HD patients (23 male, 12 female; mean age 54.9 years). Disease severity was greater in in-center HD patients than in PD patients (p < 0.008), although there were no significant differences in functional status as measured by the Karnofsky Index between HD patients (68.6 +/- 2.3) and PD patients (71.9 +/- 1.7). While both patient groups reported the same number of overall physical symptoms. HD patients reported significantly greater overall discomfort from symptoms than PD patients (p < 0.008). In terms of psychological adjustment, analyses revealed that 22 PD patients (36.7%) and 9 HD patients (25.7%) were classified as clinically depressed. PD patients reported higher anxiety scores than HD patients (p < 0.02) and lower positive mood scores (p < 0.021). HD patients were more severely ill and appeared to suffer from physical symptomatology to a greater degree than PD patients, although they were not more impaired in terms of functional status. Moreover, HD patients showed better psychological adjustment along several dimensions when compared to PD patients. One reason for this finding may be that PD patients experience greater distress, and isolation due to a lack of social support from similar others and medical staff in comparison to in-center HD patients. PMID- 7999805 TI - Computer interaction: catheters. AB - A computer interaction session conducted during the 14th Annual Peritoneal Dialysis Conference in Orlando, Florida, on January 24, 1994, revealed the preferences and practices of 650-690 respondents voting on questions related to peritoneal catheters. Compared to the surveys conducted in 1987 and 1989, the most striking change was an increase in the use of catheters with the bent intramural segment, particularly the Swan neck catheter, and an increase in the use of catheters with the coiled intraperitoneal segment. The Tenckhoff catheter continued to be the most popular, although its use was decreasing. The remaining catheters were used in small numbers. The vast majority of nephrologists remain convinced of the superiority of double cuff catheters over single cuff ones, and the use of the former continued to exceed 70%. Essentially no change occurred in the method of catheter placement; surgical dissection (72.7%) remained the most popular implantation method. Surgeons were primarily responsible for catheter implantations (87.4% of votes). The use of prophylactic antibiotics prior to catheter implantation seems to be increasing. The majority of respondents did not consider a Staphylococcus aureus nasal carrier status as important in the development of catheter-related infections, as indicated by the small number of centers where routine culture of nares was performed. The majority of institutions delayed ambulatory peritoneal dialysis after catheter implantation, but ambulatory peritoneal dialysis was started in some centers (5.7% of votes) in the immediate postimplantation period. PMID- 7999806 TI - A new test for tidal peritoneal dialysis prescription. AB - Prediction of suitability of patients for tidal peritoneal dialysis (TPD) treatment based on the peritoneal equilibration test (PET) may be hypothetically subject to errors, due to the difference between the long equilibration times of the PET and the short dwell times currently utilized during TPD. Eleven patients, mean age 12.4 +/- 3.3 years, mean body weight 34.2 +/- 15kg, had both a standardized TPD run (initial fill volume 40 mL/kg, tidal volume 50%, dwell time 10 min, treatment time 8 h) and a PET performed. D/P ratios for creatinine and urea were calculated at the 5th and 7th TPD exchanges (approximating equilibration time of the TPD run), at the time points of the PET and on the total TPD dialysate volume. D/P ratios for creatinine and urea of the 5th and, even more, the 7th TPD exchange, and D/P ratios obtained from total TPD dialysate were significantly correlated overall (r = 0.96, p < 0.0001 for 5th D/P creatinine and urea; r = 0.98, p < 0.0001 for 7th D/P creatinine and urea). Correlation coefficients between PET-derived and total TPD dialysate-derived D/P ratios were generally poor or only modest. Thus, it is possible to predict TPD clearance, and consequently the suitability of patients for TPD, knowing the D/P ratios for creatinine and urea at the 7th TPD exchange of a standardized TPD run. Our data could represent a new reliable test for TPD prescription. PMID- 7999807 TI - Intraperitoneal versus subcutaneous insulin in patients on nighttime IPD. AB - For the diabetic patient on peritoneal dialysis, the intraperitoneal administration of insulin can lead to improvement in glycemic control while eliminating uncomfortable subcutaneous injections. Furthermore, the relatively higher portal vein concentrations of insulin compared to peripheral levels is reminiscent of the physiologic state in which the portal vein carries the insulin secreted by the pancreas. The pharmacokinetics of intraperitoneal insulin depends upon whether the insulin is administered along with the usual volume of dialysis fluid or is given undiluted. This variability has important implications for glycemic control in the patient receiving cycler peritoneal dialysis, particularly if the abdomen is dry for prolonged periods during the day. Recommendations are made based on the known pharmacokinetics of intraperitoneal insulin in both the dry and filled peritoneal cavity. PMID- 7999809 TI - Comparison of intramuscular versus subcutaneous erythropoietin for the treatment of anemia in CAPD patients. AB - Recombinant human erythropoietin (rHuEpo) can be administered to continuous ambulatory peritoneal dialysis (CAPD) patients subcutaneously (SC), intravenously (IV), and intraperitoneally (IP). Subcutaneous rHuEpo is preferred in CAPD patients because of its ease of administration and favorable pharmacokinetics. The longer half-life of SC rHuEpo allows for one or two doses per week. Since SC rHuEpo can cause pain and local irritation at the injection site, the efficacy and safety of intramuscular (IM) rHuEpo were compared to SC rHuEpo in 6 random stable CAPD patients. The protocol in each subject consisted of a single weekly injection of IM rHuEpo for 3-6 months (period 1), crossover to SC rHuEpo for 3-6 months (period 2), and crossover to IM rHuEpo for 3-6 months (period 3). The rHuEpo dose was adjusted by protocol to achieve a target hematocrit of 30%-33%. Pain at the injection site was graded on a scale of 0-3. All patients preferred IM rHuEpo to SC rHuEpo because of less pain at the injection site. One patient tolerated IM rHuEpo for six months (period 1), then left the study after one month of SC rHuEpo because of ecchymoses and pain at the SC injection sites. In all patients, there was no significant difference in the dose of rHuEpo (U/kg/wk) during the three study periods.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7999808 TI - Low-volume supine peritoneal dialysis in a chronic obstructive airway disease patient. AB - Continuous ambulatory peritoneal dialysis (CAPD) may not be tolerated by patients with chronic obstructive pulmonary disease (COPD) because of increased abdominal pressure in the standing position after instillation of peritoneal fluid. We report, here, a patient with COPD who had marked distress while on CAPD but was more comfortable with supine intermittent peritoneal dialysis. It is probable that the continuous high intraperitoneal pressure during CAPD caused diaphragmatic fatigue. During intermittent peritoneal dialysis, the supine position induces the least increase in intraperitoneal pressure; it may be the preferred mode of peritoneal dialysis for patients with COPD. PMID- 7999810 TI - The effect of in vivo erythropoietin on cytokine mRNA in CAPD patients. AB - There is increasing evidence that erythropoietin (EPO) affects immune function in addition to its well-known effects on the erythrogenesis. However, many of the studies examining the immunomodulatory capacity of this hormone have been in vitro. We examined mRNA signal for three important cytokines, interleukin 1(IL 1), interleukin 6 (IL-6), and tumor necrosis factor alpha (TNF-alpha), in stable continuous ambulatory peritoneal dialysis (CAPD) patients at baseline, and again at 2, 4, and 6 months after treatment with EPO. Significant changes were noted in all three cytokine mRNA signals in the majority of patients treated with this hormone. We conclude that EPO has significant immunomodulatory effects in vivo as defined by changes in cytokine mRNA compared to control. The significance of these changes, and their relationship to well-being and altered immune function remain to be better defined. PMID- 7999811 TI - Improved response to erythropoietin in peritoneal dialysis patients as compared to hemodialysis patients: role of iron deficiency. AB - Various studies have shown that peritoneal dialysis patients may require less erythropoietin (rHuEPO) than maintenance hemodialysis patients. Iron deficiency in hemodialysis patients may contribute to the difference in response. This study compares the response to rHuEPO in 24 patients on CAPD to 33 patients on hemodialysis. All the hemodialysis patients received intravenous iron to prevent iron deficiency. Peritoneal dialysis patients received rHuEPO subcutaneously twice weekly. Erythropoietin was administered intravenously thrice weekly in hemodialysis patients. In peritoneal dialysis patients, hematocrit was 23.1% and 30.1%, rHuEPO dose was 80.9 and 89.0 u/kg/wk, while in hemodialysis patients hematocrit was 22.2% and 31.2%, and rHuEPO dosage was 140.2 and 154.3 u/kg/wk at initiation, and six months after therapy (p < 0.05 for dose, hemodialysis vs CAPD). Serum iron and transferrin saturation remained normal both in peritoneal and hemodialysis patients. These findings suggest that hemodialysis patients require a higher dosage of rHuEPO than peritoneal dialysis patients for a comparable rise in hematocrit, even when iron deficiency is prevented with parenteral iron. The improved efficacy of rHuEPO in CAPD patients may be due to the better removal of the inhibitors of erythropoiesis and/or the subcutaneous route of administration. PMID- 7999812 TI - Initial intraperitoneal therapy for CAPD peritonitis: the Network 9 Peritonitis Study. AB - The choice of initial antibiotic therapy for continuous ambulatory peritoneal dialysis (CAPD) peritonitis is complex. To test the hypothesis that the initial choice of intraperitoneal antibiotics does not influence the outcome of therapy for CAPD peritonitis, we studied 1930 patients on peritoneal dialysis as of 1 January 1991, and recorded all episodes of peritonitis for one year. There were 1168 episodes of peritonitis for which 64% of the patients received intraperitoneal antibiotics as the first course of treatment. We determined peritonitis resolution, technique failure, hospitalization, and catheter removal rates as measures of successful treatment for peritonitis. Cephalothin, cefazolin, vancomycin, and ceftazidime were used alone or in combination with the aminoglycosides, tobramycin and gentamicin. The mean resolution rate was 65% following the first course of antibiotics and 76% by the third course of antibiotics, if necessary. The antibiotic regimens were not different with respect to resolution rate except when aminoglycosides were used alone. Technique failure was also greater in patients treated with aminoglycosides without other antibiotics. Hospitalizations were increased in patients treated with single drug therapy. If initial intraperitoneal therapy includes treatment for both gram positive and gram-negative bacteria, the initial choice of intraperitoneal antibiotics does not influence the outcome of therapy for CAPD peritonitis. PMID- 7999814 TI - Low incidence of peritonitis with the T-set. AB - Peritonitis is still one of the most important complications of peritoneal dialysis. Over the last few years, many efforts have been made in developing new device systems. A remarkable improvement has been obtained by modifying the original connection between the catheter and the bag, especially after the introduction of the Y-set. The aim of this study was to verify whether the use of a new device system, called the T-set, could reduce the incidence of peritonitis. This connector adds the advantages of the Y-set to those of the twin bag. In a group of 53 patients enrolled in a three-year period with a follow-up of 797 patient-months, we observed an incidence of peritonitis of one episode every 50 months. Furthermore, in the subgroup of 39 new patients, we observed an incidence of peritonitis of one episode every 89 patient-months. This new device can be a further step in the evolution of connectors that reduce the incidence of peritonitis. PMID- 7999813 TI - Is monotherapy with cefazolin or ofloxacin an adequate treatment for peritonitis in CAPD patients? AB - This prospective randomized study is an evaluation of efficacy of cefazolin and ofloxacin in 23 end-stage renal disease (ESRD) patients treated with continuous ambulatory peritoneal dialysis (CAPD) who experienced 38 episodes of peritonitis (P). Cefazolin was administered intraperitoneally: 1000 mg as loading dose and 250 mg every exchange as maintenance dose for ten days. Ofloxacin was given orally: first 300 mg, followed by ten daily doses of 200 mg. Microbes most frequently isolated from peritoneal effluent were Staphylococci (coagulase negative in 55.3%, aureus in 7.9%), Acinetobacter (in 5.3%), Klebsiella (in 5.5%), and Micrococcus (in 5.3%). Used as monotherapy, we found the efficacy of both cefazolin and ofloxacin inadequate for treatment of P in CAPD patients (cefazolin 65%, ofloxacin 67%) (NS). PMID- 7999815 TI - Peritonitis incidence on a disconnect CAPD-system with or without the use of iodine clamp shields. AB - The purpose of the study was to review a single center's experience with the disconnect system for continuous ambulatory peritoneal dialysis (CAPD), and to evaluate peritonitis incidence with and without use of iodine-containing clamp shields. The retrospective review of patients using the disconnect system lasted from January 1991 throughout March 1993, evaluating the peritonitis incidence with and without use of iodine clamp shields. In the observation period, a total of 103 patients were evaluated. Of these, 42 patients were treated with iodine clamp shields until July 1992 and then were instructed not to use the iodine clamp shields, thus acting as their own controls. We found an overall peritonitis incidence of 0.411 episodes/patient/year (= 29.2 patient-months/episode) on disconnect CAPD-system (Baxter), in spite of the fact that more than 60% of our dialysis population is treated with peritoneal dialysis. We found no difference in peritonitis rates with or without the use of iodine clamp shields. Peritonitis rates with clamp shields were 0.400 episodes/patient/year and, without clamp shields, were 0.400 episodes/patient/year. The introduction of a disconnect system provided a system with low incidence of peritonitis. No difference in peritonitis rates was observed with or without the use of iodine clamp shields, allowing us to reduce the cost of treatment and to simplify training procedures. PMID- 7999816 TI - Carrier-status for nasal staphylococci does not predict infections in CAPD patients. AB - It has been reported that nasal carriage of staphylococci may contribute to infections of the continuous ambulatory peritoneal dialysis (CAPD) catheter exit site or cause peritonitis due to this pathogen. Recently, a nasal ointment to eradicate these bacteria in patients and staff has been marketed with the implication that this treatment may reduce infection rates. In this study, we investigated 37 patients treated with CAPD for a mean of 38.8 +/- 6.4 months. Presence of nasal carriage of staphylococci was assessed using standard nasal swab techniques and related to bacteria identified at the time of previous infections. Results were analyzed using Spearman rank order correlation and linear regression analysis. In 119.5 patient years at risk, 50 infections with staphylococci (24 episodes of peritonitis and 26 exit-site infections) were evaluated. Nineteen patients were carriers of S. aureus or S. epidermidis; 6 patients were carrying both species. There was no correlation of current nasal carriage of staphylococci with previous infection. Although 23 of 37 patients were carriers, 14 of these never had infections due to nasal staphylococci. Only in 14 of 50 infections were bacteria species the same in the nose and at the site of infection. We conclude that prospective trials demonstrating a reduction of CAPD-related infections are needed before general use of prophylactic nasal antibiotic treatment can be recommended in these patients. PMID- 7999817 TI - Lack of correlation between nasal cultures positive for Staphylococcus aureus and the development of S. aureus exit-site infections: results unaffected by routine mupirocin treatment of nasal S. aureus carriage. AB - Whether nasal carriage of Staphylococcus aureus is associated with an increased risk of S. aureus exit-site infection remains controversial. We performed nasal cultures prior to peritoneal dialysis catheter placement in all of our patients beginning in September 1990. We also performed nasal cultures on a cohort of patients already on peritoneal dialysis. Patients with positive cultures received a prescription for a ten-day course of intranasal mupirocin. Exit-site and nasal cultures were performed on every subsequent office visit until the end of the study in April 1993. The initial visit and three widely-spaced subsequent visits were chosen for data analysis. There were 68 patients entered into the study. Data from a total of 272 visits were analyzed. The patients ranged in age from 18 80 years. There were 27 diabetics. We found no correlation between initial positive nasal cultures and the subsequent development of a S. aureus exit-site infection. All identified nasal carriers were treated with mupirocin. However, the subsequent development of a S. aureus exit-site infection could not be correlated to a prior S. aureus carrier state or lack thereof. PMID- 7999819 TI - Isolation of organisms in CAPD peritonitis: a comparison of two techniques. AB - The identification of organisms is important in the treatment of continuous ambulatory peritoneal dialysis (CAPD) peritonitis. We compared two techniques for isolating organisms in CAPD peritonitis. Clinical and microbiologic data on all episodes of peritonitis from 1991-1993 were prospectively recorded. The isolation of organisms from 77 episodes of peritonitis was done using the conventional centrifugation culture method from 1991-1992; the isolation of organisms from 121 episodes of peritonitis was done using the BACTEC method from 1992-1993. The total culture-positive rates were 75% for the BACTEC technique and 58% for the conventional technique (p = 0.05), with a higher isolation rate for gram-negative organisms (36% vs 18%, p < 0.05). In the isolation of organisms from new episodes of peritonitis, the culture-positive rates were significantly higher for the BACTEC than for the conventional technique (82% vs 55%, p < 0.01). The recovery rates of organisms for both techniques were similar for relapse peritonitis. The treatment outcomes of CAPD peritonitis for the two technique groups, and for the culture-positive and culture-negative groups were not significantly different. In conclusion, the BACTEC method yielded a higher rate of positive cultures for CAPD peritonitis, but did not affect treatment outcome of the infections. PMID- 7999818 TI - Staphylococcus aureus CAPD-related infections are associated with nasal carriage. AB - Staphylococcus aureus nasal carriage has been shown to be associated with an increased risk of S. aureus exit-site infections, but its association with peritonitis is less well established. We performed a four-year prospective study to determine the relationship between S. aureus continuous ambulatory peritoneal dialysis (CAPD)-related infections and nasal carriage. All patients who had been started on CAPD from 1989 to 1992 had regular nose cultures. S. aureus nasal carriage was defined as two of three positive nose cultures. A total of 41 carriers and 105 noncarriers were studied. The rates of S. aureus exit-site infection (0.23 vs 0.09 episode/patient/year, p < 0.005), peritonitis (0.33 vs 0.10 episode/patient/year, p < 0.005), and catheter loss (0.12 vs 0.05, p < 0.01) were significantly higher among the carriers. Life-table analysis showed a significant risk of S. aureus exit-site infection and peritonitis for carriers (p < 0.01). Logistic regression analysis showed that S. aureus nasal carriage was the most important predictive factor for S. aureus peritonitis. In conclusion, our study showed that S. aureus nasal carriage is related to an increased incidence of S. aureus CAPD-related infections. PMID- 7999821 TI - Culture-negative CAPD peritonitis: the Network 9 Study. AB - A portion of peritonitis episodes are reported as culture-negative or as initial no growth peritonitis (INGP). To determine if demographics, symptoms, signs, treatment, and outcome were different in INGP when compared to culture-positive peritonitis (Pos), we examined data from the Network 9 Peritonitis and Catheter Survival Study. Only peritonitis episodes occurring in adults with peritoneal dialysis (PD) fluid WBC counts greater than 100 were included in the analysis. INGP accounted for 14% of the episodes of peritonitis. Organisms grew out of 13 of the 37 patients in INGP that were recultured: 3 fungal, 5 gram-negative, and 5 gram-positive isolates. A difference in culture methodology for the two groups could not be detected. There was no difference in gender, race, incidence of diabetes, previous peritonitis, or exit-site infections between the two groups. INGP had a greater percentage of patients over age 70 (23.3% vs 14.7%, p < 0.05), and a larger percentage of INGP patients placed additives in their dialysate (55% vs 43.6%, p < 0.05). There was no difference in symptoms or signs between the two groups. The INGP group had half the catheter removal rate (9/103 vs 110/630 for Pos, p < 0.05), otherwise, there was no difference in the rate of hospitalization, death, or switch to hemodialysis. There was no difference in types of drugs used or method of drug administration between the two groups. A lower percentage of INGP patients were treated for 6 days or less and a higher percentage received 7-10 days of intraperitoneal (IP) therapy when compared to Pos.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7999820 TI - Fungal peritonitis in peritoneal dialysis: critical review of six cases. AB - Fungal peritonitis (FP) is uncommon in patients on peritoneal dialysis (PD); it is difficult to treat and has a high mortality rate. We report 6 cases of fungal peritonitis observed between 1980 and 1992 in our center. The etiologic agents were: Candida spp., C. guilliermondi, C. parapsilosis, C. albicans, and Verticillium spp. All 6 patients had suffered at least one episode of bacterial peritonitis in the two months before the fungal infection appeared and were all treated by intraperitoneal administration of antibiotics. The catheter was removed early in 3 patients followed by antimycotic therapy, while the remaining 3 patients received antimycotic therapy, with removal of the catheter in a later stage. The result in the first group was that they all switched permanently to hemodialysis, while in the second group there were 2 deaths and 1 transfer to hemodialysis. In the light of these 6 cases, we analyzed 22 published reports to assess risk factors, therapy, and outcome of this pathology. The major predisposing factors were intraperitoneal antibiotics and bacterial peritonitis, and the best results were obtained by continuing PD plus intraperitoneal and systemic antifungal agents. PMID- 7999822 TI - Phosphate binders do not reduce bioavailability of oral cefuroxime-axetil in patients on peritoneal dialysis treatment. AB - Cefuroxime is a second-generation cephalosporin that can be used for the treatment of peritoneal dialysis-related peritonitis. Cefuroxime-axetil is an orally available pro-drug of cefuroxime. The effect of concomitant use of a phosphate binder on the bioavailability of cefuroxime-axetil was studied in 7 continuous ambulatory peritoneal dialysis (CAPD) patients who had not recently suffered from peritonitis. On two occasions, we measured cefuroxime levels in plasma, peritoneal effluent, and urine for 24 h after the ingestion of 1 g of cefuroxime-axetil: once together with a phosphate binder (+PB) and once without ( PB). Peak plasma concentrations (Cmax) were +PB: 22.7 mg/L (15.3-32.6) (median and range) and -PB: 23.2 mg/L (18.9-27.4). The area under the curve (AUC) of the plasma levels was +PB: 364 mg h/L (247-530) and -PB: 368 mg h/L (296-438). The plasma elimination half-life (t1/2) was +PB: 13.9 h (11.5-14.6) and -PB: 13.8 h (12.2-15.4). Cefuroxime concentrations in the peritoneal effluent from the first exchange were 1.9 mg/L (0.5-6.2) (+PB) and 3.4 mg/L (2.1-4.7) (-PB). In the peritoneal effluent from the second up to the last exchange, the cefuroxime levels were stable at +PB: 5.0 mg/L (2.0-8.8) and -PB: 5.3 mg/L (1.8-7.5). The total amount of cefuroxime excreted into peritoneal effluent and urine was +PB: 82 mg (30-124), -PB: 100 mg (36-129). So Cmax, AUC, t1/2 and the total amount of excreted cefuroxime were not different. Therefore, the bioavailability of cefuroxime-axetil is not reduced by the use of a phosphate binder. PMID- 7999823 TI - The differential activity of aminoglycoside antibiotics with rifampin explored in a kinetic in vitro model of implant-associated infection (Staphylococcus epidermidis). AB - Implant-associated infections offer resistance to antibiotic treatment and possibly do so because the causative bacteria which reside on the artificial surface are enclosed in a protective matrix (biofilm) shielding the bacteria against the action of host defenses and antibiotic action. We have investigated in vitro the effect of various antimicrobial agents on biofilms of Staphylococcus epidermidis, which is the main organism responsible for implant-associated infections. Rifampin was found to exert superior activity, albeit incomplete, against S. epidermidis biofilms using an assay system which enabled the determination of the kinetics of antibiotic action over five days. In a large screening study looking for agents capable of completing the action of rifampin, gentamicin was unexpectedly found to be antagonistic to rifampin. The present study was undertaken to investigate further the activity of gentamicin and five other aminoglycoside antibiotics using a wider range of concentrations (2.5-20 micrograms/mL). The main findings were a marked synergy with rifampin demonstrated by streptomycin, producing a bactericidal outcome, which contrasted sharply with the indifference or antagonism shown by the other aminoglycosides. We then studied in further detail the effect of separate combinations of streptomycin and gentamicin with rifampin over a wider concentration range of each agent (1.25-40 micrograms/mL). Streptomycin showed strong rapid synergy with rifampin even at the lowest concentration of each antibiotic. Gentamicin demonstrated a concentration-related antagonism towards rifampin which was independent of rifampin concentration. The data support the conclusion that streptomycin, like cell-wall active antibiotics, exerts a potent synergy with rifampin against S. epidermidis biofilms, and that the other aminoglycosides, predominantly gentamicin, strongly antagonize rifampin action.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7999824 TI - Time-kill efficacy of antibiotics in combination with rifampin against Staphylococcus epidermidis biofilms. AB - Infections associated with implants are frequently resistant to conventional antibiotic therapy. This resistance has been ascribed to the presence of bacteria on the artificial surface within a protective glue-like matrix forming a bacterial biofilm. We have demonstrated that experimental biofilms of Staphylococcus epidermidis, the main pathogen associated with implantation, are exquisitely sensitive to the action of rifampin. This effect of rifampin is incomplete, however, with the emergence of rifampin-resistant survivors that readily repopulate the biofilm. Studies were therefore performed to determine the effect of combinations of 13 different antibiotics with rifampin against standardized S. epidermidis biofilm preparations in an in vitro assay enabling the kinetic measurement of antibiotic action over a five-day period. The antibiotic combinations with rifampin demonstrated unsuspected divergent patterns of antimicrobial activity against the biofilms: 1. rapid synergy with rifampin was observed with cell-wall active antibiotics (cloxacillin, cephalothin, cefazolin, and cefamandole), whereas slower synergy occurred with vancomycin, ciprofloxacin, tetracycline, and amikacin; 2. some antibiotics (tobramycin, erythromycin, clindamycin, fusidic acid) did not influence the outcome; 3. gentamicin unexpectedly showed marked antagonism to rifampin. These results are relevant to the design of optimal therapeutic regimens for the management of resistant implant-associated infections. PMID- 7999825 TI - Computer interaction: peritonitis. PMID- 7999826 TI - Silver peritoneal catheters reduce bacterial colonization. AB - Bacterial colonization potentials by Staphylococcus aureus (Staph. aureus) were determined in silver peritoneal dialysis (PD) catheter materials and were compared to colonization of the same bacteria in silastic catheter materials. The bacteria were colonized in two different experimental systems: In Vitro: In an in vitro biofilm bacterial culture system with a modified Robbins' device (MRD), seven different clinical strains of Staph. aureus were grown in PD effluents on silver or silastic catheter discs, each 0.5 cm in diameter. In identical experimental conditions, reduced bacterial growth was detected in silver catheter discs compared to growth on silastic discs, but the results were not statistically different (p = 0.12). In Vivo: In a rabbit model of PD the, in vivo colonization potential of Staph. aureus was examined in two groups of rabbits using silver (n = 3) and silastic (n = 3) PD catheters. The exit sites of the PD catheters were inoculated with a single strain of Staph. aureus for six days, followed by PD for six days. The rabbits were then sacrificed. After sacrifice, comparison between the bacterial counts of identical segments of silver and silastic catheters showed that there had been a reduction in the growth of Staph. aureus in vivo on silver PD catheters, contrary to the increased growth on the silastic catheters (p < 0.05). Reduced bacterial growth on the silver PD catheters in vivo indicates that the release of silver in tissues over time cause antibacterial effects in vivo. Further in vivo experiments are needed before future clinical use of silver catheters in PD patients. PMID- 7999827 TI - Moncrief's technique for peritoneal catheter placement: experience of a CAPD unit. AB - A decrease in the peritonitis rate and the incidence of catheter exit-site/tunnel (E/T) infection are the most important factors affecting the permanent peritoneal catheter in continuous ambulatory peritoneal dialysis (CAPD) patients. Moncrief et al. have introduced a novel methodology (two phases) for peritoneal catheter placement (7.8). The most relevant characteristic is that the external portion remains buried on the subcutaneous tissue (sterile environment) during the healing process. After four to six weeks, the catheter is brought out through a small incision (0.5 cm) distal 2 cm from the subcutaneous cuff, and peritoneal dialysis may be initiated. The data available, presented by Moncrief et al., show a lower incidence of peritonitis rate and E/T infection with this implantation technique, when compared with a classic technique. The aim of this study is to learn if the placement of a peritoneal catheter with Moncrief's methodology decreases the incidence of complications related to peritoneal catheters. We treated 29 patients (group C) with the conventional procedure and 25 patients (group M) with the Moncrief technique. Follow-up was similar for both groups (C = 12.2 +/- 7.9 months vs M = 11.1 +/- 6.1 months, NS). The time buried was 3.23 +/- 0.9 weeks (2-5). Eleven patients completed four weeks with the catheter buried subcutaneously (group M-4). The incidence of E/T infection was similar for groups C and M, and lower in group M-4 (p < 0.05). The number of catheters free of infection was less in group C (31%) than in group M (46%) and M-4 (67%) (p < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7999828 TI - Comparison of Swan neck catheter with Tenckhoff catheter for CAPD. AB - To decrease the incidence of exit-site infection, the Swan neck catheter has been used since 1991. Twenty-six patients received Swan neck catheter implants over the past three years. Fifteen patients suffered from exit-site infections and 2 of them developed tunnel infections. The incidence of exit-site or tunnel infections in the Swan neck group revealed no difference from those patients receiving Tenckhoff tube implants (n = 154). Two patients in the Swan neck group and 8 in the Tenckhoff group had tube migrations. There was no difference between the two groups. No patient in the Swan neck group suffered from cuff extrusion or pericatheter leakage, while 9 in the Tenckhoff group suffered from cuff extrusions and 5 had pericatheter leakages. The cumulative catheter survival rates at one, two, and three years in the Swan neck group were 90.9%, 80.2%, and 67.9%, while those in the Tenckhoff group were 84.7%, 67.9%, and 54%. We conclude that the patients receiving Swan neck catheter implantations had a lower incidence of cuff extrusion and pericatheter leakage, and better catheter survival, though the incidence of exit-site/tunnel infection and tube migration was no better than in the Tenckhoff catheter group. PMID- 7999829 TI - Complications of permanent catheter implantation for peritoneal dialysis: incidence and risk factors. AB - We reviewed the incidence and risk factors for complications after insertion of permanent catheters for peritoneal dialysis (PD). We implanted 192 peritoneal catheters in 137 patients over ten years. Fifty-three complications were observed in 50 catheters (27.6%) implanted in 42 patients (30.6%): malposition or omental entrapment (13%), dialysate leak (8.9%), hemoperitoneum (3.6%), peritonitis (1%), surgical wound infection (0.5%), and chylous ascites (0.5%). The only significant risk factors for a complicated insertion were previous abdominal surgery, particularly if it affected the peritoneal membrane, and early use of the catheter after implantation (< 5 days), independent of surgical or closed insertion. PMID- 7999830 TI - Simultaneous catheter replacement-removal during infectious complications in peritoneal dialysis. AB - The aim of this study was to verify whether the replacement of the peritoneal catheter in a single operation and during infectious complications of peritoneal dialysis is effective and safe. Sixty-eight infectious complications refractory to appropriate antibiotic therapy were treated by this technique: 26 tunnel infections, 22 peritonitis-complicating tunnel infections, 12 refractory peritonitis, and 8 recurrent peritonitis. Operations were successful in all cases of tunnel infection and recurring peritonitis, and in all cases but one of peritonitis-complicating tunnel infection. Ten failures occurred among the 12 catheters removed for refractory peritonitis. Microorganisms cultured in these 10 failures were: Fungi (3 cases), Mycobacterium (2 cases), Pseudomonas (2 cases), Acinetobacter (1 case), Acinetobacter+Pseudomonas (1 case), and Enterococcus (1 case). Complications were 3 one-way obstructions and 2 external dialysate leaks. This study supports the simultaneous catheter replacement-removal procedure during infectious complications of peritoneal dialysis (PD) with the exception of refractory peritonitis; this technique spares the patient the temporary vascular access, the shift to hemodialysis, and a second operation to insert a new catheter. There are few complications. PMID- 7999831 TI - PD-related infections of standard and different disconnect systems. AB - A review of 332 patients initiating continuous ambulatory peritoneal dialysis (CAPD) treatment from January 1988 throughout September 1993, with a total observation time of 5237 patient-months. Seven peritoneal dialysis (PD) systems were used, three of which were comparable regarding patient characteristics: standard system (Baxter) and two disconnect systems, Twinbag (Baxter) and Gemini (Gambro). The two disconnect systems were identical in principle, except that Twinbag used iodine as disinfectant of connections and Gemini used alcohol as disinfectant. We found a reduction of peritonitis rates in one of the disconnect systems--Twinbag (iodine) 0.42 episodes/patient/year--and a slight increase in another disconnect system--Gemini (alcohol) 1.17 epi/patient/yr--compared to standard system (iodine) 0.92 epi/patient/yr. An improvement of exit-site infections (ESI) and tunnel infections was seen in both disconnect systems (0.17 and 0.20 epi/patient/yr) compared to standard system (0.35 epi/patient/yr). Introduction of disconnect CAPD system reduced peritonitis rates in systems using iodine as disinfectant. Disconnect systems reduced ESI, probably due to less trauma to the catheter. We recommend the use of disconnect CAPD systems using iodine instead of alcohol as disinfectant. PMID- 7999832 TI - High flow peritoneal dialysis. AB - We have developed a catheter extension/continuous ambulatory peritoneal dialysis (CAPD) set (ANDY high flow set) of larger lumen (minimum internal diameter 3.25 mm), and compared peritoneal dialysate flow rates in two groups of 6 stable CAPD patients of comparable age, sex distribution, and time on dialysis according to type of catheter. Both groups were studied with two different extension/sets, standard ANDY and ANDY high flow set. The shortest infusion time was observed with the combination Cruz catheter/ANDY high flow set. The switch to a high flow set decreased significantly the inflow time of both types of catheter, and the infusion time of the Tenckhoff catheter/ANDY high flow combination approximated that of the Cruz/ANDY combination. Likewise, the dialysate outflow rates were highest with the Cruz catheter/ANDY high flow set than with any other catheter/set combination (p = 0.005). This was apparent, not only in the total outflow time, but also in the vol/min during the first 4 min (p = 0.005). None of the patients experienced discomfort during the dialysis exchanges with the high flow system. This combination of Cruz catheter/high flow set effectively reduces the dialysis exchange time and is very much appreciated by the patients. PMID- 7999833 TI - Computer interaction: instructions to home dialysis patients regarding disposal of peritoneal dialysis waste. PMID- 7999834 TI - In vitro influence of lactate on function of peritoneal fibroblasts. AB - The authors studied the effect of sodium lactate (NaLact) on the function of human peritoneal fibroblasts (F) in vitro. NaLact inhibits the proliferation of fibroblasts in a dose-dependent way: at a concentration of 40 mM, it decreases the growth of these cells by 34%. A similar effect was observed with other solutes (glucose, mannitol, sodium chloride) at identical concentrations, suggesting that the factor responsible for slower growth of the cells was hyperosmolality. When applied to fibroblast monolayers, NaLact (40 mM) increased the synthesis of total proteins by 10%. Exposure of the fibroblasts to NaLact did not increase noncollagen protein production, and the observed increase in total protein synthesis was due to the increased synthesis of collagen. We could not reproduce this effect of lactate on fibroblast collagen synthesis with other osmotic solutes. Our results suggest that dialysis fluid hyperosmolality may be one of the factors responsible for the decrease of the cellular components within the peritoneal interstitium; whereas NaLact is specifically responsible for the increased production of collagen by peritoneal fibroblasts, leading to the deposition of masses of collagen in the extracellular space. PMID- 7999835 TI - Effect of the dialysate effluent from CAPD patients on peritoneal mesothelial cells and fibroblasts. AB - The authors studied the in vitro effect of overnight "dwelled" dialysate obtained from 5 continuous ambulatory peritoneal dialysis (CAPD) patients on the growth of, and protein synthesis by, peritoneal mesothelial cells and fibroblasts. In each patient, an overnight exchange was performed with Dianeal 2.5% on day 1 and with a solution containing amino acids 1.1% on day 2. Both types of dialysate supported the proliferation of fibroblasts and mesothelial cells, but the amino acid dialysate had a stronger effect on the growth of mesothelial cells than the Dianeal dialysate did. In the presence of either dialysate, synthesis of noncollagen proteins by mesothelial cells and fibroblasts was low. By contrast, the synthesis of collagen was enhanced, and the Dianeal dialysate had a much stronger effect than the amino acid dialysate did. Present results show that, during its intraperitoneal dwell, dialysis fluid within the peritoneal cavity stimulates the generation of bioactive substances which affect the function of peritoneal cells. This reaction is influenced by the composition of the dialysis solution. PMID- 7999836 TI - Dialysis solutions buffered with lactate or bicarbonate: in vitro comparison of two dialysis solutions on human peritoneal cell growth from ESRD and non-ESRD patients. AB - In order to evaluate the injury to the mesothelial cell layer during long-term peritoneal dialysis (PD), a dialysis solution (solution A), buffered with bicarbonate, stabilized with 10 mmol/L glycylglycine, and sterilized by filtration (0.22 micron double filtration, pH = 7.4), was compared to traditional heat sterilized lactate solution (solution B) on human mesothelial cell cultures. The respective effects of both solutions were evaluated on first passage cells by 3H thymidine incorporation after 72-, 96-, 120-, and 144-h contact. Mesothelial cells to be cultured were obtained from the omentum biopsies of 7 end-stage renal disease (ESRD) patients (during first peritoneal catheter placement) and from 7 non-ESRD patients undergoing abdominal surgery. Solution A (diluted 1/5) induced a time-dependent stimulation of growth in 6 cases of ESRD patient cell cultures, and inhibition occurred only in 1 case. Stimulation was also observed in 5 non ESRD patient cell cultures, and no effect occurred in 2 cases. Solution B inhibited growth in all the cultures except in 1 case of an ESRD patient in which no effect was observed. This study shows that solution A induced mesothelial cell proliferation, while an inhibitory effect of solution B was observed. No significant differences were observed between the sensitivity of mesothelial cells from ESRD and non-ESRD patients. Further analysis will be carried out to identify precisely the cause of the differences observed: buffer or glycylglycine by themselves and/or glucose by-products. PMID- 7999837 TI - In vitro compatibility of a 1.1% amino acid containing peritoneal dialysis fluid with phagocyte function. AB - The effects of a recently introduced peritoneal dialysis fluid (PDF) containing amino acids (AA) were compared with those of a glucose-based PDF (G-PDF) on viability and function of donor granulocytes (PMNs) in vitro. After 30 min incubation in the PDF, viability, assessed by trypan blue exclusion, and phagocytosis capacity (PC), tested in two assays using a fluorescein and a 3H labeled Staphylococcus epidermidis strain, were significantly better in AA-PDF than in G-PDF (p < 0.002 in the 3H-assay). Bactericidal activity was not different in the PDFs. If pH of G-PDF was adjusted from 5.2 to neutral, differences in PC disappeared. In AA-PDF, PMN chemiluminescence (CL) response was significantly higher than in G-PDF (p < 0.003). At neutral pH, however, PMNs showed a significant stronger CL-response in 1.36% G-PDF than in AA-PDF (p < 0.05). These data suggest that this AA-PDF has little detrimental effect on phagocyte viability and function. The improved compatibility over G-PDF in in vitro tests seems to be pH dependent. The reduced chemiluminescence response compared to 1.36% G-PDF with neutral pH is possibly due to quenching by (one of the) amino acids and osmolarity. PMID- 7999838 TI - Biocompatibility studies with bicarbonate-based solutions. AB - During long-term peritoneal dialysis (PD) treatment, the biocompatibility of the dialysis fluid is one of the factors that determine the functional integrity of the peritoneal mesothelium and stroma, and the alertness and functional capacity of the peritoneal host defense system. In vitro studies show that conventional acidic lactate-based PD solutions (LB fluids) are detrimental to some of the more important functions of the peritoneal cell system including mesothelial and white blood cells. The main toxic components of the fluids are the high hydrogen ion content (pH = 5-5.6), high lactate concentration, and osmolality. Some toxic side effects can be omitted using bicarbonate-based fluids (BB fluids), in which lactate has been replaced by bicarbonate and the pH has been normalized (7.2 7.4). The present paper is an overview of the biocompatibility tests and studies performed using bicarbonate-based continuous ambulatory peritoneal dialysis (CAPD) fluids. While the final long-term clinical evaluation of the BB fluids is still missing, biocompatibility tests indicate that these fluids are less toxic to many cell systems than the conventional acidic LB fluids. BB fluids with a high glucose content remain cytotoxic. The BB fluids are well tolerated in animal studies. Some BB fluids increase the ultrafiltration in short-term animal studies when compared with LB fluids. The few animal studies failed to demonstrate a better preservation of the peritoneal membrane integrity by BB fluids. The difference in cell toxicity between LB and BB fluids as measured in vitro also seems detectable during the first 30 min of intraperitoneal dwell in man. PMID- 7999839 TI - Effects on the peritoneal membrane of rabbits of a single bicarbonate solution containing glycylglycine. AB - So far, no one has devised ideal, on-line mixed bicarbonate solutions for hemodialysis and continuous ambulatory peritoneal dialysis (CAPD) because current preparations can lead to precipitation of calcium and magnesium carbonate during treatment. The author has prepared a new, single bicarbonate dialysis solution that contains glycylglycine (BiGG). With a bicarbonate/glycylglycine ratio of 30/10 mM/L, this solution has a stable pH of 7.35; sterilized through a 0.22 micron filter, it remains stable for over 15 months when stored at 10 degrees-40 degrees C. When infused (40 mL/kg bw) in rabbits daily for 25 days, the BiGG solution showed excellent peritoneal-membrane tolerance and biocompatibility. Comparative ultrafiltration (UF) studies with BiGG and standard lactate (La) solutions in rabbits showed that net UF with La solution peaked at 2 h and decreased significantly at 4 h and 6 h. Net UF with BiGG solution peaked at 4 h and was sustained at 6 h; in all instance it was greater than that of La solution by approximately 15%, 30%, and 40% at 2, 4, and 6 h, respectively. During the initial 2-h dwell period, the pH of La solution increased from an initial 5.5 to 7.18, whereas that of the BiGG solution remained stable at 7.35. In all rabbits, the peritoneal fluid contained phosphatidylcholine at all times. However, its concentration was significantly higher in animals receiving the BiGG solution than in those receiving the La solution. The author concludes that this new single BiGG PD solution is simple to use, stable, and of a normal pH.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7999840 TI - Pulse oral calcitriol to treat hyperparathyroidism in 43 CAPD patients. AB - To further study the effect of pulse oral calcitriol on the level of intact parathyroid hormone (iPTH), we have studied the response of 43 patients treated with 5.0 mcg calcitriol bi-weekly for one year. Mean iPTH decreased from 603 pg/mL +/- 262 (+/- SD) to 222 pg/mL +/- 185 (p < 0.001). Thirty-six patients responded showing a decrease in iPTH from baseline; 7 patients showed no decrease in iPTH. Transient hypercalcemia (calcium > 10.5 mg/dL) was noted in 6 patients of the responder group which corrected with temporary discontinuation of pulse therapy. Pulse oral calcitriol is an effective therapy to decrease elevated iPTH levels in continuous ambulatory peritoneal dialysis (CAPD) patients with hyperparathyroidism. PMID- 7999841 TI - Single-dose oral calcitriol and changes of plasma 1,84iPTH in uremic children. AB - Both intravenous and oral 1,25(OH)2 D3 pulse therapy are effective in decreasing iPTH in patients with chronic renal failure. In order to understand why intermittent application of calcitriol is effective, we investigated 10 children with advanced renal failure (4 female, 6 male; median age 6.5 [3-16] years; body surface area 0.58-1.57m2; CCR 7 [5-47] mL/min/1.73m2) with elevated baseline concentrations of 1,84iPTH (median 63.5 [9.4-300] pmol/L). After a standard dose of 2 micrograms calcitriol per os (equal to 1.27-3.45 micrograms/m2), serum 1,25(OH)2D3 concentrations increased. The peak concentration occurred after 6 h (3-12), and 1,25(OH)2D3 serum levels returned to baseline by 48 h. 1,84iPTH concentrations were significantly suppressed by 6-72 h. The median maximal decrease was 51.4% of baseline (22.3%-74%). The decrement was a function of baseline 1,84iPTH, but not of 1,25(OH)2D3 serum peak concentration, area under the curve, body surface area, or change in ionized serum calcium. We conclude: (i) oral 1,25(OH)2D3 has a prolonged (up to 72 h) suppressive effect on 1,84iPTH concentrations in uremic patients, and (ii) the wide interindividual variation in suppression of 1,84iPTH was not explained by the kinetics of 1,25(OH)2D3 concentration, which implies that additional factors influence the 1,84iPTH response to 1,25(OH)2D3. PMID- 7999842 TI - Long-term effect of oral calcitriol single weekly pulse in CAPD and in HD. AB - This study was undertaken to evaluate the long-term effect of single weekly oral pulse calcitriol therapy (0.05 mcg/kg) in 16 uremic patients. Eight (5 female, 3 male; aged 51.6 +/- 8.5 years) were on continuous ambulatory peritoneal dialysis (CAPD) for 28.8 +/- 12.7 months with basal intact parathyroid hormone (iPTH) 247 +/- 60 pg/mL. Eight (6 female, 2 male; aged 53 +/- 17.9 years) were on hemodialysis (HD) for 76.3 +/- 55 months with basal iPTH 270.9 +/- 92. Calcium dialysate was 1.75 mmol/L in all patients and serum phosphorus was controlled with CaCO3 2-4 g/day. Ca and P were measured weekly; iPTH and alkaline phosphatase were measured monthly. After two months, iPTH decreased to 132.4 +/- 89 (p < 0.05 vs basal values) in the HD patients and to 158.2 +/- 61 (p < 0.05) in the CAPD group. After six months, iPTH decreased to 108.6 +/- 73.2 (p < 0.01) in the HD patients and to 126.5 +/- 48 (p < 0.01) in the CAPD patients. Two patients (1 HD and 1 CAPD) who were not compliant with phosphate binder therapy were dropped. To control hyperphosphatemia in 1 HD patient we reduced bolus to 0.03 mcg/kg. Two CAPD patients presented hypercalcemia and required calcium dialysate of 1.25 mmol/L. In conclusion, single weekly oral pulse of calcitriol appears to be effective in suppressing mild hyperparathyroidism both in CAPD and in HD patients, even though some variations in the protocols may be required. PMID- 7999843 TI - Effective peritoneal blood flow (EPBF) and patient characteristics. AB - The aim of these studies was a comparison of effective peritoneal blood flow (EPBF) during intermittent peritoneal dialysis (IPD) in uremic patients with varying primary renal disease, sex, age, body weight, and IPD duration. EPBF was estimated by calculation of diffusive mass transfer coefficient (KBD) of carbon dioxide at 2.5 min dwell of 1.5% glucose dialysis solution (2 L). EPBF estimated during IPD in 21 patients was a mean of flow rates obtained in each patient at the beginning, in the middle, and at the end of 1-2 dialyses. Our results suggest that EPBF during IPD is not significantly dependent on primary renal disease, sex, age, and body weight, nor does it change during the first few months of IPD. PMID- 7999844 TI - Effects of calcitriol pulse therapy per os in CAPD patients. AB - Pulse calcitriol therapy (IV or per os) has been efficacious in hemodialysis (HD) patients to inhibit parathyroid hormone (PTH) levels, but there are very poor data for continuous ambulatory peritoneal dialysis (CAPD) patients. For this reason, we used calcitriol (C) per os (0.75-1.5 micrograms three times weekly) in 19/54 patients who had PTH > 150 pg/mL (on peritoneal dialytic treatment for 6 114 months, weekly KT/V 2.01 +/- 0.43); 16% were in therapy with calcium (Ca) carbonate, 26% with calcium acetate alone, and 58% with calcium acetate associated with magnesium (Mg) carbonate and reduction of dialysate Ca (CaD) and dialysate Mg (MgD), respectively, to 1.25 and 0.25 mmol/L. In 5 patients (26%), a further reduction of CaD to 0 mmol/L has been necessary, and 3 patients must be considered nonresponders after three months of treatment. In conclusion, the use of calcitriol as pulse therapy (three times weekly), and at low doses, allows a good control of secondary hyperparathyroidism in 85% of patients who are using phosphate binders without aluminum, if CaD is reduced in some patients to 1.25 or even to 0 mmol/L. PMID- 7999846 TI - Hyperhomocysteinemia as a possible role for atherosclerosis in CAPD patients. AB - It has been shown that hyperhomocysteinemia is a risk factor for atherosclerotic vascular disease. In this study, we measured total plasma homocysteine in continuous ambulatory peritoneal dialysis (CAPD) patients and evaluated its correlation with atherosclerosis. Subjects consisted of healthy volunteers, and hemodialysis (HD) and CAPD patients. Fluoro-HPLC was employed to estimate plasma levels of total homocysteine (Hcy). Plasma levels of total Hcy were significantly higher in the CAPD patients compared with the HD patients and controls. Atherosclerotic score (ASS) was calculated, and the correspondence with plasma levels of total Hcy was analyzed. There was a significant correlation between plasma levels of total Hcy and ASS in CAPD patients. However, plasma levels of total Hcy did not correlate with age, plasma vitamin B6 level, residual renal function, protein catabolic rate (PCR), or KT/V. Our present study suggests that elevated concentrations of total plasma Hcy might play a role in the development of atherosclerosis in CAPD patients. PMID- 7999845 TI - Growth hormone and cortisol secretion before and after erythropoietin therapy in CAPD patients. AB - Correction of anemia with recombinant human erythropoietin (rHuEPO) in patients with end-stage renal disease (ESRD) has been associated with improvement of several endocrine abnormalities. However, long-term effects of this therapy on pituitary secretion in patients undergoing continuous ambulatory peritoneal dialysis (CAPD) is not known. The aim of the present work was to assess the growth hormone (GH) and cortisol responses to insulin-induced hypoglycemia before and after the correction of anemia with rHuEPO therapy in CAPD patients. Five well-nourished and clinically stable patients were studied before and after 12-24 weeks of rHuEPO treatment. Seven normal volunteers were studied as controls. Insulin-induced hypoglycemia tests were performed prior to starting rHuEPO therapy and again after partial correction of anemia. Blood samples for GH, cortisol, and glucose were collected between -30 and 120 min after insulin (0.1 U/kg bw) administration. GH responses to hypoglycemic stress were characterized by marked differences in single patients when compared with the control group. However, the GH peak and the area under the secretory curves (AUC) of GH responses in CAPD patients (10.6 +/- 4.8 micrograms/L and 15.4 +/- 6.1 micrograms h/L, respectively) did not differ from those obtained in control subjects (14.3 +/- 4.1 micrograms/L and 19.4 +/- 3.5 micrograms h/L, respectively). The study, after correction of anemia, showed an evident decrease of GH values at each time point on the response curve in 4 patients, and no modification in 1 patient. Mean values of GH peak and AUC were 8.8 +/- 2.8 micrograms/L and 9.6 +/- 2.3 micrograms h/L.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7999847 TI - Continuous peritoneal dialysis in children with acute renal failure. AB - Continuous peritoneal dialysis (CPD) was performed in 13 children with acute renal failure (ARF) in our intensive care units (ICU). The median age was 6 months (range 3 days to 77 months). Sixty-nine percent of the patients (9/13) were below the age of 12 months. CPD was performed for a median duration of 5 days (range 1-35 days). In 62% of the patients (8/13), the cause of ARF was acute tubular necrosis (ATN) due to cardiac surgery. The outcome of CPD regarding total survival was 54% (7/13). A high mortality was registered (83% of the deaths [5/6]) within the first year of life, which suggests a worse prognosis if ARF occurs at this age. Half of the total deaths (3/6) were among the cardiac surgery patients. Peritoneal equilibration tests (PET) were performed utilizing measurement of urea and glucose transport through the peritoneal membrane at short intervals during a period of 45-60 min from the start of treatment. Short dwell times of 5-20 min were found to be sufficient for adequate uremic control until a satisfactory daily urine production was noted. CPD is a useful and simple treatment modality for ARF in critically ill ICU children. Equilibration tests are useful and should be considered for optimization of CPD treatment in critically ill children with ARF in order to achieve the goal of controlling uremia and fluid overload, and giving nutritional support. PMID- 7999848 TI - Hydrostatic intraperitoneal pressure in children on peritoneal dialysis: practical implications. An 18-month clinical experience. AB - Intraperitoneal pressure (IPP) is easy to measure routinely in children on peritoneal dialysis (PD) (especially with the twin bag Y-set) as described in adults: value expressed in centimeters of water, average of IPP (mean IPP) at inspiration and at expiration, with point zero located on the mid-axillary line while the patient rests in a perfectly supine position. IPP remained high during the first two to three days postsurgical peritoneal catheter implantation (15 +/- 4 cm) despite low dialysate volume per exchange (10 mL/kg). Afterwards, IPP decreased (10 +/- 2 cm) despite increasing dialysate volume from 10-50 mL/kg. Mean IPP seemed lower in infants (5 +/- 3 cm) in contrast to children (10 +/- 2 cm) on chronic PD with dialysate volume of 1000 mL/m2. There was a strong negative linear correlation between ultrafiltration (UF) volume and mean IPP with isotonic dialysate (1.36% dextrose concentration). By contrast, there was only a weak positive linear correlation between UF volume and mean IPP with hypertonic dialysate (3.86% dextrose concentration). PMID- 7999849 TI - The treatment of Staphylococcus aureus nasal carriage in pediatric peritoneal dialysis patients. AB - This study evaluates the dialysis-related infection rate in children receiving peritoneal dialysis with Staphylococcus aureus nasal carriage. Children with S. aureus nasal carriage were randomized to treatment with rifampin and bacitracin or no treatment. The children were observed for one month after randomization for evidence of a S. aureus dialysis-related infection. Individuals with nasal carriage had a higher incidence of S. aureus dialysis-related infection than those patients without carriage (p < 0.05). Those children treated for nasal carriage had a lower dialysis-related infection rate than those who were untreated (p < 0.05). We conclude that children receiving peritoneal dialysis with nasal carriage of S. aureus are at a greater risk of developing a S. aureus dialysis-related infection. The treatment of nasal carriage in this population decreased the risk of a S. aureus dialysis-related infection. PMID- 7999850 TI - Computer interaction: demographics, adequacy, and nutrition. AB - Over 700 people attending the Opening Session of the Fourteenth Annual Peritoneal Dialysis Conference participated in the computer interaction exercise as keyboard responders. Responders were 50.5% nurses and 40.4% physicians. Of these, 70.4% were from North America and 19.6% were from Europe. Only 9.5% had been involved in chronic peritoneal dialysis for less than one year. Over half (56%) worked in programs with more than 30 chronic peritoneal dialysis patients. Their own personal choice of dialysis therapy was a form of chronic peritoneal dialysis in 82%. Serum albumin concentration was indicated as the main monitor of nutritional status by 79.1%. Dietary protein intake ranging from 1-1.2 was considered the preferred goal by 84.4% of responders, even though the majority of chronic peritoneal dialysis patients probably do not achieve dietary protein intake in this range. A minimum weekly KT/V urea of 1.7 was chosen as a minimum target by 53.4%. An increase in exchange volume was the most frequently chosen approach to the large, anuric, low-peritoneal transporter. Numerous other questions dealing with adequacy and nutrition were posed to the audience, and the findings are summarized herein. PMID- 7999851 TI - Peritoneal filtration fraction (PFF). AB - The aim of these studies was an evaluation of peritoneal filtration fraction (PFF) in uremic patients dialyzed using 1.5% glucose peritoneal dialysis solution: 1. with pH 6.22 +/- 0.01, without any drugs; 2. adjusted to pH 7.25 +/- 0.02 with 1 M NaOH, without any drugs; 3. as 1. but with the addition of sodium nitroprusside (5 mg/L); 4. as 1. but with the addition of chlorpromazine (2.5 mg/L); 5. as 1. but with the addition of isoprenaline HCL (0.5 mg/L). Investigations with every kind of solution (1.-5.) were carried out in 10 patients. PFF (%) was calculated as [formula: see text] where nUFR (mL/min) = net ultrafiltration rate; Hct (L/L) = hematocrit; EPBF (mL/min) = effective peritoneal capillary blood flow estimated as diffusive mass transfer coefficient of carbon dioxide gas. It was shown that alkalinization of dialysis solution, sodium nitroprusside, or chlorpromazine do not influence PFF, whereas isoprenaline HCL (0.5 mg/L) increases PFF when added to the dialysis solution of pH = 6.22. PMID- 7999852 TI - Comparison of peritonitis rates in children on CAPD with spike connector versus two disconnect systems. AB - The hospital records of all patients on continuous ambulatory peritoneal dialysis (CAPD) who were followed from January 1992 to June 1993 in a third level pediatric hospital were retrospectively reviewed to compare the peritonitis rates of groups of patients according to the dialysis system employed. All patients had Tenckhoff catheters installed by open technique. The groups were A) traditional spike connection system (37 patients), and B) disconnect systems (16 patients) that comprised the O-set system (10 patients) and the basic Y-set system (6 patients). Age was 11.9 +/- 3.7 years (mean +/- SD, range 3 months to 17 years). Follow-up time was 8.5 +/- 4.6 months for the traditional system group (304 cumulated months) and 7.2 +/- 3.6 months for the disconnect systems group (116 cumulated months). Peritonitis rates were 1 episode every 10 months for group A, versus 1 episode every 58 months for group B (p < 0.05). Our results strongly suggest that disconnect systems for peritoneal dialysis can significantly decrease peritonitis rates, although longer follow-up periods are needed. PMID- 7999853 TI - Use of private duty nurses for daily CCPD and family relief in pediatric PD patients. AB - STUDY OBJECTIVE: To evaluate the role of trained home nurses in the care of end stage renal disease (ESRD) pediatric patients on continuous cycling peritoneal dialysis (CCPD) and/or for family relief. DESIGN: The study was designed to investigate trained home nurses in the care of pediatric ESRD patients receiving peritoneal dialysis (PD) who entered the home program between February 1991 and October 1993. SETTING: Tertiary-referral university hospital. PATIENTS AND METHODS: We trained the nursing staff of nursing agencies to perform PD with a special emphasis on pediatric care. A weekly nursing summary including daily vital signs, PD flow sheet, medications, and progress notes was sent to the home program. The trained nurses were also utilized for family relief to prevent burn out. RESULTS: Five children (4 female, 1 male) with ages ranging from 3-14 years were studied. The total number of patient-months was 81 with a range of 4-33 patient-months. During this time, there was only one hospital admission for hyperkalemia and hypertension. Five episodes of peritonitis occurred over 81 patient-months, and all were treated at home. The clinic visit compliance was 100% in patients having nursing help. The administration of erythropoietin at home in these patients was consistent, resulting in higher hematocrit (Hct) levels. The added support to patients and family resulted in a low incidence of complications and infrequent need for hospital admissions. CONCLUSIONS: Our experience suggests that the use of private duty nurses for performing CCPD or for family relief in ESRD children has a favorable outcome and would benefit most pediatric home dialysis programs. PMID- 7999854 TI - Optimization of CCPD prescription in children using peritoneal equilibration test. AB - Continuous cycling peritoneal dialysis (CCPD) is automatically performed by a cycler as a repetition several times per session of the same programmed exchange. We have investigated the efficiency, in terms of ultrafiltration (UF) capacity and solute clearance (phosphate), of an adapted (optimized) CCPD versus a conventional CCPD. Adapted CCPD was performed manually in order to allow a combination of short dwell times (optimal ultrafiltration) and long dwell times (optimal purification). The ratio of ultrafiltration over glucose absorbed (UF/G) was higher with adapted CCPD (5.7 +/- 0.8) compared with conventional CCPD (4.8 +/- 1.3). Phosphate purification was also enhanced with adapted CCPD (0.21 +/- 0.05 versus 0.16 +/- 0.05 mL/min/kg). These results confirm the usefulness of the concept of adapted CCPD with variable dwell times for optimization of peritoneal dialysis performances in children. PMID- 7999855 TI - Higher KT/V urea associated with greater protein catabolic rate and dietary protein intake in children treated with CCPD compared to CAPD. Mid-European Pediatric CPD Study Group (MPCS). AB - Being more suitable to children's lifestyle habits, continuous cycling peritoneal dialysis (CCPD) is becoming the treatment modality of first choice in the pediatric CPD population. In order to establish whether these regimens, prescribed on an empirical basis, provide an equally effective dialysis as does standard continuous ambulatory peritoneal dialysis (CAPD), we performed a cross sectional analysis of dialysate and residual renal small molecule clearances in 85 children aged 3 months to 20 years, who were treated in 16 pediatric dialysis centers. Forty-three children were on CAPD and 42 were on CCPD. The two patient groups did not differ in age, body size, duration of dialysis, underlying disease distribution, or residual renal function. The CAPD patients achieved an average daily drain volume of 159 +/- 40 mL/kg body weight, as compared to 208 +/- 95 mL/kg in the CCPD group (p < 0.005). Average serum creatinine and BUN values were similar in both groups. While the (total) creatinine clearance did not differ, the KT/V urea was significantly higher in the patients treated with CCPD (0.35 +/ 0.12 vs 0.28 +/- 0.13, p < 0.05). The estimated protein catabolic rate (PCR) was significantly higher in the CCPD group (1.39 +/- 0.6 g/kg d) than in the CAPD patients (1.08 +/- 0.48 g/kg d, p < 0.05). Three-day dietary histories, available in 20 patients, showed a similar difference in dietary protein intake between CCPD and CAPD patients. We conclude that CCPD treatment regimens, at the dose currently prescribed in Mid-European pediatric dialysis centers, provide a higher clearance of urea and, possibly, other small molecules.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7999856 TI - A multicenter study on the hospitalization of pediatric patients on chronic peritoneal dialysis. AB - The Italian Registry of Pediatric Chronic Peritoneal Dialysis (CPD) carried out a special study on patient hospitalization during the years 1989-1992. Ninety-two children (mean age 8.4 +/- 4.7 years) entered the study, for a total of 1406 CPD months. The contribution of the different causes of hospitalization for a total of 4683 hospital days was: CPD training 31%; routine controls 14%; CPD-related complications 35%; clinical complications 14%; other causes 6%. The rate of patient hospitalization that resulted was 3.33 days/CPD-month; it was higher in the first year (4.32 days/CPD-month) than in the second year (1.64 days/CPD month) or in the third year (2.25 days/CPD-month). This difference was mainly due to the need for the training at the start of the CPD treatment. The evaluation of the hospitalization rate in different age groups showed a statistically significant difference (p < 0.05) between the group 0-2 years (5.47 days/CPD month) and the group 3-15 years (2.78 days/CPD-month). Complications were the cause of 150 admissions to the hospital (1:9.6 CPD-months). Ninety-eight admissions were due to CPD-related complications: peritonitis (33%), problems with the catheter (19%), abdominal hernias (4%), and others (9%). Among clinical complications (52 admissions), the main cause of hospitalization was hypertension (15%), followed by infections (4%), and malnutrition (3%). PMID- 7999857 TI - Increased need of erythropoietin during peritonitis in children on continuous peritoneal dialysis. AB - Ten continuous ambulatory peritoneal dialysis (CAPD) patients experienced 23 episodes of peritonitis and were treated with intraperitoneal (IP) antibiotics as per sensitivity report. Serum ferritin was measured before and after the treatment. In 6 patients, erythropoietin (EPO) was also measured before and after the treatment. There was a significant drop in the serum EPO levels after therapy compared to the levels before, whereas serum ferritin levels did not change. PMID- 7999858 TI - Stimulation of growth by recombinant human growth hormone in children undergoing peritoneal or hemodialysis treatment. German Study Group for Growth Hormone Treatment in Chronic Renal Failure. AB - Fourteen patients on hemodialysis (HD) and 17 patients on continuous peritoneal dialysis (CPD) were treated with 28-30 IU/m2/week of recombinant human growth hormone (rhGH) for at least 12 months. The HD and CPD patient groups were comparable with regard to age, bone age, height standard deviation scores (SDS), and height velocity at start of treatment. During the first year of rhGH treatment, height velocity increased from 2.9 +/- 1.9 to 5.5 +/- 1.7 cm/year in the HD group and from 3.0 +/- 2.2 to 7.2 +/- 3.2 cm/year in the CPD group. The increase in growth rate was significant in both groups (p < 0.001), and tended to be significantly greater in the CPD than in the HD group (p = 0.09). The marked acceleration of growth under rhGH treatment resulted in an increase in relative height by 0.37 +/- 0.38 SDS in the HD group and by 0.47 +/- 0.69 SDS in the CPD group during the first treatment year. Seven HD and 7 CPD patients completed a second year of rhGH treatment. In these patients, height velocity dropped to 3.6 +/- 2.7 cm/year (HD) and 3.6 +/- 2.3 cm/year (CPD), respectively during the second treatment year. We conclude that rhGH treatment accelerates growth in children both on HD and CPD. The treatment response tends to be greater in CPD compared to HD patients. The efficacy of treatment decreases considerably during the second treatment year. PMID- 7999859 TI - Reproducibility of peritoneal equilibration test (PET) in rats. AB - The aim of the study was to investigate the reproducibility of the peritoneal equilibration test (PET) for evaluating changes in peritoneal function in a rat model of peritoneal dialysis. A PET with 4.25% Dianeal was performed twice within 48 hours under similar conditions after a catheter insertion (n = 10). No significant differences were found between the D/P ratios of PET 1 and PET 2 for urea nitrogen, creatinine, total protein, and D/D0 ratio for glucose. The results for PET 1 and PET 2 showed highly significant correlations. This study indicates, when carried out under similar conditions, that the PET is a highly reproducible test and can be used to evaluate the function of the peritoneum during peritoneal dialysis in rats. PMID- 7999860 TI - Peritoneal equilibration test in Chinese patients. AB - Since the introduction of the peritoneal equilibration test (PET) by Twardowski in 1987, it became a widely accepted test that provided useful prognostic information on continuous ambulatory peritoneal dialysis (CAPD). It had been shown to be a readily reproducible test if the standard procedure was followed. Although there was wide interpersonal difference in the test results, the mean and range (and standard deviation, SD) were remarkably similar as suggested by Davies et al. in 1993 (3). We had performed PET on our CAPD patients for a few years, and all along we used the reference range established by Twardowski to classify our patients into High, High average, Low average, and Low transporters because no reference range had ever been established in Chinese. The aim of this study was to define the normal mean and range of the PET results in Chinese CAPD patients. We analyzed 100 PET results from 100 Chinese CAPD patients. The mean +/ (SD) of the ratio of dialysate/plasma of creatinine and glucose at four-hour dwell times were 0.71 (0.15) and 0.37 (0.12), respectively. There was a significant difference in the dialysate/plasma ratio of creatinine (p < 0.01) while that of glucose was similar when compared with those found by Twardowski. There was no difference in the solute transfer in diabetic and nondiabetic patients. We concluded that the creatinine clearance of the peritoneal membrane in Chinese CAPD patients was higher than the previously reported result in North American patients. PMID- 7999861 TI - Absorption of iron from the peritoneal cavity of rats. AB - The purpose of this study was to determine absorption rate and toxicity of intraperitoneal iron in rats. Twelve (12) male S-D rats were divided into two groups. Group 1 was given 1.5% Dianeal containing 4 mg/L of iron as ferric chloride and group 2 was given standard 1.5% Dianeal. Preblood samples were obtained at the start of the experiment, and 25 mL of the designated dialysis solution was injected into the peritoneal cavity. Six hours after injecting the solution, the dialysate was drained and post-blood samples were obtained. A specimen for histological examination was taken from each rat at the end of the experiment. The iron concentrations of preserum, postserum, dialysis solution with and without added iron, and drained dialysate, were determined. No remarkable changes of serum iron concentration were observed with the six-hour cycle time. Sixty percent of the injected iron was absorbed. No acute toxicity to the peritoneum was observed. PMID- 7999862 TI - The pharmacokinetics of acetazolamide during CAPD. AB - Acetazolamide is a carbonic anhydrase inhibitor commonly used to reduce intraocular pressure (IOP). We report the first pharmacokinetic study of acetazolamide in a patient undergoing continuous ambulatory peritoneal dialysis (CAPD). The patient was a Type I diabetic with end-stage renal disease (ESRD) undergoing CAPD who received acetazolamide for elevated IOP after surgery for a detached retina. Serum acetazolamide concentrations were measured prior to a 250 mg oral dose and 12 additional times during a 24-h dosing interval. All dialysate effluent was collected and assayed for acetazolamide. Serum concentrations at the beginning and end of the dosing interval were 18 and 17 mcg/mL, respectively, with a maximum concentration of 27 mcg/mL at 6.5 h (therapeutic range = 5-10 mcg/mL). The elimination half-life was prolonged, 28.5 h, compared to that seen in subjects with normal renal function (5-10 h). CAPD did not remove a clinically significant amount of drug (17.1 mg, or 6.8% of dose recovered in dialysate). The patient was very lethargic during therapy, a possible manifestation of acetazolamide toxicity. Marked reduction in acetazolamide dosage (in this case, 125 mg/day) would be required to prevent drug accumulation and toxicity. PMID- 7999863 TI - Serum albumin and body surface area are the strongest predictors of the peritoneal transport type. AB - The peritoneal equilibration test (PET) is used as a tool for dialysis prescription. In order to establish which parameters can predict peritoneal transport type, we studied 55 patients on continuous ambulatory peritoneal dialysis (CAPD), who were subjected to a standard PET. Clinical data (sex, age, calculated body surface area [BS], average time on dialysis [TD], and presence of diabetes mellitus), laboratory variables, (serum creatinine [SCr] blood urea nitrogen [BUN], serum albumin [SA], and residual renal function), and adequacy parameters (dialysate creatinine clearance [CrCl], weekly clearance of urea normalized to total body water [KT/V], protein catabolic rate, and dialysis index), were obtained and recorded at the time of the PET. The study group was composed of 29 males and 26 females, mean age of 43.5 +/- 16 years, and average TD of 25.2 +/- 18 months. PET results: 13 patients were low, 16 low average, 19 high average, and 7 high peritoneal transporters. According to the logistic regression analysis, the factors significantly associated with the type of peritoneal transport were: BS, SA, dialysate CrCl, and TD (coefficients 7.2, 1.23, 0.72, and -0.03, respectively). Greater BS and lower SA directly correlate with high peritoneal transport, and are the strongest predictors for the model. PMID- 7999864 TI - How well is hypertension controlled in CAPD patients? AB - To determine how well hypertension is controlled in continuous ambulatory peritoneal dialysis (CAPD) patients, we monitored the blood pressure of 31 hypertensive adult CAPD patients treated with antihypertensive agents. Blood pressure (BP) monitoring, using a noninvasive, ambulatory BP monitor, began in the morning and continued every 30-60 min for 24 h (mean 42 readings per patient). The mean BP of all patients over 24 h was 145.6/91.3 mm Hg. In these, 40.5% of systolic BP readings exceeded 150 mm Hg and 50.2% of diastolic readings exceeded 90 mm Hg, suggesting that hypertension was inadequately controlled for a considerable period of time. Diabetic patients had even worse control of BP. Mean BP, heart rates, and BP loads were not different, between daytime or nighttime. These findings suggest that CAPD patients do not preserve the normal circadian rhythm of BP and that their hypertension is not controlled any better during the night than during the day. We repeated BP monitoring after adjustment of antihypertensive medications in 8 patients who had poorly controlled hypertension. Systolic and diastolic BP loads in subsequent studies improved significantly from the first study. IN CONCLUSION: hypertension is suboptimally controlled in most CAPD patients; diabetic patients fare even worse in the control of hypertension; most patients do not preserve the circadian rhythm of BP and there is no difference in the adequacy of hypertension control during the day or at night; assessment of hypertension with ambulatory BP monitoring helps guide therapy and control of hypertension. PMID- 7999865 TI - Measurement of hydrostatic intraperitoneal pressure. Altir Nursing Team. AB - We present the nurse's procedure for routine measurement of intraperitoneal hydrostatic pressure (IPP). It is very easy, simple, and safe. We measure the height of dialysis fluid in the peritoneal dialysis (PD) line before drainage. The level of the column of dialysate is measured with a scale, expressed in centimeters of water. The patient rests in a strictly horizontal position and the zero level is set at the medial axillary line. Two measurements are taken: one when breathing in and the other when breathing out. The IPP must be measured at atmospheric pressure without any counterpressure. Therefore, two techniques exist, depending on the geometry of the PD system. With disconnect systems, there is no counterpressure in the line and the empty drainage bag. With nondisconnect systems, there is always a counterpressure in the line because an air inlet is necessary. The measurement of IPP is an important element in the medical prescription of intraperitoneal volumes for adequate dialysis and to prevent mechanical complications. Normal values are established in patients undergoing CAPD treatment: IPP insp. = 14 +/- 2 cmH2O and IPP exp. = 12 +/- 2 cmH2O. PMID- 7999866 TI - APD: clinical measurement of the maximal acceptable intraperitoneal volume. AB - In automated peritoneal dialysis (APD) patients treated with 3-L dwell, intraperitoneal volumes can easily be increased up to 4 or 4.5 L using hypertonic solutions without objective control of their good tolerance. In 20 adult patients treated with continuous ambulatory peritoneal dialysis (CAPD) in good conditions, hydrostatic intraperitoneal pressure (IPP) and pulmonary vital capacity (VC) were measured in strict supine position, after infusing isotonic dialysate in 0.5-L increments from 2 up to 5 L as tolerated, according to intraperitoneal volumes (IPV). None of the patients had cardiac or pulmonary dysfunction. IPP was measured following a routine method previously described. In all cases, experience was stopped when IPP increased over 20 cm H2O and/or VC decreased over 25%. IPV is linearly and positively correlated with IPP (p < 0.0001), and negatively with VC (p = 0.0012), but the reliability of VC is less than that of IPP, particularly in old patients. Clinical symptomatology of bad IPV tolerance never occurred alone and was always associated with an increase in IPP over 20 cmH2O and/or a decrease in VC over 25%. The maximal acceptable IPV is better defined by an IPP less than 18 cmH2O, according with a decrease in VC of less than 20%. Routine measurement of IPP can be used to determine maximal IPV and for optimal PD prescription. PMID- 7999867 TI - Is overhydration in CAPD patients a contraindication to renal transplantation? AB - Over a 14 year period, 56 of 415 CAPD patients (34 male, 22 female), aged 42.7 +/ 11 years, underwent renal transplantation (TR). A cadaver kidney was used in 53 patients (kidney-pancreas in 2), and a human leucocyte antibody (HLA) identical related donor organ was used in 3. Underlying renal diseases were chronic glomerulonephritis in 30 patients, diabetic nephropathy in 10, interstitial nephropathy in 5, vascular in 4, polycystic kidney in 3, and undetermined in 4. Mean duration of CAPD prior to TR was 13 months (2-56 months). A three-week peritonitis episode-free interval was requested prior to TR. At year 1, actuarial patient and graft survival (96% and 86%, respectively), plasma creatinine, and number of rejection episodes were not different from those recorded in patients treated with hemodialysis (HD) prior to TR. At TR, pulmonary artery pressure (PAP) was elevated (average 21.1 +/- 7.4 mm Hg), > or = 25 mm Hg and > or = 30 mm Hg in 36% and 14.6% of CAPD patients, respectively. Post-TR, HD was performed in 4 patients; no peritoneal infection occurred. Postoperative sonography disclosed ascitis in 12.7% of CAPD patients. The PD catheter was removed two months post TR. Hemodynamic findings at TR suggest a frequently underestimated overhydration in CAPD patients, which should be detected and treated in order to reduce acute cardiovascular complications at TR. PMID- 7999868 TI - CAPD for treatment of ESRD patients with ascites secondary to liver cirrhosis. AB - The treatment of cirrhotic patients with ascites and end-stage renal disease (ESRD) is complex. Continuous ambulatory peritoneal dialysis (CAPD), as a continuous therapy, represents an alternative to hemodialysis-associated hemodynamic intolerance. We report our experience with 5 cirrhotic patients with ascites who were treated by CAPD. Three had been transferred from hemodialysis (HD) for intolerance. The hemodynamic tolerance was excellent in all patients, and solute and water peritoneal transport were increased over the normal range in all cases. Morbidity was principally related to liver disease. Peritoneal protein losses, initially high, decreased over time. Serum albumin was within the low normal range. The incidence of peritonitis was higher than usual in these patients; episodes caused by gram-negative bacteria, streptococci and listeria, were predominant. The cause of death was not CAPD-related. In our experience, CAPD should be the treatment of choice for cirrhotic patients with ascites who require dialysis. PMID- 7999869 TI - Vascular disease outcome and thrombocytosis in diabetic and nondiabetic end-stage renal disease patients on peritoneal dialysis. AB - STUDY OBJECTIVE: to evaluate vascular disease and its outcome in association with thrombocytosis in chronic peritoneal dialysis (PD) patients. DESIGN: the study was designed to investigate possible correlations between severity of vascular disease and thrombocytosis in PD patients. SETTING: tertiary-referral university hospital. PATIENTS AND METHODS: serial blood platelet levels were measured in 53 stable PD patients (32 male, 21 female; mean age 55 years; mean duration of PD 19 months) between January 1991 and July 1992. Twenty-four patients were diabetic and 29 were nondiabetic. Mean duration of PD was 23 and 36 months in diabetic and nondiabetic patients, respectively. Severity of coronary arterial disease (CAD), carotid arterial disease (CNS), and peripheral arterial disease (PAD) was assessed using the Craven et al. (1991) ESRD Severity Index, a measure of organ dysfunction. Functional status was assessed using the Karnofsky Performance Status Index (KPSI). RESULTS: eighteen out of 53 PD patients (34%) had platelet counts exceeding 300,000/mm3 for six months or longer. Thirteen of 24 diabetic PD patients (54%) had thrombocytosis. Blood platelets were significantly (p < 0.01) higher in diabetic (324,000 +/- 27,000/mm3) than in nondiabetic PD (236,000 +/- 11,000/mm3) patients. In the PD group as a whole, a positive correlation was observed between blood platelet and serum cholesterol (r = 0.5, p < 0.001), blood platelet and PAD (r = 0.5, p < 0.001), and blood platelet and CAD (r = 0.35, p < 0.05). No correlation was found with age or duration of PD. In diabetic PD patients, blood platelet counts correlated significantly with PAD (r = +0.5, p < 0.01) and CAD (r = +0.4, p < 0.05) indexes. No correlation was observed between blood platelet and CNS or KPS indexes. In nondiabetics, no correlation was observed between blood platelet and CAD, PAD, CNS, or KPS indexes. CAD, PAD, and KPS indexes were significantly higher in diabetics compared to nondiabetics. CONCLUSIONS: thrombocytosis, particularly in diabetic PD patients, appears to be associated with the severity of PAD and CAD. PMID- 7999870 TI - Long-term successful nocturnal intermittent peritoneal dialysis: a ten-year case study. AB - We report a case of polycystic kidney disease, successfully dialyzed using nocturnal intermittent peritoneal dialysis (NIPD) for ten years. Other forms of renal replacement therapy, which included hemodialysis, continuous ambulatory peritoneal dialysis (CAPD), intermittent peritoneal dialysis (IPD), and renal transplantation, were unsuitable for the patient. A peritoneal equilibration test revealed a 4-h D/P creatinine (Cr) ratio of 0.54. In January 1984, the patient began NIPD for 12 h, using a dialysis solution dose of 14 L/day, and 2 L/exchange. In January 1986, because of clinical under-dialysis, the dialysis solution dose was increased to 20 L/day, with an exchange volume of 1.57 L. The prescribed outflow time was 20 min. Dialysis was still inadequate with a weekly corrected Cr clearance (CoCrCl/w) of 33.6 L. In August 1986, the outflow time was reduced to 14 min and the total dialysis time to 11 h. Despite the latter, the efficiency of dialysis was greater because of longer full contact between dialysate and peritoneum. The last change resulted in marked clinical improvement and CoCrCl/w increased to 39.9 L. Over the years, the patient's peritoneal transport changed to high average (4-h D/P Cr = 0.74) and NIPD provided even better clearances (CoCrCl/w = 59.96 L in 1994). The report emphasizes that NIPD, if properly tailored, can provide clinically adequate long-term dialysis. PMID- 7999871 TI - Abdominal wall hernias in ESRD patients receiving peritoneal dialysis. AB - The study was designed to investigate the incidence of abdominal wall hernias (AWH) and related outcome in all end-stage renal disease (ESRD) patients who started peritoneal dialysis (PD) from January 1989 to December 1993. Between January 1989 and December 1993, a total of 158 ESRD patients (93 male, 65 female) entered our home program and were treated with peritoneal dialysis (PD) over 2789 patient-months. All PD catheters were placed in the lateral by two dedicated surgeons. AWH detected at the time of PD catheter placement was repaired simultaneously. The hernia repair was done using a polypropylene mesh. Inguinal hernias were noted by patients as a mass or discomfort. Umbilical and incisional hernias were observed during clinic visits. Twenty-one (13.3%) abdominal wall hernias were observed in 20 patients (12.7%). Eight (38.1%) inguinal hernias occurred in 8 male patients. Six inguinal hernias were repaired. PD was resumed after a mean of 12 days of hernia repair. Two patients resumed PD in 8 and 14 days without dialysis. One patient transferred to hemodialysis (HD) due to catheter malfunction. No complications occurred related to inguinal hernias. Ten (47.6%) umbilical hernias were observed in 10 patients (7 male, 3 female). The strangulation of umbilical hernias occurred in 2 patients, which required emergency small bowel resection and hernia repair. Both cases were complicated by candida peritonitis and enterobacter peritonitis, requiring PD catheter removal, and patients were then transferred to HD. Three (14.3%) incisional hernias were observed in 3 male patients. Two incisional hernias were repaired. No relation between AWH and PD modalities (CAPD/CCPD/IPD) was observed.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7999872 TI - Selected outcome criteria and adequacy of dialysis in diabetic and elderly patients on CAPD therapy. AB - There has been a gradual increase in the number of diabetic and elderly patients maintained on continuous ambulatory peritoneal dialysis (CAPD) replacement therapy. Eighty randomly selected patients were studied over two years. Weekly normalized urea clearance (KT/Vurea), weekly creatinine clearance/1.73 m2 body surface area (BSA) (Ccr), and protein catabolic rate (PCR) were measured. Selected clinical outcome criteria were assessed. Weekly KT/Vurea was correlated with weekly Ccr (r = 0.538, p < 0.001), and weekly KT/Vurea was correlated with PCR (r = 0.393, p < 0.001). Patients were then stratified according to presence or absence of diabetes mellitus and age > 60 or < or = 60 years. Diabetic and nondiabetic patients had similar weekly KT/Vurea, weekly Ccr, PCR, serum albumin levels, weekly erythropoietin (EPO) requirements, peritonitis rates, and CAPD related hospitalization rates. The total hospitalization rates, however, were higher in diabetic patients. Elderly and younger patients had similar weekly KT/Vurea, weekly Ccr, PCR, serum albumin levels, and weekly EPO requirements. Elderly patients, however, had higher peritonitis rates and higher total and CAPD related hospitalization rates. PMID- 7999873 TI - Serum albumin: associations and significance in peritoneal dialysis. AB - Hypoalbuminemia in hemodialysis patients is a strong predictor of mortality; however, the significance of hypoalbuminemia in peritoneal dialysis patients is less well-defined. We have analyzed the factors associated with hypoalbuminemia in a cross-sectional study of 36 peritoneal dialysis patients, and investigated the impact of hypoalbuminemia on the one-year clinical outcome in 53 peritoneal dialysis patients. We found hypoalbuminemia to be associated with low values for the kinetic parameters KT/V, creatinine clearance, and normalized protein catabolic rate (nPCR) by univariant analysis. In a multiple regression model, nPCR was the only significant predictor of serum albumin. Clinical outcome measures evaluated were days-hospitalized, peritonitis rate, and death. Days hospitalized was inversely correlated with serum albumin, and deaths occurred only in patients with serum albumin less than 4.0 mg/dL. There were no associations with peritonitis episodes. In conclusion, our study provides evidence that hypoalbuminemia in peritoneal dialysis patients is associated with a low protein intake measured by the nPCR and, possibly, with a low delivered dose of dialysis. Our study also suggests that the serum albumin level correlates to clinical outcome measured by days-hospitalized. PMID- 7999874 TI - Lean body mass by Dual Energy X-ray Absorptiometry (DEXA) and by urine and dialysate creatinine recovery in CAPD and pre-dialysis patients compared to normal subjects. AB - The urinary creatinine excretion rate is a function of the muscle mass which, in normal subjects, is shown to be correlated with lean body mass. Dual Energy X-ray Absorptiometry (DEXA) has been shown to correlate well with other methods for the measurement of body composition. The purpose of the present study was to compare estimates of lean body mass (LBM) by DEXA scan with urine and dialysate creatinine recovery in uremic patients and in normal subjects. We included 63 normal subjects with a creatinine clearance of 60-120 mL/min, 30 uremic predialysis patients with creatinine clearance below 30 mL/min, and 20 continuous ambulatory peritoneal dialysis (CAPD) patients. LBM was measured by DEXA scan on the same day as urine collection and was estimated from creatinine recovery with and without correction for extrarenal creatinine clearance. Results from the normal subjects showed no difference in estimates of LBM by the different methods but, in predialysis and CAPD patients, a significant difference between methods of estimating LBM was found, even when correction for extrarenal clearance in uremic patients was performed. In normal subjects: DEXA 43.6 kg versus creatinine excretion 43.2 kg (NS). In predialysis patients: DEXA 47.8 kg versus 37.6 kg (p < 0.001) corrected 44.8 kg (p < 0.05). In CAPD patients: DEXA 47.2 kg versus 32 kg (p < 0.001) corrected 42.6 kg (p < 0.05). In conclusion, the urine and dialysate creatinine excretion is an inaccurate estimate of LBM, but reflects the muscle mass and, in that respect, is an important tool in the nutritional evaluation of uremic patients.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7999875 TI - Frequency dependence of the action-perception cycle for postural control in a moving visual environment: relative phase dynamics. AB - When standing human subjects are exposed to a moving visual environment, the induced postural sway displays varying degrees of coherence with the visual information. In our experiment we varied the frequency of an oscillatory visual display and analysed the temporal relationship between visual motion and sway. We found that subjects maintain sizeable sway amplitudes even as temporal coherence with the display is lost. Postural sway tended to phase lead (for frequencies below 0.2 Hz) or phase lag (above 0.3 Hz). However, we also observed at a fixed frequency, highly variable phase relationships in which a preferred range of phase lags is prevalent, but phase jumps occur that return the system into the preferred range after phase has begun drifting out of the preferred regime. By comparing the results quantitatively with a dynamical model (the sine-circle map), we show that this effect can be understood as a form of relative coordination and arises through an instability of the dynamics of the action perception cycle. Because such instabilities cannot arise in passively driven systems, we conclude that postural sway in this situation is actively generated as rhythmic movement which is coupled dynamically to the visual motion. PMID- 7999876 TI - Numerical study of coding of the movement direction by a population in the motor cortex. AB - The fundamental statistical aspects of population coding of the movement direction in the motor cortex are studied numerically. The activity of neurons in a population is simulated using pseudorandom numbers so that the directional selectivity of the neurons is similar to that observed experimentally. Accuracy of the coding, which is evaluated by the root-mean-square (rms) error, is analyzed for various population sizes, degrees of variability of neuronal activity, and degrees of nonuniformity of distribution of the preferred directions. The dependence of the rms error on the population size shows a good fit to the inverse square-root law, from which it is estimated that a single population must contain around 10,000 neurons in order to attain the accuracy that allows 1 deg rms error, for example. The coding is studied further for populations with different types of tuning function. The results support the hypothesis proposed by Georgopoulos et al. (1988) except that the tuning function 'must be tuned in the sense that the average value of the function for movements with components in the preferred direction is larger than for movements away from the preferred direction'. PMID- 7999877 TI - Neural modeling of the dorsal cochlear nucleus: cross-correlation analysis of short-duration tone-burst responses. AB - A conceptual model of a portion of dorsal cochlear nucleus (DCN) neural circuitry has emerged over the past two decades. This model suggests that the response properties of the DCN's major projection neurons, called type IV units, are due, in part, to the behavior of local circuit inhibitory interneurons called type II units (Young and Brownell 1976). Cross-correlation studies of simultaneously recorded pairs of DCN units in decerebrate cat derived from 50-s best frequency (BF) stimuli are consistent with and have extended this conceptual model (Voigt and Young 1980, 1985, 1988, 1990). Interestingly, Gochin et al. (1989) found no signs of inhibition in the anesthetized rat DCN in cross-correlograms derived from 55-ms short-duration BF tone bursts. This seemingly contradictory result has motivated this study. Computer simulations were run using our network model of the intrinsic DCN neural circuitry. This model has previously been shown to reproduce the major features of both type II and type IV rate-level curves and the inhibitory trough (IT) observed in cross-correlograms derived from long duration stimuli (Voigt and Davis 1994). The goal was to study the stimulus duration-dependent strength of ITs in the cross-correlograms derived from short duration BF tone-burst stimuli. The results suggest that ITs may not be detectable when the stimulus duration is 50 ms but may be detectable when the stimulus duration is 200 ms or greater. Furthermore, when the ITs are detected in cross-correlograms derived from 200-ms data sets, the strength of the IT, as measured by effectiveness, is comparable to the strength of ITs measured when the stimulus duration is 50 s. PMID- 7999878 TI - Processing of hierarchic stimulus structures has advantages in humans and animals. AB - Carmesin and Schwegler (1994) have determined theoretically that a linear hierarchical stimulus structure can be encoded by a parallel network of minimal complexity. The experiments reported here compare the efficiency with which humans and pigeons process sets of stimulus pairs embodying different inequality structures. Groups of subjects of each species were taught to discriminate all 10 pairwise combinations of 5 stimuli with an operant conditioning method. For one group, the reward/punishment allocations within the pairs agreed with a linear hierarchy. For a second and third group, the reinforcement allocations of one or three, respectively, of the stimulus pairs deviated from such ordering. The time it took the subjects to learn the tasks as well as the final choice latencies and/or error rates increased with the number of deviating inequalities. The results agree with the assumption that both humans and pigeons encode stimulus inequality structures with parallel processing neural networks rather than with a sequentially processing algorithm. PMID- 7999879 TI - Analytical solutions to the multicylinder somatic shunt cable model for passive neurones with differing dendritic electrical parameters. AB - The multicylinder somatic shunt cable model for passive neurones with differing time constants in each cylinder is considered in this paper. The solution to the model with general inputs is developed, and the parameteric dependence of the voltage response is investigated. The method of analysis is straightforward and follows that laid out in Evans et al. (1992, 1994): (i) The dimensional problem is stated with general boundary and initial conditions. (ii) The model is fully non-dimensionalised, and a dimensionless parameter family which uniquely governs the behaviour of the dimensionless voltage response is obtained. (iii) The fundamental unit impulse problem is solved, and the solutions to problems involving general inputs are written in terms of the unit impulse solution. (iv) The large and small time behaviour of the unit impulse solution is examined. (v) The parametric dependence of the unit impulse upon the dimensionless parameter family is explored for two limits of practical interest. A simple expression for the principle relationship between the dimensionless parameter family is derived and provides insight into the interaction between soma and cylinders. A well posed method for the solution of the dimensional inverse problem is presented. PMID- 7999880 TI - Breed differences in the phenotype and gene frequencies in canine D blood group system. AB - The D system of canine blood groups was studied in 3,191 dogs of many different breeds. The frequencies of the D system phenotypes and genes were measured. These frequencies varied considerably between the breeds native to Japan. The frequency of the D1 phenotype was higher in breeds native to Japan than in those of non Japanese origin. Conversely, non-Japanese breeds generally had the D2 phenotype. The dogs described as mongrel in Japan had D system frequencies intermediate between native Japanese and non-Japanese breeds. One of the most interesting findings was that in the Afghan bound the frequency of the D1 gene (0.3333) was the same as in the Shiba, though only the Shiba was native to the Japanese isles. Another Japanese breed was the Tosa, and its D1 gene frequency was 0.063, a value even lower than that for the non-Japanese Maltese (0.097). PMID- 7999881 TI - Survey of natural scrapie in Japan: analysis of RFLP types of the PrP gene and detection of PrPSc mainly in Suffolk sheep. AB - We examined the brains, spleens and/or lymph nodes of 197 mainly suffolk sheep collected from Hokkaido, and the Tohoku, Kanto and Chubu districts to detect PrPSc and thus to estimate scrapie contamination in Japan. Sixteen sheep in Hokkaido and 2 sheep in other districts that were introduced from Hokkaido were positive for PrPSc. By comparison of the frequencies of the restriction fragment length polymorphism (RFLP) types of these 18 scrapie sheep with 128 healthy sheep, we confirmed the association of specific RFLP types of the PrP gene with natural scrapie. The frequency of RFLP type I in scrapie sheep was significantly higher than that in healthy sheep and those of other types in scrapie sheep. In contrast, the frequencies of type II and VI in healthy sheep were higher than those in scrapie sheep. Therefore, type I sheep seemed to be susceptible but type II and VI sheep seemed to be resistant to natural scrapie in Suffolk sheep in Japan. Furthermore, we investigated the distribution of the RFLP types of the PrP gene in 161 sheep in Japan to learn about the genetic background of the susceptibility to scrapie. There were variations in the distribution of the RFLP types in each district. PMID- 7999883 TI - Pathologic observations of pigs intranasally inoculated with serovar 1, 4 and 5 of Haemophilus parasuis using immunoperoxidase method. AB - Nineteen, 7- to 13-week-old pigs were inoculated intranasally with different strains of Haemophilus parasuis (serovar 1, 4 and 5), and the pathological lesions induced by each strain were compared. Eleven of thirteen pigs inoculated with either strain Nagasaki (serovar 5) or No. 4 (serovar 1) died between days 1 to 6 after inoculation, and had septicemic lesions, meningitis, or polyserositis. One of six pigs inoculated with strain SW124 (serovar 4) died with polyserositis, another one recovered after illness, and the remaining four pigs remained in good health. Five of the septicemic pigs had thrombi at many organs. Endotoxin was detected in the plasma of 10 pigs in the acute stage of infection. Using the immunoperoxidase technique, H. parasuis antigen was detected in lesions of infected pigs. In the serosal lesions the bacterial antigen was found mainly in the cytoplasm of infiltrating neutrophils and macrophages and appeared as degenerated bacteria and/or lytic bacterial material in dilated phagosomes. Many of the bacteria in the blood vessels of pigs with septicemic lesions were also degenerated. Although H. parasuis was reisolated from nasal secretions of infected pigs, the bacterial antigen could not be detected in the nasal cavities of these pigs. No lesions were observed in the parenchyma of the lung. However, H. parasuis antigen was detected in the tonsil of infected pigs. PMID- 7999882 TI - Protection of mice against Aujeszky's disease virus infection by intranasal vaccination with inactivated virus. AB - Intranasal vaccination of mice with inactivated Aujeszky's disease virus (ADV) induced IgA and IgG antibody responses to the virus in the secretion of the respiratory tract, resulting in complete protection of the animals against intranasal challenge with virulent ADV. The immune response was enhanced by the use of the cholera toxin B subunit (CTB) as an adjuvant. On the other hand, subcutaneous vaccination of mice with inactivated ADV, even together with CTB, scarcely stimulated secretory antibody responses, resulting in only partial protection. The present results suggest that development of a vaccination procedure to stimulate the mucosal immune response should improve the protective effects of the inactivated herpesvirus vaccines, and thereby make it possible to control the infections by prohibiting virus replication at the site where primary infection takes place, as well as inhibiting subsequent latency and reactivation of the virus. PMID- 7999884 TI - A therapeutic effect of ulinastatin on endotoxin-induced shock in dogs- comparison with methylprednisolone. AB - The therapeutic effect of ulinastatin (25,000 U/kg, i.v.) on endotoxin-induced shock was compared with that of methylprednisolone (30 mg/kg, i.v.) in 17 anesthetized dogs. Both of these drugs had almost the same tendency to improve the hemodynamics, arachidonate cascade metabolites and pulmonary surface activity. There was little difference between the effectiveness of ulinastatin and that of methylprednisolone. It was newly confirmed that the release of 6-keto PGF1 alpha, thromboxane B2 and leukotriene B4, arachidonate cascade metabolites and chemical mediators associated with endotoxin-induced shock, were significantly (p < 0.01 and p < 0.05) decreased by ulinastatin in the same way as methylprednisolone. These results suggest that ulinastatin is as useful as methylprednisolone for the treatment of endotoxin-induced shock. PMID- 7999885 TI - Myocardiopathy and expression of atrial natriuretic peptide in rats with monocrotaline-induced pulmonary hypertension. AB - Myocardiopathy in rats with monocrotaline (MCT)-induced pulmonary hypertension was investigated morphologically and immunohistochemically. A single subcutaneous injection of MCT (60 mg/kg body weight) to SD rats produced progressive cardiac lesions. Histologically, the lesions were characterized by myocardial hypertrophy and myocardial degeneration followed by mononuclear cell infiltration and fibroblast proliferation in the right atrium and ventricle. Such histological changes began to be seen 3 weeks after injection and thereafter progressively developed in rats killed 4 and 5 weeks after injection. These findings indicate progressive hypertrophic myocardiopathy, due probably to pulmonary hypertension induced by MCT. Immunohistochemically, atrial natriuretic peptide (ANP)-positive myocardial cells were frequently observed in the left and right ventricle in MCT treated rats killed 4 and 5 weeks after injection. The intensive immunopositive reaction was observed mainly in hypertrophic myocardial cells in the subendocardium of the right ventricle and also present in hypertrophic myocardial cells around injured areas consisting of degenerated myocardial cells, mononuclear cell infiltration and fibrosis. These findings suggest a close relationship between the ANP expression and cardiac hypertrophy in MCT-treated rats. PMID- 7999886 TI - Serum biochemical changes and chemiluminescent responses of whole blood in Holstein cattle with leukocyte adhesion deficiency. AB - Serum biochemical profile and whole blood chemiluminescent (CL) responses in 8 Holstein cattle affected with leukocyte adhesion deficiency (LAD) were evaluated. Concentrations of sodium, chloride and calcium in serum from cattle affected with LAD were significantly (p < 0.05) decreased as compared with controls. The characteristic changes in serum proteins were hypoalbuminemia and hyperglobulinemia, and the concentrations of albumin and gammaglobulin in serum from normal cattle and cattle affected with LAD were significantly (p < 0.01) different. Significantly (p < 0.01) diminished CL indices and prolonged peak time of CL responses in whole blood were detected in cattle affected with LAD. These findings indicate that the CL response associated with iC3b receptor mediated phagocytic activity is impaired in cattle affected with LAD. The whole blood CL assay appeared to be practical and useful for routine evaluation of blood samples from cattle affected with LAD. PMID- 7999887 TI - Isolation and characterization of rainbow trout (Oncorhynchus mykiss) serum amyloid P component (SAP) AB - We purified a Ca(2+)-dependent agarose-binding protein from rainbow trout (Oncorhynchus mykiss) sera. SDS-PAGE analysis showed the possibility that the purified protein was a polymer with a molecular weight of over 100,000 composed of covalently-bounded 32-kDa subunits. N-terminal twenty amino acid sequence of the 32-kDa protein showed partial homology with other known serum amyloid P components (SAPs) including plaice (Pleuronectes platessa) (indicated 40% homology), human (55%), hamster (45%), rat and mouse (40%) SAPs. In electron micrographs the 32-kDa protein was observed as pentameric disc-like structure. On the basis of the results, the 32-kDa agarose-binding protein of rainbow trout was concluded to belong to pentraxin family and to be a SAP homologue. PMID- 7999888 TI - Effects of furazolidone on duration of righting reflex loss induced with hexobarbital and zoxazolamine in the rat. AB - Effects of furazolidone (FZ) on the sleeping time induced with hexobarbital (HEX) and paralysis time induced by zoxazolamine (ZOX) were investigated by measuring the length of time required to recover from righting reflex loss in rats after oral administration of FZ at doses of 50, 100, 200 and 400 mg/kg/day for 4 successive days. Administration of 50 mg/kg to rats of both sexes induced no effect on the HEX sleeping time, but of 100 mg/kg FZ or more induced prolongation of sleeping time dose-dependently. In female rats, HEX sleeping time of the control group was twice that of the male rats, but HEX sleeping time after receiving FZ above 200 mg/kg was approximately the same as in the male rats. ZOX paralysis time exhibited no sex differences in the control rats, and it was significantly prolonged by FZ at a dose of 100 mg/kg or more. No significant differences in blood levels of HEX and ZOX at the time of recovery were found between the control and FZ treated rats, suggesting that FZ produced prolongation of the drug effects was due to the maintenance of the blood levels rather than the change in the sensitivities of rats at the receptor sites. Body weight gains were inhibited in the rats treated with FZ at doses over 100 mg/kg. Cytochrome P 450 content in hepatic microsomes in the rats which received 100 mg/kg FZ were slightly increased. It is suggested that successive oral administration of FZ to rats at high doses impaired drug clearance and this resulted in the prolongation of HEX sleeping and ZOX paralysis times. PMID- 7999889 TI - Experimental infection of raccoon dogs with Sarcocystis cruzi and S. miescheriana. AB - Raccoon dogs were successfully infected with Sarcocystis cruzi and S. miescheriana by oral inoculation of infected cardiac muscle of cattle and pigs slaughtered in Saitama and Okinawa prefectures, respectively. Oocysts and sporocysts passed by raccoon dogs were similar in measurements and morphological features as reported of S. cruzi and S. miescheriana respectively. The prepatent and patent periods of both S. cruzi and S. miescheriana were 9 and 66-72 days respectively in raccoon dogs. PMID- 7999890 TI - The bronchial tree and blood vessels of the cow (Holstein) lung. AB - In the lung of the cow (Holstein), the right and left bronchi have the dorsal, lateral, ventral and medial bronchiole systems, respectively. Furthermore, the right lung has a tracheal bronchiole (bronchus). From the standpoint of bronchial ramifications, a bilobed cranial lobe and the middle, caudal and accessory lobes can be discriminated in the right lung, whereas a bilobed middle lobe and a caudal lobe can be discriminated in the left lung. The left cranial lobe is lacking. The right pulmonary artery runs obliquely across the ventral side of the trachea caudally to the origin of the cranial lobe bronchiole. It then runs across the dorsal side of the right middle lobe bronchiole, and thereafter along the dorsolateral side of the right bronchus. During its course, it gives off arterial branches running mainly along the dorsal or lateral side of each bronchiole. The left pulmonary artery runs the same course as that in the right lung. The pulmonary veins run mainly along the ventral or medial side of the bronchiole. PMID- 7999892 TI - Bronchial tree, lobular division and blood vessels of the pig lung. AB - The pig lung has the dorsal, ventral, medial and lateral bronchiole systems on either side. In addition, a tracheal bronchiole (bronchus) arises from the right side of the trachea. According to the bronchial ramification, the right lung consists of the cranial, middle, caudal and accessory lobes, while the left lung consists of the bilobed middle and caudal lobes. The right and left pulmonary arteries run along the dorsolateral side of the right and left bronchi, respectively. During their course, these pulmonary arteries give off arterial branches running mainly along the dorsal or lateral side of each bronchiole. The pulmonary veins run mainly along the medial or ventral side of each bronchiole. PMID- 7999891 TI - Evaluation of a monoclonal antibody-based colony blot test for rapid identification of virulent Rhodococcus equi. AB - We recently generated a monoclonal antibody immunoglobulin G1 (MAb 10G5), which can recognize 15- to 17-kDa antigens, virulence-associated antigens of Rhodococcus equi, and developed a colony blot enzyme-linked immunosorbent assay with MAb 10G5 for the rapid identification of virulent R. equi. In this epidemiologic study, we evaluated the results of the colony blot test in the identification of virulent isolates of R. equi from feces of horses and soil and compared them with those from a conventional procedure (plasmid profiles of isolates by agarose gel electrophoresis). Environmental isolates (778 isolates from feces of foals, 170 isolates from feces of dams, and 1,267 isolates from soil on horse-breeding farms in Hokkaido) were tested by the colony immunoblot test, and 238 of the 778 isolates, 6 of the 170 isolates, and 85 of the 1,267 isolates showed positive signals. Positive isolates were then analyzed for the presence of virulence plasmid DNA, and 235 (98.7%) of the 238 isolates from foals, 6 (100%) of the 6 isolates from dams, and 75 (88.2%) of the 85 isolates from soil showed the presence of virulence plasmids. On the other hand, 50 isolates from each source, which were randomly selected from the isolates that showed negative signals by colony immunoblot, did not contain virulence plasmids. These results demonstrated that the colony blot test that uses a monoclonal antibody specific for virulence-associated antigens is a rapid and reliable test for the identification of virulent R. equi. PMID- 7999893 TI - Immune response and in vivo distribution of the virus in chickens inoculated with the cell-associated vaccine of attenuated infectious laryngotracheitis (ILT) virus. AB - Chickens inoculated with the cell-associated (CA) vaccine acquired higher protective immunity to ILT. In chickens vaccinated with CA or cell-free (CF) vaccine, respectively, virus-neutralizing and IgG- and IgM-ELISA antibodies were detected in the serum, but no antibody was detected in the tracheal washes of the vaccinated chickens. More apparent antibody response was seen in chickens vaccinated with the CA vaccine than with the CF vaccine. The antibody titers did not correlate closely with the protection against challenge with ILT virus. After subcutaneous injection of either CA or CF vaccine, ILT virus was isolated from the liver, spleen, thymus, lungs and other organs of the chickens from 1 to 6 days after injection, and there was no correlation of the isolation rate for the CA-vaccinated and the CF-vaccinated chickens. PMID- 7999894 TI - A survey of Campylobacter jejuni in broilers from assignment to slaughter using DNA-DNA hybridization. AB - A survey of Campylobacter jejuni in the cecal contents of broilers raised on a farm was carried out by the DNA-DNA hybridization method from the day of assignment to slaughter at about 1-week intervals. C. jejuni was detected in chickens as early as 1 week of age, and was widely detected at each week of age throughout the growing period. In addition, of 20 chickens tested just after assignment, 7 (35%) were C. jejuni positive. It is suggested that newly introduced chickens may have already been contaminated with C. jejuni. The hybridization method was able to detect C. jejuni in the chickens from the day of assignment to 3 weeks of age, but C. jejuni was never detected in the same chickens by the enriched culture method. Therefore, it is suggested that the hybridization method is more sensitive than the enriched culture method. PMID- 7999896 TI - Rumen ciliate composition and diversity of Japanese beef black cattle in comparison with those of Holstein-Friesian cattle. AB - The composition of ciliate protozoa in the rumen of 30 Japanese beef black cattle (Bos taurus taurus) fed in Yoron Island, Kagoshima, was compared with that of 125 Holstein-Friesian cattle (Bos taurus taurus) fed in Hokkaido. Thirteen genera including 44 species with 32 formae detected from Japanese beef black cattle and 15 genera including 48 species with 25 formae from Holstein-Friesian cattle were identified. Thirty-six species with 19 formae were common to both hosts. A new species was recognized from Japanese beef black cattle and named Entodinium yunnense n. sp. This new species was classified into such four formae as yunnense n.f., spinonucleatum n.f., acutonucleatum n.f. and spinolobum n.f. A new forma of Entodinium bifidum having only one caudal spine was also recognized from Japanese beef black cattle and named monospinosum n.f. The average ciliate density in Japanese beef black cattle, 18.7 x 10(4)/ml, was lower than 40.3 x 10(4)/ml in Holstein-Friesian cattle. The average number of ciliate species per head in Japanese beef black cattle, 14.4 was also lower than 17.8 in Holstein-Friesian cattle. The average value of diversity index was 1.789 in Japanese beef black cattle and 1.718 in Holstein-Friesian cattle. Both incidence and composition ratio of Entodinium rectangulatum and E. ovinum were significantly higher in Japanese beef black cattle than in Holstein-Friesian cattle. On the other hand, Charonina ventriculi, E. caudatum, E. rostratum, E. parvum, E. bursa, Metadinium affine and Ostracodinium mammosum showed a reverse relation. PMID- 7999895 TI - Simultaneous determination of tetrahydrofolate, 10-formyltetrahydrofolate and 5 methyltetrahydrofolate in rat bile by high-performance liquid chromatography with electrochemical detection. AB - This report describes an analytical method for the measurement of tetrahydrofolate (H4PteGlu), 10-formyltetrahydrofolate (10-HCO-H4PteGlu) and 5 methyltetrahydrofolate (5-CH3-H4-PteGlu) in rat bile by high-performance liquid chromatography with electrochemical detection (HPLC-ECD). After diluting the bile sample with 0.2% sodium ascorbate solution, the sample was analyzed under the following conditions; (a) phenyl bonded phase column as an analytical column; (b) mobile phase consisting of 20 mM acetate buffer (pH 5.0) containing 0.1 mM EDTA; (c) an applied ECD potential of +300 mV; (d) 0.8 ml/min of flow rate. Under the above conditions, peaks of H4PteGlu, 10-HCO-H4PteGlu and 5-CH3-H4PteGlu in rat bile were well separated on the ECD-chromatogram. Detection limits of H4PteGlu, 10-HCO-H4PteGlu and 5-CH3-H4PteGlu were 0.13, 0.11 and 0.10 ng/ml, respectively, at S/N = 3. Bile excretion rates for H4PteGlu, 10-HCO-H4PteGlu and 5-CH3 H4PteGlu, which were analyzed by this method in rats, were 314 +/- 181, 321 +/- 179 and 449 +/- 198 ng/hr, respectively. Bile concentrations of the folates were more than 5,000 times higher than the detection limits for this method. This HPLC ECD method is, therefore, a useful tool for bile folate analysis. PMID- 7999897 TI - Development of Theileria sergenti schizonts in the lymph node of experimentally infected cattle. AB - Schizogony of Japanese Theileria sergenti of cattle was studied by light and electron microscopy. Schizonts were detected in the draining lymph node between 4 and 8 days after sporozoite inoculation. Macroschizonts (the phase of nuclear division having invaginations) were formed 6 days after inoculation. Subsequently, microschizonts (the phase of merozoite formation displaying rosette like appearance) were observed 8 days after inoculation. Multiple infections of a host cell with sporozoites were suggested to occur since different stages of schizonts were simultaneously detected in the same cell. Host cells of schizonts were considerably enlarged by parasitism. However, morphological characteristics of the developmental stages of T. sergenti schizonts resembled those of malignant Theileria species (e.g. T. parva). Schizogony of T. sergenti observed in this study seems to be the primary generation. PMID- 7999898 TI - Parasitic females of Strongyloides papillosus as a pathogenetic stage for sudden cardiac death in infected lambs. AB - The present study was aimed at elucidating the responsibility of parasitic females for sudden cardiac death following Strongyloides papillosus infection in calves. A preliminary experiment demonstrated a percutaneous infection with S. papillosus infective larvae to cause sudden cardiac death in lambs as in calves, indicating lambs could serve as a model to study fatal stronglyloidiasis in calves. Parasitic females of S. papillosus were inoculated into the duodenum of lambs. Lambs given live worms developed continuous sinus tachycardia immediately after inoculation, and died of sudden cardiac arrest by ventricular fibrillation through a phase of the disease identical to the case of percutaneous larval infection. The lambs had high fecal egg counts at the time of death. Inoculation of homogenized worms did not produce fatal arrhythmias. These results demonstrate that live parasitic females of S. papillosus in the small intestine are responsible for cardiac dysfunction regardless of the presence or absence of migratory larvae. PMID- 7999899 TI - Intrauterine transplantation of isogenic pancreatic islets in experimental diabetic rats. AB - The effect of intrauterine transplantation (IU group) as a potential immunologically privileged site on the diabetic state of the recipient was compared with that of conventional intraperitoneal transplantation (IP group) using Fisher 344 rats. Islets were isolated from the pancreata of normal rats and transplanted into the uterus and peritoneal cavity of the isogenic rats with experimental diabetes, which were treated with estradiol benzoate and progesterone. Although all the rats in both groups became normoglycemic within 4 days after transplantation, all of those in the IU group relapsed into a diabetic state up to the 20th day after transplantation. On the other hand, 6 of 8 rats in the IP group remained normoglycemic throughout the experimental period. Weight gain and diminution of urinary glucose excretion in the IU group were significantly lower than those in the IP group (P < 0.01). The glycosylated hemoglobin level in the IU group did not differ significantly from that in the IP group, but the serum level of fructosamine in the IU group was significantly higher than that in the IP group (P < 0.01). These results indicate that the response to fluctuations of blood glucose of islets in the uterine cavity is less than that of islets in the peritoneal cavity. Histologically, islets were observed to be aggregated in the uterine cavity, however the number of cells decreased markedly with time. Although this study demonstrated that blood glucose was normalized by transplantation of islets into the uterine cavity of diabetic rats, long-term survival of the islets in this location was not obtained. PMID- 7999900 TI - Interferon-gamma production of mitogen stimulated peripheral lymphocytes in perinatal cows. AB - The production of interferon-gamma (IFN-gamma) in bovine peripheral blood mononuclear cells (PBMC) during the perinatal period was studied. IFN-gamma activity was neutralized with monoclonal antibodies (MoAb) to recombinant bovine IFN-gamma. IFN-gamma production was apparently suppressed by treatment of the PBMC with MoAb to bovine pan-T cell. IFN-gamma was more susceptible to treatment with MoAb to CD4+ than that with MoAb to bovine CD8+, suggesting that the CD4+ T cell subset was the major producer of the lymphokine formed in the culture. IFN gamma production by concanavalin A (Con A) stimulation was found to be significantly depressed throughout the perinatal period (from 5 weeks before to 7 weeks after parturition) when compared to that of the non-pregnant control group, but phytohemagglutinin (PHA)-induced IFN-gamma production was markedly depressed from 3 weeks before to 2 weeks after calving. The addition of recombinant human interleukin 2 (100 IU/ml) to the PBMC cultures from perinatal cows resulted in the augmentation of IFN-gamma production by stimulation with Con A or PHA. PMID- 7999901 TI - The reduction of humeral fracture in pigeons with intramedullary poly (methyl methacrylate) and neutralization plate fixation. AB - The reduction of experimental humeral fracture in pigeons was performed with intramedullary bone cement (poly (methyl methacrylate): PMMA) and neutralization plate fixation to investigate the effect on bone fracture healing and the recovery of flying ability. As a result, neither plate nor bone cement fixation held for more than 2 weeks, but not refracture was observed in any cases with both plate and bone cement. In the latter group, it was confirmed by flight tests that almost normal flying ability was recovered in 6 weeks. In pathological findings, blood supply to the fractured ends recovered within 2 weeks and no cortical bone necrosis was observed at the time except for a disturbance of endosteal callus formation. The process of fracture healing on the plate side took place slightly later than that on the non-plate side, and when much PMMA remained between the fractured ends of the cortical bone the bone formation became spongioid. In view of the quick recovery of flying ability, however, plate and bone cement fixation is considered appropriate to prevent the displacement of a humeral fracture in the pigeon. PMID- 7999902 TI - Canine splenic hemangiosarcoma with abdominal dissemination. AB - Disseminated hemangiosarcoma was encountered in a 12-year-old female Maltese dog. Tumor tissues were dispersed on the serosal surface of the liver, kidney, digestive tract, omentum and diaphragm. Metastatic lesions were not observed in the parenchyma of the lung and heart. The spleen was enlarged with rupture at the anterior region of the hilus. The disseminated protruding tumor masses could be easily peeled off from the organ surfaces. The tumor cells were round or spindle in shape, with hyperchromatic nuclei containing prominent nucleoli. Various-sized vascular spaces containing erythrocytes and serum could be identified in this tumor. This case was diagnosed as hemangiosarcoma originating from the spleen with abdominal dissemination. PMID- 7999903 TI - Elevated erythrocyte-bound IgG value in dogs with clinical Babesia gibsoni infection. AB - Erythrocyte (RBC)-bound IgG values (IgG concentration, ng/ml) were examined in 8 Babesia gibsoni-infected and 10 healthy dogs by a competitive enzyme immunoassay. Five dogs with clinical B. gibsoni infection, manifesting severe anemia, were observed to have increased RBC-bound IgG values compared to dogs with subclinical B. gibsoni infection and healthy controls, this suggesting that anemia in B. gibsoni infection may be explained in part on the basis of a humoral immunologic mechanism. PMID- 7999905 TI - Specular microscopy of corneal endothelial cells in cynomolgus monkeys. AB - The corneal endothelia of 15 male and 16 female cynomolgus monkeys (estimated age: 2 years and more) were examined with a contact-type specular microscope under general anesthesia. The specular microscopy showed uniform-sized, hexagonal endothelia arranged regularly on the innermost layer of the cornea. Concerning the cell density (cells/mm2), no statistically significant difference was observed between the left and right eyes or between sexes. However, the cell density decreased in monkeys over 7 years old. PMID- 7999904 TI - Chitin and chitosan induce migration of bovine polymorphonuclear cells. PMID- 7999906 TI - Primary splenic lymphoma in a horse. AB - A well-demarcated solitary splenic mass (20 x 20 x 15 cm in size) containing hemorrhagic and necrotic foci was observed in a 4-year-old Thoroughbred stallion. Histologically, the mass consisted of lymphoma cells of the diffuse large non cleaved type, with a high mitotic index and scattered macrophages that formed a starry sky pattern. The lymphoma cells revealed diffuse positivity for acid phosphatase and alpha naphthyl butyrate esterase, and were also positive for intracytoplasmic IgM on occasion, and mostly for proliferating cell nuclear antigen. Ultrastructural examination revealed moderately-developed rough endoplasmic reticulum sometimes with dilated cisternae. Thus, the diagnosis was a primary splenic lymphoma of B cell origin, but the exact reason for the absence of invasive growth or metastasis despite the high proliferative activity of this neoplasm was unclear. PMID- 7999907 TI - Clinicopathological observations on thoroughbred foals with enlarged thyroid gland. AB - Seven cases of thoroughbred foals kept on a farm in the Hidaka district of Hokkaido showed bilateral thyroid enlargement from 3 or 4 months after birth. Their serum T4 levels were remarkably low, whereas T3 levels were in the normal range. Serum T4 levels were also low in the other clinically normal foals and their dams kept together. Since the iodine content in pasture soil and grass was very low, iodine deficiency was supposed to be the cause of the disease. PMID- 7999909 TI - Morphology of spontaneous Harderian gland tumors in aged B6C3F1 mice. AB - Spontaneous Harderian gland tumors in B6C3F1 mice were found in 18 (3.1%) (one male had bilateral tumors) of 589 males and 18 (3.0%) of 609 females. The tumor bearing mice ranged in age from 73 to 109 weeks. These tumors comprised 32 adenomas (86.5%), four adenocarcinomas (10.8%) and one pleomorphic tumor (2.7%); the adenomas were classified, based on the growth patterns, into 17 papillary, nine cystic papillary, five acinar and one cystic types. Two adenocarcinomas grew papillary and invaded surrounding tissues, and the other two grew acinously. The pleomorphic tumor consisted of pleomorphic cells some of which had a keratin positive epithelial feature and acini lined by atypical epithelial cells. PMID- 7999908 TI - Amplification of a c-yes-1-related oncogene in canine lymphoid leukemia. AB - Genomic DNAs from 4 canine spontaneous lymphoid neoplasms were examined by Southern blot hybridization using 7 kinds of oncogene probes. Analysis using a human c-yes-1 cDNA probe revealed amplification of the proto-oncogene in a DNA sample from a dog with lymphoid leukemia. Its degree was about 4- to 8-fold in comparison with a control DNA sample from a healthy dog. The genomic abnormality of canine c-yes-1-related oncogene may have a role in the tumorigenesis of this neoplasm, although the significance of the structural change in this oncogene remains unclear. PMID- 7999910 TI - Prophylactic efficacy of milbemycin oxime against multiple infection of dogs with Dirofilaria immitis. AB - In order to examine the prophylactic effects of milbemycin oxime (MO) against Dirofilaria immitis infection, experiments were carried out under multiple infection with D. immitis. Ten filaria-free beagles of age 4 to 8 months were each inoculated with a total number of 480 larvae 12 times at intervals of 15 days over a period of 6 months, and MO was given monthly for the 6 months at a dose of 0.25 mg/kg. The infection rate in the medicated group of dogs was nil, this suggesting complete protection of the infection, while in the non-medicated control group it ranged from 6.5 to 14.8% (mean, 11.4%). PMID- 7999912 TI - An occurrence of stomach impaction in ostriches (Struthio camelus) on a farm in Zambia associated with high mortality. AB - Fifty-one ostriches (Struthio camelus), 6 weeks old, were imported from Namibia and introduced onto a farm in Zambia. Soon after introduction, most of the birds manifested clinical symptoms such as anorexia and diarrhea and 19 birds died within 1 week. The proventriculus and gizzard in the 4 dead birds were full of solid masses of lucerne hay mixed with maize and consequently the gizzard was extremely impacted by them. Neither pathogenic bacteria nor parasites were detected from the autopsied birds and 8 fecal samples. After diagnosis, the ostrich feed was improved and a demulcent was given immediately; then all ostriches that remained on the farm recovered. In conclusion, these data confirmed that the present case was stomach impaction in ostriches. PMID- 7999911 TI - Plasma ketone levels in neonatal calves fed medium chain triglycerides in milk. AB - Milk fortified with medium chain triglycerides (MCT) was given to neonatal calves to increase their energy intake. Tricaprylin (C8), tricaprin (C10), a mixture of C8 and C10 (mixed MCT) or soya oil were given at 11-18 days of age. Feeding C8, C10, and mixed MCT caused a transient hyperketonemia (3-HB, acetoacetate). Plasma ketone levels returned to the initial ones within 3 hr at 40 or 80 ml of mixed MCT feeding, though hyperketonemia was marked and more persistent at 120 ml dose in one meal. Hyperketonemia caused by C8 was stronger than those caused by C10. Soya oil caused no increase in plasma ketone levels. PMID- 7999913 TI - Isolation of Yersinia pseudotuberculosis from city-living crows captured in a zoo. AB - To study the distribution of pathogenic Yersinia in city-living birds, 145 wild jungle crows were captured in a zoo between June, 1992 and April, 1993. Although pathogenic Yersinia enterocolitica was not isolated, Y. pseudotuberculosis belonging to serovar 4b was independently isolated from 7 caecal contents, respectively. All 7 isolates were positive on temperature-dependent autoagglutination and had a 70 Kb large plasmid. The plasmid DNAs from the 7 strains had the same BamHI digestion pattern. These results suggest that the wild crows in a zoo are one of the possible reservoirs of Yersinia. PMID- 7999914 TI - Immunological cross-reactivity of mannan-binding proteins in bovine, chicken, and human sera. AB - Immunological cross-reactivity of bovine, chicken and human serum mannan-binding proteins was studied by sandwich enzyme-linked immunosorbent assay. Although some immunological cross-reactivity was observed with whole sera as antigens, almost no cross-reactivity was found with purified mannan-binding proteins. Such cross reactivity was found to be due to nonspecific reaction since these animal and human sera reacted with preimmune (or normal) rabbit IgG. From these findings, bovine and chicken sera are suggested to contain human rheumatoid factor-like substance(s) reactive with normal rabbit IgG. Thus, it seems to be necessary to compensate nonspecific reactivity of preimmune rabbit IgG with whole sera for determination of crude mannan-binding proteins. PMID- 7999915 TI - Usefulness of computed tomography after myelography for surgery on dogs with cervical intervertebral disc protrusion. AB - Computed tomography after myelography (CTM) was performed pre- and postoperatively on four dogs diagnosed as having cervical intervertebral disc protrusion. The surgery was performed by ventral slot technique in all the cases. The direction of the ventral slot was precisely adjusted according to the location of the protruded discs as seen on CTM. Postoperative values for the transversal area of the spinal cord were greater than those measured preoperatively, suggesting effective decompression of the cord. The prognosis for these patients was excellent. In view of these results, it was considered that preoperative confirmation of the positional relationship between the spinal cord and the protruded disc by CTM was quite useful in planning the surgical technique for disc disease in the dog. PMID- 7999916 TI - Tissue residues of sulfadimethoxine following dietary administration to broiler chickens. AB - Broilers were divided into four groups and the first group served as the control. The second, third and fourth groups were given feed containing 25, 50 and 100 mg/kg of sulfadimethoxine (SDM), respectively, for 21 days, and thereafter each group received the SDM free feed. On certain days during the experiment period, three broilers in each group were sacrificed and tissues, including blood, heart, liver, spleen, gizzard, thigh muscle, breast muscle and fat, were collected and residual SDM were determined by HPLC. Two days after withdrawal, SDM in each tissue had decreased to below the detection limit of 0.01 microgram/g. PMID- 7999918 TI - Protective immunity against multiple challenges of Brugia pahangi in Mongolian gerbils induced by drug-abbreviated infection. AB - Protective immunity against multiple challenge infections was examined in Mongolian gerbils after a drug-abbreviated infection with Brugia pahangi. The gerbils treated with mebendazole (MBZ) during the late prepatent period (7-9 weeks of postinfection) were challenged with 5 inoculations of 50 infective larvae of B. pahangi at 4-week intervals. The worm burden was significantly reduced 68.6% (19.0 in average number) to that of controls (60.6) and was accompanied with enhanced eosinophil responses 1 week after each challenge. MBZ treated gerbils suppressed microfilaremia almost completely after the challenge infections. PMID- 7999917 TI - Construction of recombinant infectious laryngotracheitis virus expressing the LacZ gene of E. coli with thymidine kinase gene. AB - We constructed the recombinant infectious laryngotracheitis virus (ILTV), CE strain, containing the LacZ gene of E. coli in the thymidine kinase gene. The growth property of the recombinant virus was almost the same as parental CE strain in chicken embryo fibroblasts. The recombinant CE strain of ILTV could be used as a live vaccine vector. PMID- 7999919 TI - Immunoperoxidase procedures for rapid detection of bovine viral diarrhea-mucosal disease virus antigen. AB - Bovine viral diarrhea-mucosal disease (BVD-MD) virus antigen was detected in bovine fetal muscular cells from sera of 42 cattle persistently infected with noncytopathic BVD-MD virus by the indirect immunoperoxidase procedure (IIP) but not from sera of 100 apparently healthy cattle. These findings agreed with the results obtained by the interference method. Furthermore, BVD-MD virus antigens were detectable in the smears of buffy coats by the IIP procedure and in the formalin-fixed tissue sections by the avidin-biotin-peroxidase complex procedure. These procedures are therefore expected to be useful for rapid detection of BVD MD virus antigen. PMID- 7999920 TI - Computed tomography on renal masses in dogs and cats. AB - Computed tomography (CT) was performed on renal tumors (Wilms' tumor and renal cell carcinoma) and renal cysts in dogs and cats. CT images in renal tumors were well correlated with macroscopic findings, and contrast CT images were quite useful in differentiating tumoral regions from non-tumoral ones. On renal cysts, intravenous pyelography and ultrasonography were as effective as CT images in morphological diagnosis, but CT was considered to be superior for evaluating three-dimensional (3-D) relationships in complicated lesions. PMID- 7999922 TI - Effects of interleukin-4 on antigen-specific antibody synthesis by lymphocytes from old and young adults. AB - The current series of experiments were designed to explore the role of the B cell growth factor, interleukin-4 (IL-4), in the age-related decrease in production of antitetanus toxoid antibody in vitro. Exogenous recombinant IL-4 led to significant suppression of antitetanus toxoid antibody synthesis and numbers of antitetanus toxoid antibody-secreting B cells in cultures from healthy old subjects and healthy young subjects. These effects were most pronounced when IL-4 was present during the early phase of culture. Lymphocytes from old subjects were less sensitive to these effects and produced significantly less IL-4 than did lymphocytes from young controls. The addition of exogenous IL-4 may be inhibiting early activation signals that normally stimulate proliferation of B cells. A decreased sensitivity to the growth-promoting effects of IL-4 may be one of the mechanisms underlying defective specific antibody synthesis in aging. PMID- 7999921 TI - Effects of recombinant human interleukin-6 administration on bone in rhesus monkeys. AB - The role of interleukin-6 in the bone microenvironment is controversial. We studied the effect of recombinant human interleukin-6 (rhIL-6) administration on bone metabolism in 10 adult female rhesus monkeys (age 12-27 years). Monkeys received rhIL-6 (15 micrograms/kg/day) daily by subcutaneous injection for 28 days. Serum alkaline phosphatase, osteocalcin, and 24 h urinary calcium excretion were determined before, during (at weeks 2 and 4), and after (at week 6) treatment. Transilial biopsies (right and left) were obtained before treatment was initiated and just after the final (28th) dose at week 4. The serum alkaline phosphatase significantly increased at 2 and 4 weeks of rhIL-6 administration. Osteocalcin and urinary calcium excretion significantly decreased at week 2. Upon treatment with rhIL-6 significant reductions in OS/BS and Ob.S/BS were observed without changes in other static histomorphometry parameters. The reductions in urinary calcium excretion, serum osteocalcin, and the static bone parameters are consistent with an IL-6 induced reduction in bone formation or turnover. Whether this pharmacologic effect is relevant at the physiologic level remains to be determined. PMID- 7999923 TI - Effects of hypoxia on the cytotoxicity mediated by tumor necrosis factor-alpha. AB - We investigated whether hypoxia (2% O2, approximately 14 mm Hg partial pressure) in comparison to O2 atmospheric pressure (20.9% O2, approximately 140 mm Hg) can affect the cytotoxic effects of tumor necrosis factor-alpha (TNF) on the murine cell line L929. Under hypoxic conditions, L929 cells were significantly less inhibited by TNF treatment, even in the presence of actinomycin D. Moreover, under hypoxic conditions, TNF cytotoxicity was significantly inhibited by glutathione, which has been shown to protect cells against oxidative damage induced by various agents. On the other hand, under aerobic conditions treatment with other antioxidant agents and active species oxygen scavengers, as superoxide dismutase and catalase, did not markedly affect the cytotoxicity of TNF. Since hypoxia occurs normally in most solid tumors, these results are interesting because they suggest a disadvantageous inhibition of the cytotoxic effects of TNF in vivo in hypoxic tissues and confirm that oxygen-dependent metabolic processes or free radicals are required to exert TNF-induced cytotoxicity. PMID- 7999924 TI - Glycoform heterogeneity of porcine interferon-gamma expressed in Sf9 cells. AB - Porcine interferon-gamma (SfPoIFN-gamma) was expressed with high efficiency in Spodoptera frugiperda (Sf9) cells by means of the baculovirus expression system. Up to 10(5) U/ml of antivirally active SfPoIFN-gamma could be tracked down in the culture medium at 64 h postinfection. Three proteins (17, 19, and 21 kDa), which under nondenaturing conditions primarily exist as mutual-dimeric combinations, were purified by immunoaffinity chromatography. Carbohydrate labeling and kinetic deglycosylation studies suggested that the 19- and 21-kDa proteins are N glycosylated variants of a single 17-kDa protein carrying no N-linked sugars, in which one respectively two N-glycosylation sequons are occupied by glycans of 2 kDa. Both the quantitative recovery of SfPoIFN-gamma from a Con A column at 0.2 M methyl-alpha-mannopyranoside and the results of lectin blots, revealing strong affinity of the 19- and 21-kDa species for Galanthus nivalis agglutinin, support the presence of N-glycosidically linked high mannose-type chains in the carbohydrate moiety of SfPoIFN-gamma. Intriguingly, both 19- and 21-kDa glycoforms, but not their sialidase-treated derivatives, showed clear reactivity with the Sambucus nigra and Maackia amurensis agglutinins. These agglutinins specifically recognize sialic acid linked alpha(2-6) and alpha(2-3), respectively, to penultimate galactose residues. Their affinity for the larger glycoforms of PoIFN-gamma suggests that the biosynthetic pathways in Sf9 cells are able to modify oligomannose structures to complex or hybrid glycans. PMID- 7999925 TI - Direct comparison of ELISPOT and ELISA-based assays for detection of individual cytokine-secreting cells. AB - A direct comparison was made between the insoluble ELISPOT, solubilized ELISPOT, and ELISA assays, to detect cytokine secretion by cells, using sterile ELISA plates and commercially available monoclonal antibodies. We evaluated the IL-6 secretion by resident peritoneal macrophages of BALB/c mice and the secretion of IL-2, IL-4, IL-5, and IL-6 by the murine T helper clone, D10.G4.1 cells. Our results demonstrated that ELISPOT can detect cytokine secretion at the single cell level in either adherent or nonadherent cells. The level of detection by ELISPOT was 10 to 200 times more sensitive than ELISA performed on culture supernatants. We also demonstrated that the solubilized ELISPOT can detect cytokine secretion by cells with greater sensitivity than conventional ELISA. These ELISPOT assays can be used to characterize the cytokine secretion pattern of different cell populations in a simple, reproducible, and reliable manner. PMID- 7999926 TI - Development of glycosylated human interleukin-1 alpha, neoglyco IL-1 alpha, coupled with D-mannose dimer: synthesis and biological activities in vitro. AB - Interleukin 1 (IL-1) is a nonglycosylated cytokine with pleiotropic effects on various cell types. In order to investigate the effect of carbohydrate introduction on IL-1 activity and to develop IL-1 with less deleterious effects recombinant human IL-1 alpha was chemically coupled with mannose dimers, alpha-D Man1-6-D-Man[Man2(alpha 1,6)] and alpha-D-Man1-4-D-Man[Man2(alpha 1,4)]. About 5 molecules of mannose dimers were introduced per molecule of IL-1. Anti-IL-1 alpha antibody reacted only weakly with the glycosylated IL-1s. Conversely, antibody against the mannose dimer reacted with only glycosylated IL-1. The effect of glycosylation on IL-1 activity was evaluated by measuring a variety of IL-1 activities in vitro, including proliferative effect on T cells, antiproliferative effect on melanoma cells, stimulatory effect on IL-6 synthesis by melanoma cells, and stimulatory effect on prostaglandin E2 synthesis by fibroblast cells. Glycosylated IL-1s exhibited reduced activities, which were 10-fold to more than several hundred-fold lower than those of the original IL-1 alpha depending upon different aspects of activities addressed. Man2(alpha 1,6)-introduced IL-1 exhibited lower activity than Man2(alpha 1,4)-introduced IL-1. The competitive binding of 125I-IL-1 alpha to mouse T cells with unlabeled IL-1s suggests that the reduced activity of glycosylated IL-1s is due, at least partially, to the decrease of their receptor binding abilities. PMID- 7999927 TI - PASAT performance and the pattern of uptake of 99mTc-exametazime in brain estimated with single photon emission tomography. AB - The effect of the paced auditory serial addition test (PASAT) on the regional uptake of 99mTc-exametazime was determined by single photon emission computed tomography. Twenty insulin-treated diabetic outpatients were scanned at rest and during the performance of the PASAT task using split-dose injection of tracer. When resting and activation scans were compared there were significant decreases in tracer uptake in the right anterior cingulate and left posterior cingulate areas during PASAT activation. The findings are compared with previous studies which had implicated the anterior cingulate area in the mechanisms of attention in humans and other animals. The potentially confounding role of anxiety during attentional tasks is discussed. PMID- 7999929 TI - Motor and non-motor aspects of slow brain potentials. AB - In order to study motor and non-motor aspects of the contingent negative variation (CNV), fifteen right-handed subjects were asked to perform tightly controlled responses in a WS-S1-S2 paradigm. WS was a non-informative warning signal; S1 and S2 provided information about the response required at S2. This information was either delivered before a block of trials (Simple), at S1 (Precued), or at S2 (Choice). Negativity was larger prior to the informative than to the non-informative stimulus, suggesting the presence of a component called stimulus-preceding negativity (SPN). This finding supported the hypothesis that the late CNV consists of a readiness potential and an SPN. The scalp distribution of the SPN was different before S1 and before S2. The significance of these components is discussed in terms of motor preparation, stimulus anticipation and energetical processes. PMID- 7999928 TI - The effect of repeated prepulse-blink reflex trials on blink reflex modulation at short lead intervals. AB - The amplitude of a blink reflex is inhibited if the reflex eliciting stimulus is preceded by a short prestimulus (e.g. < 250 ms). If the prestimulus duration is longer than 1 s, blink reflex amplitude is facilitated. The present study investigated the effect of repeated presentations of prestimulus-blink eliciting stimulus pairings on blink reflex modulation. Subjects in Experiment 1 (N = 59) were presented with a sequence of 12 blocks of 7 trials. Within each block, one trial was a blink stimulus alone, whereas the blink stimulus was preceded by a prestimulus on the other trials. Prestimulus intervals were 30, 60, 120, 240, 500 and 2000 ms. Prestimuli were presented continuously throughout the prepulse interval. The amount of reflex magnitude inhibition at the 60, 120, 240 and 500 ms lead intervals and reflex latency shortening at 30 and 60 ms decreased over blocks. The amount of reflex facilitation at a lead interval of 2000 ms was not reduced. In Experiment 2 (N = 22), two groups of subjects were presented with a sequence of blink stimulus alone presentations and prestimulus-blink stimulus pairings. The prestimulus lasted for 120 ms in one group and for 200 ms in the second. Blink reflex magnitude inhibition declined in both groups over blocks of trials. However, the groups also differed in responding on the blink stimulus alone control trials. Experiment 3 (N = 24) employed the same design as did Experiment 2. No difference in control responding was found. Similar to Experiment 2, blink inhibition decreased over repeated trials in both groups. The present results indicate that prepulse inhibition reflects a process which is affected by repeated presentation of prestimulus-reflex stimulus pairings. However, the conclusion that the reduction of prestimulus effects reflects habituation seems to be premature. PMID- 7999931 TI - Strongly focused attention and auditory event-related potentials. AB - Effects of selective attention on the auditory event-related potential were studied by delivering two tones in a rapid, randomized sequence. One of the tones was designated as relevant and the other as irrelevant, the subject's task being to discriminate occasional softer tones within the relevant tones. Relevant and irrelevant tones differed from each other either in location (left vs. right ear) or pitch (300 vs. 6000 Hz). In both conditions, relevant tones elicited a larger N1 deflection (peak latency about 120 ms) than did irrelevant tones. In contrast to the exogenous N1 elicited by unattended tones, the scalp distribution of this attentional "N1 effect" did not depend on the stimulated ear and, further, its amplitude was not affected by the frequency of attended tones. These results suggest that the present attention effect was caused, at least mainly, by an endogenous processing negativity rather than by an enhancement of exogenous N1 components. PMID- 7999930 TI - Effects of carbohydrate and protein meals on cardiovascular levels and reactivity. AB - This study examined the effects of standard laboratory stressors on cardiovascular measures before and after the consumption of a modest meal. A mental arithmetic task and a reaction time task were administered before and 2 h after a carbohydrate or a protein meal. A noncaloric placebo meal and a fasting condition were included as control treatments. The caloric meals, in particular the carbohydrate meal, induced an increase in cardiac output, ventricular contractility, and systolic blood pressure. Total peripheral resistance and diastolic blood pressure dropped. Although postprandial adjustments were substantial, stress reactivity patterns generally were not perturbed by the meals. Only heart rate reactivity was stronger after eating the carbohydrate meal. It is concluded that subjects' meal consumption prior to their participation in a psychophysiological experiment needs to be taken into account. PMID- 7999932 TI - [Does the EEG have a contribution in determining the depth of anesthesia?]. PMID- 7999933 TI - [Perioperative EEG monitoring: studies of the electrophysiological arousal mechanism]. AB - Electroencephalogram recordings have been advocated for assessment of changes in cerebral function during anaesthesia. Controversy exists on the specificity of EEG parameters indicating depth of anaesthesia, because cortical electrical activity is modulated not only by drugs but also by a variety of exogenous and endogenous stimuli. In clinical practice, EEG measures often fail to accurately predict anaesthetic depth since the effects of nociceptive stimulation on the EEG are still not well defined. Previous reports indicate that in anaesthetised patients sensory stimulation may induce a shift to a dominant EEG frequency with faster waves similar to patterns seen during emergence from anaesthesia under certain circumstances. This electrophysiological arousal (EEG desynchronisation) may be associated with clinical arousal phenomena such as movement and increases in haemodynamic and respiratory activity. However, the mechanism of arousal during emergence from anaesthesia may be quite different from arousal reactions induced by noxious stimulation. Recent studies indicate that surgical stimulation can induce increases in slow wave EEG-activity ("reverse" or "paradoxical" arousal) associated with clinical arousal phenomena. Stimulus related delta patterns also were observed after acoustical or painful stimulation in head injured patients. The occurrence of slow EEG wave patterns may be related to functional blockade of the ascending activating system of the brain stem. In contrast, slowing of the EEG is comparable to EEG changes seen with increasing concentrations of anaesthetics. This indicates the difficulty to discriminate arousal phenomena from drug effects using EEG monitoring alone.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7999934 TI - [Topographic changes in cerebral electric activity after premedication with flunitrazepam]. AB - AIM: The effects on cerebral function of premedication with the benzodiazepine flunitrazepam and with morphine were studied on the evening of the preoperative day (2 mg flunitrazepam p.o.) and 90 minutes before induction of anaesthesia (2 mg flunitrazepam plus 15 mg morphine i.m.). DESIGN: The EEG was analysed topographically (17 electrodes) and quantitatively. RESULTS: As a typical effect of benzodiazepines, increases in electrical activity in the frequency band beta-1 of the power spectrum were observed, and could be demonstrated 10 minutes after oral application, mainly in the frontal and central parts of the cortex. Increases in the powerbands delta and theta indicated induction of sleep approximately 15-20 minutes after application and were not looked upon as an effect of the benzodiazepine exclusively. These increases were noticed first in the central, occipital and temporal areas and after 30 minutes in the frontal parts of the cortex. Flunitrazepam plus morphine showed qualitatively similar but quantitatively less pronounced results. Topographical differences were similar to the results of an application of flunitrazepam alone. DISCUSSION: The results demonstrate the importance of a topographical as well as quantitative evaluation in studies on complex interactions of sedative or narcotic drugs and their clinical effects on cerebral function. PMID- 7999935 TI - [Dose-response relationship of atracurium in underweight, normal and overweight patients]. AB - OBJECTIVE: In patients with extreme stature or build, estimation of individual dosage requirements of muscle relaxants by body weight is unreliable. To define a more precise guideline for dosage of atracurium in clinical practice we compared in this prospective study in patients with a wide range of body weights the cumulative effective dose for a 95% twitch depression (ED95), the dosage necessary to maintain a 95% twitch depression (DD95) and the recovery from a 95% neuromuscular block with simple demographic data such as body weight, body size, body surface area and lean body mass (LBM). METHODS: 30 patients were divided into three groups according to the individual body weight: underweight, normal, overweight. The electromyographic response was monitored using train-of-four stimuli applied to the ulnar nerve. Neuromuscular block was induced by constant infusion of atracurium; the dose required for a 95% twitch depression was registered as ED95. The infusion rate was then adjusted to maintain a constant electromyographic response of the first twitch of 5 +/- 1% for at least 30 minutes and the required dose of atracurium was recorded as DD95. The neuromuscular recovery was studied regarding T1 and T4-ratio. Data are given as medians (25%-/75%-quartiles). RESULTS AND DISCUSSION: The cumulative ED95 in underweight patients (0.34 (0.31/0.48) mg/kg) exceeded (P < 0.05) those in normal (0.29 (0.26/0.30) mg/kg) and in overweight patients (0.22 (0.18/0.26) mg/kg). In contrast to calculations according to the normal weight (Mn) no difference in ED95 was seen between groups (normal: 0.29 (0.26/0.30) mg/kg Mn; underweight: 0.28 (0.26/0.32) mg/kg Mn; overweight: 0.31 (0.25/0.32) mg/kg Mn). The individual DD95 was best correlated with LBM (r = 0.465, p < 0.01). In view of the difficulty of estimating LBM in routine clinical practice it is emphasized that DD95 correlates only slightly less with normal weight (r = 0.404, p < 0.05). In spite of the variability of DD95 with regard to body weight, the recovery of neuromuscular transmission in the patients of the three groups is comparable. As a constant neuromuscular block cannot be maintained without monitoring muscular evoked responses, even if body build is taken into account, neuromuscular monitoring is advocated for longer infusion of atracurium. PMID- 7999936 TI - [Anesthesia standards: factors or fiction? II]. PMID- 7999937 TI - [In children with upper respiratory tract infection the risk of anesthesia is increased--fact or fiction?]. PMID- 7999938 TI - [Stimulation of diuresis prevents renal failure--fact or fiction?]. PMID- 7999940 TI - [The pulmonary capillary wedge pressure reflects the preload of the left ventricle--fact or fiction?]. PMID- 7999939 TI - [General anesthesia with high fresh gas flow is safer than "minimal flow"--fact or fiction?]. PMID- 7999941 TI - [Preoperative roentgen image of the thorax increases anesthesia safety--fact or fiction?]. PMID- 7999942 TI - [Autologous blood is saver than donated blood--fact or fiction?]. PMID- 7999943 TI - [Peridural morphine administration in restless legs status]. AB - The restless-legs syndrome is known to occur in a familial form. The paraesthesias, which are hard to define, are sometimes compared to a painful sensation that can be alleviated only by movement. The pathomechanism of the syndrome and its aetiology are still unknown. A 67-year old patient was admitted as an emergency with most severe pain in her legs. In her family the syndrome occurred in an autosomal dominant form. A long-standing history of abuse of various analgesics was known. Initially the symptoms could not be influenced by any of the various drugs given; even epidural bupivacaine showed no effect. Dramatic relief, however, was obtained by epidural morphine. The maintenance therapy with oral morphine sulfate provided equally good results. PMID- 7999944 TI - [Cervical epidural infusion of morphine and bupivacaine in severe erythromelalgia]. AB - A 13 year old boy was admitted suffering from severe burning pain in both hands and distal forearms of two months duration. The skin in the affected areas was red and warm and was cooled by the boy with ice for alleviation of pain. Laboratory tests revealed no abnormalities. The diagnosis of primary erythromelalgia was made on the basis of the history and physical examination. At the age of nine months the boy had undergone surgery for hexadactyly of the right hand. In addition, the boy had complained of transient burning sensations in both feet several months prior to admission. Revision of the old scar at the beginning of the hand symptoms had been without effect. Initial analgesic attempts with oral paracetamol, acetylsalicylic acid, tramadol and intravenous morphine also had had no effect. Carbamazepine, methysergide and immunoglobulins led to no improvement. Symptomatic relief was achieved only by cooling the distal parts of both arms with water. This caused oedema and maceration of the skin after several days. The placement of a cervical epidural catheter and the infusion of morphine and bupivacaine led to a pronounced pain relief within hours and the forearms could be removed from the cool water. The epidural infusion was continued for two weeks with slowly decreasing amounts of morphine and bupivacaine. During this time there was a marked improvement in both oedema and erythema. No complications resulted from the cervical epidural infusion. Because of the long-standing immobilisation and water exposure the boy had to undergo intensive training of the upper extremities during the following weeks to regain full muscular function.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7999946 TI - [Report on the "21st Neonatal and Infant Respiratory Symposium" in Vail, Colorado, 27 March to 1 April 1994]. PMID- 7999945 TI - [Diagnostic and intensive care problems in hemolytic uremic syndrome]. AB - We observed a young man with apparently septic appendicitis who finally could be diagnosed as suffering from haemolytic uraemic syndrome (HUS) when spuriously normalising platelet counts were identified as a cell counter artifact. This case stresses the fact that automatically counted abnormal thrombocyte numbers should be examined by microscopy. Therapy is empirically based on corticosteroids, plasmapheresis and fresh frozen plasma. The application of thrombocyte concentrates should be avoided because of the risk of aggravating the disease process. PMID- 7999947 TI - The fundamental theorem of natural selection. PMID- 7999948 TI - Composition and cariogenic potential of dental plaque fluid. AB - Our understanding of the chemical events that take place at the tooth-plaque interface has improved greatly through studies of the chemical composition and properties of dental plaque fluid. In the absence of fermentable carbohydrate, plaque fluid has been found to be supersaturated with respect to tooth mineral and other calcium phosphate phases, thus exhibiting the potential to support calculus formation and the remineralization of incipient carious lesions. Following the exposure to fermentable carbohydrate, the degree of saturation of plaque fluid decreases rapidly, primarily due to lactic acid production and the lowering of plaque fluid pH. The extent of these chemical changes has been shown to be associated with differences in caries history. Such studies have been facilitated by the recent development of microanalytical techniques. Unfortunately, little is known about the relationship between the observed chemical changes in plaque fluid and the microbial composition of plaque. Limited information is also available on the association of immune factors in plaque fluid with dental disease. PMID- 7999949 TI - Sex steroid hormones and cell dynamics in the periodontium. AB - The biological changes that occur in tissues of the periodontium during puberty, the menstrual cycle, pregnancy, menopause, and oral contraceptive use have heightened interest in the relationship between sex steroid hormones and periodontal health. These clinical observations coupled with tissue specificity of hormone localization, identification of hormone receptors, as well as the metabolism of hormones have strongly suggested that periodontal tissues are targets for androgens, estrogens, and progestins. The etiologies of periodontal endocrinopathies are diverse; nonetheless, periodontal pathologies may be a consequence of the actions and interactions of sex steroid hormones on specific cells found in the periodontium. PMID- 7999950 TI - Internal organization in the human jaw muscles. AB - The human jaw muscles are essential to mastication and play an important part in craniofacial growth. They contribute to dental and articular forces, deform the mandible, and, like other tissues, are subject to disorders, often manifested as pain. The literature describes how their contraction is controlled by the nervous system, and how their general structure and function contribute to craniofacial biology, but there has been little appraisal of their internal organization. Most of these muscles are not simple; they are multipennate, complexly layered, and divided by aponeuroses. This arrangement provides substantial means for differential contraction. In many ways, jaw muscle fibers are intrinsically dissimilar from those found in other skeletal muscles, because they are arranged in homogeneous clusters and generally reveal type I or type II histochemical profiles. Most are type I and are distributed preferentially in the anterior and deeper parts of the jaw closers. Additionally, most motor unit (MU) territories are smaller than those in the limbs. There is circumstantial evidence for intramuscular partitioning based in part on innervation by primary muscle nerve branches. During normal function. MU recruitment and the rate coding of MU firing in human jaw muscles follow the general principles established for the limbs, but even here they differ in important respects. Jaw muscle MUs do not have stable force recruitment thresholds and seem to rely more on rate coding than on sequential unit recruitment to grade the amplitude of muscle contraction. Unlike those in the limbs, their twitch tensions correlate weakly with MU fatiguability and contraction speed, probably because there are so few slow, fatigue-resistant MUs in the jaw muscles. Moreover, the type I fibers that are present in such large numbers do not contract as slowly as normally expected. To complicate matters, estimation of jaw MU twitch tensions is extremely difficult, because it is affected by the location used to measure the twitch, the background firing rate, muscle coactivation, and regional, intramuscular mechanics. Finally, there have been very few systematic studies of jaw MU reflex behavior. The most recent have concentrated on exteroceptive suppression and suggest that MU inhibition following intra- and perioral stimulation depends on the location of the MU, its background firing rate, the timing of the stimulus, and the task used to drive the unit. Task dependency is a common feature of human jaw MU behavior, reflecting interaction between peripheral sensory information from orofacial and muscle afferents and corticobulbar drive.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 7999951 TI - The preferential expression of the anti-DNA associated 8.12 idiotype in lupus is not genetically controlled. AB - Anti-DNA antibodies are autoantibodies unique to systemic lupus erythematosus. Studies of their structure have demonstrated cross reactive idiotypes present in genetically unrelated individuals. Despite much research, it is still not clear what triggers their production and what governs the presence of particular idiotypic determinants in their structure. To study the role of genetic and environmental factors in the expression of idiotype, we analyzed sera of SLE patients, their family members and nonautoimmune individuals vaccinated with pneumococcal polysaccharide, for the presence of the 8.12 idiotype, which is present on lambda light chains of anti-DNA antibodies. Elevated titers of the 8.12 idiotype was found in the serum of 57% of SLE patients. Elevated titers were present in only 9% of family members, and always associated with the presence of high levels of IgG anti-DNA antibodies. Following vaccination with pneumococcal polysaccharide, 8.12 reactive anti-pneumococcal antibodies were produced by 7 of 10 non-autoimmune individuals and 8.12 reactive anti-DNA antibodies by one. These results suggest that 8.12 reactive antibodies are antigen driven and bind structurally related antigens, but there is no evidence that expression of this idiotype is genetically controlled. PMID- 7999952 TI - Loss of RT6 message and most circulating T cells after thymectomy of diabetes prone BB rats. AB - T cells expressing the RT6 surface alloantigen perform important immunoregulatory functions in the rat. Diabetes prone (DP) BB rats are deficient in circulating RT6+ T cells and develop spontaneous autoimmune diabetes mellitus. Transfusions leading to engraftment of RT6+ T cells prevent the disease. Coisogenic diabetes resistant (DR) BB rats do circulate RT6+ T cells and are free of disease. We investigated the basis for the deficiency of RT6+ T cells in the DP-BB rat and made the following observations. 1. Thymectomy causes the rapid loss of most peripheral T cells in the DP-BB rat. 2. Concomitant with the loss of T cells is the total loss of mRNA encoding RT6. 3. In contrast to the effects observed in peripheral lymphoid tissues, thymectomy does not lead to a detectable loss in RT6+ protein found in the small intestine. We conclude that the deficiency of RT6+ peripheral T cells in the DP-BB rat is due either to their short life span or to their reduced proliferative capacity following release from the thymus. PMID- 7999953 TI - Effect of cepharanthin and cytochalasin D on platelet internalization of anti glycoprotein IIb/IIIa antibodies. AB - The effects of cepharanthin and cytochalasin D on the internalization of anti glycoprotein IIb/IIIa antibodies by platelets were investigated in 13 patients with chronic immune thrombocytopenic purpura who had circulating anti glycoprotein IIb/IIIa autoantibodies. Unfixed platelets were incubated with a monoclonal anti-glycoprotein IIb/IIIa antibody (NNKY1-32) or with platelet binding IgG from the patients (which contained anti-glycoprotein IIb/IIIa antibodies). Flow cytometry showed that the binding of NNKY1-32 to platelets was markedly decreased after incubation for 120 min compared with incubation for 10 min. This decrease was inhibited by cepharanthin but not by cytochalasin D. Platelet-binding IgG also showed markedly reduced binding after incubation for 120 min compared with 10 min, and this decrease was inhibited by both cepharanthin and cytochalasin D. Cytochalasin D inhibits platelet cytoskeletal activity while cepharanthin does not. Therefore, our results suggest that the internalization of anti-glycoprotein IIb/IIIa antibodies from the plasma of patients with immune thrombocytopenic purpura is related to platelet cytoskeletal reorganization, while the cytoskeleton did not participate in internalization of the monoclonal anti-glycoprotein IIb/IIIa antibody (NNKY1-32). Cepharanthin may be useful for studying the internalization and cycling of glycoprotein IIb/IIIa in human platelets, and it may also be potentially useful for the treatment of immune thrombocytopenic purpura. PMID- 7999954 TI - Iodide induced lymphocytic thyroiditis in the BB/W rat: evidence of direct toxic effects of iodide on thyroid subcellular structure. AB - A high dietary iodine intake accelerates the development of lymphocytic thyroiditis (LT) in the BB/W rat. Our previous studies have defined the temporal sequence of the immunological events triggered by excess iodide intake in these animals. It was still not clear, however, whether these observed immunological changes were a direct effect on immune effector cells, or whether they represented a secondary response to a toxic effect of iodine on thyroid tissue. In the present study, the effect of excessive iodine intake on the subcellular structure of the BB/W rat thyroid gland, particularly, whether iodide had a toxic effect independent of its immune response has been examined. BB/W rats were exposed, prenatally through maternal drinking water, to excessive iodide at two doses (Moderate 3 x 10(-6) M iodide/l; High 3 x 10(-3) M iodide/l); a third group of BB/W rats was given tap water; till 12 weeks postnatal age. Two groups of Wistar rats received high dose iodide water or tap water for the same period of time and served as controls. Thyroid gland ultrastructure was determined by electron microscopic (EM) examination. Thyroid 125I uptake and perchlorate discharge tests were also performed in separate experiments. We found that thyroid glands of non-iodine supplemented Wistar rats were morphlogically normal under EM. There were no overt changes in the iodide treated Wistar rats. By contrast, iodide treated BB/W rats exhibited marked accumulation of secondary lysosomes and lipid droplets; markedly swollen and disrupted mitochondria and extreme dilatation of rough endoplasmic reticulum (RER).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7999955 TI - Antiphospholipid antibodies in patients with idiopathic autoimmune haemolytic anemia. AB - Isolated cases of anti-phospholipid antibody (aPL)-associated idiopathic autoimmune haemolytic anemia (IAHA) have been recently described. To assess the significances of this association, we studied by ELISA the presence of aPL in sera from 18 patients with IAHA and 14 patients with non-autoimmune haemolysis (NON-AH). Four IAHA cases and none of the NON-AH controls showed IgM anticardiolipin antibodies (aCL) that crossreacted extensively with zwitterionic as well as with other anionic phospholipids. IgG aCL were detected in 6 patients with IAHA and in 1 patient with NON-AH; there was little cross-reactivity with other phospholipids. Our results suggest that antiphospholipid antibodies are present in a substantial number of patients with IAHA. This humoral response does not seem to be secondary to the haemolysis proper. The potential pathogenic significance of this finding is discussed. PMID- 7999956 TI - Studies of IgG-class anticardiolipin antibodies in myasthenia gravis. AB - IgG-class anticardiolipin antibodies (IgG-ACA) were found in 25% of patients with myasthenia gravis. The prevalence and the level distribution were significantly different from those of a normal donor population (p < 0.001). In myastenic patients, IgG-ACA bound negatively charged, but not zwitterionic, phospholipids. They were significantly associated with the thymic abnormalities, thymoma and thymic hyperplasia, but not with various factors such as age, sex, antinuclear antibodies, severity of the disease and clinical thrombosis. The IgG-ACA levels did not correlate with titers of anti-acetylcholine receptor antibodies. Thus in Myasthenia Gravis, asymptomatic IgG-ACA could reflect an immune dysregulation under the influence of thymic alterations. PMID- 7999957 TI - The role of VL gene structural determinants in the fine specificity of anti-DNA antibodies. AB - To investigate the structural contribution of the light chain of anti-DNA antibodies to fine specificity, the VKappa genes of two monoclonal anti-DNA antibodies, termed H241 and H102, were cloned and sequenced. H102 and H241 are independently derived from MRL-lpr/lpr mice and differ in their fine specificity: H241 binds dsDNA and normal glomeruli in vitro and deposits in the kidney in vivo, whereas H102 binds only ssDNA and does not deposit in the kidney. Both are encoded by nearly identical VH genes but different N and D regions. Our previous results have demonstrated that the VH gene for H102 and H241 encodes eight other anti-DNA antibodies that also differed in fine specificity. This suggested that the gene product encoded by the VH 102/241 gene, may have intrinsic affinity for DNA, but is unlikely to determine fine specificity or nephritogenicity. In the present study we examined whether the VKappa gene might account for the difference in nephritogenicity. The complete nucleotide and deduced amino acid sequence of VK 102 and VK241 revealed that they are very dissimilar to each other (< 60% homology). VK 241 defined a new member of the VKappa gene family and was moderately homologous to two other VK genes encoding anti-DNA antibodies and to one VK gene encoding an anti-histone antibody all from lupus strains of mice. In addition, sequence diversity in the VK CDR1 region and position 96 of the CDR3 region was observed that may be of significance in determining fine specificity. VK 102 was highly homologous to two other VKappa genes, VKs17.2 and VK C8.5, both encoding anti-DNA antibodies and members of the VK20 gene family. It was striking that all three members of the VK 20 gene family code for DNA reactivity. This suggests that certain VKappa genes may also be used to repeatedly code for anti DNA reactivity. PMID- 7999959 TI - Analysis of the peripheral T-cell receptor V beta repertoire in newly diagnosed patients with type I diabetes. AB - Type I diabetes is an autoimmune disease characterised by a marked activation of peripheral T cells around the time of clinical diagnosis. Studies of T-cell antigen receptor V beta (TCRBV) gene usage in type I diabetes have been conflicting. Using a semi-quantitative polymerase chain reaction technique and flow cytometry we have investigated the TCRBV gene usage of 13 newly diagnosed patients with type I diabetes and 11 normal healthy controls. No preferential TCRBV gene usage was found between patients and controls even after matching for HLA-DR3 and/or -DR4. In addition, no significant differences in TCRBV gene usage were found between sequential samples taken over a period of up to 7 months following diagnosis. These results suggest that the TCR repertoire of these patients is heterogeneous and it is unlikely that a single 'pathogenic' T-cell clone is dominant at the clinical onset of the disease. PMID- 7999958 TI - A model to study viral and cytokine involvement in Sjogren's syndrome. AB - To investigate mechanisms that may be important in the pathogenesis of Sjogren's syndrome (SS) we developed a protocol for the growth of salivary gland epithelial cells in culture. We examined the effect that viral infection has on the cellular location of the autoantigen La. Autoantibodies to La are common in SS and it has been proposed that viral infection may result in cell membrane expression of La. Co-expression of MHC class II molecules in infected cells could lead to the presentation of La peptides to the immune system. Advenovirus infection of salivary gland epithelial cells resulted in an altered nuclear staining of La. Treatment with interferon-gamma resulted in the expression of La in the cell cytoplasm and HLA-DR molecules at the cell surface. These findings suggest that a cytokine-driven mechanism may generate an autoimmune response to La in SS. Using the polymerase chain reaction (PCR) we tested salivary gland epithelial cell cultures for the presence of human herpesvirus-6 (HHV-6) and Epstein-Barr virus (EBV). Only HHV-6 was detected in 2 of 10 salivary gland epithelial cell cultures although the presence of HHV-6 was not associated with SS. Primary salivary gland cultures may prove useful as an in vitro model to study mechanisms of autoimmunity in SS. PMID- 7999961 TI - Coffee and cancer: a prospective study of 43,000 Norwegian men and women. AB - Relationships between coffee drinking and cancer incidence were examined in a 10 year complete follow-up of 21,735 men and 21,238 women aged 35-54 years. The study population participated in a cardiovascular screening in three countries in Norway during 1977-82. Data on coffee and smoking habits were based on information from a self-administered questionnaire. There was no association between coffee consumption and overall risk of cancer. A positive association was found between coffee drinking and risk of lung cancer, also after adjustment for age, cigarette smoking, and county of residence. Residual confounding by cigarette smoking and other lifestyle factors cannot be ruled out. A negative association was found with cancer of buccal cavity and pharynx and with malignant melanoma in women. No significant associations were found between coffee drinking and incidence of cancer of the pancreas or the bladder. PMID- 7999960 TI - Dietary cholesterol, fat, and lung cancer incidence among older women: the Iowa Women's Health Study (United States). AB - To test the hypothesis that a high intake of dietary cholesterol and fat is associated with elevated risks of lung cancer, we analyzed data from a population based, prospective, cohort study conducted among 41,837 postmenopausal Iowa (United States) women who completed, in 1986, a comprehensive mailed questionnaire including information on usual intake of 127 food items. All cohort members were followed for cancer incidence through the statewide cancer registry. By 1991, after six years of follow-up, 272 incident lung-cancer cases were identified. After controlling for total energy intake and other confounding factors, dietary cholesterol, total fat, and animal fat were unrelated to lung cancer risk. Intake in the upper three quartiles of plant-derived fat, however, was related to a 30 to 40 percent lower incidence of lung cancer, comparative with those in the lowest quartile, with more pronounced reduction in risk observed among smokers (relative risk = 0.6, 95 percent confidence interval = 0.4 0.9). This prospective cohort study suggests that high intake of fat of plant origin may be associated with reduced risk of lung cancer, while dietary cholesterol and animal fat intake is unrelated to the etiology of this malignancy in postmenopausal women. PMID- 7999962 TI - Prevalence of second generation antibody to hepatitis C virus among voluntary blood donors in Osaka, Japan. AB - To clarify the demographic characteristics of the prevalence of hepatitis C virus (HCV) infection in Osaka, Japan, where hepatocellular carcinoma is common, we investigated the screening data of antibody to HCV (anti-HCV, DAINABOTHCVPHA, second generation assay) in 197,600 voluntary blood donors residing in Osaka. The study found that age-standardized prevalence of anti-HCV was significantly higher than that of HBsAg (2.25 cf 0.86 percent among males, P < 0.001; 2.17 cf 0.55 percent among females, P < 0.001. It was much higher in the blood donors aged 55 64 years than in those aged 16-54 years (8.49 cf 1.32 percent among males, P < 10(-5); 7.26 cf 1.42 percent among females, P < 10(-5)). The prevalence of anti HCV among males was significantly higher than that of females in the younger (25 34 years) generations (1.02 to 1.49 percent cf 0.71 to 1.13 percent, P < 0.05). A similar tendency was observed in the prevalence of high-titer (> or = 2(12)) anti HCV. The number of coinfection (both HBsAg and anti-HCV seropositive) was very small, and it was not statistically different from the expected number. PMID- 7999963 TI - Cancer incidence in migrants to New South Wales (Australia) from the Middle East, 1972-91. AB - The incidence of cancer in migrants to New South Wales (NSW) from Cyprus, Egypt, Iran, Iraq, Israel, Lebanon, Syria, and Turkey has been compared with that in the Australian-born population using data from the NSW Central Cancer Registry for 1972-91. Age-standardized incidence rates showed overall cancer incidence to be less common in migrants from each Middle Eastern country than in the Australian born. There was a clear pattern of generally low rates for cancers of the mouth and pharynx, esophagus, colon and rectum, lung (men only), ovary, prostate and testis, and melanoma. Cancers which tended to be more common in migrants were nasopharynx, stomach (women only), liver (men only), gallbladder (chiefly in women), bladder (men only), and thyroid. Breast cancer did not show a uniform pattern among migrant groups, rates being high in the Egyptian-born but low in Lebanese-born women. The overall low incidence of cancers related to tobacco and alcohol, and to a 'high fat, low fiber' diet, emphasizes the potential role of preventable lifestyle factors in the burden of cancer in Australia. PMID- 7999964 TI - Dietary factors and non-Hodgkin's lymphoma in Nebraska (United States). AB - Little is known about dietary factors and non-Hodgkin's lymphoma (NHL) risk, although high intakes of animal protein and milk have been associated with NHL in two previous studies. As part of a population-based case-control study of agricultural and other risk factors for NHL in eastern Nebraska (USA), we examined the self- and proxy-reported frequency of consumption of 30 food items by 385 White men and women with NHL and 1,432 controls. Animal protein intake was not associated significantly with the risk of NHL, however, there was a nonsignificantly elevated risk of NHL among men with high milk consumption. Vitamin C, carotene, citrus fruit, and dark green vegetable intakes were inversely significantly related to the risk of NHL for men, but not for women. Among men, the odds ratios for the highest quartiles of both vitamin C and carotene intake were 0.6 (95% confidence intervals = 0.3-1.0). There were no meaningful differences in the associations of nutrient intakes and NHL risk between B- and T-cell lymphomas and histologic types. Risks for low intakes of vitamin C and carotene were greater among men and women with a family history of cancer, particularly a history of lymphatic or hematopoietic cancer among first degree relatives. PMID- 7999965 TI - Longchain serum fatty acids and risk of thyroid cancer: a population-based case control study in Norway. AB - Epidemiologic studies have shown an association between seafood consumption and risk of thyroid cancer. Fish meals increase the serum concentrations of the longchain fatty acids, eicosapentaenoic acid (20:5,n-3) (EPA) and docosahexaenoic acid (22:6,n-3) (DHA), for days. The hypothesis that serum concentrations of fatty acids may be associated with thyroid cancer risk therefore was tested in a population-based case-control study with 74 cases and 221 matched controls. Seventy-three cases with sera in the Norwegian serum bank (JANUS) were identified in the Norwegian Cancer Registry and matched with three controls, also in JANUS, on age, gender, place of residence, and time of blood sampling. One [corrected] case was matched with two controls. Serum concentrations of 11 longchain fatty acids were determined blindly by gas chromatography for all subjects. Controls were divided into three groups with increasing serum fatty acid concentrations, and odds ratios between cases and controls were estimated relative to the group with lowest serum level by univariate and multivariate analyses. The main finding was a significant inverse relation between the sum of arachidonic acid (20:4,n-6) (AA) and DHA serum concentrations and thyroid cancer risk. The significance of this association was weakened when the analyses were restricted to the papillary type of thyroid carcinoma. It was of the same order of magnitude whether the period between blood sampling and diagnosis was greater than eight years, or eight or less years. High EPA/AA ratio, indicating consumption of fish fat, was not associated significantly with increased thyroid-cancer risk.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7999966 TI - Cancer survival among American Indians in western Washington State (United States). AB - Cancer survival among American Indians is worse than among other races in some regions of the United States, but has not been studied among American Indians in Washington state. Our purpose was to evaluate cancer survival among American Indians included in the Seattle-Puget Sound Cancer Registry. We compared site specific survival among American Indians (n = 551) and Whites (n = 110,899) diagnosed from 1974 to 1989 for five cancer sites. For all sites except prostate, the distribution of cancer stage at diagnosis for American Indians was not significantly different from the distribution for Whites, and a similar proportion of American Indians and Whites received cancer treatment. After adjustment for age differences between American Indians and Whites, American Indians experienced poorer survival from prostate, breast, cervical, and colorectal cancer. Poorer survival among American Indians persisted after adjustment for differences in cancer stage at diagnosis, lack of cancer treatment, and residence in a non-urban county. The survival experience among American Indians who were recorded as non-American Indians in the cancer registry but who were listed as American Indians in Indian Health Service records was more favorable than that among persons initially coded as American Indians in the cancer registry. We conclude that cancer survival among American Indians in western Washington is poorer than that among Whites in the same region, and that factors other than age, differences in stage at diagnosis, lack of cancer treatment, and residence in non-urban counties account for this. PMID- 7999967 TI - Cancer risks among female farmers in Sweden. AB - There are few studies on cancer risks among female farmers, particularly on breast cancer and cancer in female genital organs. We have conducted a cohort study of cancer risk among 50,682 women with occupations in agriculture according to the Swedish 1970 census. The cohort was followed up in the nationwide, population-based, Cancer-Environment Register from 1 January 1971 until death or until 31 December 1987. Expected number of cases was based on annual cancer incidence in five-year age groups. The standardized incidence ratio (SIR) was computed as the ratio between observed and expected number of cases. A total of 4,474 cases of cancer were observed in the cohort from 1971 until 1987 cf 5,273 expected, resulting in a significantly decreased SIR of 0.85 (95 percent confidence interval [CI] = 0.82-0.87). SIR for breast cancer was significantly decreased (0.83, CI = 0.78-0.88), as was the SIR for cervix uteri (0.40, CI = 0.31-0.50). For the other female genital organs, SIR was close to one. Other cancer sites with significantly decreased SIRs were: colon (0.90, CI = 0.81 1.00); rectum (0.86, CI = 0.74-1.00); lung (0.46, CI = 0.37-0.57); kidney (0.81, CI = 0.68-0.97); urinary organs (0.57, CI = 0.45-0.72); connective tissue and muscle (0.62, CI = 0.39-0.95); and non-Hodgkin's lymphomas (0.78, CI = 0.63 0.96). PMID- 7999969 TI - Pelvic radiotherapy, sex hormones, and breast cancer. AB - Radiotherapy for malignant and benign gynecologic disease in middle age has been found to be associated inversely with the risk of breast cancer in several published studies. The ovaries received substantial doses of radiation from such treatments, in the tens of Gray (Gy) from radiotherapy for cervical cancer and one to 10 Gy from radiotherapy for benign gynecologic disease (BGD). The relative risk of breast cancer incidence or mortality decreased with increasing radiation dose to the ovaries between zero to six Gy but varied little with further increases in dose. Evidence of a protective effect even among women irradiated past the age of 50 suggests a mechanism other than that associated with induction of an early menopause. An inverse association with radiotherapy among women over age 50 was seen only for women with ovarian doses exceeding about four to five Gy, namely, those treated for cervical cancer or with external beam X-rays for BGD. Ovarian doses of two to three Gy from intrauterine radium (226Ra) treatments for BGD were not associated with an appreciably reduced risk of breast cancer, even though the treatments had the intended effect of inducing menopause in women in their mid-40s. The relevant target cells in the ovaries for radiologic menopause likely are those involved in estrogen production. Although the postmenopausal ovary has largely stopped producing estrogens, it continues to secrete androgens. Serum hormone measurements on a small sample of cervical cancer patients indicate that high-dose pelvic radiotherapy eliminates or greatly reduces this residual androgen-producing activity in ovaries of postmenopausal women.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7999968 TI - Familial risk and genetic susceptibility for breast cancer. AB - Clinical observations suggest that breast cancer is occasionally inherited as an autosomal dominant disease in families. Epidemiologic studies consistently have shown that a history of breast cancer in a first-degree relative increases a woman's risk of breast cancer when compared with the general population. The risk is similar if a mother or sister is affected and is increased further if both are affected. The difficulty with such an observation is that in itself it does not clarify the nature of the true underlying risk factors which could be genetic or due to the aggregation of environmental risk factors in families. Complex segregation analysis of breast cancer aggregation in families suggests that breast cancer susceptibility is due to an autosomal dominant inheritance of one or more rare genes in a few families in which carriers have a high probability of developing the disease perhaps as great as 100 percent. Close linkage of a breast cancer-susceptibility gene (BRCA1), between markers of the chromosomal region 17q12-q21 on the long arm of chromosome 17, with breast cancer recently has been reported. Families linked to BRCA1 were more likely to have early onset of breast cancer or have breast and ovarian cancer in the family. It is likely that other genes play a role in the unlinked breast-cancer families. Both the epidemiologic and genetic data suggest that breast cancer is a heterogeneous disease. PMID- 7999971 TI - Cured meats and childhood cancer. PMID- 7999970 TI - Obesity and multiple myeloma. AB - An exploratory study was conducted of common clinical conditions as predictors of subsequent cancer in 143,574 outpatients of a health maintenance organization (in California, USA). An association was noted between obesity, diagnosed in 14,388 patients, and the subsequent development of multiple myeloma (MM) in up to 21 years (33 cases observed, 21.3 expected based on the experience of the entire cohort; standardized morbidity ratio = 1.55, 95 percent confidence interval [CI] = 1.06-2.17). This association was evaluated further in a second cohort of 163,561 multiphasic-checkup examinees followed up for as many as 24 years. Body mass index (BMI) at entry examination was associated positively with the incidence of MM in White men (e.g., relative risk [RR] = 1.07, CI = 1.01-1.15 per unit increase in BMI; and RR = 1.68, CI = 0.75-3.78, comparing the highest with lowest quartile). This association was absent in White women, partially confirmed in Black men and women (BMI quartiles two, three, and four showed higher risk than quartile one), and not explained by the presence of diabetes mellitus. The association was reduced or absent with BMI based on reported greatest adult weight, and in White women was inverse with BMI based on reported lowest adult weight. Among subjects with more than one checkup, increased risk was associated directly with weight loss among White men and associated inversely with weight gain among Black women. These findings suggest that body build or nutritional status may be involved in the development of MM by mechanisms that are presently unknown.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7999972 TI - Effect of ethidium binding and superhelix density on the supercoiling free energy and torsion and bending constants of p30 delta DNA. AB - Topoisomer distributions created by the action of topoisomerase I on p30 delta DNA in the presence of various concentrations of ethidium are measured and analyzed using recently developed theory to obtain the twist energy parameter (ET) that governs the free energy of supercoiling in each case. Competitive dialysis experiments to investigate the relative affinity of ethidium for linear and supercoiled DNAs at different binding ratios are assayed fluorometrically and the results are analyzed using related theory. The topoisomer distributions and fluorescence intensity ratios agree well with the theory, which is based on the assumption that the supercoiling free energy varies quadratically with the effective linking difference, regardless of ethidium binding or superhelix density. The topoisomer distribution experiments alone yield an average best-fit value, ET = 950 +/- 80, independent of ethidium binding ratio from r = 0 to 0.082, while the combined topoisomer distribution and ethidium binding experiments yield an average best-fit value, ET = 1030 +/- 90, which is essentially independent of ethidium binding ratio from r = 0 to 0.082 and superhelix density from sigma = 0 to (-)0.053. One may conclude that the supercoiling free-energy-varies quadratically with effective linking difference over the entire range of observed ethidium binding ratios and superhelix densities. The independently measured torsion constant (alpha) of p30 delta DNA is likewise essentially independent of superhelix density and ethidium binding ratio. The observed invariance of ET and alpha implies that the bending constant kappa beta is similarly invariant to superhelix density and ethidium binding ratio. The apparently ideal behavior displayed by p30 delta DNA is not exhibited by pBR322 DNA, which is discussed in the following companion paper. PMID- 7999973 TI - Effect of ethidium binding and superhelix density on the apparent supercoiling free energy and torsion constant of pBR322 DNA. AB - The value of the twist energy parameter (ET) of pBR322 is determined near zero superhelix density from topoisomer distributions created under various conditions. The resulting value, ET = 1155 +/- 65, at 37 degrees C is essentially unaffected by adding 10 mM Mg2+, or by changing the kind of Topo I from chicken red-cell to calf-thymus. This value significantly exceeds that (ET = 950 +/- 80) measured for p30 delta DNA under identical conditions by the same method in the preceding paper. Decreasing the temperature from 37 to 21 degrees C yields a slightly larger value, ET = 1340 +/- 130, but the statistical significance of the increase is marginal. Attempts to determine reliable ET values for pBR322 at higher superhelix densities by ethidium binding were frustrated by the fact that good fits of the equilibrium dialysis results could not be achieved using a single value of ET. Moreover, the curves of apparent ET versus binding ratio r vary considerably from one preparation to another, and for a given preparation vary with time after cell lysis up to about seven weeks, after which they settle in to nearly reproducible behavior. The apparent ET values obtained from competitive dialysis experiments are typically rather low (ET approximately 700) for small r and nearly native superhelix density, and rise up to 1300 to 1500 with increasing binding ratio (up to r = 0.055) and decreasing negative superhelix density.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7999974 TI - A model for the binding of E. coli single-strand binding protein to supercoiled DNA. AB - A model is proposed for the binding of E. coli single strand binding protein (SSB) to supercoiled DNA. The basic tetrameric binding units of SSB are assumed to bind in pairs to the complementary single strands of a locally melted region. The cooperativity of the binding includes contributions from both protein-protein and base-pair stacking interactions. Each bound SSB tetramer is assumed to unwind l = 34 bp, which implies an unwinding angle of 3.27 turns. The resulting loss of superhelical strain is the essential driving force for binding SSB to supercoiled DNAs. All molecular parameters entering into the theory are estimated from available data, except for the composite binding constant (Ka), which is adjusted to best-fit the theory to the fluorescence quenching (FQ) and diffusion coefficient (D0) data of Langowski et al. Very good fits are obtained with optimum values of Ka that are consistent with estimates from other data. This binding model predicts several noteworthy features. (1) SSB binds essentially always in a single contiguous stack on a supercoiled plasmid, and relative fluctuations in stack length are quite small, in agreement with results of electron microscopy studies. (2) The progressive loss of superhelical strain with increasing bound ligand decreases the affinity of the DNA for SSB. This anti cooperativity offsets the cooperativity of the binding and causes apparent saturation of the binding at rather low binding ratios. Consequently, over the limited span of the measurements, the FQ data can also be satisfactorily fitted by a non-cooperative model comprising a small number of independent sites. (3) When SSB binds to a population of different topoisomers, the distribution of linking differences of the resulting complexes is extremely narrow. Thus, SSB acts to level any differences in superhelical strain in a population of topoisomers. Finally, the effects of restricting binding to a region comprising only part of the plasmid are assessed. PMID- 7999975 TI - Reinvestigation of the thermodynamics of spectrin self-association. AB - The thermodynamics of the self-association reactions of human spectrin have been reinvestigated by means of sedimentation equilibrium over the temperature range 18-40 degrees C. The experimental data were analysed in terms of a cooperative isodesmic model of association. The van't Hoff plot showed that the standard change in enthalpy for the heterodimer-tetramer step was temperature-dependent, leading to an estimate of -8.5 kJ mol-1 K-1 for the change in molar heat capacity, delta Cp. Curvature in the van't Hoff plots, not detected in previous studies, was revealed through the increased precision of the data and the wider temperature range examined. On the assumption that delta Cp reflects hydrophobic interactions in the tetramer that cannot be formed in the heterodimer, it can be estimated that approximately 50 CH2 groups per heterodimer participate in hydrophobic interactions in the tetramer that cannot be formed in the heterodimer. PMID- 7999976 TI - Dip patch clamp currents suggest electrodiffusive transport of the polyelectrolyte DNA through lipid bilayers. AB - Planar lipid bilayers formed from monolayers of diphytanoyl lecithin (DPhL) were found to interact with plasmid DNA (5.6 kbp; M(r) = 3.7 x 10(6)) leading to an increase in the conductance of the membrane. The association of DNA with a lipid bilayer greatly facilitates the transport of the small ions of the main salt KCl. The appearance of long-lived current levels, for instance, of 27.6 pA at Vm = +60 mV membrane voltage, where the actual contact (adsorption) is electrophoretically enhanced, suggests a locally conductive DNA/lipid interaction zone where parts of the DNA strand may be transiently inserted in the bilayer, leaving other parts of the DNA probably protruding out from the outer surface of the bilayer. At Vm = 60 mV, where DNA can be electrophoretically moved away from the membrane, the membrane current is practically zero. This current asymmetry is initially also observed at higher voltages, for instance at 200 mV. However, if the voltage sign (Vm = +200 mV) is changed after a transient positive current (approximately 15 pA) was observed, there is also now (at Vm = -200 mV) a finite negative current at the negative membrane voltage. Thus, it appears that at Vm = +200 mV the adsorbed parts of the polyelectrolyte DNA are not only transiently inserted in, but actually also electrophoretically pulled through, the porous zones onto the other membrane side leaving the bilayer structure basically intact. These data provide direct electric evidence for the electrophoretic transport of a highly charged and hydrated macromolecule, probably together with the associated gegen ions, through the thin hydrophobic film of the lipid bilayer. PMID- 7999977 TI - An alternative interpretation of the heat capacity changes associated with protein unfolding. AB - The present study devises a method to get quantitative information for proteins on the theoretically important heat capacity at constant volume. For this purpose expansion coefficients of both the native and unfolded state of a variety of proteins have been determined and used together with compressibility coefficients to calculate the difference between isobaric and isochoric heat capacity, (cp - cv), for the unfolding transition. This difference delta (cp - cv) = (c - c) - (c - c) turns out to be a positive number that is larger than the experimental isobaric heat capacity change (formula:see text) [corrected] for the proteins studied. The generally observed positive heat capacity change on unfolding can therefore alternatively be interpreted as resulting from the difference in work involved in changing the intra- and intermolecular interactions including the weak, highly distance-dependent, van der Waals interactions, for the unfolded and native state, respectively. The difference in expansion work against the atmospheric pressure is negligible. This macroscopic interpretation cannot rule out that part of the denaturational heat capacity increase is also due to the different interaction with water of the native and unfolded conformations of the protein. PMID- 7999978 TI - Genome programmes: an opportunity for biology. AB - The development of human molecular genetics in the eighties led to the implementation of projects aimed at a systematic study of the human genetic make up--the so-called "Genome Projects". These have so far been mainly concerned with genome mapping, both by family studies using polymorphic markers (genetic mapping) and by direct analysis of DNA with suitable fractionation and cloning methods (physical mapping). Major progress has been made in both fields recently. Sequencing per se has remained limited because of technical constraints, although systematic cDNA sequencing has caught on in a large way. National policies are quite diverse, with the USA, the UK, France and Japan being the major players; funding sources range from governments to foundations. Many of the results, methods and concepts obtained or implemented during genome studies can be of great use to "conventional" laboratories, and efficient interfacing between these two worlds is an increasingly important issue. PMID- 7999979 TI - Genes with triplet repeats: a new class of mutations causing neurological diseases. AB - Microsatellites, simple tamdem repeats of 2 to 4 nucleotide sequences, are widely distributed throughout the genome. Trinucleotide repeats are found every 300 to 500 kb. Recently, a new type of mutation was described involving a specific expansion of triplets within or in close proximity to a gene. Expanded triplets have been found in the genes causing six different neurological disorders: fragile X syndrome (FRAXA), spinal and bulbar muscular atrophy (SBMA), myotonic dystrophy (DM), Huntington's disease (HD), spinocerebellar ataxia type 1 (SCA1), and dentato-rubra-pallidoluysian atrophy (DRPLA). These neurological disorders have in common a variable age of onset and clinical severity, as well as a decrease in the age of onset over generations, known as anticipation. These unusual characteristics are related to the observation that expanded repeats are unstable both in meioses and mitoses. A younger age of onset and an increase in severity correlate with a higher number of repeats. Interestingly, particular haplotypes are in disequilibrium with the mutation for FRAXA, DM and HD, suggesting instability for selected chromosomes. How expanded triplets affect the expression and the function of genes is still unknown. Since neurodegenerative disorders are often variable in age of onset and clinical severity, the list of expanding triplet mutations should increase in the very near future. PMID- 7999981 TI - X-linked adrenoleukodystrophy gene: identification of a candidate gene by positional cloning. AB - Adrenoleukodystrophy (ALD) is an X-linked peroxisomal disorder characterized by a progressive demyelination of the central nervous system, adrenal insufficiency and impaired capacity to o-oxidase very long chain fatty acids, a metabolic process that normally takes place in peroxisomes. The ALD locus has been mapped to Xq28 and we have recently identified a patient with ALD who has a complex rearrangement in the 5' end of the red/green color pigment genes in Xq28. This rearrangement comprises two deletions separated by a large inversion. The second deletion of this key ALD patient extends 19 kb into the 3' region of an expressed gene which was found partially deleted in six of 85 independent patients with ALD. This segment thus constitutes a candidate region for the ALD gene. PMID- 7999980 TI - Mitochondrial DNA alterations and genetic diseases: a review. AB - We review the main features of human mitochondrial function and structure, and in particular mitochondrial transcription, translation, and replication cycles. Furthermore, some pecularities such as mitochondria's high polymorphism, the existence of mitochondrial pseudogenes, and the various considerations to take into account when studying mitochondrial diseases will also be mentioned. Mitochondrial syndromes mostly affecting the nervous system have, during the past few years, been associated with mitochondrial DNA (mt DNA) alterations such as deletions, duplications, mutations and depletions. We suggest a possible classification of mitochondrial diseases according to the kind of mt DNA mutations: structural mitochondrial gene mutation as in LHON (Leber's Hereditary Optic Neuropathy) and NARP (Neurogenic muscle weakness, Ataxia and Retinitis Pigmentosa) as well as some cases of Leigh's syndrome; transfer RNA and ribosomal RNA mitochondrial gene mutation as in MELAS (Mitochondrial Encephalomyopathy, Lactic Acidosis and Strokelike Episodes) or MERRF (Myoclonic Epilepsy with Ragged Red Fibers) or deafness with aminoglycoside; structural with transfer RNA mitochondrial gene mutations as observed in large-scale deletions or duplications in Kearns-Sayre syndrome, Pearson's syndrome, diabetes mellitus with deafness, and CPEO (Chronic Progressive External Ophtalmoplegia). Depletions of the mt DNA may also be classified in this category. Even though mutations are generally maternally inherited, most of the deletions are sporadic. However, multiple deletions or depletions may be transmitted in a mendelan trait which suggests that nuclear gene products play a primary role in these processes. The relationship between a mutation and a particular phenotype is far from being fully understood. Gene dosage and energic threshold, which are tissue-specific, appear to be the best indicators. However, the recessive or dominant behavior of both the wild type or the mutated genome appears to play a significant role, which can be verified with in vitro studies. PMID- 7999982 TI - Mapping the Friedreich ataxia locus (FRDA) by linkage disequilibrium analysis with highly polymorphic microsatellites. AB - The Friedreich's ataxia locus (FRDA) is tightly linked to markers D9S5 and D9S15 located in 9q13-q21. Cumulated maximum lod scores between FRDA and D9S5 and between FRDA and D9S15 are above 36 and 61, respectively, at a recombination fraction of 0, indicating that recombination events needed to orient the search of the gene are very difficult to identify and ascertain. We have established a 1 Megabase PFGE map around D9S5 and D9S15 and isolated a corresponding 530 kb YAC contig. We found that the two markers are 260 kb apart. This result was surprising, since D9S5 and D9S15 were independently isolated, but in agreement with the strong linkage between the two loci (lod score > 35 at a recombination fraction of 0). Seven clusters of rare cutter enzyme sites (CpG islands), which are potential indicators of genes, were identified in the 1 Megabase region by PFGE analysis and YAC mapping. The search for genes around the CpG islands is in progress. To map the Friedreich ataxia locus in the absence of clearly identified recombination events, we chose an alternative approach based on haplotype analysis of patients from small populations with precise geographic and historical origins, such as the Louisiana-Acadians, deported from Nova-Scotia about 150 years ago and who remained isolated for historical and cultural reasons. In this population, a single mutation, associated with a specific haplotype may account for the majority of Friedreich ataxia cases. Haplotypes different from the major haplotype at one or the other extremity can indicate ancient recombinations.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7999983 TI - Chromosome rearrangements and human gene mapping. AB - The successful mapping of numerous mendelian disorders by chromosome rearrangements turned out to be a key method for positional location of disease genes. We present some personal observations and comments on the interest of cytogenetic studies in human gene mapping. PMID- 7999984 TI - Cell damage by excess CuZnSOD and Down's syndrome. AB - Down's Syndrome (DS), the phenotypic expression of human trisomy 21, is presumed to result from overexpression of certain genes residing on chromosome 21 at the segment 21q22-the Down locus. The "housekeeping" enzyme CuZn-superoxide dismutase (CuZnSOD) is encoded by a gene from that region and its activity is elevated in DS patients. Moreover, the recent discovery that familial ALS is associated with mutations in the gene encoding CuZnSOD, focused attention on the entanglement of oxygen-free radicals in cell death and neuronal disorders. To investigate the involvement of CuZnSOD gene dosage in the etiology of the syndrome we have developed both cellular and animal models which enabled us to investigate the physiological consequences resulting from overexpression of the CuZnSOD gene. Rat PC12 cells expressing elevated levels of transfected human CuZnSOD gene were generated. These transformants (designated PC12-hSOD) closely resembled the parental cells in their morphology, growth rate, and response to nerve growth factor, but showed impaired neurotransmitter uptake. The lesion was localized to the chromaffin granule transport mechanism. These results show that elevation of CuZnSOD activity interferes with the transport of biogenic amines into chromaffin granules. Since neurotransmitter uptake plays an important role in many processes of the central nervous system, CuZnSOD gene-dosage may contribute to the neurobiological abnormalities of Down's Syndrome. As an approach to the development of an animal model for Down's Syndrome, several strains of transgenic mice which carry the human CuZnSOD gene have been prepared. These animals express the transgene as an active enzyme with increased activity from 1.6 to 6.0-fold in the brains of four transgenic strains and to an equal or lesser extent in several other tissues. To investigate the contribution of CuZnSOD gene dosage in the neuropathological symptoms of Down's Syndrome, we analyzed the tongue muscle of the transgenic-CuZnSOD mice. The tongue neuromuscular junctions (NMJ) in the transgenic animals exhibited significant pathological changes; withdrawal and destruction of some terminal axons and the development of multiple small terminals. The ratio of terminal axon area to postsynaptic membranes decreased, and secondary folds were often complex and hyperplastic. The morphological changes in the transgenic NMJ were similar to those previously seen in the transgenic NMJ and were similar to those previously seen in muscles of aging mice and rats as well as in tongue muscles of patients with Down's Syndrome. The findings suggest that CuZnSOD gene dosage is involved in the pathological abnormalities of tongue NMJ observed in Down's Syndrome patients.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 7999985 TI - Isolation and characterization of the gene responsible for the X chromosome linked Kallmann syndrome. AB - Kallmann de Morsier Syndrome is defined by the association of an hypogonadism with an anosmia. The hypogonadism is due to a deficiency of GnRH (gonadotropin releasing hormone). Olfactory bulbs and tracts are underdeveloped in the patients. Embryological studies have indicated that the migration of GnRH neurons and the axonal extension of olfactory neurons, which both originate in the olfactory epithelium during embryogenesis, were impaired in a fetus affected by X linked Kallmann Syndrome. By a positional cloning strategy, we have isolated the KAL gene, responsible for the X-linked form of the disease. The gene consists of 14 exons. A highly homologous pseudogene on the Y chromosome has been characterized. The KAL gene encodes a putative secreted protein of 680 amino acids, which contains four fibronectin type III repeats and a four disulphide core motif. The former motif is usually associated with adhesion function. The latter has been described in protein with antiprotease activity. We have isolated the chicken KAL homologue and studied its expression by in situ hybridization during late embryonic development. The gene is expressed in various neuronal populations of the central nervous system, including mitral cells of the olfactory bulbs. We suggested that the KAL protein might be involved in late neuronal differentiation. PMID- 7999986 TI - Mapping of the Down syndrome phenotype on chromosome 21 at the molecular level. AB - Phenotypic and molecular analysis of individuals with partial trisomy 21 can be used to determine which regions of chromosome 21 are involved in the pathogenesis of specific features of Down's Syndrome. Using dosage analysis of 27 sequences we defined, at the molecular level, the extent of the chromosome 21 duplication in ten individuals with partial trisomy 21. Phenotype-genotype correlations led to the definition of minimal regions, the duplications of which are linked to the expression of 23 clinical features of Down's Syndrome. The D21S55 region or Down's Syndrome Chromosome Region 1 (DCR1) (1/20 of the long arm), on 21q22.2 21q22.3 proximal, is involved in four cardinal features of the disease: mental retardation, growth retardation, muscular hypotonia and joint hyperlaxity, and in eight of the 18 more common morphological anomalies of the face, hands and feet. Overlapping the DCR1, the D21S55-MX1 region or DCR2 (1/10 of the long arm), spanning 21q21.2 down to the 1/4th proximal part of 21q22.3, is involved in the features defined by the DCR1 plus congenital heart defect and five additional morphological anomalies. Thus, our results indicate that duplication of a relatively small region of chromosome 21 plays a critical role in the pathogenesis of the Down's phenotype. PMID- 7999987 TI - Mutations and impaired expression in the ACHE and BCHE genes: neurological implications. AB - The acetylcholine hydrolysing cholinesterases control the termination of cholinergic signalling in multiple tissues and are targets for a variety of drugs, natural and man-made poisons and common insecticides. Molecular cloning and gene mapping studies revealed the primary structure of human acetyl- and butyrylcholinesterase and localized the corresponding ACHE and BCHE genes to the chromosomal positions 3q26-ter and 7q22, respectively. Several different point mutations in the coding region of BCHE were found to be particularly abundant in the Israeli population. Analytical expression studies in microinjected Xenopus oocytes have demonstrated that the biochemical properties of cholinesterases may be modified by rationalized site-directed mutagenesis and in chimeric ACHE/BCHE constructs. These properties are differently altered in the various allelic BCHE variants, conferring resistance to several anti-cholinesterases, which may explain the evolutionary emergence of these multiple alleles. At the clinical level, abnormal expression of both ACHE and BCHE and the in vivo amplification of the ACHE and BCHE genes has been variously associated with abnormal megakaryocytopoiesis, leukemias and brain and ovarian tumors. Moreover, antisense oligonucleotides blocking the expression of these genes were shown to interfere with hemocytopoiesis in culture, implicating these genes in cholinergic influence on cell growth and proliferation. PMID- 7999988 TI - The effect of different collagens and of proteoglycan on the retraction of collagen lattice. AB - The effect of various collagens and proteoglycan on the formation and retraction of collagen lattices was tested. The most rapid aggregation of collagen molecules was observed by the use of the least cross-linked collagen fractions (ie pepsin digested calf skin collagen type I). Lattices formed with more cross-linked collagens (acid soluble collagen-ASC, type III) contracted slowly and less intensively. Unpurified pepsinized cartilage extract containing collagen types II, IX and XI, some glycoproteins and proteoglycans formed lattices rather well. On the contrary, purified collagen type II as well as polymeric collagen (solubilized by denaturing conditions) did not form lattices at all. The lattice formation and retraction was intensified by addition of proteoglycan into the culture medium. The authors suggest that the kinetics of the lattice formation and retraction depends on the amount of collagen cross-links and the concentration of proteoglycan in the culture medium. PMID- 7999989 TI - Effect of purified IgGs from HIV-1-infected and non infected individuals on immune activation. AB - The purification and analysis of IgGs from sera of HIV-1-infected and non infected individuals are reported. The effect of antibodies purified from sera of infected individuals on antigen-induced T cell proliferation was investigated in relation to their possible involvement in an autoimmune reaction in AIDS, in view of the previously unravelled striking peptide similarities between HIV-1 gp120 and the immunoregulatory CD4 and Fas molecules. However, our data do not allow definite conclusions to be drawn. The necessity of purifying antibodies against specific peptides to show their direct effect on T-cell activation is further stressed. PMID- 7999990 TI - Unexpectedly higher expression levels of a chimeric 2S albumin seed protein transgene from a tandem array construct. AB - In wild-type Arabidopsis seeds the 2S albumin seed protein gene family members are differentially expressed. In this work it is shown that as predicted by the wild type situation, the at2S2 promoter is much more effective than that of the at2S1 gene in the expression of a transgene. However, unexpectedly high expression levels were obtained using a construct in which the transgene was present as a tandem duplication in the T-DNA. Neither in this case nor in homozygous plants with either construct was epigenetic silencing observed. While transgene mRNA levels were of the same order of magnitude as the endogenous at2S2 gene, protein levels were much lower. PMID- 7999991 TI - Non-systemic expression of a stress-responsive maize polyubiquitin gene (Ubi-1) in transgenic rice plants. AB - We have used the promoter, 1st exon and 1st intron of the maize polyubiquitin gene (Ubi-1) for rice transformation experiments and revealed the characteristic expression of Ubi-1 gene: (1) Ubi-1 gene is not regulated systemically but rather individual cells respond independently to the heat or physical stress; (2) Ubi-1 gene changes its tissue-specific expression in response to stress treatment; (3) the expression of Ubi-1 gene is dependent on cell cycle. PMID- 7999992 TI - Characterisation of the cDNA clones of two beta-tubulin genes and their expression in the potato plant (Solanum tuberosum L.). AB - The cDNA clones of two potato beta-tubulin genes were isolated from a tuberising stolon tip library. Analysis of 20 positive clones showed that they represented one or another of two different but very similar beta-tubulin genes, designated TUBST1 and TUBST2. The expression pattern of beta-tubulin genes in the potato plant was investigated by RNA blot analysis and by RT-PCR. Southern analysis of potato genomic DNA with coding and non-coding beta-tubulin probes revealed that there are multiple beta-tubulin genes in the potato genome and that there is likely to be considerable divergence in the 3' non-coding sequences. Phylogenetic analysis of plant beta-tubulin genes is described. PMID- 7999993 TI - Molecular cloning and characterization of a legumin-like storage protein cDNA of Douglas fir seeds. PMID- 7999994 TI - Reduced ethylene synthesis by transgenic tomatoes expressing S-adenosylmethionine hydrolase. AB - We have utilized a gene from bacteriophage T3 that encodes the enzyme S adenosylmethionine hydrolase (SAMase) to generate transgenic tomato plants that produce fruit with a reduced capacity to synthesize ethylene. S adenosylmethionine (SAM) is the metabolic precursor of 1-aminocyclopropane-1 carboxylic acid, the proximal precursor to ethylene. SAMase catalyzes the conversion of SAM to methylthioadenosine and homoserine. To restrict the presence of SAMase to ripening fruit, the promoter from the tomato E8 gene was used to regulate SAMase gene expression. Transgenic tomato plants containing the 1.1 kb E8 promoter bore fruit that expressed SAMase during the breaker and orange stage of fruit ripening and stopped expression after the fruit fully ripened. Plants containing the 2.3 kb E8 promoter expressed SAMase at higher levels during the post-breaker phases of fruit ripening and had a substantially reduced capacity to synthesize ethylene. PMID- 7999995 TI - Molecular cloning and biochemical characterization of a receptor-like serine/threonine kinase from rice. AB - A receptor-like protein kinase, OsPK10, has been cloned from rice (Oryza sativa). The 2.8 kb cDNA contains an open reading frame capable of encoding a peptide sequence of 824 amino acids. The topological features of the predicted OsPK10 protein include an N-terminal signal peptide, a cysteine-rich extracellular ligand-binding domain, a membrane-spanning segment, and a cytoplasmic domain possessing all the hallmarks of catalytic domains of eukaryotic protein kinases. The cytoplasmic domain was selectively expressed in Escherichia coli and assayed for kinase activity. The results show the protein is capable of autophosphorylation using either ATP or GTP as the phosphate donor. Phosphoamino acid analysis reveals phosphorylation of threonines, consistent with the substrate specificity indicated by sequence motifs in the catalytic core. A single amino acid substitution of Glu for Lys-528 completely abolishes autophosphorylation activity. DNA gel blot analyses suggest that the haploid rice genome contains a single copy of the OsPK10 gene. OsPK10 transcripts appear to be more abundant in shoots than in roots of rice seedlings. PMID- 7999996 TI - A dehydrin cognate protein from pea (Pisum sativum L.) with an atypical pattern of expression. AB - Dehydrins are a family of proteins characterised by conserved amino acid motifs, and induced in plants by dehydration or treatment with ABA. An antiserum was raised against a synthetic oligopeptide based on the most highly conserved dehydrin amino acid motif, the lysine-rich (core sequence KIKEK-LPG). This antiserum detected a novel M(r) 40,000 polypeptide and enabled isolation of a corresponding cDNA clone, pPsB61 (B61). The deduced amino acid sequence contained two lysine-rich blocks, however the remainder of the sequenced differed markedly from other pea dehydrins. Surprisingly, the sequence contained a stretch of serine residues, a characteristic common to dehydrins from many plant species but which is missing in pea dehydrin. The expression patterns of B61 mRNA and polypeptide were distinctively different from those of the pea dehydrins during seed development, germination and in young seedlings exposed to dehydration stress or treated with ABA. In particular, dehydration stress led to slightly reduced levels of B61 RNA, and ABA application to young seedlings had no marked effect on its abundance. The M(r) 40,000 polypeptide is thus related to pea dehydrin by the presence of the most highly conserved amino acid sequence motifs, but lacks the characteristic expression pattern of dehydrin. By analogy with heat shock cognate proteins we refer to this protein as a dehydrin cognate. PMID- 7999997 TI - Genomic organization of the canrep repetitive DNA in Brassica juncea. AB - Canrep is a heterogeneous, tandemly repeated, 176 bp nucleotide sequence that contains a single Hind III site and is present in high copy numbers in the genomes of many Brassica species. Complete clusters of repeats of this DNA were cloned from the nuclear DNA of Brassica juncea. Restriction-fragment dimers and higher multimers of the 176 bp sequence have arisen by mutations within the Hind III recognition sequence. Adjacent repeats from within the same cluster usually have different nucleotide sequences with features indicating that diversity is generated by a mechanism that causes site-specific base substitutions. While most of the units of canrep DNA are clustered in long arrays of tandem repeats, some are dispersed throughout the genome as isolated copies or in small clusters. Regardless of the size of the arrays, each cluster begins and ends with a variable-length, truncated repeat and is flanked by inverted copies of the sequence 5'-ATCTCAT3'-, which is not part of the basic sequence of the canrep family of DNAs. Furthermore, some clusters are located close to nucleotide sequences related to those of known plant transposons. Thus, canrep elements may be dispersed by transposition. There are two distinct subfamilies of canrep sequences in B. juncea, and one of these is closely related to one of the two subfamilies of this type of DNA from B. napus, indicating that it originated from B. campestris, the common diploid ancestor of both amphidiploid species. Neither the repetitive DNA nor nucleotide sequences flanking canrep clusters are transcribed in seedlings, suggesting that even small arrays of repeats are located in heterochromatic regions and might be involved in chromatin condensation and/or chromosome segregation. PMID- 7999999 TI - Identification and expression of the chloroplast clpP gene in the conifer Pinus contorta. AB - The clpP gene from the conifer Pinus contorta was identified and isolated from a chloroplast genomic library by heterologous hybridisation to the second exon of the chloroplast clpP gene in tobacco. DNA sequencing of two overlapping clones revealed an uninterrupted 615 bp open-reading frame with 41 to 65% similarity to the clpP genes in five other chloroplast genomes and Escherichia coli. The 615 bp sequence in P. contorta contained perfectly matched motifs for the serine and histidine active sites of the ClpP protease in E. coli. The location of the clpP gene was determined using a physical map of the P. contorta chloroplast genome, and was found to lie within a 10 kb region between the psbE/F and rpoB genes. Sequencing of the regions adjacent to the clpP gene revealed the first exon of the rps12 gene located 135 bp downstream. The genomic position of the first exon of the rps12 gene in relation to the clpP gene is conserved for all other chloroplast clpP genes identified so far. Northern blot analysis showed that the clpP gene in both P. contorta and P. sylvestris was present in several transcript of different length, ranging from 0.8 to 2.4 kb. The two longer transcripts in P. contorta also included the first exon of the rps12 gene. Mapping of the 5' end of the clpP transcripts by primer extension, however, revealed a single transcription initiation site 53 bp upstream of the first ATG codon. Analysis of total RNA isolated from the two pine species grown in darkness or moderate light conditions (250 mumol photons m-2 s-1) showed no significance difference in the level of expression of the clpP gene. The results suggest that the clpP gene in conifers is part of an operon which includes the first exon of the rps12 and the entire rpl20 gene, and is expressed in a light-independent manner as a polycistronic precursor which later undergoes post-transcriptional processing to give the mature monocistronic clpP mRNA. PMID- 7999998 TI - Environmental stress-mediated differential 3' end formation of chloroplast RNA binding protein transcripts. AB - We report the characterization of transcripts from the halophyte, Mesembryanthemum crystallinum, encoding a protein with high homology to chloroplast RNA-binding proteins (cRBP). In this plant chloroplast-related functions are largely protected against salt stress. cRBP transcripts are derived from a single gene, Mc32crbp, although three size classes of polyadenylated mRNAs are detected. Transcription rate and steady state amounts of mRNA are developmentally regulated and light controlled with strong transcriptional activity as functional chloroplasts are established, and with lower maintenance activity thereafter. Upon salt stress, the rate of transcription decreases, although transcript levels increase. Accompanying stress, a change in the distribution of transcript size classes is observed as the longest transcript with an untranslated 3' end of 381 nucleotides increases relative to transcripts with shorter 3' ends. The long transcript is characterized by the presence of five sequence elements in the 3'-untranslated region that are present in cRBP mRNAs from a variety of plants, although not all elements are found in each mRNA. The results may indicate a mechanism by which mRNA levels of constitutively light regulated genes may be modulated without enhanced transcription in response to environmental cues. PMID- 8000000 TI - Porphobilinogen deaminase is encoded by a single gene in Arabidopsis thaliana and is targeted to the chloroplasts. AB - Porphobilinogen deaminase (PBG deaminase) is an early enzyme of the pathway for chlorophyll and heme synthesis. Using degenerate oligonucleotide primers, based on amino acid sequence data for purified PBG deaminase from pea, a fragment was amplified from Arabidopsis genomic DNA by PCR, and then used to isolate both a cDNA and a genomic clone for PBG deaminase from Arabidopsis. The cDNA, shown to be full-length by primer extension, encodes a precursor protein of 382 residues, which can be imported into isolated chloroplasts and processed to the mature size. The genomic clone encodes an identical sequence to the cDNA, except for the presence of four introns within the coding region of the mature protein, and 1.7 kb of upstream sequence. There is no obvious TATA box within 50 bp of the transcription start. Southern blot analysis suggests that PBG deaminase is encoded by a single gene in the Arabidopsis genome, and RNase protection experiments demonstrated that this gene is expressed in both leaves and roots. These results support the conclusion that there is only one form of PBG deaminase in all plant cells, which is located in the plastid. PMID- 8000002 TI - Organization and characterization of Cucurbita phloem lectin genes. AB - The phloem of pumpkin and squash contains a dimeric chitin-binding lectin called PP2 (phloem protein 2). We have isolated three genomic clones from pumpkin (Cucurbita maxima Duch.) that encoded PP2. One clone, lambda gPC13-1, contained two PP2 genes that were 99.8% identical over a region of 3055 nucleotides. This conserved region included 1922 bp of 5' non-coding sequence, 844 bp of protein coding sequence (including two introns), and 289 bp of 3' non-coding sequence. To examine the conservation of the phloem lectin within the genus Cucurbita, we analyzed nine different species for PP2, its mRNA, and the genes that encode PP2. DNA blot analysis indicated that each species contained genes that encoded PP2, however, there was considerable restriction fragment length polymorphism (RFLP) among the species. PP2 gene copy number reconstructions indicated that PP2 is encoded by a small gene family (two to eight genes). Although a high level of PP2 DNA polymorphism existed among species, a single mRNA (ca. 1 kb) was detected in each species. PP2, affinity-purified from the vascular exudate of each species, reacted with PP2-specific antibodies; five species contained a single PP2 polypeptide while four species contained two PP2 polypeptides. PMID- 8000001 TI - Identification of potential regulatory elements in the far-upstream region of the Arabidopsis thaliana plastocyanin promoter. AB - The far-upstream region of the Arabidopsis thaliana plastocyanin (Pc) promoter acts positively on transcription. This -1580 to -710 region (relative to the translation start site) has enhancer-like properties since it is also functional when situated downstream of the gene. Using tobacco nuclear extracts, this region was tested for protein-binding sites. Two short binding sequences were identified. The AT-rich sequence separating these binding sites shows extensive homology to the sequences separating the paired GT-1-binding sites of the pea rbcS-3A promoter. The requirements for complex formation strongly suggest that a GT-1-like protein binds to the two identified boxes in the Pc promoter. Sequence comparisons revealed that both boxes fit within the moderate consensus sequence needed for GT-1-binding. This GT-1-like DNA-binding activity is present in light grown as well as in dark-adapted plants. Therefore, the possible role for GT-1 in light regulation of transcription does not depend upon its de novo synthesis. In some of the gel mobility shift assays, an additional DNA-protein complex was formed. The formation of this complex was only observed if the heteropolymer poly(dAdT).poly(dAdT) was used as a non-specific competitor and was dependent on the CpG density of the probe used. PMID- 8000003 TI - Molecular changes of organelle DNA sequences in rice through dedifferentiation, long-term culture, or the morphogenesis process. AB - Callus-specific rearranged DNA in rice (Oryza sativa L.) was isolated by in-gel reassociation procedure. Southern hybridization experiments revealed that some clones were amplified significantly in primary callus induced from scutellum tissue. Rapid amplification of these clones was observed within 2 days after plating seeds onto callus-induction medium containing 2,4-D. NAA gave no significant effect on DNA amplification event. Colony formation process from isolated protoplasts and plant regeneration process from callus showed clone specific and process-specific fluctuation patterns of copy number. Sequence analysis of the clones suggested that most of the clones were originated from organelle DNA. Comparison of copy number fluctuation pattern of organelle functional genes with that of the clones suggested multiformity and/or construction-specific amplification of organelle DNA. PMID- 8000004 TI - Avenacosidase from oat: purification, sequence analysis and biochemical characterization of a new member of the BGA family of beta-glucosidases. AB - A protein consisting of 60 kDa subunits (As-P60) was isolated from etiolated oat seedlings (Avena sativa L.) and characterized as avenacosidase, a beta glucosidase that belongs to a preformed defence system of oat against fungal infection. The enzyme is highly aggregated; it consists of 300-350 kDa aggregates and multimers thereof. Dissociation by freezing/thawing leads to complete loss of enzyme activity. The specificity of the enzyme was investigated with para nitrophenyl derivatives which serve as substrates, in decreasing order beta fucoside, beta-glucoside, beta-galactoside, beta-xyloside. The corresponding orthonitrophenyl glycosides are less well accepted. No hydrolysis was found with alpha-glycosides and beta-thioglucoside. An anti-As-P60 antiserum was prepared and used for isolation of a cDNA clone coding for As-P60. A presequence of 55 amino acid residues was deduced from comparison of the cDNA sequence with the N terminal sequence determined by Edman degradation of the mature protein. The presequence has the characteristics of a stroma-directing signal peptide; localization of As-P60 in plastids of oat seedlings was confirmed by western blotting. The amino acid sequence revealed significant homology (> 39% sequence identity) to beta-glucosidases that are constituents of a defence mechanism in dicotyledonous plants. 34% sequence identity was even found with mammalian and bacterial beta-glucosidases of the BGA family. Avenacosidase extends the occurrence of this family of beta-glucosidases to monocotyledonous plants. PMID- 8000005 TI - Termini and telomeres in T-DNA transformation. AB - A T-DNA vector for plant transformation has been constructed in which the cloning site is located 9 bp from the right-border (RB) end and 27 bp from the left border (LB) end. In this vector cloned DNA homologous to plant chromosomal sequences is located at the T-DNA termini, and will thus be exposed by even limited exonucleolysis in planta. The arabidopsis ADH (alcohol dehydrogenase) locus was mobilized from Agrobacterium, and integration into the recipient genome was studied. Despite the terminal location of ADH homology in this vector, the T DNA integrated essentially at random in the Arabidopsis genome rather than at the endogenous ADH locus. T-DNA integration was blocked, however, when Arabidopsis telomeric sequences were added to the construct at each end of the ADH homology. Thus the predominant mode by which incoming T-DNA is integrated into the continuity of chromosomal DNA involves free DNA ends, but, in contrast to modes of recombination such as gap repair, does not involve extensive terminal DNA sequence homology. PMID- 8000006 TI - Organ-specific reduction in the abundance of a mitochondrial protein accompanies fertility restoration in cytoplasmic male-sterile radish. AB - The mitochondrial DNA of plants containing the male sterility-causing Ogura cytoplasm of radish contain a novel gene, orf138, that is transcribed as part of a bicistronic mRNA. Genetic studies have previously linked male sterility with the orf138 locus. To determine if orf138 is expressed at the protein level, and investigate the effect of fertility restoration on ORF138 levels, we have raised antibodies to an ORF138-glutathione S-transferase fusion protein. Anti-ORF138 antibodies detect a 20 kDa protein that is associated with the mitochondrial membrane of sterile Ogura radish plants. Nuclear restoration is accompanied by a dramatic reduction in the amount of this protein in mitochondria of flowers and leaves, but not roots of fertile Ogura radish plants. The presence or absence of fertility restoration genes has no detectable effect on the size, abundance, or RNA editing patterns of orf138 transcripts. These results support genetic studies that have implicated orf138 in Ogura cytoplasmic male sterility and suggest that the restorer genes may be affecting either the translation or stability of ORF138. PMID- 8000007 TI - Domain conservation in several volvocalean cell wall proteins. AB - Based on our previous work demonstrating that (SerPro)x epitopes are common to extensin-like cell wall proteins in Chlamydomonas' reinhardtii, we looked for similar proteins in the distantly related species C. eugametos. Using a polyclonal antiserum against a (SerPro)10 oligopeptide, we found distinct sets of stage-specific polypeptides immunoprecipitated from in vitro translations of C. eugametos RNA. Screening of a C. eugametos cDNA expression library with the antiserum led to the isolation of a cDNA (WP6) encoding a (SerPro)x-rich multidomain wall protein. Analysis of a similarly selected cDNA (VSP-3) from a C. reinhardtii cDNA expression library revealed that it also coded for a (SerPro)x rich multidomain wall protein. The C-terminal rod domains of VSP-3 and WP6 are highly homologous, while the N-terminal domains are dissimilar; however, the N terminal domain of VSP-3 is homologous to the globular domain of a cell wall protein from Volvox carteri. Exon shuffling might be responsible for this example of domain conservation over 350 million years of volvocalean cell wall protein evolution. PMID- 8000008 TI - Detection of immunologically related Kunitz and Bowman-Birk proteinase inhibitors expressed during potato tuber development. AB - Antiserum against a potato Kunitz-type proteinase inhibitor (PKPI) expressed in Escherichia coli was produced. In immunoblotting assays of proteins from potato tubers cultured in vitro, three proteins reacted to the antiserum, two of 20 kDa and one of 10 kDa. Their N-termini were sequenced. While the 20 kDa proteins showed 59 and 90% identity to PKPI, the 10 kDa one had 65% identity to soybean C II proteinase inhibitor. Characterization of the temporal expression of these proteins showed that both could be detected from 10 days after induction of tuberization (DAI) in vitro, but the times when maximum amounts of PKPI and 10 kDa protein could be detected were different, corresponding to 22 and 32 DAI, respectively. The amounts of these proteins decreased in the following stages, and no positive reaction of the antiserum with mature tuber proteins could be found. The 20 kDa proteins were also detected in early stages of development of potato tubers grown in the field, indicating that these proteins are expressed during normal tuber development, and differ from the PKPIs reported previously. PMID- 8000009 TI - A corolla- and carpel-abundant, non-specific lipid transfer protein gene is expressed in the epidermis and parenchyma of Gerbera hybrida var. Regina (Compositae). AB - We are examining the floral organ differentiation in Compositae by isolating and characterizing corolla abundant genes. Differential screening of a cDNA library made from the ray floret corolla of Gerbera hybrida var. Regina revealed an abundant cDNA clone which is expressed in the corolla but not in leaves. This cDNA (gltp1) codes for a polypeptide similar to non-specific lipid transfer proteins of the plants. The gltp1 gene is expressed only in the corolla and carpels and is developmentally regulated during corolla development. The gltp1 mRNA accumulates both in epidermal cell layers and in the mesophyll of the corolla. In the stylar part of the carpel, the gltp1 mRNA can be detected in the epidermal and in parenchymal cells but not in the transmitting tissue. Analogous patterns of gltp1 expression in the corolla and carpel may indicate that similar genetic programmes operates during the development of these two tissues. PMID- 8000010 TI - Isolation and characterization of P-type H(+)-ATPase genes from potato. AB - H(+)-ATPase cDNAs were identified in a potato leaf library using an Arabidopsis gene as a probe. Based on their sequences, the clones could be grouped into at least two classes. A similar classification was obtained from the analysis of sequence data from four tobacco genes. Both potato genes are expressed in all tissues analysed, higher levels of expression were found in leaves and stem than in roots and tubers. For both genes, no significant differences in level of expression could be detected under a variety of conditions such as cold treatment, anaerobiosis, sucrose induction or treatment with a synthetic cytokinin. Only 2,4-D and prolonged periods of darkness lead to a slight reduction in mRNA levels. The reduction in darkness was compensated after transfer of the plants back into the light. Expression of the ATPase genes remained constant in transgenic plants which are inhibited in phloem loading due to antisense inhibition of the sucrose transporter. On the other hand, expression of the sucrose transporter is inducible by auxin and cytokinin but not by sucrose. Taken together, these data suggest that at least the two plasma membrane H(+)-ATPase genes analysed are rather constant in their expression and that either other genes respond to external stimuli or that most of the regulation occurs at the posttranscriptional level. PMID- 8000011 TI - Cloning and expression of the soybean DapA gene encoding dihydrodipicolinate synthase. AB - The rate-limiting step in the pathway for lysine synthesis in plants is catalyzed by the enzyme dihydrodipicolinate synthase (DS). We have cloned the portion of the soybean (Glycine max cv. Century) DapA cDNA that encodes the mature DS protein. Expression of the cloned soybean cDNA, as a lacZ fusion protein was selected in a dapA- Escherichia coli auxotroph. The DS activity of the fusion protein was characterized in E. coli extracts. The DS activity of the fusion protein was inhibited by lysine concentrations that also inhibited native soybean DS, while E. coli DS activity was much less sensitive to inhibition by lysine. PMID- 8000012 TI - Nucleotide sequence analysis of a cDNA clone encoding the 34K movement protein gene of odontoglossum ringspot virus, ORSV-Cy, the Korean isolate. AB - The partial nucleotide sequence of the 3'-terminal region of the Korean isolate of odontoglossum ringspot tobamovirus (ORSV-Cy) from cool-growing Cymbidium was determined. The sequence contained a full length open reading frame (ORF) coding for the viral cell-to-cell movement protein (MP). The ORF was located upstream of the coat protein gene and 105 nucleotides longer than that of tobacco mosaic virus (TMV). The ORF predicts a polypeptide chain of 303 amino acids with a molecular weight of 33573. The ORF contained a similar region of conserved sequence motif of tobamoviruses and putative assembly origin of the viral RNA was located at about 1,100 nucleotides away from the 3' end. The predicted amino acid sequence for the MP gene of ORSV-Cy is more closely related to pepper mild mottle virus (PMMV), TMV-vulgare and TMV-Rakkyo than to tobacco mild green mosaic virus (TMGMV), TMV-L, cowpea strain of TMV (SHMV), and cucumber green mottle mosaic virus (CGMMV). PMID- 8000014 TI - The classification and taxonomy of hepatitis viruses. PMID- 8000013 TI - [Advances in gastrointestinal peptides: gastrin]. AB - Classical hormones (present in blood circulation), neuro-endocrine agents (released in the neural synapses), paracrine substances (disseminated around neighbouring cells) and autocrine factors (acting upon its own generating cell) constitute the universe of gastrointestinal peptides. Early gastrointestinal endocrinology has progressed into the current "receptorology" age. Technological advances have naturally produced an almost alluvial amount of information. This review addresses to several features of gastrin, a member of the gastrin/cholecystokinin family: a) participation in the regulation of gastric acid secretion; b) secretory cells receptors; c) hypergastrinemia and its influence upon enterochromaffin-like cells in characteristic clinical situations; d) histamine release regulation; and e) gastrin receptors and their potential actions on normal and neoplastic colonic epithelium. PMID- 8000015 TI - [The serological response to a recombinant DNA vaccine in the native residents of 2 hyperendemic hepatitis B areas in the Peruvian Amazonia]. AB - In large areas of the Amazon jungle from Brazil, Colombia, Venezuela and Peru, it has been reported hyperendemic HBV and delta focus. In the Peruvian jungle we found up to 97% of prevalence of HBV, on the northern Jivaro tribes vs the southern tribes, Arawak, (65%). In this paper we studied 226 volunteers from 6 Jivaro and 3 Arawak villages, who accepted to be vaccinated with a DNA recombinant vaccine (ENGERIX B); all of them were previously HBsAg/Ab negatives but 55.5% of them were anti-core (IgG) positive. Our results show 84.9% of seroconversion to anti-HBs, and 73.5% was consider to be immunized (> 10 mIU/ml). Better response was observed in those that were HBcAb negative, coming from a low endemic area. We also observed a good vaccine response although we had to change months the response decreased up to 51.8% of seroimmunity. Higher anti-HBs titles was observed in the southern tribes: MGC of 416.3 mIU/ml. compared with the south: MGC: 182.2 mIU/ml. CONCLUSIONS: It is important to check previously, in hyperendemic areas, HBV markers, specially. It is important to receive the second dose between with the third dose up to 14 month. The immune response overall was good: the ABsAb titles obtained was in average, 290 mIU/ml (10.2-41,00). Apparently the vaccine do not suffer during the difficulties in transportation in the jungle. No side effects we shown during the vaccination program. PMID- 8000016 TI - [Pneumatic dilatation in patients with esophageal achalasia]. AB - From October 1984 to March 1992, 21 patients of Hospital Nacional Guillermo Almenara Irigoyen-IPSS, Lima, Peru, with esophageal achalasia were treated with pneumatic dilatation using a 3.5 cm diameter Rider-Moeller balloon. The mean age was 40.5 years (range: 24-54). Six were men and 15 women. The mean time with dysphagia previous to treatment was 5.3 years. A total of 29 sessions were performed, 1.38 sessions per patient. The follow-up of the first 10 patients was carried for a mean time of 48.3 months (range:6-91). A satisfactory response to treatment was obtained in 8 patients (80%). Two patients (20%) relapsed after 2 and 3 treatment sessions needing surgery. One patient suffered a esophageal perforation recovering after surgical treatment. We conclude that pneumatic dilatation with Rider-Moeller balloon is a safe and not difficult medical procedure for esophagus achalasia. PMID- 8000017 TI - [Abdominal tuberculosis in childhood: the clinical manifestations]. AB - The authors reviewed the histories of 133 patients with abdominal tuberculosis in Instituto Nacional de Salud del Nino (Children's Hospital), Lima, Peru, between 1989 and 1991. We found morbidity higher in scholars (67.4%). Weight lost were present in all cases and malaise in 95.3%, abdominal distension in 83.72% and abdominal pain in 79.06%. Anaemia in 76.06%, ratio albumin/globulin were altered in 74.41% leukocytosis in 67.44%. Evidence of tuberculosis on chest X-ray were detected only in 62.5%. PMID- 8000018 TI - [An index of the severity of intestinal gangrene due to colonic volvulus]. AB - This retrospective analysis evaluated 50 patients with gangrenous colonic volvulus two cases with ileocecal volvulus, one case with volvulus of the colon transverse and 47 cases with sigmoid volvulus- who were managed by primary resection with anastomosis (n = 21) or resection plus colostomy (n = 29) at Belen Hospital, Trujillo, Peru, from January 1, 1967 to July 31, 1993. The principal aim of the study was to identify by univariate analysis the combination of predictive risk factors for postoperative mortality. The following factors were associated with increased mortality: mean arterial pressure lower than 70 mmHg (p = 0.004), presence of purulent or fecaloid peritoneal fluid (p = 0.013) or evidence of macroscopic bowel perforation (p < 0.001). A method of quantifying the risk of mortality following gangrene of the loop using these factors was described. Each factor was given a weight value ranging from 0 a 2 (0 = major, 1 = moderate, 2 = minor) according to the severity of injury estimate. The sum of the individual factor scores comprised the final score of the Severity of Gangrenous Colon by Volvulus (S.S.G.C.). In this series the 30-day mortality rate was of 30%. A S.S.G.C. resulted greater than 4 in 34 (68%) of the patients. This was associated with a 9% mortality rate and contrasted to a 75% when the S.S.G.C. was equal to or less than 4. Mortality developed in 33% of the patients operated on using an immediate anastomosis (S.S.G.C., 4.2 +/- 0.99) and it was of 28% in those whose operation was resection plus colostomy (S.S.G.C., 3 +/- 0.87).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8000019 TI - [The program of the Publications of the Pan American Health Organization (PAHO) organized in Caracas a Workshop of the Editors of Biomedical and Health Journals of the Andean Region]. PMID- 8000020 TI - [Therapeutic colonoscopy in patients with colonic and rectal polyps]. AB - 598 colorectal polyps were removed by therapeutic colonoscopy from 377 patients, of both sexes, between 1 and 88 years old, most of them with lower digestive symptoms. The polyps were unique in 67.37% and multiple in 32.63% of patients, and mostly located in rectum and sigmoid colon; 42.14% were pedunculated, 33.95% sessile++/sub-pedunculated, and 23.91% sessile in shape. In 51% the size was over 10 mm in diameter. Histologically, 68.68% were of epithelial neoplastic type: 60.91% adenoma; 6.42% adenoma with adenocarcinoma, and 1.35% polypoid carcinoma. 30.64 were epithelial non-neoplastic type: 20.32% hyperplastic polyp, and 0.51% hyperplastic polyp with tubular adenoma. Two patients (0.53%) had lower digestive hemorrhage immediately after the polypectomy. The complications were controlled with conservative measures without blood transfusion. PMID- 8000022 TI - [The current situation and treatment strategy for gastric cancer at the National Cancer Center of Tokyo, Japan]. AB - At the National Cancer Center of Tokyo Gastric Division, from 13/09/1993 to 12/11/93, 42 gastrectomies, 3 local resections and 1 exploratory laparotomy, for gastric cancer, were carried out. Resection R2 were carried out in 29/42 (69%), resection R2 plus dissection of the station 16 in 5/42 (12%), resection R3 plus dissection of the station 16 in 4/42 (9.5%) and distal pancreas preserving in 11/14 (78.6%) of the total gastrectomies. The most frequently type of reconstruction done after distal gastrectomy was Billroth 1 in 20/28 (71.4%) and the most frequent stage of the disease was la-b in 34/46 (74%). Postoperative severe complications were present in 5/42 (12%) and the most frequently histological type was tubular adenocarcinoma 27/46 (58.7%). PMID- 8000021 TI - [Megaloblastic anemia associated with chronic diarrhea. A prospective and multicenter study in Lima]. AB - Since 1986 we have been observing an increased number of patients with megaloblastic anaemia (MA) associated to chronic diarrhea. In 60% of the cases we could not identify any etiologic factor. In the last three years a prospective study in Lima (Peru) has been carried on aimed to investigate this aspect; patients with diseases recognized to be associated to MA were excluded. 45 patients were included age average 37.5 years, all of them have a confirmed diagnosis by bone marrow; 64% with low serum B12 and folic acid, 20% with low serum B12, and 16% with low serum folic acid. Gastric biopsies did not show atrophy in 67%; intragastric pH was lower than 4 in 50% duodenal content culture was positive in 35% (6/17) to aerobic gram negative agents; 62% (5/8) of duodenal biopsies, 83% (5/6) of jejunal biopsies, 4/4 (100%) of ileal biopsies, showed diverse structural changes; 100% did not show Diphyllobothrium pacificum. All these findings make us suggest that a significative number of patients with MA and chronic diarrhea in Lima are related to small bowel bacterial overgrowth. These bacteria can "sequestrate" or consume folates and cobalamines besides the direct damage they can cause to intestinal morphology. Future studies are needed to confirm our proposal and define if these cases belong to a variety of tropical sprue. PMID- 8000023 TI - [Pediatric colonoscopic polypectomy]. AB - Colorectal polyps are relatively frequent in infancy and constitute one of the main causes of bleeding per rectum. Endoscopic polypectomy, with its lower morbidity and mortality, has revolutionized its treatment. Between October 1, 1985 and May 31, 1994, 122 polypectomies were done in 88 pediatric patients. Forty five patients (51.1%) were male and 43 female (48.9%). Forty four patients (50%) were between 1 and 5 years of age. Ninety five polyps (77.9%) were found more frequently in the rectum. Regarding the size, 63 polyps (51.6%) measured between 1 and 2 cm. Seventy three patients (83%) had a single polyp, 10 patients (11.4%) had 2 polyps and 1 patient had 12 polyps. Ninety six polyps (78.7%) were pedunculated, being this the more frequent form found. Histologically the most common was the juvenile polyp, found in 106 cases (87.6%). The polypectomies was carried out without using general anesthesia and is performed as an outpatient procedure. We had no experience of endoscopic complications. It is concluded that colonoscopy polypectomy is a useful, simple and safe procedure for treating colorectal polyps in children. PMID- 8000024 TI - [Acute intermittent porphyria at the Hospital Arzobispo Loayza of Lima (1983 1994). A report of 14 cases]. AB - In order to determine the incidence and clinical characteristics of acute intermittent porphyria (AIP) a retrospective study was done in Hospital Arzobispo Loayza of Lima for the period 1983-1994. Of 16 patients with that diagnosis, 14 ones (13 female and one male) entered to the study because of their clinical pictures and a positive Watson Schwartz' test. All were Hispanics from Lima. The average age was 24 yr old. The average for delay of diagnosis was 7 days and for hospitalization was 24 days. There was 1.8 AIP attacks by patient. Only 3 patients (21.4%) had familial history of AIP. The most frequent exacerbating factors were infections (52%), menses (20%) and drugs (16%). The main findings were:abdominal pain (100%), hyporexia (100%), nausea and vomit (84%) and dark urine (80%); hyporeflexia (52%); tachycardia (100%), fever (44%), arterial hypertension (40%) and abdominal distention (40%); anemia (52%), hyponatremia (48%), elevated ESR (40%) and increased activity of SGOT and SGPT (36%). It was found an annual incidence of 1.05 AIP cases and 1.9 attacks by 1000 discharged patients from the Medicine wards. Besides, we found similar clinical characteristics in our patients as it has been reported in the medical literature. PMID- 8000025 TI - [The prevalence of giardiasis in patients who undergo gastroduodenoscopy]. AB - Giardiasis constitutes a very frequent intestinal parasitic infection in our country, with a varied digestive symptomatology. We performed a prospective, transversal study, with the aim to establish the frequency of G. lamblia in digestive symptomatic patients submitted to upper gastrointestinal endoscopy examination trying to relate its isolation with the endoscopic findings. We studied 50 patients; they were submitted to upper endoscopy examination. During the procedure, we aspirated duodenal content and six duodenal biopsies were taken; 8 to 14 hours before endoscopy, they swallowed the Enterotest encapsulated string. The presence of G. lamblia was established by three methods (Enterotest, duodenal content, impront). The day, of the endoscopic examination they resolved a questionnaire of digestive symptoms they had during the last 4 weeks. The endoscopy was informed like normal in 15 patients. (30%). Duodenitis was detected by endoscopy in 9 patients (18%), but neither one of them demonstrated presence of G. lamblia. By the three diagnostic methods, the presence of G. lamblia was demonstrated in 5 patients (19%), without endoscopic duodenitis, being the digestive symptom scores not statistically significant respect to symptomatic patients without G. lamblia. We concluded that the three diagnostic methods used to identify G. lamblia were equally sensitive. No preponderance of digestive symptoms were present in patients with G. lamblia in relation to in our country patients without G. lamblia infection. We recommend to consider duodenal aspiration during endoscopy in order to discard giardiasis. PMID- 8000026 TI - [Advances in gastrointestinal hormones: cholecystokinin]. AB - Cholecystokinin (CCK) and gastrin are members of an important family of gastroenteropancreatic polypeptides. Distribution of CCK both in the digestive system and central and peripheral nervous structures correlates with the variety of its actions; more than a classic hormone, CCK is a peptidergic neurotransmitter. CCK plays a predominant role in multiple digestive functions: contraction and emptying of the gallbladder, stimulation of pancreatic secretion of enzymes, delay of gastric emptying, diminution of gastric acid secretion, regulation of insulin secretion, reduction of food intake, etc. Distinction between pharmacologic and physiologic effects has been difficult in all of these areas. Modern technological procedures have generated significant progresses: reliable plasmatic bioassay, understanding of molecular heterogeneity, identification and characterization of receptors and their subtypes, agonists and antagonists, some of them currently available for research studies. The integrationist perspective of normal and pathological physiology has been considerably enhanced. Therapeutic use of CCK and its derivatives in some specific problems, i.e. obesity and anorexia, remains incipient and restricted. PMID- 8000027 TI - [Tubercular liver abscess: a case report and discussion of the literature]. AB - A case of an isolated tuberculous abscess of the liver in a 47-years-old woman with a 2-year history of disease is presented. Only 17 similar cases have been reported previously in the literature. The symptomatology of this patient, confused initially with a chronic calculous cholecystitis and then with an hepatic pyogenic abscess exemplify what has been described for this rare disease presentation. A review of the pertinent literature is presented. PMID- 8000028 TI - Introduction: commitment to CD4 and CD8 lineages--stochastic or instructive? PMID- 8000029 TI - The effect of constitutive CD8 expression on thymic selection; implications for the mechanism of CD4 and CD8 lineage commitment. AB - The choice of an immature T cell to become a CD4 cell or a CD8 cell may be the result of instructive signals generated during positive selection. Alternatively, the initial commitment to a CD4 or CD8 lineage may be made independently of the specificity of the TCR. In this article, I describe our efforts to test the latter possibility using mice expressing a constitutive CD8 transgene. If lineage commitment is initially independent of MHC specificity, expression of ectopic CD8 in CD4 cells should allow CD4 cells with class I specific TCR to mature. We find that although some mature class I specific CD4 cells can be detected in CD8 transgenic mice, they are a minor population compared to class I selected CD8 cells. The implications of these results for the mechanism of lineage commitment are discussed. PMID- 8000030 TI - Do the CD4 and CD8 lineages represent parallel pathways? AB - It is now well established that the progression of T cell development requires interactions between the surfaces of thymocytes and thymic stromal cells. For example, the maturation of CD4+8+ cells into functional CD4+ or CD8+ cells requires TCR/MHC interactions, which, depending on the specificity of the particular TCR, direct the thymocyte to the appropriate lineage. Beyond this, little is known about the molecular mechanism of this lineage choice. Here we describe our recent studies of CD4/CD8 lineage commitment using TCR transgenic mice expressing a well-defined MHC class II specific TCR. While the results of these experiments are inconsistent with a model in which CD4 versus CD8 lineage is determined by an initial TCR/MHC/co-receptor interaction, they also do not support a simple stochastic model of lineage commitment. Instead, we suggest that the CD4 and CD8 lineage may not represent equivalent pathways of T cell maturation. Additionally, we draw several parallels between stochastic models in positive selection and in hematopoiesis. PMID- 8000031 TI - CD4 and CD8 in T cell lineage commitment: alterations induced by expression of a CD8/CD4 chimeric transgene. AB - The mechanism by which thymocytes expressing both the CD4 and CD8-coreceptor proteins differentiate into mature T cells expressing either CD4 or CD8 is not well understood. We have shown that expression of a chimeric CD8/CD4 transgene can alter T cell lineage commitment such that cells expressing a transgenic class I major histocompatibility complex-restricted T cell receptor can differentiate to the CD4 rather than those the CD8 lineage. The implications of these findings and those of others for existing instructive and stochastic models of thymocyte lineage commitment are discussed, and an alternative model is considered. PMID- 8000032 TI - The different roles of MHC class recognition in thymocyte CD4 versus CD8 lineage commitment and positive selection. AB - Commitment to the CD4+ or CD8+ T cell lineages and positive selection for full maturation of precursor T cells take place in the thymus. A detailed phenotypic analysis of differentiating thymocytes in normal and MHC-deficient mice has led to the identification of previously unappreciated subpopulations whose characteristics and dependence on major histocompatibility complex (MHC) class I versus class II molecule expression seem incompatible with a CD4/CD8 coreceptor dependent 'instructional' model of thymocyte development. We suggest here that these and other recent data are most consistent with a model in which the TCR mediated decision to enter the CD4 versus the CD8 lineage is independent of the class of MHC molecule recognized and is distinct from positive selection. This latter event appears to involve already lineage-committed cells and to require a match of the MHC class specificity of the lineage-defining, highly expressed CD4 or CD8 coreceptor and the TCR. PMID- 8000033 TI - In favor of the selective model of positive selection. AB - The mechanisms of thymocyte commitment towards the CD4+ and CD8+ lineage remain unresolved. Two models--one based on instruction, the other on selection--have previously been proposed. The instructional model has been popularly received based on results of earlier studies. However, our data from MHC class II, class I, and double-deficient mice suggest otherwise. There exists a significant population of CD4+ cells that is intermediate in maturity between CD4+ CD8+ and fully mature CD4+ CD8- thymocytes in class II-deficient animals; an analogous population of CD4-CD8+ cells exists in class I-negative mice. We suggest that a selective model in which two TCR-MHC molecule engagements are required: the first induces a random down-modulation of either CD4 or CD8 and some differentiation; the second, involving the participation of the appropriate coreceptor, permits end-stage differentiation. PMID- 8000034 TI - CD4/CD8 lineage commitment in T cell receptor transgenic mice: evidence for precommitment of CD4+ CD8+ thymocytes. AB - CD4+ and CD8+ mature T cells arise from CD4+ CD8+ thymic precursors by a process of positive selection that ultimately requires interaction of the T cell receptor (TCR) with self major histocompatibility complex (MHC) molecules. The mechanism of commitment of immature CD4+ CD8+ thymocytes to CD4 or CD8 lineages is controversial. Using TCR transgenic mice, we present evidence that CD4+ CD8+ thymocytes are precommitted to either the CD4 or CD8 lineage, prior to positive selection and independently of TCR specificity for MHC. This lineage precommitment model places important constraints on signaling via CD4 or CD8 coreceptor molecules. PMID- 8000035 TI - [XVIIth Congress of the Society of Biomechanics. Toulouse, 17-18 September 1992. Abstracts]. PMID- 8000036 TI - Effects of an ingested glutamate arginine salt on ammonemia during and after long lasting cycling. AB - The purpose of this study was to examine the effect of glutamate-arginine salt (AGs) or placebo (P1) on ammonemia during and after 1 hour exercise on sporting event bicycle under ergonomic device at 80% VO2max in 3 healthy male volunteers (age 18-25 years). Subjects were tested in three sessions, at rest after AGs and during exercise with placebo (Pl) or AGs. The subjects were given 20 g of AGs or Pl orally and 30 min later, exercised at 75-80% VO2max for 30 min. Blood samples were taken at 0, +30, +60, +90, +120 min after AGs and analyzed for ammonemia. Our results show a highly significant increase in plasma ammonia concentration during exercise. The magnitude of this increase was diminished when subjects were given AGs before the exercise session, suggesting that AGs may help reduce physiologic fatigue. PMID- 8000037 TI - Experimental conditions affecting in vitro intestinal incorporation of palmitic acid: a methodological approach. AB - In the rat, a large number of in vitro studies on intestinal fatty acid uptake have been carried out. However, the results obtained under different experimental conditions are often contradictory. The present work is a critical approach to the experimental aspects which may modify in vitro intestinal uptake of fatty acids. Different kinds of intestinal tissue samples (intact, everted or opened rings) were used. The histological changes and the uptake of palmitic acid were measured for each type of sample under different stirring rates, at different incubation times and with micellar solutions of varying composition. It is concluded that 1) opened rings have the highest absorptive capacity with the lowest dispersion; 2) incubation periods longer than 30 minutes do not result in additional palmitic acid uptake and may lead to severe tissue hypoxia as indicated by extensive vacuolization; 3) stirring rates over 1 cycle/sec do not result in increased PA uptake and cause extensive mucosal disruption, particularly in jejunal samples. PMID- 8000038 TI - Effect of dopamine on ecto-5'-nucleotidase expression in human glomerular mesangial cells. AB - Ecto-5'-nucleotidase (5'-ribonucleotide phosphohydrolase, EC 3.1.3.5) of mesangial cells may be the main source of adenosine within the glomerulus, and thus essential in the regulation of glomerular microcirculation. c-AMP and c-AMP stimulating agents were found to induce ecto-5'-nucleotidase of mesangial cells. Dopamine is a catecholamine known to increase c-AMP levels in mesangial cells. We have studied the effect of dopamine on ecto-5'-nucleotidase expression and DNA synthesis of glomerular mesangial cells in culture. Human mesangial cells were exposed to dopamine in the concentration range from 0.1 microM- to 1 mM, for 6-72 h. Ecto-5'-nucleotidase activity of human mesangial cells increased from 118.6 +/ 7.7 to 171 +/- 12 nmol/min/mg in a 72 h culture. This effect was time- and dose dependent. Cycloheximide, an inhibitor of protein synthesis did not modify basal 5'-nucleotidase activity but it suppressed the stimulatory effect of 10 microM dopamine. DNA synthesis of human mesangial cells, studied after exposure of these cells to the same concentrations of dopamine used in the 5'-nucleotidase stimulation, was inhibited, being also dose dependent. These results indicate that dopamine induces ecto-5'-nucleotidase and inhibits DNA synthesis of cultured human mesangial cells. This action of dopamine on glomerular mesangial cells may be important in the regulation of glomerular hemodynamics. PMID- 8000039 TI - Homogentisic acid and structurally related compounds as intermediates in plasma soluble melanin formation and in tissue toxicities. AB - Homogentisic acid (HGA) spontaneously starts to undergo oxidation and polymerization soon after the beginning of incubation in human blood or plasma at 37 degrees C, and forms plasma soluble melanins (PSM). Haemolysis accompanies this process in blood. The addition of equimolar quantities of antioxidants delays this oxidation significantly (isoascorbic acid by 2:30-4:00 h; glutathione by 3:20-4:05 h; D-penicillamine by 5:00-5:45 h). HGA is a phenylalanine and tyrosine metabolite, related structurally to the catecholamines and other precursors of melanins. HGA is normally metabolized by the enzyme homogentisic acid oxidase. When this enzyme is genetically missing, part of HGA is excreted in the urine, another part polymerizes darkens many tissues (ochronosis), and produces widespread degenerative changes in cartilage and other connective tissues, joints, blood vessels, heart valves, kidneys and in other tissues. Collectively this disorder is known as alcaptonuria, for which no satisfactory treatment is known. The causes of both alcaptonuric arthritis and rheumatoid arthritis are thought to involve increased oxidative stress. Inflammation of joints and connective tissue damage are involved in both diseases. Oxygen radicals are suspected to cause inflammation and cellular damage. Hydroxyl radicals degrade hyaluronic acid (the viscous synovial fluid of joints). High levels of products of free radical reactions, with fluorescence excitation (ex) and emission (em) maxima in the wavelength ranges of those of PSM (ex 320-400 and em 400-470) were reported in the blood sera and synovial fluids of patients with rheumatoid arthritis.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8000040 TI - Phenytoin treatment and folate supplementation affect concentrations of folates in tissues of cobalamin-deficient rats. AB - To further define the mechanism of interaction among phenytoin, folates and cobalamins in rats, we studied the effect of phenytoin (60 mg/(kg.day)) with or without folic acid supplementation and with or without cobalamin deficiency, as well as the effect of supplementing with folic acid (200 mg/kg diet) with or without a cobalamin deficiency, on the tissue concentrations of folates and phenytoin (determined respectively by HPLC and fluorescence polarization). The major tissues (liver, intestinal mucosae, blood and brain) were studied. A folic acid overload (estimated at about 2 mg/day) increased folate levels in the liver, the intestinal mucosae and blood, while there was no effect on cerebral levels. Phenytoin had no significant effect on folate tissue concentration. The major finding was that a folic acid overload caused a considerable decrease in the hepatic and cerebral concentrations of phenytoin. This decrease could be responsible for the increased frequency of epileptic fits in patients treated with this anticonvulsant drug when combined with a folic acid supplement. Concentration changes of the drug in cobalamin-replete or -deficient rats, with or without folic acid supplementation, suggest that the interaction between the anticonvulsant and the two vitamins (folates and cobalamins) occurs at the level of transmethylation reactions. PMID- 8000041 TI - Effect of adrenergic receptor blockade on plasma testosterone response to exercise in conscious dogs. AB - The aim of this study was 1) to establish the relationship between testosterone (T) levels and the intensity and duration of exercise in conscious dogs, and 2) to investigate the involvement of the sympathetic system in the response of plasma T to acute exercise. The experiments were performed on 14 male mongrel dogs (20-25 kg) trained to run on a motor driven treadmill. Testosterone (T), cortisol, epinephrine, norepinephrine, lactate and haematocrit were measured in arterial blood samples. A brief intensive exercise (leading to exhaustion within 5 or 20 min) induced a marked increase in plasma T, while during more prolonged (60 min) exercise plasma T showed an initial increase followed by a secondary decrease. Blockade of the beta adrenergic receptors with propranolol (Inderal 0.5 mg/kg i.v.) did not modify the changes of plasma T during exercise, but blockade of alpha adrenergic receptors with phentolamine (Regitine 0.5 mg/kg) lowered the exercise induced rise in plasma T. PMID- 8000042 TI - [Bilateral carotid occlusion in the rat neonatally treated with capsaicin]. AB - Bilateral carotid occlusion (BCO) was performed in pentobarbital anesthetized adult rats neonatally treated with capsaicin (50 mg/kg, sc, CNT rats). Pressor and ventilatory responses to BCO in CNT rats were compared with those of littermate controls injected with a same volume of solvent (olive oil, 0.1 ml). Capsaicin was used in order to produce partial degeneration of unmyelinated C fibres related to baroreflexes and peripheral chemoreflexes. In control rats, BCO provoked in less than 5 s, hyperventilation, hypocapnia and hyperoxia. Systemic arterial hypertension and tachycardia developed more slowly. They were maximum at 65 s. At this time, ventilation was returned to control values. Hyperventilation results from the stimulation of the carotid chemoreceptors by stagnant asphyxia generated by the blood flow stop. Hypertension and tachycardia are provoked by an increase in the orthosympathetic outflow when carotid baroreceptors are unloaded. In a first time, chemoreceptors stimulation tends to oppose to the increase of heart rate in normal rats. In a second one, development of hypertension is autolimited by the stimulation of the aortic baroreceptors particularly effective in rats. Simultaneously the hyperoxic inhibition from aortic chemoreceptors, the central hypocapnia and the reperfusion of the carotid bodies lead to the suppression of hyperventilation. As hyperventilation decreases when hypertension develops, even in rats with vago-sympathetic section at low cervical level, the part of aortic baroreceptors effects is probably reduced except for the fibres travelling through superior laryngeal nerves. Carotid bodies reperfusion seems to predominate. Before any manipulations, CNT rats had lower heart rate and systemic blood pressure than controls. During BCO, initial hyperventilation was moderately prolonged as hypertension slowly developed.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8000043 TI - N-tert-butyl-alpha-phenylnitrone administration fails to modify alcohol dependence and alcohol induced hypervascularization. AB - Chronic alcoholization by ethyl-alcohol inhalation was used to study the properties of a spin-trapping agent on different alcohol manifestations in rat. The spin-trapping agent, i.e. N-tert-butyl-alpha-phenylnitrone (PBN), was given at the dose of 32 mg/kg twice a day during the whole alcoholization procedure. The blood alcohol level, the hypermotility which accompanied the ethanol withdrawal, the behavioral dependence as estimated by a free-choice program and the hypervascularization which is developed after a chronic pulmonary alcoholization were quantified. The rats treated with PBN differ from the control rats only by their higher blood alcohol level at the end of the chronic alcoholization while the other quantified alcohol-induced manifestations remained unchanged. PMID- 8000044 TI - Changes in the renin-angiotensin-aldosterone system in 2 kidney -2 clip Goldblatt hypertensive rats of both sexes submitted to chronic hypobaric hypoxia. AB - The effect of chronic hypobaric hypoxia (CHH) on the development of 2k-2c Goldblatt renovascular hypertension has been analyzed in rats of both sexes. Results have shown lower values of blood pressure (BP) in all the animals exposed to CHH compared with their normoxic control (P < 0.001). Haematocrit was increased by adaptation to CHH (P < 0.001), and was larger in male than in female hypoxic rats, both normotensive (P < 0.05) and hypertensive (P < 0.01). Plasma renin activity was higher in normoxic and hypoxic hypertensive female rats than in their normotensive controls (P < 0.05). Plasma angiotensinogen concentration was higher in normoxic control male rats than in all the other groups. This difference disappeared after adaptation to CHH or development of hypertension. Plasma aldosterone concentration was lowest in normoxic control male rats and the difference also disappeared after CHH or renal ischemia. Present data indicate that CHH blunts the hypertensive response to bilateral renal ischemia in male and female rats. Sexual differences related to the mechanisms that could be involved in hypertension development have been observed. The renin-angiotensin-aldosterone system might be modulated by gonadal hormones during the development of hypertension. PMID- 8000045 TI - Time to exhaustion at VO2max and lactate steady state velocity in sub elite long distance runners. AB - The aim of the present study was to estimate the importance of lactate steady state velocity (WCL) of the running velocity at maximal oxygen uptake (Va max) and its time to exhaustion (Tlim), in the performance of a half marathon stated by the velocity over 21.1 km sustained by the runners during 1 h 12 min +/- 2 min 27 s. The population consisting of ten sub-elite male long distance runners (32 +/- 4 years old) was homogeneous with regard to their velocities on 21 km (V21 = 17.5 +/- 0.88 km.h-1, coefficient of variation, CV = 5%) and their aerobic maximal speed (Va max) (21.6 +/- 1.2 km.h-1, CV 6%). The fractional utilization of VO2max on 21 km was calculated from their own running economy (oxygen consumed per kilo of body mass and kilometer run (194 +/- 74 ml.kg-1.km-1). V21 represented 83 +/- 5% VO2max (VO2max = 68.1 +/- 4.1 ml.kg-1.min-1) and 81 +/- 3.3% Va max. The velocity corresponding to lactate steady state and called "lactate steady state velocity" (WCL) was measured according to a protocol proposed by CHASSAIN (1986). The subjects ran twenty minutes at a constant velocity representing 70-75% and 85-90% VO2max. Lactatemia was measured at the fifth (Lact 5) and the twentieth minute (Lact 20). Lactate slope was measured for two running velocities in order to determine the velocity (WCL) corresponding to lactate steady state, i.e. the lactate slope is equal to zero.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8000046 TI - Day time and night time effects of 24R,25-dihydroxycholecalciferol on renal alkaline phosphatase and gamma-glutamyltransferase activities in intact rats. AB - The effects of 24R,25-dihydroxycholecalciferol [24,25(OH)2 CC] on alkaline phosphatase (APA), gamma-glutamyltransferase (gamma-GT) and acid phosphatase (AP) activities were investigated on renal cortex slices of intact rats killed at 18h00 or at 06h00. At 06h00, three, six and nine hours after a single intraperitoneal injection of 24,25(OH)2 CC, APA activity was increased by 30%, 51% and 29%, respectively and gamma-GT activity, by 25%, 39% and 38%, as compared to their controls. AP on the other hand was not modified at all. These enzymatic stimulations were statistically higher than those measured at 18h00, respectively APA: 11%, 25%, 28% and gamma-GT: 2%, 20%, 22%. They can be explained by variations in new protein synthesis in relation with rat activity periods. Physiological significance of these renal effects remains to be elaborated. PMID- 8000047 TI - Spectral frequency analysis of dynamic balance in healthy and injured athletes. AB - Different neurophysiological circuits underlie the various frequencies of the body sway for the regulation of human upright posture. Servo-controlled platforms allowed experimental studies about latency responses after a sudden external disturbance but power frequency repartition during spontaneous dynamic equilibrium has rarely been examined. The purpose of the present study was to examine the zone of sway frequency assigned to proprioceptive afferences from muscular, articular and tendinous receptors in healthy and injured subjects standing on an unstable and minimal area. Dynamic balance conditions were realized by asking athletes to stand up on a seesaw (stabilometer). The recordings (stabilograms) were monitored by means of an accelerometer. Their power spectra were obtained by a fast Fourier transform process. A first study was conducted in order to specify the contribution of articular receptors of the ankle in the regulation of spontaneous dynamic equilibrium of five soccer players with unilateral injured ankle (IA). The balance parameters in lateral sways were measured in monopodal stance on the healthy ankle (HA) comparatively to IA. The stabilogram was longer (P < 0.05), the total energy of 2-20 Hz band (P < 0.01) higher in the IA (1074 +/- 111 mm and 53 +/- 8 V2) than in the HA (836 +/- 150 mm and 36 +/- 8 V2). A second study analyzed the contribution of knee articular receptors involved in the reflexes of antigravity extension. We assessed during bipodal stance the anteroposterior sways of five basketball players with injured knee (IK) and 3 with healthy knee (HK) in eyes-open and eyes-closed situations.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8000048 TI - Effects of oleic and elaidic acids on in vitro intestinal uptake of cholesterol in the rat. AB - The effects of oleic and elaidic acid upon the in vitro intestinal uptake of cholesterol were studied in 9 weeks-old male and female rats. Elaidic acid increases the uptake of cholesterol when compared to oleic acid in both males and females. It is suggested that elaidic acid may enhance the esterification of cholesterol within the enterocyte through being more available for esterification and/or through being preferentially incorporated into cholesterol esters. PMID- 8000049 TI - Effects of temperature on in vitro palmitic acid uptake by chicken and rat intestinal tissue. AB - The intestinal absorption of fatty acids proceeds by simple or facilitated diffusion, a mechanism which is affected by temperature. However, most studies in this field have not taken into consideration the fact that birds have higher physiological temperature than mammals, the absorption being studied at 37 degrees C in both cases. The aim of this work has been to find out whether the higher palmitic acid (PA) uptake rate in birds (chickens) compared to mammals (rats) is attributable to the differences between their body temperatures (41.5 degrees C for chickens and 37.5 degrees C for rats). PA-uptake was studied in intestinal (ileal and jejunal) tissue samples of both Hybro broiler chickens (male and female, 4 weeks-old) and Ico:OFA rats (males and females, 8 weeks-old). The intestinal tissue samples were incubated in micellar solution (0.6 mM 14C-PA; 0.3 mM monoolein; 3.4 mM sodium taurodeoxycholate) at 37.5 degrees C and 41.5 degrees C in both cases. Chicken intestinal tissue incorporated PA with higher efficiency at 41.5 degrees C than at 37.5 degrees C. In contrast, increasing the incubation temperature to 41.5 degrees C led to a decrease in PA uptake by female rat intestinal tissue whereas specimens from male rats exhibited the same absorptive efficiency. These results suggest that the incubation temperature determines to some extent the efficiency of fatty acid uptake. However the fact that the temperature caused opposite effects in rats and chickens indicates that the changes in temperature affect the intracellular processing of the fatty acids already taken up rather than the diffusion of fatty acids through the enterocyte brush-border membrane. PMID- 8000050 TI - [Autoregulation of body weight and body composition in man. A systematic approach through models and simulation]. AB - The regulation of body weight and its composition in humans is examined from the standpoint of system analysis. It is based upon the hypothesis that the ultimate purpose for modulating body energy stores is to ensure the maximum duration for survival of the individual in the face of calorie deficit. A mathematical model, which is built on this hypothesis, allows quantitative simulation of variations in body weight and composition which occur during cycles of underfeeding/refeeding, and is achieved with the use of three global parameters. One of them controls the partitioning of body energy stores between fat and lean tissues, and the other two are concerned with the control of adaptive thermogenesis. The first of these two parameters for thermogenesis modulates the efficiency of fat storage by a function which is inversely proportional to the level of replenishment of the adipose tissues, and the other one controls regulatory thermogenesis which is a direct function of energy imbalance. These two forms of adaptive thermogenesis operate independently of each other and their amplitude depends upon the nutritional background of the individual. This model can be used as a theoretical framework for integrating numerous data in the literature on physiological processes that are involved in the regulation of body weight and body composition. PMID- 8000051 TI - [Role of NO in cardiovascular and respiratory physiology]. AB - Nitric oxide (NO) is now considered as the endogenous nitrovasodilator which is mainly derived from vascular endothelial cells in physiological conditions. Biosynthesis of NO is controlled by a family of enzymes, the NO synthases (NOS), that can be divided into two major subgroups, namely the constitutive and the inducible NOS. The constitutive NOS is the principal isoform found in endothelial cells. Endothelial dysfunction, as seen in chronic hypoxic lung diseases, impairs endogenous production of NO, thereby causing and/or aggravating pulmonary hypertension. A logical means to reduce pulmonary hypertension would consist in supplying the patients with exogenous NO. Given by inhalation, NO is a selective pulmonary vasodilator, as it rapidly combines with haemoglobin, which inactivates NO, and therefore prevents the occurrence of systemic hypotension. Endothelial dysfunction resulting in reduced NO synthesis is also likely to account for various cardiovascular disorders, including essential hypertension and coronary atherosclerosis. However, the importance of endogenous NO in the modulation of bronchial tone remains to be established. Current investigations include studies looking at regulatory mechanisms of cellular expression of various NOS isoforms on the one hand and, on the other hand, clinical evaluation of short- and long term inhalation of NO in patients with primary and secondary pulmonary hypertension. PMID- 8000052 TI - [Implication of neuroexcitatory amino acids in the anatomo- functional organization of the central gray nucleus: physio-pathological aspects]. PMID- 8000053 TI - [Otoacoustic emissions in the human]. AB - Otoacoustic emissions are sounds emitted by the cochlea, basically deriving from the active micromechanical properties of the outer hair cells of the organ of Corti. As they can be recorded painlessly and non-intrusively, they provide a good means of studying human cochlear functioning. In this report, the main types of otoacoustic emission are described, with their characteristics and relation to cochlear functioning. The contribution of otoacoustic emission studies to the physiology of the medial olivocochlear system is discussed, this being the only sensitive and non-intrusive way of studying this system, the function of which remains uncertain. PMID- 8000054 TI - Mouse antibody response following repetitive injections of gamma-irradiated human placenta collagen. AB - Injectable bovine collagen has been used clinically for years. But both the necessity of repeated injections to maintain corrections and the question of adverse allergic reactions developing from the use of a xenogenic collagen have been an area of serious concern. To overcome these adverse effects, we have developed injectable collagen preparations from human placenta. Gamma irradiation was used for sterilization and crosslinking of the collagen. We observed the mouse immune response to gamma-irradiated human placenta soluble and insoluble collagen following multiple injections. After six injections of these materials, no total IgG level increase was found, nor was antibody specifically directed against human collagen found. Mouse antibody levels were also observed following Zyderm II and Zyplast repetitive injections and following repetitive implantations of coated vicryl and chromic gut. No humoral immune response was found in this heterologous type system. PMID- 8000055 TI - Characteristics of two-dimensional and color Doppler ultrasonography in Graves' disease. AB - Color Doppler flow imaging (CDFI) was performed in 24 patients with Graves' disease and the results were compared with those from 8 patients with Hashimoto's disease, 6 patients with simple diffuse goiter, and 15 normal volunteers. All cases were confirmed by clinical, laboratory tests or pathology. CDFI of Graves' disease showed diffuse or localized hypoechoes within the thyroid glands, rich flow signals in the hypoechoes, accelerated flow velocity, and decreased resistance in the superior thyroid arteries (STA) and arteries within the glands. These appearances were characteristic as compared with the controls. The rate of flow in STA of Graves' disease patients was 8 to 10 times higher than that in the normal volunteers. This study demonstrates that CDFI is convenient and efficient as compared with isotope scan and some other laboratory tests, and can be widely used in the diagnosis of Graves' disease. PMID- 8000056 TI - Expression of HLA-class II genes of IDDM patients on the surface of the LTK- cells. AB - To investigate the function of HLA-class II genes in the autoimmune response of insulin dependent diabetes mellitus (IDDM), the HLA-class II gene of IDDM patients was introduced into Ltk- cells with pSV2-neo plasmid, using the calcium phosphate precipitation technique. We obtained a stable cell line expressing the HLA-class II gene from lymphocytes of IDDM patients. Expression was identified by direct ox erythrocyte-CrCl3-HLA DR monoclonal antibody rosetting. PMID- 8000057 TI - Antispermatogenic effect of Tripterygium wilfordii and tripchlorolide (T4) on rat gametogenesis and spermatozoa. AB - The multiglycosides of Tripterygium wilfordii (TII), a ready-made Chinese herbal medicine used for the treatment of rheumatoid arthritis, have been shown to cause oligospermia in patients. In the present study, the antifertility effects of TII and tripchlorolide (T4, isolated from TII) were observed in male rats. In rats fed with TII at a dose of 10 mg.kg.d for 7 weeks, the seminiferous tubules were essentially not influenced. However, most of the sperm heads along the surface of the tubular lumen were transformed from the normal sickle-shaped to round shaped, suggesting a possible mutagenic action. There was minimal testicular change but prominent epididymal spermatozoa damage in all rats treated with T4 (0.05 mg.kg.d) for 7 weeks. The epididymal spermatozoa showed various structural abnormalities, including disrupted connecting pieces and cracked midpieces, and more than 80% of the spermatozoa were decapitated. No significant changes were seen in the main visceral organs. The data suggest that T4 may have good prospects as a male contraceptive. PMID- 8000058 TI - A case-control epidemiologic study of endometriosis. AB - A case-control study involving 203 cases of pelvic endometriosis seen from 1987 1989, and 406 randomly selected and age-matched community controls was conducted in order to provide information relevant to effective prophylaxis of the disease. The diagnosis was confirmed by pathology from laparotomy and/or laparoscopy. A questionnaire focused on menstrual, marital and reproductive status, professional exposure and physical activities, and the results were analyzed by a conditional logistic regression model. Women characterized by earlier menarche (< or = 12 years) and longer period (> or = 8 days) were found to be associated with an elevated incurring risk, and a trend of increasing risk associated with primary dysmenorrhea (RR = 2.1 for mild to moderate and RR = 5.2 for severe dysmenorrhea), energetic physical activity during menstruation (RR = 2.1), and allergic diathesis (RR = 1.8) was seen. An inverse relationship was observed between the number of pregnancies and risk of endometriosis, and the protective effect was most significant when only the number of full-term pregnancies was counted. The risk factors of endometriosis are discussed, and intensive treatment of primary dysmenorrhea and avoidance of strenuous exercise during menstruation are identified as important measures in the prevention of endometriosis. PMID- 8000059 TI - A new functional classification of stomach cancer and its pathobiological and clinical significance. AB - The functional differentiations of stomach cancer specimens from 121 patients were investigated by enzyme-, mucin-, affinity- and immunohistochemical methods, and the stomach cancers were divided into five functionally differentiated types: 1) Absorptive Function Differentiation Type (AFDT), 19.8%; 2) Mucin Secreting Function Differentiation Type (MSFDT), 24.0%; 3) Absorptive and Mucin-Producing Function Differentiation Type (AMPFDT), 47.1%; 4) Special Function Differentiation Type (SFDT), 0.8%; and 5) Non-Function Differentiation Type (NFDT), 8.3%. The results indicate that stomach cancer tissues of the same histological type often display differing functional differentiation, and these functionally differentiated types have different invasive and metastatic characteristics. In addition, the functionally differentiated types have particular organic affinities of metastasis and different clinical prognoses. This study suggests that this new functional classification may supplement histological classification. The mechanisms of liver and ovary metastases of stomach cancer are also discussed. PMID- 8000060 TI - Gemfibrozil induced myositis: a case report with light microscopic and ultrastructural study. AB - A 49-year-old woman with chronic renal failure was given gemfibrozil for hyperlipidemia. She developed gemfibrozil-induced myositis which precipitated an acute compartment syndrome, necessitating emergency fasciotomy. The muscle biopsy showed prominent degeneration of the skeletal muscle fibers, associated with moderate chronic inflammatory infiltration. Electron microscopy revealed myofibrillary fragmentation and mitochondrial disorganization. The clinicopathologic features of gemfibrozil-induced myositis appear to be distinct from those of clofibrate-induced muscular syndrome. Extreme caution should be exercised in the use of gemfibrozil in patients with impaired renal function. PMID- 8000061 TI - Radiofrequency current catheter ablation of the left atrioventricular accessory pathways with paroxysmal supraventricular tachycardia. AB - Seventy patients with left atrioventricular accessory pathways and paroxysmal supraventricular tachycardia (PSVT) underwent radiofrequency catheter ablation (RFCA). The success rate was 94.3%. Among these patients, 26 had manifest preexcitation syndrome, and 44 had concealed preexcitation. Eighteen patients with concealed preexcitation underwent coronary sinus (CS) pacing, and delta wave appeared in 15. The keys to successful RFCA were correct positioning of the radiofrequency (RF) catheter tip, A/V amplitude ratio, AV interval (in sinus rhythm) and VA interval (during SVT or ventricular pacing). After 1-14 months of follow-up, two patients had supraventricular tachycardia (SVT) recurrence. PMID- 8000062 TI - A report of 39 cases of bronchioloalveolar carcinoma. PMID- 8000063 TI - High density cultivation of genetically-engineered CHO cell lines with microcarrier culture systems. AB - Genetically-engineered CHO cell lines, r beta-13 and CLF-8B2, were cultivated with the MC-1 microcarrier culture system. The cell density could be enhanced by increasing the concentration of microcarrier. At a microcarrier concentration of 10 mg/ml, the cell density could reach 4 to 5 x 10(6) cells/ml. It was shown that these cell lines would spontaneously release from the microcarrier to attach to and proliferate on fresh microcarriers. We were thus able to scale up cultivation using a simple method, i.e. by adding fresh microcarriers and medium directly into the culture system to about 2, 4 or 8 times the original volume. Using a perfusion culture system, we have successfully cultivated CLF-8B2 cells in a 2 L bioreactor for several weeks at medium perfusion rates of 0.5 to 3 working volumes. Prourokinase was stably secreted. PMID- 8000065 TI - Measurement of regional bone blood flow in the canine mandibular ramus using radiolabelled toad red blood cells. AB - Toad red blood cells were used to measure regional bone blood flow in the canine mandibular ramus. The blood cells were labelled with sodium pertechnetate and fixed in 10% formalin; they were 22 x 15 microns in size and had a specific gravity close to that of dog red blood cells. These cells had no discernible effect on systemic hemodynamics after injection, did not agglutinate, were well mixed and evenly distributed throughout the body, and were completely extracted in one circulation through the mandible. The mandibular ramus was divided into six regions, and the blood flow rates in each were found to be similar to those reported in previous studies with radiolabelled carbonized, microspheres. Furthermore, the blood flow distribution pattern of the mandibular ramus determined in this study was identical to that of our previous study using the bone-seeking radionuclide method. We suggest that radiolabelled toad red blood cells are an ideal marker for measuring regional blood flow in the canine mandible. PMID- 8000064 TI - Studies on the HDL receptors. I: Evidence for the existence of HDL receptors in Beijing duck liver. AB - It had been found that Beijing ducks (BD) have a high level of HDL (70%), high LCAT but very low CETP activity and will not develop atherosclerosis on an atherogenic diet, suggesting that cholesterol ester is mainly carried by HDL and metabolized through an HDL receptor pathway in the liver. However, evidence of this receptor's existence in the liver is not yet complete. In this paper, the HDL receptor in BD liver has been studied. Our experiments showed: 1) ApoE-free 125I-HDL could bind specifically to duck hepatic cell membrane with high affinity (Kd = 9.6 micrograms/ml) and was saturable (Bmax = 8.9 micrograms/mg cell membrane protein) at room temperature. 2) Competitive inhibition studies with unlabelled duck, human, rat and chick HDL and duck apo AI and its liposomes formed with PC or DMPC could inhibit the binding of 125I-HDL to duck hepatic cell membranes, but LDL, apo E and their liposomes with PC or DMPC could not with the exception of duck LDL. 3) The receptor could recognize apo AI but not apo B or E. 4) Both phosphorylase A2 and pronase could inhibit the binding activity. The above results give strong evidence for the existence of a specific HDL receptor pathway in the duck liver, supporting our hypothesis that CE in Beijing ducks is metabolized directly through the hepatic HDL receptor instead of being transferred back to VLDL and LDL, then through the LDL receptor pathway. This unique way of metabolizing CE may be behind the Beijing duck's antiatherogenicity. PMID- 8000066 TI - An immunocytochemical study of bone morphogenetic protein in experimental fracture healing of the rabbit mandible. AB - A monoclonal antibody raised against bone morphogenetic protein (BMP-McAb) has been used to demonstrate the presence of bone morphogenetic protein (BMP) in experimental fracture healing. Rabbit mandibles were fractured using standardized methods and left to heal for 3, 7, 14, 21 and 24 d, respectively. The avidin biotin complex (ABC) method demonstrated an accumulation of positively stained primitive mesenchymal cells at the fracture site in the hematoma stage of bone repair. These cells appeared to undergo differentiation into positively-stained chondroblasts and osteoblasts during the phase of callus formation. Undifferentiated mesenchymal cells showed a high positive reactivity in the early post-fracture stages but a much lower reactivity during the remodelling phase. The results of our study suggest that bone inductive processes are accompanied by the presence of BMP in osteoprogenitor cells during fracture healing of the mandible and that BMP may play a significant role in osteogenesis during bone healing. PMID- 8000067 TI - Different responses of choriocapillary endothelial cells and retinal capillary endothelial cells to mitogenic and vasoactive factors. AB - The responses of choriocapillary endothelial cells (CCE) and retinal capillary endothelial cells (RCE) in culture, in terms of phosphoinositide (PI) breakdown and cellular mitogenesis, to retinal pigment epithelial cell (RPE)-conditioned medium and vasoactive agents have been compared. RPE-conditioned medium did not induce PI breakdown in either type of cell. However, it stimulated DNA synthesis in CCE but not in RCE. Bradykinin (BDK) acted as both a fast signaling and a slow mitogenic factor on CCE, but BDK did not affect PI turnover or DNA synthesis in RCE. In contrast, thrombin stimulated PI turnover in RCE but not in CCE, though it did not induce 3H-thymidine incorporation into either type of cell. These differences in cellular functions between CCE and RCE following stimulation suggest that induction of DNA synthesis and receptor-mediated PI turnover by external factors is determined, at least in part, by the origin of the capillary endothelial cell. Therefore, extrapolation to CCE pathophysiology from experiments using endothelial cells from other capillary origins may not be valid. PMID- 8000068 TI - The challenge of infection control in an ageing population. PMID- 8000069 TI - Prospective study of decubitus ulcers in two long term care facilities. AB - The incidence and prevalence of decubitus ulcers, and their complications and microbiology were studied prospectively in two large long term care facilities in Winnipeg, Manitoba between January 1, 1989 and December 30, 1990. The initial prevalence of decubitus ulcers was 2.6 and 1.6% at the two institutions, with an incidence of 3.4 and 4.8 per 100,000 resident days, respectively. The incidence of decubitus ulcer infection was 1.4 per 1000 ulcer days. The only other complication identified was in one resident who required an indwelling catheter to permit ulcer healing. An average of 2.4 organisms grew from surface swabs of ulcers; anaerobes were isolated from 14% of cultures. Aspirates from clinically noninfected ulcers had bacteria isolated in 30% of specimens. Two-thirds of organisms isolated were considered potentially pathogenic. Concurrent bacteriuria was present for 75% of sampling episodes. Organisms present in the urine were simultaneously isolated from decubiti in only 5% of specimens. Decubitus ulcers are uncommon in long term care institutions. The urinary tract of the bacteriuric elderly appears to be an infrequent source of organisms colonizing decubiti. PMID- 8000070 TI - Myths surrounding the use of urinary catheters: a summary of key beliefs that inhibit acute care nurses from altering their use of urinary catheters. AB - Nurses frequently base their use and care of indwelling urinary catheters on long held beliefs that contemporary research is disproving. As an excellent place of attachment, the catheter permits rapid migration of organisms into the bladder, independent of the position of the catheter bag. For treatment of bladder distension, intermittent catheterization is preferable to leaving an indwelling catheter in place. Regardless of the amount of urine obtained, intermittent catheters are usually not intended to remain in the bladder. Irrigation of a bypassing urinary catheter forces organisms into the upper urinary tract. The process of irrigating blocked catheters (except for urology patients) is no longer the preferred intervention. Instead, catheters obstructed from prolonged use must be replaced with new ones or, whenever possible, left out. As a foreign device, urinary catheters in acute care must be recognized as a potential health threat. Indwelling urinary catheter must not be used for nursing convenience to ease heavy workloads, nor left in place as a result of patient coercion. PMID- 8000071 TI - Guidelines for control of meningococcal disease. The Laboratory Centre for Disease Control. PMID- 8000072 TI - Latex allergies project--April 1994. Health Canada-Health Protection Branch, Medical Devices Bureau. PMID- 8000073 TI - HIV transmission in out-patient setting in Australia. PMID- 8000074 TI - Molecular cloning of a Drosophila melanogaster gene coding for an homologue of human carboxypeptidase E. AB - PCR primers derived from two functional domains of vertebrate carboxypeptidase E (CPE) were used to generate a probe for screening a size-selected Drosophila melanogaster genomic library. A sequence representing about 50% of the expected complete sequence was obtained by translation of the two open reading frames present on a 1.6 kb DNA genomic fragment. This partial sequence, homologous to human CPE, CPM, and CPN, contained the conserved arginine and zinc binding domains. Similarities to the human enzymes were found with stretches that were equally divergent from the three vertebrate carboxypeptidases. Northern blot analysis revealed the presence of a 6.9 kb transcript for this gene in Drosophila embryos. I postulate that insects possess a single protein fulfilling CPE, CPM, and CPN functions. PMID- 8000075 TI - Purification and characterization of the Manduca sexta neuropeptide processing enzyme carboxypeptidase E. AB - The neuropeptide processing enzyme carboxypeptidase E (CPE) (E.C.3.4.17.10) has been well studied in vertebrates but its presence in invertebrates has not yet been reported. CPE activity in insects is present in membrane-bound and soluble forms. The soluble CPE has been purified to homogeneity from the brain of the tobacco hornworm Manduca sexta. It is a 57 kDa glycoprotein containing 9% sugars. It is activated 9.2 +/- 1.8 fold by CoCl2 and inhibited by chelating agents. Its sensitivity to guanidinoethyl-mercaptosuccinic acid, and its molecular mass, make this enzyme a good candidate to be the insect equivalent of the mammalian CPE. Furthermore, its lack of sensitivity towards p-(chloromercuri)benzenesulfonate puts it closer to the vertebrate carboxypeptidase M (CPM). We postulate that insects may possess a single protein fulfilling both CPE and CPM functions. PMID- 8000076 TI - Cytochrome b5 involvement in cytochrome P450 monooxygenase activities in house fly microsomes. AB - The involvement of cytochrome b5 in different cytochrome P450 monooxygenase and palmitoyl CoA desaturase activities in microsomes from insecticide-resistant (LPR) house flies was determined using a specific polyclonal antiserum developed against house fly cytochrome b5. Anti-b5 antiserum inhibited the reduction of cytochrome b5 by NADH-cytochrome b5 reductase. The antiserum also inhibited palmitoyl CoA desaturase, methoxycoumarin-O-demethylase (MCOD), ethoxycoumarin-O deethylase (ECOD), and benzo[a]pyrene hydroxylase (aromatic hydrocarbon hydroxylase, AHH) activities. However, methoxyresorufin-O-demethylase (MROD) and ethoxyresorufin-O-deethylase (EROD) activities were not affected by this antiserum. These results demonstrate that cytochrome b5 is involved in fatty acyl CoA desaturase activities and in certain cytochrome P450 monooxygenase activities (i.e., MCOD, ECOD, and AHH) in LPR house fly microsomes. Other cytochrome P450 monooxygenase activities (i.e., MROD and EROD) may not require cytochrome b5. The results suggest that cytochrome b5 involvement with cytochrome P450 monooxygenase activities is dependent upon the cytochrome P450 isoform involved. PMID- 8000078 TI - Generation and characterization of dihydroxycarbene, HO-C-OH, by neutralization/reionization mass spectrometry. AB - Dihydroxycarbene is produced in the gas phase by neutralization of the HO-C-OH+. radical cation which is formed by dissociative electron ionization of oxalic acid. Reionization approximately 0.3 microseconds later shows that HO-C-OH can survive intact and, thus, exists as a stable species with appreciable barriers for dissociation or rearrangement to formic acid (HCOOH). Within the time scale of the experiment, a small fraction of the carbene decomposes to H2O+CO. Comparison of the experimental results with ab initio theory shows that the dissociating HO-C-OH molecules are generated in the electronically excited triplet state, while the large amount of surviving carbene molecules is formed in the singlet ground state. PMID- 8000077 TI - Charge-remote fragmentation of peptides derivatized with 4 aminonaphthalenesulphonic acid. AB - A series of small peptides has been studied by negative-ion fast-atom bombardment mass spectrometry with collision-induced dissociation. It has been found that by derivatizing peptides with 4-aminonaphthalenesulphonic acid in a peptide linkage at the C-terminus, negative-ion formation can be enhanced and fragmentation in collision-induced dissociation reactions controlled. The peptide naphthalenesulphonates show charge-remote fragmentations and the resultant spectra give sequence information. PMID- 8000079 TI - Sequence-ion enhancement of peptides digested with proteinase K. AB - Proteinase K has been employed to proteolyze peptides before their mass spectrometric analysis. This combination of the two methods yields abundant sequence ions in the mass spectrum, thus leading to an easy prediction of the primary structure of the peptide. It was found that both the variety of available sequence ions and also their abundances are increased strongly after proteinase K digestion, when compared with the normal mass spectrum. The shortcoming of little fragmentation encountered using conventional mass spectrometric ionization methods can mostly be overcome. The H'n and Y"m ions produced from proteolysis provided a double check of the peptide sequence. PMID- 8000080 TI - Conjugation reactions of cyclodepsipeptide to glutathionyl adducts by direct 'in beam' synthesis under negative-ion fast-atom bombardment conditions. AB - The conjugation products of E-destruxin (cyclodepsipeptide) with glutathione have been identified by fast-atom bombardment mass spectrometry. Appropriate conditions were developed for cyclodepsipeptide substrate, which enabled the direct, dynamic mass spectra analysis of spontaneous as well as glutathione-s transferase catalyzed conjugation reactions. Application to the most active cyclopeptide in the series of destruxins yielded glutathionyl adduct. PMID- 8000081 TI - Improved ultrastructural preservation of rat ciliary body after high pressure freezing and freeze substitution: a perspective view based upon comparison with tissue processed according to a conventional protocol or by osmium tetroxide/microwave fixation. AB - Conventional fixation of the delicate, highly folded rat ciliary body and its iridial extension, as well as of vitreal structures, is associated with the induction of a number of artifacts, thus limiting the reliability of morphological interpretations. Improved ultrastructural preservation may be achieved by microwave heating in combination with osmium tetroxide fixation. This protocol, although simple and cheap, yields results, particularly with respect to the extracellular matrix compartment between inner and outer ciliary epithelial cells, which are not greatly inferior to those obtained by implementing the sophisticated high pressure freezing and freeze substitution technique. The latter affords good to very good ultrastructural preservation of epithelium and stromal components, such as blood vessels, neural elements, smooth muscle cells, fibrocytes, and free cells, up to a depth of 50-100 microns from the tissue surface. Its superiority over osmium tetroxide/microwave fixation is revealed in the cytoplasmic, intraorganellar, and vitreal matrix compartments, which incur no obvious losses. PMID- 8000082 TI - Correlated alkaline phosphatase histochemistry and quantitative backscattered electron imaging in the study of rat incisor ameloblasts and enamel mineralization. AB - The different functional conditions of pre-ameloblasts, secretory ameloblasts, and maturation ameloblasts in 9 day rat incisors were recognized using high resolution light microscopic alkaline phosphatase histochemistry: Digital backscattered electron imaging was performed using the block surfaces from which thin sections were taken for histochemical study. It was possible to correlate exact locations in histochemical sections with positions in the block face at all stages of enamel mineralization from early secretion through late maturation. The first steep increase in the rate of mineralization of completed enamel matrix occurs after the first transition from smooth ended ameloblasts to ruffle ended ameloblasts. In the 9 day rat incisors used for this purpose, there are only two smooth to ruffle cyclical transitions, and the width of successional smooth ended bands of ameloblasts in the maturation cycling process is always narrow. Nevertheless, there seems to be a good correlation between mineralization increase and the acquisition of the high alkaline phosphatase activity in the deeply enfolded distal cytoplasm of the ruffle-ended maturation stage ameloblasts. PMID- 8000083 TI - Fine structure of Tritrichomonas foetus as seen using cryotechniques. AB - Tritrichomonas foetus was studied using different physical and chemical fixation methods such as fast-freezing (by high pressure, "slam-freezing," and jet propane), freeze-substitution, conventional freeze-fracture and deep-etching, cryoultramicrotomy, and routine preparation for transmission electron microscopy. The use of fast-freezing fixation (FFF) proved to be superior in terms of structural preservation due to the rapidity of this fixation compared to that obtained using conventional chemical fixation. The low temperature techniques used here were useful to confirm data already obtained by conventional freeze fracture using chemical fixation and cryoprotection, such as the presence of flagellar rosettes and costa structure. Cryoultramicrotomy and slam-freezing also demonstrated the presence of hair-like structures projecting out from the protozoan surface. New aspects of organelles of T. foetus were demonstrated. PMID- 8000084 TI - Fabrication of Au/p-Si Schottky barrier for EBIC study. AB - A simple method for the fabrication of a Au/p-Si Schottky barrier suitable for electron beam induced current (EBIC) study has been developed. The mechanical and electrical properties of the fabricated Au/p-Si Schottky barriers have been tested, and EBIC measurements of the dislocation contrast have been conducted using the fabricated Schottky barriers. PMID- 8000085 TI - Preparation of isolated nuclei from K 562 haemopoietic cell line for high resolution scanning electron microscopy. AB - The aim of the work is to visualise nuclear pore complexes (NPCs) in mammalian cells by high resolution scanning electron microscopy. A detergent-free isolation protocol was employed to obtain clean nuclei from the haemopoietic cell line K 562. Nuclear isolation was performed by mechanical homogenisation under hypotonic conditions followed by purification of the nuclear fraction. The isolated nuclei were attached to silicon chips, fixed, critical point dried, and sputter coated with a thin film (3-4 nm) of tantalum. Analysis of the nuclear surface by scanning electron microscopy (SEM) revealed a strong sensitivity of the outer nuclear membrane (ONM) to disruption during the isolation procedure. A significant reduction of the characteristic pattern of damage to the ONM was achieved by means of an isopicnic centrifugation on an isoosmolar balanced Percoll gradient. Analysis of the population of isolated nuclei by flow cytometry showed no signs of cell cycle specific losses of nuclei during isolation. The SEM investigations of the morphology of the nuclear envelope (NE) and of substructural details of NPCs and polyribosomes were performed using an in-lens field emission scanning electron microscope. PMID- 8000086 TI - Three-dimensional organization of biological tissues: a new method for investigation using scanning electron microscopy. AB - A new method is described which enables the visualization of hidden cellular surfaces of biological tissues. The method does not depend on the kind of fixative solution, the duration of the fixation, or the quantity of extracellular matrix. The samples are chemically dissociated with potassium ethoxide until the first individual cells appear in the solution. This initial process is followed by phase contrast microscopy, and remaining tissue is investigated with scanning electron microscopy. The method has proved more effective than conventional enzymatic techniques and is a simple, quick, and effective way to investigate the three-dimensional organization of different normal and pathological tissues. PMID- 8000087 TI - Imaging of carbon nanoclusters by high-resolution scanning electron microscopy. PMID- 8000088 TI - The history and development of organ transplantation: biology and rejection. AB - In this chapter I have tried to survey organ transplantation from the point of view of a researcher who has been involved in the field since 1959. I have traced the two different lines of research--one, immunological and the other, surgical. To a large extent the surgical problems of transplantation have now been solved but rejection remains the main stumbling block to long-term survival of organ allografts. Immunological tolerance and defining rejection as an immune mechanism provided a background which was considered by immunologists to be hopeless from the point of view of clinical application. Surgeons, however, demonstrated the successful grafting of kidneys in identical twins. Then surgical observations clarified the different susceptibility of individual tissues to rejection, the liver being less likely to be rejected of the vital vascularized organs. An analysis of this phenomenon has been presented together with data on new powerful immunosuppressive drugs. Work in progress world wide is directed to the eventual establishment of tolerance in the clinic so that recipients of organ grafts will not have to submit to a lifetime of potentially toxic drug dosage. A shortage of organs for transplantation and the ethical dilemmas make organ transplantation an unusual and worrying field of medicine. Perhaps we will find salvation in transplanting organs from animals, although this achievement would seem to be some way off. PMID- 8000089 TI - Provision of transplant services. AB - To a large extent the success of any transplant programme depends ultimately on the expertise, skills and experience of the team of doctors, nurses and other health-care professionals. However, the logistics associated with the service will be the major factors determining the success of the programme. The service should be provided on the basis of epidemiological need, concentrating provision in an optimal number of units so that benefit is gained from the 'experience curve' effect of a relatively high throughput. The availability of the key resource for the programme, namely organs, depends on the willingness of the public to donate, and on the co-operation of other health-care professionals, not directly involved in transplantation, in identifying potential donors, encouraging relatives to consent and ensuring that the donor is maintained in an optimal condition. There are not many medical treatments that require such wide ranging participation and co-operation as those needed for organ transplantation. All these factors have to be addressed for an organ transplant programme to be successful. PMID- 8000090 TI - Assessing the benefits of transplant services. AB - This chapter presents some methods for the assessment of transplant benefits, using the example of liver transplantation. An independent assessment of the benefits of medical technology is especially important for evaluation of the balance between the costs and benefits involved. To enable comparison with other health-care facilities, benefits are defined in terms of a combination of life years gained and quality of life. The number of life-years gained can be calculated by comparing the survival expected with and without transplantation. Survival with transplantation is estimated on the basis of observed survival, acknowledging that the probability of survival may have changed over time, owing to changes in therapy and selection criteria. To estimate survival without transplantation, several techniques are available. Prognostic models, correcting for stage of disease, are often used. Pitfalls in the use of these models are discussed. The number of life-years gained can be corrected for quality of life by weighing survival with and without transplantation with an index representing quality of life. A method for the calculation of such an index is given. Finally, some cost estimates are presented and the results are discussed. PMID- 8000091 TI - Mechanisms of rejection. PMID- 8000092 TI - Xenografts: do they have a role? PMID- 8000093 TI - New immunosuppressive treatment in transplantation medicine. AB - Currently, the standard immunosuppressive regimen in organ transplantation is centred around cyclosporin. However, despite the use of this drug, rejection is not uncommon and it is associated with significant side-effects. Novel drugs and regimens have been developed to combat allograft rejection. Although FK506 has a similar mode of action and toxicity profile to cyclosporin, results, particularly in the rescue situation, have been encouraging. Sodium brequinar and rapamycin inhibit lymphocyte proliferation and may be most effective when used in combination with cyclosporin. Mycophenolate mofetil has been used in the treatment of psoriasis for many years; it is safe and will perhaps be useful in second-line therapy in patients unable to tolerate cyclosporin. The specific drugs highlighted in this chapter, although successful to differing degrees in preventing immunological rejection of allografts, have wide-ranging toxic effects on other organs in the body. Future use of these drugs is likely to utilize lower doses, supplemented by specific monoclonal antibody therapy, which can target diverse arms of the immune response. Large clinical trials using monoclonal antibodies against the T-cell receptor, the IL-2 receptor, CD4 T cells and specific adhesion molecules such as ICAM-1 are eagerly awaited. The number of new drugs and their mechanism of action, together with the widening spectrum of monoclonal antibodies available, will ensure that the next decade will be an exciting and hopefully profitable period in transplantation medicine. It is hoped that the introduction and assessment of these new agents will be rather more systematic and objective than that of their antecedents. PMID- 8000094 TI - Ethical issues in transplantation. AB - The transplantation of gastrointestinal organs has relied on cadaver donors for its successful development. The fact that success has been achieved is largely due to the certainty with which brain death can be diagnosed, and the acceptance of these criteria as signifying actual death by doctors, in particular, intensivists. If continuing goodwill leads to further co-operative effort, cadaveric liver, pancreas and eventually, small bowel transplants, should become more frequent. At present the numbers of recipients requiring these operations are considerably less than those in need of kidneys. There are grounds for believing therefore that the pressure to subvert good ethical standards in acquiring these organs (that pressure imposed by long waiting lists and a high death rate on those waiting lists) should be avoidable. The solution to the problem of deficits in cadaveric liver and pancreatic grafts will be achieved only by better education of nurses and doctors, professionalization and expansion of co-ordinator organizations, legal reform, and cultural change. Only by such progress, achieved at medical, governmental, and societal levels can we avoid the insidious tendency to commercialism which we have witnessed with disquiet in renal transplantation. PMID- 8000095 TI - Liver transplantation: newer surgical approaches. AB - The standard procedure for orthotopic liver transplantation remains transplantation of the whole organ together with resection of the vena cava and the use of venovenous bypass. In cases of severe mismatch of the donor and recipient vena cava, the piggyback technique, if necessary with vena cava plasty, is preferable. Furthermore, in all cases where venovenous bypass cannot be performed, the piggyback or other technique preserving the vena cava should be performed. In paediatric patients, reduced/size liver transplantation may be indicated because of the shortage of small livers. In the hands of experienced surgeons, the results of reduced-size liver transplantation in paediatric patients are similar to those of whole organ transplantation. Further innovative procedures to overcome the problem of organ shortage include split-liver and living related transplantation in children. Distinct advantages of living related transplantation can be seen in a well-functioning graft, lack of preservation injury, elective operation and optimal graft-size matching. The immunological advantage that has been claimed could not be demonstrated so far, and will need to be examined in the long-term follow-up. However, there remains a distinct disadvantage for living related transplantation with regard to the surgical technique. Preoperative portal venous thrombosis should be carefully assessed, but is not a contraindication to liver transplantation if the confluence of the superior mesenteric vein and splenic vein is patent. Arterial reconstruction at the confluence of two arteries (hepatic and gastroduodenal or splenic artery) seems to be preferable to an end-to-end anastomosis because of improved inflow into the graft and a reduced risk of arterial stenosis and thrombosis. Where the common hepatic arteries are small, with reduced or reversed flow, and in patients with coeliac trunk stenosis, we recommend a direct approach to the suprarenal or infrarenal aorta. Bile duct anastomosis may preferably be performed with a side to-side technique, to reduce early and late biliary complications. PMID- 8000096 TI - Changing indications in liver transplantation. AB - During the last decade orthotopic liver transplantation has become virtually a routine procedure and most centres are reporting, in elective cases, survival rates at 1 year in excess of 90%. As experience with liver transplantation has grown, attention has focused more on refining the indications for transplantation and determining the optimal time for the procedure. In patients with fulminant hepatic failure, it may still be difficult to select those patients who require liver replacement early enough in their illness so that a suitable organ can be found and the procedure carried out before the onset of irreversible complications. Alternatives to orthotopic liver transplantation, including liver support, heterotopic transplantation, partial orthotopic liver transplantation and xenografting, are being assessed. Progress too has been made in improving indications in patients undergoing transplantation for viral hepatitis and alcoholic liver disease. Nonetheless, liver replacement remains a poor substitute for prevention of end-stage liver disease. Even with advances made in immunosuppression, there are long-term sequelae as a consequence of liver transplantation, and now more recently attention is being paid to reducing the toll of immunosuppressive drugs. PMID- 8000097 TI - Techniques of pancreas and islet transplantation. AB - Techniques for vascularized pancreas transplantation are relatively standardized, whereas those for human islet isolation and transplantation are rapidly changing and evolving. The commonest method for transplanting the vascularized pancreas is to use the entire pancreas together with a segment of donor duodenum, and to anastomose this to the recipient bladder. This technique offers the advantages of technical ease, the maximum beta-cell mass is transplanted and graft function can be monitored by measuring urinary amylase levels. Human islet isolation requires that the pancreas is dissociated, the islets purified and then transplanted to a well-vascularized location. The pancreas is dispersed by a combination of the intraductal injection of collagenase and gentle mechanical agitation, and the islets separated from contaminating exocrine tissue by density-gradient centrifugation. Once purified, the islets can be placed into tissue culture or cryopreserved. The commonest site for human islet transplantation is intraportal injection so that the islets are embolized throughout the liver. Alternatives include transplantation to the renal subcapsular space or the spleen. PMID- 8000098 TI - Pancreatic transplantation: indications and results. PMID- 8000099 TI - Small bowel transplantation. PMID- 8000100 TI - A review of neuromotor tests and the construction of a scored neuromotor examination for four-year-olds. AB - We have reviewed the methodologies in construction of some widely used tests and constructed a computer-compatible scored method for the neuromotor evaluation of four year olds. Using the data from 333 neurological assessments, factor analysis indicated five subscales. Alpha coefficients show high reliability for both subscales and total scores. Using data from a second sample, we describe predictive validity for the five subscales and total score. PMID- 8000101 TI - Selegiline (L-deprenyl) and L-dopa treatment of Parkinson's disease: a double blind trial. AB - To confirm the clinical utility of selegiline (L-deprenyl), a selective inhibitor of monoamine oxidase B, as an anti-Parkinson's disease (PD) agent, the first Japanese multi-center, double-blind comparative study of this drug was conducted. The subjects were patients who had responded poorly or suffered with other problems related to L-dopa treatment. A total of 112 patients in two groups, one given selegiline at a dose of 7.5 mg/day (Group D, n = 60) and another given a placebo (Group P, n = 52), were compared over an 8-week treatment period. The percentage patients showing "moderate improvement" or better was 34.5% in Group D, while that in Group P was 11.5% (P < 0.01). In the assessment of overall safety, 66.7% in Group D showed no adverse reactions, which was not significantly different from the result of 78.9% for Group P. PMID- 8000102 TI - Radiographic and hemodynamic changes during recovery from high-altitude pulmonary edema. AB - It has been suggested that accentuated pulmonary hypertension is a contributing factor in the development of high-altitude pulmonary edema (HAPE). The purpose of this study was to evaluate the chest radiographic features associated with pulmonary hemodynamic changes in HAPE. We studied 16 patients with HAPE using posteroanterior chest roentgenograms taken in the standing position both on admission and following recovery. The cardiothoracic ratio (CTR) as well as the area and volume of the main pulmonary artery were measured. During HAPE, we found slight enlargement of the CTR, especially the right ventricle, and prominence of the main pulmonary artery. These abnormalities significantly improved in the recovery state. The changes in area and volume of the main pulmonary artery were closely correlated with a decrease in CTR during recovery from HAPE, and correlated with the pulmonary hemodynamic changes observed by right heart catheterization (n = 4). Radiographic changes reflect the alterations in pulmonary hemodynamics in patients with HAPE. PMID- 8000103 TI - Pulmonary infection due to Mycobacterium xenopi. AB - We describe two cases of pulmonary infection due to Mycobacterium xenopi (M. xenopi). Both cases were men, ages 61 and 54 yr. In the first patient, lung infection due to M. xenopi occurred after gastrectomy. The second patient had an inactive M. tuberculosis infection. Both had pulmonary symptoms including cough, sputum and fever. Each chest X-ray showed an infiltrative shadow with a cavity in a unilateral, upper lobe. Isolates from both patients were studied not only by microbiological characteristics but also by DNA-DNA hybridization. All isolates were susceptible to streptomycin and kanamycin. In the first case, the patient had initially received rifampicin, isoniazid and ethambutol despite in vitro susceptibility patterns, however, there was no response and a new infiltrative shadow appeared in the contralateral lobe. With a multiple drug regimen based on in vitro susceptibility, clinical and roentgenographic improvements were achieved. The second patient showed a favorable response to the initial chemotherapy. Pulmonary infection due to M. xenopi can generally be successfully treated with drugs to which the organisms show in vitro sensitivity. We also reviewed the other two cases reported in Japan. PMID- 8000104 TI - Pulmonary hypertension in systemic lupus erythematosus: a report of an autopsied case. AB - An autopsied case of systemic lupus erythematosus with pulmonary hypertension is reported. A 29-year-old woman with a seven-year history of polyarthralgia, butterfly rash, nephrotic syndrome and Raynaud's phenomenon was admitted because of progressive dyspnea on exertion. Tests for antinuclear antibody, anti cardiolipin antibody and lupus anticoagulant were positive. Echocardiographic examination revealed right ventricular hypertrophy and a moderate pericardial effusion. Estimated systolic pulmonary arterial pressure was 53 mmHg. Despite treatment with corticosteroids including pulse methylprednisolone therapy, lipo PGE1 and warfarin, she died of progressive congestive heart failure. Postmortem examination of the pulmonary vasculature revealed findings consistent with plexogenic pulmonary arteriopathy, without evidence of vasculitis, fibrinoid necrosis, or thromboemboli. PMID- 8000105 TI - A MELAS (mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes) mtDNA mutation that induces subacute dementia which mimicks Creutzfeldt Jakob disease. AB - A 50-year-old woman with subacute dementia and brain atrophy on CT showed periodic synchronous discharge (PSD) on electroencephalogram (EEG) and myoclonus. She was initially suspected of suffering from Creutzfeldt-Jakob disease (CJD), but dramatically recovered over 5 months. Based on further investigations, the final diagnosis was mitochondrial encephalomyopathy with an A-to-G substitution at nucleotide position 3243 in mitochondrial DNA (mtDNA), commonly seen in patients with mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke like episodes (MELAS). This case suggests that patients suspected of suffering from CJD should be evaluated for mitochondrial encephalomyopathy. PMID- 8000106 TI - Marked elevation of carcinoembryonic antigen and carbohydrate antigen 19-9 in the peripheral blood as an initial manifestation of meningeal carcinomatosis. AB - Marked elevation of tumor markers in the peripheral blood was initially a sole manifestation of meningeal carcinomatosis in a man with gastric carcinoma. In addition to extensive meningeal carcinomatosis, no metastatic lesions were found at autopsy other than microscopic infiltration into a tiny paraaortic lymph node. Elevation of these markers in the peripheral blood is best explained by meningeal carcinomatosis. When elevation of these markers is otherwise unexplainable, meningeal carcinomatosis should be considered as a diagnostic possibility even in the absence of neurological symptoms. PMID- 8000107 TI - Pulmonary infiltration with eosinophilia and increased serum levels of squamous cell carcinoma-related antigen and neuron specific enolase. AB - We report a case of pulmonary infiltration with eosinophilia (PIE), associated with increased serum levels of squamous cell carcinoma-related antigen (SCC) and neuron specific enolase (NSE). The diagnosis of PIE was confirmed by examination of bronchoalveolar lavage fluid and specimens of transbronchial lung biopsy. It was suggested that PIE was probably induced by a course of amoxicillin for a sore throat. Corticosteroid therapy resulted in clinical improvement of symptoms, resolution of pulmonary infiltrates on chest roentgenogram and reduction in serum levels of SCC and NSE. PMID- 8000108 TI - Atypical peritracheobronchial vasculitis and an effective treatment. AB - We report an interesting case of vasculitis in which the inflammatory lesion was limited to the peritracheobronchus. This case showed positive antineutrophil cytoplasmic antibodies, diffuse peritracheobronchial swelling, and vasculitis in its histology. Steroid therapy was effective for both roentgenological and serological findings. Although the biopsy specimen shows only inflammation and does not satisfy the WHO criteria of Wegener's granulomatosis (WG), a possible diagnosis of WG should not be disregarded. PMID- 8000109 TI - Progressive systemic sclerosis complicated with primary cerebral malignant lymphoma. AB - We describe a 68-year-old man who developed primary cerebral malignant lymphoma 5 years after the onset of progressive systemic sclerosis (PSS). There was no association with Sjogren's syndrome. This is the first report of PSS complicated with primary cerebral malignant lymphoma. PMID- 8000110 TI - Insulin resistance in a patient with diabetes mellitus associated with Turner's syndrome. AB - We evaluated insulin resistance and assessed the effect of gliclazide on insulin resistance in a patient with diabetes mellitus associated with Turner's syndrome. Insulin-induced glucose metabolism markedly decreased compared with 12 healthy subjects. The insulin dose-response curve of this patient shifted to the right and down, and recovered somewhat after the administration of gliclazide. This patient had exhibited marked insulin resistance, which seemed to be caused by a defect at the receptor and/or post-receptor levels. Gliclazide reduced her insulin resistance, which suggests that this agent is suitable for treating the insulin resistance in diabetic patients with Turner's syndrome. PMID- 8000111 TI - Development of Graves' ophthalmopathy and uveitis after radioiodine therapy for Graves' disease in a patient with HTLV-I associated myelopathy (HAM). AB - HTLV-I carriers or patients with HTLV-I associated myelopathy (HAM) are prone to immune-mediated inflammatory disorders. We present a 44-year-old female with HAM who developed Graves' disease. She developed severe Graves' ophthalmopathy shortly after 131I therapy, concurrently with a remarkable increase in TSH receptor antibody titer. Ophthalmopathy was aggravated in spite of prednisolone therapy and euthyroidism being maintained by thyroxine replacement. Uveitis also developed after 131I therapy and iridocyclitis finally required trabeculotomy. This case suggests that HAM patients may have a higher risk of immune-mediated Graves' ophthalmopathy after 131I therapy. PMID- 8000112 TI - Goodpasture's-like syndrome and effect of extracorporeal membrane oxygenator support. AB - A 49-year-old man was admitted because of general fatigue, cough and hematuria. During the hospital course, acute renal failure, hemoptysis and dyspnea developed. A percutaneous renal biopsy revealed a diffuse crescentic glomerulonephritis, and direct immunofluorescence showed a linear pattern of IgG along the glomerular basement membrane. Although serum anti-glomerular basement membrane (anti-GBM) antibody was not detected. Goodpasture's-like syndrome was suspected, and methylprednisolone pulse therapy and plasmapheresis were administered. Concomitantly, extracorporeal membrane oxygenation (ECMO) was instituted because of deterioration in respiratory status due to a severe pulmonary hemorrhage despite maximal ventilatory support. Temporarily, the patient improved and ECMO was discontinued. ECMO may be a useful therapeutic support for hypoxia resulting from pulmonary hemorrhage in Goodpasture's syndrome (GPS) and Goodpasture's-like syndrome. PMID- 8000113 TI - Cavernous lymphangioma of the spleen in a patient with Klippel-Trenaunay-Weber syndrome. AB - A 31-year-old woman presented with hypertrophy of the left upper extremity and thrombocytopenia. Physical examination revealed splenomegaly, and laboratory investigation revealed thrombocytopenia, elevation of cross-linked fibrin degradation products (XDP), and thrombin-antithrombin III complex (TAT). A diagnosis of Klippel-Trenaunay-Weber (K-T-W) syndrome was established by the dermatologic findings and angiography of the extremities. A splenic cavernous lymphangioma was diagnosed by ultrasonography and angiography, and was confirmed by pathology following splenectomy. Post-operatively, the platelet count increased, and hemostatic parameters normalized. Cavernous lymphangioma is a rare complication of Klippel-Trenaunay-Weber syndrome. Splenectomy proved to be an effective therapy for both cavernous lymphangioma and consumptive coagulopathy in Klippel-Trenaunay-Weber syndrome. PMID- 8000114 TI - Medical management of peripheral arterial disease. AB - Patients with atherosclerotic peripheral arterial disease (PAD) of the lower extremities have an inadequate blood flow to exercising muscle. This results in a walking impairment due to intermittent claudication (exercise-induced cramping in the muscles of the lower extremities). Persons with PAD are at increased risk of cardiovascular events, with an excess mortality from strokes and myocardial infarction. The medical treatment of patients with PAD is directed at intensive risk factor modification to decrease cardiovascular morbidity and mortality. A second treatment goal is to improve exercise performance and functional capacity. To this end, a limited number of drugs have been developed to improve claudication symptoms. In addition, the nonpharmacologic treatment of claudication includes exercise rehabilitation. Previous studies have shown that an exercise rehabilitation program results in significant increases in treadmill peak walking time, peak oxygen consumption, and pain-free walking time. Patients also reported improved walking ability and functional status in the community setting. Therefore, optimal treatment of this patient population includes cardiovascular risk factor modification, selective use of claudication drugs, and exercise rehabilitation. PMID- 8000115 TI - Percutaneous transluminal angioplasty of the abdominal aorta. AB - PURPOSE: To determine the long-term results of percutaneous transluminal angioplasty (PTA) of focal infrarenal abdominal aortic stenoses. PATIENTS AND METHODS: Over a 10-year period, 15 focal infrarenal abdominal aortic stenoses were treated with PTA in 14 patients (13 women and one man; mean age, 53.2 years; range, 43-78 years). RESULTS: The initial technical success rate was 100%. Clinical patency, as defined by continued absence or improvement in symptoms after PTA, was achieved in 14 of the 15 angioplasty procedures (93%) with a mean duration of clinical follow-up of 4.3 years (range, 0.6-9.8 years) in the 14 patients. Long-term noninvasive follow-up demonstrated continued patency of the angioplasty site in 11 of 11 patients available for study. The mean ankle-arm index in these 11 patients was 0.95 (range, 0.9-1.0) at a mean follow-up of 4.8 years (range, 0.6-9.8 years). There was no significant morbidity or mortality associated with the angioplasty procedures. CONCLUSION: In view of the high degree of technical success and the excellent long-term patency, we believe that PTA should be considered a primary method of treatment in properly selected patients with focal abdominal aortic stenoses. PMID- 8000116 TI - Subintimal versus intraluminal laser-assisted recanalization of occluded femoropopliteal arteries: one-year clinical and angiographic follow-up. AB - PURPOSE: To compare the prolonged effect of subintimal versus intraluminal recanalization of occluded femoropopliteal arteries. PATIENTS AND METHODS: Recanalization of an occluded femoropopliteal artery was attempted in 63 patients (51 men, 12 women; mean age, 63 years) with lifestyle-limiting claudication and at least one patent distal artery. After assessment of baseline clinical and angiographic variables, mechanical passage was first attempted with use of a laser catheter with a 2.2-mm- diameter hemispherical contact probe that was connected to a neodymium: yttrium-aluminum-garnet laser. In case of failure, the laser was activated at 1-second pulses of 15 W. In some cases additional guide wire and catheter manipulations were used. Successful recanalization was followed by standard balloon dilation. An intense antithrombotic regimen was used. RESULTS: The occluded artery could be entered in 62 of 63 patients. The catheter was assumed to have followed a subintimal course in 20 patients (group A) and an intraluminal course in 42 patients (group B). Successful recanalization was achieved in 17 patients (85%) of group A and in 36 (86%) of group B. No significant differences were found in clinical and angiographic follow-up measurements between the two groups. The angiographic cumulative primary patency rate (open vs closed) at 1 year was 93% +/- 6 in group A and 93% +/- 4 in group B. The cumulative restenosis/reocclusion-free patency rate was 63% +/- 13 and 65% +/- 9 for groups A and B, respectively. Median length of the original occlusion (8.0 cm in group A vs 4.5 cm in group B) was the only distinguishing baseline variable between the groups (P < .02) and was also the single independent predictor of recurrent flow limitation (P = .0017). Significant complications were distal embolization in three patients, followed by death in one patient and puncture site bleeding in two patients. CONCLUSION: The 1-year clinical and angiographic results of assumed subintimal and intraluminal recanalization are comparable. Thus, a subintimal course per se should not be regarded as a failure of the procedure. PMID- 8000117 TI - Hepatic arterial occlusion and dissection: treatment with intravascular stents. PMID- 8000118 TI - Stent placement for iliac artery occlusions: modified "wire-loop" technique with use of the goose neck loop snare. PMID- 8000119 TI - Acute stroke intervention with intraarterial urokinase infusion. AB - PURPOSE: A preliminary evaluation of the efficacy and safety of treating patients with acute stroke with intraarterial urokinase infusions was performed. PATIENTS AND METHODS: Twelve patients with acute stroke were treated within 8 hours of symptom onset (average, 5 hours). Thrombolysis was performed within the middle cerebral (n = 10), internal carotid (n = 1), and basilar (n = 1) arteries. Urokinase (160,000-500,000 IU) was infused through microcatheters placed into or adjacent to the thrombi. RESULTS: Thrombolysis was angiographically successful in nine patients (75%), all of whom had long-term neurologic improvement. No or minimal neurologic deficits were present in six patients (50%). Thrombolysis failed in three patients (25%); one patient died and two developed severe permanent neurologic deficits. No hemorrhagic complications occurred. CONCLUSION: Preliminary results suggest that intraarterial urokinase infusion may be effective and safe for treating patients with acute stroke. Potentially devastating neurologic damage was averted or lessened in nine patients (75%). No additional neurologic damage was caused by intervention in the remaining three patients (25%). PMID- 8000120 TI - Mechanical thrombectomy with the Amplatz device: human experience. AB - PURPOSE: The authors present their early experience of mechanical arterial and graft thrombectomy with the Amplatz thrombectomy device. PATIENTS AND METHODS: Preliminary data are presented for 14 patients treated with the Amplatz thrombectomy catheter. The procedure was carried out in 10 arterial polytetrafluorethylene grafts, in two native arteries, and in two patients with venous thrombosis. RESULTS: The thrombectomy catheter completely removed the clot in 11 patients and partially removed clot in three patients. Mean thrombectomy time was 2 minutes 45 seconds. Despite distal blood pressure cuff occlusion, two instances of insignificant distal embolization occurred. Mechanical clot dissolution has consistently produced hemolysis without adverse clinical effects. The underlying causative factors such as stenoses were treated by means of angioplasty, atherectomy, or surgical endarterectomy. CONCLUSION: Mechanical thrombectomy with this device is a new, effective technique and can rapidly remove the thrombus. From preliminary results, the device seems most promising in clearing out thrombi in occluded synthetic femoral-to-popliteal bypass grafts. The device could have wider application if it were steerable and if it could be introduced from the contralateral approach. PMID- 8000121 TI - Recurrent thrombosis of polytetrafluoroethylene dialysis fistulas after recent surgical thrombectomy: salvage by means of thrombolysis and angioplasty. AB - PURPOSE: To test the hypothesis that thrombolysis followed by angioplasty for salvage of thrombosed polytetrafluoroethylene (PTFE) dialysis fistulas is safe and effective even after recent surgical thrombectomy. MATERIALS AND METHODS: Thrombolysis and balloon angioplasty were performed on 12 fistulas in which thrombosis had recurred within 30 days after thrombectomy (n = 10) or thrombectomy/revision (n = 2). All patients underwent pulse-spray pharmacomechanical thrombolysis with urokinase and use of a crossed-catheter technique. A total of 250,000-1,000,000 IU of urokinase and 2,500 IU of heparin were injected throughout the clot in 17-33 minutes. A bolus of 2,500 IU of heparin was simultaneously administered intravenously. RESULTS: Thrombolysis was successful in restoring flow in all grafts, but thrombosis recurred in three grafts before they could be used for dialysis. The clinical success rate was thus 75%. There were no major complications. Mean primary patency after thrombolysis in this small select group of patients was 94 days (median, 68.5 days), comparing favorably with the mean patency of 44 days (median, 23 days) achieved by the prior 23 surgical revisions in the same grafts. CONCLUSION: Percutaneous fistula salvage appears to be a safe and effective means of treating recurrent thrombosis in PTFE dialysis fistulas when recent surgical thrombectomy has failed. PMID- 8000122 TI - Drug delivery into the arterial wall: a time-course study with use of a lipophilic dye. AB - PURPOSE: One potential approach to the prevention of restenosis after angioplasty is to deliver antiproliferative agents directly to the angioplasty site. The purpose of this study was to determine the time course of drug penetration into the media of the balloon-dilated artery. MATERIALS AND METHODS: Balloon angioplasty of the left and right iliac arteries was performed once for 1 minute in each of five rabbits. A double-balloon catheter was then positioned at the site of angioplasty, and the fluorescent dye PKH26 (molecular weight, 961) was delivered under pressure to simulate drug delivery. Afterward, the arteries were removed and dye penetration into the media was measured on frozen cross sections by epifluorescence microscopy. RESULTS: Delivery of the dye was performed for periods ranging from 5 to 50 minutes at a mean pressure of 189 mm Hg. The depth of dye penetration (D, micrometers) was directly related to dye perfusion time (T, minutes) (D = 0.348T + 11.958, r = 0.496, P < .01). This equation predicts complete medial dye penetration in 81 minutes assuming an average intima-media thickness (40 microns). CONCLUSION: This study demonstrates that PKH26 can be delivered to the media of the dilated artery. However, the time required to obtain complete penetration may limit the utility of this double-balloon catheter approach to drug delivery. PMID- 8000123 TI - Stent-induced intimal hyperplasia: are there fundamental differences between flexible and rigid stent designs? AB - PURPOSE: To evaluate possible differences in neointimal development resulting from overdilation of rigid versus flexible vascular stents. MATERIALS AND METHODS: Twelve vascular sheaths were placed bilaterally through femoral arteries in six swine. After angiographic measurement, 12 stents (six flexible and six rigid) were balloon expanded to 8-mm diameters in 12 6-mm iliac arteries (approximately 30% overdilation). All stents were similar in surface area, gauge, and type of wire (tantalum). The primary difference was longitudinal flexibility (low hoop strength) versus rigidity (high hoop strength). Stents were studied with angiography and intravascular ultrasound 5 weeks after implantation. The animals were killed, and the stented segments were removed and examined histologically. RESULTS: Rigid stents maintained larger diameters than flexible stents: mean, 6.52 mm versus 5.82 mm (mean difference, 0.70; standard deviation [SD], 0.47; confidence interval [CI], +/- 0.49; P < .05). In addition, rigid stents developed a thicker, eccentric neointimal reaction relative to flexible stents: mean 1.08 mm versus 0.74 mm (mean difference, 0.338; SD, 0.315; CI, +/- 0.331; P < .05). CONCLUSION: Rigid stents maintain larger diameters over the long term relative to flexible stents when overdilated in normal swine arteries. However, a thicker neointima develops within the lumen of rigid stents at follow up (greater late loss). PMID- 8000124 TI - Strength, elasticity, and plasticity of expandable metal stents: in vitro studies with three types of stress. AB - PURPOSE: Five types of expandable metal stents (Palmaz, Strecker, Gianturco, Cragg, and Wallstent) were subjected to standardized tests to obtain objective, comparable data of their mechanical characteristics. MATERIALS AND METHODS: The stents were subjected to area loads, point loads, and circular loads; the resistance of the stents to a continually increasing deformation was measured. Elasticity and deformation characteristics of the stents were also noted. Another experiment simulated the situation of the stent in an implanted state. The stents were covered with a thin self-adhesive foil to simulate optimal wall contact by limiting the mobility of the mesh struts. RESULTS: For all types of stress, the Palmaz stent showed the highest resistance but was completely inelastic. The Strecker stent and the Wallstent showed higher resistance when coated in foil (simulating good wall contact). The Gianturco stent showed the lowest resistances but was completely elastic. A point load on a Wallstent caused concentric constriction over a longer distance. CONCLUSIONS: Palmaz stents are appropriate for insertion into highly resistant obstructions. Strecker stents and Wallstents require good wall contact to achieve adequate strength. Because of their unique deformation characteristics, Wallstents may not function well if implanted into eccentric stenoses of tough consistency. The Gianturco stent showed the lowest resistances. PMID- 8000125 TI - Percutaneous bilio-cholecystic bypass. PMID- 8000126 TI - Biliary manometry versus clinical trial: value as predictors of success after treatment of biliary tract strictures. AB - PURPOSE: To evaluate the biliary manometric-perfusion test (BMPT) and clinical trial as predictors of long-term success after percutaneous and surgical treatment of biliary tract strictures. PATIENTS AND METHODS: After percutaneous intervention or surgical repair of extrahepatic bile duct strictures, 43 patients underwent long-term biliary intubation (mean, 13 months) with 61 internal external stents. Before removal of the stents, all 43 patients underwent a BMPT (n = 65) and 24 underwent a 2-3-week clinical trial (n = 27) with stents positioned above the treated region. Patients were followed up 1-46 months (mean, 16 months) after stent removal, with clinical outcome determined by means of physical examination, biochemical evaluation, chart review, and telephone interview. RESULTS: With logistic regression analysis, the BMPT and clinical trial were shown to have equal predictive value in determining treatment success or failure. Eighty-four percent of the clinical outcomes were correctly predicted with BMPT, versus 88% for the clinical trial. Kaplan-Meier survival curve analysis demonstrated the probability of remaining stricture free at 1 year after passing a BMPT and after passing a clinical trial to be 90% and 86% (P = .55), respectively. CONCLUSION: BMPT and clinical trial have similar capabilities in the prediction of long-term patency after treatment of benign biliary tract strictures, but the BMPT is less costly and time consuming for the patient. PMID- 8000127 TI - Chemical ablation of the gallbladder: evaluation of multiple agents in vitro. AB - PURPOSE: To find a more effective chemical regimen for transcatheter ablation of the gallbladder in an in vitro model. MATERIALS AND METHODS: Sectioned and whole pig gallbladders were exposed in vitro to 12 different chemical solutions at varying conditions of exposure time, pH, and temperature. RESULTS: In the in vitro studies, 0.1 N and 1.0 N solutions of sodium hydroxide in water or ethanol and 3% hydrogen peroxide were the most effective sclerosant agents. Ethanol and hydrochloric acid failed to completely eliminate the epithelium from the gallbladder sections. Increasing exposure time from 10 to 20 minutes or increasing the temperature of the solutions from 37 degrees C to 50 degrees C did not alter these results. Sequential 15-minute exposures to 0.1 N sodium hydroxide in ethanol followed by peroxide completely eliminated the epithelium from whole gallbladders in vitro. CONCLUSION: Alkaline solutions and hydrogen peroxide are more effective than ethanol alone, acids, or detergents in eliminating gallbladder epithelium in this model. Further evaluation of these agents in vivo is merited. PMID- 8000129 TI - Intraaortic biopsy of a primary aortic tumor. PMID- 8000128 TI - Comparison of diagnostic accuracy with carbon dioxide versus iodinated contrast material in the imaging of hemodialysis access fistulas. AB - PURPOSE: Imaging of dialysis fistulas was performed with use of carbon dioxide and iodinated contrast material. Images were then compared to assess the quality and accuracy of CO2 as a contrast agent. PATIENTS AND METHODS: Thirty-two patients underwent digital subtraction imaging of the fistulas performed with both iodinated contrast material and CO2 to evaluate the venous anastomosis. The images were blinded and the degree of stenosis was graded in 10% increments by two physicians. Statistical analysis including sensitivity, specificity, and accuracy of CO2 images was performed. RESULTS: There was no significant difference in physician ratings of the degree of venous stenosis (P > .30). Estimation of the degree of stenosis was significantly higher with CO2 than with ionic contrast material (P = .0001). When iodinated contrast material is used as the gold standard, the sensitivity, specificity, and accuracy of CO2 were 94%, 58%, and 75%, respectively. CONCLUSIONS: CO2 has a role as a contrast agent in the imaging of dialysis access grafts when the use of iodinated contrast material is of concern. CO2 is safe for venous injections; however, it should not be used to evaluate the arterial anastomosis with the "reflux technique." PMID- 8000130 TI - Single-step balloon dilation of postoperative pyloric stenosis: benefit of large balloon technique. PMID- 8000131 TI - Evulsion of a Vena Tech filter during insertion of a central venous catheter. PMID- 8000132 TI - Rigors with thrombolysis. PMID- 8000133 TI - Prophylaxis with urokinase thrombolysis. PMID- 8000134 TI - How is it that microsatellites and random oligonucleotides uncover DNA fingerprint patterns? AB - Minisatellites, microsatellites, and short random oligonucleotides all uncover highly polymorphic DNA fingerprint patterns in Southern analysis of genomic DNA that has been digested with a restriction enzyme having a 4-bp specificity. The polymorphic nature of the fragments is attributed to tandem repeat number variation of embedded minisatellite sequences. This explains why DNA fingerprint fragments are uncovered by minisatellite probes, but does not explain how it is that they are also uncovered by microsatellite and random oligonucleotide probes. To clarify this phenomenon, we sequenced a large bovine genomic BamHI restriction fragment hybridizing to the Jeffreys 33.6 minisatellite probe and consisting of small and large Sau3A-resistant subfragments. The large Sau3A subfragment was found to have a complex architecture, consisting of two different minisatellites, flanked and separated by stretches of unique DNA. The three unique sequences were characterized by sequence simplicity, that is, a higher than chance occurrence of tandem or dispersed repetition of simple sequence motifs. This complex repetitive structure explains the absence of Sau3A restriction sites in the large Sau3A subfragment, yet provides this subfragment with the ability to hybridize to a variety of probe sequences. It is proposed that a large class of interspersed tracts sharing this complex yet simplified sequence structure is found in the genome. Each such tract would have a broad ability to hybridize to a variety of probes, yet would exhibit a dearth of restriction sites. For each restriction enzyme having 4-bp specificity, a subclass of such tracts, completely lacking the corresponding restriction sites, will be present. On digestion with the given restriction enzyme, each such tract would form a large fragment.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8000136 TI - A single linkage group comprising 11 polymorphic DNA markers on rat chromosome 3. AB - Eleven polymorphic DNA markers were mapped to rat Chromosome (Chr) 3 by linkage analysis of F2 progeny of F344/N and LEW/N rat strains. The markers, including seven genes and four anonymous loci, formed a single linkage group covering approximately 112 cM with the following order: Ptgs1 (prostaglandin G/H synthase I)-D3Arb178-Scn2a (sodium channel, type II, alpha-polypeptide)-D3Arb1-Cat (catalase)-Bdnf (brain-derived neurotropic factor)-D3Arb219-D3Arb2-Sus2 (seminal vesicle secretion II protein)-Sdc4 (ryudocan/syndecan4)-Stn1 (statin-like protein). Eight of these markers were analyzed for polymorphisms in 14 additional inbred rat strains. Three to five alleles were detected for each marker, suggesting that they are highly polymorphic and useful for genetic mapping studies with inbred rat strains. Chromosomal syntenic conservation among rats, mice and humans is also discussed. PMID- 8000135 TI - Phosphoglycerate kinase pseudogenes in the tammar wallaby and other macropodid marsupials. AB - Phosphoglycerate kinase (EC 2.7.2.3; PGK) exists in two forms in marsupials. PGK1 is an X-linked house-keeping enzyme, and PGK2 is a mainly testis-specific enzyme under autosomal control. We have used PGK1 probes derived from two closely related species of macropodid marsupials (kangaroos and wallabies) to demonstrate the existence of a large family of pseudogenes in the tammar wallaby (Macropus eugenii). Over 30 fragments are detectable after Taq digestion. We estimate that there are 25-30 copies per genome. Most are autosomally inherited and are apparently not closely linked. Only two restriction fragments that appeared to be sex linked could be detected. Varying degrees of hybridization of fragments to the probes suggest different levels of homology, and hence different ages of origin. The existence of two PGK1 homologous restriction fragments from the X and a large number from the autosomes was also demonstrated by somatic cell hybridization for two other macropodid species, the wallaroo (M. robustus) and the red kangaroo (M. rufus). These results are compared with those from human and mouse, and it is suggested that the propensity of PGK1 to form pseudogenes is an ancient (approximately 130 MYR BP) characteristic of mammals. The high level of polymorphism detected in the tammar makes these PGK1 probes potentially useful for measuring genetic variability in this species and other macropodids. PMID- 8000137 TI - A genetic map of nine loci on bovine chromosome 2. AB - A male-specific genetic linkage map of nine loci on bovine Chromosome (Chr) 2 (BTA2) was constructed from 306 offspring belonging to six paternal half-sib families. Loci studied were the structural genes for liver/bone/kidney alkaline phosphatase (ALPL). Gardner-Rasheed feline sarcoma (v-fgr) oncogene homolog (FGR), alpha-L-fucosidase 1 (FUCA1), and fibronectin 1 (FN1), and the microsatellite loci ARO28, DU17S2, DU17S3, DU17S4, and DU17S5. Genotyping was performed by restriction fragment length polymorphism (RFLP) for structural genes and polymerase chain reaction (PCR) for the microsatellites. Two genetically independent linkage groups were identified. The order of genes in the first linkage group, L31, is (ARO28-FN1)-FGR-FUCA1-ALPL, covering a map distance of 34.1 cM between terminal markers. The second linkage group, L32, consists of DU17S2-DU17S5-DU17S4-DU17S3 and is 41.3 cM in length. Genetic linkage between FN1 and FGR confirms previous physical assignment of these genes to the same synteny group. Currently, the genetic linkage of FN1 and FGR is unique to cattle and thus localizes a site of chromosomal evolution to a 22-cM interval between the two loci. PMID- 8000138 TI - Genetics of dietary obesity in AKR/J x SWR/J mice: segregation of the trait and identification of a linked locus on chromosome 4. AB - We describe a new multiple gene mouse model of differential sensitivity to dietary obesity that provides a tool for dissecting the genetic basis for body composition and obesity. AKR/J and SWR/J male mice, as well as male progeny of intercrosses between these strains, were fed a high-fat diet for 12 weeks beginning at 5 weeks of age. Body weight and energy intake were assessed weekly. At the conclusion of the dietary manipulation, an adiposity index was calculated by dividing the weight of seven dissected adipose depots by the carcass weight. AKR/J mice had approximately sixfold greater adiposity than SWR/J mice. Examination of the segregation of the adiposity trait in the progeny of crosses between these strains indicates that the trait is determined by a minimum of one to four genetic loci and that there is significant dominance of the AKR/J genotype. A preliminary analysis with markers linked to the known mouse obesity genes ob, db, tub, and fat showed no linkage with these loci. However, a quantitative trait locus was found that maps distal to the db gene on Chromosome (Chr) 4. This locus has been designated dietary obese 1 or Do1. PMID- 8000139 TI - A genetic and physical map of bovine chromosome 11. AB - A genetic map of bovine Chromosome (Chr) 11 (BTA11, synteny group U16) has been constructed from 330 animals belonging to 21 families, which constitute the international bovine reference panel (IBRP). This map is based on 13 polymorphic microsatellite markers, two of which were chosen in previously published maps. Three markers have been isolated from cosmids. Two of the three cosmids have been physically localized by fluorescence in situ hybridization (FISH), to anchor the genetic map on the chromosome. In addition, a biallelic polymorphism in the beta lactoglobulin gene (LGB) has been genetically positioned relative to the microsatellite markers. The most probable order of the markers is: cen-INRA044 BM716-INRA177-(TGLA327, INRA198, INRA131)-INRA111-INRABERN169-(INRA115, INRA032) INRA108-INRABERN162-INRA195-LGB. The total linkage group spans 126 cM, which probably corresponds to most of the chromosome length. The average intermarker distance is about 10.5 cM, allowing the potential detection of a genetic linkage with any Economic Trait Loci (ETL) of this chromosome. Seven of these markers have been previously published by Vaiman and coworkers (1994), two will be published as part of a set of markers (Eggen et al. in preparation), two are described in this paper, and two (BM716, TGLA327) were chosen from the published maps of BTA11 in order to integrate our data with existing maps. All these markers were assigned to synteny group U16 by use of a previously characterized panel of hamster/bovine somatic hybrid cell lines (Guerin et al. 1994).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8000140 TI - Analysis of cDNA sequences from mouse testis. AB - Few mammalian proteins involved in chromosome structure and function during meiosis have been characterized. As an approach to identify such proteins, cDNA clones expressed in mouse testis were analyzed by sequencing and Northern blotting. Various cDNA library screening methods were used to obtain the clones. First, hybridization with cDNA from testis or brain allowed selection of either negative or differentially expressed plaques. Second, positive plaques were identified by screening with polyclonal antisera to prepubertal testis nuclear proteins. Most clones were selected by negative hybridization to correspond to a low abundance class of mRNAs. A PCR-based solid-phase DNA sequencing protocol was used to rapidly obtain 306 single-pass cDNA sequences totaling more than 104 kb. Comparison with nucleic acid and protein databases showed that 56% of the clones have no significant match to any previously identified sequence. Northern blots indicate that many of these novel clones are testis-enriched in their expression. Further evidence that the screening strategies were appropriate is that a high proportion of the clones which do have a match encode testis-enriched or meiosis specific genes, including the mouse homolog of a rat gene that encodes a synaptonemal complex protein. PMID- 8000142 TI - A mouse monochromosome 8 somatic cell hybrid: a reagent for chromosome 8 isolation. PMID- 8000141 TI - A refined restriction map of YAC clones spanning the entire human dystrophin gene. AB - The enormous size of the human dystrophin gene (2300 kb) has so far hindered the analysis of its organization and the characterization at the genomic level of the deletion and duplication mutations causing Duchenne or Becker muscular dystrophy. A detailed physical map of the gene locus would considerably simplify these studies. We constructed a refined, long-range restriction map of the entire human dystrophin gene, using 12 overlapping YAC clones as DNA sources. The sites for six rare cutting enzymes (SfiI, NruI, EagI, BssHII, SacII, and NotI) were mapped by partial digest analysis of YACs over a region of 2600 kb, within a level of resolution of about 10 kb. Such a map provides the first detailed representation of the physical structure of the dystrophin gene. It will be useful for mapping unlocalized exons and, eventually, for the characterization of deletions and duplications leading to disease. PMID- 8000143 TI - Mapping of syntenic groups U7 and U27 to bovine chromosomes 25 and 12, respectively. PMID- 8000144 TI - The genes for endothelin 3, vitamin D 24-hydroxylase, and melanocortin 3 receptor map to distal mouse chromosome 2, in the region of conserved synteny with human chromosome 20. PMID- 8000145 TI - Evaluation of human microdissection clones from the FRAXA region as tools for comparative mapping in the mouse: isolation of a conserved genomic clone close to FMR1. PMID- 8000146 TI - Restriction mapping of yeast artificial chromosomes by UV-mediated partial digestion. PMID- 8000148 TI - Mapping of the gene for rat endothelin-1 (Et1) to chromosome 17. PMID- 8000147 TI - A porcine minisatellite located on chromosome 14q29. PMID- 8000149 TI - Human growth hormone-releasing hormone receptor (GHRHR) maps to a YAC at chromosome 7p15. PMID- 8000151 TI - Marriage of clinical pharmacy and clinical nutrition via computer systems. PMID- 8000150 TI - Mapping vector-adjacent DNA from a 7q human telomeric YAC using RARE. PMID- 8000152 TI - Blood antioxidants and indices of lipid peroxidation in subjects with angina pectoris. AB - We tested the antioxidant hypothesis of coronary heart disease (CHD) by comparing blood antioxidants, indices of lipid peroxidation and classic (CHD) risk factors of 25 subjects with stable angina pectoris with 200 matched controls. Angina subjects had significantly increased plasma concentrations of total cholesterol, low density lipoproteins and triglycerides although body mass index, plasma cotinine concentration and blood pressure were similar to those of the control group. Plasma concentrations of vitamin A, vitamin C and cholesterol- adjusted vitamin E did not differ between the groups although subjects with angina had significantly decreased plasma uric acid concentrations and elevated indices of lipid peroxidation. Although the results are compatible with the antioxidant hypothesis, it is unclear whether the increased oxidative stress in angina sufferers is a cause or consequence of the disease. PMID- 8000153 TI - Metabolic response to a high-lipid, high-nitrogen peripheral intravenous nutrition solution after major upper-gastrointestinal surgery. AB - We compared the metabolic response to peripheral intravenous nutrition (peripheral IVN) with the response to central IVN when given after major gastrointestinal surgery. Eighteen consecutive patients who had undergone upper gastrointestinal surgery were randomly assigned to receive either peripheral IVN (75% nonprotein calories supplied as lipid, n = 9) or central IVN (n = 9). Each group received 0.50 +/- 0.03 g N.kg-1 fat-free mass.day-1 (mean +/- SD with 100:1 kcal:g N (0.42 MJ:1 g N). Metabolic studies were undertaken before IVN (2nd postoperative day) and after 10 days of IVN. Negative nitrogen balance was reversed with both treatments (p < 0.001). The significant net efflux of individual amino acids from peripheral tissue before IVN was reduced toward balance, and there were no significant differences between the groups. The postoperative response of the plasma proteins (fibronectin, prealbumin, and transferrin) was similar in both groups. Peripheral IVN decreased postoperative peripheral net uptake of glucose to a net balance. Central IVN resulted in decreased free fatty acid, glycerol, and beta-hydroxybutyrate concentration with increases in plasma insulin concentration and the net uptake of glucose and pyruvate in peripheral tissue. The effect of intravenous nutrition on the metabolic response to major surgery was similar when nonprotein calories were supplied wholly as glucose requiring a central delivery system or when 75% of nonprotein calories were given as lipid when a peripheral delivery system was used. This study supports the development of peripheral IVN feeding systems. PMID- 8000154 TI - Influence of large intakes of trace elements on recovery after major burns. AB - Because Cu, Se, and Zn are involved in immune and antioxidative defense mechanisms and tissue repair, deficiencies might aggravate complications classically observed with burns. After measuring massive cutaneous trace element losses in 10 burn patients, our aim in this study was to determine whether large intravenous intakes of Cu, Zn, and Se can modify serum trace element levels and recovery after major burns. Ten patients, aged 34 +/- 6 yr (mean +/- SD), admitted to the burns center of a Swiss university hospital with thermal burns on 41 +/- 9% of their body surface were studied prospectively, with trace element balance studies from day 1 (D1) to D7 postinjury. Urine and blood samples were also collected on D10, D15, D20, and D25. The patients were divided into two groups of five and received either standard (group 1, control) or greatly increased (group 2, treatment: 4.5 mg Cu, 190 micrograms Se, and 40 mg Zn/day) trace element intakes. Energy and protein intake and wound treatment were similar in both groups. The treatment group was characterized by improved Cu, Se, and Zn status (increase in serum levels and various protein indicators), a much larger leukocyte increase between D4 and D14 (mainly neutrophils), and shorter hospital stay (45 days) compared with the untreated group (57 days). Grafting requirements were more extensive in group 1. Although severity of injury and wound treatment were similar in the groups, the duration of hospitalization was lower in the treated group. Further studies are required to determine whether this is related to trace element supplementation. PMID- 8000156 TI - Determination of glycerol turnover by stable-isotope technique in humans: a new [1,1,2,3,3-2H5]glycerol derivative for mass-spectrometry analysis. AB - The stable isotope-labeled [1,1,2,3,3-2H5]glycerol analyzed by negative-ion chemical ionization (NCI) mass spectrometry has been proven a valid tracer for studying glycerol kinetics in humans. Because of its high technical complexity, NCI mass spectrometry is available to only a few laboratories. Thus, the aim of our study was to create an alternative method for measuring [1,1,2,3,3 2H5]glycerol enrichment in plasma with a new derivative and positive-ion chemical ionization (PCI) mass spectrometry. It could be demonstrated that the trisacetyl[1,1,2,3,3-2H5]glycerol derivative was able to produce a fragment at m/z = 164 with sufficient intensity. Application of [1,1,2,3,3-2H5]glycerol in seven healthy volunteers resulted in reproducible measurements of basal glycerol turnover rates. The mean glycerol flux rate of 3.02 +/- 0.37 mumol.kg-1 body wt.min-1 after an overnight fast was similar to values reported from studies with comparable protocols. Physiological changes of lipolysis rates after 48 h of fasting followed by infusion of 4 mg.kg-1 body wt.min-1 glucose could also be adequately studied in one subject. Fast-induced elevated glycerol turnover at 7.56 mumol.kg-1 body wt.min-1, was substantially suppressed to 1.13 mumol.kg-1 body wt.min-1, when glucose was administered. The easily performed trisacetyl[1,1,2,3,3-2H5]glycerol derivative analyzed by PCI mass spectrometry is suitable for studying glycerol kinetics in humans. PMID- 8000158 TI - Diet assessment: can it change attitude and behavior? PMID- 8000155 TI - Albumin catabolic rate and protein-energy depletion. AB - Severe malnutrition was induced in New Zealand White rabbits by restricting dietary nitrogen and energy to 9.1 and 57.4% of normal intake, respectively. Albumin distribution and metabolism were then determined in these and in control animals. The fractional catabolic rate was reduced by 33.7% in the depleted animals, but there were no changes in the other distribution rate constants. In particular, we were unable to demonstrate a significant change in the relative distribution of albumin between the intravascular and extravascular spaces. In addition, albumin concentration in the depleted group only fell toward the end of the experiment. We conclude that, with acute severe malnutrition, plasma albumin concentration is maintained until late and is therefore not a good nutritional marker. Also, maintenance of intravascular albumin concentration is not at the expense of extravascular albumin. PMID- 8000157 TI - Nutritional support in patients with alpha,beta-lipoproteinemia. PMID- 8000159 TI - Clinton health care reform ... affecting the process. PMID- 8000160 TI - New restrictions on health claims for dietary supplements. PMID- 8000161 TI - Strategies for reducing dietary risk factors: the high risk individual versus population-wide interventions. PMID- 8000162 TI - Hunger disease. Studies by the Jewish physicians in the Warsaw ghetto. 1979. PMID- 8000163 TI - [Prevention and health promotion as a responsibility of legal health insurance- exemplified by a local insurance bureau]. AB - The German statutory health insurance bodies are legally obliged to support health promotion of the assured, as stipulated by German social legislation since 1988. An analysis was performed covering a period of 5 years (1986-1990) in respect of all health-promoting and preventive measures carried out by a local so called "Allgemeine Ortskrankenkasse (= AOK)" looking after 170,000 insured persons, to find out the impact of the new legislation on the practice of that particular local insurance body. During the period under report no changes in activities were recorded that would be worth mentioning. Although expenditure for prevention rose by 50%, it was nevertheless impossible to administer preventive measures to all the insured persons throughout the area since the total amount reserved for this purpose was only 0.42% of the overall expenditure. A major portion of the documented measures such as consultation on foods, health promoting sports, getting rid of the smoking habit, social counselling, anti stress training courses and the like were not performed for primary prevention but on subjects who were already sick (diabetics, cardiovascular patients, patients suffering from diseases of the locomotor apparatus). Definite statements on the quality or success of the measures were possible in selected cases only. The results of the study prompted organisational improvements in that particular insurance body. Since their financial resources are limited, these bodies should shift the emphasis of their expert possibilities in prevention to on-target care of high-risk groups and to the training of multiplicators. PMID- 8000164 TI - [Quality assurance in sociomedical decision processes exemplified by documentation of occupational anamnesis in final sociomedical expert assessment]. AB - 426 German sociomedical expertises written by sociomedical specialists appointed by various German statutory insurance bodies were examined (compulsory pension fund, medical services of statutory health insurance, medical officers of the German government-controlled labour offices and experts appointed by various rehabilitation centres). A wide gap was found between reality on the one hand--as represented by the patient's previous work and the conditions prevailing at his particular place of work and on the labour market in general--and the theoretical postulates set by the doctor on the other hand. These deficits are defined in the present article and concrete suggestions are made on overcoming them. The problems pinpointed by this pilot study are intended to stimulate a development project to standardise patient anamnesis in relation to the type and place of work, irrespective of the various statutory health insurance bodies involved. PMID- 8000165 TI - [The contribution of social work to psychosomatic rehabilitation in social insurance]. AB - Psychosomatic rehabilitation conducted by the social insurance system aims at improvement or restitution of the patient's impaired competence of leading a regular social life and in particular of taking part in the working process. Psychoanalytically based in-patient psychotherapy is focussed on the patient's psychosocial conflict constellations and tries to enable him to cope with his daily social tasks in a satisfying and self-reliant way. In the process of psychosomatic treatment the social worker has an important function in the comprehensive treatment plan due to his expert knowledge and counselling competence. In coordination with the treatment team the social worker makes a genuine contribution in examining and diagnosing the patient, motivating him/her, working out a treatment scheme, realising the treatment process, completing the treatment and arranging for further social and psychotherapeutic care. PMID- 8000166 TI - [The adolescent psychiatric service in the Saxony free state and its contribution to health promotion]. AB - The tasks of the Public Health Service with particular reference to children and teenagers in the German Federal Land of Saxonia are laid down by legislation enacted by the Ministry for Culture on health care in schools (30.7.92). It is the main task of health promotion in schools to prevent health disorders and disturbed development in children and teens. The following tasks must be performed, among others: medical examination before admittance to school and in the classes 2, 5 and 9; public hours of consultation; and statistical documentation. All the essential demands on modern public health service for children and teens are part of current legislation in Saxonia. PMID- 8000167 TI - [Mumps--occupational exposure and aspects of epidemiologic susceptibility]. AB - 1041 persons working in the university hospital of Freiburg, Germany, were tested for mumps antibodies. The first part of the investigation was conducted between 1986 and 1988, the second one in 1992. Significant decrease in seroprevalence between study I (67% immune) and study II (63% immune) was found. Average immunity of paediatric nurses was significantly higher (76%) than that of non exposed persons (59.7%). 195 persons were vaccinated (live vaccine) and 84.6% seroconverted. PMID- 8000168 TI - [Vaccination recommendations of the current vaccination committee of the Federal Health Service 22 February 1994]. PMID- 8000169 TI - [AIDS--comparison of knowledge, attitude and behavior of Hannover and Leipzig medical students]. AB - An investigation was carried out in students of the faculties of medicine at Hannover and Leipzig by handling a questionnaire on their knowledge, beliefs and attitudes on AIDS. The sample was 354 at Hannover and 365 at Leipzig consisting of students at the beginning of the first course on the one hand and at the end of studies on the other, both in 1990/91. In the two cities an acceptable knowledge was found of the basic generals of HIV-transmission. Differences appeared at the estimation on behalf of infection-risks by non detectable transmission ways. There is no worth mentioning difference in the students' knowledge between the first and the fifth academic year. On the contrary, uncertainties are stronger marked at the end of the courses than in the beginning. Students' attitudes are very similar in Hannover and Leipzig. Significant differences between Hannover and Leipzig are demonstrable especially on beliefs. Medical students in Leipzig tend sooner to be in favour for interventional measures by the public authorities, clearly visible by their advocating a wide use of HIV-test application to patients, clinic staff and other health professionals even against their will. The students in Hannover are more liberal in this point. Altogether the comparison between Hannover and Leipzig shows a lot of equalities. Existing differences may be on the way to disappear within the farther process of German unification. PMID- 8000171 TI - [New responsibilities via the health care structural law concerning inpatient treatment]. AB - The new Health Care Structural Law (GSG) brings about changes in e.g. medical care in hospitals, the consequences of which are of utmost significance. New forms of payment challenge hospitals to take into account in the hospital management the various forms of payment, to define new programmes of hospital performance and the realise competitive aspects while maintaining the quality of medical care. For the first time ever the new system of nursing fees focuses on the performance of the hospital instead of on its costs. The GSG induces a need to act in various areas of medical care in hospitals: The nursing staff regulation and the psychiatry staff ordinance require a procedure that leads to feasible results in contract negotiations, planning decisions and budget negotiations. In the model project in accordance with section 275a SGB V the necessity of the stay in hospital will be examined to verify that ambulant medical care takes precedence over medical care in hospital. The implementation of section 301 SGB V "Hospitals" is to guarantee a correct accounting with hospitals and is intended to enable the statutory health insurance institutions to perform their task as established by law to examine the necessity and duration of patient's stay in hospital. The evaluation and implementation of these tasks require solutions that do not focus on the individual case but lead to a systematic approach. Future examination procedures have to take the local conditions into account. The contents of the examinations must be standardised to facilitate a comparison on a regional and national level. PMID- 8000172 TI - [Professional congress by invitation of the Public Health Service of the Bavarian State Ministry for Vocational and Social Regulation, Families, Women and Public Health on the topic "Scientific principles in public health service"]. PMID- 8000170 TI - [Dioxin level of small volume gardeners in Duisburg]. AB - The PCDD/F levels were determined in the venous blood of 21 allotment gardeners in Duisburg (Germany). Soil analyses had shown elevated levels of PCDD/F in garden soil (range 16.4-77.6 ng I-TE/kg). Vegetable plants also had elevated levels of PCDD/F, mainly due to airborne contamination. The highest levels were found in kale (2.6-65.6 ng I-TE/kg d.w.) and endive (1.7-28.5 ng I-TE/kg d. w.). The study population consisted of 5 females and 16 males (mean age 57 years; range 43-67 years), who had been cultivating their allotment gardens for an average of 20 years (range 7-36 years). About 50% of their total vegetable consumption and 30% of their fruit consumption were from their own gardens. The mean 2.3.7.8-TCDD toxicity equivalents (TE) of PCDD/F in blood fat were 44.3 pg I TE/g fat (range 29.2-81.1 pg I-TE/g fat). Compared to reference data these values are within the range of background PCDD/F-levels in the German population. The concentrations in individual gardeners as well as the congener pattern were not different from those of normal subjects. The present study shows that increased levels of PCDD/F in garden soil and garden products do not have a significant effect on the PCDD/F burden in gardeners, even if they consume homegrown vegetables and fruits from their own allotment gardens for many years in succession. PMID- 8000173 TI - Fluorescent tracer and pesticide penetration through selected protective clothing. PMID- 8000175 TI - Droplet size characterization of three aerial malathion spray programs. PMID- 8000174 TI - Survey of pesticide use by Ontario greenhouse chrysanthemum producers. PMID- 8000176 TI - Organochlorine pesticide contaminants in human adipose tissue collected in Ankara (Turkey) 1991-1992. PMID- 8000178 TI - Trace metal contamination study on scalp hair of occupationally exposed workers. PMID- 8000179 TI - HCB levels in Spanish sterilized milk. PMID- 8000177 TI - Total and metallothionein-bound cadmium in the liver and the kidney of a population in Barcelona (Spain). PMID- 8000180 TI - Transfer experiment study on two winter annuals around a coal-fired power plant. PMID- 8000181 TI - Degradation of chloroneb, triadimefon, and vinclozolin in soil, thatch, and grass clippings. PMID- 8000182 TI - Residues of glyphosate and its principle metabolite in certain cereals, oilseeds, and pulses grown in Canada, 1990-1992. PMID- 8000183 TI - PCB congeners in tissues of European otter (Lutra lutra). PMID- 8000184 TI - Ground-spray treatment with deltamethrin against tsetse flies in NW Zimbabwe has little short term effect on lizards. PMID- 8000185 TI - Effect of the bioflavonoid morin on HEp-2 cells. PMID- 8000186 TI - Interactive effects of cadmium and retinoic acid on mouse limb bud development in vitro. PMID- 8000187 TI - Effect of synthetic humic acid-multimetal complex on human plasma prothrombin time. PMID- 8000188 TI - Multiple dose toxicokinetic influence on the estrogenicity of 2,2',4,4',5,5' hexachlorobiphenyl. PMID- 8000190 TI - Accelerated rates of organolead transformation following nutrient enrichment of contaminated ground water. PMID- 8000189 TI - Influence of cadmium on ketamine-induced anesthesia and brain microsomal Na+, K(+)-ATPase in mice. PMID- 8000191 TI - Accumulation and toxicity of iron and manganese in Spirodela polyrrhiza (L.) Schleiden. PMID- 8000192 TI - Hydrocarbons in seawater and sediment from the west coast of Peninsular Malaysia. PMID- 8000193 TI - Acute toxicity of technical trichlorphon to cyprinid fish. PMID- 8000194 TI - The past is prologue.... PMID- 8000195 TI - Goldie Allen: Appalachian itinerant Red Cross nurse. PMID- 8000196 TI - What's up with the new volatile anesthetics, desflurane and sevoflurane, for neurosurgical patients? PMID- 8000197 TI - Evaluation of a 7.5 French pulmonary catheter for continuous monitoring of cerebral venous oxygen saturation. AB - We studied a 7.5 French Opticat fiberoptic catheter/Oximetrix computer system as a tool for continuous monitoring of oxygen saturation of jugular venous blood. Eight healthy volunteers had a catheter placed with the tip in the bulb of the right internal jugular vein. During baseline condition, hyperventilation, and rebreathing, jugular venous oxygen saturations ranging from 35 to 85% were obtained. Simultaneous with drawing a blood sample, the value obtained with the fiberoptic catheter was recorded. The oxygen saturation of the blood sample was analyzed in vitro using a bench oximeter. A total of 150 paired values was obtained. In 15 of these cases, the computer indicated that the intensity of the reflected light was insufficient. A difference of > 12% oxygen saturation between the paired values was obtained for all of these pairs. The regression coefficient for the remaining 135 data pairs was 0.95, the mean difference was -0.54%, and the limits of agreement were -9.5 to 8.4%. We conclude that the 7.5 French Opticat catheter is useful if values obtained during improper light intensity are excluded. PMID- 8000198 TI - CSF, sagittal sinus, and jugular venous pressures during desflurane or isoflurane anesthesia in dogs. AB - Previous studies to determine whether desflurane increases cerebrospinal fluid (CSF) pressure are inconclusive because none have included all of the following: multiple doses of desflurane, administration for at least several hours, examination at normo- and hypocapnia, a concurrent comparison group, direct measurement of both intra- and extracranial CSF pressures, and measurement of venous pressures that influence CSF pressure. The present study was designed to determine whether CSF pressure increases during 4.0 h desflurane anesthesia using a study design that included the above elements. Catheters were placed in the lateral cerebral ventricle, cisterna magna, sagittal sinus, and jugular vein of 12 dogs anesthetized with thiopental 12 mg.kg-1.h-1 and halothane 0.5 to 0.8%. Catheter pressures were measured, and the CSF-sagittal sinus pressure gradient and slope of the gradient to CSF pressure relationship were determined during control conditions. Then, 6 dogs were anesthetized with desflurane and 6 dogs were anesthetized with isoflurane, and the same values were determined for 1.0 h at each of four experimental conditions: 0.5 and 1.0 minimum alveolar concentration (MAC) during normocapnia (PaCO2 35-39 mm Hg) and 0.5 and 1.0 MAC during hypocapnia (PaCO2 20-24 mm Hg). CSF and sagittal sinus pressures, but not jugular venous pressure, increased with both desflurane and isoflurane. The greater increase of CSF pressure with 4.0 h desflurane (to 40.2 +/- 12.7 cm H2O) than with 4.0 h isoflurane (to 26.2 +/- 11.5 cm H2O) was attributable to an increase of CSF pressure that was greater during 2.0 h desflurane and normocapnia than during 2.0 h isoflurane and normocapnia, and to an increase of CSF pressure during 2.0 h desflurane and hypocapnia that was similar to that during 2.0 h isoflurane and hypocapnia. The greater increase of CSF pressure during desflurane may have resulted, in part, from increased CSF volume as indicated by a positive CSF-sagittal sinus pressure gradient (in contrast, there was little or no CSF sagittal sinus pressure gradient during isoflurane) and a steeper slope of the gradient to CSF pressure relationship. PMID- 8000199 TI - Propofol prevents or elevates the threshold for lidocaine-induced seizures in rats. AB - Hypothesizing that propofol's pro and anticonvulsant effects might be dose dependent, we determined the effect of 25, 50, and 100% of a previously determined anesthetic dose of propofol for rats on the amount of lidocaine required to induce seizures. Lidocaine was infused at 2.5 mg kg-1 min-1 into animals that were receiving either (a) 70% N2O balance O2 (n = 10), control group, (b) 2 mg kg-1 bolus followed by 12 mg kg-1 h-1 propofol infusion with 70% N2O (n = 10), group 2, (c) 4 mg kg-1 followed by 24 mg kg-1 h-1 propofol with 70% N2O (n = 20), group 3, (d) 8 mg kg-1 followed by 48 mg kg-1 h-1 propofol with 70% N2O (n = 10), group 4, or (e) 8 mg kg-1 followed by 48 mg kg-1 h-1 propofol without N2O (n = 10), group 5. Temperature PaCO2, and pH were maintained within normal limits until disturbed by seizure activity or lidocaine toxicity. The plasma concentration of lidocaine required to induce electroencephalographically (EEG) detected seizures was 8.7 +/- 0.7 micrograms ml-1 in control animals, 16 +/ 1.7 micrograms ml-1 in group 2, and 32 +/- 4 micrograms ml-1 in 13 animals from group 3 that experienced a seizure (p < 0.01). Seizures did not occur in seven of 20 group 3 rats.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8000200 TI - Sevoflurane versus halothane anesthesia after acute cryogenic brain injury in rabbits: relationship between arterial and intracranial pressure. AB - The relationship between intracranial pressure and arterial blood pressure during sevoflurane or halothane anesthesia was evaluated in New Zealand white rabbits after cryogenic brain injury. Fourteen rabbits were randomized to be anesthetized with 1.5 MAC of sevoflurane or halothane in oxygen. All animals were paralyzed with pancuronium, and mechanically ventilated. A cryogenic lesion was created over the left hemisphere. Thirty minutes later, the intracranial pressure had risen to a mean value of 15 mm Hg. The inhaled concentration of anesthetic drugs was then increased to achieve a blood pressure of 35 mm Hg. Baseline measurements were made of monitored variables including mean arterial pressure, intracranial pressure, esophageal temperature, end-tidal CO2, and arterial blood gases. Neosynephrine was then infused to raise the blood pressure from 35 to 100 mm Hg during 20 min. The PaCO2 was maintained between 38 and 42 mm Hg. At baseline, there were no significant differences in mean arterial pressure, intracranial pressure, and blood gas values between the two groups. The intracranial pressure in the sevoflurane anesthesia group increased from 11 +/- 1 to 44 +/- 4 mm Hg as mean arterial pressure increased from 35 to 100 mm Hg. Intracranial pressure in the halothane anesthesia group increased from 9 +/- 1 to 32 +/- 3 mm Hg during the same range of blood pressure. Linear regressions of intracranial pressure on mean arterial pressure were performed for each of the two anesthetic groups. The slope of the regression line for the sevoflurane animals (0.491) was significantly greater than that for the halothane animals (0.323, p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8000201 TI - Neuronal protection by intraischemic brain perfusion: an electron microscopy study in the rat. AB - Organ perfusion with bloodless solutions is an established clinical method for protecting the heart against ischemic damage. In our study, we evaluated the effects of intraischemic bloodless brain perfusion on postischemic ultrastructural neuronal changes in a model of severe incomplete forebrain ischemia produced by hemorrhagic hypotension combined with temporary carotid occlusion in the rat. Four groups of rats were compared. During an ischemic insult of 30 min, the brains of two groups were perfused via both external carotids with either a normosmolar normothermic magnesium-enriched perfusate (MgSO4, 30 mM; NaCl, 37 mM; mannitol, 180 mM; n = 10) or a normothermic normal saline solution (n = 9) at a rate of 6 ml/h. Two other groups (ischemia without perfusion, n = 8; no ischemia and no perfusion, n = 7) served as controls. After 30 min of ischemia, withdrawn blood for hemorrhagic hypotension was reinfused, the carotid arteries reopened, and the brains reperfused for 2 h. After perfusion fixation, qualitative and quantitative evaluation of postischemic cell changes of hippocampal CA1 neurons was performed by electron microscopy. Brain perfusion with the magnesium-containing solution significantly protected neurons against ischemic cell changes and provided an ultrastructural pattern similar to that seen in the nonischemic control group. In contrast, brain perfusion with normal saline solution did not result in neuronal protection. We conclude that intraischemic intracarotid brain perfusion with magnesium-enriched perfusate protects hippocampal neurons significantly against ischemic cell changes in the early reperfusion period after transient severe forebrain ischemia. PMID- 8000202 TI - MAC of xenon and halothane in rhesus monkeys. AB - Local cerebral blood flow (LCBF) maps produced by 33% xenon-enhanced computed tomographic scanning (Xe/CT LCBF) are useful in the clinical diagnosis and management of patients with cerebrovascular disorders. However, observations in humans that 25-35% xenon (Xe) inhalation increases cerebral blood flow (CBF) have raised concerns that Xe/CT LCBF measurements may be inaccurate and that Xe inhalation may be hazardous in patients with decreased intracranial compliance. In contrast, 33% Xe does not increase CBF in rhesus monkeys. To determine whether this interspecies difference in the effect of Xe on CBF correlates with an interspecies difference in the anesthetic potency of Xe, we measured the minimum alveolar concentration (MAC) of Xe preventing movement to a tail-clamp stimulus in rhesus monkeys. Using a standard protocol for the determination of MAC in animals, we first measured the MAC of halothane (n = 5), and then used a combination of halothane and Xe to measure the MAC of Xe (n = 7). The halothane MAC was 0.99 +/- 0.12% (M +/- SD), and the Xe MAC was 98 +/- 15%. These results suggest that the MAC of Xe in rhesus monkeys is higher than the reported human Xe MAC value of 71%. Thus the absence of an effect of 33% Xe on CBF in the rhesus monkey may be related to its lower anesthetic potency. PMID- 8000203 TI - Effect of the Valsalva maneuver on intracranial hypertension. AB - We describe a case of intracranial hypertension in a previously healthy 25-year old man who sustained a head injury in a motor vehicle accident, in whom a Valsalva maneuver resulted in parallel reductions in mean arterial blood pressure, cerebral blood flow velocity in the middle cerebral artery, and intracranial pressure. The effects of raising intrathoracic pressure in patients with intracranial hypertension are discussed. PMID- 8000205 TI - Inhalational versus total intravenous anesthesia for neurosurgery: theory guides, outcome decides. PMID- 8000204 TI - Total intravenous anesthesia is best for neurological surgery. AB - We believe that today balanced TIVA represents the best anesthetic technique for neurological surgery. Freely acknowledging that this point of view is unproven (36) with regard to the hard criterion of patient outcome on leaving the hospital, we submit that the intermediate or surrogate criteria discussed make a convincing case for preferring TIVA to volatile-based anesthetic techniques. Until a study demonstrating hard outcome differences between the two techniques is achieved, we will continue to encourage the use of TIVA in neuroanesthesia, based on its practical (anesthetic depth, neuromonitoring, surgical field) and theoretical (homeostasis, metabolism, antinociception, neuroprotection) advantages. PMID- 8000206 TI - Intraoperative "pseudoseizure" caused by a faulty electrically controlled operating table. PMID- 8000207 TI - The January bushfires: gone but not forgotten. PMID- 8000208 TI - The routine of post anaesthetic observations. AB - Fifty registered nurses were interviewed to determine how nurses view routine post anaesthetic observations (RPAOs). A structured interview established whether nurses routinely carry out post anaesthetic observations and if they believe that routine observations are part of ward procedure or hospital policy. Nurses' beliefs about the necessity for performing these observations and the rationales they use to justify them were also explored. The results show that all the nurses sampled interpreted RPAOs to mean half hourly vital sign measurements for four hours, and believed that the regimen was prescribed by ward or hospital policy. Many believed that this frequency was necessary to detect complications of surgery or anaesthesia. A small number of nurses felt obliged to comply with perceived hospital policy despite an assessment that it was unnecessary. Procedure-driven assessment and tradition rather than individualized patient assessment appear to be directing post operative nursing actions. PMID- 8000209 TI - Been there, done that? Consciousness raising, critical theory and nurses. AB - The concept of consciousness raising has become somewhat tired and jaded in nursing literature. Indeed the notion of consciousness raising and its associated catchcry of 'making the personal political', is almost so hackneyed as to be somewhat unfashionable and cliched in the 1990s. This is due, at least in part, to the fact that consciousness raising emanated from the women's movement of the 1960s and was originally directed at linking the personal and the political, but in nursing emphasis has often been given to the personal with little recourse to the political. It is thus timely and important to draw on insights afforded by critical perspectives and synthesize them anew with the tenets of consciousness raising in order to make explicit the power relations and structural oppression implicit in the nursing context. If consciousness raising, and the making of the personal political, are combined with the theoretical insights provided by critical theorists such as Faoucault (1977, 1980), it is possible to re-orient and re-energise the somewhat trite and worn catchcry of the personal as political. PMID- 8000210 TI - Nurses' assessment of pain intensity and choice of analgesic dose. AB - Under-treatment of all types of pain has been identified in many countries throughout the world. For example, the World Health Organization states that unrelieved cancer pain is an international problem. Lack of education of health care professionals, including nurses, is frequently cited as a major reason for under-treatment of pain. This survey of 517 Australian nurses suggests that they have some of the same educational needs as nurses in North America, such as how to assess pain intensity and how to select a dose of an opioid analgesic that is appropriate for the individual patient. PMID- 8000211 TI - Misery and myth: a connection between society and inadequate pain control? AB - Despite numerous studies and re-education strategies spanning two decades, inadequate relief of pain remains a significant problem for both clients and nurses. This paper explores the literature on the extent of the problem and suggests that societal attitudes about narcotic drugs are a major contributing factor to this problem. Encouraging reflective practice is one of the strategies suggested to address the situation. PMID- 8000212 TI - Nursing knowledge: myth or reality? PMID- 8000213 TI - Clinicians, please educate diabetic clients. PMID- 8000214 TI - Action research and action researchers: some introductory considerations. AB - Action research has become increasingly acceptable as a legitimate methodology with which to research nursing; the term 'action research', however, now covers a range of approaches to strategic intervention and action theory generation. The reasons behind the 'rise' of action research, the differing approaches the term covers and the common characteristics of these approaches are described and their implications for action researchers discussed. The nature of the action theories that action research aims to surface/generate and validate is also discussed. PMID- 8000215 TI - Lessons from a dying client. PMID- 8000216 TI - Night shift in ICU. PMID- 8000217 TI - [Develop cause of integrated traditional and Western medicine to greet coming of 21 century (2)]. PMID- 8000218 TI - [Clinical study on prevention and treatment to chemotherapy caused nephrotoxicity with jian-pi yi-qi li-shui Decoction]. AB - 95 cases of cancer patients were treated with large dose of Cisplatinum. They were randomly divided into treated group with Chinese medicinal herbs (49 cases) and control group with hydration treatment (46 cases). Multiple indexes were selected to observe effect on renal function. The result showed that the level of blood urea nitrogen (BUN), creatnine (Cr), beta 2 microglobulin (beta 2-MG), urea N-acetyl-beta-glucosaminidase (NAG) of treated group lowered. After treatment the difference of BUN, Cr between the two groups was significant (P < 0.05). It suggested that Jian-Pi Yi-Qi Li-Shui Decoction (JPYQLSD) was superior to hydration group in preventing the large dose of Cisplatinum induced nephrotoxicity. It was also used to treat 44 cases-times of chemotherapy caused renal failure. The total effect rate is 93.18%. The difference of the level of BUN, Cr between before and after treatment was very significant (P < 0.01). It is proved that JPYQLSD has good effect in treating chemotherapy caused renal failure. PMID- 8000219 TI - [Relationship between T cell subsets and traditional Chinese medicine type in patient with ovarian tumor]. AB - In order to study the difference in TCM types as well as between Deficiency and Excess type in immunity in the patients with ovarian tumors, the profile of peripheral blood T lymphocyte subsets in 73 cases of ovarian tumors was determined by using flow cytometry and monoclonal antibody technique. The results showed that the total T cells (OKT3) of peripheral blood were almost normal in 73 tumor cases. And 50 of them were malignant tumors in which T helper cell were progressively decreased and T suppressor cell gradually increased in accordance with the order of Qi-Deficiency, Yin-Deficiency, Qi-Yin Deficiency types. The T4/T8 ratio showed significant difference (P < 0.01) compared with the control group and the initial ovarian tumor group. These results indicated that the change in the T lymphocyte subset in tumor was correlated with TCM type and this serves as both clinically sensitive indexes of different TCM type and reflection of the patient's immunologic status. PMID- 8000220 TI - [Clinical study of the treatment of endometriosis with traditional Chinese medicine]. AB - 46 endometriotic patients were treated by the method of removing Blood Stasis and resolving Phlegm, softening and resolving the Lump (RBS-RP-SRL). The total effective rate was 91.3%. Among them, the effective rate of dysmenorrhea was 97.6%, that of anal tenesmic was 94.3%, that of intercourse pain 86.7%, and 86.7% diminished in size of mass or nodule, 6 of 10 infertility patients became pregnant. It was showed by the laboratory assay that the cases were in the abnormal condition of nail bed microcirculation and hemorheology, which could be significantly improved after treatment. The results revealed that it was effective in treating endometriosis with the method of RBS-RP-SRL. PMID- 8000221 TI - [Prevention and treatment of intrauterine device caused abnormal menstruation by huan-an powder]. AB - Huan-an Powder (HA) was used to prevent and treat the intrauterine device (IUD) caused abnormal menstruation in 155 cases, who were divided into the prevention group and treatment group. In the former, 70 cases had taken the powder, resulting in no obvious difference in their amounts of menstrual blood, menstrual period, menstrual cycle and hemoglobin between after and before the applying of IUD (P > 0.05). In the latter, there were 85 cases, of whom, 30 with hypermenorrhea, 30 with menostaxis, and 25 with preceded menstrual cycle, the total effective rate was 90%, 93% and 88% respectively. After HA was used, the amount of the menstrual blood was significantly reduced, the menstrual period markedly shortened (P < 0.01), while the menstrual cycle was prolonged and hemoglobin increased significantly (P < 0.01). The results showed that HA is a good recipe in preventing and treating abnormal menstruation caused by applying IUD, with highly effective and safe, and without any side effects and contraindications. PMID- 8000222 TI - [Therapy of integrated traditional Chinese medicine and Western medicine on 74 lupus nephritis]. AB - The therapy of integrated traditional Chinese medicine and Western medicine (TCM WM) on lupus nephritis (LN) was explored. There were 74 and 66 cases in the TCM WM group and WM group respectively. The results showed that in TCM-WM group the effective rate and recurrence rate were 95.9% and 4.1% respectively, while in WM group they were 80.3% and 21.2% respectively. The occurrence rate of side effect was 37.9% and 77.3% in TCM-WM group and WM group respectively. It indicated that the therapy of TCM-WM could significantly enhance curative rate and reduce recurrence and side effect rate. PMID- 8000223 TI - [Gastric motility in patients with spleen-deficiency symptoms]. AB - By using a method for synchronously-detecting gastric myoelectric activity and intraluminal pressure and a radioimmunoassay of plasmic motilin, gastric motility, plasmic level of motilin and their relationship in 12 normal individuals and in the patients with a variety of Spleen-Deficiency (SD) Syndromes, i.e. 12 SD with Cold type (H type), 7 SD with Stomach-Yin-Deficiency type(I type), 38 SD with Heat type (R type) and 6 SD with Liver-Qi-Stagnation type (U Type) were investigated. The results showed: degree of myoelectric dysrhythmia and rate of electro-mechanical decouple in all patients (except for I type) were much higher than those in the normals (P < 0.01 or P < 0.05); both mean frequency and amplitude of contraction in the patients were decreased; percentage of contractive action in the patients (except for I type) was lower than that in the normals (P < 0.05); plasmic level of motilin in the patients (except for I type) had a tendency to increase and had a linear correlation to degree of myoelectric dysrhythmia (r = 0.33, P < 0.01). It was suggested that some significant disorders of gastric motility exist in different SD patients and there might be an intrinsic cause effect relationship among increased plasmic motilin, myoelectric dysrhythmia and abnormal mechanical motion. The similar changes suggested that there is pathophysiological mechanism of SD syndrome. Furthermore, this synchronously-detecting method was useful to discover intrinsic relationship between gastric myoelectric activity and mechanical motion. PMID- 8000224 TI - [Traditional Chinese medicine and Western medicine treatment for severe intractable head injury]. AB - 38 cases of severe intractable head injuries were treated by TCM-WM treatment, the survival rate was 68.4%, which was difficult or ineffective for Western medicine treatment. The author lay emphasis on taking the following measures: (1) Place nasal feeding tube in the nose as early as possible; (2) Take Zenye Tang and Shengmai Yin as chief prescription for nourishing Yin and replenishing Qi; (3) Take large dose of citicoline, Angong Niuhuang Wan and Xuefu Zhuyu Tang to promote resuscitation; (4) When pulmonary infection was serious and antibiotic ineffective, Shashen Maidong Tang and Ditan Tang etc. could be used. PMID- 8000225 TI - [Effects of gossypol acetate, danazol, progesterone and GnRH-A on estrogen and progesterone receptors of human endometrial cells]. AB - In order to evaluate the drugs in treating endometriosis, the direct effects of gossypol acetate, danazol, progesterone, and gonadotropin releasing hormone agonist (GnRH-A) on the isolated human endometrial cells were determined by DCC assay. The binding capacity of cytosolic estradiol receptor (E2R) and progesterone receptor (PR) in groups treated with gossypol acetate or progesterone decreased. In danazol-treated group, the binding capacity of PR decreased but not that of E2R. GnRH-A showed no significant effect on the binding capacity of E2R and PR. There was a significant linear correlation between the inhibitory rates of PR binding capacity of progesterone and danazol. The results suggested that gossypol acetate, danazol and progesterone might have peripheral effects mediated by steroid receptors, while GnRH-A work clinically through the central path way only. PMID- 8000226 TI - [Effect of anti-aging drug on the activity of DNA methylase in rat liver]. AB - An obvious anti-aging effect was found by Bushen Shengxue drug to treat Wistar rats. Using a method about incorporation of 3H-labeled methyl group of S-adenosyl methionine (SAM) into DNA bases, the DNA methylase activity was assayed. The specific activity of DNA methylase was increased by treatment of this drug. The chromatographic behaviour of DNA methylase from rat liver was also changed. These results showed that the mechanism of anti-aging effect of this drug is probably related to DNA methylation. PMID- 8000228 TI - [Experimental study on huogu granule in treating aseptic necrosis of femur head]. AB - The pharmacological activities and acute toxicological activities of Huogu Granule (HGG) on the basis of clinical treatment of aseptic necrosis of head of femur were studied. It was observed that medium and high dose of HGG could reduce the inflammatory reaction, inhibit the enhancement of the capillary permeability and decrease the frequency of body twisting obviously in mice. All of these were significantly better than that of normal saline control group (P < 0.05, P < 0.01). It showed that HGG had a noticeable anti-inflammatory and analgesic effect. Also HGG was found to improve the absorption of serum Ca, P and the development of femoral growth in chicken embryo. LD50 could not be determined in acute toxicity test, although the dose of 50g/kg.24hr was about 166.7 times of the dosage used for human adult clinically. It demonstrated that the acute toxicity of HGG is negligible. PMID- 8000227 TI - [Histological study on repairing experimental pulp chamber floor perforations with yunnan bai-yao in dog]. AB - Yunnan Baiyao (YNBY), amalgam, hydroxylapatite and calcium hydroxide were used separately in repairing the experimental pulp chamber floor perforation (PCFP) of dog teeth. The animals were killed at the time of 1, 4, 8 and 12 weeks after experiment. The experimental teeth with periapical tissue were removed and observed their histological changes by optical microscope. The effects that different materials in repairing the tissue of PCFP were observed. Twenty teeth were taken from every dog, each group contained four teeth, the others were used for control group. RESULTS: In initial period (1st, 4th week) inflammatory infiltration was present in PCFP of every group, but the group with YNBY was milder. Pyogenic foci were present in the hydroxylapatite and calcium hydroxide groups. In late stage of experiment (8th and 12th week) inflammatory reactions of each group were alleviated except control group. Epithelial metaplasia and cicatritation were found in the vicinity of perforated area. Dentin cementum and alveolar bone were absorbed in majority of experimental group. It was also observed in the group with YNBY. But in late stage similar cementum formation and alveolar bone neogenesis were found in the perforated area around the repairing materials. It revealed that hemostasis, Promoting Blood Circulation to Remove Stasis and antiphlogistic actions were advantageous to the inflammation, control and repair course of the PCFP. The article discussed that YNBY might promote the repairing of cementum and alveolar bone of perforated area. PMID- 8000229 TI - [A survey of clinical application of method for reinforcing kidney and activating blood]. PMID- 8000230 TI - [Progress on study of anaphylactic purpura treated with traditional Chinese medicine and Chinese materia medica]. PMID- 8000232 TI - Humoral immunological parameters in Italian patients with oral lichen planus. AB - Serum humoral immunological parameters were determined in 25 patients with atrophic-erosive forms of oral lichen planus (OLP) (Group 1), in 28 patients with reticular-plaque-like lesions of OLP (Group 2) and in 21 healthy patients without oral lesions (Group 3). Comparing patients affected by atrophic-erosive forms of OLP (Group 1) with normal controls (Group 3), increased levels of serum IgG approaching the statistical significance were found (Kruskal-Wallis test p = 0.0572). It was also found a significantly higher value of kappa (Kruskal-Wallis test p = 0.0017; Mann-Whitney test with Bonferroni's correction p < 0.001) and lambda (Kruskal-Wallis test p = 0.0346; Mann-Whitney test with Bonferroni's correction p = 0.013) light chains in patients with atrophic-erosive OLP (Group 1) as compared with normal controls (Group 3). However these higher levels were probably caused by strong prevalence of chronic liver diseases (40%), in patients with atrophic-erosive variety of OLP. No one of these patients was affected by autoimmune liver disease. No differences were noted between atrophic-erosive OLP (Group 1) and hyperkeratotic OLP (Group 2). This study does not confirm the suggestion that patients with OLP may have a generalized immunologic disorder and it also add some evidences that the role of humoral immunity in the pathogenesis of OLP is probably secondary to the cell-mediated reaction against basal keratinocytes. PMID- 8000231 TI - [The use of the teeth in genetic fingerprinting]. AB - Blood, hairs and sperm are tissues currently used in forensic science to carry out DNA fingerprints in the field of individual identification. Our study aims at showing that dental pulp can also be an exploitable DNA source. A quantitative and qualitative DNA investigation on a yield gel with sizing extracted from this tissue shows that the molecule appears to be in a great quantity and of a high molecular weight. The last characteristic allows the use of the restriction fragments length polymorphic technique to make DNA fingerprints, based on the individual variations of the restriction sites disposition, within the DNA molecule, for a given enzyme. Thus, for an enzyme, the length of the restriction fragments obtained and revealed by a probe, is visualized by autoradiograph. According to this technique, we compared the DNA fingerprints obtained on 8 persons with the probe MS43A, from both pulpal and nucleated blood cells. During the extraction of the third molar of each sample, a small quantity of blood was taken in the tooth socket. In the same time DNA was recovered. For a same person, the autoradiograph showed the same pattern for both blood and tooth sample. The DNA profile similitude confirms the possibility of using the tooth for genetic analysis. The interest in using dental tissues as a DNA source of individual identification falls within the particular character of resistance of this organ towards physical or chemical exterior aggressions. The tooth which until now was used in Anthropology and Forensic Science for its morphological aspects could be used this way for genetic study. PMID- 8000233 TI - Detection of HPV DNA by in situ hybridization in benign, premalignant and malignant lesions of the oral mucosa. AB - Evidence has accumulated in recent years that relates certain types of human papillomaviruses (HPV) to the development of some tumors. We use in situ hybridization to study DNA from HPV 6/11, 16/18 and 31/33/35 in 6 squamous papillomas, 18 hyperkeratotic/acanthosis lesions with and without dysplasia (5 and 13 cases respectively) and 27 squamous cell carcinomas of the oral mucosa. HPV DNA was found in 66% of squamous papillomas, 38.4% of hyperkeratotic/acanthosis lesions without dysplasia, 60% of epithelial dysplasia and 37% of squamous cell carcinomas. HPV DNA 6/11 was the most common type found, and in squamous cell carcinomas HPV DNA appear more frequently in well differentiated tumors. PMID- 8000234 TI - Microanatomic features of unilateral condylar hyperplasia. AB - Microanatomic features of unilateral condylar hyperplasia (UCH) are described. The articular surface exhibited clefts with surrounding elevations, and globules varying 0.5-2 microns in diameter. The articular zone presented giant coiled fibers, and the proliferative zone was composed of small round cells. The findings suggest that degenerative changes occur in UCH, both in adult and juvenile forms. PMID- 8000235 TI - [An in toto study of the cholinesterase activity in the visceral cranium of the mouse embryo]. AB - In toto analysis of cholinesterase activity in the cephalic extremity of 9- to 14 day old mouse embryo permits to define four different stages. Stage 1 corresponds to activity in the cephalic neural crest-derived cells. Stage 2 is characterized by activity in the proximal part of both first branchial arches and in the oculomotor blastemata. Stage 3 corresponds to a decrease of the activity, which appears in the area of fusion of several facial processes. Stage 4 corresponds to activity in nervous and muscular blastemata. Cholinesterase activity is thus chronologically varying and implies several differentiating cell populations. PMID- 8000236 TI - In vitro effect of S-adenosyl methionine on ethanol embryopathy in the rat. AB - S-adenosyl methionine (SAM) is a universal methyl donor for biological systems. Chronic consumption of ethanol results in depletion of available SAM and reduces its biosynthesis in the transmethylation pathway. Administration of excess SAM may reduce the embryopathic effects of ethanol. The in-vitro effects of SAM on ethanol embryopathy was investigated by culturing 9.5 day old whole rat embryos for 48 hours in ethanol alone (Group II), 0.05 mM SAM (Group III), ethanol + 0.05 mM SAM (Group IV), ethanol + 0.1 mM SAM (Group V), ethanol + 1 mM SAM (Group VI), and in ethanol + 3 mM SAM (Group VII). In Group VII embryos, cardiovascular, nervous, auditory, visual, craniofacial and musculoskeletal systems were retarded in development; crown-rump length, yolk-sac diameter, as well as morphological scores, were reduced compared to those in embryos treated with ethanol alone (Group II). There were, however, significant differences between Group II and Group IV embryos with respect to crown-rump length, yolk sac diameter and somite number. The mean crown-rump length, yolk sac diameter and somite number in Group II were 2.3 +/- 0.2, 2.8 +/- 0.3 and 22.4 +/- 3.5 respectively, compared to 2.6 +/- 0.2, 3.1 +/- 0.2 and 25.3 +/- 3.1 in Group IV. These results suggest that simultaneous administration of S-adenosyl methionine and ethanol may protect against the embryopathic effects of ethanol. PMID- 8000237 TI - Pulmonary hair embolism in monkeys. AB - Among 184 rhesus and cynomolgus monkeys treated daily for 28 consecutive days by injection into cephalic or saphenous veins, 14 animals (7.6%) had pulmonary emboli with fragments of skin or hair in arterial thrombi or in giant cell granulomas. 167 monkeys (91%) showed lesions at the site of injection, predominantly bleeding and chronic periphlebitis, whereas particles of skin or hair were rare around the veins (2.2%). 2 or 8 weeks after cessation of treatment no pulmonary lesions were observed and healing at the sites of injection was nearly completed in 11 of 12 monkeys allowed to recover. PMID- 8000238 TI - Spontaneous renal lesions in CD-1 and B6C3F1 mice. AB - Incidence and pathology of naturally occurring renal lesions in CD-1 and B6C3F1 mice are evaluated, tabulated, and discussed. In CD-1 mice, most frequent non neoplastic renal lesion was interstitial nephritis (72.6%) followed by amyloidosis (40.6%), mononuclear cell infiltration (23.6%), tubular mineralization (12.8%), cortical cysts (8.2%), hydronephrosis (6.7%), tubular dilatation (5.9%), and tubular degeneration/regeneration (4.7%). Cortical epithelial origin renal cell carcinomas were observed in one male (0.13%) and one female mice (0.13%). In B6C3F1 mice, most commonly occurring non-neoplastic renal lesion was mononuclear cell infiltration (29.8%) followed by tubular mineralization (11.3%), interstitial nephritis (6.8%), tubular vacuolization (4.5%), tubular degeneration/regeneration (2.5%), and cortical cysts (1.3%). Cortical cell adenoma was the only primary renal neoplasm which was observed in one female mice (0.16%). In both strains, other renal lesions were less frequent. PMID- 8000239 TI - Influence of protein calorie malnutrition and fasting on the activities of delta aminolevulinic acid dehydratase and porphobilinogen deaminase in rats. AB - Rats were fed a restricted standard diet (6-8 g daily) for 4 weeks. The erythrocyte activity of delta-aminolevulinic acid dehydratase showed a very expressed decrease (7.9 times) and its hepatic activity diminished more than twice. Porphobilinogen deaminase activity was reduced by 40% and 17% respectively. After a 3-day total food deprivation delta-aminolevulinic acid dehydratase activity remained unchanged in red blood cells, but an increase by 52% was found in the liver. The erythrocyte activity of porphobilinogen deaminase was reduced by 42% and its hepatic activity--by 16%. PMID- 8000240 TI - "Wavy ribs". A reversible pathologic finding in rat fetuses. AB - A literature of 74 scientific papers addressing the occurrence of "wavy ribs" in fetuses of small rodents has been collected with the support of a computer assisted search on MEDLINE, TOXLINE, BIOSIS and EXCERPTA MEDICA systems (1982 1993) and has been critically examined. Numerous compounds of a large variation in chemical structure and biological activity, if given to pregnant rats during the later period of organogenesis, are known to cause "wavy ribs" in their fetuses, a reversible pathologic finding which is rarely observed in untreated controls. According to literature, causative factors, like delayed development of alkaline phosphatase, decreased fetal protein, dietary contents, maternal toxicity, renal loop diuretics, myometrial constriction, endocrine disturbances and beta-adrenoceptor stimulation or blocking have been observed and discussed, but, a general explanation for the lesions is still missing. Therefore, the following hypothesis may be added: the high doses used in reproductive toxicology may induce maternal and placental circulatory disturbances leading to reductions in fetal serum proteins, with delayed development of osteoblast progenitors and low fetal serum alkaline phosphatase in the day 17-20 fetus. Normalization of the neonate's homeostasis (serum protein) leads to enhanced ossification and concomitant bone repair until weaning. PMID- 8000241 TI - Changes induced by treatment with aromatase inhibitors in testicular Leydig cells of rats and dogs. AB - Treatment of male rats and dogs with CGP 32,349 (formestane), a steroidal aromatase inhibitor, and CGS 20,267 (letrozole), a non-steroidal aromatase inhibitor, induced different alterations in testicular interstitial Leydig cells in the two species. Whereas in dogs Leydig cells were hypertrophic and hyperplastic, in rats either no effect (CGS 20,267) or atrophy of Leydig cells (CGP 32,349) was reported. The different response of the two species can be explained by different regulating mechanisms of gonadotropin secretion by the anterior pituitary. PMID- 8000242 TI - Simultaneous induction of liver cirrhosis and hepatocellular carcinomas in F-344 rats: establishment of a short hepatocarcinogenesis model. AB - The relationship between liver cirrhosis and diethylnitrosamine (DEN)-induced hepatocarcinogenesis in male F-344 rats was studied. Hepatic cirrhosis was produced by combined administration of CCl4 (0.5 ml/kg b.w. by gavage, three times a week) and phenobarbital (PB) (0.05% in drinking water, continuously for 6 weeks), while the carcinogenic nitrosamine compound was given either preceding or following CCl4 + PB treatment at a single dose of 200 mg/kg b.w., ip. Liver lesions were evaluated histologically at the end of the 4th month. The established cirrhosis completely prevented the formation of hepatocellular carcinomas (HCCs), however, CCl4 + PB posttreatment resulted in a strong enhancing effect on DEN-hepatocarcinogenesis: 16 weeks after initiation severe cirrhosis and HCCs occurred simultaneously in more than 90% of the animals. Although the explanation of this highly accelerated carcinoma formation is not known at present, the authors hypothesize that the modulation of the drug metabolizing enzyme system might play a central role in this profoundly altered host response. PMID- 8000243 TI - Experimental idiopathic dilated cardiomyopathy under low-calcium condition. AB - Administration of long-term, low-dose Na2EDTA leads to moderate or severe thinning of the right ventricular wall with or without rupture. These morphological manifestations are known to be site-dependent on the constriction of pulmonary arteries (Yamaguchi et al. 1993a). They sometimes ensue from aneurysmal dilatation and/or plexiform-like-lesion in a pulmonary artery (Yamaguchi et al. 1993b). The present contribution reports that experimental animals who survived for a longer period, maximum for 6 months, showed dilatation of the left ventricle with a mode-rately thin ventricular wall as well as right ventricular changes, which are similar to the morphological manifestations in idiopathic dilated cardiomyopathy. PMID- 8000244 TI - Light-induced retinopathy in the albino rat in long-term studies. An immunohistochemical and quantitative approach. AB - Retinas from male Wistar rats which were housed during a long-term drug safety study at short, medium and long distance from a fluorescent light source were examined. Retinal atrophy was pronounced in the central retina of rats housed closest to the light source, and was characterized by a loss of photoreceptor cells and of S-antigen immunoreactivity in the outer nuclear layer (ONL), absence of synaptophysin immunoreactivity in the outer plexiform layer (OPL), decrease of the number of nuclei in the inner nuclear layer (INL), astrocytic proliferation, and Muller cell activation. The peripheral retina of these rats had a laminated architecture, although the number of photoreceptor cells and nuclei in the INL was reduced. Retinas from rats housed a medium distance from the light source did not have any apparent histological or immunohistochemical changes, except for a lower number of photoreceptor cells and nuclei in the INL. The rats housed a long distance from the light source had the highest number of nuclei in the ONL and INL of the central and peripheral retina, and were used as control group. Our data indicate that retinal atrophy occurs in male Wistar rats maintained under light conditions currently used in long-term toxicity studies, and suggest that photoreceptor cell loss is followed by trans-synaptic anterograde degeneration of neurons in the INL, astrocytic proliferation and Muller cell activation. PMID- 8000245 TI - Experimental study on the hyperplasia of juxtaglomerular cells under low-dose, long-term administration of calcium chelating agents. Similar to the morphological manifestation of Bartter's syndrome. AB - Bartter's syndrome is a genetic disorder which has very rarely been clinically encountered. However, it is of specific interest with respect to the hormonal layer of the kidney, including renin, angiotensin and aldosterone as well as biological alteration of the various electrolytes. The fundamental morphological manifestation of this disorder is known to be hyperplasia of juxtaglomerular cells, although, until now, no experimental studies on this condition have been reported. Demonstrated in this initial study is the remarkable hyperplasia of the juxtaglomerular cells in all terminal portions of the afferent glomerular arterioles situated near the hilum of the glomerular tuft, using a low-dose, long term administration of calcium chelating agents. This hyperplasia reported in this paper may lead to a new procedure in the analysis of this syndrome. PMID- 8000246 TI - The male reproductive organs in experimental Chagas' disease. III. Plasma testosterone and accessory sex glands in the acute phase of the disease. AB - Male Wistar rats were injected i.p. with 2 x 10(5) trypomastigotes of the Bolivia strain. Fifteen days later, few parasite nests were observed in the fibromuscular layer surrounding the seminal vesicle acini of chagasic animals and no parasites were detected in the testis and ventral prostate. A significant decrease was observed in the absolute weight and fructose content of the seminal vesicle and ventral prostate of chagasic rats, which also presented a sharp decrease in plasma testosterone levels. PMID- 8000247 TI - The cellular reproduction in physiological and reparative liver regeneration. AB - The liver regeneration of male rats was examined autoradiographically under physiological and reparative conditions. The reparative regeneration was induced by a single injection of allylalcohol intraperitoneally. In both forms of regeneration a displacement of tritiated thymidine-marked hepatocytes from the periportal field to the perivenous field of the liver acinus could be recognized. The velocity of the cell migration after allylalcohol administration was higher than under physiological conditions. Physiological and reparative liver regeneration do not exclude each other but obviously coexist. A more intensively to be examined hepatocellular stem cell concept gains importance. PMID- 8000248 TI - Renal excretion and renal tubular transport of p-aminohippurate (PAH) in methimazole treated, hypothyroid rats of different ages. AB - Thyroid hormone deficiency following treatment with methimazole for 7 days does not reduce PAH secretion in renal tubular cells as expected from data in thyroid hormone treated rats. This treatment with methimazole causes an increase in renal excretion of PAH in rats of various age groups, statistically significant in 5-, 10- and 20-day-old rats. In 20-day-old, methimazole treated rats the increase in renal excretion of PAH is obviously caused by a higher transport rate in renal tubular cells, proved also in 33-day-old rats. An increased filtered fraction of PAH in 5- and 10-day-old rats could be the reason for the rise in renal excretion of PAH after repeated treatment with methimazole. The mechanism of renal effects of methimazole treatment remains unclear. PMID- 8000249 TI - [Significance of HCV infection for post-transfusion hepatitis]. AB - Five years ago the hepatitis C virus has been first characterized, and diagnostic tools have been developed to demonstrate acute or chronic infection. At least six different genotypes have been identified. After a primary HCV infection reinfection with other genotypes seems to be possible. The serological tests currently available cannot differentiate between acute, past or chronic hepatitis C. Blood donors which show a reactive result by ELISA should be retested by a confirmatory assay and PCR for the demonstration of viral RNA to exclude or demonstrate persistence of HCV. Systematic screening of blood units for antibodies to HCV reduced the posttransfusion hepatitis up to 95%. However, there is still a risk for acquiring posttransfusion hepatitis C which is actually calculated to be 1:20,000 up to 1:50,000. PMID- 8000250 TI - [Hepatitis B--significance for transfusion medicine]. AB - OBJECTIVE: To describe the present risk for transfusion-associated hepatitis B in Germany or in countries with low hepatitis B incidence, respectively. DATA SOURCES: Selected relevant publications since 1978, own data. RESULTS: Despite donor selection and HBsAg screening hepatitis B infections after transfusion are reported to occur with a frequency of 0.2-1.8%. The most important source are probably donors who are viral carriers despite lacking HBsAg. This serological pattern is often found in individuals showing anti-HBc as only marker for a hepatitis B infection. About one third of these people are thought to be carriers of HBV. How many of these individuals belong to the blood donor population in Germany is at present unknown. CONCLUSIONS: Studies evaluating the frequency of HBsAg-negative HBV carriers among blood donors are urgently required. Results of such investigations will show whether the introduction of additional tests, such as screening for anti-HBc, will further diminish the risk for posttransfusion hepatitis B. PMID- 8000251 TI - [Transmission of parvovirus B19 by blood and blood components]. AB - OBJECTIVE: To determine the clinical significance of parvovirus B19 (B19) and the potential risk of transmission by blood or plasma products. Procedures to avoid this transmission are discussed. DATA SOURCES AND SELECTION CRITERIA: Known physico-chemical data of autonomous parvoviridae, and studies on the incidence of B19 in blood or plasma products, were considered. Data on B19 infection published by the author and/or other investigators. RESULTS: B19 occurs endemically in Germany. The incidence of B19 virus-positive blood donations is approximate 0.01 0.03%. Despite using virus-inactivating procedures transmission of B19 by clotting factor concentrates cannot be excluded at present. CONCLUSIONS: Transmission of B19 virus by blood or plasma products can be avoided by testing single donations for B19-specific antibodies by enzyme-immunoassay or B19 DNA by polymerase chain reaction. PMID- 8000252 TI - Diagnosis and epidemiology of transfusion-associated human cytomegalovirus infection: recent developments. AB - OBJECTIVE: The prevention and diagnosis of transfusion-associated HCMV infection has to address different questions: Is the blood donor potentially infections? Is the transfused recipient undergoing an active primary or secondary infection? DATA SOURCES: International literature (Current Contents Life Sciences) and reports of our study-group. SELECTION CRITERIA: Original articles in English and German. RESULTS: Monocytes have been identified as the major site of latency of human cytomegalovirus (HCMV) in peripheral blood. High seropositivity rates are observed in polytransfused individuals, intravenous drug users, organ transplant recipients, maintenance hemodialysis patients, homo/bisexuals and prostitutes. Although, there have been important developments in order to improve the sensitivity of the ELISAs for the diagnosis of active HCMV infection, serologic testing often fails to detect IgM and IgA antibodies in immunocompromised patients. Rapid virus isolation, structural antigen detection and DNA amplification by PCR in peripheral blood monocytes have considerably improved diagnosis of acute HCMV infection in neonates, organ transplant recipients and AIDS patients. Due to the low correlation of HCMV DNA detection and HCMV disease, PCR testing is actually not recommended for the monitoring of high risk patients and screening of infectiosity of blood components. CONCLUSIONS: As a consequence numerous improvements in serological, virological and molecular methods, a more efficient prevention and diagnosis of transfusion-associated HCMV infection has become possible. PMID- 8000253 TI - [Transmission of parasites by blood transfusions and organ transplantation]. AB - OBJECTIVES: The purpose of the present study consists in an updated review concerning the transmission of protozoa and worms by blood transfusion and organ transplantation. Prophylactic regimens and possible modifications will be discussed. DATA SOURCES: The literature devoted to tropical medicine in recent years was screened and a search on Medline was performed. Relevant review articles were selected. RESULTS: Transfusion induced malaria and--especially in Latin America--transfusion associated Chagas' disease are the most important of these diseases. Prophylaxis of transfusion malaria is different in different countries, it is based primarily on donor selection and immunodiagnostic examinations. CONCLUSIONS: It is recommended that the German guidelines for prevention of transfusion malaria should be modified and that a donor selection should also take place concerning Chagas' disease. PMID- 8000254 TI - [Bacterial infection within the scope of hemotherapy]. AB - OBJECTIVE: The purpose of this article is to present a survey of bacterial infections caused by hemotherapy. DATA SOURCES: Original papers as well as review articles from international investigations based on literature data banks. RESULTS: As there exist only a few studies about transfusion complications caused by bacteria you only can find sporadic reports. Surely immunocompromised recipients have high risk to be hurt. Causing bacteria are various but Staphylococci, Yersinia, Serratia and Pseudomonas species often are found. Especially platelet concentrates give higher infection risk because storage at room temperature is obligatory. This fact makes growth conditions more comfortable. Strict hygienic measures, extension of donor screening and pointed quality control are capable to decrease the risk of transfusion complications. CONCLUSIONS: Exact indications and a clear strategy evaluating the transfusion reports and routine bacteriological control are necessary to prevent infections caused by hemotherapy. PMID- 8000255 TI - [Risk of infection in hemotherapy]. AB - For some years, public interest has focused on transfusion-transmitted HIV. German blood donors are now selected and show only very low incidences in HIV and hepatitis. Only one per million donors seems to transmit HIV. The remaining risk of post-transfusion hepatitis is estimated to range between 1:10,000 and 1:100,000. Some new diagnostic tests might reduce the danger of transfusion transmitted infections. Screening donors for anti-HBc is a well accepted tool to decrease post-transfusion hepatitis B. The HIV-p24-Ag test is expensive and only of doubtful value. Donor recruitment should be improved in future. PMID- 8000256 TI - [Benefits and risks of autologous blood donation]. AB - Aim of this review is to compare benefits and risks of autologous blood transfusion with special emphasize on donation and retransfusion risks. Autologous blood transfusion may reduce the transfusion-associated mortality by 70%. Another advantage of preoperative autologous blood donation is the increase in erythropoiesis. Immunologic and viral infectious complications have not been reported with transfusion of autologous blood. On the other hand, autologous blood predonation is associated with risks during donation and retransfusion. Reactions due to routine autologous predonation of blood have been examined in several studies. Mild and moderate reactions occurred in similar frequencies with autologous predeposit and homologous donations, respectively. High risk autologous predonation has also been successfully performed in patients with end stage heart or lung disease and in pregnancy. No data could be retrieved concerning the frequency of retransfusion-associated risks, e.g., clerical error or contamination of blood products. Bacterial contamination of autologous blood is published only in case reports. Autologous blood transfusion has minor impact on hospital mortality since overall risk of transfusion is low compared to mortality of anesthesia and surgery. However, no reliable criteria exist by which rare severe complications such as unstable angina or transient ischaemic attacks could be predicted. In cases with minor blood loss isovolaemic haemodilution should be performed instead of autologous predeposit. Autologous predonation should be done whenever other forms of autologous transfusion are not sufficient to exclude homologous transfusion. PMID- 8000257 TI - [Possibilities of family blood donation for children and adults]. AB - Directed donations are refused by the most transfusion services for some reasons. At first, voluntary donation is questionable when relatives will be used as blood donors. This fact leads to a higher risk of infections compared with a third party donation. In some rare instances, directed donations may be necessary or beneficial for the recipient. In all these cases, donors must be selected according to federal and institute guidelines. Production, storage, administration and distribution of blood products determined for a certain recipient require many personnel, material and logistic energy. These results in higher costs which have to be borne by the recipient himself. Cost of directed donations are in contrast to their benefit and in contrast to more cost effectiveness. PMID- 8000258 TI - [Transfusion-associated HIV infection]. AB - OBJECTIVE: Estimating the risk of HIV transmission by blood or inactivated plasma transfusion. A discussion of the methods and techniques for the diagnosis of HIV infection in blood donors. DATA SOURCES: Reports in German and English on this topic as well as own experiences of the authors. SELECTION CRITERIA: No specific selection criteria. RESULTS: Transfusion associated HIV infection may be prevented by donor selection, the very efficient anti-HIV testing, by p24-antigen testing that may detect some anti-HIV negative donations especially during the early time of seroconversion and by more recent introduced techniques like polymerase chain reaction (PCR) and signal amplification assay (SAA). PCR and SAA are under development and until now not sensitive and specific enough to contribute significantly to an earlier detection of HIV infected blood. Procedures for the inactivation of HIV in plasma or whole blood have been described. Until now use of psoralens, methylene blue or direct UV irradiation may reduce viral load but have not definitely been proven by clinical trials to be 100% efficient. CONCLUSIONS: To minimize transfusion associated HIV infection in future years reduction of total amount of transfused units, restriction to regional donor recruiting and further refinement of tests will be necessary. A 100% safety of blood transfusion for infectious agent cannot be achieved, especially considering new agents and further spread of until now geographically restricted viruses. PMID- 8000259 TI - [Virus inactivated plasma]. AB - Two different virus inactivated plasma preparations are available in Germany. Methylene blue ephotoxidized (MB) plasma is plasma from a single donation, which is photoxidized using 1 microM methylene blue and visible light (1 hour 60,000 Lux). Photochemical inactivation reduces HIV by at least 5 log10, but also fibrinogen is altered. To date, the clinical significance of this finding is still unclear, since prospective clinical studies are lacking. Solvent detergent (SD) plasma is manufactured from a pool of about 2000 plasma donations, and triton-X-100 and tri-n-butyl-phosphate (TNBP) are added for virus inactivation. HIV and hepatitis viruses are thus reduced by 5 to 6 log10. SD treatment reduces protein S and alpha-2-antiplasmin by about 40%. Clinical studies have already demonstrated, that SD plasma is comparable with untreated, native fresh frozen plasma in terms of efficacy. PMID- 8000260 TI - [Possibilities of virus inactivation of pooled fresh plasma with tri-n butylphosphate (TNBP) detergents (SD procedure)]. AB - Treatment with tri-n-butyl-phosphate and detergent (SD-treatment) leads to efficient inactivation of viruses having a lipid enveloped surface, like hepatitis B virus, hepatitis C virus and human immunodeficiency virus, that are presently the most transfusion relevant viruses in Germany. Other lipid enveloped viruses of the herpes group like cytomegalovirus and Epstein-Barr virus are inactivated as well. Non-enveloped viruses like parvovirus B19 and picornaviruses are not inactivated by SD-treatment. Future inactivation of blood components like plasma and blood products will be a combination of SD- and heat-treatment. Keeping single plasma units in quarantine for 6 months is one of the alternatives in elevating transfusion safety. For transfused blood the safety against infectious agent will continue to depend on the effectiveness of donor selection and the efficacy of testing. PMID- 8000261 TI - [Current status of viral safety of virus inactivated factor VIII and IX concentrates in treatment of hemophilia]. AB - Based on the results of seven ICTH-controlled PUP studies only the virus inactivating procedures by pasteurization (60 degrees C for 10 h), tri-n-butyl phosphate/detergent treatment, and vapor heating (60 degrees C for 10 h and 1,200 mbar) have prevented the haemophilic patients from infections with hepatitis B, C and HIV. After the disaster of the HIV infection in haemophilic patients at the beginning of the 80's the factor concentrates given today seem to be safe for virus infections during substitution therapy. To prove this high therapeutical standard there is a need for a prospective long-term pharmaco-vigilance study under the auspices of an independent body such as the Medical Advising Committee of the National Haemophilia Society or other scientific organisations. PMID- 8000262 TI - [HIV safety of commercially produced human plasma proteins]. AB - An important aim of the commercial manufacturing of human plasma proteins to be used as therapeutics is the HIV-safety of such products. This aim will be achieved by using (1) plasma donations of carefully selected, healthy donors, (2) by testing of each donation according to national and international requirements for antibodies or antigens specific for certain viruses, (3) by eliminating viruses by different purification procedures of the manufacturing process and (4) by inactivating viruses by a specific method included in the production process. Due to the current discussion in Germany this paper will particularly focus on HIV. As an example, the experimental studies of the manufacturing process of pasteurized factor VIII proving the elimination of HIV by various stages of the production process and its complete inactivation by pasteurization (= 10 h heat treatment of the stabilized, aqueous factor VIII-solution at 60 degrees C) is discussed. A cumulative reduction factor of > 10(16) is achieved by the different stages of the entire manufacturing process, including pasteurization. In fact, the HIV-inactivation is by some orders of magnitude higher than demonstrated by the special inactivation experiment, because the heat treatment of the production procedure consists of 10 hours instead of one hour as needed under experimental conditions for the complete inactivation of HIV. If the manufacturing procedure of a human plasma protein contains a method which completely inactivates HIV and which in total results in a cumulative reduction factor of > 10(12) for HIV, the final product is regarded as being free of infectious HIV. PMID- 8000263 TI - Sternitis and mediastinitis after coronary artery bypass grafting. Analysis of risk factors. AB - As part of a quality control program, we analyzed possible risk factors in the development of sternitis and mediastinitis after coronary artery bypass grafting. From 1 January 1990 through 31 December 1991, 1,368 consecutive coronary artery bypass grafting procedures were performed at our institution, either alone or in combination with other procedures. Twenty-three patients (1.7%) developed sternitis and/or mediastinitis; 7 (30.4%) of these patients died in an early postoperative phase. Univariate analysis revealed the following statistically significant (p < or = 0.05) risk factors: perfusion time, length of stay in operating room of longer than 5 hours 30 minutes, presence at the operation of a certain surgical resident, revision for bleeding, and postoperative mechanical ventilation lasting longer than 72 hours. After multivariate analysis, statistically significant independent risk factors were: diabetes mellitus, recent cigarette-smoking, reoperation, presence of a certain surgical resident at the operation, revision for bleeding, and length of mechanical ventilation of longer than 72 hours. The use of both internal thoracic arteries was not, in this study, shown to be an independent risk factor. We conclude that although the technique of using both internal thoracic arteries for myocardial revascularization carries no extra risk by itself in the development of sternitis or mediastinitis, associated factors such as prolonged stay in the operating room and reoperation could be responsible for a higher frequency of sternitis mediastinitis in patients who have undergone this procedure. Therefore, it is advisable to use this technique selectively in high-risk patients. Close surveillance and reporting of wound infections is mandatory to detect risk factor related to the surgical staff (such as Staphylococcus aureus dissemination). PMID- 8000264 TI - Echocardiographic evaluation of anuloplasty rings. Comparison of continuity equation and pressure half-time methods. AB - This study was undertaken to compare pressure half-time and continuity equation methods in the postoperative evaluation of anuloplasty rings. We performed 2 dimensional echocardiography and Doppler studies in 39 patients who had undergone valve repair for mitral regurgitation. In patients with a pressure half-time of 110 msec or more (9/39), there was no significant difference in calculated valve area between the 2 methods (p = 0.696). A significant difference was shown between the 2 methods (p < 0.001) in patients with a half-time less than 110 msec (30/39). When patients were classified according to the type of ring they had received, no significant difference was noted between the 2 groups with regard to peak and mean mitral gradients. In patients placed in subgroups according to half times of less than 110 msec and half-times of 110 msec or more, no difference was noted between groups in terms of mean mitral gradient, presence of mitral regurgitation, left atrial size, left ventricular function, or heart rate. The continuity equation appears to provide much more homogeneous results in the calculation of valve area in patients who have undergone valvular repair for mitral valve regurgitation. PMID- 8000265 TI - Short-term results of bovine internal mammary artery use in cardiovascular surgery. AB - Over a 14-month period, 28 bovine internal mammary arteries (Bioflow, Bio Vascular, Inc.; St. Paul, Minnesota, USA) were implanted in 20 patients at our institutions. In 8 patients, the bovine internal mammary artery was used to bypass coronary vessels: in 4 of these patients, coronary artery bypass grafting was performed because of coronary disease (1 type-I aortic dissection); in the other 4 (all with aortic dissection), the modified Bentall technique was used for coronary artery reimplantation. In the remaining 12 patients, the bovine artery was used in vascular surgery: as a graft for lower-extremity occlusive disease (4 patients), arteriovenous fistula (2 patients), and aorticorenal bypass (1 patient); and as a patch to the carotid bifurcation or the common femoral artery in association with endarterectomy (5 patients). The 21 bovine grafts were all 5 mm in diameter; the 7 bovine patches were 4 mm. Of the 8 coronary bypass patients, 2 who underwent coronary artery bypass grafting had acute postoperative myocardial infarctions, and 2 who underwent the modified Bentall technique died in surgery. Follow-up angiography showed complete bovine internal mammary artery graft occlusion in 2 patients; 2 symptom-free patients refused examination. Of the vascular surgery patients, 1 with mild left leg claudication had graft occlusion, shown by angiography, 4 months after surgery. Renal scintigraphy performed in the patient with aorticorenal bypass 4 months after operation showed no blood flow to the kidney. Two patients died for reasons unrelated to bovine mammary artery grafting. The remaining patients are well and free of complications. In view of the high incidence of early occlusion, we do not recommend use of the bovine internal mammary artery graft in coronary surgery. In vascular surgery, the results are more encouraging; however, studies comprising a larger number of patients and longer follow-up are needed to determine whether the use of the bovine internal mammary artery graft can be recommended. PMID- 8000266 TI - Polycythemia and the heart. A review. AB - Thrombosis of the coronary arteries, heart chambers, and great vessels is a complication of polycythemia. Previously, the treatment of coronary thrombosis in the presence of this disease was based on exchange phlebotomy. However, the development of efficient thrombolytic agents, emergency catheterization techniques, and coronary artery bypass surgery may make phlebotomy obsolete. PMID- 8000268 TI - The "fully no-touch" technique for the internal thoracic-coronary artery anastomosis. AB - Extreme technical accuracy is crucial in coronary artery surgery. Although late graft patency depends mostly upon the patient's own biochemical status in chronic ischemic patients who have undergone elective surgery, graft disease is certainly promoted by an inaccurate technique or by careless arterial harvesting, which may cause both intimal lesions and anastomotic strictures. We describe a technique of internal thoracic-coronary artery anastomosis that fully prevents contact between vessels and surgical instruments. In order to enable the suturing of a fully dilated vessel, intracoronary papaverine is injected into the clamped aortic root while the heart is still beating and before systemic cooling begins. The suturing technique applies some microvascular principles, the chief being a high number of stitches incorporating the least amount of tissue, to avoid bulk. PMID- 8000267 TI - Dobutamine stress echocardiography in clinical practice with a review of the recent literature. AB - Stress echocardiography has been developed in recent years as an effective noninvasive test for the detection and assessment of coronary artery disease. This method combines exercise with 2-dimensional echocardiography, which can assess regional and global left ventricular function during stress. Dobutamine infusion, a pharmacologic means of producing cardiovascular stress, appears to be an excellent alternative to exercise in echocardiographic studies. Currently, it is reserved for patients who cannot exercise at a meaningful level because of advanced age, physical deconditioning, or other factors. This review evaluates the current clinical application of dobutamine stress echocardiography and compares its efficacy with that of exercise echocardiography and nuclear perfusion imaging. PMID- 8000269 TI - Initial experience of mitral valve replacement with total preservation of both valve leaflets. AB - We compared a series of 7 consecutive patients who underwent mitral valve replacement with preservation of both leaflets to a control group of 97 patients who underwent standard mitral valve replacement at our institution during the same period. Use of inotropic drugs and duration of postoperative intensive care were compared and shown to be markedly reduced in the study group; however, statistical analysis was not applied due to the small number of patients. Comparison of the available pre- and postoperative echocardiographic values showed a decrease in left ventricular end-diastolic and end-systolic diameters in patients with preserved leaflets, particularly in those with mitral regurgitation of degenerative origin. PMID- 8000270 TI - Transmyocardial laser revascularization. Anatomic evidence of long-term channel patency. AB - Transmyocardial laser revascularization, a new surgical technique, is being tested in patients with chronic obstructive coronary artery disease that is refractory to conventional revascularization techniques and to maximal medical therapy. During the operation, which is performed on the beating heart through a left thoracotomy, a high-energy CO2 laser is used to bore transmural channels (1 mm in diameter) into the left ventricle. Each high-energy laser pulse is delivered during end diastole and transects the heart within 10 to 60 msec. The operation is based on the theory that blood will flow directly from the left ventricle into the channels and then into the myocardial vascular plexus. Restoring perfusion should alleviate ischemia in potentially viable myocardium and improve ventricular function. Recently, one of our patients died 3 months after transmyocardial laser revascularization of causes unrelated to the operation. Histologic analysis enabled us to obtain, for the 1st time, anatomic evidence of patent laser channels. Routine staining of cardiac tissue with hematoxylin and eosin revealed multiple patent channels, running perpendicular to and interconnecting with the native vasculature. Although reactive fibrous scar tissue had caused narrowing of the original laser tract, the channels had endothelialized and they contained red blood cells. These findings suggest that the laser channels were functional. We report this interesting case and briefly discuss the anatomic and physiologic phenomena involved in establishing camerosinusoidal blood flow by use of transmyocardial laser revascularization. PMID- 8000272 TI - Spontaneous cholesterol embolization. A rarely reported entity. AB - Cholesterol embolization sometimes occurs after invasive procedures involving manipulation of the aorta or its major branches, and less commonly occurs after thrombolytic therapy for acute myocardial infarction. Rarer still is spontaneous cholesterol embolization, a case of which we now report. Our patient experienced peripheral embolization, the origin of which was traced to the infrarenal aortic segment and the common iliac vessels. Aortoiliac reconstruction was successful; we believe that surgical management of this condition should be performed in selected cases. PMID- 8000271 TI - Isolated right atrial compression as a late sequela of aortic valve replacement. AB - Isolated right atrial compression occurred 31 months after aortic valve replacement. Aortic bleeding contained by adjacent pericardium produced a pseudoaneurysm and local atrial tamponade. Transthoracic echocardiography could not distinguish the extracardiac hematoma from an intra-atrial thrombus, temporarily misleading investigators. PMID- 8000273 TI - Mycotic aneurysm of the left anterior descending coronary artery after aortic endocarditis. A case report and brief review of the literature. AB - This report concerns a 29-year-old man with recent Streptococcus viridans endocarditis on a bicuspid aortic valve who was found to have a mycotic aneurysm of the left anterior descending coronary artery and infective erosion and thinning of the posterior wall of the ascending aorta 1.5 to 3.5 cm above the origin of the left coronary artery, a combination of lesions not previously reported. Mycotic aneurysm of the coronary arteries affects less than 1% of patients with infective endocarditis, and there are few reports of the management of these rare lesions. The surgical management of this patient is presented with a brief review of the available literature. PMID- 8000274 TI - Unusual subclavian steal phenomenon. AB - A patient who had undergone myocardial revascularization with a saphenous vein graft to the left anterior descending artery and a left internal thoracic (mammary) artery graft to the 1st diagonal branch presented with an unusual form of subclavian steal syndrome. Occlusion of both the left subclavian and the left anterior descending arteries caused retrograde flow through the internal thoracic artery to the distal subclavian artery; the blood flow was supplied by the vein graft via the distal left anterior descending artery and diagonal branch. PMID- 8000275 TI - Septal dissection in a ventricular septal rupture. PMID- 8000276 TI - Circumferential dissection of the ascending aorta with intimal intussusception. PMID- 8000277 TI - Effect of beta 1-adrenoceptor blockade in rats at 5 bar ambient pressure. AB - Conscious rats exposed to 5 bar (500 kPa) ambient pressure show increased total myocardial blood flow (TMBF) and enhanced cardiac contractility in spite of unaltered mean arterial pressure (MAP), heart rate (HR), and cardiac output (CO). Four groups of awake, adapted rats were given injections of atenolol at 1 bar air or 5 bar normoxic N2, or both. Atenolol injected at 1 bar caused a marked reduction of HR, MAP, peak left ventricular pressure (LVP), and rate of LVP rise (+dP/dt) and fall (-dP/dt). In spite of beta 1-adrenoceptor blockade, ambient pressure rise increased HR, LVP, +dP/dt, -dP/dt, TMBF, and calculated cardiac O2 consumption (P < 0.05). A second atenolol injection at 5 bar caused a brief reduction in HR but did not affect cardiac contractility. Rats receiving the first atenolol injection at 5 bar demonstrated unchanged TMBF. We conclude that beta 1-adrenoceptor blockade does not annual the increase in cardiac contractility associated with hyperbaria. PMID- 8000278 TI - Assessment of visual contrast sensitivity in hyperbaric oxygen. AB - Hyperbaric oxygen therapy is used in ophthalmology in ischemic pathologies of the anterior and posterior segments. Our experiment was done on a healthy group of volunteers aged between 10 and 50 yr. We examined the subject's vision before and after acute HBO exposure (60 min at 2.5 atm abs with pure oxygen) to verify whether vasoconstriction induced by hyperoxemia can influence eyesight. We measured the psychophysical determination of the threshold contrast according to Maione-Maffei's zebra test. The results demonstrated that contrast sensitivity is significantly improved for almost all the studied frequencies in normal subjects after acute HBO exposure. We hypothesize that the visual system has a reserve which is activated by an improvement of retinal oxygenation. PMID- 8000279 TI - A histopathologic and immunocytochemical study of the spinal cord in amateur and professional divers. AB - To clarify the influence of diving activity on the central nervous system, we studied 10 amateur and 10 professional deceased divers with emphasis on the presence of subacute or chronic pathologic changes in the spinal cord. Of the 10 professional divers (median age 38 yr; range 29-52; median experience in excess of 13 yr), 7 were experienced saturation divers. Five had dived to a maximum depth of 150 meters of seawater, the 2 others to 300 and 500 msw, respectively. Five of the professional divers had experienced decompression sickness. The experience of the amateur divers (median age 29 yr; range 17-51) varied from a few dives to many years of recreational diving. The spinal cords were formalin fixated and routinely processed for neuropathologic examination, which included light microscopy after immunostaining for glial fibrillary acidic protein and monocyte-macrophage-microglial markers. The microscopic examination did not reveal previous spinal cord damage. Thus, diving activity, saturation diving to extreme depths included, does not in itself seem to lead to necrosis, degeneration, or scar formation in the human spinal cord. PMID- 8000280 TI - A test for variations in individual sensitivity to hyperbaric oxygen toxicity. AB - It has been suggested that some individuals have above-average sensitivity to hyperbaric oxygen toxicity. An extensive human study completed at the Naval Experimental Diving Unit (NEDU) tested human tolerance to HBO and raised the possibility of assessing this hypothesis. In a group of 113 subjects given multiple exposures, some developed no symptoms of O2 toxicity while others developed symptoms on several occasions. The subjects in this study received unequal numbers of exposures of different depths and durations however, and it was not obvious how to determine unusual sensitivity. To assess the influences of chance vs. differences in sensitivity on the outcome of this experimental series, we performed a Monte Carlo simulation in which the experimental design was duplicated and the sensitivity hypothesis was evaluated statistically. The number of subjects giving rise to any symptoms and the distribution of individuals having symptoms on multiple occasions were evaluated. The simulation showed that the NEDU results were not unusual: nearly one quarter of the time the observed pattern of multiple symptoms could have been expected due to chance alone. The power of this simulation would have permitted detection of sensitivity factors 10 times (or greater) normal in 20% of the subjects at least half of the time. PMID- 8000281 TI - Effect of air, heliox, and oxygen breathing on air bubbles in aqueous tissues in the rat. AB - Our purpose was to examine the behavior of air bubbles in three non-lipid tissues (skeletal muscle, tendon, and the anterior chamber of the eye) during breathing of air, helium-oxygen (heliox, 80:20), or oxygen. Air bubbles were injected into skeletal muscle or tendon in rats after decompression from a 1-h air exposure at 3.5 atm abs (355 kPa) or into the anterior chamber of the rat eye without any previous pressure exposure. The bubbles were studied by photomicroscopy at 1 atm abs (101 kPa) during either air breathing or during air breathing followed by heliox or O2 breathing. Muscle: during air breathing, all bubbles initially increased in size for a period of 55-100 min after decompression and then started to shrink. Both heliox and O2 breathing increased the shrinking rate as compared to air. Bubble size decreased more rapidly during O2 than heliox breathing. Tendon: during air breathing, bubble size decreased at a constant rate; in one bubble the decrease was preceded by a small increase. During heliox breathing most bubbles decreased faster than during breathing of air. O2 breathing caused a short-term increase in bubble size in 4 out of 10 bubbles. Otherwise, the shrinkage rate was increased in six bubbles and uninfluenced in four bubbles during breathing of O2. Rat eye: during air breathing all bubbles shrank in the observation period. When heliox breathing was started, all bubbles transiently grew for 10-35 min, after which they began shrinking faster than during air breathing. When O2 breathing was started, five out of seven bubbles initially grew or stopped shrinking for 5-15 min, after which they decreased in size faster than during both air and heliox breathing. We conclude that breathing of either heliox or O2 will cause air bubbles in aqueous tissues to disappear faster than during breathing of air. Since heliox breathing promoted bubble shrinking in both muscle and tendon, gas exchange was probably not primarily limited by extravascular diffusion in these aqueous tissues. The present experiments suggest that heliox breathing at 1 atm abs may not exacerbate limb bends. PMID- 8000282 TI - Unexplained muscle swelling in divers. AB - Muscle swelling in divers may represent a previously unreported form of decompression sickness. It shows marked, brawny swelling of skeletal muscle which clinically most suggests muscular lymphedema in its woody texture to palpation and unresponsiveness to recompression. Four episodes of unexplained muscle swelling in commercial divers are presented, none apparently resulting in muscular injury. PMID- 8000283 TI - Calculated thermal conductivities and heat flux in man. AB - Using data compiled by the Brussels Cadaver Analysis Study on 13 unembalmed cadavers, this study examined the validity of assumptions often made concerning the role of the skin and adipose tissue layers in thermal insulation in vivo. Skin thickness was previously reported to vary from 0.35 to 2.55 mm, depending on the site of measurement and gender of the subject. Assuming a thermal conductivity of 0.70 x 10(-3) kcal/(cm.s-1.degree C-1) for the skin, heat flux across the skin would vary between site and gender in the order of 7.5 times, ranging from 0.16 to 1.20 kcal.min-1.degree C-1.m-2. Due to the negligible thermal gradient across the skin layer, however, this would be of little physiologic significance. Assumptions concerning the homogeneity of skin thickness across gender and measurement site when investigating thermal insulation of the peripheral tissues would not, therefore, influence the reported results significantly. However, it has recently been shown that the calculated lipid fraction of the adipose tissue layer varies according to a person's level of adiposity. Using a two-component model of adipose tissue, the predicted thermal conductivity (k) of the adipose tissue in the present sample was found to range from 0.50 to 0.97 x 10(-3) kcal/(cm.s-1.degree C-1), being significantly lower (P = 0.005) in the five most obese cadavers [6.66 +/- 0.45 x 10(-4) kcal/(cm.s-1.degree C-1)] than in the five most lean cadavers [8.22 +/- 0.93 x 10(-4) kcal/(cm.s-1.degree C-1)]. Adiposity level correlated significantly (r = 0.80; P < 0.01) with calculated k values, suggesting caution must be taken when assuming a single k for the adipose tissue layer when examining divergent populations (i.e., obese vs. thin). PMID- 8000284 TI - Application of a valveless anesthesia circuit for deep diving. AB - The Mapleson E breathing circuit used in anesthesia has no valves or CO2 absorbent canisters and thus entails low resistance to breathing and has low requirements for fresh gas flow (FGF). The authors investigated whether these advantages would make a circuit, modified for hyperbaric use, able to support ventilation during heavy work on the surface and at deep depths with reduced FGF rates. The current recommended FGF for free-flowing diving circuits is 170 liters/min. Six Navy divers participated in 10-min graded exercise sequences, peak workload 220 W. Measurements were made of inspired and end-tidal concentrations of CO2, tidal volume, respiratory rate, and CO2 production at both sea level and 2.7 MPa dry environment. At sea level, all six divers were able to finish their exercises using the modified circuit with all tested rates of FGF. At 2.7 MPa the exercise sequence could be finished by all subjects when FGF was 170 liter/min and by five subjects when FGF was 127.5 liter/min, but high end tidal CO2 measurements and hypercapnia symptoms were common at 127.5 liter/min. None of the subjects was able or allowed to finish the exercise sequence when FGF was 85 liter/min. Lower work-loads of 75 and 150 W for up to 4 min were completed easily by all subjects at all three rates of FGF. We conclude that this circuit concept warrants further study because it requires lower FGF than is currently used with open-circuit helmets and is valveless; how much of a reduction in FGF could be tolerated with heavy work at depths such as 2.7 MPa requires further study. PMID- 8000285 TI - High altitude dives in the Nepali Himalaya. AB - British divers undertook no-stop decompression dives at altitudes of 15,700 and 16,000 ft (4,785 and 5,33 m) in the Everest region of the Nepali Himalaya. They performed 23 dives on oxygen and two on nitrox (60% N2:50% O2. The dives took place under ice in two lakes, Gokyo Tsho and Donag Tsho. The maximum depth achieved was 98 feet fresh water (29.32 msw), maximum duration was 39 min in water, 44 min on gas. PMID- 8000286 TI - Does hyperbaric oxygen have a cancer-causing or -promoting effect? A review of the pertinent literature. AB - We reviewed all known published reports or studies related to a possible cancer causing or growth-enhancing effect by hyperbaric oxygen. Published articles were retrieved using Medline searches for the period 1960-1993. Additional references were obtained from bibliographies included in those articles discovered in the computer search. Also, hyperbaric medicine text books and the published proceedings of international hyperbaric conferences were visually searched. Studies and reports discovered in this fashion and related to the topic were included in the review. Twenty-four references were found: 12 were clinical reports, 11 were animal studies, and 1 reported both an animal study and a clinical report. Three clinical reports suggested a positive cancer growth enhancement, whereas 10 clinical reports showed no cancer growth enhancement. Two animal studies suggested a positive cancer-enhancing effect, and 10 animal studies showed no such effect. (The report that included both animals and humans is counted in both groups). The vast majority of published reports show no cancer growth enhancement by HBO exposure. Those studies that do show growth enhancement are refuted by larger subsequent studies, are mixed studies, or are highly anecdotal. A review of published information fails to support a cancer-causing or growth-enhancing effect by HBO. PMID- 8000287 TI - Physician awareness of hyperbaric oxygen in a large tertiary care hospital. PMID- 8000288 TI - Effect of plasma treatment on tribological properties of synthetic ligaments. AB - The objective of this study was to determine the optimal experimental conditions for plasma treatment of polyester ligaments. Two different surface modification techniques were used: tetrafluoroethylene and methane. Gas flow rate, pressure, power, and treatment period giving a thin film with low friction coefficient and low surface energy was determined. Control and plasma treated surfaces were characterized by X-ray photoelectron spectroscopy to investigate the functionalization of the treated surfaces in detail. The surface tension of control and plasma treated surfaces were determined from contact angle measurements to understand the adhesion and reactivity of films with aqueous medium. The results showed a decrease in friction coefficient from 0.45 to 0.28 and from 0.45 to 0.26 for thin films deposited respectively by tetrafluoroethylene (TFE) and methane (CH4) plasma. Contact angles increased from 63 degrees to 120 degrees for TFE plasma and from 63 degrees to 93 degrees for CH4 plasma. Large contact angles mean a weak affinity between molecules in water/material phase, so that the power to attract cells to the surface of the material is too weak. The results showed that optimal film, i.e., low static friction coefficient and large contact angle, can be obtained by a CH4 plasma treatment at high power RF. For TFE plasma treatments, a low power RF is needed to obtain a thin film with a stable chemical structure. PMID- 8000289 TI - Mechanochemical synthesis of bioactive material: effect of environmental conditions on the phase transformation of calcium phosphates during grinding. AB - The effect of environmental conditions on the crystalline transformation of metastable calcium phosphates during grinding was investigated using X-ray diffractometry and fourier transformed infrared spectroscopy. A mixture of CoA and dicalcium phosphate anhydrate (DCPA, CaHPO4) did not transform after grinding in air. On the other hand, CaO and dicalcium phosphate dihydrate (DCPD, CaHPO4 2H2O) were converted into a noncrystalline solid. Mixtures of DCPD and Ca(OH)2 transformed into low-crystallinity hydroxyapatite after grinding in air. When ground under N2, a mixture of Ca(OH)2 and DCPD did not transform into hydroxyapatite, whereas that of DCPD: Ca(OH)2: CaCO3 = 1:0.8: 0.2 did. The results of X-ray diffraction of FT-IR spectra suggested that the presence of carbon dioxide in the grinding system was necessary for transformation from metastable calcium phosphates to hydroxyapatite. PMID- 8000290 TI - Use of enzyme-linked immunosorbent assay (ELISA) for detection and quantification of monoclonal antibodies. AB - The thrust of the present work is the demonstration of the feasibility of using an enzyme-linked immunosorbent assay (ELISA) for the detection and quantification of a monoclonal antibody human serum. The antibodies used, 7E3 and D3GP3, have been proposed as platelet receptor blockers, being directed specifically against the platelet membrane receptors (glycoprotein IIb/IIIa) and thus of significance in the management of patients at a very hgih risk of thrombotic occlusion. It is shown that 7E3 is more easily adsorbed than D3GP3 and hence has a higher potential for the stated application. PMID- 8000291 TI - Reinforcement of bone cement around prostheses by pre-coated wire coil: a preliminary study. AB - The longevity of the cemented total hip joint replacement depends on the integrity of the cement fixation with respect to the interfaces of the metal stem and bone, and stress/strain transmission and its distribution. A simple coil made of stainless steel wires was placed around a tapered stem in a simulated cement mantle to counteract the radial- and hoop-stress and static push-out mechanical tests were performed. The results show statistically significant increases in ultimate strain (+17.62%), ultimate load (+110.34%), stiffness (+117.63%), and fracture toughness (+153.63%) exhibited by the wire reinforcement over the control. Precoating with thin layer of polymethylmethacrylate may also enhance the mechanical properties of the reinforced cement mantle. This simple device may contribute to the longevity of the cement mantle by virtue of the enhanced mechanical properties, which in turn will be able to absorb more energy transmitted through the metal stem. PMID- 8000292 TI - Modelling tissue behaviour based on hyperelasticity theory. AB - The tissues are during their physiological function, e.g., in the course of growth, adolescence, and aging, subjected to a cyclic mechanical loading and to large displacements and rotations as well. A tissue free of all external tractions is in a state that minimizes its internal power. In the course of aging of the tissues, for instance in the wall of the aorta, the vein, and also in the myocardium or heart valves, the decrease of the water content and increase of the collagen content occurs; while in compact and trabecular bone the contents of both mineral substances and collagen, undergo reduction. In accordance with it, the strain energy function and the constitutive equations of living tissue based on the hyperelasticity theory using rotationless strain were studied. On the base of the proposed eigenvalue decomposition of the rotationless strain tensor and hyperelasticity the strain energy function was formulated as depending on biological time of tissue. The quantity of strain energy function per unit of the biological time, which essentially characterizes the velocity of change of mechanical response of tissue in the course of its aging, was also defined. The coefficient of tissue aging is the further diagnostic parameter, which is independent of the rotationless strain tensor and expresses the relative change of mechanical response of tissue during the biological time. The corresponding constitutive equation of tissue depending on the biological time is also determined. On the base of the regression analysis the theoretical stress-strain curves for myocardium and blood vessels were determined. The numerical results reveal that the coefficient of aging progressively increases in hardening tissues (coronary artery, vena cava inferior) whereas at the softening tissues it has a relatively slow increase at the dependence on tissue aging. PMID- 8000293 TI - Fractal dimension analysis of mandibular bones: toward a morphological compatibility of implants. AB - In addition to biological and mechanical compatibilities for promising implant materials, a morphological compatibility is proposed by the authors. It has been reported by many investigators that implant surface with appropriate roughness and pore size exhibit better bone ingrowth activities. However, these parameters cannot characterize the complexity of surface textures. In the present study, dentulous and edentulous mandibular alveolar bones were utilized. Four segments from each mandible were subjected to the Fractal Dimension (DF) analysis. It was found that the dentulous mandible showed the DF of 1.81 +/- 0.03 while the edentulous mandible exhibited DF of 1.55 +/- 0.07, indicating that the former has more complex surface texture. It was also found that there could be a linear relationship between the surface roughness and the fractal dimension. PMID- 8000294 TI - Risk factors for childhood acute non-lymphocytic leukemia: an association with maternal alcohol consumption during pregnancy? AB - A population-based case-control study of acute non-lymphocytic leukemia (ANLL) was performed with 80 ANLL cases diagnosed between 1973 and 1979, who were derived from the nationwide register of the Dutch Childhood Leukemia Study Group. Cases were compared to three age- and sex-matched population controls and, in order to control for recall bias, to 517 cases with acute lymphocytic leukemia from the same study base. Information on a large number of exposures to putative risk factors was collected by a self-administered questionnaire mailed to the parents. No significant association of ANLL was observed with smoking habits of the mother during pregnancy, ultrasound examinations, prenatal exposure to x rays, viral infections, or hydrocarbon exposure. When comparing ANLL cases to population controls, maternal use of alcohol during pregnancy was associated with a more than two-fold increased risk of ANLL (odds ratio = 2.6; 95% confidence interval = 1.4-4.6). A similar increase in risk was found when comparing ANLL cases to acute lymphocytic leukemia cases. There was no significant elevation in risk for ANLL found for parental use of alcohol 1 year before pregnancy. This study suggests that intrauterine exposure to alcohol may increase the risk for childhood ANLL. PMID- 8000295 TI - Familial predisposition to precancerous gastric lesions in a high-risk area of China. AB - Aggregation of intestinal metaplasia and dysplasia was investigated among families participating in a population-based gastroscopic screening survey in an area of China with one of the world's highest rates of stomach cancer. The prevalence of gastric dysplasia was significantly increased among those with dysplasia among siblings or spouses, but not parents. The odds of dysplasia were nearly doubled if an eldest brother or a spouse was affected. Sibling and spousal associations for intestinal metaplasia were much less pronounced and not statistically significant. The specificity of the findings suggests that familial risk of advanced precancerous lesions (dysplasia) is influenced not only by genetic factors, but also by environmental factors operating in childhood and early adult life. PMID- 8000296 TI - Prediagnostic serum selenium and zinc levels and subsequent risk of lung and stomach cancer in Japan. AB - Serum samples were collected in Hiroshima and Nagasaki, Japan, from 1970 to 1972 for 208 persons who in 1973-1983 developed stomach cancer; for 77 who in 1973 1983 developed lung cancer; and for controls matched for age, sex, city, and season of blood collection. Average serum levels of selenium and zinc were slightly (< 5%) but not significantly lower among the cancer cases than among controls. Smoking-adjusted risks of lung cancer were elevated only among those in the lowest quartiles of serum selenium [odds ratio (OR) = 1.8] and zinc (OR = 1.3); the trends in risk of this cancer with decreasing serum levels were neither linear nor significant. Little or no excess risk of stomach cancer was observed among those with lowest levels of selenium (OR = 1.0) or zinc (OR = 1.2). These exploratory findings add to limited data available from other reports showing slightly increased risks of lung cancer associated with low blood levels of selenium, but suggest little association with either lung or stomach cancer across normal selenium or zinc ranges in this Japanese population. PMID- 8000297 TI - Inherited glutathione-S-transferase deficiency is a risk factor for pulmonary asbestosis. AB - Pulmonary diseases attributable to asbestos exposure constitute a significant public health burden, yet few studies have investigated potential genetic determinants of susceptibility to asbestos-related diseases. The glutathione-S transferases are a family of conjugating enzymes that both catalyze the detoxification of a variety of potentially cytotoxic electrophilic agents and act in the generation of sulfadipeptide leukotriene inflammatory mediators. The gene encoding glutathione-S-transferase class mu (GSTM-1) is polymorphic; approximately 50% of Caucasian individuals have a homozygous deletion of this gene and do not produce functional enzyme. Glutathione-S-transferase mu (GST-mu) deficiency has been previously reported to be associated with smoking-induced lung cancer. We conducted a cross-sectional study to examine the prevalence of the homozygous deletion for the GSTM-1 gene in members of the carpentry trade occupationally exposed to asbestos. Members of the United Brotherhood of Carpenters and Joiners of America attending their 1991 National Union conference were invited to participate. Each participant was offered a chest X-ray and was asked to complete a comprehensive questionnaire and have their blood drawn. All radiographs were assessed for the presence of pneumoconiosis in a blinded fashion by a National Institute for Occupational Safety and Health-certified International Labor Office "B" reader. Individual GSTM-1 status was determined using polymerase chain reaction methods. Six hundred fifty-eight workers were studied. Of these, 80 (12.2%) had X-ray abnormalities associated with asbestos exposure. Individuals genetically deficient in GST-mu were significantly more likely to have radiographic evidence of nonmalignant asbestos-related disease than those who were not deficient (chi 2 = 5.0; P < 0.03).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8000298 TI - DQA1 and DQB1 genes in patients with squamous cell carcinoma of the cervix: relationship to human papillomavirus infection and prognosis. AB - Women carrying serological HLA-DQ3 specificity have previously been found to have an increased risk of developing squamous cell carcinoma of the cervix. Here we report the distribution of DQA1 and DQB1 genes in 158 Norwegian patients with squamous cell carcinoma of the cervix and in 186 ethnically matched controls. The DQA1 typing revealed an increase of the DQA1*030X allele among the patients compared to the controls [odds ratio (OR) = 1.77] and a decreased frequency of DQA1*0201 among the patients (OR = 0.57). DQB1*0301 was increased (OR = 1.81) and DQB1*0201 was decreased (OR = 0.64) among the patients compared to the controls. Among the patients, 67% carried genes encoding DQ3 (DQB1*0301, DQB1*0302, or DQB1*0303) compared to 51% of the controls, which gives an odds ratio of 2.0, significant both in corrected and uncorrected statistical analysis. The haplotype DQA1*0201-DQB1*0201 was decreased among the patients compared to the controls (OR = 0.38). Human papillomavirus (HPV) has been demonstrated to be a contributing factor in the development of this carcinoma. Primary tumors (fresh frozen) from 65 of the patients were analyzed for the presence of HPV 16 and HPV 18 by polymerase chain reaction. The DQA1-DQB1 haplotypes were distributed randomly among the patients with HPV 16 or HPV 18 present in their tumors so no association was found. Neither was there any difference between DQ3-positive and DQ3-negative patients in the frequency of HPV 16- or HPV 18-positive tumors. DQB1*03 showed no independent significant association with relapse-free survival.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8000299 TI - Identification and quantification of the N-acetylcysteine conjugate of allyl isothiocyanate in human urine after ingestion of mustard. AB - Allyl isothiocyanate (AITC) is a constituent of cruciferous vegetables. It occurs widely in the human diet as a natural ingredient or food additive. AITC possesses numerous biochemical and physiological activities. It is cytotoxic and tumorigenic at high doses and also is a modulator of enzymes involved in metabolism of xenobiotics, including carcinogens. It is plausible that the wide consumption of dietary AITC may have profound effects on human health. To facilitate investigations of the effects of dietary AITC in humans, a method of measuring its uptake is needed. In this study, a urinary marker was developed for quantifying AITC uptake in humans. Four adult volunteers were asked to eat a meal containing brown mustard as the source of AITC. The 48-h urine samples were collected from these individuals and analyzed by reverse phase high performance liquid chromatography. A major urinary metabolite was found, which was identified as N-acetyl-S-(N-allylthiocarbamoyl)-L-cysteine, the N-acetylcysteine conjugate of AITC, by comparing its retention time and UV, nuclear magnetic resonance, and mass spectra with those of the synthetic standard. After ingestion of mustard, the AITC conjugate was detected in urine collected from 0 to 12 h. No conjugate was found in urine samples collected after 12 h. The major portion of this metabolite was excreted within 8 h. The average total excretion of AITC conjugate was 5.4 +/- 1.7 (SD) mg after consumption of 10 g of mustard and 12.8 +/- 2.0 mg when 20 g of mustard was consumed. Thus, a dose-dependent excretion of this metabolite was demonstrated.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8000300 TI - Plasma carotenoids as biomarkers of vegetable and fruit intake. AB - Higher intakes of vegetables and fruits are associated with a lower risk of certain human cancers. A biomarker of vegetable and fruit intake would be a valuable research tool. A cross-sectional study assessed the association between plasma carotenoid concentrations and intakes of vegetables and fruits. Plasma carotenoids (alpha-carotene, beta-carotene, lutein, beta-cryptoxanthin, and lycopene) were measured in 50 male and 49 female participants, aged 18-37 years, with a wide range of habitual vegetable and fruit intakes. Dietary intakes were assessed via a food frequency questionnaire. Intake of vegetables and fruits and high carotenoid foods were measured. The sum of the plasma carotenoids (excluding lycopene) was highly correlated with intake of total vegetables and fruits (r = 0.59). Of the individual plasma carotenoids, plasma alpha-carotene had the highest correlation with intakes of both total vegetables (r = 0.50) and total fruits (r = 0.58). Intakes of foods with high carotenoid contents were correlated with their corresponding plasma concentrations as follows: high beta-carotene foods (r = 0.41); high lutein foods (r = 0.46); and high lycopene foods (r = 0.11). Multiple regression analyses showed that intake of total vegetables and fruits was the most significant determinant of each plasma carotenoid except lycopene. The utility of combining the plasma carotenoids as biomarkers of vegetable and fruit intake was assessed by a stepwise regression of total vegetable and fruit intake on plasma carotenoids. Significant determinants of intake of total vegetables and fruits were alpha-carotene, beta-cryptoxanthin, lutein, and energy intake (R2 = 0.53).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8000301 TI - beta-Carotene supplementation results in an increased serum and colonic mucosal concentration of beta-carotene and a decrease in alpha-tocopherol concentration in patients with colonic neoplasia. AB - The aim of this study was to evaluate the colonic mucosal beta-carotene (BC) concentration following supplementation with BC and to determine if an increase in BC concentration influences vitamin E (alpha-tocopherol) status. The concentration of BC and alpha-tocopherol was assessed in serum and colonic tissue obtained from subjects with a history of colonic polyps or resected cancer (Dukes A, B1, or B2). Serum and mucosal biopsy samples were obtained prior to and following 3 months daily p.o. supplementation with 30 mg of BC or placebo. The concentration of BC was significantly increased in serum and colonic mucosa from both polyp and cancer subjects following supplementation as compared to presupplementation values and values from subjects receiving a placebo. The concentration of alpha-tocopherol in serum from cancer subjects was significantly decreased in samples obtained at the end of 3 months of BC supplementation as compared to placebo-matched controls. In BC-supplemented polyp subjects the tissue concentration of alpha-tocopherol was also significantly decreased relative to presupplementation values. The results indicate that BC supplementation does result in a significant accumulation of BC in the colonic mucosa but that the alpha-tocopherol concentration in both serum and colonic tissue may be compromised by an increased intake of BC. The mechanism for the decrease in alpha-tocopherol in conjunction with the increase in BC will require further study in order to develop strategies which will prevent vitamin E deficiency in BC-supplemented individuals. PMID- 8000302 TI - Factors affecting plasma retinol decline during long-term administration of the synthetic retinoid fenretinide in breast cancer patients. AB - Administration of the synthetic retinoid Fenretinide lowers circulating retinol and may thus affect night vision. We have recently shown that plasma retinol levels below 100 ng/ml are associated with moderate alterations of the dark adaptometry test. To identify which patients are more likely to experience a decrease of plasma retinol under this threshold, we measured plasma levels of retinol, Fenretinide, and its metabolite 4-MPR in a cohort of 28 women receiving Fenretinide at the daily dose of 200 mg and studied their relationship with clinical characteristics such as age, menstrual status, body mass index, and time on treatment. Our results show that patients aged over 55 years with a higher percentage of adipose tissue had higher plasma concentrations of 4-MPR, which turned out to be the major determinant of the retinol decrease. This subgroup may thus deserve careful ophthalmological surveillance. PMID- 8000303 TI - Genetics of CYP1A1: coamplification of specific alleles by polymerase chain reaction and association with breast cancer. AB - CYP1A1 is a gene of the cytochrome P-450 family that has been proposed to be a biomarker of cancer risk. We introduce a polymerase chain reaction-based assay to measure allelic variability in exon 7 of the CYP1A1 gene. This genetic variant is associated with an amino acid change at residue 462 in the aryl hydrocarbon hydroxylase protein product. Previously, measurement of CYP1A1 genotypes at this variant site required two assays, one to detect each allele. By using three primers in a single polymerase chain reaction rather than two primers in each of two polymerase chain reactions, the proposed assay may facilitate population based study protocols. We estimate the frequency of this polymorphism in a Caucasian population to be 0.03, with an observed heterozygosity of 0.06. We have also confirmed the Mendelian segregation of this polymorphism in four multigeneration Centre d'Etude du Polymorphisme Humain families and have placed this locus in a multilocus linkage map on chromosome 15q. The distribution of this polymorphism was the same in breast cancer cases as in two sets of healthy controls. PMID- 8000304 TI - Analysis of cytochrome P450 2E1 genetic polymorphisms in relation to human lung cancer. AB - Human cancer risk assessment using molecular genetic techniques is a rapidly emerging field. Many studies suggest that both inherited and acquired genetic predispositions play an important role in carcinogenesis. Cytochrome P450 (CYP) 2E1 is involved in the metabolic activation of N-nitrosamines and other low molecular weight compounds. A recently described genetic polymorphism of CYP2E1 [DraI restriction fragment length polymorphism (RFLP)] has been associated with an increased risk of lung cancer in Japanese. We have assessed the allelic frequency of three RFLPs (PstI, RsaI, and DraI) in African-Americans (n = 109), Caucasian Americans (n = 153), and octogenarian Japanese (n = 42), and also in a United States case-control study of lung cancer (histologically confirmed lung cancer, n = 58; controls, n = 56; total, n = 114). The relationship of the CYP2E1 DraI polymorphism to other CYP2E1 polymorphisms (PstI and RsaI RFLP) was examined. The allelic frequency of the DraI C minor allele for all subjects was 0.09 in Caucasians, 0.09 in African-Americans, and 0.31 in Japanese. In the case control study of lung cancer, no association of the CYP2E1 DraI genotype with lung cancer was found (odds ratio, 1.57; 95% confidence interval, 0.59-4.18). Comparison after discordant CYP2E1 genotypes suggests the presence of different haplotypes in Americans and Japanese. These results indicate that the CYP2E1 DraI RFLP is probably not a cancer risk factor in United States Caucasian or African Americans, although statistical power is limited given the low frequency of the CYP2E1 DraI C minor alleles. PMID- 8000305 TI - Correspondence re: G-S. Qian, et al., A follow-up study of urinary markers of aflatoxin exposure and liver cancer risk in Shanghai, People's Republic of China. Cancer Epidemiol., Biomarkers & Prev., 3:3-10, 1994, and C.C. Harris, Solving the viral-chemical puzzle of human liver carcinogenesis. Cancer Epidemiol., Biomarkers & Prev., 3:1-2, 1994. PMID- 8000306 TI - Hermann Druckrey. PMID- 8000307 TI - Physical activity and colon cancer. AB - Heart disease and cancer, the major causes of mortality and morbidity in Western countries, have common risk factors. Exercise appears to reduce the risk of cardiovascular disease, but its role with respect to primary prevention of cancer has not been emphasized. Here we evaluate the epidemiological studies dealing with exercise and colon cancer. Despite the fact that different methods of assessing the amount of typical exercise of individuals and the different types of physical activity measured (occupational and recreational), there is remarkably consistent evidence that people who are highly physically active could be at a reduced risk of cancer of the colon. An analysis of case-control and cohort studies suggests that exercise might reduce the risk, at least in men, by up to one-third. We conclude that exercise has been overlooked as a potentially useful, effective, and acceptable method for reducing the risk of colon cancer. PMID- 8000308 TI - Comparative analysis of results of guaiac and immunochemical tests for faecal occult blood in colorectal cancer screening in two oncological institutions. AB - The performances of three faecal occult blood tests, rehydrated Hemoccult (HOR), Hemoccult sensa (HOS) and Hemeselect (HSEL) on 3 days were compared in 1,725 subjects consecutively recruited in two oncological institutions in Milan and Florence. Significant differences between the results were evident as far as HOR positivity rates (7.5% vs 4.0%, respectively) and specificity (94.3% vs 97.5%, respectively) are concerned. Overall positivity rates of HOR, HOS and HSEL were 5.9%, 5.4% and 12%, respectively; significant differences were evident between HSEL and each of the two guaiac tests. Cancer was detected in eight subjects, adenoma/s in 47. Specificity estimates were 95.8%, 90.2% and 90.5% for HOR, HOS and HSEL, respectively; significant differences were evident between HSEL and the other two tests. No significant difference between tests was evident for sensitivity or positive predictive values for cancer or adenomas. In the CSPO (Florence) population (1,223 subjects; five with cancer, 16 with adenoma/s) the performances of 1-day HSEL testing were determined on the basis of the first faecal sample only and compared with 3-day HOR, HOS and HSEL testing. The positivity rates of 1-day HSEL, 3-day HOR, HOS and HSEL testing were 7.0%, 5.0%, 5.5% and 12.9%, respectively. Only 3-day HSEL positivity rate was significantly higher than 1-day HSEL. One-day HSEL specificity (94.9%) was significantly higher than 3-day HSEL (90.0%), whereas no significant difference was seen between 1-day HSEL, HOR (96.5%), and HOS (96.1%) specificity. No significant difference between tests is evident in the CSPO population as far as positive predictive values and sensitivity for cancer and adenomas are concerned.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8000309 TI - Assessment of the new immunological test Hemoblot for detecting occult blood in faeces. AB - Hemoblot, a new immunological faecal occult blood test, produced by Gamma, Angleur, Belgium, was characterized and compared with another immunological test (HemeSelect, SmithKline Diagnostics, USA) and with a guaiac test (Hemoccult II, SmithKline Diagnostics). The analytical sensitivity of Hemoblot is 0.15 mg haemoglobin/g faeces and the test is specific for human haemoglobin. In addition, 135 symptomatic patients who had to undergo a colonoscopy were tested using the three tests. Two criteria were considered for the analysis: (1) the blood criterion: any pathology likely to cause colorectal or other bleeding; and (2) the precancerous-cancerous criterion: the pathology being either a colorectal polyp > 0.5 cm or a colorectal cancer. Considering both criteria, the sensitivity of Hemoblot was significantly higher than the sensitivity of Hemoccult: 38% and 23%, respectively, for the blood criterion; and 54% and 29% for the precancerous cancerous criterion. Sensitivity and specificity did not differ statistically between Hemoblot and HemeSelect but Hemoblot was faster and simpler to perform. It could be widely used in mass screening. PMID- 8000310 TI - ECP-EURONUT-Intestinal Metaplasia Study: urinary and gastric juice analyses. AB - In an international multi-centre study of diet and precancerous lesions of the stomach, 24 h urine samples were analysed from 133 sets of patients with intestinal metaplasia (IM) and their matched controls from the UK, 14 sets of cases and controls from Portugal and 22 sets from Poland. In addition, urine aliquots (but not 24 h volumes) were available from 12 matched sets from Greece and 19 from Croatia. There was no difference between cases and controls in the daily urinary excretion (as a measure of daily intake) of sodium or nitrate but the potassium output by patients with IM was significantly lower than that of the controls in the UK and Portugal, and the ratio Na/K was higher in patients with IM than in controls in the UK and Portugal, but not in Poland, Greece or Croatia. Gastric juice samples were analysed from 133 sets of IM patients and endoscoped controls from the UK and 22 sets from Croatia. When compared with the endoscoped controls, IM patients from both countries had a significantly higher proportion of gastric juice samples containing bacteria and nitrite and with a pH > 6. The results are discussed in relation to current hypotheses on gastric carcinogenesis. PMID- 8000311 TI - Lung cancer in Estonia in 1968-87: time trends and public health implications. AB - Changes in lung cancer incidence and mortality in Estonia were studied for 20 years (1968-87). A steady upward trend was observed for men and women. The 1983 87/1968-72 age-standardized incidence rate ratio was 1.22 (95% confidence interval (CI) 1.15-1.29) in men and 1.34 (95% CI 1.16-1.54) in women. The corresponding mortality rate ratio was 1.26 (95% CI 1.18-1.34) in men and 1.35 (95% CI 1.16-1.57) in women. The age-specific incidence and mortality rates increased clearly towards the younger birth cohorts. For men and women, the increase was most evident for the age group 45-64 years. In women there was a more rapid increase in incidence and mortality than in men. It may be a result of a substantial increase of tobacco smoking, particularly among women, after the World War II. The high and still rising occurrence of lung cancer is closely related to the high prevalence of smoking; in addition, high tar yields in domestic cigarettes could have been responsible for an elevated lung cancer risk during the past decades. There is not tobacco control programme in Estonia, and existing legislation and regulations do not defend the non-smoking population. PMID- 8000312 TI - Smoking, alcohol consumption and the risk of cancer of the biliary tract; a population-based case-control study in The Netherlands. AB - Although cancer of the biliary tract is a highly fatal disease, the relationship with modifiable, life style-related factors is hardly studied. Between 1984 and 1987 we conducted a case-control study of 114 patients and 487 controls from the general population. An interviewer-administered questionnaire was used to collect information on life-time smoking habits and life-time alcohol consumption. The information was obtained either from the subjects themselves (direct response) of from relatives (indirect response). Results show that neither smoking at the time of interview (odds ratio (OR) 1.5; 95% confidence interval (CI) 0.9-2.4) nor smoking 2, 5 or 10 years before were associated significantly with the cancer. Alcohol consumption at the time of interview (OR 1.0; 95% CI 0.6-1.5) or drinking 2, 5 or 10 years before were not significantly associated either. Among current alcohol drinkers, long-term consumers had a reduced risk (duration of use > 38 years vs < 25 years: OR 0.4; 95% CI 0.1-0.9) and late starters an elevated risk (starting age > 38 years vs < 21 years: OR 2.7, 95% CI 1.0-7.5). A modifying effect of alcohol consumption on the smoking-cancer relationship was observed: the risk for current smokers was increased only when they did not drink alcohol at that point in time (OR 3.4, 95% CI 1.3-8.5). Our results indicate that long term moderate alcohol use might be protective against cancer of the biliary tract, whereas smoking might be a risk factor for this cancer. PMID- 8000313 TI - Cell uptake and DNA adduct formation of the 2-amino-3 methyl-imidazo (4,5-f) quinoline in human enterocytes and chick embryo liver cells. AB - The compound 2-amino-3-methyl-imidazo(4,5-f)quinoline (IQ) is a powerful mutagenic compound that can induce tumours in different rat and murine target organs (liver, forestomach and small and large bowel). The ability of mutagenic IQ to form adducts to human embryonic enterocyte DNA (intestine 407 cell lines ATCC) has been studied, considering the DNA extracted from the cells and DNA of the in vitro-cultured cells. The activation with the rat hepatic microsomial fraction S9 plays an important role not only in DNA binding, but also in the uptake of IQ by the enterocytes. In the presence of S9 mix, the DNA adduct formation increases with the incubation time; in the absence of metabolic activation, the binding does not occur. Parallel experiments were carried out for comparison on chick embryo hepatocytes; for these cells, the metabolic activation with S9 mix is not as critical as for enterocytes in IQ uptake and DNA binding. PMID- 8000314 TI - Estimating the level of knowledge of Greek students on cancer aetiology and ways of prevention. AB - The aim of the present research was to establish the perception of the relative importance of various environmental risk factors for cancer among Greek students. A questionnaire was used to assess the students' knowledge on cancer causation. The factors examined included smoking habits, drinking, geophysical factors, pollution, dietary factors, and the students' awareness of the contribution of these factors to the generation of the disease. In addition, we examined the students' attitude to the factors as cancer risk determinants. A random sample of 1,136 students was selected from the matriculated students of various departments of the Aristotelian University of Thessaloniki. We found a relative important lack of knowledge on subjects related to the generation of the disease. PMID- 8000315 TI - Research frontiers in nutrition. Newcastle, UK, 21 April 1994. PMID- 8000316 TI - Delivering services to the rural elderly: a study of policy implementation. AB - This article presents an analysis of two demonstration projects designed to improve delivery of services to elderly residents of rural Nebraska. One project employs a statewide system of care management focused on individual clients. In the other, local agencies in four communities coordinate services by using the local senior center as a focal point. This article uses established theory of policy implementation to illustrate problems encountered in starting new social programs that require state-local cooperation. Four guidelines are suggested for policymakers: (a) if local agencies are responsible for implementation, local managers must be involved in all the planning activities for new programs; (b) clear guidelines are needed to be sure that there is consensus concerning the details of implementation; (c) all health care providers should be involved in implementation when health care services are being coordinated; and (d) community coordinating councils can be effective. PMID- 8000317 TI - Long-term care: what reforms are on the horizon? PMID- 8000318 TI - Evaluating a case management service: a family perspective. AB - This article describes how a long-standing community-based case management service conducted a survey of clients and their family members. The overall objectives of the survey were twofold: to learn how best to undertake such a survey and to get feedback from service users about the strengths and limitations of the service with suggestions for improvement. A steering committee was established, comprising key stakeholders of the service: consumers, family members, case managers, and other service providers. Steering Committee members were actively involved in shaping the questions, designing the instruments, conducting parts of the survey, and preparing the report and recommendations for the board of directors. This article reports on the process of the survey, the findings of the survey of family members, and service modifications that were introduced as a result of family members' feedback. The benefits and significance of actively involving family members throughout the survey are discussed. PMID- 8000319 TI - The social networks of seriously mentally ill persons receiving case management services. AB - Social network characteristics, or the patterning of one's social ties, are an important indicator of social support for persons with serious mental illness. Yet relatively few studies have been done on the particular network characteristics of clients receiving case management services in community settings. An understanding of the range of potential and actual social network contacts for persons with serious mental illness is important for targeting interventions to enhance their community supports. In this study, 125 clients of two urban community treatment teams were surveyed by case managers to determine their overall social network size, personal or support network size, and participation in any of 11 network clusters. Results of the study are presented with implications for the social functioning of persons with serious mental illness and suggestions for case manager interventions toward network expansion. PMID- 8000320 TI - Case managers discuss ethics: dilemmas of an emerging occupation in long-term care in the United States. AB - As case management programs mature, ethical questions undoubtedly arise. Yet there are few, if any, standards by which case managers can guide their actions and decisions. In this article, the authors present the results of a survey of 251 frontline case managers in 10 states who were asked to describe the ethical challenges they face. The respondents were conscious of struggling with difficult, even life-and-death decisions involving important choices in their clients' lives. Generally, the case managers were committed to the ideology of respect for client autonomy but found themselves making uneasy compromises with the concept at every turn. Ethical issues arose not only with the client but also with the client's family, colleagues, and providers. Case managers, long-term care providers, and governmental policymakers could all benefit from both theoretical and practical explorations of desirable approaches to individual and societal long-term care decisions. PMID- 8000321 TI - Satisfaction and role performance of case managers in the mental health system. AB - The demand for case managers in the mental health system has increased as helping persons with severe mental disorders to live in community settings of their choice has become a primary outcome goal of intervention. This article reports on an exploratory study that addressed the following questions: What is the case manager's perception of his or her current work satisfaction, and what factors contribute to this perception? How do case managers perceive their overall sense of well-being, use of social support, and role performance? Is there a difference in the intensive case manager's perception of work satisfaction, general well being, and use of social supports when compared to that of traditional case managers? PMID- 8000322 TI - In pursuit of case management guidelines. PMID- 8000323 TI - Nurse case management: collaborative beyond the hospital walls. AB - In 1989, St. Joseph Medical Center initiated a community-based nursing case management program with two nurses providing care to high-risk, chronically ill, frail elderly patients. This program has expanded to five registered nurses actively following over 120 patients. Target populations now served have expanded to include: frail elderly, high-risk pregnant women, premature infants, AIDS patients, and those with chronic physical and mental illness. The nurse manages and coordinates the care for patients through all settings (community and hospital), brokering services, acting as a patient advocate, and giving traditional hands-on care as needed. Outcomes analysis has shown that, after nursing case management intervention, the patients demonstrated a 71% decrease in admissions to the medical center, a 21% decrease in length of stay, and a 64% decrease in Emergency Room usage. Nursing case management helps to prevent patients' health problems from becoming more complex. Consequently, managing their health effectively requires fewer, less costly resources while achieving improved patient outcomes. PMID- 8000324 TI - The central role of case managers in early discharge planning for hospitalized persons with AIDS. AB - Case managers can play a pivotal role in the hospital discharge planning process for medically complex patients. This is particularly true for persons with AIDS. This prospective study quantifies the importance of this role by examining the ability of case managers, nurses, and physicians to predict (at the time of admission) whether hospitalized AIDS patients would be appropriate for transfer to long-term care facilities after their hospital stays. We studied 120 AIDS patients and their primary providers; 38 (32%) patients were found to be appropriate for discharge to long-term care facilities at the end of their hospital stays. Physicians and nurses had similar accuracy in predicting eventual appropriateness for long-term care (75% and 73% correct, respectively); however, case managers were far more accurate than the physicians and nurses (93% correct, p < .05). This finding highlights the unique ability of case managers to facilitate discharge planning early on in the hospital stays of these complex patients. In this study, case managers were more accurate than physicians or nurses in predicting appropriateness for long-term care of hospitalized persons with AIDS. Case managers should play an integral role in coordinating discharge planning of persons with AIDS; this planning should be part of the hospital admission process. PMID- 8000325 TI - A role for case managers in the physician office. AB - Independent primary care physicians continue to be important gatekeepers for health care services needed by older patients. There is a natural role for case management in the physician office as a link to nonmedical support services that can help the elderly maintain their independence. In this article, the authors describe a model partnership between primary care physicians and a community-wide case management program that was developed to enhance the continuum of care and improve integration of service systems. Rapid response for assessments, brief interventions, and linkage to home and community services are provided through a case manager/liaison who is on-call to physician offices. Patients are seen in the physician office or in their homes or contacted by telephone. The liaison assesses and provides immediate information and referral, maintains short-term contact, or refers patients with complex situations or long-term case management needs to agency or community case management programs. The liaison also makes regular office rounds to maintain visibility, discuss cases, and educate staff about patient risk factors. Physicians and patients have been pleased with the model. PMID- 8000326 TI - Tying it all together: integrating a hospital-based health care system through case management education. AB - Recognizing the importance of the case manager as a system integrator, United Health Services, Inc. (UHS), a hospital-based health care system located in upstate New York, implemented several diverse case management models. Case managers were working in a variety of settings, often in isolation. It was determined that a system-wide case management education program would accomplish two goals: (a) provide all case managers within the UHS system with similar case management practice skills and language, and (b) provide an opportunity for case managers to meet, share role responsibilities and common case management issues, and use each other as resources. With input from leadership throughout the UHS system, a 4-week case management education program was developed and presented. Participants included multidisciplinary staff who had case management responsibilities within the system. Sessions were taught by UHS staff experts in a number of different disciplines. A teaching guide and manual were developed to supplement the didactic material. Feedback from the program was provided via written participant evaluation and follow-up discussions. PMID- 8000328 TI - Managed care for long-term care claim success. PMID- 8000327 TI - Determinants of client termination in hospital-based case management programs. AB - Increasing attention is being focused on hospital-based programs that address the needs of the frail elderly. This article reports results from a demonstration of hospital-based case management (HBCC). Baseline, 3-, 6-, and 12-month assessment data are analyzed to determine why clients terminated from HBCC programs. Subsamples of community- and hospital-originated clients are examined to determine what factors predict case management termination. About half of both hospital- and community-originated clients left case management within 12 months because of death, nursing home placement, referral to another case management agency, relocation out of the service area, or discharge as self-sufficient. Hospital-originated clients were more likely to die within the first 6 months after entering case management than were community-originated clients. Cognitive and functional abilities were important predictors of termination status. PMID- 8000329 TI - The xylan-degrading enzyme system. PMID- 8000330 TI - Inhibitory effect of cadmium acetate on synaptosomal ATP diphosphohydrolase (EC 3.6.1.5; apyrase) from adult rat cerebral cortex. AB - ATP diphosphohydrolase (EC 3.6.1.5; apyrase) is an enzyme that can promote ATP and ADP hydrolysis to AMP plus inorganic phosphate and depends on divalent cations such as Ca2+ or Mg2+. In previous papers we described this enzyme in the synaptosomal fraction from the central and peripheral nervous system. The present report examines whether cadmium acetate could affect the in vitro activity of the enzyme in the synaptosomal fraction from the cerebral cortex of adult male Wistar rats. Cadmium (Cd2+), a heavy metal with neurotoxic effects, inhibited the enzyme in a concentration-dependent manner. All concentrations tested (0.05-1.0 mM) significantly inhibited the hydrolysis of both substrates (ATP and ADP), with the exception of 0.05 mM on ATP hydrolysis. The kinetic data indicate a noncompetitive inhibition between the cations Cd2+ and Ca2+. PMID- 8000331 TI - Location and rapid analysis of the intragenic BamHI polymorphic site of the factor IX gene. AB - We report the precise location and a polymerase chain reaction (PCR)-based method for the analysis of the intragenic BamHI polymorphism of the factor IX (FIX) gene. After screening DNA samples from the Brazilian Black population by a selective amplification of a segment of the FIX gene containing entire exon 2, intron 2, and exon 3 followed by digestion of PCR products with BamHI, we were able to identify individuals presenting the polymorphic BamHI site. By DNA sequencing of selected samples, the dimorphic base was located at nucleotide number 6575 (intron 2). The PCR method outlined here allows rapid and easy analysis of this polymorphism. Its application may be particularly useful for carrier detection and prenatal diagnosis of hemophilia B in the Black population, thus far the only one that has been shown to be polymorphic for this site. Because of its apparent restrictive pattern it may also be used in combination with other markers for estimates of racial admixture in mixed populations in which the Black population is present (as is the case for most countries in the American continent). PMID- 8000332 TI - Activity of synaptosomal ATP diphosphohydrolase from hippocampus of rats tolerant to forebrain ischemia. AB - Cerebral ischemia causes cell death of vulnerable neurons in mammalian brain. Wistar adult rats (male and female, weighing 180-280 g) were submitted to 2 min, 10 min, or to 2 and 10 min (separated by a 24-h interval) of transient forebrain ischemia by the four-vessel occlusion method. Animals subjected to the longer ischemic episodes had massive necrosis of pyramidal CA1 cells of the hippocampus, while animals receiving double ischemia (2 + 10 min) showed neuronal tolerance to the ischemic insult. ATP-diphosphohydrolase activity from hippocampal synaptosomes was assayed in these three groups (N = 6 animals/group) under two conditions: no reperfusion and 5-min of reperfusion. The control values for ATPase and ADPase activities were 144.7 +/- 18.8 and 60.6 +/- 5.24 nmol Pi min-1 mg protein-1, respectively. The 10-min group without reperfusion showed an enhancement of approximately 20% for ATPase and ADPase activities. In reperfused rats, only the 2-min group had a 20% increase in both enzymatic activities. We suggest that modulation of ATP-diphosphohydrolase activity might be involved in molecular events that follow both ischemia and reperfusion. PMID- 8000333 TI - Effect of carbon source and extracellular pH on the acidification of the culture medium and phosphatase excretion in Neurospora crassa. AB - Exogenous Ca2+ at concentrations up to 3.5 mM increases the sucrose-induced acidification of the culture medium when the mold Neurospora crassa is grown on low-phosphate (Pi) medium at pH 7.8. Induction depends on the pH of the culture medium adjusted for conidial inoculation and on the absence of carbon sources generating cytoplasmic acetyl CoA. Furthermore, the excretion of Pi-repressible acid and alkaline phosphatases was not stimulated by increasing exogenous Ca2+ levels. We also provide evidence that the extracellular pH monitoring by Neurospora crassa may be a determinant in the selective excretion of Pi repressible acid and alkaline phosphatases. PMID- 8000334 TI - Lipophorin as a lipid carrier in the hemolymph of the horseshoe crab, Limulus polyphemus. AB - A high-density lipoprotein (HDL) was obtained from the hemolymph of Limulus polyphemus in yields generally less than 30 micrograms/ml by ultracentrifugal flotation. SDS-PAGE revealed two apolipoproteins with masses similar to those of apolipophorins (apoLp-I, 265 +/- 14 kDa; apoLp-II, 89 +/- 6 kDa). Lipid composition was different from both insect lipophorin and crustacean HDL, and showed less diacylglycerols than triacylglycerols (3.8% and 36.2% of total lipids, respectively). Since Limulus polyphemus is closely related to precambrian chelicerates, our results confirm that lipophorin was present early in the evolution of arthropods. PMID- 8000335 TI - Hemagglutinating and sialidase activities of subpopulations of influenza A viruses. AB - The present study was conducted to investigate the characteristics of two samples of influenza A/England/42/72 (H3N2) virus, one of them selected by an adsorption elution technique, to determine the possible existence of virus variants or subpopulations. Based on specificity of virulence-related cell receptor-binding and sialidase activities, this selection technique using human O group erythrocytes revealed the presence of variants within a standard virus sample with diversity for their hemagglutinating and sialidase activities. The standard like (E1) sample exhibited titers of 4 and 32 HAU (hemagglutinating units in 25 microliters) with human O group and chicken erythrocytes, respectively, while the sample obtained by the adsorption-elution process (E2) exhibited titers of 32 and 4 HAU, respectively, with these same types of erythrocytes. The E2 sample showed higher sialidase activity at pH values between 5.4 and 6.6 with human erythrocytes (128-256 HAU), but the E1 sample did not exhibit significant sialidase activity with either human or chicken erythrocytes. The different pH optima for hemolysis (5.2) and sialidase (5.4-6.6) activities and the higher hemolysis indexes present in samples with sialidase activity inhibited by heating (at 56 degrees C for 30 min) or by treatment with EDTA (dilution in buffer containing 2 mM EDTA, a chelating agent on calcium-dependent sialidase activity) demonstrate the independence of these activities in the selected sample: native E2 (absorbance = 0.18), EDTA-treated native E2 (absorbance = 0.28), heated E2 (absorbance = 0.26), EDTA-treated heated E2 (absorbance = 0.41).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8000337 TI - Cytomorphology and immunocytochemistry in the diagnosis of non-Hodgkin lymphomas. AB - 1. Lymph node aspirates from 17 patients with an initial cytologic diagnosis of lymphoma (11 cases) or with suspected lymphoma (6 cases) were studied by immunocytochemistry, which led to a final diagnosis. Immunocytochemical staining demonstrated a B-cell phenotype in 10 cases, one case of anaplastic large cell Ki 1+ lymphoma, one lymphoblastic lymphoma negative for B and T cell markers, one large-cell unclassified lymphoma, and one inconclusive case. Three of the cases with suspected lymphoma were diagnosed as reactive lymphadenitis. 2. Combined cytomorphology and cytochemistry permitted a conclusive diagnosis in 13 out of 14 cases of lymphoma. Histology and immunohistochemistry confirmed the cytologic diagnosis. The inconclusive case was diagnosed as a T pleomorphic, small-cell lymphoma by histology. 3. The accuracy of cytomorphology associated with immunocytochemistry is high. However, the diagnosis of low-grade lymphomas, especially of a T phenotype may be difficult. PMID- 8000336 TI - Hyperandrogenism due to 3 beta-hydroxysteroid dehydrogenase deficiency with accessory adrenocortical tissue: a hormonal and metabolic evaluation. AB - 1. Adrenal ectopic tissue has been detected in the paragonadal region of normal women. In patients with congenital adrenal hyperplasia due to 21-hydroxylase (21 OH) deficiency, the manifestation of hyperplasia of paragonadal accessory adrenal tissue has been usually reported to occur in males. Probably, this is the first report of a female with 3 beta-hydroxysteroid dehydrogenase (3 beta-HSD) deficiency with ectopic adrenal tissue in ovaries. However, the occurrence of hyperplasia of adrenal rests among women with classical congenital adrenal hyperplasia may not be rare, especially among patients with a late diagnosis. 2. We report a woman with 3 beta-HSD deficiency whose definitive diagnosis was made late at 41 years of age immediately before surgery for the removal of a uterine myoma. During surgery, exploration of the abdominal cavity revealed the presence of bilateral accessory adrenal tissue in the ovaries and in the para-aortic region. The patient had extremely high levels of ACTH (137 pmol/l), DHEA (901.0 nmol/l), DHEA-S (55.9 mumol/l), androstenedione (70.2 nmol/l), testosterone (23.0 nmol/l) and 17 alpha-hydroxypregnenolone (234.4 nmol/l) suggesting 3 beta-HSD deficiency. 3. In view of these elevated androgen levels, with an absolute predominance of DHEA and DHEA-S, we evaluated the effect of this hormonal profile on carbohydrate tolerance and insulin response to glucose ingestion. 4. The patient presented normal glucose tolerance but her insulin response was lower than that of 14 normal women (area under the curve, 3 beta-HSD = 17,680 vs 50,034 pmol/l for the control group over a period of 3 h after glucose ingestion).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8000338 TI - Detection of insulin antibodies by radioassay and ELISA: interrelation and correlation with metabolic control in type I diabetes. AB - 1. The literature suggests that the radioassay (RA) and ELISA detect different types of insulin antibodies (IA) (Wilkin et al., 1989. Diabetes, 38: 172-181). 2. In the present study we evaluated the relationship between these two antibodies and their involvement in the metabolic control of Type I diabetic (DMI) patients. 3. IA were measured by RA and ELISA in sera obtained from 34 patients (age: 9-16 years, median = 12.5 years; clinical duration of DMI: 0.1-11.0 years, median = 1.7 years) treated with different types of insulin [purified (bovine + porcine) N = 18, and monocomponent (porcine or human) N = 16] and submitted to various degrees of metabolic control as assessed by glycosylated serum protein (GSP) levels: range, 3.4-13.5%; median = 8.7%; normal value, 0.8-2.4%. 4. Insulin antibody levels measured by RA were: 3264 +/- 300 nU/ml (mean +/- SEM, normal value < 60 nU/ml) and by ELISA: 0.74 +/- 0.11 ELISA index (EI) (normal value, < 0.53). No correlation was found between IA levels measured by RA and ELISA, or between duration of the disease or insulin daily necessity and IA by either method. GSP was positively correlated with IA determined by ELISA (rS = 0.43, P < 0.01) but not with IA determined by RA. 5. The patients on purified bovine + porcine insulin had higher titers of IA by ELISA, compared to those of patients on monocomponent (0.96 +/- 0.15 vs 0.50 +/- 0.13 EI, P < 0.03, while IA levels measured by RA did not differ between groups. 6. These data show that RA or ELISA assays provide different serum titers of IA in insulin-treated diabetics and data obtained with ELISA correlated best with the metabolic control of Type I diabetic patients. PMID- 8000339 TI - Comparative study of two tests of renal diluting ability in Bartter's syndrome. AB - 1. Different results concerning distal NaCl reabsorption have been reported for patients with Bartter's syndrome in tests of renal diluting ability. We describe clearance studies performed on 3 patients with Bartter's syndrome using different routes for body fluid content expansion: water was given orally and 0.45% NaCl solution intravenously. The impact of fluid composition was evaluated in one patient who additionally underwent a "reverse test": i.e., intravenous 5% glucose in water and an oral load of 0.45% NaCl solution. 2. Urine flow per ml glomerular filtration rate (GFR) reached higher levels when the iv route was used (20.6 +/- 1.8 vs 11.8 +/- 5.7%, P < 0.05). Fractional excretion of Na+, Cl- and osmoles increased during NaCl infusion but not during the oral load. Also, distal delivery of solute increased and was greater than that observed in the oral test (21.9 +/- 5.5 vs 11.4 +/- 2.1%, P < 0.05). 3. In contrast, fractional distal chloride reabsorption in the iv test reached subnormal values which were lower than in the oral load test (65.0 +/- 11.2 vs 86.8 +/- 11.0%, P < 0.05). A positive correlation was observed between distal delivery and Cl- fractional excretion (r = 0.87; P < 0.005). In one patient, the 5% glucose infusion resulted in greater urine flow and distal delivery when compared to distilled water or 0.45% NaCl taken orally (28.1 vs 13.3 ml/min and 27.3 vs 12.8%, respectively). These values were as high as those observed during iv administration of hypotonic saline. 4. The iv route was always associated with lower rates of fractional distal chloride reabsorption (70.7 vs 89.1%) regardless of the solute composition and should be recommended when testing the renal diluting ability of patients suspected of Bartter's syndrome. PMID- 8000340 TI - In vitro collagen synthesis by liver connective tissue cells isolated from schistosomal granulomas. AB - Hepatic injury elicits an excessive deposition of extracellular matrix probably due to a loss of control mechanisms in mesenchymal cells in fibrotic lesions, or a local activity of growth factors. To study collagen synthesis in an in vitro model of fibrotic lesions, we isolated liver connective tissue cells (LCTC) from murine schistosomal granulomas in C3H/HeN mice. Collagen was quantified in culture supernatants using a sirius red dye assay. LCTC and skin fibroblasts (SF) secreted similar amounts of collagen per cell and secretion was inversely proportional to the cell density. Cells cultured at low density (10,000 cells/cm2) secreted two- to three-times more collagen per cell when compared to cells grown in high-density cultures (60,000 cells/cm2). Collagen secretion was stimulated by transforming growth factor-beta (TGF-beta) in both cell lines, but the response of LCTC was detected from 1 ng/ml on, while SF responded only to higher concentrations (2.5 and 5 ng/ml). These data do not support the hypothesis that cells from fibrotic livers have lost the normal control mechanisms and suggest that their control is disturbed locally by the presence of peptide growth factors during the development of fibrosis. PMID- 8000341 TI - Characterization of T cell responses to purified leishmania antigens in subjects infected with Leishmania chagasi. AB - T cell responses to lipophosphoglycan-associated protein (LPG-AP) and the rgp63 antigens were studied in subjects with either asymptomatic L. chagasi infection or cured visceral leishmaniasis. The [3H]-thymidine uptake of lymphocytes stimulated with LPG-AP and rgp63 (mean +/- SD) was 14275 +/- 5048 and 3523 +/- 1678 cpm, respectively, for subjects with asymptomatic L. chagasi infection and 20046 +/- 5102 and 5086 +/- 3500 cpm, respectively, for subjects cured of visceral leishmaniasis. The responses to LPG-AP in both asymptomatic and cured visceral leishmaniasis were higher (P < 0.01) than those observed with rpg63. LPG AP induced IFN-gamma production in all subjects studied, while rgp63 did not induce lymphocyte proliferation or IFN-gamma production in the majority of the subjects tested. IFN-gamma levels in cultures stimulated with LPG-AP were 103 +/- 81 pg/ml in individuals with asymptomatic L. chagasi infection and 127 +/- 123 pg/ml in subjects cured of visceral leishmaniasis. IFN-gamma levels in cultures stimulated with LPG-AP from subjects with asymptomatic L. chagasi infection were comparable to those observed in subjects cured of visceral leishmaniasis (P > 0.05). These data indicate that LPG-AP is recognized and induces T cell proliferation and IFN-gamma production in subjects with protective immune response against Leishmania chagasi. PMID- 8000342 TI - High frequency of specific T cell receptor rearrangements in rheumatoid arthritis: analysis of synovial fluid T lymphocytes. AB - 1. We have searched for rearrangements in the beta chain T cell receptor genes to identify clonal T lymphocyte populations in the synovial fluid of 10 patients with well established rheumatoid arthritis, using a T cell population unbiased by preselection. 2. Analysis of the restriction fragments with the beta chain constant region probe C beta 2 disclosed a rearranged band in 50% of cases (5/10). No significant differences in age, duration of the disease, treatment employed and presence of articular deformities or erosion upon X-ray examination were observed when patients with or without rearrangements were compared. 3. The rearranged band observed after BamH I digestion was of the same size in the 5 patients (14 kb). In addition, two patients presented a 10-kb rearranged band upon restriction with Hind III. 3. These data indicate that a significant number of rheumatoid arthritis patients probably present oligoclonal T cell proliferation of their synovial fluid lymphocytes. PMID- 8000343 TI - Quantitative and qualitative changes in intestinal immunoglobulin-bearing plasma cells in jejunal mucosa of 52 HIV-infected patients. AB - 1. The purpose of the present study was to evaluate the intestinal secretory immunity of HIV-infected patients. Jejunal biopsies were obtained with a Watson capsule from 52 HIV-infected patients and compared to a control group consisting of 12 healthy subjects, matched for age and sex. IgA- and IgM-containing plasma cells were studied by immunofluorescence by two independent observers who had no knowledge of the history of the slides. 2. The IgA and IgM plasma cell density was significantly decreased in HIV-infected patients when compared to the controls (31/52 for IgA and 42/52 for IgM in the HIV group and normal density in all controls). The depletion of intestinal plasma cells was an early feature of HIV disease and did not correlate with diarrhea, enteropathogens or mucosal atrophy. Although IgA plasma cell depletion has been described in HIV infection, this is the first report of IgM cell density reduction. 3. A peripheral fluorescence pattern was observed in the intestinal cells of HIV-infected patients, contrasting with the normal cytoplasmic fluorescence pattern seen in controls. The cells presenting a rim of peripheral fluorescence in HIV disease might correspond to immature B lymphocytes. 4. The intestinal plasma cell depletion may result in hampered mucosal defense in HIV disease, and is likely to be a direct consequence of T lymphocyte function impairment. 5. The data indicate that the intestinal secretory immune system is altered in AIDS and also in the early stages of HIV disease. PMID- 8000344 TI - Analysis of antibody specificity against the third variable region of the envelope glycoprotein gp120 of HIV-1 in plasma from HIV-1-positive individuals residing in Brazil. AB - 1. Antibody specificity for the principal neutralization domain (PND) of the human immunodeficiency virus type 1 (HIV-1) was studied in plasma from 122 HIV-1 infected individuals residing in Brazil. 2. Using 8 overlapping sequential pentadecapeptides corresponding to the third variable region (V3) of 5 different HIV-1 isolates in an enzyme-linked immunosorbent assay (ELISA), a preferential recognition of the peptides with amino acid sequences corresponding to the HIV-1 isolates IIIB and MN (maximal reactivities of 60-70%) compared to the isolates SC, WMJ-2 or RF (maximal reactivities below 60%) was observed. 3. A difference was observed in the overall reactivity pattern to HIV-1 SC peptides of plasma collected from individuals residing in the Brazilian states of Rio de Janeiro and Bahia. However, a statistically significant increased recognition by Bahian plasma was only observed for the HIV-1 SC C55 peptide. 4. The mean CD4/CD8 ratio of the group of plasma with an isolate-restricted recognition of peptides (0.522 +/- 0.074) was significantly lower than that of the total group of plasma (1.00 +/- 0.18). PMID- 8000345 TI - Evidence against the involvement of ACTH/CRF release or corticosteroid receptors in the anxiolytic effect of corticosterone. AB - The present study was designed to evaluate the role of ACTH and/or CRF release and corticosteroid receptors (glucocorticoid and mineralocorticoid) in the anxiolytic effect of corticosterone (CORT). Costicosteroid receptor mediation was evaluated using a dose-response analysis of the effect of CORT and by the action of dexamethasone (DEX), which binds to glucocorticoid receptors but not to mineralocorticoid receptors. DEX administration also permits indirect evaluation of the effect of ACTH/CRF release on the anxiolytic effect of CORT. Male Wistar rats (3 months old) weighing 250-350 g were treated sc with vehicle (N = 38), CORT 1.25 (N = 18), 2.5 (N = 13) and 5.0 (N = 24) mg/kg, or DEX 5.0 (N = 19) and 10.0 (N = 17) mg/kg and tested in the elevated plus-maze 2 h later. The group that received the highest dose of CORT (5.0 mg/kg) showed a significant increase in percent open arm entries (38 +/- 2.6, mean +/- SEM) as well as in percent time spent in open arms (27 +/- 4.0) when compared with the vehicle-treated rats (24.3 +/- 2.8 and 12.4 +/- 1.9, respectively; both P < 0.05). There were no other significant differences among groups in the two parameters tested or in total arm entries. These data corroborate previous findings of the anxiolytic effect of CORT and suggest that inhibition of ACTH/CRF release and corticosteroid receptors do not play a major role in the anxiolytic effect of CORT. PMID- 8000346 TI - Participation of the periaqueductal gray matter in the modulation of tonic immobility in the guinea pig. AB - Unilateral microinjection of carbachol (CCh, 1 microgram/0.2 microliter) into the specific sites in the ventral and ventrolateral portions of the periaqueductal gray (PAG) matter, which is known to be involved in analgesia, increases the duration of restraint-induced tonic immobility (TI) episodes induced in 23 adult male guinea pigs (Cavia porcellus). Mean duration of TI episodes was 107 +/- 16.38 s in the control group and increased to 220.7 +/- 40.24 s in the group microinjected with CCh. The potentiating effect of carbachol on TI duration was blocked by pretreatment with atropine (7.6 micrograms/0.4 microliter). These data suggest that PAG and the cholinergic system are involved in the modulation of the motor inhibition characteristic of TI which may be activated by the same stimuli that induce defensive analgesia. PMID- 8000347 TI - Neonatal monosodium glutamate treatment increases epididymal adipose tissue sensitivity to insulin in three-month old rats. AB - We determined the response of glucose transport to insulin in isolated adipocytes and the lipogenic activity of insulin in fragments of epididymal adipose tissue obtained from male MSG-obese rats. Basal glucose transport rates (pmol 3 min-1 10(5) cells-1) were 100% higher in MSG than in control cells (3-month old male Wistar rats) pre-incubated for 30 min (P < 0.01). Nevertheless, when expressed as fmol 3 min-1 microns 2 cell surface area-1, transport rates were similar for the two groups (31.2 +/- 2.6 for MSG and 26.5 +/- 3.2 for controls, N = 7). No differences were observed in maximally insulin-stimulated glucose transport rates between groups (72.6 +/- 10.6 for MSG and 101.0 +/- 12.0 for controls, N = 7). In contrast, for adipocytes pre-incubated for 2 h, the basal uptake rates were 3.7 times higher and the maximal response to insulin was 103% higher in cells from MSG rats compared to control cells. These alterations in MSG rat adipocytes were accompanied by changes in cell sensitivity to insulin (EC50, 0.13 +/- 0.02 ng/ml for MSG vs 0.46 +/- 0.10 ng/ml for controls, P < 0.01). The rates of incorporation of labelled substrates (3H2O and 14C-glucose) into total lipids showed that in vitro lipogenesis was also 79% (3H2O) and 250% (14C-glucose) higher in MSG adipose tissue fragments. The MSG animals were consistently hyperinsulinemic. These data suggest that the obesity of 3-month old MSG rats is a metabolic alteration characterized by an enhanced adipocyte capacity to transport glucose and to synthetize lipids resulting in increased insulin sensitivity. PMID- 8000348 TI - Blood glucose and lactate levels during hemorrhagic shock reversion by hypertonic NaCl solution. AB - 1. Several studies have shown that in irreversible hemorrhagic shock the liver is one of the first vital organs to present metabolic alterations accompanied by an increase in lacticemia. Intravenous infusion of hypertonic solutions increases mesenteric flow as well as liver perfusion, an effect which can be blocked by vagotomy. 2. In the present study we investigate the possible role of the increase in mesenteric flow in the prevention of hepatic failure evaluated by the arterial-venous difference in the generation of glucose from lactate during the reversal of hemorrhagic shock with hypertonic NaCl solution and the possible blockage of this response by bilateral vagotomy. 3. Twenty-eight male dogs, weighing 14-20 kg, were submitted to severe hemorrhagic shock. The animals were then divided into four groups: a) HYPER, 2400 mosm/l NaCl; b) SALINE, 300 mosm/l NaCl; c) HYPERVg, 2400 mosm/l NaCl immediately after bilateral vagotomy; d) SALINEVg, 300 mosm/l NaCl immediately after bilateral vagotomy. Each group received an intravenous infusion of 10% of the shed blood volume of NaCl infusion. 4. Arterial and venous samples were collected to monitor the levels of lactate, glucose and insulin. During hemorrhage, arterial and venous lactate concentrations increased. After infusion, arterial lactate levels decreased from 332 +/- 23% to 115 +/- 12% in the HYPER group in contrast to the SALINE group where it increased from 327 +/- 20% to 422 +/- 19%. 5. The decrease in arterial lactate observed after hypertonic solution infusion (2400 mosm/l), in dogs with intact vagus, suggests an increase of lactate uptake by heart and liver. Thus the beneficial effect of hypertonic solution in the reversal of hemorrhagic shock may be to enhance blood flow and oxygen delivery to the liver which would maintain glucose production and prevent hepatic failure. All the metabolic effects of hypertonic solution were abolished by vagotomy. PMID- 8000349 TI - Role of thyroid hormone in the control of growth hormone gene expression. AB - Growth hormone (GH) gene expression was examined in male Wistar rats (200 g) subjected to different manipulations of thyroid status. Thyroidectomy followed by 10 days of treatment with 0.03% methimazole added to drinking water caused a marked decrease in GH mRNA levels estimated by Northern Blot analysis. T3 administration (100 micrograms/100 g body weight, ip, twice daily) to euthyroid rats for one week caused a substantial increase in GH mRNA levels. In another set of experiments, thyroidectomized methimazole-treated rats were killed at different times after a single T3 injection (100 micrograms/100 g body weight, ip). T3 induced a prompt response in GH gene expression by 15 min that reached a maximum after 1 h, remaining so up to 4 h. We conclude that in the rat, GH gene expression is highly dependent on thyroid hormones. Because of the rapidity of the response, the effect is probably mediated by a transcriptional mechanism. PMID- 8000350 TI - Sexual development of male Wistar rats. AB - 1. Sexual development was investigated in male Wistar rats from 22 to 97 days of age by morphometric, biochemical and radioimmunological methods. 2. The first significant increase of plasma testosterone (T) occurred from 40 to 50 days of age and a progressive enhancement was observed thereafter to a maximum at 76 days (5.4 +/- 0.9 ng/ml). From that time onward, plasma T was gradually depressed to adult levels at 97 days of age (2.0 +/- 0.3 ng/ml). Plasma prolactin increased in parallel to T, reaching a maximum at 76 days (9.2 +/- 0.9 ng/ml) and attaining a lower plateau by 83 to 97 days of age (5.0 +/- 0.5 ng/ml). A small but significant increase was observed in plasma luteinizing hormone from 22 to 83 days of age. Plasma follicle stimulating hormone was high at 22 days, increased to a maximum at 40 days (15.4 +/- 0.6 ng/ml) and fell slowly to a lower plateau by 76 to 97 days of age. 3. Fructose content in the ventral prostate increased abruptly from 50 to 63 days of age (148.8 +/- 19.8 micrograms) and no significant change was observed thereafter. A progressive increase in the seminal vesicle fructose content was observed from 40 to 63 days (45.6 +/- 2.8 micrograms) when a plateau was reached. 4. The evolution of the germinal epithelium was investigated in cross-sections of seminiferous tubules analyzed at random for the presence of the most advanced germ cell and also for sperm production (estimated by the number of spermatids in stages 15 to 18 of spermiogenesis).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8000351 TI - Exercise and breast cancer: review and critical analysis of the literature. AB - Breast cancer is one of the leading causes of cancer and cancer mortality among Canadian women. Based on the current incidence rates, the National Cancer Institute of Canada has estimated that one in 10 women will develop breast cancer during her lifetime. In an effort to control this disease, various prevention strategies have been proposed. One promising strategy involves the promotion of exercise in healthy women. It has been hypothesized that exercise may protect against breast cancer by influencing regularity of ovulatory cycles, by changing body fat composition, or by enhancing natural immunity. In this paper both the epidemiological and experimental evidence that speaks to a protective effect of exercise is reviewed. Although there are several biologically plausible mechanisms for the association, the existing epidemiological and experimental data are inconclusive due to the small number of studies and their methodological insufficiencies. However, given the enormous potential benefit of even a small protective effect of exercise, further studies designed to address the relationship between exercise and breast cancer risk are warranted. PMID- 8000352 TI - Voluntary and evoked muscle contractile characteristics in active men and women. AB - Eight men and 8 women were tested for voluntary and isometric evoked contractions of the dorsiflexors. Maximal voluntary contractions were conducted isometrically (30 degrees plantarflexion) and isokinetically. Men produced greater peak torques at all but the highest isokinetic velocity. They exceeded women in measures of absolute voluntary isometric (33.8%), tetanic (46.3%), and twitch (37.9%) peak torque. Men demonstrated a higher tetanus/MVC ratio (17.8%). This ratio disparity would indicate that gender differences in peak torque in this study were more dependent upon muscle mechanisms. Although men exceeded women in measures of absolute voluntary maximum rate of torque development (MRTD) (38.7%), tetanic MRTD (39.1%), twitch MRTD (27.9%), voluntary maximum rate of torque relaxation (MRTR) (46.9%), and tetanic MRTR (41.9%), there were no significant gender differences in percentage rates of torque development or relaxation with voluntary or evoked contractions. Therefore the central and peripheral mechanisms controlling MRTD and MRTR may be similar between the sexes. PMID- 8000353 TI - The laboratory assessment of endurance performance in cyclists. AB - Performance in endurance activities depends on maximal aerobic capacity (VO2max) and the ability to sustain a high percentage of VO2max over time. This study examined whether noninvasive laboratory measures would be valid predictors of endurance performance in an individual-start bicycle race (TT). Eight experienced male cyclists (age = 25.1 +/- 3.3 years, weight = 75.0 +/- 5.7 kg, VO2max = 5.05 +/- 0.4 L.min-1) performed a progressive incremental exercise test to exhaustion on a cycle ergometer. VO2max, maximum power output, and ventilatory threshold were determined. Later the subjects completed a 40-km TT. Power output at the ventilatory threshold (VT watts) was correlated with race performance time and calculated power output during the competition (r = -0.81; r = 0.82). VT watts and VO2max accounted for 75% of the variance between subjects (r = 0.91) in performance time. These data indicate that simple laboratory measures can predict TT performance in trained cyclists. Individual differences may be accounted for by motivation, aerodynamic position, and efficiency. PMID- 8000354 TI - Effects of exercise on lactate transport into mouse skeletal muscles. AB - Skeletal muscle lactate transport was investigated in vitro in isolated fast twitch (EDL) and slow-twitch soleus (Sol) skeletal muscles from control and exercised mice. Exercise (23 m/min, 8% grade) reduced muscle glycogen by 37% in EDL (p < 0.05) and by 35% in Sol muscles (p < 0.05). Lactate transport measurements (45 sec) were performed after 60 min of exercise in intact EDL and Sol muscles in vitro, at differing pH (6.5 and 7.4) and differing lactate concentrations (4 and 30 mM). Lactate transport was observed to be greater in Sol than in EDL (p < 0.05). In the exercised muscles there was a small but significant increase in lactate transport (p < 0.05). Lactate transport was greater when exogenous lactate concentrations were greater (p < 0.05) and more rapid at the lower pH (p < 0.05). These studies demonstrated that lactate transport was increased with exercise. PMID- 8000355 TI - Neural drives to breathing during exercise. AB - This article presents the author's views about the neural drives to breathing during exercise. Two hypotheses are developed, the first being that the rapid changes in ventilation at the start and end of exercise are due to a fast neural drive whose magnitude is related to the frequency of limb movement. Experimental data are presented that this drive persists throughout exercise but declines as exercise continues. Second, the excessive increase in ventilation that occurs above the first ventilatory threshold during an incremental exercise test is due to a heavy exercise neural drive whose magnitude is related to the motor commands to the exercising muscles. Using the electromyographical activity of the working muscles as an index of the strength of the motor commands, experimental evidence is presented showing the coincidence of the first ventilatory threshold and that for the electromyographic activity of the working muscles during incremental exercise tests. PMID- 8000356 TI - Peripheral and central chemoreceptor control of ventilation during exercise in humans. AB - The stability of arterial blood gas tensions and pH during steady-state moderate exercise has suggested an important humoral element of ventilatory control in humans. However, the involvement of central and peripheral chemoreflexes in this humoral control remains controversial. This reflects, in large part, technical and interpretational limitations inherent in currently used estimators of chemoreflex "sensitivity." Evidence suggests that the central chemoreceptors (a) contribute little during moderate exercise, given the relative stability of cerebrospinal pH, (b) constrain the hyperpnea of high-intensity exercise, consequent to the respiratory compensation for the metabolic acidemia, and (c) may play a role in the respiratory compensation during chronic metabolic acidemia. In contrast, the peripheral chemoreceptors appear to (a) exert considerable influence on ventilatory kinetics in moderate exercise, but are less important in the steady state, and (b) induce much of the respiratory compensation of high-intensity exercise. PMID- 8000357 TI - Respiratory control during exercise: hormones, osmolality, strong ions, and PaCO2. AB - For optimal performance of exercising muscle, the charge state of proteins must be maintained; the pH environment of protein histidine imidazole groups must be coordinated with their pK. During exercise, increasing temperature and osmolality as well as changes in strong ions affect the pK of imidazole groups. Production of strong organic anions also decreases the concentration difference between strong cations and anions (strong ion difference, or [SID]), causing a metabolic acidosis in peripheral tissues. Central chemoreceptors regulate PCO2 in relation to the [SID] of brain fluids to maintain a "constant" brain [H+]. In addition, increased osmolality, angiotensin II, and vasopressin during exercise may stimulate circumventricular organs of the brain and interact with chemical control of ventilation. Changes in [SID] of brain fluids during exercise are negligible compared to systemic decreases in [SID]; thus, regulation of PCO2 to maintain brain [H+] homeostasis cannot simultaneously compensate for greater changes in [SID] in peripheral tissues. PMID- 8000359 TI - Models for solid-state transport: messenger RNA movement from nucleus to cytoplasm. AB - This paper explores the idea that mRNAs are transported between their transcription and processing sites in the nucleus, and their translation and degradation sites in the cytoplasm, by a 'solid-state' process. The underlying assumption is that negligible quantities of mRNA and of mRNA precursors are in solution in vivo. Therefore, mRNA transport cannot be considered as movement in the aqueous phase of the cell. The main lines of experimental evidence supporting this 'solid-state' concept are summarized and related controversies are outlined. Three possible models for a solid-state transport mechanism are discussed: a direct transfer model, with receptors organized analogously to the components of a multienzyme complex; a motor-driven model, analogous to synaptic vesicle transport in axons; and an assembly-driven model which assumes net movement along a fibril resulting from differential activities at the poles. Qualitative evaluation indicates that each of these models has characteristic advantages and disadvantages. The possibility that other nucleocytoplasmic transport processes might operate by solid-state mechanisms is briefly discussed. PMID- 8000358 TI - Do carotid chemoreceptors inhibit the hyperventilatory response to heavy exercise? AB - In this paper two types of evidence are presented which question the commonly presumed role of carotid chemoreceptor stimulation as the primary mediator of the hyperventilatory response to heavy exercise. First, carotid-body denervation in ponies increases their hyperventilatory response to heavy exercise. Second, the awake dog and the goat at rest show an immediate and substantial depression of tidal volume and of ventilation when their isolated carotid chemoreceptors are made hypocapnic. Accordingly, it is proposed that during heavy exercise the carotid chemoreceptors are inhibitory to respiratory motor output and that the cause of the hyperventilatory response originates from extrachemoreceptor, locomotor-linked, feed-forward stimuli. PMID- 8000360 TI - PCNA Ki-67 dissociation in childhood acute lymphoblastic leukaemia. An immunofluorescent laser confocal scanning microscopical study. AB - Cell proliferation rates of diagnostic marrow aspirate cells of 21 children with Acute Lymphoblastic Leukaemia and 16 controls were compared using immunocytochemical labelling of PCNA and Ki-67 antigen as assessed by Confocal Laser Scanning Microscopy. The results showed an unexpected, highly significant degree of dissociation between PCNA and Ki-67 expression in ALL blasts. The PCNA labelling indices of ALL patients were significantly increased (mean 44, range 24 77) compared with normal reactive marrow cells (mean 13.8, range 4-26) (p < 0.000001, Mann Whitney U two tailed test), suggesting an abnormal commitment to proliferation. Ki-67 expression was raised to a lesser extent in ALL cells (mean 14.8, range 1.2-35) when compared to non-malignant proliferations (mean 6.6, range 1.7-25) (p < 0.02). PCNA/Ki-67 LI ratios in ALL (mean 7, range 1.1-35) were higher than in controls (mean 2.7, range 1.04-6.5, p < 0.09). As cell proliferation rates actually achieved in the bone marrow do not differ as strongly as suggested by the extreme difference in PCNA labelling, a pathological dissociation of PCNA/Ki-67 expression exists, suggesting immortalisation. PMID- 8000361 TI - Ecto-ATPases and 5'-nucleotidases in the caveolae of smooth muscle. Enzyme histochemical evidence may indicate a role for caveolae in neurotransmission. AB - We have demonstrated the localization of ecto-Ca-ATPase and 5'-nucleotidase activity in the caveolae of smooth muscle cells of guinea pig was deferens and the ileum longitudinal muscle strips with a cerium-precipitation enzyme cytochemical method. The activities seemed to be strongest in the caveolae. Since the simultaneous presence of the 5'-nucleotidase activity supports the hypothesis that this ecto-Ca-ATPase activity does not have a pump function, but, together with 5'-nucleotidase, may play a role in neurotransmission, these specific membrane invaginations, the caveolae, have a functional relationship with transverse tubules of striated muscle. PMID- 8000362 TI - Synthesis and secretion of an estrus stage-specific protein by rat uterus. AB - A specific protein with an estimated molecular weight of 260 kDa was found to be synthesized and secreted into the incubation medium by rat uterus only during the estrus stage of the cycle. This secreted uterine protein was designated as estrus stage-specific protein (ESP). ESP was not produced by pregnant, lactating or immature pup rat uteri. Estradiol administered to ovariectomized rats induced production of ESP which was blocked by the antiestrogen, ICI 182, 780. The present results show that the synthesis and secretion of ESP is regulated by estradiol and this protein maybe involved in blastocyst implantation. PMID- 8000363 TI - Effect of extracellular K+ on hatching and outgrowth of mouse blastocysts in vitro. AB - The dependence of blastocyst development on the extracellular Na+/K+ ratio was investigated in an in vitro system. Hatching and outgrowth of mouse blastocysts was enhanced at Na+/K+ ratios between 3 and 10 compared to the ratio of about 25 typical for most culture media and serum. At a Na+/K+ ratio of 2, blastocyst hatching and outgrowth were inhibited. The requirement of blastocyst development for relatively high extracellular K+ concentrations agrees with the fact that K+ concentrations in oviduct and uterine secretions are higher than in serum. The findings can also be relevant in optimizing in vitro culturing techniques for blastocysts. PMID- 8000364 TI - Cytochalasin B-sensitive actin-mediated nuclear RNA export in germinating conidia of Neurospora crassa. PMID- 8000365 TI - Gene-specific changes of DNA methylation accompany differentiation of the slime mold Physarum polycephalum. PMID- 8000366 TI - Changes in elemental concentrations in K562 target cells after conjugation with human lymphocytes studied by X-ray microanalysis. PMID- 8000367 TI - A visual membrane immunoassay for the detection of methamphetamine using an enzyme-labeled tracer derived from methamphetamine and amphetamine. AB - A visual membrane enzyme immunoassay is described for the measurement of methamphetamine in urine. To increase assay sensitivity, tracers with chemically similar structures were cross-checked with the antibodies to determine their influence on the antibody binding. Tracers of horseradish peroxidase-labeled methamphetamine (MA-HRP) and amphetamine (A-HRP) derivatives were prepared for this purpose. Significant differences in antibody specificity were found between the two tracers. Based on the results of this study, a pair of an antibody and a tracer was selected and a membrane enzyme immunoassay (EIA) was developed utilizing the competitive binding between methamphetamine and the drug-HRP tracer. UltraBind membrane (0.45 micron) was used as the solid matrix to which the antibody was attached. Using diaminobenzidine substrate with Co2+ ion, a stable grey color appeared on the surface of membrane for MA-negative urine samples. No color appeared for MA-positive urine with a cut-off level of 0.8 ppm. PMID- 8000368 TI - A practical reagent for reversible amino-protection of insulin, 3,4,5,6 tetrahydrophthalic anhydride. AB - Of the examined dicarboxylic acid anhydrides, 3,4,5,6-tetrahydrophthalic anhydride was found to be the best reagent in practical use for reversible amino protection of insulin in terms of the rapidity of acid-deprotection. Twelve Gly(A1),Phe(B1),Lys(B29)-triacyl-insulins were prepared by reaction of porcine insulin with the dicarboxylic acid anhydrides and time courses for the deprotection of the acylated insulins with dilute acetic acid were investigated by means of capillary zone electrophoresis, and the tetrahydrophthalyl(THP) insulin obtained with the reagent was the most rapidly deacylated (6 h, 25 degrees C, 0.1 M acetic acid). Isolation of triacyl-insulins and Gly(A1)-THP-, Gly(A1),Phe(B1)-diTHP- and Gly(A1),Lys(B29)-diTHP-insulins using DEAE anion exchange high-performance liquid chromatography is also described. PMID- 8000370 TI - Studies on thermophile products. VIII. Isolation of Bacillus stearothermophilus UBT8038, a component that inhibits antigen presentation on mouse macrophages. AB - We have found a new compound from thermophile extracts which inhibits antigen presentation on mouse macrophages. The substance inhibits the expression of the class II major histocompatibility molecule (Ia). It was extracted from Bacillus stearothermophilus UBT8038 and purified by silica gel column chromatography. The isolated inhibitor, Fr. 8-A, was a phosphatidylethanolamine with isofatty acids and chemically different from any of the natural or synthetic products which have been reported to modify Ia expression. Fraction 8-A inhibits Ia expression by mouse peritoneal macrophages induced by the supernatant from concanavalin A stimulated spleen cell cultures in a dose-dependent fashion over the range 0.1-10 micrograms/ml. This fraction also exhibited inhibitory effects on antigen presentation by splenic macrophages in vitro and on the mixed leukocyte reaction. The present results show that Fr. 8-A has a unique inhibitory effect on antigen presenting cells. PMID- 8000371 TI - Enhanced cholesterol esterase activity in the pancreas of rats with streptozotocin-induced diabetes. AB - Diabetes was induced in rats by the intravenous administration of streptozotocin (STZ; 60 mg/ml). The activity of cholesterol esterase (CEase) in various tissues was determined by use of either a fluorogenic or radioactive substrate. Significant CEase activity was detected in extracts of pancreas. The specific activity of pancreatic CEase was considerably greater in pancreatic extracts from diabetic rats compared with normal rats. The activity of pancreatic CEase increased 6 d after the injection of STZ, but the difference was not statistically significant. It reached a maximum value approximately twice that of normal pancreas at 30 d with statistic significance. The highest specific activity of pancreatic CEase was found in the cytosolic fraction from diabetic rats, whereas the specific activity of the enzyme was lowest the same fraction from normal rats. PMID- 8000369 TI - Inhibitory effect of tuna peptide on endothelin production in cultured endothelial cells. AB - The effect of tuna muscle-derived angiotensin-converting enzyme (ACE) inhibitory peptide (tuna AI) on the production of potent contracting factor, endothelin-1 (ET), in the cultured bovine aorta endothelial cells (BAECs) has been investigated. ET production in the culture medium was measured by radioimmunoassay. BAECs spontaneously produced ET in a time-dependent manner for 4 to 24 h after incubation. Addition of tuna AI to the medium resulted in a time- and concentration-dependent decrease in the production of ET. The tuna AI-induced inhibition of ET production was blocked by B-3824 (bradykinin (BK) B2-receptor antagonist), NG-monomethyl-L-Arg and indomethacin, but not by angiotensin II receptor antagonist. While BK, sodium nitroprusside and platelet-derived growth factor (PDGF) significantly inhibited ET production, angiotensin II and interleukin-1 did not. Potent ACE inhibitory peptides among tuna AI analogues did not always inhibit ET production. The results suggest that tuna AI inhibits ET production at least in part via potentiation of PDGF expression in addition to potentiation of BK pathway. PMID- 8000372 TI - Reduction of neurite extension by piperine, examined on hippocampal and septal neurons in serum-free cultures. AB - The presence of piperine in a serum-free medium for 72 h markedly inhibited the neurite extension of cultured hippocampal and septal neurons under both high and low density cell culture conditions (initial cell density was 10(5) cells/cm2 and 2.5-5 x 10(3) cells/cm2, respectively). The average length of neurites decreased over a concentration range of piperine (12.5-100 microM), and the distribution of neurite population shifted towards the shorter neurite lengths whereas an increase in the soma size was observed only with high piperine concentrations (75 and 100 microM, in a high density cell culture). This indicates that the piperine effect was relatively selective to the neurite extension. The neurite extension in low density cell cultures was considerably more susceptible to piperine than that in high density cell cultures (hippocampus: EC50 = 39 versus 113 microM, septum: EC50 = 48 versus 101 microM, in the low and high density cell cultures, respectively). This difference may be due to a lack of neurotrophic supports from non-neuronal cells under the low density cell culture condition. These findings suggest that piperine, in addition to its cytotoxic effect on the neuronal survival, suppresses the neurite extension in developing neurons. PMID- 8000373 TI - The novel thromboxane A2 receptor antagonist KW-3635 abolishes the cyclic flow reduction in the canine carotid artery. AB - We tested the hypothesis that the abolition of the cyclic flow reduction (CFR) in the canine carotid artery is related to inhibition of ex vivo platelet aggregation following administration of KW-3635, a thromboxane A2 receptor antagonist, or aspirin. The CFR was induced in the carotid artery of anesthetized dogs by mechanical injury and narrowing of the artery. After induction of CFR, KW 3635 or aspirin was administered every 30 min at doses of 0,1,0.3, 1 and 3 mg/kg (i.v.). The ex vivo platelet aggregation, induced by sodium arachidonate and collagen, was also examined before and 15 min after each administration. KW-3635 and aspirin, at doses of 1 mg/kg i.v. and above, inhibited CFR and ex vivo platelet aggregation. These results that CFR in the canine carotid artery is platelet-dependent. PMID- 8000374 TI - Relation between blood pressure and plasma catecholamine concentration after administration of calcium antagonists to rats. AB - Three types of calcium antagonists, diltiazem, verapamil and nicardipine, were separately infused into Sprague-Dawley (SD) rats (under pentobarbital anesthesia n = 5) through the left femoral vein at four different flow rates. Mean arterial blood pressure, heart rate and the concentration of plasma catecholamines (CAs), epinephrine (E), norepinephrine (NE) and dopamine (DA), were measured for each calcium antagonist, and the correlations between them were studied. Blood samples were collected within the infusion from common jugular vein. Plasma concentrations of CAs were determined by a HPLC-ethylenediamine condensation reaction-peroxyoxalate chemiluminescence detection system (HPLC-ED-PO-CL). The plasma concentration of CAs increased corresponding to the blood pressure reduction. The reduction induced by each calcium antagonist correlated with the logarithm of plasma NE concentration. The relation was expressed as Y = -alpha log X+m (Y, blood pressure; X, concentration of plasma NE; alpha, slope; and m, intercept). The correlation coefficients (rs) were -0.950 (diltiazem), -0.975 (verapamil) and -0.978 (nicardipine) (versus -0.734 for control). The alpha for nicardipine (108.4) was greater than those of diltiazem (85.4) and verapamil (80.8) (versus 31.0 for control), meaning that blood pressure reduction was greater in the case of nicardipine than diltiazem and verapamil, with an identical increment of plasma NE concentration. These data indicate that the contribution of the sympathetic nervous system to maintaining blood pressure reduced by nicardipine is less than that observed following the infusion of diltiazem and verapamil. Similar good inverse correlations between blood pressure and the logarithm of plasma concentration of E were observed with the three drugs infused (r = -0.928, -0.966, and -0.948 for diltiazem, verapmil and nicardipine, respectively).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8000375 TI - Anti-osteopenic effect of nasal salmon calcitonin in type 1 osteoporotic rats: comparison with subcutaneous dosing. AB - The anti-osteopenic effect of nasal salmon calcitonin (SCT) was investigated in a type 1 osteoporotic model, Wistar rats which were ovariectomized (OVX) at age of 12 weeks, and compared with that of subcutaneous SCT. It was proved that nasal (5, 10, 20 and 40 U/rat) and subcutaneous (5, 10 and 20 U/kg) administration of SCT on alternate days for 3 weeks, starting a week after OVX, prevented the osteopenic changes of tibia and lumbar vertebra; this was proved by physicochemical parameters and histomorphometrically. A clear dose-dependent effect was seen in the trabecular bone volume of a selected regions of the 5th lumbar vertebra, and the ED50s of nasal and subcutaneous SCT calculated were 7.4 U/rat and 3.5 U/kg, respectively. The results indicate that nasal SCT is absorbed efficiently in rats with increased bone turnover to prevent rapidly developing osteopenia and that the administration route is a suitable standard method for chronically giving biodegradable anti-osteoporotic peptides to rats. PMID- 8000376 TI - Inhibition of carbon tetrachloride-induced hepatotoxicity by neopterins. AB - We investigated the inhibitory effects of neopterin (NP) and its reduced form, 5,6,7,8-tetrahydroneopterin (NPH4), on carbon tetrachloride (CCl4)-induced hepatotoxicity. In in vivo experiments, intraperitoneal administration of NP or NPH4 significantly inhibited the elevation of plasma alanine aminotransferase activity induced by CCl4 in mice. In in vitro experiments using cultured rat hepatocytes, CCl4 induced in a manner which was both time- and dose-dependent lactate dehydrogenase release, and the addition of NP or NPH4 to the culture medium significantly inhibited its release from cells. NPH4, but not NP, reacted directly with a stable radical, 1,1-diphenyl-2-picrylhydrazyl. These results suggest that NP and NPH4 inhibit CCl4-induced hepatotoxicity through different mechanisms. PMID- 8000377 TI - Effects of du-zhong leaf extract on serum and hepatic lipids in rats fed a high fat diet. AB - We evaluated the effects of Du-Zhong leaf extract on the serum and liver lipids in rats fed a high-fat diet supplemented with animal fat, cholesterol and cholate. The Du-Zhong leaf extract suppressed significantly the high-fat diet induced increases in total serum cholesterol, serum triacylglycerol and hepatic triacylglycerol but not the total hepatic cholesterol. The Du-Zhong leaf extract also suppressed the high-fat diet induced increases in very-low density lipoprotein and low density lipoprotein without affecting high density lipoprotein cholesterol. These results suggest that Du-Zhong leaf extract may be beneficial for the regulation of hyperlipidemia. PMID- 8000378 TI - Lymphocyte stimulation test with tetrazolium-based colorimetric assay for diagnosis of drug-induced allergic hepatitis. AB - The lymphocyte stimulation test (LST) is useful for diagnosing drug-induced allergy and identifying the causative drug. In this study, we examined the usefulness of 3-(4,5-dimethyl thiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) as a marker for LST in diagnosing drug allergy. In a basic study using normal peripheral blood mononuclear cells, the normal range of stimulation index (SI) was 0.92-1.38, and the mean SI for all drugs tested was 1.134 +/- 0.111 (mean +/- S.D.). The cut-off value of SI for diagnosis of drug allergy was thus set at over mean + 2S.D. for possibly positive, and at over mean + 3S.D. as a definitely positive reaction. Forty-six cases of suspected drug-induced allergic hepatitis involving 85 drugs were diagnosed by this assay, and the possibly positive and definitely positive rates were 54.3% (SI > or = 1.4) and 41.3% (SI > or = 1.5), respectively. A clinical study was made of 113 patients with diagnosed drug-induced allergic hepatitis. Forty-nine (43%) of the patients were male and 64 (57%) were female. In 85% of cases the allergic reaction occurred within one month of taking medication, but there were a number of cases in whom onset occurred after long-term incubation. The main clinical symptoms were jaundice, itching, eruption, fever, and general malaise. In about 75% of cases glutamic oxaloacetic transaminase (GOT) or glutamic pyruvic transaminase (GPT) returned to normal range within one month after medication was halted.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8000379 TI - Inhibitory activity on DNA gyrase and intracellular accumulation of quinolones: structure-activity relationship of Q-35 analogs. AB - Q-35, 1-cyclopropyl-6-fluoro-1,4-dihydro-8-methoxy-7-(3- methylaminopiperidine-1 yl)-4-oxyquinoline-3-carboxylic acid, has excellent activity against gram positive bacteria and inhibits S. aureus gyrase at concentrations more than 10 fold lower than those of other quinolones. In this paper, the effect of the C-7 and C-8 substituents of Q-35 on the inhibitory activity of gyrase purified from S. aureus, M. luteus, E. coli, and P. aeruginosa are described. In addition, intracellular accumulation of Q-35 was examined. The 50% inhibitory concentrations (IC50) of Q-35, 8-fluoro- Q-35, and 8-hydro-Q-35 on DNA gyrase purified from S. aureus were 2.5, 7.8, and 68 micrograms/ml, respectively. The IC50 on gyrase from P. aeruginosa were 11, 5.2, and 17 micrograms/ml, respectively. It is concluded that the introduction of a methoxy group into the 8 position of the quinolone leads to greater antibacterial activity against gram positive bacteria. The concentrations of Q-35 which accumulated in S. aureus and E. coli were almost equal to ciprofloxacin, but in P. aeruginosa, Q-35 was lower than ciprofloxacin. PMID- 8000380 TI - Utility of gastrointestinal physiology regulated-dogs: bioavailability study of a commercial sustained-release dosage form of theophylline. AB - The utility of gastrointestinal physiology regulated-dogs (regulated-dogs) was evaluated in a bioavailability study. The gastrointestinal physiology of beagle dogs was regulated with a combined-treatment of intramuscular pentagastrin and intravenous atropine sulfate. Theophylline has been regarded as a drug that is absorbed completely in the entire gastrointestinal tract but slowly in the colon for humans. A commercial sustained-release tablet (SR tablet) of theophylline and a commercial conventional tablet of aminophylline (theophylline hemiethilenediamine salt) were chosen as model preparations in this study. In the regulated-dogs, the drug absorption was almost complete for the conventional tablet. The bioavailability of the SR tablet accounted for 76% in the regulated dogs and 71% in intact dogs relative to that of the conventional tablet in the regulated-dogs, respectively, but no significant difference was detectable between these values. An advantage of the regulated-dogs over the intact dogs was, however, revealed in the time-profiles of the cumulative percentage of theophylline absorbed from the SR tablet, suggesting a modification of drug absorption by the prolonged arrival of the tablet to the colon. PMID- 8000381 TI - Effects of fluidity and vesicle size on antitumor activity and myelosuppressive activity of liposomes loaded with daunorubicin. AB - The effects of fluidity and vesicle size on the antitumor activity and myelosuppressive activity of liposomes loaded with daunorubicin, an anthracycline antitumor drug, were investigated in Yoshida sarcoma-bearing rats. Liposomes composed of egg phosphatidylcholine (EPC) or hydrogenated egg phosphatidylcholine (HEPC), cholesterol and dicetyl phosphate in a molar ratio of 5:4:1 were injected intravenously into rats 5 d after subcutaneous inoculation of Yoshida sarcoma. At non-effect dosage in free drug, HEPC-liposomes with a diameter of 58 or 142 nm showed the greatest inhibitory effect against Yoshida sarcoma among liposomes tested, whereas larger ones (272 nm) had weaker effect. Small EPC-liposomes (57 nm) had no effect. Larger HEPC-liposomes (especially 142 nm) greatly decreased the number of peripheral white blood cell compared with free drug at the same dose, indicating relatively strong myelosuppressive toxicity. However, small EPC- and HEPC-liposomes with a diameter of 57 and 58 nm, respectively, showed toxic effects comparable to that of free drug. Examination of the dose-dependency of therapeutic effects and toxicity indicated encapsulation of daunorubicin in the small HEPC-liposomes to enhance the therapeutic index about 3 times that of free drug. These findings indicate the possibility of using small HEPC-liposome as a drug carrier for targeting solid tumors. PMID- 8000382 TI - Uptake of liposomes surface-modified with glycyrrhizin by primary cultured rat hepatocytes. AB - Previously, we synthesized 30-stearyl glycyrrhizin (GLOSt) and reported that small unilamellar liposomes containing GLOSt (GLOSt-SUV) accumulated in the liver several times more than the control liposomes (control-SUV). In the present study, to determine the interaction between GLOSt-SUV and hepatocytes, in vitro uptake experiments were achieved with primary cultured rat hepatocytes. The uptake amount of GLOSt-SUV by rat hepatocytes was considerably higher compared to the control-SUV, while GLOSt-SUV showed about a 10-fold higher uptake level than the control-SUV during 2 h of incubation. It was assumed that GLOSt-SUV not only bind to the surface of the hepatocytes but are internalized and degraded in the cells, because at 37 degrees C, GLOSt-SUV were taken up and the level of the degradable marker was lower than the inert marker, and this did not occur at 4 degrees C. Since the uptake of GLOSt-SUV was inhibited by glycyrrhizin (GL), it was suggested that a binding-site for GL is present on the surface of hepatocytes, and GLOSt-SUV are likely to be internalized via this site by the hepatocytes. Furthermore, it was confirmed that the efficacy of GLOSt on liposomes is not affected by the fluidity of the liposomal membrane. PMID- 8000383 TI - Appearance of tolerance in the increase of contractile muscle tension by ambenonium in rats. AB - The relationship between the concentration of ambenonium (AMB), a selective and reversible acetylcholinesterase (AChE) inhibitor, in plasma and the potentiation of contractile muscle tension was investigated using a sciatic nerve-muscle preparation of rat. The developed isometric contraction was enhanced dose dependently after i.v. administration of low doses (5-20 nmol/kg) of AMB, but the contraction was weakened when AMB was administered at high doses (100-1000 nmol/kg), and the concentration-effect relationship was bell-shaped. The muscle contraction profile after 50 nmol/kg administration without previous administration, with 20 nmol/kg and with 50 nmol/kg administered previously were quite different from each other. These findings suggest that the potentiation of contractile muscle tension by AMB may be acutely tolerated and the concentration effect relationship may change time-dependently. PMID- 8000384 TI - Analysis of cytokine mRNAs induced by the administration of a highly branched (1- >3)-beta-D-glucan, OL-2. AB - OL-2, a highly branched (1-->3)-beta-D-glucan, is an antitumor glucan showing strong hematopoietic activity with weaker adjuvant activity than schizophyllan (SPG), another antitumor glucan and one which is used clinically. This paper deals with the gene expression of cytokines in mice by OL-2 and SPG in order to characterize their immunopharmacological activity. Gene expression was examined by a reverse transcriptase-polymerase chain reaction method after intraperitoneal administration of OL-2 or SPG (250 micrograms/mouse). The OL-2 administered mice strongly expressed the interleukin 1 receptor antagonist (IL-1ra) gene but SPG administered mice did not. The difference would be strongly related to the antigen-specific response between OL-2 and SPG. In the genes related to haematopoiesis, OL-2 induced G-CSF and GM-CSF, but SPG induced IL-3. These differences would relate to the pattern of haematopoietic response. Comparing the cytokine gene expression in ICR and AKR mice by OL-2 administration, the changes in cytokine gene expression were less in AKR mice administered OL-2. These findings suggest that the immunopharmacological characteristics of OL-2 are closely related, at least in part, to the activation of the complement system. The data shown in this paper also suggest that cytokine gene expression by beta glucan would be significantly affected by the structure of these glucans. PMID- 8000385 TI - Induction of osteopenia in confined rats. AB - We have developed a simple model of osteopenia in rats which is induced by confinement without requiring surgical operation. Each rat was maintained for 8 weeks in a compartment of a commercially-available wire netting cage subdivided into 10 areas (compartment size, 9 x 16 x 14 cm) to restrict exercise. The femora isolated from the confined rats showed significant decreases in mineral (calcium and phosphorus) content, compared with the level in normal rats, 2 weeks after the start of their confinement. Confined rats showed significantly lower values for the physical properties of bones such as breaking energy and breaking force and also density composed with normal rats 4 weeks after the start of confinement. KCA-098 (1 mg/kg), a new benzofuroquinoline derivative that inhibits bone resorption and at the same time stimulates bone mineralization in organ culture, protected against these decreases when given orally for 8 weeks. All these results show that confinement of rats offers a simple and useful animal model of osteopenia. PMID- 8000386 TI - Disposition of glycyrrhizin in the perfused liver of rats. AB - The disposition of glycyrrhizin (GLZ) in the perfused liver of rats after dosing in the range of 0.5-30.0 mg was investigated and a pharmacokinetic model was devised to interpret the results. The uptake rate of GLZ into the liver with respect to the unbound GLZ concentration (Cf) in the perfusate followed a Michaelis-Menten type equation with a Km,up of 1.17 micrograms/ml and Vmax,up of 13.9 micrograms/min/g of liver. The efflux clearance (0.044 ml/min/g of liver) from the liver was independent of the Cf in the liver. The biliary excretion rate at a steady-state Cf level in the liver followed a Michaelis-Menten type equation with a substrate inhibition constant (Ki,B) of 42.3 micrograms/ml, Km,B of 1.68 micrograms/ml, and Vmax,B of 3.11 micrograms/min/g of liver. The proposed model, with the holding time fitted to biliary excretion at each dose, accurately described both the perfusate concentration-time profile and the cumulative biliary excretion profile. PMID- 8000387 TI - Enhancing effect of zinc acetate on the binding of 1-nitropyrene to polydeoxyguanylic-polydeoxycytidylic acid in the hypoxanthine-xanthine oxidase system. AB - The main aim of this research was to investigate whether conformational alteration of polydeoxyguanylic-polydeoxycytidylic acid (poly[dG-dC].poly[dG-dC]) by zinc acetate would have an effect on the binding of 1-nitropyrene(1-NP) to poly[dG-dC].poly[dG-dC]. The binding of 1-NP to poly[dG-dC].poly[dG-dC] in the hypoxanthine-xanthine oxidase system in vitro was increased by zinc acetate. This increase was abolished when EDTA was added to the preincubated mixture of poly[dG dC].poly[dG-dC] and zinc ions. Neither the production of 1-aminopyrene and its expected intermediates, N-hydroxy-1-aminopyrene and 1-nitrosopyrene, nor the 1-NP remaining in the reaction mixture was altered by the addition of zinc acetate without poly[dG-dC].poly[dG-dC]. From these findings, it seems that the hypoxanthine-xanthine oxidase system is not activated by zinc acetate. On the other hand, under the same reaction conditions but the hypoxanthine-xanthine oxidase system and 1-NP, it has been reported that zinc ions or complexes transform the B-form of poly[dG-dC].poly[dG-dC] to the Z-form. Therefore, these findings indicate that the formation of the Z-form or intermediates from the B form by zinc ions may promote the binding of 1-NP to poly[dG-dC].poly[dG-dC]. PMID- 8000388 TI - Characterization of a novel heteroglucan from the rhizome of Cnidium officinale exhibiting high reticuloendothelial system-potentiating and anti-complementary activities. AB - A novel beta-heteroglucan, called cnidirhan SIIA, was isolated from the rhizome of Cnidium officinale MAKINO. It was homogeneous on electrophoresis and gel chromatography, and its molecular mass was more than 1 x 10(7). It was composed of D-glucose, D-galactose and L-arabinose in the molar ratio of 85:5:8, in addition to small numbers of O-acetyl groups. Methylation analysis and nuclear magnetic resonance studies indicated its main structural features composed of beta-1,6-linked D-glucopyranosyl residues with both 3,6- and 4,6-branching points. In addition, it has both beta-1,4-linked L-arabinopyranosyl and beta-1,6 linked D-galactopyranosyl residues. The polysaccharide showed very pronounced reticuloendothelial system-potentiating activity in a carbon clearance test, as well as a marked anti-complementary activity. PMID- 8000389 TI - A 22 kDa human growth hormone specific enzyme-linked immunosorbent assay. AB - A specific sandwich enzyme-linked immunosorbent assay (ELISA) was developed for human growth hormone (hGH) with molecular weight of 22 kDa (22k hGH). To prepare the 22k hGH specific antibody, a peptide (P-15) corresponding to residues 32-46 in 22k hGH was synthesized and used to immunize rabbits, because a 20k hGH variant was known to lack this peptide sequence. The assay method was developed using a combination of an anti P-15 polyclonal antibody (YK-2) coated on the microtiter well as a catching antibody and another polyclonal antibody against 22k hGH as a peroxidase-conjugated detecting antibody. The assay sensitivity was 1 ng/ml for 22k hGH, and cross-reactivity with other pituitary protein hormones as well as the 20k hGH variant was less than 0.01%, respectively. Furthermore, the 22k hGH content was measured precisely even in the presence of 20k hGH in this ELISA system. PMID- 8000390 TI - Mitogenic activity and the induction of tumor necrosis factor by lipopeptide analogs of the N-terminal part of lipoprotein in the outer membrane of Escherichia coli. AB - Mitogenicity and the production of tumor necrosis factor (TNF) by a chemically synthesized lipotetrapeptide analog (KAB-8), S-[2,3-bis(palmitoyloxy)-2R-propyl] N-[(2,2,2)-trichloro- ethoxycarbonyl: Troc group]-(R)-cysteinyl-(S)-seryl-(S) seryl-(S)-asparagine, the amino acid sequence of which corresponds to that of the lipopeptide part of lipoprotein in Escherichia coli, and several derivatives (KAB 30-41), which possessed the altered glycerocysteine moiety, were examined. A 1 cysteinyl glycerol skeleton-type compound (KAB-8), a propane-type compound (KAB 31), a homoglycerol-type (KAB-39 and 40) and a 2-cysteinyl glycerol-type (KAB-41) exhibited mitogenic activity on splenocytes from C3H/He mice at various concentrations ranging from 0.4 to 100 micrograms/ml. However, propane-type compounds, except KAB-31, and ethane-type compounds showed lower mitogenic activity than other types of compounds. Compounds KAB-8, 31, 40 and 41 induced the production of TNF in peritoneal exudated macrophages from C3H/He mice at concentrations of 25 and 50 micrograms/ml. The results indicate that the structural differences of the glycerol moiety in the synthetic lipopeptides affect the potency of its biological activities. PMID- 8000391 TI - Preparation of monoclonal antibodies for immunoblotting human growth hormone receptor and growth hormone-binding protein. AB - Monoclonal anti-peptide antibodies against the extracellular domain of human growth hormone receptor (hGHR) were prepared. Four monoclonal antibodies (mAbs) reacted with an extracellular domain protein produced by genetic engineering. Among them, GHRP2-88 was the most reactive against hGHRs from human IM-9 cells. The lower limit of detection for immunoblotting using this mAb was about 200 pg hGHR. The GHRP2-88 antibody also reacted with deglycosylated hGHRs from tunicamycin-treated IM-9 cells and with the growth hormone-binding protein (GH BP) in human plasma. PMID- 8000392 TI - Effect of vinconate on long-term potentiation in a mossy fiber-CA3 system of guinea pig hippocampal slices. AB - We investigated the effect of vinconate on the long-term potentiation of population spikes following the stimulation of mossy fibers in the CA3 pyramidal layer of hippocampal slices from guinea pig brain. Vinconate (10(-7) and 10(-6) M) dose-dependently augmented the long-term potentiation in the mossy fiber-CA3 system. This effect was reduced by treatment with scopolamine at a concentration of 10(-6) M, which showed no significant change in the long-term potentiation in a mossy fiber-CA3 system. These results suggest that vinconate may augment long term potentiation in the mossy fiber-CA3 system partly via activation of the cholinergic system. PMID- 8000393 TI - Ursolic acid inhibits aflatoxin B1-induced mutagenicity in a Salmonella assay system. AB - An attempt was made to isolate the active component of Eriobotrya japonica, which inhibits aflatoxin B1-induced mutagenicity in the Salmonella assay system. The number of revertants per plate was significantly decreased when a MeOH extract of Eriobotrya japonica was added to the assay system using Salmonella typhimurium TA100 or TA98. Furthermore, we examined the effect of each fraction purified from the MeOH extract, and an EtOAc fraction was found to be the most effective. Ursolic acid isolated from the EtOAc fraction markedly and significantly decreased the numbers of Salmonella typhimurium TA100 revertants per plate, thus showing antimutagenic activity. PMID- 8000394 TI - Novel selective inhibitor of alpha-amylase isoenzymes. PMID- 8000395 TI - [About a good use of consensus conferences]. PMID- 8000396 TI - [Value of vertebroplasty combined with surgical decompression in the treatment of aggressive spinal angioma. Apropos of 3 cases]. AB - Vertebral hemangiomas can cause difficult-to-treat neurological complications. We report our experience with three such cases. Patients no. 1 and 2 were females aged 64 and 71 years, respectively; patient no. 1 had a two-year history of weakness in the lower limbs and patient no. 2 had a five-month history of back pain. Both these patients had a pyramidal syndrome in the lower limbs. Patient no. 3 was a 61 year old male with a one-year history of left sciatica. Roentgenograms were suggestive of a hemangioma occupying the entire T8 (cases 1 and 2) or L5 (case 3) vertebra. Computed tomography and magnetic resonance imaging confirmed this diagnosis and showed that patients 1 and 2 had an anterior epidural hemangioma opposite T8 impinging on the spinal cord. In patients 1 and 2, treatment consisted in embolization of T8 followed by transpedicular injection of 6 cc of methylmethacrylate into the body of T8. One cubic centimeter of histoacryl was also injected in each lamina. The third patient had a similar vertebroplasty procedure without prior embolization since he had no epidural hemangioma. One patient (no. 1) developed intercostal neuralgia of several hours duration after the procedure. All three patients subsequently underwent laminectomy (T7-T8 with removal of the epidural hemangioma in cases 1 and 2, L5 in case 3). The pyramidal syndrome resolved within 15 days in patients 1 and 2; the nerve root pain resolved within 48 hours in patient 3.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8000397 TI - [Leukocyte expression of the LFA-1 adhesion molecule in spondylarthropathies]. AB - The expression of adhesion molecule Leukocyte Function Antigen-1 (LFA-1) on peripheral blood leukocytes was evaluated (using a monoclonal antibody anti CD11a/LFA-1) in 52 spondylarthropathies (SA) (35 HLA B27 positive), 12 healthy patients, 24 active rheumatoid arthritis (RA) and 12 systemic lupus (SLE) patients. LFA-1 expression on lymphocytes was similar in the different groups of patients, but LFA-1 expression on granulocytes was higher in SA than in controls (p < 0.05) or in RA or SLE. Fluorescence intensity of anti LFA-1 staining on SA granulocytes correlated with serum IgA levels. There was no difference between HLA B27 positive/negative, biologically inflammatory (CRP > 21 mg/l)/non inflammatory SA patients. This study seems to confirm the granulocyte and IgA involvement in immunopathogenesis of spondylarthropathies. PMID- 8000398 TI - [Etiologies of chronic polyarthritis in Lome (Togo)]. AB - Medical records were reviewed retrospectively to determine the causes of chronic polyarthritis in patients attending a hospital outpatient clinic in Lome (Togo). Among 2812 patients seen over 44 months, 70 (2.5%; 28 female, 42 male) had polyarthritis of at least three months' duration. Twenty-six patients (17 female, 9 male), with a mean age of 30 years at disease onset, had isolated, nondestructive polyarthritis mainly involving the distal appendicular joints and responsible for short-lived flares usually adequately controlled by nonsteroidal antiinflammatory agents alone; antinuclear antibodies were looked for in 16 of these patients with positive results in eight. The favorable outcome and negative tests for rheumatoid factors differentiated this condition from rheumatoid arthritis. None of the 26 patients had systemic manifestations possibly suggestive of connective tissue disease. Diagnoses in the 44 remaining patients included gout (n = 15), spondyloarthropathy (n = 12), rheumatoid arthritis (n = 12), juvenile chronic arthritis (n = 2) and human immunodeficiency virus infection (n = 3). These data confirm that rheumatoid arthritis is infrequent in West Africa. The leading cause of chronic polyarthritis in Lome may be mild isolated nondestructive polyarthritis reminiscent of adult-onset oligoarthritis with antinuclear antibodies. Long-term follow-up and immunological evaluation of patients with this condition can be expected to provide valuable pathogenic and nosologic information. PMID- 8000399 TI - [The future of carpal tunnel syndrome]. PMID- 8000400 TI - [Bone architecture and mechanical resistance]. PMID- 8000401 TI - [Ankylosing gout. Apropos of 2 cases]. AB - Development of ankylosis of joints involved with gouty arthritis is an exceedingly rare event of which only ten examples have been reported. Most patients had chronic, tophaceous gout that had not received adequate medical attention. The authors report two new cases including one in a patient with no documented history of acute gout. The first patient was a 72 year old noninsulin dependent diabetic male who had been given a diagnosis of gouty polyarthritis with tophi seven years earlier. The second was a 42 year old male with no history of acute gout in whom hyperuricemia had been diagnosed at the age of 22 years upon evaluation for obesity. Both patients had ankylosis of the ankles and proximal interphalangeal joints of the hands. A marked decrease in range of motion of the wrists was found in the second patient. Roentgenograms showed complete ankylosis of the tarsus and partial ankylosis of the tibiotarsal joints in both patients, as well as ankylosis of the carpus in the second patient. The pathophysiology of ankylosis during gouty arthritis is poorly understood. A pannus containing abundant urate crystals is found upon pathological examination. Antihyperuricemic agents can reverse urate deposition but have no effect on ankylosis. PMID- 8000402 TI - [Synovitis caused by plant thorn and chronic polyarthritis. Apropos of a case and review of the literature]. AB - A 54 year old male developed plant thorn synovitis of the knee followed five months later by nonerosive seronegative polyarthritis. The occurrence of chronic inflammatory joint disease shortly after plant thorn synovitis is exceedingly rare. The relationship between the two events remains to be clarified. PMID- 8000403 TI - [Scaphoid fissure in algodystrophy: diagnostic value of MRI]. AB - Stress fractures are exceptional in patients with reflex sympathetic dystrophy syndrome, even when bone loss is severe. We report a case of stress fracture of the navicular bone documented by magnetic resonance imaging. Recurrence of localized pain in patients with reflex sympathetic dystrophy syndrome suggests either a relapse of the syndrome or a bony fissure. Magnetic resonance imaging can provide early differentiation of these two conditions. PMID- 8000404 TI - [Myasthenia caused by D-penicillamine in rheumatoid arthritis]. PMID- 8000405 TI - [Bone scintigraphy disclosing pulmonary hyperfixation in hypercalcemia]. PMID- 8000406 TI - [Immuno-scintigraphy in the diagnosis of distal bone metastasis of colonic cancer]. PMID- 8000407 TI - [Dermatomyositis associated with monoclonal gammopathy]. PMID- 8000408 TI - [Scanner and mechanical lumbar diseases in private practice. Apropos of 106 patients covered by the Caisse Maladie Regionale du Nord]. AB - The aim of this study was to prospectively evaluate use of computed tomography (CT) of the lumbar spine in office practice. The "Caisse Maladie Regionale du Nord" provides health insurance to self-employed retailers and craft persons (92,500 people at the end of 1991). The authors prospectively studied 106 patients insured by this organisation (60 males, 46 females, mean age: 51.27 years) who underwent CT of the lumbar spine between August 2, 1991 and January 23, 1993. They examined all insurance claims (physician visits, surgery, drugs, physiotherapy, laboratory tests, imaging studies, and hospitalizations) filed by each study patient during the 4 months before and the 4 months after the index CT. Reason for the CT, specified on 65 of the 106 radiologist reports, were isolated low back pain and nerve root pain in 26.2% and 56.9% of the patients respectively. CT findings were discal prolapse in 27 patients (25.5%), facet joint osteoarthritis in 33 patients (31.3%), discal protrusion in 29 patients (27.4%) and were considered as normal in 19 patients (18%). CT was preceded by plain radiographs in 50% of patients, by a rheumatologist visit in 31%, by a visit to the sole general practitioner in 51%, by local steroid injection in 15%. During the 4 months subsequent to the index CT, 14 (13.2%) patients had surgery and one underwent chemonucleolysis. These findings suggest that consensus conference recommendations concerning lumbar spine CT are not currently being followed in France. PMID- 8000409 TI - TB treatment: yesterday, today and ... tomorrow. PMID- 8000410 TI - Educational aspects of tuberculosis control in Europe. PMID- 8000411 TI - The International Respiratory Care Club (IRCC) PMID- 8000412 TI - Inhaled platelet-activating factor increases airway sensitivity but not maximal airway narrowing to methacholine in normal subjects. AB - To examine the effect of inhaled platelet-activating factor (PAF) on airway sensitivity and on maximal airway narrowing, we measured airway response to doubling concentrations of methacholine (MCh) 48 h before and 48 h after inhalation of 10, 50 and 100 micrograms of PAF in six nonatopic, nonasthmatic subjects. The forced expiratory volume in one second (FEV1) and airflow at 30 percent of vital capacity (V30) from partial forced expiration were used to assess changes in airway calibre. Inhalation of PAF caused only minor changes in FEV1. In contrast, inhalation of 100 micrograms of PAF caused a significant fall in V30 from 2.64 +/- 0.35 to 1.35 +/- 0.43 l.min-1 (p < 0.05). Two days after PAF inhalation a leftward shift of the concentration-response curve to MCh was observed. The MCh concentration causing a 20% fall in FEV1 (PC20FEV1) was 11.25 +/- 1.78 and 2.38 +/- 1.29 mg.ml-1 (geometric mean +/- GSEM; p < 0.05) before and after PAF inhalation, respectively. PAF did not affect the maximal airway response to MCh. The maximum percentage fall in FEV1 was 36.2 +/- 1.9% at baseline and 37.6 +/- 1.8% after PAF inhalation. Likewise, maximum percentage change in V30 was 72.8 +/- 3.7% at baseline and 73.6 +/- 3.4% after PAF inhalation. The results of this study show that PAF inhalation increases airway sensitivity without altering the maximal bronchoconstrictive response to MCh in normal subjects. PMID- 8000413 TI - Ventilatory lung function level as a predictor of survival among the elderly. AB - During a population survey in 1986/1987 among community-dwelling elderly in Cracow, aged 65 yrs and over, measurements of ventilatory lung function were carried out on 698 males and 1,211 females. The main objective of the study was to assess the importance of forced expiratory volume in one second (FEV1) as a predictor of survival experienced in this population group over a 6 year follow up, in comparison with that of sociodemographic variables, smoking habit, chronic respiratory symptoms, hypertension, obesity and self-assessment of health. Statistical analysis of the relationship between mortality and chosen predictors has been performed with Cox proportional hazards statistical model. It was found that in addition to age, the FEV1 level was the most relevant and independent of age survival predictor among the elderly. In males, a reduction of FEV1 by 100 ml after allowing for age, showed a significantly higher risk of dying by 4%, (relative risk (RR) = 1.04; 95% confidence interval (CI) 1.01-1.06), and in females by 5% (RR = 1.05; 95% CI 1.05-1.09). Male current or ex-smokers displayed a higher mortality risk due to reduction of FEV1 (RR = 1.05; 95% CI 1.01-1.09) compared to lifetime nonsmokers (RR = 1.04; 95% CI 1.00-1.07); the corresponding RR values in women were 1.12 (95% CI 1.02-1.23) and 1.04 (95% CI 1.00-1.08), respectively. However, the differences found between the smokers and nonsmokers were not significant in either gender group. Other potential predictors considered, such as education, chronic respiratory symptoms, hypertension, self assessment of health, or obesity, appeared to have been irrelevant in the multivariate analysis. PMID- 8000414 TI - Thoracotomy in patients over 70 years old. AB - One hundred cases of patients aged 70 yrs or older, who had undergone surgical intervention for a thoracic pathology between 1981 and 1990, were reviewed. The mean age was 73 yrs, and bronchial cancer the most frequent aetiology (55%). A systematic detailed study before surgery is recommended in the these patients, who have the highest operative risk, and whom we should try to treat most conservatively. Although the rate of complications was higher than the normal average, mortality was only 4%, and was related to the greater or lesser aggression of the surgery. In cases of diagnosed bronchial cancer, a survival of 2 yrs was obtained in 66%, 3 yrs in 50%, and 5 yrs in 26%. We conclude that, theoretically, at the age of 70 yrs or older there is no contraindication for surgery, although it does increase the postoperative morbidity. PMID- 8000415 TI - Preventive treatment of chronic bronchitis: a meta-analysis of clinical trials with a bacterial extract (OM-85 BV) and a cost-effectiveness analysis. AB - Chronic bronchitis is a lifelong disease with significant effects on the patient and on the costs to health insurance institutions. Acute exacerbations in chronic bronchitic patients may have a negative impact on patients' quality of life and on the progression of the disease, particularly in more severe patients. The clinical efficacy of the immunoactive bacterial extract OM-85 BV has been shown in several clinical trials, a cost-effectiveness evaluation (CEA) of its use in chronic bronchitic patients has not been fulfilled so far. In this study a meta analysis on the preventive treatment of acute exacerbations with OM-85 BV and a CEA, focusing on direct costs only, was performed. The meta-analysis showed a mean value of 0.6 prevented acute exacerbations per 6 months per patient, and a reduction of 9 days in antibiotic treatment per 6 months per patient. CEA evaluated the different cost elements. The mean direct cost (consultations, antibiotics, etc.) for the treatment of 1 acute exacerbation in chronic bronchitic patients was calculated as 143, 459 Lira. Thus for 0.6 prevented acute exacerbations per 6 months per patient a reduction in cost of 86,075 Lira (0.6 143,459) could be expected. The additional costs for the preventive treatment with OM-85 BV, based on prices for Italy, are 34,980 Lira per patient per 6 months. In conclusion, the effective cost savings per patient per 6 months are 51, 095 Lira. The sensitivity analysis revealed only one critical parameter, i.e. the clinical effectiveness of OM-85 BV. Even assuming 0.3 prevented exacerbations per 6 months per patient, the preventive treatment still proved to be cost effective. PMID- 8000416 TI - Pulmonary oedema and hypotension induced by hydrochlorothiazide. AB - We present the case of a patient with acute onset of dyspnoea after a long distance flight. Pulmonary embolism was suspected, but could be excluded by perfusion scintigraphy. The electrocardiogram and chest X-ray were compatible with acute myocardial infarction and pulmonary oedema, but the slightness of the elevation of pulmonary capillary wedge pressure allowed cardiogenic pulmonary oedema to be excluded. The clinical picture was then interpreted as pneumonia with sepsis and hypotension. The rapid and full clinical recovery within 48 h, together with the close temporal relationship of ingestion of hydrochlorothiazide and the onset of symptoms, allowed the diagnosis of drug-induced pulmonary oedema and anaphylactoid hypotension. PMID- 8000417 TI - Noninvasive mechanical ventilation in the treatment of acute respiratory failure due to infectious complications of lung transplantation. AB - Patients that have undergone lung and heart-lung transplantation may contract severe respiratory infections, often leading to acute respiratory failure requiring mechanical ventilation. Endotracheal intubation may induce infectious complications of the respiratory tract, which can be avoided by noninvasive modes of ventilation. We describe the use of noninvasive modes of ventilation in three cases of acute respiratory failure induced by infectious complication of lung and heart-lung transplantation. In two cases endotracheal intubation was avoided and treatment was successful. PMID- 8000418 TI - Atelectasis formation and gas exchange impairment during anaesthesia. AB - Anaesthesia is accompanied by impaired oxygenation of the blood, and sometimes hypoxaemia may develop despite an increased oxygen fraction of the inspired gas. The major cause of this derangement is shunt, an effect of prompt atelectasis formation in dependent lung regions. An additional cause is ventilation/perfusion (V/Q) mismatch, possibly produced by intermittent airway closure. The magnitude of shunt and size of atelectasis are independent of the age of the patient, whereas V/Q mismatch increases with age, explaining the age dependent impairment of oxygenation. PMID- 8000419 TI - Role of ANCA in the pathogenesis of Wegener's granulomatosis: a short review. AB - The presence of autoantibodies to neutrophil cytoplasmic proteinase-3, usually reported as c-ANCA, is virtually diagnostic for Wegener's granulomatosis and related conditions. These antibodies are highly associated with active systemic disease, and may be implicated in pathogenesis. In vitro, c-ANCA can induce a respiratory burst and degranulation of cytokine-primed neutrophils, leading to lysis of cultured endothelial cells. This and other putative pathogenic mechanisms are reviewed. PMID- 8000420 TI - Treatment of tuberculosis and tuberculosis infection in adults and children. American Thoracic Society. AB - 1. A 6-mo regimen consisting of isoniazid, rifampin, and pyrazinamide given for 2 mo followed by isoniazid and rifampin for 4 mo is the preferred treatment for patients with fully susceptible organisms who adhere to treatment. Ethambutol (or streptomycin in children too young to be monitored for visual acuity) should be included in the initial regimen until the results of drug susceptibility studies are available, unless there is little possibility of drug resistance (i.e., there is less than 4% primary resistance to isoniazid in the community, and the patient has had no previous treatment with antituberculosis medications, is not from a country with a high prevalence of drug resistance, and has no known exposure to a drug-resistant case). This four-drug, 6-mo regimen is effective even when the infecting organism is resistant to INH. This recommendation applies to both HIV infected and uninfected persons. However, in the presence of HIV infection it is critically important to assess the clinical and bacteriologic response. If there is evidence of a slow or suboptimal response, therapy should be prolonged as judged on a case by case basis. 2. Alternatively, a 9-mo regimen of isoniazid and rifampin is acceptable for persons who cannot or should not take pyrazinamide. Ethambutol (or streptomycin in children too young to be monitored for visual acuity) should also be included until the results of drug susceptibility studies are available, unless there is little possibility of drug resistance (see Section 1 above). If INH resistance is demonstrated, rifampin and ethambutol should be continued for a minimum of 12 mo. 3. Consideration should be given to treating all patients with directly observed therapy (DOT). 4. Multiple-drug-resistant tuberculosis (i.e., resistance to at least isoniazid and rifampin) presents difficult treatment problems. Treatment must be individualized and based on susceptibility studies. In such cases, consultation with an expert in tuberculosis is recommended. 5. Children should be managed in essentially the same ways as adults using appropriately adjusted doses of the drugs. This document addresses specific important differences between the management of adults and children. 6. Extrapulmonary tuberculosis should be managed according to the principles and with the drug regimens outlined for pulmonary tuberculosis, except for children who have miliary tuberculosis, bone/joint tuberculosis, or tuberculous meningitis who should receive a minimum of 12 mo of therapy.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8000422 TI - Leukotriene inhibition in asthma therapy. PMID- 8000421 TI - Accuracy of nine commercially available pulse oximeters in monitoring patients with chronic respiratory insufficiency. AB - 9 pulse oximeters (BIOX-III, Nellcor 250, Jaeger CNS, Micro2), Pulsox-8, Oxycount, PulsOXImeter, PalcoLabs and Pulsox-7) were studied in 90 COPD patients. The transcutaneus oxygen saturation (SaO2%) was compared with arterial oxygen saturation calculated simultaneously with drawn blood samples (AVL-995). The measurement of error distribution and the cumulative distribution function (CDF) of measurement errors allows ranking of the pulse oximeters, which can be divided in 3 groups. We conclude that the accuracy of the tested nine pulse oximeter does not enable precise absolute measurements, specially at lower oxygen saturation ranges. PMID- 8000423 TI - Measurement of exhaled nitric oxide and chest disease. PMID- 8000424 TI - Expression of alpha-amylases, carbohydrate metabolism, and autophagy in cultured rice cells is coordinately regulated by sugar nutrient. AB - A rice suspension cell culture system has been established to study how sugar depletion regulates alpha-amylase expression, carbohydrate metabolism, and other physiological and cellular changes. It is shown here that a group of 44 kDa alpha amylases are constitutively expressed whether or not the cells are starved of sucrose. However, expression of a new group of alpha-amylases of 46 kDa is dramatically induced when cells are starved of sucrose. Cellular sugar and starch were rapidly consumed and metabolic activity was decreased in the starved cells. Extensive autophagy also occurred in the starved cells, which caused an increase in vacuolar volume and degradation of cytoplasmic constituents including amyloplasts. Immunocytochemical studies revealed that alpha-amylases are localized in starch granules within amyloplasts, in cell walls, and in some of the vacuoles. The presence of putative signal sequences in the N-termini of nine rice alpha-amylases suggests hitherto unidentified pathways for import of alpha amylases into amyloplasts. The studies show that differential alpha-amylase expression, carbohydrate metabolism, metabolic activity, and vacuolar autophagy are coordinately regulated by the sugar level in the medium. As the starved suspension cells exhibit some sugar-regulated characteristics of alpha-amylase expression in germinating rice embryos as well as physiological changes similar to those in senescing cells, this system represents an ideal tool for studying cellular, biochemical, and molecular biological aspects of alpha-amylase gene regulation, carbohydrate metabolism, senescence, and protein targeting in plants. PMID- 8000425 TI - The Arabidopsis ribonuclease gene RNS1 is tightly controlled in response to phosphate limitation. AB - Two stimuli that have been associated with nutrient remobilization in plants are phosphate (P(i)) starvation and senescence. Little is known about how the nutrient remobilization machinery is induced at the molecular level, but in the case of P(i) starvation, ribonucleases are considered to play important roles in the remobilization process. Here, the control of two closely related ribonuclease genes of Arabidopsis, RNS1 and RNS3 is investigated. The RNS1 gene is sharply induced during starvation for P(i), an effect specific among the major macronutrients, whereas RNS3 transcript levels remain relatively constant. RNS1 and RNS3 produced in yeast co-migrate with Arabidopsis ribonuclease activities that exhibit the same induction properties as the transcripts in both wild-type plants and the pho1 mutant, which is defective in xylem loading of P(i). In contrast to what occurs during P(i) starvation, both RNS1 and RNS3 are modestly induced during senescence, indicating that the two stimuli could trigger different signal transduction pathways. The characterization of RNS1, in particular, provides an important first step towards elucidating the mechanisms by which plants sense and respond to P(i) limitation, a prominent condition in many soil types. PMID- 8000426 TI - A phloem-specific sucrose-H+ symporter from Plantago major L. supports the model of apoplastic phloem loading. AB - In this paper the cloning of a full-length cDNA clone encoding the PmSUC2 sucrose H+ symporter from Plantago major is described. This plant allows the simple preparation of vascular bundles from the basal regions of fully developed source leaves and thus a separation of vascular and non-vascular tissue. A cDNA library was constructed from poly(A)+ RNA isolated from vascular bundles and used for the subsequent cloning of cDNAs. The respective mRNA is specifically expressed in the vascular bundles as shown on Northern blots of total RNA from vascular and non vascular tissues. The PmSUC2 protein has 12 putative transmembrane helices and is highly homologous to other plant sucrose transporters. Substrate specificity and energy dependence of the transporter encoded by this cDNA were determined by expression in baker's yeast Saccharomyces cerevisiae. The PmSUC2 protein catalyses the transport of sucrose into transgenic yeast cells. Invertase null mutants of yeast expressing PmSUC2 accumulate sucrose more than 200-fold. This transport was sensitive to uncouplers or SH-group inhibitors. Plasma membranes from yeast cells expressing the PmSUC2 protein were purified and fused to proteoliposomes containing cytochrome-c-oxidase. In this system sucrose is accumulated only when proton motive force is generated, indicating that PmSUC2 is a sucrose-H+ symporter. The apparent molecular weight of the PmSUC2 protein is 35 kDa on 10% SDS-polyacrylamide gels. The presented data strongly support the theory of phloem loading from the apoplastic space by a sucrose-H+ symporter. PMID- 8000427 TI - A NaCl-regulated plant gene encoding a brain protein homology that activates ADP ribosyltransferase and inhibits protein kinase C. AB - A cDNA clone pCZ1, with a 1.1 kb insert, was isolated from a NaCl-adapted tobacco cell cDNA library that encodes an apparently full-length 29 kDa protein (251 amino acids) with a calculated pI of 5.7. The encoded peptide had a high amino acid sequence identity with bovine 14-3-3 protein which was originally found as an abundant protein in the animal central nervous system. Recently, proteins with sequence identity to 14-3-3 protein have also been found in plants, insects and yeast, and appear to have diverse physiological functions. Similar to the bovine brain 14-3-3 protein, the recombinant pCZ1 protein stimulated ADP-ribosylation of protein substrate by ADP-ribosyltransferase from the plant and animal pathogenic bacterium Pseudomonas aeruginosa. This recombinant protein also inhibited protein kinase C activity in vitro. Southern blot analyses indicated that most likely five genes encoding 14-3-3-like proteins are present in tobacco. The pCZ1 cDNA insert hybridized to a single mRNA of 1.1 kb from cultured tobacco cells. The level of this mRNA transcript in tobacco cells was downregulated upon adaptation to NaCl but was unaffected by short-term treatment with NaCl, ABA or ethylene. In tobacco plants, expression of transcript that hybridized to pCZ1 was tissue specific, and was most abundant in roots and flower parts. Monoclonal antibody raised against GF14 protein, a maize protein with substantial sequence identity with 14-3-3 protein detected two bands on SDS-PAGE of total proteins from unadapted tobacco cells and only a single band from cells adapted to NaCl. The GF14 antibody was also used to illustrate that the G-box element of a salt induced gene is associated with a 14-3-3-type protein. PMID- 8000428 TI - Production of the Escherichia coli betaine-aldehyde dehydrogenase, an enzyme required for the synthesis of the osmoprotectant glycine betaine, in transgenic plants. AB - In several organisms osmotic stress tolerance is mediated by the accumulation of the osmoprotective compound glycine betaine. With the ambition to transfer the betaine biosynthetic pathway into plants not capable of synthesizing this osmoprotectant, the Escherichia coli gene betB encoding the second enzyme in the pathway, betaine-aldehyde dehydrogenase was introduced into Nicotiana tabacum. The betB structural gene was fused to the promoter of ats1a, a gene coding for the small subunit of Rubisco in Arabidopsis thaliana. Two types of constructs were made, either encoding the N-terminal transit peptide for chloroplast targeting or without the targeting signal for cytoplasmic localization of the BetB polypeptide. Analysis of transgenic N. tabacum plants harboring these constructs showed that in both cases the transgenes were expressed. Northern analysis of the plants demonstrated the accumulation of betB-related mRNA of the correct size. The production and processing of the corresponding polypeptides could be demonstrated by immunoblotting using polyclonal antisera raised against the BetB polypeptide. The transit peptide encoded by ats1a was able to direct BetB to the chloroplast, as suggested by the presence of the correctly processed BetB polypeptide in the chloroplast fraction. High betaine-aldehyde dehydrogenase activity was detected in transgenic plants, both in those where the chimeric gene product was targeted to the chloroplast and those where it remained in the cytoplasm. The transgenic tobacco acquired resistance to the toxic intermediate, betaine aldehyde, in the betaine biosynthetic pathway indicating that the bacterial enzyme is biologically active in its new host. Furthermore, these transgenic plants were able to convert exogenously supplied betaine aldehyde efficiently to glycine betaine. PMID- 8000429 TI - A self-stabilizing Ac derivative and its potential for transposon tagging. AB - With the goal of developing a self-stabilizing transposon tagging system, a derivative of the maize transposable element Ac (Ds303) harbouring a deletion between bp 246 and 736 has been introduced into tomato (Lycopersicon esculentum) by Agrobacterium tumefaciens-mediated transformation. The deletion removes the major transcription start site, 84 bp of the putative Ac promoter and part of the untranslated leader. Transpositions from the T-DNA, where Ds303 was inserted between the mannopine synthase 1' promoter and the GUS gene, were observed in four independent transgenic plants analysed. After transposition the transposed Ds303 elements were stably integrated in the genome and could not transactivate a tester Ds element. However, somatic and germinal transpositions of the transposed Ds303 elements occurred in the presence of a transposase source. PMID- 8000430 TI - Regulation of human protein C gene expression by the mouse WAP promoter. AB - A 4.1 kb mouse whey acidic protein (mWAP) promoter was cloned from a C57BL/6 cosmid library. The tissue-specific and developmental pattern of expression of a hybrid gene comprised of the mWAP promoter fragment and the human protein C (HPC) gene was analysed in transgenic mice. The corresponding RNA was detected mainly in the mammary gland, with 'leakage' of expression in the salivary gland and kidney. The developmental pattern of transgene expression differed from that of the endogenous WAP gene. In particular, recombinant HPC (rHPC) transcripts were detected earlier in pregnancy than WAP RNA, with no significant increase during lactation. This indicates that regulatory elements responsible for developmental regulation are located outside the 4.1 kb mWAP gene promoter fragment, or if present, may be subject to position effects. Precocious expression of the transgene did not compromise the health or nursing abilities of transgenic females. Expression of rHPC affected the appearance of the mammary alveoli and alveolar epithelial cells in lactating transgenic mice. The alveoli were less distended and alveolar epithelial cells appeared cuboidal with centrally positioned nuclei. We suggest that the inefficient intracellular processing of rHPC can alter the histological appearance of alveolar epithelial cells in the transgenic mammary gland. PMID- 8000431 TI - Expression of the pea albumin 1 gene in transgenic white clover and tobacco. AB - In order to improve the quality of pasture protein for ruminant animal nutrition, we are introducing genes encoding rumen-protected proteins, rich in essential amino acids, into white clover (Trifolium repens L.). We have introduced a chimaeric gene transcribed from the 35S CaMV promoter, and encoding the pea albumin 1 (PA1) protein, rich in sulphur amino acids, into the white clover genotype WR8 by Agrobacterium-mediated transformation. A transgenic plant with high levels of PA1 mRNA was crossed with a commercial genotype from cv. Regal Ladino and both the parent and progeny plants were analyzed for expression and accumulation of PA1 gene products. Steady-state mRNA levels and transcript sizes in transgenic parent and progeny were comparable. The abundance and stability of the PA1 protein in transgenic white clover plants was examined by immunoselection of in vivo [35S]Na2SO4-labelled plant proteins. Evidence is presented here, that the 11 kDa PA1 proprotein precursor is processed correctly in petiole tissues of newly regenerated white clover plantlets but only the 6 kDa PA1a subunit accumulates in leaflets of tissue-culture-grown and older glasshouse-grown clover plants. Attempts to enhance PA1 abundance by altering its subcellular target in transgenic tobacco plants suggest that the endomembrane system is a relatively stable environment compared with the cytoplasm or chloroplast, for the accumulation of PA1, despite its low abundance there (< 0.001% total cell protein). PMID- 8000432 TI - Inefficient processing of human protein C in the mouse mammary gland. AB - Vitamin K-dependent plasma protein, human Protein C (HPC) has been expressed in transgenic mice, using a 4.2 kb mouse whey acidic protein (WAP) promoter, 9.0 kb HPC gene and 0.4 kb 3' flanking sequences. Expression was mammary gland-specific and the recombinant human Protein C (rHPC) was detected in milk at concentrations of 0.1 to 0.7 mg ml-1. SDS-PAGE revealed that the single, heavy and light chains of rHPC migrated with increased electrophoretic mobility, as compared to HPC. Enzymatic deglycosylation showed that these molecular weight disparities are in part due to differential glycosylation. The substantial increase observed in the amount of single chain protein, as well as the presence of the propeptide attached to 20-30% of rHPC, suggest that mouse mammary epithelial cells are not capable of efficient proteolytic processing of rHPC. The Km of purified rHPC for the S-2366 synthetic substrate was similar to that of plasma-derived HPC, while the specific activity was about 42-77%. Amino acid sequence analyses and low anticoagulant activity of purified rHPC suggest that gamma-carboxylation of rHPC is insufficient. These results show that proteolytic processing and gamma carboxylation can be limiting events in the overexpression of fully biologically active rHPC in the mouse mammary gland. PMID- 8000433 TI - Specific combinations of human serum albumin introns direct high level expression of albumin in transfected COS cells and in the milk of transgenic mice. AB - A new series of expression vectors, each comprised of the beta-lactoglobulin (BLG) promoter driving one of a variety of human serum albumin (HSA) minigenes or the entire gene, were evaluated for their ability to direct expression of HSA in vitro in COS tissue culture cells and into the milk of transgenic mice. Vectors directed a hierarchy of expression levels in vitro, dependent upon the specific complement of HSA introns included. HSA introns acted in a synergistic manner. In addition, minigenes comprised of specific subsets of introns were more efficacious than the entire HSA gene with all of its introns. Transgenic mice expressed as much as 10 mg ml-1 of HSA in their milk. Vectors comprised of specific intron subsets directed levels at 1 mg ml-1 or greater in the milk of 20% of generated transgenics. A statistical correlation between the expression level trend in vitro with the trend of expression in vivo (% which express) at detectable levels (p = 0.0015) and at the level of greater than 0.1 mg ml-1 (p = 0.0156) was demonstrated. A weak correlation existed (p = 0.0526) at in vivo levels of 1 mg ml-1 or greater. These new vectors are expected to direct the production of high levels of HSA in the milk of a large percentage of generated transgenic dairy animals. PMID- 8000434 TI - Visualization and ablation of phenylethanolamine N-methyltransferase producing cells in transgenic mice. AB - We cloned and sequenced the mouse phenylethanolamine N-methyltransferase (PNMT) gene which encodes the enzyme that catalyses the conversion of norepinephrine to epinephrine. The ability of various length sequences flanking the mouse or human PNMT genes to direct expression of reporter genes in transgenic mice was examined. We show that 9 kb of 5' flanking sequences from the cloned mouse PNMT gene can direct expression of the Escherichia coli beta-galactosidase (lacZ) gene to predicted regions of the adrenal, eye and brain in the adult transgenic mouse. The transgene was also expressed during development, in the myelencephalon, adrenal medulla and dorsal root ganglia. PNMT-producing cells were ablated by expression of the diphtheria toxin (DT-A) gene driven by the human PNMT promoter, resulting in abnormalities in the adrenal medulla, eye and testis. The hPNMT8 kb DT-A line presents a model with which to examine the developmental ramifications of deletion of PNMT-producing cell populations from the adrenal medulla and retina. PMID- 8000435 TI - Liver, renal and subcutaneous histopathology in PEPCK-bGH transgenic pigs. AB - Transgenic pigs were created that harboured a phosphoenolpyruvate carboxykinase bovine growth hormone construct (PEPCK-bGH). Four founder animals and two transgenic offspring from one line were evaluated between 6 1/2 and 12 months of age. There was no evidence of severe hepatic or renal lesions in these pigs, which characterised transgenic PEPCK-bGH mice previously described. While glomerular and tubular lesions in kidney sections were not identified in the transgenic pigs, mesangial cell proliferation was observed in two transgenic offspring from a single line. Additionally, glomerular size was significantly increased in four of four puberal transgenic swine when compared to age- and sex matched controls (28.30 +/- 4.1 vs. 14.2 +/- 2.7 x 10(5) microns 3; representing 3 transgenic lines, p < 0.05). Surprisingly, no mature adipocytes were observed in subcutaneous sections obtained in transgenic GH pigs. Histological evaluation of these transgenic pigs further illustrates the requirement for precise control of growth-related genes and their protein products. PMID- 8000436 TI - 21st-century health care: trends and technology. PMID- 8000438 TI - Complying with the SMDA medical device tracking regulations: a clinical engineering responsibility. PMID- 8000437 TI - Nursing research: a new frontier for biomedical engineering. PMID- 8000439 TI - Development of a high-performance multiprobe cryosurgical device. AB - The authors describe the design of the first multiprobe cryosurgical system (AccuProbe system). Compared with prior conventional cryosurgical devices, the new system has the following characteristics: 1) generation of subcooled liquid nitrogen, 2) optional use of up to five independently operated and controlled cryoprobes, 3) use of disposable probes of various sizes and shapes, 4) more accurate placement of the cryoprobes in the lesions due to probe miniaturization (3.4 mm in overall diameter), and 5) higher capacity freezing, which supports more accurate and controllable tissue temperatures. With the use of the newly developed system, numerous cryosurgical procedures, including those in the prostate, brain, and liver, have been successfully performed. PMID- 8000440 TI - Improving material properties by a simple gas-treatment procedure. AB - A simple, easy-to-use, room-temperature gas-treatment procedure improves the surface and bulk physical, chemical, and electrical properties of materials in a number of applications. Water wettability and a number of dielectric properties of various polymers, thin metal films, and porous carbon-based cathodes can be markedly changed by exposure for a few minutes to this gas treatment. This inexpensive technique can be used to chemically modify surface, and even bulk, electrical and physical properties of materials. These changes can then improve device performance. The technique can be easily inserted into ordinary manufacturing procedures. PMID- 8000441 TI - Some biochemical and pharmacological aspects of free radical-mediated tissue damage. AB - Living in aerobic conditions carries a risk of oxidative stress, in connection with free radical deleterious action on tissues and cells. Free radical mechanisms have been implicated in the pathogenesis of many diseases, as well as in host defense against various invading microorganisms. A substantial body of evidence has been reported on free radical involvement in inflammation, ischaemia/reperfusion injury, atherosclerosis and many other pathologies. The aim of this paper is to review selected literature and opinions concerning free radical-induced damage to tissues and to present xenobiotic contribution to oxidative stress. PMID- 8000442 TI - Some central effects of kynurenic acid, 7-chlorokynurenic acid and 5,7- dichloro kynurenic acid, glycine site antagonists. AB - Strychnine-insensitive glycine site is one of a few binding sites of NMDA receptor complex. The aim of these study was to find out whether compounds regarded as glycine antagonists-kynurenic acid (KA), 7-chlorokynurenic acid (7 CKA), 5,7-dichlorokynurenic acid (5,7-DCKA) evoke the effects analogous to those of the NMDA receptor antagonist, CGP 37849 (or MK-801) and/or can modulate the effects of the last compounds in rats. KA (but not 7-CKA, given ip) inhibited electroshock-induced seizures and increased the anticonvulsant effect of CGP 37849. CGP 37849-induced locomotor hyperactivity was enhanced by KA, 7-CKA (icv but not ip) and 5,7-DCKA. D-Amphetamine-induced hyperactivity was inhibited by KA as well as 7-CKA. In monoamine-depleted rats 7-CKA (but not KA) increased the antiakinetic effect of clonidine; the antiakinetic effect of L-DOPA was enhanced by 7-CKA and 5,7-DCKA, but not by KA. KA and 7-CKA did not change the spiperone induced catalepsy but they attenuated the anticataleptic effect of CGP 37849; the studied drugs did not change the anticataleptic effect of MK-801. 7-CKA given icv did not influence the spiperone-induced catalepsy as well as the anticataleptic effect of CGP 37849. In the forced swimming test KA, given once, prolonged (50 mg/kg) or did not change (200 and 300 mg/kg) the immobility time. 7-CKA did not affect the immobility time in this model. When given three times KA (200 mg/kg) and 7-CKA (20 mg/kg) reduced the immobility time; the lower doses of KA and 7-CKA prolonged or did not change the immobility time, respectively. Joint injection with imipramine and KA (or 7-CKA) induced the decrease of immobility time (vs imipramine alone or glycine antagonist alone); in the case of joint injection with citalopram + KA (or 7-CKA), the time of immobility was prolonged or not changed. In conclusion, the obtained results point to similarities between glycine antagonists (kynurenine derivatives) and CGP 37849 and to the possibility of positive cooperation between the NMDA- and glycine-sites antagonists. PMID- 8000444 TI - Studies on the effects of certain 5-HT-3 receptor antagonists on ethanol preference and withdrawal seizures in the rat. AB - We tested how certain antagonists of 5-HT-3 receptors affect ethanol consumption and withdrawal seizures in ethanol-dependent Wistar male rats. Low doses of tropisetron (0.001-0.01 mg/kg ip) and ondansetron (0.00025 mg/kg ip) reduced ethanol consumption and preference. Increased ethanol intake was observed, however, after administration of higher doses of ondansetron (0.125 g/kg ip) and granisetron (0.125-0.25 mg/kg ip). Audiogenic seizures in rats withdrawn from ethanol were attenuated by low doses of tropisetron and ondansetron. PMID- 8000443 TI - The influence of calcium channel blockers on the central action of clonidine. AB - The influence of verapamil, nifedipine and cinnarizine on clonidine-induced hypothermia, spontaneous and explorative motility was investigated in mice. Verapamil 5 and 15 mg/kg, nifedipine 17.5 and 50 mg/kg and cinnarizine 75 and 200 mg/kg (that is 1/30 and 1/10 of LD50 respectively) were injected intraperitoneally. The drugs were given in single doses (1/10 LD50) and in repeated doses (1/30 LD50) during a 10 days course. In acute experiments the drugs were given 60 min before clonidine administration, while in chronic experiments clonidine was given on the 11th day of the experiment. Nifedipine prevents clonidine-induced hypothermia in both the applied doses, verapamil only in a single dose, and cinnarizine in repeated doses. Only repeated administration of nifedipine and cinnarizine weakens the clonidine-induced sedation in the studies of spontaneous motility, and as for nifedipine also in explorative motility. PMID- 8000445 TI - Influence of ketamine and its interactions with morphine and nalbuphine on the level of enkephalins in some parts of the brain and spinal cord. AB - The aim of this paper was to study the influence of ketamine in a dose of 80 or 160 mg/kg ip on the level of leu-enkephalin (LENK) or met-enkephalin (MENK) in some parts of the brain and spinal cord, as well as to examine the interaction of ketamine with morphine or nalbuphine on this effect. The influence of ketamine on enkephalins release into the brain perfusate was also studied. Ketamine decreased the spinal cord enkephalins concentration mainly in cervical and lumbar part. These effect was antagonized by naloxone. Ketamine administered in a higher dose increased LENK release, and decreased the release of MENK into the brain perfusate. Morphine (20 mg/kg ip) increased the level of LENK in the hypothalamus, decreased the concentrations of MENK in the medulla oblongata and in the cervical part of the spinal cord, and increased the level of this neuropeptide in the thoracic part of the spinal cord. These effects were antagonized by ketamine. Ketamine and morphine administered simultaneously affected the level of enkephalins in some of the studied parts of the brain and spinal cord. Nalbuphine administered in doses ranging from 1 to 20 mg/kg changed the level of enkephalins in some parts of the central nervous system. Ketamine and nalbuphine administered simultaneously changed the level of enkephalins in the spinal cord and in the hypothalamus. It is concluded that: the decrease of the level of enkephalins in the spinal cord is an evident feature of ketamine action mediated probably by opioid receptors. Ketamine affects the release of LENK and MENK from the brain in a different way.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8000447 TI - Blood pressure responses to substances interfering with nitric oxide formation, cyclooxygenase and converting enzyme activities and vasopressin V1 receptors blockade in conscious spontaneously hypertensive and normotensive rats. AB - The aim of the study was to investigate to what extent inhibition of nitric oxide (NO) formation, cyclooxygenase and converting enzyme activities and vasopressin V1 receptors blockade affects the cardiovascular system in conscious, freely moving normotensive Wistar-Kyoto (WKY) and spontaneously hypertensive (SHR) rats. The experiments were performed on 33 WKY and on 33 SHR. In series 1 (8 WKY and 8 SHR) animals received bolus injection of N omega-nitro-L-arginine - NLA (10 mg/kg), in series 2 (6 WKY and 6 SHR) bolus injection of indomethacin (10 mg/kg). In series 3 (8 WKY and 8 SHR) the animals received captopril as initial bolus (1 mg/kg) followed by constant infusion (1 mg/kg/min), in series 4 (11 WKY and 11 SHR) vasopressin V1 receptor antagonist 1-(1-mercapto-4-methylcyclohexaneacetic acid)-8-arginine-vasopressin (MeCAAVP) was infused (1.52 micrograms/kg/min). In series 1 in WKY NLA elicited a long-lasting, significant increase in mean blood pressure (max 46 +/- 3 mmHg at 40 min). In SHR mean blood pressure raises were not significant (max 22 +/- 6 mmHg). In series 2, both in WKY and SHR, indomethacin elicited only transient, nonsignificant increases in mean blood pressure. In series 3, the mean blood pressure fall during the captopril infusion was more pronounced in SHR than in WKY (45 +/- 2 mmHg vs 13 +/- 2 mmHg respectively). In series 4 vasopressin V1 receptor blockade caused a nonsignificant fall in mean blood pressure, both in WKY and SHR.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8000448 TI - Prolonged administration of imipramine and (+)-oxaprotiline, but not citalopram, results in sensitization of the rat hippocampal CA1 neurons to serotonin ex vivo. AB - Prolonged (14 days, twice daily), but not acute, application of imipramine and (+)-oxaprotiline (10 mg/kg) induced sensitization of hippocampal CA1 neurons to the inhibitory effect of 5-hydroxytryptamine (5-HT), as studied ex vivo in the rat hippocampal slice preparation. Attenuation of the population spike, recorded in the CA1 pyramidal cell layer in response to stimulation of the Schaffer collateral-commisural pathway, was used to asses the sensitivity of neurons to 5 HT. Prolonged and acute administration of the selective 5-HT reuptake blocker citalopram did not change the responsiveness of hippocampal neurons to 5-HT. Since imipramine and (+)-oxaprotiline share the inhibitory effect on the norepinephrine reuptake, our results may indicate that long-term alterations in the noradrenergic system lead to modifications in postsynaptic serotonergic receptors. PMID- 8000449 TI - Shuttle-box avoidance behavior of mice treated with nifedipine in combination with nicotine or physostigmine. AB - Nicotine and physostigmine, given alone, slightly improved shuttle-box avoidance acquisition in mice. the dihydropyridine calcium channel inhibitor nifedipine, ineffective alone, enhanced the avoidance facilitating action of nicotine, but prevented the slight improving action of physostigmine. The results confirm that calcium channel blockers can interfere with the effects of centrally acting drugs and may augment the facilitation of learning induced by some of them. However, a comparison of the effects of nifedipine with those of the noncalcium antagonist vasodilator hydralazine suggests that hypotensive action of calcium channel blockers may interfere with the behavioral action related to specific neuronal changes due to calcium channel blockade. This may be particularly important in cases in which hypotensive action is exerted by the agent used in combination with the calcium channel blocker. PMID- 8000446 TI - The effect of chronic treatment with antidepressant drugs on the corticosteroid receptor levels in the rat hippocampus. AB - The effect of long-term (28 days) treatment with desipramine, (+)-oxaprotiline (selective inhibitors of the noradrenaline - NA - uptake), citalopram (a selective inhibitor of the serotonine - 5-HT - uptake) and mianserin (an atypical antidepressant drug, devoid of an effect on the monoamine uptake) on the binding parameters of corticosteroid receptors was studied in the rat hippocampus. Glucocorticoid (GR) and mineralocorticoid (MR) receptors were examined by an in vitro [3H]-corticosterone binding in the cytosol from the rat hippocampus, using the selective GR agonist RU 28362 to discriminate between MR and GR. Long-term treatment with desipramine significantly increased the Bmax of GR at both 2 (increase by 42%) and 72 h (increase by 27%) after its last dose, but did not change the Bmax of MR and the Kd of GR and MR. Repeated treatment with (+) oxaprotiline, citalopram and mianserin did not modify the binding parameters of GR and MR. These results indicate that the ability to increase the Bmax of GR is not a common feature of all antidepressant drugs, and that the influence of antidepressant drugs on the GR level is not connected with their action on the uptake of NA or 5-HT. PMID- 8000451 TI - Endogenous drug-like factors in a Polish population. AB - In two hundred and twenty-five healthy volunteers not receiving any treatment the occurrence of drug-like factors in blood serum was studied. The examinations were carried out with the use of the fluorescence-polarization-immunoassay (FPIA)-TDx Abbott. The presence of endogenous phenytoin-like, theophylline-like and cyclosporin-like factors has been demonstrated. PMID- 8000450 TI - Aminooxyacetic acid-induced accumulation of GABA enhances clonidine hypotension. AB - The effect of 2-oxoglutarate aminotransferase inhibitor, aminooxyacetic acid (AOAA) on hypotension induced by clonidine in spontaneously hypertensive rats (SHR) was examined. AOAA given 15 min before clonidine significantly intensified clonidine--induced reduction of blood pressure. This effect reached its maximum within 120 min after AOAA administration, when AOAA itself had no influence on blood pressure. Our data suggest that the activation of functional state of GABAergic system by GABA accumulation potentiates clonidine hypotension. PMID- 8000452 TI - The effect of neonatal immunoregulatory cells and cyclosporine on the heart allograft survival in rats. AB - Lymphoid neonatal cells from syngeneic donors are able to modulate the reactivity of recipient rats to MHC-incompatible vascular cardiac grafts. The suppressor splenocytes, obtained from one-day-old rats, may enhance the immunosuppressive effect of chronically administered low doses of cyclosporine (CsA). PMID- 8000454 TI - The three Rs: reading, writing, and research. PMID- 8000455 TI - Perceptions of collaborative practice between Navy nurses and physicians in the ICU setting. AB - BACKGROUND: Despite strong evidence for the benefits of collaborative practice between nurses and physicians, this model remains the exception rather than the rule. OBJECTIVES: To examine the extent to which Navy nurses and physicians perceive that collaborative practice exists in the ICU, and to examine the difference in perceived use of collaborative practice by Navy nurses and physicians in the ICU. METHODS: Ninety nurses and 49 physicians working in ICUs at the Navy's four teaching hospitals and aboard the Navy's two hospital ships deployed in Southwest Asia were surveyed using the Collaborative Behavior Scale Part I and the Collaborative Practice Scales. RESULTS: There was a significant difference between nurses' and physicians' perceptions of collaborative practice behavior. Physicians reported that collaborative practice behavior existed to a greater extent than did nurses in the study. There was no significant difference between nurses' and physicians' perceived use of collaborative practice behavior. CONCLUSIONS: Navy ICU nurses and physicians perceived that they were involved in collaborative practice behavior at a moderate level. Physicians, however, reported perceiving collaborative practice to a greater extent than did nurses. Further research, in different populations, is required to test the theorized constructs of the instruments used to measure perceptions of collaborative practice behavior in this study. PMID- 8000453 TI - Pharmacological modulation of glucocorticoid and mineralocorticoid receptors in the rat central nervous system. AB - This review examines neurochemical mechanisms of the corticosteroid receptor regulation in the central nervous system. Glucocorticoid (GRs) and mineralocorticoid (MRs) receptors are localized in discrete brain regions, especially in the limbic system, and exert inhibitory control over the hypothalamic-pituitary-adrenal (HPA) axis; moreover, they are found to affect the responsiveness of neurotransmitters. The GR and MR levels and biosynthesis appear to be under a serotoninergic and, to a lesser extent, a noradrenergic, cholinergic and dopaminergic influence. Of the neuropeptides studied, vasopressin and ACTH regulate the corticosteroid receptor density. The above data strongly suggest that GR and MR may be affected by some psychotropic drugs which are known to cause alterations in classic neurotransmitter systems. In this respect, adaptive changes in GR and MR parameters, evoked by drugs which are commonly administered for a long time, e.g. antidepressants or drugs of abuse, seem to be of particular interest. Long-term treatment with tricyclic antidepressants such as imipramine, desipramine, amitriptyline and maprotiline elevates the density and/or biosynthesis of GR and/or MR. Similar effects are observed after chronic lithium or repeated electroconvulsive shock (ECS), which suggests that alterations in corticosteroid receptors may be involved in the mechanism of their antidepressant action. On the other hand, chronic administration of drugs of abuse, such as amphetamines or morphine, down-regulates GR which may impair the feedback control mechanism of the HPA activity. PMID- 8000456 TI - Adult respiratory distress syndrome: outcome in a community hospital. AB - BACKGROUND: Published reports indicate that survival rates of patients with adult respiratory distress syndrome have not improved dramatically since the first report of the condition in 1967. However, changes in ventilator strategies and improved critical care management may result in better survival rates in patients with well-defined, severe adult respiratory distress syndrome. OBJECTIVES: To report the outcomes of patients with adult respiratory distress syndrome treated in a community hospital and compare these findings with those in previously published reports. METHODS: A retrospective study design was used. All patients diagnosed with adult respiratory distress syndrome (N = 47) over a 2-year period were studied. RESULTS: For the study patients, the survival rate was 64%; 29% died from respiratory failure alone. Analysis demonstrated that advanced age was not associated with mortality. Pressure-control ventilation was used for 31 patients and there was no significant difference in the presence of barotrauma in the pressure-control mode vs volume ventilation. CONCLUSION: This survival rate exceeds most recently reported rates and thus supports the idea that improvement in treatment of adult respiratory distress syndrome is occurring. PMID- 8000457 TI - Comparison of five clinical weaning indices. AB - BACKGROUND: Despite extensive data acquired in the area of weaning, clinicians still struggle with the questions of how and when to begin the process. Clinical weaning indices, designed to predict weaning potential, are often difficult to use. They provide an answer at a specific time; extrapolation to the weaning process is rarely possible. No single index has proven to be superior. OBJECTIVES: To test the efficacy of five clinical weaning indices (Burns Weaning Assessment Program; Weaning Index; frequency tidal volume ratio; compliance, resistance, oxygenation and pressure index; and negative inspiratory pressure) at regular intervals during withdrawal of ventilatory support and to determine threshold levels for the program. METHODS: A prospective convenience sample consisted of 37 adult critical care patients requiring mechanical ventilation for at least 7 days and identified as stable and ready to wean. Data were collected on all weaning indices every other day until the patient was weaned. RESULTS: With the exception of the Burns Weaning Assessment Program, weaning indices did not change significantly from preweaning scores. Furthermore, the results failed to demonstrate that any of the five clinical weaning indices have strong predictive power related to weaning trial outcomes, although all the indices had negative predictive values that may be helpful in predicting unsuccessful weaning trials. CONCLUSIONS: The results of this study suggest that the process of weaning may be enhanced by comprehensive, systematic approaches and that clinical weaning indices like the Burns Weaning Assessment Program might best serve as tools to track trends in progress, keep care planning on target, and prevent unsuccessful weaning trials. PMID- 8000458 TI - Comparison of SVO2, SpO2, and clinical parameters with arterial blood gases during ventilatory weaning after cardiac surgery. AB - Correlations of mixed venous and arterial oxygen saturation, heart rate, respiratory rate, and mean arterial pressure with arterial blood gas variables were computed for 57 sets of data obtained from 30 postoperative coronary artery bypass graft patients who were being weaned from mechanical ventilation. Arterial oxygen saturation and respiratory rate correlated significantly, although moderately, with blood gases. PMID- 8000459 TI - Shivering following cardiac surgery: predictive factors, consequences, and characteristics. AB - BACKGROUND: Shivering is common after cardiac surgery and may evoke harmful hemodynamic changes. Neither those changes nor factors increasing probability of shivering are well defined. OBJECTIVES: (1) To identify factors linked with risk of shivering by comparing age, weight, body surface area, gender, intraoperative details, anesthetics, postoperative temperatures, hemodynamics, and therapeutics in shivering vs nonshivering patients. (2) To describe temperatures, hemodynamics, therapeutics, myocardial oxygen consumption correlates (rate pressure product, heart rate, systemic vascular resistance) in shivering and nonshivering groups, and shivering and nonshivering periods. (3) To characterize the electromyogram to determine whether the tremor is cold-induced. METHODS: A descriptive design with a time series component was used to study a convenience sample of 10 shivering and 10 nonshivering adults for 4 hours during early recovery from cardiac surgery. Pulmonary artery and skin (facial, calf, trunk) temperature were measured every 60 seconds; heart rate and arterial pressure, every 15 minutes; cardiac output, 3 times. Electromyogram was recorded intermittently. Medications and treatments were noted. RESULTS: Lower skin temperature was significantly related to shivering risk. Heart rate was significantly higher initially in shiverers and remained higher by 13.6 beats per minute. Significantly more nitroprusside was used to control arterial pressure before than after shivering. No significant differences were noted between groups in core temperature, age, weight, body surface area, anesthesia type, intraoperative temperature; or surgery, circulatory bypass, or cardiac cross clamp duration. The electromyogram pattern during shivering was typical of that produced by cold. CONCLUSIONS: These results suggest that true shivering occurs after cardiac surgery. Skin, but not core, temperature and elevated heart rate predict shivering. Shivering may be more likely in hemodynamically unstable patients. PMID- 8000460 TI - Patients' reactions to angioplasty: realistic or not? AB - BACKGROUND: A major problem limiting the success of angioplasty is the high restenosis rate. In addition, coronary artery disease is an ongoing process requiring lifestyle changes to prevent disease progression. OBJECTIVE: To examine patient concerns and risk factor modification behaviors during early recovery from angioplasty. Specific attention was directed to: (1) expectation of restenosis, (2) occurrence of angina, (3) achievement of expected benefits, (4) tension/anxiety levels, (5) self-efficacy for and actual performance of needed lifestyle changes. METHODS: For this descriptive study the Self-Report of Recovery (a project-derived questionnaire) and the Profile of Mood States were mailed to 54 patients at 1, 6, and 12 weeks of recovery. The study group comprised 37 men and 17 women (mean age, 57 years) who had undergone first-time successful angioplasty at a midwestern medical center. At 12 weeks 78% remained. RESULTS: A majority of patients did not expect restenosis to occur. At 3 months 83% reported that they were angina-free, 90% reported that they would repeat the procedure if needed, all scores on the tension/anxiety scale were normal, and 86% had achieved some benefits they had expected. Most expressed high confidence in their ability to reduce risk factors, with 90% reporting initiation of at least one lifestyle change. CONCLUSION: We concluded that patients had positive feelings about their angioplasty experience and were not overly concerned about restenosis. PMID- 8000461 TI - Effects of bathing, passive range-of-motion exercises, and turning on oxygen consumption in healthy men and women. AB - BACKGROUND: Baseline data are needed to provide a foundation for future studies investigating the effects of various nursing interventions on the oxygen requirements of critically ill patients. OBJECTIVES: To establish reference values for the oxygen requirements of adults in response to three common patient events: a nurse-administered bed bath, passive range-of-motion exercises, and turning from side to side; and to determine whether the order in which the interventions were administered had an effect on oxygen consumption. METHODS: A convenience sample of 30 healthy men and women were randomly assigned to one of three treatment groups, for which the order in which interventions were to be administered had previously been designated. Data were analyzed using analysis of variance with repeated measures. RESULTS: There was a significant difference in the mean oxygen consumption among activities, as well as between men and women, with men having a significantly higher mean oxygen consumption than that of the women. For both men and women, the mean oxygen consumption during unassisted turning and back care was significantly higher than at baseline. The oxygen consumption for men averaged 4.25 mL/kg per minute, SD = .71 at baseline, 5.08 mL/kg per minute, SD = .98 for turning, and 4.72 mL/kg per minute, SD = .90 during back care. Women averaged 3.74 mL/kg per minute, SD = .49 at baseline, 4.48 mL/kg per minute, SD = .85 for turning, and 3.89 mL/kg per minute, SD = 1.15 during back care. Changes in oxygen consumption for other interventions were nonsignificant and negligible. Oxygen consumption returned to near baseline within 15 minutes of cessation of activity. The order in which interventions were administered did not have a significant effect on oxygen consumption. CONCLUSIONS: The anterior bath and passive range of motion exercises have minimal effect on oxygen consumption. Turning and back care significantly increase oxygen consumption from the baseline value. The order in which interventions are administered does not have any appreciable effect on oxygen consumption. PMID- 8000462 TI - The effect of Trendelenburg and modified trendelenburg positions on cardiac output, blood pressure, and oxygenation: a preliminary study. AB - BACKGROUND: Although we have insufficient knowledge about the effects of Trendelenburg positions on various hemodynamic parameters, these positions are frequently used to influence cardiac output and blood pressure in critically ill patients. OBJECTIVES: To determine the effect of Trendelenburg and modified Trendelenburg positions on five dependent variables: cardiac output, cardiac index, mean arterial pressure, systemic vascular resistance, and oxygenation in critically ill patients. METHODS: In this preliminary study subjects were 23 cardiac surgery patients (mean age, 55; SD, 8.09) who had a pulmonary artery catheter for cardiac output determination and who were clinically stable, normovolemic and normotensive. Baseline measurements of the dependent variables were taken in the supine position. Patients were then placed in 10 degrees Trendelenburg or 30 degrees modified Trendelenburg position. The dependent variables were measured after 10 minutes in each position. A 2-period, 2 treatment crossover design with a preliminary baseline measurement was used. RESULTS: Five subjects were unable to tolerate Trendelenburg position because of nausea or pain in the sternal incision. In the 18 who were able to tolerate both position changes, no statistically significant changes were found in the five dependent variables. Changes in systemic vascular resistance over time approached statistical significance and warrant further study. CONCLUSIONS: This preliminary study does not provide support for Trendelenburg positions as a means to influence hemodynamic parameters such as cardiac output and blood pressure in normovolemic and normotensive patients. PMID- 8000463 TI - Comparison of blood glucose levels in the cardiac surgical patient. PMID- 8000464 TI - Mycobacterium tuberculosis in persons infected with the human immunodeficiency virus. AB - BACKGROUND: After decades of decreasing incidence, the number of new tuberculosis cases started to rise again in the mid-1980s and continues to be a major public health problem in the United States. The incidence of tuberculosis and drug resistant tuberculosis is increasing among persons infected with human immunodeficiency virus. OBJECTIVE: To review the epidemiology, pathogenesis, clinical presentation, diagnosis, drug therapy, patients' nonadherence to prescribed treatment, and nursing issues related to the care of persons dually infected with tuberculosis and human immunodeficiency virus. METHODS: Fifty references addressing important issues in tuberculosis and human immunodeficiency virus were identified by searching the Medline data base and bibliographies of relevant articles. DISCUSSION: Tuberculosis is a communicable infectious disease caused by Mycobacterium tuberculosis. It is curable and preventable but generally fatal if undiagnosed and untreated. People with human immunodeficiency virus infection are at higher risk for reactivation of latent tuberculosis infection and for developing life-threatening tuberculosis. Specific nursing interventions are formulated to guide practice when caring for HIV-infected persons with tuberculosis. Future nursing research needs are suggested. CONCLUSIONS: An understanding of the complexity of the care involved will enhance the clinical management of tuberculosis in human immunodeficiency virus-infected patients and lead to a decline in the appearance of new drug-resistant tuberculosis strains. PMID- 8000465 TI - Estrogen replacement therapy in women: prevention and treatment of coronary artery disease. PMID- 8000466 TI - Care: antidote for nurses' love-hate relationship with technology. PMID- 8000468 TI - Need for nursing research in the area of improving communication for mechanically ventilated patients. PMID- 8000467 TI - Critical care nurse practitioners. PMID- 8000469 TI - The couvade syndrome. AB - The couvade syndrome can be considered to be the psychosomatic equivalent of primitive rituals of initiation into paternity. Various symptoms have been described in the husbands of pregnant women with an incidence from 11% to 65%. The most common of these are: variations in appetite, nausea, insomnia and weight gain. Seventy-three couples with the women in the last month of pregnancy were given a questionnaire; as a reference group, 73 men without pregnant wives or children under 1 year of age were taken. An emotional involvement connected with pregnancy was reported in 91.78% of the men. This involvement was expressed as changes in sexual habits in 87.67% of cases, fear and anxiety in 36.98% and curiosity in 47.94%. With the exception of nausea, physical symptoms were less frequent in the men with pregnant wives than in those without pregnant wives. These data cannot confirm the existence of the couvade syndrome with its own physical symptoms but we think that some male experiences, which constitute a peculiar imaginary and behavioral reality of the father-to-be, do exist. PMID- 8000470 TI - Early loss of parents and early rearing experience among women with antenatal depression. AB - The relationship of depressive disorders with early parental losses and rearing experiences was studied among 120 pregnant women. They were diagnosed following the Research Diagnostic Criteria using the Schedule for Affective Disorders and Schizophrenia. Loss experience was defined either as loss of a parent before the age of 16 by death, or separation for 12 months or longer. The perceived rearing experience was examined by administering the Parental Bonding Instrument (PBI). An onset of depressive disorders, antenatal depression, was observed among 19 (16%) women. Those women with antenatal depression were significantly more likely to have experienced bereavement of either of the parents (21%) than those women without it (5%). Discriminant function analysis revealed that two PBI scores, lower paternal care and higher maternal protection, were significant in predicting antenatal depression. Parental bereavement and 'affectionless control' (low care and overprotection) seem to be additive in predisposing to antenatal depression, though the small number of the samples render statistical analysis impracticable. PMID- 8000471 TI - Postpartum mental health. AB - The mental health of parturients 1-2 months after delivery was assessed. The study was carried out using a questionnaire between September and November 1992 in connection with the postpartum visits of mothers to the maternity health care center. The need for psychological help was assessed using a 12-item questionnaire (General Health Questionnaire), according to which 28% of the subjects needed psychological help. These mothers did not differ from the others in terms of age, marital status, education, or financial situation. Nor was the need for psychological help associated with health habits, with traumatic life events or conflicts during childhood and adolescence, or with delivery-related factors. Mothers needing psychological help were more depressed and considered the social support they were receiving to be inadequate more often than the others. These women also more often reported marital problems during pregnancy and after delivery. None of the mothers had sought help because of mental health problems. It is concluded that antenatal and postnatal clinics should pay more attention to the mental health of mothers. PMID- 8000472 TI - A researcher's guide to investigating the psychological sequelae of infertility: methodological considerations. AB - Research into the psychological sequelae of infertility has been plagued by a number of methodological problems. The most common methodological concerns involve conceptual confusion regarding the measurement and existence of psychiatric morbidity among the infertile, selection of convenience samples which limit generalizability, and failure to analyze the influence of important variables like diagnosis, treatment length, dyadic concordance and dyadic patterns. These methodological limitations are detailed and recommendations are made for future research. PMID- 8000473 TI - Factors influencing the well-being of long-term infertile couples. AB - The aim of the study was to investigate factors that may influence the well-being of long-term infertile couples. One hundred and eight childless couples with a long-term infertility completed a structured questionnaire. Three groups of independent variables were discerned: sociodemographic factors, factors associated with infertility and the desire to have a child, and personality characteristics. The effect of these variables upon seven dimensions of (negative) well-being: depression, anxiety, hostility, health complaints, guilt/blame, self-esteem and sexuality was investigated. Strong negative feelings concerning infertility and a high degree of femininity were associated with a low level of well-being (among women as well as among men). To a lesser extent, secrecy with regard to infertility and being the infertile partner (among men) and still pursuing medical treatment (among women) were related to a lower sense of well-being. Recognition of these relations may help in the counselling of infertile couples. PMID- 8000474 TI - Personality characteristics of stress incontinent women: a pilot study. AB - Personality traits were assessed by means of the Karolinska Scale of Personality (KSP) and the Eysenck Personality Inventory (EPI) in 45 genuine stress incontinent women and compared with a reference group of continent women in order to investigate the possible impact of this chronic condition on the personality. Women with stress incontinence of long duration scored significantly higher than controls on the KSP scales somatic anxiety, psychic anxiety, psychasthenia and suspicion and on the EPI lie-scale. These findings point to the importance of personality factors in chronic conditions such as urinary incontinence. PMID- 8000475 TI - Symptom perception: psychological correlates of symptom reporting and illness behavior of women with medically unexplained gynecological symptoms. AB - Medically unexplained (gynecological) symptoms can be viewed as an indication of the somatization of negative emotions. Most studies regarding psychological correlates of medically unexplained gynecological symptoms have paid attention only to certain personality characteristics of women with these symptoms. In this study the reporting of physical symptoms and the resulting illness behavior is explained in terms of information processing or a perception process, i.e. the process by which people detect and interpret physical sensations as symptoms of illness (symptom perception). Symptom perception is in part determined by environmental characteristics and cognitive and emotional processes, such as variation in daily life, (coping with) emotional threat and the use of cognitive illness schemes. Differences in symptom perception and illness behavior of women with medically unexplained and explained gynecological symptoms, compared to women with medically explained gynecological symptoms and a control group, were established with the help of a questionnaire, containing a number of scales. As expected, women with medically unexplained gynecological symptoms had higher reports of common symptoms and sensations and showed also more other illness behavior than the other two groups. They reported less variation and more threat in daily life than the other two groups. These variables together with the use of illness schemes contributed most to symptom reporting of women with medically unexplained symptoms. It is concluded that defence against threat is probably an important determinant. Suggestions for further research and some practical implications are discussed. PMID- 8000476 TI - Establishment of a pluripotent cell line derived from a medaka (Oryzias latipes) blastula embryo. AB - A pluripotent cell line, OLES1, was established from a blastula embryo of a small freshwater fish, medaka (Oryzias latipes). Cells of this cell line were small and round, and they grew actively and stably in culture as dense clusters. They exhibited a positive alkaline phosphatase activity upon histochemical staining. When the cells were treated with retinoic acid, differentiation into various types of cells, including melanocytes, dopa-positive precursors of melanocytes, and cells with a molecular marker of skeletal muscles, troponin T, was induced in vitro. The present study opens a way to establishing embryonic stem cell lines in fish. PMID- 8000477 TI - An efficient expression vector for transgenic medaka construction. AB - The transparency and external fertilization of the eggs of medaka (Oryzias latipes) make them ideally suitable for investigating molecular interactions that occur during vertebrate development. Genetically engineered medaka is a potential tool for such studies. It requires several types of suitable expression vectors. To obtain abundant and ubiquitous expression of foreign genes in medaka embryos, we have designed an expression vector that contains the proximal promoter and enhancer elements and polyadenylation signal of the medaka beta-actin gene. The utility of this "all-medaka" expression vector was examined using the Escherichia coli lacZ gene as a reporter gene. Most of the injected embryo showed high gene expression, and several embryos showed ubiquitous expression even at six days after injection. Of nine individuals derived from the injected embryos and grown until adult stage, one produced expression-positive F1 fish. The transgene was identified in these F1 using polymerase chain reaction (PCR). These data revealed that the expression vector based on the expression cassette from the medaka beta actin gene should be useful for making transgenic medaka. The cloned gene in this cassette vector is stably transmittable and efficiently expressible. PMID- 8000478 TI - M13 DNA fingerprinting in differentiation of marine Vibrio species. AB - The identification and differentiation of bacterial strains and species are frequently carried out by the use of diagnostic biochemical profiles, serology, and the detection of restriction fragment length polymorphisms in genomic DNA. We show here that DNA restriction fragment length polymorphisms detected using a probe derived from bacteriophage M13 can discriminate between several marine Vibrio species. We have also demonstrated that individual isolates of Vibrio species can be differentiated using the M13 probe. PMID- 8000479 TI - Cloning and sequencing of the Atlantic salmon (Salmo salar) cytochrome c oxidase subunit III gene (coxIII) and analysis of coxIII expression during parr-smolt transformation. AB - Smoltification is the process whereby salmon alter their metabolism in preparation for movement from freshwater to seawater. Differential screening of a cDNA library prepared from post-smolt salmon liver mRNA led to the selection of a smoltification-induced sequence. Analysis of this cDNA revealed that it partially encoded subunit III of the enzyme cytochrome c oxidase. The complete coxIII sequence was amplified from salmon genomic DNA using consensus oligonucleotides based on ATPase 6 and tRNA(GLY) sequences from Pacific salmonid species. Cytochrome c oxidase subunit III liver mRNA levels were found to be significantly increased in salmon smolts. Northern blot analysis revealed a coxIII transcript of approximately 750 bp in all salmon tissues tested except blood. The DNA sequence of coxIII employs the mammalian mitochondrial genetic code and is strongly conserved when compared with that of other species. PMID- 8000480 TI - Parasexual crosses and hybrid selection with a near haploid variant of the epithelioma papulosum cyprini, cell line EPC: a tissue culture model for the analyses of dominance, recessiveness, and complementation of mutant phenotypes. AB - We describe techniques for insertional mutagenesis of tissue-cultured piscine cells in which we use transfection with G418 and hygromycin B resistance conferring plasmids, cell matings by electrofusion, and positive selections of fusion hybrids by dual challenge with the antibiotics G418 and hygromycin B. These techniques are designed to facilitate genetic and molecular analyses of tissue-cultured cells. The experiments were conducted with EPC-1, a new variant of the carp epithelioma cyprini cell line. EPC, with a near haploid number of chromosomes, EPC-1 retains cell morphology and growth characteristics of EPC, including anchorage independence, but shows a higher degree of contact inhibition. The number of metaphase chromosomes of EPC-1 is 53, as opposed to 96 reported for EPC. PMID- 8000481 TI - Cleveland health quality choice: a model for collaborative community-based outcomes assessment. AB - BACKGROUND: Cleveland Health Quality Choice Coalition was established in 1989 as a voluntary, collaborative effort between hospitals, physicians, and purchasers in the Cleveland metropolitan area to assess the quality and efficiency of care in 31 hospitals. The objective of the project is to produce high-fidelity comparative hospital outcomes data that support market-based health care reform strategies. METHODS: The project reports on a broad spectrum of hospital outcomes, including patient satisfaction, in-hospital mortality, length of stay, hospital-acquired complications, and cesarean section rates for adult medical, surgical, obstetrical, and intensive care patients. Intensive care outcomes and patient satisfaction are assessed using previously validated measurement systems. Outcomes for medical, surgical, and obstetrical patients are examined using a standardized data collection and severity adjustment methodology developed by Cleveland physicians and an independent consultant. RESULTS: The project released its initial report to purchasers in April 1993, with subsequent reports scheduled for release every six months. Several policies, procedures, and programs have been instituted to ensure data quality and participant buy-in. These include initial testing and rigorous validation of all outcomes measurement systems before release of data, a commitment to continuously refine risk-adjustment methodologies, independent auditing of data reliability, and a series of user training workshops for project participants and local news media. CONCLUSION: The early success of Cleveland Health Quality Choice Coalition demonstrates that it is possible for purchasers and providers to cooperatively assess the quality of health care on a regional basis and to institute a market-based strategy for health care reform. Further evaluation is needed to determine how performance data being reported are used by purchasers in selecting health care and by hospitals for quality improvement. PMID- 8000482 TI - Evaluating a patient satisfaction survey for maximum benefit. AB - BACKGROUND: Patient satisfaction surveys are now in use in some form at most hospitals and health care systems. Yet, it is unclear how well information collected meets the needs of all groups who might benefit from patient feedback. An evaluation was conducted at the Center for Outcomes Research, Sisters of Providence Health System (Portland, Ore), to determine the extent to which the survey, then almost three years in use, was satisfying its internal consumers and to guide redesign of the entire survey process. METHOD: The evaluation of the survey process was designed to address several questions: who uses the results (consumers); what are their objectives (goals); what results are useful (product); and what is done with the results (intervention utility). Techniques such as interviews, literature reviews, and supplemental data collection, were used to explore the needs of each consumer group. CONCLUSION: The evaluation has led to a number of changes in the patient satisfaction survey process. Large scale patient satisfaction surveys result in large-scale costs and therefore must be beneficial to multiple users in multiple ways. PMID- 8000483 TI - Implementing TQM in a military hospital in Saudi Arabia. AB - BACKGROUND: Health care services in the Kingdom of Saudi Arabia are unique not only in the varied patient population served and multinational staff recruited to provide services, but also because they are not driven by financial or medicolegal constraints. As part of a five-year plan (carried out in four phases) to improve the quality of health care provided in the Kingdom, the North West Armed Forces Hospitals (NWAFH) in Tabuk became the first health care facility in the Kingdom to implement total quality management (TQM). This was not an implementation de novo, but a well-coordinated transition from quality assurance (QA) to TQM. The hospital leadership believe that TQM is best implemented when there is a strong foundation of QA to provide a pre-existing process for data collection and performance measurement. METHODS: Using the eight-step model for implementing TQM adapted from Joint Commission standards and The Health Care Manager's Guide to Continuous Quality Improvement, the QA staff identified the customers of the QA department, their needs, and professional requirements; implemented changes to meet these needs; identified internal monitors to evaluate the effectiveness of the operational changes and monitor performance; reported results and identified opportunities for improvement; and problem solved with FOCUS-PDCA. RESULTS: These efforts yielded a customer satisfaction survey in the form of a report card. In addition, three case studies launched by the QA department to address abstract data accuracy and completion, nosocomial infection rates in cesarean-section patients, and receipt of hospital laboratory reports by peripheral clinics are described in detail. CONCLUSION: The NWAFH Program leadership believes that TQM is a pancultural concept and that these first successful efforts can provide a model for the expansion of TQM not only in Saudi Arabia but throughout the rest of the Middle East. PMID- 8000484 TI - How good are medicine's new recipes? The kitchen debate continues. PMID- 8000485 TI - Is quality being forgotten in health system reform? PMID- 8000486 TI - Quality of care issues for health care reform. PMID- 8000487 TI - Survey of methods and statistical models used in the analysis of occupational cohort studies. AB - OBJECTIVES: This survey was conducted to determine the frequency with which different data analysis techniques are being used in occupational cohort studies. Of particular interest was the relative use of external and internal comparison groups, and the choice of multivariable model. METHODS: Occupational cohort studies published in 1990-91 were located with Medline and Index Medicus, and the contents of several relevant journals were systematically reviewed. Each study was categorised by the methods of external or internal comparisons performed. RESULTS: Of 200 occupational cohort studies identified, 104 (52%) conducted only external comparisons, 46 (23%) conducted only internal, and 50 (25%) presented both. Of those that used an external referent population, about two thirds used a national standard. 40 of the studies that performed internal comparisons fitted multivariable models, with use divided about equally between proportional hazards regression, Poisson regression, and logistic regression. DISCUSSION: The finding that logistic regression is used quite commonly, even though it does not directly model time dependent data of the type frequently encountered in occupational cohort studies, was suprising. The reasons why investigators choose from among the available statistical and modelling techniques are likely to include familiarity, ease of use, restrictions in study population characteristics, especially study size, and others. Authors should be encouraged to be more explicit about the statistical methods used in the analysis of occupational cohort studies, as well as whether important assumptions about their data have been evaluated. PMID- 8000488 TI - Dental health in workers previously exposed to mercury vapour at a chloralkali plant. AB - OBJECTIVES: The dental health of 73 workers previously exposed to mercury vapour at a chloralkali plant was studied and compared with that of 51 non-exposed referents. METHODS: A record of oral, periodontal, gingival and mucosal conditions, including teeth, restorations, prostheses, and oral hygiene, was established during a 30 min examination. The participants' periodontal conditions were assessed according to the community periodontal index of treatment needs (CPITN). The results with the CPITN index were also compared with previously published data for another similar population. RESULTS: There was no significant difference between the exposed workers and the referents with respect to the number of remaining teeth, amount of amalgam restorations, crowns, bridges, or endodontically treated teeth. The oral hygiene among the exposed workers was significantly better than among the referents, but the periodontal health conditions did not significantly differ between the two groups, nor from those of another Norwegian population. DISCUSSION: The present results seem to contradict previous reports claiming tooth loss as a possible result of exposure to mercury vapour. PMID- 8000489 TI - Longitudinal study of workers exposed to mercury vapour at low concentrations: time course of inorganic and organic mercury concentrations in urine, blood, and hair. AB - Seven Japanese female workers exposed to mercury vapour at a concentration of < 0.02 mg Hg/m3 (8 h/day, 44 h/week) were examined for inorganic (I-Hg) and organic (O-Hg) mercury concentrations in urine, blood, and hair after 0, 4, 8, 17, and 23 months of exposure. Both I-Hg and O-Hg concentrations in urine and hair did not increase significantly even after 23 months of exposure. The concentration of I Hg and O-Hg in plasma and O-Hg in erythrocytes, however, increased significantly after four months of exposure, and the high concentrations were maintained until the end of the study (23 months of exposure). Absence of a significant increase in the concentration of O-Hg in hair indicates that changes in concentrations of I-Hg and O-Hg in blood could be caused by the occupational exposure to mercury vapour. These results show clearly that mercury concentration in blood indicates the uptake of mercury compared with data from before employment with mercury. Even after 23 months of exposure to mercury vapour, however, urinary mercury concentration was not affected. PMID- 8000490 TI - Use of molecular epidemiological techniques in a pilot study on workers exposed to chromium. AB - OBJECTIVES: Molecular epidemiological techniques, capable of detecting damage to DNA, were used to see if such damage occurred in the lymphocytes of a group of workers exposed to chromium. The two aims of this pilot study were to see if these new techniques might make useful biological monitoring tools for workers exposed to chromium and also, to help assess whether the current occupational exposure limit for chromium (VI) was sufficiently protective in this specific working situation. METHODS: Volunteer groups of 10 workers exposed to chromium and 10 non-exposed workers provided urine and blood samples towards the end of the working week. Chromium concentrations were measured in whole blood, plasma, lymphocytes, and urine. Lymphocytes were used to examine two forms of DNA damage in the two groups; these were the level of DNA strand breakage and, the production of 8-hydroxydeoxyguanosine. RESULTS: Chromium concentration in whole blood, plasma, and urine of workers exposed to chromium was significantly raised (P < 0.01) compared with non-exposed controls, but in isolated lymphocytes, there was only a modest but significant (P < 0.05) increase in chromium in the group exposed to chromium. There was no difference in the levels of DNA strand breaks or 8-hydroxydeoxyguanosine between the groups. Air monitoring for chromium was not undertaken but current levels for the group exposed to chromium were reported to be around 0.01 mg/m3, which is 20% of the current United Kingdom occupational exposure limit. CONCLUSIONS: We were unable to detect any damage in lymphocytic DNA due to exposure to chromium. This may have been due to the low chromium exposure (< 20% of the United Kingdom occupational exposure limit), the ability of plasma to detoxify chromium (VI) to chromium (III) before it reached the lymphocytes, or perhaps the insensitivity of the molecular techniques used. It is now important to test these and other such techniques on groups exposed to levels closer to the United Kingdom occupational exposure limit. PMID- 8000491 TI - Comparison of measures of lead exposure, dose, and chelatable lead burden after provocative chelation in organolead workers. AB - OBJECTIVES: To describe 6 h urinary lead excretion (6 h PbU) after 1 g intravenous ethylene diamine tetraacetic acid (EDTA) in organolead manufacturing workers with mixed exposure to organic and inorganic lead; to determine the predictors of lead excretion (PbU); and to determine the extent to which internal lead stores and ongoing external exposure govern blood concentrations of lead (PbB). METHODS: A case series of 21 active workers were studied. Personal industrial hygiene data, grouped by 29 exposure zones, in combination with personal interviews about work location and times were used to derive several measures of recent and cumulative exposure to organic and inorganic lead. The average exposure intensities assigned to the 29 zones ranged from 4 to 119 micrograms/m3 (0.02-0.57 mumol/m3 as lead) for organic lead and from 1 to 56 micrograms/m3 (0.004-0.27 mumol/m3) for inorganic lead. RESULTS: After controlling for age, 6 h PbU was significantly and positively correlated with summary measures of PbB--for example, lifetime peak PbB, time weighted PbB--and zinc protoporphyrin concentrations--for example, lifetime peak zinc protoporphyrin, time weighted zinc protoporphyrin--but not with measures of estimated external exposure--for example, duration of exposure and cumulative exposure to inorganic or organic lead. Among workers with higher chelatable lead burdens (6 h PbU > or = 212.4 micrograms (1.03 mumol) divided at the median), there was no apparent relation between recent inorganic lead exposure and PbB at the time of chelation. Among workers with lower chelatable lead burdens (6 h PbU < 212.4 micrograms (1.03 mumol) however, there was a significant relation between exposure and effect between recent exposure to inorganic lead and PbBs. CONCLUSION: These findings are consistent with the concept of physiological dampening. The high chelatable lead burden, a source of internal exposure, dampens the effect of external exposure on PbBs. The data suggest that in organolead workers with high chelatable lead burdens, PbBs may be more influenced by internal lead stores than by variations in airborne exposure to organic and inorganic lead. PMID- 8000492 TI - Mortality of Sardinian lead and zinc miners: 1960-88. AB - The mortality of 4740 male workers of two lead and zinc mines was followed up from 1960 to 1988. Exposure to respirable dust was comparable in the two mines, but the median concentration of silica in respirable dust was 10-fold higher in mine B (12.8%) than in mine A (1.2%), but the mean annual exposure to radon daughters in underground workplaces differed in the opposite direction (mine A: 0.13 working levels (WL), mine B: 0.011 WL). Total observed deaths (1205) were similar to expected figures (1156.3) over a total of 119 390.5 person-years at risk. Underground workers of mine B had significant increases in risk of pulmonary tuberculosis (SMR 706, 95% confidence interval (95% CI) 473-1014) and non-malignant respiratory diseases (SMR 518; 95% CI 440-1606), whereas the only significant excess at mine A was for non-malignant respiratory diseases (SMR 246; 95% CI 191-312). Total cancer and lung cancer mortality did not exceed the expectation in the two mines combined. A 15% excess mortality for lung cancer, increased up to an SMR 204 (95% CI 89-470) for subjects employed > or = 26 years, was, however, found among underground workers in mine A who on the average experienced an exposure to radon daughters 10-fold higher than those of mine B. By contrast, despite their higher exposure to silica, mine B underground workers experienced a lower than expected lung cancer mortality. A ninefold increase in risk of peritoneal and retroperitoneal cancer combined was also found among underground workers of mine A (SMR 917; 95% CI 250-2347; based on four deaths). A causal association with workplace exposures is unlikely, however, as the SMR showed an inverse trend by duration of employment. These findings are consistent with low level exposure to radon daughters as a risk factor for lung cancer among metal miners. Exposure to silica at the levels estimated for the mine B underground environment did not increase the risk of lung cancer. PMID- 8000493 TI - Effect of air humidification on the sick building syndrome and perceived indoor air quality in hospitals: a four month longitudinal study. AB - The sensation of dryness and irritation is essential in the sick building syndrome (SBS), and such symptoms are common in both office and hospital employees. In Scandinavia, the indoor relative humidity in well ventilated buildings is usually in the range 10-35% in winter. The aim of this study was to evaluate the effect of steam air humidification on SBS and perceived air quality during the heating season. The study base consisted of a dynamic population of 104 hospital employees, working in four new and well ventilated geriatric hospital units in southern Sweden. Air humidification raised the relative air humidity to 40-45% in two units during a four months period, whereas the other two units served as controls with relative humidity from 25-35%. Symptoms and perceived indoor air quality were measured before and after the study period by a standardised self administered questionnaire. The technical measurements comprised room temperature, air humidity, static electricity, exhaust air flow, aerosols, microorganisms, and volatile organic compounds in the air. The most pronounced effect of the humidification was a significant decrease of the sensation of air dryness, static electricity, and airway symptoms. After four months of air humidification during the heating season, 24% reported a weekly sensation of dryness in humidified units, compared with 73% in controls. No significant changes in symptoms of SBS or perceived air quality over time were found in the control group. The room temperature in all units was between 21-23 degrees C, and no significant effect of air humidification on the air concentration of aerosols or volatile organic compounds was found. No growth of microorganisms was found in the supply air ducts, and no legionella bacteria were found in the supply water of the humidifier. Air humidification, however, significantly reduced the measured personal exposure to static electricity. It is concluded that air humidification during the heating season in colder climates can decrease symptoms of SBS and perception of dry air. PMID- 8000494 TI - Occupational hand dermatoses of hairdressers in Tainan City. AB - OBJECTIVES: To determine the prevalence, clinical features, and patterns of hand dermatosis in hairdressers in Tainan, Taiwan, and to examine the associations between patterns of dermatosis and risk factors such as job description, work exposure, and sensitisation to common allergens. METHODS: Interviews, examinations, and patch tests of the hairdressers from nine hairdressing stores randomly selected from Tainan City. Patch test agents included 41 substances with common allergens, shampoo preservatives, hair dyes, permanent waving and bleaching agents. RESULTS: 98 hairdressers finished the examination, 83% of them had occupational dermatosis and 32% had scissor induced scars or wounds. Most of the dermatoses belonged to either dry metacarpophalangeal dermatitis or eczema of the fingers. 44% of the hairdressers showed positive skin reaction to one or more patch test agents. The patch test results were different from previous reports in that the most common allergens were nickel, thimerosal, Captan, Kathon CG, and fragrance mix, and that the sensitivity to hair dye and permanent wave ingredients were low. The dry metacarpophalangeal dermatitis was associated with exposure to shampoo, and the eczema of the fingers with skin sensitivity to patch test agents. CONCLUSION: Hairdressers in Tainan City had a high prevalence of dermatoses including traumatic wounds, and allergic and irritant contact dermatitis. The rates of sensitivity to some of the common sensitising agents were different from previous reports. PMID- 8000496 TI - Evaluation of phosphine genotoxicity at occupational levels of exposure in New South Wales, Australia. AB - Phosphine has been claimed to cause chromosomal damage at exposures close to the current time weighted average exposure standard of 0.3 ppm (0.4 mg/m3). The current study involved 31 phosphine fumigators and 21 controls during the high fumigation season. All were volunteers and were evaluated for genotoxicity variables, including micronuclei in peripheral blood lymphocytes and urine mutagenicity. In parallel, all fumigators and 17 controls were evaluated for full haematology, multiple biochemical analysis, whole blood organochlorines, and whole blood and serum cholinesterase activity. The results for micronuclei showed no significant differences between fumigators and controls, but detected a strong association between age and increased frequency of micronuclei. Measurement of urine mutagenicity did not show any significant difference between fumigators and controls, but did show increased excretion of mutagens in smokers. All haematological and biochemical variables were within normal ranges, except for some non-specific changes in biochemistry. At monitored occupational exposures of < 2.4 ppm/h our results show no association between phosphine exposure and genotoxic or toxicological effects in fumigators. PMID- 8000495 TI - Time to pregnancy and occupational exposure to pesticides in fruit growers in The Netherlands. AB - OBJECTIVES: Although pesticides are regularly used in agriculture, relatively little is known about possible adverse health effects, especially reproductive effects, due to occupational exposure. This explorative study investigates the relation between exposure of the fruit grower to pesticides and fecundability (probability of pregnancy) in a population of fruit growers. METHODS: The analysis is based on self reported data and includes 91 pregnancies during 1978 1990 of 43 couples. Cox' proportional hazards model was used to analyse time to pregnancy after correction for gravidity and consultation with a physician for fertility problems. RESULTS AND CONCLUSIONS: Application of pesticides solely by the owner was associated with a long time to pregnancy, resulting in a fecundability ratio of 0.46 (95% confidence interval (95% CI) 0.28-0.77). Similarly a low spraying velocity (< or = 1.5 hectares/h) resulted in a fecundability ratio of 0.47 (95% CI 0.29-0.76) and is associated with the use of older spraying techniques and tractors without a cabin. These factors were assumed to cause high exposure, which was confirmed by exposure measurements in the field. The effect of high exposure was mainly apparent if the couple had intended to become pregnant in the period from March-November (fecundability ratio 0.42, 95% CI 0.20-0.92). This is the period in which pesticides are applied. Out of the spraying season the effect of a high exposure was absent (fecundability ratio 0.82, 95% CI 0.33-2.02). In the high exposure group 28% of the pregnancies had been preceded by consulting a physician because of fertility problems, compared with 8% in the low exposure group. These findings indicate that an adverse effect of exposure to pesticides on fecundability is likely. PMID- 8000497 TI - Upper airway irritation and small airways hyperreactivity due to exposure to potassium aluminium tetrafluoride flux: an extended case report. AB - OBJECTIVES: 22 workers, exposed to potassium aluminium tetrafluoride used as flux for soldering aluminium, were studied as clinical outpatients for symptoms of irritation of the nose, eye, skin, and airways. METHODS: 16 volunteered for spirometry with methacholine provocation test including a test for small airways function by volume of trapped gas (VTG). RESULTS: Median (range) latency time before respiratory symptoms developed was 6 (1-60) months. Symptoms of airways irritation diminished in all subjects after flux exposure ended. The FEV1 was within the normal range in 16 of 17 subjects before the methacholine provocation test. The FEV1 decreased by > or = 20% in two out of 16 subjects after the 0.1% methacholine provocation. Four out of the 17 subjects had a high VTG before methacholine provocation. After inhalation of 0.1% methacholine eight out of 16 subjects (50%) had an abnormal increase of VTG indicating hyperreactivity in small airways. DISCUSSION: Potassium aluminium tetrafluoride flux seems to induce an increase of bronchial reactivity in small airways. A setting of an occupational standard for potassium aluminium tetrafluoride is proposed. PMID- 8000498 TI - Occupational respiratory diseases in British Columbia, Canada in 1991. PMID- 8000499 TI - Death of a classified worker probably caused by overexposure to gamma radiation. AB - This paper describes the case of an industrial radiographer who was seriously overexposed to gamma radiation. The exact circumstances of this exposure were not established but it was concluded that he was repeatedly irradiated probably to a total average whole body dose of at least 10 Gy over several years. Also, a much larger dose to a hand required its partial amputation. He developed myelodysplasia, which progressed to acute myeloid leukaemia from which he died. Karyotypic examination of the leukaemic blasts showed changes very similar to those associated with secondary leukaemia that may develop after radio or chemotherapy. The paper describes his medical case history, the investigation of his workplace, and the attempts to estimate his radiation dose by chromosomal analysis of blood lymphocytes and electron spin resonance of dental enamel and bone. PMID- 8000500 TI - Study of occupational lung cancer in asbestos factories in China. PMID- 8000501 TI - Effects of carbamylcholine chloride on human antral gastrin mRNA levels. AB - The effects of the muscarinic receptor agonist, carbamylcholine chloride (carbachol), on gastrin release and gastrin mRNA levels in human antral mucosa (n = 15) were determined. During a-2-h incubation period, carbachol (10(-6)-10(-4) M) decreased gastrin mRNA levels to 71 +/- 8% (10(-6) M), 40 +/- 8% (10(-5) M), and 33 +/- 5% (10(-4) M) of control levels. Carbachol (10(-5) M) decreased intracellular gastrin (from 1634 +/- 103 to 1272 +/- 126 pg/mg tissue protein), while it increased gastrin release into the medium (from 609 +/- 48 to 918 +/- 68 pg/ml per mg tissue protein). After 6- and 9-h culture, carbachol gradually increased gastrin mRNA levels, by 96 +/- 12% and 126 +/- 23%, respectively. Atropine sulfate (10(-5) M) completely inhibited the carbachol-induced changes. Cycloheximide markedly decreased tissue gastrin concentration, but increased gastrin mRNA levels, whereas it had no effects on gastrin release. These findings suggested that carbachol may have a time-related biphasic action on human antral gastrin biosynthesis. PMID- 8000502 TI - Histogenesis of hyperplastic polyps of the stomach in terms of cellular proliferation. AB - We investigated the histogenesis of hyperplastic polyps of the stomach, in terms of cellular proliferation, by studying endoscopically removed and gastrectomized human gastric polyps either labeled with bromodeoxyuridine (BrdU) by in vitro flash labeling techniques or labeled in an isolated organ circulation system, in both of which, perfluorochemical artificial blood was employed. Immunohistochemistry with antibodies against BrdU and proliferating cell nuclear antigen (PCNA) was simultaneously employed. The generative cell zone of pedunculated and semipedunculated polyps was markedly expanded compared with that of the background mucosa, and this change also appeared in sessile polyps, although to a lesser degree. Enhanced proliferative activity was observed in both epithelial and stromal cells in areas of erosion. Our results demonstrate that the initial change in the histogenesis of hyperplastic polyps is an expansion of the generative cell zone, followed by interstitial edema and stromal cell proliferation, and that erosion can facilitate these changes. No correlation was found between the size of the polyps and the labeling indices. This finding explains, in part, the diversity of chronological changes in the size and shape of hyperplastic polyps. PMID- 8000503 TI - Biosynthesis and secretion of mucin-related products in Hs746T gastric cancer cells. AB - We have previously studied the biosynthesis and secretion of mucin in the normal human stomach and reported that the tetramer of the 60-kDa subunit of mucin core protein was synthesized and highly glycosylated, and that only high molecular weight mucin was secreted. In this study, we investigated the mucin-related products of a gastric cancer cell line (Hs746T). Analysis of intracellular and extracellular products immunoprecipitated with an anti-apomucin monoclonal antibody revealed that a 110-kDa protein, the dimer of the 55-kDa subunit, was synthesized and secreted. Tunicamycin treatment inhibited the secretion of the 110-kDa protein. These findings suggest that N-glycosylation may be involved in the secretory mechanism of the mucin-related product. PMID- 8000504 TI - Intestinal and extraintestinal complications of Crohn's disease: predictors and cumulative probability of complications. AB - Of 238 patients with Crohn's disease seen at our clinics from April 1973 to August 1988, 203 patients were selected for this study, since they fulfilled the following criteria: they had been followed up for more than 6 months as outpatients or had been treated as inpatients for more than 1 month. They were studied to elucidate: (a) the different types and incidence of various complications, (b) the factors related to complications present at the time of diagnosis, (c) predictors of new complications arising after diagnosis, and (d) the cumulative incidence of complications occurring during the course of the disease from the times of onset and diagnosis. Of the intestinal complications, perianal fistula was most common (33%), followed by strictures with dilatations of the proximal bowel (21%), and internal fistula (14%). Of the extraintestinal complications, menstrual disturbance was the most common (18% of the female patients), followed by arthritis (10%), and aphthous stomatitis (10%). As for the factors influencing complications present at the time of diagnosis, the pattern of bowel involvement was significantly correlated with the presence of intestinal stricture, while the erythrocyte sedimentation rate was significantly correlated with the presence of perianal fistula. A significant predictor of new complications arising after diagnosis was the general well-being of patients at the time of diagnosis. Patients who, at diagnosis, already have complications such as stricture, abdominal abscess, internal or external fistula, massive hemorrhage, and free perforation or anal lesions are more likely to develop new complications in addition to those present at diagnosis, compared with patients without any complications at diagnosis (P = 0.055). PMID- 8000505 TI - Prevalence of HCV genotype among patients with chronic liver diseases in the Tokyo metropolitan area. AB - We examined 613 Toranomon Hospital patients with HCV RNA-positive chronic liver disease to elucidate the viral genotype in the Tokyo metropolitan area. An epidemiological and clinical study was conducted in the 565 patients whose HCV genotype could be determined. The HCV genotypes found were type II, in 414 patients (67.5%); type III, in 103 (16.8%); type IV, in 37 (6.0%); type V, in 4 (0.7%); mixed genotype II and III, in 5 (0.8%); and mixed genotype II and IV, in 2 (0.3%). The HCV genotype could not be determined in 48 patients. Type II was most prevalent. The HCV genotype I was not found at all. There were no significant differences between genotypes in relation to sex, age, history of blood transfusion, or the progression of the disease. It was uncommon to find a history of blood transfusion in the patients with mixed genotypes; however, a high incidence of hepatic disorders was noted among the family members of these patients. Ninety-two percent of the patients with HCV genotype II tested positive for C100-3, while 70.9% of those with type III, and 43.2% of those with type IV tested positive for this antibody. HCV genotype II was most prevalent, and the positivity rate for anti C100-3 in patients with this HCV genotype was significantly higher (P < 0.00001) than that in patients with the other genotypes. PMID- 8000506 TI - Dynamic aspects of glutathione metabolism in obstructive jaundice. AB - The dynamic aspects of glutathione metabolism during obstructive jaundice were analyzed in rats. Plasma bilirubin levels increased after ligation of the bile duct, with a concomitant increase in hepatorenal glutathione levels. When the bile duct was recanalized, plasma bilirubin levels rapidly decreased, with a concomitant decrease in hepatorenal glutathione levels. The half-life of hepatic glutathione turnover increased markedly after bile duct obstruction, returning to normal after recanalization of the bile duct. Intravenous administration of a loading dose of bilirubin inhibited the biliary secretion of glutathione in a dose-dependent manner. On the other hand, renal glutathione efflux increased markedly after bile duct obstruction. These observations suggest that glutathione status is significantly affected in obstructive jaundice, predominantly due to the inhibition of hepatic secretion by increased bilirubin. PMID- 8000507 TI - Correlation between serum levels of alanine aminotransferase and ferritin in male blood donors with antibody to hepatitis C virus. AB - Chronic hepatitis C has been demonstrated to be associated with hepatic iron overload, and the hypothesis that the disease activity of hepatitis C is associated with iron cytotoxicity was tested in male volunteer blood donors. Sera with either antibody to hepatitis C virus or hepatitis B surface antigen were selected for determination of ferritin concentration and alanine aminotransferase activity. A correlation between serum ferritin concentration (Y; microgram/l) and alanine aminotransferase activity (X; IU/l) was found in donors with antibody to hepatitis C (log Y = 0.65 x log X + 0.98, r = 0.53, and P < 0.01). The correlation was lower in donors with hepatitis B surface antigen (r = 0.37; P < 0.01). Hepatitis C virus infection probably induces time-dependent iron accumulation associated with the progression of disease activity, while hepatitis B virus infection results in a variety of iron loads with different clinical features. The high disease activity related to hyperferritinemia suggests the presence of iron-induced liver damage in donors with hepatitis C. PMID- 8000508 TI - Ethanol inhibits asialoglycoprotein receptor synthesis but augments its mRNA expression in a human hepatoma cell line. AB - The effect of ethanol on the expression of asialoglycoprotein receptor protein and its mRNA was studied in a human hepatoma cell line, HepG2. The number of asialoglycoprotein receptors on the cell surface was decreased to 60% of the control level, without a loss in affinity, by incubating the cells with 100 mM ethanol. The decrease in cell surface asialoglycoprotein receptors was paralleled by a decrease in total receptor numbers, including intracellular and surface receptors. The internalization of asialoglycoprotein was also diminished, to 44% of that in control cells. The decreases in cell surface receptors and total receptor numbers were partially restored by 2 mM 4-methylpyrazole, suggesting that ethanol metabolites participated in the diminution of asialoglycoprotein receptor expression. However, the steady-state expression of asialoglycoprotein receptor mRNA was increased in ethanol-treated cells and further augmented by a longer ethanol exposure. These paradoxical results, i.e., the decrease of asialoglycoprotein receptor protein and the increase of its mRNA expression, suggest that the reduction in the asialoglycoprotein receptor protein is a post transcriptional event and that a possible feedback regulatory mechanism may control asialoglycoprotein receptor gene transcription and/or impair the degradation of its mRNA. PMID- 8000509 TI - Osteopenia in primary biliary cirrhosis and cirrhosis of the liver in women, evaluated by dual-energy X-ray absorptiometry. AB - To study bone involvement in primary biliary cirrhosis (PBC), we used dual-energy X-ray absorptiometry to measure bone mineral density (BMD) in Japanese women with PBC and with cirrhosis of the liver. In both groups, in each decade up to 60 years of age, the mean BMD of the lumbar spine was not significantly different from that in healthy Japanese women; however, in patients aged 60 years or more, the level was significantly lower both in the patients with PBC (P < 0.001) and in those with cirrhosis of the liver (P < 0.01). Patients with PBC were also examined by single-photon absorptiometry. The BMD of the radius in the patients with PBC was less changed than that of the lumbar vertebrae; thus, the bone changes in PBC seem to be greater in spongy than in cortical bone. PMID- 8000510 TI - Serum trace metals in chronic viral hepatitis and hepatocellular carcinoma in Thailand. AB - This study was conducted to determine and compare serum trace metal levels in viral hepatitis-associated chronic liver disease. Of 98 patients aged 43 (+/- 13) [mean (+/- SD)] years, 83 (85%) were seropositive for hepatitis B surface antigen (HBsAg) and 15 (15%) were seropositive for anti-hepatitis C virus (HCV). Twenty five patients had chronic persistent hepatitis, 32 chronic active hepatitis, 21 post-necrotic cirrhosis, and 20 hepatocellular carcinoma. Determination of fasting serum trace metal levels (zinc, copper, calcium, magnesium, and phosphorus) was performed after the patients had been on a 2-day diet containing 10-12 mg zinc/day. Compared to healthy volunteers (n = 30), serum zinc levels were significantly decreased in patients with chronic active hepatitis, cirrhosis, and hepatocellular carcinoma (P < or = 0.0001), and copper levels were significantly elevated only in patients with hepatocellular carcinoma (P < 0.0001). The overall serum levels of calcium, magnesium, and phosphorus were within normal ranges, and levels of calcium and magnesium correlated with serum zinc (P = 0.01-0.03). Serum zinc levels correlated with bilirubin, albumin, and cholesterol (P = 0.0004 < or = 0.0001), but not with daily urinary zinc excretion. Serum copper levels correlated with alkaline phosphatase and gamma glutamyltransferase (P = 0.008-0.0001). These results suggested that changes in liver cell pathology compounded by functional impairment may alter the metabolism of trace metals, in particular, zinc and copper. The possible relationship of these changes to the pathogenesis of chronic liver disease is discussed. PMID- 8000512 TI - Small duct cholangitis induced by N-formyl L-methionine L-leucine L-tyrosine in rats. AB - Primary sclerosing cholangitis (PSC) frequently accompanies inflammatory bowel diseases. In an attempt to increase our understanding of the pathogenesis of PSC, we studied bile duct changes in rats with colitis which had been given N-formyl L methionine L-leucine L-tyrosine (fMLT) rectally; fMLT is one of the chemotactic peptides produced by Escherichia coli, and is secreted into the bile by hepatocytes after it enters the portal blood. Transrectal administration of fMLT induced a marked inflammation in the portal triad and mild hepatocyte necrosis on the 4th day. The infiltrating leukocytes in the portal tract were mostly mononuclear cells, which densely infiltrated around the bile ducts. These mononuclear cells appeared to attach to bile duct epithelial cells, and they were more numerous in the smaller bile ducts. Electron microscopy revealed that lymphocytes were in direct contact with bile duct lining cells and that some epithelial cells had degenerated or collapsed. These results suggest that this E. coli-derived peptide may induce cholangitis in the small bile duct through cell mediated mechanisms. Since these pathologic changes resemble those of the bile duct observed in the early stage of PSC, it can be concluded that bacterial chemotactic peptides may play a role in the pathogenesis of small-duct PSC. PMID- 8000511 TI - Identification and characterization of dehydrocholic acid reductase system in the cytosol of human red blood cells. AB - We conducted in vivo and in vitro studies of the reductive metabolism of the cholagogue, dehydrocholic acid (DHCA). Immediately after the intravenous administration of 1 g of DHCA in normal subjects (n = 6), the concentration of the reductive metabolite, 3 alpha-hydroxy-7,12-dioxo-cholanoic acid (unconjugated form), increased sharply in the systemic circulation, rising to 95.8 microM 10 min after administration. The results of in vitro experiments with DHCA and whole blood showed that 3 alpha-hydroxy-7,12-dioxocholanoic acid were produced from DHCA. In vitro experiments using DHCA and the red blood cell fraction, and DHCA and the red blood cell cytoplasmic fraction gave similar results to those described above with whole blood. However, a reductive metabolite was not formed by the incubation of DHCA and the red blood cell membrane fraction. These findings indicated that, contrary to the conventional theory that intravenously administered DHCA is subjected to reductive metabolism only in the liver, reduction also occurs in the systemic circulation, and the mechanism for this reductive metabolism is present in the cytoplasmic fraction of red blood cells. Further investigation to characterize this reductive metabolic system revealed an optimum temperature of 37 degrees C, an optimum pH of 7.4, a Km value of 2.0 x 10(-3) M, and inactivation by heat treatment (70 degrees C for 2 min). PMID- 8000513 TI - A rare case of achalasia coexistent with sigmoid megacolon and associated with epilepsy. AB - A case of achalasia coexistent with sigmoid megacolon in a 38-year-old man with known epilepsy is described. The patient was referred to the Ryukyu University Hospital with a 4-year history of dysphagia and heartburn and a 1-year history of abnormal bowel movement. On admission, upper gastrointestinal (GI) series demonstrated a dilated, tortuous thoracic esophagus with a flask-type configuration. Barium enema studies showed a dilated sigmoid colon from the rectosigmoid junction to the descending colon. Myotomy (modified Jekler-Lhotka's procedure) for achalasia and simple sigmoidectomy for sigmoid megacolon were carried out. The biopsied wall of the narrowed esophageal segment at operation showed decreased numbers of ganglion cells in Auerbach's plexus and atrophy of the muscle fibers. The resected dilated sigmoid colon revealed degeneration and markedly decreased numbers of ganglion cells in Auerbach's and Meissner's plexuses. The patient's postoperative course was uneventful and he has been doing well since surgery. The present case is very interesting and to our knowledge, such a case is rare in the literature. We believe that the abnormalities of the ganglion cells may be due to the same etiologic factor as the sigmoid megacolon. The association of the two pathologic processes is discussed, together with a brief review of the literature. PMID- 8000514 TI - A case of primary gastric choriocarcinoma and a review of the Japanese literature. AB - A 63-year old woman who had experienced melena for 2 weeks was admitted to Tokyo University Hospital. Gastric adenocarcinoma was diagnosed endoscopically and histologically, and a total gastrectomy was performed soon thereafter. Pathological examination of the resected stomach revealed choriocarcinoma of the stomach. Although chemotherapy was administered after surgery, she died 3 months after admission. Autopsy confirmed the diagnosis of primary gastric choriocarcinoma, a rare, but highly malignant tumor. It is characteristic; macroscopically it forms a necrotic mass with bleeding, and microscopically it often consists of adenocarcinoma and choriocarcinoma. Since its prognosis is extremely poor, we must take into account the possibility of primary gastric choriocarcinoma when a hemorrhagic gastric tumor with necrosis is found. PMID- 8000515 TI - Carcinoma of the colon in children: case report and review of the Japanese literature. AB - A 15-year-old female presenting with anemia and positive for occult blood was diagnosed as having an adenomatous polyp with mild atypia in the cecum by colonoscopy. Microscopically, the majority of the surface of the tubulovillous adenoma was occupied by a well-differentiated adenocarcinoma, indicating that the adenoma-carcinoma sequence is involved in the development of colon cancers, even in children. Forty-three cases of proven carcinoma of the colon in Japanese children aged under 15 years are also reviewed. The majority of the patients were aged over 10. Although an emergency laparotomy was undertaken in 42.5% of these patients, the signs and symptoms observed in these children did not markedly differ from those of adults. Colon cancer should not be excluded in children only on the basis of age, and barium enema and colonoscopy should therefore be applied to pediatric patients with unexplainable bleeding and abdominal pain, especially those over 10 years of age. PMID- 8000516 TI - Fulminant hepatitis following bone marrow transplantation in hepatitis B virus carrier siblings. AB - A 19-year-old male healthy hepatitis B virus (HBV) carrier developed fulminant hepatitis following allogenic bone marrow transplantation (BMT) from his brother, who was also a healthy HBV carrier, during the first complete remission of acute myelogenic leukemia (M1, FAB classification). Serum markers related to both HBV and hepatitis C virus (HCV) were elevated during active liver injury when a point mutation in the precore (pre-C) region occurred in the HBV. The patient received low-dose interferon alpha (IFN-alpha), while the dose of cyclosporin A was tapered; the patient eventually recovered from the liver injury. Fulminant hepatitis due to HBV and/or HCV following BMT is rare, and it is considered to have a very poor prognosis. The rationale for the use of low-dose IFN-alpha with cyclosporin A (CyA) is discussed. PMID- 8000517 TI - Aberrant hepatic duct connected with the main pancreatic duct by anomalous pancreato-biliary ductal union: case report. AB - An aberrant hepatic duct directly connected to the main pancreatic duct with anomalous arrangement of the pancreato-biliary ductal system is reported here, the first report of such a case, to our knowledge. A 53-year-old woman was admitted to our hospital because of cholecystolithiasis with abdominal pain in the right upper quadrant. Endoscopic retrograde cholangiopancreatography (ERCP) showed that an aberrant hepatic duct, which independently drained the right posterior segment of the liver, connected to the main pancreatic duct at a high insertion site distal to the sphincter area of the major papilla. The common bile duct (containing stones), on the other hand, united with the main pancreatic duct in a normal fashion. Cholecystectomy and bile duct lithotomy were performed. The aberrant hepatic duct was separated from the main pancreatic duct just above the junction, and was anastomosed side-by-side to the common hepatic duct. The embryologic development of this lesion is not clear, but is discussed in this report. PMID- 8000518 TI - Choledochocele with obstructive jaundice: a case report and a review of the Japanese literature. AB - A case of a 57-year-old farmer with a rare type of choledochal cyst (choledochocele; Alonso-Lej's type III) is described. The patient was admitted because of obstructive jaundice and acute biliary infection. Abdominal computed tomography scan showed a cystic lesion in the head of the pancreas, and endoscopic retrograde cholangiopancreatography disclosed cystic dilatation of the terminal portion of the common bile duct. It was suspected that the choledochocele could swell and compress the common bile duct, causing obstructive jaundice and acute cholangitis; therefore, it was surgically resected. We also reviewed 61 cases of choledochocele reported in Japan; the findings were similar to those reported in the English literature. PMID- 8000519 TI - Cholangiographic appearance of multiseptate gallbladder: case report and a review of the literature. AB - A case of multiseptate gallbladder is described, with a review of the literature. This is the 24th such case report. The patient complained of right upper quadrant pain, colicky in nature. Abdominal ultrasonography showed multiple fine echoes within the gallbladder. On endoscopic retrograde cholangiography, multiple radiolucent lines crossing the gallbladder in various directions were noted within the gallbladder. The gallbladder was crisscrossed by numerous delicate septations and had a honeycomb appearance. These findings suggested multiseptate gallbladder. PMID- 8000520 TI - A case of choledochal cyst associated with adenocarcinoma exhibiting sarcomatous features. AB - One complication of choledochal cyst in adulthood is the development of secondary carcinoma, usually well-differentiated adenocarcinoma. We report a case of extrahepatic bile duct carcinoma associated with choledochal cyst and presenting predominantly sarcomatous features. The patient was a 52-year-old female who presented with abdominal fullness and pain. Ultrasound (US), computed tomography (CT), and cholangiography revealed a choledochal cyst with a tumor. The resected choledochal cyst was 10 x 7.5 cm and contained a protruding, ulcerated tumor, measuring about 4.0 x 2.5 cm. Histologically, the tumor was composed of spindle shaped or fusiform cells with occasional pleomorphic or bizarre giant cells and abundant fibrous stroma, similar to malignant mesenchymal tumors. However, further histologic and immunohistochemical examination revealed that the tumor was adenocarcinoma with prominent sarcomatous features. To our knowledge, sarcomatous change in extrahepatic bile duct carcinoma associated with choledochal cyst has not been previously described. PMID- 8000521 TI - Forty-two patients with acute ascaris pancreatitis in China. AB - Acute pancreatitis caused by Ascaris lumbricoides is more common in certain areas than is generally appreciated. We report a series of 42 patients, mostly young adult women, admitted to our hospital in Hunan Province, China, during the period January, 1983 to December, 1992. The diagnosis was based on the detection of worms by ultrasonography, and on the presence of severe upper abdominal pain and tenderness and raised serum amylase level without other apparent causes. Only 2 patients had necrotizing pancreatitis (4.8%). With our conservative policy, 40 patients recovered and 2 patients were operated. The mortality has remained at zero and we therefore believe that early surgical intervention is unwise. However, laparotomy should be performed if the patient fails to respond to conservative therapy, there is evidence of infection around the pancreas, bloody peritoneal fluid on aspiration, and dead worms remain within the biliary tree. We compare acute ascaris pancreatitis with acute pancreatitis caused by lithiasis. PMID- 8000522 TI - Four cases of acute liver damage following the ingestion of a sea hare egg. PMID- 8000523 TI - Induction of a 72-kDa heat shock protein in rat colonic mucosa by oral lavage solution. PMID- 8000524 TI - Preservation records of micro-organisms: evidence of the tenacity of life. PMID- 8000525 TI - Two genetically-distinct and differentially-regulated aconitases (AcnA and AcnB) in Escherichia coli. AB - An acnA mutant of Escherichia coli was constructed by replacing the chromosomal acnA gene by an internally deleted derivative containing a kanR cassette. Southern and Western blotting confirmed that the acnA gene had been replaced by the disrupted gene and that the aconitase A protein was no longer expressed. However, the mutant failed to exhibit the anticipated glutamate auxotrophy and it retained a residual aconitase activity. This activity was due to an analogous unstable enzyme(s) designated aconitase B. Studies on the regulation of aconitase A synthesis using an acnA-lacZ translational fusion showed that the acnA gene resembles other citric acid cycle genes in being subject to CRP-mediated catabolite repression and ArcA-mediated anaerobic repression. In addition to being activated by the SoxRS oxidative stress regulatory system, the acnA gene appeared to be activated by the ferric uptake regulator (Fur). It was concluded that the acnA gene belongs to at least four global regulatory networks, crp, arcA, fur and soxRS. In contrast, the aconitase B activity decreased after exposure to oxidative stress and was less affected by anaerobiosis. Comparable studies with the fumarase genes (fumA, B and C) indicated that fumA (encoding the unstable aerobic iron-sulphur-containing fumarase) is activated by the ferric uptake regulator (Fur) and fumC (encoding the stable fumarase) is activated by the SoxRS oxidative stress regulatory system. PMID- 8000526 TI - Isolation of the Thiobacillus ferrooxidans ntrBC genes using a T. ferrooxidans nifH-lacZ fusion. AB - An agar plating technique was developed in which the activation of expression of a Thiobacillus ferrooxidans nifH-lacZ gene fusion was used to isolate the ntrBC genes from a T. ferrooxidans gene library. An Escherichia coli ntrC mutant containing the nifH-lacZ fusion was transformed and plated on a low-nitrogen medium so that on flooding with ONPG, the production of yellow colonies indicated the presence of the cloned T. ferrooxidans ntrBC genes. A 4.47 kb region from the T. ferrooxidans chromosome was sequenced. Analysis of the sequence revealed that the ntrB and ntrC genes were closely linked to a third ORF of unknown function. Analysis of the 900 bp region upstream of the T. ferrooxidans ntrBC genes and Southern hybridization experiments confirmed that in T. ferrooxidans ATCC 33020, the glnA and ntrBC genes are unlinked. Expression of the T. ferrooxidans nifH lacZ fusion in E. coli was activated in the presence of the T. ferrooxidans ntrBC genes and regulated by nitrogen. PMID- 8000527 TI - Possible function and some properties of the CcpA protein of Bacillus subtilis. AB - The ccpA mutations alsA1 (alsA1 is allelic to ccpA) and ccpA::Tn917 completely abolished catabolite repression of gluconate kinase and sorbitol dehydrogenase synthesis in Bacillus subtilis, whereas they only partially affected the catabolite repression of inositol dehydrogenase, histidase and xylose isomerase synthesis. The alsA1 mutation also partially affected catabolite repression of sporulation. Analysis of revertants from the alsA1 mutant by direct sequencing indicated that this mutation comprises a base substitution of guanine at nucleotide -14 to adenine within the Shine-Dalgarno sequence of the ccpA gene (ccpA translation starts at nucleotide +1). A 1.37 kb EcoRI fragment carrying the ccpA gene was cloned into Escherichia coli plasmid pUC19 and B. subtilis plasmid pUB110, resulting in plasmids pCCPA19 and pCCPA110, respectively. The ccpA gene carried in pCCPA110 complemented the alsA1 mutation. Western blotting revealed that the level of the CcpA protein in B. subtilis cells, which seemed to be constitutively synthesized, was approximately 10 times lower for the alsA1 mutant than for the wild-type. The CcpA protein synthesized by either E. coli cells bearing pCCPA19 or B. subtilis cells bearing pCCPA110 was purified to over 90% homogeneity; the latter cells were grown in the presence of glucose. The molecular mass of the protein purified from E. coli was 74 kDa, suggesting that this protein exists as a dimer because its subunit molecular mass was 38 kDa as determined by SDS-PAGE. Gel retardation analysis indicated that the purified CcpA protein in both cases did not bind to the cis sequence for catabolite repression of the gnt operon, but it bound non-specifically to DNA. PMID- 8000528 TI - An investigation of plasmids from Staphylococcus aureus that mediate resistance to mupirocin and tetracycline. AB - Plasmids conferring mupirocin resistance were prepared from isolates of Staphylococcus aureus obtained from four patients in the same ward. The plasmids are related and in all of them the gene conferring mupirocin resistance (mupA) is flanked by copies of IS257 in direct repeat. In two plasmids mupA and IS257 have been duplicated and in one of these plasmids (pJ3358) a small pT181-like plasmid conferring tetracycline resistance is present flanked by copies of IS257. Filter mating with a strain containing pJ3358 as donor and selection on tetracycline sometimes resulted in transfer of the pT181-like plasmid containing a copy of IS257. Analysis showed that the pT181-like plasmid with the insertion of IS257 is present in high copy number and that the IS257 element is inserted in the copy number control region of the plasmid. PMID- 8000529 TI - A Lactococcus lactis gene encodes a membrane protein with putative ATPase activity that is homologous to the essential Escherichia coli ftsH gene product. AB - A gene, encoding a protein homologous to an essential Escherichia coli protein, FtsH, was identified adjacent to the hpt gene and the trnA operon in the Gram positive bacterium Lactococcus lactis. The deduced amino acid sequence of the gene product showed full-length similarity to FtsH of E. coli, Yme1p of Saccharomyces cerevisiae and a conserved region found in a new family of putative ATPases. In-frame fusions of L. lactis ftsH and phoA1 in E. coli, and immunodetection of the L. lactis FtsH protein in cell fractions using anti-E. coli FtsH serum showed that L. lactis ftsH was expressed and encodes a membrane protein. When contained on a high copy number plasmid, the L. lactis ftsH gene complemented the lethality of a delta ftsH3::kan mutation in E. coli at 37 degrees C and below, indicating that the L. lactis ftsH gene can functionally replace the E. coli ftsH gene to some extent. The resulting E. coli strain showed temperature sensitivity and salt sensitivity. A L. lactis mutant with an insertion into ftsH was salt-, heat- and cold-sensitive. These results suggest that FtsH is somehow involved in stress responses. Southern hybridization analysis indicated that genes homologous to ftsH of L. lactis were also present in Bacillus subtilis, and several Lactobacillus and Leuconostoc species, suggesting high conservation of ftsH in bacterial species. PMID- 8000530 TI - Regulation of the gene encoding translation elongation factor 3 during growth and morphogenesis in Candida albicans. AB - The level of the TEF3 mRNA, which encodes the fungal-specific translation elongation factor 3 (EF-3), was measured during the yeast-to-hyphal transition in Candida albicans. In contrast to a previous report, TEF3 mRNA levels were shown to change during dilution into fresh medium, increasing only transiently when dimorphism was induced by either (i) an increase in growth temperature (from 25 degrees C to 37 degrees C) combined with the addition of 10% (v/v) bovine calf serum to the medium, or (ii) an increase in growth temperature (from 25 degrees C to 37 degrees C) combined with an increase in the pH of the medium (from pH 4.5 to 6.5). TEF3 mRNA levels also increased in control cultures under conditions where germ tubes were not formed, but they remained elevated in contrast to cultures undergoing morphological changes. TEF3 mRNA levels were not significantly affected by heat-shock, but were tightly regulated during batch growth of the yeast form, reaching maximal levels in exponential phase. Therefore, the changes in TEF3 expression that accompany the dimorphic transition in C. albicans appear to reflect the underlying physiological changes that occur during morphogenesis and are not a response to morphogenesis per se. For this reason TEF3 mRNA measurement cannot be used as a loading control in Northern analyses of dimorphic gene regulation. Comparison of TEF3 mRNA levels with the abundance of the EF-3 polypeptide indicated that the synthesis of this essential translation factor might be subject to post-transcriptional regulation. PMID- 8000531 TI - Glucose-transport-deficient mutants of Schizosaccharomyces pombe: phenotype, genetics and use for genetic complementation. AB - Glucose-transport-deficient mutants of Schizosaccharomyces pombe were obtained by treatment of wild-type cells (972h-) with N-methyl-N'-nitro-N- nitrosoguanidine, and by selection of resulting mutants on gluconate medium containing 0.05% 2 deoxy-D-glucose (2DG). One mutant, designated YGS-B22, was unable to grow on D glucose and/or D-fructose as a carbon source (Glc/Fru-), and was resistant to 2DG; hence, none of the three sugars was taken up by the mutant cells. The hexokinase activity in the wild-type and the mutant cells was equal. Genetic purification of YGS-B22 by back-crossing with a leucine-auxotrophic mutant and the wild-type resulted in two strains: YGS-4, with reduced 2DG resistance, and YGS-5, which had lost 2DG-resistance. YGS-5 grew in D-glucose-containing media, albeit very slowly. No measurable sugar uptake was detectable in either of the two mutants within the 1 h test interval. Tetrad analyses proved a Mendelian segregation of growth on D-glucose and leucine auxotrophy. However, 2DG resistance did not co-segregate with the Glc/Fru- phenotype, indicating that the transport deficiency and 2DG resistance characters are not encoded on the same genomic locus. Using a genomic bank of Sch. pombe, two transformants, YGS-5-G7 and YGS-5-G12, were found which had regained the wild-type growth and transport phenotype by complementation. Correspondingly, both D-glucose uptake and 2DG accumulation were restored in the transformed strains.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8000532 TI - Concomitant appearance of intrinsic thermotolerance and storage of trehalose in Saccharomyces cerevisiae during early respiratory phase of batch-culture is CIF1 dependent. AB - Strains of Saccharomyces cerevisiae that exhibit varied capacities for accumulation of trehalose were tested for intrinsic thermotolerance. Yeast that accumulated trehalose rapidly in early respiratory phase showed equally rapid attainment of thermotolerance, whereas a strain unable to accumulate trehalose at this stage of culture showed markedly delayed appearance of thermotolerance. These results were obtained using closely related but non-isogenic diploids and so it is possible that variable factors other than trehalose were responsible for the observed thermotolerance effects. Therefore, a pair of isogenic diploid S. cerevisiae strains was generated to facilitate further testing of whether trehalose functions in intrinsic stress tolerance. Both isogenic strains inherited a partially reverted cif1 phenotype, designated CPR, from the trehalose deficient progenitor that had been used in construction of the non-isogenic strains. The CPR phenotype permitted growth on glucose but not accumulation of trehalose, indicating that not all cif1-related deficiencies were suppressed in the CPR strains. However, one of the isogenic CPR pair was cif1/cif1 and failed to accumulate trehalose, whilst the other was cif1/CIF1 and was able to accumulate this sugar. The trehalose-proficient strain showed intrinsic stress tolerance whereas the trehalose-deficient strain was sensitive to heat stress during early respiratory growth. These results suggest that one or more functions of CIF1, not operating in the cif1/cif1(CPR) strains, are important for intrinsic thermotolerance of yeast in early respiratory phase.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8000533 TI - Nitrite causes reversible inactivation of nitrate reductase in the yeast Hansenula anomala. AB - The addition of nitrite, the product of the reaction catalysed by nitrate reductase, to cell suspensions of the yeast Hansenula anomala caused a reversible inactivation of NADPH-dependent nitrate reductase activity. The haem- and Mo dependent and Mo-dependent activities of nitrate reductase, determined with the non-physiological electron donors FMNH2 and reduced methyl viologen respectively, were less affected. A similar inactivation was found with the proton ionophores 2,4-dinitrophenol and carbonyl cyanide m-chlorophenylhydrazone. The inactive enzyme was found in the particulate fraction and cosedimented with the mitochondrial fraction. When the NADPH-dependent nitrate reductase activity was restored in vivo the enzyme was found in the soluble fraction. The inactivation of nitrate reductase by nitrite, 2,4-dinitrophenol and carbonyl cyanide m chlorophenylhydrazone was dependent on the external pH. The treatment of isolated mitochondria at alkaline pH with Triton X-100 solubilized about 30% of the inactive enzyme. PMID- 8000534 TI - Vesicles prepared from Streptococcus mutans demonstrate the presence of a second glucose transport system. AB - Streptococcus mutans, an important aetiological agent of dental caries, is known to transport glucose via the phosphoenolpyruvate (PEP) phosphotransferase system (PTS). An alternative non-PTS glucose transport system in S. mutans Ingbritt was suggested by the increased ATP-dependent phosphorylation of glucose and the presence of higher cellular concentrations of free glucose in cells grown in continuous culture under PTS-repressed conditions compared to those resulting in optimal PTS activity. A method was developed for the preparation of membrane vesicles in order to study this system in the absence of PTS activity. These vesicles had very low activity of the cytoplasmic enzymes, glucokinase, pyruvate kinase and lactate dehydrogenase. This, coupled with the lack of glycolytic activity and the inability to transport glucose, suggested that the vesicles would also be deficient in PTS activity because of the absence of the general soluble PTS proteins, Enzyme I and HPr, required for the transport of all PTS sugars. Freeze-fracture electron microscopy and membrane H(+)-ATPase analysis indicated that over 90% of the vesicles had a right-side-out orientation. Vesicles from cells grown in continuous culture under PTS-dominant and PTS repressed conditions both exhibited glucose counterflow. This indicates the presence of a constitutive non-PTS carrier in the organism capable of transporting glucose and utilizing ATP for glucose phosphorylation. Analysis of growth yields of cells grown under PTS-repressed and PTS-optimal conditions suggests that ATP, or an equivalent high energy molecule, must be involved in the actual transport process. This analysis is consistent with an ATP-binding protein model such as the Msm transport system reported by R. R. B. Russell and coworkers (J Biol Chem 267, 4631-4637), but it does not exclude the possibility of a separate permease for glucose. PMID- 8000535 TI - Characteristics of Helicobacter pylori growth in a defined medium and determination of its amino acid requirements. AB - A defined medium has been developed for Helicobacter pylori that gives growth characteristics (growth rate, maximum cell number and maximum colony-forming-unit count) comparable to those in a complex medium (Isosensitest broth + 5%, v/v, foetal bovine serum). Differences found in the death rate reflected a partial (50%) conversion to a coccoid cell form of the organism in the stationary and death phase in the defined medium, versus the almost complete (> 99%) conversion seen in the complex medium. The medium was used to study the amino acids required for growth by 10 strains of H. pylori. All strains required arginine, histidine, isoleucine, leucine, methionine, phenylalanine and valine, and eight of the strains also required alanine; five of the strains required serine. In the absence of glucose none of the 20 amino acids tested elicited growth when added at high concentration. However, in the presence of glucose, alanine induced considerably enhanced growth over that seen in the control, consistent with its use either as a nitrogen source or possibly an additional carbon source. The medium described will facilitate investigations into the metabolism and physiology of H. pylori, previously only possible with sophisticated approaches such as nuclear magnetic resonance spectroscopy. PMID- 8000536 TI - The utilization of thiocyanate as a nitrogen source by a heterotrophic bacterium: the degradative pathway involves formation of ammonia and tetrathionate. AB - A Gram-negative soil bacterium (isolate 26B) has been shown to utilize up to 100 mM thiocyanate as a source of nitrogen when supplied with glucose as the source of carbon and energy. During growth of isolate 26B with thiocyanate as the source of nitrogen, no ammonia, nitrate, nitrite, cyanide, cyanate, sulfate, sulfite, sulfide or carbonyl sulfide was detected in the growth medium. Growth of the bacterium on 14C-labelled thiocyanate (1.6 microCi) and glucose, yielded 14C labelled carbon dioxide (0.9 microCi). The addition of 2.9 mM thiocyanate to a bacterial suspension in phosphate buffer (50 mM, pH 7.4) resulted in the utilization of 2.1 mM thiocyanate and the production of 2.0 mM ammonia. This activity was inducible and only occurred after growth of the bacterium with thiocyanate as the source of nitrogen. Tetrathionate (0.7 mM) was detected in the medium after the utilization of thiocyanate (2.4 mM) by a suspension of the bacterium in phosphate buffer, and thiosulfate (1.0 mM) was detected as an intermediate. The addition of sulfide or thiosulfate to the bacterial suspension also resulted in the formation of tetrathionate. The utilization of both of these compounds appeared to be constitutive. A pathway for thiocyanate utilization by isolate 26B is proposed which involves the hydrolysis of thiocyanate to produce cyanate and sulfide. The cyanate then undergoes further hydrolysis to form ammonia and carbon dioxide. The sulfide is ultimately oxidized to tetrathionate via a pathway which includes thiosulfate. PMID- 8000537 TI - Chemical characterization of lipopolysaccharides from Legionella feeleii, Legionella hackeliae and Legionella jordanis. AB - Lipopolysaccharides (LPS) from Legionella feeleii serogroup 1, L. hackeliae serogroup 1 and L. jordanis were subjected to chemical analysis. All three LPS contained D-mannose, D-glucose, D-glucosamine, L-glycero-D-manno-heptose, 2-keto 3-deoxyoctonic acid and glycerol. In addition the LPS of L. feeleii was characterized by L-quinovose (tentatively identified) and L-fucosamine, L. hackeliae LPS by D-quinovosamine, D-galactosamine and D-galacturonic acid, and L. jordanis LPS by D-quinovosamine. Phosphorylated sugars were detected in all three LPS. The backbone sugar of the lipid A part was in each case 2,3-diamino-2,3 dideoxy-D-glucose substituted with a complex pattern of fatty acid, including 20 22 different amide-linked (non-branched and methyl-branched) 3-hydroxy fatty acids of chain-length ranging from 12 to 23 carbon atoms. The fatty acid patterns included also ester-linked nonhydroxylated entities and the uncommon 27-oxo octacosanoic acid and 29-oxotriacontanoic acid. The LPS of L. hackeliae and L. jordanis also contained heptacosane-1,27-dioic and nonacosane-1,29-dioic acid, and their 2-hydroxy analogues were characteristic of L. jordanis LPS. SDS-PAGE patterns of the three LPS were distinctly different. Both L. feeleii and L. jordanis produced smooth-form LPS with characteristic ladder patterns, whereas L. hackeliae LPS were of more rough-type character. PMID- 8000538 TI - Arabinase gene expression in Aspergillus niger: indications for coordinated regulation. AB - Aspergillus niger secretes three glycosylated glycosyl hydrolases which are involved in degradation of the plant cell wall polysaccharide L-arabinan: alpha-L arabinofuranosidases (ABF) A and B, and endo-1,5-alpha-L-arabinase (ABN) A. The nucleotide sequence of the previously cloned gene encoding ABF A (abfA) from A. niger was determined. The coding region contains seven introns. Mature ABF A comprises 603 amino acids with a molecular mass of 65.4 kDa as deduced from the nucleotide sequence. The secreted enzyme is N-glycosylated. The primary structures of the three A. niger arabinases characterized lack similarity. Regulation of arabinase expression upon induction by sugar beet pulp and by L arabitol was studied as a function of time. This was done in wild-type A. niger as well as in transformants carrying multiple copies of either one of the ABF encoding genes. Each arabinase gene responded differently upon a mycelial transfer to L-arabitol-containing medium. Extra copies of abfA or abfB led to a decreased expression level of ABN A, though the repression elicited by abfB is stronger and more persistent than that effected by abfA. Multiple copies of both abf genes influence expression of the other ABF similarly, but to a far less pronounced degree than they affect ABN A synthesis. Four putative promoter elements, shared by all three arabinase genes, could be involved in coordination of L-arabinan degradation by A. niger. PMID- 8000539 TI - Fatty acid biosynthesis in novel ufa mutants of Neurospora crassa. AB - New mutants of Neurospora crassa having the ufa phenotype have been isolated. Two of these mutants, like previously identified ufa mutants, require an unsaturated fatty acid for growth and are almost completely blocked in the de novo synthesis of unsaturated fatty acids. The new mutations map to a different chromosomal location than previously characterized ufa mutations. This implies that at least one additional genetic locus controls the synthesis of unsaturated fatty acids in Neurospora. PMID- 8000540 TI - Isoenzymes of manganese-dependent peroxidase and laccase produced by the lignin degrading basidiomycete Ceriporiopsis subvermispora. AB - The white-rot basidiomycete Ceriporiopsis subvermispora produces two families of ligninolytic enzymes, namely manganese-dependent peroxidases (MnPs) and laccases, when growing in liquid cultures of defined composition. In medium containing 11 p.p.m. of Mn(II), up to seven isoenzymes of MnP and four isoenzymes of laccase were resolved by isoelectrofocusing (IEF), with pI values in the range 4.10-4.60 and 3.45-3.65, respectively. Occasionally, a fifth laccase isoform of pI 4.70 was also detected. In cultures with 25 and 40 p.p.m. of Mn(II), mainly the MnPs with higher pI values are produced. The isoenzyme pattern of MnP is not altered throughout the growth period of the fungus. MnP and laccase are also produced by C. subvermispora when growing on wood chips of Pinus radiata. Highest levels of both enzymes were obtained during the first week of incubation. A second peak of MnP activity was observed during the fourth week, whereas very low levels of laccase were extracted from the chips after the second week of growth. IEF analysis showed that the pI values of these laccases are similar to those of laccases produced in liquid cultures, being in the range 3.45-3.65. In contrast, four isoforms of MnP were resolved during the first week of incubation on wood chips, with pI values of 4.40, 4.17, 4.04 and 3.53. This profile underwent a transition during the second week of growth, at the end of which isoforms of MnP with pI values of 3.53, 3.40, 3.30 and 3.20 were resolved by IEF.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8000541 TI - The nematophagous fungus Verticillium chlamydosporium produces a chymoelastase like protease which hydrolyses host nematode proteins in situ. AB - The nematophagous fungus Verticillium chlamydosporium secreted several proteases in submerged culture in which soya peptone was the sole carbon and nitrogen source. One protease, VCP1 (M(r) 33,000, pI 10.2), was purified 14-fold from culture filtrates to apparent homogeneity using preparative isoelectric focusing in free solution, and shown to rapidly hydrolyse the chymotrypsin substrate Suc (Ala)2-Pro-Phe-pNA and elastin. VCP1 had a Km for Suc-(Ala)2-Pro-Phe-pNA of 4.3 x 10(-5) M and a kcat of 5.8 s-1. It was highly sensitive to PMSF and TPCK, but only moderately sensitive to chicken egg-white and soya bean trypsin inhibitors. VCP1 degraded a wide range of polymeric substrates, including Azocoll, hide protein, elastin, casein and albumin, and accounted for most of the non-specific protease activity detected in culture filtrates. The purified enzyme hydrolysed proteins in situ from the outer layer of the egg shell of the host nematode Meloidogyne incognita and exposed its chitin layer. VCP1 was secreted by several isolates of V. chlamydosporium and V. lecanii, pathogens of nematodes and insects respectively, but not plant-pathogenic species of Verticillium. These observations suggest that VCP1 or similar enzyme(s) may play a role in the infection of invertebrates. PMID- 8000542 TI - Identification and molecular cloning of four cysteine proteinase genes from the pathogenic protozoon Trichomonas vaginalis. AB - The parasitic protozoon Trichomonas vaginalis produces multiple forms of cysteine proteinase (CP). The molecular basis for this has now been examined by cloning DNA fragments encoding CPs. Using generic degenerate oligonucleotide primers based on two well-conserved regions within the central region of all eukaryotic CPs, several polymerase chain reaction fragments were isolated from T. vaginalis genomic DNA and shown to encode different CPs. One fragment with a well represented sequence was used as a general probe to screen a T. vaginalis cDNA library at moderate stringency and five different cDNA clones were isolated. Preliminary sequencing showed that they encoded similar but distinct CPs. In the process of confirming the 5' end of one of these cDNA clones using RACE-PCR (rapid amplification of cDNA 5' ends-polymerase chain reaction), an additional sequence encoding a different CP was identified. The corresponding clone (TvCP3) and the three longest clones from the library screen (TvCP1, TvCP2 and TvCP4) were characterized further. TvCP1 and TvCP2 were full-length and TvCP3 and TvCP4 were apparently slightly less than full-length. Comparison of the predicted amino acid sequences of the four clones showed that TvCP1 and TvCP4 are related (72% identity). TvCP2 is closer to TvCP1 (60%) and TvCP4 (65%) than is TvCP3, which has 53%, 59% and 56% identity to TvCP1, TvCP2 and TvCP4, respectively. Comparison with the sequences of other known CPs indicated that the T. vaginalis gene products all belong to the cathepsin L/cathepsin H/papain branch of the papain superfamily. The TvCP1, TvCP2 and TvCP4 sequences are related (38-45% identity) to those of CP2 of Dictyostelium discoideum, human cathepsin L, three CPs from lobster and CPs from black gram, oilseed rape and rice (oryzains alpha and beta). TvCP3 shows less identity to the other eukaryotic CPs but is most similar to D. discoideum CP2 (38%). The four predicted amino acid sequences share some features distinct from the majority of CPs, which suggests they might have had a common evolutionary origin. The most striking feature of sequences TvCP1, TvCP2 and TvCP3 is the apparent lack of a pre-sequence (signal sequence) for TvCP1 and very short pre-sequences for TvCP2 and TvCP3. Southern analysis indicated that the organization of the genes corresponding to the TvCP cDNAs differs. The TvCP1, TvCP2 and TvCP3 genes are single-copy, whereas the TvCP4 gene appeared to be multiple-copy.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8000543 TI - Cloning and sequencing show that 4-hydroxybenzoate hydroxylase (PobA) is required for uptake of 4-hydroxybenzoate in Rhizobium leguminosarum. AB - Mutants of Rhizobium leguminosarum bv. viciae MNF300 and R. leguminosarum bv. trifolii WU95 unable to accumulate 4-hydroxybenzoate lack 4-hydroxybenzoate hydroxylase. The capacity of these mutants to take up and grow on 4 hydroxybenzoate was restored by a 2.0 kb EcoRI-PstI DNA fragment. This contained only one ORF which had over 60% DNA sequence similarity with the structural gene for 4-hydroxybenzoate hydroxylase (pobA) from Pseudomonas spp. and Acinetobacter. Reported effects of metabolic inhibitors and substrate analogues on the apparent uptake of 4-hydroxybenzoate have now been shown to be due to their direct effect on 4-hydroxybenzoate hydroxylase. We propose that uptake of 4-hydroxybenzoate is via a metabolic 'drag' mechanism dependent on the activity of the pobA gene product. PMID- 8000544 TI - Identification of chromosomal genes located downstream of dctD that affect the requirement for calcium and the lipopolysaccharide layer of Rhizobium leguminosarum. AB - In Rhizobium leguminosarum both the C4-dicarboxylate transport system and wild type lipopolysaccharide layer (LPS) are essential for nitrogen fixation. A Tn5 mutant (RU301) of R. leguminosarum bv. viciae 3841, was isolated that is only able to synthesize LPS II, which lacks the O-antigen. Strain RU301 exhibits a rough colony morphology, flocculates in culture and is unable to swarm in TY agar. It also fails to grow on organic acids, sugars or TY unless the concentration of calcium or magnesium is elevated above that normally required for growth. The defects in the LPS and growth in strain RU301 were complemented by a series of cosmids from a strain 3841 cosmid library (pRU3020-pRU3022) and a cosmid from R. leguminosarum bv. phaseoli 8002 (pIJ1848). The transposon insertion in strain RU301 was shown to be located in a 3 kb EcoRI fragment by Southern blotting and cloning from the chromosome. Sub-cloning of pIJ1848 demonstrated that the gene disrupted by the transposon in strain RU301 is located on a 2.4 kb EcoRI-PstI fragment (pRU74). R. leguminosarum bv. viciae VF39-C86, which is one of four LPS mutants previously isolated by U. B. Priefer (1989, J Bacteriol 171, 6161-6168), was also complemented by sub-clones of pIJ1848 but not by pRU74, suggesting the mutation is in a gene adjacent to that disrupted in strain RU301. Complementation and Southern analysis indicate that the region contained in pIJ1848 does not correspond to any other cloned Ips genes. Two dctA mutants, RU436 and RU437, were also complemented by pIJ1848 and pRU3020. Mapping of pIJ1848 and Southern blotting of plasmid-deleted strains of R. leguminosarum revealed that dctD and the region mutated in strain RU301 are located approximately 10 kb apart on the chromosome. Analysis of homogenotes demonstrated that there is not a large region important in calcium utilization, organic acid metabolism or LPS biosynthesis located between the gene disrupted in strain RU301 and dctD. Strain VF39C-86 also required an elevated concentration of calcium for growth on succinate, while strains mutated in the alpha-chromosomal or beta plasmid group of Ips genes grew at the same calcium concentrations as the wild type, demonstrating that the additional calcium requirement is not a property of all LPS rough mutants. Strain RU301 nodulates peas, but does not reduce acetylene, demonstrating that the gene mutated in this strain is essential for nitrogen fixation. PMID- 8000545 TI - Insertion sequence IS1137, a new IS3 family element from Mycobacterium smegmatis. AB - A new insertion sequence (IS) has been isolated from Mycobacterium smegmatis. It is 1361 bp long and possesses characteristics of the IS3 family elements. It harbours 32 bp imperfect inverted repeats at its extremities and a 3 bp direct repeat flanks the element, possibly as the result of a transposition event. This IS, IS1137, contains three major ORFs. Two of them, ORF A and ORF B show homologies both at the amino acid sequence level and at the organization level with the ORFs encoding the transposase of the IS3 family elements. IS1137 has a narrow host range and was found only in M. smegmatis and M. chitae. The fact that IS1137 is not present in the M. tuberculosis complex strains makes this element a new candidate for transposon mutagenesis in mycobacteria. PMID- 8000546 TI - The ribosomal RNA (rrn) operons of fast-growing mycobacteria: primary and secondary structures and their relation to rrn operons of pathogenic slow growers. AB - The two ribosomal RNA (rrn) operons (rrnA and rrnB) of Mycobacterium smegmatis were investigated. The leader regions, part of the 16S rRNA genes, the spacer-1 regions, part of the 23S rRNA genes, and the spacer-2 regions were amplified by PCR or by inverse PCR and the products were cloned and sequenced. No differences in the sequences of the two operons were detected downstream from the Box A antitermination element of the leader region. Upstream from Box A a slow-grower like Box B antitermination element was found in rrnA but not in rrnB. Primer extension experiments revealed that the start of transcription lies at least 370 nucleotides upstream from the 5'-end of the 16S rRNA gene and an RNase processing site near to the Box A element. Secondary structures were deduced for pre-16S rRNA and pre-23S rRNA which are distinct from, but closely related to, the corresponding structures of slow-growing mycobacteria. On the basis of these results it is proposed that the emergence of the slow-growers from the main mycobacterial line was coincident with the deletion of a segment of DNA spanning an rrnB-like operon, leaving an rrnA-like operon as the sole source of rRNA. An explanation is also proposed for the need for two Box A motifs in the transcription of an rrn operon based on competition between the polymerase and the nascent 30S subunit for either protein S10 and/or Box A sequences. PMID- 8000547 TI - Pulsed-field gel electrophoresis analysis of the genome of amino acid producing corynebacteria: chromosome sizes and diversity of restriction patterns. AB - A large number of species of corynebacteria are known to be amino acid producers, including members of the genera Corynebacterium and Brevibacterium. Pulsed-field gel electrophoresis (PFGE) of DNA fragments obtained by using endonucleases which recognize AT-rich hexanucleotide or octanucleotide sequences produces a discrete pattern of bands useful for fingerprinting and physical mapping of the chromosome. Using Pacl and Swal endonucleases the genome of Brevibacterium lactofermentum ATCC 13869 (genome size 3052 kb) was consistently cut into 26 and 20 bands, respectively, and the genome of Corynebacterium glutamicum ATCC 13032 (2987 kb) yielded 27 and 26 fragments, respectively. The pattern of restriction fragments was identical for related strains (B. lactofermentum ATCC 13869, B. lactofermentum BLO, B. lactofermentum R31) but different from the pattern of fragments of other soil isolates of the same species (B. lactofermentum DSM 20412) or from closely related organisms such as C. glutamicum; the different pattern of restriction fragments may be used to differentiate taxonomically related species. Brevibacterium linens showed a different behaviour, due to its high G+C content; its genome (3105 kb) was resolved into 8 or 15 fragments, respectively, by digestion with the hexanucleotide-recognizing endonucleases DraI and AseI. PFGE of DNA fragments obtained using these enzymes is a powerful technique for quick resolution of the corynebacteria genome into a small number of large fragments. PMID- 8000548 TI - In situ probing of gram-positive bacteria with high DNA G + C content using 23S rRNA-targeted oligonucleotides. AB - 23S-rRNA-targeted oligonucleotide probes were designed for the phylogenetic group 'Gram-positive bacteria with high G + C content of DNA' (GPBHGC). A sequence idiosyncrasy in two adjacent base pairs in the stem of helix 69 in domain IV of the 23S rRNA is present in all hitherto analysed strains of GPBHGC. An oligonucleotide probe targeted to this region hybridized only with strains of GPBHGC and was successfully used for in situ monitoring of these cells in activated sludge. Another unique feature of the 23S rRNA molecules of GPBHGC is a large insertion in domain III. Fluorescent oligonucleotides targeted to the highly variable regions of the rRNA within the insertions of Corynebacterium glutamicum DSM 20300, Aureobacterium testaceum DSM 20166 and Brevibacterium sp. DSM 20165 hybridized specifically to their target strains, whereas probing with oligonucleotides complementary to the rRNA-coding strand of the 23S rDNA and to the spacer between 16S and 23S rRNA of C. glutamicum did not result in detectable fluorescence. This confirmed that the large 23S insertions are indeed present in 23S rRNAs of GPBHGC and provide potential target sites for highly specific nucleic acid probes. PMID- 8000549 TI - Permeabilization of mycolic-acid-containing actinomycetes for in situ hybridization with fluorescently labelled oligonucleotide probes. AB - The application of whole-cell hybridization using labelled oligonucleotide probes in microbial systematics and ecology is limited by difficulties in permeabilizing many Gram-positive organisms. In this investigation paraformaldehyde treatment, acid methanolysis and acid hydrolysis were evaluated as a means of permeabilizing mycolic-acid-containing actinomycetes prior to hybridization with a fluorescently labelled oligonucleotide probe designed to bind to a conserved sequence of bacterial 16S rRNA. Methods were evaluated on stationary-phase cultures of Gordona bronchialis, Mycobacterium fortuitum, Nocardia asteroides, N. brasiliensis, Rhodococcus equi, R. erythropolis, R. fascians, R. rhodochrous and Tsukamurella paurometabola, none of which could be probed following 4% (w/v) paraformaldehyde fixation. For comparison and to test the general applicability of mild acid pretreatments, Bacillus subtilis, Lactobacillus plantarum, Escherichia coli and Pseudomonas putida were also studied. The data showed that most of the mycolic-acid-containing organisms were successfully permeabilized by mild acid hydrolysis in 1 M HCl at 37 degrees C. Cells were treated for different lengths of time. In general, the mycolic-acid-containing organisms required between 30 and 50 min hydrolysis, whereas B. subtilis, E. coli and P. putida were rendered permeable in only 10 min. Interestingly, L. plantarum could not be permeabilized using acid hydrolysis even after 60 min exposure to 1 M HCl. PMID- 8000550 TI - A numerical phenotypic taxonomic study of the genus Neisseria. AB - A numerical phenotypic taxonomic study of 315 strains of Neisseria and some allied bacteria examined for 155 phenotypic tests showed 31 groups, most of which were reasonably distinct. These fell into four major areas. Areas A, B and C contained species of Neisseria, whereas area D contained the organisms known as 'false neisserias' together with Branhamella, Moraxella and Kingella species. Area A contained N. gonorrhoeae (which showed two subgroups), N. meningitidis (with two subgroups, and N. cinerea closely associated), N. polysaccharea, N. elongata subsp, glycolytica and N. lactamica. Area B contained mainly organisms from the human nasopharynx, and the nine groups were not very distinct: only three, N. mucosa, N. perflava and N. sicca could be recognized by the presence of type strains, and there was little relationship between taxonomic position and species epithets. Area C contained several groups from animals, N. animalis, N. canis and two phenons that may be justified as new species of Neisseria, one from lizards and the other from dental plaque of herbivores. Area C also contained N. elongata, N. subflava (with N. flavescens), type strain of Morococcus cerebrosis and the CDC groups M-5 (N. weaveri) and EF-4. Area D contained Branhamella catarrhalis, a combined group which consists of strains of the 'false neisserias' N. caviae and N. cuniculi, the 'false neisseria' N. ovis, and a group of Moraxella strains. A small group representing Kingella kingae is included in area D. Mean test error was 1.7%. PMID- 8000551 TI - Adherence of Ureaplasma urealyticum to human epithelial cells. AB - Adherence of Ureaplasma urealyticum cells to eukaryotic cell monolayers was quantified using the Bertholet assay to monitor ammonia produced from urea by ureaplasma urease. Adherence was abolished by pre-treatment of ureaplasmas with HeLa cell extracts and inhibited to varying degrees by pretreatment of the ureaplasmas with N-acetylneuraminic acid, specific antisera and monoclonal antibodies. The data suggest the presence of several ureaplasma adhesins, some of which are species- or serotype-specific and some of which are proteinaceous and antigenic. The serotype-8-specific 96 kDa surface-expressed antigen may be one adhesin. Pre-treatment of HeLa cell monolayers with neuraminidase significantly reduced ureaplasma adherence and, using a novel 'immunoblot adherence assay', ureaplasmas were shown to bind to a number of HeLa cell components, three of which appear to terminate in sialic acid. PMID- 8000552 TI - The susceptibility of S-layer-positive and S-layer-negative Aeromonas strains to complement-mediated lysis. AB - Forty strains of Aeromonas hydrophila and Aeromonas veronii recovered from invasive and non-invasive infections were tested for their susceptibility to complement-mediated lysis by 65% pooled human serum (PHS). Based upon the results of this assay, two major populations could be defined. The first group (n = 20) consisted of serogroup O:11 strains, all of which possessed a paracrystalline surface layer (S layer); all of these strains were refractory to the bactericidal activity of 65% PHS with the exception of A. hydrophila strain AH-121, which was composed of mixed subpopulations of serum-susceptible and serum-resistant clones. A second collection of isolates (n = 20), all of which were S-layer-negative, contained a subgroup of strains (n = 7) that were highly susceptible to complement-mediated lysis, showing a greater than 100-fold reduction of viable progeny within 30 min of exposure to 65% PHS. Serum-resistant strains from both groups could not be lysed by exposure of bacterial cells to polyclonal somatic or whole cell antisera or to 30 micrograms ml-1 of polymyxin B nonapeptide prior to challenge with 65% PHS. Analysis of selected serum-resistant and serum susceptible strains from both groups showed that all isolates activated the complement pathway and most bound C3b to the cell surface, indicating that the inability of complement to lyse serum-resistant strains was related to a defect in the terminal portions of the complement pathway.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8000553 TI - Human papillomavirus infection. PMID- 8000554 TI - Therapy for attention-deficit hyperactivity disorder. PMID- 8000555 TI - A clinical approach to alternative medicine. AB - Our patients receive and will continue to receive alternative therapies regardless of our stand on the issue. While scientific scrutiny may slowly bring a few of them into the medical mainstream, the number of alternative techniques is unlikely to dwindle significantly. Primary care physicians can help their patients deal with them by knowing the local alternative medical community, by gentle counseling about the potential for harm in certain techniques, and by steering patients toward practitioners with a reasonable scope of practice that matches the patient's belief system. In this way, the physician may confidently support the patient's belief in the healing power of whatever therapy- alternative or traditional--is chosen. PMID- 8000556 TI - Unrecognized mental illness in primary care. Another day and another duty in the life of a primary care physician. PMID- 8000557 TI - Environmental tobacco smoke. Health effects and prevention policies. Council on Scientific Affairs, American Medical Association. AB - The US Environmental Protection Agency report released in January 1993, Respiratory Health Effects of Passive Smoking: Lung Cancer and Other Disorders, has stirred considerable discussion and interest in the issues surrounding tobacco and health. The report addresses major health effects of environmental tobacco smoke (ETS), concluding (1) that ETS is causally associated with lung cancer in nonsmoking adults and should be classified as a group A, or known human carcinogen, with approximately 3000 excess deaths yearly; (2) that ETS produces an increased risk of development of acute lower respiratory tract irritation, asthma, and acute lower respiratory tract infections in children exposed in the home; and (3) that ETS is associated with an increase risk of sudden infant death syndrome. Other studies implicate ETS in between 35,000 and 40,000 premature deaths each year from cardiovascular disease. The Council on Scientific Affairs (CSA) agrees that ETS should be classified as a human carcinogen, and strongly supports the findings of other groups concerning both lung cancer and ETS-induced respiratory tract illnesses in children. The CSA concludes that exposure to passive smoke, whether in utero or during infancy, is associated with an increased risk of sudden infant death syndrome. The CSA agrees that the available evidence suggests that ETS exposure leads to increased risk for cardiovascular disease. It is clear that these morbidity and mortality estimates represent a significant public health threat that demands attention from the health community as well as government regulatory agencies involved with health protection. PMID- 8000558 TI - Passive smoke and low birth weight. Evidence of a threshold effect. AB - OBJECTIVE: To examine the relationship between different levels of maternal passive tobacco smoke exposure and low-birth-weight infants. DESIGN: Data from the National Health Interview Survey were analyzed. PARTICIPANTS: Women who did not smoke during pregnancy and gave birth to children within 6 years of the date of the interview in 1988 were the source of the data (N = 3253). Passive smoke exposure was categorized as very low, low, moderate, and high. MAIN OUTCOME MEASURES: Low-birth-weight (< 2500 g) infants and mean birth weight in grams. RESULTS: There was no significant difference in the rates of low birth weights when passive smoke exposure was dichotomized as no exposure vs some exposure (5.0% vs 5.6%, respectively; P = .55). However, when the level of exposure to passive smoke was considered as a continuum, high exposure was associated with both lower mean birth weights in grams (P = .007) and a greater likelihood of a low birth weight (P = .01), indicating a threshold effect of exposure. Logistic regression analysis indicated that, after controlling for potentially confounding variables, individuals with high exposure are 1.57 times (95% confidence interval [CI], 0.98 to 2.51) as likely as those with low exposure to have a low-birth weight infant. Among nonwhites, individuals with high exposure to passive smoke were 2.31 times (95% CI, 1.06 to 4.99) as likely to have a low-birth-weight infant as those with low exposure to passive smoke. CONCLUSION: A threshold effect of exposure to passive smoke and low birth weight was discovered. PMID- 8000559 TI - Hypnosis and conversion of the breech to the vertex presentation. AB - OBJECTIVE: To evaluate the effectiveness of hypnosis to convert a breech presentation to a vertex presentation. DESIGN: Prospective case series compared with historical, matched comparison group. SUBJECTS: One hundred pregnant women whose fetuses were in breech position at 37 to 40 weeks' gestation and a matched comparison group of women with similar obstetrical and sociodemographic parameters derived from databases for other studies from the same time period and geographical areas. INTERVENTION: The intervention group received hypnosis with suggestions for general relaxation with release of fear and anxiety. While in the hypnotic state women were asked for the reasons why their baby was in the breech presentation. As much hypnosis was provided as was convenient and possible for the women until they were delivered of the baby or the baby converted to the vertex position. MAIN OUTCOME VARIABLES: A successful conversion for the intervention group was scored when the baby spontaneously converted to the vertex position before delivery or successful external cephalic version. The conversion rate of the intervention group was compared with the comparison group who received standard obstetrical care without the opportunity for hypnosis. DATA ANALYSIS: Parametric testing of statistically significant differences in the rate of conversion between the two groups. RESULTS: Eighty-one percent of the fetuses in the intervention group converted to vertex presentation compared with 48% of those in the comparison group. This difference was statistically significant. CONCLUSIONS: Motivated subjects can be influenced by a skilled hypnotherapist in such a manner that their fetuses have a higher incidence of conversion from breech to vertex presentation. Psychophysiological factors may influence the breech presentation and may explain this increased frequency of conversion to vertex presentation. PMID- 8000560 TI - Overweight women delay medical care. AB - OBJECTIVE: To determine whether women delay or avoid necessary health care because they are overweight. DESIGN: Observational study using a self administered survey. SETTING: A 250-bed community hospital in La Crosse, Wis. PARTICIPANTS: All female nurses, nursing assistants, health unit coordinators, and general psychiatric assistants who were employed full- or part-time at the community hospital in July 1992. We received 310 (76%) responses from 409 potential respondents. MEASUREMENTS/MAIN RESULTS: Overall, 12.7% of respondents reported delaying or canceling a physician appointment because of weight concerns. Another 2.6% kept their appointments but refused to be weighed. Only body mass index was significantly associated with appointment cancellation. The odds ratio of an obese woman (body mass index in excess of 27) delaying medical care was 3.885 (95% confidence interval, 1.509 to 10.274). CONCLUSION: Obese women commonly delay health care because of weight concerns. PMID- 8000561 TI - Human immunodeficiency virus infection care is unavailable to inmates on release from jail. AB - BACKGROUND: The human immunodeficiency virus (HIV) seroprevalence in urban jails is higher than that in the general community. METHODS: We interviewed a cohort of HIV-infected inmates in a jail in New York, NY, during incarceration and after release to assess the accessibility of medical and social services. RESULTS Of the 170 inmates who were interviewed and released into the community, 40 (24%) came to a follow-up interview. Of the 40, 25 (62%) had not received an appointment with an infectious disease clinic by the time of the new interview. Only eight (27%) of the 32 who received zidovudine in jail obtained zidovudine; and only one of the 13 who received isoniazid prophylaxis in jail obtained isoniazid prophylaxis. Twenty (65%) had applied for but not yet received Medicaid. CONCLUSION: Inmates infected with HIV may encounter difficulties obtaining medical care and social services on release into the community, which can potentially lead to active infectious tuberculosis. Family physicians may encounter HIV-positive patients who are newly released from jail and who need follow-up medical care, and they must help address the needs of HIV-positive, formerly incarcerated people. PMID- 8000562 TI - Psychosocial interest, medical interviews, and the recognition of depression. AB - OBJECTIVES: To measure primary care physicians' attitudes toward psychosocial issues, determine their relationship to the style of the medical interview, and assess whether attitudes and interview behaviors lead to correct diagnosis in patients with depression. DESIGN: Physicians were videotaped while interviewing four patients standardized with criteria symptoms of major depression. Physicians were unaware of the mental health focus of the study. SETTING: Patient examining rooms. PARTICIPANTS: Physicians were eligible for recruitment if they were board certified or eligible in family practice or internal medicine, practiced primary care medicine, and were listed in regional directories. Standardized patients were recruited from the community. MAIN OUTCOME MEASURES: Attitudes toward psychosocial issues (measured by the Physician Belief Scale), interview content (measured by review of the videotaped encounters), interview behaviors (measured by the Interaction Analysis System for Interview Evaluation), and a listing of depression in the differential diagnosis (determined by physician debriefing interviews). RESULTS: Forty-seven community-based practitioners participated. Forty-eight percent of interviews resulted in a diagnosis of depression. Physician Belief Scale scores were not significantly correlated with patient centered interviewing, psychosocial questions, inquiry about depression symptoms, or a depression diagnosis. Longer interviews were more likely to result in a depression diagnosis. CONCLUSIONS: High interest in psychosocial issues was not associated with patient-centered interviewing behaviors, questions about psychosocial or depression symptoms, or depression diagnoses. However, certain patient-centered interviewing behaviors, particularly those defined as "affective," did lead to the recognition of depression. PMID- 8000563 TI - A review of unrecognized mental illness in primary care. Prevalence, natural history, and efforts to change the course. AB - Studies of the prevalence, natural history, and outcome of unrecognized mental illness in general medical outpatient settings were reviewed. Approximately half of the patients with a psychiatric disorder were not recognized as having a mental illness by their primary care physician. The natural history of unrecognized mental illness suggests a poorer clinical course of anxiety disorders but not for depressive disorders. Most interventions demonstrated a significant improvement in the physician's ability to identify and treat psychiatric disorders but had a minimal effect on patient symptoms and no effect on short-term health care use. Although primary care physicians do not recognize psychiatric disorders in a high percentage of patients, efforts to improve recognition may not lead to decreased patient suffering or decreased health care costs. PMID- 8000564 TI - In situ hybridization of trkB and trkC receptor mRNA in rat forebrain and association with high-affinity binding of [125I]BDNF, [125I]NT-4/5 and [125I]NT 3. AB - The TrkB and TrkC receptor tyrosine kinases have been identified as high-affinity receptors for the neurotrophic factors brain-derived neurotrophic factor (BDNF) and neurotrophin-4/5 (NT-4/5) and NT-3 respectively. These receptor classes were identified and mapped by the in situ hybridization of antisense riboprobes complementary to portions of the intracellular (tyrosine kinase) or extracellular (ligand-binding) domains of trkB and trkC mRNA, and by the distribution of high affinity [125I]BDNF, [125I]NT-4/5 and [125I]NT-3 binding sites in adjacent rat brain sections. Both methods showed that TrkB and TrkC receptors are abundant and widely expressed throughout the brain. Kinase or extracellular domain trkC probes labelled neuronal somata in a qualitatively similar manner in virtually every major area of the forebrain. Neither trkC probe labelled non-neuronal cells except for elements within cerebral arteries and arterioles. The kinase domain trkB probe hybridized exclusively to neurons. Neurons expressing trkB were even more widely distributed than those expressing trkC. The extracellular domain trkB probe labelled neurons with the same relative distribution as the trkB kinase domain probe, but also hybridized extensively with non-neural cells, particularly astrocytes, ependyma and choroid epithelium cells. The distribution of [125I]NT-3 binding sites generally resembled that of trkC hybridization, particularly in the neocortex, striatum and thalamus. [125I]BDNF and [125I]NT-4/5 binding sites were more widely distributed and denser than those for [125I]NT-3, and resembled the trkB hybridization pattern. These patterns are consistent with the preferential binding in the brain of TrkC receptors by [125I]NT-3 and of TrkB receptors by [125I]BDNF and [125I]NT-4/5. That the predominantly neuronal patterns of hybridization obtained with kinase and extracellular domain probes for trkC are qualitatively indistinguishable suggests that truncated and full-length forms of TrkC are expressed within extensively overlapping populations of neurons. In marked contrast to TrkC, expression of the full-length and truncated forms of TrkB appears to be largely segregated, being expressed principally on neurons and non-neuronal cells respectively. The abundant and widespread neuronal distribution of full-length, signal-transducing forms of TrkB and TrkC predict that their cognate ligands, BDNF, NT-4/5 and NT-3, may exert direct effects on a large proportion of neurons within the mature brain. PMID- 8000565 TI - Voltage-gated currents in rabbit retinal astrocytes. AB - The voltage-gated currents of the astrocytes associated with the retinal capillaries of the rabbit retina were studied using whole-cell patch clamp recording. The resting potential of these cells was -70 +/- 4.8 mV (mean +/- SEM; n = 54), and the input resistance and cell capacitance were 558 +/- 3.6 M omega and 19.5 +/- 1.8 pF respectively. Depolarization to potentials positive to -50 mV evoked rapidly activating inward and outward currents. The inward current was transient, eliminated by substitution of choline for Na+ in the bathing solution, and reduced by 50% in the presence of 1 microM tetrodotoxin. The time-to-peak of the Na+ current was more than twice that for the Na+ current found in retinal neurons. The glial Na+ current was half-inactivated at -55 mV. A transient component of the outward K+ current was blocked by external 4-aminopyridine while a more sustained component was blocked by external tetraethylammonium. At potentials between -150 and -50 mV the membrane behaved Ohmically. Voltage-gated currents in retinal astrocytes recorded in situ appear qualitatively similar to those described for some glial cells in vitro. PMID- 8000567 TI - The presynaptic cell determines the number of synapses in the Drosophila optic ganglia. AB - The role of the pre- and postsynaptic cells in determining the number of synapses has been investigated in retina mosaics of the gigas (gig) mutant of Drosophila. Mutant photoreceptors are two to three times larger than those of the wild type, while adjacent cells in the mosaic retina and the lamina are normal in size. Serial electron microscope reconstructions of mosaic lamina cartridges show that gig photoreceptors establish more synapses upon lamina neurons than the normal photoreceptors do. By contrast, the number of feedback synapses that lamina neurons make onto gig photoreceptors does not increase. The increment in the number of synapses correlates positively with the increment of presynaptic cell membrane, resulting in constancy of synapse density. The phototactic response of flies bearing a gig eye is abnormal, indicating that the extra synapses are functional. PMID- 8000566 TI - A neurotoxic prion protein fragment induces rat astroglial proliferation and hypertrophy. AB - Prion-related encephalopathies are characterized by the accumulation of an abnormal prion protein isoform (PrPSc) and the deposition of PrP amyloid in the brain. This process is accompanied by neuronal loss and astrogliosis. We recently showed that a synthetic peptide corresponding to residues 106-126 of human PrP is amyloidogenic and causes neuronal death by apoptosis in vitro. In the present study we investigated the effects of 1- and 14-day exposures of rat astroglial cultures to micromolar concentrations of this peptide as well as peptides homologous to other portions of PrP, a peptide corresponding to residues 25-35 of amyloid-beta protein, and a scrambled sequence of PrP 106-126. No significant changes were observed after 1-day exposure of cultures to any peptide. Conversely, 14-day treatment with PrP 106-126 (50 microM) resulted in a 5-fold increase in glial fibrillary acidic protein (GFAP) expression, as evaluated by Northern and Western blot analyses, and a 1.5-fold increment in cell number. Light and electron microscopy immunohistochemistry showed an enlargement in size and density of astroglial processes, and an increase in GFAP-immunoreactive intermediate filaments. These changes were not observed after 14-day treatment of cultures with the other peptides, including PrP 106-126 scrambled. The increase in GFAP expression of astroglial cultures exposed to PrP 106-126 was quantitatively similar to that found in scrapie-infected hamster brains.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8000568 TI - Inhibitory effects of L-glutamate on central processes of crustacean leg motoneurons. AB - In crustaceans, glutamatergic excitation at the neuromuscular synapse has been extensively studied. Fewer reports exist of the central and possibly inhibitory actions of glutamate on neurons. The present study analyses the response of intracellularly identified motoneurons, which innervate the proximal leg muscles, to local glutamate pressure applications in the neuropil, in an in vitro thoracic preparation of the crayfish Procambarus clarkii. L-Glutamate application always inhibited motoneuron activity, with a decrease in input resistance. The resulting depolarization or hyperpolarization could usually be reversed within 10 mV of the resting potential. The response persisted in neurons pharmacologically isolated with Cd2+ or tetrodotoxin. The reversal potential of the response to glutamate was displaced in a low-chloride solution. Similar responses were obtained with GABA. Application of GABA blocked the glutamate response in a competitive manner. Both responses were suppressed by beta-guanidino-propionic acid, a competitive antagonist for GABA receptors. This indicates that glutamate activates a chloride GABA receptor-channel. Micromolar concentrations of picrotoxin reduced both the L glutamate and the GABA inhibitory responses, thereby unmasking a smaller, picrotoxin-resistant effect of glutamate (but not of GABA), which was excitatory and sensitive to 6,7-dinitroquinoxaline-2,3-dione (DNQX). These results suggest dual and opposite roles for motoneuron glutamatergic connections--a peripheral (well known) net excitatory one and a central net inhibitory one. Direct inhibition of motoneurons by L-glutamatergic neurons is to be expected. PMID- 8000569 TI - Polarized distribution of the trans-Golgi network marker TGN38 during the in vitro development of neocortical neurons: effects of nocodazole and brefeldin A. AB - Neurons are polarized secretory cells whose cytoplasm and plasma membrane are polarized to form two compartments: dendrites and axons. In mature, fully polarized neurons, the microtubule-associated protein Map2 is targeted to dendrites, while tau is mainly restricted to axons. However, the intraneuronal distribution of secretory pathway organelles, such as the endoplasmic reticulum and the Golgi complex, which give rise to all constitutive, regulated and lysosome vesicles, is poorly understood. Thus, to investigate the distribution of the trans-Golgi network during the development and maturation of rat neocortical neurons in vitro, we have utilized an antibody recognizing a 38 kDa trans-Golgi network-specific protein, TGN38, and immunofluorescence microscopy. Before neurons have established polarity. TGN38 immunoreactivity outlines several vesicles dispersed throughout the cell body cytoplasm; these converge close to a major Map2-immunopositive process during the establishment of neuronal polarity, and later merge into a single structure located at the base of a thick Map2 immunopositive process, approximately 18 h after plating. At this stage TGN38 immunoreactivity is located within 45 degrees of the major Map2-immunoreactive process in 54% of neurons, while in only 6% of cells it is located at the opposite pole. After 3 days in vitro, during the segregation of microtubule associated proteins to either dendrites or axons. TGN38 immunoreactivity clusters continue to be located close to a major dendrite, and in some neurons these clusters begin to enter a major Map2-immunoreactive process. At 10 days in vitro TGN38 immunoreactivity extends into a major dendrite for 5-30 microns in many neurons. Thus, the distribution of TGN38 immunoreactivity becomes polarized, being localized within a single, usually the major, neocortical dendrite. Our results also show that the morphological appearance of TGN38-immunoreactive structures is microtubule-dependent, since nocodazole treatment of polarized neurons induces scattering of TGN38-immunoreactive vesicles throughout the cell body's cytoplasm. Treatment with brefeldin A induces scattering of small TGN38 immunoreactive vesicles throughout the neuronal cytoplasm and processes, a different response to that observed in non-neuronal cells. PMID- 8000570 TI - Preserved recognition memory for small sets, and impaired stimulus identification for large sets, following rhinal cortex ablations in monkeys. AB - Seven cynomolgus monkeys (Macaca fascicularis) performed a series of tasks designed to assess their visual memory and their ability to identify visual stimuli. Preoperatively they were trained and tested in delayed and simultaneous matching-to-sample, both with a large stimulus set and with a small stimulus set; there were approximately 500 million possible stimuli in the large set, which effectively means that stimuli were trial-unique with this set, while in the small set there were only four stimuli, which appeared repeatedly in every session of training with the small set. Three of the monkeys then had the cortex within and adjacent to the rhinal sulcus removed bilaterally, while the other four served as an unoperated control group. Postoperatively, the animals with ablation of the rhinal cortex showed severe impairment in delayed matching-to sample with the large set. With the large set they were also impaired, however, in matching-to-sample with no delay between sample and test (0 s delay) and in simultaneous matching-to-sample, in which the sample and the two choice patterns were simultaneously present for inspection. The impairment in simultaneous matching-to-sample was particularly clear when the task was made more difficult by reducing the physical discriminability of the trial-unique stimuli. With the small set of four stimuli, the animals with rhinal cortex ablation were not significantly impaired in overall performance level in delayed matching-to sample, though their level was on average below that of the normal control animals. The stimulus set was then further restricted, so that there were now only two stimuli used throughout; in this condition, the animals with rhinal cortex ablation performed delayed matching-to-sample without any suggestion of impairment, showing indistinguishable performance levels from those of the control animals over a range of forgetting intervals. Subsequently, the animals were trained in trial-unique non-matching-to-sample with 0 s delay, which required reversal of the matching-to-sample rule they had previously learned; animals with rhinal cortex ablation showed a clear impairment in this rule reversal learning. The final experimental task was a concurrent discrimination learning task in which 20 pairs of stimuli were presented once per session; the animals with rhinal cortex ablation learned more slowly than the control animals on average, but the difference between the groups did not attain statistical significance.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8000571 TI - Learning-related alterations in the visual responsiveness of neurons in a memory system of the chick brain. AB - The intermediate and medial hyperstriatum ventrale (IMHV) of the chick brain is known to be essential for the learning process of imprinting. The activity of neurons was recorded from the left IMHV of 2-day-old unanaesthetized chicks while the chicks were free to move in a running wheel. The chicks were either raised in complete darkness or visually trained (imprinted) with a set duration of exposure to a visual image. The first group of these birds was trained by exposure for 100 min to a rotating red box and the second was trained by similar exposure to a rotating blue cylinder. A third group was left untrained. Training more than doubled the proportion of sites that responded to the stimulus used to train the bird, relative to the proportion of sites responsive to the other stimulus and to the proportion of sites responsive in the untrained birds; the learning-related increase was selective and highly significant. Behavioural monitoring indicated that the enhanced responsiveness could not be explained by overt differences in the alertness, attentiveness or movements of the birds. No significant effect of training was found on the proportion of sites responsive to a rotating stuffed jungle fowl or to the sound of a maternal call. The response at certain sites selectively signalled the presence of the training stimulus, while at others the response showed generalization across stimulus shape or colour. There was a non specific effect of training upon the pattern of spontaneous discharges of the neurons: the numbers of spikes occurring in clusters (bursts) was significantly reduced in trained birds compared with the dark reared controls. PMID- 8000573 TI - Defined neuronal arborizations by guided outgrowth of leech neurons in culture. AB - Identified neurons of Hirudo medicinalis were cultivated on a protein extract of the extracellular matrix (ECM) of the leech. Microscopic patterns of active ECM protein were prepared by UV photolithography using aluminium masks. The shape of the patterns was visualized by a colour pattern formed in a dye-polymer substrate. The neurons were explanted on the root of branched ECM patterns. The patterns guided the outgrowth of neurites along linear lanes and they induced a bifurcation of the neurites under certain conditions. Neurons with a reproducible, regular shape of arborization were obtained within 1-2 days. PMID- 8000572 TI - Cytosolic Ca2+ binding proteins during rat brain ageing: loss of calbindin and calretinin in the hippocampus, with no change in the cerebellum. AB - The expression of two cytosolic, high affinity Ca(2+)-binding proteins, calbindin 28 and calretinin, has been investigated in the cerebellum and hippocampus of young and old rats (from 12 days to 30 months) by combining immunofluorescence and Western blotting. Three markers, calreticulin (the major Ca2+ binding protein within the lumen of the endoplasmic reticulum), MAP-2 (a microtubule binding protein concentrated in neuronal dendrites) and synaptophysin (an integral protein of synaptic vesicles), were studied in parallel. In the cerebellar cortex a rise from 12 to 60 days was observed with calbindin-28 and, especially, calretinin, concentrated in the Purkinje and granule neurons, respectively. The level of expression of the two proteins subsequently remained high and the distribution was unchanged, even in the cerebellum of old animals. A completely different pattern was observed in the hippocampus. Here calretinin, present especially in fibres and interneurons, was abundant in the young, decreased in the adult and reached low values in the old rats. Calbindin-28 accumulated during growth, especially in a subpopulation of CA1 pyramidal cells and in the mossy fibres of CA3, then declined, although irregularly, during ageing. These changes of the two proteins were more marked in the dorsal and central parts than in the ventral part of the hippocampus. In the same brain areas the levels of expression of the three additional markers and their distribution within neurons and synapses were unchanged by ageing.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8000574 TI - Cortical layer-specific effects of the metabotropic glutamate receptor agonist 1S,3R-ACPD in rat primary somatosensory cortex in vivo. AB - The effects of iontophoretically applied (1S,3R)-1-aminocyclopentane-1,3 dicarboxylic acid (1S,3R-ACPD), a metabotropic glutamate receptor (mGluR) agonist, were studied on extracellularly recorded neurons throughout the depth of the primary somatosensory cortex in the anaesthetized adult rat. Distinct excitatory effects were found almost exclusively in neurons recorded in layer V. Postsynaptic depressant effects dominated neurons recorded in layers I-IV. In layer VI, neurons were equally divided as to excitation and depression. Both the excitatory and postsynaptic depressant effects could be antagonized by the mGluR antagonist (RS)-alpha-methyl-4-carboxyphenylglycine (MCPG). Experiments using bicuculline and several lines of analysis suggested that the postsynaptic depressant effects were mediated directly, rather than through disfacilitation. In a proportion of neurons 1S,3R-ACPD selectively depressed synaptically evoked responses (produced by vibrissa deflections), with little or no effect on the postsynaptic level of firing. Comparing the depressant effects of 1S,3R-ACPD with those of GABA supported a presynaptic mGluR site. Responses to centre and surround receptive field stimulation were depressed to the same extent, suggesting that thalamocortical and intracortical axon terminals are equally endowed with presynaptic receptors. In contrast to previous studies, the actions of L-2-amino-4-phosphonobutyric acid (L-AP4) were shown to be qualitatively different to those of 1S,3R-ACPD, in particular suggesting that the presynaptic depression produced by 1S,3R-ACPD is not mediated by L-AP4-type receptors. The functional implications of different mGluR actions in the primary somatosensory cortex are discussed. PMID- 8000575 TI - Naloxone ameliorates the learning deficit induced by pentylenetetrazol kindling in rats. AB - Endogenous opioid peptides modulate and regulate processes of central excitability. Furthermore, opioids are thought to interfere with processes of learning and memory storage. In order to study the effects of endogenous opioids on both processes we injected in the course of development of pentylenetetrazol kindling the opiate receptor antagonist naloxone, and tested the animals afterwards in a shuttle-box task. It was found that naloxone pretreatment had dissociative effects. There was no effect on seizure outcome, whereas the learning deficit was ameliorated in the kindled group. The data suggest that endogenous opioid peptides contribute to the learning deficit found in pentylenetetrazol-kindled rats. PMID- 8000576 TI - Regulatory, bioengineering and clinical requirements for cardiac valves: a new approach for a unique market. PMID- 8000577 TI - Clinical use of homologous and heterologous mitral valves. PMID- 8000578 TI - Double mitral homograft for recurrent bacterial endocarditis of the mitral and tricuspid valves. AB - A young patient suffering from acute bacterial endocarditis underwent reconstructive surgery of the mitral and tricuspid valves. One year later a recurrent endocarditis occurred that could not be controlled with antibiotic therapy. Two separate mitral homografts were used to replace both the mitral and the tricuspid valves. The homografts' papillary muscles were sutured side to side to the recipient's and a circumferential suture of the leaflet tissue was accomplished. Homograft implantation was associated with Carpentier ring annuloplasty of the atrioventricular valves. In the right sided position, the mitral homograft was oriented in an anti-anatomical manner and an inverted semi rigid prosthetic ring of the mitral type was inserted. Clinical and echocardiographic follow up at four months was excellent. PMID- 8000579 TI - Homograft mitral valve replacement--a case report. AB - This case report describes a 25-year-old patient with calcific rheumatic mitral restenosis who underwent mitral valve replacement using a fresh, antibiotic preserved mitral homograft. The technical details of the implantation are described. PMID- 8000580 TI - Mitral valve replacement with the Biocor stentless mitral valve: early results. AB - Chordal preservation during mitral valve replacement is thought to greatly preserve left ventricular function. Recently a stentless mitral valve (Biocor) became available for clinical use. It is a porcine mitral valve with the entire chordal apparatus, the sewing ring being reinforced by a bovine pericardial ring and the chordae being sutured together onto two pericardial patches. During a six months period, seven patients undergoing mitral valve replacement for mitral insufficiency (four cases), mitral stenosis (two cases) or mixed lesions (one case) received a stentless mitral valve. Their mean age was 66.3 +/- 4.8. The valve was implanted by suturing the pericardial patches onto the papillary muscles and the sewing ring onto the mitral annulus. Echocardiography control immediately after surgery showed good valve function. Three valves failed after a period of seven days, seven and 12 months respectively. The valve lesions were similar and consistent with an excessive tension on the chordae and on the valvular tissue. There were tears along the posterior annulus and at the level of the commissures, often accompanied by chordal rupture. Histology and scanning electron microscopy showed good integration of the prosthesis with the patients own tissues. There were areas of overgrowing tissue without endothelial cells especially in the area of papillary muscle -pericardial patch interaction. The remaining four patients continue to do well after a mean follow up of two years. The apparent excessive tension on the valve tissues leading to the premature failure of the prosthesis could be due to the variability in the distance between mitral annulus and papillary muscles.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8000581 TI - Mitral annular function assessed by 3D imaging for mitral valve surgery. AB - We developed a surgical technique for mitral valve reconstruction without a prosthetic ring. This procedure may have two advantages. One is avoidance of the potential thrombogenicity of the prosthetic ring, and the other is that this procedure may maintain the normal function of mitral annulus. To clarify the latter advantage, we defined a method for 3D assessment of the heart, especially for the dynamic changes of the mitral annulus. 3D images of the heart, including both mitral and tricuspid annuli in eight phases during the cardiac cycle, were reconstructed from magnetic resonance images of seven normal subjects, and used for this study. To depict the changes in the annular shape, we determined the following parameters of the annular function: (a) annular excursion, (b) direction of motion (direction cosine) and (c) orientation of the annulus (direction cosine) for the annular motion, (d) annular area and (e) displacement of the anterior portion from the approximated plane of the annulus. The data for the systolic annular motion indicate that the mitral annulus moves towards the apex with slight caudal deviation, with the excursion of 12.1 mm. The change in annular orientation indicates that the mitral annulus shows translational motion during systole. The mitral area was reduced by 25.6% (n = 5) from mid-diastole to mid-or late systole. Displacement at the anterior portion of the annulus did not change markedly during systole. The results demonstrate the physiologic function of the mitral annulus in normal subjects. This method will be applied to the clinical study of mitral valve reconstruction surgery. Based on the differences in annular length in intact and excised states, we describe the intact state of the posterior leaflet as "natural redundancy." Restoration of this natural redundancy has been a hallmark of successful mitral repair for over 20 years. PMID- 8000582 TI - Anatomic basis for mitral valve modelling. AB - The increasing popularity of mitral valve repair and current interest in replacement with a mitral homograft or heterograft warrant a new look at the normal functional anatomy of the system. We conducted a detailed review of the anatomic structure of both the intact and excised mitral apparatus of porcine and human species. The following intact structural dimensions were measured: total annular length, anterior and posterior annular length. Excised measurements included: total annular length, anterior and posterior annular lengths, leaflet edge lengths, leaflet heights, and anterolateral and posteromedial commissural heights. Leaflet area was calculated from planimetric measurements. Chordal lengths were measured and distribution recorded. The majority of leaflet measurements were not statistically different between groups. For both groups, the measured annular length increased significantly upon valve excision. In both groups, the posterior leaflet area was significantly larger than the anterior leaflet area, and the area of each leaflet alone was significantly greater than the calculated orifice area. Chordal length was not significantly different between groups, however, distribution varied slightly with the ratio of origins to insertions being 8:1 (porcine) and 5:1 (human). The results are consistent with previous studies of the human mitral valve. This study showed little difference between human and porcine data, and the porcine valve was identified as an appropriate model for further investigation of the mitral valve system.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8000583 TI - Afterload reduction in chronic aortic regurgitation: going in the right direction? PMID- 8000584 TI - Effects of 12 months quinapril therapy in asymptomatic patients with chronic aortic regurgitation. AB - This study was performed to assess the effects of one year of ACE inhibition with quinapril on left ventricular performance and morphology in asymptomatic patients with chronic aortic regurgitation. Pre- and afterload reduction is known to have beneficial effects in patients with chronic aortic regurgitation. To date, no controlled study has been reported analyzing long term influence of ACE inhibitor treatment on asymptomatic patients with chronic aortic regurgitation. Twelve asymptomatic patients with isolated moderate to severe chronic aortic regurgitation, no coronary disease on coronary angiography and no previous vasodilator treatment were studied under control conditions and after three and 12 months of quinapril therapy (10-20 mg/day) using echocardiography and simultaneous right heart catheterization and radionuclide ventriculography at rest and during supine bicycle exercise. After one year quinapril therapy regurgitant fraction fell by 17% compared to control before therapy (p = 0.001), left ventricular enddiastolic volume at rest was reduced from 150 +/- 33 to 128 +/- 30 ml/m2 (p = 0.0003) and endsystolic volume decreased from 55 +/- 27 to 44 +/- 28 ml/m2 (p = 0.0005). Left ventricular ejection fraction at rest averaged 0.64 +/- 0.11 at control and increased after one year therapy to 0.67 +/- 0.11 (p = 0.05). With maximum exercise (100 W), ejection fraction failed to rise at control; after one year therapy with quinapril it increased to 0.70 +/- 0.15 (p = 0.019). Moreover, after one year quinapril therapy there was a significant reduction of 35% in left ventricular mass compared to control.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8000586 TI - Valvular heart disease: the influence of changing etiology on nosology. AB - The many changes in classification of cardiovascular disease during the twentieth century reflect changing etiology of diseases, clinical comprehension and technological advances. In particular, the etiology of valvular heart disease has changed dramatically in the last five decades. The significant reduction of acute rheumatic fever and its sequelae, and the recognition of non-rheumatic causes of valvular disease are responsible for the metamorphosis in the etiology of valvular disorders. Valvular heart disease can be classified as follows: 1) Heritable-congenital causes of valvular heart disease e.g., floppy mitral valve with mitral valve prolapse, bicuspid aortic valve, and the Marfan syndrome; 2) Inflammatory-immunologic causes such as rheumatic fever, acquired immune deficiency syndrome, endocardial proliferative disorders, and antiphospolipid syndrome; 3) Myocardial dysfunction-ischemic cardiomyopathy, dilated or hypertrophic cardiomyopathy-resulting in valvular heart disease; 4) Diseases and disorders of other organs as causes of valvular heart disease, e.g., chronic renal failure and carcinoid heart disease; 5) Valvular heart disease related to aging: calcific aortic stenosis and mitral annular calcification; 6) Valvular disease following interventions such as valvuloplasty, valve reconstructive surgery and valve replacement; and 7) Valvular disease related to drugs and physical agents, such as chronic ergotamine use, radiation therapy and trauma. In clinical practice the most common causes of mitral regurgitation are floppy mitral valve with mitral valve prolapse, ischemic heart disease, dilated cardiomyopathy and mitral annular calcification, while the most common cause of mitral stenosis is rheumatic fever. The most common causes of isolated aortic regurgitation are bicuspid aortic valve and floppy aortic valve, while the most common causes of isolated aortic stenosis are related to the bicuspid aortic valve and the development of calcific senile aortic stenosis. The most common causes of tricuspid regurgitation are dilated cardiomyopathy, ischemic cardiomyopathy, floppy tricuspid valve with tricuspid valve prolapse and infectious endocarditis. Combined mitral and tricuspid regurgitation occur with heritable connective tissue disorders, dilated or ischemic cardiomyopathy, while the most common cause of mitral stenosis plus aortic regurgitation is rheumatic fever. Statistics obtained from cardiac surgery and necropsy may underestimate the true incidence of certain valvular diseases by selection bias. This is particularly so with valvular disease associated with significant ventricular dysfunction, or in the elderly who may not be surgical candidates, or in cases where the valvular disease is not severe enough to require surgical intervention. Recent advances in hemodynamic and imaging technology allow clinicians to define valvular structure and function and to accurately classify valvular heart disease in clinical practice. PMID- 8000585 TI - Hemodynamic changes during dipyridamole stress in patients with aortic stenosis. AB - Dipyridamole is a potent vasodilator used in pharmacologic stress testing. Patients with severe aortic stenosis are not suitable for exercise, and are usually not subjected to testing with vasodilator substances. The aim of the present study was to investigate hemodynamic changes during dipyridamole stress test in patients with aortic stenosis and to see if these changes where reversible by theophylline, an aminophylline derivative. Ten patients with aortic stenosis underwent right and left heart catheterization. Simultaneous recordings of cardiac output, left ventricular and aortic pressures were performed at baseline, after intravenous dipyridamole infusion (0.56 mg/kg dissolved in 250 ml of saline given over four minutes), and after intravenous theophylline injection (115 mg). There was an increase in heart rate, stroke volume and flow, and a decrease in systolic and diastolic blood pressure and in systemic vascular resistance after dipyridamole infusion. Left ventricular stroke work index and pressure time per minute increased after dipyridamole infusion suggesting an increase in myocardial oxygen demand, but there was no significant change compared to baseline after theophylline administration. Less than one third of left ventricular work was due to the resistance of the aortic valve. The aortic valve area changed with changes in flow. It is concluded that cardiac output, left ventricular work and myocardial oxygen demand after dipyridamole infusion increased in patients with aortic stenosis. The systemic vascular resistance seems to be more important determinant of cardiac output than the aortic valve obstruction. The calculated valve area appears to be flow-dependent.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8000587 TI - Coronary artery bypass surgery and minor aortic stenosis--the need for tailored solutions. PMID- 8000588 TI - Long-term clinical outcome with small size Standard St Jude Medical valves implanted in the aortic position. AB - Records of 144 patients who received size 19 or 21 mm (Group A) aortic Standard St. Jude Medical (SSJM) prostheses were retrospectively reviewed and compared to 219 patients who received size 25 mm SSJM valves (Group B). Group A patients were older (70 +/- 9 years vs. 62 +/- 13 years) and had smaller body surface area (BSA) (1.65 m2 vs. 1.9 m2 p < 0.05). Operative mortality (5% vs. 2%) and postoperative unadjusted Doppler mean gradient (31 mmHg vs. 22 mmHg) were higher in Group A (p < 0.05). Total follow up was 1255 patient-years (450.6 Group A/804.4 Group B). There were no perivalvular leaks, valve thrombosis, or endocarditis in either group. Freedom from thromboembolism and anticoagulant related hemorrhage was 89% and 95% in Group A and 93% and 98% in Group B, respectively. The major causes of late death were older age and progressive cardiac disease. The five-year actuarial analysis revealed a survival rate of 74% in Group A and 83% in Group B (p < 0.05). Of those who were alive, more than 70% were in functional class I and II. These patients not only enjoy a complication free living but are able to perform daily routine activity despite being older. 19 mm and 21 mm SSJM aortic valve prostheses had higher transprosthetic gradient, but provided satisfactory performance in adult patients with a BSA of less than 1.7 m2. This valve can be used in the small aortic annulus with a valve size index of at least 12 mm/m2 as an alternative to an annular enlargement procedure. PMID- 8000589 TI - Long term clinical results with 19 mm or 21 mm standard aortic St. Jude Medical prosthesis. AB - Comparison of long term clinical results after aortic valve replacement with 19 mm or 21 mm vs. 23 mm or larger bileaflet prostheses has not yet been reported. Between December 1979 and September 1993, 80 consecutive patients who underwent isolated aortic valve replacement at Niigata University using a standard St. Jude Medical valve were assigned to small size group (19 mm and 21 mm, n = 34) or to large size group (23 mm or larger, n = 46). In the small size group, patient's age was older, body surface area smaller, female patients and calcified aortic stenosis were dominant (all p < 0.01). The left ventricular systolic dimension was shorter (p < 0.001), while the cardiothoracic ratio was similar to that of the large size group. All patients received warfarin treatment, and target thrombotest level was 15 to 25% (equivalent to INR 1.6 to 2.1). Actuarial survival rates including hospital death in the small size group (94% at fifth postoperative year) were comparable to those in the large size group. Cerebrovascular event occurred in two patients with the small size prosthesis (1.3%/pty) and three with larger prosthesis (0.9%/pty). Major hemorrhagic complication was not observed in either group. No significant difference was noticed in the proportion free from valve-related morbidity. In the patients with aortic stenosis (n = 41), the left ventricular posterior wall thickness decreased from 15 mm preoperatively to 11 mm late post surgery in both groups.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8000590 TI - Early experience with the Jyros bileaflet valve in the mitral position: high incidence of valve thrombosis. AB - The Jyros valve is a new bileaflet valve with the unusual feature that the hinge is expected to rotate continuously inside the housing. Nine isolated Jyros mitral prostheses were implanted from July to October 1993. All patients survived the surgical procedure and during the follow up underwent transthoracic (TTE) and transesophageal echocardiograms (TEE) for the evaluation of hinge rotation. Neither TTE nor TEE were able to show hinge rotation in any patient at any time. Five patients had prosthetic thrombosis. In the successfully treated with thrombolysis. In the remaining patient thrombolysis was contraindicated. Eight patients are alive; one died of gastro-intestinal bleeding a few months after discharge. The absence of hinge rotation may be the triggering mechanism of valve thrombosis although no explanted prostheses were available for examination. Further studies are necessary to understand the mechanism of valve thrombosis with the Jyros bileaflet prosthesis. PMID- 8000591 TI - Echocardiographic features of the normofunctional Labcor-Santiago pericardial bioprosthesis. AB - Echocardiography was performed in 94 patients with a total of 99 normally functioning Labcor-Santiago bioprostheses, 62 in the aortic and 37 in the mitral position. The following variables were measured: peak and mean transvalvular velocities, peak and mean instantaneous pressure gradients as calculated from the modified Bernoulli equation, pressure half-time, cardiac index, stroke volume and effective orifice area (using continuity and Hatle equations). Regurgitation patterns were sought by transthoracic echocardiography (all valves) and, for selected mitral bioprostheses, by transesophageal echocardiography. Calculated mean aortic pressure gradient ranged from six to 10 mmHg and calculated effective aortic orifice area increased with ring diameter, with means of 1.27 cm2 for the 19 mm valve and 2.58 cm2 for the 27 mm valve. For mitral bioprostheses, mean pressure gradient ranged from 3.0 to 4.5 mmHg and calculated effective orifice area from 2.27 to 2.73 cm2. Only central regurgitation was observed. The Labcor Santiago pericardial bioprostheses created little resistance to forward flow. In the small aortic root their hemodynamic performance was as good or better than that of other currently available devices. It is hoped that this new design will contribute increased in vivo mechanical durability. PMID- 8000592 TI - Comparison of structural valve failure among different 'models' of homograft valves. AB - Aortic homograft valves are accepted as excellent valve substitutes in the aortic position. Compared to stented bioprostheses, they are considered to have better hemodynamics and a zero or negligible thrombogenicity. Their perceived major single shortcoming is limited durability, but there is apparent broad variation within published data in this respect. Study of the relevant literature reveals important differences between procurement, sterilization and preservation of the individual series refuting any attempt at making a scientifically valid comparison of overall performances. Surgical method and patient selection are further sources of variation among reported long term results. Nevertheless, it appears that (a) cryopreservation produces results at least as good as those of other preservation methods, and (b) the worst results are those of series with the longest follow up. However, the good results with cryopreserved valves are reported in series with limited length of follow up. Because of the many variable factors associated with the use of homograft valves, a comprehensive set of definitions should be introduced, accepted and adhered to in reporting results. PMID- 8000593 TI - A database obtained from in vitro function testing of mechanical heart valves. AB - The in vitro function of the CarboMedics, Medtronic Hall, Omniscience, Starr Edwards, St. Jude and Sorin (formerly Shiley) Monostrut heart valves have been compared using a pulsatile flow model left heart and load system. A wide range of flows and heart rates were used. The above valves in all sizes and in both aortic and mitral positions were tested. Results for transvalvular pressure, regurgitation and effective orifice area are presented. The small size St. Jude valves showed the least transvalvular pressure and largest effective orifice area. For large valves, the least regurgitation was exhibited by the Starr Edwards valve. The data provides a reference for the range of normal performance that can be expected of mechanical prosthetic heart valves. PMID- 8000595 TI - Disc failure in a Bjork-Shiley mitral prosthesis. AB - The case of a 50-year-old man is presented who underwent reoperation for a malfunctioning Bjork-Shiley spherical valve which had been inserted 14 years previously. The patient made a satisfactory recovery after surgery. Examination of the explanted valve revealed that a segment of the pyrolytic carbon disc was missing. There was no evidence of embolization. PMID- 8000594 TI - Hydrodynamic performance of the Medtronic Freestyle Aortic Root Bioprosthesis. AB - The Freestyle Aortic Root Bioprosthesis is comprised of a porcine aortic root preserved in buffered 0.2% glutaraldehyde solution. It is fixed at a pressure sufficient to distend the aortic wall, but the leaflets are fixed with no transvalvular gradient. The bioprosthesis is treated with alpha-amino-oleic acid (AOA) to reduce the potential for leaflet calcification. In order to conduct in vitro performance studies, a simulated aorta test chamber was developed. The test chamber material formulation can be altered to produce a wide range of desired compliances, while maintaining repeatable dimensional specifications. The test chamber design also allows for performance testing simulating a variety of implant techniques. Both Freestyle and the stented control valves (Hancock Standard Model 242) were mounted within the simulated aortas for these studies. Steady state and pulsatile flow pressure drop studies demonstrated a significantly lower gradient across the Freestyle valve when compared to stented Hancock Standard controls. In addition, the smaller size (19,21,23 mm) Freestyle valves had superior EOA's compared to the Standard St. Jude bileaflet mechanical and Hancock modified orifice (MO) porcine valve designs. The regurgitant volumes were equivalent to the control (Hancock Standard model 242) valves when compared to the Freestyle valves with equivalent flow areas. Additional studies were conducted in order to determine the effects of sizing and configuration on hydrodynamic performance. These studies were performed in four configurations: total root, inclusion, partially scalloped (two sinuses) and fully scalloped valve. These studies demonstrated that both pressure drop and regurgitation are significantly affected by valve sizing and implant technique. Accelerated wear studies were performed on three of each size and six of the largest Freestyle valves. Stented Hancock Standard valves and non-AOA treated Freestyle valves were used as controls. Hydrodynamic performance tests were conducted at intervals throughout the study. No evidence was found to indicate a difference in wear or hydrodynamic performance between the AOA treated and untreated Freestyle valves. PMID- 8000596 TI - Fatal cerebral air embolism during open heart surgery caused by lung parenchyma to left atrial communication. AB - We present an unusual sequence of events leading to massive cerebral air embolism and death in a patient who underwent mitral valve re-replacement for failure of the previously inserted bioprosthetic valve. An iatrogenic communication was created inadvertently between the adherent lung parenchyma and the left atrium. It caused a massive influx of air from the lung into the left atrium and systemic circulation causing fatal cerebral embolization. Retroperfusion was not effective. PMID- 8000597 TI - Failure of Hancock pericardial bioprostheses. PMID- 8000598 TI - Utility of echocardiographic quantitation of valve morphology in balloon mitral valvotomy: a gap between expectations and reality? PMID- 8000599 TI - Acute outcome of percutaneous Inoue-balloon mitral commissurotomy. AB - This study examines the acute results and the potential impact, if any, of 16 clinical, echocardiographic, hemodynamic and balloon-related variables on the acute outcomes of Inoue-balloon percutaneous transvenous mitral commissurotomy (PTMC). Of 107 patients, PTMC was successfully completed in 105 (98%) without cardioembolism or death, and resulted in an increase in mitral valve area from 0.8 +/- 0.2 cm2 to 1.7 +/- 0.4 cm2 (p = 0.0001) as assessed echocardiographically. Optimal results defined as a valve area improvement of > or = 50% and/or a final valve area of > or = 1.5 cm2 without significant mitral regurgitation (> or = 2 grade increase in mitral regurgitation or a final regurgitation > or = 3+) was obtained in 96 patients (91%). Significant mitral regurgitation was observed in six patients. On univariate analysis, patients with suboptimal results were older (52 +/- 7 vs. 44 +/- 10 years, p = 0.037) and were likely to have the procedure performed during the learning phase (first 33 vs.. subsequent 72 patients, p = 0.007) than those with optimal results, and patients with resultant significant mitral regurgitation had more severe pre-existing mitral regurgitation compared with those without (1.4 +/- 0.5 vs. 0.7 +/- 0.7, p = 0.0098). However, there were no independent predictors of either acute outcome identified in multivariate analysis. We therefore conclude that although Inoue balloon PTMC is a safe and highly effective procedure with a low risk of creating severe mitral regurgitation, the acute outcomes cannot be accurately predicted. PMID- 8000600 TI - Long term follow up after percutaneous mitral commissurotomy with the Inoue balloon-incidence of restenosis. AB - The long term outcome of 300 consecutive patients following percutaneous mitral commissurotomy (PMC) with the Inoue balloon was analyzed with regard to the incidence of restenosis. There were 256 females and 44 males (mean age 44.4 +/- 9.9 years, range 18-69 years), 52 had previous surgical commissurotomy, 96 were in atrial fibrillation, and 16 had a history of embolism. PCM was carried out with a success rate of 84% (no significant mitral regurgitation and mitral valve area (MVA) > 1.5 cm2). Two hundred and seventy patients were available for clinical and serial echocardiographic studies at six months, 12 months and once a year thereafter (18 patients operated on for mitral regurgitation less than six months after PMC, three patients lost to follow up, nine patients refused to return). MVA increased with PMC from 1.18 cm2 +/- 0.3 to 2.0 +/- 0.3 cm2 and then decreased to 1.8 +/- 0.3 at a mean follow up of 24.0 +/- 13.5 months (range 6 55). Echocardiographic restenosis (RS) (MVA at follow up < 1.5 cm2 with a 50% loss of the initial gain) was found in 38 patients (14%). Twenty-five (66%) of them remained in NYHA class I or II. Restenosis free survival according to the Kaplan-Mayer curve was 93%, 86%, 77% and 73% at 12,24,36 and 55 months respectively. None of the 24 clinical, hemodynamic, echocardiographic or procedural variables used on the Cox proportional hazard regression analysis identified predictors of restenosis free survival. CONCLUSIONS: The overall incidence of echocardiographic restenosis post PMC is low (12.6%) in patients followed for a mean period of two years and often occurs without worsened clinical symptoms. It may be difficult to define clinical, echocardiographic or procedural factors as significant predictors of restenosis free survival. PMID- 8000601 TI - High intensity transcranial Doppler signals (hits) after prosthetic valve implantation. AB - High intensity transcranial Doppler signals (HITS), assumed to be caused by microemboli, have been reported to occur in many patients with mechanical heart valve prostheses. The aim of our study was to quantify these phenomena and to find possible differences. Furthermore, parameters which might influence the prevalence of HITS were investigated. Monitoring of both middle cerebral artery frequency shift spectra was carried out for 10 minutes in 100 patients having an aortic (n = 64) and (n = 5)/or (n = 31) mitral mechanical heart valve prosthesis. The spectra were off-line screened for HITS by ear. The findings were correlated with the degree of anticoagulation and with the time period since implantation. To examine if platelet aggregates would be the underlying cause, another HITS count was done for 10 minutes prior to and 40 minutes after i.v. injection of 250 mg aspirin (ASA) as well as after four days of 100 mg/day ASA orally in a group of seven patients. Prior to surgery, HITS were present in only one patient. Postoperatively, HITS were detected in 54 of 100 patients. There was no significant difference between left and right sides, no correlation with anticoagulation, and only a borderline correlation with the time interval since implantation. Sixty-six percent of the 50 patients monitored within the first three postoperative weeks had HITS as compared to only 42% in 50 subjects who were examined three months or later after surgery (p < 0.05). With regard to the number of HITS an inverse behaviour was observed.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8000602 TI - Diagnostic pitfall and the reporting of cerebrovascular events in patients with prosthetic heart valves. PMID- 8000603 TI - The place of thrombolysis in the management of cerebral embolism after heart valve replacement. PMID- 8000604 TI - The application of biological tissues in cardiac valve surgery. The history of the first two decades. PMID- 8000605 TI - Biology of cardiac overload. A review. PMID- 8000606 TI - The Medtronic Intact porcine bioprosthesis: clinical performance to eight years. AB - The Medtronic Intact porcine bioprosthesis was implanted in 274 patients, in 278 operations, between 1984 and 1992 inclusive. Of the total patient population, 171 patients had 175 aortic valve replacements (AVR), 75 had mitral valve replacement (MVR), two had tricuspid valve replacement and 26 had multiple valve replacement (MR). Concomitant procedures, primarily coronary artery bypass, was performed in 97 (34.9%). The follow up was 98.2% complete; total follow up was 758 patient years, mean 2.8 years. The early mortality was 6.5% (18 patients) and the late mortality 4.0% per patient-year (30 patients). Of the late deaths, 10 were valve related-thromboembolism (n = 2), anticoagulant-related hemorrhage (n = 1), prosthetic valve endocarditis (n = 4), non-structural dysfunction (n = 2), and structural valve deterioration (n = 1). Only one death occurred as a consequence of reoperation. The freedom from thromboembolism at six and eight years was overall 86 +/- 4%; major 96 +/- 1%; fatal 99 +/- 1%. The overall linearized rate of thromboembolism was 3.0% per patient-year. The freedom from anticoagulant related hemorrhage was 93 +/- 3%; non-structural dysfunction 87 +/- 9%; and structural valve deterioration 97 +/- 2% (AVR 97 +/- 2% at six and eight years, MVR 100% at six years). The freedom from SVD by age groups was- < or = 35 years 100%; 36-50 years 94 +/- 6%; 51-65 years 98 +/- 2%; and > or = 65 years 97 +/- 2% (p = NS). The freedom from valve-related mortality at six and eight years was 86 +/- 8%; residual morbidity 96 +/- 1%; and reoperation 91 +/- 3%. The Medtronic Intact, zero-pressure glutaraldehyde fixed prosthesis requires continued long term assessment to determine if the low incidence of structural valve deterioration is maintained. PMID- 8000607 TI - Early clinical and hemodynamic evaluation of the aortic intact porcine bioprosthesis. AB - Between October 1990 and June 1992, 89 patients underwent aortic valve replacement using the Intact porcine bioprosthesis. Their mean age (+/- SD) was 74.6 +/- 7.8 years (range 48 to 92). Seventy-five percent were in NYHA Class III IV, 79 (89%) had AS or AS/AI, 10 (11%) had had previous cardiac surgery and 25 (32%) had an EF < 0.50. Associated procedures included CABG 45 (51%), septal myectomy 13 (15%), annular enlargement eight (9%), LV aneurysmectomy one, ascending aortic replacement one, and arch replacement one. Hospital mortality was four (4.5%). Hemodynamics were assessed with 2D echo with Doppler at seven days, six weeks and 12 months, and compared with 130 standard Carpentier-Edwards (C-E) porcine bioprostheses. At follow up, two patients have 2/4 perivalvular AI. The transvalvular gradients for the Intact valve were as follows: 21 mm-16.9 +/- 7.4 mmHg; 23 mm-18.9 +/- 6.2 mmHg; 25 mm-17.1 +/- 5.4 mmHg; 27 mm-15.0 +/- 3.7 mmHg; and 29 mm-15.0 +/- 2.1 mmHg. When compared to the standard Carpentier Edwards porcine bioprostheses, the 21 mm Intact valve had the same gradient as the C-E prosthesis. However, the transvalvular gradients were slightly higher for the Intact valve for sizes 23-29 mm when compared to the corresponding C-E valve. The effective orifice area and effective orifice area index was no different between the two valves. Satisfactory hemodynamics are seen in the smaller prostheses when valves are matched for BSA and when aortic annular enlargement is performed when necessary. PMID- 8000608 TI - 10-year experience with the Biocor porcine bioprosthesis in the aortic position. AB - Six hundred and nineteen consecutive patients had aortic valve replacement between January 1983 and January 1993 with the zero pressure fixed Biocor porcine bioprosthesis. Mean age was 66.2 years (range 17-88 years). Male/female ratio was 416/203. Concomitant cardiac procedures, mainly coronary bypass surgery, were performed in 35% (214/619). Early mortality was 5.9% (37/619). Late mortality was 15.8% (92/582). Actuarial survival at 10 years was 60.0 +/- 4.9% and freedom from valve-related mortality was 97.6 +/- 0.8%. Total follow up was 2308 years. The follow up was 99.2% complete. Thromboembolic rate was 1.1%/pty (fatal 0.1%/pty, major 0.3%/pty and minor 0.6%/pty). The incidence of prosthetic valve endocarditis was 0.3%/pty (fatal 0.1%/pty). Freedom from reoperation due to structural valve deterioration, non-structural dysfunction and prosthetic valve endocarditis was 78.1 +/- 10.7%, 98.5 +/- 0.6% and 97.6 +/- 0.9%, respectively. The occurrence of structural valve deterioration varied considerably between age groups. In patients below 50 years of age the actuarial freedom from structural valve deterioration was 52.4 +/- 22.0%, while it was 96.2 +/- 1.1% for those between 71 and 80 years. At the 10-year follow up all patients had improved clinically. Preoperatively, 75% of the patients were in NYHA classes III or IV compared to 8% at the 10-year follow up. We conclude, that the Biocor bioprosthesis has a low rate of complications in terms of thromboembolism, anticoagulant-related bleeding, prosthetic valve endocarditis and valve-related mortality as compared to mechanical valves and also to other bioprostheses. The durability of the Biocor bioprosthesis has increased slightly compared to that reported with other, earlier models when inserted in patients above 50 years of age. PMID- 8000609 TI - Hemodynamic assessment of the stentless Toronto SPV bioprosthesis by echocardiography. AB - Since March 1993 the Toronto SPVTM bioprosthesis has been implanted in 100 patients. Our prospective study evaluated the echocardiographic valve characteristics and the influence of the echocardiographic assessment on surgical technique. Transesophageal echocardiography (TEE) was applied before and during surgery, and transthoracic echocardiography (TTE) postoperatively. The average valve size implanted was 26.5 mm. Follow up was complete in 74 patients at six months and in 38 patients at one year. Pre-cardiopulmonary bypass (CPB) TEE valve sizing was accurate by +/- 1 mm in 81 patients as compared to mechanical sizing. Post-CPB valve closure was concentric in 99 patients. Minimal aortic incompetence was present in seven patients at one week, in two patients at six months and in one patient at one year. Mean pressure gradients ranged from 7.7 to 11.1 mmHg postoperatively. Overall mortality was 4%. One patient with non-structural dysfunction and another with endocarditis at one year postoperatively were reoperated successfully. At follow up there was a significant decrease in transvalvular pressure gradients and an increase in valve orifice areas. In 32 patients a decrease in left ventricular posterior wall (LVPW) hypertrophy was found (p < 0.001). There was a decrease in tissue depth and recurrence of the dynamic movement of the aortic root. It is concluded that TEE valve sizing is reliable for early valve selection. Valve incompetence is not a clinically relevant issue using the oversizing technique. Improved hemodynamics at follow up can be explained by remodeling of the aortic root and by a decrease in left ventricular hypertrophy. The excellent hemodynamic profile, resembling native aortic valve function, is impressive and has to be confirmed by long term evaluation. PMID- 8000610 TI - Total energy loss in prosthetic valves. PMID- 8000611 TI - Hydrodynamic performance of Carbomedics valves in double valve replacement. AB - Most patients undergoing double valve replacements have reduced myocardial capacity. However, little is known about the influence of valve sizes on myocardial energy consumption in double valve replacement. This study was designed to supply hydrodynamic data for the proper selection of sizes in double valve replacement. A mock loop system was used to measure the energy consumption of CarboMedics valves at conditions resembling rest (5 L/min) and moderate exercise (9 L/min). All combinations of aortic valves size #21 to #27 with mitral prosthesis sizes #25 to #29 were tested separately. Larger size aortic prostheses revealed remarkably less energy consumption up to size #27. Under high flow (9 L/min) this effect was more pronounced. In contrast, mitral valve prosthesis sizes #25 to #29 had similar hydrodynamic data. At low flow conditions (5 L/min) no significant benefit was found with the use of a larger mitral valve. Only a reduction of less than 10 percent of total energy consumption could be achieved with the use of a mitral valve larger than #25 at 9 L/min flow. In conclusion there is no hydrodynamic reason for using a valve larger than #25 in the mitral position for patients who exercise moderately. Continuous reduction of cardiac work can be expected with the use of the largest possible aortic prosthesis up to size #27 at rest and at moderate exercise. PMID- 8000612 TI - In vitro fluid dynamic evaluation of the Carbomedics bileaflet heart valve prosthesis in the aortic and mitral positions. AB - Since the introduction of bileaflet heart valve prostheses their clinical use has continued to escalate. The first of this valve type was the Standard St. Jude Medical (SSJM) prosthetic heart valve in 1977. The Carbomedics prosthetic heart valve (CPHV), introduced in the late 1980s, was intended to improve on the design of the SSJM bileaflet valve. The design changes in the CPHV valve, relative to the SSJM valve, may have the potential to affect its flow fields. This study, using flow visualization laser Doppler velocity measurements and color Doppler flow mapping, was intended to evaluate how these changes affect the flow fields in the near vicinity of the CPHV valve. The study was conducted in an in vitro pulse duplicator system. In the flow visualization study, the flow fields observed with the CPHV valve were quantitatively similar to those seen with the SSJM valve. Centralized jet-like flows with flow separation/stagnation were observed in the illuminated planes. The jet-like flows from the two lateral orifices were broader than that observed from the central orifice for both the CPHV and the SSJM valves. This fact implied that the major part of the volumetric flow was through the two lateral orifices, rather than the central orifice. In the laser Doppler velocity measurements, it was found that the flow field downstream of the SSJM valve was slightly more evenly distributed than that with the CPHV valve. In addition, the extent of the flow separation regions with the CPHV valve were slightly larger than with the SSJM valve. The slight differences in velocity profiles between the SSJM and the CPHV valves were due to the differences in leaflet opening angle. However, the levels of flow turbulence with the CPHV and the SSJM valves were found to be of the same order of magnitude. The results of the flow visualization and LDA velocity and turbulence measurements obtained in the study indicate that the differences in flow fields in the immediate vicinity of the CPHV valve relative to the SSJM valve are insignificant. PMID- 8000613 TI - Dynamic in vitro calcification of porcine aortic valves. AB - Previous work in our laboratory has demonstrated a simple, dynamic in vitro calcification method for studying bovine pericardial heart valves. The calcification produced closely resembled that found in clinical explant valves. The current study extends this technique to the porcine aortic bioprosthesis. Five Carpentier-Edwards porcine aortic bioprostheses were calcified in vitro in a modified wear tester. All valves calcified to a similar degree as bovine pericardial valves. Calcification predominated on the ribbed tissue structures near the commissures on the outflow surfaces. The same calcification pattern was seen in clinical explant valves. A number of anti-calcification modifications of porcine aortic valves were also investigated. These had all previously inhibited calcification of bovine pericardium in a rat subdermal implant model but had failed to reduce calcification in whole pericardial valves calcified in vitro under dynamic conditions. The modified porcine valves produced similar results: no modification achieved reduction of calcification on exposure to the functional valve calcification model. The dynamic in vitro calcification test has been shown to be useful for the study of both main types of bioprostheses, bovine pericardial and porcine aortic valves, and for the assessment of alterations to these biomaterials. PMID- 8000614 TI - Disappearing cardiac masses--the importance of intraoperative transesophageal echocardiography. AB - A 25-year-old man presented with sudden onset right-sided hemiplegia. Transthoracic and transesophageal echocardiograms demonstrated a mobile mass attached to the anterior mitral leaflet. The mass was, however, not found at operation. PMID- 8000615 TI - Cicatricial changes in a Ionescu-Shiley bioprosthesis. AB - The mitral Ionescu-Shiley standard-profile prosthesis of a 53-year-old woman who had it placed 12 years previously is described. The observed cicatricial retraction of one of the bioprosthesis' cusps is unusual, and it contributed to the bioprosthetic dysfunction which necessitated this valve's replacement. PMID- 8000616 TI - Valvular heart disease: the influence of changing etiology on nosology. PMID- 8000618 TI - Principles underlying the use of Holter monitoring to define the efficacy of antiarrhythmic drugs. PMID- 8000617 TI - Serial electrophysiologic-pharmacologic studies for the control of ventricular arrhythmias. PMID- 8000619 TI - Interpretation of the results of the Electrophysiologic Study Versus Electrocardiographic Monitoring (ESVEM) study: programmed ventricular stimulation advocates view. PMID- 8000621 TI - Interpretation of the results of the Electrophysiologic Study Versus Electrocardiographic Monitoring (ESVEM) study: impact on algorithm for drug selection. PMID- 8000620 TI - Interpretation of the results of the Electrophysiologic Study Versus Electrocardiographic Monitoring (ESVEM) study: electrocardiographic monitoring advocates' view. PMID- 8000622 TI - Cigarette smoking and the age at onset of a first non-fatal myocardial infarction. AB - BACKGROUND: Smoking is a major risk factor for coronary heart disease. Discontinuance of smoking is associated with a reduction in the risk of coronary disease; this risk approaches the level among non-smokers after stopping smoking for periods ranging from 6 months to several years. We analyzed pertinent prospectively accumulated data from our multicenter postinfarction studies to gain further insight into the complex relationship between cigarette smoking and the premature occurrence of a first myocardial infarction. METHODS: Retrospective analysis of the relationship between the number of cigarettes smoked and the age at onset of patients experiencing their first non-fatal myocardial infarction was investigated in 2445 patients. The intensity of smoking was quantitated in terms of the average number of packs per day smoked during adult years, subcategorized in increments of a half-pack per day up to more than two packs per day. Ex smokers were identified if they had stopped smoking 1 month before their index infarction. Analysis of variance was used to adjust for the effects of relevant confounding risk factors. RESULTS: The adjusted age for first non-fatal infarction progressively declined with increasing smoking exposure, with an average age reduction of 8.7 years (95% confidence interval; 7.2, 10.2) in those smoking more than two packs per day compared with non-smokers. The graded effect was somewhat more marked in women than in men. The number of cigarettes smoked before infarction had no effect on the severity of the acute infarction or on mortality from cardiac causes during more than 2-year post-hospital follow-up. Those who stopped smoking 1 month or longer before the infarction were significantly older at the time of first infarction than active smokers in all smoking categories. CONCLUSION: This study provides strong evidence that active smoking is associated with an earlier age at onset of first infarctions, with a striking inverse dose-response effect. Stopping smoking appears to reduce the premature occurrence of coronary events. PMID- 8000623 TI - Chylomicrons or their remnants penetrate rabbit thoracic aorta as efficiently as do smaller macromolecules, including low-density lipoprotein, high-density lipoprotein, and albumin. AB - BACKGROUND: The aortic accumulation of chylomicrons, low-density lipoprotein (LDL), high-density lipoprotein (HDL) and albumin were compared in normal New Zealand White rabbits. METHODS: Lipoproteins and albumin were labelled with radioiodinated tyramine cellobiose (TC) to avoid potential oxidative modification of lipoproteins and as a marker of intracellular degradation. In preliminary experiments it was established that TC labelling did not alter the kinetic properties of lipoproteins in vivo. Importantly, radiolabelled apolipoproteins did not transfer significantly between plasma lipoproteins. Therefore, aortic radioactivity following infusion of TC-radiolabelled lipoproteins was considered to be indicative of lipoprotein accumulation. RESULTS: In conscious rabbits, net aortic accumulation of chylomicrons or their remnants was similar to those of LDL, HDL and albumin up to 2 h after infusion, despite rapid clearance from plasma. When accumulation was calculated on the basis of mean arterial exposure to allow for the differences in plasma clearance, the accumulation of aortic chylomicrons/remnants was substantially greater than that of LDL, HDL or albumin. Qualitatively similar results were obtained in rabbits that were functionally eviscerated to slow clearance of chylomicron remnants. Chylomicrons/remnants did not appear to efflux from aortic tissue as rapidly as did LDL or other plasma lipoproteins. Autoradiographic analysis showed that the primary site of lipoprotein accumulation was within medial smooth muscle cells. CONCLUSION: Our data demonstrate that chylomicrons/remnants accumulate in arterial blood vessels more rapidly than does LDL, suggesting that dietary lipoproteins may be directly involved in the pathogenesis of atherosclerosis. PMID- 8000624 TI - Primary coronary angioplasty versus intravenous streptokinase in acute myocardial infarction: differences in outcome during a mean follow-up of 18 months. AB - BACKGROUND: Intravenous streptokinase and primary coronary angioplasty are both considered to be effective treatment strategies for patients with acute myocardial infarction. Although primary coronary angioplasty is associated with a high patency rate and a well-preserved left ventricular function, it is not known whether it results in a more favorable clinical outcome in randomized comparisons. METHODS: Clinical data were obtained after a mean follow-up of 18 months (range 6-36 months) after random allocation of 301 patients either to intravenous streptokinase (n = 149) or to primary angioplasty (n = 152). The primary endpoint includes death from cardiac causes and non-fatal reinfarction. The secondary endpoint is a weighted unsatisfactory outcome, one that includes death, stroke, heart failure, shock, ejection fraction lower than 30%, reinfarction, reocclusion and bleeding complications. The need for revascularization procedures was recorded. RESULTS: The relative risk of death from cardiac causes and non-fatal reinfarction in the streptokinase group was 6.1 (95% confidence interval 2.9-12.7) compared with the angioplasty group. There was a lower weighted unsatisfactory outcome score of 0.13 +/- 0.29 in patients randomly assigned to angioplasty compared with 0.34 +/- 0.33 in patients randomly assigned to streptokinase (P < 0.001). Coronary angioplasty or coronary artery bypass grafting, or both, were performed more often in the streptokinase group, with a relative risk of 2.1 compared with patients randomly assigned to angioplasty (95% confidence interval 1.5-3.2). CONCLUSION: Clinical outcome in patients with acute myocardial infarction after a mean follow-up of 18 months was more favorable in patients randomly assigned to primary angioplasty compared with those receiving intravenous streptokinase. PMID- 8000625 TI - Coronary artery bypass grafting early after acute myocardial infarction in patients initially treated with thrombolytic therapy or coronary angioplasty. AB - BACKGROUND: Treatment of patients with acute myocardial infarction should aim to restore blood flow in the infarct-related artery as soon as possible. Thrombolytic therapy has recently been compared with direct angioplasty; however, these interventions may not be sufficient, and coronary artery bypass grafting (CABG) may be necessary. METHODS: In a series of 301 patients with acute myocardial infarction, randomly assigned either to receive intravenous streptokinase (n = 149) or to undergo percutaneous transluminal coronary angioplasty (PTCA; n = 152), 31 patients (aged 61 +/- 10 years; 27 men, four women) underwent CABG within 6 weeks of acute myocardial infarction. RESULTS: Twelve patients (nine in the PTCA group and three in the streptokinase group) underwent surgery within 48 h of the onset of symptoms. Bypass surgery was performed in the streptokinase group on failure of thrombolytic therapy (n = 2), recurrent ischemia (n = 4), or postinfarct angina (n = 9). In the PTCA group, CABG was performed for left main stenosis (n = 6), failed PTCA (n = 3), recurrent ischemia (n = 2), or postinfarct angina (n = 5). An intra-aortic balloon pump (IABP) was required in 15 patients (five streptokinase and 10 PTCA). Major complications after CABG were more common among patients who underwent surgery within 48 h than those after 48 h (eight in 12 patients versus four in 19, respectively). After 17.0 +/- 8.6 months (range 3-33 months), two patients had died; one of end-stage heart failure after 3 months, and one of a stroke after 16 months (both were in the PTCA group and one had undergone surgery within 48 h). One patient suffered a reinfarction after 11 months and one a non-fatal stroke after 1 month (both underwent CABG within 48 h). The left ventricular ejection fraction did not differ between the groups (43 +/- 15% for the 'early' group and 42 +/- 11% for the 'late' group). CONCLUSION: CABG can be performed safely and effectively after initial treatment with direct angioplasty or thrombolytic therapy after acute myocardial infarction. If it is performed within 48 h of onset of symptoms, (in-hospital) morbidity is higher, without affecting mortality or left ventricular function. PMID- 8000626 TI - Toward achieving optimal reperfusion: revisiting thrombolysis. PMID- 8000627 TI - Bibliography of the current world literature. PMID- 8000628 TI - Transperitoneal absorption of thermocautery-induced carbon monoxide formation during laparoscopic cholecystectomy. AB - Carbon dioxide pneumoperitoneum (PP) during laparoscopic cholecystectomy (LC) causes hypercapnia and acidemia. Thermocautery carbon monoxide formation during LC was studied in 15 patients. CO samples were read by electrochemical sensor as parts per million (ppm) and obtained intraperitoneally at PP, gallbladder takedown (GBTD), and exhalation. In blood, CO was measured by spectrophotometry as percentage of carboxyhemoglobin (HbCO) during anesthesia induction, at end of PP, at GBTD, and in the recovery room. Heart rate, mean arterial pressure, oxygen saturation, and end-tidal CO2 were followed prospectively. Data were analyzed by analysis of variance and Student's t test. In 35 min, thermocautery increased intraperitoneal CO from 4.7 +/- 3.8 ppm at baseline to 326 +/- 360 ppm at GBTD (p < 0.004). HbCO increased from PP to GBTD (0.7 +/- 0.6 vs. 1.2 +/- 0.7%; p < 0.01). Thermocautery produces high levels of CO intraperitoneally, which are absorbed into the circulation. Exposure time is short, which may explain the lack of hemodynamic and oxygenation changes. PMID- 8000629 TI - An experimental model for laparoscopic common bile duct exploration. AB - The development of an effective and reliable technique for laparoscopic common bile duct exploration has been limited by the technical difficulty of the procedure and the lack of a suitable animal model with a bile duct diameter large enough to accommodate the fiberoptic choledochoscope and other instruments used for stone extraction. Short-term bile duct ligation in the dog provides a simple and reproducible animal model that enables the surgeon to gain experience with laparoscopic common bile duct exploration in a laboratory setting. This model will enable the surgeon to develop the technical skills necessary to perform laparoscopic common bile duct exploration. In addition, the model may facilitate the development and refinement of new techniques and instruments that will facilitate laparoscopic common bile duct exploration in the clinical setting. PMID- 8000630 TI - Intramuscular diclofenac sodium for postoperative analgesia after laparoscopic cholecystectomy: a randomised, controlled trial. AB - Laparoscopic cholecystectomy is the surgical treatment of choice for symptomatic gallstones. Nonsteroidal antiinflammatory drugs offer effective analgesia, avoiding the central side effects of opiate drugs. To assess intramuscular diclofenac sodium (Voltarol; Ciba-Geigy) after laparoscopic cholecystectomy, 55 consecutive patients (41 female; 14 male; mean age: 50 years) were randomised to receive either diclofenac or placebo in double-blind fashion. Six patients were withdrawn from study (three conversions to open cholecystectomy; three incomplete documentation). Pain scores were assessed at 4, 24, and 48 h using a linear analogue scale; opiate consumption and time to first oral fluid and food were recorded. In 26 patients receiving diclofenac, median scores at 4 h were 1.6 (range 0-7.6) as compared with 4.1 (range 0-7.6) in 23 control patients (p = 0.05, 95% confidence limits 3.2, 0; Mann-Whitney U test). Nausea scores, return to diet, and time to discharge did not differ significantly between the groups. Intramuscular diclofenac significantly reduces early postoperative pain after laparoscopic cholecystectomy and is worthy of consideration if the procedure were ever undertaken as day case surgery. PMID- 8000631 TI - Indications for laparoscopic formation of intestinal stomas. AB - A laparoscopic technique for formation of intestinal stomas is described and reported in four cases. The procedure has a role where difficulties with trephine stoma formation are anticipated, where simultaneous laparoscopic procedures are performed, and where accurate assessment of the extent of intra-abdominal malignancy is indicated. PMID- 8000632 TI - Laparoscopic right hemicolectomy in left lateral decubitus position. AB - The laparoscopic surgeon does not have the luxury of manually retracting small bowel loops during right colonic mobilization and transection. Intraoperative rotation of the table aids gravity-produced displacement of small-bowel loops but is limited because extreme rotation endangers the patient's positional stability. By placing the patient in left lateral decubitus position before sterile draping, gravity-aided displacement of small-bowel loops can be maximized, facilitating safe and swift laparoscopic right colonic dissection and transection. Unlike the supine position, the left lateral decubitus position also permits transoperative colonoscopy, which may be needed to aid laparoscopic identification of nonpalpable intraluminal colonic lesions. Experience with four patients is reported. PMID- 8000633 TI - Can pulse oximetry and end-tidal capnography reflect arterial oxygenation and carbon dioxide elimination during laparoscopic cholecystectomy? AB - An investigation was carried out on 13 ASA class 1 or 2 adult patients undergoing laparoscopic cholecystectomy. Throughout laparoscopy, the end-tidal PCO2 was continuously monitored by capnography and the arterial hemoglobin oxygen saturation by pulse oximetry. Also, repeated measurements of arterial blood gases were done. Ventilation was controlled using an inspired oxygen concentration of 33% and tidal volume of 10 to 15 ml/kg at a rate of 10-14/min. The report showed that both the mean end-tidal PCO2 and arterial PCO2 progressively increased following carbon dioxide insufflation, to reach a maximal value after 30 min, with no significant change in the arterial-alveolar PCO2 gradient. Also, the arterial PO2 significantly decreased, and the hemoglobin oxygen saturation was always above 98% whether monitored by arterial blood gas analysis or by pulse oximetry. The results suggest that end-tidal capnography and pulse oximetry can be used as noninvasive techniques for monitoring arterial oxygenation and carbon dioxide elimination during laparoscopic cholecystectomy. PMID- 8000634 TI - Rectal prolapse. AB - Marlex rectopexy is a popular and effective procedure for the repair of rectal prolapse. Heretofore, this operation has required a generous laparotomy. As videolaparoscopy provides superior pelvic exposure, performing a modified Ripstein procedure was a logical progression of minimally invasive surgery. Experience with the first sutured Marlex rectopexy suggested the need for a simple fixation device to secure the mesh to the sacrum. A commercially available orthopedic staple allows quick and secure fixation. Five cases of laparoscopic Marlex rectopexy provide our initial clinical experience. The LCR staple has reduced operating times by up to 1 h. Results in these cases show virtual complete repair of the prolapse, minimal postoperative analgesic requirements, and no postoperative incontinence. There was one postoperative complication requiring reoperation. There were no deaths. Laparoscopic stapled Marlex rectopexy is a promising modality for the treatment of procidentia. PMID- 8000635 TI - Tap needle for laparoscopic surgery: a safe and easy technique for holding tissues. AB - To achieve and maintain a wide operative field during laparoscopic surgery, we developed a "tap needle" that can penetrate the skin into the peritoneal or pleural cavities and can be used to pick up threads introduced into the cavities to elevate tissues or organs. The characteristics of the tap needle and method of use are reported herein. PMID- 8000636 TI - Extraperitoneal endoscopic access to the pelvic regions via a suprapubic route. AB - Transperitoneal endoscopic access for operations on the extraperitoneal pelvic regions exposes the patient to greater complications compared with the traditional surgical technique and increases the risk of operative morbidity. Access can be gained to the pelvic extraperitoneal space by suprapubic puncture, positioning the needle by insufflation in a midline position 1 cm above the pubis between the linea alba and the vesicoumbilical fibrous septum. PMID- 8000637 TI - Cholecystectomy and hernioplasty during the same laparoscopic procedure. AB - Cholelithiasis and inguinal or femoral hernia usually coexist in the same patient. The simultaneous laparoscopic approach to these diseases benefits the patients, who avoid two separate admissions to the hospital, two operations, and twice the cost, recuperation, and potential morbidity and mortality. The authors describe a technique that facilitates cholecystectomy and hernioplasty during the same laparoscopic approach, thus avoiding the use of two separate procedures. The results of this procedure in the first six patients were excellent. PMID- 8000639 TI - Laparoscopic cholecystectomy from fundus downward. AB - Laparoscopic cholecystectomy from fundus downward (LCFD) is desirable when exposure of the cystic duct is difficult and hazardous. First the cystic duct and artery are exposed and clipped, and the artery is divided. Then removal of the gallbladder is started from fundus downward. After the gallbladder is dissected from the liver bed, the cystic duct is double clipped and divided. This approach affords better visualization of the cystic duct and common duct with less chance of common duct injury. Twenty-eight LCFDs were performed without complications, immediate or late. LCFD appears to be a safe procedure and does not compromise the retrograde method. PMID- 8000638 TI - Laparoscopic cholecystcholangiography in a patient with biliary atresia. AB - A 24-day-old female newborn with persistent jaundice and acholic stool was diagnosed by laparoscopic cholecystcholangiogram. A catheter was inserted through a small incision at the fundus of the gallbladder. With definitive diagnosis of biliary atresia, laparotomy was performed, and Kasai's operation was carried out successfully. PMID- 8000640 TI - Recurrent hemobilia after laparoscopic cholecystectomy. AB - Hemobilia occurred 1 month after a laparoscopic cholecystectomy, the result of an aneurysm of the right branch of the hepatic artery. The aneurysm was treated by selective arterial embolization. Recurrent bleeding 28 days later was treated by embolization with platinum coils. The mechanism of occurrence of the aneurysm and its treatment are discussed. PMID- 8000642 TI - Laparoscopy and coloscopy-assisted resection of polypoid colonic tumor. PMID- 8000641 TI - Preoperative diagnosis of Meckel's diverticulum by pertechnetate scan and laparoscopic resection. AB - Acute lower gastrointestinal hemorrhage in a 17-year-old boy was caused by a Meckel's diverticulum 1 day after ingestion of 500 mg acetylsalicylic acid. After conservative treatment of the bleeding, the diverticulum was diagnosed in the free interval by technetium pertechnetate scintigraphy, which showed an accumulation in the right lower quadrant simultaneously with the accumulation in the gastric mucosa. Elective explorative laparoscopy confirmed the diverticulum, and the resection was performed by laparoscopic means. Histology showed gastric type mucosa in the diverticulum. The treatment of choice for Meckel's diverticulum, when it is diagnosed preoperatively or during laparoscopy, is laparoscopic resection. PMID- 8000643 TI - Laparoscopic excision of a patent urachus. AB - We report the case of a patent urachus presenting as an umbilical discharge. The urachus was visualised laparoscopically, divided at either extremity, and successfully removed with subsequent abrogation of symptoms. PMID- 8000644 TI - Hernia '93: advances or controversies--an international perspective. Indianapolis, May 24-27, 1993. Abstracts. PMID- 8000645 TI - Assessment of five-year experience with abdominal organ cluster transplantation. AB - BACKGROUND: Upper abdominal exenteration (resection of the liver, stomach, spleen, pancreaticoduodenal complex, and part of the colon) for the treatment of otherwise unresectable tumors is one of the more radical operations in oncology. This study was done to analyze retrospectively a five-year experience with exenteration in 57 patients treated with variations of resectional and transplant reconstructive techniques. STUDY DESIGN: Sixty-one transplantations were performed upon 57 patients. Three different organ replacement techniques were used: liver-pancreas-duodenum en bloc (original procedure), liver only (modified procedure), and liver plus pancreatic islets. The diagnoses were cholangiocarcinoma (20 patients), hepatocellular carcinoma (12 patients), endocrine neoplasms (14 patients), sarcoma (six patients), and adenocarcinoma of the pancreas (two patients), colon (two patients), or gallbladder (one patient). Analyses of survival and tumor recurrence were stratified by procedure variations, type and extent of tumor, and immunosuppressive regimen. RESULTS: The three month and one, two, three, and five year actuarial patient survival rates were 82, 56, 38, 33, and 30 percent, respectively. Eighteen (31.5 percent) of the 57 patients are alive after 425 15 (standard deviation) months (range of 17 to 61 months) and 12 patients are tumor free. The actuarial survival rates stratified by transplantation procedure, immunosuppression, and tumor diagnosis and extent showed no statistically significant differences beyond the three different transplantation groups. Endocrine tumors had a better three-year survival rate (64 percent) than sarcoma (44 percent), hepatocellular carcinoma (25 percent), cholangiocarcinoma (20 percent), and the other adenocarcinomas (20 percent). Twenty-three patients (40 percent) died as a result of tumor recurrence. Patients with combined factors of no lymph node involvement, absence of vascular invasion, and metastases to the liver only (11 patients) had the lowest incidence of recurrence (27 compared to 73.5 percent, p = 0.006). CONCLUSIONS: Patients with unresectable endocrine neoplasms, fibrolamellar hepatocellular carcinoma, and selected cholangiocarcinoma confined to the liver can benefit from this radical operative approach. Patients with sarcoma can achieve long survival periods but have a high recurrence rate. PMID- 8000646 TI - Interposed jejunal segment with nipple valve to prevent reflux in biliary reconstruction. AB - BACKGROUND: Resection is the accepted management of a choledochal cyst. However, the debate continues regarding the optimal method of biliary reconstruction. The Roux-en-Y limb is used most frequently, but concerns have been raised about this method due to associated peptic ulcer disease, cholangitis, and poor growth. A method of reconstruction using an interposed segment of jejunum with a nipple valve placed between the common bile duct and the duodenum has been proposed. STUDY DESIGN: We have reviewed a series of 12 children requiring biliary reconstruction for choledochal cyst (11 children) and biliary stricture (one child). All had reconstruction with a nipple valve, and ten had an interposed segment of jejunum. RESULTS: All of the children are alive and have had follow-up evaluation from six months to 8.5 years (median of three years). Sequential examinations with ultrasound and biliary excretion scans have shown no evidence of obstruction, and liver function tests have remained normal. Three children have had cholangitis. One child had a brief episode in the perioperative period. The second child had cholangitis 16 months postoperatively, and the third child had multiple episodes of cholangitis. These latter two children were unique. One had Alonso-Lej type IV choledochal cyst with intrahepatic dilatation, which persisted after reconstruction. The other had a prior diversion with a Roux-en-Y limb from the gallbladder after resection of a choledochal cyst and had multiple episodes of cholangitis before reconstruction. These episodes are now controlled with chronic antibiotic suppression. Postoperative complications were limited to two episodes of obstruction of the small bowel requiring lysis of adhesions. No child has had peptic ulcer disease. These children have grown well after reconstruction, except for three with multiple anomalies or chronic pancreatitis. CONCLUSIONS: Biliary reconstruction with a jejunal interposition containing a nipple valve can be performed safely with a low incidence of complications. It offers a more physiologic method of reconstruction and a low incidence of postoperative cholangitis. PMID- 8000647 TI - Venovenous bypass using inferior mesenteric vein for portal decompression during orthotopic hepatic transplantation. PMID- 8000648 TI - An analysis of the problem of biliary injury during laparoscopic cholecystectomy. PMID- 8000649 TI - Technical aspects of minicholecystectomy. PMID- 8000650 TI - Prognosis of patients with bilateral carcinoma of the breast. PMID- 8000651 TI - Serosurvey of human immunodeficiency virus, hepatitis B virus, and hepatitis C virus infection among hospital-based surgeons. Serosurvey Study Group. AB - BACKGROUND: Because occupational blood contact places health-care workers at risk for infection with bloodborne pathogens, we wanted to estimate the prevalence of infection with human immunodeficiency virus (HIV), hepatitis B virus (HBV), and hepatitis C virus (HCV) among hospital-based surgeons and correlate the results with occupational and nonoccupational risk factors. STUDY DESIGN: All surgeons in training or in practice in general surgery, obstetrics and gynecology, or orthopedics at 21 hospitals in moderate to high AIDS incidence areas were eligible to participate in a voluntary, anonymous serosurvey. Serum samples were tested for HIV antibody, for HCV antibody, and for markers of HBV infection: hepatitis B surface antigen, total antibody to hepatitis B core antigen, and antibody to hepatitis B surface antigen. RESULTS: Of 2,887 eligible surgeons, 770 (27 percent) participated in the study. One of 740 surgeons not reporting nonoccupational risk factors was HIV seropositive (0.14 percent, upper limit 95 percent confidence interval [CI] equals 0.64 percent). None of 20 participants reporting nonoccupational HIV risk factors and none of ten not responding to the question on nonoccupational risk factors were HIV positive. Of 129 (17 percent) participants with past or current HBV infection, three (0.4 percent) had chronic HBV infection; all were negative for hepatitis B e antigen. Risk factors for HBV infection included not receiving hepatitis B vaccine (odds ratio [OR] 14.7, 95 percent CI 8.3 to 26.0) and practicing surgery at least ten years (OR 2.2, 95 percent CI 1.3 to 3.8). Seven (0.9 percent) participants had anti-HCV. CONCLUSIONS: Although not necessarily generalizable to all surgeons in moderate to high AIDS incidence areas, these results do not indicate a high rate of previously undetected HIV infection among surgeons who trained or practiced in these areas, or both. Hepatitis B virus posed the highest risk of infection with a bloodborne pathogen, followed by HCV and HIV. PMID- 8000652 TI - Oxidized glutathione as a marker of ischemia reperfusion associated with single lung transplantation. AB - BACKGROUND: Previous data have shown that glutathione (GSH), an endogenous antioxidant, is converted to its oxidized form (GSSG) after oxidative ischemia reperfusion events. As GSSG is toxic to cells and is extruded through an active mechanism dependent on intracellular GSSG levels, substance appears in plasma. STUDY DESIGN: Single lung transplantation was performed upon 18 puppies, 3 to 5 kg, with a two hour ischemic time for the donor lung before reimplantation. Recipient animal plasma was obtained after anesthesia induction, pulmonary artery ligation, recipient pneumonectomy, reestablishment of blood flow to the donor lung, completion of transplant, and one, two, and three hours postoperatively. Donor lung bronchoalveolar lavage fluid (BALF) was obtained at the time of harvest, after perfusion of the donor lung with EuroCollins, immediately pretransplant, and after completion of the vascular anastomoses. Oxidized and total GSH levels in plasma and BALF samples were determined by a spectrophotometric assay. RESULTS: After reimplantation of the ischemic donor lung, there was a statistically significant increase in both GSSG and GSH in plasma samples, and a statistically significant increase in GSSG in the BALF. CONCLUSIONS: Compartmental differences between arterial and venous plasma, as well as the increase in GSSG in the BALF, implicated the lung that was transplanted as the source of oxygen free radical generation and GSSG release. Plasma GSSG levels seem to provide a sensitive, noninvasive, repeatable measure of ongoing tissue response and oxygen free radical production. PMID- 8000653 TI - Influence of burn injury on protein metabolism in different types of skeletal muscle and the role of glucocorticoids. AB - BACKGROUND: Negative nitrogen balance after burn injury mainly indicates muscle catabolism, but the exact influence of burn on protein synthesis and breakdown in different types of skeletal muscle and the role of glucocorticoids in this metabolic response are unknown. STUDY DESIGN: A 30 percent body surface area flame burn was inflicted on rats. Protein turnover rates were measured in vitro in the white fast-twitch extensor digitorum longus (EDL) muscle and the red slow twitch soleus muscle. To test the role of glucocorticoids, groups of rats were treated with the glucocorticoid receptor antagonist RU 38486 or vehicle. RESULTS: Burns resulted in reduced protein synthesis and stimulated protein breakdown, in particular myofibrillar protein breakdown, and the changes were substantially more pronounced in the EDL than in the soleus muscle. A burn-induced increase in muscle proteolysis was abolished by treatment with RU 38486, whereas the reduced protein synthesis was not affected by the glucocorticoid receptor antagonist. CONCLUSIONS: The results suggest that the white fast-twitch muscle is more sensitive to the effects of burn injury than the red slow-twitch muscle. Burn induced muscle proteolysis may be mediated, at least in part, by glucocorticoids, whereas protein synthesis is probably regulated by other mechanisms. PMID- 8000654 TI - Hepatic resection for hepatolithiasis and long-term results. AB - BACKGROUND: Hepatic resection is an established procedure for treating patients with hepatolithiasis. The long-term results after hepatic resection for hepatolithiasis were appraised. STUDY DESIGN: Of 127 patients with hepatolithiasis seen between 1973 and 1993, 43 patients underwent hepatic resection, and constituted the basis of this study. RESULTS: There was one operative death (operative mortality rate of 2.3 percent) and three deaths as a result of concomitantly associated cholangiocellular carcinoma. Of the remaining 39 patients, the complete stone clearance rate was 67 percent with operation alone, but reached 87 percent when cholangioscopy was used. Operative morbidity was recorded in five patients (12 percent), but they recovered with conservative therapy. Stones recurred in 15 percent of patients after a mean follow-up period of four years (range of three to six years). Eleven (28 percent) of 39 patients died after hepatectomy as a result of related diseases after a mean follow-up of 6.2 years. These 11 patients had associated biliary drainage procedures. They experienced a higher mortality rate (p < 0.05) than patients who did not have biliary drainage. CONCLUSIONS: We conclude that hepatic resection is adequate treatment for hepatolithiasis. The patients having additional biliary drainage procedures had a higher mortality, but one cannot reach conclusions about the negative effect of the drainage procedures because the drainage procedures were done in a selected and not a randomized manner. PMID- 8000655 TI - Improved outcome with fluid restriction in treatment of uncontrolled hemorrhagic shock. AB - BACKGROUND: Recent studies have challenged current guidelines for prehospital fluid resuscitation. However, long-term studies evaluating the consequences of fluid restriction in uncontrolled hemorrhagic shock are lacking. This study was done to examine the long-term effects of deliberate hypotension in the treatment of uncontrolled hemorrhage. STUDY DESIGN: Uncontrolled hemorrhagic shock was produced in 40 rats by a preliminary bleed (3 mL per 100 g) followed by 75 percent tail amputation. Experimental design consisted of three phases: a "prehospital phase" (90 minutes of uncontrolled bleeding with or without treatment with lactated Ringer's [LR] solution), followed by a "hospital phase" (60 minutes, including control of hemorrhage and fluid resuscitation including blood), and a three day observation phase. Forty rats were studied in four treatment groups (ten rats per group). Group 1 consisted of untreated controls (no resuscitation). Group 2 had no fluid during the prehospital phase. Group 3 had prehospital resuscitation to a mean arterial pressure (MAP) of 40 mm Hg with LR, and group 4 had prehospital resuscitation to MAP of 80 mm Hg with LR. Groups 2, 3, and 4 received fluid and blood to MAP of 80 mm Hg and hematocrit of 30 percent in the hospital phase. RESULTS: All rats in group 1 (untreated) died within 2.5 hours. Five rats in group 2 (no prehospital FR) survived 90 minutes; however, only one survived three days. In group 3, all ten rats survived 2.5 hours and six survived three days. In group 4, eight rats died within 90 minutes, but none survived long-term. Blood loss (mL per 100 g) for each group was 3.75 0.6 for group 1, 3.35 0.1 for group 2, 4.15 0.8 for group 3, and 8.45 0.6 for group 4, (p < 0.05, group 4 compared with groups 1, 2, and 3). CONCLUSIONS: Attempts to achieve normal MAP during uncontrolled bleeding increased blood loss, hemodilution and mortality. Hypotensive resuscitation resulted in less acidemia and improved long-term survival. PMID- 8000656 TI - Endoluminal pulse oximetry in ischemic colon in a swine model. AB - BACKGROUND: Postoperative sigmoidal ischemia after aortic grafting is a severe complication. No simple methods are available to detect this entity at an early stage. This study was done to monitor for sigmoidal ischemia with a new endoluminal probe based on pulse oximetry (SmO2). STUDY DESIGN: A prospective controlled animal study was done. Five pigs with low flow in the caudal mesenteric artery (20 percent of the basal flow) and four pigs in a control group were included. General and local circulatory parameters were monitored in the carotid and pulmonary artery and in the caudal mesenteric vein (CMV). Mucosal biopsy specimens were taken for histologic examination. Statistical analysis was done with the Wilcoxon and Mann-Whitney rank sum test and with analysis of variance. RESULTS: During the first two hours of ischemia, no sigmoidal pulse was detected. During the third hour, in three pigs the pulse curve reappeared with a SmO2 of 48 to 88 percent. After two hours, the mean oxygen saturation in the CMV of the ischemic group was 64 percent (compared with the control group, 77 percent, p < 0.05). After one hour, the mean lactate concentrations were 2.0 and 1.3 mmol per L, respectively (p < 0.05). Significant histologic changes occurred with neutrophilic infiltration in the crypts, in the lamina propria, and in the submucosa. CONCLUSIONS: Low-flow sigmoidal ischemia can be detected and monitored with endoluminal pulse oximetry in this model of early sigmoidal ischemia. PMID- 8000657 TI - Melanoma in black South Africans. AB - BACKGROUND: Scant data exists on melanoma in blacks from Africa. This study was undertaken to define factors affecting outcome of blacks from South Africa with melanoma. STUDY DESIGN: A retrospective analysis of the management and outcome of 63 black patients with malignant melanoma treated at a major referral center during a 14 year period is presented. Data evaluated included patient demographic and clinical characteristics, stage at presentation, tumor site, histologic type, treatment, and subsequent cure. Survival curves were calculated for stage and site of disease. RESULT: The mean age at presentation of the 39 women and 24 men was 60.5 years (range of 30 to 85 years), with a peak incidence in the sixth decade. The foot was the most common site of disease (45 patients). Seven patients had subungual melanoma, seven had primary mucosal lesions, and in six, the primary lesion could not be found. Thirty patients presented with stage I disease, two with stage II, 23 with stage III, and nine with disseminated metastatic disease. Acral lentiginous melanoma was the most common histogenetic type (34 patients), nodular melanoma occurred in ten patients, and superficial spreading melanoma occurred in three patients. The mean Breslow depth was 6.15 mm (range of 1 to 25 mm). Patients with localized disease were treated by wide local excision and split skin graft, while patients with melanoma in the nailbed were treated by amputation of the involved digit. Sixteen patients are alive after a mean follow-up period of 82.1 months, 44 have died after a mean of 12.7 months, and five patients have been unavailable for follow-up evaluation. CONCLUSIONS: The poor prognosis in black patients in South Africa is the result of delayed presentation with thick primary lesions and advanced disease. An active education program may reduce mortality by detecting the disease earlier. PMID- 8000658 TI - Evaluation of imaging examination for hepatic invasion of carcinoma of the gallbladder and postoperative patient outcome. AB - BACKGROUND: Hepatic invasion is an important factor in the selection of an operative procedure for patients with carcinoma of the gallbladder. Imaging modalities to detect the hepatic invasion were evaluated for accuracy, and postoperative patient outcome was analyzed. STUDY DESIGN: Thirty-six patients who were treated for carcinoma of the gallbladder at our institution between 1984 and 1993 were studied. The imaging results of ultrasonography (US), computed tomography, and angiography were compared with histologic findings regarding intrahepatic invasion of the carcinoma. RESULTS: Histologic examination of the operative specimens removed from 21 patients revealed that the detection of hepatic invasion with preoperative US was superior to that with the other two modalities. The preoperative US showed a diagnostic value that was almost the same as that of the intraoperative US. The postoperative patient outcome was not satisfactory, although extended radical operation was performed using image guidance in the 21 patients. The patients died as a result of nodal recurrence rather than hepatic recurrence. CONCLUSIONS: Preoperative US should be performed initially for detecting hepatic invasion from carcinoma of the gallbladder and can be substituted for intraoperative US. Considering the operative treatment for patients with carcinoma of the gallbladder, lymph node dissection is as important as the extent of hepatectomy. PMID- 8000659 TI - Single-dose cefotetan or cefoxitin versus multiple-dose cefoxitin as prophylaxis in patients undergoing appendectomy for acute nonperforated appendicitis. AB - OBJECTIVE: A prospective, double-blind study was performed to examine the effects of prophylactic cefotetan and cefoxitin in postoperative wound infection for patients with nonperforated acute appendicitis. METHODS: One hundred thirty-six of 179 patients with a clinical diagnosis of appendicitis were evaluated and divided into three groups: group 1 received 2 g cefotetan preoperatively, group 2 received 2 g cefoxitin preoperatively, and group 3 received 2 g cefoxitin preoperatively followed by three postoperative doses. RESULTS: The overall wound infection rate was 4.6 percent. Group 2 (single-dose cefoxitin) had a significantly higher wound infection rate (11.1 percent) than group 1 (single dose cefotetan) (zero percent) or group 3 (multiple-dose cefoxitin) (1.9 percent). CONCLUSIONS: Single-dose cefotetan and multiple-dose cefoxitin are equally effective. However, because of the greater convenience and markedly decreased cost, single-dose cefotetan is the prophylaxis of choice in appendectomy for nonperforated appendicitis. PMID- 8000661 TI - "Cluster" allografts. PMID- 8000660 TI - Primary hyperparathyroidism in patients who have received radiation therapy and in patients who have not received radiation therapy. AB - BACKGROUND: Primary hyperparathyroidism (HPT) occurs more frequently in persons who have been exposed to low-dose therapeutic radiation. Little information is available concerning whether or not the clinical, metabolic, and pathologic manifestations, as well as outcome, differ in these patients when compared with patients with sporadic HPT. STUDY DESIGN: Records from 438 unselected patients with primary HPT, who were treated from 1982 to 1993 were retrospectively analyzed. All patients prospectively received a standard questionnaire preoperatively and postoperatively concerning clinical manifestations and a history of radiation exposure. Forty-nine patients had a history of radiation exposure (rHPT), whereas 389 did not have sporadic HPT (sHPT). RESULTS: There was no difference in gender (36 women and 13 men versus 289 women and 100 men) or age (mean of 52 +/- 12 versus 57 +/- 16 years) in patients with rHPT or sHPT. Fatigue, neuropsychiatric disorders, memory loss, nocturia, and polyurea were more common in patients with sHPT (p < 0.05), whereas pain in joints was more common in patients with rHPT (63 versus 52 percent; p < 0.001). Serum calcium levels were similar (11.1 +/- 0.8 versus 11.2 +/- 0.8 mg per dL), but serum parathyroid hormone levels were higher in rHPT (448 +/- 14 percent of upper limit of normal versus 371 +/- 12 percent upper limit of normal). The parathyroid pathology was similar in the two groups (single adenoma 74 versus 72 percent, hyperplasia 14 versus 16 percent, and double adenoma 12 versus 12 percent in rHPT versus sHPT, respectively). Thyroid pathology was more common in the rHPT group (multinodular goiter 27 versus 7 percent and papillary thyroid carcinoma 14 versus 0.3 percent). Seven (1.8 percent) of patients not receiving radiation therapy treated by us had persistent HPT, but no patients receiving or not receiving radiation therapy had recurrent HPT during the follow-up period (six years). CONCLUSIONS: Patients who have HPT after radiation treatment have more thyroid neoplasms but are otherwise quite similar to other patients with primary hyperparathyroidism. PMID- 8000662 TI - Bile duct reconstruction in the management of choledochal cyst. PMID- 8000663 TI - Transmissible agents and the surgeon. PMID- 8000664 TI - Criteria for evaluation of health care legislation. PMID- 8000666 TI - Public participation in health care. PMID- 8000667 TI - Professional updating through open learning as a method of reducing errors in the administration of medicines. AB - Errors in administration of medicines can have repercussions for the patient, the nurse and the organization. Reducing the incidence of drug administration errors must be a constant endeavour on the part of nurses and the organization as a whole. The organization can be proactive in providing support for the nurse before errors occur through refresher courses, however, the cost-effectiveness of such courses should be considered. Traditional teacher-centred approaches may not encourage nurses to reflect upon their own practice, and may only entail attendance rather than participation at a study session. An approach to drugs administration update is proposed which employs an open learning format. Consideration of the mechanisms for preparing, disseminating and evaluating such programmes are provided. Quantitative data to support positive evaluation of the update programme is not yet available. Qualitative evaluation by staff who have undertaken the module is very favourable. Staff have indicated that they have been enabled to reflect on their own performance, at their own pace, and that they have enjoyed active participation in the learning process. The possible future, and potential benefits, of such programmes in a time of scarce resources is discussed. PMID- 8000665 TI - Preoperative endoscopic clipping for determining the resection line in early carcinoma of the esophagus. PMID- 8000668 TI - Enrolled nurses: where do they go from here? AB - This paper reviews the circumstances which have affected the development of and change in the role and status of enrolled nurses. Factors which have contributed to the drive to provide conversion pathways for enrolled nurses are examined and current opportunities are described. The paper highlights prospects for newly converted enrolled nurses and for those who do not wish to convert and argues that both groups continue to have educational and professional status needs which must be recognized and taken account of. PMID- 8000669 TI - Managing to care: the importance of using existing information to guide service provision for informal carers. AB - All managerial decisions are taken on the basis of the information that is available. It is important that managers use appropriate information to base their decisions upon about service provision to ensure efficient use of resources. This basic premise serves as a framework for examining how quantitative and qualitative information can be of help to nurse managers in taking these decisions in the context of developing services for informal carers. The current emphasis on surveys as a means of assessing client need is questioned and it is suggested that a wealth of evidence, relating to the experience of carers, already exists. Examples of accounts which express the needs of informal carers are presented and their utility, in terms of highlighting the carers' perspective, is discussed to reinforce the importance of utilizing this information. The paper concludes that nurse managers can use these sources as a basis for decision-making in the area of service provision and this may result in a more effective use of resources through a needs-based approach. PMID- 8000670 TI - Preparing for trust status--an investigation into the morale of nurses undergoing change. AB - The morale of nurses is a phenomenon often open to public comment without substantiated evidence. This study objectively explored the morale of nurses in a large district general hospital preparing for transition to National Health (NHS) Trust status. Information was sought using a 72-item questionnaire. The investigation was firmly centred around a structured theory which construes morale in terms of nine dimensions. The notion of morale being a construct synthesized of nine dimensions adds to the uniqueness of the study. Other studies fail to differentiate between the dynamic morale construct and the more complacent attitudes of job satisfaction. PMID- 8000671 TI - Contributors to satisfaction with management in hospital wards. AB - The purpose of this study was to identify management-related factors contributing to personnel satisfaction in hospital wards. The sample population consisted of the employees of 15 hospital wards in four medical departments. The wards were classified into two categories on the basis of the satisfaction of the personnel with the management: 'satisfied wards' (seven wards with a highly satisfied personnel, n = 124) and 'other wards' (eight wards, n = 186). The employees of 'satisfied wards' reported more innovative activities and continuous quality improvements, more possibilities to participate in decision-making, more efficient communication within the ward and between other units, and more managerial activities for promoting the well-being of the staff compared with the personnel of 'other wards'. According to the ratings of the nursing directors, the quality of patient care in the 'satisfied wards' was higher, but there were no differences in cost-effectiveness between the study groups. PMID- 8000672 TI - An overview of the information management and technology strategy for the National Health Service in the UK. PMID- 8000673 TI - Short-term growth phenomena in children. PMID- 8000675 TI - Update on muscle relaxants. AB - While our knowledge of the neuromuscular junction is increasing as a result of new experimental techniques, our understanding of neuromuscular blockade has progressed less dramatically. It is now evident, however, that some of the other concepts will have to be modified to take into account the findings of recent, simple clinical experiments. PMID- 8000674 TI - Barium examination of the small intestine. AB - Barium radiology remains the method of choice for the diagnosis and evaluation of many small intestinal disorders. Enteroclysis (small bowel enema) is proving to be a quick and efficient way of examining the small intestine. During enteroclysis the intestine is distended with barium contrast medium, clearly demonstrating any morphological changes that may be present. PMID- 8000676 TI - Schizophrenia and the environment. AB - Schizophrenia is more prevalent in urban than rural areas. For a generation this difference was thought to be due to the downward social drift of affected individuals. Recent research suggests that being born and brought up in an inner city area increases the risk of developing the illness, and brings into question the role of environmental hazards and social factors. PMID- 8000677 TI - Clinical problems in gastroenterology. PMID- 8000678 TI - Acute renal failure in children. AB - Acute renal failure is a rare complication of childhood illness. The underlying disorder may be amenable to treatment but the mainstay of management is supportive therapy, nutrition and early referral for dialysis. PMID- 8000679 TI - ECG clinic. PMID- 8000680 TI - Cytomegalovirus retinitis. AB - Cytomegalovirus retinitis is the most common ocular opportunistic infection in patients infected with human immunodeficiency virus and remains a significant cause of visual loss in patients with the acquired immunodeficiency syndrome. Drugs are now available to treat this condition and recent advances in delivery techniques offer promising alternatives to traditional methods. PMID- 8000681 TI - Doctors, pharmacists and the prescribing process. AB - Although there is evidence that collaboration between doctors and pharmacists results in the more cost-effective use of medicines, the input of pharmacists into the prescribing process remains informal and largely retrospective. This article discusses the current problems associated with the prescribing process and suggests a framework to formalise the input of pharmacists. PMID- 8000682 TI - Cuffed polyurethane catheter for ambulatory infusional chemotherapy. AB - This article describes the technique for inserting cuffed polyurethane catheters under local anaesthesia. A very low complication rate is seen with these catheters and patients tolerate the catheters and Cadd infusional pumps for continuous chemotherapy very well. PMID- 8000684 TI - Use of the LMA in a patient with a head injury. PMID- 8000683 TI - Necrobacillosis revisited. PMID- 8000685 TI - Definitions and difficult asthma. PMID- 8000686 TI - Complex aetiology of type 2 diabetes. PMID- 8000687 TI - From pilloried to the ideal post. PMID- 8000688 TI - A postpartum patient presenting for non-life-threatening surgery. PMID- 8000689 TI - [Bronchial asthma in adults: a disease caused by reflux?]. PMID- 8000690 TI - [Pulmonary aspergillomas. Analysis of 31 patients]. AB - Thirty-one patients with pulmonary aspergilloma were studied retrospectively, leading to the following main findings: 1) Men are most often affected (90% of cases). 2) Diagnosis occurs significantly more often when the patient is between 50 to 60 years of age. 3) Aspergilloma originates most often in residual pulmonary tuberculosis (74% of cases). 4) The incidence of hemoptysis was high (87% of patients). Traditional tomography afforded images that were diagnostically useful in 77.4% of the cases, whereas simple X-rays were useful in only 38.7%. 6) In 94% aspergilloma occurred in the upper lobes. 7) Aspergillus was found in respiratory secretions in 55%. 8) Serum samples were positive for Aspergillus precipitins in 94.4%. 9) Forty-eight percent did not meet criteria for surgical intervention. 10) Noteworthy features of the course of the disease were that spontaneous lysis occurred in 13.6% and that hemoptysis led to death in 9%. PMID- 8000691 TI - [Relations between nonspecific bronchial hyperreactivity, diurnal variation of peak expiratory flow and medication requirements in patients with mild asthma]. AB - To assess the relation between non-specific bronchial hyperreactivity, we recorded diurnal peak expiratory flow variation (PFV) and asthma symptoms in 36 individuals with mild allergic asthma. The patients were challenged with methacholine to induce decreases greater than 40% in FEV1, or until a maximum of 200 mg/ml had been administered. Over the next 14 days, PFV was measured three times per day and symptoms and inhaled salbutamol requirements were recorded. In the 11 patients with complete dose-response curves, the geometric mean of diurnal PFV variation (% mean range) was 5.0%; this parameter was 8.3% (p < 0.01) in the 25 subjects whose curves did not reach a plateau. A correlation (r = -0.56, p < 0.001) was found between PC20 and % mean range. PFV for the sample as a whole. In the 11 patients with complete curves, however, no correlation (r = -0.31, p = NS) between % mean range of PFV and PC20 was found. Nor could the plateau (r = 0.19, p = NS) or EC50 (r = -0.26, p = NS) be found for these patients. The geometric mean for PC20 in the 12 subjects who needed salbutamol throughout the 14-day study period after methacholine challenge was 1.06 mg/ml; this parameter was 1.32 mg/ml (p = NS) for those with no symptoms. A plateau was reached by 2 of the 12 patients who experienced asthma symptoms and in 9 of the 24 who were asymptomatic (p = NS).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8000692 TI - [Ventilation pattern at rest and respiratory response to hypercapnic stimulation after lung transplantation]. AB - We aimed to assess breathing pattern at rest by studying occlusion pressure after the first 100 miliseconds (P0.1) and ventilatory response to hypercapnia after lung transplantation. Seven transplanted patients were compared with a control group of 7 healthy subjects. The breathing pattern at rest after transplantation included a significant increase in minute volume (VE) at the expense of an increase in tidal volume (VT) and above all of mean inspiratory flow (VT/Ti). There were no significant differences in ventilatory response to hypercapnia between the 2 groups, although the response curves of both VE and VT to CO2 tended to slope downward. These results can be explained by the mechanics of ventilation in some subjects studied and by the effect of pulmonary denervation on ventilatory control. PMID- 8000693 TI - [Effects of CO2 on the rat diaphragm in vitro]. AB - Acidosis produced by an increase in CO2 concentration decreases contractility and increases the tendency to fatigue in striated muscle. It is not clear a what levels of CO2 this effect takes place, or in what experimental models it can be observed. In this study we examine the effect of increasing concentrations of CO2 on contractility and fatigue in strips of rat diaphragm in vitro. Six strips of diaphragm from a rat of low-weight were kept in organ bath and supramaximal stimuli of 1, 10, 50 and 100 Hz were applied while CO2 concentration was changed from 5% (29 mmHg), to 10% (48.3 mmHg) to 20% (102 mmHg). To study fatigue we applied 45 series of 50 Hz stimuli per minute for 15 minutes. We obtained these results: a) Contractility. Force of contraction was less with 20% CO2 than with 5% under a stimulus of 1 Hz. No significant differences were found for other concentrations or frequencies. b) Fatigue. Force of contraction decreases as CO2 concentration increased and significant differences were found for all 3 concentrations. The conclusions were: a) an increase in CO2 from 5% to 20% produces a significant decrease in force of contraction under conditions of low frequency stimuli and b) increases in CO2 concentration from 5% to 10 to 20% increase the muscle's susceptibility to fatigue. PMID- 8000694 TI - [Rounded nodular atelectasis: computerized tomography and magnetic resonance appearances]. AB - Rounded atelectasis is a rare form of lung collapse whose X-ray appearance can be confused with that of tumors, especially nodular forms. We studied 14 such lesions with computerized tomography, finding that all were rounded and subpleural, specifically in the thickened pleura visceralis. The radiological sign that was most useful for diagnosis was the arc of the proximal vessels in the direction of the lesion. Such an arc was present in all the cases we reviewed. Other radiological signs such as brightness of the surrounding parenchyma, loss of volume in the affected lobe and the presence of air bronchogram were found in 10, 7 and 7 patients, respectively. When the X-ray appearance clearly indicates a diagnosis of rounded nodular atelectasis, we recommend that no additional diagnostic procedure be made. Three lesions in our sample were studied by magnetic resonance, which revealed the characteristic hypointense curves in all sequences done on 2 patients. The usefulness of computerized tomography in the diagnosis of this entity relegates magnetic resonance to a second plane. PMID- 8000695 TI - [Nitric oxide: an important molecule in respiratory diseases]. PMID- 8000696 TI - [Extrinsic allergic alveolitis caused by Penicillium frequentans. Review and presentation of a case]. AB - We present a case of extrinsic allergic alveolitis due to Penicillium frequentans exposure (suberosis) at a cork factory. Diagnosis was based on clinical history, a restrictive spirometric pattern, evidence of reticular-nodular lung infiltrates on the X-ray, intradermal skin tests with dual reaction and precipitins-positive serum samples in the presence of the P. frequentans fungus. Although the patient refused to submit to a specific bronchial challenge, two natural challenges occurred when he once again happened to handle wet cork after leaving his previous job. The literature referring to this disease is reviewed. PMID- 8000697 TI - [Pulmonary leiomyosarcoma]. AB - We present the case of a young patient with leiomysarcoma of the lung that was at first diagnosed as a hydatid cyst. Pathological tissue analysis was needed for firm diagnosis. This rare tumor, of which fewer than 100 cases have been reported worldwide in the literature, needs to be considered as a differential diagnosis when lung cancer is suspected, given that leiomysarcoma has a better prognosis. Treatment is mainly surgical. PMID- 8000698 TI - [Varicella pneumonia in previously healthy adults]. AB - Two cases of pneumonia associated with chicken pox in previously healthy patients are described. Their known risk factor was heavy smoking. Both were treated successfully with parenteral aciclovir, although one presented a restrictive spirometric pattern with lowered DLCO that became normal 3 months after discharge. PMID- 8000699 TI - [Acute pulmonary toxicity caused by carbamazepine: apropos of a case]. AB - Pulmonary toxicity caused by carbamazepine seems to be a non dose-dependent process involving pulmonary infiltrates, eosinofilia and skin rash. We report a case with acute presentation that resolved successfully after the drug was withdrawn and the patient was treated with corticosteroids. Bronchoalveolar lavage showed an inversion of the lymphocyte ratio CD4/CD8 supporting the suggestion by other authors that drug-induced pulmonary toxicity. PMID- 8000700 TI - [Bronchiectasis in patients with severe alpha 1-antitrypsin deficiency: a frequent association?]. PMID- 8000701 TI - [Septic pulmonary embolism secondary to dental focus. Lemierre's syndrome?]. PMID- 8000702 TI - [Spontaneous massive hemothorax as initial manifestation of malignant pleural mesothelioma]. PMID- 8000703 TI - Progressive differentiation of human sebocytes in vitro is characterized by increasing cell size and altering antigen expression and is regulated by culture duration and retinoids. AB - Increasing cell size, lipid accumulation, and altered antigen expression are features of sebaceous differentiation in vivo. Enhanced lipid synthesis with progressive differentiation is also present in cultured human sebocytes. This study was conducted to investigate the evolution of cell size and antigen expression of human sebocytes with progressive differentiation in vitro. Subconfluent human sebocyte cultures were examined for sebocyte differentiation evaluated on cytocentrifuge preparations by light microscopy and classified in stages according to morphological criteria described for sebocytes in vivo. Rates of 5.1 +/- 2.2% undifferentiated sebocytes, 29.2 +/- 4.9% early differentiated, 20.7 +/- 4.1% advanced differentiated, 37.6 +/- 6.4% fully differentiated, and 5.9 +/- 1.9% mature sebocytes were calculated in secondary cultures. The size of cultured sebocytes measured by computer-assisted planimetry significantly increased with progressive differentiation up to 4-5.5 times. The low rates of mature sebocytes and the only moderate increase of their size with progressive differentiation indicate an incomplete terminal differentiation in vitro. Sebocytes were subsequently stained with a series of monoclonal antibodies (mAb) to determine antigen expression using the alkaline phosphatase anti-alkaline phosphatase technique. The number of sebocytes labeled with the anti-keratin mAb CK8.12 and KL1, and the mAb 34D11 (82 kD protein) increased with progressive differentiation; significant differences were found after comparing early and advanced differentiated sebocytes. Sebocytes were positively stained with the anti-keratin mAb 6B10 (K 4), RPN1162 (K 7), CK13 (K 13), RPN1165 (K 19), CK8.60, and the mAb 115F5 (MAM-6c), OM-1 (sebaceous gland antigen), and 24F10 (basic polypeptides) only at late-stage differentiation. The expression of keratins 4, 7, 13, and 19 was confirmed by gel electrophoresis and immunoblotting. The data obtained were used to study the effects of the duration of cultivation and of the retinoids isotretinoin and tretinoin on sebocyte differentiation in vitro. Subcultivation of sebocytes upregulated, and treatment with isotretinoin but not with tretinoin downregulated labeling with mAb which recognize indicating progressive and late-stage differentiation. PMID- 8000704 TI - Predominant usage of distinct T-cell receptor V beta regions by epidermotropic T cells in psoriasis. AB - To investigate the role of T cells in psoriasis, we analyzed the T-cell receptor (TCR) repertoire in peripheral blood lymphocytes (PBLs) and in skin lesions of 9 patients with chronic plaque-stage psoriasis by means of immunohistochemistry. An extended panel of monoclonal antibodies detecting 11 different V beta families was employed in this study. In the peripheral blood, no predominant TCR V beta expression was detected and interindividual differences were small. Skin infiltrating T cells showed only marginal differences in the TCR V beta usage when compared with PBLs. However, in 3 patients the intraepidermal infiltrate comprised up to 40% of T cells expressing a TCR V beta region which was virtually absent in the peripheral blood and the dermal infiltrate. Thus, although the TCR V beta usage of skin-infiltrating T cells showed little difference compared to PBLs, several cases exhibited a significant increase of epidermotrophic T cells using one particular V beta region. PMID- 8000705 TI - Effects of prostaglandin E1 on human keratinocytes and dermal fibroblasts: a possible mechanism for the healing of skin ulcers. AB - The effects of prostaglandin E1 (PGE1) on cell growth, cytokine production and interaction of cultured normal human keratinocytes (NHKs) and human dermal fibroblasts (HDFs) were investigated. When NHKs were treated with PGE1 directly, only a slight increase in cell growth and a transient decrease in interleukin 1 alpha (IL-1 alpha) secretion were observed. No IL-6 was detected either before or after PGE1 treatment. In addition, IL-8 and transforming growth factor alpha (TGF alpha) production were uninfluenced by PGE1. The response of HDFs to PGE1 differed from that of NHKs. Following PGE1 treatment, IL-1 alpha and TGF alpha from HDFs remained undetectable while IL-6 production was enhanced markedly. IL-8 production was also slightly enhanced. Exposure of HDFs to PGE1 for 96 hours significantly promoted cell proliferation. Two kinds of conditioned media (CM) were prepared by a brief feeding of HDFs with keratinocyte basic medium or Dulbecco's modified Eagle's medium supplemented with 5% FCS with or without PGE1. NHKs proliferated more rapidly in CM than in corresponding basic medium. Moreover, CM prepared with PGE1 treatment showed a stronger effect in promoting NHK proliferation than CM without PGE1 treatment. This promoting effect was inhibited by anti-human IL-6 monoclonal antibody dose-dependently. These results indicate that fibroblasts are more sensitive than keratinocytes in response to PGE1 and that, upon PGE1 stimulation, HDF-derived IL-6 may play an essential role in NHK cell proliferation which may at least partly account for the beneficial effects of PGE1 in the treatment of cutaneous ulcerations. PMID- 8000706 TI - Ontogeny of nerves and neuropeptides in skin of rat: an immunocytochemical study. AB - The sequence of maturation of nerves and appearance of neuropeptides was investigated in skin from fetal and neonatal rats by immunocytochemistry using antisera to protein gene product 9.5, substance P, calcitonin gene-related peptide (CGRP), vasoactive intestinal polypeptide (VIP) and neuropeptide Y (NPY). Immunoreactivity for PGP 9.5 appeared on fetal day 16 in face and nose, somewhat later (fetal day 19) in paws and tail. The sensory neuropeptides, CGRP/substance P (fetal day 19 and postnatal day 1, respectively) appeared earlier than the autonomic peptides VIP and NPY (postnatal day 7). Thus, the study shows that neuropeptides do not appear simultaneously with nerves and that the development is rostrocaudal. PMID- 8000707 TI - TNF alpha-induced activation of eosinophil oxidative metabolism and morphology- comparison with IL-5. AB - Human dermal mast cells are capable of releasing cytokines, particularly preformed TNF alpha, upon appropriate stimulation. Mast cell activation in vivo was shown to be associated with an influx and activation of inflammatory cells, initially PMN (polymorphonuclear neutrophilic granulocytes) then eosinophils. In order to learn more about the mechanisms by which TNF alpha is capable of activating eosinophils, in the present study the effect of TNF alpha on morphology and function of highly purified normal eosinophils (> or = 95%) was examined. As estimated by transmission and scanning electron microscopy, TNF alpha-stimulated eosinophils appeared to be strictly adherent and flattened exhibiting a characteristic "hemispheric" shape. TNF alpha induced a dose dependent, long-lasting production of reactive oxygen species as measured by lucigenin-dependent chemiluminescence (CL), even at a concentration of 0.001 U/ml. The maximal response upon stimulation with TNF alpha, however, was significantly lower than optimal effects induced by IL-5. TNF alpha-induced responses were completely inhibited by cytochalasin B and staurosporin, and partially blocked by pertussis toxin. Separation of eosinophils by discontinuous density gradients revealed the existence of at least two hypodense eosinophil populations with a distinct susceptibility to stimulation with TNF alpha. Based on functional assay systems, in contrast to a significant extracellular, only a small intracellular H2O2 production was detected. Accordingly, H2O2 production, detected by an ultrastructural technique, was observed only on the outer surface of the plasma membrane in the contact zones in between adjacent cells. Extracellular as well as intracellular production of H2O2 was completely inhibited by cytochalasin B. TNF alpha-induced activation of eosinophils is most probably mediated by binding to the 55 kD and the 75 kD TNF-receptor since both receptor molecules could be detected by FACS analysis and immune electron microscopy using receptor-specific antibodies. However, in contrast to its effect on eosinophil oxidative response, TNF alpha did not induce the release of significant concentrations of eosinophil cationic protein or eosinophil peroxidase in supernatants of cytokine-stimulated eosinophils, as detected by functional as well as immunological assay systems. These results clearly indicate that TNF alpha represents a potent eosinophil-activating cytokine which may be of relevance in the allergic inflammatory response. PMID- 8000708 TI - Contact sensitization induces proliferation of heterogeneous populations of hapten-specific T cells. AB - To characterize the T cells that are activated during the induction of contact hypersensitivity (CH), two sets of studies were conducted: 1) dinitrophenol (DNP) specific proliferative responses of T cells in draining lymph nodes of BALB/c mice sensitized epicutaneously to dinitrofluorobenzene (DNFB) were examined, and 2) from these lymph node cells, DNP-specific T cells were cloned by limiting dilution microculture and analyzed by FACS for surface markers, by RT-PCR, HT2 bioassay and ELISA for cytokine expression at mRNA and protein levels respectively, and by proliferation assay for cytokine and antigen-presenting cell (APC) requirements. Our results show that alpha beta TCR-bearing T cells of both the CD4+ and CD8+ subtypes from lymph nodes of DNFB-skin-painted mice proliferate specifically to dinitrobenzene sulfonate (DNBS) in vitro. Four DNP-specific, CD4+ T-cell clones were characterized: clone 5S4 secreted IL-4 and required Il-4 for optimal growth; clone 5S10 secreted IL-2 and required IL-2 for optimal growth; clone 5S2 secreted IL-4 but required IL-2 for optimal growth; and clone 5S8 secreted IL-2 predominantly at 5 months, but switched to production of IL-4 at 7 months. All four clones secreted IL-10, and proliferated to DNBS when Langerhans cell (LC)-enriched epidermal cells were used as APC. These findings indicate that heterogeneous populations of DNP-specific T cells are activated in draining lymph nodes during the induction of CH to DNFB in BALB/c mice. PMID- 8000709 TI - Phenobarbitone to gabapentin: a guide to 82 years of anti-epileptic drug pharmacokinetic interactions. AB - With the introduction of three new anti-epileptic drugs (AEDs) in the UK during the past 4 years as adjunctive add-on therapy, the possibility of AED pharmacokinetic interactions has become a relevant consideration. This review highlights the current status of AED interactions with particular emphasis on those interactions that are likely to be frequently experienced or whose outcome is potentially clinically significant. PMID- 8000710 TI - Psychosocial function following temporal lobectomy: influence of seizure control and learned helplessness. AB - Learned helplessness is the perception that one's behaviour cannot produce a desired outcome. Individuals with intractable epilepsy who have learned that the occurrence of a seizure is beyond their control can develop such a helpless attitude with cognitive, affective and behavioral components which may generalize to many aspects of life. Post-operative testing was done on 42 patients, aged 17 60 years with I.Q. > 80 who had temporal lobectomies (25 R, 17 L) with follow-up 1-14 years (mean 5 years). In addition to seizure outcome, psychosocial adjustment was measured using the Washington Psychosocial Inventory (WPSI) and a structured interview. Three variables of learned helplessness were also assessed: internal or external locus of control, resourcefulness, and depression. Seizure outcome was: completely seizure free, 36%; > 90% improvement, 38% < 90% improvement, 26%. Overall post-operative psychosocial adjustment was good, marked improvement in lifestyle was noted by 85%, personality change for the better by 65% and improved mood by 47%. A transient mood disorder was noted by 38% in the first six months following surgery. Psychosocial adjustment was better in patients who were seizure free or had > 90% reduction in seizures compared to those with < 90% improvement. Two measures of learned helplessness, depression and lack of resourcefulness correlated with poor postoperative psychosocial adjustment. Other variables beside seizure control must be considered in determining the ultimate outcome of epilepsy surgery. PMID- 8000711 TI - Practical problems of epilepsy management in children. AB - The problems associated with the investigation, diagnosis and treatment of epilepsy in children are considered in this paper, together with aspects of intellectual development. In addition, the difficulties encountered in family and school environments are reviewed. The problems which arise when medication is discontinued, and the possible importance of the loss, as well as the acquisition, of a condition, are also discussed. PMID- 8000712 TI - International differences in psychosocial well-being: a comparative study of adults with epilepsy in three countries. AB - Whilst studies from several countries illustrate the universality of psychosocial difficulties connected with an epilepsy diagnosis, there is a marked lack of empirical research findings on the subject of how different national populations compare on the same measuring instruments. This study reports on comparisons of the psychosocial well-being of samples of adults with epilepsy drawn from Britain (n = 392), the United States (n = 420) and New Zealand (n = 138) using scales assessing self esteem, life fulfilment, social and interpersonal difficulty, general physical health, worries and emotional well-being. The Americans with epilepsy revealed significantly lower levels of well-being than both the New Zealanders and the British. Using the multivariate statistical methods of discriminant and cluster analysis, the scales which were especially predictive of nationality were shown to be life fulfilment, worries, negative affect, and (to a lesser extent) general physical health. Differences between the three national groups were not apparent with regard to self esteem, social difficulty and positive affect. Some possible explanations for the results obtained are put forward. The findings imply that nation-specific variables should be addressed in studies of quality of life and epilepsy, and their effect alongside intra individual factors within other quality of life domains be ascertained. PMID- 8000713 TI - Vigabatrin use in 72 patients with drug-resistant epilepsy. AB - OBJECTIVE: To determine the efficacy of a new anti-epileptic medication vigabatrin in adults and children with drug-resistant epilepsy. DESIGN AND SETTING: An open, uncontrolled study in a tertiary referral clinic setting with vigabatrin used as add-on therapy. SUBJECTS: All persons with intractable epilepsy, predominantly with complex partial seizures, with or without secondary generalization. MAIN OUTCOME MEASURES: Outcome was assessed by the patient and physician in terms of reduction of seizure frequency and severity balanced against drug side effects. RESULTS: Of 72 patients studied, seven are seizure free and a total of 41/72 (57%) continue to take vigabatrin as they are deriving benefit therefrom. The results were most striking in patients with complex partial seizures with, or without, secondary generalization (65.6 and 60.9% ongoing treatment, respectively). Most of the 31 patients who ceased taking vigabatrin did so due to a lack of effect, but 9/31 did so because of adverse events: behavioural change, increased seizure frequency and oedema. CONCLUSIONS: Vigabatrin has a definite role to play in the management of persons with intractable complex partial seizures where standard anti-epileptic therapy has failed to achieve control. PMID- 8000714 TI - Epilepsy brain surgery: a Pittsburgh perspective. AB - The views of the authors are presented about the past history and recent situation of epilepsy brain surgery in the United States. Issues of efficacy and quality of life are reviewed, and little empirical evidence is found supporting epilepsy brain surgery as a cost-effective treatment modality. Prospective randomized clinical trials have not been run to address these issues and various problems with patient recruitment and funding seem destined to preclude them. PMID- 8000715 TI - Impact of lamotrigine on patients with refractory epilepsy: the Leicester experience. AB - We prospectively monitored our experience of lamotrigine as add-on therapy in 45 patients with refractory epilepsy. Nine patients (20%) withdrew from treatment due to adverse drug reactions and five patients (11%) withdrew because of a deterioration in seizure frequency. A further 17 patients (38%) showed little (< 25%) reduction in seizure number, eight patients (18%) showed a 25-50% reduction whilst 15 patients (33%) had a 50% or greater reduction in seizure number (P = 0.002). Lamotrigine was of greater benefit in patients with tonic-clonic seizures (seven of fourteen [50%] showed a > 50% seizure reduction; P = 0.01) than in patients with complex partial seizures (seven of 22 [32%] showed a > 50% seizure reduction; P = 0.02). Despite a high withdrawal rate due to ADRs, lamotrigine proved of significant benefit to one-third of our study group. PMID- 8000716 TI - Seizure suggestibility may not be an exclusive differential indicator between psychogenic and partial complex seizures: the presence of a third factor. AB - Differential diagnosis between psychogenic or ('hysterical') pseudoseizures and clinical partial complex seizures has often employed an index or inference of suggestibility. However, recent research indicates a moderate association between complex partial epileptic-like signs and hypnotic capacity in the normal population as well as for complex partial epileptic patients. Consequently, the precipitation of overt, non-stereotyped seizures by instruction may not be a reliable diagnostic method when an insidious process is slowly elevating temporal/limbic lobe lability. Implications for treatment and contra-indication of antipsychotic (D2 antagonist) drugs are discussed. PMID- 8000717 TI - Lack of potentiation of anticonvulsant effect by fluoxetine in drug-resistant epilepsy. AB - To test the hypothesis that fluoxetine may be a useful adjunct to antiepileptic therapy, we treated with fluoxetine (20-40 mg/day) nine patients suffering from medically intractable epilepsy with daily seizures. Five patients remained unchanged and four worsened. Worsening was more evident at 40 mg/day. One patient improved when receiving the lower dose (20 mg/day) and worsened with the higher dose (40 mg/day). These data suggest: (1) that fluoxetine is not effective as add on antiepileptic treatment; (2) that caution should be exerted when using fluoxetine as an antidepressive treatment in epileptic patients. PMID- 8000718 TI - The hazards of prescribing from serum levels. AB - Clinical audit at a mental handicap hospital suggested that doses of antiepileptic drugs were being altered in response to suspiciously high or low serum level results. In order to assess the reliability of such results, sequential serum levels for individual patients were examined for consistency. Correlation between results which should have been the same was found to be so low as to call into question the value of drug serum level sampling in this hospital. Investigation of the source of the variability continues. In the meantime, clinical staff are reminded that it is unsafe to make any decision on the basis of a single drug serum level. PMID- 8000719 TI - An open multicentre prospective study of the effects of monotherapy with controlled-release carbamazepine on newly diagnosed generalized tonic-clonic seizures. AB - In a prospective study, 139 patients who presented newly diagnosed primarily generalized tonic-clonic seizures (GTCS) were treated with monotherapy controlled release carbamazepine (CR-CBZ) (TegretolCR) during one year. Ninety-three patients completed the trial. Patients were assessed for seizure control and tolerance. Mean number of seizures in the year before entry into the trial was 2.42 +/- 1.69, during one year follow-up this number was 0.77 +/- 2.44 (n = 93). Total number of patients remaining seizure-free during 12 months was 72 out of 93 patients completing the trial. Overall efficacy and tolerance was rated by the investigators as excellent in the majority of patients (respectively 86% and 77%). The results suggest that TegretolCR might be a drug of choice for first line treatment of tonic-clonic seizures given the excellent efficacy and relative lack of toxicity. PMID- 8000720 TI - Diagnosing juvenile myoclonic epilepsy in an elderly patient. AB - Juvenile myoclonic epilepsy is a common idiopathic generalized epilepsy with age related onset of symptoms. We present an unusual case where definitive diagnosis was delayed until the patient was aged 66 years, despite early recognition of the clinical features. Although uncommon in the elderly, JME should be considered in all patients with seizures refractory to treatment. PMID- 8000721 TI - Antiemetic treatment for cancer chemotherapy: problems and progress. PMID- 8000722 TI - Supportive Care in Cancer indexed in Index Medicus and MEDLINE on the MEDLARS system beginning with Vol. 1, No. 1, 1993. PMID- 8000723 TI - Antiemetics in children receiving cancer chemotherapy. AB - Nausea and vomiting are debilitating side effects that often accompany the administration of chemotherapy and may lead to adverse physiological and psychological effects. Chemotherapy agents usually stimulate the chemoreceptor trigger zone, which then sends signals to the vomiting center in the medullary lateral reticular formation. The neurochemistry of vomiting involves serotonin and serotonin S3 receptors. Nausea and vomiting are difficult to treat once they have occurred, and prior poor antiemetic control may lead to future anticipatory nausea and vomiting. Thus, good antiemetic regimens must be prophylactic, scheduled, and individualized. Specific regimens must be adjusted to account for the emetogenic potential of the chemotherapy drug(s) being administered and the individual patient's preferences. The major classes of antiemetics include serotonin S3 receptor antagonists, phenothiazines and metoclopramide. Steroids are ineffective antiemetics alone but good potentiators of other antiemetics. We usually recommend a serotonin S3 receptor antagonist alone for less emetogenic regimens or in conjunction with dexamethasone for more emetogenic regimens. For breakthrough vomiting, we usually add lorazepam and/or scopolamine. PMID- 8000724 TI - Treatment of chemotherapy-induced emesis in the 1990s: impact of the 5-HT3 receptor antagonists. AB - Considerable progress has been made in the development of means to limit nausea and vomiting arising from cancer chemotherapy. A number of key conceptual advances in the last decade have been critically important. these include recognition of the value of combination antiemetic therapy, identification of important patient- and treatment-related factors predictive of emesis, and appreciation of the importance of serotonin (5-HT) in the pathophysiology of emesis and the value of selective antagonists of the type-3 serotonin receptor. Comparative trials of the 5-HT3 receptor antagonists and classic antiemetic agents have helped define optimal antiemetic approaches in a number of settings. A combination of a 5-HT3 antagonist and dexamethasone is the treatment of choice for patients receiving single- and multiple-day cisplatin. The 5-HT3 antagonists are also effective agents with noncisplatin chemotherapy. Clear-cut superiority to classic antiemetics such as dexamethasone has not been consistently demonstrated, however. Results with the 5-HT3 antagonists in cisplatin-induced delayed emesis have been disappointing to date. The results of ongoing prospective trials should define their role more clearly. At present a combination of metoclopramide and dexamethasone is the treatment of choice in this setting. Results of trials comparing 5-HT3 antagonists are beginning to emerge. Available information suggests no clinically relevant differences in antiemetic efficacy between these agents. Many questions regarding the optimal use of the 5-HT3 antagonists and their integration into clinical practice remain unanswered and are the appropriate focus for additional study. PMID- 8000725 TI - Are there differences among the serotonin antagonists? AB - The serotonin-receptor (5-HT3) antagonists combined with dexamethasone are considered the antiemetic therapy of choice in the prevention of cisplatin induced emesis. As there are now several compounds on the market, the dilemma of preference is particularly relevant. In preclinical studies some differences among the three marketed drugs (ondansetron, granisetron and tropisetron) have emerged. In particular, tropisetron and granisetron have a greater potency and duration of action and seem to have a greater selectivity toward the 5-HT3 receptor with respect to ondansetron. Furthermore, while with tropisetron and granisetron there is a linear dose/response relationship, this does not seem to be the case for ondansetron. These preclinical differences, however, do not seem to correlate with the clinical antiemetic activity of these compounds. In fact, although the number of comparative studies is small, with all of them presenting several shortcomings (small number of patients, not blinded studies, no association with steroids, sponsored trials), it seems that the antiemetic activity and tolerability of ondansetron, granisetron and tropisetron is very similar. If these data are confirmed, the least expensive of the 5-HT3 antagonists should be the drug of choice. We feel, however, that the answer to this rather difficult question of choice will come from very large, independent, methodologically correct studies designed to show small but clinically significant differences (i.e., less than 10% in complete protection from emesis). These trials, which require about 1000-1500 patients, are ongoing and the one carried out as a multicenter study by the Italian Group for Antiemetic Research is close to conclusion. PMID- 8000727 TI - Future of the management of emesis. AB - Development of effective antiemesis has depended upon identification of critical neurotransmitter receptors within the emetic reflex arc. Investigations of cholinergic, histaminergic, dopaminergic, and serotonergic receptors led to our present generation of antiemetics. Opiate and adrenergic receptors are the likely targets of the next generation of antiemetics. The recently identified critical neurotransmitter receptors (opiate, adrenergic, and serotonergic) also provide a link to cancer pain, anticipatory vomiting, and cancer anorexia respectively. Future collaborations are likely to include investigators from various areas of supportive care working together on these common problems. PMID- 8000726 TI - Delayed emesis following anticancer chemotherapy. AB - As the control of acute chemotherapy-induced emesis has improved, delayed emesis (occurring 24 h or more after treatment) has become the most bothersome vomiting problem. Delayed vomiting occurs after treatment with many anticancer drugs, but has been most often studied following cisplatin or combinations of cyclophosphamide and anthracyclines. The mechanism of this phenomenon is unknown. Empirical trials of antiemetic agents effective in controlling acute emesis identified the combination of metoclopramide and dexamethasone as useful in lessening delayed emesis after displatin in a randomized, placebo-controlled study. The specific serotonin receptor (5-HT3) antagonist ondansetron yielded results equivalent to the prior placebo results in a phase II trial using identical methodology in similar patients given cisplatin. Following anthracycline and cyclophosphamide combination chemotherapy, the delayed vomiting prevention observed with dexamethasone alone exceeds that of ondansetron. These observations suggest that delayed emesis is primarily mediated by neurotransmitters other than serotonin. Since delayed emesis occurs more frequently in patients who experience nausea and vomiting on the day they receive chemotherapy, tested combination antiemetic regimens, employing a 5-HT3 antagonist (either granisetron, metoclopramide, ondansetron or tropisetron), dexamethasone, and a benzodiazepine (lorazepam and alprazolam) should be routinely employed. This approach provides the best protection for acute and delayed emesis. Further research, looking beyond the specific 5-HT3 antagonists, provides the best strategy to improve the control of delayed symptoms. PMID- 8000728 TI - Costs and benefits of antiemetic therapy. AB - Allocating part of the diminishing resources of the health-care system to new therapeutic approaches needs a decision analysis which should be understood by all partners. This paper defines some of the economic evaluation methods used recently. Through examples of cost/effectiveness and cost/benefit studies performed in the U.K. and Switzerland it shows that, in the European environment at least, specially now that prices are decreasing, serotonin-receptor (5-HT3) antagonists can and should be used to prevent acute nausea and vomiting. PMID- 8000729 TI - Costs and benefits of outpatient therapy. AB - In recent years, much of the care traditionally rendered in hospitals has been shifted to ambulatory settings. This change has been fueled as much by changing patterns of reimbursement as by rapid developments in medicine and technology. The current climate of health-care reform suggests that this trend will continue for the near future. Unfortunately, there are few studies that systematically evaluate the cost effectiveness or benefits of ambulatory care. Among the few such studies published to date, the results are not overwhelmingly positive. While the monetary costs of ambulatory care are generally far lower than inpatient management, several studies suggest that family and household disruption are prominent features of outpatient strategies. Thus, the measurement of the direct and indirect costs and benefits of ambulatory treatment presents a significant challenge to researchers. Development of methodologies to support such studies must be among our highest priorities. PMID- 8000730 TI - New developments in the assessment of pain in cancer patients. AB - Pain occurs in more than 80% of cancer patients before death. During recent years major progress has taken place in our techniques for the adequate assessment of cancer pain. Major prognostic factors associated with the pain syndrome have been recognized. In addition, other prognostic factors associated with the characteristics of the patient have been defined. Valid tools have been developed that allow for the assessment of most of the prognostic variables associated with analgesic response. During recent years a major effort has been made to integrate the pain syndrome within the other complex symptoms that are often present in patients with advanced cancer. The interaction of pain and analgesic treatment with other symptoms and their management is discussed. Finally, areas where future research should focus in the area of the diagnosis and assessment of pain are discussed. PMID- 8000732 TI - Autoantibodies and rheumatology. PMID- 8000731 TI - Overview of current development in patient-controlled analgesia. AB - Over the past two decades, numerous trials have assessed the safety and efficacy of patient-controlled analgesia (PCA). Advantages over conventional parenteral narcotics reported from these trials include equivalent to superior pain relief, superior patient satisfaction, decreased sedation and anxiety, faster return to normal functional status, and reduction in nursing time and hospitalization. The majority of these trials have been conducted in the postoperative patient population. In the mid to late 1980s, interest arose in applying PCA technology to the management of cancer pain. Factors that served as an impetus for the use of PCA in cancer pain included favorable reports from the postoperative setting and the often-cited statistics regarding the magnitude of the cancer pain problem. Advances in PCA technology coupled with advances in vascular access technology that allow the placement of long-term ports and catheters to facilitate intravenous, epidural, or intrathecal administration of opioid analgesics have made the applicability of PCA in ambulatory cancer patients an attractive option. The greatest breakthrough in PCA technology came with the introduction of devices making it possible to choose between intermittent (demand bolus) and continuous administration (continuous infusion) or both intermittent and continuous modes. A comparison of these types of PCA devices is described. The limitations of the literature involving PCA therapy in cancer patients make it difficult to identify optimal patient selection criteria, PCA administration schedules, drug selection and dosing, and optimal route of administration. The current status and pertinent issues related to these topics are addressed. PMID- 8000734 TI - Pharmacogenetics: what role in rheumatology? PMID- 8000733 TI - Therapeutic impasse in osteoarthritis. PMID- 8000735 TI - Sibling pair analysis shows no linkage of generalized osteoarthritis to the loci encoding type II collagen, cartilage link protein or cartilage matrix protein. AB - Generalized OA (GOA) is a well-characterized subset of primary OA which is strongly associated with the occurrence of Heberden's nodes. Using gene-specific highly polymorphic markers and affected sib pair (ASP) analyses, we have investigated genetic linkage between GOA and three cartilage matrix genes: COL2A1 which encodes type II collagen; CRTL1 which encodes the cartilage link protein and CRTM which encodes the cartilage matrix protein. The analyses showed no linkage between GOA and the three genes in the 38 sib pairs examined. Since we examined a relatively modest number of sib pairs, our results can only exclude COL2A1, CRTL1 and CRTM as major susceptibility loci for GOA. PMID- 8000736 TI - A longitudinal study of cartilage matrix metabolism in patients with cruciate ligament rupture--synovial fluid concentrations of aggrecan fragments, stromelysin-1 and tissue inhibitor of metalloproteinase-1. AB - This is the first study which quantifies aggrecan fragments, stromelysin-1 and tissue inhibitor of metalloproteinases-1 (TIMP-1) in SF samples prospectively obtained from the same patient at different time intervals after a cruciate ligament injury of the knee. Aggrecan fragment concentrations were determined by dye precipitation with Alcian Blue. Stromelysin-1 and TIMP-1 were analysed by immunoassay. Ten healthy volunteers formed the reference group. Immediately after knee injury, all marker concentrations were higher as compared to the reference group. The high marker concentrations decreased gradually with time, and in samples obtained between 6 months and 6 years after the injury, median concentrations of some of the markers were not different compared to reference levels. This was in contrast to results from previous cross-sectional studies, where chronic phase median concentrations of all markers were consistently higher than reference levels. In previous cross-sectional studies, however, the samples were obtained at arthroscopy done because of knee complaints at different times after a knee injury. In the present study, the knee injured patients visited the orthopaedic outpatient ward only for SF sampling, and they had no or only minor knee symptoms. We conclude that the temporal changes of marker concentrations in joint fluid after knee injury, suggested from cross-sectional studies, have now been confirmed in a longitudinal, prospective cohort study. We further find that in patients with mild knee symptoms in the chronic phase after cruciate ligament injury, median SF levels of aggrecan fragments, stromelysin-1, and TIMP-1 are lower than in patients with significant knee complaints after the same type of injury.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8000738 TI - Prevalence of selected autoantibodies in different elderly subpopulations. AB - We have evaluated the prevalence of selected autoantibodies commonly utilized in rheumatologic practice in different elderly subpopulations grouped according to their clinical status. RF, ANA, double-stranded DNA antibodies, and antibodies to extractable nuclear antigens (ENA) were measured in the serum of all participants using standardized laboratory assays. One hundred and fifty-nine elderly subjects were enrolled, of whom 63 were classified as successfully aging elderly, 62 were ambulatory chronically ill residents of a nursing or Veterans home and 34 were patients attending an RA clinic. Prevalence of autoantibodies were compared to healthy adult blood donors. There was no statistically significant increase in autoantibodies in successfully aging elderly compared to healthy young controls. RF, ANA and ENA antibodies were significantly increased in only the chronically ill and RA sufferers. Antibodies to nDNA were absent in all groups. We conclude that autoantibodies commonly utilized in rheumatological practice are not globally non-specifically increased as a result of aging, but increase in prevalence in chronically ill elderly. Therefore assessment of health status is necessary to evaluate the clinical significance of these autoantibodies in the elderly. PMID- 8000737 TI - Long-term follow-up of 46 patients with anti-(U1)snRNP antibodies. AB - The records of 46 patients with anti-(U1)snRNP antibodies and a minimal period of follow-up after first clinical presentation of at least 5 yr were examined with emphasis on symptoms contributing to established criteria of SLE, systemic sclerosis (SSc), RA or dermato- or polymyositis (DM/PM). At first clinical presentation 13 (28%) of the 46 patients studied fulfilled ARA-criteria for SLE (n = 10), RA (n = 2) and SSc (n = 1), and 33 (72%) were classified as mixed connective tissue disease (MCTD). During follow-up 18 patients initially classified as MCTD were now classified as SLE (n = 5), SSc (n = 7), RA (n = 3), or a combination of these disorders (n = 3). A transformation of MCTD towards these connective tissue diseases occurred 2.6 +/- 3 yr (mean +/- S.D.) after first clinical presentation. At the end of the follow-up period 67% of the patients fulfilled ARA criteria for SLE, SSc, RA or a combination of these diseases. The majority of patients with anti-(U1)snRNP antibodies have or will develop a classified connective tissue disease within 5 yr after clinical presentation. This undermines the concept of MCTD being a distinct clinical entity. PMID- 8000739 TI - HLA-DRB genes and antiribosomal P antibodies in systemic lupus erythematosus. AB - Antibodies to the ribosomal P protein are specific for SLE but their prevalence varies in different ethnic groups. In a group of Chinese SLE patients from Malaysia who have a high prevalence of this antibody, we have found an increased frequency of an uncharacterized HLA-DRB gene allele, DR16X, in patients who are positive for anti-P antibodies compared to antibody negative patients (31.3% vs 3.2%, P < 0.01, Pcorr not significant, relative risk = 13.6). DR16X has only been found in south east Asian populations and may be a genetic factor which influences the high prevalence of anti-P antibodies in Chinese. PMID- 8000740 TI - Synovial fluid muramic acid in acute inflammatory arthritis. AB - Presence of muramic acid, a bacterial cell wall component, was analysed by gas chromatography-mass spectrometry in synovial fluid (SF) of 40 patients with acute inflammatory arthritis. SF muramic acid was observed in 4/14 patients with acute, culture negative inflammatory arthritis of unclear origin. Each of these four patients had a history of a recent bacterial disease (pansinuitis, purulent leg ulcer, erysipelas, unexplained fever with suspicion of cholecystitis and urinary tract infection). In the bacterial arthritis, SF muramic acid was detected in 6/12 patients (in 2/6 culture negative cases). In the reactive arthritis due to Salmonella or Yersinia, the rate of positivity was 2/14. Nineteen samples of traumatic SF effusion were muramic acid negative. These findings indicate that several cases of undefined acute inflammatory arthritis are of bacterial origin. PMID- 8000741 TI - Familial scleroderma--evidence for environmental versus genetic trigger. AB - Families with more than one case of scleroderma are unusual. Four families each with two members (in one case monozygotic twins) with scleroderma (systemic sclerosis, SSc) were identified. Clinical, immunogenetic and autoantibody studies were carried out. Multicase SSc families cited in the literature were reviewed. Each family pair shared cutaneous subset of disease severity, and SSc-associated autoantibody. HLA typing showed two pairs shared an HLA-DR allele associated with scleroderma (DR3 or DR5), while one also had alleles reported in association with their SSc-specific autoantibody. Review of dates and ages of onset suggested that the timing of onset of scleroderma is more likely to have an environmental trigger than to be encoded genetically. PMID- 8000742 TI - Reactive arthritis following an outbreak of Salmonella infection in Finland. AB - The incidence and clinical features of reactive arthritis (ReA) following an outbreak of enteritis caused by Salmonella enterica ssp. enterica serovar 4,5,12:b:-were studied in the autumn of 1992. The outbreak occurred in several municipalities and originated from sprouted mung beans. A questionnaire on extra enteric manifestations such as joint and eye symptoms was mailed 2 to 5 months after the outbreak to all bacteriologically proven cases. Two hundred and forty six of the 272 (90%) subjects responded to the questionnaire; 224 (91%) reported having had enterocolitis, 22 (9%) were asymptomatic. Sixteen subjects fulfilled the criteria for ReA, and one had irities only. Thus, the incidence of ReA/iritis after S. enterica was 6.9%. Only four of the 155 (3%) subjects aged less than 16 yr developed ReA, as compared with 12 of the 91 (13%) older patients (P < 0.001). The only patient with iritis was also more than 16 yr old. The joint symptoms were oligoarticular in 10 (63%), monoarticular in five (31%) and polyarticular in one (6%). The most frequently affected joints were the wrists, knees and ankles. Joints of upper extremities only were affected in three (19%), of the lower extremities only in six (37%) and of both in seven (44%) subjects. In the majority of the patients ReA was mild. The joint symptoms persisted for less than 1 month in six, 2 to 6 months in five and more than 6 months in five. Thirteen subjects with ReA/iritis were tissue-typed for HLA; four (33%) had HLA B27.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8000743 TI - Osteoarthritis of the scapho-trapezial joint. AB - In a cohort of 199 patients with OA we studied the prevalence of radiographic scapho-trapezial joint osteoarthritis (STJ OA) and its clinical features. The prevalence of STJ OA was 38%. Lone STJ OA occurs but is uncommon (11%). In contrast, STJ OA in combination with first carpo-metacarpal joint OA was found in 27%. There appears to be an age-related progression from those without disease to lone disease to combined disease. The most frequent radiological features seen were joint space narrowing, subchondral sclerosis and osteophytes. There was a weak correlation between STJ OA and palpable swelling at the thumb base (phi = 0.231, P = 0.01) but no association was found between STJ OA and tenderness at the thumb base. PMID- 8000744 TI - Osteoarticular penicilliosis marneffei. A report of eight cases and review of the literature. AB - Penicillium marneffei, a dimorphic fungus that is endemic in Southeast Asia and the southern part of China, can cause infections in both healthy and immunocompromised hosts. Bone and joint infections caused by this fungus have rarely been described. The clinical features of eight patients with bone and joint infections caused by this fungus are reported. The English literature on P. marneffei osteoarticular infection is reviewed. PMID- 8000745 TI - High mortality with systemic lupus erythematosus in hospitalized African blacks. AB - This survey was undertaken to determine the clinical spectrum and outcome of SLE in hospitalized African blacks in Durban, South Africa. We reviewed the hospital records of all patients with SLE who were seen during 1984 and 1990. Eighty-five patients were seen and their mean age at diagnosis was 33.3 years. The prevalence of the various diagnostic criteria was as follows: cutaneous, 68%; arthritis, 66%; renal, 65%; serositis, 29%; neuropsychiatric, 21%; haematological, 71%; immunological, 49%; anti-nuclear factor, 98%. Follow up data were not available in many patients but 25 (29%) are known to have died. The commonest causes of death were renal, infection, neurological and cardiac. This survey shows that SLE is being recognized more frequently in African Blacks and is associated with a high mortality. PMID- 8000746 TI - Acute effects of single dose nifedipine on cold-induced changes of microvascular dynamics in systemic sclerosis. AB - Calcium-channel blockers are widely used in the treatment of systemic sclerosis (SSc), but their in vivo influence on microcirculation is not fully elucidated. We evaluated the acute effect of nifedipine on the cold-induced changes of microvascular dynamics in SSc. Eleven SSc patients and seven healthy volunteers were studied. Dynamic aspects of the nailfold microcirculation (appearance time at the nailfold, transcapillary diffusion, interstitial distribution and interstitial clearance of sodium fluorescein given i.v.) were quantitatively assessed by a computer-aided fluorescence videomicroscope. Fluorescent light intensities (FLIs) at predefinite pericapillary and interstitial sites were measured under three experimental conditions: (1) baseline; (2) after cold test; (3) after single oral administration of 10 mg of nifedipine 5 min before cold exposure. The interval between the intravenous injection of sodium fluorescein and the first appearance of the dye at the nailfold significantly increased after cold exposure in the SSc patients (224.1 +/- 182.3 s vs 27.5 +/- 25.1 s at baseline) (P = 0.0026), but not in the controls (28.0 +/- 13.3 s vs 29.6 +/- 12.4 s at baseline). The effect of cold exposure on the appearance of the dye was not significantly antagonized by nifedipine (112.7 +/- 91.8 s) in the SSc patients (P = 0.07). Cold exposure significantly decreased transcapillary diffusion and interstitial distribution of sodium fluorescein in the SSc patients (P < 0.016), but not in the controls. The cold-induced changes of FLI values were antagonized by nifedipine in the SSc patients (P < 0.016), but not in the controls.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8000747 TI - The analgesic effect of acupuncture in chronic tennis elbow pain. AB - The immediate analgesic effect of a single non-segmental acupuncture stimulation treatment on chronic tennis elbow pain was studied in a placebo-controlled single blind trial completed by 48 patients. Before and after treatment, all patients were examined physically by an unbiased independent examiner. Eleven-point box scales were used [13] for pain measurement. Patients in the verum group were treated at non-segmental distal points (homolateral leg) for elbow pain following Chinese acupuncture rules, whereas patients in the placebo group were treated with placebo acupuncture avoiding penetration of the skin with an acupuncture needle. Overall reduction in the pain score was 55.8% (S = 2.95) in the verum group and 15% (S = 2.77) in the placebo group. After one treatment 19 out of 24 patients in the verum group (79.2%) reported pain relief of at least 50% (placebo group: six patients out of 24). The average duration of analgesia after one treatment was 20.2 h in the verum group (S = 21.54) and 1.4 h (S = 3.50) in the placebo group. The results are statistically significant (P < 0.01); they show that non-segmental verum acupuncture has an intrinsic analgesic effect in the clinical treatment of tennis elbow pain which exceeds that of placebo acupuncture. PMID- 8000748 TI - Abnormal microvascular responses in a lateral epicondylitis. AB - The laser Doppler flowmeter, an instrument highly sensitive to changes in blood flow velocity in the dermal microvascular bed, was used to examine a sympathetic vasomotor response (SVR) in 40 patients with lateral epicondylitis. There was a significant association between the absence of a normal SVR in the skin overlying the affected enthesis compared with the unaffected contralateral epicondyle (P < 0.01). These results suggest that local dysfunction of the sympathetic nervous system may be associated with the pathogenesis of anatomically discrete pain in the enthesopathy of epicondylitis. PMID- 8000749 TI - How does neurophysiological assessment influence the management and outcome of patients with carpal tunnel syndrome? AB - The objective of this study was to determine how neurophysiological assessment influenced the management and outcome of 100 consecutive patients referred to a department of clinical neurophysiology in a district general hospital with a provisional clinical diagnosis of carpal tunnel syndrome. Nerve conduction studies excluded the diagnosis in 36 patients who may have otherwise received inappropriate treatment. The decision whether to perform a carpal tunnel decompression was greatly influenced by a positive study. Symptoms subsequently resolved in 72-86% of patients treated on this basis, depending on the mode of treatment and the nerve conduction study findings, with similar outcomes for surgical and conservative measures. The clinical and estimated resource implications of this diagnostic service were found to be substantial. PMID- 8000750 TI - Effect of energy conservation and joint protection education in rheumatoid arthritis. AB - As there is relatively little information about the effectiveness of occupational therapy (OT) in RA a questionnaire was devised to assess whether patient knowledge and performance of joint protection manoeuvres improved following OT intervention and, if improved, whether this was sustained over 6 months. A photographic multiple choice questionnaire was devised covering major categories of activities of daily living. The study population consisted of 55 patients with RA attending a rheumatology clinic who had not previously had OT treatment. Patients had a single instruction/treatment session with an occupational therapist of 1-h duration. Prior to treatment the questionnaire was administered by an independent assessor who re-administered the questionnaire 1 month and 6 months after the OT session. Following treatment there was a significant increase in scores at 1 month compared with pre-treatment (P < 0.001). There was no significant change in score at 6 months compared with 1 month. Qualitative analysis of age and sex showed no significant effects. OT leads to sustained improvement in patient knowledge and probably performance of joint protection manoeuvres in RA. PMID- 8000751 TI - Hereditary arthro-ophthalmopathy (Stickler syndrome): a diagnosis to consider in familial premature osteoarthritis. AB - A number of factors contribute to the pathogenesis of osteoarthritis. Genetic factors are predominant in some cases, including the syndrome of hereditary arthro-ophthalmopathy. The clinical features of the syndrome and the concept of genetic mutations in matrix components are discussed. PMID- 8000752 TI - Effect of national health service reforms on outpatient rheumatology workload. South West Regional Advisory Committee for Rheumatology. AB - In order to compare the rheumatology outpatient workload in the South West Regional Health Authority in the years before and after implementation of the NHS reforms in April 1991, surveys were undertaken to collect and compare data from all NHS outpatient consultations during November in 1988, 1990, 1991 and 1992. All patients seen in consultation at all hospital rheumatology outpatient clinics in the South Western Regional Health Authority were included. Results were adjusted for both the number of working days in each month and the inclusion of one new centre in 1992. There was an increase of 33% in total consultations (2663 to 3551) between 1988 and 1992, mostly occurring following implementation of the NHS reforms. This increase related to both follow-up consultations and new patient consultations which increased by 26%. Conversely, waiting time from referral to a new patient consultation increased by 22% (65 days to 79 days). The case mix in most centres showed a proportional reduction in new patients with polyarthritis (43 to 34%) and an increase in back problems (10 to 15%) and OA (14 to 18%) but polyarthritis continued to dominate follow-up cases (75 and 72%). The overall follow-up: new ratio increased from 3.7 to 4.1. Contrary to early fears amongst rheumatologists, their workload has substantially increased during the time of this survey, and the waiting time for new referrals has also increased. While the proportion of new referrals with polyarthritis was reduced, the absolute number of such referrals has increased. As these patients are currently managed by long-term follow-up they make increased demands on hospital resources.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8000753 TI - The arthropathy of the Muckle-Wells syndrome. AB - Muckle-Wells syndrome (MWS) is a rare condition characterized by urticaria, arthralgias, deafness and amyloid nephropathy. The arthropathy is poorly documented. We describe the arthropathy occurring in four cases of MWS and discuss the management. Each patient developed recurrent bouts of transient synovitis. One patient developed a persistent sterile pyoarthrosis. PMID- 8000754 TI - Treatment of keratoconjunctivitis sicca: the use of a simple self-administered eye irrigation system. PMID- 8000755 TI - A case of date palm thorn-induced extra articular synovitis with rice grain bodies. PMID- 8000756 TI - Polymyositis presenting as bilateral trigeminal neuropathy. PMID- 8000757 TI - Impaired proprioceptive acuity at the proximal interphalangeal joint in patients with the hypermobility syndrome. PMID- 8000758 TI - Soluble intercellular adhesion molecule-1 in a geographical cluster of scleroderma. PMID- 8000759 TI - Spinal nerve root compression as onset of monostotic Paget's disease. Computed tomography and magnetic resonance image findings. PMID- 8000760 TI - Barium X-ray study of the small bowel in patients with rheumatoid arthritis taking non-steroidal anti-inflammatory drugs did not disclose ulceration. PMID- 8000761 TI - Lupus-like syndrome associated with the use of minocycline. PMID- 8000762 TI - Cushingoid picture with Proresid. PMID- 8000763 TI - Henoch-Schonlein purpura-like disease representing a flare of Behcet's disease. PMID- 8000764 TI - Gonadotrophin-releasing hormone agonists induce osteoporosis. PMID- 8000765 TI - Seronegative symmetrical polyarthritis with pitting oedema associated with antinuclear antibodies and a past history of giant cell arteritis. PMID- 8000766 TI - Chylous shoulder joint effusion treated by radiosynovectomy. PMID- 8000767 TI - Clinical significance of autoantibodies in systemic lupus erythematosus. PMID- 8000768 TI - The Northwick Park Neck Pain Questionnaire, devised to measure neck pain and disability. PMID- 8000769 TI - Development of an adolescent inpatient sexual abuse group: application of Lewin's model of change. AB - The development and implementation of an adolescent sexual abuse group on an inpatient psychiatric unit is described. Steps of Kurt Lewin's model of change are used as a framework for this planned change. Specific issues concerning group procedure and process are detailed. Recommendations for this group and broader use of the Lewin model are included. PMID- 8000771 TI - Are we ready for healthcare reform? PMID- 8000770 TI - Superkids: short-term group therapy for children with abusive backgrounds. AB - Many children who are hospitalized have a history of physical or sexual abuse. A short-term therapy group for children with abusive backgrounds, called Superkids, was led by nurse therapists using a combination of active role playing, masks, picture drawing, and discussion. The group was structured and covered five topics over a 2 1/2 week period: shame, anger, fear, trust and love. Clinical observations suggest that the Superkids group structure helps children talk about their feelings and the abuse they have suffered. Through a brief intervention group, members learn they are not alone and that they are accepted by their peers. PMID- 8000772 TI - Family preservation and support services. PMID- 8000773 TI - An interview with Sandra Weiss, PhD, DNSc, RN, FAAN. Interview by Patricia C Pothier. PMID- 8000774 TI - Tricyclic antidepressants: cardiac effects and clinical implications. PMID- 8000775 TI - The nurse's role in school-based mental health promotion: easing the transition into adolescence. AB - The developmental phase of adolescence is a critical transition that can be influenced by many factors. The author identifies some of the significant mental health problems for the "high-risk" adolescent. The importance of the Student Assistance Program and the role that the psychiatric/mental health nurse specialist plays in the context of this program are reviewed. PMID- 8000776 TI - Beliefs held by parents of autistic children. AB - Autism is an unusual disorder that offers varied and complex challenges. Recent shifts in educational and treatment foci have left many parents of autistic children floundering regarding how best to view and interact with their children. Furthermore, it has become clinically evident that these parents often maintain beliefs that may influence parent-child interactions and even the prognoses of the children. To date, no published research exists that examines how parental beliefs may affect autistic children. The author's purpose is to identify several common beliefs held by parents of autistic children and discuss implications for clinical practice and research. PMID- 8000777 TI - The psychological status of children with cancer. AB - The psychological and social functioning of a sample of 16 children with cancer was assessed 3-5 years after diagnosis using Achenbach's Child Behavior Checklist. Analysis indicated that 81% of the children were involved in age appropriate social interactions and the same percentage showed normal behavioral patterns. No significant differences were found due to gender, type of tumor, or behavior over time. The children in this sample appeared to be functioning normally, both psychologically and socially, three to five years after a diagnosis of cancer. PMID- 8000778 TI - Attention-deficit hyperactivity disorder--etiology, diagnosis, and management. AB - Attention deficit hyperactivity disorder is a developmentally disabling disorder of inattention, impulsivity, and hyperactivity that affects 3%-20% of school-aged children. It affects the child at home, at school, and with peers, and persists into adolescence and young adulthood. The author reviews the diagnostic criteria, etiological considerations, evaluation process, and management of this handicapping disorder. Included is a discussion of the most frequently used medications and suggestions for home and classroom management strategies that assist the child to behave and achieve success in school. It is pertinent to all nurses, since children with ADHD are in all settings and nurses are often asked questions about this controversial health care issue in both professional and personal arenas. PMID- 8000779 TI - It's about money and control. PMID- 8000780 TI - Nursing leaders speak out on HIV second decade of the pandemic. PMID- 8000782 TI - Position paper on foster care reform. PMID- 8000781 TI - Taming the tendency toward trend trumpeting. PMID- 8000783 TI - A look at adolescent treatment in a time of change. AB - Multiple changes in the authors' inpatient adolescent unit--including unit mergers, increased patient acuity, and shorter length of stay--created the need and opportunity to implement a new Behavioral Milieu Program with two significant components: A positive Behavioral Points System and 15 nurse-led groups. The authors describe this new program, which provides a safe and effective treatment modality and promotes each adolescent's sense of responsibility for his own behavior and life. Dramatic outcomes include decreased use of mechanical restraints by 56% in the first three months of implementation and by 82% in the second three months. This program has applications for inpatient units, community residences, and schools, and can even be adapted for home use by parents. PMID- 8000784 TI - [Neutrophil chemiluminescence using the Luminometer-1251 device and the Lumograf program]. AB - Luminometer-1251 device in complex with the IBM-PC type computer was used to record the neutrophilic chemiluminescence response. Luminol-dependent chemiluminescent response of human neutrophils treated with phorbol-12-myristate 13-acetate in concentrations from 0.5 to 100 nM was examined over a 5 h incubation period. The results were computer-processed using an authors' program Lumograf. The suggested method may be used to record and process the data of long coursing processes of chemiluminescence in a large series of samples. PMID- 8000785 TI - [Micro-determination of the intensity of luminol-dependent chemiluminescence of plasma]. AB - The authors attempted to modify the macro-method for assessment of the intensity of luminol-dependent chemiluminescence by using small volumes of capillary blood, diluted 100-fold. They have demonstrated the compatibility of two methods for blood collection, from the vein and from the finger, on the basis of the rapid test of oxygen intoxication severity and individual sensitivity of the body to hyperoxia in vitro. Use of microvolumes of the sample for analysis will facilitate the clinical application of the test for the selection of the optimal HBO schemes. PMID- 8000786 TI - [Quantitative assessment of deformation characteristics of biological cell membranes during filtration]. PMID- 8000788 TI - [Diagnostic significance of bone marrow examination. 2]. AB - Presents indications for bone marrow analysis, specific features of myelogram assessment, data on changes in myelograms in some diseases, interpretation of bone marrow indexes and some other parameters detected by bone marrow analysis, discusses auxiliary methods for such analysis. Necessitates the creation of a data bank for clinical, instrumental and laboratory data that will promote a more reliable diagnosis and facilitate bone marrow analysis for laboratory physicians. PMID- 8000787 TI - [Prognostic significance of the NBT test in patients with ichterohaemorrhagic leptospirosis]. AB - The values of spontaneous NBT test significantly rise at the peak of leptospirosis in patients with an uncomplicated course of the disease (p < 0.05). Low values of the spontaneous NBT test with stimulation with Staphylococcus in patients with grave leptospirosis predict the development of life-threatening complications. Leptospirosis vaccine reduced the elevated values of the NBT in leptospirosis. The depressing effect of leptospirosis vaccine is indicative of a high risk of development of late complications. PMID- 8000789 TI - [Biochemical factors of coronary atherosclerosis risk]. PMID- 8000790 TI - [Enzyme diagnosis of liver dysfunction in acute myocardial infarct and its complications]. AB - A complex of enzymatic tests, characterizing the liver function and cellular cytolysis in patients with acute myocardial infarction of various severities (without complications and with various types of complications and outcomes) was used in examinations over the first week of the disease. Significant changes in five of the seven tested enzymes were found: aspartate aminotransferase, glutamate dehydrogenase, sorbitol dehydrogenase, cholinesterase, alanine aminotransferase, the degree and incidence of changes in their activities being the lowest in the patients with acute myocardial infarction without complications, higher in those with this condition with isolated complications, still higher in those with combined complications and a favorable outcome, and the highest in those with combined complications and a lethal outcome. Secondary hepatopathy in patients with acute myocardial infarction augments as the complications develop, particularly in arrhythmia, disordered conductivity, and combined complications. Measurements of glutamate dehydrogenase and sorbitol dehydrogenase are recommended starting from the first day of the disease, of cholinesterase from the third day of the disease for a dynamic monitoring of the liver status in order to timely detect and correct hepatopathy and assess the status of patients with complicated acute myocardial infarction. PMID- 8000791 TI - [Laboratory diagnosis of preleukemia (review of the literature)]. PMID- 8000792 TI - [Monooxygenase system of the liver in chronic hepatitis according to the data of the antipyrine test]. AB - The activity of liver monoxygenase system was studied in 94 children with various clinical forms, activities and duration of chronic hepatitis by the antipyrine test and the diagnostic and prognostic significance of this test was assessed. The test is recommended for the assessment of the liver process severity and for the prediction of the disease course in children. PMID- 8000793 TI - [Determination of free and bound forms of sialic acids in biologic objects]. AB - A method for simultaneous measurements of free, oligomer-bound and protein-bound sialic acids in the blood serum, saliva, and tissue homogenates is offered. The results of these parameters measurements after stressogenic exposures and in some diseases are presented. PMID- 8000794 TI - [Laboratory tests in the diagnosis of stomach cancer]. AB - Blood alpha-fetoprotein, carcinoembyronic antigen, CA-19-9, alkaline phosphatase, gamma-glutamyltranspeptidase, alanine aminotransferase, aspartate aminotransferase, sorbitol dehydrogenase, glutamate dehydrogenase, hemoglobin and red cell sedimentation rate were measured in patients with stages III and IV gastric carcinoma and patients with benign diseases of the stomach. Alanine aminotransferase, sorbitol dehydrogenase and glutamate dehydrogenase were found diagnostically not informative in gastric carcinoma stages III and IV. A complex of measurements of alpha-fetoprotein, alkaline phosphatase, gamma-glutamyl transpeptidase and aspartate aminotransferase detected gastric carcinoma metastases to the liver in 84.6% of cases as against 61.5% detected by measurements of alpha-fetoprotein alone. A complex of measurements of carcinoembryonic antigen, CA-19-9, alkaline phosphatase, gamma-glutamyl transpeptidase, aspartate aminotransferase helped differentiate between gastric carcinoma stages III and IV. A complex of measurements of carcinoembryonic antigen, CA-19-9, alkaline phosphatase, gamma-glutamyl transpeptidase, aspartate aminotransferase, hemoglobin, and red cell sedimentation rate improved the diagnostic sensitivity in detection of gastric carcinoma stages III and IV to 70.8 and 100%, respectively. PMID- 8000795 TI - [Determination of prostaglandin contents in gastric juice]. AB - Gastric juice prostacyclin and thromboxane were radioimmunoassayed in patients with chronic gastritis and peptic ulcer and in normal subjects. Prostanoid secretion into the gastric lumen was found to reflect the degree of inflammatory changes in the gastric mucosa. PMID- 8000796 TI - [Method of the assessment of neutrophilic leukocyte and monocyte interactions in a mixed cell culture]. AB - The author offers a test system for studies of the interactions of agglutinating polymorphonuclear cells and neutrophilic leukocytes of human blood in a mixed cell culture. This method has demonstrated a modulation of the structural and functional status of the interacting cells. The counts of polymorphonuclear cells, expressing HLA-DR antigens, and of neutrophilic leukocytes with receptors to Fc fragment of IgG grow in the course of cell cultivation, and a number of cytokines, interleukin-1 and factors of chemotaxis of polymorphonuclear cells and neutrophilic leukocytes, are produced. PMID- 8000797 TI - [Evaluation of the state of systemic and local cellular immunity using loading tests]. AB - Local and systemic cellular immunity parameters of the blood and gastrointestinal mucosa were studied in 165 children suffering from chronic gastritis, duodenitis, celiac, secondary malabsorption syndrome, and phosphate diabetes by spontaneous E RFC method with a number of loading tests in vitro. Thymalin, theophylline, cold incubation were used. Three types of T lymphocyte response were distinguished: the hypoergic, resistant, and hyperergic. To make the interpretation of the findings easier, coefficients were calculated for each type of response of the blood and gastrointestinal mucosa immunocompetent cells. PMID- 8000799 TI - [Use of the peroxidase-antiperoxidase method in the determination of cellular antigens on cryostat sections using IKO series monoclonal antibodies]. AB - Presents the peroxidase-antiperoxidase method for the detection of cellular antigens on cryostate sections of various tissues, making use of the IKO monoclonal antibodies. Analyzes the possible errors and causes of potential artefacts. Describes the results obtained with the use of this method in examinations of the sections of malignant and benign tumors of the mammary gland and regional lymph nodes. PMID- 8000798 TI - [Determination of antibody avidity using passive hemagglutination reaction]. AB - The antibody avidity index is suggested for the assessment of antibody avidity, that is calculated according to the formula: (T4:T56) x (T4:T37) x (T4:T21), where Tn is the reverse value of antibody titer in the passive hemagglutination test with the same serum at various incubation temperatures. The interpretation of various values of the index is explained, both for the determination of antibody avidity level and for the diagnosis of infectious diseases. PMID- 8000800 TI - [Assessment of the informative value of cellular immunity parameters in persons with tobacco dependence]. PMID- 8000801 TI - [Immunoturbidimetric micromethod for measurement of serum immunoglobulins A and M using FP-900 analyzer]. PMID- 8000802 TI - [Bacteriological studies of intestinal microflora of the risk-group pregnant women]. AB - Bacteriologic studies of the large intestine microflora were carried out in pregnant women whose future newborns were at risk of developing infectious inflammatory diseases. The studies permitted the authors to determine not only the species and quantitative composition of the microflora, but to assess the degree of the dysbiotic disturbances and therefore the risk of dysbacteriosis development in the future infants. PMID- 8000803 TI - [Method of determination of Salmonella and Yersinia antigens adsorbed on on the surface of erythrocytes of the patients]. AB - The method is based on the fact that patients' red cells with the specific antigens adsorbed on their surface, interacting with the specific antibodies, enter the hemagglutination reaction. 8% red cell suspension with diluted commercial sera hyperimmune to Salmonellae and Yersinia, serovars O3 and O9, are used in the test. The hemagglutination test was found sufficiently specific and sensitive for the detection of even the lowest concentrations of the specific antigen on the surface of red cell membranes in the patients with salmonellosis and yersiniosis. PMID- 8000805 TI - [Development of a method for assessment of viability of Bifidobacterium in bificol]. PMID- 8000804 TI - [Evaluation of the severity of endogenous intoxication in obstetric sepsis]. PMID- 8000806 TI - [Micromethod of the determination of blood bactericidal activity in children]. PMID- 8000807 TI - [Erythroclastic bone marrow clusters and prognostication of the character of the course of acute lymphoblastic leukemia]. AB - A new variety of bone marrow clusters was revealed, that is formed of mature red cells by bone-marrow macrophages and other myelokaryocytes containing hydrolytic enzymes. Exocytotic lysis of the red cells, contained in these clusters, by cluster-forming cells is frequently observed. This fact permitted calling this variety 'erythroclastic clusters'. The number of clusters, in which exocytotic red cell lysis occurs, was found to grow fourfold in the active phase of acute lymphoblastic leukemia; this fact may be used for the early diagnosis of the disease or for prediction of its recurrence. PMID- 8000808 TI - BASM and the recognition of 'sports medicine'. PMID- 8000809 TI - Massage--the scientific basis of an ancient art: Part 1. The techniques. AB - Manual massage is a long established and effective therapy used for the relief of pain, swelling, muscle spasm and restricted movement. Latterly, various mechanical methods have appeared to complement the traditional manual techniques. Both manual and mechanical techniques are described systematically, together with a review of indications for use in sports medicine. PMID- 8000810 TI - Massage--the scientific basis of an ancient art: Part 2. Physiological and therapeutic effects. AB - The physiological and therapeutic effects of massage are frequently questioned. This article reviews previous research into the effects of massage on blood flow and composition, oedema, connective tissue, muscle and the nervous system. Although further investigations are clearly required in certain areas, the discussion demonstrates that the use of massage in sports medicine can be justified according to orthodox scientific criteria. PMID- 8000811 TI - Body composition of athletes in Bahrain. AB - A total sample of 304 athletes was selected from first class clubs related to four common sports (football, handball, volleyball and basketball) and compared with 53 non-athlete adults. Weight, height, mid-arm circumference and skinfold thickness were measured to assess their body composition. The findings revealed that there were differences in body composition among athletes according to the type of sport. Basketballers and volleyballers were the tallest athletes, while handballers were the heaviest ones. Skinfold thickness measurements showed that basketball and handball players have more subcutaneous fat than other athletic groups. As compared with non-athletes, the Bahraini players had higher means for height, weight, subscapular, suprailliac thickness and mid-arm circumference. PMID- 8000812 TI - Social-psychological predictors of self-reported actual and intended physical activity in a university workforce sample. AB - This study investigated the social-psychological predictors of self-reported actual and intended physical activity in a university workforce sample. Based on the 'Theory of Planned Behaviour', but with additional variables of benefits, barriers and self-efficacy, it was found that both intended and actual activity could be predicted but only when strenuous activity was considered. In addition, the predictors were different for men and women. Specifically, the best predictors of intention to exercise were attitude, perceived control, benefits and self-efficacy for women, but only attitude for men. Predicting self-reported strenuous activity for women were intention and self-efficacy, and for men intention and attitude. Theoretical and practical implications for attitude research and exercise promotion are discussed. PMID- 8000813 TI - Resistance exercise decreases beta-endorphin immunoreactivity. AB - Previous research investigating the response of plasma beta-endorphins (beta-EP) to resistance exercise has resulted in equivocal findings. To examine further the effects of resistance exercise on beta-EP immunoreactivity, 10 male and 10 female college-age students participated in a series of controlled isotonic resistance exercises. The session consisted of three sets of eight repetitions at 80% of one repetition maximum (1-RM) for each of the following exercises: (1) bench press; (2) lateral pull-downs; (3) seated arm curls; and (4) military press. Blood plasma was sampled both before and after the lifting routine and beta-endorphin levels were determined by radioimmunoassay. A Students t test for paired samples indicated that mean(s.e.) plasma beta-endorphin levels after exercise (10.5(1.3) pg beta-EP ml-1) were significantly decreased as compared with pre-exercise (control) levels (16.5(1.2), P < 0.05). While the mechanism(s) contributing to the decrease in immunoreactivity is unclear, it may be the result of the synergistic effect of beta-EP clearance during rest intervals and changes in psychological states between sampling. PMID- 8000814 TI - Time-of-day dependence of isokinetic leg strength and associated interday variability. AB - The purpose of this study was to assess the interday variability and time-of-day effects on selected isokinetic leg strength indices. Nine adult collegiate sportsmen (mean(s.e.) age 19.6(0.5) years; mean(s.e.) height 1.81(0.02) m; mean(s.e.) body mass 76.5(3.1) kg) completed a series of nine test sessions, organized so that each subject was tested three times within a day (08.00-09.00 hours; 13.00-14.00 hours; 18.00-19.30 hours), on three occasions, each separated by a minimum of 7 days. Gravity-corrected indices of extension peak torque (EPT), flexion peak torque (FPT), and the peak torque ratio (PTR), at contraction velocities of 1.05 rad s-1 and 3.14 rad s-1, were calculated for each subject using an isokinetic dynamometer. Two-way repeated measures analysis of variance of coefficient of variation (V%) scores revealed no significant differences in performance variability across within-subject factors of time-of-day and performance index (P > 0.05). Overall mean(s.e.) V% for scores across experimental conditions were 3.97(0.72)% at 1.05 rad s-1 and 5.98(1.23)% at 3.14 rad s-1, suggesting that similar levels of measurement error occur between 08.00 19.30 hours. One-way repeated measures analysis of variance of absolute strength indices (EPT, FPT and PTR) revealed that significantly higher scores were achieved during session 3 (18.00-19.30 hours), with mean(s.e.) values of 249.1(40.0) N m, 149.0(32.3) N m, 59.5(5.0)% at 1.05 rad s-1, and 172.1(38.7) N m, 121.3(27.7) N m, 71.1(6.2)% at 3.14 rad s-1, respectively (P < 0.05). This finding appears to be consistent with current knowledge about time-of-day effects on the assessment of muscular strength. Thus for stable and maximal values to be obtained during isokinetic leg testing, the use of multiple-trial protocols is recommended, with testing occurring as close to 18.00-19.30 hours as possible. In addition, the observed significant time-of-day effect suggests that appropriate comparison of maximal isokinetic leg strength can only be achieved based on data obtained within 30 min of the same time of day. PMID- 8000815 TI - The influence of dietary carbohydrate and pre-exercise glucose consumption on supramaximal intermittent exercise performance. AB - The present study examined whether a pre-exercise consumption of glucose by subjects having adhered to a 3-day low carbohydrate (CHO) or normal CHO diet would influence supramaximal intermittent exercise performance. Sixteen moderately active men volunteers (mean(s.d.) age 20.0(1.3) years) agreed to undertake three exercise tests over an 8-day period; in addition to completing a VO2max test, the subjects performed two identical maximal interval tests (MIT1 and MIT2). Periods of 3 days separated each of the three tests. The interval tests involved five 60-s 'all-out' cycling bouts working against a resistance of 0.075 kg kg-1 body mass; each bout was separated by 5 min of passive recovery. For 3 days preceding the first interval test (MIT1), all subjects adhered to a 'moderate' CHO diet which comprised 59.1% (approximately 4.1 g kg-1 body mass) of the daily energy intake as CHO. Following MIT1 and for 3 days before MIT2 subjects were randomly assigned to follow either a moderate CHO diet (60.8%) or a low CHO diet (14.4% or 1.1 g kg-1 body mass). All food and drink consumed during the experimental period was weighed and recorded for later dietary analysis. One hour before MIT2, eight subjects were administered (in single blind fashion) a 15% glucose solution (1 g kg-1 body mass) while the other eight subjects consumed a low-energy sweetened placebo. During both interval tests, values of work, exercise VO2, plasma glucose, plasma lactate and venous blood pH were statistically analysed. No changes in performance between MIT1 and MIT2 across conditions were found (P > 0.05). However, those subjects who consumed the glucose solution before MIT2 (irrespective of their dietary CHO intake) consumed significantly less oxygen during exercise than those who had been given the placebo solution (P<0.05). While these findings question the ergogenic potential of consuming glucose before supramaximal exercise, the VO(2) data implicate a possible shift in substrate utilization during repeated sprint exercise after pre exercise glucose ingestion. PMID- 8000816 TI - Prevalence of latent and manifest suprascapular neuropathy in high-performance volleyball players. AB - The aim of the present study was to evaluate the prevalence of latent and manifest suprascapular neuropathy in high-level male volleyball players. Thirty subjects were examined clinically and electrophysiologically. Suprascapular neuropathy, most probably at the level of the suprascapular notch, was demonstrated in 12 subjects, being latent in eight. Taking into account our clinical findings in a further 36 international-level players, a remarkably high overall prevalence of suprascapular nerve lesion of 33% (22 of 66 subjects) was found. All cases involved the side of the body with the player's smashing arm. These findings suggest that careful monitoring of suprascapular nerve function may be useful in high-performance volleyball players, as early diagnosis is essential to prevent more severe damage. PMID- 8000817 TI - The scientific basis for the use of biomechanical foot orthoses in the treatment of lower limb sports injuries--a review of the literature. AB - While it is documented that many overuse injuries of the lower limb can be relieved with the use of biomechanical foot orthoses, what remains unclear is how an orthosis can produce this effect. A review of the literature indicates that biomechanical orthoses will reduce rearfoot movement, but the effect on knee function is negligible and the clinical significance of excessive rearfoot movement is yet to be proven. While many athletes may potentially benefit from the use of biomechanical orthoses, further research is necessary to justify and, if indicated, promote the use of biomechanical foot arthoses by athletes suffering from overuse injuries. PMID- 8000818 TI - Radiographic changes in the hands of rock climbers. AB - Radiographs of the hands of 36 rock climbers were compared with radiographs of the hands of controls matched for age and sex. Subchondral cysts were present in the hands of 17 climbers and only two controls. Osteophytes or bony spurs were present in 14 climbers but not in any of the controls, and the only two cases of frank osteoarthrosis were in the hands of climbers. Cortical thickness of the proximal and middle phalanges was significantly greater in the hands of climbers (P = < 0.01). Pronounced 'scalloping' of the necks of the proximal phalanges was only seen in climbers, and is due to thickening of the attachment of the distal end of the fibrous A2 pulley of the flexor sheath. PMID- 8000820 TI - An epidemiological investigation of training and injury patterns in British triathletes. AB - During the competitive season of 1990, 155 British triathletes whose competitive distances varied from sprint to full ironman, and who self-classified themselves as recreational, intermediate or elite, kept a training diary for an 8-week period. They gave details of injuries sustained while training for, or competing in, triathlons. The mean(s.d.) distances covered each week were: swimming, 4.2(2.6) km; cycling, 100.2(70.6) km; and running 23.4(15.2) km; mean(s.d.) training time was 7(3.4) h per week, and a mean(s.d.) of 7.9(3.4) training sessions were completed per week. At least one injury was reported by 37% of the participants. The most frequently affected sites were the ankle/foot, thigh, knee, lower leg and the back. Overuse was the reported cause in 41% of the injuries, two-thirds of which occurred during running. The likelihood of an injury was positively associated with experience in triathlon. Average injury rate was 5.4 injuries per 1000 h of training (95% confidence interval: 4-7.2) and 17.4 per 1000 h of competition (95% confidence interval: 10.9-27.9). Injury incidence was unrelated to the mean amount of weekly training or competition, intensity or frequency of training. PMID- 8000819 TI - Neuropsychological investigation of amateur boxers. AB - Amateur boxing is faced with criticism over the potential damage the sport inflicts on those who participate. The most sensitive measure of early neurological dysfunction is neuropsychological investigation. Ten studies employing such assessments on 289 amateur boxers are reviewed. The forms of analysis undertaken include controlled comparison with other sportsmen, of both active and former boxers, detailed pre- and post-bout analysis, analysis of the influence of within-boxing variables, length of career, level of competition and prospective longitudinal investigation. Amateur boxers were found to exhibit no signs of neuropsychological dysfunction in any analysis. However some trends emerged suggesting a long career in amateur boxing might reduce fine motor reactions, although such findings are within the normal range and do not represent central neuropsychological functioning. Thus amateur boxing does not appear to expose individuals to neurological dysfunction. PMID- 8000821 TI - Track and field athletics injuries--a one-year survey. AB - The training programmes and competitive performances of 147 track and field athletes, from many different clubs within the UK, were analysed retrospectively in order to study the incidence, severity and types of injuries which they had suffered during the year September 1989-September 1990. This information was then related to the particular event in which they specialized as well as a number of hypothetical risk factors proposed for making them more prone to injury. Of the athletes 96 (65.3%) were male and 51 (34.7%) were female, and their ages ranged from 14 to 32 years, with their levels of competition ranging from 'competitive spectators' to UK internationals. A marked correlation was noted between their age, level of competition, number of supervised training sessions which they attended, and their incidence of injuries. However, certain other factors which were studied, such as their sex, the hours they trained, and the particular event in which they specialized appeared to provide no obvious relationship. PMID- 8000822 TI - Femoral osteochondral fracture--a non-contact injury in martial arts? A case report. AB - A report of a case of osteochondral fracture of the lateral femoral condyle in a patient doing a karate kick. The problems related to fixation of osteochondral fragments with protruding screws are highlighted and the suitability of Herbert screw fixation noted. PMID- 8000823 TI - Case report--stress fracture of the rib in a golfer. PMID- 8000824 TI - A proposed figure of merit for the assessment of unscheduled treatment interruptions. AB - There are, as yet, no standard radiobiological methods for devising compensation for unscheduled interruptions to fractionated radiotherapy. For the foreseeable future it is likely that the concept of biologically effective dose (BED) will play an important role in the intercomparison of treatment regimes, and in the examination of the options available for dealing with unscheduled treatment interruptions. However, comparison of the BEDs associated with different treatment options does not provide an intuitively obvious indication of the magnitude of any associated differences in biological effect--an important consideration in the case of those treatments which are designed to deliver near tolerance doses. This article reviews the implications which derive from this complication, and discusses the desirable properties of possible "one-number" treatment scoring systems which could utilize the BEDs of both the tumour and the critical normal tissue. One possible form of such a scoring parameter is suggested, and applied to some clinical examples. No special "robustness" is claimed for the proposed scoring system, but the method nevertheless allows the ranking of treatment options such that the least satisfactory may be identified and rejected. PMID- 8000825 TI - Cell survival measurements in an argon, aluminium and sulphur filtered neutron beam: a comparison with 24 keV neutrons and relevance to boron neutron capture therapy. AB - Boron neutron capture therapy (BNCT) has been advanced as a suitable alternative therapy for the treatment of glioma. BNCT involves the selective uptake of a tumour with a boron-bearing substance and subsequent irradiation with a beam of neutrons. Previous attempts with BNCT have utilized thermal neutrons, but this involves resection of the scalp prior to treatment and is only possible with superficial tumours. An alternative is to use a beam of intermediate-energy neutrons which will produce a peak in the thermal neutron fluence at depth in tissue and so enable deep-seated tumours to be treated. A neutron beam with a mean energy of approximately 9 keV, obtained by filtering neutrons from a reactor with aluminium, argon and sulphur, has been used to explore the radiobiological advantage over thermal and 24 keV neutrons for BNCT. Irradiation of V79 and HeLa cells at various positions in a polythene phantom suggest that the beam is less cytotoxic for a given neutron fluence than the 24 keV neutron beam previously considered as an alternative to thermal neutrons for BNCT. However, optimization of boron distribution via the development of new compounds still appears to be necessary for BNCT to become a safe alternative option for the treatment of glioma. PMID- 8000826 TI - Technical note: dosimetry in the moving gap region in craniospinal irradiation. AB - To minimize the risk of overlap of adjoining orthogonal fields in craniospinal irradiation, a skin gap is usually maintained between the caudal margin of the brain fields and the cephalic margin of the spine field. The moving gap technique (feathering) is commonly used to improve the dose in the gap region. Using Kodak XV ready-pack films and a polystyrene phantom, the dosimetry in the moving gap region at the depth of spinal cord for different gap sizes and feathering step sizes was studied. The dose profiles in the moving gap region with half-beam block set-up were also measured. Our results show that the combination of a small skin gap and a larger feathering step size results in a higher dose in the moving gap compared with that with identical gap and feathering step sizes. For example, with a 0.5 cm gap and 1 cm feathering step size, the dose in the moving gap region at depth of 5 cm ranges from 82 to 88% of the dose to the brain field. The corresponding dose range with 1 cm gap and 1 cm feathering step size is about 68 73%. With no gap and 1 cm feathering step, a dose range of 92-98% is achieved in the moving gap. The slightly steeper penumbra of a half-beam block used in the brain fields does not result in any dosimetric advantage in the moving gap compared with the conventional set-up when feathering is employed. PMID- 8000827 TI - Case report: sicca syndrome due to primary amyloidosis. AB - Sicca syndrome consists of two major clinical findings: keratoconjunctivitis sicca and xerostomia due to destruction of the lacrimal and salivary gland parenchyma. Although it is most often due to Sjogren's syndrome, a variety of other diseases causes sicca syndrome. We report the rare case of a patient with gland infiltration in primary amyloidosis. Sonographic, computed tomographic and magnetic resonance findings are presented. PMID- 8000828 TI - Case report: perinephric angiomyolipomas in tuberous sclerosis. AB - Bilateral large perinephric angiomyolipomas in a young Chinese woman with tuberous sclerosis are reported. Computed tomography (CT) demonstrated large fatty masses, containing abnormally dilated blood vessels and muscle strands, within the Gerota's fascia bilaterally. There were multiple foci of involvement in both kidneys. The diagnosis was confirmed on histological examination of the excised left perinephric angiomyolipoma and nephrectomy specimens. The patient subsequently developed bilateral pneumothoraces which were surgically treated. High resolution CT showed extensive thin-walled cysts in both lungs. PMID- 8000829 TI - Case report: uptake of pentavalent technetium-99m dimercaptosuccinic acid by pigmented villonodular synovitis: comparison with computed tomography, magnetic resonance imaging and gallium-67 scintigraphy. AB - The scintigraphic findings of a patient with pigmented villonodular synovitis are described and compared with the computed tomography and magnetic resonance imaging data. Intense uptake of pentavalent technetium-99m dimercaptosuccinic acid without gallium-67 citrate uptake indicates that pigmented villonodular synovitis has the features of a hyperplastic or neoplastic lesion rather than an inflammatory lesion from the point of view of nuclear medicine. PMID- 8000830 TI - Case of the month: "but fell like autumn fruit that mellowed long" (John Dryden). PMID- 8000831 TI - Outcome of 249 patients attending a nuclear medicine department with well differentiated thyroid cancer; a 23 year review. PMID- 8000832 TI - Imaging studies for emphysematous pyelonephritis. PMID- 8000833 TI - European Society of Mastology Consensus Conference on breast cancer screening: report of the evaluation committee. AB - On 4 February 1993, the European Society of Mastology (EUSOMA) convened a meeting of experts in Paris to evaluate the current evidence on the value and hazards of breast cancer screening. The Committee consisted of individuals from different countries throughout Europe and from different disciplines. We summarise here the deliberations and conclusions of the Committee. PMID- 8000834 TI - Knee effusions, radiology and acute knee trauma. AB - Sixty patients with acute knee trauma were examined radiographically at presentation and subsequently examined under anaesthetic, when arthroscopy was performed. The aim was to assess whether a normal radiograph at presentation excluded significant knee pathology. Nine patients with significant pathology (25%) had normal radiographs at presentation. PMID- 8000835 TI - Computerized strain-gauge plethysmography in the diagnosis of symptomatic and asymptomatic venous thrombosis. AB - This study compares the results of a computerized strain-gauge plethysmograph with ascending lower limb venography in 94 patients with clinical deep venous thrombosis, and in 121 patients with asymptomatic legs being screened after total hip replacement. In the symptomatic patients, strain-gauge plethysmography had a sensitivity of 100%, an accuracy of 73%, a specificity of 64% and a negative predictive value of 100% for thrombosis above the popliteal confluence. In the screened patients, the figures were 38.1%, 55.4%, 60.0% and 81.1% respectively. Computerized strain-gauge plethysmography is a safe, non-invasive, reliable and portable method of excluding proximal thrombosis in a symptomatic patient. It avoids the need for urgent venography when anticoagulation therapy is reserved for those with proximal thrombosis. The device was not valuable as a screening tool after total hip replacement, since it had a low specificity and did not reliably detect the non-occlusive mural femoral thrombi which typically follow this procedure. PMID- 8000836 TI - A comparison of a conventional non-ionic contrast medium (iohexol) alone and with adrenaline and an iso-osmolar non-ionic contrast medium (iotrolan) in computed tomographic arthrography of the shoulder. AB - The physico-chemical properties of the iso-osmolar dimeric contrast medium iotrolan offers potential advantages in computed tomographic arthrography (CTA). A trial was undertaken comparing iotrolan with iohexol to assess if these theoretical benefits produced an increase in the measured densities in a series of shoulder CTAs. The results showed that iotrolan did produce clinically useful increases in density when compared to a monomeric non-ionic contrast medium. The addition of adrenaline to the monomeric contrast medium produced a significant improvement in the computed tomography density which surpassed that offered by the dimeric contrast medium alone. PMID- 8000837 TI - Reporting of fracture radiographs by radiographers: the impact of a training programme. AB - In order to determine what influence training would have on their ability to interpret skeletal radiographs from the accident and emergency department, a 6 months training programme was established for three radiographers in various aspects of the radiology of orthopaedics and skeletal trauma. During the study the radiographers reported on radiographs from the accident and emergency department and each month an evaluation of their accuracy was undertaken. The overall radiographer error rate for fracture detection (false positive and false negative) declined during the training period. This was highly significant (p < 0.001). The sensitivity for fracture detection improved from 81.1% at the commencement of the trial to 95.9% at the end. This was also highly significant (p < 0.001). Radiographer specificity for the exclusion of fractures also improved from 94.4% during the first 2 months to 96.6% in the final 2 months, and this was also significant (p < 0.05). The overall error rate of two of the three radiographers improved significantly (p < 0.001) but for one radiographer the improvement did not reach a level of statistical significance. The difference in sensitivity for fracture detection at the commencement of the trial period between radiologist and radiographer was highly significant (p < 0.001), but there was no statistically significant difference during the last two months of the trial. The difference in specificity between radiologist and radiographer remained highly significant both at the beginning and the end of the trial (p < 0.001). Experienced radiographers who receive supplementary training in the radiology of skeletal trauma can significantly improve their diagnostic skills and can report such radiographs with a high degree of accuracy. A programme of training and certification of radiographers in fracture reporting could help alleviate the diagnostic radiologists' workload of plain film reporting. PMID- 8000838 TI - The persistent computed tomography nephrogram: its significance in the diagnosis of contrast-associated nephrotoxicity. AB - A study was undertaken to find out if there is a quantitative relationship between the development of contrast-associated nephrotoxicity (CAN) and the mean renal cortical attenuation (RCA) as seen on computed tomography (CT) examination of the kidneys 24 hours after injection of contrast medium. 96 patients undergoing aortography were selected, who were considered "high risk" either because of the presence of a baseline serum creatinine (Cr) of 123.76 mumol l-1 (1.4 mg dl-1) or higher, or who were 73 or older with or without elevated creatinine levels. A CT study of the kidneys at approximately 24 h was correlated with baseline serum creatinine as well as 24 h Cr (48-72 h Cr when available). Medical history and medications were recorded. Eight of 96 patients had RCA of 108-236 HU at 24 h CT and all developed significant CAN of varying degree; 3/96 had RCA ranging from 48 to 67 HU and had transient CAN; two other patients with RCA of 67-90 HU developed CAN; and there was increased incidence of CAN in patients: (a) with pre-existing renal insufficiency; (b) with diabetes with renal insufficiency; (c) on diuretics; (d) who were older; and (e) had a unilateral atrophic kidney. It was concluded that a 24 h CT study evaluating the RCA had better predictive value for the development of CAN than a 24 h creatinine level. PMID- 8000839 TI - Iomeprol versus iopromide for intravenous urography. AB - Iomeprol (B16880) is a new non-ionic tri-iodinated radiographic contrast medium. It was the aim of this double blind randomized phase III clinical trial to compare the local and systemic tolerance of iomeprol-300 (300 mg I ml-1) with the commercially available iopromide-300 (300 mg I ml-1) in a group of 198 patients needing intravenous urography. The contrast medium was injected rapidly into an antecubital vein within 2-3 min in most cases, using a standard dosage of 1 ml kg 1 body weight. The proportion of patients with an allergic diathesis was 25% in the iomeprol group and 17.3% in the iopromide group. There were no life threatening adverse reactions. Eight patients (8%) receiving iomeprol and 6 (6.1%) receiving iopromide had a sensation of heat related to the injection of contrast medium. Only one patient (1%) in the iomeprol group and two patients (2%) in the iopromide group noted pain on injection. Although the incidence of all other side-effects was relatively high (7% after iomeprol and 11.2% after iopromide) these reactions were generally harmless. The most common symptom was nausea and/or vomiting, which occurred with the same incidence (5%) in both groups. Only one patient in each group developed urticaria or erythema. Vital parameters remained essentially unchanged in all patients. The results suggest that iomeprol is a safe contrast medium, with a tendency to produce fewer side effects than iopromide, which is known to be particularly well tolerated. PMID- 8000840 TI - Technetium-99m hexamethylpropyleneamineoxime labelled leucocyte scanning in the initial diagnosis of Crohn's disease. AB - The technetium hexamethylpropyleneamineoxime labelled white cell scan (WCS) is not widely used as a screening test for Crohn's disease primarily because, though sensitive, it is perceived as being insufficiently specific. A series of 42 patients screened for Crohn's disease by this method was analysed retrospectively. The sensitivity was 100% and specificity 91%. This performance was maintained in a subgroup of these patients with very low prevalence of disease. If appropriate criteria for interpretation are used the WCS is a specific as well as a sensitive screening test for Crohn's disease. PMID- 8000841 TI - The relationship between bone mineral density, vertebral body shape and spinal curvature in the elderly thoracolumbar spine: an in vitro study. AB - Vertebral body geometry, defined by the anterior/posterior (A/P) and mid/posterior (M/P) vertebral body height ratios, was measured in 18 vertebral columns (T1-L5) from sagittal computed tomography scans. For each vertebra, the trabecular density (VTD) and bone mineral density (BMD) were measured using quantitative computed tomography (QCT) and dual-energy X-ray absorptiometry (DXA), respectively. Lateral view radiographs were digitized to measure the thoracic curvature. The segmental correlations between vertebral shape and bone density were poor (r = 0.01-0.31). The mean thoracic BMD and VTD and the mean lumbar VTD were significantly correlated with the mean thoracic A/P ratio (r = 0.55-0.69). The thoracic curvature was significantly correlated with both the mean thoracic and the mean lumbar VTD and BMD (r = 0.55-0.73). In summary, the extent of vertebral wedging and thoracic curvature was moderately indicative of the mean BMD of the thoracic vertebrae, and lumbar spine densitometry is useful to assess the relative severity of osteopenia in individuals with thoracic vertebral deformities. PMID- 8000842 TI - Magnetic resonance image synthesis using a flexible model. AB - Image synthesis methods are based on the hypothesis that a magnetic resonance (MR) image with optimized contrast can be reproduced by synthesis from three calculated basic images of T1, T2 and spin density. This method, however, is limited by noise due to uncertainties in the initial measurements. The principal component analysis (PCA) method is based on an information theory approach that decomposes MR images into a small set of characteristic feature images. PCA images, or eigenimages, show morphology by condensing the structural information from the source images. Eigenimages have also been shown to improve contrast-to noise ratio (CNR) compared with source images. In this study we have developed a method of synthesizing MR images using a flexible model, comprising a set of eigenimages derived from PCA. A matching process has been carried out to find the best fit between the model and a synthetic image calculated from the Bloch equations. The method has been applied to MR images obtained from a group of patients with intracranial lesions. The images derived from the flexible model show increased lesion conspicuity, reduced artefact and comparable CNR to the directly acquired images while maintaining the MR characteristic information for diagnosis. PMID- 8000844 TI - Physical evaluation of computed radiography as a mammographic X-ray imaging system. AB - The physical imaging properties of a computed radiography (CR) system operating under mammographic exposure conditions have been measured. These measurements include modulation transfer function (MTF), sensitometric response and noise power spectrum (NPS). These figures were used to derive signal-to-noise ratio (SNR) descriptors of the system performance. The same measures were derived for a mammographic film-screen system. The SNR properties of the CR system indicate superior low frequency performance over a wider dynamic range than the film screen system. The spatial frequency dependent SNR properties of the CR system are, however, limited. The results of a psychophysical test support the results obtained from physical measurements. These results indicate that despite its limited sharpness, details of dimensions relevant to diagnosis in mammography (circular details 0.25 mm diameter to represent microcalcifications and 3 mm diameter to represent small masses) are reproduced using CR with SNRs which are at least comparable with those of a mammographic film-screen system. PMID- 8000843 TI - The effects of static 3.0 T and 0.5 T magnetic fields and the echo-planar imaging experiment at 0.5 T on E. coli. AB - Various mutant strains of Escherichia coli have been exposed to a homogeneous static magnetic field of either 0.5 T or 3.0 T and to the time varying magnetic fields found in echo-planar imaging experiments. No evidence of increased DNA damage was detected, even with bacterial strains disabled for DNA repair. PMID- 8000845 TI - Patient radiation doses from enteroclysis examinations. AB - Data relating to patient dose have been acquired for enteroclysis examinations (small bowel enemas) performed at the John Radcliffe Hospital, Oxford, on 23 adult patients. Dose-area products, fluoroscopy times and the number of radiographs taken are used to compare the examination procedure at the John Radcliffe Hospital with enteroclysis and barium follow-throughs performed elsewhere. The mean dose-area product for the 23 examinations was 6.8 Gy cm2 and the mean effective dose was estimated to be 1.5 mSv. These doses are intermediate between those arising from barium meals and barium enemas performed in the same room. PMID- 8000846 TI - MHC antigens and haemopoiesis. PMID- 8000847 TI - Monoclonal antibodies in organ transplantation: an overview. PMID- 8000848 TI - Cytokine gene expression in human cardiac allograft recipients. AB - The long-term success of heart transplantation for end-stage heart disease has been hindered by the problems associated with acute and chronic graft rejection, opportunistic infections and potentially fatal complications of intensive immunosuppression. A more complete understanding of the biology of transplant rejection should provide the basis for the development of improved methods for controlling and monitoring rejection. Cytokines, the soluble factors which regulate the immune response, are central to the rejection process. The objective of this study was to analyse cytokine mRNA transcripts in 99 biopsy samples and 89 blood samples from 65 and 35 Stanford Medical Center cardiac transplant recipients, respectively, gathered between January 1990 and January 1992. Following RNA extraction and conversion to cDNA, samples were amplified with cytokine-specific primers for interleukins (IL) 1 to 8, TNF-beta (tumour necrosis factor-beta) and IFN-gamma (interferon-gamma) and were analysed by gel electrophoresis and Southern blot hybridization. Our results demonstrate that despite chronic immunosuppressive therapy, the peripheral blood of transplant recipients expressed a higher combined percentage of different cytokine transcripts than did peripheral blood obtained from normal volunteers. In transplant patients, detection of cytokine transcripts for IL-1 alpha, IL-1 beta and IL-2 increased with time after transplantation. Intragraft IL-7 gene expression was significantly increased in biopsies diagnosed with mild (grade 1) rejection when compared to those with no evidence of rejection or with moderate to severe rejection. Implications of these results in light of possible mechanisms of rejection and of new approaches to immunotherapy are discussed. PMID- 8000850 TI - T cell receptor (beta chain) transgenic mice have selective deficits in gamma delta T cell subpopulations. AB - TCR-beta (T cell receptor-beta chain) transgenic mice have altered lymphocyte development. TCR-beta transgenic mice are hyporesponsive to alloantigens in vivo and are deficient in gamma delta T cells. In order to begin a study of the relationship between a deficiency of alloreactive gamma delta cells and the defective function of in vivo alloantigen recognition, we analysed the gamma delta T cell development in TCR-beta mice. The presence of the TCR-V beta 8.2 chain transgene is associated with inhibition of gamma chain gene rearrangement. In order to determine how the presence of the TCR-beta transgene affects gamma delta T cell development, gamma delta T cells were studied in the skin, intestine and spleen. TCR-beta mice have dramatically reduced numbers of gamma delta T cells in the spleen and moderately reduced numbers of gamma delta T cells among intestinal intraepithelial lymphocytes. In contrast, these mice have normal numbers of gamma delta dendritic epidermal cells (DEC). These selective deficits could be due to the developmental regulation of transgene transcription during fetal life. We examined transcription of the TCR-beta transgene in the fetal thymus and found that the TCR-beta transgene is first transcribed at high levels on day 16 of fetal life, after DEC have already migrated from the thymus to the epidermis. Furthermore, mRNA from the transgene was detected in DEC, ruling out the formal possibility that DEC bear a gamma delta receptor only because they are incapable of expressing the transgene.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8000849 TI - Differential patterns of T cell clonal deletion in neonatal H-2 tolerance and I E/Mls induced self-tolerance. AB - The pattern of clonal deletion of putative I-E-reactive (V beta 11) and Mls reactive (V beta 3) T cells was evaluated and compared by cytofluorographic and immunohistochemical methods in a model of neonatal H-2 tolerance and in I-E- or Mls-bearing strains of mice which normally delete these cell populations (self tolerance). The ontogeny of deletion of V beta 11+ cells was studied by evaluating thymic changes from birth until maturity in B10.S (H-2s/I-E-), B10.A (H-2k/d/I-E+) and B10.S mice intravenously infused at birth with (B10.SxB10.A)F1 lymphohaematopoietic cells. The reduction in V beta 11+ cells was most prevalent in the medullary region of the naive B10.A and neonatally injected B10.S animals and was corroborated by flow cytometry which demonstrated a marked reduction in single CD4 and CD8 positive B beta 11 T cells when compared to naive B10.S mice. However, immunohistochemistry illustrated that 'deletion' was never complete since V beta 11+ cells remained in the thymic cortex and splenic lymphoid follicles. By comparison, DBA/2 mice (Mlsc+ and previously documented to have decreased levels of V beta 3+ cells) showed a different pattern of deletion of V beta 3+ T cells than what was found for T cells bearing V beta 11 in animals deleting this population. DBA/2 thymi contained fewer thymic V beta 3- cells and there was more complete elimination of these cells, particularly in the periphery, by flow cytometry and immunohistology. The mice which do not delete V beta 3 cells (Mlsc-) showed that the majority of V beta 3- cells were located in the medulla with a few cells distributed in the cortical region. This pattern was notably different than the distribution of V beta 11 cells in thymi. Despite their location by histology, the majority of remaining V beta 3+ cells were dual CD4/CD8 positive (CD4+CD8+) by flow cytometric analysis. Our data illustrate that V beta 11 and V beta 3 T cells appear to be eliminated (i.e. 'deleted') at similar stages of maturation (single positive) during self-tolerance as well as in a neonatal H-2 tolerance model. However, the degree of elimination and the location of the cells remaining in these mice is dramatically different, depending on which T cell population is being evaluated and which deleting ligand is presented intrathymically. Thus, the accepted tenet of dual CD4+CD8+ cells localizing to the thymic cortex appears to have exceptions.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8000851 TI - Xenotransplantation: an examination of the adhesive interactions between human lymphocytes and porcine renal epithelial cells. AB - Specific adhesion molecules stabilize the binding between lymphocytes and antigen bearing cells; this intercellular adhesion is vital to both the affector and effector phases of an immune response. It is not known whether adhesion molecules and their counter-receptors can form the cross-species interactions that will facilitate human T cell recognition of xenogeneic porcine target cells. In this report it is demonstrated that a higher proportion of mitogen-activated than of resting human lymphocytes adhere to cultured porcine renal epithelial cells. Furthermore, antibody blocking experiments demonstrated that at least part of this cell-cell binding is stabilized by the human adhesion molecules LFA-1 (lymphocyte function-associated antigen-1) and the alpha 4-containing integrins. It is possible that this capacity for cross-species adhesion will play a role during the cell-mediated rejection of clinical porcine xenografts. PMID- 8000852 TI - Preformed antibody and complement rebound after plasma exchange: analysis of immunoglobulin isotypes and effect of splenectomy. AB - Splenectomy (Sx) has been proposed to attenuate post-PE (plasma exchange) rebound of isoagglutinins and xenogenic (XG) antibody (Ab) in both ABO-incompatible allografts and discordant xenografts. This study analyses the qualitative nature and kinetics of serum immunoglobulins as well as complement resynthesis after PE in sham-operated (PE) and splenectomized (PE+Sx) syngeneic LOU/C rats; non-PE sham-operated or splenectomized animals were used as controls. PE was performed in unanesthetized, unheparinized rats. Immunoglobulin isotypes and subclasses (IgM, IgG1, IgG2 alpha, IgG2b) of total circulating Ab were measured pre-PE and up to 21 days post-PE, using ELISA (enzyme-linked immunosorbent assay) and specific mouse antirat monoclonal Ab. Antiguinea-pig (GP) XG Ab (IgM, IgG2a) serum levels were measured using cellular ELISA with cultured GP endothelial cells as targets. Sx alone significantly reduced XG IgM serum levels (p < 0.0001). Maximal rebound of total and XG IgM was observed on day 3 post-PE, reaching 674% and 187% of the pre-PE levels, respectively; these overshoots were entirely suppressed by Sx (p < 0.005 for total IgM; p < 0.0001 for XG IgM). Total IgG2a, IgG2b and IgG1 as well as XG IgG2a serum levels did not show significant overshoot post-PE. The activity of the complement classical pathway (mean +/- SD), assessed by CH50, was decreased at 51 +/- 19% of basal value 15 minutes after PE, and had returned to baseline level by day 2 post-PE with or without Sx. IN CONCLUSION: (1) Six alone significantly reduced XG IgM serum levels; (2) early post-PE Ab rebound was mainly observed for IgM; (3) both total and XG IgM rebound was inhibited by Sx. This suggests that Sx probably removes a significant proportion of IgM producing cells undergoing post-PE stimulation. These data provide a rationale for combining PE with Sx in ABO-incompatible and discordant XG transplantation. PMID- 8000853 TI - Effect of panel reactive antibody on live related donor kidney transplantation: Indian experience. AB - Serum samples from 95 recipients, transplanted with kidneys from live related donors, were tested for the presence of panel reactive antibodies (PRA) in pre- and post-transplant serum samples by the extended microdroplet lymphocytotoxicity test. The immunoglobulin class of antibodies was tested by treatment of serum with dithiothreitol. A significant correlation was found between the high PRA found in the 75 pretransplant sera tested and the subsequent rejection episodes. In addition, the level of pretransplant PRA activity was associated with graft survival in that patients with low PRA had significantly superior graft survival than those with high PRA. Furthermore, the present data show that patients with historical high PRA, but current low PRA, had graft survival similar to that in recipients who had moderate PRA in their current sera. High PRA patients had more often a positive crossmatch than patients with low PRA. The PRA level was also associated with prolonged waiting period. Immunoglobulin class of antibodies was related to graft acceptance in that the presence of IgM antibodies was not detrimental to transplantation. The results in the present study suggest that PRA of < 10% is negligible, while more attention should be paid to patients with PRA > 10%. PMID- 8000854 TI - Polymerase chain reaction detection of chimerism in rats based on an allelic polymorphism for T cell antigen receptor C beta genes. PMID- 8000855 TI - Thymocytes bearing high-density T cell receptor and CD2 are selectively eliminated in cyclosporine-induced thymic atrophy. PMID- 8000856 TI - Glyoxylic acid production using immobilized glycolate oxidase and catalase. AB - A variety of methods for the immobilization of glycolate oxidase have been examined for the preparation of a catalyst for the oxidation of glycolic acid to glyoxylic acid. The co-immobilization of glycolate oxidase and catalase on oxirane acrylic beads produced a catalyst which was stable to the reaction conditions used for the oxidation, where glycolic acid and oxygen are reacted in aqueous solution in the presence of the immobilized enzyme catalyst and ethylenediamine. Under optimum reaction conditions, 99% yields of glyoxylic acid were obtained at greater than 99% conversion of glycolic acid, and the recovery and reuse of the co-immobilized enzyme catalyst was demonstrated. PMID- 8000857 TI - Inactivation of D-3-hydroxybutyrate dehydrogenase by fumaroyl bis(methyl phosphate). AB - Fumaroyl bis(methyl phosphate) reacts with the NADH-dependent enzyme, D-3 hydroxybutyrate dehydrogenase, leading to irreversible inactivation. The bifunctional reagent cross-links the subunits of the enzyme. The inactivation is subject to saturation and protection by substrate, consistent with the reaction occurring at the active site. The stoichiometry of inactivation indicates two active sites undergo reaction with each equivalent of reagent. These results indicate that the dimeric enzyme has contiguous active sites. The reagent is likely to react with an active site lysine, consistent with previous suggestions. PMID- 8000858 TI - Enzyme-catalysed kinetic resolution of 4-endo-hydroxy-2-oxabicyclo[3.3.0]oct-7-en 3-one and employment of the pure enantiomers for the synthesis of anti-viral and hypocholestemic agents. AB - The endo-hydroxylactone (+/-)-(1) was resolved by enantioselective acetylation using Candida cylindracea lipase or preferentially Pseudomonas fluorescens lipase (pfl). Alternatively the corresponding butyrate (+/-)-(3) was hydrolysed with pfl to give the ester (+)-(1S,4R,5S)-(3) and the alcohol (-)-(1R,4S,5R)-(1). The latter compound was converted into carbovir (-)-(1R,4S)-(12) while the ester (+) (3) was transformed into the delta-lactone (+)-(3R,5S)-(18). The exo hydroxylactone (+/-)-(2) was resolved less efficiently by a trans-esterification process employing pfl and vinyl acetate. PMID- 8000859 TI - Reduction of bicyclo[3.3.1]nonane-2,8-diones with baker's yeast. AB - Reduction of bicyclo[3.3.1]nonane-2,8-dione (1) and its homologues 2 and 3 with baker's yeast affords (1R,5S,8S)-8-hydroxybicyclo[3.3.1]nonan-2-one (4) and its higher homologues 5 and 6 with ca 97% e.e. in 72-86% yields. The absolute configuration of 5 was confirmed by the X-ray crystallographic analysis of its camphanic ester 22. PMID- 8000861 TI - Aminotransferase catalysis applied to the synthesis of a PAF antagonist. AB - (R)-alpha-Methyl-3-pyridinebutanamine (5) was required as a key intermediate for production of the PAF antagonist [(R)-(E,E)-5-(4-methoxyphenyl)-N-1- methyl-4-(3 pyridinyl)butyl-2,4-decadienamide (1). A method meeting the requirements of technical simplicity and economic viability was developed using an aminotransferase ex. B. megaterium to catalyze a kinetic resolution of racemic alpha-methyl-3-pyridinebutanamine (3). 5-(3-Pyridinyl)-2-pentanone (4) produced from the (S)-enantiomer, with co-generation of alanine, is recycled by catalytic reductive amination. PMID- 8000860 TI - Large scale preparation of chiral building blocks for the P3 site of renin inhibitors. AB - Racemic ethyl 2-benzyl-3-(tert-butylsulfonyl)propionate (1) and racemic ethyl 2 benzyl-3-[[1-methyl-1-((morpholin-4-yl)carbonyl)ethyl]sulfonyl] propionate (3) were enantioselectively hydrolyzed by subtilisin Carlsberg generating the respective (S)-acids used as building blocks for renin inhibitors. The esters were readily converted as emulsions at elevated temperature, in a suspended form or a two-phase-liquid system. The enzyme maintained its excellent selectivity and a good activity also at high initial substrate concentrations (up to 50% w/w). The enzymatic reaction and work-up were optimized and scaled up. Emulsion problems during work-up encountered with these highly concentrated mixtures were solved by application of a disk separator for phase separation. PMID- 8000862 TI - L-carnitine via enzyme-catalyzed oxidative kinetic resolution. AB - L-Carnitine of high optical purity was prepared via kinetic resolution using a mutant strain of Acinetobacter calcoaceticus ATCC 39647. This organism preferentially metabolized the D-enantiomer of the racemate to furnish L carnitine. Recovery of L-carnitine was 93%, providing a total weight yield of 46.5% in 92% enantiomeric excess. The mode of degradation of carnitine was shown to proceed via a monooxygenase-catalyzed oxidative cleavage resulting in the formation of trimethylamine and malic acid. The data suggest that the stereoselective metabolism of DL-carnitine is probably the result of differential permeability of the cell membrane towards the optical antipodes. PMID- 8000863 TI - A kinetic study and application of a novel carbonyl reductase isolated from Rhodococcus erythropolis. AB - The newly described carbonyl reductase from Rhodococcus erythropolis (RECR) accepts a broad range of substrates. Based on the kinetic constants of a variety of methyl and ethyl ketones a hypothetical model of the substrate-binding site is proposed. Whether a substrate of interest may be reduced by the RECR can be predicted from this model together with the kinetic data. A study of initial velocities and product inhibition is presented, which shows that the kinetics of the RECR follow a Theorell-Chance mechanism. The pro-R hydride of NADH is transferred by the enzyme to the re face of the carbonyl compounds yielding (S) alcohols. The reduction of methyl 3-oxobutanoate and ethyl 4-chloro-3 oxobutanoate catalyzed by the oxidoreductase lead to the corresponding hydroxy compounds with high enantiomeric purity [enantiomeric excess (e.e.) > or = 99%]. The synthesis of ethyl (2R,3S)-3-hydroxy-2-methylbutanoate was accomplished with high diastereoselectivity (diastereomeric excess = 95%) and enantioselectivity (e.e. > or = 95%). PMID- 8000864 TI - Enzymatic asymmetric synthesis of alpha-methyl arylalkylamines and alpha-methyl arylalkylalcohols by arylalkyl acylamidases. AB - With the novel microbial enzyme, 'arylalkyl acylamidase', optically active alpha methyl arylalkylamines and alpha-methyl arylalkylalcohols have been obtained through enantioselective hydrolysis of their racemic amides and esters. (S) Enantiomers of 1-methylbenzylamine, 1-methyl-3-phenylpropylamine and 1-methyl-3 phenylpropanol of high optical purity (> 94% e.e.) were synthesized with the cells of Nocardia erythropolis IAM 1440 or Cellulomonas fimi AKU 671. (R) Enantiomer of 1-methyl-3-phenylpropylamine and (S)-enantiomer of 1-methyl-2 phenylpropanol of high optical purity (> 95% e.e.) were synthesized with the crude preparation of arylalkyl acylamidase of Pseudomonas putida Sc2 AKU 881. PMID- 8000865 TI - Effect of cyclodextrin on improvement of enantioselectivity in the reduction of ketopantolactone with baker's yeast. AB - Addition of beta-cyclodextrin improves enantioselectivity dramatically in the reduction of ketopantolactone mediated by baker's yeast. It has been found that the selectivity increases with the decrease in concentration of ketopantolactone in bulk solvent, and beta-cyclodextrin controls its effective concentration. The role of beta-cyclodextrin is discussed. PMID- 8000866 TI - Chemical and enzyme-catalysed synthesis of quinoline arene hydrates. AB - Arene hydrates of quinoline have been synthesized by enzyme-catalysed benzylic and allylic hydroxylation of dihydroquinolines in growing cultures of the fungus Mortierella isabellina and in liver microsomal preparations. A preference for allylic hydroxylation was generally observed in eukaryotic systems. Evidence of epoxidation of dihydroarenes by both the fungal and animal enzyme systems was also obtained. The chemical synthesis of these arene hydrates (5-hydroxy-5,6 dihydroquinoline, 6-hydroxy-5,6-dihydroquinoline, 7-hydroxy-7,8 dihydroxyquinoline, and 8-hydroxy-7,8-dihydroquinoline) from the corresponding hydroxy-5,6,7,8-tetrahydroquinolines, has also been accomplished. PMID- 8000867 TI - Microbial hydrolysis of glutaronitrile derivatives with Brevibacterium sp. R 312. AB - The enantiomerically pure (S)-cyano acids 3 and 4 can be obtained by biotransformation with Brevibacterium sp. R 312 of the corresponding prochiral dinitriles 5 and 6, respectively. The hydrolysis is probably a two step process involving a nitrile hydratase and an amidase. In connection with these investigations a facile method for the synthesis of racemic 4-cyano-3 hydroxybutanoic acid derivatives was developed. PMID- 8000869 TI - Effect of conformation of the substrate on enzymatic decarboxylation of alpha arylmalonic acid. AB - The configuration and conformation of a compound are critical factors that determine whether it can be accepted by an enzyme as a substrate or not. We have examined enzyme-catalyzed decarboxylation of some alpha-substituted malonic acids and proposed that the syn-periplanar conformation is required for the substrates to be bound to the active site of the enzyme. Theoretical calculation of potential energy surfaces also supports the conclusion from experimental results. PMID- 8000868 TI - Characterization of a catalytic antibody for stereoselective ester hydrolysis--a catalytic residue and mode of product inhibition. AB - A catalytic antibody which catalyzes stereoselective ester hydrolysis was characterized, and the role of a catalytic Arg residue is discussed in terms of product inhibition. A monoclonal antibody 1C7 generated against the phosphonate 1 was highly stereoselective for (R)-isomer in hydrolyzing racemic ester 2. However, the reaction was almost stoichiometric due to strong inhibition by the product acid 3. One Arg residue in the antibody combining site was essential to the catalysis, and the same Arg was expected to play a dominant role in product inhibition by charge interaction with the negatively charged product acid. Indeed, the antibody experienced much less product inhibition with the hydrolysis of a carbonate ester 7, which yields a neutral alcohol 8 devoid of a negative charge, and exhibited at least 100 turnovers without any loss of activity. In addition, high stereoselectivity for (R)-isomer was still retained. The amino acid sequence and computer modeling of the variable domain of 1C7 suggested that Arg97 in the complementarity-determining region (CDR) of heavy chain was the putative catalytic residue. PMID- 8000870 TI - Acetylesterase from orange peel as biocatalyst for the chemo- and regioselective deprotection of carbohydrates. AB - The enzyme acetylesterase from the flavedo of oranges (EC 3.1.1.6) can advantageously be applied for the chemo- and regioselective deprotection of different types of carbohydrates. It displays a selectivity which in many cases is complementary to the application of other biocatalysts or classical chemical methods. PMID- 8000871 TI - Proteus mirabilis dehydrogenates aldonates and aldarates with an (R)-configured alpha-carbon atom to the corresponding 2-oxocarboxylates. AB - Resting cells of Proteus mirabilis effectively dehydrogenate aldonates and aldarates to the corresponding 2-oxocarboxylates (Figure 2). The prerequisite is an (R)-configured alpha-carbon atom next to the carboxylate group. The oxidation reagent is dimethylsulfoxide and the electron mediator is anthraquinone-2,6 disulfonate (Figure 1). The reactions mostly proceed quantitatively in concentrations up to 0.5 M. The two enzymes necessary for the dehydrogenation, (2R)-hydroxycarboxylate viologen oxidoreductase and dimethylsulfoxide reductase, are present in P. mirabilis in high activities. Nine aldonates have been dehydrogenated to 2-glyculosonates (2-oxoaldonates) and two aldarates to alpha oxo aldarates. As shown with lactobionate and 6-phospho-D-gluconate, derivatives of aldonates can be dehydrogenated too. The apparent Km values of the substrates are often < 1 mM. The products were isolated as sodium or potassium salts with yields between 65 and 98% and characterized. D-xylo-Hex-2-ulosonate obtained from D-gulonate was converted to D-ascorbic acid. PMID- 8000872 TI - Chemoenzymatic access to enantiomeric bicyclo[2.2.1]heptan-2,5-diones. AB - A practical integrated process, combining an enzymatic resolution step with a few chemical transformations, is described for the synthesis of (1R, 4R)- and (2S, 4S)-bicyclo[2.2.1]heptan-2,5-diones 1 of high enantiomeric purity, starting from a standard mixture of (+/-)-endo- and exo-2-acetoxy-5-norbornene. PMID- 8000873 TI - Enhanced stereoselectivity in pig liver esterase catalysed diester hydrolysis. The role of a competitive nucleophile. AB - The enantioselectivity of pig liver esterase catalysed hydrolysis of cis-N-benzyl 2,5-bis(methoxy-carbonyl)pyrrolidine (1) has previously been shown to be very dependent on the reaction conditions. Hydrolysis performed in media buffered with tris(hydroxymethyl)aminomethane (Tris) afforded a monoester with much higher optical purity than hydrolysis in media without Tris. Detailed product studies in a Tris-buffered medium have been performed using NMR-techniques and a 13C labelled ester. The NMR-studies revealed the presence of (2S,5R)-N-benzyl-2 methoxycarbonyl-5-[[[2-hydroxy-1,1- bis(hydroxymethyl)ethyl]amino]carbonyl]pyrrolidine (4) as an intermediate, which together with the isolated product (2S,5R)-N-benzyl-2-carboxy-5-[[[2-hydroxy-1,1 bis(hydroxymethyl) ethyl]amino]carbonyl]pyrrolidine (3) suggested Tris as a competitive nucleophile to water. The increased enantioselectivity seen in the produced (2R,5S)-N-benzyl-2-methoxy-carbonyl-5-carboxypyrrolidine (2) was explained by the preference of Tris to react faster with one of the diastereomeric acyl enzymes over the other. PMID- 8000874 TI - Do carbohydrates play a role in the lignin peroxidase cycle? Redox catalysis in the endergonic region of the driving force. AB - The redox cycle of lignin peroxidase (LiP) is discussed in terms of the Marcus theory of electron transfer. The difference in kinetic behaviour of the two redox couples LiP-Compound I/LiP-Compound II (LiPI/LiPII), respectively LiPII/LiP, in the oxidation of veratryl alcohol is attributed to an estimated increase in reorganization energy of about 0.5 eV for the conversion of LiPII to native enzyme compared to the reduction of LiPI to LiPII. Whereas LiPI/LiPII involves a transition from a low-spin oxyferryl prophyrin radical cation to a low-spin oxyferryl porphyrin system, the conversion of LiPII to native enzyme involves a change in spin-state to high-spin ferric, accompanied by a conformational change of the protein. In addition, a molecule of water is formed after protonation of the oxyferryl porphyrin system by the distal His-47 and Arg-43. Furthermore, the reduction of LiPI to LiPII is observed as an irreversible process. Since the oxidation of veratryl alcohol by oxidized LiP will occur in the endergonic region of the driving force, it is postulated that the thermodynamic unfavourable formation of veratryl alcohol radical cation is facilitated by reaction of a nucleophile with the incipient radical cation. It is further postulated that the ordered carbohydrate residues found near the entrance to the active site channel in the LiP crystal structure play a role in this process. PMID- 8000875 TI - Synthetic polymers as solubilizing vehicles for enzymes in water-poor media. AB - A recent method for exposing enzymes to organic solvents is reviewed. By complex formation between the enzyme and polymers that per se are soluble in organic solvents it is possible to disperse the enzyme in the organic medium in such a way that an optically transparent (in the visible region) solution is obtained. After reaction, the separation of the enzyme from the organic medium can be obtained simply by addition of water. The enzyme can be recovered from the water phase. Physicochemical studies have revealed that the enzyme is more stable in the complex-bound form. PMID- 8000876 TI - Stereoselective epoxidation of 2,2-dimethyl-2H-1-benzopyran-6-carbonitrile. AB - The chiral intermediate (3S,4R)-trans-3,4-dihydro-3,4-dihydroxy-2,2-dimethyl- 2H 1-benzopyran-6-carbonitrile [(+)-trans diol 3] was made by the stereoselective microbial epoxidation of 2,2-dimethyl-2H-1-benzopyran-6-carbonitrile 1. This compound is a potential intermediate for the total synthesis of potassium-channel openers. Several microbial cultures were found which catalyzed the transformation of 1 to the corresponding (3S,4S)-epoxide 2 and (+)-trans diol 3. The two best cultures, Corynebacterium sp. SC 13876 and Mortierella ramanniana SC 13840 gave reaction yields of 32 M% and 67.5 M% and optical purities of 88 and 96%, respectively, for (+)-trans diol 3. A single-stage process (fermentation epoxidation) for the biotransformation of 1 was developed using Corynebacterium sp. SC 13876 and M. ramanniana SC 13840. In a 25-L fermentor, the (+)-trans diol 3 was obtained in 38.6 M% yield with an optical purity of 90% using Corynebacterium SC 13876. The reaction yield of 60.7 M% and optical purity of 92.5% were obtained for (+)-trans diol 3 using M. ramanniana SC 13840. A two stage process for the preparation of (+)-trans diol 3 was also developed using a 3 L cell-suspension (10% w/v, wet cells) of M. ramanniana SC 13840. The reaction was carried out in a 5-L Bioflo fermentor. The concentration of substrate 1 was 2 g L-1 with glucose present at 10 g L-1. After 48 h, (+)-trans diol 3 was obtained in 76 M% yield with an optical purity of 96%.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8000878 TI - Expoxidation of styrene and substituted styrenes by whole cells of Mycobacterium sp. M156. AB - Whole cells of the propene utilizing Mycobacterium sp. M156 (NCIMB 40156) oxidised styrene, 2-,3- and 4-fluorostyrene, 3- and 4-chlorostyrene and 3- and 4 methylstyrenes to their respective epoxides. Rates of oxidation were comparable to that of styrene. alpha-Methylstyrene was also epoxidised at a lower rate, while trans-beta-methylstyrene and 1,2-dihydronaphthalene were poor substrates. In those cases that were investigated, epoxidation occurred with a high degree of stereospecificity. PMID- 8000877 TI - Oxidative coupling of mithramycin and hydroquinone catalyzed by copper oxidases and benzoquinone. Implications for the mechanism of action of aureolic acid antibiotics. AB - The copper oxidases human ceruloplasmin and Polyporous anceps laccase catalyze the oxidative coupling of mithramycin (1) and its aglycone chromomycinone (2) with p-hydroquinone to form new mithramycin-hydroquinone (3) and chromomycinone hydroquinone adducts (4), respectively. Similar adducts could be formed by the nonenzymatic mimic of this reaction using benzoquinone and these aureolic acids in buffer solutions. FABMS of 3 indicated that the hydroquinone moiety was attached to the aureolic acid aglycone. Acid hydrolysis of 3 yielded a compound with the same chromatographic and spectroscopic characteristics as 4. Structure elucidation of 4 by NMR and MS revealed that the hydroquinone was attached to the C-5 position of the aglycone. NMR evidence indicated that 4 consisted of a mixture of ortho-substituted biphenyl rotamers. The mechanism of the copper oxidase catalyzed adduct formation reaction is presumed to involve radical formation through hydrogen removal at the 8-phenolic position, radical isomerization, and coupling with semiquinone radical also formed during enzymatic and nonenzymatic incubations. Identification of the covalent-hydroquinone adduct provides evidence that aureolic acid antibiotics can be metabolically converted to reactive radical intermediates, and it establishes the C-5 position of aureolic acid as an enzymatically reactive site. Unlike mithramycin, the mithramycin-hydroquinone adducts was inactive in the in vivo P388 leukemic antitumor test system. PMID- 8000879 TI - Dissection techniques. PMID- 8000880 TI - Monopolar current, with particular attention to hook dissection in laparoscopic cholecystectomy. AB - Monopolar current has been part of surgical practice for decades. The introduction of laparoscopic surgery has led to new developments in electrosurgery, in instrumentation and in operative techniques. The hook electrode is a device specially created for laparoscopic surgery. Some essentials of modern electrosurgery and the technique of the hook electrode are reviewed, with special emphasis on its use during laparoscopic cholecystectomy. PMID- 8000881 TI - Laser techniques in gynaecology. AB - Lasers have been in use for 15 years in laparoscopic surgery. The CO2-laser in particular has become very popular in the field of gynaecology for the treatment of endometriosis and adhesions. Results achieved with the CO2-laser seem to be superior to those of conventional instruments, although only a small number of randomised prospective studies exist. Fibre lasers, such as the Nd:YAG-, KTP, and Argon-lasers combine vaporisation- and/or coagulation-effects within the same operating instrument. Time-consuming changes of instruments during the procedure are unnecessary. Nevertheless, technical problems and high costs of these laser systems on the one hand, and unfulfilled and unrealistic expectations by physicians and patients alike on the other hand hinder wide-spread use of this technique. PMID- 8000882 TI - Ultrasonic dissection. AB - The tissue-cutting ability of ultrasonic waves takes on practical significance in two instruments: the ultrasonic cavitational aspiratory and the ultrasonically activated scalpel. An understanding of the basic principles involved and the manner in which these instruments function illustrates their advantages in many situations over commonly used electro- and laser surgical techniques. PMID- 8000883 TI - Laparoscopic liver tumour resection with the argon beam. AB - Our initial experience with four minor resections for one malignant and three benign lesions is reported. Dissection was accomplished by mechanical fragmentation and hydrojet. Coagulation was effectively achieved by the argon beam system. Larger vessels were clipped. Three patients were treated laparoscopically and were rapidly discharged after an uneventful postoperative course. The other patient (small hepatocellular carcinoma in cirrhotic liver) had an intraoperative cardiac arrest, probably due to gas embolism. After restoration of normal cardiac activity, the operation was completed after conversion to an open approach. When using the argon coagulator it is necessary to prevent excessive intra-abdominal pressure due to the flow of argon gas and to avoid injury to the hepatic veins, which may cause gas embolism. PMID- 8000884 TI - Laparoscopic liver resection in the Large White pig--a comparison between waterjet dissector and ultrasound dissector. AB - Resection of 16 liver lobes was successfully undertaken laparoscopically in anaesthetised Large White pigs. These animals proved to be suitable for the instruments used in human laparoscopic procedures. It was planned to undertake a comparison between the waterjet and ultrasound dissectors, but this proved impossible because of the development of a thick intraabdominal mist during dissection with the waterjet dissector. The ultrasound dissector was effective in dissecting the intraparenchymal hepatic structures, especially the portal vein and the hepatic vein. These blood vessels were safely secured with endoclips, while bleeding points on the resection surface were coagulated with an argon beam coagulator. The liver specimens removed were approximately 75 g in weight. All ultrasound-dissected animals survived for 10 days. Post-mortem evaluation showed two cases of wound infection, one case of subphrenic abscess and two cases of biloma. Our results emphasise the potential of laparoscopic resection techniques for formal or at least peripheral liver resections in humans. PMID- 8000885 TI - Histologic effects of different technologies for dissection in endoscopic surgery: Nd:YAG laser, high frequency and water-jet. AB - Precise cutting combined with reliable coagulation of the margins of the lesion is an important requirement for dissection techniques in endoscopic surgery. These requirements are met by the two most common ancillary energy sources applied for endoscopic dissection today, electrosurgery and "thermal lasers", mostly the Nd:YAG. For the comparison of the histological effects of monopolar and bipolar high frequency with the Nd:YAG laser an experimental in vitro and in vivo study has been performed. In order to evaluate the advantages of non thermal dissection for endoscopic procedures, a water jet cutting system was included in the in vitro study. In parenchymatous tissue the water jet was found to be the least traumatic technique, followed by bipolar high frequency, laser and monopolar high frequency. The water jet was not applicable for intestinal dissection since uncontrolled bloating of the rectal wall with uncontrolled disruption of the tissue layers occurred. A general disadvantage is that secure haemostasis in the line of incision is hard to achieve. In the microscopic comparison of the shape of the incision, the Nd:YAG laser produced the smoothest lesions with well-defined margins. The monopolar technique was more often associated with irregular and sometimes fissured margins. These results were confirmed in the in vivo part of the study (Transanal Endoscopic Microsurgery). PMID- 8000886 TI - Experimental evaluation of water-jet dissection in endoscopic surgery. AB - The problems associated with high-velocity high-pressure water-jet dissection were investigated by in-vivo experiments using endoscopic equipment. Three problems were identified: backspray with fouling of the optic, poor control of the depth of cut, and detachment of tissue fragments and isolated cells which contaminate the operative field. The first two problems have been resolved by adoption of a hooded hand-piece and the incorporation of an adjustable back stop. A "dry" system which enables the evacuation of the back spray may deal with the problem of contamination of the operative field by detached cells but further in vivo experiments are needed to confirm this. Until then, water-jet cutting is considered unsafe for both open and endoscopic surgery in patients undergoing extirpative procedures for cancer because of the risk of tumour seeding within the peritoneal cavity. PMID- 8000887 TI - Medicotechnical basics of surgery using invasive ultrasonic energy. AB - Surgical techniques that use invasive ultrasonic energy for dissection and aspiration are a most advantageous extension of the methodological spectrum of conventional and endoscopic surgery. This article presents the technico-physical basics of the technology of ultrasonic surgery and the specific mechanisms underlying its effects on biologic tissue. A synopsis is given of the main fields of application of the ultrasonic aspirator in various surgical disciplines. PMID- 8000888 TI - Ultrasonic dissection in combination with high-frequency surgery. AB - Ultrasonic surgery is a technique used for tissue-selective dissection. High frequency surgery, on the other hand, is a technique which permits largely non selective cutting of all tissue except bone. Whereas ultrasonic surgery has no haemostatic effect, high-frequency surgery is highly effective for haemostasis. The combined use of ultrasonic surgery and high-frequency surgery, particularly in endoscopic operations, can unite the advantages of both methods and thus improve surgical techniques or even permit applications which are difficult or impracticable with ultrasonic surgery or high-frequency surgery alone. Various possibilities for combining ultrasonic surgery and high-frequency surgery have not been exploited to date and therefore remain open for future development. PMID- 8000889 TI - Thermal and non-thermal laser dissection. AB - Conventional cw-(continuous wave) laser systems such as the CO2- and Nd:YAG-laser are well established in medical therapy for tumour resection, tissue cutting, vaporisation and coagulation. The argon-ion laser is also a "classic" laser type with applications in ophthalmology, dermatology and for micro-surgery. New lasers in the IR-range of the optical spectrum appear on the market as pulsed lasers for tissue ablation searching for their specific fields of application. There is some confusion about laser applications at the moment until the new techniques and methods have proven to be really superior to other techniques. But knowing more about the laser tissue interactions one can estimate the potential of a new laser source. This article gives a short overview over the actual laser systems and the reaction processes with soft and hard tissue. PMID- 8000890 TI - The Kieturakis balloon dissector--an aid to the extraperitoneal approach for laparoscopic repair of groin hernias? AB - A novel balloon device was evaluated as an access and dissection aid for laparoscopic hernia surgery based on the Dulucq method. The device was found to provide reliable access and good preliminary dissection with a saving in operating time. It is of particular value when learning laparoscopic hernia surgery. PMID- 8000891 TI - Technique for CT guided microendoscopic dissection of the spine. AB - The indications for percutaneous nucleotomy techniques are limited to disk herniation without dislocated free fragments. In cases with free fragments we have developed a new technique for percutaneous sequestrectomy. Under CT and fluoroscopic guidance spinal endoscopy was performed. In the past, percutaneous diskectomies were X-ray-guided with or without endoscopy. In this paper we describe the combination of CT-scanning, fluoroscopy and microendoscopy for guidance of nucleotomes, lasers, microendoscopes and micro-instruments. The technique was performed on 20 patients (17 outpatients) with chronic back pain. To date no major complications occurred. The method offers an effective outpatient treatment of small free fragments and scar tissue in the spinal canal and the foramen. PMID- 8000892 TI - Dissection technologies. PMID- 8000893 TI - Designing media fill tests. PMID- 8000894 TI - Good validation practices: FDA issues. PMID- 8000895 TI - Stability of rhbFGF as determined by UV spectroscopic measurements of turbidity. AB - Loss of potency of a protein formulation due to precipitation of the protein is a major concern to the pharmaceutical scientist. A simple screening method was developed to study the effect of excipients on protein precipitation. It will not provide accurate stability data but it allows the rejection of excipients that may interfere with the stability of a protein formulation. The method is based on measuring the increase in turbidity at 277 nm by UV-spectroscopy and was sensitive and reproducible enough to obtain data within 15 hr at 30 degrees C or 40 degrees C, which will allow prediction of precipitation behavior that would need with conventional methods 2-3 years. Human recombinant basic fibroblast growth factor (rhbFGF or bFGF) was formulated at various pH-values as well as in the presence of various concentrations of preservatives, surfactants, gelling agent, EDTA, NaCl, sodium sulfate, sucrose, and glycosaminoglycans (GAG). Most excipients increased bFGF aggregation rate when their concentrations were increased. Exceptions were heparin and some of its derivatives, and sodium sulfate; high concentrations of sucrose and sodium chloride suppressed aggregation. PMID- 8000896 TI - Protection of lactate dehydrogenase against protease digestion by encapsulation in liposomes. AB - Lactate dehydrogenase (LDH) was entrapped in phosphatidylcholine liposomes to evaluate the protective effect of liposomes against protease digestion. Three different preparations of LDH either encapsulated in liposomes, unencapsulated in liposomes or in the absence of liposomes were incubated with the protease trypsin. The loss of LDH activity was measured at intervals over a 12-hour period. The degradation rate of LDH was found to be the same when LDH was unencapsulated in the presence or absence of liposomes. However, when LDH was entrapped in liposomes the degradation rate was 4 to 24 folds slower. This finding indicates that encapsulation of a protein in a liposome protects the protein from the degrading effects of a protease enzyme. PMID- 8000897 TI - Role of quality control in validation of biopharmaceutical processes: case example of clean-in-place (CIP) procedure for a bioreactor. AB - If ever clear instruction and close teamwork is needed, it is in the validation of manufacturing processes. All members of the Validation Team need to understand how the Quality Control testing fits into the overall validation work plan. This affords the team members the opportunity to understand how data will be used and avoids a situation where the test results either invalidate or inadequately support the validation plan. A case example is presented for an approach used to validate Clean-in-Place (CIP) procedures for 1600 L bioreactors which are operated on a campaign basis for multi-biopharmaceutical synthesis. PMID- 8000898 TI - Effect of cryoprotectants on freezing, lyophilization, and storage of lyophilized recombinant alpha 1-antitrypsin formulations. AB - Stabilizing effect of several commonly used cryoprotectants, namely lactose, sucrose, and polyvinyl-pyrrolidone (PVP), on recombinant alpha 1-antitrypsin (rAAT) were studied. A solution of rAAT in a phosphate/citrate buffer (pH 7.0) was made with and without a given cryoprotectant and filled into small vials. The vials were frozen on shelf, at -40 degrees C in a lyophilizer. At the end of the freezing cycle, half of the batch was thawed at ambient temperature and the other half was continued to the completion of lyophilization. Sample vials taken before freezing, after thawing, and after lyophilization were analyzed for total rAAT protein, monomeric content, and elastase-inhibitory activity. Results indicated that neither freeze-and-thaw nor lyophilization caused any damage to rAAT, contrary to what was generally believed. The control formulation (i.e., without a cryoprotectant) performed as good as those containing cryoprotectants. Freezing rates and protein concentration in formulation did not influence the stability of rAAT either. Lyophilized rAAT samples retained the activity and purity during the 12 month stability period, at room temperature and 2-8 degrees C. PMID- 8000899 TI - Drug delivery systems for the future. AB - Parenteral drug delivery systems have the potential to make drugs both safer and more effective. While research in this field has been active for over 30 years, the current fiscal constraints of health care delivery add a greater degree of urgency to finding a working system. The three competing technologies currently under development include prodrug or zymogen-like systems, simple soluble macromolecular systems, and complex particulate multicomponent systems. In this review, the advantages, disadvantages, and areas for further development of these three basic technology systems are compared and contrasted; the biophysical constraints are considered; and a model solution system using surface modified nanocrystalline ceramics is described. PMID- 8000900 TI - A new coincidence model for single particle counters, Part II: Advances and applications. AB - Accuracy, acceptance limits and methods for U.S.P. (788) contaminating particle assays published in the XXII Revision are refined in U.S.P. XXIII. In both Revisions, although different numerical values and methods are employed, particle contamination limits remain constants for all S.V.I. container volumes. The effect of this quality standard is high particle concentration acceptance limits in the smallest S.V.I. container sizes. The effect of these high concentrations is to introduce both undercount errors and false counts into U.S.P. (788) SVI contaminating particle assays. There is general agreement that the count of high concentrations of particles by a single particle light extinction counter result in an increase of the average size of the distribution of particles reported and a decrease in their total number. The error mechanism is termed "signal coincidence." Understanding and control of both these problems is unified with the introduction of the count efficiency parameter. Part I of this paper makes available two core concepts with which evaluation and control of coincidence error in single particle counters can be accurately quantified. These two core concepts are the "Particle Triggered Poisson Model," a new more accurate statistical model of the particle counting process and a concentration measure that includes the effect of particle size on the counting capability of a detector. Use of these concepts make it possible to evaluate particle detector count efficiency capability from experimental data of the coincidence effect. This is an application paper. It combines the theory in the Part I paper with the replicability of particle counters into a simple test protocol. The test results can be used to calculate a contour of particle size and count within which both undercount errors and the introduction of false counts into U.S.P. (788) particle assays are controlled. From the data analyzed it can be seen that any single particle size test cannot effectively evaluate detector performance. The use of the theory and methodology described can help realize the intent of the U.S.P. (788) SVI particle contamination assay. PMID- 8000901 TI - The worst combinations of child abuse and neglect. AB - We have studied the impact of various kinds of abuse and neglect on the child's perception of himself and his future. We found, when considering physical abuse, physical neglect, verbal abuse, emotional neglect, and sexual abuse, that less than 5% of these mistreatments occurred in isolation. Since the vast majority of mistreated children are subject to more than one kind of abuse or neglect, it was important to delineate which combinations have the greatest effect. We found that a combination of physical neglect, physical abuse, and verbal abuse had the greatest impact on children, affecting such things as their enjoyment of living and hopes for the future. An early age of onset for verbal abuse and emotional neglect was significantly associated with greater severity and frequency of mistreatment. Neglect appears to be a precursor to abuse in many cases. PMID- 8000902 TI - Development and survival: a study of children at risk living in adverse psychosocial milieu. AB - The aim of this study is to describe the situation of children at risk in psychosocially disadvantageous milieus, how these children cope with their situation, and which survival strategies they do develop. A summary of longitudinal research in child development and epidemiology shows that the reasons for psychopathology are complex and multidimensional. What is not known is the very process in which the child forms his or her experiences and resources into a constructive or less constructive strategy for handling the forces that build up a stressful milieu. To penetrate and learn something from such a process a longitudinal study concerning 12 preschool children during a 4-year period, was designed. Methods used were Griffith's psychomotorical test, a behavior inquiry, case sheet notes, and interviews with children, their families and the staff involved. The result showed three girls developing mainly constructive (moderating) strategies, the other children demonstrated more or less destructive, outerdirected, or innerdirected patterns. All boys in the study demonstrate less constructive strategies. PMID- 8000903 TI - Opinions on the traumatizing effects of child sexual abuse: evidence for consensus. AB - The aim of the study was to investigate peoples' views of characteristics associated with child sexual abuse (CSA) and place them in order of severity for subsequent trauma. Clinically relevant characteristics of CSA were presented in the form of a questionnaire to a sample of professionals working with CSA, a sample of student nonprofessionals and a sample of patients with eating disorders including a high proportion of CSA victims. A significant consensus existed across the three samples in the ranked order of characteristics from most to least severe for perceived adverse long-term outcome. Respondent sex, social class, or past sexual abuse experience had no significant effect on this concordance. The findings of this study have shown that professional, nonprofessional, and psychiatric patients opinions on CSA severity are consistent and coincide with clinical observations and empirical evidence. It is argued that a shared consensus on traumatic effects of CSA characteristics is important for the therapeutic process and may prove useful as a guideline for the assessment of severity in CSA cases. PMID- 8000904 TI - How children perceive the medical evaluation for suspected sexual abuse. AB - This study investigated how 99 children who were examined for suspected sexual abuse (SSA) perceived their own medical evaluation experiences. Each child was interviewed about the degree of pain and fear associated with the experience, the kindness of the doctor, general fear of doctor visits, and degree of fear associated with a hypothetical second examination. The majority of children did not perceive their SSA examination to be strongly negative. However children did report greater fear associated with the SSA evaluation compared to an ordinary doctor visit. Using multiple regression, general fear of doctor visits and fear and pain associated with the SSA examination contributed to the prediction of intensity of fear about a hypothetical second SSA evaluation. Perceived kindness of the doctor, patient sex and age, and physician sex and age did not contribute to the regression equation. The relatively low reported rate of intense distress associated with medical evaluation of SSA suggests that fear and pain can be minimized and effectively managed for many children. The results of the regression analysis suggest that previous negative medical experiences may play an important role in determining how a child interprets the experience of an SSA medical evaluation. PMID- 8000905 TI - Emotional, behavioral, and HIV risks associated with sexual abuse among adult homosexual and bisexual men. AB - From May 1989 through April 1990, 1,001 adult homosexual and bisexual men attending urban sexually transmitted disease clinics were interviewed regarding abusive sexual contacts during childhood and adolescence. Sexual abuse was found to be significantly associated with mental health counseling and hospitalization, psychoactive substance use, depression, suicidal thought or actions, social support, sexual identity development, HIV risk behavior including unprotected and intercourse and injecting drug use, and risk of sexually transmitted diseases including HIV infection. Data suggest that sexual abuse may have a wide-ranging influence on the quality of life and health risk behavior of homosexual men. Increased awareness as to the potential outcomes of male sexual abuse is critically important to the design and implementation of medical and psychological services for sexually abused men. PMID- 8000906 TI - Masculinity and femininity in male and female perpetrators of child sexual abuse. PMID- 8000907 TI - The syndrome of Munchausen by proxy. PMID- 8000909 TI - Serum prolactin-binding protein (PRL-BP) of human and rat are identified as IgG. AB - Heterogeneity of circulating prolactin in various species including rat and man is well known. We have recently shown that PRL was able to bind to a protein of high molecular weight in plasma obtained from estradiol treated ovariectomized females rats. This study was undertaken to look for a possible PRL-binding in woman serum and to identify the PRL-BP in both rat and human sera. Pooled sera from normal women taking oral contraception and from women on the 3rd trimester of pregnancy were purified on affinity chromatography column, prepared with sepharose 4B-CNBr coupled to oPRL (ovine PRL). Elution resulted in a protein of 160 kD mol wt when subjected to SDS PAGE in non reducing conditions. Under reducing conditions 2 forms of 50 and 27 kD were found. The 160 kD and the 50 kD forms were able to bind to hPRL. The 3 forms (160, 50 and 27 kD) were recognized by monoclonal antibodies against PRL receptors. Both the 50 and 27 kD forms obtained from rat and human sera were sequenced and revealed to be the heavy and light chain of IgG1. This result was confirmed by specific immunoprecipitation of the PRL-BP by antibodies against human and rat IgG. This study showed, that autoantibodies to PRL were present in rat and human sera, even in physiological conditions such as pregnancy. PMID- 8000908 TI - Munchausen syndrome by proxy: a study of psychopathology. AB - Munchausen Syndrome by Proxy (the fabrication of illness by a mother in her child) is often a serious form of child abuse that has been recognized increasingly over recent years. Approximately one-half of the mothers in this study had either smothered or poisoned their child as part of their fabrications. Lifetime psychiatric histories are reported for 47 of the mothers. Thirty-four had a history of a Factitious or Somatoform disorder, 26 a history of self harm, and 10 of alcohol or drug misuse. Nine mothers had a forensic history independent of convictions related to child abuse. Nineteen of these mothers were interviewed from 1-15 years after the original fabrications. The most notable psychopathology was the presence of a personality disorder in 17 of the mothers, which were predominantly Histrionic and Borderline types. Most subjects, however, met the criteria for more than one category of personality disorder. PMID- 8000910 TI - [Change of cholesterol oxidase of Brevibacterium sterolicum and substrate specificity]. AB - Cholesterol oxidase modified by hydrogen peroxide is inactive with cholesterol solubilized in buffer with surfactants. Pregn-5-en-3 beta-ol when solubilized in the same conditions and substrates soluble in buffer, like 3 beta-hydroxy-androst 5-en-17-one or 3 beta-hydroxy-androst-5-en-17 beta-carboxylic acid are substrates of the modified enzyme. The observed loss of activity on cholesterol could be due to the inability of the oxidized cholesterol oxidase to extract cholesterol from mixed cholesterol/surfactant aggregates. Cholesterol oxidase on storage undergoes modifications close to those with hydrogen peroxide and care should be taken for the use of cholesterol oxidase as cholesterol probe. PMID- 8000911 TI - Complete sequence of rat MAP2d, a novel MAP2 isoform. AB - MAP2 proteins are among the major microtubule-associated proteins in the vertebrate nervous system. The high molecular weight proteins MAP2a, MAP2b and the low molecular weight protein MAP2c are encoded by distinct mRNAs generated by alternative splicing from the same primary transcript. MAP2c is primarily found in embryonic and neonatal brain. Using primers selected in the 5' and 3' non coding regions of the rat MAP2c sequence and reverse transcription-coupled PCR from adult rat brain RNA, we have amplified and sequenced the entire coding region of a novel MAP2 isoform containing a 93 base pair insertion. Sequence analysis reveals that the additional exon encodes a domain that is highly homologous to repeats found in the 3' end of the coding region of MAP2, MAP4 and Tau mRNA sequences. In these microtubule-associated proteins, the domains encoded by the repeats are involved in microtubule binding and bundling. PMID- 8000912 TI - Rat long-term bone marrow culture as a model for transient production of multinucleated giant cells into suspension culture fraction and for steady mineralization process of adherent stromal cells. AB - Under in vitro conditions rat bone marrow stromal cells induced into osteogenic differentiation by beta-glycerophosphate, exogenous ascorbic acid and dexamethasone are able to produce a mineralized matrix. Here we describe adult rat long-term bone marrow cultures (LTBMC), deprived of these substances. Mineralization process in stromal adherent cells occurred after 1 month of incubation and was proved by means of X-ray electron microprobe. The high content of sulfur in the extracellular matrix surrounding the mineralized nodules suggests non-distrophic pathway of Ca/P deposition. During the first 2 weeks of incubation the extensive production of multinucleated tartrate-resistant acid phosphatase (TRAP) positive and TRAP negative giant cells occurred into the suspension fraction of the cultures. Rat LTBMC may serve as a model for the investigation of differentiation of osteoblastic progenitors and their interactions with multinucleated TRAP positive cells. PMID- 8000913 TI - Myogenic cells in the rat embryonic brain stem. AB - The principal finding of this study is the establishment of culture conditions that permit the survival of a very limited population of muscle precursor cells from the embryonic and neonatal rat brain stem, with these cells displaying the capacity to differentiate into contractile striated fibers under these in vitro conditions. Examination of desmin and troponin T expression by immunoperoxidase analysis revealed the presence of the two muscle proteins in the mononucleated precursors and in differentiated multinucleated myotubes. In vivo, examination of sections at corresponding stages revealed the simultaneous presence of troponin T, desmin, and lectin binding sites--a property of endothelial cells--association which appears to be transitory, since it is no longer detectable in the adult brain. The presence of the choroid plexus neuroepithelium, in close vicinity with TnT+, desmin+cells located in a limited zone of the brain stem, as well as the stage of expression for these markers suggest an interaction between brain myogenic cells and the onset of the embryonic circulation. The question of the embryological origin of the brain myogenic cells is discussed. PMID- 8000914 TI - Congenital muscular dystrophy with merosin deficiency. AB - Congenital muscular dystrophy is one of the most frequent and severe childhood muscular dystrophies. Several forms of this disease have been described. The form associated with marked central nervous system disturbances, frequent in Japan, is known as Fukuyama congenital muscular dystrophy and was recently linked to chromosome 9. The most frequent form observed in occidental countries appears to be clinically characterized by exclusive involvement of skeletal muscle, and has been identified by clinico-pathological features which are often fallacious. A predominant histopathological feature is the marked increase in endomysial collagen tissue. We investigate whether laminin, a major component of the extracellular matrix, which is linked to the subsarcolemmal cytoskeleton by a large oligomeric complex of dystrophin-associated glycoproteins, could be involved in this form. We observed a specific absence of merosin, the laminin M chain, in 13 patients affected by classical non-Japanese form of congenital muscular dystrophy. This result allows the precise identification of a particular form of congenital muscular dystrophy and gives a clue to understanding its molecular pathogenesis. PMID- 8000915 TI - [Mutations of RET proto-oncogene in Hirschsprung disease]. AB - Hirschsprung's disease (HSCR) is a common condition (1 in 5,000 live births) resulting in intestinal obstruction in neonates and megacolon in infants and adults. This disease has been ascribed to the absence of autonomic ganglion cells, which are derived from the neural crest, in the terminal hindgut. Segregation analyses have suggested incompletely penetrant dominant inheritance in familial HSCR. Recently, a gene for HSCR has been mapped to chromosome 10q11.2. No recombination was observed between the disease locus and the locus for the RET proto-oncogene, a protein tyrosine kinase gene expressed in the cells derived from the neural crest. Here we report on nonsense and missense mutations in the extracellular domain of the RET protein (exons 2, 3, 5 and 6) in 6 unrelated probands and show that the mutant genotypes segregate with the disease in HSCR families. Mutations of RET have been previously reported in multiple endocrine neoplasia type 2A (MEN 2A). Thus, germ-line mutations of the RET gene may contribute either to developmental anomalies in HSCR or to inherited predisposition to cancer in MEN 2A. PMID- 8000916 TI - Interaction of von Willebrand factor with platelets activated by thrombin or a synthetic 7-amino acid peptide derived from the cleaved thrombin receptor. AB - Thrombin and the 7-mer agonist peptide from its receptor (SFLLRNP) were compared for their ability to promote the binding of vWF to platelets. Identical Ca(2+) dependence and kinetics of activation were observed. Studies of inhibition of the binding by a series of monoclonal antibodies to GPIb, GPIIb/IIIa and vWF and experiments performed using platelets from patients with Glanzmann thrombasthenia or Bernard-Soulier syndrome enabled to identify GPIIb/IIIa as the receptor of vWF. Binding isotherms of vWF in the presence of an excess of either agonist yielded a similar number of binding sites but an apparent dissociation constant slightly but consistently higher with the 7-mer peptide than with thrombin. The latter point was confirmed by studying the binding of limiting amounts of vWF to platelets as a function of the agonist concentration. The lower affinity in the presence of 7-mer peptide was not corrected by adding increasing amounts of FPR thrombin, a derivative with irreversibly blocked active site but retaining the binding properties of the active enzyme. Conversely, the higher affinity observed with thrombin was decreased when platelets were treated with Serratia protease which selectively cleaved GPIb but did not affect the function of the thrombin receptor and GPIIb/IIa. Our data thus suggest that both the 7-mer peptide and thrombin are able to induce the assembly of functional GPIIb/IIIa.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8000917 TI - Collective adaptation in a statistical model of an evolving population. AB - We simulate asexually and sexually reproducing model populations evolving in a rugged fitness landscape where fit and unfit genotypes are distributed at random, and where all fit genotypes have the same a priori probability of reproduction. Varying the fraction chi of unfit genotypes at a fixed mutation rate we observe a strikingly different behavior for the two reproduction mechanisms. For the asexually reproducing population, the effective mutation rate lambda decreases roughly proportionally to (1-chi), and the fraction delta of sterile individuals- processing an unfit genotype--accordingly increases roughly proportionally to chi. On the other hand, lambda remains approximately constant (and delta increases proportionally to chi) for small values of chi:but, at a critical value chi*, both lambda and delta suddenly drop. This corresponds to the transition to an adaptive regime where the average fitness of the population is enhanced. We show how this transition can be interpreted in terms of an improvement of the collective fitness of the population. PMID- 8000918 TI - Life and near-death in the intensive care unit. A personal experience. AB - Being seriously ill, even once, is an experience from which one learns a great deal. To feel the loss of control, the pain, and the worry about unfulfilled responsibilities at home and at work forever provides one with the motivation to deal with these issues when confronted with sick people. To understand that each illness has unique effects on a patient and that these patients almost always trust us, gives us the confidence to use our training and experience to do what we know is right for them. We should be confident that if these lessons are internalized and applied, patients and their caretakers will benefit. PMID- 8000919 TI - Improving patient tolerance of mechanical ventilation. Challenges ahead. AB - The development of psychopharmacology and anesthesia practice in the ICU has lagged well behind the development of similar practices in other settings, notably the operating room. Because of important differences in the severity of organ dysfunction and the duration of treatment, however, lessons learned in other settings cannot be applied directly to the ICU. A fresh conceptual framework is needed to identify indications for sedating drugs and muscle relaxants in the ICU. New assessment tools are needed, both for clinical research and for clinical practice. More information is needed on the pharmacokinetics, adverse effects, and comparative costs of psychoactive drug use in the ICU. Practice guidelines are needed to improve efficacy and reduce errors associated with these drugs. The challenge is considerable. The reward is a more humane ICU experience for critically ill patients. PMID- 8000920 TI - Anxiety and delirium in the intensive care unit. AB - To be in respiratory distress is to be anxious. To be mechanically ventilated is to be grossly uncomfortable at best. To undergo weaning in the presence of possible severe respiratory compromise, again, inevitably is anxiety provoking. Assessment of the contributing causes of agitation is essential if patients are to be managed properly. Personality factors may make different contributions to agitation, and necessitate different management approaches. One patient seeks control and another regresses to dependency more easily. Delirium, a common base for agitation, cannot be reassured away or resolved by anxiolytic agents; its root causes need to be corrected before a favorable outcome will ensue. Effective management takes a sophisticated, multidisciplined team, skilled in the physiologic and psychological management of patients. The purpose of a respiratory intensive care unit is to restore respiratory effort and integrity. The anxious patient has difficulty cooperating with weaning and respiratory toilet. The delirious patient cannot cooperate with anything. Until these agitated behaviors are differentiated and resolved, the patient remains at respiratory risk. PMID- 8000921 TI - Disturbances of sleep in the intensive care unit. AB - Sleep can be extremely difficult to achieve in ICUs. Sleep deprivation is a major problem in the ICU and physicians should be aware of the effects of sleep deprivation on physiologic and immune function. Sleep deprivation has been associated with the ICU syndrome. Multiple factors interfere with sleep in the ICU; the single most significant cause of sleep disruption in the ICU is noise. Effective means of controlling noise and sensory overload in ICU patients must be developed. Nonpharmacologic options to enhance sleep should be considered in all ICUs. Sleep should never be considered a luxury in the ICU; it is an essential physiologic need. PMID- 8000922 TI - Nonpharmacologic management of patient distress during mechanical ventilation. AB - Patients on mechanical ventilators experience distress related to the endotracheal tube, the critical care environment, and the critical illness. The strategies suggested here to limit distress--therapeutic relationship building and communication, cognitive-behavioral therapies, and contracted family visiting -all can be implemented by critical care providers. A growing research base documents the success of these interventions in intubated patients. PMID- 8000923 TI - Pharmacology of intravenous sedatives and opioids in critically ill patients. AB - Many agents are available for sedation of agitated, delirious patients. In general, they should be administered intravenously to achieve a painless, more rapid, and more reliable onset of action. Proper selection of an agent requires understanding the basic principles discussed in this article, including the T-1/2 alpha and T-1/2 beta and the side-effect profile associated with each class of drugs, as well as for each agent. As a group, BNZs tend to be the safest and most predictable, and can be titrated easily when administered intravenously. Neuroleptic agents such as haloperidol may act synergistically with BNZs, resulting in control of agitation without significantly depressing the patient's level of consciousness or respiratory drive. Barbiturates, highly effective sedatives, more profoundly depress the respiratory and cardiovascular systems, and probably should be reserved for the severely agitated patient who cannot be controlled otherwise. Etomidate and propofol, useful for short-term procedures, probably should be avoided for long-term use in the agitated patient because of potentially serious side effects. Opioids should be used to provide adequate pain relief and to supplement other sedatives. Inadequate doses or dosing regimens should be avoided. Once sedation has been achieved, control usually can be maintained with continuous intravenous infusions of BNZs, perhaps in combination with a continuous infusion of an opioid or intermittent administration of a neuroleptic agent. With goal-oriented titration of the pharmacologic therapy, patients can be maintained safely in a sedate, calm state; intermittent periods of agitation, alternating with periods of severely depressed level of consciousness, can be avoided. Finally, when pharmacologic suppression of agitation and delirium is needed, the patient must be evaluated fully to determine the underlying cause of the confusional state. PMID- 8000925 TI - Management of pain in mechanically ventilated patients. AB - Acute pain management in critically ill ICU patients is an area that needs increased attention. Modern techniques exist that can help speed recovery and reduce duration of ICU and, potentially, hospital stay. Application of contemporary knowledge in this area benefits both clinician and patient. PMID- 8000924 TI - Pharmacologic treatment of brain failure and delirium. AB - The critical care unit is a place where multiple organ system failure can be effectively reversed by highly technologic treatment innovations. That same technology can confer a great deal of stress on the patient, leading to the unique syndrome of integrative brain failure. Exacerbating factors, such as pain, anxiety, and discomfort, can ultimately result in severe agitation syndromes. This article outlines uniquely specialized treatments for these syndromes and the outlook for future therapies. PMID- 8000926 TI - Pharmacology of neuromuscular blocking agents in the intensive care unit. AB - In critically ill patients, organ function, blood flow, and caregiving personnel change constantly. The risks inherent in paralyzing a patient, such as those of positioning (nerve injuries, stasis injuries) and ventilator disconnection are compounded by the duration of paralysis in the ICU. When used with attention to the pharmacologic properties, patient organ function, and cost, however, muscle relaxants are a useful adjunct to ICU management. PMID- 8000927 TI - Prolonged muscle weakness after neuromuscular blockade in the intensive care unit. AB - As noted, quadriparesis with reduced reflexes and difficulty with ventilator weaning may be seen as a result of a number of neuromuscular disorders. The clinical approach relies on exclusion of a central cause first, followed by careful examination of peripheral nerve and muscle function. Persistent neuromuscular blockade should be excluded initially because it is a readily reversible condition. Use of a train of four stimulation with a peripheral twitch monitor can quickly establish integrity of conduction across the neuromuscular junction. If necessary, further electrophysiologic studies allow differentiation among the relevant diagnostic possibilities. CIP is characterized by nerve conduction and EMG findings consistent with axonal degeneration of sensory and motor fibers. GBS is distinguished by evidence of demyelination on nerve conduction studies, in addition to elevated spinal fluid protein. Persistent neuromuscular blockade is identified by a decremental response on repetitive stimulation studies of neuromuscular transmission. The acute myopathy following neuromuscular blockage does not involve sensory responses. Needle EMG examination reflects a myopathic pattern, rather than a neurogenic one as seen in CIP or GBS. In myopathic patients who are unable to move their limbs at all (precluding a full EMG examination), a muscle biopsy identifies muscle as the site of involvement. PMID- 8000928 TI - Monitoring and preventive care of the paralyzed patient in respiratory failure. AB - It is our belief, based on our experience with the Dulin-Williams protocol, that the safe use of a continuous-infusion NMBA is optimized when a constant current peripheral nerve stimulator is used to monitor the depth of neuromuscular blockade. This protocol should facilitate the chance of adverse effects, thereby increasing the quality of patient care and outcomes within the critical care setting. PMID- 8000929 TI - Neuromuscular blocking agents in the management of respiratory failure. Indications and treatment guidelines. AB - Local custom continues to dictate the clinical use of NMBDs in critically ill patients with respiratory failure. The safety of long-term administration of NMBDs to critically ill patients remains of great concern. Studies that clearly delineate the cause of severe myopathies and neuropathies in critically ill paralyzed patients remain to be performed. Because it appears these disorders may be related to the administration of drugs with steroidal structure, we believe it is prudent to avoid such drugs, if possible, in critically ill patients. We therefore continue to use curare, a nonsteroidal drug with a long history of safety, for long-term paralysis in these patients. Similarly, we believe that it is prudent to monitor the efficacy of NMBDs via the routine use of ulnar nerve stimulation. Patient movement in the face of adequate neuromuscular blockade as assessed by ulnar nerve stimulation then can be treated by deepening the level of sedation rather than by continually increasing the dose of the NMBD. PMID- 8000930 TI - Overview of improving tolerance of long-term mechanical ventilation. AB - In summary, advances in critical care and mechanical ventilation have resulted in an increased salvage of critically ill patients, a number of whom require long term ventilation as a means of life support. In addition, the total number of patients receiving long-term ventilation has increased dramatically over the past couple of years, and they now are treated in many different locations throughout the health care delivery system (the intensive care unit, general medical floor, specialized weaning units, and the home). Moreover, patients who require long term ventilation usually suffer from a complex blend of medical, physiologic, and psychological disorders that may impair tolerance of chronic ventilation. Careful evaluation and systematic treatment of psychological, medical, and physiologic disorders, coupled with optimized ventilator settings, may improve patients' tolerance and maximize their functional capacity. PMID- 8000931 TI - Nutritional management of the metabolically stressed patient. AB - The nutritional management of the critically ill metabolically stressed patient has changed drastically within the last two decades. Alterations in carbohydrate, fat, and protein metabolism following severe injury affect effective substrate utilization and the provision of nutritional or metabolic support. This article describes the acute alterations in carbohydrate, fat, and protein metabolism during severe metabolic stress; reviews nutritional assessment and requirements during metabolic stress; and presents recent findings that influence nutritional support during metabolic stress. The role of gut in the provision of nutritional support and the pharmacologic properties of select enteral nutrients are reviewed. PMID- 8000933 TI - Pathophysiology of pulmonary edema. AB - Pulmonary edema is a frequent and common cause of death in patients in critical care settings. It is seen as a complication of myocardial infarcts, hypertension, pneumonia, smoke inhalation, and high-altitude pulmonary edema. Pulmonary edema occurs when there are alterations in Starling forces and capillary permeability, opposition to lymphatic flow in the lungs, decreased plasma oncotic pressure, central nervous system lesions, and following some types of strenuous exercise. Pulmonary edema presents initially with crackles, wheezing, and dry cough and progresses to tachypnea, dyspnea, orthopnea, pink frothy sputum, and cyanosis. Treatment involves supportive therapy, reduction in blood volume, and oxygen therapy. PMID- 8000932 TI - Myocardial contusion: a case study of a myocardial infarction. AB - Injuries from blunt trauma can occur from a variety of causes. Myocardial contusion is the most common injury resulting from blunt, nonpenetrating trauma to the chest. The potential hemodynamic changes seen with a blunt chest trauma victim are often insidious and confusion. Diagnosing a myocardial contusion concomitant with other traumatic injuries can often be delayed, especially in light of the fact that immediate cardiac dysfunction may be slow in manifesting symptoms. Through use of a case study approach, this article demonstrates that a myocardial contusion has many similarities in terms of pathophysiologic changes with that of a myocardial infarction, often confusing symptoms and therefore diagnosis and treatment. PMID- 8000934 TI - Vasovagal syncope and head upright tilt table testing. AB - Syncope is a common medical complaint that is responsible for a significant number of emergency department visits and hospitalizations each year. A majority of syncopal events are believed to be caused by vasovagal responses. Although vasovagal syncope is essentially equivalent to simple fainting, the physiologic events that lead to this phenomena are complex. Although not completely understood, the most commonly held theory explaining vasovagal syncope involves a series of reflexive interactions between cardiac mechanoreceptors and the autonomic nervous system. Until the advent of head upright tilt table testing, diagnosis of vasovagal syncope has been an assumption, made when all other causes have been eliminated. Tilt table testing allows reproduction of the syncopal event in susceptible individuals and monitoring of the patients' physiologic responses during an episode. Direct observation and documentation of symptoms permit accurate diagnosis and yield information vital to treatment and symptom control. PMID- 8000935 TI - Two-year study of the prevention of unintentional extubation. AB - Unintentional or accidental extubation is an undesirable complication in the mechanically ventilated patient. This is particularly dangerous in high-risk patients who are on neuromuscular blocking agents or positive end-expiratory pressure or are difficult to reintubate. This article identifies some of the factors resulting in intentional extubation as well as measures taken to prevent them. A protocol was developed and utilized in Catholic Medical Center. The results of a two-year study reveal a reduction of the incidence from an initial 12% to 5% and a reduction of high-risk extubations from five to an incidence of three. The investigator also assembled an airway system consisting of low pressure cuff endotracheal tube with a pressure monitoring device and several adapters along with a tube fixation system. PMID- 8000937 TI - Pulmonary embolism after coronary artery bypass surgery. AB - Venous thromboembolism (VTE) is a well-recognized postoperative complication of major surgery; the frequency in patients undergoing coronary artery bypass graft surgery (CABG), however, has not been well established. Early recognition of the signs and symptoms of VTE after CABG may be delayed because of expected postoperative findings such as donor vein graft extremity edema, left hemidiaphragm paralysis, left pleural effusion, and left lower lobe atelectasis. Five of 120 patients (4.1%) who underwent CABG at one institution from July 1 to October 31, 1988 developed pulmonary embolism (PE). The diagnosis of PE was delayed in these 5 patients, 2 of whom (40%) died as a result of embolic disease. These patients demonstrate the difficulty in promptly diagnosing PE in the postoperative CABG period and illustrate the substantial clinical impact of PE in patients who have undergone CABG. PMID- 8000936 TI - Unplanned extubation in the intensive care unit: a quality-of-care concern. AB - A 1-month prospective quality improvement audit was performed to determine the incidence of self-extubation in the intensive care units (ICUs) at the Westchester County Medical Center (WCMC), a 625-bed tertiary care hospital with 92 intensive care beds in 11 ICUs. During the 1-month study period, there were seven unplanned extubations in six of 121 intubated patients, or one unplanned extubation for every 136 patient-ventilator days. Based on the initial review, a corrective action plan was initiated that consisted of education of nurses and house staff about the problem of unplanned extubation, daily assessment on rounds of patient risk of unplanned extubation, and careful documentation of any episodes of unplanned extubation. A 5-month follow-up review identified 12 unplanned extubations in 11 patients, which resulted in a reduced rate of one unplanned extubation per 455 patient-ventilator days. Risk factors for unplanned extubation included documented anxiety, routine care intervention, and a history of previous unplanned extubation. Unplanned extubation can be a serious complication associated with mortality and therefore is a quality-of-care concern. However, the majority of patients with this complication did well and were discharged from the hospital. The incidence of unplanned extubation can be reduced but not eliminated by a program of education and attention to risk factors for unplanned extubation. PMID- 8000938 TI - Significance of the insignificant. AB - This was an inductive descriptive study of supportive behaviors and sources of supportive behaviors in 20 critically ill, adult, pretransplant liver patients. Data were collected using a demographic tool and a semistructured interview schedule focusing on sources of support and supportive behaviors. Demographic data were analyzed by using frequencies, and interview data were analyzed utilizing content analysis. Participants were 28 to 68 years of age and considered themselves to be supported and critically ill. Family was mentioned most frequently as a support source. Supportive behaviors included visits, telephone calls, prayers, cards, and talking with the participants. Major themes from the interview data included family, spontaneous support, loss of supporters, encouragement, and the importance of the presence of someone else. Validation interviews were undertaken with a randomly drawn subset. Data underscore the differences in perception of important behaviors between health professionals and patients. Implications for practice are reviewed. PMID- 8000939 TI - Characteristics of the registered nurse and professional beliefs and decision making. AB - The study investigated various characteristics of registered nurses to estimate their influence on professional beliefs and decision making. The sample included 133 subjects who were predominantly female and white. The characteristics included age, years of practice, area of practice, level of education, certification, and membership to professional organizations. Results showed that professional beliefs and decision making were significantly related to level of education, membership to professional organizations, and certification. Employment of the analysis of variance showed that critical care nurses had the highest level of professional beliefs and decision making when compared with nurses in other areas of practice. Level of education area of practice, and certification were also predictive of professional beliefs and decision making. These results for the most part indicated that truly professional characteristics were related to professional beliefs and decision making, which reflected positively on the progress of the profession. PMID- 8000940 TI - The phenomena of nurses' caring behaviors as perceived by the critical care family. AB - Few studies have comprehensively focused on caring as perceived by the critical care family. This study explores and describes positive types of nurses' behaviors and critical care families' perceptions of these nursing behaviors as caring. Grounded theory methodology was used to enter the world of the critical care family and to elicit the meanings of caring behaviors in nurse-family interactions in the critical care waiting room. PMID- 8000941 TI - The effect of head covering on rewarming and shivering in cardiac surgical patients. AB - In hypothermic postoperative cardiac surgical patients, heat loss from the head may interfere with rewarming and cause shivering. This study investigated the effect of head covering on rewarming rate and shivering during post-operative rewarming. The sample included 19 experimental and 21 control subjects. The heads of experimental subjects were wrapped with two terry cloth towels until urinary bladder temperature (UBT) reached 37 degrees C. Admission UBTs were mildly hypothermic (34.6 degrees C to 36.70 C). Four experimental and six control subjects shivered. There were no significant differences (P < .05) in the incidence of shivering (Yates' chi 2 = 0.33; P = 0.855). After controlling significant differences between groups in height and body surface area with analysis of covariance, there were no significant differences in rewarming rate (F = 3.270; P = .079). Shiverers were slightly colder (mean, 36.13 degrees C; t = 1.768; P = .085) on admission to the cardiac surgical intensive care unit and had significantly greater heat gain (t = -2.091, P = .043) than nonshiverers. Conclusions about the effect of head covering on shivering could not be made because of small sample size. Failure to demonstrate a significant difference in rewarming rate is due to the effects of mildly hypothermic admission UBTs on the mathematical calculation of rewarming rate and on the small sample size. PMID- 8000942 TI - Chlorzoin. PMID- 8000943 TI - Surely our survival doesn't depend on sin? PMID- 8000944 TI - Neutropenia in childhood with oral manifestation--a case report. AB - Neutropenia is an unusual condition of blood dyscrasia in which the count of circulating neutrophils falls below the normal level. Neutrophil plays an important role in the host defense mechanism. The common clinical manifestations of neutropenia include ulcerative and inflammatory lesions in the oral cavity. A case of neutropenia of a seven-year-old girl is reported. PMID- 8000945 TI - A one-year statistical analysis of dental emergencies in a pediatric hospital. AB - Data on 1,373 emergency dental visits to a pediatric hospital during a calendar year period were reviewed. Chief complaints were categorized and the associated pathological conditions were identified and analyzed. A classification of pediatric dental emergencies is presented. PMID- 8000946 TI - Management of non-nutritive or digit-sucking habits in children--a practical approach. PMID- 8000947 TI - A simple and inexpensive resin-bonded bridge for the replacement of missing anterior teeth in the young patient. PMID- 8000948 TI - Ontario dentists: practice variation in referrals to pediatric dentists. AB - Variations in the pediatric referral practices of general dentists for children aged zero to 14 years may be related to issues concerning quality and standards of care, cost containment, and predictability in third-party payment programs. In September 1992, a survey mailed to a random sample of approximately 10 per cent of Ontario general dentists was used to gather information about pediatric referral practices as well as economic and demographic factors associated with these practices. Responses were received from 381 of the 540 dentists surveyed (69 per cent). Most dentists who gave reasons for pediatric referrals (85.6 per cent) named behavior management problems as the primary cause. However, 21.5 per cent did not refer any children under 14 to pediatric dentists. Due to the variable results obtained using assorted statistical tests to regrade the outcomes of interest, the self-reported nature of the data, and the large amount of pediatric referral practice variation left unexplained by the multivariate analysis (95 per cent), this study's findings are equivocal. PMID- 8000949 TI - [Paresthesia: incidence following the extraction of 455 mandibular impacted third molars]. AB - The incidence of paresthesia following the extraction of 455 mandibular impacted wisdom teeth is evaluated. No permanent paresthesia to the third branch of the trigeminal nerve is noted and no lingual paresthesia. A temporary dyesthesia of the inferior dental nerve is noted for three patients, with a complete return of integrity after six weeks. We have noted an incidence of temporary paresthesia of 3/455 (0.66 per cent) per tooth. PMID- 8000950 TI - Evaluation of competing tests for the diagnosis of pulmonary embolism and deep vein thrombosis, Part I. AB - Tests for pulmonary embolism (PE) and its most frequent source, deep vein thrombosis (DVT), include angiography, ventilation-perfusion nuclear medicine scans, venous sonography with Doppler, and contrast and radionuclide leg venography. Although selective angiography is the definitive procedure for the diagnosis of PE, the associated risk of death, although small, as well as the morbidity associated with injection of contrast agents, are high enough that alternative, less accurate, but safer diagnostic procedures are performed in an attempt to avoid the higher-risk procedure. Effective cost (EC) of each test represents the dollars spent per unit of diagnostic information and is defined as the ratio of the expected direct cost (EDC) of the test to its diagnostic performance (DU). EDC includes the base cost or charge of the test and the estimated cost of the morbidity and mortality that can be incurred in performing the test, while DU is determined from the test sensitivity and specificity. With the lowest EC as the selection criterion for the best test and representative costs, sensitivity, specificity, and morbidity and mortality rates, five different tests for PE or DVT were compared. Doppler sonography yielded the most diagnostic information per dollar spent, as its EC was the lowest, primarily because its base cost was low compared to that of the other tests. Radionuclide leg venography had the second lowest EC. Selection among the remaining three tests depended on the prevalence of PE and morbidity and mortality costs.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8000951 TI - Evaluation of competing diagnostic tests: sequences for the diagnosis of pulmonary embolism, Part II. AB - Tests for pulmonary embolism (PE) and its most frequent source, deep vein thrombosis, include angiography, ventilation-perfusion nuclear medicine scans, and contrast and radionuclide venography. Although selective angiography is the definitive procedure for diagnosis of PE, its risk of death, although small, as well as the morbidity associated with contrast injections, is high enough that alternative, less accurate but safer, diagnostic procedures are preferred. Part I of this report described the methodology for selection of the single test having the lowest effective cost based on the test cost, its risks, and diagnostic performance. Other than the pulmonary angiogram, however, no single test has a sufficiently high diagnostic performance to be clinically realistic: incorrect diagnoses can result in sudden death. Sequences of tests or algorithms can be used to lower the overall risk of the tests to patients while increasing correct decision making to reach a clinically acceptable level. These points are illustrated by comparing three commonly recommended algorithms for the diagnosis of PE. Additionally, the prevalence of PE affects the choice of the algorithm, and we found that no single algorithm is best for all values of prevalence. In summary, we found that the most cost-effective strategy was to select the particular algorithm having the lowest effective cost for the relevant prevalence value. Use of algorithms also decreased the overall risk of diagnostic test complications and the number of incorrect diagnoses. PMID- 8000952 TI - Capsular retraction of the liver in malignant tumor of the biliary tract MRI findings. AB - Retraction of the liver capsule adjacent to a hepatic tumor is an unusual feature that has received little attention in radiological literature. We report two patients with pathologically proved malignant tumor of the biliary tract (one cholangiocarcinoma and one gallbladder cancer) in whom magnetic resonance imaging (MRI) showed retraction of the liver capsule adjacent to the tumors. MRI was performed at 1.0 T, using a spin-echo (SE) technique, with T1 (TR/TE = 450/15 msec) and T2 (TR/TE = 2000/45 to 90 msec)-weighted images. Capsular retraction was seen on both T1- and T2-weighted SE MRI. Although capsular retraction of the liver adjacent to hepatic tumors is highly suggestive for epithelioid hemangioendothelioma, these two cases confirm that retraction of the liver capsule adjacent to hepatic tumors can be associated with other types of tumor, and especially with malignant tumors of the biliary tract. PMID- 8000953 TI - CT appearance of the normal and abnormal breast with mammographic correlation. AB - Mammography is the preferred technique to evaluate the breast but computed tomography (CT) performed for extramammary disease often images breast tissue. We reviewed studies of patients who underwent both CT and mammography to identify abnormalities that were visible with both techniques. The CT appearance of the normal breast, breast cancer, and several other abnormalities is demonstrated in this study. CT may occasionally allow for a precise diagnosis of a previously unsuspected breast lesion but a mammogram is usually required. PMID- 8000955 TI - Calcified medulloblastoma in a child. AB - Calcification is an unusual and atypical feature in medulloblastomas. Here we report a case of calcified medulloblastoma in a 5-year-old boy. The clinical correlation of this radiological finding is discussed. PMID- 8000954 TI - Chyloperitoneum: CT diagnosis. AB - We describe a patient with ovarian cancer in whom computed tomography revealed a fat-fluid level within ascites, indicating chyloperitoneum. The significance of this finding is discussed, and a mechanism underlying the unusual radiological appearance is suggested. PMID- 8000956 TI - Symptomatic leiomyoma of the adrenal. AB - Although small leiomyomas of the adrenal are a common incidental finding at autopsy, larger examples are extremely rare and have been asymptomatic, discovered as an incidental finding during computed abdominal scanning. We report the first, to our knowledge, instance of a large, symptomatic adrenal leiomyoma, and discuss the pathological and radiological features of the lesion. PMID- 8000957 TI - Splenic hemangioma. Detection on a technetium-99M MDP bone scan. AB - While relatively rare, the most common benign tumor of the spleen is the hemangioma. We report a case of a noncalcified splenic hemangioma found incidentally on a technetium-99m methylene diphosphonate (Tc-99m MDP) bone scan. Tc-99m MDP may have been accumulated by iron, which was deposited extensively within the hemangioma. PMID- 8000958 TI - Inflammatory pseudotumor of the liver. AB - We present a case of inflammatory pseudotumor of the liver (IPL), a rare benign hepatic lesion. A 66-year-old woman with fever, and right abdominal pain and mass underwent abdominal sonography and computed tomography. Both showed multiple hepatic masses. Ultrasound guided needle liver biopsy showed a dense chronic inflammatory lesion with innumerable foamy histiocytes and spindle fibroblasts consistent with IPL. She improved with conservative treatment. Clinical, pathologic, and imaging findings at IPL are reviewed. PMID- 8000959 TI - Vertebral body metastasis of glioblastoma multiforme with epidural mass formation. Contrast-enhanced MRI study. AB - A 35-year-old woman with left frontoparietal glioblastoma was subtotally resected twice and 1 year later demonstrated extracranial metastasis. Magnetic resonance imaging (MRI) demonstrated metastasis to the first thoracic vertebral body with epidural and paravertebral extension. Bone scintigrams of the spine appeared normal. The mechanisms and radiological findings of the extracranial metastasis of an astrocytic glioma are reviewed. PMID- 8000960 TI - Incidence of Norwalk virus infections during a prospective epidemiological study of drinking water-related gastrointestinal illness. AB - To determine the seroprevalence of Norwalk virus and whether Norwalk virus contributed to an observed increase in illness in tap water drinkers participating in a prospective epidemiological study, sera collected during the study were examined for changes in Norwalk virus antibody titer, using a specific enzyme immunoassay. Antibodies to Norwalk virus were measured in sera collected in March, June and September 1988 and in June 1989, and antibodies were found in 79% of the individuals. Seroprevalence increased with age, being 55% (ages 9-19), 79% (20-39), 87% (40-49), 84% (50-59), and 100% (60 and older). Norwalk infections occurred in 33% of the individuals during the course of the study. The highest rate of infection (expressed as a monthly rate) was observed during the summer of 1988. These results confirm that a large number of infections owing to Norwalk viruses occur throughout the year. A previous seroconversion or a high serum titer were not always protective. Finally, there was no detectable difference in infection rate between consumers of tap water and consumers of water treated by reverse-osmosis units, suggesting that Norwalk virus infections were not responsible for the excess of gastrointestinal illness observed in tap water drinkers during this epidemiological study. PMID- 8000961 TI - The optimization and application of two direct viable count methods for bacteria in distributed drinking water. AB - The optimal incubation conditions for the direct viable count method with nalidixic acid were determined. They do not differ from those proposed in the literature for a laboratory strain and a mixed bacterial population isolated from drinking water. The direct viable count method with 5-cyano-2,3-ditolyl tetrazolium chloride (CTC) was performed under in situ conditions. The bacteria were incubated with CTC at concentration of 1 mM for 4-6 h at the temperature of the water in the pipes and without the addition of an exogenous substrate. The results obtained for a laboratory strain using the two direct count methods were similar. However, for a mixed bacterial population, the counts were always higher with the CTC method than with the nalidixic acid method. PMID- 8000962 TI - Characterization of Aeromonas genomic species by using quinone, polyamine, and fatty acid patterns. AB - A chemotaxonomic study was carried out on representative strains of 13 Aeromonas genomic species. Quinone, polyamine, and fatty acid patterns were found to be very useful for an improved characterization of the genus and an improved differentiation from members of the families Enterobacteriaceae and Vibrionaceae. The Q-8-benzoquinone was the predominant ubiquinone, and putrescine and diaminopropane were the major polyamines of the genus. The fatty acid patterns of 181 strains, all characterized by DNA-DNA hybridization, showed a great homogeneity within the genus, with major amounts of hexadecanoic acid (16:0), hexadecenoic acid (16:1), and octadecenoic acid (18:1), and minor amounts of the hydroxylated fatty acids (3-OH 13:0, 2-OH 14:0, 3-OH 14:0) in addition to some iso and anteiso branched fatty acids (i-13:0, i-17:1, i-17:0, and a-17:0). Although some differences in fatty acid profiles between the genomic species could be observed, a clearcut differentiation of all species was not possible. PMID- 8000963 TI - Effect of cultural and nutritional conditions on the control of flocculation expression in Saccharomyces cerevisiae. AB - The effect of cultural (temperature and pH) and nutritional conditions (nitrogen and carbon source) on the flocculation expression of three strains was studied. The strains' flocculation ability was determined by placing the cells in a stationary phase of growth in standard flocculation conditions. The flocculation ability of strain NCYC 1195, recently classified in the literature as the NewFlo phenotype, was more sensitive to growth temperature than Flo1 phenotype strains (NCYC 869 and NRRL Y265). The initial pH of the culture medium did not affect the flocculation ability of Flo1 phenotype strains but in the case of strain NCYC 1195 flocculation was repressed when the initial pH of the culture medium was below 3.5. Flocculation in strain NCYC 1195 was also repressed in defined culture medium; this inhibition was not related to a deficiency in any particular nitrogen source, but rather to the poor buffering capacity of the defined medium. All strains showed strong flocculation when grown in glucose, but were nonflocculent in glycerol. It was clearly demonstrated that the phenotypic expression of flocculation could be induced or repressed by changing cultural and nutritional conditions. Two distinct behaviours were also displayed with regard to the effect of the cultural conditions upon flocculation, namely the effect of pH. These different behaviours can be used to distinguish the two flocculation phenotypes. PMID- 8000964 TI - Presqualene metabolism in two species of Lagenidium. AB - The fate of precursors of the isoprenoid pathway was studied in the sterol auxotroph Lagenidium giganteum and in the positive control organism Lagenidium callinectes. Acetate derived from glucose and mevalonic acid was converted to sterols and fatty acids in L. callinectes. Lagenidium giganteum converted mevalonic acid to sterols and fatty acids, but glucose-derived acetate was not utilized for sterol synthesis. The results showed that the defect in the isoprenoid pathway of L. giganteum occurs at the level of the beta-hydroxy-beta methylglutarylcoenzyme A reductase-synthase complex. Various aspects of this defect are discussed relative to metabolism of the organism. PMID- 8000965 TI - Adherence of Legionella pneumophila to U-937 cells, guinea-pig alveolar macrophages, and MRC-5 cells by a novel, complement-independent binding mechanism. AB - In the absence of serum, Legionella pneumophila demonstrated wash-resistant adherence to U-937 cells, primary guinea-pig alveolar macrophages, and MRC-5 cells. Neither complement nor antibody was required for binding. The dynamics of adherence following inoculation of L. pneumophila at increasing 10-fold multiplicities of infection to each of the three host cell types resulted in a first-order kinetic relationship of binding, indicative of one bacterial adhesin molecule recognized by one host cell receptor moiety. Host cell receptor saturation studies showed that depending on the cell type, 2-8% of the bacterial inoculum adhered to cells under these nonopsonic conditions. Preliminary adhesin and receptor characterization studies were performed to define the chemical composition of the binding structures on both the organism and the three different host cell surfaces. The adherence phenomenon was investigated using competitive binding assays in the presence of putative adhesin analogs as well as following treatments modifying the microbial and host cell surface membranes. Attachment was evaluated both by viable bacterial cell colony counts and by indirect immunofluorescent assay. With the exception of aldehyde treatments, the various membrane-modifying regimes and the presence of the adhesin analogs were shown to have no effect on organism or host cell viability. Data suggested that the L. pneumophila adhesin responsible for opsonin-independent binding to these host cells was a protein structure with lectin-like properties. Furthermore, this protein would appear to be intimately associated with carbohydrate or lipid structures located on the bacterial outer membrane.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8000966 TI - Expression of the symbiotic plasmid from Rhizobium leguminosarum biovar trifolii in Sphingobacterium multivorum. AB - An inoculant strain of Rhizobium leguminosarum biovar trifolii containing a Tn5 marked symbiotic plasmid transferred this plasmid by conjugation to Sphingobacterium multivorum, an organism that can be found in soil. The transconjugant bacteria nodulated the roots of white clover (Trifolium repens) seedlings but did not fix atmospheric nitrogen. Microscopic examination revealed abnormal nodule structures. Bacteria isolated from the nodules were shown to be closely related to the recipient S. multivorum and Southern blots of genomic digests probed with nodA DNA confirmed that the transconjugants contained symbiotic genes. This is the first report of the spontaneous transfer, by conjugation, of a symbiotic plasmid from R. leguminosarum biovar trifolii to S. multivorum. PMID- 8000967 TI - Cryptococcus neoformans infection can elicit protective antibodies in mice. AB - An IgG1 monoclonal antibody generated from a mouse infected with Cryptococcus neoformans modified the course of intravenous cryptococcal infection in A/J mice by prolonging survival and reducing lung fungal burden, brain mass, and serum polysaccharide levels. The results demonstrate that C. neoformans infection can elicit useful antibodies. PMID- 8000968 TI - Cognitive side effects of antiepileptic drugs. AB - All of the established antiepileptic drugs (AEDs) can produce cognitive side effects, which are increased with polypharmacy and with increasing dosage and anticonvulsant blood levels. However, cognitive side effects are usually modest for AED monotherapy with anticonvulsant blood levels within the standard therapeutic ranges. Further, these effects are offset in part by reduced seizure activity. Controversy exists regarding possible differential cognitive effects of AEDs. A large portion of the literature examining the comparative cognitive effects of AEDs is limited by inadequate study designs. When these design flaws are considered, there is no convincing evidence of clinically significant differences in cognitive side effects of AEDs except possibly for bromide, phenobarbital and benzodiazepines. The role of cognitive side effects should be kept in proper perspective when choosing AED therapy. The cognitive side effects of anticonvulsant drugs may be overt but many times are rather subtle. It is important though to be able to recognize these effects and to put them into perspective as to how they affect our patients. PMID- 8000969 TI - How about the new antiepileptic drugs? AB - No new antiepileptic drugs (AEDs) were licensed in the United States from 1978 to 1992. In late 1992, felbamate and gabapentin were recommended for approval, and in early 1993, lamotrigine. In July 1993, felbamate was licensed, and gabapentin and lamotrigine may soon follow. Lamotrigine, vigabatrin and clobazam are in use outside the US. Tiagabine, oxcarbazepine, fosphenytoin, topiramate, vigabatrin and zonisamide are in Phase II clinical testing in the US. All of the new AEDs are effective against partial and tonic-clonic seizures. Few controlled clinical trials have been done in patients with absence and myoclonic seizures. Mechanisms of action of the new drugs have not been clearly defined. The new AEDs will provide an opportunity to improve the care of epileptic patients. Even with optimal management with currently available drugs, some 30% of patients remain refractory to medical management. PMID- 8000970 TI - Antiepileptic drug selection and adverse effects: an overview. AB - In choosing an antiepileptic drug, not only efficacy but also potential adverse effects have to be considered. Adverse effects that have to be taken into account include acute and chronic systemic toxicity, cognitive side effects, and teratogenesis. Acute toxicity may be dose-related, allergic or an idiosyncratic reaction. Chronic toxicity may involve the nervous system or other organs. In determining the role of new antiepileptic drugs such as lamotrigine, vigabatrin, felbamate, and gabapentin a proper evaluation of both efficacy and adverse effects is required. PMID- 8000971 TI - Acute and chronic toxicity of antiepileptic medications: a selective review. AB - Acute and chronic toxicity complicates all antiepileptic medications (AED) and is idiosyncratic. Acute toxicity can be categorized into 1) acute brain dysfunction or 2) acute organ dysfunction when AED's are started. Despite promising in vitro lymphocyte testing, anticipation of acute reactions cannot be offered. Furthermore, screening for AED toxicity by routine blood and urine tests in asymptomatic patients is of doubtful value and should be abandoned. Patients should be informed of possible reactions and immediately report early symptoms. Treatment for acute reactions is largely unstudied. It is unclear how to reintroduce AED's following acute reactions. Often patients are sensitive to drugs with a similar chemical structure. The "desensitization" protocol of Purvis may be of merit. Three major chronic toxicities of AED's have been noted--soft tissue and gum hypertrophy, progressive ataxia, and peripheral neuropathy. New AED's require careful post-marketing surveillance since long term toxicity data are not yet available. PMID- 8000972 TI - Richardson Lecture. Adaptive control of eye movements: clinical implications. AB - This paper is directed primarily to clinicians who diagnose and treat patients with neurological disorders. It is an attempt to illustrate that even with modern imaging technology and other advances in laboratory testing, a thorough understanding of neurophysiology and its anatomical substrate still plays an important role in the diagnosis and management of patients with neurological diseases. One area in neurophysiology in which there has been great progress in the last few decades is the ocular motor system. Particular interest has been focused on the ways that the brain can adapt to lesions, and more specifically, how the ocular motor system keeps itself calibrated in the face of normal development and aging as well as in response to disease and trauma. Since disorders of eye movements are such common and often dramatic manifestations of neurological disease it seems appropriate to bring some of the newer concepts in ocular motor physiology to the "bedside". PMID- 8000973 TI - The place of neuronal migration abnormalities in child neurology. AB - With the development of modern imaging techniques, disturbances of neuronal migration appear to be a major cause of epilepsy, mental retardation and chronic neurological disability in childhood. Sixty-nine cases are presented, including 46 of diffuse migration abnormalities and 23 of localized dysplasia. Patients with diffuse migration disorders presented with mental retardation, gross motor impairment and severe seizure disorders whereas in those with focal anomalies, epilepsy was the chief complaint. Magnetic resonance imaging, although usually diagnostic of migration disorders often does not allow definition of the pathologic type. Some EEG patterns, such as high amplitude fast rhythms or the theta-delta pattern are highly suggestive. Most cases of abnormal migration are sporadic and probably acquired. Some are due to chromosomal anomalies, especially of chromosome 17p where a gene for lissencephaly has been mapped. Familial cases occur with both recessive and possibly dominant inheritance. Epilepsy due to migration abnormalities is often intractable. Resection of dysplastic cortex may be effective for localized disease and callosotomy has been proposed for diffuse anomalies. PMID- 8000974 TI - The influence of sulindac on experimental streptozotocin-induced diabetic neuropathy. AB - We studied the influence of sulindac, a nonsteroidal anti-inflammatory agent on experimental streptozotocin-induced diabetic neuropathy. Untreated diabetic rats were compared with nondiabetic rats, diabetic rats treated with low dose insulin and diabetic rats given sulindac (6.0 mg/kg by gavage 5 of 7 days weekly). Neuropathy was assessed by following serial in vivo motor and sensory caudal conduction, resistance to ischemic conduction failure, and in vitro conduction in sural myelinated and unmyelinated sensory fibers. The impact of low dose insulin and sulindac treatment on the microenvironment of the L4 dorsal root ganglion and sciatic endoneurium was assessed by measuring local perfusion and oxygen tension after 16 weeks of diabetes. Sulindac normalized conduction velocity in caudal sensory fibers, sural myelinated fibers and sural unmyelinated fibers, and reduced the number of diabetic cataracts. Sulindac also normalized a deficit in dorsal root ganglion blood flow and a reduction in sciatic endoneurial oxygen tension in diabetic rats. Low dose insulin improved neuropathy as well but the pattern of benefits was less robust than that of sulindac. Sulindac may be a candidate for a clinical trial in human diabetic polyneuropathy. PMID- 8000975 TI - Autosomal recessive, fatal infantile hypertonic muscular dystrophy among Canadian Natives. AB - We describe eleven mid-western Canadian aboriginal infants with a unique, progressive muscle disorder. All except one had muscle biopsy and/or autopsy. The infants were normal newborns who rapidly developed rigidity of all skeletal muscles, with early, respiratory insufficiency. Death occurred before 18 months of age. Electromyography showed increased insertion activity and profuse fibrillation potentials; motor unit potentials and interference pattern are normal until late in the course. Pathologic features include progressive, granular to powdery Z-band transformation, myofibrillar loss, and muscle regeneration. SDS-gel electrophoresis of one muscle sample revealed increased 54kDa and reduced 80kDa protein fractions. This disease differs from other conditions with Z-band alterations because of continuous muscle activity and relentless clinical progression. The clinical features, elevated serum creatine kinase, electromyographic and muscle biopsy findings suggest a dystrophic process. The recognition of this condition as an autosomal recessive disorder allows appropriate genetic counselling. PMID- 8000976 TI - Complications of first craniotomy for intra-axial brain tumour. AB - Complications were examined in a single surgeon's series of 207 consecutive adult patients undergoing first craniotomy for intra-axial brain tumour. The study group consisted of 114 gliomas, 74 metastatic tumours and 19 miscellaneous lesions. There were 25 infratentorial tumours and 182 supratentorial tumours (39 deep and 143 superficial). The total number of patients sustaining complications was 52 for an overall complication rate of 25.1%; the rate was higher for infratentorial tumours (44.0%) than supratentorial tumours (22.8%) regardless of histology (p = 0.012). There were 5 deaths for a mortality rate of 2.4%. Forty seven patients incurred operative morbidity (22.7%); 7 out of the 47 had multiple complications. Sixteen patients sustained transient worsening due to edema (7.7%) and 6 patients sustained permanent neurological deficit (2.9%). Medical complications were suffered by 17 patients (8.2%). Major complications which significantly altered the quality and/or quantity of survival were suffered by 9 patients overall (4.3%). PMID- 8000977 TI - Somatosensory evoked potentials and intracranial pressure in severe head injury. AB - The purpose of this study was to explore the relationship between neurologic function, using a quantitative measurement of continuous somatosensory evoked potentials (SSEPs), and intracranial pressure (ICP) following traumatic brain injury. During a 6 year period, severely head-injured patients with a Glascow Coma Scale < or = 8 who were not moribund were monitored with SSEPs and ICP measurements. SSEPs from each hemisphere and ICP were recorded hourly for each patient. Neurologic outcomes were scored using the Glasgow Outcome Scale at three months post injury. Although initial SSEP amplitude did not correlate well with outcome, final SSEP summed peak to peak amplitude from both hemispheres (p = .0001), the best hemisphere (p = .0004), and the worst hemisphere (p = .0001) correlated well with the Glasgow Outcome Scale groups. Of a total of 72 patients, 40 had deteriorating SSEPs and 32 had stable or improving SSEPs. Peak ICP values were not statistically different in these groups (p = .6). Among patients with deteriorating SSEPs, 52.5% lost the greatest proportion of hemispheric electrical activity prior to ICP elevation. In the remaining patients, the percent reduction of SSEP activity after peak ICP levels was not statistically different from the percent reduction in SSEP activity prior to the peak ICP levels (p = .9). This data suggests that in a select group of patients with severe head injury, ICP does not cause SSEP deterioration, but rather is the consequence of deterioration of brain function. PMID- 8000978 TI - NMDA receptor blockade and spinal cord ischemia due to aortic crossclamping in the rat model. AB - Recent brain research proposes that, during ischemia, synaptically released excitatory amino acid neurotransmitters accumulate at toxic concentrations with ensuing neuronal death. Their action is mediated by the receptor subtype N-methyl D-aspartate (NMDA). The protective effect of NMDA receptor blockade with intrathecal MgSO4 and MK-801 was investigated during spinal cord ischemia induced by aortic occlusion of 12 minutes. Male Sprague-Dawley rats, 250-300g, underwent intrathecal administration of 20 microL of normal saline (SA n = 16), MgSO4 1M (MG n = 16), or MK-801, 25 mM solutions (MK n = 16) in a randomized order. After 2 hours, the animals underwent occlusion of the thoracic aorta and subclavian arteries for 12 min. An additional control group (CO n = 16) underwent occlusion for 12 minutes, without intrathecal injection. The animals were scored according to their functional performance (LS = lesion score) each day for four days by a blinded observer. Mean LS were calculated for each group at a given day. Treatment and control groups were not different at day 1 (P = 0.302). Group MG was improved from groups SA (P = < 0.0039) and CO (P = < 0.0048) at day 4. This study demonstrates that although intrathecal NMDA receptor blockade with MgSO4 or MK-801 does not prevent paraplegia due to spinal cord ischemia in the rat, it could however influence the rate of recovery after ischemic injury. PMID- 8000980 TI - Assessment of genetic polymorphisms in DNA from formalin fixed neurological tissues. AB - The ability to analyze the genotype of deceased affected members of pedigrees segregating inherited neurological diseases considerably augments the informativeness of such pedigrees. This information has direct application in attempts to isolate disease genes by positional cloning strategies, and for genetic counselling. We show that the genotype at polymorphic simple sequence repeat loci can be determined from genomic DNA isolated from 10 micron thick paraffin embedded, formalin fixed neurological tissues. The critical constraint on this method is the size of the template target bearing the simple sequence repeat, which should ideally be less than 165 base pairs. PMID- 8000979 TI - Large unresponsive zones appear in cat somatosensory cortex immediately after ulnar nerve cut. AB - The organization of the primary somatosensory cortex innervated by the ulnar nerve was studied before and immediately after ulnar nerve transection in 11 cats electrophysiologically mapped under Nembutal or Ketamine anesthesia. The cortex was reexamined a second time beginning 42 hr after nerve transection in four cats anesthetized with Nembutal. One additional sham-operated control was also mapped. The region of cortex formerly served by the ulnar nerve remained largely unresponsive to somatic stimulation independent of the type of anesthetic used during recording. Nonetheless, animals anesthetized with Ketamine had more new responsive sites in deafferented cortex following nerve cut than cats anesthetized with Nembutal. New responses, when observed, were evoked by stimulation of a region of skin adjacent to the region served by the ulnar nerve. These findings suggest that the immediate response to deafferentation of somatosensory cortex is a limited acquisition of novel responses restricted to a region immediately adjacent to cortex containing normal afferent input. PMID- 8000981 TI - Ataxia in institutionalized patients with epilepsy. AB - Fifty-four per cent of 41 chronically institutionalized adult patients with epilepsy had ataxia of gait (wide mean stride width). None of the following correlated with stride width: serum phenytoin, previous phenytoin toxicity, seizure frequency, or status epilepticus. Seventeen of the 41 patients had computed tomographic head scans. Patients with radiological evidence of cerebellar atrophy had a wider mean stride width, later age of onset of seizures, greater peak serum concentrations of phenytoin than did those without cerebellar atrophy. Ataxia of gait was inconsistently associated with cerebellar atrophy. Elevated serum/plasma concentrations of phenytoin may be a risk factor for cerebellar atrophy, but seizure frequency or status epilepticus are not independently related to this complication. PMID- 8000982 TI - Fluoxetine and selegiline--lack of significant interaction. AB - The use of the combination of fluoxetine, an anti-depressant serotonin uptake inhibitor, and selegiline, a monoamine oxidase -B inhibitor, was reviewed in a large population of patients with Parkinson's disease. All records were reviewed from a Parkinson's disease clinic to determine how many patients were treated simultaneously with selegiline and fluoxetine. Patient characteristics, duration and dose of treatment, side effects and reasons for discontinuation were noted. Twenty-three patients received both medications at the same time. No additional side effects were noted with the combination therapy that had not already been reported with each medication alone. No serious side effects were found. In this clinic population, fluoxetine and selegiline were used in combination without major side effects, but further observation is warranted. PMID- 8000983 TI - A prevalence study of multiple sclerosis in the Crowsnest Pass region of southern Alberta. AB - Reports of a high prevalence rate for multiple sclerosis in Southern Alberta led to an epidemiologic study of this disease in the Crowsnest Pass and Cardston regions. In Cardston, the prevalence rate for multiple sclerosis was 88 per 100,000. In the Crowsnest Pass, the prevalence rate was 217 per 100,000. Previous epidemiologic studies of the prevalence rate of multiple sclerosis in Western Canada have shown rates between 93 and 111 per 100,000. Two prevalence studies of multiple sclerosis in Barrhead County, Alberta and Westlock County, Alberta show prevalence rates of 196 and 201 per 100,000. The prevalence rate in the Crowsnest Pass is comparable to the prevalence in Barrhead County and Westlock County, Alberta. However, there is no statistically significant difference between prevalence rates in the Cardston and Crowsnest Pass regions and our overall feeling is that the results of studies of small populations should be interpreted with caution. PMID- 8000984 TI - A controlled trial of mitoxantrone in multiple sclerosis: serial MRI evaluation at one year. AB - We present the results of a randomized double-blinded placebo controlled, multicenter trial, of low-dose mitoxantrone (MX), after one year, in 25 patients with relapsing-remitting multiple sclerosis, who had serial enhanced magnetic resonance imaging (MRI). Treatment groups were balanced for age, gender, duration of illness and neurological disability. Five of the 13 MX patients and 10 of the 12 placebo patients had exacerbations during treatment (p < 0.02). The mean change in the extended disability status scale was not significantly different between the MX and placebo treatment groups. Serial Gadolinium-DTPA enhanced MRI detected no significant difference between the MX treated and placebo groups in the mean total number of new, enlarging, or Gadolinium-DTPA enhancing lesions; there was a trend toward a reduction of new, enlarging and Gadolinium-DTPA enhancing lesions in MX patients. Despite this ameliorating effect, the results indicate that serial Gadolinium-DTPA enhanced MRI, performed over one year in a limited number of patients, could not provide conclusive evidence for a role of MX therapy in relapsing-remitting multiple sclerosis. PMID- 8000985 TI - Intractable hiccup due to multiple sclerosis: MR imaging of medullary plaque. AB - We describe a 31-year-old man with clinically definite multiple sclerosis who presented with intractable hiccup for one month prior to admission. The responsible lesion was confirmed by magnetic resonance imaging to be a plaque in the ventral paramedian portion of the medulla oblongata. PMID- 8000986 TI - Malignant rhabdoid tumour of the pineal region. AB - A 9-month-old male presented to hospital with signs and symptoms of raised intracranial pressure. A CT scan showed obstructive hydrocephalus from a large pineal region mass lesion into which an intratumoral hemorrhage had occurred. A posterior fossa craniectomy and subtotal excision of the mass lesion were performed. By histopathology, the lesion was a malignant rhabdoid tumour (MRT). Despite surgery and chemotherapy, the tumour grew inexorably, and the patient died four months after the initial diagnosis. MRT is a rare and highly invasive neoplasm which infrequently arises from the central nervous system. This is the first documented case of a MRT arising from the pineal region. The clinical, radiographic, and pathological features of the MRT in this patient are presented. PMID- 8000987 TI - Neurosurgery at the Toronto General Hospital, 1924-1990: Part 2. PMID- 8000988 TI - MOCOMP: an idea whose time has come for Canadian neurology. PMID- 8000989 TI - Neuropathologists: another byproduct of neurosurgery at the Toronto General. PMID- 8000990 TI - Neuropathologists: another byproduct of neurosurgery at the Toronto General. PMID- 8000991 TI - Histology of cancer incidence and prognosis: SEER population-based data, 1973 1987. Dedicated to Dr. Harold L. Stewart. PMID- 8000992 TI - Cancer. Introduction. AB - This supplement presents the study of various histologic types of cancers diagnosed in the populations covered by the Surveillance, Epidemiology, and End Results (SEER) Program. It describes the SEER program and the coding of histologic type by the International Classification of Diseases for Oncology. Each of the 19 articles deals with the histologic types of cancer found in major sites or with specific histologic types, such as lymphomas or melanomas. Histologic types have been grouped based on those developed by Dr. John Berg. Data presented in this supplement are based on more than one million microscopically proven invasive cancers and 98,000 in situ cancers diagnosed during the period 1973-1987 in areas covered by the SEER Program. PMID- 8000993 TI - Upper aerodigestive tract cancers. AB - BACKGROUND: Cancers of the upper aerodigestive tract constitute approximately 4% of all malignancies. These include cancer of the lip, tongue, major salivary glands, gums and adjacent oral cavity tissues, floor of the mouth, tonsils, oropharynx, nasopharynx, hypopharynx and other oral regions, nasal cavity, accessory sinuses, middle ear, and larynx. METHODS: The histologically diagnosed cancers of the upper aerodigestive tract reported to the Surveillance, Epidemiology, and End Results program of the National Cancer Institute in 1973 1987 were tabulated by histologic type, sex, age, and racial group, and according to quinquennium (1973-1977, 1978-1982, 1983-1987). Frequencies, age-specific incidence rates, median age, and extent of spread at diagnosis, stage, and survival were examined. RESULTS: Cancer of the upper aerodigestive tract represented 3.5% of all microscopically proven malignant neoplasms. Except for salivary glands, gums, nasopharynx, and nasal cavity and accessory sinuses, epidermoid carcinomas accounted for greater than 95% of the cancers. For all aerodigestive sites combined, there was a 2-to-1 male-to-female ratio (greater for laryngeal cancer, which was approximately 5 to 1). Incidence in black males was often twice the levels recorded in white males, whereas rates for black and white females tended to be close. The 5-year relative survival was approximately 50% (90% for lip and 65% for larynx), was somewhat better for whites than for blacks, and did not improve significantly over the 15 years studied. Salivary gland adenocarcinoma carried a survival of approximately 80%. CONCLUSIONS: Because many of the cancers of the upper aerodigestive tract are caused by alcohol and tobacco use, the potential for prevention is considerable. PMID- 8000994 TI - Gastrointestinal cancer. AB - BACKGROUND: There are great differences in incidence and prognosis of cancer among the component sites of the digestive tract. Furthermore, a number of the histologic types of tumors at these sites differ in their incidence and prognosis. METHODS: The SEER data from 1973 to 1987 on frequency, incidence, staging, and survival for the various histologic types of 194,452 cancers of the esophagus, stomach, and intestines were studied. RESULTS: There was an increased incidence of adenocarcinomas of esophagus, gastric cardia, small intestine, and colon; incidence rates for rectal adenocarcinoma and esophageal squamous cell carcinoma remained stable; and rates for gastric adenocarcinoma decreased. Blacks had higher incidence rates than whites for gastric adenocarcinoma; squamous cell carcinoma of the esophagus; carcinoids of the small intestine, colon, and rectum; and gastric sarcomas. Whites, especially males, had higher incidence rates for adenocarcinomas of the esophagus and gastric cardia than did blacks. Blacks had lower rates for rectal adenocarcinomas than did whites, but slightly higher rates than whites for rectal mucinous carcinomas and colonic adenocarcinomas. Data on race, sex, survival, and time trends indicate that mucinous colorectal carcinomas are biologically different from other adenocarcinomas. Males had poorer overall survival than did females for most histologic types of digestive tract tumors. Appendiceal mucinous adenocarcinomas with distant metastases were associated with a high (50%) 5-year survival. The poor prognosis of cases diagnosed as colonic carcinoid raises the possibility that some of these actually may be carcinomas. CONCLUSION: Studies of digestive tract cancer require analysis by histologic type for adequate assessment. PMID- 8000995 TI - Liver, gallbladder, extrahepatic bile ducts, and pancreas. AB - BACKGROUND: The liver, gallbladder, bile ducts, and pancreas have a common embryologic origin; cancers that arise from these sites therefore are expected to share a similar spectrum of histologic types. These cancers are known for their extremely poor prognoses. METHODS: Data from the Surveillance, Epidemiology, and End Results Program regarding the incidence, distribution of histologic types, stage of disease, and survival for cancers of the gallbladder (n = 4412), extrahepatic bile ducts (n = 3486), pancreas (n = 23,116), and liver (n = 6,391) were reviewed. The most common histologic types are discussed, and the frequency of rare types is reported. RESULTS: The incidence of biliary cancer decreased, while the incidence of hepatic and pancreatic cancer rose slightly over the 15 year period from 1973 to 1987. Age and sex distributions varied by histologic type. Greater than 98% of pancreatic and biliary cancers were carcinomas, and adenocarcinoma (not otherwise specified) was the most common histologic type recorded. In the liver, hepatocellular carcinoma was the most common type, followed by intrahepatic cholangiocarcinoma. The overall 5-year relative survival rates for these cancers were very low: gallbladder, 12.3%; extrahepatic bile duct, 12.7%; liver 3.1%; and pancreas 2.5% (all stages combined, 1978-1986). CONCLUSIONS: This review confirmed that these carcinomas are associated with a very poor outcome; however, survival was influenced by stage of disease and histologic type. In the gallbladder and extrahepatic bile ducts, papillary adenocarcinoma was associated with the best outcome of all histologic types, and in the exocrine pancreas, mucinous cystadenocarcinoma was associated with the best prognosis. PMID- 8000996 TI - Lung cancer. AB - BACKGROUND: Lung cancer is the most common cause of cancer death in the United States, and its incidence has been rising for at least 50 years. Shifts in histologic type and differences in sex and race distribution have accompanied the increased incidence of lung malignancies. METHODS: Population-based data regarding lung cancer reported to the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) program for the 15-year period 1973-1987 were analyzed. RESULTS: Results indicate that from 1973-1977 to 1983-1987, the age-adjusted rates of lung cancer increased by 30%, with the gain markedly greater in women (70%) than in men (17%). The largest percentage increases in age adjusted rates were observed for small cell carcinoma and adenocarcinoma (approximately 60% each), with a more modest change for squamous cell carcinoma (+ 14%). For squamous cell carcinoma, the age-adjusted rates increased substantially for black (65%) and white (70%) women and only slightly for black men (10%), whereas it decreased slightly in recent years for white men. CONCLUSIONS: In recent years, adenocarcinoma has replaced squamous cell carcinoma as the most frequent histologic subtype for all sexes and races combined. These shifts in histologic types by sex and race may be related to differences in exposure to tobacco products, dietary factors, environmental or occupational carcinogens, and host characteristics. Increased use of transbronchial and needle biopsy may have also influenced these trends to some extent. Over the study period, 5-year relative survival rate did not change appreciably for lung cancer, suggesting that therapeutic advances have had little effect. PMID- 8000997 TI - Bone cancers. AB - BACKGROUND: Frequency distribution data for primary bone sarcomas have long been used to provide clues to the diagnosis of bone cancers after their identification in radiographs. Age and skeletal site are often helpful, in addition to specific radiographic features, in narrowing down the probable histologic categories of bone neoplasms before biopsy. METHODS: Data on 2627 histologically confirmed primary malignant tumors of bone, as collected by the SEER program during the period 1973-1987, were analyzed by age, sex, race, and anatomical site. RESULTS: Osteosarcoma was the most frequently diagnosed primary sarcoma of bone (35.1%), followed by chondrosarcoma (25.8%), Ewing's sarcoma (16.0%), chordoma (8.4%), and malignant fibrous histiocytoma, including fibrosarcoma (5.6%). The most frequently diagnosed sarcoma of bone in persons younger than age 20 was osteosarcoma, followed by Ewing's sarcoma. Chondrosarcoma was the most frequently diagnosed bone tumor in the population older than age 50. The overall 5-year relative survival rates were as follows: osteosarcoma, 41.0%; chondrosarcoma, 72.7%; Ewing's sarcoma, 41.2%; chordoma, 63.8%; and malignant fibrous histiocytoma, 42.9%. There was an improvement in the survival rates during the period 1973-1987 for patients with chordoma and for white female patients with Ewing's sarcoma. Ewing's sarcoma and chordoma occurred almost exclusively in the white population. CONCLUSIONS: SEER data provide a unique opportunity to evaluate the incidence and survival rates of bone sarcomas, which are uncommon but highly lethal tumors. The findings from this analysis provide information useful in the diagnosis of these cancers. PMID- 8000998 TI - Sarcomas and other malignancies of soft tissue, retroperitoneum, peritoneum, pleura, heart, mediastinum, and spleen. AB - BACKGROUND: Malignant neoplasms of the structural tissues, consisting mostly of soft tissue sarcomas, are morphologically diverse and rarely treated for epidemiologic purposes as individual entities. Our understanding to date of the pattern of occurrence of sarcomas is based largely on reports of limited individual clinic experience or case-control studies, each driven by a single hypothesis, and there have been virtually no descriptions according to specific morphologic type. METHODS: The accumulated coverage of the SEER populations offers an opportunity to correct this deficit. Each of the diagnoses has been reported and coded using a single set of rules and described in relation to the population at risk in terms of age, sex, race, calendar period, anatomic location, and outcome. In addition, each morphologic type has been compared with each of the others with respect to the pattern of occurrence and survival. RESULTS: For most of the individual morphologic entities, the pattern of occurrence is specific and unlike other patterns. Differences according to anatomic site, age, sex, race, and period-specific survival were found. Partly because of changes in diagnostic criteria over the years, differences in secular trend, other than that for Kaposi's sarcoma, could not be verified. Although some types of sarcoma may have important genetic determinants, there is evidence of environmental causation in others; for some varieties both genetic and environmental factors may operate. There is no evidence of improvements in survival. CONCLUSIONS: The most likely basis for the observed patterns are morphology-specific differences in etiology and growth phase. Each of the entities should be considered etiologically distinct and should be studied individually whenever possible. PMID- 8000999 TI - Skin cancer. Melanoma and other specific nonmelanoma skin cancers. AB - BACKGROUND: Malignant melanoma accounts for most of the growing mortality from skin cancer. However, survival rates are increasing for individual cases, probably because of earlier diagnoses. METHODS: Skin cancers collected by the SEER population-based data base between 1973 and 1987 are described in terms of their histologic classification and their distribution by sex, race, anatomical location, geographic locality, and time period of occurrence. RESULTS: There were 30,519 invasive skin cancers in the 15-year reporting period. Because the common basal cell and squamous cell cancers are not reportable to SEER, most of the cancers (28,206) were melanomas. In addition, 4386 in situ melanomas were reported. The rate of melanoma was 13-fold higher in whites than in blacks and 29% higher in white males than in white females. There was a 52% increase in the age-adjusted incidence rate for invasive melanoma and a 600% increase in the incidence rate of in situ melanoma over the 15-year period for whites and a 12% decrease in the incidence rate of invasive melanoma in blacks. The incidence of melanoma in the ear and trunk predominated in males, whereas melanoma of the lower limb predominated in females. Incidence rates and rate of increase of incidence of melanoma varied by anatomical subsite, sex, and geographic location within the United States. CONCLUSIONS: The variations among incidence rates of melanoma by sex, subsite, race, geographic location, and time period support prevailing theories of a solar cause for most but not all cases of this disease. Although melanoma rates are rising overall, the disproportionate rise in the rate of diagnosis of in situ compared with invasive melanoma suggests that melanomas are being diagnosed earlier. PMID- 8001000 TI - Breast cancer. AB - BACKGROUND: Breast cancer is the most common cancer and the second leading cause of cancer death among women in the United States; annual breast cancer deaths are exceeded only by those for lung cancer. METHODS: Data from the Surveillance, Epidemiology, and End Results (SEER) program registry of the National Cancer Institute comprising 158,621 invasive and 10,639 in situ cases of microscopically confirmed breast carcinomas registered for the years 1973-1987 have been analyzed. Relative frequencies, incidence rates, and 5-year relative survival rates were examined by selected variables of interest. Invasive and in situ breast carcinomas and sarcomas were analyzed separately. RESULTS: Infiltrating duct carcinoma was the largest group of female breast cancer, constituting 67.9% of the total with a 5-year relative survival of 79%. All other invasive carcinomas were compared with this group. Lobular carcinoma was the second largest group, only 6.3%, and a 5-year relative survival of 84%. Medullary carcinoma was the third most common with 2.8% and a 5-year relative survival of 82%. Other types included mucinous (colloid) adenocarcinoma, 2.2%, 5-year relative survival of 95%; comedocarcinoma, 1.4%, 5-year relative survival of 87%; Paget's disease (nipple and other breast), 1.1%, 5-year relative survival of 79%; papillary carcinoma, 0.9%, 5-year relative survival of 95%; tubular adenocarcinoma, 0.7%, 5-year relative survival of 96% and inflammatory carcinoma, 0.5%, 5-year relative survival of 18%. Carcinoma in situ was registered as intraductal, lobular, combined ductal and lobular, papillary, and carcinoma in situ, not otherwise specified. The relative survival for all forms of carcinomas in situ was approximately 100%. Sarcomas and malignant tumors not further classified are also considered. CONCLUSIONS: The various histologic types of breast cancer exhibit differences in regard to relative frequency, site pattern within the breast, and patient survival. The SEER program data base of breast cancer is the largest single population-based reference source for breast cancer in the United States. This program is a valuable resource for information on frequency, percentage, and incidence rates by histologic type as well as survival rates of patients with breast cancer. PMID- 8001001 TI - Female genital tract cancer. AB - BACKGROUND: Site-specific cancer frequencies and incidence rates are reported regularly by the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) program, but not by histologic type within site. This report reviews data for 160,977 histologically or cytologically confirmed invasive and in situ cancers of the female genital tract. METHODS: Data were supplied by the SEER program for histologically confirmed cases of uterine corpus, uterine cervix, ovary, vulva, vagina, fallopian tube, and placental cancers diagnosed between 1973 and 1987. Histologic types were reviewed for race, age at diagnosis, incidence, stage, and survival. RESULTS: There were 89,943 invasive and 71,034 in situ neoplasms. Squamous carcinoma was the most common invasive malignancy of the cervix (77.1%), vulva (74.4%), and vagina (70.8%). Adenocarcinoma was the most frequent malignancy in the uterine corpus (81.5%) and ovary (86.6%), with these percentages reaching 91.6% for corpus and 86.9% for ovary if adenosquamous carcinoma and adenocarcinoma with squamous metaplasia are included. Cervical carcinoma in situ accounted for 91.0% of all in situ cancers. In situ cancers made up 78.5% of all cervical cancers, 35.1% of vaginal cancers, and 50.4% of vulvar cancers. CONCLUSIONS: There are dominant histologic groups in each female genital tract site that are largely responsible for incidence and survival statistics. Within the groups, however, there are subtypes with differing features. Epidemiologic studies may provide more definite information by considering the effect of these subtypes in examining risk factors. PMID- 8001002 TI - Male genital cancers. AB - BACKGROUND: The estimated 165,000 cancers of the male genital system that will occur in the United States during 1993 represent one fourth of the expected 600,000 newly diagnosed cancers in American males for the year. METHODS: Data were collected by the Surveillance, Epidemiology, and End Results (SEER) program. This paper examines histologic data collected by the SEER program from 1973-1987 and focuses on incidence, stage at diagnosis, and survival for the dominant histologic types of cancer that occur in the four major topographic divisions of the male genital system: prostate gland, testis, penis, and scrotum. Some less common histologic types within each organ are also discussed. RESULTS: The incidence of male genital cancer has increased rapidly over the period of study. Cancers of the prostate, most of which are adenocarcinomas, represent more than 92% of all male genital cancers. Among adolescents and young men, germ cell cancers of the testis predominate, but decline rapidly in occurrence after 40 years of age. Blacks had higher incidence rates for prostate cancer than whites; however, the situation was reversed for testicular cancer. Survival increased dramatically for testicular cancer. Cancers of the penis and scrotum of any histologic type are uncommon in the United States. CONCLUSIONS: The increased incidence of prostate adenocarcinomas and testis germ cell tumors indicates the need for further etiologic studies as a basis for prevention efforts. PMID- 8001003 TI - Urinary system. AB - BACKGROUND: Although site-specific cancer frequencies and incidence rates for the United States are regularly reported by the National Cancer Institute's (NCI) Surveillance, Epidemiology, and End Results (SEER) program, they have not been reported by histologic type within a specific site. This report presents data for 76,303 cancers of the urinary tract by histologic type. METHODS: Cancer data were obtained from the SEER program. Urinary tract cancers were eligible if they were histologically confirmed, in situ or invasive, and diagnosed between 1973 and 1987. The urinary tract was divided into the following sites: kidney and renal pelvis, ureter, urinary bladder, urethra, and other urinary. Histologic types were evaluated by site, age, sex, race, incidence, and survival. RESULTS: Of the 76,303 cancers, 72.0% were transitional cell carcinomas and 22.0% were adenocarcinomas. Adenocarcinoma was the most common histologic type in the kidney and renal pelvis (also referred to as renal cell carcinoma), whereas transitional cell carcinoma was the most common histologic type in the remainder of the urinary tract. For the more common histologic types, age-adjusted incidence rates were always higher among males than females. CONCLUSIONS: Because adenocarcinomas represent most kidney and renal pelvis cancers and transitional cell carcinomas represent most urinary bladder cancers, these histologic types largely explain incidence and survival trends reported for these two common cancer sites. Future population-based cancer epidemiologic studies should try to focus more on specific histologic types within a cancer site to better clarify risk factors and incidence and survival trends for cancer. PMID- 8001004 TI - Brain, other central nervous system, and eye cancer. AB - BACKGROUND: The Surveillance, Epidemiology, and End Results (SEER) Program provides population-based data for the descriptive epidemiology of cancer incidence and survival rates by age, sex, race, and time period according to site and various histologic categories. METHODS: Relative frequencies, incidence rates, median age at diagnosis, and 5-year relative survival rates were analyzed by histologic type for microscopically confirmed primary malignant tumors of the brain, central nervous system (CNS) (except lymphomas), and eye, as well as olfactory neuroblastomas. RESULTS: Age-specific incidence rates for astrocytoma and glioblastoma, along with those for malignant meningioma, rose with increasing age up to 70-74 years, whereas rates for ependymoma and medulloblastoma (but not oligodendroglioma) showed a peak at age 0-4 years. Age-adjusted incidence rates for astrocytomas and glioblastomas were lower for blacks compared with whites, but there was little difference for rare types of brain/CNS cancers. Age-adjusted incidence rates increased slightly from 1973-1977 to 1983-1987 for astrocytoma, with little change for other histologic types. For cases diagnosed in 1983-1987, 5-year relative survival rates varied by histologic type and were low for astrocytoma, not otherwise specified (32%), and especially low for glioblastoma (4%); there was no evidence for improvement in survival rates for these two types from 1973-1977 to 1983-1987. Age-specific rates for eye melanoma rose with increasing age (especially for males), and age-adjusted rates were higher for whites than for blacks and declined from 1973-1977 to 1983-1987 in whites. Among cases diagnosed in 1983-1987, 5-year relative survival rates were high for melanoma of the eye (79%) and retinoblastoma (96%); only for retinoblastoma was there evidence of improvement in survival rates between 1973-1977 and 1983-1987. CONCLUSIONS: The SEER data are useful in examining the descriptive epidemiologic features, including time trends in incidence and survival rates, for primary cancers of the brain, CNS and eye. The lack of improvement in the low survival rates for some of these cancers emphasizes the remaining therapeutic challenges. PMID- 8001006 TI - Cancer of unknown primary site. AB - BACKGROUND: About 2% of more than 1 million cases of cancer diagnosed in residents of SEER areas for the 15-year period 1973-1987 were designated as being cancers of unknown primary site. METHODS: The 26,050 histologically diagnosed cancers of unknown primary site were studied. The small groups of other and ill defined sites within the respiratory and intrathoracic systems and other ill defined sites (546 total) were included in this total. RESULTS: Over the 15-year period, there has been a decrease in the number of these cancers for each race sex group. There has been very little change over time in the distribution by histologic type. The most frequent diagnosis was adenocarcinoma (around 55%), with approximately equal numbers of epidermoid carcinoma and carcinoma, not otherwise specified (about 14%). Changes in the frequency of mucinous, small cell, and large cell carcinoma have been observed. Carcinoid tumors of unknown primary site increased substantially. CONCLUSION: The decline in the numbers of cancers assigned to unknown primary site is to be welcomed. PMID- 8001005 TI - Endocrine gland cancer. AB - BACKGROUND: Incidence and prognosis of cancers of the endocrine glands vary greatly by histologic type. METHODS: Population-based data from SEER registries, 1973-1987, were analyzed. RESULTS: Thyroid cancer accounts for most (92%) of the cancers of the endocrine glands. The four major histologic types of thyroid cancer display distinct patterns, reflecting different biologic entities. Papillary carcinoma, the most common type, occurs more frequently in women than in men and in whites than in blacks and has an early onset. Follicular carcinoma, the second most common type, shows a steady increase in incidence with age and a female preponderance but no racial disparity. Medullary carcinoma, the rare differentiated thyroid tumor, has a female excess in whites only and a slow increase in incidence with age. Anaplastic carcinoma shows few racial or sex variations and reaches a substantial level only after age 50. The prognosis also varies greatly by histologic type. The overall 5-year relative survival rate is greater than 90% for papillary and follicular carcinomas, 82% for medullary carcinoma, and less than 10% for anaplastic carcinoma. Carcinomas of the suprarenal gland and thymus are rare, accounting for about 3% of endocrine cancers each. These tumors, unlike the differentiated thyroid cancer, show no female preponderance, have a higher incidence rate in blacks, and have a poorer survival rate. CONCLUSIONS: The marked predominance of papillary carcinoma and the continued increase in its relative frequency characterize the postgoiter era and an increased use of scintigraphy and fine needle aspiration. Underdiagnosis of small tumors may explain the observed lower incidence of papillary carcinoma in blacks. PMID- 8001007 TI - Hodgkin's disease. AB - BACKGROUND: Over three time periods, 1973-1977, 1978-1982, and 1983-1987, the Surveillance, Epidemiology, and End Results (SEER) program of the National Cancer Institute collected all cases of Hodgkin's disease in designated geographic regions representative of the United States as a whole. METHODS: The authors reviewed the data pertaining to 9418 microscopically confirmed cases of Hodgkin's disease and focused on trends that emerged over the time intervals of this study. RESULTS: Hodgkin's disease had a bimodal distribution of age-specific incidence rates with two peaks in the age groups of 15-34 years and older than 55 years. Since 1973, the incidence of Hodgkin's disease in the younger age group increased progressively as a result of a marked increase in the incidence of the nodular sclerosis subtype. From the period 1973-1977 to 1983-1987, the age-adjusted incidence rate of nodular sclerosis rose from 1.1 to 1.6 per 100,000. In 1983 1987, nodular sclerosis represented 57.7% of Hodgkin's disease and occurred most often in whites, with an equal sex ratio. In females, this increase in incidence over time was most dramatic in young adult women. The overall incidence of the mixed cellularity subtype, 23.4% of Hodgkin's disease, remained stable although the age-specific incidence rate increased progressively in black males older than age 40 years. The incidence of the lymphocytic predominance subtype, 6.0% of Hodgkin's disease, remained stable over time, with a slight increase in adults older than age 50 years. The lymphocytic depletion subtype, 3.8% of Hodgkin's disease, occurred predominantly in the elderly; its incidence decreased, most likely the result of changes in diagnostic criteria, with many cases being reclassified as non-Hodgkin's lymphoma (NHL). Similarly, unclassifiable cases of Hodgkin's disease designated as miscellaneous, 9.1% of Hodgkin's disease, decreased over time, probably the result of improved classification. Nevertheless, a subset of cases of Hodgkin's disease remained difficult to subclassify. The human immunodeficiency virus (HIV) epidemic appears to be associated with an increased incidence of Hodgkin's disease in San Francisco County in adult males age 30-49 years, a population known to have a high prevalence of HIV infection. CONCLUSION: The SEER data suggest that Hodgkin's disease is a heterogeneous entity composed of at least two different diseases- nodular sclerosis and mixed cellularity. Over the time course of this study, the incidence of nodular sclerosis increased dramatically, particularly in adolescents and young adults, whereas mixed cellularity remained stable. The incidence of Hodgkin's disease in the elderly decreased, most likely the result of our improved ability to diagnose both Hodgkin's disease and NHL and the realization that many cases of NHL had been misclassified as Hodgkin's disease. This decrease in Hodgkin's disease occurred predominantly in the lymphocytic depletion and miscellaneous groups. PMID- 8001008 TI - Non-Hodgkin's lymphoma. AB - BACKGROUND: Significant advances in the understanding of non-Hodgkin's lymphoma (NHL) have occurred in the past two decades, resulting in changes in terminology and classification practices, which may affect the analysis of the Surveillance, Epidemiology, and End Results (SEER) data. METHODS: The incidence rates for each subgroup of NHL in the Working Formulation were reviewed from the National Cancer Institute's SEER data during three time periods: 1973-1977, 1978-1982, and 1983 1987. RESULTS: NHL has significantly increased by 50% from 1973 to 1988. The most frequently occurring NHL is diffuse large cell lymphoma, constituting nearly 30% of all lymphomas. Increased incidence rates for large cell immunoblastic and small noncleaved cell NHL observed during the 1980s are attributable largely to the acquired immunodeficiency syndrome epidemic. Exposure to environmental agents such as herbicides and hair coloring dyes have recently been identified as factors that increase the risk of NHL, but the overall contribution of these factors remains to be identified. The increase in extranodal lymphomas is in part a consequence of the application of modern immunophenotypic and genotypic methods, which lead to the reclassification of pseudolymphomas as monoclonal B cell neoplasms. The apparent dramatic decline in the incidence of diffuse small cleaved NHL appears to be artifactual, as well, secondary to changes in classification of NHL. CONCLUSIONS: With the enhanced ability of pathologists to delineate new clinicopathologic entities by immunophenotypic and molecular biologic studies, future modifications to the collection of SEER data may be appropriate. Such an approach will address the limitations of the Working Formulation and lead to a more accurate data base for the evaluation of epidemiologic trends. PMID- 8001010 TI - Childhood cancer. AB - BACKGROUND: Cancers of individual organs generally are composed of various histologic types, each with its own frequency and demographic patterns. For childhood cancers in particular, a classification of cancers by histologic type is important for understanding the etiology and progression of the disease. METHODS: Data from the Surveillance, Epidemiology, and End Results (SEER) Program on 9308 microscopically confirmed malignant neoplasms in children younger than age 15, newly diagnosed during 1973-1987, were made available for analysis. Tumors were grouped histologically according to a classification previously utilized in an international volume of childhood cancer incidence. RESULTS: The most frequent histologic types were acute lymphocytic leukemia (23.6%), astrocytoma (9.6%), neuroblastoma (6.6%), and Wilms' tumor (6.4%). Acute lymphocytic leukemia accounted for 75% of childhood leukemia. The most common form of Hodgkin's disease was the nodular sclerosing subtype, which was diagnosed in 56% of all cases. Burkitt's and Burkitt-like disease accounted for approximately one third of non-Hodgkin's lymphoma, the sex ratio (male to female) being unusually high (5.7). Among the brain tumors, glioma was of interest because 198 cases (excluded from this analysis) were diagnosed without histologic confirmation--due, no doubt, to their inaccessibility for biopsy because they were located in the brain stem. The most common histologic type of soft tissue sarcoma was rhabdomyosarcoma, which accounted for 51% of the total, more than half of which were of the embryonal type. To the authors' knowledge, this report offers for the first time the relative frequencies of rare types of leukemias, such as megakaryoblastic leukemia, in childhood. This report also includes the frequencies of 21 rarer forms of soft tissue sarcoma. Five forms of childhood cancer had a 5-year relative survival rate of 85% or better. Of the cancers with the poorest outcome, three had relative survival rates of 46.5-49%; the relative survival rate of acute myelogenous leukemia was only 26.4%. The trends in survival over time for 21 types of childhood cancer also are included in this report. CONCLUSIONS: Further refinements in classification now are available through laboratory techniques utilizing molecular biology, immunology, and cytogenetics, which are of importance in etiologic studies, diagnosis, treatment, and prognosis. It would be important in the future for cancer registries to record the results of relevant laboratory tests for further analysis by subtype. PMID- 8001009 TI - Leukemias, myeloma, and other lymphoreticular neoplasms. AB - BACKGROUND: The purpose of this study was to assess the occurrence of various morphologic types of leukemia and myeloma within patient demographic groups and to correlate findings with data-reporting periods and other variables, such as 5 year relative survival. METHODS: Data from 31,850 cases of multiple subgroups of acute and chronic leukemia, 12,237 cases of myeloma, and 321 cases of "other" lymphoreticular neoplasms were collected by the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) program. The data were examined by age, sex, race, age-specific and age-adjusted incidence rate, and patient 5-year relative survival during three reporting periods: 1973-1977, 1978 1982, and 1983-1987. RESULTS: The age-adjusted incidence rate for all categories of leukemia combined has been constant, but there has been an increase in the relative frequency (percentage) of acute lymphoid leukemia (ALL) in the general population and a rising incidence rate of myeloid leukemia in the black population. The increase of ALL is offset by a decline of acute myeloid leukemias (AMLs) and acute leukemia, not otherwise specified. The age-adjusted rate of ALL in whites, 1.5 per 100,000 per year, is twice that of blacks, 0.8. The rates for each of the major categories of leukemia are considerably higher in males than in females. Five-year survival rates changed very little for leukemias over the 15 years of the study except for ALL, in which there was a marked improvement between the first (1973-1977) (39.1%) and second (1978-1982) (51.3%) reporting period. The SEER data confirm that multiple myeloma is predominantly a disease of late adulthood and occurs more frequently in blacks and males. The incidence rate of multiple myeloma has not changed during the 15 years surveyed. The 5-year relative survival rate has remained nearly constant for multiple myeloma. There is a marked difference in 5-year relative survival rates for patients with plasmacytoma of bone marrow (45.7%), multiple myeloma (25.9%), and plasma cell leukemia (13.0%). CONCLUSIONS: Shifts in the relative frequencies of leukemia types may have been affected by changes in classification criteria, changes in the use of histologic terms over time, and the expanded use of immunophenotyping and other technology to characterize acute leukemias. Incidence rates and 5-year relative survival rates for myeloma have remained stable. PMID- 8001011 TI - The histologic grading of cancer. AB - BACKGROUND: The histologic grade of a tumor provides prognostic information in addition to that provided by stage of disease. Poorly differentiated tumors are known to pursue a more aggressive course than their well differentiated counterparts. METHODS: The frequency of grading and the relationship of grade to outcome was investigated for 793,649 cases of cancer from 15 anatomic sites as recorded in the Surveillance, Epidemiology, and End Results Program. RESULTS: For all cancers, the frequency of grading increased from 1973 to 1987 and varied by anatomic site and histologic type. Survival decreased with advancing grade, and within each stage, grading separated cases into at least three distinct prognostic subgroups. For some cancers, regional stage cases assigned Grade 1 or 2 had higher survival rates than did localized stage cases assigned Grade 3 or 4. Therefore, grading allowed the identification of high and low risk subgroups within each stage grouping. CONCLUSIONS: The tumor grade was a strong prognostic indicator for cancers of the urinary bladder, endometrium, and prostate--sites most often graded by pathologists. The histologic grade was also an important determinant of outcome for cancers of the brain, soft tissue, and breast; however, only a small percentage of these tumors were graded. The results are important because no common criteria for grading were established among the many contributing pathologists. Therefore, observer variation did not alter the known relationship of histologic grade to outcome. This review demonstrates that the histologic grade is a strong predictor of outcome that refines the prognostic information provided by the stage of disease. PMID- 8001012 TI - Synthesis of a novel CMP-Neu5Ac analogue: CMP-[alpha-Neu5Ac-(2-->8)- Neu5Ac]. PMID- 8001014 TI - Structure of the polysaccharide Zanflo elaborated by Erwinia tahitica ATCC 217 11. PMID- 8001013 TI - Alpha-(2-->3)- and alpha-(2-->6)-sialyltransferase activities present in three variants of Ehrlich tumor cells: identification of the products derived from N acetyllactosamine and beta-D-Gal-(1-->3)-alpha-D-GalNAc-(1-->O)-Bn. AB - We compared several sialytransferase activities related to synthesis of O-linked and N-linked sialyglycoproteins in Ehrlich ascites tumor cells that grow normally in murine ascites, but are not adherent nor grow in tissue culture (na-EAT cells), with those in cells that were selected to grow in tissue culture and adhere to extracellular matrices (a-EAT cells). Crude Golgi preparations from both cell types contained predominantly beta-D-Gal-(1-->3)-D-GalNAc alpha-(2-->3) sialyltransferase activity. Sialylation of N-acetyllactosamine, lacto-N-tetraose, and benzyl alpha-D-GalNAc occurred at from 1 to 4% of that activity. Analysis, by ion-exchange HPLC at high pH, of sialylated N-acetyllactosamine showed that na EAT cells sialylated beta-D-Gal-(1-->4)-D-GlcNAc mostly by alpha-(2-->3) sialyltransferase, whereas beta-D-Gal-(1-->4)-D-GlcNAc alpha-(2-->6) sialyltransferase activity was prominent in a-EAT cells. In addition, preparations from na-EAT cells formed significant quantities of an unknown tritiated product from CMP-[9-3H]sialic acid, suggesting at least one other difference in enzyme levels between the cell types. a-EAT cells reestablished in murine ascites for 11 passages retained the sialyltransferase levels characteristic of a-EAT cells. When viable cells were labeled with D [3H]glucosamine, na-EAT cells formed larger amounts of sialic acid in O-linked glycoproteins than did a-EAT cells. PMID- 8001015 TI - Synthesis and spontaneous dimerization of the tri-O-benzyl derivative of "2-keto 1-C-methylene-D-glucopyranose" (2,6-anhydro-4,5,7-tri-O-benzyl-1-deoxy-D-arabino hept-1-en-3-ulose+ ++). PMID- 8001016 TI - Improved preparation of (+/-)-(1,3/2,4)-5-cyclohexene-1,2,3,4-tetrol [(+/-) conduritol-B] and its reaction with hydrobromic and hydrochloric acid; synthesis and characterisation of some (+/-)-1-deoxy-1-halo- and (+/-)- 1,4-dideoxy-1,4 dihalo-conduritols. PMID- 8001017 TI - Efficient preparation of allyl 2,3,6,2',3',6'-hexa-O-benzyl-beta-lactoside and its use as a glycosyl acceptor for chain extension at O-4'. PMID- 8001018 TI - Synthesis and investigation of the possible insulin-like activity of 1D-4-O- and 1D-6-O-(2-amino-2-deoxy-alpha-D-glucopyranosyl)-myo-inositol 1-phosphate and 1D-6 O-(2-amino-2-deoxy-alpha-D-glucopyranosyl)-myo-inositol 1,2-(cyclic phosphate). AB - The synthesis of the glycosyl-myo-inositol 1-phosphates 1 and 2 and of the glycosyl-myo-inositol 1,2-(cyclic phosphate) 3, starting from previously synthesized intermediates, is reported. Compound 3 was found to display proliferative effects on the early developing inner ear of chick embryo. PMID- 8001019 TI - Synthesis of a fucosylated and a non-fucosylated core structure of xylose containing carbohydrate chains from N-glycoproteins. AB - The synthesis is reported of methyl 2-acetamido-4-O-[2-acetamido-2-deoxy-O-(3,6 di-O-alpha-D- mannopyranosyl-2-O-beta-D-xylopyranosyl-beta-D-mannopyranosyl)-beta D- glucopyranosyl]-2-deoxy-beta-D-glucopyranoside (4) and methyl 2-acetamido-4-O [2-acetamido-2-deoxy-4-O- (3,6-di-O-alpha-D- mannopyranosyl-2-O-beta-D xylopyranosyl-beta-D-mannopyranosyl)-beta-D- glucopyranosyl]-2-deoxy-6- O-alpha-L fucopyranosyl-beta-D-glucopyranoside (5), which represent the invariant hexasaccharide core structure of the xylose-containing glycans of N-glycoproteins and its 6-O- fucosylated derivative. Ethyl 4-O-[3-O-allyl-4-O-benzoyl-6-O-tert butyldimethylsilyl-2-O- (2,3,4-tri-O-acetyl-beta-D-xylopyranosyl)- beta-D mannopyranosyl]-3,6-di-O-benzyl-2-deoxy-2-phthalimido-1- thio-beta-D glucopyranoside (9) was coupled with methyl 3,6-di-O-benzyl-2-deoxy-2-phthalimido beta-D- glucopyranoside (11). Desilylation of the resulting tetrasaccharide derivative, followed by condensation with 2,3,4,6- tetra-O-acetyl-alpha-D mannopyranosyl trichloroacetimidate (7), gave methyl 4-O-(4-O-[3-O-allyl-4- O benzoyl-6-O-(2,3,4,6-tetra-O-acetyl-alpha-D-mannopyranosyl)-2-O-(2,3,4 -tri-O- acetyl-beta-D-xylopyranosyl)- beta-D-mannopyranosyl]-3,6-di-O-benzyl-2-deoxy-2 phthalimido-beta-D- glucopyranosyl)- 3,6-di-O-benzyl-2-deoxy-2-phthalimido-beta-D glucopyranoside (14). Deallylation of 14, followed by condensation with 7 and deprotection, gave hexasaccharide 4. Ethyl 3,6-di-O- benzyl-2-deoxy-4-O- [4,6-di O-acetyl-3-O-allyl-2-O-(2,3,4-tri-O-acetyl-beta-D-xylopyranosyl) - beta-D mannopyranosyl]-2- phthalimido-1-thio-beta-D-glucopyranoside (17) was coupled with methyl 3-O- benzyl-2-deoxy-6-O- (4-methoxybenzyl)-2-phthalimido-beta-D glucopyranoside. Demethoxybenzylation of the tetrasaccharide derivative thus obtained, followed by fucosylation using ethyl 2,3,4-tri-O- benzyl-1-thio- beta-L fucopyranoside, gave methyl 3-O-benzyl-2-deoxy-4-O-[3,6-di-O-benzyl-2- deoxy-4-O [4,6- di-O-acetyl-3-O-allyl-2-O-(2,3,4-tri-O-acetyl-beta-D-xylopyranosyl)-beta -D mannopyranosyl]-2-phthalimido- beta-D-glucopyranosyl)-2-phthalimido-6-O-(2,3,4 tri-O-benzyl-alpha-L- fucopyranosyl)-beta-D-glucopyranoside (23). O-Deacetylation followed by tert-butyldimethylsilylation, benzoylation, and desilylation gave methyl 4-O-(4-O-[3-O-allyl-4-O-benzoyl-2-O-(2,3,4-tri-O-benzoyl-beta-D- xylopyranosyl)- beta-D-mannopyranosyl]-3,6-di-O-benzyl-2-deoxy-2-phthalimido-beta D-glucopyranosyl)-3- O-benzyl-2-deoxy-2-phthalimido-6-O-(2,3,4-tri-O-benzyl alpha-L-fucopy ran osyl)- beta-D-glucopyranoside (24). Mannosylation of 24 using 7, followed by deallylation, further mannosylation with 7, and deprotection, gave the heptasaccharide 5. PMID- 8001020 TI - Heteropolysaccharides of the lichen Evernia prunastri. AB - Extraction of Evernia prunastri with hot aqueous alkali solubilized heteropolysaccharide-containing material which was purified via Fehling precipitation. Further workup of this polysaccharide with Cetavlon gave two fractions having related but different structures. Each structure consisted of a 1-->6-linked alpha-D-Man p main chain partially monosubstituted at O-2 with side chains of alpha-D-Gal p and partially disubstituted at O-2 and O-4 with alpha-D Gal p and beta-D-Gal p, respectively. The fractions differed in that one contained much more uronic acid than the other, with corresponding predominance of side chains containing alpha-D-Glc pA-(1-->3)-D-Glc p, alpha-D-Gal p-(1-->2)-D Glc p, and beta-D-Gal f units. PMID- 8001021 TI - Isolation and structural characterization of endo-rhamnogalacturonase-generated fragments of the backbone of rhamnogalacturonan I. AB - A combination of commercially available preparations of Aspergillus niger beta-D galactosidase, endo-alpha-L-arabinanase, alpha-L-arabinosidase, and endo-beta-D galactanase has been used to generate oligoglycosyl fragments of the backbone of rhamnogalacturonan I (RG-I) that had been isolated from the walls of suspension cultured sycamore cells. The backbone-cleaving enzyme, which is present in the beta-D-galactosidase preparation, only fragments the RG-I backbone when many of the neutral oligoglycosyl side chains have been removed by the other exo- and endo- glycanases. The oligosaccharides released from the backbone were separated from the partially fragmented RG-I and then purified, as their oligoglycosyl aldonic acids, by HPAEC-PAD. Those backbone fragments with degrees of polymerization (dp's) between 2 and 11 were characterized using one- and two dimensional 1H NMR spectroscopy, electrospray mass spectrometry, and glycosyl residue and glycosyl-linkage composition analyses. Two series of oligoglycosyl fragments were identified. The quantitatively predominant series has the structure alpha-D-GalpA-(1 --> 2)- alpha-L-Rhap-[ --> 4)-alpha-D-GalpA-(1 --> 2) alpha-L-Rhap-(1 --> ]n-4-D-GalpA, and the quantitatively minor series has the structure alpha-L-Rhap-[ --> 4)-alpha-D-GalpA-(1 --> 2)-alpha-L-Rhap-(1 --> ]n-4 D- GalpA (n = 1-5). Thus, the enzyme preparations contain an alpha-L-rhamnosidase in addition to the endo- rhamnogalacturonase. The products of the endo rhamnogalacturonase provide additional evidence that the backbone of RG-I is composed of the diglycosyl repeating unit: --> 4)-alpha-D-GalpA-(1 --> 2)-alpha-L Rhap- (1 -->. The endo-rhamnogalacturonase from the A. niger beta-D-galactosidase preparation and the endo- rhamnogalacturonase secreted by Aspergillus aculeatus [H.A. Schols et al. Carbohydr. Res., 206 (1990) 117-129] have the same substrate specificities and generate similar oligoglycosyl fragments. PMID- 8001022 TI - Patho- and immunobiology of malignant mesothelioma: characterisation of tumour infiltrating leucocytes and cytokine production in a murine model. AB - Malignant mesothelioma (MM) is an aggressive, uniformly fatal serosal tumour, usually associated with asbestos exposure, for which there currently is no effective treatment. In order to gain insight into the mechanism(s) whereby MM might escape immune surveillance, a murine model for MM was used (a) to characterise the tumour-infiltrating lymphocytes (TIL) and macrophages (TIM) phenotypically, (b) to examine systemic immune recognition of MM, and (c) to examine the possible influence of tumour-derived cytokines on systemic and local pathobiological manifestations of MM. A profound down-regulation of lymphocyte surface markers, known to be involved in T cell activation, was found in TIL. Likewise, although TIM were present in large numbers, their expression of MHC class II antigen and integrins was weak or absent, suggestive of altered functional activity. Significant amounts of cytokines, in particular transforming growth factor beta, interleukin-6 (IL-6), IL-1 and tumour necrosis factor were produced during the course of MM tumour development-directly by the MM cells and/or indirectly in response to tumour growth. These factors may contribute both to derangement of antitumour effector mechanisms and to the clinical and pathological manifestations of the disease. PMID- 8001024 TI - Characterization of murine and humanized anti-CD33, gelonin immunotoxins reactive against myeloid leukemias. AB - M195 antibodies recognize CD33, an antigen present on acute myeloid leukemia blasts as well as some myeloid progenitor cells, but not on the ultimate hematopoietic progenitor stem cell. Immunotoxins (IT) reactive with human myeloid leukemias were constructed by conjugating gelonin, a single-chain ribosome inactivating protein, to murine and genetically engineered, humanized M195 antibodies via an N-succinimidyl-3-(2-pyridyl-dithio)-propionate linkage. No losses of gelonin cytotoxic activity or M195 binding activity were observed after conjugation of up to two toxin molecules per antibody. Toxin conjugates displayed specific, potent toxicity for CD33+ cells. The murine and humanized IT were not toxic to CD33- cells and were 600 and 4500 times more potent, respectively, than free gelonin in inhibiting CD33+ HL60 cells. Treatment of HL60 cells with 1 micrograms/ml HuM195-gelonin resulted in more than 1000 times lower colony formation; normal bone marrow mononuclear cell colony-forming units treated with HuM195-IT were reduced by a factor of 10. HL60 leukemia cells could be effectively purged from an excess of normal bone marrow cells. Exposure of target cells to IT for as little as 30 min was as effective as continuous exposure of IT for up to 6 days. However, measures of the efficacy of the immunotoxin were directly related to the length of time of observation after IT exposure and were inversely related to cell concentration. M195-gelonin immunoconjugates are potential candidates for therapeutic use in in vivo or ex vivo bone marrow purging for myeloid leukemias. PMID- 8001025 TI - Differences in biodistribution of the anti-(carcinoembryonic antigen) murine monoclonal antibody CE-25, its F(ab')2 fragment and its intact mainly human chimeric form CE 4-8-13. Dependence on tumour size and amount of antibody injected. AB - The effect of the size of the tumour and the amount of antibody injected on the biodistribution of a family of radioiodinated antibodies was studied. The intact mouse anti-(carcinoembryonic antigen) (anti-CEA) monoclonal antibody CE-25, its F(ab')2 fragment and the intact human-mouse chimeric from CE 4-8-13 were evaluated in a model system using the human CEA-producing colon xenograft T 380 grown in nude mice. The relative retention (the percentage of the injected dose per gram of tissue), of mouse mAb and F(ab')2 in tumour and most normal tissues 1 day after injection was independent of the antibody dose; after 4 days the mAb values increased with increasing antibody dose. The relative retention of chimeric mAb increased with increasing antibody dose 1 day after injection and also slightly after 4 days. The relative retention in tumour tissue was lower in bigger xenografts for all antibodies. The relative retention of mouse mAb in small tumours increased from day 1 to day 4; for chimeric mAb this value decreased. In normal tissues the relative retention of mouse mAb decreased from day 1 to day 4, but the relative retention of chimeric mAb in normal tissue dropped rapidly and changed little afterwards. Thus the biokinetics of antibodies is "species"-dependent: foreign, mainly human, chimeric antibody clears faster from normal mouse tissue than mouse antibody and reaches lower concentrations. PMID- 8001023 TI - Effect of murine interferon alpha/beta on tumour-induced suppressor function. AB - T-lymphocyte-mediated immunosuppression has been described in several animal models and in man. In animal models. T-cell-mediated immunosuppression can hasten the development of cancers, permit the growth of tumors in immunocompetent hosts, and inhibit otherwise effective antitumor immunotherapy. Cyclophosphamide can abrogate the T-cell-mediated immunosuppression. However, inappropriately administered cyclophosphamide can adversely affect antitumor immunity. On the basis of data showing that interferon alpha/beta (IFN alpha/beta) and IFN beta selectively abrogate the T-cell-mediated dinitrofluorobenzene-specific suppressor function, we investigated the efficacy of purified murine IFN alpha/beta in manipulating tumor-induced T-cell-mediated immunosuppression in the well characterized P815 mastocytoma model. In this model, generation of cytotoxicity in vitro and its inhibition by T cells correlates with antitumor immunity in vivo. We report that IFN alpha/beta selectively diminishes the generation of tumor-induced suppressor activity. PMID- 8001027 TI - Clinical pharmacology and tissue disposition studies of 131I-labeled anticolorectal carcinoma human monoclonal antibody LiCO 16.88. AB - Antibody LiCO 16.88 is a human IgM recognizing a 30- to 45-kDa intracytoplasmic antigen present in human adenocarcinoma cells. An 8-mg sample of antibody labeled with 5 mCi 131I was co-administered i.v. with 120 mg (three patients), 240 mg (three patients) or 480 mg (four patients) unlabeled antibody as a 4-h infusion. The plasma half-life was 24 +/- 1.2 h and the immediate apparent volume of distribution was 5.2 +/- 0.2 l at the 28-mg dose level. The plasma half-lives and the cumulative urinary excretion of radiolabel did not seem to vary significantly with increasing doses of unlabeled antibody. However, both the volume of distribution and the clearance rate from plasma increased significantly with increasing antibody dose. Uptake of antibody into tumor tissues obtained during laparotomy 8-9 days after administration varied between 0.00002% ID/g and 0.00127% ID/g. In five of seven patients, the tumor content of antibody was higher than that in adjacent normal tissue. Tumor-to-normal tissue ratios ranged from 0.8 to 10 (mean = 3.8 +/- 1.0). In general, the higher radioactivity(cpm)/g tumor was confirmed by both immunoperoxidase and autoradiography. Antibody 16.88 localizes in tumors after administration and may be considered for use in radioimmunotherapy trials. PMID- 8001026 TI - In vivo infiltration of mononuclear cells in squamous cell carcinoma of the head and neck correlates with the ability to expand tumour-infiltrating T cells in vitro and with the expression of MHC class I antigens on tumour cells. AB - A series of 18 head and neck squamous cell carcinoma biopsies, 6 primary and 12 recurrent, were investigated for tumour-infiltrating mononuclear cells with monoclonal or polyclonal antibodies. Our results suggest that the number of T cells at the tumour edge in vivo correlates well with their ability to expand in vitro in the presence of high-dose interleukin-2 (2000 U/ml). High MHC class I antigen expression on tumour cells was found to be positively correlated with p53 overexpression, suggesting that p53-derived peptides, wild-type or mutated ones, presented by MHC class I antigens, are potential targets for MHC-restricted cytotoxic T cells in head and neck squamous cell carcinomas. However, lack of correlation between peritumoural T cell infiltration in vivo and T cell expansion in vitro, on the one hand, and p53 overexpression on tumour cells, on the other hand, suggests absence of p53-peptide-specific T cells in the patients. Eight out of ten expanded tumour-infiltrating lymphocyte (TIL) cultures showed T-cell mediated cytotoxicity. "Promiscuous" cytotoxic T cell activity against the natural-killer-cell-sensitive K562 target cell line was observed in three out of ten TIL expansion cultures. PMID- 8001028 TI - Induction of TH1- and TH2-associated cytokine mRNA in mouse bladder following intravesical growth of the murine bladder tumor MB49 and BCG immunotherapy. AB - Productive immunity to murine and human parasites is associated with the development of a type I T cell response (interferon-gamma-producing) while type II responses (interleukin-4-producing) suppress the development of delayed-type hypersensitivity (DTH) and the elimination of the parasite. To determine if a similar regulatory pathway might exist in tumor systems and may be effected by immunotherapeutic manipulation, we have studied the localized cytokine response to the murine bladder tumor MB49 growing intravesically in syngeneic mice. Intravesical growth of MB49 results in the host-derived expression of mRNA for both interleukin-4 (IL-4) (TH2) and interferon gamma (IFN gamma) (TH1), as well as tumor necrosis factor alpha (TNF alpha) expression of indeterminate origin. Intravesical instillation of bacillus Calmette-Guerin (BCG), highly effective in eliminating bladder tumors clinically and in experimental systems, results in IFN gamma and TNF alpha mRNa production in the bladder wall, but no IL-4. Following BCG treatment of intravesical MB49, the number bladders expressing IL-4 mRNA decreases, while IFN gamma and TNF alpha expression remains constant. These results are consistent with the mechanism of action of BCG involving the generation of an enhanced TH1 immune milieu in the bladder wall, which may contribute to the generation of productive tumor-specific immunity. PMID- 8001029 TI - Proliferation of hematopoietic cell lines induced by a soluble factor derived from human squamous cell carcinomas of the head and neck. AB - The supernatant of a cell line of squamous cell carcinoma of the head and neck (SCCHN), PCI-50, was previously shown to induce activation, promote proliferation and increase antitumor cytotoxicity of freshly purified human natural killer (NK) cells and CD4+ T lymphocytes [Arch Otolaryngol Head Neck Surg (1994) in press]. This supernatant was found also to promote the growth of a variety of hematopoietic cell lines, including Jurkat, THP-1, K562, NK-92 or Epstein-Barr virus-transformed B cell lines. The Jurkat cell line was selected as a reporter cell in an 18-h proliferation assay established to measure the growth-promoting activity of PCI-50 supernatant. The presence of soluble tumor-derived factors able to induce proliferation of Jurkat cells was demonstrated in the supernatant produced by several other SCCHN cell lines but not in that produced by a gastric cancer cell line (HR) or renal cell carcinoma line (5117G8). The growth-promoting PCI-50 supernatant was shown to contain 28 +/- 0.5 pg/ml interleukin-6 (IL-6) in vitro but was negative for interferon gamma, IL-1, IL-2, IL-4, tumor necrosis factor alpha, granulocyte/macrophage-colony-stimulating factor and IL-12. The addition of any of these recombinant cytokines to Jurkat cell cultures did not significantly promote growth, while PCI-50 supernatant was consistently growth stimulatory. This supernatant neither enhanced intracellular Ca2+ concentration in Jurkat cells nor induced up-regulation of activation antigens on the cell surface, although it supported growth of Jurkat cells in the absence of IL-2. The growth-promoting activity in the PCI-50 supernatant was acid-labile at pH 2 for 4 h, heat-resistant at 96 degrees C for 1 h and sensitive to treatments with trypsin and pepsin. Preincubation of the PCI-50 producer cells with tunicamycin or cyclohexamide reduced the level of growth-promoting activity in the supernatant. A partial purification of this activity was achieved using Amicon filtration, chromatography on concanavalin-A-Sepharose and then a hydroxyapatite column and high-pressure liquid chromatography gel filtration. The partially purified glycoprotein had a molecular mass of 50-70 kDa, as determined by gel filtration. PMID- 8001031 TI - Mechanisms of beta adrenoceptor desensitisation in the failing human heart. PMID- 8001032 TI - Does ischaemic preconditioning occur in the human heart? PMID- 8001030 TI - Histamine in immunotherapy of advanced melanoma: a pilot study. AB - Sixteen patients with advanced metastatic malignant melanoma were treated with a high-dose infusion of interleukin-2 (IL-2; 18 x 10(6) IU/m-2 day-1) together with daily subcutaneous (s.c.) injections of interferon alpha (IFN alpha; 3 x 10(6) U/m-2 day-1) in 5-day cycles. Nine of these patients were given histamine (1 mg s.c.) twice daily during treatment with IL-2 and IFN alpha. In the seven patients who did not receive histamine, one partial response (that is a reduction of more than 50% in the total tumour burden) was observed in a patient with skin and lymph node melanoma. In the eight histamine-treated patients evaluable for response, four partial responses were observed. Two other patients showed regression at one site of metastasis but tumours remained unchanged at other sites. Two histamine-treated patients showed complete resolution of extensive liver metastasis. Sites of response in histamine-treated patients also included the subcutis, lymph nodes, skeleton, spleen and muscle. Lung melanoma did not respond to histamine/IL-2/IFN alpha. Three patients with lung tumours responded with significant (more than 50%) reduction of the volume of soft-tissue tumours, suggesting that the response to histamine may be organotropic. Survival was significantly prolonged in patients receiving histamine. Our data suggest that treatment with histamine may improve the antitumour efficacy of immunotherapy in metastatic melanoma. PMID- 8001033 TI - Developments in non-radioactive microsphere techniques for blood flow measurement. AB - Considerable progress is being made in the development of non-radioactive microsphere methods. Validation studies of the three commercially available non radioactive microspheres are promising. In most experimental conditions the use of non-radioactive microspheres saves money. Avoiding the use of radioactivity facilitates the use of microspheres in chronic animal experiments and when blood flow and chemical measurements are performed in the same sample. Moreover, using histological techniques, distributions of coloured or fluorescent microspheres in subunits of organs could be quantified, opening new scientific possibilities. Currently, the fluorescent microsphere technique seems to be the most promising non-radioactive microsphere method. Due to the high sensitivity and good spectral separation, the number of microspheres injected can be as small as that used, for radioactive microspheres, at least six labels can be used, and the relatively large volume in which fluorescence is measured (approximately 1-3 ml) enables the use of time saving microsphere isolation techniques. Development of these methods and further automation of the quantification process (using either automised spectrometry or FACS analysis) will considerably increase interest in the non radioactive microsphere techniques. To accelerate these developments, investigators are encouraged to share their experiences. PMID- 8001035 TI - Effect of duration of depolarisation on contraction of normal and hypertrophied feline ventricular myocytes. AB - OBJECTIVE: The aim was to test the hypothesis that the prolongation of action potential duration in hypertrophied feline myocytes causes the contractions to be of long duration. METHODS: Left ventricular hypertrophy was induced by slow progressive pressure overload after banding the ascending aorta of young cats. Single myocytes were enzymatically dissociated for whole cell patch clamp studies. Cell shortenings were induced by stimulated action potentials (in current clamp mode) and by step depolarisations using voltage clamp to control the duration of depolarisation. RESULTS: Action potential duration measured at 50% repolarisation (0.5 Hz) was significantly longer in hypertrophied myocytes, at 688(SEM 43) ms, n = 25, v 396(17) ms, n = 22, in control myocytes (p < 0.01). The associated contractions in hypertrophied myocytes had significantly longer durations measured at 50% relengthening [hypertrophied myocytes 609(54) ms, control myocytes 406(13) ms]. The absolute magnitude of shortening normalised to percent diastolic cell length was also significantly reduced in hypertrophied myocytes [7.8(0.8)% diastolic cell length] compared to control myocytes [12.2(0.6)% diastolic cell length] and the duration of contraction time to 50% relengthening was prolonged [406(13) ms v 609(54) ms]. When the duration of depolarisation was controlled with voltage clamp techniques, steady state contractions at +10 mV increased in magnitude in both control and hypertrophied myocytes as the duration of depolarization was lengthened. At all durations tested (100-1000 ms), contractions were significantly longer in duration in hypertrophied myocytes. Changing the duration of depolarisation had no significant effect on the duration of contraction in control myocytes. In hypertrophied myocytes, however, prolongation of depolarisation (500-1000 ms) significantly prolonged the contraction. Steady state contractions initiated from -70 mV (sodium current activated) were larger in both control and hypertrophied myocytes than contractions elicited from -40 mV (sodium current inactivated), and the effect of depolarisation duration on contractile duration was the same. CONCLUSIONS: Changes in sarcolemmal properties which produce a lengthening of the action potential duration in hypertrophy are not primarily responsible for the prolongation of contractile duration. However, there is a portion of contraction which becomes sensitive to the duration of depolarisation in hypertrophied myocytes. PMID- 8001034 TI - Alteration of lysophosphatidylcholine content in low density lipoprotein after oxidative modification: relationship to endothelium dependent relaxation. AB - OBJECTIVE: The aim was to examine the formation of lipid peroxidation products and the alteration in phospholipid content in low density lipoprotein (LDL) after oxidative modification by CuSO4, and subsequently, to determine the ability of the modified LDL to impair endothelium dependent relaxation in rat aortic rings. METHODS: Blood samples were obtained from normal human volunteers. LDL was prepared by sequential ultracentrifugation and it was oxidatively modified in the presence of 5 microM CuSO4. Lipid peroxidation products (thiobarbituric acid reactive substances, TBARS), and alterations in electrophoretic mobility and phospholipid content were determined in normal (native) and oxidised LDL. Endothelium dependent relaxation was produced by acetylcholine (10(-8)-10(-5) M) in phenylephrine precontracted rat aortic rings. RESULTS: LDL incubated for 24 h with 5 microM CuSO4 at 20 degrees C and 37 degrees C with constant agitation displayed higher amounts of TBARS than the respective native LDL. While the amounts of TBARS in LDL modified at 20 degrees C and 37 degrees C were similar, the former condition resulted in statistically smaller changes of phospholipid contents. LDL with higher lysophosphatidylcholine content showed greater impairment of endothelium dependent relaxation in rat aortic rings than LDL with lower lysophosphatidylcholine content. CONCLUSIONS: The raised lysophosphatidylcholine level in oxidatively modified LDL was related to the ability of the LDL to impair endothelium dependent relaxation. However, lipid peroxidation products assessed by TBARS did not relate to the phospholipid changes in LDL and therefore cannot be used to predict the vascular effects of LDL after oxidative modification. PMID- 8001036 TI - Human endocardial innervation and its relationship to the endothelium: an immunohistochemical, histochemical, and quantitative study. AB - OBJECTIVE: The endocardium contains an extensive neural plexus, the composition and function of which are unclear. The aim of this study was to characterise the innervation of the endocardium in terms of the relative density and distribution of its autonomic and sensory nerve subpopulations and to assess the relationship between these nerves and endocardial endothelial cells. METHODS: Immunohistochemical, histochemical, confocal, and quantitative image processing techniques were applied to whole mount preparations of human postmortem endocardium obtained within 24 h of death. RESULTS: The overall distribution of nerve fibres and fascicles was demonstrated using antisera to the general neural marker protein gene product 9.5 (PGP 9.5). Nerves displaying acetylcholinesterase activity represented the main nerve subpopulation, occupying 9-18% of the quantified field area. Neuropeptide Y immunoreactive nerves formed the most numerous peptide containing nerve subpopulation identified, occupying 5-19% and 2 7% of the field area in the ventricle and atrial endocardium respectively and having similar distribution patterns to tyrosine hydroxylase immunoreactive nerves. Nerves showing immunoreactivity for somatostatin, vasoactive intestinal polypeptide, and substance P were detected at a lower density, occurred more frequently in the ventricular than atrial endocardium, and showed a similar distribution in the right and left sides of the heart. Combined peptide immunofluorescence and acetylcholinesterase staining, of the same preparation, indicated that putative sympathetic and sensory nerve subpopulations could be distinguished from presumed parasympathetic, acetylcholinesterase positive, nerves. The relationship between immunostained nerves and endothelial cells was assessed using confocal microscopy. Varicose nerve fibres were detected within 0.2 micron of overlying endothelial cells in the right ventricle and between 0.4 0.6 micron in the left ventricle. CONCLUSIONS: The heterogeneous population of nerve fibres demonstrated in the human endocardium may influence the known interaction between endocardial endothelial cells and the myocardium. PMID- 8001037 TI - Effects of 21-aminosteroids in neonatal rat cardiac myocyte cell cultures exposed to free radicals. AB - OBJECTIVE: The aim was to test a group of 21-aminosteroids, U74006F, U75412E, and U74500E, known as lazaroids, for their ability to prevent alterations in neonatal rat cardiac myocytes exposed to solutions containing a xanthine oxidase mediated free radical generating system. METHODS: Myocytes were either left untreated (non treated cultures) or pretreated for 15 min with the drug vehicle or one of the lazaroids. Myocytes were either examined as non-exposed control cultures or exposed to the free radical generating system for 60 min. Measurement of [3H]arachidonate label in a lipid extract of the culture medium and release of lactate dehydrogenase (LDH) into the medium were analysed. RESULTS: Myocytes not treated with lazaroids and vehicle treated myocytes exposed to free radicals showed a significant release of [3H]arachidonate and lactate dehydrogenase (LDH). At a dose 1 x 10(-5) M, all lazaroid treated myocytes showed significantly lower release of [3H]arachidonate measured in the total lipid extract compared to the non-treated or vehicle treated cultures. Release of [3H]arachidonate was significantly lower for the myocytes treated with U74006F and U74500E at 1 x 10( 6) M concentration. Only the U74006F treated myocytes showed protection at 1 x 10(7) M. LDH release was significantly attenuated at a dose of 1 x 10(-5) M for the U75412E treated myocytes and at 1 x 10(-5) and 1 x 10(-6) M for the U74500E treated myocytes compared to the myocytes not pretreated with a lazaroid and exposed to free radicals. CONCLUSIONS: Lazaroids provide protection against the release of [3H]arachidonate and LDH from myocardial cells exposed to free radical mediated injury. U74006F appeared to have the higher efficacy, at equal molar concentrations, in protecting against the release of [3H]arachidonate, whereas U74500E was observed to have the higher potency in inhibiting LDH release. PMID- 8001038 TI - Modulation of sodium current by lactate in guinea pig ventricular myocytes. AB - OBJECTIVE: The aim was to elucidate whether or not lactate modifies the fast sodium current (INa) in cardiac cells. METHODS: A tight seal whole cell clamp technique was used to record the action potentials and INa in single ventricular cells from the guinea pig heart. RESULTS: In voltage clamp experiments, superfusion with 20 mM lactate shifted both the normalised conductance (gNa) voltage relationship and the channel availability curve toward hyperpolarisation by approximately 4 mV, but did not affect the maximum conductance (gNa,max). In the test solution containing only CaCl2 as the main divalent component, 20 mM lactate reduced the ionised calcium concentration from 1.02 to 0.84 mM. When the calcium concentration was kept constant by the addition of CaCl2 into the lactate containing solution the lactate effect was nullified. However, a change in the calcium concentration from 1.0 to 0.84 mM without lactate induced a 4 mV negative shift of the channel availability curve. Current clamp experiments in Tyrode solution showed that 20 mM lactate shifted the threshold for the action potential upstroke by 2.5-3 mV, in accordance with the voltage clamp experiments. CONCLUSIONS: Lactate modifies INa of ventricular myocytes by shifting its kinetics toward hyperpolarisation. This shift seems to be caused exclusively by a decrease in the ionised divalent cation concentrations and a resultant change in the negative surface charge of the sarcolemma. PMID- 8001039 TI - Synergistic action of vasodilators that increase cGMP and cAMP in the hamster cremaster microcirculation. AB - OBJECTIVE: Compounds such as endothelium derived nitric oxide (NO) and prostacyclin (prostaglandin I2) which increase cGMP and cAMP inhibit platelet activation in a synergistic manner. The aim of this study was to examine whether these compounds also interact synergistically in the control of smooth muscle tone. METHODS: Vascular diameters in the cremaster of 49 anaesthetised hamsters (465 arterioles) were studied during superfusion with compounds raising cAMP (isoprenaline and prostacyclin) and cGMP (sodium nitroprusside) alone or in combination. RESULTS: (1) The isoprenaline induced maximum dilator response was significantly attenuated, from 86.1(SEM 0.7)% to 37.1(0.2)%, after inhibition of NO-synthase with NG-nitro-L-arginine (L-NNA, 30 microM). Superfusion with sodium nitroprusside (30 nM, dilatation alone: 6.7%), which was used to substitute for endothelium derived NO, restored the attenuated isoprenaline response. The combined effects of isoprenaline and sodium nitroprusside were supra-additive. Virtually identical results were obtained when prostacyclin, another cAMP raising compound, was used instead of isoprenaline. The K+ channel opener cromakalim (100 nM) which acts cGMP independently was without effect on the prostacyclin induced dilator response. (2) The sodium nitroprusside induced maximum dilator response was attenuated from 80.9(0.25)% to 70.1(0.4)%, after indomethacin (3 microM) and restored by simultaneous application of prostacyclin (1 nM, dilatation alone: 1.4%) but not of cromakalim. Again, the combined effects were supra-additive, suggesting a synergistic action of these compounds. (3) Although indomethacin or L-NNA alone decreased the resting diameter by approximately 9.5%, the simultaneous application of both inhibitors failed to decrease the resting diameter further (10.0%, p = 0.97). CONCLUSIONS: Vasodilators increasing cGMP and cAMP act synergistically in vivo. Continuous release of NO and prostaglandins by the endothelium may therefore not only modulate the efficacy of such cyclic nucleotide increasing vasodilators but also interact synergistically in controlling basal vascular tone. PMID- 8001040 TI - Selective changes in natriuretic peptide and early response gene expression in isolated rat atria following stimulation by stretch or endothelin-1. AB - OBJECTIVE: Important physiological and pathophysiological conditions are associated with changes in secretion and synthesis of atrial natriuretic factor (ANF) and brain natriuretic peptide (BNP). The aim of this study was to examine the effects of mechanical stretch and endothelin-1 on ANF and BNP secretion and gene expression in isolated adult rat atria, as paradigms for mechanical and endocrine stimulation of atrial tissue. The expression of the early response genes c-fos, c-jun, Egr-1, and c-myc was also studied, since their protein products may be involved in controlling natriuretic peptide gene expression. METHODS: Isolated rat atria were stimulated by stretch (5 g) or endothelin-1 (10( 7) M) for 30 min, 2 h, or 4 h. ANF and BNP secretion was measured by radioimmunoassay, and relative mRNA levels were determined by northern blotting. RESULTS: Atrial stretch resulted in an immediate 1.8-fold increase in ANF release, which returned to basal levels after 160 min. Endothelin-1 caused a gradual increase in ANF release, up to 2.3 times basal levels, and thereafter returned towards basal levels. BNP secretion was increased threefold by endothelin-1, and remained significantly raised for 90 min. BNP mRNA levels were transiently increased by 33% after 2 h of endothelin-1 stimulation. Stretch increased c-fos mRNA levels (+55%) and Egr-1 mRNA levels (+70%) after 2 h, and increased c-myc mRNA levels (+69%) after 4 h. Endothelin-1 increased Egr-1 mRNA levels up to +767% after 4 h. CONCLUSIONS: Endothelin-1 stimulates BNP secretion from rat atria; this is followed by an increase in BNP mRNA levels. Conversely, acute secretion of ANF by stretch or endothelin-1 is not accompanied by changes in ANF mRNA levels. Atrial stretch results in changes in the expression of the early response genes c-fos, Egr-1, and c-myc, while endothelin-1 stimulates Egr-1 expression. The specific changes in natriuretic peptide and early response gene expression reveal distinct mechanisms of modulation of atrial gene expression by mechanical and endocrine stimuli. PMID- 8001041 TI - The novel calcium antagonist Ro 40-5967 limits myocardial infarct size in the dog. AB - OBJECTIVE: The aim was to compare the infarct limiting effect of Ro 40-5967 (Ro40), a new calcium antagonist with little negative inotropic activity, with that of verapamil and with ischaemic preconditioning, a potent endogenous cardioprotective mechanism. METHODS: Dogs (n = 53) of either sex were subjected to 60 min of coronary occlusion followed by 3 h of reperfusion. Drug treated dogs received either verapamil (1.0 mg.kg-1) or Ro40 (3.0 mg.kg-1) intravenously for 100 min starting 15 min prior to the occlusion. Control dogs received a saline infusion. Ischaemic preconditioning consisted of four 5 min cycles of ischaemia alternating with four 5 min cycles of reperfusion. After 3 h of reflow, hearts were excised and infarct size was measured using tripheyltetrazolium chloride macrochemistry and expressed as percent of the ischaemic area at risk (AAR). To control for variation in infarct size due to variation in collateral blood flow, infarct size among groups was compared using ANCOVA, in which infarct size and collateral blood flow, measured at 30 min of occlusion, were dependent and independent variables, respectively. RESULTS: Transmural collateral blood flow and AAR were not significantly different between any of the groups. Mean infarct size (adjusted by ANCOVA for slight differences in collateral blood flow among groups) in control dogs (n = 13) was 25.9(SEM 3.2)% of the AAR. Both verapamil (n = 11) and Ro40 (n = 9) limited infarct size [14.2(3.2)% AAR and 16.7(2.9)% AAR, respectively; both p < 0.05]. Preconditioning (n = 17) also significantly limited infarct size [8.1(1.8)%; p < 0.01]. CONCLUSIONS: The new calcium antagonist, Ro 40-5967, was as effective as verapamil in limiting infarct size after 60 min of regional ischaemia followed by 3 h of reperfusion, although neither calcium antagonist was as effective as ischaemic preconditioning. PMID- 8001042 TI - Captopril treatment does not restore either the renal or the ANF release response during volume expansion in moderate to severe high output heart failure. AB - OBJECTIVE: Atrial natriuretic factor (ANF) release and the renal response to moderate volume expansion have been shown to be conserved in rats with a mild to moderate degree of high output heart failure (aortocaval shunt). The aim of this study was to investigate whether these variables are also conserved in animals with moderate to severe heart failure induced by an aortocaval shunt. The effect of angiotensin converting enzyme (ACE) inhibition by captopril on these responses was also investigated. METHODS: An aortocaval shunt was developed in Sprague Dawley rats weighing 180-200 g; sham operated rats served as controls. Three weeks after surgery, three experimental groups were established: aortocaval shunt and sham operated controls, and aortocaval shunt rats treated with captopril during the last week before the experiments were started. Four weeks after surgery, haemodynamic variables, ANF release, diuresis, and natriuresis were evaluated following a moderate volume expansion. RESULTS: Mean arterial blood pressure was lower in shunt animals and still lower in the ACE inhibited group than in the sham operated controls. Central venous pressure and left ventricular end diastolic pressure (LVEDP) were significantly higher in untreated shunt rats than in their controls. ACE inhibition returned the raised central venous pressure, but not LVEDP, to control values. Shunt rats had lower baseline urinary sodium excretion (UNaV), urinary volume, and packed cell volume than their sham operated controls. ACE inhibition reversed baseline urinary volume to control values. Baseline COOH terminal and HN2 terminal ANF were greatly increased in both treated and untreated shunt rats. Volume expansion was performed three times in conscious animals at 15 min intervals with human plasma protein fraction. Its effect on LVEDP was similar in all three groups, but the increase in central venous pressure was much higher in untreated shunt animals. UNaV, urinary volume, and the release of COOH terminal and NH2 terminal ANF in response to volume expansion were blunted in both treated and untreated shunt rats when compared with their sham operated counterparts. Both absolute and relative heart weights were significantly lower in captopril treated shunt animals than in the untreated shunt group, the latter presenting very significant cardiac hypertrophy. CONCLUSIONS: Aortocaval shunt animals with moderate to severe heart failure show a blunted ANF release and renal response to volume expansion, which, despite significant haemodynamic improvement, are not restored by ACE inhibition. PMID- 8001044 TI - Triggered activity and automaticity in ventricular trabeculae of failing human and rabbit hearts. AB - OBJECTIVE: The aim of the study was to assess the occurrence of triggered activity and automaticity in ventricular trabeculae from failing human hearts and normal and failing rabbit hearts during exposure to a normal and altered extracellular environment. METHODS: Ventricular trabeculae were harvested from failing human hearts (from patients undergoing cardiac transplantation) and from normal and failing rabbit hearts (combined volume and pressure overload). Trabeculae were superfused with normal Tyrode solution followed by a modified Tyrode solution, which mimicked the extracellular milieu in patients with severe heart failure. Modified Tyrode solution contained low potassium (3.0 mM), low magnesium (0.4 mM), and noradrenaline (1 microM). RESULTS: During superfusion with normal Tyrode solution, early afterdepolarisations, delayed afterdepolarisations, and automaticity were not observed in trabeculae from failing hearts. In the modified Tyrode solution, early afterdepolarisations could be induced in 26% of control rabbit and 30% of failing rabbit trabeculae, but never in human trabeculae. During superfusion with the modified solution delayed afterdepolarisations or triggered activity could be induced in 50% of the human failing trabeculae, in 43% of the failing rabbit trabeculae, and in 9% of the normal rabbit trabeculae (p < 0.01); automaticity was observed in 44% of the human trabeculae, and in 7% of the failing rabbit trabeculae, but in none of the control rabbit trabeculae. In failing rabbit myocardium action potential duration was prolonged at cycle lengths > or = 350 ms, but not at shorter cycle lengths. CONCLUSIONS: Delayed afterdepolarisations and automaticity, but not early afterdepolarisations, occur more frequently in myocardium from failing hearts, but only during superfusion with a modified Tyrode solution. This emphasises that the extracellular environment is important with respect to arrhythmogenesis in heart failure, apart from the fixed cellular defect due to heart failure per se. Prolongation of the action potential in failing hearts does not occur at physiological and higher heart rates and therefore cannot be regarded as a protective factor in the prevention of reentrant arrhythmias. The rate of triggered and automatic rhythms was slow. Therefore these mechanisms cannot be responsible for clinical ventricular tachycardias or fibrillation, but may serve as triggers for reentrant arrhythmias. PMID- 8001043 TI - Rapid and slow components of delayed rectifier current in human atrial myocytes. AB - OBJECTIVE: Previous studies in guinea pig heart cells have shown pharmacologically and kinetically distinct components of the classical delayed rectifier current (IK), generally referred to as IKr (rapid IK) and IKs (slow IK). This study was designed to determine whether the human heart contains corresponding components. METHODS: The whole cell voltage clamp technique was used to study IK in single myocytes isolated from human right atrial appendages removed at the time of aortocoronary artery bypass surgery. RESULTS: The activation of IK was best fitted by a biexponential relation, with time constants averaging 204(SEM 20) and 1080(197) ms at +10 mV. IK was inhibited by the specific IKr blocker E-4031 (5 microM), with the drug sensitive and drug resistant components having markedly different kinetic properties. The E-4031 sensitive current activated rapidly, while the drug resistant component activated more slowly, and the activation time courses of E-4031 sensitive and resistant currents paralleled the rapid and slow components of IK between -20 and +50 mV. The E-4031 sensitive component showed strong inward rectification, a half activation voltage (V 1/2) of -14.0(3.3) mV and a slope factor (k) of 6.5(1.5) mV, while the E-4031 resistant current had a linear current-voltage relationship, and values of +19.9(4.2) mV and 12.7(2.5) mV for V 1/2 and k respectively. The envelope of tails analysis showed a time dependent change in IKtail/IKstep under control conditions, and E-4031 strongly reduced the time dependent variation, suggesting that the E-4031 resistant current consisted of one dominant component. CONCLUSIONS: (1) IK in human atrium shows kinetically distinguishable rapid and slow components. (2) These components correspond to E-4031 sensitive and resistant currents. (3) The kinetics and voltage dependence of the rapid (E-4031 sensitive) and slow (E-4031 resistant) components correspond to properties previously described in guinea pig myocytes. These findings have important potential implications for understanding the mechanisms of human atrial repolarisation and its regulation by the autonomic nervous system and antiarrhythmic drugs. PMID- 8001045 TI - The peripheral microcirculation in atrial fibrillation: preservation of capillary pressure and filtration coefficient. AB - OBJECTIVE: The aim was to assess whether atrial fibrillation results in disturbances of capillary pressure and capillary filtration coefficient in man. METHODS: Finger nailfold capillary pressure and calf capillary filtration coefficient were measured in subjects in atrial fibrillation and in matched healthy controls in sinus rhythm. Capillary pressure was measured by direct cannulation using an electronic resistance feedback servonulling technique, and capillary filtration coefficient by mercury-in-Silastic strain gauge plethysmography using a technique believed not to invoke the venoarteriolar response. RESULTS: Mean capillary pressure did not differ significantly between subjects in atrial fibrillation and those in sinus rhythm [18.4(SD 5.1) mm Hg in atrial fibrillation v 18.0(2.9) mm Hg in sinus rhythm]. In a subgroup of patients restored to sinus rhythm (n = 7) by dc cardioversion there was no significant alteration in capillary pressure [15.3(4.2) mm Hg v 16.6(2.8) mm Hg]. Capillary filtration coefficient was also similar in subjects in atrial fibrillation to that in healthy controls in sinus rhythm [2.81(0.65) kfu in atrial fibrillation v 2.87(0.69) kfu in sinus rhythm]. CONCLUSIONS: These data would suggest that under resting conditions autoregulatory mechanisms are able to preserve microvascular homeostasis despite the central changes associated with atrial fibrillation. PMID- 8001046 TI - Big ET-1 infusion in man causes renal ET-1 release, renal and splanchnic vasoconstriction, and increased mean arterial blood pressure. AB - OBJECTIVE: The aim was to study the vascular effects of big endothelin-1 (big ET 1) infusion and its possible conversion to ET-1. METHODS: Six healthy subjects were given an intravenous infusion of big ET-1 in a dose of 8 pmol.kg-1.min-1 for 20 min. Blood samples were taken before, during, and up to 3 h after the infusion from arterial, hepatic, and renal vein catheters for the determination of splanchnic and renal blood flows, as well as ET-1-like immunoreactivity (ET-1-LI) from these vascular beds. RESULTS: Intravenous infusion of big ET-1 was followed by a doubling of arterial ET-1-LI from 4.17(SEM 0.39) to 8.42(0.49) pmol.litre-1 (p < 0.001) and a significant increase in the renal release of ET-1-LI from 1.50(0.18) to 8.68(0.64) pmol.min-1 (p < 0.001) but no splanchnic release. Big ET 1 infusion also caused a decrease in heart rate from 57(4) to 45(3) beats.min-1 (p < 0.001) and an increase in mean arterial pressure from 86(1.3) to 106(3.2) mm Hg (p < 0.001), which lasted for at least 2 h. Renal blood flow fell from 1.38(0.06) to 0.83(0.04) litre.min-1 (p < 0.001) while splanchnic blood flow fell from 1.34(0.11) to 0.83(0.05) litre.min-1 (p < 0.001). CONCLUSIONS: Big ET-1 infusion causes a drop in heart rate, an increase in mean arterial pressure and decreases in splanchnic and renal blood flows. Arterial plasma ET-1 levels doubled and big ET-1 infusion also induced a significantly increased renal, but not splanchnic, release of ET-1-LI, suggesting a unique renal handling of circulating big ET-1. When the results of the infusion of big ET-1 are compared with our previous experiments using ET-1 infusion, more marked haemodynamic changes (as reflected in the increase in mean arterial pressure, the drop in heart rate, and the duration of renal vasoconstriction) are seen despite lower arterial plasma ET-1-LI levels. PMID- 8001048 TI - Anaesthetics alter the magnitude of infarct limitation by ischaemic preconditioning. AB - OBJECTIVE: The aim was to determine whether three commonly used animal anaesthetics alter the magnitude of infarct limitation achieved with ischaemic preconditioning. METHODS: Eighty four anaesthetised non-preconditioned and preconditioned open chest rabbits underwent a 30 min coronary occlusion followed by 3 h reperfusion. Ischaemic preconditioning was achieved with 5 min coronary occlusion beginning 15 min before the 30 min coronary occlusion. The anaesthetics studied were: pentobarbitone (30 mg.kg-1 intravenously +30-50 mg.kg-1.h-1 intravenously), isoflurane (1.5-2.5% end expiratory), and ketamine/xylazine (cocktail of 67 mg ketamine and 6.7 mg xylazine.ml-1, 1 ml.kg-1 intramuscularly +0.3-1.3 ml.kg-1.h-1 intramuscularly). Area at risk was delineated with ZnCdS particles and infarction assessed with tetrazolium. RESULTS: There were no significant differences in area at risk, heart rate, arterial pressure, and temperature between non-preconditioned and preconditioned hearts. Although infarct size was not significantly different among non-preconditioned hearts for each anaesthetic regimen (p = NS), the magnitude of infarct limitation with preconditioning varied with the anaesthetic employed (decrease in infarct size from control values of 81%, 44%, and 33% for pentobarbitone, isoflurane and ketamine/xylazine, respectively, p = 0.0145 for comparison of the three magnitudes, two factor ANOVA). CONCLUSION: Anaesthetic regimens affect the degree of infarct size limitation seen with ischaemic preconditioning. PMID- 8001047 TI - Alterations in angiotensin II receptor mediated signal transduction shortly after coronary artery constriction in the rat. AB - OBJECTIVE: The aim of the study was to determine the effect of coronary artery constriction on the density of angiotensin II receptors and on the effector responses coupled with these receptors on myocytes one week after surgical induction of coronary artery stenosis in rats. METHODS: After induction of coronary artery stenosis and following the estimation of global cardiac performance, myocytes were enzymatically dissociated and radioligand binding studies were performed. In addition, the isotonic contractile performance, cytosolic calcium transients, and angiotensin II stimulated inositol phosphate generation in myocytes were measured in the presence and absence of the angiotensin II receptor subtype antagonist losartan. RESULTS: After documenting left ventricular failure and right ventricular dysfunction, the expression and density of angiotensin II receptors in left ventricular myocytes were evaluated and found to be increased 3.1-fold and 4.1-fold, respectively. Corresponding increases in right ventricular myocytes were 3.6-fold and 4.5-fold. In contrast, the quantity of the regulatory protein Gq alpha was not altered in either ventricle. Angiotensin II did not increase the generation of total inositol phosphates in left and right ventricular myocytes at maximum stimulation. However, the threshold for the formation of inositol phosphates was lowered in left ventricular myocytes of coronary narrowed rats. Measurements of single cell mechanics indicated that angiotensin II stimulation markedly improved the depression in myocyte function biventricularly. This inotropic effect was coupled with the restoration of cytosolic calcium. CONCLUSIONS: The upregulation of angiotensin II receptors on myocytes in this model of global ischaemia may be a compensatory mechanism ameliorating myocyte contractility in an attempt to sustain ventricular pump function. PMID- 8001049 TI - Increased collagen synthesis and decreased collagen degradation in right ventricular hypertrophy induced by pressure overload. AB - OBJECTIVE: The aim was to examine the effect of pressure overload in rabbits on ventricular collagen metabolism and procollagen gene expression. METHODS: Right ventricular hypertrophy was induced by banding the pulmonary artery such that the diameter of the vessel was reduced by 50%, and animals killed in groups after two and 14 days. Collagen synthesis and degradation of newly synthesised collagen were assessed following a single intravenous injection of 3H-proline with a flooding dose of non-radioactive proline, given 3 h before the animals were killed. Northern and slot blot analyses were performed to measure procollagen alpha 1(I) mRNA. RESULTS: The fractional collagen synthesis rate increased sixfold in the right ventricle only 2 d after pulmonary artery banding (p < 0.001), then fell to just over double the control value by 14 d (p < 0.05 from control). The proportion of newly synthesised collagen degraded decreased from 50.7(SD 12.8)% to 26.8(15.8)% in 2 d (p < 0.05) and remained at this level. The procollagen alpha 1(I) mRNA level increased by more than fourfold in the right ventricle 2 d after the onset of pressure overload, and was less than three times control levels at 14 d. CONCLUSIONS: The development of right ventricular hypertrophy is associated with a rapid increase in collagen production, with regulation at multiple sites in the biosynthetic pathway. This regulation occurs at both transcriptional and post translational levels. PMID- 8001050 TI - Cardioprotective effects of platelets against ischaemia-reperfusion injury are related in part to platelet glutathione redox cycle. AB - OBJECTIVE: Washed platelets have been shown to protect isolated buffer perfused rat hearts from injury and dysfunction following ischaemia-reperfusion. This study was designed to investigate whether platelet glutathione redox cycle contributes to the protective effect of platelets. METHODS: Isolated rat hearts were perfused with Krebs-Henseleit buffer alone, buffer containing platelets, or buffer containing platelets pretreated with inhibitors of glutathione redox cycle. All hearts were subjected to 40 min of global ischaemia followed by 30 min of reperfusion. RESULTS: Following ischaemia and reperfusion, hearts perfused with buffer alone showed a marked reduction in force of cardiac contraction and heart rate, an increase in coronary perfusion pressure and diastolic tone, and a release of creatine kinase in the coronary effluent. Myocardial creatine kinase, superoxide dismutase activity, and glutathione content all fell. Perfusion of hearts with washed platelets provided significant protection from ischaemia reperfusion related myocardial injury and dysfunction. The cardioprotective effects of platelets were attenuated when they were preincubated with the glutathione redox cycle inhibitors dehydroepiandrosterone, 1,3-bis (2 chloroethyl)-1-nitrosurea, or 1-chloro-2,4-dinitrobenzene. Pretreatment of platelets with glutathione redox cycle inhibitors did not affect the platelet mediated preservation of myocardial superoxide dismutase activity. CONCLUSIONS: Platelet glutathione redox cycle contributes in part to the cardioprotective effects of platelets against ischaemia-reperfusion injury and dysfunction in the isolated rat heart. PMID- 8001051 TI - Brushing-induced effects with and without a non-fluoride abrasive dentifrice on remineralization of enamel surfaces etched with phosphoric acid. AB - The remineralization of acid-etched enamel after brushing with and without a non fluoride abrasive dentifrice was investigated using scanning electron microscopy after sodium hypochlorite (NaOCl) or ethylenediamine tetra-acetic acid treatment, of the specimens. Ground enamel pieces were etched with 30% phosphoric acid for 60 s and attached to resin plates. They were exposed to the oral environment of 4 subjects for 8 weeks and brushed for 1 min daily. Paste and brushing caused the acid-etched enamel to erode selectively, i.e., deep grooves were formed in the prism peripheral regions, while projections of the prism bodies showing a relatively low density of crystallites were retained. Brushing without dentifrice, on the other hand, caused about 0.5 micron thick pellicle with tag like structures to cover the etched enamel. Fine mineral granules, presumably derived from saliva and minute fragments of etched crystallites, were precipitated on the enamel surface as a thin layer with the pellicle. These results indicate that daily brushing without dentifrice induces the remineralization of acid-etched enamel by depositing salivary components, while paste brushing will lead to abrasion of the weakened enamel. PMID- 8001052 TI - An in vitro model for studying the efficacy of fluoride dentifrices in preventing root caries. AB - This investigation tested and validated an in vitro model for studying the effects of fluoride on human dentin mineral content and fluoride uptake. Four studies examined the effects of different concentrations of fluoride, established dose-response profiles with NaF and Na2PO3F, and tested commercial dentifrices. A 7- or 14-day cyclic treatment regimen involved four 1-min exposures of sound human dentin specimens to the treatment agents, a 4-hour acid challenge period, and 20 h in human saliva daily. Mineral content was analyzed by image analysis microradiography and fluoride assays were performed using a microdrill biopsy technique. Data from these studies established the ability of the in vitro model to provide reproducible results, to demonstrate significant dose-related differences in the effects of both NaF- and Na2PO3F-containing treatments on dentin fluoride uptake and demineralization, and to detect a fluoride-induced reduction in dentin caries, relative to a nonfluoride control, similar to results established in a clinical trial. PMID- 8001054 TI - The effect of mineral-derived zinc ions on in vitro glucose metabolism of Streptococcus mutans NCTC 10449. AB - Mouthrinses containing zinc ions inhibit plaque acidogenicity, but the effect is transient. Zinc-containing apatite or zinc phosphate precipitated within dental plaque might serve as a reservoir for zinc ions, thus providing prolonged inhibition of acid formation. Zinc-containing fluorhydroxyapatite was prepared from solutions containing CaCl2, KH2PO4, NaF and increasing amounts of ZnCl2 (0.0, 0.005, 0.02, 0.1, 0.2 or 1 mM; minerals No. 1-6, respectively) by raising the pH with ammonia. Zinc phosphate tetrahydrate (mineral No. 7) was prepared in a similar manner from a solution containing ZnCl2 and KH2PO4 only. Dense cell suspensions of Streptococcus mutans NCTC 10449 were incubated with 14C-glucose and one of the test minerals (No. 1-7). Glycolysis was allowed to proceed, with or without pH control, in a pH-stat. Samples were withdrawn at 1, 2, and 3 min, and extracellular glycolytic metabolites were identified by HPLC. Mineral No. 7 inhibited glycolysis and any pH fall almost completely. With the pH fixed at 5.5, reduction of glucose consumption and lactate formation was 83 and 93%, respectively, compared to the no-zinc control mineral (No. 1). No changes in glucose consumption or lactate formation were evident in the presence of minerals No. 2-6. All apatitic minerals had a buffering effect and, in the absence of pH control, glycolysis was increased due to the higher pH. Detectable levels of fluoride were not released by any mineral into the incubation mixture, and zinc only by minerals No. 6 and 7 in greater than trace amounts.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8001053 TI - Fluoride uptake and release characteristics of glass ionomer cements. AB - The aims of this study were firstly to investigate the fluoride-releasing characteristics of five commercial glass ionomer materials: Ketac Fil, Chemfil Superior, Fuji II LC, Aquacem and Vitrebond. The second aim was to assess the fluoride uptake and subsequent release from the same range of materials. In both tests, ten discs, 6 mm in diameter with a thickness of 1.5 mm, were made for each material. The initial fluoride release was assessed over a 60-day period for all materials. Each disc was immersed in 2 ml of de-ionised water within a plastic vial. The solutions were changed daily up to day 15, and thereafter every 3 and 4 days until the end of the test. All of the materials released measurable amounts of fluoride throughout the test period, with a considerable range on day 1 (15.3 155.2 ppm F). The concentration of fluoride released on the 2nd day fell sharply for all materials (range 6.3-44.3 ppm F). By day 60 all materials continued to release fluoride, albeit to a lesser extent (range 0.9-3.99 ppm F). With regard to the uptake and release of fluoride, a similar protocol was employed, although all samples were immersed in 1 litre of de-ionised water for 60 days to allow the majority of the fluoride to leach out from the materials. The ten pellets for each material were divided into two groups, five samples as control and five samples as test. Each day over a 20-day period all test samples were exposed to a 1000-ppm F solution for 2 min.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8001055 TI - Effects of subinhibitory concentrations of chemical agents on hydrophobicity and in vitro adherence of Streptococcus mutans and Streptococcus sanguis. AB - The aim of this investigation was to determine whether sublethal concentrations of chlorhexidine (Cx), hexetidine (Hx), cetylpyridinium chloride (Cc), sodium dodecyl sulfate (SDS), sanguinarine (Sg), sodium fluoride (NaF), and ammonium fluoride (NH4F) could affect hydrophobicity and adhesion of Streptococcus sanguis and Streptococcus mutans to saliva-coated hydroxyapatite (S-HA). Determination of the minimum inhibitory concentrations (MICs) showed that both species were susceptible to all agents tested. Growth in the presence of sub-MIC concentrations of Cx, SDS, Cc, NaF, or NH4F did not change significantly the hydrophobicity of S. sanguis cells when compared to the control which lacked any agent. However, growth in the presence of Hx or Sg resulted in a significant reduction in their hydrophobicity. Sub-MIC levels of SDS or Sg in the growth medium resulted in S. mutans cells with increased affinity for hexadecane compared with the control. The adherence of S. sanguis was changed significantly only by Hx or Sg, resulting in less cells adhering to S-HA. However, S. mutans cells previously incubated with NaF, NH4F, or Sg showed a higher adherence to S HA than the control. The mechanisms of interference with adherence are at present not completely understood. Thus, antimicrobial agents at sub-MIC concentrations can interfere selectively with hydrophobicity and/or adhesion of oral streptococci. PMID- 8001056 TI - Composition and flow rate of saliva and caries development in young rats following administration of lithium. AB - Lithium carbonate (Li2CO3), an antipsychotic medication, was investigated to determine the effects on the stimulated flow and composition of saliva and on caries development in rats. Lithium carbonate was delivered via osmotic pumps at 10, 15 and 60 mg/kg/day. All animals were infected with Streptococcus sobrinus 6715 and fed a cariogenic diet. Lithium administration exerted a caries protective effect on sulcal surfaces, though the reduction in caries scores was statistically significant only for the groups receiving Li2CO3 at 10 and 60 mg/kg/day compared to control animals (p +/- 0.05, ANOVA). There were no detectable alterations in protein concentration, electrophoretic profiles, or flow rates of stimulated parotid and submandibular saliva associated with the decreased sulcal caries incidence. Weight gain, water consumption and the populations of total cultivable flora recovered were not influenced by the administration of lithium. Investigation into the mechanisms of the sulcal caries reduction will require further exploration of changes caused by lithium on salivary gland function. PMID- 8001057 TI - Intra- and inter-individual differences in salivary sucrose clearance over time. AB - Salivary clearance of sugars influences acid production of dental plaque. The aim of the present study was to follow the clearance of sucrose over time. Ten subjects participated in five or six experiments each during a period of 20 months. The subjects rinsed with a 20% sucrose solution. Before the rinse and after 2, 5, 10 and 30 min a saliva sample was collected. The salivary sucrose concentration was determined by an enzymatic technique. As a measure of the clearance of sucrose in saliva, the area under the concentration versus time curve (AUC) was used. Analysis of variance revealed no differences with time in the intra-individual AUC. However, the differences in AUC among individuals were highly significant (p < 0.001). The results show that the clearance pattern of sucrose may be an individual property which is constant over long time periods. PMID- 8001058 TI - The video camera compared with the densitometer as a scanning device for microradiography. AB - In the recent past image analysis systems, comprising a video (CCD) camera and dedicated software, have replaced densitometer-based systems to analyze mineral content profiles using transversal microradiography (TMR). The main reasons for the introduction of the CCD camera were the ease and speed at which it can be operated. The densitometer, as a scanning device for TMR, has in the recent years been validated and is in this study considered as 'gold standard'. Comparisons of the two scanning devices for measuring the optical density of microradiograms have never been reported in the literature. The focus of this study was on accuracy and reproducibility of the scanning devices with the emphasis put on possible limitations of the CCD camera relative to the densitometer. These include resolution, number of gray levels and homogeneity of illumination of the scan area. The microscope was arranged in such a way that the same area on the microradiogram could be assessed by both scanning devices. Three different types of lesions were analyzed: a subsurface lesion, a surface-softened lesion and a laminated lesion. Paired t tests showed no significant difference between the mineral content profiles produced by the two scanning devices. The integrated mineral loss values were calculated and compared with analysis of variance and showed no significant differences. It is therefore concluded that mineral content profiles and integrated mineral loss obtained by the CCD camera are as accurate and reproducible as those obtained by the densitometer. PMID- 8001059 TI - In vitro comparison of D- and E-speed film radiography, RVG, and visualix digital radiography for the detection of enamel approximal and dentinal occlusal caries lesions. AB - The aims of this study were (1) to compare the accuracy of conventional D- and E speed film radiography and direct digital radiography using the RadioVisioGraphy and Visualix systems for the detection of enamel approximal caries lesions and (2) to compare the accuracy of D- and E-speed films and the Visualix system for the detection of dentinal occlusal caries lesions. In total, 122 approximal surfaces were examined in vitro by 3 observers and 65 occlusal surfaces by 2 observers. The true caries diagnosis was based on histological assessment of the surfaces after sectioning the teeth. Approximal surfaces were deemed diseased by the presence of a demineralization in enamel, while occlusal surfaces were deemed diseased by the presence of a demineralization into dentine. The diagnostic accuracy for each radiographic method was expressed as a receiver operating characteristic (ROC) curve area. For the approximal surfaces, the areas under the ROC curves ranged from 0.53 (Visualix) to 0.70 (E-speed film). For the occlusal surfaces, the areas ranged from 0.62 (Visualix) to 0.79 (D- and E-speed films). No statistically significant differences between mean ROC curve areas for the radiographic methods were found either for the approximal or for the occlusal surfaces. It was concluded that radiography was of almost no value in the detection of enamel approximal caries lesions, but of some value in the detection of dentinal lesions in occlusal surfaces. PMID- 8001061 TI - Impact of the validator and the validation method on the outcome of occlusal caries diagnosis. AB - In studies evaluating the performance of caries-diagnostic methods, a validation of the true state of disease is needed. The aim of this study was to evaluate the impact of the validator and the validation system (stereomicroscopy or radiography of tooth sections) on the outcome of diagnostic tests for occlusal caries. The material consisted of 60 extracted third molars which were serially sectioned (500-600 microns thick). Four observers examined the sections by two caries validation methods: stereomicroscopy and film radiography. The presence of caries in the occlusal surfaces of these teeth had previously been recorded by visual inspection and conventional film radiography. The kappa values for interobserver agreement within one validation method ranged from 0.44 to 0.76 for radiography and from 0.47 to 0.60 for microscopy. The intraobserver agreement with the two methods was low (range 0.31-0.49), and by cross-tabulating the data, it was found that the disagreements originated in a consistently deeper lesion score with stereomicroscopy than with radiography by all observers except 1. By use of receiver operating characteristic curve areas, little impact of the validation method was seen when visual inspection was validated (against microscopy mean area = 0.75, against radiography mean area = 0.74). The mean receiver operating characteristic area was higher when diagnostic film radiographs were validated against radiography (0.68) than against microscopy (0.63). The differences between observers within a validation method were larger with microscopy than with radiography. In conclusion, caries validation methods are subject to variability. The outcome of caries--diagnostic tests may be influenced both by the validator and the validation method. PMID- 8001060 TI - Clinical diagnosis of occlusal dentin caries. AB - An occlusal restoration is usually considered necessary when a lesion extends into the dentin. This study aimed to assess the relationship between the clinical appearance of occlusal caries and the lesion depth. Special attention was paid to differentiate the inner, partly demineralitzed layer of carious dentin that should be preserved from the outer carious layer that should be removed before placing a restoration. Fissures in extracted premolars and molars were classified clinically by the authors. The mean pairwise interobserver agreement, weighted Cohen's kappa (kappa), was 0.73, which indicated 'substantial agreement'. The depth of zones revealing softness by probing and/or discoloration was assessed on ground surfaces. Of the carious fissures that were scored sound by clinical examination (n = 17), 76% revealed enamel lesions on the ground surfaces. Of those occlusal surfaces with a discoloration only but no cavitation (n = 57), 13 showed dentin lesions, but only 5 of these revealed softness by probing. Of those lesions with very small cavitations (n = 60), 19 were confined to enamel, 41 showed dentin lesions and of these 32 revealed softness by probing. All but 1 of the lesions with small cavitations (n = 28) showed dentin involvement and all but 2 of these revealed softness. If cavitation in the occlusal lesion was used as a criterion for identifying dentin lesions with softness, the sensitivity and specificity values were 0.92 and 0.69, which means a relatively high frequency of overregistration. PMID- 8001062 TI - Dental caries changes between 1982 and 1991 in children aged 6-12 in Athens, Greece. AB - The aim of this study was to compare dental caries and oral hygiene status in children aged 6-12 years in the Athens area between 1982 and 1991. Dental examinations were carried out by the same examiners in 773 children attending the same randomly selected schools sited in areas of different socioeconomic levels. The findings concerning the deciduous dention showed that the percentage of caries-free children increased in 1991 compared to 1982 by 38%. The mean deft scores were reduced by an amount ranging from 21 to 34%. Changes in caries prevalence were also observed in the permanent dention. The percentage of caries free children for the total examined population increased by 94% while the reduction in DMFT index ranged between 38 and 70%. Treatment need was significantly lower in 1991 compared to 1982 in both dentitions. Debris index scores were similar while oral hygiene habits had slightly improved by 1991. The decline in caries levels may be attributed to the increased use of various forms of fluoride. Furthermore, dental health awareness of the population has improved. PMID- 8001063 TI - Association between dental enamel opacities and dental caries in a north Wales population. AB - This study examined the association between enamel opacities and dental caries in a population from North Wales with low levels of fluoride in the drinking water. Those subjects with only diffuse (n = 317) types of opacity had a mean DMFS of 1.6 (+/- 3.4) compared with those having only demarcated (n = 1,408) opacities of 3.4 (+/- 4.3). The group with both (n = 317) types of defect present had a DMFS of 2.4 (+/- 3.7) and the group with no defects (n = 1,496) had a DMFS of 2.7 (+/- 3.8). These differences were statistically significant (p < 0.001). Possible reasons for these differences are discussed. PMID- 8001064 TI - Caries incidence, salivary flow rate and efficacy of fluoride gel treatment in irradiated patients. AB - The caries-preventive effect of daily applications of a fluoride gel was studied in 55 patients receiving radiotherapy for tumors of the head and neck. The study was designed as a randomized, double-blind study with two parallel groups. From the start of radiotherapy one group received a 0.42% F gel once a day for 1 year. The other group received a daily application of a 1.23% F gel for 4 weeks followed by the use of the 0.42% F gel daily for 1 year. The results showed that in patients with an unstimulated saliva flow of > 0.1 ml/min daily fluoride gel treatment with a fluoride concentration of 0.42% F was sufficient to inhibit caries almost completely. The use of the 1.23% F gel was not superior to the 0.42% gel treatment program alone. In an attempt to evaluate the salivary flow rate as a diagnostic criterion for increased caries risk, sensitivity and specificity were evaluated. It was found that with an unstimulated saliva flow rate of < 0.1 ml/min the positive predictive value was 80%. The corresponding value for stimulated salivary flow rate of < 0.5 ml/min was 85%. One can therefore predict that 80% of patients with flow rates < 0.1 ml/min will develop at least one carious lesion per year. The corresponding negative predictive value for unstimulated saliva flow > 0.1 ml/min was 75%. That means that 75% of patients using the 0.42% F gel daily and with at least some saliva secretion will not develop any new carious lesions. PMID- 8001065 TI - Effect of a 3-year professional flossing program with chlorhexidine gel on approximal caries and cost of treatment in preschool children. AB - The aim was to evaluate the effect of chlorhexidine gel treatment on the incidence of approximal caries in preschool children. One hundred and seventeen 4 year-olds, divided into two groups, participated: (1) chlorhexidine gel group (n = 59), and (2) placebo gel group (n = 58). Group 1 was treated 4 times a year with a 1% chlorhexdine gel and group 2 with a placebo gel. Approximately 0.7 ml of gel was applied interdentally by means of a flat dental floss. A control group (group 3), which did not receive any flossing or gel treatment, was also included in the study (n = 116). After 3 years, i.e. when the children were 7 years old, the mean incidence of caries on approximal surfaces (defs), including both enamel and dentin lesions, was 2.59 in the chlorhexidine gel, 4.53 in the placebo gel and 4.20 in the control group (group 1 vs. 2 and group 1 vs. 3: p < 0.01). Mean number of approximal fillings at the end of the study, i.e. when the children were 7 years old, was 0.33 in the chlorhexidine gel, 1.04 in the placebo gel and 0.80 in the control group (group 1 vs. 2: p < 0.01; group 1 vs. 3: p < 0.05). The progression of approximal caries lesions, diagnosed on bitewing radiographs from the age of 5 to 7, was slower in the chlorhexidine than in the placebo gel group (the control group was not evaluated in this respect). A cost analysis, based on the total treatment time in minutes, showed a small gain for the flossing program.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8001066 TI - [40 years' of the 2nd Medical School of Charles University in Prague]. PMID- 8001067 TI - [The Scientific Conference of the 2nd Medical School of Charles University in Prague held 25 October 1993]. PMID- 8001068 TI - [Heraldic signs of the 2nd Medical School of Charles University in Prague]. PMID- 8001070 TI - [Research at the Medical School of Charles University]. PMID- 8001069 TI - [On departing from the Medical School Hospital Pod Petrinem]]. PMID- 8001071 TI - [Quo vadis facultas medica secunda (Pragensis)?]. PMID- 8001072 TI - [Molecular biology and medicine: hopes and risks]. PMID- 8001073 TI - [Developmental medicine]. PMID- 8001075 TI - [Medicine and culture]. PMID- 8001074 TI - [Medicine and the arts]. PMID- 8001076 TI - Macrophages within the human adrenal gland. AB - There is increasing evidence for an immune-adrenal interaction in which macrophages may play an important role. However, few data are available with respect to a human intra-adrenal macrophage system. In this study, we have investigated the density, distribution and phenotype of human adrenal macrophages using monoclonal antibodies. Macrophages are localized in all zones of the adrenal gland. These cells exhibit the phenotype of the phagocytotic macrophage compartment (CD11c+, KiM8+). At the ultrastructural level, macrophages are frequently attached to the endothelial wall, but also lie in direct contact with cortical and chromaffin cells. This investigation reveals the cellular basis for the possible role of macrophages in the local immune-neuroendocrine axis. PMID- 8001077 TI - Distribution of beta 2-like adrenergic receptors in the cnidarian Renilla koellikeri as revealed by autoradiography and in situ hybridization. AB - Autoradiography and in situ hybridization were used to examine the histological distribution of the previously characterized beta 2-like adrenergic receptors involved in the bioluminescent activity of the sea pansy Renilla koellikeri. The use of [3H]-(+/-)CGP12177 as radioligand revealed autoradiographic labelling of the refringent granule-filled endoderm at the base of autozooid tentacles and autozooid columns, and in the corresponding endoderm of siphonozooid polyps, all areas where photocytes are concentrated. The presence of excess (10 microM) unlabelled (+/-)CGP12177 or atenolol in the incubation mixture substantially reduced total [3H]-(+/-)CGP12177 labelling. Under low stringency hybridization washing, human beta 2-adrenoceptor oligonucleotide probe signals were detected in granular cells located in those areas of polyp endoderm that were labelled by [3H]-(+/-)CGP12177. These cells were previously shown to be distinct from, but in close proximity to photocytes. No other cell or tissue type was labelled in polyps or throughout colonial tissues. The results suggest that a conserved form of beta 2-adrenergic receptors is present and synthesized in a unique type of endodermal cell indirectly involved in sea pansy bioluminescence control. PMID- 8001078 TI - Alterations in the subcellular distribution of 17 beta-estradiol dehydrogenase in porcine endometrial cells over the course of the estrous cycle. AB - The uteri of German landrace gilts slaughtered at different days of the cycle were processed for immunocytochemistry and biochemical analyses. Plasma was collected for hormone assays. The monoclonal antibody F1 against the structure bound 17 beta-estradiol dehydrogenase of porcine endometrial epithelium was applied to rehydrated paraffin sections either as a direct, peroxidase-linked probe or in combination with a fluorescing secondary antibody. The oxidation of estradiol was measured in homogenates of tissue powdered in liquid nitrogen. Immunoreactivity was restricted to endometrial epithelium. In the glandular epithelium, faint dots of fluorescence became visible at day 4, which apparently coalesced to spherical structures of 2-4 microns diameter at the cell basis between days 11 through 17 before disappearing by day 18. A similar distribution was observed for the oxidation products of diaminobenzidine beginning with a faint uniform staining and followed by the appearance of intensely stained basal bodies persisting until day 17. Essentially the same time course was seen in the luminal epithelium but with a different distribution. Immunoreactive material amassed in the apical region of the cells, but the conspicuous aggregations were absent. Time course and intensities of the immunological responses are matched by the enzymatic activity measured in parallel. Both correlate with the plasma progesterone levels, suggesting an induction of the enzyme by the hormone. An involvement of the cytoskeleton in the sequence of subcellular distribution patterns is discussed. PMID- 8001079 TI - Three patterns of distribution characterize the organization of endothelial microfilaments at aortic flow dividers. AB - Since actin microfilaments are essential in the maintenance of endothelial integrity and in the repair of injured endothelium, we have carried out a detailed study of the distribution of microfilaments in the immediate vicinity of aortic branches. Branches are of major interest because there is a predilection for atherosclerotic lesions near branch ostia. We made an extensive, systematic examination of branches of the aorta and iliac arteries using in situ staining of perfusion-fixed arteries. Microfilaments were localized using rhodamine phalloidin. Three patterns of staining were observed. Some endothelial cells showed prominent central stress fibers. Others had few central stress fibers but prominent peripheral fibers. Still others showed an intermediate pattern with some central and some peripheral fibers present. At small branch sites, the lip of the divider was more blunt, and there were more cells with peripheral actin. At large branches, cells with peripheral actin were confined mainly to the lip, while there were many more cells with prominent central fibers. We also found that major differences can occur over very small distances, so adjacent cells may have strikingly different patterns of microfilament distribution. These patterns appear to reflect the geometry of the flow divider and local variations in hemodynamic shear stress. The differences in microfilament distribution may reflect differences in endothelial functions which are essential in maintaining endothelial integrity. PMID- 8001080 TI - Neuronal differentiation in vitro from precursor cells of regenerating spinal cord of the adult teleost Apteronotus albifrons. AB - This study documents neuronal differentiation in vitro from undifferentiated precursor cells of caudalmost regenerating spinal cord of the teleost Apteronotus albifrons. At 11 days in vitro, cells from the caudalmost tip of the regenerating cord are flat and polygonal in shape, lack neuronal processes and do not stain with antibody against neuron-specific filaments. At 15 days in vitro, some of the caudalmost cells have developed short, neurite-like processes; at 18 days in vitro, some cells react positively with antibody against neuron-specific filaments. At 26 days in vitro, many of the caudalmost cells have long branching neurites and react positively with anti-neurofilament antibody. Addition of insulin-like growth factor-I to the medium accelerates the process of neuronal differentiation from the caudalmost precursor cells in vitro. The source of these precursor cells is ultimately cells of the ependymal layer of adult spinal cord. Further investigation of the factors that control production and differentiation of these cells will be important in defining the developmental potential possible for vertebrate spinal cord cells and may aid in creating an optimal environment for regeneration of axons within mammalian spinal cord. PMID- 8001081 TI - Immunohistochemical and histochemical evidence for the presence of noradrenaline, serotonin and gamma-aminobutyric acid in chief cells of the mouse carotid body. AB - The immunohistochemical study revealed tyrosine hydroxylase (TH), dopamine beta hydroxylase (DBH), phenylethanolamine N-methyltransferase (PNMT), serotonin, glutamate decarboxylase (GAD) and gamma-aminobutyric acid (GABA) immunoreactivities in the mouse carotid body. TH and DBH immunoreactivities were found in almost all chief cells and a few ganglion cells, and in relatively numerous varicose nerve fibers of the carotid body. The histofluorescence microscopy showed catecholamine fluorescence in almost all chief cells. However, no PNMT immunoreactivity was observed in the carotid body. Serotonin, GAD and GABA immunoreactivities were also seen in almost all chief cells of the carotid body. From combined immunohistochemistry and fluorescence histochemistry, catecholamine and serotonin or catecholamine and GABA were colocalized in almost all chief cells. Thus, these findings suggest that noradrenaline, serotonin and GABA may be synthesized and co-exist in almost all chief cells of the mouse carotid body and may play roles in chemoreceptive functions. PMID- 8001082 TI - Morphological studies by light and electron microscopy of pancreatic acinar cells under the effect of Tityus serrulatus venom. AB - We studied in vivo and in vitro morphological aspects of pancreatic acinar cells after treatment with Tityus serrulatus venom (TSV). After three hours in an in vitro system, positive secretagogue effects of the venom were identifiable both at the light-microscopic (LM) and the electron-microscopic (EM) levels. At 1 microgram/ml TSV, maximal secretion (as measured in a concomitant radiolabeling dose-response experiment) of exocrine proteins at 58% was manifest as a discharge of most zymogen granules (ZG) and consequent appearance of secretory material in acinar lumina. At the supramaximal dose of 10 micrograms/ml TSV, exocytotic images were often observed also with secretory contents previously discharged. The lowest dose of venom at 0.01 microgram/ml caused no stimulation of zymogen discharge above resting secretion levels; however, morphological changes were observed. At high doses of TSV, both in vivo and in vitro, large aggregates associated with the cis-Golgi develop between this region and the endoplasmic reticulum (ER). Since Tityus venoms have been associated with causation of pancreatitis, we were interested in comparisons of our experimental tissue with parameters attributed to development of the disease. Our studies have demonstrated considerable evidence that large intracellular vacuoles, discharged ZG, effaced acinar lumina with disappearance of microvilli and other manifestations of possible early events in pancreatitis are indeed frequently observed both in pancreatic lobules in vitro and in whole pancreas in vivo when exposed to TSV. PMID- 8001083 TI - Expression of vacuolar H(+)-ATPase in osteoclasts and its role in resorption. AB - By means of light- and electron-microscopic immunocytochemistry, we have demonstrated the expression of vacuolar H(+)-ATPase in mouse osteoclasts. In fully differentiated osteoclasts, intense immunolabeling was observed along the plasma membranes including those of ruffled borders and associated pale vesicles and vacuoles, whereas those of clear zones and basolateral cell surfaces were entirely free of immunoreaction. Specific expression of vacuolar H(+)-ATPase was also detected over polyribosomes and cisterns of the rough-surfaced endoplasmic reticulum. Multinucleated osteoclastic cells were suspended on dentine slices and cultured for 48 h in the presence or absence of either concanamycin B or bafilomycin A1, specific inhibitors of vacuolar H(+)-ATPase. Morphometric analysis of co-cultured dentine slices with backscattered electron microscopy revealed that both inhibitors strongly reduced the formation of resorption lacunae in a dose-dependent manner. These results suggest that vacuolar H(+) ATPase is produced in the rough-surfaced endoplasmic reticulum, stored in the membrane vesicles, and transported into the ruffled border membranes of osteoclasts, and that this enzyme plays a key role in the creation of an acidic subosteoclastic microenvironment for the demineralization of co-cultured substrates. PMID- 8001084 TI - Immunohistochemical analysis of EGF in epiphyseal growth plate from normal, hypophysectomized, and growth hormone-treated hypophysectomized rats. AB - Epiphyseal growth plate cartilages from the proximal tibia of normal, hypophysectomized, and growth hormone (GH)-treated hypophysectomized rats were subjected to immunohistochemistry for detection of epidermal growth factor (EGF). In the normal growth plate, EGF was distributed mainly in the proliferative zone. Hypophysectomy resulted in considerable atrophy of the chondrocytes and the cartilage matrix (a decreased number of mature-type chondrocytes and a decreased ratio of proliferating to hypertrophic chondrocytes) and a significant diminution of EGF immunoreactivity. Treatment with GH reversed these effects of hypophysectomy, causing an increased thickness of the growth plate and EGF reactive sites in all chondrocyte layers. The most intense immunostaining for EGF, however, was frequently seen in the nuclei of chondrocytes with flattened appearance. It appears that EGF could be incorporated or synthesized in chondrocytes having marked mitogenic activity. The present results, taken with previous data on EGF involvement in growth of cartilaginous tissue in vivo and in vitro, strongly suggest that EGF-immunoreactive chondrocytes are involved in cartilage proliferation and growth under the specific influence of GH. PMID- 8001085 TI - An early decrease in interphotoreceptor retinoid-binding protein gene expression in Abyssinian cats homozygous for hereditary rod-cone degeneration. AB - Levels of interphotoreceptor retinoid-binding protein (IRBP) protein and message in retinas of Abyssinian cats homozygous for progressive rod-cone degeneration were determined at early ages, well before the onset of clinical retinal degeneration. IRBP gene expression was assessed by immunochemical quantitation of IRBP protein, and by Northern blotting and slot-blotting of total RNA using a human IRBP cDNA probe. Morphology was assessed by electron microscopy and immunocytochemistry. Levels of both IRBP protein and message in affected Abyssinian cat retinas were significantly reduced below normal as early as 4 weeks of age at the earliest stage of retinal disorientation. Opsin mRNA was more abundant in affected Abyssinian cat retinas than in control retinas. This was at least 1 year before the onset of clinical symptoms. The reduction in IRBP gene expression to levels significantly below normal well before the onset of retinal degeneration in affected Abyssinian cat retinas indicates that this represents a primary defect or at least an early problem that could itself cause adverse effects. PMID- 8001086 TI - Taurine, amino acid transmitters, and related molecules in the retina of the Australian lungfish Neoceratodus forsteri: a light-microscopic immunocytochemical and electron-microscopic study. AB - The morphology of the retina of the Australian lungfish Neoceratodus forsteri was investigated by means of light- and electron microscopy, whilst immunocytochemical studies were performed to determine the cellular distributions of the major amino acid neurotransmitters and other amino acids. The distributions of glycine and GABA were similar to those previously described for teleost, amphibian and mammalian retinae. Labelling was abundant in amacrine cells, whilst GABA was also present in one layer of horizontal cells and some bipolar cells. Taurine was present in both rods and cones, but, unlike the mammalian or avian retina, was absent from other cellular structures, including glial elements. Unexpectedly, the photoreceptor terminals lacked an apparent content of the excitatory amino acid transmitter glutamate. The glutamate that was present in the rods and cones occupied a crescentic arc corresponding to the location of glycogen-rich paraboloids. Asparagine was also present in rods, albeit in the modified mitochondria that formed the elipsoids of the rod inner segments. Arginine, the precursor for formation of nitric oxide, was present in glial cells, and in the paraboloids of both rods and cones. PMID- 8001087 TI - Cytoplasmic granule formation in mouse pancreatic acinar cells. Evidence for formation of immature granules (condensing vacuoles) by aggregation and fusion of progranules of unit size, and for reductions in membrane surface area and immature granule volume during granule maturation. AB - We used a computer-assisted morphometry approach to analyze quantitatively the process of cytoplasmic granule formation in mouse pancreatic acinar cells stimulated with pilocarpine to induce secretion. Our findings suggest that each condensing vacuole/immature granule of pancreatic acinar cells is formed by the progressive aggregation of 106 to 128 "unit progranules" of narrowly fixed volume, define a range of 7.7 to 9.2 for the factor of volume condensation between the largest immature granules and the mature unit granule, and predict that the formation of a single mature unit granule by the aggregation and fusion of unit progranules involves a net reduction of at least 95% in the amount of membrane surface area associated with these structures. PMID- 8001089 TI - Projections of 5-hydroxytryptamine-immunoreactive neurons in guinea-pig distal colon. AB - The presence of 5-hydroxytryptamine in enteric neurons of the guinea-pig distal colon was demonstrated by immunohistochemistry and the projections of the neurons were determined. 5-Hydroxytryptamine-containing nerve cells were observed in the myenteric plexus but no reactive nerve cells were found in submucous ganglia. Varicose reactive nerve fibres were numerous in the ganglia of both the myenteric and submucous plexuses, but were infrequent in the longitudinal muscle, circular muscle, muscularis mucosae and mucosa. Reactivity also occurred in enterochromaffin cells. Lesion studies showed that the axons of myenteric neurons projected anally to provide innervation to the circular muscle and submucosa and to other more anally located myenteric ganglia. The results suggest that a major population of 5-hydroxytryptamine neurons in the colon is descending interneurons, most of which extend for 10 to 15 mm in the myenteric plexus and innervate both 5-hydroxytryptamine and non-5-hydroxytryptamine neurons. PMID- 8001088 TI - The immunolocalization of small nuclear ribonucleoprotein particles in testicular cells during the cycle of the seminiferous epithelium of the adult rat. AB - The objective of this study was to determine the cellular and subcellular distribution of small nuclear ribonucleoprotein particles (snRNPs) in the adult rat testis in relation to the different cell types at the various stages of the cycle of the seminiferous epithelium. The distribution of snRNPs in the nucleus and cytoplasm of germ cells was quantitated in an attempt to correlate RNA processing with morphological and functional changes occurring during the development of these cells. Light-microscopic immunoperoxidase staining of rat testes with polyclonal anti-Sm and monoclonal anti-Y12 antibodies localized spliceosome snRNPs in the nuclei and cytoplasm of germ cells up to step 10 spermatids. Nuclear staining was intense in Sertoli cells, spermatogonia, spermatocytes, and in the early steps of round spermatid development. Although comparatively weaker, cytoplasmic staining for snRNPs was strongest in mid and late pachytene spermatocytes and early round spermatids. Quantitative electron microscopic immunogold labeling of Lowicryl embedded testicular sections confirmed the light-microscopic observations but additionally showed that the snRNP content peaked in the cytoplasm of midpachytene spermatocytes and in the nuclei of late pachytene spermatocytes. The immunogold label tended to aggregate into distinct loci over the nuclear chromatin. The chromatoid body of spermatids and spermatocytes and the finely granular material in the interstices of mitochondrial aggregates of spermatocytes were found to be additional sites of snRNP localization and were intensely labeled. This colocalization suggests that these dense cytoplasmic structures may be functionally related. Anti-U1 snRNP antibodies applied to frozen sections showed the same LM localization pattern as spliceosome snRNPs. Anti-U3 snRNP antibodies applied to frozen sections stained nucleoli of germ cells where pre-rRNA is spliced. PMID- 8001090 TI - Annexins in rat enterocyte and hepatocyte: an immunogold electron-microscope study. AB - In the present study, immunogold labeling of ultrathin sections of rat small intestine and liver has been used to obtain insights into the ultrastructural localization and possible functions of annexins. In enterocytes, annexins II, IV, and VI are found at the periphery of the core of each microvillus and of the rootlets, but are absent from the interrootlet space. Annexins II, IV, and VI are also observed close to the interdigitated plasma membrane. In hepatocytes, only annexin VI is found to be concentrated within the microvilli in the bile canaliculi, on the inner face of the sinusoidal cell surface, particularly in the space of Disse, and all along the plasma membrane. Annexin VI is also detected in mitochondria of enterocytes and hepatocytes. These localizations are in agreement with the concept of a close calcium-dependent association of annexins with membranes and cytoskeletal proteins, particularly with actin. Moreover, they support the hypothesis of an involvement of annexins in exocytotic and endocytotic processes, which take place in epithelial cells. PMID- 8001092 TI - Electron-microscopic investigations of vasoactive intestinal peptide (VIP)-like immunoreactive terminal formations in the lateral septum of the pigeon. AB - Vasoactive intestinal peptide (VIP)-like immunoreactive terminal fields were examined in the lateral septum of the pigeon by means of immunocytochemistry. According to light-microscopic observations, these projections originated from VIP-like immunoreactive cerebrospinal fluid (CSF)-contacting neurons, which are located in the ependymal layer of the lateral septum and form a part of the lateral septal organ. The processes of these cells gave rise to dense terminal like structures in the lateral septum. Pre-embedding immuno-electron microscopy revealed that VIP-like immunoreactive axon terminals had synaptoid contacts with perikarya of small VIP-immunonegative neurons of the lateral septum, which were characterized by an invaginated nucleus, numerous mitochondria, a well-developed Golgi apparatus, endoplasmic reticulum and a small number of dense-core vesicles (about 100 nm in diameter). VIP-like immunoreactive axons were also seen in contact with immunonegative dendrites in the lateral septum. In both axosomatic and axodendritic connections, VIP-like immunoreactive presynaptic terminals contained large dense-core vesicles, clusters of small vesicles and mitochondria. These findings suggest that VIP-immunoreactive neurons of the lateral septal organ project to small, presumably peptidergic nerve cells of the lateral septum and that the VIP-like neuropeptide serves as a neuromodulator (-transmitter) in this area. PMID- 8001091 TI - The neurite growth promoting protease nexin 1 in glial cells of the olfactory bulb of the gerbil: an ultrastructural study. AB - The glia-derived serine protease inhibitor and neurite outgrowth promoter protease nexin-1 (PN-1) is expressed in Schwann cell precursors and astroblasts during embryogenesis. In the adult nervous system, PN-1 persists in the Schwann cells and olfactory glia only. Light-microscopic immunohistochemistry has revealed the presence of PN-1 in the olfactory mucosa and in the nerve fiber layer of the olfactory bulb. The present electron-microscopic study of the gerbil olfactory bulb confirms the occurrence of PN-1 in ensheathing cells of the olfactory nerve fiber layer, a special type of glia which envelopes olfactory axons. In addition, PN-1 is contained in typical astrocytes of the nerve fiber layer and of the glomerular layer. It is inferred that synthesis of PN-1 in the olfactory bulbs is maintained throughout adulthood because its neurite outgrowth promoting action is required for the continuous renewal of olfactory receptor neurons. PMID- 8001094 TI - "Barotrauma's" challengers: observations worth noting. PMID- 8001093 TI - Comparative study of the angiographic morphology of coronary artery lesions treated with PTCA, directional coronary atherectomy, or high-speed rotational ablation. AB - To evaluate trends in morphology-based intervention selection, series of 110 consecutive procedures of each of three devices, percutaneous transluminal balloon coronary angioplasty (PTCA), directional coronary atherectomy (DCA), or high-speed rotational ablation (HSRA), were reviewed. PTCA was used mainly in discrete, concentric, smooth, ACC/AHA type A and B1 lesions. PTCA was used less frequently on a bend, branching points or in calcified lesions. Using PTCA as a reference, DCA was used more often for the treatment of discrete, proximal, eccentric, and noncalcified lesions, often complicated with thrombus and located on straight segments. HSRA was used more frequently in diffuse, calcified multiple complicated and B2+C type lesions with frequent side branches and bend points. These results suggest that directional atherectomy and rotational ablation may be helpful in expanding the capacity of the operator to approach prognostically unfavorable lesions. PMID- 8001095 TI - Comparison of hemodynamic and Doppler echocardiographic effects of a new low osmolar nonionic and a standard ionic contrast agent after left ventriculography. AB - The hemodynamic effects of a new nonionic low osmolar contrast agent (iomeprol) during left ventriculography (LC) was compared with a standard ionic contrast agent (meglumine diatrizoate) in a randomized double blind study in 30 patients with suspected coronary artery disease and normal systolic ventricular function. LV diastolic function was assessed by Doppler echocardiographic recording of the transmittal filling curve and by intraventricular tip-manometry before and within 30 sec of the LC. In the group receiving the ionic contrast agent the systolic pressure fell from 126 +/- 23 to 111 +/- 18 mmHg (P < 0.05), and heart rate increased from 64 +/- 9 to 71 +/- 11 min-1 (P < 0.05), while no such effects were observed with the nonionic contrast agent, indicating differences in the vasodilator properties. The latter caused an increase of the peak early Doppler velocity (52 +/- 11 to 62 +/- 14 cm/sec; P < 0.05). After the ionic contrast agent, the effect on the peak early Doppler velocity was less pronounced, probably due to an interaction with the known depressant effect of the increase in heart rate on the early Doppler velocity. In both groups the left ventricular end diastolic pressure was increased from 7 +/- 3 to 10 +/- 4 mmHg. No significant effects on peak-dp/dt and dp/dt were observed in either group. The nonionic contrast agent iomeprol had no significant effect on systolic arterial pressure and heart rate in contrast to the ionic contrast agent, probably due to a less pronounced vasodilator effect. Despite these differences of the global hemodynamic response, there were similar effects of both contrast agents on LV diastolic filling. PMID- 8001096 TI - Low osmolal contrast: is it a luxury we can no longer afford? PMID- 8001097 TI - Rotational coronary atherectomy with adjunctive balloon angioplasty for the treatment of ostial lesions. AB - Conventional balloon angioplasty (PTCA) of ostial lesions (OL) is associated with suboptimal results and a higher complication rate. Partial plaque ablation with rotational atherectomy (RA) before PTCA might improve results. This approach was used in 63 patients (pts) (mean age 64 +/- 10 yrs; 44 men, 19 women) with 69 OL. There were 15 aorto-OL and 54 branch-OL. Calcification was more frequent in aorto OL than in branch-OL (67% vs. 35%, P < 0.05). Mean burr size was 1.8 +/- 0.3 mm. Burr-artery ratio was 0.74 +/- 0.10. Adjunctive PTCA was systematically performed. Procedural success was achieved in 58 pts (92%): 14 aorto-OL (93%) and 50 branch-OL (93%) were successfully treated; major complications occurred in 1 (7%) aorto-OL and 1 (2%) branch-OL. Uncomplicated failure occurred in three cases. Minimal lumen diameter (MLD) increased from 0.69 +/- 0.31 mm before RA to 1.43 +/- 0.28 mm after RA (P < 0.001) and 2.16 +/- 0.29 mm after PTCA (P < 0.001). Diameter stenosis (DS) decreased from 75 +/- 13% before RA to 32 +/- 12% after RA (P < 0.001) and 14 +/- 10% after PTCA (P < 0.001). All successfully treated pts underwent repeat angiography 24 h later and exercise testing or repeat cardiac catheterization > 6 mo later. At 24 h repeat angiography, DS was 17 +/- 15% (P = NS vs. after PTCA); no lesion had a DS > or = 50%. Follow-up coronary angiography was performed in 30 pts (52%) who had abnormal stress testing: 13 pts (43%) showed angiographic restenosis in at least one successfully treated OL. (ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8001098 TI - Percutaneous mitral commissurotomy for severe mitral stenosis during pregnancy. AB - Percutaneous mitral commissurotomy was performed in 27 pregnant females aged 24.9 +/- 3.14 years (range 20-30 years) with severe mitral stenosis at 22.2 +/- 4.3 weeks (range 18-32 weeks) of gestation. All patients were in New York Heart Association functional class IV at the time of procedure. The procedure was performed using the flow guided Inoue balloon in 25 patients and double balloon technique in 2 patients. Percutaneous mitral commissurotomy was successful in 26 patients. The mitral valve area assessed by Doppler echocardiography (pressure half time) increased from 0.78 +/- 0.19 cm2 (range 0.5-1.0 cm2) to 2.2 +/- 0.12 cm2 (range 1.9-2.6 cm2) (P < 0.001). The mean mitral gradient decreased from 30.5 +/- 7.6 mm Hg (range 22.5-41.4 mm Hg) to 6.1 +/- 2.6 mm Hg (range 4.2-12.3 mm Hg) (P < 0.001). The end diastolic gradient decreased from 28.3 +/- 4.2 mm Hg (range 23-37 mm Hg) to 2.8 +/- 1.5 mm Hg (range 0-5 mm Hg) (P < 0.001). The total fluoroscopy time was 5.6 +/- 2.2 min (range 2.7-8.9 min). Mitral regurgitation increased by one grade in 7 patients. One patient developed severe mitral regurgitation with anterior mitral leaflet tear needing immediate mitral valve replacement. Twenty-six patients improved to New York Heart Association class I after the procedure. Twenty-four patients had full-term, normal delivery and gave birth to healthy infants. The patients were followed up for 1-36 months (mean 16.6 +/- 7.8 months).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8001099 TI - Coronary artery dissection caused by exit of the guidewire through the distal perfusion sidehole of an auto-perfusion angioplasty balloon catheter. AB - A previously unrecognized cause of coronary artery dissection is reported. A 67 year-old woman underwent angioplasty of the right coronary artery using an autoperfusion balloon catheter. Dissection occurred because the balloon catheter was advanced while the guidewire exited from one of the distal perfusion sideholes. PMID- 8001100 TI - Epidural abscess as a complication of coronary angioplasty: a rare but dangerous complication. AB - We report a rare case of lumbosacral epidural abscess as a complication of coronary angioplasty in a 56-year-old male. We outline the mechanism of the abscess and the need for increased awareness and swift management of this entity. PMID- 8001101 TI - Intracoronary stenting in acute myocardial infarction. AB - Stent implantation into an infarct-related artery during acute myocardial infarction is generally contraindicated because of the risk of stent thrombosis. We report on 3 patients who had successful stenting for an acute occlusive dissection that developed during direct infarct coronary angioplasty and was refractory to conventional prolonged balloon dilatation, with good long-term clinical and angiographic results. The prerequisites for success include proper premedication, presence of only a minimal amount of thrombus in the infarct related artery, liberal use of intracoronary thrombolytic therapy, as perfect an angiographic result as possible, as well as careful and aggressive post-stenting anticoagulation. PMID- 8001102 TI - Obstruction of the right pulmonary artery by an aortic aneurysm complicating previous coronary bypass grafting. AB - We report a case of right main pulmonary artery compression due to a type II dissecting aortic aneurysm simulating massive pulmonary artery embolism. Aortic tear and intimal splitting developed around an aortocoronary bypass graft performed 11 months earlier. Ultrasound detected the aortic aneurysm and pulmonary hypertension, and excluded emboli in the pulmonary artery. Pulmonary angiography explained the lung involvement, showing compression of the right main pulmonary artery. Coronary and aortic angiograms demonstrated that the aortic aneurysm developed around the right venous bypass graft. Surgery confirmed the angiographic findings and the pathogenesis of the syndrome. PMID- 8001103 TI - Limitations of translesional pressure and flow velocity for long ostial left anterior descending stenoses. AB - Translesional pressure and flow velocity can be used to assess angiographically intermediate or indeterminate lesions. Ostial narrowings and long lesions represent situations that may require both pressure and flow velocity assessment. In patients with hypertension, diabetes mellitus, and chronic renal failure, distally measured absolute and regional coronary reserve values alone may not be helpful in selecting lesions requiring intervention. PMID- 8001104 TI - Radiological quality of coronary guiding catheters: a quantitative analysis. AB - Quantitative coronary angiography (QCA) is a validated and widely accepted method to investigate changes in arterial dimension over time. Calibration of measurements is enabled by the use of the coronary catheter as a scaling device. The dimensions and laminar composition of coronary catheters, however, have changed significantly over recent years and the suitability of the current generation of coronary catheters for calibration purposes has not been validated. We therefore recorded 57 coronary guiding catheters on cinefilm, and compared their automated quantitative measurements (Cardiovascular Angiography Analysis System, CAAS) with their true values (precision micrometer). We found an overall underestimation of quantitatively derived dimensions, ranging from -8.9 to +4% for water-filled catheters and from -15.5 to -3.9% for contrast-filled catheters. In conclusion, while the current generation of coronary guiding catheters shows a wide variety in radiological quality, it can be clearly detected by the CAAS system, and is suitable for calibration of QCA measurements (with the exception of the DVI atherectomy catheter), provided that calibration is done on contrast empty catheters. PMID- 8001105 TI - CAAS. II: A second generation system for off-line and on-line quantitative coronary angiography. AB - The Cardiovascular Angiography Analysis System (CAAS) has been completely redesigned and transferred to a modern platform. The user-friendly environment together with a number of image processing techniques and tools allow easy and fast analysis of cardiovascular angiographic images. These images are obtained either on-line by means of a frame grabber hooked on the video output of the X ray equipment or off-line by digitising 35-mm cine film frames. In addition, images can be acquired more directly by means of a network link. Images stored on disk in different formats, including MS-DOS, can also be analysed. Accurate and reliable quantitative analysis of coronary stenoses and assessment of their related functional significance may offer the clinician a tool in a stratification of patients at risk. The semireal-time environment will make it possible for the cardiologist to quickly respond to the results of recanalisation procedures while the patient is still in the catheterisation laboratory. The addition of a video front end makes the system available to all clinically relevant X-ray imaging equipment. A detailed comparison with the former CAAS on the basis of analysis of 40 arterial segments in routinely acquired cineangiograms demonstrated no statistically significant differences between the two analysis systems. Repeated analysis of the same segments yielded inter- and intraobserver variabilities for the obstruction diameter of 0.096 and 0.108 mm, respectively. For the computed reference diameter the values are 0.099 and 0.096 mm, respectively, and for the percentage diameter stenosis 4.67 and 5.37%, respectively. PMID- 8001106 TI - Initial experience with the Europass: a new ultra-low profile monorail balloon catheter. AB - One of the causes for percutaneous transluminal coronary angioplasty (PTCA) failure is the inability to cross the lesion with the balloon catheter after guidewire positioning. The Europass coronary angioplasty catheter is a monorail Duralyn balloon catheter developed to enhance lesion crossability and to overcome this limitation. This system was evaluated in 50 patients in which target lesions were chronic total coronary occlusions (12 cases) or stenoses that could not be reached or crossed by other new monorail balloon catheters. Overall procedural success was obtained in 49/50 patients (98%), using a single Europass balloon catheter in 46/50 patients (92%), with no in-hospital complications. Its low profile, small distal shaft, and excellent trackability allowed successful angioplasty in cases where other catheters failed. This balloon catheter represents a significant advance in angioplasty technology and can be considered as a first-choice device for a safe and expeditious single-operator procedure. PMID- 8001107 TI - Prolonged intracoronary infusion of streptokinase: an alternative pharmacologic approach to extensive thrombus in native coronary artery. AB - Several reports suggest that pretreatment of intracoronary thrombus with fibrinolytic agents may reduce the risk for complications during subsequent balloon angioplasty. We report a case, for the first time, of successful lysis of an extensive thrombus in a native coronary artery by administering a prolonged intracoronary infusion of streptokinase to facilitate subsequent angioplasty and discuss the management strategy when intracoronary thrombus is encountered. PMID- 8001108 TI - Use of cutoff pigtail catheters with intraluminal guidewires in interventional procedures in congenital heart disease. AB - Advances in interventional cardiac catheterization have necessitated technique modifications to ensure patient safety while allowing data acquisition. The use of cutoff pigtail catheters over guidewires for pressure recordings and angiography exemplifies such a modification. The primary purpose of this study was to ascertain contrast volume and flow rates achievable using such a system. A total of 140 used catheters of various sizes, with intraluminal guidewires (0.035 inch in 6, 7, and 8F; 0.025 inch in 5F) were subjected to contrast injections at increasing rates and volumes until rupture occurred. The 7F catheters allowed volume delivery at 15-40 ml at 15 ml/sec, 8F catheters 40 ml at 30 ml/sec, and 5 and 6F catheters 10 ml at 10 ml/sec. All ruptured within 3 cm of the hub, at < or = 900 PSI. A review of 737 clinical procedures revealed adequate pressure recordings and angiographic details in all, uncomplicated save for one intracardiac wire dislodgement. PMID- 8001109 TI - Quantification of intracoronary volume by videodensitometry: validation study using fluid filling of human coronary casts. AB - Changes in intracoronary volume reflect the hemodynamic significance of progression or regression of diffuse coronary artery disease where intracoronary catheters cannot be applied for direct measurements due to small vessel dimensions. We have validated the videodensitometric measurement of intracoronary volume with epoxy casts of postmortem human coronary arteries. The volume of 31 coronary segments (cross-sectional areas in a range of 2-13 mm2) measured by fluid-filling using a precision dispenser was compared with the respective single plane intracoronary volume assessments obtained by the videodensitometric algorithm of the new generation Cardiovascular Angiography Analysis System (CAAS II). The true and measured values of volume were compared by calculation of the mean of the signed differences +/- standard deviation and by linear regression analysis. Videodensitometric measurement of intracoronary volume correlate well with fluid-filling of human coronary artery casts (correlation coefficient: r = 0.99, y = 1.96 +/- 0.99x, standard error of estimate: SEE = 3.96) with a significant trend towards overestimation of true volume values (mean difference = 1.73 +/- 3.64 mm3, P < 0.05). Intracoronary volume estimations can be used to measure changes of luminal dimensions of coronary arteries and may offer a new approach to assessment of progression or regression of diffuse coronary artery disease. PMID- 8001110 TI - Right coronary angulated views. PMID- 8001111 TI - Issues of QCA validation. PMID- 8001112 TI - Promoter structure, promoter recognition, and transcription activation in prokaryotes. PMID- 8001113 TI - Protein-protein interaction converts a proton pump into a sensory receptor. PMID- 8001114 TI - Transcriptional control points during lymphopoiesis. PMID- 8001115 TI - Behavioral and anatomical deficits in mice homozygous for a modified beta-amyloid precursor protein gene. AB - The beta-amyloid precursor protein (beta APP) gene of the mouse was disrupted by inserting into exon 2 a cassette containing a neomycin resistance gene and a putative transcription termination sequence. Contrary to expectation, brain and other tissues from mice homozygous for the insertion still contained beta APP specific RNA, albeit at a level 5- to 10-fold lower than wild type and lacking the disrupted exon, which had been spliced out. The brain contained shortened beta APP-specific protein at a low level. Mutant mice were severely impaired in spatial learning and exploratory behavior and showed increased incidence of agenesis of the corpus callosum. PMID- 8001116 TI - Isolation of a protein that is essential for the first step of nuclear protein import. AB - We have purified a cytosolic protein from Xenopus eggs that is essential for selective protein import into the cell nucleus. The purified protein, named importin, promotes signal-dependent binding of karyophilic proteins to the nuclear envelope. We have cloned, sequenced, and expressed a corresponding cDNA. Importin shows 44% sequence identity with SRP1p, a protein associated with the yeast nuclear pore complex. Complete, signal-dependent import into HeLa nuclei can be reconstituted by combining importin purified from Xenopus eggs or expressed in E. coli with Ran/TC4. Evidence for additional stimulatory factors is provided. PMID- 8001117 TI - Xenopus chordin: a novel dorsalizing factor activated by organizer-specific homeobox genes. AB - A Xenopus gene whose expression can be activated by the organizer-specific homeobox genes goosecoid and Xnot2 was isolated by differential screening. The chordin gene encodes a novel protein of 941 amino acids that has a signal sequence and four Cys-rich domains. The expression of chordin starts in Spemann's organizer subsequent to that of goosecoid, and its induction by activin requires de novo protein synthesis. Microinjection of chordin mRNA induces twinned axes and can completely rescue axial development in ventralized embryos. This molecule is a potent dorsalizing factor that is expressed at the right time and in the right place to regulate cell-cell interactions in the organizing centers of head, trunk, and tail development. PMID- 8001119 TI - Transcriptional activation by p53 correlates with suppression of growth but not transformation. AB - The tumor suppressor protein p53 shows growth and transformation suppression functions that are frequently lost by mutant proteins detected in cancers. Using a large series of p53 mutants, we have demonstrated an excellent correlation between transcriptional activation and growth suppression in p53-null human cells. Not all transcriptionally active mutants retain the ability to suppress transformation in primary rodent cells, however, and two tumor-derived point mutants displayed some evidence of both transforming and transactivating activity. Transformation by these mutants was not mediated by transdominant repression of endogenous p53 transactivating function, and cell lines expressing these p53 proteins showed elevated p53 transcriptional activity. Our results suggest that activation of transcriptional regulation by p53 will not necessarily result in tumor suppression. PMID- 8001118 TI - Groucho is required for Drosophila neurogenesis, segmentation, and sex determination and interacts directly with hairy-related bHLH proteins. AB - We have used the interaction trap, a yeast two-hybrid system, to identify proteins interacting with hairy, a basic-helix-loop-helix (bHLH) protein that represses transcription during Drosophila embryonic segmentation. We find that the groucho (gro) protein binds specifically to hairy and also to hairy-related bHLH proteins encoded by deadpan and the Enhancer of split complex. The C terminal WRPW motif present in all these bHLH proteins is essential for this interaction. We demonstrate that these associations reflect in vivo maternal requirements for gro during neurogenesis, segmentation, and sex determination, three processes regulated by the above bHLH proteins, and we propose that gro is a transcriptional corepressor recruited to specific target promoters by hairy related bHLH proteins. PMID- 8001120 TI - Incomplete arrest in the outer membrane sorts NADH-cytochrome b5 reductase to two different submitochondrial compartments. AB - The S. cerevisiae gene MCR1 encodes two mitochondrial isoforms of NADH-cytochrome b5 reductase. The primary translation product has an amino-terminal matrix targeting signal, followed by a stretch of 21 uncharged amino acids. This precursor protein is inserted into the outer membrane, but only about one-third of the molecules become firmly anchored to the outer face of that membrane. The remaining molecules pass through the outer membrane into the inner membrane, are cleaved by inner membrane protease 1, and are released into the intermembrane space. Incomplete translocation arrest in the outer membrane is a novel mechanism by which the product of a single gene is sorted into different compartments of the same organelle. PMID- 8001121 TI - Site-specific conformational alteration of the Oct-1 POU domain-DNA complex as the basis for differential recognition by Vmw65 (VP16). AB - We show that the presence of a regulatory cis-acting element that flanks the core octamer site and dictates selectivity in the response to Vmw65 (VP16), while dispensable for POU binding per se, induces a conformational alteration in the nature of the POU domain in the DNA complex. A single substitution in the flanking signal distorts the POU complex and without affecting overall POU binding prevents Vmw65 interaction. Alternatively, substitution of a residue in the homeodomain predicted to contact the GARAT region prevents its recognition even on a wild-type motif, causing a reversion to the DNA binding pattern seen on a cellular motif and at the same time inefficient recognition by Vmw65. The results indicate that Vmw65 recognizes a particular POU domain conformation induced by the presence of the flanking GARAT region. PMID- 8001122 TI - Genetic recombination in E. coli: RuvC protein cleaves Holliday junctions at resolution hotspots in vitro. AB - The E. coli RuvC protein resolves Holliday junctions during genetic recombination and postreplication repair. Using recombination intermediates made by RecA protein, we have identified specific "hotspots" for RuvC resolution. Characterization of these sites reveals a common tetranucleotide sequence, with the consensus 5'-A/TTT decreases G/C-3'. The correct orientation of the resolution site is required for cleavage. These observations suggest that the strand bias of this sequence will affect the outcome of recombinational crosses by directing resolution to either "patch" or "splice" recombinant products. Mutation of the consensus site in synthetic Holliday junctions abolishes or significantly reduces the efficiency of cleavage, although binding is unaffected, demonstrating that junction recognition and incision are biochemically separable events. We propose that efficient RuvC resolution requires the translocation of Holliday junctions to specific cleavage sites, thus providing a biochemical basis for the similar genetic defects observed in ruvA, ruvB, and ruvC mutants. PMID- 8001123 TI - A novel epigenetic effect can alter centromere function in fission yeast. AB - A novel epigenetic mechanism that can affect minichromosome centromere function in vivo has been identified in S. pombe. This epigenetic system can result in the conversion of a nonfunctional centromere to a functional one without changes in the content, structural arrangement, or chemical modification state of the minichromosomal DNA. The conversion from a centromere-inactive to an active state, which is evident with minichromosomes carrying abbreviated centromeric DNA constructions, occurs with a relatively high frequency during mitotic cell divisions and readily provides an in vivo assay for proper centromere formation. The centromere-targeted epigenetic system supports a model for centromere function that involves specific de novo folding of centromeric components into a higher order chromatin structure. PMID- 8001124 TI - The helix-loop-helix gene E2A is required for B cell formation. AB - Heterodimers between tissue-specific basic-helix-loop-helix proteins and the gene products of E2A play major roles in determining tissue-specific cell fate. To understand the broad role of E2A in development, we have generated E2A mutant mice following homologous recombination in embryonic stem cells. Homozygous mutant mice develop to full term without apparent abnormalities, but then display a high rate of postnatal death. The surviving mice show retarded postnatal growth. Detailed examination of hematopoiesis reveals that the homozygous mutant mice contain no B cells while other lineages including T cell, granulocyte, macrophage, and erythroid are intact. The block to B cell differentiation occurs prior to immunoglobulin gene DH-JH rearrangement and the expression of the B lineage-specific marker B220. Surprisingly, heterozygous embryos contain, on average, about half as many B cells as wild-type embryos, suggesting the existence of a counting mechanism that translates levels of E2A into numbers of B cells. PMID- 8001125 TI - E2A proteins are required for proper B cell development and initiation of immunoglobulin gene rearrangements. AB - E12 and E47 are two helix-loop-helix transcription factors that arise by alternative splicing of the E2A gene. Both have been implicated in the regulation of immunoglobulin gene expression. We have now generated E2A (-/-) mice by gene targeting. E2A-null mutant mice fail to generate mature B cells. The arrest of B cell development occurs at an early stage, since no immunoglobulin DJ rearrangements can be detected in homozygous mutant mice. While immunoglobulin germline I mu RAG-1, mb-1, CD19, and lambda 5 transcripts are dramatically reduced in fetal livers of E2A (-/-) mice, B29 and mu degrees transcripts are present, but at lower levels. In addition, we show that Pax-5 transcripts are significantly reduced in fetal livers of E2A (-/-) mice. These data suggest a crucial role for E2A products as central regulators in early B cell differentiation. PMID- 8001126 TI - Constitutive expression of the Id1 gene impairs mouse B cell development. AB - The Id proteins are inhibitors of the basic-helix-loop-helix (bHLH) transcription factors. In the B cell lineage, the Id1 and Id2 genes are expressed in pro-B cells and down-regulated during differentiation. To determine the role of bHLH proteins and the significance of down-regulation of Id genes in B cell development, transgenic mice constitutively expressing the Id1 gene were generated. Their phenotype suggests that B cell development is impaired at an early stage. Primarily, these mice have few B220+ IgM+ mature B or B220+ CD43- pre-B cells in the bone marrow, reduced frequencies of V(D)J and V kappa J kappa recombination of the immunoglobulin loci, and lower expression levels of the immunoglobulin, RAG-1, RAG-2, and lambda 5 genes. PMID- 8001127 TI - Complete block of early B cell differentiation and altered patterning of the posterior midbrain in mice lacking Pax5/BSAP. AB - The Pax5 gene, coding for the transcription factor BSAP, was mutated in the mouse germline by targeted disruption. Homozygous mutant mice were born alive, became growth retarded, and usually died within three weeks. About 5% of mutants survived to adulthood and were fertile, but severely runted. Morphogenesis of the posterior midbrain was affected as early as embryonic day 16.5, leading to a reduction of the inferior colliculus near the midline and to altered foliation of the anterior cerebellum. Moreover, all mutants failed to produce small pre-B, B, and plasma cells owing to a complete arrest of B cell development at an early precursor stage. These data define a key role for Pax5 in early B lymphopoiesis and midbrain patterning. PMID- 8001128 TI - Partial T cell signaling: altered phospho-zeta and lack of zap70 recruitment in APL-induced T cell anergy. AB - Studies of T cell responses to altered peptide ligands (APLs) have provided functional evidence that a T cell receptor (TCR) can interpret subtle changes in its ligand, resulting in different phenotypic outcomes. One dramatic effect of APL stimulation with live antigen-presenting cells (APCs) is the induction of energy as opposed to proliferation. We investigated the intracellular signaling events involved in generating this unresponsiveness by comparing protein-tyrosine phosphorylation patterns after stimulation with anergy-inducing APL or the immunogenic peptide. In resting T cell clones, presentation with APL/live APC stimulated a unique pattern of TCR phospho-zeta species and a subsequent lack of association with zap70. This demonstrates that the TCR-CD3 complex can engage selective intracellular biochemical signaling pathways as a direct consequence of the nature of the ligand recognized and the initial phosphotyrosine pattern of the TCR-CD3 proteins, leading to different phenotypes. PMID- 8001129 TI - Isolation of a novel gene mutated in Wiskott-Aldrich syndrome. PMID- 8001130 TI - The mouse segmentation gene kr encodes a novel basic domain-leucine zipper transcription factor. AB - The mouse kreisler (kr) mutation causes segmentation abnormalities in the caudal hindbrain and defective inner ear development. Based on an inversion discovered in the original kr allele, we selected a candidate cDNA highly expressed in the developing caudal hindbrain. This cDNA encodes a basic domain-leucine zipper (bZIP) transcription factor and was confirmed to represent the kr gene by analysis of a second kr allele, generated by chemical mutagenesis, in which a serine is substituted for an asparagine residue conserved in the DNA-binding domain of all known bZIP family members. The identity, expression, and mutant phenotype of kr indicate an early role in axial patterning and provide insights into the molecular and embryologic mechanisms that govern hindbrain and otic development. PMID- 8001131 TI - Light inactivation of Arabidopsis photomorphogenic repressor COP1 involves a cell specific regulation of its nucleocytoplasmic partitioning. AB - Arabidopsis COP1 acts as a repressor of photomorphogenesis in darkness, and light stimuli abrogate this suppressive action. COP1, when fused to beta-glucuronidase (GUS), is enriched in the nucleus in darkness, but not in the light, in hypocotyl cells of Arabidopsis seedlings and epidermal cells of onion bulbs. In Arabidopsis hypocotyl cells, the nuclear GUS-COP1 level changes in response to dark-light transitions and quantitatively correlates with the extent of repression of photomorphogenic development. In root cells, GUS-COP1 is constitutively nuclear, consistent with an established role of COP1 in suppressing root chloroplast development in both light and darkness. We conclude that COP1 acts inside the nucleus to suppress photomorphogenesis and that light inactivation of COP1 involves a cell type-specific control of its nucleocytoplasmic partitioning. PMID- 8001132 TI - Multiple protein-aspartate phosphatases provide a mechanism for the integration of diverse signals in the control of development in B. subtilis. AB - The initiation of sporulation in B. subtilis is regulated by the Spo0A transcription factor, which is activated by phosphorylation to control developmental switching from the vegetative to the sporulation state. The level of phosphorylation of Spo0A is regulated by the phosphorelay, a signal transduction system based on the protein-histidine kinase-response regulator two component paradigm. To initiate sporulation, the cell must recognize and interpret a large variety of environmental, metabolic, and cell cycle signals that influence the phosphorylation level of Spo0A. We describe here a family of protein-aspartate phosphatases with activity on Spo0F approximately P, a response regulator component of the phosphorelay, that provide a mechanism for signal recognition and interpretation. These phosphatases function to drain the phosphorelay, lower Spo0A approximately P levels, and prevent sporulation. The integration of diverse environmental signals that affect the initiation of sporulation likely occurs through the competition between opposing activities of protein kinases and protein phosphatases. PMID- 8001133 TI - An intermolecular disulfide bond stabilizes E2A homodimers and is required for DNA binding at physiological temperatures. AB - It is demonstrated in this report that purified E2A helix-loop-helix (HLH) proteins spontaneously form homodimers that are linked by an intermolecular disulfide bond. These homodimers bind DNA at physiological temperatures but fail to associate with either Id or MyoD. When the disulfide bond is reduced by an activity present in muscle cell lysates or disrupted by site-directed mutagenesis, the monomeric form of the protein is strongly favored at 37 degrees C. These E2A monomers cannot bind DNA but heterodimerize efficiently with Id and MyoD. It is also shown that an intermolecular disulfide bond cross-links E2A homodimers in B cells but not in muscle cells in which only heterodimers have been detected. These results suggest a novel mechanism for regulating the dimerization status and DNA binding properties of E2A HLH transcription factors. PMID- 8001134 TI - Mutation of a meiosis-specific MutS homolog decreases crossing over but not mismatch correction. AB - MSH4 is a novel meiosis-specific gene required for wild-type levels of spore viability in S. cerevisiae. The predicted product of the MSH4 gene is homologous to the MutS family of proteins; however, msh4-null mutants have no apparent defect in mismatch repair. msh4 mutant strains display wild-type levels of gene conversion and postmeiotic segregation, but they show a reduction in crossing over and a resultant increase in nondisjunction of homologous chromosomes at meiosis I. Immunofluorescence experiments demonstrate that the Msh4 protein is localized to discrete sites on pachytene chromosomes. We propose that Msh4 interacts with a recombination intermediate to influence its resolution. PMID- 8001135 TI - The MO15 cell cycle kinase is associated with the TFIIH transcription-DNA repair factor. AB - A protein kinase activity that phosphorylates the C-terminal domain (CTD) of RNA polymerase II and is associated with the basal transcription-repair factor TFIIH (also called BTF2) resides with MO15, a cyclin-dependent protein kinase that was first found to be involved in cell cycle regulation. Using in vivo and in vitro repair assays, we show that MO15 is important for nucleotide excision repair, most likely through its association with TFIIH, thus providing an unexpected link among three important cellular mechanisms. PMID- 8001136 TI - Relationship of CDK-activating kinase and RNA polymerase II CTD kinase TFIIH/TFIIK. AB - KIN28, a member of the p34cdc2/CDC28 family of protein kinases, is identified as a subunit of yeast RNA polymerase transcription factor IIH (TFIIH) on the basis of sequence determination, immunological reactivity, and copurification. KIN28 is, moreover, one of three subunits of TFIIK, a subassembly of TFIIH with protein kinase activity directed toward the C-terminal repeat domain (CTD) of the largest subunit of RNA polymerase II. Itself a phosphoprotein, KIN28 interacts specifically with the two largest subunits of RNA polymerase II. Previous work of others points to two further associations: KIN28 interacts in vivo with the cyclin CCL1, and KIN28 and CCL1 are homologous to human MO15 and cyclin H, which form the cyclin-dependent kinase-activating kinase (CAK). We show that human CAK possesses the CTD kinase activity characteristic of TFIIH. PMID- 8001137 TI - Autosomal sex reversal and campomelic dysplasia are caused by mutations in and around the SRY-related gene SOX9. AB - A human autosomal XY sex reversal locus, SRA1, associated with the skeletal malformation syndrome campomelic dysplasia (CMPD1), has been placed at distal 17q. The SOX9 gene, a positional candidate from the chromosomal location and expression pattern reported for mouse Sox9, was isolated and characterized. SOX9 encodes a putative transcription factor structurally related to the testis determining factor SRY and is expressed in many adult tissues, and in fetal testis and skeletal tissue. Inactivating mutations on one SOX9 allele identified in nontranslocation CMPD1-SRA1 cases point to haploinsufficiency for SOX9 as the cause for both campomelic dysplasia and autosomal XY sex reversal. The 17q breakpoints in three CMPD1 translocation cases map 50 kb or more from SOX9. PMID- 8001138 TI - Adenovirus E1B 19 kDa and Bcl-2 proteins interact with a common set of cellular proteins. PMID- 8001139 TI - Hard target: understanding dopaminergic neurotransmission. PMID- 8001140 TI - Oncogenes and the strategy of growth factors. PMID- 8001141 TI - Cytosolic factors in nuclear transport: what's importin? PMID- 8001142 TI - On neuronal specificity and the molecular basis of perception. PMID- 8001143 TI - Elimination of cocaine-induced hyperactivity and dopamine-mediated neurophysiological effects in dopamine D1 receptor mutant mice. AB - The brain mesoaccumbens dopamine system is intricately involved in the psychomotor stimulant activities of cocaine. However, the extent to which different dopamine receptors mediate these effects has not yet been firmly established. The present study used dopamine D1 receptor mutant mice produced by gene targeting to investigate the role of this receptor in the effects induced by cocaine. In contrast with wild-type mice, which showed a dose-dependent increase in locomotion, D1 mutant mice exhibited a dose-dependent decrease. Electrophysiological studies of dopamine-sensitive nucleus accumbens neurons demonstrated a marked reduction in the inhibitory effects of cocaine on the generation of action potentials. In addition, the inhibitory effects of dopamine as well as D1 and D2 agonists were almost completely abolished, whereas those of serotonin were unaffected. D2-like dopamine receptor binding was also normal. These results demonstrate the essential role of the D1 receptor in the locomotor stimulant effects of cocaine and in dopamine-mediated neurophysiological effects within the nucleus accumbens. PMID- 8001144 TI - The C. elegans gene odr-7 encodes an olfactory-specific member of the nuclear receptor superfamily. AB - Olfactory discrimination is achieved through the action of olfactory neurons with diverse chemical specificities. In C. elegans, at least ten different types of chemosensory neurons respond to different chemicals. The odr-7 gene is required for the function of one pair of chemosensory neurons called AWA neurons. odr-7 null mutants fail to respond to all odorants detected by the AWA neurons, while a missense mutation in odr-7 causes a specific defect in one odorant response. odr 7 encodes a protein with similarity to the DNA-binding domain of the nuclear receptor genes; it is expressed predominantly in the AWA neurons. odr-7 may regulate the expression of olfactory signaling molecules that define a single type of olfactory neuron. PMID- 8001146 TI - Sonic hedgehog and Fgf-4 act through a signaling cascade and feedback loop to integrate growth and patterning of the developing limb bud. AB - Proper limb growth and patterning requires signals from the zone of polarizing activity in the posterior mesoderm and from the overlying apical ectodermal ridge (AER). Sonic hedgehog and Fgf-4, respectively, have recently been identified as candidates for these signals. We have dissected the roles of these secreted proteins in early limb development by ectopically regulating their activities in a number of surgical contexts. Our results indicate that Sonic hedgehog initiates expression of secondary signaling molecules, including Bmp-2 in the mesoderm and Fgf-4 in the ectoderm. The mesoderm requires ectodermally derived competence factors, which include Fgf-4, to activate target gene expression in response to Sonic hedgehog. The expression of Sonic hedgehog and Fgf-4 is coordinately regulated by a positive feedback loop operating between the posterior mesoderm and the overlying AER. Taken together, these data provide a basis for understanding the integration of growth and patterning in the developing limb. PMID- 8001145 TI - Topographic organization of sensory projections to the olfactory bulb. AB - The detection of odorant receptor mRNAs within the axon terminals of sensory neurons has permitted us to ask whether neurons expressing a given receptor project their axons to common glomeruli within the olfactory bulb. In situ hybridization with five different receptor probes demonstrates that axons from neurons expressing a given receptor converge on one, or at most, a few glomeruli within the olfactory bulb. Moreover, the position of specific glomeruli is bilaterally symmetric and is constant in different individuals within a species. These data support a model in which exposure to a given odorant may result in the stimulation of a spatially restricted set of glomeruli, such that the individual odorants would be associated with specific topographic patterns of activity within the olfactory bulb. PMID- 8001147 TI - Intimations of a creature. PMID- 8001148 TI - About turn for the COPs? PMID- 8001149 TI - Protein folding and the regulation of signaling pathways. AB - A growing number of intracellular signaling molecules are found associated with components of the cellular protein folding machinery. In this minireview we suggest that the same ancient cellular process that promotes the folding and assembly of nascent proteins plays a pivotal role in signal transduction by promoting the regulated folding or assembly and disassembly of mature signaling molecules between active and inactive states. Members of the protein folding machinery mediate the activity of various kinases, receptors, and transcription factors. These may be poised in late stages of folding or assembly until upstream signaling events trigger their biogenesis into activated molecules. PMID- 8001150 TI - Shaker K+ channel beta subunits belong to an NAD(P)H-dependent oxidoreductase superfamily. PMID- 8001151 TI - Stimulation of adipogenesis in fibroblasts by PPAR gamma 2, a lipid-activated transcription factor. AB - Peroxisome proliferator-activated receptor gamma 2 (PPAR gamma 2) is an adipocyte specific nuclear hormone receptor that has recently been identified as a key regulator of two fat cell enhancers. Transcriptional activation by PPAR gamma 2 is potentiated by a variety of lipids and lipid-like compounds, including naturally occurring polyunsaturated fatty acids. We demonstrate here that retroviral expression of PPAR gamma 2 stimulates adipose differentiation of cultured fibroblasts. PPAR activators promote the differentiation of PPAR gamma 2 expressing cells in a dose-dependent manner. C/EBP alpha, a second transcription factor induced during adipocyte differentiation, can cooperate with PPAR gamma 2 to stimulate the adipocyte program dramatically. Our results suggest that the physiologic role of PPAR gamma 2 is to regulate development of the adipose lineage in response to endogenous lipid activators and that this factor may serve to link the process of adipocyte differentiation to systemic lipid metabolism. PMID- 8001152 TI - Ectopic expression of Sonic hedgehog alters dorsal-ventral patterning of somites. AB - Differentiation of somites into sclerotome, dermatome, and myotome is controlled by a complex set of inductive interactions. The ability of axial midline tissues, the notochord and floor plate, to induce sclerotome has been well documented and has led to models in which ventral somite identity is specified by signals derived from the notochord and floor plate. Herein, we provide evidence that Sonic hedgehog, a vertebrate homolog of the Drosophila segment polarity gene hedgehog, is a signal produced by the notochord and floor plate that directs ventral somite differentiation. Sonic hedgehog is expressed in ventral midline tissues at critical times during somite specification and has the ability, when ectopically expressed, to enhance the formation of sclerotome and antagonize the development of dermatome. PMID- 8001153 TI - Patterning of mammalian somites by surface ectoderm and notochord: evidence for sclerotome induction by a hedgehog homolog. AB - An early step in the development of vertebrae, ribs, muscle, and dermis is the differentiation of the somitic mesoderm into dermomyotome dorsally and sclerotome ventrally. To analyze this process, we have developed an in vitro assay for somitic mesoderm differentiation. We show that sclerotomal markers can be induced by a diffusible factor secreted by notochord and floor plate and that heterologous cells expressing Sonic hedgehog (shh/vhh-1) mimic this effect. In contrast, expression of dermomyotomal markers can be caused by a contact dependent signal from surface ectoderm and a diffusible signal from dorsal neural tube. Our results extend previous studies by suggesting that dorsoventral patterning of somites involves the coordinate action of multiple dorsalizing and ventralizing signals and that a diffusible form of Shh/Vhh-1 mediates sclerotome induction. PMID- 8001154 TI - Reciprocal changes in expression of the receptor lin-12 and its ligand lag-2 prior to commitment in a C. elegans cell fate decision. AB - During development of the C. elegans hermaphrodite gonad, two cells interact with each other, so that one chooses to become the anchor cell (AC) and the other becomes a ventral uterine precursor cell (VU). This interaction is mediated by the receptor LIN-12 and its apparent ligand LAG-2. We show that initially lin-12 and lag-2 are expressed in both cells, but prior to commitment, the expression patterns change in a reciprocal manner, so that lin-12 expression becomes restricted to the presumptive VU and lag-2 expression becomes restricted to the presumptive AC. In addition, lin-12 activity promotes expression of lin-12 and represses expression of lag-2. Furthermore, we show that positive autoregulation of lin-12 transcription in the presumptive VU is mediated by a cis-acting 5' regulatory sequence and is necessary to specify the VU fate. Our results suggest that transcriptional control is a component of the feedback mechanism involved in specifying the AC and VU fates. PMID- 8001155 TI - Coatomer is essential for retrieval of dilysine-tagged proteins to the endoplasmic reticulum. AB - Dilysine motifs in cytoplasmic domains of transmembrane proteins are signals for their continuous retrieval from the Golgi back to the endoplasmic reticulum (ER). We describe a system to assess retrieval to the ER in yeast cells making use of a dilysine-tagged Ste2 protein. Whereas retrieval was unaffected in most sec mutants tested (sec7, sec12, sec13, sec16, sec17, sec18, sec19, sec22, and sec23), a defect in retrieval was observed in previously characterized coatomer mutants (sec21-1, sec27-1), as well as in newly isolated retrieval mutants (sec21 2, ret1-1). RET1 was cloned by complementation and found to encode the alpha subunit of coatomer. While temperature-sensitive for growth, the newly isolated coatomer mutants exhibited a very modest defect in secretion at the nonpermissive temperature. Coatomer from beta'-COP (sec27-1) and alpha-COP (ret1-1) mutants, but not from gamma-COP (sec21) mutants, had lost the ability to bind dilysine motifs in vitro. Together, these results suggest that coatomer plays an essential role in retrograde Golgi-to-ER transport and retrieval of dilysine-tagged proteins back to the ER. PMID- 8001156 TI - Staufen protein associates with the 3'UTR of bicoid mRNA to form particles that move in a microtubule-dependent manner. AB - Staufen protein is required in order to anchor bicoid (bcd) mRNA at the anterior pole of the Drosophila egg. Here we show that staufen protein colocalizes with bcd mRNA at the anterior, and that this localization depends upon its association with the mRNA. Upon injection into the embryo, bcd transcripts specifically interact with staufen, and we have mapped the sequences required to three regions of the 3'UTR, each of which is predicted to form a long stem-loop. The resulting staufen-bcd 3'UTR complexes form particles that show a microtubule-dependent localization. Since staufen is also transported with oskar (osk) mRNA during oogenesis, staufen associates specifically with both osk and bcd mRNAs to mediate their localizations, but at two distinct stages of development. PMID- 8001157 TI - Crystal structure of the eukaryotic DNA polymerase processivity factor PCNA. AB - The crystal structure of the processivity factor required by eukaryotic DNA polymerase delta, proliferating cell nuclear antigen (PCNA) from S. cerevisiae, has been determined at 2.3 A resolution. Three PCNA molecules, each containing two topologically identical domains, are tightly associated to form a closed ring. The dimensions and electrostatic properties of the ring suggest that PCNA encircles duplex DNA, providing a DNA-bound platform for the attachment of the polymerase. The trimeric PCNA ring is strikingly similar to the dimeric ring formed by the beta subunit (processivity factor) of E. coli DNA polymerase III holoenzyme, with which it shares no significant sequence identity. This structural correspondence further substantiates the mechanistic connection between eukaryotic and prokaryotic DNA replication that has been suggested on biochemical grounds. PMID- 8001158 TI - A missense mutation of the endothelin-B receptor gene in multigenic Hirschsprung's disease. AB - Hirschsprung's disease (HSCR) is characterized by an absence of enteric ganglia in the distal colon and a failure of innervation in the gastrointestinal tract. We recently mapped a recessive susceptibility locus (HSCR2) to human chromosome 13q22, which we now demonstrate to be the endothelin-B receptor gene (EDNRB). We identified in HSCR patients a G-->T missense mutation in EDNRB exon 4 that substitutes the highly conserved Trp-276 residue in the fifth transmembrane helix of the G protein-coupled receptor with a Cys residue (W276C). The mutant W276C receptor exhibited a partial impairment of ligand-induced Ca2+ transient levels in transfected cells. The mutation is dosage sensitive, in that W276C homozygotes and heterozygotes have a 74% and a 21% risk, respectively, of developing HSCR. Genotype analysis of patients in a Mennonite pedigree shows HSCR to be a multigenic disorder. PMID- 8001160 TI - Interaction of endothelin-3 with endothelin-B receptor is essential for development of epidermal melanocytes and enteric neurons. AB - Defects in the gene encoding the endothelin-B receptor produce aganglionic megacolon and pigmentary disorders in mice and humans. We report that a targeted disruption of the mouse endothelin-3 ligand (EDN3) gene produces a similar recessive phenotype of megacolon and coat color spotting. A natural recessive mutation that results in the same developmental defects in mice, lethal spotting (ls), failed to complement the targeted EDN3 allele. The ls mice carry a point mutation of the EDN3 gene, which replaces the Arg residue at the C-terminus of the inactive intermediate big EDN3 with a Trp residue. This mutation prevents the proteolytic activation of big EDN3 by ECE-1. These findings indicate that interaction of EDN3 with the endothelin-B receptor is essential in the development of neural crest-derived cell lineages. We postulate that defects in the human EDN3 gene may cause Hirschsprung's disease. PMID- 8001159 TI - Targeted and natural (piebald-lethal) mutations of endothelin-B receptor gene produce megacolon associated with spotted coat color in mice. AB - Endothelins act on two subtypes of G protein-coupled receptors, termed endothelin A and endothelin-B receptors. We report a targeted disruption of the mouse endothelin-B receptor (EDNRB) gene that results in aganglionic megacolon associated with coat color spotting, resembling a hereditary syndrome of mice, humans, and other mammalian species. Piebald-lethal (sl) mice exhibit a recessive phenotype identical to that of the EDNRB knockout mice. In crossbreeding studies, the two mutations show no complementation. Southern blotting revealed a deletion encompassing the entire EDNRB gene in the sl chromosome. A milder allele, piebald (s), which produces coat color spotting only, expresses low levels of structurally intact EDNRB mRNA and protein. These findings indicate an essential role for EDNRB in the development of two neural crest-derived cell lineages, myenteric ganglion neurons and epidermal melanocytes. We postulate that defects in the human EDNRB gene cause a hereditary form of Hirschsprung's disease that has recently been mapped to human chromosome 13, in which EDNRB is located. PMID- 8001161 TI - Heat shock changes the response of the pso3 mutant of Saccharomyces cerevisiae to 8-methoxypsoralen photoaddition. AB - A putative tolerance, induced by heat shock (HS), to the lethal and mutagenic effects of 8-methoxypsoralen (8-MOP) photoaddition and hyperthermia was analyzed in Saccharomyces cerevisiae using the wild-type strain N123 and the isogenic DNA repair-deficient mutant pso3-1. In wild-type cells, the HS (38 degrees C for 1 h) did not modify either the survival or the mutation frequency observed after 8-MOP photoaddition, even though it conferred protection against the lethal effect of hyperthermia (50 degrees C). In the pso3-1 mutant, HS induced an increase of the survival, and a decrease of the mutation frequency, after 8-MOP photoaddition and it also protected against the lethal effect of hyperthermia. The responses induced by HS were specific for 8-MOP photoaddition, since they were not observed after 254 nm ultraviolet-light damage. These results indicate that the protection conferred by HS depends of the type of lesion, and operates through the induction of different repair processes. In the pso3-1 mutant, HS could channel the repair intermediates to and error-free repair pathway. PMID- 8001163 TI - Vegetative incompatibility in Neurospora: its effect on horizontal transfer of mitochondrial plasmids and senescence in natural populations. AB - We have investigated the horizontal transfer of two mitochondrial plasmids and the Kalilo senescence phenotype in the fungus Neurospora without the use of heterokaryon-forcing markers. The Kalilo senescent state was only transferred between fully-compatible N. crassa strains, but not between strains differing at any of the loci het-c, het-d, het-e or mating-type. However, the linear plasmid kalDNA and the circular plasmid Han-2 were transferred following incompatible vegetative interactions. Our data suggest that vegetative incompatibility due to allelic differences at het-c is more effective in preventing transfer than that due to het-d, het-e or mating-type. Based on these observations we have developed a novel test for assessing vegetative incompatibility between Kalilo and non Kalilo field isolates of N. intermedia. In this procedure combinations of Kalilo and non-Kalilo field isolates of N. intermedia were grown together and tested for senescence. Compatibility is inferred if the young non-Kalilo strain dies along with the senescent Kalilo strain, whereas incompatibility is inferred when the Kalilo strain dies without imposing its senescent state onto the non-Kalilo strain. Our results suggest that each of the nine Kalilo strains tested is incompatible with each of 20 non-Kalilo isolates from the same N. intermedia population of the Hawaiian island of Kauai. However, the observed incompatibility did not completely prevent cytoplasmic exchange, and in several cases plasmid transfer could be detected. PMID- 8001162 TI - Mutations in cyr1 and pat1 reveal pheromone-induced G1 arrest in the fission yeast Schizosaccharomyces pombe. AB - Investigations into sexual differentiation and pheromone response in the fission yeast Schizosaccharomyces pombe are complicated by the need to first starve the cells of nitrogen. Most mating-related experiments are therefore performed on non dividing cells. Here we overcome this problem by using two mutants that bypass the nutritional requirements and respond to the M-factor mating pheromone in rich medium. The first mutant lacks the cyr1 gene which encodes adenylate cyclase and these cells contain no measurable amounts of cAMP. When M-factor is added to a growing h+ cyr1- strain it causes a transient G1 arrest of cell division, transcription of mat1-Pm, and elongation of the cells to form shmoos. The second mutant contains the temperature-sensitive pat1-114 allele. At 30 degrees C this mutant was previously shown not only to bypass the nutritional signal but also to stop growing in a state derepressed for pheromone-controlled functions. We now report that an h+ pat1-114 strain growing mitotically at 23 degrees C responds to M-factor. This shows that the pat1 protein kinase can be tuned to derepress nutritional signalling while repressing the other stages in the differentiation process. PMID- 8001164 TI - The peptide synthetase catalyzing cyclosporine production in Tolypocladium niveum is encoded by a giant 45.8-kilobase open reading frame. AB - Cyclosporin A, a potent and clinically-important immunosuppressive drug (SandimmunR), is synthesized from its precursor amino acids by cyclosporin synthetase, a single multi-functional enzyme. In this study we report the cloning of the corresponding coding region of this synthetase. It contains an open reading frame of 45.8 kb which encodes a peptide with a calculated M(r) of 1,689,243. The predicted gene product contains 11 amino-acid-activating domains that are very similar to one another and to the domains of other peptide synthetases. Seven of these domains harbour N-methyltransferase functions. This is the largest genomic ORF described so far. PMID- 8001165 TI - A luciferase expression system for Physarum that facilitates analysis of regulatory elements. AB - We have developed a transient expression system for the protist Physarum polycephalum based on firefly luciferase. We demonstrate the utility of this system for comparing the activities of different promoters in Physarum amoebae, and also for detecting genetic elements that affect the level of gene expression. This system is likely to facilitate improvements in the stable transformation of this organism. PMID- 8001166 TI - Point mutations in the chloroplast 16s rRNA gene confer streptomycin resistance in Nicotiana plumbaginifolia. AB - In a previous paper we reported the isolation of streptomycin-resistant mutants from Nicotiana plumbaginifolia and presented evidence for chloroplast control of the resistance trait. To understand the molecular basis of the resistance in these mutants, we sequenced three regions in the chloroplast 16s rRNA gene, which correspond to the 5' terminus, the 530 loop, and the 900 stem/loop of Escherichia coli 16s rRNA, and compared them with the sequences of the wild-type. Our results show that: (1) nine mutants have a C to T change at position 912, (2) one mutant (SR1021) has a G to A change at position 885, (3) one mutant has a C to T change at position 526, based on E. coli numbering; and (4) three mutants do not have any change in the regions analyzed. The point mutation detected in SR1021 has not been reported previously. In E. coli 16s rRNA, position 885 is protected from chemical probing by ribosomal protein S12 and is closely juxtaposed with the streptomycin-binding region (positions 912-915) in the predicted secondary structure. It is likely that the G to A transition at this position is a novel mutation for streptomycin resistance. PMID- 8001167 TI - Physical map of the plastid genome of the unicellular red alga Cyanidium caldarium strain RK-1. AB - The physical map of the plasmid genome of the unicellular red alga Cyanidium caldarium strain RK-1 was constructed. The 150-kbp genome was circular and had an inverted repeated region (IR) which contained the genes for 16 s and 23 s ribosomal RNAs, as is usually seen in most plastid genomes. Since C. caldarium is a very "primitive" alga, the results suggest that the ancestral cyanobacteria lost most of its genome as an endosymbiont comparatively early in the process of plastid formation. After that, several genes seem to have been lost from plastid genomes, step by step, during the course of evolution. PMID- 8001168 TI - Cloning and characterization of the European seabass, Dicentrarchus labrax, mitochondrial genome. AB - Mitochondrial DNA (mtDNA) from the European seabass, Dicentrarchus labrax, has been cloned and characterized. Its gene organization was deduced by a comparison of the sequenced termini of different subclones obtained from European seabass mtDNA to the completely-sequenced mtDNAs from carp and freshwater loach. The difference in genome size between the European seabass mtDNA (approximately 18 kb) and most of the other characterized fish mtDNAs (approximately 16.5 kb) is accounted for by the displacement-loop (D-loop). Comparisons have been performed between the derived amino-acid sequences of three sequenced genes, cytochrome c oxidase subunit 2 (COII), NADH dehydrogenase subunit 4L (ND4L) and ATP synthase subunit 8 (ATPase8), from D. labrax, and their counterparts in other fishes and Xenopus laevis. PMID- 8001169 TI - Mitochondrial DNA RFLP and genetical studies of cytoplasmic male sterility in the sunflower (Helianthus annuus). AB - Fifteen sunflower (Helianthus annuus L.) cytoplasmic male-sterile, and a single male-fertile, cytotypes were studied by both mtDNA (mitochondrial DNA) restriction fragment length polymorphism (RFLP) and genetical analysis of male fertility restoration patterns. It was found by multivariate analysis that the two methods of identification of cytoplasmic male sterility (CMS) should be of use in sunflower breeding programs. The RFLP study distinguished 13 groups based on differences in mtDNA organization. DNA molecular diversity occurs both within and between the Helianthus species from which the steriles originate. The mitochondrial genes analyzed present specific molecular configurations for each type of sterility studied. The analysis of male-fertility restoration separated the cytotypes into 12 groups. The associations of CMS and inbred restorer lines indicated the presence of specific nuclear genes involved in cytoplasmic male sterility restoration. PMID- 8001170 TI - A new gene encoding tRNA(Pro) (GGG) is present in the chloroplast genome of black pine: a compilation of 32 tRNA genes from black pine chloroplasts. AB - The chloroplast genome of black pine (Pinus thunbergii), a gymnosperm, contains 32 different tRNA genes, 30 of which correspond to those previously identified in tobacco and rice chloroplast genomes. Two additional genes encode tRNA(Pro) (GGG) and tRNA(Arg) (CCG); the former is newly identified while the latter is present in liverwort, Physcomitrella patens and Angiopteris lygodiifolia, chloroplast genomes. Moreover, a partial copy of the split tRNA(Gly) (UCC) gene and full copies of tRNA(His) (GUG), tRNA(Thr) (GGU) and tRNA(Ser) (GCU) genes are present in the large single-copy region of the genome, suggesting extensive rearrangements of the chloroplast genome during evolution. No tRNA genes whose tRNA products can recognize codons CUU/C (Leu) and GCU/C (Ala) have been found. We propose that the 32 tRNAs are sufficient to read all the 61 sense codons in the black pine system using the "two-out-of-three" and the "U:N wobble" mechanisms. PMID- 8001172 TI - Genetic evidence for independence between fermentative metabolism (ethanol accumulation) and yeast-cell development in the dimorphic fungus Mucor rouxii. AB - Three allyl-alcohol-resistant mutants were isolated in the dimorphic fungus Mucor rouxii and characterized with regard to their alcohol dehydrogenase (ADH) activity in vitro and in vivo as well as their ability to execute the morphological alternatives of dimorphism under different environmental stimuli, either in the absence or in the presence of oxygen. These studies indicated that fermentation and yeast-cell development are independent events and that ADH activity is essential for growth of the fungus in the absence of oxygen. Heterokaryon construction and analysis indicated that in the three mutant strains the corresponding genetic alterations are recessive nuclear mutations which behave as allelic in complementation tests. PMID- 8001173 TI - Genetic analysis of DNA fingerprints and virulences in Erysiphe graminis f.sp. hordei. AB - A DNA probe, E9, which has been used extensively in population genetic studies of the barley powdery mildew pathogen, Erysiphe graminis f.sp. hordei, was shown to be homologous to dispersed sequences in the genome of this fungus. In a cross of the isolates CC52 and DH14, fragments with homology to E9 mapped to six clusters of loci. Avirulences matching five resistance genes in barley were controlled by single genes, in accordance with the gene-for-gene hypothesis, while avirulence matching a sixth resistance gene, Mla13, was controlled by two genes. A gene which controls the response to a fungicide, ethirimol, was not linked to any other gene. In all, seven linkage groups, comprising 22 loci, were detected. The results indicate that E9 can be used to identify members of a clone of E.g. f.sp. hordei, but should not be used for quantitative population genetic analysis. PMID- 8001171 TI - Chloroplastic genomes of Ginkgo biloba and Chlamydomonas moewusii contain a chlB gene encoding one subunit of a light-independent protochlorophyllide reductase. AB - We have cloned and sequenced a Chlamydomonas moewusii chloroplastic DNA fragment that includes a 563 amino-acid open reading frame (ORF563, chlB) presenting 89% amino-acid homology with ORF513 from Marchantia polymorpha. It is also homologous to ORF510 from Pinus thunbergii but includes two insertions absent in both M. polymorphia and P. thunbergii. The derived polypeptide is 54% similar to the product of bchB from Rhodobacter capsulatus, identified as one subunit of a light independent NADH-protochlorophyllide reductase. We also isolated and sequenced an homologous chloroplastic gene from the gymnosperm Ginkgo biloba. Northern hybridizations performed on RNA isolated from synchronized Chlamydomonas eugametos cells showed higher expression between the tenth hour of light and the eighth hour of darkness, peaking during the first 2 h of darkness. PMID- 8001174 TI - Highly-efficient transformation of the homobasidiomycete Schizophyllum commune to phleomycin resistance. AB - Regulatory sequences of the glyceraldehyde-3-phosphate-dehydrogenase (GPD) gene from the homobasidiomycete Schizophyllum commune were fused to the coding sequence of the ble gene from Streptoalloteichus hindustanus, which codes for a phleomycin-binding protein. The resulting construct transformed S. commune to phleomycin resistance at a high frequency (up to 10(4) transformants/microgram DNA per 10(7) protoplasts) when regeneration was done in 0.5 M MgSO4. A similar construct with regulatory sequences from Aspergillus nidulans failed to give transformants, showing the importance of homologous regulatory sequences for the expression of genes in S. commune. The homologous GPD promoter could be deleted up to position -130 without any effect on the number of phleomycin-resistant transformants. This is the first effective stable transformation system in a homobasidiomycete employing antibiotic resistance. PMID- 8001175 TI - Reversion of a long-living, undifferentiated mutant of Podospora anserina by copper. AB - The Podospora anserina nuclear mutant grisea displays an undifferentiated growth phenotype (diminished production of aerial hyphae), is female sterile (lack of perithecia), has a prolonged life-span compared to the wild-type strain, and lacks detectable phenoloxidase (laccase and tyrosinase) activity. Reversion of all of these characteristics to those of the wild-type phenotype was accomplished by supplementing the growth medium with extra amounts of copper salts. These results indicate that the primary defect of the grisea strain is in its copper uptake and/or distribution in the cells. PMID- 8001176 TI - Mapping of additional markers in fission yeast, especially fus1 and three mfm genes. AB - The following genes of the fission yeast Schizosaccharomyces pombe have been mapped by tetrad analysis--chromosome arm I-L: mfm2, rad24, rad25; I-R: abc1, fus1, mfm1; II-L: mfm3; II-R: mam1, rad13. A hot-spot of meiotic recombination although not quite so active as suggested by previous maps, may be located between rad25 and aro5 on I-L. PMID- 8001177 TI - Mistranslation of human phosphoglycerate kinase in yeast in the presence of paromomycin. AB - Missense errors in the translation of mRNAs in Saccharomyces cerevisiae were screened by looking for charge heterogeneity of proteins on two-dimensional gels resulting from the substitution of charged and neutral amino acids. No such mistranslation was detected in wild-type yeast strains grown in the presence of the translational error-inducing antibiotic paromomycin. However, paromomycin induced mistranslation of a heterologous mRNA, encoding human phosphoglycerate kinase expressed in yeast, was seen. We suggest that the combination of error prone translation of a heterologous mRNA, and growth in the presence of paromomycin, leads to an accumulation of mistranslated proteins that can be detected by two-dimensional gel electrophoresis. PMID- 8001178 TI - Lipid domains in model and biological membranes. AB - Lipid domains that occur within biological of model membranes encompass a variety of structures with very different lifetimes. The separation of membrane lipids into compositional domains can be due to lateral phase separation, immiscibility within a single phase, or interaction of lipids with integral or peripheral proteins. Lipid domains can affect the extent and rate of reactions in the membrane and provide sites for the activity of specialized proteins. Domains are likely to be involved in the process of lipid sorting to various cellular membranes, as well as in other processes which involve membrane budding or invagination. PMID- 8001179 TI - Lipid domains and lipid/protein interactions in biological membranes. AB - In the fluid mosaic model of membranes, lipids are organized in the form of a bilayer supporting peripheral and integral proteins. This model considers the lipid bilayer as a two-dimensional fluid in which lipids and proteins are free to diffuse. As a direct consequence, both types of molecules would be expected to be randomly distributed within the membrane. In fact, evidences are accumulating to indicate the occurrence of both a transverse and lateral regionalization of membranes which can be described in terms of micro- and macrodomains, including the two leaflets of the lipid bilayer. The nature of the interactions responsible for the formation of domains, the way they develop and the time- and space-scale over which they exist represent today as many challenging problems in membranology. In this report, we will first consider some of the basic observations which point to the role of proteins in the transverse and lateral regionalization of membranes. Then, we will discuss some of the possible mechanisms which, in particular in terms of lipid/protein interactions, can explain lateral heterogenities in membranes and which have the merit of providing a thermodynamic support to the existence of lipid domains in membranes. PMID- 8001180 TI - Modulation of rhodopsin function by properties of the membrane bilayer. AB - A prevalent model for the function of rhodopsin centers on the metarhodopsin I (MI) to metarhodopsin II (MII) conformational transition as the triggering event for the visual process. Flash photolysis techniques enable one to determine the [MII]/[MI] ratio for rhodopsin in various recombinant membranes, and thus investigate the roles of the phospholipid head groups and the lipid acyl chains systematically. The results obtained to date clearly show that the pK for the acid-base MI-MII equilibrium of rhodopsin is modulated by the lipid environment. In bilayers of phosphatidylcholines the MI-MII equilibrium is shifted to the left; whereas in the native rod outer segment membranes it is shifted to the right, i.e., at neutral pH near physiological temperature. The lipid mixtures sufficient to yield full photochemical function of rhodopsin include a native like head group composition, viz, comprising phosphatidylcholine (PC), phosphatidylethanolamine (PE), and phosphatidylserine (PS), in combination with polyunsaturated docosahexaenoic acid (DHA; 22:6 omega 3) chains. Yet such a native-like lipid mixture is not necessary for the MI-MII conformational transition of rhodopsin; one can substitute other lipid compositions having similar properties. The MI-MII transition is favored by relatively small head groups which produce a condensed bilayer surface, viz, a comparatively small interfacial area as in the case of PE, together with bulky acyl chains such as DHA which prefer a relatively large cross sectional area. The resulting force imbalance across the layer gives rise to a curvature elastic stress of the lipid/water interface, such that the lipid mixtures yielding native-like behavior form reverse hexagonal (HII) phases at slightly higher temperatures. A relatively unstable membrane is needed: lipids tending to form the lamellar phase do not support full native-like photochemical function of rhodopsin. Thus chemically specific properties of the various lipids are not required, but rather average or material properties of the entire assembly, which may involve the curvature free energy of the membrane-lipid water interface. These findings reveal that the membrane lipid bilayer has a direct influence on the energetics of the conformational states of rhodopsin in visual excitation. PMID- 8001181 TI - Lipid dynamics and peripheral interactions of proteins with membrane surfaces. AB - A large body of evidence strongly indicates biomembranes to be organized into compositionally and functionally specialized domains, supramolecular assemblies, existing on different time and length scales. For these domains and intimate coupling between their chemical composition, physical state, organization, and functions has been postulated. One important constituent of biomembranes are peripheral proteins whose activity can be controlled by non-covalent binding to lipids. Importantly, the physical chemistry of the lipid interface allows for a rapid and reversible control of peripheral interactions. In this review examples are provided on how membrane lipid (i) composition (i.e., specific lipid structures), (ii) organization, and (iii) physical state can each regulate peripheral binding of proteins to the lipid surface. In addition, a novel and efficient mechanism for the control of the lipid surface association of peripheral proteins by [Ca2+], lipid composition, and phase state is proposed. The phase state is, in turn, also dependent on factors such as temperature, lateral packing, presence of ions, metabolites and drugs. Confining reactions to interfaces allows for facile and cooperative large scale integration and control of metabolic pathways due to mechanisms which are not possible in bulk systems. PMID- 8001182 TI - Lipid bilayer heterogeneities and modulation of phospholipase A2 activity. AB - The regulation of phospholipase A2 (PLA2) activity toward synthetic vesicular substrates is a model for the modulation c enzyme function by biological membranes. PLA2's catalytic rate toward membrane phospholipids can be modified by several order of magnitude by altering the membrane's composition and structure. The physical basis of this sensitivity is the subject of thi report. The results described here imply that the salient features of membrane-structure which modulate PLA2 activity include compositional phase separation; membrane curvature and, possibly, curvature-associated defects; and dynamic product inhibition due to limitations imposed by the rate of lateral diffusion of lipid in the membrane. Furthermore, it is shown that the effects of membrane structure on the catalytic rate are not exerted merely by enhancing association of PLA2 with the membrane surface: a membrane-bound inactive state is spectroscopically identified. Finally, these results are discussed in the context of some published models for the role of membrane structure in the regulation of membrane-bound enzymes. PMID- 8001184 TI - Dynamical order and disorder in lipid bilayers. AB - Various order and disorder phenomena in lipid bilayers are considered as they arise due to the very many-particle character of the bilayer. Particular attention is paid to dynamically maintained order in terms of lateral density- and compositional fluctuations that lead to dynamic heterogeneity, local structure, and lipid-domain formation on length scales of 10-1000 A. The influence of cholesterol and various drugs on the local structure is described. A discussion is presented of the possible role played by lipid order and disorder phenomena for the functional dynamics of membranes. PMID- 8001183 TI - Interactions between DNA replication-related proteins and phospholipid vesicles in vitro. AB - DNA and phospholipids share a common motif recognizable by proteins. It has been my hypothesis that there are DNA binding proteins which interact with phospholipid membranes and that their activities in DNA replication, transcription, and recombination, are likely to be regulated by phospholipids. I describe here examples of replication-related proteins, the activities of which are modified by acidic phospholipids in vitro. PMID- 8001185 TI - Dipole potential of lipid membranes. AB - Of the individual potentials which comprise the potential profile of a membrane, the least well understood is the dipole potential. In general, the dipole potential is manifested between the hydrocarbon interior of the membrane and the first few water layers adjacent to the lipid head groups. Changes in dipole potential caused by spreading a lipid at an air- or oil-water interface can be measured directly and the dipole potential of bilayers can be estimated from the conductances of hydrophobic ions. For a typical phospholipid, like phosphatidylcholine, its measured value is approximately 400 mV in monomolecular films and approximately 280 mV in bilayer membranes, with the hydrocarbon region being positive relative to the aqueous phase. The difference between dipole potentials measured in monolayers and bilayer membranes appears to arise from the use of the lipid-free air- or oil-water interface as the reference point for monolayer measurements and can be corrected for. The species-specific correction term is a lipid concentration-independent potential, the existence of which suggests the ability of lipid headgroups to globally reorganize water structure at the interface. The dipole potential arises from the functional group dipoles of the terminal methyl groups of aliphatic chains, the glycerol-ester region of the lipids and the hydrated polar head groups. Classical methods for obtaining partial dipole moments for each of the three contributing regions are all based on questionable assumptions and give conflicting results. More sophisticated mean field models of dipole potential origin recognize the important role of interfacial water in determining its value but still cannot adequately describe the microscopic nature of the interactions from which it arises. In part this is because the dipole potential develops in a region over which the dielectric constant of the medium is changing from 2 to 80. Despite of our limited understanding of the dipole potential, it is an important regulator of membrane structure and function. Membrane-membrane and membrane-ligand interactions are regulated by the hydration force, the value of which can be related to the dipole potential of the membrane. For thermotropically phase-separated or multicomponent membranes the size and shape of lipid domains is controlled by the balance between the line tension at the domain borders and the difference in dipole density between the domains. Line tension tends to make the domains compact and circular whereas dipole repulsion promotes transitions to complex domain shapes with larger perimeters.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8001186 TI - Polymer-induced membrane fusion: potential mechanism and relation to cell fusion events. AB - Poly(ethylene glycol) (PEG) is used widely to mediate cell-cell fusion in the production of somatic cell hybrids and in the fusion injection of macromolecules into cultured cells from erythrocytes or liposomes. However, little is known about the mechanisms by which PEG induces fusion of cell membranes, making its use much more an art than a science. This article considers possible molecular events involved in biomembrane fusion and summarizes what we have learned about these in recent years from studies of fusion of well-defined model membranes. In addition, it recounts observations made over the past several years about the process of PEG-mediated fusion of model membranes. These observations have defined the process to an extent sufficient to allow us to propose a model for the molecular events involved in the process. It is suggested that dehydration leads to asymmetry in the lipid packing pressure in the two leaflets of the membrane bilayer leading to formation of a single bilayer septum at a point of close apposition of two membranes. The single bilayer septum then decays during formation of the initial fusion pore. Agents that enhance or alleviate the dehydration-induced asymmetric packing stress will favor or inhibit fusion. Although the proposed picture is consistent with much accumulated data, it is not yet proven; experiments must now be devised to test its details. Finally, the proposed model is discussed in terms of potential implications for the mechanisms available to a cell in controlling more complex in vivo cell fusion processes such as endocytosis, exocytosis, protein sorting/transport, and viral budding/infection. PMID- 8001187 TI - [Neoadjuvant chemoradiotherapy in esophageal cancer]. AB - From June 1987 to December 1993 in our Institute we treated with neoadjuvant chemo-radiotherapy 94 patients with esophageal squamous carcinoma. The neoadjuvant protocol consisted in 3000 cGy and two cycles of chemotherapy (5-FU, 1000 mg/m2, 100 mg/m2 DDP). At the end of this treatment patients underwent surgery. Operability rate was 76.6%, post-operative morbidity was not affected by the neoadjuvant treatment and post-operative mortality rate was 9.5%. Histopathology showed in 15 cases no residual disease (T0) and in 12 patients minimal residual of disease, with isolated neoplastic microfoci in the esophageal wall. The longest survival was of seventy months with medium follow-up of 16.8 months. Overall actuarial survival (Kaplan-Meier test) at one, two, three years were 54%, 34%, and 23% respectively. Our experience showed a better survival of the patients treated with surgery alone, a better operability and resectability rates. However, it is mandatory to wait for the results of perspective randomized studies to evaluate the real advantages of this treatment. PMID- 8001188 TI - [Cancer of the cervical esophagus: integrated therapy and surgical treatment]. AB - From July 1979 to December 1990, 68 consecutive patients with resectable esophageal cancer were treated at our Institute. Until May 85 standard treatment was total laryngectomy and proximal or total esophagectomy, thereafter, to preserve the larynx, primary concomitant chemotherapy and radiotherapy followed by salvage resection in case of persistent disease or local recurrence was the standard regimen. Primary concomitant radio-chemotherapy consisted of traditional radiotherapy (30 + 20 Gy over 7 weeks) with 4 courses of chemotherapy (5FU 1000 mg/sqm 24-hour infusion, days 1 to 4 and CDDP 100 mg/sqm, day 1). 39 patients underwent standard primary total laryngo-pharyngo-esophagectomy, and after May 1985, 29 underwent standard concomitant radiochemotherapy and 16 excluded patients (5 for medical contraindications, 4 for previous partial or total laryngectomy, and the remaining 7 for location of the tumor only in the precricoid) underwent primary resection as second choice treatment. After 40 months of median follow-up 6/39 underwent salvage resection. Iatrogenic mortality (hospital and distant mortality related to the treatment) was 10% (9/68), 13% (5/39) for standard and second choice primary resection and 10% (3/29) for concomitant radiochemotherapy (2 death) and salvage resection (1 death). For overall the patients the median survival was 16 months, without any difference for the patients treated before or after May 85, with minimal difference of the rate of 5 year survival (21% vs 19%), but nearly 50% of the long survivors treated after May 85 is speaking with the larynx. PMID- 8001189 TI - [Limited surgery in cancer of the hypopharynx and cervical esophagus: role of autotransplants of the intestinal loop and skin flaps]. AB - The cervical esophageal region can be involved by several cancer types as primary malignancies of the hypopharynx and cervical esophagus, locally advanced tumors of the larynx and thyroid, and neoplastic recurrence after laryngectomy for cancer. These situations often require complex surgical procedures, and the integrated use of multiple surgical techniques or multistage operations. It is often a limit-type surgery that requires free loop intestinal autotransplants, local and regional skin flaps, and peduncle myocutaneous flaps, and therefore requires specific skill not only in general and thoracic surgery but also in head and neck surgery, plastic surgery and microsurgery. This paper summarizes the experience in the field of cervical esophagus replacement with jejunal free loop autotransplant (23 cases) and cutaneous or myocutaneous flaps (23 cases) at the "Centro Regionale Veneto per le Malattie dell'Esofago" from 1980 to 1993. PMID- 8001191 TI - [Pulmonary carcinoid tumors]. AB - 27 patients suffering from carcinoid of the lung (18 females and 9 males, middle age 52 years, range 26-68) underwent surgery in our department. The neoplasms were located at the pulmonary hilum in 21 cases. The diagnosis was occasional in 6 cases, cough (51.8%) and recurrent bronchitis (37%) were the most frequent symptoms. No instances of carcinoid syndrome were detected. Preoperative staging ruled out pathologic mediastinal lymph nodes or hematogenous metastases. 26 patients underwent complete excision of the neoplasm (11 lobectomies, 9 pneumonectomies, 4 bilobectomies, 1 segmental resection, 1 bronchial wedge resection). Histologically, 4 cases were categorized as atypical carcinoids. Two patients died within 1 year, one suffering from atypical carcinoid because of disease progression, and an other one (suffering from atypical carcinoid) who underwent only at exploratory thoracotomy followed by chemotherapy. A patient suffering from typical carcinoid died within 1.5 years because of gallbladder carcinoma. From our experience and from the literature review it appears that carcinoids has to be considered as malignant neoplasms and treated according to. PMID- 8001192 TI - [Iatrogenic rupture of the esophagus: presentation of several cases]. AB - Four cases of iatrogenic rupture of the oesophagus are presented. The site of the lesion was in the cervical tract in 1 case and in the thoracic tract in the other 3 cases. Their etiology was pneumatic endoscopic dilatation for achalasia in 2 cases, endoscopic insertion of a Celestin tube for carcinoma of the thoracic tract of the oesophagus in 1 case, and diagnostic endoscopy in the last one. Instrumental findings were relevant in all cases. All patients underwent surgery. In the patients suffering from achalasia, the rupture was repaired by a patch of the gastric fundus. The patient suffering from carcinoma underwent an oesophageal resection, the one with cervical perforation underwent a mediastinal drainage. There were no deaths or considerable post operating complications. In a patient suffering from achalasia gastro-oesophageal reflux was demonstrated after some months following the operation. PMID- 8001190 TI - [Pulmonary carcinosarcoma]. AB - Sarcomatoid carcinomas of the lung are uncommon neoplasms; the concurrent presence of malignant epithelial and sarcomatoid spindle cell components show a high malignancy. Lymph node metastases at presentation is an important prognostic factor, on the other way the most patients with sarcomatoid carcinoma of the lung usually presented at an advanced stage that needed a complementary therapy. The Authors report about one surgical case of pulmonary carcinosarcoma recently observed without lymph node metastases; the literature is reviewed and the histogenesis is discussed. PMID- 8001193 TI - [Primary germinal tumors of the mediastinum: our experience in 9 cases]. AB - 9 patients (8 males 1 female, middle age 24.3 years, range 20-41) affected by primary mediastinal germ cell tumor were surgically treated in our department. They were 4 seminomas, 2 embryonal carcinomas, 1 malignant teratoma and 2 benign teratomas. Three patients were asymptomatic; cough, dyspnea and chest pain were the most frequently observed symptoms. The staging work-up did not show signs of metastatic disease in the malignant types. Benign teratomas underwent complete excision. In one patient suffering from seminoma radiotherapy and chemotherapy caused complete remission of the disease. In the others cases remission of the neoplasm was obtained by resection and adjuvant therapy in 3 cases, by neoadjuvant treatment and excision of the residual mass in 3 cases. Among the patients suffering from seminoma, 2 are dead at 60 months since initial treatment and 2 are alive at 132 and 120 months respectively. Among the patients with malignant nonseminomatous tumours, 2 are alive at 60 and 36 months and 1 patient is dead at 13 months. Two patients with benign teratoma are alive at 189 and 168 months respectively. At present a multimodality treatment including surgery, radiotherapy and cisplatin-based combination chemotherapy, give the most satisfactory results in the treatment of malignant mediastinal germ cell tumours. PMID- 8001194 TI - [Endoscopic ultrasonography in preoperative staging of esophageal cancer]. AB - Thirty-two consecutive patients with esophageal carcinoma (squamous cell carcinoma: 23, adenocarcinoma: 9) were pre-operatively examined by endoscopic ultrasonography (EUS) in order to evaluate the accuracy of this diagnostic procedure in loco-regional staging. Six patients were not operated on, due to a poor general conditions or widespread tumor disease and were not included in this study. Results of EUS staging from the remaining patients were compared with intra-operative exploration and histopathological evaluation of resection specimens. Seven stenosing tumors were not traversable by echoendoscope. In such cases the lesion was visualized only in part by scanning the top of the stenosis. The overall EUS accuracy in T staging was 80.7% (75% in T2 stage, 90.9% in T3, 71.4% in T4). Three tumors were overstaged; two not traversable stenosing tumors were understaged. The overall accuracy in N staging was 73% (sensitivity 77.7%, specificity 62.5%). For celiac nodes EUS sensitivity was only 57.1%. Authors conclude that the presence of a not traversable stenosis is still a limit for EUS in diagnosing infiltration of adjacent structures as well as in detecting lymph node metastases. PMID- 8001195 TI - [Role of video-thoracoscopy in the diagnostic specification of thoraco-pulmonary diseases]. AB - Video-thoracoscopy can be used for diagnostic purposes when the other non invasive methods are not satisfactory for an accurate histological diagnosis, in lung and pleural pathology. Cases observed in last six months and subject to surgery are discussed. PMID- 8001196 TI - [Thoracoplasty today. Review of a technique of the past]. AB - Thoracoplastic operations had ruled the field in the past as treatment of choice in the surgical antituberculous collapse therapy; they have had a notable revival during the last years as an efficient therapeutic modality in the treatment of chronic empyemas of the most various etiologies. They are thoracoplasties done with particular modalities, imposing, setting out case by case to suppress the infected pleural space. It is usually joined with a thoracotomy and it permits also the execution of other surgical intrathoracic manoeuvres such as decortications, treatment of fistulas, myoplasties. Situations such as chronic empyemas, without any solution before, have found a brilliant solution by the use of this operation. PMID- 8001197 TI - Cumulative effect of repetitive ischemia: pathophysiological findings. AB - The cumulative effect of ischemia on the brain was investigated in cats using a repetitive transient global ischemia model. The cats were submitted to three series of repetitive ischemia of 5.0, 7.5 and 10.0-minute durations at 1-hour intervals by intrathoracic clamping of the innominate and subclavian arteries. Pathophysiological changes during and after the ischemic episodes were evaluated by monitoring the electroencephalograms (EEG), cerebral blood flow (CBF), specific gravity and 31P-MR spectroscopy (MRS). Transient 5.0, 7.5, and 10.0 minute ischemias appeared to produce a slightly more severe energy failure on the 31P MRS measurement in the animals that had previously experienced an ischemic injury than those that had not. Additionally, repetition of ischemic episodes at 1-hour intervals led to a progressive lengthening of the duration of the spontaneous electrocortical suppression that followed each ischemic episode. However, preischemic hypoxia (5% O2 for 5 minutes) resulted in minor changes in the levels of phosphocreatine and intracellular inorganic phosphate on the MRS measurement, otherwise the EEG activity declined progressively. This shut-down response of the EEG can be concluded to serve in preserving the energy state of the brain although it is not capable of preventing the development of postischemic brain edema and neuronal death. PMID- 8001198 TI - [A short history of Rene Groupil, patron saint of anesthetists]. AB - Born in 1608 near Angers, France, Rene Goupil looked after the native people at Sillery, Quebec between 1640 and 1642 as surgeon and donne. Ambushed and captured by Mohawk warriors, he was killed in September 1642 near Auriesville NY. He was canonized in 1930. The life of Goupil is reviewed with regards to primitive medicine of the 17th century. In 1951, american nurse anesthetists chose Rene Goupil, health worker and saint of North America, as the patron saint of the anaesthetists. Since, he has been recognized by more and more practitioners of anaesthesia. PMID- 8001199 TI - Don't let the Bain take the blame. PMID- 8001200 TI - Tracheal obstruction. PMID- 8001201 TI - Laryngeal mask airway in cardiac surgery. PMID- 8001202 TI - Tracheo-bronchial angles in infants and children. PMID- 8001203 TI - Oral cyclosporine-vecuronium interaction. PMID- 8001204 TI - Anaesthetists overestimate blood loss. PMID- 8001205 TI - Perioperative care of the cocaine-abusing patient. PMID- 8001206 TI - The laryngeal mask airway in anaesthesia. PMID- 8001207 TI - Evaluation of cost minimization strategies of anaesthetic drugs in a tertiary care hospital. AB - A survey was undertaken to compare anaesthetic drug expenditures over a three year period, to evaluate the impact of strategies offered to curtain continuously rising drug costs. Suggestions to control rising expenditures were based primarily on education of staff and residents regarding drug costs, emphasizing rational use of the more expensive drugs, and minimizing drug wastage. To assess the impact of these measures, a review of annual hospital budgets, global pharmacy expenditures, and anaesthetic drug expenditures was conducted for the period 1991 to 1993. Both absolute and proportional costs of anaesthetic drugs were compared, by year, according to six major classes: opioid analgesics (OA), muscle relaxants (MR), inhalational anaesthetic drugs (INH), intravenous anaesthetic drugs (i.v.), local anaesthetic drugs (LA) and a category labelled other drugs (OTH). In addition, the utilization patterns and unit price changes were compared for each drug for the periods 1991-92, and 1992-93. Total hospital drug costs increased from $7.1 M to $8.5M over the three years. During the same period, the cost of anaesthetic drugs decreased from $379K to $361K, despite an augmentation in annual case load from 12,507 to 13,076 surgical procedures. For the entire survey period, the mean cumulative anaesthetic drug cost was 4.6% of the pharmacy budget, or 0.24% of the hospital budget. Analysis by drug class revealed a $51K decrease in expenditures on OA. due to decreased utilization of fentanyl and alfentanil, and a decrease in the price of fentanyl. The increased expenditure on INH drugs was primarily due to an increase in acquisition costs.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8001208 TI - Different priming techniques, including mivacurium, accelerate the onset of rocuronium. AB - Different priming sequences of equipotent doses of rocuronium and mivacurium on the onset of maximum neuromuscular block and intubating conditions were compared with those obtained after succinylcholine. During thiopentone-fentanylnitrous oxide anaesthesia, 70 patients were randomly assigned into seven groups. Group I received mivacurium 0.15 mg.kg-1 as a single bolus dose. Group II received a priming dose of mivacurium 0.015 mg.kg-1 followed three minutes later by mivacurium 0.135 mg.kg-1. Group III received rocuronium 0.6 mg.kg-1 as a single bolus dose, and Group IV received an initial dose of rocuronium 0.06 mg.kg-1 followed by rocuronium 0.54 mg.kg-1. Group V received a priming dose of mivacurium 0.015 mg.kg-1 followed by rocuronium 0.54 mg.kg-1. Group VI received an initial dose of rocuronium 0.06 mg.kg-1 followed by mivacurium 0.135 mg.kg-1. Group VII received succinylcholine 1.0 mg.kg-1. Groups I, III, and VII received a placebo injection before the administration of the neuromuscular blocking drug. Additional thiopentone 2 mg.kg-1 iv was given 30 sec before intubation. Onset times (mean (95% confidence interval)) after priming a rocuronium block with either rocuronium (73 (57-90) sec) or mivacurium (58 (47-69) sec) were similar to those after succinylcholine (54 (40-68) sec), and were shorter (P < 0.01) than that observed in other groups. Intubating conditions were not different between the groups. The duration of neuromuscular block was shortest with succinylcholine. It is concluded that priming a rocuronium block with either mivacurium or rocuronium resulted in a neuromuscular block comparable to that of succinylcholine in both the onset of action and intubating conditions. PMID- 8001210 TI - The Vancouver sedative recovery scale for children: validation and reliability of scoring based on videotaped instruction. AB - We originally developed and tested the Vancouver Sedative Recovery Scale (VSRS) to measure recovery from sedation following paediatric open heart surgery and reported excellent clinical inter-observer reliability. We now report a new study using videotape instruction of novice raters and videotaped case examples to determine whether the instruction produces adequate skill with the VSRS. Inter rater reliability was assessed using videotapes of 16 children across a range of ages (six months to six years), and all levels of sedation (unresponsive to fully awake). Variably randomized subsets of six of the 16 test cases were randomly assigned to be rated by each of 16 video-instructed ICU staff volunteers, according to a balanced incomplete block design, such that every pair of raters assessed two children in common. The validity of the ratings from the video instructed raters was assessed by comparison with "gold standard" scores from two experts who rated all 16 children clinically as the test cases were videotaped. The experts were in agreement themselves (intraclass correlation of 0.976). The correlation between the novice scores (average of six ratings per video) and the live clinical scores (average of two expert ratings) was 0.977 over the 16 test cases. On average, the mean expert rating was slightly higher, but the difference was negligible. (The differences between the mean ratings of the experts and novices for 13 of the 16 videos are very close to zero, while the other three differences, from technically less good videos, are two standard deviations away from zero). The VSRS, video instruction method and incomplete block design may be of use to other clinicians and investigators. PMID- 8001209 TI - Neuromuscular effects of vecuronium and neostigmine in Montreal and Paris. AB - The potency of vecuronium was reported to be greater in Montreal than in Paris. This study was designed to determine whether there were differences in onset, duration, and reversibility with neostigmine between both centres. Twenty ASA I or II adults (ten men, ten women), aged 18-65 yr were studied in each of the two cities, during a standard thiopentone-fentanyl-nitrous oxide (60-70%) - isoflurane 0.5% end-tidal anaesthetic. Train-of-four stimulation was applied every 20 sec to the ulnar nerve at the wrist and the force of contraction of the adductor pollicis muscle was measured. Vecuronium, 0.1 mg.kg-1, was given as a bolus, and neostigmine, 0.04 mg.kg-1, was administered, with atropine 0.02 mg.kg 1, at 25% first twitch height recovery. Onset time to maximum blockade was (mean +/- SD) 3.9 +/- 1.3 min in Paris vs 4.5 +/- 1.3 min in Montreal (NS). Duration from injection to 25% first twitch recovery was shorter (28.5 +/- 6.8 min) in Paris than in Montreal (39.1 +/- 7.3 min) (P < 0.0001). Time from injection of neostigmine to a train-of-four ratio of 70% was not different in Paris (6.3 +/- 2.2 min) from Montreal (5.6 +/- 1.9 min). It is concluded that the duration of an "intubating" dose of vecuronium is longer in Montreal, but, when given at 25% first twitch recovery, neostigmine has the same efficacy in Montreal as in Paris. PMID- 8001211 TI - [The use of 2-chloroprocaine for a combined lumbar plexus and sciatic nerve block]. AB - A combination of the lumbar plexus and sciatic nerve blocks using 2 chloroprocaine (2-CP) for unilateral lower extremity anaesthesia was studied. The purpose of this work was to evaluate the efficacy of 2-CP for ambulatory surgery of short duration with this combination of blocks. Twenty-five patients ASA 1 and 2 were studied. The techniques used have been described by Winnie and Labat. A total dose of 60 ml of 2-CP 3% was injected. Latency time before anaesthesia was approximately seven min for the lumbar plexus and 14 min for the sciatic nerve. The mean duration of the motor block was 71 +/- 16 min, 76.8 +/- 15.3 min and 75 +/- 12.7 min for the sciatic, femoral and obturator nerves respectively. The mean duration of the sensory block was 88.7 +/- 20.9 min, 83.3 +/- 16.4, 79.7 +/- 17.8 min and 93.7 +/- 22 min for the sciatic, femoral, obturator and lateral femoral cutaneous nerves respectively. Success rate was 92% and no major complication occurred. We conclude that a combination of the lumbar plexus and the sciatic nerve blocks with 2-CP is a useful technique for ambulatory surgery of short duration. PMID- 8001212 TI - Omeprazole reduces preoperative gastric fluid acidity and volume in children. AB - To explore the effects of oral omeprazole on preoperative gastric fluid pH and volume in children, 104 healthy in-patients aged 4-9 yr were randomly allocated to four groups (n = 26). Subjects in the Omeprazole-Omeprazole Group received two doses of omeprazole (20 mg per dose), those in the Placebo-Placebo Group, two doses of placebo, those in the Placebo-Omeprazole and Omeprazole-Placebo Groups, one dose each of the two preparations by mouth. For each treatment regimen, the first medication was administered at 9:00 p.m. on the night before surgery and the second at 5:30 a.m. on the morning of the day of surgery (three hours preoperatively). Children undergoing elective surgery were offered 10 ml.kg-1 of apple juice three hours before induction of anaesthesia. After induction of anaesthesia and tracheal intubation, gastric fluid was aspirated through a large bore, multiorifice orogastric tube and analyzed for pH and total fluid volume. The administration of omeprazole at bedtime before surgery increased gastric pH (3.3 +/- 1.3 vs 2.0 +/- 0.6, P < 0.05) in comparison with placebo, as did two doses of omeprazole (pH = 4.8 +/- 1.6, P < 0.05). A single dose of omeprazole administration on the morning of the day of surgery failed to increase gastric pH. There was a reduction in the number of children with a pH < 2.5 and a volume > 0.4 ml.kg-1 in the Omeprazole-Omeprazole and Omeprazole-Placebo Groups, compared with the Placebo-Placebo or Placebo-Omeprazole Groups.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8001214 TI - Intraoperative pulmonary oedema in a young cocaine smoker. AB - This is a case of a 28-yr-old man who underwent general anaesthesia for emergency repair of a right lid laceration and lacrimal apparatus. Following induction of anaesthesia and local nasal application of phenylephrine (0.25%) he developed transient elevation of blood pressure, which was treated immediately with labetalol. Subsequently the patient developed acute pulmonary oedema which responded to treatment with morphine and furosemide. The diagnosis of pulmonary oedema was confirmed by blood gas studies, chest x-ray and serial echocardiograms. Subsequent investigation revealed that he was a cocaine user, as the urine tested positive for cocaine. Considering that the patient was young and otherwise healthy and that the hypertension was transient, it is unlikely that phenylephrine was the main cause of pulmonary oedema. Cardiac morbidity was most likely precipitated by the interaction of phenylephrine-induced hypertension with a cocaine-depressed myocardium. PMID- 8001215 TI - Haemoglobin Hammersmith precludes monitoring with conventional pulse oximetry. AB - We report a case of a 15-yr-old North American Indian female with haemoglobin Hammersmith, scheduled for elective tonsillectomy, whose arterial oxygen saturation could not be reliably monitored perioperatively because of technical limitations of conventional dual wavelength pulse oximetry. The patient was chronically icteric. She had an atrial septal defect with a small L-->R shunt demonstrated by echocardiography. On arrival in the operating room pulse oximetry (Nellcor-Model N100) demonstrated a saturation of 45% whilst breathing room air. Her oxygen saturation increased to 60% whilst breathing 100% oxygen via a face mask. An arterial blood gas performed whilst breathing 100% oxygen revealed a PaO2 of 418 mmHg. Tonsillectomy was completed uneventfully under general anaesthesia. The pulse oximeter did not provide any clinically useful information throughout the case. In conclusion, conventional dual wavelength pulse oximeters cannot give an accurate estimate of oxygenation in patients with haemoglobin Hammersmith. Assessment of oxygenation in these patients requires alternative monitoring techniques. PMID- 8001217 TI - On the design of anaesthesia record forms. AB - The purpose of this report is to develop a rational approach to the design of anaesthesia record forms. The history of anaesthesia record forms was reviewed. A logical approach to the design of an anaesthesia record was developed. The theoretical ideal anaesthetic record was contemplated and criteria were developed for the selection of items to be included in or excluded from the record. Principles were outlined which lead to logical organization of information on the form, improved ergonomics of data entry, and ready access to entered information. A desktop publishing system was used to execute quickly numerous form artwork revision cycles and iteratively converge on a complete design. This approach has resulted in the development and production of a new anaesthesia record for our institution. The record was well accepted by our colleagues. The rationale that has been developed is presented in the hope that it will be useful to others in the process of designing anaesthesia records for their institutions. PMID- 8001216 TI - Thyrotoxicosis factitia in a post-aortocoronary bypass patient. AB - A 52-yr-old man presented with an evolving myocardial infarction and unstable angina. Previously, he had undergone aortocoronary bypass surgery for triple vessel disease and at that time was diagnosed as hypothyroid. He had been refractory to thyroxine treatment and now required 0.3 mg thyroxine daily. On admission, he was hypertensive, tachycardic and found to be thyrotoxic secondary to excess thyroid hormone ingestion. Treatment with iopanoic acid was started. Despite medical therapy he continued to have unstable angina. Coronary angiography confirmed further triple vessel disease with blockage to his previous grafts. He was taken to surgery for coronary revascularization. On arriving in the intensive care unit he developed a thyroid storm. His temperature increased from 36.5 to 39.5 degrees C requiring a cooling blanket and cold irrigation down a nasogastric tube. An esmolol infusion was started to control his persistent tachycardia but this depressed his myocardial contractility. He required amrinone and noradrenaline infusions as further inotropic support. For sedation and muscle relaxation, intravenous propofol infusion and doxacurium were given. Over the following 20 hr the patient's condition stabilized. In conclusion, we describe the use of a short-acting beta blocker to avoid compromising an impaired myocardium during a thyroid storm which we could stop if the patient's cardiac condition deteriorated. In addition, amrinone, a phosphodiesterase inhibitor, was our inotrope of choice as it does not act on the already blocked beta adrenergic system. PMID- 8001218 TI - The most proximal and accurate site for sampling end-tidal CO2 in infants. AB - The most proximal site to sample end-tidal CO2 with reasonable accuracy in infants during pulmonary ventilation using a Mapleson D circuit remains controversial. The utilisation of high fresh gas flow near the site of gas sampling dilutes the expired gas and causes an underestimation of end-tidal CO2. In this study a laboratory model was used to identify, qualitatively and quantitatively, the most proximal site in the Mapleson D circuit where the measurement of end-tidal CO2 is not influenced by mixing with fresh gas. A fresh gas flow rate of between 2 and 15 L.min-1 with a respiratory rate of 20-30.min-1 and a tidal volume of 30-100 ml.min-1 was evaluated. This experiment was divided into two parts. Firstly, an infant lung model was used to visualize the site of mixing between fresh gas and smoke-labelled exhaled gas. Secondly, fresh gas flow and expired gas flow were controlled and the end-tidal CO2 concentration was measured along the length of the anaesthetic circuit to identify the site of mixing of fresh gas and expired gas during steady-state conditions. Three expired gas flows were studied at six fresh gas flows. In all our studies, the rate of fresh gas flow and expired gas flow influenced the site of mixing and degree of dilution but no mixing was observed distal to the point at which the endotracheal tube connector narrows to the diameter of the endotracheal tube (P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8001213 TI - The laryngeal mask airway: its features, effects and role. AB - The laryngeal mask airway was designed as a new concept in airway management and has been gaining a firm position in anaesthetic practice. Numerous articles and letters about the device have been published in the last decade, but few large controlled trials have been performed. Despite widespread use, the definitive role of the laryngeal mask has yet to be established. In some situations, such as after failed tracheal intubation or in anaesthesia for patients undergoing laparoscopic or oral surgery, its use is controversial. There are a number of unresolved issues, for example the effect of the laryngeal mask on regurgitation and whether or not cricoid pressure prevents placement of the mask. We review the techniques of insertion, details of misplacement, and complications associated with the use of the laryngeal mask. We discuss the features and physiological effects of the device, including the changes in intra-cuff pressure during anaesthesia and effects on blood pressure, heart rate and intra-ocular pressure. We then attempt to clarify the role of the laryngeal mask in airway management during anaesthesia, based on the current knowledge, by discussing the advantages and disadvantages as well as the indications and contraindications of its use. Lastly we describe the use of the laryngeal mask in circumstances other than airway maintenance during anaesthesia: fibreoptic bronchoscopy, tracheal intubation through the mask and its use in cardiopulmonary resuscitation. PMID- 8001219 TI - Halothane and isoflurane preferentially inhibit prostanoid-induced vasoconstriction of rat aorta. AB - In a previous study, we demonstrated that halothane and isoflurane inhibit binding of thromboxane A2 to its receptors on human platelets and thus inhibit prostanoid-induced aggregation strongly. The aim of this study was to determine whether volatile anaesthetics inhibit prostanoid-induced vasoconstriction preferentially. Rat isolated aortic rings were mounted in organ baths and their isometric tension was measured. They were contracted with STA2 (a stable thromboxane A2 analogue), prostaglandin F2 alpha (PGF2 alpha), phenylephrine, and 20 mM KCl, and then exposed to halothane (0.5-3%), isoflurane (0.5-3%), and sodium nitroprusside (SNP, 10(-9)-3 x 10(-7) M). Halothane (2-3%) and isoflurane (2-3%) induced greater relaxation of aortic rings precontracted with STA2 and PGF2 alpha than of those precontracted with phenylephrine (P < 0.01). Halothane induced greater relaxation of rings precontracted with KCl than phenylephrine only at 3%, whereas isoflurance relaxed rings precontracted with KCl more than those with phenylephrine at 0.5, 2 and 3% (P < 0.05). In contrast, SNP relaxed rings precontracted with PGF2 alpha. KCl and phenylephrine equally, but induced smaller relaxations of those precontracted with STA2 (P < 0.05). We conclude that halothane and isoflurane inhibit prostanoid-induced vasoconstriction preferentially, possibly by interacting with prostanoid receptors. PMID- 8001220 TI - Fibreoptic intubation. AB - Although not widely utilized, fibreoptic techniques represent a dramatic advance in the management of the difficult intubation. Particularly suited to the awake patient in the elective setting, fibreoptic intubation can also be useful in selected emergency situations, and can be done under general anaesthesia. In the awake patient fibreoptic intubation maintains a wide margin of safety while producing minimal patient discomfort, but requires adequate local anaesthesia of the airway. Intimate familiarity with the bronchoscope and the anatomy of the upper airway is essential as is careful attention to various aspects of technique. Intubation mannequins can be readily utilized to develop dexterity in bronchoscopic manipulation and intubation workshops are also effective in improving skills. This CME article provides the clinician with a detailed approach to the technique of fibreoptic intubation based on the author's personal experience supplemented by a limited literature review. Fibreoptic intubation is not a difficult skill to master and should be in the armamentarium of all practising anaesthetists. PMID- 8001221 TI - MTS1/CDK4I is altered in cell lines derived from primary and metastatic oral squamous cell carcinoma. AB - The MTS1/CDK4I gene encodes a 16 kDa cyclin kinase inhibitor and maps to chromosome 9p21. Previous studies have suggested the presence of a major tumour suppressor gene at this locus which may be inactivated in head and neck squamous cell carcinoma (HNSCC). To determine the status of this gene in human primary and metastatic HNSCC, we examined the locus and its transcript for abnormalities by polymerase chain reaction (PCR). Out of 14 cell lines studied, four had lost only exon 1, one had lost only exon 2, three had lost both exons 1 and 2, and none of the remaining six lines expressed a normal p16 mRNA. These latter six cell lines expressed p16 transcripts that had suffered deletions ranging in size from 2-16 base pairs. In each case, deletions led to a change of reading frame. Furthermore, in two cases abnormalities in the MTS1/CDK4I gene were identical in cells derived from metastatic tumours as compared to cells derived independently from the corresponding primary tumour. The identical nature of mutations observed in primary tumours and metastases derived from the same patient provides strong evidence that inactivation of p16 function was an in vivo event. PMID- 8001222 TI - The peroxisome proliferator class of non-genotoxic hepatocarcinogens synergize with epidermal growth factor to promote clonal expansion of initiated rat hepatocytes. AB - The mechanisms by which the peroxisome proliferator (PP) class of non-genotoxic carcinogens perturb growth regulation and cause rodent liver cancer are unknown. Using a soft agar cloning assay, we have demonstrated that PPs synergize with the physiological liver mitogen epidermal growth factor (EGF) to cause the clonal expansion of rat hepatocytes associated with the early stages of tumourigenesis. In the presence of EGF (25 ng/ml), the PP nafenopin (100 microM) was able to stimulate a 5-fold increase in the number of colonies (35 colonies/50,000 hepatocytes compared to seven in the control). EGF alone or nafenopin alone gave 11 and 14 colonies respectively. TGF alpha, which acts through the EGF receptor, also synergized with nafenopin, whereas HGF was inactive, despite its potency as an hepatocyte growth factor. The ability to promote colony formation was shared by the potent PP Wyeth-14,643 but not by the less potent compounds methylclofenapate or trichloroacetic acid. TGF beta, a physiological negative regulator of liver growth, was able to inhibit the nafenopin/EGF-stimulated colony formation at 0.25 ng/ml, a concentration below that required for TGF beta induced hepatocyte apoptosis. The colonies formed are derived from and consist of hepatocytes, since they express the hepatocyte-specific marker albumin, although the majority are negative for the PP-induced cytochrome, P4504A1. Pre-treatment in vivo with the genotoxic carcinogen dimethylhydrazine hydrochloride (150 mg/kg) caused a doubling in the number of colonies from 35 to 75/50,000 hepatocytes. Taken together, these data suggest that some PPs act as hepatocarcinogens by synergizing with EGF and/or TGF alpha to promote the clonal expansion of spontaneously initiated hepatocytes. This clonal expansion may be inhibited by TGF beta. Such a synergy may provide a mechanistic basis for the hepatocarcinogenicity of this class of non-genotoxic carcinogens. PMID- 8001223 TI - Mutagenicity of metabolic oxygen radicals in mammalian cell cultures. AB - Reactive oxygen species produced by normal cellular metabolism have been considered to play a causative role in spontaneously occurring genomic instability and carcinogenesis. To study the genotoxic consequences of an enhanced flux of metabolically produced reactive oxygen species, cells may be exposed to hyperoxia (elevated concentrations of oxygen), a condition known to generate high levels of microscopically visible chromosomal damage. Here we assess the mutagenic potential of normobaric hyperoxia in several mammalian cells lines (CHO-K1-BH4 and AS52 Chinese hamster cells and TK6 human lymphoblastoid cells) using different target genes, including hprt, xprt and tk. Exposure of cell cultures to hyperoxia to 10-40% clonogenic cell survival, failed to induce mutations at the hprt and xprt loci. In human TK6 cells, hyperoxia failed to induce normal growing tk mutants, but efficiently induced slow growing tk mutants. The latter type of mutant is supposed to result from very large deletions or mutlilocus events. Our results suggest that elevated levels of endogenous activated oxygen species are inefficient in inducing point mutations or small deletions, but tend to generate gross rearrangements. Mammalian cells under oxidative stress thus exhibit a hyper-recombination phenotype. The carcinogenic impact of metabolic oxygen radical fluxes may thus be based on enhanced mitotic recombination rates, leading to tumor suppressor gene inactivation through 'loss of heterozygosity'. PMID- 8001224 TI - Monitoring exposure to acrylonitrile using adducts with N-terminal valine in hemoglobin. AB - Human exposure to acrylonitrile (ACN), a carcinogen in rats, may occur in industrial settings, through waste water and tobacco smoke. ACN is an electrophilic compound and binds covalently to nucleophilic sites in macromolecules. Measurements of adducts with hemoglobin could be utilized for improved exposure assessments. In this study, a method for quantification of N-(2 cyanoethyl)valine (CEVal), the product of reaction of ACN with N-terminal valine in hemoglobin has been developed. The method is based on the N-alkyl Edman procedure, which involves derivatization of the globin with pentafluorophenyl isothiocyanate and gas chromatographic-mass spectrometric analysis of the resulting thiohydantoin. An internal standard was prepared by reacting valylglycylglycine with [2H3]ACN, spiked with [14C]ACN to a known sp. act. Levels of CEVal were measured in globin from rats exposed to 3-300 p.p.m. ACN in drinking water for 105 days and from humans (four smokers and four non-smokers). CEVal was detected at all exposure levels in the drinking water study. The relationship between adduct level and water concentration was linear at concentrations of 10 p.p.m. (corresponding to an average daily uptake of c. 0.74 mg ACN/kg body wt during the 65 days prior to sacrifice) and below, with a slope of 37.7 pmol CEVal/g globin/p.p.m. At higher concentrations, adduct levels increased sublinearly, indicating saturation of a metabolic process for elimination of ACN. Comparison of adduct formation with the estimated dose (mg/kg/day) of ACN indicated that at low dose (0-10 p.p.m.) CEVal = 0.508 x ACN dose + 0.048 and at high dose (35-300 p.p.m.) CEVal = 1.142 x ACN dose - 1.098. Globin from the smokers (10-20 cigarettes/day) contained about 90 pmol CEVal/g, whereas the adduct levels in globin from non-smokers were below the detection limit. The analytical sensitivity should be sufficient to allow monitoring of occupationally exposed workers at levels well below the current Occupational Safety and Health Administration standard of 2 p.p.m. PMID- 8001225 TI - Evidence for a high-affinity enzyme in rat esophageal microsomes which alpha hydroxylates N'-nitrosonornicotine. AB - The tobacco-specific nitrosamine N'-nitrosonornicotine (NNN) induces esophageal but not liver tumors in the rat. This may in part be due to tissue-specific differences in the activation of this nitrosamine. Therefore, the metabolism of NNN by microsomes from the mucosa of the rat esophagus was characterized and compared to its metabolism by liver microsomes. Esophageal microsomes metabolized NNN to both 4-hydroxy-1-(3-pyridyl)-1-butanone and 2-hydroxy-5-(3 pyridyl)tetrahydrofuran, the products of 2'- and 5'-hydroxylation of the pyrrolidine ring, respectively. This activity required an NADPH-generating system and was inhibited by carbon monoxide, suggesting that it is mediated by a cytochrome P450 enzyme. The apparent KM for total alpha-hydroxylation of NNN by esophageal microsomes was 49 +/- 6.5 microM and Vmax was 113 +/- 3.7 pmol/mg/min. The ratio of 2'-hydroxylation to 5'-hydroxylation was 3.2 +/- 0.5 when the NNN concentration was varied from 1 microM to 2 mM. 2'-Hydroxylation is believed to be the activation pathway responsible for the tumorigenicity of NNN. In contrast, the ratio of 2'- to 5'-hydroxylation of NNN by liver microsomes was between 0.71 and 0.23 depending on the concentration of NNN used. Hepatic microsomal metabolism of NNN was not saturated at 2 mM NNN, the highest concentration of NNN used. These results confirm the existence of an esophageal enzyme with high affinity for alpha-hydroxylation of NNN; it is probably a cytochrome P450. If this enzyme exists in the liver its activity is masked by high KM, high Vmax enzymes which also alpha-hydroxylate NNN. These enzymes are not present in the esophagus. The presence of a low KM esophageal enzyme that 2'-hydroxylates NNN is consistent with the hypothesis that NNN esophageal tumorigenicity is at least in part due to the efficient activation of NNN in this tissue. PMID- 8001227 TI - Lung tumor induction in A/J mice by the tobacco smoke carcinogens 4 (methylnitrosamino)-1-(3-pyridyl)-1-butanone and benzo[a]pyrene: a potentially useful model for evaluation of chemopreventive agents. AB - The purpose of this study was to establish a lung tumor model for the evaluation of chemopreventive agents against lung cancer in smokers. Lung tumor induction in A/J mice by 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) and benzo[a]pyrene (BaP) was studied using protocols in which these two tobacco smoke carcinogens were given individually or in combination. Groups of female A/J mice were treated by either intragastric gavage (i.g.) or by intraperitoneal injection (i.p.) with various doses of NNK and/or BaP for 8 consecutive weeks. The mice were killed either 9 or 19 weeks later and tumors of the lung and forestomach were counted. The i.g. route of administration proved to be more satisfactory than i.p. administration, because it avoided complications due to tumor formation at the injection site and associated mortality. A dose-response relationship for lung tumor induction by i.g. administration of NNK and BaP in combination was established in the mice killed 9 or 19 weeks after completion of carcinogen treatment. The highest total doses of NNK and BaP (a total of 24 mumol of each) induced more lung tumors than would have been expected by extrapolation from the lower doses. Comparisons of NNK and BaP given individually showed that BaP was more tumorigenic to the lung than NNK when given by the i.g. route; i.p. administrations of BaP were complicated by local tumor formation and mortality. The most favorable dosing regimen of NNK and BaP for evaluation of chemopreventive agents appears to be a total dose of 24 mumol of each, administered in eight weekly subdoses i.g., with sacrifice 9 weeks after completion of dosing. This regimen induced 10.5 +/- 4.4 lung adenomas/mouse. A combination of benzyl isothiocyanate and phenethyl isothiocyanate, given 2 h prior to each gavage of NNK and BaP, was found to be an effective inhibitor of lung tumor formation, reducing the tumor multiplicity to 5.9 +/- 5.7 lung adenomas/mouse (P < 0.001) and completely inhibiting forestomach tumor development. The results of this study provide a convenient model for assessing the efficacy of chemopreventive agents against lung cancer induction by tobacco smoke carcinogens. PMID- 8001226 TI - Involvement of cytochrome P4503A in catalysis of tamoxifen activation and covalent binding to rat and human liver microsomes. AB - Tamoxifen is the major therapeutic agent for the treatment of hormone-dependent breast cancer. Tamoxifen treatment appears to be associated with an increased incidence of endometrial carcinoma in humans and hepatocellular carcinoma in rats. These carcinogenic effects of tamoxifen might be induced by the formation of a tamoxifen reactive intermediate that binds covalently to macromolecules. Liver microsomal cytochrome P450s (CYPs) catalyze the metabolism of tamoxifen, forming a reactive intermediate that binds irreversibly to microsomal proteins, primarily to a 54 kDa protein (Mani, C. and Kupfer, D., Cancer Res., 51, 6052 6058, 1991). The current study identifies the P450 enzymes that catalyze the activation of tamoxifen to a reactive intermediate in rats and humans. Among the species examined, rats, chickens and humans demonstrate low tamoxifen binding activity, ranging from 0.1 to 0.4 nmol bound/mg protein/h. In contrast, hamsters and mice exhibit high binding, 1.2 and 1.6 nmol/mg protein/h respectively. Treatment of male rats with phenobarbital or pregnenolone-16 alpha-carbonitrile (PCN) markedly elevated the binding of tamoxifen to liver microsomal proteins. Methylcholanthrene treatment had no effect on binding. These findings suggested the involvement of CYP3A in catalysis of the covalent binding. Alternate substrates of CYP3A, cortisol and erythromycin, inhibited tamoxifen binding in liver microsomes from PCN- and phenobarbital-treated rats. Treatment of rats with troleandomycin (TAO), an inducer of CYP3A, followed by the dissociation of the TAO-CYP3A complex, elevated the covalent binding to liver microsomes approximately 3-fold. Antibodies against rat CYP3A1 strongly inhibited tamoxifen binding to liver microsomes from PCN- and phenobarbital-treated rats, whereas the antibodies anti-CYP2B1/2B2 did not inhibit binding. In humans, tamoxifen binding was inhibited by the anti-rat CYP3A1 IgG and also by alternate substrates of CYP3A. These results indicate that the activation of tamoxifen to a reactive intermediate by rat and human liver microsomes is principally catalyzed by CYP3A enzymes. PMID- 8001228 TI - Dietary energy restriction and fat modulation of protein kinase C isoenzymes and phorbol ester binding in Sencar mouse epidermis. AB - The purpose of our research is to understand the biochemical basis for dietary enhancement of phorbol ester induced tumor promotion in mice fed high-fat (HF) diet, and the inhibition of promotion in mice fed diets restricted in energy from fat and carbohydrate (ER). The present study assessed the presence of protein kinase C (PKC) isoenzymes in the Sencar mouse epidermis by Western blot and determined the influence of diet on the isoenzymes found. Mice were fed control, HF (24.5% corn oil) or ER (60% of control energy) diets for 6-29 weeks. Our initial studies assessed the immunoreactive levels of PKC alpha, beta, gamma, delta, epsilon and zeta and PKC alpha beta gamma using an antibody to a shared epitope. We detected PKC alpha, epsilon, delta and zeta in sufficient quantity for dietary studies. Dietary fat and energy did not significantly modify the presence of PKC epsilon or delta. We observed a 30% and 40% reduction in PKC alpha in comparison with control diet in cytosolic and particulate fractions respectively, from mice pre-fed ER diet. Reductions of 72% and 82% in cytosolic and particulate PKC were observed respectively with the alpha beta gamma antibody. ER diet reduced the overall amount of PKC zeta in cytosol and particulate by 42% and 59% respectively, with the cytosolic reduction being greater in mice pre-fed the restricted diets for 21-29 weeks. HF diet did not modify the protein levels of the PKC isoenzymes studied. The level of phorbol 12,13-dibutyrate binding to epidermal cells was assessed to determine if the reduction in PKC protein in the epidermis of ER mice would result in altered phorbol binding. Phorbol binding in cells isolated from mice fed ER diet was reduced in mice pre-fed the ER diet for 20-22 weeks in comparison with binding to cells from mice fed control diet. These results suggest that ER diet reduces specific PKC isoenzymes and the binding of phorbol esters in epidermis of mice. These observations may account for the inhibition of phorbol ester promotion of skin tumors in ER mice. PMID- 8001229 TI - Interindividual variation in the isomerization of 4-hydroxytamoxifen by human liver microsomes: involvement of cytochromes P450. AB - Tamoxifen and its metabolite 4-hydroxytamoxifen can both exist as geometrical isomers. Trans-tamoxifen is an oestrogen receptor antagonist and is used for the treatment of breast cancer. Trans-4-hydroxytamoxifen is 100 times more anti oestrogenic than trans-tamoxifen. The cis isomers of tamoxifen and 4 hydroxytamoxifen are oestrogenic and weakly anti-oestrogenic or oestrogenic respectively. Both isomers of 4-hydroxytamoxifen have been detected in breast tumours of patients treated with trans-tamoxifen and it has been proposed that enzymatic isomerization of 4-hydroxytamoxifen occurs in vivo, resulting in resistance to tamoxifen therapy. We have investigated the isomerization of 4 hydroxytamoxifen by human liver microsomes and whether it is mediated by cytochromes P450. Microsomes from five of the 12 livers examined catalysed the interconversion of trans- and cis-4-hydroxytamoxifen (0.52 microM) when incubated for 40 min with an NADPH-generating system. Between 51 and 64% conversion of trans-4-hydroxytamoxifen was observed. Cis-4-hydroxytamoxifen was also converted to trans-4-hydroxytamoxifen (range 22-27%). Incubations with control, heat treated microsomes resulted in approximately 1% isomerization of trans-4 hydroxytamoxifen. The extent of isomerization of trans- to cis-4-hydroxytamoxifen observed in microsomes from the other seven livers (range 2-8%) did not greatly exceed that seen in heat-inactivated microsomes. Enzymatic isomerization required NADPH and was inhibited by SKF 525A and ketoconazole, indicating the involvement of cytochromes P450. Enzymatic isomerization of trans-tamoxifen and trans droloxifene (the 3-hydroxy synthetic analogue of tamoxifen) was not observed. These findings may have implications for the safe and effective use of tamoxifen. PMID- 8001230 TI - Differentiation of oval cells into duct-like cells in preneoplastic liver of rats placed on a choline-deficient diet supplemented with ethionine. AB - Feeding male Wistar rats a choline-deficient diet containing 0.07% DL-ethionine (CDE diet) for up to 5 weeks results in the production of two distinct non parenchymal cell populations, oval and duct-like cells. These cells can undergo replication and display different patterns of expression of glutathione S transferases (GSTs) and pyruvate kinases (PKs). Oval cells were first detected around the periportal region after 1 week of CDE treatment and infiltrated the parenchyma after 2 weeks. Duct-like structures first appeared as isolated ducts in the parenchymal region at 2 weeks and were easily detected after 2.5 weeks. These duct-like structures differed from the bile ducts which reside in the portal region. Large concentrations of duct-like structures in cyst-like clusters were detected after 5 weeks. Enlargement of these structures from single ducts to clusters of up to 20 ducts was observed over 3-5 weeks of CDE treatment. The number of cells forming a duct increased from 5 to 30 cells. We established a double immunocytochemical staining technique to characterize the oval and duct like cells for their expression of GSTs and PKs. pi GST and M2-PK, which are fetal hepatocytes isoenzymes, are present in virtually all the oval and duct-like cells. Most of the oval cells are devoid of the adult hepatocytes markers, alpha GST, mu GST and L-PK. There are two sub-populations of duct-like cells, one which expresses only fetal markers and the other which co-expresses the adult and fetal isoenzymes. Hence, oval cells display characteristics of fetal hepatocytes and some duct-like cells appear more mature than oval cells. Using a combination of double immunocytochemical and [3H]thymidine labelling techniques we have established that oval cells differentiate into duct-like cells. PMID- 8001231 TI - DNA adduct levels of 2-amino-1-methyl-6-phenylimidazo-[4,5-b]pyridine (PhIP) in tissues of cynomolgus monkeys after single or multiple dosing. AB - DNA adducts of 2-amino-1-methyl-6-phenylimidazo[4,5-b]-pyridine (PhIP), a heterocyclic amine derived from cooked meat, were measured by the 32P postlabeling method in tissues of cynomolgus monkeys given PhIP. Monkeys received either a single dose of PhIP (20 mg/kg orally) or nine daily doses of PhIP (20 mg/kg orally, days 1-5 and 8-11) and tissue samples were obtained 24 h after the last dose. Over 28 different tissues were examined for PhIP-DNA adducts. Adducts were detected in all tissues examined except the fat and bone marrow. After a single dose, adduct levels (mean value/10(7) nucleotides, n = 2 monkeys) were highest in the liver (2.1), followed by the lung (1.7), gall bladder (1.7) and pancreas (0.9). Low adduct levels were detected in the brain and aorta (0.06 and 0.02 respectively). Following multiple doses of PhIP, adduct levels (mean value/10(7) nucleotides +/- SE, n = 3 monkeys) were highest in the heart (5.7 +/- 2.0) followed by the liver (3.8 +/- 0.8), submandibular gland (2.7 +/- 1.8) and pancreas (2.2 +/- 0.5). Comparison of the adduct levels after a single dose with those found after multiple doses indicates that accumulation of PhIP-DNA adducts occurred in certain tissues. Adduct levels in liver, pancreas, kidney, small intestine and colon increased about 1.5- to 2.4-fold. PhIP-DNA adduct levels in submandibular gland and brain increased 4- to 5-fold. Adduct levels in heart increased 10-fold and levels in the aorta increased 31-fold. Adducts in white blood cell DNA increased with daily dosing for 9 days. No apparent changes in adduct levels were seen in the lung, stomach, bladder, muscle and spleen. The wide distribution of PhIP-DNA adducts and their presence in white blood cells suggests that there is transport of reactive metabolites from the liver to extrahepatic tissues. The relatively high adduct levels in the gall bladder in comparison with the liver suggests biliary excretion and possible reabsorption of reactive metabolites. The presence of DNA adducts in tissues implicates PhIP as a potential carcinogen in non-human primates. The possibility that PhIP-DNA adducts in tissues such as the heart and aorta may have toxicological consequences is discussed. PMID- 8001232 TI - Transforming growth factor-beta receptors type I, II and III in phenobarbital promoted rat liver tumors. AB - Rat liver tumors initiated with N-nitrosodiethylamine (DEN) followed by promotion with phenobarbital (PB) were examined for expression of transforming growth factor-beta (TGF beta) type I, II and III receptors. RNase protection and TGF beta 1 affinity labeling assays were used to determine TGF beta receptor steady state mRNA and protein levels, respectively. We have demonstrated that all three TGF beta receptors are expressed in both normal and malignant hepatic tissues. Long-term PB administration did not alter TGF beta receptor mRNA or protein levels in normal liver. However, type I, II and III TGF beta receptor mRNA and protein levels were decreased by approximately 50% in the DEN-initiated/PB promoted liver tumors as compared to the receptor levels in normal liver tissue surrounding the tumors. In contrast, TGF beta receptor mRNA and protein levels were unchanged in liver tumors initiated with DEN but not PB-promoted. These data demonstrate that PB promotes the formation of a tumor phenotype that is characterized by a significantly reduced number of TGF beta type I, II and III receptors. This suggests that the down-regulation of TGF beta receptors in PB promoted hepatic tumors may provide a selective growth advantage to the tumor cells by reducing the ability of TGF beta to inhibit their growth. PMID- 8001233 TI - Loss of heterozygosity of the human cytosolic glutathione peroxidase I gene in lung cancer. AB - The consistent deletion of 3p21 in lung cancer has led to intensive efforts to identify a lung tumor suppressor gene at this locus. We recently mapped the gene for the selenium-dependent drug-detoxifying enzyme glutathione peroxidase 1 (GPX1) to this location by in situ hybridization. We developed a polymerase chain reaction-based assay which demonstrated the existence of three GPX1 alleles characterized by the number of alanines in a polyalanine coding sequence in exon 1. These three alleles produced a heterozygote frequency of 70% in two separate populations: normal tissue DNA taken from Centre d'Etude du Polmorphisme Humain (CEPH) parents and normal tissue taken from cancer patients. In contrast, 10 heterozygote tumors were detected out of 64 lung cancer specimens. Linkage analysis of GPX1 to Genethon 3p markers in CEPH pedigrees demonstrated that GPX1 was located between the two microsatellite markers believed to flank the lung cancer deletion site. Nucleotide sequence analysis of GPX1 alleles did not reveal any mutations of this gene in lung tumors. However, sequence analysis did reveal that the three GPX1 alleles were characterized by three nucleotide substitutions in addition to the polyalanine polymorphism, including a substitution at codon 198 which results in either a proline or leucine at that position. Therefore, the different GPX1 alleles encode structurally different hGPx1 subunits. In addition, analysis of allele frequency suggests that the GPX1*ALA7 allele may occur less frequently in tumors with 3p21 deletions. PMID- 8001234 TI - Chemopreventive effects of the aromatase inhibitors vorozole (R-83842) and 4 hydroxyandrostenedione in the methylnitrosourea (MNU)-induced mammary tumor model in Sprague-Dawley rats. AB - The chemopreventive activity of the aromatase inhibitors vorozole and 4 hydroxyandrostenedione were determined in the methylnitrosourea (MNU)-induced model of rat mammary tumorigenesis. Vorozole (5 and 2.5 mg/kg body wt) and 4 hydroxyandrostenedione (15 and 6 mg/rat) were administered daily (by gavage) to virgin female Sprague-Dawley rats starting at an age of 43 days. Seven days later animals were given a single dose of MNU. Following treatment with MNU, animals continued to be treated with vorozole and 4-hydroxyandrostenedione daily until the end of the experiment (100 days post MNU treatment). Vorozole at either dose proved to be a profound inhibitor of MNU-induced mammary tumors. Vorozole decreased tumor incidence from 100% to 10%, while simultaneously decreasing tumor multiplicity from 5 tumors per animal to 0.1 tumors per animal. This chemopreventive effect was accompanied by significant increases in body weight gain in the animals treated with vorozole when compared with control rats. In contrast, neither dose of 4-hydroxyandrostenedione had any effect on tumor incidence and only the higher dose slightly decreased tumor multiplicity. PMID- 8001235 TI - Expression of N-acetyltransferase (NAT) in cultured human uroepithelial cells. AB - To determine which of the N-acetyltransferase (NAT) alleles [monomorphic (NAT1) or polymorphic (NAT2)] are expressed in the target cells for arylamine carcinogenesis, namely normal human uroepithelial cells, cDNA was prepared from cellular RNA and amplified by polymerase chain reaction (PCR), using upstream primer 1 comprising the 5' end (nt 47-68) and either downstream primers 2 (nt 908 889) or 3 (nt 953-931) corresponding with the 3' end. With primers 1 and 2, selective for NAT1, a characteristic 861 bp DNA fragment was obtained, whereas with primers 1 and 3, selective for NAT2, a characteristic 907 bp fragment was formed. Similarly, the PCR-amplified cDNA products from the SV40-immortalized human uroepithelial cell line were also found to contain both NAT1 and NAT2. Restriction fragment length polymorphism (RFLP) analysis with HincII (digesting NAT2 to produce 659 bp and 248 bp fragments) and HindIII (digesting NAT1 to produce a 786 bp fragment) further confirmed the authenticity of the NAT alleles. Furthermore, the NAT genotypes of 38 individuals were determined by PCR amplification of lymphocyte DNA and subsequent RFLP analysis using TaqI, KpnI and BamHI. The genotypes were compared to their in vivo acetylator phenotypes which were determined by measuring 5-acetylamino-6-formylamino-3-methyluracil and 1 methylxanthine in urine following administration of caffeine. A good correlation between the genotype and phenotype was obtained in the study population and the frequency of NAT2 allele distribution was M1 > wild-type > M2 > M3. These results suggest that susceptibility to arylamine-induced bladder cancer might be influenced by both hepatic and bladder NAT and that the NAT genotype might be a useful biomarker for screening high risk individuals for bladder cancer resulting from exposure to arylamines. PMID- 8001236 TI - Regulation of c-jun by lung carcinogens in Clara cells of hamsters. AB - In vitro differentiated hamster Clara cells were used to study the effects of lung carcinogens on the regulation of the c-jun oncogene. Northern blot analysis revealed a decrease in the expression of jun transcripts 24 h following the exposure of Clara cells to the direct acting forms of benzo[a]pyrene (BPDE*) or 5 methylchrysene (5MeCDE). To determine whether this decrease was mediated at the transcriptional level, we have used CAT reporter constructs driven by nested deletions of the 5' non-coding regulatory region of the c-jun oncogene. While BPDE was capable of activating certain regulatory domains of the c-jun promoter, this activation was not observed with either 5MeCDE or the less active lung carcinogens BADE or 6MeCDE. Analysis of enhancer elements identified the SP1 target site as a strong silencer after BPDE treatment. While positive regulatory element(s) mediating activation of c-jun by BPDE were localized within the promoter region up to -1639, further upstream sequences reduced this transcriptional activation. Thus, when the complete promoter region, up to -4500, was tested, no transcriptional activation was noted following BPDE treatment. These observations suggest that the regulation of c-jun in Clara cells exposed to potent lung carcinogens is mediated at the post-transcriptional level, possibly by reducing the stability and, in turn, the half life of c-jun mRNA. Overall, in contrast to the response of c-jun to numerous carcinogens and stress inducing agents noted in various other cell systems, our findings suggest the existence of a tissue-specific regulatory response for c-jun. PMID- 8001237 TI - Loss of mouse epidermal protein kinase C isozyme activities following treatment with phorbol ester and non-phorbol ester tumor promoters. AB - The present study has examined changes in activities and levels of four protein kinase C (PKC) isozymes (PKC alpha, PKC beta, PKC gamma and PKC delta) detectable in mouse epidermal preparations following both single and multiple treatments with 12-O-tetradecanoylphorbol-13-acetate (TPA). In addition, PKC epsilon and PKC eta protein levels were monitored by immunoblotting following TPA application. Finally, PKC isozyme activity profiles were also examined in epidermal preparations from mice treated with single applications of two non-phorbol ester tumor promoters: chrysarobin (CHRY) and okadaic acid (OA). Fifteen minutes following topical treatment with a tumor promoting dose of TPA (3.4 nmol), the activities of PKC beta and PKC gamma decreased in the epidermal cytosol to 30% and 50% of control values, respectively, while these activities were increased in the epidermal particulate fraction by approximately 50%. PKC delta activity, found predominantly in the particulate fraction of control epidermis, was greatly diminished in both subcellular fractions at 15 min while PKC alpha activity was translocated approximately 20% from cytosol to particulate fraction. Significant reductions in all four detectable PKC isozyme activities in both particulate and cytosol fractions were observed 48 h after a single treatment with TPA, although particulate PKC alpha activity appeared to be less affected at this point in time compared to the other PKC isozymes. Immunoblotting analyses of PKC isozyme protein levels after TPA treatment followed the changes in activity for cytosolic PKC alpha, PKC beta and PKC gamma. However, particulate PKC delta and PKC epsilon protein levels remained relatively unchanged while particulate PKC eta protein levels were significantly down-regulated after a single TPA treatment. Multiple topical treatments (twice-weekly for 2 weeks) with TPA produced a pattern of loss followed by only partial recovery of total PKC activity. Furthermore, all four PKC isozyme activities examined by hydroxylapatite (HA) chromatography were significantly reduced, including PKC alpha, after four applications of TPA. Cytosolic PKC alpha, PKC beta and PKC gamma protein levels as determined by immunoblotting again followed the activity profiles; particulate PKC eta protein levels were significantly reduced, whereas particulate PKC delta and PKC epsilon levels again appeared relatively unchanged. Fifteen minutes after topical application of 220 nmol CHRY, an approximately 25% decrease in particulate associated with PKC alpha activity was observed while particulate activities associated with PKC beta, PKC gamma and PKC delta were unaffected by CHRY at this time point.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8001238 TI - Tissue-specific mutational spectra of 2-amino-3,4-dimethylimidazo[4,5-f]quinoline in the liver and bone marrow of lacI transgenic mice. AB - 2-Amino-3,4-dimethylimidazo[4,5-f]quinoline (MeIQ) is a food-borne heterocyclic amine, so clarification of its mutational spectrum is important for evaluation of its carcinogenic risk to humans. The mutational spectrum of MeIQ was investigated in the liver and bone marrow of transgenic mice carrying the lacI gene. By PCR- single-strand conformation polymorphism analysis and sequencing of the lacI gene, 81 and 61 mutations were identified in 80 and 59 mutants obtained from the liver and bone marrow respectively of three transgenic mice given food containing 300 p.p.m. MeIQ. In the liver, G-->T transversions were the most frequent, accounting for 46% of the total mutations, followed by G-->A transitions (25%). In the bone marrow, four types of mutations, G-->T transversions, G-->A transitions, complex mutations and one base deletions, each accounted for 21-23% of the total mutations. Of the total mutations, 10% were found at nucleotide 92 in the liver and at nucleotide 222 in the bone marrow. Analysis of 27 and 13 mutants from the liver and bone marrow respectively of control mice showed frequent G-->A transitions at CpG sites. These findings suggest a tissue-specific mechanism of mutagenesis. PMID- 8001239 TI - Glutathione can rescue the inhibitory effects of nickel on DNA ligation and repair synthesis. AB - The purpose of this investigation was to explore the reason why nickel chloride enhances the cytotoxicity and genotoxicity of ultraviolet (UV) light, but not that of methyl methanesulfonate (MMS) in Chinese hamster ovary cells. The cellular glutathione content was increased by treatment with MMS or nickel, but not with UV. Post-treatment with nickel synergistically raised the cellular glutathione content in MMS-treated cells; this phenomenon was not observed in UV irradiated cells. Preventing cellular glutathione induction by buthionine sulfoximine increased the cytotoxicity, the frequency of sister chromatid exchange and prolonged the cell cycle in cells treated with nickel or MMS plus nickel. Pretreatment with N-acetylcysteine, a glutathione precursor, increased the clonogenic survival of cells treated with UV plus nickel. In vitro assays indicated that nickel could inhibit oligonucleotide ligation and the repair synthesis of UV- or MMS-treated plasmids and glutathione could relieve nickel inhibition. These results suggest that the enhancement by nickel of UV cytotoxicity and genotoxicity may be due to its inhibition of DNA repair, whereas treating cells with MMS plus nickel increased cellular glutathione levels, which may help in neutralizing the toxicity of nickel. The results also suggest that the activity of gamma-glutamylcysteine synthetase, the rate-limiting enzyme in glutathione biosynthesis, may be increased by treatment with MMS, nickel and more so with MMS plus nickel. PMID- 8001240 TI - Induction of free radicals and tumors in the kidneys of Wistar rats by ferric ethylenediamine-N,N'-diacetate. AB - An iron chelate, ferric ethylenediamine-N,N'-diacetate [Fe(III)-EDDA], was found to produce hydroxyl radicals with hydrogen peroxide, as determined by both a deoxyribose degradation test and electron spin resonance. Hydroxyl radical production was inhibited not only by adding hydroxyl radical scavengers and catalase, but also by adding superoxide dismutase to the reaction mixture, suggesting that superoxide anion may be involved in the hydroxyl radical production. A single injection of Fe(III)-EDDA (10 mg Fe/kg body wt) to Wistar rats induced thiobarbituric acid reactivity in the kidneys and liver. Repeated injections of Fe(III)-EDDA (10 mg Fe/kg body wt, twice weekly for 3 months) induced a 40% incidence of renal tumors, including renal adenocarcinoma and renal adenoma, 1 year later. These results suggest that Fe(III)-EDDA is an effective free radical producer in vitro and in vivo and that it may be useful in preparing animal models related to iron-dependent free radical damage. The results support our hypothesis that endogenous or exogenous iron, complexed with certain kinds of chelators, promotes free radical-dependent tissue damage and ultimately leads to carcinogenesis in the affected tissue. PMID- 8001241 TI - Phorbol ester-induced leukotriene biosynthesis and tumor promotion in mouse epidermis. AB - In mouse skin in vivo the irritant and hyperplasiogenic tumor promoter 12-O tetradecanoylphorbol-13-acetate (TPA) strongly increased the epidermal content of the cysteinyl leukotrienes LTC4, LTD4 and LTE4, but not of leukotriene LTB4. This effect was completely suppressed by the selective leukotriene biosynthesis inhibitor MK-886. Intragastric administration of MK-886 prevented phorbol ester induced ear edema, but not epidermal hyperproliferation and tumor promotion. These data indicate that leukotrienes are involved in the pro-inflammatory effects of the phorbol ester, whereas its hyperproliferative and tumor-promoting activities do not depend on 5-lipoxygenase-catalyzed leukotriene formation. This action differs from several non-selective inhibitors of lipoxygenases that were found to inhibit tumor promotion in initiated mouse skin. PMID- 8001242 TI - Comparison of TLC- and HPLC-32P-postlabelling assay for cisplatin-DNA adducts. AB - Calf thymus DNA, treated with the antitumour agent cis diamminedichloroplatinum(II) (cisplatin), was enzymatically digested with deoxyribonuclease I, snake venom phosphodiesterase and prostatic acid phosphatase. As a result the adducts were released with an unmodified nucleotide at their 5'-side. The adducts were postlabelled with [gamma-32P]ATP and separated by thin-layer chromatography (TLC) and HPLC with on-line detection of 32P. One of the standards, platinated d(TGG), could be analysed with a recovery of 31% with both the TLC and the HPLC separation systems, when the amount of adduct was between 0.5 and 100 fmol. In the case of platinated DNA the linear part of the concentration curve was from 100 fmol down to the lowest amount of adducts measured, 3.2 fmol, with the TLC system and between 8 and 40 fmol with the HPLC system. The recoveries of the adducts were 28% and 16% respectively. PMID- 8001243 TI - Aryl hydrocarbon (Ah) receptor-independent induction of Cyp1a2 gene expression by acenaphthylene and related compounds in B6C3F1 mice. AB - Treatment of B6C3F1 mice with acenaphthylene, acenaphthene, fluorene, phenanthrene, anthracene and dibenzofuran resulted in induction of hepatic microsomal methoxyresorufin O-deethylase (MROD) activity. Acenaphthylene was the most potent inducer of MROD, a Cyp1a2-dependent activity, and was utilized as a prototypical inducer for this group of tricyclic hydrocarbons. Acenaphthylene (300 mg/kg) caused a > 80-fold induction of hepatic microsomal MROD activity; no induction was observed in kidney or lung. Analysis of induced hepatic microsomes with antibodies to Cyp1a1 and Cyp1a2 showed that acenaphthylene induced immunoreactive Cyp1a2 but not Cyp1a1 proteins and subsequent mRNA analysis confirmed with a cDNA probe for Cyp1a1 and Cyp1a2 that acenaphthylene induced Cyp1a2 but not Cyp1a1 mRNA. Results from nuclear run-on experiments using hepatic nuclei showed that acenaphthylene caused an approximately 4-fold increase in the rate of Cyp1a2 gene transcription in B6C3F1 mice. Results of competitive binding studies indicated that the tricyclic hydrocarbons did not competitively displace [3H]2,3,7,8-tetrachlorodibenzo-p-dioxin or [3H]benzo[a]pyrene from the mouse hepatic cytosolic aryl hydrocarbon (Ah) receptor or 4S carcinogen binding protein respectively. The data indicate that acenaphthylene and related tricyclic hydrocarbons induce Cyp1a2 gene expression in B6C3F1 mice via an Ah receptor independent pathway. Thus, tricyclic hydrocarbons induce Cyp1a2 without the co induction of Cyp1a1 and therefore these relatively non-toxic compounds can be used to further probe the role of Cyp1a2 in the metabolism and metabolic activation of diverse chemical carcinogens. PMID- 8001244 TI - Theta class glutathione S-transferase GSTT1 genotypes and susceptibility to cervical neoplasia: interactions with GSTM1, CYP2D6 and smoking. AB - The factors that determine progression of cervical intra-epithelial neoplasia (CIN) to squamous cell carcinoma (SCC) are unknown. Cigarette smoking is a risk factor, suggesting polymorphism at loci that encode carcinogen-metabolizing enzymes such as glutathione S-transferase (GSTT1, GSTM1) and cytochrome P450 (CYP2D6) may determine susceptibility to these cancers. We have studied the frequency of the null genotype at the theta class GSTT1 locus in women with low grade CIN, high-grade CIN and SCC. The control group comprised women with normal cervical pathology suffering menorrhagia. We found the frequency of GSTT1 null in the control and case groups was not significantly different, though frequency distributions of combinations of the genotype with smoking in mutually exclusive groups in the high-grade CIN group and the other case groups were significantly different. Interactive effects of GSTT1 null with the GSTM1 null and CYP2D6 EM genotypes, and cigarette smoking were also studied by comparing the multinomial frequency distributions of these factors over mutually exclusive categories. These showed no significant differences between the controls and SCC or low-grade CIN. Frequency distributions in high-grade CIN, however, were significantly different to the controls, and both SCC and low-grade CIN; frequency distributions of GSTT1 null with smoking and CYP2D6 EM, individually and in combination, were significantly different. However, inspection of our data does not indicate that GSTT1 null is a major factor mediating risk. Thus, comparison of chi 2 values for the differences between frequency distributions in high-grade CIN and other groups shows that values for combinations of GSTT1 null with other factors are lower than those for equivalent combinations with smoking and CYP2D6 EM. Interestingly, the combination GSTT1 null/GSTM1 null did not appear to influence susceptibility to CIN or SCC. PMID- 8001245 TI - Effect of the peroxisome proliferators ciprofibrate and perfluorodecanoic acid on hepatic cell proliferation and toxicity in Sprague-Dawley rats. AB - The objective of this study was to compare the effects of perfluorodecanoic acid (PFDA) and ciprofibrate on the induction of hepatic toxicity and on hepatocellular proliferation in rats. In the first study, rats were first subjected to partial hepatectomy and then injected with [3H]thymidine (20 microCi/injection) at 23, 24, 25, 47, 48 and 49 h afterwards. After a 2 week recovery period, rats were injected with one of four levels of PFDA (0.3, 1.0, 3.0 or 10 mg/kg/injection) in four i.p. doses every 14 days, or were fed 0.01% or 0.003% ciprofibrate. Six days after the last PFDA injection and three days before the animals were killed, an osmotic minipump containing 20 mg/ml 5-bromo-2' deoxyuridine (BrdU) was implanted s.c. for the measurement of DNA synthesis. Peroxisomal fatty acyl-CoA oxidase activity was significantly enhanced in both PFDA and ciprofibrate-treated groups in a dose-dependent manner. Hepatotoxicity, measured as the loss of [3H]thymidine from hepatic DNA, was not significantly affected by any of the treatments. Hepatic DNA synthesis was significantly increased only in rats receiving the highest dose of PFDA. In order to determine the time course of ciprofibrate- and PFDA-induced cell proliferation, we conducted another study with more time points. Rats were fed 0.01% ciprofibrate or were injected every 14 days with 3 or 10 mg PFDA/kg body weight for 10 days, 24 days, 6 weeks, 26 weeks or 54 weeks. Cell proliferation was quantified as in the first study. Ciprofibrate increased cell proliferation at the early but not the later time points, whereas PFDA increased cell proliferation at most times throughout the study. This study demonstrates that PFDA and ciprofibrate do not selectively induce hepatic toxicity and that their effects on cell proliferation do not correlate with their carcinogenic or promoting activities. PMID- 8001246 TI - A protective effect of chromosome 11 against DNA damage by TPA-activated neutrophils but not TPA acting alone. AB - Evidence from animal models suggests that 12-O-tetrade-canoylphorbol-13-acetate (TPA) is capable of inducing genetic damage within a tissue, although the mechanism underlying this response is unknown. A favoured hypothesis is that the TPA is acting either by stimulating cells in the tissue directly to generate DNA damaging agents or by recruiting inflammatory cells to the tissue and stimulating them to release such agents. These agents include reactive oxygen species, such as hydrogen peroxide and superoxide anion, as well as products generated during lipid peroxidation and arachidonic acid metabolism. It is not known whether significant alterations occur in the sensitivity of cells to TPA during the process of tumourigenesis. In this paper the capacity of TPA to induce chromosomal breakage (measured by micronuclei induction) was found to be elevated in bladder tumour cell lines compared to two normal cultures, a primary epithelial culture and a fibroblast culture. This effect was observed when cells were exposed to TPA directly or co-cultured with TPA-activated neutrophils isolated from human blood. In addition, we present evidence that loci on chromosome 11 may be involved in altering the response of cells to TPA. When chromosome 11 was inserted into a bladder tumour cell line, a reduction in sensitivity to TPA-activated neutrophils was observed. The chromosome insert did not protect against damage induced by direct treatment with TPA alone. In another scenario, fibroblasts from a patient with ataxia telangiectasia, a syndrome localized to chromosome 11, were shown to have an elevated sensitivity to the chromosome damaging action of TPA-activated neutrophils, but not to TPA alone. These results suggest that some of the alterations occurring in a tissue during tumourigenesis could have a significant impact on the responsiveness of cells to genetic damage by TPA. They also suggest that the damage induced by TPA in a cell may be different if a neutrophil is present. PMID- 8001247 TI - Human CYP2A6 activation of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK): mutational specificity in the gpt gene of AS52 cells. AB - The tobacco-specific nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1- butanone (NNK) is a potential human carcinogen that is known to be metabolized to DNA reactive intermediates by the cytochromes P450. We have examined the nature of NNK's DNA damaging effects in a mammalian cell system expressing a specific human cytochrome P450 (2A6) and containing a target gene for mutagenesis. Human CYP2A6, which is known to activate NNK to a mutagen, was lipofected via a retroviral vector into the Chinese hamster ovary AS52 cell line, which contains the bacterial gpt gene and can be mutated to 6-thioguanine resistance. AS52 cells expressed negligible CYP2A6-specific coumarin 7-hydroxylase activity (0.7 pmol/mg protein/min), while a CYP2A6 transfected clone (AS52-E8) expressed 30 pmol/mg protein/min. Both cell lines were equally sensitive to the cytotoxic and mutagenic effects of the direct-acting mutagen ethylmethanesulfonate; however, only the AS52-E8 cells exhibited a dose-dependent increase in cytotoxicity and mutant frequency upon treatment with NNK. At the highest NNK dose (1200 micrograms/ml), the mutant frequency in AS52-E8 cells was 14-fold (339 x 10(-6)) greater than the spontaneous frequency of 24 x 10(-6). Ninty-eight mutant clones were isolated following NNK treatment. Based on PCR analysis, 21 clones contained deletions/rearrangements and 77 were putative point mutants. Sequencing potential point mutants showed that 81% contained G:C to A:T transitions. Four of six G:C to A:T hotspots were at the second G of the GGT motif, which is the motif and major mutation found in codon 12 of Ki-ras from NNK-induced lung tumors in strain A mice. Since NNK may be metabolized via different pathways to pyridyloxobutylate or methylate DNA, the data suggest that methylation damage causes the major mutagenic events in AS52-E8 cells when NNK is activated by human CYP2A6. PMID- 8001248 TI - Transformation of human epidermal keratinocytes with fission neutrons. AB - The biological effects of exposures to high LET radiations have particular relevance to radiation protection and risk assessment. Since most cancers are of epithelial origin, it is important to obtain a better understanding of radiation induced oncogenic transformation in this cell type. Accordingly we have initiated studies to determine whether immortalized human epidermal keratinocytes (RHEK) can be transformed with high LET radiations. Exponentially growing RHEK cells were treated with single doses (1, 10, 25, 50 and 100 cGy) of 0.85 MeV fission neutrons from the Janus reactor. Neutron exposure led to the development of morphologically altered cells and foci formation after 6 weeks at confluence. These transformed cultures grew with an increased saturation density, exhibited anchorage-independent growth and formed tumors in athymic mice. Single-strand conformational polymorphism analysis and DNA sequencing demonstrated the absence of point mutations in codons 12/13 and 61 in the Ha-ras, Ki-ras, or N-ras genes and exons 4-9 of the p53 tumor suppressor gene. These studies demonstrate that high LET radiations (fission neutrons) can transform immortalized human epithelial cells to a malignant phenotype that does not appear to involve mutations in either the cellular p53 or ras genes. PMID- 8001250 TI - Activity of triphenylselenonium chloride in mammary cancer prevention. AB - The present study was designed to evaluate the tolerance and cancer chemopreventive activity of triphenylselenonium chloride in female Sprague-Dawley rats. No information is available in the literature on the anticarcinogenic efficacy of a lipophilic cationic selenium compound as exemplified by the triphenylselenonium ion. A short-term preliminary study indicated that it was well tolerated via the dietary route. Supplementation at levels up to 200 p.p.m. Se did not produce any apparent adverse effect in the animals. In the dimethylbenzanthracene mammary cancer model, a level of 30 p.p.m. Se in the diet reduced the total tumor yield by approximately 70% when treatment was applied during either the initiation phase or the post-initiation phase. In the MNU mammary cancer model, the inhibitory response was expressed only during the post initiation phase. These findings suggest that the triphenylselenonium ion may have multiple modes of action in suppressing the development of neoplasia. Tissue analysis confirmed that there was minimal accumulation of total selenium until the level of supplementation reached 100 p.p.m. Se or above. Our study therefore convincingly demonstrates that triphenylselenonium chloride fits the criteria of an effective and desirable anticancer agent with a distinct separation between the chemopreventive dose range and the toxic dose range. PMID- 8001249 TI - Woodchuck hepatitis virus surface antigen induces nitric oxide synthesis in hepatocytes: possible role in hepatocarcinogenesis. AB - Woodchuck hepatitis virus surface antigen (WHsAg) stimulated hepatocytes in culture to produce nitric oxide (NO.), as evidenced by the accumulation of nitrite in the medium. NO. synthesis by hepatocytes was positively correlated with WHsAg concentration. WHsAg-induced NO. synthesis was inhibited by NG monomethyl-L-arginine and anti-WHsAg antibody. To our knowledge, this is the first demonstration of an increase in NO. formation by a viral antigen. These data, when considered in the light of the known genotoxicity of NO., raise the possibility that viral hepatitis increases the risk of liver cancer by increasing the production of NO.. Long-term elevated production of NO. free radicals due to stimulation by WHsAg in chronic hepatitis may directly cause reactions with cellular DNA leading to mutagenesis, as well as the formation of hepatocarcinogenic N-nitroso compounds. This provides a new mechanism by which hepatitis B virus infection might hypothetically increase the risk of liver cancer. PMID- 8001251 TI - Detection of N-(deoxyguanosin-8-yl)-2-fluorenamine in DNA of peritoneal serosa and liver after intraperitoneal exposure of rats to N-hydroxy-N-2 fluorenylbenzamide or N-hydroxy-N-2-fluorenylacetamide. AB - DNA adduct formation was examined in rat peritoneal serosa, a tumor target for i.p. administered aqueous suspensions of N-hydroxy-N-2-fluorenylbenzamide (N-OH-2 FBA) and N-hydroxy-N-2-fluorenylacetamide (N-OH-2-FAA), and compared to that in the liver, which is a tumor target for N-OH-2-FAA in the male rat. 32P Postlabeling analyses showed the presence of a single adduct, N-(deoxyguanosin-8 yl)-2-fluorenamine (dG-C8-FA), from activation of both hydroxamic acids by the serosa and liver in vitro and in vivo. The relatively low levels of dG-C8-FA (60 80 fmol/micrograms DNA) from N-OH-2-FBA in vitro were increased 2.7- and 35-fold upon the addition of acetyl coenzyme A (AcCoA) to the serosal cytosol and hepatic cytosol or microsomes respectively. By contrast, addition of AcCoA led to a decrease (approximately 34%) in the high level of dG-C8-FA (4330 fmol/micrograms DNA) from activation of N-OH-2-FAA by hepatic cytosol and did not alter the levels from activation by hepatic microsomes and serosal cytosols (530 and 78.3 fmol/micrograms DNA respectively). These data and the previously reported hydroxamic acid activation enzyme activities in the serosa and liver indicated that the precursor of dG-C8-FA, N-acetoxy-N-2-fluorenamine, was formed from N-OH 2-FAA chiefly via an intramolecular N,O-acetyltransfer and from N-OH-2-FBA via a two-step sequence of N-debenzoylation and AcCoA-dependent O-acetylation. The levels of dG-C8-FA were approximately 2- to 3-fold higher in the serosal DNA (up to 515 and 1012 fmol/micrograms DNA) after one (30 mumol/rat) and ten or eleven (cumulative dose of approximately 275 mumol/rat) injections of N-OH-2-FBA or N-OH 2-FAA than in the hepatic DNA. This correlated with the carcinogenicities of the hydroxamic acids, but was inversely proportional to the rates and extents of their activation in vitro. Multiple injections affected hepatic enzyme activities related to the activation of the hydroxamic acids in that the cytosolic N debenzoylation of N-OH-2-FBA increased (approximately 1.7-fold) whereas N-OH-2 FAA acetyltransferase and sulfotransferase activities decreased. The effect of treatment with N-OH-2-FBA was greater than that with N-OH-2-FAA and was greater on the sulfotransferase activity (approximately 88% decrease). The latter suggested that N-OH-2-FBA, although a poor acceptor for an enzymatic sulfate transfer, may be carcinogenic for the rat liver.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8001252 TI - Flanking base effects on the structural conformation of the (+)-trans-anti benzo[a]pyrene diolepoxide adduct to N2-dG in sequence-defined oligonucleotides. AB - Conformations of the trans adduct of (+)-anti-benzo[a]pyrene -7,8-dihydrodiol 9,10-epoxide (BPDE) to N2-guanine, the major stable DNA adduct of the environmental carcinogen benzo[a]pyrene, were studied as a function of flanking bases in single-stranded and in double-stranded oligonucleotides. Three 11mer oligonucleotides d(CTAT-G1G2G3TATC) were synthesized containing the (+)-trans anti-BPDE adduct at one specific guanine of the GGG sequence (a known mutational hot spot). Polyacrylamide gel electrophoresis of the three single-stranded oligonucleotides showed that the adduct bound to G2 or G3 (5'-flanking base guanine) caused significantly stronger retardation than the same adduct bound to G1 (5'-flanking base thymine). The strength of the carcinogen-base interaction was reflected in the spectroscopic properties of the pyrenyl moiety. Low temperature fluorescence measurements under line-narrowing (FLN) or non-line narrowing (NLN) conditions showed that in single-stranded form the adduct at G2 or G3 (5'-flanking base guanine) adopts a conformation with strong interaction with the bases. This was also observed for the same adduct at the sequence AGA. In contrast, the (+)-trans-anti-BPDE adduct with a 5'-flanking thymine exists in a primarily helix-external conformation. Similar differences were observed in the double-stranded oligonucleotides: the adducts at G2 and G3 were found to exist in similar conformational equilibria, again with significant carcinogen-base interactions, while the adduct at G1 showed a predominantly external conformation. The nature of the 3'-flanking base appeared to have little influence on the conformational equilibrium of the (+)-trans-anti-BPDE-guanine adduct. The results could provide insight into the mutational specificity and flanking base effects observed for (+)-anti-BPDE. PMID- 8001253 TI - Mutagenicity of nitric oxide is not caused by deamination of cytosine or 5 methylcytosine in double-stranded DNA. AB - Several human tumors of diverse histological origin have a high incidence of C:G to T:A transition mutations at methylated CpG sites in tumor suppressor genes. We used a sensitive genetic assay to examine the ability of nitric oxide (NO), a physiological intra- and intercellular messenger molecule, to promote these transitions by deaminating cytosine (C) or methylcytosine (5mC) in double stranded DNA. Exposure of a test double-stranded plasmid containing C or 5mC at the target site to NO in phosphate-buffered solution at pH 7.4 followed by transformation into Escherichia coli ung- strain to avoid repair of U did not result in a significant increase in reversion frequency. In addition, exposure of E. coli transformed with the target plasmid to an NO-releasing spermine-NO complex during log-phase growth did not result in larger numbers of revertants, whereas Salmonella typhimurium strain TA1535 showed a dose-responsive increase in reversion frequency when treated in the same way. We conclude that genotoxicity of NO is not caused by deamination of C or 5mC to U or T, respectively, in double stranded DNA. This is supported by the finding that extracts of TA1535 contained high uracil-DNA glycosylase activity, suggesting that the difference in mutagenesis between the strains is not due to a lack of uracil repair. Therefore, mutational hot-spots seen in human tumor tissues at CpG sites are probably not due to the action of NO at 5mC. PMID- 8001254 TI - Carcinogen-DNA adducts and gene mutation in foundry workers with low-level exposure to polycyclic aromatic hydrocarbons. AB - Carcinogen-DNA adducts and somatic gene mutation at the hypoxanthine guanine phosphoribosyl transferase (HPRT) locus were evaluated in peripheral leukocytes of workers in an iron foundry with exposure to benzo[a]pyrene (B[a]P) and other polycyclic aromatic hydrocarbons (PAHs). During the two year study period, B[a]P exposure declined by approximately 40%, from a maximum of 60 ng/m3 in the first year to < 36 ng/m3 1 year later. A total of 64 persons were sampled in November/December of the two successive study years; 24 of them gave two samples one year apart. The biomarkers included carcinogen-DNA adducts in leukocytes (PAH DNA measured by an immunoassay, aromatic-DNA by the 32P-postlabeling method) and HPRT mutation in lymphocytes. After adjusting for smoking, levels of PAH-DNA, aromatic-DNA and HPRT mutation frequency (Mf) increased with exposure among the 64 workers sampled during the 2 year period (P < or = 0.05). However, the markers showed a differential response to the change in exposure, consistent with their individual biology. For example, among the 24 workers sampled in both years, carcinogen-DNA adducts (which have a half-life on the order of several months) were markedly reduced from the first to the second year (PAH-DNA, 6.2 versus 2.3/10(8); aromatic-DNA, 2.5 versus 1.4/(8); P < 0.01). HPRT Mf (a longer-lived marker) was somewhat less affected by the decline in exposure (1.3 versus 0.8, P < or = 0.05). Moreover, in the second year several long-term workers had low levels of adducts, but elevated HPRT Mf. Thus, PAH-DNA and HPRT Mf were highly correlated in the first year (n = 17; r = 0.67; P < 0.01), but not in the second year or in the two years combined. However, when analysis was restricted to workers with detectable levels of adducts (who included the more highly exposed workers) the correlation was significant between PAH-DNA and HPRT (n = 17; r = 0.65; P = 0.005). In contrast, aromatic-DNA adducts and HPRT were not correlated in either year. These results suggest a molecular link between somatic gene mutation and PAHs; and they highlight the need in such molecular epidemiologic studies to consider the varying lifetimes of the individual markers. PMID- 8001255 TI - Two pathways for chromium(VI)-induced DNA damage in 14 day chick embryos: Cr-DNA binding in liver and 8-oxo-2'-deoxyguanosine in red blood cells. AB - Previous studies have shown that chromium(VI) induced cell-specific types of DNA damage, i.e. DNA cross-links in liver and DNA strand breaks in red blood cells, in 14 day chick embryos. Direct and indirect pathways for chromium(VI)-mediated DNA damage, in the form of Cr-DNA binding and 8-oxo-2'-deoxyguanosine (8-oxo-dG) respectively, were examined in liver and red blood cells of 14 day chick embryos. Levels of hepatic Cr-DNA binding increased in a Cr(VI) dose-dependent manner. Cr DNA binding in red blood cells was 10-fold lower than in liver, although the Cr uptake in red blood cells was only 2-fold lower than in liver. The level of 8-oxo dG formation in red blood cells increased at all Cr(VI) doses tested but peaked at 0.10 mmol Cr(VI)/kg, whereas no increase in 8-oxo-dG levels over background levels was observed in liver of Cr(VI)-treated embryos. The possible role of glutathione in modulating Cr(VI)-induced DNA damage was examined by using L buthionine-R,S-sulfoximine (BSO) to deplete glutathione. No changes in glutathione levels were observed in either liver or red blood cells of embryos treated with Cr(VI) in the presence or absence of BSO pretreatment. Ascorbate levels in liver and red blood cells were not affected by treatment of embryos with chromium(VI), BSO or Cr(VI) and BSO. Depletion of glutathione by BSO resulted in a small increase of chromium uptake in liver of embryos treated with 0.050 and 0.10 mmol Cr(VI)/kg, but had no effect on hepatic chromium uptake at 0.20 mmol Cr(VI)/kg. BSO had no effect on chromium uptake in red blood cells. Depletion of glutathione had no effect on hepatic or red blood cells Cr-DNA binding in embryos treated with Cr(VI). However, depletion of glutathione significantly decreased the 8-oxo-dG levels in red blood cells at all Cr(VI) doses tested. Levels of 8-oxo-dG in liver of Cr(VI)-treated embryos remained at background in the presence or absence of BSO pretreatment. These results indicate that Cr(VI)-induced DNA damage in 14 day chick embryos is through a direct interaction of chromium with DNA in liver, but is through an indirect oxidative pathway in red blood cells. It appears that glutathione plays an important role in chromium(VI)-induced formation of 8-oxo-dG in red blood cells. PMID- 8001256 TI - Suppression of mitogenic activity by stable expression of the regulatory domain of PKC beta. AB - The amino-terminal regulatory domain portion of each protein kinase C (PKC) family member (which in the case of PKC beta 1 includes the pseudosubstrate, C1, V1 and C2 domains) plays an important role in regulating the kinase activity of the carboxyl-terminal catalytic domain. To examine the possibility that this regulatory domain region (designated 'PAT') might have biological functions independent of the catalytic domain, we have developed derivatives of R6 cells which stably express a truncated PKC beta 1 cDNA that encodes the amino-terminal 317 amino acids, including the entire regulatory domain. These R6-plPAT cells express abundant amounts of a 38 kDa protein which binds a labeled phorbol ester, but lacks protein kinase activity. In contrast to the 79 kDa PKC beta 1 holoenzyme which, when overexpressed in R6 cells, is found mostly in the cytosol, the 38 kDa PAT protein is predominantly associated with the particulate subcellular fraction. Furthermore, the PAT protein fails to show down-regulation following treatment of R6-plPAT cells with 12-O-tetradecanoylphorbol-13-acetate (TPA). Evidence is also presented that TPA-stimulated growth is suppressed in R6 plPAT cells. These findings suggest that the PKC beta 1 regulatory domain could be involved in the suppression of mitogenic signaling. PMID- 8001257 TI - Induction and mechanism of DNA single- and double-strand breaks by tetracycline/Cu(II) in the absence of light. AB - In the absence of light, tetracycline (TC) induced single- and double-strand breaks in PM2 DNA at micromolar concentrations in combination with CuCl2, whereas TC or CuCl2 alone had no effect. Strand break formation was completely suppressed by catalase and the specific Cu(I) scavenger neocuproine. The extent of strand break formation depended on the ratio of Cu(II):TC. At a ratio of > or = 2 most DNA damage was observed. The influence of the kind of Cu(II)/TC complexation on DNA strand break formation is discussed. The DNA damage in PM2 DNA provoked by TC/CuCl2 was indirectly detected also in human fibroblasts by the induction of DNA repair. The results are discussed with regard to human risk from TC/Cu(II). PMID- 8001258 TI - Bay- and fjord-region distortions in dibenz[a,j]anthracene and tetrabenzo[de,hi,mn,qr]naphthacene. AB - The crystal structure of 7,14-dimethyldibenz[a,j]anthracene (DMDBA) has been determined, and the crystal structure of tetrabenzo[de,hi,mn,qr]naphthacene (TBNC) has been redetermined at higher precision than previously reported. These molecules are polycyclic aromatic hydrocarbons (PAHs) that have, respectively, two hindered bay regions and two fjord regions; the former PAH is a known carcinogen. The extensive out-of-plane bending as a result of steric overcrowding in the bay and fjord regions in these PAHs is shown by these studies. For DMDBA, the angle between the 14-methyl group and the outer rings is 32.6 degrees. For TBNC, the angle between the outer rings of the molecule is 31.9 degrees. These structures are compared with those of related structures of 7,12 dimethylbenz[a]anthracene and dibenzo[g,p]chrysene. It appears that steric overcrowding in such PAHs can cause distortions of up to 33 degrees C. Such steric overcrowding will affect the conformations of bay- and fjord-region diolepoxides, which are the presumed activated metabolites in the carcinogenic process. PMID- 8001260 TI - Bile acids do not form adducts when incubated with DNA in vitro. AB - Bile acids have been implicated in the aetiology of colon cancer. We have previously found, using 32P-postlabelling, that bile from control patients and from patients with familial adenomatous polyposis (FAP) produces DNA adducts when incubated with salmon sperm DNA in vitro. In the present study we have incubated the common primary and secondary, conjugated and unconjugated bile acids with salmon sperm DNA in vitro, in both the presence and absence of metabolic activation (Aroclor-induced rat liver S9). The DNA was then purified and assayed for the formation of DNA adducts using the nuclease P1 method of 32P postlabelling. Under the conditions of the assay none of the bile acids tested with or without metabolic activation produced any evidence of DNA adduct formation. It is therefore unlikely that the adduct-forming ability of human bile can be attributed to bile acids or their metabolites. PMID- 8001259 TI - Phospholipid peroxidation in tumor promoter-exposed mouse skin. AB - We have investigated lipid peroxidation in the skin of CD1 mice following single or repeated topical applications of the tumor promoter, 12-O-tetradecanoylphorbol 13-acetate (TPA). A substantial accumulation of hydroxyphospholipids, to levels 3 5 times control values, followed exposure to two or more TPA treatments (24-72 h intervals), whereas single applications were ineffective. Sodium borohydride reduction increased the yield of product by approximately 50%, suggesting the additional presence of phospholipid hydroperoxides in the oxidized lipids. Straight phase HPLC analysis of the constituent hydroxy fatty acids, followed by gas chromatography/mass spectrometry, revealed that oxidized derivatives of linoleic acid, including 9- and 13-hydroxyoctadecadienoic acids (9- and 13-HODE), were the primary products. Stereochemical analysis showed ratios of S to R stereoisomers of 1.3 for 13-HODE and 1.27 for 9-HODE, which implied that TPA induced peroxidation was primarily due to free radical oxidation, although a partial contribution of enzyme (lipoxygenase) activity is possible. The TPA induced peroxidation was greater in the epidermis than in the dermis. Pre exposure of mouse skin to the anti-inflammatory agent fluocinolone acetonide, antioxidants and enzyme (phospholipase A2 and lipoxygenase) inhibitors lowered the peroxidation response to subsequent exposure to TPA. Phospholipid peroxidation products may be useful markers of oxygen radical production in TPA exposed mouse skin with possible relevance to tumor promotion. PMID- 8001261 TI - p53 mutations in larynx cancer. AB - The objective of this work was an analysis of mutations in the p53 gene detected from fresh tumor samples of larynx cancer patients using single-strand conformation polymorphism (SSCP) and direct DNA sequencing of exons 5-8. From 40 patient samples, 15 showed an extra band in SSCP. In 13 samples mutations were detected in exons 5-8. They constituted six transitions and seven transversions, four of them being T to A transversions. Mutations in codons 205 and 248 occurred in two and in codon 246 in three samples. Larynx cancer is strongly associated with tobacco smoking and alcohol consumption. The typical p53 mutations in lung cancer, G to T transversions and G to A and C to T transitions, associated with smoking, accounted for 46% of the mutations detected. Fifty-four per cent of the mutations were detected in a reported hotspot region covering codons 238-248. PMID- 8001262 TI - The sensitivity to camptothecin of DNA topoisomerase I in L5178Y-S lymphoma cells. AB - Sensitivity to camptothecin (CPT) of type I DNA topoisomerases isolated from two L5178Y (LY) sublines was examined in reaction media containing either aspartate or chloride. The enzyme from LY-S cells was sensitive to the drug in the presence of 120 mM K-aspartate, but the sensitivity was markedly reduced in the presence of 120 mM KCl. The enzyme from LY-R cells was similarly sensitive to camptothecin in the presence of either aspartate or chloride. The optimum ionic strength for the relaxation reaction catalyzed by both LY-R and LY-S type I DNA topoisomerases was similar. We suggest that sensitivity of the LY-S enzyme to CPT depends on the amount of cleavable complex formed, which in turn depends on the ionic conditions of the assay. PMID- 8001263 TI - Evidence for the simultaneous expression of alternatively spliced alkylpurine N glycosylase transcripts in human tissues and cells. AB - We have isolated a novel human alkylpurine N-glycosylase (APNG) cDNA from a placental library by screening with an oligonucleotide based on the published sequence of the human liver cDNA encoding this protein. The nucleotide sequences of the two cDNAs were essentially identical, but the 5' untranslated region of the new sequence was truncated and the 5'-terminal 92 nucleotides of the novel cDNA were different, indicating the possibility of alternative transcripts. This region included a portion of the open reading frame, so that the predicted protein was truncated and the seven N-terminal amino acids differed from the published sequence for APNG. PCR amplification of reverse transcribed mRNA, using 5' primers unique to the two cDNAs and a common 3' primer showed that the alternative transcripts can be co-expressed in the same cells and tissues. PMID- 8001264 TI - Functional significance of different human CYP1A1 genotypes. AB - At least two different polymorphisms in the human CYP1A1 gene have been associated with an increased risk for tobacco-related lung cancer; however, the functional significance of these polymorphisms has not been determined. We measured CYP1A1 genotypes, gene expression levels and enzymatic activity levels in mitogen-stimulated lymphocytes to determine whether genetic polymorphisms in CYP1A1 alter transcriptional and/or post-transcriptional regulation of the gene. Genotypes were determined at two sites previously associated with lung cancer: a point mutation in exon 7 near the catalytic region of the enzyme and an Msp1 RFLP in the 3' non-coding region of the gene. Variant genotypes at the Msp1 site had no effect on CYP1A1 gene induction, however, variant genotypes at the exon 7 site were significantly associated with increased CYP1A1 gene inducibility. We also observed a significant interaction between the exon 7 polymorphism and smoking on mRNA levels. There was a 3-fold elevation in CYP1A1 enzymatic activity in exon 7 variant genotypes. When Msp1 and exon 7 genotypes were combined, there was an increased CYP1A1 inducibility and enzymatic activity in subjects with the exon 7 polymorphism, and in subjects with both polymorphisms. PMID- 8001265 TI - DNA methylation adduct formation and H-ras gene mutations in progression of N butyl-N-(4-hydroxybutyl)nitrosamine-induced bladder tumors caused by a single exposure to N-methyl-N-nitrosourea. AB - After receiving 500 p.p.m. N-butyl-N-(4-hydroxybutyl) nitrosamine (BBN) in their drinking water for an initial 10 weeks, rats were given a single i.p. injection of N-methyl-N-nitrosourea (MNU) at a dose of 50 mg/kg body wt at week 20 (at a stage when bladder tumor development had already occurred), and then maintained until they were killed at week 40. Three and six hours after the MNU injection, the DNA methylation adducts, O6-methyldeoxyguanine (O6-medG) and 7 methyldeoxyguanine (7-medG), were immunohistochemically revealed to be markedly more frequent in urothelial preneoplasias or neoplasias than in normal cells. These adducts were rapidly repaired, and although 7-dmeG in tumor cells still persisted after 72 h, they appeared essentially to have returned to normal levels. At the termination, conversion of transitional cell carcinomas (TCC) to squamous cell carcinomas (SCC) of the urinary bladder was significantly increased in the BBN+MNU group. The extent of invasion was also significantly greater with the additional MNU treatment. Expression of p21 protein, detected by immunohistochemistry, was comparable between the groups. Mutations in the H-ras gene were observed in one case each of the BBN and BBN+MNU groups, and both cases showed a G:C to A:T transition at codon 12. The present study thus suggested that while an additional single treatment with MNU of rats bearing BBN-induced bladder neoplasias is associated with significant, possibly mutation-dependent tumor progression, H-ras mutations are not necessary events. PMID- 8001266 TI - Angiotensin II and other hypertrophic stimuli mediated by G protein-coupled receptors activate tyrosine kinase, mitogen-activated protein kinase, and 90-kD S6 kinase in cardiac myocytes. The critical role of Ca(2+)-dependent signaling. AB - Many hypertrophic stimuli such as angiotensin II (Ang II) activate phospholipases through G protein-coupled receptors in cardiac myocytes. However, it is not known whether these stimuli also activate the tyrosine phosphorylation-dependent signaling pathway, which plays an essential role in growth factor-induced mitogenic responses in other cell types. Serine/threonine kinases such as mitogen activated protein (MAP) kinases and 90-kD S6 kinase (RSK) are activated in response to many growth stimuli and are important downstream signaling pathways of tyrosine kinases. Therefore, we examined whether Ang II activates these protein kinases in primary cultures of cardiac myocytes and fibroblasts from neonatal rats. Ang II rapidly induced tyrosine phosphorylation of multiple proteins, including 42-, 44-, 75- to 80-, and 120- to 130-kD proteins, in both cardiac myocytes and fibroblasts. This was accompanied by an increase in tyrosine kinase activity. The 42- and 44-kD proteins were immunologically related to an extracellular signal-regulated kinase family (MAP kinases). Ang II rapidly increased kinase activity of MAP kinases and their downstream kinase, RSK. The Ang II-induced tyrosine phosphorylation and activation of MAP kinases and RSK were AT1 receptor-mediated. Activation of protein kinase C (PKC) by phorbol 12 myristate 13-acetate or an increase in intracellular Ca2+ by the Ca2+ ionophore A23187 was sufficient to cause tyrosine phosphorylation of multiple proteins and activation of MAP kinase and RSK. Although downregulation of PKC did not suppress Ang II-induced activation of MAP kinase and RSK, chelating intracellular Ca2+ by BAPTA-AM completely abolished Ang II-induced activation of these kinases. Activation of MAP kinases and RSK was also observed in myocytes stimulated with other agonists for Gq protein-coupled receptors, such as phenylephrine, norepinephrine, and endothelin 1, but not with agonists to Gs protein-coupled receptors, such as isoproterenol. These results suggest that Ang II and other hypertrophic stimuli, known to act through Gq protein-coupled receptors, rapidly cause tyrosine phosphorylation of several intracellular substrates through activation of tyrosine kinase and activate MAP kinases and RSK in cardiac myocytes as well as in cardiac fibroblasts. Furthermore, intracellular Ca2+, rather than PKC, seems to be critical for Ang II-induced activation of these protein kinases in cardiac myocytes. PMID- 8001267 TI - Inhibition and rapid recovery of Ca2+ current during Ca2+ release from sarcoplasmic reticulum in guinea pig ventricular myocytes. AB - We have investigated the modulation of the L-type Ca2+ channel by Ca2+ released from the sarcoplasmic reticulum (SR) in single guinea pig ventricular myocytes under whole-cell voltage clamp. [Ca2+]i was monitored by fura 2. By use of impermeant monovalent cations in intracellular and extracellular solutions, the current through Na+ channels, K+ channels, nonspecific cation channels, and the Na+-Ca2+ exchanger was effectively blocked. By altering the amount of Ca2+ loading of the SR, the time course of the Ca2+ current (ICa) could be studied during various amplitudes of Ca2+ release. In the presence of a large Ca2+ release, fast inhibition of ICa occurred, whereas on relaxation of [Ca2+]i, fast recovery was observed. The time course of this transient inhibition of ICa reflected the time course of [Ca2+]i. However, the inhibition seen in the first 50 ms, ie, the time of net Ca2+ release from the SR, exceeded the inhibition observed later during the pulse, suggesting the existence of a higher [Ca2+] near the channel during this time. Transient inhibition of ICa during Ca2+ release was observed to a similar degree at all potentials. It could still be observed in the presence of intracellular ATP-gamma-S and of cAMP. Therefore, we conclude that the modulation of ICa by Ca2+ release from the SR is not related to dephosphorylation. It could be related to a reduction in the driving force and to a direct inhibition of the channel by [Ca2+]i. The observation that the degree of inhibition does not depend on membrane potential suggests that the Ca2+ binding site for this modulation is located outside the pore.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8001268 TI - Cardiac electrophysiological actions of the histamine H1-receptor antagonists astemizole and terfenadine compared with chlorpheniramine and pyrilamine. AB - We compared the cardiac electrophysiological actions of two types of H1-receptor antagonists--the piperidines, astemizole and terfenadine, and the nonpiperidines, chlorpheniramine and pyrilamine-in vitro in guinea pig ventricular myocytes and in vivo in chloralose-anesthetized dogs. Astemizole and terfenadine significantly increased action potential duration of guinea pig myocytes. This concentration dependent prolongation of action potential duration was reverse frequency dependent and led to development of early afterdepolarizations, which occurred more frequently at higher concentrations and slower pacing frequencies. Astemizole and terfenadine potently blocked the rapidly activating component of the delayed rectifier, IKr, with IC50 values of 1.5 and 50 nmol/L, respectively. At 10 mumol/L, terfenadine but not astemizole blocked the slowly activating component of the delayed rectifier, IKs (58.4 +/- 3.1%), and the inward rectifier, IK1 (20.5 +/- 3.4%). Chlorpheniramine and pyrilamine blocked IKr relatively weakly (IC50 = 1.6 and 1.1 mumol/L, respectively) and IKs and IK1 less than 20% at 10 mumol/L. Astemizole and terfenadine (1.0 to 3.0 mg/kg IV) significantly prolonged the QTc interval and ventricular effective refractory period in vivo. Chlorpheniramine and pyrilamine (< or = 3.0 mg/kg) did not significantly affect these parameters. Block of repolarizing K+ currents, particularly IK1, by astemizole and terfenadine produces reverse rate-dependent prolongation of action potential duration and development of early afterdepolarizations, delays ventricular repolarization, and may underlie the development of torsade de pointes ventricular arrhythmias observed with the use and abuse of these agents. PMID- 8001269 TI - Patterns of capillary plasma perfusion in brains in conscious rats during normocapnia and hypercapnia. AB - The present study aimed to investigate the distribution pattern of plasma flow velocities in brain capillaries. We tested the hypothesis that plasma flow velocities are heterogeneous in the brain capillaries of normocapnic conscious rats and become more homogeneous during increased cerebral blood flow induced by hypercapnia. We developed a method that makes it possible to detect the distribution pattern of plasma flow velocities from the intravascular dye concentrations measured in different capillaries. Evans blue was injected intravenously as a bolus, and 3 to 4 seconds later the rats were decapitated. During this period, a steep increase in arterial dye concentration was verified by frequent arterial blood sampling. Under such conditions, divergent plasma flow velocities in different capillaries yield unequal intravascular dye concentrations. Dye concentrations were measured in several hundred capillaries of brain cryosections using quantitative fluorescence microscopy based on calibration curves obtained from anesthetized rats. The results show a high degree of variation in the intravascular dye concentration during normocapnia. During increasing stages of hypercapnia, the variation was gradually reduced. The coefficient of variation (SD/mean-100) of intracapillary dye concentration decreased from 76% at normocapnia to 22% at extreme hypercapnia (PCO2 of 87 mm Hg), thus showing an inverse correlation with arterial PCO2 (r = .97). The heterogeneity of intravascular dye concentrations observed in the present experiments indicates heterogeneous velocities of plasma perfusion in different brain capillaries during normocapnia and a more homogeneous distribution pattern during hypercapnic hyperemia. PMID- 8001271 TI - systolic flow augmentation in hearts ejecting into a model of stiff aging vasculature. Influence on myocardial perfusion-demand balance. AB - Age-related arterial stiffening and widening of the pulse pressure elevates ventricular systolic wall stress while it lowers diastolic coronary perfusion pressure. These changes are thought to adversely alter the balance between myocardial work load and blood supply. To test this hypothesis, the native compliant thoracic aorta was surgically bypassed by a stiff tube in reflex blocked anesthetized dogs. Ventricular outflow was directed into either native aorta or the bypass; the latter resulting in an increase in arterial pulse pressure from 37.8 to 107.5 mm Hg (P < .001), with minimal change in mean pressure and flow. Cardiac work load was assessed by pressure-volume area (PVA), which combines external and internal left ventricular work and is linearly related to myocardial oxygen consumption (MVO2), and by MVO2 itself. Regional phasic and mean coronary flow were measured in the left anterior descending coronary artery, and global flow was assessed by radiolabeled microspheres. Myocardial supply-demand balance was assessed by comparing flow at matched PVA or MVO2, flow-PVA relations, and endocardial-to-epicardial flow ratios. When blood flow was directed into the stiff bypass tube, peak systolic pressure, wall stress, and PVA all rose nearly 50%, yet diastolic perfusion pressure fell by 20 mm Hg (all P < .01). Rather than being compromised, however, mean coronary flow rose by 34%, maintaining the same endocardial-to-epicardial flow ratio (approximately 1.1). Flow augmentation persisted when data were compared at matched work load (PVA or MVO2), and mean arterial pressure, as well as over a range of work loads (P < .001 from ANCOVA of flow-PVA relations). The increased flow resulted from enhanced systolic perfusion, which nearly equaled diastolic flow when ejection passed into the stiff bypass. These data counter the notion that cardiac coupling with a stiff arterial system (as with aging) necessarily compromises myocardial flow versus metabolic demand. However, the data highlight a greater role of systolic flow under such conditions and also raise the novel suggestion that enhanced pulsatility of the arterial pressure waveform may itself augment coronary perfusion. PMID- 8001272 TI - Alterations in the expression of the genes encoding specific muscarinic receptor subtypes in the hypothalamus of spontaneously hypertensive rats. AB - A significant body of evidence exists that is consistent with the possibility that heightened cholinergic activity in certain brain regions, such as the hypothalamus, leads to increased sympathetic tone and subsequent hypertension. The increase in cholinergic activity is mediated at least in part through enhanced sensitivity of muscarinic receptors. In this study, we used the technique of reverse transcriptase-polymerase chain reaction to estimate the relative levels of mRNA encoding the five known subtypes of muscarinic receptors within the hypothalamus of spontaneously hypertensive rats (SHR), a genetic model of the disease, and their normotensive counterparts (Wistar-Kyoto rats). SHR exhibited a significant increase (40% to 50%) in the excitatory M1 subtype (confirmed by receptor binding) and a decrease in the inhibitory M4 subtype of muscarinic receptors before and during the establishment of hypertension. Such alterations may form part of the genotypic profile of inherited hypertension. PMID- 8001273 TI - Salt-sensitive hypertension in transgenic mice overexpressing Na(+)-proton exchanger. AB - Essential hypertension is one of the most common diseases that exacerbate the risk of cardiovascular or cerebrovascular attacks. Although the etiology of essential hypertension remains unclear, recent investigations have revealed that an enhancement of Na(+)-proton (Na(+)-H+) exchange activity is a frequently observed ion transport abnormality in hypertensive patients and animal models. To test the hypothesis that increased Na(+)-H+ exchange causes hypertension, we produced transgenic mice overexpressing Na(+)-H+ exchanger and analyzed their Na+ metabolism and blood pressure. Urinary excretion of water and Na+ was significantly decreased in transgenic mice, and systolic blood pressure was elevated after salt loading. The impaired urinary excretion of Na+ suggested that the Na(+)-H+ exchanger overexpressed in the renal tubules increased reabsorption of Na+, which caused a blood pressure elevation by Na+ retention after excessive salt intake. Our results demonstrate that overexpression of Na(+)-H+ exchanger can be a genetic factor that interacts with excessive salt intake and causes salt sensitive blood pressure elevation. PMID- 8001270 TI - Central command increases muscle sympathetic nerve activity during intense intermittent isometric exercise in humans. AB - During sustained isometric exercise, central command has very little effect on muscle sympathetic nerve activity (MSNA). To determine if central command has a greater effect on MSNA during intermittent than during sustained contractions, MSNA was recorded with microelectrodes (peroneal nerve) during intermittent isometric handgrip at 25%, 50%, and 75% maximum voluntary contraction (MVC) in 9 human subjects with paced breathing. Similar experiments were performed in 11 additional subjects before and after partial neuromuscular blockade (intravenous curare) to isolate the influence of central command while minimizing force output and thus muscle afferent feedback. Before curare, handgrip at 25% and 50% MVC had no effect on MSNA, whereas handgrip at 75% MVC synchronized the MSNA to the handgrip such that MSNA was 5.7 +/- 1.3 times higher (mean +/- SEM, P < .001) during the contraction periods than during the relaxation periods. After curare, this synchronization of MSNA persisted without attenuation, even though force output fell to < 25% of the initial MVC. From these observations, we conclude that central command causes synchronization of motor activity and muscle sympathetic activity during intense intermittent isometric exercise. PMID- 8001274 TI - Rate of tension development in cardiac muscle varies with level of activator calcium. AB - In skeletal muscle, the rate of transition from weakly bound to force-generating crossbridge states increases as calcium concentration is increased. To examine possible calcium sensitivity of this transition in cardiac muscle, we determined the kinetics of isometric tension development during steady activation in detergent-permeabilized rat ventricular trabeculae (n = 7) over a range of calcium concentrations. Force-generating crossbridges in activated trabeculae were disrupted by a brief, rapid release and restretch equivalent to 20% muscle length (15 degrees C), which resulted in a subsequent phase of tension redevelopment that was well fit by a monoexponential function (rate constant, ktr). Sarcomere length was monitored by laser diffraction and held constant during tension redevelopment by an iterative adaptive feedback control system. The ktr increased from 3.6 +/- 0.8 s-1 at the lowest calcium concentration studied (pCa 5.9) to 9.5 +/- 1.3 s-1 during maximal activation (pCa 4.5). The relationship between relative ktr and relative tension was approximately linear over a wide range of [Ca2+] (r2 = .94). This result differs quantitatively from results in skeletal muscle, in which ktr is sensitive to [Ca2+] primarily at higher activation levels. This observation is also inconsistent with a recent suggestion that the rate of force development in living myocardium is independent of the activation level. Our results in skinned myocardium can be explained by a model in which calcium is a graded regulator of both the extent and rate of binding of force-generating crossbridges to the thin filament. PMID- 8001275 TI - K+ channel blockers inhibit tissue factor expression by human monocytic cells. AB - Human monocytes express the important procoagulant protein, tissue factor (TF), after stimulation by a variety of agents, including bacterial lipopolysaccharide (LPS). Monocyte TF expression may contribute to intravascular coagulation in a number of disease states. The present studies show that monocytic cell TF expression can be inhibited by several agents known to block cellular K+ channels. Exposure of human peripheral blood to 100 ng/mL LPS for 2 hours led to pronounced TF procoagulant activity associated with the mononuclear cell fraction. This was inhibited by 4-aminopyridine (2 mmol/L), tetraethylammonium chloride (10 mmol/L), and apamin (1 mumol/L). In contrast, charybdotoxin (100 nmol/L) was inactive. More detailed studies were carried out in cultured human monocytic tumor THP-1 cells. These cells exhibited low but detectable levels of TF mRNA, measured by reverse transcription and polymerase chain reaction; cell surface procoagulant activity, measured by a plasma clotting assay; and cell homogenate TF antigen, measured by immunoassay. Exposure of THP-1 cells to 1 microgram/mL LPS led to threefold to fivefold increases in all three parameters. Basal and LPS-induced levels of all three parameters were reduced in a dose dependent manner by 4-aminopyridine (I50, 1 mmol/L) and tetraethylammonium chloride (I50, 20 mmol/L) but not by apamin or charybdotoxin. Expression of TF activity was also inhibited by glibenclamide, an inhibitor of ATP-dependent K+ channels (I50, 25 mumol/L). These results suggest that facilitation of TF synthesis may be an important role for K+ channels in monocytes. PMID- 8001276 TI - Differentiation of vascular smooth muscle cells and the regulation of protein kinase C-alpha. AB - Dedifferentiation and proliferation of vascular smooth muscle cells (VSMCs) are important features of atherosclerosis. The molecular mechanisms are largely unclear; however, protein kinase C (PKC) is a key enzyme in the intracellular signaling pathways that mediate this process. We studied the activity and immunoreactivity of PKC-alpha in primary cultures of VSMCs from rat aortas under different conditions of growth and differentiation. PKC-alpha was determined under the following conditions: (1) during the growth phase and after confluence of cultured (passages 1 through 3) VSMCs, (2) before and after induction of differentiation in VSMCs by retinoic acid, and (3) in primary cultures of VSMCs from spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY) rats during early passages. PKC activity was measured by in vitro substrate phosphorylation. PKC-alpha immunoreactivity was assessed by Western blot using specific polyclonal antibodies and by immunostaining with confocal microscopy. Cell proliferation was measured by direct count. The cell phenotype was characterized by immunostaining and Western blot for alpha-actin and desmin. PKC-alpha expression and PKC activity during VSMC growth showed a decrease during rapid growth and an increase in confluent cells. This pattern was associated with the respective changes in cell differentiation. Retinoic acid induced an increase in PKC-alpha expression together with a more differentiated phenotype. Subcultured, rapidly growing VSMCs from SHR showed a decreased PKC-alpha expression compared with cells from WKY rats. To establish cause and effect, we next microinjected either PKC-alpha or inactivated material directly into dedifferentiated cells. We found that cells injected with active PKC-alpha expressed increased amounts of actin compared with control cells.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8001277 TI - Beta 2-adrenergic receptor actions in neonatal and adult rat ventricular myocytes. AB - The physiological function of beta 2-adrenergic receptors in the neonatal and adult heart is incompletely understood, and possible age-dependent differences in beta 2-receptor actions have not been considered. We used isoproterenol (mixed beta 1- and beta 2-receptor agonist) and zinterol (beta 2-selective agonist) to compare beta-receptor subtype actions in neonatal and adult rat ventricular myocytes. When delivered as a bolus at a final concentration of 10(-7) mol/L, both isoproterenol and zinterol increased the amplitude and hastened the kinetics of the calcium and cell-shortening transients in neonatal myocytes. Under identical experimental conditions, isoproterenol increased the amplitude and accelerated the kinetics of the calcium transient and the twitch in adult myocytes, whereas zinterol did not. In the presence of CGP 20712A (beta 1 receptor blocker), a 100-fold higher concentration of zinterol increased the amplitude but prolonged the duration of the twitch in adult myocytes. To probe the mechanism for this age-dependent difference in beta 2-receptor responsiveness, we compared beta-receptor expression and stimulation of cAMP accumulation in neonatal and adult myocytes. beta-Receptor density was 44,339 +/- 5178 sites per cell in neonatal myocytes and 186,346 +/- 13,356 sites per cell in adult myocytes; the relative proportion of beta 2-receptors was comparable in each (16.7 +/- 2.3% and 16.9 +/- 0.9%, respectively). Isoproterenol induced a large increase in cAMP accumulation in neonatal and adult myocytes (20.0 +/- 1.0- and 20.6 +/- 2.6-fold over basal). In contrast, zinterol evoked a substantial increase in cAMP accumulation in neonatal myocytes but only a minor increase in adult myocytes. These studies provide evidence that at low agonist concentrations, beta 2-receptor activation contributes to the positive inotropic response by increasing cAMP and increasing the amplitude and hastening the kinetics of the twitch in neonatal, but not adult, myocytes. Moreover, these results suggest that age-dependent differences in beta 2-receptor coupling to more distal elements in the signaling cascade can influence myocyte beta 2 receptor responsiveness. PMID- 8001278 TI - ATP-sensitive K+ channels mediate alpha 2D-adrenergic receptor contraction of arteriolar smooth muscle and reversal of contraction by hypoxia. AB - Evidence in rat skeletal muscle suggests that local metabolic control of blood flow is facilitated by the reliance on alpha 2D-adrenergic receptors (ARs) for constriction of arterioles, together with the strong sensitivity of this constriction to inhibition by hypoxia. The present study examined the role of ATP sensitive K+ (KATP) channels in the selective interaction between alpha 2D-ARs and hypoxia. Arterioles from rat cremaster muscle that possess both alpha 1D (alpha 1A/D)- and alpha 2D-AR subtypes were microcannulated, pressurized, and isolated in a tissue bath for measurement of changes in lumen diameter. Three studies first examined whether stimulation of alpha 2D- and alpha 1D-ARs involves inhibition of the KATP channel. Concentration-dependent constriction by the KATP antagonists glibenclamide (GLB, 0.01 to 10 mumol/L) and disopyramide (0.001 to 1 mmol/L) were abolished during alpha 2D stimulation but unaffected during alpha 1D stimulation. Activation of the KATP channel by cromakalim inhibited alpha 2D constriction with greater potency than alpha 1D (EC50, 7.0 +/- 0.2 versus 6.3 +/- 0.1). Finally, GLB (0.5 mumol/L) abolished dose-dependent alpha 2D constriction, whereas alpha 1D was unaffected. These data suggest that alpha 2D but not alpha 1D stimulation is "coupled" with closure of the KATP channel, leading to depolarization and contraction of vascular smooth muscle. In a second series, hypoxic (PO2, 6 mm Hg) inhibition of intrinsic smooth muscle tone was completely reversed by 0.1 mumol/L GLB, concentration-dependent GLB constriction was enhanced during hypoxia, and hypoxia reversed GLB constriction. These data confirm reports by others that hypoxia potentiates the activation of KATP channels, leading to hyperpolarization and relaxation. Finally, GLB constriction, which was abolished by concomitant alpha 2D stimulation, was completely restored by simultaneous activation of KATP channels with hypoxia. These findings suggest that the sensitivity of alpha 2D-AR constriction to inhibition by hypoxia arises through "antagonistic coupling" between these two stimuli, by which the alpha 2D AR inhibits and hypoxia activates KATP channels. PMID- 8001279 TI - Antibody-mediated imbalance of myocardial energy metabolism. A causal factor of cardiac failure? AB - The ADP-ATP carrier of the inner mitochondrial membrane is an autoantigen in myocarditis and dilated cardiomyopathy. Sera of patients with these diseases contain carrier-specific autoantibodies that inhibit the transmembrane nucleotide transport on isolated mitochondria. Guinea pigs immunized with the isolated ADP ATP carrier protein also generate specific carrier-inactivating antibodies. In this study, we measured the cardiac function of guinea pigs immunized with the ADP-ATP carrier by determining the external heart work (EHW) of their isolated perfused spontaneously beating hearts stimulated by 4.0 mmol/L calcium and aortic ligature. Further, the electrogenic transport activity of the ADP-ATP carrier was estimated by calculating the cytosolic-mitochondrial difference of the phosphorylation potential of ATP [delta G(cyt-mit)] in the freeze-clamped isolated hearts by nonaqueous fractionation. The EHW of immunized guinea pigs was seen to be reduced by 54% (P < .005) compared with nonimmunized control guinea pigs, and delta G(cyt-mit) declined from 4.9 kJ/mol ATP in nonimmunized control hearts to 2.3 kJ/mol ATP in the hearts of the immunized guinea pigs (P < .005). The decisive result of this study, however, is the close relation observed between the magnitude of reduction of delta G(cyt-mit) and the size of the decrease in EHW (r = .87). Therefore, it seems plausible that antibody-mediated carrier dysfunction (creating the observed imbalance in myocardial energy metabolism) is responsible for the impairment of cardiac function. Our data support the hypothesis that immunopathic mechanisms in myocarditis and dilated cardiomyopathy can trigger subsequent heart failure.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8001281 TI - Effect of adenosine on myocardial 'stunning' in the dog. AB - Recent evidence suggests a cardioprotective effect of adenosine in myocardial ischemia and reperfusion. The present study was undertaken to determine (1) whether adenosine attenuates myocardial stunning, (2) if so, whether the beneficial effect of adenosine takes place during ischemia or after reperfusion, and (3) whether adenosine preconditions against myocardial stunning. A total of 93 dogs were used. In phase A of the study, open-chest dogs undergoing a 15 minute occlusion of the left anterior descending coronary artery followed by 4 hours of reperfusion received an intracoronary infusion of either saline (group I [control], n = 14), 2 mg/min adenosine from 30 minutes before occlusion until 1 hour after reperfusion (group II, n = 10), or 2 mg/min adenosine from 2 minutes before reperfusion until 1 hour after reperfusion (group III, n = 11). Regional myocardial function (assessed as systolic wall thickening) was similar in the three groups at baseline and during ischemia. After reperfusion, dogs treated with adenosine before, during, and after ischemia (group II) demonstrated a significant improvement in the recovery of function that persisted throughout the 4 hours of reperfusion. In contrast, in dogs treated only during the reperfusion period (group III), the recovery of function was not statistically different from that in control dogs. The enhanced recovery effected by adenosine in group II could not be ascribed to differences in ischemic zone size, collateral flow during occlusion, coronary flow after reperfusion, arterial pressure, heart rate, or other hemodynamic variables. In phase B of the study, dogs received an intracoronary infusion of either saline (group IV [control], n = 6) or adenosine (4 mg/min from 40 to 10 minutes before occlusion [group V, n = 6]). Despite pretreatment with adenosine, the recovery of function in group V was indistinguishable from that in the control group. This study demonstrates that (1) continuous administration of adenosine before, during, and after ischemia results in a significant and sustained attenuation of myocardial stunning; (2) this improved recovery of function cannot be attributed to nonspecific variables, such as collateral flow during coronary occlusion, coronary flow after reperfusion, or other hemodynamic factors, and therefore reflects a direct cardioprotective action of adenosine; (3) the protection against stunning is lost or markedly diminished if adenosine is given only at reperfusion; and (4) administration of adenosine before ischemia does not precondition the myocardium against the stunning induced by a 15-minute occlusion.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8001280 TI - Preconditioning of isolated rat heart is mediated by protein kinase C. AB - Catecholamines have been implicated in the phenomenon of ischemic preconditioning. We have previously demonstrated that ischemic preconditioning against postischemic mechanical dysfunction in the isolated rat heart is mediated by the alpha 1-adrenergic receptor. The purpose of this study was to delineate the signal transduction of preconditioning distal to the alpha 1-adrenergic receptor. Our results suggest that (1) transient ischemia and alpha 1-adrenergic receptor-induced preconditioning is inhibited by protein kinase C (PKC) antagonists, (2) functional protection against global ischemia/reperfusion injury can be induced by infusion of diacylglycerol, the second messenger of the alpha 1 adrenergic pathway, and (3) transient ischemia and alpha 1-adrenergic preconditioning are both characterized by similar translocation of PKC-delta to the sarcolemma of myocardium. These findings suggest that PKC is an effector of preconditioning in the isolated rat heart. PMID- 8001282 TI - Role of adenosine in postischemic dysfunction of coronary innervation. AB - We sought to determine the role of adenosine in the sustained but reversible decrease in cardiac neurotransmission that occurs after brief ischemia. Adult mongrel dogs were anesthetized and instrumented for measurements of heart rate, arterial pressure, and left anterior descending coronary artery (LAD) and left circumflex coronary artery (LCX) flow velocities. Changes in coronary vascular resistance were measured during bilateral stimulation of the stellate ganglia. After beta-adrenergic blockade and bilateral vagotomy, stellate stimulation increased coronary vascular resistance in the LAD and LCX beds 28 +/- 2% and 30 +/- 3%, respectively. After a 15-minute infusion of adenosine into the LAD, the peak increase in LAD resistance was significantly reduced (18 +/- 2%) compared with LCX (34 +/- 5%) and control (P < .05, n = 6) resistance. The LAD response after infusion of the vasodilator papaverine was unchanged (n = 6). Intracoronary infusion of adenosine deaminase (n = 10) but not vehicle (n = 5) into the LAD during a 15-minute LAD occlusion prevented the attenuation in constriction to stellate stimulation. We conclude that adenosine, exogenously infused or endogenously produced, is capable of reducing cardiac neurotransmission. PMID- 8001284 TI - Quercetin in our diet: from potent mutagen to probable anticarcinogen. PMID- 8001283 TI - Biochemical studies in head and neck cancer. PMID- 8001286 TI - Immunochemical detection of human lactoferrin in feces as a new marker for inflammatory gastrointestinal disorders and colon cancer. AB - We have developed a new immunochemical test for fecal lactoferrin (LF) utilizing an enzyme-linked immunosorbent assay (ELISA). The ELISA had a sensitivity of about 10 micrograms/L of lactoferrin and the measurable range was 10.0-1000.0 micrograms/L (1.0-100.0 micrograms LF/g feces). The stability of lactoferrin in feces was greater than that of myeloperoxidase and leucocyte elastase. The fecal concentration of lactoferrin (mean +/- SD) in 35 normal subjects was 0.75 +/- 0.83 microgram/g feces, whereas that in 24 patients with colon cancer was 74.4 +/ 88.3 micrograms/g feces. The fecal lactoferrin concentration of 38 patient with active ulcerative colitis was 307.4 +/- 233.9 micrograms/g feces, and that in 36 patients with active Crohn's disease was 191.7 +/- 231.1 micrograms/g feces. The ELISA for human fecal lactoferrin might be useful in the diagnosis of colon disease. PMID- 8001285 TI - Low-density lipoprotein binding assay using the calf adrenocortical low-density lipoprotein receptor. AB - The low-density lipoprotein (LDL) receptor was purified to a semipure solubilized form from calf adrenocortical tissue. This receptor was found to be a suitable substitute for the human LDL receptor for studying human LDL binding. The apparent dissociation constant of the receptor from calf adrenocortical cells, using human LDL as the ligand, was found to be 8.8 +/- 1.0 micrograms 125I LDL/mL, similar to that reported for the human LDL receptor (4-10 micrograms LDL/mL). The calf adrenocortical LDL receptor demonstrated specificity toward human lipoprotein fractions that was identical with that of the human LDL receptor. A competitive binding assay was optimized using the semipurified solubilized calf adrenocortical receptor. This facilitated the study of nonenzymatically glycosylated human LDL by a binding assay that is much simpler and faster than previous studies, which used intact cultured cells. The present assay requires only a 1-h incubation of LDL with the receptor and a simple filtration procedure to remove unbound LDL. Using the present assay, it was shown that nonenzymatic glycosylation of LDL on the order of what is seen in diabetics, that is, modification of 2-5% of lysine residues, caused a decreased ability of the LDL to bind to the receptor. PMID- 8001287 TI - Detection of familial defective apolipoprotein B-100 among patients clinically diagnosed with heterozygous familial hypercholesterolemia in maritime Canada. AB - Familial defective apolipoprotein B-100 (FDB) is a genetic disorder resulting from a mutation in the apolipoprotein B-100 (apo B-100) gene, most frequently at position 3500, in which arginine is substituted for glutamine in the mature protein. This mutation drastically decreases the affinity of the mutant apo B-100 particle for the low-density lipoprotein (LDL) receptor, and hence decreases the clearance of cholesterol from the circulation. Familial hypercholesterolemia (FH), also a disorder of lipid metabolism, results from mutations in the gene for the LDL receptor. Both FDB and heterozygous FH occur at approximately the same frequency (1 in 500) among Caucasians and both produce clinical symptoms and signs that can be indistinguishable. Polymerase chain reaction (PCR) amplification and subsequent restriction analysis have been used to detect the substitution at codon 3500 in the apo B-100 gene using mutagenic PCR primers. At least one proband from 10 unrelated families with a history of hypercholesterolemia was screened by mutagenic PCR for FDB. Only one of 10 patients demonstrated the mutation for FDB. The mutant apo B-100 allele was shown to segregate with other clinically affected family members. These results demonstrate that molecular analysis is essential to distinguish between FDB and heterozygous FH in hypercholesterolemic families. PMID- 8001288 TI - Uremic toxins and adenosine deaminase activity. AB - Predialysis erythrocyte adenosine deaminase activity was depressed in 12 of 20 patients receiving hemodialysis. In contrast, in 17 patients a marked rise in enzyme activity was observed subsequent to dialysis. Six patients had evidence of neuropathy. Predialysis plasma inhibited normal enzyme activity by an average of 36%, but postdialysis plasma had minimal inhibitory effect. A low molecular weight substance or substances, isolated from the dialysate of uremics, inhibited adenosine deaminase activity by 38%. Three patients having the longest courses of dialysis had no neuropathy and showed no depression of activity, with their plasma failing to inhibit normal activity. It is suggested that accumulation of low molecular weight toxins that depress adenosine deaminase activity may lead to myelin sheath degeneration with subsequent neuropathy. By removing the inhibitor, dialysis may permit nerve repair and eventual recovery. PMID- 8001290 TI - Effect of age and disease on two drug binding proteins: albumin and alpha-1- acid glycoprotein. AB - The influence of age and disease on serum albumin and alpha-1-acid glycoprotein was studied in 126 subjects (69 M, 57 F) presenting with tuberculosis and after recovery. Albumin concentration fell with age in both disease and healthy states, and alpha-1-acid glycoprotein concentration rose with age in the healthy state. Age-related differences were less marked in the disease state. During recovery from illness, serum albumin concentration rose and alpha-1-acid glycoprotein concentration fell. The mean concentration difference in the latter was lower in the older age groups. The clinical consequences of changes in binding protein concentrations as a result of ageing and disease need to be studied further for individual drugs. PMID- 8001289 TI - Monoclonal antibodies specific for 18-hydroxycortisol and their use in an enzyme immunoassay for human urinary 18-hydroxycortisol for diagnosis of primary aldosteronism. AB - We report the development of a monoclonal antibody-based enzyme immunoassay (EIA) specific for human urinary 18-hydroxycortisol, a biological marker of primary aldosteronism. Hybrid cell lines (hybridomas) were isolated after fusion between myeloma cells and spleen cells prepared from mice immunized with 18 hydroxycortisol conjugate. A competitive EIA suitable for the measurement of urinary 18-hydroxycortisol was developed using the mouse monoclonal antibody, KTM 41, which showed no practical cross-reaction with related endogenous steroids and synthetic steroids. This EIA meets all the requirements of routine clinical assay in terms of sensitivity (detection limit: 20 nmol/L), reproducibility (total CV: 8-15%), accuracy (recovery: 88-115%), simplicity and rapidity (< 3 h). Urinary 18 hydroxycortisol measured by the present assay was 153 +/- 119 nmol/L (mean +/- SD, range, 28-485) and 1787 +/- 1180 (range, 810-4264) in normal subjects (n = 20) and in patients with primary aldosteronism (n = 7), respectively. Clinical validation of the assay was confirmed by an appropriate decrease in urinary 18 hydroxycortisol level in patients with primary aldosteronism subsequent to adrenalectomy: 171 +/- 141 nmol/L (range, 41-466). PMID- 8001291 TI - ELISA for in vivo assessment of nonenzymatically glycated platelet glutathione peroxidase. AB - Using a combination of boronate affinity chromatography and ELISA methodology, a simple procedure was devised to selectively determine the in vivo glycated state of the platelet glutathione peroxidase (GSH-Px) from normal and diabetic subjects. The mean total GSH-Px levels in the normal (n = 14) and diabetic (n = 18) platelets were 1167 +/- 97 and 1007 +/- 73 ng/mg protein, respectively. The mean percentage glycated GSH-Px in the normal and diabetic platelets were 5.79 +/ 0.72% and 11.68 +/- 0.95%, respectively. When the percentage glycated GSH-Px was compared with the fructosamine values, a correlation coefficient of 0.71 was obtained. This indicates that the glycation status of platelet GSH-Px can be utilized as a sensitive, short-term index of plasma glucose levels. PMID- 8001292 TI - Glucose tolerance test during pregnancy: the significance of one abnormal value. AB - To determine the perinatal impacts of one abnormal oral glucose tolerance test (GTT) value, we conducted a retrospective study of pregnancy outcome in our population. Pregnant women (4314) were screened for gestational diabetes (GDM) between 24 and 32 weeks with the 50-g glucose challenge test and 183 were directly tested with the 100-g GTT. The subjects who had a serum glucose value equal or greater than 7.8 mmol/L 1 h after a 50-g glucose challenge were scheduled for a 100-g GTT (904). Another 32 subjects, who were not screened, were found to have gestational diabetes identified by repeated fasting and postprandial serum glucose measurements. Retrospectively, the study population was divided in four groups: I, normal (4138); II, GDM (237); III, subjects with one abnormal GTT value treated like GDM (85); IV, subjects with one abnormal GTT value untreated (69). Patient characteristics of groups II, III, and IV were similar. The area under the glycemic curve was similar between groups III and IV and was statistically inferior to that of Group II. GTT periodicity was the greatest in group II. Group II showed a higher rate of delivery before 37 weeks, of chronic and pregnancy induced hypertension, and of cesarian section but groups III and IV were not statistically different from group I.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8001293 TI - Lipoprotein levels in newborns and adolescents. AB - Previous studies established that cardiovascular disease can be predicted early in life. Active modification of risk factors in the general population should include screening as the first step. For this reason, lipoproteins and apolipoproteins were measured in newborns and adolescents. Almost all lipids and apolipoproteins were much lower at birth than at adolescence. Based on these results, reference ranges were calculated. PMID- 8001294 TI - Semiautomated determination of glycated albumin in glycaemic control of diabetic patients. PMID- 8001295 TI - Immunoturbidimetry of serum apolipoproteins A-I and B on the Cobas Bio centrifugal analyzer: method validation and reference values. AB - We describe an immunoturbidimetric assay for estimating the concentration of apolipoproteins (apo) A-I and B in serum with a Cobas Bio centrifugal analyzer. Several analytical variables were studied: pH, temperature, wavelength, reaction time, sample pretreatment, antisera dilution, concentration of NaCl, phosphate buffer, and PEG 6000; a good optical response was obtained with small volumes of sample and antisera. Imprecision was low, with intrarun coefficient of variance (CV) from 1.1 to 2.8% and interrun CV from 1.8 to 3.2%. We demonstrated a good correlation between our method and radial immunodiffusion for apo A-I (r = 0.975) and apo B (r = 0.980). Reference values were calculated from a sample of 494 healthy subjects, and separate intervals for the ratio of apo A-I to apo B in gender and age subgroups were established. PMID- 8001296 TI - Pediatric reference intervals for plasma renin. PMID- 8001297 TI - Asymptomatic cardiac ischemia: what is known and what remains unknown? PMID- 8001298 TI - Dyslipidemia and coronary artery disease. AB - Genetically determined and metabolically induced disturbances in lipid metabolism, as manifested in several types of dyslipidemia, have been shown to be causally related to the development of coronary artery disease (CAD). A diversity of clinical and angiographic studies has been made to evaluate the linkage between plasma lipid-control therapy in the development of initial and recurrent cardiovascular events. The plan of treatment invariably begins with a low-fat, low-cholesterol diet before initiation of drug therapy. However, many patients have difficulty in adhering to the low-fat diet. Fortunately, metabolic studies show that foods which contain fats rich in stearic (saturated) and oleic (monounsaturated) fatty acids may be given in limited amounts to boost patients' compliance to a low-fat diet and to prevent their blood lipids from rising to abnormal levels. A bile acid sequestrant (cholestyramine or colestipol) is the first-line drug for control of hypercholesterolemia. Either gemfibrozil or gemfibrozil plus niacin is prescribed to raise high-density lipoprotein (HDL) levels of CAD patients. Approval of two HMG CoA reductase inhibitors, pravastatin and simvastatin, by the FDA gives physicians the additional flexibility of employing a single or a combination drug therapy for optimal control of dyslipidemia. The association of low serum cholesterol level (< 160 mg/dl) with increase in noncardiac mortality has prompted health professionals to consider modifying the universal screening and treatment of serum cholesterol in children and young women and to use hypolipidemic drugs in patients judiciously. PMID- 8001299 TI - Clinical value of transesophageal atrial stimulation and recording in patients with arrhythmia-related symptoms or documented supraventricular tachycardia- correlation to clinical history and invasive studies. AB - The main objective of the present study was to evaluate the clinical applicability of transesophageal atrial stimulation (TAS) and recording with regard to inducibility of supraventricular tachycardia (SVT) in patients with either an ECG-documented paroxysmal SVT or a clinical history of palpitations suggesting this disease. A further objective was to assess the inducibility of SVT and to compare the inducibility by TAS with that obtained by an invasive electrophysiologic study (EPS). A total of 64 patients (aged 13-74 years) with ECG-documented paroxysmal SVT (n = 50) or only a history of palpitations (n = 14) was referred for TAS. Preexcitation was present in 35 patients. The study protocol included single and double extrastimuli delivered at a basic paced interval of 500 ms, and incremental atrial stimulation until a cycle length of 275 ms or a second-degree AV block appeared. In 10 patients atropine intravenously was required for induction. The same protocol was used in 34 of the patients who also underwent invasive EPS. TAS was completed in 56 of 64 patients (88%). In this group SVT was induced during TAS in 84% (47/56). Of patients with ECG-documented tachycardia, clinical tachycardia was induced in 90% (35/39) with ECG-documented regular paroxysmal SVT and in 67% of patients (4/6) with ECG documented atrial fibrillation. In patients without ECG-documented atrial fibrillation. In patients without ECG-documented tachycardia, clinically relevant arrhythmia was induced in 73% (8/11). In 30 of 32 patients (94%) with an inducible tachycardia during invasive EPS, it was also possible to induce the tachycardia by TAS.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8001300 TI - Long-term use of K-strophanthin in advanced congestive heart failure due to dilated cardiomyopathy: a double-blind crossover evaluation versus digoxin. AB - K-strophanthin or digoxin were added to diuretics (all cases) and vasodilators (most cases) for treating advanced congestive heart failure in 22 patients with dilated cardiomyopathy and sinus rhythm. K-strophanthin (0.125 mg intravenously) or digoxin (0.25 mg orally) were administered daily in two 3-month periods, during which vasodilators and diuretics were kept constant and patients received one of the two digitalis preparations in a double-blind fashion, crossing over to the alternative preparation in the next period. Blindness was assured throughout the trial with a daily intravenous injection of 10 ml normal saline solution either containing K-strophanthin or not, and with daily oral administration of either placebo or active digoxin. At the end of the run-in period, 15 days after starting active preparations, and thereafter every month for the next 6 months, we evaluated left ventricular pump function at rest and patients' functional performance by a cardiopulmonary exercise test. At Day 15, cardiac index and ejection fraction at rest, compared with run-in, were significantly raised with both glycosides; during exercise while on K-strophanthin, peak oxygen consumption was augmented by 1.4 ml/min/kg (p < 0.01) and oxygen consumption at anaerobic threshold by 2.2 ml/min/kg (p < 0.01); corresponding variations on digoxin (-0.1 and +0.3, respectively) were not significant versus run-in. These patterns were duplicated at repeated tests during follow-up.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8001301 TI - Postoperative hemodynamic improvement with paced linkage of the donor and recipient hearts following heterotopic cardiac transplantation. AB - It has been shown that following heterotopic heart transplantation the recipient left ventricle ejects more effectively when it contracts out of phase with the donor left ventricle. However, this is rarely the situation, as the two hearts beat independently of one another and the denervated donor heart tends to beat faster than the recipient. In this study the hemodynamic effects of connecting the two hearts by an external temporary dual-chamber pacemaker were evaluated. The donor right ventricle was sensed and the recipient right atrium paced after a timed delay. The delay was adjusted so that recipient systole coincided with donor diastole. Eleven patients were studied in the first postoperative day. Pacing resulted in an improvement in cardiac output from 5.0 to 5.6 l/min (p = 0.003) and a reduction in pulmonary capillary wedge pressure from 16 to 12 mmHg (p = 0.0035). This was associated with a 35% reduction in inotrope requirements. It is concluded that sequential pacing of the two hearts is a useful adjunct to inotropic support in the postoperative period. PMID- 8001302 TI - Spontaneous echo contrast on transthoracic echocardiography and left atrial thrombus in rheumatic mitral valve disease patients: a clinicopathologic study. AB - The association of spontaneous echo contrast and thrombus in the left atrium in patients with mitral valve disease is controversial. This study was undertaken to determine whether there is an independent association between spontaneous echo contrast on transthoracic echocardiography (TTE) and intraoperative evidence of left atrial thrombus and to evaluate the clinical implications of spontaneous echo contrast in patients with symptomatic rheumatic mitral valve disease. A total of 255 patients who underwent surgery for rheumatic mitral valve diseases were preoperatively evaluated by transthoracic two-dimensional and Doppler echocardiography. Spontaneous echo contrast in the left atrium was carefully sought. The left atrium was carefully searched for evidence of thrombus intraoperatively. The association of spontaneous echo contrast and left atrial thrombus was determined by univariate and multivariate analysis. Of the patients studied, 77 (30%) had left atrial thrombus. Left atrial thrombus was found in 47 and 21% of patients with and without spontaneous echo contrast, respectively (p < 0.001). Spontaneous echo contrast and atrial fibrillation were found to be the only two independent predictors of left atrial thrombus (odds ratio = 2.16; 95% confidence interval 1.15-4.04 p < 0.05, and odds ratio = 6.98; 95% confidence interval 3.45-14.16, p < 0.001, respectively). It was concluded that there is an independent association between spontaneous echo contrast on TTE and left atrial thrombus in patients with mitral valve disease requiring surgical correction. These patients are at high risk for left atrial thrombus and should, therefore, be considered for long-term anticoagulation. PMID- 8001303 TI - Emergency and long-term extracorporeal life support following acute myocardial infarction: rescue from severe cardiogenic shock related to stunned myocardium. AB - There has been no report regarding therapy of extracorporeal life support (ECLS) that showed stunned myocardium echocardiographically and electrocardiographically in patients with acute myocardial infarction. ECLS was performed in eight patients with cardiogenic shock or arrest unresponsive to catecholamines and intra-aortic balloon pumping following myocardial infarction; these patients required prolonged external cardiac massage. After the initiation of ECLS, both blood pressure and metabolic acidosis improved in all patients. Four of eight patients were weaned from ECLS after a mean of 69.3 h, which was far longer than previously reported in patients with ischemic heart disease. Three of these patients survived, and cardiac function recovered to NYHA class II in two of the survivors and class III in the other. The other five patients did not recover from coma during ECLS and died. A marked improvement of ventricular wall motion was seen in two survivors with the disappearance of pathologic Q waves after the initiation of ECLS. No occlusion of the coronary arteries or bypass grafts was observed in any of the survivors. These findings suggested the existence of stunned myocardium with myocardial reperfusion. The recovery of stunned myocardium may be delayed for days or even weeks, hence the extended period of ECLS therapy was theoretically justifiable. We conclude that long-term ECLS is a useful therapeutic method for patients with severe cardiogenic shock that is related to stunned myocardium. PMID- 8001304 TI - A multinational study of the effects of low-dose pravastatin in patients with non insulin-dependent diabetes mellitus and hypercholesterolemia. Pravastatin Multinational Study Group for Diabetes. AB - This multinational, 16-week, randomized, double-blind, placebo-controlled study evaluated the efficacy and safety of low-dose pravastatin in 325 patients with non-insulin-dependent diabetes mellitus (NIDDM) and hypercholesterolemia [serum total cholesterol concentrations of 5.2-7.8 mmol/l (200 to 300 mg/dl)]. Patients were randomized to receive pravastatin 10 mg or matching placebo with doubling of the dose after 8 weeks if predefined target levels for total cholesterol [(i.e., < 5.2 mmol/l (200 mg/dl) or > 15% decrease from baseline] had not been achieved. At Week 16, pravastatin-treated patients showed a 21.4% decrease in serum low density lipoprotein cholesterol (LDL-C) and a 13.5% reduction in serum total cholesterol (TC) concentrations (p < 0.001 compared with placebo). Levels of triglycerides (TG) were reduced 9.6% during pravastatin treatment (p < 0.05 compared with placebo) while high-density lipoprotein cholesterol (HDL-C) levels were increased 4.4% (p = NS). Adverse events and laboratory test abnormalities were similar among patients treated with pravastatin or placebo. Glycosylated hemoglobin (HbA1C) levels remained unchanged. The results of this study demonstrate that low-dose pravastatin is effective and well tolerated for lowering elevated cholesterol concentrations during short-term treatment of patients with NIDDM and hypercholesterolemia. PMID- 8001305 TI - Enterovirus-induced myocarditis: hemodynamic deterioration with immunosuppressive therapy and successful application of interferon-alpha. AB - In 1985, myocarditis was diagnosed by endomyocardial biopsy in a 53-year-old woman who was free of symptoms of heart insufficiency. Immunosuppressive therapy with azathioprine and prednisolone was prescribed as the patient had deteriorated to NYHA II heart insufficiency in March 1986. When application of immunosuppressive agents was terminated in 1987, serial endomyocardial biopsies revealed no signs of myocarditis, thus indicating effectiveness of immunosuppression. Nevertheless, the patient had worsened clinically and hemodynamically. At follow-up in 1991, the patient had progressed to dilated cardiomyopathy resulting in NYHA III heart insufficiency. Enterovirus infection of the heart was detected by in situ nucleic acid hybridization. In addition, retrospective serology indicated a significant increase of coxsackievirus B2 antibodies between 1985 and 1991. Investigational antiviral therapy with recombinant interferon alpha-2a was tolerated well and a favorable clinical, hemodynamic, and virologic response was observed. Thus, progression of biopsy proven myocarditis to dilated cardiomyopathy may have been facilitated by immunosuppressive therapy in enterovirus infection. Antiviral therapy might be advantageous in patients with enterovirus myocarditis and dilated cardiomyopathy. PMID- 8001306 TI - Post-traumatic pseudoaneurysm of the ascending aorta--an incidental finding two decades later. AB - Traumatic rupture of the aorta following blunt trauma is a well described entity. Rupture of the ascending aorta is frequently associated with concomitant cardiac damage and immediate death with few long-term survivors described in the literature. A case of traumatic pseudoaneurysm of the ascending aorta discovered two decades after the initial injury is reported. PMID- 8001307 TI - Pierre-Carl Potain. PMID- 8001308 TI - Noninvasive assessment of ventricular function at 90 minutes following thrombolytic therapy in patients with infarcting myocardium may predict coronary artery patency and prognosis. PMID- 8001309 TI - The toxic oil syndrome. AB - Hundreds died and thousands were poisoned by rapeseed oil adulterated with aniline and sold illegally in Spain in 1981. The clinical manifestations, now known as the toxic oil syndrome, include pulmonary hypertension and right ventricular hypertrophy plus widespread vascular and neural lesions in other organs. Many of the late deaths ended with a scleroderma-like illness. Because scleroderma involves the heart, an examination was made of the small and large coronary arteries, the neural structures, and the conduction system from 11 victims dying with the toxic oil syndrome. Dense fibrosis, atrionodal junctional hemorrhages, and cystic degeneration of the sinus nodes were present. Small and large coronary arteries exhibited focal fibromuscular dysplasia and a proliferative cystic myointimal degeneration. This latter abnormality was associated with sloughing of the inner wall and embolization of the detached fragment downstream in the same coronary artery. Every heart had many degenerative lesions within nerves, ganglia, and the coronary chemoreceptor. Based upon observations by others with experimental feeding of rapeseed oil containing either high or low erucic acid, it is suggested that this oil must remain a major suspected cause of the toxic oil syndrome, particularly in conjunction with some as yet unexplained facilitative influence by oleoanilids. If this is so, it is important to reexamine the widely recommended use of any rapeseed oil product as a suitable food for humans or animals. PMID- 8001310 TI - The clinical distinction between regional postinfarction pericarditis and other causes of postinfarction chest pain: ancillary observations regarding the effect of lytic therapy upon the frequency of postinfarction pericarditis, postinfarction angina, and reinfarction. AB - Recently two types of atypical T-wave evolution were recognized as electrocardiographic (ECG) markers of regional postinfarction pericarditis. The sensitivity and specificity of these changes for this condition were 100 and 77%, respectively. The major purpose of this investigation is to show how these ECG changes can be used to differentiate among postinfarction pericarditis, postinfarction angina, and reinfarction. Even appropriately constructed serial monitor lead ECGs can be used to make this distinction. The ease of correctly distinguishing among the three causes of postinfarction chest pain utilizing a carefully elicited history and ECG criteria is discussed. In addition, a secondary objective was to assess the effect of lytic therapy on the incidence of postinfarction pericarditis. Among the 200 patients in this study, lytic therapy halved the incidence of postinfarction pericarditis, which is in accord with the larger Gruppo Italiano per lo Studio della Streptochinasi nell'Infarto Miocardico (GISSI) study. PMID- 8001311 TI - The effect of successful angioplasty on variables of signal-averaged electrocardiogram and ventricular wall motion in patients with a first myocardial infarction. AB - The correlation among three variables of late potentials (LPs) obtained by signal averaged electrocardiography (SAECG) and improvement of ventricular wall motion estimated by echocardiography were studied in 66 patients with a first acute myocardial infarction (MI). Patients with bundle-branch block, intraventricular conduction delay, multi-vessel disease, previous MI, repeat percutaneous transluminal coronary angioplasty (PTCA), or evidence of reinfarction during a 6 month follow-up were excluded. A total of 66 patients was divided into two groups, with (Group 1: n = 27, age 56 +/- 11) or without (Group 2: n = 39, age 61 +/- 10) improvement of ventricular wall motion. Three variables of LPs and ventricular wall motion index (WMI) estimated and scored by echocardiography at admission (WMI 1) and at 6 months after MI (WMI 2) were compared in each group. In Group 1 (WMI 1 vs. WMI 2, p < 0.002), 20 of 27 patients underwent successful angioplasty; in Group 2 (WMI 1 vs. WMI 2, p = NS), 7 of 39 patients had successful emergency angioplasty. There were significant differences in three variables of LPs between the time of admission and at 6 months after MI in Group 1 but not in Group 2. Higher incidence of LPs and greater frequency of successful emergency PTCA were found in Group 1 compared with Group 2. These results suggest that because myocardial ischemia is reversed by successful angioplasty, ventricular wall motion is improved and the arrhythmogenic substrate that generates LPs is stabilized electrically. Stunned or hibernating myocardium may be the arrhythmogenic substrate that generates LPs. PMID- 8001312 TI - Conversion from immediate-release to extended-release diltiazem in angina pectoris. AB - This multicenter, open-label, single crossover study examined 195 patients taking an immediate-release diltiazem tablet as chronic stable angina therapy to determine if apparently logical methods of converting them to an extended release, once-daily formulation were effective. Patients were converted from the immediate-release (Phase I) to an extended-release (Phase II) formulation of diltiazem on a mg-for-mg basis or, when a similar dose was not available, to the next higher 120 mg dose. Weekly angina occurrences and nitroglycerin use, exercise testing at the end of each phase, and ambulatory electrocardiographic monitoring (AEM) during the week prior to the exercise study were evaluated. There was a statistically significant decrease in angina frequency and nitroglycerin consumption during Phase II. In the exercise studies, there was an insignificant increase in time to 1 mm ST-segment depression and total exercise time associated with a statistically significantly lower end-exercise blood pressure and heart rate in Phase II. In those patients who had ischemia during either phase on AEM, total ischemic duration and ischemic episodes were insignificantly lower in Phase II. All observations were similar in the subgroup of patients who were converted mg-for-mg. Adverse reactions were equal. Thus, in converting patients from an immediate- to an extended-release diltiazem formulation for the treatment of symptomatic coronary artery disease, it is reasonable to convert directly to the same or, if not available, the next higher available dose of the extended-release preparation. PMID- 8001314 TI - Reproducibility of the spectral turbulence analysis of the signal-averaged electrocardiogram. AB - Spectral turbulence analysis (STA) of the signal-averaged electrocardiogram (SAECG) is a recently proposed technique to identify patients with ventricular tachycardia as well as patients at risk for arrhythmic events after acute myocardial infarction (MI). The short-term reproducibility of this technique has been previously reported; our study evaluates the reproducibility of STA by shifting the reference points. Twenty patients with acute MI were recruited. SAECG was recorded 13 days after onset of the acute MI. Unfiltered data were transferred and analyzed by personal computer software for spectral turbulence analysis according to the standard condition; reference points of the segment of interest were shifted from QRS offset -10 ms and QRS onset -10 ms to QRS offset +10 ms and QRS onset +10 ms, step 2 ms. Thus, 10 analyses were computed. Reproducibility of the results was calculated using the coefficient of variation (CV) and the relative error (RE). The reproducibility of the classification (RC) was defined as the percentage of the identical classification compared with the standard segment. CV of the intersegment correlation standard deviation was statistically higher than the other parameters regardless of the lead considered. RE was not different in each parameter and in each lead. RC was > 90% in all parameters, except in spectral entropy which showed an RC > 80%. Reproducibility of the STA introducing a temporal shift in the analyzed segments was high in all considered parameters. PMID- 8001313 TI - Factors associated with the development of persistently depressed cardiac output during the first year after cardiac transplantation. AB - The purpose of this study was to determine factors associated with the development of a persistently depressed cardiac output during the first year after cardiac transplantation. With this aim in mind, the records of 133 consecutive patients undergoing orthotopic cardiac transplantation and surviving for > or = 1 year after transplantation were reviewed. For each patient, the mean cardiac index for each of the 3-month periods, 0-3, 4-6, 7-9, and 10-12 months after transplantation was calculated. Of the 133 patients, 19 (14%) had a mean cardiac index < 2.4 l/min/m2 during > or = 3 of these 3-month periods. The pre- and post-transplantation clinical, immunologic, and hemodynamic data of these 19 patients (study group) were compared with the remaining 114 patients (control group). Compared with the control group, the patients in the study group were older (56 +/- 5 vs. 46 +/- 15 years; p = 0.0001), more frequently had ischemic heart disease as the original diagnosis (58 vs. 37%; p < 0.05), had a lower preoperative cardiac index (1.91 +/- 0.53 vs. 2.71 +/- 1.0 l/min/m2; p = 0.0001), more frequently did not receive perioperative anti-T cell therapy (47 vs. 25%; p = 0.046), and had a greater median number of infections during the first year after transplantation (5 vs. 3; p = 0.027). However, only one factor--a low preoperative cardiac index--emerged as an independent predictor of the development of a persistently depressed cardiac index during the first year after transplantation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8001315 TI - Echocardiographic diagnosis of congenital absence of the pericardium in a patient with VATER association defects. AB - The VATER association denotes a nonrandom pattern of congenital malformations which typically include vertebral defects, anal atresia, tracheo-esophageal fistula, and radial and renal dysplasia. Vascular anomalies including ventricular septal defect and single umbilical artery have also been described, although the frequency of cardiovascular anomalies in this congenital association is unknown. In this report, we describe a 26-year-old patient with several VATER association defects who, in addition, was found to have congenital absence of the left pericardium and an aberrant right subclavian artery. PMID- 8001316 TI - Electrocardiographic and segmental wall motion abnormalities in pancreatitis mimicking myocardial infarction. AB - Transient electrocardiographic changes in patients with acute cholecystitis, pancreatitis, and pneumonia have been reported in the past. These changes usually are in the form of T-wave inversion, ST-segment depression, and rarely ST-segment elevation in the absence of coronary artery disease. To the authors' knowledge, this is the first report documenting both left ventricular segmental wall motion abnormality and electrocardiographic changes of myocardial injury in the presence of acute pancreatitis. PMID- 8001317 TI - Lewis E. January. PMID- 8001318 TI - History of in utero cocaine exposure in language-delayed children. AB - To determine whether children with language delays are more likely to have been exposed to cocaine in utero than children with normal language development, a case-control study was undertaken. Based on routine office screening in our primary-care clinic over a 1-year period, we identified 29 consecutive children, aged 24 to 48 months, as language-delayed. They were compared with an approximate 2:1 match of children without language delay who had been seen in the clinic on the same days and who were of similar age. There was more reported cocaine use during pregnancy (six of 29, 21%) among the language-delayed children than among the controls (five of 71, 7%). This difference is statistically significant (P < 0.05, chi 2 = 3.92; odds ratio = 3.4 +/- 2.2). Discriminant analysis revealed that both cocaine and nicotine exposure were associated with delayed language development--with an unexpected negative, i.e., an antagonistic, protective, interactive effect (F[3,96] = 4.66, R2 = 12.7%, P < .005); neither gender nor caretaker contributed to language development in this sample. These results suggest that children with language delay detected in a clinical setting are more likely to have been exposed in utero to cocaine than children with normal language development. Prenatal cocaine exposure should be a risk factor in monitoring development in children. PMID- 8001319 TI - Neuropsychological impairment in children with sickle cell anemia and cerebrovascular accidents. AB - Neuropsychological functioning of children with sickle cell anemia (HbSS) who have experienced a single stroke has not been extensively investigated. In this study, the neuropsychological functioning of 10 children with HbSS who were receiving transfusion therapy following stroke with no identifiable recurrence was examined. The patients were subgrouped into children with only left hemisphere stroke (LCI), N = 4, and those with only right hemisphere stroke (RCI), N = 6. Results indicated that these youngsters experienced significant impairments of cognitive functioning following stroke. It was found that the LCI and RCI children tended to perform more like adult stroke patients than what has been typically reported in children with infantile hemiplegia. These findings support the need for periodic neuropsychological evaluation following stroke in order to identify patterns of higher cortical dysfunction and assist in the development of appropriate rehabilitation and special education programs. Further, pediatricians, child neurologists, and psychologists who care for these children must act as strong advocates on their behalf in order to ensure that they receive appropriate rehabilitation and the special education services necessary for maximal recovery and future educational success. PMID- 8001320 TI - Prenatal counseling in heterozygotes for ornithine transcarbamylase deficiency. AB - X-linked ornithine transcarbamylase deficiency (OTCD) often leads to fatal neonatal hyperammonemia in affected males (hemizygotes). In prenatal management of subsequent pregnancies, families carrying female fetuses are often reassured of the low risk of clinically overt disease. We suggest that such reassurance may be misleading. While OTCD heterozygotes may show no symptoms or only mild protein intolerance, the clinical course in a fraction of children can include manifestations similar to those in affected males. We present three cases of symptomatic and previously undiagnosed OTCD heterozygotes to illustrate the potential severity of this condition. Significant improvement in function and growth followed diagnosis and treatment; however, two of the three children remain significantly developmentally delayed. While a quantitative risk estimate cannot be derived from these data, the cases are indicative of an adverse outcome in manifesting heterozygotes. Accordingly, OTCD carrier families should be counseled regarding the possibility of significant hyperammonemia, neurologic deficit, and the need for pharmacologic and dietary intervention in their heterozygote daughters. PMID- 8001321 TI - Diagnostic evaluation of short children with height 3 SD or more below the mean. AB - Most children who are more than 2 SD below the mean in height (less than third percentile) have no definable cause and are considered short-normal, but for children who are 3 SD below the mean (the lowest 0.13%), the prevalence of organic disease is known to be considerably greater. To better define the frequency of different diagnoses in this subgroup and to identify useful clinical findings, we reviewed the charts of all children referred for growth evaluation over a 10-year period who were > or = -3 SD in height, > 2 years old, and prepubertal. Of 60 patients (36 males and 24 females), 22% had constitutional growth delay (CGD), 23% had growth hormone deficiency (GHD), 13% had Turner syndrome, and 22% had various forms of primary growth failure (mostly associated with intrauterine growth retardation). Eight percent had very slow growth over a prolonged period but no definable cause, and 12% did not fall into any of the above groups. For differentiating GHD from CGD, a subnormal height velocity for age during a 4- to 12-month observation period, a low insulin-like growth factor 1/somatomedin C (IGF-1/Sm-C), and low total or free T4, with normal TSH, were all highly predictive of a diagnosis of GHD. PMID- 8001322 TI - Home abatement and blood lead changes in children with class III lead poisoning. AB - We studied the effect of home abatement on blood lead (PbB) levels in children from central Massachusetts who had not undergone chelation therapy and whose homes were abated between 1987 and 1990, when stricter abatement guidelines were enacted. One hundred and thirty-two children with a mean preabatement PbB of 25.9 micrograms/dL (1.25 mumol/L) were studied: their mean postabatement PbB (up to 1 year later) was 21.1 micrograms/dL (1.02 mumol/L) (P < .001). This reduction correlated with preabatement PbB; 32 of 33 (97%) with preabatement PbB > or = 30 micrograms/dL (> or = 1.45 mumol/L) were lower postabatement, and 64 of 79 (81%) with PbB 20 to 29 micrograms/dL (0.97-1.40 mumol/L) were lower. However, in children with preabatement PbB < 20 micrograms/dL (< 0.97 mumol/L), only seven of 20 (35%) were lower postabatement and, in fact, there was a significant rise in PbB from 16.8 to 19.3 micrograms/dL (0.81 to 0.93 mumol/L) (P = 0.05). Continued improvement in home abatement technology is needed if that strategy is to be effective in achieving the lower PbB levels now mandated in the 1991 Centers for Disease Control guidelines. Primary prevention of the initial blood lead level elevation remains the most desirable strategy. PMID- 8001323 TI - Changing pattern of glomerular disease at Beijing Children's Hospital. AB - Current clinical experience with glomerular disease at a pediatric referral center in Beijing, China, was reviewed. In 1992, renal disorders accounted for 505 of a total 6,885 (7.3%) pediatric medical discharges. Acute glomerulonephritis accounted for 30% of renal diagnoses, while nephrotic syndrome accounted for 28% and Henoch-Schonlein purpura nephritis accounted for 16% of renal disease. Mortality in children with renal disease was 0.4% (two of 505). All children with acute glomerulonephritis recovered or improved at last follow up, regardless of the relationship to a streptococcal infection. In children with uncomplicated nephrotic syndrome, 91% had a complete or partial response to corticosteroids. Nephritis developed in 81 of 278 patients with Henoch-Schonlein purpura (29%). Since 1956, a dramatic decrease in the diagnosis of acute glomerulonephritis has occurred at this pediatric hospital. Nephrotic syndrome, in contrast, has increased from 45.3 cases per year in the 1956-to-1965 decade to 146 cases annually in the period from 1986 to 1992. Similarly, Henoch-Schonlein purpura has increased from 45.3 cases annually in the 1956-to-1965 period to 238 cases per year in the past 6 years. The incidence of nephritis in patients with Henoch-Schonlein purpura has remained constant at 29% in the past 36 years. These data should be helpful for individuals and institutions who are planning educational or clinical collaborations with pediatric nephrologists in China. PMID- 8001324 TI - Noonan syndrome. An update and review for the primary pediatrician. PMID- 8001325 TI - The differing presentation of insulin-dependent diabetes mellitus in infants and children. PMID- 8001326 TI - Child abuse by suffocation presenting as hypoxic-ischemic encephalopathy. Report of a patient. PMID- 8001327 TI - Baseline liver function tests following acetaminophen ingestion. What is the utility? PMID- 8001329 TI - Rural health is important to all of Colorado. PMID- 8001328 TI - Dreams happen! PMID- 8001330 TI - X-ray operator rules. PMID- 8001331 TI - Osteoporosis awareness in 1994. PMID- 8001332 TI - Osteoporosis: the state prevention project. PMID- 8001333 TI - [Calcium antagonists in the therapy of arterial hypertension in the aged]. AB - A large number of epidemiologic and interventional studies go to show that acute cerebral and cardiac events and chronic organ injury are significantly less frequent in treated compared to untreated elderly hypertensives. These observations clearly show that hypertension in the elderly must be treated. As to water-electrolyte metabolism, activity of the renin-angiotensin-aldosterone axis as well as volemia are reduced in the elderly while extravascular liquid compartment and activity of the natriuretic atrial factor are both increased. In addition, there is reduction of the baroceptor reflexes accompanied by vasoconstriction and hypertrophy of the smooth muscles associated with increased intracellular calcium ion content. These pathophysiologic conditions appear to supply the rationale for the preference accorded to calcium channel blockers compared to other drugs usually employed in the management of younger hypertensives. Moreover, second generation dihydropyridines, thanks to their liposolubility and ties with calcium channel subunits, show rapid onset and long action that allows for a single daily dose and lowers the incidence of side effects. A large number of interventional trials employing calcium channel blockers have demonstrated the efficacy of these drugs for reducing arterial hypertension. However, these trials concern young hypertensives whereas there is a lack of similar studies in elderly subjects, were clinical trials are few and involve limited numbers of subjects. Results of multicentre studies, at present in progress, will permit to assess the efficacy and incidence of side effects of second generation calcium channel blockers in hypertension of the elderly. PMID- 8001334 TI - [Evaluation of exocrine pancreatic insufficiency in cirrhotic patients,using the fecal chymotrypsin test]. AB - In spite of having been the object of a number of studies, the association of morphologic and functional alterations of the pancreas with liver cirrhosis is as yet controversial. Therefore, the authors have studied exocrine pancreatic function in 40 patients: 8 with alcoholic cirrhosis, 18 with non-alcoholic cirrhosis, and 14 without evidence of hepatobiliary and pancreatic pathology. Pancreatic function was studied by the fecal chymotrypsin test which is sufficiently sensitive and specific and has been preferred in view of its practicability and non-invasiveness. Analysis of the results showed pathologic values to be significantly more frequent in subjects with alcoholic cirrhosis (50%, p < 0.05) compared to non-alcoholic cirrhotics (11.11%) and to controls (7.2%). These findings go to show that pancreatic exocrine deficit is frequently associated with alcoholic cirrhosis, thus confirming what has already been known about the pathogenetic role of alcohol which is apt to provoke both hepatic and pancreatic damage. Finally, it should be pointed out that pancreatic exocrine deficit is a purely functional alteration without clinical manifestations. PMID- 8001335 TI - [Incidence and onset of arterial hypertension and diabetic retinopathy in a population of subjects with diabetes mellitus]. AB - The authors noticed a 50% increase in the incidence of arterial hypertension in diabetic subjects compared with non diabetic ones. Females are more affected in both types of diabetes mellitus and during the first ten years after onset of NIDDM. Diabetic retinopathy is more frequent in IDDM. In hypertensive diabetic females retinopathy is twice as frequent as in non-hypertensive female patients. PMID- 8001336 TI - [Safety of azithromycin in patients allergic to penicillin and cephalosporin]. AB - We have evaluated the safety of a new antibiotic, azithromicin, in 48 patients with allergy to penicillin and/or to cephalosporin. Diagnosis of allergy was based on clinical history, skin test and detection of serum specific IgE. The most common symptoms were urticaria, oedema, pruritus, oral aphthosis. Azithromicin was administered at the increasing dosage of 100-200-300 and 400 mg every 2 days. Our patients did not show any reaction to azithromicin. This antibiotic is therefore a valid alternative to penicillin and/or cephalosporin in patients allergic to these two drugs. PMID- 8001337 TI - [Vitamin E in the aged]. AB - Aging is a multifactorial process still incompletely known. The role of oxidative damage to cell membranes, as an important phase of the process, is underlined by the recent literature. We emphasize the value of vitamin E as an antioxidant agent supplied by suitable diets in middle age and by cheap tablets in the aged. PMID- 8001338 TI - [Hereditary changes of apolipoproteins B and E]. AB - Accelerated atherosclerosis occurs in patients with type III hyperlipoproteinemia and familial hypercholesterolemia. The accumulation of chylomicron remnants of intestinal origin and of VLDL remnants or IDL of hepatic origin observed in type III hyperlipoproteinemia appears to correlate with coronary disease. The presence of defective forms of Apo E prevents normal receptor-mediated catabolism of these lipoproteins. Patients with familial hypercholesterolemia have an elevation of plasma IDL secondary to defective LDL receptors that impair normal catabolism. Familial defective Apo B100 is secondary to an abnormality of Apo B100 that prevents the normal interaction of LDL with the LDL receptor and increases plasma LDL. Macrophages (which are derived from circulating monocytes) have emerged as a key component in atherogenesis because they appear to be progenitors of foam cells in arterial lesions. Macrophages express receptors that recognize chylomicron remnants and VLDL remnants and chemically modified LDL. Thus, in the presence of these specific lipoproteins, macrophages are converted to cells that resemble foam cells. PMID- 8001340 TI - [Computerized tomography and magnetic resonance in the evaluation of patients with Crohn disease. Their role in the identification, assessment of extent and management of the disease]. AB - In this study we evaluated the role of barium examinations and above all computed tomography and magnetic resonance imaging in the study of Crohn's disease. CT is most often requested for patients with suspected or known intraabdominal or pelvic abscesses. MR plays a very important role in the localization of perirectal and perianal abscesses. PMID- 8001341 TI - [Laparoscopy: one of the new landmarks in surgery without the use of the scalpel]. PMID- 8001339 TI - [The role of magnetic resonance in the evaluation of diffuse liver diseases]. AB - We discuss in this report the results and limits of MR imaging in the evaluation of non focal hepatic pathology. At present, MR imaging seems to be one of the most important diagnostic steps, in the study of widespread hepatic diseases. PMID- 8001342 TI - The Reoviridae family. AB - The members of the Reoviridae family are extremely varied in host ranges and have such diverse natural histories that it is compelling to conclude that their structural asset and replication strategy are uniquely successful in evolutionary terms. It follows that their study addresses fundamental aspects of virology, besides the ones which are customary with important pathogens affecting humans, animals and plants. We deal here with the present taxonomy of the family Reoviridae and of its genera, two of which (Orbivirus and Rotavirus) are treated separately in this issue. Along with a cursory presentation of the remaining genera, we give a concise update of recent findings on the genus Orthoreovirus. PMID- 8001343 TI - The orbivirus genus. Diversity, structure, replication and phylogenetic relationships. AB - The general properties of the orbiviruses have been examined at the physical, structural and molecular level. At the structural level, the orbiviruses (with the exception of the Kemerovo serogroup) appear similar. The replicative events are also similar, however differences in the ultrastructure of virus-specific structures and their association with components of the host cell have been observed. Further research in this area may be used to differentiate between the serogroups and even some serotypes, of orbiviruses. At the molecular level the properties of the genome can be used to determine relationships between members of the orbivirus genus. These relationships are revealed using a variety of techniques including serology and gene sequence analysis. Not only are the different serological responses to gene products present in the mature virus particle used for differential diagnosis, but the gene sequences themselves can also be utilized. Understanding of the relationships between these viruses is progressing to the point that insights into orbivirus molecular epidemiology is now possible. PMID- 8001344 TI - The impact of bluetongue virus on reproduction. AB - Bluetongue virus has been recognized as an important noncontagious, arthropodborne infectious viral disease of ruminants. 24 different serotypes of virus have been recognized worldwide. The most severe clinical disease has been associated with severe clinical disease in sheep and some free ranging wild ruminants. A number of reports have implicated the viruses as causing reproductive disorders in both males and females. The bluetongue related reproductive disorders include early embryonic deaths, abortions, malformed fetal calves or lambs, transient infertility in bulls and rams, and shedding of virus in semen. Recently, bluetongue virus contamination of modified live commercial canine vaccine was associated with abortion and acute death of pregnant bitches. The pathogenesis of these various aspects of reproductive failure are discussed herein. PMID- 8001345 TI - The pathogenesis and immunology of bluetongue virus infection of ruminants. AB - Bluetongue (BLU) virus is transmitted from infected to susceptible ruminants by hematophagous vector midges (Culicoides species). Cattle are important reservoir hosts of the virus because infection typically is asymptomatic and characterized by prolonged cell associated viremia, and because at least some species of insect vector preferentially feed on cattle. Interaction of BLU virus with the cell membrane of erythrocytes in infected cattle likely facilitates both prolonged viremia as well as infection of the insect vector. BLU disease is most common in sheep and some wildlife species. A variety of host, agent and environmental factors clearly can influence expression of disease in these species. The pathogenesis of BLU virus infection of cattle and sheep is remarkably similar, thus the basis for expression of disease in sheep but not cattle remains to be firmly established. Some difference in susceptibility of endothelial cells to infection in the two species is one potential explanation. Ruminants develop a variety of antiviral responses after BLU virus infection. Antibodies to outer capsid protein VP2 are responsible for virus neutralization, and confer resistance to reinfection with the homologous serotype of BLU virus. Antibodies to epitopes on proteins which are common to all viruses of the BLU serogroup form the basis of current diagnostic serologic tests. Cell mediated responses have been incompletely characterized, in part because BLU virus replicates within dividing lymphocytes and virus-mediated cytolysis inhibits in vitro blastogenesis. Immunological competence of ruminants to BLU virus arises prior to midgestation, and suggestions that persistent immune tolerant BLU virus infection occurs after in utero exposure of cattle have not been substantiated and are not consistent with recent findings. PMID- 8001346 TI - The epidemiology of bluetongue. AB - The perception that bluetongue virus (BTV), once introduced to a country, would decimate its sheep industry, grew from the acceptance in the late 1950s that it was an emerging virus with Africa as its source. Epidemiological studies in the 1960s and early 1970s confirmed that the geographic distribution of BTV infections included regions of the world, outside the traditionally defined areas where BT was observed. This was interpreted at the time as representing serious and rapid spread of the virus. This review provides evidence to rebut this earlier view. What has emerged through the 1980s is: (a) the recognition that BTV is a common infection of ruminant livestock throughout the tropics and sub tropics apparently within several separate ecosystems; (b) in most areas of the world, infection is sub-clinical; (c) incursions of virus (with accompanying disease) into temperate climates do occur at certain key locations, but "die out" usually within the same year; (d) recognition of the vector competence of Culicoides spp in the different ecosystems of the world is critical for understanding the epidemiology of disease; (e) persistent infection in ruminants is no longer considered important in the long term perpetuation of the virus. PMID- 8001347 TI - Bluetongue: laboratory diagnosis. AB - Definitive diagnosis of bluetongue virus (BTV) infection, often subclinical in domestic and wild ruminant relies heavily on laboratory techniques for BTV isolation and demonstration of BTV antigens, viral nucleic acids and antibodies. The virus can be isolated from blood components, mainly the erythrocyte fraction, collected from affected animals during the period of febrile response. Semen collected from male animals at the peak of viremia and tissues from affected animals and fetuses may also be used for BTV isolation. The primary procedure for BTV isolation is inoculation of embryonated chicken eggs with a subpassage onto cell cultures (e.g. BKH-21, Vero cell lines). In addition to the conventional techniques such as fluorescent antibody staining and virus neutralization procedures for sero-grouping and serotyping of BTV isolates, immunohistochemical, immunoenzymatic and immunoelectron microscopic techniques, using monoclonal antibodies (MAb), offer more rapid, specific and sensitive approaches for BTV identification and antigen detection. The progress of molecular biology, especially the development of genetic probes for hybridization analysis and polymerase chain reaction techniques for detection of BTV nucleic acids hold the promise of most efficient diagnostic assays. Among the various serogroup-specific assays for antibody detection, the agar gel immunodiffusion (AGID) and competitive (C) ELISA are the most widely used tests. Because of its limitations (i.e. anticomplementary serum and complexity of the procedure) the complement fixation (CF) test is virtually abandoned and is used in only a few laboratories. Although the AGID test is simple to perform and rapid, it is not highly sensitive or quantitative and has limitations in its specificity. Sera containing antibodies to other group of Orbiviruses (e.g. epizootic hemorrhagic disease) may result in non-specific reaction in the AGID test. Among several ELISAs that have recently been developed, the C.ELISA in which a group-specific MAb to BTV is used, has proved to be the most sensitive and specific assay for detection of antibodies to BTV. Following extensive national and international validation, the C.ELISA is gradually replacing the AGID as a universal test to certify ruminants for trade purposes and to diagnose BT infection in domestic and wild animals. The cell culture-based microtiter serum neutralization (MTSN) is the most commonly used assay for the detection of serotype-specific antibodies to the recognized BTVs in animal sera. The MTSN may be used to type virus isolates and also to monitor animal population for specific serotypes of BTV in epidemiological investigations. PMID- 8001348 TI - African horse sickness virus structure. AB - African horse sickness virus (AHSV), of which there are nine serotypes (AHSV-1, 2, etc.), is a member of Orbivirus genus within the Reoviridae family. Both in morphology and molecular constituents AHSV particles are comparable to those of bluetongue virus (BTV), the prototype virus of the genus. The two viruses have seven structural proteins (VP1-7) organized in two layered capsid. The outer capsid is composed of VP2 and VP5. The inner capsid, or core, is composed of two major proteins, VP3 and VP7, and three minor proteins, VP1, VP4 and VP6. Within the core is the virus genome. This genome consists of 10 double-stranded (ds)RNA segments of different sizes, three large, designated L1-L3, three medium, M4-M6, and four small, S7-S10. In addition to the seven structural proteins that are coded by seven of the RNA species, four non-structural proteins, NS1, NS2, NS3 and NS3A, are coded by three RNA segments, M5, S8 and S10. The two smallest proteins (NS3 and NS3A) are synthesized by the S10 RNA segment, probably from different in-frame translation initiation codons. Nucleotide sequences of eight RNA segments (L2, L3, M4, M5, M6, S7, S8 and S10) and the predicted amino acid sequences of the encoded gene products are also available, mainly representing one serotype, AHSV-4. In this review the properties of the AHSV genes and gene products are discussed. The sequence and hybridization analyses of the different AHSV dsRNA segments indicate that the segments that code for the core proteins, as well as those that code for NS1 and NS2 proteins, are highly conserved between the different virus serotypes. However, the RNA encoding NS3 and NS3A, and the two segments encoding the outer capsid proteins, are more variable between the AHSV serotypes. A close phylogenetic relationship between AHSV, BTV and epizootic haemorrhagic disease virus (EHDV), three Culicoides-transmitted orbiviruses, has been revealed when the equivalent sequences of genes and gene products are compared. Recently, the four major AHSV capsid proteins have been expressed using recombinant baculoviruses. Biochemically and antigenically these proteins are similar to the authentic proteins. Since the AHSV VP7 protein is highly conserved among the different serotypes, it has been utilized as a diagnostic reagent. The expressed VP7 protein has also been purified to homogeneity and crystallized for three-dimensional X-ray analysis.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8001350 TI - Epizootiology and vectors of African horse sickness virus. AB - African horse sickness (AHS) virus causes a non-contagious, infectious, arthropod borne disease of equines and is enzootic in sub-Saharan Africa. The major vectors are species of Culicoides but mosquitoes and ticks may be involved. Periodically the virus makes excursions beyond its enzootic zones but until recently has not been able to maintain itself outside these areas for more than 2-3 consecutive years. This is probably due to a number of factors including the absence of a long term vertebrate reservoir, the prevalence and seasonal incidence of the vectors and the efficiency of control measures. The recent AHS epizootics in Iberia and North Africa seem to have established a new pattern in AHS virus persistence. This is probably linked to the continuous presence of adult C. imicola in the area. Culicoides imicola is basically an Afro-Asiatic insect and prefers warm climates. Therefore its continuous adult presence in parts of Iberia may be due to some recent moderation of the climate in these areas. PMID- 8001351 TI - Diagnosis of African horsesickness. AB - African horsesickness (AHS) is a very serious, non-contagious disease of horses and other solipeds caused by an arthropod-borne orbivirus of the family Reoviridae. The epizootic nature of the disease makes rapid, accurate diagnosis of AHS absolutely essential. Currently, diagnosis of AHS is based on typical clinical signs and lesions, a history consistent with vector transmission and confirmation by laboratory detection of virus and/or anti-AHS virus antibodies. The clinicopathologic presentation of AHS, current and next generation laboratory diagnostic methods are discussed. PMID- 8001349 TI - African horsesickness: pathogenesis and immunity. AB - African horsesickness (AHS) is a serious, non-contagious disease of horses and other solipeds caused by an arthropod-borne orbivirus of the family Reoviridae. In horses, AHS causes three distinct clinicopathologic syndromes, the pulmonary, cardiac and fever forms of the disease. Recent work has shown that the primary determinant of the form of disease expressed by naive horses is the virulence of the virus inoculum. Horses which recover from AHS exhibit solid humoral immunity against homologous challenge. Protective antibodies appear to be directed towards neutralizing epitopes on AHS virus VP2. The relationship of neutralization to protection and vaccination is discussed. PMID- 8001352 TI - The rotavirus genus. AB - Human rotaviruses, discovered nearly 20 years ago, have been proven to be major cause of paediatric diarrhoeal disease morbidity and mortality. The clinical significance of these viruses stimulated basic studies on their biology, molecular and antigenic properties and epidemiology. General features, clinical relevance, epidemiologic pattern and laboratory diagnosis of human rotavirus infections are here reviewed. PMID- 8001353 TI - A study on neonatal calf diarrhea induced by rotavirus. AB - This review summarizes the results of a study on rotaviruses isolated from calves affected by neonatal diarrhea. The results indicated that rotavirus infection is widespread and supported the evidence for an etiologic role of these viruses in neonatal diarrhea. Differences in virulence among bovine rotaviruses appeared also to be confirmed. Conventionally reared calves were fully susceptible to the experimental infection induced by rotaviruses originating from heterologous hosts, i.e. monkeys, pigs and rabbits. When rotavirus strains of bovine, simian and rabbit origin were compared by cross neutralization tests, it was found the simian and porcine strains were indistinguishable and both appeared to relate antigenically to the bovine strain. Finally, it was proven that feeding newborn calves with colostrum and first milk of their dams, previously vaccinated with an inactivated adjuvanted rotavirus vaccine, could prevent the neonatal diarrhea from occurring. PMID- 8001354 TI - Assessing cause and effect from trials: a cautionary note. PMID- 8001355 TI - Development for and results of the use of a gastroesophageal reflux disease activity index as an outcome variable in a clinical trial. VA Cooperative Study Group on Gastroesophageal Reflux Disease (GERD). AB - Due to the significant expense of obtaining frequent endoscopy and pH monitoring measures as outcome variables available for use in a multihospital clinical trial of gastroesophageal reflux disease, and the lack of a suitable inexpensive index of disease activity, evaluated for both reliability and validity, the study planning committee decided to develop an index of gastroesophageal reflux disease activity in a pilot study--to precede the clinical trial. In particular, the purpose of the pilot study was to find a reliable, valid, and inexpensive index of gastroesophageal reflux disease which could be obtained independently of the treating physician and used as an outcome variable in the clinical trial. This paper describes the pilot study and the statistical methodology used to derive and evaluate a gastroesophageal reflux disease activity index model. In addition, the results of the activity index's use in the subsequent clinical trial's longitudinal analyses are presented. Comparisons with the more expensive, and thus less frequently obtained, endoscopy and pH monitoring outcome variables are described. PMID- 8001356 TI - Simple Bayesian analysis in clinical trials: a tutorial. AB - In this tutorial paper we give a simple Bayesian analysis of data that arise in clinical trials. We consider the case when there are two treatment groups and the response in each group can be assumed to be binomially distributed. We also assume that prior beliefs about the rate parameter in each group can be adequately expressed by a Beta distribution. Using such a model approximate posterior inferences can then be made about the odds ratio between the two groups. We illustrate this methodology by analyzing a randomized trial to assess the benefits of treating patients with carcinoma of the pelvic region (rectum, bladder, colon, cervix) using high-energy fast neutrons as opposed to conventional megavoltage x-rays (photons). In this trial there was prior information about the relative efficacy of neutron therapy based on the beliefs of 10 clinicians. Some of the deficiencies of this simple approach are high lighted and other approaches to analysis indicated. The paper facilitates practical consideration of a Bayesian approach without the complexities that a fuller analysis necessitates. PMID- 8001357 TI - Decision making during a phase III randomized controlled trial. AB - Experiments such as clinical trials should be carried out with specific objectives. For example, in a trial designed to prevent disease, specific considerations should be made concerning the impact of the trial on the health of the target population, including the participants in the trial. These objectives should be assessed continually in light of data accumulating from the trial. Accumulating evidence should be judged in the context of changing circumstances external to the trial, and the trial's design possibly modified. An important type of modification is stopping the trial. This is a sequential decision problem that can be addressed using a Bayesian approach and the methods of dynamic programming. As an example we consider a vaccine trial for the prevention of haemophilus influenzae type b. The objective we consider is minimizing the number of cases of this disease in a Native American population over a specified horizon. We assess the prior probability distribution of vaccine efficacy. We also assess the probability of regulatory approval for widespread use of the vaccine, depending on the data presented to the regulatory officials. In deciding whether to continue the trial we weigh the impact of the possible future results by their (predictive) probabilities. We address the sensitivity of the optimal stopping policy to the prior probability distribution, to the assessed probability of regulatory approval, and to the horizon. PMID- 8001358 TI - The Latin American Multicenter Trial on psychosocial support during pregnancy: methodology and baseline comparability. Latin American Network for Perinatal and Reproductive Research (LANPER). AB - This article presents the methodology and baseline findings of a large multicenter trial involving four countries from Latin America (Argentina, Brazil, Cuba, and Mexico). The study was a randomized, controlled, single-masked trial to investigate the impact of social support during pregnancy on perinatal outcomes. Pregnant women with gestational ages between 15 and 22 weeks were screened in health facilities in the four countries. Those presenting with one or more risk factors for having a low-birthweight baby were invited to join the trial. A total of 2235 women--between 500 and 600 in each country--were randomized into an intervention (n = 1110) or a control (n = 1125) group. Both groups were comparable in terms of nearly all baseline variables. The intervention group received a minimum of four visits at home by a trained health worker who provided direct emotional support, health education, and an attempt to enhance the woman's social support network. Over 90% of all women were evaluated at 36 weeks of pregnancy and soon after delivery, and 85% at the 40th day postpartum. The outcomes under study included intrauterine growth retardation, gestational age, perinatal and maternal morbidity and mortality, labor interventions, psychological distress and characteristics of the social support network, among others. This trial showed that it was possible to select, screen, randomize, visit, and evaluate a large number of women in four Latin American countries using a standardized methodology. PMID- 8001360 TI - The case for confidence intervals in controlled clinical trials. AB - A statistical wit once remarked that researchers often pose the wrong question and then proceed to answer that question incorrectly. The question that researchers intend to ask is whether or not a treatment effect is clinically significant. The question that is typically asked, however, is whether or not the treatment effect is statistically significant--a question that may be only marginally related to the issue of clinical impact. Similarly, the response, in the form of a p value, is typically assumed to reflect clinical significance but in fact reflects statistical significance. In an attempt to address this problem the medical literature over the past decade has been moving away from tests of significance and toward the use of confidence intervals. Concretely, study reports are moving away from "the difference was significant with a p value under 0.01" and toward "the one-year survival rate was increased by 20 percentage points with a 95% confidence interval of 15 to 24 percentage points." By focusing on what the effect is rather than on what the effect is not confidence intervals offer an appropriate framework for reporting the results of clinical trials. This paper offers a non-technical introduction to confidence intervals, shows how the confidence intervals framework offers advantages over hypothesis testing, and highlights some of the controversy that has developed around the application of this method. Additionally, we make the argument that studies which will be reported in terms of confidence intervals should similarly be planned with reference to confidence intervals. The sample size should be set to ensure that the estimates of effect size will be reported not only with adequate power but also with appropriate precision. PMID- 8001359 TI - Echocardiography in multicenter clinical trials: experience from the Treatment of Mild Hypertension Study. AB - Echocardiography is becoming commonplace in clinical trials relating to hypertension for assessing changes in left ventricular mass (LVM). Factors affecting variability need to be considered in the design and management of such studies. These include (1) standardization of recordings and readings, (2) quality of recordings, (3) choice of sonographer vs. cardiologist readers, and (4) reader and temporal variability in measurements. The Treatment of Mild Hypertension Study (TOMHS) provides data and experience concerning these issues. TOMHS was a randomized trial of 902 participants, men and women, conducted in four clinical centers comparing six treatments for mild hypertension. M-mode echocardiograms were recorded at baseline and follow-up by centrally trained sonographers for assessment of LVM. Initial study design specified that each tracing be read by two sonographers with a study cardiologist adjudicating major differences in measurements. Poor agreement between sonographer readings prompted a change in design requiring one of two study cardiologists to read all tracings, with the same cardiologist reading all serial studies for a participant. Common tracings were read to assess interreader variability. The percentage of unreadable tracings varied by center (0.4-14.2%) and increased over follow-up. Reader agreement between the two cardiologists for LVM was greater (r = 0.83) than between sonographers (r = 0.68) or between sonographers and cardiologists (r = 0.64). The agreement between sonographer and cardiologist readings varied by center (range of r = 0.54-0.81), the highest correlations being in the two centers with physician echocardiographers. The intraclass correlation across visits for LVM was 0.66, being similar for all visit pairs. The standard deviation of the difference between baseline and follow-up LVM was 46 g using cardiologist readings, 51 g for readings made by the same sonographer, and 68 g for readings made by different sonographers, a difference that is large enough to appreciably affect sample size and power for studies. High-quality echocardiographic data can be obtained in multicenter trials, but this requires the continued training of sonographers and readers and ongoing monitoring of quality of tracings and measurements. PMID- 8001361 TI - Can catabolism be reversed and survival enhanced by altering glucose, somatostatin, and glucagon levels in systemically ill patients? PMID- 8001362 TI - Progressive magnesium deficiency increases mortality from endotoxin challenge: protective effects of acute magnesium replacement therapy. AB - OBJECTIVES: To study the effects of endotoxin on magnesium homeostasis; to determine if progressive magnesium deficiency alters outcome from endotoxin challenge; and to evaluate the efficacy of magnesium therapy in reducing endotoxin-induced mortality. DESIGN: Prospective, placebo-controlled, randomized, multiexperiment studies. SETTING: Research laboratory of a university hospital. SUBJECTS: Male Sprague Dawley rats (n = 299). INTERVENTIONS: Experiment 1 was designed to test if endotoxin alters magnesium homeostasis. Circulating total and ionized magnesium (estimated by ultrafilterable values) concentrations were determined in blood samples collected from animals after the randomized administration of placebo or 0.3, 3.0, or 30 mg/kg of endotoxin. A baseline blood sample was collected and then a second blood sample was obtained at 5, 15, 30, 60, 120, or 180 mins after endotoxin or placebo administration. In experiment 2, animals were randomized to receive magnesium-sufficient diets or magnesium deficient diets for 6 wks. After 6 wks, the effects of the randomized administration of 3.0 mg/kg endotoxin or placebo were evaluated on mortality and analyte values (pH and blood gases, sodium, potassium, chloride, glucose, ionized calcium, hematocrit, total and ultrafilterable magnesium concentrations) in the three study groups (magnesium-sufficient, 3-wk magnesium-deficient, or 6-wk magnesium-deficient). In experiment 3, magnesium-deficient animals were randomized to receive 50 mmol/kg magnesium chloride or placebo, before or after the administration of 3.0 mg/kg of endotoxin. Baseline and 24-hr analyte determinations were performed and outcome was analyzed. MEASUREMENTS AND MAIN RESULTS: Experiment 1: Significant increases (p < .05) in circulating total magnesium concentrations were found in animals that received 30 mg/kg of endotoxin, at 120 mins (0.79 +/- 0.10 vs. 0.60 +/- 0.05 mmol/L), and 180 mins (0.74 +/- 0.04 vs. 0.56 +/- 0.04 mmol/L) compared with baseline values. Similarly, significant increases (p < .05) in ionized magnesium concentrations were observed 120 and 180 mins after 3.0 and 30 mg/kg of endotoxin compared with baseline values. Experiment 2: Magnesium deficiency was strongly (p < .02) associated with increased mortality from endotoxin challenge. Endotoxin administration (3.0 mg/kg) was lethal in 10 (43%) of 23 magnesium-sufficient animals, 15 (65%) of 23 3-wk magnesium-deficient animals, and 20 (83%) of 24 6-wk magnesium-deficient animals. Experiment 3: In magnesium-deficient animals, rats treated with magnesium replacement therapy had significantly increased survival from endotoxin administration (15 [52%] of 29 vs. five [17%] of 29, p < .01) compared with placebo-treated animals. CONCLUSIONS: a) Endotoxin challenge causes significant increases in circulating total and ionized magnesium concentrations. b) Progressive magnesium deficiency is strongly associated with increased lethality, and magnesium replacement therapy provides significant protection from endotoxin challenge. c) These experimental results support the concept that cellular injury is probably associated with increases in circulating magnesium concentrations. Furthermore, these experimental findings suggest that magnesium deficiency predisposes to worse outcome from endotoxin challenge, and that replacement therapy in the setting of magnesium deficiency may be warranted, especially in critically ill subjects. PMID- 8001363 TI - Pentoxifylline does not prevent microvascular injury in normotensive, septic rats. AB - OBJECTIVE: To determine if treatment with pentoxifylline would decrease the tissue injury that occurs in a normotensive model of sepsis. DESIGN: Random assignment to control, cecal ligation-perforation, or cecal ligation-perforation plus pentoxifylline groups for a 24-hr study. SETTING: Animal laboratory. SUBJECTS: Male Sprague-Dawley rats. INTERVENTIONS: Sepsis was induced by cecal ligation-perforation with aggressive fluid resuscitation (normal saline 10 mL/kg/hr). Pentoxifylline was administered as a 2-mg/kg bolus, followed by a continuous infusion of 6 mg/kg/hr. MEASUREMENTS AND MAIN RESULTS: Compared with controls, rats in the cecal ligation-perforation group had an increased heart rate (432 +/- 12 vs. 399 +/- 10 beats/min) and respiratory rate (129 +/- 6 vs. 94 +/- 7 breaths/min). Blood pressure was slightly decreased (104 +/- 4 vs. 125 +/- 5 mm Hg), while cardiac index was not significantly different (50.1 +/- 5.7 vs. 40.7 +/- 3.9 mL/min/100 g). Blood pressure (103 +/- 4 mm Hg) was the only parameter that was significantly different in the cecal ligation-perforation plus pentoxifylline group compared with controls. When compared with controls, tissue wet/dry weight ratios were increased in the diaphragm of the cecal ligation perforation group and in the liver, pancreas, small bowel, and large bowel of the cecal ligation-perforation, and the cecal ligation-perforation plus pentoxifylline groups. Tissue/plasma albumin ratios were increased in the diaphragm of the cecal ligation-perforation group and in the liver, pancreas, and large bowel of the cecal ligation-perforation and the cecal ligation-perforation plus pentoxifylline groups. There were no significant differences between the cecal ligation-perforation and the cecal ligation-perforation plus pentoxifylline groups. CONCLUSIONS: Normotensive sepsis is accompanied by increased vascular permeability in the diaphragm and intra-abdominal organs. Pentoxifylline appears to attenuate some of the systemic manifestations of sepsis. However, pentoxifylline did not prevent the development of protein-rich tissue edema. PMID- 8001364 TI - Calcium and phospholipase A2 appear to be involved in the pathogenesis of hemorrhagic shock-induced mucosal injury and bacterial translocation. AB - OBJECTIVE: The mechanism by which hemorrhagic shock injures the gut and leads to the translocation of bacteria remains incompletely determined. Since increased free cellular calcium levels and phospholipase A2 activity can lead to cellular injury and both have been documented in certain shock states, the hypothesis that calcium or phospholipase A2 may play a role in hemorrhagic shock-induced gut mucosal injury and bacterial translocation was tested. DESIGN: Prospective animal study with concurrent controls. SETTING: Small animal laboratory. SUBJECTS: Fifty seven male Sprague-Dawley rats weighing 250 to 350 g. INTERVENTIONS: Five groups of rats were tested utilizing a nonlethal hemorrhagic shock model (mean arterial pressure of 30 mm Hg for 30 mins). These groups included: a) sham-shock, b) shock, c) shock plus quinacrine (inhibitor of phospholipase A2), d) shock plus diltiazem (calcium-channel blocker) administered 5 mins before hemorrhage, and e) shock plus diltiazem administered at the end of shock period and before resuscitation. At 24 hrs postshock or sham-shock, the animals were killed, the mesenteric lymph node and cecum were cultured and the gut was examined histologically. MEASUREMENTS AND MAIN RESULTS: The occurrence rate of shock induced bacterial translocation (90%) was significantly reduced in rats receiving quinacrine (27%) or preshock diltiazem (21%) (p < .05), but not postshock diltiazem (63%). Bacterial translocation did not occur in sham-shocked rats. The same amount of blood withdrawal was needed between all groups of rats to induce and maintain shock. Quinacrine and diltiazem administration largely prevented shock-induced ileal and cecal mucosal injury. CONCLUSIONS: The observation that quinacrine and preshock diltiazem limited the extent of shock-induced mucosal injury and bacterial translocation indicate that calcium and phospholipase A2 are involved in the pathogenesis of shock-induced mucosal injury and bacterial translocation. The fact that preshock but not postshock diltiazem was protective indicates that the process leading to shock-induced calcium-mediated tissue injury and bacterial translocation was initiated during the ischemic rather than the reperfusion period. However, since neither quinacrine nor diltiazem was fully protective, other factors, such as oxidants, are also likely to be involved in the pathogenesis of shock-induced mucosal injury and bacterial translocation. PMID- 8001365 TI - Effects of treatment with the 21-aminosteroid, U7438F, on pulmonary cytokine expression following hemorrhage and resuscitation. AB - OBJECTIVE: To determine the effects of therapy with the antioxidant 21 aminosteroid, U74389F, on cytokine mRNA levels following hemorrhage and resuscitation. DESIGN: Prospective, controlled animal study. SETTING: University research laboratory. SUBJECTS: Male bronchoalveolar lavage B/c (BALB/c) mice. INTERVENTIONS: U74389F (10 mg/kg) in CS4 vehicle or CS4 vehicle alone, was administered intravenously to bronchoalveolar lavage B/c mice 15 mins before 30% blood volume hemorrhage, with resuscitation 60 mins later. MEASUREMENTS AND MAIN RESULTS: Semiquantitative polymerase chain reactions were used to determine the effects of therapy with U74389F on cytokine mRNA levels among intraparenchymal pulmonary mononuclear cells, alveolar macrophages, and peripheral blood mononuclear cells obtained 2 hrs and 3 days after hemorrhage. In mice treated with U74389F, mRNA levels for interleukin (IL)-1 beta, IL-6, IL-10, tumor necrosis factor-alpha, and interferon-gamma were significantly decreased among intraparenchymal pulmonary mononuclear cells obtained 3 days, but not 2 hrs, after hemorrhage. No effects of therapy with U74389F were found in modulating posthemorrhage cytokine expression among alveolar macrophages or peripheral blood mononuclear cells. CONCLUSIONS: These studies demonstrate that treatment with U74389F, a 21-aminosteroid whose major activity is inhibition of lipid peroxidation due to the generation of reactive oxygen intermediates, significantly decreases hemorrhage-induced activation of proinflammatory cytokine expression among pulmonary cell populations. In addition, the present results, showing decreased expression of proinflammatory and immunoregulatory cytokines among intraparenchymal pulmonary mononuclear cells following treatment with U74389F, suggest that 21-aminosteroids may have clinical utility in preventing and/or modulating acute lung injury in the postinjury period. PMID- 8001366 TI - Surfactant replacement reverse respiratory failure induced by intratracheal endotoxin in rats. AB - OBJECTIVE: To evaluate the effect of surfactant replacement on respiratory failure induced by intratracheal injection of endotoxin in rats. DESIGN: Prospective, randomized study. SETTING: Laboratory at a large university. SUBJECTS: Male Wistar rats, weighing 353 +/- 50 (SD) g. INTERVENTIONS: Escherichia coli endotoxin (53 +/- 19 mg/kg) was injected into the trachea of 32 rats anesthetized with pentobarbital and mechanically ventilated with an FIO2 of 1.0. After PaO2 decreased to < 200 torr (< 26.7 kPa), the rats were assigned to three groups: a) a surfactant group (n = 16), given a modified natural surfactant suspension (100 mg/kg in 2.0 mL/kg of saline) by instillation into the airway; b) a saline control group (n = 8), given 2.0 mL/kg of saline; and c) an air control group (n = 8), given 2.0 mL/kg of air. An additional nine rats were ventilated in the same way but were not given endotoxin. MEASUREMENTS AND MAIN RESULTS: Among the rats receiving endotoxin, the PaO2 of the saline and air control groups remained < 200 torr (< 26.7 kPa), while PaO2 of the surfactant group increased to 390 +/- 116 torr (52.0 +/- 15.5 kPa; p < .05 vs. the preassignment value) 15 mins after the assignment. These high levels were maintained throughout the experiment. Surfactant replacement also led to significant improvements in the PaCO2, the dynamic lung-thorax compliance, the pressure-volume recordings of the lung, and the chest roentgenograms. Histologic examination showed that the alveoli of the surfactant group were better aerated than the alveoli of the control groups. Findings in the rats not given endotoxin were almost normal, indicating that the influences of mechanical ventilation were negligible. CONCLUSION: Surfactant replacement reversed respiratory failure induced by intratracheal injection of endotoxin in rats. PMID- 8001367 TI - Development and application of a simplified liquid ventilator. AB - OBJECTIVE: Perfluorocarbon liquid ventilation has been shown to have advantages over conventional gas ventilation in premature newborn and lung-injured animals. To simplify the process of liquid ventilation, we adapted an extra-corporeal life support circuit as a time-cycled, volume-limited liquid ventilator. DESIGN: Laboratory study that involved sequential application of gas and liquid ventilation in normal cats and in lung-injured sheep. SETTING: A research laboratory at a university medical center. SUBJECTS: Eight normal cats weighing 2.7 to 3.8 kg (mean 3.1 +/- 0.5), and four lung-injured young sheep weighing 10.4 to 22.5 kg (mean 15.9 +/- 5.0). INTERVENTIONS: Normal cats were supported with traditional gas ventilation for 1 hr (respiratory rate 20 breaths/min, peak inspiratory pressure 12 cm H2O, positive end-expiratory pressure 4 cm H2O, and FIO2 1.0). The lungs were then filled with perfluorocarbon (30 mL/kg) and tidal volume liquid ventilation was instituted, utilizing a newly developed liquid ventilation device. Liquid ventilatory settings were 4 secs for inspiration time, 8 secs for expiration time, 5 breaths/min for respiratory rate, and 15 to 20 mL/kg for tidal volume. Liquid ventilation utilizing this device was also applied to sheep after induction of severe lung injury by right atrial injection of 0.07 mL/kg of oleic acid, followed by saline pulmonary lavage. Extracorporeal life support was instituted to provide a stable model of lung injury. For the first 30 mins of extracorporeal support, all animals were ventilated with gas. Animals were then ventilated with 15 mL/kg of perfluorocarbon over the ensuing 2.5 hrs. MEASUREMENTS AND MAIN RESULTS: In normal cats, mean PaO2 values after 1 hr of liquid or gas ventilation were 275 +/- 90 (SD) torr (36.7 +/- 10.4 kPa) in the liquid-ventilated animals and 332 +/- 78 torr (44.3 +/- 10.4 kPa) in the gas ventilated animals (NS). Mean PaCO2 values were 40.5 +/- 5.7 torr (5.39 +/- 0.31 kPa) in the liquid-ventilated animals and 37.6 +/- 2.3 torr (5.01 +/- 0.31 kPa) in the gas-ventilated animals (NS). Mean arterial pH values were 7.35 +/- 0.07 in the liquid-ventilated animals and 7.34 +/- 0.04 in the gas-ventilated animals (NS). No significant changes in heart rate, mean arterial pressure, lung compliance, or right atrial venous oxygen saturation were observed during liquid ventilation when compared with gas ventilation. In the lung-injured sheep, an increase in physiologic shunt from 15 +/- 7% to 66 +/- 9% was observed with induction of lung injury during gas ventilation. Liquid ventilation resulted in a significant reduction in physiologic shunt to 31 +/- 10% (p < .001). In addition, the extracorporeal blood flow rate required to maintain the PaO2 in the 50 to 80 torr (6.7 to 10.7 kPa) range was substantially and significantly (p < .001) lower during liquid ventilation than during gas ventilation (liquid ventilation 15 +/- 5 vs. gas ventilation 87 +/- 15 mL/min/kg). CONCLUSIONS: Liquid ventilation can be performed successfully utilizing this simple adaptation of an extracorporeal life-support circuit. This modification to an existing extracorporeal circuit may allow other centers to apply this new investigational method of ventilation in the laboratory or clinical setting. PMID- 8001368 TI - Effect of graded increases in smoke inhalation injury on the early systemic response to a body burn. AB - OBJECTIVE: To study the early (first 24 hrs) effect of increasing lung exposure to smoke on the hemodynamic response to a modest body burn. DESIGN: A prospective randomized study. SETTING: Laboratory at a university medical center. SUBJECTS: Thirty-two adult yearling female sheep. INTERVENTIONS: Adult sheep (n = 32) were given an 18% of body surface burn; 24 sheep were then exposed to cotton toweling smoke using 12 breaths of a tidal volume of 5, 10, or 20 mL/kg. Animals were awakened, resuscitated to baseline oxygen delivery, and then killed at 24 hrs. MEASUREMENTS AND MAIN RESULTS: Vascular pressure, cardiac output, and oxygen consumption and delivery were measured, as well as blood gases, lung and soft tissue lymph flow, and fluid balance. We found that a 5-mL/kg tidal volume smoke exposure x 12 breaths did not produce significant airway inflammation or alter the cardiopulmonary response to a burn alone. Oxygen consumption (VO2) remained at baseline and the net 24-hr positive fluid balance of 1.5 L was comparable to a burn alone. Increasing the smoke exposure to 10 mL/kg tidal volume, which produced a moderate airway injury, resulted in a significant increase in early fluid requirements, a 40% early increase in VO2, a doubling of positive fluid balance, as well as a marked increase in burn edema. However, gas exchange was not impaired. The 20-mL/kg tidal volume exposure resulted in an early 100% increase in VO2, a three-fold increase in fluid requirements at 1 to 4 hrs, compared with burn alone, in addition to a severe airway inflammation with mucosal slough and resulting impaired gas exchange. CONCLUSIONS: The addition of a smoke exposure which produces airway inflammation and injury significantly increases early post burn systemic metabolic demands and fluid requirements, as well as the degree of burn edema and positive fluid balance compared with a burn alone. The magnitude of the accentuated response appears to correspond with the degree of airway inflammation and not with alveolar dysfunction. PMID- 8001369 TI - Effect of ductal patency on organ blood flow and pulmonary function in the preterm baboon with hyaline membrane disease. AB - OBJECTIVE: To examine the effect of early ductal ligation vs. maintenance of ductal patency on vital organ perfusion and pulmonary function in premature baboons with hyaline membrane disease. DESIGN: Randomized, controlled interventional study to compare early ligation with formalin infiltration of the ductus arteriosus. SETTING: Animal care facility at a dedicated research foundation. SUBJECTS: Eighteen premature baboons delivered by hysterotomy at 140 +/- 2 day gestation. INTERVENTION: Nine premature baboons underwent formalin infiltration of the ductus arteriosus (group 1), and nine underwent ductal ligation (group 2). Surgical ligation or formalin infiltration was performed at 2 to 4 hrs of age. Animals were maintained on mechanical ventilation and ventilator parameters were adjusted to maintain PaO2 and PaCO2 within the physiologic range. MAIN OUTCOME MEASURES: Left ventricular output indexed to body weight and vital organ perfusion were measured at 24 hrs of age by the radiolabeled microsphere method. Lung mechanics, including lung wet/dry weight ratio, total lung water, static compliance and functional residual capacity were measured immediately following euthanasia. RESULTS: Total pulmonary blood flow was significantly lower (p = .0001) in group 2 (mean = 94 mL/min/kg), compared with group 1 (mean = 287 mL/min/kg). Systemic blood flow and effective pulmonary blood flow were higher in group 1 (p = .07). No significant difference between groups in absolute organ blood flow was noted, although flow as a percent of left ventricular index was significantly higher in all organs except the kidney in group 2. There was no difference in arterial blood gas values, parameters of mechanical ventilation, percent lung water, or postmortem measurement of lung mechanics between groups. CONCLUSION: Early ductal ligation did not result in improved cardiac output, increased organ blood flow, or improved pulmonary function. We postulate that gradual constriction of the ductus arteriosus may play an important role in successful cardiovascular adaptation in the premature infant. While it is clear that premature infants with symptomatic patent ductus arteriosus often benefit from ductal closure, we question the practice of prophylactic early ductal closure. PMID- 8001370 TI - Old age does not negate good cerebral outcome after cardiopulmonary resuscitation: analyses from the brain resuscitation clinical trials. The Brain Resuscitation Clinical Trial I and II Study Groups. AB - OBJECTIVE: To assess survival after cardiac arrest and to determine whether age is an independent determinant of late mortality or poor neurologic outcome. DESIGN: Analyses using results of Brain Resuscitation Clinical Trial I (1979 to 1984) and Brain Resuscitation Clinical Trial II (1984 to 1989), two randomized, double-blind studies of outcome following cardiac arrest. SETTING: A multicenter study in 12 acute care hospitals in nine countries (Brain Resuscitation Clinical Trial I), and 24 hospitals in eight countries (Brain Resuscitation Clinical Trial II). PATIENTS: A total of 774 patients who were initially comatose after successful resuscitation from cardiac arrest. The analyses include both in- and out-of-hospital cardiac arrests. RESULTS: The 6-month mortality rate for the entire group was 81%. Mortality rate was 94% for the oldest group (> 80 yrs) compared with 68% for the youngest group (< or = 45 yrs) (p < .01). Other independent predictors of mortality were history of diabetes mellitus, inhospital arrests, arrest time of > 5 mins, history of congestive heart failure, a noncardiac cause of arrest, and cardiopulmonary resuscitation time of > 20 mins. Of the 774 patients, 27% recovered good neurologic function. There was no statistically significant difference in neurologic recovery rates by age. Multivariate analysis showed that independent predictors of good neurologic recovery were: no history of diabetes mellitus, a cardiac cause of arrest, short arrest time, and short cardiopulmonary resuscitation time. CONCLUSION: Increasing age was a factor in postresuscitation mortality, but was not an independent predictor of poor neurologic outcome. PMID- 8001371 TI - Accuracy of disposable blood pressure transducers used in the critical care setting. AB - OBJECTIVES: To assess the initial accuracy, drift in calibration over several hours, and decline in accuracy over daily use of blood pressure transducers used in the critical care setting. DESIGN: Prospective, criterion standard. SETTING: Three critical care units in a university hospital. SUBJECTS: Twenty-seven consecutively available high-pressure transducers were used to measure intra arterial blood pressures, and 11 consecutively available low-pressure transducers were used to measure central venous and pulmonary arterial blood pressures. INTERVENTIONS: High-pressure transducers were compared with a mercury column manometer, and low-pressure transducers were compared with a water column manometer at three pressure levels. Data were collected initially after installation of the pressure transducer, at 3 hrs, and at 6 hrs. Data collections were repeated on subsequent days. MEASUREMENTS AND MAIN RESULTS: a) The majority of pressure transducers are accurate; b) there is no drift in the accuracy of pressure transducers over several hours; c) the accuracy of pressure transducers does not decline over subsequent days. Some transducers over-estimated standard pressures by 10 mm Hg and/or underestimated standard pressure by 17 mm Hg. CONCLUSIONS: The majority of pressure transducers used in the critical care setting are accurate, although there are some transducers that may compromise patient care. Blood pressure transducers should be checked against a standard manometer upon installation, and daily during use. PMID- 8001372 TI - Reversal of hepatorenal syndrome with the combination of norepinephrine and dopamine. PMID- 8001373 TI - Progressive respiratory insufficiency after cesarean section. PMID- 8001374 TI - Esophageal obstruction secondary to concretions of tube-feeding formula. PMID- 8001375 TI - Delivery-dependent oxygen consumption: what was the question? PMID- 8001376 TI - Sudden death in a patient given esmolol. PMID- 8001377 TI - Endotoxemia and liver transplantation. PMID- 8001378 TI - Inspiratory load increases inspiratory time. PMID- 8001379 TI - Continuous infusions of haloperidol in critically ill patients. PMID- 8001380 TI - Pediatric veno-venous hemofiltration. PMID- 8001381 TI - Pediatric veno-venous hemofiltration. PMID- 8001382 TI - Circulating interleukin-1 receptor antagonist concentrations are increased in adult patients with thermal injury. AB - OBJECTIVE: To investigate the balance between circulating concentrations of interleukin (IL)-1 and its natural inhibitor interleukin-1 receptor antagonist (IL-1Ra) in human inflammation. DESIGN: Prospective case-control study. SETTING: University hospital burn care unit. PATIENTS: Fifteen patients with second- or third-degree thermal injuries of 7% to 78% of total body surface and 15 healthy age- and sex-matched control subjects. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Median plasma IL-1Ra, but not IL-1 beta or tumor necrosis factor-alpha (TNF-alpha) concentrations were markedly increased on the day of admission in patients with thermal injuries compared with controls (1615 [range 426 to 23,800] vs. 494 [range 196 to 1093] pg/mL; p < .001). In survivors, the median IL-1Ra concentration normalized 12 to 21 days after admission. The concentration of IL 1Ra on the day of admission was weakly positively correlated to the extent and degree of thermal injury (r2 = .46; p < .05). IL-1Ra on days 1 to 3 was highest in three nonsurvivors with inhalation injuries compared with survivors (2166 [range 1362 to 36,624] vs. 1344 [range 665 to 13,085] pg/mL; p < .05). IL-1Ra increased significantly after debridement and skin transplantation (preoperatively 742 [range 488 to 1506] vs. postoperatively 1431 [range 1286 to 2107] pg/mL; p < .01). In nonsurvivors, median IL-1Ra was 3.6-fold higher than IL 1 beta on days 1 to 2 and 36-fold higher than IL-1 beta in three patients with bacteremia. IL-1Ra was studied for its relationship to previously reported parameters of the acute-phase response determined in the same samples from these patients. The increased concentrations of IL-1Ra coincided with a decrease in serum albumin concentration and increases in rectal temperature. However, IL-1Ra did not correlate with rectal temperature, plasma concentrations of endotoxin, IL 1 beta, or TNF-alpha either at admission or in follow-up samples. CONCLUSIONS: Thermal injury causes an increase of circulating IL-1Ra, especially in patients with inhalation injuries. With the current plasma assays for IL-1 beta, IL-1Ra may be a more sensitive marker of human inflammation than IL-1 beta or TNF-alpha. PMID- 8001383 TI - Endocrine tea leaves: validity of a hormonal profile in predicting patient outcome. PMID- 8001384 TI - Endothelin-1 increases intracellular calcium in human monocytes and causes production of interleukin-6. AB - OBJECTIVE: To define whether endothelin-1, a peptide produced by injured/ischemic endothelium, has any effect on monocyte intracellular calcium and the production of interleukin (IL)-1 and IL-6. DESIGN: Prospective controlled laboratory study. Human monocytes from healthy donors were assayed for intracellular calcium by fluorometry and were stimulated for 24 hrs in tissue culture with purified endotoxin or endothelin. SETTING: Veterans Affairs Medical Center surgical critical care basic science laboratory. MEASUREMENTS AND MAIN RESULTS: Endothelin 1 increased the intracellular calcium concentration in fura-2 loaded human monocytes to a mean value of 37 +/- 4 nmol. Phytohemagglutinin increased intracellular calcium in control monocytes to a mean value of 97 +/- 12 nmol (n = 15; p < .001). Endothelin had no effect on neutrophil or lymphocyte intracellular calcium. Monocytes incubated with 10(-9) M endothelin significantly increased IL 6 production to values nearly as high as the lipopolysaccharide controls, but did not increase IL-1 production (n = 8; p < .01). CONCLUSION: Endothelin-1 increased intracellular calcium in monocytes and caused production of IL-6. PMID- 8001385 TI - Fluid resuscitation in brain-injured patients. PMID- 8001386 TI - Femoral deep vein thrombosis associated with central venous catheterization: results from a prospective, randomized trial. AB - OBJECTIVE: To determine the frequency of central venous catheter-induced deep vein thrombosis of the femoral vein. DESIGN: Prospective, randomized, controlled trial. SETTING: Tertiary care center. PATIENTS: Forty-five patients in a medical surgical intensive care unit who required central venous catheterization. INTERVENTIONS: Patients were randomized to receive central venous catheterization in either upper (subclavian or internal jugular veins) or lower (femoral vein) catheterization sites. Lower extremity duplex ultrasound examinations were performed before central venous catheter placement, after removal of the catheter, and 7 days after catheter removal. Ultrasound examinations were reported as positive, nondiagnostic, or negative for deep vein thrombosis. MEASUREMENTS AND MAIN RESULTS: Of the 21 patients randomized to upper access sites, none developed positive or nondiagnostic duplex ultrasound examinations. Six (25%) of 24 patients randomized to the femoral access site developed lower extremity deep vein thrombosis (p = .02). In addition, seven (29%) patients randomized to the lower access site sustained non-diagnostic ultrasound examinations. A total of 13 (54%) of 24 patients from the lower access group developed abnormal ultrasound examinations (p < .001). Age, duration of catheterization, coagulation profile, deep vein thrombosis prophylaxis, and Acute Physiology and Chronic Health Evaluation II scores were similar between the upper and lower access groups. CONCLUSIONS: Based on the data from this study, we concluded that femoral vein catheterization is associated with a 25% frequency of lower extremity deep vein thrombosis compared with similar patients receiving subclavian or internal jugular vein catheters. The femoral vein remains an important emergency venous access route. Physicians inserting femoral vein catheters should be aware of the risk of lower extremity deep vein thrombosis and should consider performing lower extremity duplex ultrasound examinations on removal of femoral vein catheters. PMID- 8001387 TI - Facilitation of internal jugular venous cannulation using an audio-guided Doppler ultrasound vascular access device: results from a prospective, dual-center, randomized, crossover clinical study. AB - OBJECTIVE: To determine the utility of an audio-guided Doppler ultrasound device in improving success and decreasing complications in cannulation of the internal jugular vein in high-risk patients. DESIGN: Prospective, randomized, crossover clinical study. SETTING: Two major university medical centers in critical care environments. PATIENTS: Seventy-six consecutive, consenting adult patients with preexisting obesity or coagulopathy requiring central venous access. INTERVENTIONS: Subjects enrolled in the study were randomized to receive either the traditional "blind" (control) technique or the ultrasonic technique. A maximum of three cannulation attempts were allowed before crossover to three attempts with the alternative technique. All cannulations were attempted via the internal jugular vein through a high/central approach. RESULTS: Patient and operator characteristics were similar between groups. The initial use of an audio guided ultrasound device was associated with increased success of cannulation (84.4% vs. 61.4%; p < .05) and decreased need to crossover to the alternative technique. Success on the first needle pass was more likely with the ultrasound technique (56.3% vs. 29.5%; p < .05). Significant complications were greater with the control technique (carotid artery puncture 16.3% vs. 2.0% [p < .02]; any significant complication 26.5% vs. 6.1% [p < .01]). CONCLUSIONS: The use of an audio-guided Doppler ultrasound vascular access device was associated with increased success of cannulation and a decreased frequency of significant complications in a population of high-risk patients with obesity or coagulopathy. PMID- 8001389 TI - Systemic cardiovascular changes with acute lung injury. PMID- 8001388 TI - Estimated cerebral metabolic rate of oxygen in severely brain-injured patients: a valuable tool for clinical monitoring. AB - OBJECTIVE: To evaluate a novel parameter of global cerebral oxygen metabolism, the estimated cerebral metabolic rate of oxygen, for its clinical utility in monitoring acute, severely brain-injured patients. DESIGN: Prospective, observational study. SETTING: Neuroscience intensive care unit of a university hospital. PATIENTS: Sixty-six adults with acute brain trauma undergoing 133Xe regional cerebral blood flow and global cerebral oxygen metabolic studies, in conjunction with other routine monitoring techniques. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Estimated cerebral metabolic rate of oxygen was calculated as the product of PaCO2 and arterio-jugular oxygen content difference, and compared with the measured cerebral metabolic rate of oxygen (the product of mean regional cerebral blood flow and arterio-jugular oxygen content difference). Good correlations were found between the estimated and the true values (r2 = .56/.67, p < .0001) in 91 studies performed in 66 patients. CONCLUSIONS: These findings suggest that the estimated cerebral metabolic rate of oxygen is a useful substitute for the traditional cerebral metabolic rate of oxygen when cerebral blood flow information is not available. In addition, with this parameter, the patient's metabolic status can be assessed more frequently than with cerebral blood flow studies. These measurements do not require special instrumentation and can be done in any intensive care setting. PMID- 8001390 TI - Manipulation of substrate utilization with somatostatin in patients with secondary multiple organ dysfunction syndrome. AB - OBJECTIVES: To determine whether glucose utilization and metabolic substrate (glucose and fat) oxidation could be manipulated in patients with secondary multiple organ dysfunction syndrome. DESIGN: Prospective study. SETTING: Intensive care units (ICU) of two university hospitals. PATIENTS: Eight adults free of hepatic disease and hemodynamically stable at the time of study, but with failed respiratory and gastrointestinal systems, who thus required mechanical ventilation and intravenous nutrition. INTERVENTIONS: Patients were infused with 20% dextrose through central venous cannulas at rates that increased and maintained (clamped) their plasma glucose concentration at 216 mg/dL (12 mmol/L) for 3 hrs. Somatostatin was infused continuously during the second and third hours of the clamp to reduce plasma concentrations of endogenous insulin and glucagon. Exogenous insulin was administered together with somatostatin during the third hour to restore basal insulin concentrations. Energy expenditure was measured by indirect calorimetry throughout the study and blood samples were withdrawn regularly for determination of metabolite and hormone concentrations. Main statistical comparisons were made between the baseline data (first hour of the study) and data collected during the second and third hours of the clamp. MEASUREMENTS AND MAIN RESULTS: Plasma glucagon concentrations were reduced by nearly 50% (p < .05) toward the end of the study, whereas no significant changes in plasma concentrations of cortisol or growth hormone occurred. Energy expenditure did not change significantly at any time during the clamp procedure. Glucose utilization (6.1 mg/kg/min [34 mumol/kg/min]) during the first hour of the hyperglycemic clamp, decreased by 53% (p < .05) with the infusion of somatostatin during the second hour of the clamp. However, once exogenous insulin was infused during the third hour, glucose utilization increased by 55% (p < .05) when compared with the baseline (hour 1) rate. Glucose oxidation was nearly doubled during the third hour of the study when compared with oxidation rates during the first and second hours. Fat oxidation decreased steadily during the 3 hr clamp. CONCLUSIONS: Glucagon has a significant inhibitory effect on glucose utilization during intravenous glucose infusion in the multiple organ dysfunction syndrome patient. Pharmacologic intervention with somatostatin and insulin (physiologic dose) can facilitate glucose utilization and oxidation in these patients. Further investigations are needed to determine whether long-term alteration of glucose and fat metabolism would be beneficial in the patient with secondary multiple organ dysfunction syndrome. PMID- 8001391 TI - Prediction of outcome in intensive care patients using endocrine parameters. AB - OBJECTIVE: To determine the ability of various endocrine parameters, measured at the time of intensive care unit (ICU) admission, to predict patient outcome. DESIGN: Prospective, cohort study of patients requiring intensive care. SETTING: The medical/surgical ICU at South Cleveland Hospital, UK and a medical/surgical ICU in a UK district hospital. PATIENTS: A total of 260 consecutive patients requiring intensive care over a 2-yr period. INTERVENTIONS: Patients were investigated within 1 hr of ICU admission by measuring plasma cortisol, serum thyroxine, triiodothyronine, and thyrotropin concentrations and by obtaining the Acute Physiology and Chronic Health Evaluation (APACHE II) score. Individual variables were compared between survivors and nonsurvivors. MEASUREMENTS AND MAIN RESULTS: There were significant differences for each endocrine parameter between survivors and nonsurvivors (all p < .01). A multiple logistic regression analysis showed that only thyroxine, thyrotropin, and cortisol concentrations were independent predictors of outcome. An equation using these variables predicted outcome with 82% accuracy at the 0.5 cutoff point of the receiver operating curve. APACHE II scores predicted outcome with 72% accuracy at the same point on the receiver operating curve. Correct prediction of death was more frequent with the Endocrine Index than with APACHE II scores. Overall predictive power of the Endocrine Index, as measured by the area under the receiver operating curve, was 0.94 (95% confidence interval 0.91 to 0.96) vs. 0.85 (95% confidence interval 0.81 to 0.89) for APACHE II scores. Combining APACHE II scores and the endocrine parameters in a single index did not improve prediction (area under receiver operating curve = 0.94). CONCLUSION: An endocrine prognostic index based on ICU admission measurements of thyroxine, thyrotropin, and cortisol concentrations is a superior discriminator of patient outcome than the APACHE II score. PMID- 8001393 TI - Pretreatment of normal humans with monophosphoryl lipid A induces tolerance to endotoxin: a prospective, double-blind, randomized, controlled trial. AB - OBJECTIVES: Endotoxin is one of the principal mediators of Gram-negative septic shock. Pretreatment with monophosphoryl lipid A, a hydrolyzed derivative of endotoxin from Salmonella minnesota R595, induces endotoxin tolerance and nonspecific resistance to infection in experimental animals. The present clinical trial was undertaken to test the response to monophosphoryl lipid A in humans and the ability of monophosphoryl lipid A to attenuate the response of normal human volunteers to U.S. Reference Ec-5 endotoxin. DESIGN: Prospective, double-blind, randomized, controlled trial. SETTING: Clinical research center. PATIENTS: Forty four healthy volunteers. INTERVENTIONS: In part 1 of the study, 29 volunteers were randomized in varying ratios to receive vehicle control or monophosphoryl lipid A intravenously in a double-blind dose escalation trial. In part 2 of the study, 12 volunteers were randomized to receive either monophosphoryl lipid A (20 micrograms/kg) or vehicle control and, 24 hrs later, all 12 volunteers were challenged with U.S. Reference Ec-5 endotoxin (20 units/kg intravenous, bolus injection). Systemic response to endotoxin challenge was evaluated and compared between the monophosphoryl lipid A and vehicle control-pretreated subjects. MEASUREMENTS AND MAIN RESULTS: In part 1 of the study, subjective effects and increases in cytokine levels were not observed until a dose of 10 micrograms/kg of monophosphoryl lipid A was administered. Six volunteers receiving a maximum dose of 20 micrograms/kg experienced mild-to-moderate symptoms that did not require therapy. Moderate increases in temperature, heart rate, and tumor necrosis factor (TNF)-alpha, interleukin (IL)-6, and IL-8 release were observed. IL-1 alpha and IL-1 beta were not detected but a significant increase in IL-1 receptor antagonist was observed. In part 2 of the study, monophosphoryl lipid A pretreatment reduced the number of volunteers who experienced one or more subjective complaints after endotoxin administration (3/6 vs. 6/6; p = .09). The febrile response and tachycardic response to endotoxin were significantly reduced by pretreatment with monophosphoryl lipid A. Monophosphoryl lipid A-pretreated volunteers demonstrated significantly reduced concentrations of TNF-alpha after endotoxin challenge, as compared with subjects treated with vehicle control (84 +/- 76 vs. 244 +/- 128 pg/mL; p < .05). IL-6 concentrations (100 +/- 91 vs. 268 +/- 171 pg/ml; p < .05) and IL-8 concentrations (136 +/- 86 vs. 632 +/- 323 pg/mL; p < .05) elicited by endotoxin challenge were also significantly reduced by monophosphoryl lipid A pretreatment. CONCLUSIONS: Data indicate that monophosphoryl lipid A, in a dose 10,000 times that of endotoxin, used in experimental pyrogenicity trials, is well tolerated in human volunteers. Pretreatment of normal human volunteers with monophosphoryl lipid A attenuated the systemic response to bacterial endotoxin. These data support further clinical testing of monophosphoryl lipid A for the prevention or amelioration of the severe sequelae of sepsis. PMID- 8001394 TI - Recombinant endotoxin neutralizing protein improves survival from Escherichia coli sepsis in rats. AB - OBJECTIVE: A recombinant endotoxin neutralizing protein was evaluated for its ability to ameliorate the effects of Escherichia coli sepsis in rats. DESIGN: Prospective, controlled animal trial. SETTING: Hospital animal research laboratory. SUBJECTS: Wistar rats, treated with gentamicin 1 hr after challenge with intraperitoneal E. coli O18ac. INTERVENTIONS: The animals received a recombinant endotoxin neutralizing protein, in doses of 5, 25, or 50 mg/kg, either 30 or 60 mins after challenge; controls received saline. MEASUREMENTS AND MAIN RESULTS: Geometric mean serum endotoxin concentrations in endotoxin neutralizing protein-treated animals did not differ from control animals. Tumor necrosis factor concentrations in animals treated with endotoxin neutralizing protein 30 mins after challenge were significantly lower than controls. Animals treated with 25 or 50 mg/kg of endotoxin neutralizing protein 30 mins after E. coli challenge had significant improvements in survival compared with controls. Animals treated with 50 mg/kg of endotoxin neutralizing protein 60 mins after E. coli challenge had significant improvements in survival compared with controls. CONCLUSION: Endotoxin neutralizing protein significantly reduces mortality from Gram-negative sepsis in an antibiotic-treatment model of E. coli peritonitis and bacteremia in rats, mediated by a neutralization of the biological effects of endotoxin. PMID- 8001392 TI - Soft tissue infection prophylaxis with gentamicin encapsulated in multivesicular liposomes: results from a prospective, randomized trial. AB - OBJECTIVES: Systemically administered antibiotic agents are not evenly distributed in the body, which frequently results in subtherapeutic regional drug concentrations, particularly in areas of poor vascularization, including wound sites. We have developed a lipid-based drug delivery system to provide prolonged levels of gentamicin in local tissues after local administration. Multivesicular liposomes are microspheres composed of lipid bilayer membranes surrounding multiple aqueous compartments that can contain drug. The preparation may be effective for the prevention and treatment of a variety of infections, including infections associated with indwelling vascular catheters. DESIGN: Prospective, randomized trial. SETTING: Animal laboratory. SUBJECTS: Mice, 6 to 12 wks of age, weighing 20 to 30 g. INTERVENTIONS: We administered 0.5 mg of gentamicin encapsulated in multivesicular liposomes to dorsal subcutaneous tissue in mice. Animals were inoculated with 10(5) to 10(7) colony-forming units (cfu) of Staphylococcus aureus 2, 4, 6, and 8 days later. The cfu/g of tissue values were determined 2 days after inoculation. MEASUREMENTS AND MAIN RESULTS: With a 10(7) cfu challenge, animals that received 2- and 4-day pretreatment with multivesicular liposome/gentamicin had a 4 log10 reduction in cfu/g of tissue compared with controls. When 10(5) cfu of Staphylococcus aureus were inoculated after 2- and 4-day pretreatment with multivesicular liposome/gentamicin, a 6 log10 reduction in bacteria colony-forming units was observed. CONCLUSION: Local injection of multivesicular liposome/gentamicin provides sustained drug concentrations in regional tissues that protect against a massive bacterial challenge for at least four subsequent days. PMID- 8001395 TI - Removal of platelet-activating factor in experimental continuous arteriovenous hemofiltration. AB - OBJECTIVE: There is a positive correlation between the amount of ultrafiltration and the improved survival rate of patients with ischemia or sepsis-induced acute renal failure. Continuous arteriovenous hemofiltration (CAVH) removes vasoactive substances with a molecular weight of < 1000 daltons. This study evaluated the removal of platelet-activating factor, a lipid mediator of endotoxic shock, by CAVH with respect to kinetics, adsorption, and ultrafiltration. DESIGN: Prospective laboratory study. SUBJECTS: Normal human subjects. INTERVENTIONS: Radioactive [3H] or biologically active platelet-activating factor was added to whole blood or washed blood resuspended in Tris-buffered (pH 7.2) physiologic saline with 4% human serum albumin or plasma. Whole or washed blood cells or plasma were recirculated at 100 mL/min through polysulfone hemofilters for 120 mins with ultrafiltration (condition A), without ultrafiltration (condition B), or in a static condition (condition C). Concentrations of albumin, total protein, and radioactive or biologically active platelet-activating factor in samples obtained from the blood and ultrafiltrate compartment were determined. MEASUREMENTS: Biologically active platelet-activating factor was quantified on washed rabbit platelets and results were expressed in ng/mL over a calibration curve obtained with synthetic platelet-activating factor. MAIN RESULTS: [3H] platelet-activating factor added to recirculated whole blood was ultrafiltered (percent of ultrafiltered platelet-activating factor/min: 0.48 +/- 0.02 [SD]; total platelet-activating factor removed in 120 mins: 15.52%; condition A) at significantly (p < .001) higher amounts than when added to washed blood cells (percent of ultrafiltered platelet-activating factor removed/min: 0.195 +/- 0.06; total platelet-activating factor removed in 120 mins: 7.46%). The highest amounts of [3H]-platelet-activating factor were bound to polysulfone membranes after recirculation with whole blood (44.5 +/- 12.2%) than with washed blood (1.1 +/- 0.3%) or plasma (11.9 +/- 0.7%). Biologically active platelet-activating factor concentrations significantly decreased in both conditions A and B (maximal decrease at 120 mins: 63% and 59%, respectively). No significant reduction could be observed in condition C. CONCLUSIONS: These studies provide experimental evidence for the prompt, efficient removal of platelet-activating factor in CAVH and provide a possible rationale for the beneficial effect of this therapy in the development of multiple organ failure in sepsis. PMID- 8001396 TI - Role of ryanodine receptors. AB - Recent findings on the ryanodine receptor of vertebrates, a Ca-release channel protein for the caffeine- and ryanodine-sensitive Ca pools, are reviewed in this article. Three distinct genes, i.e., ryr1, ryr2, and ryr3, express different isoforms in specific locations: Ryr1 in skeletal muscle and Purkinje cells of cerebellum; Ryr2 in cardiac muscle and brain, especially cerebellum; Ryr3 in skeletal muscle of nonmammalian vertebrates, the corpus striatum, and limbic cortex of brain, smooth muscles, and the other cells in vertebrates. While only one isoform (Ryr1) is expressed in mammalian skeletal muscles, two isoforms (alpha- and beta-isoforms expressed by ryr1 and ryr3, respectively) are found in nonmammalian vertebrate skeletal muscles. Although the coexistence of two isoforms may merely be related to differentiation and specialization, the biological significance remains to be clarified. Ryanodine receptors in vertebrate skeletal muscles are believed to mediate two different modes of Ca release: Ca(2+)-induced Ca release and action potential-induced Ca release. All results obtained so far with any isoform of ryanodine receptor are related to Ca(2+)-induced Ca release and show very similar characteristics. Ca(2+)-induced Ca release, however, cannot be the underlying mechanism of Ca release on skeletal muscle activation. Susceptibility of the ryanodine receptor's ryanodine-binding activity to modification by physical factors, such as osmolality of the medium, might be related to action potential-induced Ca release. A hypothesis of molecular interaction in view of the plunger model of action potential-induced Ca release is discussed, suggesting that the model could be compatible with Ryr1 and Ryr3, but incompatible with Ryr2. The functional relevance of ryanodine receptor isoforms, especially Ryr3, in brain also remains to be clarified. Among ryr1 gene related diseases, malignant hyperthermia was the first to be identified; however, there is still the possibility of involvement of the other genes. Central core disease has been added to the list recently. A molecular approach for the diagnosis and treatment of diseases is now in progress. PMID- 8001397 TI - Phase separation of biomolecules in polyoxyethylene glycol nonionic detergents. AB - The advantage of aqueous two-phase systems based on polyoxyethylene detergents over other liquid-liquid two-phase systems lies in their capacity to fractionate membrane proteins simply by heating the solution over a biocompatible range of temperatures (20 to 37 degrees C). This permits the peripheral membrane proteins to be effectively separated from the integral membrane proteins, which remain in the detergent-rich phase due to the interaction of their hydrophobic domains with detergent micelles. Since the first reports of this special characteristic of polyoxyethylene glycol detergents in 1981, numerous reports have consolidated this procedure as a fundamental technique in membrane biochemistry and molecular biology. As examples of their use in these two fields, this review summarizes the studies carried out on the topology, diversity, and anomalous behavior of transmembrane proteins on the distribution of glycosyl-phosphatidylinositol anchored membrane proteins, and on a mechanism to describe the pH-induced translocation of viruses, bacterial endotoxins, and soluble cytoplasmic proteins related to membrane fusion. In addition, the phase separation capacity of these polyoxyethylene glycol detergents has been used to develop quick fractionation methods with high recoveries, on both a micro- and macroscale, and to speed up or increase the efficiency of bioanalytical assays. PMID- 8001399 TI - Meiosis and chromosomal effects of thio-TEPA in the ovarian cells of Aedes aegypti. AB - The development of meiosis during oogenesis in the normal, and 0.1% thio-TEPA (triethylene thiophosphoramide) fed female of Aedes aegypti was studied. Chromosome preparations were made from adults 24 h after a blood meal. The frequency of various kinds of chromosomal abnormalities was analysed. PMID- 8001400 TI - Dual modulation of the phosphorylation of endogenous yeast proteins by arachidonic acid and phosphatidylinositol. AB - Phosphorylation of endogenous yeast substrates in DE-52 fractions were analysed by SDS-polyacrylamide gel electrophoresis and autoradiography. In fractions 29 and 45, phosphatidylinositol inhibited the phosphorylation of multiple peptides with a wide range of molecular mass whereas it enhanced the phosphorylation of peptides smaller than 14 kD. Similar dual modulation of the phosphorylation by arachidonic acid was observed in fraction 37 which also contained potent phosphatidylserine-activating protein kinase C. PMID- 8001398 TI - Further cytogenetic variations in the karyotype of Erinaceus europaeus (Insectivora, Mammalia). AB - Cytogenetic studies of Erinaceus europaeus from a Spanish population, including C banding, simultaneous Ag-staining of nucleolus organizer regions (NORs) and G banding, and chromomycin A3 staining, are described. With regard to the number and morphology of chromosomes, Spanish hedgehogs showed a karyotype very similar to that described by Mandal for Northern Europe specimens, referred to as the WII karyotype. Clear differences were observed in the presence or absence of centromeric C-bands and the number and position of NORs. A new karyotypic form, provisionally designated the S (south) karyotype, is proposed. PMID- 8001401 TI - In situ nick translation of human chromosomes with the restriction endonuclease Pvu II [5' CAG decreases CTG 3']. AB - The treatment of fixed human chromosomes by a number of restriction endonucleases has opened additional avenues towards understanding the mechanism(s) of chromosome banding. Metaphase chromosomes from five unrelated individuals were treated with restriction endonuclease Pvu II [CAG decreases CTG] which has a 6 bp recognition site. The banding patterns were compared with another restriction endonuclease Alu I [AG decreases CT] which recognizes only 4 bp but the recognition sequences are identical. The results demonstrate that the banding pattern of human chromosomes observed by Pvu II digestion are apparently identical to those observed by Alu I. The mechanisms of chromosomal banding are discussed. PMID- 8001402 TI - [Evaluation of fetal well-being by vibro-acoustic stimulation test]. AB - For monitoring of fetal well-being, non-stress test (NST) and vibro-acoustic stimulation test (VAS-T) were tested simultaneously in 295 normal pregnant women with gestational age over 36 weeks. In 130 women who delivered babies within 1 week after testing, the monitoring results were compared with the newborn's condition immediately after birth. The results showed that VAS-T improved the accuracy rate diagnosed by NST and shorten the time period required for examination. The clinical significance of 5 different wave forms of VAS-T were studied. Type I and Ib were typical reactive pattern which represented a good fetal condition. Type II, III and IV suggested that the fetus were in various degree of hypoxia. Specifically, Type III reflected the cord around the neck, and type IV was a sign of severe fetal distress and nervous system defect. PMID- 8001403 TI - [Puerperal infection of ureaplasma urealyticum]. AB - Using indirect agglutination test (IAT), ELISA and metabolic inhibition test (MI), serum specific IgM antibodies to ureaplasma urealyticum (Un) was investigated in 160 women of late pregnancy during the period of 1991-1992. 81 cases (50.6%) were found positive. 65 out of 81 positive mothers had umbilical blood samples examined and placenta tissues cultured. Specific IgM was detected in the umbilical blood of 7 women (10.8%), and ureaplasma urealyticum was isolated from 6 placenta (9.2%). Among Un IgM positive women, 28 (34.6%) were complicated with puerperal fever, and 30 newborns suffered from neonatal pneumonia and fever, which were significantly higher than that in the Un IgM negative group (P < 0.05). This study indicated that ureaplasma urealyticum might be one of the important pathogens for puerperal and neonatal infection. PMID- 8001404 TI - [Application of nitrous oxide in labor analgesia]. AB - Labor analgesia with nitrous oxide was studied in 34 parturients, and another 50 women taking no drug as the control group. The analgesic effect was satisfactory. By Mulleetr's pain in labor score, 91.18% women had score of 0-1, and their respiratory and circulatory functions were not affected. During inhalational analgesia the parturients remained conscious. Uterine contraction, progress of labor and neonatal Apgar score were not interferred, and postpartum bleeding was not increased. There was no complications in the treatment group. This study suggests that nitrous oxide with enough oxygen inhalation is one of the good drug for obstetric analgesia, but its concentration must be strictly controlled. PMID- 8001405 TI - [The rapid activation of human LAK cells and their inhibition on ovarian cancer at the advanced stage]. AB - The study of generation of LAK cells from cord blood following a brief exposure to interleukin-2 (IL-2) demonstrated that a short time induction (15min-1h) of lymphocytes by a high concentration of IL-2 resulted in the maturation of LAK proceusor cells and such activated cells expressed cytolytic activity comparable to that of routinely induced (cultured continuously in IL-2 for 3-7 days) lymphocytes. Serologic test showed that this efficiency was not inhibited by autoserum. The results of experimental therapy with the two kinds of LAK cells in nude mouse model of human ovarian cancer confirmed that both types of LAK cells had remarkable inhibitory effect on tumor growth. The preliminary trial in the treatment of advanced ovarian cancer with rapid-pulsed LAK cells suggested that this method may serve as a new approach in the clinical application of tumor immunotherapy. PMID- 8001406 TI - [The diagnostic value of the assay of lactate dehydrogenese combined with other tumor markers in ovarian cancer]. AB - Thirty-five cases of ovarian cancer, 35 ovarian benign tumors, 31 other gynecologic cancer and 35 normal controls were assayed for LDH, LDH-isoenzyme, SA, CEA, beta 2-MG and AKP. The results showed: (1) The average content of tumor markers in ovarian cancer was higher than benign tumor and healthy controls. (2) The positive rate of tumor markers in stage I and II patients of ovarian cancer was lower than in stage III and IV. (3) In the tumor markers, the diagnostic value of LDH-isoenzyme for ovarian cancer was best. (4) Combined assaying LDH, LDH-isoenzyme and SA was superior to using one marker for the diagnosis of ovarian cancer. PMID- 8001407 TI - [Radioimmunoimaging assay of ovarian tumor with 99mTc labeled anti carcinoembryonic antigen monoclonal antibody]. AB - Radioimmunoimaging (RI I) assay with 99mTc labeled anti-CEA monoclonal antibody was performed in 31 patients with suspected primary or recurrent malignant ovarian tumor. The radiation dose raging from 920MBq to 110MBq(1mgIgG) was administered i.v. for each patient. Anterior-posterior views of the pelvis and abdomen were obtained routinely with gamma-camera during 18-24 hour after the application of antibody. The results of RII were compared with the findings in operation or CT examination. Sensitivity in diagnosis was 100% (13/13), specificity was 94%(16/17) and metastatic foci sensitivity was 63%(10/16). The serum CA125 in this study appeared to be correlated with the results of RII. However, in 2 patients with normal serum CA125 titers RII revealed true positive. The preliminary clinical results of RII with 99mTc-MAb showed that RII is a promising method for the detection of malignant ovarian tumors. PMID- 8001408 TI - [The detection of human papillomavirus DNA in normal cervical tissue by polymerase chain reaction technique]. AB - The consensus and complex human papillomavirus-polymerase chain reaction (HPV PCR) technique was used to detect HPV-DNA in normal cervical tissue of 148 women. The investigation showed that HPV-DNA positive rate was 31.76% (47/148) including HPV type 6,11, 6.76% (10/148), HPV type 16, 18, 3.38% (5/148) and other types 21.62% (32/148). HPV infection was more common in young women from 22 to 34 years of age. The transmission route of female genital HPV infection and the importance of subclinical infection were also discussed. PMID- 8001409 TI - [The effects of the estradiol control delivery patch in the treatment of 176 cases of ovarian failure]. AB - The effects of the estradiol control delivery patch made in China on the main manifestation in the 176 cases of ovarian failure patient were evaluated with the improvement of their symptoms, the changes of serum levels of LH, FSH, E2, the vaginal exfoliated cytologic maturation index (MI) and the histological alteration of endometrium. The results indicated that the six main symptoms including hectic fever, sweating, vaginal dry and hard-going, dizziness, emotioned lability and insomnia were improved significantly and progressively with prolongation of the treatment. The effective rates were 97.9%, 97.5%, 93.7%, 77.0%, 76.2%, 75.0% respectively form hectic fever to insomnia. The inhibitory effects on serum LH, FSH levels occurred on the 10th day of the treatment. The MI increased within whole course and the serum estradiol level elevated slightly and stably. There were no significant endometrial proliferation caused by the patch. PMID- 8001410 TI - [The effects of the cyclopentyl ethinyl estriol on the cardiovascular function of postmenopausal women]. AB - The cardiovascular function of postmenopausal women before and after oral supplement of cyclopentyl ethinyl estriol (CEE3) were evaluated with 3 dimensional ultrasound and Doppler technique. The results are as follows: there were no changes of HR, SBP, DBP, MBP and E2 in postmenopausal women before and after the oral supplement of CEE3. Ves and SVR were obviously reduced (P < 0.001). SV, CO, EF, Vmax V and A were obviously increased (P < 0.001). There were no changes in Ved, E and E/A. The results showed that CEE3 could reinforce the cardiac function and increase cardiac output and also reduce the resistance in peripheral blood vessels in postmenopausal women. It is assumed that the cardioprotective effect of hormone replacement therapy in postmenopausal women may be due not only to changes in lipid profile but also to direct effects of estrogens on central and peripheral hemodynamic parameters. PMID- 8001411 TI - [The prospect of biologic therapy in ovarian cancer]. PMID- 8001412 TI - [Tumor necrosis factor gene expression in ovarian tumor]. AB - The tumor necrosis factor (TNF) gene expression in ovarian tumor was observed with digoxigenin labeled TNF-alpha cDNA probes and in situ hybridization technique. 54 cases of fresh biopsies of the ovarian tumor and 10 cases of normal ovaries were snap frozen sectioned. The results showed that the average positive rate of TNF gene expression in some ovarian cells and tumor infiltrating lymphocytes (TIL) was higher than that in the borderline and benign tumor cells and TIL. The more advanced clinical stages, the higher does positive rate of TNF gene expression in the cancer cell and the smaller dose in the TIL. It was appeared that TNF gene expression of the tumor cells and TIL was connected with clinical stage and tissue typing of ovarian tumor. The data suggested TNF gene expression of cancer cell might play a role in the progress of ovarian cancer and as a marker of the advanced malignancy tumors. In addition, TNF gene expression of the TIL might mark the restinced state of the host immunology. PMID- 8001413 TI - [Immunologic suppressor factors in sera of patients with ovarian cancer]. AB - The suppressive activity of immunologic suppressor factors (ISF) in the sera of 34 patients with ovarian cancer was investigated by using the lymphocyte proliferation and inhibition test. It was found that the sera of the preoperative patients could significantly suppress PHA-induced lymphocyte response, and that the suppression was dose-dependent. When the sera were diluted to 1 : 4,000, the suppressive activity could still be demonstrated. We also observed the suppressive activities in the sera of patients with cervical cancer, endometrial cancer, gastric cancer and lung cancer, and compared them with ovarian cancer patients. The observation showed that the suppressive activity in the sera of preoperative ovarian cancer patients was higher than that in the sera of gastric cancer or lung cancer patients. These results suggested that ISF played an important role in the development of ovarian cancer. PMID- 8001414 TI - [Production and identification of a monoclonal antibody against a tumor associated antigen from ovarian epithelial carcinoma]. AB - The splenocyte of BALB/c mice, immunized with soluble and ovarian serous papillary cystedenoma-associated antigen CA925, was fused with NS-1 myeloma cell strain to produce a monoclonal antibody. 5 cell strains of the monoclonal antibody with continuous secretion were obtained. The fusion openings were used as code names: OC4D9, OC7E10, OC1B4, OC3B8, and OC9B9, their titers were 1: 10(7), 1: 10(7), 1: 10(6), 1: 10(4) and 1: 10(5) respectively. Ig subgroups were IgM and IgG. The chromosomes showed the characteristics of their parents. The 5 strains of the monoclonal antibody obtained presented specific reactions to CA925, no positive reaction with normal ovarian tissues or leiomyoma of the uterus were seen, and there were weak reactions with carcinomas of the lung, the stomach, the kidney, the esophagus and the rectum. Immunohistochemical tests proved that the monoclonal antibody produced was specific against ovarian epithelial carcinoma, and it might offer a means to the diagnosis and treatment of malignant ovarian tumors. PMID- 8001416 TI - [The antimetastatic effects of BJA-II on nude mice with highly metastatic human ovarian carcinoma]. AB - Nude mice with highly metastatic human ovarian carcinoma were treated with BJA II. This new agent was made in our institute. Twenty-four experimental mice were divided into 4 groups with 6 mice each. The mice, according to the treatment given them, were designated as: the BJA-II group, the cisplatin group, the group with combination therapy and the control group. Treatment began on the 2nd day after tumor transplantation. For BJA-II, a dose of 16 mg per mouse per day was administered orally. The total dose each mouse received by the 53rd day was 848mg. The tumor growth inhibition rate was found to be 63.7% in the BJA-II group; the transplanted tumors disappeared in 2 mice. No significant difference in average tumor weight was found between the BJA-II group and the control group (P < 0.05). The antimetastatic effect of BJA-II (1 mouse with metastasis) was higher than that of the control group (4 mice with metastasis). The influences on the immunofunction of the host were observed: the increase of the peripheral WBC count, the increase of NK cell activity, the increase in the ratio of spleen weight to body weight, and the histiocyte increase in the lymph node sinuses, etc. All of these findings were better demonstrated in the BJA-II group than in the cisplatin group. The results indicate that BJA-II is provided with the effectiveness of inhibiting tumor growth, is antimetastatic and is capable of increasing the immunofunction of the host. PMID- 8001415 TI - [Amplification of C-erB2 gene in ovarian cancer]. AB - In the present report, amplification of C-erbB2 proto-oncogene in ovarian cancer was studied with Southern Blot technique. There were 14 cases to occur amplification of C-erbB2 oncogene in 50 cases with ovarian cancer. Among 14 ovarian cancer cases with amplification of C-erbB2, 2 of 20 cases were detected in stage I and II respectively, while 12 of 30 cases were from stage III/IV (P < 0.05). These results showed that amplification of C-erbB2 proto-oncogene is associated with advanced ovarian cancer. Therefore, it is suggested that C-erbB2 gene amplification may deserve further evaluation as a prognostic marker in ovarian cancer. PMID- 8001417 TI - [Prenatal diagnosis of Duchenne's muscular dystrophy fetus at risk]. AB - Prenatal diagnosis of Duchenne's muscular dystrophy (DMD) have been carried out on 12 fetus at risk. The gene mutations have been identified by hybridization with cDNA probes and/or multiplex PCR. The fetus examined were 7 males and 3 females. Three of the male fetus inherited the same deleted mutations as the probands, and other 4 appeared normal. Among the 3 female fetus, one carried a deleted gene, two were considered normal. The diagnosis of the fetus were confirmed after birth or abortion. As the multiplex PCR can quickly detect about 98% of the deletions on the dystrophin gene, it is not only an idea method for screening the gene deletion but can also be applied to prenatal diagnosis immediately after the nature of the deletion have been identified among the probands. The strategy of prenatal diagnosis of DMD in our country was also discussed. PMID- 8001418 TI - [Variations in ATPase activities of erythrocytic membrane and endocytic ionic levels in cases with pregnancy induced hypertension]. AB - The ATPase activities of erythrocytic membrane and endocytic ionic concentration were determined in 30 cases with pregnancy induced hypertension (PIH), 25 normal pregnancies and 20 non-pregnant controls. The activities of Na(+)-K(+)-ATPase and Ca(++)-ATPase were found significantly lower in PIH than those in the controls, but Mg(++)-ATPase activity revealed no Na+ and Ca++ values were significantly higher while Mg++ obviously lower in those with PIH than in the controls, and K+ was almost the same in the three groups. These findings suggested a close relationship between the pathogenesis of PIH and the abnormal ATPase activities and ionic levels. PMID- 8001419 TI - [Correlation between outcome of pregnancy and condition of disease at conception in systemic lupus erythematosus women]. AB - Thirty four pregnant patients with systemic lupus erythematosus (SLE) were divided into 3 groups: (1) primigravida, (2) previous history of spontaneous abortion, and (3) previous history of induced abortion. Outcomes of these pregnancies showed that the average birth weight in primigravida group was significantly higher than that in the other 2 groups (P < 0.05). Grouping by clinical status of SLE at conception, there were 4 kinds of situation: (1) remission, (2) controlled, (3) active, and (4) first onset. Patients with SLE of active stage had the lowest birth weight and gestational age babies (P < 0.05). The best time for conception in SLE women was at the time of remission or controlled stage, i.e. patients treated with prednisone in a dose of 5-15 mg/day for more than 6 months or without any medication for at least 1 year. PMID- 8001420 TI - [Biological effects of diagnostic ultrasound on embryo in first trimester of pregnancy]. AB - Biological effects of diagnostic ultrasound on the embryo during first trimester of pregnancy were studied. Normal pregnant women asked for induced abortion with gestational age of 6-8 weeks were recruited. Embryo in uterus were exposed to the diagnostic ultrasound for 5, 10 and 30 minutes respectively. Surgical evacuations were performed 5, 15, 24 and 48 hours after exposure and chorionic villi were obtained. The villi were determined for 4 lysosomal enzymes, malondialdehyde (MDA), and superoxide dismutase (SOD); and sister chromatid exchange and the ultrastructure of the villi were studied as well. In comparison to normal non exposure group, the results showed various degrees of changes in lysosomal enzymes, MDA, SOD and ultrastructure of the villi in those exposed to ultrasound 10 and 30 minutes, and most significant changes were observed in the latter group. These included the hyperreaction of lipid peroxides; increased activities of some lysosomal enzymes; reduced SOD activity; and vesiculation and aberration of some mitochondrion, also transformation or disappearance of some microvilli in ultrastructure. PMID- 8001421 TI - [Glycosylated hemoglobin assay and its research progress in obstetrics]. PMID- 8001422 TI - [Application of polymerase chain reaction techniques to obstetrics and gynecology]. PMID- 8001423 TI - [The dynamic changes of serum antibody levels in adult periodontitis patients before and after extraction of teeth]. PMID- 8001424 TI - [A preliminary study of testing pulp vitality by the dental phosphorescent detective instrument]. PMID- 8001426 TI - [Computer-aided videos system for evaluation of occlusal contacts]. PMID- 8001425 TI - [Immunohistochemical studies of Langerhans cells and keratinocytes and T cell subsets in oral lichen planus by anti-T6, anti-HLA-DR, and anti-T3, T4, T8]. PMID- 8001427 TI - [Advanced tooth wear and restoration]. PMID- 8001428 TI - [The preliminary observation of orthodontic treatment of cleft lip and palate infant patients]. PMID- 8001429 TI - [Clinical manifestations, diagnosis and treatment of thyroid cancer in oral and maxillofacial surgery]. AB - The authors summarized the experiences of management for 15 patients with thyroid cancer from 1964 to 1992. Nine patients were incorrectly diagnosed. Among them, 7 patients actually had one or several dominant masses of thyroid gland, unfortunately, these masses had not been found by doctors who ignored to examine thyroid gland before these patients were performed the first operation. All patients had been operated and follow-up postoperatively. This paper mainly discussed the reason of incorrect diagnosis, method of therapy and result of treatment for 15 patients suffering from thyroid cancer in our department. PMID- 8001430 TI - [Relationship of serum and gingival crevicular fluid antibody levels with the amount of subgingival homologous bacterium in patients with periodontal disease]. AB - 39 patients were selected in this study, including 12 patients with rapidly progressive periodontitis (RPP), 17 with adult periodontitis (AP) and 10 with marginal gingivitis (MG). The levels of antibody to Porphyromonas gingivalis (Pg) in serum (Sr) and in gingival crevicular fluid (GCF) from their 156 teeth were measured by ELISA. The Pg in subgingival plaque was detected by indirect immunofluorescence technique. Data showed different GCF/Sr ratio of anti--Pg antibody level between periodontitis patients (lower than 1) and MG patients (greater than 1). The amount of subgingival Pg was negatively correlated with clinical periodontal parameters, i.e, probing depth, attachment loss, plaque index and bleeding index. It was suggested that low GCF/Sr ratio of antibody level plus high counts of homologous bacterium might be used as an indicator of periodontal disease activity. PMID- 8001431 TI - [Effects of permanent magnetic field on DNA metabolism of human periodontal ligament fibroblasts in vitro]. AB - In order to investigate the biological effects of permanent magnetic field on cell's DNA metabolism, human periodontal ligament (PDL) fibroblasts in vitro were treated in a DC electromagnetic field with strength of 0.14T. The microscopic spectrum quantitative analysis showed that in once-everyday-treating group, the DNA contents in cells increased if they were treated 10, 40, 60 and 120 minutes everyday in one week and the longer the treating time lasted, the more remarkably the DNA contents increased. But in the other two groups, in which cells were treated once every other day as well as one time in one week, no remarkable changes were found. It indicated that 0.14T magnetic field has a time-delayed effect and an accumulation effect on PDL cell's DNA metabolism. When the threshold was achieved, it could promote the cell's DNA synthesis. PMID- 8001432 TI - [Experimental study on the role of oxygen-free radicals in ischemic reperfusion tissue injury is island skin flaps]. AB - In this study the role of oxygen-free radicals and the effect of treatment with superoxide dismutase (SOD) had been investigated in a 3 x 6 cm2 abdominal area island skin flaps of rat model which were subjected to 8 hours of total venous occlusion. In experiment 1, 56 rats were divided into seven test groups. Tissue assay for Malonydialdehyde (MDA) were obtained. Flaps with ischemia had higher MDA at 8.12 hours and all reperfusion groups had higher MDA as compared to the control groups (P < 0.01). In reperfusion groups, the MDA had increased at 4.8 hours compared to ischemia group at the same time. In experimental 2, 28 rats were used. Treatment with superoxide dismutase injected into the artery following the onset of reperfusion significantly enhanced island flap survival from 28.6% (4/14) to 78.6% (11/14) (P < 0.01). PMID- 8001433 TI - [An immunoelectron microscopic study of the myoepithelial cells in salivary gland pleomorphic adenoma]. AB - In the present study, the neoplastic myoepithelial cells in five pleomorphic adenomas of parotid gland were labeled with actin, myosin, S-100 protein, glial fibrillary acidic protein (GFAP) and vimentin. We have found that the neoplastic myoepithelial cells have many different morphologic features, they are the principal proliferating cells in the tumors. In the myxoid region, part of the neoplastic myoepithelial cells have early chondroid differentiation, this shows that the neoplastic myoepithelial cells take the important role in the histogenesis of the tumors. PMID- 8001434 TI - [The study on the relationship between the malocclusion of the third molar and craniomandibular dysfunction]. AB - A total of 33 craniomandibular dysfunction (CMD) patients with third molar malocclusion were studied for their occlusion, condyle position, the TMJ arthrograph and EMG of upper and lower lateral pterygoid muscle (Lpt). The results showed that the condyle displacement was related to the malocclusion of third molar, of which it may induce TMJ click as the result of loss of disccondyle harmonious relationship. Most of the patients showed the abnormal EMG of Lpt. Among which some click TMJ showed no obvious condyle displacement while on the others felt severe pain without TMJ click. It can be considered that both the malocclusion of third molar and dysfunction of Lpt may be the cause of TMJ click. PMID- 8001435 TI - [Vascular anomalies of the maxillofacial region]. AB - 513 cases with vascular lesions of oral and maxillofacial regions were followed from 1986 to 1990 by history, physical examination and pathological check. The vascular anomalies which had been termed "hemangioma" in the past were diagnosed anew according to new biological classification of vascular lesions proposed by Mulliken and Glowacki. Hemangioma and vascular malformation were completely different in clinical behavior and endothelial cell characteristics. Hemangiomas are often not present at birth, but appear during the 1st month. Its clinical behavior is that a proliferative phase is followed by a slow involution. Vascular Malformations are always present at birth and never regress, therefore the treatment of hemangioma and vascular malformation is different. PMID- 8001436 TI - [A study of computed tomography of elderly temporomandibular joint disorders syndrome (TMJDS) patients treated with and without splint in three dimensions]. AB - The computed tomography of elderly TMJDS patients treated with and without splint were studied in three dimensions. The results showed that the condyle was in a retruded position in the glenoid fossa in sagittal dimension and the horizontal condylar angle appeared asymmetry in axial dimension. Under the splint treatment, the retruded condyle can be adjusted to the center of the glenoid fossa and the horizontal condylar angle can be balanced, since the splint may correct the vertical dimension and eliminate the occlusal interferences. This study indicates that the horizontal condylar angle can be considered as a significant factor in diagnosis of TMJDS and evaluation of the outcome of treatment. PMID- 8001437 TI - [Surgical anatomy of the extracranial section of the facial nerve in the infant]. PMID- 8001438 TI - [Anti-fracture strength and fracturing work of experimentally incomplete fractured teeth filled with amalgam or composite resin in vitro]. PMID- 8001439 TI - [Comparison of 0.1% dipivalyl epinephrine and 1% epinephrine in patients with glaucoma or ocular hypertension]. AB - The effect of 0.1% dipivalyl epinephrine on intraocular pressure was compared with 1% epinephrine in patients with primary open-angle glaucoma or ocular hypertension. In this study, the two drugs significantly lowered intraocular pressure, with no significant differences being observed. In dipivalyl epinephrine group, no significant ocular or systemic adverse reactions, including heart rate and blood pressure, were observed except mild dilation of pupil. PMID- 8001440 TI - [A randomized controlled study of the anti-cicatricial effect of preoperative subconjunctival triamcinolone on the filtering bleb]. AB - A randomized controlled study of the anticicatricial effect of preoperative subconjunctival triamcinolone acetonide (TA) on the filtering bleb in 89 eyes (61 cases) of refractory glaucoma showed that the rates of surgical success in the TA groups were 77.3-89.0% and that in the control group 48.0%. The varying dosages of TA produced insignificant differences; however, the proportional distribution of the types of filtering blebs differed significantly among the various dosage groups, and complications occurred mostly in the high dosage group of 12 mg. The study indicated that TA raised the surgical efficacy in treating refractory glaucoma and the dosages of choice were 4-8mg. PMID- 8001441 TI - [1,017 cases of posterior chamber IOL implantation]. AB - Based on 1,017 consecutive cases (1,119 eyes) of modern extracapsular extraction with posterior chamber IOL implantation, the authors report their experience in the management of 11 complications, such as turbid posterior capsule, iris synechiae, pupil capture, etc. The period of follow-up ranged from 2 to 68 months, averaging 18.4 months. Disregarding 76 eyes of low vision due to preoperative fundus diseases, 981 (94.1%) of the 1,043 eyes operated achieved corrected vision of 0.5 or better. PMID- 8001443 TI - [Intraocular lens implantation in Fuchs' syndrome]. AB - 10 patients of Fuchs' syndrome underwent ECCE with IOL implantation. The etiopathology of this disease, the prevention and management of intra- and post operative complications were discussed. Three months after the operation, the rate of corneal endothelial cell loss was 23.96%. After an average follow-up of 20 months, 80% of the cases obtained corrected visual acuity of 0.5 and over, indicating that the procedure had been rewarding and safe. PMID- 8001442 TI - [A report of 412 consecutive posterior chamber intraocular lens implantations]. AB - The series of 412 consecutive PC IOL implantations comprised 337 eyes of senile cataract, 16 eyes of membranous cataract, 25 eyes of traumatic cataract, 13 eyes of congenital cataract, 10 eyes of complicated cataract and 11 eyes of aphakia. 362 eyes were postoperatively followed up from 4 weeks to 1 1/2 years with the results that 251 (69.3%) eyes obtained visual acuities of 0.8 or over, and 328 (90.6%) eyes 0.5 or over. The authors discussed the technical improvement in anterior capsulotomy and the implantation procedures in cases of posterior capsule rupture. The importance of postoperative control and management of astigmatism, in the recovery of visual acuity was pointed out. PMID- 8001444 TI - [Triamcinolone acetonide in the prevention of experimental proliferative vitreoretinopathy]. AB - Macrophages were used to induce an experimental model of proliferative vitreoretinopathy (PVR) for the evaluation of drug efficacy of triamcinolone acetonide in the prevention of PVR. After injection of macrophages into the rabbit vitreous, 1 mg of triamcinolone and 0.1 ml saline, respectively, were also injected into the vitreous of the treated group and the control group. Afterwards, on the 28th day, retinal detachment developed in 77% of the eyes in the control group and in 13% of the eyes in the treated group (n = 30, P < 0.01). The time of triamcinolone being cleared up from the vitreous was 35-63 days (average 45.5 days). Electroretinogram and transmission electron microscopic examinations demonstrated that up to 4 mg of triamcinolone was nontoxic to the retina. The results suggest that during inflammatory stage, the use of triamcinolone effectively and safely prevent the development of PVR. PMID- 8001445 TI - [Photogenic retinal damage and its medicinal prevention: lipid peroxide studies]. AB - Continuous illumination of 18,175 lx caused degeneration of the retinal photoreceptor cells in albino rats, accompanied by increase of malondialdehyde (MDA) 3 days after the light exposure. The MDA decreased gradually to return to normal 8 days after the exposure. Administration of vitamin E or beta-carotine both prevented the increase of retinal lipid peroxide with amelioration of the photic injury to the retinal structures, though the effects were closely related to the dosage and time of medication. PMID- 8001446 TI - [A pharmacokinetic study of subconjunctival polyphase liposome 5-fluorouracil]. AB - 5-Fu polyphase liposome was prepared by fusing the drug with lecithin and cholesterol, the rate of encapsulation being 52%, and 97% of the particles were less than 2 microns in diameter and stable against heat and cold. 5 mg of tritiated 5-Fu in 0.5 ml of the polyphase liposome preparation was injected subconjunctivally in rabbits. The concentrations of 5-Fu in the conjunctiva, the sclera, and the conjunctiva-Tenen's capsule-sclera en bloc 180 degrees from the site of injection were measured by the scintillation method 12, 24, 48, 72 and 96 hours after injection to be no less than 0.2 microgram, the ID50 of fibroblast proliferation. These findings suggested that 5-Fu polyphase liposome preparation might be substituted for 5-Fu solution in the filtering operation to reduce the frequency of injections and to attenuate the side effects. PMID- 8001447 TI - [Cephradine delivery into the eye with domestic collagen shield]. AB - The author reports that enhancement by the native made collagen-shield on the permeation of cephradine into the eye is 1.5 times and 1.3 times versus controls when the corneal epithelium is intact or defect, and is 10 times versus frequent eyedrops instillation. On the other hand, the enhancement of the collagen-shield is about the same as that of the soft contact lens impregnated with cephradine solution, but the drug concentration in aqueous humor is increased by collagen shield 1-2 times than that by the wet soft contact lens. These results indicate that the collagen-shield can effectively increase the drug concentration in aqueous humor. PMID- 8001448 TI - [Establishment of a primary eye care network and creation of a cataract-free zone in Shunyi County of Beijing]. AB - Based on the epidemiological survey of eye diseases in 1985, a primary eye care network was established in Shunyi County of Beijing in 1987. Cataract surgery was the primary measure for the prevention of blindness, with the aim of creating a cataract-free zone in the county. The activities included (1) establishment of a County Guiding Committee for the prevention of blindness; (2) establishment of a 3-levelled primary eye care network and a referral and monitor system; (3) training of 7 ophthalmologists, 449 eye care workers and 6 optometrists; (4) extensive publicity of knowledge for the prevention of blindness; (5) screening of low vision and blindness in which 815 cataract blind patients were identified; and (6) conducting benefit ophthalmic counselling services. Up to December, 1991, 667 cataract operations were performed, representing 81.84% of the total cataract blind, to meet the qualifications of a cataract-free zone. 90.64% of the blind were restored sight and 59.16% of the blind were able to resume work. Operative infection occurred in none and 97.42% of the operations had no complication. PMID- 8001449 TI - [Development of a new fundus image processing system for diagnosis of glaucoma]. AB - For diagnosis of glaucoma, we developed a new fundus image processing system that measures the optic disc structures from the fundus video image and enhances the RNFL. The design and function features are discussed in detail. Clinical application shows that the multifunctional system is accurate in measurements and easy to operate, providing a new approach to the early diagnosis of glaucoma. PMID- 8001450 TI - [Visual symptoms of sellar tumors: a report of 407 cases]. AB - The common primary symptoms of sellar tumors are visual impairment and field defects associated with the anatomic relationship between the sella turcica and the visual route, and the patients often consult the oculist first. The authors reviewed 407 cases of sellar tumors at their hospital during the recent 10 years and analyzed the characteristics of these patients to present the general clinical patterns and main points for diagnosis of this disease. PMID- 8001451 TI - [A report of the quantitative determination of relative afferent pupillary defect in central retinal vein occlusion]. AB - Relative afferent pupillary defect (RAPD) indicates injury to the afferent pupillary nerve fibers anterior to the optic chiasma. The light attenuator composed of 2 optical polarizers was utilized to determine the RAPD quantitatively in 32 cases of central retinal vein occlusion (CRVO). In 13 cases with ischemic CRVO, 77% manifested an RAPD of 0.9 log unit or over and none less than 0.75 log unit. In contrast, among 19 cases with non-ischemic CRVO, 84% showed an RAPD of 0.65 log unit or less and none over 0.75 log unit, suggesting that RAPD was a sensitive index for differentiating ischemic from non-ischemic CRVO. PMID- 8001452 TI - [Retinal arteriolar annulus and its function]. AB - Histological special staining and dehydrogenase histochemical techniques were used to observe the structure and staining reactions at the junctions of side-arm branches of retinal arteries in man and several species of animals. Annular stains occurred at the junctions of side-arm branches in cat, rat, pig and dog, but not in man, rhesus monkey and beef with PAS, Masson's and elastic Van Gieson's (EVG) stains. However, in man and all the animals studied, they can be demonstrated with dehydrogenase histochemical techniques, i.e. succinate, malic and lactic dehydrogenases (SDH, MDH and LDH). The tissue components of retinal arteriolar annulus and its role in control of retinal circulation were discussed. PMID- 8001453 TI - [The relationship between stereoacuity and contracted visual field]. AB - The stereoacuity (SA) was measured by means of the Titmus test, Random Dot E stereotest and Yan's stereoscopic test charts in 90 cases of glaucoma or retinitis pigmentosa with visual field contraction and 28 normal subjects. Significant reduction in SA was observed in all patients with contracted visual field, and markedly so (> 130") in cases with bilateral or unilateral tubular vision. The SA was reduced with visual field loss of over 30% and there was a positive correlation between the SA reduction and the area of visual field loss. PMID- 8001454 TI - [Development of visual function in infants and children]. AB - The development of P1 component of VEP was studied in 150 normal infants and children between the age of 2 weeks and 9 years. The results indicates that the VEP consists of simple positive waves within 8 weeks following birth, the latencies of P1 components shorten dramatically from 2 to 4 months, the development of the latencies of low, medium and high spatial frequencies of P1 components reaches adult levels in infants and children of 4 months, 4 years and 9 years, respectively and the VEP amplitudes of infants and children are significantly higher than those of adults. Based on the results of our research, the development of visual function can be divided into 3 phases: the first, within 4 months following birth; the second, 5 months to 4 years and the third, 5 to 9 years. PMID- 8001455 TI - Use of human leukocyte-specific monoclonal antibodies for clinically immunophenotyping lymphocytes of rhesus monkeys. AB - The rhesus monkey (Macaca mulatta) is an important experimental animal frequently utilized for studies of infectious diseases, immunity, hematopoiesis, and transplantation. Since the structure of cell surface molecules is phylogenetically conserved, monoclonal antibodies raised against human leukocyte antigens can sometimes recognize the homologous determinant on monkey leukocytes. To facilitate better utilization of this animal model, we tested 89 commercially available monoclonal antibodies which define 27 human cell surface antigens for reactivity with rhesus monkey PBL. Certain antigens which delineate clinical useful lymphocyte subsets such as CD2, CD4, CD8, CD14, CD16, CD20, and MHC class II are apparently well conserved since most human cell-specific antibodies identified the homologous cell subset in monkeys. However, other antigens such as CD3, CD19, CD45, and CD56 were identified infrequently by human cell-specific antibodies. FITC-modification of antibodies which had no effect on their binding to human cells occasionally inhibited antibody binding to monkey cells. Nevertheless, an adequate number of cross-reactive monoclonal antibodies was identified to allow gating of lymphocytes for accurate flow cytometric analysis and quantitation of the major lymphocyte subsets of the rhesus monkey. The T lymphocyte subset distribution in blood and lymphoid tissue of rhesus monkeys was similar to man. However, the B subset was significantly larger in monkeys. The daily variation in absolute PBL subset size was marked and found to be due mainly to daily fluctuations in total lymphocyte number. PMID- 8001456 TI - Rapid fluorescence in situ hybridization with repetitive DNA probes: quantification by digital image analysis. AB - Fluorescence in situ hybridization (FISH) has become an important tool not only in cytogenetic research but also in routine clinical chromosome diagnostics. Here, results of a quantification of fluorescence signals after in situ hybridization with repetitive DNA probes are reported using a non-enzymatic hybridization technique working with a buffer system not containing any formamide or equivalent chemical denaturing agents. Following simultaneous denaturation of both cells and DNA probes, the renaturation time was reduced to less than 30 min. For one of the DNA probes reasonable FISH-signals were even achieved after about 30 s renaturation time. In addition, the number of washing steps was reduced drastically. As a model system, two repetitive DNA probes (pUC 1.77, D15Z1) were hybridized to human metaphase spreads and interphase nuclei obtained from peripheral blood lymphocytes. The probes were labelled with digoxigenin and detected by FITC-anti-digoxigenin. The hybridization time was reduced step by step and the resulting fluorescence signals were examined systematically. For comparison the pUC 1.77 probe was also hybridized according to a FISH protocol containing 50% formamide. By renaturation for 2 h and overnight two FISH signals per nucleus were obtained. Using shorter renaturation times, no detectable FISH signals were observed. Quantification of the FISH signals was performed using a fluorescence microscope equipped with a cooled colour charge coupled device (CCD) camera. Image analysis was made interactively using a commercially available software package running on a PC (80486). For the pUC 1.77 probe the major binding sites (presumptive chromosomes 1) were clearly distinguished from the minor binding sites by means of the integrated fluorescence intensity. For the two (pUC 1.77) or four (D15Z1) brightest spots on the metaphase spreads and in the interphase nuclei hybridized without formamide, integrated fluorescence intensity distributions were measured for different renaturation times (0.5, 15, 30 min). The intra-nuclear variation in the intensity of the two brightest in situ hybridization spots appeared to be slightly higher (CV between 16 and 32%) than the corresponding variation in the metaphase spreads (CV between 10 and 19%). For the D15Z1 probe FISH signals were detected after hybridization without formamide and 15 min and 30 min renaturation. Always four bright spots were visible and tentatively assigned on the metaphase spreads (presumptive chromosome 15 and 9). The intensity variation of each pair of homologues in a metaphase spread showed a CV of 14 or 15%, respectively, for the presumptive chromosome 15, and 8 or 9%, respectively, for the presumptive chromosome 9. PMID- 8001457 TI - Flow-cytometric quantification in human gliomas of alpha satellite DNA sequences specific for chromosome 7 using fluorescence in situ hybridization. AB - Cell suspensions prepared from freshly frozen tissue specimens were used to examine aberrations in the number of chromosome 7 signals in 10 human gliomas. Nuclear DNA was hybridized in vitro with an alpha satellite DNA probe specific for the centromeric regions of chromosome 7, using fluorescence in situ hybridization (FISH). The intensity of the fluorescence signal from the hybridized probe was measured, together with the nuclear DNA content, by flow cytometry. The mean probe fluorescence of all nuclei was compared to the mean copy number per nucleus found with microscopic scoring. Moreover, the mean probe fluorescence ratio of DNA aneuploid nuclei relative to DNA diploid nuclei (FISHa/FISHd) was calculated to determine how the numerical aberration of chromosome 7 signals contributes to the DNA ploidy of the sample. The results from the flow-cytometric analysis and from microscopic evaluation were compatible. One of four tumors with DNA diploidy had a higher average intensity of FISH signal and a broader coefficient of variation in FISH signal than normal brain tissue; this was shown to be due to the gain of chromosome 7 signals. Although FISHa/FISHd correlated with DNA indices (P < 0.01), there were some disparities, probably due to other complex genotypic associations involving several gains or losses of chromosomes. Thus gain of chromosome 7 in gliomas is related to both DNA ploidy change and chromosome specific gain. It is concluded that flow-cytometric quantification of FISH is useful in investigating numerical aberrations of chromosomes and nuclear DNA content simultaneously. PMID- 8001458 TI - Scanning microspectrofluorometry of rhodamine 123 in multidrug-resistant cells. AB - Scanning microspectrofluorometry has been developed to perform the mapping of fluorescence spectra from all locations in a living cell. This new method has been applied to study the molecular environment of rhodamine 123 (R123) in sensitive (K562, CEM) and multidrug-resistant (K562-R, CEM/VLB100) tumor cells. All cells exposed to R123 showed a similar distribution of fluorescence in the perinuclear region. A lower cytoplasmic fluorescence intensity corresponding to a reduced drug accumulation was observed in resistant cells, as expected in the multidrug resistance process. Fluorescence emission spectra of R123 are useful to probe the polarity of the R123 environment. Thus, fluorescence spectra of R123 treated cells have been analyzed as a linear combination of model spectra: R123 in water and R123 in tensio-active Triton X-100. In sensitive cells, emission spectra of R123 underwent a red shift, equivalent to those observed in isolated coupled mitochondria. This suggests the formation of a complex in hydrophobic sites. In contrast, R123 spectra were less shifted in resistant cells, showing two types of both hydrophobic and hydrophilic binding sites. This could be related to an intracellular redistribution of R123 in resistant cells. PMID- 8001459 TI - Expression of proliferation-associated antigens (PCNA, p120, p145) during the reentry of G0 cells into the cell cycle. AB - Flow cytometric bivariate analysis was used to evaluate the expression of PCNA, p120, and p145 during the G0 reentry of CHO-K1 cells into the cell cycle. CHO-K1 cells were placed in a G0-like state using serum depletion and stimulated to reenter the cell cycle by replating into fresh, serum-containing medium. At discrete intervals after stimulation, replicate samples were stained for either PCNA, p120, or 145; stained for DNA (Coulter DNA-Prep); evaluated on the EPICS Profile I; and analyzed on the EPICS ELITE workstation. PCNA stained less than 10% of the G0 cells; in contrast, however, 30-35% of the G0 cells were positive for p120 and p145. Eight hours after stimulating G0 cells to reenter the cell cycle (during G0/G1), p120 reached 88% positivity, while p145 and PCNA were 63% and 30% positive, respectively. Cells in S phase (12 and 16 h following G0 stimulation) were greater than 90% positive for all three antigens. PCNA had the greatest change throughout the G0 reentry process, both in percentage positive and quantitatively (mean channel fluorescence). This report indicates that all three proliferation-associated antigens studied are differentially expressed during the reentry of G0 cells into the cell cycle. Furthermore, these antigens may be useful in the early detection of G0 recruitment. PMID- 8001460 TI - Flow cytometric detection and quantitation of the epidermal growth factor receptor in comparison to Scatchard analysis in human bladder carcinoma cell lines. AB - The epidermal growth factor receptor (EGFR) is considered a tumor-related marker with potential diagnostic and prognostic value. In order to assess the sensitivity of flow cytometry to detect EGFR and to quantify receptors objectively, two human bladder carcinoma cell lines with different urothelial differentiation, RT4 and J82, were grown in vitro, and their membrane EGFR content was measured by flow cytometry. Exponential monolayers showed decrease of EGFR content after 20 min pulses with 10 ng/ml EGF in medium, as detected with the antibody EGFR1 in a double staining technique with propidium iodide for DNA evaluation. Further decrease of green fluorescence intensity was seen in cells constantly exposed to EGF. Absolute receptor numbers were determined by Scatchard analysis with radioactive EGF and resulted in relatively low receptor numbers for both cell lines (approximately 3-4 x 10(4) EGFR/cell), as well as one affinity class. These findings could be matched by absolute receptor quantification by flow cytometry, adding beads with defined antigenic sites (Quantum Simply Cellular, Microbead Corporation) to the cell suspension for staining. Our data suggest that flow cytometric EGFR detection and quantitation may be supplied to in vivo tumor samples and that measurements by multiparameter analysis may define subpopulations valuable for tumor diagnosis and judgment on tumor progression. PMID- 8001461 TI - Flow cytometric determination of the multidrug-resistant phenotype in acute leukemia. AB - Expression of the multidrug-resistant (MDR) phenotype was investigated in acute leukemia using a monoclonal antibody (HYB-241) directed against a cell surface epitope of the 180 kd P-glycoprotein (gp180) by flow cytometric analysis of clinical samples. Samples from sixty-four patients were tested (37 with acute myelocytic leukemia, 20 with acute lymphocytic leukemia, and 7 with blastic chronic myelocytic leukemia). A D value (derived from Kolmogorov-Smirnov test) greater than 0.15 was considered positive (+). Eight of 32 newly diagnosed patients were positive for gp180 compared with 22 of 32 relapsed/refractory (R/R) patients (P < 0.001). Of the new patients, vinca/anthracycline-based induction therapy failed in 3/6 gp180(+) and 5/18 gp180(-) patients. In the R/R group, 15/16 gp180(+) and 3/6 gp180(-) patients failed to achieve complete remission (P < 0.05). In vitro drug accumulation studies performed with verapamil failed to show a correlation with clinical response. However, in a subset of patients, a striking correlation (r = .97, P = .001) was noted between the presence of gp180 as determined by the D value and the functional activity of the P-glycoprotein as expressed by increased daunorubicin accumulation in the presence of verapamil. The results suggest that 1) newly diagnosed patients can express gp180, 2) P glycoprotein is expressed in 69% of R/R patients, 3) response in R/R patients is effected by the presence of gp180, and 4) expression of gp180 is highly correlated with its function as a drug-efflux pump in a subset of the patients studied. The complexity of clinical drug resistance is underscored by the finding that the MDR model is not applicable to all cases. In such instances, other mechanisms may play a predominant role. PMID- 8001462 TI - Fluorescence lifetime measurements in a flow cytometer by amplitude demodulation using digital data acquisition technique. AB - We have developed a method for fluorescence lifetime measurements in a flow cytometer based upon the amplitude demodulation of the fluorescence signals using digital data acquisition techniques. Amplitude demodulation is one of the two methods by which excited state lifetimes may be investigated in the frequency domain. The other method involves the phase-shift measurements. In frequency domain measurement techniques, the amplitude-demodulation and phase-shift data serve mutually complementary roles to enhance the analytical capabilities of the measurements. The purpose of having amplitude demodulation measurement capability is to obtain information that supplements, rather than replaces, that obtained by the phase-shift method alone. Application of amplitude demodulation measurements has been widely explored in static, cuvette-based, frequency domain systems. However, due to time dependence of the amplitude of the modulated fluorescence signal in a flow cytometer, the amplitude demodulation measurements in flow turns out to be more complicated than similar measurements in a static system. The goal of the present work is to explore the problems involved in amplitude demodulation measurements in flow (using digital method), through detailed theoretical modeling and use the model to develop a practical method that can be incorporated into a flow cytometer to measure amplitude modulation lifetimes. We experimentally verify the amplitude demodulation measurement capability of this method using fluorescent microspheres. The experimental measurements show good agreement with static frequency-domain measurements on microspheres in bulk suspensions. PMID- 8001463 TI - [Symptoms and endocrinologic features of catecholamine-secreting tumors. Results in 106 consecutive patients]. AB - The clinical and endocrinological features in 106 patients (40 men, 66 women, mean age 48 +/- 14.3 years) treated between 1973 and 1993 for proven catecholamine-secreting tumours (phaeochromocytoma: n = 88, paraganglioma: n = 10, adrenal medullary hyperplasia: n = 8) were analysed. The most frequent symptoms were palpitations (68%), severe sweating (53%) and headache (42%). 10% of patients were symptom-free. 58% of patients had consistently raised blood pressure, and 20% of patients suffered paroxysmal blood pressure crises. However, 22% of patients did not have hypertension. Raised urinary catecholamines were found in more than 95% of cases; MIBG (metaiodobenzylguanidine) scintigrams were abnormal in more than 85% of cases. Patients with catecholamine-secreting tumours do not always have "classical" features. The high sensitivity of properly performed catecholamine measurement on plasma and urine has made dangerous stimulation and suppression tests obsolete. PMID- 8001464 TI - [Incompatibility of tuberculosis therapy in a patient with AIDS]. AB - A man with advanced HIV infection (CD4 lymphocytes 90/microliter, CD4/CD8 ratio 0.2) was admitted to hospital with fever, cough and weight loss. The radiological and bronchoscopic findings, together with the presence of acid-fast bacilli in the sputum, pointed to open pulmonary tuberculosis caused by Mycobacterium tuberculosis, a diagnosis confirmed by histological examination and culture. Quadruple antibiotic therapy with isoniazid (INH), rifampicin (RMP), ethambutol (EMB) and amikacin was immediately begun and was at first clinically successful. Ten days later, however, a rash appeared; it was ascribed to RMP (anaphylactoid reaction after re-exposure). All the other first-line drugs tried during the ensuing eight months evoked severe adverse reactions (INH: rash and itching; amikacin: hearing impairment and tinnitus; EMB, pyrazinamide, prothionamide, p aminosalicylic acid: rash and itching). Treatment was nevertheless clinically and microbiologically successful, and the patient insisted upon a 2 1/2 months' rest without therapy. This period was followed by extrapulmonary spread (severe arthritis of the elbow) and recurrence of pulmonary tuberculosis. The tubercle bacilli were sensitive to all the drugs so far employed. Renewed and lasting control of the infection was achieved only by continuous administration of steroids (prednisolone 10 mg twice daily) in conjunction with an unconventional antibiotic regimen consisting of amikacin, protionamide, terizidone, clarithromycin and sparfloxacin for some five months. Because of an episode of cerebral convulsions during treatment of cytomegalovirus retinitis with ganciclovir, the terizidone was discontinued (it was suspected of interacting with ganciclovir). The patient has had no more fits and sputum culture has remained negative for six months. PMID- 8001465 TI - [Reversible thrombocytopenia due to digitoxin overdose]. AB - A 65-year-old woman, known to have peptic ulcers, developed nausea and retching. Clinical examination demonstrated pain on pressure in the epigastrium with otherwise normative findings for age. Two gastric ulcers and gastritis with erosions were seen at endoscopy. The patient, who was being treated with digitoxin for heart failure, reported having taken up to four digitoxin tablets (0.07 mg each) daily because she had insomnia. The plasma digitoxin level was between 150 and 160 nmol/l (therapeutic range 17-33 nmol/l), while the ECG showed no signs of digitalis intoxication. Initially the platelet count was 40,000/microliter: there had been no history of thrombocytopenia or symptoms of abnormal haemostasis. Other laboratory tests were within normal limits. After digitoxin had been discontinued, the platelet count rose without further treatment to 373,000/microliter 3 weeks after hospital admission by which time the digitoxin level had fallen to 48.9 nmol/l. The gastrointestinal symptoms regressed completely on treatment with omeprazole (40 mg three times daily for 8 days) and ranitidine (150 mg twice daily). PMID- 8001466 TI - [Therapy of acute pancreatitis]. PMID- 8001467 TI - [Pathophysiology of myocardial blood flow. II. Postischemic contractile dysfunction ("stunned" myocardium)]. PMID- 8001468 TI - [Secondary neoplasia after immunosuppression]. PMID- 8001469 TI - [ERCP for known pancreatic pseudocysts]. PMID- 8001470 TI - [Lead poisoning caused by red lead in paprika powder]. PMID- 8001471 TI - Electrophysiologic analysis of snap amplitude in orthodromic and antidromic studies. AB - In 1966, Buchthal and Rosenfalk established that the sensory nerve action potential (SNAP) amplitude increased with increasing number of nerve fibers. Lambert and Dyck's in vitro study of the sural nerve, however, found the SNAP amplitude of a single fascicle was equivalent to the SNAP amplitude of the entire nerve. The current study confirmed Buchthal and Rosenfalk's original findings, and discovered an in vivo equivalent to Lambert and Dyck's findings. Ten subjects were used as their own controls. Orthodromic stimulation of both the index and middle fingers stimulated individually versus simultaneously revealed a significant increase in amplitude (p < 0.001). When the recording and stimulating electrodes were reversed, without physically changing the electrodes on the subject, there was no significant difference between the antidromic SNAP amplitudes recorded from separate fingers, or from both fingers simultaneously. Although in both cases the number of recorded nerve fibers approximately doubled, the effect on the SNAP amplitude was very different. This seemingly paradoxical result can be explained by electrophysiologic differences in the recording methods, without using the concept of fiber density. PMID- 8001472 TI - The ankle jerk and the tibial H-reflex: a clinical and electrophysiological correlation. AB - In an attempt to correlate the tibial H-reflex with the ankle jerk, we evaluated 130 reflexes in 65 patients (35 men and 30 women). All the ankle jerks were graded by one of the authors (BK) without the knowledge of the H-reflex results. The maximal H-reflex amplitude, and the maximal H/maximal M amplitudes correlated in a positive fashion with the ankle jerk (r = 0.75 and 0.69 respectively). In contrast, there was no correlation between the H-reflex latency and the ankle jerk (r = -0.11). We conclude that, in most situations, the tibial H-reflex amplitude and the ankle jerk correlate well; their discordance is infrequent (11.5%). PMID- 8001473 TI - Follow-up investigations of peripheral facial palsy by transcranial magnetic stimulation. AB - Twenty-three patients (10 men, 13 women; age: from 23 to 81 years, mean 52 years) with Bell's palsy were investigated by magneto-electrical stimulation in order to evaluate the usefulness of this method for prognostication. At each examination the facial nerve was electrically stimulated, and an orbicularis-oculi-reflex was elicited. Follow-up investigations were possible in 13 patients. All patients showed pathological long- and short-latency responses at the first examination. The blink reflex examination revealed a pathological result in all cases. The responses to electrical stimulation were pathological only in 35%. The follow-up examinations revealed that the analysis of the short-latency response did not give a prognostic information. In contrast, maintained elicitation of the long latency response pointed to a favourable prognosis. In follow-up investigations, the increase of amplitude and the decrease of latency of the long-latency response correlated with a complete recovery, while the decrease of amplitude and the increase of latency correlated with a partial recovery. The improvement of the responses in magnetic stimulation preceded the clinical improvement. By using magnetic stimulation, an early registration and evaluation of the course of Bell's palsy are possible. PMID- 8001474 TI - Explanation of physiological muscle tremor. AB - This paper attempts to explain physiological muscle tremor as a protective measure against an unusual limb posture. It emphasizes that most of the events in the stretch reflex loop give rise to feedback signals that are transmitted to a supraspinal tremor generator driver which integrates the signals, drives an appropriate spinal tremor generator and stops the events in the stretch reflex loop. The unusual posture and its attendant feedback are effectively abolished and this consequentially eliminates the physiological muscle tremor. PMID- 8001475 TI - Evidence of interaction between human lumbosacral and cervical neural networks during gait. AB - Changes in H-max amplitude resulting from alteration in arm position have been used with changes in gait double support durations resulting from similar changes in arm posture to investigate interaction, if any, between the lumbosacral and cervical neural networks in seven normal subjects. Since the reflex and gait responses of each lower limb were altered by changes in upper limb position, it was suggested that in humans also, there may be interaction not only in a static situation, but also during gait between the lumbosacral and cervical neural networks. The responses of the right leg were always greater than those of the left leg irrespective of the arm position; This retention of inter-limb relation may indicate a dominance of the lumbosacral neural network over its cervical counterpart. PMID- 8001476 TI - Electrophysiological studies (MNCV and H-RL) in twin babies. AB - Twenty-six fullterm and eight preterm babies born of twin pregnancies were studied. Offsprings were subjected to measurements of weight, crown heel length and head circumference along with motor nerve conduction velocity (MNCV) and H reflex latency (H-RL) at right median nerve. The preterm twins had significantly lower MNCV and higher H-RL. The electrophysiological parameters did not vary in first and second born twins as well as in heavier and lighter twins. Three pairs of twins were available for follow-up study. PMID- 8001477 TI - Influence of hip and knee joint angles on excitation of knee extensor muscles. AB - The purpose of this study was to test if (and how) maximal excitation of the knee extensor muscles rectus femoris (RF), vastus lateralis (VL) and vastus medialis (VM) is influenced by knee and/or hip joint angles. Excitation was quantified using surface electromyography. Isometric knee extensions were performed at systematically varying knee and hip joint configurations using a strength testing machine. The results indicate that excitation of the one-joint knee extensor muscles (VL and VM) depends systematically on hip joint angles. In particular, excitation levels are higher at hip joint angles of 90 degrees (sitting) and 180 degrees (lying) compared to intermediate hip joint angles (112 degrees, 135 degrees, 157 degrees). Furthermore, it was found that excitation of all knee extensor muscles tested is higher near full knee extension (170 degrees) compared to an intermediate knee joint angle (130 degrees). Since knee extensor moments are much smaller at knee joint angles of 170 degrees compared to those at 130 degrees, it is speculated that the high excitation observed near full knee extension constitutes a neurophysiological compensation mechanism for the reduced force production ability of the muscles at this joint configuration. PMID- 8001478 TI - Evaluation of cervical radiculopathy by cervical root stimulation. AB - For precise evaluation of cervical radiculopathy, cervical root stimulation (CRS), conventional electromyographic (EMG) studies, nerve conduction velocity (NCV) studies and F responses were done in 32 patients with clinical symptoms and signs of cervical radiculopathy. While performing CRS, a monopolar needle was inserted into the paraspinal muscles, and the compound muscle action potentials (CMAPs) in the biceps, triceps and abductor digiti minimi muscles were recorded. Conventional EMG was abnormal in 18 (56.2%), whereas CRS was abnormal in 25 (78.1%). Among the 25 patients with positive CRS tests, 13 received surgical decompression for cervical root compression caused either by a cervical disc or by foramen narrowing due to spondylosis. Only 10 out of 13 (76.9%) had abnormal conventional EMG findings. CRS provides a sensitive method for making a direct evaluation of proximal root conduction and is a good aid for pre-surgical evaluation of cervical radiculopathy. PMID- 8001479 TI - Posterior interosseous syndrome in acute Guillain-Barre syndrome. AB - Four cases presenting with posterior interosseous nerve syndrome (PIS) in the early period of acute Guillain-Barre syndrome (GBS) are described. The characteristic signs of PIS, consisting of finger extension inability, partial loss of power in wrist extension, and radial deviation during attempted wrist extension were demonstrated bilaterally. Radial nerve conduction study revealed a fall in of compound muscle potential amplitude after proximal stimulation. The signs of PIS became indistinguishable during the course of the illness; this was due to further progression of the forearm weakness veiling the syndrome in some patients, or recovery following plasmapheresis in others. Three of them were amateur sportsmen, in whom active supination-pronation of the forearm was probably responsible for this particular presentation. PMID- 8001480 TI - Neurogenic impotence: diagnostic value of nerve conduction studies, bulbocavernosus reflex, and heart rate variability. AB - In a group of 10 neurogenic impotent patients the diagnostic sensitivities of peripheral nerve conduction, bulbocavernosus reflex latency, and heart rate variability have been compared. The bulbocavernosus reflex latency appears as the least affected parameter, while nerve conduction and heart rate variability measured during hyperventilation and expressed as the percentage of the RR interval variation-show similar diagnostic yields. PMID- 8001481 TI - The carpal tunnel syndrome. Relationship between median distal motor latency and graded results of needle electromyography. AB - Needle Electromyography (NEMG) was performed in 228 patients who had been diagnosed by means of motor and sensory median nerve conductions of having Carpal Tunnel Syndrome (CTS). Evaluating abnormal spontaneous muscle activity (fibrillations, positive sharp waves, fasciculation potentials and myokymic discharges) and recruitment pattern, 51.7% of them showed abnormal NEMG. According to the amount of abnormality found, the studies were classified into: normal, grade 1, grade 2 and grade 3. Median Distal Motor Latency (DML) to APB was prolonged beyond the upper confidence limit in 155 (68%) hands, showing a mean value of 5.69 +/- 2.79 msec. Statistically significant difference (p < 0.001) of DML mean value among patients with a NEMG "normal", "grade 1" or "grade 2" have been found. We revise previous reports about NEMG on the CTS and discuss practical consequences of our findings. PMID- 8001482 TI - Biliary stenting in benign biliary stenosis complicating chronic calcifying pancreatitis. AB - This a retrospective study of 19 patients presenting with chronic pancreatitis and benign stenosis of the common bile duct, who were followed up for periods ranging from 13 months to 48 months after biliary stenting (average 18 months). There were 18 men and one woman, aged between 38 and 65 years (average 49 years). The mean duration of the disease before stenting was seven years (range 1-25 years). Symptoms were present in ten patients: obstructive jaundice in four cases, cholangitis in three cases, and biliary colic in three cases. Nine patients without clinical complaints presented with chronic cholestasis. Endoscopic retrograde cholangiopancreatography (ERCP) showed 15 long, regular stenoses of the intrapancreatic course of the common bile duct, three short stenoses located at the upper margin of the head of the pancreas, and one biliary stenosis associated with peripheral compression by a cyst of the head of the pancreas. Forty endoscopic biliary stenting procedures were performed in the 19 patients over a six-year period. Successful insertion of the prosthesis was achieved in 39 cases. Two complications occurred: one duodenal ulceration and one stent migration into the bile duct. The mean duration of biliary stenting was ten months. Only two patients (10%) had complete clinical, biological, and radiological recovery. Complete failure of biliary stenting was observed in six patients (31%). Eleven patients (59%) had partial results: six (31%) had biological improvement although the biliary stricture persisted, and five were clinically asymptomatic but had cholestasis, and still presented with biliary stenosis in four cases.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8001483 TI - Extracorporeal shock-wave lithotripsy of pancreatic duct stones: immediate and long-term results. AB - To study the efficacy of extracorporeal shock-wave lithotripsy (ESWL) of pancreatic duct stones, seventeen patients (mean age: 42 years) with recurrent attacks of abdominal pain as a result of chronic calcifying pancreatitis were treated with this method. In all cases, endoscopic removal of the stones proved impossible. When there was fragmentation, the remaining calculi and fragments either evacuated spontaneously, or attempts were made to extract them endoscopically, followed by flushing. In 13 patients (76%), fragmentation of stones was achieved, and 11 of these patients had dramatic pain relief directly after ESWL (65%). However, complete ductal clearance of stones was achieved in only seven patients (41%); at the last follow-up (12-59 months after ESWL, mean: 30 months), all seven were free of symptoms. Of the six patients with stone fragmentation without ductal clearance, three were operated on because of recurrent complaints. The only complication due to the procedure was an exacerbation of pancreatitis in one patient, which was treated conservatively. If pancreatic stones cannot be removed endoscopically, ESWL seems to be preferable to surgery, which may still be performed in case of failure. It seems important to achieve ductal clearance and not merely stone disintegration in order to obtain the desired long-term clinical effects. PMID- 8001484 TI - Endoscopic ultrasonography with a linear-type echoendoscope in the evaluation of 94 patients with pancreatobiliary disease. AB - The purpose of this study was to evaluate a new endoscopic ultrasonography (EUS) device using a curved-array transducer with a 120-degree sagittal scan angle in the diagnosis of pancreatobiliary disease. From October 1991 to June 1993, 94 patients underwent EUS to assess radiologically detected anomalies (62 cases), tumors of the papilla of Vater (seven cases) and laboratory findings demonstrating cholestasis of unexplained origin (25 cases). In 41 cases, surgery was performed after EUS, and in 40 cases ERCP was also performed. The EUS diagnosis of chronic calcifying pancreatitis was confirmed by ERCP in 14 of 18 patients. In 30 cases, EUS detected a pancreatic tumor. In 26 of these patients, surgery was performed, confirming EUS findings regarding tumor size, portal, mesenteric, and splenic invasion, and lymph-node involvement in 20 of 25 pancreatic carcinomas (80%). In five of seven patients in whom EUS detected ampullary carcinoma, cephalic duodenopancreatectomy was performed, and the histology of the surgical specimen confirmed the diagnosis in all five. In 25 patients presenting with cholestasis of unexplained origin, EUS provided the diagnosis in 22 cases (88%). EUS using a curved-array transducer appears to be an effective diagnostic method for pancreatobiliary lesions. These results should be further evaluated in a larger series of patients. PMID- 8001485 TI - Endosonographically guided fine-needle aspiration puncture of paraesophagogastric mass lesions: preliminary results. AB - Mass lesions adjacent to the gastroesophageal wall can be visualized in detail by endoscopic ultrasonography. However, in many patients tissue diagnosis of these mass lesions is urgently required. We evaluated the efficiency of transmural fine needle aspiration puncture guided by endosonography for cytological confirmation of such mass lesions. Endosonographically guided transmural fine-needle aspiration (EUS-guided FNA) puncture was performed in 12 patients with extrinsic mass lesions adjacent to the gastro-esophageal wall. In seven patients a malignant tumor and in four patients a benign lesion, were identified by EUS guided FNA puncture, while in one patient no diagnostic tissue specimen could be obtained. No complications were observed. The cytological result of a malignant lesion was confirmed in six patients either by autopsy (n = 3), resection of tumor metastasis (n = 1) or by demonstration of a local recurrence of a previously histopathologically diagnosed carcinoma (n = 2), while the benign cytological results in four patients were confirmed by a follow-up period of at least 13 months (n = 3) and appropriate diagnostic tests (n = 1). It is concluded that EUS-guided FNA puncture is an efficient diagnostic technique for the assessment of malignancy and tissue diagnosis of extrinsic paragastroesophageal mass lesions. An important precondition for the successful performance of transmural EUS-guided FNA puncture is the application of endosonographic transducers with longitudinal scanning in the axis of the endoscope. PMID- 8001486 TI - Long-term experience in Wallstent therapy for malignant choledochal stenosis. AB - During a four-year period up to May 1993, 118 patients (mean age 69 years) with malignant bile duct stenoses were treated with a total of 127 selfexpanding 10-mm metal endoprostheses (Wallstent), most of them endoscopically (n = 102). Technical problems during and shortly after implantation occurred in five cases (4.2%), but could all be solved endoscopically. Serum bilirubin decreased from a mean of 8.0 mg/dl at presentation to a mean of 2.0 mg/dl after stenting. Nineteen patients died within the first three months (5% within the first 30 days); recurrent obstruction, as manifested by recurrent jaundice or cholangitis, or both, was encountered in 14%. Fifty-one patients who survived longer were followed up until death or for a minimum of 12 months (mean follow-up: 12 months). Stent patency rates in this group were 86% (six months), 72% (12 months) and 64% (18 months), survival for these time periods being 63%, 35% and 17%, respectively. No significant stent-related complications were noted; stent occlusion occurred in 12% of patients after a mean of 168 days, and was successfully managed endoscopically (thermal cleaning, implantation of further stents) in all cases. We conclude from our long-term follow-up data that patients surviving longer than three months are the ones most likely to benefit from Wallstent insertion for malignant jaundice. PMID- 8001487 TI - A new miniature ultrasonic probe for gastrointestinal scanning: feasibility and preliminary results. AB - A prototype of a new miniature ultrasonic probe (Aloka) was clinically evaluated in 37 patients with a variety of gastrointestinal lesions. The probe's diameter of 2.0 mm allowed passage through the working channel of conventional endoscopes; the ultrasonic frequencies used were 15 and 20 MHz. Fourteen patients with benign and malignant gastrointestinal tumors, and thirteen patients with a variety of benign conditions, were examined, 12 of whom also underwent conventional endoscopic ultrasonography with side-viewing echoendoscopes. The image quality of the two systems was well comparable, but the ultrasonic penetration depth of the miniprobes was inferior to that of conventional endoscopic ultrasonography (EUS). All but three lesions were adequately visualized by the ultrasonic probe, whereas conventional EUS failed to completely visualize four cases. Of the two ultrasonic frequencies used, we found 15 MHz to be superior, since it provided good image quality and adequate penetration depth. In conclusion, we feel that the probe can be used for EUS indications in the gastrointestinal tract, whereas further technical improvements, such as increasing the penetration depth, are necessary before pancreatobiliary EUS can be carried out. PMID- 8001488 TI - Percutaneous endoscopic polypectomy of gallbladder polyps. AB - We report here our preliminary experience with percutaneous endoscopic polypectomy of gallbladder polyps. Five patients with a total of 17 cholesterol polyps (size: 4-6 mm) and one patient with two gallbladder adenomas (size: 5 mm), four of whom were symptomatic and all of whom refused cholecystectomy, underwent a single-stage procedure under epidural anesthesia. All patients had functioning gallbladders, as assessed by oral cholecystography after stimulation. Following a small incision, the gallbladder was pulled out of the abdominal wall, incised, and a cholecystoscope introduced. The polyps were coagulated at their stalk using microwave irradiation (70-80 mA, 9 sec) and removed for histopathological evaluation thereafter. A catheter was left in situ for ten days. Follow-up for a mean of 11.6 months (8-16 months) showed all patients to be symptom-free and without recurrence of polyps on ultrasonography. Gallbladder function was assessed in five cases by meal-stimulated oral cholecystography, and in one by hepato-iminodiacetate acid (HIDA) scan and was found to be well preserved. The preliminary results warrant further evaluation of this method of removing indeterminate gallbladder polyps. PMID- 8001489 TI - Improved endoscopic management of severe upper gastrointestinal hemorrhage using a new wide-channel endoscope. AB - Problems in emergency endoscopy for upper gastrointestinal bleeding may arise due to blood and food debris preventing proper endoscopic vision and orientation. We present here a new big channel endoscope with a 6 mm suction and drainage channel that achieved complete evacuation of stomach contents in 122 of 123 patients with upper gastrointestinal bleeding, in whom complete gastric cleaning and identification of the bleeding source had proved impossible using standard endoscopes. Gastric emptying using the big-channel endoscope was possible within five minutes in all successful cases. Optimal conditions for therapeutic procedures were therefore provided. The size of the instrumentation channel may open up new indications also for non-emergency endoscopic diagnosis and treatment. PMID- 8001490 TI - Gastrointestinal intramural hematoma, a complication of endoscopic injection methods for bleeding peptic ulcers: a case series. AB - In a prospective study, all patients with peptic ulcer bleeding were documented between February 1984 and April 1992. A total of 227 patients were treated by local injection of epinephrine followed by laser application and injection of polidocanol or fibrin tissue adhesive. In five of these patients, intramural hematomas developing at the former bleeding site one to three days after endoscopic treatment were observed. The presenting symptoms were abdominal pain, nausea, and vomiting. The diagnosis was established by endoscopy, abdominal ultrasound, computed tomography, or laparotomy. In four of our five patients, the bleeding site and hematoma were located in the duodenum. All patients suffered from severe underlying diseases, and showed a clear disturbance of coagulation parameters. In three patients, acute pancreatitis occurred concurrently with the hematoma, probably due to obstruction of the papilla of Vater or compression of the pancreas caused by the hematoma. PMID- 8001491 TI - Transgastric esophagoscopy with antegrade dilation. AB - An 80-year-old man in whom successful dilation of an obstructed esophagus via retrograde esophagoscopy was carried out is reported here. His nutrition had been previously sustained by a feeding gastrostomy tube inserted under radiologic guidance. This gastrostomy stoma was dilated to allow passage of a pediatric gastroscope into the stomach and esophagus. A guide wire was then negotiated past the esophageal stricture, under endoscopic vision and fluoroscopic guidance, into the oropharynx. Savary dilators were then passed over the guide wire perorally to dilate the stenosis. The patient was able to swallow liquids soon after the procedure. The use of Savary dilators over a guide wire introduced by retrograde esophagoscopy has not been previously described. PMID- 8001492 TI - Chronic pancreatitis in 1994: is there a role for endoscopic treatment? PMID- 8001493 TI - New laparoscopic treatment of bleeding Meckel's diverticulum in adults. PMID- 8001494 TI - Endoscopically and histologically documented gastrointestinal lesions in an adult patient with Henoch-Schonlein purpura. PMID- 8001495 TI - Data processing in endoscopy: Endotorace, a new software program for bronchoscopy reporting. PMID- 8001497 TI - Esophageal perforation and variceal banding. PMID- 8001496 TI - Common bile duct dilation in patients with lung neoplasms: can it really be considered a paraneoplastic phenomenon? PMID- 8001498 TI - Delayed perforation after EHT-probe coagulation of colonic angiodysplasias. PMID- 8001499 TI - Congress report on the digestive diseases week 1994 in New Orleans: endoscopic abstracts. PMID- 8001500 TI - MDR1 gene expression in brain of patients with medically intractable epilepsy. AB - Why some patients with seizures are successfully treated with antiepileptic drugs (AEDs) and others prove medically intractable is not known. Inadequate intraparenchymal drug concentration is a possible mechanism of resistance to AEDs. The multiple drug resistance gene (MDR1) encodes P-glycoprotein, an energy dependent efflux pump that exports planar hydrophobic molecules from the cell. If P-glycoprotein is expressed in brain of some patients with intractable epilepsy and AEDs are exported by P-glycoprotein, lower intraparenchymal drug concentrations could contribute to lack of drug response in such patients. Eleven of 19 brain specimens removed from patients during operation for intractable epilepsy had MDR1 mRNA levels > 10 times greater than those in normal brain, as determined by quantitative reverse transcriptase-polymerase chain reaction (RT PCR) method. Immunohistochemistry for P-glycoprotein from 14 of the patients showed increased staining in capillary endothelium in samples from epileptic patients as compared with staining in normal brain samples. In epileptic brain specimens with high MDR1 mRNA levels, expression of P-glycoprotein in astrocytes also was identified. Last, steady-state intracellular phenytoin (PHT) concentrations in MDR1 expressing neuroectodermal cells was one fourth that in MDR1-negative cells. MDR1 expression is increased in brain of some patients with medically intractable epilepsy, suggesting that the patients' lack of response to medication may be caused by inadequate accumulation of AED in brain. PMID- 8001501 TI - Development of epileptic activity in embryos and newly hatched chicks of the Fayoumi mutant chicken. AB - The homozygous Fayoumi strain of epileptic chickens (Fepi) is affected by generalized convulsions consistently induced by intermittent light stimulation (ILS) and by intense sound. Although interictal EEG recordings show continuous spikes and spike and wave activity, desynchronization and flattening (DF) of the EEG are observed during seizures. We have studied development of the epileptic phenotype in embryonic (E) and posthatching (P) Fepi. As compared with those of chicken embryos of a normal strain, no differences were observed in the EEG before embryonic day (E) 16. Clearly differentiated spikes and spike and waves appeared at E17 in Fepi. Metrazol-induced EEG seizures were observed at E16 in normal embryos and at E17 in Fepi. The Fepi showed some characteristics: Spontaneous EEG seizure-like discharges also appeared at E17 but decreased toward hatching; visual or acoustic hyperexcitability developed at E20 together with evoked responses in normal chickens; desynchronization of the EEG, typical of the epileptic seizure of the adult, could be induced by ILS at B20, but ILS- or sound induced generalized motor seizures appeared at P1, a few hours after hatching. Results show that Fepi phenotype reaches full expression at P1, but the electric paroxysms are expressed earlier, paralleling synaptic maturation. PMID- 8001502 TI - Seizures presenting as episodic hypersomnolence. PMID- 8001503 TI - Frontal lobe seizures: electroclinical syndromes. AB - To define further the electroclinical manifestations of frontal lobe epilepsy (FLE), we studied 150 seizures manifested by 24 patients; 18 patients had subdural electrode arrays (SEA). The findings in these patients clearly overlapped presumably reflecting the interconnections between functionally related frontal zones; yet the manner in which the symptoms clustered and the sequence in which they occurred generally indicated the anatomic site of the epileptogenic zone. We divided the patients into three major groups: (a) those with supplementary motor seizures, (b) those with focal motor seizures, and (c) those with complex partial seizures (CPS, psychomotor seizures). Supplementary motor seizures began with tonic posturing of the extremities. Focal motor seizures generally began with conscious contralateral version or unilateral clonic focal motor activity; tonic posturing was noted only late in the seizure. CPS (psychomotor) began with unresponsiveness at onset, followed by staring or unconscious contraversion. We compared frontal lobe seizures with temporal lobe seizures reported previously; oral-alimentary automatisms, repetitive hand movements, or looking around, were more common in temporal lobe seizures, whereas tonic posturing and bicycling movements were more common in frontal lobe psychomotor seizures. PMID- 8001504 TI - Injury and death as a result of seizures. AB - The literature contains little information regarding the incidence of injury or death in the general population caused by seizures. We prospectively surveyed all patient visits to the four emergency departments serving adults in the Halifax Dartmouth metropolitan area (adult population 260,935) from September 1, 1990 to August 31, 1991 to identify patients treated as a result of a seizure. The medical examiner's records were also surveyed for deaths related to seizures. We identified 560 patient visits precipitated by seizures of all types and etiologies except those secondary to acute trauma. Injuries or deaths occurred during 84 of 560 seizures (15%). Sixty-three patients incurred 89 injuries during 77 seizures (some patients had more than one injury, and some patients had injuries on more than one occasion). The incidence of seizures resulting in injury was 29.5 in 100,000 population. The most common injuries were head contusions and head lacerations. Most injuries were minor and required little or no treatment. Deaths occurred during seven seizures (1.2%). The incidence of death as a complication of seizures was 2.68 in 100,000 population. Deaths were not restricted to patients with epilepsy. We conclude that the incidence of seizures causing injury or death in the general population was 32.2 in 100,000 population and that 15% of seizures brought to medical attention resulted in injury or death. Most injuries were minor but seven patients died during seizures, indicating that seizures remain a life-threatening event. PMID- 8001505 TI - Cohort study of incidence of sudden unexplained death in persons with seizure disorder treated with antiepileptic drugs in Saskatchewan, Canada. AB - To measure the incidence of sudden unexplained death in treated persons with epilepsy (SUDEP) and to identify risk factors for SUDEP, a cohort of 6,044 persons aged 15-49 years with more than four prescriptions for antiepileptic drugs (AEDs) was identified from the Saskatchewan Health prscription drug file. To exclude subjects whose sudden deaths (SUDs) might be misattributed to another chronic underlying disease, subjects with hospitalizations for cancer or heart problems were excluded. To exclude subjects without epilepsy, subjects with > 2 year AED treatment followed by AED-free time and subjects receiving < 1 U/day were excluded. The final cohort consisted of 3,688 subjects. Follow-up was started at the first AED prescription listed in the prescription drug file and ended at the earliest of the following: age 50 years, death, or last registration in the Saskatchewan Health. For 153 of 163 deaths occurring in the cohort, copies of anonymized death certificates were obtained and copies of anonymized autopsy reports of potential SUDEP cases were examined. There were 18 definite/probable SUDs and 21 possible SUDEPs, yielding a minimum incidence of 0.54 SUDEP per 1,000 person-years and a maximum of 1.35 SUDEP per 1,000 person-years. SUDEP incidence increased with male sex, number of AEDs ever prescribed, and prescription of psychotropic drugs and was highest in males with a history of treatment with three or more AEDs and four or more psychotropic drug prescriptions. Poisson regression showed a 1.7-fold increase in risk of SUDEP for each increment in maximum number of AEDs administered, a likely surrogate for severity and persistence of seizures. PMID- 8001506 TI - Surgical treatment of an early epileptic encephalopathy with suppression-bursts and focal cortical dysplasia. AB - A case of early epileptic encephalopathy (EIEE) with suppression-bursts or Ohtahara's syndrome, associated with focal cortical dysplasia is reported. Infantile spasms and brief tonic unilateral seizures began on the fifth day of life. Interictal EEG demonstrated an asymmetrical "suppression-burst" pattern with no wake or sleep cycling. Seizures were refractory to all antiepileptic drug (AED) and steroid therapy. Magnetic resonance imaging (MRI) showed right frontotemporal cortical thickening. After three weeks of an ineffective medical treatment a preoperative evaluation with single photon emission computed tomography (SPECT) and electrocorticography (ECoG) was performed to characterize epileptogenic focus. Surgical resection of the precentral area was performed at age 1 month. Neuropathologic examinations confirmed diagnosis of focal cortical dysplasia by identifying cytoarchitectural disarray and ectopic neurons located deep in subcortical white matter. During follow-up, 1-year postoperative the child had a single febrile seizure. Neurologic examination showed minor developmental delay and slight left-sided weakness. PMID- 8001508 TI - Panic attacks mistaken for relapse of epilepsy. AB - Panic attacks, a frequent type of pseudoepileptic seizures, occur more frequently in epilepsy patients than in the general population and are often misdiagnosed, leading to pseudosevere epilepsy. We evaluated 4 patients with a past history of epileptic seizures long in remission who were misdiagnosed as having relapsing seizures although they had fairly typical panic attacks. To avoid unnecessary and ineffective antiepileptic drug (AED) treatment, recurrence of seizures after long remission should be carefully evaluated to identify patients with a panic disorder who require specific treatment. In patients who unexpectedly exhibit seizures after long remission, an accurate retrospective diagnosis of the epileptic syndrome and a precise description of the attack symptomatology should be obtained, if possible with EEG-video monitoring. PMID- 8001507 TI - Asymmetric hypsarrhythmia: clinical electroencephalographic and radiological findings. AB - Twenty-six children (16 boys and 10 girls) with hypsarrhythmia and infantile spasms (IS) were studied at the University of Michigan EEG Laboratory in a 4-year period. Six (2 boys, 4 girls), had asymmetric hypsarrhythmia with a preponderance of both slowing and epileptiform activity over one hemisphere. All 6 had the symptomatic form of IS, 4 with dysplastic conditions, 1 with porencephaly from a cerebral infarct, and 1 with hypoxicischemic encephalopathy. Five children had focal abnormalities on either physical examination or imaging studies. Four had the highest amplitude slowing and most epileptiform activity ipsilateral to the lesion, in 1, it was contralateral. Asymmetric hypsarrhythmia constituted 23% of cases with hypsarrhythmia examined at our EEG laboratory. The significant success in surgical therapy for some children with IS indicates the importance of identifying focal hemispheric abnormalities even if they are not apparent clinically. EEG may suggest focal changes not detected clinically or radiologically. PMID- 8001509 TI - Occipital paroxysmal discharges suppressed by eye opening: variability in clinical and seizure manifestations in childhood. AB - The EEG in childhood epilepsy with occipital paroxysms (CEOP) was termed "distinctive" by Gastaut (1985) and Talwar et al. (1992) and "characteristic" by Herranz Tanarro et al. (1984), which suggests that the EEG is specific and diagnostic for CEOP. However, this hypothesis has been challenged (Newton and Aicardi, 1983; Beaumanoir and Grandjean, 1987). To test this, we reviewed 5,291 EEG reports made in 5 1/2 years in the only tertiary pediatric center in Newfoundland and Labrador. We identified 31 children who had one or more EEGs with occipital spike/sharp waves showing suppression of discharges with eye opening and normal background activity. Six had CEOP, 17 had benign nocturnal childhood occipital epilepsy, 5 had symptomatic epilepsy, 3 had unusual complex partial seizures (CPS), 4 had only provoked seizures, and 2 had no definite seizures. Overlap between seizure types was common. The EEG criteria for CEOP are not very specific. PMID- 8001510 TI - Lesion localization in periodic lateralized epileptiform discharges: gray or white matter. AB - We analyzed the results of neuroimaging studies in patients with periodic lateralized epileptiform discharges (PLEDs) or bilateral independent periodic lateralized epileptiform discharges (BIPLEDs) for localization of lesions in gray or white matter to determine if "cortical isolation" is a critical mechanism in the pathogenesis of this phenomena. We assessed 32 patients who had undergone computed tomography (CT) exclusively and 8 patients who had undergone magnetic resonance imaging (MRI) with or without CT. The superior resolution necessary for adequate lesion localization allowed use of only the MRI scans from the 8 patients. Six patients had scans with cortical and subcortical gray and white matter lesions, and 1 patient had a cortical gray matter lesion only. One patient had an indeterminate scan. No patient had white matter lesions only. Our findings in patients with PLEDs and BIPLEDs correlate with postmortem data in patients with generalized periodic EEG patterns that show consistent localization of lesions in the gray matter. These findings do not support cortical isolation as the critical or sole mechanism in PLEDs or BIPLEDs. PMID- 8001511 TI - Electrical stimulation of the centromedian thalamic nucleus in control of seizures: long-term studies. AB - Five patients with chronic incapacitating seizures averaging 15-5,000/month were selected for study. All patients had more than one seizure type and had received maximal doses of antiepileptic drugs (AEDs). The centromedian thalamic nucleus (CM) was stimulated electrically through bilateral multicontact platinum electrodes stereotaxically placed in CM and connected to internalized pulse generators. Electrophysiologic confirmation of electrode position included thalamically elicited recruiting responses and EEG desynchronization recorded at the scalp. Stimulation parameters were adjusted individually in the range of 450 800-microA intensity, 65 pps, 0.09 ms, in 1-min trains, alternating right and left side stimulation and with 4-min intervals delivered for 2 h/day. Quantitative evaluation included frequency of seizures/month, number of maximal interictal paroxysmal discharges, and frequency of background activities counted in selected scalp EEG samples, taken throughout the observation period (7-33 months). Significance of changes was evaluated by parametric Student's t test. Generalized tonic-clonic seizures (GTC) decreased dramatically, almost disappearing in all cases (p < 0.001), with a significant reduction in interictal paroxysmal discharges (p < 0.01) and a tendency toward an increase in EEG background frequency. Other generalized seizures (atypical absences) decreased significantly, but there was no change in the number of complex partial seizures (CPS). CM stimulation is useful in control of GTC, but its beneficial effect on other seizure types has not been established. PMID- 8001512 TI - Successful epilepsy surgery without intracranial EEG recording: criteria for patient selection. AB - Twenty-two patients with intractable complex partial seizures (CPS) were treated with temporal lobectomy. Eighteen of 22 (82%) are seizure-free while receiving medication, with a mean follow-up time of 4 years. In each case, the clinical seizure pattern, interictal and ictal scalp EEG, magnetic resonance imaging (MRI), neuropsychological testing, and results of the intracarotid amobarbital procedure (IAP) converged to indicate a localized abnormality. None of the patients in this series had mass lesions, vascular malformations, or cortical scars, but 18 of 22 had hippocampal atrophy on MRI and 20 had hippocampal sclerosis (HS) on pathologic examination. We believe it is possible, on the basis of the preoperative evaluation described, to identify a population of epileptic patients who will do very well postoperatively. Such patients do not require invasive EEG monitoring, and they represent approximately 20% of the patients treated surgically in our epilepsy unit in the past several years. PMID- 8001513 TI - Use of saliva in home monitoring of carbamazepine levels. AB - Total carbamazepine (CBZ) levels in serum of 61 epileptic children were compared with saliva levels. Both resting and stimulated saliva was analyzed. The salivary levels were 38.6% of serum CBZ levels. A highly significant correlation was noted (r = 0.89, p < 0.001). Stimulation had no effect on saliva CBZ levels (r = 0.97). Salivary and serum CBZ levels were not affected by storing the samples for 7 days at room temperature. The data indicate that salivary CBZ may provide a reliable alternative monitoring method to Tegretol therapy, especially in children, in whom blood sampling is difficult. Furthermore, the samples may be collected at home and delivered to the laboratory by mail. PMID- 8001514 TI - Melatonin response in active epilepsy. AB - Urinary excretion of 6-sulfatoxymelatonin (aMT.6S), the hepatic metabolite of melatonin, was measured for three consecutive 8-h intervals, beginning at 0600 h, in 30 patients with untreated active epilepsy and in 19 healthy subjects. Excretion of aMT.6S in a 24-h period in patients with active epilepsy was 77.3 +/ 55 nmol (median 68.0, range 8.7-280 nmol), significantly higher (p < 0.05) than that of healthy subjects (49.1 +/- 14 nmol, median 49.0, range 19.7-68.0 nmol). Sequential 8-h urinary aMT.6S excretion rates in patients with active epilepsy were 2.45 +/- 2.8 nmol/h (0600-1400 h), 0.83 +/- 0.5 nmol (1400-2200 h) and 6.38 +/- 5.0 nmol/h (2200-0600 h) as compared with 1.43 +/- 0.8, 1.10 +/- 0.8 and 3.81 +/- 1.3 nmol/h, respectively, in healthy subjects. Analysis of variance (ANOVA) indicated that the difference in total output resulted from greater nocturnal excretion (F = 5.58, p = 0.018). Melatonin production in untreated patients with active epilepsy is increased and has a circadian pattern with a phase difference as compared with that of normal subjects. PMID- 8001515 TI - Chemosensory event-related potentials in patients with temporal lobe epilepsy. AB - We investigated chemosensory functions in patients with temporal lobe epilepsy (TLE) to discover whether olfactory and trigeminal stimuli applied either ipsilaterally or contralaterally to the epileptic focus are processed differently. Twenty-two patients were investigated, 12 of whom had epilepsy with a focus located in left temporal lobe (LTL). The remaining 10 patients had a right temporal lobe (RTL) focus. Input from the trigeminal system was examined by use of CO2; input from the olfactory system was evaluated with vanillin and hydrogen sulfide as stimuli. Chemosensory function was assessed by evaluation of chemosensory event-related potentials (CSERP) and the patients' verbal reports in an odor identification test. In both groups of patients, prolonged CSERP latencies were noted after stimulation of the left nostril with CO2 as compared with stimulation of the right nostril. In contrast, a different pattern emerged for olfactory stimuli. After right-sided olfactory stimulation, latencies were prolonged in patients with right-sided epileptical foci. Similarly, when the left nostril was stimulated in patients with a left-sided focus, CSERP latencies were prolonged. Thus, neocortical processing of olfactory, but not trigeminally mediated information evidently is affected by functional lesions of the temporal lobe. After olfactory stimulation in patients with a right-sided focus, the distribution of amplitudes was different from normal. Moreover, analyses showed nonoverlapping 95% confidence intervals (CI) for latency N1 when vanillin was applied to the right nostril. These results indicate that RTL may play a different role in processing of olfactory information as compared with LTL. PMID- 8001516 TI - Use of ex vivo magnetic resonance imaging to detect onset of vigabatrin-induced intramyelinic edema in canine brain. AB - Vigabatrin (VGB) causes intramyelinic edema (microvacuolation) in brain of dogs and rodent, which has encouraged development of noninvasive methods to monitor for this effect during clinical trials. We report the qualitative ex vivo magnetic resonance imaging (MRI) changes observed in a neuropathology study in dogs to detect time of onset and regression of VGB-induced intramyelinic edema. Beagles were randomly assigned to 18 groups of 6 dogs per group and administered vigabatrin orally (p.o.) at a dose of 300 mg/kg/day (2 males, 2 females) or placebo (1 male, 1 female). Animals were killed and examined at weekly intervals during the 12 weeks of treatment and at 1, 2, 4, 8, 12, and 16 weeks after discontinuation of drug treatment. Myelin microvacuolation in thalamus, hypothalamus, and fornix were noted histologically after 4-5 weeks of treatment. Increases in MRI T2 intensity were observed in hypothalamus after 4 weeks and in thalamus and columns of the fornix after 7 weeks. Both MRI T2 intensity and microvacuolation continued to increase during 12-week VGB treatment. When VGB treatment was discontinued after 12 weeks, both MRI T2 intensity and microvacuolation began to decrease. Sixteen weeks after VGB discontinuation, histopathology had returned to normal and MRI examination demonstrated a marked trend toward reversal of the increased T2 signal intensity. MRI thus has potential as a noninvasive surveillance technique in certain experimental and clinical conditions associated with intramyelinic edema. PMID- 8001517 TI - New parenteral substrates in clinical nutrition. Part I. Introduction. New substrates in protein nutrition. PMID- 8001518 TI - Digestibility of carbohydrates from rice-, oat- and wheat-based ready-to-eat breakfast cereals in children. AB - OBJECTIVE: To study the effect of the presence and quality of dietary fibre in ready-to-eat (RTE) breakfast cereals on completeness of carbohydrate digestion in children and on starch susceptibility to alpha-amylase in vitro. DESIGN: A controlled intervention study. SUBJECTS: Eight 3-8-year-old healthy children. INTERVENTIONS: Completeness of digestion was evaluated by assessing the amount of carbohydrates apparently fermented into the colon using the breath-H2 technique after consumption in random order, of five breakfast tests containing boiled rice (either alone or supplemented with 3 g of lactulose) as reference food, or RTE cereals based on rice (low-fibre), wheat (high insoluble fibre) and oats (high soluble fibre). The potential glycaemic impact of the products was estimated in vitro by assessing starch susceptibility to alpha-amylolysis using an enzymatic dialysis method. RESULTS: Compared to boiled rice and to rice-based RTE cereal, wheat- and oat-based RTE cereals both significantly (P < 0.05) increased the amount of apparently fermented carbohydrates (+1.1 +/- 1.7% of total breakfast carbohydrate fermented for rice, +5.6 +/- 0.9% for wheat and +9.4 +/- 3.7% for oats; mean +/- SEM), calculated using the excess H2 in breath after lactulose as standard. All products showed similar in vitro digestibility, resulting in estimated glycaemic indexes of 117.5 (24.0) for rice, and 105.7 (14.1) for oats based, 128.4 (17.6) for wheat-based, and 129.8 (16.6) [mean 95% CI)] for rice based RTE cereals. CONCLUSIONS: Results suggest that the presence of fibre in RTE breakfast cereals, in particular soluble fibre, increases colonic fermentation in children whereas it seems not to affect glucose availability. PMID- 8001519 TI - Altitude correction for hemoglobin. AB - OBJECTIVE: To propose a correction for the hemoglobin (Hb) increase induced by altitude-associated hypoxia. DESIGN: Part of a national study of nutrition and health of preschool children (0-59 months), based on a stratified, probabilistic, cluster sample. SETTING: Coastal and Andean regions of Ecuador, comprising about 97% of the population, living at altitudes ranging from sea level to 3400 m. SUBJECTS: Subsample of 469 girls and boys, 6-59 months old, with normal iron (Fe) status parameters, i.e serum ferritin > or = 10 micrograms/l, transferrin saturation > or = 12%, zinc protoporphyrin < or = 2.8 micrograms/g Hb. RESULTS: Exponential regression curves are adapted through the Hb values of the children, grouped by altitude ranges, and through the data reported by Hurtado in 1945 for male adults. From these exponential curves, correction factors for Hb are derived for altitudes ranging from sea level to 3400 m. CONCLUSION: The striking parallelism between the hypoxia-induced hemoglobin increase with altitude in young children (girls and boys) and that in male adults strongly suggests that the proposed correction factors for Hb are applicable for all ages and possibly both genders, at least in the Andes. PMID- 8001520 TI - Increase in oxidation resistance of atherogenic serum lipoproteins following antioxidant supplementation: a randomized double-blind placebo-controlled clinical trial. AB - OBJECTIVE: To test the effect of supplementation of diet with ascorbic acid, selenium, alpha-tocopherol and beta-carotene on the oxidation resistance of very low (VLDL) + low density lipoprotein (LDL). DESIGN: A randomized placebo controlled double-masked clinical trial. SETTING: In healthy men aged 30-58 years smoking regularly 15-40 cigarettes/day. SUBJECTS: Forty subjects recruited from the general population, who all completed the study. INTERVENTION: 400 mg of slow release ascorbic acid, 100 micrograms of organic selenium, 200 mg of D-alpha tocopheryl acetate and 30 mg of beta-carotene daily or placebo, 20 men in each group for 3 months. MAIN OUTCOME MEASURES: The oxidation resistance of VLDL + LDL measured by inducing oxidation with copper chloride and, separately, with a combination of haemin and H2O2. RESULTS: In plasma, alpha-tocopherol increased by 72%, beta-carotene by 209%, ascorbate by 45% and selenium by 20% in the supplemented men. The lag time to oxidation increased by 27% [95% confidence interval (CI) 18-35%, P < 0.001] after copper and by 29% (95% CI 12-46%, P = 0.002) after haemin plus H2O2 in the supplemented group as compared to the placebo group by t-tests. The respective net changes in the maximal oxidation velocity were a reduction of 10% (95% CI 1-21%, P = 0.037) after copper and a reduction of 15% (95% CI-1 to 30%, P = 0.070) after haemin and H2O2. CONCLUSIONS: These findings provide further confirmation for the notion that the supplementation of diet with antioxidative vitamins and selenium increases the oxidation resistance of atherogenic lipoproteins in human plasma. PMID- 8001521 TI - The 24-hour recall for Senegalese weanlings: a validation exercise. AB - OBJECTIVE: In Africa, where growth retardation is highly prevalent, the use of expensive and time-consuming diet assessment techniques is a major obstacle to the collection of dietary data on large samples of children. The 24-h recall could be a valuable alternative. Its validity and reproducibility were assessed by comparison with the precise weighing technique. DESIGN & SUBJECTS: Intakes of complementary foods of 45 Senegalese weanlings, aged 11-18 months, were estimated with both techniques on the same days. RESULTS: There was neither a level dependent nor a systematic bias with the 24-h recall for energy and macronutrient intakes. Mean differences between techniques were < 11% of mean intakes. Rank order correlations (r) ranged from 0.60 to 0.81 for energy and macronutrients. However, the analysis by food group showed that the 24-h recall was less precise than the reference, especially for foods from the household common pot (r ranged from 0.31 to 0.61 for rice, oil and fish). In particular, measuring rice intake as a number of 'handfuls' was not satisfactory. The technique needs further improvement for these foods. CONCLUSION: Since it provides unbiased estimates of weanlings' intakes, the 24-h recall can be used for diet surveys of groups of children. Its lack of precision, which could cause attenuation in epidemiological studies, can be compensated by increasing the number of days of survey. This study suggests that a precision equivalent to that of a 1-day weighed survey could be obtained with two 24-h recalls, at a considerably lower cost. PMID- 8001522 TI - Riboflavin status of the elderly: dietary intake and FAD-stimulating effect on erythrocyte glutathione reductase coefficients. AB - OBJECTIVE: The present study was undertaken to investigate the relationship between riboflavin intake and its biochemical status in elderly subjects (> or = 65 years). SUBJECTS: Thirty males and 30 females were randomly selected from a larger sample of free-living elderly residents of Edmonton, Canada. Subjects were contacted through a seniors' service organization and the Medical Officer of Health. Any subject using vitamin supplements or alcohol other than the occasional drink was excluded from the study. DESIGN: Dietary intake was estimated using a 3-nonconsecutive-day food record. Biochemical status was assessed by measuring the erythrocyte glutathione reductase activity coefficient (EGRAC), which is a functional test indicative of metabolic availability of riboflavin. RESULTS: Average daily riboflavin intake of the study population was above the recommended requirement (0.5 mg/1000 kcal). According to the frequently used criterion that an EGRAC value > or = 1.20 is indicative of inadequate riboflavin status, 23% of the males and 7% of the females were classified as being deficient in the vitamin. However, based on the recently suggested normal values (1.30-1.4) for EGRAC, it appeared that all male subjects but one had adequate riboflavin status. CONCLUSION: The criteria used for EGRAC values may affect the interpretation of riboflavin status. It is therefore important that guidelines for EGRAC are standardized for more reliable interpretations. PMID- 8001523 TI - Seasonal variations in vitamins A, C, riboflavin and folate intakes and status of pregnant and lactating women in a rural Gambian community: some possible implications. AB - OBJECTIVE: To relate measured intake of vitamins A, C, folate and riboflavin to biochemical indicators of nutritional status for these micronutrients, and to examine seasonal variations. SETTING: MRC Dunn Nutrition Unit Field Station, Keneba, The Gambia, which has heavy rainfall in August, and little or no rain between late September and mid-June. Data were collected during 1978-80. SUBJECTS: Pregnant or lactating women in a rural farming community whose diet has been studied throughout the year. RESULTS: Mean daily intake of vitamin C varied from virtually nil during the rainy season to about 100 mg/d in May, while plasma ascorbate ranged from 0.2 to 1.2 mg/dl, and breast-milk ascorbate from 2 to 6 mg/dl, changing synchronously with changing intake. Intake of retinol equivalents ranged from 120 micrograms/d in December to 900 micrograms/d in June, and plasma carotenoids showed synchronous fluctuation from 60 to 180 micrograms/dl, whereas plasma retinol was virtually unchanged throughout the year at 30 micrograms/dl. Intake of riboflavin was very low throughout the year, but erythrocyte glutathione reductase activation coefficient ranged from a minimum of 1.5 in July to a maximum of 1.9 between December and March. Obstetric outcome also exhibited seasonal variation with lowest birthweights during the rainy season. Intakes of food energy are assumed to be the major dietary influence on birthweight, but micronutrient intakes and status may have additional effects, and seasonality clearly affects ascorbate intakes by suckling infants. CONCLUSIONS: In countries such as The Gambia seasonality is a major determinant of micronutrient status. However, dietary intake is not the only factor which determines micronutrient status: thus there are seasonal fluctuations in riboflavin status which, for example, may relate to changes in the balance between energy intake and output, rather than to seasonal changes in riboflavin intake. PMID- 8001525 TI - Mental workload and cognitive task automaticity: an evaluation of subjective and time estimation metrics. AB - The evaluation of mental workload is becoming increasingly important in system design and analysis. The present study examined the structure and assessment of mental workload in performing decision and monitoring tasks by focusing on two mental workload measurements: subjective assessment and time estimation. The task required the assignment of a series of incoming customers to the shortest of three parallel service lines displayed on a computer monitor. The subject was either in charge of the customer assignment (manual mode) or was monitoring an automated system performing the same task (automatic mode). In both cases, the subjects were required to detect the non-optimal assignments that they or the computer had made. Time pressure was manipulated by the experimenter to create fast and slow conditions. The results revealed a multi-dimensional structure of mental workload and a multi-step process of subjective workload assessment. The results also indicated that subjective workload was more influenced by the subject's participatory mode than by the factor of task speed. The time estimation intervals produced while performing the decision and monitoring tasks had significantly greater length and larger variability than those produced while either performing no other tasks or performing a well practised customer assignment task. This result seemed to indicate that time estimation was sensitive to the presence of perceptual/cognitive demands, but not to response related activities to which behavioural automaticity has developed. PMID- 8001526 TI - Eye movement behaviour viewing colour-coded and monochrome avionic displays. AB - This paper reports on two experiments in which subjects' eye movement behaviour was monitored while they searched for target information in colour coded and monochrome horizontal situation indicator (HSI) displays. The first experiment required subjects to locate and report alphanumeric information associated with the active waypoint on the displayed flightpath. Initial fixations in the display were more accurately directed to the target information when it was redundantly colour coded compared with when it was coded by shape and relative positional codes. Fewer fixations and a shorter time were required to locate the colour coded target and verbally report the relevant information. The time advantage of colour coded displays compared with monochrome displays was greatest for visually cluttered displays. In the second study there was no advantage of a coloured display when the task was to count all the displayed waypoint symbols on the flight path. The lack of any benefit for colour coding was a result of waypoint symbols having strong positional predictability due to their relationship to the displayed flightpath in both the colour and monochrome displays. The implication from these results is that colour coded information confers an advantage over a spatial code for targets at unknown spatial location but less benefit when target location can be predicted by other visual cues. PMID- 8001524 TI - Lack of association between vitamin A status and measures of conjunctival epithelial integrity in young children in northern Ghana. AB - OBJECTIVE: To investigate the association between vitamin A status and conjunctival epithelial function in young children in rural northern Ghana and to consider whether impaired epithelial function was associated with increased measures of systemic infection in these children. DESIGN: Children were selected from the Ghana Vitamin A Supplementation Trials' Child Health Study, a randomized, double-blind, placebo-controlled trial of the effect of vitamin A supplementation on morbidity. Treatment group and serum retinol concentrations were used as measures of vitamin A status, conjunctival impression cytology and tear IgA concentrations as measures of conjunctival epithelial integrity, and serum immunoglobulin and alpha 1-acid glycoprotein concentrations as indicators of chronic or acute systemic infection. SUBJECTS: Children 13-64 months old. INTERVENTION: 60 mg retinol as retinyl palmitate every 4 months for 1 year. RESULTS: Vitamin A status was not significantly associated with epithelial integrity nor with measures of systemic infection. Impaired conjunctival epithelial integrity was also not associated with increased systemic infection. CONCLUSIONS: There was no evidence for a major role of improved epithelial integrity and function on the biochemical indices of chronic or acute systemic infection after vitamin A supplementation. These data support the observations in the main study that vitamin A supplementation did not improve conjunctival impression cytology nor decrease the prevalence of most morbidity symptoms. PMID- 8001527 TI - Assessment of cardiac output from noninvasive determination of arterial pressure profile in subjects at rest. AB - The stroke volume of the left ventricle (SV) was calculated from noninvasive recordings of the arterial pressure using a finger photoplethysmograph and compared to the values obtained by pulsed Doppler echocardiography (PDE). A group of 19 healthy men and 12 women [mean ages: 20.8 (SD 1.6) and 22.2 (SD 1.6) years respectively] were studied at rest in the supine position. The ratio of the area below the ejection phase of the arterial pressure wave (A(s)) to SV, as obtained by PDE, yielded a "calibration factor" dimensionally equal to the hydraulic impedance of the system (Zao = A(s).SV-1). The Zao amounted on average to 0.062 (SD 0.018) mmHg.s.cm-3 for the men and to 0.104 (SD 0.024) mmHg.s.cm-3 for the women. The Zao was also estimated from the equation: Zao = a.(d + b.HR + c.PP + e.MAP)-1, where HR was the heart rate, PP the pulse pressure, MAP the mean arterial pressure and the coefficients of the equation were obtained by an iterating statistical package. The value of Zao thus obtained allowed the calculation of SV from measurements derived from the photoplethysmograph only. The mean percentage error between the SV thus obtained and those experimentally determined by PDE amounted to 14.8 and 15.6 for the men and the women, respectively. The error of the estimate was reduced to 12.3 and to 11.1, respectively, if the factor Zao, experimentally obtained from a given heart beat, was subsequently applied to other beats to obtain SV from the A(s) measurement in the same subject. PMID- 8001528 TI - Effect of muscle mass on lactate formation during exercise in humans. AB - To elucidate the mechanisms of lactate formation during submaximal exercise, eight men were studied during one- (1-LE) and two-leg (2-LE) exercise (approximately 11-min cycling) using the catheterization technique and muscle biopsies (quadriceps femoris muscle). The absolute exercise intensity and thus the energy demand for the exercising limb was the same [mean 114 (SEM 7) W] during both 1-LE and 2-LE. At the end of exercise partial pressure of O2 and O2 saturation in femoral venous blood were lower and arterial adrenaline and noradrenaline were higher during 2-LE than during 1-LE. Mean arterial blood lactate concentration increased to 10.8 (SEM 0.8) (2-LE) and 5.2 (SEM 0.4) mmol.l 1 (1-LE) after 10 min of exercise. The intramuscular metabolic response to exercise was attenuated during 1-LE [mean, lactate = 49 (SEM 9); glucose 6-P = 3.3 (SEM 0.3); nicotinamide adenine dinucleotide, reduced = 0.17 (SEM 0.02); adenosine 5'-diphosphate 2.7 (SEM 0.1) mmol.kg dry mass-1] compared to 2-LE [76 (SEM 6); 6.1 (SEM 0.7); 0.21 (SEM 0.02); 3.0 (SEM 0.1) mmol.kg dry mass-1, respectively]. To elucidate whether the lower plasma adrenaline concentration could contribute to the attenuated metabolic response, additional experiments were performed on four of the eight subjects with infusion of adrenaline during 1 LE (1-LEE). Average plasma adrenaline concentration was increased during 1-LEE and reached 2-4 times higher levels than during 2-LE. Post-exercise muscle lactate and glucose 6-P contents were higher during 1-LEE than during 1-LE and were similar to those during 2-LE.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8001529 TI - A method for determining the maximal steady state of blood lactate concentration from two levels of submaximal exercise. AB - The aim of this study was to estimate the characteristic exercise intensity (WCL) which produces the maximal steady state of blood lactate concentration (MLSS) from submaximal intensities of 20 min carried out on the same day and separated by 40 min. Ten fit male adults [maximal oxygen uptake (VO2max) 62 (SD 7) ml.min 1.kg-1] exercised for two 30-min periods on a cycle ergometer at 67% (test 1.1) and 82% of VO2max (test 1.2) separated by 40 min. They exercised 4 days later for 30 min at 82% of VO2max without prior exercise (test 2). Blood lactate was collected for determination of lactic acid concentration every 5 min and heart rate and O2 uptake (VO2) were measured every 30 s. There were no significant differences at the 5th, 10th, 15th, 20th, 25th, or 30th min between VO2, lactacidaemia, and heart rate during tests 1.2 and 2. Moreover, we compared the exercise intensities (WCL) which produced the MLSS obtained during tests 1.1 and 1.2 or during tests 1.1 and 2 calculated from differential values of lactic acid blood concentration ([la-]b) between the 30th and the 5th min or between the 20th and the 5th min. There was no significant difference between the different values of WCL [68 (SD 9), 71 (SD 7, 73 (SD 6), 71 (SD 11)% of VO2max] (ANOVA test, P < 0.05). Four subjects ran for 60 min at their WCL determined from periods performed on the same day (test 1.1 and 1.2) and the difference between the [la ]b at 5 min and at 20 min (delta ([la-]b)) was computed.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8001530 TI - Body mass, body composition and sleeping metabolic rate before, during and after endurance training. AB - Metabolic rate, more specifically resting metabolic rate (RMR) or sleeping metabolic rate (SMR), of an adult subject is usually expressed as a function of the fat-free mass (FFM). Chronic exercise is thought to increase FFM and thus to increase RMR and SMR. We determined body mass (BM), body composition, and SMR before, during, and after an endurance training programme without interfering with energy intake. The subjects were 11 women and 12 men, aged 37 (SD 3) years and body mass index 22.3 (SD 1.5) kg.m-2. The endurance training prepared subjects to run a half marathon competition after 44 weeks. The SMR was measured overnight in a respiration chamber. Body composition was measured by hydrostatic weighing. Measurements were performed at 0, 8, 20, 40, and 90 weeks after the start of the training. The BM had decreased from a mean value of 66.6 (SD 6.9) to 65.6 (SD 6.7) kg (P < 0.01), fat mass (FM) had decreased from 17.1 (SD 3.9) to 13.5 (SD 3.6) kg (P < 0.001), and FFM had increased from 49.5 (SD 7.3) to 52.2 (SD 7.6) kg (P < 0.001) at 40 weeks. Mean SMR before and after 40 weeks training was 6.5 (SD 0.7) and 6.2 (SD 0.6) MJ.day-1 (P < 0.05). The decrease in SMR was related to the decrease in BM (r = 0.62, P = 0.001). At 90 weeks, when most subjects had not trained for nearly a year, BM and SMR were not significantly different from the initial value while FM and FFM had not changed since week 40 of training.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8001532 TI - Cold thermoregulatory changes induced by sleep deprivation in men. AB - The aim of this study was to evaluate the thermoregulatory changes induced by 27 h of sleep deprivation (SD) in men at rest both in a comfortable ambient temperature and in cold air. A group of 12 male subjects were placed in a comfortable ambient temperature (dry bulb temperature, Tdb = 25 degrees C, relative humidity, rh = 40%-50%, clothing insulation = 1 clo) for 1 h and then they were submitted to a standard cold air test in a climatic chamber for 2 h (Tdb = 1 degree C, rh = 40%-50%, wind speed = 0.8 m.s-1, nude), before and after 27 h of sleep deprivation. Thermoregulatory changes (rectal temperature, Tre; mean skin temperature. Tsk; metabolic heat production M) were monitored continuously. At comfortable ambient temperature, no significant change was observed after SD for Tre, Tsk and M. During the cold test, Tre did not change but Tsk and M were higher after SD (P < 0.05). Increased M (+ 6%, P < 0.05) was related to earlier and higher shivering, with a possible increase in the sensitivity of the thermoregulatory system as shown by the shorter time to onset of continuous shivering (d): 8.66 (SEM 1.33) min versus 28.20 (SEM 1.33) min (P < 0.001) and by a higher Tsk observed at d: 27.60 (SEM 1.40) degrees C versus 21.40 (SEM 0.60) degrees C (P < 0.001). These results were associated with higher cold sensations and shivering following SD. They also suggested that SD modified thermoregulatory responses at a central level especially in a cold environment. PMID- 8001531 TI - Post-exercise rehydration in man: effects of electrolyte addition to ingested fluids. AB - This study examined the effects on water balance of adding electrolytes to fluids ingested after exercise-induced dehydration. Eight healthy male volunteers were dehydrated by approximately 2% of body mass by intermittent cycle exercise. Over a 30-min period after exercise, subjects ingested one of the four test drinks of a volume equivalent to their body mass loss. Drink A was a 90 mmol.l-1 glucose solution; drink B contained 60 mmol.l-1 sodium chloride; drink C contained 25 mmol.l-1 potassium chloride; drink D contained 90 mmol.l-1 glucose, 60 mmol.l-1 sodium chloride and 25 mmol.l-1 potassium chloride. Treatment order was randomised. Blood and urine samples were obtained at intervals throughout the study; subjects remained fasted throughout. Plasma volume increased to the same extent after the rehydration period on all treatments. Serum electrolyte (Na+, K+ and Cl-) concentrations fell initially after rehydration before returning to their pre-exercise levels. Cumulative urine output was greater after ingestion of drink A than after ingestion of any of the other drinks. On the morning following the trial, subjects were in greater net negative fluid balance [mean (SEM); P < 0.02] on trial A [745 (130) ml] than on trials B [405 (51) ml], C [467 (87) ml] or D [407 (34) ml]. There were no differences at any time between the three electrolyte-containing solutions in urine output or net fluid balance. One hour after the end of the rehydration period, urine osmolality had fallen, with a significant treatment effect (P = 0.016); urine osmolality was lowest after ingestion of drink A.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8001533 TI - Physiological changes induced by pre-adaptation to high altitude. AB - To study the physiological effects of pre-adaptation to high altitude, seven subjects were submitted to acclimatization at 4350 m followed by intermittent acclimation in a low barometric pressure chamber (5000 m to 8500 m). The subjects then spent 25 days in the Himalayas. Ventilatory and cardiac responses were studied during a hypobaric poikilocapnic hypoxic test performed both at rest and during exercise (100 W) in normoxia and in hypoxia (barometric pressure: 589 hPa, altitude: 4500 m). Haemoglobin, erythrocytes, reticulocytes, packed cell volume, 2,3-diphosphoglycerate (2,3-DPG) and erythropoietin (EPO) were measured. All variables were studied before pre-adaptation to high altitude (A), after the acclimatization period (B), after the acclimation period (C) and after the expedition (D). The ventilatory and cardiac responses were characterized by an increased tidal volume in hypoxia (+33% during exercise in B, P < 0.05; +100% at rest and +33% during exercise in C, P < 0.05) without any change in respiratory frequency, whereas an increased systolic blood pressure was only observed in C during exercise in hypoxia [+23 mmHg (3.07 kPa), P < 0.01]. Arterial O2 saturation was higher in hypoxia in C and D, both at rest (+8.2% and +4.7%, P < 0.01, respectively), and during exercise (+6.3% and +6.3%, P < 0.01, respectively). Erythrocytes, haemoglobin and packed cell volume did not vary significantly. The number of reticulocytes was higher in B (+172%, P < 0.05) and in C (+249%, P < 0.05). EPO and 2,3-DPG increased only in C (+770%, P < 0.01 and +23%, P < 0.05, respectively).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8001534 TI - Mechanisms of potentiation in sweating induced by long-term physical training. AB - To evaluate the mechanism of potentiation of sweating after long-term physical training, we compared sweating function in trained and untrained subjects using the frequency of sweat expulsion (fsw) as an indicator of central sudomotor activity. Nine trained male subjects (trained group) and eight untrained male subjects (untrained group) performed 30-min cycle exercise at 35% maximal oxygen uptake at 25 degrees C ambient temperature and 35% relative humidity. Oesophageal temperature (T(oes)), mean body temperature (Tb), chest sweating rate (msw,chest), forearm sweating rate (msw,forearm), and fsw were measured. The slopes of the msw,chest versus body temperature (T(oes) and Tb) and versus fsw relationships in the trained group were significantly greater than those in the untrained group (both, P < 0.05), while there was no difference between the groups in the slopes of the msw,forearm versus body temperature or versus fsw relationships. Neither the body temperature threshold for initiation of chest or forearm sweating nor the slope of the fsw-Tb relationship differed between groups. We concluded that, during light exercise at moderate ambient temperature, the msw,chest in the subjects who had undergone long-term physical training was greater than that in the untrained subjects while the msw,forearm was not changed. The greater msw,chest in the trained subjects was concluded to be due to an increase of sensitivity of peripheral mechanisms. PMID- 8001536 TI - Maximal isometric force and neural activity during bilateral and unilateral elbow flexion in humans. AB - We investigated maximal isometric force and electromyographic (EMG) activity of the biceps brachii muscle during rapid bilateral (BL) and unilateral (UL) elbow flexion in 11 right-handed subjects. The BL exhibited a deficit in force for both arms and more so for the right than the left arm during the rising phase of force generation. The EMG of the left biceps brachii muscle was similar during UL and BL, but for the right arm EMG was lower during BL than during UL for the rising phase of force generation. The BL to UL ratio of mean power frequency of the EMG was lower for the right than for the left arm. The data would suggest that the relatively small BL strength was associated with a equally small EMG and a shift to a lower mean power frequency especially for the fast motor units of the dominant muscle. PMID- 8001535 TI - Neuromuscular performance of lower limbs during voluntary and reflex activity in power- and endurance-trained athletes. AB - Neural, mechanical and muscle factors influence muscle force production. This study was therefore, designed to compare possible differences in the function of the neuromuscular system among differently adapted subjects. A group of 11 power trained athletes and 10 endurance-trained athletes volunteered as subjects for this study. Maximal voluntary isometric force and the rate of force production of the knee extensor and the plantar flexor muscles were measured. In addition, basic reflex function was measured in the two experimental conditions. The power athletes produced higher voluntary forces (P < 0.01-0.001) with higher rates for force production (P < 0.001) by both muscle groups measured. Unexpectedly, however, no differences were noticed in the electromyogram time curves between the groups. During reflex activity, the endurance group demonstrated higher sensitivity to the mechanical stimuli, i.e. the higher reflex amplitude caused a higher rate of reflex force development, and the reflex amplitude correlated with the averaged angular velocity. The differences in the isometric conditions could be explained by obviously different muscle fibre distribution, by different amounts of muscle mass, by possible differences in the force transmission from individual myofibrils to the skeletal muscle and by specificity of training. In addition, differences in nervous system structure and muscle spindle properties could explain the observed differences in reflex activity between the two groups. PMID- 8001537 TI - Noninvasive assessment of cardiac contractility by using (dP/dt)/P of carotid artery pulses during exercise. AB - In earlier studies we have shown that both the pressure (P) of the carotid artery pulse (CAP) and its first derivative (CAP dP/dt) could be recorded during moderate exercise. To establish that the CAP (dP/dt)/P is a noninvasive substitute for the left ventricular (LV) value, LV (dP/dt)/P, an index of cardiac contractility, we studied CAP (dP/dt)/P under various states of activity in the autonomic nervous system in 12 healthy male subjects. Increased sympathetic nerve activities yielded by passive tilting, emotional load, or cold stress increased CAP (dP/dt)/P significantly (P < 0.05). Increased parasympathetic nerve activity by ocular compression, however, did not significantly affect the value. Moderate exercise at a heart rate of approximately 150 beats.min-1 increased it significantly from 16.7 to 25.2.s-1 in a supine position (P < 0.001) and from 16.6 to 24.8.s-1 in an upright position (P < 0.001). It increased monotonically as heart rate increased, but the slope was steeper when the heart rate was greater than approximately 100 beats.min-1 than it was when the rate was less than 100 beats.min-1. In conclusion, the present study indicated that CAP (dP/dt)/P can be used as a noninvasive index of cardiac contractility even in moderate exercise. PMID- 8001538 TI - Use of the iso-inertial force mass relationship in the prediction of dynamic human performance. AB - The purpose of this investigation was to develop a new test of muscle function, termed the iso-inertial force-mass relationship, and to determine its relationship to dynamic physical performance in comparison to an isometric test. A group of 13 trained subjects performed an isometric, and a series of iso inertial maximal upper body tests, in a bench press movement at loads of 30%, 60%, 100% (concentric) and 100%, 130% and 150% (eccentric) of maximum. Vertical forces exerted throughout the movement were recorded by a force plate. In addition, the subjects performed the following three performance tests: a maximal bench press, a seated shotput, and two drop bench-press throws from a height of 0.25 m, with loads of 10 kg and 30% of maximum. Correlation analysis demonstrated that in each instance the iso-inertial force mass tests were the best predictors of performance (r = 0.78-0.88) with both contraction type and mass specific effects apparent. Maximal isometric force and rate of force development were significantly related to some performance variables (r = 0.22-0.78). However, for all the performance movements assessed, the iso-inertial test modality recorded the highest relationship to performance. The difference in the relationship between performance and iso-inertial and isometric test modalities was particularly evident in the light load dynamic performance of the seated shotput (r = 0.86 vs r = 0.38, respectively). These results are explained in part by the neural and mechanical differences between iso-inertial and isometric muscle actions and their respective specificity to dynamic physical performance. PMID- 8001539 TI - Use of oxygen uptake recovery curve to predict peak oxygen uptake in upper body exercise. AB - A group of 18 well-trained white-water kayakers performed maximal upper body exercise in the laboratory and during a field test. Laboratory direct peak oxygen uptake (VO2) values were compared, firstly by a VO2 backward extrapolation estimation and secondly by an estimation calculated from VO2 measured during the first 20 s of exercise recovery. Direct peak VO2 correlated with VO2 backward extrapolation (r = 0.89), but the results of this study showed that the backward extrapolation method tended to overestimate significantly peak VO2 by [0.57 (SD 0.31) l.min-1 in the laboratory, and 0.66 (SD 0.33) l.min-1 in the field, P < 0.001]. The VO2 measured during the first 20 s of recovery, whether the exercise was performed in the laboratory or in the field, correlated well with the laboratory direct peak VO2 (r = 0.92 and r = 0.91, respectively). The use of the regression equation obtained from field data (VO2F20s), that is peak VO2 = 0.23 + 1.08 VO2F20s, gave an estimated peak VO2, the mean difference of which compared with direct peak VO2 was 0.22 (SD 0.13) l.min-1. In conclusion, we propose the use of a regression equation to estimate peak VO2 from a single sample of the gas expired during the first 20 s of recovery after maximal exercise involving the upper part of the body. PMID- 8001540 TI - Imposed breathing pattern alters respiratory work during exercise. AB - Previous studies have shown the existence of an ideal respiratory rate (fR) for a given ventilation at which the respiratory work rate (J.s-1) is minimum. The purpose of the present study was to measure the effect of fR, tidal volume and breathing pattern on the respiratory work per breath and respiratory work rate during exercise on a cycle ergometer. Three work rates on the cycle ergometer were used and at each work rate the ventilation was kept constant. Two different breathing patterns were applied at each ventilation. Nine male trained cyclists [mean (SD) maximum oxygen consumption, 57 (5.47) ml.kg-1.min-1] participated in this study. The results indicated that there was a significant difference in the respiratory work per breath, with different breathing patterns at a given ventilation and for all levels of ventilation. There was no significant difference in the respiratory work rate with different breathing patterns at a given ventilation and for all levels of ventilation. In addition, the respiratory work per breath and respiratory work rate were increased with increasing ventilation. Thus, the data indicated that the manipulation of tidal volume, respiratory rate and breathing pattern had no significant effect on the energy cost of breathing for a given ventilation. The absence of this significant effect on respiratory work rate was observed across a range of ventilation from 24 to 72 l.min-1. These findings suggest that the breathing pattern is predominantly an expression of the function of the higher respiratory brain center instead of energy economy, at least within this range of ventilation. PMID- 8001541 TI - The influence of dietary creatine supplementation on performance during repeated bouts of maximal isokinetic cycling in man. AB - The effect of dietary creatine (Cr) supplementation on performance during 3, 30 s bouts maximal isokinetic cycling and on plasma ammonia and blood lactate accumulation during exercise was investigated. Placebo (P) ingestion had no effect on peak power output (PPO), mean power output (MPO) and total work output during each bout of exercise. Cr ingestion (4 x 5 g.day-1 for 5 days) significantly increased PPO in exercise bout 1 (p < 0.05) and MPO and total work output in exercise bouts 1 (p < 0.05, p < 0.05, respectively) and 2 (p < 0.05, p < 0.05, respectively). Cr ingestion had no effect on any of the measures of performance during exercise bout 3. No difference was observed in peak plasma ammonia accumulation before (146 + 30 mumol.l-1) and after (122 +/- 17 mumol.l-1) P ingestion, however the corresponding concentration was lower following Cr ingestion (129 +/- 22 mumol.l-1) compared with before Cr ingestion (160 +/- 18 mumol.l-1, p < 0.05), despite subjects performing more work. No difference in peak blood lactate accumulation was observed before and after P or Cr ingestion. The results demonstrate that Cr ingestion can increase whole body exercise performance during the initial two, but not a third, successive bout of maximal exercise lasting 30 s. The lower accumulation of plasma ammonia under these conditions suggests this response is achieved by an effect on muscle ATP turnover. PMID- 8001542 TI - Times to exhaustion at 100% of velocity at VO2max and modelling of the time limit/velocity relationship in elite long-distance runners. AB - The aim of this study was to measure running times to exhaustion (Tlim) on a treadmill at 100% of the minimum velocity which elicits VO2max (vVO2max in 38 elite male long-distance runners (VO2max = 71.4 +/- 5.5 ml.kg-1.min-1 and vVO2max = 21.8 +/- 1.2 km.h-1). The lactate threshold (LT) was defined as a starting point of accelerated lactate accumulation around 4 mM and was expressed in %VO2max. Tlim value was negatively correlated with vVO2max (r = -0.362, p < 0.05) and VO2max (r = -0.347, p < 0.05) but positively with LT (% vVO2max) (r = 0.378, p < 0.05). These data demonstrate that running time to exhaustion at vVO2max in a homogeneous group of elite male long-distance runners was inversely related to vVO2max and experimentally illustrates the model of Monod and Scherrer regarding the time limit-velocity relationship adapted from local exercise for running by Hughson et al. (1984). PMID- 8001543 TI - An evaluation of receptor-mediated gene transfer using synthetic DNA-ligand complexes. AB - Receptor-mediated gene transfer is an attractive method for therapeutically correcting human genetic diseases since it permits the targeting of DNA to cellular receptors in specific tissues of adult animals. Genes introduced by this technique have been shown to be expressed in the target tissue for varying periods. However, to be useful for gene therapy, it is critical that both the chemical properties and physical interactions of the reagents involved in the design of the DNA delivery vehicle be rigorously characterized. In this review, we discuss the critical steps in the preparation of the DNA-ligand complex and the factors involved in the delivery and regulated expression of a transgene in animal tissues. The feasibility of using this technique for the therapeutic delivery of genes to mammalian tissues will also be evaluated. PMID- 8001544 TI - Activation of a GTP-binding protein and a GTP-binding-protein-coupled receptor kinase (beta-adrenergic-receptor kinase-1) by a muscarinic receptor m2 mutant lacking phosphorylation sites. AB - A mutant of the human muscarinic acetylcholine receptor m2 subtype (m2 receptor), lacking a large part of the third intracellular loop, was expressed and purified using the baculovirus/insect cell culture system. The mutant was not phosphorylated by beta-adrenergic-receptor kinase, as expected from the previous assignment of phosphorylation sites to the central part of the third intracellular loop. However, the m2 receptor mutant was capable of stimulating beta-adrenergic-receptor-kinase-1-mediated phosphorylation of a glutathione S transferase fusion protein containing the m2 phosphorylation sites in an agonist dependent manner. Both mutant and wild-type m2 receptors reconstituted with the guanine-nucleotide-binding regulatory proteins (G protein), G(o) and G(i)2, displayed guanine-nucleotide-sensitive high-affinity agonist binding, as assessed by displacement of [3H]quinuclidinyl-benzilate binding with carbamoylcholine, and both stimulated guanosine 5'-3-O-[35S]thiotriphosphate ([35S]GTP[S]) binding in the presence of carbamoylcholine and GDP. The Ki values of carbamoylcholine effects on [3H]quinuclidinyl-benzilate binding were indistinguishable for the mutant and wild-type m2 receptors. Moreover, the phosphorylation of the wild-type m2 receptor by beta-adrenergic-receptor kinase-1 did not affect m2 interaction with G proteins as assessed by the binding of [3H]quinuclidinyl benzilate or [35S]GTP[S]. These results indicate that (a) the m2 receptor serves both as an activator and as a substrate of beta-adrenergic-receptor kinase, and (b) a large part of the third intracellular loop of the m2 receptor does not contribute to interaction with G proteins and its phosphorylation by beta-adrenergic-receptor kinase does not uncouple the receptor and G proteins in reconstituted lipid vesicles. PMID- 8001545 TI - Multiple proline substitutions cumulatively thermostabilize Bacillus cereus ATCC7064 oligo-1,6-glucosidase. Irrefragable proof supporting the proline rule. AB - Nine residues of Bacillus cereus ATCC7064 oligo-1,6-glucosidase were replaced stepwise with proline residues. Of the nine residues, Lys121, Glu208 and Glu290 were at second sites of beta turns; Asn109, Glu175 and Thr261 were at N-caps of alpha helices; Glu216, Glu270 and Glu378 were in coils within loops. The replacements were carried out in the order, Lys121-->Pro, Glu175-->Pro, Glu290- >Pro, Glu208-->Pro, Glu270-->Pro, Glu378-->Pro, Thr261-->Pro, Glu216-->Pro and Asn109-->Pro. The resultant nine active mutant enzymes contained 1-9 more proline residues than B. cereus oligo-1,6-glucosidase. The thermostability of these mutants was additively enhanced with the increase in the number of proline residues introduced. The increase in the thermostability was most remarkable when proline residues were introduced at second sites of beta turns or at N-caps of alpha helices. The above results afforded irrefragable proof for the proline rule as an effective principle for increasing protein thermostability [Suzuki, Y., Oishi, K., Nakano, H. & Nagayama, T. (1987) Appl. Microbiol. Biotechnol. 26, 546 551]. PMID- 8001546 TI - Purification and characterization of a rhamnogalacturonase with protopectinase activity from Trametes sanguinea. AB - In a culture filtrate of Trametes sanguinea IFO 6490, we found a protopectin solubilizing enzyme, protopectinase-T, that did not degrade polygalacturonic acid. The enzyme was purified to homogeneity with hydrophobic, cation-exchange, anion-exchange, and size-exclusion chromatographies. It had an apparent molecular mass of 55 kDa by SDS/PAGE and 39 kDa by size-exclusion chromatography on Superose 12. The isoelectric point was at pH 8.1. Protopectinase-T was stable from pH 3.0 to 6.0 and at temperatures up to 50 degrees C. The optimum pH for enzyme activity was 4.0 at 37 degrees C, and the optimum temperature was 50 degrees C at pH 5.0. Protopectinase-T catalyzed the release of highly polymerized pectin from lemon peel protopectin. PMID- 8001547 TI - De novo sulfation of L-tyrosine in HepG2 human hepatoma cells and its possible functional implication. AB - HepG2 human hepatoma cells, labeled with [35S]sulfate in the presence of 10-30 micrograms/ml of cycloheximide, released up to 64% of the amount of free tyrosine O-[35S]sulfate produced and released by cells labeled in the absence of cycloheximide. A time-course study revealed that, in cells incubated in medium containing [3H]tyrosine, free [3H]tyrosine-O-sulfate was produced within 5 min of incubation, whereas no [3H]tyrosine-sulfated proteins were detected until 20 min after the incubation had begun. Using 3'-phosphoadenosine, 5'-phospho[35S]sulfate as the sulfate donor, HepG2 cell homogenate was shown to contain enzymic activity catalyzing the sulfation of L-tyrosine with the formation of tyrosine-O [35S]sulfate. Upon subcellular fractionation, the majority of the enzyme activity was found in the cytosolic fraction. The enzyme, designated tyrosine sulfotransferase, displayed the optimum activity at pH 8.0 in the presence of 10 mM Mn2+. Under optimum conditions, the apparent Km of the enzyme for L-tyrosine, at 4.5-microM concentration of 3'-phosphoadenosine, 5'-phosphosulfate, was determined to be 1.95 mM, while that for 3'-phosphoadenosine, 5'-phosphosulfate, at 1 mM L-tyrosine concentration, was 8.3 microM. The Vmax determined under these conditions was 1.05 pmol.min-1.mg protein-1. A tyrosine-dependence study showed that, for cells labeled with [35S]sulfate, the production and release of free tyrosine-O-[35S]sulfate appeared to proceed actively and increase proportionally to the L-tyrosine concentration when it was raised above a threshold level in the culture medium. These results may imply a possible involvement of sulfation in removing excess intracellular L-tyrosine. PMID- 8001548 TI - Identification and partial purification of calmodulin-binding microtubule associated proteins from Neurospora crassa. AB - We have purified microtubule-associated proteins from Neurospora crassa on the basis of heat stability and affinity to calmodulin. Two proteins of molecular masses 170 kDa and 190 kDa have been partially purified. A third protein of 145 kDa was purified almost to homogeneity, and we present evidence that this protein is a specific substrate for a Ca2+/calmodulin-dependent protein kinase. The purified 170-, 190-, and 145-kDa proteins induce the assembly of microtubules from purified porcine brain tubulin. We demonstrate that all three proteins are microtubule-associated proteins on the basis of an in vitro microtubule-binding assay. PMID- 8001549 TI - Cathepsin B, a cysteine protease implicated in metastatic progression, is also expressed during regression of the rat prostate and mammary glands. AB - We have developed a novel library-to-library cross-screening technology to clone unique mRNAs that are expressed during tissue regression. We have cloned a number of regression selected genes (RSG) that are expressed during the regression of the mammary gland and ventral prostate of the rat after the removal of the respective trophic hormone. In this investigation, we have characterized one of these genes, RSG-2, that is homologous to cathepsin B, a thiol protease that has been previously identified as one of the extracellular proteases which is activated in metastatic cells. The steady-state levels of RSG-2 mRNA in the normal prostate are low but detectable. In the regressing prostate, RSG-2 mRNA levels peak at 3-4 days after castration, at the time that tissue regression is maximal. The gene is induced in a similar fashion in the regressing mammary gland. Using in situ hybridization, we have established that RSG-2 mRNA is expressed in the luminal epithelial cells of the prostate and mammary gland that are known to undergo active cell death, suggesting that it may be a general marker for secretory epithelial cell death. Analysis of the distribution of the cathepsin B protein by immunofluorescence microscopy demonstrates that there is diffuse, but punctate, expression of the protein in all of the luminal epithelial cells of the normal prostate and mammary gland. However, at early times after hormone ablation in both glands, the majority of the increase in cathepsin B protein appears to result from redistribution to the basal aspect of the cells. At later time points, there appears to be increased amounts of the protein which is localized to the apoptotic bodies. These results suggest that RSG-2, or cathepsin B, is required for the local degradation of the basement membrane, which is one of the earliest morphologically recognizable events of active cell death. PMID- 8001550 TI - Probing the structure of hirudin from Hirudinaria manillensis by limited proteolysis. Isolation, characterization and thrombin-inhibitory properties of N terminal fragments. AB - Hirudin is the most potent and specific inhibitor of the blood-clotting enzyme thrombin so far known. Several hirudin variants were isolated mostly from Hirudo medicinalis and shown to be polypeptide chains of approximately 7 kDa with three internal disulfide bridges. In this study, limited proteolysis has been used to probe aspects of the structure and dynamics of a hirudin variant HM2 isolated from Hirudinaria manillensis. Proteolysis of the polypeptide chain of 64-amino acid residues of hirudin HM2 by protease from Staphylococcus aureus V8, trypsin, thermolysin and subtilisin occurs at region 41-49 of the chain. The N-terminal fragments 1-41 and 1-47 were isolated to homogeneity and shown to maintain inhibitory action on thrombin, though much lower than the intact protein. The results were interpreted on the basis of a proposed three-dimensional structure of hirudin HM2 deduced by protein modelling the known structure of hirudin variant HV1 from Hirudo medicinalis (75% sequence similarity between HM2 and HV1). Both proteolysis experiments and protein modelling provide evidence for the existence in hirudin HM2 of a N-terminal well-structured domain (core) and a C terminal flexible polypeptide segment. Determination of the accessible surface area of the three-dimensional model of hirudin HM2 showed that the sites of preferential cleavages are at the surface of the polypeptide molecule. PMID- 8001551 TI - C-terminal proteolytic degradation of recombinant desulfato-hirudin and its mutants in the yeast Saccharomyces cerevisiae. AB - The potent thrombin inhibitor hirudin variant 1, originally isolated from the leech Hirudo medicinalis, was expressed in Saccharomyces cerevisiae under the control of a truncated glyceraldehyde-3-phosphate dehydrogenase (GAP) promoter fragment. Fusion of the yeast acid phosphatase (PHO5) signal sequence to the hirudin gene led to quantitative secretion of recombinant desulfato-hirudin variant 1 (r-hirudin) into the extracellular medium in a growth-dependent manner. In comparison to the genuine molecule, r-hirudin lacks the sulfate group at the Tyr in position 63. Besides the full-length protein of 65 amino acids (hir65), chemical analysis revealed the presence mainly of two derivatives lacking the last amino acid Gln (hir64) or the penultimate Leu (hir63) in addition. When expressing r-hirudin in mutant strains defective in all but one of the three major known carboxypeptidases, it turned out that the vacuolar carboxypeptidase yscY as well as the alpha-factor precursor-processing carboxypeptidase, ysc alpha, participate in the C-terminal degradation of r-hirudin. Direct involvement of yscY and ysc alpha was confirmed by sequential disruption of their structural genes PRC1 and KEX1, respectively. Disruption of PRA1, coding for the yscY processing proteinase yscA, also abolished yscY-mediated C-terminal r-hirudin degradation, but clearly reduced the overall expression yield. Since ysc alpha is described to be highly specific for basic amino acids which are not present at the C-terminus of r-hirudin, a series of r-hirudin mutants with changes in the C terminal amino acids were constructed and analysed for ysc alpha-mediated and yscY-mediated degradation. Chromatographic analysis of the expression products confirmed the preference of ysc alpha for basic amino acids, although Tyr, Leu and Gln were also hydrolysed. It could further be concluded that ysc alpha might also be responsible for the C-terminal degradation of recombinant atrial natriuretic factor and epidermal growth factor expressed in yeast. PMID- 8001552 TI - Dissociation rate of cognate peptidyl-tRNA from the A-site of hyper-accurate and error-prone ribosomes. AB - The binding stability of the aminoacyl-tRNA site (A-site), estimated from the dissociation rate constant kd, of AcPhe-Phe-tRNA(Phe) has been studied for wild type (wt), for hyperaccurate ribosomes altered in S12 [streptomycin-dependent (SmD) and streptomycin-pseudodependent (SmP) phenotypes], for error-prone ribosomes altered in S4 (Ram phenotype), and for ribosomes in complex with the error-inducing aminoglycosides streptomycin and neomycin. The AcPhe2-tRNA stability is slightly and identically reduced for SmD and SmP phenotypes in relation to wt ribosomes. The stability is increased (kd is reduced) for Ram ribosomes to about the same extent as the proof-reading accuracy is decreased for this phenotype. kd is also reduced by the action of streptomycin and neomycin, but much less than the reduction in proof-reading accuracy induced by streptomycin. Similar kd values for SmD and SmP ribosomes indicate that the cause of streptomycin dependence is not excessive drop-off of peptidyl-tRNAs from the A site. PMID- 8001554 TI - The amino acid sequence of the red kidney bean Fe(III)-Zn(II) purple acid phosphatase. Determination of the amino acid sequence by a combination of matrix assisted laser desorption/ionization mass spectrometry and automated Edman sequencing. AB - Purple acid phosphatase of the common bean Phaseolus vulgaris is a homodimeric 110-kDa glycoprotein with a Fe(III)-Zn(II) center in the active site of each monomer. After exchange of Zn(II) for Fe(II), the enzyme spectroscopically and kinetically resembles the mammalian purple acid phosphatases with Fe(III)-Fe(II) centers in monomeric 35-kDa proteins. The kidney bean enzyme consists of 432 amino acids/monomer with five N-glycosylated asparagine residues. The complete amino acid sequence was determined by a combination of matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS) and classical sequencing methods. Our strategy involved mass determination and sequence analysis of all cyanogen-bromide-generated fragments by automated Edman degradation. Limited cleavages with cyanogen bromide were performed to obtain fragments containing still uncleaved Met-Xaa linkages. MALDI mass spectra of these products allowed the characterization of each fragment and the determination of the order of the cyanogen bromide fragments in the intact protein without producing overlapping peptides. For one large 30-kDa methionine-free fragment, the alignment of the Edman-degraded tryptic peptides was obtained by MALDI-MS analysis and enzymic microscale peptide laddering of overlapping Glu-C-generated fragments. The employed strategy shows that the classical method, in combination with modern mass spectrometry, is an attractive approach for primary structure determination in addition to the DNA sequencing method. PMID- 8001553 TI - In vitro proteolytic activity and active-site identification of the human cytomegalovirus protease. AB - Human cytomegalovirus (HCMV) encodes a protease that cleaves itself and the HCMV assembly protein. Two proteolytic processing sites within the protease were identified at Ala 256-Ser 257 (release site) and Ala 643-Ser 644 (maturation site). Identification of rP5-P4' and mP4-P6' as the minimal peptide substrates spanning the release and maturation cleavage sites, respectively, demonstrated a requirement for residues flanking the conserved core in substrate recognition and hydrolysis, which are unique to HCMV. Kinetic parameters determined for release site-derived and maturation-site-derived peptides revealed a 10-fold increase in kcat/Km for a maturational peptide (mP4-P8') over release-site peptide (rP5-P5'). Experimental results with a panel of class-specific protease inhibitors were consistent with the protease being a member of the serine or cysteine family of proteases. Further investigation revealed that the HCMV protease activity decreased with incorporation of [14C]iodoacetic acid, but when approximately 4.5 mol 14C were incorporated/mol enzyme, the enzyme retained approximately 20% of its original activity, indicating that hydrolysis does not require a cysteine nucleophile. Analysis of diisopropyl-fluorophosphate-inactivated protease by mass spectrometry indicated a stoichiometry of 1 diisopropyl phosphate/protease molecule, suggesting that hydrolysis requires a single serine nucleophile. The residue modified by diisopropyl fluorophosphate was identified as Ser132 by modification with 3H-labeled diisopropyl fluorophosphate, peptide mapping and Edman degradation. This residue and the region in which it is found is highly conserved among the herpes virus proteases. These data demonstrates that HCMV protease is a serine protease and that Ser132 is the active-site nucleophile. PMID- 8001555 TI - Promoter function of the human glucose-6-phosphate dehydrogenase gene depends on two GC boxes that are cell specifically controlled. AB - Human glucose-6-phosphate dehydrogenase is expressed in all cells by a housekeeping gene whose regulatory 5'-flanking sequence includes at least nine GC boxes. By transient transfection of HeLa and HepG2 cells with constructs containing glucose-6-phosphate dehydrogenase gene regions linked to a reporter gene, we have now delineated the core promoter and have located upstream stimulatory and inhibitory sequences. By mutational analysis, we demonstrate that the activity of the core promoter requires two out of seven GC boxes. We show that stimulatory protein 1 (Sp1)-related factors and activator protein 2 (AP-2) related proteins bind to these two boxes in band-shift experiments. One point mutation that affects the binding of only the Sp1-related factors to one or both boxes causes a marked decrease of promoter activity in HepG2 cells but not in HeLa cells. We conclude that (a) two out of many seemingly redundant GC boxes are necessary to drive a G+C-rich housekeeping promoter; (b) factors that bind to GC boxes may exert cell-type-specific regulation of housekeeping gene promoter activity; (c) point mutations in the promoter of the glucose-6-phosphate dehydrogenase gene can inhibit its transcription. PMID- 8001556 TI - Correct post-translational modification and stable vacuolar accumulation of phytohemagglutinin engineered to contain multiple methionine residues. AB - Most legume seed storage proteins are deficient in sulfur amino acids. In this study, we demonstrate that replacing specific amino acid residues of a seed protein with methionine residues at positions known to be occupied by methionine residues in homologous proteins, is an effective strategy to create methionine enriched seed proteins. Mutant phytohemagglutinin polypeptides with three or four methionine residues were found to undergo correct post-translational modifications in transformed cultured tobacco cells and to accumulate stably in the protein storage vacuoles of transgenic tobacco seeds. PMID- 8001557 TI - Modulation of activator protein-1 (AP-1) transcription factor and protein kinase C by hydrogen peroxide and D-alpha-tocopherol in vascular smooth muscle cells. AB - The effects of hydrogen peroxide D-alpha-tocopherol and of D-beta-tocopherol on proliferation, protein kinase C and activator protein-1 (AP-1) activation have been studied in vascular smooth muscle cells. Cell proliferation, when activated by foetal calf serum, was inhibited by D-alpha-tocopherol. Protein kinase C activity was stimulated by hydrogen peroxide in a manner similar to phorbol myristate acetate; in the latter case, but not in the former, D-alpha-tocopherol inhibited the reaction. Hydrogen peroxide prevented phorbol-myristate-acetate stimulated AP-1 binding to DNA but stimulated it if protein kinase C was down regulated or inhibited. D-alpha-Tocopherol promoted AP-1 activation in quiescent cells but prevented its activation by phorbol myristate acetate. None of the described effects of D-alpha-tocopherol were shared by D-beta-tocopherol, suggesting a non-antioxidant mechanism as the basis of its action. The data show that hydrogen peroxide and D-alpha-tocopherol affect more than one element in the cell signal-transduction cascade. PMID- 8001558 TI - Purification and biochemical characterization of TrwC, the helicase involved in plasmid R388 conjugal DNA transfer. AB - TrwC is an essential protein in conjugative DNA transfer of the broad-host-range plasmid R388. TrwC was purified in two chromatographic steps from TrwC overproducing bacteria. The purification procedure resulted in > 90% pure TrwC protein, which was free of contaminating nuclease activities. TrwC behaved as a dimer in gel-filtration chromatography in the presence of 550 mM NaCl, and had a pI of 10.1. The purified protein showed in-vitro ssDNA-dependent nucleoside-5' triphosphatase and DNA helicase activities. ATP was the preferred substrate for the NTP hydrolysis reaction, which required Mg2+. The helicase activity was dependent on ATP and Mg2+. The efficiency of the unwinding reaction catalyzed by TrwC ranged from > 90% of fragment displaced for a 93-nucleotide sequence to < 5% for a 365-nucleotide sequence. Unwinding was unidirectional in the 5' to 3' direction. The enzyme turned over very slowly from one DNA substrate molecule to another. TrwC is only the second DNA helicase to be described which is involved in conjugative DNA transfer. The biochemical properties of TrwC described here confirm its functional relatedness to helicase I (TraI) encoded by plasmid F of E. coli. PMID- 8001559 TI - Three-dimensional structure in solution of a wheat lipid-transfer protein from multidimensional 1H-NMR data. A new folding for lipid carriers. AB - Two-dimensional and three-dimensional 1H-NMR experimental data [Simorre, J. P., Caille, A., Marion, D., Marion, D. & Ptak, M. (1991) Biochemistry 30, 11600 11608] were used to build models of the three-dimensional structure of a non specific wheat lipid-transfer protein (LTP) by using distance geometry, simulated annealing, energy minimization and molecular dynamics techniques. A first set of 881 distance constraints derived from NOE cross-peak intensities was used to generate 74 initial structures. One family of topological mirror images of the protein structure was eliminated by considering helical secondary-structure organization and steric requirements. Back calculations of NOE intensities led us to introduce 535 additional distance constraints. Finally, 21 structures were selected as representative of the structure of the protein. The polypeptide backbone folds into a simple and original right-handed winding. It is composed of a bundle of four helices linked by flexible loops, which is packed against a C terminal fragment forming a non-standard saxophone-like shape. The folded protein is stabilized by hydrophobic interactions and the four disulfide bridges combined by pairs on each side of the protein. An hydrophobic cleft, formed by residues located in the second half of the protein could be a potential site for the binding of lipids. PMID- 8001560 TI - Effects of the Tyr64 substitution on the stability of cytochrome c553, a low oxidoreduction-potential cytochrome from Desulfovibrio vulgaris Hildenborough. AB - Cytochrome c553 from sulfate-reducing bacteria is a low-oxidoreduction-potential cytochrome. The primary and tertiary structures show notable differences when compared to mitochondrial cytochromes. Tyr64 replacement in cytochrome c553 provides evidence that this residue is not directly involved in the potential modulation but is mostly implicated in the hydrogen-bond network around the heme. While the different variants obtained did not induce drastic structural modifications, they did affect the stability of the protein. This decrease of stability in acidic and alkaline environments was observed by variations in the optical spectra and by mass spectrometry. In addition, the mobility of aromatic side-chain was found to be increased in the mutant proteins as monitored by two dimensional NMR spectroscopy. PMID- 8001561 TI - Biochemical characterization of human PC-1, an enzyme possessing alkaline phosphodiesterase I and nucleotide pyrophosphatase activities. AB - PC-1 is an ecto-enzyme possessing alkaline phosphodiesterase I and nucleotide pyrophosphatase activities. In this paper, we demonstrate the expression, biochemical characterization and biosynthesis of human PC-1. Previously, there has been uncertainty concerning which of two methionine residues is the initiator. It is now shown that expression of PC-1 is much greater if the first methionine residue is present, and that the sequence between the two methionine residues is translated in both human and mouse, in both transfected cells and cells naturally expressing PC-1. The first methionine residue is therefore the initiator. Human PC-1 is capable of autophosphorylation, and conditions are described in which PC-1 is the only labelled phosphoprotein on the plasma membranes of intact cells, allowing the demonstration that the mature membrane form of human PC-1 is approximately 10 kDa larger than that of the mouse form. Pulse-chase biosynthetic studies and treatment with two different endoglycosidases show that most of this difference is due to N-linked oligosaccharides. The polypeptide backbone of human PC-1 is 20 amino acids longer than that of the mouse PC-1, with most of the difference in polypeptide chain length being in the cytoplasmic domain. The revised cytoplasmic domain of human PC-1 has 76 amino acids, while the mouse cytoplasmic domain has 58 amino acids. Optimal alignment of mouse and human cytoplasmic domains reveals areas of sequence conservation in which the third bases vary. It is suggested that these regions of conservation may point to functionally important sequences in the cytoplasmic domain. PMID- 8001562 TI - Reactions of prostaglandin H synthase with monosubstituted hydrazines and diazenes. Formation of iron(II)-diazene and iron(III)-sigma-alkyl or iron(III) sigma-aryl complexes. AB - The reaction of p-chlorophenylhydrazine with prostaglandin H synthase (PGHS) Fe(III) under aerobic conditions leads to a partial destruction of the heme and to a new complex absorbing at 436 nm. This complex is also obtained by reaction of p-chlorophenyldiazene (pClPhN = NH) with PGHS Fe(III) under anaerobic conditions and by oxidation of the PGHS Fe(II)(pClPhN = NH) diazene complex by Fe(CN)6K3. The similarity between those reactions and those of arylhydrazines and aryldiazenes with other hemoproteins such as cytochrome P450 and hemoglobin and myoglobin, as well as the similarities between the spectroscopic and chemical properties of this complex and those of the sigma-aryl complexes of other hemoproteins such as hemoglobin and myoglobin, strongly suggested a PGHS Fe(III) pClPh structure for this complex. It was completely established after the extraction of its heme, by butan-2-one at 0 degree C under neutral or acidic conditions, which led to the sigma-aryl PGHS-Fe(III)-pClPh complex and to N phenylprotoporphyrin IX, respectively. A mechanism is proposed for the formation of the PGHS Fe(III) pClPh complex; it includes the reduction of PGHS Fe(III) into PGHS Fe(II) with formation of the diazene pClPhN = NH. This diazene can bind to PGHS Fe(II) or be oxidized with formation of pClPh free radicals. These radicals can react with PGHS Fe(II) to form the PGHS Fe(III)-pClPh complex or with the protein, or may initiate free radical oxidations which could lead to destruction of the heme or of the protein. Other alkylhydrazines or arylhydrazines also react with PGHS Fe(III) under aerobic conditions with the formation of PGHS Fe(III)-R or aryl (Ar) complexes and heme destruction. Alkylhydrazines such as methylhydrazine, which lead to very reactive alkyl radicals, lead to very low amounts of PGHS Fe(III)-R complex and high amounts of heme destruction, whereas arylhydrazines bearing electron-withdrawing substituents such as 3,4 dichlorophenylhydrazine, which lead to stabilized aryl radicals, lead to a high amounts of PGHS Fe(III)-Ar complex and low amounts of heme destruction.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8001563 TI - The NADPH: sulfite reductase of Escherichia coli is a paraquat reductase. AB - The NADPH:sulfite reductase of Escherichia coli is a soluble enzyme that has a subunit structure alpha 8 beta 4, where the alpha subunit is a flavoprotein and the beta subunit is a metalloprotein. Overexpression of the holoenzyme in E. coli has greatly simplified the purification of this enzyme. Under aerobic conditions, recombinant sulfite reductase catalyzes the reduction of 1,1'-dimethyl-4,4' bipyridinium dichloride (paraquat) by NADPH, with Km values for paraquat and NADPH of approximately 70 microM and 80 microM, respectively. Since pure flavoprotein alpha subunit, encoded by the cysJ gene, has similar catalytic activities, it is suggested that paraquat receives electrons directly from the alpha subunit. A mutant strain lacking an active cysJ gene is resistant to paraquat. The NADPH:ferredoxin reductase of E. coli is also a paraquat reductase but with much higher Km values for paraquat and lower enzyme activities. These results suggest that the sulfite reductase is a major paraquat reductase in E. coli and is responsible for the toxic activation of the drug. PMID- 8001564 TI - N5-methyltetrahydromethanopterin:coenzyme M methyltransferase from Methanobacterium thermoautotrophicum. Catalytic mechanism and sodium ion dependence. AB - N5-Methyltetrahydromethanopterin:coenzyme M methyltransferase from methanogenic Archaea is a membrane associated, corrinoid-containing enzyme complex which uses a methyl-transfer reaction to drive an energy-conserving sodium ion pump. The purified methyltransferase from Methanobacterium thermoautotrophicum (strain Marburg) exhibited a rhombic EPR signal indicative of a base-on cob(II)amide. In this form, the enzyme was almost completely inactive. Upon addition of Ti(III)citrate, which is a one-electron reductant known to reduce corrinoids to the cob(I)amide form, the EPR signal was completely quenched. In the reduced form, the enzyme was active. When the purified complex was incubated in the presence of both Ti(III) and N5-methyltetrahydromethanopterin (CH3-H4MPT), enzyme bound Co-methyl-5'-hydroxybenzimidazolyl cob(III)amide was formed. Upon incubation of the methylated enzyme with either tetrahydromethanopterin or coenzyme M, the enzyme was demethylated with the concomitant formation of CH3 H4MPT and methylcoenzyme M, respectively. Enzyme demethylation, in contrast to enzyme methylation, was not dependent on the presence of Ti(III). Methyl transfer from the methylated enzyme to coenzyme M was essentially irreversible. These results are interpreted to that the purified enzyme complex is active only when the enzyme-bound corrinoid is in the reduced cob(I)amide form, and that methyl transfer from CH3-H4MPT to coenzyme M proceeds via nucleophilic attack of the cobalt(I) on the N5-methyl substituent of CH3-H4MPT, forming an enzyme-bound CH3 corrinoid as intermediate. Methyl-coenzyme M formation from CH3-H4MPT and coenzyme M, as catalyzed by the purified methyltransferase, was stimulated by sodium ions, half-maximal activity being obtained at approximately 50 microM Na+. We therefore infer that the methyltransferase, as isolated, is capable of vectorial sodium ion translocation. PMID- 8001565 TI - Evidence from in vivo manipulations of lipid composition in mutants that the delta 3-trans-hexadecenoic acid-containing phosphatidylglycerol is involved in the biogenesis of the light-harvesting chlorophyll a/b-protein complex of Chlamydomonas reinhardtii. AB - The phosphatidylglycerol containing the unusual delta 3-trans hexadecenoic fatty acid is specifically found in photosynthetic membranes of eukaryotic organisms. Its involvement in the biogenesis and the structure of the light-harvesting chlorophyll a/b-protein complex has been evidenced by in vivo targeting this lipid to photosynthetic membranes of Chlamydomonas reinhardtii mutants lacking this lipid. In the mf1 and mf2 mutants, this deficiency results in (a) the absence of the oligomeric light-harvesting complex of photosystem 2; (b) an extensive destacking of thylakoid membranes; (c) a very low 77-K fluorescence emission in the photosystem-2 region. We show in this paper that these deficiencies result from modifications in the pigment and polypeptide compositions of the photosystem-2 light-harvesting complex; it contains less chlorophyll b and some of its constitutive polypeptides are absent or reduced in amount, while immunologically related polypeptides of lower molecular mass accumulate. The direct involvement of the lack of trans-C16: 1 phosphatidylglycerol in these deficiencies is evidenced by the partial restoration of normal characteristics of the light-harvesting complex (pigment and polypeptide composition, oligomerization) after liposome-mediated, in vivo incorporation of this lipid into the photosynthetic membranes of the mf2 mutant. Trans-C16:1-phosphatidylglycerol, therefore, is involved in the biogenesis of the photosystem-2 light-harvesting chlorophyll a/b-protein complex through a mechanism that may prevent degradation processes. Its contribution to the structural conformation of neosynthesized monomers and to their organization into stable oligomeric form is discussed. PMID- 8001566 TI - Peripheral nerve sphingomyelin and cerebroside are both formed via two metabolically and kinetically distinct pathways in vivo. AB - We have studied the labeling kinetics of peripheral nerve sphingolipids in vivo. The kinetic analysis of the labeling profiles observed for the various sphingolipids demonstrated that 90% of cerebrosides, but only 30% of sphingomyelin, were synthesized via a de novo synthesized ceramide intermediate following the injection of 1-4 pmol [3H]palmitate into mouse sciatic nerves. The remaining sphingolipid labeling (30% of the total) was due to direct acylation events, using free fatty acids originating from a pool different from those implicated in the de novo ceramide pathway. Direct acylation events ceased within 1 h following substrate administration, while labeling via the ceramide pathway continued through 5 h. The results provide the first in vivo demonstration that the formation of cerebrosides and sphingomyelin in peripheral nerves in situ can be simultaneously assured via two metabolically and kinetically distinct pathways that employ different fatty acid pools. PMID- 8001567 TI - Interdomain loops and conformational changes of glutamate synthase as detected by limited proteolysis. AB - Azospirillum brasilense glutamate synthase, a complex iron-sulfur flavoprotein, was subjected to limited proteolysis using trypsin and chymotrypsin, in the absence or presence of its substrates or their analogs. Time-dependent degradation of glutamate synthase alpha and beta subunits, to yield several fragments of different stability, was observed, the alpha subunit being more sensitive than the beta to proteolytic attack. The main sites of proteolytic cleavage were determined by densitometric analysis of the electrophoretic patterns obtained under denaturing conditions and by N-terminal sequencing of the major proteolytic products. These analyses showed that most of the peptide bonds sensitive to the proteases are clustered in two regions of the alpha subunit, outside the proposed substrate and cofactor binding regions of glutamate synthase [Pelanda, R., Vanoni, M. A., Perego, M., Piubelli, L., Galizzi, A., Curti, B. & Zanetti, G. (1993) J. Biol. Chem. 268, 3099-3106]. Therefore, these protease sensitive sites can be identified as flexible loops, exposed to solvent, connecting adjacent domains of the protein. The presence of the enzyme substrates or their analogs caused significant changes in the proteolytic patterns. NADP+ protected the C-terminal region of glutamate synthase beta subunit from tryptic cleavage, supporting the proposal that it contains the pyridine-nucleotide binding site. Furthermore, NADP+, and to a lesser extent the glutamine analog L methionine sulfone, which binds presumably to the N-terminal region of the alpha subunit, altered the sensitivity to proteolysis of the sites of the alpha subunit proposed to be part of links between domains of glutamate synthase. These results show that long-range conformational changes of glutamate synthase occur on binding of its substrates. The study of several NADPH-dependent diaphorase activities of glutamate synthase was also undertaken in order to test if proteolytic fragments of the enzyme retained their ability to transfer electrons from NADPH to synthetic electron acceptors. Although proteolysis yielded partial loss of all enzyme NADPH-dependent reactions, the kinetic analysis showed that the rates of reduction of iodonitrotetrazolium, ferricyanide and dichlorophenolindophenol were at least twofold faster than the rate of the physiological glutamate synthase reaction. These results indicate that enzyme reduction and intramolecular electron transfer are not rate limiting during catalysis of the physiological glutamate synthase reaction. PMID- 8001568 TI - Description of the kinetic mechanism and the enantioselectivity of quinohaemoprotein ethanol dehydrogenase from Comamonas testosteroni in the oxidation of alcohols and aldehydes. AB - Initial rate studies were performed on the oxidation of (racemic) alcohols as well as aldehydes by quinohaemoprotein ethanol dehydrogenase, type 1, from Comamonas testosteroni with potassium ferricyanide as electron acceptor. The data could be fitted with an equation derived for a mechanism (hexa-uni ping-pong) in which alcohols are oxidized to the corresponding carboxylic acids and the intermediate aldehyde becomes released from the enzyme. However, for some substrates it was necessary to assume that they exert uncompetitive inhibition. The same model was used to fit the data of conversion processes. Reversible inactivation of the enzyme takes place during the conversion, the extent being inversely proportional to the concentration of ferricyanide present at the start. From the values of the kinetic parameters obtained for (R)- and (S)-solketal [2,2 dimethyl-4-(hydroxymethyl)-1,3-dioxolane] and their corresponding aldehydes, it appeared that the second step in (S)-solketal conversion is much faster than the first one and that opposite enantiomeric preferences exist for the alcohol and the aldehyde substrates. Since the initial rate measurements as well as the progress curve analysis gave similar kinetic parameter values and product analysis revealed intermediates in the amounts predicted, it is concluded that the kinetic and enantioselective behaviour of the enzyme is adequately described by the model presented here. Finally, the results indicate that both kinetic approaches should be used in conversions with consecutive reactions since they provide complementary information. PMID- 8001569 TI - A unified pathway for the degradation of ornithine decarboxylase in reticulocyte lysate requires interaction with the polyamine-induced protein, ornithine decarboxylase antizyme. AB - Recent studies have provided convincing evidence to add to a number of earlier observations suggesting that the rapid intracellular degradation of mammalian ornithine decarboxylase (ODC) is further accelerated by the action of ornithine decarboxylase antizyme (ODC-Az), a polyamine-induced protein. However, the mechanism whereby ODC-Az exerts its effect in this proteolytic process is mostly unknown. Here, by using reticulocyte-lysate-based synthesis and degradation systems, we demonstrate that interaction of ODC-Az with ODC results in two related outcomes: (a) ODC is inactivated as a result of its monomerization, and (b) ODC degradation is dramatically accelerated. While ODC inactivation requires the integrity of the ODC-Az binding site of ODC and the ODC binding site of ODC Az, acceleration in ODC degradation also requires the previously characterized carboxyl-terminal destabilizing segment of ODC and a specific segment of ODC-Az that may be functionally distinct from that required for ODC binding. Interestingly, an active ODC variant with a mutant ODC-Az binding site is stable under basal degradation conditions. This, together with the ability of anti-(ODC Az) antibody to specifically inhibit the basal degradation of ODC in the lysate, suggests that ODC-Az is an essential general mediator of ODC degradation. Based on these observations, we propose a model for the degradation of ODC which always require interaction with antizyme. PMID- 8001571 TI - Phosphorylation of inositol 1,4,5-trisphosphate analogues by 3-kinase and dephosphorylation of inositol 1,3,4,5-tetrakisphosphate analogues by 5 phosphatase. AB - A series of 32P-labeled D-myo-inositol 1,3,4,5-tetrakisphosphate [Ins(1,3,4,5)P4] analogues was enzymically prepared from the corresponding D-myo-inositol 1,4,5 trisphosphate [Ins(1,4,5)P3] analogues using recombinant rat brain Ins(1,4,5)P3 3 kinase and [gamma-32P]ATP. Ins(1,4,5)P3 analogues with bulky groups at the 2-OH position, substitutions of phosphates by thiophosphates and D-6-deoxy-myo Ins(1,4,5)P3 were tested. Using [3H]Ins(1,4,5)P3 and ATP gamma S, a [3H]Ins(1,3,4,5)P4 analogue with a thiophosphate at the D-3 position was prepared. The D-4 and/or D-5 phosphate group seemed to be important for 3-kinase activity, while the OH group at position 6 was not crucial. The addition of bulky groups at the 2-OH position did not prevent phosphorylation. The labeled Ins(1,3,4,5)P4 analogues were purified and their degradation by type-I Ins(1,4,5)P3/Ins(1,3,4,5)P4 5-phosphatase was compared with the degradation of Ins(1,3,4,5)P4. Substitution of the phosphate group at positions 1 or 3 by a thiophosphate, or the addition of bulky groups at the 2-OH position did not prevent degradation. D-6-Deoxy-myo-inositol 1,3,4,5-tetrakisphosphate could not be degraded by the 5-phosphatase, indicating the importance of the 6-OH group for 5-phosphatase action. D-6-Deoxy-myo-inositol 1,3,4,5-tetrakisphosphate could be an important tool in elucidating the cellular functions of Ins(1,3,4,5)P4. PMID- 8001570 TI - Further evidence for multiple pathways in soluble methane-monooxygenase-catalysed oxidations from the measurement of deuterium kinetic isotope effects. AB - The data from the deuterium isotope experiments in this study show that the primary kinetic isotope effect for methane oxidation catalysed by soluble methane monooxygenase from Methylococcus capsulatus (Bath) is very small, < 2. In contrast, the primary kinetic isotope effect for -CH3 group oxidation in toluene is large, > 7. A mechanistic pathway in which a substrate radical is formed from hydrogen atom abstraction by a ferryl species is believed to operate for CH4, the toluene -CH3 group and similar alkanes. Direct oxygen atom addition, rather than H atom abstraction, is indicated for aromatic ring oxidations in benzene and toluene and for styrene oxide formation from styrene. Thus, more than one mechanistic pathway appears to operate in soluble methane-monooxygenase-catalysed reactions and, in some cases, the pathway chosen may be dictated by the substrate. In the soluble methane-monooxygenase-catalysed oxidation of toluene the rates of: (a) substrate dissociation from the enzyme-substrate complex, (b) product formation and (c) product release (benzyl alcohol and p-cresol) from the enzyme-product complex are comparable in magnitude. Therefore all three of these steps are partially rate-determining in the soluble methane monooxygenase catalytic cycle for toluene oxidation. PMID- 8001572 TI - Sequence-specific recognition of a repetitive DNA element by a C2H2 zinc-finger protein in Xenopus. AB - XFG 20-1 is one of several hundred C2H2-type zinc finger proteins of unknown biological function in Xenopus. Affinity selection of genomic DNA fragments identifies a 54-bp consensus sequence with high affinity for the XFG 20-1 protein. This sequence is part of a conserved inverted repeat in REM-1, a 0.5-kb repetitive, dispersed genomic DNA element. This finding indicates a possible link between the non-conserved nature of a large subgroup of DNA-binding C2H2 zinc finger proteins and the non-conserved nature of putative genomic target sequences. The 19 zinc finger modules of XFG 20-1 are organized in three structurally distinct groups. Of these, only the first and third ones are required and are sufficient for high-affinity DNA binding. The finding that removal of five internal zinc finger units does not alter the DNase I protection pattern of the complex formed is indicative of a high degree of structural flexibility for linear arrays of zinc fingers, which we imagine to adopt a more rigid structure only upon interaction with their nucleic acid partner molecules. PMID- 8001573 TI - Activation of the O2(-)-generating NADPH oxidase in a semi-recombinant cell-free system. Assessment of the function of Rac in the activation process. AB - The neutrophil NADPH oxidase activation factors, p47, p67 and the small guanosine nucleotide-binding regulatory (G) protein Rac1, were expressed in a baculovirus/insect cell system and purified. In coinfection experiments in which Sf9 cells overexpressed concomitantly p47, p67 and Rac1, the latter was not detected in the p47-p67 complex. The propensity of p47 and p67 to associate together was used to purify recombinant p67 from baculovirus-infected Sf9 cells. 20% of the overexpressed Rac1 in infected Sf9 cells was prenylated and was extracted with low doses of detergent from membranes. Elicitation of full oxidase activity on crude neutrophil membranes using a cell-free system required addition of recombinant p47 and p67, but not that of Rac. In contrast, in the case of KCl washed membranes, addition of Rac, prenylated or unprocessed, together with p47 and p67 was found to enhance oxidase activation up to fivefold. In all experiments, the amount of added arachidonic acid was optimized. In contrast to prenylated Rac, non-prenylated Rac had to be loaded with guanosine 5'-(3 thiotriphosphate) (GTP[S]) to exhibit full activation efficiency. In the cell free system used, Rac was shown to be the mediator of the GTP[S] effect. The results suggest that the plasma membrane of resting neutrophils contains a sufficient amount of prenylated Rac for efficient oxidase activation. We therefore propose that Rac has a membrane-associated role and helps to dock and position p47 and p67 on the flavocytochrome b component of the oxidase complex. PMID- 8001574 TI - Ca2+ binding to cardiac troponin C in the myofilament lattice and its relation to the myofibrillar ATPase activity. AB - The Ca(2+)-binding properties of troponin C in the intact myofilament lattice and their relation to the activation of ATPase were investigated with isolated porcine cardiac myofibrils. Ca2+ binding, which is composed of two classes of binding sites with different affinities (classes 1 and 2), was clearly detected by a novel method for subtracting the large background activity of myofibrillar Ca2+ binding. The classes 1 and 2 were equivalent stoichiometrically to the two high-affinity sites (sites III and IV) and a single low-affinity site (site II) of troponin C. In the presence of ATP, positive cooperativity was observed in the Ca2+ binding of class-2 sites and the Hill equation parameters were in excellent agreement with those for the Ca(2+)-activated myofibrillar ATPase activity, which indicated that the activation of ATPase is a linear function of the Ca2+ occupancy of site II. In the absence of ATP, a marked increase in the affinity of only class-2 sites was observed while the cooperativity was lost. These results provide direct evidence that some feedback mechanism exists between myosin crossbridge attachment and the Ca2+ binding to site II of troponin C, which may thus confer positive cooperativity on the Ca2+ activation of myofibrillar ATPase activity. PMID- 8001575 TI - Pancreatic carboxylester lipase from Atlantic salmon (Salmo salar). cDNA sequence and computer-assisted modelling of tertiary structure. AB - We report the isolation and characterization of a 1795-bp cDNA fragment encoding Atlantic salmon pancreatic carboxylester lipase from salmon pancreas mRNA. The nearly full-length cDNA contained a 540-amino-acid open-reading frame, encompassing the mature protein (by similarity to mammalian carboxylester lipase enzymes). The salmon carboxylester lipase primary structure shared 58% identity with mammalian carboxylester lipases, lacking the proline-rich C-terminal repeats found in human and rat carboxylester lipases. Congruent with other esterase B type enzymes, the salmon carboxylester lipase contained a canonical serine esterase catalytic triad motif consisting of serine, histidine and aspartic acid. Computer-assisted modelling of the tertiary structure for salmon carboxylester lipase was conducted using acetylcholine esterase (Torpedo californica) as a template structure. The model, in conjunction with sequence comparisons and available enzymological data, has been used to locate putative bile-salt-binding and lipid-binding sites. The carboxylester lipase enzymes contain a unique, highly conserved insert region that may be associated with bile-salt binding. In the model structure, this region is located close to the active site, and contains a tyrosine residue with an adjacent carboxylester-lipase-conserved arginine. These traits have previously been predicted for the non-specific (regarding bile-salt hydroxylation) bile-salt-binding site in carboxylester lipase enzymes. At this site, a dihydroxy or trihydroxy bile-salt molecule may bind the tyrosine via hydrophobic interactions, the anionic bile-salt head group may bind the arginine, while hydrogen bonding between the bile-salt 12 alpha hydroxy group and an adjacent aspargine residue is possible. The model does not contain an active site 'lid' structure as found in other lipases. The carboxylester lipase structural homolog to the 'flap' of the lipases from Geotrichum candidum and Candida rugosa contains a carboxylester-lipase-conserved deletion that renders this region unable to cover the active site. Instead, the shortening of this loop leads to solvent exposure of the carboxylester lipase insert region, an additional indication of the functional importance of this region. PMID- 8001576 TI - A blue non-heme iron protein from Desulfovibrio gigas. AB - A novel iron-containing blue protein, named neelaredoxin, was isolated from the sulfate-reducing bacterium Desulfovibrio gigas. It is a monomeric protein with a molecular mass of 15 kDa containing two iron atoms/molecule. The N-terminal sequence of neelaredoxin has similarity to the second domain of desulfoferrodoxin, a protein purified from Desulfovibrio vulgaris Hildenborough. This finding supports the hypothesis that the gene coding for desulfoferrodoxin (rbo) might have arisen from a gene fusion [Brumlik, M. J., Leroy, G., Bruschi, M. & Voordouw, G. (1990) J. Bacteriol. 172, 7289-7292]. The visible spectrum exhibits a single band at 666 nm, responsible for the blue color of the protein, which is completely bleached upon reduction with sodium ascorbate. In the oxidized state the EPR spectrum is complex, exhibiting well-resolved features at g = 7.6, 7.0, 5.9, and 5.8 which are assigned to two high-spin (S = 5/2) mononuclear-iron (III) centers with different rhombic distortions (E/D approximately 0.05 and approximately 0.08). The two iron atoms contribute identically to the visible spectrum as judged from visible redox titrations, from which a reduction potential of +190 mV was determined for both iron sites at pH 7.5. At high pH the visible and the EPR spectra become pH-dependent with a pKa above 9: the 666-nm band shifts to 590 nm and the EPR signals are converted into a signal with gmax approximately 4.7. Neelaredoxin is readily reduced both by H2/hydrogenase/cytochrome c3 and by NADH/NADH-rubredoxin oxidoreductase. PMID- 8001578 TI - Primary structure and inhibitory properties of a subtilisin-chymotrypsin inhibitor from Streptomyces virginiae. AB - A novel serine protease inhibitor SIL8, which was isolated from the culture medium of Streptomyces virginiae and shown to be a member of the Streptomyces subtilisin-inhibitor-like (SIL) inhibitor family by sequence analysis of its amino-terminal region [Taguchi, S., Kikuchi, H., Kojima, S., Kumagai, I., Nakase, T., Miura, K. & Momose, H. (1993) Biosci. Biotech. Biochem. 57, 522-524], is the first SIL inhibitor demonstrated to show marked inhibitory activity toward alpha chymotrypsin, in addition to strong inhibitory activity toward subtilisin BPN', a common property of inhibitors of the Streptomyces subtilisin inhibitor (SSI) family. In this study, the complete amino acid sequence of SIL8 was determined from the sequence analysis of peptides obtained by specific cleavage at the reactive site and by enzymic digestion. SIL8 was shown to exist as a dimer protein, each subunit of which was composed of 111 amino acids, and to have less than 50% similarity with other SSI-family inhibitors, indicating its most distant relationship to other members of this family. Insertion of two residues was observed in the flexible loop region of SIL8, and amino acid replacements were found not only on the molecular surface but also in the beta-sheet and hydrophobic core, suggesting that packing rearrangements of the side chains may occur in these regions to maintain the tertiary and quaternary structures. The inhibitor constants Ki obtained using synthetic substrates are 92 pM for subtilisin BPN' and 11 nM for alpha-chymotrypsin. The P1 site was was identified as methionine, which was in good agreement with the substrate specificity of alpha-chymotrypsin. SSI, which also possesses a methionine residue at the P1 site, inhibits alpha-chymotrypsin poorly (inhibitor constant, 4.0 microM). Such a difference in the inhibitory properties of SIL8 and SSI toward alpha-chymotrypsin is discussed on the basis of the structures of the inhibitors. PMID- 8001577 TI - Pathogen-defence gene prp1-1 from potato encodes an auxin-responsive glutathione S-transferase. AB - Genetic studies have previously implicated the prp1 gene family in the defence of potato against infection with the late blight fungus Phytophthora infestans. Here, we show that the concentrations of PRP1 mRNA as well as protein rapidly increase in potato leaves after fungal infection and stay at high levels during an extended period of the infection cycle. After separation of subcellular components by differential centrifugation, PRP1 protein was identified in the cytosolic fraction. Expression studies with chimeric promoter/beta-glucuronidase gene constructs in transgenic potato plants provided evidence that transcription of the prp1-1 gene, representing one member of the prp1 gene family, is at least partly responsible for the accumulation of PRP1 mRNA and protein upon fungal infection. After expression of the prp1-1-coding sequence in Escherichia coli, the corresponding 26-kDa protein exhibited glutathione S-transferase activity with Km values of 9.8 mM and 0.11 mM for the artificial standard substrate 1 chloro-2,4-dinitrobenzene and glutathione, respectively. Photoaffinity labeling of the protein with tritiated 5-azido-indole-3-acetic acid suggested that the phytohormone indole-3-acetic acid or a structurally related compound serve as a regulator or substrate of the prp1-1 encoded glutathione S-transferase. This assumption was further supported by the inhibitory effect of the phytohormone on the enzyme activity in vitro. The implications of these findings for a potential involvement of indole-3-acetic acid in the control of defence reactions are discussed. PMID- 8001579 TI - Purification and properties of alternanase, a novel endo-alpha-1,3-alpha-1,6-D glucanase. AB - A newly isolated soil bacterium strain NRRL B-21195, tentatively identified as a Bacillus species, was found to be a constitutive producer of a novel type of glycanase that hydrolyses in an endo-fashion the polysaccharide alternan, an alpha-1,3-alpha-1,6-D-glucan, referred to in the literature as B-1355 dextran (fraction S), synthesized from sucrose by alternansucrase of Leuconostoc mesenteroides. The glycanase, named alternanase, has been purified to homogeneity from a cell-free culture fluid of the bacillus grown in a liquid medium containing D-glucose, and has been characterized. The enzyme has a molecular mass of 110000 Da (SDS/PAGE) and an isoelectric point of approximately 4.0. Optimum activity occurs at pH 7 and at a temperature of 40 degrees C. The enzyme is stable up to 50 degrees C but loses activity rapidly at 60 degrees C. Its action is inhibited by EDTA and stimulated by Ca2+. The enzyme requires, for its action, D-glucan chains in which alpha-1,3-linkages alternate with alpha-1,6-linkages; i.e., it is specific for alternan. Monitoring of alternan hydrolysis by determination of liberated reducing sugars pointed to an unusually low extent of hydrolysis and a low specific activity of the enzyme. As shown in the accompanying paper [Cote, G. L. & Biely, P. (1994) Eur. J. Biochem. 226, 641-648] the reason for this finding is that the main hydrolytic products are non reducing, novel types of cyclic oligosaccharides. PMID- 8001580 TI - Enzymically produced cyclic alpha-1,3-linked and alpha-1,6-linked oligosaccharides of D-glucose. AB - A new type of bacterial enzyme hydrolyzed alternan (Leuconostoc mesenteroides NRRL B-1355 fraction S dextran, an alternating alpha-1,3-alpha-1,6-D-glucan) to give rise to a series of oligosaccharides. The oligosaccharide formed in the greatest proportion was a cyclic tetrasaccharide of D-glucosyl residues linked in an alternating alpha-1,3-alpha-1,6 fashion. Other saccharide products included isomaltose and alpha-D-glucopyranosyl-1,3-alpha-D-glucopyranosyl-1,6-D-glucose. Oligosaccharides of higher degrees of polymerization were also formed, and included alpha-D-glucosylated derivatives of the cyclic tetrasaccharide. This is the first report of a naturally produced cyclic tetrasaccharide. PMID- 8001581 TI - A method for increasing the concentration of a specific internal metabolite in steady-state systems. AB - An approach is described by which it is possible to increase the concentration of any internal metabolite without affecting the concentrations of other metabolites and fluxes in the organism. This approach requires the manipulation of only a limited number of enzyme activities. The method shows which enzymes to manipulate and the extent of the manipulation required to achieve a given increase in a chosen metabolite. A case study involving tryptophan overproduction in Saccharomyces cerevisae is given as a practical example of how this method could be used. PMID- 8001583 TI - Effects of glucose on the activation and translocation of glycogen synthase in diabetic rat hepatocytes. AB - Incubation of hepatocytes from diabetic rats with glucose results in the translocation of glycogen synthase from soluble fractions to fractions which sediment at 9200 g. The extent of the translocation correlates positively with the intracellular concentration of glucose 6-phosphate. No difference was found between healthy and diabetic rats in the capacity of glycogen synthase to translocate to pellets in response to an increase in glucose 6-phosphate. In diabetic hepatocytes, glycogen synthase in the supernatant fractions was not activated upon incubation of the cells with glucose, whereas this sugar was able to activate the enzyme found in the fractions that could be pelleted. In the 9200 g pellets, the glycogen synthase activity ratio (-glucose 6-phosphate/+glucose 6 phosphate) from both healthy and diabetic animals correlated with the intracellular glucose 6-phosphate levels. In the supernatants, the glycogen synthase activity ratio from healthy cells also correlated with glucose 6 phosphate levels. In contrast, in diabetic cells the activation state of the soluble enzyme remained essentially unchanged despite the accumulation of glucose 6-phosphate. PMID- 8001584 TI - Isolation of a novel Plasmodium falciparum gene encoding a protein homologous to the Tat-binding protein family. AB - We have cloned a Plasmodium falciparum gene that belongs to the nuclear Tat binding protein (TBP) gene family. This gene, PfTBP, is (A + T)-rich and encodes a 49.5-kDa protein. The predicted protein encoded by this gene has highest similarity to the slime mold protein DdTBP10 (86%) and to the yeast protein SUG1 (81.8%), both of which belong to the Tat-binding protein family. In agreement with the characteristics of this family, PfTBP contains a highly conserved domain of approximately 200 amino acids, in which are found the motifs A and B of ATPases, and amino acid sequences characteristic of a large family of RNA or DNA helicases, suggesting a role in RNA or DNA unwinding. Like DdTBP10, the PfTBP protein has a heptad repeat of four leucine residues, reminiscent of a leucine zipper motif known to mediate dimerization. We have further characterized PfTBP gene expression by Northern-blot analysis. This gene is expressed in a stage specific manner, with higher expression in the late trophozoite stage. The recombinant PfTBP gene has been expressed in Escherichia coli and a polyclonal antiserum has been raised in rabbits against the recombinant protein. This antibody has been used to study the protein in the parasite. The gene product is expressed in a stage-specific manner with higher expression in the late trophozoite and schizont stages, and is localized in the nucleus of the erythrocytic stage parasite. Thus the protein might have a function in DNA synthesis and/or in transcription, as is the case for other Tat-binding proteins. PMID- 8001582 TI - The folding of the bifunctional TRP3 protein in yeast is influenced by a translational pause which lies in a region of structural divergence with Escherichia coli indoleglycerol-phosphate synthase. AB - The yeast TRP3 gene encodes a bifunctional protein with anthranilate synthase II and indoleglycerol-phosphate synthase activities. Replacing ten consecutive non preferred codons in the indoleglycerol-phosphate synthase region of the TRP3 gene with synonymous preferred codons (to create the TRP3pr gene; translational pause replaced) causes a 1.5-fold reduction in relative indoleglycerol-phosphate synthase activity [Crombie, T., Swaffield, J.C. & Brown, A.J.P. (1992) J. Mol. Biol. 228, 7-12]. Here, we report that both the anthranilate synthase II and indoleglycerol-phosphate synthase domains are affected to similar extents when the translational pause is removed. Also, structural modelling of the yeast indoleglycerol-phosphate synthase domain against the X-ray crystal structure of indoleglycerol-phosphate synthase from Escherichia coli indicates that the translational pause lies in a region of structural divergence between similar structures. To probe the role of cytoplasmic heat-shock protein 70 (Hsp 70) chaperones in Trp3 protein folding, anthranilate synthase and indoleglycerol phosphate synthase activities were measured in ssa and ssb mutants. Neither indoleglycerol-phosphate synthase nor anthranilate synthase were affected significantly in the ssb mutant. However, depletion of Hsp70 proteins encoded by the SSA genes led to decreased anthranilate synthase and indoleglycerol-phosphate synthase activities from the TRP3 gene, suggesting that both domains depend to some extent upon the SSA chaperone family. The data are consistent with roles for both the translational pause and Ssa chaperones in Trp3 protein folding in vivo. PMID- 8001585 TI - Interaction of plant profilin with mammalian actin. AB - The mode of interaction of birch and bovine profilins with actin was compared using a number of techniques. Birch profilin was purified from pollen or as a recombinant protein from Escherichia coli, using poly(L-proline) affinity chromatography and a monoclonal antibody for the identification of the isolated product. On two-dimensional gels, the genuine and recombinant proteins were identical in molecular mass and isoelectric point and revealed that birch profilin, in contrast to the basic profilins found in mammals, is an acidic protein, analogous to maize profilins. Bovine profilin was obtained from calf thymus. In viscometric assays, the birch protein was seen to modulate actin filament formation analogous to animal profilin. Birch profilin increased the critical concentration required for muscle and brain actin polymerization in a concentration-dependent manner, supporting the notion of the formation of a heterologous complex between the plant protein and animal actin. The effect was Mg(2+)-sensitive, as had been described for homologous complexes. The dissociation constants obtained for the plant/vertebrate and the vertebrate/vertebrate system were both in the micromolar range. The affinity of birch profilin for muscle actin was slightly lower than that for nonmuscle (brain) actin. A binary complex of birch profilin and skeletal muscle actin could be isolated by gel chromatography. Cross-linking experiments with actin, birch profilin, the G-actin binding peptide thymosin beta 4 and gelsolin segment 1, the N-terminal fragment of an actin capping protein, showed that profilin competed with thymosin beta 4, but had no effect on segment 1 binding to actin. These data indicate that the actin-binding domains in plant and animal profilins are functionally highly conserved, although the overall sequence similarity is less than 25%. PMID- 8001586 TI - Flies in the group Cyclorrhapha use (3S)-3-hydroxyretinal as a unique visual pigment chromophore. AB - In the class Insecta, retinal and 3-hydroxyretinal are used as chromophores of visual pigments, but the absolute structure of the 3-hydroxyretinal chromophore has yet to be clarified. This study investigates the chirality of 3 hydroxyretinal in the compound eyes of five representative orders of insects. In the orders Odonata, Hemiptera, Neuroptera and Lepidoptera, and suborders Nematocera and Brachycera of the Diptera, only (3R)-3-hydroxyretinal isomers were detected, but dipterans of the suborder Cyclorrhapha (higher flies) had the (3S) 11-cis enantiomer and a mixture of (3R)-all-trans and (3S)-all-trans 3 hydroxyretinal enantiomers; the ratio of the (3R) enantiomer to the sum of both enantiomers of the all-trans isomer was in the range 9-32%. Despite differences in feeding habits, including one species that is a butterfly parasite, all higher flies analysed to date share the same pattern of 3-hydroxyretinal enantiomers, making them a unique group with regard to the nature of the visual pigment chromophore. PMID- 8001587 TI - Heterologous expression of the human D2S dopamine receptor in protease-deficient Saccharomyces cerevisiae strains. AB - The cDNA for the human D2S dopamine receptor has been functionally expressed in the unicellular yeast Saccharomyces cerevisiae. The original D2S gene and an elongated D2S gene with an N-terminal fusion to the first 24 amino acids of the STE2 gene from S. cerevisiae were introduced into the episomal yeast expression vector YEp51 under the control of the GAL10 promoter. Expression studies performed in a wild-type strain and in two protease-deficient strains of S. cerevisiae revealed that the receptor was functionally expressed with respect to its ligand-binding properties. The KD values for the binding of the dopamine antagonist [3H]spiperone were calculated to be 1.6 nM for the D2S receptor alone and 1.9 nM for the STE2-D2S chimaera. Both membrane proteins could be further characterized by ligand-displacement studies using certain dopamine agonists and antagonists. D2S dopamine-receptor-specific polyclonal antibodies were used to monitor the heterologous expression of the receptor. Western-blot analysis of membranes prepared from transformed yeast cells producing either the receptor protein alone or the receptor fusion protein revealed apparent molecular masses of 40 kDa (D2S receptor alone) and 42 kDa (STE2/D2S receptor fusion protein). It could be shown that, in comparison to the expression in a wild-type S. cerevisiae strain, the amount of receptor degradation was drastically reduced in the protease-deficient strains. The localizations of the heterologously produced dopamine receptor and of the chimaera in the recombinant yeast were studied by immunogold electron microscopy and were found to be restricted mainly to the vacuole of the cells. PMID- 8001588 TI - Linoleic acid transport by human placental syncytiotrophoblast membranes. AB - The placenta syncytiotrophoblast is the site of exchange of nutrients, lipids and minerals between the mother and the fetus. In order to characterize the transport of fatty acids by the placenta, we purified bipolar syncytiotrophoblast brush border and basal plasma membranes from human placenta. These purified brush border and basal plasma membranes enriched 3-fold and 22-fold, respectively, in sodium/potassium-ATPase and 27-fold and 6-fold in alkaline phosphatase activity, compared with the placental homogenates. Fatty acid transport was performed at different fatty acid/albumin ratios to evaluate the optimal uptake conditions. The maximal transport efficiency, for linoleic acid bound to albumin by sonication, was obtained with a 6:1 fatty acid/albumin ratio in brush border and basal plasma membranes. The linoleic acid transport observed with brush border membranes followed Michaelis-Menten kinetics, with a Michaelis constant of 7.89 +/- 0.01 microM and a maximal incorporation rate of 30.80 +/- 6.39 pmol.mg-1.min 1. Linoleic acid transport was very low in basal plasma membranes and we obtained a Michaelis constant of 0.95 +/- 0.01 microM and a maximal incorporation rate of 1.62 +/- 5.06 pmol.mg-1.min-1. In order to show that linoleic acid accumulated within brush border and plasma membrane vesicles, and to eliminate the possibility of a non-specific binding of fatty acid to these membranes, we demonstrated by an osmolarity experiment, the decrease of the linoleic acid transport in brush border and basal plasma membranes obtained in the presence of 455 microM essential fatty acid at 23 degrees C for 180 min. The results presented in this study suggest that linoleic acid is transported significantly by syncytiotrophoblast brush border membranes and basal plasma membranes. Thus, it may represent a unidirectional transport from mother to fetus through the brush border membranes facing the mother, followed by transport at a slower rate through basal plasma membranes facing the fetus. PMID- 8001589 TI - Arrangement of mRNA at the decoding site of human ribosomes. 18S rRNA nucleotides and ribosomal proteins cross-linked to oligouridylate derivatives with alkylating groups at either the 3' or the 5' termini. AB - Affinity labeling of human placental 80S ribosomes with mRNA analogs of up to 12 uridyl residues, i.e. alkylating derivatives of oligouridylates bearing either 4 (N-2-chloroethyl-N-methylamino)benzylmethylphosphamide group at the 5'-termini or 2',3'-O-[4-(N-2-chloroethyl-N-methylamino)]benzylidene residue attached to the 3' termini, in the presence of cognate Phe-tRNA(Phe) has been investigated. All the mRNA analogs modified only the 40S subunit. The fraction of 18S rRNA modified by the mRNA analogs with the alkylating group at the 5'-end decreased dramatically with extension of the reagent oligouridylate moiety. Nucleotides of 18S rRNA alkylated with the mRNA analogs were determined using a reverse transcription technique. For the mRNA analogs with the alkylating groups at the 3'-termini, G1702 and G1763/G1764 were identified as the cross-linking sites. The intensities of the bands corresponding to reverse transcriptase stops depended on the length of the reagent oligouridylate moieties. Cross-linking sites of the mRNA analogs with the alkylating group at the 5'-termini on 18S rRNA were A1023, C1026, C1057 and A1058 for the (pU)3 and (pU)4 derivatives and a single nucleotide C1057 for the (pU)6 one. Ribosomal protein S26 was found as the main target of modification with the same derivatives of (pU)6 and (pU)12. PMID- 8001590 TI - The reaction of hydrogen peroxide with pulsed cytochrome bo from Escherichia coli. AB - The reaction of hydrogen peroxide (H2O2) with pulsed cytochrome bo leads to characteristic spectral changes in the enzyme. The difference spectrum shows minima at 401, 494 and 628 nm, and maxima at 420, approximately 468, 526 and 556 nm. delta epsilon 420-epsilon 401 is in the range 73-86 mM-1.cm-1 and delta epsilon 556-epsilon 628 is 7.7-9.6 mM-1.cm-1 (taking delta epsilon 560-epsilon 580 for the reduced minus oxidised spectrum to be 20.5 mM-1.cm-1). The stoichiometry of the reaction, determined by titration of the spectral changes, is 1:1. The second order rate constant for the reaction, which is 1.0-1.5 x 10(3) M-1.s-1 at 20 degrees C, is independent of pH over the range 6.5-8.0. The product of the reaction decays with a first-order rate constant in the range 1-4 x 10(-4) s-1, so the Kd value is apparently in the range 0.05-0.40 microM. The spectral changes observed immediately after quinol-induced turnover, or during steady state turnover induced by hydrazine or by carbon monoxide, are qualitatively the same as those induced by H2O2 though of lower amplitude. H2O2 addition perturbs the hydrazine-induced or CO-induced steady states by increasing the amplitude of the spectral changes, but there is no qualitative change. From this observation, and the 1:1 stoichiometry of the reaction, we conclude that the intermediate induced by H2O2, which we term F., requires donation of only two electrons to the enzyme from an external source. PMID- 8001591 TI - Urinary excretion and metabolism of orally administered mefenorex. AB - Metabolic pathways and the pharmacokinetic profile of mefenorex ((+/-)N-(3 chloropropyl)-1-methyl-2-phenylethylamine), and its main metabolite amphetamine (1-methyl-2-phenylethylamine) have been studied in two healthy volunteers, after a single oral dose of mefenorex (1.2 mg/kg body weight for a male subject and 2.4 mg/kg body weight for a female subject). Urinary concentrations were determined by gas chromatography (GC) and metabolite structure was identified by GC/MS following derivatization of urine extracts. The ratio of this metabolite to unchanged drug in urine samples, collected up to 5 h following administration, was essentially the same after either of the administered doses. The calculated Kel for mefenorex after the higher dose was in the range of 0.191-0.272 h-1, with a biological half life (t1/2) of 3.98-2.55 h, depending on the method of calculation used. The elimination of amphetamine was much slower with a Kel ranging from 0.039-0.073 h-1 and a t1/2 from 9.5-17.8 h. Depending on the dose administered, the rate constant of metabolite formation was 0.129 and 0.685 h-1 for low and high doses, respectively. Urinary excretion of Rondimen amounted to 11.9% within 72 h after administration. Of this amount, 1.5% represented unchanged drug and 10.4% represented metabolites. In addition to amphetamine 3 other metabolites were identified: p-hydroxy mefenorex, p-hydroxy amphetamine and p-hydroxy-m-methoxy mefenorex. PMID- 8001592 TI - Action of methotrexate on cytochrome P-450 monooxygenases in rats. Study performed with [13C]-aminopyrine micro breath test. AB - The aim of this work was to study the action of methotrexate on the cytochrome P 450 hepatic monooxygenases and to follow the evolution of the metabolic processes with time, after oral and intra-peritoneal administration of these drugs to rats. In order to perform this study, we used a new technique the [13C]-aminopyrine breath test (ABT). At the end of the in vivo study, the rats were sacrificed and the cytochrome P-450 concentration as well as microsomal enzymatic activities of aminopyrine N-demethylase, 7-ethoxyresorufin desalkylase, 7-ethoxycoumarin desalkylase, 7-pentoxyresorufin desalkylase were determined. A histological study of the liver was also carried out. Finally, haematological and biochemical parameters were also determined. In this study, 3 series of 6 rats were used: a control group, a group receiving 70 mg/kg of methotrexate by intra-peritoneal route, and a group of rats treated orally with 1 mg/kg of methotrexate every 2 days. For each observation, the variation of the ABT scores and of the cytochrome P-450 amounts as well as the microsomal aminopyrine N-demethylase activity were in good agreement. PMID- 8001593 TI - Metabolite profiles of two [14C]-labelled catechol O-methyltransferase inhibitors, nitecapone and entacapone, in rat and mouse urine and rat bile. AB - The metabolites of two inhibitors of catechol O-methyltransferase, nitecapone [3 (3,4-dihydroxy-5-nitrobenzylidene)2,4-pentanedione] and entacapone [(E)-2-cyano N,N-diethyl-3-(3,4-dihydroxy-5-nitrophenyl)propenamide++ +], excreted in urine and bile by rats and in urine by mice, were compared and quantified by using HPLC with radiochemical detection after administration of [14C]-labelled compounds. With the exception of 3-O-methylated nitecapone, no major metabolites were found in rat bile that were not found in rat urine. For both compounds the major biotransformations were the same in the mouse and the rat. However, a bisulfite adduct of nitecapone was found in rat urine only, and reduction of the C = C and C = O groups of the nitecapone side chain was more extensive in the mouse. After entacapone administration, the products of amide N-dealkylation were more abundant in rat urine than in mouse urine. Most of the dose was excreted in urine and bile as O-conjugates. Most abundant were the O-glucuronides, while smaller amounts of O-sulfates and O-methylated metabolites were found in both species. One non-glucuronide glycoside of entacapone was found in urine of both rats and mice. PMID- 8001594 TI - Metabolism of the steroidal aromatase inhibitor atamestane in rats, cynomolgus monkeys and humans. Isolation and identification of the major metabolites. AB - The metabolism of the steroidal aromatase inhibitor atamestane was studied in the rat, the cynomolgus monkey and in the human. Metabolite patterns were recorded in plasma, urine and bile (rat only) before and after enzymatic cleavage of sulfate and glucuronide conjugates. Atamestane was rapidly and extensively metabolized by all three species. Major metabolites which were observed in the human, could be isolated from urine pools of treated monkeys by preparative high performance liquid chromatography and were identified by GC/MS and 1H-NMR analysis. The metabolite patterns observed in the animals and in the human were similar, although some species- and sex-related differences were observed. There seem to be two principal routes by which atamestane is metabolized: one route is characterized by the attack of 17 beta-hydroxysteroid dehydrogenase, the other route includes hydroxylation of the 1-methyl group with subsequent attack by 5 beta-reductase, followed by a hydroxylation at position C-6. Some of the metabolites which were identified still had some pharmacological activity, although less marked than the parent compound. PMID- 8001595 TI - Alpha interferon has no effect on lidocaine metabolism in the rat. AB - Interferons (IFN) inhibit activity of many isoenzymes of the hepatic microsomal cytochrome P-450 system. This inhibition is species specific. Lidocaine is metabolized by cytochrome P-450 III A 4. We investigated in the rat the effect of rat alpha-IFN on lidocaine elimination and on its extraction by the isolated perfused rat liver. To determine elimination, the femoral artery and vein were cannulated. 24 h later, the conscious rat was given lidocaine through the venous catheter and blood was drawn from the arterial catheter for lidocaine determination every 3 min for 20 min. 7 rats were pre-treated with intramuscular rat alpha-IFN 7.5 x 10(5) U, 24 h prior to the experiment and another 4 rats were given saline i.m. The lidocaine elimination rate constant was unchanged, 0.065 min-1 and 0.063 min-1 for the control and IFN groups, respectively. To investigate lidocaine extraction, the isolated perfused rat liver was used. Perfusate samples from the portal and hepatic veins were drawn at 2 min intervals for 20 min, and lidocaine extraction determined. Extraction was determined in two groups of 6 rats each. The first group served as control and these rats were injected with saline only, while in the second group, the rats were pre-treated with rat alpha-IFN 7.5 x 10(5) U. Lidocaine extraction by the isolated perfused rat liver remained unchanged, 97.0 +/- 0.7% and 94.0 +/- 2.4% in the control and IFN treated groups, respectively. It is concluded that the rat alpha-IFN affects neither the elimination nor the extraction of lidocaine. PMID- 8001596 TI - Inter- and intra-subject variability of metoprolol kinetics after intravenous administration. AB - The pharmacokinetics of metoprolol were assessed from the data of 3 experiments in which intravenous deuterated metoprolol was given concomitantly with various oral metoprolol formulations to healthy volunteers. The plasma levels after intravenous administration were well described by a biexponential equation. However, a deviation from a pure biphasic decline was observed over a short period of time, immediately after the rapid elimination phase. The inter- and intra-subject variability of the parameters describing the two-compartment model was large. The intra-subject variability of the terminal half-life and the plasma clearance was lower than their inter-subject variability. The plasma clearance was linearly related to 1/t1/2. Contrarily to the other parameters of the model, t1/2 appeared to be a characteristic of the subject. PMID- 8001597 TI - Aflatoxin induces depletion of activities of phase I biotransformation enzymes in growing rats. AB - Aflatoxins are suspected human carcinogens and are also known to possess diverse toxicological activities. In the present communication an attempt has been made to evaluate the effects of aflatoxin B1 (AFB1) on hepatic microsomal drug metabolizing enzymes in growing rats. The weanling rats were exposed to 60, 300 or 600 micrograms AFB1/kg body weight, per os, on alternate days for 4 weeks, in 0.2 ml corn oil. A significant depression in the activities of aryl hydrocarbon hydroxylase (AHH), aniline hydroxylase (AH) and aminopyrene-N-demethylase (AND) was observed at 300 micrograms and 600 micrograms doses of AFB1. However, no significant change was recorded in glutathione-S-transferase (GST) activity and total sulphydryl (SH) content upon AFB1 exposure in weanling rats. Thus, AFB1 appears to have more pronounced effect on the phase I, rather than phase II, biotransformation enzyme system in weanling rats. The depression of drug metabolizing enzymes together with suppression of immunity by AFB1, as reported earlier by us, may increase the susceptibility of the host to toxic chemicals, drugs and infectious agents, particularly during the post-natal period. PMID- 8001598 TI - Pharmacokinetics of thymoxamine in rabbits after ophthalmic and intravenous administration. AB - The pharmacokinetics of thymoxamine hydrochloride were studied in rabbits by the assessment of its ocular and systemic absorption after instillation of thymoxamine hydrochloride 0.5% eye drops. Plasma levels were compared with those observed after i.v. bolus administration of thymoxamine hydrochloride at 2.5 mg/kg. Deacetylthymoxamine is the main metabolite of thymoxamine, generated by esterase hydrolysis. It was evaluated, as an indication of the parent drug, in aqueous humor and plasma by an HPLC method with fluorescence detection (detection limit = 5 ng/ml). Thymoxamine was found to permeate the cornea and to be hydrolysed very quickly, showing very good absorption with a maximum aqueous humor concentration of deacetylthymoxamine of 2329 ng/ml 15 min after eye drop instillation. The study of the systemic absorption of thymoxamine allowed the exclusion of the possibility of systemic side effects following ocular treatment. In fact, considering the detection limit of the method, the plasma levels of deacetylthymoxamine are certainly more than 100-times lower than those observed with intravenous treatment. PMID- 8001599 TI - Pharmacokinetic analysis of a new acenocoumarol tablet formulation during a bioequivalence study. AB - The pharmacokinetics of a new tablet formulation of acenocoumarol racemate, an oral anticoagulant agent, has been investigated in 8 normal healthy subjects. The drug was given as a single oral dose of 12 mg. 12 blood samples were collected after administration Plasma acenocoumarol concentrations were determined by a sensitive HPLC method. Areas under the plasma level-time curves for each subject were evaluated by means of the trapezoidal rule. The peak plasma concentration of 244.19-644.23 micrograms/l was reached 1-4 h after drug administration. The terminal phase half-life was 6.29-14.22 h and a systemic clearance was 1.86-5.62 l/h. The new table formulation of acenocoumarol seems to be bioequivalent when compared to the one used so far. For the prediction of systemic availability and estimation of the first-pass metabolism, from plasma level data, a hepatic blood flow rate limited model were used. The systemic availability was 94.22-98.01% and the elimination of the drug on its first-pass through the liver was 1.99-5.78%. PMID- 8001600 TI - Contribution of scintigraphy to verify the reliability of different preparation processes for enteric coated capsules. AB - The aim of this work was to use radiopharmaceuticals such as technetium (99mTc) and indium (DTPA-Ca111In) to visualize, with a gamma-camera, the disintegration area and time of 3 types of enteric coated hard gelatin capsules (obtained by 3 different preparation processes) and thus, to verify that they are really resistant in gastric fluids and soluble in intestinal zones. Results are well correlated with those previously obtained in vitro (disintegration, dissolution) and in vivo (profiles of plasmatic concentrations versus time). PMID- 8001602 TI - Epilepsy 1993. State of the art. 6th cooperative meeting on epilepsy and EEG of Austria, Belgium, Luxemburg and Switzerland. June 3-6, 1993, Montreux, Switzerland. Proceedings. PMID- 8001601 TI - Osseous concentrations of gentamicin after implantation of acrylic bone cement in sheep femora. AB - 17 sheep received femoral implantation of 'Cerafix Genta', containing gentamicin 0.6 or 1.2 g per dose either unilaterally (first 3 sheep) or bilaterally (remaining 14 sheep). Highest concentrations in bone were measured after 24 and 48 post-operative hours (respectively 36 and 72 mg/kg for Cerafix 0.6 g and 1.2 g). Gentamicin concentrations in bone marrow and femoral heads were in the same range. Blood and urine concentrations of gentamicin measured in sheep were comparable to those obtained in man. An extrapolation of the gentamicin behaviour from sheep to humans, might be possible: the sheep weight and femoral dimensions were comparable to those of humans and the method of implantation was similar in man and animal. For up to 18 months after operation, gentamicin levels in bone were always higher than critical concentration (4 mg/kg). For the early post operative period, blood and urine levels always remained below gentamicin toxic concentrations. PMID- 8001603 TI - Seizure types and epileptic syndromes in adults. AB - Classifications of epileptic seizures and syndromes have been made in 2,956 patients of the adult seizure unit in Innsbruck, Austria, according to the ILAE proposals. In general, both classification schemes can be used in daily clinical work. Some difficulties arise with the subdivision of absence seizures and the lack of subdivision of myoclonic seizures. With idiopathic epilepsies characterized by generalized tonic-clonic seizures, the strict diagnostic separation according to diurnal occurrence occasionally leads to arbitrary classifications. The subdivison of localization-related epilepsies should rather be based on etiological factors than on the suspected anatomical site of the epileptogenic focus. PMID- 8001604 TI - Electroencephalogram and epilepsy. AB - In spite of its low degree of specificity and its poor sensibility, the electroencephalogram has remained, for half a century, the epileptologist's working tool. In this paper, the places of simple activation procedures are recalled, especially sleep activations. Recent studies have shown that EEG is important in diagnosis assessment and in treatment management. PMID- 8001605 TI - EEG mapping--a new way of monitoring in epilepsy. AB - A method for comparison of EEG mapping findings on the basis of numeric data, i.e. the numeric power values measured at the electrode sites for each frequency band, is described. Examples for the clinical use of comparison studies in epileptic patients are given. The problems regarding methodological issues are discussed. PMID- 8001606 TI - Role of long-term EEG monitoring in diagnosis and treatment of epilepsy. AB - The value of long-term EEG recordings for diagnosis and differential diagnosis of epilepsy is described. It is emphasized that long-term EEF monitoring increases the scope of EEG techniques and improves the diagnostic value of standard EEG recordings providing up to 90% positive diagnostic information. In particular, the value of ambulatory cassette recording is stressed. Allowing quantification of epileptic activity recorded in real-life situation, useful information not available by means of standard EEG recordings can be obtained. Recording and scoring all-night sleep, it enables studying abnormalities of sleep patterns. In addition the value of long-term EEG recordings in therapy and control of epileptic patients is pointed out and discussed. PMID- 8001607 TI - Seizure types and epileptic syndromes. AB - The main epileptic syndromes occurring during brain maturation, i.e. during the neonatal period, infancy, childhood and adolescence, are reviewed. The concept of epileptic syndromes is of pragmatic significance and helps the physician to select appropriate modes of investigation, to predict the outcome and to choose the treatment of first choice. A delineation of epilepsies based on physiopathologic mechanisms and on etiology remains the ultimate goal. PMID- 8001608 TI - Long-term video-EEG monitoring revisited. The value of interictal and ictal video EEG recording, a follow-up study. AB - Between October 1990 and November 1992, 100 patients were monitored at the University of Gent Epilepsy Monitoring Unit. Sixty-three patients were referred for refractory epilepsy, 38 of whom were entered in the epilepsy surgery protocol. Thirty-seven patients were evaluated for the diagnosis of attacks of uncertain origin. Average duration of monitoring was 3.5 days (2-15 days). Prolonged interictal EEG was recorded in all patients. Ictal EEG was obtained in 63 patients; the average number of recorded episodes was 3 (1-15). Pre-monitoring tentative seizure diagnosis was available in 81 patients, 59 of whom had clinical attacks. Premonitoring diagnosis was confirmed in 31 patients and revised in 28 patients. As a result of the monitoring session, anticonvulsant medication was started in 10 patients, changed in 47, stopped in 5 and left unchanged in 23 patients. Twelve patients underwent surgery. Average follow-up after monitoring was 17 months (4-30 months). Four patients were lost to follow-up; 2 patients died of an underlying disease. In the nonsurgical group (85 patients), 60 patients became seizure-free or experienced significant reduction in seizure frequency. Outcome was unrelated to the availability of ictal recording. While prolonged interictal EEG monitoring is mandatory in the successful management of patients with refractory epilepsy, ictal video-EEG monitoring is very helpful but not indispensable, except in patients enrolled for epilepsy surgery or suspected of having pseudoseizures. PMID- 8001609 TI - Potential gradient of spike and wave temporal foci detected by vertical derivation and neo-electroencephalography. AB - We studied the electrical pattern of spikes and waves and unitemporal foci by compared analysis. One analysis was obtained by two conventional derivations: longitudinal plus triangular and referential to a neck electrode ('vertical derivation'). The other analysis is quantified by the same vertical derivation and by a monopolar-like computerized derivation, the Neo-EEG. With Neo-EEG we obtained a differential dissociation of the spike-and-wave type, and a better analysis of the cerebral dysfunction in temporal foci than in classical EEG. This leads to a sharper diagnosis of the disease it characterizes. This study also shows that one must be aware of the inadequacies and errors resulting from conventional recording because of the bipolar derivations. PMID- 8001610 TI - Somatosensory evoked potentials and jerk-locked EEG back-averaging in myoclonic epilepsy. AB - Median nerve somatosensory evoked potentials (SEPs) and jerk-locked EEG back averaging (JLA) were performed in 2 patients with left-hand myoclonus. Both SEPs were characterized by a normal parietal N20 and an enhanced N27-P27 fronto parietal complex, but the giant central N40 described by most authors was only observed in case 1. Similarily, the aspect of JLA clearly differed in both patients. We hypothetize that both patients exhibited signs of an increased drive of the motor cortex by inputs coming from the sensory cortex. This increased drive could be mediated by the cortico-cortical connexions from areas 1-3 to area 4. In contrast, we suggest that signs of primary hyperexcitability of the motor cortex were only present in case 1, as suggested by the presence of an enhanced N40 in SEPs and the results of JLA studies. PMID- 8001611 TI - Computed tomography and magnetic resonance imaging in epileptic seizures. AB - In epileptic seizures, the sensitivity of CT and MRI depends on different underlying pathologies and varies according to the age of the patient and the type of seizure. The different modalities are discussed in detail. PMID- 8001612 TI - PET and SPECT in epilepsy. AB - Positron emission tomography (PET) measures regional cerebral metabolism and blood flow. PET imaging has been quite successful in identifying focal epileptogenesis as an area of hypometabolism between attacks. PET has proven to be an important diagnostic tool in selecting patients with partial epilepsy, in particular with foci in the temporal lobe, for resective surgery. Because of the high costs and complexities of PET, this technology has been confined to a limited number of centers. Single photon emission computed tomography (SPECT) can also be used for noninvasive functional imaging of the brain because it demonstrates regional cerebral blood flow which is linked to cerebral metabolism. SPECT uses conventional and readily available equipment and radiopharmaceuticals. Emphasizing the outstanding UCLA experience with PET, the presently available data on the usefulness of these functional imaging techniques in the context of surgical treatment of the epilepsies are reviewed. PMID- 8001613 TI - A new type of database of antiepileptic medication for everyday use. AB - AED InfoBase, a first concept for a personal computer based database with an adequate design for everyday use is presented. AED InfoBase operates under a hypertext control program. At present it provides information about pharmacodynamics, pharmacokinetics, side effects and availability of drugs on the market of first choice anticonvulsives. A certain accent is put on drug interactions and drug therapy in epileptics. PMID- 8001614 TI - Type-specific diagnostic analysis of first epileptic seizure in adults. AB - 327 adults patients presenting with a first epileptic seizure were evaluated in respect to underlying causes. The majority suffered from alcohol-related seizures, in the elderly patients vascular pathology dominated. Remote symptomatic seizures raise the question of anticonvulsant therapy. PMID- 8001615 TI - Kappa/lambda ratio as parameter for evaluation of therapy-resistant epilepsy of childhood. AB - In a prospective study we tested the hypothesis whether an alteration in the immunoglobulin light chain kappa and lambda is an expression of an autoimmune mechanism. We investigated 152 children (84 boys, 68 girls, age 12 months to 16 years). Immunoglobulins were analyzed by kinetic nephelometry. The patients were grouped according to clinical and laboratory parameters. A high kappa/lambda ratio caused by high concentration of the kappa-chain was found in children with therapy-resistant epilepsy. 58% showed a high kappa/lambda ratio, in 28% no distinct association was possible and in 14% false-positive results were obtained. In seizure-free children immunological markers were specific in 71%, whilst 25% could not be characterized and 4% showed false-positive results. This alteration of immunoglobulins therefore can be used as a diagnostic parameter. PMID- 8001616 TI - Phenytoin overdosage and cerebellar atrophy in epileptic patients: clinical and MRI findings. AB - Mild overdosage of phenytoin produces reversible cerebellar symptoms (nystagmus, double vision, dysarthria and ataxia). Several case reports suggest that relatively mild and relatively short intoxication can lead to cerebellar degeneration. We observed 11 patients who had episodes of abnormally increased serum levels, most of which developed clinical signs of cerebellar dysfunction. All of these patients were examined with a 1.5-tesla whole-body system (Magnetom, Siemens). Five patients had normal cerebellar structures, although 3 of them had a history of clinical intoxication and all had at least one episode of increased serum level of diphenylhydantoin. The remaining 5 had moderate to severe cerebellar atrophy. Two of them never experienced signs of clinical intoxication. There was no correlation between degree of atrophy and severity of clinical symptoms and elevation of serum DPH levels. There was no correlation between cerebellar atrophy, duration of epilepsy and frequency of seizures. PMID- 8001617 TI - Families and epileptic fits--fit for a family. AB - The author gives a clinical description of an epileptic young girl who consults a psychiatrist in order to assess her troubles of social and school adaptation. Meeting the family makes it possible to single out several critical phenomena. These crises overlap, confusing the questions and the answers medical and psychological competence can suggest. Intergrating the family's resources, the neurologist's skills and the family psychotherapist's proficiency will supply adequate answers as soon as the questions are organized into a coherent system, in which the unknown will nevertheless have its place. PMID- 8001619 TI - Alpha-glucosidase inhibitors in diabetes. Introduction. PMID- 8001618 TI - Influence of lamotrigine addition on computerized background EEG parameters in severe epileptogenic encephalopathies. AB - In 12 adults with typical Lennox-Gastaut syndrome and partial epilepsies with secondary bilateral synchrony unsatisfactorily controlled by current antiepileptic drugs, the following computerized background EEG parameters were studied before and during beneficial antiepileptic effect of lamotrigine addition: absolute and relative spectral power density; alpha/theta index; dominant frequency of occipital alpha, theta and delta bands. The only significant influence of lamotrigine addition was a moderate decrease of the median and mean absolute delta power (p < 0.01). We concluded there was a poor influence of therapeutic doses of lamotrigine on the background diffuse slow dysrhythmias characteristic to severe early encephalopathies which engender both severe secondary epilepsies and different degrees of mental handicap. PMID- 8001620 TI - alpha-Glucosidase inhibitors in diabetes. Proceedings of a workshop. Heidelberg, Germany, 14-17 April 1993. PMID- 8001622 TI - An evaluation of the potential side-effects of alpha-glucosidase inhibitors used for the management of diabetes mellitus. AB - Orally taken alpha-glucosidase inhibitors are used for the management of diabetes mellitus. These drugs can prevent the postprandial rise of the blood glucose level by inhibiting the enzymatic digestion of carbohydrates in the intestinal lumen. Non-absorbable inhibitors such as acarbose are expected to function exclusively in the intestine, but absorbable inhibitors such as miglitol may exert an inhibitory effect on non-intestinal alpha-glucosidases present in the various cell types of the body. The potential side-effects of absorbable inhibitors are evaluated in this literature review. It is concluded that there is little risk of inducing unwanted side-effects when miglitol is taken in an oral dose of approximately 1 mg kg-1 body weight. The use of absorbable inhibitors is, however, not advised in case of kidney dysfunction. PMID- 8001621 TI - alpha-Glucosidase inhibitors in diabetes: lessons from animal studies. AB - Two rat models for non-insulin-dependent diabetes mellitus (NIDDM) have been used in our laboratory to study the effects of alpha-glucosidase inhibitors. These models become hyperglycaemic and have other characteristics which make them good models for NIDDM, and both prevention and reversal studies have been carried out; the prevention experiments were started before the animal became diabetic while the reversal groups were treated after diabetes had fully developed. In both models blood glucose was significantly lowered toward control levels using a dose of 40 mg per 100 g of diet while there was a less dramatic, but still significant, correction with half that dose. Treatment increased the weight gain of the more diabetic model (ZDF) while there was no effect of treatment on the weight of the Wistar diabetic fatty (WDF) rat. Other parameters such as glycated haemoglobins, nerve conduction velocity and nerve sugar content are also reversed with effective treatment of the hyperglycaemic condition. PMID- 8001623 TI - Intestinal effects of alpha-glucosidase inhibitors: absorption of nutrients and enterohormonal changes. AB - The present paper addresses the question how alpha-glucosidase inhibitors affect glucose homeostasis. To facilitate this already established data on the effects of induced malabsorption on gut hormones such as gastric inhibitory polypeptide (GIP) in connection with preliminary findings which deal with the new incretin hormone glucagon-like peptide 1 (7-36) amide (GLP-1) are discussed. To emphasize the possibly important impact of a regulated GLP-1 release in response to glucosidase inhibitor treatment we evaluate the recently introduced concept of 'glucose competence' of pancreatic beta-cells. The slowing of nutrient (i.e. glucose) absorption by therapeutic means (for example, acarbose) could supplement a new approach in the treatment of type 2 diabetics which would utilize the well preserved insulinotropic activity of GLP-1 in these patients, its glucagon lowering effect, and its possible inhibition of gastric emptying rates, the latter helping to reduce the requirement for rapid insulin secretory responses as is intended while using alpha-glucosidase inhibitor treatment. PMID- 8001624 TI - Pharmacology of alpha-glucosidase inhibition. AB - The development of alpha-amylase and brush-border alpha-glucosidase inhibitors is reviewed. The mode of action as well as pharmacological and pharmacodynamic properties of selected inhibitors with special regard to the most thoroughly investigated alpha-glucosidase inhibitor acarbose are discussed. Inhibition of intestinal alpha-glucosidases delays the digestion of starch and sucrose, flattens the postprandial blood glucose excursions, and thus mimics the effects of dieting on hyperglycaemia, hyperinsulinaemia and hypertriglyceridaemia. Therefore, the mechanism of alpha-glucosidase inhibition represents the pharmacological optimization of the dietary principle of delayed carbohydrate absorption. In pre-clinical studies using diabetic animals the oral administration of acarbose improved the metabolic state and reduced the blood glucose area under the curve. As a consequence, the process of non-enzymatic glycation of proteins was retarded as indicated by reduced glycated haemoglobin, glomerular basement membranes or advanced glycation end-products (AGEs) in collagen. These improved biochemical parameters correlated with beneficial effects against the development of diabetic nephropathy and neuropathy. Thus, the treatment of diabetic animals with acarbose does not only improve the metabolic state but has also the potential to delay, or possibly prevent, the development of diabetic complications. PMID- 8001625 TI - alpha-Glucosidase inhibitors in diabetes: efficacy in NIDDM subjects. AB - With alpha-glucosidase inhibitors generally improved metabolic control is achieved in NIDDM patients regardless of whether acarbose is administered in addition to other oral anti-diabetic agents or to diet alone. The most significant finding is the reduction of postprandial blood glucose concentrations. Long-term studies show a decrease in glycosylated haemoglobin and often also in fasting blood glucose levels. Placebo-controlled studies have proven that postprandial insulin concentrations are decreased under acarbose treatment while fasting plasma insulin is usually unchanged. The major side effects of acarbose treatment involve the gastrointestinal system and include flatulence, abdominal discomfort and diarrhoea. Symptoms diminish with treatment time and are less severe when the treatment is started with low doses. Acarbose should usually be initiated as a 50 mg dose immediately before each major carbohydrate containing meal. Monotherapy with acarbose does not cause hypoglycaemia, however, hypoglycaemia may occur with combination of sulphonylurea or insulin treatment by the well-known reasons. In this case hypoglycaemia has to be treated by taking glucose. PMID- 8001627 TI - The use of acarbose in the prevention and treatment of hypoglycaemia. AB - This paper reviews the use of acarbose in the prevention and treatment of hypoglycaemia. In diet- or sulfonylurea-treated patients, acarbose may reduce the incidence of late postprandial hypoglycaemia. In insulin-treated patients, acarbose treatment usually requires reduction of the insulin dose; one study has shown that 100 mg acarbose at night significantly reduces the incidence of mid evening and nocturnal hypoglycaemia. Several studies have suggested acarbose to be a useful adjunct to the management of reactive hypoglycaemia in the non diabetic patients. Long-term prospective studies are still needed to document this last indication of acarbose or other alpha-glycosidase inhibitors. PMID- 8001626 TI - Acarbose and insulin therapy in type I diabetes mellitus. AB - In this paper relevant studies are summarized regarding the use of acarbose as an adjunct to insulin in the treatment of type I diabetes. It is concluded that this approach may contribute to a reduction of postprandial blood glucose excursions and a smoothening of daily blood glucose profiles, an improvement of metabolic control as expressed by glycosylate haemoglobin values and a reduction of insulin requirements. Long-term studies are, however, necessary before one can conclude that addition of acarbose to the therapeutic regimen in type I diabetic subjects is of longstanding value. PMID- 8001628 TI - Efficacy of alpha-glucosidase inhibitors on lipids in NIDDM subjects with moderate hyperlipidaemia. AB - This paper summarizes literature data concerning the action of acarbose, an alpha glucosidase inhibitor, on the concentrations of plasma lipids. Clinical trials in which acarbose has been used in the treatment of non-insulin-dependent diabetics have sometimes shown that it reduces serum triglycerides while it has little or no effect on serum cholesterol levels. The results of a randomized double-blind placebo-controlled study lasting 24 weeks are discussed in more detail. Under the controlled conditions, the effects of acarbose treatment on fasting concentrations of cholesterol, HDL-cholesterol, and triglycerides did not reach statistical significance for the entire patient group. However, in the highest tertile of initial cholesterol concentrations acarbose treatment led to significant lowering of the cholesterol concentration and of the total-to-HDL cholesterol ratio. The most important benefits of acarbose were observed after a test meal given on day 0 and on week 24 of treatment. The triglyceride increment 1 h postprandial was significantly lowered. This was associated by a significant decrease of the insulin increment. Reduction of hyperinsulinaemia appears to be the mechanism by which acarbose treatment can improve plasma lipid concentrations. PMID- 8001629 TI - A new glibenclamide-insensitive neuroselective hyperpolarizing agent. AB - We describe a novel compound, (-)-N-(2-ethoxyphenyl)-N'-(1,2,3-trimethylpropyl)-2 nitroethene-1, 1-diamine), Bay x9227, that demonstrates dose-dependent hyperpolarizing activity of remarkable potency (EC50 3 picomolar) and selectivity for CNS neurons and clonal neurotypic cells compared to smooth muscle cells. Single cell membrane potential measurements were obtained in physiologic buffer using the fluorescent probe, bisoxonol. Unlike K+ATP-channel activators including its (+)-enantiomer (Hoffman et al., 1993, Biochem. Biophys. Res. Commun. 190(2), 551), this activity was insensitive to glibenclamide antagonism. These data suggest a novel pharmacologic site for effecting neuroselective hyperpolarization. PMID- 8001630 TI - Interactive effects of MK-801 and morphine on EEG, EEG power spectra and behavior in rats: I. Morphine tolerance development. AB - This study investigated a potential interaction between MK-801 and morphine tolerance using electroencephalography (EEG), EEG spectral parameters and behavior in the rat. Rats were treated for 7 days with morphine alone or with morphine and MK-801. Control groups received chronic MK-801 alone or saline. On day 8 all rats received morphine alone. Co-treatment significantly accelerated the development of tolerance to morphine-induced total power and latency to sleep onset. Co-treatment, but not morphine alone, produced tolerance to morphine induced complexity and edge frequency, and produced tolerance equal to that from morphine alone in duration of EEG bursting. MK-801 co-treatment decreased, where chronic morphine alone increased, the excitatory response to morphine. Our results support recent reports that chronic morphine treatment produces supersensitivity to glutamate in the rat cortex and alteration in mesolimbic dopamine levels that are modulated by glutamatergic activity. PMID- 8001631 TI - In vitro studies on responses to pentoxifylline and aminophylline of rat mesenteric resistance vessels. AB - Pentoxifylline (1-(5-oxohexyl)-3,7-dimethylxanthine) is a metylxanthine derivative used in the treatment of peripheral arterial disease. In isolated rat mesenteric resistance vessels mounted on an isometric myograph and precontracted with noradrenaline (5 microM), pentoxifylline (0.1 microM-10 mM) and aminophylline (0.1 microM-10 mM) evoked concentration-dependent relaxations. The resistance vessels were more sensitive to pentoxifylline, i.e., the concentration of the agonist evoking 50% relaxation (EC50 value) was 105 +/- 15 microM for pentoxifylline vs. 200 +/- 20 microM for aminophylline (P < 0.01). The vasorelaxant response to pentoxifylline was attenuated by mechanical removal of the endothelium, or by inhibition of the endothelial production of nitric oxide with NG-nitro-L-arginine. Inhibition of cyclooxygenase metabolism with indomethacin did not influence the response to pentoxifylline significantly, but was associated with an increased sensitivity to aminophylline. Furthermore, the vasorelaxation of resistance vessels elicited by pentoxifylline was diminished after incubation with tetraethylammonium, a nonselective K+ channel blocker, and pertussis toxin, an inhibitor of certain G-proteins. In contrast, the vasorelaxation elicited by aminophylline was generally enhanced by these experimental manipulations. The results indicate that the vasorelaxant properties of pentoxifylline and aminophylline in resistance vessels are mediated primarily at the level of the vascular smooth muscle cell, but that the mechanisms of the two agonists partly differ. Endothelial-derived factors (e.g., nitric oxide) contribute to the response to pentoxifylline, and may, through other mechanisms, attenuate the vasorelaxation elicited by aminophylline. PMID- 8001632 TI - Interactive effects of MK-801 and morphine on EEG, EEG power spectra and behavior in rats: II. Morphine dependence. AB - A potential interaction between MK-801 and the cortical electroencephalographic (EEG) and behavioral expressions of morphine dependence in female Sprague-Dawley rats was assessed. Rats were treated chronically (7 days) with either morphine alone, morphine and MK-801, MK-801 alone or saline vehicle alone. On day 8 all rats received morphine alone followed by naloxone. An additional group received chronic (7 days) morphine alone, followed by MK-801 on day 8 prior to morphine and naloxone. Naloxone-induced EEG complexity in morphine-dependent rats was significantly lower than in chronic saline-treated rats. Total power, mobility, mean frequency, complexity and edge frequency in response to naloxone-induced withdrawal in morphine-dependent rats were significantly altered from those in chronically MK-801 alone-treated rats. No differences were found in the EEG and behavioral responses to naloxone between rats that received chronic MK-801 and those that didn't during chronic morphine treatment. Acute MK-801 prior to naloxone in morphine-dependent rats attenuated the behavioral, but not the EEG response to naloxone-induced withdrawal. PMID- 8001633 TI - Reversal of bradykinin-induced relaxation to contraction after interferon-gamma in bovine isolated mesenteric arteries. AB - Bovine isolated mesenteric arterial rings were preincubated for 20 h with interferon-gamma (100 U ml-1) and relaxation in response to bradykinin (10(-12) to 3 x 10(-8) M) was then measured isometrically in an organ bath. Interferon gamma pretreatment for 20 h markedly attenuated the endothelium-dependent bradykinin relaxation in arteries precontracted with 9,11-dideoxy-11 alpha,9 alpha-epoxymethano prostaglandin F2 alpha (U46619), and the relaxation was reversed to contraction at the highest bradykinin concentrations (-72 +/- 5% for control vs. + 6 +/- 10% for interferon-gamma). Cycloheximide (20 micrograms ml-1) present during the 20-h preincubation completely prevented the interferon-gamma effect. Methyl-L-arginine (1 mM) treatment during the 20-h preincubation also inhibited the interferon-gamma effect on bradykinin relaxation (-47 +/- 18% for interferon-gamma and methyl-L-arginine), which suggests involvement of nitric oxide during the 20-h preincubation with interferon-gamma. In control arteries, des-Arg9-bradykinin, a bradykinin B1 receptor agonist, evoked contractions, which were augmented in rings preincubated for 20 h with interferon-gamma. The bradykinin B1 receptor antagonist, des-Arg9-Leu8-bradykinin (2 microM), present in the organ bath in combination with methyl-L-arginine (1 mM) only present during the 20-h preincubation with interferon-gamma completely restored the bradykinin relaxation (-79 +/- 12%). We suggest two mechanisms. Firstly, prolonged nitric oxide release induced by interferon-gamma during the 20-h preincubation may inhibit bradykinin stimulated endothelium-derived nitric oxide release and action. Secondly, interferon-gamma caused upregulation of the bradykinin B1 receptor-mediated contraction, which may contribute to the decrease in bradykinin-induced vasodilation and cause a reversal to contraction. PMID- 8001635 TI - Pharmacological properties of R-84760, a novel kappa-opioid receptor agonist. AB - The pharmacological properties of a structurally novel kappa-opioid receptor agonist, (3R)-3-(1-pyrrolidinylmethyl)-4-[(1S)-5,6-dichloro-1-indancarbo nyl]- tetrahydro-1,4-thiazine hydrochloride (R-84760), were examined. In an opioid receptor binding assay with a guinea pig brain membrane fraction, R-84760 showed a 5 times higher affinity for the kappa-opioid receptor than CI-977, the most potent reference kappa-opioid receptor agonist, and selectivity of R-84760 for the kappa-opioid receptor was higher than that of U-69593, a highly selective kappa-opioid receptor agonist. R-84760 was functionally 2.5 times more potent than CI-977 as a kappa-opioid receptor agonist in rabbit vas deferens. Subcutaneously administered R-84760 had an antinociceptive effect in the phenylquinone writhing test in mice and its potency was 5-846 times higher than those of CI-977, U-50488, morphine, pentazocine and butorphanol. On oral administration, R-84760 was 20-2077 times more potent than the same reference drugs. The antinociceptive effect of R-84760 was not antagonized by naloxone in a dose at which naloxone antagonized the effect of morphine, but on the other hand nor-binaltorphimine antagonized the effect of R-84760 at a dose which did not affect the effect of morphine. R-84760 and the reference kappa-opioid receptor agonists produced sedative and diuretic effects in mice with the same order of potency as for the antinociceptive effect. Tolerance to the antinociceptive effect of R-84760 barely developed, and naloxone-induced jumping tests for morphine-like physical dependence of R-84760 gave negative results. PMID- 8001636 TI - Reversal by imipramine of beta-adrenoceptor up-regulation induced in a chronic mild stress model of depression. AB - Male Wistar rats were subjected to a chronic mild stress procedure involving different stress stimuli applied for 8 weeks. During this time the consumption of 1% sucrose solution was monitored at weekly intervals. After the first 3 weeks, when stressed animals displayed a reduction of sucrose consumption, the control and stressed groups were divided into subgroups receiving daily placebo or imipramine (10 mg/kg/day) treatment. After 5 weeks of treatment, 24 h after the last injection, the rats were killed and beta-adrenoceptor density and affinity in cortical membrane preparations and the accumulation of cyclic AMP in cortical slices stimulated with noradrenaline were assessed. While in stressed placebo treated rats the sucrose consumption remained reduced, in the imipramine-treated group the level of consumption gradually returned to control values. The stressed placebo-treated rats also displayed an increase in cortical beta-adrenoceptor density (by 34%) with no changes in affinity, and an increase (22%) in the cyclic AMP response to noradrenaline in cortical slices. Imipramine, which in non stressed rats did not affect sucrose intake but depressed the beta-adrenoceptor density and the cyclic AMP response, reversed the stress-induced decrease in sucrose consumption and the increase in the beta-adrenoceptor density; at physiological noradrenaline concentrations it also reduced the enhanced cyclic AMP response. The results suggest that the chronic mild stress procedure produces behavioral and biochemical changes consistent with a realistic model of depression in animals. PMID- 8001634 TI - Postjunctional regulation by angiotensin II of alpha 1-adrenoceptor-mediated pressor responses in the rat. AB - The effects of angiotensin II on the vasopressor responses to the selective alpha 1-adrenoceptor agonist, phenylephrine, in intact and sympathectomized rats were investigated. Infusion of angiotensin II at subpressor doses significantly enhanced the pressor effects of phenylephrine in intact rats. We also found that in the chemically sympathectomized rat, where prejunctional sympathetic function is impaired, the effects of angiotensin II infusion on the pressor effects of phenylephrine were similar to those obtained in intact rats. Furthermore, pretreatment with valsartan ((S)-N-valeryl-N-([2'-(1H-tetrazol-5-yl)biphenyl-4 yl]-methyl)-val ine), a new selective angiotensin AT1 receptor antagonist, antagonized the effects of angiotensin II on phenylephrine-mediated pressor responses, whereas the administration of the selective angiotensin AT2 receptor antagonist, PD 123319 (1-[[4-(dimethylamino)-3-methylphenyl]-methyl]-5 (diphenylacetyl)- 4,5,6,7-tetrahydro-1H-imidazo[4,5-c]-pyridine-6-carboxylic acid, ditriflouroacetate, monohydrate), injected in bolus doses of 100 micrograms/kg, did not antagonize the enhancing effect of angiotensin II. Collectively, these data suggest that angiotensin II modulates the response to phenylephrine primarily at a postjunctional level through the activation of angiotensin AT1 receptors and that the suggested prejunctional facilitation mediated by angiotensin receptors is quantitatively much less important in the intact animal. PMID- 8001637 TI - Penile erection and yawning induced by 5-HT1C receptor agonists in male rats: relationship with dopaminergic and oxytocinergic transmission. AB - 1-(3-Chlorophenyl)piperazine (m-CPP) (0.1-4 mg/kg s.c.) and N-(3 trifluoromethylphenyl)-piperazine (TFMPP) (0.5-4 mg/kg s.c.), 5-HT1C receptor agonists, but not 8-hydroxy-dipropylamino-tetralin (8-OH-DPAT) (0.1 and 0.2 mg/kg s.c.), a 5-HT1A receptor agonist, induced penile erection and yawning with a U inverted dose-response curve in male rats. The maximal effect was found with 0.5 mg/kg s.c. of m-CPP and with 1 mg/kg s.c. of TFMPP. The m-CPP (0.5 mg/kg s.c.) and TFMPP (1 mg/kg s.c.) responses were prevented by mianserin (0.2 mg/kg s.c.) and by ritanserin (1 mg/kg s.c.) given 15 min before m-CPP and TFMPP. In contrast, m-CPP- or TFMPP-induced penile erection and yawning were not antagonized by haloperidol (0.1 mg/kg s.c.) or by [d(CH2)5Tyr(Me)2,Orn8]vasotocin (5 micrograms i.c.v.). Apomorphine- and oxytocin-induced penile erection, but not yawning, was also antagonized by mianserin and less effectively by ritanserin. The results suggest that 5-HT1C receptor agonist-induced penile erection and yawning are not mediated by increased dopaminergic and/or oxytocinergic transmission, and raise the possibility that a neuronal dopamine-oxytocin-5-HT link is involved in the control of penile erection and not necessarily of yawning in male rats. PMID- 8001638 TI - Effects of glibenclamide on pancreatic beta-cell proliferation in vivo. AB - Whether hypoglycaemic sulphonylureas promote pancreatic beta-cell replication (beta-cytotrophic action) remains controversial largely because previous studies were based on semi-quantitative techniques only. Here, we used strict quantitative and reliable morphological methods to assess whether glibenclamide affects the replication rate and the mass of beta-cells in normal mice. The animals received a daily intraperitoneal injection of glibenclamide (2 mg/kg body weight) for 7-30 days. Two hours before being killed, they also received an injection of 5-bromo-2'-deoxyuridine, which accumulates in the nucleus of cells in the S-phase of the cell division cycle. Sections of the pancreas were then stained for immunodetection of insulin-containing beta-cells and replicating beta cells (labelled nucleus). The treatment caused a degranulation of beta-cells, an increase in the percentage of beta-cells with a labelled nucleus, but no beta cell hypertrophy. This stimulation of replication led to a small increase in the beta-cell mass at the end of the treatment. However, the effect of glibenclamide on beta-cell replication was short-lasting (less than 15 days) and was observed only when the treatment was started in young animals (23 or 30 days old, but not 42 days old). In conclusion, glibenclamide has a beta-cytotrophic effect which is transient and only seen in young animals. It is unlikely, therefore, that this effect plays a role in the treatment of adult diabetic patients. PMID- 8001639 TI - Differences in relaxant effects of cyclic GMP on skinned muscle preparations from the proximal and distal colon of rats. AB - The relationship between the intracellular cyclic GMP content and relaxation of smooth muscle was studied in preparations from the proximal and distal colon of rats. Nitric oxide increased the cyclic GMP content of longitudinal muscle of both preparations to approximately the same extents. However, although nitric oxide at 0.03-10 microM induced concentration-dependent relaxation of the proximal segments, it did not induce any significant relaxation of the distal segments. The longitudinal muscle preparations were permeabilized by treatment with alpha-toxin to examine the relaxant effects of cyclic GMP on the contractile elements. Ca2+ induced contraction of the permeabilized muscle, the contraction consisting of a transient and subsequent tonic phases. Cyclic GMP (3-100 microM) reversed the tonic contractions induced by various Ca2+ concentrations (1-30 microM). The magnitude of the relaxant effect of cyclic GMP was significantly more in the proximal region than in the distal region. But in contrast to nitric oxide, cyclic GMP induced slight, but clear relaxation of the distal colon. The inhibitory effects of cyclic GMP on phasic contraction, like those on tonic contraction, were high in the proximal region and low in the distal region. These results suggest that the difference in the relaxant effects of nitric oxide in the proximal and distal longitudinal muscles is not due to a difference in extents of cyclic GMP generation, but mainly to a difference in the sensitivities of the contractile elements in the two regions to cyclic GMP. PMID- 8001640 TI - Effect of yohimbine on the contractile response of the mouse vas deferens to short, low frequency trains of nerve impulses. AB - A study was undertaken to ascertain why in the mouse vas deferens excitatory junction potentials facilitate whereas contractions depress during low frequency stimulation. In a set of contraction studies, where a conditioning stimulus was followed 2 s later by a test stimulus, depression in the first phase of contraction was observed only at high stimulus strengths when many nerves are activated leading to a large secretion. Low stimulus strengths did not produce depression, suggesting that the autoinhibitory effect due to released noradrenaline is absent. At supramaximal stimulus strengths short, low frequency (0.1-0.5 Hz) trains gave varying degrees of depression of the first phase at each stimulus frequency. This depression was reversed by yohimbine (10 microM), indicating that the level of autoinhibition depends on the total amount of noradrenaline secreted. In the absence of autoinhibition, facilitation could be predicted in terms of the residual Ca2+ hypothesis. PMID- 8001641 TI - Hypersensitivity to serotonin and its agonists in serotonin-hyperinnervated neostriatum after neonatal dopamine denervation. AB - Neonatal destruction of the nigrostriatal dopamine projection by intraventricular 6-hydroxydopamine leads to a serotonin (5-hydroxytryptamine, 5-HT) hyperinnervation of the adult neostriatum accompanied by increased radioligand binding to 5-HT1B, 5-HT1nonAB and 5-HT2 receptors. The consequences of such 5-HT receptor changes on neuronal responsiveness to 5-HT and corresponding receptor agonists were assessed with a quantitative iontophoretic approach. For comparative purposes, similar data were also obtained from rats 6-hydroxydopamine lesioned as adults, showing severe neostriatal dopamine denervation but no 5-HT hyperinnervation. In controls, 5-HT and its receptor agonists, m chlorophenylpiperazine (mCPP; 5-HT1B/2C agonist) and dimethoxy-iodophenyl aminopropane (DOI; 5-HT2A/2C agonist), depressed the firing rate of a majority of the unit tested. Three months after neonatal 6-hydroxydopamine lesion (5-HT hyperinnervated tissue), inhibitory responses to all three agents were significantly increased and comparable results were obtained for 5-HT and DOI in the rostral versus caudal neostriatum. After 6-hydroxydopamine lesion in adults, neither responsiveness to 5-HT, mCPP or DOI nor the density of 5-HT1B or 5-HT2A binding were significantly different from control. Thus, the up-regulation of 5 HT1B, 5-HT2A and possibly 5-HT2C receptors accompanying the 5-HT hyperinnervation after neonatal but not after adult dopamine denervation was associated with increased responsiveness (IT50) of neostriatal neurons to iontophoresed 5-HT and its receptor agonists. Under these conditions, neostriatal 5-HT transmission might be enhanced in spite of a basal release seemingly comparable to normal (Jackson and Abercrombie, 1992, J. Neurochem. 58, 890).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8001642 TI - Pharmacology of dopamine D3 receptors in the islands of Calleja of the rat using quantitative receptor autoradiography. AB - The pharmacological properties of [3H]7-hydroxy-N,N-di-n-propyl-2- aminotetralin ([3H]7-OH-DPAT) binding sites in the islands of Calleja of the rat were studied using quantitative receptor autoradiography. The KD and the Bmax values of [3H]7 OH-DPAT binding were about 1.6 nM and 100 fmol/mg protein, respectively. The rank order of potency was R(-)-propylnorapomorphine > 7-OH-DPAT approximately haloperidol > raclopride > dopamine > remoxipride. Remoxipride injected in vivo (0.03-100 mumol/kg i.p., 1 h before decapitation) did not inhibit subsequent [3H]7-OH-DPAT binding. These results indicate that the pharmacological profile of dopamine D3 receptors in the islands of Calleja of the rat resembles that obtained from cell lines or membrane preparations. PMID- 8001643 TI - Nitric oxide regulates peptide release from parasympathetic nerves and vascular reactivity to vasoactive intestinal polypeptide in vivo. AB - The possible involvement of nitric oxide (NO) in the vasodilator response to parasympathetic nerve stimulation in the pig submandibular gland in vivo was studied using the NO synthase inhibitor, NG-nitro-L-arginine. The atropine resistant vasodilation elicited by parasympathetic stimulation (10 Hz, 30 s) and the response elicited by i.v. injection of vasoactive intestinal polypeptide (VIP) were markedly reduced by NG-nitro-L-arginine. Furthermore, peptide release from the gland elicited by nerve stimulation was attenuated after NG-nitro-L arginine administration. Addition of the NO donor, nitroprusside, reversed the NG nitro-L-arginine evoked attenuation of the response to nerve stimulation and VIP. Also the cholinergic parasympathetic component and the vascular effect of acetylcholine were reduced by NG-nitro-L-arginine. Furthermore, the NG-nitro-L arginine-induced attenuation of the vascular responses was partially prevented by milrinone, an inhibitor of the cyclic GMP-regulated phosphodiesterase III. The present results suggest that NO may be crucial for parasympathetic vasodilatation by regulating peptide release and second messenger systems for VIP and acetylcholine. PMID- 8001644 TI - DL-propranolol augments production of NO induced by cytokines in cultured aortic smooth muscle of the rat. AB - The effect of DL-propranolol on the production of nitric oxide (NO.) by cultured arterial smooth muscle cells from normotensive (WKY) and spontaneously hypertensive rats (SHR) was studied before and after stimulation by lipopolysaccharide or interleukin-1 beta. The influence of L-arginine and NG nitro-L-arginine on these events was also studied. Lipopolysaccharide-stimulated SHR-derived smooth muscle cells produced less NO. than WKY cells. However the amounts produced in response to interleukin-1 beta were similar for the two cell types. DL-propranolol increased the NO. production in both types of cells exposed to lipopolysaccharide, but had no significant effect on this parameter in WKY derived cells exposed to interleukin-1 beta. Inclusion of L-arginine during incubations with propranolol had no effect on the levels of NO. produced by either cell type exposed to lipopolysaccharide. The basal production of NO. was enhanced in smooth muscle cells from both normotensive and hypertensive rats when the cells were treated with L-arginine after exposure to interleukin-1 beta. L Arginine increased the response to DL-propranolol only in the WKY cells. NO. production was depressed by inclusion of NG-nitro-L-arginine during incubations in both cell types regardless of the treatment regime used to induce NO. synthase activity. The results suggest that DL-propranolol may induce the production of NO. by cultured smooth muscle cells exposed to cytokines. PMID- 8001645 TI - Differential effects of abecarnil on basal release of acetylcholine and dopamine in the rat brain. AB - Abecarnil (0.1-1 mg/kg i.p.), a new anxioselective and anticonvulsant ligand of benzodiazepine receptors, like diazepam (2.5-10 mg/kg i.p.) inhibited in a dose dependent manner the basal release of acetylcholine in the hippocampus of freely moving rats. In contrast, whereas diazepam inhibited the basal output of dopamine in the prefrontal cortex, abecarnil had no such effect. The effects of both abecarnil and diazepam were antagonized by prior treatment with flumazenil at a dose (1 mg/kg i.p.) that per se had no effect on acetylcholine or dopamine release. The results suggest that abecarnil has different intrinsic efficacies at gamma-aminobutyric acid type A (GABAA) receptors involved in the regulation of acetylcholine release in the hippocampus and dopamine release in the prefrontal cortex, two brain areas important in cognitive function and emotional state, respectively. PMID- 8001646 TI - Effect of des-tyrosine-gamma-endorphin on neocortical spike-and-wave spindling in DBA/2J mice. AB - The effect of a beta-endorphin cleavage product devoid of opioid effects, des tyrosine-gamma-endorphin (DT gamma E) on the neocortical spike-and-wave spindling episodes in the electrocorticogram (ECoG) of DBA/2J mice was studied. DT gamma E (0.01-1.0 mg/kg, i.p.) dose dependently reduced the spike-and-wave bursts duration. However, the low dose did not induce consistent modifications of the spike-and-wave bursts number while the dose of 0.1 and 1.0 mg/kg induced a progressive diminution. Furthermore, at all doses DT gamma E did not induce any alterations of the spike-and-wave bursts amplitude, frequency, and desynchronized activity when compared to the pre-drug period. These results indicate that this beta-endorphin fragment may affect brain excitability. PMID- 8001647 TI - Modulation of the delayed rectifier K+ current by apamin in guinea-pig heart. AB - Modulation of the cardiac delayed rectifier K+ current (IK) by apamin was studied in guinea-pig ventricular myocytes using the whole-cell configuration of the patch-clamp technique. Apamin, a peptide toxin isolated from bee venom, is known to inhibit Ca(2+)-activated K+ channel activity. Bath application of apamin prolonged the action potential duration and partially inhibited IK in a concentration-dependent fashion with a half-maximal concentration of 34.4 nM and a Hill coefficient of 1.2. The inhibition of IK occurred at all voltages tested and the block was irreversible. In contrast, the activation curve (P infinity curve) of IK was not shifted by application of apamin, suggesting that the voltage dependence of IK activation is unaffected by apamin. Thus, apamin can partially inhibit cardiac IK without affecting the activation kinetics. This differential sensitivity of IK to apamin suggests that cardiac IK can be separated into two distinct channel populations: the apamin-sensitive K+ channels and the apamin-insensitive K+ channels. PMID- 8001648 TI - Effects of ABT-418, a novel cholinergic channel ligand, on place learning in septal-lesioned rats. AB - Septal lesions disrupt septohippocampal neurotransmission and impair spatial memory. (-)-Nicotine reduces the memory deficits but has substantial side effect liabilities. Previous studies have demonstrated that ABT-418 is a novel, selective ligand for neuronal nicotinic acetylcholine receptors. In the current study, ABT-418 (0.19 and 1.9 mumol/kg, i.p.) administered before training significantly attenuated lesion-induced deficits in a spatial discrimination version of the Morris water maze. As lesion-induced learning deficits might parallel the cognitive deficits characteristic of Alzheimer's disease, these results suggest that ABT-418 may be useful in the treatment of this condition. PMID- 8001649 TI - Analysis of responses to angiotensin IV in the pulmonary vascular bed of the cat. AB - Responses to angiotensin IV were investigated and compared with responses to angiotensin II in the pulmonary vascular bed of the intact-chest cat under constant flow conditions. Under low resting tone conditions, intralobar injections of angiotensin IV caused dose-related increases in lobar arterial pressure. Angiotensin II also increased lobar arterial pressure and was 100 fold more potent than angiotensin IV. Dose-response curves for both peptides were parallel, and the time-to-peak increase in lobar arterial pressure in response to angiotensin IV and angiotensin II was similar whereas the duration of the response to angiotensin IV was significantly shorter. Following administration of the angiotensin receptor subtype 1 (AT1) antagonist, DuP 532 (2-n-butyl-4-chloro 5-hydroxymethyl-1-[(2'-(1H-tetrazol-5-yl)biphe nyl-4- yl)-methyl]imidazole), responses to angiotensin IV and angiotensin II were reduced in a similar manner, whereas pulmonary pressor responses to serotonin were not altered. In contrast to the inhibitory effects of the angiotensin AT1 receptor antagonist, administration of PD 123,319 ((S)-1-[[4-(dimethylamino)-3-methyl-phenyl]methyl-5 (diphenylacetyl++ +)- 4,5,6,7-tetrahydro-1H-imidazol[4,5-c]pyridine-6-carboxylic acid), an angiotensin AT2 receptor antagonist, did not change responses to angiotensin II and angiotensin IV. The results of the present study demonstrate that angiotensin IV has significant vasoconstrictor activity in the pulmonary vascular bed, and suggest that pressor responses to angiotensin IV are mediated by the activation of angiotensin AT1 receptors. These data indicate that angiotensin IV is 100-fold less potent than angiotensin II and suggest that the hexapeptide may have a lower apparent affinity for the angiotensin AT1 receptor than does angiotensin II in the pulmonary vascular bed of the cat. PMID- 8001650 TI - The effect of alpha 2-adrenoceptor antagonists in isolated globally ischemic rat hearts. AB - The alpha 2-adrenoceptor antagonist, yohimbine, has been reported to protect hypoxic myocardium. Yohimbine has several other activities, including 5-HT receptor antagonism, at the concentrations at which protection was found. Therefore we designed a study to determine if yohimbine was protecting ischemic myocardium via antagonism of alpha 2-adrenoceptors. In isolated globally ischemic rat hearts, the effects of two structurally distinct classes of alpha 2 adrenoceptor antagonists, the indole alkaloids (yohimbine and rauwolscine) and the imidazolines (idozoxan and tolazoline) were investigated. Pretreatment with yohimbine (1-10 microM) caused a concentration-dependent increase in reperfusion left ventricular developed pressure and a reduction in end diastolic pressure and lactate dehydrogenase release. The structurally similar compound rauwolscine (10 microM) also protected the ischemic myocardium. In contrast, idozoxan (0.3-10 microM) or tolazoline (10 microM) had no protective effects. The cardioprotective effects of yohimbine were partially reversed by 30 microM 5-HT. These results indicate that the mechanism for the cardioprotective activity of yohimbine may involve 5-HT receptor antagonistic activity. PMID- 8001651 TI - Changes in the responsiveness to endothelin-1 in isolated atria from diabetic rats. AB - This study investigates the influence of diabetes on the cardiac responsiveness to endothelin-1. The effects of endothelin-1 on rate and force of contraction were examined in isolated right and left atria, respectively, obtained from either streptozotocin (65 mg/kg)-treated rats (diabetic) or vehicle (0.02 M citric acid)-treated rats (control). The positive chronotropic and inotropic effects of endothelin-1 did not change in atria from diabetic rats at 2 and 4 weeks, but were reduced at 8 and 12 weeks. The positive chronotropic response to noradrenaline, but not to sympathetic nerve stimulation, was also reduced in 12 week diabetic rats. Endothelin-1 caused a decrease in the positive chronotropic and inotropic responses to sympathetic nerve stimulation and to noradrenaline; these inhibitory effects of endothelin-1 were not altered in 2-, 4-, 8- or 12 week diabetic rats. The study demonstrates that atrial responses to endothelin-1 and to noradrenaline are reduced by streptozotocin-induced diabetes, but the alteration depends on the duration of diabetes. PMID- 8001652 TI - Ameliorating effects of sigma receptor ligands on the impairment of passive avoidance tasks in mice: involvement in the central acetylcholinergic system. AB - Three sigma receptor ligands were examined for their ameliorating effects on p chloroamphetamine-induced amnesia in mice. p-Chloroamphetamine was administered intraperitoneally 30 min before the training session of the passive avoidance response. Each sigma receptor ligand was administered 60 min before or immediately after the training session, or 60 min before the retention test. (+) N-Allylnormetazocine ((+)-SKF-10,047), a prototype benzomorphan sigma receptor ligand, significantly reduced the p-chloroamphetamine-induced amnesia in these three administration schedules, as do acetylcholinesterase inhibitors. On the contrary, the significant anti-amnesic effects elicited by non-benzomorphan sigma receptor ligands, 1,3-di-(2-tolyl)guanidine (DTG) or (+)-3-(3-hydroxyphenyl)-N-(1 propyl)piperizine ((+)-3-PPP), were observed depending upon the timing of their administration. In addition, the ameliorating effect of (+)-SKF-10,047 against the p-chloroamphetamine-induced amnesia was superior to that of (-)-SKF-10,047. The (+)-SKF-10,047-induced anti-amnesic effect was significantly antagonized by the concurrent administration of either scopolamine, a muscarinic receptor antagonist, or hemicholinium-3, an inhibitor of the Na(+)-dependent high-affinity choline uptake site. These findings indicated that sigma receptor ligands had anti-amnesic effects against drug-induced memory impairment. In addition, the anti-amnesic effect of (+)-SKF-10,047 was superior to those of other sigma receptor ligands, and was mediated by both the sigma receptor and the central acetylcholinergic system. PMID- 8001653 TI - Regionally specific changes in extracellular noradrenaline following chronic idazoxan as revealed by in vivo microdialysis. AB - The selective alpha 2-adrenoceptor antagonist idazoxan was administered chronically (0.8 mg/kg per h) to rats for a period of 10 days via osmotic minipumps. On day 11, 24 h after removal of the pumps, the rats were anaesthetised and microdialysis probes were implanted into either the frontal cortex or hippocampus. Basal noradrenaline release in the frontal cortex was significantly elevated compared with the saline control group. Each animal was then challenged with idazoxan (10 mg/kg s.c.). Inhibition of presynaptic alpha 2 adrenoceptors resulted in a significant increase in noradrenaline release in the saline control group. However, animals treated chronically with idazoxan, showed a markedly attenuated response to the single dose idazoxan challenge in the frontal cortex. No significant change in either basal release or in response to idazoxan challenge was observed in the hippocampus in the chronic idazoxan treated animals as compared with the chronic saline control group. Chronic idazoxan administration results in selective enhancement of noradrenaline release in the frontal cortex but not in the hippocampus. This would be consistent with a down-regulation of presynaptic alpha 2-adrenoceptors with the subsequent loss of presynaptic noradrenergic negative feedback inhibition. PMID- 8001654 TI - Alpha 1-adrenoceptor antagonists differentially control serotonin release in the hippocampus and striatum: a microdialysis study. AB - Using the in vivo microdialysis technique, we have studied the effect of the systemic administration of several alpha 1-adrenoceptor antagonists on the extracellular levels of serotonin (5-HT) in the rat hippocampus. Prazosin, and to a lesser extent, terazosin, decreased these levels by 50-65% for 0.03-0.4 mg/kg, i.v. and by 30-40% for 0.1-0.4 mg/kg, i.v., respectively. In contrast, alfuzosin, an alpha 1-adrenoceptor antagonist with poor brain penetration, did not significantly affect these levels even at the high dose of 0.4 mg/kg, i.v. When perfused into the hippocampus through the dialysis probe, prazosin (1-10 microM) induced a more limited (20-30%) and delayed decrease in 5-HT outflow. These results support the existence of a central noradrenergic facilitatory influence, mediated by alpha 1-adrenoceptors, on serotonergic neurons projecting to the hippocampus. In the striatum prazosin (0.4 mg/kg, i.v.) decreased 5-HT levels to a smaller extent (-35%) than in the hippocampus (-65%), suggesting the existence of differences in the degree of noradrenergic influence on median and dorsal raphe nuclei, which preferentially project to the hippocampus and striatum, respectively. PMID- 8001655 TI - Opposite effects of midazolam and beta-carboline-3-carboxylate ethyl ester on the release of dopamine from rat nucleus accumbens measured by in vivo microdialysis. AB - This report describes the effects of midazolam and beta-carboline-3-carboxylate ethyl ester (beta-CCE) on extracellular concentrations of dopamine in the nucleus accumbens of freely moving rats measured by in vivo microdialysis. The two compounds had opposite effects, midazolam (0.075 and 0.15 mg/kg i.v.) dose dependently decreasing, and beta-CCE (3 and 10 mg/kg i.p.) dose dependently increasing, dialysate concentrations of dopamine. Flumazenil (6 micrograms/kg i.v.) did not affect the efflux of dopamine but it prevented the effects of both midazolam and beta-CCE on dopamine efflux. N6-Cyclohexyladenosine (0.1, and 1 mg/kg i.p.), a selective adenosine A1 agonist, dose dependently increased the efflux of dopamine. This effect was blocked by 8-cyclopentyl-1,3-dipropylxanthine (25 mg/kg i.p.), a selective adenosine A1 receptor antagonist, a dose which given alone did not affect dopamine efflux; responses to midazolam were not affected. 3,7-Dimethyl-1-propargylxanthine (1 and 3 mg/kg i.p.), a selective adenosine A2 receptor antagonist, did not mimic the effects of beta-CCE. The results suggest that midazolam and beta-CCE modulate dopamine release in the nucleus accumbens by an action at the benzodiazepine binding site associated with the GABAA receptor complex. PMID- 8001656 TI - The human deferential artery: endothelium-mediated contraction in response to adrenergic stimulation. AB - The human vas deferens receives its blood supply from the deferential artery, a long vessel which usually arises from the superior vesical artery. To date no information is available on the responsiveness of this artery to adrenergic stimulation. In the present work the effects of electrical field stimulation and noradrenaline were studied isometrically in rings of human deferential artery obtained from patients undergoing radical cystectomy (n = 7) or prostatectomy (n = 10). Electrical field stimulation (1-8 Hz, 20 V, 0.25 ms for 30 s) caused frequency-dependent contractions that were abolished by guanethidine, tetrodotoxin or prazosin. Noradrenaline (10(-7)-10(-4) M) induced concentration dependent contractions with an EC50 of 1.3 x 10(-5) M. The increases in tension induced by electrical field stimulation and noradrenaline were of greater magnitude in arteries denuded of endothelium. The inhibitor of nitric oxide synthesis, NG-nitro-L-arginine methyl ester (10(-4) M), potentiated the responses to electrical field stimulation and noradrenaline in artery rings with endothelium. The results indicate that the human deferential artery has a marked ability to contract in response to adrenergic stimulation; they also suggest that the endothelium may have an inhibitory effect on adrenergic responses due, at least in part, to the release of endothelial nitric oxide. These effects could play an important role in regulating blood flow to the vas deferens. PMID- 8001657 TI - Effect of omega-agatoxin-IVA on autonomic neurotransmission. AB - omega-Agatoxin-IVA, a peptide from the venom of the funnel-web spider Agelenopsis aperta and a P type Ca2+ channel inhibitor, was examined for effects on responses to nerve stimulation in isolated autonomic neuroeffector preparations from the rabbit, guinea-pig and rat. Ca(2+)-dependent, tetrodotoxin sensitive, noradrenergic excitatory responses of rabbit pulmonary artery, rat vas deferens, and anococcygeus muscles, and cholinergic guinea-pig myenteric plexus preparations (all highly sensitive to the N type Ca2+ channel inhibitor omega conotoxin-GVIA) were unaffected by omega-agatoxin-IVA (100 nM). Similarly, the neurogenic response of rat bladder, which has cholinergic, and non-adrenergic non cholinergic (NANC) excitatory components, and the NANC inhibitory response of rat jejunum (atropine 0.5 microM- and guanethidine 5.0 microM-treated), which are partially sensitive and insensitive to omega-conotoxin-GVIA, respectively, were unaffected by omega-agatoxin-IVA (100 nM). Neurogenic NANC inhibitory responses of the guinea-pig taenia caecum, and rat anococcygeus muscles (atropine- and guanethidine-treated, and tone raised with prostaglandin F2 alpha), were also insensitive to omega-agatoxin-IVA. These results suggest that P type Ca2+ channels, if present, play an insignificant role in supplying the Ca2+ necessary for neurotransmitter release in the peripheral autonomic nervous system. PMID- 8001658 TI - Binding properties of KB-5492, a novel anti-ulcer agent, at sigma receptors in porcine gastric fundic mucosa. AB - We examined the effects of KB-5492, 4-methoxyphenyl 4-(3,4,5-trimethoxybenzyl)-1 piperazine acetate monofumarate monohydrate, a novel anti-ulcer agent and a selective sigma receptor ligand, on specific [3H](+)-N-allyl-normetazocine (SKF 10,047) and [3H]1,3-di(2-tolyl)guanidine (DTG) binding in porcine gastric fundic mucosa. KB-5492 inhibited specific [3H](+)-SKF 10,047 binding in a competitive manner and specific [3H]DTG binding in a non-competitive manner. The Ki value of KB-5492 on specific [3H]DTG binding (Ki = 4.6 microM) was 8.4-fold higher than that on specific [3H](+)-SKF 10,047 binding (Ki = 0.55 microM). Computer-assisted analysis of the displacement curve of KB-5492 for specific [3H]DTG binding indicated the best fit for a two-site model rather than a one-site model, but not for specific [3H](+)-SKF 10,047 binding. Anti-ulcer agents such as omeprazole, cetraxate, cimetidine, sofalcone, sucralfate, teprenone and troxipide had weak or little effect on specific [3H](+)-SKF 10,047 and [3H]DTG binding at a concentration of 100 microM, except that omeprazole exhibited a low affinity for specific [3H](+)-SKF 10,047 binding. These findings suggest that KB-5492 is a unique anti-ulcer agent which binds to sigma receptors in porcine gastric fundic mucosa. PMID- 8001659 TI - Antagonism between T3 and amiodarone on the contractility and the density of beta adrenoceptors of chicken cardiac myocytes. AB - 3,3',5-Triiodothyronine (T3), at 10(-8) M, potentiated by 26.4-30.9% the isoproterenol-mediated inotropic effect in chick embryo cardiac myocytes in culture. Amiodarone (10(-6) M) decreased this response by 44.6% only in cells cultured with serum, where the T3 concentration was 10(-13) M. Amiodarone inhibited the potentiating effect of T3. Amiodarone alone had no influence on the beta-adrenoceptor density in cells cultured in serum-free medium. This confirms that the effects of amiodarone on cardiac beta-adrenoceptors are T3 dependent. T3 increased the density of beta-adrenoceptors through two concentration ranges, with an initial 30% increase between 10(-14) and 10(-11) M, followed by a second increase until 10(-7) M. Amiodarone not only inhibited the first positive effect of T3 but also decreased beta-adrenoceptor density far below the control value. The second positive T3 effect was also inhibited by 50% by amiodarone. This study suggests that T3 might increase the number of cell-surface beta-adrenoceptors and modify their cellular traffic through at least two mechanisms, one assumed to be non-genomic, the other being genomic, and that amiodarone could affect the two mechanisms differently. PMID- 8001660 TI - Brugia malayi: the diagnostic potential of recombinant excretory/secretory antigens. AB - The diagnostic potential of recombinant E/S antigens of the lymphatic filaria Brugia malayi was investigated by Western blot. A cDNA expression library was constructed using B. malayi male adult worm mRNA, and E/S recombinants were identified with a rabbit antiserum raised against E/S products collected in vitro from B. malayi male and female adult worms. Two of these recombinants, Bm12 and Bm14L, were studied after subcloning the cDNA inserts in an Escherichia coli plasmid expression and purification vector, obtaining the inserts' nucleotide sequence, and purifying the expressed proteins. By homology of their deduced amino acid sequence with that of previously identified proteins, Bm12 was identified as the B. malayi gp 15/400 antigen, and Bm14 as a member of the hsp90 family of heat shock proteins. The antigenic cross-reactivity of the purified recombinant proteins was assessed with 28 serum samples from patients infected with Ascaris, Trichuris, or hookworm, and also with a few samples from patients with onchocerciasis and loiasis. For Bm12, the specificity for all of the intestinal helminthiasis together was 75%. Bm14L, on the other hand, cross reacted with all of the ascariasis serum samples with which it was tested. Presence of antibodies cross-reactive with B. malayi was confirmed in all of these serum samples by examining their antibody reactivity with Western blots of extracts of whole B. malayi adult worms. A semiquantitative (+ or -) assessment of the sensitivity of Bm12 for antibody detection was performed using 6 serum samples from patients with chronic filariasis and 24 samples from patients with microfilaremia. All of these serum samples contained anti-Bm12 antibody (sensitivity of 100%). Finally, the ability of Bm12 to detect antibody before the onset of patency was established with a longitudinal collection of serum samples obtained from 2 African green vervets (Cercopithecus aethiops) and 3 rhesus macaques (Macaca mulatta), all of which were infected with B. malayi. Anti-Bm12 antibodies were detectable in all animals between 4 and 11 weeks before patency. PMID- 8001661 TI - Plasmodium falciparum: a family of sulphated glycoconjugates disrupts erythrocyte rosettes. AB - The ability of Plasmodium falciparum-infected erythrocytes to form spontaneous rosettes with uninfected red cells is a parasite adhesion property which has been associated with severe malaria. The mechanism of rosetting remains unknown, but the ability of heparin to disrupt rosettes has been recognised previously. In this paper we show that a group of sulphated glycoconjugates including sulphatide, dextran sulphate, and fucoidan are more effective rosette reversing agents than heparin and are active against both laboratory strains and wild isolates. Other related anionic glycosaminoglycans such as the chondroitin sulphates A, B, and C and hyaluronic acid have no effect on rosette formation. This family of sulphated glycoconjugates which are active against rosettes is also known to inhibit sporozoite invasion of hepatocytes and merozoite reinvasion of erythrocytes, suggesting that sulphated glycoconjugate interaction may be an important process in cell adhesion at different stages in the plasmodial life cycle. PMID- 8001662 TI - Plasmodium falciparum: selective growth of subpopulations from field samples following in vitro culture, as detected by the polymerase chain reaction. AB - Analysis of the Plasmodium falciparum parasites circulating in the blood of infected persons frequently reveals the presence of two or more genetically distinct parasite populations. P. falciparum parasites cultured in vitro, from blood specimens collected in the field, are often used for biological, immunological, and drug-resistance investigations relating to the epidemiology in the area concerned or on the assumption that the parasites which grow in vitro are in general representative of all P. falciparum parasites. By using the polymerase chain reaction to detect and characterize a number of parasite polymorphic genes with great sensitivity, the composition of P. falciparum populations from 51 isolates were compared on the day of collection and following 2 months of in vitro culture. It was found that substantial changes in the parasite population profile could be detected in ca. 70% of the samples analyzed. The implications of this observation for studies using parasite isolates cultured in vitro are discussed. PMID- 8001663 TI - Angiostrongylus cantonensis: characterization of thymidylate synthetase. AB - Thymidylate synthetase (TS) is the only enzyme that catalyzes the formation of thymidine nucleotides in Angiostrongylus cantonensis. A fraction enriched in TS was obtained from the gravid nematode by gel filtration and affinity chromatography using methotrexate-agarose. TS, which was well separated from dihydrofolate reductase, has a relative molecular mass of 66 kDa. By electrophoresis in sodium dodecyl sulphate gel, a major protein band corresponding to 31 kDa was observed. This band was shown to be TS by comparing the electrophoretic mobility with an enzyme preparation bound with [6-3H]5-fluoro 2'-deoxyuridine 5'-monophosphate (FdUMP). Therefore, the enzyme is composed of two identical or very similar subunits. Velocity studies and product inhibition patterns revealed that the TS reaction undergoes a sequential mechanism in which 2'-deoxyuridine 5'-monophosphate (dUMP) is the first substrate added to the active site and thymidine 5'-monophosphate is the last product released. The apparent Km values for dUMP and 5,10-methylenetetrahydrofolate are 10 and 185 microM, respectively. FdUMP and trimethoprim inhibited the parasite TS competitively with dUMP and the Ki values of 23.5 nM and 852 microM, respectively. Methotrexate was a noncompetitive inhibitor of TS. At 0.2 mM 5,10 methylenetetrafolate, 1 mM methotrexate inhibited the activity by 74%. PMID- 8001665 TI - Codon usage in the double-stranded RNA viruses of Giardia and Leishmania. PMID- 8001664 TI - Trypanosoma cruzi: immunolocalization of trypanothione reductase. PMID- 8001666 TI - Evidence for and implications of anti-embryonation immunity in schistosomiasis. PMID- 8001667 TI - Suppression of antiproliferative effects of tumor necrosis factor by transfection of cells with human platelet-derived growth factor B/c-sis gene. AB - The growth of cells is determined by the balance between growth-stimulatory and growth-inhibitory signals. In the present study, we demonstrate that the transfection of NIH 3T3 cells with a platelet-derived growth factor (PDGF-Blc sis) gene induces resistance to the anticellular effects of tumor necrosis factor (TNF). Human tumor cell lines that express elevated levels of c-sis (e.g. epidermoid carcinoma, A-431) are also TNF resistant, whereas those that express no significant levels of this gene (e.g. breast adenocarcinoma, MCF-7) are TNF sensitive. Transfection of cells with the c-sis gene leads to down-modulation of TNF receptors and also a decrease in intracellular glutathione levels. Thus, our results demonstrate that over-expression of PDGF-Blc-sis by certain tumor cells can lead to their protection from the anticellular effects of TNF. PMID- 8001668 TI - Pilins of fimbrial adhesins of different member species of Enterobacteriaceae are structurally similar to the C-terminal half of adhesin proteins. AB - The structural relatedness of pilins and the C-terminal half of adhesin proteins in different member species of Enterobacteriaceae was deduced from their two dimensional sequence analysis using the hydrophobic cluster analysis (HCA) and secondary structure predictions from the profile network Hei-Delberg program (PHD). Despite a large evolutionary distance between the two protein families, we show that pilins and the C-terminal domain of adhesins have a similar folding that can serve as modules for pilus assembly. PMID- 8001670 TI - Phosphate regulation of biosynthesis of extracellular RNases of endospore-forming bacteria. AB - The gene for the extracellular ribonuclease of B. pumilus KMM62 (RNase Bp) has been cloned and sequenced. The structural gene for this enzyme is similar to those of the extracellular ribonucleases of B. intermedius 7P (binase) and B. amyloliquefaciens H2 (barnase), as are the regulatory regions of binase and RNase Bp. The regulatory region of the barnase gene, however, is quite different from the other two. In the promoter of the genes for binase and RNase Bp, but not in that for barnase, is a region similar to the Pho box of E. coli. We have established that inorganic phosphate suppresses the synthesis of the binase and RNase Bp, but does not effect the synthesis of barnase. PMID- 8001669 TI - Effect of transmembrane Ca2+ gradient on Gs function. AB - Gs and adenylate cyclase from bovine brain cortices were co-reconstituted into asolectin liposomes with or without 1000-fold transmembrane Ca2+ gradient. Obtained results showed that Gs activities of both binding GTP gamma S and stimulating adenylate cyclase were the highest in proteoliposomes, with a transmembrane Ca2+ gradient similar to the physiological situation and the lowest while the transmembrane Ca2+ gradient was in the inverse direction. Such a difference could be diminished following the dissipation of the transmembrane Ca2+ gradient by A23187. Time-resolved fluorescence anisotropy of diphenylhexatriene (DPH) has been used to compare the physical state of phospholipids among those proteoliposomes. It is suggested that a proper transmembrane Ca2+ gradient is essential for higher membrane fluidity, which may favor Gs function with higher GTP-binding activity and stimulation of adenylate cyclase. PMID- 8001672 TI - Expression of the mouse and rat mas proto-oncogene in the brain and peripheral tissues. AB - We isolated the mas proto-oncogene from a mouse genomic library. Sequence analysis showed that it contains an open reading frame without intervening sequences. The amino acid sequence deduced confirms the seven-transmembrane domain structure and exhibits 97% and 91% amino acid homology with the rat and the human Mas, respectively. In mice and rats, mas mRNA was detected in the testis, kidney, heart, and in the brain regions: hippocampus, forebrain, piriform cortex, and olfactory bulb. Testicular mas mRNA from rats increases markedly during development, while cerebellar mRNA is high postnatally but completely disappears at later stages. We conclude that the product of the mouse mas gene may be involved in the development of the brain and testis. PMID- 8001671 TI - Two GTPs are consumed on EF-Tu per peptide bond in poly(Phe) synthesis, in spite of switching stoichiometry of the EF-Tu.aminoacyl-tRNA complex with temperature. AB - Recent observations indicate that the stoichiometry for the complex between EF Tu.GTP and aminoacyl-tRNA (aa-tRNA) changes with temperature. At 37 degrees C two EF-Tu.GTPs bind one aa-tRNA in an extended ternary complex, but at 0 degrees C the complex has 1:1 stoichiometry. However, the present experiments show that there are two GTPs hydrolyzed on EF-Tu per peptide bond in poly(Phe) synthesis at 37 degrees C as well as at 0 degrees C. This indicates two different pathways for the enzymatic binding of aa-tRNA to the A-site on the ribosome. PMID- 8001673 TI - Tissue inhibitor of metalloproteinases-2 (TIMP-2) in rat liver cells is increased by lipopolysaccharide and prostaglandin E2. AB - To explore the functional role of TIMP-2 in liver, we determined TIMP-2 mRNA levels in primary rat hepatocytes and in total rat liver. Rat hepatocytes constitutively express TIMP-2 mRNA at a low level. Incubation with dexamethasone, prostaglandin E2 and a combination of inflammatory cytokines leads to an up regulation of TIMP-2 mRNA. In rats in vivo we found a dramatic increase of TIMP-2 expression after intraperitoneal injection of lipopolysaccharide. Compared to our previous findings on TIMP-1 we conclude that TIMP-2 mRNA expression is regulated in a distinct and partially opposite manner. Over-production of TIMP-2 could inhibit the activity of metalloproteinases and thus lead to matrix accumulation. Dysregulation of TIMP-2 synthesis might be involved in the development of liver fibrosis. PMID- 8001674 TI - The conformational flexibility of 5,6,7,8-tetrahydrobiopterin and 5,6,7,8 tetrahydroneopterin: a molecular dynamical simulation. AB - 5,6,7,8-Tetrahydrobiopterin is an essential cofactor of diverse enzymes. Of the eight possible stereoisomers, only the 6R,1'R,2'S-configuration is biologically active. Other stereoisomers, as well as other reduced pterins such as, e.g. 5,6,7,8-tetrahydroneopterin, fail to exhibit significant cofactor activity. Different theoretical models (molecular mechanics, semi-empirical quantum chemical calculations) investigating the stereostructure of tetrahydrobiopterin have yielded diverging answers. It has been claimed on the basis of semi empirical quantum chemical calculations that conformational properties, and thus particular features in overall shape, might be responsible for the unique biological properties of natural tetrahydrobiopterin in contrast, e.g. to 6R,1'S,2'R-5,6,7,8-tetrahydroneopterin. Molecular dynamical simulations of both molecules at realistic temperatures demonstrate, however, that they possess sufficient conformational flexibility as to render questionable any biological significance of mere conformational properties. PMID- 8001675 TI - N-acetyl-L-cysteine inhibits antigen-mediated Syk, but not Lyn tyrosine kinase activation in mast cells. AB - High affinity IgE receptors (alpha beta gamma 2) mediate the activation of the non-receptor tyrosine kinases Lyn and Syk. Here we show that the antioxidant drug N-acetyl-L-cysteine (NAC) inhibits antigen-mediated Syk activation whereas Lyn activation and phosphorylation of beta and gamma is maintained. Furthermore, NAC inhibits antigen-mediated calcium mobilization and exocytosis in a dose-dependent manner, but does not inhibit ionomycin-induced exocytosis. These data support a model in which the activation of Lyn is responsible for receptor phosphorylation and precedes the activation of Syk. The inhibition of Syk activation by NAC may be relevant to B and T cell antigen receptors, which are also linked to Syk/ZAP70 tyrosine kinases. PMID- 8001676 TI - Transcriptional repression mediated by the serum response factor. AB - The serum response element (SRE) contributes to transcriptional repression of the c-fos proto-oncogene. We show that the transcription factor SRF is able to repress SRE-dependent transcription, apparently by sequestering a co-activator. Only the DNA-binding core region is required for this SRE-dependent repression. Furthermore the phosphorylation status at potential casein kinase II sites within an N-terminal repression domain affects SRE-independent transcription. SRF may thus pleiotropically influence cellular transcription, representing a novel aspect of SRF function. PMID- 8001677 TI - Characterisation of the single copy trefoil peptides intestinal trefoil factor and pS2 and their ability to form covalent dimers. AB - A bacterial recombinant expression system was established to produce biologically active rat Intestinal Trefoil Factor (rITF). Characterisation of purified rITF shows that both monomers and dimers can be observed under reducing and non reducing conditions, respectively. Site-directed mutagenesis studies show that Cys57 is necessary for rITF dimer formation. Samples of human gastrointestinal tissue following biopsy also demonstrated the presence of reducible human pS2 and ITF covalent dimers. Three-dimensional models for pS2 and ITF support the hypothesis that both pS2 and ITF can exist as disulphide-linked dimers in vivo and that any proposed function for these peptides must take dimer formation into account. PMID- 8001678 TI - Photoreduction of silicomolybdate in chloroplasts by agents accelerating the deactivation reactions of the water-oxidizing system. AB - Uncouplers of photosynthetic phosphorylation, CCCP, TTFB and PCP, inhibited light induced O2 evolution in the Hill reaction with SiMo (I50 approximately 20, 3 and 45 microM, respectively), but only insignificantly diminished SiMo photoreduction by pea chloroplasts. The same properties were exhibited by the ADRY agent ANT2p. CCCP, TTFB and PCP are oxidizable compounds with redox potentials of +1.17, +1.18 and +1.09 V (pH 6.0), as determined by cyclic voltammetry. Similarly to NH2OH, the tested uncouplers can apparently serve as electron donors for photosystem II. PMID- 8001679 TI - Heat denaturation of pepsinogen in a water-ethanol mixture. AB - The effect of ethanol and pH on thermodynamic parameters and cooperativity of pepsinogen heat denaturation was studied by scanning microcalorimetry. Addition of 20% ethanol decreases the protein denaturation temperature by 10.7 degrees C at pH 6.4 and 15.8 degrees C at pH 8.0. It also decreases the denaturation heat capacity increment from 5.8 to 4.2 kcal/K.mol. The dependences of calorimetric denaturation enthalpy on denaturation temperature both in water and 20% ethanol are linear and intersect at about 95 degrees C. In 20% ethanol the pH shift from 5.9 to 8.0 results in a decreased number of cooperative domains in pepsinogen. This process causes no changes either in the secondary structure or in the local surroundings of aromatic amino acids. It is concluded that ethanol addition does not affect the cooperativity of pepsinogen denaturation substantially until the pH change provokes redistribution of charges in the protein molecule. PMID- 8001680 TI - Crystallization and preliminary crystallographic studies of recombinant dimerization cofactor of transcription factor HNF1/pterin-4 alpha-carbinolamine dehydratase from liver. AB - The bi-functional protein dimerization cofactor of HNF1 (DCoH)/pterin-4 alpha carbinolamine dehydratase (PCD) is found in liver cell nuclei bound to the transcription factor hepatocyte nuclear factor 1 (HNF1) as well as in the cytoplasm acting as an enzyme involved in the phenylalanine hydroxylation system. Deficiency of DCoH/PCD activity in liver causes an atypical hyperphenylalaninemia and deficiency in human epidermis is related to the depigmentation disorder vitiligo. DCoH/PCD from rat liver, which is identical to the human protein, was expressed in E. coli, purified to homogeneity and crystallized. The crystals belong to the trigonal space group P3(1)21 (or P3(2)21) with unit cell dimensions of a = b = 106.2 A, c = 197.1 A. Native crystals diffract to a resolution of 2.5 A. PMID- 8001681 TI - MALDI-MS for C-terminal sequence determination of peptides and proteins degraded by carboxypeptidase Y and P. AB - Matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS) has been used for C-terminal amino acid sequence determination of peptides and proteins. The usefulness of MALDI-MS was demonstrated by analyzing peptide mixtures (C terminal peptide ladder) which were generated by enzymatic digestion of substance P, glucagon, angiotensinogen, insulin B chain and myoglobin with the exopeptidases carboxypeptidase Y and P. The results clearly show that up to 11 amino acid residues can be determined in the pmol range by analyzing the molecular masses of the truncated peptides. For proteins it is possible to investigate enzymatic or chemical digests in the same manner. PMID- 8001682 TI - Susceptibility of phospholipids of oxidizing LDL to enzymatic hydrolysis modulates uptake by P388D1 macrophage-like cells. AB - Addition of the phospholipids 1-O-hexadecyl-2-arachidonoyl-sn-glycero-3 phosphocholine (PLE) and 1-O-hexa-decyl-2-desoxy-2-amino-arachidonyl-sn-glycero-3 phosphocholine (PLA) to [125I]LDL and subsequent Cu(2+)-induced oxidation result in significant differences in protein modification and uptake by P388D1 macrophage-like cells. PLE-treated LDL is ingested at a 1.27-fold rate compared to PLE-treated LDL and displays enhanced electrophilic mobility. Similar results (1.43-fold enhanced uptake of LDL preloaded with PLE) are obtained when the uptake of phospholipid-enriched oxLDL particles are examined. The preference for ingestion as well as protein modification of both preparations is, however, reversed under experimental conditions allowing diffusion and inactivation of a fraction of the peroxidation products. These findings suggest that LDL-associated PAF-acetylhydrolase can exert a dual role and, to be protective to LDL, require an appropriate microenvironment, capable of binding certain species of oxidatively fragmented lipids. PMID- 8001683 TI - The high potential iron-sulfur protein (HiPIP) from Rhodoferax fermentans is competent in photosynthetic electron transfer. AB - The functional role of the High Potential Iron-sulfur Protein (HiPIP) from the photosynthetic bacterium Rhodoferax fermentans was investigated. We demonstrated that the HiPIP increased the rate of light-induced oxygen reduction mediated by the photosynthetic reaction center (RC); this stimulation reached half-saturation at [HiPIP]/[RC] ca. 15. The capability of the HiPIP in delivering electrons to the reaction center of Rhodoferax fermentans was demonstrated through kinetic spectrophotometry of cytochrome c-556 oxidation in the presence or in the absence of HiPIP. It is concluded that the HiPIP is competent in the photosynthetic electron transfer chain of Rhodoferax fermentans. PMID- 8001684 TI - Differential penetration of fatty acyl-coenzyme A and fatty acylcarnitines into phospholipid monolayers. AB - The ability of fatty acyl-CoA's and fatty acylcarnitines to penetrate phospholipid monolayers was comparatively studied, in view of the important role of both kinds of derivatives in fatty acid transport across mitochondrial membranes. The interaction occurs predominantly through hydrophobic forces. Acylcarnitines penetrate phospholipid monolayers more strongly than acyl-CoAs; in addition the former show a positive cooperativity when they bind to the interface. These properties would facilitate membrane transfer of fatty acylcarnitines over that of their CoA homologues. PMID- 8001685 TI - Purification and characterization of an iron superoxide dismutase from the nitrogen-fixing Azotobacter vinelandii. AB - Two electrophoretically distinct forms of superoxide dismutase (SOD; EC 1.15.1.1) which show different inhibition patterns to hydrogen peroxide have been identified in Azotobacter vinelandii. The SOD inhibited by hydrogen peroxide was purified to homogeneity, and turned out to be an iron superoxide dismutase. The enzyme is present in only one molecular form with an isoelectric point of 4.1, and it is composed of two identical subunits with an apparent molecular weight of 21,000 Da. Spectroscopic analyses indicated that this enzyme contains ferric iron (1.4-1.6 mol/mol protein) in the typical high-spin form present in other prokaryotic Fe-SODs. N-Terminal sequence alignments (up to the 49th residue) showed that A. vinelandii Fe-SOD has high similarity with other prokaryotic Fe SODs. PMID- 8001686 TI - The widely used anesthetic agent propofol can replace alpha-tocopherol as an antioxidant. AB - The cell membrane is protected against lipid peroxidation through endogenous antioxidants such as the lipid soluble alpha-tocopherol. The anesthetic agent propofol (2,6-diisopropylphenol) has a chemical structure which is similar to alpha-tocopherol, since it also contains a phenolic OH-group. The transient protection of GSH against lipid peroxidation in control liver microsomes is not observed in microsomes deficient in alpha-tocopherol. Introducing propofol (2 and 5 microM) restored the protective effect of GSH. Similar to the control microsomes the GSH-protective effect did not occur in previously heated microsomes. These results suggest that propofol acts similarly to alpha tocopherol as a chain breaking antioxidant in liver microsomal membranes. PMID- 8001688 TI - DAMGO, a mu-opioid receptor selective agonist, distinguishes between mu- and delta-opioid receptors around their first extracellular loops. AB - The structural basis of mu-opioid receptor (OPR) for the specificity in its ligand binding was investigated using chimeric mu/delta-OPRs. Replacement of the region around the first extracellular loop of delta-OPR with the corresponding region of mu-OPR gave the resultant chimeric receptor the similar affinity to DAMGO compared with the native mu-OPR. The reciprocal replacement deprived the high affinity to DAMGO from mu-OPR. These results indicate that the difference(s) in the structure around the first extracellular loop is critical for DAMGO to distinguish between mu- and delta-OPRs. Furthermore, displacement studies revealed that this region is partly involved in the discrimination between mu- and delta-OPRs by other peptidic mu-selective ligands, such as dermorphin, morphiceptin and CTOP, but not by non-peptidic ligands, such as morphine and naloxone. PMID- 8001687 TI - Molecular cloning of an orphan transporter. A new member of the neurotransmitter transporter family. AB - A complementary DNA clone predicted to encode a novel transporter was isolated from rat brain and the localization of its mRNA was examined. The cDNA, designated rB21a, predicts a protein with 12 putative transmembrane domains that exhibits significant sequence homology with neurotransmitter transporters. Expression studies have not yet identified the endogenous substrate for this transporter, but the presence of rB21a mRNA within the leptomeninges of the brain suggests the transporter may regulate CSF levels of its substrate. The cloning of rB21a provides the means to determine its physiological functions and the potential to design novel, transporter-based therapeutic agents for neurological and psychiatric disorders. PMID- 8001689 TI - A 70 kDa protein is transferred from the outer acrosomal to the plasma membrane during capacitation. AB - Bull sperm plasma and outer acrosomal membranes were analyzed by SDS-PAGE. Analysis of the plasma membrane proteins revealed the presence of a 70 kDa band the prominence of which is enhanced after capacitation. This protein was found to bind to zona pellucida intact oocytes. PAGE analysis of outer acrosomal membrane proteins also reveals the presence of a 70 kDa band, but its prominence decreases after capacitation. This protein also binds to zona pellucida intact oocytes. Furthermore, the 70 kDa outer acrosomal membrane protein is recognized in Western blot analysis by antibodies to plasma membrane proteins and vice versa. The results indicate that the 70 kDa acrosomal and plasma membrane proteins are the same. This 70 kDa protein would thus be a zona pellucida binding protein which is initially stored in the outer acrosomal membrane and transferred to the plasma membrane during capacitation, enabling it to function in egg-sperm binding. PMID- 8001690 TI - [Analysis of neuropeptide release by brain microdialysis]. AB - The application of the microdialysis technique for the analysis of neuropeptide release was described. The recoveries of neuropeptides are affected by the nature of the dialysis membrane, the sort of perfusion method, the internal diameter and length of the outlet tube, and the flow rate of the perfusate. The studies on the mechanism of neuropeptide release using brain microdialysis were summarized. Brain microdialysis technique allows the direct and dynamic analysis of neuropeptide release and provides a useful tool for studying the mechanism of the central regulation of the release of neuropeptides. PMID- 8001691 TI - [Endocrinological and imaging analyses of adrenal incidentalomas with hypertension and/or diabetes mellitus]. AB - Adrenal tumors showing no clinical manifestations (incidentaloma) are frequently encountered during imaging analysis upon routine examinations. These tumors are sometimes associated with hypertension and/or diabetes mellitus (DM). We have examined six cases of incidentalomas with these symptoms in this study. All patients underwent endocrinological evaluation by measuring plasma cortisol and aldosterone levels to assess adrenocortical function. The levels of urinary 17 hydroxysteroids, 17-ketosteroids and catecholamines were also measured. Imaging analysis were performed by using 131I-adosterol scintigraphy, computed tomography and magnetic resonance imaging. Whereas one case was diagnosed as having an adrenal adenoma without the examination of a surgical specimen, other cases underwent surgical removal of the tumor, and final diagnoses were made by pathohistological examination of the tumors. Three cases were diagnosed as having adrenocortical adenomas (one was functioning and others were non-functioning) and one case was diagnosed as having a functional adrenocortical carcinoma. Adenomas were found to produce either non-functional steroids or a small amount of functional steroid hormones. The adenoma patients all suffered hypertension, whereas one of the adenoma patients and the carcinoma patient showed signs of DM. By contrast, of the six cases, one case was diagnosed as having an adrenal cyst, and one case was diagnosed with myelolipoma. Although these two cases suffered DM and hypertension, respectively, it seemed to be unlikely that these clinical symptoms were caused by the adrenal disease. Thus, the present analysis of the six incidentaloma patients suggests that once an adrenal incidentaloma patient with hypertension and/or DM is found, both endocrinological and imaging examinations are necessary to determine the indication of surgical treatment. This analysis supports the present consensus that non-functional adenomas whose sizes are 3cm or less and whose sizes do not change at any reevaluation period, as well as adrenal cysts and myelolipoma should not be surgically removed. PMID- 8001692 TI - [A case report of primary triple cancers in the thyroid, stomach and rectum with evidence of variable oncoprotein expressions]. AB - A case with primary triple cancers including thyroid cancer is reported. A 57 year old woman complaining of laryngeal discomfort was found to have an firm elastic lump on the right anterior neck. On 123I scan, the nodule in the right thyroid lobe accumulated considerable amounts of radioiodine as a warm nodule, while the remainder of the gland showed decreased uptake. Thyroid hormone levels remained within normal ranges. Cytological findings obtained by fine-needle aspiration biopsy showed papillary carcinoma. Right lobectomy was performed. The histological examinations revealed papillary carcinoma embedded within adenomatous thyroid tissue. It is probable that the surrounding adenomatous tissue accumulated radioiodine, since the warm nodule on 123I scan was larger than the size of the carcinoma. Examinations of the gastrointestinal tract revealed the presence of poorly differentiated adenocarcinoma in the stomach and well differentiated adenocarcinoma (carcinoma in adenoma) in the rectum. Expressions of ras p21 and p53 were examined immunohistochemically in these carcinoma tissues. The ras p21 product was clearly detected in not only the thyroid carcinoma but in a part of the surrounding adenomatous regions as well. Both ras p21 and p53 proteins were observed in the rectal cancer tissue. In contrast, these oncoproteins were not found in the gastric cancer tissue. In this case ras oncogene activation may be an early event in the tumorigenic process of the thyroid and rectum. However, different genetic alterations seem to occur during the development of these three carcinomas. PMID- 8001693 TI - [The prevalence of antithyroid antibodies and long term follow-up in patients with lipiodol iodine-induced goiter]. AB - We have carried out a follow-up study on iodine-induced goiter to clarify whether or not iodine could be a factor in the progression as well as the promotion of thyroid autoimmunity. We selected 143 women of child-bearing age without any previous thyroid disorders who had received hysterosalpingography (H.S.G.). 45 Sex and age-matched healthy subjects were chosen as controls. Serum nonhormonal iodine (S.N.I.) levels, frequency of goiter and antimicrosomal antibody (MCHA) in all the Lipiodol-cases were significantly higher than those in the controls (p < 0.001, < 0.01 and < 0.01), respectively. When the subjects were divided into 9 groups according to the duration of each 5 months after H.S.G., serum TSH and S.N.I. levels, incidence of goiter and MCHA in the initial group were significantly higher than those in the other groups (p < 0.05). The S.N.I. levels became normalized in 30 months after H.S.G. and the goiters disappeared in almost the same duration, while the incidence of higher MCHA titers declined gradually but significantly around 40 months after H.S.G. compared with that in the first 5 months after H.S.G. (p < 0.05). The frequency of goiter and MCHA in 44 cases after a 6-39 month follow-up decreased significantly compared to that in the initial group (p < 0.05). Therefore, we tried an individual longitudinal follow up study on MCHA titer in 12 cases for 35-103 months, resulting in a significant reduction or negativeness of the titer in 6 cases. Likewise, MCHA titers in all cases decreased significantly (p < 0.05) on later evaluation. The present data suggest that iodine in Lipiodol administered via the vagina will act not only as the promoting factor, but as an aggravating agent for thyroid autoimmunity. PMID- 8001694 TI - Homicide mortality in Delaware: variations by age, race and sex. AB - Recently, the subject of violence and its consequences has garnered increasing media attention. Health professionals and policy makers have also expressed concern about violence in our society. There are ample scientific data that illustrate the magnitude of the problem of violent death, especially among young males, in the United States. This article presents available mortality data indicating the magnitude of the problem of violent death among Delaware residents. In specific, the discussion examines variations by age, race, and sex and reveals that Delaware mortality rates for Homicide and Legal Intervention are significantly lower than U.S. rates, especially among black males. PMID- 8001696 TI - Medicare system will be physician's route to information highway. PMID- 8001695 TI - The epidemiology of Lyme disease in Delaware 1989-1992. AB - OBJECTIVES: The study was conducted to describe the temporal, geographic, demographic and treatment characteristics of Lyme disease in Delaware and to assist health planners in developing and implementing control strategies. METHODS: All physician-submitted Centers for Disease Control and Prevention (CDC) follow-up Lyme disease report forms from 1989 through 1992 were reviewed for completeness. Data were gathered from completed forms only. All cases were classified according to the 1990 CDC surveillance case definition. Cases were further subdivided into two groups. Antibiotic usage patterns were then identified for each group. Data on the percentage of infected ticks by county were obtained from a 1988 study conducted by the University of Delaware; Delaware Health and Social Services, Division of Public Health; and the Department of Natural Resources and Environmental Control. RESULTS: Reported cases of Lyme disease increased 246 percent between 1989 and 1992. The 1992 statewide incidence rate was 12.6 cases per 100,000 population. Whites were four times more likely to contract Lyme disease than were blacks. The majority of cases were reported between June and October. The number of patients being treated with oral antibiotics for localized disease for three weeks or longer increased from 52 percent in 1991 to 94 percent in 1992. Ixodid ticks infected with Borrelia burgdorferi were found in all three counties. CONCLUSION: The Delaware State Board of Health made Lyme disease reportable in September 1989. This requirement increased the quality of Lyme disease surveillance; however, the disease is probably under-reported since Delaware does not actively solicit Lyme disease reports. Delaware's case data reflect national data which indicate an increase in reported cases. A trend toward longer duration of treatment for localized Lyme disease is evident. PMID- 8001697 TI - Development of murine pre-T cells into gamma delta T-cell receptor bearing cells. AB - Murine T cells bearing the gamma delta T-cell receptor (gamma delta TCR) are the major lymphocyte subset in the thymus early in fetal development, and postnatally they are the major population of T cells in the epithelia of nonlymphoid tissues including the intestine, skin, tongue, lung, and reproductive organs. The site of origin of gamma delta T-cell precursors (pre-T cells) changes during fetal development, reflecting the sites of active hematopoiesis. In addition, the pattern of expression of specific gamma delta TCR variable (V) region genes changes during fetal and neonatal development, and is unique in different epithelial tissues postnatally. We herein review the literature describing these developmental changes and provide a model for the developmental pathways of murine gamma delta T cells. PMID- 8001698 TI - Mutation "white pupae" in the integument of Ceratitis capitata affects both defense and melanogenesis. AB - Studying defense and melanogenesis processes in the cuticle of the "white pupae" (wp) and "dark pupae" (dp) mutant strains of Ceratitis capitata, we showed that both processes function equally well only in the cuticle of dp mutants, as in the wild-type cuticle. The cuticle of wp mutants lacks the ability to form Escherichia coli aggregates and to melanize in vivo. However, in this mutant, tyrosinase and dopachrome conversion factor activities, as well as melanin content and nonself-recognition proteins are expressed as in the wild strain. The present results indicate that the inability of wp mutant cuticle to immobilize E. coli seems to be due to lack of suitable site(s) on nonself-recognition proteins for adduct formation with tyrosine derivatives by the action of tyrosinase, and the inability to melanize, very probably due to deficiency of tyrosine derivatives (tanning precursors). PMID- 8001699 TI - Immunostimulation of tiger shrimp (Penaeus monodon) hemocytes for generation of microbicidal substances: analysis of reactive oxygen species. AB - NBT staining was used to determine the presence of superoxide anions (O2-) produced by tiger shrimp (Penaeus monodon) hemocytes attached to a coverslip. When cells were treated with beta-glucan, blue granules were observed in 41% of studied hemocyte cytoplasm. For zymosan-treated, PMA-treated, and control cells, the percentages of hemocytes showing similar blue granules were 31, 9, and 5%, respectively. A comparison of stimulative effects on 15 hemocyte suspensions, each collected from a single tiger shrimp, showed that beta-glucan had the strongest effect on intracellular O2- generation, followed by zymosan and PMA (2.5, 2, and 1.3 times greater than the O2- generated by the control group, respectively). After oxidizing phenol red to measure the amounts of hydrogen peroxide (H2O2) produced by the hemocytes, we found that beta-glucan had the strongest stimulative effect (12.2 nmol/mg protein), followed by zymosan and PMA (7.2 and 2.6 nmol/mg, respectively). However, a luminol-enhanced chemiluminescence analysis of hypochlorites (OCl-) produced by the experimental hemocytes showed that neither zymosan nor beta-glucan had a stimulative effect on OCl- production. However, following PMA stimulation, hemocyte chemiluminescence was detected although only at 1.7 mV. Using H2O2 as substrate and guaiacol as an electron acceptor, the enzyme activity of crude enzyme extract derived from broken hemocytes was analyzed; enzyme activity similar to that of human myeloperoxidase (MPO) (0.104 U/mg protein) was observed. The data showed that only PMA had any stimulative effect on MPO-like enzyme activity (2.23 times that of the control group); zymosan and beta-glucan did not have any observable effects on this specific enzyme activity. This is the first documented demonstration of a respiratory burst in shrimp hemocytes. PMID- 8001700 TI - Characterization of immunoreactive TNF alpha molecules in the gastropod Biomphalaria glabrata. AB - In recent years, several studies have demonstrated the existence of cytokine-like molecules in invertebrates, therefore suggesting that cytokines may have been conserved throughout evolution. In this study, we investigated the presence of immunoreactive TNF alpha (ir TNF alpha) in the gastropod mollusc Biomphalaria glabrata, the specific intermediate host for the trematode Schistosoma mansoni. Immunocytochemical study indicated the presence of ir TNF alpha in mollusc hemocytes corresponding to a 53-kDa molecule detected by western blot analysis. Using ELISA tests, we demonstrated the presence of substantial amounts of ir TNF alpha in hemolymph, that were significantly decreased during the S. mansoni infection. The possible role of ir TNF alpha in the regulation of mollusc immune functions and in the host-parasite relationship is discussed. PMID- 8001701 TI - Apoptosis in thymus of adult Xenopus laevis. AB - Thymocyte apoptosis in adult Xenopus laevis is demonstrated on agarose gels and is quantified by propidium iodide incorporation using flow cytometry. Basal apoptotic levels are increased after in vitro exposure to a glucocorticoid, dexamethasone (DEX), and to the lectin, phytohemagglutinin (PHA). To determine the role that newly introduced antigenic determinants may play in this regard, a repertoire of altered-self antigens was created by exposing thymuses in vitro to trinitrobenzene sulfonic acid (TNBS) thereby derivatizing self-cells and proteins via 2,4,6-trinitrophenyl-acetic acid conjugation. An increase in apoptosis in TNBS-treated thymuses is observed. Thus, the thymocytes of adult Xenopus laevis are susceptible to apoptosis when induced by a glucocorticoid, a lectin, and by altered self, antigen activation. PMID- 8001702 TI - Mitogen-activated axolotl (Ambystoma mexicanum) splenocytes produce a cytokine that promotes growth of homologous lymphoblasts. AB - Culture supernatants (PHA-SNs) from axolotl splenocytes cultured with phytohemagglutinin-P (PHA) in medium supplemented with bovine serum albumin (BSA) were collected after 1, 2, and 3 days, pooled, treated to remove residual PHA, precipitated with saturated ammonium sulfate, dialyzed, aliquoted, and stored at 20 degrees C. PHA-SNs stimulated proliferation of homologous lymphoblasts, but not resting splenocytes. SDS-PAGE of metabolically labeled PHA-SNs revealed a band between 14 and 21 kDa. This corresponds to the M(r) of the gel fractions with biological stimulatory activity eluted from PHA-SNs. Blasts absorbed significant bioactivity of PHA-SNs whereas freshly harvested splenocytes did not. Although splenocytes cultured in medium supplemented with 1% fetal bovine serum (FBS) did not proliferate in response to PHA, they did secrete a cytokine with lymphoblast growth-promoting activity. Furthermore, PHA-induced lymphoblasts, initially cultured in medium supplemented with 0.25% BSA, could proliferate in response to PHA-SNs in 1% FBS-supplemented medium. PMID- 8001703 TI - Early thymic regeneration after irradiation. AB - Whole body irradiation produces profound thymic atrophy. After sublethal irradiation, regeneration begins promptly and the earliest regeneration is from radioresistant intrathymic precursors. The progeny of these precursors expand rapidly and restore thymic cellularity to near normal within 2 weeks. We have used monoclonal antibodies specific for a variety of differentiation markers of the T lineage to analyze the early events in thymic regeneration. A three-color flow microfluorometric analysis revealed that the majority of the cells found early in the regenerative process have the phenotype of mature T cells. These include CD4-/CD8-; CD3hi as well as CD4+/CD8-; CD3hi and Cd4-/CD8+; CD3hi. The proportion of cells with mature phenotypes declines rapidly between day 6 and day 12. Not all of the early appearing cells have mature phenotypes. Among the early cells that do not express CD3 are both CD4 and CD8 single positive cells that express HSA and resemble the intrathymic precursors found in other systems. In these mice CD4 single positive predominate. There are other cells that are HSA positive but express low levels of CD4 and very low levels of Thy-1. These appear to include the earliest members of the T-lineage. In addition to relatively mature conventional T cells and early progenitors, the early developing population includes cells that express markers of the T-cell lineage including the T-cell receptor but do not express Thy-1. These Thy-1 negative T cells comprise a significant number of the earliest cells found after regeneration. PMID- 8001704 TI - [Islets of langerhans and pancreas transplantation tomorrow]. AB - Pancreatic tissue grafting as a substitution for insulin deficiency of diabetes is by far the most physiological therapeutic approach of the disease. Both islets and pancreatic gland have been successfully implanted in experimental animal diabetes and in patients, resulting in full normalisation of glucose homeostasis and, in animals, prevention of chronic complications. The need for heavy immunosuppressive drugs is a major drawback not yet overcome and auto and cotransplantation have limited indications. The future lies in intensive research aiming at the discovery of alternative strategies to avoid immunosuppression. Immunoprotection and immunoalteration are attempts to hide or delete harmful pancreatic antigens. Perfusion of MHC soluble donor antigens, anticytokine treatment, xenogenic bone marrow chimerism, use of genetically modified islets, intrathymic islet graft to induce donor specific unresponsiveness are among the numerous trials in progress. Parallely islet banking by cryopreservation and development of a physiological beta cell line are also needed and improving but the absence of a biological marker of pancreatic tissue rejection is a cruel lack. Even only one achievement among these trials could be enough to see the explosion of the development of pancreatic tissue graft. While waiting for that success, it could be wise to accept that such a graft can already bring an amelioration with partial insulin restoration before being able to give a complete cure. We have also to keep in mind that animal models are far away from diabetic patients and much more easy to treat. It is not an unrealistic dream to claim that a xenogenic pancreatic tissue graft without any immunosuppression will be available very soon for every diabetic patient. PMID- 8001705 TI - [Artificial and bioartificial pancreas for the treatment of diabetes mellitus]. AB - The development of an artificial pancreas, a system in which insulin delivery would be regulated continuously by concomitant glucose levels, has been for a long time considered as a dream by diabetologists and diabetic patients. Two approaches are possible. The first one, electromechanical, consists of a glucose sensor, a computer and an insulin pump. Its development may be hindered by the inadequate biocompatibility of the glucose sensor. This led to consider at first the use of a disposable glucose sensor as part of a continuous glucose monitoring system. The second approach aims at developing a bioartificial pancreas, in which isolated islets of Langerhans would be protected against immune rejection by an artificial membrane permeable to glucose and insulin but not so to factors responsible for immune rejection. Thus, it may become possible to transplant a large number of patients before the onset of diabetic complications with xenogeneic islets, without need for any immunosuppression. Promises and obstacles of these two approaches are described herein. PMID- 8001706 TI - [Insulin analogs]. AB - The replacement of some amino-acids in the insulin molecule results in analogues with improved therapeutic properties. Insulin analogues in a monomeric form are absorbed more quickly than hexameric insulin after subcutaneous administration. Bioactivity must be similar to that of insulin without any enhancement of mitogenic properties due to an increase of the affinity for IGF1 receptor. Lys B28-Pro B29 analogue is under clinical investigation to answer the following questions: does this analogue administered immediately before meal al decrease glycaemic excursions and the number of hypoglycemic episodes after meals compared to regular insulin administered 30 minutes before meal? PMID- 8001707 TI - [Alternative routes for insulin administration]. AB - Ideally, insulin administration should be done through portal route, with a precise kinetic. It should also lead to a reproducible biologic effect, with minimal side-effects and be acceptable for the majority of diabetic patients. Many alternative routes of insulin administration try to fulfill one or more of these criteria. Intraperitoneal route is already used with implantable pumps. It has proven safety and metabolic efficacy, particularly upon the reduction of severe hypoglycaemia. Nasal route could provide a rapid kinetic, but its long term utilisation depends on improvement of bioavailability and studies of local toxicity. Results concerning intrabronchic insulin seem promising, but are still preliminary. In the future, the choice among these alternative routes of insulin administration will be guided by the development of a closed-loop system. PMID- 8001709 TI - [Preventive treatment of diabetic microangiopathy: blocking the pathogenic mechanisms]. AB - The development of drugs in order to block metabolic pathway of glucose responsible for diabetic vascular dysfunction is in progress. Aldose reductase inhibitors prevent or reduce the different components of vascular dysfunction, cataract, neuropathy and nephropathy in animal models of diabetes. Promising results have been observed in diabetic patients concerning the prevention of neuropathy and of retinopathy. Larger scale studies with the second generation compounds are in progress. Glycation inhibitors, mainly aminoguanidine, have been shown to prevent or reduce vascular dysfunction and microvascular complications in animal models. Trials in diabetic patients with aminoguanidine are just beginning. Anti-oxidant therapy is also at its early stage of development (vitamin E, vitamin C, alpha lipoic acid). Antiplatelet agents (aspirin, ticlopidine) have been demonstrated to reduce the progression of non proliferative diabetic retinopathy. Angiotensin converting enzyme inhibitors are of particular interest in preventing diabetic glomerulopathy. PMID- 8001708 TI - [Perspectives in the treatment of type 2 diabetes. Role of insulin therapy?]. AB - Independently of its initial mechanism, Type 2 diabetes associates in various degrees disorders in insulin sensibility and secretion. The dissociated insulin resistance among tissues explains the predictable imperfection of insulin therapy in this disease due to frequent weight increase and the potential risks of insulin on atherogenesis raised on the basis of experimental studies. All diabetic subjects are not equally insulin resistant and do not have the same insulin secretory capacity evaluated in practice by means of the response of insulin or C peptide plasma levels to various secreting agents. Intensity and duration of hyperglycaemia, muscular mass, physical activity and way of life, age, weight and fat patterning, the presence of complications, acceptance, education feasibility and compliance are essential in selecting towards insulin therapy. Meanwhile, as the results of the prospective studies in progress become available, it seems that insulin should be restricted to the smallest useful dosage possible and that weight change should be carefully checked within the weeks following initiation of insulin. The future of insulin therapy in Type 2 diabetes requires (1) better selection of patients showing a demonstrated beneficial effect of insulin, (2) the association of insulin with new molecules capable of reducing its dosage and preventing its deleterious effects, (3) a change in the mode of insulin administration, with an appropriate balance between comfort and efficacy, (4) change in the insulin structure towards analogues or compounds related to insulin but with less perverted effects. PMID- 8001710 TI - [Is prevention of type I diabetes mellitus feasible?]. AB - Since the clinical onset of Type 1 diabetes is preceded by an asymptomatic period or prediabetes identified by specific immunogenetic markers, it is possible to imagine specific ways to prevent the onset of the disease in high risk individuals. Such trials will concern mainly first-degree relatives of diabetic patients enrolled into screening programs. The number of individuals necessary to be included in these trials will be function of the therapeutic goals and on the efficacy of the drug in pilot studies in high risk individuals, namely ICA positive subjects with low first phase insulin release during IVGTT. The predominant role of cellular immunity is illustrated in the NOD mouse by the preventive effects of treatments directed toward molecules involved in antigen recognition by autoreactive T cells. Identification of the target autoantigens may lead to specific antigen tolerance. Primary prevention is more speculative and depends on the identification of environmental factors which may initiate beta cell autoimmunity in genetically susceptible individuals. The role of cow's milk proteins has been evocated during retrospective studies. Early interventions in high risk individuals is the only possibility to prevent insulin deficiency. PMID- 8001711 TI - [Is a gene therapy for diabetic syndromes foreseeable?]. AB - The concepts and methods of gene therapy are summarized in order to assess a possible implication in the treatment of diabetes mellitus. Gene therapy requires identification of the critical genetic defect and then the preparation and introduction of the therapeutic transgene, with an appropriate targeting and a strong regulated expression. The bases of the different human diabetic syndromes are reviewed in their present state of knowledge: they are mostly clarified in the case of MODY, extreme insulin resistance syndromes, and some mitochondrial diabetic syndromes; but still obscure in the case of Type 2 and Type 1 diabetic syndromes. Substantial contributions to the understanding of the pathophysiology of diabetes have been brought by transgenic animal models. Gene therapy of human diabetic syndromes may become available, in an undetermined future, particularly under the forms of insulin secreting transgenic "organoids". Such treatments should be proportionate to the intrinsic severity of the candidate diseases and carefully screened for safety. PMID- 8001712 TI - Non-genetic risk determinants of type 1 diabetes. AB - A low concordance rate of Type 1 diabetes among monozygotic twins clearly indicate that genetic risk factors may be necessary but are not sufficient for the disease to occur. Descriptive epidemiological studies from all over the world have disclosed clear age, sex seasonal and geographical variability of the disease occurrence and also increasing incidence rates by time within countries and among migrant groups indicating that several different non-genetic risk factors are of importance for the etiology of Type 1 diabetes. Analytical epidemiological studies have further indicated exposures that are associated with an increased risk for the disease. Thus, early fetal events such as exposure to viruses and maternal blood-group incompatibility may be non-genetic risk factors associated with the initiation of auto-immunity in the genetically susceptible child. Further, early exposure to cow's milk protein and a high frequency of intake of nitrosamine-rich food may act as initiating events. Other risk determinants such as a high growth rate, exposure to many infectious diseases, a cold environment and stressful life events may promote an already ongoing autoimmune destructive process causing and increased work load on the beta-cell or through induction of lymphokine release. The diversity of risk determinants that are associated with Type 1 diabetes risk points at a complex interaction between the genome and environment and multivariate analyses have disclosed different risk profiles in different age groups. Further epidemiological and experimental studies are necessary to disclose the causal relationship and the mechanism of action of the non-genetic risk determinants to provide a basis for primary prevention in the general population. PMID- 8001713 TI - Increase in thiobarbituric acid-reactive substances and vascular complications in type 2 diabetes mellitus. AB - Lipid peroxidation was assessed by measuring the concentrations of thiobarbituric acid-reactive substances in plasma from 204 Type 2 diabetic patients, relative to 107 controls. The concentrations obtained in diabetic patients (3.08 +/- 0.37 mumol/l) were significantly higher than in controls (2.80 +/- 0.34 mumol/l) (p < 0.0001). Values were also significantly increased in patients with macroangiopathy and/or microangiopathy (3.17 +/- 0.41 mumol/l), relative to patients void of vascular complications (2.92 +/- 0.34 mumol/l) (p < 0.001). Elevated concentrations were independent of the type of vascular complication and their possible associations. In patients without vascular affection, thiobarbituric acid-reactive substances were in significantly higher concentrations in hypertensive (3.07 +/- 0.36 mumol/l) than in normotensive (2.87 +/- 0.29 mumol/l) (p < 0.01) patients. There was a correlation between these values and those of total cholesterol (r = 0.46, p < 0.0001) and triglyceride (r = 0.45, p < 0.0001). Statistical analysis by multivariate logistical regression revealed that among the independent factors (TBARS, APO A1, hypertension, age), thiobarbituric acid-reactive substances constituted the parameter most strongly linked to the existence of vascular complications. This study has evidenced a lipid peroxidation disorder in non insulin- dependent diabetes mellitus, more marked in patients with vascular affection. Thiobarbituric acid-reactive substances appear to be an independent marker of vascular complications in Type 2 diabetes. PMID- 8001714 TI - Combining three different sources as a valid tool to identify known diabetic patients: use in a prevalence study in an Italian local health unit. AB - This study was carried out to validate the prevalence of known diabetes estimated from three different simultaneous sources (medical records from out-patient departments, registers and pharmaceutical prescriptions) as against the diagnosis of family doctors who had received ad hoc training before the study. To this effect, a selected Local Health Unit (Unita Sanitaria Locale or USL) in Bari, southern Italy, was examined. 2917 diabetic patients were found, with a 2.82% prevalence. The prevalence of known diabetes estimated from separate sources was 1.41% from medical records, 1.52% from the registers and 1.59% from prescriptions. With reference to the family doctor's conclusions, sensitivity, positive predictive value and efficiency of medical records were 49.8%, 92.5% and 57.4% of USL registers 53.8%, 95.6% and 61.8% of prescriptions 56.3%, 71.2% and 47.9%. 46% of the diabetic subjects were only identified from one source. In conclusion, by combining several sources of information together, a higher number of diabetic patients are identified than would be done by using separate sources; also, active cooperation from the family practitioners seems to be needed to correct the large number of false positive patients (n = 798) mostly identified from prescriptions. PMID- 8001716 TI - [The diabetic foot: various interpretations by patients of some terms used by physicians in podiatric consultation]. AB - Sixty diabetic patients gave their definitions of 12 terms concerning the diabetic foot. On average, only half of these terms were understood by these patients. The level of correct replies is associated neither with the patient's socio-cultural level nor with other variables such as the socio-demographic determinants (sex, age, life-style). The patient's diabetic history (duration of diabetes, treatment, education relating to complications with lower limbs), and the presence or absence of complications did no affect knowledge. On analyzing the contents of these patient's definitions, we discovered a whole range of different conceptions of this disease. By not verifying the patient's understanding of the words, both doctor and patient alike have no doubts as to their competence to understand them. These divergences could have certain consequences not only at the level of treatment, but also concerning prevention of lower limb's complications. PMID- 8001715 TI - Effect of experimental diabetes on Na/K-ATPase activity in red blood cells, peripheral nerve and kidney. AB - A decrease in Na/K-ATPase activity is probably involved in the pathogenesis of diabetic neuropathy. In human diabetes, Na/K-ATPase activity is almost always studied in red blood cells, readily accessible, and it could represent a marker of predisposition to diabetic neuropathy. But, we wanted to establish whether diabetes induced similar changes of Na/K-ATPase activity in erythrocytes, and in other tissues, especially the peripheral nerve and the kidney. So, we compared Na/K-ATPase activity measured in the erythrocyte, sciatic nerve and kidney of rats with streptozotocin-induced diabetes after 8 weeks (n = 9) and normal rats (n = 9). Na/K-ATPase activity was 39-44% lower in the RBC, sciatic nerve and kidney of diabetic rats compared to controls (RBC: 229 +/- 79 vs. 413 +/- 102 p < 0.05; sciatic nerve: 3250 +/- 692 vs. 5532 +/- 1260 p 0.05; kidney: 12920 +/- 4010 vs. 22410 +/- 5310 p < 0.05; results in nmol Pi.mg protein-1.h-1; mean +/- SD). A significant positive correlation was observed between Na/K-ATPase activities in the red blood cells and sciatic nerve (r = 0.81, p < 0.05) in the whole population of rats. This study shows that diabetes induces a parallel decrease in Na/K-ATPase activity in the red cell, sciatic nerve and kidney. The levels of this enzyme activity are significantly correlated in the red cell and sciatic nerve so that diabetes-induced changes of Na/K-ATPase activity in the erythrocyte seem to reflect those in the peripheral nerve. PMID- 8001717 TI - Course of pancreatic beta cell destruction in prediabetic NOD mice: a histomorphometric evaluation. AB - The course of pancreatic beta cell destruction during the prediabetic period of autoimmune diabetic syndromes is not precisely known. We have analyzed the course of insulitis (n = 140) and the beta cell and lymphocytic volume densities by morphometric methods (n = 80) in NOD mice aged 6 to 45 weeks. In the absence of diabetes the mean beta cell density was only slightly reduced with age: 0.64 +/- 0.04% glandular tissue (mean SEM; n = 12) in 6 wk-old mice, 0.52 +/- 0.06% in 45 wk-old mice (n = 12; ns). However, a minority of pancreases were free of insulitis or showed isolated periinsulitis at the end of the 45-wk follow-up period. Invasive insulitis (i.e. mononuclear cells invading the islet area) was detected in 60-85% of mice from the 12th week on. In non overtly diabetic mice, beta cell density was reduced only when insulitis was invasive in more than 40% of islets: 0.30 +/- 0.03%, (n = 11) vs 0.59 +/- 0.04% (n = 34) in moderately invasive insulitis (p < 0.05). These mice had significant metabolic abnormalities. In diabetic mice, the beta cell density was markedly decreased: 0.02 +/- 0.01% (n = 7; p < 0.001). On the whole, a lymphocytic infiltrate affecting less than 50% of the islet volume was compatible with a normal beta cell density. Beyond this 50% lymphocytic infiltration threshold, beta cell density was tightly and negatively related to the lymphocytic volume density.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8001718 TI - Glycaemic and insulinaemic responses in healthy volunteers upon ingestion of maltitol and hydrogenated glucose syrups. AB - Glycaemic and insulinaemic index of maltitol and maltitol-containing chocolate have been determined in healthy subjects with reference to glucose and compared with those of sucrose solution and sucrose containing chocolate. All maltitol containing products (solutions and chocolate) show a reduced glycaemic index. Insulinaemic index of maltitol solutions is also low, while that of maltitol chocolate remains high. PMID- 8001719 TI - The young diabetic subjects in the Israel Army. AB - Between 1978 to 1986, 145 of the Type 1 diabetic patients under our care reached the age of 18 (military service recruitment age). Of the 77 (45 men, 32 women) who decided to volunteer for service, 60 (35 men, 25 women) responded to a questionnaire relating to the conditions of their military service following its completion-these comprised Group A. Of the 68 patients who did not volunteer for service (20 men, 48 women), 44 patients comprised Group B (10 men, 34 women). Group A and Group B were compared in regard to their diabetes history and diabetes management and control during two periods, 17-18 years and 18-20 years. Group A was also evaluated regarding military employment, working and accommodation conditions and diabetes management during army service. The patients in Group A came from a higher socioeconomic level (p < 0.009) and had a significantly higher educational level (p < 0.008). The men in Group A achieved significantly better diabetes control, as evaluated by HbA1, in both periods compared to all the others in both groups. During army service the patients in Group A underwent fewer hospitalizations than the others and only two of them developed complications, whereas among those in Group B 5 patients developed complications. Our data demonstrate that youngsters with Type 1 diabetes can maintain satisfactory diabetes management and control and can function not only adequately, but often far beyond, in the stressful situations with which they are confronted within the rigid authoritative system of military service. Our data also indicated that diabetic patients wishing to volunteer for such service constitute a selected group with a higher socioeconomic background and a higher motivation to prove themselves. PMID- 8001720 TI - [Papilledema and classification of diabetic retinopathy]. PMID- 8001721 TI - [Diagnosis of coronary insufficiency in diabetics. When, how, why?]. PMID- 8001722 TI - Family planning lessons and challenges. Making programs work. AB - Over the past 30 years, family planning programs have helped millions of people to have the smaller families that they want. As programs have learned how to meet people's needs, contraceptive use has spread rapidly. PMID- 8001723 TI - Tonic immobility and high-intensity calls in a precocial chick as a function of age, diet, and time of day. AB - Tonic immobility (TI) and high-intensity vocalizations are two antipredator behaviors employed by domestic chicks (Gallus gallus) which vary in their function and the proximate mechanisms that govern them. In the present study, we sought to determine the influence of age (3 or 10 days old), diet (control or tryptophan-free), and time of testing (A.M. or P.M.) on the duration of TI and the number of calls produced in domestic chicks. Older chicks remained immobile significantly longer than younger chicks as did subjects on the control diet or those tested at night. However, 3-day-old chicks had significantly shorter TI durations only when tested in the A.M.: TI did not differ between age groups when subjects were tested in the P.M. Three-day-olds called significantly more than 10 day-olds when given the control diet and when tested in the P.M. but vocalization frequencies did not differ between age groups during the A.M. testing or when given the tryptophan-free diet (T-). Vocalization rate (calls/TI duration), however, was significantly greater during the A.M. testing. These results emphasize the importance of considering circadian rhythms and behavioral development. Furthermore, an integrative view of the proximate mechanisms and adaptive functions of TI and high-intensity vocalizations is presented. PMID- 8001724 TI - Metabolic activation of the brain of young rats after exposure to environmental complexity. AB - Autoradiography with 14C-2-deoxyglucose was used to determine brain metabolic activity during the quiet period that follows after daily exploratory experiences in new complex environments. Eight 1-month-old, male Tryon rats were selected from two litters. Pairs of littermates matched by body weight were assigned to one of two conditions: rats housed individually in small home cages as the "impoverished condition," or rats exposed twice daily to changing and complex environments of two large cages with inanimate objects and conspecifics as the "enriched condition." After 4 days, rats were injected with 2-deoxyglucose, placed individually in a home cage and left undisturbed for 90 min until sacrificed. The brains of "enriched" rats were heavier than their "impoverished" littermates, and showed a global trend for metabolic enhancement. They also showed significantly greater amounts of 2-deoxyglucose in occipital cortex (27%), hippocampal subiculum (36%), and nucleus accumbens (40%). PMID- 8001725 TI - Infant salt taste: developmental, methodological, and contextual factors. AB - Two studies investigated the human infant's response to salt during development. In the first study, measures of intake and sucking were obtained from two groups of infants, newborns and 4- to 8-month-olds, in response to brief presentations of two concentrations of salt (0.2 or 0.4 M) and water. For several measures of sucking and for intake, there were significant age and concentration effects. Generally, newborn infants tended to reject saline relative to water more than did 4- to 8-month-old infants. This result, consistent with previously published research, suggests a developmental change in salt acceptability and, probably, sensitivity in the human infant. In the second longitudinal study, the response to salted (0.15 M) versus unsalted formulas was evaluated monthly in infants 2 to 7 months of age. Again, a developmental change was observed: Based on some sucking measures, younger infants appeared to be indifferent to the salted formula relative to the unsalted formula whereas older infants tended to reject the salted formula, presumably because either it was less sweet than the unsalted formulas or because it was novel. These data are consistent with the hypothesis developed from animal model studies that during early human postnatal development, transductive elements sensitive to saltiness mature. PMID- 8001726 TI - Ontogeny of context-specific latent inhibition of conditioned fear: implications for configural associations theory and hippocampal formation development. AB - Latent inhibition of fear conditioning to an auditory cue, is measured by behavioral freezing, was examined in 18- and 23-day-old rats. In Experiment 1, CS preexposure and conditioning occurred in the same context for some rats but in a different context for other rats, and 24 hr separated CS preexposure and conditioning. The 23-day-old rats showed a context-specific latent inhibition effect, but the 18-day-old rats showed no latent inhibition. In Experiment 2, CS preexposure and conditioning occurred in the same training session and both 18- and 23-day-old rats showed latent inhibition. These results were discussed in relation to Wagner's (1976) theory of information processing, hippocampal formation maturation, and function, and Sutherland and Rudy's (1989) configural association theory. PMID- 8001727 TI - Ontogeny of the ionic specificity of sodium appetite in the rat pup. AB - Sodium-deficient adult rats prefer NaCl to other monochloride salts (e.g., Denton, 1991; Schulkin, 1991). However, it is not known when or how this specificity develops. Our experiments charted the development of the ionic specificity of sodium appetite aroused by sodium depletion or intracerebroventricular injection of renin. We compared intake of 3% NaCl to three other monochlorides, potassium (K), ammonium (NH4), and lithium (Li), and calcium chloride (CaCl2) at various ages between 72 hr postnatal and weaning. This revealed a biphasic developmental scheme: The adult pattern of discrimination between the salts emerges between 3 and 18 days of age. Subsequently, the preference for Na over the other salts increases into adulthood. PMID- 8001728 TI - Hand preferences for bimanual feeding in 140 captive chimpanzees (Pan troglodytes): rearing and ontogenetic determinants. AB - Hand preference in bimanual feeding was assessed in 140 captive chimpanzees (Pan troglodytes). Bimanual feeding was defined as the active use of one hand for feeding with the opposite hand holding other food items. In terms of strength of hand preference, adults were more lateralized than sub-adults. Additionally, mother-reared chimpanzees were more lateralized than nursery-reared chimpanzees. The number of subjects with no hand preference was more prevalent in sub-adults compared with young and older adults. Of those subjects with a significant hand preference, a larger proportion exhibited a right-hand preference. These results are discussed in relation to previous reports of handedness and bimanual feeding in gorillas and bonobos. PMID- 8001729 TI - Development of uncoupling between D1- and D2-mediated motor behavior in rats depleted of dopamine as neonates. AB - The D1- and D2-mediation of stimulated motor behavior was studied in pups (Days 10-11) and weanlings (Days 20-21) that had been depleted of dopamine (DA) on postnatal Day 3. Administration of the D1-like agonist SKF 38393 (30.0 mg/kg) or the D2-like agonist quinpirole (3.0 mg/kg) increased the incidence of sniffing and locomotion in intact and DA-depleted animals tested at either age. However, the ability of selective DA antagonists to reduce these stimulated responses interacted with both the depletion and the age at the time of testing. When tested as pups, both the D1 antagonist SCH 23390 (0.2 or 0.4 mg/kg) and the D2 antagonist clebopride (10.0 mg/kg) suppressed the behaviors induced by either class of DA agonist. When tested as weanlings, intact animals exhibited the profile of pups (i.e., either antagonist blocked each agonist). In DA-depleted weanlings, however, only the D1 antagonist blocked the D1 agonist-induced responses and only the D2 antagonist blocked the D2 agonist-induced responses. These data demonstrate that the interactions between D1 and D2 receptors in the expression of stimulated motor behaviors are altered following DA depletions in neonates. Moreover, this change in receptor function occurs sometime between 7 and 13 days after the DA depletion. PMID- 8001730 TI - Looking to the future of the life sciences. PMID- 8001731 TI - Biomedical research: the private sector. PMID- 8001732 TI - Medical research and health care reform. PMID- 8001733 TI - DNA: the double helix and the biomedical revolution at 40 years. PMID- 8001734 TI - Multiple pathway signal transduction by the cAMP-dependent protein kinase. AB - Since its discovery a quarter century ago, the cAMP-dependent protein kinase has been a central model for study of the mode of transduction of second messenger signals; more than 300 protein kinases are now known to play keys roles in cellular control. Multiple cellular events are initiated by the activation of the cAMP-dependent protein kinase and correlated with these events has been the identification of a broad spectrum of protein substrates. From model substrates and inhibitors an excellent understanding has been obtained of the "optimum" sequence for protein phosphorylation by the cAMP-dependent protein kinases, and now, from pioneering crystal structure studies, we are beginning to understand exactly how an optimum substrate can interact with and be efficiently phosphorylated by the kinase. The next important step is for us to understand the full sequence of events that occurs within the cell upon activation of the protein kinase, and it is abundantly evident that this is indeed a complex process. It is not sufficient to simply know which proteins are phosphorylated but it is critical that we understand the dynamics of the events surrounding the phosphorylation of multiple proteins, what factors dictate those dynamics, and what might happen when the sequence of events is perturbed. This review focuses on the first simple question that must be addressed, namely, how might proteins vary as substrates for the cAMP-dependent protein kinase and what ramifications might such variations have for the consequential events within the cell? PMID- 8001735 TI - Introduction: protein motifs. PMID- 8001736 TI - The up-and-down beta-barrel proteins. AB - The up-and-down beta-barrel is a common folding motif found frequently in proteins that bind and transport hydrophobic ligands. It is formed by an array of beta-strands arranged in an antiparallel manner with each strand hydrogen-bonded to neighboring strands nearly always adjacent in the amino acid sequence. The arrangement is completed by forming hydrogen bonds between the first and last strands. The barrel motif so formed produces interior and exterior components. Proteins belonging to this class of up-and-down beta-barrels are found typically to be lipid-binding proteins in which the interior surface forms a cavity or pit that serves as the ligand binding region. Two evolutionarily distinct but structurally related families of such carriers have been identified by comparing known crystal structures. One group found intracellularly uses a 10-stranded beta structure and a second family of proteins typically found extracellularly utilizes an 8-stranded motif. The 10-stranded beta-barrels have a large, hydrophilic water-filled interior cavity that serves as the ligand-binding domain. Hydrophobic lipids such as fatty acids and retinoids bind within the cavity, totally sequestered from the external milieu. The 8-stranded beta-barrel proteins have a hydrophobic pit, which serves as the ligand-binding domain for compounds such as bilins and retinoids. The up-and-down beta-barrel motif appears to be one of nature's primary choices for hydrophobic ligand transport proteins. PMID- 8001737 TI - The animal fatty acid synthase: one gene, one polypeptide, seven enzymes. AB - The animal fatty acid synthase comprises two multifunctional polypeptide chains, each containing seven discrete functional domains, juxtaposed head-to-tail such that two separate centers for fatty acid assembly are formed at the subunit interface. The kinetics and specificities of the component enzymes are well adapted to ensure that, at each of the two centers, the iterative condensation of an acetyl moiety with successive malonyl moieties and complete reduction of the beta-keto intermediates normally results in the formation of palmitic acid as the major product. Nevertheless, utilization of alternative substrates and alternative chain-terminating mechanisms can extend the range of products to include branched-chain, odd carbon-numbered, and shorter chain-length fatty acids. The potential of this multifunctional form of molecular architecture for the elaboration of more complex natural products has been further exploited in microorganisms that, by the use of different fatty acid synthase "modules" that perform variable beta-carbon processing at successive elongation steps, generate a structurally diverse family of polyketides retaining keto, hydroxyl, enoyl, or alkyl functions at specific positions in the carbon chain. PMID- 8001738 TI - Histone H1 zero: a major player in cell differentiation? AB - Histone H1 zero was initially described as a member of the lysine-rich histone class, typically present in nondividing mammalian cells. Since then it has been found in almost every animal or plant species studied. The protein accumulates in terminally differentiated cells that have stopped dividing. It has also been implicated in changes in chromatin structure and function accompanying malignant transformation. Despite its involvement in these fundamental cellular processes, its precise role remains elusive, as do the molecular mechanisms via which it acts. This review is an attempt to summarize and critically discuss the huge relevant literature, trying to highlight the problems that still await answers. PMID- 8001739 TI - Proteases and the emerging role of protease inhibitors in prohormone processing. AB - Peptide hormones and neurotransmitters constitute a large class of neurohumoral agents that mediate cell-cell communication in neuroendocrine systems. Their biosynthesis requires proteolytic processing of inactive protein precursors into active neuropeptides. Elucidation of the proteolytic components required for prohormone processing is important for identifying key proteases that may control the production of neuropeptides. This article compares the subtilisin-like PC1/3 and PC2 processing enzymes identified through molecular biological approaches, and several candidate processing enzymes identified biochemically, including the 'proopiomelanocortin converting enzyme' (PCE) and the 'prohormone thiol protease' (PTP), as well as others of different classes (aspartyl, cysteine, metallo, and serine proteases). A role for PTP in cellular proenkephalin processing is suggested by blockade of forskolin-stimulated (Met)enkephalin production by Ep453 that is converted intracellularly to E-64c, a selective cysteine protease inhibitor that potently inhibits PTP. A possible role for endogenous protease inhibitors in prohormone processing represents a new aspect of cellular mechanisms that may regulate neuropeptide biosynthesis. Future studies of the enzymology and molecular biology of processing enzymes and endogenous protease inhibitors will be necessary to elucidate mechanisms of prohormone processing. PMID- 8001740 TI - Oxidized lipoproteins in atherosclerosis and thrombosis. AB - Oxidized low density lipoproteins (LDL) and autoimmune antibodies against oxidized LDL have been demonstrated in human atherosclerotic lesions; they may enhance the progression of these lesions by 1) enhancing monocyte adhesion and macrophage foam cell generation; 2) inducing smooth muscle cell migration, proliferation, and foam cell generation; 3) enhancing platelet adhesion and aggregation, which may stimulate macrophage foam cell generation and smooth muscle cell proliferation; 4) triggering thrombosis; and 5) impairing vasodilation, which results in increased shear stress. The oxidation of LDL probably occurs in the arterial wall, where it is sequestered from circulating antioxidants. Atherosclerotic arterial walls contain increased levels of redox active metal ions, and the LDL of patients with atherosclerotic cardiovascular disease are more susceptible to oxidation, possibly as a result of reduced endogenous antioxidants such as vitamin E. Dietary supplementation with vitamin E (up to 1,000 IU/day) or administration of probucol reduce the oxidation rate of LDL and may significantly decrease the risk of coronary heart disease. PMID- 8001741 TI - Novel mechanisms in chemically induced hepatotoxicity. AB - This review focuses on cellular events that modulate hepatotoxicity subsequent to initial liver insult. Cellular events that determine the nature and extent of hepatotoxic injury and the ultimate outcome of that injury are also discussed. The roles of cell types other than hepatocytes, hepatocyte organelle-specific processes, and regeneration in progression or recovery from liver injury are emphasized. Leukocyte activities are key events in two distinct hepatotoxicities. Neutrophil-mediated, periportal inflammation appears to play a primary role in progression of alpha-naphthylisothiocyanate-induced cholangiolitic hepatitis. However, a humorally mediated autoimmune response to protein adducts that occurs after anesthesia is critical in onset of halothane-induced hepatitis. New insights into specific events at the hepatocyte level are also emerging. Although reducing gap junctional communication between hepatocytes can protect against progression of liver injury, down-regulation of the subunit proteins (connexins) can isolate neoplastic cells from growth regulation. Acidic intracellular pH characteristic of hypoxia is protective against both hypoxic and toxicant-induced cell injury. In oxidative injury, a pH-mediated mitochondrial permeability transition causes mitochondrial uncoupling and ATP loss and leads to cell death. The ultimate outcome of hepatotoxic injury depends on the extent of tissue repair. Stimulation of tissue repair after a sublethal dose of CCl4 appears to be the central mechanism in protection against death from a subsequent large dose. Taken together, these examples illustrate the importance of events subsequent to initial liver injury as determinants of extent of liver damage. PMID- 8001742 TI - Idiotypic induction of autoimmunity: a new aspect of the idiotypic network. AB - Three different experimental models of autoimmune diseases were induced in naive mice after idiotypic immunization. 1) systemic lupus erythematosus (SLE) after injection of anti-DNA antibodies carrying the pathogenic Id-16/6; 2) anti phospholipid syndrome (APLS) after immunization with anti-cardiolipin antibodies (having the pathogenic H-3 and MIV-7 Ids); and 3) Wegener's granulomatosis (WG) induced with anti-neutrophile cytoplasmic antibodies (ANCA). In all three experiments the mice developed the respective anti-Id antibodies (Ab2), and, after a follow-up period of 4-8 months anti-anti-Id (Ab3) were generated by the immunized mice. The latter antibodies (Ab3) had the binding characteristics of the respective autoantibodies (Ab1) used in the first immunization. The appearance of auto-antibodies in the sera of the mice was associated with emergence of all the typical clinical and laboratory findings seen in patients with SLE, APLS, and WG, respectively. We suggest that in some autoimmune diseases, especially in those in which the presumed autoantigen is not immunogenic (e.g., DNA, cardiolipin), the disease may follow a common infection: The antibodies against the infecting agent may carry a pathogenic idiotype of a specific autoantibody. In a subject prone to autoimmunity (genetic, hormonal, immunologic factors), the pathogenic idiotype will progress in dysregulating the immune system to evolve into a clinical overt autoimmune disease. PMID- 8001743 TI - Methionine restriction increases blood glutathione and longevity in F344 rats. AB - Little is known about the biochemical mechanisms responsible for the biological aging process. Our previous results and those of others suggest that one possible mechanism is based on the loss of glutathione (GSH), a multifunctional tripeptide present in high concentrations in nearly all living cells. The recent finding that life-long dietary restriction of the GSH precursor methionine (Met) resulted in increased longevity in rats led us to hypothesize that adaptive changes in Met and GSH metabolism had occurred, leading to enhanced GSH status. To test this, blood and tissue GSH levels were measured at different ages throughout the life span in F344 rats on control or Met-restricted diets. Met restriction resulted in a 42% increase in mean and 44% increase in maximum life span, and in 43% lower body weight compared to controls (P < 0.001). Increases in blood GSH levels of 81% and 164% were observed in mature and old Met-restricted animals, respectively (P < 0.001). Liver was apparently the source for this increase as hepatic GSH levels decreased to 40% of controls. Except for a 25% decrease in kidney, GSH was unchanged in other tissues. All changes in GSH occurred as early as 2 months after the start of the diet. Altogether, these results suggest that dramatic adaptations in sulfur amino acid metabolism occur as a result of chronic Met restriction, leading to increases in blood GSH levels and conservation of tissue GSH during aging. PMID- 8001744 TI - Bile acid synthesis from cholesterol: regulatory and auxiliary pathways. AB - Bile acid synthesis from cholesterol can occur via two pathways, one initiated by sterol 27-hydroxylase activity or one initiated by that of cholesterol 7 alpha hydroxylase. In contrast to cholesterol 7 alpha-hydroxylase, which is found in the liver, sterol 27-hydroxylase is a widely distributed mitochondrial enzyme with high activity in vascular endothelial cells. Although both pathways lead to the production of chenodeoxycholic and cholic acids, the key step, 7 alpha hydroxylation, is governed by two different enzymes. Both 27-hydroxycholesterol and 3 beta-hydroxy-5-cholestenoic acid, the metabolites of cholesterol occurring via sterol 27-hydroxylase activity, normally circulate in plasma. After their uptake by the liver they are metabolized mostly to chenodeoxycholic acid, which down-regulates the activity of cholesterol 7 alpha-hydroxylase, the rate-limiting step for the production of bile acids in the liver. Because of this relationship and also in view of the accelerated atherosclerosis and cholesterol deposition in tissues that occur as a consequence of genetically determined sterol 27 hydroxylase deficiency and of the potent biologic effect of 27-hydroxycholesterol in cell culture, it is proposed that this metabolic pathway serves a regulatory function. The pathway beginning with cholesterol 7 alpha-hydroxylation is modulated by genetic, hormonal, and probably dietary factors, and becomes most prominent with the interruption of the enterohepatic circulation of bile acids. PMID- 8001745 TI - The interleukin-1 family: 10 years of discovery. AB - Ten years ago the cloning of two interleukin-1 molecules (IL-1 alpha and IL-1 beta) resolved the question of whether a single polypeptide could evoke a wide variety of biological effects. During the past decade, the biology of IL-1 has greatly expanded our understanding of how the host responds to external challenges, such as injury and infection, as well as its role in several diseases. We learned of the remarkable potency of IL-1 in the femtomolar range and of its ability to induce a response by triggering only one or two receptors per cell. Unexpectedly, the IL-1 family of genes, receptors and associated molecules have been linked to those of Drosophila, nematodes, and microorganisms and IL-1 signal transduction is similar to that observed after cellular stress. The cloning of IL-1 opened other avenues of fundamental biological interest. For example, in addition to the two agonist molecules IL-1 alpha and IL-1 beta, a third member of the IL-1 gene family is a specific, high affinity receptor antagonist (IL-1 receptor antagonist). That this third member of the IL-1 family inhibits the other two is characteristic of the tight control over production and activity exerted on IL-1. Although IL-1 contributes to the pathogenesis of many diseases, a small amount appears to be needed to combat infection and initiate healing processes. This article highlights 10 years of discoveries on IL-1. PMID- 8001746 TI - [Breast diagnosis: is there a clinical preference among the methods?]. PMID- 8001747 TI - [Blood transfusion and blood product risks and alternatives (from the civil law viewpoint of the judge)]. PMID- 8001748 TI - [Increased mortality in home delivery]. PMID- 8001749 TI - [Indications, technique and results of ultrasound guided punch biopsy in breast diagnosis (n=307)]. AB - From May 1, 1992, to April 30, 1993, we performed 307 ultrasonic guided high speed punch biopsies. In 119 of the 307 women, we dispensed with further surgical and histological procedures when the tentative diagnosis from complementary mammary diagnostic procedures revealed no pathological findings and concurred with the histological results of the punch biopsy. In 188 women, the biopsy was followed by surgical intervention and correlation of the histological findings. This group of patients showed a sensitivity of 98%, a specificity and positive prognostic value of 100%, and a negative prognostic value of 91%. If we combine the results of the complementary mammary diagnostic (including the punch biopsy), then the sensitivity, specificity, and positive and negative prognostic values for this surgically and histologically confirmed group of patients all reach 100%. In trained hands, the ultrasonic guided high-speed punch is a reliable means of determining the histological nature of lesions detected in ultrasonic scans. This technique has been perfected in our facility. Along with preoperative carcinoma detection, it permits us to avoid unnecessary operations when under defined conditions there are no pathological findings. PMID- 8001750 TI - [The prognostic significance of cathepsin D in primary breast cancer]. AB - The prognostic significance of the lysosomal protease cathepsin D in breast cancer was evaluated in a retrospective study. Cathepsin D was measured in 346 deep-frozen (-70 degrees C) cytosol specimens of primary breast carcinomas (1982 1990). Among the established prognostic factors, only axillary lymph node involvement correlated with the expression of cathepsin D (> 40/60 pmol/mg) (p = 0.04-0.05). Univariate analyses of disease-free survival (DFS) and overall survival (OS) showed, that the expression of cathepsin D had no effect on the prognosis either in the whole population of breast cancer patients during long term follow-up (n = 302; median observation time 51 months) or in the group of women with positive lymph nodes (n = 157; 46 months). However, within the group of N0 patients (n = 145; 57 months), high cathepsin D levels were associated with an unfavourable OS, but this relationship was statistically insignificant (p = 0.08-0.13). A similar influence of cathepsin D on DFS could not be demonstrated. Compared to tumour size, grading and receptor status in multivariate analysis, cathepsin D was a more indicative, but finally insignificant prognostic factor for OS. According to these results, cathepsin D may contribute only in combination with other prognostic factors to identify those 20-30% of node negative patients with unfavourable prognosis, who may benefit from adjuvant therapy. PMID- 8001752 TI - [Does previous exposure to oral contraceptives modify survival in breast cancer?]. AB - The influence of a positive history of oral contraceptive (OC) use on survival of breast cancer was studied in 471 patients. 297 (63%) of them were ever users of OCs and 202 (43%) were long-term users (> or = 49 months). The median follow-up amounted to 56 (6-96) months. Except for a significantly higher frequency of poorly differentiated tumours in OC users (p = 0.01) there was no difference in the distribution of histopathological features between OC users and non-users. Nevertheless, compared to non-users OC user showed a significantly increased 5 year-survival (p = 0.017). This effect was strongly correlated with duration of use (p = 0.004) and time since last use (p = 0.02). The influence of OC use achieved significance after a duration of use of four or more years or in case of OC use at the time of diagnosis. The positive effect persisted in multivariate analyses and was mainly attributed to long-term OC users with tumours of a generally expected poor prognosis. PMID- 8001751 TI - [Histologic regression of breast cancer after primary (neoadjuvant) chemotherapy]. AB - Primary (neoadjuvant) chemotherapy of locally advanced breast carcinomas is performed to locally reduce the tumour mass and to improve the operability. Recently, the indication for primary chemotherapy has been extended for preoperative treatment in breast conserving surgery. In an ongoing clinical trial we examined the resection specimens of 51 mammary carcinomas after primary chemotherapy. These patients had received a neoadjuvant therapy with epirubicin/cyclophosphamide for size reduction of large (> 3 cm) but operable tumours (pretreatment median tumour size 4.5 cm by mammography). The tumour response was evaluated pathologically and compared with the clinical tumour regression that was observed in over two-thirds of all cases. We classified the regressive changes using a semiquantitative scoring system from 0 to 4 (0 = no effect, 1 = resorption and tumour sclerosis, 2 = minimal residual invasive tumour [< 0.5 cm], 3 = residual noninvasive tumour only, 4 = no tumour detectable). The aim of this study was to evaluate the improvement of operability objectively and to correlate the histology of the primary tumour with the response to treatment. With invasive lobular carcinomas, the tumour size after therapy was reduced less than average and irrespective of the amount of histological tumour cell reduction, largely due to the stromal content of these neoplasms. Invasive ductal carcinomas with extensive or predominant intraductal component also underwent only a slight decrease in tumour size; this was because of the lack of tumour response with the intraductal component. Well differentiated tubular carcinomas were particularly resistant to primary chemotherapy.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8001753 TI - [Psychological disease adjustment in breast cancer patients]. AB - In a prospective follow-up study, attention was focused on adjustment to disease in breast cancer patients one year after diagnosis. Prebioptic data was collected in the original patient group consisting of 95 women with mammary tissue findings that required clarification. Twenty-nine women with histological confirmation of breast cancer and 37 patients of the control group with benign histological findings were recontacted after an interval of one year. Data was collected by means of psychological test questionnaires (STAI, SVF, FPI, CIP-DS), the patients with breast cancer were given an additional problem-oriented questionnaire about coping with disease, compiled by the author. Most denied having disease-related fears-progression of the disease, premature death; instead, marked sleep disturbances, regularly, recurring nightmares, and depressed states of mind characterized the psychosomatic correlate of the mental burden. The psychological consequences of cancer are related to some extent to the stage of tumour growth at the time of diagnosis; the process of social reintegration appears to be facilitated in women whose biopsy operation did not involve removal of a breast. An clear characterization of breast cancer patients could not be established using psychological testing procedures one year after diagnosis of the disease. PMID- 8001754 TI - [Treatment of endometriosis with the GnRH agonist buserelin (Suprecur): a multicenter study]. AB - A phase III multicentre study was carried out with the GnRH agonist buserelin (Suprecur) at five university institutions (Dept. of Obstetrics and Gynaecology of Essen, Kiel, Tubingen, Munster and Erlangen) to evaluate the effect of Buserelin (3 x 300 micrograms daily intranasal) on endometriosis for a period of 6 months. Endometriosis was verified by light microscopy in all cases. The data of 430 patients could be evaluated. The extent of the endometriotic lesions was studied before the start and at the end of therapy. The mean age of the patients was 30 +/- 5 years. For 300 patients (66.4%) sterility was a main problem. Previous treatment for endometriosis consisted of operation in 20.5%, treatment with danazol in 16.8% and treatment with gestagens in 11.6% of the patients. Under treatment FSH changed from 11.0 +/- 31.4 mIU/ml to 7.0 +/- 5.6 mIU/ml at the end of therapy; LH from 11.1 +/- 12.9 mIU/ml to 7.4 +/- 7.3 mIU/ml; estradiol from 113.9 +/- 89.0 to 35.9 +/- 60.3 pg/ml and progesterone from 7.2 +/- 11.2 ng/ml to 0.8 +/- 1.4 ng/ml. The effect on endometriosis was judged according to the revised American Fertility Society score (rAFS 1985). The changes of the rAFS score stages were as follows (before/after therapy): Stage 0: 0%/42.8%; stage I: 43.5%/38.5%; stage II: 31.1%/11.2%; stage III: 18.1%/2.2%; stage IV: 6.3%/0.2%. The total mean AFS-stage changed from 1.9 to 0.7. The frequency of clinical symptoms improved (before/after therapy): dysmenorrhoea 65.0%/11.2%; pelvic pain 48.2%/14.1%; pain at the time of gynaelogical examination 40.0%/9.7%.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8001755 TI - [In vitro fertilization in male subfertility--micromanipulation and special techniques for semen preparation]. AB - Poor semen quality is increasingly the reason for human infertility. For couples who cannot be helped by conventional in vitro fertilization (IVF) treatment, micromanipulation methods and special sperm preparation techniques in in vitro fertilization hold considerable promise to enhance fertilization of the egg. "Partial zona dissection" (PZD n = 59) or "subzonal insemination" (SUZI n = 36) were performed in 88 IVF cycles obtaining a fertilization rate between 12.2% and 34.8% depending on the micromanipulation technique applied and a pregnancy rate of 19.2% per embryo transfer. So far ten ongoing pregnancies have occurred and five healthy children have been born. In certain cases of male factor infertility micromanipulation and special sperm preparation techniques therefore represent the only possibility of conceiving. PMID- 8001756 TI - [Do preparation techniques induce ultrastructural sperm damage? An electron microscopic study]. AB - We investigated the possibility of ultrastructural damage to human spermatozoa induced by different sperm preparation techniques. Ejaculates from 20 normozoospermic men were divided into equal aliquots and processed by glass wool filtration, Percoll density gradient centrifugation, and a simple two-step centrifugation procedure which served as a control. Ultrastructural damage was assessed by scanning electron microscopy. Compared with Percoll density gradient centrifugation, glass wool filtration yielded a significantly increased proportion of intact acrosomes (p < 0.05). However, both preparations gave significantly better results than control (p < 0.001 and p < 0.01 for glass wool filtration and Percoll centrifugation, respectively). The significance of the conspicuous bending of sperm tails after Percoll centrifugation is not yet known. In conclusion, both glass wool filtration and Percoll centrifugation are efficient techniques for the accumulation of spermatozoa with intact acrosomes. Because of the higher sperm recovery rate, glass wool filtration appears to be the more appropriate method. PMID- 8001757 TI - [Rupture of a splenic artery aneurysm intra partum]. AB - The rupture of a splenic artery aneurysm in pregnancy and during labour is a rare event with a high maternal and fetal mortality rate. This report is, in view of previously reported cases, on the thirteenth case of a ruptured splenic artery aneurysm reporting survival of both mother and fetus. The etiology, clinical signs, diagnosis and therapy are discussed with reference to consideration of the literature. The necessity of an early differential diagnostic consideration of this rare occurrence is discussed, because this is the only way to achieve survival of mother and fetus. PMID- 8001758 TI - [A mature abdominal pregnancy]. PMID- 8001759 TI - [Giant ovarian cystoma in mature pregnancy]. AB - Ovarian tumours occurring during pregnancy pose considerable problems in respect of diagnosis and treatment. Unexpected difficulties arose in the case of patient suffering from a giant ovarian cystoma which ruptured sub partu and was diagnosed only during an emergency Caesarean section. Ileus occurred on the sixth postoperative day. This had been caused by an operation cloth left in the abdomen following the Caesarean section. The patient was awarded damages of DM 5000,-. PMID- 8001760 TI - Plasmid-mediated virulence genes in non-typhoid Salmonella serovars. AB - Specific non-typhoid Salmonella serovars carry large virulence plasmids that promote sustained extra-intestinal infections. These plasmids all share a highly conserved 8-kb region containing the spv operon, consisting of the regulatory spvR locus and the four structural spvABCD genes. The SpvR protein belongs to the LysR/MetR family of transcriptional activators, and induces spvABCD expression in the stationary phase in response to nutrient limitation. spv expression also depends on the chromosomal stationary phase sigma factor RpoS (KatF), and is markedly induced when salmonellae enter eukaryotic cells. Additional plasmid genes encode complement resistance including the rck locus which is homologous to ail from Yersinia. Rck blocks formation of the complement membrane attack complex on the bacterial surface. Several loci involved in plasmid replication and stable maintenance have also been identified. PMID- 8001761 TI - Random mutagenesis of Legionella pneumophila with mini-Tn10. AB - To more effectively study the genetic basis of Legionnaires' disease, we characterized a system for mini-Tn10 mutagenesis in Legionella pneumophila. The mini-transposons were first electroporated into Legionella on counterselectable vectors expressing altered target site transposases. Then, by simultaneously selecting for the kanamycin-resistance gene within the transposon and counterselecting against the maintenance of the plasmid, we directly and readily isolated strains bearing single chromosomal insertions. Southern hybridization analysis further demonstrated that the insertions were randomly distributed throughout the Legionella genome. The mini-Tn10 insertions were stable during extracellular and intracellular growth, and did not alter the infectivity of L. pneumophila. Thus, this mutagenesis system offers an easy, one-step approach toward isolating large populations of random mutants which can be screened for defects in virulence. PMID- 8001763 TI - Heat shock protein 60 (GroEL) from Porphyromonas gingivalis: molecular cloning and sequence analysis of its gene and purification of the recombinant protein. PMID- 8001762 TI - Role of autolysins in the EDTA-induced lysis of Pseudomonas aeruginosa. AB - Treatment of Pseudomonas aeruginosa with metal ion chelators, especially ethylenediaminetetraacetic acid (EDTA), causes both release of protein lipopolysaccharide complexes and cell death. We have examined the effect of EDTA on P. aeruginosa and found that EDTA does not induce the rapid solubilization of the peptidoglycan sacculus and complete lysis as previously thought; the decrease in optical density of cultures incubated with EDTA is primarily due to the loss of the outer membrane. Of the other potential solubilizers examined, only ethylene-bis(oxyethylenenitrilo)tetraacetic acid (EGTA) resulted in some decrease in optical density. The lytic effect of EDTA on 12 strains of P. aeruginosa was examined and was found to vary greatly between strains; the sensitivity to EDTA varies from between 96% and 10% of the decrease in optical density resulting from incubation of cells with both EDTA and lysozyme. Sensitivity to EDTA is not constant during the growth of P. aeruginosa; in the early exponential phase of growth, cells treated with EDTA exhibit a 82% decrease in optical density after 30 min while in the stationary phase the optical density decreases by only 40%. Nucleic acids were observed to leak from cells following treatment with EDTA and this was greatly facilitated by DNase and RNase. The release of genetic material was much reduced when cells were incubated at 4 degrees C, supporting an enzymatic role in cell wall solubilization. We propose that only small areas of the sacculus become hydrolysed via specific peptidoglycan hydrolases, or autolysin(s), which are activated or de-regulated by EDTA. PMID- 8001764 TI - Relationship between ethanol tolerance, lipid composition and plasma membrane fluidity in Saccharomyces cerevisiae and Kloeckera apiculata. AB - The lipid composition of a strain of each of two yeasts, Saccharomyces cerevisiae and Kloeckera apiculata, with different ethanol tolerances, was determined for cells grown with or without added ethanol. An increase in the proportion of ergosterol, unsaturated fatty acid levels and the maintenance of phospholipid biosynthesis seemed to be responsible for ethanol tolerance. The association of ethanol tolerance of yeast cells with plasma membrane fluidity, measured by fluorescence anisotropy, is discussed. We propose that an increase in plasma membrane fluidity may be correlated with a decrease in the sterol:phospholipid and sterol:protein ratios and an increase in unsaturation index. PMID- 8001765 TI - Ethylbenzene degradation by Pseudomonas fluorescens strain CA-4. AB - Pseudomonas fluorescens strain CA-4 is a bioreactor isolate capable of ethylbenzene degradation. Transposon mutagenesis and enzyme assays have been performed which allow us to propose the ethylbenzene degradative pathway in operation in this strain. Ethylbenzene is initially converted to 2-phenylethanol. This is degraded to phenylacetaldehyde and then to phenylacetic acid. The major inducer of the pathway is ethylbenzene itself. The pathway is regulated by the presence of non-aromatic carbon sources. Oxidation of ethylbenzene is repressed by glutamate, but not by citrate or glucose. A clone from a chromosomal library has been found to complement a mutant deficient in the ability to convert ethylbenzene to 2-phenylethanol. PMID- 8001766 TI - Cloning and sequencing of phospholipase B gene from the yeast Torulaspora delbrueckii. AB - The extracellular phospholipase B gene from baker's yeast Torulaspora delbrueckii was cloned and sequenced. Analysis of DNA sequence data revealed an open reading frame (ORF) encoding a 649-amino acid protein, that included amino acid sequences obtained from the purified enzyme. Comparison of these sequence data with the N terminal amino acid sequence of the enzyme indicated that this secreted protein is synthesized as a large precursor with a 21-amino acid N-terminal extension to the mature enzyme of 628 amino acids. A homology search was carried out between phospholipase B from T. delbrueckii and Penicillium notatum. The deduced amino acid sequence of the cloned phospholipase B was homologous (about 50% identity) to phospholipase B from P. notatum, and contained six conserved regions. The transcriptional level of mRNA of the phospholipase B gene was higher in the cells from early exponential and stationary phases. PMID- 8001767 TI - Transformation of Aspergillus parasiticus using autonomously replicating plasmids from Aspergillus nidulans. AB - A genetic transformation system for the aflatoxin-producing fungus Aspergillus parasiticus using two autonomously replicating plasmids from A. nidulans (ARp1 and pDHG25) is reported. Transformation frequencies using the plasmid pDHG25 were from 5 x 10(2) to 2.5 x 10(4) transformants per 10(6) viable protoplasts and microgram DNA. The stability of the plasmids in the transformants was also studied. This transformation system offers a new opportunity to clone genes related to aflatoxin production using appropriate aflatoxin-defective mutants. PMID- 8001769 TI - Characterization of the aac(6')-Ik gene of Acinetobacter sp. 6. AB - The aac(6')-Ik gene which confers resistance to aminoglycosides in Acinetobacter sp. 6 CIP A165 was characterized. The resistance gene was identified as a coding sequence of 438 bases pairs corresponding to a protein with a calculated mass of 16627 Da. Alignment of aac(6')-Ik with aac(6')-Ig from Acinetobacter haemolyticus indicated 83% identity. Like aac(6')-Ig of A. haemolyticus and aac(6')-Ij of Acinetobacter sp. 13, the aac(6')-Ik gene was apparently located in the chromosome and was species specific. The high degree of identity between aac(6') Ig and -Ik, compared with genomic DNA relationships between the host species, indicated that these genes have diverged from a common ancestor in a parental Acinetobacter species. PMID- 8001768 TI - Transposon-induced pigment-deficient mutants of Porphyromonas gingivalis. AB - Trypsin-like protease activity, hemagglutination activity, and accumulation of heme-containing compounds (black pigment) are considered to be virulence factors of Porphyromonas gingivalis. Transposon-mutagenesis was used for the first time to isolate pigment-deficient mutants. These mutants exhibited simultaneous deficiency in trypsin-like protease activity and hemagglutination activity. Two major membrane-associated proteins, observed by SDS-PAGE with the parent strain, were essentially absent from the mutant strains. Immunoblot analysis indicated that these two proteins correspond to putative hemagglutinin and hemagglutinin/protease products of P. gingivalis. Each mutant contained only one transposon insertion, thus the pleiotropic phenotype resulted from single site specific mutations. The results indicate that trypsin-like protease activity is required for accumulation of protoheme from hemoglobin by P. gingivalis and that genetic and/or physiological linkage exists between trypsin-like protease activity and hemagglutination activity. PMID- 8001770 TI - Optimized conditions for the fermentation of Helicobacter pylori and production of vacuolating cytotoxin. AB - We report here improvements to the growth media and fermentation conditions which result in a substantial increase of Helicobacter pylori growth and in the enhanced production of vacuolating cytotoxin. Addition of glucose to the medium resulted in the increase of cell yield, cell viability and a significant improvement in the production of vacuolating cytotoxin. PMID- 8001772 TI - A haemolytic cell-free preparation of Moraxella bovis confers protection against infectious bovine keratoconjunctivitis. AB - Protection conferred by a cell-free preparation from a haemolytic Moraxella bovis isolate, UQV 148NF, was compared to an equivalent fraction from a non-haemolytic M. bovis isolate, Gordon 26L3, and to a recombinant DNA-derived pili vaccine. Three groups of ten calves were vaccinated twice with one of the three preparations and, together with ten non-vaccinated calves, challenged with virulent M. bovis isolate Dal 2d. Compared to the control group, significant protection was observed in the group receiving the pili vaccine and the group receiving the preparation from haemolytic isolate, UQV 148NF. PMID- 8001771 TI - Genes encoding homologues of three consecutive enzymes in the butyrate/butanol producing pathway of Clostridium acetobutylicum are clustered on the Clostridium difficile chromosome. AB - Screening of a Clostridium difficile lambda EMBL3 gene library with antisera raised against C. difficile culture supernatant identified several clones expressing a 31-kDa protein. A 1.8-kb HindIII fragment subcloned from one of the clones was sufficient for expression of the 31-kDa polypeptide. Southern blot analysis showed a region homologous to this fragment to be present in all of 13 different C. difficile strains tested. Sequence analysis of the 1.8-kb fragment revealed three adjacent open reading frames. A database search showed that these three open reading frames appeared to encode homologues of three consecutive enzymes in the butanol/butyrate-producing pathway of Clostridium acetobutylicum (crotonase, beta-hydroxybutyryl coenzyme A dehydrogenase and thiolase). PMID- 8001773 TI - Effects of proteinase inhibitors on the growth and differentiation of Trypanosoma cruzi. AB - Three proteinase inhibitors, one peptidyl acyloxymethyl ketone (AMK), Z-Phe-Lys CH2-OCO-(2,4,6-Me3)Ph.HCl, and two diazomethyl ketones (DMKs), Z-Phe-Phe-DMK and Z-Phe-Ala-DMK, have been studied for their effects in vitro on the four developmental stages of Trypanosoma cruzi. The three inhibitors penetrated living parasites and inhibited the major cysteine proteinase, cruzipain. The AMK was the most potent inhibitor of cruzipain itself and at 20 microM caused lysis of epimastigotes and trypomastigotes. When at lower concentrations, however, it had little effect on epimastigote growth but reduced metacyclogenesis. The DMKs had no effect against epimastigotes but inhibited differentiation to metacyclics. All three inhibitors markedly reduced infection of Vero cells by the parasite and the multiplication of the intracellular amastigotes, whereas release of trypomastigotes was almost entirely prevented. The results confirm the importance of cysteine proteinases in the life cycle of T. cruzi, and suggest that the differentiation steps are the most susceptible to cysteine proteinase inhibitors. PMID- 8001775 TI - Coordination of germ tube formation and surface antigen expression in Candida albicans. AB - If the determinants of shape and cell wall topography are independently regulated and induced in germ tube formation in Candida albicans, these processes may be separable in a non-germ tube forming strain. The expression of several preferentially expressed hyphal surface components in a parental, non-germ tube forming variant, and a germ tube forming revertant strain were examined by indirect immunofluorescence. The proportion of germ tubes expressing the determinants and the morphological localization of expression was similar. Few yeast cells in germ tube cultures bound probes and there was no increase in binding by yeast cells of the variant strain. Extraction with beta mercaptoethanol prior to analysis had little effect on probe binding and the shape of yeast cells were similar. These observations suggest the ability to promote apical expansion in germ tube formation and surface expression of certain markers were coordinately regulated. PMID- 8001774 TI - Regulation of Escherichia coli K5 capsular polysaccharide expression: evidence for involvement of RfaH in the expression of group II capsules. AB - Expression of the Escherichia coli K5 antigen was used as a model system to study the role of known regulators of gene expression on production of group II capsules in E. coli. Only mutations in the rfaH gene had an effect on production of the K5 antigen, abolishing the expression of any detectable capsule at 37 degrees C. None of the mutations studied induced capsule expression at 18 degrees C. A sequence, termed JUMPstart, found in group II capsule gene clusters and upstream of a number of polysaccharide biosynthesis genes in enteric bacteria is homologous to sequences found in RfaH regulated operons. This may indicate a common mode of regulation of these polysaccharide biosynthesis genes by RfaH. PMID- 8001776 TI - A reconsideration of the mechanism of position effect. PMID- 8001777 TI - Genetic variability of the beta-tubulin genes in benzimidazole-susceptible and resistant strains of Haemonchus contortus. AB - Benzimidazole anthelmintics are the most common chemotherapeutic agents used to remove intestinal helminths from farm animals. The development of drug resistance within helminth populations is wide-spread and can render these drugs essentially useless. The mechanism of benzimidazole resistance appears to be common to many species ranging from fungi to nematodes and involves alterations in the genes encoding beta-tubulin. During the selection process resulting in resistance, there must be quantitative changes in the population gene pool. Knowledge of these changes would indicate the mechanisms underlying the spread of resistance in the population, which in turn could be used to design more effective drug administration strategies. To this end we have identified allelic variation at two beta-tubulin genes in Haemonchus contortus using restriction map analysis of individual adults. Extremely high levels of variation were identified at both loci within a susceptible strain. In two independently derived benzimidazole resistant strains, allele frequencies at both loci were significantly different from the susceptible strain but not from each other. The same alleles at both loci, in both resistant strains, were favored by selection with benzimidazoles, suggesting that both loci are involved in determining benzimidazole resistance. These data confirm that changes in allele frequency, rather than novel genetic rearrangements induced by exposure to the drug, explain the changes associated with benzimidazole resistance. These results also show that any DNA based test for the development of benzimidazole resistance must take into account the frequency of alleles present in the population and not simply test for the presence or absence of specific allelic types. PMID- 8001778 TI - Suppressors of recB mutations in Salmonella typhimurium. AB - Using a screen that directly assesses transductional proficiency, we have isolated suppressors of recB mutations in Salmonella typhimurium. The alleles of sbcB reported here are phenotypically distinct from those isolated in Escherichia coli in that they restore recombination proficiency (Rec+), resistance to ultraviolet light (UVR), and mitomycin C resistance (MCR) in the absence of an accompanying sbcCD mutation. In addition the sbcB alleles reported here are co dominant to sbcB+. We have also isolated insertion and deletion mutants of the sbcB locus. These null mutations suppress only the UVS phenotype of recB mutants. We have also isolated sbcCD mutations, which map near proC. These sbcCD mutations increase the viability, recombination proficiency and MCR of both the transductional recombination suppressors (sbcB1 & sbcB6) and the sbcB null mutations. S. typhimurium recB sbcB1 sbcCD8 strains are 15-fold more recombination proficient than wild-type strains. The increase in transductants in these strains is accompanied by a loss of abortive transductants suggesting that these fragments are accessible to the mutant recombination apparatus. Using tandem duplications, we have constructed sbcB merodiploids and found that, in a recB mutant sbcCD+ genetic background, the sbcB+ allele is dominant to sbcB1 for transductional recombination but co-dominant for UVR and MCR. However, in a recB sbcCD8 genetic background, the sbcB1 mutation is co-dominant to sbcB+ for all phenotypes. Our results lead us to suggest that the SbcB and SbcCD proteins have roles in RecBCD-dependent recombination. PMID- 8001779 TI - Genetic and phenotypic analysis of thirteen essential genes in cytological interval 22F1-2; 23B1-2 reveals novel genes required for neural development in Drosophila. AB - In an attempt to identify mutations in the Drosophila synaptotagmin gene we have isolated many new rearrangements, point mutations and P element insertions in the 22F1-2; 23B1-2 cytological interval on chromosome arm 2L. This interval encompasses 13 cytological bands and is shown to contain 13 essential complementation groups, including decapentaplegic, synaptotagmin and Curly. Through chemical and P element mutagenesis we have isolated seven new deletions, which combined with previously isolated rearrangements, have allowed us to order most genes in the interval. A genomic walk covering approximately 100 kb within this interval spans at least five essential genes as identified by chromosomal aberrations. Preliminary phenotypic characterizations of the mutant phenotype and lethal phase is presented for many mutations. Three loci within this interval are shown to be required for proper neural development. Given that the average number of alleles per complementation group is greater than seven, it is very likely that all essential genes within this cytological interval have been identified. PMID- 8001780 TI - Differential regulation of target genes by different alleles of the segmentation gene hunchback in Drosophila. AB - hunchback (hb) is a key regulatory gene in the early segmentation gene hierarchy of Drosophila. It codes for a transcription factor of the Cys2-His2 zinc finger type and shows two separate zinc finger domains in its coding region. hb forms a morphogenetic gradient in the middle of the embryo that is required for setting the spatial boundaries of several target genes. We have analyzed the molecular lesions found in the different hb alleles and have studied the differential effects of these alleles on a number of such target genes. We find that in mutants in which the HB protein lacks a functional second finger domain, the regulation of the target genes Kruppel (Kr) and knirps (kni) is differentially affected. While this domain is required for the correct regulation of Kr, it is not necessary for the repression of kni. Furthermore, mutations affecting this domain lead to a decreased protein stability. The integration of the expression pattern of target genes was found to be distorted in a second class of mutants between the two finger domains which lead to gain of function or neomorphic phenotypes. The effects of these mutations were studied in detail and it was found that they fall into two classes, the first one interfering with the function of the maternal hb product, the second leading to a delayed segmentation. The function of the latter class appears to be linked to the secondary expression of hb in the parasegment 4 (PS4) stripe at blastoderm stage. PMID- 8001782 TI - X-linked elements associated with negative segregation distortion in the SD system of Drosophila melanogaster. AB - Three elements, M1, M2 and M3, found in a special X chromosome, supp-X(SD), modify the degree and direction of segregation distortion in the SD system of Drosophila melanogaster. The first element, M1, is located between the y and the cv loci, probably close to the y locus. The second element, M2, is located near the cv locus and the third element, M3, is located between the y and the car loci. The M1 element appears to cause a relatively small amount of reduction in the rate of recovery of the SD-72, but not the cn bw, chromosome from SD-72/cn bw males, when raised at 27.5 degrees. The M2 and the M3 elements cause considerable decrease in the recovery rate of the SD-72 chromosome, whereas they increase the recovery rate of the cn bw chromosome. The amount of decrease is nearly the same as the amount of increase for each element. Some type of "switch" mechanism in the directions of distortion is suggested for each of these two elements and their effects appear to be approximately additive. PMID- 8001781 TI - Molecular evolution of the metallothionein gene Mtn in the melanogaster species group: results from Drosophila ananassae. AB - Three distinctly different alleles of the metallothionein gene Mtn have been identified in natural Drosophila melanogaster populations: Mtn.3, Mtn1, and Dp(Mtn1), where the latter designates a tandem duplication of Mtn1. In Drosophila simulans, only Mtn.3-type alleles have been found. It has been suggested that Mtn.3 is the ancestral allele and demonstrated that a presumed two-step transition from Mtn.3 to Mtn1 to Dp(Mtn1) is accompanied by an approximate 5-fold increase in RNA levels. We analyzed the evolutionary genetics of the Mtn locus of Drosophila ananassae, a distant relative of D. melanogaster and D. simulans within the melanogaster species group. The Mtn gene of D. ananassae is most similar to Mtn.3: (i) it is identical with Mtn.3 at the amino acid level, but differs from Mtn1 in its terminal codon; (ii) its 3' UTR contains a characteristic extra DNA segment of about 50 bp which is present in Mtn.3, but lacking in Mtn1; (iii) duplications of Mtn were not found in a worldwide sample of 110 wild D. ananassae chromosomes. However, the intron of the Mtn gene in D. ananassae is only 69 bp long, whereas the length of the Mtn.3 and Mtn1 introns is 265 bp; and it lacks a polypyrimidine stretch upstream of the 3' splice site in contrast to the much greater pyrimidine-richness found in the Mtn.3 and Mtn1 introns. A short intron (67 bp) was also identified in a D. pseudoobscura Mtn allele, suggesting that the short intron is the ancestral form and that the transition from the short to the long intron occurred within the melanogaster species group.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8001783 TI - The Lighten up (Lip) gene of Drosophila melanogaster, a modifier of retroelement expression, position effect variegation and white locus insertion alleles. AB - We are interested in identifying single gene mutations that are involved in trans acting dosage regulation in order to understand further the role of such genes in aneuploid syndromes, various types of dosage compensation as well as in regulatory mechanisms. The Lighten up (Lip) gene in Drosophila melanogaster was identified in a mutagenic screen to detect dominant second site modifiers of white-blood (wbl), a retrotransposon induced allele of the white eye color locus. Lip specifically enhances the phenotype of wbl as well as a subset of other retroelement insertion alleles of white, including the copia-induced allele, white-apricot (wa), and six alleles caused by insertion of I elements. We isolated six alleles of Lip which are all recessive lethal, although phenotypically additive heteroallelic escapers were recovered in some combinations. Lip also suppresses position effect variegation, indicating that it may have a role in chromatin configuration. Additionally, Lip modifies the total transcript abundance of both the blood and copia retrotransposons, having an inverse effect on the steady state level of blood transcripts, while showing a non-additive effect on copia RNA. PMID- 8001784 TI - The thick veins gene of Drosophila is required for dorsoventral polarity of the embryo. AB - We have discovered a new member of the class of genes controlling embryonic dorsoventral patterning. Mutants of the thick veins (tkv) gene have been described previously (as slater alleles) as embryonic lethal, lacking dorsal epidermis, but not as showing a recognizable dorsoventral phenotype. We show here that maternal alteration of function coupled with zygotic reduction of function of tkv is strongly ventralizing. In addition, in double heterozygous combinations in the mother, tkv mutations increase the ventralizing effect of dominant, weakly ventralizing alleles of the maternal effect, dorsoventral genes easter and cactus. An interaction is also seen with zygotic dorsoventral genes: tkv interacts maternally and zygotically in double heterozygotes with decapentaplegic and zygotically with screw in double homozygotes. We conclude that both maternally and zygotically supplied wild-type tkv product can play a role in dorsoventral patterning of the early embryo. On the basis of the phenotype of trans-heterozygous adult escapers, we propose that tkv might act by potentiating the activity of the zygotically acting decapentaplegic gene. PMID- 8001785 TI - Length variation in mitochondrial DNA of the minnow Cyprinella spiloptera. AB - Length differences in animal mitochondrial DNA (mtDNA) are common, frequently due to variation in copy number of direct tandem duplications. While such duplications appear to form without great difficulty in some taxonomic groups, they appear to be relatively short-lived, as typical duplication products are geographically restricted within species and infrequently shared among species. To better understand such length variation, we have studied a tandem and direct duplication of approximately 260 bp in the control region of the cyprinid fish, Cyprinella spiloptera. Restriction site analysis of 38 individuals was used to characterize population structure and the distribution of variation in repeat copy number. This revealed two length variants, including individuals with two or three copies of the repeat, and little geographic structure among populations. No standard length (single copy) genomes were found and heteroplasmy, a common feature of length variation in other taxa, was absent. Nucleotide sequence of tandem duplications and flanking regions localized duplication junctions in the phenylalanine tRNA and near the origin of replication. The locations of these junctions and the stability of folded repeat copies support the hypothesized importance of secondary structures in models of duplication formation. PMID- 8001786 TI - Selection on silent sites in the rodent H3 histone gene family. AB - Selection promoting differential use of synonymous codons has been shown for several unicellular organisms and for Drosophila, but not for mammals. Selection coefficients operating on synonymous codons are likely to be extremely small, so that a very large effective population size is required for selection to overcome the effects of drift. In mammals, codon-usage bias is believed to be determined exclusively by mutation pressure, with differences between genes due to large scale variation in base composition around the genome. The replication-dependent histone genes are expressed at extremely high levels during periods of DNA synthesis, and thus are among the most likely mammalian genes to be affected by selection on synonymous codon usage. We suggest that the extremely biased pattern of codon usage in the H3 genes is determined in part by selection. Silent site G + C content is much higher than expected based on flanking sequence G + C content, compared to other rodent genes with similar silent site base composition but lower levels of expression. Dinucleotide-mediated mutation bias does affect codon usage, but the affect is limited to the choice between G and C in some fourfold degenerate codons. Gene conversion between the two clusters of histone genes has not been an important force in the evolution of the H3 genes, but gene conversion appears to have had some effect within the cluster on chromosome 13. PMID- 8001787 TI - The original pink-eyed dilution mutation (p) arose in Asiatic mice: implications for the H4 minor histocompatibility antigen, Myod1 regulation and the origin of inbred strains. AB - Allelic variation of the mouse pink-eyed dilution (p) gene in common laboratory strains and wild mice was examined by Southern blot and by polymerase chain reaction. In these assays the original p mutation allele found in strains SJL/J, 129/J, B10.129(21m), P/J and FS/Ei most closely matches an Asian Mus musculus allele, confirming anecdotal accounts of the Asian origin of this mutation. In contrast, the wild-type allele found in other common laboratory strains was apparently derived from Mus domesticus. Analysis of chromosome 7 loci both proximal and distal to the p locus demonstrates that strains SJL/J, 129/J, B10.129(21M), P/J and FS/Ei contain DNA segments of varying length derived from M. musculus. Strains 129/J and B10.129(21M) contain the largest segment of M. musculus-derived DNA (about 5 cM), including the loci Myod1, p, three clustered GABAA receptor subunit loci (Gabrg3, Gabra5 and Gabrb3), and Snrpn. The difference in the species origin of genes from this region of chromosome 7 may underlie the basis of the antigenicity of the minor histocompatibility antigen H4, defined by the strain B10.129(21M), and may account for the enhanced Myod1 activity observed in SJL/J mice. PMID- 8001789 TI - Selection intensity for codon bias. AB - The patterns of nonrandom usage of synonymous codons (codon bias) in enteric bacteria were analyzed. Poisson random field (PRF) theory was used to derive the expected distribution of frequencies of nucleotides differing from the ancestral state at aligned sites in a set of DNA sequences. This distribution was applied to synonymous nucleotide polymorphisms and amino acid polymorphisms in the gnd and putP genes of Escherichia coli. For the gnd gene, the average intensity of selection against disfavored synonymous codons was estimated as approximately 7.3 x 10(-9); this value is significantly smaller than the estimated selection intensity against selectively disfavored amino acids in observed polymorphisms (2.0 x 10(-8)), but it is approximately of the same order of magnitude. The selection coefficients for optimal synonymous codons estimated from PRF theory were consistent with independent estimates based on codon usage for threonine and glycine. Across 118 genes in E. coli and Salmonella typhimurium, the distribution of estimated selection coefficients, expressed as multiples of the effective population size, has a mean and standard deviation of 0.5 +/- 0.4. No significant differences were found in the degree of codon bias between conserved positions and replacement positions, suggesting that translational misincorporation is not an important selective constraint among synonymous polymorphic codons in enteric bacteria. However, across the first 100 codons of the genes, conserved amino acids with identical codons have significantly greater codon bias than that of either synonymous or nonidentical codons, suggesting that there are unique selective constraints, perhaps including mRNA secondary structures, in this part of the coding region. PMID- 8001788 TI - Somatic inactivation and reactivation of Ac associated with changes in cytosine methylation and transposase expression. AB - Several metastable Ac alleles at the maize p locus were identified that produced novel pericarp variegation patterns. From the transmission analysis of pericarp sectors, we show that Ac inactivation is a somatic process. Ac excision from P and transactivation of an unlinked Ds was delayed or absent in plants with metastable Ac alleles. These decreases in Ac activity were correlated to increases in cytosine methylation at specific sites near the start of Ac transcription (open reading frame a; ORFa) and at sites in some flanking P sequence. Reactivation of inactive alleles was accompanied by decreased methylation of Ac and P sequences. Using a competitive polymerase chain reaction assay, steady state levels of ORFa transcript were quantitatively compared among the various metastable alleles. We propose that changes in the methylation profile of Ac correspond to changes in Ac activity through the differential accumulation of Ac transcript. PMID- 8001790 TI - Approximate thresholds of interval mapping tests for QTL detection. AB - A general method is proposed for calculating approximate thresholds of interval mapping tests for quantitative trait loci (QTL) detection. Simulation results show that this method, when applied to backcross and F2 populations, gives good approximations and is useful for any situation. Programs which calculate these thresholds for backcross, recombinant inbreds and F2 for any given level and any chromosome with any given distribution of codominant markers were written in Fortran 77 and are available under request. The approach presented here could be used to obtain, after suitable calculations, thresholds for most segregating populations used in QTL mapping experiments. PMID- 8001791 TI - Three additional linkage groups that repress transcription and meiotic recombination in the mating-type region of Schizosaccharomyces pombe. AB - The mating-type genes of Schizosaccharomyces pombe are found at three locations in the same chromosomal region. These genes are in an active configuration at the mat1 locus and in an inactive configuration at the mat2 and mat3 loci. The mechanism that represses transcription of mat2 and mat3 also inactivates other promoters introduced nearby and is accompanied by a block to meiotic recombination in the mat2-mat3 interval, suggesting that this mechanism involves a particular chromatin structure. We present evidence that the transcription and recombination blocks require three newly defined trans-acting loci, clr2, clr3 and clr4, in addition to the previously identified clr1, rik1 and swi6 loci. We also investigated the role of mat2 cis-acting sequences in silencing. Four cis acting elements that repress mat2 in a plasmid context were previously identified. Deletion of two of these elements proved to have little effect in a chromosomal context. However, when combined with mutations in trans-acting genes, deletion of the same two elements greatly enhanced mat2 expression. The observed cumulative effects suggest a redundancy in the silencing mechanism. PMID- 8001792 TI - Glucose repression of fbp1 transcription of Schizosaccharomyces pombe is partially regulated by adenylate cyclase activation by a G protein alpha subunit encoded by gpa2 (git8). AB - In the fission yeast Schizosaccharomyces pombe, genetic studies have identified genes that are required for glucose repression of fbp1 transcription. The git2 gene, also known as cyr1, encodes adenylate cyclase. Adenylate cyclase converts ATP into the second messenger cAMP as part of many eukaryotic signal transduction pathways. The git1, git3, git5, git7, git8 and git10 genes act upstream of adenylate cyclase, presumably encoding an adenylate cyclase activation pathway. In mammalian cells, adenylate cyclase enzymatic activity is regulated by heterotrimeric guanine nucleotide-binding proteins (G proteins). In the budding yeast Saccharomyces cerevisiae, adenylate cyclase enzymatic activity is regulated by monomeric, guanine nucleotide-binding Ras proteins. We show here that git8 is identical to the gpa2 gene that encodes a protein homologous to the alpha subunit of a G protein. Mutations in two additional genes, git3 and git5 are suppressed by gpa2+ in high copy number. Furthermore, a mutation in either git3 or git5 has an additive effect in strains deleted for gpa2 (git8), as it significantly increases expression of an fbp1-lacZ reporter gene. Therefore, git3 and git5 appear to act either in concert with or independently from gpa2 (git8) to regulate adenylate cyclase activity. PMID- 8001793 TI - SPO13 negatively regulates the progression of mitotic and meiotic nuclear division in Saccharomyces cerevisiae. AB - The meiosis-specific yeast gene SPO13 has been previously shown to be required to obtain two successive divisions in meiosis. We report here that vegetative expression of this gene causes a CDC28-dependent cell-cycle arrest at mitosis. Overexpression of SPO13 during meiosis causes a transient block to completion of the meiosis I division and suppresses the inability of cdc28ts strains to execute meiosis II. The spo13 defect can be partially suppressed by conditions that slow progression of the first meiotic division. Based on the results presented below, we propose that SPO13 acts as a meiotic timing function by transiently blocking progression through the meiosis I division, thereby allowing (1) coordination of the first division with assembly of the reductional segregation apparatus, and (2) subsequent entry into a second round of segregation to separate replicated sister chromatids without an intervening S-phase. PMID- 8001794 TI - Spontaneous mutation at the mtr locus in neurospora: the molecular spectrum in wild-type and a mutator strain. AB - Sequence analysis of 34 mtr mutations has yielded the first molecular spectrum of spontaneous mutants in Neurospora crassa. The great majority of the mutations are base substitutions (48%) or deletions (35%). In addition, sequence analysis of the entire mtr region, including the 1472-base pair open reading frame and 1205 base pairs of flanking DNA, was performed in both the Oak Ridge and Mauriceville strains of Neurospora, which are known to be divergent at the DNA level. Sixteen sequence differences between these two strains have been found in the mtr region, with 13 of these in DNA flanking the open reading frame. The differences consisted of base substitutions and small frameshifts at monotonic runs. This set of sequence differences has allowed a comparison of mutations in unselected DNA to those mutations that produce a phenotypic signal. We have isolated a mutator strain (mut-1) of Neurospora in which the spontaneous mutation rate at various loci is as much as 80-fold higher than in the non-mutator (wild type). Twenty-one mtr mutations in the mutator background have been sequenced and compared to the non-mutator spectrum, revealing a striking increase in -1 frameshift mutations. These frameshifts occur exclusively within or adjacent to monotonic runs and can be explained by small slippage events during DNA replication. This argues for a role of the mut-1 gene in this process. PMID- 8001795 TI - Directed replacement of mt A by mt a-1 effects a mating type switch in Neurospora crassa. AB - To test the functions of a mating type genes, we developed an efficient strategy to select transformants of Neurospora crassa in which resident A mating type DNA was replaced by cloned DNA from the mt a idiomorph. Cloned a idiomorphic DNA could specify all functions, including fertility, of a mating type, but only when it replaced A DNA at the mating type locus. Only the mt a-1 region of the a idiomorph was necessary in order to specify a mating type. Gene replacement events involved the homologous sequences flanking the unique mating type idiomorphic DNA, resulting in apparently isogenic a and A strains. These isogenic strains were fertile when crossed with one another, indicating that no determinants outside the transforming DNA are necessary for fertility as a and that no host sequences of A strains interfere with fertility as a. One a replacement strain bore a duplication of the transforming mt a-1 and hph DNA. The duplication strain had unexpected properties. Although mating type segregated 1:1 in crosses of this strain to A, the duplicated regions were efficiently altered during the sexual process to generate a single copy in the progeny. No progeny were recovered that had undergone RIP (repeat induced point mutation) sufficient to inactivate the mt a-1 gene. We infer that the mt a-1 gene is necessary and sufficient to specify a mating type identity in all vegetative and sexual activities. Mt a-1 may also play an essential role in ascosporogenesis after fertilization. PMID- 8001797 TI - [Cloning and expression of the B1 hordein gene of barley (Hordeum vulgare L.) in cells of the cyanobacterium Synechocystis sp. PCC6803 and Escherichia coli]. AB - The hordein B1 gene of Hordeum vulgare L. (variety Donetskii 4) was cloned in cells of Escherichia coli and cyanobacterium Synechocystis sp. PCC6803. For cloning in E. coli, a 2.3-kb Hpa I/EcoR I DNA fragment carrying the hordein B1 gene was inserted into plasmid pBSM13(-), controlled by a lac promoter. The constructed recombinant plasmid pBSB1 provides hordein B1 gene expression in transformed E. coli cells. To introduce the hordein B1 gene into the genome of Synechocystis sp. PCC6803, an integrative vector, containing a fragment of cyanobacterium chromosomal DNA with inserted Tn5 antibiotic resistance genes (KmR, BleoR, StpR) was constructed. A Pvu II-fragment of pBSB1, containing hordein B1 gene under control of the lac promoter, was cloned in the Sma I-site of gene BleoR. The resulting recombinant plasmid was used to transform cyanobacterial cells. One KmR transformants contained a DNA fragment yielding a positive signal during Southern blotting with a [32P]-labeled DNA fragment carrying hordein B1 gene. Western blotting with polyclonal antibodies to barley hordein revealed hordein B1 gene expression in Synechocystis sp. PCC6803. PMID- 8001798 TI - [A beta-casein gene fragment is located in region 1p3 of human chromosome 1]. AB - Analysis of the nucleotide sequence of a cloned fragment of the human beta-casein gene was performed. A conserved DNA locus, present with a varying degree of degeneracy in introns of [beta]-casein genes of several species and in the intron of an oncogene of the sarc family, was revealed. It was located in region 1p31-32 by means of in situ hybridization. A clearly visible additional hybridization site was observed in region 1p36. The data obtained are discussed in the light of available information on several oncogenes that are located in region 1p3. A relation was found between this region and the occurrence of some cancers, including breast cancer. PMID- 8001799 TI - [Electrokinetic potential of Yersinia pestis and Escherichia coli cells with an intact or defective ycaA gene (caf1M) of the fra-operon of plague pathogen]. AB - The dependence of the amount of electrokinetic potential in cells of Escherichia coli and Yersinia pestis, which differ in the rate of reduction of lipopolysaccharide (LPS), on the presence or absence of typical and atypical capsules of Y. pestis, encoded by intact and mutant fra operons, respectively, was studied. The ycaA+ycaF+(caf1 M+caf1+) genotype was shown to be expressed in serological stability of a classical capsular antigen, irrespective of the producer strain, and a decrease in the negative charge of microbial cells compared to their noncapsular variants. Blocking of the synthesis of the product of the ycaA gene of the fra operon resulted in formation of encapsulated bacteria, whose surface electricity and serological characters varied in dependence on the LPS structure. Data obtained support the assumption that a product of the ycA gene stabilizes the conformation of the typical capsule of the plague-causing agent, which was formed from YcaF (Caf1) monomers. PMID- 8001796 TI - The mec-8 gene of Caenorhabditis elegans affects muscle and sensory neuron function and interacts with three other genes: unc-52, smu-1 and smu-2. AB - Mutations in the Caenorhabditis elegans gene mec-8 were previously shown to cause defects in mechanosensation and in the structure and dye filling of certain chemosensory neurons. Using noncomplementation screens, we have identified eight new mec-8 alleles and a deficiency that uncovers the locus. Strong mec-8 mutants exhibit an incompletely penetrant cold-sensitive embryonic and larval arrest, which we have correlated with defects in the attachment of body muscle to the hypodermis and cuticle. Mutations in mec-8 strongly enhance the mutant phenotype of unc-52(viable) mutations; double mutants exhibit an unconditional arrest and paralysis at the twofold stage of embryonic elongation, a phenotype characteristic of lethal alleles of unc-52, a gene previously shown to encode a homolog of the core protein of heparan sulfate proteoglycan, found in basement membrane, and to be involved in the anchorage of myofilament lattice to the muscle cell membrane. We have identified and characterized four extragenic recessive suppressors of a mec-8; unc-52(viable) synthetic lethality. The suppressors, which define the genes smu-1 and smu-2, can weakly suppress all mec 8 mutant phenes. They also suppress the muscular dystrophy conferred by an unc 52(viable) mutation. PMID- 8001800 TI - [Decrease in the level of DeoR-dependent repression of the deo operon as a result of integration of foreign DNA fragments into the interoperator deoO1-deoO2 region of the Escherichia coli chromosome]. AB - Two heterologous DNA fragments encoding the genes Kanr and cat were integrated into the regulatory region of the deo operon of Escherichia coli, located in a recombinant plasmid. As a result, plasmids pD5K and pD5C were obtained, in which the distance between the deoO1 and deoO2 operators increased from 599 bp in the deo operon of the wild type to 2019 and 1398 bp in case of integration of Kanr and cat, respectively. Then, linearized DNA of plasmids pD5K and pD5C was incorporated into the deo locus of the chromosome of E. coli through homologous recombination by the use of a recipient strain recBC sbcB. The constructed strains contained insertions in the interoperator region of the deo operon. Expression of the deo operon was studied in these strains, on a different genetic background with respect to the genes deoR, cytR, and cyaA. An increase in the interoperator distance was shown to increase the basal level of gene expression of the deo operon and to disturb cooperative interaction of the DeoR repressor and operator sites. PMID- 8001801 TI - [Analysis of maintenance of redundant genetic structures in the yeast Saccharomyces cerevisiae: disomy and spontaneous mitochondrial rho(-) mutability]. AB - With the postmeiotic progeny of triploids used as initial material, n + 1 disomics at chromosomes II, III, VII, VIII, and X were isolated. Disomy at the chromosomes listed (as well as for chromosomes IV and XIV, as demonstrated previously) is associated with decreased spontaneous rho- mitochondrial mutability. This suggests that a disturbance of the chromosome balance itself as such can lead to considerable changes in the spontaneous variability of the mitochondrial genome. From crosses between n + 1 disomics at chromosome IV and for each of the remaining above-mentioned six chromosomes, double n + 2 disomics were isolated, carrying nonchromologous pairs of extra chromosomes. Analysis of mitotic stability of the chromosome IV and spontaneous rho- mutability in double disomics shows that the effect of disomy on spontaneous rho- mutability most probably cannot be explained by direct competition between different genetic structures maintained in Saccharomyces cerevisiae cells. Disturbance of the chromosome balance in disomy is accompanied by essential qualitative changes in processes mediating the maintenance of genetic structures in yeast cells. PMID- 8001802 TI - [Isolation and characterization of new nuclear srm gene mutation causing coordinated changes in the maintenance of nuclear and mitochondrial genetic structures in the yeast Saccharomyces]. AB - From grown cultures of UV-irradiated Saccharomyces cerevisiae cells with disomy at chromosome IV, clones with nuclear gene mutations were isolated, each of which was suggested to change both mitochondrial spontaneous rho- mutability and the mitotic stability of extra natural chromosomes. Four such nonallelic mutations (srm8, srm12, srm15, and srm17) were isolated, and their phenotypic expression characterized. All four mutations are associated with decreased spontaneous rho- mutability and virtually block sporulation in homozygous mutant diploids. Mutation srm8 is temperature-sensitive and, most probably, involves an essential gene. Double mutants of genotypes srm8 cdc28-srm and srm8 srm12 are nonviable. Mutation srm12 increases the rate of spontaneous loss of extra chromosome XIV by disomics by a factor of about 30. Mutation srm15 induces a small (about twofold) but statistically significant decrease of this rate. Mutations srm8 and srm17 drastically decelerate reproduction of cells with disomy, which prevents quantitative estimations of rates of loss of extra chromosomes. PMID- 8001803 TI - [Restriction analysis of the mitochondrial genome of Salmonid fishes of the family Salmonidae]. AB - Based on comparative restriction analysis of mitochondrial DNA, genetic divergence between 11 species belonging to four genera of the family Salmonidae was estimated. About 2% of the mitochondrial genome (304 np) was examined using 16 restrictases that recognize 6-nucleotide sites. Nucleotide difference estimates ranged from 0-5.17 +/- 1.07% in chars of the genus Salvelinus to 2.05 +/- 0.71%-8.64 +/- 1.14% in the Pacific salmon species of the genus Oncorhynchus. The greatest divergence was found between the genera Oncorhynchus and Parahucho (9.42 +/- 1.31%-13.08 +/- 1.24%), and between Oncorhynchus and Salvelinus (12.50 +/- 1.00%). The divergence between the Pacific salmon and trout species was equal to 8.17 +/- 1.17. The generic status of Parahucho and Parasalmo is confirmed. PMID- 8001804 TI - [Analysis of recessive sex-linked lethal mutations in genotypically different strains of Drosophila melanogaster MS and w, exposed in the 5-kilometer zone of the accident at the Chernobyl nuclear reactor]. AB - The frequency of induced and spontaneous recessive sex-linked lethal mutations (RSLLM) in Drosophila melanogaster strains w and ms was estimated after their chronic irradiation in the five-kilometer zone of the Chernobyl' meltdown. The mutagenic effect of relatively low radiation doses was analyzed. In an experiment conducted in 1990, a significant increase in the RSLLM frequency was recorded, while, in 1991, no significant difference between the experiment and control was found. PMID- 8001805 TI - [Analysis of dominant and recessive sex-linked lethal mutations induced by low radiation doses in genetically different strains of Drosophila melanogaster w and MS]. AB - Frequencies of induced recessive sex-linked lethal mutations (RSLLM) and dominant lethal mutations (DLM) were analyzed in genetically different Drosophila melanogaster strains w and ms after their exposure to radiation on radioactive soil in laboratory conditions. The RSLLM test applied to males after their 14-day radiation exposure yielded controversial results. An analysis of induced and spontaneous DLM demonstrated an increase in the frequency of early embryonic lethal mutations in the experiment (radiation exposure) in comparison with the control (spontaneous mutation rate) in both strains examined. PMID- 8001806 TI - [Frequency of chromosome aberrations induced by stress and cyclophosphane in bone marrow cells of rats selected for the threshold of nervous system excitability]. AB - The frequency of chromosomal aberrations in bone marrow cells under the effect of long-term stress and cyclophosphamide was studied in rat lines selected for different levels of nervous system excitability. After both kinds of treatment, differences between lines in frequencies of chromosomal aberrations were observed. Stress had a weak mutagenic effect on rats with a low level of excitability, but no such effect on highly excitable rats. Correlations between cytogenetic parameters of chromosomal aberrations induced by cyclophosphamide and the functional state of the nervous system were ambiguous. Thus, the frequency of single and paired chromosome fragments did not show any apparent correlation with the excitability of animals. The frequency of translocation-like chromosomal interchanges in highly excitable rats was higher than in weakly excitable rats. In terms of the number of cells with aberrations, a dependence of the type of interlinear differences on the selection program was observed. Possible mechanisms responsible for differences in susceptibility of animals to the action of mutagenic factors are discussed in relation to peculiarities of the functional state of the nervous system in the studied lines. PMID- 8001807 TI - [Frequency distribution of HLA antigens and haplotypes in newly arrived inhabitants of Magadan]. AB - Peculiarities of the frequency distribution of antigens and haplotypes of A, B, and Cw subloci of the HLA system in 924 Slavic inhabitants of Magadan are described. Significant differences in gene and haplotype frequencies between inhabitants of Magadan and those of Moscow, Odessa, Poles'e, Latvia, and England were revealed, which could not be attributed solely to the specificity of migration processes. On the basis of an analysis of gamete associations of the A and B subloci, an attempt was made to explain the specificity of the frequency distribution of HLA system alleles and haplotypes in the investigated sample from an ecological point of view. PMID- 8001808 TI - [Incidence of developmental defects in human embryos in the territory of Byelarus after the accident at the Chernobyl nuclear power station]. AB - The incidence of developmental abnormalities (DA) among 5 to 12-week human embryos collected in Minsk during abortions before the Chernobyl' accident was compared to that in Minsk, Mogilev, and southeastern districts of Gomel' and Mogilev regions before and after the accident. The incidence of DA among human embryos from the most radionuclide-contaminated rural regions of Byelarus exceeds that of the control group and of the urban population after the Chernobyl' accident by a factor of 1.5-2. The mutagenic effect of irradiation is the most probable cause of the increased DA frequency. These data suggest that recording of DA in embryos obtained by medical abortions is a new promising approach to the monitoring of genetic consequences of irradiation in human populations. PMID- 8001809 TI - [Distribution of haptoglobin genotypes among persons subjected to chronic occupational irradiation in significant doses]. AB - Haptoglobin (Hp) genotype distribution was studied on 508 individuals from 52 to 78 years of age exposed 35-40 years ago to occupational chronic irradiation at doses considerably exceeding the maximally allowable level. Essential and noncoinciding changes in Hp genotype distribution were found among individuals who were exposed to total doses of external chi-irradiation exceeding 500 cGy or with 239-Pu incorporation exceeding 7.4 kBq. Irradiation-induced changes differed from age-dependent shifts in genotype distribution. It was suggested that variation of mortality from malignancies among individuals with different Hp genotypes might be the cause of these changes. PMID- 8001810 TI - Phaseolin nucleotide sequence diversity in Phaseolus. I. Intraspecific diversity in Phaseolus vulgaris. AB - Most information about the molecular biology of phaseolin, the major seed storage protein in Phaseolus vulgaris, has been obtained from the T-type phaseolin, which is characteristic of the Andean gene pool of the species. In the work reported here, two cDNA clones for the S-type phaseolin representing the other major, Middle American gene pool were isolated and sequenced. Analysis of the DNA sequences revealed the presence of two subtypes of S phaseolin, alpha and beta, depending on the presence or absence, respectively, of a 27-bp direct repeat. These are similar to the alpha- and beta-phaseolin subtypes found in the Andean, T phaseolin; however, the additional 15-bp direct repeat also found in the T alpha-phaseolin gene type was apparently absent from the S alpha-phaseolin genes. The overall sequence identity was greater between the alpha or beta subtypes of different gene pools than between the alpha or beta subtypes within gene pools. This implies that the gene subtypes were formed prior to the formation of the two major gene pools of P. vulgaris. Analysis of the putative amino acid sequence revealed that both the 'Sanilac' phaseolin subtypes contained an additional methionine, however, not at the same site. This opens the possibility of increasing the nutritionally limiting methionine level in phaseolin either through protein engineering or by screening accessions for recombinant phaseolin sequences that combine both substitutions. PMID- 8001811 TI - Genetic mapping and variability of seven soybean simple sequence repeat loci. AB - Microsatellites or simple sequence repeats are stretches of short tandemly repeated DNA sequence motifs, dispersed throughout the genomes of most eukaryotes. Simple sequence repeat polymorphisms (SSRPs) have recently been reported in plants. Here we present the genetic map position of seven different soybean (Glycine max (L.) Merr. and Glycine soja Sieb. and Zucc.) SSRPs contained in sequenced genes, four of which represent newly mapped positions for these genes. The other three SSRPs coincided with independently established RFLP map positions for the corresponding genes. When a set of 61 soybean accessions was screened at four of these loci by using agarose gels, the average number of alleles per locus was 7.75, the effective number of alleles (ne) was 2.57, and the level of allele differentiation (delta(t)) was 0.62. Allelic variation decreased sharply with increasing levels of domestication, with the level of differentiation going from 84% in the wild soybean to 43% in the elite germplasm. Variation levels observed on a subset made of 19 of the 61 lines were always higher for SSRPs than for RFLP markers, with the average number of alleles per locus going from 4.25 to 2.15. In comparison with RFLP markers, SSRPs are more informative and are easier to analyse but require more effort to develop. PMID- 8001812 TI - Microsatellite polymorphism in Dioscorea tokoro, a wild yam species. AB - Six microsatellite loci were characterized in Dioscorea tokoro, a wild yam species in East Asia. All six loci were polymorphic in a sample of 23 individuals from natural populations in Japan. The microsatellite loci displayed many alleles (6.2 alleles per locus on average), and the observed heterozygosity (Ho = 0.54) as well as expected heterozygosity (He = 0.68) were high. The heterozygosities were far more than that previously detected by allozyme analysis of D. tokoro (Ho = 0.23, He = 0.28). Five microsatellite loci were sufficient to provide a paternity exclusion rate (Q) of Q = 0.98, which enables monitoring of the pollen mediated gene flow between plants in a population. Microsatellite loci are abundant and highly polymorphic in D. tokoro and other plants and are therefore ideal markers for plant population genetic studies. PMID- 8001813 TI - Synaptonemal complex analysis of domestic sheep (Ovis aries) with Robertsonian translocations. III. Deficient pairing and NOR role in Massey III heterozygotes. AB - Spermatocytes from rams heterozygous for Massey translocation III (t(3)7;25) contained one trivalent and those from the rams heterozygous for both Massey translocations I and III (t1t3) contained two trivalents. Where two trivalents and the XY pair are present in the same nucleus they may form a synaptonemal complex (SC), but no SC segment is found between the two trivalents. The frequency of pairing abnormality in four t3 rams and two t1t3 rams did not significantly differ from that in the normal sheep, but t3 trivalents with diverse abnormal configurations were recorded. A hypothesis was proposed that nucleolar organizer regions (NORs) or nucleoli could account for deficient pairing behaviour and hence chromosome rearrangement, because the NOR region on an NOR-bearing chromosome was usually delayed in pairing, and unpaired regions tended to associate with other unpaired axes or SCs. PMID- 8001814 TI - Comparison of the neuralized genes of Drosophila virilis and D. melanogaster. AB - The neurogenic gene neuralized of Drosophila melanogaster is thought to play a role in the determination of cell fate in the embryonic nervous system as well as other tissues during development. To determine which sequences within the neuralized gene encode functionally important domains, we have initiated an interspecific comparison of the neuralized gene of D. virilis and D. melanogaster. In this study we show that several motifs that we have previously identified in the neuralized protein of D. melanogaster are conserved in D. virilis. These include a putative nuclear localization signal, a homeodomain similarity region, and a zinc finger motif. In contrast, a helix-turn-helix motif with structural similarity to those identified as DNA-binding regions of bacterial repressors is deleted. These results demonstrate that it is possible to identify key functional regions of the neuralized protein by an interspecific comparison. PMID- 8001815 TI - Mitochondrial DNA diversity in the pea aphid Acyrthosiphon pisum. AB - The pea aphid Acyrthosiphon pisum has been established in North America for at least a century and occurs on a broad range of host plants. Despite its importance as a crop pest, there is little understanding of the genetic structure of its populations or the extent of genetic divergence associated with different host plant utilization. This study examined the extent of mitochondrial DNA (mtDNA) diversity among 35 clones of pea aphids from alfalfa. Polymorphisms were detected at only 2 of 126 restriction sites, suggesting the same impoverished level of genetic diversity found in prior allozyme studies. However, length variation was common and apparently arose as a result of tandem repeats in two regions of the mtDNA molecule. Region 1 occurred in proximity to the control region of the molecule, while region 2 was close to a cluster of tRNA genes flanking the NAD-dehydrogenase subunit 3 gene on the opposite side of the mtDNA molecule. Each of the aphid clones was homoplasmic for a single length variant in region 1, which varied with respect to the number of copies of a 120-bp repeat. By contrast, one-third of the clones were heteroplasmic at region 2, where they possessed a variable number of copies of a 210-bp repeat. Reanalysis of clones after 30 generations of parthenogenetic reproduction established the stability of length variants over this interval, suggesting their value in studies of the genetic structure of aphid populations. PMID- 8001816 TI - Growth suppression by p18, a p16INK4/MTS1- and p14INK4B/MTS2-related CDK6 inhibitor, correlates with wild-type pRb function. AB - The D-type cyclin-dependent kinases CDK4 and CDK6 are complexed with many small cellular proteins (p14, p15, p16, p18, and p20). We have isolated cDNA sequences corresponding to the MTS2 genomic fragment that encodes the CDK4- and CDK6 associated p14 protein. By use of a yeast interaction screen to search for CDK6 interacting proteins, we have also identified an 18-kD human protein, p18, that is a homolog of the cyclin D-CDK4 inhibitors p16 (INK4A/MTS1) and p14 (MTS2/INK4B). Both in vivo and in vitro, p18 interacts strongly with CDK6, weakly with CDK4, and exhibits no detectable interaction with the other known CDKs. Recombinant p18 inhibits the kinase activity of cyclin D-CDK6. Distinct from the p21/p27 family of CDK inhibitors that form ternary complexes with cyclin-CDKs, only binary complexes of p14, p16, and p18 were found in association with CDK4 and/or CDK6. Ectopic expression of p18 or p16 suppresses cell growth with a correlated dependence on endogenous wild-type pRb. PMID- 8001817 TI - Loss of the imprinted IGF2/cation-independent mannose 6-phosphate receptor results in fetal overgrowth and perinatal lethality. AB - Murine embryos that inherit a nonfunctional insulin-like growth factor-II/cation independent mannose 6-phosphate receptor (Igf2r) gene from their fathers are viable and develop normally into adults. However, the majority of mice inheriting the same mutated allele from their mothers die around birth, as a consequence of major cardiac abnormalities. These mice do not express IGF2R in their tissues, are 25-30% larger than their normal siblings, have elevated levels of circulating IGF2 and IGF-binding proteins, and exhibit a slight kink in their tails. These results show that Igf2r is paternally imprinted and reveal that the receptor is crucial for regulating normal fetal growth, circulating levels of IGF2, and heart development. PMID- 8001818 TI - Elements of a single MAP kinase cascade in Saccharomyces cerevisiae mediate two developmental programs in the same cell type: mating and invasive growth. AB - Diploid Saccharomyces cerevisiae strains starved for nitrogen undergo a developmental transition from a colonial form of growth to a filamentous pseudohyphal form. This dimorphism requires a polar budding pattern and elements of the MAP kinase signal transduction pathway essential for mating pheromone response in haploids. We report here that haploid strains exhibit an invasive growth behavior with many similarities to pseudohyphal development, including filament formation and agar penetration. Haploid filament formation depends on a switch from an axial to a bipolar mode of bud site selection. Filament formation is distinct from agar penetration in both haploids and diploids. We find that the same components of the MAP kinase cascade necessary for diploid pseudohyphal development (STE20, STE11, STE7, and STE12) are also required for both filament formation and agar penetration in haploids. Thus, haploid yeast cells can enter either of two developmental pathways: mating or invasive growth, both of which depend on elements of a single MAP kinase cascade. Our results provide a novel developmental model to study the dynamics of signal transduction, with implications for higher eukaryotes. PMID- 8001819 TI - JNK2 contains a specificity-determining region responsible for efficient c-Jun binding and phosphorylation. AB - The transcriptional activity of c-Jun is augmented through phosphorylation at two sites by a c-Jun amino-terminal kinase (JNK). All cells express two distinct JNK activities, 46 and 55 kD in size. It is not clear which of them is the more important c-Jun kinase and how they specifically recognize c-Jun. The 46-kD form of JNK was identified as a new member of the MAP kinase group of signal transducing enzymes, JNK1. Here, we report the molecular cloning of the 55-kD form of JNK, JNK2, which exhibits 83% identity and similar regulation to JNK1. Despite this close similarity, the two JNKs differ greatly in their ability to interact with c-Jun. JNK2 binds c-Jun approximately 25 times more efficiently than JNK1, and as a result has a lower Km toward c-Jun than JNK1. The structural basis for this difference was investigated and traced to a small beta-strand-like region near the catalytic pocket of the enzyme. Modeling suggests that this region is solvent exposed and therefore is likely to serve as a docking site that increases the effective concentration of c-Jun near JNK2. These results explain how two closely related MAP kinases can differ in their ability to recognize specific substrates and thereby elicit different biological responses. PMID- 8001820 TI - Dynamic association of proteins with the pre-mRNA branch region. AB - The association of proteins with the branch site region during pre-mRNA splicing was probed using a novel methodology to site-specifically modify the pre-mRNA with the photo-reagent benzophenone. Three sets of proteins were distinguished by the kinetics of their associations with pre-mRNAs, by their association with discrete splicing complexes, and by their differing factor requirements. An early U1 snRNP-dependent cross-link of the branch region to a p80 species was followed by cross-links to p14, p35, and p150 polypeptides associated with the U2 snRNP pre-mRNA complex. Concomitant with formation of the spliceosome, a rearrangement of protein factors about the branch region occurred, in which the p35 and p150 cross-links were replaced by p220 and p70 species. These results establish that the branch region is recognized in a dynamic fashion by multiple distinct proteins during the course of spliceosomal assembly. PMID- 8001821 TI - Ribonuclease E provides substrates for ribonuclease P-dependent processing of a polycistronic mRNA. AB - The polycistronic mRNA of the histidine operon is subject to a processing event that generates a rather stable transcript encompassing the five distal cistrons. The molecular mechanisms by which such a transcript is produced were investigated in Escherichia coli strains carrying mutations in several genes for exo- and endonucleases. The experimental approach made use of S1 nuclease protection assays on in vivo synthesized transcripts, site-directed mutagenesis and construction of chimeric plasmids, dissection of the processing reaction by RNA mobility retardation experiments, and in vitro RNA degradation assays with cellular extracts. We have found that processing requires (1) a functional endonuclease E; (2) target site(s) for this activity in the RNA region upstream of the 5' end of the processed transcript that can be substituted by another well characterized rne-dependent cleavage site; (3) efficient translation initiation of the first cistron immediately downstream of the 5' end; and (4) a functional endonuclease P that seems to act on the processing products generated by ribonuclease E. This is the first evidence that ribonuclease P, an essential ribozyme required for the biosynthesis of tRNA, may also be involved in the segmental stabilization of a mRNA. PMID- 8001822 TI - fgfr-1 is required for embryonic growth and mesodermal patterning during mouse gastrulation. AB - Experiments in amphibians have implicated fibroblast growth factors (FGFs) in the generation and patterning of mesoderm during embryogenesis. We have mutated the gene for fibroblast growth factor receptor 1 (fgfr-1) in the mouse to genetically dissect the role of FGF signaling during development. In the absence of fgfr-1 signaling, embryos displayed early growth defects; however, they remained capable of gastrulating and generating mesoderm. The nascent mesoderm of fgfr-1 homozygous mutant embryos differentiated into diverse mesodermal subtypes, but mesodermal patterning was aberrant. Somites were never generated and axial mesoderm was greatly expanded at the expense of paraxial mesoderm. These results suggest that FGFR-1 transduces signals that specify mesodermal cell fates and regional patterning of the mesoderm during gastrulation. PMID- 8001823 TI - Murine FGFR-1 is required for early postimplantation growth and axial organization. AB - We have explored the role of fibroblast growth factor receptor 1 (FGFR-1) in early embryonic development using three experimental systems: genetically deficient mice, in vitro blastocyst culture, and FGFR-1-deficient embryonic stem cells. Using these systems, we demonstrate that FGFR-1 is required for proper embryonic cell proliferation and for the correct axial organization of early postimplantation embryos but not for mesoderm formation. FGFR-1-deficient embryos display severe growth retardation both in vitro and in vivo and die prior to or during gastrulation. Although these mutants can form nonaxial tissues, such as the allantois, amnion, and yolk sac mesoderm, they display defective patterning of the primitive streak and other axial structures, and frequently exhibit truncations or disorganization of posterior embryonic regions. Such abnormalities are unlikely to be caused by intrinsic blocks in mesodermal differentiation, as FGFR-1-deficient ES cell lines form teratomas consisting of many mesodermal cell types. PMID- 8001824 TI - Location, structure, and function of the target of a transcriptional activator protein. AB - We have isolated and characterized single-amino-acid substitution mutants of RNA polymerase alpha subunit defective in CAP-dependent transcription at the lac promoter but not defective in CAP-independent transcription. Our results establish that (1) amino acids 258-265 of alpha constitute an "activation target" essential for CAP-dependent transcription at the lac promoter but not essential for CAP-independent transcription, (2) amino acid 261 is the most critical amino acid of the activation target, (3) amino acid 261 is distinct from the determinants for alpha-DNA interaction, and (4) the activation target may fold as a surface amphipathic alpha-helix. We propose a model for transcriptional activation at the lac promoter that integrates these and other recent results regarding transcriptional activation and RNA polymerase structure and function. PMID- 8001825 TI - Retinoid-dependent in vitro transcription mediated by the RXR/RAR heterodimer. AB - The effects of retinoids on gene regulation are mediated by retinoic acid receptors (RARs) and retinoid X receptors (RXRs). Here, we provide the first biochemical evidence that, in vitro, ligand governs the transcriptional activity of RXR alpha/RAR alpha by inducing conformational changes in the ligand-binding domains. Using limited proteolytic digestion we show that binding of the cognate ligand causes a conformational change in the carboxy-terminal part of the receptor. We also show that recombinant RXR alpha/RAR alpha is partially active in the absence of exogenously added ligand. Trans-activation depends critically on the ligand-dependent transcriptional activation function AF-2 of RAR alpha. Full activation by recombinant RXR alpha/RAR alpha, however, requires the addition of either all-trans RA, 9-cis RA, or other RAR-specific agonists, whereas an RAR alpha-specific antagonist abolishes trans-activation. Intriguingly, the ligand-dependent AF-2 of RXR does not contribute to the level of transcription from the RAR beta 2 promoter in vitro even when the cognate ligand (9-cis RA) is bound. Thus, the major role of RXR in trans-activation of the RAR beta 2 promoter is to serve as an auxiliary factor required for the binding of RAR which, in turn, is directly responsible for transcriptional activity. PMID- 8001826 TI - Galactose-containing glycoconjugates of the ciliary body and lens in capsular glaucoma: a lectin histochemical study. AB - BACKGROUND: This study was carried out in order to obtain information on galactose-containing glycoconjugates in the lens and ciliary body of human eyes with capsular glaucoma and thus on the etiopathogenesis of exfoliation syndrome. METHODS: Six formalin-fixed, paraffin-embedded human eyes with capsular glaucoma and six control eyes were studied using a panel of 11 biotinylated lectins with extended binding sites to galactose- and N-acetylgalactosamine-containing glycoconjugates. Both pepsin and neuraminidase pretreatments were performed. RESULTS: Gal(beta 1-->3)GalNAc-reactive peanut (PNA) and Bauhinia purpurea alba (BPA) agglutinins and Gal(beta 1-->4)GlcNAc GlcNAc-reactive Ricinus communis (RCA I) and Phaseolus vulgaris (PHA-E) agglutinins reacted strongly with exfoliation material, while binding of Gal(beta 1-->4)GlcNAc-reactive Erythrina cristagalli and GalNAc-reactive soybean, Caragana arborescens, Vicia villosa, Helix pomatia (HPA) and Dolichos biflorus agglutinins was generally weak. In the nonpigmented ciliary epithelium and on the zonular fibers and lamella, at least moderate reaction was detected with PNA, BPA, RCA-I and PHA-E, and these tissues thus resembled exfoliation material in their reactivity. In contrast, the lens epithelium reacted weakly with PHA-E and HPA only, and the lens capsule was never labeled. No qualitative changes were seen after neuraminidase pretreatment. CONCLUSION: The findings suggest that galactose- and N-acetylgalactosamine containing glycoconjugates in exfoliation material are at least partially produced by the nonpigmented ciliary epithelium, rather than by the lens epithelium. Moreover, PNA, PBA, RCA-I and PHA-E seem to be the most suitable of the lectins tested for detection of exfoliation material in histological specimens. PMID- 8001827 TI - Effect of levodopa on the human dark adaptation threshold. AB - BACKGROUND: In several species there is strong evidence that the retinal dopamine turnover is influenced by retinal dark and light adaptation. In the human retina, dopamine has been found in amacrine and interplexiform cells. METHODS: In the present study, the influence of orally administered levodopa on the human dark adaptation was investigated in healthy subjects using the Goldmann-Weekers adaptometer. To exclude effects of levodopa on the pupil size, a second group was examined after pupil dilation before each examination. A third and fourth group were examined under the same conditions as the first two groups, but without levodopa administration. RESULTS: Levodopa caused a uniform threshold elevation throughout dark adaptation with undilated and dilated pupils. No effect on sensitivity was observed in the control groups. CONCLUSION: These results show a dopaminergic reduction in sensitivity during human dark adaptation. PMID- 8001828 TI - HLA antigens in a Japanese family with Behcet's disease. AB - BACKGROUND: Familial Behcet's disease is rare. METHODS: HLA antigens in a Japanese family with Behcet's disease were examined. RESULTS: The affected patients had HLA B51, and unaffected family members also had the same antigen. CONCLUSION: It is likely that not only HLA B51 but also other factors may be involved in the pathogenesis of Behcet's disease in Japanese patients. PMID- 8001829 TI - Patch culturing and transfer of human fetal retinal epithelium. AB - Human retinal pigmented epithelium (RPE) can be cultured by removing small patches of this layer from the choroid of the fetal eye. Such RPE patches give rise to healthy, epithelioid monolayers in vitro within 1-2 weeks without contamination from retinal or choroidal cells. The viability and proliferative capacity of these cultures is independent of the initial polarity of the patch. These RPE monolayers develop apical/basal polarity and a basal lamina and rest on a field of collagen fibers; they are capable of phagocytizing outer segments. A patch can be lifted off a confluent monolayer and transferred to another culture dish without risking the viability of either the old or the new culture. This provides a means of transplanting an organized, polarized patch of human RPE from one place to another. PMID- 8001830 TI - Hydrolase participation in allograft rejection in rat penetrating keratoplasty. AB - BACKGROUND: A rat model of orthotopic corneal graft rejection was used to investigate the alterations in hydrolase activity within the corneal graft or within cellular infiltrates during acute rejection. METHODS: The distribution of the lysosomal enzymes [acid phosphatase (AP), N-acetyl-beta-D-glucosaminidase (NAG), beta-glucuronidase (beta-Gluc), beta-galactosidase (beta-Gal), dipeptidylpeptidase II (DPPII)] and of the membrane-bound proteases [aminopeptidase M (APM), aminopeptidase A (APA), gamma-glutamyltransferase (GGT), alkaline phosphatase (ALP), dipeptidylpeptidase IV (DP-PIV)] were investigated by histochemical methods in the grafts at 3, 5, 8, 10 and 12 days following allogeneic transplantation. Serial sections of the grafts were also examined for RT1b, CD4, CD4+, CD8, CD11b/c and CD45, in order to determine hydrolase activity within infiltrating cells. RESULTS: Allogeneic grafts were invaded by macrophages, CD4- and CD8-positive lymphocytes. In contrast, syngeneic grafts, performed as a control, contained occasional lymphocytes and focal aggregations of macrophages around suture sites. The allogeneic cellular infiltrate stained intensely for AP and ALP; moderately for beta-Gluc, NAG and beta-Gal; and mildly for GGT, DPPII and APM in grafts at all postoperative times. Serial sectioning indicated that the majority of the lysosomal hydrolases were located in macrophages; AP, APM and GGT were, however, observed in lymphocytes. Vessel ingrowth could be observed with enzyme staining for AP, beta-Gluc, NAG, ALP, APA and APM. Hydrolase activity in the corneal endothelium served as an indicator of endothelial function during the rejection process. CONCLUSION: Changes in normal hydrolase activities in corneal grafts in the rat model indicate decreasing corneal function during the rejection process. Hydrolases released from infiltrating cells contribute to the morphological disruption and, possibly, to graft rejection. PMID- 8001831 TI - Leflunomide therapy following penetrating keratoplasty in the rat. AB - BACKGROUND: The isoxal derivative, leflunomide (LF), is a new potent immunosuppressive which has been shown to be effective in preventing autoimmune disorders and reactions leading to organ transplantation rejection. LF is thought to antagonise cytokine activity and thereby to interfere with T-helper-cell dependent B- and T-lymphocyte proliferation. METHODS: We used LF to treat corneal allograft rejection in the rat, comparing its effect with that of cyclosporin A (CSA). Corneal buttons were grafted from Lewis/Brown Norway rats to Lewis recipients. Animals were randomly assigned to the following treatment groups: I, untreated; II, CSA (10 mg/kg i.m.); III, LF (2.5 mg/kg p.o.); IV, LF (5 mg/kg p.o.); V, LF (10 mg/kg p.o.); VI, combined therapy (LF 10 mg/kg p.o. and CSA 10 mg/kg i.m). Treatment began on the first postoperative day and was continued until rejection occurred. RESULTS: The mean graft rejection time in the untreated allogeneic group was 12 days. A significant delay in graft rejection was observed in all treatment groups compared with group I (P < 0.001). Further, the delay in graft rejection resulting from combined therapy (group VI) was statistically significant compared with all other groups (P < 0.001). CONCLUSION: These results suggest that (a) LF when used alone is as effective as CSA in treating corneal allograft rejection in the rat, and (b) when LF and CSA are combined they are more effective than either drug alone in the prolongation of allograft survival. PMID- 8001832 TI - Histological and immunopathological analysis of T-cells mediating murine HSV-1 keratitis. AB - BACKGROUND: Thymus-derived lymphocytes play a critical role in the development of herpes simplex keratitis (HSK). T-cell subsets defined by their expression of various T-cell receptor (TCR) V beta segments were studied following corneal HSV 1 infection (p.i.). METHODS: Conjunctiva, corneal limbus and corneal stroma of two inbred BALB/c congenic mouse strains which differ only in the gene products closely linked to the Igh-1 locus on chromosome 12 were analyzed. RESULTS: While C.B-17 mice (Igh-1b) were resistant to HSK, C.AL-20 mice (Igh-1d) clinically developed severe necrotizing keratitis by day 11 p.i. The corneal stroma of C.B 17 mice remained clear, while it was increasingly infiltrated by mononuclear cells and neutrophils in C.AL-20 mice by day 11 p.i. In C.B-17 mice, Thy1.2+ cells were found in the conjunctiva between days 2 to 4 p.i., and subsequently decreased. Only a few Thy1.2+ cells were found in the limbus, and no such cells were found in the stroma. In contrast, in C.AL-20 mice the numbers of Thy1.2+ cells (activated CD4+, V beta 8+ T cells) profoundly increased in the conjunctiva by day 4 p.i. These cells infiltrated the limbus between days 7 and 11 p.i. and eventually entered the stromal tissue by day 11 p.i. CONCLUSIONS: Our data suggest that the HSV-1-induced corneal tissue destruction is mediated by mononuclear cells and neutrophils and that these cells are probably attracted into the cornea by cytokines elaborated by activated CD4+, V beta 8+ T cells. PMID- 8001833 TI - Linoleic acid hydroperoxide-induced peroxidation of endothelial cell phospholipids and cytotoxicity. AB - Peroxidation of endothelial cell phospholipids was examined following treatments with linoleic acid hydroperoxide. The treatment effects were analyzed over a range of toxicities and exposure intervals as determined by cell plating efficiencies and survival. Over the concentration ranges where lipid peroxidation was evident (20-40 microM treatments in complete medium), significant cytotoxicity was apparent after 1 h of exposure. The extent of toxicity was dependent on the time interval between the end of peroxide treatment and replating of cells. Maximum toxicity was found when cells were replated 1-3 h after treatment. When cells were replated 4 h after treatment a linear increase in cell survival was found as a function of replating time following peroxide exposure. Analysis of cell phospholipids by HPLC after 1 h of exposure to linoleic acid hydroperoxide revealed that peroxidation (evidenced by conjugated diene content) had taken place among a number of phospholipid species with the most marked increases in phosphatidylcholine. Analysis of the fatty acyl composition of phospholipids also showed that the proportions of polyunsaturated fatty acids were reduced relative to saturated fatty acids, indicating peroxidative damage to phospholipids. Pretreatment of cells with vitamin E prevented the peroxidation of all phospholipids and blocked the cytotoxic action of linoleic acid hydroperoxide. These findings indicate that an immediate cytotoxic action of lipid hydroperoxide is associated with peroxidation of membrane phospholipids. This cytotoxicity is a transient effect, and cells surviving the acute injury display a time-dependent increase in plating efficiency representing a period of repair. PMID- 8001834 TI - Lipid hydroperoxide-induced peroxidation and turnover of endothelial cell phospholipids. AB - The effects of lipid peroxidation on rabbit aortic endothelial cell phospholipid turnover was studied using linoleic acid hydroperoxide (LOOH). Following treatments with 20-40 microM LOOH, cells prelabeled with either arachidonic acid (20:4) or oleic acid (18:1) showed a movement of these fatty acids out of the phospholipids and into neutral lipid and free fatty acid pools. There was also a release of radioactive free fatty acids and phospholipids into the media, which was significantly increased as compared to cells maintained under standard culture conditions. Fatty acid uptake and distribution among phospholipid pools was also affected by LOOH treatment where incorporation of 20:4 and 18:1 into phosphatidylcholine (PC) decreased, while uptake into phosphatidylinositol (PI) increased after 1 h of incubation with 40 microM LOOH. These effects were also inhibited by vitamin E. In cells prelabeled with 20:4 or 18:1 under conditions where approximately 99% of the fatty acids were incorporated into neutral and phospholipid pools, LOOH treatment produced a decrease in radioactivity associated with PC, while the specific activity of PI increased. The extent of these changes was greater for 20:4 than 18:1, but in each case the effects were inhibited by vitamin E. The temporal pattern of uptake for labeled choline and inositol after LOOH treatments paralleled those found for fatty acid incorporation. These cell responses indicate that induction of lipid peroxidation produces rapid fatty acid release and phospholipid turnover involving repair as well as de novo synthesis. The implications of these effects on turnover of specific phospholipids and cell responses to oxidative stress are discussed. PMID- 8001835 TI - Methoxatin (PQQ) in guinea-pig neutrophils. AB - PQQ, also called methoxatin, has been isolated from guinea-pig neutrophils. The organic cations diphenyleneiodonium (DPI) and diphenyliodonium (BPI) and the aromatic o-diamine 4,5-dimethylphenylenediamine (DIMPDA) sequester synthetic PQQ and inhibit its redox-cycling activity in a model system. Standards were made of adducts of tritiated PQQ with unlabeled DIMPDA and of unlabeled PQQ with tritiated DPI or DIMPDA. PQQ adducts were isolated from guinea-pig neutrophils with each of the tritiated inhibitors. They were separated and defined by high performance liquid chromatography (HPLC). Tiron, a disodium benzene disulphonic acid, broke the DPI-PQQ adduct isolated from neutrophils and released free PQQ. Both DPI and DIMPDA, as well as BPI, blocked O2.- release by stimulated neutrophils. The blockade exerted by these inhibitors was released by the addition of PQQ to the cell suspensions. The data demonstrate the presence of PQQ in guinea-pig neutrophils and suggest that it has a possible role, direct or indirect, in the O2.(-)-producing respiratory burst. PMID- 8001836 TI - Electron paramagnetic resonance investigations of free radical-induced alterations in neocortical synaptosomal membrane protein infrastructure. AB - Evidence is presented that free radical stress can directly induce physico chemical alterations in rodent neocortical synaptosomal membrane proteins. Synaptosomes were prepared from gerbil cortical brain tissue and incubated with 3 mM ascorbate and various concentrations of exogenous Fe2+ for 30-240 min at 37 degrees C. Synaptosomes were then lysed and covalently labeled with the protein thiol-selective spin label MAL-6 (2,2,6,6-tetramethyl-4-maleimidopiperdin-1-oxyl) and subjected to electron paramagnetic resonance (EPR) spectrometry. In separate experiments, synaptosomal membranes were labeled with the thiol-specific spin label MTS ((1-oxyl-2,2,5,5-tetramethyl-pyrroline-3-methyl)-methanethiosulfonate), or the lipid-specific spin probe 5-NS (5-nitroxide stearate). Free radical stress induced by iron/ascorbate treatment has a rigidizing effect on the protein infrastructure of these membranes, as appraised by EPR analysis of membrane protein-bound spin label, but no change was detected in the lipid component of the membrane. These results are discussed with reference to potential oxidative mechanisms in aging and neurological disorders. PMID- 8001837 TI - The redox couple between glutathione and ascorbic acid: a chemical and physiological perspective. AB - This article provides a comprehensive analysis of the redox reaction between glutathione/glutathione disulfide and ascorbic acid/dehydroascorbic acid. It includes an historical perspective of the progression of the experiments, first begun more than 60 years ago and continuing today with heightened importance. Indeed, the antioxidant capacity of glutathione and ascorbic acid, whether singly or in combination, linked via the redox couple, is a subject of intense interest for studies by bench scientists and clinicians, particularly because a growing body of evidence suggests that free radicals may be involved in a variety of diseases. The authors begin with a detailed summary of "test tube" experiments (the chemical perspective) that have revealed the conditions that regulate the rate of the redox coupling between glutathione and dehydroascorbic acid and that promote or inhibit the decomposition of dehydroascorbic acid in ordinary, buffered aqueous media; results obtained in the authors' laboratory are used for illustration purposes and uniformity of presentation. The authors then proceed to a critical examination of the extent to which the redox couple between glutathione and ascorbic acid operates in a cell, using the often published antioxidant cascade (See Fig. 1) as the model for the analysis (the physiological perspective). The evidence for and the evidence against the presence of the enzyme dehydroascorbate reductase in animal cells is outlined in a balanced way in an attempt to make sense of this continuing controversy. Next, the authors carefully document the many studies showing that exogenous dehydroascorbic acid is transported into cells where it is reduced to ascorbic acid by glutathione. Finally, they probe the functional significance and efficiency of the redox couple in monolayer cultures of human retinal pigment epithelial (RPE) cells, as a prototypical cellular model. The authors include the results of new experiments showing that incubation of RPE cells with a nitroxide, TEMPOL, leads to the selective oxidation of intracellular ascorbic acid. This approach is desirable because it dissects the cascade at a specific site and permits measurements of the levels of ascorbic acid and glutathione in the cells before, during, and after oxidation. The results show that only partial regeneration of ascorbic acid is obtained when control conditions are restored. However, if either ascorbic acid or dehydroascorbic acid is added to the media during the recovery period following treatment of cells with TEMPOL, then full recovery of ascorbic acid is observed.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8001838 TI - Characteristics of low molecular weight substances regulating plasma superoxide dismutase activity. AB - Low molecular weight peptides which inhibit both plasma and red cell superoxide dismutase (SOD) activity have been isolated from human plasma. Several fractions of the substance were isolated chromatographically. The most active peptides have molecular weight about 1000 and 5000 D. The peptide lowering the SOD activity accelerates the hemoglobin oxidation reaction by NaNO2 and diminishes the laboratory animals' period of life in the process of intoxication by NaNO2. Another peptide was also isolated from human plasma and increased the SOD activity. The work is in progress on purification of this substance and investigation of its physical properties. PMID- 8001839 TI - Superoxide anion production during monoelectronic reduction of xenobiotics by preparations of rat brain cortex, microvessels, and choroid plexus. AB - Brain microsomes may produce reactive metabolites during the reductive metabolism of some xenobiotics including drugs. These reactive species can, in turn, react with molecular oxygen to form superoxide radicals (O2.-). We measured the rates of superoxide production by homogenates obtained from three cerebral structures, cortex plus cerebellum, choroid plexus, and microvessels. The molecules assayed were related to quinone, nitroheterocycle, and iminium chemical families. The results we obtained showed a significant correlation between the rate of superoxide anion production and the apparent kinetic parameters (log Km/Vmax) of NADPH-cytochrome P450 reductase activity for these molecules, suggesting the involvement of this enzyme in xenobiotic-induced superoxide production. PMID- 8001840 TI - Spin trapping of superoxide in aqueous solutions of fresh and aged cigarette smoke. AB - Superoxide generation in aqueous solutions of cigarette smoke was determined as a function of the age of smoke using spin trapping. As a spin trap, 5,5 dimethylpyrroline-N-oxide (DMPO) was used. The superoxide adduct of DMPO was detected in a solution of fresh main-stream smoke for over 1 h. The superoxide generating potential of smoke was rapidly lost as the smoke was kept in a plastic syringe. The smoke that was aged for 3 min did not generate superoxide. Additional evidence of superoxide generation in aqueous solutions of cigarette smoke was obtained by the chemiluminescence method. PMID- 8001842 TI - [Nascentes morimur]. PMID- 8001841 TI - Is insulin resistance influenced by dietary linoleic acid and trans fatty acids? AB - The incidence of obesity, noninsulin-dependent diabetes mellitus (NIDDM), hypertension, and coronary artery disease has increased in the developed world. At the same time, major changes in the type and amount of fatty acid intake have occurred over the past 40-50 years, reflected in increases in saturated fat (from both animal sources and hydrogenated vegetable sources), trans fatty acids, vegetable oils rich in linoleic acid, and an overall decrease in long chain polyunsaturated fatty acids (arachidonic acid, eicosapentaenoic acid, and docosahexaenoic acid--C20-C22). Recent findings that C20-C22 in muscle membrane phospholipids are inversely related to insulin resistance, whereas linoleic acid is positively related to insulin resistance, suggest that diet may influence the development of insulin resistance in obesity, insulin-dependent diabetes mellitus (IDDM), hypertension, and coronary artery disease (including asymptomatic atherosclerosis and microvascular angina). These conditions are known to have genetic determinants and have a common abnormality in smooth muscle response and insulin resistance. It is proposed that the current diet influences the expression of insulin resistance in those who are genetically predisposed. Therefore, clinical investigations are needed to evaluate if lowering or preventing insulin resistance through diet by increasing arachidonic acid, eicosapentaenoic acid, and docosahexaenoic acid, while lowering linoleic acid and decreasing trans fatty acids from the diet, will modify or prevent the development of these diseases. PMID- 8001843 TI - [Influence of evening primrose oil on blood pressure and the pressor response to angiotensin II in pregnant and non-pregnant rabbits]. AB - Evening primrose oil was given through a intragastric catheter in dose of 50 mg/kg day for 10 days to pregnant (8 animals) and nonpregnant (8 animals) rabbits. Control groups contained 8 pregnant and 8 nonpregnant animals. In the acute experiment we estimated directly (intraarterially) basal blood pressure and pressor response to angiotensin II (A II). The systolic and diastolic response to A II was significantly lower in pregnant rabbits which received evening primrose oil compared to control group. No significant effect was found in the nonpregnant groups. Basal (before A II) systolic and diastolic blood pressure did not differ between the treated and untreated subject in each group. PMID- 8001844 TI - [New aspects in diagnosis and therapy of Turner's syndrome]. AB - In the last 35 years we noticed 91 cases of Turner's syndrome. To the obligatory symptoms of the syndrome belong primary amenorrhoea, sexual infantilism, elevated values only of FSH and very reduced levels of estrogens, chromosomal aberrations in karyotype, most often 45, X and presence of streak gonads. The facultative symptoms of the syndrome belong short stature (94.5% of patients), presence of congenital defects (short webbed neck in 44.4%) and sterility (98.9%). Therapy above 15 years excepting to cause the menstrual cycles have to development the second sexual symptoms by giving enough large doses of oestrogens and gestagens. The best effects we obtain nearly in 100% in the development of breasts, in slowly growth of sexual hair and in the growth of the stature which does not cross the height of 150 cm and only in six patients attained in average 152.5 cm. PMID- 8001845 TI - [HSG--usefulness in diagnosing infertility]. AB - HSG examination was performed on 363 female patients diagnosed because of infertility. In 258 (71.8%) women primary infertility was recognized and in 105 (28.9%) secondary infertility. Normal anatomical state of Fallopian tube was observed in 65 (77.4%) patients with primary infertility and only in 19 (22.6%) with secondary infertility. Abnormal results of examination were discovered in altogether 279 (76.9%) diagnosed patients. Taking into consideration Fallopian tube factor in secondary infertility, it was discovered in as many as 81.9% of cases. PMID- 8001846 TI - [Laparoscopic evaluation of small pelvic adhesions in female patients treated for infertility]. AB - The range and nature of adhesions found out by means of laparoscopy was analysed in patients diagnosed because of infertility. 38% of patients had laparotomy performed previously. Adhesions concerned 47% of the reproductive organ, although in nearly the same percentage intestine and greater omentum were involved. In 13 (31%) patients occurrence of endometriosis focus was discovered. In the area of Fallopian tube--ovary there were most often non-vascularized, thin adhesions and solid adhesions in the area of Douglas sinus. PMID- 8001847 TI - [Salpingitis and tubal pregnancy in patients treated at the first Clinic of Surgical Gynecology in Lublin between the years 1978-1988]. AB - Retrospective study was performed upon incidence of tubal pregnancy and histopathologically proved post-infection changes in oviducts. The incidence of tubal pregnancy was significantly decreasing in studied period in our institution despite the fact that salpingitis was found more often. Authors conclude that recently reported increase of tubal pregnancy is valid only in the populations studied and not in general. Relation between salpingitis and tubal pregnancy is not always evident. PMID- 8001848 TI - [Usefulness of CA-125 antigen for monitoring neoplastic processes in patients with ovarian tumors]. PMID- 8001849 TI - [Potentiometric determination of sodium and potassium in cervical mucus of women]. AB - The study was performed in 67 healthy women aged 24-38 (28.41 +/- 2.4) years, divided into two groups: group I (control) included 22 women with biphasic menstrual cycles, group II included 21 women with monophasic cycles. The concentration of sodium and potassium in cervical mucus was measured with ion selective electrodes. It was found that women with monophasic cycles had significantly (p < 0.001) lower levels of sodium than controls. PMID- 8001850 TI - [Small cell carcinoma of the ovary]. AB - Three cases of small cell carcinoma of the ovary are presented. Attention to diagnostic difficulties, extremely aggressive course and low sensitivity to oncologic treatment was paid. PMID- 8001851 TI - [Brain neoplasms in pregnancy. Two case histories]. AB - The diagnosis of brain tumor in a pregnant women is a dramatic event. The nature and timing of therapy at intracranial neoplasm are affected by the existence of the pregnancy. The authors report a two cases of cerebral neoplasm in pregnancy. Clinical syndromes, diagnosis, neurosurgical and obstetrical management are discussed. PMID- 8001852 TI - [Vesico-uterine fistula as a complication after the second cesarean section]. AB - The case of vesico-uterine fistula after second Cesarean section is presented. The diagnosis was based on history data, urine examination, histerosalpingography and cystoscopy. Transvesical fistulectomy with good results was performed 6 month after Cesarean section. PMID- 8001853 TI - [Report form the ESHRE '93 Congress]. PMID- 8001854 TI - [Predictive value of absent or reverse end-diastolic blood flow in the umbilical artery in the diagnosis of fetal distress]. AB - To examine the significance of the absence of reverse of end-diastolic (ARED) velocity in umbilical artery, outcome of pregnancy in 24 women with this complication was evaluated. Acute or chronic hypoxia was evident in 87.5% fetuses with ARED. Such situation is a definable high-risk state that demands intensive surveillance. PMID- 8001855 TI - [Evaluation of the clinical value in doing complex analysis of blood flow velocity parameters of the umbilical artery for determining prognosis of fetal status]. AB - Complex analysis of the clinical value of the doppler flow indices was undertaken. A/B, RI and PI were compared separately and in different combinations with fetal status and neonate's condition. Statistical analysis revealed that complex and detailed analysis of few quality indices is of greater clinical value and increases sensitivity, specificity and positive predictive value of the doppler technique in the sense of prognosis of fetal distress and neonate's condition. PMID- 8001856 TI - [Evaluation of blood flow in the middle cerebral artery of the fetal brain during normal pregnancy using color doppler]. AB - Transvaginal color Doppler ultrasonography was performed to analyze fetal cerebral blood flow in 62 singleton noncomplicated pregnancies. Pulsatility index and peripheral flow impedance index in middle cerebral artery were measured. Pulsatility and peripheral flow impedance indexes decrease was observed. Obtained values may be used as a reference for future investigation. PMID- 8001857 TI - [Doppler ultrasound evaluation of fetal renal arteries in normal pregnancy]. AB - Normal values of the pulsatility index in the fetal renal arteries in a group of 65 uncomplicated pregnancies were established. The measurements were obtained between 28 and 40 weeks of gestation. The values of pulsatility index may be used as a reference for further investigation of pathologic pregnancies. PMID- 8001858 TI - [Levels of thyroid hormones during pregnancy and in the perinatal period. II. Levels of iodothyronine in blood serum during cesarean section and puerperium]. AB - Analysis of T4, T3 and rT3 concentration in blood serum of 27 women during and after caesarean section was performed. Estimation of hormones using RIA was done. Changes of levels of analysed hormones differed from this found during normal delivery. Periferral conversion of T4 is discussed as a potential source of different levels of T3 and rT3. PMID- 8001859 TI - [Incidence and antibiotic resistance of coagulase-negative staphylococci in a neonatal intensive are unit]. AB - Coagulase-negative Staphylococci (CNST) are among the most common microorganisms found colonizing the skin and mucous membranes of neonates. They are also the most common cause of bacteremia in neonatal intensive care units. We analyzed the occurrence of CNST and antibiotic resistance of CNST strains. We have found 731 strains of CNST isolated from 428 intensive treated babies. Above 50% of CNST strains were resistant to: Erythromycin, Lincomycin, Tobramycin, Gentamycin, Kanamycin, Tetracyclines and Penicillins. We have observed the very high incidence of multiresistant strains. Majority of our strains were sensitive to vancomycin. However 8% of strains showed the resistance to vancomycin. PMID- 8001860 TI - [Hysteroscopic evaluation of the uterine tubal opening]. AB - The hysteroscopic evaluation of uterine openings in 23 sterile women was described. The attention was paid to morphological features of obliterated uterine openings. The hysteroscopic examination of structural changes located in uterine openings seems to be a reliable method for evaluation of potency of oviducts. This procedure may help in choosing the proper way of therapy- microsurgery or IVF. PMID- 8001861 TI - [Classical and incomplete androgen insensitivity syndromes]. AB - On the basis of investigation and observation of 41 individuals with androgen insensitivity syndrome (AIS) author confirms that at the phenotypic female and genotypic male patients the value of testosterone in plasma is 6.4 +/- 1.6 mg/ml, corresponding to that characteristic to healthy males. In the classical form there is absent or very scarce pubic hair in 100%, normal development of breasts in 97% of cases, blind vagina of mean length 5.0 +/- 2.3 cm in 97% of cases and inguinal hernia in 30% of cases. In the incomplete form of AIS normal breasts occurs in 62.5%, public hair in 50%, complete absence of vagina in 62.5%, blind vagina of mean length 2.5 cm in 37.5%, inguinal hernia in 75% and hypertrophy of clitoris of mean length 2.0 +/- 1.0 cm in 62.5%, what distinguishes this form of the syndrome from classical form. In incomplete form surgery for inguinal hernia in 87.5% is necessary. In 37.5% artificial vagina has to be created. Classical form occurs in 80.5% and incomplete form in 19.5%. The malignity of the gonads in the discussed syndrome is rare. Castration should be avoided before the patient attains full sexual maturity. Normal value at testosterone level characteristic for men suggests that the lack of sensitivity to androgens of the target cells is the main cause of the disease and is definitively caused by mutations in the androgen receptor gene. PMID- 8001862 TI - [The influence of different cryoprotectant buffers on the fertilizing ability of human sperm "in vitro". I. The choice of cryoprotective buffers and methods of freezing]. AB - We attempted to find the optimal way of cryopreservation of male gametes. We have been tested 9 cryoprotectants currently existing in the world literature. These fluids have been so far separately investigated in different centers of infertility treatment. In this study we compared the effectivity of these fluids in preservation of viable sperm. Basic seminological parameters and two variants of freezing were tested. There were noted significant differences between fast and slow cooling of sperm samples. Nevertheless after fast cooling we found a marked decrease of seminological parameters in preserved sperm when compared to fresh samples. PMID- 8001863 TI - [Comparison of continuous extradural analgesia during labor using 0.25% bupivacaine or mixtures of 0.25% bupivacaine and fentanyl]. AB - We have compared effects of epidural analgesia in labour in two groups containing 35 primiparous each and in two groups containing 35 multiparous each. We have administered either bupivacaine or bupivacaine with fentanyl. We have compared duration of the 1-st and the 2-nd stage labour, efficiency of analgesia, quantity of administered bupivacaine, method of delivery and condition of the newborn. This investigation has shown that use of 0.25% bupivacaine with fentanyl requires less quantity of bupivacaine in both groups of primiparous and multiparous. The addition of fentanyl to 0.25% bupivacaine can be beneficial alternative of epidural analgesia in labour. PMID- 8001864 TI - [The importance of DNA analysis in the diagnosis of steroid 5-alpha-reductase deficiency]. AB - The deficiency of steroid 5 alpha-reductase leads to the disturbances in sex differentiation that cause symptoms of male pseudohermaphroditism. The methods of DNA analysis used to diagnose mutations of steroid 5 alpha-reductase gene (SRD5A2) were presented and discussed. Within the group of 21 patients with the deficiency of steroid 5 alpha-reductase 2 described so far in literature, the analysis of SRD5A2 gene revealed two "major" deletions, one "minor" deletion, 16 point mutations (incl. 5 transitions and 11 transversions), in one case a mutation causing premature termination of translation and in one case mutation leading to defective splicing of the mRNA. The mutations localized in exons 2 and 5 cause a decrease in affinity of 5 alpha-reductase 2 to the substrate (testosterone), while the mutations in exons 1 and 4, a decrease in affinity to the coenzyme (NADPH). PMID- 8001865 TI - Growth hormone-binding protein in plasma is inversely correlated to placental lactogen and augmented with increasing body mass index in healthy pregnant women and women with gestational diabetes mellitus. AB - Pituitary growth hormone (GH), prolactin (PRL), placental lactogen (PL), insulin like growth factor 1 (IGF-1) and GH-binding protein (GHBP) in plasma were determined in 12 women with gestational diabetes mellitus (GDM) and in 12 healthy pregnant women during a breakfast meal tolerance test. The women with GDM showed higher prepregnancy weight, body mass index (BMI), basal levels of glucose, insulin, and C peptide compared to the pregnant controls. No difference was found between the two groups in pituitary GH, PRL, PL and IGF-1 levels. Plasma levels of GHBP were higher in the women with GDM compared to pregnant controls. In all women there was an inverse correlation between PL and pituitary GH as well as between PL and GHBP, suggesting that PL inhibits pituitary GH secretion. A positive correlation between GHBP and BMI was found in all women, and the higher BMI in the GDM women seemed to be the cause of the higher GHBP levels in this group. In all women IGF-1, an indicator of the secretory activity of lactogenic hormones as well as of nutritional state, showed a positive correlation with the birth weights of the infants and was equally indicative in both groups. PMID- 8001866 TI - Audit of uterine rupture in Maputo: a tool for assessment of obstetric care. AB - Records of 96 women who had rupture of the uterus in labor were audited to find circumstances significantly associated with pregnancy outcome. The prevalence was 1 rupture in 424 deliveries. In 74 cases (77.1%) uterine rupture occurred after hospitalization, the remaining 22 cases being emergency transfers with rupture secondary to a delivery attempt elsewhere. History of a previous cesarean section was present in 46%, whereas 54% of the women had an unscarred uterus. Maternal mortality was 7.3% whilst perinatal mortality was 62.9%. Adverse outcome for the mother was associated with ruptures occurring in unscarred uteri (p < 0.02) and outside the Maternity (p < 0.01); this latter condition also contributed to higher fetal mortality (p < 0.002). The findings confirm that delay in reaching medical care is an aggravating factor in the evolution of uterine rupture in developing countries and suggest the need for better medical attention and timely diagnosis in laboring women with unscarred uterus. PMID- 8001867 TI - Evaluation of plasminogen activators and plasminogen activator inhibitors in plasma and amniotic fluid in pregnancies complicated with intrauterine fetal growth retardation. AB - Several fibrinolytic parameters were determined in plasma and amniotic fluid from normotensive pregnancies complicated by intrauterine fetal growth retardation (IUGR) and severe preeclamptic (PE) patients with IUGR and compared with data from normal pregnancies. A significant decrease in plasminogen activator type 2 (PAI-2) and urokinase levels in plasma and amniotic fluid was observed in IUGR groups in comparison with normal pregnancy. No significant differences were observed between the control and IUGR groups in relation to the other fibrinolytic parameters, except for plasma PAI type 1 and tissue-type plasminogen activator levels, which were significantly increased in the PE group. A significant positive correlation was observed between birth weight and PAI-2 levels in both plasma and amniotic fluid, but the plasma PAI-2 levels showed a higher correlation. In conclusion, these results suggest that the PAI-2 level measured in plasma is a more adequate marker of placental function than the PAI-2 level measured in amniotic fluid. PMID- 8001868 TI - Distention of the uterus activates its multiple pacemakers and induces their coordination. AB - In the pregnant human uterus, pacemaker activities and their coordination processes were studied in labor induced by uterine distention. Electrical and mechanical activities of the uterus were simultaneously recorded in 6 midtrimester (normal, n = 4; fetal death, n = 2) and 8 term (normal, n = 7; fetal death, n = 1) patients. Initially, frequent and sporadical spike discharges which did not synchronize with low magnitude and irregular mechanical activities were noted. With time, synchronization of both activities developed. These findings were noted regardless of the gestational stage of the patient and fetal viability. The patterns of development and decreases in mechanical and electrical activities, together with their synchronization patterns, were positively and negatively controlled by uterine distention and its suspension, respectively. These results suggest that the uterus has multiple pacemakers in various locations, and uterine distention works as a trigger for the elevation of excitability and for coordinated and orthodromic activities. PMID- 8001870 TI - Changes in blood level of lipid peroxide and vitamin E during pregnancy: clinical significance and relation to the pathogenesis of EPH gestosis. AB - The present study was undertaken in order to determine the changes in blood levels of lipid peroxide and vitamin E in EPH gestosis. The mean plasma level of lipid peroxide was 0.89 +/- 0.13 nmol/ml for nonpregnant women, while for normal pregnant women it was 2.51 +/- 0.52 nmol/ml, and 4.10 +/- 0.72 nmol/ml for women with EPH gestosis. The mean plasma level of vitamin E was 6.7 +/- 1.0 micrograms/ml for nonpregnant women, while for normal pregnant women it was 14.5 +/- 2.2 micrograms/ml and 12.6 +/- 1.2 micrograms/ml for women with gestosis. The mean red cell level of vitamin E was 3.55 +/- 0.25 micrograms/ml packed red cells in nonpregnant women, while in normal pregnant women it was 2.56 +/- 0.34 micrograms/ml packed cells and 2.90 +/- 0.28 micrograms/ml packed cells for women with EPH gestosis. The mean platelet level of vitamin E was 99 +/- 25 micrograms/g protein for nonpregnant women, while in normal pregnant women it was 232 +/- 24 micrograms/ml protein and 205 +/- 32 micrograms/g protein for women with EPH gestosis. It was shown in this study that in EPH gestosis the plasma level of lipid peroxide increased while the levels of vitamin E which inhibited the formation of lipid peroxide decreased in plasma, red cells and platelets. PMID- 8001869 TI - Urinary trypsin inhibitor has a protective effect on the amnion. AB - Urinary trypsin inhibitor-related substance (UTI-R) was measured in the amniotic fluid (n = 30), first neonatal urine (n = 10), meconium (n = 10), and adult urine (n = 10). The concentration of UTI-R excreted in the neonatal urine was significantly higher than in adult urine and meconium. Positive immunostaining for UTI was observed in amnion, umbilical cord and placenta. The effect of UTI was studied on the amnion using fura-2-acetoxymethyl ester. Interleukin-1 beta (IL-1 beta) and tumor necrosis factor-beta (TNF-beta) led to a significant increase in relative fluorescence release (RFR) of fura-2 (p < 0.05 and p < 0.02, respectively) while endotoxin did not show significant changes of RFR of fura-2. The effect of IL-1 beta and TNF-beta was almost abolished after incubation of UTI with the amnion cells (p < 0.03). This suggests that UTI may have a protective effect on the amnion especially against IL-1 beta and TNF-beta. PMID- 8001871 TI - Effects of Braxton-Hicks contractions on fetal heart rate variations in normal and growth-retarded fetuses. AB - The objective of this study was to evaluate whether Braxton-Hicks contractions induce changes in fetal heart rate variation in normal and growth-retarded fetuses. 110 uncomplicated singleton pregnancies were cross-sectionally studied as well as 16 pregnancies complicated by fetal growth retardation secondary to uteroplacental insufficiency. Fetal heart rate variability was analyzed by a commercially available computerized system (2CTG Hewlett Packard, Italy) 10 min before and 10 min after the Braxton-Hicks contraction. All the included fetal heart rate tracings fulfilled the following criteria: (1) presence of a single Braxton-Hicks contraction in the 20 min considered; (2) absence of fetal heart rate decelerations after the contraction, and (3) stable fetal heart rate behavioral pattern in the period analyzed. 82 tracings of normal fetuses were analyzed during an active fetal heart rate pattern (type B) and the remaining 28 during a quiet pattern (type A). In both patterns no significant differences in delta value, long-term irregularity, short-term variability and interval index were found before and after the contraction. All the tracings of growth-retarded fetuses were analyzed during the fetal heart rate pattern A. Short-term variation and interval index significantly decreased during the first 5 min after the contraction while no significant differences were found in the other indices investigated. The decrease in these indices was significantly more marked in those fetuses developing fetal distress within 7 days. In conclusion, Braxton Hicks contractions induce a significant decrease of short-term variation and interval index only in growth-retarded fetuses. This can be useful in the early identification of fetal compromise in such fetuses. PMID- 8001872 TI - P-cadherin expression in human endometrium and endometriosis. AB - The objective of the present study was to detect the expression of P-cadherin in human endometrium and endometriosis and to compare this expression to that of E cadherin. To this end immunohistochemistry with monoclonal antibodies specific for P-cadherin and E-cadherin was applied to endometrium and endometriotic lesions obtained in the early follicular phase of the menstrual cycle from 10 patients. P-cadherin was detected in epithelial cells in all ten endometrial samples and in all glandular structures of endometriotic lesions. The staining characteristics for P-cadherin and E-cadherin were similar. P-cadherin may play a role in the maintenance of the proliferative compartment of endometrium and could have a comparable function in endometriotic lesions. PMID- 8001873 TI - Study of oestrogen and progesterone receptors in normal human endometrium during the menstrual cycle by immunocytochemical analysis. AB - Monoclonal antibodies to human oestrogen and progesterone receptors were applied to frozen sections of normal endometrium in various phases of the menstrual cycle. Both oestrogen and progesterone receptors were localised within the nuclei of target cells. There are no oestrogen or progesterone receptors in endometrial vessels. Oestrogen receptor contents remained fairly constant during the proliferative and early secretory phases but decreased markedly in the late secretory phase. This decline was more obvious in the glandular cells than in the stromal cells, where receptor staining disappeared in most cases. The receptors were localised predominantly in the glandular cells at most stages of the menstrual cycle except in the late secretory phase, where the reverse was observed. In contrast, progesterone receptors rose gradually throughout the proliferative and early secretory phases followed by a decrease to various degrees depending on the cell types in the late secretory phase. This decrease was more marked in the glandular cells where again receptor staining disappeared in most cases, whereas the receptor contents in the stromal cells only decreased to the level of the late proliferative phase. The progesterone receptors were also localised predominantly in the glandular cells at most stages in the cycle apart from the late secretory phase. PMID- 8001874 TI - Steroid sulfatase activity in human leukocytes. AB - To study steroid sulfatase activity in women in the field of obstetrics and gynecology, especially to differentiate carrier women with steroid sulfatase deficiency (recessive X-linked ichthyosis, RXLI) from normal women, steroid sulfatase activity was assayed in peripheral blood leukocytes from normal nonpregnant women, pregnant women, patients with RXLI, carriers of RXLI and in other normal males of different age. Steroid sulfatase activity in pmol/mg protein/min was significantly lower in patients with RXLI than in the other groups and significantly higher in the 3rd trimester pregnant women than in nonpregnant women and adult men. In addition, sulfatase activity was significantly higher in the 3rd trimester pregnant women than in fetuses. However, it was difficult to differentiate carrier women with RXLI from normal women because of considerable overlap between the two groups. The biochemical control mechanism of steroid sulfatase is the subject of further research. PMID- 8001875 TI - Vaginismus: an important factor in the evaluation and management of vulvar vestibulitis syndrome. AB - Dyspareunia is a common complaint in general gynecological practice. Many patients with dyspareunia suffer from vulvar vestibulitis syndrome (VVS). This syndrome constitutes severe pain on vestibular contact or attempted vaginal entry, tenderness to pressure within the vulvar vestibule and physical findings of vulvar erythema of various degrees. As a last resort, and only when all conservative treatments have failed, surgery is attempted. It has been our observation that a considerable percentage of patients with VVS present with concomitant vaginismus. Furthermore, surgery is less successful in this subgroup of patients unless the vaginismus is first treated. This report describes the evaluation and treatment of 14 patients with VVS. PMID- 8001876 TI - Risk factors in puerperal endometritis-myometritis. An incident case-referent study. AB - Postpartum endometritis-myometritis (PPEM) was identified in 51 women after vaginal delivery, who were compared with 51 healthy referent parturients, matched for age, parity and days postpartum. Socio-economic background data, past and current obstetric history and clinical data from recent delivery were analyzed. Endocervical and intracavitary cultures and blood cultures were performed and serological analyses of syphilis and HIV antibodies were carried out. No socio economic factor studied discriminated significantly between cases and referents. Previous stillbirth (OR 9.44) and previous low-birthweight delivery (OR 3.90) occurred significantly more often among cases. In recently past pregnancy preterm delivery (OR 10.07), low birthweight (OR 16.55) and serious neonatal morbidity (OR 14.27) were significantly more common among cases. Cases and referents differed also significantly in body mass index < 22.5 (OR 3.41), left mid-upper arm circumference < 25 cm (OR 2.66), haemoglobin < 100 g/l (OR 3.12) and high risk classification in antenatal care (OR 11.95). Bacterial intracavitary cultures tended to be positive and have anaerobes more frequently in cases than in referents. It is concluded that women with PPEM in the setting studied belong to a group at risk also regarding adverse fetal outcome, both in recently past and in previous pregnancies. PMID- 8001877 TI - Nonneural mediation of digital vasodilation during menopausal hot flushes. AB - Menopausal hot flushes are accompanied by profuse sweating, decreased skin resistance, modest tachycardia and cutaneous vasodilation. With the exception of the last effect, these events are consistent with an abrupt increase in sympathetic outflow. Blood flow in the human finger is controlled through sympathetic vasoconstricting nerves, and increased sympathetic activation results in digital vasoconstriction. We therefore sought to determine if digital vasodilation during hot flushes was mediated through efferent sympathetic nerves. Bilateral finger temperature and blood flow were recorded after the digital nerves on one hand had been blocked with a local injection of lidocaine. The effectiveness of the nerve blocks was verified by a reflex vasoconstriction test. Hot flushes were objectively defined using skin conductance responses recorded from the sternum. Fifteen hot flushes occurred in 8 women. Significant elevations in finger temperature and blood flow occurred during the flushes, in nerve blocked and intact fingers. These findings suggest that digital vasodilation during hot flushes is due to a circulating vasodilating substance. PMID- 8001878 TI - Visualization of blood flow in small ovarian tumor vessels by transvaginal color Doppler sonography after echo enhancement with injection of Levovist. AB - The echo-enhancing effect of an ultrasound contrast medium (Levovist) in color Doppler sonography of small vessels in ovarian tumors was studied in a group of 30 women. The vascularity of adnexal masses with a suspicion of primary carcinoma in 3 and benign lesions in 27 cases was investigated before and after injection of 300 mg/ml of Levovist. In 17 cases color flow mapping showed increased vascularity either in the cystic wall or in solid structures within the tumor. In all patients we observed enhancement of Doppler signal intensity. Our results show that Levovist facilitates waveform analysis in very small vessels with poor velocity patterns. PMID- 8001879 TI - Preoperative ultrasound assessment of omental spread in ovarian cancer. AB - The accuracy of high-resolution ultrasound in the detection of macroscopic omental metastases was evaluated in 50 consecutive patients undergoing surgery for ovarian cancer. Ultrasound provided an overall diagnostic accuracy of 83.7%, with a sensitivity of 76.6% and a specificity of 100%. The sensitivity in the diagnosis of diffuse omental involvement was 93.3%. Moreover, the overall diagnostic accuracy, sensitivity and positive predictive value of the method increased as the study progressed. In the last 25 cases examined, in fact, these values were 94.7, 90, and 90%, respectively. PMID- 8001880 TI - Variations in the number and in origin of the thyroid arteries. AB - The number of arteries providing blood supply for the thyroid gland as well as the origin of the superior thyroid and inferior thyroid arteries were examined in 132 fetuses from single pregnancies and in 144 fetuses from twin pregnancies, aging 4 to 9 months. Most frequently (81% cases) four thyroid arteries were observed. Five thyroid arteries were noted in 14.4% cases. Sources of additional thyroid arteries were described. PMID- 8001881 TI - Variability of places of origin of the human renal arteries. AB - In the material of 60 organ blocks from corpses of adults of both sexes, places of origin of the left and right renal arteries have been described in relation to each other, in relation to the place of origin of the superior mesenteric artery, to the median plane of the body, and to the aortic wall. It has been found that in 72% of the examined specimens the right renal arteries originated above the left ones, and in 56% of cases they are situated closer to the median plane of body. Distances between places of origin of the renal arteries and the origin of the superior mesenteric artery varied from 2-26 mm. PMID- 8001882 TI - Variations in quadriceps femoris muscle in human fetuses. AB - In 138 human fetuses (70 males and 68 females) aging 9 to 36 weeks variations were recorded in the shape of individual heads of quadriceps femoris muscle. The typical traits of morphology of the vastus lateralis and the vastus medialis included additional fleshy lamellae and associations with the neighbouring muscles. PMID- 8001883 TI - Relationship of corticoclaustral axon terminals to neurons of the claustrum in the cat. AB - A dark type degeneration of axon terminals was observed in the dorsocaudal part of the claustrum following lesions of the visual cortex. Most of the degenerating axon terminals had synapses mainly with dendritic spines (64.1%) and small dendrites (25.1%). Only 5.8% of degenerating axon terminals formed synaptic contacts with medium-sized dendrites, 1.0% with large dendrites and 0.5%--with other parts of the claustral neurons. 3.5% of degenerating axon terminals were observed to form a contact with more than one postsynaptic structure. Degenerating axon terminals displayed synaptic contacts exclusively of asymmetrical type with clearly identifiable postsynaptic densities which suggest corticoclaustral afferents to be excitatory. Our data strongly support the notion that there are direct synaptic contacts between the ascending arm of the corticoclaustral neuronal loop. PMID- 8001885 TI - Relation of the vestibular ganglion to the otocyst and cochlear ganglion in human embryos during 5th and 6th week of development. AB - Human embryos during developmental stages 14-17 were investigated. At stage 14 the endolymphatic appendage is already developed. The vestibulocochlear and geniculate ganglia form common ganglionic complex surrounded by mesenchymal capsule. At this stage three components may be distinguished. The differentiation of the ganglia appears in the following sequence: geniculate, vestibular, cochlear. The geniculate ganglion is rostroventral and the vestibular dorsomedial in position. PMID- 8001884 TI - Variability of the parahippocampal surface of the transverse fissure in the human brain. AB - The parahippocampal (ventral) surface of the lateral part of the transverse fissure (LTF), formed by the parahippocampal gyrus, was examined in 53 human brain hemispheres without pathological changes. Cytoarchitectonics of this region was studied on the frontal histological sections stained either with cresyl violet or with Weil method. Four types of the shape of the parahippocampal surface of LTF were distinguished. In type 1 the surface is either flat or elevated in its medial part (medial eminence; 34.0%). In type 2 the surface is elevated in its lateral part (lateral eminence, 24.5%). In type 3 there are two eminences--the lateral and the medial; both of similar height (20.8%). In type 4 the lateral eminence is distinctly higher than the medial one (20.7%). The eminences contain cytoarchitectonically different structures. The lateral eminence is formed mainly by the subiculum and CA1 area, the medial by the presubicular region. The shape of the parahippocampal surface of LTF may be of importance in assessment of the Alzheimer's disease pathology. PMID- 8001886 TI - Changes in the peripheral nerves in rats induced by vibration. AB - Effects of long-term low frequency vibrations on the structure of the sciatic and plantar nerves were examined in Wistar strain rats. Decrease in total number of nerve fibers was noted. This was associated with altered distribution of myelinated fiber diameters, disturbances in axon structure and with fiber demyelination. The extend of lesions depended upon duration of exposure and distance from the source of vibrations. PMID- 8001887 TI - [Antibody-conjugated cytostatic drugs. Uses of monoclonal antibodies for new strategies in tumor therapy]. PMID- 8001888 TI - [Strategies for minimizing homologous blood transfusion in elective interventions]. AB - The risks associated with homologous blood transfusion necessitates the development of strategies for reducing the need for it. The most effective method is certainly preoperative donation of autologous blood, which leads to an increase in the absolute numbers of erythr789789 by the time surgery is performed. Depending on the type of preparation and storage, erythrocytes may be viable for between 49 days (liquid storage) and many years (deep frozen). By employing preoperative plasmapheresis, high-quality autologous fresh frozen plasma can be made available for use during surgery. Donation of autologous blood and plasmapheresis are preoperative measures that need to be organized. Another possibility is the use of a cell separator to recycle blood lost during surgery, and may be applied intra-operatively (aspiration from the surgical wound) or postoperative (drainage). Hemodilution has but little effect in reducing homologous blood requirements. Instead of the technically complex and time consuming acute normovolemic hemodilution (ANH), the simpler hypervolemic alternative version (HHD) should be employed. Applying all the measures described above, an appreciable reduction in the need for homologous blood can be achieved. A prerequisite, however, is close cooperation between the surgeon an anaesthesiologist. PMID- 8001889 TI - [Blood transfusion in surgical gynecology. Strategies for preventing homologous blood transfusion]. AB - A statistical evaluation of homologous blood transfusions is imperative in any gynecological surgical department, to be able to define the transfusion associated risk of the individual interventions. On the basis of our own statistical data and reports in the literature, strategies for limiting the use of homologous blood are discussed. So far, experience with autologous blood transfusion in surgical gynecology is limited, and clinical studies are needed to better define its role. In special cases, the use of erythropoietin and gonadotropin-releasing hormone (GnRH) analogues extends the possibilities for reducing homologous blood transfusion. PMID- 8001890 TI - [Ambroise Pare (1510-1590). Founder of facial prosthetics]. PMID- 8001891 TI - [When should children be excused from school sports? General recommendations leave room for individual decisions]. PMID- 8001892 TI - [Recommendations for the use of measuring instruments in clinical anxiety research]. AB - The Arbeitskreis Angstforschung (AKA) brings together investigators active in the field of anxiety research and representatives of anxiety disorder outpatient clinics in German speaking countries. During its regular meetings, the decision was made to develop recommendations for the assessment of anxiety disorder patients in clinical studies. A task force of experts in pharmacological and psychotherapeutic treatments established a consensus of opinion to improve standardisation and comparability of studies originating from different centres. The AKA specifically recommends the following set of variables to be collected in all studies: (1) Demographic data: age, gender, marital status, education, employment, and living situation. (2) DIAGNOSIS: diagnoses should be obtained by clinically experienced personnel with special training in the particular assessment instruments. Structured interviews, according to the current versions of the DSM or ICD classifications are recommended. Published reliability and validity data should be available for the interviews. Examples of specific instruments meeting these criteria are given. (3) Symptoms and course: Data on the course of the disorder should cover onset, type of course, timing of episodes, currently active or in remission, as well as a complete treatment history. In addition, patient self-ratings and observer ratings should be obtained in order to allow comparisons across studies, assess the severity and measure treatment outcome. (4) Disability and restrictions in quality of life: these variables should be assessed by rating scales covering work, social and leisure activities, and family relationships. The AKA expects that these recommendations will be helpful to clinical anxiety researchers. Acceptance of common standards should improve the quality and comparability of pharmacological and psychotherapeutic studies in the complex field of anxiety disorders. PMID- 8001893 TI - [Co-enaesthetic schizophrenia. Case studies of illness perception and compliance]. AB - Against the background of clinical and anthropological considerations, the case studies of eleven patients with coenaesthetic schizophrenia (F 20.8 in ICD-10) are evaluated with regard to how the patients experience the disorders of corporal perception. Additional criteria for the evaluation are whether the disorders receive a special significance in dealing with the psychosis, and whether they influence compliance with medicinal intake. In two cases, the coenaesthesies were experienced as making the patients happy, they were used by the patients to strengthen themselves, and so the motivation for medicinal therapy was accordingly small. Of the remaining nine patients who suffered from the body perception disorder, five were not willing to accept neuroleptic therapy. The author ascribes this above all to two behaviours: the patients either deny their symptoms, or they attempt to use them to compensate for ego weakness. However, an effect of self-stabilisation through the coenaesthesies, as measured by social capabilities, is not objectively recognisable. PMID- 8001895 TI - [The dream as a tool in diagnosis, healing and life orientation in antiquity]. AB - The dream is usually discussed in connection with the work of Freud und Jung and the dreamlore initiated by these two eminent dream scientists. Therefore the dream knowledge gathered by investigators of classical antiquity is almost forgotten, although the same diagnostic and therapeutic aims have been followed by them as they are by modern psychotherapy and medicine. Hippocrates and the other Greek physicians saw in dreams indications of bodily and psychosomatic disturbances. Dreams from the gods, especially Ascelepios, helped those who travelled from afar to be healed while sleeping in the temples. Popular dream interpretation availed itself of just as sophisticated an interpretative system as has been set up by modern depth psychologists. Dreams served to give orientation in life and warn of fateful future events. In spite of its elusive quality truth is sought in dreams today as it was in antiquity. Dream interpretation was then, and is now, one of the preferential techniques of existence. PMID- 8001894 TI - [The pharmacologic and clinical profile of the new anticonvulsant felbamate--an overview]. AB - Felbamate is a new anticonvulsant which has already been marketed in some countries outside Germany, i. e., in the United States. Since marketing in Germany is in progress, one may soon expect felbamate to be in clinical use. Both the chemical structure and the probable mechanism of action are different from the currently available antiepileptic drugs. The studies already published allow to expect felbamate to improve substantially the possibilities of antiepileptic pharmacotherapy, since it is an anticonvulsant with a high efficacy in the treatment of partial epilepsy and especially with a very good tolerability. Its disadvantage are numerous interactions with other antiepileptic drugs. This article is an update review of the literature on felbamate. PMID- 8001896 TI - The implantable cardioverter/defibrillator. PMID- 8001897 TI - [The implantable cardioverter/defibrillator (ICD). Developments up to the present time and future perspectives]. AB - The implantable cardioverter/defibrillator is gaining increasing significance in the therapy of life-threatening ventricular arrhythmias. Independently, the team of Mirowski and the team of Schuder started to develop experimental automatic implantable defibrillators in the seventies. In 1980, the first human implant of an automatic defibrillator was done by Levi Watkins together with the team of Mirowski in Baltimore, USA. Since 1989 implantable cardioverter/defibrillators exhibit multiple functions among which are high energy defibrillation therapy, low energy cardioversion, antitachycardia pacing, permanent and post therapy antibradycardia pacing, diagnostic counters, and device status parameters. This offers a markedly improved technical device to the patients. Evaluation of the patient's diagnostic counters provide a detailed overview about the patient's arrhythmia history and information for optimizing antitachycardia pacing therapy and additional antiarrhythmic drug therapy. The availability of non-thoractomy transvenous lead systems and biphasic shock forms allows the insertion of the device without open chest surgery and even without subcutaneous leads resulting in low mortality rates and an exclusively transvenous system. Single-lead unipolar devices are currently investigated in clinical trials. Future development of atrial sensing lead systems may further reduce inappropriate shock therapy triggered by sinus tachycardia or atrial tachyarrhythmias, e.g. atrial fibrillation, and may be used for dual chamber stimulation. Hemodynamic sensors for determining the severity of the arrhythmia are currently under experimental evaluation. Possible prognostic indications of ICD therapy in patients without a history of malignant arrhythmias are currently studied in several prospective trials. All new directions hold promise to expand and improve the use of ICDs in patients at risk for sudden cardiac death. PMID- 8001898 TI - [The effect of the impulse form of the defibrillation shock on its effectiveness and device technology of the implantable cardiac defibrillator]. AB - Efforts have been focussed on the development of implantable cardioverter defibrillator systems that reduce the size of the devices, simplify the methods of electrode implantation, and increase device longevity. The size of implantable units is predominantly determined by the capacitors and batteries, and this is dependent on the output energy requirements. The energy required for defibrillation and therefore the size of the devices can be reduced by utilizing optimal lead systems and waveforms. This report describes our experience with various shock waveforms in 86 consecutive patients undergoing implantation of a cardioverter-defibrillator with a nonthoracotomy approach. Table 1 provides information on the demographic characteristics of the study population, the various shock waveforms and lead configurations tested. In 20 patients, a bidirectional lead configuration was tested using simultaneous and sequential monophasic waveforms. In 18 patients, simultaneous monophasic and biphasic waveforms with a fixed pulse duration of 6.3 ms were employed utilizing a bidirectional lead system. In 31 patients, a undirectional lead configuration was used, and simultaneous monophasic and biphasic shocks with a constant tilt were delivered. In 17 patients, the defibrillation efficacy of biphasic and triphasic shock waveforms with a fixed pulse duration of 10 ms was evaluated. The study design was an open, randomized and prospective evaluation in all patients. Defibrillation threshold was determined in a randomized sequence using a step down protocol. The defibrillation threshold was defined as the lowest energy required for effective defibrillation on two occasions. In the 20 patients using a bidirectional lead configuration, there was no significant difference in defibrillation energy requirements between simultaneous and sequential monophasic shock waveforms.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8001900 TI - [Indications and contraindications for therapy with implantable cardioverters/defibrillators]. AB - Despite all advances in the diagnostic and therapy of cardiovascular diseases the mortality from malignant ventricular tachyarrhythmias is still a major health problem. In addition to established therapeutic strategies in the prevention of sudden cardiac death such as antiarrhythmic drug treatment, catheter ablation or antiarrhythmic surgery the implantable cardioverter/defibrillator was introduced to clinical practice in 1980. The number of 50,000 overall implants reflects the current clinical status of the therapy with implantable cardioverters/defibrillators. Significant technical improvements in the defibrillator therapy may contribute to an increase in therapy acceptance. These advances include the introduction of nonthoracotomy lead systems, enhanced defibrillation efficacy, full programmable devices providing tiered electrical therapy, improved diagnostic Holter functions and enhanced arrhythmia detection algorithms. The major present goals of defibrillator therapy are, detection and termination of malignant ventricular tachyarrhythmias, reduction of sudden cardiac death, reduction in patient's mortality and improvement in quality of life. The efficacy and safety of defibrillator therapy to prevent sudden arrhythmic death has been proven in several large clinical investigations. The annual sudden cardiac death mortality is < 2% even in high-risk patient populations. Compared to sudden cardiac death rate there is a much higher rate of overall cardiac mortality because a defibrillator is not able to prevent nonarrhythmic cardiovascular deaths. There is a clinical impression that cardiovascular mortality is lower in patients treated with an implantable cardioverter/defibrillator compared to patients treated with other therapies. However there are no results from controlled studies providing scientific evidence that defribillator therapy can reduce overall cardiovascular mortality.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8001899 TI - [Transvenous subcutaneous implantation technique of the cardioverter/defibrillator]. AB - For years the high efficacy of implantable cardioverter-defibrillators (ICD) to prevent sudden cardiac death was impaired by the substantial perioperative mortality of the therapy. With the introduction of transvenous-subcutaneous defibrillation leads, thoracotomy could be abandoned and perioperative mortality was reduced to less than 1%. Despite frequent lead complications as dislocations, conductor fractures and isolation failures, long-term efficacy in termination of ventricular tachyarrhythmias remained approximately 98% and prevention of sudden cardiac death was not impaired. All nonthoracotomy defibrillation lead systems involve an endocardial right ventricular lead usually introduced from the left cephalic vein or directly via the subclavian vein. This lead has a pace/sense tip and at least one defibrillation electrode located in the right ventricle. Additionally, a second transvenous electrode and/or a subcutaneous patch or array electrode or the pulse generator shell has to be used for defibrillation. In combination with the biphasic defibrillation waveform, virtually all patients can be defibrillated using a combination of these electrodes. In most patients defibrillation is possible with transvenous electrodes alone and there is no need for an additional subcutaneous electrode. Smaller pulse generators have already been implanted in a subpectoral position--in many patients allowing a single incision approach as used for pacemaker implantation. Ultimately, with even smaller pulse generators ICDs should be implantable like present pacemakers in local anesthesia. This overview covers the history, models, practical aspects of implantation and testing, efficacy and complications of transvenous/subcutaneous defibrillation leads. Figures show the impact of the surgical approach on the frequency of de novo ICD implantations, X-rays of nearly all current bipolar and tripolar transvenous subcutaneous ICD lead systems, transvenous-epicardial hybrid systems and various complications. Additional figures cover lead complications not visible on X-rays. Defibrillation thresholds are compared for various lead configurations. Sensing amplitudes and pacing thresholds are compared for bipolar and pseudobipolar sense/pace leads as well as for different cardiac diseases. Tables summarize the main characteristics of current transvenous and subcutaneous ICD leads and external devices for intraoperative testing of ICD leads as well as the complications of transvenous/subcutaneous leads in three multicenter studies. PMID- 8001901 TI - [The implantable cardioverter/defibrillator]. AB - Despite all advances in the diagnosis and therapy of cardiovascular diseases, the mortality from malignant ventricular tachyarrhythmias is still a major health problem. In addition to established therapeutic strategies in the prevention of sudden cardiac death such as antiarrhythmic drug treatment, catheter ablation or antiarrhythmic drug treatment, cardioverter/defibrillator was introduced to clinical practice in 1980. The number of 50,000 overall implants reflects the current clinical status of the therapy with implantable cardioverter/defibrillators. Significant technical improvements in the defibrillator therapy may contribute to an increase in therapy acceptance. These advances include the introduction of nonthoracotomy lead systems, enhanced defibrillation efficacy, full programmable devices providing tiered electrical therapy, improved diagnostic Holter functions and enhanced arrhythmia detection algorithms. The major present goals of defibrillator therapy are detection and termination of malignant ventricular tachyarrhythmias, prevention of sudden cardiac death, reduction in patient's mortality and improvement in quality of life. The efficacy and safety of defibrillator therapy to prevent sudden arrhythmic death has been proven in several large clinical investigations In patients with this device the annual sudden cardiac death mortality is < 2% even in high-risk patient populations. Compared to sudden cardiac death rate there is a much higher rate of overall cardiac mortality because a defibrillator is not able to prevent nonarrhythmic cardiovascular deaths. There is a clinical impression that cardiovascular mortality is lower in patients treated with an implantable cardioverter/defibrillator compared to patients treated with other therapies. However, there are no results from controlled studies providing scientific evidence that defribillator therapy can decrease overall cardiovascular mortality.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8001902 TI - [Heart transplantation and sexuality. A study of 62 male patients]. AB - 119 adult male Austrian patients who had undergone heart transplantation between January 1985 and December 1990 were questioned on sexual functional disorders pre and postoperatively. Questions dealt with perceived medication effects on sexual function and libido, fear of intercourse, their worries about the sexual habits of the donor, perceived changes in sexual attractiveness and body image. They were also asked how they felt about discussing sexual matters with their doctors. 62 patients returned fully completed questionnaires. 75% of the patients were more than 45 years old (45 to 67 years). Heart transplantation had been carried out at least once longest seven years before. The patients reported a significant postoperative increase of libido accompanied by a significant decrease of physical complaints at intercourse. Problems with potency (impaired erectile rigidity) persisted, however, (Table 4, Figure 1). 23% of the patients reported that since transplantation sexuality had become a problem for them. 42% wanted to undergo treatment if available. 29% stated that sexual matters had clearly improved. 31% suspected that medication adversely affected sexual functioning, and 23% stated that in their opinion it contributed to a lowered libido. 15% felt themselves much more sexually attractive after they had undergone surgery, and 13% were considered more sexually attractive by their spouses. Only four patients reported avoiding intercourse for health reasons. One patient confirmed that he was fantasizing about the sexual habits of the unknown donor of his heart. It seems that physicians often neglect to talk about sexual matters with their heart transplant patients, though the patients consider it a very important topic (Figure 2).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8001903 TI - Multiple drug resistance, the MDR gene, and the law of maximum perversity as it applies to oncology: an hypothesis. AB - The so-called Law of Maximum Perversity, generally stated, says that when more than one outcome is possible, that which is the more adverse is the outcome most likely to occur. In medical oncology, the most obvious expression of this law is the fact that all the neoplasms that are most sensitive to cytotoxic drugs and are most curable by chemotherapy, are rare and in numerical terms are not important as causes of cancer-related deaths. Conversely, the most commonly encountered neoplasms that make up the bulk of oncologic practice and that cause over 90 per cent of cancer-related deaths, are all relatively resistant to cytotoxic agents and are virtually never curable by chemotherapy administered in standard (i.e. non-transplant) doses. It is postulated that the biological properties and the normal tissue distribution of the multidrug resistance (MDR) gene and its product p-170 glycoprotein explain the observed incidences and distribution of tumours that are sensitive or insensitive to cytotoxic agents. The normal role of MDR is to protect cells from environmental carcinogens, and the tissues that are most at risk, and most richly supplied with MDR, will produce drug-resistant neoplasms. Current attempts at MDR reversal may facilitate the treatment of some tumours that are resistant to multiple drugs but may cause severe toxic effects as a consequence of abrogating the largely unknown physiologic functions of P-170. PMID- 8001904 TI - Differential platelet-associated factor gene expression by a panel of human cell lines with megakaryoblastic properties after treatment with phorbol myristate acetate. AB - Four human megakaryocytoid cell lines, namely MOLM-1, MOLM-7, MEG-01 and HEL, were treated with phorbol 12-myristate 13-acetate (PMA) and expression of the platelet-derived growth factor (PDGF) A chain, von Willebrand factor (vWF) and endothelial cell growth factor (ECGF) genes was examined by the reverse transcriptase-polymerase chain reaction (RT-PCR) using specific primers. The gene for PDGF A chain is constitutively weakly expressed by MEG-01 cells and strong expression is induced in MEG-01, MOLM-1 and MOLM-7 but not in HEL cells after treatment with PMA for three days. All four cell lines express the vWF gene both constitutively and after exposure to PMA. None of the cell lines constitutively express the gene for ECGF but MEG-01 cells can be induced to do so after treatment with the phorbol diester. Immunohistochemical staining after exposure to PMA showed that the expression of the platelet-associated markers CD41 and CD61 was enhanced in all cell lines indicating possible differentiation along the megakaryocyte lineage. Our results illustrate differential platelet-associated factor gene expression in different megakaryoblastic cell populations in response to treatment with PMA, and suggest that expressions of the PDGF A chain gene and the ECGF gene may be good markers for megakaryocyte maturation. PMID- 8001905 TI - Primary mediastinal large cell lymphoma. AB - PURPOSE: Primary mediastinal large cell lymphoma PMLCL is a recently described entity which has provoked considerable interest lately. The unique immunophenotype of the malignant cell, as well as conflicting reports regarding its response to therapy, prompted us to review the current literature focusing on the pathological and clinical aspects of this disease. DESIGN: We reviewed the current literature that contained details on the clinical presentation, pathological profile and clinical outcome. RESULTS: Most reports agree that PMLCL typically affects a young female population and presents with symptoms related to compression of mediastinal structures. Pathologically, the malignant cells may arise from a distinctive thymic medullary B cell subpopulation which is characterized by the following phenotype: CD19+, CD21-, CD20+, CD22+. Alterations of c-myc and lack of expression of HLA class 1 antigens on the tumour cell surface have been described. Response to treatment and clinical outcome have varied from one series to another and is possibly explained by the small number of patients in most series and by the heterogeneity of therapy. In general, the outcome does not appear to be worse than that of other large cell lymphomas although, given the young age of these patients, it might be expected to be more favourable. CONCLUSIONS: Primary mediastinal large cell lymphoma is a distinct clinico-pathological entity characterized by: (1) a predominance of young adults; (2) female predominance (female/male ratio of 2:1) in contrast to the other large cell lymphomas; (3) CD19+/CD21- immunophenotype; (4) absence of HLA-class 1 antigen expression; (5) possible involvement of c-myc; (6) frequent dissemination at relapse to unusual anatomic sites in a pattern reminiscent of Burkitt's lymphoma. The role of radiotherapy and the optimal treatment for this disorder are issues that remain unresolved. PMID- 8001906 TI - Current awareness in hematological oncology. PMID- 8001907 TI - Genetic structure of the Utah Mormons: comparison of results based on RFLPs, blood groups, migration matrices, isonymy, and pedigrees. AB - The genetic structure of the Utah Mormon population is examined using 25 blood group and 47 RFLP alleles obtained from 442 subjects living in 8 geographic subdivisions. Nei's GST was 0.013 (p < 0.002) for the RFLP data and 0.012 (p > 0.4) for the blood group data, showing that only 1% of the genetic variance in this population can be attributed to subdivision effects. A comparison of intersubdivision distance matrices based on blood groups, RFLPs, migration matrices, isonymy, and pedigrees shows that genetic distances have relatively low and nonsignificant correlations with the other three types of data. However, the correlations based on RFLPs are considerably higher than those based on blood groups. Relationship matrices based on interindividual allele sharing were compared with known genealogical kinship coefficients between each pair of individuals. The correlation between the blood group and RFLP relationship matrices was small but marginally significant using the Mantel test (r = 0.014, p < 0.06). The RFLP relationship matrix correlated more highly with genealogical kinship than did the blood group relationship matrix (r = 0.023, p < 0.0001 and r = 0.012, p < 0.001, respectively). These correlations increased by approximately one order of magnitude when pairs of subjects having zero kinship coefficients were excluded. These results show that genetic distances derived from RFLPs correlate more strongly with other types of kinship than do distances based on blood groups. This probably reflects the fact that RFLPs are more neutral, have frequencies that are more accurately estimated, and contain more information about DNA sequence variation. PMID- 8001908 TI - Mismatch distributions of mtDNA reveal recent human population expansions. AB - Although many genetic studies of human evolution have tried to make distinctions between the replacement and the multiregional evolution hypotheses, current methods and data have not resolved the issue. However, new advances in nucleotide divergence theory can complement these investigations with a description of human demographic behavior during the late Middle and Upper Paleolithic (approximately the last 250,000 years). Restriction fragment length polymorphism (RFLP) and DNA sequence analyses of human mitochondrial DNAs (mtDNAs) from 25 ethnic and racial groups indicate that significant expansions occurred during the late Middle and Upper Paleolithic in 23 of the 25 populations examined. Estimates for the individual group expansion times are consistently less than 100,000 years ago with a mean expansion time of approximately 40,000 years ago. The dramatic expansions suggested by these data occurred well after modern human anatomy appeared, approximately 100,000 years ago, but are concordant with archeological evidence for the expansion of modern human technology, approximately 50,000 years ago. PMID- 8001909 TI - Distribution of the 9-bp mitochondrial DNA region V deletion among North American Indians. AB - The deletion of a 9-bp segment from the intergenic region between the mtDNA cytochrome oxidase II gene and the lysine tRNA gene has been documented mainly in individuals of East Asian ancestry and in individuals from East Asian-derived populations (e.g., Polynesia). Among Native Americans the deletion is absent among Eskimos and northern Na-Dene populations and present among most Amerind populations [sensu Greenberg (1987); i.e., all Native Americans except Eskimo Aleut and Na-Dene] that have been studied. To better characterize the frequency and distribution of the 9-bp deletion in North America, we surveyed more than 400 individuals from 59 tribes representing a variety of linguistic groups. The absence of the deletion among Eskimo and northern Na-Dene populations is confirmed. Among Amerind groups the deletion is present in all groups represented by more than six individuals. The geographic distribution of the frequencies of the deletion appears to be clinal in North America. The deletion is absent in the Artic and Subartic and reaches its highest frequency in the Southwest. This distribution is consistent with the hypothesis that the ancestors of the Amerinds and Na-Dene arrived in the New World by means of separate migrations. The presence of the 9-bp deletion in high frequencies in all the major linguistic groups in the Southwest suggests that migration among tribes was common. PMID- 8001910 TI - Optimizing utilization of DNA from rare or archival anthropological samples. AB - There is widespread interest in obtaining genetic samples from human populations worldwide for various studies of human genetic diversity. Many samples exist today only in the form of small, rare, irreplaceable, or archival samples, such as material from ancient bone, hair bulbs, or remnants of samples collected in the field decades ago for the purpose of protein and blood type analysis. Here, we describe the application of an approach to amplify DNA, which we call adapter attachment and amplification (AAA). This approach is useful for amplifying the genome in a reasonably representative way from small amounts of starting material using standard PCR-based methods. We apply a version of these methods to DNA extracted from washed red blood cells collected in the 1960s and 1970s in the Amazon basin. AAA and similar approaches may make the analysis of archival samples possible without exhausting that irreplaceable material and may lead to greatly improved efficiency in collecting and using new anthropological genetic samples. PMID- 8001911 TI - Genetic characterization of American and Western Samoans. AB - The Samoan islands were politically separated into American Samoa and Western Samoa in the early 1900s. Economic modernization is far more extensive in American Samoa. However, the Samoan archipelago has maintained a remarkable degree of sociocultural homogeneity, including intermarriage. The sociocultural exchanges presumably led to genetic homogeneity between the two Samoas. Detailed genetic comparisons and characterizations of Samoans are scanty, however. As part of a multidisciplinary study of modernization and cardiovascular risk factors in adults, we analyzed nine hypervariable nuclear DNA (HVR) and four serum protein polymorphisms in the two Samoan groups. The average heterozygosities at both DNA and serum protein loci are comparable in the two groups. As expected, the HVR loci reveal a high degree of variability (heterozygosity 30-87%) compared with the serum protein loci (heterozygosity 1-52%). A large proportion of alleles at the HVR loci, ranging from 50% to 100%, are shared between American and Western Samoa. With the exceptions of the D1S80 locus in American Samoa and the D13S118 locus in Western Samoa, the genotype distributions at all loci conform to their respective Hardy-Weinberg expectations. Sporadic occurrence of the F13B*2 allele at the F13B locus in Samoans indicates a low level of European admixture because this allele is unique to Europeans. The calculated zero values of kinship coefficients and standard genetic distances indicate minimal population differentiation between the two Samoan groups. PMID- 8001912 TI - Mountains and genes: population history of the Pyrenees. AB - The Pyrenees Mountains rise between France and Spain. At their western end live the Basques, one of the oldest populations in Europe. All the available genetic information (gene frequencies of blood groups, serum proteins, red cell enzymes, and HLA antigens) on Pyrenean populations has been gathered and subjected to two kinds of analysis: a discrete approach, in which eight separate populations have been defined according to linguistic and geographic criteria to compute genetic distances between them; and a continuous principal components analysis on gene frequencies interpolated to a regular grid. In the first approach the Pyrenean samples have also been compared to other Western European populations. Our results show that the Basque population is most genetically differentiated with respect to other Pyrenean and Western European populations. There is a strong genetic gradient along the mountain range (i.e., in an east-west direction); thus the mountains have not acted as barriers to gene flow. A Catalan-speaking sample, the Cerdanya, is slightly detached from its neighbors and seems closer to other European populations. This genetic picture together with linguistic, paleoanthropological, and archeological data points to a Mesolithic (or older) differentiation of the Cantabrian ancestors of the Basques. Moreover, the Basque genetic features are found in the northern slope of the Pyrenees far beyond the present Basque linguistic boundaries, in accordance with the most recent hypotheses on Pyrenean historical linguistics. The genetic consequences of the arrival of the first Indo-European-speaking peoples in the Iberian Peninsula are also studied; no clear genetic trace has been left of that population movement, except perhaps for the Cerdanya, an eastern valley that affords a passage between north and south. PMID- 8001913 TI - Testing hypotheses on processes of genetic and linguistic change in the Caucasus. AB - Extensive genetic diversity exists in the populations of the Caucasus. Various hypotheses on its origin and evolution were tested by comparing genetic, geographic, and linguistic distances. Seventeen polymorphic loci and 107 localities were considered, and Mantel tests of matrix association were carried out. Genetic differences correlate more with linguistic than with geographic distances; but when populations are grouped by the language spoken, this correlation loses significance, whereas genetic and geographic distances between groups appear significantly associated. Hypotheses that classify North and South Caucasian languages into distinct families or that treat all North Caucasian languages as independent linguistic entities fail to account for genetic variation better than simpler models. We interpret these results as evidence for an evolutionary process in which linguistic and genetic divergence has resulted from population subdivision and from processes of elite dominance, that is, language replacement not associated with major migratory movements. PMID- 8001914 TI - Population structure of the Chenchu and other south Indian tribal groups: relationships between genetic, anthropometric, dermatoglyphic, geographic, and linguistic distances. AB - We describe the genetic structure and interrelationships of nine south Indian tribal groups (seven from Andhra Pradesh and two from the adjoining states of Tamil Nadu and Kerala) using seven polymorphic loci (ABO, MN, RH, PGM, ACP, PGD, and LDH). R matrix analysis indicates that the Andhra Pradesh tribes are clustered and that the Kadar and Irula are genetically isolated from them. This dispersion of populations has been explained by the combination of relatively high frequencies of the alleles RH D and MN M in the Kadar and the relatively high proportions of the allele PGM*2 in the Irula. The Mahaboobnagar Chenchu subgroup is isolated from other Telugu-speaking groups because of high frequencies of the PGM*1 and ACP*A alleles. The regression of mean per locus heterozygosity (H) on distance from the gene frequency centroid (rii) reveals considerable levels of external gene flow among the Lambadi, the Yerukula, and the two Chenchu subgroups and more homogeneity in the Kolam, Koya, Yanadi, Irula, and Kadar. Mantel statistics were used to assess the relative effects of nonbiological processes (i.e., language and geography) on the morphological and genetic patterns of these subdivided populations. The significance of correlations was determined between different data sets (genetic, dermatoglyphic, anthropometric, geographic, and linguistic) at three levels involving nine, six, and five populations. Although multiple correlation analysis reveals significant combined effects of geography and language on genetics, anthropometrics, and dermatoglyphics, highly significant partial correlations suggest strong effects of geography on both anthropometry and genetics. Our analysis indicates that geographic factors have an overwhelming effect on the genetic differentiation of the south Indian tribal groups. PMID- 8001915 TI - Genetic studies on the Senegal population. II. Polymorphisms of the plasma proteins F13A, F13B, ORM1, AHSG, C6, C7, and APOC2. AB - Using isoelectric focusing and immunoblotting techniques, we tested 270 plasma samples from 3 populations of Senegal (Wolof, Peul, Tukulor) to determine genetic variation at 7 protein loci (F13A, F13B, ORM1, AHSG, C6, C7, APOC2). Four of the seven systems (F13A, ORM1, AHSG, C6) have not been studied previously in sub Saharan Africa, and one system (C7) has never been examined in any population of African ancestry. The assumption that F13B*6, F13B*23, and APOC2*2 represent African marker alleles is supported by this study. At the AHSG locus we observed a four-allele polymorphism rather than the two-allele polymorphism commonly seen in other ethnic groups. At the C6 locus, in addition to the two common alleles C6*A and C6*B, we observed three other alleles, one of which (C6*A3), found at polymorphic frequencies, seems to be another example of a unique African allele. The C7 locus was found to be monomorphic in the Peul but polymorphic in the Wolof and the Tukulor. At the F13A and ORM1 loci, Senegalese have allele frequencies similar to those reported for American blacks. All three Senegalese samples display typical African features, such as a high frequency of the F13B*2 allele and the presence of the APOC2*2 allele at a polymorphic level. However, some differences in allele frequencies have been found between the three groups, and this could have implications for reconstructing their remote history.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8001916 TI - Isolation factors and kinship by isonymy in a group of parishes in northern Tuscany (Italy): influence of within-parish similarity level on between-parish similarity pattern. AB - We investigate the influence of within-parish similarity level on between-parish similarity pattern in surname analysis through a study of the relative roles of various isolation factors accounting for the population structure within a municipality (21 parishes) in the hilly part of northern Tuscany. One surname per family was collected (N = 3052), and the pattern of kinship observed by isonymy was compared with the expected patterns based on demogeographic variables. The fit of the isolation by distance model is substantially improved with the inclusion of values at zero geographic distance (i = j). Differentiation in migration rate was clearly shown by the local kinship values, which are highly correlated with the demogeographic features of the parishes under study. Furthermore, the strong heterogeneity of the local kinship values seems to be the major factor responsible for the poor relation of the off-diagonal values of the kinship matrix to the expected isolation pattern. In fact, the kinship matrix weighted on the basis of the local kinship values points to a pattern of similarity among parishes congruent with the demogeographic structure of the population. On the whole, the results indicate that at the low hierarchical level of parishes the extreme localization of surnames is a disturbing factor in population structure analysis. A simple method to overcome this problem has been proposed. PMID- 8001917 TI - Health of populations in northern Queensland aboriginal communities: change and continuity. AB - We show that Australian Aborigines living in North Queensland have had an impressive decline in infant mortality over the past 50 years. Since the early 1970s, much of the decline can be attributed to preventive and curative medical services. On the other hand, the growth trajectory of infants and children has improved only slightly since the early 1970s, and mean and median weights are still well below international standards. In addition, there is no evidence that life expectancy at birth has improved significantly since the early 1970s. The pattern of declining infant mortality and stagnant life expectancy is accounted for by unchanging mortality at older ages. The major contributing causes are heart disease and accidents and violence. We suggest that the decline of infant mortality is the result of specific policy decisions made by the providers of preventive health services that infant health would be the focus of their efforts. The result was that many other aspects of health were not dealt with and adult mortality stagnated. We also suggest tentatively that the reduction in infant mortality coupled with persistent high rates of low birth weight and low weight for age at 1 year may be related to the high rates of young adult deaths from ischemic heart disease observed in Aboriginal populations. PMID- 8001918 TI - The utility of the polymerase chain reaction as a screening method for the detection of antigen receptor gene rearrangements. PMID- 8001919 TI - The neu-oncogene: more than a prognostic indicator? AB - Overexpression of the neu-protein, evidenced as membrane staining by immunohistochemistry, is detected in approximately 20% of invasive duct cell carcinomas, in approximately 50% of in situ duct cell carcinomas, and in almost 100% of cases of Paget's disease. Apart from a growth stimulatory effect, the molecule plays an important role in cell motility of tumor cells by the activity of a motility factor, which acts as a specific ligand for the neu-protein. The motility factor induces chemotaxis of neu-overexpressing breast cancer cells. The motility function of the neu-protein may lead to an increased metastatic potential of neu-overexpressing breast tumors. Also in Paget's disease of the breast, a motility factor secreted by epidermal keratinocytes attracts the neu overexpressing Paget's cells by chemotaxis and leads to invasion of the epidermis by the tumor cells. PMID- 8001920 TI - Optimal primer selection for clonality assessment by polymerase chain reaction analysis: I. Low grade B-cell lymphoproliferative disorders of nonfollicular center cell type. AB - Recent polymerase chain reaction (PCR)-based studies focused on the detection of immunoglobulin heavy chain gene (IgH) rearrangements have suggested that clonal populations may be amplified more easily from certain categories of B-cell neoplasia than others and that primer makeup can be a critical factor in successful amplification. However, these particular reports contained relatively few low grade B-cell lymphoproliferative disorders of nonfollicular center cell type (LG-BLPD) and used only a limited panel of available primer sets for PCR amplification of monoclonal B-cell populations. To address this issue more extensively we evaluated 156 samples of LG-BLPD by the PCR to determine optimal primer selection in this setting. All cases were classified according to standard morphological and immunophenotypic criteria, with monoclonality documented by Ig light chain restriction analysis. The LG-BLPD included 33 cases of chronic lymphocytic leukemia (CLL), 57 cases of small lymphocytic lymphoma (SLL), 10 cases of atypical CLL, 32 cases of mantle cell lymphoma (MCL), 17 plasma cell neoplasms (PCNs), and seven cases of hairy cell leukemia (HCL). All primer sets included a 3' IgH joining region consensus primer, whereas the 5' IgH variable region (VH) primer was different in each set. The first-line panel included the following: Set 1, VH-framework III consensus primer, and Set 2, seven separate VH framework I family-specific primers. A reserve panel of alternate VH consensus primers directed at framework II or III regions was used only when Set 1 showed no evidence of B-cell monoclonality.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8001921 TI - Optimal primer selection for clonality assessment by polymerase chain reaction analysis: II. Follicular lymphomas. AB - Prior studies have shown variable success in amplification of monoclonal B-cell populations from follicular lymphomas (FLs) of germinal center cell origin using the polymerase chain reaction (PCR). We examined 60 FLs by the PCR to determine optimal primer selection for detection of clonal immunoglobulin heavy chain gene (IgH) rearrangements in this common group of B-cell lymphomas. Each primer set included a 3' IgH joining region consensus primer; the 5' primer was different in each reaction. The first-line panel included the following: Set 1, bcl-2 major breakpoint region (mbr) primer; Set 2, bcl-2 minor cluster region (mcr) primer; Set 3, IgH variable region framework III consensus primer; and Set 4, seven separate IgH variable region framework I family-specific primers. A reserve panel also was used. The efficiency of monoclonal B-cell population amplification differed among primer sets. The bcl-2-targeted primer pairs (Sets 1 and 2) were most efficient and amplified 42 (70%) of 60 cases. Of these, the mbr and mcr primer sets detected monoclonality in 38 and four cases, respectively. Set 3 amplified monoclonal B-cell in 38 and four cases, respectively. Set 3 amplified monoclonal B-cell populations in 31 (52%) cases and Set 4 detected similar populations in only 27 (45%) samples. When results from primer Sets 1, 2, and 3 were combined, 49 of 60 (82%) FLs showed evidence of B-cell monoclonality by the PCR. Three of the 11 negative cases were documented as monoclonal with primer Set 4, and three additional samples were amplified only with our reserve panel.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8001922 TI - Ultrastructural cytochemical demonstration of proteoglycans and calcium in the extracellular matrix of chondroblastomas. AB - To clarify the characteristics of the extracellular matrix of chondroblastomas, six cases were studied under the electron microscope, with special reference to proteoglycans and calcium in the cellular areas. In ruthenium hexammine trichloride (RHT)-stained sections the matrix was observed to be composed of rounded or polygonal fine granules and unbanded thin filaments that appeared to link neighboring granules together. Treatment with potassium-pyroantimonate showed intracellular accumulation of precipitates, mainly localized within the cisternae of the rough endoplasmic reticulum as well as in the extracellular matrix. The presence of calcium in the precipitates was confirmed using x-ray energy dispersive analysis. These findings, similar to characteristic features observed in calcifying systems, support the theory that chondroblastomas are of chondrogenic origin. PMID- 8001924 TI - Detection of human papillomavirus in laryngeal lesions by in situ hybridization. AB - Human papillomavirus (HPV) is associated with human neoplasms of squamous epithelium. Squamous papillomas and verrucous carcinomas are two types of squamous neoplasms of the larynx that present difficult problems in differential diagnosis. Using in situ hybridization with biotinylated DNA probes, we examined benign squamous papillomas and verrucous squamous carcinomas of the larynx for the presence of HPV. Forty-two biopsy specimens from 18 patients with laryngeal papillomas and 11 biopsy specimens from seven patients with verrucous carcinomas were obtained from the files of Pennsylvania Hospital, Philadelphia, PA. Tissue sections were hybridized with an HPV DNA cocktail. The HPV-positive cases then were subtyped further with DNA probes specific for HPV subtypes 6/11, 16/18, and 31/33/35. All benign squamous papillomas (42 of 42) were positive for HPV subtype 6/11. None of the verrucous carcinomas contained demonstrable HPV (none of 11). Some of the squamous papillomas were recurrences, which shows the persistence of the virus. These results indicate that laryngeal papillomas may be related to HPV, but verrucous carcinomas are not. PMID- 8001923 TI - The placental site nodule: an immunohistochemical study. AB - The placental site nodule and plaque (PSN-P) is a recently described, benign proliferation of intermediate trophoblast cells (ITs) in the endometrium or endocervix occurring after an intrauterine gestation. We performed an extensive immunohistochemical study of 11 cases of PSN-P. Cytokeratins (AE1/AE3 and MAK 6) were strongly positive in all cases stained. Epithelial membrane antigen (EMA) was positive in all cases, in 5% to 75% of lesional cells. Expression of human placental lactogen (hPL) was weak and focal, and a minority of cases were positive for human chorionic gonadotropin (hCG). More helpful in identifying the trophoblastic nature of the lesion was pregnancy-specific beta-1 glycoprotein (SP1), which was present in 100% of cases, and placental alkaline phosphatase (PLAP), present at least focally in 90% of cases stained. Vimentin was strongly positive in all cases stained. The presence of vimentin, SP1 and PLAP in PSN-P has not been documented previously. In our opinion cytokeratin, vimentin, and SP 1 are the most important monoclonal antibodies to aid in the differential diagnosis of PSN-P. PMID- 8001925 TI - DNA aneuploidy in prostatic adenocarcinoma: a frequent event as shown by fluorescence in situ DNA hybridization. AB - Fluorescence in situ hybridization (FISH) using specific DNA probes for chromosomes 1, 7, 10, and Y was performed on 53 prostatic tissue samples obtained from 33 radical prostatectomy specimens and two benign control specimens. The 53 samples from carcinomatous prostates included 33 cancerous and 20 noncancerous samples. Additionally, four metastatic lymph node specimens were examined. Clonal chromosome abnormalities were observed in 78% of the tumors studied. They were detected in a higher proportion in stage pT2 and pT3 tumors (86% and 88%, respectively) compared with stage pT1 tumors (25%). No stage pT4 tumor was analyzed. There was evidence of remarkable focal intratumoral heterogeneity documented by the study of two samples from the same tumor in three of six cases. Comparing FISH determined ploidy patterns with DNA flow cytometry (FCM) in 22 samples, FISH showed aneuploidy whereas FCM showed none. PMID- 8001926 TI - Epstein-Barr virus-associated primary malignant lymphomas of the pleural cavity occurring in longstanding pleural chronic inflammation. AB - Primary pleural non-Hodgkin's lymphomas (NHLs) have been described mostly in Japan and occasionally in western countries. We report three cases occurring in nonimmunocompromised patients demonstrating close similarities to the Japanese cases. These lymphomas occurred more than 20 years after thoracoplasty for the treatment of pleural or pulmonary tuberculosis. They were all high grade lymphomas of B phenotype (two immunoblastic with plasmocytoid differentiation and one immunoblastic with anaplastic large cells). In situ hybridization (ISH) detected small nuclear RNAs encoded by Epstein-Barr virus (EBERs) in most lymphomatous cells in all cases. This suggests a link between primary pleural lymphoma and the longstanding chronic inflammation, which could favor a clonal evolution of Epstein-Barr virus (EBV)-infected B cells through the production of growth factors or immunosuppressive cytokines produced by inflammatory cells. PMID- 8001927 TI - Tumor necrosis factor-alpha mRNA and protein in endometrial tumors: analysis by in situ hybridization and immunocytochemistry. AB - Abnormal expression of polypeptide growth factors and their receptors is closely associated with tumorigenic transformation. In this study tumor necrosis factor alpha (TNF-alpha) mRNA and protein were analyzed in polyps and proliferative lesions of endometrium as well as in low and high grade endometrial tumors by using in situ hybridization and immunocytochemistry. All samples contained products of the TNF-alpha gene. Histochemical scores (HS), which reflect the proportion of cells positive for TNF-alpha message or protein and the intensities of the signals, were higher for epithelial than for stromal cells. Benign lesions (endometrial polyps) contained little TNF-alpha mRNA or protein, whereas specific message was abundant in proliferative lesions (hyperplasia, adenofibroma). Although neoplastic cells in both low and high grade endometrial tumors contained TNF-alpha mRNA, two major differences were observed: HS for TNF-alpha mRNA were significantly less in low grade than in high grade neoplasms, and TNF-alpha message was restricted to the nucleus in low grade adenocarcinoma cells but was abundant in the cytoplasm of high grade tumor cells. In contrast to cells in benign and proliferative lesions, TNF-alpha protein scores in endometrial tumor cells were inversely rather than positively correlated with TNF-alpha mRNA scores. Collectively, the findings in this study are consistent with the postulate that TNF-alpha is useful to endometrial tumor cells and suggest that production may increase as cells diverge from normal. PMID- 8001928 TI - A population-based autopsy study of sudden, unexpected deaths from natural causes among persons 5 to 39 years old during a 12-year period. AB - All unexpected deaths in New Mexico from 1977 to 1988 were reviewed. By statute each such death must be reported to the Office of the Medical Examiner (OMI) and according to institutional policy autopsied even when death is presumed to be from natural causes. From this group the 650 index cases that form the basis of this report were obtained. The crude rate of sudden, unexpected death among New Mexico residents 5 to 39 years old during the study period was 6.6/100,000 persons at risk. As documented by autopsy, the underlying cause of death in a majority of these cases (53.4%) was related to cardiovascular disease and alcoholism. Male persons in general are at increased risk for sudden, unexpected death, and American Indian and black male persons are at greater risk than their Anglo and Hispanic counterparts. American Indians account for a disproportionate share of the unexpected deaths resulting from alcoholism, and black male persons are at particular risk for unexpected death resulting from cardiovascular diseases. This report emphasizes the importance of life style and diet in the well-being of persons 5 to 39 years old. PMID- 8001929 TI - p53 and proliferating cell nuclear antigen expression in JC virus-infected cells of progressive multifocal leukoencephalopathy. AB - Progressive multifocal leukoencephalopathy (PML), a demyelinating disease of the central nervous system (CNS) caused by infection with JC papova virus (JCV), is characterized by marked atypical changes in the glial cells. The JCV T protein binds cellular p53 (a tumor suppressor gene product), which as a result loses its normal down regulating influence on the cell cycle. We hypothesized that this binding would stabilize p53 and prolong its half life, leading to its immunohistochemical detection. To prove our theory combined JCV DNA:DNA in situ hybridization (ISH) and glial fibrillary acidic protein (GFAP) immunohistochemistry (IHC) as well as p53/GFAP double IHC were performed on routinely processed sections of five brains obtained at autopsy and two cerebral biopsy specimens from seven patients with PML. All specimens showed JCV infected oligodendrocytes and bizarre looking astrocytes that immunostained strongly for p53. In addition, because loss of p53 function results in proliferating cell nuclear antigen (PCNA) overexpression PCNA/GFAP double IHC was carried out, and a positive immunoreaction was obtained in JCV infected cells in the two biopsy specimens. The evidence of p53 immunoreactivity in JCV harboring glial cells seems to indicate a link between the JCV induced stabilization/inactivation of p53 and the striking tumorlike glial changes seen in PML. Proliferating cell nuclear antigen overexpression in these cells further supports this pathogenetic construct. PMID- 8001930 TI - p53 but not erbB-2 expression is associated with rapid tumor proliferation in urinary bladder cancer. AB - Tumor proliferation in bladder cancer is associated with tumor behavior. To assess the association between Ki-67 labeling index (LI), p53, and c-erbB-2 overexpression, formalin-fixed tissue samples of 160 patients with transitional cell carcinoma (TCC) of the urinary bladder were studied by immunohistochemistry. Ki-67 LI was strongly associated with tumor stage (P < .0001), tumor grade (P < .0001), and p53 status (P = .0014) but not with erbB-2 overexpression (P > .2). Ki-67 LI was higher in p53-positive tumors (19%) than in p53-negative tumors (14%) when all stages were compared. Ki-67 LI was independent of p53 expression in pTa tumors (p53-positive, 9%; p53-negative, 11%), showing that p53 overexpression alone is not sufficient to induce rapid tumor cell proliferation in pTa tumors. Ki-67 LI also was independent of p53 expression in pT2 to pT4 tumors (p53-positive, 20%; p53-negative, 23%), indicating that p53 expression is not necessary for rapid tumor cell proliferation in advanced stages. However, there was a striking difference in Ki-67 LI between p53-positive pT1 tumors (22.0% +/- 8.8 standard deviation [SD]; n = 20) and p53-negative pT1 tumors (9.7 +/- 8.3 SD; n = 22; P = .0001). These results suggest that increased proliferation in p53-positive pT1 tumors is caused by additional alterations that occur during tumor progression. PMID- 8001931 TI - Composite cytological smears of pelvic lymph nodes at the time of radical prostatectomy to identify nodal metastases. AB - Many urologists will abort a radical prostatectomy (RP) after intraoperative identification of regional lymph node (LN) metastases because RP in these patients is not curative. Because frozen section techniques are time consuming and incompletely sample LNs, we evaluated the efficacy of performing a composite cytological smear (CCS) by sampling all grossly identifiable LNs. Two hundred and fifty RPs performed from November 1991 to June 1992 yielded on permanent section 33 (+) pelvic lymph node dissections (PLNDs) (6.6%) in 25 RPs (10%). Eleven (33%) of the 33 PLNDs with metastases were grossly suspicious, all were identified by CCS (median percentage of positive LNs per PLND = 33; median size of the largest metastasis = 11 mm). Of the remaining 22 grossly negative PLNDs with tumor, only seven (32%) were detected by CCS (median percentage of positive LNs per PLND = 13; median size of largest metastasis = 3 mm). In the 15 cases missed by CCS the median percentage of positive LNs per PLND was 14, and the median size of the largest metastasis was 1 mm. This method reliably detected LN metastases measuring more than 2 mm as long as the positive LN was grossly recognizable as an LN and thus sampled by CCS. In conclusion, CCS is highly specific but insensitive for the detection of limited numbers of micrometastases, which are the most common type of metastases in patients with low clinical stage disease. A combined technique employing frozen sections on smaller nodes and CCS on larger nodes may be more effective in identifying small metastatic deposits. PMID- 8001932 TI - CD26/dipeptidyl peptidase IV expression in human lymphomas is restricted to CD30 positive anaplastic large cell and a subset of T-cell non-Hodgkin's lymphomas. AB - CD26 is identical to the cell surface ectoenzyme dipeptidyl peptidase IV (DPPIV). CD26/DPPIV is associated with T-cell activation and proliferation and also may function as an auxiliary adhesion factor. Although CD26/DPPIV has been previously studied on lymphoid populations and on leukemias/lymphomas of B- and T-cell phenotype, little is known about its expression and functional role in some specific types of lymphomas, such as CD30-positive anaplastic large cell (ALC) lymphomas and Hodgkin's disease (HD). A series of 81 lymphoma samples, including 23 cases of HD, 17 cases of CD30-positive ALC lymphomas, 41 cases of other non Hodgkin's lymphomas (NHL), and a panel of HD- or ALC lymphoma-derived human cell lines were evaluated for CD26/DPPIV expression by enzyme histochemistry and immunohistochemistry on frozen sections and cell smears. CD26/DPPIV protein was expressed on neoplastic cells in 12 of 17 (71%) ALC lymphomas irrespective of their antigenic phenotype and in seven of 15 (47%) T-cell NHLs. In contrast, we did not detect CD26/DPPIV expression in tumor cells from 26 cases of B-cell NHL other than ALC lymphomas or in Reed Sternberg (RS) cells and variants of 21 of 23 HD cases. Accordingly, CD26/DPPIV expression was maintained on the CD30-positive ALC lymphoma cell line Karpas 299, but the molecule was not detected on HD derived cell lines of B, T, or non-B non-T phenotype. These results may support a new potential tool for the phenotypic separation of ALC lymphomas from HD based on the differential expression of the CD26/DPPIV molecule. Moreover, given the demonstration that CD26/DPPIV is identical to the human adenosine deaminase (ADA) binding protein, it could be speculated that CD26/DPPIV also may function by interacting with ADA to regulate the growth of CD26/DPPIV expressing neoplastic cells in ALC lymphomas. PMID- 8001933 TI - Intraepidermal squamous carcinoma (Bowen's disease) of the nipple. AB - A case of Bowen's disease of the nipple clinically resembling Paget's disease is reported. This lesion was differentiated from other pagetoid lesions by negative histochemical stains for mucin and melanin, positive immunohistochemical preparation for high-molecular weight cytokeratin 66 kd (904) using adequate controls, and electron microscopic findings of squamous cell features. The therapeutic implications of such a pagetoid nipple lesion in the absence of an underlying breast carcinoma are discussed. PMID- 8001934 TI - Induction of proliferating cell nuclear antigen in cervical human papilloma virus lesions. PMID- 8001935 TI - Myocarditis or rejection in a transplant heart. PMID- 8001936 TI - Undergraduate teaching in genitourinary medicine. PMID- 8001937 TI - Expanded gold standard in the diagnosis of Chlamydia trachomatis in a low prevalence population: diagnostic efficacy of tissue culture, direct immunofluorescence, enzyme immunoassay, PCR and serology. AB - OBJECTIVE: To evaluate the diagnostic efficacy of chlamydia culture, direct immunofluorescence (DFA), direct enzyme immunoassay (EIA), polymerase chain reaction (PCR) and serology by defining positive culture or at least two positive non-culture tests as true positive. SETTING: Three gynaecological departments located in separate areas of Sweden. PATIENTS AND DESIGN: All pregnant women requesting abortion during a six month period were included. In cases with unconfirmed non-culture tests, reculture with multiple passage and PCR on the culture transport medium was performed for confirmation. Serum was analysed for chlamydial antibodies type IgG, IgM and IgA using microimmunofluorescence. RESULTS: 18 of 419 (4.3%) patients were positive for chlamydia according to the defined criteria. Twelve of 419 (2.9%) were positive in standard culture (primary inoculation). The sensitivity of standard culture, DFA, EIA and PCR were 66.7%, 77.8%, 64.7% and 71.4% respectively. The specificity 100% (by definition), 99.5%, 100%, 100% respectively. The positive predictive value 100% (by definition), 87.5%, 100%, 100% respectively. Negative predictive value 98.5%, 99.0%, 98.5%, 98.9% respectively. Serum IgG titre of > or = 64 and > or = 1024 gave positive predictive values of 10% and 21% respectively. CONCLUSIONS: When an expanded gold standard is used, the specificity and positive predictive value of the non culture tests used are comparable with that of standard culture even in this low prevalence population. Standard culture underestimated the chlamydia prevalence by 33%. The prevalence found represents a decrease from 10 to 2.9% of culture verified chlamydia during four years in comparable populations. Chlamydial antibodies of certain immunological classes are not necessarily present in cases with chlamydia. PMID- 8001938 TI - Chlamydia trachomatis-specific antibodies in patients with pelvic inflammatory disease: comparison with isolation in tissue culture or detection with polymerase chain reaction. AB - OBJECTIVE: The detection of acute phase antibodies against C trachomatis and its comparison with tissue culture or polymerase chain reaction (PCR) on samples of cervix and urethra obtained from patients with pelvic inflammatory disease (PID). METHODS: In the academic hospital Dijkzigt, Rotterdam, The Netherlands, prospective investigations were performed on 49 consecutive patients who were admitted with the diagnosis of PID. Infections with C trachomatis were traced using tissue culture, PCR or by determining acute phase IgG and IgM antibodies. Differences between the sensitivities of serology and tissue culture or PCR were calculated using the Fisher exact test. RESULTS: C trachomatis infection was detected more often in PID patients using serology in comparison with PCR (p < 0.05) or tissue culture (p < 0.05). All patients who were positive in tissue culture also had acute phase antibodies. CONCLUSION: The establishing of acute C trachomatis infections in PID patients on the basis of serology was superior to either tissue culture or PCR on samples obtained from cervix and urethra. PMID- 8001939 TI - Zinc levels of serum and cervicovaginal secretion in recurrent vulvovaginal candidiasis. AB - OBJECTIVE: To determine whether zinc deficiency in serum or vulvovaginal secretion is a risk factor for recurrent vulvovaginal candidiasis. DESIGN: Prospective and controlled study. SETTING: Department of Dermatology, University of Vienna. SUBJECTS: 21 women who had experienced at least three documented episodes of acute vulvovaginal candidiasis within the previous 12 months. Fifteen women without anamnesis of vulvovaginal candidiasis as a control group. INTERVENTIONS: Blood samples were drawn for measurement of plasma zinc levels. Lavage of the vagina and ectocervix was performed with sterile saline solution for measurement of cervicovaginal zinc levels. MAIN OUTCOME MEASURES: Zinc levels of serum and cervicovaginal secretions were determined by flame atomic absorption spectrophotometry. RESULTS: We found no significant difference in the mean zinc concentration of plasma and cervicovaginal secretions between the recurrent vulvovaginal candidiasis and the control group. (p value for serum = 0.71, p value for secretion = 0.80). Zinc levels of plasma and cervicovaginal secretions showed no correlation (patient group: r = -0.05, control group: r = -0.07). CONCLUSION: It is well known that zinc not only exerts a major impact on different immune functions, but also participates in growth and morphogenesis of Candida albicans. Our results could not confirm the previous hypothesis that zinc deficiency of serum is a risk factor in recurrent vulvovaginal candidiasis. It is possible that the local zinc level of cervicovaginal secretions essentially influences antifungal activity of third generation azole antimycotics. PMID- 8001940 TI - Survey of undergraduate teaching in genitourinary medicine in Britain. AB - OBJECTIVE: To determine whether the time allocated for undergraduate teaching of genitourinary medicine has changed since 1984 and to determine the impact of HIV/AIDS on the teaching of the specialty. METHODS: A self completion questionnaire was sent to the consultant in charge of each department of genitourinary medicine attached to a UK medical school. RESULTS: Replies were received from all twenty seven medical schools. Most schools (24/27) offer a course of lectures accompanied by clinical teaching; however, one medical school does not include teaching of genitourinary medicine in the undergraduate curriculum at all and two others are unable to offer all students clinical tuition. The mean time devoted to lectures is 6.7 hours (range 0-15 hours) made up of 4.8 hours of genitourinary medicine lectures and 1.9 hours of lectures on HIV/AIDS. The mean time allocated for clinic-based teaching of each student is 9.2 hours (range 0-27 hours). On average the time allocated for lecturing and clinical teaching of the speciality has decreased since 1984 although there is considerable variation between schools (time for clinical teaching and lecturing combined ranges from 0-41.0 hours). CONCLUSIONS: The findings of this survey suggest there is considerable variation in both the quantity and quality of undergraduate teaching of genitourinary medicine provided throughout the UK. PMID- 8001941 TI - Feigned HIV infection/AIDS: malingering and Munchausen's syndrome. AB - Feigned HIV infection or acquired immunodeficiency syndrome (AIDS), in which people mimic infection with or disease due to HIV, accounted for 1.7% of admissions to our specialist HIV unit in Central London over a 5 year period. Of 12 patients with feigned HIV/AIDS, 11 were HIV antibody-negative, and one refused testing. Presenting histories were sometimes grandiose, unusually tragic, or unlikely in relation to the patients' healthy appearance, and often included admissions to other specialist HIV units. Substance abuse was suspected in over half of the patients described, a higher frequency than that observed in our HIV infected patient population. The possibility of feigned HIV/AIDS should be remembered in persons with self-reported HIV infection. Recognition of this condition is important to avoid costly and potentially dangerous investigation and therapy. PMID- 8001942 TI - Male circumcision and common sexually transmissible diseases in a developed nation setting. AB - OBJECTIVE: To determine whether the circumcision status of men affected their likelihood of acquiring sexually transmissible diseases (STDs). DESIGN: A cross sectional study employing an anonymous questionnaire, clinical examination and type specific serology for herpes simplex virus type 2 (HSV-2). SETTING: A public STD clinic in Sydney, Australia. SUBJECTS: 300 consecutive heterosexual male patients. MAIN OUTCOME MEASURES: Associations between circumcision status and past or present diagnoses of STDs including HSV-2 serology and clinical pattern of genital herpes. RESULTS: 185 (62%) of the men were circumcised and they reported similar ages, education levels and lifetime partner numbers as men who were uncircumcised. There were no significant associations between the presence or absence of the male prepuce and the number diagnosed with genital herpes, genital warts and non-gonococcal urethritis. Men who were uncircumcised were no more likely to be seropositive for HSV-2 and reported symptomatic genital herpes outbreaks of the same frequency and severity as men who were circumcised. Gonorrhoea, syphilis and acute hepatitis B were reported too infrequently to reliably exclude any association with circumcision status. Human immunodeficiency virus infection (rare among heterosexual men in the clinic) was an exclusion criterion. CONCLUSIONS: From the findings of this study, circumcision of men has no significant effect on the incidence of common STDs in this developed nation setting. However, these findings may not necessarily extend to other setting where hygiene is poorer and the spectrum of common STDs is different. PMID- 8001943 TI - Risk factors for hepatitis C virus infection among injecting drug users in Sydney. AB - OBJECTIVE: To study risk factors for hepatitis C virus (HCV) infection in injecting drug users (IDUs) from central Sydney. SETTING AND SUBJECTS: All IDUs attending a primary health care facility in central Sydney between December 1991 and November 1992 who underwent HCV antibody testing. METHODS: Information was obtained retrospectively from client forms routinely completed at the time of medical consultation. Additional information on injecting history and practice was obtained from the registration forms of subjects who also attended the needle syringe exchange programme at the same health care facility. RESULTS: Of the 201 IDUs tested, 118 (59%) had HCV antibodies, which did not differ significantly between males and females. HCV prevalence increased significantly with age, being highest in IDUs who were aged 35 years or more (93%) and lowest in IDUs aged under 20 years (17%). HCV prevalence increased significantly with time since first injecting, from 26% for IDUs who had injected for less than 3 years to 94% for those who had injected for more than 10 years. HCV prevalence was also significantly higher in heterosexual IDUs as compared with homosexual male IDUs, and in opiate users as compared with stimulant users, even after adjustment for age and duration of injecting. HCV prevalence was strongly associated with exposure to hepatitis B virus, but was not associated with exposure to HIV. CONCLUSION: Recent HCV transmission indicates ongoing injecting risk behaviour despite HIV prevention efforts, and underlies the potential for increased transmission of HIV through the sharing of injecting equipment. Within the population of IDUs, those who are heterosexual or inject heroin appear to be at increased risk of HCV infection. PMID- 8001944 TI - Hepatitis A seroprevalence in homosexual and heterosexual men. AB - OBJECTIVE: To determine the seroprevalence of hepatitis A antibodies in homosexual and heterosexual males attending a genitourinary medicine (GUM) clinic. DESIGN: Prospective study of male patients recruited from a GUM clinic during a 10 week period in 1993. SETTING: Central London outpatient GUM department at Chelsea and Westminster Hospital. SUBJECTS: 255 patients were recruited, comprising 185 homosexual and 70 heterosexual males. Ninety two men were known to be HIV-positive, of whom 89 were homosexual. MAIN OUTCOME MEASURES: Serum samples were screened for both IgM and IgG antibodies to hepatitis A by enzyme linked immunoassay. Results were matched to an anonymously completed questionnaire. RESULTS: 81 of the 255 subjects (31.8%) had been exposed to hepatitis A, two of whom were IgM positive. There were similar hepatitis A seroprevalence rates in homosexual (32.4%) and heterosexual men (30.0%). Although 48.1% of the homosexual men were known to be HIV-positive, compared with 4.3% of the heterosexuals. Hepatitis A seroprevalence remained comparable in both groups after patients with known HIV infection were excluded from the analysis. 11.4% of the heterosexual men admitted to oral-anal sexual contact compared with 62.2% of the homosexual men. This sexual practice was not associated with antibodies or a past history of hepatitis A exposure. CONCLUSIONS: There was no detectable difference in hepatitis A seroprevalence between male homosexual and heterosexual GUM clinic attenders, despite a much higher level of oral-anal sexual activity among the homosexual population. PMID- 8001946 TI - Physicians' perceived value of international AIDS conferences and attitudes towards patient attendance. AB - OBJECTIVE: To determine the perceived value of attendance at an International AIDS Conference and attitudes towards the effect of patient attendance on the conference. DESIGN: A confidential, self-administered questionnaire. PARTICIPANTS: 102 physicians from the United Kingdom who attended the VIII International AIDS Conference in Amsterdam. RESULTS: There was an 84% response rate. 50% reported increased motivation for clinical work and 57% for research. Physicians with a lower HIV positive patient workload found the conference more valuable for finding out the latest information on HIV, compared with those with a higher workload (p = 0.04). Those with a higher patient workload found the conference more useful for increasing motivation for research than those with a lower HIV workload (p = 0.047). Conference attendance was felt to reduce burnout by 48% of respondents. The majority (55%) would prefer a more traditional meeting. Patient attendance was seen as improving the standard of discussion of ethical and political issues but not on medical or scientific issues. CONCLUSIONS: The International AIDS Conferences are perceived as useful by those UK physicians who attend, but most would prefer a more "traditional" scientific meeting. Whilst patient participation was not seen as useful for medical or scientific discussions, it was felt to improve discussion of ethical and political issues. A smaller more focused conference may be equally useful to UK physicians. PMID- 8001945 TI - Surveillance report: disease trends at New Zealand sexually transmitted disease clinics 1977-1993. AB - AIM: To document trends in sexually transmitted diseases (STDs) recorded by New Zealand STD Clinics from 1977-1993. METHODS: Clinic disease figures have been recorded since clinics commenced in the 1920s and were recorded in a comprehensive format from the 1970s. The New Zealand Venereological Society has collated these data since 1986. RESULTS: The most common STDs in New Zealand clinics are genital warts, non-specific genital infections, chlamydia and genital herpes. Genital Wart infection has been the commonest STD diagnosed in clinics since 1988 and occurred in 17.9% of new patients in 1993. Non Specific Genital Infections were the commonest diagnosis from 1977 to 1988 affecting 17.5% of new patients in 1993. Chlamydia has shown a fall since the mid 1980s diagnosed in 5.4% of new patients in 1993 compared with 14.6% in 1986. Gonorrhoea incidence has fallen steadily since 1975 affecting only 1.1% new patients in 1993. Genital Herpes numbers tripled from 1977 to 1993 and 54% are primary cases. HIV Disease has increased clinic workload greatly with screening and counselling conducted in 25% of new patients in 1993. HIV disease was diagnosed or managed in 0.2% new clinic patients (49 cases). Syphilis has remained at a low incidence in New Zealand diagnosed in 0.3% new patients in 1993. CONCLUSION: Attendance for the viral diseases, HIV disease, genital warts and genital herpes is increasing while for the bacterial diseases, gonorrhoea and chlamydia is decreasing. The rise in disease numbers since 1990 may be due to meeting service needs rather than a true rise in disease incidence. STD surveillance in New Zealand is improving with new reporting systems being developed. PMID- 8001947 TI - Doctor time requirement for patient consultation in genitourinary medicine clinics. PMID- 8001948 TI - Setting up regional audit in genitourinary medicine and HIV: the south east Thames experience. AB - Audit at regional level is a useful complement to local audit, especially in small specialties. Regional audit can reduce professional isolation and lead to the development of uniformly high standards in the care given by a variety of providers. The development of regional audit in genitourinary medicine in South East Thames (UK), and of HIV medicine in South Thames, is described. Meetings are held quarterly, and concentrate on standard setting and development of guidelines. Information about the practice of individual units is collected by questionnaire, the results presented, and guidelines developed. Participation in completing questionnaires and attending the meetings is good. Regional guidelines in eleven topics have been produced, and methods of auditing changes in practice are now being assessed. A regional common data-set is being developed to assist in the audit process. PMID- 8001949 TI - Mild balanoposthitis. AB - AIM: To identify and study cases of mild balanoposthitis (MBP) with penile pathology among patients observed at a dermatology clinic over an 18-month period. MATERIALS: The study included 321 patients with penile pathology. The term MBP was used to describe balanoposthitis of a localised, inflammatory nature with few, non-specific symptoms and a tendency to become chronic or recur. Two hundred and seventy had diseases clearly identifiable by clinical examination or laboratory tests; 51 cases were diagnosed as MBP and these patients had blood tests (to evaluate immune status) and microbiological examination; when these proved negative, a series of patch tests was also used. RESULTS: Of the 51 patients diagnosed as having MBP, the cause was ascertained in 34 cases (infection, mechanical trauma, contact irritation, contact allergy, etc.), whereas no specific aetiological factor was detected to explain the symptoms in the remaining 17 cases. PMID- 8001950 TI - Trichomicosis pubis: black variety. AB - A case of a 25 year old man with the black variety of trichomicosis pubis is presented on account of its extreme rareity. Scanning electron microscopy confirms that trichomicosis pubis is caused by bacterial colonisation of the pubic hair and shows that bacteria are able to penetrate cuticular horny cells directly through their free plasma membrane. PMID- 8001951 TI - The history of venereal disease and yaws (parangi) in Sri Lanka (Ceylon). PMID- 8001952 TI - High morbidity and mortality associated with non-AIDS defining conditions in HIV infected patients in Spain. PMID- 8001953 TI - Chlamydia trachomatis infection in males attending general practitioners. PMID- 8001954 TI - Genital ulceration secondary to Epstein Barr virus infection. PMID- 8001955 TI - Are doctors in genitourinary medicine clinics perceiving the psychological impact of recurrent genital herpes? PMID- 8001957 TI - Ciprofloxacin resistant gonococci arriving from Thailand. PMID- 8001956 TI - Human papillomavirus (HPV) DNA is not detected in the peripheral blood cells of patients with cervical carcinoma. PMID- 8001958 TI - Suitability of Neisseria gonorrhoeae lipooligosaccharides for epidemiological studies. PMID- 8001959 TI - Acute urinary retention preceding skin manifestations of genital herpes by 8 days. PMID- 8001960 TI - Infectious osteitis pubis in an HIV seropositive female. PMID- 8001961 TI - Mycoplasma genitalium: a cause of non-gonococcal urethritis? PMID- 8001962 TI - Assignment of a gene for autosomal recessive retinitis pigmentosa (RP12) to chromosome 1q31-q32.1 in an inbred and genetically heterogeneous disease population. AB - Linkage analysis was carried out in a large family segregating for autosomal recessive retinitis pigmentosa (arRP), originating from a genetically isolated population in The Netherlands. Within the family, clinical heterogeneity was observed, with a major section of the family segregating arRP with characteristic para-arteriolar preservation of the retinal pigment epithelium (PPRPE). In the remainder of the ar-RP-patients no PPRPE was found. Initially, all branches of the family were analyzed jointly, and linkage was found between the marker F13B, located on 1q31-q32.1, and RP12 (zmax = 4.99 at 8% recombination). Analysis of linkage heterogeneity between five branches of the family yielded significant evidence for nonallelic genetic heterogeneity within this family, coinciding with the observed clinical differences. Multipoint analysis, carried out in the branches that showed linkage, favored the locus order 1cen-D1S158-(F13B, RP12) D1S53-1qter (zmax = 9.17). The finding of a single founder allele associated with the disease phenotype supports this localization. This study reveals that even in a large family, apparently segregating for a single disease entity, genetic heterogeneity can be detected and resolved successfully. PMID- 8001963 TI - Fine genetic mapping of the gene for nevoid basal cell carcinoma syndrome. AB - Nevoid basal cell carcinoma syndrome (NBCCS, or Gorlin syndrome) is a cancer predisposition syndrome characterized by multiple basal cell carcinomas and diverse developmental defects. The gene responsible for NBCCS, which is most likely to be a tumor suppressor gene, has previously been mapped to 9q22.3-q31 in a 12-cM interval between the microsatellite marker loci D9S12.1 and D9S109. Combined multipoint and haplotype analyses of additional polymorphisms in this region in our collection of Australasian pedigrees have further refined the localization of the gene to between the markers D9S196 and D9S180, an interval reported to be approximately 2 cM. PMID- 8001964 TI - Mapping of the 12q12-q22 region with respect to tumor translocation breakpoints. AB - The consistent involvement of the region 12q13-q15 in numerous human tumors speaks in favor of the presence of genes that may contribute to oncogenesis. Mapping genes within this region of chromosome 12 is a necessary step toward the identification of those that play a role in this process. We have undertaken a multiplex analysis using translocation breakpoint mapping to order from the centromere to the telomere a series of 24 loci from the region 12q12-q22. Thirteen adipose tissue tumors with seven different chromosome changes involving the long arm of chromosome 12 (12q) were used. Since most of these loci are genes or anonymous DNA segments largely available to the scientific community, this map should be useful for investigation of genetic disorders associated with chromosome 12q. While these breakpoints were used as natural landmarks to order groups of loci, this work has positioned them more accurately, leading to a better chromosomal definition of the translocations than the one derived from standard cytogenetic studies. PMID- 8001965 TI - Structure of the human type-I interferon gene cluster determined from a YAC clone contig. AB - A map of the type-I interferon gene cluster located on the short arm of human chromosome 9 (9p) has been constructed using a contig of YAC clones. This map contains 26 interferon (IFN) genes and pseudogenes, and it accounts for all, except one, of the IFN sequences previously reported by other authors, plus a new IFNW pseudogene. The most distal gene on 9p is IFNB, and the most proximal one is IFNWP19. The direction of transcription for the 20 most distal IFN sequences is toward the telomere and for the 6 most proximal sequences, toward the centromere. Several regions of the cluster show evidence of ancestral duplication events. Some of these events may be explained by unequal crossing over between adjacent tandem genes. The location of several breakpoints within the cluster, from deletions associated with leukemias and gliomas, was also determined. PMID- 8001967 TI - Isolation of a yeast artificial chromosome contig spanning the Greig cephalopolysyndactyly syndrome (GCPS) gene region. AB - Disruption of the zinc finger gene GLI3 has been shown to be the cause of Greig cephalopolysyndactyly syndrome (GCPS), at least in some GCPS translocation patients. To characterize this genomic region on human chromosome 7p13, we have isolated a YAC contig of more than 1000 kb including the GLI3 gene. In this contig the gene itself spans at least 200-250 kb. A CpG island is located in the vicinity of the 5' region of the known GLI3 cDNA, implying a potential promoter region. PMID- 8001966 TI - Molecular cloning of a putative novel human bZIP transcription factor on chromosome 17q22. AB - We have cloned and characterized cDNA clones representing several mRNA isoforms generated by alternative splicing of a single gene localized to chromosome 17q22. Sequence analysis showed that the predicted translational product of the longest open reading frame (2316 nucleotides, 772 amino acids) is related to transcription factors of the basic leucine zipper (bZIP) class. The sequence contained several regions characteristic of transcriptional regulatory domains. A cluster of amino acids flanking the bZIP region on both sides was highly conserved between TCF11 and p45 NF-E2, a subunit of the human globin locus control region-binding protein, NF-E2. These same regions showed remarkable homology to two invertebrate proteins, CNC and skin-1, postulated to regulate embryonic development in Drosophila melanogaster and Caenorhabditis elegans, respectively. PMID- 8001968 TI - Physical analysis of the terminal 270 kb of DNA from human chromosome 1q. AB - DNA from three 1q44-derived human telomeric yeast artificial chromosome clones was analyzed using physical mapping methods. The smallest clone, yRM2004 (65 kb), corresponded exactly to the distal end of the largest clone, yRM2123 (270 kb). The third clone, yRM2192, overlapped with the proximal end of yRM2123 but not the distal end, suggesting that it is most likely a deletion artifact of a clone originally derived from a 1q telomere fragment. Data from fluorescence in situ hybridization analysis, restriction mapping, and RecA-assisted restriction enzyme cleavage experiments indicate that the molecular clone yRM2123 contains a 260-kb DNA fragment colinear with a genomic telomere-terminal fragment from 1q. yRM2123 contains low-copy subtelomeric and subterminal repeats at its distal end, single copy DNA more centromerically, and a CG-rich region with homology to mouse DNA. Markers derived from this clone will allow telomeric closure of the physical and genetic linkage maps of human chromosome 1q. PMID- 8001969 TI - Parallel evolutionary events in the haptoglobin gene clusters of rhesus monkey and human. AB - Parallel occurrences of evolutionary events in the haptoglobin gene clusters of rhesus monkeys and humans were studied. We found six different haplotypes among 11 individuals from two rhesus monkey families. The six haplotypes include two types of haptoglobin gene clusters: one type with a single gene and the other with two genes. DNA sequence analysis indicates that the one-gene and the two gene clusters were both formed by unequal homologous crossovers between two genes of an ancestral three-gene cluster, near exon 5, the longest exon of the gene. This exon is also the location where a separate unequal homologous crossover occurred in the human lineage, forming the human two-gene haptoglobin gene cluster from an ancestral three-gene cluster. The occurrence of independent homologous unequal crossovers in rhesus monkey and in human within the same region of DNA suggests that the evolutionary history of the haptoglobin gene cluster in primates is the consequence of frequent homologous pairings facilitated by the longest and most conserved exon of the gene. PMID- 8001970 TI - Integration of gene maps: chromosome X. AB - Omitting 1137 loci that are included in the location database but have only cytogenetic assignment, there are 605 loci in the integrated map that synthesizes physical and genetic data and subsumes a composite physical location, cytogenetic and regional assignments, mouse homology, rank, and references. With error filtration and allowance for interference the genetic length is 211 cM, to which the p arm contributes 100 cM. The physical length is 164 Mb, with 62 Mb in the p arm. Current problems in map integration are discussed and some solutions proposed. PMID- 8001971 TI - Molecular cloning and physical and genetic mapping of the human anion exchanger isoform 3 (SLC2C) gene to chromosome 2q36. AB - A human clone corresponding to the gene encoding anion exchanger isoform 3 (AE3) (approved gene symbol SLC2C) has been isolated and partially sequenced. Oligonucleotide primers based on this sequence were used in a polymerase chain reaction to specifically amplify a segment of the human gene from a panel of human-rodent somatic cell hybrids, allowing the assignment of AE3 to chromosome 2. To map AE3 more precisely to a cytogenetic band on chromosome 2, the AE3 cosmid was used as a probe in fluorescence in situ hybridization to human metaphase chromosomes. Fractional length measurements were made, and AE3 mapped at high resolution to the cytogenetic band 2q36. A polymorphic dinucleotide (GT/CA)n repeat marker was developed from sequences in the AE3 cosmid and typed on a subset of the CEPH families. Multipoint linkage analysis placed the AE3 gene between D2S128 and D2S126 on a genetic map of chromosome 2, corroborating the chromosomal localization of AE3 obtained by physical mapping methods. PMID- 8001972 TI - Molecular analysis of mouse Rab11b: a new type of mammalian YPT/Rab protein. AB - Since the realization that the vesicular transport machinery is conserved from yeast to vertebrate neurons, much interest in the proteins involved has been generated. Here we describe a new type of mammalian YPT/Rab protein, named Rab11b, that is most abundantly expressed in brain, heart, and testis. It has all the hallmarks of a YPT3/Rab11 protein, but is more closely related to a ypt3 related gene isolated from fish (97% homology) than to the previously described four mammalian Rab11 genes (89% homology). The mammalian Rab11 genes discovered previously are, by contrast, 100% identical to each other. The genomic structure of a mammalian Rab11 protein is described for the first time. It is surprisingly asymmetrical, with 96% of the coding sequence contained in one-third of the transcription unit. Two copies of this gene are mapped to mouse chromosomes 1 and 17. The fine structural analysis of Rab11b and the protein sequence comparison provides a close look at all YPT3/Rab11-related genes cloned so far and clues to their possible relationship. PMID- 8001973 TI - Construction of a high-resolution linkage map for Xp22.1-p22.2 and refinement of the genetic localization of the Coffin-Lowry syndrome gene. AB - The genes responsible for two X-linked diseases, the Coffin-Lowry syndrome (CLS) and juvenile retinoschisis (RS), have been previously mapped, through linkage studies, to an 8-cM region, in Xp22.1-p22.2, flanked distally by two tightly linked markers, DXS207 and DXS43, and proximally by DXS274. In the present study, five Genethon markers have been assigned to the (DXS207, DXS43)-DXS274 interval using somatic cell hybrids and a meiotic breakpoint panel and ordered together with three markers previously mapped to this region. A genetic map, which includes 13 loci and spans a distance of approximately 13 cM, was derived from linkage analysis using the CEPH families. The most likely locus order and map distances (in centimorgans) are Xpter-DXS16-(3.4)-(DXS207, DXS43, DXS1053)-(2.0) (DXS999, DXS257)-(1.7)-AFM291 wf5-(1.4) - DXS443 - (2.0) - (DXS1229, DXS365) - (2.1) - (DXS1052, DXS274, DXS41)-Xcen. Analysis of multiply informative crossovers established AFM291 wf5 and DXS1052 as new flanking markers for CLS, which significantly reduces the candidate region for this disease gene to a 4- to 5-cM interval. Three markers, DXS443, DXS1229, and DXS365, mapping within this interval showed complete cosegregation with the disease phenotype, giving a multipoint lod score of 14.2. The present map provides the framework for constructing a YAC contig for the CLS and RS region and should be useful for refining the localization of other disease genes mapping to this region. The panel of somatic cell hybrids characterized for the present study has also allowed us to refine the localization of five genes (CALB3, GRPR, PDHA1, GLRA2, and PHKA2) and two expressed sequence tags (DXS1118E and DXS1006E) previously assigned to the Xp22 region. PMID- 8001974 TI - Syntenic assignment of human chromosome 1 homologous loci in the bovine. AB - Three mouse chromosomes (MMU 1, 3, and 4) carry homologs of human chromosome 1 (HSA 1) genes. A similar situation is found in the bovine, where five bovine chromosomes (BTA 2, 3, 5, 16, and unassigned syntenic group U25) contain homologs of HSA 1 loci. To evaluate further the syntenic relationship of HSA 1 homologs in cattle, 10 loci have been physically mapped through segregation analysis in bovine-rodent hybrid somatic cells. These loci, chosen for their location on HSA 1, are antithrombin 3 (AT3), renin (REN), complement component receptor 2 (CR2), phosphofructokinase muscle type (PFKM), Gardner-Rasheed feline sarcoma viral (v fgr) oncogene homolog (FGR), alpha fucosidase (FUCA1), G-protein beta 1 subunit (GNB1), alpha 1A amylase, (AMY1), the neuroblastoma RAS viral (v-ras) oncogene homolog (NRAS), and alpha skeletal actin (ACTA1). AT3, REN, CR2, and GNB1 mapped to BTA 16, PFKM to BTA 5, AMY1A and NRAS to BTA 3, FGR and FUCA1 to BTA 2, and ACTA1 to BTA 28. PMID- 8001975 TI - The mouse and human excitatory amino acid transporter gene (EAAT1) maps to mouse chromosome 15 and a region of syntenic homology on human chromosome 5. AB - The gene for human excitatory amino acid transporter (EAAT1) was localized to the distal region of human chromosome 5p13 by in situ hybridization of metaphase chromosome spreads. Interspecific back-cross analysis identified the mouse Eaat1 locus in a region of 5p13 homology on mouse chromosome 15. Markers that are linked with EAAT1 on both human and mouse chromosomes include the receptors for leukemia inhibitory factor, interleukin-7, and prolactin. The Eaat1 locus appears not to be linked to the epilepsy mutant stg locus, which is also on chromosome 15. The EAAT1 locus is located in a region of 5p deletions that have been associated with mental retardation and microcephaly. PMID- 8001976 TI - Assignment of the human homologue of the mTRiC-P5 gene (TRIC5) to band 1q23 by fluorescence in situ hybridization. AB - The TCP1 ring complex (TRiC) is a molecular chaperone involved in actin and tubulin folding. Little is known about the components of this complex. The first component identified was TCP1, a protein coded by a gene in the t-complex locus on mouse chromosome 17. This locus is involved in several embryonic defects, male sterility, and the transmission ratio distortion. In humans, the t-complex genes map to chromosome 6. Other components of TRiC are thought to be TCP1-related proteins. Recently, a mouse cDNA coding for one of these proteins has been cloned and named mTRiC-P5. Here we report the cloning of a partial human cDNA clone, homologous to mTRiC-P5, and its chromosome localization by fluorescence in situ hybridization. The human TRiC-P5 gene (TRIC5) maps to human chromosome 1q23, a region known to be a preferential chromosomal breakpoint involved in leukemia. Therefore, even if TCP1 and TRiC-P5 are related proteins and are found in the same protein complex, they are not coded by syntenic genes in humans. PMID- 8001977 TI - Assignment of the gene encoding the 5-HT1E serotonin receptor (S31) (locus HTR1E) to human chromosome 6q14-q15. AB - The human gene for the 5-HT1E serotonin receptor was recently cloned, but no chromosomal assignment has yet been given to this gene (locus HTR1E). In this work, we demonstrate by two independent polymerase chain reactions on a panel of human-hamster somatic cell hybrid genomic DNA that the 5-HT1E serotonin receptor gene is localized on human chromosome 6. Furthermore, by means of in situ hybridization to human metaphase chromosomes, using the cloned 5-HT1E receptor gene (phage clone lambda-S31; Levy et al., FEBS Lett. 296:201-206,1992) as was a probe, we demonstrate that this gene is localized to the q14-q15 region on chromosome 6. Screening of genomic DNA from 15 unrelated Caucasian individuals, using as a probe the open reading frame of the cloned 5-HT1E receptor gene, did not reveal any restriction fragment length polymorphisms with the enzymes BamHI, BanII, BglII, EcoRI, HincII, HindIII, HinfI, MspI, PstI, and PvuII. Since the 5 HT1E receptor is found mainly in the cerebral cortex and abnormal function of the serotonergic system has been implicated in a variety of neurologic and psychiatric diseases, the precise chromosomal assignment of the 5-HT1E receptor gene is the crucial first step toward the evaluation of this locus as a candidate for mutations in such syndromes. PMID- 8001978 TI - The first intron of human c-fms proto-oncogene contains a processed pseudogene (RPL7P) for ribosomal protein L7. AB - During sequence analysis of the first intron of the human c-fms oncogene, we identified an open reading frame encoding the ribosomal protein L7 (RPL7). The presence of this sequence within intron 1 of the c-fms gene was confirmed by Southern blot hybridization and by sequence analysis of two independent cosmid clones (cos2-e and cos1-22) that span the human genomic c-fms locus. The RPL7 sequence was detected in a region of sequence overlapped by the cos2-e and cos1 22 cosmid clones but oriented opposite to the c-fms gene. We demonstrated that the sequence is identical to the full-length RPL7 cDNA sequence, but lacks any recognizable introns, has a 30-bp poly(A) tail, and is bracketed by two perfect direct repeats of 14 bp. We also showed that despite the fact that the 5' flanking region of the RPL7 sequence contains a potential TATA box upstream of an intact open reading frame, this pseudogene (RPL7P) is not actively transcribed. PMID- 8001979 TI - Genetic and physical mapping of a gene encoding a methyl CpG binding protein, Mecp2, to the mouse X chromosome. AB - The methyl CpG binding proteins (MeCP1 and MeCP2) are a class of proteins that bind to templates containing symmetrically methylated CpGs. Using an interspecific backcross segregating a number of X-linked markers, we have localized the Mecp2 gene in mouse to the X chromosome close to the microsatellite marker DXMit1. Detailed physical mapping utilizing an available YAC contig encompassing the DXMit1 locus has localized the Mecp2 gene to a 40-kb region between the L1cam and the Rsvp loci, indicating the probable position of a homologue on the human X chromosome. PMID- 8001981 TI - The murine homeobox genes Nkx2.3 and Nkx2.6 are located on chromosomes 19 and 14, respectively. PMID- 8001980 TI - Morquio A syndrome: cloning, sequence, and structure of the human N acetylgalactosamine 6-sulfatase (GALNS) gene. AB - Deficiency of the lysosomal enzyme, N-acetylgalactosamine 6-sulfatase (GALNS;EC 3.1.6.4), results in the storage of the glycosaminoglycans, keratan sulfate and chondroitin 6-sulfate, which leads to the lysosomal storage disorder Morquio A syndrome. Four overlapping genomic clones derived from a chromosome 16-specific gridded cosmid library containing the entire GALNS gene were isolated. The structure of the gene and the sequence of the exon/intron boundaries and the 5' promoter region were determined. The GALNS gene is split into 14 exons spanning approximately 40 kb. The potential promoter for GALNS lacks a TATA box but contains GC box consensus sequences, consistent with its role as a housekeeping gene. The GALNS gene contains an Alu repeat in intron 5 and a VNTR-like sequence in intron 6. PMID- 8001982 TI - Assignment of the human macrophage mannose receptor gene (MRC1) to 10p13 by in situ hybridization and PCR-based somatic cell hybrid mapping. PMID- 8001983 TI - Nonallelic heterogeneity in autosomal dominant retinitis pigmentosa with incomplete penetrance. PMID- 8001984 TI - Localization of the human cytoplasmic dynein heavy chain (DNECL) to 14qter by fluorescence in situ hybridization. PMID- 8001986 TI - Localization of serum biotinidase (BTD) to human chromosome 3 in band p25. PMID- 8001985 TI - Assignment of the human cytidine deaminase (CDA) gene to chromosome 1 band p35 p36.2. PMID- 8001987 TI - A 2-Mb YAC contig linking the plasminogen-apoprotein(a) gene family to the insulin-like growth factor 2 receptor (IGF2R) gene on the telomeric region of chromosome 6 (6q26-q27). PMID- 8001988 TI - Multiple current dipole estimation using simulated annealing. AB - A method for estimating electrical current distribution in the human brain using a multiple current dipole model is presented. A cost function for estimating multiple dipoles is proposed and a simulated annealing algorithm is used to obtain an acceptable solution. Computer simulation is used to evaluate the effectiveness of this method. PMID- 8001989 TI - Finite element models of thoracic conductive anatomy: sensitivity to changes in inhomogeneity and anisotropy. AB - A moderately detailed 3-D finite element model of the conductive anatomy of a canine thorax was used to examine the sensitivity of the results obtained during simulated transthoracic defibrillation to variations in skeletal muscle anisotropy and differing degrees of model inhomogeneity. Our results suggest that the myocardial current density distribution is not particularly sensitive to the method used to model skeletal muscle anisotropy. However, anisotropy variations caused defibrillation parameters such as paddle to paddle impedance and threshold current to change by as much as 50%. We found a greater sensitivity in the myocardial current density and the defibrillation parameters to variations in model inhomogeneity. The changes observed in both depended substantially on paddle placement. This sensitivity to paddle placement highlights the difficulty in predicting how a reduction in anatomical detail will affect the myocardial current density distribution. In general, we found the defibrillation parameters to be more sensitive than the myocardial current density distribution to the variations in anatomical detail we examined. PMID- 8001990 TI - Induced electric currents in models of man and rodents from 60 Hz magnetic fields. AB - Induced electric currents in models of man, rat and mouse from 60 Hz magnetic fields are computed using the impedance method. The models all have realistic shapes, and in the case of rodents, a homogeneous average tissue conductivity is assumed. The model of man is analyzed for two cases, a homogeneous average tissue conductivity and a heterogeneous model, both consisting of 1.3 cm cubical tissue cells whose conductivities are representative of the tissue within the cube. The results for various models and species, as well as different orientations of the magnetic field, are compared. The data presented are useful as the first step in dosimetry for 60 Hz magnetic fields, and for interspecies scaling of biological interactions related to the tissue induced electric currents. PMID- 8001991 TI - Toward functional magnetic stimulation (FMS) theory and experiment. AB - This paper examines the use of magnetic fields to functionally stimulate peripheral nerves. All electric fields are induced via a changing magnetic field whose flux is entirely confined within a closed magnetic circuit. Induced electric fields are simulated using a nonlinear boundary element solver. The induced fields are solved using duality theory. The accuracy of these predictions is verified by saline bath experiments. Next, the theory is applied to the stimulation of nerves using small, partially occluded ferrite and laminated vanadium permendur cores. Experiments demonstrate the successful stimulation of peripheral nerves in the African bullfrog with 11 mA, 153 mV excitations. These results offer a new vista of possibilities in the area of functional nerve stimulation. Unlike functional electric stimulation (FES), FMS does not involve any half cell reactions, and thus would not have the commensurate FES restrictions regarding balanced biphasic stimulation, strength duration balances, and oxidation issues, always exercising care that the electrodes remain in the reversible operating regime. PMID- 8001992 TI - AR modeling of myoelectric interference signals during a ramp contraction. AB - We investigated the time-varying behaviour of the autoregressive (AR) parameters in a myoelectric (ME) signal detected during a linear force increasing contraction. The AR parameters of interest were the reflection coefficients, the AR model spectrum, and the prediction errors. We used well-conditioned ME signals for which the complete time record of the motor units firings was available. In addition, the influence of the recruitment of a new motor unit, the conduction velocity of action potentials, and additive broad-band noise were investigated using simulated ME signals. The simulated ME signals were constructed from a selected group of the available motor unit action potential trains. The results revealed that, as the contraction progressed, the AR parameters displayed a time varying behavior which coincided with the recruitment of newly recruited motor units whose spectrum of the waveform differed from that of the rest of the ME signal. This property of the AR parameters was obscured by the presence of broad band noise and low-amplitude motor unit action potentials, both of which are more pronounced during low-level force contractions. PMID- 8001993 TI - NNERVE: neural network extraction of repetitive vectors for electromyography- Part I: Algorithm. AB - Artificial neural network (ANN) based signal processing methods have been shown to have significant robustness in processing complex, degraded, noisy, and unstable signals. A novel approach to automated electromyogram (EMG) signal decomposition, using an ANN processing architecture, is presented in this paper. Due to the lack of a priori knowledge of motor unit action potential (MUAP) morphology, the EMG decomposition must be performed in an unsupervised manner. An ANN classifier, consisting of a multilayer perceptron neural network and employing a novel unsupervised training strategy, is proposed. The ANN learns repetitive appearances of MUAP waveforms from their suspected occurrences in a filtered EMG signal in an autoassociative learning task. The same training waveforms are fed into the trained ANN and the output of the ANN is fed back to its input, giving rise to a dynamic retrieval net classifier. For each waveform in the data, the network discovers a feature vector associated with that waveform. For each waveform, classification is achieved by comparing its feature vector with those of the other waveforms. Firing information of each MUAP is further used to refine the classification results of the ANN classifier. Then, individual MUAP waveform shapes are derived and their firing tables are created. PMID- 8001995 TI - Time-varying adaptive filters for evoked potential estimation. AB - Adaptive implementation of an optimal time-varying filter (TVF) for evoked potential (EP) estimation is addressed in this paper. A data-adaptive scheme is used, which converges asymptotically to the optimal TVF solution. Two basic adaptive TVF's (ATVF's) are first introduced, namely least mean square (LMS) ATVF and recursive least-squares (RLS) ATVF. The latter converges much faster than the former. Since the basic ATVF's usually require a relatively large set of response trials to get a meaningful solution, a reduced-order ATVF is further presented and the corresponding LMS and RLS (including a fast RLS) adaptive algorithms are developed. To save memory, a truncated Fourier expansion is suggested to express approximately the time-sequenced weight-vectors of the ATVF's, resulting in a simplified reduced-order ATVF. Finally, extensive simulations are provided to confirm the superior performance of the ATVF's. The present ATVF's can be used as prefilters for latency-corrected average (LCA) processing to obtain more informative estimates of EP signals. PMID- 8001994 TI - NNERVE: neural network extraction of repetitive vectors for electromyography- Part II: Performance analysis. AB - We have presented a new method for the decomposition of clinical electromyographic signals, NNERVE, which utilizes a novel "pseudo-unsupervised" neural network approach to signal decomposition. In this paper, we present a detailed performance analysis. We present definitions for quantitative performance criteria. NNERVE is shown to be highly reliable over a wide range of neural network architectures. It is also minimally sensitive to learning parameters. The degradations of performance over a wide range of signals and parameters are shown to be gradual, slight and graceful. These characteristics are shown to translate directly into a high degree of robustness over widely varying signals. Real signals obtained from the entire range of patients encountered in clinical situations are shown to be correctly handled without any modifications or adjustments of any parameters. This neural network method is then directly compared to a prior traditional signal processing method and is shown quantitatively to have consistently superior performance on both simulated and real signals. Clinically acceptable performance over a wide range of signals, recorded using standard clinical methodology, and the lack of a need for user interaction, will facilitate the use of motor unit quantitation in routine clinical electromyography. PMID- 8001996 TI - Peak component latency-corrected average method for evoked potential waveform estimation. AB - A peak component latency-corrected average (PC-LCA) method consisting of three steps is presented for estimating the evoked potentials (EP) in the human brain. The present PC-LCA is essentially an alternative version of the original LCA method developed by McGillem et al. It first uses a time-varying adaptive filter as a preprocessor to suppress the ongoing EEG and to enhance the EP. Then, the statistics of mean latencies and amplitudes of the EP peak components are estimated by a peak detection and alignment procedure. The final waveform estimate is obtained by superimposing the estimated mean peak components on background information and subsequently fitting a truncated Fourier series using the fast Fourier transform (FFT). Consistent estimates of the EP peak component information are established based on asymptotic analysis of the PC-LCA. Finally, real-time implementation of the PC-LCA is considered, and the superior performance of the PC-LCA method is confirmed by detailed numerical results. PMID- 8001997 TI - Accommodation of time delay variations in automatic infusion of sodium nitroprusside. AB - A new self-tuning regulator for control of mean arterial blood pressure using sodium nitroprusside is presented. In addition to adapting to various patient response gains and time constants, the controller can accommodate variations in pure time delays, a problem that has not been addressed fully in previously proposed controllers. The control algorithm derivation is based on incorporating a self-tuning controller with an adaptive discrete time delay compensator. The derivation, however, is general and can potentially be applied to other pharmacological agents in addition to sodium nitroprusside. The a priori information required for implementation of the controller is the estimate of the order of the patient response transfer function and the range of the pure time delay. An attractive feature of the controller is its capability to optimize the level of the infused drug during the transient phase of the control without creating an output offset. This feature tends to reduce the overall level of the infused drug. Hence, it may be useful when the cost of a drug or its long-term administration side effects is of concern, such as in the case of sodium nitroprusside. PMID- 8001998 TI - Modeling of magnetic field stimulation of bent neurons. AB - We consider a simple model of magnetic stimulation of a long bent neuron located in a semi-infinite volume conductor with a planar interface. It is shown that the stimulating coil characteristics (size, shape and location) and the neuron shape affect the location of the stimulation. The activating function, defined as the electric field derivative along the neuron, has two components. One component depends on the derivative of the electric field along the straight section of the neuron, and the other on the field magnitude. The maximal stimulation point is at the bent part of the nerve and its position depends on the nerve shape and coil parameters. The analysis also has shown a better performance (a stronger stimulus) for a double-circular (figure eight) coil than for a double-square coil. PMID- 8001999 TI - No touch pulse measurement by optical interferometry. AB - Arterial pulsatility was measured using an optical interferometer. As opposed to laser Doppler flow meters, the prototype system we evaluated can detect pulsation profiles of major arteries with potentially useful information including pulse wave velocity, profile of pulse pressure, etc. PMID- 8002000 TI - Continuous current source inversion of evoked potential fields in a spherical model head. AB - This study explores the efficacy of a physiological constraint on cortical current generators in promoting a robust solution for the inverse problem in evoked potentials. It is proposed that the current sources responsible for the evoked potential be modeled as a set of dipoles oriented orthogonal to the surface of the cortex. Rather than using a minimum norm approach, the solution space is searched for a vector that minimizes the error of the predicted evoked potential scalp field. PMID- 8002001 TI - Channeling of the intermediates and catalytic facilitation to Rubisco in a multienzyme complex of Calvin cycle enzymes. AB - Calvin cycle multienzyme complex, consisting of phosphoriboisomerase, phosphoribulokinase and ribulose-1,5-bisphosphate carboxylase (Rubisco), shows ribose-5-phosphate + ATP dependent CO2 fixation activity with a small but discernible lag. Transient time analysis showed that the lag at pH 7 was independent of multienzyme concentration and was significantly lower than the expected transient time calculated from Km and Vmax of the individual enzymes, indicative of channeling of the intermediates in the enzyme complex. Channeling of ribulose-1,5-bisphosphate was found to offer a catalytic advantage to Rubisco. Rubisco shows a decrease in activity during catalysis in ribulose-1,5 bisphosphate dependent CO2 fixation reaction, due to the formation of the catalytic inhibitor. Such a decrease of Rubisco activity was not observed in ribose-5-phosphate + ATP dependent CO2 fixation reaction and the catalytic inhibitor was also not detected. These results suggested that the intermediates are channeled in the complex and channeling offers a catalytic facilitation to Rubisco. PMID- 8002002 TI - T cell responses in Hodgkin's disease: frequency distribution of IL-2 producing cells and quantitation of IL-2 produced per cell. AB - T cell dysfunction in Hodgkin's disease (HD) is well documented. Since interleukin-2 (IL-2) plays a pivotal role in T cell proliferation, we have investigated frequency distribution of IL-2 producing phytohaemagglutinin (PHA) stimulated lymphocytes from HD patients compared to that of healthy donors using two limiting dilution (LD) culture systems in which autologous peripheral blood lymphocytes (PBL) and Epstein Barr Virus transformed allogeneic B lymphoblastoid cell lines (EBV-LCL) have been used as feeders. The latter provided better conditions for IL-2 production by single cells, as evident from the enhanced frequencies obtained (For healthy donors: 1/67 +/- 1545.5 using EBV-LCL and 1/1123 +/- 1.7438 using autologous PBL as feeders). The data showed significantly reduced frequency of IL-2 producing cells as well as reduced quantity of IL-2 produced per cell in HD even after using/EBV-LCL as feeders, the amount of IL-2 produced per activated responder cell in HD patients being 0.825-1.3 pg/well (p < 0.001) as compared to 1.48-2.43 pg/well in healthy donors. Thus, the EBV-LCL feeders did provide better culture conditions for estimating frequencies of functional T cells. However these cell lines were unable to restore in vitro the abnormalities in functional properties of T cells in HD. PMID- 8002003 TI - Characterization of DNA polymerase-alpha/primase complex from developing embryonic chicken brains. AB - DNA polymerase-alpha and primase activities present in a complex, have been isolated, partially purified, and characterized from embryonic chicken brain. DNA polymerase-alpha activity, characterized by its sensitivity to N-ethyl-maleimide, high sedimentation coefficient (11.3 S), and acidic isoelectric point (5-5.5) was found in all embryonic ages. Primase activity, the enzyme responsible for the initiation of DNA synthesis, co-sedimented with DNA polymerase-alpha activity on a continuous glycerol velocity gradient. A complex containing both DNA polymerase alpha and primase activities was isolated by DE-23 cellulose column chromatography of cell-free extracts of different embryonic ages of chicken brain. In addition to the primase complexed with DNA polymerase-alpha, a free primase activity was isolated by DE-23 cellulose column chromatography of an ammonium sulfate (0-45%; w/v) precipitated fraction of embryonic chicken brain cell-free extract. DNA polymerase-alpha activity from developing chicken brains in the embryonic stage was purified by immuno-affinity column chromatography. Of all the single-stranded DNA templates tested, primase activity was found to be maximally active with poly dC. Primase activity was not inhibited by a high concentration of alpha-amanitin. The results obtained may provide insight into further understanding of regulation of chromosomal DNA replication in developing tissues. PMID- 8002004 TI - Mechanism of action of an eukaryotic initiation factor-2 (eIF-2) associated 67 kDa glycoprotein (p67) and an eIF-2 kinase (dsI). AB - Mechanism of regulation of eIF-2 alpha-subunit phosphorylation by dsI and p67 was studied. The results are as follows: (1) At low dsI concentration, p67 protected equimolar concentration of eIF-2. (2) At high dsI concentration, dsI efficiently phosphorylated eIF-2 alpha-subunit even when equimolar concentrations of both p67 and eIF-2 were present. Significantly increased p67 concentration was necessary to protect eIF-2 alpha-subunit at high dsI concentration. (3) dsI was also phosphorylated as it phosphorylated eIF-2 alpha-subunit. p67 inhibited both eIF-2 alpha-subunit and dsI phosphorylation similarly. (4) Although the [32P]-labelled dsI formed during the reaction could be effectively chased upon subsequent addition of excess unlabelled eIF-2 and ATP, the [32P] labelled eIF-2 formed under identical conditions, retained most of the radioactivity. (5) dsI coimmunoprecipitated with three subunit eIF-2 and p67 inhibited this coimmunoprecipitation reaction. It has been proposed: Three subunit eIF-2 and free p67 are in equilibrium with eIF-2 bound to p67 and, eIF-2.p67 complex is resistant to dsI phosphorylation. Activated dsI is already phosphorylated. At high concentration, dsI(P) can bind to free three subunit eIF-2 and form eIF 2.dsI(P) complex. dsI(P) in this complex then transfers its phosphoryl residue to eIF-2 and forms eIF-2 alpha(P) in an irreversible reaction. In a subsequent reaction, unphosphorylated dsI is autophosphorylated using [gamma 32P]-ATP and the cycle continues. Inhibition of eIF-2 alpha-subunit phosphorylation by p67 blocks this phosphorylation cycle and consequent dsI phosphorylation. PMID- 8002005 TI - Overexpression of Escherichia coli single stranded DNA binding protein under bacteriophage T 7 promoter. AB - A recombinant vector for overproduction of the E. coli single stranded DNA binding protein (E. coli SSBP) has been constructed. An E. coli strain carrying this plasmid produces up to 150 mg pure SSBP per litre of bacterial culture in a laboratory shake flask. Electron microscopy of the single stranded DNA complexed with SSBP shows characteristic "beaded string"-like appearance. Strong clustering of protein molecules on ssDNA is indicative of a highly cooperative binding. PMID- 8002006 TI - Facile formation of heteromultimeric potassium channels by expression of cloned human cDNAs. AB - Complementary DNAs representing three voltage-gated potassium channels of human origin have previously been expressed in Xenopus laevis oocytes by injecting RNA transcribed in vitro [Ramaswami, M., Gautam, M., Kamb, A., Rudy, B., Tanouye, M. A. & Mathew, M. K. (1990) Mol. Cell. Nueorsci 1, 214-223]. We have coinjected RNAs for pairs of K(+)-channel genes into Xenopus oocytes. Analysis of the kinetics of the evoked currents, their voltage dependence and pharmacological sensitivities demonstrate that channels formed on coinjection of RNA pairs have properties distinct from those evoked by either channel type alone. We conclude that these currents arise from heteromultimeric aggregates of the subunits encoded by the individual RNAs. Quantitative analysis of the currents indicate that at least 60% of the current seen can be ascribed to heteromultimeric channels demonstrating their facile formation. Given that there are a large number of primary transcripts present in the nervous system, the demonstration of pharmacologically distinct heteromultimers may complicate the extension of studies on single, cloned K(+)-channels in heterologous systems to neuronal cells. PMID- 8002007 TI - Oxidative damage to the eye lens caused by cigarette smoke and fuel smoke condensates. AB - Cigarette smoking is reported to increase the risk of cataract. Likewise, the use of smoky cooking fuel is implicated in the etiology of cataract. In an effort to understand the cellular and molecular basis, the in vitro and in vivo cataractogenetic effects of these smoke condensates have been studied using isolated rat lenses and pigmented rats. Isolated capsulated rat lenses are incubated with cigarette smoke condensate (CSC) and firewood smoke condensate (FSC) for varying periods, with and without antioxidants, in the presence and absence of light. CSC and FSC permeate the lens capsule, impart colour and opacify the lens in a light- and dose-dependent manner. Antioxidants offer partial inhibition against the above damage. The condensates contain polycyclic aromatics which generate reactive oxygen species such as O2 photodynamically, and ppb levels of Fenton metal ions which induce oxidative reactions through .OH. Smoke induced damage possibly occurs through systemic absorption and transport of toxic components to several tissues, and specially into the lens, wherein the turnover is slow, leading to chronic accumulation causing oxidative damage to the constituent molecules and to consequent lenticular opacity. PMID- 8002008 TI - Role of alkali cations (K+ and Na+) in cyanobacterial nitrogen fixation and adaptation to salinity and osmotic stress. AB - Cyanobacteria occupy almost every possible ecological niche on earth, being tolerant to a large number of environmental stresses, including salinity and drought. Many of them also fix atmospheric nitrogen. They are responsible for a significant share of biosolar energy conversions on this planet and make substantial contributions to the carbon and nitrogen status of both oceans and soils. Sodium and potassium are two of the most prevalent cations on this planet. While K+ is an essential macronutrient in most life-forms, Na+ is strongly discriminated by means of highly selective alkali cation transport systems, favouring K+ over Na+. Although a nutritional requirement for K+ has not been specifically investigated, rapid accumulation of K+ during salt/osmotic stress has been observed in several cyanobacteria. Genes and proteins constituting a membrane-bound, turgor- and osmo-inducible, Kdp-ATPase-like system in Anabaena strains that may help in their early K+ responses to salt/osmotic stress have been identified. An unusual, specific and absolute requirement for trace quantities of sodium has been documented in cyanobacteria. Work done in our laboratory, and elsewhere, has elucidated the mechanisms underlying such a unique requirement. It has long been believed that cyanobacteria scavenge and immobilise sodium. We have, however, shown that sodium exclusion brought about by curtailment of influx and active efflux of Na+ forms the basis of salt tolerance in these microbes and that the inherent salt tolerance can be modified by factors that modulate Na+ fluxes in cyanobacteria. Identification of genes affecting the cation relationships in nitrogen-fixing cyanobacteria is currently in progress. PMID- 8002009 TI - Structural organization, amplification, deletion and rearrangements of DNA sequences associated with an unstable region of the chromosome of Streptomyces coelicolor A3(2). AB - The chromosome of Streptomyces coelicolor A3(2) carries unstable DNA sequences hybridising with DNA sequences from an unstable chromosomal region of the related species S. lividans. These S. coelicolor sequences are nearly identical to those of S. lividans TK23 in organisation but differ from those of S. lividans 66 TK64 which harbours a tandem duplication of these sequences. Southern hybridisations using heterologous probes and S. coelicolor DNA cleaved with a variety of restriction enzymes permitted us to construct a partial restriction map of the unstable region of the chromosome of S. coelicolor. Genetic analysis shows that the unstable region yields distinguishable variants with several distinct DNA rearrangements. PMID- 8002010 TI - Development of a 23S rRNA-based PCR assay for the detection of mycobacteria. AB - The partial nucleotide sequence of a recombinant plasmid containing the 23S rRNA gene of Mycobacterium tuberculosis was determined and an assay was developed for amplifying 23S rRNA gene sequences of mycobacteria. The PCR-based non-radioactive test enabled us to distinguish Mycobacterium from other closely related genera and was sensitive enough to detect 2 bacterial genome equivalents. The assay was extended to the detection of mycobacterial DNA in uncultured clinical specimens; 23S rRNA sequences were detected in thirty four of forty eight (70.8%) sputum and cerebrospinal fluid (CSF) specimens by the PCR assay, whereas direct smear examination and culture methods demonstrated a positivity rate of 29.2% and 16.7% respectively for the same specimens. A RNA-based PCR assay with a detection limit of 1 genome equivalent was also developed. These PCR assays should prove useful for the early and rapid detection of mycobacterial infection in uncultured clinical specimens. PMID- 8002011 TI - Differentiation of mouse embryonal carcinoma cells PCC4 by heat shock and the kinetics of induction of heat shock proteins. AB - Heat shock to embryonal carcinoma cells PCC4 at 45 degrees C for 30 min resulted in the differentiation of cells although heat shock response was induced on exposure to 42 degrees C for 60 min. Differentiated cells were large and well spread with reduced nuclear/cytoplasmic ratios as compared to undifferentiated cells. Change in cell morphology was associated with the disappearance and appearance of stage specific embryonic antigens 1 and 3 respectively. We also found a change in intracellular pH in PCC4 cells within 30 min of heat shock as measured by the change in fluorescence intensity of a probe incorporated into cells during heat shock. PMID- 8002012 TI - Construction and characterization of M13 bacteriophages displaying gp120 binding domains of human CD4. AB - The envelope glycoprotein, gp120, on the surface of HIV interacts with the human CD4 molecule and thus helps the virus in gaining entry into the T-helper cells. To display the gp120 binding domains of human CD4 on the surface of the bacteriophage M13, two types of vectors have been constructed. In these, the first 176 amino acids of the human CD4 have been fused with the minor coat protein, gIIIp, of M13 bacteriophage for surface display. The Western blot analysis revealed that using the phage based vector, M13CD41923, all the copies of gIIIP (3-5 per virion) were present as fusion protein indicating multivalent display. In the phagemid based vector, phage particles were produced only upon infection of the cells carrying pVCCD43426, with the helper phage, M13KO7. Thus these phage particles carried both, the fusion protein as well as the unfused gIIIp, as shown by Western blot analysis. The presence of large amount of unfused gIIIp ensured that the phage particles did not display more than one fusion protein per phage particle, thus leading to monovalent display. Phage particles produced by both vectors could be captured on immobilized gp120, thereby showing that the displayed CD4 domains were functional. PMID- 8002013 TI - Uncoupling of photosystems during light dependent dinitrogen fixation by a non heterocystous cyanobacterium Plectonema boryanum. AB - Plectonema boryanum grows under microaerobic nitrogen starvation conditions by temporal separation of the oxygen-sensitive nitrogen fixation and the oxygen evolving photosynthesis. During the nitrogen-fixation phase, depression in light dependent oxygen evolution results from alterations in the stare of QA/QB complex. The reaction centre in photosystem II is not oxidised efficiently. Light dependence of nitrogenase function under such conditions appears to be related to the coupling of photosystem I to endogenous electron donors, such as glycollate. This cyanobacterium provides a natural example of in vivo shift in coupling between the photosystems during nitrogen-fixing growth. PMID- 8002014 TI - Interaction of guanidine hydrochloride and guanidine thiocyanate with wheat germ lipase. AB - Effect of two classical and potent denaturants, guanidine hydrochloride (GuHCl) and guanidine thiocyanate (GuHSCN) on purified wheat germ lipase has been studied. Lipase was found to be active only up to 5 M GuHCl and 1.5 M GuHSCN. The extent of interaction was determined by the measurement of apparent partial specific volume of the enzyme in presence of these two denaturants. While the preferential interaction parameter (zeta 3) has values of 0.08 +/- 0.02 and 0.14 +/- 0.03 g/g, the interaction parameter (delta m3/delta m2)T,mu 1, mu3 has values of 35 +/- 9 and 50 +/- 10 mole/mole for GuHCl and GuHSCN, respectively. The number of denaturant molecules bound to the enzyme, A3, obtained experimentally were 0.486 +/- 0.020 and 0.348 +/- 0.020 g/g and the calculated values were 0.459 +/- 0.023 and 0.567 +/- 0.030 g/g for 6 M GuHCl and 3 M GuHSCN, respectively. The volume change occurring upon denaturation results in -420 +/- 42 and -462 +/- 84 ml/mole in 6 M GuHCl and 3 M GuHSCN, respectively. The denaturation is accompanied by exposure of hydrophobic groups to the bulk solvent as confirmed by fluorescence emission measurements of the enzyme. The Tm measurements indicated a control value of 56 +/- 1 degree C. In presence of 6 M GuHCl/3 M GuHSCN, the value was 42 +/- 1 degree C. These results explain the retention of lipase activity even at 5 M GuHCl from a mechanistic point of view. PMID- 8002016 TI - cDNA clones for salt-inducible genes from mustard (Brassica juncea). AB - Treatment of a salt tolerant variety of mustard (Brassica juncea cv RH30), with 0.2M NaCl for 96 hr was found to induce synthesis of three new polypeptides and accumulation of proline. A cDNA library from mRNAs derived from salt stressed plants was constructed in the expression vector lambda gt11. Screening by differential hybridization and by salt stress specific antibodies gave two clones msc1 and msc2 (mustard salt clone) respectively. msc1 hybridized to transcripts from salt stressed mustard seedlings only after 48 hr of 0.2M NaCl stress as also to transcripts from drought stress induced by 10% PEG for 24 hr. msc 1 cross hybridized with msc2 clone. The results show the common mechanism of stress response as elicited in other plants. PMID- 8002015 TI - Primary structure of sesbania mosaic virus coat protein: its implications to the assembly and architecture of the virus. AB - Sesbania mosaic virus (SMV) is a plant virus that infects Sesbania grandiflora plants in Andhra Pradesh, India. The amino acid sequence of the coat protein of SMV was determined using purified peptides generated by cleavage with trypsin, chymotrypsin, V8 protease and clostripain. The 230 residues so far determined were compared to the corresponding residues of southern bean mosaic virus (SBMV), the type member of sobemoviruses. The overall identity between the sequences is 61.7%. The amino terminal 64 residues, which constitute an independent domain (R domain) known to interact with RNA, are conserved to a lower extent (52.5%). Comparison of the positively charged residues in this domain suggests that the RNA-protein interactions are considerably weaker in SMV. The residues that constitute the major domain of the coat protein, the surface domain (S-domain, residues 65-260), are better conserved (66.5%). The positively charged residues of this domain that face the nucleic acid are well conserved. The longest conserved stretch of residues (131- 142) corresponds to the loop involved in intersubunit interactions between subunits related by the quasi 3-fold symmetry. A unique cation binding site located on the quasi 3-fold axis contributes to the stability of SMV. These differences are reflected in the increased stability of the SMV coat protein and its ability to be reconstituted with RNA at pH 7.5. A major epitope was identified using monoclonal antibodies to SMV in the segment 201-223 which contains an exposed helix in the capsid structure.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8002017 TI - Testis-specific histone (H1t) is not phosphorylated and has a weak interaction with chromatin. AB - Soluble chromatin was prepared from rat testes after a brief micrococcal nuclease digestion. After adsorption onto hydroxylapatite at low ionic strength, the histone H1 subtypes were eluted with a shallow salt gradient of 0.3 M NaCl to 0.7 M NaCl. Histone H1t was eluted at 0.4 M NaCl, while histones H1a and H1c were eluted at 0.43 M NaCl and 0.45 M respectively. The extreme divergence of the amino acid sequence of the C-terminal half of histone H1t, the major DNA binding domain of histone H1, from that of the somatic consensus sequence may contribute to the weaker interaction of histone H1t with the rat testis chromatin. Further, histone H1t was not phosphorylated in vivo in contrast to histone H1a and H1c, as is evident from the observation that histone H1t lacks the SPKK motif recognized by the CDC-2kinase or the RR/KXS motif recognized by protein kinase A. PMID- 8002018 TI - DNA topoisomerase I from Mycobacterium smegmatis. AB - DNA topoisomerase I has been purified from Mycobacterium smegmatis to near homogeneity using different column chromatographic techniques. The enzyme activity relaxes form I DNA into form IV DNA, requiring Mg2+, but not ATP or any other cofactors for its activity. Several properties of the enzyme were found to be similar to that of the prototype enzyme, Escherichia coli topoisomerase I. PMID- 8002019 TI - Differential domain folding/unfolding of gamma-crystallins: existence of two distinct groups. AB - High resolution calorimetry and spectral measurements have been employed to examine folding/unfolding behaviour of gamma-crystallins which are known to contain two homologous domains. Results have been analyzed in terms of selective unfolding of domains, interdomain interactions, conformational stability and the existence of intermediates in the order-disorder transition equilibrium. Both spectral and thermotropic data indicate that, in terms of structural hierarchy, these proteins can be divided into two distinct groups, gamma II and gamma IIIB belonging to one and gamma IIIA and gamma IVA to the other. The unfolding/folding characteristics of these two groups are distinctly different. Equilibrium unfolding of gamma II and gamma IIIB is biphasic indicating the existence of an intermediate in which one domain unfolds and the other remains in the native form. The absence of a cooperative transition in gamma IIIA and gamma IVA in acidic urea has also been attributed to a structured intermediate, most likely a molten globule, which may not be thermodynamically as distinct as of the former group. The difference in the equilibrium folding/unfolding transition of these two groups has been explained by subtle differences in the packing arrangement of their two domains and interactions between them. Since the intermediates, under certain circumstances, are known to aggregate, they are likely to play a critical role in the etiology of human cataract formation. PMID- 8002020 TI - Investigations into size heterogeneity of the alpha B-crystallin mRNA. AB - alpha B-crystallin is expressed in a variety of developmental, physiological and pathological conditions in a number of tissues. Based on northern blots of total RNA, the existence of at least two size classes of alpha B-crystallin mRNAs has been reported, one smaller predominant species, 0.8-0.9 kb, and the other 1.2 to 1.4 kb. This heterogeneity has been attributed to alternative upstream transcriptional initiation. We have investigated the origin of the size heterogeneity of alpha B-crystallin mRNA by using 5'-upstream-, coding- and 3' untranslated-region probes in RNAse protection and northern blot assays. RNAse protection assays indicate that there is only one predominant initiation site as previously reported and that the second polyadenylation signal is not used in the rat gene. Importantly, northern blot data obtained with coding region-only probe shows that the size of alpha B mRNA detected in the heart and the lens is similar (0.78 kb) in poly A+ as well as in total RNA. On the other hand, in the brain and in the lung, the larger hybridizing species (1.05 kb and 1.22 kb respectively) seen in total RNA are not detected in poly A+RNA which shows a 0.95 kb species in both tissues. The 5' upstream probe (-1 to -499) produces weak hybridization patterns in the brain and the lung, similar to those obtained with coding region only probe. The 5' probe did not show hybridization in the heart and the lens RNAs. These data suggest that upstream initiations represent a minor population of transcripts and that higher size transcripts (about 500 bp larger) actually represent non-polyadenylated RNAs that may not contribute to the generation of the actual gene product. PMID- 8002021 TI - An unusual distribution of glucose-6-phosphate dehydrogenase deficiency of south Indian newborn population. AB - Glucose-6-phosphate dehydrogenase (G6PD) deficiency is seen at a higher frequency in many national and ethnic groups in areas of current or former malaria endemicity. A screening programme undertaken to evaluate the gene frequencies for this deficiency in the highly inbred South Indian population of Karnataka revealed that of the 5140 neonates screened, 7.8% were G6PD deficient with no correlation between the reported level of inbreeding and enzyme deficiency. An interesting finding was the equal number of male (198) and female (207) individuals, with G6PD activity of less than 3 IU. The possible implications of this finding with regard to the expression of G6PD gene is discussed. PMID- 8002022 TI - Characterization of a variant glucose-6-phosphate dehydrogenase from the south Indian population. AB - Glucose-6-phosphate dehydrogenase (G6PD) is coded by a gene on the X-chromosome. Earlier studies have shown that the South Indian population has a high incidence of this enzyme deficiency. The electrophoretic mobility, pH optimum and the Km values for G6PD from normal and variant individuals were identical. However, the specific activity of the variant enzyme was 8 times less compared to the value of the normal enzyme. Western blot analysis of partially purified G6PD from normal and variant individuals performed using equal amounts of total protein showed that the variant protein was 3 times less in concentration. Similar analysis performed using protein corresponding to equal enzyme activity units in the normal and variant samples showed that the variant enzyme was 2.25 times less efficient compared to the normal enzyme. RNA dot blot analysis using full length G6PD cDNA probe (PGDT5B, a kind gift from Prof. L Luzzatto) revealed that lymphocytes from normal and variant individuals had equal amounts of G6PD specific mRNA. PMID- 8002023 TI - Human T-cell responses to blood stage antigens in Plasmodium falciparum malaria. AB - Immunity to malaria involves both cell-mediated and humoral immune mechanisms. T cells are essential both in regulating antibody formation and in inducing antibody-independent immunity. Thus, acquisition and maintenance of protective immunity to malaria is T-cell dependent. Although relatively neglected until recently basic knowledge of T-cell subsets and cytokine production determining the course of a malaria infection is advancing rapidly at present. In this paper we will review recent findings contributing to the understanding of immune mechanisms against the asexual blood stages of human P. falciparum malaria. PMID- 8002024 TI - Effector mechanisms against asexual erythrocytic stages of Plasmodium. AB - Evidence for a role for macrophages/monocytes is largely based on in vitro not in vivo observations. Products of activated macrophages particularly tumor necrosis factor-alpha (TNF alpha) are implicated in the killing of parasites. Access of cytokines and other factors might be through intracellular channels in the infected red blood cell. The cytotoxic elements in 'crisis' serum are uncertain but may include TNF, gamma-interferon (IFN gamma), and lipid peroxidases. TNF alpha in excess, contributes to pathology. TNF, acting as a pyrogen and raising body temperature, may moderate parasite density by killing late asexual stages. Nitric oxide and other nitrogen intermediates, products of activated macrophages and a number of other cell types, have been demonstrated both in vitro and in vivo to have a protective role. Phagocytosis of infected erythrocytes and merozoites, enhanced by the presence of immune serum in some systems, has been reported. Killing of parasites by neutrophils is enhanced by immune serum and cytokines TNF alpha, IFN gamma and lymphotoxin. A role for natural killer cells has been suggested. Evidence for antibody-dependent cellular cytotoxicity (ADCC) is controversial. Antibody-dependent cellular inhibitory activity (ADCI) (blood monocytes plus immune IgG) has been described for P. falciparum. Evidence for an important role for complement is conflicting; an involvement in the protective activity of phagocytic cells is reported. Antibody isotypes have been relatively little studied. In murine systems IgG2a may have a role early in the protective immune response followed by IgG1. In P. falciparum ADCI activity is mediated by IgG1 and IgG3, two cytophilic isotypes.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8002025 TI - Mechanisms of defense against P. falciparum asexual blood stages in humans. AB - Based on the observation that host-parasite immune relationships depend not only on the parasite species but also on the host, we consider that P. falciparum can be best studied in humans. In vivo observations suggest that there are in humans a series of immunities towards P. falciparum: besides innate non-antigen-specific defenses, which play a major role, additional defense mechanisms are acquired after consecutive malaria attacks. They contribute to realize such various states of immunity as acquired resistance to cerebral malaria, anti-disease immunity, strain-specific immunity, and, after a long time of exposure in hyper- or holoendemic areas, the host-parasite equilibrium characteristic of premunition. Passive transfer experiments have established that IgG play a major role in premunition. We review, on the one hand, in vitro evidences that protective antibodies have the characteristic capacity of promoting a monocyte-dependent inhibition of parasite growth (ADCI) and, on the other hand, the in vivo observations that suggest that this mechanism of defense could be one of the immune foundations of the state of premunition. PMID- 8002026 TI - Human T-cell repertoire, heterogeneity and memory: relevance to malaria. AB - There is abundant evidence that most non-exposed donors have cells able to respond to malaria antigens. These cells have the properties of memory T cells and probably arise as a result of cross-reactive priming by other microbial antigens. The existence of a high frequency of cross-reactive primed cells would be predicted to bias the response to malaria antigens, both in terms of specificity and the type of effector cells generated. It is possible that this bias may interfere with the development of effective anti-malaria responses. PMID- 8002027 TI - Immunological responses from non-exposed donors to malaria antigens: implications for immunity and pathology. AB - An approach to identification of epitopes suitable for vaccine development has been to locate regions of malaria target antigens that are recognized by individuals with clinical immunity. This has applied to identification of T- and B-cell epitopes. It is now realized, however, that T cells from individuals without prior exposure to malaria can respond to malaria parasites, malaria proteins, and peptides copying protein sequences. Such observations raise questions about which epitopes we should be targeting for vaccine development, but also challenge our understanding of immunological memory. Such responses from non-exposed individuals may also be important in expression of disease symptoms. PMID- 8002029 TI - Four epitopes on tumor necrosis factor-alpha defined by murine anti-tumor necrosis factor-alpha monoclonal antibodies. AB - Eight murine anti-TNF alpha monoclonal antibodies (mAb) were produced after immunization of BALB/c mice with rhTNF alpha. Six of these mAbs were able to neutralize cytotoxic activity of TNF alpha against L929 cells. Two other mAbs had no neutralizing effect. Epitope mapping studies were performed by ELISA and by using a BIAcore system (Pharmacia). The described mAbs were allowed to define 4 different epitopes on TNF alpha. Three of them were involved in the binding of TNF alpha with its receptor (cytotoxic neutralization of TNF alpha). Another epitope was defined by non-neutralizing mAbs. PMID- 8002028 TI - Binding of anti-DNA antibodies to oxidatively damaged DNA in spouses and relatives of patients with systemic lupus erythematosus. AB - The prevalence of serum anti-DNA antibodies was evaluated by ELISA using oxidatively damaged DNA as antigen in 21 patients with systemic lupus erythematosus (SLE), in 9 spouses and in 15 first-degree relatives. These were compared with 12 healthy controls. There was no significant difference in the levels of serum antibodies detected between the group of spouses and normal controls with all results within the normal range of the assay. Binding of serum antibodies to the oxidatively damaged DNA was detectable in 12 (80%) of the relatives studied, and the range of values obtained overlapped significantly with the SLE patient group. The relevance of these antibodies to the immunopathology of SLE is unclear since they appear to be present in the absence of any clinical symptoms. However, they may be useful predictively as a marker for those individuals who are more likely to develop SLE. PMID- 8002031 TI - Detection of adult T-cell leukemia-derived factor/human thioredoxin in human serum. AB - Adult T-cell leukemia (ATL)-derived factor (ADF), originally defined as an inducer of interleukin-2 receptor/alpha-chain (IL-2R/p55) of human T-lymphotropic virus type I (HTLV-I) positive T cells, is a human homologue of redox-active coenzyme thioredoxin (Trx) of Escherichia coli. In this study, an enzymatic assay system based on the dithiol-dependent insulin-reducing activity of ADF/Trx was established (insulin-reducing assay) to determine the amount of ADF/Trx in human serum using NADPH and Trx reductase purified from human placenta. Insulin reducing activity was detected in all of the serum samples from healthy volunteers (n = 30) screened by this assay, with a mean +/- SD of 10.9 +/- 2.4 U/l. This mean value corresponds with the concentration of 223 ng recombinant ADF/Trx (rADF/Trx)/ml. Human serum is known to contain several redox-active proteins with ADF/Trx motifs. To differentiate the contribution of these proteins and ADF/Trx to the insulin-reducing activity, the anti-rADF/Trx monoclonal antibody (mAb)-conjugated affinity column-depleted sera obtained from an identical source was used for analysis. The affinity column-depleted sera demonstrated a loss of over 99% of the original activity, while control column depleted sera lost less than 4%. Furthermore, the amount of affinity-purified ADF/Trx molecules eluted from the same column almost corresponded with the amount estimated by the insulin-reducing activity.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8002030 TI - Autoreactivity in HIV-infected individuals does not increase during vaccination with envelope rgp160. AB - The HIV-1 envelope protein contains several regions with amino acid homology to HLA class I and class II molecules. We evaluated possible changes in antibody responses to those regions during vaccination with rgp 160 produced in a baculovirus system. Forty asymptomatic HIV-infected patients with CD4 cell counts above 400 were vaccinated with rgp 160. Twenty-one patients were tissue-typed as HLA A2. Sixty-two percent of these patients exhibited cytotoxic lymphocyte antibodies directed to CD8+, HLA A2 cells. This cytotoxicity decreased during HIV gp160 vaccination. In order to further characterize the specificity of these responses, analogues of HLA class I and HLA-DR peptides were chemically synthesized together with their correct HIV-1 gp160 sequences. Enzyme-linked immunosorbent assays (ELISA) with sera from before, during and after immunization were performed with HIV proteins, peptides and their homologues. All patients showed an increase in their previously poor specific T-cell activation to gp160. Fourteen patients developed increased avidities or titres to HIV proteins and/or peptides. Contrarily, serum IgG titers to the HLA homologous peptides were initially low and decreased further during the course of vaccination. This decrease occurred in the majority of patients, 35-40 of the 40 individuals, depending on the antigen. Independent measures of autoantibodies to Ro/SS-A and La/SS-B remained undetectable. PMID- 8002032 TI - Antibodies against CD4+ lymphocytes in plasma of HIV-infected patients are related to CD4 cell depletion in vivo. AB - The role of autoimmune phenomena in the pathogenesis of AIDS is not well understood. Antibodies against CD4+ lymphocytes are frequently detectable in HIV infected patients. However, the relevance of these antibodies is unknown. In this study anti-CD4 cell antibodies in plasma of HIV-infected patients were compared to patients' CD4 cell count. Lymphocytes of a healthy donor were incubated with plasma of patients and controls. Antibodies against CD4+ lymphocytes were detected using anti-human Ig antibodies and monoclonal anti-CD4 antibodies simultaneously. The degree of staining was visualized by flow cytometry. The experiments revealed that 60% of HIV-infected patients harbored anti-CD4 cell antibodies in their plasma. Anti-CD4 cell antibodies were not detectable in plasma of healthy controls. Patients with anti-CD4 cell antibodies in their plasma presented with significantly lower numbers of circulating CD4+ lymphocytes (P = 0.025). The degree of antibody reactivity was negatively correlated to patients' CD4 cell counts (P = 0.02). In conclusion there is evidence for an association between plasma anti-CD4 cell antibodies and CD4 cell depletion. Whether this association represents an epiphenomenon or a pathogenetic relevant pathway needs to be investigated in further studies. PMID- 8002033 TI - Lysis of allogeneic and syngeneic target cells by primary cytotoxic T lymphocytes induced in vitro by Drosophila melanogaster cells. AB - Incubation of unprimed splenocytes directly with synthetic peptides induces CD8+ primary CTL in vitro. The ability of peptide-pretreated LPS blasts or H-2Db expressing Drosophila melanogaster cells to induce peptide-reactive primary CTL was analysed using synthetic peptides corresponding to distinct and overlapping amino acids in SV40 T antigen Db-restricted T-cell epitopes I, II-III, and V. Peptide-pretreated, but not untreated, LPS blasts induced strong peptide-reactive CTL in splenocytes of naive C57 BL/6 mice. The reactivity of these CTL was indistinguishable from that of CTL induced by direct stimulation of spleen cells with peptides. In contrast, effector cells induced by untreated or peptide pretreated drosophila cells expressed equivalent cytolysis both against untreated and peptide-pretreated syngeneic target cells. They also strongly lysed the allogeneic (H-2d) P815 target cells. The cytolytic activity was expressed by CD8+ T lymphocytes. However, the lack of specificity and restriction was probably due to stimulation of LAK cells as well. The CTL-inducing potential of the drosophila cells was stable at 46 degrees C. Peptide-activated splenocytes cultured for 1 month in medium supplemented with spent medium from drosophila growth culture were 75% B cells and 25% CD4+ T cells. Taken together, these results indicated that LPS blasts are efficient APC for induction of primary CTL and that drosophila cell-derived molecule(s) are capable of inducing broad-reactive effector cells and may also assume the function of leukocyte growth factor(s). PMID- 8002035 TI - Intestinal intra-epithelial lymphocytes in LEC mutant rats. AB - LEC rat is a novel strain showing a maturational arrest from CD4+8+ to CD4+8- cells but not to CD4-8+ cells in the thymus. In this study, we examined if this mutation affects the differentiation of intestinal intra-epithelial lymphocytes (IEL) in LEC rats. In normal rat IEL, all 4 subsets with respect to the CD4/CD8 expression were observed. The CD4-8+ population was dominant and a unique population, CD4+8+, was observed as already shown in previous papers. Both CD4+8- and CD4+8+ cells were CD3+, TCR-alpha/beta +, CD45RC-, and CD5+, whereas CD4-8+ cells consisted of a heterogeneous population, being CD3+, TCR-alpha/beta +/-, CD45RC+/-, and CD5-. In LEC rat IEL, CD4+8- and CD4+8+ cells existed normally and distribution of CD4/CD8 subsets was not different from that of normal rat IEL. Furthermore, the expression pattern of CD3, TCR-alpha/beta, CD45RC and CD5 was not different from that of normal rat IEL in each subset. These results suggest that maturational arrest of CD4+8- thymocytes does not affect IEL maturation, especially maturation of CD4+8- IEL, suggesting that the IEL maturation mechanism for CD4+8- cells is independent of that of thymocytes. PMID- 8002034 TI - Functional analysis of T-cell antigen 4-1BB in activated intestinal intra epithelial T lymphocytes. AB - The 4-1BB antigen has been recently demonstrated to be a 30 kDa inducible T-cell antigen and is expressed on the cell surface of activated splenic T cells and thymocytes. This novel T-cell antigen also associates physically with the T cell specific protein tyrosine kinase, p56lck. We show here that the inducible T-cell antigen 4-1BB is expressed on activated intestinal intra-epithelial T lymphocytes (IEL). After activation, or in the presence of IL-2, the activated IELs showed higher levels of 4-1BB. Functional studies revealed that the activated IELs triggered with anti-4-1BB monoclonal antibody could enhance the level of IEL cytotoxicity against anti-CD3-secreting hybridoma cells. Cross-linking of anti-4 1BB antibody also enhanced the proliferation of IELs. These results suggest that the inducible antigen 4-1BB has broad biological functions which not only play a role in activated splenic T cells and thymocytes but also in the mucosal immune system. PMID- 8002036 TI - Release of alpha-melanocyte-stimulating hormone from rat splenocytes in vitro is dependent on protein synthesis. AB - The pro-opiomelanocortin (POMC) peptide product alpha-melanocyte-stimulating hormone (alpha-MSH) has a variety of anti-inflammatory effects within the immune system. Using an antiserum specific for alpha-MSH, we have now demonstrated for the first time that this peptide is secreted from splenocytes. Basal secretion of alpha-MSH from the spleen in vitro was some 300-fold less than that detected from the neurointermediate lobe. Secretion of alpha-MSH from the spleen was increased 5-fold in the presence of puromycin, indicating that splenocyte alpha-MSH secretion is under the regulation of a product of endogenous protein synthesis. ACTH and beta-endorphin were also released from splenocytes in vitro, but their release was not affected by incubation with puromycin. Secretion of the POMC peptides from splenocytes or NIL was not affected by corticosterone. These data show that the many anti-inflammatory effects within the immune system ascribed to alpha-MSH may actually be mediated through paracrine effects of immune alpha-MSH. PMID- 8002037 TI - T-cell recognition of an allogeneic RT1-Dbu class II MHC peptide. AB - The allo-antibody response of several rat strains to an unconjugated synthetic 20 amino acid peptide derived from the alpha helical region of the RT1-Du beta chain was tested. The LEW (RT1l) and WAG (RT1u) strains produced little or no antibody; the PVG (RT1c) and DA (RT1av1) strains produced moderate amounts of antibody; while the BN (RT1n) strain produced strong primary and secondary antibody responses. This suggested that the BN strain was able to process and present the RT1-Dbu peptide on its class II molecules. In vitro proliferation studies demonstrated that LEW T cells did not respond to the peptide, whereas BN T cells responded strongly, and that the response in the BN strain was found only in the CD4+ T-cell subset. However, immunisation of BN rats with the RT1-Dbu peptide failed to cause any acceleration of rejection of WAG skin or kidney grafts. Moreover, BN rats primed with WAG skin and kidney grafts did not produce T cells reactive to the RT1-Dbu synthetic peptide. This suggests that the T-cell response of the BN strain to the synthetic major histocompatibility complex peptide was not relevant to the indirect T-cell allo-recognition response to naturally processed RT1-Du beta chains. PMID- 8002038 TI - HLA-DQ and TAP2 genes in patients with insulin-dependent diabetes mellitus. AB - We examined the prevalence of HLA-DRB1, DQB1, DQA1 and TAP2 genes in children with insulin-dependent diabetes mellitus (type 1 diabetes). These HLA and TAP2 alleles were identified by dot-blot analysis of polymerase chain reaction (PCR) amplified genomic DNA with sequence-specific oligonucleotide probes. The results show that those DQB1 alleles, which carry non-aspartic acid at position 57, in conjunction with DQA1 alleles carrying arginine at position 52, are strongly associated with susceptibility to type 1 diabetes. The prevalence of the TAP2* 0201 allele in diabetic patients was significantly lower than that in normal controls. Analysis of the data suggests that DQ alleles have the primary association with type 1 diabetes and that the association of TAP2 alleles with the disease is secondary. PMID- 8002039 TI - A new visual enzyme immunoassay of methamphetamine using linear water-soluble polyelectrolytes. AB - A new visual enzyme immunoassay (EIA) technique has been developed. Oppositely charged synthetic linear water-soluble polyelectrolytes (poly-N-ethyl-4-vinyl pyridine as polycation and polymethacrylate as polyanion) were used as carriers for reagent immobilization. The ability of these molecules to form an insoluble complex was applied for the separation of bound and free components of the immunoassay reaction mixture. This approach was realized in methamphetamine visual EIA. In the first stage of the assay two specific reactions took place during incubation of the analytical reagents with the probe to be analyzed: (1) competition between methamphetamine and hapten conjugated with peroxidase for the interaction with specific antibodies and (2) interaction of these antibodies with the protein A-polymethacrylate conjugate. As a result of these reactions the (polyanion-protein A)-antibody-(hapten-peroxidase) complex was formed. Then the reaction mixture was filtered through an Ultrabind membrane (0.45 microns) with adsorbed poly-N-ethyl-4-vinylpyridine, and the immunological complexes were immobilized to the membrane by electrostatic interaction. The level of peroxidase binding on the membrane was measured by diaminobenzidine substrate. The system described was optimized to achieve both high rapidity (20 min) and an appropriate sensitivity (0.4 micrograms/ml) for methamphetamine assay. PMID- 8002040 TI - Cyclophilin A and an antibody against cyclosporin A resemble each other in their binding sites. AB - The three-dimensional structures of cyclosporin A complexed with cyclophilin A or Fab fragment of a monoclonal antibody were compared. In these two complexes conformations of the fragment D-alanine8-N-methylvaline11 in cyclosporin A were in a good agreement. In addition, cyclophilin A and the Fab fragment had related arrangements of the aromatic amino acids in their binding sites, implying that antibody independently utilizes similar structural themes for binding cyclosporin A as cyclophilin A. PMID- 8002041 TI - Immunization of mice with Escherichia coli containing an antigen of the malaria parasite Plasmodium chabaudi chabaudi expressed in lambda gt11 induces high antibody titres. AB - Escherichia coli containing a recombinant malarial protein expressed in lambda gt11 have been evaluated as an antigen delivery system in vivo. They were generated by infecting non-suppressing E. coli cells with a clone from a cDNA library of Plasmodium chabaudi chabaudi in lambda gt11. This clone (termed clone 6) expresses part of a 93 kDa blood-stage antigen of P. c. chabaudi as beta galactosidase fusion protein. Immunization of C57B1/6 mice with these infected E. coli cells resulted in an antibody response to the malarial part of the fusion protein comparable to that obtained with purified fusion protein preparations. This method, therefore represents a rapid secondary screening of clones from lambda gt11 expression libraries for immunogenic and potentially protective components. In addition, the administration of whole infected E. coli obviates the need for an adjuvant. PMID- 8002042 TI - Priming of the anterior pituitary with corticotropin-releasing hormone in vitro does not facilitate an ACTH response to interleukin-1 beta. AB - Stimulation of the hypothalamo-pituitary-adrenal axis by the cytokine interleukin 1 beta (IL-1 beta) is an important facet of the functional interaction between the endocrine and immune systems. IL-1 beta can act by releasing corticotropin releasing hormone (CRH) from the hypothalamus, but it has also been proposed to act directly at the anterior pituitary when the pituitary has been primed with CRH. We tested this hypothesis using in vitro experiments in which anterior pituitaries were primed with low doses of CRH. We were unable to demonstrate a direct effect of IL-1 beta on the release of ACTH from freshly harvested anterior pituitary tissue. Neither continuous nor discontinuous priming of the cells with CRH or arginine vasopressin, at concentrations by themselves insufficient to cause ACTH release, facilitated an ACTH response to IL-1 beta. Therefore our data do not support the hypothesis that IL-1 beta can have a direct effect upon ACTH release from the anterior pituitary primed with CRH. PMID- 8002043 TI - Tumor necrosis factor alpha and soluble tumor necrosis factor receptors in individuals with human immunodeficiency virus infection. AB - There is some ongoing debate as to whether tumor necrosis factor (TNF) alpha levels are elevated in human immunodeficiency virus infection (HIV), however TNF alpha is rapidly cleared from the circulation and long-term markers have to be analyzed. Two distinct TNF alpha receptors have been identified, which also exist in soluble forms. The aim of this study was to investigate whether an association in HIV infection exists between the serum levels of TNF alpha, the two soluble TNF receptors (sTNFRs) and other soluble immune activation markers, namely neopterin and beta 2-microglobulin, and the number of CD4+ T-cells. We investigated 63 individuals with HIV infection for serum levels of TNF alpha, sTNFR 55, sTNFR 75, beta 2-microglobulin and urinary neopterin. The study population comprised all stages of HIV infection: 35 were asymptomatic, 8 had oral candidiasis, 4 had constitutional signs and 16 had AIDS. Circulating levels of TNF alpha were detectable in 22 of 63 (34.9%) individuals. For those with detectable TNF alpha levels the median concentration was 40 pg/ml. The frequency and extent of TNF alpha levels found in those with advanced HIV infection as defined by a CD4+ T-cell count below 320 x 10(6)/l did not differ significantly compared to those with a higher CD4+ T-cell count. Increased concentrations were found in 69.8% of the patients for sTNFR 55 and in 87.3% for sTNFR 75. Serum concentrations of sTNFR 55 and sTNFR 75 were higher in the group with the lower CD4 T-cell count (P = 0.006 and P = 0.0003). TNF alpha correlated with sTNFR 75 and weakly with sTNFR 55 and beta 2-microglobulin.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8002045 TI - Inhibition of natural killer cell activity by dietary lipids. AB - Natural killer (NK) cells are a subset of cytotoxic lymphocytes found mainly in blood and the spleen. NK cells play a role in natural immunity to microbes, viruses and tumor cells and are involved in the rejection of grafts. The present study investigated the effects of diets containing oils rich in saturated fatty acids, mono-unsaturated fatty acids, n-6-poly-unsaturated fatty acids (PUFA) or n 3-PUFA on the NK cell activity and on the lymphokine-activated killer (LAK) cell activity of rat spleen lymphocytes. Weanling rats were fed for 10 weeks on a low fat (LF) diet (approximately 2% fat by weight) or on 1 of 5 high-fat (HF) diets, which contained 20% (by weight) hydrogenated coconut oil (HCO), olive oil (OO), safflower oil (SO), evening primrose oil (EPO) or menhaden (fish) oil (MO). Each of the HF diets suppressed the NK activity of freshly prepared spleen lymphocytes compared with the LF diet; cells from the MO-fed rats exhibited the lowest NK activity. Culture with IFN alpha for 3 h increased the NK activity of spleen lymphocytes from all animals, except those fed the OO diet; the increase in NK activity varied from 20% (LF) to 50% (MO). Although feeding the OO, EPO or MO diets resulted in lower IFN alpha-stimulated NK activity than that obtained by feeding the LF diet, the only consistent significant difference was the lower activity of the cells from the OO-fed rats compared with those from the LF-fed rats.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8002044 TI - Group-selective immunoassay. AB - A new solid-phase immunoassay technique has been applied for anti-digoxin monoclonal antibodies (Mabs) detection. At the first assay step, anti-digoxin Mabs (IgG1, Kaff = 9.2 x 10(9) M-1) were bound to a specially prepared immunosorbent, the microtiter plates coated with digoxin-human serum albumin conjugate (Dig-HSA), in which free amino groups were protected by a glutaraldehyde cross-linking modification. The modification did not essentially influence the antibody-binding capacity of the immunosorbent. After antigen antibody reaction, free amino groups were located only on the anti-digoxin Mabs, bound to chemically modified immunosorbent. At the second assay step, free amino groups of anti-digoxin Mabs were biotinylated by N-hydroxysuccinimide-biotin ester. Then the biotin residues were detected by the streptavidin-peroxidase conjugate. The method does not require second labeled antibodies and may be used for anti-hapten hybridoma screening. PMID- 8002046 TI - Development of an ELISA assay for soluble CD35 (C3b/C4b receptor): high levels of soluble CD35 in LE-positive patients with hematological malignancies. AB - Malignant cells usually lack CD35 (complement receptor type 1, C3b/C4b receptor), a differentiation surface antigen. We measured soluble forms of CD35 in the plasma of normal subjects and patients with various malignant diseases. A microassay for the determination of CD35 was established based on a sandwich enzyme immunoassay using 2 monoclonal antibodies that recognize different epitopes. Soluble CD35 was not detected in any plasma samples from normal subjects or from patients with a variety of solid cancers: i.e., levels were below 20 ng/ml. On the other hand, 3 of 70 patients with hematological malignancies showed high levels of plasma CD35. The molecular mass of the soluble form was about 200 kDa, which is similar in size to membrane forms of CD35. Although the clinical conditions differed in these patients, they had high transaminase titers and detectable autoantibody. Complement titers (CH50) and the levels of membrane complement regulatory proteins were within the normal range in these patients. Although the mechanism by which it is produced remains unknown, soluble CD35 is present in significant amounts in association with immunological disorders secondary to hematological malignancies. PMID- 8002047 TI - Interactions between cytokines and eicosanoids: a study using human peritoneal macrophages. AB - To examine the interactions between the main pro-inflammatory cytokines and eicosanoids produced by human inflammatory cells, human peritoneal macrophages (hp-M phi) were isolated from ascitic fluid of patients with portal hypertension. Interactions between interleukin-1 beta (IL-1 beta), IL-6, tumor necrosis factor alpha (TNF-alpha), leukotriene B4 (LTB4) and prostaglandin E2 (PGE2) were studied by addition or inhibition of several cytokines and eicosanoids: human recombinant IL-1 beta (hrIL-1 beta) addition, LTB4 addition and 5-lipoxygenase inhibition (6 hydroxy-2-(4-sulfamoylbenzylamino)-4,5,7-trimethylbenzothiaz ole hydrochloride (E6080)), PGE2 addition and cyclooxygenase inhibition (indomethacin). In hp-M phi hrIL-1 beta stimulated the LTB4 production, while the PGE2 production was inhibited. HrIL-1 beta had no significant effect on IL-6 production in hp-M phi. LTB4 did not regulate IL-1 beta and IL-6 production. Increasing PGE2 down regulated the TNF-alpha production, but did not effect the IL-1 beta and IL-6 production. PMID- 8002048 TI - Characterization of a B-CLL derived IgM-lambda antibody expressing typical features of a NPAB. AB - A human IgM-lambda hybridoma (CB-HB) was established from chronic lymphocytic leukaemia (CLL) B-cells. Immunochemical and molecular characterization of the monoclonal antibody (mab) produced by the CB-HB cells offered typical features of natural polyreactive antibodies (NPAPs) found in fetal and healthy adult organisms. In particular, the CB-HB mab reacted with different self and foreign (viral and bacterial) antigens when tested in three independent systems (solid- and fluid-phase ELISA, Western blot) showing binding constants in a range from 1.9 x 10(-7) to 7.5 x 10(-8) mol/l to four antigens chosen. In addition, the CB HB mab binding could be inhibited by a rabbit polyclonal antiserum specific for a common idiotype (Id 102) on human polyreactive (auto)antibodies. The variable region of the CB-HB mab was found to be encoded by unmutated copies of germline genes. Interestingly, the VH-DP10 (51p1) segment, encoding for the autoantibody associated G6-cross reactive idiotype frequently expressed on both fetal and malignant B-cells, was found to be used with a V segment (VLO11). Collectively these data imply that cells belonging to the natural polyreactive B-cell repertoire undergo malignant transformation. A stimulation by autoantigens or common foreign antigens may be involved. PMID- 8002050 TI - Antigen processing in earthworms. AB - The administration of protein antigens into earthworms Lumbricus terrestris and Eisenia foetida induces the formation of antigen-binding protein (ABP) with the maximum response occurring between days 4 and 8. High proteolytic activities observed both in coelomocytes and in coelomic fluids cause rapid antigen degradation; the majority of antigen is digested during the first 24 h. To analyze the role of proteolytic processing of antigen in ABP response in vitro, the intact antigen (ARS-HSA) as well as its proteolytic fragments were added to tissue explant cultures and ABP formation followed by indirect ELISA using mAb to ABP. The response to small fragments was comparable to that induced by intact ARS HSA. Furthermore, the response to intact antigen was almost completely blocked by the non-toxic serine protease inhibitor Pefabloc, while the response to small fragments was only slightly reduced. The kinetics of response to intact antigen significantly differed from that induced by small (< 3 kDa) fragments. We suggest that proteolytic processing is involved in the stimulation of ABP formation. PMID- 8002049 TI - Immunolocalization of cyclophilin in normal and cyclosporin A-treated human lymphocytes. AB - A polyclonal rabbit antibody against a protein fraction (10-30 kDa) of human thymuses with a high CsA-binding activity of dominant protein cyclophilin (CPH) was prepared and characterized. In immunoblotting with the cell lysate from JURKAT T cell line, this antibody specifically reacted with 18-kDa protein corresponding to CPH. In indirect immunofluorescence the antibody visualized granular structures in JURKAT cells and human peripheral blood lymphocytes. In JURKAT cells cultivated with 1-2 micrograms of CsA per ml for 7 days a much weaker reaction of the antibody was found, compared with non-treated cells. In some CsA-treated cells the antibody visualized various 'star-like' or filamentous structures. A similar staining pattern has also been obtained in lymphocytes of the patients receiving CsA therapy. Complementary staining with rhodamine-tagged phalloidin revealed changes in F-actin distribution of CsA-treated JURKAT cells. In conclusion, the treatment with CsA induces dramatic changes of CPH cellular distribution, which may take part in the final therapeutic effect of the drug. PMID- 8002051 TI - Production of fibroblast proliferative cytokines from T lymphocytes stimulated by a B cell lymphoma line and their functional heterogeneity. AB - Human mononuclear leukocytes (MNL) produced several factors with fibroblast proliferation activity (FPA) for HFL-1, a human lung fibroblast cell line, when MNL were cocultured with irradiated BALL-1, a B cell lymphoma line (BCLL), but not with other BCLL. The cellular source of BALL-1-induced FPA seemed to be CD4 positive T lymphocytes. On isoelectric electrophoresis, major activity of BALL-1 induced FPA was detected in the fractions around pH 4-5, and minor activity was present in the fractions around pH 6-7. Major BALL-1-induced FPA consisted of at least 4 different fibroblast proliferation factors (FPFs) according to their molecular weight; 320-600 kDa (P-I), 50-110 kDa (P-II), 22-38 kDa (P-III) and 4.6 11 kDa (P-IV). P-I had affinity to heparin though the rest had little or no affinity. FPA of P-I was suppressed by an antibody against acidic FGF, and FPA of P-III was suppressed by an antibody against IL-6. On the other hand, FPA of P-II and P-IV was suppressed by none of the antibodies against cytokines with FPA, such as FGF, IL-4, IL-6, IFN-gamma, TGF-beta and TNF-alpha. It was thus suggested that P-I was acidic FGF, that P-III was IL-6, and that P-II and P-IV were different cytokines from those described above. Furthermore, it was found that P II and P-IV failed to exhibit proliferation activity for human umbilical vein endothelial cells (HUVEC).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8002052 TI - Expansion of kappa + B cells during the primary immune response to 4-hydroxy-3 nitrophenyl acetate in BALB/c mice. PMID- 8002053 TI - WHO Task Force Meeting on Mechanisms of Immunity to Malaria. Freiburg, Germany, 24-25 April 1993. PMID- 8002054 TI - Inducing protective immune responses against the sporozoite and liver stages of Plasmodium. AB - Work on vaccines against the pre-erythrocytic stages of the Plasmodium life cycle is based on the observation that immunization with irradiated sporozoites (IRR SPZ) is protective. Antibodies against several SPZ surface proteins can prevent SPZ from effectively invading hepatocytes; antibodies and cytolytic-T lymphocytes directed against at least 3 parasite proteins expressed in infected hepatocytes can kill infected hepatocytes; and cytokines can activate infected hepatocytes to kill the intracellular parasite. Work is in progress to identify additional pre erythrocytic parasite targets and to develop methods for optimally inducing protective immunity against SPZ and infected hepatocytes. The goal is to construct a vaccine that protects by inducing antibody and cellular immune responses against multiple parasite proteins. PMID- 8002055 TI - The immune response to the blood stages of Plasmodium in animal models. AB - Several models can be used to study the erythrocytic stages of Plasmodium in the vertebrate host. Although no single-model system reflects the human infection exactly, different systems taken together provide important information on the antigens necessary to stimulate protective immunity and the mechanisms of immunity and immunopathogenesis. Investigations, particularly in rodent models, have demonstrated the importance of CD4+ T cells in protective immunity to erythrocytic parasites and have shown that effector functions (Th1 and Th2) of these cells may play a role in parasite clearance. Because of the nature of the peptide-MHC interaction, animal models may not supply detailed information on the fine specificity of T-cell responses. However, immunisations of rodents and primates with a variety of recombinant proteins of Plasmodium will indicate the feasibility and limitations of using peptide vaccines in man. PMID- 8002056 TI - Clinical, hematological and electrophysiologic study of megaloblastic anemias. AB - Thirty one cases of megaloblastic anaemia were studied clinically and electrophysiologically. Eight patients had clinical evidence of peripheral neuropathy. MNCV, distal sensory latency, la fibre conduction velocity, proximal conduction velocity and H-reflex amplitude and latency were compared with fourteen age and sex matched healthy controls. MNCV, proximal conduction velocity and H-reflex amplitude were significantly decreased in anaemic subjects while distal sensory latency was increased. No change was seen in la fibre conduction velocity and H-reflex latency. There was no correlation between severity of anaemia and the electrophysiologic abnormalities. MNCV and la fibre conduction velocity improved after correction of anemia. PMID- 8002057 TI - Tuberculosis screening: usefulness of new KREATECH IgA ELISA test. AB - A total of 71 sera from 15 proved cases of pulmonary tuberculosis, 2 cases with doubtful radiological report and 54 suspected cases, contacts, donors etc. were subjected to Elisa IgG, IgM and IgA tests for tuberculosis, with a view to comparing the merits of IgA test with those of IgG and IgM. Kreatech IgA test which is claimed to indicate presence of active tuberculosis was positive in 13 of the proved cases and negative in both the doubtful cases. These preliminary results indicate that KREATECH IgA is a promising new ELISA test which can be a useful laboratory aid in the diagnosis of active tuberculosis, both pulmonary and extrapulmonary, for screening of suspected cases, and for monitoring cases undergoing therapy. PMID- 8002058 TI - Isolated traumatic rupture of the adductor longus muscle. AB - A rare case of traumatic rupture of Adductor longus muscle in a young Kabaddi player is presented. Excision of ruptured muscle mass was done. Maximum follow-up at eighteen months showed no disability. PMID- 8002059 TI - Iron and the developing brain. PMID- 8002060 TI - Advances in vaccines for typhoid fever. PMID- 8002061 TI - Morning steroid profile in children with congenital adrenal hyperplasia under different hydrocortisone schedules. AB - We studied 13 children with 21-hydroxyalse deficiency to explore the immediate potential suppressive effect of hydrocortisone dose schedule on the adrenal cortex. They were given 20 mg/m2 daily in a controlled trial. After random administration of a greater dose in the morning (7 patients) or at night (6 patients), we measured plasma levels of 17-hydroxyprogesterone, testosterone, and androstenedione at times-24, 0, 2, 4, and 6h. Considerable fluctuation of the steroid levels, unrelated to the drug intake, was observed. There was no statistically significant differences between the "morning dose" and "night dose" groups for any steroid. We conclude that; (i) the greater night dose did not avoid the 17-hydroxyprogesterone morning peaks, and (ii) the variation in plasma steroid levels is so marked that a single morning sample is unreliable to reflect the degree of adrenal suppression. PMID- 8002062 TI - Estimation of tissue DNA content in Wilm's tumour. AB - DNA genome, is affected by malignant processes. Estimation of DNA content was carried out biochemically using Gile's and Myer's technique to assess its prognostic value in 21 cases of Wilm's tumour. The DNA content of tumour tissue and normal adjoining renal tissue was estimated in each case. The DNA content was significantly higher in Wilm's tumour tissue as compared to normal renal tissue (p < 0.05). As the disease advanced, the DNA content of the tumour further increased. The tumours having unfavourable histology had significantly higher DNA content as compared to favourable histology cases (p < 0.001). Similarly, the patients who died because of the disease, had a very high DNA content as compared to those who survived. Further, it was seen that two fold increase in DNA content indicated advanced stage (III & IV), whereas a three fold or more increase indicated grave prognosis as it was usually seen in advanced stage with unfavourable histology and such cases died early. Thus, the DNA content estimation has a prognostic significance in Wilm's tumour. PMID- 8002063 TI - The posterior urethral valve uropathy: results of treatment. AB - Nineteen children treated for posterior urethral obstruction due to congenital valve in the University of Benin Teaching Hospital, Benin City, Nigeria, over a 9 year period have been analysed. Their ages ranged from birth to 12 years. Results show that associated kidney pathology may be irreversible even after successful excision of the valve. This determines the final prognosis, which is worse the younger the child at presentation. PMID- 8002064 TI - Surveillance of drug induced diseases in children. AB - A hospital based prospective study on drug induced diseases (DID) in children below 14 years of age was done for a duration of two years. A total number of 20,310 patients were examined in pediatric department during this period, out of which 204 (1.004%) patients were diagnosed as DID. Children with severe reactions were admitted in pediatric ward for in hospital intensive surveillance. The male:female ratio in DID was 1.2:1. DID were most common in neonates (24.51%). Erythmatous maculopapular rashes (67.12%) formed the most common pool of DID in neonates. Thrombophlebitis (41.56%) was most commonly seen in infants above 28 days of life, and in children up to 14 years of age. Out of 204 cases of DID, 9 (4.41%) died. Aplastic anemia was most morbid DID, as all the 7 patients of aplastic anemia died. Chloramphenicol was responsible for all the cases of aplastic anemia. Other two deaths were from erythma multiforme and C.C.F. The most commonly involved drugs, other substances and vaccines were baby powders, massage oils, ampicillin, co-trimoxazole, i.v. infusions (electrolytes and mannitol), DPT and measles vaccines. PMID- 8002065 TI - Storage disorders presenting like mucopolysaccharidosis. AB - The term dysostosis multiplex is specifically applied to the group of radiological features collectively found in a number of specific metabolic disorders including the mucopolysaccharidoses, mucolipidosis, mannosidosis, fucosidosis and several other rarer conditions. We report eight cases of mannosidosis, fucosidosis and mucolipidosis with special emphasis on the differentiation from the more common mucopolysaccharidoses. PMID- 8002066 TI - A clinical study of infants presenting to a mental retardation clinic. AB - Early detection has a central role in the prevention and management of mental retardation. The purpose of this present study is to delinerate the characteristics of developmentally delayed infants and their families attending Mental Retardation Clinic. The sample consisted of 101 infants who were registered in Mental Retardation Clinic of NIMHANS, Bangalore in 1988 constituting 12.5% of total registrations. Data was collected from case records. Majority of subjects were males, first or second born, 7 months or older, from a consanguineous lower or middle class family. Along with developmental delay, 60% had other complaints. Medical problems were reported in about half of the subjects and most had abnormalities on physical examination. Aetiology was discernible in 77.1%. Majority had associated physical disorder such as cerebral palsy, seizures and hearing and/or visual impairment. Around 17% came for follow up thrice or more, 43% dropped out after work-up. The main conclusions are that; (i) certain socio-demographic, personal and clinical variables influence treatment seeking, and (ii) developmental delay recognised in infancy tends to be associated with clear aetiologic factors and significant medical/neurologic problems. PMID- 8002067 TI - Assisted ventilation in neonates: the Manipal experience. AB - Case records of 68 newborns who required assisted ventilation over a 24 month period were reviewed. Fortyfour (64.7%) received intermittent mandatory ventilation, 10 (14.7%) received nasal CPAP and the remaining 14 (20.58%) received a combination of the above. Some of the indications for ventilation were infections (21), hyaline membrane disease (16), problems related to asphyxia (11), apnea of prematurity (10) and persistent pulmonary hypertension of newborn (5). The overall survival rate was 41.17%. In the CPAP group 90% (9/10) survived, while in the remaining survival was 32.7% (19/58). The best outcome was observed in persistent pulmonary hypertension of newborn (80%) followed by apnea of prematurity (70%) and hyaline membrane disease (43.75). Outcome was poor in conditions related to birth asphyxia (27.2%) and infections (19.05%). Survival rates were higher (44.4%) in babies weighing > 1500g at birth as compared to 40.9% in babies < 1500g. Babies less than 32 weeks gestation had a survival rate of 32% as compared to 46.5% in those over 32 weeks. This difference was not statistically significant. Complications were seen in 12/68 patients (17.6%). Pneumothorax was the commonest followed by sepsis, intraventricular hemorrhage and blocked endotracheal tubes. Babies with hyaline membrane disease had the highest incidence of complications. Analysis of the data with regard to the indications, outcome and complications is presented. PMID- 8002068 TI - Liver transplantation from living related donors: review of world experience and its implications for India. AB - Living related liver transplantation (LRLT) was made possible because of a better understanding of the anatomy of the liver and advances made in hepatic surgical techniques. It was developed to reduce the waiting period for pediatric recipients. In countries like Japan, which do not have brain stem death legislation, LRLT is the only modality available for treating end stage liver disease. The world experience has shown that LRLT has been successfully performed in a variety of conditions leading to acute and chronic liver failure not only in children, but in young adults as well. The initial results of LRLT appear to be better than liver transplantation from cadaveric organs in terms of graft survival and function. Donor safety has been of prime concern. LRLT has tremendous potential in India with or without the brain stem death legislation. Liver transplantation has not been performed in India although the need and expertise for it exists. PMID- 8002069 TI - Elevated polymorphonuclear phagocytic function in thalassemia patients by chemiluminescence. AB - Twenty five patients with beta thalassemia major, with no evidence of infection were evaluated for their polymorphonuclear cell (PMN) metabolic function and serum opsonic activity by chemiluminescence assay. These were divided into Group I of normal adults (n = 21), Group II thalassemia major < 5 years (n = 9) and Group III thalassemia major > 5 years (n = 16). The ability of the chemiluminescence assay (CL) to reflect opsonic and phagocytic dysfunction suggested its potential application in the evaluation of phagocytic function. The peak count of Group I was (1.07 +/- 0.24 x 10(-5)), Group II (1.60 +/- 0.83 x 10( 5)) and Group III was (2.71 +/- 0.98 x 10(-5)) respectively in the presence of autologous sera. The peak count compared between Group I and III was found to be statistically significant (p < 0.05). The peak count of Group I and II when compared showed a trend in the increase activity not statistically significant. The polymorph function of all the groups were compared with autologous serum as well as normal serum. There was no increase in polymorph function of Group III in the presence of thalassemia serum, nor any decrease in the polymorph function of thalassemia patients of Group II and III. This concluded that polymorphs of thalassemia patients are active in the presence of autologous as well as normal serum. The increased activity of thalassemia polymorphs may be due to antigenic stimulation which may be due to multiple transfusion and not due to circulating iron load. PMID- 8002070 TI - Bone injuries during delivery. AB - Bone injuries during the process of delivery were studied among 34, 946 live born babies over a 11 period. There were 35 cases of bone injuries giving an incidence of 1 per 1,000 live births. Clavicle was the commonest bone fractured (45.7%) followed by humerus (20%), femur (14.3%) and depressed skull fracture (11.4%) in the order of frequency. There was one case each of orbital fracture, epiphyseal separation of lower end of femur and dislocation of elbow joint. Lack of antenatal care, malpresentation often leading to obstructed labour and operative deliveries were found to be risk factors for bone injuries. Meconium stained liquor and birth asphyxia were more commonly associated with bone injuries than control cases. Cases with injuries had longer hospital stay and higher mortality. Improving the health infrastructure at the peripheral level with early identification of high risk mothers and their appropriate management can bring down the incidence of bone injuries. PMID- 8002072 TI - Hodgkin's disease with nephrotic syndrome. PMID- 8002071 TI - Iodine deficiency disorders in school children of Sikkim. AB - Sikkim is a small state in the eastern Himalayas. A survey was conducted to determine the prevalence of iodine deficiency disorders in the state. A two stage sampling procedure was adopted. In stage one, all villages in the state were listed and 249 were randomly selected for the survey. In stage two, households, were randomly selected from the selected villages using the electoral lists. The basic sampling unit was a household and all members of the households were studied. A total of 17,837 subjects were studied from 3,197 households of 249 villages. Overall prevalence of goitre and cretinism in the community as a whole, were 54.03% and 3.46% respectively. Of the population studied, 5939 were children in the age group of 5 to 16 years. There were 3,005 boys and 2,934 girls. Goitre was detected in 3,381 (56.9%). Goitre prevalence in the boys was 55.4% and in girls it was 58.5% (p = < 0.05). Grade I goitre was seen in 2,472 (73.1%), grade II in 888 (26.3%) and grade III in 21 (0.6%). Endemic cretinism was diagnosed in 175 subjects (2.9%). Cretinism prevalence in the boys was 3.1%, and in girls in was 2.8% and this difference was not significant. Neurological; cretinism was the predominant form (98.3%). Estimation of urinary iodine concentration in 167 subjects revealed the mean concentration to be 3.64 u/dl (SD 2.47). The median value was ug/dl indicating the skewed distribution of the urinary iodine concentration. The study shows the existence of severe iodine deficiency in the school-aged children of Sikkim.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8002073 TI - Fibrodysplasia ossificans progressiva. PMID- 8002075 TI - Foreign body of prolonged duration in the bronchus--an unusual case. PMID- 8002074 TI - A case of hypogonadism with a translocation: t(4; 12) (q25; q24.2). PMID- 8002076 TI - Congenital tuberculosis: under diagnosed or under reported? PMID- 8002077 TI - Adrenal hemorrhage in asphyxiated neonates and the importance of ultrasonography. PMID- 8002079 TI - More--not always merrier! PMID- 8002078 TI - Early onset juvenile diabetes mellitus controlled with nicotinic acid therapy. PMID- 8002080 TI - Mixed gonadal dysgenesis with 45, X/46, XX/46, XY mosaicism. PMID- 8002081 TI - Resistant Pneumococcus: a worldwide problem. PMID- 8002082 TI - Increased levels of tumor necrosis factor alpha (TNF-alpha) and interleukin 1 beta (IL-1 beta) in tracheal aspirates of newborns with pneumonia. AB - Pneumonia is one of the major sites of infection in ventilated newborns. We investigated whether the cytokines IL-1 beta and TNF-alpha are detectable in tracheal aspirates of newborns with pneumonia as a diagnostic marker. All 12 infants with pneumonia had elevated levels of IL-1 beta (range 30-300 pg/ml) and TNF-alpha (range 60-680 pg/ml), whereas control infants (n = 21; respiratory distress syndrome, very low birth weight or infants intubated preoperatively) had no detectable levels of IL-1 beta or TNF-alpha. In vitro investigations with mononuclear cells of umbilical cord blood were performed to rule out that exogenously added surfactant influences IL-1 beta and TNF-alpha production. It is concluded that IL-1 beta and TNF-alpha are important and specific mediators of neonatal pneumonia which may be of diagnostic importance. PMID- 8002083 TI - Early- and late-onset pelvic inflammatory disease among women with cervical Chlamydia trachomatis infection at the time of induced abortion--a follow-up study. AB - After termination of a double-blind, randomized study on erythromycin in the prevention of post-abortion infection, 34 women (14 treated with erythromycin, 20 not treated with erythromycin) harbouring Chlamydia trachomatis were followed up within 6 weeks and again 2 to 24 months after the abortion in order to detect an early- and late-onset pelvic inflammatory disease (PID). For statistical analysis survival analysis by Kaplan-Meir estimates and Mantel-Cox test were carried out. Untreated women with C. trachomatis infection at the time of abortion had a cumulative risk of 72% of developing early and/or late PID, if observed for 24 months. This cumulative risk was significantly reduced to 8% if the C. trachomatis infection was treated at the time of the abortion. Screening for and treatment of C. trachomatis is warranted, especially in women < or = 25 years old, to avoid early and late-onset PID after induced first trimester abortion. PMID- 8002084 TI - Fluconazole in the management of fungal urinary tract infections. AB - The presence of Candida in the urine is not considered normal but does not necessarily indicate urinary tract infection. On the other hand, yeasts in urine cultures might be the first symptom of systemic fungal infections. Despite the difficulties that exist, establishment of an accurate diagnosis is important especially in high risk patients because ascending infections may lead to disseminated disease. Amphotericin B bladder irrigation is a common mode of therapy for fungal urinary tract infection, although no specific guidelines exist as to the use of the procedure. The pharmacokinetic parameters possessed by the triazole antifungal agent fluconazole make it a candidate for treating fungal urinary tract infections. Five case reports and 99 patients reported in several small studies were reviewed. As evident from these reports, fluconazole appears to be of value in the treatment of both uncomplicated and complicated fungal urinary tract infections. PMID- 8002085 TI - Bacterial colonisation with Xanthomonas maltophilia--a retrospective study in a cystic fibrosis patient population. AB - Xanthomonas maltophilia was isolated from 25 of 150 patients with cystic fibrosis during a period of 10 years (1983-1992). Twelve patients harboured X. maltophilia chronically, i.e. repeatedly for more than 6 months. No predisposing factors for the colonisation could be identified by studying the clinical and laboratory data of the patients, including preceding and concurrent bacterial colonisation with other bacteria, antibacterial treatments, pulmonary function and biochemical markers. Up to 2 years after the chronic colonisation was established no clinical deterioration could be verified, but the patients with X. maltophilia generally had a worse lung function at the latest follow-up (2-7 years after colonisation) than controls colonised with Pseudomonas aeruginosa (p < 0.05). Our data imply that X. maltophilia is a pathogen and the colonisation appears to follow the same pattern as the colonisation by P. aeruginosa. The development of resistance to different antibiotics, as revealed by analysis of the inhibition zones, was related to antibacterial treatment courses. X. maltophilia showed reduced sensitivity to the most commonly used antibiotics, ceftazidime and tobramycin. PMID- 8002086 TI - Infections in critically ill patients: experience in MICU at a major teaching hospital. AB - During a one-year period 105 patients suffering a total of 134 infectious episodes were studied prospectively in the medical intensive care unit (MICU). These patients included 54 male and 51 female patients, age ranging from 14 to 100 years (median = 54 years). The overall incidence of infection was 46.7%. Infections acquired in medical wards accounted for 47.8% of the total, followed by community-acquired infections in 27.0%, and MICU-acquired infections in 25.2% of the cases. The most frequent infections were pneumonia and septicaemia accounting for 88% of the total, whereas urinary tract (4.4%), gastrointestinal tract (5.0%), skin and wound infections (2.5%) constituted only 11.5%. The pathogens mainly involved were gram-negative rods, Staphylococcus spp. and Streptococcus pneumoniae. However, in community-acquired pneumonia, the major pathogens were gram-negative rods. In addition, Mycobacterium tuberculosis was an important cause of pneumonia in these patients. The majority of patients had a monoinfection; multiple pathogens were isolated in 11.9% of the episodes. The overall mortality was 46.7%. Several factors that influenced the mortality in these patients were analyzed. Early recognition of these factors may reduce morbidity and mortality. PMID- 8002087 TI - A randomized clinical trial of ceftriaxone and teicoplanin versus ceftazidime and teicoplanin as antibiotic therapy in febrile neutropenic cancer patients and bone marrow transplant recipients. AB - A prospective, randomized clinical trial comparing combination therapy with ceftriaxone and teicoplanin versus ceftazidime and teicoplanin in the treatment of febrile episodes in neutropenic cancer patients and bone marrow transplant recipients was performed. One hundred and two patients were randomized, but two patients were considered unevaluable for efficacy, and three patients were withdrawn due to incorrect randomization. Of the remaining 97 patients, infection resolved without modification of therapy in 31/49 (63%) patients treated with ceftriaxone/teicoplanin versus 27/48 (56%) patients treated with ceftazidime/teicoplanin (P = 0.48). Of all 97 patients treated therapy was modified in 18/49 (36%) with ceftriaxone/teicoplanin and 21/48 (43%) with ceftazidime/teicoplanin. Nineteen patients treated with ceftriaxone/teicoplanin received netilmicin and 21 patients treated with ceftazidime/teicoplanin also received netilmicin according to the study design (escalation therapy). When netilmicin was added infection resolved in 78% of patients treated with ceftriaxone/teicoplanin versus 84% of those treated with ceftazidime/teicoplanin. It was concluded that combination therapy with ceftriaxone/teicoplanin is an alternative to combination therapy with ceftazidime/teicoplanin, and has the advantage of once daily administration. PMID- 8002089 TI - Impaired neutrophil function in the cutaneous form of anthrax. AB - Spontaneous and Bacillus anthracis induced luminol-dependent chemiluminescence of neutrophils was studied in six patients with the cutaneous form of anthrax. Spontaneous chemiluminescence in anthrax was decreased compared to the healthy controls (p < 0.05). B. anthracis, opsonized by complement-containing sera from patients, induced chemiluminescence in neutrophils from control donors but not from patients. B. anthracis, opsonized by complement-free sera from the patients, did not cause an increase in chemiluminescence response in either the patient or the control neutrophils. Also, B. anthracis, opsonized with normal sera and nonopsonized, did not induce chemiluminescence in either patient or control neutrophils. It was concluded that oxidative metabolism by neutrophils is impaired in anthrax, whereas the functional capacity of antibodies seems to be unaffected. PMID- 8002088 TI - Prolonged treatment of chronic Pseudomonas aeruginosa osteomyelitis with a combination of two effective antibiotics. AB - Emergence of Pseudomonas aeruginosa resistant to antibiotic monotherapy is one of the causes of therapeutic failure in chronic P. aeruginosa osteomyelitis. We report 15 cases of chronic (> 3 months of evolution) biopsy culture proven P. aeruginosa osteomyelitis included in an open prospective study evaluating the efficacy of prolonged treatment (> 4 months) with two effective antibiotics in combination. Mean post-treatment follow-up was 38 months. A regimen of cefsulodin in combination with oral ofloxacin was used for six patients, cefsulodin pefloxacin for three patients, cefsulodin-ciprofloxacin for one patient, piperacillin-pefloxacin for one patient, cefsulodin-fosfomycin for one patient, imipenem-ciprofloxacin for two patients and amoxicillin-ciprofloxacin-fosfomycin for one patient as home therapy. The clinical cure rate of 73% and bacteriological cure rate of 93% are far superior to those previously described in the literature. We did not observe adverse drug reactions. We think that a prolonged use of two effective antibiotics in combination is a safe and improved therapeutic schedule for chronic P. aeruginosa osteomyelitis. PMID- 8002090 TI - Pancreatic tuberculosis mimicking pancreatic head carcinoma: a case report and review of the literature. AB - A 24-year-old man presented with vague abdominal fullness and a mild epigastric dull pain for about 3 months was found to have a pancreatic head tumor at a medical center 2 months ago. He came to our hospital for further treatment. Ultrasonography, endoscopic retrograde cholangiopancreatography (ERCP) and abdominal computed tomography (CT) all revealede a pancreatic head tumor. Laparotomy was performed because pancreatic head carcinoma was highly suspected. Indurated mass in the pancreatic head, enlarged lymph nodes and white tubercles on the intestine proved to be tuberculosis on histological examination of a frozen section. Acid fast bacilli were also found. The patient was given antituberculous therapy and is now doing well. To avoid unnecessary laparotomy, CT, echo-guided percutaneous aspiration cytology or biopsy and culture of the tissue for mycobacteria should be done in a patient with pancreatic mass, especially in a region where pulmonary and abdominal tuberculosis are common. PMID- 8002091 TI - Continuous infusion of acyclovir is more effective than discontinuous infusion for treatment of genital herpes in an immunocompromised patient. PMID- 8002092 TI - Bacteremia caused by Ochrobactrum anthropi in an immunocompromised child. PMID- 8002093 TI - Multicenter evaluation of a novel quantification method for rubella and toxoplasmosis antibodies. AB - Antibody quantification by EIA is possible without a standard curve. Following the so-called alpha method only one test dilution is used, the resulting absorbance is corrected and the IU/ml will be calculated by means of a mathematical formula. This new kind of a single point measurement was evaluated in seven independent laboratories by comparison with commercial EIAs using a standard curve or a titer calibration line. For the quantification of IgG against rubella virus this study comprised 1,480 individual samples and three comparison EIAs. For IgG against Toxoplasma gondii a total of 743 samples was evaluated in two comparison tests. The results obtained by the alpha method show a precision and accuracy more than sufficient for routine testings. Also the technical expenses and reagent costs were reduced. Prerequisites and limitations are discussed against the background of the problem of immune status definition. PMID- 8002094 TI - Bactericidal activity of cefpirome (HR 810) against 513 gram-negative bacteria isolated from blood of septicemic patients. AB - The profile of antibacterial activity of cefpirome was compared with that of nine other antimicrobial agents against 513 gram-negative bacteria isolated from septicemic patients. All strains were evaluated for their sensitivity by disc diffusion and broth dilution tests (MIC and MBC). Cefpirome was compared to cefazolin, cefuroxime, ceftazidime, ceftriaxone, aztreonam, imipenem, ticarcillin, tobramycin and ciprofloxacin. Among the five cephalosporins tested in this study, cefpirome was the most active against all isolates. The MIC50 and MIC90 of eight isolates of Acinetobacter calcoaceticus were 2 and 4 mg/l and those of 89 Pseudomonas aeruginosa were 2 and 8 mg/l, respectively. The MIC90 values of cefpirome for all other groups of bacteria were < or = 1 mg/l. The activity of cefpirome against gram-negative bacteria is at least as good as that of aztreonam and imipenem. The only drug showing a better profile of activity than cefpirome is ciprofloxacin. The scattergram of the 513 isolates for cefpirome MICs and inhibitory zones with the 30 micrograms disc, showed that only eight isolates were not susceptible to cefpirome. These data suggest that the in vitro activity of cefpirome is comparable to if not better than that of other beta-lactams and tobramycin. PMID- 8002095 TI - Combination effect of meropenem with aminoglycosides and teicoplanin on Pseudomonas and enterococci. AB - The in vitro activity of meropenem, a new carbapenem, and the combination effect with netilmicin, tobramycin, gentamicin, and teicoplanin against Pseudomonas spp. and enterococci was studied. Meropenem showed very good in vitro activity against Pseudomonas aeruginosa (MIC90 2 mg/l) and good to moderate activity against Pseudomonas putida (MIC90 4 mg/l) and Enterococcus faecalis (MIC90 8 mg/l). Aminoglycosides were highly active against P. putida (MIC90 0.5 mg/l), but showed only moderate activity against P. aeruginosa. The synergistic effect of meropenem was shown in combination with teicoplanin against E. faecalis (40%). No Pseudomonas strains were inhibited by the synergistic effect of meropenem with aminoglycosides. No antagonism occurred with any of the combinations. PMID- 8002096 TI - Nursing assistant burnout and the cognitively impaired elderly. AB - This article employs the cognitive appraisal model to examine the experience of burnout in a random sample of nursing assistants (N = 245). The three subscales of Maslach's Burnout Inventory--Emotional Exhaustion, Personal Accomplishment, Depersonalization--serve as the dependent variables in this study. The study found that both stressor and appraisal variables influence feelings of burnout. The stressor variable, frequency of disturbing patient behaviors, best explained feelings of reduced Personal Accomplishment. The appraisal variable, reaction to patient behaviors, best explained Emotional Exhaustion and contributed to the explanation of reduced Personal Accomplishment. Age, minutes spent giving physical care, appraisal of work tasks, and reaction to patient behavior, explained Depersonalization. The study found support for the cognitive appraisal model in that appraisal played an important role in determining burnout. The article concludes with some suggestions for relief of nursing assistant burnout. PMID- 8002097 TI - Age and skill differences in adaptive competence. AB - Previous research has documented qualitative changes in certain cognitive abilities during the older adult years, such as in short-term memory, perceptual and motor skills, and attentional capacities. Other work has suggested that a number of significant age-related changes, across a variety of cognitive abilities, are based on social experiences, such as occupational or recreational activities. The current study is based on earlier research by Perlmutter and her colleagues (1990) and examines age and skill-related differences among adults engaged in a social-recreational activity. BINGO players, ranging in age from nineteen to seventy-four, and having from less than two months to over twenty years of playing experience, were given a variety of psychometric, cognitive, and experimental measures. The participants were also observed as they played real BINGO games. No age-related differences were found on the psychometric or memory measures, suggesting that BINGO playing experience may have positive benefits for many older adults. Skilled players at all age levels were found to be more efficient in their game-playing actions. The oldest and most experienced players did not differ from the younger, equally experienced, players on the cognitive and skill-based tasks. These findings demonstrate the need to investigate adaptive competence in those situations in which social-environmental factors play a role in enhancing older adults' cognitive skills. PMID- 8002098 TI - Peace Corps service as a turning point. AB - This is a longitudinal study of twenty-one U.S. Peace Corps Volunteers, first interviewed in the mid-1960s during their tour of service in the Republic of the Philippines and then twenty years later as middle-aged adults. Life events reported after their service and the high degree of response agreement in the two interviews confirm that their Peace Corps experience constituted a turning point in their life courses. The study reviews the literature on turning points, proposes an appropriate definition for the concept, identifies conditions that promote turning points, especially for youth, and indicates directions for future research. PMID- 8002099 TI - Social contact patterns and satisfaction with retirement of women in dual career/earner families. AB - The authors conducted an empirical study in 1990 of 611 mature women in dual career/earner families who are retired from a work position in the field of education. We test twelve hypotheses that relate frequency of contact, kind of social contact and perceived gap between desired and frequency of actual social contact to satisfaction with women's timing of retirement and leisure. Nine of the twelve hypotheses were confirmed. Women who have more frequent and a greater variety of social contact are more satisfied with the timing of their retirement and their leisure than those who have less contact. The wider the gap between desired and actual frequency contact with specific groups the less satisfied will women be with their leisure experience, their amount of leisure time, and their timing of retirement. PMID- 8002100 TI - The influence of separation orientation on life satisfaction in the elderly. AB - Good health, involvement in social activity, and the presence of a confidant have all been found to be important factors for life satisfaction of the elderly. However, there is a significant minority of the elderly for whom these findings do not hold. The results of this study indicate that individuals' separation orientation helps explain the differential impact of important environmental factors on life satisfaction. Those who are overly dependent tend to be more adversely affected by poor self-rated health and inadequate formal activity than balanced or overly self-sufficient participants. In contrast, the presence of a confidant was associated with higher life satisfaction scores for overly dependent participants, but was associated with decreased life satisfaction for overly self-sufficient participants. PMID- 8002101 TI - Aging and generational patterns of alcohol consumption among Mexican Americans, Cuban Americans and mainland Puerto Ricans. AB - The relationship between aging and drinking among U.S. Hispanics is not well understood. The present study used data from the Hispanic Health and Nutrition Examination Survey to describe life-course patterns of alcohol consumption among Mexican Americans, Cuban Americans, and Puerto Ricans residing in the mainland United States. Age differences in patterns of consumption among Mexican American and Puerto Rican males were found to reflect aging effects, as evidenced by increasing percentages of former drinkers coupled with consistently low percentages of abstainers at all ages. Among Cuban males, cohort effects were evidenced for middle-aged and older men by a continuation of low rates from younger years, as well as a sharp difference between the rates of the middle-aged and older cohorts and those of the younger cohort. Age differences among all three groups of females were found to reflect cohort effects, as evidenced by large proportions of life-long abstainers across all age cohorts. PMID- 8002102 TI - Spectral estimation of EEG signals using cascaded inverse filters. AB - While most of the studies on application of autoregressive (AR) methods to EEG signals have considered direct modelling of EEG data, this paper considers the inverse problem of passing the EEG signal through an inverse filter and shows how such inverse filters when cascaded give an improved spectral estimate of the input data. It is shown how a proper choice of model orders of such cascaded inverse filters leads to better spectral estimation of an EEG signal than by conventional AR filters. An EEG signal, when first passed through a low order inverse filter, actually results in a signal with reduced dynamic range and thus a second inverse filter with higher order gives much better spectral peaks. In fact, such cascading operation reduces the problem of ill conditioning of the autocorrelation matrix thus yielding better results. The analysis has been performed using real EEG data. PMID- 8002103 TI - Developing blood flow in the entrance region of an artery. AB - Presented herein are the studies of the flow behaviour of blood in the entrance region of a segment of an artery. The artery has an axisymmetric mild stenosis developed right from the entry cross section. The blood has been represented by a Bhingham fluid model which also takes the core region, formed due to axial migration of the red blood cells, into account. The flow in the artery has been divided into two regions developing boundary layer and a central core region. A fourth degree velocity profile satisfying the boundary conditions at the wall and the matching conditions at the core and the boundary layer interface is introduced in the governing momentum integral equation. The indicated integration provides a relation for the boundary layer thickness for each axial position. The results for the pressure distribution, entrance length and the wall shear stresses are discussed for the various values of the parameters involved in the analysis. The analysis predicts that the entrance length increases as the stenosis grows and therefore the heart has to put in more energy into transporting blood. It seems that there is some inbuilt mechanism which keeps the entry region of every segment to a minimum in normal arteries at each junction. This length increases in pathological states leading to various types of hypertensive diseases due to the formation and growth of the stenosis. PMID- 8002104 TI - Teaching cancer chemotherapy by means of a computer simulation. AB - BIO-1014 is an educational computer-based program written in TURBO PASCAL 3.01 which simulates experiments of antitumour activity. Basically, this program offers the user the possibility of checking the therapeutical efficiency of anticancer drugs as applied to different tumors, but many other types of experiment can be also performed with BIO-1014. Drugs such as methotrexate, cyclophosphamide and arabinosylcytosine can be tested on the following tumors: sarcoma, carcinoma, leukemia and melanoma. The dose, the number of treatments per day, the total number of treatments and the time interval between the treatments are the parameters to be adjusted for each therapeutical schedule. Tumoral growth, cause of death and survival are among the results that are generated after each simulation. These results are either tabulated or plotted. In addition, four statistical tests have also been integrated to the program in order to provide with a way to check whether or not there is a significant difference in terms of survival between two groups of mice differently treated. Furthermore, the program has been elaborated to also consider some physiological phenomena met within an anticancer drug screening programme. The potential and the performance of the program BIO-1014 is presented and discussed. PMID- 8002105 TI - A decision support system for AIDS intervention and prevention. AB - In recent years, the importance of information systems has been identified as a vital issue to continuing success in AIDS intervention and prevention (AIP). The advances in information technology have resulted in integrative information systems including decision support systems (DSS). The concept of DSS for AIP was created at the intersection of two trends. The first trend was a growing belief that AIP information systems are successful in automating operations in AIP programs. The second was a continuing improvement in modeling and software development in the AIP area. This paper presents an integrated DSS for AIP. The system is integrated with a database and achieves its efficiency by incorporating various algorithms and models to support AIP decision processes. The application examples include screening AIDS-risky behaviors, evaluating educational interventions, and scheduling AIP sessions. The implementation results present evidence of the usefulness of the system in AIP. PMID- 8002106 TI - GTRACK: a PC program for computing Goldstein's growth constancy index and an alternative measure of tracking. AB - This paper reviews Goldstein's 'growth constancy index,' Xi, a measure of tracking which can be used to determine whether or not individuals maintain their relative positions in the distribution of a given measurement as that distribution changes over time. We suggest that Xi is an appropriate measure of tracking when the (standardized) measurements arise in the context of a Model I ANOVA, but that the intraclass correlation coefficient, rI, may be preferred when a Model II ANOVA is applicable. We also describe--and make available--a PC program which allows the user to choose between Model I and Model II, and computes the appropriate tracking index and confidence intervals for the corresponding parameter. PMID- 8002107 TI - [The place of traction and the anterior approach in the surgical treatment of kyphosis and kyphoscoliosis in children using C.D. instrumentation]. AB - The surgical treatment of kyphosis and kyphoscoliosis in children or adolescents using the Cotrel-Dubousset (C. D.) instrument through a posterior approach may often need a further anterior procedure either before or after. We have reviewed 20 adolescents who were operated on at l'Hopital Saint Vincent de Paul since 1983. Our choice of management was determined by consideration of the aetiology, the age, the degree of angulation and the suppleness of the kyphotic spine in hyperextension on the operating table. The use of preoperative traction for a mean of 25 days gained an improvement of 14% of the final correction. It was used in the curves which were most pronounced, usually high thoracic curves which lacked suppleness in the lumbar spine and which were stiff on the table. The anterior approach was not indicated in long double dorso-lumbar curves, usually of idiopathic origin, which had already reached an advanced stage of development. It was necessary in severe angular kyphoses which were unstable or had marked anterior stiffness. It was sometimes used in younger patients with kyphoscoliosis in which it was difficult to assess the state of maturity. After operation the kyphosis was corrected by up to 73% in simply kyphoses, 66% in kyphoscoliosis and 59% in scolio-kyphosis. After operation we were usually able to mobilise patients without a corset. PMID- 8002108 TI - Anterior decompression and fusion for cervical myeloradiculopathy secondary to ossification of the posterior ligament. AB - The authors reviewed 85 patients who had undergone anterior decompression and cervical fusion for myeloradiculopathy due to ossification of the posterior longitudinal ligament. There were 72 males and 13 females; the average follow up was for 8.3 years. Sixteen patients (group I) underwent one vertebra subtotal spondylectomy with fusion, 58 (group II) two vertebra subtotal spondylectomy, and 11 (group III) three vertebra subtotal spondylectomy. Neurological recovery was assessed on the grading system of the Japanese Orthopaedic Association. The patients in group I had an average improvement of 75%, in group II 72% and in group III 23%. The severity of compromise of the spinal cord did not affect the postoperative improvement. Duration of disease, previous injury and advanced neurological symptoms all affected neurological recovery. Spondylectomy of at most two vertebrae, with fusion, is recommended for ossification of the posterior longitudinal ligament. If there is more extensive involvement laminoplasty may be indicated. PMID- 8002109 TI - Anterior cruciate ligament reconstruction with fresh-frozen patellar tendon allografts. AB - A prospective study was performed on 30 patients who underwent an anterior cruciate ligament reconstruction with fresh-frozen patellar tendon allograft. An arthroscopic technique alone was used in 10 patients, and in the other 20 patients this was combined with a miniarthrotomy. After a mean follow up of 35 months, the overall functional results were satisfactory in 85%. There were no cases of infection, disease transmission or tissue rejection. Fresh-frozen patellar tendon allografts are a good method of anterior cruciate reconstruction. PMID- 8002110 TI - Bone mineral assessment by dual-energy X-ray absorptiometry in patients with coxarthrosis. AB - Forty patients with unilateral osteoarthritis of the hip were studied with dual energy X-ray absorptiometry to quantify disuse osteopenia in their affected leg by examining the proximal femur and tibia. Bone loss was assessed as a percentage of the contralateral value which compares bone mineral density of the affected and normal sides. The percentage contralateral value in the femoral neck and Ward's triangle was 113% and 118% respectively, while that in the tibia was 75%. Bone loss in the proximal tibia of the affected leg could be of value in assessing gait since it correlates with the gait parameters on the hip rating scale. By contrast, bone mineral increase in the proximal femur and correlates only with the degree of valgus deformity of the femoral neck. PMID- 8002111 TI - The implantation of cartilaginous and periosteal tissue into growth plate defects. AB - This experimental study reports the results of implantation of cartilaginous and periosteal tissues into growth plate defects in the tibiae of sheep. When no material was used, the defect rapidly filled with marrow-like tissue. When cartilage from the margin of the secondary centre of ossification was implanted, endochondral ossification continued and no shortening or deformity resulted. Implantation of periosteum with or without reconstructed peripheral tissues resulted in the formation of a bony bridge which led to a 32% inhibition of longitudinal growth and a 12 degrees varus deformity in the absence of peripheral connective tissues. After reconstruction with these tissues, the inhibition of longitudinal growth was 47% with a 28 degrees varus deformity. The chondroprogenitor cells in the implanted tissues cannot change phenotypic expression. Periosteum has a strong potential for bone formation after it has been implanted. PMID- 8002112 TI - Regeneration of perineurium after nerve injury and autografting. An experimental study. AB - Regeneration of the perineurium after crush injury to the rat sciatic nerve and after autografting was studied in an experimental model. After injury, fibroblast like cells formed compartments inside the funiculus which gradually acquired the characteristics of the perineurial cell. After grafting, the pattern of perineural regeneration depended on the degree of Schwann cell damage. In the graft and distal nerve trunk the epineurium degenerated and disappeared and new perineural tissue was formed by endoneurial fibroblasts from the inside of the funiculus. At the suture line, fibroblasts encircled the regenerating axons and the Schwann cells to form new compartments resulting in a large number of minifasciles of regenerating nerve. The function of the perineurium as a diffusion barrier was restored satisfactorily in the crushed nerve, although there was no satisfactory repair at 30 weeks after nerve grafting. PMID- 8002113 TI - Dorsal dislocation of the first metatarsophalangeal joint. AB - We report 3 cases of dorsal dislocation of the first metatarsophalangeal joint treated by closed reduction. Associated dislocation of the sesamoid complex may make reduction difficult. We suggest a modification of Jahss's classification and have confirmed our findings in amputation specimens. PMID- 8002115 TI - Primary leiomyosarcoma or leiomyoma of the pubic bone? A case report. AB - We report a case of what appeared to be a primary leiomyosarcoma of the left pubic bone of a female aged 23 years. Forty-eight cases of the tumour have been recorded in the literature since 1944, only two of which were in the pelvis. The tumour in our patient was treated by curettage and there was no recurrence in the following 3 years. The tumour cells showed only mild cellular atypism and 2 to 3 mitoses per 10 high-power fields. These finding suggest that the tumour might be an extremely rare leiomyoma of bone. PMID- 8002114 TI - In vitro assay of the invasive potential of malignant bone and soft tissue tumours through basement membranes. AB - We have used reconstituted basement membrane molecules which have formed into barriers in order to investigate the invasive potential of malignant bone and soft tissue tumour cells in vitro. A number of cell lines established from human malignant tumours demonstrated a high degree of invasiveness, although fibroblasts showed no ability to penetrate the basement membrane barrier. H-ras oncogene transfected cells into the fibroblasts were much more invasive than the parent lines. Primary cultures of malignant tumour cells demonstrated invasiveness, while those of nonmetastatic cells and fibroblasts did not. The binding of tumour cells to laminin in the basement membranes was found to induce secretion of collagenase and motility which are crucial factors for invasion. A synthetic peptide, Tyr-Ile-Gly-Ser-Arg, was able to suppress the invasiveness of HT1080 human fibrosarcoma cells, and also reduced lung colonisation in vitro. The results suggest that the in vitro assay was useful, firstly to determine the invasive potential, secondly to investigate the mechanism of invasion, and finally to development treatment against invasion and metastases. PMID- 8002116 TI - Gonadal hormones and semen quality in male runners. A volume threshold effect of endurance training. AB - Eleven high mileage runners (HR) (108.0 +/- 4.5 km.wk-1), 9 moderate mileage runners (MR) (54.2 +/- 3.7 km.wk-1) and 10 sedentary controls (SC) of similar age (28.3 +/- 1.5 yr) were studied to evaluate the effects of volume of endurance training on reproductive function in male runners. Levels of reproductive, adrenal and thyroid hormones were measured during a 1-hr period of serial blood sampling (q20 min) and urinary excretion of 24-hr luteinizing hormone (uLH) was determined on two separate days. Semen exams and sperm penetration of standard cervical mucus (Penetrak) were performed 2-5 times. Levels of total testosterone (TT) and free testosterone (FT) were significantly lower in HR (15.3 +/- 1.3 nmol.l-1 and 60.2 +/- 5.1 pmol.l-1) compared to MR (21.4 +/- 1.6 nmol.l-1 and 86.0 +/- 6.1 pmol.l-1) and SC (19.5 +/- 0.9 nmol.l-1 and 75.9 +/- 3.6 pmol.l-1). No differences (p > 0.05) were found in uLH, serum LH, follicle-stimulating hormone (FSH), and prolactin (PRL) among the three groups. No other hormonal differences (p > 0.05) were observed among the groups. Total motile sperm count and density were lower (p < 0.05) in HR than SC. Decreased (p < 0.0006) sperm motility and an increased (p < 0.004) population of immature sperm and round cells were observed in HR compared to MR and SC. Sperm penetration of bovine cervical mucus was also decreased (p < 0.024) in HR compared to SC. Volume of training, defined by km.wk-1 run, was significantly correlated to sperm motility, density and number of round cells.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8002117 TI - Impaired high-intensity cycling performance time at low levels of dehydration. AB - On two separate occasions six trained subjects (peak oxygen consumption [VO2peak] 4.41/min) rode for 60 min at 70% of VO2peak and then to exhaustion at 90% of VO2peak to determine the effects of mild dehydration on high-intensity cycling performance time in the heat (32 degrees C, 60% relative humidity, wind speed 3 km/h). In one trial (F) subjects ingested a 400 ml bolus of 20 mmol/l NaCl immediately before, and then as repetitive 120 ml feedings every 10 min during the first 50 min of exercise. In the other trial they did not ingest fluid (NF) either before or during exercise. The order of testing was in a counter-balanced random sequence. For the first 60 min of exercise mean (+/- SD) VO2 (2.90 +/- 0.39 vs 2.93 +/- 0.38 l/min) and respiratory exchange ratio (RER; 0.95 +/- 0.03 vs 0.94 +/- 0.04) values were similar between F and NF trials. However, weight loss was significantly reduced during F compared to NF (0.16 +/- 0.39 vs 1.30 +/- 0.22 kg; p < 0.005) and high-intensity cycling time to exhaustion was significantly increased (9.8 +/- 3.9 vs 6.8 +/- 3.0 min; p < 0.005). Increased cycling times to exhaustion in the F trial were not associated with any measurable differences in heart rate (HR), body temperature, respiratory gas exchange, leg muscle power over 5 sec, or the degree to which fluid ingestion reduced the level of dehydration within the group. Only the ratings of perceived exertion (RPE) and plasma anti diuretic hormone (ADH) concentrations were significantly increased in the NF trial compared to the F trial.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8002118 TI - Sickle cell trait as a limiting factor for high-level performance in a semi marathon. AB - Of 1506 black males participating in the first Abidjan semi-marathon, 123 subjects with sickle cell trait (SCT) were detected, i.e., 8.7%. Twenty-nine of these subjects with hemoglobin S (HbS) were ranked among the first 332 participants to finish the race, a percentage of 8.2. These percentages did not significantly differ from the prevalence of SCT observed in the general Ivory Coast population (12.0%). Only one subject with SCT was found among the 22 internationally-ranked athletes. The concentration of HbS found in this athlete (37.7%), his mean globular volume (87 fl), and his hemoglobin concentration (13.8 g/100 ml) suggest the coexistence of alpha-thalassemia with SCT. These results indicate that the percentage of SCT individuals participating in a semi-marathon is equal to the prevalence of SCT found in the local population. Furthermore, the general ranking of SCT individuals is comparable to that of non-SCT individuals. Nevertheless, at the level of internationally-ranked performance, no subject with SCT only, was ranked; the one ranked subject with SCT presented an associated alpha thalassemia. We thus hypothesize that SCT may be a limiting factor for high level performance in a semi-marathon and alpha-thalassemia, an enhancing factor for subjects with SCT to succeed in long distance races. PMID- 8002119 TI - The effect of acute hypoxia at low altitude and acute normoxia at high altitude on performance during a 30-s Wingate test in children. AB - The effect of acute hypoxia (FIO2 = 0.137 +/- 0.001) at Low Altitude (LA: Clermont-Ferrand, 330 m) and acute normoxia (FIO2 = 0.306 +/- 0.006) at High Altitude (HA: La Paz, 3600 m) on performance during a 30-s Wingate test has been investigated in prepubertal children (Tanner stage 1). Twenty five boys (LA, n = 10; HA, n = 15) aged from 10.6 to 12.7 years performed two Wingate tests at random: at LA, one in normoxia (ambient air) and one in acute hypoxia and at HA, one in chronic hypoxia (ambient air) and one in acute normoxia. The subjects performed the two tests using the same calibrated cycle ergometer. Peak Power (PP), Mean Power (MP), O2 uptake during the 30 s (VO2) and blood lactate accumulation (delta [L]s) were measured. Compared to normoxia, acute hypoxia at LA did not alter PP (8.0 +/- 1.1 vs 7.9 +/- 1.3 W.kg-1 BW) and MP (6.1 +/- 0.7 vs 6.1 +/- 1.1 W.kg-1 BW). Similarly, compared to chronic hypoxia, acute normoxia at HA did not modify these parameters (PP: 7.4 +/- 1.5 vs 7.3 +/- 1.8; MP: 5.4 +/- 1.2 vs 5.5 +/- 1.1; W.kg-1 BW). VO2 and delta [L]s were neither significantly changed by acute hypoxia at LA (520 +/- 50 vs 550 +/- 60 ml O2; 5.3 +/- 1.7 vs 4.8 +/- 1.7 mmol.l-1) nor by acute normoxia at HA (530 +/- 110 vs 500 +/- 90 ml O2; 3.4 +/- 1.3 vs 3.3 +/- 1.0 mmol.l-1).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8002120 TI - Lipolytic and cardiac responses to various forms of stress in humans. AB - The lipolytic and the cardiac responses to 30 min of two different forms of stress--a standardized mental stress test and submaximal bicycle exercise--were investigated in non-obese healthy subjects. This was done by microdialysis of the extracellular space in the abdominal subcutaneous adipose tissue in order to determine lipolysis and electrocardiographic recordings of the heart rate. Glycerol concentrations (lipolysis index) in venous plasma and in adipose tissue dialysate as well as plasma catecholamines and determinations of the heart rate showed marked increases during mental stress (p < 0.001) and physical exercise (p < 0.001), but the patterns of response differed during the two forms of stress. All parameters rose gradually during exercise and decreased continuously in the post-exercise period. During mental stress, however, all parameters peaked within the first 20 min of stimulation and then remained at the same level until after the stress period, when they gradually declined. The maximal increase of glycerol in plasma and adipose tissue during mental stress correlated with the corresponding increase during exercise (r = 0.50-0.60). Such a relationship was not observed with plasma catecholamines or heart rate (r = 0.02-0.29). The peak level of plasma noradrenaline was an independent regressor for the peak levels of glycerol in plasma and adipose tissue as well as for the peak heart rate during mental stress and physical exercise (partial r from 0.35 to 0.64), while the peak level of adrenaline was a regressor for heart rate only during mental stress (partial r = 0.45), when multiple regression analysis was used.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8002121 TI - Warm-up, stretching and massage diminish harmful effects of eccentric exercise. AB - The effect of a combination of a warm-up, stretching exercises and massage on subjective scores for delayed onset muscle soreness (DOMS) and objective functional and biochemical measures was studied. Fifty people, randomly divided in a treatment and a control group, performed eccentric exercise with the forearm flexors for 30 min. The treatment group additionally performed a warm-up and underwent a stretching protocol before the eccentric exercise and massage afterwards. Functional and biochemical measures were obtained before, and 1, 24, 48, 72 and 96h after exercise. The median values at the five post-exercise time points differed significantly for DOMS measured when the arm was extended (p = 0.043). Significant main effects for treatment were found on the maximal force (p = 0.026), the flexion angle of the elbow (p = 0.014) and the creatine kinase activity in blood (p = 0.006). No time-by-treatment interactions were found. DOMS on pressure, extension angle and myoglobin concentration in blood did not differ between the groups. This combination of a warm-up, stretching and massage reduces some negative effects of eccentric exercise, but the results are inconsistent, since some parameters were significantly affected by the treatment whereas others were not, despite the expected efficacy of a combination of treatments. The objective measures did not yield more unequivocal results than the subjective DOMS scores. PMID- 8002122 TI - Cross-sectional areas of fat and muscle in limbs during growth and middle age. AB - Age changes in the cross-sectional areas (CSAs) of fat and muscle tissues of limbs were investigated by using a B-mode ultrasonic technique for 245 males and 275 females aged 6 to 60 years. Four measurement sites were selected in the right limbs: the forearm, upper arm, lower leg and thigh. In an age span from 13 to 15 years, fat CSA for males decreased, while that for females increased at every site. Fat CSAs for both sexes increased in their thirties, but from then there was no more increase with aging. During early childhood, females had similar growth curves in muscle CSAs to those of males. An apparent sex separation in muscle CSAs took place at 13 years of age and after, the relative gender differences in muscle CSAs became larger with growth in the upper extremity than in the lower one. For both sexes, muscle CSA in every site remained almost constant during middle age. This age change in fat and muscle CSAs of limbs during the period of growth generally resembles that reported previously for total fat and fat free mass, respectively. However, age trend in fat CSAs during middle age, a lack of increase on reaching and after the forties differs from that described by prior studies for fat mass. PMID- 8002123 TI - Relationship between VO2max and the aerobic demand of running in elite distance runners. AB - The purpose of this study was to assess the relationship between VO2max and the aerobic demand of running (VO2submax) in elite distance runners. On at least one occasion, VO2max and VO2submax values were obtained on 22 male subjects (mean age = 27 +/- 2 yrs; mean height = 178.6 +/- 6.8 cm; mean body mass = 64.1 +/- 5.6 kg; mean 10 km run time = 28.89 +/- 1.05 min) training for the 1994 Olympic Trials. Subjects performed 6-min, submaximal level-grade treadmill runs at four speeds (ranging from 4.47 to 5.50 m.s-1) to determine VO2submax. VO2 during each run was calculated by analyzing a 2-min gas sample collected during the last 2 min of running. These values were expressed relative to distance traveled and averaged to derive an overall VO2submax value. Shortly following these submaximal runs, VO2max was measured. When more than one set of VO2submax and VO2max data were available for a particular subject, the average of all tests was used. Results indicated that mean VO2max and VO2submax values were 75.8 +/- 3.4 ml.kg-1.min-1 and 184.6 +/- 8.6 ml.kg-1.km-1, respectively. Correlational analyses also revealed a significant relationship (r = 0.59; p < 0.01) between VO2max and VO2submax. These data suggest that among similarly-performing elite distance runners, a positive relationship exists between VO2max and the aerobic demand of running. PMID- 8002125 TI - Dietary, serum and urine ascorbic acid status in male athletes. AB - The ascorbic acid (AA)-status of 14 marathon runners, 12 soccer players, 9 wrestlers, 9 basketball players and 16 controls was determined. A 7-day food weighed record was kept to quantify the AA-intake. In addition, the AA-serum concentrations and urinary ascorbate excretion were measured. The AA-intake of all 44 athletes (median, 26th-75th percentile) was 180.7 (188-239) mg/d, the serum concentration 70.6 (65.7-80.2 mumol/l) and the urine ascorbate excretion 1531 (391-2934) mumol/g creatine. No significant differences could be observed between the various sport groups, or between the sport groups and controls with respect to absolute (mg/d) and relative (mg/g body weight) AA-intake, serum and urine concentrations. Only a few of the athletes had AA-intake below the RDA or serum- or urine levels smaller than the decision limit. The absolute AA-intake (n = 44) from the 7-day record (r = 0.49, p < 0.0009) and the AA-intake on the last day (1-day) prior to urine collection (r = 0.90, p < 0.0000) correlate moderately/strongly with the urinary excretion. Between AA-intake (7-day) and serum concentration there is a correlation of r = 0.59, p < 0.0000. The AA-status of highly trained athletes does not differ significantly from the control group in spite of intensive daily training. Thus, AA-supplementation beyond the normal daily intake does not appear necessary. PMID- 8002124 TI - Adding polylactate to a glucose polymer solution does not improve endurance. AB - Polylactate (PL), a semi-soluble amino acid/lactate salt, is a newly developed carbohydrate supplement purported to increase endurance. Our purpose was to determine if the addition of PL to a glucose polymer solution (GP) extends exercise time relative to a pure GP solution. In a double blind and random crossover design, 5 subjects exercised twice to exhaustion at 70% of VO2max. During the trials, they consumed GP or a GP/PL mixture at the rate of 0.3 g carbohydrate per kg of body wt in a 7% solution every 20 min until exhaustion. The GP/PL mixture contained 6.25 g GP to 0.75 g PL per 100 ml of water. Mixture composition was critical because PL, as supplied by the manufacturer and under our experimental conditions, produced severe gastro-intestinal efflux in concentrations > or = 2.5%; PL was tolerable in concentrations < or = 0.75%. At 20 min intervals, we measured VO2, respiratory exchange ratio, heart rate, and perceived exertion. At 30 min intervals, we measured serum glucose, insulin, free fatty acids, and glycerol as well as whole blood lactate and pH. We found that the addition of PL to a GP solution had no measurable physiological or performance effects. PMID- 8002127 TI - Disability and rehabilitation in cross-cultural perspective: a view from New Zealand. PMID- 8002126 TI - Suppressed PMA-induced oxidative burst and unimpaired phagocytosis of circulating granulocytes one week after a long endurance exercise. AB - Ten endurance athletes performed two exhaustive intensive endurance exercises (Ex1: 21 +/- 7 min; Ex2: 18 +/- 6 min) on a cycle ergometer at 110% of their individual anaerobic threshold (maximal lactate concentration at Ex1: 9.7 +/- 2.3 mmol.1-1, Ex2: 9.5 +/- 2.2 mmol.l-1). Ex1 was performed two weeks before, Ex2 8 or 9 days after a long endurance competition (duration: 762 +/- 74 min), respectively. At both exercises before, at the 10th, during the last two and 60 minutes after exercise venous blood samples were taken to determine rat and activity of phagocytosis (FITC-conjugated, opsonized E. coli) and oxidative burst (intracellular oxidation of dihydrorhodamine123 to rhodamine123 after induction by phorbol-myristate-acetate) was measured in circulating granulocytes by flow cytometry. Statistical analysis was performed with procedures of ANOVA. Neither at Ex1 nor at Ex2 rate or activity of phagocytosis changed significantly over time, a difference between Ex1 and Ex2 was not observed. In contrast to Ex1, at Ex2 the bactericidal capacity of granulocytes decreased significantly by 37% at the end of exercise. This effect at Ex2 was reversible within the first hour of recovery. The observed transient and partial suppression of the oxydative burst was not accompanied by clinically apparent infections. Therefore, we conclude that the observed in vitro effect is without major clinical importance in healthy subjects. PMID- 8002128 TI - Rehabilitation technology product taxonomy: a conceptual tool for analysing products and extracting demand determinants. AB - This paper proposes and describes a conceptual tool, namely the rehabilitation (assistive) technology (RT) product taxonomy, as a framework for analysing rehabilitation technology products and extracting demand determinants. The ultimate objective of this work is to provide demand and supply-related actors with a meaningful tool for identifying and focusing on specific aspects, which may be directly or indirectly related to existing or new products, so that demand and consumption allocation decisions can be targeted, evaluated and/or predicted. PMID- 8002129 TI - Screening process to discover insured persons in need of rehabilitation. AB - In order to prevent early retirements in Germany, medical rehabilitation measures are implemented among workmen and salaried employees whose fitness for work is jeopardized or diminished. Only around half of those retiring early take advantage of these measures in the last 5 years prior to retirement. To increase the numbers making use of rehabilitation measures, we developed a screening process whereby the pension insurance institutions responsible for the measures are able to identify insured persons in need of rehabilitation and urge them to take part. The screening process comprises two stages: written questioning to determine the probable risk cases by means of predictors of early retirement, and medical clarification of these cases by means of a standardized rehabilitation assessment. The screening process and devices were tested in an experimental trial involving 600 people aged between 45 and 54 insured with a pension insurance institution responsible for workers in the Stuttgart area. Main results were: (1) The screening process was accepted by the insured. Around 70% of the insured took part in the screening. (2) The questionnaire is suitable for pre selection of the probable risk cases that require medical clarification. Given complete answers, 83% of the cases were correctly classified in comparison with the judgement of the pension insurer's physicians. (3) The screening was effective, i.e. it increased the participation of insured persons in need of rehabilitation in rehabilitation measures. Compared with a control random sample, in the experimental trial, 70% more rehabilitation measures were applied for and approved. PMID- 8002130 TI - Comparing the origins and ideologies of the independent living movement and community based rehabilitation. AB - Community-based rehabilitation (CBR) and independent living (IL) differentiate their orientations from traditional rehabilitation models and both place significant emphasis on consumer and community participation. Although the formative structural forces and historical roots of the two rehabilitation approaches are very different, comparison of them is necessary for the following reasons. First, the disabled consumers movement is increasingly involved in international work and has fostered the development of organizations in Southern countries which apply an independent living and consumer-based perspective. It is therefore useful to develop a clear understanding of the cultural and historical background of this movement and its rootedness in the North American experience. Secondly, there has been some discussion of introducing the CBR model into North America. While an attractive concept, it is critical to understand that CBR was developed for a very different context. Most importantly, it grew up in the absence of a fully articulated consumer movement or a fully professionalized and elaborated system of rehabilitation. Expansion of both CBR and IL reflects the emerging dialogue and exchange which is transforming both movements. PMID- 8002131 TI - The identification of continuing education needs for community rehabilitation workers in a rural health district in the Republic of South Africa. AB - Based on the principle that education is a lifelong process, the paper presents the identification of continuing education needs of community rehabilitation workers, who recently completed a 2-year certificate course in a rural health district of the Republic of South Africa. The need for a new cadre of worker in the rehabilitation field, namely a community-rehabilitation worker (CRW), was advocated by WHO in 1981. The CRW works at the community level to address the needs of disabled people, as part of primary health care services. The nominal group technique (NGT) and a focused group discussion was done with the community rehabilitation workers (n = 8) and their supervisors (n = 5), to identify learning needs that should be addressed through a continuing education programme. Focused group discussions involving people with disabilities and their family members (n = 45), from villages where the CRWs work, were carried out to discover their opinions on skills that the community rehabilitation workers still needed. The results show a strong correlation between the needs identified by the three groups, viz, skills in advocacy and public education, social work, community development and organizational development. PMID- 8002132 TI - Coping with epilepsy in Zimbabwe and the Midwest, USA. AB - In this article, the experiences of persons with epilepsy were explored in terms of coping with providing a basis of discussion and training to support groups, particularly in Zimbabwe. Coping mechanisms lay stress upon the individual's control in mastering the disease. It was assumed that a systematic research effort of intra-cultural and cross-cultural sharing of experiences could enhance discussion and training in the support groups. Coping with epilepsy was explored with 37 adults (27 from Zimbabwe and 10 from the Midwest, USA) using open-ended questions in a written questionnaire. Questions aimed to elicit general feelings, experiences and strategies and skills in coping with epilepsy. The questionnaire covered such semantic domains as childhood, education, employment, friendships, relations within the family, and handling of seizures in public places. Coping mechanisms were categorized into two modes, one, adjustment to the disability (palliative), the other adjustment to the environment (problem-solving). In comparing the information between the two groups, some trends can be distinguished which need a larger scale validation. First, palliative skills during childhood in the Zimbabwean group is indicative for early development of personality characteristics and socialization as a result of the illness experiences. A great variety in palliative mechanisms in handling seizures indicates better familiarity with seizures in the Midwestern group. Similarities between the two groups are found in the friendship domain, where palliative coping skills seem to be of no importance, as well as in the domain of intimate relations, where a trend in adherence to medication is observed in both groups. Second, many problem-solving skills are developed in both groups but vary in context. In view of public education and training activities and the enhancement of problem-solving skills, the domain of education for the Zimbabwean group and the domains of friendship with the Midwestern group and the family perhaps deserve more attention. Third, coping skills in the Zimbabwean group tend to be related to the experience of 'being different', while in the Midwestern group 'not being able to doing things' is a major experience. Fourth, in linking coping mechanisms to the cultural environment, two major cultural influences in Zimbabwe stand out as being different from the Midwest, the first being the belief in external control and cause of mental and physical health, and the second, cultural conflict. PMID- 8002133 TI - Effect of home size on the activity of people with a learning disability who move from hospital to community based homes. PMID- 8002134 TI - Return to work for persons with traumatic brain injury and spinal cord injury: three case studies. PMID- 8002135 TI - Cutaneous scars: Part I. PMID- 8002136 TI - Sporotrichosis in man and animal. PMID- 8002137 TI - Systemic therapy for mycoses: changing targets and changing agents. PMID- 8002138 TI - Women in dermatology: a personal view. VIII. PMID- 8002139 TI - Clinical and histopathologic spectrum of pilomatricomas in adults. AB - BACKGROUND: Pilomatricomas are benign cutaneous neoplasms with differentiation toward hair matrix. Although previously reported to occur mostly in children and young adults, Taaffe et al. recently observed a second onset peak in adults and the elderly. METHODS: To study the clinical and histopathologic features of pilomatricomas in adults we analyzed files and histologic sections of all cases of pilomatricomas seen at the Department of Dermatology, University of Graz, Graz, Austria, between January 1980 and December 1990. RESULTS: A total of 118 patients were identified, 58 of whom were > 45 years of age. The clinical features of patients > 45 years of age were generally similar to those of patients < 45 years of age. Differential diagnoses in both groups were also comparable except in some cases of the older study-group where differential diagnoses included basal cell carcinoma, keratoacanthoma, and metastasis. Recurrence of the lesions after simple excision was observed in one patient > 45 years of age. Histopathologically, lesions in both age groups showed similar features except in four lesions of the older patients where "atypical" features were present. The histopathologic differential diagnosis of the lesions with "atypical" features included pilomatrical carcinoma, basal cell carcinoma with matrical differentiation, and matricoma. CONCLUSIONS: Our study reveals the relatively frequent occurrence of pilomatricomas in adults and the elderly. Pilomatricoma should be considered along with other benign and malignant conditions in the clinical differential diagnosis of solitary, firm skin nodules presenting in adults and the elderly, especially on the head and neck. PMID- 8002140 TI - Contact dermatitis due to budesonide: report of five cases and review of the Japanese literature. AB - BACKGROUND: Contact allergy to corticosteroids has recently gained increased attention. METHODS: Five cases of contact dermatitis due to budesonide, a nonhalogenated steroid, are described. The Japanese literature was reviewed for reports on this allergy, and the occurrence due to budesonide was compared with that of other dermocorticosteroids. RESULTS: Budesonide use can cause contact dermatitis. CONCLUSIONS: Although budesonide may be beneficial because of its anti-inflammatory effects, clinicians should be alert to its potential for causing contact dermatitis. PMID- 8002141 TI - Chromoblastomycosis successfully treated with fluconazole. PMID- 8002142 TI - Primary cutaneous coccidioidomycosis treated with itraconazole. PMID- 8002143 TI - Cutaneous metastasis from vulvar adenocarcinoma. PMID- 8002144 TI - Tungiasis--an unusual case of severe infestation. PMID- 8002146 TI - Disk diffusion susceptibility testing of dermatophytes with allylamines. AB - BACKGROUND: Allylamines are a newly developed group of drugs possessing a broad spectrum of activity against a wide range of fungi. With the advent of new antifungal drugs, susceptibility testing of fungi is receiving increased attention as important laboratory procedures for aiding in the selection of appropriate drug therapy. METHODS: In vitro susceptibility testing of 43 clinical isolates of dermatophytes which included Microsporum sp., (18) Trichophyton sp., (23) and Epidermophyton floccosum (2) were carried out against the two allylamine derivatives, naftifine and terbinafine, by agar dilution and disk diffusion methods. RESULTS: Terbinafine was found to be more active minimal inhibitory concentration (MIC range < or = 0.0001-0.1 micrograms/mL), inhibiting 50% (MIC 50) and 90% (MIC 90) of the isolates at 0.01 and 0.1 micrograms/mL, respectively. The MIC 50s and MIC 90s of naftifine were 0.1 micrograms/mL (MIC range 0.001-0.5 micrograms/mL). Both the drugs showed good correlation between the MIC and sizes of zones of inhibition around the disks. Regression analysis was used to measure the degree of correlation between the MIC values and matched averaged zones of inhibition; the correlation coefficients for both terbinafine and naftifine were 0.6841 (P < 0.001) and -0.5455 (P < 0.001), respectively. CONCLUSIONS: The allylamines, naftifine and terbinafine, could be used successfully for susceptibility testing of dermatophytes by the disk diffusion method. With proper standardization of the test conditions, in vitro susceptibility testing of filamentous fungi by disk diffusion would become a useful laboratory procedure in the near future for determining the best drug therapy. PMID- 8002145 TI - Fluconazole versus ketoconazole in the treatment of dermatophytoses and cutaneous candidiasis. PMID- 8002147 TI - In vitro evaluation of griseofulvin, ketoconazole, and itraconazole against various dermatophytes in Singapore. AB - BACKGROUND: Superficial cutaneous fungal infection, principally dermatophytosis, is an extremely common skin disease. Various in vitro test systems have been developed in recent years to determine the antifungal activity of various drugs. The minimum inhibitory concentration (MIC) obtained may give an indication of the in vivo potency of the drugs. METHODS: One hundred patients (69 men and 31 women) with a clinical diagnosis of dermatophytosis were entered into the study. Direct microscopy and culture were done on all patients. The MICS were determined using the broth dilution method. RESULTS: The age range was 1-76 years. The most common diagnosis was tinea corporis (36%), followed by tinea cruris (22%), and tinea pedis (19%). The most common fungus isolated was T. rubrum (58%), followed by E. floccosum (14%), and T. mentagrophytes (10%). The majority of the isolates was sensitive to the three drugs tested (griseofulvin, ketoconazole, and itraconazole). Of the isolates, 82% were sensitive to griseofulvin, 78% to ketoconazole, and 81% to itraconazole, all at a concentration of < 0.25 micrograms/mL. For T. rubrum, there were four isolates that had an MIC of > or = 64 micrograms/mL to griseofulvin, seven isolates and nine isolates with an MIC > or = 64 micrograms/mL to ketoconazole and itraconazole, respectively. T. interdigitale was relatively resistant to the three drugs in vitro with four of seven isolates having an MIC > or = 4 micrograms/mL with griseofulvin, one of seven isolate with an MIC > or = 64 micrograms/mL with ketoconazole, and three of seven isolates with an MIC > or = 32 micrograms/mL with itraconazole. CONCLUSIONS: The in vitro antifungal activity of griseofulvin, ketoconazole, and itraconazole are similar against dermatophytes in Singapore. Griseofulvin may be given as the first-line drug for treating such infections in Singapore. PMID- 8002148 TI - Treatment of superficial mycoses in the tropics: Whitfield's ointment versus clotrimazole. AB - BACKGROUND: In tropical primary health care, essential drugs should be safe, effective, and as inexpensive as possible. To treat the very common dermatophyte infections of the skin, one may use inexpensive Whitfield's preparations, more expensive topical imidazole derivatives, or extremely expensive oral antifungals. Because a cream base is felt to be more appropriate than an ointment in tropical conditions, we wanted to compare the effectiveness of Whitfield's cream and a topical imidazole derivative in field conditions in the tropics. METHODS: A double-blind trial was performed involving 153 patients with a dermatophyte infection of the skin in Karonga District, Northern Malawi, including 25 patients who were HIV-1-seropositive, comparing Whitfield's cream with clotrimazole cream. RESULTS: 75 patients were treated with Whitfield's cream and 78 with clotrimazole cream for a period of 6 weeks. Cure rates ranged from 80% to over 90% depending on the definition of cure. If positive cultures after treatment were used as criterion for treatment failure, six were found in each treatment group. One in each treatment failure group was an HIV-1-seropositive patient. CONCLUSIONS: The great majority of patients in the tropics with a dermatophyte infection of the skin can be cured with a topical antimycotic preparation and do not need expensive oral therapy. This also proved to be valid for HIV-1-seropositive patients. Whitfield's cream and clotrimazole cream are both very effective. The lower cost makes Whitfield's cream the treatment of choice in dermatophyte infections of the skin in tropical primary health care. PMID- 8002149 TI - Itraconazole versus griseofulvin in the treatment of tinea capitis: a double blind randomized study in children. AB - BACKGROUND: Tinea capitis is a fungal infection in which topical therapy is often unsuccessful. Griseofulvin has been considered to be a first-line therapy. Other antifungal agents are the azole derivatives. Among these, itraconazole was compared with griseofulvin in children in a double-blind study. PATIENTS AND METHODS: Thirty-four children and one adult with clinical signs and symptoms of tinea capitis and with positive culture and microscopy for dermatophytes have been included in a double-blind comparison between itraconazole, 100 mg daily, and ultramicronized griseofulvin, 500 mg daily. Both drugs were given for 6 consecutive weeks. The final evaluation was made 8 weeks after the end of treatment to allow the hairs to regrow. Seventeen itraconazole- and 15 griseofulvin-treated patients received the complete 6-week treatment course. Fifteen of these 17 itraconazole patients and 14 of the 15 griseofulvin patients had infections caused by Microsporum canis. Fifteen of 17 patients were cured by itraconazole (88%) and 15 of 17 patients by griseofulvin (88%). One of the patients who discontinued griseofulvin therapy after 4 weeks was clinically and mycologically cured. Two of the original 17 griseofulvin patients discontinued therapy because of vomiting. None of the itraconazole-treated children experienced side effects. CONCLUSIONS: Itraconazole is the first azole derivate that matches griseofulvin for the treatment of tinea capitis in children. The drug also appears to be better tolerated than griseofulvin. PMID- 8002150 TI - Aquagenic pruritus response to the exogenous nitric oxide donor, transdermal nitroglycerin. PMID- 8002151 TI - Chemoimmunotherapy: its relevance in contemporary context. PMID- 8002152 TI - Cutaneous manifestations of diabetes mellitus. PMID- 8002153 TI - Verrucous carcinoma of the oral cavity. PMID- 8002154 TI - Chronic wounds: myths about decubitus ulcers. PMID- 8002155 TI - Women in dermatology--a personal view. VII. PMID- 8002156 TI - Dermatoglyphics in Darier's disease. AB - BACKGROUND: Darier's disease is an acantholytic dyskeratotic genodermatosis with autosomal dominant inheritance. A predictive diagnostic marker for this disorder would be beneficial because of the relatively late onset and the large number of sporadic cases of the disease. The dermatoglyphic features of patients with Darier's disease were examined to determine whether they have a common pattern. METHODS: Ink prints of fingers and palms obtained from 11 patients of both sexes with sporadic and familial Darier's disease were analyzed and compared with those of normal subjects. RESULTS: No significant quantitative or qualitative differences were found between the dermatoglyphic features of our patients and those of a healthy population, except for punctate interruptions of the skin ridges that indicate pitting, a well-known manifestation of Darier's disease. CONCLUSIONS: These results refute the conclusions of a previous publication claiming that there is a common characteristic dermatoglyphic feature in patients with this dermatosis. PMID- 8002157 TI - Cutaneous involvement in chronic myelomonocytic leukemia. AB - BACKGROUND: Chronic myelomonocytic leukemia has been associated with various nonspecific cutaneous manifestations. Rarely has the leukemia been reported to directly affect the skin. METHODS: This case documents the progression of a patient who ultimately developed chronic myelomonocytic leukemia, by clinical examination, hematologic parameters, dermatopathology, and bone marrow pathology. RESULTS: The skin showed nonspecific cutaneous involvement, progressing to specific leukemic lesions parallel with increasing systemic and hematologic involvement. CONCLUSIONS: Chronic myelomonocytic leukemia can manifest with lesions of leukemia cutis. The possibility of nonspecific cutaneous involvement in the preleukemic phase exists. PMID- 8002158 TI - Prevalence of thyroid diseases in patients with alopecia areata. AB - BACKGROUND: The prevalence of thyroid disease in patients with alopecia areata previously reported varied from 0 to 28%. These thyroid diseases, include Hashimoto's thyroiditis, Graves' disease, simple goiter, and others. METHODS: The prevalence of thyroid diseases was determined in 152 consecutive patients with alopecia areata who presented to the dermatology clinic. A complete history was taken and a physical examination was performed. Thyroxine, triiodothyronine, thyroid-stimulating hormone, and microsomal antibody levels were measured in every patient. The control group consisted of 152 age- and sex-matched volunteers who had skin diseases other than alopecia areata or autoimmune disorders. RESULTS: Among 152 patients, age 10-59 years, four cases (2.6%) had a small simple goiter. Microsomal antibodies were detected in seven other patients (4.6%) with titers ranging from 1:100 to 1:1600. None of these seven patients had signs or symptoms of thyroid disease. Five cases (3.3%) of the control group had positive microsomal antibody tests with titers ranging from 1:100 to 1:400. The prevalence of positive microsomal antibodies in the alopecia areata group was not statistically different from the control group (chi 2 = 0.347, DF = 1, P = 0.5558). CONCLUSIONS: Among 152 patients with alopecia areata, 4.6% of patients had microsomal antibodies and 2.6% had a small simple goiter. Thus the prevalence of thyroid disease among these patients was 7.2%. The prevalence of positive microsomal antibodies in 4.6% of the patients was not statistically different from that of the control group. PMID- 8002159 TI - Diffuse intraepidermal deposition of immunoreactants on direct immunofluorescence: a clue to the early diagnosis of epidermal necrolysis. AB - BACKGROUND: Toxic epidermal necrolysis is a distinctive disorder that is readily identified clinically and histologically in advanced cases. Early on, however, toxic epidermal necrolysis may be difficult to identify. Some consider fixed drug eruption a limited form of toxic epidermal necrolysis. METHODS: Direct immunofluorescence was performed on biopsy material of erythematous skin lesions. RESULTS: Diffuse deposition of immunoreactants in the midmalpighian layer was noted. This finding has not been encountered in other disorders studied in our immunopathology laboratory. CONCLUSIONS: Diffuse immunoreactant deposition in the mid-epidermis should suggest a diagnosis of epidermal necrolysis either from toxic epidermal necrolysis or fixed drug eruption. Additional cases will need to be assessed to document the usefulness of this pattern for prospective diagnosis. PMID- 8002160 TI - Verrucous carcinoma of the lip originating on the vermilion border. PMID- 8002162 TI - Multiple angiokeratomas with zosteriform distribution in two sisters. PMID- 8002161 TI - Erythema elevatum diutinum. PMID- 8002163 TI - Erythromelanosis follicularis faciei et colli. PMID- 8002164 TI - Lichen planus subtropicus: direct immunofluorescence findings and therapeutic response to hydroxychloroquine. PMID- 8002165 TI - Progressive systemic sclerosis associated with cutaneous amyloidosis. PMID- 8002166 TI - Eccrine angiomatous hamartoma. PMID- 8002167 TI - Mycosis fungoides with signet-ring cells and monoclonal gammopathy. PMID- 8002168 TI - Trends in medical education. PMID- 8002169 TI - Reconstruction of the nose utilizing a bilobed flap. AB - BACKGROUND: Defects of the distal nose are particularly challenging to reconstruct because of this area's unique texture, lack of elasticity, and possible distortion of the alar rim. The bilobed flap has been criticized for having a high incidence of "trapdooring," flap necrosis, dog ears, and prominent suture lines. METHODS: Patients who underwent bilobed flap repairs of the distal nose (n = 171) were reviewed for complications and cosmetic results. The modifications from the traditional design include minimizing the angle of transposition between lobes, thinning of the flap, basing the pedicle on the lateral aspect of the nose, and creating the lobes of the flap to be of equal diameter to the defect. RESULTS: There was a 3% incidence of infection, 7% incidence of partial flap necrosis, and 5% incidence of "trapdooring" and contour distortion. Color match and contour were excellent for all other patients. CONCLUSIONS: The modified bilobed flap is an excellent choice for reconstruction of defects of the lower nose because of the good skin match and low incidence of complications. PMID- 8002170 TI - Ultrastructural study of hyaluronic acid before and after the use of a pulsed electromagnetic field, electrorydesis, in the treatment of wrinkles. AB - BACKGROUND: Treatment of wrinkles has become an increasing problem for dermatologists. Hyaluronic acid is a component of the family of glycosaminoglycans (GAGS, substances known for their property of retaining water), that significantly decreases with aging and in wrinkles. A new technique that uses a specific pulsed electromagnetic field, electrorydesis, has been introduced in the treatment of wrinkles associated with aging. The treatment is based on the reported in vitro effects of specific electromagnetic fields on fibroblast cultures (e.g., an increase in DNA synthesis and in the production of collagen and presumably also of GAGS). METHODS: The in vivo effects of the electromagnetic field on aged skin (3 subjects aged 50, 56 and 60 years), with particular focus on the ultrastructural modifications and GAGS amount before and after the treatment, were evaluated by electron microscope. RESULTS: The ultrastructural study (tissue stained with alcian blue) showed after treatment a significant increase (p < 0.005) of the electron-dense granules (corresponding to hyaluronic acid), located in collagen elastic fibers, and in the soluble matrix. This presumably leads to subsequent edema that was clinically evident after the treatment. CONCLUSIONS: These data suggest that the increased levels of GAGS and the subsequent edema of the dermis could explain at least in part the clinical changes observed after electrorydesis treatment (e.g., swelling and "disappearance" of the wrinkle). PMID- 8002171 TI - Beethoven: medicine, music, and myths. PMID- 8002173 TI - Varicella, Koebner phenomenon, and psoriasis. PMID- 8002172 TI - Successful treatment of systemic amyloidosis by combination chemotherapy and plasmapheresis. Effect on plasma IL6 and serum amyloid protein A. PMID- 8002174 TI - Pattern of skin diseases in the Leh-Ladakh region of India. PMID- 8002175 TI - Painful tufted angioma precipitated by trauma. PMID- 8002176 TI - Adult xanthogranulomatosis with an unusual clinical appearance. PMID- 8002177 TI - Forced movements of population and health hazards in tropical Africa. AB - Significant interactions between disease and population mobility have been demonstrated in tropical Africa in recent decades. Problems arising are greater than in the past. During the last two decades forced movements have become important. These are associated with refugees, coerced resettlement and victims of environmental catastrophe. The health hazards associated with them are reviewed from medical and social science literature for North East Africa (refugees and resettlement) and for West Africa (pastoralists affected by drought). Political, social and economic settings are of importance but tend to receive only limited attention. There is need for more social science input in studying and ameliorating problems arising from health hazards associated with and exacerbated by forced movements of population. PMID- 8002178 TI - Statistical modelling and prediction of lung cancer mortality in the Czech and Slovak Republics, 1960-1999. AB - BACKGROUND: The aim of the study was to analyse the pattern of lung cancer mortality from 1960 to 1989 and to predict lung cancer mortality for 1990-1999 for males and females aged > or = 30 years in the Czech and Slovak Republics. METHOD: The mortality pattern of lung cancer was examined and predicted using republic-age-period-cohort models. RESULTS: Trends in lung cancer mortality were upward for both sexes over the study period. In the early 1960s, lung cancer mortality in Slovak males was much lower than that in Czech males, but since the late 1960s lung cancer mortality in males increased more rapidly in Slovakia than in the Czech Republic. It was predicted that mortality due to lung cancer in Slovak males would exceed that in Czech males during the last 5 years of the 20th century. Slovak female lung cancer mortality was lower than that for Czech females throughout the study period, and the trends in both republics were similar. PMID- 8002179 TI - No improvement in survival from melanoma diagnosed from 1973 to 1984. AB - BACKGROUND: While the incidence and mortality of melanoma has increased dramatically during the last few decades, survival rates, based on the case fatality ratio, have apparently improved. Efforts at early detection have probably been effective in the discovery of lesions at a curable stage. However, the effects of lead-time bias need to be accounted for in order to understand the contribution of early detection to the increased incidence. This can best be done by appropriately controlling for depth of the tumour or a surrogate of depth, at diagnosis. METHODS: A survival analysis was conducted for 3197 Connecticut residents newly diagnosed with invasive melanoma between 1973 and 1984. Five prognostic variables were evaluated: sex, age at diagnosis, anatomical site, histological type, and year of diagnosis. RESULTS: As expected, women and the young had better survival than men and the elderly. Melanomas located on the trunk had poorer prognosis than those on other sites. The survival experience by histological type was significantly different; lentigo maligna melanoma and superficial spreading melanoma had the best survival and nodular melanomas the poorest, while 'other' and unclassifiable melanomas had intermediate survival. When survival by period of diagnosis was controlled by other variables, which included surrogates for disease stage, there was no improvement in survival over time. CONCLUSION: These data do not imply that early diagnosis and treatment are ineffective; rather, that within stages of disease, survival improvements did not occur during the period 1973-1984. PMID- 8002180 TI - Is Trichomonas vaginalis a cause of cervical neoplasia? Results from a combined analysis of 24 studies. AB - BACKGROUND: We conducted this combined analysis of available data from studies with information on this issue to clarify the association between Trichomonas vaginalis infection and cervical neoplasia. METHODS: We performed MEDLINE searches (1966-1993) using the key words and phrases 'trichomonas vaginitis' and 'neoplasms, cervix' for articles published in English, and searched citations of the articles obtained from MEDLINE: A total of 24 articles (two cohort studies and 22 case-control) were included in this data analysis. In the analysis, the studies were evaluated for heterogeneity using Breslow-Day tests for homogeneity of the odds ratios and of rate ratios. If the odds ratios from studies are heterogeneous, it is not appropriate to combine them using the Mantel-Haenszel method. Also, publication bias was evaluated by assessing the association between the observed effect size and the variance of the effect size using a rank correlation test. RESULTS: The combined summary relative risk for the two cohort studies was 1.93 (95% confidence interval: 1.22-2.65) indicating an approximate doubling of the risk of cervical neoplasia in the presence of T. vaginalis infection. The attributable risks among exposed subjects and among the source population were 47.4% and 2.1% respectively. Results of the 22 retrospective studies were much less consistent. However, most of them demonstrated a significant positive association. CONCLUSIONS: This combined analysis suggests that there is an association between T. vaginalis and the risk of cervical neoplasia, but that such infections account for only 2% of cervical neoplasia. PMID- 8002181 TI - Parity in relation to mortality and cancer incidence: a prospective study of Norwegian women. AB - BACKGROUND: Few prospective studies relating childbearing to total and cause specific mortality and cancer incidence have been published. The purpose of this paper was to examine these relations in a large cohort of Norwegian women. METHODS: Information on reproductive factors was obtained through interviews with 63,090 women. All deaths and cancer cases during follow-up, 1961-1980, were obtained by linkage to the files at the Central Bureau of Statistics and the Cancer Registry of Norway, respectively. Associations with parity were assessed by stratified logistic regression. RESULTS: For cerebrovascular and ischaemic heart disease, moderate but highly significant positive trends of increasing mortality with increasing parity were observed in the older part of the cohort. Deaths from diseases of the respiratory system and suicide were most common among nulliparous women. Inverse associations with parity were observed for cancers of the breast, corpus uteri and ovaries as well as for melanoma and non-melanoma skin cancers. Positive associations were observed for cancer of the cervix uteri in all age groups, for cancer of the respiratory system among older women and for pancreatic cancer and multiple myelomas in the younger part of the cohort. The results gave no support to previous reports of positive associations with cancer of the liver or gallbladder. CONCLUSIONS: The study supports evidence of an increased risk of ischaemic heart disease in multiparous women, which had been observed previously in three smaller prospective studies. It confirms earlier observations of low risks of cancer of the breast, corpus uteri and ovaries in women with high parity. PMID- 8002182 TI - Myocardial infarction case-fatality gradient in three French regions: the influence of acute coronary care. AB - The objective of this study was to evaluate the influence of acute coronary care on the myocardial infarction (MI) case-fatality gradient observed in three French regions. In 1989, a total of 813 hospitalized events of premature MI, occurring in men and women aged 25-64, were registered in three WHO-MONICA sites established in Lille (North of France), Strasbourg (East of France) and Toulouse (South of France). The case-fatality rates observed 28 days after the onset of the MI, were 30.6% in Lille, 17.5% in Strasbourg and 9.9% in Toulouse (P < 0.0001). We compared the management of events and the use of cardiovascular therapies in these centres before admission to hospital, during the stay and on discharge from hospital. Differences were observed between the three centres in the use of medical treatments: in Strasbourg, aspirin and antiplatelet agents were prescribed 15% less frequently, (P < 0.0001) while diuretics were prescribed twice as often as in Toulouse (P < 0.0001). Thrombolytic agents (P < 0.01) and invasive techniques (coronary angiography, coronary angioplasty and coronary bypass surgery) (P < 0.0001) were more widely used in Toulouse compared with the two other centres. Lille might have a higher rate of coronary case fatality than Strasbourg and Toulouse because of a series of cumulative characteristics. The disease presented in a more serious form: more frequent electrocardiographic changes in anterior leads (P < 0.02), higher percentage of use of inotropic drugs in association with diuretic agents (P < 0.04), and longer duration of stay in intensive care units (P < 0.0001). However, when case-fatality rates were adjusted for all these variables in a multivariate model, the rate remained significantly higher in Lille than in the two other centres (P < 0.0001), as suggested by the odds ratio (3.27, 95% confidence interval: 1.69-6.32). In conclusion, the influence of acute coronary care on the MI case-fatality gradient observed between the North and South of France is very weak. PMID- 8002184 TI - The relationship of dietary animal protein and electrolytes to blood pressure: a study on three Chinese populations. AB - The relationship of diet to blood pressure was studied in a total of 705 men and women aged 40-59 from three Chinese population samples having different mean blood pressure and dietary sodium and animal protein intake. Two groups were farmers from Shanxi in northern China, and Guangxi in southern China, and the third were fishermen from Zhejiang, eastern China. Three 24-hour dietary recalls were done for each participant. Serum and overnight urine amino acids were measured in random subsamples. Determination of electrolytes in three 24-hour urine specimens was done in an additional sample of 59 men in each population. Results of multiple or stepwise regression showed: 1) in the pooled group, individual intake of sodium was positively associated with systolic blood pressure; 2) when stratifying by median calcium intake, a positive association of dietary sodium or sodium/potassium was found only in the group with calcium intake lower than the median; 3) daily intake of animal protein, urinary sulphate and certain serum and urine amino acids formed from protein metabolism, were inversely associated with blood pressure. PMID- 8002183 TI - Blood pressure tracking in Korean schoolchildren. AB - BACKGROUND: Many studies have examined the blood pressure tracking among children and adolescents, but the results have been mixed. This study examined blood pressure tracking in 304 Korean school children following them for 5 years from age 6 to 11. METHODS: In addition to the examination of relative ranking, in percentile groups, of blood pressure and time-lag correlation analysis, we used the McMahan's tracking index, tau (tau), which indicates the proportion of variation attributable to tracking apart from the natural growth (increase) component. RESULTS: There was strong evidence for tracking during the pre-teen years, particularly when it was analysed using McMahan's tracking index. Tau for systolic blood pressure was 0.877 (+/- 0.028) in males and 0.792 (+/- 0.044) in females. For diastolic blood pressure tau was found to be 0.924 (+/- 0.070) in males and 0.762 (+/- 0.075) in females. CONCLUSIONS: This study supported the existence of blood pressure tracking in children, but data were insufficient to examine the effect of puberty on tracking. The need for further research is emphasized with the aim of incorporating biological and behavioural factors and targeting preventive intervention. PMID- 8002185 TI - Adequacy of a single visit for classification of hypertensive status in a Nigerian civil servant population. AB - BACKGROUND: Concern has been expressed regarding the adequacy of classifying individuals as hypertensive based upon a single blood pressure determination and/or the average of readings taken at a single visit and the appropriateness of these determinations in cross-cultural comparisons of rates of hypertension. METHODS: This analysis investigated the potential classification variability by comparing hypertensive status determined by 1) a single reading, 2) an average of the second and third determination at the first visit, and 3) an average of the second and third determinations obtained at each of three visits according to a standardized protocol. Kappa statistic, sensitivity and specificity were calculated to assess the agreement of hypertension classification for 804 subjects in the Health Survey in Nigerian Civil Servants, Benin City, 1992. Data were also compared to other published studies for variability in hypertension classification with repeated blood pressure determinations. RESULTS: Good to excellent agreement was observed for the entire population between the single blood pressure determination, the average of the first visit, and the average of three visits. Sensitivity and specificity measures were also acceptable for the entire population. Further analysis by sex and staff status (a measure of socioeconomic status) found no apparent distinctions between the groups. CONCLUSION: Contrasting the data with other published studies, conducted in both developed and developing countries, we note no greater variability in repeated blood pressure measurements, and conclude that the average of blood pressure determinations at a single visit in this working urban population is adequate for determining hypertensive status for comparisons with hypertension rates in Westernized populations. PMID- 8002186 TI - Mortality among Icelandic seamen. AB - BACKGROUND: The aim of this cohort study was to evaluate the mortality of Icelandic seamen with particular reference to cancer deaths. SUBJECTS: In all 27,884 seamen, both fishermen and sailors of the merchant fleet, who had been members of a pension fund between 1958 and 1986 were followed-up. RESULTS: Most standardized mortality ratios (SMR) were greater than 1:1.26 for all causes, 1.13 for all malignant neoplasms, 1.80 for liver cancer, 1.19 for stomach cancer, 1.56 for lung cancer, and 1.21 for kidney cancer. The highest SMR was found for unknown causes, 3.16. There was no 'healthy worker effect'. For most causes of death latency time and mortality were strongly correlated. When analysing the relation between duration of employment and mortality a correlation was found for all-causes and for stomach cancer; however, this was not statistically significant. CONCLUSION: Seamen have an unusual mortality pattern and the excess for unknown causes is a rare finding indicating a peculiar situation for this group. The excess of stomach and lung cancer was high but it was not convincingly related to duration of employment and thus a relationship to occupation cannot be confirmed. PMID- 8002187 TI - Mortality among seamen with special reference to work on tankers. AB - BACKGROUND: Several studies demonstrate a high mortality among seamen but this has not been related to different types of work on board. This study examined a possible relationship between work on tankers and mortality. Tankers differ from other ships by carrying different types of oil, oil products and other chemicals. METHODS: Mortality was studied in 1687 men who were captains and mates during the period 1970-1987, and were registered by a Norwegian census in 1970. The data were linked to the Norwegian Register of Death Certificates. In all 181 deaths were found. Each case was age-matched at time of death to three individuals from the rest of the population alive at this date. Information about the seamen's work on different ships was obtained for cases and controls. The data were analysed using multivariate conditional logistic regression. RESULTS: Seamen working on tankers had a higher mortality rate ratio (RR = 2.43, 95% confidence interval [CI]: 1.65-3.60) than seamen who had not been working on tankers. The increased risk was especially related to death from cancer and from accidents, while no significantly increased mortality due to cardiovascular diseases was found. Employment as a mate on tankers showed the highest all-causes risk of death (RR = 3.14, 95% CI: 2.04-4.82) as well as for cancer (RR = 4.24, 95% CI: 2.02-8.88) and accidents (RR = 5.85, 95% CI: 1.66-20.60). Employment as a captain on tankers showed no significantly increased mortality. CONCLUSION: Exposure to chemicals on tankers may be related to the increased mortality, as this is the major difference between tankers and other ships and mates are exposed to chemical agents, while captains are not. PMID- 8002188 TI - International variation in the size of mortality differences associated with occupational status. AB - BACKGROUND: Previous international comparisons on the size of mortality differences associated with occupational status have relied on inequality indices with one or more limitations. This study reassesses the international pattern of inequalities in mortality using an inequality index devised recently. METHODS: Data on mortality by social class were obtained from longitudinal studies from seven countries. The data referred to men aged 35-64 years. The follow-up period was approximately 1971-1981. The size of mortality differences associated with occupational status was measured using a modification of the Relative Index of Inequality. RESULTS: The smallest inequalities in mortality are observed for Norway and Denmark. Larger inequalities are observed for Sweden (compared to Norway circa 1.5 times as large), England and Wales (2 times), Finland (4-5 times) and France (6-8 times). Inequalities in a Dutch city, Rotterdam, are as large as in Danish and Swedish cities, and smaller than in Finnish and French cities. Results of sensitivity analyses suggest that probably only a small part of this international pattern can be attributed to differences between countries with respect to occupational classification. CONCLUSIONS: The results of most previous international comparisons agree with the general pattern observed here. This simultaneous comparison of various countries shows that the frequently cited difference between Sweden, and England and Wales is small when viewed in a wider international context. PMID- 8002189 TI - Implications of Russian immigration on mortality patterns in Israel. AB - BACKGROUND: Many immigrants from the former USSR arrived in Israel during the period 1989 to 1992 and now comprise 10% of the Israeli population. They are expected to cause a change in the health profile of the country due to their different patterns of disease and an analysis was undertaken to predict these expected changes. METHOD: Official mortality statistics from Israel and the USSR were compared for differences in major causes of death. Russian mortality rates were then incorporated into a calculation taking into account the total size of the Israeli population and the relative size of the immigrant population to give the expected overall age-adjusted mortality in Israel following the wave of immigration. RESULTS: Reported mortality rates in the European republics of the former USSR were found to be higher, by about 40%, than mortality rates in Israel. Cardiovascular diseases (40%) and cancer (20%) were found to contribute equally to male mortality in Israel and the USSR, but cardiovascular diseases were more important in females in the USSR (65% versus 44% in Israel). Cerebrovascular disease was three times more common as a cause of death in the USSR than in Israel, in both sexes. Cancer, though similar in overall rate, was differently distributed in the two countries with lung and stomach cancer predominating and causing much higher mortality in the former USSR. Projections from these observations showed an expected immediate increase in mortality of 6% in males and 4.4% in females, assuming the mortality patterns reported are valid for Russian immigrants to Israel. CONCLUSION: Massive immigration to a country has the potential to significantly affect the overall health picture of the host country. Therefore, an evaluation of the health status and health-related habits of the immigrant population is warranted to target areas requiring intervention in order to both protect the host country and to facilitate assimilation. PMID- 8002190 TI - Daily morbidity records: recall and reliability. AB - Methodological issues concerning the collection and analysis of daily morbidity data in community studies in developing countries are discussed. The effects of recall period and inter-observer variation on symptom prevalence are considered in the context of a longitudinal study in The Gambia, in which prevalence fell by about half over 1-week's recall. In the same study, many infant-days were recorded separately on two occasions, allowing an assessment of reliability in this type of morbidity diary data. The implications of these findings both in terms of data quality and cost-effectiveness are discussed, with the conclusion that weekly interviews examining the previous week's morbidity on a day-by-day basis are operationally optimal. PMID- 8002191 TI - The relation between psychosocial job strain, and preterm delivery and low birthweight for gestational age. AB - BACKGROUND: The aim of this cohort study was to evaluate the relationship between psychosocial job demands and job control during pregnancy and risk of small-for gestational age (SGA) and preterm delivery. METHODS: We studied 8711 Danish women with singleton pregnancies between 1989 and 1991. Information about medical and obstetric history, general psychosocial and lifestyle factors and occupational exposures were collected at 16 weeks gestation. The analyses were restricted to 3503 respondents who worked at least 30 hours per week during the first trimester. The women's scores on both the job demand and job control questionnaire were initially dichotomized at the median score, and combined into four exposure categories: relaxed jobs (low demands and high control), active jobs (high demands and high control), passive jobs (low demands and low control), and high-strain jobs (high demands and low control). RESULTS: After adjustment for confounders, women with relaxed jobs had the lowest risk of SGA and preterm delivery. Compared to this group the odds ratio (OR) for SGA delivery among women with passive jobs was 1.3 (95% confidence interval [CI]: 0.9-1.9), with high strain jobs 1.1 (95% CI: 0.7-1.6), and with active jobs 1.1 (95% CI: 0.8-1.7). Compared to women with relaxed jobs, the OR for preterm delivery among women with passive jobs was 1.4 (95% CI: 0.8-2.3), high-strain jobs 1.3 (95% CI: 0.7-2.2) and active jobs 1.2 (95% CI: 0.7-2.2). All risks were consistently increased in women with low job control. The risks were higher for preterm than for SGA deliveries. However, none of the findings were statistically significant. CONCLUSIONS: The influence of work-related psychosocial strain on the risk of SGA and preterm delivery seems to be small in countries with highly developed social support systems and few other work-related hazards. PMID- 8002192 TI - Prevalence of childhood asthma across Canada. AB - BACKGROUND: A large cross-sectional study provided an opportunity to estimate the prevalence of childhood asthma in several regions across Canada. METHODS: In 1988, approximately 18,000 questionnaires were distributed to the families of 5-8 year old children in 30 communities from the following six regions across Canada: the interior of British Columbia, southeastern Saskatchewan, southwestern Ontario, the central region of Ontario, southern Quebec, and the Maritimes (Nova Scotia and Prince Edward Island). These communities were free of point-source air pollutants and selected to represent a range of ambient sulphate concentrations. In all 14,948 questionnaires were returned representing an 83% response rate. RESULTS: Currently present, physician-diagnosed asthma was reported for 4.7% of children by their parents. Persistent wheezing was reported for 13% and persistent cough for 5.9%. Asthma was most common in the two Maritime provinces (7.4%), and least common in British Columbia (3.3%) and Quebec (3.4%). Similar regional differences were seen for persistent cough, persistent wheeze, and also hospital separation rates for asthma which were approximately 800 per 100,000 for the Maritimes and 396 per 100,000 for British Columbia. Differences persisted despite adjustments for several host and environmental (indoor and outdoor) characteristics. CONCLUSIONS: The east coast of Canada may be an endemic area of asthma in Canada. If confirmed by objective measures of asthma, a detailed aetiologic investigation could enhance understanding of this phenomenon and the major environmental determinants of asthma morbidity in general. PMID- 8002193 TI - Determinants of stunting and recovery from stunting in northwest Uganda. AB - BACKGROUND: Socioeconomic deprivation is associated with unhealthy living conditions and insufficient nutrient intake which affect linear growth. This study investigates the major risk factors which influence stunting in Northwest Uganda, the age range at which growth failure is more likely to occur, and the age at which chances of recovery are higher. METHODS: In February-March 1987, 1072 children < 5 years, were selected from 30 villages in Arua district (Northwest Uganda) and included in a longitudinal study. The children were measured for length and height; household socioeconomic and environmental variables were collected in order to assess risk factors for the future development of stunting. Two years after baseline, the height of the children was measured again. RESULTS: Children who were < 29 months old at baseline were at higher risk for linear growth faltering in the following 2 years; income, mother's education and presence of stunting at baseline were significant predictors of stunting. However, being stunted at age < 6 months or between 54 and 59 months old carried the same risk of remaining stunted after 2 years, and the probability of recovering from stunting was the same in every age group. CONCLUSIONS: These results suggest that, in this population, linear growth is influenced by environmental factors. It is a dynamic process continuing beyond the first 2-3 years of life, and the probability of catching up is very similar across all age groups < 5 years old. Recovery from stunting is more associated with mother's education than with income. PMID- 8002194 TI - Validity of individual portion size estimates in a food frequency questionnaire. AB - BACKGROUND: Dietary surveys often rely upon subjects' ability to estimate their portion sizes instead of weighing them, but information on the validity of such estimates is lacking. This study investigated the validity of estimated portion sizes from a self-administered food frequency questionnaire including photos. METHODS: Validity was evaluated by comparison with portion sizes from 14-day weighed food records. Eight sets of photos were included in the study (three meat dishes, one fish dish, three vegetables, potatoes), each set with four options. Subjects (59 men, 85 women) were 40-64 years. RESULTS: The majority of subjects (85-95%) selected the most correct photo or a neighbouring photo. However, regression analyses showed that the relationship between the estimated and the measured portion sizes was relatively weak for most of the foods tested, and correlations were only significant for three of the eight foods. This apparent contradiction was partly due to the pattern of the error: subjects selecting small portions had underestimated their actual portions while subjects selecting large portions had overestimated them. This error pattern could not be explained by the theoretical error resulting from the use of four discrete portion sizes instead of continuous weights, neither was it a simple consequence of the unidirectional errors at the extreme ends. Actual portion sizes varied from day to day, with intra-individual coefficients of variation of 34-40%. CONCLUSIONS: The photos used in the present study were of limited value for ranking individuals correctly according to their actual portion sizes. Whether this is a common feature of photos used in food frequency questionnaires remains to be answered. PMID- 8002195 TI - Intravenous administration among heroin users having treatment in Spain. AB - BACKGROUND: Of critical importance to AIDS control in Spain is the analysis of geographical variation and trend over time in the prevalence of intravenous administration in heroin users, as well as the factors associated with the use of this route. METHODS: We carried out a cross-sectional study of 27,655 people admitted to outpatient treatment for heroin dependence in 15 of the 17 Autonomous Communities of Spain during 1991, using data provided by the State Information System on Drug Abuse (SEIT). To assess the association of some factors with use of the intravenous route crude and logistic analysis was performed. RESULTS: The prevalence of intravenous administration in this population was 64.4% with regional differences ranging between 33% and 90%. Crude and logistic analysis demonstrated a strong association with two factors in addition to geography: the year of first use and the age at first use (the earlier the first use, the greater the strength of the association). CONCLUSIONS: These findings are of paramount importance for the control of the HIV epidemic in Spain and further study in this area could help to guide policy development. PMID- 8002197 TI - A prospective study of proneness to acute respiratory illness in the first two years of life. AB - BACKGROUND: This study sought explanations for the proneness to respiratory events in young Australian children. METHODS: Prospective respiratory symptom diaries on 836 children collected data on respiratory symptoms and episodes. Questionnaires to mothers and birth and pregnancy records provided 56 known and possible predictors which were tested against two summary respiratory outcomes in each of the first and second years of life. RESULTS: The two summary respiratory variables recorded for first and second year of life give four outcome variables. In fitting multivariate regression models to predict outcomes, use of child care in early childhood and mothers' experience of respiratory illness in the 12 months before birth were significant predictors for all four outcomes. Number of siblings was a predictor for three of the four outcomes. Sleep difficulty during pregnancy in the mother, and respiratory hospitalization of the infant in the first year, were significant predictors for both first-year outcomes. Unexpected and unexplained findings emerged for alcohol intake during pregnancy, passive smoking and breastfeeding in relation to the second year respiratory outcomes. Less than 9% of variance in outcome scores was explained in any of the four multiple regression models but this rose to between 24% and 31% when a corresponding score from the other year was added to the model. CONCLUSIONS: Proneness to respiratory illness is an important entity; its determinants are largely unknown and events in pregnancy or the perinatal period explain only a small proportion of the between-infant variability. PMID- 8002196 TI - Demographic factors associated with HTLV-1 infection in a Gabonese community. AB - An epidemiological study of human T-lymphotropic virus type 1 (HTLV-1) and syphilis has been carried out in a multiethnic community of seven neighbouring villages located in eastern Gabon on 1240 subjects over 5 years old (82.7% of the population in this age range). Antibodies to HTLV-1 (anti-HTLV-1) were detected by ELISA with confirmation by Western Blot and antibodies to syphilis by Venereal Diseases Research Laboratory assay with confirmation by the Treponema pallidum haemaglutination assay. The prevalence rate of anti-HTLV-1 was 8.5% and increased from 3.7% in the 5-14 years age group to 23.8% in the over 60 years age group. Logistic regression showed that the positivity for anti-HTLV-1 was associated with age, ethnic group and sex (higher prevalence in females). The seroprevalence rate of syphilis was 8.2%. Seropositivity for syphilis and HTLV-1 were related but age was a confounding variable in this relationship. This study showing a highly heterogeneous distribution of HTLV-1 in a geographically limited area suggests the role of environmental and behavioural factors in HTLV-1 transmission. PMID- 8002198 TI - Validity of a respiratory questionnaire to identify pneumonia in children in Lima, Peru. AB - We conducted a nested case-control study utilizing cases of clinical pneumonia identified in a community-based prospective surveillance study of children under 3 years of age in order to test the validity of a survey questionnaire. Three types of sex- and age-matched concurrent controls were selected from the surveillance population: acute respiratory infection (ARI) clinic controls. ARI community controls and healthy community controls. Survey interviews were scheduled at random for any of four consecutive 7-day periods after the diagnosis of the case. The questionnaire covered a 30-day recall period. The combination of cough with fast breathing or shortness of breath, and with fever, provided the highest positive predictive value for pneumonia. The sensitivity of some questions dropped when the interview took place more than 15 days after the diagnosis of the case. However, the utilization of a 15-day recall period did not increase the positive predictive value of the survey. We conclude that in this trained population under surveillance, a survey questionnaire utilizing a 30-day recall period and using the combination of cough, fast breathing or shortness of breath and fever to define episodes with a high likelihood of pneumonia, offers an acceptable tool for the monitoring and evaluation of respiratory control programmes. This questionnaire needs further evaluation in an untrained population and in other regions before it can be adopted for use in ARI control programmes. PMID- 8002199 TI - Multidrug therapy and eye disease in leprosy: a cross-sectional study in the People's Republic of China. AB - BACKGROUND: Factors associated with leprosy-related eye disease in a multidrug therapy (MDT) treated population in China were assessed to determine if status prior to inclusion in the MDT programme (newly diagnosed leprosy patient or leprosy patient on prior dapsone monotherapy) contributed to the prevalence of ocular pathology. METHODS: Trained leprosy paramedical workers in Sichuan Province examined 974 leprosy patients in a standardized fashion. Univariate analyses and multiple logistic regression were used to assess the contribution of demographic and clinical parameters to leprosy-related eye disease. RESULTS: In both groups (prior dapsone and new MDT) leprosy-related eye disease was associated with a longer distance to leprosy health worker or health centre. Among patients with a history of prior dapsone monotherapy, age and duration on dapsone monotherapy were also associated with leprosy-related ocular morbidity. Among newly diagnosed leprosy patients the prevalence of ocular morbidity remained between 8% and 11% regardless of when the patient started MDT. CONCLUSIONS: Our findings suggest that, even when case detection is good, ocular pathology will still occur in MDT treated leprosy patients. There remains an important role for health workers in the prevention of ocular morbidity. Our data also demonstrated that pooling of results from all patients (newly diagnosed and on prior dapsone monotherapy) in a leprosy control programme will likely give rise to inadequate estimates of risk of ocular disease due to variable clinical disease histories in these groups. PMID- 8002200 TI - Measles transmission in health facilities during outbreaks. AB - BACKGROUND: Consultation waiting rooms and similar medical settings, either public or private, are places where children have higher probability of acquiring some infectious diseases, especially during outbreaks. METHODS: During a measles outbreak which occurred in Lisbon in 1989 a case-control study was carried out in a major paediatric hospital to estimate the risk of measles infection associated with the exposure in medical settings. The statistical analysis was performed with data matched on age, using conditional logistic regression, to reach a multivariate model which explains the risk in the presence of the main variables of interest. RESULTS: The crude odds ratio (OR), based upon 72 cases and 216 controls, in children younger than 12 years, was 4.1 (P < 0.001). Hospital emergency settings had an OR of 4.9 (P < 0.001) and private physicians' offices an OR of 1.4 (P = 0.689). Non-whites showed a 2.4-fold increase in the crude probability of getting measles, although this was not statistically significant (P = 0.118). Children who had a recent contact with cases of measles had an OR of 14.7 (P = 0.005). Immunization against measles was an important protective factor (OR = 0.1; P < 0.001), as was attendance at kindergartens or wet nurses, although less significant (OR = 0.4; P = 0.051). CONCLUSIONS: This study supports the need for children to avoid unnecessary exposure in medical settings during measles outbreaks, especially if those settings are crowded and result in long waiting periods before a consultation. PMID- 8002201 TI - Sensitivity, specificity and predictive values of health service based indicators for the surveillance of influenza A epidemics. AB - BACKGROUND: The Regional Influenza Surveillance Group (GROG) is a French surveillance network set up in 1984. It collects virological specimens and health service based indicators on a weekly basis. Our aim was to assess the predictive value of the health service based indicators for the detection of influenza A epidemics. METHODS: Virological data were used as a gold standard for defining the epidemics. For each health service based indicator, a statistical threshold was used as a test for the identification of epidemic weeks. Finally, an epidemiological criterion was defined in order to improve the specificity and the speed of detection of outbreaks. RESULTS: Health service based indicators have a positive predictive value of around 0.80. They also advance the detection of outbreaks by between 1 and 4 weeks. CONCLUSIONS: These indicators are easy to collect and are useful for the surveillance of influenza epidemics. Such a system is the prerequisite for the rational use of preventive tools. PMID- 8002202 TI - Family latrines and paediatric shigellosis in rural Bangladesh: benefit or risk? AB - BACKGROUND: The potential benefits of installing excreta disposal facilities on the burden of paediatric diarrhoea in less-developed settings remain controversial. We conducted a longitudinal study to evaluate whether family latrines are associated with interruption of the transmission of shigellosis to younger children in rural Bangladesh. METHODS: We prospectively studied 1529 children under 5 years of age exposed to index cases of Shigella dysentery. In all 219 children with culture-proven shigellosis detected during 1 month of follow-up were compared with 1310 control children who did not develop shigellosis or Shigella-negative dysentery. RESULTS: Overall, the presence of a family latrine appeared to be associated with a higher, not a lower, risk of paediatric shigellosis (adjusted odds ratio (ORa) = 1.37, 95% confidence interval (CI): 0.99-1.89). While use of a pit or sanitary latrine revealed no evidence of a protective association (ORa = 0.96, 95% CI: 0.43-2.15), use of a hanging latrine in which faeces were discharged directly onto the ground or into a body of water was associated with a notable increase of risk (ORa = 1.42, 95% CI: 1.02 1.98, P < 0.05). CONCLUSIONS: While cautioning that installation of sanitary latrines may not be sufficient to reduce the burden of paediatric shigellosis in less-developed settings, these data suggest that eliminating unsanitary latrines constitutes a potentially important intervention in its own right in these settings. PMID- 8002203 TI - Optimal batch size for estimation of the prevalence of a disease using combined samples. AB - Great attention has been given to the combined sample test for its high efficiency. Here a model of mathematical expectation for combined samples has been worked out and used for investigating the prevalence of HCV in serum from blood donors. It was shown that this model was valuable if the probability of a positive test, e.g. the prevalence, is less than 0.31. PMID- 8002204 TI - Ascertainment corrected rates: applications of capture-recapture methods. PMID- 8002205 TI - Pesticides and brain tumour. PMID- 8002206 TI - Transfected lymphocyte extracts of patients with urological tumours: complement temperature-sensitive adenovirus mutants in vitro. AB - Patients with renal or bladder cancers exhibit a unique association with adenovirus (Ad) infections. About 60% of them contain antibodies to Ad early antigens. Both in their tumour cells and peripheral blood lymphocytes (PBL) they have detectable early Ad antigens known to be involved in malignant cell transformation. Transfection of tumour cell extracts resulted in complementing temperature-sensitive (ts) Ad mutants at nonpermissive temperatures (39 degrees C) indicating that some cells of the tumour mass possess active functions for Ad. Only 4 to 18% of control subjects were positive in these tests. Here we studied whether lymphocytes might be involved in tumourigenesis by Ad. PBL extracts of patients were transfected into HEp-2 culture cells, which were subsequently superinfected with Ad-5 ts18 and ts19 mutants at 39 degrees C. Titration of virus yields indicated complementation in 76% of patients with renal and bladder cancers in contrast to 20% of control individuals. Complementing ability of lymphocytes which had been prestimulated with phytohaemagglutinin (PHA) approached that of tumour extracts. It means that both specimens contain advanced functions in contrast to resting lymphocytes. Lymphocytes are nonpermissive for latently carried Ad infections. Expression, possible transfer of early Ad gene products via frequent contacts with tissue cells can result in removal of tumour suppressor gene products from complexes regulating cell cycle negatively. Further interaction with hormone-sensitive protooncogenes explains tissue, age and gender specificity of urological malignancies. These phenomena suggest an important cofactorial role for Ad in kidney and bladder tumours. PMID- 8002208 TI - Slightly dilated acute obstructive failure of congenital solitary kidney. AB - We present a case of a 10-year-old boy with slightly dilated obstructive acute failure of congenital solitary kidney. Obstruction of the ureter by stone was suggested as a cause of renal failure. The dilatation of the urinary tract above the obstruction was very small. PMID- 8002207 TI - Changes in urinary kallikrein excretion and plasma natriuretic factor in a patient with primary aldosteronism with special reference to adrenal histology. AB - High level of urinary kallikrein excretion was observed in a 23-year-old man with primary aldosteronism. Unilateral adrenalectomy improved the clinical symptoms and normalized the urinary concentration of this vasoactive substance. Although plasma atrial natriuretic factor was not elevated, adrenal surgery lowered its concentration. Coexistence of an adrenal adenoma and lesions of nodular hyperplasia were detected in the removed adrenal gland. We summarize the clinical data of this patient and review the literature. PMID- 8002209 TI - Recurrent emphysematous pyelonephritis. A case report. AB - Emphysematous pyelonephritis (EPN) is an uncommon but necrotizing renal infection due to gas-forming coliform bacteria that usually occurs in patients with diabetes mellitus and/or obstructive uropathy. Bilateral EPN is rarely seen and recurrent infection in different kidneys has never been reported in the literature. Here we present a female diabetic patient who experienced two episodes of EPN in different kidneys within 2.5 years, resulting in death eventually. We discuss the pathogenesis, incompatibility between clinical features and radiological findings of EPN, and the principle of management for this life-threatening infection. PMID- 8002210 TI - Renal oncocytoma. A rare entity in Poland. AB - Renal oncocytoma represents a special category of renal tumours and accounts for 3-5% of renal neoplasms. Usually they are incidental findings. Most reports have demonstrated their benign nature but a few cases of high-grade oncocytomas were reported to have metastasized. In Poland, between 1971 and 1991, 7 patients (4 women, 3 men) underwent radical nephrectomy for oncocytoma. The author describes here one case of rare oncocytoma malignum. PMID- 8002211 TI - Splenic injury: a rare complication of percutaneous nephrolithotomy. AB - Splenic injury in the course of percutaneous nephrolithotomy is extremely rare. We report on a splenic perforation and subcapsular haematoma of a female patient who was treated for staghorn stone in the left kidney by percutaneous nephrolithotomy. The splenic injury without external bleeding was diagnosed by ultrasonography and computed tomography. The patient was subjected to splenectomy. PMID- 8002212 TI - Urachal calculi: a case report and review of the literature. AB - A 59-year-old man presented with lower abdominal pain. Plain X-ray of the urinary tract revealed radio-opaque shadows in the suprapubic region. Cystogram and intravenous urography showed these shadows in relation to the anterior part of the bladder. On cystoscopy, a small opening leading to a sac was seen. This was excised and stones were retrieved. The histology of the excised mucosa confirmed inflamed urachus. Four years later the patient remains asymptomatic. PMID- 8002213 TI - Xanthogranulomatous cystitis: a case report and review of the literature. AB - Xanthogranulomatous cystitis is a rare benign chronic inflammatory disease of unknown aetiology. We report a case of xanthogranulomatous cystitis. The patient is well more than 15 years after partial cystectomy. The relevant literature is reviewed. PMID- 8002214 TI - Unusual complication of suprapubic cystostomy. A case report. AB - An unusual case of inadvertent ureterostomy following suprapubic cystostomy is described. The case itself was unusual with unexpected obstruction at the bladder outlet. PMID- 8002215 TI - Near-diploid transitional cell carcinoma: a preliminary report. AB - DNA ploidy analysis has been accepted as an important prognostic factor for patients with transitional cell carcinoma (TCC). However, there was few information dealing with the clinical relevance of slightly aberrant DNA content by flow cytometry (FCM). Here we present five cases of near-diploid (ND) tumours, with DNA index (DI) varying from 0.92 to 1.14, obtained from a prospective study of fifty-one cases (9.8%). The frequency of ND tumours showed a tendency to decrease with increasing tumour stage. Higher fraction of tumour proliferation, defined by Ki-67 index, showed a steady increment from 3.4 to 23.5% with occurrence of gross chromosomal changes. In contrast, the expression of epidermal growth factor receptor (EGFR) decreased from 48.3 to 35.3% for diploid (n = 29) through aneuploid (n = 17) tumours. All three ND bladder cancers had recurrence of one to three times with median follow-up of 36 months. The incidences of tumour recurrence (60%) and cancer death (20%) in ND tumours were intermediate between the aneuploid and diploid TCCs. But, flow DNA analysis of paraffin embedded ND tumours revealed wide and symmetrical G0/G1 peak with DI varying from 5.6 to 13.0. Our limited experience suggests the necessity of special treatment for G0/G1 peaks having CV values greater than 5.5% from paraffin-embedded urothelial carcinomas. PMID- 8002216 TI - Routine use of ultrasound and flexible cystoscopy in the control of benign bladder tumours. AB - During the period 1987-1992, 99 patients with benign bladder tumours were followed regularly with transabdominal ultrasound of the bladder and out-patient flexible cystoscopy. Thirty-five patients had recurrent bladder tumours, but in only one case was there progression to invasive tumour. Seventy-six per cent of the recurrences were diagnosed by flexible cystoscopy while 22% were found by ultrasound. Compared to conventional follow-up programs with in-patient rigid cystoscopy the combination of ultrasound and flexible cystoscopy proved to be safe, highly acceptable by the patients and cost-effective. PMID- 8002217 TI - Treatment of bladder carcinoma in situ with mitomycin C: long-term follow-up. AB - Mitomycin C (MMC) was given intravesically to 14 patients with transitional-cell carcinoma in situ of the bladder (CIS) between 1985 and 1989. Of the 10 patients with complete response two presented progression during the follow-up: one of them in T2 at the 32nd month, and one had a relapse of CIS with diffusion to the prostatic urethra at the 34th month: both patients underwent cystectomy. One patient died of an unrelated cause. At the 48th month 5 out of 7 patients were free from neoplasm. Neoplastic recurrence occurred in 3 patients: one responded to a second endoscopic resection and instillation of MMC, two presented further recurrences. Two patients underwent cystectomy: one for neoplastic progression and one for involvement of the prostatic urethra. MMC seems to be effective in the treatment of CIS of the urinary bladder and the unresponsiveness to chemotherapy must be considered as an adverse prognostic factor for the progression of the neoplasm. PMID- 8002218 TI - Chronic ischaemia of the ileal neobladder: clinical manifestations and management. AB - Recently, bladder replacement with intestinal reservoir is becoming more common as urinary diversion in a selected group of patients after radical cystectomy. Complications occurred in two patients, 2 and 7 months, respectively, after successful radical cystoprostatectomy and reconstruction of the ileal neobladder, due to chronic ischaemic changes of the latter. Their clinical manifestations and management are discussed. Some of the possible potential mechanisms responsible for ischaemic changes of the reservoir are reviewed. PMID- 8002219 TI - Advantages of converting incontinent to continent urinary diversion. AB - A modified Mainz pouch with catheterizable stoma was constructed in six patients who had originally undergone incontinent urinary diversion by ureteroileostomy 7 to 22 years previously for bladder exstrophy or neurogenic bladder with total urinary incontinence. The surgical technique differed from the standard as follows: after stomal excision, the preexisting ileal loop was detubularized and combined with additional ileal and colonic segments for pouch construction. In patients in whom the original ureteroileal anastomoses were patent and the contrast medium refluxed freely to the upper urinary tract during loopography, the ureters were not reimplanted but kept intact. In all patients the ileal valve was connected as stroma to the umbilicus. In addition, two patients underwent construction of a standard Mainz pouch. One had had primary ureterosigmoidostomy and the other one ureterostomies, 10 and 3 months previously, respectively. The urodynamic characteristics of the reservoir were normal in all. In six ureteropelvic units dilation improved significantly and in two patients the bilateral loop-ureter reflux diminished. Long-term follow-up (up to 45 months) showed no further impairment of the kidneys. PMID- 8002221 TI - [AIDS]. PMID- 8002220 TI - Testicular seminoma: 20-year experience at the Northern Israel Oncology Center (1968-1988). AB - Eighty-four patients with testicular seminoma were treated at the Northern Israel Oncology Center during the years 1968-1988. Using the staging classification of Hussey, 69 patients (82%) had Stage I, eight (10%) had Stage IIA, four (5%) had Stage IIB, one (1%) had Stage IIIA, and two (2%) had Stage IIIB disease. Sixty nine patients (82%) had classic pure seminoma, nine (11%) had anaplastic seminoma and six (7%) had spermatocytic seminoma. Seventy-four patients (88%) underwent high inguinal orchiectomy and ten (12%) had a scrotal approach. Seventy-five patients (85%) were treated with postoperative irradiation. Stage I patients received 26-30 Gy to the paraaortic and ipsilateral pelvic lymph nodes. Stage IIA patients were treated in the same manner with a boost to the involved lymph nodes. With a mean follow-up of 97 months, 65 patients (77%) are alive and well with no evidence of disease, 7 patients (8%) are dead due to disease progression. The 5-, 10-, 15-, and 20-year actuarial survival for all patients was 90%, and for early stage patients 94%. Eight patients (14%) relapsed; 3 of them were salvaged by chemotherapy. Serious side effects of irradiation included lethal respiratory failure due to bleomycin-induced pulmonary fibrosis in one patient, peptic ulcer in three patients, hydronephrosis due to paraureteral fibrosis in one patient and recurrent paralytic ileus in one patient. Eight patients (10%) developed nine second cancers, three of them within the previous radiation field.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8002222 TI - [The dynamics of HIV variation]. PMID- 8002223 TI - [Antiretroviral therapy. Current status and perspectives]. PMID- 8002224 TI - [Prevention of HIV-associated opportunistic infections]. PMID- 8002226 TI - [Possibilities and limits of HIV treatment in general practice]. PMID- 8002225 TI - [HIV-associated non-Hodgkin lymphomas]. PMID- 8002227 TI - [HIV infection/AIDS. Strategies for prevention]. PMID- 8002228 TI - [The safety of blood and blood products]. PMID- 8002229 TI - [An unusual course of severe osteoporosis]. PMID- 8002230 TI - [60-year-old patient with diarrhea, collapse and increasing abdominal pain]. PMID- 8002231 TI - [Thrombolytic treatment of acute myocardial infarct]. PMID- 8002232 TI - [What are the therapeutic possibilities in autoimmune thrombocytopenia?]. PMID- 8002233 TI - [Comments on the contribution by D. J. Beuckelmann and E. Erdmann. Digitalis therapy 1994]. PMID- 8002234 TI - [Comments on the contribution by H. E. Blum and W. Siegenthaler. Controversies in therapy of portal hypertension and esophageal varices hemorrhage]. PMID- 8002235 TI - [Drug therapy for the elderly]. PMID- 8002236 TI - Introduction of Nigel W. Daw. 1994 Friedenwald award winner. PMID- 8002237 TI - Mechanisms of plasticity in the visual cortex. The Friedenwald Lecture. PMID- 8002238 TI - Introduction of Richard N Lolley. 1994 Proctor award winner. PMID- 8002240 TI - Keratoconus and contact lens-induced corneal warpage analysis using the keratomorphic diagram. AB - PURPOSE: Videokeratography of early keratoconus may be difficult to distinguish from contact lens-induced corneal warpage, even by experienced examiners. Furthermore, topographic irregularity may be judged inconsistently if quantitative standards are not applied. Quantitative measures based on videokeratographic data were developed and evaluated to determine if improved corneal topographic classification can be achieved. METHODS: The Corneal Irregularity Coefficient (CIC) and Corneal Power Coefficient (CPC) were derived from multiple measures of mean corneal power and its variance for 207 videokeratographs of normal, warped, keratoconus, and keratoconus-suspect corneas. CIC was plotted against CPC, creating a distribution of points representing all maps that tended to be grouped according to surface conditions (the Keratomorphic Diagram). Normal, steep, abnormal, and warped zones were defined by CIC and CPC cutoff values chosen to distinguish normal from keratoconus corneas graphically. RESULTS: Seventy of 76 normal corneas were grouped in the normal zone and 6 in the steep zone; 84 of 84 keratoconus corneas were grouped in the abnormal zone; 35 of 35 contact lens-induced warpage cases were grouped in the warped zone; and 10 of 12 keratoconus-suspect corneas were grouped in the warped zone, with 2 in the abnormal zone. Serially plotted data of keratoconus progression and warpage regression demonstrated that the vector displacement of CIC and CPC values may provide a potentially useful means of distinguishing contact lens-induced warpage from keratoconus-suspect corneas. CONCLUSION: The Keratomorphic Diagram aids in classifying and comparing corneal shape by plotting indices along axes with easily recalled scales. The diagram may become a useful tool to assess presurgical corneal surface instability and postoperative progression of corneal shape change due to healing. PMID- 8002239 TI - The rd gene defect triggers programmed rod cell death. The Proctor Lecture. PMID- 8002241 TI - Computational principles in Purkinje I and IV reflection pattern evaluation for the assessment of ocular alignment. AB - PURPOSE: To develop a standardized reasoning for the evaluation of Purkinje I and IV Reflection Pattern data in primary, secondary, and tertiary positions of gaze in the diagnosis of strabismus with a mathematical approach. To demonstrate the applicability of certain mathematical relations and the appropriate graphic representation of computed ocular alignment data. METHODS: Starting from the known Reflection Pattern Evaluation formulae, equations were derived that allowed for the computation of the relative and absolute positions of the optical and visual axes of both eyes from original data in binocular and monocular fixation. These equations were simplified for clinical use. RESULTS: The authors obtained a set of equations that could be applied to the objective, quantitative analysis of eye alignment in screening for microtropia, in concomitant and incomitant diagnoses of strabismus in primary and nonprimary positions. CONCLUSIONS: Purkinje I and IV Reflection Pattern Evaluation can be extended to the diagnosis of strabismus in nonprimary positions with sufficient clinical accuracy. The newly presented principles and equations serve as a basis for a convenient graphic representation of Purkinje I and IV Reflection Pattern data. These principles of evaluation may be applied to any data dealing with ocular alignment, independently of the method. PMID- 8002242 TI - Measurement of ocular alignment with photographic Purkinje I and IV reflection pattern evaluation. AB - PURPOSE: To provide reference data for the measurement of ocular alignment and of angles of strabismus with a new stationary photographic apparatus at near and at distance fixation; to verify quantitative relations between the data by comparing experimental data with theoretical predictions. METHODS: Use of Purkinje I and IV Reflection Pattern Evaluation in conjunction with a new stationary photographic apparatus; application of previously derived equations; simulation of angles of strabismus of 5 degrees and 10 degrees in the primary position. RESULTS: Data from 62 subjects with orthotropia show good linearity of measured angles in different directions of gaze; a 95% confidence interval for errors up to 18.6% in the simulated angles of strabismus; no need for individual calibration of the apparatus; no bias due to wearing of spherical corrections, and a detection threshold for microstrabismus of +/- 0.35 degrees. CONCLUSIONS: Data concerning orthotropic and simulated strabismus prove the accuracy of Reflection Pattern Evaluation to assess ocular alignment, for instance, for the diagnosis of strabismus in primary and secondary positions, at near and distance fixation. The measuring range can easily be extended to larger angles of strabismus. PMID- 8002243 TI - Effect of acute-phase retinopathy of prematurity on grating acuity development in the very low birth weight infant. The Cryotherapy for Retinopathy of Prematurity Cooperative Group. AB - PURPOSE: To examine the development of grating acuity in four groups of eyes in the Multicenter Study of Cryotherapy for Retinopathy of Prematurity (CRYO-ROP): eyes with no ROP; eyes with less-than-prethreshold ROP; eyes with prethreshold ROP; and eyes with threshold ROP that were randomized to serve as controls (not treated with cryotherapy). METHODS: Subjects were 1398 children with birth weights < 1251 g whose acute-phase ROP was documented as part of the CRYO-ROP study. Monocular grating acuity was measured using the Teller acuity card procedure when children reached 1, 2, 3 1/2, and 4 1/2 years of age. RESULTS: Eyes in the no-ROP and less-than-prethreshold groups showed nearly identical acuity development. Eyes with prethreshold ROP showed mean acuity similar to the no-ROP group at 1 and 2 years, but slightly below the no-ROP group at 3 1/2 and 4 1/2 years. Only 50% of eyes in the threshold untreated ROP group had measurable acuity. These eyes showed mean acuity scores that were approximately 1 octave below those of the no-ROP group at all four test ages. When data from eyes with ROP residua or other ocular abnormalities, and data from eyes of children who were unable to pass the study developmental screening items, were excluded, acuity development was similar among groups. CONCLUSIONS: Mild (less-than prethreshold) ROP has no effect on the development of grating acuity in children between 1 and 4 1/2 years of age. Moderate (prethreshold) ROP is associated with reduced acuity at 3 1/2 and 4 1/2 years. In general, severe (threshold untreated) ROP results in moderate to severe reductions in acuity at all ages between 1 and 4 1/2 years. However, a small number of children with severe ROP show normal acuity development. PMID- 8002244 TI - Increased production of transforming growth factor-beta 2 from cultured human retinal pigment epithelial cells by photocoagulation. AB - PURPOSE: To examine whether laser photocoagulation increased production of growth factors and cytokines, especially transforming growth factor-beta 2 (TGF-beta 2), by cultured human retinal pigment epithelial (RPE) cells. METHODS: Dot blot analysis was performed to identify the changes using the conditioned medium of cultured human RPE cells with or without laser photocoagulation. The following growth factors and cytokines were examined: TGF-beta 1, TGF-beta 2, platelet derived growth factor-BB, epidermal growth factor, interleukin-1 beta, tumor necrosis factor-alpha, and basic fibroblast growth factor. Immunostaining of the photocoagulated RPE cells was also performed by using the antibodies. Growth inhibition assay using mink lung epithelial cells (CCL-64) was employed both to quantitate active and latent forms of TGF-beta 2 secreted in the conditioned media and to determine the type of TGF-beta by using a neutralizing antibody. RESULTS: In dot blot analysis, among the growth factors and cytokines examined, production of TGF-beta 2 was changed most markedly by laser photocoagulation. This result agreed with the immunocytochemical staining pattern. Photocoagulated RPE-conditioned medium inhibited [3H]-thymidine incorporation of CCL-64. The inhibitory activity was blocked by a neutralizing antibody to TGF-beta 2. Production of active TGF-beta 2 was increased from 1.0 pg/cm2 +/- 0.6 pg/cm2 per 24 hours to 11.0 pg/cm2 +/- 1.0 pg/cm2 per 24 hours by laser photocoagulation, and that of total TGF-beta 2 was increased from 11 pg/cm2 +/- 1.0 pg/cm2 per 24 hours to 100 pg/cm2 +/- 20.1 pg/cm2 per 24 hours. CONCLUSIONS: Laser photocoagulation of cultured RPE cells increases their production of TGF-beta 2. It thus seems possible that the TGF-beta 2 produced by the RPE cells plays an important role in the processes that occur after laser photocoagulation. PMID- 8002245 TI - Effect of TGF-beta on interferon-gamma-induced HLA-DR expression in human retinal pigment epithelial cells. AB - PURPOSE: Retinal pigment epithelial (RPE) cells express human leukocyte antigen (HLA)-DR (class II) antigens when stimulated with interferon gamma (IFN-gamma) and may be capable of local antigen presentation. The authors examined the effect of transforming growth factor-beta (TGF-beta), a cytokine normally found in the eye, on the expression of these immunoregulatory molecules in vitro and attempted to determine the mechanism by which this cytokine acts. METHODS: Human RPE cells were cultured in the presence of IFN-gamma and then stained immunohistochemically for HLA-DR antigens. TGF-beta 1 or TGF-beta 2 was added simultaneously with IFN gamma or after 3 days of IFN-gamma treatment. In parallel experiments, RPE cells were pretreated with 4-phorbol-12 myristate-13 acetate (PMA), staurosporine, or calphostin C before stimulation with IFN-gamma or TGF-beta. Quantitative analysis was performed by fluorescence-activated cell sorting. RESULTS: IFN-gamma induced HLA-DR expression on RPE cells. Both TGF-beta 1 and TGF-beta 2 were able to inhibit this effect. These inhibitory effects of TGF-beta were augmented by pretreatment with either PMA or calphostin C. Pretreatment of the cells with PMA before stimulation with IFN-gamma downregulated HLA-DR expression. Staurosporine pretreatment suppressed HLA-DR expression by IFN-gamma-stimulated RPE cells, but this was not additive with TGF-beta. CONCLUSIONS: The authors conclude that TGF beta 1 and TGF-beta 2 strongly inhibit the IFN-gamma-induced upregulation of class II antigens on human RPE cells. The modulation of these IFN-gamma and TGF beta effects by calphostin C, staurosporine, and PMA treatment suggests involvement of the protein kinase C pathway. PMID- 8002246 TI - Interleukin-1-beta changes the expression of metalloproteinases in the vitreous humor and induces membrane formation in eyes containing preexisting retinal holes. AB - PURPOSE: Proliferative vitreoretinopathy occurs when cells migrate into the vitreous humor, where they proliferate and produce a membrane composed of extracellular matrix. Interleukin-1-beta (IL-1-beta) may be involved in these processes because it is chemotactic and mitogenic, and it stimulates metalloproteinase production. In the present study, the effects of intravitreally injected IL-1-beta on retinal membrane formation and the associated changes in metalloproteinase content of vitreous humor were examined. METHODS: Rabbit eyes were injected with IL-1-beta in a buffer, with or without the prior creation of retinal holes. Control eyes received the buffer alone or no injection, with or without retinal holes. Animals were examined by slit lamp biomicroscopy and indirect ophthalmoscopy for 1 month. Zymography was performed on a portion of vitreous humor to assess collagenase content, and the remaining tissue was subjected to histologic analysis. RESULTS: Intraocular IL-1-beta induced perilimbal vessel engorgement, keratic precipitates, synechiae, flare, lens deposits, optic disk hyperemia, and granulomatous formations that gradually subsided during the first week. Intravitreal injection of IL-1-beta in eyes with preexisting retinal holes additionally induced membrane formation. Zymographic analysis of vitreous humor from animals sacrificed 24 hours after IL-1-beta injection showed a 100-kd and a 65-kd gelatinase, whereas control vitreous humor contained predominantly a single gelatinase species of approximately 65 kd. Retinal holes did not affect IL-1-beta induction of the 100-kd gelatinase. CONCLUSIONS: IL-1-beta induces a 100-kd gelatinase in the vitreous humor and epiretinal membrane formation in eyes containing preexisting retinal holes. The presence of retinal holes and abnormal production of cytokines may lead to a cascade of events, including aberrant extracellular matrix remodeling, that result in proliferative diseases of the eye. PMID- 8002247 TI - Choroidal blood flow in the foveal region of the human ocular fundus. AB - PURPOSE: To develop a noninvasive method for the investigation of choroidal blood flow (ChBF) and its regulation in the foveal region of the human ocular fundus. METHODS: Measurement of ChBF was based on the technique of laser Doppler flowmetry (LDF). Sixteen normal subjects (age range, 20 to 64 years), with normal eye examination results, were asked to fixate on a diode laser beam (wavelength = 811 nm, 60 microW at the cornea) delivered to the undilated eye through a fundus camera. Light scattered by red blood cells in the tissue volume sampled by the incident laser beam was detected at the fundus image plane of the camera by an optical fiber. The diameter of the beam at the fundus of the emmetropic eye was about 300 microns. Relative ChBF was measured in both eyes by analyzing the Doppler signal with commercial skin blood flowmeters. The average pulsatile component of ChBF, ChBFP, was determined over the cardiac cycle, and its value was compared to the average total ChBF, ChBFAV. Responses of ChBF to various physiological stimuli, such as increased blood O2 and CO2 concentrations, rapid increases in intraocular pressure, and valsalva maneuvers, were documented. RESULTS: Significant correlations were obtained between the ChBFAV values measured with both flowmeters (P < 0.001) and between the ChBFAV values measured in the right and left eye (P < 0.001). ChBFP represented less than 23% of ChBFAV. ChBFAV was not significantly affected by 5 minutes of breathing 100% oxygen. Raising end-tidal CO2 in one subject from 37 to 59 mm Hg increased ChBFAV by approximately 40%. Acute elevation of the intraocular pressure by suction cup or finger pressure on the globe reduced ChBFAV by as much as 90%. Valsalva maneuvers induced reproducible responses that were very different from those recorded from the skin microcirculation. CONCLUSIONS: Although LDF of the choroidal circulation is still at an early stage of development, this noninvasive method appears to provide continuous and sensitive measurements of relative choroidal blood flow in the foveal region of the human fundus. Near-infrared laser diodes enable measurements through undilated pupils. Examples of responses suggest new avenues in the investigation by LDF of the effect of various physiological stimuli, pharmacologic agents, and pathologic processes on the choroidal circulation in man. PMID- 8002248 TI - Postreceptoral contribution to macular dysfunction in retinitis pigmentosa. AB - PURPOSE: To understand the sites of macular dysfunction in retinitis pigmentosa by evaluating focal electroretinogram (FERG) fundamental and second harmonic components, which are dominated by the activity of the outer and inner retina, respectively. METHODS: FERGs were recorded in response to a uniform field (9 degrees x 9 degrees) flickered sinusoidally at either 8 Hz or 32 Hz. The fundamental components of the responses to both the 8-Hz and 32-Hz stimuli and the second harmonic of the response to the 8-Hz stimulus were measured in their amplitudes and phases. Normal subjects (n = 17), as well as patients with typical retinitis pigmentosa (n = 22), cone dystrophy (CD, n = 7) and X-linked congenital retinoschisis (XLR, n = 5) served as subjects. The fundamental (32-Hz)-second harmonic (8 Hz) amplitude ratio was taken as an index of the relative function of outer-inner layers of the macula. RESULTS: Compared to controls, patients with retinitis pigmentosa showed losses of both FERG fundamental and second harmonic and an increase of the fundamental-second harmonic ratio. Patients with CD also showed losses of both fundamental and second harmonic, but the fundamental-second harmonic ratio was normal. Patients with XLR had a selective loss of the second harmonic, resulting in an increased fundamental-second harmonic ratio. On average, the fundamental-second harmonic ratio of patients with retinitis pigmentosa tended to increase with age. CONCLUSIONS: The results suggest that in retinitis pigmentosa, both receptoral and postreceptoral sites contribute to macular dysfunction. This differs from CD and XLR, where losses appear more selective for the outer and the inner retina. Postreceptoral losses in retinitis pigmentosa may become larger with increasing age. PMID- 8002249 TI - Cosegregation of codon 807 mutation of the canine rod cGMP phosphodiesterase beta gene and rcd1. AB - PURPOSE: To determine if a previously reported nonsense mutation (G to A transition at nucleotide position 2420) in the canine rod cyclic GMP (cGMP) phosphodiesterase beta (PDEB) subunit gene cosegregates with the rod-cone dysplasia 1 disease allele (rcd1) in the rcd1-dog reference colony; to establish the prevalence of this mutation among rcd1-affected Irish setters in the United States; and to screen for this mutation in other forms of canine hereditary progressive retinal atrophy (PRA). METHODS: Exon 21 of canine PDEB, previously reported to contain a nonsense mutation in rcd1-affected dogs, was amplified by polymerase chain reaction from genomic DNA isolated from peripheral blood samples. The mutation was detected in amplified DNA by restriction enzyme digestion and double-stranded conformational polymorphism. Linkage between rcd1 and the PDEB mutation was tested using the computer program LIPED: RESULTS: Three different rcd1-informative canine pedigrees were tested for the PDEB nonsense mutation. The first was a multigenerational pedigree representing the rcd1 reference colony. The other two pedigrees represented purebred Irish setter breeding lines in which rcd1 was known to be segregating. In all three pedigrees, the same point mutation was present and segregated with no discordance with the rcd1 allele. Linkage analysis established a maximum logarithm of odds (LOD) score of 12.05 at a linkage distance (theta) of 0.0. In a representative sampling of Irish setters in the United States diagnosed clinically as affected with typical rcd1 phenotype, all dogs were demonstrated to have the same (codon 807) PDEB mutation. Three of four Irish setters affected with atypical, relatively slower disease also had this mutation, but one dog did not. This point mutation in the canine PDEB gene was absent in other forms of canine hereditary retinal degeneration. CONCLUSIONS: In three informative pedigrees, the codon 807 mutation in canine PDEB cosegregates with the rcd1 disease allele with zero discordance. A linkage distance (theta) of zero, with an LOD score of 12.05, indicates identity of this mutation and rcd1. This appears to be the only mutation causing rcd1 in the United States. In all other forms of canine hereditary retinal degeneration tested (cd, erd, prcd, rcd2, X-linked PRA, and in one Iris degeneration tested (cd, erd, prcd, rcd2, X-linked PRA, and in one Irish setter with late onset PRA), this PDEB point mutation was absent. PMID- 8002250 TI - Corneal electroretinographic function rescued by normal retinal pigment epithelial grafts in retinal degenerative Royal College of Surgeons rats. AB - PURPOSE: This study was designed to examine whether retinal function can be rescued by allogeneic normal retinal pigment epithelial (RPE) grafts in Royal College of Surgeons (RCS) with retinal degeneration and, if so, whether this rescued function can be measured and followed by recording the corneal electroretinogram (ERG). METHODS: RPE donors were RCS-Long Evans crossbred F1 rats with phenotypically normal retinas. Half an RPE sheet was implanted in the subretinal space of RCS rats at postnatal day 20. The fundi of the recipients' eyes were examined, and the corneal ERGs were recorded. The eyes were also examined histologically. RESULTS: The RPE grafts were identified by fundus examination in all 21 recipients. No clinical or histologic evidence of inflammation was detected in the media or the retina of the host eye. Eighteen of 21 (86%) recipients showed rescued corneal ERG function. In nine recipients, the PIII response in the grafted eye was significantly greater than in the nongrafted eye. In the other nine recipients, the ERG in the grafted eye showed a b-wave and an a-wave, whereas no b-wave was detected in the nongrafted eye. Recipients of the sham operation (n = 13) revealed no ERG function rescue. To determine long term corneal ERG function in RPE recipients, 8 of 18 animals in which ERG function was rescued were randomly selected for continued observation. These recipients sustained rescued ERG function for 16 to 17 weeks, at which time the experiment ended. CONCLUSION: Results indicate that retinal function of degenerative RCS rats, as measured by corneal ERG, can be rescued by implantation of allogeneic normal RPE into the subretinal space of the eye. Furthermore, this rescued function can be followed up over a relatively long period of time, thus providing a useful model for studying the functional changes of RPE allografts resulting from either immunologic or neurobiologic influences. PMID- 8002251 TI - Distribution of an endogenous 16-kd S-lac lectin in the chicken retina. AB - PURPOSE: To examine by indirect immunofluorescence the distribution of an endogenous 16-kd S-lac lectin (soluble lactose binding lectin) during development of the chicken retina. METHODS: Cryosections of retinal tissue at different developmental stages and cultured retinal cells (either not permeabilized or permeabilized with acetone) were incubated with a rabbit antiserum that specifically reacts with the retinal 16-kd S-lac lectin. After incubation with a fluorescent-labeled secondary antibody, tissue sections and cultured cells were analyzed by fluorescence microscopy. RESULTS: Retina was weakly stained with the antiserum on early embryonic day 7, whereas on embryonic days 13 and 18 it showed a restricted "granular" staining in the outer retina. At embryonic day 18, in addition, there was widespread staining in all retinal layers. This pattern was maintained by postnatal day 5 and in the adult retina, although the intensity of the staining of the outer retina was weaker. In retinal cell cultures, glial-like flat cells and monopolar, bipolar, and multipolar neurons were stained with the antiserum, but only if they had been previously permeabilized with acetone. CONCLUSION: The results suggest that the distribution of a 16-kd S-lac lectin changes during retinal development. Cell culture experiments indicate that most often the lectin is localized intracellularly in the different retinal cell types. PMID- 8002252 TI - Number and distribution of neuromuscular spindles in human extraocular muscles. AB - PURPOSE: To examine the number and distribution of muscle spindles in all extraocular muscles (EOMs) in humans. METHODS: Thirty-six EOMs were obtained after death from three persons 67, 72, and 83 years of age. Serial sections were made throughout the length of these muscles. Consecutive sections were stained with different methods. To discriminate true spindles from false spindles, light microscopic criteria were defined and were subject to ultrastructural investigation. A distal portion of a single EOM was gained from a multiorgan donor 17 years of age, processed for electron microscopy, and analyzed. RESULTS: Spindles were observed in all muscles studied, with the medial rectus exhibiting a mean of 18.8 spindles +/- 3.0 (+/- standard deviation), the lateral rectus 19.3 +/- 1.9, the superior rectus 15.8 +/- 2.5, the inferior rectus 34.0 +/- 4.4, , the superior oblique 27.3 +/- 8.2, and the inferior oblique 4.3 +/- 1.8 per muscle [corrected]. For each different human EOM, a typical distribution of spindles was observed in the persons examined. The ultrastructural investigation revealed sensory endings in structures primarily identified as spindles. CONCLUSIONS: By comparing 1 g of tissue, spindles are found to be at least as frequent in human EOM as in skeletal muscles known to have a high density of spindles. This fact and the peculiar distribution of spindles in human EOMs suggest that spindles are functionally important proprioceptors in EOM. PMID- 8002253 TI - Separation and characterization of the unknown phospholipid in human lens membranes. AB - PURPOSE: The major component of human lens membranes was thought to be sphingomyelin until 1991, when a study by phosphorus-31 (31P) nuclear magnetic resonance (NMR) spectroscopy revealed the presence of an unknown phospholipid that constituted approximately half the human lens phospholipids. The objective of this work was to isolate this phospholipid and to elucidate its identity. METHODS: The separation of sphingomyelin from the unknown was accomplished using high-performance liquid chromatography (HPLC) and an amino-bound column. Sphingomyelin standard and the membranes from human lenses were chromatographed. Chromatographic fractions were collected and spectrally characterized by proton (1H) NMR and 31P NMR spectroscopy. RESULTS: The chromatographic method did not affect the integrity of the sphingomyelin. Besides the bands corresponding to the unknown components, the chromatogram of the human lens membranes showed three large peaks, the central one with a shoulder, with elution times similar to that for sphingomyelin. The 1H NMR spectra for the fractions collected during the elution of these peaks showed differences. The study by 31P NMR indicated that the first peak contained the unknown phospholipid. The subsequent fractions showed the presence, in different relative levels, of both the unknown and sphingomyelin. By comparison and interpretation of the two-dimensional 1H NMR spectra for sphingomyelin and for the fraction containing the unknown, the unknown phospholipid is proposed to be 4,5 dihydrosphingomyelin, in which the site of unsaturation present in the sphingosine moiety is no longer present. CONCLUSIONS: The ability to separate the unknown from sphingomyelin and the power of 1H NMR spectroscopy allowed the proposition of the identity of the major component of human lens membranes as 4,5-dihydrosphingomyelin. Although the synthetic compound is known to be involved in the formation of extended hydrogen bonding networks, its biologic and physicochemical properties need further study. PMID- 8002255 TI - Molecular biology: the forensic applications. PMID- 8002254 TI - Refractive status in the Beaver Dam Eye Study. AB - PURPOSE: To describe the prevalence of refractive errors in a population of adult Americans. METHODS: From 1988 to 1990, 4926 adults who were 43 to 84 years of age and living in Beaver Dam, Wisconsin at the time of the 1987-1988 census were examined. Refractions were performed according to a modification of the Early Treatment Diabetic Retinopathy Study protocol. Included in this study were 4533 people who had not undergone cataract surgery and who had a best corrected visual acuity better than 20/40 in at least one eye. Myopia was defined as a refractive error less than -0.50 diopters; hyperopia was defined as a refractive error greater than +0.50 diopters. RESULTS: Hyperopia was more frequent than myopia in the study group (age-adjusted of 49.0% and 26.2% in right eyes, respectively, P = 0.0001). The prevalence of hyperopia in the right eye increased with increasing age from 22.1% in those 43 to 54 years of age to 68.5% in those 75 years of age or older. The prevalence of myopia in the right eye decreased from 43.0% in those 43 to 54 years of age to 14.4% in those 75 years of age or older. There was significant relationship between education level and refractive error (age adjusted r = -0.32, P = 0.0001). Neither household income nor occupation was associated with refractive error in our data. CONCLUSION: These cross-sectional data indicate age-related differences in refractive status in an adult population and suggest that education is associated with myopia independent of age. PMID- 8002256 TI - Cavernous haemangiomas of the central nervous system--no longer occult lesions. PMID- 8002257 TI - Intrathecal narcotics in cancer pain--a case report. AB - A 61 year old female patient presented with metastatic bone pain three years post mastectomy. Standard oral analgesics and epidural morphine were ineffective in achieving pain control. Her pain was eventually controlled with morphine sulphate 48 mg daily via a self administered intrathecal pump. These devices are being used with increasing frequency and this case report highlights some of the problems encountered in this patient's management. PMID- 8002259 TI - Employer awareness of epilepsy. PMID- 8002261 TI - E. J. Conway, F.R.S., 1894-1965. PMID- 8002260 TI - Alterations in human endothelial cell morphology, proliferation and function by a macrophage-derived factor. AB - Changes in endothelial cell (EC) morphology occur at sites of physiological lymphocyte traffic and in areas of chronic inflammation. Previous studies have shown that EC shape changes also occur in vitro following exposure of EC monolayers to peripheral blood mononuclear cell (PBMC)-derived conditioned media (CM). In the present study, quantitative image analysis is used to define the cell of origin of the elongating factor(s), to examine changes in EC proliferation and function accompanying PBMC-induced human EC elongation and to identify the active PBMC-derived products responsible for this elongation. By separating mononuclear cells into subpopulations (macrophages, B cells and T cells) and adding conditioned media derived from these subpopulations to cultured ECs, the macrophage (M phi) is shown to be the primary cell of origin of the elongating factor(s). Furthermore, EC elongation is accompanied by both a dose dependent decrease in cellular proliferation and an increase in prostacyclin production. These findings suggest that PBMC-induced changes in EC morphology may be associated with a shift from a proliferative state to a more secretory phase of the EC cycle. Finally, using recombinant factors it is shown that TNF alpha acting in combination with IL-1 may be the active PBMC-derived products which contribute to EC elongation. PMID- 8002258 TI - A review of continuous renal replacement therapy. AB - Patients in the Intensive Care Unit commonly develop acute renal failure (ARF). The kidneys are rarely the only organs failing in these patients. Frequently ARF is part of multiple organ dysfunction syndrome. The choice of dialytic therapy should consider, not only the efficacy of the therapy, but also the undesirable effects such therapy may have on the other failing organs. Intermittent Haemodialysis and Peritoneal Dialysis were the conventional forms of dialysis available. Both are associated with complications which may make them unsuitable for use in the haemodynamically unstable, hypercatabolic patients, seen in the Intensive Care setting. Continuous Renal Replacement Therapy (CRRT) has been introduced in many Intensive Care Units to provide a more stable, flexible form of dialysis. The purpose of this article is to give an overview of the various forms of CRRT and to discuss the advantages of this form of therapy. PMID- 8002263 TI - "How safe is splenectomy?". AB - The increased risk of sepsis in patients following splenectomy has been well documented. Fear of overwhelming post-splenectomy sepsis (OPSI) has resulted in a generalized trend towards splenic salvage among surgeons. However, splenorrhaphy and attempts at splenic salvage may of themselves predispose to significant morbidity, sometimes more serious than increased susceptibility to infection associated with splenectomy. This study aims to assess the risk of splenectomy and subsequent asplenia. We reviewed 246 patients who underwent splenectomy over a 16 year period. Indications for splenectomy were considered under the following headings: haematological (N = 116), trauma (N = 69), visceral carcinoma (N = 28), incidental (N = 13) and miscellaneous (N = 20). There were 28 deaths in the series, primarily among those in the intra-abdominal carcinoma (13) and multiple trauma (13) groups. Two deaths were recorded among patients undergoing elective splenectomy for benign disease. Thrombo-embolic complications were recorded in nine patients; respiratory tract infection in 36 patients and intra-abdominal abscess in two patients. Two cases of post-splenectomy pneumococcal septicaemia were documented, neither of which was fatal. While not an entirely benign procedure, splenectomy can be performed relatively safely, especially when performed for benign disease in an adult population. PMID- 8002264 TI - Giant squamous cell carcinoma of the hand: epithelioma cuniculatum--a case report. AB - We report a case of a giant squamous cell carcinoma of the hand. It demonstrates the natural history of a neglected well differentiated squamous cell tumour in this site. It resembles the epithelioma cuniculatum variant of squamous cell carcinoma, previously described as being peculiar to the foot. PMID- 8002262 TI - Helicobacter pylori and gastro-oesophageal reflux disease--a prospective study. AB - In a prospective evaluation of the relationship between Helicobacter pylori infection and gastro-oesophageal reflux disease (GORD), 93 consecutive patients (47 female: 46 male: mean age, 46 years: range 13-93) with symptoms and endoscopic evidence of GORD were studied. A total of 50 patients (54%) were H. pylori-positive on gastric antral biopsies. No significant correlation was detected between H. pylori status and grade of oesophagitis. The prevalence of H. pylori infection showed a gradual increase with age. Of 64 patients with a hiatal hernia, 28 (44%) had histological evidence of H. pylori infection of the hernia mucosa; 27 of these patients (96%) had associated H. pylori in the gastric antrum. Of the 36 patients whose hiatal hernia was H. pylori-negative, only 6 (17%) had antral H. pylori (P < 0.001). Of the 8 patients found to have Barrett's oesophagus, only 1 had H. pylori detected on the Barrett's mucosa. Our results do not support the presence of a significant association between H. pylori infection and GORD. PMID- 8002265 TI - Extensive unstable psoriasis--morbidity and medical management. AB - Over a 5 year period, from January 1988 to January 1993, 23 patients were admitted with extensive unstable psoriasis, 21 of whom had full case notes available. Over the study period these 21 patients required 45 admissions, the mean duration of each admission being 30.54 days. Those patients living more than 30 miles from our unit required almost twice as many admissions as the city group. In 77% of cases, a precipitating factor for the acute flare was identified, and in 53% of these the precipitating factor was iatrogenic related. These patients are prone to develop complications of which infection is the most common. The complexity of medical management was reflected in the number of cross consultations requested. These findings have implications for the optimal delivery of care to this important sub-group of psoriatics. PMID- 8002266 TI - Employing a practice nurse--role and training implications in an Irish context. AB - All 102 nurses known to be practising as practice nurses in the Republic of Ireland were sent a questionnaire for completion anonymously. A response rate of 56% was obtained. Over half the respondents had commenced practice nursing since the new General Medical Services contract in 1989 following a career break, the median duration of which was 5.5 years. Two thirds had completed midwifery training but only one was a qualified Public Health Nurse. An examination of the tasks performed by the respondents suggests that Irish practice nurses are already filling an extended role beyond their treatment room duties with 46% involved in smoking counselling, 74% in counselling on cholesterol and 37% involved in asthma care. Nurses providing antenatal care or taking cervical smears were not, however, more likely to have completed midwifery training. PMID- 8002267 TI - Food allergy in infants and children: clinical evaluation and management. AB - A total of 122 infants and children up to age 17 (69 males and 53 females) who were referred for food allergy to the Pediatric Allergy and Clinical Immunology Unit were evaluated by complete history, emphasizing the implicated foods, clinical presentation and involvement of various organ systems, physical examination, and prick skin tests to food allergens. Fourteen infants with a history of egg white allergy and positive skin tests to egg white also underwent skin tests (prick and intradermal in 1:100 dilution) to measles-mumps-rubella (MMR) vaccine; 35 children under 3 years old had 41 oral challenges with the suspected foods; and 9 children over 3 years old had 12 oral challenges with the suspected foods. We found that cow milk/humanized milk formula, egg white, soybean, and peanut are the main allergenic foods in the pediatric population. Thirteen children had 13 positive oral challenges: 12 to cow milk/humanized milk formula and one to egg white. Symptoms reproduced by oral challenges included urticarial and erythematous rash, conjunctival itching, angioedema, abdominal pain, vomiting, diarrhea, and rhinorrhea. No anaphylactic shock was reported. Negative skin test has an excellent predictive accuracy for negative oral challenge with the suspected food in children > 3 years old. The negative predictive accuracy of cow milk skin test in children < 3 years was 73%. Positive skin test is not a good predictor of a clinical reaction to food. Oral food challenge performed cautiously in a medical setting is the "gold standard" for diagnosis. MMR vaccine can be safely administered to infants with egg white allergy after skin tests with the vaccine are performed. PMID- 8002268 TI - Achalasia in central Israel, 1973-83: clinical aspects. AB - In the framework of an epidemiologic study we collected data on all the 162 patients with achalasia in central Israel. The mean (+/- SD) follow-up was 9.9 +/ 8.7 years (range 1-52). At the last, as compared to the initial examination, the clinical condition of the patients had improved: 38% were without dysphagia as compared to 0% initially, 67% did not vomit and 92% did not complain of aspiration as compared to 17% and 68% initially, and 67% did not complain of chest pain as against 36% initially. In contrast, X-ray examinations, endoscopy as well as manometry did not show major changes. Esophageal retention of a semisolid radiolabeled meal 10 min after ingestion was 46 +/- 25% initially and 34 +/- 26% at last examination (NS). Medical therapy was given to 99 patients and a beneficial response was initially noted in 65% of them. About 88.7% had a beneficial response to surgery and 82.7% to pneumatic dilatations which were associated with a 7.3% perforation rate. Overall the clinical course of this unselected, regional group of patients was better than expected. PMID- 8002269 TI - Coinfection with hepatitis viruses and human immunodeficiency virus in multiply transfused patients. AB - The prevalence, clinical manifestations and serological markers of hepatitis C virus (HCV), hepatitis B virus (HBV) and human immunodeficiency virus (HIV) infections were studied in 112 multiply transfused patients (49 hemophiliacs receiving either nonheat-treated factor concentrates or cryoprecipitate, 33 thalassemic, 20 refractory anemia and 10 leukemia patients). Positive serological markers for HCV, HBV and HIV were found to correlate with number of donors and duration of disease (logistic regression P = 0.0001 and 0.01 respectively). Viral infectivity was significantly correlated with type of blood product. HCV seropositivity was more common in hemophiliacs treated with nonheat-treated factor concentrates (93%) compared to those receiving cryoprecipitate (37%) or nonhemophiliacs receiving red packed cells (20%) (P < 0.001). Likewise, HBV seropositivity in patients receiving the above blood products was 83%, 61% and 26% respectively (P < 0.001), and HIV seropositivity was 35%, 6% and 0% respectively (P < 0.001). Acute or chronic liver disease was documented in 4 of 14 (28%) HCV-positive patients. Increased liver enzymes were recorded in sera of 43% HCV-positive patients and 18% HBV-positive patients compared to 22% of HBV and 20% HCV-seronegative patients (P = 0.076). Of 47 HCV-positive patients 24 were coinfected by HBV and 9 had triple infection (HCV, HBV and HIV). No solitary HIV infection was found. HIV seropositivity was always accompanied by serologic evidence for HBV with or without HCV infection. PMID- 8002270 TI - Sequence analysis of the new human T cell leukemia/lymphoma virus type I isolate (HTLV-I) in Israel. AB - Recent studies have established the presence of human T cell leukemia/lymphoma virus type I (HTLV-I) in Israel. The entire nucleotide sequence of HTLV-I virus from a previously described HE isolate of a Mashadi Jewish Iranian patient was determined. To further characterize the LTR and env genes from the HTLV-I isolate we employed polymerase chain reaction amplification with subsequent cloning and sequencing of the amplified products on both strands. Sequence analyses of amplified LTR regions of this variant showed marked nucleotide homology of 98% compared to Japanese isolates, while African and Indo-Malay (Papua, New Guinea) and Solomon Island isolates showed more divergence with sequence homology of 95% and 91%. Higher homology of 98-99% was conserved in the amplified HTLV-env gene. In this respect the Iranian isolate was most similar to the African and Japanese isolate and divergent from the Melanesian HTLV-I variant, supporting the theory that HTLV-I may have originated in Africa and reached the Far East by overland trade routes. PMID- 8002271 TI - HIV-2 infection in Israel: a new epidemic? AB - AIDS may be caused by two different retroviruses, HIV-1 and HIV-2. Hitherto only HIV-1 has been reported in Israel. We recently discovered HIV-2 as a solitary pathogen in the blood of two foreign workers from West Africa. In view of the relative ease of travel to Israel, it is essential to perform screening for both HIV viruses in all subjects with an enhanced risk, including visitors from countries with a high incidence of HIV-1 or HIV-2 infection and their contacts. PMID- 8002272 TI - Dermatography--a new discipline with a wide range of applications. AB - Dermatography is the application of tattooing techniques in medicine. In the past, several techniques were tried but none led to reproducible results. Dermatography has been developed over the last 10 years into a technique which is both generally applicable and reproducible. It is a suitable treatment modality for disturbing discolorations and scars of the skin which can be permanently camouflaged. PMID- 8002273 TI - Inflammatory myopathy--early diagnosis and management by serum myosin light chains measurements. AB - The use of serum myosin light chain 1 (MLC1) in the diagnosis and treatment response of a patient with biopsy proven inflammatory myopathy is presented. A serum MLC1 level was elevated at presentation despite a normal creatine phosphokinase level. MLC1 levels more closely paralleled the clinical status than the aspartate aminotransferase and lactate dehydrogenase levels. The results suggest that MLC1 levels may facilitate the early diagnosis and management of patients with inflammatory myopathy. Moreover, the excellent response of our patient to low dose prednisone might suggest that the results of treatment could be improved by early detection and institution of therapy. PMID- 8002274 TI - beta-Galactosidase-modified low density lipoprotein demonstrates increased susceptibility to lipid peroxidation and enhanced uptake by macrophages. PMID- 8002275 TI - Plasma fibronectin levels in patients with coronary artery disease. PMID- 8002276 TI - Anaphylactic reaction to oral diclofenac sodium sustained-release tablet. PMID- 8002277 TI - The selective advantage of Gaucher's disease: TB or not TB? PMID- 8002278 TI - Canine Lyme borreliosis in Israel. PMID- 8002279 TI - Testing for food allergy--who, when and how. PMID- 8002280 TI - Myositis diagnosis--the importance of serology. PMID- 8002281 TI - Spa treatment for arthritis at the Dead Sea area. PMID- 8002282 TI - Maternal immune recognition of pregnancy. PMID- 8002283 TI - Osteoarthritis and chondroprotection. PMID- 8002284 TI - Talmudic aphorisms on diet: IV. Eat regularly! PMID- 8002285 TI - Quaternary naltrexone: its immunomodulatory activity and interaction with brain delta and kappa opioid receptors. AB - To investigate the role of brain opioid receptors in immune reactions, quaternary naltrexone (QNtx), a nonselective opioid antagonist which does not cross the brain-blood barrier, was tested for its immunomodulatory activity and ability to antagonize immunological changes produced by centrally applied delta-receptor agonist methionine-enkephalin (Met-Enk) and kappa-opioid receptor agonist MR 2034. Plaque-forming cell (PFC) response served as an immunological model. For this purpose, different groups of Wistar rats were centrally (intracerebroventricularly, i.c.v.) and peripherally (intraperitoneally, i.p., or subcutaneously, s.c.) treated with different doses of Met-Enk. MR 2034 and QNtx. Centrally injected Met-Enk and MR 2034 induced a dose-dependent potentiation and suppression of PFC response, respectively. Small amounts of i.c.v. given QNtx produced a dose-dependent increase in the number of PFC, whereas peripherally administered antagonist potentiated immune response in a dose-independent manner. A dose of 10 micrograms/kg of QNtx given i.c.v. completely abolished the immunopotentiation by Met-Enk. However, a large dose of 5 mg/kg of QNtx given s.c., did not affect the Met-Enk-induced immunoenhancement. Immunosuppression produced by i.c.v. injected MR 2034 was totally abrogated by prior i.c.v. application of QNtx, but partially blocked by s.c. administration of the antagonist.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8002286 TI - Expression of cholinergic muscarinic receptor subtypes mRNA in rat blood mononuclear cells. AB - The cholinergic system plays a role in the neuroimmune network. White blood cells have been found to express muscarinic and nicotinic cholinergic receptors as well as acetylcholinesterase on their surface, and cholinergic agents have been shown to modulate immune functions. Although the presence of muscarinic receptors on white blood cells has been well documented by binding and functional studies, the subtype(s) of muscarinic receptor present on these cells is still unknown. We have previously shown the absence of m2 muscarinic receptor subtype mRNA in rat mononuclear cells (Costa et al., 1994). The expression of m1, m3, m4 and m5 mAChR mRNA was analyzed in this study in rat peripheral blood mononuclear cells by Northern blotting hybridization experiments and reverse transcription-polymerase chain reaction. Only mRNA of the m3 subtype was detected in rat mononuclear cells, at levels about 100 times lower than in brain. Traces of m4 subtype mRNA were found in lymphocytes, at levels about 10,000 times lower than the cerebral cortex, while m5 mRNA was undetectable. PMID- 8002287 TI - Modulatory effects of eicosanoids on mesangial cell growth in response to immune injury. AB - In a rat model of glomerular mesangial cell immune injury induced by a monoclonal antibody (ER4) against the mesangial cell membrane antigen Thy 1.1 and in which mesangial cell proliferation is a prominent feature, we examined the role of arachidonate 5- and 12-lipoxygenation (LO) eicosanoids and of thromboxane (Tx) in modulating the proliferative response. Significant increments in glomerular cell proliferation, assessed by counting glomerular cells positive for the Proliferating Cell Nuclear Antigen (PCNA) and by the incorporation of [3H]thymidine ([3H]TdR) in mesangial cell outgrowths from explanted glomeruli, occurred during the mesangioproliferative phase of injury. This event was abrogated in animals depleted of leukocytes or platelets prior to administration of ER4 and in animals pretreated with the arachidonate 5-LO inhibitor MK886. Pretreatment with the Tx synthase inhibitor, Furegrelate, or the arachidonate 12 LO inhibitor, Baicalein, had no effect, indicating that eicosanoids of arachidonate 5-LO but not those of 12-LO or Tx modulate mesangial cell proliferation following immune injury. We further identified those 5 lipoxygenation eicosanoids with growth modulatory effects on cultured mesangial cells. Leukotriene (LT)C4 and D4 but not LTB4 or 5-hydroxyeicosatetraenoic (HETE) acid enhanced [3H]TdR incorporation in growth-arrested mesangial cells. This effect of LTC4 and LTD4 was abrogated by the specific protein kinase C (PKC) inhibitor calphostin C, indicating a PKC-dependent mechanism. LTC4 and LTD4 but not 5-HETE or LTB4 also increased mesangial cell mass levels of the endogenous PKC activator diacylglycerol. The observations indicate that leukocyte-derived arachidonate 5-LO eicosanoids modulate mesangial cell proliferation following immune injury. Of these LTC4 and LTD4 are the likely candidates as they promote mesangial cell growth via a PKC-dependent mechanisms. PMID- 8002288 TI - Retinoic acid and steroid hormones regulate IgA production by LPS-stimulated murine spleen cells. AB - We examined the regulatory effects of steroid hormones (beta-estradiol and glucocorticoids) on in vitro IgA production. Addition of retinoic acid (RA, 100 500 nM) to the LPS-stimulated spleen cell culture enhanced IgA production (8-22 fold). Simultaneous addition of beta-estradiol, but not testosterone, enhanced the effect of RA synergistically (a further 2-4-fold). In contrast, glucocorticoids inhibited the reaction. The concentration inhibiting IgA production by 50% was 1 nM, 6 nM and 10 nM for dexamethasone, prednisolone and hydrocortisone, respectively. None of the hormones tested alone affected IgA production by LPS-stimulated spleen cells. Hydrocortisone enhanced the IgG1 production by LPS-stimulated spleen cells. This effect was completely abolished by simultaneous addition of RA. These findings indicate that RA can direct the class-switching to IgA in LPS-stimulated spleen cells, and that beta-estradiol and glucocorticoids have positive and negative regulatory effects, respectively, on the IgA production. PMID- 8002290 TI - Administration of the bacterial extract Broncho-Vaxom enhances radiation recovery and myelopoietic regeneration. AB - In the present study, we show that the bacterial extract Broncho-Vaxom (BV, 500 micrograms/mouse; free of endotoxin) has radiation recovery activity when administered i.p. 24 h before sublethal irradiation. In the postirradiation period (5-12 days), pretreatment of mice with BV induced significantly increased bone marrow cellularity and accelerated myelopoietic regeneration (committed progenitor granulocyte-macrophage colony-forming cells; GM-CFC) in the bone marrow compared with saline-treated controls. The earlier hemopoietic recovery in BV-injected mice was not associated with an increase in the number of bone marrow GM-CFC and CFU-S (colony-forming units-spleen) within 24 h after injection. Simultaneously, a significant diminution in bone marrow cellularity occurred. In addition, the percentage of both GM-CFC and CFU-S in the S-phase of the cell cycle was significantly increased 24 h after a single treatment. In our experiments colony stimulating activity (CSA) in the serum of treated mice was not observed within 24 h after injection. Administration of BV 24 h prior to lethal irradiation, resulted in an increase in the number of surviving mice. Combined administration of BV (24 h) and indomethacin (24 h and 3 h) to mice, prior to irradiation, caused an additional radioprotective effect. These results demonstrate that BV stimulates myelopoietic regeneration and suggest a mechanism by which this treatment protects mice from otherwise lethal irradiation. PMID- 8002289 TI - Effect of the synthetic lipid A-related compound, DT-5461, on resistance to Sendai virus infection in mice. AB - DT-5461 enhanced host resistance to Sendai virus infection in mice. Intranasal (i.n.) administration of 200 micrograms of DT-5461 per mouse 3 days before infection was the most effective administration route, dose and timing. DT-5461 enhanced the cytotoxicity of murine natural killer (NK) cells. In addition, DT 5461 activated murine peritoneal macrophages, resulted in augmented of cytotoxicity and the induction of tumor necrosis factor-alpha (TNF-alpha). Therefore, these immunomodulating activities presented by DT-5461 caused protection against Sendai virus infection. PMID- 8002291 TI - Hepatic and renal blood flow responses to a clinical dose of intravenous cyclosporine in the pig. AB - The immunosuppressant Cyclosporine A (CsA) is considered to induce nephrotoxicity in part by causing vasoconstriction of the glomerular afferent arterioles. Although CsA is widely used in hepatic transplantation, little is known concerning its effects on hepatic blood flow. We used ultrasonic flow probes in an anesthetized swine model to measure the effects of a single 60 min infusion of a clinically comparable dose of CsA (5 mg/kg per h) on hepatic, renal, and supraceliac descending aortic blood flows (n = 7 swine). To account for any change in systemic output or systemic vascular resistance during the 60 min CsA infusion that may non-specifically affect hepatic and renal blood flows, the total hepatic (portal vein plus hepatic artery) and renal blood flows were reported relative to the supraceliac descending aortic blood flow (termed 'fractional' total hepatic and renal blood flows). The fractional total hepatic blood flow decreased significantly (p < 0.05) by 40 min of CsA infusion vs baseline, and continued to decrease throughout the infusion (baseline = 0.38 +/- 0.03 units vs 0.28 +2- 0.05 units by 60 min of CsA infusion). During the recovery period, the fractional total hepatic blood flow increased to a value which was not different from baseline (recovery = 0.38 +2- 0.03 units). Fractional right renal artery blood flow did not change significantly from baseline at any time during the CsA infusion or during the recovery period. We conclude that a single, clinically comparable dose of CsA results in a significant decrease in total hepatic blood flow, and that this decrease is greater than that seen in renal blood flow. PMID- 8002292 TI - Anaphylatoxin C3a induces rapid protein phosphorylation in guinea pig platelets. AB - We investigated C3a signal transduction using guinea pig platelets. Anaphylatoxin C3a induced cytosolic calcium influx and turnover of inositol phospholipids and caused protein phosphorylation via specific C3a receptors on guinea pig platelets. Phosphorylation of 40 kDa and 20 kDa proteins was detected within 30 s after C3a stimulation. From phosphoamino acid analysis of both proteins, it was found that about 80% was serine and 20% was threonine. Phosphorylation was decreased by pretreatment of platelets with calcium blockers, diltiazem and TMB 8. A protein kinase C inhibitor, staurosporine, effectively blocked phosphorylation of both proteins, but H-7 did not. The effects of these inhibitors on platelet aggregation were correlated with their effects on protein phosphorylation. These results suggest that protein-serine/threonine phosphorylation is important for C3a signal transduction in guinea pig platelets and that the isoenzyme of protein kinase C or another kinase probably participates in such protein phosphorylation. C3a also caused protein-tyrosine phosphorylation of 56 kDa and 33-36 kDa proteins within 30 s. Staurosporine effectively blocked phosphorylation of these bands. It is suggested that tyrosine kinase also may be involved in C3a signalling in guinea pig platelets. PMID- 8002293 TI - The technological tether. An introduction to ethical and social issues in high tech home care. PMID- 8002294 TI - Transforming homes and hospitals. PMID- 8002295 TI - The economic impact of high-technology home care. PMID- 8002296 TI - Bringing the hospital home. Ethical and social implications of high-tech home care. PMID- 8002297 TI - Chimeras and odysseys. Toward understanding the technology-dependent child. PMID- 8002298 TI - Moral obligation or moral support for high-tech home care? PMID- 8002299 TI - Chronic disease and the meaning of old age. PMID- 8002300 TI - Institutional care of the elderly. PMID- 8002301 TI - Care for elders with chronic disease and disability. PMID- 8002302 TI - New duties for the sentinels. PMID- 8002303 TI - Treatment of critical illness in the elderly. PMID- 8002304 TI - Why U.S. health care reform is so difficult. PMID- 8002305 TI - Adult daughter caregivers. PMID- 8002306 TI - Elder care in the priorities discussion. PMID- 8002307 TI - Caring for an aging world. Allocating scarce resources. PMID- 8002309 TI - Are there limits to solidarity with the elderly? PMID- 8002308 TI - Four scenarios for an aging society. PMID- 8002310 TI - Aging and the goals of medicine. PMID- 8002311 TI - How we treat the elderly. PMID- 8002312 TI - Medical futility: strike two. PMID- 8002313 TI - What price screening? PMID- 8002315 TI - A common sense prescription for health care. PMID- 8002316 TI - On the quest for the humane physician. PMID- 8002314 TI - Will resources for elder care be scarce? PMID- 8002317 TI - Colonic sphincters revisited: simulators of organic disease. AB - Barium enema examinations establish the presence of neoplastic or inflammatory disease in the colon. Areas of narrowing commonly encountered appear to represent organic disease. These areas are in expected locations throughout the colon and have been described. Not much attention had been given to these areas in recent literature, however, which has led to unnecessary colonoscopies and even surgeries. The sphincters of Rossi, Balli, and Payr-Strauss are involved in nerve reflexes; the sphincters of Hirsch, Moultier, and Busi are a thickening of longitudinal and circular muscle fibers. Cannon's sphincter is an overlap of the superior and inferior mesenteric nerve plexuses. When an area of narrowing is encountered where a known sphincter is located, insufflation of more air, changing patient position, administering 2 mg of glucagon intramuscularly or 0.5 mg to 1 mg intravenously will aid in the distinction between a sphincter and organic disease. PMID- 8002318 TI - Low predictive value of an elevated prothrombin time for bleeding on oral anticoagulation. AB - This study is a retrospective analysis of 39 consecutive patients who had a prothrombin time of over 25 seconds with respect to the bleeding complications. This study finds that the overall risk of bleeding is low, 2/39 (5.1%), that there is no statistical difference in the values of the patients who bled when compared to those who did not, and that patients who bled tended to have a clearly identifiable precipitating event. PMID- 8002319 TI - Prolonged static magnetic field exposure and myeloma. AB - Recently, concern about exposure to electromagnetic fields has been expressed. Although a definite cause and effect between these fields and cancer has not been established, we report a case in which the patient, who slept on a magnetic mattress for 5 years, developed myeloma. PMID- 8002321 TI - Postconcussion symptoms and cognitive functioning in posttraumatic headache patients. AB - Forty-two patients with posttraumatic headache of at least three months duration following motor vehicle accident completed the Postconcussion Syndrome Checklist which assessed their experience of 10 commonly reported cognitive, emotional, and physical symptoms. The patients also completed the Beck Depression Inventory and a brief battery of neuropsychological tests. Results indicated that postconcussion symptoms remained quite prevalent among these subjects. More pronounced postconcussion symptomatology was associated with significantly greater impairment on 6 of 13 measures of neuropsychological functioning. Neither severity of subjects' postconcussion symptoms nor neuropsychological test performance were affected by litigation status. However, depressed subjects reported more severe cognitive and emotional symptoms than did nondepressed subjects. Additional information about postconcussion symptom prevalence and a description of the relationship between self-reported symptoms, cognitive functioning on neuropsychological tests, and depression is provided. The implications of these findings are discussed. PMID- 8002320 TI - Double-blind trial of fluoxetine: chronic daily headache and migraine. AB - This study is the first double-blind placebo-controlled trial of fluoxetine for chronic daily headache (CDH) and migraine. After a one month single-blind baseline on placebo, subjects with CDH (n = 64) and migraine (n = 58) were randomly assigned to a three month trial of fluoxetine (20 mg) or an identical placebo. Fluoxetine and placebo were increased to 40 mg in the second month, depending on patient response. Patients kept daily headache records, and completed 100 mm visual analogue scales (VAS) of headache and mood each month. For the group of CDH patients on fluoxetine, overall headache status (VAS) after three months compared to the end of the single-blind placebo baseline improved a mean of 50% vs. 11% for those receiving the double-blind placebo (P = .029), with 47% vs. 23% improving at least 50% (P = .097, n.s.). Fluoxetine patients showed significant improvement in monthly mood ratings compared to placebo (.001 by the end of the study), and modest but significant improvement in daily records of headache frequency (P = .019) but not pain severity. Significant mood improvements preceded improvement in headache, reaching significance by the end of the second month on fluoxetine (P = .013), while headache improvement emerged only during the third month (P = .001). Double-blind investigator judgement identified more headache improvement in fluoxetine than placebo recipients (40% vs. 22%, P = .032).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8002322 TI - Chronic daily headache in children and adolescents. AB - Recurrent headache is a relatively frequent problem in children and adolescents, with the majority of the research attention focused on pediatric migraine. This study assessed differences in consequences to headaches, coping with headaches, and associated disability in children and adolescents attending a headache clinic who were diagnosed with migraine, chronic daily headache, or carried both diagnoses. Results, generally indicated higher levels of impairment for patient's with chronic daily headaches. These patients were also more likely to use blaming others and wishful thinking as coping mechanisms. Gender and racial status interacted with headache diagnosis to predict parent response patterns and disability outcomes. The results provide initial support for the applicability of Martin's functional model of chronic headaches to a pediatric population. PMID- 8002323 TI - Increased 11-dehydrothromboxane B2 in migraine: platelet hyperfunction in patients with migraine during headache-free period. AB - Several disturbances in platelet function have been reported in migraine and tension-type headache (TH). The plasma 11-dehydrothromboxane B2 (11-dTXB2) is free from artifactual increase during blood sampling, and it can be a reliable indicator of thromboxane A2 (TXA2) production in vivo. TXA2 is a very potent proaggregatory and vasoconstrictory metabolite formed in the platelets. We investigated plasma 11-dTXB2 and 5-hydroxytryptamine (5-HT) levels in patients with migraine during headache-free periods and in patients with chronic TH. The mean value of plasma 11-dTXB2 levels in migrainous patients was significantly higher than those in TH patients and healthy controls. The mean value of plasma 5 HT levels in TH patients was significantly lower than those in migrainous patients and healthy controls. There was no correlation between plasma 11-dTXB2 levels and plasma 5-HT levels in any group. The results suggest the existence of continuous platelet activation in migrainous patients. PMID- 8002325 TI - Headache in Sturge-Weber syndrome. AB - Based on reports of headache in arteriovenous malformations and epilepsy, one would predict that the prevalence of migraine headache in the Sturge-Weber syndrome would be higher than in the general population. A questionnaire designed to determine the prevalence and type of headache by IHS criteria was sent to the 500 members of the Sturge-Weber Foundation. The average age of the patients in this sample (71 patients) was 15 years. The sex ratio was approximately one to one. Headache meeting IHS criteria for migraine occurred in 28% (equally among males and females) compared to 17% in females and 5% in males in the general population. Neurologic deficits occurred in 58% during migraine. The prevalence of migraine in children under the age of 10 (31%) was higher than that reported in the general population (5%) and the age of onset was younger. The mechanism of migraine headache in Sturge-Weber syndrome may be similar to that found in epilepsy and vascular malformations. PMID- 8002324 TI - Chronic paroxysmal hemicrania in a child. AB - Chronic paroxysmal hemicrania (CPH) is a relatively new condition first described in 1973. Since its first description, over 80 cases have been reported worldwide. Very few cases have been reported in children. We report the presentation of an 8 year-old boy to illustrate the problems in diagnosis and treatment of this rare disease in childhood. PMID- 8002326 TI - Low flow dural arteriovenous shunt: another cause of "sinister" Tolosa-Hunt syndrome. AB - A 73-year-old man developed acute, painful, ophthalmoplegia. The pain improved with oral steroids and a diagnosis of Tolosa-Hunt syndrome was made. Review of his angiogram revealed a low flow dural arteriovenous shunt that drained posteriorly. Dural arteriovenous shunts may thus be another cause of "sinister" Tolosa-Hunt syndrome. PMID- 8002327 TI - Side-locked unilaterality and pain localization in long-lasting headaches: migraine, tension-type headache, and cervicogenic headache. AB - Side-locked unilaterality and specific localization of pain are not as well defined clinical characteristics in long-lasting headaches (duration more than 4 hours) as they are in short-lasting forms. We examined side-locked unilaterality and pain distribution at onset and at peak headache in 74 patients with different forms of long-lasting headache: migraine and tension-type headache (IHS) and cervicogenic headache (according to Sjaastad et al). Side-locked unilaterality of pain was found in all forms, but to differing extents - 20.8% in migraine, 12.5% in tension-type headache, while it was a mandatory criterion for cervicogenic headache. The pain tended to localize anteriorly, particularly at onset, in migraine; was more diffuse in tension-type headache; and always began in the occipitonuchal region in cervicogenic headache. Our results may contribute to a better clinical definition of long-lasting headaches. PMID- 8002328 TI - Plasma monoamines in tension-type headache. AB - Clinical and pharmacological data suggest a derangement of central monoaminergic systems in tension-type headache. Biochemical evidence has been rarely recognized. These findings may relate with pathophysiological mechanisms of headache or with underlying depression. We measured platelet-rich plasma serotonin and plasma catecholamines (norepinephrine, epinephrine, and dopamine) in 30 patients with tension-type headache and in 20 healthy controls, using High Pressure Liquid Chromatography. We studied differences between groups and the relation between biochemical parameters and clinical indices evaluating duration and severity of headache and depression. Platelet serotonin levels in tension headache patients were higher than in controls (P < 0.001). Plasma catecholamine levels were lower in patients than in controls (P < 0.001 for epinephrine and dopamine, and P < 0.05 for norepinephrine). There was a positive correlation between dopamine levels and duration of history of headache (r = 0.55, P < 0.05). A negative correlation between epinephrine levels and severity of headache was observed (r = 51, P < 0.01). No correlations were found between monoamine levels and severity of depression. Our results add to the evidence of alterations of monoaminergic central systems in tension-type headache patients. These alterations seem to be independent from the underlying depression and related to the pathophysiologic mechanisms of headache. PMID- 8002329 TI - Video assessment of yawning induced by sublingual apomorphine in migraine. AB - A double-blind, placebo-controlled study was carried out in 14 migraineous outpatients and 8 control subjects to assess yawning response to 0.25 mg of sublingual apomorphine, a dopamine receptor agonist, by means of an audiovisual technique. Apomorphine induced a significantly higher number of yawns than placebo in both groups of subjects, but the effect was significantly greater in migraine sufferers than in controls. The result seems to confirm the previous reported hyper-responsiveness to pharmacological dopaminergic stimulation in migraine sufferers. Moreover, the audiovisual technique seems to be an appropriate tool to study yawning response in man. PMID- 8002330 TI - An epidemiological study of headache among the Monks of Athos (Greece). AB - The Monks of Athos in Greece constitute a particular group with unusual sleep schedule and specific diet. In order to study the frequency of headache among them, a special questionnaire was designed. Four hundred forty-nine monks below the age of 50 were approached, 39 of whom suffered from frequent (more than one episode per month, in the last 6 months) headaches (8.68%). The prevalence of migraine was 1.78% (0.66% with aura and 1.11% without) and of tension-type headache 3.34% (1.33% chronic and 2% episodic). Furthermore, 1.87% of monks suffered from mixed headaches (tension-type and migraine attacks as well). Cluster headache was not traced. PMID- 8002331 TI - Pet ownership and prophylaxis of headache and chronic pain. AB - The belief that having household pets promotes good health is ubiquitous among Americans. Recent studies support this belief where certain medical conditions are concerned. To investigate the advantages of pet ownership in the prophylaxis of headache and other chronic pain conditions, we queried 62 patients suffering from such diseases about whether they owned pets and whether children and other adults shared their households. We similarly queried a control group of 38 patients with various conditions not involving headache or chronic pain. We found that statistically, the experimental group and the control group were not significantly different in their household compositions. In fact, those with headaches and chronic pain, on average, owned slightly more pets and had slightly more children and other adults sharing their households than did those without headache or chronic pain conditions. Thus, contrary to our expectations, pet ownership apparently conferred no analgesic benefits, nor did the presence of children or of other adults in the household confer any benefit to headache and other chronic pain sufferers. PMID- 8002332 TI - Vitamin D and calcium in menstrual migraine. AB - Two premenopausal women with a history of menstrually-related migraines and premenstrual syndrome were treated with a combination of vitamin D and elemental calcium for late luteal phase symptoms. Both cited a major reduction in their headache attacks as well as premenstrual symptomatology within 2 months of therapy. These observations suggest that vitamin D and calcium therapy should be considered in the treatment of migraine headaches. PMID- 8002333 TI - Over-the-counter medication and the treatment of migraine. PMID- 8002334 TI - [Retinoids in chemoprevention of tumors of the skin and mucous membranes. Theoretical principles and practical applications]. AB - Chemoprevention, the use of drugs to prevent invasive neoplasia, has gained increasing significance in recent years. Especially for the skin, chemoprevention will become of importance, because large areas of the skin are exposed to environmental carcinogenic factors. Furthermore, many skin diseases predispose to the development of multiple skin tumors. One group of chemopreventive agents are the retinoids, which are effective modulators of cell proliferation and differentiation in normal as well as in transformed tissues. Though the mechanism of action of retinoids is not yet fully understood at the molecular level, chemoprevention studies have demonstrated the ability of retinoids to prevent the development of skin cancer, particularly in patients with xeroderma pigmentosum, multiple basal cell carcinoma and oral leukoplakia. A better understanding of the carcinogenic process should improve our ability to develop effective chemoprevention strategies. PMID- 8002335 TI - [Drug resistance of malignant melanoma. Mechanisms and possible modulation]. AB - Response rates of metastatic malignant melanoma to cytostatic treatment are disappointingly low. Although immunomodulators such as interferons are more commonly being used in combination with cytostatics, no major breakthrough has been achieved. The mechanisms underlying the high chemoresistance of melanoma cells are so far ill-defined, and investigations are only just being initiated. Several mechanisms of chemoresistance have, however, been studied with other tumours and might be relevant for human melanoma: (1) "Classical" multidrug resistance, determined by the expression of the p-glycoprotein which resembles a membrane pump that eliminates natural and synthetic agents from the cell interior. Different drugs, including calcium antagonists, interfere with its function and can thus modulate chemoresistance. Preliminary data from investigations of these mechanisms indicate that p-glycoprotein is not, however, involved in the multidrug resistance of malignant melanoma. (2) Detoxification, involving glutathione-S-transferases (GST). GST are a multigene family of enzymes which inactivate alkylating agents by conjugation to glutathione. Their relevance for chemoresistance in melanoma has not yet been clarified. (3) Topoisomerase II, which is involved in DNA recombination and DNA transcription events and represents the target of several inhibitory cytotoxic agents. Low levels of the enzyme render cells resistant to the action of specific drugs. Again nothing is yet known regarding the relevance of this mechanism in human melanoma. Further studies of these potentially important resistance mechanisms are thus urgently needed in order to develop more effective therapies for advanced malignant melanoma. PMID- 8002336 TI - [Specific IgM tests in syphilis diagnosis]. AB - A total of 359 sera of untreated patients with syphilis were examined by three methods for the detection of Treponema pallidum specific IgM antibodies, the 19S IgM-FTA-ABS test, the IgM solid phase haemadsorption assay (IgM-SPHA), and the IgM Captia assay. The results were compared and evaluated. In primary syphilis, the 19S-IgM-FTA-ABS and IgM-captia yielded reactive results in all patients, whereas only 40% were positive in the IgM-SPHA; the corresponding values for early latent syphilis wee 96.0%, 89.8% and 73.1%, respectively. In secondary syphilis, the reactivity of one serum out of 27 was missed by IgM captia and that of another, by the IgM-SPHA. Mean values (ELISA units = extinction/cut-off) of IgM-captia were higher in primary (2.25) than in secondary syphilis (1.70). In neurosyphilis, only the IgM-SPHA test detected reactivity in all sera, sensitivity for 19S-IgM FTA-ABS and IgM-Captia was 50.0% and 23.1%, respectively. Specificity of the IgM-Captia test results, determined in 386 sera, was 91.2%. The results of specific IgM tests are essential in the diagnosis of congenital syphilis as well as in the recognition of reinfection; they indicate the need for treatment and are useful in the assessment of the effectiveness of therapy. PMID- 8002337 TI - [Course and prognosis of subacute cutaneous lupus erythematosus. A prospective study of 34 patients]. AB - 34 patients with subacute cutaneous lupus erythematosus (SCLE) were prospectively followed up and examined twice in 1986-1989 and 1990-1991, with a minimal interval of 2 years. The findings obtained were documented in a computerized registry and were evaluated by computer-assisted analysis. Thirty-one women and three men aged 23-66 years at the time of the first documentation (FD) were included in the study. The disease had lasted an average 6.5 years (from a few months to 39 years). Prominent cutaneous manifestations of SCLE were shown by 79.4% of the patients at the first visit compared to 58.8% at the second documentation (SD), whereas the incidence of acrolocalized vasculitis increased (FD 20.6%, SD 41.2%), as did that of Raynaud phenomenon (FD 20.6%, SD 26.5%). Mild extracutaneous symptomatology was found in 70.6% (FD) and in 85.3% (SD) of the SCLE patients. Arthralgia (FD 47%, SD 61.8%) and symptoms suggesting some involvement of the peripheral or central nervous system (FD 29.4%, SD 50%) were noted most frequently. Overall, during the follow-up there was a quantitative mild increase of extracutaneous symptomatology; a significant correlation between the presence of acrolocalized vasculitis and arthralgia was found. In conclusion, the prognosis of SCLE appears rather benign; fulminant courses were not observed. However, the risk of mild systemic involvement clearly increases during the prospective course of the disease, whereby acrolocalized vasculitis can be regarded as a cutaneous marker for extracutaneous manifestations. PMID- 8002338 TI - [Behavior of lipids, other serum parameters and cardiovascular functions in ultraviolet therapy]. AB - During a period of 3 years, four controlled clinical studies in 34 patients with hypercholesterolaemia and 40 healthy persons--in some cases with stratification of the basic cholesterol levels and matched pair formation--were performed to find out the effects of serial sun-like UV irradiation on various serum parameters and blood circulation functions. The following significant effects were observed. Patients with hypercholesterolaemia: increase of HDL cholesterol after termination of the serial UV irradiation, increase of serum 25(OH)D3 levels, decrease of serum triiodothyronine, decrease of serum lactate; healthy persons: decrease of resting pulse rate, decrease of recovery pulse rate, decrease of systolic blood pressure. All effects were induced by application of suberythematous UV doses, i.e. amounts of UV with a relatively low risk of side effects. PMID- 8002339 TI - [Exacerbation of pustular psoriasis in mercury poisoning]. AB - A patient suffering from long-standing pustular psoriasis of the palms was treated for 3 weeks with a mercury-containing drug. Exacerbation into generalized pustular psoriasis developed. Mercury levels in blood and urine were increased. After withdrawal of the mercury preparation, therapy with DMPA (2,3-Dimercapto-1 propane-sulfonic acid), a mercury antidote, was initiated, together with short term treatment with aromatic retinoids and PUVA. Within a few days mercury levels decreased significantly and the skin lesions practically disappeared. PMID- 8002340 TI - [Still's syndrome in the adult (adult-onset Still's disease). 2 case reports and review of the literature]. AB - Adult-onset Still's disease (AOSD) is a rare syndrome of unknown origin consisting of recurrent fever, urticarial rash, arthralgias or arthritides, lymphadenopathia, splenomegalia and nonspecific sore throat. It is always linked with leucocytosis and negative blood cultures; rheumatic and antinuclear factors are mostly negative. Very high ferritin levels are frequent and could be a marker of the disease. We report on two cases and give a review of the literature. PMID- 8002341 TI - [Pacemaker erythema with telangiectasis ]. AB - Pacemaker erythema is a rare, irreversible side effect of cardiac pacemakers, clinically characterized by epifocal teleangiectatic erythema. Histology reveals teleangiectatic vessels in the superficial dermis and a slight perivascular infiltrate. We report on three patients presenting with pacemaker erythema following either pacemaker or defibrillator implantation. The pathogenesis of this histopathologically uncharacteristic lesion is unknown. In contrast to peri- or postoperative pacemaker infections, physical irritation can be considered a possible triggering mechanism. Allergic reactions to the implanted material have been ruled out by negative patch test results. PMID- 8002342 TI - [Schimmelpenning-Feuerstein-Mims syndrome (SFM syndrome)]. AB - We report on the case of a 70-year-old caucasian woman with a large linear sebaceous naevus with multifocal intralesional basaliomas and a lipodermoid of the left eye. This rare finding has been preserved because of the special history of the patient. The naevus spread on the left side from parietal to retroauricular, nuchal and sternal. Because of the patient's cardio-pulmonary insufficiency we excised the basaliomas under local anaesthesia. We also made a partial stripped excision of the left-sided parietal parts of the naevus. PMID- 8002343 TI - [Solitary subcutaneous metastasis of a chondrosarcoma]. AB - We report on a rare case of a solitary subcutaneous metastasis from a chondrosarcoma. The metastasis occurred 7 years after excision of the primary neoplasm. Further investigations revealed no evidence of other metastases. Nevertheless, according to data in the literature, the prognosis has to be considered very poor. PMID- 8002344 TI - [The risk of sexual transmission in various forms of hepatitis]. PMID- 8002345 TI - [The antiphospholipid syndrome]. PMID- 8002346 TI - Health services research in a post-reform world: presidential address to the Association for Health Services Research, June 1994. PMID- 8002347 TI - Research on AIDS and health services research. PMID- 8002348 TI - Correlates of medical service utilization among people with HIV infection. AB - OBJECTIVE: To examine factors affecting the use of inpatient, outpatient, and emergency room services by people with HIV infection. DATA SOURCES AND STUDY SETTING: Study participants are adults with HIV infection receiving services at major providers of medical care in ten U.S. cities. Six interviews were conducted over an 18-month period (March 1991 to September 1992). DATA COLLECTION METHODS: Data on service utilization, personal background characteristics, insurance status, and functional status are based on self-report. Disease stage is based on medical record data. STUDY DESIGN: This is an observational study using a panel survey design. Linear and Poisson regression analyses were conducted to determine the effects of need, enabling, and predisposing factors on the dependent variables of ambulatory visits, emergency room visits, inpatient admissions, and average length of inpatient stay. Analyses use 1,449 respondents who completed the second and third interviews. Independent variables were measured as of the second interview, while dependent variables were measured in the third and fourth interview periods. PRINCIPAL FINDINGS: Service utilization was higher among respondents with AIDS than among those at earlier stages of HIV infection. Functional limitations, experienced pain, and negative mood each were associated with increased service use, over and above disease stage. Black respondents reported more hospital admissions and longer lengths of inpatient stays than white respondents. Lack of insurance was related to reduced service use. The effects of disease stage and functional limitations were reduced among people with public, compared to private, insurance. CONCLUSIONS: While disease stage affects use of medical care, the experience of adverse HIV-related conditions, such as pain or functional limitations, has an additional effect on service use. Persistent racial differences in utilization remain to be explained. Lack of insurance impedes use directly and also modifies the effects of disease stage and functioning. PMID- 8002349 TI - Results of the ACSUS for pediatric AIDS patients: utilization of services, functional status, and social severity. AB - OBJECTIVE: This study describes demographic characteristics of pediatric AIDS patients, describes hospital and community-based service utilization patterns, and analyzes medical and social support service usage patterns with respect to patient demographic characteristics, clinical trial participation, functional/developmental status, and social environment. DATA SOURCES AND STUDY SETTING: Data reported in this study are from the AIDS Costs and Service Utilization Survey (ACSUS) and cover the six-month period beginning March 1991 (N = 135). Pediatric patients who sought care for HIV-related problems were sampled at seven different hospitals in five metropolitan regions of the United States. All of the participating hospitals had clinics specifically serving pediatric patients infected with HIV. The sample consists of HIV-positive patients who had had at least one HIV-related symptom or condition. STUDY DESIGN: A stratified probability sample design guided the sampling strategy, which included oversampling in two large hospitals from two of the five metropolitan areas. Survey data cover an 18-month time period of health care utilization, cost, and financing information from HIV-infected patients and their providers. Utilization measures are standardized to a six-month period. Per capita income, family structure, informal personal network, functional status, and clinical trial participation are tested for associations with patterns of utilization. In addition, a weighted ten-point social severity scale was developed to assess family/household stability. DATA COLLECTION: Data were collected through a screener instrument completed by the person accompanying the child to a hospital clinic visit (usually a a parent), and through two interviews conducted in person with the patients' primary caregivers. Data from the questionnaires were coded and assembled into computerized SAS analysis files by WESTAT: PRINCIPAL FINDINGS: Children in this sample are 62 percent African American, 25 percent Hispanic, and 10 percent White. Medicaid is the primary payer for 92 percent. Mean per capita income is $3,440. Fewer than one-half (41 percent) of the families of the children receive Aid to Families with Dependent Children (AFDC). (AFDC). Within the six-month period, approximately one-third of the sample (29.6 percent) was hospitalized. Mean length of stay was 16.0 days. Clinical trial participation was positively related to mean number of hospital clinic visits and receipt of formal (paid) home care. There were no differences in use of community clinic, mental health, and inpatient facilities by clinical trial status. Participation in clinical trials was positively related to income and negatively related to social severity. In four cities, emergency room use was consistently lower for clinical trial participants than for nonparticipants. CONCLUSIONS: Data from the first six months of the ACSUS pediatric sample suggest that participation in clinical trials may bring about access to social services that appear to reduce emergency room use. However, the findings reported here are descriptive and exploratory. Further multivariate, nonparametric analyses of the full 18-month provider patient merged data set are necessary to confirm the simple correlations found in this study. PMID- 8002350 TI - AIDS treatment costs during the last months of life: evidence from the ACSUS. AB - OBJECTIVE: The volume and cost of services consumed by persons with AIDS (PWAs) during their last months of life are examined in this study. DATA SOURCES: This study utilizes data from the AIDS Costs and Service Utilization Survey (ACSUS). The ACSUS is the most comprehensive survey of medical services that are consumed by persons with HIV. STUDY DESIGN: This study is restricted to persons with AIDS who survived the fifth time period (an approximately three-month period in the early spring and summer of 1992). The types and costs of services consumed during the fifth time period by PWAs who did survive (609) and who did not survive (79) the sixth time period are compared. DATA COLLECTION: The ACSUS consists of six interviews over an 18-month period from Spring 1991 to Fall 1992. PRINCIPAL FINDINGS: Decedents were hospitalized more than four times as many days and experienced more than four times the number of home health visits as survivors. Both the average length of stay (19.3 days for decedents and 10.3 for survivors) and the frequency of hospitalization during the fifth time period (.70 for decedents and .28 for survivors) were higher for decedents than survivors. The levels of outpatient care (including emergency room care) and of prescription drug use were similar for decedents and survivors. CONCLUSIONS: This study shows that the cost of treating decedents is more than three times the cost of treating survivors. PMID- 8002351 TI - The effect of physician practice organization on efficient utilization of hospital resources. AB - OBJECTIVE: This study examines variations in the efficient use of hospital resources across individual physicians. DATA SOURCES AND SETTING: The study is conducted over a two-year period (1989-1990) in all short-term general hospitals with 50 or more beds in Arizona. We examine hospital discharge data for 43,625 women undergoing cesarean sections and vaginal deliveries without complications. These data include physician identifiers that permit us to link patient information with information on physicians provided by the state medical association. STUDY DESIGN: The study first measures the contribution of physician characteristics to the explanatory power of regression models that predict resource use. It then tests hypothesized effects on resource utilization exerted by two sets of physician level factors: physician background and physician practice organization. The latter includes effects of hospital practice volume, concentration of hospital practice, percent managed care patients in one's hospital practice, and diversity of patients treated. Efficiency (inefficiency) is measured as the degree of variation in patient charges and length of stay below (above) the average of treating all patients with the same condition in the same hospital in the same year with the same severity of illness, controlling for discharge status and the presence of complications. PRINCIPAL FINDINGS: After controlling for patient factors, physician characteristics explain a significant amount of the variability in hospital charges and length of stay in the two maternity conditions. Results also support hypotheses that efficiency is influenced by practice organization factors such as patient volume and managed care load. Physicians with larger practices and a higher share of managed care patients appear to be more efficient. CONCLUSIONS: The results suggest that health care reform efforts to develop physician-hospital networks and managed competition may promote greater parsimony in physicians' practice behavior. PMID- 8002352 TI - The effect of Channeling on in-home utilization and subsequent nursing home care: a simultaneous equation perspective. AB - OBJECTIVE: This study explored the relationship between participation in a home/community-based long-term care case management intervention (known as the Channeling demonstration), use of formal in-home care, and subsequent nursing home utilization. STUDY DESIGN: Structural analysis of the randomized Channeling intervention was conducted to decompose the total effects of Channeling on nursing home use into direct and indirect effects. DATA COLLECTION METHOD: Secondary data analysis of the National Long-Term Care Data Set. PRINCIPAL FINDINGS: The use of formal in-home care, which was increased by the Channeling intervention, was positively associated with nursing home utilization at 12 months. However, the negative direct effect of Channeling on nursing home use was of sufficient magnitude to offset this positive indirect effect, so that a small but significant negative total effect of Channeling on subsequent nursing home utilization was found. CONCLUSIONS: This study shows why Channeling did not have a large total impact on nursing home utilization. The analysis did not provide evidence of direct substitution of in-home care for nursing home care because the direct reductions in nursing home utilization due to other aspects of Channeling (including, but not limited to case management) were substantially offset by the indirect increases in nursing home utilization associated with additional home care use. PMID- 8002353 TI - A comparison of work-sampling and time-and-motion techniques for studies in health services research. PMID- 8002354 TI - Empowerment forum: a dialogue between guest editorial board members. PMID- 8002355 TI - New health promotion movement: a critical examination. AB - In the last decade, a revolution has been occurring in the field of health promotion. Guided to a large extent by position papers disseminated by the World Health Organization (WHO) Europe Health Promotion Office, and furthered by the Ottawa Charter, the Epp Report in Canada, the Healthy Cities project, as well as by other efforts, this new health promotion movement has introduced new ideas, new language, and new concepts about what constitutes health and how health promotion efforts should be configured to achieve health. Punctuated by the terms like empowerment and community participation, this movement has generated a whole new discourse about the theory and practice of health promotion. This paper explores the multiple meanings that surround these terms, and the implications for practice, by addressing questions like: What does health mean in this new context? What is empowerment? What does participation look like? Has the tyranny of the professional been replaced by the tyranny of the community? Has anything changed about the practice of health promotion other than the language? Finally, it is argued that an acknowledgment of the multidimensionality of these concepts may facilitate their translation from rhetoric into health promotion practice. PMID- 8002356 TI - Learner developed materials: an empowering product. AB - Freire used very specific materials in culture circles to support an empowering process that allowed learners to define the content and outcome of their own learning. However, the materials themselves were carefully crafted and developed by Freire and his co-workers. This article focuses on an extension of Freire's problem-posing educational methods to include participant involvement in the development and production of their own learning materials. Four linked case examples, one in literacy and three in health education, illustrate the process of participatory materials development and we discuss some issues for facilitators and learners. The production process can be an empowering experience and the product stands as testimony to the participants as self-conscious agents and critical thinkers capable of transforming their world. The resultant materials, geared to a particular locale and reflective of the people and language in the community, can provide a powerful model for those who may not have been involved in the process, but who can identify with the friends and neighbors who developed the materials. Participatory materials development is suggested as a supplement to problem-posing educational experiences and is particularly well suited for community programs. PMID- 8002357 TI - Participatory health development in rural Nepal: clarifying the process of community empowerment. AB - Community-based participatory development empowers villagers to develop community cohesion and confidence, increase their ability to identify, analyze, and priorize their own needs, and organize the resources to meet these needs. An important first step in the process involves establishing a cohesive and functional community group. The authors believe that this is best accomplished through villagers' critical examination of their experiences with development including their understanding of reasons for success or failure, and the gradual emergence of a model of working together that acknowledges and builds on participation and collective expertise. This approach to development is demonstrating encouraging results in a rural area of western Nepal in a university affiliated Canadian/Nepali Health Development Project. This paper describes two mini-projects to illustrate the evolution of group formation through reflection, analysis, and action, and identifies outcomes that could serve as indicators of community empowerment. The paper also presents a generic model of empowerment, and offers lessons learned by the project through the application of the empowerment process to sustainable health development. PMID- 8002358 TI - Health promotion and the discourse on culture: implications for empowerment. AB - To invoke the primacy of culture in health education activities is not only to challenge approaches to health education that overlook or downplay this domain, but to also deepen and extend the possibilities of progressive approaches that focus on culture. Border pedagogy, which seeks to establish a countervoice to Eurocentrism and patriarchy, enhances and magnifies the possibilities that were opened up when critical pedagogy invoked the engagement of students in the production of knowledge. This process of engaging the teacher/interventionists and the students/audiences in the production of meaning, value, pleasure, and knowledge should be central to the mission of health education. It is only through such dialogue where varied cultural expressions are affirmed and centralized that the production of cultural identity can be legitimating and empowering relative to health promotion. PMID- 8002359 TI - Critical pedagogy and its application to health education: a critical appraisal of the Casa en Casa model. AB - Casa en Casa is a popular education project of the community health education section of La Clinica de la Raza, a community-based health clinic in Oakland, California. The author examines the Casa en Casa model for its contributions to furthering health education practitioners' understanding of critical pedagogy and community organizing and their relationship to health education. A description of the project's achievements and the obstacles faced in reaching its goals of community empowerment is followed by an analysis of the weaknesses in the project that may undermine its effectiveness. Recommendations are made as to the importance of linking theory to practice and practice to a long-term vision of social change. PMID- 8002360 TI - Building community for health: lessons from a seven-year-old neighborhood/university partnership. AB - This article presents two case studies highlighting the role of community conflict in the process of community empowerment. A graduate program for community health nurses (CHNs) in a large Midwestern city formed a partnership with a diverse, integrated neighborhood for the dual purposes of enhancing the community's capacity to improve its own health and teaching CHNs community organizing as a means to improve health. Central to the partnership are a broad definition of health, trust developed through long-term involvement, a commitment to reciprocity, social justice, and Freire's model of adult learning. Two initiatives that gave rise to major conflicts between community groups are analyzed. Conflicts, external and internal to the community, proved to be both powerful catalysts and potential barriers to the use of Freirian themes in community organization. Both university and community participants report needing better skills in the early recognition and management of conflict. We conclude that conflict management theory must be integrated with empowerment education theory, particularly when empowerment education is applied in a diverse community. PMID- 8002361 TI - De Madres a Madres: a community, primary health care program based on empowerment. AB - Based on the concepts of empowerment of indigenous women through unity, validation of women as key health promoters, and the acceptance of a community's ability to identify and redress its own health needs, the de Madres a Madres Program was started in a Houston inner-city Hispanic community. The program has become a strategy for mobilizing a total community for health. Indigenous volunteer mothers learned how to provide information to increase access to health care. Information was provided through community coalitions the mothers formed with health clinics, social service agencies, local businesses, schools, churches, elected officials, and the media. Outcome data identified the covert functions of the program to be the enhancement of individual women's self-esteem and power, and the collective enhancement of community self-esteem, power, and economy. The concept of a community economy and a theoretical basis of empowerment of women are discussed in terms of community empowerment for community health. PMID- 8002362 TI - Empowering communities: action research through healthy cities. AB - The Healthy Cities process uses action research to empower communities to take action for health. Five concepts that link community empowerment and action research are: focus on community, citizen participation, information and problem solving, sharing of power, and quality of life. Two city examples from Healthy Cities Indiana, a pilot program of CITYNET Healthy Cities, provide illustrations of these concepts. The dynamics of community participation in action research and the successes and barriers to community participation are presented. Outcomes that empowered the community are suggested: the extent to which Healthy City projects are initiated, their progress monitored, continued action in health supported, resources obtained, and policies promoted that contribute equity in health. PMID- 8002364 TI - Empowerment in Spanish: words can get in the way. PMID- 8002363 TI - Ethnographic approach to community organization and health empowerment. AB - The purpose of this article is to address pertinent issues relative to the association between community organization and health empowerment methods in ethnic communities of colour. It seeks to address these issues by utilizing ethnographic procedures for documenting community health concerns and by advocating for empowerment for people of colour and their participation in coalition partnerships. Increasingly the importance of citizen participation in the planning, assessment, and implementation of community-based health initiatives has been identified as essential for effective health promotion and disease prevention programs. This article argues for the utility of a community organization approach for achieving health empowerment, and subsequently decreasing the excess deaths in communities of colour. The interface of ethnographic procedures, community organization, and development of community owned action plans for programming health interventions is discussed. PMID- 8002365 TI - [Central hearing and perceptual disorders]. PMID- 8002366 TI - [Measuring otoacoustic emissions and middle ear diseases]. PMID- 8002367 TI - [Cervicogenic hearing loss]. AB - Existing investigations of cervical hearing disorders have been carried out predominantly in patients in whom those with vertebrobasilar insufficiencies (VBI) could not be distinguished from patients suffering from functional deficit of the upper cervical spine. Since two different syndromes exist, no statement can be made about cervical hearing disorders. That deafness can occur in VBI is uncontested. In contrast, there remains a dispute whether a "vertebragenic hearing disorder" exists. This latter disorder is believed accompanied by tinnitus, a feeling of ear pressure, otalgia and deafness as symptoms of a functional deficit of the upper cervical spine. In reviewing the medical findings of 259 patients with well-defined functional deficits of the upper cervical spine and symptoms of cervical vertigo, subjective hearing disorders occurred in 15%. Audiometric threshold shifts of 5-25 dB, most often in lower frequencies, were observed in 40%. Additionally, results of click-evoked otoacoustic emissions (OAE) were negative in spite of approximately normal hearing. Findings in 62 patients suffering from vertebragenic hearing disorders are reported before and after chiropractic management. Results indicate that these hearing disorders are reversible, as demonstrated by audiometry and OAE. The therapy of choice is chiropractic manipulation of the upper cervical spine. The commoness of vertebragenic hearing disorders emphasizes their clinical and forensic importance. PMID- 8002368 TI - [Effect of head rotation on the vertebrobasilar system. A transcranial Doppler ultrasound contribution to the physiology]. AB - Examination of the vertebrobasilar system until a short time ago was possible only by invasive and therefore potentially harmful techniques. The results of these studies were also contradictory. The objective of the present study was to determine how blood flow velocity differed in the vertebral arteries during head rotation in normal subjects. The origin of cervical vertigo essentially involves three components that are difficult to distinguish. There are the sensory proprioceptive, vascular and sympathicotonic components. Use of transcranial Doppler sonography (TCD) has now made it possible to measure the flow velocity of the vertebral arteries. In 17 normal probands without vertigo or cervical nystagmus, the mean diameters of the vertebral arteries were measured by means of duplex scanning. TCD was used to determine the mean flow velocities of the vertebral arteries in a median position and after head rotations of 30 degrees and 60 degrees to the left and right. Blood flow velocities in both vertebral arteries were not altered by head rotation. This observation contrasted with that of other publications, which were mainly based on cadaver findings. The results of this study form the basis for further investigations on symptomatic patients with recurring cervical nystagmus and cervical vertigo. PMID- 8002369 TI - [Sense of smell before and after endonasal surgery in chronic sinusitis with polyps]. AB - Although olfactory dysfunction is a common clinical symptom in patients with chronic sinusitis, there are few written reports about the nature, frequency and therapeutic accessibility of the various dysosmias. We analysed pre- and postoperative olfactory function in 78 patients suffering from chronic sinusitis with nasal polyposis. Using a squeeze bottle technique we were able to detect preoperative hyposmia and/or dysfunction of olfactory discrimination in 40% and anosmia in 36%. Only 22% of these patients complained spontaneously of disabilities in smell. Endoscopic surgery improved hyposmias and anosmias in 71% and preoperative dysfunctions of olfactory discrimination in 61%. Postoperative thresholds for 2-phenylethanol and dimethyldisulfide worsened in 9% of all patients. Postoperative olfactory discrimination deteriorated in 11%. Preoperative and postoperative olfactory functions were not predictable in individual cases when nasal polyposis was limited. However, mechanical blockage of the nasal airway was just one of many other pathophysiological factors causing olfactory loss in patients with chronic sinusitis. PMID- 8002370 TI - [Current aspects in diagnosis and therapy of pediatric facial paralysis]. AB - Between 1986 and 1992, 60 children with facial nerve palsy (FNP) were examined at the ORL hospital at Erlangen-Nuremberg University. By using blood and cerebrospinal fluid (CSF)-serological tests acute infection with Borrelia burgdorferi (B.b.) could be proved in 16 of 40 children (40%) whose pareses could not be clarified etiologically at first examination. Whereas all idiopathic FNP patients (22) had normal CSF-results, more than half of the B.b.-infected children showed pathological findings, with pleocytosis indicating meningitis. These findings demonstrated that lumbar puncture should be performed in children with FNP of unclear etiology, particularly in cases with positive borreliosis blood serology. The children with borreliosis received penicillin G or ceftriaxone intravenously for at least 14 days and patients with idiopathic FNP were treated with cortisone either orally alone or intravenously in combination with pentoxifylline and hydroxyethylstarch. The outcome in 95% of the patients showed that complete recovery was similar in borreliosis and idiopathic FNP irrespective of treatment with cortisone. Overall, 88% of the FNP recovered completely, indicating a favorable prognosis of FNP in children. PMID- 8002373 TI - [Surgical treatment of chronic otitis media. II: Cholesteatoma removal, open and closed techniques]. PMID- 8002371 TI - [Cisplatin/5-FU versus carboplatin/5-FU. 5 year follow-up]. AB - Between March 1986 and October 1987, 73 patients with advanced squamous cell carcinomas of the head and neck underwent initial chemotherapy before surgery and/or radiotherapy. Chemotherapy consisted of three courses of carboplatin/5-FU or cisplatin/5-FU. Pretreatment tumor states, remission rates and ages of the patients were comparable. Carboplatin as a modification of cisplatin showed significantly less gastrointestinal nerval and ototoxic side effects. After five years of followup, 30% of the patients treated with carboplatin and 33% of the cisplatinum group were alive and clinically free of disease. In contrast, 97% of all patients treated with sequential chemoradiotherapy have died. The data fails to support a "downstaging" of disease. These results document that the only prognostic factor for long-term survival is histologically complete resection of tumor. Further studies must compare the influence of prior chemotherapy and surgery, both followed by conventional fractionated radiotherapy in resectable tumors. Findings show that induction chemotherapy should not be used for unresectable tumors or for sequential chemo-radiotherapy. The use of carboplatin is preferred since oncological efficiency is comparable while side-effects are significantly less. PMID- 8002372 TI - [Initial clinical experience with taurolidin instillation into the area of the middle area]. AB - In this pilot study 2% taurolidin solution was used for irrigation of infected ears and instillation topically in 10 patients with severe purulent otitis media. The main purpose of the study was to find out whether the application of the taurolidin solution into the middle ear would cause significant pain or not. A slight increase in local pain was found sporadically but was not reason for withdrawing the drug. Twelve of 13 bacterial species isolated prior to treatment were eliminated during the trial, with the otorrhea of most patients stopping after just the first instillation. Audiometric evaluations during and 30 months after therapy did not reveal any ototoxic side effects. Tinnitus was not experienced by any patient during therapy. Overall findings demonstrated that local therapy with taurolidin for patients with severe purulent otitis media was very well tolerated and effective bacteriologically. There were also no therapy related complications or ototoxic side effects. PMID- 8002374 TI - HLA class II antigens in rheumatic fever. Analysis of the DR locus by restriction fragment-length polymorphism and oligotyping. AB - We recently described an association of serologically defined HLA class II antigens DR7 and DR53 with RF. This study aimed at determining more precisely the class II gene associated with the disease. We studied patients and age- and race matched controls. Genomic DNA was digested with four different enzymes and hybridized with HLA cDNA probes for DR beta, DQ beta, DQ alpha, and DP beta genes. RFLP analysis disclosed a fragment of 13,81 kb on Taq I DR beta blots, which correlates with HLA-DR53 and HLA-DR16, according to data from the Tenth International Histocompatibility Workshop. Of 24 patients, 20 (83.3%), were positive for the 13.81-kb/Taq I/DR beta allogenotope, compared with 16 (34%) of 47 healthy individuals (p = 0.000079, Fisher's exact test). Search for specific nucleotide sequences was performed using polymerase chain reaction technique. Oligonucleotides corresponding either to allele-specific DR7 and DR53 sequences, or shared by DRB1 and DRB3, DRB4, or DRB5 sequences were screened. Differences were tested throughout the second exon up to codon 100. Results were as expected by simple comparison with the published sequences of individual alleles. Although a clear association with DRB loci is shown, a susceptibility associated either with an allele or with a unique sequence was not found. A promiscuous presentation of the putative cross-reacting peptide or a heterogeneity of the causative agent might be the origin of these results. Genetic complementarity may be an additional factor defining inherited susceptibility to this disease. PMID- 8002375 TI - Increased level of serum HLA class I antigens in HIV infection. Correlation with disease progression. AB - Analysis of (sHLA-I) antigens in a large number of HIV-positive subjects found a significant increase of their level, but did not detect any change in their molecular profile. Monitoring at yearly intervals for four years of the sHLA-I antigen level in 14 HIV-positive subjects with a normal sHLA-I antigen level at study entry showed a significant correlation between progressive increase of sHLA I antigen level and disease progression. Furthermore, a Kaplan-Meier plot of the frequency of development of AIDS in 34 patients whose cases were followed for 7 years showed that sHLA-I antigen level is a strong predictor of progression to AIDS. Its predictive value is comparable to that of serum beta 2-mu level, greater than that of serum neopterin, and lower than that of CD4+ T-cell percentage. The predictive value of sHLA-I antigen level in combination with serum beta 2-mu level, neopterin level, or CD4+ T-cell percentage is greater than that of each individual variable. These results suggest that measurement of the sHLA-I antigen level may provide useful prognostic information in HIV-positive subjects. PMID- 8002376 TI - An HLA-DRB alpha-helix motif shared by DR11 and DR8 alleles is implicated in the pluriallelic restriction of peptide-specific T-cell lines. AB - The T-cell recognition of HLA-DR-peptide complexes is generally restricted by the polymorphism of the DRB molecules but pluriallelic restriction has been described. The molecular basis of restriction and promiscuity of such peptide specific responses is poorly understood. We isolated a panel of T-cell lines specific for the tetanus toxin peptide p2 (TT830-843) exhibiting pluriallelic restriction by DR11 and DR8 alleles. Fine restriction specificity of the T-cell lines was examined in functional assays against DR oligotyped APCs expressing different variants of DR11 and DR8 alleles. Our results show that (a) polymorphisms between serologically related alleles are relevant in terms of restriction of the peptide-specific T-cell response; in some instances, a single amino acid substitution can determine the restriction of a T-cell line; (b) different patterns of restriction are not the result of specific differences in DR-p2 binding as p2 peptide binds to all DR11 and DR8 alleles tested (DRB1* 1101, -1102, -1103, -1104, 110X, -0801, -0802, -0803, and -0806); and (c) pluriallelic restriction of the peptide-specific T-cell response correlates with the presence of a DRB1 alpha-helix motif (67-71-86) shared by some DR11 and DR8 alleles. Possible implications of pluriallelic restriction of peptide-specific T-cell response in autoimmune disorders associated with DR11 and DR8 are discussed. PMID- 8002377 TI - Analysis of TAP2 and HLA-DP gene polymorphism in psoriasis. AB - TAP2 is a gene, located between HLA-DP and HLA-DQ, whose products form a transporter molecule involved in endogenous antigen processing. Polymorphic residues have been described in this gene. TAP2 is of particular interest because its involvement in antigen presentation makes it a candidate for a disease susceptibility gene. In psoriasis, two clinical subtypes analogous to the situation in diabetes type I with early onset and family history and type II with later onset and without family history have been described. We have previously shown that type I but not type II psoriasis is associated with the HLA DRB1*0701/2, -DQA1*0201, -DQB1*0303 haplotype. To investigate whether this haplotype extends to include particular TAP2 and/or DP alleles, we tested the TAP2 and HLA-DP alleles of a control group (n = 199), patients with psoriasis type I (n = 66), and patients with psoriasis type II (n = 35) by hybridization with SSOs. Our data show that there is no significant correlation between TAP2 and/or HLA-DP gene polymorphism and psoriasis type I and/or type II. We conclude that disease association in type I psoriasis is associated with the extended haplotype HLA-B57, -Cw6, -DRB1*0701/2, -DQA1*0201, -DQB1*0303. PMID- 8002378 TI - An alternative approach to the assessment of gamma delta T-cell clonality in celiac disease intestinal lesions through cDNA heteroduplex analysis of T-cell receptor VJ junctions. AB - We have investigated the clonality of the gamma delta T lymphocytes infiltrating the intestinal mucosa of CD patients and control subjects by means of a simple and powerful method based on the heteroduplex analysis of the TCR VJ junctions. Each V-specific TCR chain, amplified either from fresh biopsy material or intestinal T-cell-line cDNA, is denatured and renatured to allow the random reshuffling of the various strands carrying different junctional sequences, coamplified in the same reaction. The mismatched chains (heteroduplexes) are separated from the matched ones (homoduplexes) through polyacrylamide gel electrophoresis, and whenever one or more T-cell clones are emerging over the polyclonal background, discrete bands are visible by ethidium-bromide staining. Through this method, we have estimated the diversity of the V delta 1-3 chains and a newly described V gene (V delta 8) whose homologue in mice is abundantly expressed in gamma delta iLs. We demonstrate that the well-documented expansion of V gamma 1+ gamma delta lymphocytes in the jejunum of CD patients is polyclonal. Overall, the heteroduplex analysis on fresh intestinal and peripheral blood lymphocytes from both healthy and affected subjects shows a polyclonal pattern of all the V delta+ subsets. In contrast, most intestinal T-cell lines produce oligoclonal patterns, suggesting a dramatic in vitro selection effect. The cell expansion in culture is generally not required for the TCR heteroduplex analysis, which can therefore be applied to rapidly monitor the T-cell response in a variety of physiologic and autoimmune reactions, substituting the standard approach of TCR cloning and multiple VJ sequencing. PMID- 8002379 TI - PS-990, a novel neuritogenic compound from Acremonium sp. AB - A novel compound, PS-990, which induces differentiation of neuroblastoma cells, was isolated from the culture broth of a fungus, Acremonium sp. KY12702. PS-990 inhibited brain calcium calmodulin-dependent cyclic nucleotide phosphodiesterase with an IC50 value of 3 micrograms/ml, and markedly induced neurite extension of mouse neuroblastoma, Neuro2A, at concentrations ranging from 10 to 30 micrograms ml. PMID- 8002380 TI - Caloporoside, a new inhibitor of phospholipases C from Caloporus dichrous (Fr.) Ryv. AB - A new salicylic acid derivative, caloporoside, was isolated from fermentations of Caloporus dichrous. Its structure was elucidated by a combination of chemical and spectroscopic methods. Caloporoside exhibits weak antibacterial and antifungal activities and is a quite selective inhibitor of phospholipase C isolated from pig brain (Ki 12, 3 microM). PMID- 8002381 TI - Isolation and structure elucidation of two new calpain inhibitors from Streptomyces griseus. AB - Two new peptides, a diketopiperazine of N-methyltyrosine (1) and a tetrapeptide containing N-methyltyrosine (2), were isolated from an actinomycete strain Streptomyces griseus. These compounds inhibit the enzyme calpain in the micromolar range and were characterized on the basis of spectroscopic analysis, amino acid analysis and sequencing. The structure of the tetrapeptide N methyltyrosyl-N-methyltyrosyl-leucyl-alanine (2), was also confirmed by total synthesis. PMID- 8002382 TI - TAN-1496 A, C and E, diketopiperazine antibiotics with inhibitory activity against mammalian DNA topoisomerase I. AB - Fungal metabolites with an epi-oligothiadiketopiperazine structure, TAN-1496 A, C and E, were isolated from the culture broth of Microsphaeropsis sp. FL-16144. Their molecular formulas were determined to be C22H28N2O9S2, C22H28N2O9S3 and C22H28N2O9S4, respectively. Structures were determined by comparing the NMR data with those of known diketopiperazine antibiotics, sirodesmins. These metabolites inhibited the relaxation of supercoiled pBR322 DNA by calf thymus topoisomerase I but did not affect the decatenation of kinetoplast DNA by calf thymus topoisomerase II at concentration up to 500 microM. They strongly suppressed the growth of various murine and human tumor cells and induced apoptosis. Moreover, various derivatives were synthesized to investigate the relationship of their functional groups and biological activities. PMID- 8002383 TI - Cororubicin, a new anthracycline antibiotic generating active oxygen in tumor cells. AB - In the course of our screening for antitumor antibiotics which show biological activities by generating active oxygen in tumor cells. Micromonospora sp. JY16 was found to produce a new anthracycline antibiotic designated cororubicin. The structure of cororubicin was elucidated as shown in Fig. 5 on the basis of NMR spectral analysis. Cororubicin generated superoxide radicals in tumor cells and showed cytotoxicity, which was reduced by addition of an antioxidative agent, dithiothreitol (DTT). PMID- 8002384 TI - Isolation and characterization of new 18-membered macrolides FD-891 and FD-892. AB - New 18-membered macrolides FD-891 and FD-892 were discovered from the fermentation broth of Streptomyces graminofaciens A-8890 isolated from a soil sample collected at Yamanashi prefecture Japan. They induce morphological changes of HL-60 cells at low concentration below IC50s and have cytocidal activity against in vitro tumor cell lines. FD-891 showed 2 approximately 7 times stronger activity than doxorubicin whereas FD-892 was 20 approximately 100 fold weaker than FD-891 and doxorubicin. PMID- 8002385 TI - Structures of new 18-membered macrolides FD-891 and FD-892. AB - Structures of FD-891 and FD-892 were determined by extensive NMR spectral analysis as shown in Fig. 1. They belong to such 18-membered macrolides as concanamycins and virustomycin. PMID- 8002386 TI - Leptosins I and J, cytotoxic substances produced by a Leptosphaeria sp. Physico chemical properties and structures. AB - Leptosins I and J, belonging to a series of epipolythiodioxopiperazines, have been isolated from the mycelium of a strain of Leptosphaeria sp. OUPS-4 attached to the marine alga Sargasssum tortile. Their relative stereostructures have been elucidated by chemical and spectral evidence. These compounds exhibited significant cytotoxic activity against cultured P388 cells. PMID- 8002387 TI - Pyrroindomycins, novel antibiotics produced by Streptomyces rugosporus sp. LL 42D005. I. Isolation and structure determination. AB - Pyrroindomycins A and B were isolated from fermentations of culture LL-42D005, a strain of Streptomyces rugosporus. Pyrroindomycins possess potent antimicrobial activities against methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococci. Their structures have been determined by using 1- and 2-D NMR, mass spectroscopy and chemical degradations. Pyrroindomycins are the first natural products that contain the highly unsaturated pyrroloindole moiety. PMID- 8002388 TI - Pyrroindomycins, novel antibiotics produced by Streptomyces rugosporus LL-42D005. II. Biological activities. AB - The pyrroindomycins, a complex of novel antibiotics identified in fermentation broths of "Streptomyces rugosporus" LL-42D005, demonstrated excellent in vitro activity against Gram-positive bacteria. The semisynthetic diacetyl derivative of pyrroindomycin B (pyrroindomycin B-Ac2) was bactericidal for exponential-phase cells, but not for stationary-phase cells. This compound also exhibited marginal protection against a lethal Staphylococcus aureus challenge in mice. The poor in vivo activity of this antibiotic complex may be related to binding to blood components, as suggested by elevated MICs observed in blood-containing media. Incorporation of radiolabeled precursors into DNA, RNA, and protein was inhibited in an exponential-phase culture of Bacillus subtilis within ten minutes of exposure to pyrroindomycin B-Ac2. Microscopic examinations of drug-treated cells revealed lysis within the same ten minute period. These data are consistent with an effect of pyrroindomycin B-Ac2 on the integrity of the bacterial membrane. PMID- 8002389 TI - Aldecalmycin, a new antimicrobial antibiotic from Streptomyces. I. Taxonomy, fermentation, isolation, physico-chemical and biological properties. AB - A new antibiotic, aldecalmycin, has been discovered in the culture broth of Streptomyces sp. MJ147-72F6. Aldecalmycin was purified by solvent extraction, Diaion HP-20 chromatography, silica gel chromatography, Sephadex LH-20 chromatography, HPLC and centrifugal partition chromatography. The 1H and 13C NMR spectra of aldecalmycin showed the presence of keto-enol tautomers. Aldecalmycin is equipotent in inhibiting the growth of sensitive and methicillin-resistant Staphylococcus aureus (MRSA). PMID- 8002390 TI - Aldecalmycin, a new antimicrobial antibiotic from Streptomyces. II. Structure elucidation by NMR studies. AB - A new antibiotic, aldecalmycin (1) was isolated from the culture broth of Streptomyces sp. MJ147-72F6. The 1H and 13C NMR spectra of 1 were complicated due to the presence of a beta-ketoaldehyde moiety. Therefore, 1 was converted into an ethylene ketal derivative (2) and into a dihydroaldecalmycin (3). These derivatives gave assignable NMR spectra. The planar structure was elucidated by using 1H-1H COSY, 2D-HOHAHA, 1H-13C COSY and HMBC spectra of 2. The conformation of the decalin ring was elucidated by using ID-HOHAHA, NOE difference and NOESY spectra of 3. The geometry of double bond in the side chain was determined by NOE difference and NOESY spectra of 3. PMID- 8002391 TI - Aldecalmycin, a new antimicrobial antibiotic from Streptomyces. III. Determination of absolute configuration. AB - The planar structure of aldecalmycin (1) had been determined in the previous paper, together with the conformations of the substituted trans decalin ring having one double bond and the sugar: beta-glucopyranoside type. The absolute configuration of 1 was a following problem to be solved. X-Ray crystallographic analysis of crystalline 4'-6'-O-benzylidenedihydroaldecalmycin (4) revealed the relative configuration. On the other hand, the stereoisomerism of the sugar was determined to be D by the optical rotation value of tetra-O-acetyl-alpha methylglucopyranoside derived from 1. These results established the absolute configuration of 1. PMID- 8002392 TI - New nematicidal and antimicrobial compounds from the basidiomycete Cheimonophyllum candidissimum (Berk & Curt.) sing. I. Producing organism, fermentation, isolation, and biological activities. AB - Six new bisabolane type sesquiterpenoids, cheimonophyllons A (1), B (2), C (3), D (4), E (5), and cheimonophyllal (6) were isolated from the culture fluid of the basidiomycete, Cheimonophyllum candidissimum. The compounds exhibited nematicidal, weak antifungal and antibacterial as well as cytotoxic activities. The main product, cheimonophyllon A (1) (C15H22O4), was also active in the Ames mutagenicity test. PMID- 8002393 TI - The preparation of zaragozic acid A analogues by directed biosynthesis. AB - Zaragozic acid A analogues are produced by an unidentified sterile fungus when it is exogenously supplied with 2-thiophenecarboxylic acid, 3-thiophenecarboxylic acid, 2-furoic acid, 2-fluorobenzoic acid, 3-fluorobenzoic acid, or 4 fluorobenzoic acid. The analogues carry 2-thiophenyl, 3-thiophenyl, 2-furyl, o fluorophenyl, m-fluorophenyl, or p-fluorophenyl group, respectively, at C-6' of the C-1 alkyl side chain replacing the phenyl group of natural zaragozic acid A. All the new analogues of zaragozic acid A possess picomolar inhibitory activity against squalene synthase in vitro. PMID- 8002394 TI - Rapid screening of the antimicrobial activity of extracts and natural products. AB - A spectrophotometric method has been developed for the rapid measurement of the antimicrobial activity of natural products, including crude extracts or pure materials. The assay depends on the measurement of non-specific esterase activity using fluorescein diacetate (FDA) hydrolysis in broth cultures of microbes after they have been treated with test compounds. The assay is accurate, reproducible and economical in both time and materials. The speed and economy of the method make it suitable for the rapid screening of many samples and the bioassay directed purification of antimicrobial substances. The assay can also be used with a wide variety of micro-organisms since most micro-organisms are FDA positive. Applications are described in the fields of marine natural products chemistry and essential oils research. PMID- 8002395 TI - Antitumor activity of SPM VIII, a derivative of the nucleoside antibiotic spicamycin, against human tumor xenografts. AB - The antitumor activity of spicamycin analogue SPM VIII against human stomach, breast, lung, colon and esophageal cancers was compared to that of mitomycin C (MMC) in the human tumor-nude mice xenograft model. Comparative studies of SPM VIII given i.v. at 6 mg/kg/day daily for 5 days and MMC given i.v. at 6.7 mg/kg on day 1 revealed that the antitumor spectrum of SPM VIII showed a different pattern from that of MMC and that SPM VIII caused tumor mass reductions in more tumors than did MMC in colon cancers (4/12 versus 1/11). In addition to this study, a comparative study of SPM VIII given i.v. at 12 mg/kg/day 8 times at 3- or 4-day intervals and 5'-deoxy-5-fluorouridine (5'-DFUR) given po at 185 mg/kg/day 5 days per week for 4 weeks showed that SPM VIII had the highest effect on SC-9 human stomach cancer and COL-1 human colon cancer among the 3 compounds, resulting in a significant reduction of tumor mass. Although other pharmacological studies are in progress, these results suggest that SPM VIII might be a novel antitumor compound effective for human cancers including cancer of the digestive organs. PMID- 8002396 TI - Mitomycin derivatives having unique condensed-ring structures. Their synthesis and antitumor activity. AB - A series of mitomycin derivatives 1-3 having unique condensed-ring structures was synthesized and evaluated for their anticellular and antitumor activity. These compounds were synthesized by the Michael addition of 1.3-dicarbonyl compounds to 6-demethyl-7,7-(ethylenedioxy)-6,7-dihydro-6-methylenemitosanes (4-6, and 14) and the subsequent cyclization. For the preparation of 1. the allyloxycarbonyl (Aloc) group was employable for the protection of the aziridine (1a-N-H), since the deprotection proceeded without decomposition of the substrates under the mild conditions with Pd(0) and HCO2H-NEt3. Among these structurally unique derivatives, compounds 1a, 1b, 1d and 1e were quite potent against HeLa S3 human tumor cells and sarcoma 180 solid tumor in mice. PMID- 8002397 TI - Synthesis of PF1022A, an anthelmintic cyclodepsipeptide. PMID- 8002398 TI - Haloemodins, a new class of endothelin-1 type B (ETB) receptor binding inhibitors. PMID- 8002399 TI - N-methylstreptothricin D--a new streptothricin-group antibiotic from a Streptomyces spp. PMID- 8002400 TI - Novel quaternary ammonium carbapenems: 1 beta-methyl-2-(5'-substituted pyrrolidinylthio) carbapenems. PMID- 8002401 TI - Stevastelins, novel immunosuppressants produced by Penicillium. PMID- 8002403 TI - Antimicrobial metabolites from Lentinus crinitus. PMID- 8002402 TI - Menoxymycins A and B antitumor antibiotics generating active oxygen in tumor cells. PMID- 8002404 TI - Biosynthesis of aldecalmycin. PMID- 8002406 TI - Women of Egypt I. PMID- 8002405 TI - Synthesis and antibacterial activity of novel carbapenems with a catechol or hydroxypyridone moiety. PMID- 8002407 TI - Use of maternity services by pregnant women in a small Nigerian community. AB - Pregnancy is a time when women's health is placed at risk by a host of factors; however, professionals providing antenatal care can reduce that risk by monitoring women's health regularly and offering preventive services. Hygienic delivery services by a qualified attendant also help to reduce risks associated with childbearing. We explored these considerations in a rural Nigerian town by following 60 Yoruba women through pregnancy to childbirth. Although a functioning government maternity center in the community offered a full range of antenatal and delivery services, most of the women did not register for antenatal care until their sixth month of pregnancy or later, and 65% delivered at home. This behavior is explained in terms of (a) fees for delivery services, (b) level of income, (c) cultural beliefs, and (d) education. We conclude that provision of relatively accessible services does not guarantee their use and that other social and cultural considerations must be taken into account. PMID- 8002408 TI - Endemic stress: environmental determinants of women's health in India. AB - The Indian subcontinent stands alone as an area in which women have a lower life expectancy at birth than do men. The differential impact of environmental influences on the health of women in India is examined. The influences can be conceptualized as endemic stress that arises from social and physical environmental determinants of deprivation, inadequate resources, limited role opportunities, and oppressive cultural forces. It is suggested that there is a link between these factors and women's health status. The combined effort of Indian women and international support agencies is suggested as an approach to examining, evaluating, and remediating the problem. PMID- 8002409 TI - Laser endometrial ablation: an alternative to hysterectomy. AB - Laser endometrial ablation has been approved by the U.S. Food and Drug Administration as an alternative to hysterectomy for the treatment of chronic menorrhagia. The purpose of the present study was to document women's feelings and outcomes after having the procedure. In-depth interviews were conducted with 65 women who were among the first to undergo this surgery in the United States. For these women, laser endometrial ablation resulted in the end of enduring unpleasant symptoms without the need for a hysterectomy. Nearly all (91%) of the women considered the ablation a success, and all would recommend ablation to another woman. Access to laser endometrial ablation for all women is one method of decreasing the number of hysterectomies performed. PMID- 8002410 TI - Induction of labor: an integrated review. AB - Women's response to induction and augmentation of labor has received little attention in North America. A review of the literature revealed that these procedures epitomize the use of technology in childbirth. From a psycho-emotional perspective, women respond less positively to induction and augmentation than to spontaneous labor and report less satisfaction with the birth experience. In this review of the research and anecdotal literature, reasons for inattention to induction and augmentation are explored, and the nature of the procedures and women's response to them are examined. PMID- 8002411 TI - Role overload and health: the married mother in the waged labor force. AB - Women are joining the waged labor force in ever increasing numbers, raising the proportion of women who hold multiple roles. Each of these roles frequently place significant time and labor demands on women, causing researchers to speculate on a subsequent negative effect on women's health. Research studies paint colorful images of today's working, married mother but have only begun to identify risks to women's health that might be associated with the increased demands associated with multiple roles. PMID- 8002412 TI - Students' knowledge of the use of herbs and other agents as preparation for sexual intercourse. AB - Interest is growing in the use of herbal and other agents as a preparation for sexual intercourse. Concern has been expressed that such traditional practices, which are widespread in central and southern Africa, may increase women's risks of cervical cancer and infection with the human immunodeficiency virus. We examined the knowledge and beliefs associated with these practices in a sample of educated young men and women in Zimbabwe. We found that there was widespread knowledge of the use of herbs as a preparation for sex and that the purpose of the practice was to enhance men's sexual experience. Both men and women indicated ambivalent attitudes toward the practice; an interesting pattern of actual and perceived expectations was found. The need for preventive health education concerning these practices is discussed. PMID- 8002413 TI - Women of Egypt II. PMID- 8002414 TI - Changing roles of Afghan refugee women in the United States. AB - Refugee women face many challenges, such as traumatic flight, loss of family members and property, and dramatic cultural differences in the country of resettlement. We examined the adjustment issues and role changes of Afghan women refugees in northern California. Afghans comprise the largest refugee population in the world, and continuing political turmoil prevents most Afghans in the United States from returning home. Data are presented from interviews with 32 Afghan women. These interviews were conducted as part of a larger ethnographic study that included participant observation and interviews with 90 Afghans and the American health and social service providers who worked with them. Although similar issues were expressed by most Afghan women, generation influenced the experience of such issues. The elderly suffer from social isolation and lack of respect; the middle generation shoulders the triple burden of housewife, employee, and mediator between children and spouse; and young and single women face culture conflict and the lack of appropriate mates. PMID- 8002415 TI - Mother-daughter identification: Polish and Polish-American mothers and their adult daughters. AB - Toward the goal of furthering our understanding of the mother-daughter relationship, we investigated one aspect of the mother-daughter relationship, the mutual identification that occurs within it. Mutual identification was defined as the process by which a mother and her daughter internalize characteristics of each other. A convenience sample of 81 Polish and 81 Polish-American mother daughter dyads was studied. Mother-daughter identification was measured using a semantic differential (SD) scale that included 12 concepts. Analyses using paired t tests revealed that there was no significant difference between the ratings of the Polish-American mothers and those of their daughters on 7 of the 12 concepts and no significant difference between the ratings of the Polish mothers and those of their daughters on 10 of the 12. There were, however, statistically significant differences between the Polish and Polish-American women's ratings of the concepts. These data are interpreted as support for the theory of mother daughter identification. PMID- 8002416 TI - Predictors of mental health in women of a politically unstable country, the Philippines. AB - In a study conducted in Manila, the Philippines, the relationships among the (a) negative appraisal of and coping with political instability, (b) sociodemographic characteristics, (c) morale, and (d) mood of Filipino women (N = 200) were investigated. Findings were as follows: The political instability in the Philippines had a mild negative impact on the women's lives. The women reported mild depression and moderate morale. Their primary coping style was problem focused coping. A positive relationship was found among annual individual income, educational achievement, and morale. A negative relationship was found among annual individual income, educational achievement, and depression. Negative relationships were also found between negative appraisals of news of brutal murders and morale and between frequent changes in the President's cabinet and morale. A positive relationship was found between affect-focused coping and depression, whereas problem-focused coping and depression were negatively related. No relationship was found between coping style and morale. The findings are discussed from the perspectives of Lazarus and Folkman's (1984) coping theory and Filipino culture. Guidelines for health care delivery are specified. PMID- 8002417 TI - Factors that influence women's nutrition knowledge in Saudi Arabia. AB - We studied knowledge of nutritional needs during pregnancy and lactation in 150 pregnant Saudi women at three primary health care centers in Riyadh, Saudi Arabia. We used an interview schedule to collect data regarding the women's knowledge and to determine the effects of certain independent variables on the knowledge scores. Green et al.'s (1980) PRECEDE model provided the theoretical framework for the study. Descriptive statistics, t test, and chi-square methods were used to analyze the data. The majority of the women had poor nutrition knowledge scores, with no significant differences among the three centers. A positive relationship was found between knowledge score and educational level. Negative relationships were found between knowledge score and number of pregnancies, number of deliveries, and number of living children. The findings have several implications for efforts to improve the health status of women in Saudi Arabia. PMID- 8002418 TI - Postpartum concerns: a study of Tanzanian mothers. AB - Maternal and child health services in Tanzania have succeeded in implementing health care strategies to improve the health of children under 5 years of age. However, health care for childbearing women has not been a focus (Government of the United Republic of Tanzania/UNICEF, 1990). We examined what Tanzanian women perceive as concerns during the early postpartum period. A card sort was used with 50 primiparas and 50 multiparas from the Dar-es-Salaam urban area. Primiparas had significantly more worries and interests than did multiparas. Multiparas had significantly more confidence than primiparas had. Findings correspond to those of studies conducted on North American populations, suggesting that early postpartum concerns may be cross-cultural. PMID- 8002419 TI - Breast cancer and the older woman: information and images. AB - Breast cancer is the most prevalent form of cancer in elderly women. Information on breast cancer explicitly relevant to elderly women was examined in 113 articles in the professional nursing literature and popular magazines. Content analysis on the nature or extent of information about breast cancer indicated that authors in the professional nursing literature and the popular media have inadequately addressed the degree of risk and the special needs of the elderly woman. Few authors in either the lay or professional literature have explicitly discussed the needs of elderly women, nursing research on breast cancer typically did not include elderly women, and popular articles and accompanying photographs tended to feature younger women. PMID- 8002421 TI - Body image, self-concept, and self-esteem in women who had a mastectomy and either wore an external breast prosthesis or had breast reconstruction and women who had not experienced mastectomy. AB - The perceptions of three groups of women regarding their body image, self concept, total self-image, and self-esteem were compared. The groups included 64 women who had mastectomies and wore external breast prostheses, 31 women who had mastectomies and underwent breast reconstruction, and a control group of 78 women who had not experienced mastectomy. The body image, total self-image, and self esteem mean scores indicated that the prosthesis and reconstruction groups had more positive feelings regarding their bodies than did the control group. There were no significant differences in self-concept among the three groups. These findings challenge a common assumption that mastectomy automatically results in psychiatric morbidity caused by an altered body image and suggest that health professionals should not make assumptions about how a woman will psychologically respond to mastectomy. PMID- 8002420 TI - Depressed mood and self-esteem in young Asian, black, and white women in America. AB - During the last two decades, investigators have explored the relationship between women's life conditions and their mental health. Some have related women's socially disadvantaged status, or their socialization to a traditional feminine role, to depression and low self-esteem. Others have emphasized the consequences of women's roles, or the balance of social demands and resources, on their well being. More recently, feminist scholars have proposed a developmental account of depression. We tested a model comparing the effects of personal resources, social demands and resources, socialization, and women's roles, on self-esteem and depressed mood in young adult Asian, Black, and White women in America. Women who resided in middle-income and racially mixed neighborhoods were interviewed in their homes. Personal resources were indicated by education and income and social resources by unconflicted network size as measured by Barrera's (1981) Arizona Social Support Interview Schedule. Social demands were assessed by conflicted network size as measured by the Barrera scale and by the Positive Life Events and Negative Life Events scales from Norbeck's (1984) revision of the Sarason Life Events Scale. Women's roles included employment, parenting, and partnership with an adult (e.g., marriage). Self-esteem was assessed with the Rosenberg Self Esteem Scale (Rosenberg, 1965) and depressed mood with the Center for Epidemiologic Studies Depression scale (Radloff, 1977). Although models for Asian, Black, and White women differed, social network and social demands as well as personal resources were common to each group as predictors of self-esteem and depression. PMID- 8002422 TI - Rheumatoid arthritis and older women: economics tell only part of the story. AB - The triad of age, gender, and disabling chronic illness sets the stage for increased dependence and deprivation in later life. Women are three times more likely than men to be diagnosed with rheumatoid arthritis (RA). As a prototype of a chronic illness, RA affects all dimensions of a woman's life, usually beginning with physical function, which results in loss of work, social, and recreational activities. Because women incur 40% more chronic illness and live longer than men do, they require more health care and supportive services as they age. Women typically earn less money during their working lives than do men and are more likely to be economically impoverished in old age. Research is needed to identify the multidimensional impact of RA on older women and to explore treatment, life style, and work options that will help younger cohorts of women prepare for their economic needs in old age. PMID- 8002423 TI - Social vulnerability and reactions to caregiving in daughters and daughters-in law caring for disabled aging parents. AB - Variables that have been conceptually linked with social vulnerability--income, educational level, employment, cessation of work to provide care, marital status, social support, and health--were used to predict four categories of reaction to caregiving in 159 daughters and daughters-in-law caring for their disabled aging parents. Social support, income, and health best predicted negative reactions to caregiving; social support alone best predicted negative reactions to caregiving; social support alone best predicted feelings of family abandonment, impact on health, and impact on schedule. Compared with daughters and daughters-in-law who had not quit work to provide care, those who had quit work were significantly older, had lower incomes and fewer social supports, and were more involved in care. The results suggest that quitting work may be a precursor to social isolation that places the caregiver at increased risk for social vulnerability and negative reaction to caregiving. The implications of the findings for health care policy are discussed. PMID- 8002424 TI - Hobby or job? Mexican female health workers. AB - A critical analysis of the role and status of female health workers in the primary health care service (PHC) of the Secretary of Health in the Federal District of Mexico is presented. Women are key workers in the health service; however, since the creation of the PHC service, women appear to have been kept in low-pay, low-status jobs. Data from questionnaires and in-depth interviews with female health workers in the Federal District illustrate the situation. Female health workers' status is determined by the structure and operation of the PHC system; by family and personal needs; by the cultural context of Mexican society; and by the fact that some female health workers view their job as a hobby, placing family considerations above career enhancement. PMID- 8002425 TI - Determinants and consequences of burnout: a cross-cultural comparison of Canadian and Jordanian nurses. AB - We compared the determinants and consequences of burnout for Canadian (N = 586) and Jordanian (N = 263) registered nurses working in a hospital setting. LISREL 7 software was used to perform a path analysis testing hypothesized relationships between job satisfaction dimensions (supervision, hospital identification, kind of work, amount of work, physical work conditions, rewards, and career future) and burnout and intention to quit. For both Canadian and Jordanian nurses, kind of work, amount of work, and career future were important determinants of burnout. Career future and burnout (emotional exhaustion) were associated with intention to quit on the basis of the highly similar results across the two samples, we propose that a universal theoretical model of the determinants and consequences of burnout among nurses may be plausible. PMID- 8002426 TI - Women's experiences of repetitively contracting sexually transmitted diseases. AB - Our purpose in conducting this qualitative, descriptive research was to explore and describe women's experiences of repetitively contracting sexually transmitted diseases (STDs). Ten open-ended, semistructured, in-depth interviews with 8 women, along with stories and anecdotes from one author's clinical practice, provided data. Thematic analysis was used to generate themes important to the women. Themes included the power and significance of heterosexual relationships, female powerlessness, the sense that STDs are an inevitable part of a woman's life, stigma, and victimization. The women's explanatory models for the STDs were quite different from those of health care providers evidenced in the professional literature. The findings from this research support the following suggestions for practice: (a) Practitioners and clients should share their explanatory models to work toward safe sexual behavior, and (b) practitioners need to scrutinize their practices to make sure they are not minimizing the risks of STDs. PMID- 8002427 TI - Nutrient intake of women runners and nonrunners. AB - The nutrient intakes of women who ran at different levels of intensity and the relationship between nutrient intake and ovulatory disturbances were studied. Ninety-five women, including sedentary non-runners (n = 16), low-level runners (n = 27), medium-level runners (n = 29), and high-level runners (n = 23), completed data for a 3-day nutritional assessment. The high-level runners met the Food and Nutrition Board's Recommended Daily Allowances (RDAs) for all 17 nutrients examined, with the exception of calcium. The other groups of women failed to meet RDAs for iron, carbohydrate, and fiber. In general, the women in the study reported healthier diets than did women in a general national survey of nutrient intake conducted in 1985. Eighty-two of the women reported luteinizing hormone level data that were accurate enough to indicate ovulatory functioning; of these women, 30 had ovulatory disturbances. There was no relationship between ovulatory disturbance and nutrient intake; however, 5 amenorrheic women reported a significantly lower nutrient density intake of fat and higher intake of carbohydrate, fiber, and vitamin A than did the nonamenorrheic women. PMID- 8002428 TI - Reasons for employment or non-employment during pregnancy. AB - Although women's pattern of employment during pregnancy has markedly changed in the last 30 years, no research has explored the basis of contemporary women's decision making regarding employment during pregnancy. Conceptualizing pregnancy within a life span developmental perspective of adulthood, we used descriptive statistics and content analysis on data from 210 pregnant women to identify factors that influence employment decisions during pregnancy. Intrinsic reasons for working during pregnancy included self-actualization, escape from home, employment identity, and interpersonal contact. Extrinsic reasons for working included money, financial obligations, and employment setting compatibility. Intrinsic reasons for not working during pregnancy included pregnancy-related limitations, home identity, complexity, and family responsibilities. Extrinsic reasons for not working included financial juggle, job availability, and employment setting incompatibility. The results form a basis for anticipatory guidance recommendations for pregnant women. PMID- 8002429 TI - De Madres a Madres: women building community coalitions for health. AB - How one group of Hispanic women in Houston, Texas, built community coalitions for primary health care is chronicled from the perspectives of the women. We describe how they formed partnerships with community businesses, health and social service agencies, schools, and churches to develop an outreach network that enables pregnant women to obtain early prenatal care. These women's steps in coalition building are related to feminist theory, with an emphasis on group decision making, shared power for the empowerment of all, and the creation of an environment in which individual worth and dignity are enhanced and risk taking is encouraged and supported. PMID- 8002430 TI - Caregiver education: feminist or male model? AB - Most nurses have become aware that they work in patriarchal organizations and understand how oppressive and destructive this is to their career and their work. Few nurses recognize that this same male model dominates many nursing education programs, even those designed, delivered, and controlled by nurses. A study was undertaken to determine the learning needs of critical care nurses in Atlantic Canada and identify obstacles that prevented them from meeting their needs. The findings and the subsequent development of an education program are described. The findings are related to feminist values and feminist-based models of education that seem to be congruent with women's needs. PMID- 8002431 TI - Women with HIV and their burden of caring. AB - It is argued that the survival time of women with AIDS is connected to these women's values and beliefs about health and AIDS, which in turn affect how they care for themselves and others. Moreover, their values and beliefs result from the interrelationship between economic conditions and cultural and social norms. Consequently, women's experience of HIV infection is affected by both their inferior role and status in society and the lack of acknowledgement of HIV and AIDS as women's health issues. This situation has the fatal consequence that women with AIDS have a shorter survival time than do men with AIDS. PMID- 8002432 TI - Worries and worriers in Thailand. AB - How the health and well-being of families in northern Thailand might be gendered and class linked was assessed. First, ethnographic data were gathered to contextualize and elaborate the local meanings of the indigenous concepts kaan khit maak, "thinking-a-lot," and kaan khit maak kern pai, "thinking-too-much." What informants were thinking a lot about was assessed. The health implications of the concept of "thinking-too-much" were then evaluated in 318 middle-aged women and their 24-year-old children (147 daughters and 154 sons) using the Symptoms of Stress Inventory (SOSI). Findings from the SOSI complemented those from fieldwork, demonstrating that both worrying and symptoms of stress were sex linked as well as associated with poverty and with life cycle stage. It is recommended that educational programs to promote khwaan khit pen, the "ability to think", among the disadvantaged of society be resumed. PMID- 8002433 TI - A case study of an abused older woman. AB - Because little is known about elder abuse, it is difficult to propose strategies for primary prevention or to select the most efficacious strategies to deal with abuse. Intervening is also complicated by personal and professional values that often have their origin in one's own family. Elder abuse is a complex challenge to health professionals, making assessment, diagnosis, treatment, and evaluation difficult. Using a case study approach, we illustrate these complexities, describe the dynamics, and apply a decision-making model to the management of a case of abuse. Theoretical research and background information are woven into the discussion of the case to explain further the dynamics. PMID- 8002434 TI - Beyond couvade: pregnancy symptoms in couples with a history of infertility. AB - Thirty-six couples with a history of infertility reported their physical, positive emotional, and negative emotional symptoms during pregnancy. The women experienced more physical symptoms than did the men. Both the men and women experienced second-trimester decreases in negative emotional symptoms and third trimester increases in negative emotional symptoms. The women's physical symptoms also showed a second-trimester dip. Each symptom type was correlated for husbands and wives, but only 6 husbands showed evidence of couvade syndrome by exhibiting exact correspondence with their wives' symptoms. Symptom attunement appears to be a better term than couvade for most infertile men's experiences of pregnancy. PMID- 8002435 TI - Sociocultural and physiological correlates of cigarette smoking in women. AB - Cigarette smoking is a major modifiable risk factor for cancer and coronary heart disease and the chief avoidable cause of death in the United States. Over the past few decades, the prevalence of cigarette smoking among males has significantly decreased. However, the same significant decrease has not been seen among women. Researchers have identified sociocultural factors and physiological correlates associated with women's cigarette smoking. It is essential that health care professionals understand the findings of research on women's smoking if they wish to identify and counsel women at risk and to define directions for future research. PMID- 8002436 TI - The efficacy of SeaBands for the control of nausea and vomiting in pregnancy. AB - Twenty-seven pregnant women (5-22 weeks gestation) participated in a study to determine the efficacy of SeaBands for the control of nausea and vomiting in pregnancy (NVP). NVP was reduced by 50% for these women. SeaBands are more effective if applied early in the symptom experience; less if applied late. SeaBands have considerable potential for a drug-free and noninvasive approach to control NVP. PMID- 8002437 TI - Pay equity for nurses: comparable worth and gender neutrality. PMID- 8002438 TI - Risk identification of abused women participating in a women, infants, and children program. AB - Demographic characteristics, social and health risk factors, and responses to open-ended questions regarding health and abuse experiences were analyzed in a study of women participants in a Women, Infants, and Children supplemental food program at a mid-western county health department. Of the 400 respondents, 124 had experienced physical abuse according to the Partner Abuse Scale: Physical (PASPH) for determining physical abuse (Hudson, 1990). Quantitative and qualitative procedures were applied to the data. A trimmed model indicated that the best predictors of PASPH score were self-perceived abuse and number of medical/health conditions. Implications for service and program development include strategies for ongoing assessment, intervention, and evaluation to detect and to address physical and nonphysical assault. Epidemiological investigation and follow-up are recommended for health conditions discovered as prevalent in this population. PMID- 8002439 TI - Interaction of forage level and monensin in diets for feedlot cattle on growth performance and digestive function. AB - A feedlot growth-performance trial and a metabolism trial were conducted to evaluate the interaction of forage level (10 vs 20%) and monensin (0 vs 28 mg/kg, air-dry basis) on utilization of a steam-flaked corn-based finishing diet. There were no treatment interactions (P > .10) on feedlot cattle growth performance or site and extent of digestion of OM, ADF, N, and starch. Monensin supplementation did not influence (P > .10) ADG, DM intake, feed efficiency, estimated NE value of the diet, or ruminal and total tract digestibility of OM, ADF, and starch. Monensin decreased (14.5%, P < .10) passage of microbial N to the small intestine and ruminal digestion of feed N (10.4%, P < .05). Ruminal pH tended to be slightly lower (1.9%, P < .10) with monensin supplementation. Monensin did not affect (P > .10) ruminal molar proportions of acetate and butyrate. There was an interaction between forage level and monensin on ruminal molar proportions of propionate. With the low-forage diet, molar proportions of propionate were 9.4% higher with monensin supplementation. In contrast, with the high-forage diet ruminal molar proportions of propionate were 5.5% lower with supplemental monensin. Monensin did not affect (P > .10) estimates of methane production. Decreasing the forage in the diet from 20 to 10% increased ADG (10.8%, P < .10), feed efficiency (11.6%, P < .01), and diet NEg (11.3%, P < .05). Ruminal digestibility of ADF, OM, and starch were not affected (P > .10) by forage level.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8002440 TI - Evaluation of machine, technician, and interpreter effects on ultrasonic measures of backfat and longissimus muscle area in beef cattle. AB - Before slaughter, 44 Hereford-sired steers were measured ultrasonically for backfat (UFAT) and longissimus muscle area (ULMA) between the 12th and 13th ribs by three technicians (TECH) using two different machines (MACH) on two consecutive days (DAY). Each TECH interpreted (INT) his own images in addition to other TECH images. The absolute values of the difference between the 2 DAY's ultrasound measurements for ULMA (magnitude of LMAR) and UFAT (magnitude of FATR) were analyzed with a model including fixed effects of MACH and TECH with a random effect of steer and all interactions. For both magnitude of LMAR and magnitude of FATR, MACH x TECH was significant (P < .10). Correlations between the 2 DAY's measurements ranged from .36 to .90 and .69 to .90 for ULMA and UFAT, respectively. Simple statistics to quickly evaluate TECH and MACH were developed. Root mean squared errors (RMSE) and error standard deviations (ESD) between repeated measurements ranged from 3.89 to 11.32 and 3.93 to 11.34 cm2 for ULMA and .12 to .20 cm and .12 to .20 cm for UFAT, respectively. For accuracy, the absolute values of the difference between the ultrasound and carcass measurement for fat (magnitude of FATD) and longissimus muscle area (magnitude of LMAD) were analyzed with a model accounting for fixed effects of DAY, TECH, and MACH and a random effect of steer with all higher-order interactions. For magnitude of LMAD, TECH x MACH was a significant source of variation (P < .001). Also, a similar model was fit that included the fixed effects of TECH, MACH, and INT and a random effect of steer with all interactions. The MACH x INT interaction was found to be significant for magnitude of LMAD (P < .05). From this research, TECH and MACH differences do exist. Ultrasound is a valid means of measuring carcass traits in live steers if appropriate personnel and equipment are selected. PMID- 8002442 TI - Genetic parameters for litter size of different parities in Duroc, Landrace, and large white sows. AB - Univariate and multivariate analyses were performed for litter size born alive and at 21 d in Duroc, Landrace, and Large White sows raised in southern Brazil. Variance and covariance components were estimated for first, second, and third parities, and for different sets of parities using DFREML under animal models with direct and maternal genetic effects. Additive direct genetic variances were different for breeds and for parities within breeds. Most estimates of heritability of direct effects were higher than the average value of .10 reported in the literature, and were two to five times the size of their standard errors, indicating that opportunities for genetic improvement of litter size in these breeds may be greater than assumed on the basis of previous reports. Maternal additive genetic variances were higher in second than in first or third parities, but were significant only for Large White sows. Genetic correlations for all breeds were high between first and third, and between second and third parities, but were low, in the range of .32 and .48, between first and second parities. For this reason, multiple-trait genetic evaluation of animals for litter size should be used to estimate breeding values when first and later parity records are involved. PMID- 8002441 TI - Optimum particle size of corn and hard and soft sorghum for nursery pigs. AB - A total of 240 weanling pigs (22 d of age and 5.3 kg average BW) were used to determine the effects of particle size of corn and two sorghum hybrids on diet processing, growth performance, apparent digestibility of nutrients, and morphology of the stomach and intestines in weanling pigs. Treatments were corn, hard endosperm sorghum, and soft endosperm sorghum milled to particle sizes (geometric mean) of 900, 700, 500, and 300 microns, in a 3 x 4 factorial arrangement. All diets were pelleted and the pigs were allowed to consume feed and water on an ad libitum basis. As particle size was reduced, production rate (tons/hour) decreased and energy required to mill (kilowatt hours/ton) increased. Corn required more energy to mill and had a lower production rate than the sorghums. For d 0 to 14, ADG and gain/feed increased linearly (P < .009 and P < .002, respectively) as particle size was decreased to 300 microns. However, there was a grain source x particle size interaction; pigs fed corn responded to particle size reduction more than pigs fed the sorghums (P < .04). For d 0 to 35, pigs fed diets with corn grew 23% faster and were 6% more efficient (P < .001) than pigs fed diets with sorghum. Gain/feed responded quadratically to reduction of particle size (P < .01), with maximum gain/feed at 500 microns for all grains. Lowest cost of gain (including milling and ingredient costs) was achieved at 500 to 700 microns for corn and 500 microns for the hard and soft sorghums. These data suggest that response to reducing particle size is greatest during the first 2 wk postweaning and that optimal particle size for corn and sorghums increases with age of nursery pigs. PMID- 8002444 TI - Optimal contemporary group structure to maximize genetic progress through genetic evaluation of swine. AB - Accuracies of sire EPD were calculated for a typical growth trait and a typical maternal trait for alternative contemporary group structures. For a given family size (number of progeny tested for a sire in a contemporary group), accuracy increased as the number of sires increased and as the number of contemporary groups increased. An exponential equation was found to best predict accuracy from the number of sires and groups. Partial derivatives can be used to determine the optimal number of sires and groups for a given economic situation (fixed number of animals tested per group). It is recommended that progeny of at least two sires be represented in each contemporary group, but having more than five sires does not effectively increase accuracy further. Accuracy increases with a larger herd size, as more sires and more groups of pigs are tested. When the number of litters that can be tested is at its limit, accuracy is maximized with a small number of sires, and progeny divided among several contemporary groups. However, accuracy is only part of the herd's genetic improvement. Selection decisions must be made to avoid inbreeding, which can be a problem, particularly in small herds. PMID- 8002443 TI - Method R variance components procedure: application on the simple breeding value model. AB - An algorithm for estimating variance components (Method R) based on the linear regression coefficient (R) of recent (more accurate) on previous (less accurate) individual genetic predictions is presented. The previous prediction is obtained by analyzing a subsample of the whole data set. First raw moment of R equals 1 regardless of the distribution of observations and predictions. A condition such as the use of inappropriate variance components ratio (VC) can cause this regression to deviate from its expectation. If the computed R (Rc) is greater than 1, then VC ratio has been underestimated, and if Rc is less than 1, then VC ratio has been overestimated. Several iterations are performed, changing the VC ratio at each iteration, until Rc approximately equal to 1. When an Rc is obtained that is acceptably close to 1 (precision is reached), then the appropriate VC has been used. Method R does not require computation of the inverse of the coefficient matrix and has desirable properties of convergence, precision, and computing feasibility. Additional sampling variance in the estimate of VC is expected due to the requirement of taking a subsample of the entire data set to obtain the lower accuracy predictions. This sampling variance is shown to be small for simulated datasets of size n = 10,000 with no selection. PMID- 8002445 TI - Wisconsin's "stale calf" issue and a study designed to resolve some of the animal welfare concerns. AB - A unique law (Act 201) requiring livestock markets to place an identifying mark on calves up to 90 kg each time they are sold went into effect in Wisconsin in 1993. The intent of the law is to reduce the number of times calves are resold and hence become "stale." The original proponents of the law proposed that calves be ear-notched each time they are sold. Ear notching, however, was resisted by Wisconsin regulatory agencies partly because of fear of an adverse public reaction. These authors then conducted a study to determine the approximate amount of discomfort experienced by young Holstein calves during ear notching. Six 2-mo-old Holstein calves were used to determine heart rate and behavioral responses to a standard "V" pig ear notcher (6 mm wide x 14 mm deep) applied between the tip and halfway down the dorsal edge of the left ear. Five other calves were given 30 s of access to a rubber nipple to provide a comparison to a desirable stimulus. Ear notching only elicited a mild startle response that lasted 1 to 2 s followed by resumption of normal behavior. The calves presented with the nipple suckled or butted the nipple for the full 30 s. The mean heart rate for the 30-s period in which treatments occurred was 95 +/- 4.8 bpm and 110 +/- 5.8 bpm for the notched and suckled calves, respectively, and was not influenced by treatments (P = .50).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8002446 TI - Relationship of horn fly to face fly infestation in beef cattle. AB - Horn fly and face fly counts (n = 394) taken on 194 beef cows representing seven breed groups were used to determine the effects of horn fly and face fly counts. Breed groups included were Angus (ANI and ANII), Chianina (CA), Charolais (CH), Hereford (HH), Polled Hereford (PH), and Red Poll (RP). The breed group designated ANI consisted of small-framed cows. Total horn fly and total face fly counts were determined weekly on each cow beginning in May and ending in late October or early November in a 3-yr (1988-90) study. Face flies were not counted on the ANI and ANII breed groups in 1988. All fly counts were taken when cows were grazing Ozark upland native grass pastures with only containment fences separating breeding groups. No insecticides were used in the study. Data for analysis were the mean annual horn fly and face fly counts (averaged across weeks), spring weight and fall weights, gain/day between spring and fall weights, and skin surface area in the spring (SSAS) and fall (SSAF) for each cow. Relationships among measurements were examined by correlation and regression procedures. Horn fly count was correlated (P < .05) with face fly count, spring weight, gain/day, and SSAS (.23, .11, -.25, and .12, respectively). Correlations of horn fly count with fall weight and SSAF were non-significant. Horn fly count, breed, and the breed x horn fly count interaction were significant (P < .05) for the face fly regression.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8002447 TI - Effects of serum and insulin-like growth factor I on protein degradation and protease gene expression in rat L8 myotubes. AB - We examined the effects of horse and fetal bovine sera and insulin-like growth factor I (IGF-I) on proteolysis and protease gene expression in rat L8 skeletal myotube cultures. Protein degradation was measured as release of radioactive trichloroacetic acid (TCA)-soluble materials from intracellular proteins prelabeled with [3H]tyrosine. Horse serum and fetal bovine serum inhibited (P < .05) protein degradation by 19.7 and 8.1%, respectively. The IGF-I at 200 ng/mL inhibited protein degradation by 14% (P < .01) over a 6-h measurement period. To study the regulation of proteolysis by IGF-I, we evaluated its effects on protease mRNA and alpha-tubulin mRNA concentrations by Northern blot analysis. Proteases under investigation included cathepsins B and D, proteasome C2 subunit, and m-calpain. The IGF-I had no effect (P > .05) on cathepsin B and D gene expression but slightly increased (P < .05) m-calpain and alpha-tubulin mRNA concentrations. Proteasome mRNA concentration was reduced (P < .05) by IGF-I treatment. The changes in proteasome mRNA levels paralleled the IGF-I-dependent alterations in proteolysis. These observations suggest that effects of IGF-I on muscle protein degradation may be mediated by the specific down-regulation of proteasomal subunit mRNAs. PMID- 8002448 TI - Endocrine responses and body composition changes during feed restriction and realimentation in young bulls. AB - Changes in serum metabolic hormones, carcass composition, and body weight gains were examined in 21 Angus bulls (9 mo old) subjected to feed restriction and realimentation. They were allotted to three feeding regimens: 1) control (CON); 2) restricted (REST); and 3) realimented (REAL). The CON group was fed 3.2% of their body weight; the REST group was fed 1.5%. The REAL group was fed the restricted diet (1.5% BW) for 84 d then fed the control diet (3.2% BW) until slaughter. The CON and REAL groups were slaughtered at approximately 400 kg and the REST group at 346 kg. For the experiment, average daily gains (kg/d) were different (P < .05) (CON = 1.60; REAL = 1.35; REST = .64). Bulls were bled every 20 min for 6 h on d 14, 70, 98, and 127 of the experiment. Overall carcass characteristics (yield grade, muscle area, marbling) and chemical analysis of 9 10-11 rib sections indicated changes in quantity and percentages of protein and fat commensurate with the dietary intake treatments. The REST group had the least lean and fat (P < .05); the REAL group had less fat than (P < .05) but the same amount of lean (P > .05) as the CON group. Serum GH was higher in the REST than in the CON group (P < .05). In the REAL group, serum GH values rose to a level similar to that of the REST group; realimentation lowered serum GH (P < .05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8002449 TI - The effect of cimaterol on muscle fiber characteristics, capillary supply, and metabolic potentials of longissimus and semitendinosus muscles from young Friesian bulls. AB - The objective of this study was to determine the effect of the beta-adrenergic agonist cimaterol (CIM) on fiber characteristics, capillary supply, and metabolic enzyme activities in muscles of young Friesian bulls. Four pairs of monozygotic twins in each of three live weight groups (WG) were used (initial average live weight [LW]: 162, 299, and 407 kg, respectively). Within each pair, one twin was fed .06 mg of CIM.kg LW-1.d-1 for 90 d. The other twin served as control (C). Needle biopsies were obtained from the longissimus (LM) and semitendinosus (ST) muscles at d 82 to 84 of treatment, and muscle fibers were identified as slow twitch (Type I) or fast-twitch (Type IIA or Type IIB) by the myosin ATPase stain. In LM, the proportion of Type I (C: 24.0%, CIM: 20.4%; P < .07) and Type IIA fibers (C: 24.2%, CIM: 8.6%; P < .001) decreased, whereas the proportion of Type IIB fibers increased (C: 51.7%, CIM: 71.1%; P < .001). Cimaterol increased the cross-sectional area of Type I (P < .02) and Type IIB fibers (P < .001), with no change in Type IIA fibers. Overall, the mean fiber area increased (C: 2,363 microns 2, CIM: 3,934 microns 2; P < .001). The number of capillaries per fiber did not change, but the number of capillaries per square millimeter decreased (P < .001) after CIM treatment. Cimaterol changed metabolic enzyme activities toward lower oxidative capacity of the muscle (lactate dehydrogenase: +22%, hydroxyacyl CoA dehydrogenase: -33%, and citrate synthetase: -34%; all P < .001) and reduced the glycogen content by 25% (P < .01).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8002450 TI - Effects of cooking and shearing methodology on variation in Warner-Bratzler shear force values in beef. AB - Longissimus lumborum between the 13th rib and the 4th lumbar vertebra from 57 steers was obtained at 48 h postmortem, stored at 2 degrees C, and frozen after 7 d postmortem. Consecutive 2.54-cm-thick, paired steaks were used to make the following comparisons: Protocol A) steaks were broiled to 70 degrees C, chilled 24 h at 3 degrees C, cored parallel to fiber orientation, and sheared with a Warner-Bratzler attachment to the Instron and Protocol B) steaks were modified oven-broiled to 65 degrees C, cooled 30 min at 23 degrees C, cored perpendicular to the steak surface, and sheared with a Warner-Bratzler shear machine. Each of the four differences in protocol was subsequently compared one at a time with paired steaks. Protocol A resulted in higher (P < .05) shear force values than Protocol B (6.29 vs 3.60 kg). Neither shearing instrument nor cooling condition contributed to the difference (P > .05) in shear values. However, parallel vs perpendicular core orientation (6.31 vs 4.51 kg, respectively) and broil to 70 degrees C vs modified-oven broil to 65 degrees C cooking method (6.37 vs 5.31 kg, respectively) increased (P < .05) shear force values. Total variance (6.2 vs 1.2 kg2) and the proportion of variance in shear value attributed among animals was greater (P < .05) for Protocol A than for Protocol B (70.0 vs 44.5%). These data indicate that Protocol A resulted in greater animal differences in shear values, and thus was more discriminating than Protocol B.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8002451 TI - Colostral milk fat percentage and pig performance are enhanced by feeding the leucine metabolite beta-hydroxy-beta-methyl butyrate to sows. AB - Three trials were conducted to test whether feeding the leucine metabolite beta hydroxy-beta-methyl butyrate (HMB) would increase fat content of sows' milk and pig weight gain. All sows received a basal diet and were assigned at random to receive either 2 g of CaCO3/d (control) or 2 g of Ca(HMB)2/d (HMB), which was top dressed to the basal diet. Treatment began 3 to 4 d before farrowing. In Trials 1, 2, and 3 there were 4, 19, and 11 pairs of sows, respectively. In a combined analysis that included all three trials, milk fat at d 1 was increased by 41% (P = .01) and pig weight at d 21 was increased by 7% (P = .01) for sows fed diets containing HMB compared with sows fed control diets. Sows fed HMB lost more backfat (P = .03); however, sows receiving HMB had more (P < .05) backfat depth at farrowing than control sows. At weaning there was no difference in backfat depth between the treatment groups. Sows fed HMB tended to consume less feed (P = .07) than control sows. In Trials 2 and 3, data were collected on the subsequent reproductive cycles of the sows. A combined analysis of the data revealed no differences in sow performance when sows previously fed the diet containing HMB were compared with sows previously fed the control diet. In conclusion, beta hydroxy-beta-methyl butyrate, when fed to sows at 2 g/d, resulted in an increase in fat percentage of sow's milk and pig performance.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8002452 TI - An assessment of dietary folic acid levels during gestation and lactation on reproductive and lactational performance of sows: a cooperative study. S-145 Committee on Nutritional Systems for Swine to Increase Reproductive Efficiency. AB - Crossbred female swine (n = 393) were used in a multiparity study at five experiment stations to evaluate the effects of dietary supplementation of folic acid (FA) on serum folates status and reproductive performance. The dietary treatments were a corn-soybean meal basal diet (calculated FA, .34 ppm) supplemented with 0, 1, 2, or 4 ppm FA. Experimental diets were fed continuously from a minimum of 21 d before first mating throughout the entire study. At one station, blood samples for radioimmunoassay determination of serum folates concentration were collected by vena cava puncture at mating, d 55 of gestation, d 110 of gestation, and at weaning. Stage of reproduction and dietary FA supplementation affected (P < .005) serum folates concentrations. Serum folates declined from mating to d 55, remained low at d 110, and returned to higher levels at weaning. Linear increases (P < .001) in serum folates with increasing level of dietary FA were observed at each reproductive stage. Over the course of the study, reproductive performance criteria including total pigs born, live pigs at birth and d 21, and individual pig and litter weight at birth and d 21 were not affected (P > .10) by inclusion of FA in the diet. The number of days postweaning to estrus also was not affected by FA treatment. Under the conditions of this experiment, increasing level of FA in the diet had a pronounced effect in attenuating decreased serum folates concentration during gestation but was without benefit to reproductive performance. PMID- 8002453 TI - Plasma concentrations of prolactin, glucose, insulin, urea nitrogen, and total amino acids in stallions after ingestion of feed or gastric administration of feed components. AB - Concentrations of prolactin, glucose, insulin, urea N, and total amino acids in plasma of stallions after ingestion of pelleted feed were compared to those after direct gastric administration of water, NaCl, egg albumin, or corn starch (Exp. 1) or water, egg albumin, hydrolyzed casein (Amicase), or a mixture of indispensable amino acids (Exp. 2). Stallions were fed once daily (75% pellet and 25% hay) at 1500 for 30 d. On d 22, 24, 26, 28, and 30, blood samples were collected every 30 min from 1 h before through 4 h after treatment, which occurred at 1100. In Exp. 1, there was a positive secretory response for prolactin (P = .013) only after the meal. Positive glucose and insulin responses were observed after the meal (P < .055) and after gastric administration of corn starch (P < .001). Total amino acids increased (P = .008) only after the meal. In Exp. 2, a positive prolactin response (P < .001) occurred after the meal and a negative response (P = .023) after administration of water; administration of Amicase increased (P = .061) prolactin concentrations after a 2.5-h delay. Positive responses were observed for glucose, insulin, and total amino acids after the meal (P < .001) and after administration of Amicase or the amino acid mixture (P < .026). Positive urea N responses were observed after administration of Amicase and the amino acid mixture (P < .001).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8002454 TI - Efficacy of magnesium-L-ascorbyl-2-phosphate as a vitamin C source for weanling and growing-finishing swine. AB - Two experiments were conducted, one with weanling pigs (n = 288) and the second with grower-finisher swine (n = 216), to evaluate the efficacy of dietary vitamin C on various performance and serum measurements. Magnesium-L-ascorbyl-2-phosphate (46% L-ascorbic acid) served as the vitamin C source and was incorporated at dietary levels of 0, 50, or 500 ppm in both experiments. Pigs were allotted by sex, weight, and litter to randomized complete block designs. The nursery trial was conducted at four time periods and contained 12 replicates, whereas the grower-finisher experiment was over four time periods and contained nine replicates. Blood samples were collected initially from nine randomly selected pigs in both experiments, and from each pig within each pen at 2 and 5 wk postweaning, and at the 4- and 8-wk period in the grower-finisher trial. A killed Salmonella typhinurium bacterin was injected i.m. into starter pigs at 2 wk postweaning and at wk 4 and 6 in grower-finisher pigs. Hemagglutination titers were evaluated at 5 wk with the nursery pigs and at the 8-wk period with the grower-finisher swine. At the end of the grower-finisher trial, liver and kidney tissue were analyzed for ascorbate. Starter pigs grew faster (P < .05) and had improved gain:feed ratios (P < .05) when vitamin C was provided during the first 2 wk postweaning, but not during the latter 3-wk period. There was no improvement in pig gain or feed efficiency to vitamin C supplementation during any phase of the grower-finisher period.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8002455 TI - Effect of level of dietary neutral detergent fiber on ileal apparent digestibility and ileal nitrogen losses in pigs. AB - A study was conducted with 20 barrows (average BW 25 kg) to determine the effect of various levels of neutral detergent fiber (NDF) in the diet on the apparent ileal nutrient digestibility and ileal diaminopimelic acid (DAPA) content, and consequently on the amount of ileal endogenous nitrogen. The pigs were fitted with a post-valvular T-cecal cannula. They were fed .8 kg/d of a corn starch based semisynthetic diet formulated to contain equal amounts of protein and starch and 0, 60, 120, or 180 g of purified NDF/kg of diet, included at the expense of glucose. The purified NDF (pNDF) was isolated from wheat bran using an incubation procedure with pancreatin. Ileal digestibility of NDF was approximately 17% and was independent of the pNDF level in the diet. By increasing the amount of pNDF in the diets, apparent ileal digestibilities of dry matter (DM), nitrogen (N), neutral detergent insoluble N (NDF-N), and ash decreased linearly (P < .05). The DAPA content of the ileal digesta (g/d) was not affected by the percentage of pNDF in the diets. Calculation of the ileal bacterial N excretion indicated that more than 50% of the ileal N was of bacterial origin. With increased percentage of dietary pNDF, both endogenous and exogenous N in ileal chyme were linearly increased (P < .05). Thus, an increase in the dietary fiber content leads to a decreased apparent ileal protein digestibility due to increased ileal losses of both endogenous and exogenous protein. PMID- 8002456 TI - Effects of dietary energy intake by gilts and heat stress from days 3 to 24 or 30 after mating on embryo survival and nitrogen and energy balance. AB - Bred gilts were used in two experiments (n = 140) to study the interaction and main effects of dietary energy intake and heat stress on embryo survival and nitrogen (N) and energy balance from d 3 to slaughter on d 30 (Exp. 1) or d 24 (Exp. 2) after mating. In both experiments, the ME treatments were 5.4 or 8.1 Mcal of ME/(gilt.d). Temperatures were either a constant thermoneutral of 23 +/- 1 degrees C or a heat stress regimen, making four treatments in a 2 x 2 factorial arrangement. Gilts were allotted directly to one of the treatments on d 3 after mating. In Exp. 1, the 24-h cyclic heat stress regimen consisted of an increase from 25 degrees C at 0800 to 34 degrees C at 1400, 34 degrees C from 1400 to 1700, then a decline to 25 degrees C at 2000, with 25 degrees C until 0800. In Exp. 2, heat stress was constant at 33 +/- 1 degrees C. No energy x temperature treatment interactions occurred (P > .2 to .8) for the variables measured in Exp. 1 and 2. Heat stress reduced (P < .05 or .01) diet and ME intake/day, ME retained/day, and ME/GE compared with the thermoneutral controls in Exp. 1 and 2. Heat stress reduced (P < .05) N digestibility in Exp. 1 and reduced (P < .01) N retained/day and N retention/N intake in Exp. 2. Rectal temperature and respiration rate were increased (P < .01) by heat stress in Exp. 1 and 2.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8002457 TI - A microplate-based bioassay system for measuring porcine serum mitogenic activity. AB - A bioassay system was developed to measure porcine serum mitogenic activity, which is an indicator of growth factor activity. A MTT [3-(4,5-dimethylthiazol-2 yl)-2,5-diphenyl-tetrazoliumbromide++ +] cell proliferation assay was used to monitor cell growth. In comparison with electronic cell counting, this bioassay system is sensitive, economical, and semi-automatic. A non-fusing myoblast cell line, BC3H1, was used, making it possible to increase seeding density and thus improve precision. The assay was carried out in 96-well microplates with automatic reading and data processing by a computer-controlled ELISA reader. Results were highly correlated with Kotts' method. This assay system is of potential value in studying growth regulation in pigs. PMID- 8002458 TI - The role of feed consumption and feed efficiency in copper-stimulated growth. AB - Two experiments were conducted to study the role of feed intake and feed efficiency in Cu-stimulated growth of weanling pigs. In Exp. 1, 42 pigs were randomly assigned into three treatments: 1) control: ad libitum access to a corn soybean meal-dried whey basal diet; 2) ad libitum/Cu: ad libitum access to the basal diet supplemented with 215 ppm of Cu; or 3) pair-fed/Cu: pair-fed the Cu supplemented diet to the level of the control. Over the 14-d experiment, the ad libitum/Cu pigs had greater (P < .05) ADG and ADFI than the control pigs. The pair-fed/Cu group had an intermediate ADG. Gain:feed (GF) was not significantly affected by treatments but tended to be improved in the pair-fed/Cu pigs. Feeding copper increased (P < .05) the concentration of Cu in the serum, liver, and brain. Also, feeding Cu increased (P < .05) serum mitogenic activity and growth hormone mRNA concentrations for both feeding methods. In Exp. 2, a 2 x 2 x 2 factorial arrangement of treatments with two levels of Cu (15 vs 200 ppm), two levels of feeding (ad libitum vs restricted [85% of the ad libitum]), and two sources of Cu (Cu sulfate vs Cu lysine) was used in a 24-d experiment involving 96 pigs. Feeding copper increased (P < .05) ADG and GF. The magnitude of the Cu stimulated growth was reduced by restricted feeding (Cu level x feeding level interaction; P < .05). The ADFI was greater (P < .05) for the pigs fed high dietary Cu only during d 1 to 6. Pigs fed Cu lysine had greater ADG and ADFI than those fed Cu sulfate (P < .05); the benefit in ADG from Cu lysine was reduced by restricted feeding (Cu source x feeding level interaction, P < .05). High dietary Cu stimulated (P < .05) serum mitogenic activity; the stimulation was greater for Cu lysine than for Cu sulfate. Feeding Cu numerically increased GH mRNA concentration. Restricted feeding reduced overall serum mitogenic activity (P < .05), but the response to high dietary Cu and Cu lysine was still evident. In summary, Cu-stimulated growth was largely dependent on a simultaneous increase in feed intake, but there were some improvements in GF. The influence of Cu on serum mitogenic activity was independent of feed intake or growth in both experiments, which indicates a direct action of Cu on the growth regulatory system. PMID- 8002460 TI - Porcine somatotropic regulation of thymic weight, thymosin beta 4, and insulin like growth factors in lean and obese swine. AB - Experiment 1 involved genetically lean and obese gilts and barrows injected for 42 d with 0, 2, or 4 mg/d of porcine somatotropin (pST; n = 96). Blood was collected at 0, 6, and 24 h after the initial pST injection and thereafter every 2 wk. Experiment 2 involved lean and obese gilts and barrows (n = 48) that were administered implants that released 0, 2, or 4 mg/d of pST for 42 d. Blood was collected at d 0, 7, 14, 28, and 42 of the study. Thymic weights and a final blood sample were collected at the end of the 42-d trial. Thymic weights increased (P < .01) with dose of pST in injected and implanted animals. Thymosin beta 4 increased (P < .05) in a pST dose-dependent manner in injected and implanted animals, but concentrations were increased more in implanted animals. Concentrations of thymosin beta 4 decreased or reached a plateau in gilts but continued to increase in barrows to the end of the trial. Thymosin alpha 1 concentrations were increased (P < .01) in barrows compared with gilts, but the concentrations were not related to dose of pST. Concentrations of pST in injected animals increased (P < .01) within 6 h after injection and had returned to basal concentrations by 24 h after injection. Concentrations of pST in implanted animals were dose-dependent (P < .05) and remained increased throughout the trial. Concentrations of IGF-I and -II were pST-dependent (P < .01) and increased throughout the trial period. Outside of the pST dose relationships, temporal changes in thymosin beta 4 were not highly related to changes in pST, IGF-I, or IGF-II. The pST dose-related increases in thymic weights and thymosin beta 4 concentrations are consistent with pST stimulation of the immune function in conjunction with overall increases of growth and efficiency of live weight gain in swine. PMID- 8002459 TI - Stimulation of growth by intravenous injection of copper in weanling pigs. AB - This study was conducted to examine whether Cu could exert its growth-promoting effect when injected, rather than being fed, and thus bypass the gastrointestinal tract. In two 18-d experiments, pigs were injected every 2 d with a Cu histidinate or histidine solution. Amounts of Cu injected were calculated to simulate varying absorption rates in pigs fed 250 ppm of dietary Cu. In Exp. 1, 44 pigs were randomly assigned to four groups of 11 pigs each. Pigs were injected with four levels of Cu histidinate (0, 5, 10, and 15% estimated apparent absorption coefficients based on calculated feed intake). Average daily gain responded quadratically (P < .05) to levels of Cu histidinate; maximum growth was seen in the 5% group. At d 6, serum mitogenic activity also exhibited a similar quadratic response (P < .05). In Exp. 2, estimated Cu absorptions of 0, 2, 4, 6, and 8% were tested. Forty-five pigs were randomly assigned to five groups of nine pigs each and injected as in Exp. 1. Both ADG and serum mitogenic activity displayed a quadratic response (P < .05); the maximum response was seen in the 4% group. Liver Cu content, superoxide dismutase activity, and serum Cu concentrations were linearly increased (P < .05) with increasing dosage of Cu in both Exp. 1 and 2. Also, brain Cu content linearly increased (P < .05) with increasing dosage of Cu in both Exp. 1 and 2. Also, brain Cu hormone mRNA concentrations in Exp. 2 were not significantly influenced by treatments.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8002461 TI - Nutritional manipulation of growth and metabolic and reproductive status in prepubertal gilts. AB - Reproductive status, metabolic state, and carcass composition were compared in prepubertal littermate gilts of 85 kg BW and identical ages after allocation to one of two feeding regimens at 75 kg, either twice-daily feeding to appetite up to 85 kg and then maintenance feeding until slaughter (Group 85AR) or an initial period of maintenance feeding at 75 kg and then feeding to appetite to reach 85 kg (Group 85RA). Other littermates were studied at the start of treatment (Group 75C) and after the initial period of feeding to appetite (Group 85A) or maintenance feeding (Group 75R). In the absence of differences in backfat depth or longissimus muscle area, Group 85RA gilts showed increased follicular development (P < .001) compared with their feed-restricted Group 85AR littermates. Plasma LH (P < .001) and FSH (P < .02) responses to an LHRH challenge differed between these same groups. Feed restriction reduced preprandial glucose, postprandial cortisol, and insulin (P < .05), total plasma IGF-I, and basal and postprandial free triiodothyronine (T3; all P < .001) at all stages of the experiment. Postprandial insulin, pre- (P < .001) and postprandial free T3, and plasma IGF-I (P < .001) increased in response to refeeding (Group 75R vs 85RA). These data indicate that changes in metabolic status can mediate short-term nutritional effects on reproductive function, in the absence of changes in age, weight, and widely used indices of body composition, and also establish the short-term, feed-restricted, prepubertal gilt as an effective model for studying the mechanisms mediating nutrition-reproduction interactions. PMID- 8002462 TI - Recombinant bovine somatotropin does not improve superovulatory response in sheep. AB - Although treatment of heifers and ewes with recombinant bovine somatotropin (rbST) does not increase ovulation rate, data for heifers indicate that the number of small antral follicles is approximately doubled. Accordingly, the objectives of this study were to determine whether 1) treatment of ewes with rbST would increase the number of small antral follicles, thereby increasing the number of follicles that could potentially respond to superovulation treatment, and 2) superovulatory responses could be improved in ewes with "synchronized" populations of follicles. Twenty-four ewes were divided into four groups: control, control+rbST, hypothalamic-pituitary stalk disconnected (HPD), and HPD+rbST. Beginning on d 5 of the estrous cycle, ewes were injected once daily for 13 d with either rbST (3 mg) or saline. The superovulatory regimen consisted of a single dose of PMSG followed by twice-daily injections of FSH for four consecutive days. After ovariectomy, ovulation sites and follicles were counted. Twice-daily blood samples were assayed for somatotropin (ST) and IGF-I. The concentrations of ST in rbST-treated ewes were greater (P < .05) than those in controls. Treatment with rbST increased (P < .05) the mean serum concentration of IGF-I in control but not in HPD ewes. There was no increase in ovulation rate or number of small antral follicles in response to rbST. Synchronizing follicle populations also failed to increase ovulation rate or reduce variability of response. We conclude that supplementation with rbST and synchronization of follicles does not increase the superovulatory response in sheep. PMID- 8002463 TI - Fertility of range beef bulls grouped according to presence or absence of heparin binding proteins in sperm membranes and seminal fluid. AB - Trials were performed to determine the relationship of heparin-binding proteins (HBP) to fertility of bulls. Red Angus (142), Santa Gertrudis (59), Gelbvieh (59), and Santa Gertrudis x Gelbvieh (40) bulls were identified according to the presence or absence of the greatest affinity HBP (HBP-B5) on sperm membranes and in seminal fluid. Nine to 20 bulls with the same HBP-B5 profiles were assigned to pastures with Santa Gertrudis cows at a ratio of 1 bull:25 cows. Fertility for Group 1 (80 bulls with HBP-B5 in sperm membranes but undetectable HBP-B5 in seminal fluid, in six pastures) was 82% pregnant of 1,692 cows. Group 2 bulls (48 bulls with HBP-B5 detectable in seminal fluid and in sperm membranes, in four pastures) impregnated 67% of 919 cows. Fertility for Group 3 (37 bulls with HBP B5 in seminal fluid but undetectable HBP-B5 in the sperm membranes, in three pastures) and Group 4 (56 bulls with undetectable HBP-B5 in seminal fluid and sperm, in four pastures) was 63% pregnant of 747 and 1,208 cows, respectively. Group 1 had an average of 17% greater fertility compared with Groups 2, 3, and 4 (P < .05). In conclusion, groups with the greatest affinity HBP-B5 in sperm membranes but not in seminal fluid had greater fertility than did groups with other HBP-B5 profiles. PMID- 8002464 TI - Technical note: a radioimmunoassay for porcine retinol binding protein. AB - This report describes a RIA for porcine retinol binding protein (RBP) that has been validated for measurement of RBP concentrations as low as 10 ng/mL in serum, follicular fluid, uterine flushings, allantoic fluid, and endometrial and uterine tissue culture medium. The increasing displacement of porcine [125I]RBP resulting from decreasing dilutions of each sample was parallel to the standard curve, and exogenous RBP added to samples was accurately measured with the assay. To examine specificity, 1-mL samples of serum, uterine flushings, follicular fluid, and allantoic fluid were subjected to G-100 Sephadex chromatography, and the fractions were assayed for RBP with the RIA and for fluorescence, which detects retinol bound to RBP. The RBP measured with the RIA and the fluorescent fractions coeluted. Samples of uterine flushings in which RBP was measured using immunoblotting and densitometry were also assayed with the RIA. The measurements using the two methods were correlated (r = .84, P < .01). These results are evidence that the assay is specific for RBP. The limit of detection of the assay was .46 ng. The RIA should facilitate the study of RBP function and the control of its secretion by various tissues in pigs. PMID- 8002465 TI - Influence of moisture content of forage diets on intake and digestion by sheep. AB - To determine the effect of forage moisture content on intake and digestion kinetics in sheep, a metabolism trial was conducted using 16 mature wethers (44 kg BW) in a completely randomized design. Forage was harvested at two maturities in early spring from a naturalized pasture composed of temperate grass and legume species. Herbage was harvested at either 8 (early) or 16 cm (late) in height and fed after freezing (high-moisture) or as a dried hay. Intakes of DM (grams/[kilogram BW.75.day]), NDF, ADF, and CP (grams/day) (P < .05) and coefficients for DM, NDF, and ADF digestibilities were greater (P < .01) for hay than for high-moisture forage. Mean particulate retention times (MRT) were shorter (P < .05) for high-moisture forage (23.3 h) than for hay (30.7 h) diets. Early-harvested forages had shorter (P < .05) MRT values (23.9 h) than late-cut forages (30.1 h). Fractional passage rates of 1-mm nylon particles of specific gravity (SG) .90, 1.14, and 1.32 through the alimentary tract were influenced by moisture content of the forage (P < .10) and were faster for frozen forages and increased (P < .01) with an increase in SG. Nitrogen retention was greater (P < .01) for the hay than for the high-moisture forage. In situ DM digestion rates, determined using four ruminally fistulated wethers, showed no differences (P = .67) among forages. The results of this study indicate that differences in digestibilities between hays and high-moisture forages are most likely due to differences in digesta passage rates. PMID- 8002466 TI - Influence of non-fibrous carbohydrate and degradable intake protein on fermentation by ruminal microorganisms in continuous culture. AB - Four continuous culture fermenters were used in a 4 x 4 Latin square design to evaluate the effects of dietary non-fibrous carbohydrate (NFC) and ruminally degradable intake protein (DIP) on fermentation by ruminal microorganisms. Four diets, arranged in a 2 x 2 factorial, were formulated to contain either 25 or 40% NFC and 50 or 70% of dietary CP as DIP. Dietary DM contained 32% corn silage, 20% alfalfa-grass hay, and 48% concentrate. Solvent-extracted or lignosulfonate treated soybean meal were used to alter DIP and contributed 40% of dietary CP. Corn or soybean hulls were included at 28% of dietary DM to alter NFC levels. Percentage of true OM digestion was similar (P > .05) among diets but NDF and total nonstructural carbohydrate digestion were inversely related depending on NFC content of the diet. Amylolytic bacterial concentrations (cells/milliliter) were lower (P = .03) in fermenters supplied with 25% NFC diets, resulting in less (P = .0001) total nonstructural carbohydrate digestion. Cellulolytic concentrations were similar (P > .05) among diets despite an increase (P = .002) in NDF digestion with 25% NFC diets. Total viable bacterial concentrations tended to decrease (P = .11) with 50% DIP diets, inducing a decline (P = .03) in total VFA production (millimoles/day). Reduced degradation of CP in 50% DIP diets (P = .008) increased outflow of total amino acid (P = .07) and individual outflows (P < .05) of glutamic acid, aspartic acid, arginine, histidine, and lysine. Few interactions occurred for the parameters measured despite the controlled nature of the fermentation in the current experiment. The preponderance of significant main effects illustrates that ruminal fermentation may not be improved by synchronization of energy and N release but may more likely be limited by either energy or N alone. PMID- 8002467 TI - Effect of frequency of supplementation and protein concentration in supplements on performance and digestion characteristics of beef cattle consuming low-quality forages. AB - Three experiments evaluated whether effects of altered frequency of supplementation on forage use and cow performance depended on supplement CP concentration and (or) grain type when fed to cattle eating low-quality forages. All experiments included supplementation frequency (daily = 7x; three times weekly = 3x) as one factor in a factorialized arrangement of treatments. In Exp. 1 and 2, the second factor was supplement CP concentration (10, 20, 30, and 40% CP), altered by changing the ratio of soybean meal to sorghum grain in supplements. Supplements were fed at 13.9 and 14.1 kg of DM/wk for Exp. 1 and 2, respectively. In Exp. 3, the second factor was supplement grain type (sorghum grain or corn) and supplements containing 21% CP were fed at 14.8 kg of DM/wk. In Exp. 1, eight ruminally fistulated steers (456 kg) consumed wheat straw ad libitum. Pregnant beef cows grazing dormant tallgrass prairie were used in Exp. 2 (475 kg; n = 128) and 3 (504 kg; n = 120). In Exp. 1, reducing supplementation frequency decreased (P < .01) straw intake but increased (P < or = .03) DM and NDF digestion. As CP concentration in supplements increased, straw DMI (P = .06) increased quadratically, whereas DM and NDF digestion increased linearly (P < .01). In Exp. 2, increasing CP concentration in supplements enhanced cows' ability to maintain BW and condition up to calving, with decreasing magnitude of difference between treatments at higher CP concentrations (P < .01). Increasing CP in supplements fed to the dams linearly (P = .05) increased calf weaning weight in Exp. 2. In Exp. 2 and 3, reducing supplementation frequency increased (P < or = .02) winter weight loss through calving. Grain type did not significantly affect most performance variables. In summary, response to supplementation frequency was not dependent on supplement CP concentration or grain type. Daily supplementation maximized forage intake and cow performance, although the magnitude of performance differences was not large. PMID- 8002468 TI - The influence of restricted feeding on site and extent of digestion and flow of nitrogenous compounds to the duodenum in steers. AB - The effects of restricted feeding on site and extent of digestion, flow of N containing compounds to the duodenum, and ruminal metabolism were determined. In Trial 1, corn silage-based diets were fed at one of three intakes to three ruminally and duodenally fistulated steers (420 +/- 4.4 kg BW) in a repeated 3 x 3 Latin square experiment. Feeding levels were 100% of ad libitum intake, 90% of ad libitum intake, and 80% of ad libitum intake. Site of digestion was not affected by restricted feeding; however, extent of DM, NDF, and apparent N digestion were increased (P < .03) 2.8, 4.1, and 6.2 percentage units for each 1 kg restriction in DM intake. Restricted feeding increased (P < .06) ruminal pH and ammonia concentrations, decreased (P < .05) ruminal liquid dilution rate, and had no major effects on bacterial concentrations. In Trial 2, all-concentrate diets based on whole shelled corn were fed at 100, 90, or 80% of ad libitum intake to six ruminally and duodenally fistulated steers (440 +/- 4.1 kg BW) in a replicated 3 x 3 Latin square experiment. Restricted feeding increased (P < .06) apparent ruminal DM digestion; however, true ruminal OM digestibility was not affected. Extent of apparent N digestion increased 3.0 percentage units for each 1-kg restriction in DMI. Ruminal pH was not affected by restricted feeding; however, ruminal ammonia concentrations increased (P < .06) and ruminal liquid dilution rate decreased (P < .04) with restricted feeding. In both Trials, total N flow to the duodenum was approximately 100% of N intake for the 80% of ad libitum intake. Flow of N exceeded N intake in a linear (P < .01) manner as DMI increased. Decreases in duodenal N flow when intake was restricted resulted from decreases (P < .01) in bacterial N flowing to the duodenum, and also in decreases (P < .01) in non-ammonia, non-bacterial N flow when whole shelled corn-based diets were fed. We concluded that restrictions in digestible energy intake are less than the DM restriction when corn silage-based diets are fed but are equal to the DM restriction when whole shelled corn-based diets are fed. Also, restricted feeding strategies reduce the flow of N to the duodenum from both bacterial and feed origins. PMID- 8002469 TI - Effects of restricted feeding of growing steers on performance, carcass characteristics, and composition. AB - Two experiments were conducted to determine the effects of restricted feeding on performance, carcass characteristics, and composition. In Trial 1, 36 individually penned steer calves (280 +/- 13 kg BW) were fed all-concentrate diets at intake levels of ad libitum and 90 and 80% of ad libitum. Trial 2 used 36 individually penned steer calves (298 +/- 14 kg BW) fed corn silage-based growing diets for 84 d followed by 91% concentrate finishing diets. Intakes were as described for Trial 1. Compared with steers with ad libitum intake, ADG was reduced (P < .005) .15 and .25 kg for steers fed 90 and 80% of ad libitum intake, respectively, in Trial 1. In Trial 2, growing phase ADG was reduced (P < .005) .15 and .24 kg for the 90 and 80% of ad libitum feed intake, respectively. Finishing phase ADG was reduced (P < .005) .12 and .21 kg for the 90 and 80% of ad libitum intake, respectively. Feed efficiency was not affected by intake when all-concentrate diets were fed in Trial 1, or when a corn silage-based diet was fed in the growing phase of Trial 2. During the finishing phase of Trial 2, feed efficiency was increased when intake was restricted. Carcass quality grade and 12th rib backfat were reduced (P < .04) with decreases in daily feed intake when all-concentrate diets were fed. However, no effect on carcass characteristics was observed in Trial 2. Liver and heart weights were not affected by daily feed intake. Serum triiodothyronine (T3) concentrations tended (P = .11) to decrease for cattle receiving restricted intakes of all-concentrate diets and were decreased (P < .04) with intake restriction in Trial 2. Carcass fat content was reduced (P < .02), whereas carcass protein and water were increased (P < .06) with reductions in daily feed intake in both trials. We concluded that restrictedly feeding growing-finishing steer calves does not decrease feed efficiency and actually may improve feed efficiency. Restrictedly fed steers had reduced maintenance requirements, and lean tissue accretion represented a greater percentage of their total gain. PMID- 8002470 TI - Effects of chemically treated, recycled newsprint on feed intake and nutrient digestibility by growing lambs. AB - In situ experiments and two lamb digestion trials were conducted to evaluate the effects of chemically treating recycled newsprint (NP). Treatment of NP with 2% HCl (percentage of NP DM) followed by autoclaving for 4 h was most efficacious and was used in an in vivo digestion trial with 25 ram and wether lambs in a randomized complete block design (RCB). On a DM basis treatment diets were: 1) control, 95% alfalfa hay (AH); 2) 75% AH, 20% HCl-treated NP (HCl-NP); 3) 55% AH, 40% HCl-NP; 4) 75% AH, 20% untreated NP; and 5) 55% AH, 40% untreated NP on a DM basis. Lambs fed Treatments 2 and 3 had ad libitum DMI (1,043 and 1,036 g/d, respectively) similar to the DMI of those fed the control treatment (1,024 g/d); however, lambs fed Treatments 4 and 5 had lower (P < .05) ad libitum DMI (578 and 426 g/d, respectively) than lambs fed Treatments 1, 2, and 3. Apparent DM digestibilities were lower (P < .05) by lambs consuming Treatments 2, 3, 4, and 5 (52.6, 44.5, 52.0, and 48.2%, respectively) than by those consuming Treatment 1 (60.7%). Apparent OM, CP, NDF, and ADF digestibilities followed trends similar to DM. In the second digestion trial, 15 ram and wether lambs were used in a RCB to compare Treatments 1, 2, and 3. For this second digestion study, NP was treated with 4% HCl (percentage of NP DM), autoclaved for 4 h, and diets were fed at 2% of BW. As in Trial 1, apparent nutrient digestibilities decreased (P < .05) with increasing amounts of HCl-NP. Our results suggest that HCl-NP can be fed to sheep at 40% of the diet without a decrease in DMI; however, apparent nutrient digestibility decreases with increasing levels of HCl-NP. PMID- 8002471 TI - Multidisciplinary approach to evaluating welfare of veal calves in commercial facilities. AB - Due to pending legislation and public concerns, a multidisciplinary approach was designed to investigate the welfare of special-fed veal calves in commercial veal facilities. Concerns included housing conditions, dietary regimens, management practices, and behavioral aspects imposed on special-fed calves. Four categories of parameters including environment and housing, nutrition, health and stress, and behavior provided a broad base of evaluating veal systems. Observations and samples were collected on 550 Holstein bull calves located in 10 commercial veal facilities. Each facility was visited to collect data during wk 0 (week of arrival of the calves), 2, 4, 8, 12, and 16. Nine facilities used individual stalls 48 to 55 cm in width with tethers attached to the front of the stalls. One facility housed 30 calves in group pens after obtaining calves at 8 wk of age. Ammonia, carbon monoxide, and hydrogen sulfide gas did not exceed the permissible limit for humans in any facility. All facilities exceeded the 2-foot-candle recommendation for lighting. The average daily gain of calves was .85 kg during wk 0 to 8 and 1.18 kg during wk 8 to 16. Dietary iron levels decreased from 209 ppm at wk 0 to 32 ppm at wk 16. At 16 wk, 25% of calves were marginally anemic and 10% clinically anemic. Overall mortality was 4.2%. Stress indices such as plasma cortisol concentrations or neutrophil to lymphocyte ratios declined as calves approached market weight. In either pens or stalls, calves spent approximately 25 and 75% of time in standing and lying positions, respectively.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8002472 TI - Rapid degradation of the triazinone herbicide metamitron by a Rhodococcus sp. isolated from treated soil. AB - Seven bacterial isolates which degraded the herbicide metamitron (3-methyl-4 amino-6-phenyl-1,2,4-triazin-5-one) were obtained from field-enhanced soil by liquid enrichment culture. All isolates appeared to be identical and a representative, 0246b, was identified as a Rhodococcus sp. by cell wall and fatty acid analyses. This isolate degraded metamitron as the sole source of carbon within 24 h at 25 degrees C and this is the first report of a bacterium capable of growing with metamitron as the sole source of carbon. Metamitron was degraded less rapidly when it was the sole source of both carbon and nitrogen. The rate and extent of degradation was affected by the presence and type of additional sources of carbon and nitrogen in the culture medium. In studies with [14C] phenyl-labelled metamitron Rhodococcus sp. 0246b partly mineralized the phenyl ring. PMID- 8002473 TI - Differential elimination of enteric bacteria by protists in a freshwater system. AB - The short-term (1 h) and long-term (3 d) elimination of low and high densities of five enteric bacteria, Klebsiella pneumoniae, Aeromonas hydrophila, Escherichia coli, Enterococcus faecalis and Staphylococcus epidermidis, by flagellate and ciliate protists were measured in a freshwater system. In addition, the two processes, ingestion and digestion, which cause the disappearance of those enteric bacteria as time passes, were quantified. The results showed that the elimination of these enteric bacteria by protists depends on their initial density, which confirms that the lower the bacterial density the more difficult is their elimination. On the other hand, the short-term and long-term elimination rates of each enteric bacteria were different, and moreover, the order of priority for elimination in the two cases was not the same. Escherichia coli showed the highest elimination rate in short-term experiments, while Aer. hydrophila disappeared at highest rates in long-term experiments. This different order of priority in the elimination rates and the different digestion rates on the five enteric bacteria by phagotrophic protists indicated that the elimination in time is very much influenced by the digestive capacity on each enteric bacteria of those protists. Thus, the low digestion rates of Ent. faecalis and Staph. epidermidis by flagellates and ciliates as well as their low disappearance percentages in the long-term experiments confirm that enteric Gram-positive bacteria are eliminated from the aquatic systems at lower rates, because their digestion is difficult. PMID- 8002474 TI - HM17, a new polyene antifungal antibiotic produced by a new strain of Spirillospora. AB - An antifungal antibiotic (HM17) was obtained from a new isolate classified to the genus Spirillospora on the basis of its chemical and morphological properties. On solid media this antibiotic strongly inhibited the growth of strains of Fusarium oxysporum formae speciales albedinis, Botrytis cinerea, Gaeumaniomyces graminis and several other fungi known to be plant and human pathogens. Antifungal activity in culture collection strains of Spirillospora has not so far been reported. The u.v. absorption spectrum and physico-chemical characteristics place HM17 in the methylpentaene sub-group of polyene macrolides. HM17 is different from other known methylpentaenes. This is the first report of polyene production by a Spirillospora. PMID- 8002475 TI - The immediate bactericidal effect of lactic acid on meat-borne pathogens. AB - The kinetics of the bactericidal effect of lactic acid decontamination (LAD) on meat-borne pathogens (Salmonella spp., Campylobacter jejuni and Listeria monocytogenes) was studied in an in-vitro model. The bactericidal effect was greatest on organisms in the lactic acid film that replaced the natural fluid on the meat surface during LAD. A stepwise increase in pH from 2.6 to 3.5 and 4.0 progressively reduced the bactericidal effect of decontamination. For treatment with 2% lactic acid for 30-90 s at 21 degrees C, the immediate death of Salmonella spp. decreased from about 0.5-2 log10 cfu at pH 2.6 to an insignificant level at pH 4.0. The immediate death for Camp. jejuni decreased from 2.6 to > 5.3 at pH 2.6 to 0.3-1.0 at pH 4.0. The decrease in bactericidal effect with increasing pH could, however, be countered by an increase in the temperature from 21 degrees C to 37 degrees C. It is suggested that 2% LAD at 37 degrees C for 30-90 s is suitable for elimination of salmonellas on meat but not for L. monocytogenes. Decontamination with 1% lactic acid at pH 3.0 and 21 degrees C for at least 30 s was effective for Camp. jejuni. Mesophilic Enterobacteriaceae were reliable indicators of the LAD-induced bactericidal effect on Salmonella spp. and Camp. jejuni. PMID- 8002476 TI - An investigation of enumeration and DNA partitioning in Bacillus subtilis L-form bacteria. AB - Cell numbers of two morphogenic forms of Bacillus subtilis (the cell-walled parental and the derived stable cell wall-deficient L-form) have been compared by two methods: DNA hybridization (i.e. deduced genome numbers) and viable cell counts (i.e. number of colony-forming units (cfu)). The DNA hybridization method was shown to be a reliable and reproducible method for estimating genome numbers. Comparison of different L-form populations showed that the two methods of enumeration gave different values, with the deduced genome numbers much higher (by several orders of magnitude) than cell numbers deduced from viable cell counts. In contrast, when a culture of the cell-walled form was enumerated, the discrepancy between the two methods was low (by a factor of about 6) The combination of a high number of L-form genomes detected by DNA hybridization and a relatively low number of cfu was thought to be a consequence of a diminished co ordination between the DNA replication and cell division processes in L-form bacteria. This suggestion was further substantiated by assessing the stability of plasmid pPL608 in a transformed B. subtilis L-form cell line, where even in the presence of continued kanamycin selection, 25% of the population lost kanamycin resistance. The results are discussed with particular reference to cell division in cell wall-deficient, stable L-form bacteria. PMID- 8002477 TI - Characterization of beta-glucosidase activity in yeasts of oenological origin. AB - Three hundred and seventeen strains representing 20 species of yeasts were screened for the presence of beta-glucosidase activity. All of the strains of the species Debaryomyces castellii, Deb. hansenii, Deb. polymorphus, Kloeckera apiculata and Hansenula anomala showed beta-glucosidase activity, but only one of 153 strains of Saccharomyces cerevisiae. The other species behaved differently, depending upon the strain. The strains that hydrolysed arbutin were checked to localize the beta-glucosidase activity. A strain of Deb. hansenii exhibited the highest exocellular activity and some wall-bound and intracellular activity. The beta-glucosidase synthesis from this yeast was enhanced by aerobic conditions of growth, was repressed by high glucose concentration (9%) and occurred during exponential growth. The optimum conditions for enzymatic preparations of Deb. hansenii were between pH 4.0 and 5.0 and 40 degrees C. A high concentration of ethanol and glucose did not reduce the enzymatic activity. The enzymatic preparations of Deb. hansenii released monoterpenols and other alcohols from a grape glycoside extract. PMID- 8002478 TI - Degradation and utilization of forage hemicellulose by rumen bacteria, singly in coculture or added sequentially. AB - Procedures for sequential addition experiments were developed to study the mechanisms involved in the synergistic and inhibitory interactions observed in forage hemicellulose digestion by rumen bacterial cocultures. One organism was allowed to ferment a forage substrate, the culture tube was sterilized and then inoculated with a second organism. No differences were found in the extent of degradation or utilization between fermentations sterilized by oxidation or heat, and based on ease of handling, heat was used in all subsequent experiments. Studies were conducted with Fibrobacter succinogenes A3c, Ruminococcus flavefaciens B34b and Prevotella ruminicola H2b, singly and in all possible combinations. Results from the sequential addition studies substantiated earlier suggestions that the increase observed in hemicellulose utilization results from initial solubilization of the hemicellulose from the forage by the non-utilizer and subsequent utilization of subsequent utilization of this solubilized polysaccharide by the utilizing, but non-degrading organism. PMID- 8002479 TI - Staphylococcal growth and enterotoxins (A-D) and thermonuclease synthesis in the presence of dehydrated garlic. AB - The inhibition of Staphylococcus aureus growth and enterotoxin and thermonuclease production by various concentrations of garlic (Allium sativum) was studied in BHI broth. The growth of Staph. aureus was inhibited by dehydrated garlic at levels of 1.5% (w/v) and over. Enterotoxins A, B and C1 were only detectable in broth containing < 1% of garlic while enterotoxin D was produced at a level of 2%. Garlic also inhibited thermonuclease (TNAse) production, complete inhibition being observed at levels > or = 1.5%. TNAse was not always detected when enterotoxin was present. PMID- 8002480 TI - A red pigment synthesized by an Aspergillus parasiticus mutant as a possible new intermediate in the aflatoxin biosynthetic pathway. AB - The isolation of a red pigment from an Aspergillus parasiticus mutant obtained by 366 nm u.v. light treatment of A. parasiticus NRRL 2999 is described. Studies of conversion in aflatoxin B1 and G1 suggest that the red pigment could be a possible new intermediate in the aflatoxin biosynthetic pathway not described to date, and this has been verified by studies in gas chromatography/mass spectrometry. The solubility and stability characteristics under refrigeration storage, and the influence of the temperature and the pH on its production by the A. parasiticus mutant were also studied. It grew best at 30 degrees C and pH 6. The red pigment was most soluble in ethyl acetate. The results obtained in water are emphasized where there was high stability. PMID- 8002481 TI - Random amplification of polymorphic bacterial DNA: evaluation of 11 oligonucleotides and application to food contaminated with Listeria monocytogenes. AB - The polymerase chain reaction was used to obtain randomly-amplified polymorphic DNA (RAPD) profiles from Listeria spp. and enterobacteria. Eleven different oligonucleotides were evaluated. Only one, HR4 (19mer), generated reproducible and specific profiles for Listeria spp., while results for enterobacteria were controversial. A total of 57 different Listeria strains were subjected to the RAPD analysis and 27 different profiles were recognized. RAPD typing allowed strains of the same serotype to be distinguished but the same profile was obtained from different serotypes of L. monocytogenes in three cases and in one case two different serotypes of L. innocua yielded the same profile. RAPD-typing with HR4 allowed L. monocytogenes contamination in several food outlets to be traced back to a food processing plant. In additional experiments, the general utility of this RAPD system in typing Yersinia enterocolitica, verotoxigenic Escherichia coli and Salmonella enteritidis was evaluated. PMID- 8002482 TI - The microaerophily and photosensitivity of Propionibacterium acnes. AB - The effect of oxygen on the in vitro propagation of Propionibacterium acnes was investigated under defined culture conditions. This micro-organism is the predominant bacterial resident within the pilosebaceous follicles of sebum-rich areas of human skin. The organism was grown in continuous culture in defined synthetic medium with glucose as the main carbon-energy source at various air saturation concentrations and in the presence and absence of light. Steady state continuous cultures were achieved at very low oxygen tensions in the presence of light, and at higher levels of oxygen when non-illuminated. Culture biomass yields were higher than those of anaerobic cultures. Bacterial cells were inactivated in the presence of light at high oxygen concentrations because of photosensitization reactions involving excess oxygen and microbial porphyrin species. PMID- 8002483 TI - A note: comparison of different homogenization procedures for detecting Campylobacter spp. in sewage sludge. AB - Crude sewage sludge contains Campylobacter spp. in a concentration of 10(1)-10(3) cfu 100 ml-1 on average. Because large variations in the number of bacteria are seen when samples are examined in parallel, we attempted to improve the detection method. Seeded sewage sludge samples were homogenized by a high-speed blender, ultrasonic bath and ultrasonic bar. Bacterial counts were determined by the MPN method in triplicate. The recovery rate was < 10%. Subsequently, sludge samples without artificial contamination were also examined. The bacterial counts varied considerably, as seen earlier. In order to enhance the detection rate of campylobacters homogenization times and frequencies were increased, samples were diluted prior to treatment and pre-enriched in non-selective broth or supplemented with detergent. None of the methods applied proved satisfactory. The bacterial counts achieved with all methods varied greatly, with minimum and maximum values lying at least two orders of magnitude apart. PMID- 8002484 TI - Effects of GABA receptor blockage on the respiratory response to hypoxia in sedated newborn piglets. AB - Brain gamma-aminobutyric acid (GABA) levels increase during hypoxia, which may modulate the ventilatory response to hypoxia. To test the possibility that the depressed neonatal ventilatory response to hypoxia may be related to increased central nervous system GABA activity, 26 sedated spontaneously breathing newborn piglets (age 5 +/- 1 day, wt 1.7 +/- 0.4 kg) were studied. Minute ventilation (VE), oxygen consumption, heart rate, arterial blood pressure, and arterial blood gases were measured in room air and after 1, 5, and 10 min of hypoxia (inspired O2 fraction 0.10) before drug intervention. Immediately after these measurements, an infusion of saline or the GABA alpha-receptor blocker (bicuculline, 0.3 mg/kg iv) or beta-receptor blocker (CGP-35348, 100-300 mg/kg iv) was administered while animals were hypoxic. All measurements were repeated at 1, 5, and 10 min after initiation of the drug infusion. Basal VE was similar among groups. During hypoxia, VE increased significantly in the animals that received either a GABA alpha- or beta-receptor blocker but not in those receiving saline. Changes in arterial Po2, oxygen consumption, heart rate, and arterial blood pressure were similar among groups before and after saline or GABA antagonist infusion. These results suggest that the decrease in ventilation during the biphasic ventilatory response to hypoxia in the neonatal piglet is in part mediated through the depressant effect of GABA on the central nervous system. PMID- 8002485 TI - Proposed nomenclature for quantifying subdivisions of the bronchial wall. AB - There is increasing interest in the structural components of the airway wall because of the airway remodeling that is observed in conditions such as asthma and chronic obstructive pulmonary disease and because of their contribution to changes in airway mechanics. This interest has stimulated several groups to make morphometric measurements on airway cross sections, and their results have been reported using a variety of nomenclature. We propose the adoption of a standard system of nomenclature that is based on accepted terms for subdivisions of the airway wall and has been agreed to by several groups working in this field. PMID- 8002486 TI - Pressure transmission across the respiratory system at raised lung volumes in infants. AB - Forced expiratory flow-volume (FEFV) curves can be generated from end-tidal inspiration in infants with use of an inflatable jacket. We have developed a technique to raise lung volume in the infant before generation of FEFV curves. Measurements of pressure transmission to the airway opening by use of static maneuvers have shown no change with increasing lung volume above end-tidal inspiration. The aim of this study was to determine, under dynamic conditions (i.e., during rapid thoracic compression), whether the efficiency of pressure transmission across the chest wall is altered by raising lung volume above the tidal range. Dynamic pressure transmission (Ptx,dyn) was measured in five infants (age 6-17 mo). Jacket pressure (Pj), esophageal pressure, and volume were measured throughout passive and FEFV curves at lung volumes set by 10, 15, and 20 cmH2O preset pressure. The group mean Ptx,dyn was 37 +/- 6% (SE) of Pj at end tidal inspiration, and no change was seen with further increases in lung volume. However, a mean decrease in Ptx,dyn of 42% was evident throughout the tidal volume range (i.e., from end-tidal inspiration to end expiration). Isovolume static pressure transmission (Ptx,st) was measured in three of the five infants by inflation of the jacket in a stepwise manner with the airway closed. Measurements were made at end-tidal inspiration and lung volumes at 10, 15, and 20 cmH2O preset pressure. Resulting changes in Pj, esophageal pressure, and airway opening pressure were compared using linear regressions to determine Ptx,st.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8002487 TI - 31P-MRS and simultaneous quantification of dynamic human quadriceps exercise in a whole body MR scanner. AB - An ergometer for dynamic quadriceps exercise in a magnetic resonance (MR) scanner is physiologically validated, and its technical aspects are presented. The reproducibility of heart rate (HR), O2 consumption (VO2), and power (P) during two graded exercises on the MR ergometer was good (n = 8). Graded exercises on the MR ergometer and on a cycle ergometer (n = 17) were similar with respect to the regression lines between 1) HR and VO2 and 2) HR and P; also peak P did not differ significantly (280 +/- 37 and 298 +/- 41 W, respectively). Peak HR (171 +/ 14 and 184 +/- 15 beats/min, respectively), peak VO2 (3.00 +/- 0.51 and 3.54 +/- 0.44 l/min, respectively), and the slope of the regression line between P and VO2 were lower for MR exercise (P < 0.01). During quadriceps exercise in an MR scanner (n = 12), peak P was 64-143 W for the right leg, with corresponding inorganic phosphate-to-phosphocreatine ratios of 0.85-7.2. It is concluded that continuous noninvasive assessment of energy metabolism with 31P-MR spectroscopy and quantification of power output can be performed simultaneously during dynamic quadriceps exercise, without major reduction of the spectral resolution or the signal-to-noise ratio, and that exercise on this MR ergometer currently is the best possible approximation of cycling exercise for MR purposes. PMID- 8002488 TI - Evans blue dye in the assessment of permeability-surface area product in perfused rat lungs. AB - Evans blue dye (EBD) has been used extensively as a marker of extravascular protein leakage. We assessed the utility of EBD as an albumin marker in the measurement of permeability-surface area product (PS) in perfused rat lungs and compared the results with PS values obtained using 125I-labeled albumin. In isolated perfused rat lungs, PS was measured by exposure to a perfusate containing EBD (600 micrograms/ml) and 125I-albumin (I microCi) for exactly 3 min, followed by washout of the intravascular space with fresh perfusate for 6 min. In lungs from normal rats, we found that PS obtained by EBD (PS-EBD) was fivefold higher than PS obtained by 125I-albumin (PS-125I) [1.92 +/- 0.32 (SE) vs. 0.42 +/- 0.03 x 10(-2) cm3.min-1.g-1, P < 0.05]. Similarly, in rats pretreated with Salmonella enteritidis lipopolysaccharide (2 mg/kg iv), PS-EBD was much higher than PS-125I (2.01 +/- 0.30 vs. 0.59 +/- 0.08 x 10(-2) cm3.min 1.g-1, P < 0.01). This discrepancy between PS-EBD and PS-125I was not explained by differences in the amount of free marker in perfusate, because the albumin binding rate for both markers was very high. In addition, prolonged perfusion (40 min) with EBD did not significantly affect pulmonary vasoreactivity or water content in rat lungs. A detailed comparison of the kinetics of lung tissue uptake of EBD followed by parallel uptake of both markers up to 60 min of perfusion.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8002489 TI - Accurate method to study static volume-pressure relationships in small fetal and neonatal animals. AB - We designed an accurate method to study respiratory static volume-pressure relationships in small fetal and neonatal animals on the basis of Archimedes' principle. Our method eliminates the error caused by the compressibility of air (Boyle's law) and is sensitive to a volume change of as little as 1 microliters. Fetal and neonatal rats during the period of rapid lung development from day 19.5 of gestation (term = day 22) to day 3.5 postnatum were studied. The absolute lung volume at a transrespiratory pressure of 30-40 cmH2O increased 28-fold from 0.036 +/- 0.006 (SE) to 0.994 +/- 0.042 ml, the volume per gram of lung increased 14 fold from 0.39 +/- 0.07 to 5.59 +/- 0.66 ml/g, compliance increased 12-fold from 2.3 +/- 0.4 to 27.3 +/- 2.7 microliters/cmH2O, and specific compliance increased 6-fold from 24.9 +/- 4.5 to 152.3 +/- 22.8 microliters.cmH2O-1.g lung-1. This technique, which allowed us to compare changes during late gestation and the early neonatal period in small rodents, can be used to monitor and evaluate pulmonary functional changes after in utero pharmacological therapies in experimentally induced abnormalities such as pulmonary hypoplasia, surfactant deficiency, and congenital diaphragmatic hernia. PMID- 8002490 TI - Reduction of SDH activity in exhausted diaphragm muscle fibers may be an artifact. PMID- 8002491 TI - "Carotid baroreflex control of blood pressure and heart rate in men during dynamic exercise". PMID- 8002492 TI - Myosin isoforms in mammalian skeletal muscle. AB - Skeletal muscles of different mammalian species contain four major myosin heavy chain (MHC) isoforms: the "slow" or beta-MHC and the three "fast" IIa-, IIx-, and IIb-MHCs; and three major myosin light-chain (MLC) isoforms, the "slow" MLC1s and the two "fast" MLC1f and MLC3f. The differential distribution of the MHCs defines four major fiber types containing a single MHC isoform and a number of intermediate hybrid fiber populations containing both beta/slow- and IIa-MHC, IIa and IIx-MHC, or IIx- and IIb-MHC. The IIa-, IIx-, and IIb-MHCs were first detected in neonatal muscles, and their expression in developing and adult muscle is regulated by neural, hormonal, and mechanical factors. The transcriptional mechanisms responsible for the fiber type-specific regulation of MHC and MLC gene expression are not known and are presently being explored by in vivo transfection experiments. The functional role of MHC isoforms has been in part clarified by correlated biochemical-physiological studies on single skinned fibers: these studies, in agreement with results from in vitro motility assays, indicate that both MHC and MLC isoforms determine the maximum velocity of shortening of skeletal muscle fibers. PMID- 8002493 TI - Carotid baroreflex control of blood pressure and heart rate in men during dynamic exercise. AB - The degree of control of blood pressure (BP) and heart rate (HR) by arterial baroreflex during exercise is still controversial. We studied baroreflex control of BP and HR in seven normal young men by a noninvasive procedure employing a neck suction chamber that delivers pulsatile positive and negative pressures to the carotid sinus (CS). Pressures applied to the CS ranged from -80 to +60 Torr in steps of 20 Torr. Pressure stimuli were triggered by electrocardiogram R wave, and each pressure step was maintained for 20 s in a continuous sequence. One baroreflex-response curve was obtained during the last 3 min of each 6-min period of exercise. The four levels of upright (cycle) exercise were 60, 120, 180, and 240 W, the highest requiring approximately 75% of maximal O2 uptake. The sensitivity of the HR baroreflex response assessed by linear regression of HR vs. CS pressure (CSP) did not significantly decrease from rest (-0.09 +/- 0.053 beat/Torr) to 240 W (-0.06 +/- 0.025 beat/Torr). The BP above or below which CSP was increased or decreased by neck collar pressure was significantly increased from rest (76 +/- 6.5 Torr) to 240 W (111.2 +/- 4.0 Torr). The sensitivity of baroreflex response was assessed by linear regression of BP vs. CSP and was not significantly different from rest (-0.29 +/- 0.054 Torr/Torr) up to exercise at 240 W (-0.29 +/- 0.048 Torr/Torr). We conclude that mild to severe exercise does not reduce the gain of the CS reflex below resting values.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8002494 TI - Developmental differences in vascular responses to hypoxia in lungs of rabbits. AB - Our purpose was to determine whether postnatal age and prostaglandins influence the sites of hypoxic vasoconstriction in lungs of rabbits. To do this, we used the micropuncture technique to measure pressures in 20- to 80-microns-diam subpleural arterioles and venules during sequential inflation of lungs of newborn and adult rabbits with normoxic (21% O2-7-10% CO2-69-72% N2) and hypoxic (90-93% N2-7-10% CO2) gas mixtures. Indomethacin (40 micrograms/ml) was added to the perfusate of some lungs of each age group. During hypoxia in untreated lungs of newborn rabbits, both pulmonary arterial and 20- to 80-microns-diam arteriolar pressure increased by 5%, whereas 20- to 80-microns-diam venular pressure remained the same. In contrast, during hypoxia in untreated lungs of adult rabbits, pulmonary arterial pressure increased by 48%, whereas 20- to 80-microns diam arteriolar pressure decreased slightly and 20- to 80-microns-diam venular pressure did not change. Regardless of the presence of indomethacin, location of vessels used for micropuncture, or level of left atrial pressure, pulmonary arterial pressure was the only measured vascular pressure that increased with hypoxia in adult lungs. Thus, in adult lungs, the site of hypoxia-induced vasoconstriction was limited to arteries > 80 microns diam, whereas in newborn lungs the site of hypoxia-induced vasoconstriction included vessels both larger and smaller than 20- to 80-microns-diam arteries. This age-related difference in the sites of hypoxia-induced vasoconstriction was not found in indomethacin treated lungs. PMID- 8002495 TI - Impaired plasma FFA oxidation imposed by extreme CHO deficiency in contracting rat skeletal muscle. AB - The extent to which carbohydrate (CHO) availability affects free fatty acid (FFA) metabolism in contracting skeletal muscle is not well characterized. To study this question, rats were depleted of glycogen by swimming exercise and lard feeding 24 h before perfusion of their isolated hindquarters. After 20 min of preperfusion with a medium containing no glucose, palmitate (600 or 2,000 microM), and [1-14C]palmitate, flow was restricted to one hindlimb, which was electrically stimulated for 2 min to further deplete muscles of glycogen. After 2 min of recovery, glucose was added to the perfusate at final concentrations of 0, 6, or 20 mM, and after another 3 min muscles were stimulated for 30 min. At 6 and 2,000 microM palmitate, glucose uptake after 30 min of stimulation averaged 23.5 +/- 9.3 and 45.9 +/- 10.6 mumol.g-1.h-1 with 6 and 20 mM glucose, respectively. At 6 and 2,000 microM palmitate, palmitate uptake was lower (30-37%, P < 0.05) with 0 than with 6 or 20 mM glucose. At 600 microM palmitate, percent palmitate oxidation was higher (27%, P < 0.05) with 0 than with 6 or 20 mM glucose, resulting in similar total palmitate oxidation with the three glucose concentrations (0.28 +/- 0.01 mumol.g-1.h-1). At 2,000 microM palmitate, percent palmitate oxidation was not significantly different among glucose concentrations, resulting in a significantly lower rate of palmitate oxidation with 0 (0.62 +/- 0.18 mumol.g-1.h-1) than with 6 or 20 mM glucose (0.77 +/- 0.25 and 0.78 +/- 0.20 mumol.g-1.h-1, respectively).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8002496 TI - Nitric oxide-independent response to acetylcholine by terminal arterioles in rat cremaster muscle. AB - The aim of the present study was to establish whether, in terminal arterioles from the rat cremaster, acetylcholine (ACh) elicits nitric oxide (NO)-independent dilation corresponding to the transient ACh-induced endothelium-dependent hyperpolarization described in arteries. For this purpose, the responses of terminal arterioles [mean diam 15.0 +/- 0.4 (SE) microns] were studied by intravital microscopy in rat cremaster muscle. During 15 min of superfusion by 10(-5) M ACh, the response was characterized by an initial maximal dilation (peak time < 3 min) followed by a more sustained dilation that slightly decreased with time. Inhibition of NO synthesis by 2 x 10(-4) M N omega-nitro-L-arginine (L-NNA) significantly reduced, but did not eliminate, both the peak and sustained responses. Simultaneous administration of 2 x 10(-4) M L-NNA and 2 x 10(-5) M mefenamic acid, an inhibitor of prostaglandin synthesis, did not induce a significantly different response from that observed with L-NNA alone. Procaine (10(-3) M), which is known to inhibit completely ACh-induced hyperpolarization in carotid artery, drastically reduced the initial part of the ACh-induced dilation but not the sustained response. Simultaneous administration of procaine and L-NNA almost completely inhibited the peak response to ACh. Similar results were obtained when L-NNA was combined with a superfusion bath containing 20 mM KCl, a concentration known to reduce hyperpolarization in arteries.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8002497 TI - Effects of acute running exercise on whole body insulin action in obese male SHHF/Mcc-facp rats. AB - This study utilized the obese male spontaneously hypertensive heart failure rat (SHHF/Mcc-facp), which has metabolic features very similar to human non-insulin dependent diabetes mellitus. The purpose of this study was to assess the insulin sensitivity and responsiveness of whole body glucose disposal and insulin suppressability of hepatic glucose production with use of the euglycemic hyperinsulinemic clamp procedure in 12- to 15-wk-old SHHF/Mcc-facp rats at rest (OS) and 2.5 h after a single session of acute exercise (OE). Lean male SHHF/Mcc facp rats were sedentary (LS) control animals. At least three clamps producing different insulin-stimulated responses were performed on each animal in a randomized order. At this age the obese animals are normotensive and have not developed congestive heart failure. Compared with LS, OS were significantly hyperglycemic and hyperinsulinemic and insulin sensitivity and responsiveness of whole body glucose uptake and insulin suppressability of hepatic glucose production were significantly decreased. Compared with LS and OS, acute exercise significantly decreased resting plasma glucose but did not alter plasma insulin. Compared with OS, acute exercise significantly increased the insulin responsiveness of whole body glucose disposal but did not affect the sensitivity of whole body glucose disposal or insulin suppressability of hepatic glucose production. Compared with LS, however, acute exercise did not "normalize" the insulin responsiveness of whole body glucose disposal. Thus a single acute exercise session improves but does not normalize whole body insulin resistance in the SHHF/Mcc-facp rat. PMID- 8002498 TI - Tissue oxygen and carbon dioxide stores and breath-hold diving in humans. AB - Alveolar gas exchange was studied in 11 submerged subjects during and after 75-s breath holds with or without a transient increase of ambient pressure to 3 ATA (20 msw). During surface breath holds (SBH), cardiac index fell to 73% of eupneic control but was partially restored at depth to 88% of control during breath-hold dives (BHD). O2 uptake fell to 84% of control during SBH and was restored to control level during BHD. The turnover of O2 stores was much slower during SBH than during the ensuing recovery. Carbon dioxide store dynamics were markedly slowed after BHD. We conclude that SBH and BHD are associated with large shifts in tissue O2 and CO2 stores and that much of these shifts can be explained by primary circulatory events. The changes in turnover rate for tissue O2 and CO2 stores could not be explained by the cardiac index changes alone but were compatible with peripheralization of venous blood volume and preferential peripheral vasoconstriction induced by apnea with elevated intrathoracic pressure during SBH. The transient compression during BHD reversed these central and peripheral circulatory changes by counteracting the increase in intrathoracic pressure. PMID- 8002499 TI - Hyperthermia stimulates nitric oxide formation: electron paramagnetic resonance detection of .NO-heme in blood. AB - Previous experiments from our laboratory have demonstrated that severe hyperthermia results in a selective loss of splanchnic vasoconstriction. Using electron paramagnetic resonance spectroscopy to scan whole blood samples collected in vivo from the portal vein and femoral artery of conscious unrestrained rats, we observed an increase in the concentration of spectroscopy detectable species in portal venous blood of all heat-stressed animals. These spectra consisted of at least three distinct species: one with a broad feature having an effective g factor for the unpaired electron (g) of 2.06 assigned to the copper-binding acute phase protein ceruloplasmin, and two with narrower features that evolved at core temperatures > 39 degrees C representing a semiquinone radical and .NO-heme. This heat-induced signal displays the classic nitrogen triplet hyperfine structure (nitrogen hyperfine splitting constant = 17.5 gauss, centered at g = 2.012) that is consistent with a five-coordinate heme complex and is characteristic of an unpaired electron coupled to nitrogen in the ferrous .NO-heme adduct [(alpha 2+NO) beta 3+]2. The intensity of this signal increased approximately twofold as core temperature rose to > 39 degrees C, peaking 1 h post-heat exposure at greater than threefold basal concentration. This species was not seen in corresponding arterial blood samples. This is the first demonstration that whole body hyperthermia produces increased concentrations of radicals and metal binding proteins in the venous blood of the rat and suggests that severe hyperthermia stimulates an enhanced local release of .NO within the splanchnic circulation. PMID- 8002500 TI - Serial distribution of airway mechanical properties in dogs: effects of histamine. AB - We measured respiratory input impedance (Zin; 8-2,048 Hz) in five dogs (anesthetized, tracheostomized, vagotomized, and mechanically ventilated) during 80 s of apnea after a bolus intravenous injection of saline or histamine (5.0 mg). In the control case, three antiresonances in Zin were found in four of the dogs, whereas in the remaining dog only two were found. The magnitude and frequency of these antiresonances were significantly altered after bronchoconstriction. To interpret Zin, a model incorporating detailed airway geometry, asymmetrical branching, and nonrigid airway walls was developed. The model fit both the saline and histamine Zin data well and predicted a serial distribution of bronchoconstriction consistent with known effects of histamine; i.e., the diameters of the most peripheral airways were reduced (26% of their control values), whereas tracheal diameters were not significantly affected. The model provided estimates of tracheal diameters that were well correlated (r = 0.92) with direct measurements. Control estimates of soft tissue viscosity (1.63 +/- 0.42 cmH2O.s) and Young's modulus (406 +/- 125 cmH2O) compared closely with values in the literature. These results indicate that bronchoconstriction induced by histamine results in significant changes in Zin over this frequency range and that by using this data analysis approach definitive physiological parameters relative to airway geometry and wall mechanical properties can be obtained from measurements made at the airway opening. PMID- 8002501 TI - Regional lung hematocrit variation and assessment of acute lung injury. AB - Estimating blood content in the lung remains a key step in calculating lung water volume and microvascular permeability. We studied the effect of regional lung hematocrit (Hct) variation on assessment of acute lung injury. Escherichia coli endotoxin was administered in guinea pigs intravenously. Lung injury was evaluated by measuring the wet-to-dry weight ratio (W/D) and transvascular 125I labeled albumin leakage for 3 h [tissue-to-plasma 125I-albumin ratio (T/P)] in five tissue samples from each animal. Residual blood content was corrected using either 51Cr-red blood cells as a blood cell marker, 99mTc-albumin as a plasma marker, or both, injected 10 min before the guinea pigs were killed. Lung Hct, estimated from the marker counts of lung and peripheral blood samples, was lower than peripheral blood Hct; intraindividual variation, represented by the standard deviation in each subject, was 0.024 +/- 0.015 for the control group (coefficient of variation 8.0 +/- 5.1%) and 0.026 +/- 0.013 for the endotoxin group (coefficient of variation 8.5 +/- 4.1%). Uncorrected W/D for residual blood content was greater than the corrected W/D. 99mTc-albumin correction gave values closer to the W/D corrected by both markers. T/P corrected by 99mTc-albumin showed smaller data variations than the values obtained with 51Cr-red blood cell correction, which was affected by variations in lung Hct. We recommend using a plasma marker to correct for blood content in assessing acute lung injury by W/D and T/P. PMID- 8002502 TI - Longitudinal distribution of ozone absorption in the lung: effects of respiratory flow. AB - In our previous work, we developed a bolus inhalation apparatus and measured the longitudinal distribution of ozone (O3) uptake in intact human lungs at a quiet respiratory flow of 250 ml/min. The objective of the present study was to determine the effect of alternative respiratory flows between 150 and 1,000 ml/s. Uptake was expressed as the O3 absorbed during a single breath relative to the amount of O3 in the inhaled bolus (lambda). Measurements of lambda were correlated with the penetration volume of the bolus into the respiratory tract (Vp). Vp in the range of 20-70 ml was considered to indicate upper airways (UA), the Vp interval of 70-180 ml was identified as lower conducting airways (CA), and Vp > 180 ml was associated with the respiratory air spaces (RA). During quiet oral breathing at 250 ml/s, lambda increased smoothly as Vp increased, with 50% of the inhaled O3 absorbed in the UAs and the remainder absorbed within the CAs such that no O3 reached the RAs. The effect of increasing the respiratory flow was to shift the lambda-Vp distribution distally such that significantly less O3 was absorbed in the UAs and CAs and some O3 reached the RAs. For example, at 1,000 ml/s, only 10% of the inhaled O3 was absorbed in UAs and 65% was absorbed in the CAs such that 25% reached the RAs.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8002503 TI - Interleukin-2 therapy reverses some immunosuppressive effects of skeletal unloading. AB - Using antiorthostatic suspension, we characterized hematopoietic changes that may be responsible for the detrimental effect of skeletal unloading on macrophage development. Skeletally unloaded mice had suppressed macrophage development in unloaded and loaded bones, which indicated a systemic effect. Bone marrow cells from unloaded mice secreted less macrophage colony-stimulating factor and interleukin-6 than control mice. Additionally, T-lymphocyte proliferation was reduced after skeletal unloading. We show that polyethylene glycol-interleukin-2 therapy reversed the effects of skeletal unloading on macrophage development and cell proliferation. PMID- 8002504 TI - Role of nitric oxide and prostaglandins in the regulation of diaphragmatic arteriolar tone in the rat. AB - We evaluated by intravital microscopy in rats the relative importance of nitric oxide (NO) and prostaglandins in 1) the maintenance of basal diaphragmatic arteriolar tone and 2) the response of diaphragmatic arterioles to the endothelium-dependent vasodilator acetylcholine (ACh). One hundred two mechanically ventilated rats were studied. Separate applications of N omega-nitro L-arginine (L-NNA) and mefenamic acid (MA), which are specific inhibitors of NO and prostaglandin synthesis, respectively, elicited a significant reduction in basal diaphragmatic arteriolar diameter. A dramatic potentiation of the effect of each inhibitor was observed when both agents were applied simultaneously. ACh application induced a significant and dose-dependent increase in arteriolar diameter that was not significantly modified by the separate application of L-NNA or MA. Conversely, the simultaneous administration of L-NNA and MA almost completely prevented ACh-induced arteriolar dilatation. Dilatation in response to sodium nitroprusside was not significantly modified in the presence of both inhibitors. These results suggest that NO and prostaglandins act in concert to regulate basal diaphragmatic arteriolar tone and to mediate diaphragmatic arteriolar response to ACh. PMID- 8002505 TI - Surface activity of rabbit pulmonary surfactant subfractions at different concentrations in a captive bubble. AB - This study investigates the surface activity of rabbit pulmonary surfactant subfractions at different concentrations in a new pressure-driven captive bubble surfactometer, which provides more rigorous testing conditions than heretofore applied to this material. Subfractions were separated by centrifugation of lavage return into a third (P3; 1,000 x average g, 20 min), a fourth (P4; 60,000 x average g, 60 min), and a fifth (P5; 100,000 x average g, 16 h) pellet. At 2.0 mg phospholipid/ml, P3 and P4 demonstrated more rapid adsorption, lower minimum surface tensions on first and subsequent compressions, and lower monolayer compressibilities than did P5. This surface activity of P3 and P4 increased with concentration between 0.1 and 2.0 mg phospholipid/ml. Adsorption rate constants were approximately 10,000 times faster than desorption constants. We conclude that, in a normal lung, components of P3 and P4 determine alveolar surface tension. We speculate that under special circumstances even the less surface active P5 could have an important influence at the air-water interface. PMID- 8002506 TI - Gender-related differences in the baroreceptor reflex control of heart rate in normotensive humans. AB - The present study investigates the baroreceptor reflex control of heart rate (HR) of normotensive male and female human volunteers under two conditions: bolus- and infusion-evoked elevations of blood pressure by intravenous administration of phenylephrine. Average age and blood pressure were similar in both sexes, but females had a significantly lower heart period (HP; higher HR). A major difference existed between the two sexes when the blood pressure was elevated by the bolus method. Females had a significantly (50%) smaller baroreflex sensitivity (regression coefficient), which inferred a gender-related difference in baroreceptor reflex control of HR. However, because a positive correlation existed between basal HP and baroreflex sensitivity, it was important to investigate whether this difference was related to the significantly lower basal HP in females. This possibility was ruled out because a similar difference still existed when the data were collected from another group of females who had basal HP values similar to those of males. This gender-related difference in baroreceptor reflex control of HR seems to depend on the pattern by which the pressor stimulus is evoked. The baroreceptor HP response to a slowly developing pressor response that was maintained at a steady-state level was very similar in both sexes. Because the HP response to abrupt (bolus-evoked) pressor stimuli mainly reflects the activity of the vagal component, our findings suggest that the cardiac vagal component seems to play a substantially smaller role in the baroreflex-mediated bradycardia in females. PMID- 8002508 TI - Simulation of cardiovascular response to lower body negative pressure from 0 to 40 mmHg. AB - This paper presents a mathematical model for simulation of the human cardiovascular response to lower body negative pressure (LBNP) up to -40 mmHg both under normal conditions and when arterial baroreflex sensitivity or leg blood capacity (LBC) is altered. Development of the model assumes that the LBNP response could be explained solely on the bases of 1) blood volume redistribution, 2) left ventricular end-diastolic filling, 3) interaction between left ventricle and peripheral circulation, and 4) modulations of peripheral resistances and heart rate by arterial and cardiopulmonary baroreflexes. The model reproduced well experimental data obtained both under normal conditions and during complete autonomic blockade; thus it is validated for simulation of the cardiovascular response from 0 to -40 mmHg LBNP. We tested the ability of the model to simulate the changes in LBNP response due to a reduction in LBC. To assess these changes experimentally, six healthy men were subjected to LBNP of 15, -30, and -38 mmHg with and without wearing elastic compression stockings. Stockings significantly reduced LBC (from 3.9 +/- 0.3 to 1.8 +/- 0.4 ml/100 ml tissue at -38 mmHg LBNP; P < 0.01) and attenuated the change in heart rate (from 23 +/- 4 to 8 +/- 3% at -38 mmHg LBNP; P < 0.05). The model accurately reproduced this result. The model is useful for assessing the influence of LBC or other parameters such as arterial baroreflex sensitivity in diminishing the orthostatic tolerance of humans after spaceflight, bed rest, or endurance training. PMID- 8002507 TI - Effects of strength training on total and regional body composition in older men. AB - The effects of a 16-wk strength-training program on total and regional body composition were assessed by dual-energy X-ray absorptiometry (DEXA), magnetic resonance imaging (MRI), and hydrodensitometry in 13 untrained healthy men [60 +/ 4 (SD) yr]. Nine additional men (62 +/- 6 yr) served as inactive controls. The strength-training program resulted in substantial increases in both upper (39 +/- 8%; P < 0.001) and lower (42 +/- 14%; P < 0.001) body strength. Total fat-free mass (FFM) increased by 2 kg (62.0 +/- 7.1 to 64.0 +/- 7.2 kg; P < 0.001), and total fat mass decreased by the same amount (23.8 +/- 6.7 to 21.8 +/- 6.0 kg; P < 0.001) when measured by DEXA. When measured by hydrodensitometry, similar increases in FFM (61.3 +/- 7.8 to 63.0 +/- 7.6 kg; P < 0.01) and decreases in fat mass (23.8 +/- 7.9 to 22.1 +/- 7.7 kg; P < 0.001) were observed. When measured by DEXA, FFM was increased in the arms (6.045 +/- 0.860 to 6.418 +/- 0.803 kg; P < 0.01), legs (19.416 +/- 2.228 to 20.131 +/- 2.303 kg; P < 0.001), and trunk (29.229 +/- 4.108 to 30.134 +/- 4.184 kg; P < 0.01), whereas fat mass was reduced in the arms (2.383 +/- 0.830 to 2.128 +/- 0.714 kg; P < 0.01), legs (7.583 +/- 1.675 to 6.945 +/- 1.551 kg; P < 0.001), and trunk (12.216 +/- 4.143 to 11.281 +/ 3.653 kg; P < 0.01) as a result of training.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8002509 TI - Effect of glucose infusion on endurance performance after beta-adrenoceptor blocker administration. AB - To investigate the effect of glucose (Glc) infusion on endurance performance after beta-adrenoceptor blockade, eight healthy male volunteers performed four endurance cycle ergometer tests at 67% of maximal work load after 80 mg of propranolol (Pr) or placebo (Pl) were administered orally in combination with a continuous infusion of Glc (0.5 g/min) or saline (Sal). The order of the tests was randomized. Endurance times were 53 +/- 6 (SE), 64 +/- 7, 26 +/- 5, and 31 +/ 6 min after Pl+Sal, Pl+Glc, Pr+Sal, and Pr+Glc, respectively (P < 0.001). Glc infusion increased endurance after Pl (P < 0.05) but not after Pr. Glc infusion resulted in significantly higher plasma Glc concentrations during exercise compared with Sal infusion (P < 0.001). Glc infusion had no effect on cardiorespiratory or other metabolic variables. Plasma ammonia concentration was increased during the Pr tests (P < 0.001) but reached similar values at exhaustion in all tests and was not affected by Glc infusion. The maintenance of plasma Glc concentration during endurance exercise at or above preexercise levels did not improve the reduction of endurance performance after Pr, indicating that the availability of blood Glc is not a limiting factor in this process. PMID- 8002510 TI - Contribution of body composition and physical activity to age-related decline in peak VO2 in men and women. AB - We examined the contribution of variations in body composition and leisure time physical activity to the age-related decline in peak oxygen consumption (VO2) in men and women. Healthy males 17-80 yr old (n = 378) and females 18-81 yr old (n = 224) were characterized for peak VO2 from a treadmill test to exhaustion, fat free mass and fat mass by underwater weighing, and leisure time physical activity. Peak VO2 showed a greater absolute decline (P < 0.05) with age in males (r = -0.70, slope = -0.034 l.min-1.yr-1; P < 0.01) than in females (r = -0.78, slope = -0.028 l.min-1.yr-1; P < 0.01). After statistically controlling for differences in fat-free mass and fat mass, the decline in peak VO2 was diminished in both sexes, although a greater rate of decline persisted in males (r = -0.47, slope = -0.016 l.min-1.yr-1; P < 0.01) than in females (r = -0.39, slope = -0.009 l.min-1.yr-1; P < 0.01). We found that the addition of leisure time physical activity (independent of body composition) to the regression model further attenuated the rate of decline in males (r = -0.40, slope = -0.013 l.min-1.yr-1; P < 0.01) but did not alter the age-related decline in peak VO2 in females (r = 0.39, slope = -0.009 l.min-1.yr-1; P < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8002512 TI - Impact of parallel heterogeneity on a continuum model of the pulmonary arterial tree. AB - Model arterial trees were constructed following rules consistent with morphometric data, Nj = (Dj/Da)-beta 1 and Lj = La(Dj/Da)beta 2, where Nj, Dj, and Lj are number, diameter, and length, respectively, of vessels in the jth level; Da and La are diameter and length, respectively, of the inlet artery, and beta 1 and beta 2 are power law slopes relating vessel number and length, respectively, to vessel diameter. Simulated heterogeneous trees approximating these rules were constructed by assigning vessel diameters Dm = Da[2/(m + 1)]1/beta 1, such that m-1 vessels were larger than Dm (vessel length proportional to diameter). Vessels were connected, forming random bifurcating trees. Longitudinal intravascular pressure [P(Qcum)] with respect to cumulative vascular volume [Qcum] was computed for Poiseuille flow. Strahler-ordered tree morphometry yielded estimates of La, Da, beta 1, beta 2, and mean number ratio (B); B is defined by Nk + 1 = Bk, where k is total number of Strahler orders minus Strahler order number. The parameters were used in P(Qcum) = Pa [formula: see text] and the resulting P(Qcum) relationship was compared with that of the simulated tree, where Pa is total arterial pressure drop, Q is flow rate, Ra = (128 microLa)/(pi D4a (where mu is blood viscosity), and Qa (volume of inlet artery) = 1/4D2a pi La. Results indicate that the equation, originally developed for homogeneous trees (J. Appl. Physiol. 72: 2225-2237, 1992), provides a good approximation to the heterogeneous tree P(Qcum). PMID- 8002511 TI - Systemic and diaphragmatic oxygen delivery-consumption relationships during hemorrhage. AB - When tissue O2 delivery falls below a critical threshold, tissue O2 uptake (VO2) becomes limited. We compared critical O2 delivery and critical and maximum O2 extraction ratios of the resting and contracting left hemidiaphragm with those of nondiaphragmatic tissues in seven dogs. The left hemidiaphragm was perfused through the left inferior phrenic artery with blood from the left femoral artery. Phrenic venous blood was sampled through a catheter in the inferior phrenic vein. Systemic O2 delivery was reduced in stages by controlled hemorrhage. Left diaphragmatic VO2 during rest and during 3 min of continuous stimulation (3 Hz) of the left phrenic nerve and VO2 of the remaining nonleft hemidiaphragmatic tissues were measured at each stage. Critical diaphragmatic O2 delivery for the resting diaphragm averaged 0.8 +/- 0.16 ml.min-1.100 g-1 with a critical O2 extraction ratio of 65.5 +/- 6%. In the contracting diaphragm, they averaged 5.1 +/- 0.9 ml.min-1.100 g-1 and 81 +/- 5%, respectively. Whole body O2 delivery at which resting diaphragmatic VO2 became supply limited was similar to that for nondiaphragmatic tissues. By comparison, supply limitation of VO2 occurred at a higher systemic O2 delivery in the contracting diaphragm than in the rest of the body despite the increase in critical diaphragmatic extraction ratio. Thus, oxygenation of the isolated diaphragm does not appear to be preferentially preserved during generalized reductions in O2 delivery. These results suggest that, in diseases associated with increased work of breathing and decreased O2 delivery, the diaphragm may become metabolically impaired before limitation of VO2 is observed systemically. PMID- 8002513 TI - Exercise O2 transport model assuming zero cytochrome PO2 at VO2 max. AB - An analogy is drawn between cytochrome aa3 function and a polarographic cathode at which the potential of -0.6 V captures all O2 diffusing to the surface, achieving maximal O2 consumption (VO2max) by eliminating O2 backpressure and outward diffusion from the surface, defined herein as zero surface PO2. The relationship of O2 consumption (as %VO2max) to muscle venous, myoglobin, and cytochrome PO2 is modeled assuming that cytochrome aa3 PO2 reaches zero at VO2max, incorporating published data on the profile of leg venous PO2, pH, and blood lactate vs. work. Equations describe hemoglobin and myoglobin O2 dissociation and the Bohr effect of acid on O2 unloading. The O2 gradient from capillary blood to cytochrome aa3 is assumed to be proportional to O2 consumption. The model suggests that 1) to extract 75% of the O2 from myoglobin at VO2max, myoglobin must lie 90% down the O2 gradient from capillary to cytochrome; 2) the Bohr effect adds 15-30% to VO2max and keeps venous PO2 almost constant as work rises from 60 to 100% of VO2max; and 3) in steady heavy work, the rising arterial lactate may impede lactate excretion from muscle, reduce anaerobic ATP generation, and shift the energy balance toward aerobic metabolism. The zero PO2 hypothesis facilitates modeling and may be the key to understanding the physiological limitation of work. PMID- 8002514 TI - Excitatory connections between upper cervical inspiratory neurons and phrenic motoneurons in cats. AB - This study aimed to determine whether upper cervical inspiratory neurons (UCINs), which are localized in the intermediolateral part of the gray matter of the upper cervical segments, have propriospinal connections to phrenic motoneurons of the ipsilateral lower cervical segment in anesthetized cats. Unit action potentials of UCINs were extracellularly recorded simultaneously with ipsilateral phrenic nerve activity. To eliminate the descending influences from medullary respiratory neurons to phrenic motoneurons, bulbospinal conduction paths were temporarily blocked by focal cooling applied to the ventral caudal medulla at the pyramidal decussation level by means of a cooling thermode (1 mm tip diam). By using a spike-triggered method, during cooling phrenic nerve activities were evoked by UCIN spikes that were elicited by microinjection of L-glutamate for 20 of the 55 (36%) UCIN units examined. The onset latencies of these phrenic motoneuron responses ranged from 1.5 to 7.1 ms (mean 3.6 ms), depending on synaptic transmission delays. These results clearly demonstrate that UCINs have, at least in part, excitatory mono- and paucisynaptic connections with ipsilateral phrenic motoneurons. PMID- 8002515 TI - Higher exercise performance and lower VO2max in Tibetan than Han residents at 4,700 m altitude. AB - To examine the hypothesis that the pathway of adaptation to high altitude in natives differs considerably from that in newcomers, we measured maximal O2 uptake (VO2max), minute ventilation, anaerobic threshold (AT), blood lactate, and blood gases during maximal exercise in 17 lifelong Tibetan residents and 14 acclimatized Han Chinese newcomers living at the altitude of 4,700 m. The two groups were similar in age, height, and weight, and the subjects were nonathletes. Although VO2max was significantly lower in the Tibetans than in the Hans (30.4 +/- 1.5 vs. 36.0 +/- 1.9 ml.min-1.kg-1 STPD; P < 0.05), at maximal exercise effort the exercise workload was greater (167.7 +/- 4.2 vs. 150.0 +/- 5.9 W; P < 0.05). The mean AT values (in % VO2max) in the Tibetan and Han subjects were 84.1 and 61.6%, respectively (P < 0.01). Minute ventilation at maximal exercise was significantly lower in the Tibetans than in the Hans (68.4 +/- 3.4 vs. 79.7 +/- 4.1 l/min BTPS; P < 0.05), whereas heart rate at maximal effort was equivalent in the two groups. The Tibetans showed lower blood lactate value than did the Hans both before and at the end of exercise. We conclude that the Tibetan natives have higher exercise performance and AT but lower VO2max and blood lactate concentration than do acclimatized Han newcomers. These results may reflect the effects of genetic or peripheral adaptation factors in the Tibetan natives. PMID- 8002516 TI - Impaired thermoregulatory cutaneous vasodilation in spontaneously hypertensive rats. AB - Spontaneously hypertensive rats (SHR) are more suitable to heat stroke than are normotensive controls. To determine whether hypertension impairs thermoregulatory reflex cutaneous vasodilation we observed the tail skin vasodilator responses to body heating in male SHR and normotensive Wistar-Kyoto rats (WKY) anesthetized with chloralose and urethan (80 mg/kg and 500 mg/kg ip, respectively). A pulsed Doppler flow probe was placed on the caudal artery at its origin to monitor tail blood flow (TBF) velocity (the tail skin is the major thermoregulatory organ of the rat), and a catheter was placed in a femoral artery to monitor arterial pressure and heart rate. Internal temperature was measured via a thermistor placed approximately 10 cm down the esophagus into the gastrointestinal tract. During normothermia, TBF was not different between SHR and WKY (0.10 +/- 0.01 vs. 0.15 +/- 0.02 kHz; P > 0.05), whereas tail vascular conductance (TVC) was significantly lower in SHR vs. WKY (0.73 +/- 0.14 vs. 1.88 +/- 0.31 Hz/mmHg; P < 0.05). In response to body heating (tail remained exposed to room temperature), the increases in TBF and TVC were markedly less SHR than in WKY (0.73 +/- 0.14 kHz and 6.03 +/- 1.11 Hz/mmHg vs. 2.61 +/- 0.35 kHz and 22.48 +/- 2.69 Hz/mmHg, respectively). After lumbar sympathectomy, TBF and TVC were not different from the values observed during hyperthermia in both groups. This indicates that the impaired cutaneous vasodilation observed in SHR was not due to failure to withdraw sympathetic vasoconstrictor tone. We conclude that thermoregulatory reflex vasodilation of the cutaneous vasculature is markedly impaired in SHR. PMID- 8002518 TI - Vascular impedance analysis in dog lung with detailed morphometric and elasticity data. AB - On the basis of experimentally measured morphometric and elasticity data and model-derived mean pressure-flow conditions, we attempt a theoretical modeling of pulsatile flow in the whole lung. In the model we use the "elastic tube" for arteries and veins, and the vascular impedance in arteries and veins follows Womersley's theory and electric analogue. We employ the "sheet-flow" theory to describe the flow in the capillaries and to obtain the microvascular impedance matrix. The characteristic impedance of each order along the vascular tree, the input impedance at the capillary entrance and exit, and the pulmonary arterial input impedance at the main pulmonary artery are computed under certain physiological conditions. Using the pulsatile flow model, we investigate the effects of arterial vascular obstruction on pulmonary vascular impedance. The model-derived data are compared with the available experimental results in the literature. PMID- 8002517 TI - Roles of intra- and extracellular carbonic anhydrase in alveolar-capillary CO2 equilibration. AB - Alveolar-capillary CO2 equilibration involves diffusive equilibration of CO2 across the blood-gas barrier and chemical equilibration of perfusate CO2-HCO-3-H+ reactions. These processes are governed by different, but related, driving forces and conductances. The present study examined the importance of pulmonary carbonic anhydrase (CA) for diffusive and reactive CO2 equilibration in isolated rat lungs. Lungs were perfused with salines containing membrane-impermeant or permeant inhibitors of CA. Measurements of CO2 excretion rate, equilibrated venous and arterial PCO2 and pH, and postcapillary pH and PCO2 disequilibria were used, together with our previous model of CO2-HCO-3-H+ reactions and transport in saline-perfused capillaries (Bidani et al. J. Appl. Physiol. 55: 75-83, 1983), to compute the relevant driving forces and conductances. Reactive CO2 equilibration was markedly affected by extracellular (vascular) CA activity but not by the activity of intracellular (cytosolic) CA. The driving force for CO2 diffusion was strongly influenced by vascular CA activity. The conductance for CO2 diffusion was independent of CA activity. The minimum conductance for CO2 diffusion was estimated to be 700-800 ml.min-1.Torr-1. The results indicate that extracellular vascular CA activity influences both diffusive and reactive CO2 equilibration. However, cytosolic CA has no detectable role in alveolar-capillary CO2 equilibration. PMID- 8002519 TI - Diameters of juxtacapillary venules determined by oil-drop method in rat lung. AB - We report a new method for precise quantification of lung microvascular diameter. Isolated blood-perfused rat lungs (500-g Sprague-Dawley rats) at constant inflation pressure [alveolar pressure (PA)] and stopped blood flow were viewed by microscopy and video. Subpleural venules of the second and third postcapillary generations were microinjected with oil colored with Sudan Black. Vascular pressure (Pvas) was varied in steps, and at each step the horizontal diameter (DH) and the length of the oil-filled segment were determined by microcaliper measurements of the replayed video image. At PA = 5 cmH2O, a decrease in Pvas from 25 to 0 cmH2O decreased DH in the second-generation venules from 55 +/- 2 (SE) to 41 +/- 1 microns (n = 13) and in the third-generation venules from 96 +/- 6 to 73 +/- 6 microns (n = 6). The constant-volume oil-filled segment conformed to the cylinder formula in that decreases in DH correlated linearly with 1/ square root of length, thereby indicating that at all Pvas values venular geometry was constant and probably circular in cross section. The decrease in Pvas to -5 cmH2O did not further decrease DH. At Pvas = 10-25 cmH2O, an increase in PA to 15 cmH2O did not significantly increase DH, although the increase in PA did diminish the slope (compliance) of the DH-Pvas relationship in second- but not third-generation venules. We conclude that 1) lung expansion decreases compliance of juxtacapillary venules, 2) venules retain circular cross sections at Pvas between -5 and 25 cmH2O, and 3) venules are patent at subzero Pvas. PMID- 8002520 TI - Hypoxia similarly impairs metabolic responses to cutaneous and core cold stimuli in conscious rats. AB - Cold exposure elicits several thermoregulatory responses, including an increased metabolic heat production from shivering and nonshivering thermogenesis. The increased metabolism can be in response to body core and/or body cutaneous cooling. Hypoxic hypoxia has been shown to attenuate the metabolic response to cutaneous cooling. We measured metabolic heat production in adult conscious rats during independent cutaneous and core cooling, during normoxia and hypoxia, to 1) test the hypothesis that hypoxia suppresses the metabolic response to independent core cooling and 2) determine whether hypoxia acts preferentially on the response to cutaneous or core cooling. The animals were studied in a temperature controlled metabolic chamber, and body core temperature was controlled by an abdominal heat exchange coil. Ambient temperature was varied (10, 19, and 28 degrees C) while core temperature was clamped at 37 degrees C or core temperature was varied (33, 35, and 37 degrees C) at a stable ambient temperature of 28 degrees C. Our data indicate that although the sensitivity of the metabolic response to core cooling is about five to six times that to cutaneous cooling. Hypoxia similarly attenuates thermoregulatory responses to both stimuli. PMID- 8002521 TI - Bronchial and reverse pulmonary venous blood flow protect the lung from ischemia reperfusion injury. AB - We used an intact in vivo canine model of pulmonary ischemia-reperfusion injury to evaluate whether the bronchial circulation or reverse pulmonary venous blood flow would protect the lung from injury during 2 h of unilateral pulmonary arterial (PA) occlusion and lung deflation. Serial measurements of regional extravascular density and transcapillary protein flux were made after reperfusion by using the quantitative imaging technique of positron emission tomography. Twenty-one animals were divided into four experimental groups. In all experimental groups, the left PA was clamped and the left lung was allowed to collapse and remain unventilated for a period of 2 h. In addition, in group I (n = 5) the left bronchial circulation was disrupted and the left pulmonary veins were clamped, in group II (n = 5) the bronchial circulation and the pulmonary veins were left intact, in group III (n = 6) the bronchial circulation was left intact but the pulmonary veins were clamped, and in group IV (n = 5) the bronchial circulation was disrupted but the pulmonary veins remained patent. The rate of protein flux in the left lung was increased only in group I (complete ischemia with lung deflation) [mean 195 x 10(-4) min-1 (range 85-453 x 10(-4) min 1) at 0.25 h and 114 x 10(-4) min-1 (range 22-200 x 10(-4) min-1) at 3 h] after reventilation and PA reperfusion (normal = 49 +/- 31 x 10(-4) min-1). Extravascular density increased significantly from 0.25 to 3 h only in group I.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8002522 TI - Influence of exercise training on myocardial beta-adrenergic signal transduction: differential regulation with age. AB - Exercise training is known to increase cardiovascular performance and decrease heart rate. Because activation of adenylyl cyclase is an important factor in beta adrenergic signal transduction and in the decline in signal transduction with age, we hypothesized that some of the effects of exercise training may be mediated by changes in postreceptor activation of adenylyl cyclase. To this end, we assessed isoproterenol-, G protein-, and forskolin-mediated activation of adenylyl cyclase as well as G protein immunoreactivity in the myocardium from young and senescent F-344 rats with and without prior exercise training by treadmill running. Isoproterenol, beta-gamma-imidoguanosine 5'-triphosphate, and forskolin stimulation of adenylyl cyclase activity declined by approximately 50% with age. Training increased the stimulation in the senescent rats and decreased the stimulation in the young rats such that the age-related decline in signal transduction was no longer significant. Gs alpha protein immunoreactivity was unchanged by age or training. These data suggest that in young rats exercise training decreases beta-adrenergic signal transduction, whereas in older rats training increases signal transduction, partially offsetting the decline in signal transduction with age. PMID- 8002524 TI - Magnesium attenuates pulmonary hypertension due to hypoxia and group B streptococci. AB - We investigated whether hypermagnesemia alleviates hypoxic or group B streptococcal (GBS) pulmonary hypertension (PH). Hypoxic PH was induced and maintained in 14 lambs by continuous ventilation with 12% oxygen. GBS PH was induced and maintained in 16 lambs by the continuous infusion of 5-10 x 10(8) colony-forming units.kg-1.h-1 of GBS. After the onset of PH, lambs were randomized to receive either magnesium sulfate (MgSO4, intermittent boluses of 0.38 mmol/kg, with a continuous infusion of 0.15 mmol.kg-1.h-1) or a similar volume of normal saline. Hypermagnesemia lowered pulmonary arterial pressure (PAP) and delayed the fall in systemic arterial pressure and stroke volume index seen in the control animals (each P < 0.05). At a serum magnesium concentration ([Mg]) of 2.75 +/- 0.25 mmol/l, PAP was 27 +/- 3 compared with 40 +/- 4 Torr in the control animals ([Mg] = 0.87 +/- 0.06 mmol/l; P < 0.05). In the GBS PH trial, hypermagnesemia prevented the continued increase in PAP seen in the control animals. At [Mg] = 2.15 +/- 0.07 mmol/l, PAP fell 2 +/- 1 Torr from prerandomization values, whereas it rose 4 +/- 2 Torr in the control animals ([Mg] = 0.59 +/- 0.07 mmol/l; P < 0.05). However, during the same time the systemic arterial pressure fell further in the magnesium-treated animals (-19 +/- 1 vs. -2 +/- 5 Torr). MgSO4 attenuates PH in both models but may cause systemic hypotension in sepsis. PMID- 8002523 TI - Modulation of respiratory rhythm by alpha 2-adrenoceptors in awake and anesthetized goats. AB - The purpose of this study was to examine the effects of alpha 2-adrenoceptor agonists in the control of breathing with goats that were either awake (n = 7) or anesthetized and artificially ventilated (n = 11). Awake goats infused intravenously with either of the alpha 2-agonists clonidine (1.0-6.0 micrograms/kg) or guanabenz (15.0-63.0 micrograms/kg) exhibited two distinct ventilatory patterns. One pattern was characterized by tachypnea in which respiratory frequency and minute ventilation increased to approximately 50% above control values. A second ventilatory pattern consisted of slow breathing with reductions of respiratory frequency and minute ventilation and highly variable expiratory duration intervals. These two patterns were unaffected by bilateral carotid body denervation. In anesthetized goats, alpha 2-agonists also caused an arrhythmia in phrenic nerve activity that was similar to the slow breathing pattern seen in awake goats. Respiratory disturbances were abolished by the selective alpha 2-receptor antagonist SKF-86466 (100-500 micrograms/kg), indicating that the effects are mediated by alpha 2-receptors. The results suggest that stimulation of alpha 2-adrenoceptors generally has an inhibitory effect on breathing in goats. The disruption of ventilation with clonidine or guanabenz suggests that alpha 2-adrenoceptors may play an important role in the control of central respiratory rhythm. PMID- 8002525 TI - Interaction of transferrin saturated with iron with lung surfactant in respiratory failure. AB - Proteins that decrease the surface activity of surfactant accumulate in epithelial lining fluid in respiratory failure. The aim of this study was to isolate a surfactant inhibitor from the airways of rabbits in acute respiratory failure induced by bronchoalveolar lavage (BAL). This inhibitor was identified as being transferrin (TF). Unlike serum TF, TF recovered in respiratory failure was saturated with iron (Fe(3+)-TF). Fe(3+)-TF decreased the surface activity of normal surfactant in vitro, whereas iron-free TF had no effect. In the presence of H2O2 and a reducing agent, Fe(+3)-TF inactivated the surfactant complex: the surface absorption rate was decreased, immunoreactive surfactant protein A was decreased, and malondialdehyde was formed. The acute effects of Fe(3+)-TF and iron-free TF applied to the airways were studied in animal models. In respiratory failure induced by BAL, Fe(3+)-TF deteriorated respiratory failure, whereas iron free TF had no effect. In respiratory failure induced by hyperoxia for 48 h, administration of iron-free TF ameliorated the respiratory failure and improved the surface activity in BAL. We propose that Fe(3+)-TF accumulating in epithelial lining fluid during lung damage contributes to surfactant inhibition and promotes the formation of free radicals that inactivate the surfactant system. PMID- 8002526 TI - Effect of hyperoxia at 1 and 2 ATA on hypoxia and hypercapnia in human skin during experimental inflammation. AB - Transcutaneous PO2 and PCO2 measurements and estimates of skin respiration were monitored at different levels of inspired PO2 in 20 healthy adults during the first 4 days of the tuberculin reaction, a convenient model of acute inflammation. Hyperoxia at 1 and 2 ATA significantly increased transcutaneous PO2 levels in undisturbed and in inflamed skin but did not fully correct the relative hypoxia at the site of inflammation. Hypercapnia was reduced with O2 breathing at 2 ATA. The apparent rate of O2 consumption at the reaction site was raised during hyperoxia, most prominently at 2 ATA. The most intense reactions showed a central relative slowing of laser-Doppler blood flow indicative of microcirculatory impairment. The extent of the relative hypoxia and hypercapnia was greatest in these strongest reactions. The density of lymphocytes and monocytes in biopsies of 48-h reactions was loosely related to the corresponding transcutaneous PO2 measurements. The present study provides evidence that diffusion barriers, in addition to increased local respiration, can contribute to the apparent hypoxia and hypercapnia of this inflammatory model. PMID- 8002527 TI - Reversal of pulmonary capillary ischemia-reperfusion injury by rolipram, a cAMP phosphodiesterase inhibitor. AB - Isoproterenol (ISO) and forskolin, agents that increase adenosine 3',5'-cyclic monophosphate (cAMP) via adenylyl cyclase activation, reverse lung injury associated with increased microvascular permeability. We studied the role of rolipram, a relatively isozyme-selective cAMP phosphodiesterase (PDE) inhibitor, in reversing increased capillary permeability due to ischemia-reperfusion (I/R), a form of oxidant injury in the lung, by using the isolated perfused rat lung model. Rolipram (2 microM) administered after 45 min of ischemia and 45 min of reperfusion reduced I/R-increased permeability as measured by the capillary filtration coefficient to control lung values. Computer image analysis of air space edema and perivascular cuffing, as well as wet-to-dry weight ratios, confirms the permeability reversal by rolipram administration. Rolipram inhibition of cAMP PDE in the lung was assessed by using [3H]adenine prelabeling adapted for the whole lung and perfusate [3H]cAMP accumulation. Rolipram failed to increase perfusate cAMP alone but dramatically increased perfusate cAMP above ISO alone. Dose-response relationships of ISO or rolipram show a close correlation of the half-maximal effective dose (ED50) for injury reversal and perfusate cAMP production. The combination of rolipram and ISO produced synergistic reversal of I/R injury. We conclude that reversal of I/R-induced increased microvascular permeability can be achieved with rolipram and that the mechanism of action of rolipram is probably through PDE isozyme-selective inhibition. The similarity of the ED50 values for cAMP efflux and reversal of permeability increases also supports a close coupling between cAMP accumulation and endothelial cell permeability. PMID- 8002528 TI - Lung vascular protein permeability in preterm fetal and mature newborn sheep. AB - The purpose of this study was to see whether there are developmental differences in the protein permeability of the pulmonary circulation that might contribute to the abnormal lung fluid balance seen in premature lambs with respiratory failure. In one series of experiments, we measured albumin turnover time, which reflects the escape rate of radiolabeled albumin from the pulmonary circulation, of five preterm fetal lambs (125 +/- 1 days gestation) and five newborn lambs (19 +/- 9 days old). Turnover time was not significantly different in fetuses (160 +/- 38 min) and newborns (141 +/- 54 min), implying a similar protein permeability of the pulmonary circulation. In additional experiments, we measured pulmonary hemodynamic and lung lymph flow responses to intravenous saline infusion in seven preterm fetal lambs (130 +/- 3 days gestation) and seven newborn lambs (14 +/- 3 days old). During saline infusion, calculated fluid filtration pressure increased by a similar amount in fetuses and newborns (3.4 +/- 0.8 and 2.8 +/- 0.9 Torr, respectively), resulting in a similar change in lung lymph flow in fetuses and newborns (0.59 +/- 0.27 and 0.55 +/- 0.25 ml.h-1.kg body wt-1, respectively). The results of these studies indicate that protein permeability of the pulmonary circulation does not change significantly during late fetal and early postnatal development. PMID- 8002529 TI - Lung volume specificity of inspiratory muscle training. AB - We examined the extent to which training-related increases of inspiratory muscle (IM) strength are limited to the lung volume (VL) at which the training occurs. IM strength training consisted of performing repeated static maximum inspiratory maneuvers. Three groups of normal volunteers performed these maneuvers at one of three lung volumes: residual volume (RV), relaxation volume (Vrel), or Vrel plus one-half of inspiratory capacity (Vrel + 1/2IC). A control group did not train. We constructed maximal inspiratory pressure-VL curves before and after a 6-wk training period. For each group, we found that the greatest improvements in strength occurred at the volume at which the subjects trained and were significantly greater for those who trained at low (36% for RV and 26% for Vrel) than at high volumes (13% for Vrel + 1/2IC). Smaller increments in strength were noted at volumes adjacent to the training volume. The range of vital capacity (VC) over which strength was increased was greater for those who trained at low (70% of VC) than at high VL (20% of VC). We conclude that the greatest improvements in IM strength are specific to the VL at which training occurs. However, the increase in strength, as well as the range of volume over which strength is increased, is greater for those who trained at the lower VL. PMID- 8002530 TI - Pressure-flow specificity of inspiratory muscle training. AB - The inspiratory muscles (IM) can be trained by having a subject breathe through inspiratory resistive loads or by use of unloaded hyperpnea. These disparate training protocols are characterized by high inspiratory pressure (force) or high inspiratory flow (velocity), respectively. We tested the hypothesis that the posttraining improvements in IM pressure or flow performance are specific to training protocols in a way that is similar to force-velocity specificity of skeletal muscle training. IM training was accomplished in 15 normal subjects by use of three protocols: high inspiratory pressure-no flow (group A, n = 5), low inspiratory pressure-high flow (group B, n = 5), and intermediate inspiratory pressure and flow (group C, n = 5). A control group (n = 4) did no training. Before and after training, we measured esophageal pressure (Pes) and inspiratory flow (VI) during single maximal inspiratory efforts against a range of external resistances including an occluded airway. Efforts originated below relaxation volume (Vrel), and peak Pes and VI were measured at Vrel. Isovolume maximal Pes VI plots were constructed to assess maximal inspiratory pressure-flow performance. Group A (pressure training) performed 30 maximal static inspiratory maneuvers at Vrel daily, group B (flow training) performed 30 sets of three maximal inspiratory maneuvers with no added external resistance daily, and group C (intermediate training) performed 30 maximal inspiratory efforts on a midrange external resistance (7 mm ID) daily. Subjects trained 5 days/wk for 6 wk. Data analysis included comparison of posttraining Pes-VI slopes among training groups.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8002531 TI - Supernormal muscle fiber conduction velocity during intermittent isometric exercise in human muscle. AB - Muscle fiber conduction velocity (MFCV) and surface electromyographic parameters were studied in the brachial biceps muscle of healthy males during voluntary intermittent isometric contractions at 50% of maximum force. Recovery in the following 15 min was then observed. The measurements were performed during duty cycles of 33, 25, and 20%. The main finding was a supernormal MFCV during the exercise phase when the duty cycle was 25 and 20%. The level continued to increase during the recovery phase. During the exercise phase when the duty cycle was 33%, the MFCV decreased slightly (suggesting that the local anaerobic threshold had been surpassed) but increased during recovery to supernormal values. The ratio of median frequency to MFCV was constant during all experiments, indicating that the changes in median frequency reflect those in MFCV. We suggest that the supernormal MFCV was due to a combination of altered membrane properties, muscle fiber swelling, and temperature increase and hypothesize that the changes of electrical properties formed part of an adaptive mechanism of the muscle fiber membrane during exercise. In that respect, the increase of the MFCV could be a component of the well-known warm-up effect. PMID- 8002532 TI - Maximum rate of force development is increased by antagonist conditioning contraction. AB - Nine subjects performed maximum contractions with the knee extensor muscles on an isokinetic device set at 4.36 rad/s. The knee extensions were preceded by isometric conditioning contractions of the antagonist knee flexor muscles. The conditioning contraction forces were 0, 25, 50, 75, and 100% of the maximum isometric force. The purpose of the study was to determine 1) the effects of graded conditioning contractions with the knee flexor muscles on the maximum performance of the quadriceps femoris and 2) whether the effects of the conditioning contractions are similarly distributed to components of the quadriceps femoris. The increased initial quadriceps femoris activation levels associated with the conditioning contractions were similarly distributed to quadriceps femoris components. In contrast with previously published research on exercise performed at substantially lower knee extension velocities, the maximum knee extension force and the work performed were not affected by the conditioning contractions. However, the maximum rate of force development increased significantly (P < 0.05). The intensity of the knee flexor conditioning contractions likely influences agonist motor unit activation variables, but this influence may be related to the speed of the agonist contraction. PMID- 8002533 TI - Detection of free radicals by electron spin resonance in rat diaphragm after resistive loading. AB - Indirect evidence supports free radical production in the diaphragm under excessive mechanical loads in both in vitro and in situ preparations. We hypothesized that free radicals are produced in the diaphragm with loads in vivo at a sufficient concentration to be detected by electron spin resonance (ESR) spectroscopy. Anesthetized rats underwent severe inspiratory resistive loading for 2.5-3 h with maintenance of blood oxygenation and arterial blood pressure by breathing 70% oxygen. The ESR spectra of four samples (freeze-clamped at liquid nitrogen temperature) from each experimental animal were compared with the spectra from a control animal breathing air and a control animal breathing 70% oxygen. We observed 1) an approximately 30% increase in intensity of free radical signal in experimental animals (n = 10) compared with control animals breathing oxygen (n = 10; P < 0.01) and control animals breathing air (n = 10; P < 0.05), 2) that oxygen alone had no effect on the ESR spectrum, and 3) the intensity of the ESR signal decreased approximately 25% in the experimental group when samples were taken 10 min postmortem, whereas no difference in signal was observed for control animals. We conclude that the diaphragm shows an increased production of free radicals associated with respiratory failure induced by resistive breathing. PMID- 8002534 TI - Effects of hyperinflation and CPAP on work of breathing and respiratory failure in dogs. AB - Increased end-expiratory lung volume (EELV) and airway resistance are both characteristic features of obstructive lung disease. Increased EELV alone loads the respiratory muscles and may cause respiratory failure, changes that could be reversed by continuous positive airway pressure (CPAP). To study the effects of elevated EELV on respiration without increased airway resistance, we used a mechanical analogue of airway closure to increase EELV in six spontaneously breathing anesthetized dogs. Hyperinflation of 0.84 +/- 0.11 liter for 30 min decreased minute ventilation from 4.8 +/- 0.37 to 3.5 +/- 0.21 l/min and increased arterial PCO2 from 40.3 +/- 1.5 to 73.2 +/- 8.1 Torr (both P < 0.01). Inspiratory work per breath increased 3-fold, work per liter increased 3.7-fold, and work per minute increased 2.8-fold (all P < 0.01). CPAP at 15 cmH2O restored minute ventilation to 4.3 +/- 0.3 l/min and reduced arterial PCO2 to 54 +/- 6.6 Torr (NS vs. baseline). All measurements of inspiratory work were also restored to baseline, but cardiac output was reduced (baseline 3.09 +/- 0.36, hyperinflation 2.71 +/- 0.36, hyperinflation + CPAP 1.94 +/- 0.29 l/min; P < 0.05, baseline vs. hyperinflation + CPAP). We conclude that increases in EELV mimic important features of airway obstruction, increase inspiratory work, and can cause respiratory failure independent of increased airway resistance. This respiratory failure is reversed by CPAP at the potential expense of hemodynamic compromise. PMID- 8002535 TI - Performance and metabolic effects of benzodiazepine during submaximal exercise. AB - The present study examined whether benzodiazepine (BZ) intake alters performance and selected hormonal and metabolic variables during submaximal exercise. Seven triathletes completed two cycling trials at 85% maximum O2 uptake starting 3 h after an ingestion of either a placebo (PLA) of gelatin or BZ (1.5 mg lorazepam) and continuing until exhaustion, according to a double-blind randomized protocol. Blood samples were collected at rest; 5, 10, and 15 min; and exhaustion for dopamine (DA), norepinephrine (NE), epinephrine (Epi), adrenocorticotropic hormone (ACTH), cortisol (CORT), insulin (INS), free fatty acid, blood glucose, and lactate (La) determinations. Time of cycling was not significantly changed after BZ or PLA administration (22.9 +/- 2.5 vs. 23.5 +/- 3.8 min, respectively). A decrease in CORT and an increase in INS (P < 0.05) were observed with BZ before cycling. In comparison with rest, exercise resulted in a decrease in INS and an increase in all the other variables investigated (P < 0.001), but DA, NE, Epi, ACTH, CORT, La, and free fatty acid were significantly less elevated under BZ (P < 0.05). No change was found in glucose and INS levels between the two treatments at the end of the test. There was a strong correlation under both PLA and BZ conditions between DA, NE, Epi, and ACTH and also between Epi and La levels. From these data, BZ intake did appear to alter metabolism but did not influence performance during intense submaximal exercise. PMID- 8002536 TI - Effects of cocaine, benzoylecgonine, and cocaine metabolites in cannulated pressurized fetal sheep cerebral arteries. AB - Prenatal cocaine exposure has been reported to cause neurovascular complications in the developing fetus. To determine the effect of cocaine on the fetal neurovasculature, we studied the in vitro response of fetal sheep cerebral arteries to cocaine and cocaine metabolites. The change in diameter of cannulated pressurized cerebral artery segments from fetal sheep was measured using a video microscaler system. Cumulative dose-response curves (10(-12)-10(-4) M) were generated for cocaine and the major cocaine metabolites in fetal sheep cerebral artery segments. Benzoylecgonine (> 10(-10) M) also caused concentration dependent constriction, and cerebral artery segments were significantly more sensitive to benzoylecgonine than to cocaine and the other cocaine metabolites. Benzoylecgonine-induced vasoconstriction appeared to be mediated through alpha adrenergic stimulation, predominantly through stimulation of alpha 1-adrenergic receptor subtypes. We conclude that cocaine and benzoylecgonine cause significant fetal cerebral artery vasoconstriction in vitro. Cocaine and benzoylecgonine induced cerebral vasoconstriction may contribute to the perinatal neurovascular complications associated with prenatal cocaine exposure. PMID- 8002537 TI - Influence of lung volume dependence of upper airway resistance during continuous negative airway pressure. AB - To quantify the contribution of lung volume dependence of upper airway (UA) on continuous negative airway pressure (CNAP)-induced increase in upper airway resistance, we compared the changes in supralaryngeal resistance during an isolated decrease in lung volume and during CNAP in eight normal awake subjects. Inspiratory supralaryngeal resistance was measured at isoflow during four trials, during two CNAP trials where the pressure in a nasal mask was progressively decreased in 3- to 5-cmH2O steps and during two continuous positive extrathoracic pressure (CPEP) trials where the pressure around the chest (in an iron lung) was increased in similar steps. The CNAP and CPEP trials were done in random order. During the CPEP trial, the neck was covered by a rigid collar to prevent compression by the cervical seal of the iron lung. In each subject, resistance progressively increased during the experiments. The increase was linearily correlated with the pressure increase in the iron lung and with the square of the mask pressure during CNAP. There was a highly significant correlation between the rate of rise in resistance between CNAP and CPEP: the steeper the increase in resistance with decreasing lung volume, the steeper the increase in resistance with decreasing airway pressure. Lung volume dependence in UA resistance can account for 61% of the CNAP-induced increase in resistance. We conclude that in normal awake subjects the changes in supralaryngeal resistance induced by CNAP can partly be explained by the lung volume dependence of this resistance. PMID- 8002538 TI - Pulmonary vascular resistance distribution and recruitment of microvascular surface area. AB - To test the hypothesis that the distribution of hemodynamic resistance is involved in the control of pulmonary capillary surface area, we measured permeability-surface area product (PS) and longitudinal resistance distribution (LRD) as functions of perfusion rate in isolated rabbit lungs under zone II conditions (n = 10) and through the zone II-III transition (n = 4). PS, considered to be indicative of functioning capillary surface area, was measured with the aid of the diffusion-limited tracer [14C]propanediol, whereas LRD was determined using a viscous bolus technique. LRD was seen to change character with increasing flow and increasing PS/surface area, becoming bimodal with low central resistance as full capillary recruitment was approached in zone III. Effects of hypoxic ventilation were studied in zone II in five lungs; it was found that hypoxia altered the LRD and eradicated the normoxic dependence of PS/surface area on perfusion rate. It was concluded that LRD is involved in the determination of functioning capillary surface area. PMID- 8002539 TI - Effect of sleep and sighing on upper airway resistance in mongrel dogs. AB - We investigated the effect of sleep and sighing on supratracheal resistance in unrestrained mongrel dogs breathing through the nose by comparing within-breath changes in upper airway pressure-flow relationship in control, sigh, and five postsigh breaths recorded during wakefulness and during non-rapid-eye-movement and rapid-eye-movement sleep. A sigh breath was characterized by a high tidal volume and was typically followed by an apnea of a variable duration. Sleep had little or no effect on supratracheal resistance, measured at peak flow rates, during quiet breathing (awake 7.3 +/- 0.4, non-rapid eye movement 8.3 +/- 0.4, and rapid eye movement 6.8 +/- 0.4 cmH2O.l-1.s). The resistance was identical in the early part of inspiration in control and sigh breaths but increased during the augmented phase of sigh breaths. Resistance at peak inspiratory flow was higher in sigh breaths than in control breaths in all sleep states. The flow pressure profile of postsigh breaths was identical to that of control breaths in all sleep states. We conclude that upper airway resistance is essentially unaffected by sleep state in the mongrel dog and that sighing increases upper airway resistance regardless of sleep state. PMID- 8002540 TI - Energy balance at high altitude of 6,542 m. AB - Weight loss due to malnutrition and possibly intestinal malabsorption is a well known phenomenon in high-altitude climbers. Up to approximately 5,000 m, energy balance may be attained and intestinal energy digestibility remains normal. To see whether 1) energy balance may also be attained at 6,542 m and, if not, 2) whether decreased energy digestibility would play a significant role in the energy deficit, energy intake (EI), energy expenditure, body composition, and energy digestibility of 10 subjects (4 women, 6 men; 27-44 yr) were assessed during a 21-day sojourn on the summit of Mt. Sajama, Bolivia (6,542 m). EI was measured during two 3-day intervals: EI1 (days 7-9) and EI2 (days 17-19). Total fecal energy loss during EI1 was calculated from fecal energy measured by bomb calorimetry. Average daily metabolic rate (ADMR) at altitude was measured in six subjects (2 women, 4 men) using doubly labeled water over a 10-day interval (days 9-19). Basal metabolic rate was measured before and after the expedition by respiratory gas analysis. Body composition was estimated from skinfolds and body mass before and during the altitude sojourn. Subjects were in negative energy balance throughout the observation period (EI1-ADMR = -2.9 +/- 1.8 MJ/day and EI2 ADMR = -2.3 +/- 1.8 MJ/day based on a gross energy digestibility of 95%). The activity level, expressed as ADMR to basal metabolic rate, was 1.56-2.39. The loss of fat mass (3.7 +/- 1.5 kg) represented 74 +/- 15% of the loss of body mass.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8002541 TI - Pulmonary hypertension and arterial changes in calves with a systemic-to-left pulmonary artery connection. AB - The pathogenic mechanisms by which increased pressure and flow lead to pulmonary vascular disease are poorly understood, especially in newborns. To study the pathophysiological correlations and timing of the development of structural changes in response to high flow in nonhypoxic neonates, a model of high pulmonary flow was developed in newborn calves by anastomosis of the isolated left pulmonary artery (LPA) to the aorta. LPA pressure and flow increased acutely. LPA pressure reached near-systemic levels by 10 wk, whereas LPA flow was maximally increased at 1 mo before decreasing in several calves. Right pulmonary arterial pressure remained normal, and ventricular hypertrophy did not develop. Morphometric evaluation of the left lung demonstrated decreased arteriolar diameter, increased medial thickness, muscularization of arterioles at the bronchoalveolar junction, luminal obliteration of small arteries, and dilation lesions. The LPA pressure and vascular changes were greater and developed over a shorter time period than did prior models of nonhypoxic flow-induced pulmonary vascular changes. Lesser degrees of decreased arteriolar diameter and muscularization of small vessels were seen in the right lung, indicating a difference in the vascular response to moderately increased flow vs. increased pressure and flow. Thus, calves with an isolated LPA-to-aortic anastomosis simulate the hemodynamic and pulmonary vascular changes seen in newborns with congenital heart defects. Such calves may serve as models to assess effects of mechanical stresses on a newborn's vasculature. PMID- 8002542 TI - Respiratory response to inhaled CO2 during positive inspiratory pressure in humans. AB - To investigate ventilatory CO2 sensitivity during inspiratory pressure support (IPS), we administered inspiratory CO2 [fractional concn (FICO2) 0.01, 0.03, or 0.05] in eight normal subjects without (CTRL) or with (Pinsp) positive inspiratory airway pressure (5 or 10 cmH2O). At CTRL and low IPS, CO2 inhalation led to a significant increase in tidal volume (VT) with nearly identical slopes in the plot of VT vs. end-tidal PCO2. At the high IPS level, VT at FICO2 of 0 was significantly above the value at lower Pinsp and did not increase with CO2 unless FICO2 was elevated to > 0.03. There was very little effect of either Pinsp or FICO2 on respiratory frequency and respiratory timing. The data suggest that the CO2 sensitivity of ventilation is similar at low levels of IPS as during CTRL. However, at high levels of IPS, VT is determined largely by the passive inflation and, thus, independent of CO2. CO2 has to be elevated to increase the respiratory drive before VT becomes CO2 sensitive. PMID- 8002543 TI - Chest wall interrupter resistance in anesthetized paralyzed humans. AB - Tracheal (Ptr) and esophageal (Pes) pressure and flow were measured in 12 supine anesthetized paralyzed normal subjects aged 16-22 yr. The subjects were ventilated with a fixed inflation volume (range 0.57-0.62 liter) and with different constant flows ranging between 0.24 and 1.12 l/s. A rapid airway shutter (closing time 10-15 ms) was used to briefly occlude (0.4-0.9) the airways at end inspiration for 33-44 consecutive breaths. At each flow level, Ptr and Pes records obtained during end-inspiratory occlusions were ensemble averaged to allow for the cardiac artifacts. The interrupter resistances of the chest wall and respiratory system were assessed as the rapid fall in Pes and Ptr with occlusion divided by the flow preceding the occlusion. Interrupter resistances of both the chest wall and lung were independent of flow and averaged 0.4 +/- 0.1 and 1.5 +/- 0.4 (SD) cmH2O.s.l-1, respectively. The contribution of the chest wall to the total interrupter resistance was approximately 27% at flows < or = 1 l/s. PMID- 8002544 TI - Cyclooxygenase and lipoxygenase inhibition by BW-755C reduces acrolein smoke induced acute lung injury. AB - Inhalation of smoke containing acrolein, the most common toxin in urban fires after carbon monoxide, causes vascular injury with non-cardiogenic pulmonary edema containing potentially edematogenic eicosanoids such as thromboxane (Tx) B2, leukotriene (LT) B4, and the sulfidopeptide LTs (LTC4, LTD4, and LTE4). To determine which eicosanoids are important in the acute lung injury, we pretreated sheep with BW-755C (a combined cyclooxygenase and lipoxygenase inhibitor), U 63557A (a specific Tx synthetase inhibitor), or indomethacin (a cyclooxygenase inhibitor) before a 10-min exposure to a synthetic smoke containing carbon particles (4 microns) with acrolein and compared the results with those from control sheep that received only carbon smoke. Acrolein smoke induced a fall in arterial PO2 and rises in peak inspiratory pressure, main pulmonary arterial pressure, pulmonary vascular resistance, lung lymph flow, and the blood-free wet to-dry weight ratio. BW-755C delayed the rise in peak inspiratory pressure and prevented the fall in arterial PO2, the rise in lymph flow, and the rise in wet to-dry weight ratio. Neither indomethacin nor U-63557A prevented the increase in lymph flow or wet-to-dry weight ratio, although they did blunt and delay the rise in airway pressure and did prevent the rises in pulmonary arterial pressure and pulmonary vascular resistance. Thus, cyclooxygenase products, probably Tx, are responsible for the pulmonary hypertension after acrolein smoke and to some extent for the increased airway resistance but not the pulmonary edema. Prevention of high-permeability pulmonary edema after smoke with BW-755C suggests that LTB4, may be etiologic, as previous work has eliminated LTC4, LTD4, and LTE4. PMID- 8002545 TI - Hypoxia increases glucose transport at blood-brain barrier in rats. AB - Prolonged hypoxia causes several adaptive changes in systemic physiology and tissue metabolism. We studied the effects of hypobaric hypoxia on glucose transport at the blood-brain barrier (BBB) in the rat. We found that hypoxia increased the density of brain microvessels seen on immunocytochemical stains using an antibody to the glucose transporting protein GLUT. In addition, we found that hypoxia increased the density of GLUT in isolated cerebral microvessels as determined by specific cytochalasin B binding. The higher GLUT density in isolated cerebral microvessels was evident after 1 wk of hypoxia and was associated with decreased activity of gamma-glutamyltranspeptidase. Consistent with these findings, we also demonstrated that 3 wk of hypobaric hypoxia caused increased unidirectional transport of glucose at the BBB in several brain regions in vivo, as determined by the doubly labeled single-pass indicator-fractionation atrial bolus injection method in anesthetized rats. We conclude that chronic hypobaric hypoxia is associated with increased glucose transport at the BBB. PMID- 8002546 TI - Hyperbaric oxygenation increases arousal and breathing movements in fetal lambs. AB - Oxygenation produced by distending the lungs with 100% O2 increases the occurrence of arousal and fetal breathing movements (FBM), particularly during non-rapid-eye-movement (NREM) sleep, in fetal sheep of > or = 135 days of gestation. We studied the breathing and behavioral responses to a rise in arterial PO2 (PaO2) without lung distension in fetuses between 128 and 132 days of gestation. Twelve fetuses were chronically instrumented to record FBM, behavioral state, blood pressure, arterial blood gas tensions, and pH. Fetal PaO2 was raised by having the ewe breathe 100% O2 at 3 atmosphere absolute pressure spontaneously (group 1, n = 5, 129 +/- 1 days of gestation) or with mechanical ventilation to control fetal arterial PCO2 (group 2, n = 7, 131 +/- 1 days of gestation). Hyperbaric oxygenation raised fetal PaO2 by 20 Torr in both groups. During hyperbaric oxygenation, the occurrence of arousal increased severalfold in both groups. The occurrence of FBM increased during arousal in both groups, during rapid-eye-movement sleep in group 1, and during NREM sleep in group 2. The timing of diaphragmatic activity during arousal and the variability of diaphragmatic activity during NREM sleep were different than those in rapid-eye movement sleep. We conclude that oxygenation without lung distension increases the occurrence of arousal and of FBM, principally during arousal and NREM sleep, in fetuses of < or = 135 days of gestation. PMID- 8002547 TI - Pulmonary gas exchange during exercise in athletes. I. Ventilation-perfusion mismatch and diffusion limitation. AB - To investigate pulmonary gas exchange during exercise in athletes, 10 high aerobic capacity athletes (maximal aerobic capacity = 5.15 +/- 0.52 l/min) underwent testing on a cycle ergometer at rest, 150 W, 300 W, and maximal exercise (372 +/- 22 W) while trace amounts of six inert gases were infused intravenously. Arterial blood samples, mixed expired gas samples, and metabolic data were obtained. Indexes of ventilation-perfusion (VA/Q) mismatch were calculated by the multiple inert gas elimination technique. The alveolar-arterial difference for O2 (AaDO2) was predicted from the inert gas model on the basis of the calculated VA/Q mismatch. VA/Q heterogeneity increased significantly with exercise and was predicted to increase the AaDO2 by > 17 Torr during heavy and maximal exercise. The observed AaDO2 increased significantly more than that predicted by the inert gas technique during maximal exercise (10 +/- 10 Torr). These data suggest that this population develops diffusion limitation during maximal exercise, but VA/Q mismatch is the most important contributor (> 60%) to the wide AaDO2 observed. PMID- 8002549 TI - Effects of pentobarbital anesthesia on intercostal muscle activation and shortening. AB - Although pentobarbital (PB) is a commonly used anesthetic in animal studies examining respiratory motor control, there are virtually no studies that have examined the differential effects of deepening anesthesia on the activation of the various intercostal muscles. In dogs, anesthetized initially with 25 mg/kg of PB, the effects of additional doses of PB (20 mg) provided every 15 min on intercostal electromyogram (EMG) were monitored. In each animal, peak external intercostal (EI) and levator costae (LC) activation progressively decreased with additional doses of PB and were eventually abolished, at which point peak parasternal (PA) EMG had increased to 127 +/- 13% (SE) of control values; peak diaphragm EMG was unaffected. The reductions in EI activation were associated with progressive reductions in EI muscle shortening that, in turn, were associated with progressive reductions in lateral rib cage expansion. PA shortening was not significantly affected. Similar results were obtained in animals breathing supplemental oxygen. These results indicate that 1) activation of EI and LC compared with PA have divergent responses, with EI and LC decreasing and PA increasing; 2) the fall in EI activation results in decrements in EI shortening and lateral rib cage motion; and 3) anesthetic depth is an important variable that must be controlled in studies assessing intercostal muscle activation. PMID- 8002548 TI - Upper airway collapsibility in children with obstructive sleep apnea syndrome. AB - In adults, the critical nasal pressure (Pcrit) at which the upper airway collapses is higher in patients with the obstructive sleep apnea syndrome (OSAS) than in those with primary snoring. Pediatric OSAS differs clinically from adult OSAS. We therefore compared Pcrit between prepubertal children with OSAS and primary snoring. Pcrit was determined by correlating the maximal inspiratory airflow with the level of positive or negative nasal pressure applied via a nasal mask. As in adults, we found that the maximal inspiratory airflow varied in proportion to the upstream (nasal) rather than the downstream (esophageal) pressure changes. Pcrit was 1 +/- 3 cmH2O in OSAS compared with -20 +/- 9 cmH2O in primary snorers (P < 0.002). In three OSAS patients reevaluated after tonsillectomy and adenoidectomy, Pcrit declined to -7.2 +/- 4.0 cmH2O. We conclude that the pediatric airway behaved as predicted by the Starling resistor model and that Pcrit, a measure of airway collapsibility, correlated with the degree of upper airway obstruction and was reduced postoperatively, consistent with increased upper airway stability. PMID- 8002550 TI - Lower limit of body fat in healthy active men. AB - We examined body composition changes in 55 normal young men during an 8-wk Army combat leadership training course involving strenuous exercise and low energy intake, with an estimated energy deficit of 5.0 +/- 2.0 MJ/day and a resultant 15.7 +/- 3.1% weight loss. Percent body fat (BF) measured by dual-energy X-ray absorptiometry (DEXA) averaged 14.3% (range 6-26%) and 5.8 +/- 1.8% (range 4-11%) at the beginning and end of the course, respectively. Men who achieved a minimum percent BF (4-6%) by 6 wk demonstrated only small additional total and subcutaneous fat losses in the final 2 wk and sacrificed increasingly larger proportions of fat-free mass. Percent BF estimated from skinfold thicknesses reflected relative changes in fat mass, although actual percent BF was overestimated. Instead of reaching a plateau after fat stores were substantially depleted, abdominal, hip, and thigh girths continued to decline with body weight loss. Final percent BF for the leanest men was similar to that observed after a 25% body weight reduction in the 1950 Minnesota study (5.2% by underwater weighting), and height-corrected final fat mass was the same (1.0 +/- 0.2 vs. 0.9 +/- 0.7 kg fat/m2), suggesting that these values represent a minimal body fat content in healthy men and that weight loss subsequent to achieving this level is contributed from the fat-free mass. Our results suggest that 4-6% BF or approximately 2.5 kg fat represents the lower limit for healthy men, as assessed by DEXA or by underwater weighing. PMID- 8002551 TI - Catecholamine responses to short-term high-intensity resistance exercise overtraining. AB - Seventeen weight-trained males were divided into an overtraining group [OT; n = 11; age = 22.0 +/- 0.9 (SE) yr] that weight trained their legs daily for 2 wk with 100% 1 repetition maximum relative intensity on a squat machine and a control group (n = 6; age = 23.7 +/- 2.4 yr) that exercised 1 day/wk with low relative intensity (50% 1 repetition maximum). Test batteries including strength assessments and resting and exercise-induced concentrations of epinephrine and norepinephrine were conducted at the beginning, middle, and end (tests 1-3, respectively) of the study. Strength capabilities decreased by test 3 for the OT group (P < 0.05). Resting catecholamine concentrations did not change for either group during the study, whereas exercise-induced concentrations of both epinephrine (test 1 = 3,407.9 +/- 666.6 pmol/l, test 2 = 7,563.7 +/- 1,210.6 pmol/l, test 3 = 6,931.6 +/- 919.3 pmol/l) and norepinephrine (test 1 = 42.9 +/- 7.4 nmol/l, test 2 = 70.0 +/- 8.8 nmol/l, test 3 = 85.2 +/- 14.5 nmol/l) significantly increased by tests 2 and 3 for only the OT group. Correlation coefficients suggested decreased responsitivity of skeletal muscle to sympathetic nervous system activity. It appears that altered exercise-induced sympathetic nervous system activity accompanies high relative intensity resistance exercise overtraining and may be among the initial responses to the onset of the previously theoretical sympathetic overtraining syndrome. PMID- 8002552 TI - Interactive effects of emphysema and malnutrition on diaphragm structure and function. AB - Interactive effects of emphysema (EMP) and prolonged nutritional deprivation (ND) on contractile, morphometric, and metabolic properties of hamster diaphragm muscle (DIA) were examined. Six months after induction of EMP (intratracheal elastase), saline-treated controls (CTL) and EMP hamsters of similar body weights were subjected to ND over 6 wk. Isometric contractile and fatigue properties of costal DIA were determined in vitro. DIA fibers were histochemically classified as type I or II, and fiber succinate dehydrogenase activity and cross-sectional area were determined using quantitative microscopic procedures. From histochemical sections, the number of capillaries per fiber (C/F) and per fiber cross-sectional area (C/A) were determined. ND resulted in progressive loss of body weight (ND-CTL, 23.8%; ND-EMP, 28.4%; P = NS). ND did not affect reduction in optimal length (Lo) of DIA fibers in EMP compared with CTL and ND-CTL hamsters. Maximum specific force (i.e., force/unit area) was reduced by approximately 25% in EMP animals compared with CTL. ND did not improve or exacerbate the reduction in specific force with EMP. ND attenuated improved fatigue resistance of DIA in EMP animals. No differences in fiber type proportions were noted among experimental groups. Significant atrophy of type I and II DIA fibers was noted after ND. Atrophy was proportionately greater in type II fibers of ND-EMP when referenced to EMP animals. Thus adaptive hypertrophy of type II DIA fibers in EMP animals was abolished. Fiber succinate dehydrogenase activity was significantly increased in type I and II fibers in EMP DIA. ND did not affect this metabolic adaptation of DIA fibers to persistent loads imposed by EMP.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8002553 TI - High physiological levels of epinephrine do not enhance muscle glycogenolysis during tetanic stimulation. AB - This study examined whether high physiological concentrations of epinephrine (EPI) would enhance muscle glycogenolysis during intense muscular contractions. Muscles of the rat hindlimb were perfused for 12 min at rest and 45 s of tetanic stimulation (1.0-Hz train rate, 100-ms train duration at 80 Hz) without EPI (control) or with 15 or 35 nM EPI. In the EPI groups the muscles were perfused with EPI for the last 2 min of rest perfusion and throughout stimulation. Glycogenolysis in the white gastrocnemius, red gastrocnemius, plantaris, and soleus muscles during stimulation was unaffected by the presence of EPI in the perfusion medium. In addition, muscle lactate and hindlimb lactate efflux were similar in EPI and control groups. It is concluded that EPI is not important for enhancing glycogenolysis in rat muscles composed predominantly of fast-twitch fibers during intense short-term tetanic stimulation. PMID- 8002555 TI - Surface activity of lipid extract surfactant in relation to film area compression and collapse. AB - The physical properties of modified porcine surfactant (Curosurf), isolated from minced lungs by extraction with chloroform-methanol and further purified by liquid-gel chromatography, were investigated with the captive bubble technique. Bubble size, and thus the surface tension of an insoluble film at the bubble surface, is altered by changing the pressure within the closed bubble chamber. The film surface tension and area are determined from the shape (height and diameter) of the bubble. Adsorption of fresh Curosurf is characterized by stepwise decreases in surface tension, which can easily be observed by sudden quick movements of the bubble apex. These "adsorption clicks" imply a cooperative movement of large collective units of molecules, approximately 10(14) (corresponding to approximately 120 ng of phospholipid) or approximately 10(18) molecules/m2, into the interface during adsorption. Films formed in this manner are already highly enriched in dipalmitoyl phosphatidylcholine, as seen by the extremely low compressibility, close to that of dipalmitoyl phosphatidylcholine. Near-zero minimum tensions are obtained, even at phospholipid concentrations as low as 50 micrograms/ml. During dynamic cycling (20-50 cycles/min), low minimum surface tensions, good film stability, low compressibility, and maximum surface tensions between 30 and 40 mN/m are possible only if the films are not overcompressed near zero surface tension; i.e., the overall film area compression should not substantially exceed 30%. PMID- 8002554 TI - Lung volumes and expiratory flow limitation during exercise in interstitial lung disease. AB - Lung volumes were measured at rest and during exercise by an open-circuit N2 washout technique in patients with interstitial lung disease (ILD). Exercise tidal flow-volume (F-V) curves were also compared with maximal F-V curves to investigate whether these patients demonstrated flow limitation. Seven patients underwent 4 min of constant work rate bicycle ergometer exercise at 40, 70, and 90% of their previously determined maximal work rates. End-expiratory lung volume and total lung capacity were measured at rest and near the end of each period of exercise. There was no significant change in end-expiratory lung volume or total lung capacity when resting measurements were compared with measurements at 40, 70, and 90% work rates. During exercise, expiratory flow limitation was evident in four patients who reported stopping exercise because of dyspnea. In the remaining patients who discontinued exercise because of leg fatigue, no flow limitation was evident. In all patients, the mean ratio of maximal minute ventilation to maximal ventilatory capacity (calculated from maximal F-V curves) was 67%. We conclude that lung volumes during exercise do not significantly differ from those at rest in this population and that patients with ILD may demonstrate expiratory flow limitation during exercise. Furthermore, because most patients with ILD are not breathing near their maximal ventilatory capacity at the end of exercise, we suggest that respiratory mechanics are not the primary cause of their exercise limitation. PMID- 8002556 TI - Index finger position and force of the human first dorsal interosseus and its ulnar nerve antagonist. AB - In normal subjects, maximum voluntary contraction (MVC) and electrical ulnar nerve stimulation (UNS; 30-Hz bursts of 0.33 s) were systematically compared with regard to the forces generated in different directions (abduction/adduction and flexion) and at different degrees of index finger abduction. With a "resting" hand position in which there was no index finger abduction, UNS produced about one-half of the abduction force elicited by an MVC (mean ratio 51%). Qualitatively, such a discrepancy would be expected, because UNS activates two index finger muscles with opposing actions in the abduction/adduction plane of torques: the first dorsal interosseus (FDI) and the first palmar interosseus (FPI). The abduction forces produced by MVC and UNS were very sensitive to index finger abduction angle: at a maximum degree of abduction, the UNS-generated force even reversed its direction of action to adduction (with FPI dominating) and the abduction MVC declined to 37% of that in the resting hand position. Inasmuch as these declines in MVC- and UNS-generated abduction force could not be explained by a change in moment arm, the main alternative seemed to be abduction-associated alterations in FDI fiber length (analysis by previously published biomechanical data). The FDI and FPI were further compared by application of a UNS-generated fatigue test (5-min burst stimulation), with the index finger kept at a "neutral" angle, i.e., the abduction angle at which, in the unfatigued state, the forces of the FDI and FPI were in balance (zero net UNS-generated abduction/adduction force).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8002557 TI - Cardiopulmonary adaptations to pneumonectomy in dogs. IV. Membrane diffusing capacity and capillary blood volume. AB - Lung diffusing capacity for carbon monoxide (DLco) and its components, membrane diffusing capacity (Dmco) and capillary blood volume (Vc), as well as pulmonary blood flow (Qc), were measured at rest at several lung volumes and during treadmill exercise by a rebreathing technique in four adult dogs after right pneumonectomy (R-PNX) and in six matched control dogs (Sham) 6-12 mo after surgery. In both groups, lung inflation at rest was associated with a small increase in DLco and Dmco but not in Vc. After R-PNX, total DLco was lower by 30% at peak exercise compared with control values. When compared with DLco in a normal left lung, DLco in the remaining lung continued to increase along the normal relationship with respect to Qc up to a cardiac output equivalent to 34 l/min through both lungs of the Sham dog. There was no evidence of an upper limit of DLco being reached. The augmentation of DLco from rest to exercise was associated with corresponding increases in Dmco and Vc; after R-PNX, both Dmco and Vc continued to increase with respect to Qc along similar relationships as in control dogs without reaching an upper limit, suggesting a much larger alveolar capillary reserve for gas exchange by diffusion than previously recognized. At higher levels of blood flow through the remaining lung, DLco was greater in adult dogs after R-PNX than after left pneumonectomy (Carlin et al. J. Appl. Physiol. 70: 135-142, 1991), suggesting that additional sources of compensation, e.g., lung growth, exist after removal of > 50% of lung. PMID- 8002558 TI - Critical incident stress and the medical photographer: its causes and effects. PMID- 8002559 TI - Health hazards in the biocommunications department. PMID- 8002560 TI - "Neurofibromatosis: von Recklinghausen disease". PMID- 8002561 TI - How dermatologists perceive CRT displays and silver halide prints of transparency based images: a comparison study. PMID- 8002563 TI - The mutation DGT1-1 decreases glucose transport and alleviates carbon catabolite repression in Saccharomyces cerevisiae. AB - Glucose in ethanol-glycerol mixtures inhibits growth of Saccharomyces cerevisiae mutants lacking phosphoglycerate mutase. A suppressor mutation that relieved glucose inhibition was isolated. This mutation, DGT1-1 (decreasing glucose transport), was dominant and produced pleiotropic effects even in an otherwise wild-type background. Growth of the DGT1-1 mutant in glucose was dependent on respiration, and no ethanol was detected in the medium within 7 h of glucose addition. When grown on glucose, the mutant had a reduced glucose uptake and both the low- and high-affinity transport systems were affected. In galactose-grown cells, only the high-affinity glucose transport system was detected. This system had similar kinetic characteristics in the wild type and in the mutant. Catabolite repression of several enzymes was absent in the mutant during growth in glucose but not during growth in galactose. In contrast with the wild type, the mutant grown in glucose had high transcription of the glucose transporter gene SNF3 and no transcription of HXT1 and HXT3. Expression of multicopy plasmids carrying the HXT1, HXT2, or HXT3 gene allowed partial recovery of both fermentative capacity and catabolite repression in the mutant. The results suggest that DGT1 codes for a regulator of the expression of glucose transport genes. They also suggest that glucose flux might determine the levels of molecules implicated as signals in catbolite repression. PMID- 8002562 TI - Physical and genetic map of Streptococcus thermophilus A054. AB - The three restriction endonucleases SfiI, BssHII, and SmaI were found to generate fragments with suitable size distributions for mapping the genome of Streptococcus thermophilus A054. A total of 5, 8, and 24 fragments were produced with SfiI, BssHII, and SmaI, respectively. An average genome size of 1,824 kb was determined by summing the total fragment sizes obtained by digestions with these three enzymes. Partial and multiple digestions of genomic DNA in conjunction with Southern hybridization were used to map SfiI, BssHII, and SmaI fragments. All restriction fragments were arranged in a unique circular chromosome. Southern hybridization analysis with specific probes allowed 23 genetic markers to be located on the restriction map. Among them, six rrn loci were precisely located. The area of the chromosome containing the ribosomal operons was further detailed by mapping some of the ApaI and SgrAI sites. Comparison of macrorestriction patterns from three clones derived from strain A054 revealed two variable regions in the chromosome. One was associated with the tandem rrnD and rrnE loci, and the other was mapped in the region of the lactose operon. PMID- 8002565 TI - Novel ionizing radiation-sensitive mutants of Deinococcus radiodurans. AB - Two new loci, irrB and irrI, have been identified in Deinococcus radiodurans. Inactivation of either locus results in a partial loss of resistance to ionizing radiation. The magnitude of this loss is locus specific and differentially affected by inactivation of the uvrA gene product. An irrB uvrA double mutant is more sensitive to ionizing radiation than is an irrB mutant. In contrast, the irrI uvrA double mutant and the irrI mutant are equally sensitive to ionizing radiation. The irrB and irrI mutations also reduce D. radiodurans resistance to UV radiation, this effect being most pronounced in uvrA+ backgrounds. Subclones of each gene have been isolated, and the loci have been mapped relative to each other. The irrB and irrI genes are separated by approximately 20 kb of intervening sequence that encodes the uvrA and pol genes. PMID- 8002564 TI - Mutations affecting two adjacent amino acid residues in the alpha subunit of RNA polymerase block transcriptional activation by the bacteriophage P2 Ogr protein. AB - The bacteriophage P2 ogr gene product is a positive regulator of transcription from P2 late promoters. The ogr gene was originally defined by compensatory mutations that overcame the block to P2 growth imposed by a host mutation, rpoA109, in the gene encoding the alpha subunit of RNA polymerase. DNA sequence analysis has confirmed that this mutation affects the C-terminal region of the alpha subunit, changing a leucine residue at position 290 to a histidine (rpoAL290H). We have employed a reporter plasmid system to screen other, previously described, rpoA mutants for effects on activation of a P2 late promoter and have identified a second allele, rpoA155, that blocks P2 late transcription. This mutation lies just upstream of rpoAL290H, changing the leucine residue at position 289 to a phenylalanine (rpoAL289F). The effect of the rpoAL289F mutation is not suppressed by the rpoAL290H-compensatory P2 ogr mutation. P2 ogr mutants that overcome the block imposed by rpoAL289F were isolated and characterized. Our results are consistent with a direct interaction between Ogr and the alpha subunit of RNA polymerase and support a model in which transcription factor contact sites within the C terminus of alpha are discrete and tightly clustered. PMID- 8002566 TI - Isolation and partial characterization of Borrelia burgdorferi inner and outer membranes by using isopycnic centrifugation. AB - In order to characterize the protein composition of the outer membrane of Borrelia burgdorferi, we have isolated inner and outer membranes by using discontinuous sucrose density step gradients. Outer and inner membrane fractions isolated by this method contained less than 1 and 2%, respectively, of the total lactate dehydrogenase activity (soluble marker) in cell lysate. More importantly, the purified outer membranes contained less than 4% contamination by the C subunit of F1/F0 ATPase (inner membrane marker). Very little flagellin protein was present in the outer membrane sample. This indicated that the outer membranes were relatively free of contamination by cytoplasmic, inner membrane or flagellar components. The outer membrane fractions (rho = 1.19 g/cm3) contained 0.15 mg (dry weight) of protein per mg. Inner membrane samples (rho = 1.12 g/cm3) contained 0.60 mg (dry weight) of protein per mg. Freeze-fracture electron microscopy revealed that the outer membrane vesicles contained about 1,700 intramembranous particles per micron 2 while inner membrane densities for inner and outer membranes. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and nonequilibrium pH gel electrophoresis-SDS-PAGE analyses of inner and outer membrane samples revealed several proteins unique to the inner membrane and 20 proteins that localized specifically to the outer membrane. This analysis clearly shows that the inner and outer membranes isolated by this technique are unique structures. PMID- 8002568 TI - Oxidative release of nitrite from 2-nitrotoluene by a three-component enzyme system from Pseudomonas sp. strain JS42. AB - Pseudomonas sp. strain JS42 utilizes 2-nitrotoluene (2NT) as the sole source of carbon and energy for growth. Intact cells catalyze the oxidation of 2NT to 3 methylcatechol and nitrite in a reaction that requires molecular oxygen. Cell extracts oxidized 2NT to 3-methylcatechol and nitrite in the presence of NAD(P)H and ferrous iron. Ion-exchange chromatography yielded three protein fractions (A, B, and C) which were all required for the oxidation of 2NT to 3-methylcatechol and nitrite. Component B (reductase2NT) catalyzed a NAD(P)H-dependent reduction of cytochrome c. Solutions of component A (ISP2NT) were brown and showed absorption maxima at 458 and 324 nm. Two major bands with M(r)s 52,500 and 28,000 were observed when ISP2NT was analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Component C could be replaced by ferredoxin NAP from the Pseudomonas putida NCIB 9816-4 naphthalene dioxygenase system and was given the designation ferredoxin2NT. Experiments with 18O2 showed that both oxygen atoms were added to the aromatic ring of 2NT to yield 3-methylcatechol. The enzyme is a new multicomponent enzyme system which we have designated 2NT 2,3-dioxygenase. PMID- 8002567 TI - Cloning, sequencing, and expression in Escherichia coli of the Bacillus subtilis gene for phosphatidylserine synthase. AB - The Bacillus subtilis pss gene encoding phosphatidylserine synthase was cloned by its complementation of the temperature sensitivity of an Escherichia coli pssA1 mutant. Nucleotide sequencing of the clone indicated that the pss gene encodes a polypeptide of 177 amino acid residues (deduced molecular weight of 19,613). This value agreed with the molecular weight of approximately 18,000 observed for the maxicell product. The B. subtilis phosphatidylserine synthase showed 35% amino acid sequence homology to the yeast Saccharomyces cerevisiae phosphatidylserine synthase and had a region with a high degree of local homology to the conserved segments in some phospholipid synthases and amino alcohol phosphotransferases of E. coli and S. cerevisiae, whereas no homology was found with that of the E. coli counterpart. A hydropathy analysis revealed that the B. subtilis synthase is very hydrophobic, in contrast to the hydrophilic E. coli counterpart, consisting of several strongly hydrophobic segments that would span the membrane. A manganese dependent phosphatidylserine synthase activity, a characteristic of the B. subtilis enzyme, was found exclusively in the membrane fraction of E. coli (pssA1) cells harboring a B. subtilis pss plasmid. Overproduction of the B. subtilis synthase in E. coli cells by a lac promoter system resulted in an unusual increase of phosphatidylethanolamine (up to 93% of the total phospholipids), in contrast to gratuitous overproduction of the E. coli counterpart. This finding suggested that the unusual cytoplasmic localization of the E. coli phosphatidylserine synthase plays a role in the regulation of the phospholipid polar headgroup composition in this organism. PMID- 8002569 TI - Genetic evidence that the gacA gene encodes the cognate response regulator for the lemA sensor in Pseudomonas syringae. AB - Mutational analysis of the bean-pathogenic Pseudomonas syringae pv. syringae strain B728a has led to the genetic identification of the gacA gene as encoding the response regulator for the unlinked lemA sensor kinase. The analysis of a collection of spontaneous mutants of P. syringae pv. syringae suggested that the gacA gene was involved in lesion formation and the production of protease and syringomycin. The gacA gene originally was identified as a regulator of extracellular antibiotic production by Pseudomonas fluorescens, and the predicted GacA protein is a member of the FixJ family of bacterial response regulators. The sequence of the putative B728a GacA protein revealed 92% identity with the P. fluorescens GacA protein. An insertional mutation within the P. syringae pv. syringae gacA gene abrogated lesion formation on beans, production of extracellular protease, and production of the toxin syringomycin, the same phenotypes affected by a lemA mutation. DNA sequence analysis identified the P. syringae pv. syringae uvrC gene immediately downstream of the gacA gene, an arrangement conserved in P. fluorescens and Escherichia coli. The gacA insertional mutant was sensitive to UV, presumably because of polarity on transcription of the downstream uvrC gene. Southwestern (DNA-protein) analysis revealed that the lemA and gacA genes were required for the full expression of a DNA binding activity. PMID- 8002570 TI - The URE2 protein regulates nitrogen catabolic gene expression through the GATAA containing UASNTR element in Saccharomyces cerevisiae. AB - Many of the gene products that participate in nitrogen metabolism are sensitive to nitrogen catabolite repression (NCR), i.e., their expression is decreased to low levels when readily used nitrogen sources such as asparagine are provided. Previous work has shown this NCR sensitivity requires the cis-acting UASNTR element and trans-acting GLN3. Here, we extend the analysis to include the response of their expression to deletion of the URE2 locus. The expression of these nitrogen catabolic genes becomes, to various degrees, NCR insensitive in the ure2 deletion. This response is shown to be mediated through the GATAA containing UASNTR element and supports the current idea that the NCR regulatory circuit involves the following steps: environmental signal-->URE2-->GLN3-->UASNTR operation-->NCR-sensitive gene expression. The various responses of the nitrogen catabolic genes' expression to deletion of the URE2 locus also indicate that not all NCR is mediated through URE2. PMID- 8002571 TI - Molecular cloning and sequencing of an operon, carRS of Azospirillum brasilense, that codes for a novel two-component regulatory system: demonstration of a positive regulatory role of carR for global control of carbohydrate catabolism. AB - A pleiotropic carbohydrate mutant, CR17, of Azospirillum brasilense RG (wild type) that assimilates C4 dicarboxylates (succinate and malate) but not carbohydrate (fructose, arabinose, galactose, glycerol, and gluconate) as C sources for growth was used to identify the car (carbohydrate regulation) locus by complementation analysis. The 2.8-kb genomic fragment that complemented the Car- defect of CR17 and overlapped the fru operon (S. Chattopadhyay, A. Mukherjee, and S. Ghosh, J. Bacteriol. 175:3240-3243, 1993) has now been completely sequenced. The sequence contains an operon, carRS, coding for two proteins, CARR and CARS, having 236 and 352 amino acid residues, respectively. The 3'-flanking region of the carRS operon showed sequence homology with the 5' terminus of the fruB gene of a related bacterium, Rhodobacter capsulatus. A complementation study with carRS deletion clones showed that only the carR+ gene was required to complement the Car- defect of CR17, signifying that the carbohydrate pleiotropy was due to a lesion within this gene. Although the 2.8-kb DNA containing the carRS operon when introduced by conjugation into CR17 also complemented the Car- defect, the complemented transconjugant was unable to utilize succinate as a C source. The reason for this is not clear. A sequence analysis of the two protein products strongly suggests that the protein pair may constitute a novel two-component regulatory system for global expression of carbohydrate catabolic pathways in A. brasilense. PMID- 8002572 TI - Physical characterization of the flagella and flagellins from Methanospirillum hungatei. AB - Flagellar filaments from Methanospirillum hungatei GP1 and JF1 were isolated and subjected to a variety of physical and chemical treatments. The filaments were stable to temperatures up to 80 degrees C and over the pH range of 4 to 10. The flagellar filaments were dissociated in the detergents (final concentration of 0.5%) Triton X-100, Tween 20, Tween 80, Brij 58, N-octylglucoside, cetyltrimethylammonium bromide, and Zwittergent 3-14, remaining intact in only two of the detergents tested, sodium deoxycholate and 3-[(3-cholamidopropyl) dimethyl-ammonio]-1-propanesulfonate (CHAPS). Spheroplasting techniques were used to separate the internal cells from the complex sheath, S-layer (cell wall), and end plugs of M. hungatei. The flagellar basal structure was visualized after solubilization of membranes by CHAPS or deoxycholate. The basal structure appeared to be a simple knob with no apparent ring or hook structures. The multiple, glycosylated flagellins constituting the flagellar filaments were cleaved by proteases and cyanogen bromide. The cyanogen bromide-generated fragments of M. hungatei GP1 flagellins were partially sequenced to provide internal sequence information. In addition, the amino acid composition of each flagellin was determined and indicated that the flagellins are distinct gene products, rather than differentially glycosylated forms of the same gene product. PMID- 8002573 TI - Phosphorylation of cytadherence-accessory proteins in Mycoplasma pneumoniae. AB - Attachment to host cells of the respiratory epithelium by Mycoplasma pneumoniae is a complex, multicomponent process, requiring a number of accessory proteins in addition to adhesins directly involved in receptor binding. In this study, protein phosphorylation of the cytadherence-accessory proteins HMW1, HMW2, and HMW4 of M. pneumoniae was examined using biochemical and immunological techniques. The initial indication of protein modification came from Western immunoblot analysis of the two-dimensional polyacrylamide gel electrophoresis (PAGE) profile of M. pneumoniae proteins, revealing multiple spots for both HMW1 and HMW4 that varied in pI but not in size. M. pneumoniae cultured in the presence of H3(32)PO4 exhibited numerous phosphorylated proteins as detected by sodium dodecyl sulfate-PAGE and autoradiography. These included proteins corresponding to HMW1, HMW2, and HMW4 in electrophoretic mobility. The Triton X 100 partitioning characteristics of these phosphorylated proteins was identical to that described previously for HMW1, -2, and -4. Furthermore, these protein bands were absent when a noncytadhering variant deficient in HMW1-5 was examined in the same manner. Finally, the availability of antiserum to HMW1 and -4 enabled us to confirm by radioimmunoprecipitation that HMW1 and HMW4 are phosphoproteins. Phosphoamino acid analysis of acid-hydrolyzed HMW1 and HMW2 identified primarily phosphothreonine and, to a lesser extent, phosphoserine in HMW1 and predominantly phosphoserine, with a trace of phosphothreonine, in HMW2. Neither protein contained phosphotyrosine. HMW1-HMW5 are components of a cytoskeleton-like structure in M. pneumoniae that is thought to function in cell division, changes in cell morphology, gliding motility, and the localization of adhesins in the mycoplasma membrane. Phosphorylation may regulate cytoskeleton dynamics involving these cytadherence-accessory proteins. PMID- 8002574 TI - Interplasmidic recombination following irradiation of the radioresistant bacterium Deinococcus radiodurans. AB - Deinococcus radiodurans R1 and other members of the eubacterial family Deinococcaceae are extremely resistant to ionizing radiation and many other agents that damage DNA. For example, after irradiation, D. radiodurans can repair > 100 DNA double-strand breaks per chromosome without lethality or mutagenesis, while most other organisms can survive no more than 2 or 3 double-strand breaks. The unusual resistance of D. radiodurans is recA dependent, but the repair pathway(s) is not understood. Recently, we described how a plasmid present in D. radiodurans (plasmid copy number, approximately 6 per cell; chromosome copy number, approximately 4 per cell) during high-dose irradiation undergoes extreme damage like the chromosome and is retained by the cell without selection and fully repaired with the same efficiency as the chromosome. In the current work, we have investigated the repair of two similar plasmids within the same cell. These two plasmids were designed to provide both restriction fragment polymorphisms and a drug selection indicator of recombination. This study presents a novel system of analysis of in vivo damage and recombinational repair, exploiting the unique ability of D. radiodurans to survive extraordinarily high levels of DNA damage. We report that homologous recombination among plasmids following irradiation is extensive. For example, 2% of Tcs plasmids become Tcr as a result of productive recombination within a 929-bp region of the plasmids after repair. Our results suggest that each plasmid may participate in as many as 6.7 recombinational events during repair, a value that extrapolates to > 700 events per chromosome undergoing repair simultaneously. These results indicate that the study of plasmid recombination within D. radiodurans may serve as an accurate model system for simultaneously occurring repair in the chromosome. PMID- 8002575 TI - A mutant lacking the glutamine synthetase gene (glnA) is impaired in the regulation of the nitrate assimilation system in the cyanobacterium Synechocystis sp. strain PCC 6803. AB - The existence in the unicellular cyanobacterium Synechocystis sp. strain PCC 6803 of two genes (glnA and glnN) coding for glutamine synthetase (GS) has been recently reported (J.C. Reyes and F.J. Florencio, J. Bacteriol. 176:1260-1267, 1994). In the current work, the regulation of the nitrate assimilation system was studied with a glnA-disrupted Synechocystis mutant (strain SJCR3) in which the only GS activity is that corresponding to the glnN product. This mutant was unable to grow in ammonium-containing medium because of its very low levels of GS activity. In the SJCR3 strain, nitrate and nitrite reductases were not repressed by ammonium, and short-term ammonium-promoted inhibition of nitrate uptake was impaired. In Synechocystis sp. strain PCC 6803, nitrate seems to act as a true inducer of its assimilation system, in a way similar to that proposed for the dinitrogen-fixing cyanobacteria. A spontaneous derivative strain from SJCR3 (SJCR3.1), was able to grow in ammonium-containing medium and exhibited a fourfold-higher level of GS activity than but the same amount of glnN transcript as its parental strain (SJCR3). Taken together, these finding suggest that SJCR3.1 is a mutant affected in the posttranscriptional regulation of the GS encoded by glnN. This strain recovered regulation by ammonium of nitrate assimilation. SJCR3 cells were completely depleted of intracellular glutamine shortly after addition of ammonium to cells growing with nitrate, while SJCR3.1 cells maintained glutamine levels similar to that reached in the wild-type Synechocystis sp. strain PCC 6803. Our results indicate that metabolic signals that control the nitrate assimilation system in Synechocystis sp. strain PCC 6803 require ammonium metabolism through GS. PMID- 8002576 TI - Hyperrecombination in the terminus region of the Escherichia coli chromosome: possible relation to nucleoid organization. AB - The terminus region of the Escherichia coli chromosome is the scene of frequent homologous recombination. This can be demonstrated by formation of deletions between directly repeated sequences which flank a genetic marker whose loss can be easily detected. We report here that terminal recombination events are restricted to a relatively large terminal recombination zone (TRZ). On one side of the TRZ, the transition from the region with a high excision rate to the normal (low) excision rates of the rest of the chromosome occurs along a DNA stretch of less than 1 min. No specific border of this domain has been defined. To identify factors inducing terminal recombination, we examined its relation to two other phenomena affecting the same region, site-specific recombination at the dif locus and site-specific replication pausing. Both the location and the efficiency of terminal recombination remained unchanged after inactivation of the dif-specific recombination system. Similarly, inactivation of site-specific replication pausing or displacement of the replication fork trap so that termination occurs about 200 kb away from the normal region had no clear effect on this phenomenon. Therefore, terminal recombination is not a direct consequence of either dif-specific recombination or replication termination. Furthermore, deletions encompassing the wild-type TRZ do not eliminate hyperrecombination. Terminal recombination therefore cannot be attributed to the activity of some unique sequence of the region. A possible explanation of terminal hyperrecombination involves nucleoid organization and its remodeling after replication: we propose that post replicative reconstruction of the nucleoid organization results in a displacement of the catenation links between sister chromosomes to the last chromosomal domain to be rebuilt. Unrelated to replication termination, this process would facilitate interactions between the catenated molecules and would make the domain highly susceptible to recombination between sister chromosomes. PMID- 8002577 TI - The vfr gene product, required for Pseudomonas aeruginosa exotoxin A and protease production, belongs to the cyclic AMP receptor protein family. AB - The synthesis of exotoxin A (ETA) by Pseudomonas aeruginosa is a complex, regulated event. Several ETA putative regulatory mutants of P. aeruginosa PA103 have previously been characterized (S. E. H. West, S. A. Kaye, A. N. Hamood, and B. H. Iglewski, Infect. Immun. 62:897-903, 1994). In addition to ETA production, these mutants, PA103-15, PA103-16, and PA103-19, were also deficient in the production of protease and in regA P1 promoter activity. RegA is a positive regulator of ETA transcription. We cloned a gene, designated vfr for virulence factor regulator, that restored ETA and protease production to parental levels in these mutants. In addition, transcription from the regA P1 promoter was restored. In Escherichia coli, when vfr was overexpressed from a phage T7 promoter, a protein with an apparent molecular mass of 28.5 kDa was produced. Analysis of the deduced amino acid sequence of vfr revealed that the expected protein is 67% identical and 91% similar over a 202-amino-acid overlap to the E. coli cyclic AMP receptor protein (CAP or Crp). The cloned vfr gene complemented the beta galactosidase- and tryptophanase-deficient phenotypes of E. coli RZ1331, a crp deletion mutant. However, the E. coli crp gene under the control of the tac promoter did not complement the ETA-deficient or protease-deficient phenotype of PA103-15 or PA103-16. The ability of vfr to restore both ETA and protease production to these mutants suggests that vfr is a global regulator of virulence factor expression in P. aeruginosa. PMID- 8002578 TI - Characterization of devA, a gene required for the maturation of proheterocysts in the cyanobacterium Anabaena sp. strain PCC 7120. AB - Mutant M7, obtained by transposon mutagenesis of the cyanobacterium Anabaena sp. strain PCC 7120, is impaired in the development of mature heterocysts. Under aerobic conditions, the mutant is unable to fix N2 because of a deficiency of at least two components of the oxygen-protective mechanisms: a hemoprotein-coupled oxidative reaction and heterocyst-specific glycolipids. DNA contiguous with the inserted transposon was recovered from the mutant and sequenced. The transposon had inserted itself within a 732-bp open reading frame designated devA. The wild type form of devA, obtained from a lambda-EMBL3 library of Anabaena sp. DNA, had the identical sequence. Directed mutagenesis of devA in the wild-type strain showed that the phenotype of the mutant was caused by insertion of the transposon. The wild-type form of devA on a shuttle vector complemented the mutation in M7. Expression of devA by whole filaments, monitored following nitrogen stepdown by using luxAB as the reporter, increased ca. eightfold during differentiation; the increase within differentiating cells was much greater. The deduced sequence of the DevA protein shows strong similarity to the ATP-binding subunit of binding protein-dependent transport systems. The product of devA may, therefore, be a component of a periplasmic permease that is required for the transition from a proheterocyst to a mature, nitrogen-fixing heterocyst. PMID- 8002579 TI - An aromatic effector specificity mutant of the transcriptional regulator DmpR overcomes the growth constraints of Pseudomonas sp. strain CF600 on para substituted methylphenols. AB - The pVI150 catabolic plasmid of Pseudomonas sp. strain CF600 carries the dmp system, which comprises the divergently transcribed dmpR gene and the dmp operon coding for the catabolic enzymes required for growth on (methyl)phenols. The constitutively expressed DmpR transcriptional activator positively controls the expression of the RpoN-dependent dmp operon promoter in the presence of the aromatic effector in the growth medium. However, the magnitude of the transcriptional response differs depending on the position of the methyl substituent on the aromatic ring. Experiments involving an elevated copy number of the dmp system demonstrate that growth on para-substituted methylphenols is limited by the level of the catabolic enzymes. An effector specificity mutant of DmpR, DmpR-E135K, that responded to the presence of 4-ethylphenol, a noneffector of the wild-type protein, was isolated by genetic selection. The single point mutation in DmpR-E135K, which results in a Glu-to-Lys change in residue 135, also results in a regulator with enhanced recognition of para-substituted methylphenols. The DmpR-E135K mutation, when introduced into the wild-type strain, confers enhanced utilization of the para-substituted methylphenols. These experiments demonstrate that the aromatic effector activation of wild-type DmpR by the para-substituted methylphenols is a major factor limiting the catabolism of these compounds. PMID- 8002580 TI - Multiple N-acyl-L-homoserine lactone autoinducers of luminescence in the marine symbiotic bacterium Vibrio fischeri. AB - In Vibrio fischeri, the synthesis of N-3-oxohexanoyl-L-homoserine lactone, the autoinducer for population density-responsive induction of the luminescence operon (the lux operon, luxICDABEG), is dependent on the autoinducer synthase gene luxI. Gene replacement mutants of V. fischeri defective in luxI, which had been expected to produce no autoinducer, nonetheless exhibited lux operon transcriptional activation. Mutants released into the medium a compound that, like N-3-oxohexanoyl-L-homoserine lactone, activated expression of the lux system in a dose-dependent manner and was both extractable with ethyl acetate and labile to base. The luxI-independent compound, also like N-3-oxohexanoyl-L-homoserine lactone, was produced by V. fischeri cells in a regulated, population density responsive manner and required the transcriptional activator LuxR for activity in the lux system. The luxI-independent compound was identified as N-octanoyl-L homoserine lactone by coelution with the synthetic compound in reversed-phase high-pressure liquid chromatography, by derivatization treatment with 2,4 dinitrophenylhydrazine, by mass spectrometry, and by nuclear magnetic resonance spectroscopy. A locus, ain, necessary and sufficient for Escherichia coli to synthesize N-octanoyl-L-homoserine lactone was cloned from the V. fischeri genome and found to be distinct from luxI by restriction mapping and Southern hybridization. N-Octanoyl-L-homoserine lactone and ain constitute a second, novel autoinduction system for population density-responsive signalling and regulation of lux gene expression, and possibly other genes, in V. fischeri. A third V. fischeri autoinducer, N-hexanoyl-L-homoserine lactone, dependent on luxI for its synthesis, was also identified. The presence of multiple chemically and genetically distinct but cross-acting autoinduction systems in V. fischeri indicates unexpected complexity for autoinduction as a regulatory mechanism in this bacterium. PMID- 8002581 TI - Identification and molecular genetic characterization of a sensor kinase responsible for coordinately regulating light harvesting and reaction center gene expression in response to anaerobiosis. AB - Our laboratory recently demonstrated that anaerobic induction of light harvesting and reaction center structural gene expression involved a trans-acting factor, RegA, which exhibits sequence similarity to the class of prokaryotic sensory transduction proteins known as response regulators (M. W. Sganga and C. E. Bauer, Cell 68:945-954, 1992). In this study, we performed a screen for additional genes involved in inducing anaerobic expression of light harvesting and reaction center structural genes. This search resulted in the isolation of four strains that were shown by complementation and marker rescue analysis to harbor mutations allelic to the originally described regA mutation and one strain with a mutation found to be linked but nonallelic to regA. Sequence analysis indicated that this additional gene, regB, codes for a polypeptide that exhibits sequence similarity to the prokaryotic family of histidine sensor kinases. Analysis of photosynthesis gene expression in regB mutants indicates that the disruption of regB results in a phenotype that is very similar to that described for regA mutants, namely, a failure to trans activate anaerobic expression of the puf, puh, and puc operons. In analogy to other prokaryotic sensory transduction systems, we propose that RegB functions as a membrane-spanning sensor kinase that controls the anaerobic phosphorylation state of RegA, which in turn controls the induction of light harvesting and reaction center structural genes. PMID- 8002582 TI - The biosynthetic gene cluster for coronamic acid, an ethylcyclopropyl amino acid, contains genes homologous to amino acid-activating enzymes and thioesterases. AB - Coronamic acid (CMA), an ethylcyclopropyl amino acid derived from isoleucine, functions as an intermediate in the biosynthesis of coronatine, a chlorosis inducing phytotoxin produced by Pseudomonas syringae pv. glycinea PG4180. The DNA required for CMA biosynthesis (6.9 kb) was sequenced, revealing three distinct open reading frames (ORFs) which share a common orientation for transcription. The deduced amino acid sequence of a 2.7-kb ORF designated cmaA contained six core sequences and two conserved motifs which are present in a variety of amino acid-activating enzymes, including nonribosomal peptide synthetases. Furthermore, CmaA contained a spatial arrangement of histidine, aspartate, and arginine residues which are conserved in the ferrous active site of some nonheme iron(II) enzymes which catalyze oxidative cyclizations. The deduced amino acid sequence of a 1.2-kb ORF designated cmaT was related to thioesterases of both procaryotic and eucaryotic origins. These data suggest that CMA assembly is similar to the thiotemplate mechanism of nonribosomal peptide synthesis. No significant similarities between a 0.9-kb ORF designated cmaU and other database entries were found. The start sites of two transcripts required for CMA biosynthesis were identified in the present study. pRG960sd, a vector containing a promoterless glucuronidase gene, was used to localize and study the promoter regions upstream of the two transcripts. Data obtained in the present study indicate that CMA biosynthesis is regulated at the transcriptional level by temperature. PMID- 8002583 TI - Multiple structural proteins are required for both transcriptional activation and negative autoregulation of Caulobacter crescentus flagellar genes. AB - The periodic and sequential expression of flagellar (fla) genes in the Caulobacter crescentus cell cycle depends on their organization into levels I to IV of a regulatory hierarchy in which genes at the top of the hierarchy are expressed early in the cell cycle and are required for the later expression of genes below them. In these studies, we have examined the regulatory role of level II fliF operon, which is located near the top of the hierarchy. The last gene in the fliF operon, flbD, encodes a transcriptional factor required for activation of sigma 54-dependent promoters at levels III and IV and negative autoregulation of the level II fliF promoter. We have physically mapped the fliF operon, identified four new genes in the transcription unit, and determined that the organization of these genes is 5'-fliF-fliG-flbE-fliN-flbD-3'. Three of the genes encode homologs of the MS ring protein (FliF) and two switch proteins (FliG and FliN) of enteric bacteria, and the fourth encodes a predicted protein (FlbE) without obvious similarities to known bacterial proteins. We have introduced nonpolar mutations in each of the open reading frames and shown that all of the newly identified genes (fliF, fliG, flbE, and fliN) are required in addition to flbD for activation of the sigma 54-dependent flgK and flbG promoters at level III. In contrast, fliF, fliG, and flbE, but not fliN, are required in addition to flbD for negative autoregulation of the level II fliF promoter. The simplest interpretation of these results is that the requirements of FlbD in transcriptional activation and repression are not identical, and we speculate that FlbD function is subject to dual or overlapping controls. We also discuss the requirement of multiple structural genes for regulation of levels II and III genes and suggest that fla gene expression in C. crescentus may be coupled to two checkpoints in flagellum assembly. PMID- 8002584 TI - Nucleotide sequence of the afimbrial-adhesin-encoding afa-3 gene cluster and its translocation via flanking IS1 insertion sequences. AB - The afa gene clusters encode afimbrial adhesins (AFAs) that are expressed by uropathogenic and diarrhea-associated Escherichia coli strains. The plasmid-borne afa-3 gene cluster is responsible for the biosynthesis of the AFA-III adhesin that belongs to the Dr family of hemagglutinins. Reported in this work is the nucleotide sequence of the 9.2-kb insert of the recombinant plasmid pILL61, which contains the afa-3 gene cluster cloned from a cystitis-associated E. coli strain (A30). The afa-3 gene cluster was shown to contain six open reading frames, designated afaA to afaF. It was organized in two divergent transcriptional units. Five of the six Afa products showed marked homologies with proteins encoded by previously described adhesion systems that allowed us to attribute to each of them a putative function in the biogenesis of the AFA-III adhesin. AfaE was identified as the structural adhesin product, whereas AfaB and AfaC were recognized as periplasmic chaperone and outer membrane anchor proteins, respectively. The AfaA and AfaF products were shown to be homologous to the PapI PapB transcriptional regulatory proteins. No function could be attributed to the AfaD product, the gene of which was previously shown to be dispensable for the synthesis of a functional adhesin. Upstream of the afa-3 gene cluster, a 1.2-kb region was found to be 96% identical to the RepFIB sequence of one of the enterotoxigenic E. coli plasmids (P307), suggesting a common ancestor plasmid. This region contains an integrase-like gene (int). Sequence analysis revealed the presence of an IS1 element between the int gene and the afa-3 gene cluster. Two other IS1 elements were detected and located in the vicinity of the afa-3 gene cluster by hybridization experiments. The afa-3 gene cluster was therefore found to be flanked by two IS1 elements in direct orientation and two in opposite orientations. The afa-3 gene cluster, flanked by two directly oriented IS1 elements, was shown to translocate from a recombinant plasmid to the E. coli chromosome. This translocation event occurred via IS1-specific recombination mediated by a recA-independent mechanism. PMID- 8002585 TI - Pleiotropic effects of a Yersinia pestis fur mutation. AB - A Yersinia pestis fur mutation was constructed by insertionally disrupting the fur open reading frame. Analysis of a Fur-regulated beta-galactosidase reporter gene revealed a loss of iron regulation as a result of the fur mutation. trans complementation with the cloned Y. pestis fur gene restored iron regulation. The expression of most iron-regulated proteins was also deregulated by this mutation; however, a number of iron-repressible and two iron-inducible polypeptides retained normal regulation. Mutations in fur or hmsH, a gene encoding an 86-kDa surface protein required for hemin storage, increased the sensitivity of Y. pestis cells to the bacteriocin pesticin. Interestingly, the Y. pestis fur mutant lost temperature control of hemin storage; however, expression of the HmsH polypeptide was not deregulated. When grown with excess iron, a Y. pestis fur mutant possessing the 102-kb pigmentation locus exhibited severe growth inhibition and a dramatic increase in the number of spontaneous nonpigmented chromosomal deletion mutants present at late log phase. These results suggest that the Fur protein of Y. pestis is an important global regulator and that a separate Fur-independent iron regulatory system may exist. PMID- 8002586 TI - Isolation and characterization of FliK-independent flagellation mutants from Salmonella typhimurium. AB - A flagellum of Salmonella typhimurium and Escherichia coli consists of three structural parts, a basal body, a hook, and a filament. Because the fliK mutants produce elongated hooks, called polyhooks, lacking filament portions, the fliK gene product has been believed to be involved in both the determination of hook length and the initiation of the filament assembly. In the present study, we isolated two mutants from S. typhimurium which can form flagella even in the absence of the fliK gene product. Flagellar structures were fractionated from these suppressor mutants and inspected by electron microscopy. The suppressor mutants produced polyhook-filament complexes in the fliK mutant background, while they formed flagellar structures apparently indistinguishable from those of the wild-type strain in the fliK+ background. Genetic and sequence analyses of the suppressor mutations revealed that they are located near the 3'-end of the flhB gene, which has been believed to be involved in the early process of the basal body assembly. On the basis of these results, we discuss the mechanism of suppression of the fliK defects by the flhB mutations and propose a hypothesis on the export switching machinery of the flagellar proteins. PMID- 8002587 TI - Molecular characterization of the Salmonella typhimurium flhB operon and its protein products. AB - The flhB and flhA genes constitute an operon called flhB operon on the Salmonella typhimurium chromosome. Their gene products are required for formation of the rod structure of flagellar apparatus. Furthermore, several lines of evidence suggest that they, together with FliI and FliH, may constitute the export apparatus of flagellin, the component protein of flagellar filament. In this study, we determined the nucleotide sequence of the entire flhB operon from S. typhimurium. It was shown that the flhB and flhA genes encode highly hydrophobic polypeptides with calculated molecular masses of 42,322 and 74,848 Da, respectively. Both proteins have several potential membrane-spanning segments, suggesting that they may be integral membrane proteins. The flhB operon was found to contain an additional open reading frame capable of encoding a polypeptide with a calculated molecular mass of 14,073 Da. We designated this open reading frame flhE. The N terminal 16 amino acids of FlhE displays a feature of a typical signal sequence. A maxicell labeling experiment enabled us to identify the precursor and mature forms of the flhE gene products. Insertion of a kanamycin-resistant gene cartridge into the chromosomal flhE gene did not affect the motility of the cells, indicating that the flhE gene is not essential for flagellar formation and function. We have overproduced and purified N-terminally truncated FlhB and FlhA proteins and raised antibodies against them. By use of these antibodies, localization of the FlhB and FlhA proteins was analyzed by Western blotting (immunoblotting) with the fractionated cell extracts. The results obtained indicated that both proteins are localized in the cytoplasmic membrane. PMID- 8002589 TI - Wild-type gas vesicle formation requires at least ten genes in the gvp gene cluster of Halobacterium halobium plasmid pNRC100. AB - To study the functions of the 13 gvp genes, gvpMLKJIHGFEDACN, on plasmid pNRC100 of Halobacterium halobium in gas vesicle formation, we carried out linker scanning mutagenesis of the gene cluster. We constructed a 24.5-kb Escherichia coli-H. halobium shuttle plasmid, pFL2, containing the gvp gene cluster and introduced a kanamycin resistance (kappa) cassette into each gene (except for gvpA). Transformation of H. halobium SD109, which had the entire gvp gene cluster deleted, with pFL2 and mutated pFL2 derivatives showed that while the unmutated gene cluster successfully programmed gas vesicle formation, derivatives with insertion of the kappa cassette in any of the gvp genes, except gvpM, did not lead to production of normal gas vesicles. Insertions in gvpL, -K, -J, -I, and -F resulted in a complete block in gas vesicle synthesis, while insertions in gvpH, G, -E, -D, -C, and -N resulted in greatly reduced gas vesicle synthesis. In most cases, the block in gas vesicle synthesis did not result from polar effects, since similar results were obtained for derivatives of the insertion mutants in which most of the internal portion of the kappa cassette was deleted and only small (15 to 54-bp) insertions remained. The only exceptions were for gvpH and gvpD, where deletion of the internal portion of the kappa insertions resulted in phenotypic reversion. Electron microscopic analysis of the kappa mutants revealed that interruptions of gvpC and gvpN result in the formation of smaller gas vesicle than in the wild type, while interruptions of gvpF, -G, -H, -J, -K, and L produce no discernible vesicle intermediates. These results indicate the gvpA, C, and -N, which have the rightward transcriptional orientation, encode structural proteins, with gvpC and gvpN necessary for late stages of vesicle formation, and gvpL, -K, -J, -I, -H, -G, and -F, which have the leftward transcriptional orientation encode proteins involved in early steps in the assembly of gas vesicles. PMID- 8002588 TI - Induction of the Escherichia coli aidB gene under oxygen-limiting conditions requires a functional rpoS (katF) gene. AB - The Escherichia coli aidB gene is regulated by two different mechanisms, an ada dependent pathway triggered by methyl damage to DNA and an ada-independent pathway triggered when cells are grown without aeration. In this report we describe our search for mutations affecting the ada-independent aidB induction pathway. The mutant strain identified carries two mutations affecting aidB expression. These mutations are named abrB (aidB regulator) and abrD. The abrB mutation is presently poorly characterized because of instability of the phenotype it imparts. The second mutation, abrD1, reduces the expression of aidB observed when aeration is ceased and oxygen becomes limiting. Genetic and phenotypic analysis of the abrD1 mutation demonstrates that it is an allele of rpoS. Thus, aidB is a member of the family of genes that are transcribed by a sigma S-directed RNA polymerase holoenzyme. Examination of aidB expression in an rpoS insertion mutant strain indicates that both rpoS13::Tn10 and abrD1 mutations reduce aidB expression under oxygen-limiting conditions that prevail in unaerated cultures, reduce aidB induction by acetate at a low pH, but have little or no effect on the ada-dependent alkylation induction of aidB. PMID- 8002590 TI - Importance of anaerobic superoxide dismutase synthesis in facilitating outgrowth of Escherichia coli upon entry into an aerobic habitat. AB - The manganese-containing isozyme of superoxide dismutase (MnSOD) is synthesized by Escherichia coli only during aerobiosis, in accordance with the fact that superoxide can be formed only in aerobic environments. In contrast, E. coli continues to synthesize the iron-containing isozyme (FeSOD) even in the absence of oxygen. A strain devoid of FeSOD exhibited no deficits during either anaerobic or continuously aerobic growth, but its growth lagged for 2 h during the transition from anaerobiosis to aerobiosis. Complementation of this defect with heterologous SODs established that anaerobic SOD synthesis per se is necessary to permit a smooth transition to aerobiosis. The growth deficit was eliminated by supplementation of the medium with branched-chain amino acids, indicating that the growth interruption was due to the established sensitivity of dihydroxyacid dehydratase to endogenous superoxide. Components of the anaerobic respiratory chain rapidly generated superoxide when exposed to oxygen in vitro, suggesting that this transition may be a period of acute oxidative stress. These results show that facultative bacteria must preemptively synthesize SOD during anaerobiosis in preparation for reaeration. The data suggest that evolution has chosen FeSOD for this function because of the relative availability of iron, in comparison to manganese, during anaerobiosis. PMID- 8002591 TI - The pca-pob supraoperonic cluster of Acinetobacter calcoaceticus contains quiA, the structural gene for quinate-shikimate dehydrogenase. AB - An 18-kbp Acinetobacter calcoaceticus chromosomal segment contains the pcaIJFBDKCHG operon, which is required for catabolism of protocatechuate, and pobSRA, genes associated with conversion of p-hydroxybenzoate to protocatechuate. The genetic function of the 6.5 kbp of DNA between pcaG and pobS was unknown. Deletions in this DNA were designed by removal of fragments between restriction sites, and the deletion mutations were introduced into A. calcoaceticus by natural transformation. The mutations prevented growth with either quinate or shikimate, growth substrates that depend upon qui gene function for their catabolism to protocatechuate. The location of quiA, a gene encoding quinate shikimate dehydrogenase, was indicated by its expression in one of the deletion mutants, and the position of the gene was confirmed by determination of its 2,427 bp nucleotide sequence. The deduced amino acid sequence of QuiA confirmed that it is a member of a family of membrane-associated, pyrrolo-quinoline quinone dependent dehydrogenases, as had been suggested by earlier biochemical investigations. Catabolism of quinate and skikimate is initiated by NAD(+) dependent dehydrogenases in other microorganisms, so it is evident that different gene pools were called upon to provide the ancestral enzyme for this metabolic step. PMID- 8002592 TI - Aerobic catabolism of phenylacetic acid in Pseudomonas putida U: biochemical characterization of a specific phenylacetic acid transport system and formal demonstration that phenylacetyl-coenzyme A is a catabolic intermediate. AB - The phenylacetic acid transport system (PATS) of Pseudomonas putida U was studied after this bacterium was cultured in a chemically defined medium containing phenylacetic acid (PA) as the sole carbon source. Kinetic measurement was carried out, in vivo, at 30 degrees C in 50 mM phosphate buffer (pH 7.0). Under these conditions, the uptake rate was linear for at least 3 min and the value of Km was 13 microM. The PATS is an active transport system that is strongly inhibited by 2,4-dinitrophenol, 4-nitrophenol (100%), KCN (97%), 2-nitrophenol (90%), or NaN3 (80%) added at a 1 mM final concentration (each). Glucose or D-lactate (10 mM each) increases the PATS in starved cells (140%), whereas arsenate (20 mM), NaF, or N,N'-dicyclohexylcarbodiimide (1 mM) did not cause any effect. Furthermore, the PATS is insensitive to osmotic shock. These data strongly suggest that the energy for the PATS is derived only from an electron transport system which causes an energy-rich membrane state. The thiol-containing compounds mercaptoethanol, glutathione, and dithiothreitol have no significant effect on the PATS, whereas thiol-modifying reagents such as N-ethylmaleimide and iodoacetate strongly inhibit uptake (100 and 93%, respectively). Molecular analogs of PA with a substitution (i) on the ring or (ii) on the acetyl moiety or those containing (iii) a different ring but keeping the acetyl moiety constant inhibit uptake to different extents. None of the compounds tested significantly increase the PA uptake rate except adipic acid, which greatly stimulates it (163%). The PATS is induced by PA and also, gratuitously, by some phenyl derivatives containing an even number of carbon atoms on the aliphatic moiety (4 phenyl-butyric, 6-phenylhexanoic, and 8-phenyloctanoic acids). However, similar compounds with an odd number of carbon atoms (benzoic, 3-phenylpropionic, 5 phenylvaleric, 7-phenylheptanoic, and 9-phenylnonanoic acids) as well as many other PA derivatives do not induce the system, suggesting that the true inducer molecule is phenylacetyl-coenzyme A (PA-CoA). Furthermore, after P. putida U is cultured in the same medium containing other carbon sources (glucose or octanoic, benzoic, or 4-hydroxyphenylacetic acid) in the place of PA, the PATS and PA-CoA are not detected; neither the PATS nor PA-CoA is found in cases in which mutants (PA- and PCL-) lacking the enzyme which catalyzed the initial step of the PA degradation (phenylacetyl-CoA ligase) are used. PA-CoA has been extracted from bacteria and identified as a true PA catabolite by high-performance liquid chromatography and also enzymatically with pure acyl-CoA:6-aminopenicillanic acid acyltransferase from Penicillium chrysogenum. PMID- 8002593 TI - Structural aspects and immunolocalization of the F420-reducing and non-F420 reducing hydrogenases from Methanobacterium thermoautotrophicum Marburg. AB - The F420-reducing hydrogenase and the non-F420-reducing hydrogenase (EC 1.12.99.1.) were isolated from a crude extract of Methanobacterium thermoautotrophicum Marburg. Electron microscopy of the negatively stained F420 reducing hydrogenase revealed that the enzyme is a complex with a diameter of 15.6 nm. It consists of two ring-like, stacked, parallel layers each composed of three major protein masses arranged in rotational symmetry. Each of these masses appeared to be subdivided into smaller protein masses. Electron microscopy of negatively stained samples taken from intermediate steps of the purification process revealed the presence of enzyme particles bound to inside-out membrane vesicles. Linker particles of 10 to 20 kDa which mediate the attachment of the hydrogenase to the cytoplasmic membrane were seen. Immunogold labelling confirmed that the F420-reducing hydrogenase is a membrane-bound enzyme. Electron microscopy of the negatively stained purified non-F420-reducing hydrogenase revealed that the enzyme is composed of three subunits exhibiting different diameters (5, 4, and 2 to 3 nm). According to immunogold labelling experiments, approximately 70% of the non-F420-reducing hydrogenase protein molecules were located at the cell periphery; the remaining 30% were cytoplasmic. No linker particles were observed for this enzyme. PMID- 8002594 TI - Sorbitol promotes growth of Zymomonas mobilis in environments with high concentrations of sugar: evidence for a physiological function of glucose fructose oxidoreductase in osmoprotection. AB - The gram-negative ethanologenic bacterium Zymomonas mobilis is able to grow in media containing high concentrations of glucose or other sugars. A novel compatible solute for bacteria, sorbitol, which enhances growth of Z. mobilis at glucose concentrations exceeding 0.83 M (15%), is described. Added sorbitol was accumulated intracellularly up to 1 M to counteract high external glucose concentrations (up to 1.66 M or 30%). Accumulation of sorbitol was triggered by a glucose upshift (e.g., from 0.33 to 1.27 M or 6 to 23%) and was prevented by the uncoupler CCCP (carbonyl cyanide m-chlorophenylhydrazone; 100 microM). The sorbitol transport system followed Michaelis-Menten kinetics, with an apparent Km of 34 mM and a Vmax of 11.2 nmol.min-1.mg-1 (dry mass). Sorbitol was produced by the cells themselves and was accumulated when growing on sucrose (1 M or 36%) by the action of the periplasmic enzyme glucose-fructose oxidoreductase, which converts glucose and fructose to gluconolactone and sorbitol. Thus, Z. mobilis can form and accumulate the compatible solute sorbitol from a natural carbon source, sucrose, in order to overcome osmotic stress in high-sugar media. No other major compatible solute (betaine, proline, glutamate, or trehalose) was detected. PMID- 8002595 TI - Multiple chromosomes in bacteria: structure and function of chromosome II of Rhodobacter sphaeroides 2.4.1T. AB - Although multiple chromosomes occur in bacteria, much remains to be learned about their structural and functional interrelationships. To study the structure function relationships of chromosomes I and II of the facultative photosynthetic bacterium Rhodobacter sphaeroides 2.4.1T, auxotrophic mutants were isolated. Five strains having transposon insertions in chromosome II showed requirements for p aminobenzoic acid (pABA)-dihydroxybenzoic acid (dHBA), serine, thymine, uracil, or histidine. The His, Thy, and pABA-dHBA mutants reverted to prototrophy at low frequency and concordantly lost their transposon insertions from the genome. The Ser, Ura, and pABA-dHBA mutants were complemented by cosmids that carried the region of chromosome II where the transposon insertions were located. The cosmids used for complementation analysis were selected, on the basis of map position, from a set of overlapping clones that had been ordered by a combination of hybridization and restriction endonuclease mapping. These experiments provide the basis for detailed studies of the structure, function, and interaction between each chromosome, and they demonstrate at this early stage of investigation that no fundamental differences exist between each chromosome. PMID- 8002597 TI - Conservation of chromosomal arrangement among three strains of the genetically unstable archaeon Halobacterium salinarium. AB - Phenotypic variants of Halobacterium salinarium NRC-1 arise at a frequency of 10( 2). These result from transpositions of halobacterial insertion sequences and rearrangements mediated by halobacterial insertion sequences. We have tested the hypothesis that such mutations are confined to only a portion of the genome by comparing the chromosomal restriction map of H. salinarium NRC-1 and that of the derivative S9, which was made in 1969. The two chromosomes were mapped by using two-dimensional pulsed-field gel electrophoresis and the restriction enzymes AflII, AseI, and DraI. A comparison of the two deduced maps showed a domain of about 210 kbp to be subject to many rearrangements, including an inversion in S9 relative to NRC-1. However, the rest of the chromosome was conserved among NRC-1, S9, and an independent Halobacterium isolate, GRB, previously mapped by St. Jean et al. (A. St. Jean, B. A. Trieselmann, and R. L. Charlebois, Nucleic Acids Res. 22:1476-1483, 1994). This concurs with data from eubacteria suggesting strong selective forces maintaining gene order even in the face of rearrangement events occurring at a high frequency. PMID- 8002596 TI - Phylogenetic depth of S10 and spc operons: cloning and sequencing of a ribosomal protein gene cluster from the extremely thermophilic bacterium Thermotoga maritima. AB - A segment of Thermotoga maritima DNA spanning 6,613 bp downstream from the gene tuf for elongation factor Tu was sequenced by use of a chromosome walking strategy. The sequenced region comprised a string of 14 tightly linked open reading frames (ORFs) starting 50 bp downstream from tuf. The first 11 ORFs were identified as homologs of ribosomal protein genes rps10, rpl3, rpl4, rpl23, rpl2, rps19, rpl22, rps3, rpl16, rpl29, and rps17 (which in Escherichia coli constitute the S10 operon, in that order); the last three ORFs were homologous to genes rpl14, rpl24, and rpl5 (which in E. coli constitute the three promoter-proximal genes of the spectinomycin operon). The 14-gene string was preceded by putative 35 and -10 promoter sequences situated 5' to gene rps10, within the 50-bp spacing between genes tuf and rps10; the same region exhibited a potential transcription termination signal for the upstream gene cluster (having tuf as the last gene) but displayed also the potential for formation of a hairpin loop hindering the terminator; this suggests that transcription of rps10 and downstream genes may start farther upstream. The similar organization of the sequenced rp genes in the deepest-branching bacterial phyla (T. maritima) and among Archaea has been interpreted as indicating that the S10-spc gene arrangement existed in the (last) common ancestor. The phylogenetic depth of the Thermotoga lineage was probed by use of r proteins as marker molecules: in all except one case (S3), Proteobacteria or the gram-positive bacteria, and not the genus Thermotoga, were the deepest-branching lineage; in only two cases, however, was the inferred branching order substantiated by bootstrap analysis. PMID- 8002598 TI - Genetic and biochemical analyses of the biosynthesis of the yellow carotenoid 4,4'-diaponeurosporene of Staphylococcus aureus. AB - The major pigment produced by Staphylococcus aureus Newman is the deep-yellow carotenoid 4,4'-diaponeurosporene; after prolonged cultivation, this pigment is in part converted to the orange end product staphyloxanthin. From this strain a 3.5-kb DNA fragment was identified which after being cloned into Escherichia coli and Staphylococcus carnosus conferred the ability to produce 4,4' diaponeurosporene. DNA sequencing of this fragment revealed two open reading frames (ORFs) which are very likely cotranscribed. ORF1 encodes a 254-amino-acid hydrophobic protein, CrtM (M(r), 30,121). The deduced sequence of CrtM exhibits in three domains similarities to the sequences of Saccharomyces cerevisiae and human squalene synthases and phytoene synthases of various bacteria. ORF2 encodes a 448-amino-acid hydrophobic protein, CrtN, with an M(r) of 50,853 whose deduced sequence is similar to those of phytoene desaturases of other bacteria. At the N terminus of CrtN a classical FAD-, NAD(P)-binding domain is found. Spectrophotometry and gas chromatography-mass spectrometry analyses of the carotenoid production of E. coli and S. carnosus clones containing either ORF1 or both ORFs together suggest that ORF1 and ORF2 represent the dehydrosqualene synthase gene (crtM) and the dehydrosqualene desaturase gene (crtN), respectively. The results furthermore suggest that the biosynthesis of 4,4' diaponeurosporene starts with the condensation of two molecules of farnesyl diphosphate by dehydrosqualene synthase (CrtM); it is shown that the reaction product of this enzyme is dehydrosqualene and not squalene. Dehydrosqualene (4,4' diapophytoene) is successively dehydrogenated by a desaturase (CrtN) to form the yellow main intermediate 4,4'-diaponeurosporene. PMID- 8002599 TI - Activity of the Escherichia coli mutT mutator allele in an anaerobic environment. AB - Mutation frequencies for an Escherichia coli mutT strain were measured in both aerobic and anaerobic environments. When cells were grown in a rich medium (L broth), mutation frequencies were similar in both aerobic and anaerobic conditions. In contrast, when grown in a minimal medium, mutT anaerobic mutation frequencies were reduced dramatically compared with aerobic values, which were similar to L broth frequencies. L broth mutT cultures treated with a commercial enzyme complex that reduces free oxygen in the medium also showed strongly reduced anaerobic mutation frequencies. These results indicate that the biological role of the MutT protein is to prevent oxidative damage from becoming mutagenic. PMID- 8002600 TI - Molecular cloning and expression of an isomalto-dextranase gene from Arthrobacter globiformis T6. AB - The gene encoding an extracellular isomalto-dextranase, designated imd, was isolated from the chromosomal DNA of Arthrobacter globiformis T6 and cloned and expressed in Escherichia coli. A single open reading frame consisting of 1,926 base pairs that encoded a polypeptide composed of a signal peptide of 39 amino acids and a mature protein of 602 amino acids (M(r), 65,900) was found. The primary structure had no significant homology with the structures of any other reported carbohydrases, including two other dextranases. Transformed E. coli cells carrying the 2.3-kb fragment overproduced isomalto-dextranase into the periplasmic space under control of the promoter of the imd gene itself. PMID- 8002602 TI - Serine residue 45 of nodulation protein NodF from Rhizobium leguminosarum bv. viciae is essential for its biological function. AB - A system for testing the role of the Rhizobium nodF gene in the production of host-specific lipochitin oligosaccharides and in nodulation was developed. We show that a mutant nodF gene, in which the codon for serine residue 45 was changed to that for threonine, still expresses NodF, which, however, is no longer functional. PMID- 8002601 TI - The incN plasmid replicon: two pathways of DNA polymerase I-independent replication. AB - The 2,053-bp broad-host-range incompatibility group N replicon of plasmid pCU1 has two components: a region of 1,200 bp that is sufficient for its replication in Escherichia coli PolA+ and PolA- hosts and a regulatory region called the group I iteron region that contains 13 39-bp iterons. Within the 1,200-bp region, there are three replication origins, two of which, called oriB and oriS, function in PolA+ and PolA- hosts and a third, called oriV, which functions only in PolA+ hosts. The region also specifies a protein called RepA. We now show that both oriB and oriS can function in a delta polA strain but that in such a strain, only oriB has an absolute requirement for RepA. oriS can function without RepA and polymerase I provided that the iteron region is deleted and that in this circumstance, it is the only origin, the usage of which is detected. The requirements for oriB usage can thus be distinguished from those for oriS usage. The oriB region can be recovered as a plasmid only if RepA is provided in trans. These complex features of this replicon are also shown to be shared by the IncN replicons of other antibiotic resistance plasmids. Functionally distinguishable origins in a small replicon may be a way of endowing such a replicon with a broad host range. PMID- 8002603 TI - A spontaneous point mutation in the single 23S rRNA gene of the thermophilic arachaeon Sulfolobus acidocaldarius confers multiple drug resistance. AB - Development of transformable vectors for thermophilic archaea requires the characterization of appropriate selectable marker genes. Many antibiotic inhibitors of protein biosynthesis are known to bind to rRNA; therefore, we screened 14 for their capacity to inhibit growth of the thermophilic archaeon Sulfolobus acidocaldarius. Carbomycin, celesticetin, chloramphenicol, puromycin, sparsomycin, tetracycline, and thiostrepton all inhibited growth by different degrees. Spontaneous drug-resistant mutants were isolated from plates containing celesticetin or chloramphenicol. Six mutants from each plate exhibited a C-2585 to-U transition in the peptidyl transferase loop of 23S rRNA (corresponding to C 2452 in Escherichia coli 23S rRNA). The single-site mutation also conferred resistance to carbomycin. The mutated 23S rRNA gene provides a potentially useful and dominant marker for a thermophilic archael vector. PMID- 8002604 TI - Analysis of the genetic requirements for inducible multiple-antibiotic resistance associated with the mar locus in Escherichia coli. AB - A series of novel genetic constructs derived from the marRAB operon was used to determine the role of this gene cluster in salicylate-inducible multiple antibiotic resistance in Escherichia coli. Our findings indicate that regulated antibiotic resistance associated with this locus requires only the products of marR and marA, without any neighboring genes. PMID- 8002605 TI - Organization and evolution of naphthalene catabolic pathways: sequence of the DNA encoding 2-hydroxychromene-2-carboxylate isomerase and trans-o hydroxybenzylidenepyruvate hydratase-aldolase from the NAH7 plasmid. AB - The sequence of a 2,437-bp DNA segment from the naphthalene upper catabolic pathway operon of plasmid NAH7 was determined. This segment contains three large open reading frames designated nahQ', nahE, and nahD. The first of these is the 3' end of an open reading frame that has no known function, the second (993 bp) encodes trans-o-hydroxybenzylidenepyruvate hydratase-aldolase (deduced molecular weight, 36,640), and the third (609 bp) encodes 2-hydroxychromene-2-carboxylate isomerase (deduced molecular weight, 23,031). This DNA has a high degree of sequence homology (greater than 91% for the first 2161 bp) with a DNA segment from the dox (dibenzothiophene oxidation) operon of Pseudomonas sp. strain C18, which encodes a pathway analogous to that encoded by NAH7. However, 84 bp downstream from nahD, the last gene in the nah operon, this homology ends. This 84-bp sequence at the downstream end of nah and dox homology has 76% homology to a sequence that occurs just upstream of the nah promoter in NAH7. These directly repeated 84-bp sequences thus encompass the upper-pathway nah operon and constitute the ends of a highly conserved region. PMID- 8002606 TI - Isolation of a Bacillus subtilis spoIIGA allele that suppresses processing negative mutations in the Pro-sigma E gene (sigE). AB - sigma E, a sporulation-essential sigma factor of Bacillus subtilis, is formed by a developmentally regulated proteolysis which removes 27 to 29 amino acids from the amino terminus of an inactive precursor protein (Pro-sigma E). A mutation which facilitates the conversion of inefficiently processed Pro-sigma E variants into mature sigma E was identified and mapped to spoIIGA. The isolation of such a mutation argues that SpoIIGA is directly involved in the Pro-sigma E processing reaction. PMID- 8002607 TI - Lipoic acid metabolism in Escherichia coli: the lplA and lipB genes define redundant pathways for ligation of lipoyl groups to apoprotein. AB - Lipoic acid is a covalently bound disulfide-containing cofactor required for function of the pyruvate dehydrogenase, alpha-ketoglutarate dehydrogenase, and glycine cleavage enzyme complexes of Escherichia coli. Recently we described the isolation of the lplA locus, the first gene known to encode a lipoyl-protein ligase for the attachment of lipoyl groups to lipoate-dependent apoenzymes (T. W. Morris, K. E. Reed, and J. E. Cronan, Jr., J. Biol. Chem. 269:16091-16100, 1994). Here, we report an unexpected redundancy between the functions of lplA and lipB, a gene previously identified as a putative lipoate biosynthetic locus. First, analysis of lplA null mutants revealed the existence of a second lipoyl ligase enzyme. We found that lplA null mutants displayed no growth defects unless combined with lipA (lipoate synthesis) or lipB mutations and that overexpression of wild-type LplA suppressed lipB null mutations. Assays of growth, transport, lipoyl-protein content, and apoprotein modification demonstrated that lplA encoded a ligase for the incorporation of exogenously supplied lipoate, whereas lipB was required for function of the second lipoyl ligase, which utilizes lipoyl groups generated via endogenous (lipA-mediated) biosynthesis. The lipB-dependent ligase was further shown to cause the accumulation of aberrantly modified octanoyl-proteins in lipoate-deficient cells. Lipoate uptake assays of strains that overproduced lipoate-accepting apoproteins also demonstrated coupling between transport and the subsequent ligation of lipoate to apoprotein by the LplA enzyme. Although mutations in two genes (fadD and fadL) involved in fatty acid failed to affect lipoate utilization, disruption of the smp gene severely decreased lipoate utilization. DNA sequencing of the previously identified slr1 selenolipoate resistance mutation (K. E. Reed, T. W. Morris, and J. E. Cronan, Jr., Proc. Natl. Acad. Sci. USA 91:3720-3724, 1994) showed this mutation (now called lplA1) to be a G76S substitution in the LplA ligase. When compared with the wild-type allele, the cloned lplA1 allele conferred a threefold increase in the ability to discriminate against the selenium-containing analog. These results support a two-pathway/two-ligase model of lipoate metabolism in E. coli. PMID- 8002609 TI - The Bacillus subtilis rsbU gene product is necessary for RsbX-dependent regulation of sigma B. AB - sigma B is a secondary sigma factor of Bacillus subtilis. sigma B-dependent transcription is induced when B. subtilis enters the stationary phase of growth or is exposed to any of a number of different environmental stresses. Three genes (rsbV, rsbW, and rsbX), which are cotranscribed with the sigma B structural gene (sigB), encode regulators of sigma B-dependent gene expression. RsbW and RsbV have been shown to control sigma B activity, functioning as an inhibitory sigma B binding protein and its antagonist, respectively. Using the SPAC promoter (PSPAC) to control the expression of the sigB operon, a ctc::lacZ reporter system to monitor sigma B activity, and monoclonal antibodies to determine the levels of sigB operon products, we have now obtained evidence that RsbX is an indirect regulator of sigma B activity. Genetic data and in vivo measurements argue that RsbX negatively regulates an extension of the RsbV-RsbW pathway that requires the product of an additional regulatory gene (rsbU) which lies immediately upstream of the sigB operon. The results are consistent with RsbU, or a process dependent on RsbU, being able to facilitate the RsbV-dependent release of sigma B from RsbW but normally prevented from doing this by RsbX. PMID- 8002608 TI - The leucine-responsive regulatory protein of Escherichia coli negatively regulates transcription of ompC and micF and positively regulates translation of ompF. AB - The two major porins of Escherichia coli K-12 strains, OmpC and OmpF, are inversely regulated with respect to one another. The expression of OmpC and OmpF has been shown to be influenced by the leucine-responsive regulatory protein (Lrp): two-dimensional gel electrophoresis of proteins from strains with and strains without a functional Lrp protein revealed that OmpC expression is increased in an lrp strain, while OmpF expression is decreased. In agreement with these findings, we now present evidence that transcriptional (operon) fusions of lacZ+ to ompC and micF are negatively regulated by Lrp. Lrp binds specifically to the intergenic region between micF and ompC, as indicated by mobility shift assays and by DNase I footprinting. The expression of an ompF'-lacZ+ gene (translational) fusion is increased 3.7-fold in an lrp+ background compared with an lrp background, but expression of an ompF-lacZ+ operon fusion is not. Studies of in vivo expression of the outer membrane porins during growth on glucose minimal medium showed that the OmpF/OmpC ratio is higher in lrp+ strains than it is in isogenic lrp strains. The effect of Lrp was not seen in a strain containing a deletion of micF. Our studies suggest that the positive effect of Lrp on OmpF expression stems from a negative effect of Lrp on the expression of micF, an antisense RNA that inhibits ompF translation. PMID- 8002610 TI - Four additional genes in the sigB operon of Bacillus subtilis that control activity of the general stress factor sigma B in response to environmental signals. AB - sigma B of the gram-positive bacterium Bacillus subtilis is an alternative transcription factor activated by a variety of environmental stresses, including the stress imposed upon entry into the stationary growth phase. Previous reports have shown that this stationary-phase activation is enhanced when cells are grown in rich medium containing glucose and glutamine. The sigma B structural gene, sigB, lies in an operon with three other genes whose products have been shown to control sigma B activity in response to environmental stress. However, none of these is sufficient to explain the enhanced stationary-phase activation of sigma B in response to glucose. We show here that the four genes previously identified in the sigB operon constitute the downstream half of an eight-gene operon. The complete sigB operon is preceded by a sigma A-like promoter (PA) and has the order PA-orfR-orfS-orfT-orfU-PB-rsbV-rsbW-sig B-rsbX, where rsb stands for regulator of sigma-B and the previously identified sigma B-dependent promoter (PB) is an internal promoter preceding the downstream four-gene cluster. Although the genes downstream of PB were also transcribed by polymerase activity originating at PA, this transcription into the downstream cluster was not essential for normal induction of a sigma B-dependent ctc-lacZ fusion. However, deletion of all four upstream open reading frames was found to interfere with induction of the ctc-lacZ fusion in response to glucose. Additional deletion analysis and complementation studies showed that orfU was required for full glucose induction of sigma B-dependent genes. orfU encodes a trans-acting, positive factor with significant sequence identity to the RsbX negative regulator of sigma B. On the basis of these results, we rename orfU as rsbU to symbolize the regulatory role of its product. PMID- 8002611 TI - Two different Escherichia coli proP promoters respond to osmotic and growth phase signals. AB - proP of Escherichia coli encodes an active transport system for proline and glycine betaine which is activated by both hyperosmolarity and amino acid-limited growth. proP DNA sequences far upstream from the translational start site are strongly homologous to the promoter of proU, an operon that specifies another osmoregulated glycine betaine transport system. Mutation and deletion analysis of proP and primer extension experiments established that this promoter, P1, was responsible for proP's strong expression in minimal medium and its response to osmotic signals. When cells were grown in complex medium, expression from a proP lacZ fusion was induced three- to fourfold as growth slowed and cells entered stationary phase. Stationary-phase induction was dependent on rpoS, which encodes a stationary-phase sigma factor. Deletion of 158 bp of the untranslated leader sequence between P1 and the proP structural gene abolished rpoS-dependent stationary-phase regulation. Transcription initiation detected by primer extension within this region was absent in an rpoS mutant. proP is therefore a member of the growing class of sigma S-dependent genes which respond to both stationary-phase and hyperosmolarity signals. PMID- 8002612 TI - Purification and characterization of a novel extracellular Streptomyces lividans 66 enzyme inactivating fusidic acid. AB - The wild-type strain Streptomyces lividans 66 is resistant against the steroid like antibiotic fusidic acid. Comparative studies of the wild-type strain and a fusidic acid-sensitive mutant allowed the identification of an extracellular enzyme which inactivates fusidic acid. With the help of a combination of ultrafiltration and chromatographies with Phenyl-Sepharose and an anion exchanger, the enzyme was highly purified. Its apparent molecular mass is 48 kDa, its optimal activity ranges between 45 and 55 degrees C, and its optimal pH is 6.0 to 9.0. It is stimulated by neither monovalent nor divalent ions. The enzyme acts as a specific esterase which removes the acetyl group at C-16 from fusidic acid. The resulting intermediate is unstable, and spontaneous lactonization between C-21 and C-16 occurs rapidly. PMID- 8002613 TI - The pcsA gene is identical to dinD in Escherichia coli. AB - The pcsA68 mutant of Escherichia coli is a cold-sensitive mutant which forms long filaments with a large nucleoid in the central region at 20 degrees C. We here show that (i) the coding region for the pcsA gene is identical with orfY located upstream of pyrE and can be deleted without loss of viability; (ii) pcsA is also identical to dinD, a DNA damage-inducible gene, whose expression is regulated by the LexA-RecA system; (iii) the cold-sensitive phenotype of the pcsA68 mutation is suppressed by delta recA or lexA1 (Ind-) mutation, but not by sulA inactivation; (iv) overproduction of PcsA68 leads to inhibition of cell growth in recA+ and delta recA strains at 20 and 37 degrees C, but PcsA+ does not show such an effect at any temperature; (v) SOS response is induced in the pcsA68 mutant cells at 20 degrees C. We discuss the possible function of the pcsA gene, comparing it with the sulA or the dif-xerCD function. We also describe a new method for gene disruption with positive and negative selection. PMID- 8002614 TI - Isolation and characterization of kinC, a gene that encodes a sensor kinase homologous to the sporulation sensor kinases KinA and KinB in Bacillus subtilis. AB - Phosphorylation of the transcription factor encoded by spo0A is required for the initiation of sporulation in Bacillus subtilis. Production and accumulation of Spo0A-P is controlled by histidine protein kinases and the spo0 gene products. To identify additional genes that might be involved in the initiation of sporulation and production of Spo0A-P, we isolated genes which when present on a multicopy plasmid could suppress the sporulation defect of a spo0K mutant. kinC was one gene isolated in this way. A multicopy plasmid containing kinC completely or partially suppressed the sporulation defect caused by mutations in spo0K, kinA, spo0F, and spo0B, indicating that at least when overexpressed, KinC is capable of stimulating phosphorylation of Spo0A independently of the normal phosphorylation pathway. The predicted product of kinC is 428 amino acids long and is most similar to KinA and KinB, the histidine protein kinases involved in the initiation of sporulation. In otherwise wild-type strains, kinC null mutations caused little or no defect in sporulation under the conditions tested. However, in the absence of a functional phosphorelay (spo0F or spo0B), KinC appears to be the kinase responsible for phosphorylation of the sof-1 and rvtA11 forms of Spo0A. PMID- 8002615 TI - Analysis of a suppressor mutation ssb (kinC) of sur0B20 (spo0A) mutation in Bacillus subtilis reveals that kinC encodes a histidine protein kinase. AB - sur0B20 is a mutation that suppresses the effects of spo0B delta B or spo0F221 mutations in Bacillus subtilis, sur0B20 is an allele of the spo0A gene (Glu-14 to Val-14 conversion) and restores the sporulation of spo0B or spo0F mutants to the wild-type level. Here, we report the isolation of suppressor mutations of sur0B20 (ssb). One of these mutations, ssb-12, severely impairs the suppressor activity of sur0B20. A 2.5-kbp MboI fragment which complements the ssb-12 mutation was cloned by the prophage transformation method using phi CM as a vector. Nucleotide sequencing of the fragment revealed two open reading frames (orf1 and orf2). Gene disruption and complementation experiments showed that orf2 is the ssb gene. ssb was shown to encode a protein with a molecular weight of 48,846 (428 amino acid residues) showing strong similarity to transmitter kinases, especially KinA, of two-component regulatory systems. Therefore, ssb was renamed kinC. Deletion of kinC had no observable effect on sporulation. kinC transcription was induced at the onset of sporulation, probably from a sigma A-dependent promoter, and its expression was shut off at T3. DNase I protection experiments showed that the Spo0A protein binds to two adjoining sites in the kinC promoter region with different affinities. These results suggest that kinC expression might be regulated by Spo0A. PMID- 8002616 TI - Cloning and sequencing of a cluster of genes encoding branched-chain alpha-keto acid dehydrogenase from Streptomyces avermitilis and the production of a functional E1 [alpha beta] component in Escherichia coli. AB - A cluster of genes encoding the E1 alpha, E1 beta, and E2 subunits of branched chain alpha-keto acid dehydrogenase (BCDH) of Streptomyces avermitilis has been cloned and sequenced. Open reading frame 1 (ORF1) (E1 alpha), 1,146 nucleotides long, would encode a polypeptide of 40,969 Da (381 amino acids). ORF2 (E1 beta), 1,005 nucleotides long, would encode a polypeptide of 35,577 Da (334 amino acids). The intergenic distance between ORF1 and ORF2 is 73 bp. The putative ATG start codon of the incomplete ORF3 (E2) overlaps the stop codon of ORF2. Computer aided searches showed that the deduced products of ORF1 and ORF2 resembled the corresponding E1 subunit (alpha or beta) of several prokaryotic and eukaryotic BCDH complexes. When these ORFs were overexpressed in Escherichia coli, proteins of about 41 and 34 kDa, which are the approximate masses of the predicted S. avermitilis ORF1 and ORF2 products, respectively, were detected. In addition, specific E1 [alpha beta] BCDH activity was detected in E. coli cells carrying the S. avermitilis ORF1 (E1 alpha) and ORF2 (E1 beta) coexpressed under the control of the T7 promoter. PMID- 8002617 TI - In vitro studies of the domains of the nitrogen fixation regulatory protein NIFA. AB - The prokaryotic enhancer-binding protein NIFA is a multidomain transcriptional activator that catalyzes the formation of open complexes at nitrogen fixation (nif) promoters by a specialized form of RNA polymerase containing sigma 54. The NIFA protein from Klebsiella pneumoniae consists of three domains: the N-terminal domain of unknown function; the central catalytic domain, which is sufficient for transcriptional activation; and the C-terminal DNA-binding domain. Purified fusion proteins between maltose-binding protein (MBP) and NIFA deleted of its N terminal domain (MBP-delta N-NIFA) or its C-terminal domain (MBP-NIFA-delta C) activated transcription from the K. pneumoniae nifH promoter both in vitro and in vivo. We previously showed that the same was true for a fusion between MBP and the central domain of NIFA. These results indicate that NIFA is sufficiently modular for all fusions carrying its catalytic domain to be active. Unexpectedly, however, simple predictions regarding the location of determinants of the heat lability and insolubility of NIFA, which were based on previous studies of its isolated central and C-terminal domains, were not borne out. Contrary to a previous report from this laboratory, we found that the in vitro start site of transcription for the K. pneumoniae nifH operon could be either of two adjacent G residues, as others had reported in vivo. This was true independent of the activator, i.e., with MBP-NIFA and MBP-delta N-NIFA and with the homologous activator NTRC. When open complexes were formed with GTP as the activating nucleotide, the upstream G residue was probably as a consequence of initiation of transcription. PMID- 8002618 TI - Dihydroxylation and dechlorination of chlorinated biphenyls by purified biphenyl 2,3-dioxygenase from Pseudomonas sp. strain LB400. AB - Oxidation of biphenyl and nine chlorinated biphenyls (CBs) by the biphenyl 2,3 dioxygenase from Pseudomonas sp. strain LB400 was examined. The purified terminal oxygenase required the addition of partially purified electron transport components, NAD(P)H, and ferrous iron to oxidize biphenyl and CBs. cis-Biphenyl 2,3-dihydrodiol was produced with biphenyl as the substrate. Dihydrodiols were produced from all CBs, and more than one compound was produced with most substrates. Catechols were produced when the dioxygenase-catalyzed reaction occurred at the 2,3 position of a 2-chlorophenyl ring, resulting in dechlorination of the substrate. Oxidation at the 3,4 position of a 2,5 dichlorophenyl ring produced a 3,4-dihydrodiol. Compounds resulting from both types of reaction were produced during oxidation of 2,5,2'-trichlorobiphenyl. The broad substrate specificity and the ability to oxidize at different ring positions suggest that the biphenyl 2,3-dioxygenase is responsible for the wide range of CBs oxidized by Pseudomonas sp. strain LB400. PMID- 8002619 TI - Inositol monophosphatase activity from the Escherichia coli suhB gene product. AB - The suhB gene is located at 55 min on the Escherichia coli chromosome and encodes a protein of 268 amino acids. Mutant alleles of suhB have been isolated as extragenic suppressors for the protein secretion mutation (secY24), the heat shock response mutation (rpoH15), and the DNA synthesis mutation (dnaB121) (K. Shiba, K. Ito, and T. Yura, J. Bacteriol. 160:696-701, 1984; R. Yano, H. Nagai, K. Shiba, and T. Yura, J. Bacteriol. 172:2124-2130, 1990; S. Chang, D. Ng, L. Baird, and C. Georgopoulos, J. Biol. Chem. 266:3654-3660, 1991). These mutant alleles of suhB cause cold-sensitive cell growth, indicating that the suhB gene is essential at low temperatures. Little work has been done, however, to elucidate the role of the product of suhB in a normal cell and the suppression mechanisms of the suhB mutations in the aforementioned mutants. The sequence similarity shared between the suhB gene product and mammalian inositol monophosphatase has prompted us to test the inositol monophosphatase activity of the suhB gene product. We report here that the purified SuhB protein showed inositol monophosphatase activity. The kinetic parameters of SuhB inositol monophosphatase (Km = 0.071 mM; Vmax = 12.3 mumol/min per mg) are similar to those of mammalian inositol monophosphatase. The ssyA3 and suhB2 mutations, which were isolated as extragenic suppressors for secY24 and rpoH15, respectively, had a DNA insertion at the 5' proximal region of the suhB gene, and the amount of SuhB protein within mutant cells decreased. The possible role of suhB in E. coli is discussed. PMID- 8002621 TI - [Effectiveness of thrice-weekly injection of romurutide for prophylaxis of leukocytopenia during radiation therapy]. AB - The effectiveness of thrice-weekly injection of Romurutide for leukocytopenia due to radiation therapy was analyzed. Twenty-two patients were randomly divided into two groups. Ten of group A cases were injected 3 times per week 10 times (3 weeks) and 12 of group B cases were injected 5 times per week 10 times (2 weeks). White blood cell counts and neutrophil numbers in group A were almost the same as in group B at day-3 and day-8, and those in group A were more than in group B at day-15 and day-22, although there were no statistical significances. Lymphocyte percentages, monocyte percentages and platelet cell counts between groups showed no differences. Injections were stopped in 3 cases due to fever (2 in group A, 1 in group B). The effects were recognized in nineteen cases (excluding above 3 cases). The effect of this thrice-weekly injection method during the injection period was the same or more than with 5 injections/week, and the period of the former was 50% longer. The 3 weekly injection method is more effective for prophylaxis of leukocytopenia. PMID- 8002622 TI - [A study of intra-arterial infusion with carboplatin (CBDCA) for 2 patients with maxillary gingival cancer]. AB - In 2 cases of squamous cell carcinoma of maxillary gingiva, carboplatin (CBDCA) was administered by continuous infusion for 5 days, and the clinical outcome and platinum concentrations in the peripheral blood, urine and tissue were investigated. Clinical effects were PR in one of the 2 cases and CR in the other. Platinum concentrations were as high as 3.17 and 13.90 micrograms/g in the tissue, but low in peripheral blood, not exceeding 0.61 and 0.62 micrograms/ml, respectively. These findings suggested that the present method secures the transport of the agent to a local site, with possible reduction of side effects. PMID- 8002620 TI - Transcriptional analysis of pqqD and study of the regulation of pyrroloquinoline quinone biosynthesis in Methylobacterium extorquens AM1. AB - Methanol dehydrogenase, the enzyme that oxidizes methanol to formaldehyde in gram negative methylotrophs, contains the prosthetic group pyrroloquinoline quinone (PQQ). To begin to analyze how the synthesis of PQQ is coordinated with the production of other methanol dehydrogenase components, the transcription of one of the key PQQ synthesis genes has been studied. This gene (pqqD) encodes a 29 amino-acid peptide that is thought to be the precursor for PQQ biosynthesis. A unique transcription start site was mapped to a guanidine nucleotide 95 bp upstream of the pqqD initiator codon. RNA blot analysis identified two transcripts, a major one of 240 bases encoding pqqD and a minor one of 1,300 bases encoding pqqD and the gene immediately downstream, pqqG. Both transcripts are present at similar levels in cells grown on methanol and on succinate, but the levels of PQQ are about fivefold higher in cells grown on methanol than in cells grown on succinate. These results suggest that PQQ production is regulated at a level different from the transcription of pqqD. The genes mxbM, mxbD, mxcQ, mxcE, and mxaB are required for transcription of the genes encoding the methanol dehydrogenase subunits and were assessed for their role in PQQ production. PQQ levels were measured in mutants defective in each of these regulatory genes and compared with levels of pqqD transcription, measured with a transcriptional fusion between the pqqD promoter and xylE. The results showed that only a subset of these regulatory genes (mxbM, mxbD, and mxaB) is required for transcription of pqqD, and only mxbM and mxbD mutants affected the final levels of PQQ significantly. PMID- 8002623 TI - [A case of peritoneal metastasis of breast cancer successfully treated by multidisciplinary therapy with hyperthermia therapy]. AB - A 53-year-old female with peritoneal metastasis of breast cancer was treated with hyperthermia with chemotherapy. One course consisted of THP 60 mg and FT 400 mg/iv (day 1), CPM 100 mg and MPA 800 mg/daily/po) with RF heating of hyperthermia monthly. After completion of 10 courses of this regimen, ascites completely disappeared and peritoneal metastases were not found observed in any peritoneal cavity with abdominal CT and ultrasound. Peritoneal metastasis of breast cancer was one of the worst reactions with any therapy. The patient has been living for about four years without any signs of recurrence, with the tumor markers within the normal range after surgery. Thermochemotherapy seems a very promising treatment modality for peritoneal metastasis of breast cancer. PMID- 8002625 TI - [Effect of 3-hydroxy-3-methylglutaryl coenzyme A(HMG-CoA) reductase inhibitor, pravastatin on liver metastasis of a pancreatic cancer cell line, SUIT-2 in nude mice]. PMID- 8002624 TI - [The two cases of examination of chemotherapy in advanced gallbladder carcinoma]. AB - Two cases of advanced carcinoma of gallbladder were treated by combination chemotherapy consisting of 5-FU, leucovorin and continuous administration of etoposide. One of the cases was a male 61 years old and another was a female 64 years old, both of whom were diagnosed as inoperable cases by imaging studies. When combination chemotherapy consisting of 5-FU (750mg/day or 1,000mg/day infusion) was given, leucovorin (30mg/day) and etoposide (25mg/day oral or 33mg/day continuous infusion), angiography or other imaging studies pointed out a reduction in their lesions of over 50%, and their QOL was markedly improved. PMID- 8002626 TI - [Effect of ME2303 in in vitro and liver metastatic model of nude mice on human pancreatic cancer cell line]. PMID- 8002627 TI - [Successful treatment of myelodysplastic syndrome with cytarabine ocfosfate]. PMID- 8002628 TI - [A novel antitumor agent, sobuzoxane (MST-16)]. AB - Sobuzoxane (MST-16) is an analogue of ICRF-159 which was once evaluated on the clinical efficacies in England. Zenyaku Pharm. Ind. in Japan synthesized many derivatives of bis (2,6-dioxopiperazine) and sobuzoxane was selected from the antitumor efficacies, the results of the toxicity tests and pharmacological profiles from these derivative. The compound was a new type topoisomerase II inhibitor, and G2M phase of the cell cycle was most sensitive. The clinical phase studies proved that sobuzoxane was quite effective for the treatment of malignant lymphoma (overall response rate in phase II study 29.7%) and adult T cell leukemia (response rate for acute type: 46.2%). The dose-limiting factor was leukopenia. PMID- 8002629 TI - [Interleukin-4 (IL-4)]. AB - Helper T cells can be divided into Th1 type cell which produces IL-2 and IFN gamma and Th2 type cell which produces IL-4, IL-5, and IL-6. In general, cytokine has a pleiotropic action. Furthermore cytokines have redundancy in their action. IL-4 is a major product of Th 2 type cell and is an essential cytokine for IgE production, which is also induced by recently found IL-13. Additionally IL-4 is a key factor for the development of Th2 cell, which produces cytokines responsible for inducing allergic reaction. In this paper, we described the gene regulation, molecular structure and biological action including the anti-tumor activity of IL 4. PMID- 8002630 TI - [Progress in heavy particle radiotherapy]. AB - In recent years, new types of ionizing radiations have been used as an attractive modality in cancer treatments. Low LET radiation such as protons and helium ions has the advantage of a high physical selectivity of irradiation. Clinical results have confirmed that they are of benefit in certain types of cancer. High LET particles such as fast neutrons, heavy ions (carbon, neon) and negative pions possess higher radiobiological effects (RBE). Moreover, the latter two particles have an advantage of improved dose distribution. The clinical indications for protons are those located in close vicinity to the critical normal organs, and those for fast neutrons are relatively superficial tumors. Further studies are needed to determine indications for pions. The available clinical experience in selected tumors with protons, pions and fast neutrons justifies the heavy-ion therapy programs. Successful results are anticipated from HIMAC (Heavy ion medical accelerator in Chiba) which is a dedicated facility for heavy-ion therapy. PMID- 8002631 TI - [Multidrug resistance (MDR)]. AB - Multiple drug resistance (MDR) is a major problem of current chemotherapy. Establishment of multiple drug resistant cell lines in culture and isolation of P glycoprotein-coding MDR genes have promoted understanding of the molecular mechanisms underlying drug resistance in tumors. Another gene, MRP, has been recently isolated from a multiple drug resistant cell line which did not express P-glycoprotein. Both genes have DNA sequence homology for each other and have been identified as members of ATP binding cassette (ABC) transporter superfamily. This review refers to recent progress in MDR and MRP study, and focuses on involvement of these two drug-resistance-related genes in acquiring drug resistance and their physiological functions. PMID- 8002632 TI - [Glutathione S transferases-pi]. AB - It has been known that many drug resistant factors including p-glycoprotein related to anticancer drug resistance. It is assumed that Glutathione s transferase (GST) is one of the resistant factors. In this present study, we examined the relationship between GST (especially GST-pi) and drug resistance, and also possibility of overcoming of drug resistance for GST-pi related drug resistance. We studied whether GST-pi directly related to anticancer drug resistance by transfection of GST-pi antisense cDNA into human colonic cancer cell line (M 7609). By transfection, cytosolic GST-pi concentrations decreased and sensitivity for adriamycin increased. It was confirmed that GST-pi directly related to some anticancer drug resistance including adriamycin. Moreover, we also have found that ketoprofen, which is an inhibitor of GST-pi activity, increased Adriamycin sensitivity. That is, partial overcoming of drug resistance was obtained. In future, it will be expected that GST-pi inhibitors etc are tried for overcoming of drug resistance. PMID- 8002634 TI - [MDR reversing drugs for clinical development]. AB - Since we discovered verapamil as an MDR-reversing agent in 1981, many MDR reversing compounds have been reported. This type of drug must be very effective but minimal side effects. We recently found that MS-209 and PSC-833 to be reversing agents that interact directly with P-glycoprotein and show good MDR reversing effect, both in vitro and in vivo. MS-209 and PSC-833 are thus interesting compounds for clinical use in future. PMID- 8002633 TI - [Recent progress in the study of the mechanism of resistance to DNA topoisomerase inhibitors]. AB - Altered DNA topoisomerase I and II have been shown in many cell lines resistant to topoisomerase inhibitors, showing that topoisomerases are main molecular targets of these inhibitors. In this paper, recent studies on the mechanism of resistance to DNA topoisomerase I and II inhibitors are reviewed. PMID- 8002635 TI - [Combined CDDP-THP-PEP chemotherapy (PTP therapy) for head and neck squamous cell carcinoma--a group study]. AB - A group study of chemotherapy for head and neck squamous cell carcinoma, using CDDP, THP and PEP, was carried out on 32 cases at the department of Otolaryngology, University of Tokyo, and 7 affiliated hospitals. The combined chemotherapy, which we call "PTP therapy", consisted of 30 mg/m2 of THP on day 1, 70 mg/m2 of CDDP on day 2, and 5 mg/body/day of PEP on 4 successive days. The overall response rate was 78.1% (CR: 15.6%; PR: 62.5%). No major side effect was observed in any case. PTP therapy is useful in neoadjuvant chemotherapy. PMID- 8002636 TI - [Experience with multidrug chemotherapy for patients with head and neck malignant tumors--comparison between CP therapy and PTP therapy]. AB - A combined chemotherapy regimen (CP chemotherapy) consisting of cisplatin (CDDP) and peplomycin (PEP) was employed to treat patients with head and neck malignant tumors. More recently, PTP chemotherapy added to CP chemotherapy with THP adriamycin (THP-ADM) was employed. We proceeded to investigate the efficacy of these two chemotherapeutic regimens. The subjects of this study included 22 patients in the CP chemotherapy group (18 males and four females). The PTP chemotherapeutic regimen was administered to 23 patients (18 males and five females). The results showed response rates of 54.5% for the CP chemotherapeutic regimen and 60.9% for the PTP chemotherapeutic regimen. In both treatment groups, the response rate decreased as the disease stage increased. As adverse reactions to the chemotherapeutic regimens, nausea and vomiting occurred in 63.6% of the CP group and 69.6% of the PTP group. Leukopenia was detected in 18.2% of the CP group and 69.6% of the PTP group, while alopecia was seen only in the PTP group, at an incidence of 39.1%. Cardiotoxicity was not detected in either group. PMID- 8002637 TI - [Tissue concentration of tegafur suppository in patients with head and neck cancer--concentration of 5-FU in cancer tissue]. AB - Fifty patients with head and neck cancer were treated with tegafur suppository for 7 days preoperatively. The tissues were obtained during surgical operation and the concentrations of 5-FU in cancer tissue, normal tissue and blood were measured. It was revealed that a high concentration of 5-FU was seen in cancer tissue and then metastatic lymph nodes. The 5-FU concentration in cancer tissue was parallel with T stage of the patients. Subsites which showed a high concentration of 5-FU were nasal-paranasal cavity, tongue and mesopharynx. The tegafur suppository was useful because of the high concentration in cancer tissue and metastatic lymph nodes without any obvious side effects in the head and neck region. PMID- 8002638 TI - [Multiple cooperative study of UFT-adjuvant chemotherapy for malignant tumor in the jaw and oral cavities. The Oral Surgery Malignant Tumor Research Association in Kanto Kohshinetsu District]. AB - We studied the usefulness and safety of long-term administration of uracil and tegafur (UFT) after primary therapy of the malignant tumor in jaw and oral cavity regions randomized controlled trial. 112 cases were totallized 6 institutes belonging to the Oral Surgery Malignant Tumor Research Association in Kanto Kohshinetsu District during 2 years and 10 months, beginning in September 1986. After completing the primary therapy, treatment was not performed in group A and 400 mg/day of UFT was orally administered in group B for 1 year. A variation was observed in the stages of background factors such as sex and age (more than 30 years old and less than 80 years old), while no such discrepancy was observed in other stages. No significant difference of 1-year-survival ratio and non recurrence ratio was noted in either group, while the non-recurrence ratio was more favorable in group B than group A, and the usefulness of UFT for adjuvant chemotherapy was suggested. The incidence of side effects in group B was 42.6%, and no serious side effect was observed. PMID- 8002639 TI - [Phase-I clinical study of KW-2307 combined with cisplatin in non-small cell lung cancer patients]. AB - A phase-I clinical study with coadministration of a new vinca alkaloid derivative KW-2307 with cisplatin (CDDP) at 80 mg/m2 to patients with non-small cell lung cancer was conducted by a collaborative study among 6 institutions. CDDP was given on day 1 and KW-2307 on days 1, 8 and 15, both intravenously. One 28-day course was specified to be repeated twice. The initial dose of KW-2307 was 15 mg/m2 and increased to 20 mg/m2 and then to 25 mg/m2. The numbers of enrolled subjects for each dose were 5, 8 and 12 cases, respectively, in the total 25 cases. This regimen as well as KW-2307 monotherapy induced leukocytopenia (neutropenia) as the main adverse reaction. The coadministration with CDDP tended to increase the occurrence of anorexia and nausea/vomiting. Tumor response was obtained in 5 among 24 evaluable cases (CR1, PR 4). The response rate in the cases untreated with KW-2307 and given at 20 mg/m2 or higher doses was 29.4% (5/17, 95% confidence interval of the response rate: 10.3 to 54.7%). Considering drug compliance, etc., the maximum tolerated dose in this regimen was supposed to be 25 mg/m2, and the recommended dose in phase-II study to be 20 mg/m2. PMID- 8002640 TI - Use of short-course class 1 topical glucocorticoid under occlusion for the rapid control of erythrodermic psoriasis. PMID- 8002641 TI - Dermatology in the Oregon plan with implications for health care plans in other states. AB - The Oregon Health Plan has been described and debated in several journals, but I would like to briefly outline dermatology's role in the plan and how dermatology patients will be affected. Lessons have been learned in Oregon that will be applicable to similar health plans in other states. PMID- 8002642 TI - Topical retinoic acid (tretinoin) for melasma in black patients. A vehicle controlled clinical trial. AB - BACKGROUND AND DESIGN: Melasma is an acquired, masklike, facial hyperpigmentation. The pathogenesis and treatment of melasma in black (African American) patients is poorly understood. We investigated the efficacy of topical 0.1% all-trans-retinoic acid (tretinoin) in the treatment of melasma in black patients. Twenty-eight of 30 black patients with melasma completed a 10-month, randomized, vehicle-controlled clinical trial in which they applied either 0.1% tretinoin or vehicle cream daily to the entire face. They were evaluated clinically (using our Melasma Area and Severity Index), colorimetrically, and histologically. RESULTS: After 40 weeks, there was a 32% improvement in the Melasma Area and Severity Index score in the tretinoin treatment group compared with a 10% improvement in the vehicle group. Colorimetric measurements showed lightening of melasma after 40 weeks of tretinoin treatment vs vehicle. Lightening of melasma, as determined clinically, correlated well with colorimetric measurements. Histologic examination of involved skin revealed a significant decrease in epidermal pigmentation in the tretinoin group compared with the vehicle group. Side effects were limited to a mild "retinoid dermatitis" occurring in 67% of tretinoin-treated patients. Among the patients in this study in comparison with comparably recruited white patients, melasma was reported to have begun at a later age and was more likely to be in a malar distribution. CONCLUSIONS: This controlled study demonstrates that topical 0.1% tretinoin lightens melasma in black patients, with only mild side effects. PMID- 8002643 TI - Specific pruritic diseases of pregnancy. A prospective study of 3192 pregnant women. AB - BACKGROUND AND DESIGN: For a period of 1 year, all pregnant women presenting with itching were investigated by clinical, histologic, immunopathologic, and laboratory studies. Fifty-one of 3192 pregnant women were studied. RESULTS: We identified (1) two typical cases of herpes gestationis, with an approximate incidence of one in 1700 pregnancies; (2) 22 cases of pruritus gravidarum, including five cases with a polymorphous skin eruption, with an incidence of one in 145 pregnancies; (3) 25 cases of polymorphic eruption of pregnancy, including diseases without maternal or fetal side effects and without criteria defining herpes gestationis or pruritus gravidarum, with an incidence of one in 130 pregnancies; and (4) two cases of intercurrent disease (one scabies and one exfoliative dermatitis). CONCLUSION: Our study is a prospective homogeneous account of pruritic dermatosis of pregnancy. Our results show that the incidence of herpes gestationis is higher than is usually reported in the literature and that pruritus gravidarum must be considered in the presence of itching occurring during pregnancy, with or without skin eruption. PMID- 8002644 TI - Topical 0.050% betamethasone dipropionate. Pharmacokinetic and pharmacodynamic dose-response studies in humans. AB - BACKGROUND AND DESIGN: Effective topical drug therapy requires drug delivery into the skin to produce the desired pharmacodynamic response. For topical corticosteroids, the visual skin-blanching assay has been used to rank the potency of the corticosteroids and their overall efficacy. While vehicles have been shown to influence the resulting blanching response, the dose of drug applied has not always produced proportional differences in the blanching assay. The mechanism of the nonproportional pharmacodynamic response to the corticosteroid dose is unclear. We describe four methods for assessing the dose response relationship of topical betamethasone dipropionate on the ventral forearm of six human subjects: duration, concentration, film thickness, and surface area. Drug uptake analysis in human stratum corneum and the resulting pharmacodynamic response, measured visually and with a chromameter, were performed with each method to quantify the dose-response relationship. RESULTS: Only the concentration and duration methods demonstrated an increase in mean drug uptake with increasing dose. The maximal mean pharmacodynamic response reflected the mean drug uptake with all four methods. Application conditions for maximal pharmacodynamic activity of topical betamethasone dipropionate in the skin include short duration of treatment (< or = 2 hours), a lower concentration than commercially marketed, and thin film thicknesses (1 to 5 microns). CONCLUSION: A dose response can be produced by increasing the drug concentration or the duration of application time. Achievement of steady-state betamethasone dipropionate uptake into the stratum corneum was not commensurate with the maximal pharmacodynamic response. Very small amounts of this potent corticosteroid within the skin appear to maximize the receptor response to drug. PMID- 8002645 TI - Inhibition of a model of in vitro granuloma formation by tetracyclines and ciprofloxacin. Involvement of protein kinase C. AB - BACKGROUND AND DESIGN: Granulomatous inflammation is a common component of many diseases. In this study the ability of commonly used antibiotics to inhibit an in vitro model of granuloma formation were studied. The effect of protein kinase C inhibition in this system was also investigated. RESULTS: Ampicillin, cephalothin, metronidazole, rifampin, isoniazide, erythromycin, and clindamycin were inactive in inhibiting granuloma formation. Tetracycline, doxycycline, minocycline, and ciprofloxacin produced dose-dependent inhibition of the granuloma model in concentrations between 10(-4) and 10(-6) mol/L. The approximate order of descending potency was doxycycline equals minocycline greater than tetracycline greater than ciprofloxacin. The same drugs were tested for the ability to inhibit protein kinase C. Drugs inactive in the granuloma model had no effect on protein kinase C activity. The tetracyclines and ciprofloxacin all caused a dose-dependent inhibition of protein kinase C activity in the same order of relative potency as was found for inhibition of granuloma formation. CONCLUSIONS: These data demonstrate a previously unappreciated activity of the tetracyclines and ciprofloxacin. Inhibition of granuloma formation helps to account for the activity of these drugs in the severest forms of inflammatory acne. PMID- 8002646 TI - Nicotinamide and tetracycline therapy of bullous pemphigoid. AB - BACKGROUND AND DESIGN: The combination of nicotinamide and tetracycline has been anecdotally reported to be effective in the treatment of bullous pemphigoid. We conducted a randomized, open-labeled trial comparing the combination of 500 mg of nicotinamide, three times daily, and 500 mg of tetracycline four times daily, with prednisone therapy in 20 patients with bullous pemphigoid. The study was divided between an 8-week acute phase with fixed drug dosages and a 10-month follow-up phase in which study medications were tapered based on patient response. RESULTS: Eighteen of 20 patients enrolled in the study were treated, two patients were unavailable for follow-up. Twelve patients were treated with the combination of nicotinamide and tetracycline and six patients were treated with prednisone. There were five complete responses, five partial responses, one nonresponder, and one patient with disease progression in the nicotinamide and tetracycline group compared with one complete response and five partial responses in the prednisone group. There were no statistically significant differences in response parameters between the two groups. All five patients in the nicotinamide and tetracycline group receiving long-term follow-up remained disease free during medication tapering, while three patients in the prednisone group had repeated disease flare-ups with steroid tapering. Adverse effects in the nicotinamide and tetracycline group included gastrointestinal upset (two patients) and transient renal failure (one patient). In the prednisone group, there was one occurrence each of hypertension, erosive gastritis, multiple decubitus ulcers, osteomyelitis, deep venous thrombosis, and death related to sepsis. Two patients required insulin therapy for hyperglycemia. CONCLUSIONS: The combination of nicotinamide and tetracycline appears to be a useful alternative to systemic steroids in the treatment of bullous pemphigoid. PMID- 8002647 TI - Idiopathic phalangeal osteolysis. AB - BACKGROUND: The acro-osteolytic diseases are a heterogeneous group of bone disorders characterized by bone resorption. Acquired and genetic forms have been well described. As hand abnormalities are frequently encountered in dermatologic practice, bone resorptive states, with particular reference to the idiopathic osteolytic disorders, are discussed. OBSERVATIONS: Asymptomatic terminal phalangeal osteolysis has been investigated in two unrelated young adults with no other bony or systemic abnormalities. The nails of the attenuated bulbous fingers were dystrophic, and pigmentary changes were present in the affected areas. The skin was otherwise normal, and there was minimal soft-tissue loss. Roentgenograms of the hands and feet showed varying stages of phalangeal osteolysis. CONCLUSIONS: Both cases represent primary idiopathic acro-osteolysis, as the bony changes are limited to the distal phalanges of the hands and feet. There were no features in the history or clinical evaluation to support a diagnosis of secondary acro-osteolysis. PMID- 8002648 TI - Follicular degeneration syndrome in men. AB - BACKGROUND AND DESIGN: Follicular degeneration syndrome (FDS, formerly called hot comb alopecia) has only been described in black women. The clinical and histologic features of eight black men with a scarring alopecia resembling FDS were studied. OBSERVATIONS: All eight men had evidence of scarring alopecia, which was most prominent on the crown of the scalp. None of the men were using chemical or physical modalities to straighten or style the hair. Overall, this group of men had more evidence of active inflammation than did the previously described women with FDS. The histologic features in the men were identical to those found in women with FDS. The presence of premature desquamation of the inner root sheath and migration of the hair shaft through the outer root sheath serve as histologic markers of FDS and separate it histologically from other forms of scarring alopecia. CONCLUSIONS: Follicular degeneration syndrome is a common form of scarring alopecia in black men, just as it is in black women. In men, there is no association between chemical or mechanical hair styling techniques (eg, the "hot comb") and onset, progression, or severity of disease. The histologic features of FDS in men are identical to those in women. PMID- 8002649 TI - Postmenopausal frontal fibrosing alopecia. Scarring alopecia in a pattern distribution. AB - BACKGROUND: Recession of the frontal hairline is a common event in postmenopausal women. This has been shown not to be a marker of gross androgenization, and is usually a progressive nonscarring alopecia. Six postmenopausal women, who developed a progressive frontal scarring alopecia, were studied and their clinical and laboratory data, as well as the results of scalp biopsy specimens in all six patients, were analyzed and compared with recognized forms of scarring alopecia and recently described findings in androgenetic alopecia. OBSERVATIONS: The six postmenopausal women developed a progressive frontal hairline recession that was associated with perifollicular erythema within the marginal hairline, producing a frontal fibrosing alopecia extending to the temporal and parietal hair margins. Scalp biopsy specimens from the frontal hair margin showed perifollicular fibrosis and lymphocytic inflammation concentrated around the isthmus and infundibular areas of the follicles. Immunophenotyping of the lymphocytes showed a dominance of activated T-helper cells. Clinical review of all six cases showed a progressive marginal alopecia without the typical multifocal areas of involvement seen in lichen planopilaris or pseudopelade. None of the patients had mucous membrane or skin lesions typical of lichen planus. Hormonal studies, in five patients, showed no elevated androgen abnormalities. CONCLUSIONS: Progressive frontal recession in postmenopausal women may show clinical features of a fibrosing alopecia. The histologic findings are indistinguishable from those seen in lichen planopilaris. However, the absence of associated lesions of lichen planus in all six women raises the possibility that this mode of follicular destruction represents a reaction pattern triggered by the events underlying postmenopausal frontal hairline recession. PMID- 8002650 TI - Rudimentary meningocele presenting with a scalp hair tuft. Report of two cases. AB - BACKGROUND: Rudimentary meningoceles represent a developmental anomaly in which meningothelial elements are found in the skin. The majority of rudimentary meningoceles occur on the scalp over the occiput or along cranial suture lines. They are usually recognized at birth and present as a pink papule or nodule or an area of alopecia. OBSERVATIONS: We present two patients who presented with a scalp hair tuft at birth over a rudimentary meningocele. This finding has not been previously reported. CONCLUSIONS: Rudimentary meningoceles are uncommon developmental anomalies that are of clinical importance due to the occasional presence of connection to the central nervous system. Due to this potential for central nervous system connection, any midline lesion in an infant, including midline hair tufts, deserves careful preoperative evaluation including imaging studies. PMID- 8002652 TI - Dermatology and the evolution of therapies to control inflammatory tissue injury. PMID- 8002651 TI - Specific dermatoses of pregnancy. Toward a comprehensive view? PMID- 8002653 TI - Indurated plaques and persistent ulcers in an HIV-1 seropositive man. Silicone granulomas (reaction to silicone injection). PMID- 8002654 TI - Generalized pruritus with flexural micropapules in a 16-month-old girl. Fiberglass dermatitis. PMID- 8002655 TI - Fungating pustular plaques in a patient with Graves' disease. Iododerma. PMID- 8002656 TI - Localized pustular skin eruption. Localized pustular drug eruption secondary to ampicillin. PMID- 8002658 TI - Lipedematous scalp. PMID- 8002657 TI - Pruritic urticarial papules and plaques of pregnancy: relationship to maternal weight gain and twin or triplet pregnancies. PMID- 8002659 TI - Fluoxetine-induced hypersensitivity. PMID- 8002660 TI - Inadvertent phototoxicity from home tanning equipment. PMID- 8002661 TI - Sunlight avoidance and cancer prevention in xeroderma pigmentosum. PMID- 8002662 TI - Bullous photodermatosis after lomefloxacin. PMID- 8002663 TI - Enhancement of PUVA phototoxic effects following celery ingestion: cool broth also can burn. PMID- 8002664 TI - Decreased bradykinin binding sites in fibroblasts from progressive systemic scleroderma. AB - The numbers of bradykinin receptors (BK-R) in cultured dermal fibroblasts from patients with progressive systemic sclerosis (PSS) and from healthy controls were measured using a receptor binding assay. The numbers of BK-R were significantly fewer in PSS fibroblasts than in control fibroblasts (P < 0.02). However, no differences in affinity were observed in BK-R between PSS and control fibroblasts. The BK-R mRNA levels were determined in PSS and control fibroblasts by Northern blot hybridization using BK-R cDNA, but no significant differences were found. These findings suggest that the decrease in BK-R in PSS fibroblasts might occur during a posttranslational step. PMID- 8002665 TI - UVB irradiation reduces the expression of pemphigoid antigens in organ-cultured normal human skin. PMID- 8002666 TI - [Bone lithiasis: experimental and clinical histopathology]. AB - There is scant literature on bone lithiasis, a disease entity whose diagnosis depends fundamentally upon the anatomopathological findings. The data gleaned from animal experiments have been shown to overlap with those observed in the clinical setting. Conservative treatment should include resection of the urothelial bony metaplasia to avoid recurrence. The importance of making a correct diagnosis cannot be overemphasized since this condition may be associated with a tumoral lesion and a close follow-up is therefore warranted. PMID- 8002667 TI - [Ureteral reimplantation with single point on tubularized ileal chimney in Studer's substitution enterocystoplasty. Preliminary results in 12 cases]. AB - Herein we describe our preliminary experience in ureteral reimplantation by fixation of the ureter with a single suture directly onto a detubularized ileal chimney in 12 cases with infiltrating bladder carcinoma who underwent a Studer enterocystoplasty procedure. Follow up ranged from 3 to 24 months. Patient control evaluation included urography and CUMS 3 months postoperatively and ultrasonography every 6 months. The following complications were observed: ureteral fistula above the site of anastomosis (1 case, 4.16%), ureteroenteric stricture (1 case, 4.16%) and grade 2 reflux (2 cases, 9.08%) with no effects on renal morphology or function. The foregoing results show the usefulness of this simple procedure which prevents reflux and carries a low complication rate. PMID- 8002668 TI - [Spontaneous retroperitoneal hemorrhage]. AB - We report three cases of spontaneous retroperitoneal hemorrhage; two patients had a ruptured angiomyolipoma and one had a Wunderlich's syndrome. They had presented with the so called Lenk's triad. The definitive diagnosis was made on the CT findings and treatment was by nephrectomy (cases 1 and 2) and simple evacuation of the hematoma (case 3). The clinical, diagnostic and therapeutic aspects are briefly discussed. PMID- 8002669 TI - [Renal carcinoma with tumor embolism of the supradiaphragmatic inferior vena cava: therapeutic alternatives and review of the literature]. AB - We report a case of a man with a left renal cancer and vena caval thrombus extending to the right atrium, that was not possible to remove because infiltration of the posterior plane was detected intraoperatively. The patient was rehospitalized for intractable haematuria. He underwent selective embolization of the left renal artery with ethanol and coil. There were no complications and the patient is well seven months after the procedure. We review the literature on the diagnostic and therapeutic options in such cases. We can conclude that it is necessary to know the exact stage of the primary cancer in order to choose the best treatment. MRI or dynamic CT should be utilized to determine the presence of infiltration of adjacent structures or distant metastasis. Radical nephrectomy and the removal of the caval thrombus afford the only possibility of survival in these patients. PMID- 8002670 TI - [Biochemical effects of potassium citrate in the treatment of calcium oxalate lithiasis]. AB - The serum and urinary biochemical changes observed one month and six months after oral potassium citrate therapy (600 mEq/day) in 119 patients with calcium oxalate calculi were compared with those of 16 untreated cases with lithiasis. The patients that received treatment were previously divided into two groups: group A comprised 61 hypocitraturic patients and group B comprised 58 patients with other urinary disorders who were normo or hypocitraturic. The urinary pH increased by approximately half a point in both treated groups. In group A calciuria increased slightly from 180 +/- 8 to 216 +/- 10 mg/24 h but remained within the normal ranges. Creatinuria, oxaluria, uricosuria and diuresis showed no changes. Citraturia increased very significantly in both groups and more markedly in the hypocitraturic group of patients (from 198 +/- 13 to 476 +/- 35 mg/24 h). The LRC (lithogenic risk coefficient = Ca/Cit x Diu) dropped by 50%. The patients tolerated the treatment regimen well; of the 119 treated patients, only 11 abandoned treatment due to GI intolerance. PMID- 8002671 TI - [Ambulatory treatment of urinary lithiasis with extracorporeal lithotripsy (Dornier MFL-5000): comparative study of its use with low and high kilovoltages]. AB - The present study compared the results achieved with ESWL using the Dornier MFL 5000 lithotriptor in 133 patients who received analgesics alone during treatment versus 141 patients who received analgesics plus sedation with midazolam. Both patient groups received the maximum tolerated energy and shock waves necessary to fragment the calculi. The patients who received analgesics plus midazolam tolerated the maximum energy of the lithotriptor (30 Kv), which permitted reducing the total number of shock waves required for fragmentation by 49%. Furthermore, the number of retreatments dropped by 38% (1.15 versus 1.53 sessions per renal unit) and the time required for treatment was reduced by 40% (p < 0.01). PMID- 8002672 TI - [Perirenal hematoma after ESWL in a patient with stage T1 renal tumor]. AB - We report a case of perirenal hematoma post ESWL in a patient with controlled hypertension and a previously undiagnosed stage T1 kidney neoplasm. The foregoing complication can be partly ascribed to the renal tumor. It must therefore be taken into account that a small kidney mass may be overlooked during urography and consequently an ultrasound study of the kidney should be done before the patient is submitted to X-ray-guided lithotripsy. PMID- 8002673 TI - [Extracorporeal shockwave lithotripsy on a clam shell fragment lodged in the ileocecal valve]. AB - Herein we describe what may be the first case of ESWL used in the treatment of mechanical ileus caused by a fragment of clam shell lodged in the terminal ileum. The 66-year-old patient was referred by the emergency department with symptoms and signs of upper GI tract obstruction. ESWL with the modified Dornier HM3 was performed under neuroleptoanalgesia with the patient in the prone decubitus position. 1700 shock waves at 20 Kv were used to achieve fragmentation and restore intestinal transit, thus avoiding surgery. PMID- 8002674 TI - [Idiopathic scrotal gangrene. Report of 2 cases]. AB - The literature on the etiology, clinical features and treatment of idiopathic gangrene of scrotum or Fournier's gangrene is briefly reviewed. Two cases that had been treated at the urological services of the 10 de Octubre teaching hospital in Havana (Cuba) are described, with special reference to treatment of this uncommon disease entity by drainage and surgical debridement of the compromised area and antibiotic therapy. PMID- 8002675 TI - [Pure prostatic leiomyoma]. AB - We report a case of pure leiomyoma of the prostate, an uncommon benign tumor with a leiomyomatous component distinct from benign prostatic hyperplasia. The literature is reviewed and several considerations are put forward relative to the etiopathogenesis, clinical and anatomopathological features, differential diagnosis and prognosis of this tumor. PMID- 8002677 TI - [Partial nephrectomy for pyelo-renal duplication with pseudocoraliform lithiasis in non-functioning upper pyelon]. AB - We performed a right heminephrectomy in a patient with pyelorenal duplicity, pseudostaghorn stone in nonfunctioning superior pyelon and a history of right perirenal abscess. The history, indications, variations and complications of this surgical procedure are briefly described. The importance of performing a complete evaluation prior to surgery is emphasized. PMID- 8002676 TI - [Leiomyoma of the epididymis. Report of a case and review of the literature]. AB - Leiomyoma of the epididymis is a benign tumor that is rarely diagnosed and is second only to epididymal adenomatoid lesions in frequency. A case of leiomyoma of the epididymis in a 62-year-old patient is described. The patient presented with a tumor in the tail of the left epididymis which was definitively diagnosed following surgical resection and subsequent anatomopathological analysis. The classification, clinical features, diagnosis and treatment of this tumor type are briefly discussed. PMID- 8002678 TI - [Pseudo-tuberculous pyelonephritis]. AB - We report on a 67-year-old woman with caseating granulomatous pyelonephritis associated with nephrolithiasis. Caseating granulomas resembling renal tuberculosis were observed in the renal parenchyma, but no TB or other microorganisms were detected in the renal tissue or urine cultures. To our knowledge, this is the second case reported in the literature. PMID- 8002679 TI - [Unilateral ureteral hernia. Report of a case]. AB - Hernia of the ureter is an uncommon condition and may classified into two types in relation to the peritoneum: extraperitoneal (without hernial sac) and paraperitoneal (with permeable peritoneum and redundant sac). This condition is generally asymptomatic and may be detected incidentally during urography or herniorrhaphy. We report on a case that had been detected during radiologic control evaluation of a left percutaneous nephrostomy prior to treatment with ESWL of a calculus in the ipsilateral lumbar ureter. PMID- 8002680 TI - [Bladder amyloidosis in a female patient with suspected bladder carcinoma]. AB - We report on a patient with a long history of rheumatoid arthritis who consulted for intense hematuria that was initially ascribed to carcinoma of the bladder. Subsequent patient evaluation, however, disclosed amyloidosis of the urinary bladder. The literature on amyloidosis of the urinary tract is reviewed. A detailed analysis of the biopsy specimens taken from a lesion that looks like a bladder carcinoma may disclose other pathologies such as amyloidosis of the urinary bladder. PMID- 8002681 TI - Steroid receptors in prostate cancer tissues and cells: pathophysiology, problems in methodology, clinical value and controversial questions. AB - This paper reviews basic and clinical aspects of human prostate cancer, with special regard to steroid hormones and growth factors, their receptors and the use of these tools in clinical practice. Unlike other endocrine-related tumours, such as breast and endometrial cancer, human prostatic carcinoma has distinctive features that crucially hinder its definition in terms of both biological potential and clinical course. Failure of androgen receptors to represent helpful discriminants for both prognosis and treatment of prostate cancer patients may depend upon methodological pitfalls and/or the heterogeneous composition of most tumour tissues. The former involve either technical problems (tissue sampling and storage, assay procedures) or biochemical and biological points (heterogeneity and functional integrity of steroid binding sites, subcellular and tissue distribution of steroid receptors). The latter mostly concern the unique feature of both normal and diseased prostate gland to present regional diversities in hormone sensitivity and steroid receptor content. Another important area of interest resides in the potential role played by stromal-epithelial interaction in the regulation of growth and function of prostate epithelial cells. In this respect, continued growth of androgen-dependent prostate cancer cells is achieved through intricate pathways where mesenchymal steroid-induced polypeptide growth factors may act in a paracrine/autocrine fashion to mediate androgen action on tumor epithelial cells. In particular, epidermal growth factor (EGF) and transforming growth factor-a (TGFa) may serve as androgen intermediaries in the proliferative control of prostate epithelial cells, but may also be involved in androgen-independent autocrine epithelial cell growth. Clinical correlations of androgen receptors in human prostatic carcinoma have been insofal disappointing. Biochemical or histochemical assays have failed to satisfactorily predict prognosis and response to endocrine therapies of patients. This recalls problems in both methodologies and tissue suitability and points to the need of prolonged follow-up studies wherein special care is placed in sampling conditions, identification of high-affinity sites of steroid binding and selection of threshold values for receptor concentrations. Assay of the EGF receptors might provide additional contribution for a deeper inspection of the biological nature of prostate tumour tissues and help in selecting more appropriate individual based therapeutic strategies. PMID- 8002682 TI - Idiopathic deep venous thrombosis. Is a search for malignant disease justified? PMID- 8002683 TI - Cholesterol and violent behavior. AB - Despite significant decreases [corrected] in the incidence of myocardial infarction, reduction of total mortality as a result of cholesterol-lowering programs has not been demonstrated. This puzzling outcome has led to several hypotheses linking cholesterol levels and mortality due to accidents, suicide, and homicide. We review the proposed explanations for increased mortality due to violent deaths. We discuss the available evidence and conclude that while there are some intriguing findings based on the well-established relationship between violent behavior and serotonin activity, the necessary link between cholesterol, serotonin, and violence has not been demonstrated. The complexity of the observed violent behaviors and their multiple determinants defies a simple explanation at the present time. PMID- 8002684 TI - Medical, metabolic, and psychological effects of weight cycling. AB - This article reviews studies on the effects of weight cycling and weight variability on metabolism, psychological status, morbidity, and mortality. Repeated bouts of weight loss and regain, known as weight cycling or yo-yo dieting, are highly prevalent, occur in males and females, and are common in both overweight and nonoverweight individuals. While there has been no consistent demonstration that, as was first thought, weight cycling makes subsequent weight loss more difficult or regain more rapid, it is possible that this does occur under some conditions or in particular individuals. There are stronger and more consistent links between body weight variability and negative health outcomes, particularly all-cause mortality and mortality from coronary heart disease. Weight cycling may also have negative psychological and behavioral consequences; studies have reported increased risk for psychopathology, life dissatisfaction, and binge eating. The bulk of epidemiologic research shows an association of weight variability with morbidity and mortality, although the mechanisms are not clear at present. There is a clear need for further research on the effects of weight cycling on behavior, metabolism, and health. Understanding and promoting weight maintenance is an important priority. PMID- 8002686 TI - Comparison of patients' compliance with prescribed oral and inhaled asthma medications. AB - BACKGROUND: Noncompliance with medications is one of the most serious problems facing health care today. However, methods to measure compliance have many limitations. METHODS: To measure specific drug compliance and dosing frequency of two asthma medications, we used medical records data and pharmacy claims data from 276 patients who had concurrent prescriptions for inhaled anti-inflammatory agents and oral theophylline. Patients were randomly selected from the pharmacy claims data files of a health maintenance organization. The patients' medical records were reviewed, and records that did not contain clear documentation of the medication, dose, and dosing frequency were excluded. Data from the remaining 119 medical records were compared with data from pharmacy claims to calculate compliance rates for each medication. RESULTS: Our calculations showed that patients were significantly more compliant with prescribed theophylline medication than with two inhaled anti-inflammatory medications (P = .0001). No significant differences in compliance were found relative to prescribed dosing frequency (twice daily or less compared with three times daily or more) for either medication (P = .6517). CONCLUSIONS: Comparison of medical record data with pharmacy claims data is an effective indirect measure of patients' compliance with prescribed oral theophylline and inhaled anti-inflammatory agents. Additional interventions must be pursued for patients with asthma regarding adherence to regimens for their prescribed inhaled anti-inflammatory agents. PMID- 8002685 TI - The risk of myocardial infarction associated with the combined use of estrogens and progestins in postmenopausal women. AB - BACKGROUND: While observational studies have suggested that unopposed estrogens reduce the incidence of coronary disease in postmenopausal women, there are few data on the effect of combined therapy with estrogens and progestins--a regimen adopted in recent years to minimize the risk of endometrial hyperplasia and cancer. In clinical trials, the addition of progestins has an adverse effect on serum lipid levels, and these lipid effects have raised the question of whether combined estrogen-progestin therapy increases the risk of coronary disease compared with the use of estrogen alone. METHODS: We conducted a population based, case-control study among enrollees of Group Health Cooperative of Puget Sound. Cases were postmenopausal women who sustained an incident fatal or nonfatal myocardial infarction in 1986 through 1990. Controls were a stratified random sample of female Group Health Cooperative enrollees frequency matched to the cases by age and calendar year. We reviewed the medical records of the 502 cases and 1193 controls and conducted brief telephone interviews with consenting survivors. The health maintenance organization's computerized pharmacy database was used to ascertain the use of postmenopausal hormones. For the primary analysis of current use, we classified women into one of three groups: (1) nonusers of hormones; (2) users of estrogens alone; or (3) users of combined therapy including both estrogens and progestins. Each group of hormone users was compared with nonusers. RESULTS: After adjustment for potential confounding factors, the risk ratio of myocardial infarction associated with current use of estrogens alone was 0.69 (95% confidence interval, 0.47 to 1.02); and the risk ratio of myocardial infarction associated with current use of combined therapy was 0.68 (95% confidence interval, 0.38 to 1.22). Duration of combined-therapy use was relatively short, averaging less than 2 years in cases and controls. CONCLUSIONS: In this case-control study, the reduced risk of myocardial infarction associated with the use of estrogens alone was consistent with previous observational studies. Although the 95% confidence interval only excluded a risk above 1.22, the current use of combined therapy was not associated with an adverse effect on the incidence of myocardial infarction in postmenopausal women. PMID- 8002687 TI - Mycobacterium marinum skin infections. Report of 31 cases and review of the literature. AB - BACKGROUND: Mycobacterium marinum is a rare cause of skin infections, and its treatment has been based primarily on the personal experience and preferences of individual investigators without the benefit of large studies. METHODS: Thirty one patients with confirmed M marinum infection were identified at 33 Kaiser Permanente Northern California Region medical centers by microbiologic records, and their charts were reviewed. RESULTS: The upper extremity was affected in 90% of cases, and lymphatic or local spread was seen during the initial examination or during observation in 25 patients (81%). Granuloma was present in 22 (63%) of 35 biopsy specimens, and staining for acid-fast bacteria yielded positive results in two of 22 specimens. Cure or improvement occurred in 22 (81%) of 27 patients in whom outcome could be evaluated. Treatment with ethambutol plus rifampin appeared more successful (effective in five [100%] of five cases) than minocycline treatment (effective in 10 [71%] of 14 cases), although not significantly so (P = .28). Adverse reactions, most of which were gastrointestinal, occurred in five patients (18%). CONCLUSION: Ethambutol plus rifampin appears more useful than minocycline in treating cutaneous M marinum infection. This result remains to be confirmed by larger clinical studies, which may be difficult because this infection is relatively rare. PMID- 8002688 TI - The doctor-patient relationship and malpractice. Lessons from plaintiff depositions. AB - BACKGROUND: The current literature does not provide an answer to the question, "What prompts patients to sue doctors or hospitals?" Not all adverse outcomes result in suits, and threatened suits do not always involve adverse outcomes. The exploration of other factors has been hampered by the lack of a methodology to contact plaintiffs and elicit their views about their experience in delivered health care. This study employed the transcripts of discovery depositions of plaintiffs as a source of insight into the issues that prompted individuals to file a malpractice claim. METHODS: This study is a descriptive series review of a convenience sample of 45 plaintiffs' depositions selected randomly from 67 depositions made available from settled malpractice suits filed between 1985 and 1987 against a large metropolitan medical center. Information extracted from each deposition included the alleged injury; the presence of the question, "Why are you suing?" and, if present, the answer; the presence of problematic relationship issues between providers and patients and/or families and, if present, the discourse supporting it; the presence of the question, "Did a health professional suggest maloccurrence?" and, if yes, who. Using a process of consensual validation, relationship issues were organized into groups of more generalized categories suggested by the data. Answers to the questions, "Why are you suing?" and "Who suggested maloccurrence?" are described. RESULTS: Problematic relationship issues were identified in 71% of the depositions with an interrater reliability of 93.3%. Four themes emerged from the descriptive review of the 3787 pages of transcript: deserting the patient (32%), devaluing patient and/or family views (29%), delivering information poorly (26%), and failing to understand the patient and/or family perspective (13%). Thirty-one plaintiffs were asked if health professionals suggested maloccurrence. Fifty-four percent (n = 17) responded affirmatively. The postoutcome-consulting specialist was named in 71% (n = 12) of the depositions in which maloccurrence was allegedly suggested. CONCLUSIONS: In our sample, the decision to litigate was often associated with a perceived lack of caring and/or collaboration in the delivery of health care. The issues identified included perceived unavailability, discounting patient and/or family concerns, poor delivery of information, and lack of understanding the patient and/or family perspective. Particular attention should be paid to the postadverse-event consultant-patient interaction. PMID- 8002689 TI - Carotid stenosis in patients with atrial fibrillation. Prevalence, risk factors, and relationship to stroke in the Stroke Prevention in Atrial Fibrillation Study. AB - BACKGROUND: Several mechanisms contribute to the increased stroke rate of patients with atrial fibrillation (AF). We assessed the frequency of carotid artery stenosis in patients with AF and its relationship to stroke during aspirin or warfarin therapy. METHODS: Carotid ultrasonography was done in 676 patients with AF enrolled in the Stroke Prevention in Atrial Fibrillation Study to detect cervical carotid stenosis of 50% or more of the luminal diameter. The presence of carotid stenosis was correlated with patient features and subsequent stroke during a mean of 2.6 years of follow-up. RESULTS: In patients with AF who were older than 70 years, the frequency of carotid stenosis was 12% in men and 11% in women. Carotid stenosis was independently associated with systolic hypertension (relative risk, 2.4; P = .002), diabetes (relative risk, 1.8; P = .04), and tobacco use (relative risk, 1.8; P = .02). Carotid stenosis did not add significantly to prediction of stroke when analyzed with other clinical risk factors for stroke in patients with AF (relative risk, 1.3; 95% confidence interval, 0.5 to 3.6; P = .55). CONCLUSIONS: Carotid artery stenosis of 50% or more occurs in about 12% of elderly patients with AF, reflecting the substantial prevalence of hypertension and diabetes in these patients. Carotid stenosis was not usefully predictive of stroke in patients with AF who were given aspirin or warfarin. Routine ultrasonography to detect carotid stenosis does not appear warranted in patients with AF without previous symptoms of brain ischemia. PMID- 8002690 TI - Efficacy of nonsteroidal anti-inflammatory drugs in the treatment of acute renal colic. A meta-analysis. AB - OBJECTIVE: To evaluate the efficacy of nonsteroidal anti-inflammatory drugs (NSAIDs) compared with placebo or analgesic agents in the treatment of acute renal colic. DATA SOURCES: The MEDLINE and EMBASE databases were searched using the following terms: anti-inflammatory agent, colic, kidney diseases, and ureteral diseases. The Family Medicine Library Index, references of retrieved articles, and documentation centers of pharmaceutical companies were also consulted. STUDY SELECTION: Among 60 retrieved articles, 19 were selected by consensus of a group of four physicians, based on the following criteria: randomized controlled trials, NSAID compared with placebo or analgesic agent in the treatment of acute renal colic, and articles written in either French or English. DATA EXTRACTION: Independent data extraction by four evaluators using a 20-item checklist. Final assessment was by group consensus. DATA SYNTHESIS: The 19 articles presented 20 studies, most comparing parenteral diclofenac or indomethacin (18 of 20) with placebo (n = 4) or analgesic agents (n = 16), most of which were narcotic agents. The results of pain relief 20 to 30 minutes after drug administration were pooled using the Mantel-Haenszel method for three distinct groups of studies: (1) NSAIDs vs placebo (n = 4): relative risk (RR), 2.34 (95% confidence interval [CI], 1.79 to 3.07); (2) NSAIDs vs analgesic agents, partial pain relief (n = 9): RR, 1.07 (95% CI, 1.02 to 1.12); and (3) NSAIDs vs analgesic agents, complete pain relief (n = 9): RR, 1.19 (95% CI, 1.03 to 1.37). CONCLUSIONS: Parenteral NSAIDs are more effective than placebo and as effective as analgesic agents in the treatment of acute renal colic. PMID- 8002691 TI - Human immunodeficiency virus infection in long-distance truck drivers in east Africa. AB - BACKGROUND: A cross-sectional survey was performed to determine the seroprevalence and correlates of human immunodeficiency virus (HIV) infection among long-distance truck drivers in Kenya. METHODS: Truck drivers along the Mombasa-Nairobi highway were enrolled at a roadside research clinic. A standardized interview and serologic evaluation for HIV and syphilis were conducted. RESULTS: We enrolled 970 truck drivers and their assistants of whom 257 (27%) had HIV antibodies. In univariate analysis, HIV infection was correlated with older age, non-Kenyan nationality, Christian religion, longer duration of truck driving, travel outside of Kenya, less frequent visits to wives, and more frequent visits to prostitutes. Uncircumcised status, history of genital ulcer disease or urethritis during the previous 5 years, and a positive Treponema pallidum hemagglutination assay for syphilis were each associated with positive HIV serostatus. Univariate correlates of uncircumcised status included younger age, non-Kenyan nationality, Christian religion, travel outside of Kenya, and less frequent visits to prostitutes. There was a significant association between uncircumcised status and 5-year history of genital ulcer disease or serologic evidence of syphilis, but not with 5-year history of urethritis. In multivariate analysis, HIV infection was independently associated with uncircumcised status (adjusted odds ratio [OR], 4.9; 95% confidence interval [CI], 2.8 to 8.4), history of genital ulcer disease (adjusted OR, 2.4; 95% CI, 1.5 to 4.1), history of urethritis (adjusted OR, 1.8; 95% CI, 1.1 to 2.9), more frequent sex with prostitutes (more than once per month; adjusted OR, 1.7; 95% CI, 1.1 to 2.8), and positive T pallidum hemagglutination assay (adjusted OR, 1.2; 95% CI, 1.0 to 1.4). The attributable risk percentage for the association between HIV and uncircumcised status was 70%, and the population attributable risk was 25%. CONCLUSIONS: Truck drivers in east Africa are at high risk of HIV infection. The strongest correlates of HIV seropositivity were uncircumcised status and history of both ulcerative and nonulcerative sexually transmitted diseases. PMID- 8002692 TI - Adult Kawasaki disease. Report of two cases treated with intravenous gamma globulin. AB - There are 36 reports in the English-language literature of Kawasaki disease in adults. We present two additional cases, in one of which retinal vasculitis developed, a previously unreported complication antemortem. We report the first use of intravenous gamma globulin in the United States for treatment of adult onset Kawasaki disease and review the pertinent literature. PMID- 8002694 TI - Antidepressants and tinnitus. PMID- 8002695 TI - Familial Mediterranean fever in Mexico City: 10-year follow-up. PMID- 8002693 TI - Epidural abscess due to acute Brucella melitensis infection. PMID- 8002696 TI - [Food consumption of school children regarding their social condition. Cordoba, Republic of Argentina]. AB - This report reveals the daily consumption of nourishing food in primary school children coming from the north of Cordoba, Argentina, in relationship with their socio economic status, SES. Four categories were determined according to the place the chief support of the family occupies in the productive system. A 24 hours recall test was applied to obtain nutritional data as well as the weight and method of measure. Differences among the established categories were pointed out by socioeconomic indicators (P < 0.001). Powder and liquid milk ingesta showed statistic differences (P < 0.005), at the same time, the consumption of this food was poor, and it was not being incorporated into the scholarship's diet. The per-capita proportion of meat ingesta was over 100 g, in the whole group. Difference (P < 0.005) were noticed among the SES when the consumption was over 200 g. The consumption of fruits and vegetables is low. On the contrary, it was shown an increase in cereals and legumes ingesta as the SES decreased (P < 0.005). Analyzing the fitness of the diet it was found that the 53% of SES IV children showed calorie shortage whereas the proteins evaluation revealed excess consumption in the 88% of the studied scholarships. Other deficiencies were also found, such as calcium, riboflavin, thiamine, niacin in the whole group. This study also showed statistic differences with respect to the consumption of energy, calcium and ascorbic acid (P < 0.05). PMID- 8002697 TI - Vitamin C load test in elderly subjects. AB - Ascorbic acid fasting serum levels and levels after a test dose were carried out in a group of elderly subjects: nine men with 70 +/- 6 years and six women 74 +/- 7 years old. They live in the same old folks home and ate similar food. Their ascorbic acid intake was found to be around 20 mg/day. Fasting serum levels found lower values in the women. A load test showed a small increase in the hourly samples, supporting low tissue reserves of the vitamin. Factors such as low intake, absorption, metabolism, body mass and/or excretion of the vitamin in elderly population could explain these results. A marginal vitamin C deficiency is believed to be present in the group and extra ascorbic acid food supply seems to be recommended for these subjects. PMID- 8002698 TI - Comparative effects of rose hip and corn oils on biliary and plasma lipids in rats. AB - The comparative effects of dietary level and time of feeding corn (CO) and rose hip (RHO) oils on bile and plasma lipid composition were studied. 48 males Sprague Dawley rats were divided in two groups fed semipurified diets containing CO or RHO as the only lipid source. Groups of 6 rats were fed ad libitum diets containing 5% or 15% vegetable oil during 15 or 60 days. Food intake was not dependent on the type of oil, and was higher in 15% oil diets (p < 0.01), increasing with time of feeding (p < 0.001). Bile flow was similar in all groups. Biliary concentrations of cholesterol, phospholipids and bile acids were affected by the time of feeding (p < 0.001). Plasma total and high density lipoprotein (HDL) cholesterol levels were higher in 15% oil fed rats (p < 0.05). Triglycerides concentrations were similar in all groups. The results indicate that oil concentration and time of feeding were the most important variables affecting the lipid composition of rats, independently of the fatty acid composition of the ingested fats. PMID- 8002699 TI - [Dietary determinants in cholesterolemia in an adolescent group]. AB - In view of the importance of cholesterol as a risk factor of cardiovascular disease, the present study analyzes the influence of the diet on blood cholesterol levels in a group of 156 teen-ager 14 to 18. The dietetic study pointed out the existence of diet cholesterol density higher than the recommended one of 100 mg/1000 Kcal, being the eggs, meat and the milk products the most important cholesterol food sources. No statistical correlations have been found between dietetic and blood data, though the feminine population, who has the highest cholesterolemia, has also the highest and unbalanced lipid intake when compared to men. The standing of this population seems not to be preoccupying, because the hipercholesterolemia data (all in the feminine population) are very few. PMID- 8002700 TI - [Preparation of flour processed with pigeon pea seed]. AB - Pigeon pea is a legume grain of good production capacity and of a relatively high nutritive value, which has not been used in Latin America on the basis of the potential it offers. In this study experiments were conducted to learn about the possibility of processing pigeon pea to yield an intermediate flour with good functional characteristics for food product development. The intermediate pigeon pea flour was produced through a selection of a process to efficiently dehull the grain followed by a thermic process to improve its functional properties and nutritive value. The best dehulling process was subjecting the grain to a vapor treatment for five minutes, followed by a 2-hour dehydration of surface moisture with air at 60 degrees and dehulling with an 8-disc dehuller for 10 minutes. Yield was 84% with 70.7% dehulling efficiency. Pigeon pea flours were prepared by three thermic processes: pressure cooking at 15 lb (121 degrees C) for 5 and 10 minutes as a reference product; cooking and drying with a drum dryer at 120 degrees C and 4 rpm and by extrusion-cooking with the material with 18 and 21% moisture at 270 and 300 degrees F, respectively. Process selection was based on the functional properties such as water absorption index, water solubility index, soluble nitrogen and viscosity, through chemical analysis of protein, available lysine and methionine and residual trypsin inhibitors, and through a biological evaluation of protein digestibility and quality. Both pressure cooking products had similar functional and chemical characteristics, however, the 5-minute cooked product has higher protein quality than the 10-minute product.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8002701 TI - [Possibility of using flour of pigeon pea in products prepared with rice or wheat flour]. AB - The present study reports on the development of foods containing processed pigeon pea (Cajanus cajan) flour. The pigeon pea flours described in a previous publication were prepared from dehulled pigeon peas by cooking in autoclave, by extrusion-cooking and by cooking/dehydration by drum-drying. Mixtures of cooked pigeon peas and rice were first evaluated biological through a protein complementation design using NPR. The results of this study showed that the two products had high protein quality and were similar when mixed in ratios of 80:20 to 40:60. For the evaluation of the processed pigeon pea flour, mixtures with rice (80:20) were used. All pigeon pea flours gave similar protein quality values. On the basis of these results three products were developed and tested. One was a gruel ("atole"), a second a fruit-flavored thick drink with and without 15% milk. Cookies were also prepared with a series of blends of pigeon pea flour (extrusion-cooked) and wheat. The gruel and the fruit flavored products had high acceptability based on a sensory evaluation test. Cookies with 100% pigeon pea flour were unacceptable, however, mixtures of 75% wheat flour and 25% pigeon pea flour gave cookies of attractive appearance and good taste. The study showed the possibility of preparing and utilizing tropical grain legume flours for food products of relatively high acceptability and nutritive value. PMID- 8002702 TI - [Improvement of protein quality of popped sorghum with soybean grain]. AB - The present study was carried out to evaluate the chemical composition and protein quality of popped sorghum by thermic dry processing. The chemical results indicated losses in the ether extract and increases in crude fiber. Likewise, losses were found in the essential amino acids, lysine and tryptophan, of 26 and 45%, respectively. The loss in these amino acids was confirmed by biological studies in which the protein quality of the raw sorghum, based on a PER was 32% of the casein value and of 8% for the popped sorghum (expanded). It was also found that the apparent and true digestibilities were lower for the popped sorghum than for the raw grain. In order to correct this loss in protein quality, the popped sorghum was supplemented with 5, 10 and 15% of roasted soybeans. Although no increase in quality was observed as evaluated by NPR, an increase in weight was found, as the soybean level in the diet was increased. This was attributed to the fact that the protein in the diet increased with respect to the soybean level. In an additional biological assay carried out with 15% of roasted soybean, a statistical significant increase in PER was found, equivalent to 74% of the casein value, while for the expanded sorghum without supplement, the relative casein value was of 30%. On the basis of these results an "alboroto" was formulated with 36% of popped sorghum, 10.5% whole roasted soybean, 3.5% dehulled sesame grain and 50% brown sugar. This product is superior to the commercial product in protein quality and quantity, as well as in energy content. PMID- 8002703 TI - [Development of a feeding formula from a protein concentrate of chick-pea (Cicer arietinum)]. AB - A medical formula was developed from a chick-pea (Cicer arietinum) protein concentrate obtained by ultrafiltration (67.8% of protein). Additionally sucrose, methionine, milk flavor, and mixtures of corn and coconut oils, vitamins and minerals were used, to perform FAO/WHO standards. All ingredients were blended in water to 50 degrees C, and the mixture was spray-dried with a Spray-drier using inlet and outlet air temperatures of 170 and 90 degrees C respectively. The nutritive value of the formula was evaluated with the Net Protein Ratio (NPR), Nitrogen Utilization (NU) and both relatives values to casein ANRC (R-NPR and R NU). The proximal analysis of the infant formula was: protein 16.0% (with 4.9 g/16 g N of reactive lysine), fat 25.8%, moisture 4.0%, ash 3.2% and carbohydrates 51.0%. The values of NPR, R-NPR, NU and R-NU were 3.95, 83.6, 3.55 and 82.5 respectively. This results shown the chick-pea protein concentrate, potencially utilizable as an ingredient in the formulas for medical purposes. PMID- 8002704 TI - [Quality evaluation of a dehydrated product based on potato (Solanum tuberosum), lupin (Lupinus mutabilis) and eggs]. AB - After a mathematical evaluation of 20 mixtures containing different proportions of potato (P), lupin (L) and whole egg (E) on dry basis and kept the latter component in a constant amount of 6 per cent, a mixture of 60:34:6 (P:L:E) was chosen for a further experimental work at a lab level because of his better nutritional value for the pre-school children feeding. When an eighteen percent suspension of the mixture mentioned above was dehydrated in a drum drier an adecuate yield of flakes was obtained with an appropriate water absorption. The sensory evaluation test of the dehydrated product as a sauce indicated a higher acceptance than purees. On the other hand, during a 90 days period storage test of the product as flakes, it did not show microbiological problems, although after 45 days rancidity appeared in the dehydrated product. PMID- 8002705 TI - [Influence of iron status on attention and intellectual performance of a population of Spanish adolescents]. AB - Dietetic, hematologic and biochemical data were used to asses the iron status of a group of 64 adolescents (37 males and 27 females), aged 15 to 18 (mean age 15.94 +/- 0.76 years), who study in a High School in the comunidad Autonoma de Madrid. All were asked to keep a dietary record during 5 days, one of which had to be a sunday. Iron intake was estimated using the Food Composition Tables of the Instituto de Nutricion (1990). The hematologic survey determined hemoglobin hematocrit mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC), serum iron and serum ferritin. These data were correlated with the scores obtained in the attention and school capability test (AT), that gave information about the verbal (V), reasoning (R) and calculus (C) capabilities. There is a positive correlation between MCV (r = 0.2705), MCH (r = 0.3370) ferritin (r = 0.3383) and attention. MCV (r = 0.2995), MCH (r = 0.3998), MCHC (r = 0.3134) and ferritin (r = 0.3970) were also correlated with the speed capability shown on the attention test and the hemoglobin level was correlated with the calculus capability (r = 0.2905). The students who obtained higher scores in the school capability test had also better blood parameter values. This was statistically significant for serum ferritin in males students and for hemoglobin and MCHC in female students. 19.6% of the adolescents had ferritin levels lower than 12 ng/ml. Their intelligence test scores were lower to those who had serum ferritin > or = 12 ng/ml.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8002706 TI - [Evolution of phenolic compounds and condensed tannins (Proanthocyanidins) during the development of bean seeds (Phaseolus vulgaris L.)]. AB - The evolution of phenolic compounds and tannins (proanthocyanidins) of bean seeds, Phaseolus vulgaris L., (cultivar aroana 80), from anthesis to maturity (10 to 45 days after anthesis), was investigated. During seed development, phenolic compounds and tannins contents increased by seed unit, until the 31st and 21st day after anthesis respectively, decreasing afterwards. The gradual decrease in catechin and the increase of its polymers (intermediate compounds), as well as the gradual increase in alpha-amylase inhibition capacity were indications that tannins polymerize during seed development. PMID- 8002707 TI - Insoluble dietary fiber of grain food legumes and protein digestibility. AB - The present work aimed to verify the digestibility of cooked whole food grain legumes. Samples of beans (Phaseolus vulgaris and Vigna sinensis), chickpeas (Cicer arietinum) and lentils (Lens culinaris) were used in the experiment. The interrelationship between the insoluble dietary fiber presented in the food grain legumes and the low protein digestibility was studied. The insoluble dietary fiber and the proteic nitrogen presented in the neutral detergent fiber (NDF) were determined. "In vivo" digestibility was performed in rats fed with diets containing cooked grain legumes, casein and protein free diet. The experiments were performed on rats over a period of 21 days. High excretion of nitrogen was observed by rats fed with cooked food grain legumes compared to casein diet. "In vitro" digestibility was performed by enzymatic hydrolysis with pepsin and trypsin. No significant differences was found between "in vivo" and "in vitro" digestibility. The heat treatment caused increased in the values of insoluble dietary fiber by the complexation of its components with protein and aminoacids. The results obtained showed the increased of the insoluble dietary fiber, in the cooked samples compared with raw samples. Significant values of protein nitrogen were found in the NDF, suggested that it was originated by complexation with proteins and aminoacids. This fact contributed to become proteic nitrogen nonavailability decreasing consequently the digestibility of the proteins. PMID- 8002708 TI - Preparation effects on tortilla mineral content in Guatemala. AB - We have previously reported that in Guatemala, the calcium, iron, and zinc contents of tortillas from rural areas are higher that that of tortillas from urban centers. This study examines variation in the calcium, iron, zinc and copper content of tortilla according to the implements used for making tortillas and inquires as to whether preparation effects mediate rural-urban variation in tortilla mineral content. Tortilla samples and information on how the tortillas were prepared were collected from the female heads of a total of 50 households from three rural, two semi-urban and one low income urban community. Samples of lime used for making tortillas were collected from 31 households. To grind masa, a hand mill was found to be used in some rural households whereas a motorized mill predominated in the semi-urban and urban areas. Most women used grinding stones called the "mano y metate" to further refine the texture of the masa. Tortillas prepared with the combined use of the hand mill and "mano y metate" had a significantly (p < 0.05) higher iron content. Use of the "mano y metate" was also associated with a significantly (p < 0.05) higher zinc content. These results suggest that the use of certain grinding implements may mediate rural urban variation in tortilla iron and zinc content. The cooking surface, pot used for nixtamalization, source of water, and amount of lime used did not significantly account for variation in the content of these minerals. PMID- 8002709 TI - Dietary fiber analysis of cassava using gravimetric methods. AB - We report the application of a method which combines digestion with pancreatin and neutral detergent treatment in the analytical study of dietary fiber from cassava. The use of pancreatin previous to the detergent extraction enabled rapid filtration, thus giving more reproducible results for neutral detergent fiber (NDF). Acid detergent fiber (ADF), hemicellulose, lignin and pectin were also determined. The values obtained for NDF (4.65%) and pectin (1.17%) are very important, considering their role in the digestive process. PMID- 8002710 TI - Specific protein phosphorylation induced in Xanthomonas campestris pv. oryzae by bacteriophage Xp12. AB - We have investigated the endogenous phosphorylation patterns of phosphorylated proteins of Xanthomonas campestris pv. oryzae induced by its bacteriophages. For bacteriophage Xp12-infected cells, at least three phosphoproteins with apparent molecular weights of 28, 28.5 and 45 kDa were detected by in vitro labeling with [gamma-32P]-ATP. These Xp12-specific phosphoproteins only occurred with Xp12 infection, and were not shown in uninfected or Xp10-infected cells. The protein kinase(s) responsible could use either ATP or GTP as the nucleotide substrate with nearly the same efficiency. Magnesium was proved to be an essential factor for the phosphorylation. EGTA treatment excluding the possibility that the presumed protein kinase was calcium-dependent. Under our reaction conditions, the optimal phosphorylation occurred at pH 7 to 8, for 30 to 40 min at 25 to 37 degrees C. The Xp12-specific protein phosphorylation hint the existence of a physiological regulation mechanism involved in the life cycle of bacteriophage Xp12. Furthermore, the presumed protein kinase was shown to be encoded by the genome of Xp12 rather than indirectly induced by Xp12 infection. PMID- 8002711 TI - The adaptive acid tolerance response in root nodule bacteria and Escherichia coli. AB - Root nodule bacteria and Escherichia coli show an adaptive acid tolerance response when grown under mildly acidic conditions. This is defined in terms of the rate of cell death upon exposure to acid shock at pH 3.0 and expressed in terms of a decimal reduction time, D. The D values varied with the strain and the pH of the culture medium. Early exponential phase cells of three strains of Rhizobium leguminosarum (WU95, 3001 and WSM710) had D values of 1, 6 and 5 min respectively when grown at pH 7.0; and D values of 5, 20 and 12 min respectively when grown at pH 5.0. Exponential phase cells of Rhizobium tropici UMR1899, Bradyrhizobium japonicum USDA110 and peanut Bradyhizobium sp. NC92 were more tolerant with D values of 31, 35 and 42 min when grown at pH 7.0; and 56, 86 and 68 min when grown at pH 5.0. Cells of E. coli UB1301 in early exponential phase at pH 7.0 had a D value of 16 min, whereas at pH 5.0 it was 76 min. Stationary phase cells of R. leguminosarum and E. coli were more tolerant (D values usually 2 to 5-fold higher) than those in exponential phase. Cells of R. leguminosarum bv. trifolii 3001 or E. coli UB1301 transferred from cultures at pH 7.0 to medium at pH 5.0 grew immediately and induced the acid tolerance response within one generation. This was prevented by the addition of chloramphenicol. Acid-adapted cells of Rhizobium leguminosarum bv. trifolii WU95 and 3001; or E. coli UB1301, M3503 and M3504 were as sensitive to UV light as those grown at neutral pH. PMID- 8002712 TI - Microbiological activities of nucleotide loop-modified analogues of vitamin B12. AB - Novel vitamin B12 analogues in which the D-ribose moiety of the nucleotide loop was replaced by an oligomethylene group and a trimethylene analogue containing imidazole instead of 5,6-dimethylbenzimidazole as well as cobinamide methyl phosphate were tested for biological activities with Escherichia coli 215, a B12- or methionine-auxotroph, and Lactobacillus leichmannii ATCC 7830 as test organisms. A cyano form of 5,6-dimethylbenzimidazolyl tetramethylene, trimethylene and hexamethylene analogues supported the growth of L. leichmannii in this order. 5,6-Dimethylbenzimidazolyl dimethylene and imidazolyl trimethylene analogues did not show B12 activity and behaved as weak B12 antagonists when added together with cyanocobalamin. An adenosyl form of the biologically active analogues served as coenzymes for ribonucleotide reductase of this bacterium, whereas that of the inactive analogues did not. The latter acted as weak competitive inhibitors against adenosylcobalamin. On the contrary, all the analogues did not support the growth of E. coli 215 at all by themselves and inhibited the growth when added with a suboptimum level of cyanocobalamin. A methyl form of the analogues also did not support the growth of E. coli 215, although they served as active coenzymes for methionine synthase of the bacterium. Since unlabeled analogues strongly inhibited the uptake of [3H]cyanocobalamin by this bacterium, it seems likely that the analogues exert their anti-B12 activity toward E. coli 215 by blocking the B12-transport system. PMID- 8002713 TI - Effect of the new fluorescent brightener Rylux BSU on morphology and biosynthesis of cell walls in Saccharomyces cerevisiae. AB - Rylux BSU, a new fluorescent brightener from the family of 4,4'-diaminostilbene 2,2'disulfonic acid derivatives, inhibited growth and cytokinesis of the yeast Saccharomyces cerevisiae. In the presence of 0.1-1 mg/ml Rylux BSU the cells grew in clumps, had irregular shape and were larger than controls. They formed apparently normal primary septa but their secondary septa and lateral cell walls, especially those in older cells, were abnormally thick with large deposits of amorphous wall material in the periplasmic spaces all over the cell surface. Chitin content in the cell walls of cells grown in the presence of Rylux BSU was increased 2 to 5 times in comparison to that of the controls and glucan content was reduced by up to 30%. In the in vitro assays with particulate membrane fractions, Rylux BSU acted as a non-competitive inhibitor of beta-1,3-glucan synthase with inhibitory constant Ki = 1.75 mg/ml whereas the chitin synthase was inhibited to a much lesser extent. From the difference of the effects of Rylux BSU on the synthesis of chitin in vivo and in vitro it is concluded that the brightener interacts with chitin synthase only indirectly, possibly by influencing the properties of integral plasma membrane. PMID- 8002714 TI - Activities and regulation of the enzymes involved in the first and the third steps of the aspartate biosynthetic pathway in Enterococcus faecium. AB - The enzymes aspartokinase and homoserine dehydrogenase catalyze the reaction at key branching points in the aspartate pathway of amino acid biosynthesis. Enterococcus faecium has been found to contain two distinct aspartokinases and a single homoserine dehydrogenase. Aspartokinase isozymes eluted on gel filtration chromatography at molecular weights greater than 250,000 and about 125,000. The molecular weight of homoserine dehydrogenase was determined to be 220,000. One aspartokinase isozyme was slightly inhibited by meso-diaminopimelic acid. Another aspartokinase was repressed and inhibited by lysine. Although the level of diaminopimelate-sensitive (DAPs) enzyme was not much affected by growth conditions, the activity of lysine-sensitive (Lyss) aspartokinase disappeared rapidly during the stationary phase and was depressed in rich media. The synthesis of homoserine dehydrogenase was controlled by threonine and methionine. Threonine also inhibited the specific activity of this enzyme. The regulatory properties of aspartokinase isozymes and homoserine dehydrogenase from E. faecium are discussed and compared with those from Bacillus subtilis. PMID- 8002715 TI - [Dual-energy X-ray absorptiometry in newborn infants]. PMID- 8002716 TI - [Detection and prevention of juvenile diabetes]. PMID- 8002717 TI - [Asthma in infants: a precise entity]. PMID- 8002718 TI - [Behcet disease in children in France]. AB - BACKGROUND: Behcet's disease is rare in children. The possibility of incomplete forms and the fact that the criteria for its diagnosis are not still agreed upon may explain why it could occur more frequently. POPULATION AND METHODS: A questionnaire was sent to all 362 French pediatric units. It requested data on possible sufferers from Behcet's disease, including EEG, CSF examination, brain CT scan, coloscopy, HLA groups, age at the first symptom and age at diagnosis. Among the 24 questionnaires concerning a possible case of Behcet's disease, 15 patients satisfied the international criteria for a diagnosis of Behcet's disease. RESULTS: These 15 patients (10 boys and 5 girls) were Caucasians (n = 9) or Africans (n = 6). The first symptoms were seen at 2 months to 14 years (mean: 10 yrs). The diagnosis was made between 7 and 18 years of age (mean: 11 yrs). HLA antigen B5 was identified in 7 patients and HLA-B12 in 1 patient. The first symptoms were oral ulcers (10 patients) plus skin lesions, genital ulcers and headache. All 15 patients suffered from oral ulcers, 8 from genital ulcers, 12 from skin lesions, 11 from arthritis, 9 from neurologic abnormalities, 6 from abdominal pain and 7 from eye inflammation; 10 patients had a complete form with ocular, neurologic and/or vascular abnormalities while 5 patients had an incomplete form with cutaneo-mucosal and/or GI and/or articular involvement. Two patients had family histories of Behcet's disease. CONCLUSIONS: Behcet's disease is not so exceptional in France. A better knowledge of its symptoms should result in its more frequent diagnosis in childhood. PMID- 8002719 TI - [Passive smoking in children. Its detection by the assay of urinary cotinine]. AB - BACKGROUND: Passive tobacco smoking is responsible for increased respiratory morbidity in young children. This point is not always understood by parents and the use of a sensitive marker for nicotine exposure may help them to smoke less. POPULATION AND METHODS: Urinary cotinine concentration was measured in 72 children, aged from 1 to 5 years, that had been admitted to our unit during October and November 1991 for various causes. The results were correlated with the smoking habits of their parents. Urine samples were obtained during the first hours after admission and the cotinine concentration was measured by HPLC. Concentrations > 5 micrograms per liter were considered to be positive. RESULTS: A total of 67 urine samples were analysed: 43 (64.2%) were positive with cotinine concentrations of 5 to 77 micrograms/l (mean: 19.7). Both parents of 21 children were smokers; the fathers of 18 children and the mothers of 11 children, alone, smoked. There was therefore at least one smoker in the environment of 50 children. There was a highly positive correlation between parental smoking and urinary cotinine (p < 0.0001). For the infants with only one parent who was a smoker, their urinary cotinine was higher when the smoker was the mother rather than the father. CONCLUSIONS: An urinary cotinine of > 6 micrograms per liter is a precise, sensitive, test for passive smoking in young children. This test is well accepted by families and its result may persuade parents to stop or moderate their use of tobacco. This test also could be used, as part of a pulmonary check up, as a public health indicator. PMID- 8002720 TI - [A retrospective survey on the respiratory course of severe bronchiolitis]. AB - BACKGROUND: Respiratory syncytial virus (RSV) infection in infancy can induce bronchial reactivity and virus-specific IgE production; these responses may favor the later development of asthma. This retrospective study examines the influences of early and severe forms of bronchiolitis on such an outcome. POPULATION AND METHODS: The files of 43 infants who had spent 1 to 24 days (mean 7.8 days) in intensive care between 1986-1990 for severe bronchiolitis with apnea and/or hypercapnia and/or hypoxemia were studied. The parents of all these children agreed to answer a standard questionnaire covering perinatal events, gestational age, number and frequency of recurrent episodes of wheezing, personal and familial history of allergy and environmental conditions. 15 of the children were preterm and 12 of them were given respiratory support during the neonatal period; 5 of these patients developed broncho-pulmonary dysplasia. RSV was isolated in 20 of 39 patients. RESULTS: 26 of the 41 surviving patients developed at least 3 episodes of wheezing over periods ranging from 5 to 54 months (mean 27.6 months): 15 of them were admitted at least once for asthma and 17 were given long-term bronchodilators and/or corticosteroids. Of the 8 patients with histories of allergy, 6 developed asthma, as did 7 of the 9 that had been in close contact with other children, and 9 of the 15 patients who had been exposed to tobacco. CONCLUSIONS: Not only is the development of asthma associated with risk factors (RSV infection, bronchopulmonary dysplasia, history of allergy, close contact with other children and exposure to tobacco) but the severity of the bronchiolitis per se is also correlated with this risk. PMID- 8002721 TI - [Pulmonary fibro-xanthogranuloma associated with renal amyloidosis in a 5-year old child]. AB - BACKGROUND: Pulmonary fibroxanthogranuloma is a benign tumor that is rarely seen in children. Its association with renal amyloidosis is not known. CASE REPORT: A 5 year-old boy developed arthritis in his wrists and his hands became clubbed. X rays showed a round mass in the left inferior pulmonary lobe. Sonography revealed that this mass contained fluid. Nephrotic syndrome appeared one month later. The pulmonary mass was then excised; histology indicated a fibroxanthogranuloma with no malignancy. Renal biopsy showed infiltration with amyloid substance. The nephrotic syndrome was improved one month after surgery, but contact with the child was then lost. CONCLUSION: The association of this tumor with apparently secondary amyloidosis may indicate that fibroxanthogranuloma is a pseudotumor of inflammatory origin. PMID- 8002722 TI - [Transient neonatal hyperthyroidism caused by transplacental transport of pituitary TSH receptor antibodies]. AB - BACKGROUND: Neonatal hyperthyroidism is a relatively rare condition. It can be severe and difficult to treat when the maternal hyperthyroidism has recently been recognized. CASE REPORT: A baby was born at 37 weeks of gestational age to a mother whose hyperthyroidism was only suspected at the 34th week. The mother was not given propylthiouracil until the day before delivery. At birth, the newborn presented with meconial fluid; it weighed 2,380 grams, was 46 cm long and had a head circumference of 32 cm. Clinical examination showed exophthalmos, tachycardia, hepatosplenomegaly, restlessness, moderate goiter and premature craniosynostosis. Laboratory data showed elevated serum free T4 (76 pmol/l), unmeasurable TSH, and the presence of thyroid-stimulating immunoglobulins. The infant was given propranolol (10 mg/day), and carbimazol (3.75 mg/day) from day 13. Clinical and biological improvement allowed the carbimazol to be stopped at 1 month. A relapse was treated with carbimazol plus L-thyroxine. Both drugs were discontinued at the age of 4 months. At 12 months, the baby is perfectly well and has developed normally. CONCLUSION: This transient thyrotoxicosis was due to the transplacental passage of TSH receptor antibodies. Its management was difficult because the mother was treated late during her pregnancy. PMID- 8002724 TI - [Total abnormal pulmonary venous return. Preoperative stabilization by extracorporeal veno-venous circulation]. AB - BACKGROUND: Total anomalous pulmonary venous return (TAPVR) is a rare congenital cardiac disease. When this includes pulmonary artery hypertension, the infant is severely ill. Survival beyond infancy is rare without surgical correction. CASE REPORT: A girl in whom hydramnios and a short femur were discovered by ultrasonography at the 25th week of gestation was admitted to the intensive care unit a few hours after birth because of respiratory distress. Blood PaO2 was 37 mmHg, PaCO2, 36 mmHg, and pH 7.25. She had tachycardia (190/min) and circulatory insufficiency. Echocardiography showed right ventricular overload, a right-to left shunt through a patent ductus arteriosus and foramen ovale and tricuspid insufficiency. This refractory hypoxemia was not corrected by conventional respiratory support, high-frequency oscillation plus dobutamine and dopamine followed by noradrenaline infusion. Because of further deterioration, the baby was given extracorporeal lung support; this rapidly improved the respiratory and hemodynamic conditions. Persistent pulmonary artery hypertension led to a second investigation that showed TAPVR She underwent emergency surgery. CONCLUSION: Extracorporeal lung support can stabilize a precarious state in a case of severe congenital cardiac disease, so allowing surgical treatment under satisfactory conditions. PMID- 8002723 TI - [Severe hypernatremic dehydration disclosing Netherton syndrome in the neonatal period]. AB - BACKGROUND: Netherton's syndrome is characterized by ichthyosis, trichorrhexis invaginata and other air shaft anomalies, and atopic diathesis. The ichthyosis is present at birth and can be complicated by hypernatremic dehydration. CASE REPORT: Adrien was the first child of non-consanguineous parents. His birth weight was 3,110 g. Ichthyosis was present at birth and the diagnosis of Netherton's syndrome was subsequently confirmed by skin biopsy. He was admitted to intensive care at the age of 4 days for a 20% loss of weight and dehydration. His blood chemistry was: Na+ = 192 mmol/l; K+ = 6.9 mmol/l; Cl- = 136 mmol/l; urea = 21 mmol/l; glucose = 12.1 mmol/l; creatinine = 209 mumol/l; hematocrit = 51%. Urinary analysis gave: Na+ = 113 mmol/l; K+ = 97 mmol/l; urea = 105 mmol/l. Progressive rehydration resulted in normal diuresis 24 hours later and a slow normalization of natremia to 138 mmol/l on day 10. Despite preventive i.v. phenobarbital, he developed convulsions on day 5 when his natremia was 177 mmol/l i.e. after a drop of 0.6 mmol/hour. The convulsions disappeared when he was given phenytoin and placed on respiratory support, but status epilepticus appeared on day 18 with normal natremia. This status epilepticus was not influenced by several antiepileptic drugs and was only cured when the patient was given tetracosactide followed by hydrocortisone plus sodium valproate. Adrien is now 3 years old and is neurologically and mentally normal. CONCLUSION: Hypernatremic dehydration can be a complication of neonatal ichthyosis; it may be severe with very high blood sodium concentration. Corticosteroids can be useful for treating persistent convulsions. PMID- 8002725 TI - [Kasabach-Merritt syndrome with pancreatic hemangioma in an infant]. AB - BACKGROUND: Kasabach-Merritt syndrome is characterized by one or more large hemangiomas associated with thrombocytopenia due to platelet trapping. The hemangiomas may be located in the abdominal viscera, in which case, treatment may be difficult. CASE REPORT: A 2 1/2 month-old boy was admitted because of the discovery of an abdominal mass. He was anemic (hemoglobin: 6.8 g%; reticulocytosis: 288,000/mm3), thrombocytopenic (50,000/mm3), hypofibrinogenemic (0.95 g/l), with fibrin split products in the blood. Ultrasonography showed that this mass was retroperitoneal and heterogeneous. X-rays delineated the mass, which distorted the duodenal loop and pressed forward against the stomach. Surgery showed that the mass included the pancreas, the root of mesenterium and the extrahepatic bile duct. This mass was biopsied. Histological examination showed infantile type hemangioendothelioma. Abdominal angiography showed that the mass was not very hypervascularized, and there were no dilated supplying blood vessels. An aortogram showed two other small vascularized areas. The patient was given methylprednisolone, but the volume of the mass remained unchanged, while hepatosplenomegaly and jaundice developed and ultrasound showed dilated extra- and intrahepatic biliary ducts. The patient was then given interferon alpha 2b for 1 month. Embolization of the small supplying arteries was performed because of a lack of improvement after 1 week of treatment. This procedure was followed by rapid disappearance of the signs of consumption coagulopathy, a progressive improvement in cholestasis, and decrease in the mass. CONCLUSION: Improvement in manifestations of this Kasabach-Merritt syndrome is difficult to assign to one of the several therapies. The rapid disappearance of consumption coagulopathy after arterial embolization suggests that this treatment was successful in our patient. PMID- 8002726 TI - [Protee syndrome associated with renal lithiasis and vesico-ureteral reflux]. AB - BACKGROUND: Proteus syndrome is characterized by a range of various manifestations. The main ones are partial gigantism of hands and feet, nevi, hemihypertrophy, macrocephaly. Urinary tract abnormalities are exceptional. CASE REPORT: A 6 year-old boy was examined because he had presented numerous abnormalities from birth. His weight was 26 kg (+3 SD) and his height was 135 cm (+4 SD). The main abnormalities were ptosis, pterygium colli, nevi of the cervical area, plagiocephaly, frontal bossing, scoliosis, hemihypertrophy involving the skin, mucosa and bones, macrodactyly, varicose veins and lipomatosis. He underwent surgery at the age of 3 years for urinary lithiasis associated with an ureterovesical reflux on the left side, i.e. the side of hemihypertrophy. CONCLUSION: This case suggests that Proteus syndrome may be an example of ectomesodermal dysembryoplasy but it requires confirmation by a report of at least one other case of obstruction of the ureteropelvic junction on the same side as hemihypertrophy. PMID- 8002727 TI - [Cerebral venous thrombosis disclosing Behcet disease]. AB - BACKGROUND: Behcet's disease is very occasionally revealed by thrombophlebitis in children. Dural sinus thrombosis can be one of its complication. CASE REPORT: A 14 year-old boy of Mediterranean origin was admitted for acute meningitis with temperature of 40 degrees C. His CSF contained 24 cells/ml and 0.33 g/l protein; it was sterile. The RBC sedimentation rate was 84 mm. Other investigations, including brain scan, were negative. The condition became worse, with a deterioration of visual acuity, attack of aphthous stomatitis and skin lesions at points of puncture. There was papilledema with retinal vascularitis. A second brain scan and MRI showed sagittal sinus thrombosis. The condition improved immediately after treatment with prednisolone and ticlopidine. The brain MRI taken 3 months later showed partial permeability of the sagittal sinus. The patient had several attacks of meningoencephalitis and stomatitis during the following 2 years. The last attack was complicated by iridocyclitis; this required cyclosporin treatment. CONCLUSION: Phlebothrombosis is a classic complication of Behcet's disease and can reveal the disease. Sagittal sinus thrombosis has never before been reported as the first manifestation of the disease in children. PMID- 8002728 TI - [Idiopathic eruptive macular pigmentation]. AB - BACKGROUND: Hyperpigmentation can be due to different cause or have no apparent cause. CASE REPORT: A 4 year-old boy was examined because pigmentation had appeared 5 months earlier. The cutaneous lesions were blue-grey, macular (diameter: 2-3 cm), with a predilection for the trunk, the lower part of the neck and the proximal part of the legs. There was no pruritus and the lesions did not urticate when rubbed. Histologically, there was epidermal acanthosis, moderate hyperkeratosis and dermal infiltration with numerous melanophages. The clinical lesions remained stable 6 months later. CONCLUSION: The cutaneous manifestations and their course are similar to those of idiopathic macular pigmentation usually reported in adolescents. Ultramicroscopic findings have led some authors to classify it as lichen planus. PMID- 8002729 TI - [Mycotic aneurysm of the iliac artery disclosed by an abdominal mass]. AB - BACKGROUND: Mycotic aneurysms are classic complications of infective endocarditis. Their diagnosis can be difficult when they are located in deep vessels. CASE REPORT: A 8 year-old boy was admitted for psoitis, tenderness of the left iliac fossa and a palpable mass. He was treated with antibiotics for 2 months for infective endocarditis, but vomiting and fever began after 3 weeks of therapy. Blood cultures showed Staphylococcus epidermidis. Ultrasonography of the mass showed findings compatible with an abscess but sampling of its contents showed blood. Immediate Doppler echography showed that the mass was an aneurysm of the left iliac artery. This diagnosis was confirmed by CT scan and aortography. The aneurysm was excised and a satisfactory repair was made using a Gore-tex graft. CONCLUSION: Although this mass had no clinical vascular characteristics, its origin should have been recognized because of the history of infective endocarditis and a better analysis of the ultrasonographic findings. PMID- 8002730 TI - [Radiological case of the month. Congenital pseudarthrosis of the ulna]. PMID- 8002731 TI - [Value of the fetopathological test in fetal medicine]. PMID- 8002732 TI - [Recent advances in pediatric ORL. Cochlear acoustic emissions]. PMID- 8002733 TI - [Pain in children. Current questions]. PMID- 8002735 TI - [Video-celio-surgery in children]. PMID- 8002734 TI - [A non-justified dogma: strict bed rest in rheumatoid purpura]. PMID- 8002736 TI - [Prevalence and clinical aspects of A and B subgroups of respiratory syncytial virus infection. Observation of 8 consecutive epidemics between 1982 and 1990]. AB - BACKGROUND: Infants suffering from respiratory syncytial virus (RSV) infection can have severe responses that require intensive care. This study compares the epidemiologic patterns and the severity of respiratory diseases produced by RSV strain subtypes A and B. POPULATION AND METHODS: The prevalence of RSV subgroups was studied over 8 consecutive outbreaks from 1982 to 1990. The files of 73 infants aged from 1 to 24 months admitted because of RSV infection between October 1987 and March 1990 were studied. The criteria of severity were tachypnea and/or the use of the accessory muscles for respiration, apnea and/or cyanosis, hospitalization for > 8 days, hypercapnia and/or acidosis, oxygen therapy, use of corticosteroids and/or bronchodilators, nutritional difficulties. RESULTS: A total of 374 RSV strains were isolated: 142 were group A and were 232 group B. Subtype A predominated during the winter 1987-1988 and subtype B during 1983 1984, 1984-1985 and 1989-1990. Some indicators of severity, such as degree of respiratory distress, duration of hospitalization and levels of oxygen saturation, were correlated with A subgroup infections, but the difference in the severity index for the two subtypes was not statistically significant. CONCLUSIONS: The results are not consistent with other previous reports, perhaps because different indicators of severity were used in this study and infants less than one month old or having other underlying diseases were excluded. PMID- 8002737 TI - [Emergence and development of competence in young children]. AB - BACKGROUND: The childhood emergence and development of motor behavioural skills is imperfectly understood despite intensive study. This report is of the development of motor skills and social behaviour in young children. POPULATION AND METHODS: 17 infants (9 boys and 8 girls) in good health, aged 8 to 11 months at the beginning of the research, were studied. They were observed in groups of 6 for 30 minutes, in a special area fitted out with climbing structures, once every two weeks for one year. Their movements and behavior were filmed. RESULTS: 1) Motor skills which allow the "conquest" of climbing structures and complex social behaviors (multimodal interactions, imitations, cooperations, anticipations of behaviors) had developed by the time the children were 12 months old and were first examined. 2) From 12 to 14-15 months old, they consolidated these motor skills and the frequency of imitations and multimodal interactions increased markedly. 3) From 14 to 18 months old, they assumed the standing position more and more during ascents and descents and the frequency and diversity of imitations and cooperations increased sharply. 4) There was relatively little aggressive behavior at all ages. CONCLUSIONS: Motor skills and social behavior appear earlier and are more complex in children moving freely among their peers in a special setting than previously reported for developmental scales. PMID- 8002738 TI - [Left ventricular involvement in mucoviscidosis after 2 years of age]. AB - BACKGROUND: The cardiac involvement in cystic fibrosis includes the rare cardiomyopathy seen in infants and changes in left ventricular performance in older children. POPULATION AND METHODS: 67 patients, 6 to 34 months-old (mean: 16.7), 37 male and 30 female, with cystic fibrosis, were studied. Their Shwachman score was < 70. None showed any clinical manifestations of left ventricular insufficiency, but 6 patients had right ventricular insufficiency. Echocardiography was performed on 58 patients; it showed dilation of the right ventricle in 32 of them. Left ventricular perfusion was studied with thallium 201 tomoscintigraphy and left ventricular ejection fraction with 99mTc ventriculography. RESULTS: The left ventricular ejection fraction was < 45% in 17 patients and scintigraphy showed hypofixation in 6 of them. In contrast, only 4 of the 50 patients with left ventricular ejection fraction > 45% had thallium hypofixation. CONCLUSIONS: Resting perfusion abnormalities are more frequent in patients with a low left ventricular ejection fraction. These perfusion abnormalities suggest that myocardial fibrosis complicates the advanced stages of cystic fibrosis. PMID- 8002739 TI - [Growth and endocrine function in major thalassemia]. AB - BACKGROUND: The risk of secondary endocrine dysfunction in patients with thalassemia major remains high, despite improvements in the care of hematologic problems. POPULATION AND METHODS: 31 patients (15 males, 16 females) with thalassemia major were studied. 28 of them had been regularly given blood transfusions since the age of 3.7 +/- 3.6 years. Iron chelation therapy had started before the age of 10 years in 9 patients, after this age in 15 patients; it was not performed or the time not specified in the 7 others. The mean dosage of deferoxamine was 20 +/- 6 mg/kg/day (9.6-34 mg/kg/day). Endocrine functions were evaluated at a mean age of 11.8 +/- 4.9 years and were monitored for 6.1 +/- 4.6 years (0 to 19 years). The hormones assay were: growth hormone (GH), thyroid, adrenal cortex, parathyroid and gonadal functions. RESULTS: The GH peak after stimulation was normal, but plasma somatomedin CIGFI was low and did not increase at puberty. 6 patients had peripheral hypothyroidism. Plasma cortisol was normal in the 16 patients examined, but plasma dehydroepiandrosterone sulfate was low in 24; this might be partly responsible for the delayed development of pubic hair. 2 patients aged 20 and 27 years was suffered from diabetes mellitus. Hypoparathyroidism occurred in 7 patients and 12 of the 24 patients with impuberism had a gonadotropin deficiency. The mean final height was -1.3 +/- 1.0 SD in boys (n = 7, mean age: 20 +/- 1 yr) and -1.3 +/- 0.9 SD in girls (n = 7; mean age: 19 +/- 1 yr), whether puberty was spontaneous or induced. CONCLUSIONS: The most frequent endocrine complications in these patients are delayed puberty because of gonadotropin deficiency, hypoparathyroidism and peripheral hypothyroidism. Substitution therapy, using sex steroids at an appropriate age, can induce the pubertal growth spurt. PMID- 8002740 TI - [Periventricular leukomalacia of late onset in a premature infant]. AB - BACKGROUND: Periventricular leukomalacia in preterm neonates is usually due to abnormal cerebral blood flow before and/or during delivery. It is diagnosed during the first month of life. This study describes a case of late-developing periventricular leukomalacia. CASE REPORT: A girl was delivered by cesarean section at the 23rd week of gestation that was complicated by placenta previa. She weighted 880 g and immediately required resuscitation. She did not develop respiratory distress syndrome. She was intubated and ventilated for the first two weeks of life and developed bronchopulmonary dysplasia requiring corticosteroid treatment. Extubation was possible on day 43. The neonate had been given antibiotics for the first 10 days of life and indomethacin on day 8 because of a patent ductus arteriosus. Repeated craniosonography showed moderate bilateral intraventricular hemorrhage and occipital areas of hyperechogenicity that disappeared at the end of the first month of life. Repeated electroencephalograms revealed no positive rolandic sharp waves until the infant was 42 days old. Craniosonography on day 48 showed areas of heterogeneous hyperechogenicity and NMR imaging showed bilateral frontoparietal leukomalacia with loss of white matter. The baby died on day 71. CONCLUSIONS: Late periventricular leukomalacia is exceptional and usually seen after postnatal abnormalities in cerebral blood flow and/or prolonged hypoxemia. Both these risk factors were absent in this patient. PMID- 8002741 TI - [Localizing of Langerhans islets adenoma by transhepatic portal catheterization]. AB - BACKGROUND: The procedures used to locate pancreatic endocrine tumors have only limited success in infants and children in whom the nodules may be small. Portal catheterization may therefore be useful. CASE REPORT: A child aged 6 yrs 4 months was admitted because of several recent episodes of pallor and sweating associated with hypoglycemia. Further investigation showed moderate hyperinsulinemia and low blood levels of ketone bodies and branched amino-acids after a 15 hr fast. Celiac angiography was normal. The hypoglycemic episodes recurred despite treatment with diazoxide for 6 months. A transparietal portal catheterization was therefore performed. Selective pancreatic venous sampling showed high concentrations of insulin in two small veins draining one part of the head of the pancreas (117 and 89 microU/ml). The head of pancreas was removed 16 months later. Extemporaneous examination revealed an adenoma 0.8 cm in diameter. This patient has completely recovered, 8 months after surgery. CONCLUSION: Transparietal portal catheterization can detect pancreatic areas with high insulin secretion. It may also help the interpretation of celiac angiographs in children, as diagnosis may be obscured by the normal rich vascularity of the pancreas in these patients. PMID- 8002742 TI - [Cerebral intraventricular and/or intraparenchymal hemorrhages in full-term newborn infants. Long-term outcome]. AB - BACKGROUND: Intraventricular and parenchymal hemorrhages are rare in full-term neonates. Their prognosis is still under discussion. POPULATION AND METHODS: 6 full-term newborns admitted between January 1985 and December 1988 developed intracranial hemorrhage: 3 had intraventricular hemorrhage and 3 parenchymal without intraventricular hemorrhage. The study includes the results of a questionnaire on the pregnancy and delivery, clinical, ultrasonographic and CT scan data. The long-term neuro-developmental outcome was assessed when the children were 4 to 7 year-old. RESULTS: All the patients were given phenobarbitone for 1 month to 1 year (one patient was given phenobarbitone plus phenytoin). One patient, aged 1 month, required insertion of a valve, because hydrocephalus developed. One patient had difficulties at school with developmental retardation; another patient developed minor difficulties. The 4 other patients had normal motor and mental development with good scholastic performances. CONCLUSIONS: The prognosis for intraventricular and parenchymal hemorrhage seems better in full-term than in pre-term infants. PMID- 8002743 TI - [Extensive fibrous endocarditis as first manifestation of systemic lupus erythematosus]. AB - BACKGROUND: Cardiac abnormalities, such as myocarditis, pericarditis or verrucous endocarditis (Libman-Sacks endocarditis) occur in about one third of patients with systemic lupus erythematosus. This study describes an unusual aspect of endocardial involvement. CASE REPORTS: Case no. 1: A 14 year-old girl was admitted 3 months after acute hemichorea because of heart failure plus biological inflammatory findings. Echocardiography showed mitral insufficiency with enlargement of the left atrium and ventricle. There was some infiltration involving the endocardium of the left ventricle, the chordae tendinae and the mitral valve. The titres of anti-DNA and anti-nuclear antibodies were elevated while the serum hemolytic complement was depressed. Skin biopsy showed IgG, IgM and C1q deposits along the dermoepidermal junction. Corticosteroids, diuretics and vasodilator drugs failed to completely cure the heart failure; the mitral insufficiency required mitral valve replacement 21 months later. Pathological examination showed extended fibrotic changes of the endocardium. Case no. 2: A 4 year-old boy was admitted for acute heart failure due to mitral insufficiency, associated with biological inflammatory findings. Echocardiography showed mitral insufficiency and enlarged left atrium and ventricle. Anti-DNA and anti-nuclear antibody titres were elevated. The patient was given antibiotics followed by corticosteroids and immunosuppressive drugs. The persistence of the mitral insufficiency required mitral valve replacement 7 months later. Pathological examination showed fibrotic changes of the endocardium. Exacerbation of the inflammatory process was seen 2 months after surgery, with development of diffuse proliferative lupus nephritis. The patient died of kidney failure and neurological complications, 44 months after cardiac surgery. CONCLUSION: In both patients, the systemic lupus erythematosus was revealed by endocardial involvement, a complication that is usually seen later. The endocardium changes responsible for mitral insufficiency and requiring valve replacement in these two cases were different from those described as verrucous endocarditis in classical forms of the disease. PMID- 8002744 TI - [Microangiopathic anemia following thrombopenic purpura]. AB - BACKGROUND: Chronic relapsing microangiopathic hemolytic anemia is rare in children. This report describes a case associated with thrombocytopenia following idiopathic thrombocytopenic purpura. CASE REPORT: A 4 year-old girl was admitted for acute idiopathic thrombocytopenic purpura (platelet count: 12,000/mm3) without anemia or fragmented red cells. The patient was given intravenous gammaglobulins without success, followed by prednisone (2 mg/kg/day). The platelet count was normalized, but decreased when the treatment was discontinued. The patient developed acute intracranial hypertension at the age of 5 yr 8 mo, following two cerebral hematomas. The platelet count was 9,000/mm3. A second course of intravenous gammaglobulins and prednisone was unsuccessful, so a splenectomy was performed. One year later, the patient was admitted because of diffuse purpura, anemia and jaundice. Hematologic findings were: Hb 8.4 g/dl, reticulocytes 448,200/mm3, fragmented red cells 16%, platelets 15,000/mm3, WBC 22,400/mm3. Seroimmunologic investigation showed a high titer of antinuclear antibodies. Examination for viral etiology was negative. Intravenous gammaglobulins had a transient effect on platelets, reticulocytes and fragmented red cells. The patient was then given vincristine plus prednisone; they were only effective when high doses were used. A second intracerebral hemorrhage occurred when the patient was given low doses of drugs. After 3 other hematologic relapses, the vincristine was stopped without further complication. CONCLUSION: The criteria for systemic lupus erythematous were not satisfied, despite the presence of antinuclear antibodies. A congenital deficiency of an unidentified plasma factor that reverses microangiopathic hemolysis and thrombocytopenia was not demonstrated in this patient, who could not be given fresh frozen plasma. PMID- 8002745 TI - [Cow's milk proteins intolerance disclosed by ulcero-necrotizing enterocolitis in a full-term infant]. AB - BACKGROUND: Necrotizing enterocolitis associated with milk protein intolerance is rare. CASE REPORT: A girl, born at term, weighing 3,150 g, was fed several different formulas because of persistent vomiting and diarrhea; some of these formulas contained cow's milk proteins. At 5 weeks of age, the patient developed acute abdominal distension and obstructive manifestations. Laparotomy showed intestinal distension and perforation of the distal small bowel, requiring resection with temporary ileostomy. Histological examination of the resected segment of the small bowel showed extensive necrosis of the mucosa and submucosa with involvement of the muscular layers. The patient was given parenteral nutrition for 3 weeks then refed with human milk. Cow's milk was introduced at the age of 2 1/2 months; this was immediately followed by vomiting and an anaphylactic reaction, with increased ileostomy fluid volume and blood and sugars in stools. A jejunal biopsy performed 3 weeks later showed moderate villous atrophy with a dense infiltrate of eosinophils below the epithelium. The RAST test was positive to beta-lactoglobulin and negative to casein and lactalbumin. The patient tolerated cow milk by the age of 18 months. CONCLUSIONS: Cow's milk protein tolerance should be evaluated when necrotizing enterocolitis occurs in the absence of classical risk factors. PMID- 8002746 TI - [Iron deficiency anemia is not always simple]. AB - BACKGROUND: Malabsorption of oraliron is rare, and more frequently suspected than proved. It could be due to prolonged iron deficiency. CASE REPORTS: Case no. 1: A boy was admitted at the age of 5 months for recurrent bronchitis. His hemoglobin was 8.2 g/dl, mean corpuscular volume (MCV) 60 micron3, mean corpuscular hemoglobin (MCH) 15 ng and mean corpuscular hemoglobin concentration (MCHC) 25 gHb/dl. The serum iron was 1 microgram/dl, iron binding capacity (IBC) was 284 micrograms/dl and ferritin was 14.9 ng/ml. Dietary iron was inadequate. The patient was given ferrous sulfate but iron deficiency persisted at the ages of 11 months and 3 years, probably due to poor compliance. Similar hematologic data (Hb: 6.4 g/dl, MCV 55 micrograms/m3, MCH 13.9 ng, MCHC 24 gHb/dl) were found at the age of 9 years. The patient was then given ferrous sulfate orally as test but the serum iron levels were unchanged during the 4 hours following ingestion. A parenteral iron preparation (iron-dextran, 500 mg) improved the hematologic data. 6 months later, a new oral test with ferrous sulfate improved the serum iron level. Case no. 2: A boy with complex congenital cardiopathy was operated on in the neonatal period and given oral iron at the age of 9 months because of anemia with microcytosis and hypochromia. This anemia was still present at 17 months and was associated with normal or high serum ferritin. Electrophoresis of hemoglobin was normal. At the age of 4 yr 5 mo, Hb was 9.7 g/dl, MCV 62.8 micrograms/m3, MCH 18.4 ng, iron 16 micrograms/dl and ferritin 94.1 ng/ml. An oral test with ferrous sulfate failed to increase the serum iron. The patient was then given parenteral iron-dextran without benefit, and a second oral test remained ineffective. After a second course of parenteral iron-dextran, Hb was 11.5 g/dl, MCV 74.1 micrograms/m3, MCH 23.7 ng while the serum iron remained low (23 micrograms/dl) and ferritin increased to 587 ng/ml. A third oral test with ferrous sulfate was still ineffective, as was a test using 4 mg/kg iron. CONCLUSION: The first patient suffered from iron malabsorption, presumably due to iron deficiency. The second patient could have abnormal metabolism and/or abnormal ferritin. PMID- 8002747 TI - [Iconographic rubric. A case of aneurysmal cyst of the fibula disclosed by injuries]. PMID- 8002748 TI - [Iconographic rubric. A case of acute pancreatitis caused by asparaginase]. PMID- 8002749 TI - [Chronobiology and its medical applications in children]. PMID- 8002750 TI - [Selenium in pediatric nutrition]. PMID- 8002751 TI - [Human recombinant erythropoietin and anemia in premature infants of parents who are Jehovah's Witnesses]. PMID- 8002752 TI - [Fatal anaphylactic shock caused by peanuts]. PMID- 8002753 TI - [Cholelithiasis in a child treated with ceftriaxone]. PMID- 8002754 TI - [Alpha-thalassemia/mental retardation syndrome related to the X chromosome]. PMID- 8002755 TI - [Treatment of cytomegalic inclusion disease with acyclovir and hyper-immune immunoglobulins in newborn infants]. PMID- 8002756 TI - [Apple peel small bowel syndrome and cystic fibrosis]. PMID- 8002757 TI - [Significance of a single umbilical artery at birth]. PMID- 8002758 TI - Predicting stroke inpatient rehabilitation outcome using a classification tree approach. AB - A classification tree, a nonparametric statistical analysis, was used to develop decision rules to predict a favorable inpatient stroke rehabilitation outcome. Descriptive and functional status data collected on admission from 225 patients were the predictor variables. Favorable outcome was defined as having met three criteria: discharged to community, survival greater than 3 months postdischarge, and no more than minimal physical assistance required in functional activities on discharge. The classification tree correctly classified 88% of the sample using only four of the predictor variables (level of independence in Toilet Management, Bladder Management, and Toilet Transfer, and adequacy of Financial Resources). The cross validation error rate was 18%. The advantages of the classification tree approach over parametric methods are that it is desirable for ordinal data, it readily identifies the interactions among predictor variables, the results are easily communicated, and it provides additional insights into the factors that predict outcome. PMID- 8002759 TI - Life satisfaction and well-being measures in ventilator assisted individuals with traumatic tetraplegia. AB - This study evaluates the effect of complete traumatic tetraplegia on the life satisfaction and well-being of 87 individuals, 42 of whom are ventilator supported, 2 years or more postinjury. Standard psychosocial instruments were used. The relative distress comparing ventilator dependence with loss of extremity function was also evaluated. The ventilator assisted individuals with tetraplegia (VAITs) were significantly more satisfied with their housing, family life, and employment when applicable, than were the autonomously breathing individuals with tetraplegia (ABITs). The VAITs' life satisfaction and other well being and quality of life indicators were generally positive, and were significantly underestimated by a control group of health care professionals. Only 23.8% of the VAITs expressed general dissatisfaction with their lives compared with 35.6% of the ABITs. The ABITs and the control group significantly overestimated the distress which the VAITs associated with ventilator use by comparison with loss of upper extremity function. We conclude that long-term life satisfaction and well-being are considered to be positive by the majority of both ABITs and VAITs, are at least as high in the latter as in the former, correlate best with family and social interaction, and are severely underestimated for both ABITs and VAITs by health care professionals. PMID- 8002760 TI - Factors associated with the quality of life of long-term spinal cord injured persons. AB - The purpose of this study was to identify issues associated with quality of life after spinal cord injury. The Life Situation Survey, a subjective indicator of life quality developed to address issues in chronic disability, served as the primary assessment tool. Data were collected during personal interviews of 100 persons with spinal cord injuries. Educational level, employment status, income, and a number of social activities were found to be associated with perceived life quality. Most notable was a finding that lower ratings of quality of life were associated with greater severity of disability, which was contrary to conclusions drawn from other studies. A plausible explanation for the inconsistency may lie in the different approaches and instruments used to measure quality of life. PMID- 8002761 TI - A client-computer interface for questionnaire data. AB - Our purpose was to assess efficiency and patient acceptance of a simple, inexpensive method of direct client-computer interface. A computerized version of the Sickness Impact Profile (SIP) was developed with the standard keyboard replaced by a numeric keypad. Forty-eight volunteer clients of an occupational rehabilitation center completed both the paper format and the computer format in randomized order, then were asked to compare the two methods in four areas. The majority of subjects rated the computer as easier to use and as the preferred method. Most subjects rated the computer and paper formats as equivalent in comfort and understanding. A summary score established that significantly more individuals preferred the computer format over the paper format (p = .02). Efficiency was determined by the mean time to score the test and produce a report (computer 39s, paper 309s). The correlation coefficients for the physical, psychosocial, and overall scores were very acceptable being greater than 0.90. These data indicate that a simple client-computer interface for the SIP is preferred by clients and is more efficient compared to the paper and pencil format. PMID- 8002762 TI - The relationship between cognition and functional independence in adults with traumatic brain injury. AB - This study investigates the relationship between cognitive impairment, as measured by Orientation Group Monitoring System (OGMS) scores, and disability as measured by Functional Independence Measure (FIM) scores in a sample of 122 persons with traumatic brain injury admitted to an inpatient rehabilitation unit. The relationships between Aggregate OGMS and FIM Total, FIM Motor, and FIM Cognitive scores were significant (rho = .49, p < .001; .40, p < .001; and .64 p < .001 respectively). Lower cognition was related to greater disability; with this relationship stronger for FIM Cognitive versus FIM Motor scores. Consistent with prior research, time to rehabilitation was significantly related to FIM Total (rho = -.42 p < .001) at admission to rehabilitation, with shorter time to rehabilitation related to greater functional independence. Stepwise regression indicated that the Aggregate OGMS score contributed 24%, and time to rehabilitation 5% unique variance to FIM Total score. These results support previous findings of distinct cognitive and motor subscales of the FIM, and suggest the importance of cognitive impairment to both. PMID- 8002763 TI - Physical activity program for older persons: effect on balance, strength, neuromuscular control, and reaction time. AB - Regular exercise has been recommended to improve balance, strength, and coordination in older persons. In this study, 44 persons, aged 50 to 75 years (mean 62.4 yrs) underwent assessments of quadriceps strength, reaction time, neuromuscular control, and body sway on two occasions before beginning a 10-week exercise program. The subjects were retested for the same measures at the end of the program. The mean number of classes attended for the 40 subjects who were retested was 16.2 (range 11 to 19). On completion of the program, the subjects showed improved performance in the tests of quadriceps strength, reaction time, body sway on a firm surface with the eyes closed, and a compliant surface with the eyes open and closed. In contrast, a group of nonexercisers showed no improvements in any of the test measures. These results suggest that exercise may play a role in improving a number of sensorimotor systems that contribute to stability in older persons. PMID- 8002764 TI - Variant and invariant characteristics of the sit-to-stand task in healthy elderly adults. AB - The purpose of this study was to identify kinetic, kinematic, and electromyographic (EMG) characteristics during sit-to-stand (STS) in healthy elderly subjects that were affected by changes in movement speed or initial starting position. Eight healthy elderly adults performed the STS movement at natural and fast speeds. Their ankles were placed in either 5 degrees or 18 degrees of dorsiflexion prior to the movement. A motion analysis system, single force plate, and EMG equipment were used to collect data on ankle, knee, and hip movement, vertical ground reaction forces, vertical and horizontal velocity of the head, and EMG activity from selected muscles. The data were further described according to three specific phases of the STS movement. Two-way analyses of variance for repeated measures were used to determine which of the kinematic, kinetic, and timing variables were affected by changing the speed of the movement or the initial ankle position. When asked to stand as fast as possible, muscle onsets and movement phases were shortened. However, when expressed as a percent of total movement time, normalized extensor muscle onsets were found to be earlier during fast movement of the task, whereas the other variables were not different. Changing the initial ankle position affected muscle onsets, duration of movement phases, and joint excursion. We conclude from these data that many of the characteristics of the sit-to-stand movement are speed invariant and therefore the STS movement is for the most part programmed.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8002765 TI - Dynamic neck strength training effect on pain and function. AB - This study examined whether neck resistance training could increase strength and reduce pain in workers with a high prevalence of neck disorders. Middle-aged women workers (n = 17) exercised twice weekly for 8 weeks. Each session (12min) consisted of three sets of 12 repetitions of resisted rotation, flexion, and extension muscles using hydraulic dampers. Resistance was set individually and progressively increased every second week. Angle-specific maximal isometric rotator, extensor, and flexor torque was measured before and after training. Torque during rotation, flexion and extension increased (p < .05) on average 35%, 27%, and 19%, respectively, after training. Perceived pain, assessed using a four graded scale, was reduced (p < .05) after training. It is suggested that 12 minutes of specific neck strength training twice weekly for 8 weeks increases strength of rotator, extensor, and flexor muscles of the neck. Also all individuals who had pain reported reduced perceived neck pain after training. PMID- 8002766 TI - Psychopathology and the rehabilitation of patients with chronic low back pain disability. AB - Recent research has clearly demonstrated the important role that psychopathology and other psychosocial factors can play in chronic low back pain disability (CLBPD). The purpose of this study was to evaluate whether diagnosed psychopathology is a significant limiting factor in the successful rehabilitation of patients with CLBPD. One hundred fifty-two CLBPD patients (97 men, 55 women) were given a structured psychiatric interview for official DSM-III-R diagnosis of psychopathology upon entering an intensive 3-week functional restoration treatment program. All patients were assessed for the presence of Axis I clinical disorders and Axis II personality disorders. They were subsequently tracked for 1 year after program completion, with treatment outcome being defined as return-to work status at this 1-year time period. Results demonstrated that, though more than 90% of patients obtained at least one Axis I diagnosis, and more than 50% obtained at least one Axis II diagnosis, neither type nor degree of psychopathology were significantly predictive of a patient's ability to successfully return to work. These prospective study results suggest that if a treatment program is structured to appropriately manage psychopathology, as is the case of an intensive functional restoration program, then psychopathology does not have to interfere with successful treatment outcome. PMID- 8002767 TI - Information effect on the perception of pain during electromyography. AB - Pain during the performance of electromyography (EMG) is an important clinical problem because pain distresses the patient and can interfere with diagnostic accuracy. We hypothesized that anxiety and pain perception associated with EMG would decrease if patients received written material describing the EMG before examination. Forty-two subjects received written material and 30 did not. Information before the test significantly decreased pain perception for women during the nerve conduction studies (p = .008), but not during the needle examination. A similar effect was not identified for the men. Other results indicate that women perceive the test as more painful than do men, older subjects perceive more pain and experience greater anxiety than do younger subjects, and all subjects perceive greater pain during the performance of (concentric, bipolar) needle electromyography than during the nerve conduction studies. PMID- 8002768 TI - The effect of participating in a functional electrical stimulation exercise program on affect in people with spinal cord injuries. AB - Functional electrical stimulation (FES) is a technology that is increasingly being used in the acute and post rehabilitation of people with spinal cord injuries. Though there has been considerable interest in the potential psychological effects of FES, little research has been done in this area. This study examined the effect of participation in an FES exercise program on affect in 37 persons with spinal cord injury. The effect of the subjects' expectations is also examined. Results indicate significant changes in negative affective status but no significant changes in positive affect. In particular, the results show increases in depression and hostility in subjects in the treatment group who had unrealistic expectations for the FES program. It is important to identify and monitor FES participants who have unrealistic expectations. PMID- 8002769 TI - Functional electrical stimulation treatment of postradiculopathy associated muscle weakness. AB - Eighteen chronic pain patients (CPPs) with postradiculopathy-associated muscle weakness were entered into a nonrandomized functional electrical stimulation (FES) clinical treatment study to determine if FES can improve postradiculopathy associated muscle weakness. Because of the clinical nature of the unit, the CPPs could not be denied treatments other than FES. To control for these other treatments, the CPPs were used as their own controls with two control conditions, ie, where possible, the contralateral probable normal muscle was used as a control (control 1) and; in a subgroup of CPPs (n = 6), FES treatment was initially withheld to the probable weak muscle (control 2). Strength was measured as isometric maximum voluntary contraction (IMVC) and was used as the outcome treatment variable. IMVC was measured in both the probable weak and contralateral probable normal muscles at entrance into the Pain Center, at beginning of FES treatment, at completion of FES treatment, and for the control 2 condition at the end of the non-FES treatment period. Statistical analyses of the IMVC strength results using the two control conditions indicated (1) both the FES-treated and untreated muscles increased significantly in IMVC strength, (2) improvement in IMVC strength for FES-treated muscles was significantly greater than for probable normal FES-untreated muscles and, (3) improvement in IMVC strength in FES-treated muscles was significantly greater during the FES-treatment period than during the non-FES treatment period. FES treatment of postradiculopathy-associated muscle weakness in CPPs seems to increase the strength of the probable weak muscle above the increase in strength provided by other concurrent treatments.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8002770 TI - Reliability of the maximal aerobic power and ventilatory threshold in adults with cerebral palsy. AB - This study examines the test-retest reliability of the ventilatory threshold (VT) and the maximum oxygen uptake (VO2max) in adults with cerebral palsy (CP). Nine subjects completed two continuous incremental tests on either a wheelchair ergometer (WE, n = 5) or a cycle ergometer (CE, n = 4) to volitional fatigue. Metabolic and cardiorespiratory responses were continuously monitored during the tests with an automated metabolic cart interfaced with an electrocardiogram. Two experienced evaluators identified the VT using standardized respiratory gas exchange criteria. The reliability coefficient for the VO2max during the two trials was significant (r = 0.83, p < .05). However, there was no significant relationship (p > .05) between the two trials for the oxygen uptake (VO2) at the VT identified by the two evaluators (r = 0.45 and 0.43). The correlations for this variable between the two evaluators were highly significant on each trial (r = 0.99 and 1.00, p < .01). No significant differences were observed between the two trials for the VO2 at the VT and the VO2max. These results suggest that when monitoring the cardiorespiratory fitness of adults with CP, it may be more appropriate to evaluate the VO2max rather than the VT, because the former variable can be reliably determined in these individuals whereas the latter lacks consistency. PMID- 8002771 TI - Intermittent digital cyanosis as the sole presenting sign of pulmonary embolus: an unusual case report. AB - A 77-year-old man who was undergoing comprehensive rehabilitation for a right subcapital femoral neck fracture presented with intermittent digital cyanosis of 3 days duration. He had no other cardiopulmonary signs or symptoms, therefore a diagnosis of Raynaud's Phenomenon was considered but ruled out because of no prior history of similar episodes or associated conditions. A ventilation perfusion (V/Q) scan was obtained and was highly indicative of pulmonary embolus. Dopplers and impedance plethysmography (IPG) revealed a left lower extremity deep vein thrombosis. Heparinization resulted in cessation of the cyanotic episodes. Intermittent digital cyanosis as the sole presentation of pulmonary embolus has not been previously reported in humans. Pulmonary embolus is notoriously difficult to diagnose based on clinical signs and symptoms. Intermittent peripheral cyanosis should raise the index of suspicion for the possibility of pulmonary embolus. PMID- 8002772 TI - Late onset of syringomyelia after traumatic brain injury: association with Chiari 1 malformation. AB - Syringomyelia should be suspected when progressive weakness or sensory loss develops. It most commonly occurs as a congenital malformation but has also been associated with spinal cord injury and the Chiari malformation. Symptomatic Chiari malformation after head injury is rare and usually presents with signs of acutely increased intracranial pressure. This article describes syringomyelia as a late onset complication of head injury in the presence of an underlying Chiari malformation. A possible causal relationship between head injury, the brain malformation, and an extensive syrinx is postulated. PMID- 8002774 TI - The geometry of the psoas muscle as determined by magnetic resonance imaging. AB - Magnetic resonance images from fifteen physically active and asymptomatic male volunteers were collected to present morphometric parameters on the psoas and its moment arms, which are important in the study of spinal mechanics and models for the investigation of low back pain. The mean age of the subjects was 21.5 +/- 1.8 years. Data were obtained from nine vertebral and/or intervertebral levels (L2, L2/L3, L3, L3/L4, L4, L4/L5, L5, L5/S1, S1). In general, the psoas increased in size as it descended the trunk, moving anteriorly and slightly laterally in relation to the vertebral column. Maximum cross-sectional areas for the psoas (M = 16.3cm2) were observed at the L4/L5 level. Right-left symmetry was apparent in the aforementioned dimension, but not with respect to the mediolateral (X) diameter of the muscle. The length of the X moment arm was significantly (p < .05) greater for the right versus the left psoas from L3 to S1, with the length increasing as the psoas descended the trunk. However, this trend was not noted for the anteroposterior (Y) moment arm where observed values remained relatively small throughout the course of the muscle. These results will contribute to the study of low back pain onset and the design of appropriate rehabilitation interventions by providing accurate morphometric parameters for biomechanical models to predict of the loading conditions of the spine in vivo. PMID- 8002773 TI - Chronic ventilator use in osteogenesis imperfecta congenita with basilar impression: a case report. AB - Osteogenesis imperfecta, a rare connective tissue disorder, is known to be associated sometimes with the invagination of the basilar skull. This deformity may disturb respiratory function secondary to brain stem compression and hydrocephalus. In addition, the deformed thoracic cage and fragile ribs make pulmonary care more complicated. A case of 24-year-old man is presented with brain stem compression syndrome secondary to osteogenesis imperfecta congenita with basilar impression. He developed respiratory failure and became tracheostomy positive-pressure ventilator dependent at the age of 21 years. He also suffered multiple skeletal abnormalities and mental retardation, and following the brain stem compression, severe quadriparesis. The patient's condition is stable since he has been using the ventilator and he is currently living in the community. PMID- 8002775 TI - A self-controllable mask with helmet to prevent self finger-mutilation in the Lesch-Nyhan syndrome. AB - Self-mutilation is a characteristic symptom of Lesch-Nyhan syndrome. We report a newly developed orthosis for managing self-mutilation of the fingers through biting. The orthosis has a plastic mask attached to a helmet; the patient can manage the mask with one hand to stop biting fingers on the other hand. This is a report of a 6-year-old boy who was able to control finger biting by using the orthosis. Eighteen months later he has stopped biting his fingers and no longer wears the orthosis. PMID- 8002776 TI - Detection of visual field deficits and visual neglect with computerized light emitting diodes. AB - A computer test for visual field deficits and visual neglect was developed and evaluated by testing 63 patients with brain damage. This computer test controls the sequence of unilateral or bilateral lights series, and stores the responses. Test results are compared to clinical and ophthalmological tests and neuropsychological assessment. Visual field deficits were present in 17 patients on the computerized test, in 16 patients on ophthalmological test, and in 13 patients on clinical examination. Neglect was present in 12 patients on the computerized test, and in 10 patients on the neuropsychological assessment. Eighteen patients had mixed disorder (hemianopia and neglect). Results of the chi 2 statistic confirm the greatest correlation between the computerized test and the ophthalmological (phi = 0.93; p < 0.001) and neuropsychological (phi = 0.90; p < 0.001) tests. Correlation between the computerized test and the clinical examination was poorer (phi = 0.85; p < 0.001). The computerized test makes it possible to detect mixed disorder with the same tool, during the same examination. PMID- 8002777 TI - ACRM supports CCD statement on healthcare reform. American Congress of Rehabilitation Medicine. PMID- 8002778 TI - Detection of bluetongue virus in the blood of inoculated calves: comparison of virus isolation, PCR assay, and in vitro feeding of Culicoides variipennis. AB - The interval after infection when bluetongue virus (BTV) was present in the blood of calves inoculated with BTV serotype 10 (BTV 10) was evaluated by virus isolation (VI) in embryonated chicken eggs (ECE), BTV-specific polymerase chain reaction (PCR), and in vitro blood feeding of vector Culicoides variipennis (C.v.) sonorensis. BTV nucleic acid was detected by PCR in blood cells for 16 to 20 weeks after infection whereas infectious virus was detected by VI in ECE for 2 to 8 weeks. BTV was detected in calf blood by in vitro feeding of C.v. sonorensis for only 0 to 2 weeks after inoculation of calves with BTV 10. Selected bloods which were positive by PCR analysis but not by VI in ECE were not infectious for sheep. The data are consistent with the hypothesis that prolonged viremia in BTV infected cattle results from association of the virus with blood cells, especially erythrocytes. The fact that calf blood that contained viral nucleic acid as determined by PCR analysis, but not infectious virus as determined by VI in ECE, was not infectious for either the insect vector or sheep suggests that cattle whose blood contains BTV nucleic acid but not infectious virus are unimportant to the epidemiology of BTV infection. PMID- 8002779 TI - Generation of multiple drug resistance by sequential in vitro passage of the human immunodeficiency virus type 1. AB - We have sequentially passaged both laboratory and clinical isolates of the human immunodeficiency virus type 1 (HIV-1) in MT-4 cells in the presence of increasing concentrations of different drugs to derive viral variants that are multiply resistant to various combinations of ddC, ddI, d4T and AZT. The EC50 values obtained for the viruses thus generated varied between 50-100 times above those of parental wild-type strains in the case of AZT, 20-30 times for d4T, but only 10-15 times for ddI and ddC. Cultivation of AZT-resistant viruses in the presence of increasing concentrations of ddI yielded viruses that were resistant to the latter compound, with no apparent decrease in susceptibility to AZT. Sometimes, viruses selected for resistance against ddI were cross-resistant as well against ddC, although most viruses selected for resistance to ddC were not cross resistant to ddI. Combinations of two or three of these compounds inhibited replication of HIV variants that displayed resistance to the same drugs when tested individually. No emergence of drug resistance was demonstrable when combinations of drugs were employed simultaneously in these selection protocols or when single drugs were used in concert with interferon-2 alpha or high dilutions of virus-neutralizing antisera. Cloning and sequencing of some viruses resistant to each of AZT, ddI, and ddC revealed the simultaneous presence of mutations at sites 41, 74, 184 and 215 within the HIV pol gene open reading frame. PMID- 8002780 TI - Immunogenicity of non-structural proteins of foot-and-mouth disease virus: differences between infected and vaccinated swine. AB - Non-structural as well as VP1 recombinant proteins of foot-and-mouth disease virus (FMDV) produced in E. coli, have been used to study the specific antibody response of infected or vaccinated swine. An analysis of sera from infected pigs, using a direct ELISA, showed that polypeptide 3ABC (spanning non-structural proteins 3A, 3B and 3C) was the most antigenic among the recombinant proteins studied and allowed specific detection of FMDV infected swine from the second week after the infection. The sensitivity of this assay was comparable to that obtained when the whole FMDV was used as ELISA antigen. Conversely, use of polypeptide 3ABC did not allow detection of significant levels of antibodies in sera from vaccinated animals. This differential pattern of ELISA reactivities offers a promising approach for the distinction of infected from vaccinated pigs. In addition, a highly specific and sensitive method of diagnosis for FMDV replication was achieved using an immunoblotting assay which detected antibodies against the 3ABC polypeptide. PMID- 8002781 TI - Subgrouping of respiratory syncytial virus strains from Australia and Papua New Guinea by biological and antigenic characteristics. AB - Strains of respiratory syncytial virus from 3 major areas of Australia and Papua New Guinea (PNG) were analyzed for variations in their antigenic and biological properties and in the molecular weights of their major structural proteins. Seventy-eight strains from infants and young children with LRI were collected from 1981-1984. The RSV season in the Australian cities lasted from April through September, with major peaks in July of each year, while the RSV season in tropical PNG was year-round, with small peaks in March and October of each year coinciding with excessive rainfall. Fifty-six strains were analyzed in detail; 40 were typed by time-resolved fluoroimmunoassay with monoclonal antibodies as group A strains and 16 were group B; both groups were concurrent. Three children of one family had sequential RSV infections 13 months apart, and the etiologic group A strain was identical both years in terms of growth and antigenic properties with strain-specific ferret antisera; the second infection was milder in all three children. On average, the group A strains replicated considerably better than group B strains in HEp2 cells, producing 53% more syncytia and 99% higher infectious virus titers in 31% less time in culture. Ten group A and B reference strains exhibited the same growth patterns as the A and B regional strains, respectively. Differences in antigenicity as measured with hyperimmune antisera to prototype Long strain were even greater. Group A strains exhibited a mean 68% greater IFA staining than B strains, a 71% greater EIA reaction, and were neutralized to 69% higher serum titers than B strains. Again, the reference A and B strains included as controls gave patterns identical to those of the regional strains. Finally, the P phosphoprotein had consistently higher molecular weight in A strains (mean 35,900) than B strains (mean 33,100). Small variations in the sizes of the F and G glycoproteins were not sufficient to suggest grouping on this basis. PMID- 8002782 TI - Pseudorabies virus infectivity for swine skin characterized in vitro. AB - The infectivity of pseudorabies virus (PrV) was demonstrated in a cell substrate derived from swine skin explant cultures designated primary porcine skin cells (c/cSLA PPSC). c/cSLA PPSC infected with either wild type or TK- PrV strain Kaplan (Ka) developed typical cytopathologic changes (CPE) as early as 4 h post inoculation (p.i.). The CPE caused by PrV on c/cSLA PPSC was specifically neutralized by covalescent swine sera. Synthesis of late viral proteins was demonstrated in PrV-infected c/cSLA PPSC by indirect fluorescent antibody staining using monoclonal antibodies (mAbs) specific for PrV gIII. PrV induced protein synthesis was further confirmed by specific immunoprecipitation of 35S methionine labeled viral polypeptides from PrV-infected c/cSLA PPSC with PrV convalescent swine serum, PrV immune mouse serum or mAb to PrV gIII. Moreover, the virus progeny derived from c/cSLA PPSC was shown to be infectious for MDBK cells and this infection was specifically neutralized by PrV convalescent swine serum. The capacity c/cSLA PPSC to support a complete growth cycle of PrV and the relative ease of deriving these cells from pigs can be applied in an autologous fashion in studies of cellular immunity where the MHC needs to be matched. PMID- 8002783 TI - A 79 amino acid oncogene is responsible for human cytomegalovirus mtrII induced malignant transformation. AB - Human cytomegalovirus (HCMV) morphological transforming region (mtr)II is the only HCMV mtr that was retained and expressed in transformed mouse or rat cells. The minimal transforming region has previously been shown to be within a 980-bp BanII/XhoI subfragment which encodes three open reading frames (ORF) of 34, 79, and 83 amino acids. This report provides definitive evidence that the 79-aa ORF is responsible for mtrII mediated tumorigenic transformation. The 79-aa ORF, subcloned into a mammalian expression vector, pCHC79orf, induced morphologic transformation of NIH 3T3 cells. These transformed cells expressed 79-aa ORF specific transcripts and were tumorigenic when injected into nude mice. A construct containing a triple termination linker inserted after codon 24 failed to transform NIH 3T3 cells to tumorigenicity even though 79-aa ORF specific transcripts were expressed. Furthermore, when the triple termination linker was inserted after codon 49, tumorigenic transformation still occurred. These results demonstrate that the 79-aa ORF is the oncogene within HCMV mtrII and that the first 49-aa are sufficient. PMID- 8002784 TI - Evidence for a multistep mechanism for cell-cell fusion by herpes simplex virus with mutations in the syn 3 locus using heparin derivatives during fusion from within. AB - Addition of heparin-Na+ as well as related substances of high and intermediate MW (Arteparon and polyanion SP54) 3 h after infection inhibit fusion from within (FFWI) induced by HSV strains with mutations in the syn 3 locus only. The concentration of heparin-Na+ required to inhibit FFWI is 10-fold higher (1 mg/ml) than that needed to inhibit adsorption. Instead of fusion, cell rounding is observed. The effect is readily reversible. A low MW heparin disaccharide is ineffective. Neomycin, at a concentration of 8 mM, inhibits FFWI induced by all HSV-1 but not HSV-2 strains, whereas adsorption is inhibited at 3 mM. We conclude from our observations that cell-cell fusion (FFWI) induced by syn 3 locus mutants of HSV-1 depends on a multistep mechanism. One may be constituted by pre-existing cell-cell connections or microfusions leading to cell rounding, whereas another may be active using newly appearing cell bridges during FFWI; also the three dimensional structure of the cell membrane may be of importance. Moreover, the molecular mechanisms of FFWI induced by mutations in the syn 3 locus compared to the other 5 syn loci should be different. PMID- 8002785 TI - Human herpesvirus 6 and human herpesvirus 7 infections in renal transplant recipients and healthy adults in Turkey. AB - We explored the prevalence of human herpesvirus 6 (HHV-6) and human herpesvirus 7 (HHV-7) infections in 16 renal transplant recipients and 16 healthy controls by virus isolation, serology, polymerase chain reaction (PCR) followed by dot blot hybridization. HHV-6 variant A was isolated from one renal transplant recipient. Seven patients (44%) and six controls (38%) had HHV-6 variant B DNA in their peripheral blood mononuclear cells. The prevalence of HHV-7 DNA was found to be the same in patients and controls (19%). PMID- 8002786 TI - Early interaction of feline calicivirus with cells in culture. AB - The kinetics and biochemical properties of feline calicivirus (FCV) attachment to Crandell-Reese feline kidney cells were determined. Maximum binding was observed at pH 6.5. Cells in suspension at 4 degrees C bound virus more efficiently than cells in monolayers at 4 degrees C or 37 degrees C. High initial binding rate was observed in monolayers or cells in suspension and proceeded to a maximum at 90 min, although half maximal binding was observed as early as 15 min. Binding was specific and competitively blocked by serotypically homologous or heterologous FCV as well as by San Miguel sea lion virus. Treatment of cells with proteases increased FCV binding, whereas phospholipase had no effect on virus attachment. Conversely, cells treated with neuraminidase followed by O-glycanase treatment showed a decreased binding ability. Cells of feline origin bound FCV very efficiently, and non-permissive cells showed a poor binding ability. Following transfection of viral RNA, infectious virus could be recovered from all non permissive cells, except from Madin-Darby canine kidney cells. These results suggest that FCV binds to a receptor in which carbohydrates may be an important component and that FCV replication in non-permissive cells is primarily restricted by the absence of appropriate receptors on the cell surface. PMID- 8002787 TI - Polymerase chain reaction amplification of latent Aujeszky's disease virus in dexamethasone treated pigs. AB - A polymerase chain reaction (PCR) amplification assay was developed for the detection of Aujeszky's disease virus (ADV) DNA in cell cultures and clinical samples. Pigs vaccinated with commercial ADV vaccines and challenged with a field isolate of ADV were immunosuppressed by dexamethasone treatment. Nasal swabs collected from the pigs at various times post-immunosuppression showed that ADV was excreted for at least four to six days starting from day 8 or day 10 following dexamethasone treatment, by virus isolation and/or PCR. However, PCR only detected latent ADV in the trigeminal ganglia, mandibular lymph node, spleen and tonsils, but not in the brain stem, pons and olfactory lobe of two pigs following dexamethasone treatment, whereas tissue explanation and cocultivation failed to demonstrate the presence of the virus. PMID- 8002788 TI - Cowpea aphid borne mosaic virus-Morocco and South African Passiflora virus are strains of the same potyvirus. AB - High performance liquid chromatography (HPLC) profiles of tryptic peptides and partial amino acid sequence analysis have been employed to establish the taxonomic status of the Moroccan isolate of cowpea aphid-borne mosaic virus (CABMV). Some previous reports have suggested CABMV to be very closely related to blackeye cowpea mosaic virus (B1CMV) while other reports have concluded that this relationship is distant. In this report a tryptic digest of the coat protein of CABMV-Morocco was compared with those of the coat proteins of B1CMV-Type, B1CMV W, the mild mottle strain of peanut stripe virus (PStV-MM) and the NY15 strain of bean common mosaic virus (BCMV-NY15), all of which are now recognised as strains of BCMV. The comparisons also included the NL-3 strain of bean necrosis mosaic virus (BNMV-NL3), which had previously been classified as a strain of BCMV. The HPLC peptide profiles indicated that CABMV-Morocco was distinct from BCMV and BNMV. Amino acid sequence analysis of peptides accounting for more than half of the coat protein confirmed that CABMV-Morocco was not a strain of BNMV or BCMV but was a distinct member of the BCMV subset of viruses that previously has been shown to include BCMV, BNMV, soybean mosaic virus, zucchini yellow mosaic virus, passionfruit woodiness virus and South African Passiflora virus (SAPV). Comparison of the partial sequence data with these and other published sequences revealed that the coat protein of CABMV-Morocco is very similar to that of SAPV suggesting that they are strains of the same virus. Since CABMV was described over 25 years earlier than SAPV, the name CABMV should take precedence and SAPV should be renamed CABMV-SAP, the South African Passiflora strain of CABMV. PMID- 8002789 TI - Highly attenuated poxviruses induce functional priming of neutrophils in vitro. AB - Highly attenuated poxvirus samples were used to examine the influence of potential poxvirus expression vector systems on neutrophil function. Exposure to the viruses alters the number of membrane bound complement-and Fc gamma-receptors and led to functional priming of neutrophils to subsequent stimuli. PMID- 8002790 TI - HIV-1 infection of in vitro cultured human monocytes: early events and influence of anti HIV-1 antibodies. AB - To characterize the role of the humoral immune response on HIV-1 infection of monocytes and macrophages (M phi s) we examined the susceptibility of in vitro cultured monocyte/M phi s to various HIV-1 isolates and the influence of heterologous and particularly autologous anti HIV-1 sera on this infection. Depending on the period of in vitro cultivation and the virus isolate used different patterns of susceptibility were detected. One week old monocyte/M phi s were highly susceptible to HIV-1 infection, in contrast to monocyte/M phi s cultured 4 weeks. The infection by virus isolated immediately after seroconversion lead to persistent infection with high level of antigen production in contrast to infection by homologous virus isolated later. MAb against the V3 IIIB loop and sCD4 inhibited the infection of monocyte/M phi s in a dose dependent manner, indicating that infection requires binding to CD4 and that post binding events may be common to the infection of lymphocytes. Anti HIV-1 sera showed neutralizing activity against heterologous and even autologous escape virus. This finding, together with the observation that monocytes and M phi s are infected in vivo, suggests that protection against HIV-1 infection of monocytes and M phi s in vivo may not be obtainable by the humoral immune response alone. PMID- 8002791 TI - Recurrent circulation of single nonstructural gene substitution reassortants among human rotaviruses with a short RNA pattern. AB - To determine the relative frequency of intergenogroup reassortants of rotavirus in nature, we analyzed the genetic composition of 22 electrophoretically distinct stool isolates which accounted for 95.2% of stool rotaviruses with a short RNA pattern collected during 10 rotavirus seasons. These strains all showed subgroup I and G2 specificities, but two distinct hybridization patterns were observed when the probes prepared from Wa (a member of the Wa genogroup) and KUN (a member of the DS-1 genogroup) were used. Genomic RNAs from 10 strains (accounting for 64% of the field rotaviruses with short RNA pattern) hybridized exclusively to the KUN probe, and thus belonged to the DS-1 genogroup. On the other hand, genomic RNAs of the remaining 12 strains (accounting for 36% of the field rotaviruses with short RNA pattern) formed one hybrid band with the Wa probe and 10 hybrid bands with the KUN probe. Thus, they were single gene substitution intergenogroup reassortants between members of the Wa and DS-1 genogroups. They had a similar genetic constellation in that a gene segment encoding either NS35 or NS34 from a Wa-like strain was introduced into a DS-1-like genome background. PMID- 8002794 TI - [6th Spring meeting of the Japanese Society of Allergology. Kumamoto, Japan. April 14-16, 1994. Abstracts]. PMID- 8002792 TI - Radioimmunoprecipitation and immunoblot studies of antibodies to rubella virus in patients with chronic liver disease. AB - Patients with autoimmune chronic active hepatitis (AICAH) and some other chronic liver disorders often have very high titres of rubella HI antibodies. In the present study sera from 46 patients with chronic liver disease and controls were examined for rubella antibodies using radioimmunoprecipitation assay (RIPA) and Western blot. RIPA appeared to be more suitable than Western blot for the study of the individual antibody specificities provided that proteins (possibly actin) interfering with the resolution of the E2 glycoprotein band are identified. It was shown that patients with high rubella HI titres reacted strongly against the E1 glycoprotein and in general also against the core protein (C). Reactivity to the E2 glycoprotein was detected with all sera from patients with chronic liver disease but varied more in strength. Three patients with post-acute rubella showed very faint E2 reactivity, but strong E1 and C reactivities. Patients with primary biliary cirrhosis had normal HI titres and showed no increase in reactivity in RIPA. The present findings show that patients with chronic liver disease and high rubella HI antibody titres exhibit an enhanced specific antibody response to rubella virus structural proteins. PMID- 8002795 TI - [The Mini-Mental State Examination in a general population: impact of educational status]. AB - To assess the influence of age and education on cognitive performance in our population, 530 adults were interviewed using the MMSE (Mini-Mental Status Examination). Education level, classified as illiterate, elementary and middle (< 8 years) and high (> 8 years), was a significant predictor of performance (p < 0.0001). Nevertheless, the total scores were not significantly different among the age-groups, young (< or = 50 years), middle age 51 to 64 years) and elderly (> or = 65 years). The reference cut-off values were taken from the fifth percent lowest score for each group: illiterate, 13; elementary and middle, 18; and high, 26. When compared to 94 patients with cognitive impairment, our cut-off values achieved high sensitivity (82.4% for illiterates; 75.6% for elementary and middle; 80% for high) and specificity (97.5% for illiterate; 96.6% for elementary and middle; 95.6% for high educational level). Education-specific reference values for the MMSE are necessary in interpreting individual test results in populations of low educational level, in order to reduce the false positive results. PMID- 8002796 TI - Fibrodysplasia ossificans progressiva. AB - Fibrodysplasia (myositis) ossificans progressiva (FOP) is a rare autosomal dominant disorder in which there is a progressive ectopic ossification and skeletal malformation, mainly in the connective tissue of muscle. The diagnosis is based on the clinical findings and radiological demonstration of the skeletal malformations. We report a 5 year-old female case with FOP. PMID- 8002793 TI - Rapid detection of African horsesickness virus by the reverse transcriptase polymerase chain reaction (RT-PCR) using the amplimer for segment 3 (VP3 gene). AB - The complete sequence of the major core protein (VP3) gene of African horsesickness virus serotype 4 (AHSV-4; vaccine strain) was determined by analysis of a complete cDNA clone representing segment 3. The RNA was 2,789 bp long and a comparison of its sequence with that of bluetongue virus serotype 10 (BTV-10) revealed 58% nucleotide similarity. Based on these data, the reverse transcriptase-polymerase chain reaction (RT-PCR) technique was applied to the specific detection of AHSV using a pair of primers designed for AHSV-4 VP3 gene. Approximately 230 bp of PCR products were amplified by RT-PCR from the total RNA extracts (mRNA and dsRNA) of Vero cells infected with eight serotypes of AHSV. No product was observed analogous to other orbiviruses. The supernatant of the infected cell culture fluid without any RNA purification was also suitable as a template for RT-PCR after being denatured at 94 degrees C for 5 min. The sensitivity of this method was between 10(0) and 10(1) TCID50 when viral RNA from the supernatant of infected cell culture was subjected to RT-PCR. The whole procedure for detecting the virus RNA by RT-PCR could be carried out within 5 h. The RT-PCR with AHSV VP3 gene as a target was found to be a simple, highly specific and sensitive assay for AHSV. PMID- 8002797 TI - Familial dysautonomia (Riley-Day syndrome). AB - Familial dysautonomia, also known as Riley-Day syndrome, is a disorder of autonomic nervous system with an autosomal recessive mode of inheritance. Reduction and/or loss of unmyelinated and small myelinated fibers is found, as reduction of dopamine beta-hydroxylase in blood. The diagnosis is based on clinical features: diminished lacrimation, insensitivity to pain, poor temperature control, abolished deep tendon reflexes, postural hypotension, vomiting attacks, poor motor coordination, and mental retardation. The treatment is symptomatic and many children die during the first years of life, usually as a result of repeated aspiration pneumonia. We report the case of a 1 year-old child with familial dysautonomia. PMID- 8002798 TI - [Tropical spastic paraparesis in the tropics and Brazil. A historical analysis]. AB - The tropical spastic paraparesis (TSP) is a chronic myelopathy, predominant in the tropics, recently known to be of retroviral origin (HTLV-I). This paper aims at delineating the clinico-etiological evolution of this entity. The historical analysis of it showed that the TSP has had, along decades, many different denominations and the discovery of the retroviral origin for some of them has stimulated new paths of research and epidemiological interest in the tropics and Brazil. PMID- 8002799 TI - Tentative interpretations in psychotherapy. AB - The nature and technique of the tentative interpretation are described. Its usefulness and advantages are outlined, and its field of application in psychotherapy is discussed. PMID- 8002800 TI - [Sexuality. A freudian psychoanalytical concept]. AB - Emphasis is placed in the difficulty in conceptualizing sexuality as a complex and controversial subject. This is a presentation of a concept based on freudian psychoanalysis. With this in mind, many of Freud's references are collected from the Brazilian Standard Edition of the Complete Psychological Works of Sigmund Freud. The following concept is arrived at: sexuality is an instinctive vital energy directed to pleasure, with the possibility of quantitative and qualitative variations, closely bound to homeostasis, to affection, to social relations, to phases of development of childhood-libido, to eroticism, to genitality, to sexual relations, to procreation and to sublimation. PMID- 8002801 TI - [Homage: "The sun rises for all": Jose Ribeiro Portugal--father of Brasilian neurosurgery]. PMID- 8002802 TI - [Evoked potentials by median nerve stimulation: comparison of central conduction time defined by different measure points]. AB - After stimulation of the right median nerve in 20 normal adult volunteers interpeak latency N13-N20 and the difference in onset latency of the components N11-N20 are compared. A fractionation of the last measure was made at the onset of the P13-14 complex. The results concur with the ones in the literature, and it has been observed that all points measured could be obtained without significant difference on the C6-FZ and P3-FZ montages. PMID- 8002803 TI - [Related observations for the use of mounting between neck posterior and scalp in evoked potentials by median nerve stimulation]. AB - Somatosensory evoked potentials after stimulation of the median nerve were obtained in a group of normal individuals. The components obtained between 12 and 22 ms were analysed with cephalic and non-cephalic references. It is shown that the P13-14 complex is the major contributor for the amplitude of the N13 component recorded with electrodes between the posterior neck and the scalp. It has not been possible to detect differences in amplitude or latencies for the components N18 and P22 recorded between FZ-non cephalic and C6-FZ. Implications of these findings to clinical interpretations of the responses are discussed. PMID- 8002804 TI - Central motor conduction in human chronic Chagas' disease. AB - The possible involvement of spinal alpha motor neurons, dorsal root ganglia and sensory fibers in human chronic Chagas' disease was previously demonstrated. More recently neuropsychological and sensory evoked potentials studies suggest the existence of central nervous system abnormalities in these patients. We assessed the state of central motor pathways in 46 patients with chronic Chagas' disease and 30 healthy volunteers by means of percutaneous cortical and spinal electrical stimulation. No significative slowness in pyramidal tracts (PT) conduction was found when comparing both groups. Neither any individual patient exhibited abnormally delayed PT conduction values beyond the upper normal limit of the healthy volunteers. These results suggest that, in contrast with other neural systems, the large myelinated PT fibers are usually spared in human chronic Chagas' disease. PMID- 8002805 TI - [Periodic paralysis: anatomo-pathological study of skeletal muscles in 14 patients]. AB - Periodic paralysis is a rare disease, characterized by transient weakness associated with abnormal levels of serum potassium. Muscle biopsy may show a wide range of abnormalities, vacuoles being more specifically linked to the disease. We analysed 17 muscle biopsies from 14 patients with periodic paralysis (14 hypokalemic, 2 hyperkalemic). All of them showed at least one histological abnormality. Fourteen specimens showed vacuoles that were peripheral, single, frequent and preferentially found in type I fibers. Frequency or severity of attacks did not correlate with the presence of vacuoles but those were more easily found in patients with long term disease. Ten biopsies showed tubular aggregates, specially on the patients with frequent crises or long term disease. A second biopsy was done in three patients and in two we observed a worsening of the histopathologic picture. One patient manifested interictal weakness with evident myopathic changes on the muscle biopsy. Nonspecific changes were found in variable degrees in 15 biopsies. Our study shows that vacuoles and tubular aggregates are frequent changes in periodic paralysis and therefore helpful for the diagnosis. Important myopathic findings in the muscle biopsy suggest a permanent myopathy which probably develops after severe crises or long term disease. PMID- 8002806 TI - [Morphological study of human arachnoid granulations with reference to their classification]. AB - Stereomicroscopic and microscopic study showed human arachnoid granulations with different morphology that we classified in simple and lobate. Simple granulations were small and completely involved by fibrous capsule that delimited a continuous subdural space from the pedicle to the apex. Lobate granulations were bigger than the simple; in the apex the fibrous capsule was thinner than in other regions, and fused with granulation periphery causing interruption of subdural space. Simple granulations might be an initial development stage; lobate granulations would represent a higher development stage, with ideal morphologic structure for absorption of the CSF. PMID- 8002807 TI - [Brain diseases in Campina Grande, Paraiba]. AB - In this study it is shown the incidence of brain diseases in Campina Grande PB, Brazil taking account hospitalizations under prospective payments. Neurologic affections were classified according to ICD-9. It is demonstrated that 3.09% of hospitalizations are due to brain diseases, mainly cerebrovascular disorders. It is evident that Campina Grande is included in Brazil's north-east average of brain diseases representation, and this result contrasts with nation-wide results because of regional differences. Mental disturbances were not included in this study because of the difficulty in obtaining data; they were classified in the other diseases group. PMID- 8002808 TI - [Neuronal ceroid-lipofuscinosis. Report of 4 cases with study by rectal histochemistry, conjunctiva electron microscopy and necropsy]. AB - The authors present the neuropathological and clinical findings of four cases of ceroid lipofuscinosis or Batten's disease. In two cases the autopsy findings showed brain atrophy and nerve cells packed with cytoplasmic granules compatible with lipofuscin. One case was diagnosed by histochemical techniques in frozen sections of rectal biopsy which showed myoenteric ganglion cells with cytoplasmic acid phosphatase positive material as well as numerous macrophages filled with lipofuscin in the mucosae. The fourth case diagnosed by electron microscopy of conjunctival biopsy which showed cytoplasmic inclusions of membranous, curvilinear and fingerprint types. PMID- 8002809 TI - Lipoma of the cerebellopontine angle. Case reports and literature review. AB - Two patients with cerebellopontine angle (CPA) lipoma were studied. They were submitted to surgical treatment. Available literature was reviewed and 29 cases with same lesion were identified which had been treated by surgery. Clinical manifestations, possibility of diagnostic methods, surgical indications and treatment strategies are discussed. Attention is called to the peculiarities of CPA lipomas and the doubtful validity of attempting complete excision in all cases. PMID- 8002810 TI - Increased intracranial pressure in a case of spinal cervical glioblastoma multiforme. Analysis of these two rare conditions. AB - The authors describe a rare case of increased intracranial hypertension consequent to a spinal cervical glioblastoma multiforme in a young patient. They analyse the physiopathology of intracranial hypertension in spinal tumors and the rarity of such kind of tumor in this location, and its clinico-pathological aspects. PMID- 8002811 TI - [Raeder paratrigeminal neuralgia as expression form of intracavernous giant aneurysm]. AB - The authors report the case of a 50-year-old female patient with right orbital headache secondary to a giant intracavernous aneurysm, diagnosed as Raeder paratrigeminal neuralgia. The patient was surgically treated with internal carotid artery trapping together with brain revascularization (superficial temporal artery to a deep branch of the middle cerebral artery). The patient had an excellent outcome. The identity of the syndrome and the differential diagnosis are discussed based on literature review. PMID- 8002813 TI - [Perimesencephalic subarachnoid hemorrhage nonaneurysmatic: report of a case and literature review]. AB - A 42 year-old man with subarachnoid hemorrhage was admitted in our Service (Hunt & Hess grade II). CT-scan disclosed predominantly perimesencephalic subarachnoid hemorrhage. Digital subtraction angiographic study did not disclose either cerebral aneurysm or any other potential site of intracranial bleeding. The evolution was uneventful. A DSA was repeated one month later and was negative. Four months later, the patient was asymptomatic. The authors review the literature and emphasize the importance in recognizing this benign clinical form of nonaneurysmatic subarachnoid hemorrhage. PMID- 8002812 TI - [Internal carotid stump syndrome: report of a case]. AB - The authors describe the case of a patient with transient ischemic attacks (TIAs) from the ipsilateral occluded internal carotid artery (carotid stump syndrome). The patient was submitted to surgical resection of the stump with relief of the symptoms. Thromboembolism from the stump via the anastomotic supply is responsible for the TIAs and is worsened by the blood flow turbulence at this level. PMID- 8002814 TI - [Evoked potentials by median nerve stimulation (SSEP): subcortical components]. PMID- 8002815 TI - [Paracoccidioidomycosis evidencing spinal cord involvement treated with success by fluconazole]. AB - The involvement of central nervous system in paracoccidiodomycosis has rarely been described, with an incidence rate varying from 9.99% to 27.27%. There are two basic forms of clinical presentation: meningeal and tumor-like (abscesses, granulomas, nodules, and cysts). The Paracoccidioides brasiliensis is preferentially described in cerebral hemispheres, cerebellum, medulla oblonga and meninges, and exceptionally in the spinal cord. The authors present a case of paracoccidioidomycosis which diagnosis was achieved by microscopic examination of material from oral lesions and specific serology. The patient presented clinical signs of spinal cord involvement confirmed by lesions found in magnetic resonance imaging. They emphasize the inedit therapeutic response to a new antifungal agent (fluconazole) used for the first time in this kind of clinical manifestation, and the excellent prognosis when diagnosis is promptly made. PMID- 8002816 TI - [Writing tremor: report of a case]. AB - Primary writing tremor is induced by a specific motor activity, generally the handwriting. The case is analyzed under clinic and therapeutic points of view. The patient had a tremor elicited by handwriting without any other concurrent neurologic alteration. He neither presented familiar antecedents nor metabolic, endocrine, iatrogenic, toxic and traumatic ones. As to the therapeutic approach, the tremor did not respond satisfactorily neither to propranolol nor to primidone. But with anticholinergics improvement of the tremor was verified. PMID- 8002817 TI - Cerebellar atrophy related to chronic exposure to toluene. Case report. AB - A 31-year-old woman presented slowly progressing ataxia and neurasthenic symptoms after 14-year occupational exposure to low concentration toluene vapour. Examination disclosed only cerebellar signs. Cognitive functions were normal except moderate visuo-spatial and constructive deficit. CT imaging showed severe pancerebellar atrophy without pathological signs in other brain structures. Two years after she was removed from workplace, CT imaging and ataxia showed no worsening, while visuo-constructive function improved. The authors warn against possible neurotoxic risk associated with this kind of exposure. PMID- 8002818 TI - [Computed tomography in methanol intoxication]. AB - We had the opportunity to follow a methanol intoxication case with CT scans, at the 1st and 6th day after admission. Symmetrical putaminal and white matter lesions were seen on the last CT examination, and occurred with the worsening of neurological manifestations, despite the appropriated treatment. The CT demonstration of brains lesions disclosed the toxic effect of the methanol and could be a guideline to the neurological prognosis. PMID- 8002819 TI - Syndrome of continuous muscle fiber activity. Case report with 11-year follow-up. AB - A 16-year-old male patient who presented with muscle stiffness and dysphonia is described. Electromyography revealed continuous motor activity that was unaffected by peripheral nerve block or general anaesthesia, but was abolished by curare. The patient had a marked improvement after using phenytoin. The follow-up 11-years later corroborates with the proposed benignity of this syndrome, in spite of being dependent on medication. PMID- 8002820 TI - Randomized clinical trials on medical treatment of glaucoma: are they appropriate to guide clinical practice? PMID- 8002821 TI - Randomized clinical trials on medical treatment of glaucoma: are they appropriate to guide clinical practice? PMID- 8002822 TI - Silicone oil vs perfluoropropane gas as a postoperative retinal tamponade. PMID- 8002823 TI - Are antioxidants or supplements protective for age-related macular degeneration? PMID- 8002824 TI - The collaborative Ocular Melanoma Study. PMID- 8002826 TI - Unifocal choroiditis in primary varicella zoster (chickenpox) PMID- 8002825 TI - A potentially serious adverse reaction between sodium fluorescein and promethazine solutions: flush the cannula before injecting. PMID- 8002827 TI - Recovery of useful vision after presumed retinal and choroidal toxic effects from gentamicin administration. PMID- 8002828 TI - Flecked retina associated with cafe au lait spots, microcephaly, epilepsy, short stature, and ring 17 chromosome. PMID- 8002829 TI - Preparing for managed competition. Utilization of ophthalmologic procedures by elderly Medicare beneficiaries. PMID- 8002830 TI - 10 years. Over 10,000 manuscripts. PMID- 8002831 TI - Stargardt's macular dystrophy. PMID- 8002832 TI - Time parameters for glaucoma procedures. AB - Changes in physician reimbursement and the practice environment have emphasized the importance of determining physician time for procedures and services. Forty five percent of the members of the American Glaucoma Society responded to a mail survey of estimates of the length of time and number of visits for the preoperative, operative, and 90-day postoperative care for six common glaucoma procedures. Results suggest a significant underestimation of time for trabeculectomies exists in the original and new resource-based relative value scale work values. Further, 47% to 53% of surgeons hospitalize patients on at least the first postoperative day. There were no apparent time efficiencies between "high-" and "low-volume" respondents. Thus, careful attention should be paid to the accuracy of certain time estimates and the resulting work values in the resource-based relative value scale. Additional work in this and other areas may prove illuminating. PMID- 8002833 TI - A dominant Stargardt's macular dystrophy locus maps to chromosome 13q34. AB - OBJECTIVE: To identify the chromosomal location of a mutated gene that causes an autosomal dominant Stargardt's macular dystrophy. METHODS: Ocular examinations were performed on 67 members of a large kindred to identify those with macular dystrophy. DNA analyses defined the genotype of all family members at 49 polymorphic loci. Linkage between the gene defect responsible for this macular dystrophy and each polymorphic locus was assessed by lodscore calculations. RESULTS: Diminished visual acuity and funduscopic abnormalities were found in 29 family members, which was diagnostic of macular dystrophy. Genetic analyses demonstrated that polymorphic loci from chromosome 13 band q34 were linked to the gene defect in this family. Haplotype analyses localized the disease locus to an 8-centimorgan interval between loci D13S159 and D13S158/D13S174. CONCLUSION: A disease locus responsible for an autosomal dominant Stargardt's macular dystrophy is located on chromosome 13 band q34. Identification of the mutated gene at this locus will lead to a better understanding of macular degeneration. PMID- 8002835 TI - The efficacy of silicone oil for complicated retinal detachments in the pediatric population. AB - OBJECTIVE: To evaluate the efficacy of silicone oil as an intraocular tamponade for complicated retinal detachments in the pediatric population. DESIGN: Case series. SETTING: Referral practice at a major university hospital eye center. PATIENTS: Consecutive referred sample of 48 cases of complicated retinal detachments in children 16 years old or younger. Forty-two percent of the patients had traumatic injuries, and 35 of the eyes had undergone at least one previous retinal surgery. The minimum follow-up was 6 months, with an average follow-up of 23 months. INTERVENTIONS: Pars plana vitrectomy, silicone oil injection, and advanced vitreoretinal surgical techniques. MAIN OUTCOME MEASURES: Successful repair of complicated retinal detachment, improved visual acuity post operatively, and frequency of complications. RESULTS: The postoperative visual acuity at the last follow-up examination was counting fingers or better in eight (17%) of the 48 cases, and only two eyes saw 20/200 or better. In the 46 eyes in which the retinal status could be determined, 16 retinas (35%) were successfully reattached at last follow-up. Significant complications included corneal opacification (62%) and hypotony (58%). Postoperative glaucoma was not a problem. CONCLUSIONS: In the pediatric population with complicated retinal detachments, silicone oil used for intraocular tamponade has disappointing results due to a low rate of sustained retinal reattachment, poor visual rehabilitation, and a high complication rate. PMID- 8002834 TI - Clinical features of a Stargardt-like dominant progressive macular dystrophy with genetic linkage to chromosome 6q. AB - BACKGROUND AND OBJECTIVE: We identified a large family affected with a macular dystrophy whose main clinical features are similar to those of Stargardt's disease. Unlike true Stargardt's disease, the disorder in this family is inherited in an autosomal dominant fashion. We sought to identify the chromosomal location of the disease-causing gene and to clinically define the phenotype in a number of affected family members. METHODS: Thirty-two family members underwent clinical examination. A total of 23 affected family members were identified, and these patients were genotyped at candidate loci with short tandem repeat polymorphisms. The LINKAGE computer program was used for linkage calculations. RESULTS: Affected patients had normal vision in early childhood but began to experience difficulty with central vision between 5 and 23 years of age. Fundus examination early in the disease course revealed flecks in the macula. Central atrophy developed later, with visual acuity decreasing to 20/200 or worse in all patients older than 31 years. Fluorescein angiography revealed no evidence of choroidal silence. Electroretinograms were near normal in younger affected individuals and were most notable for prolonged implicit times in a 73-year-old patient. Chromosome linkage analysis revealed the disease-causing gene to be located near the centromere on the long arm of chromosome 6. The maximum lod score was 5.5 (theta = 0) with marker D6S280. Multipoint analysis resulted in a peak lod score of 6.2 in the interval between markers D6S313 and D6S252 and excluded the interval containing the North Carolina macular dystrophy gene. CONCLUSIONS: This autosomal dominant macular dystrophy is clinically similar to Stargardt's disease, with the exception of its pattern of inheritance. The clearly progressive nature of the disease distinguishes it from North Carolina macular dystrophy, whose causative gene is also located on the long arm of chromosome 6. Identification of the gene involved in this disease may provide clues to the pathogenesis of age-related macular degeneration. PMID- 8002837 TI - Visual function following enucleation or episcleral plaque radiotherapy for posterior uveal melanoma. AB - OBJECTIVE: To evaluate the posttreatment visual performance of patients with a primary posterior uveal melanoma treated by enucleation or plaque radiotherapy. DESIGN: Standardized interview using previously reported interview instrument. SETTING: Referral center. PATIENTS: One hundred two patients with malignant melanoma of choroid or ciliary body, 51 of whom had been treated by primary enucleation and 51 of whom had been treated by plaque radiotherapy. MAIN OUTCOME MEASURES: Vision-related changes in employment status, driving status, reading ability, and television-watching ability during available posttreatment follow up. RESULTS: Forty-eight (94.1%) of the patients who had undergone enucleation and 46 (90.2%) of the patients who had undergone irradiation reported no vision related change in any of four evaluated areas. CONCLUSIONS: The great majority of patients with posterior uveal melanoma retain satisfactory visual performance status for many years after initial treatment, regardless of whether that treatment was enucleation or plaque radiotherapy. PMID- 8002836 TI - The effects of silicone oil removal. Silicone Study Report 6. AB - OBJECTIVE: To evaluate the advisability of removing silicone oil from eyes after surgery for severe (with a classification of at least C-3) proliferative vitreoretinopathy. DESIGN: Subgroup analysis of the Silicone Study, a randomized, multicentered, surgical trial. SETTING: Community- and university-based clinics. PATIENTS: Two hundred twenty-two eyes with severe proliferative vitreoretinopathy followed up in the Silicone Study. INTERVENTIONS: Vitrectomy for proliferative vitreoretinopathy with silicone oil as the intraocular tamponade. OUTCOME MEASURES: Changes in visual acuity, recurrent retinal detachment, and incidence of complications. RESULTS: Ninety-nine (45%) of 222 eyes had surgery for silicone oil removal (oil-removed eyes). Compared with the eyes that did not undergo silicone oil removal (oil-retained eyes) evaluated at a comparable time after oil injection, oil-removed eyes at the examination prior to oil removal were more likely to be attached (85% vs 40%; P < .0001), have a visual acuity of 5/200 or greater (63% vs 35%; P < .0001), and not be hypotonous (5% vs 22%; P < .001). There was no association between the length of oil retention and incidence of recurrent retinal detachment after oil removal. Eyes with attached retinas at the time of oil removal generally improved in visual acuity at the last follow-up examination (P < .0001), which was not evident in eyes with detached retinas at the time of oil removal. In a matched-pair cohort analysis comparing both sets of eyes, there was an increased risk for recurrent retinal detachment at the last follow-up examination in the oil-removed eyes (odds ratio [OR], 2.1; P = .09). However, overall visual acuity improved for oil-removed eyes in 19 (29%) of 66 pairs and for oil-retained eyes in one (2%) of 66 pairs (OR, 19.0; P < .0001). Although nonsignificant, incidence rates of keratopathy (OR, 0.5) and hypotony (OR, 0.5) were lower in oil-removed eyes. CONCLUSION: Removal of silicone oil in anatomically successful eyes significantly increases the likelihood of improved visual acuity with a slight increase in the likelihood of recurrent retinal redetachment. There was a trend for a reduction in the incidence of complications in the oil-removed eyes. PMID- 8002838 TI - Antiphospholipid antibodies in retinal vascular occlusions. A prospective study of 75 patients. AB - OBJECTIVE: To assess the prevalence of antiphospholipid antibodies in patients with occlusive retinal vascular disorders. PATIENTS: Seventy-five consecutive patients (44 with central retinal vein occlusions, 24 with branch venous occlusions, five with vasculitis plus branch venous occlusion, and two with arterial occlusions) were screened for antiphospholipid antibodies and compared with a control group composed of outpatients with similar systemic vascular disorders. RESULTS: The antibody assay for one patient was positive for lupus anticoagulant and the antibody assay for three other patients was positive for anticardiolipin antibodies. These four patients had central or branch retinal vein occlusion and presented with several vascular risk factors. Comparison of the retinal vascular occlusion and the control groups showed no difference in the levels of anticardiolipin antibodies or lupus anticoagulant. CONCLUSIONS: Antiphospholipid antibodies did not seem to be a feature of retinal vein occlusion, but in rare cases (5%) they may contribute to the occlusive phenomenon. A systematic screening does not seem to be justified, but it may be valuable to test for antiphospholipid antibodies in patients without conventional risk factors and in patients with clotting screen abnormalities, particularly if associated with lupus-like syndrome or other elements of the primary antiphospholipid syndrome. PMID- 8002839 TI - Screening for glaucoma in a medical clinic with photographs of the nerve fiber layer. AB - PURPOSE: To evaluate nerve fiber layer photography as a method for glaucoma screening in a general medical clinic setting. METHODS: One hundred seventy-one persons who attended an academic hospital medical clinic were administered a questionnaire and underwent a complete eye examination, including automated perimetry and photography of the optic disc and nerve fiber layer. RESULTS: Eighteen patients were diagnosed as having primary glaucoma; one, secondary glaucoma; and 21 were suspected of having glaucoma. Nerve fiber layer photographs were taken on 145 persons (85%) and were readable in 136 (80%) of the sample of 171 subjects. Nerve fiber layer atrophy was detected on masked evaluation in 64% of those with glaucoma, in 28% of those suspected of having glaucoma, and in 16% of persons who did not meet the criteria for glaucoma. CONCLUSIONS: Nerve fiber layer photography can be carried out as a screening method and can identify a substantial proportion of those with glaucoma. It compares favorably with tonometry, cup-disc ratio estimation, or screening visual field examination for glaucoma detection. PMID- 8002840 TI - Beta-human chorionic gonadotropin, progesterone, and aqueous dynamics during pregnancy. AB - OBJECTIVE: To determine whether the altered hormonal milieu of pregnancy is associated with changes in the dynamics of aqueous humor formation and drainage. DESIGN: Nineteen women were studied during each trimester of a single pregnancy and post partum. Measures of aqueous dynamics included intraocular pressure, aqueous flow, facility of outflow, aqueous flare, and corneal thickness. RESULTS: Pregnancy was associated with relatively lower intraocular pressure, reduced aqueous flare, increased corneal thickness, and increased aqueous outflow facility. Aqueous flow was unchanged. The progesterone level increased during pregnancy and decreased during the postpartum period. The beta-human chorionic gonadotropin level was highest during the first trimester. The progesterone level, but not the beta-human chorionic gonadotropin level, was correlated with intraocular pressure, aqueous flare, and corneal thickness. The change in aqueous outflow facility that accompanied pregnancy could not be correlated directly to changes in beta-human chorionic gonadotropin or progesterone concentrations. CONCLUSIONS: Aqueous flow remains constant during and after pregnancy, but intraocular pressure decreases during pregnancy due to an increase in the outflow facility. The changes in aqueous dynamics are consistent with the hypothesis that excess progesterone during pregnancy blocks the ocular hypertensive effect of endogenous corticosteroids. However, we were unable to find a statistically significant correlation when a direct comparison between the observed changes in outflow facility and the observed changes in the progesterone level was made, perhaps because of intersubject variability of these changes. The changes in intraocular pressure and outflow facility could have been due to one of many other changes in pregnancy that were not measured. PMID- 8002841 TI - Electrophysiologic and electroretinographic evidence for photoreceptor dysfunction as a toxic effect of digoxin. AB - PURPOSE: To investigate photoreceptor dysfunction caused by digoxin toxicity. METHODS: First, a patient who experienced toxic side effects from digoxin was studied acutely by serial electroretinography and later during convalescence. Second, the light responses of isolated photoreceptors exposed to varying amounts of digoxin were studied in vitro. RESULTS: Electroretinographic amplitudes were reduced and implicit times were delayed when digoxin levels were elevated and recovered slowly after return to normal digoxin levels. Isolated photoreceptors exhibited concentration-dependent reductions in the magnitude of the light response during digoxin exposure, suggesting reduction in the dark current due to blockade of the sodium-potassium-adenosine triphosphatase pump. Cones were about 50-fold more sensitive than rods. CONCLUSIONS: Reversible rod and cone dysfunction occur during exposure to toxic levels of digoxin. Photoreceptor dysfunction is probably due to the diminution of the dark current in response to the sodium-potassium-adenosine triphosphatase blockade. PMID- 8002842 TI - The Barbados Eye Study. Prevalence of open angle glaucoma. AB - OBJECTIVE: To describe the design of the Barbados Eye Study and report on the prevalence of open angle glaucoma (OAG) in a predominantly black study population. DESIGN: Population-based prevalence study. SETTING AND PARTICIPANTS: Residents of Barbados, West Indies, identified from a simple random sample of Barbadian-born citizens 40 through 84 years old. DATA COLLECTION: Participants had a comprehensive study visit that included automated perimetry, applanation tonometry, and fundus photography; persons with specific examination findings, as well as a 10% sample of participants, were referred for an ophthalmologic examination and additional tests. OUTCOME: A diagnosis of OAG required both visual field and optic disc criteria for glaucoma damage after excluding other causes. RESULTS: The 4709 participants (83.5% of those eligible) had demographic characteristics that were similar to the census population. Of the 4631 participants who were tested at the study site, 95% completed Humphrey automated perimetry and 97% had photographic or clinical disc gradings; 93% of those referred completed the ophthalmologic examination. In this adult population, the prevalence of OAG by self-reported race was 7.0% (302/4314) in black, 3.3% (6/184) in mixed-race, and 0.8% (1/133) in white or other participants. In black and mixed-race participants, the prevalence reached 12% at age 60 years and older and was higher in men (8.3%) than in women (5.7%), with an age-adjusted male female ratio of 1.4. In addition, over 3% of the participants were classified as having suspect OAG. CONCLUSIONS: To our knowledge, the Barbados Eye Study is the largest glaucoma study ever conducted in a black population and identified more people with OAG than did any previous population study. The prevalence of OAG was high, especially at older ages and in men. Among participants 50 years old or older, one in 11 had OAG, and prevalence increased to one in six at age 70 years or older. The results highlight the public health importance of OAG in the Afro Caribbean region and have implications for other populations. PMID- 8002843 TI - Conditions necessary for the formation of serous detachment. Experimental evidence from the cat. AB - OBJECTIVE: To evaluate experimentally the conditions necessary for the formation of serous detachments. METHODS: Selective injury to the retinal pigment epithelium (RPE) and choriocapillaris was produced in cats using weak laser burns and intense diffuse light, with or without photosensitization with rose bengal. The fundi were analyzed by observation, fluorescein angiography, and histologic examination. RESULTS: Injuring the RPE alone did not cause detachments. Focal injury to the RPE and choriocapillaris caused moderate detachment only when an area surrounding the focal leakage site had been subjected to light damage. Diffuse injury to the RPE and choriocapillaris caused broader detachments. CONCLUSIONS: Three conditions are necessary for serous detachments to form: (1) a source of fluid pressure, (2) a defect in the blood-retinal barrier (entry site), and (3) an area of impaired fluid transport beyond the site of leakage (if fluid is to accumulate over a broader area). PMID- 8002844 TI - Transcorneal oxygenation of the preretinal vitreous. AB - OBJECTIVE: Transcorneal oxygenation is a promising approach to the treatment of various anterior ocular diseases, but its effect on the vitreous and retina is uncertain. The purpose of this study was to evaluate the ocular conditions necessary to permit transcorneal oxygenation of the preretinal vitreous in the rabbit eye. METHODS: Oxygen at atmospheric pressure was supplied via a goggle to the eye while preretinal oxygen tensions were measured with a minimally invasive technique: fluorine-19 (19F) nuclear magnetic resonance spectroscopy of a small preretinal droplet of perfluorotributylamine. Experiments were performed on lensectomized eyes with intact posterior lens capsules (group 1) or in eyes that had also undergone posterior capsular discission (group 2) and mechanical vitrectomy (group 3). To better understand the results of the oxygenation studies, a water-soluble, freely diffusible contrast agent was applied topically to the cornea, and its penetration into the aqueous and vitreous was studied using T1-weighted magnetic resonance imaging. RESULTS: Preretinal PO2 was significantly increased after 30 minutes of transcorneal oxygenation in group 3 eyes (P = .002). In contrast, no change was observed in the other groups despite 30 minutes (group 1) or 3 hours (group 2) of oxygen exposure. The imaging studies demonstrated that contrast penetration of the vitreous was uniform and rapid in eyes in group 3, consistent with a fluid flow-dominated process. A much slower process of anterior and midvitreous enhancement was observed in groups 1 and 2 that was consistent with contrast diffusion. CONCLUSIONS: Because of bulk fluid movement, transcorneal oxygenation of the retina is feasible in single compartment (vitrectomized, lensectomized) eyes within a reasonable period (30 minutes). This finding could prove useful in the treatment of retinal diseases in which hypoxia may play a role. PMID- 8002846 TI - Gazali-Temple syndrome. PMID- 8002845 TI - A clinical study of peripapillary crescents of the optic disc in chronic experimental glaucoma in monkey eyes. AB - OBJECTIVE: We produced chronic experimental glaucoma in 41 monkey eyes and assessed the long-term effects of elevated intraocular pressure on the presence of, and changes in, peripapillary crescents. METHODS: Three readers independently plotted peripapillary crescent size and location using stereo fundus photographs before and after chronic elevation of intraocular pressure in 41 monkey eyes. RESULTS: Crescents were found in a majority of normal eyes. After chronically elevated intraocular pressure, new peripapillary crescents developed in only two eyes. Using planimetric analysis, crescent size was enlarged in five (22%) of the 23 eyes with preexisting crescents. Preexisting crescents became more apparent without change in size in a majority of eyes (reader A, 15 [68%] of 22 eyes; reader B, 17 [74%] of 23 eyes; and reader C, 13 [68%] of 19 eyes). CONCLUSIONS: We conclude that peripapillary crescents are often present in normal monkey eyes but that they do not often undergo dramatic changes in size with chronic intraocular pressure elevation. The presence of a crescent was not significantly associated with the development of optic disc cup enlargement in the experimental monkey eye. PMID- 8002847 TI - A fiberoptic pick-manipulator for vitreoretinal surgery. AB - We have developed a new multifunction instrument for use during bimanual vitreoretinal surgery. The pick-manipulator provides the functions of a vitreoretinal pick, fiberoptic illumination, bipolar diathermy, and irrigation aspiration of fluids and tissues in a single 19- or 20-gauge instrument. PMID- 8002849 TI - Low cholesterol and risk of non-coronary mortality. AB - Based on a systematic review of over 20 cohort studies, a clear association exists, for both men and women, between particularly low cholesterol levels and the rate of non-coronary mortality. The excess in women appears mainly confined to non-cancer causes, particularly respiratory and digestive diseases, while there is also an excess of deaths from cancer seen in men with low cholesterol levels. Higher mortality rates from trauma, haemorrhagic stroke and cirrhosis have also been observed. Much of this association is known to be as a consequence of the disease with a fall in cholesterol levels seen after developing a variety of inflammatory diseases. However, the excess risk of non-coronary heart disease deaths is still apparent by excluding deaths within five years suggesting that effect-cause is not the only explanation. Confounding still remains the most likely explanation for the association with an underlying chronic disease or risk factor causing both the low cholesterol and the fatal event. However, there is still the possibility that some of the increased risk is due to the low cholesterol. This makes it important that appropriately controlled trials of both drug and dietary interventions demonstrate net clinical benefit among those with low levels of coronary risk before cholesterol-lowering strategies are adopted more widely in these groups. PMID- 8002848 TI - Efficacy of drug intervention for lipids in the prevention of coronary artery disease. AB - Meta-analysis of the benefit of drug intervention in hypercholesterolaemia has produced conflicting conclusions, dependent upon which studies were included or which outcomes were considered. We have approached this question by considering coronary artery disease (CAD) outcomes, fatal and non-fatal, in studies considered to be pivotal--those of sufficient size and duration and those achieving sufficient cholesterol reduction to be likely to have a statistically significant outcome. In parallel, we have reviewed all the published angiographic trials of adequate design (randomised and controlled). In four pivotal primary prevention studies, CAD morbidity was reduced in the range 19-45%. CAD mortality was reduced significantly in one of these studies. Women were included in only one study and they did not exhibit the favourable outcome observed in men. In four pivotal secondary prevention studies, CAD morbidity was reduced in the range 5-36%. CAD mortality was significantly reduced in two studies. In eight angiographic intervention studies, lipid intervention was associated with consistently more evidence of regression or stable coronary disease. These studies also yielded suggestive evidence of improved clinical outcome. We conclude that drug intervention to lower cholesterol levels effectively reduces CAD morbidity and mortality in men already suffering from CAD (and may do so in women). Treatment is similarly effective in men with hypercholesterolaemia having no prior history of CAD. We lack evidence of the value of treatment in the elderly or in women having no prior CAD. PMID- 8002850 TI - Cholesterol reduction and death from non-coronary causes: evidence from randomised controlled trials. AB - An overview of randomised trials of cholesterol reduction (26 trials, 50,000 patients, net cholesterol reduction approximately 10%) provides clear evidence of a reduction in the incidence of coronary heart disease (CHD) after just a few years of treatment. Overall, the observed reduction in CHD death (9% +/- 3) was only half as large as the reduction in non-fatal myocardial infarction (19% +/- 4), although both were statistically significant (2p < 0.005). In these trials, 60% of all deaths were from CHD, and since treatment reduced these by about 9%, the expected reduction in total deaths was about 5-6%. This expected reduction falls within the 95% confidence interval of the observed effect of cholesterol reduction on total mortality in these trials. There were small excesses of deaths from cancer and deaths from trauma among patients allocated active treatment. However, in no single trial, nor in the trials collectively, were these increases individually statistically significant. Furthermore, the increases did not appear to be specific to any one agent nor were the increases consistent between trials of the same agent. These observations suggest that the small excesses of non coronary deaths observed in the cholesterol reduction trials may have occurred by chance. Evidence from ongoing longer-term studies of treatments producing larger cholesterol reductions will be useful in further delineating the effects, if any, of such treatments on non-coronary mortality. PMID- 8002851 TI - Declining cardiovascular disease incidence and environmental components. AB - After rising for many years in the mid-to-late 1930s the mortality from ischaemic heart disease (IHD) began to decline in many countries. This represents a decline in both out-of-hospital (community) and hospital deaths. Non-fatal myocardial infarction (MI) has also declined. A literature review was conducted to examine lifestyle and environmental factors contributing to the decline. Half of the decline is attributable to changes in lifestyle and in the known major risk factors. Changes in nutrition appear relevant to the decline, in particular an increased ratio of polyunsaturated to saturated fat intake and a reduced saturated fat intake overall. There is little evidence to support a role of changing alcohol consumption, changing coffee consumption, changing exercise levels or reduction in excess weight in the declining incidence of IHD. While the benefit of smoking cessation is a clear one, its impact on the differing trends in various countries is not clear. Socio-economic factors appear to influence the rate and extent of decline in IHD in different groups and may help explain some of the regional differences in IHD incidence. Reductions in blood pressure within the 'normal range' which may occur with lifestyle changes may also be an important contributor. PMID- 8002852 TI - Percutaneous transluminal coronary angioplasty: clinical and quality of life outcomes one year later. AB - BACKGROUND: The quality of life status of patients prior to and following percutaneous transluminal coronary angioplasty (PTCA) has not been comprehensively investigated. AIM: This study was carried out to determine the effect that PTCA has on patients' quality of life. METHODS: Data on 209 patients were collected one day pre-PTCA and at a mean of two and 11 months post-PTCA. Data on symptomatic status, functional capacity, life satisfaction and psychological well-being were analysed quantitatively. Clinical outcomes, patient perception of PTCA and employment status wee analysed by descriptive statistics. RESULTS: Highly significant improvement in all quality of life measures was found at the early follow-up (p < .001). This improvement was sustained at the late follow-up. At the late follow-up, 58% of patients felt that PTCA had been very beneficial to their health and well-being, and 79% of workers had returned to work. PTCA was primarily successful in 91% of vessels dilated. There were no procedural-related deaths, 12 patients (6%) developed acute occlusion and three patients (1.5%) experienced myocardial infarction (MI). A symptomatic restenosis rate of 16% was found, including 19 patients (9%) requiring repeat PTCA and 14 (7%) undergoing coronary artery bypass grafting (CABG). CONCLUSION: These findings suggest that, after PTCA, the majority of patients experienced improved quality of life which was sustained one year later. PMID- 8002854 TI - HLA non-identical T-cell-depleted bone marrow transplantation for primary immunodeficiency diseases. AB - BACKGROUND: Bone marrow transplantation (BMT) is usually the only procedure offering cure for children with life-threatening immune deficiency disorders, but compatible sibling donors are frequently unavailable. AIMS AND METHODS: To examine the outcome of HLA non-identical T-cell-depleted BMT carried out between April 1985 and May 1992 in 11 patients with primary immunodeficiency diseases and to seek prognostic factors. RESULTS: Eight patients achieved sustained engraftment, one after a second BMT. One further patient engrafted transiently, but rejected the graft five months later. Acute graft-versus-host disease (GVHD) grade II was seen in one and chronic GVHD was seen in three children. Seven patients survived beyond six months, six with donor T cell and five with donor B cell engraftment. At present, five patients (46%) are alive with immune reconstitution at a median follow-up of 14 months (range 6 to 78 months). The major factor associated with outcome was the presence of any infection within one week of BMT (p = 0.01). The presence of lung infection also tended to be a poor prognostic factor (p = 0.06) but did not reach significance, presumably because of the small sample size. HLA non-identical (parental) T-cell depleted BMT plays an important role in the cure of children with immunodeficiencies who do not have an identical sibling donor. Survival can be further improved if the diagnosis of immunodeficiency disease is made early and BMT undertaken before significant infections occur. CONCLUSIONS: The availability of T-cell depleted haploidentical parental bone marrow transplant can be anticipated to improve outcome significantly for children with severe immunodeficiency, especially when diagnosed early. PMID- 8002853 TI - Screening for genetic haemochromatosis in a rheumatology clinic. AB - BACKGROUND: Recent data indicate that the prevalence of genetic haemochromatosis (GH) is greater than previously recognised and suggest that this disease is underdiagnosed. AIMS: To determine the prevalence of GH in rheumatology clinic population. METHODS: Over a 12 month period 339 consecutive patients, mean age 67.0 years, attending a rheumatology clinic were screened for iron overload. RESULTS: Twenty three patients had elevated initial screening tests (transferrin saturation [Tf%] > 55%; ferritin > 500 micrograms/L). Repeat fasting Tf% and ferritin concentrations were obtained in 20 of these patients. Twelve patients had persistently elevated results, and of these patients four had liver biopsy tissue hepatic iron indices consistent with GH. One patient in the group had the diagnosis established by liver biopsy just before the screening commenced. Thus, the prevalence of GH in this population was 1.5%--five times that anticipated for the general population. Three of the patients with GH presented with an arthropathy which was not characteristic of the disease. The increased prevalence of GH in this group of patients with peripheral arthropathy provides an excellent justification for the routine screening of patients with peripheral arthritis for the exclusion of iron overload. PMID- 8002855 TI - Experience with the Gianturco-Roubin stent for abrupt vessel closure complicating percutaneous transluminal coronary angioplasty. AB - BACKGROUND: Emergency coronary artery bypass grafting (CABG) has previously been the only option in the treatment of refractory abrupt vessel closure complicating percutaneous transluminal coronary angioplasty (PTCA), and has been associated with high rates of morbidity and mortality. Intracoronary stenting now provides an alternative to emergency CABG. AIM: To assess our initial experience with emergency coronary artery stenting as a new technique. METHODS: Retrospective case study review with clinical and angiographic follow-up. RESULTS: The Gianturco-Roubin (GR) stent was deployed in 13 patients in whom PTCA was complicated by abrupt vessel closure refractory to standard balloon techniques. Indications for PTCA were unstable angina (six), stable angina (six) and acute myocardial infarction (MI) (one). The arteries stented included left anterior descending (LAD) artery lesions (eight) and right coronary artery lesions (five). Two patients required urgent CABG, one due to failed stent deployment and one for inadequate control of vessel dissection. In seven of the stented patients the creatine kinase rose to greater than twice the upper limit or normal. Three patients had subacute thrombotic occlusion at seven to 19 days post stent deployment, managed with intravenous thrombolysis or repeat PTCA. At seven months follow-up, 11 patients were free of angina, two patients had Canadian Heart Association class II angina and there were no deaths. Eleven patients had repeat angiography at mean six months post stent. Five patients had evidence of restenosis managed with repeat PTCA in four and CABG in one. CONCLUSIONS: The GR stent is an effective alternative to urgent CABG in the treatment of refractory abrupt vessel closure complicating PTCA. PMID- 8002856 TI - The prognosis for end-stage renal failure in spinal cord injury and spina bifida- Australia and New Zealand, 1970-1991. AB - BACKGROUND: The outcome of patients with end-stage renal failure (ESRF) and spinal cord injury or disease has not been clearly documented. AIMS: The aim of this study was to define the prognosis and social consequences for patients with spinal cord injury or spina bifida (SB) treated for ESRF in Australia and New Zealand from 1970 to 1991. METHODS: Fifty patients (two groups: 25--spinal cord injury, 25--SB) were identified retrospectively by questionnaire to individual renal units. Additional information was obtained from the Australia and New Zealand Dialysis and Transplant Registry. Dialysis and transplant history, degree of disability and cumulative survival with integrated treatment were compared between the two groups. RESULTS: Haemodialysis was the most common form of treatment (75.8% of total treatment time in the spinal cord injury group and 66.1% in the SB group). Home or self-care dialysis for a period of more than six months was achieved in 68% of patients in each group. Ten year cumulative survival with integrated treatment was statistically better in the SB group (p < 0.01). In the 42% of all patients who underwent renal transplantation cumulative patient survival was 94% at one year and 82% at five years, with allograft survival being 73% and 70% respectively. In conclusion ESRF and spinal cord injury or SB has a good prognosis in the longer term with an integrated approach to treatment. PMID- 8002857 TI - Oesophageal surfactant: evidence for a possible mucosal barrier on oesophageal epithelium. AB - BACKGROUND: There is a growing body of evidence to indicate that the gastric mucosa is protected against the back-diffusion of acid by a physical barrier comprising surface-active phospholipid (SAPL) otherwise known as gastric surfactant on account of its similarity to pulmonary surfactant in composition and behaviour. AIMS: To determine whether this form of mucosal protection might extend into the oesophagus to offer some degree of protection against the reflux of gastric contents. METHODS: Oesophageal epithelium was tested for the same hydrophobicity which is characteristically imparted to gastric mucosa by SAPL. A morphological study was also performed to visualise any barrier, purposely avoiding conventional fixatives for electron microscopy which destroy hydrophobic surfaces. RESULTS: Oesophageal epithelium in the vicinity of the cardiac sphincter was found to be appreciably hydrophobic, although not as hydrophobic as gastric mucosa. This hydrophobicity was eliminated by bile salts selected as a known 'barrier breaker' and one which reacts with any lining of SAPL. The morphological study revealed much evidence of SAPL, especially that lining epithelial cells, while its source is probably the lamellar bodies also visualised. CONCLUSIONS: These findings indicate a physical barrier of oesophageal surfactant which could offer some degree of protection against gastro oesophageal reflux but one which is particularly prone to attack by bile. PMID- 8002858 TI - The role of high dose 67-gallium scintigraphy in staging untreated patients with lymphoma. AB - BACKGROUND: Gallium-67 (67Ga) scintigraphy has been reported to be of limited value in staging lymphoma patients. However, recent technical advances in radionuclide imaging have potentially enhanced the usefulness of this method. AIMS: The purposes of this study were to determine the current: (1) sensitivity and specificity and (2) impact on clinicians' treatment decisions of 67Ga scans performed at a teaching hospital. METHODS: There were 46 newly presenting patients with lymphoma (13 with Hodgkin's disease (HD) and 33 with non-Hodgkin's lymphoma [NHL]). Planar 67Ga scans were performed up to eight days following injection of 300 MBq (8 mCi) with images interpreted by consensus of two blinded observers; sensitivity and specificity were determined on a lesion by lesion basis in comparison to computed tomography (CT) scans, palpation of peripheral lymph nodes and abdominal lymphangiograms (n = 5). The contribution of 67Ga scans to clinicians' treatment decisions was also independently assessed by an experienced oncologist. RESULTS: Gallium-67 scan sensitivity and specificity were 80% and 96% for HD and 59% and 98% for NHL. Initial treatment plans were modified in three individuals (7%; 95% confidence intervals = 3-10%) due to lesions on the 67Ga scan not prospectively detected or considered equivocal on other tests. CONCLUSIONS: Only a small proportion of newly diagnosed lymphoma patients benefit from staging with state of the art planar high dose 67Ga imaging. PMID- 8002859 TI - Predictors of survival after cerebral infarction: importance of cardiac factors. AB - BACKGROUND: Stroke is the third leading cause of death in much of the developed world. There are two approaches to lowering mortality from stroke: reducing the incidence of stroke and reducing case fatality rate. AIMS: To determine factors, identified at presentation, that were predictive of mortality in elderly persons with acute cerebral infarction. METHODS: A consecutive series of 215 elderly persons admitted to hospital with acute cerebral infarction, confirmed by computerised tomography, were followed for an average of one year. A proportional hazards model was used to identify predictors of mortality. RESULTS: The following variables were identified on univariate analysis as predictors of death: raised serum creatinine, interstitial oedema on chest radiograph, low score on the Mini-Mental State Examination, atrial fibrillation, advanced age, cardiomegaly, raised leucocyte count, pulmonary venous congestion and homonymous hemianopia. Interstitial oedema was the most powerful predictor of death among the four measures of cardiac status. Two successful multivariate models included: 1) interstitial oedema, serum creatinine, age and homonymous hemianopia; 2) serum creatinine and Mini-Mental State Score. Further studies are required to assess the relationship between elevated serum creatinine and poor survival following stroke. PMID- 8002860 TI - Short and long-term results of coronary angioplasty in patients over 75 years. AB - AIMS: This report reviews the outcome of percutaneous transluminal coronary angioplasty (PTCA) on patients aged 75 years or over at this institution, in order to provide statistics that may be useful in managing elderly patients. METHODS: All elderly patients undergoing PTCA between January 1984 and December 1990 were included. Data concerning the PTCA procedure and short term (hospital stay) outcome were compared to those of all patients less than 75 years who underwent PTCA during the same period. Long term outcome was obtained for all surviving elderly patients. RESULTS: One hundred and eleven procedures were performed on patients over 75 years, compared to 3183 procedures on patients under 75. The incidence of PTCA in the elderly increased to 6.7% of all procedures in 1990. Elderly patients were more symptomatic (97% vs 79% in patients under 75 years had Canadian Cardiovascular Society grade 3 or 4 angina), more frequently had the procedure performed urgently (39% vs 14%) and often (67%) had risk factors for PTCA (3 vessel disease, significant left ventricular dysfunction, or a complicating medical illness). Primary success rates (86% vs 90% in patients under 75 years), urgent coronary artery bypass grafting (1.8% vs 1.9%) and Q wave infarction (1.8% vs 1.0%) were similar in the two age groups. In the elderly, procedural difficulties requiring non standard equipment were common (61%), and in-hospital mortality was increased (4.5% vs 0.7%). Additionally, three patients died after discharge resulting in a 30 day mortality of 7.2%. A favourable long term outcome was obtained in 50% of patients at a mean follow up of 20 months. Unfavourable or neutral outcome was due to one or more of the following; death (16%), coronary artery bypass grafting (19%), acute myocardial infarction (7.5%) or significant residual angina (17%). CONCLUSIONS: Highly symptomatic patients over 75 years constitute a high risk group for PTCA, with approximately half obtaining a favourable long term outcome. PMID- 8002862 TI - Profound suppression of plasma alanine aminotransferase activity in children taking vigabatrin. PMID- 8002861 TI - Dyslipidaemia in non-insulin dependent diabetes: the need for a clinical intervention trial. PMID- 8002863 TI - Temporal arteritis in a young patient with a normal erythrocyte sedimentation rate. PMID- 8002864 TI - Cough and glaucoma: a possible association. PMID- 8002865 TI - Thyrotropin in human breast milk. PMID- 8002866 TI - Hepatic failure in fatal exertional heatstroke. PMID- 8002867 TI - Diltiazem-induced acute parkinsonism. PMID- 8002868 TI - Asthma in Australia. PMID- 8002869 TI - Hyaluronic acid and cell adhesion molecules in haematology. PMID- 8002870 TI - Scleroderma and augmentation mammoplasty--a causal relationship? AB - BACKGROUND: The studies implicating a causal relationship between silicone and scleroderma, other autoimmune disease, and fibromyalgia-like symptoms have been largely descriptive with absence of appropriate controls and no consideration of potential confounders. This case control study of augmentation mammoplasty and scleroderma represents an attempt to answer these deficiencies. AIMS: To compare the frequency and temporal relationship of augmentation mammoplasty in interviewed and deceased cases and interviewed controls. To determine the frequencies of exposure to non-augmentation mammoplasty silicone, and to determine the frequencies of mastectomy and breast lumpectomy in interviewed cases and controls. METHODS: Scleroderma cases and age-stratified general practice controls were interviewed using a prepilotted telephone questionnaire. Self-reported date/s of augmentation mammoplasty were ascertained, as were dates of onset of first and second scleroderma symptom/s and scleroderma diagnosis, where relevant. Comparison of socioeconomically adjusted rates was expressed in terms of rate ratios. RESULTS: Augmentation mammoplasty rates were comparable between interviewed cases and controls. No augmentation mammoplasty procedures were documented in deceased scleroderma patients' medical records. Rates of exposure to non-mammoplasty silicone, mastectomy and breast lumpectomy were comparable in interviewed cases and controls. CONCLUSIONS: This study failed to demonstrate an association between silicone breast implantation and the subsequent development of scleroderma, to a relative risk level as low as 4.5 with 90% power. PMID- 8002871 TI - Cholesterol and cardiovascular disease: basic science. AB - Cholesterol is a normal constituent of blood plasma and of cell membranes in every tissue of the body. It is transported in plasma as a component of lipoproteins. Increased concentrations of specific lipoprotein fractions, namely low density lipoproteins (LDL) and intermediate density lipoproteins (IDL), have been implicated both in vitro and in vivo as causes of atherosclerosis. The mechanism by which these lipoproteins initiate atherosclerosis is unknown, although there is growing evidence that it involves interactions between lipoproteins and cells within the artery wall, setting in train complex, reactions which lead ultimately to the fully developed lesions. PMID- 8002872 TI - A review of observational studies on the relationship between cholesterol and coronary heart disease. AB - The likelihood that an association observed in epidemiological studies is one of cause and effect is often evaluated using criteria first put forward by Bradford Hill. The evidence on whether abnormal concentrations of cholesterol and lipoproteins in the blood plasma cause coronary heart disease (CHD) is considered using Bradford Hill's criteria. Evidence from observational studies, backed by evidence from clinical, animal and laboratory studies, leaves no doubt that a high plasma cholesterol concentration is a cause of CHD. PMID- 8002873 TI - Catheter ablation of the atrioventricular node using radiofrequency energy. AB - BACKGROUND: Catheter ablation of the atrioventricular (AV) junction using stored direct current (DC) energy from a standard DC Cardioverter defibrillator was first reported in 1982. Since then many patients have been treated using this procedure for refractory supraventricular arrhythmias, usually atrial fibrillation and flutter. Undesirable thermal effects such as barotrauma and arcing are largely responsible for complications associated with the use of DC energy. This report details our experience of catheter ablation of the AV junction using radiofrequency (RF) energy in a series of 30 consecutive patients. METHODS: RF ablations were performed using steerable Mansfield (Webster Laboratories) 4 mm tipped electrodes and locally assembled RF energy delivery system. RESULTS: The procedure was successful in 27/30 (90%) patients using RF energy, while three patients required DC energy to achieve successful AV junction ablation. General anaesthesia was required in nine patients, six of whom required this for cardioversion to sinus rhythm so that an adequate His Bundle spike could be recorded and three for DC ablation. Dual chamber permanent pacemakers with automatic mode switching were implanted in four patients who had paroxysmal atrial fibrillation or flutter and the remainder had ventricular rate responsive pacemakers. CONCLUSIONS: In patients with drug refractory paroxysmal atrial fibrillation and flutter and in patients with established atrial fibrillation where control of the ventricular rate is difficult, catheter ablation of the AV junction using RF energy is a safe and effective procedure with a high success rate. PMID- 8002874 TI - Cholesterol and non-cardiovascular disease: basic science. AB - Cholesterol metabolism is of fundamental biological importance. This review examines the role of cholesterol metabolism in relation to non-cardiovascular disease (non-CVD). Particular attention is paid to the question of whether or not low levels of cholesterol may have harmful effects on cell function or lead to pathological processes. Many in vitro phenomena have been demonstrated at levels of cholesterol which are very low in comparison to physiological conditions. Nevertheless, low cholesterol is more favourable than high cholesterol for most aspects of cell function. There is no evidence that any catastrophic cellular response or pathological process occurs due to exposure of organisms to low cholesterol. On the other hand, the inflammatory process is a powerful and consistent cause of decreased cholesterol levels. This, together with other confounding factors, appears to explain a major component of the association between low cholesterol levels and non-CVD. PMID- 8002875 TI - Review of dietary intervention studies: effect on coronary events and on total mortality. AB - The perfect randomised controlled dietary prevention trial of coronary heart disease has never been done. The best we can do is to look at all the trials together. Dietary trials should be separated from drug trials because they have different characteristics. Fourteen dietary trials which had disease or death as the end point are collected in this review for a meta-analysis. Three of the trials had two parts (male/female or low fat/increased fish), making a total of 17 trials. All were randomised trials, except the Finnish mental hospital trial which was a 12-year crossover in two hospitals. The trials were primary or secondary, diet only or multifactorial; numbers of subjects range from 52 to 57,460. For total deaths the ratio of intervention/control in all 17 trials is 0.94 (significantly less than 1.00) and for coronary events the pooled odds ratio is 0.87. But in the seven trials with most effective cholesterol lowering the odds ratios are 0.89 for all deaths and 0.70 for coronary events. There is thus no indication of excess all causes mortality in the dietary trials. Four recent secondary prevention trials had angiographic end points. There were a total of 275 subjects; trials were in Holland, USA, Germany and UK. In all trials plasma cholesterol was effectively lowered and coronary narrowing regressed a little, or progressed less in the diet group but significantly compared with controls. These angiographic trials strongly support the results of the major prevention trials. Lastly, a set of ten trials with fish oil after coronary angioplasty are reviewed. In some there appeared to be lower rates of restenosis, but not in all. The mechanism here is different from the major trials with plasma cholesterol lowering diets for longer periods. PMID- 8002877 TI - Characterization of field isolates of Newcastle disease virus using antipeptide antibodies. AB - A recent Australian field isolate of Newcastle disease virus (NDV) was analyzed with antipeptide antibodies capable of differentiating between the sequences at the cleavage activation sites of fusion proteins of different NDV pathotypes. The isolate was found to have the same fusion protein cleavage activation signal as the V4 isolate of the Queensland strain of NDV. However, the isolate failed to react with an antibody specific for the carboxyl-terminal extension on the hemagglutinin/neuraminidase (HN)-protein precursor (HNo-protein) of the V4 isolate and other similar strains (e.g., Ulster and D26). Identity of the fusion protein cleavage activation motif of the isolate was confirmed by chemical analysis of purified fusion protein subunits of the isolate. The combination of a V4-like fusion protein cleavage activation motif but lack of an HNo-protein has not been described before, and the findings indicate that the isolate is a distinct strain of NDV. Analysis of a range of isolates from the state of Victoria, Australia, indicated that similar strains have been present in Australia since at least 1976. Other isolates examined appeared to have fusion protein cleavage activation motifs that could not be defined with the fusion protein-targeted antibodies. These isolates also appeared to lack the HNo-protein characteristic of the Queensland strain. PMID- 8002876 TI - A survey of birds in Denmark for the presence of Pneumocystis carinii. AB - One hundred eighty-three toluidine blue O-stained necropsy lung imprint smears from different avian species were examined microscopically for Pneumocystis carinii. No cyst forms of the organism could be identified. Seventy-eight serum samples from a total of 155 chickens were examined by a competition enzyme-linked immunosorbent assay (ELISA) for antibodies to P. carinii; 53 serum samples were from individual chickens, and 25 samples were pools of sera from two to five chickens. Diluted 1:50, the 78 serum samples showed a specific ELISA-inhibition of 4% to 56% (the 95% confidence limit being 25% to 30% inhibition). Diluted 1:50, nine serum pools representing 34 chickens and 17 of the 53 individual serum samples (32.1%) showed an inhibition greater than 30%. No specific pneumocyst DNA could be detected in serum from 13 of the 53 chickens using polymerase chain reaction and dihydrofolate reductase gene as a specific probe. Specific antibodies to a 116,000-molecular-weight antigen of rat pneumocysts were shown in two (13.3%) of 15 individual chicken serum samples. The results indicate that P. carinii organisms do not commonly reside in the lungs of birds, although some birds may be exposed to external sources of organisms. PMID- 8002878 TI - Effects of aflatoxin B1 on chicken chondrocytes in culture. AB - In vitro effects of aflatoxin B1 on DNA and proteoglycan synthesis were assessed by measuring tritiated thymidine and radiosulfate incorporation by chicken chondrocyte cultures. Chondrocytes were harvested from the growth-plate cartilage of a 35-day-old chicken, cultured in triplicate, and treated with 0, 1, 5, 10, or 25 micrograms aflatoxin B1/ml of culture medium. The cultures were then spiked separately with [3H]thymidine or [35S]sulfate. After the cells, matrix, and medium were harvested, radioactivity was measured by a scintillation counter. Aflatoxin B1 resulted in a dose-dependent inhibition of DNA synthesis, as measured by tritiated thymidine incorporation by chicken chondrocytes: 54.6%, 30.9%, 25.9%, and 5.9% of control in cultures treated with 1, 5, 10, and 25 micrograms aflatoxin B1/ml of culture medium, respectively (P < 0.05). Sulfated proteoglycan synthesis, as measured by radiosulfate incorporation in chondrocyte cultures, was decreased in the media and intercellular matrix by all aflatoxin B1 levels. Compared with controls, 21% less (P < 0.05) radiosulfate was incorporated into non-matrix macromolecules of the medium fraction from chondrocytes exposed to 1 microgram aflatoxin B1/ml. However, 5 micrograms aflatoxin B1/ml was necessary to produce a significant decrease in radiosulfate incorporation in proteoglycans of intercellular matrix (34% less than controls). The ratios of the means of radiosulfate incorporation into intercellular macromolecules to the means of tritiated thymidine incorporation indicated that aflatoxin B1 inhibited DNA synthesis more than proteoglycan synthesis. PMID- 8002879 TI - Amplification of Salmonella chromosomal DNA using the polymerase chain reaction. AB - A Salmonella-specific polymerase chain reaction (PCR) was developed and standardized. The origin of the primers was a recombinant clone (C7) that contained Salmonella-specific HindIII fragment DNA of 2.1-kilobase pairs. Based on the sequence data of Salmonella enteritidis recombinant clone C7, two primers designated NK1 (21 nucleotides) and NK2 (24 nucleotides) were synthesized for use in the PCR. A Salmonella-specific 2.0-kilobase pair DNA product was amplified by the primers from 23 species of Salmonella, but not from 19 enteric and non enteric bacteria. As little as 330 fg of Salmonella DNA was detected using either ethidium bromide/ultraviolet exposure of gels or Southern blot hybridization with a C7 clone. PMID- 8002880 TI - Phenotypic expression of recombinant plasmids pKT107 and pHK11 in an avirulent avian Escherichia coli. AB - An avirulent wild-type avian Escherichia coli strain (Av) was electrotransformed with plasmids coding for complement resistance (pKT107) and Colicin V (ColV) production (pHK11) in order to study the effects of complement resistance and ColV production on virulence. Transformants were also compared with the wild type for embryo lethality, uptake by macrophages, motility, growth rate, plasmid content, and hemolysis. Growth rates and complement resistance patterns of strain Av and transformant Av+pHK11 were similar, but Av+pHK11 caused a significantly greater number of deaths in embryos and acquired motility. Transformant Av+pKT107 had a lower rate of phagocytosis, a slower growth rate, and a greater sensitivity to complement, and it changed from being non-hemolytic to expressing alpha hemolytic action. The 35-kb plasmid present in the wild type was not present in the transformants. Although some of the results demonstrate the difficulties encountered in using wild-type organisms as recipients in virulence studies, the results with Av+pHK11 indicate that ColV production plus the acquisition of motility contributes to the virulence of avian E. coli. PMID- 8002881 TI - Non-association of macrophage phagocytosis and oxidant stimulation with complement resistance and colicin V production by avian Escherichia coli. AB - Avian isolates of Escherichia coli were classified as virulent based on their isolation from chickens with natural cases of colisepticemia, production of colicin V, and complement resistance. A second group of isolates was designated as avirulent based on their isolation from healthy chickens, their inability to produce colicin, and their classification as sensitive or intermediate to the action of complement. In vitro assays of phagocytosis and oxidant production were performed in an attempt to correlate these activities with the ability of each group of bacteria to escape the specific host defense mechanisms of phagocytosis and killing. Although oxidant production regressed with significant linearity on percent phagocytosis, neither group (virulent or avirulent) differed in ability to stimulate peritoneal macrophage phagocytic and oxidant activity when opsonized with normal chicken serum. These results differ from those in mammalian species. PMID- 8002882 TI - Effect of normal intestinal flora of chickens on colonization by virulent colicin V-producing, avirulent, and mutant colicin V-producing avian Escherichia coli. AB - Colonization of the intestinal tracts of newly hatched chicks with Escherichia coli was attempted by swabbing test organisms onto the air-shell of 19-day-old embryos. Test organisms consisted of two virulent E. coli isolates, one avirulent isolate, and one laboratory-derived mutant of the avirulent isolate carrying a recombinant plasmid coding for Colicin V production. Chicks were cultured weekly for 3 weeks for total E. coli and for the test organisms using selective media. Control chicks were sampled on weeks 1 and 5, and the normal E. coli intestinal microflora were examined for the production of colicins. The two virulent E. coli isolates maintained colonization of the chicks for the 3-week test period, with titers decreasing from 10' to 10'- colony-forming units (CFU)/g of intestine. The avirulent isolate and laboratory mutant did not consistently colonize the intestinal tracts. The majority of intestinal samples taken from the control chicks at 1 and 5 weeks had colicin-producing E. coli that were inhibitory to the test organisms. PMID- 8002883 TI - Characterization of an avirulent mutant of a virulent avian Escherichia coli isolate. AB - A virulent, complement-resistant avian Escherichia coli isolate and its avirulent, complement-sensitive, transposon-insertion mutant were compared for the purpose of revealing structures associated with complement resistance. Both had a smooth lipopolysaccharide layer, contained traT, and lacked a capsule, but the mutant possessed a 16.2-kilodalton outer-membrane protein (OMP) not present in the wild-type. This protein may be the product of a coding region interrupted by transposon insertion. Such results suggest that an OMP greater than 16.2 kilodaltons in size may be responsible for the complement resistance and virulence of this wild-type E. coli. PMID- 8002884 TI - Acute renal failure as the cause of death in chickens following intravenous inoculation with avian influenza virus A/chicken/Alabama/7395/75 (H4N8). AB - One-day-old and 5-week-old commercial leghorn, specific-pathogen-free leghorn, and broiler chickens were inoculated intravenously with either avian influenza virus isolate A/chicken/Alabama/7395/75 (H4N8) (Ck/AL) or sterile diluent. Ck/AL infection resulted in a 44% mortality rate, reduced weight gains, and necrosis of proximal renal tubules and/or tubulointerstitial nephritis. The renal tubule necrosis was more severe and widespread in chickens that died than in chickens that were euthanatized. Hyperuricemia, hypercalcemia, and hyperphosphatemia were present in 5-week-old chickens at day 5 postinfection. Influenza virus isolate Ck/AL was nephropathogenic, and death was associated with acute severe renal damage and failure. Some data suggested that the pathogenicity of Ck/AL may be more severe in leghorns than broilers. PMID- 8002885 TI - A survey into the prevalence of poultry helminths in northwest Arkansas commercial broiler chickens. AB - A 12-month survey was conducted to determine the prevalence of poultry helminths in Northwest Arkansas commercial broiler chickens. Intestinal tracts from market ready broilers were collected weekly from two commercial broiler companies; a total of 3542 intestinal tracts were collected for parasite enumeration from 67 company A and 52 company B farms. Ascaridia galli was found on 37.3% of company A farms and 3.9% of company B farms, Raillietina cesticillus was found on 67.2% of company A farms and 69.2% of company B farms, and Heterakis gallinarum was found on 7.5% of company A farms and 1.9% of company B farms. No other parasitic helminths were found. No significant relationship was detected between grow-out feed efficiency and helminth infection rate or magnitude. PMID- 8002887 TI - Evaluation of cell-mediated immunocompetence in mature turkey breeder hens using a dewlap skin test. AB - Cutaneous basophil hypersensitivity (CBH) was evaluated in two experiments using a neck skin (dewlap) test site on adult domestic turkey hens. The CBH response elicited by an intradermal injection of phytohemagglutinin-P (PHA-P) was evaluated by determining dewlap thickness at the injection site immediately before injection and 24, 48, or 72 hr after injection. It was determined that a dose level between 30 and 90 micrograms PHA-P induced a suitable dermal swelling. Laying hens had a dermal response that was about 69% of the response in nonlaying hens. The results indicated that the dewlap test is a rapid, simple, and effective means of assessing a cell-mediated immune response in adult turkey hens. PMID- 8002886 TI - Flow cytometric analysis of B cell and T cell subpopulations in specific-pathogen free chickens infected with infectious bursal disease virus. AB - Lymphocytes obtained from the blood, spleen, and bursa of normal chickens and of chickens infected with infectious bursal disease virus (IBDV) were analyzed for phenotypic expression of CT4, CT8, and immunoglobulin cell surface markers. Single-cell suspensions were stained with monoclonal antibodies by an indirect immunofluorescent assay, and percent staining was quantitated by flow cytometry. Although an appreciable decline from control levels in the percentage of lymphocytes expressing IgM was detected in the spleen and bursa of infected chickens, the relative proportions of lymphocytes expressing CT4 and CT8 in peripheral blood and spleen remained unchanged following infection. These results suggest that whereas humoral immune depression by IBDV may be associated with lysis of antibody-producing B cells, cellular immune depression is not associated with a detectable change in the proportion of helper or cytotoxic/suppressor subpopulations of T lymphocytes. PMID- 8002888 TI - An immunoperoxidase plaque assay for reticuloendotheliosis virus and its application to a sensitive serum neutralization assay. AB - A rapid assay for the enumeration of reticuloendotheliosis virus (REV) is described. Chicken embryo fibroblast monolayer cultures were infected with REV and incubated 6 days under an agar overlay. After removal of the overlay, cells were fixed with acetone/ethanol. Foci of infection (hereafter referred to as plaques) were detected using either an anti-REV envelope monoclonal antibody or convalescent chicken serum as the primary antibody; the secondary antibody was either horseradish peroxidase-conjugated goat anti-mouse IgG (for use with monoclonals) or goat anti-chicken IgG (for use with chicken serum). Staining with a substrate solution containing diaminobenzidine, CoCl2, and H2O2 revealed individual dark plaques on a light gray background. This method worked equally well for the SNV, CSV, and REV-T strains of REV; further, it detected all six field isolates tested. Results indicate that this immunoperoxidase technique is a rapid and reliable method for detection and titration of REV as well as for the assay of neutralizing antibody in chicken serum. PMID- 8002889 TI - Severe pododermatitis in broiler breeder hens housed on pressure-treated slats. AB - Severe foot-pad dermatitis was diagnosed in a case of broiler hens housed on slats made of lumber pressure-treated with chromated copper arsenate. Studies were conducted in an attempt to determine whether contact with the lumber caused the lesions. Breeder pullets were housed for 17 weeks on slats made from either untreated oak or pressure-treated lumber. Cresylic acid disinfectant was applied to one set of each slat type. Foot-pad lesions were scored and tissue arsenic levels were measured. Foot pads of the hens on pressure-treated slats were the only tissue with detectable arsenic levels. All groups developed foot-pad lesions, although the lesions appeared to be most severe, and to have developed earlier, in birds on pressure-treated disinfected slats. PMID- 8002890 TI - Coccidiosis and necrotic enteritis in turkeys. AB - A flock of turkey primary breeder candidates experienced increased mortality within 1 week of being placed in a growout house at 5 weeks 4 days of age. The flock was placed on wood shavings that had been used by an older flock for 2 weeks immediately before placement. Necropsy revealed severe coccidiosis and necrotic enteritis primarily in the distal jejunum, ileum, cecum, and colon. Clostridium perfringens was cultured from intestines. When breeders were selected at 17 weeks of age, total mortality in the affected flock was twice that of a comparable flock placed on fresh litter. Weight at selection in the affected flock was also significantly lower than in flocks placed on fresh litter at the same time in the same growout house. PMID- 8002891 TI - Intestinal diverticulum in a turkey. AB - A normal 21-day-old British United Turkey of America had an intestinal diverticulum. The diverticulum, which affected all layers of the intestinal wall, arose on the mesenteric surface of the ileum midway between the yolk sac and the cecal tonsils. The general structure of the diverticulum resembled the normal histological appearance of the ileum, although a progressive atrophy of the wall occurred throughout the length of the diverticulum. No metaplasia, inflammation, or tumor was observed. PMID- 8002892 TI - An outbreak of infectious laryngotracheitis in California broilers. AB - Infectious laryngotracheitis (ILT) was diagnosed as the cause of an outbreak of respiratory disease in broiler chickens in California. The classical form of ILT is characterized by dyspnea, gasping, coughing, and expectoration of bloody exudate. Most of the broilers submitted to the diagnostic laboratory showed a non classical presentation of ILT, in which mucoid tracheitis and conjunctivitis were the most consistent lesions. Historically, most of the ILT cases diagnosed in our laboratory have consisted of layers with classical signs and lesions. It is not known whether this non classical presentation of ILT in broilers is due to differences in the way broilers respond to ILT infection or to the nature of the ILT virus isolate. PMID- 8002893 TI - Tuberculosis in farmed rheas (Rhea americana). AB - Avian tuberculosis was diagnosed in two mature rheas on different ratite farms over a 2-year period. Both birds had died after progressively losing body condition. Caseonecrotic granulomas were scattered throughout the liver and spleen in both birds. Similar granulomas were in the lung of one bird and bilaterally in the subcutis cranial to the shoulder in the other bird. Smears of several granulomas from both rheas revealed large numbers of acid-fast bacilli. Histologically, the granulomas had caseonecrotic, non-mineralized centers surrounded by giant cells. Large numbers of acid-fast bacilli were seen free in the necrotic material and within inflammatory cells. Amyloidosis of the liver and spleen occurred in one rhea. Mycobacterium avium complex was isolated at a reference laboratory from hepatic granulomas submitted from one rhea. PMID- 8002894 TI - Herpesvirus hepatitis in two eagles in Spain. AB - Two cases of naturally occurring fatal disease in eagles (a booted eagle and a buzzard) are reported. Both eagles showed anorexia, weight loss, weakness, and inability to fly. Microscopically, stained liver sections showed wide non-zonal coagulation necrosis and eosinophilic intranuclear inclusion bodies in hepatocytes adjacent to the edges of necrotic regions. Ultrastructural studies of hepatocytes revealed multiple enveloped viral particles in the cytoplasm, focal paracrystalline arrays of virions within the nuclei, and some budding particles bound by a membrane, located in an evagination of nuclear membrane. The size and morphology of all of these particles were consistent with herpesvirus. To our knowledge, this is the first report of naturally occurring field cases of herpesvirus hepatitis in eagles (Accipitridae). PMID- 8002895 TI - Bilateral duplication of the ceca in a domestic chicken. AB - Bilateral duplication of the ceca in an adult chicken was observed. One characteristic in addition to the duplication was excessive enlargement of one cecum, which contained 336 grams of cecal contents. Undeveloped and developed eggs were also retained in the oviduct because of oviductal atresia. There are few reports of anomalies in domestic fowl (1,2,3,5). Most studies of the incidence of abnormalities in domestic fowl have been assessments of case collections. This paper reports a rare congenital abnormality of the ceca in a domestic chicken, unreported before in the literature, together with atresia of the oviduct and retention of undeveloped and developed eggs in the oviduct. PMID- 8002896 TI - Pathological studies of A/chicken/Alabama/7395/75 (H4N8) influenza virus in specific-pathogen-free laying hens. AB - Specific-pathogen-free laying hens were inoculated with avian influenza virus (AIV) A/chicken/Alabama/7395/75 (H4N8) either intratracheally (IT) or intravenously (IV). IT inoculation produced a localized infection of the upper and lower respiratory tracts with lesions of tracheitis, bronchitis, airsacculitis, and pneumonia around the secondary bronchi. IV inoculation produced a systemic infection with major lesions of nephritis, interstitial pneumonia, salpingitis, and splenic and hepatic necrosis. In IV-inoculated hens, AIV nucleo-protein was demonstrated within renal tubule epithelium, in luminal surface and glandular oviduct epithelium, and in mononuclear cells within pulmonary blood capillaries. However, no virus was recovered from internal contents of eggs laid between days 1.5 and 5 postinfection. These data indicate that A/chicken/Alabama/7395/75 has tissue tropism and pathogenicity for the respiratory and urogenital systems of reproductively active laying hens. Site and severity of lesion development are determined by the localized or systemic nature of AIV infection. PMID- 8002898 TI - Salmonella enteritidis in eggs from commercial chicken layer flocks implicated in human outbreaks. AB - Eggs were cultured from four commercial chicken layer houses implicated in three human outbreaks of Salmonella enteritidis serotype enteritidis infection as part of the activities of the USDA-APHIS, VS, Salmonella enteritidis Task Force. Each house was part of a multiple in-line complex, ranging from three to seven houses. Houses were located on three separate farms, and each house contained between 50,000 and 80,000 chickens. S. enteritidis phage types 8, 13a, and 23 were isolated from samples taken from environmental and organ tissue samples, but only phage type 8 was cultured from eggs. Phage type 8 was isolated from humans in all three S. enteritidis outbreaks. Frequency estimates of contaminated eggs ranged from 0.03% to 0.90%. PMID- 8002897 TI - Effect of genetic selection for increased body weight and sex of poult on antibody response of turkeys to Newcastle disease virus and Pasteurella multocida vaccines. AB - Primary and secondary antibody responses of 671 turkeys of two genetic lines to Newcastle disease virus (NDV) and Pasteurella multocida vaccines were examined. The randombred control line (RBC2) and a subline (F) of RBC2 had been selected for increased 16-week body weight. Poults were vaccinated at 6 and 12 weeks of age, and serum samples were collected 3 weeks after each vaccination. Antibody titers were determined using an enzyme-linked immunosorbent assay. Line F turkeys had significantly higher 9-week and 15-week serum antibody titers to NDV than line RBC2. However, line RBC2 had significantly higher serum antibody titers to P. multocida at 15 weeks of age than line F. The 9-week and 15-week serum antibody titers to NDV were significantly higher in females than males, but males had significantly higher 15-week serum antibody titers to P. multocida than females. Sex of poults did not contribute significantly to variation in serum antibody response to P. multocida at 9 weeks of age. PMID- 8002899 TI - Non-reducible collagen cross-linking in cartilage from broiler chickens with tibial dyschondroplasia. AB - Recent work has shown that hydroxylysylpyridinoline (HP), a non-reducible cross link that stabilizes the collagen fibril network, is significantly greater (over 10-fold) in dyschondroplastic cartilage than in normal growth-plate cartilage in the tibiotarsi of chickens with homocysteine-induced tibial dyschondroplasia (TD). In the present study, broiler chicks with a genetic disposition to TD, as well as normal broiler chicks on a copper-deficient diet alone or supplemented with copper and thiram, were raised for 3 to 4 weeks (Expts. 1 and 2). Their dyschondroplastic cartilage from the proximal tibiotarsus was collected and analyzed for HP as well as lysylpyridinoline (LP) cross-links. Normal growth plate cartilage was obtained from chicks on the copper-deficient diet supplemented with copper. In a third experiment, another set of broiler chicks was raised on a corn/soybean meal-based diet with or without homocysteine, and their articular and sternal cartilage were isolated for cross-link analysis. In the first two experiments, dyschondroplastic cartilage from all birds with induced TD had higher HP and LP concentrations than growth-plate cartilage from birds without TD, although the ratios of HP to LP varied. In the third experiment, the sternal and articular cartilage from birds with homocysteine induced TD appeared normal, having similar HP concentrations in the same types of cartilage in birds without TD. PMID- 8002900 TI - Bordetella avium hemagglutination and motility mutants: isolation, characterization, and pathogenicity. AB - Transposon mutagenesis was used to produce Bordetella avium mutants, which were screened for the lack of potential virulence factors, including a hemagglutinin, flagella, pili, and toxins. A mini-Tn10 transposon containing a kanamycin resistance gene was introduced into the chromosomal DNA of the virulent 002/S isolate by electroporation. A hemagglutination-negative (HA-) mutant and a motility-negative mutant were obtained. Southern blot analysis showed that only the motility-negative mutant contained the transposon, whereas the HA- mutant was a spontaneous kanamycin-resistant mutant. Both mutants were stable in vitro and in vivo. Following inoculation of 2-week-old poults, the HA- mutant was determined to be less virulent than the 002/S parent, whereas the motility negative mutant was similar in virulence to the 002/S parent. These results indicate that the hemagglutinin of B. avium is a virulence factor, but motility does not appear to contribute to virulence. PMID- 8002901 TI - Effect of Eimeria tenella infection on resistance to Salmonella typhimurium colonization in broiler chicks inoculated with anaerobic cecal flora and fed dietary lactose. AB - This study evaluated the effect of Eimeria tenella infection on Salmonella typhimurium colonization of broiler chicks following oral inoculation with anaerobic cecal flora either alone or with a treatment of 10% dietary lactose. The number of chicks colonized by S. typhimurium was significantly lower (P < 0.05) in groups inoculated with cecal flora with or without the dietary lactose treatment than in control groups. In addition, significantly fewer S. typhimurium organisms were isolated from the cecal contents of chicks inoculated with anaerobic cecal flora and treated with 10% dietary lactose than in the control chicks. Infection with E. tenella had no effect on the resistance of treated groups to S. typhimurium colonization of the ceca but did cause higher S. typhimurium colonization in the untreated control chicks. The results indicated that: A) anaerobic cecal flora given orally on the day of hatch to chicks with or without dietary lactose enhanced the resistance of the birds to Salmonella cecal colonization; and B) coccidial infection had no detrimental effect on this resistance to Salmonella colonization. PMID- 8002902 TI - Serotype specificity of B-haplotype influence on the relative efficacy of Marek's disease vaccines. AB - B-haplotype genes in the chicken were previously shown to differentially influence vaccine efficacy against challenge with very virulent Marek's disease virus according to the type of Marek's disease (MD) vaccine used. To determine whether MD vaccines of the same serotype gave comparable levels of protection against MD in chickens of the same haplotype challenged with MD virus strain Md5, two serotype 1 and two serotype 2 vaccines were compared with one serotype 3 vaccine using chickens of 15-B-congenic lines. There was a strong correlation in development of MD lesions among chickens of the different lines receiving the two serotype 2 vaccines (r = 0.94) as well as among chickens receiving the two serotype 1 vaccines (r = 0.76). The serotype 1 vaccines were preferable for B2, B13, B15, and B21, but serotype 2 vaccines were more protective for B5 chickens. The two serotype 2 vaccines gave equivalent protection; however, of the serotype 1 vaccines, CVI988/Rispens provided more protection than Md11/75c/R2/23. We conclude that the B-haplotype influence on MD vaccine efficacy is dependent on the serotype of the vaccine. PMID- 8002903 TI - Invasion of epithelial cell monolayers by turkey strains of Pasteurella multocida. AB - Two serotype 3,4:A strains of Pasteurella multocida that differ in virulence in turkeys were examined for their ability to invade epithelial cell monolayers grown in tissue culture. Both organisms were comparably adherent to cells of turkey kidney origin. However, the virulent strain (86-1913) penetrated primary turkey kidney epithelial cell monolayers at 10 times the level of the low virulence vaccine strain. The virulent strain was also able to invade porcine epithelial cells (PK15) and feline epithelial cells (CRFK) in cell culture. Neither organism invaded rabbit epithelial cells (RK13). Invasion of turkey cells was prevented by inhibition of bacterial protein or RNA synthesis but not by pretreatment of the monolayers with periodate, trypsin, or neuraminidase. Invasion might be a mechanism of pathogenicity for this organism, contributing to colonization or virulence. PMID- 8002904 TI - A retrospective immunohistochemical study of type II avian adenoviral infection in turkey, pheasant, and chicken tissues. AB - A retrospective study of avian cases submitted to the Michigan Animal Health Diagnostic Laboratory between 1986 and 1992 produced four pheasant, five turkey, and five chicken cases in which splenic tissue was positive for type II adenoviral antigen using an agar gel immunodiffusion assay. Tissue sections from these cases were evaluated microscopically using both routine hematoxylin and eosin (H&E) staining and an immunohistochemical staining technique for type II adenoviral antigen. Tissues from all four pheasant cases and four of five turkey cases, but none of the five chicken cases, stained positively by histochemistry. Five additional chicken cases, obtained from the U.S. Department of Agriculture Eastern Laboratory of the Food Safety Inspection Service, had splenic lesions of undetermined etiology; these were also evaluated. One of the five cases had splenic inclusions on H&E staining and had strong positive histochemical staining. The immunohistochemical staining technique was sufficiently sensitive for use on diagnostic tissues that have been routinely fixed in formalin and processed for histopathology, and it detected all three recognized type II adenoviruses. PMID- 8002905 TI - Effect of bacitracin methylene disalicylate on turkey poult performance in the presence and absence of stunting syndrome. AB - This study included a complete factorial arrangement of three dietary levels of bacitracin methylene disalicylate (BMD) (0, 50, and 200 g/ton) and two health conditions (none and stunting syndrome [SS]). One-day-old turkeys were dosed per os with tryptose phosphate broth or a supernatant derived from gastrointestinal tracts of poults with SS. Body weight, feed intake, feed efficiency, water intake, and hydration efficiency were determined at 5, 9, 13, 21, and 27 days of age. BMD at 200 g/ton in the feed significantly improved body weight (P < 0.005) of poults with SS at all ages, and it improved feed efficiency (P < 0.05) from 1 to 9 days of age. BMD at 50 and 200 g/ton improved hydration efficiency (P < 0.05) of poults with SS during the first 9 days of life. PMID- 8002906 TI - Effect of avian influenza virus infection on the phagocytic function of systemic phagocytes and pulmonary macrophages of turkeys. AB - The effects of avian influenza virus (AIV) infection on systemic phagocytes and pulmonary macrophages of turkeys were studied. There was a significant increase (P < 0.0001) in oxidative burst in systemic phagocytes of AIV-inoculated turkeys on 2, 4, 6, and 8 days postinoculation (PI), as measured by chemiluminescence. There was also a significant increase (P < 0.02) in oxidative burst in pulmonary macrophages on day 4 PI. The chemiluminescence response was depressed on 6, 8, and 10 days PI in AIV-inoculated turkeys compared with controls. The increase in oxidative response in both systemic phagocytes and pulmonary macrophages correlated with the peak virus titer in the lungs and trachea of AIV-inoculated inoculated turkeys. Bacterial killing by pulmonary macrophages from AIV inoculated turkeys was reduced on days 6 and 10 PI compared with uninoculated controls. Histopathological changes in trachea were more pronounced on day 6 PI in AIV-inoculated turkeys; no significant changes were detected in the lungs. These data indicate that compromised functional capacity of pulmonary macrophages predisposes turkeys to secondary bacterial infections. PMID- 8002907 TI - Reduced pressure in extended coverage anti-G-trousers with assisted pressure breathing. AB - Six Swedish Air Force pilots and two Armstrong Laboratory subjects volunteered for this study to determine whether reduced pressure in extended coverage anti-G trousers (ECT), in combination with positive pressure breathing for G protection, affected +Gz tolerance. Group mean gradual onset run (GOR) time for the low pressure schedule (0.8 psig.G-1) was significantly different from the other two conditions (1.1, 1.5 psig.G-1)--84.1, 95.6, and 94.1 s, respectively. Group mean simulated aerial combat maneuver (SACM) times statistically differed between the low and middle pressure rates compared to the highest pressure schedule--147.6, 164.8 and 232.3 s, respectively. SACM heart rate (HR) responses for the +9 Gz plateaus were not statistically different among conditions. However, +5 Gz HR's were lower for the highest pressure condition. Similarities were identified between the middle and high pressurization conditions for GOR. However, reducing pressure in the ECT during SACM exposures was not supported by these data. PMID- 8002908 TI - Effect of 28-day head-down bed rest with countermeasures on heart rate variability during LBNP. AB - The effect of exercise and LBNP countermeasures on the cardiovascular deconditioning response have been evaluated by the study of heart rate variability during progressive LBNP tests before, during (day 15), and after 28 d continuous 6 degrees head-down tilt bed rest. Twelve healthy men (age 27-42 years) were studied in two groups. Six were assigned to a countermeasure regime (CM) consisting of strenuous short-term resistance exercise once per day, 6 days per week from day 7 to day 28, combined with lower body negative pressure (LBNP, 28 mm Hg) for 15 min on days 16, 18, 20, and 22-28. Results were compared with data from six subjects, matched on the basis of maximum oxygen uptake, who received no countermeasures (No-CM). The main effects of bed rest were seen in reductions in RR-interval, and in total spectral power. The results of spectral analysis showed a significant reduction in an index of parasympathetic activity with a nonsignificant increase in a sympathetic indicator. The fractal component of heart rate variability was reduced also, suggesting a change in cardiovascular control mechanisms. Although there were significant differences between CM and No CM for a number of variables, there were no bed rest by countermeasure interaction effects in the statistical analysis. These results suggested that this particular series of countermeasures was ineffective in preventing at least certain changes indicative of cardiovascular deconditioning with 28 d head-down tilt bed rest. PMID- 8002909 TI - Effects of different simulated gravity conditions on neuromuscular control in drop jump exercises. AB - The neuromuscular characteristics of the triceps surae muscle were investigated during the various types of stretch-shortening cycle (SSC) muscle loading. The analysis concentrated on the preactivation and the contact phases of SSC. Muscle loading was changed unconventionally by artificially changing the condition of the gravity in drop jumps. This was accomplished by using a special lifting block system where the gravity could be modified to control loading and unloading effects of the triceps surae muscle. The normal gravity condition showed an advantage over the other gravity drop jump conditions for the measured parameters. The same tendency could be seen in the activation characteristics of the investigated muscles in the preactivation and eccentric phases. Further, the preactivation EMG was related to the eccentric peak angular velocity of the ankle joint. The correlation coefficients were 0.37 (p < 0.05) and 0.48 (p < 0.01) for the gastrocnemius and the soleus muscles, respectively. All the results emphasized considerable adaptation of the neuromuscular system to the normal gravity condition. However, the overall control of landing may also depend on the vestibular and visual inputs, which might modify even the earlier learned central programs. PMID- 8002910 TI - Muscular fatigue and recovery following alternating isometric contractions at different levels of force. AB - The purpose of this study was to document the amount and rate of muscular fatigue during alternating levels of isometric contraction similar to that found during the Simulated Aerial Combat Maneuver (SACM). In addition, the time needed to recover from such an exercise was examined. Twenty males between the ages of 22 and 35 years performed an isometric contraction of their right quadriceps muscle at alternating levels of tension (20 and 50% maximum voluntary contraction) until exhaustion. The time at each contraction level was 10 s. After each exhaustive exercise bout, subjects were assigned to one of six recovery intervals (10, 20, 40, 60, 120, and 240 min) followed by a repeat of the exhaustive exercise. All subjects were tested under each of the six recovery intervals. Results showed that the amplitude (RMS) of the myoelectric signal increased while the frequency content of the signal (MPF) decreased over the course of the fatiguing activity. Endurance time (ET) was found to be significantly (p < 0.05) recovered (90.96%) within 60 min after stopping the exercise. Although MPF returned to its prefatigue value within 10 min of rest, the RMS value had still not recovered after 4 h. PMID- 8002911 TI - Burnout and health status in Italian air traffic controllers. AB - This study investigated burnout in air traffic controllers (ATC's). There were 109 Italian ATC's who filled out the Rome Burnout Inventory, a new tool for burnout assessment, during breaks in the working environment. The questionnaire assessed: 1) emotional-mental exhaustion (EME); 2) physical exhaustion (PE); 3) social support by components of the social network; 4) work- and nonwork-related stressors; 5) self-reported psychosomatic and psychiatric disorders. Our data show that the burnout syndrome is closely and positively related to age, years spent in air traffic control, professional dissatisfaction, and to work stressors, but not to nonwork stressors. In our sample, burnout was negatively correlated with social support provided by friends and family. The PE construct seemed to be unreliable in detecting physical burnout in Italian ATC's. Using analysis of variance, subjects with self-reported psychosomatic disorders did not show higher levels of EME scores. Further, EME was positively correlated with self-perceived psychological distress (anxiety, depression and impulse discontrol), but not with physician-rated psychopathology, as revealed by psychoactive drug intake. We suggest that burnout is a construct independent from clinical anxiety or depression. PMID- 8002912 TI - Postural control in pilots and candidates for flight training. AB - Postural control may reflect the pilot's ability to deal successfully with the stresses of spatial orientation. In this study, we hypothesized that fighter pilots would have better performance on the "tetra-axiametric posture test" than would helicopter pilots (less rigorously selected) and candidates for flight training. We tested 28 fighter pilots, 23 helicopter pilots and 43 candidates by tetra-axiametric posturography. Fighter pilots were found on the level position to have significantly more compensatory anterior-posterior sway (moving anterior posterior rather than laterally, p = 0.02) and required less movements to maintain balance (p = 0.02) than did candidates. Helicopter pilots had intermediate values. In stressed positions, fighter pilots demonstrated relatively more slow movements (p = 0.018) than did the candidates, which may be related to increased labyrinth control. In the stressed positions, helicopter pilots had postural profiles similar to the candidates. We conclude that there are significant differences in postural control as tested by tetraaxiametric posturography between fighter pilots, helicopter pilots, and candidates for flight training. This could be due to either innate ability, which could be used in the selection process, or to training. A prospective study is planned in order to determine if posturography can predict a candidate's ability to complete flight training. PMID- 8002913 TI - Switching from forward-looking infrared to night vision goggles: transitory effects on visual resolution. AB - Helmet-mounted displays under development for rotary- and fixed-wing aircraft will allow the user to switch electronically between forward-looking infrared (FLIR) and night vision goggle (NVG) sensors. These sensor transitions potentially involve large changes in display luminance which could transiently impair visual resolution and performance. The purpose of this study was to identify the display luminances which produce a transient reduction in vision when switching from a higher luminance (i.e., FLIR) to a lower luminance (i.e., NVG) display. A letter recognition task was used to assess the effect of luminance adaptation on visual resolution in five subjects. A significant reduction in letter recognition was observed in the first second after switching from simulated FLIR to simulated NVG's when the FLIR luminance was > or = 10 fL. By varying letter size, contrast, and exposure time, the magnitude and duration of visual loss after switching from a bright (49.2 fL) FLIR display were determined. The visual loss lasted up to 4 s, and included a 2x reduction in visual acuity, and a 3x reduction in contrast sensitivity. Large differences in sensor display luminance should be avoided to maintain high levels of visual performance and aviation safety. Design features or training may be necessary to achieve a proper balance between FLIR and NVG luminances which optimize performance and safety without sacrificing the quality of the sensor image. PMID- 8002914 TI - "Bunt bradycardia": two cases of slowing of heart rate inflight during negative Gz. AB - Two cases are presented of Canadian Forces pilots who experienced inflight bradycardia during 15 s of -1 Gz acceleration. The bradycardia was characterized by rapid cardio-deceleration, stable bradycardia, then cardio-acceleration during recovery following the -Gz exposure that was slower than the cardio-deceleration. Vagally mediated bradycardia in humans subjected to -Gz acceleration stress has been previously documented in laboratory studies. This bradycardia may be operationally significant since it signifies the presence of other physiological effects that predispose aviators to reduced subsequent +Gz tolerance. Research to investigate the implications of reduced +Gz tolerance following -Gz acceleration is warranted. PMID- 8002915 TI - Retinal vein occlusions: case reviews of USAF aviators. AB - Retinal vein occlusions are primarily a disease of the elderly, frequently with permanent visual abnormalities. However, both branch and central retinal vein occlusions occur rarely in young individuals. Reported here are a series of retinal vein occlusions in USAF aviators. Seven cases were identified from records of the USAF Armstrong Laboratory Aeromedical Consultation Service from 1976-91. Four cases of central retinal vein occlusions and three cases of branch occlusions are summarized. Initial visual acuity ranged from 20/15 to 20/400. All seven aviators recovered 20/15 vision and returned to flying status. Hyperlipidemia was found in four of the seven aviators, and hypertension was diagnosed in two aviators. Included is a discussion of current concepts in the natural history, associated systemic conditions, treatment options, and aeromedical implications of retinal vein occlusions. PMID- 8002916 TI - Physiologic chest sounds and helicopter engine noise. AB - To develop an amplification system for physiologic chest sounds during air medical transport in jet helicopters, we compared frequency spectra of physiologic chest sounds and Allison C-28 equipped jet helicopter noise. We found that the frequency spectrum of physiologic chest sounds is contained entirely within that of jet rotocraft noise. Attempts to amplify physiologic chest sounds or to filter jet rotorcraft noise will invariably fail to improve perception of chest sounds. Future research must focus on assessment of actual movement of the chest and of each hemithorax, as well as an carbon dioxide production, as indicators of adequate ventilation and proper endotracheal tube position. PMID- 8002917 TI - In flight verification of the inversion illusion. AB - Pilots' sensations of orientation while pushing over (bunting) are inconsistent. We flew 13 aircrew or naive subjects individually in a Hawk or Hunter jet training aircraft. With sun visor down and eyes closed, each was asked to report what the aircraft was doing. After unaccelerated level flight for 30 s, the aircraft was accelerated in level flight from 200 to 250 kts at +0.15 to +0.25 Gx, and gently pulled into a stable 250-kt, 3000 ft/min climb. After 30 s, it was pushed to -1 G during 3 s. Minus 1 G was then held for a further 3 s. Of 30 maneuvers, 14 produced sensations of inversion in 9 of 13 subjects. Two subjects reported feet-up rotation to the inverted; one felt a rotation of indeterminate direction; five felt sudden inversion. This illusion was experienced by 3/3 naive non-pilots, 6/8 pilots, and 0/2 test pilots. We conclude that the "inversion illusion" exists, and that the postulated sensation of backward rotation is often not perceived. PMID- 8002918 TI - Visual evoked potentials through night vision goggles. AB - Night vision goggles (NVG's) have widespread use in military and civilian environments. NVG's amplify ambient illumination making performance possible when there is insufficient illumination for normal vision. While visual performance through NVG's is commonly assessed by measuring threshold functions such as visual acuity, few attempts have been made to assess vision through NVG's at suprathreshold levels of stimulation. Such information would be useful to better understand vision through NVG's across a range of stimulus conditions. In this study visual evoked potentials (VEP's) were used to evaluate vision through NVG's across a range of stimulus contrasts. The amplitude and latency of the VEP varied linearly with log contrast. A comparison of VEP's recorded with and without NVG's was used to estimate contrast attenuation through the device. VEP's offer an objective, electrophysiological tool to assess visual performance through NVG's at both threshold and suprathreshold levels of visual stimulation. PMID- 8002919 TI - Focus adjustment effects on visual acuity and oculomotor balance with aviator night vision displays. AB - Sixteen U.S. Army aviators, who were given training on focus adjustment technique with aviator night vision goggles (NVG), showed an improvement in visual acuity with focus adjustment compared to a fixed infinity focus control. The long-term effect of focus adjustment on vision was not measured; however, adjustment accuracy was found to be generally within acceptable limits based on computer modeling and available physiologic data. Fixed focus eyepieces that are set to a low minus power may partially compensate for instrument myopia, but they may not optimize visual acuity to the extent that adjustable focus eyepieces do. Eyepiece adjustment proficiency with present night vision devices can be improved through training that emphasizes focusing to the least possible minus dioptric power. Future night vision displays can minimize focus misadjustment by providing a tactile zero marking, a limited dioptric adjustment range, and a focusing knob capable of finer adjustment than is available with current NVG's. PMID- 8002921 TI - Animals, alternatives, and humans: solving problems through research in the U.S. Air Force. AB - The Armstrong Laboratory and its predecessors have conducted responsible animal research in support of USAF operations for nearly three decades. The use of animal models, is essential in research that requires a complex living system, but would be too hazardous to humans. The Laboratory also has aggressively pursued alternatives to the use of animals and improved methods in conducting animal research. Thus far, fewer animals are used currently in some areas of research. Since the human is the focus for Armstrong Laboratory research, human test subjects are used as frequently as possible. As improved noninvasive physiologic monitoring methods become available, humans will be used more extensively. PMID- 8002920 TI - A breath sampling device for measuring human exposure to volatile organic compounds in microgravity. AB - A compact device for the collection of alveolar air (breath) from humans aboard spacecraft was developed. The system uses silicone one-way valves that operate independent of gravity, and provide minimal backpressure. Small charcoal filters clean ambient air used for inhalation. The device provided good recoveries of organic compounds at the 20 ng/L level, with generally low carryover of these compounds to a blank sample following a sample at exposure to 100 ng/L. When water accumulated in the system, this carryover increased for highly water soluble compounds. The new device was used in parallel with a larger, previously developed alveolar air sampler that requires gravity for proper operation; comparable results were obtained with the two units. The device measures 47 x 34 x 11.4 cm and weighs approximately 3.2 kg. Sufficient space is available within the case to accommodate a number of sample collection options. PMID- 8002922 TI - Stroke in the young aviator. AB - A robustly healthy aviator experienced a sudden focal impairment in cerebral function from which he rapidly recovered in a manner consistent with the entity known as "spectacular shrinking deficit syndrome." Although brain imaging studies revealed a "lacunar" type lesion involving the caudate nucleus, the clinical picture was much more suggestive of a cardiogenic embolic event. Transthoracic echocardiography was required to demonstrate the probable cause of the stroke (an atrial septal defect). Following surgical repair of the atrial septal defect, the aviator was recommended for waiver to resume duties involving aviation as pilot in command. PMID- 8002923 TI - A comparative evaluation of cognitive-behavioral therapy (CBT) versus exercise therapy (ET) for the treatment of body image disturbance. Preliminary findings. AB - Cognitive-behavioral therapy (CBT) was compared to a combination of aerobic/anaerobic exercise therapy (ET) for the treatment of elevated levels of body image disturbance in college females. CBT consisted of a modification of the 1987 Butters and Cash procedure that was tailored for group intervention; ET consisted of weightlifting and aerobic dancing. Using a counterbalancing procedure, the same therapists conducted both 6-week interventions, which were compared to a nontreated control group. Results revealed equivalent reductions for both treatment groups when compared to controls on measures of body image disturbance reflective of trait and state body weight anxiety, cognitive behavioral aspects of appearance, and overall body dissatisfaction. Unfortunately, few subjects were available for follow-up analyses, preventing an evaluation of the stability of changes. The findings are discussed with regard to the potential role of fitness training as an adjunct to cognitive-behavioral interventions for body image disturbance. PMID- 8002924 TI - Generalizing spontaneous language in developmentally delayed children via a visual cue procedure using caregivers as therapists. AB - Developmentally delayed children are recognized by deficits in language, motor skills, and social interaction. The importance of this topic is demonstrated by the fact that many studies have focused on increasing different aspects of this population's language. New training elements for this population were used here (e.g., the visual cue method was used in home settings). Caregivers were trained as therapists to teach children spontaneous speech by targeting two behaviors. The visual cue method was effective for increasing spontaneous speech in developmentally delayed children in the home. This finding is significant in that home training with caregivers promoted generalization of language by programming common stimuli. Implication of these data for future research is discussed. PMID- 8002925 TI - Validating and teaching affective adult-child interaction skills. AB - A multiple-probe design across three groups of subjects was used to assess adult child interaction skills by graduate students being trained to work with children. These skills were subjected to content and social validation by experts in childhood education and behavior analysis. Subjects in our research evinced generalization across settings. It is therefore suggested that when teaching behavior management, affective skills should also be included in the curriculum. PMID- 8002926 TI - Discrimination training in the treatment of pica and food scavenging. AB - Pica and scavenging are serious, sometimes life-threatening behavior problems among a significant percentage of individuals with mental retardation. This study describes procedures developed to reduce life-threatening pica and food scavenging in two adolescents with severe to profound mental retardation. Treatment was designed to teach the subjects to discriminate safe from unsafe items by training them to ingest only those items put on a specified placemat and to communicate with simple signs or gestures to obtain more food to be put on the mat. Discrimination was achieved by praising subjects when they selected and ingested items from their placemats and delivering a mild punisher when attempts to ingest nonplacemat items were made. A multiple baseline design across settings was used to evaluate the effects of the treatment package in three inpatient settings. All environments were "baited" with both edible and inedible items. Our treatment procedures appeared to be effective in reducing pica in each of the settings. Generalization of treatment effects to natural environments for one of the two subjects was documented. PMID- 8002927 TI - Cognitive-behavioral treatment for adolescent pathological gamblers. AB - This study evaluated the effectiveness of a cognitive-behavioral treatment for adolescent pathological gamblers. Perception of control and severity of the problem served as dependent variables. Four adolescent pathological gamblers meeting DSM-III-R criteria were treated in a multiple baseline design across individuals. Results showed clinically significant changes for all subjects; they remained abstinent at 1-, 4-, and 6-month follow-ups. The clinical implications of these results are discussed. PMID- 8002928 TI - Soluble receptors for cytokines and growth factors: generation and biological function. PMID- 8002930 TI - A novel human airway mucin cDNA encodes a protein with unique tandem-repeat organization. AB - Highly specific affinity-purified polyclonal antibodies against deglycosylated human tracheobronchial mucin was used to select immunoreactive clones from a Uni ZAP cDNA expression library prepared from normal human tracheal mRNA. The largest of three positive clones, designated pAM1, which reacted strongly with the polyclonal antibodies, was further characterized. Sequence analyses revealed a partial 941 bp cDNA that encoded a 313-amino-acid polypeptide. Bases 3-892 consisted of imperfect 41-nucleotide tandem repeats (CCAGGAGGGGACACCGGGTTCACGAGCTGCCCACGCCCTCT) that encoded a unique polypeptide with two types of consensus repeats, TSCPRPLQEGTRV and TSCPRPLQEGTPGSRAAHALSRRGHRVHELPTSSPGGDTGF. The overall composition of the deduced amino acid sequence matched that expected for a mucin protein core and is rich in serine, threonine, proline, glycine and alanine (approximately 51%). Northern blots probed with the mucin cDNA exhibited intense polydisperse hybridization bands with RNA isolated from normal human trachea and cystic-fibrosis bronchus. The data indicate that mucin encoded by clone pAM1 represents a unique type of peptide organization which has not been described in mucin cDNAs reported thus far. PMID- 8002929 TI - Domain assembly of the GLUT1 glucose transporter. AB - A full-length construct of the glucose transporter isoform GLUT1 has been expressed in Sf9 (Spodoptera frugiperida Clone 9) insect cells, and a photolabelling approach has been used to show that the expressed protein binds the bismannose compound 2-N-4-(1-azi-2,2,2-trifluoroethyl)benzoyl-1,3-bis-(D mannos- 4-yloxy)-2-propylamine (ATB-BMPA) and cytochalasin B at its exofacial and endofacial binding sites respectively. Constructs of GLUT1 which produce either the N-terminal (amino acids 1-272) or C-terminal (amino acids 254-492) halves are expressed at levels in the plasma membrane which are similar to that of the full length GLUT1 (approximately 200 pmol/mg of membrane protein), but do not bind either ATB-BMPA or cytochalasin B. When Sf9 cells are doubly infected with virus constructs producing both the C- and N-terminal halves of GLUT1, then the ligand labelling is restored. Only the C-terminal half is labelled, and, therefore, the labelling of this domain is dependent on the presence of the N-terminal half of the protein. These results suggest that the two halves of GLUT1 can assemble to form a stable complex and support the concept of a bilobular structure for the intact glucose transporters in which separate C- and N-domain halves pack together to produce a ligand-binding conformation. PMID- 8002931 TI - Absence of rapid desensitization of the mouse gonadotropin-releasing hormone receptor. AB - Desensitization of gonadotropin release by the pituitary gland in response to gonadotropin-releasing hormone (GnRH) agonists has clinical applications in the treatment of gonadal-hormone-dependent disorders. We therefore investigated possible desensitization of inositol phosphate (IP) responses of GNRH receptors. No short-term homologous desensitization of the IP response to GnRH was observed in either alpha T3 gonadotrope cells line or GH3 cells transfected with GnRH receptor cDNA. The absence of homologous desensitization is unusual among G protein-coupled receptors, and may be due to the absence of a C-terminal cytoplasmic tail, a unique feature of the GnRH receptor. Several potential protein kinase C phosphorylation sites which might mediate heterologous desensitization are present on the GnRH receptor. In both alpha T3 cells and GnRH receptor-transfected Cos-1 cells, activation of protein kinase C by pretreatment with phorbol ester caused a 35-53% decrease in the IP response to GnRH. However, phorbol ester also inhibited guanosine 5'-[gamma-thio]triphosphate-stimulated IP production in permeabilized Cos-1 cells, suggesting that this inhibition is mediated at a post-receptor site. PMID- 8002932 TI - The Ras-related protein R-ras interacts directly with Raf-1 in a GTP-dependent manner. AB - R-ras is a member of the ras family of small GTPases that associates with the apoptosis-suppressing proto-oncogene product Bcl-2. Using the yeast two-hybrid system we provide evidence for an interaction between R-ras and the Raf-1 kinase. This interaction requires only the N-terminal regulatory domain (amino acids 1 256) of Raf-1, and is observed with both the wild type and a constitutively active R-ras mutant, but not with a deletion mutant that lacks the potential effector domain or a mutant of R-ras impaired for GTP binding. Moreover, using an in vitro binding assay we show a direct GTP-dependent interaction of purified R ras with a purified Raf-1 fragment corresponding to the proposed 81-amino-acid H Ras-binding domain of Raf-1 (amino acids 51-131). Taken together, these data indicate that R-ras may exert its biological effect by means of modulating the activity of the Raf-1 kinase as its direct downstream effector. PMID- 8002933 TI - Human glucocerebrosidase catalyses transglucosylation between glucocerebroside and retinol. AB - The basal activity of human placental glucocerebrosidase is elevated 16-fold by n pentanol when assayed using p-nitrophenyl beta-D-glucopyranoside (pNPGlc) as the beta-glucosidase substrate. This enhancement of activity is the result of the formation of a transglucosylation product, n-pentyl beta-D-glucoside, in rate determining competition with the hydrolytic reaction. The transglucosylation product accounts for approximately 80% of the reaction product generated in the presence of n-pentanol (0.18 M) when either glucocerebroside or pNPGlc was used as the substrate. This stimulatory effect can be increased an additional 3-fold by the inclusion of phosphatidylserine (20 micrograms/ml) or sodium taurodeoxycholate (0.3%, w/v) in the incubation medium. In the presence of retinol, glucocerebrosidase also catalyses the synthesis of a novel lipid glucoside, retinyl glucoside, when either glucocerebroside or pNPGlc serves as the substrate. The reaction product was identified as retinyl beta-D-glucoside, based on its susceptibility to hydrolysis by almond beta-D-glucosidase and the subsequent release of equimolar amounts of retinol and glucose. The rate of retinyl-beta-glucoside formation is dependent on the concentration of retinol in the incubation medium, reaching saturation at approximately 0.3 mM retinol. Retinyl beta-D-glucoside is a substrate for two broad-specificity mammalian beta glucosidases, namely the cytosolic and membrane-associated beta-glucosidases of guinea pig liver. However, retinyl beta-D-glucoside is not hydrolysed by placental glucocerebrosidase. These data indicate that the glucocerebrosidase catalysed transfer of glucose from glucocerebroside to natural endogenous lipid alcohols, followed by the action of a broad-specificity beta-glucosidase on the transglucosylation product, could provide mammals with an alternative pathway for the breakdown of glucocerebroside to glucose and ceramide. PMID- 8002934 TI - The expression of functional link protein in a baculovirus system: analysis of mutants lacking the A, B and B' domains. AB - Functional recombinant human link protein has been produced using a baculovirus expression system. In addition to the intact link protein, three mutant forms have also been expressed. Each mutant bears a deletion equivalent to the protein encoded by one exon in the gene. These deletions represent the A domain, which is thought to be responsible for interaction with aggrecan, and the B or B' domains, which are associated with the interaction with hyaluronate. Such deletions split codons spanning exon boundaries, but maintain the reading frame of the protein and result in the correct amino acid being present at the splice junction. All the recombinant proteins appear as two components upon SDS/PAGe, though the abundance of the two forms does vary between preparations, as a result of variable substitution by N-linked oligosaccharides. The recombinant intact link protein was able to interact with both hyaluronate and aggrecan, showing that the baculovirus system is able to produce functional molecules. All of the recombinant mutant link proteins were also able to interact with hyaluronate, indicating that both the B and B' domains can function independently. The recombinant mutant link proteins were also able to interact with aggrecan, with the exception of the mutant lacking the A domain, confirming that this ability resides entirely within this domain. PMID- 8002935 TI - Calcium-induced translocation of annexins to subcellular organelles of human neutrophils. AB - The annexins are Ca(2+)-regulated, phospholipid-binding proteins which have been suggested to take part in cellular events such as exocytosis. The subcellular localization of annexins in human neutrophils was determined using monoclonal antibodies against annexins I, II, IV and VI and a polyclonal peptide antiserum against an annexin consensus sequence. Several annexins were translocated to the light membrane fraction enriched in plasma membranes and secretory vesicles. Annexins were associated also with the azurophil and specific granules. Whereas annexins I, IV and VI and one unidentified 35 kDa protein translocated to each of the isolated organelles, annexin II, a 66 kDa annexin IV-like protein, and a 38 kDa annexin I-like protein exhibited organelle-related differences in their association with membranes. The 38 kDa annexin associated only with specific granules and the secretory vesicles/plasma membrane but not with azurophil granules. Annexin II and the 66 kDa annexin IV-like protein associated with each of the neutrophil organelles, but the binding to specific granules and secretory vesicles/plasma membrane showed a Ca(2+)-dependency different from that of azurophil granules. This observation suggests that these proteins may contribute to the secretory process in neutrophils. PMID- 8002936 TI - Molecular characterization of human stathmin expressed in Escherichia coli: site directed mutagenesis of two phosphorylatable serines (Ser-25 and Ser-63). AB - Stathmin, a probable relay protein possibly integrating multiple intracellular regulatory signals [reviewed in Sobel (1991) Trends Biochem. Sci. 16, 301-305], was expressed in Escherichia coli at levels as high as 20% of total bacterial protein. Characterization of the purified recombinant protein revealed that it had biochemical properties very similar to those of the native protein. It is a good substrate for both cyclic AMP-dependent protein kinase (PKA) and p34cdc2, on the same four sites as the native eukaryotic protein. As shown by m.s., the difference in isoelectric points from the native protein is probably due to the absence of acetylation of the protein produced in bacteria. C.d. studies indicate that stathmin probably contains about 45% of its sequence in an alpha-helical conformation, as also predicted for the sequence between residues 47 and 124 by computer analysis. Replacement of Ser-63 by alanine by in vitro mutagenesis resulted in a ten times less efficient phosphorylation of stathmin by PKA which occurred solely on Ser-16, confirming that Ser-63 is the major target of this kinase. Replacement of Ser-25, the major site phosphorylated by mitogen-activated protein kinase in vitro and in vivo, by the charged amino acid glutamic acid reproduced, in conjunction with the phosphorylation of Ser-16 by PKA, the mobility shift on SDS/polyacrylamide gels induced by the phosphorylation of Ser 25. This result strongly suggests that glutamic acid in position 25 is able to mimic the putative interactions of phosphoserine-25 with phosphoserine-16, as well as the resulting conformational changes that are probably also related to the functional regulation of stathmin. PMID- 8002937 TI - Characterization of insulins and proglucagon-derived peptides from a phylogenetically ancient fish, the paddlefish (Polyodon spathula). AB - The North American paddlefish, Polyodon spathula (Order Acipenseriformes) is an extant representative of a group of primitive Actinopterygian (ray-finned) fish that probably shared a common ancestor with present-day teleosts. Two molecular forms of insulin which differ by a single amino acid substitution, His or Asp at position 15 of the A chain, were isolated from the pancreas of the paddlefish. Paddlefish insulins show greatest structural similarity to insulin from the garfish (order Lepisosteiformes) and resemble mammalian insulins more strongly than do insulins from teleost fish. The primary structures of several proglucagon derived peptides, two molecular forms of glucagon which differ by the single amino acid substitution Arg18-->Ser, and glucagon-like peptide, have been less well conserved during evolution. The paddlefish glucagons contain 31 amino acid residues, rather than the usual 29, and show several structural features, such as Met5, Glu24 and Gly29, not previously observed in glucagons from other species. In spite of considerable differences in structure between paddlefish and mammalian glucagons (10 or 11 amino acid substitutions), both paddlefish glucagons are equally as effective as bovine glucagon in stimulating glycogenolysis in dispersed hepatocytes from the teleost fish Sebastes caurinus (rockfish). However, the substitution Arg18-->Ser in the paddlefish glucagon results in a 6-fold decrease in potency in this system. PMID- 8002938 TI - Fusion between Newcastle disease virus and erythrocyte ghosts using octadecyl Rhodamine B fluorescence assay produces dequenching curves that fit the sum of two exponentials. AB - The kinetics of fusion between Newcastle disease virus and erythrocyte ghosts has been investigated with the octadecyl Rhodamine B chloride assay [Hoekstra, De Boer, Klappe, and Wilschut (1984) Biochemistry 23, 5675-5681], and the data from the dequenching curves were fitted by non-linear regression to currently used kinetic models. We used direct computer-assisted fitting of the dequenching curves to the mathematical equations. Discrimination between models was performed by statistical analysis of different fits. The experimental data fit the exponential model previously published [Nir, Klappe, and Hoekstra (1986) Biochemistry 25, 2155-2161] but we describe for the first time that the best fit was achieved for the sum of two exponential terms: A1[1-exp(-k1t)]+A2[1-exp( k2t)]. The first exponential term represents a fast reaction and the second a slow dequenching reaction. These findings reveal the existence of two independent, but simultaneous, processes during the fusion assay. In order to challenge the model and to understand the meaning of both equation, fusion experiments were carried out under different conditions well known to affect viral fusion (changes in pH, temperature and ghost concentration, and the presence of disulphide-reducing agents or inhibitors of viral neuraminidase activity), and the same computer fitting scheme was followed. The first exponential equation represents the viral protein-dependent fusion process itself, because it is affected by the assay conditions. The second exponential equation accounts for a nonspecific reaction, because it is completely independent of the assay conditions and hence of the viral proteins. An interpretation of this second process is discussed in terms of probe transfer between vesicles. PMID- 8002939 TI - A semi-preparative enzymic synthesis of malonyl-CoA from [14C]acetate and 14CO2: labelling in the 1, 2 or 3 position. AB - A semi-preparative enzymic synthesis of [1-14C]malonyl-CoA from [1-14C]acetate and bicarbonate, and of [3-14C]malonyl-CoA from Na2(14)CO3 and acetate, was achieved by using chloroplasts rapidly isolated from 7-8-day-old pea shoots. Around 70% of the [1-14C]acetate was converted into malonyl-CoA in 2-3 h, and the specific radioactivity of [3-14C]malonyl-CoA synthesized in the system was 25-30 Ci/mol. Reactions were monitored and labelled products were purified by h.p.l.c. PMID- 8002941 TI - Investigation of the nature of the two metal-binding sites in 5-aminolaevulinic acid dehydratase from Escherichia coli. AB - Two distinct metal-binding sites, termed alpha and beta, have been characterized in 5-aminolaevulinic acid dehydratase from Escherichia coli. The alpha-site binds a Zn2+ ion that is essential for catalytic activity. This site can also utilize other metal ions able to function as a Lewis acid in the reaction mechanism, such as Mg2+ or Co2+. The beta-site is exclusively a transition-metal-ion-binding site thought to be involved in protein conformation, although a metal bound at this site only appears to be essential for activity if Mg2+ is to be bound at the alpha-site. The alpha- and beta-sites may be distinguished from one another by their different abilities to bind divalent-metal ions at different pH values. The occupancy of the beta-site with Zn2+ results in a decrease of protein fluorescence at pH 6. Occupancy of the alpha- and beta-sites with Co2+ results in u.v.-visible spectral changes. Spectroscopic studies with Co2+ have tentatively identified three cysteine residues at the beta-site and one at the alpha-site. Reaction with N-ethyl[14C]maleimide preferentially labels cysteine-130 at the alpha-site when Co2+ occupies the beta-site. PMID- 8002940 TI - Cardiac adenylate deaminase: molecular, kinetic and regulatory properties under phosphate-free conditions. AB - Adenylate deaminase (EC 3.5.4.6) may help to regulate the adenine nucleotide catabolism characteristic of such disease states as myocardial ischaemia. We report analysis of the molecular, kinetic and allosteric properties of rabbit heart adenylate deaminase when extracted and purified under phosphate-free conditions (i.e., with Hepes/KOH). The enzyme's subunit molecular mass (approximately 81 kDa), pI (6.5), substrate specificity for 5'-AMP, and activation by K+ were identical in the absence or presence of phosphate. At each chromatographic step during isolation without phosphate, cardiac adenylate deaminase showed a lower apparent activity as compared with the enzyme prepared with phosphate present. Kinetic constants for the phosphate-free rabbit heart adenylate deaminase preparation (Km 0.54 mM AMP; Vmax. 1.4 mumol/min per mg of protein) were approximately 10-fold lower than those of the enzyme isolated with phosphate. The same irreversible decrease in kinetic constants could be achieved by dialysing phosphate from the phosphate-containing enzyme preparation. The relationship between enzyme activity and substrate concentration was sigmoidal in the presence of phosphate, but hyperbolic in its absence. Cardiac adenylate deaminase under phosphate-free conditions was no longer allosterically activated by ATP and ADP, yet remained inhibitable by GTP. Enzyme inhibition by the transition-state mimic coformycin was not influenced by phosphate status. The phosphate-free preparation of rabbit heart adenylate deaminase was markedly labile and extremely susceptible to proteolysis by trypsin or chymotrypsin. The inactivation kinetics and fragmentation pattern in response to controlled proteolysis depended on whether the enzyme had been isolated with or without phosphate present, suggesting a conformational difference between the two enzyme preparations. These data constitute direct evidence that the absence of phosphate irreversibly converts cardiac adenylate deaminase into a pseudo-isoenzyme with distinct kinetic, regulatory and stability properties. PMID- 8002942 TI - Taurolithocholate and taurolithocholate 3-sulphate exert different effects on cytosolic free Ca2+ concentration in rat hepatocytes. AB - Single rat hepatocytes show repetitive oscillations in cytosolic free Ca2+ concentration ([Ca2+]i) when stimulated by agonists acting through the phosphoinositide signalling pathway. We have studied the effect of a natural bile acid, taurolithocholate (TLC), and its sulphated form, taurolithocholate 3 sulphate (TLC-S), on [Ca2+]i in single isolated rat hepatocytes. Although these bile acids are believed to act through a common mechanism to permeabilize the intracellular Ca2+ pool, the [Ca2+]i responses induced by the two compounds were different. Whereas TLC induced a sustained elevation of [Ca2+]i, TLC-S evoked repetitive [Ca2+]i oscillations. In addition, we show that ryanodine, which blocks the Ca(2+)-induced Ca2+ release ('CICR') mechanism, blocked TLC-S-induced oscillations in 50% of hepatocytes, but did not affect the TLC-induced rise in [Ca2+]i. PMID- 8002943 TI - Purification of a novel G-protein alpha 0-subtype from mammalian brain. AB - Three distinct G-protein alpha o-subtypes, i.e. alpha o1, alpha o2 and a newly observed 'alpha o3', are present in membranes of mammalian brain, each appearing as two isoforms on SDS/PAGE. Only alpha o1 and alpha o2 appear to be substrates for pertussis toxin (PTX) when membranes or partially purified proteins are examined. In order to elucidate the apparent PTX-resistance of the third alpha o subtype, we purified alpha o3 from porcine and bovine brain membranes. During the purification procedures, alpha o3 occurred in its dissociated monomeric form and, together with beta gamma-complexes, as a heterotrimer. In a first attempt, we used purified G-protein alpha i/alpha o-mixtures to obtain a final separation of alpha o3. By using f.p.l.c. anion-exchange chromatography on a Mono Q column, complete separation of alpha i1 and alpha o2 was achieved. Partial resolution of alpha o1, alpha i2 and alpha o3 was observed; alpha o3 was eluted between alpha o1 and alpha i2. If alpha o-subunits free from alpha i contaminants were loaded on to the Mono Q column, all three alpha o-subtypes were resolved. The identity of the third subtype as an alpha o-subtype was confirmed by sequence analysis of tryptic fragments. All three alpha o-subtypes bound GTP[S]. Purified alpha o3 was ADP-ribosylated when subjected to PTX treatment in the presence of beta gamma subunits, and on SDS/PAGE the mobility of alpha o3 was similar to that of ADP ribosylated alpha o1. On the basis of results obtained with subtype-specific antibodies, the third alpha o-subtype is immunologically more related to alpha o1 than to alpha o2. Purified alpha o3 failed to reconstitute carbachol-mediated inhibition of Ca2+ current in PTX-pretreated SH-SY5Y-cells, whereas alpha o1 and alpha o2 did successfully restore this effect. We conclude that the novel alpha o3 forms differs from alpha o1 and alpha o2 in its primary structure and may be involved in signal-transduction pathways other than those described for alpha o1 and alpha o2. PMID- 8002944 TI - In vitro biosynthesis of ring-extended cyclosporins. AB - Cyclosporin synthetase, a multifunctional polypeptide, catalyses the biosynthesis of the set of natural cyclosporins. We report that this enzyme is also capable of introducing a beta-alanine into position 7 or 8 of the ring instead of the alpha alanines present at these positions in cyclosporin A. This leads to 34-membered rings in contrast to the 33-membered ring of the cyclo-undecapeptide cyclosporin A. Both [beta Ala7]CyA and [beta Ala8]CyA show immunosuppressive activity. The cyclosporin synthetase-related enzyme peptolide SDZ 214-103 synthetase, on the other hand, does not incorporate either beta-alanine into position 7 or beta hydroxy acids into position 8, confirming the previously described higher substrate specificity of this enzyme compared with cyclosporin synthetase [Lawen and Traber (1993) J. Biol. Chem. 268, 20452-20465]. PMID- 8002945 TI - Decrease in equilibrative uridine transport during monocytic differentiation of HL-60 leukaemia: involvement of protein kinase C. AB - The dose-response curves for the inhibition of equilibrative uridine transport by dilazep, dipyridamole and nitrobenzylthioinosine (NBMPR) in undifferentiated HL 60 cells were biphasic. Some 70% of the transport activity was inhibited with IC50 values of 0.7, 1 and 7 nM respectively. No inhibition of the remaining 30% of transport activity was observed until the dilazep, dipyridamole and NBMPR concentrations exceeded 1, 0.1 and 3 microM respectively. Exposure to phorbol 12 myristate 13-acetate (PMA) for 48 h, to induce monocytic differentiation, caused a 20-fold decrease in Vmax. of both NBMPR-sensitive and NBMPR-insensitive equilibrative uridine transport. The decrease in NBMPR-sensitive uridine transport induced by PMA corresponded to a decrease in NBMPR binding sites. A 30% decrease in specific NBMPR binding sites occurred within 6 h of PMA exposure, and could be prevented by uridine and thymidine at concentrations as low as 100 microM, and by staurosporine at 40 nM. However, the protective effects of these compounds diminished with prolonged PMA exposure. No protection was observed with uracil. Exogenous protein kinase C (PKC) in the presence of ATP and PMA decreased the number of specific NBMPR-binding sites in purified HL-60 cell plasma membranes. These results suggest that a PKC-induced conformational change in substrate-binding/transporting site may be responsible for the decrease in NBMPR sensitive nucleoside transport during PMA-induced monocytic differentiation of HL 60 cells. PMID- 8002946 TI - Recombinant expression of the fdxD gene of Rhodobacter capsulatus and characterization of its product, a [2Fe-2S] ferredoxin. AB - A gene called fdxD that could potentially code for a ferredoxin has recently been identified upstream of the nitrogenase structural genes in Rhodobacter capsulatus [Willison, Pierrard and Hubner (1993) Gene 133, 39-46]. In the present study, the fdxD gene product has been overproduced in Escherichia coli in a soluble form. The recombinant protein, pink in colour, was purified to homogeneity, and biochemically characterized as a new ferredoxin. It represents the fifth ferredoxin so far identified in R. capsulatus and was designated FdV. Its N terminal sequence is identical with that of the native ferredoxin isolated from R. capsulatus. U.v-visible-absorption spectra as well as results of c.d. and e.p.r. spectroscopy demonstrated that the fdxD product contained a [2Fe-2S] cluster correctly assembled and incorporated into the polypeptide. Although similar to plant-type ferredoxins, FdV appeared poorly competent in the photo reduction of NADP+. On the basis of in vitro assays, FdV cannot serve as an electron donor for nitrogenase. The lack of reactivity of FdV in either of these assays may primarily be due to its relatively high mid-point redox potential (E'o = -220 mV, pH 7.5). PMID- 8002947 TI - The inositol 1,4,5-trisphosphate receptor is localized on specialized sub-regions of the endoplasmic reticulum in rat liver. AB - Inositol 1,4,5-trisphosphate (InsP3) is involved in the mobilization of Ca2+ from intracellular non-mitochondrial stores. In rat liver, it has been shown that the InsP3-binding site co-purifies with the plasma membrane. This suggests that in the liver the InsP3 receptor (InsP3R) associates with plasma membrane. We studied the subcellular distribution of the liver InsP3R by measuring the maximal binding capacity of [3H]InsP3 and using antibodies against the 14 C-terminal residues of the type 1 InsP3R. The antibodies recognized a large amount of an InsP3R protein of 260 kDa in a membrane fraction which is also enriched with [3H]InsP3-binding sites and with markers of the basal, the lateral and the bile-canalicular membrane and the plasma-membrane Ca2+ pump (PMCA). The fractions enriched in markers of the endoplasmic reticulum (ER) and the Ca2+ pump of the ER (SERCA2b) contained low levels of InsP3 receptors. The immunofluorescent labelling of cultured hepatocytes with anti-InsP3R antibodies indicated that the receptor is concentrated in the perinuclear area and in some regions near the plasma membrane. The fraction enriched with InsP3R is also contaminated with markers of the ER and with SERCA2b. It was exposed to alkaline medium (pH 10.5) to extract endogenous actin and membrane-associated proteins before being subfractionated by Percoll-gradient centrifugation. The alkaline treatment allowed partial separation of the markers of the ER from the markers of the plasma membrane. The InsP3R was recovered in the heavy subfraction, which was also enriched with markers for the ER and with the SERCA2b and contained low levels of markers of the plasma membrane. These data indicate that the InsP3R is neither localized on the plasma membrane itself nor homogeneously distributed on the ER membrane. This supports the view that part of the receptor is localized on a specialized sub region of the ER which interacts with the plasma membrane. PMID- 8002948 TI - Oxygenation and spontaneous deamination of 2-aminobenzenesulphonic acid in Alcaligenes sp. strain O-1 with subsequent meta ring cleavage and spontaneous desulphonation to 2-hydroxymuconic acid. AB - 2-Aminobenzenesulphonic acid (2AS) is degraded by Alcaligenes sp. strain O-1 via a previously detected but unidentified intermediate. A mutant of strain O-1 was found to excrete this intermediate, which was isolated and identified by m.s., 1H and 13C-n.m.r. as 3-sulphocatechol (3SC). Proteins from cell extracts of strain O-1 were separated by anion-exchange chromatography. A multicomponent oxygenase was observed to convert 1 mol each of NADH, O2 and 2AS into 1 mol each of 3SC, NH3 and NAD+. The enzyme presumably catalysed formation of the ring of a 2-amino 2,3-diol moiety, and elimination in the amino group led to a rearomatization. 3SC was further degraded via meta ring cleavage, which could be prevented by inactivation of the 3-sulphocatechol-2,3-dioxygenase (3SC23O) with 3 chlorocatechol. In Tris buffer, the separated 3SC23O catalysed the reaction of 1 mol each of 3SC and O2 involving a transient yellow intermediate, and release of 1 mol of sulphite and two organic products. The major product was identified by n.m.r. and by g.c./m.s. as 5-carboxypenta-2,4-dien-5-olide (CPDO), an indicator of formation of 2-hydroxymuconic acid (2HM). The second product was identified as the Z,E isomer of 2HM by comparison with authentic material. When the CPDO in the product mixture was chemically hydrolysed to (Z,E)-2HM, 1 mol of (Z,E)-2HM/mol of 3SC was observed. If oxygenation of 3SC by 3SC23O was carried out in phosphate buffer, only a single product was detected, a keto form of 2HM. This dioate was also formed from authentic (Z,E)-2HM in phosphate buffer. Formation of the natural product (Z,E)-2HM from the xenobiotic, 3SC, seems to involve oxygenation to the unstable 2-hydroxy-6-sulphonomuconic acid semialdehyde, which hydrolyses spontaneously to 2HM. There would appear to be at least one spontaneous reaction per enzyme reaction in this pathway. PMID- 8002949 TI - Structure-function studies on human retinol-binding protein using site-directed mutagenesis. AB - Retinol-binding protein (RBP) transports vitamin A in the plasma. It consists of eight anti-parallel beta-strands (A to H) that fold to form an orthogonal barrel. The loops connecting the strands A and B, C and D, and E and F form the entrance to the binding site in the barrel. The retinol molecule is found deep inside this barrel. Apart from its specific interaction with retinol, RBP is involved in two other molecular-recognition properties, that is it binds to transthyretin (TTR), another serum protein, and to a cell-surface receptor. Using site-directed mutagenesis, specific changes were made to the loop regions of human RBP and the resultant mutant proteins were tested for their ability to bind to retinol, to TTR and to the RBP receptor. While all the variants retained their ability to bind retinol, that in which residues 92 to 98 of the loop E-F were deleted completely lost its ability to interact with TTR, but retained some binding activity for the receptor. In contrast, the double mutant in which leucine residues at positions 63 and 64 of the loop C-D were changed to arginine and serine respectively partially retained its TTR-binding ability, but completely lost its affinity for the RBP receptor. Mutation of Leu-35 of loop A-B to valine revealed no apparent effect on any of the binding activities of RBP. However, substitution of leucine for proline at position 35 markedly reduced the affinity of the protein for TTR, but showed no apparent change in its receptor-binding activity. These results demonstrate that RBP interacts with both TTR and the receptor via loops C-D and E-F. The binding sites, however, are overlapping rather than identical. RBP also appears to make an additional contact with TTR via its loop A-B. A further implication of these results is that RBP, when bound to TTR, cannot bind simultaneously to the receptor. This observation is consistent with our previously proposed mechanism for delivery of retinol to target tissues [Sivaprasadarao and Findlay (1988) Biochem. J. 255, 571-579], according to which retinol delivery involves specific binding of RBP to the cell surface receptor, an interaction that triggers release of retinol from RBP to the bound cell rather than internalization of retinol-RBP complex. PMID- 8002950 TI - Ca(2+)-independent arachidonic acid release by vascular endothelium requires protein synthesis de novo. AB - We investigated the mechanism by which the G-protein activators aluminium fluoride and vanadate stimulate arachidonic acid release in pig aortic endothelial cells. Our previous study demonstrated a novel Ca(2+)-independent pathway of phospholipase A2 (PLA2) activation stimulated by aluminium fluoride in this model. In the present study, we found that sodium metavanadate stimulated a rapid concentration-dependent release of [3H]arachidonic acid from prelabelled cells. A more than 3-fold enhancement of arachidonic acid release was achieved in cells treated with 1 mM vanadate for 20 min. Synthesis of prostaglandin products was similarly enhanced. The release of arachidonic acid was not dependent on the presence of extracellular Ca2+, but did require protein synthesis de novo. Both cycloheximide and actinomycin D completely blocked aluminium fluoride- and vanadate-stimulated arachidonic acid release. Because fluoride and vanadate are known protein tyrosine phosphatase inhibitors, it is possible that PLA2 activation occurred secondarily to changes in protein tyrosine phosphorylation. Both aluminium fluoride and vanadate stimulated the rapid phosphorylation of 58, 93 and 120 kDa tyrosine-containing protein substrates. However, in contrast with arachidonic acid release, this response was found to be sensitive to the presence of extracellular Ca2+ and insensitive to blockers of protein synthesis de novo. Furthermore H2O2 treatment resulted in rapid tyrosine phosphorylation of the same substrates without a concomitant increase in arachidonic acid release. These results suggest that the effects of aluminium fluoride and vanadate on PLA2 are not due to changes in protein tyrosine phosphorylation, but do require rapid protein synthesis de novo. PMID- 8002951 TI - Purification of a lysophosphatidic acid-hydrolysing lysophospholipase from rat brain. AB - A lysophosphatidic acid (LPA)-hydrolysing lysophospholipase was purified from rat brain and characterized. This membrane-bound lysophospholipase was solubilized by using n-octyl glucoside and purified by sequential cation, hydrophobic and gel filtration chromatography. The purified protein has a mass of 80 kDa as assayed by SDS/PAGE. This lysophospholipase catalysed the hydrolysis of a variety of lysophosphatidic acids, but with different rates, depending on the length and degree of saturation of the sn-1 acyl group (1-oleoyl-LPA approximately 1 stearoyl-LPA > 1-palmitoyl-LPA > 1-myristoyl-LPA). This enzyme had no-measurable catalytic activity when other lysophospholipids, monoacylglycerol or phosphatidic acid were used as substrates. On the basis of its chromatographic properties, substrate specificity and cellular localization, we conclude that this lysophospholipase differs from those previously purified and speculate that it has an important function in terminating biological responses to LPA. PMID- 8002952 TI - Cold exposure induces different uncoupling-protein thermogenin masking/unmasking processes in brown adipose tissue depending on mitochondrial subtypes. AB - The effect of cold exposure on thermogenic parameters such as mitochondrial protein content, GDP-binding and uncoupling protein (UCP) levels in different mitochondrial fractions from rat brown adipose tissue has been investigated. Rats were exposed from 12 h to 5 days at 4 degrees C, and three mitochondrial fractions were isolated by differential centrifugation: the M1 fraction (1000 g), the M3 fraction (3000 g) and the M15 fraction (15,000 g). Cytochrome c oxidase activity as an index of mitochondrial mass showed an increase during cold exposure. During the first 24 h of cold exposure UCP was incorporated specifically into the M3 and M15 mitochondrial fractions, and thereafter UCP appeared in the heaviest M1 fraction. However, specific GDP binding was increased during the first 24 h in the same way in all subpopulations, and this increase continued up to 72 h of cold exposure. Results suggest that different molecular events are involved during acute and chronic adaptation to cold: during the first 24 h of cold acclimatization, thermogenic activity is increased by an unmasking process of the UCP binding sites in the M1 mitochondrial fraction as UCP levels were constant and GDP binding increased, but in the M3 and M15 fraction the increase in thermogenic activity was completely due to an increase in GDP binding induced by a specific incorporation of UCP targeted to these mitochondria. Thus thermogenic parameters change in a different way in the brown-fat mitochondrial subpopulations during cold acclimatization. PMID- 8002954 TI - Purification and characterization of S-adenosylmethionine-protein-arginine N methyltransferase from rat liver. AB - A protein methylase I (S-adenosylmethionine-protein-arginine N-methyltransferase; EC 2.1.1.23), with a high specificity for recombinant heterogeneous nuclear ribonucleoprotein particle (hnRNP) protein A1, was purified from rat liver. The purification method is simple and rapid; a single initial step of DEAE-cellulose DE-52 chromatography resulted in a 114-fold enrichment from the cytosol, and subsequent Sephadex G-200 chromatography and f.p.l.c. yielded a homogeneous preparation. Ouchterlony double-immunodiffusion analysis indicated that the rat liver enzyme is immunologically different from an analogous enzyme from the calf brain, nuclear protein/histone-specific protein methylase I [Ghosh, Paik and Kim (1988) J. Biol. Chem. 263, 19024-19033; Rajpurohit, Lee, Park, Paik and Kim (1994) J. Biol. Chem. 269, 1075-1082]. The purified enzyme has a molecular mass of 450 kDa on Superose chromatography and 110 kDa on SDS/PAGE, indicating that it is composed of four identical-size subunits. The Km values for protein A1 and S adenosyl-L-methionine were 0.54 x 10(-6) and 6.3 x 10(-6) M respectively. S Adenosyl-L-homocysteine and sinefungin were effective inhibitors of the enzyme with Ki values of 8.4 x 10(-6) M and 0.65 x 10(-6) M respectively. Bivalent metal ions such as Zn2+, Mn2+ and Ni2+ were particularly toxic to the enzyme; at 1 mM Zn2+, 99% of the activity was inhibited. In addition, 50% of the enzyme activity was lost by treatment with 0.12 mM p-chloromercuribenzoate, indicating a requirement for a thiol group for enzyme activity. Glycerol, a compound often used to prevent enzyme inactivation, inhibited over 80% of the activity when present in the reaction mixture at a concentration of 20%. PMID- 8002953 TI - Cytochrome bo from Escherichia coli: reaction of the oxidized enzyme with hydrogen peroxide. AB - Oxidized cytochrome bo reacts rapidly with micromolar concentrations of H2O2 to form a single derivative. The electronic absorption spectrum of this compound differs from that of the oxidized form of the enzyme reported by this laboratory [Watmough, Cheesman, Gennis, Greenwood and Thomson (1993) FEBS Lett. 319, 151 154]. It is characterized by a Soret maximum at 411 nm, increased absorbance at 555 nm, and reduced intensity at 624 nm. The apparent dissociation constant for this process is of the order of 4 x 10(-6) M, and the bimolecular rate constant for the formation of the new compound is (1.25-1.7) x 10(3) M-1.s-1. Electronic absorption difference spectroscopy shows this product to be identical with the compound formed from the reaction of the mixed-valence form of the enzyme with dioxygen. Investigation of this compound by room-temperature magnetic c.d. spectroscopy shows haem o to be neither high-spin nor low-spin ferric, but to have a spectrum characteristic of an oxyferryl species. There is no evidence for oxidation of the porphyrin ring. Therefore the binuclear centre of this species must consist of an oxyferryl haem (S = 1) coupled to a Cu(II) ion (S = 1/2) to form a new paramagnetic centre. The reaction was also followed by X-band e.p.r. spectroscopy, and this showed the disappearance in parallel with the formation of the oxyferryl species, of the broad g = 3.7, signal which arises from the weakly coupled binuclear centre in the oxidized enzyme. Since no new e.p.r.-detectable paramagnetic species were observed, the Cu(II) ion is presumed to be coupled to another paramagnet, possibly an organic radical. There is no evidence in the electronic absorption spectrum to indicate further reaction of cytochrome bo with H2O2 to form a second species. We argue that the circumstances of formation of this oxyferryl species are the same as those for the P form of cytochrome c oxidase, a species often regarded as containing a bound peroxide ion. The implications of these observations for the reaction mechanism of haem-copper terminal oxidases are discussed. PMID- 8002955 TI - Contribution of a buried aspartate residue towards the catalytic efficiency and structural stability of Bacillus stearothermophilus lactate dehydrogenase. AB - The X-ray structure of lactate dehydrogenase (LDH) shows the side-chain carboxylate group of Asp-143 to be buried in the hydrophobic interior of the enzyme, where it makes hydrogen-bonding interactions with both the side-chain hydroxyl group of Ser-273 and the main-chain amide group of His-195. This is an unusual environment for a carboxylate side-chain as hydrogen bonding normally occurs with water molecules at the surface of the protein. A charged hydrogen bonding interaction in the interior of a protein would be expected to be much stronger than a similar interaction on the solvent-exposed exterior. In this respect the side-chain carboxylate group of Asp-143 appears to be important for maintaining tertiary structure by providing a common linkage point between three discontinuous elements of the secondary structure, alpha 1F, beta K and the beta turn joining beta G and beta H. The contribution of the Asp-143 side-chain to the structure and function of Bacillus stearothermophilus LDH was assessed by creating a mutant enzyme containing Asn-143. The decreased thermal stability of both unactivated and fructose-1,6-diphosphate (Fru-1,6-P2)-activated forms of the mutant enzyme support a structural role for Asp-143. Furthermore, the difference in stability of the wild-type and mutant enzymes in guanidinium chloride suggested that the carboxylate group of Asp-143 contributes at least 22 kJ/mol to the conformational stability of the wild-type enzyme. However, there was no alteration in the amount of accessible tryptophan fluorescence in the mutant enzyme, indicating that the mutation caused a structural weakness rather than a gross conformational change. Comparison of the wild-type and mutant enzyme steady state parameters for various 2-keto acid substrates showed the mutation to have a general effect on catalysis, with an average difference in binding energy of 11 kJ/mol for the transition-state complexes. The different effects of pH and Fru 1,6-P2 on the wild-type and mutant enzymes also confirmed a perturbation of the catalytic centre in the mutant enzyme. As the side-chain of Asp-143 is not sufficiently close to the active site to be directly involved in catalysis or substrate binding it is proposed that the effects on catalysis shown by the mutant enzyme are induced either by a structural change or by charge imbalance at the active site.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8002956 TI - Polyunsaturated-fatty-acid oxidation in Hydra: regioselectivity, substrate dependent enantioselectivity and possible biological role. AB - A novel and abundant lipoxygenase-like activity converting cis-eicosa-5,8,11,14 tetraenoic acid (arachidonic acid) into (11R)-hydroxyeicosatetraenoic acid has been recently described in homogenates of the freshwater hydrozoan Hydra vulgaris. In this study, other substrates for this enzyme were selected from the polyunsaturated fatty acids (PUFAs) present in H. vulgaris, and the chemical natures of the hydroperoxy and hydroxy derivatives produced, as well as the activity of some of the latter on hydroid tentacle regeneration, were investigated. The highest conversion among C20 fatty acids was observed for arachidonic acid, and among C18 fatty acids for cis-octadeca-9,12,15- and cis octadeca-6,9,12-trienoic (alpha- and gamma-linolenic) acids. Cis double bonds on the 10th carbon atom from the aliphatic end of the substrate (e.g. C-9, C-11 and C-13 respectively in C18, C20 and C22 PUFAs) were regiospecifically peroxidized. Conversely, trans-octadeca-9,12-dienoic (linoelaidic) acid was not a substrate for lipoxygenase activity. Enantioselectivity of lipoxygenation depended on the degree of unsaturation of the substrate, with the amount of the R enantiomer increasing when passing, for example, from cis-eicosa-11,14-dienoic to cis-eicosa 5,8,11,14,17-pentaenoic acid. Regiospecific formation of keto acids was observed only when incubating C18 PUFAs. Commercially available hydroxyacids corresponding to the reaction products of some of the most abundant H. vulgaris PUFAs were tested for effects on Hydra tentacle regeneration. An enhancement of average tentacle number, in a fashion depending on the stereochemistry and on the number of double bonds, was found for two compounds, thus suggesting for the 11 lipoxygenase-like enzyme a role in the production of metabolites potentially active in the control of hydroid regenerative processes. PMID- 8002958 TI - Surface-area cycling of different surfactant preparations: SP-A and SP-B are essential for large-aggregate integrity. AB - Surface-area cycling is an in vitro procedure for the conversion of large into small surfactant aggregates. In this procedure a tube containing a surfactant suspension is rotated end-over-end at 37 degrees C so that the surface area of the suspension changes twice each cycle. We have utilized this method to study the mechanisms involved in aggregate conversion. Several different surfactant preparations were analysed: (1) bovine natural surfactant, a sucrose-gradient purified material containing surfactant phospholipid and surfactant-associated proteins (SP-) SP-A, SP-B and SP-C; (2) bovine lipid-extract surfactant, which contains the surfactant phospholipids and SP-B and SP-C; (3) mixtures of dipalmitoyl phosphatidylcholine and phosphatidylglycerol (7:3, w/w) reconstituted with one or more surfactant proteins. Aggregate conversion was measured by phosphorus analysis of a 40,000 g supernatant (small aggregate) and pellet (large aggregates) before and after surface-area cycling. Surface-area cycling of lipid extract surfactant or lipids plus SP-B or SP-C resulted in rapid aggregate conversion. Lipids alone were not converted. Only a small percentage of purified natural surfactant was converted into small aggregates. Addition of SP-A to lipid extract surfactant could inhibit aggregate conversion of this material, but this was only observed when an additional 1% (w/w) of SP-B was added to the lipid extract. It is concluded that SP-A is important for large-aggregate integrity. It appears that SP-A acts in conjunction with SP-B. The presence of SP-B and/or SP-C is required for aggregate conversion; it is proposed that this reflects the necessity for lipid adsorption in aggregate conversion. PMID- 8002957 TI - Incorporation of fatty acids by concanavalin A-stimulated lymphocytes and the effect on fatty acid composition and membrane fluidity. AB - The fatty acid compositions of the neutral lipid and phospholipid fractions of rat lymph node lymphocytes were characterized. Stimulation of rat lymphocytes with the T-cell mitogen concanavalin A resulted in significant changes in the fatty acid composition of both neutral lipids and phospholipids (a decrease in the proportions of stearic, linoleic and arachidonic acids and an increase in the proportion of oleic acid). Membrane fluidity was measured using nitroxide spin label e.s.r., and increased during culture with concanavalin A. Culturing the lymphocytes in the absence of mitogen did not affect fatty acid composition or membrane fluidity. The uptake and fate of palmitic, oleic, linoleic and arachidonic acids were studied in detail; there was a time-dependent incorporation of each fatty acid into all lipid classes but each fatty acid had a characteristic fate. Palmitic and arachidonic acids were incorporated principally into phospholipids whereas oleic and linoleic acids were incorporated in similar proportions into phospholipids and triacylglycerols. Oleic acid was incorporated mainly into phosphatidylcholine, palmitic and linoleic acids were incorporated equally into phosphatidylcholine and phosphatidylethanolamine, and arachidonic acid was incorporated mainly into phosphatidylethanolamine. Supplementation of the culture medium with particular fatty acids (myristic, palmitic, stearic, oleic, linoleic, alpha-linolenic, arachidonic, eicosapentaenoic or docosahexaenoic acid) led to enrichment of that fatty acid in both neutral lipids and phospholipids. This generated lymphocytes with phospholipids differing in saturated/unsaturated fatty acid ratio, degree of polyunsaturation, index of unsaturation and n - 6/n - 3 ratio. This method allowed the introduction into lymphocyte phospholipids of fatty acids not normally present (e.g. alpha linolenic) or usually present in low proportions (eicosapentaenoic and docosahexaenoic). These three n - 3 polyunsaturated fatty acids replaced arachidonic acid in lymphocyte phospholipids. Fatty acid incorporation led to an alteration in lymphocyte membrane fluidity: palmitic and stearic acids decreased fluidity whereas the unsaturated fatty acids increased fluidity. It is proposed that the changes in lymphocyte phospholipid fatty acid composition and membrane fluidity brought about by culture in the presence of polyunsaturated fatty acids are responsible for the inhibition of lymphocyte functions caused by these fatty acids. PMID- 8002959 TI - Inhibition of prolyl 4-hydroxylase by oxalyl amino acid derivatives in vitro, in isolated microsomes and in embryonic chicken tissues. AB - The potency of oxalyl amino acid derivatives as inhibitors of prolyl 4 hydroxylase was studied in vitro, in isolated microsomes and in chicken embryonic tissue culture. These compounds represent structural analogues of 2-oxoglutarate in which the -CH2- moiety at C-3 is replaced by -NH-, with or without further structural modifications. The most efficient inhibitor of purified prolyl 4 hydroxylase was oxalylglycine. Its mode of inhibition was competitive with respect to 2-oxoglutarate. The Ki value varied between 1.9 and 7.8 microM, depending on the variable substrate used. Oxalylalanine inhibited purified enzyme with a Ki of 40 microM. Other oxalyl amino acid derivatives showed little inhibitory activity. In microsomes isolated from embryonic chicken bone, oxalylglycine and oxalylalanine inhibited prolyl hydroxylation with IC50 values of 23 and 120 microM respectively. Dimethyloxalylglycine was not an inhibitor of purified prolyl 4-hydroxylase and only weakly active in the microsomal system, but efficiently suppressed hydroxyproline synthesis in embryonic chicken calvaria and lung. The data suggest that dimethyloxalyl amino acids are converted into active inhibitors in intact cells, most likely in the cytoplasmic compartment. PMID- 8002960 TI - NADPH binding and control of catalase compound II formation: comparison of bovine, yeast, and Escherichia coli enzymes. AB - 1. NADPH binds to bovine catalase and to yeast catalases A and T, but not to Escherichia coli catalase HPII. The association was demonstrated using chromatography and fluorimetry. Bound NADPH fluoresces in a similar way to NADPH in solution. 2. Bound NADPH protects bovine and yeast catalases against forming inactive peroxide compound II either via endogenous reductant action or by ferrocyanide reduction during catalytic activity in the presence of slowly generated peroxide. 3. Bound NADPH reduces neither compound I nor compound II of catalase. It apparently reacts with an intermediate formed during the decay of compound I to compound II; this postulated intermediate is an immediate precursor of stable compound II either when the latter is formed by endogenous reductants or when ferrocyanide is used. It represents therefore a new type of hydrogen donor that is not included in the original classification of Keilin and Nicholls [Keilin, D. and Nicholls, P. (1958) Biochim. Biophys. Acta 29, 302-307] 4. A model for NADPH action is presented in which concerted reduction of the ferryl iron and of a neighbouring protein free radical is responsible for the observed NADPH effects. The roles of migrant radical species in mammalian and yeast catalases are compared with similar events in metmyoglobin and cytochrome c peroxidase reactions with peroxides. PMID- 8002961 TI - Human leucocyte glycosylasparaginase is an alpha/beta-heterodimer of 19 kDa alpha subunit and 17 and 18 kDa beta-subunit. AB - Human lysosomal glycosylasparaginase (AGA; EC 3.5.1.26) consists of two glycosylated subunits, alpha and beta. Treatment with 3% SDS at 45 degrees C as part of a new purification scheme did not affect enzyme activity, but the alpha subunit migrated an apparent 19 kDa peptide on SDS/PAGE instead of as a 24 kDa peptide, as observed without this SDS treatment. The N-terminal sequence was similar to that of the 24 kDa form, and, after reversed-phase h.p.l.c., the 19 kDa form was transformed to an apparent 24 kDa peptide on SDS/PAGE, indicating that their primary structures were identical. As the molecular mass of the alpha subunit deduced from its cDNA was 19.5 kDa, the variation might be due to incomplete SDS coating of the 24 kDa form. This was confirmed by the tendency of the 24 kDa variant to polymerize even in the presence of SDS. The molecular mass of the beta-subunit was 17 and 18 kDa in accordance with previous reports. Chemical cross-linking with 1-ethyl-3-(3-dimethylaminopropyl)carbodi-imide resulted in the appearance of a 38 kDa peptide on SDS/PAGE which reacted with both the subunit-specific antisera on Western-blot analysis. On SDS/PAGE at pH 10.2 the active enzyme migrated as an apparent 43 kDa peptide. These results indicate that native human glycosylasparaginase is a heterodimer. PMID- 8002962 TI - Role of dimerization in the control of the functioning of the human haemoglobin mutant haemoglobin Howick (beta 37 Trp-->Gly). AB - Haemoglobin Howick shows a high oxygen affinity (p50 = 1 mmHg) and a low co operativity (n = 1.3). Equilibrium studies show the protein to be essentially totally dimeric in the oxygenated form. A wide range of rapid kinetic experiments indicate that the deoxygenated form of the protein exists in a tetramer<-->dimer equilibrium with an associated equilibrium constant of 3 microM. These kinetic data also indicate that the oxygenated form of the protein exists in a tetramer<- >dimer equilibrium with an associated equilibrium constant of 35 mM, and furthermore clearly identifies a large increase in the rate of the tetramer-to dimer dissociation process as the origin of the vastly increased dissociation equilibrium constants. Simulations of the protein-concentration-dependence of the oxygen-binding properties of haemoglobin Howick, based on the measured equilibrium parameters, closely fits the experimental data. The change in dimerization constant for the deoxygenated form of the protein corresponds remarkably well to the free-energy change predicted for the simple transfer of the amino acid side chain at position beta 37 from a hydrophobic to a hydrophilic environment during the dimerization process. PMID- 8002963 TI - Novel inducible antibacterial peptides from a hemipteran insect, the sap-sucking bug Pyrrhocoris apterus. AB - Insects belonging to the recent orders of the endopterygote clade (Lepidoptera, Diptera, Hymenoptera and Coleoptera) respond to bacterial challenge by the rapid and transient synthesis of a battery of potent antibacterial peptides which are secreted into their haemolymph. Here we present the first report on inducible antibacterial molecules in the sap-sucking bug Pyrrhocoris apterus, a representative species of the Hemiptera, which predated the Endoptergotes by at least 50 million years in evolution. We have isolated and characterized from immune blood of this species three novel peptides or polypeptides: (i) a 43 residue cysteine-rich anti-(Gram-positive bacteria) peptide which is a new member of the family of insect defensins; (ii) a 20-residue proline-rich peptide carrying an O-glycosylated substitution (N-acetylgalactosamine), active against Gram-negative bacteria; (iii) a 133-residue glycine-rich polypeptide also active against Gram-negative bacteria. The proline-rich peptide shows high sequence similarities with drosocin, an O-glycosylated antibacterial peptide from Drosophila, and also with the N-terminal domain of diptericin, an inducible 9 kDa antibacterial peptide from members of the order Diptera, whereas the glycine-rich peptide has similarities with the glycine-rich domain of diptericin. We discuss the evolutionary aspects of these findings. PMID- 8002964 TI - Activation of rat brain ornithine decarboxylase by GTP. AB - The activity of ornithine decarboxylase (ODC) measured in different regions of rat brain was highest in the hippocampus and lowest in the cerebellum. The ODC activity of a crude extract of the cerebellum was increased by the addition of GTP to the enzyme assay. Following dissociation of the ODC-antizyme complex by Sephadex G-75 chromatography in buffer containing 0.25 M NaCl, the GTP activatable ODC was found in every brain region analysed. This GTP-activatable brain ODC has greater affinity for antizyme than the non-GTP-activatable brain ODC or the kidney ODC. The irreversible inhibitor of ODC, alpha difluoromethylornithine (DFMO), inhibited approx. 60% of the ODC activity of all brain regions, whereas kidney ODC was inhibited totally by DFMO. When extracts of brain and kidney were incubated at 55 degrees C, kidney ODC was rapidly inactivated, but brain ODC was more heat-stable. Brain ODC, but not kidney ODC, was activated by GTP and ATP, and also by their deoxy forms. The K1/2 for activation of the enzyme was 2 microM for GTP and 40 microM for ATP. Using partially purified brain ODC, the activation by GTP was irreversible. These results demonstrate for the first time that the GTP-activatable ODC exists in the brain and is associated with the antizyme. The possible mechanisms of activation by GTP, the significance of this finding for the regulation of brain ODC, and the similarities to and differences from the GTP-activatable ODC found in certain rodent and human tumours are all discussed. PMID- 8002965 TI - Expression of liver carnitine palmitoyltransferase I and II genes during development in the rat. AB - The enzyme activity and the expression (protein and mRNA concentrations) of genes encoding for hepatic carnitine palmitoyl-transferases (CPT) I and II were studied during neonatal development, in response to nutritional state at weaning and during the fed-starved transition in adult rats. The activity, the protein concentration and the level of mRNA encoding CPT I are low in foetal-rat liver and increase 5-fold during the first day of extra-uterine life. The activity and gene expression of CPT I are high during the entire suckling period, in the liver of 30-day-old rats weaned at 20 days on to a high-fat diet and in the liver of 48 h-starved adult rats. The activity and CPT I gene expression are markedly decreased in the liver of rats weaned on to a high-carbohydrate diet. By contrast, the activity, the protein concentration and the level of mRNA encoding CPT II are already high in the liver of term foetuses and remain at this level throughout the suckling period, irrespective of the nutritional state of the animals either at weaning or in the adult. PMID- 8002968 TI - On the structure/function relationship of polymorphonuclear-leucocyte collagenase. PMID- 8002967 TI - Cloning and expression in Bacillus subtilis of the npr gene from Bacillus thermoproteolyticus Rokko coding for the thermostable metalloprotease thermolysin. AB - We report the isolation, cloning and expression, in Bacillus subtilis, of the gene coding for thermolysin, a thermostable metalloprotease which is produced by Bacillus thermoproteolyticus Rokko. The nucleotide sequence has revealed that, like neutral proteases produced by other members of the Bacillus species, thermolysin is probably produced as a preproenzyme carrying a typical N-terminal membrane signal sequence. Further, the thermolysin gene shares a strong homology with two other previously cloned genes from two different strains of Bacillus stearothermophilus. The sequence of the mature secreted protease, inferred from the DNA sequence, is, with two exceptions, identical with the previously published protein sequence of thermolysin [Titani, Hermodson, Ericsson, Walsh and Neurath (1972) Nature (London) 238, 35-37]. The exceptions are Asn37 and Gln119, originally reported to be Asp and Glu respectively. The biochemical characterization of the secreted recombinant protein shows that it is indistinguishable from the wild-type thermolysin. PMID- 8002966 TI - A caffeine- and ryanodine-sensitive intracellular Ca2+ store can act as a Ca2+ source and a Ca2+ sink in PC12 cells. AB - We have investigated the modulation of stimulus-induced changes in intracellular Ca2+ concentration ([Ca2+]i) by a caffeine-and ryanodine-sensitive Ca2+ store in PC12 cells. In populations of fura-2-loaded cells, caffeine cause a concentration dependent increase in [Ca2+]i that was saturable, reversible and inhibited in a use-dependent fashion by ryanodine. Maximal Ca2+ release occurred with 40 mM caffeine, with an EC50 of 13 mM caffeine and a Hill coefficient (h) of 2.7, indicating that the release mechanism was co-operative. Pretreatment of intact cell populations with increasing concentrations of caffeine in nominally Ca(2+) free medium inhibited the subsequent Ca2+ response to a maximal concentration of ATP, in a dose-dependent manner. In permeabilized cells, a maximal concentration (40 microM) of InsP3 still released Ca2+ in the presence of a supramaximal concentration (50 mM) of caffeine, whereas caffeine was unable to release Ca2+ after the InsP3-sensitive store had been completely emptied. These data suggest that PC12 cells contain a uniquely InsP3-sensitive Ca2+ store, and a store that is sensitive to both InsP3 and caffeine. Depletion of the caffeine-sensitive Ca2+ store by caffeine and ryanodine pretreatment in intact cells attenuated the Ca2+ response to ATP, but not to 55 mM K+, suggesting that the caffeine-sensitive Ca2+ store acts as a Ca2+ source after ATP stimulation, but not after depolarization with 55 mM K+. Pretreatment of intact cells with ATP and ryanodine resulted in a use-dependent block of both caffeine- and ATP-mediated Ca2+ release, confirming that ATP stimulation of PC12 cells brings about activation of ryanodine receptors. The rate of recovery, but not the magnitude or rate of onset, of the depolarization-induced [Ca2+]i transient was modulated by the state of filling of the caffeine-sensitive Ca2+ store such that recovery was prolonged if the store was either full, or empty and unable to refill. We conclude that the caffeine- and ryanodine-sensitive Ca2+ store can act as a Ca2+ source and a Ca2+ sink in PC12 cells, and that its role may in part be governed by the nature of the stimulating agent. PMID- 8002969 TI - Protochlorophyllide reductase is homologous to human carbonyl reductase and pig 20 beta-hydroxysteroid dehydrogenase. PMID- 8002970 TI - Antibodies elicited by the primary response are useful as ligands for immunoaffinity chromatography. AB - A suitable antibody for immunoaffinity chromatography is considered to efficiently bind the antigen in the adsorption step and to dissociate the bound antigen with mild changes in the environmental conditions. To develop an effective method for preparing such antibodies, murine antisera elicited by the primary and secondary responses against bovine beta-lactoglobulin, a model protein antigen, were examined and compared for their ability to bind the antigen under differing pH and ionic strength conditions. Antibodies from the primary response were usually found to be highly sensitive to changes in pH and ionic strength, suggesting that these antibodies may be useful as ligands for immunoaffinity chromatography. PMID- 8002971 TI - Oxidized low density lipoprotein increases U937 cell 5-lipoxygenase activity: induction of 5-lipoxygenase activating protein. AB - This study examines the effects of oxidized low density lipoprotein (ox-LDL) on mononuclear cell arachidonic acid (AA) metabolism. U937 and HL60 cells, employed as models for mononuclear cells and promyelocytic cells, respectively, were exposed to ox-LDL (20 micrograms protein/ml) for 24 hours. HPLC analysis of 1-14C AA metabolites indicates that ox-LDL increases U937 and HL60 cell production of 15-hydroxyeicosatetraenoic acid (15-HETE) and 5-hydroxyeicosatetraenoic acid (5 HETE). Northern analysis indicates that ox-LDL increases U937 cell FLAP transcript levels 10-times control levels but did not appear to alter 5 lipoxygenase (5-LO) mRNA levels. In contrast, ox-LDL increases HL60 cell transcript levels for FLAP and 5-LO 1.5 times and 10 times control levels, respectively. Thus, we propose that ox-LDL plays an important role in the up regulation of the 5-LO pathway in mononuclear cells. Such activation may explain, in part, the mechanisms by which ox-LDL promotes atherogenesis. PMID- 8002972 TI - cDNA cloning and expression of Cry j II the second major allergen of Japanese cedar pollen. AB - We have isolated and sequenced a cDNA clone coding for Cry j II, the second major allergen of Japanese cedar (Cryptomeria japonica) pollen. A 1.7-kilobase cDNA clone contained an open reading frame coding for a 514-amino acid protein, including a putative signal peptide of 54 amino acid and three potential glycosylation sites. The deduced amino acid sequence of the Cry j II shows significant identities to those of the polygalacturonases associated with fruit ripening in tomato (40%) and avocado (43%) and found in pollen of maize (34%). Cry j II cDNA product expressed in E. coli was recognized by human IgE from patients suffering from cedar pollinosis, suggesting that recombinant Cry j II might be used as an allergen for the clinical diagnosis of cedar pollinosis. PMID- 8002974 TI - In vivo pharmacokinetics of nitroxides in mice. AB - The in vivo reduction kinetics of twenty different nitroxide compounds in mice has been investigated by using an electron paramagnetic resonance (EPR) spectrometer, equipped with an S-band loop-gap resonator, operating at 3.5 GHz. The diameter of the resonator (4 mm) fits well the tip of the mouse tail, thus allowing the direct detection of in vivo free radicals in the blood circulation. After intravenous injection, the nitroxide signal in the circulation of the mouse tail was followed with time; no anesthetic agent was used. For the pyrrolidine nitroxides (five-member rings) with different functional groups, the t1/2 values followed the order: = O > COO- > OH > CONH2 approximately CH2NH2 > NH2. A different trend was obtained for the piperidine nitroxides (six-member rings): COO- > CH2NH2 > OH approximately NH2 > CONH2 > = O. The most striking observation was that while the t1/2 value of the cabonyl pyrrolidine is the longest among all the nitroxides tested for this property, that of the carbonyl piperidine is the shortest. Comparison of the in vivo decay kinetics of six pairs of pyrrolidine nitroxides and piperidine nitroxides with same functional groups showed that the t1/2 values of the former are 2 to 28 times longer than the latter. It is concluded here that the pyrrolidine nitroxides are more resistant to cellular metabolism in vivo when compared to the piperidine nitroxides. PMID- 8002973 TI - Adrenoleukodystrophy gene encodes an 80 kDa membrane protein. AB - An antibody against the synthetic C-terminal peptides deduced from the cDNA of the gene responsible for X-linked adrenoleukodystrophy (ALD) was produced to characterize the product of the ALD gene. The antibody reacted with the 80 kDa band protein in control fibroblasts, while no bands were detected in the fibroblasts from a patient with ALD (#163), in which mRNA of the ALD gene was undetectable based on Northern blot analysis. The 293T cells transfected with the full-coding cDNA inserted in the expression vector produced a new 80 kDa protein, as detected by Western blot. In an immunocytological study, the staining was in a punctate pattern, in the normal fibroblasts. However, there was no punctate staining in the #163 cells. These data thus indicate that the ALD gene encodes an 80 kDa membrane protein. PMID- 8002975 TI - Phospholipase C-gamma 1 is present on the surface of human colorectal cancer cells. AB - Using murine monoclonal antibodies, we have detected the novel signal transducing enzyme, phospholipase C-gamma 1, on the surface of cultured human colorectal cancer cells. We have also demonstrated the presence of this enzyme on the surface of fresh human tumor cells derived from primary and metastatic colorectal tumors. This enzyme has previously been described to be associated only with the inner face of the plasma membrane and the cell cytosol. The finding of an enzyme critical to the signal transduction pathway may have important implications for additional functions of this protein. PMID- 8002976 TI - The rat, mouse, and human genes encoding the receptor for parathyroid hormone and parathyroid hormone-related peptide are highly homologous. PMID- 8002977 TI - The effect of sulfite on the ATP hydrolysis and synthesis activity of membrane bound H(+)-ATP synthase from various species. AB - The action of sulfite on ATP hydrolysis and synthesis activities is investigated in membrane vesicles prepared from the cyanobacterium Synechococcus 6716, chromatophores from the photosynthetic purple bacterium Rhodospirillum rubrum, membrane vesicles from the related non-photosynthetic bacterium Paracoccus denitrificans, and bovine heart submitochondrial particles. Without any further pretreatment ATP hydrolysis is stimulated by sulfite in all four membrane preparations. Typically ATP synthesis in the cyanobacterial membrane vesicles is inhibited by sulfite, whereas ATP synthesis in chromatophores and the submitochondrial particles is not. These differences in sensitivity of ATP synthesis to sulfite, however, correspond well with the distribution of (photosynthetic) sulfur oxidizing pathways in the remaining three organisms/organelles compared in this study. PMID- 8002978 TI - Mouse macrophage derived monocyte chemotactic protein-3: cDNA cloning and identification as MARC/FIC. AB - When the mouse macrophage cell line WEHI-3 is triggered with LPS it produces proteases and secondary cytokines including interleukin-6 and chemokines. In an attempt to isolate the mouse homologue of the human monocyte chemotactic protein 3 (MCP-3), a cDNA library from LPS-stimulated WEHI-3 cells was screened with the full-size human MCP-3 cDNA. The longest cDNA out of several positive clones was sequenced and encoded a protein of 97 residues. Except for a third codon letter mismatch it was identical to the mouse MARC cDNA and encoded the MARC protein. The murine Fic cDNA, which encodes a Marc-mutant protein with an arginine substitution for alanine, was not identified in the other sequenced homologous isolates. Similar to the human system, in which MCP-3 is most related to MCP-1, MURINE MCP-3 was found to be more homologous to mouse MCP-1/JE than to other murine C-C chemokines. We therefore postulate that MARC/FIC is the mouse MCP-3. PMID- 8002979 TI - Apoptosis of human adipocytes in vitro. AB - Large increases in fat stores involve an increase in adipocyte number via the replication and differentiation of preadipocytes, with the resultant cell gain widely regarded as irreversible. To date, there has been no clearly defined process or mechanism reported by which adipocyte deletion may occur. Here, we show that human adipocytes undergo apoptosis following growth factor deprivation or mild heat injury in vitro, thus demonstrating a cellular mechanism by which normal adipocyte loss could occur in vivo. The findings have implications for the understanding of adipose tissue kinetics and its derangement as well as for the potential development of methods for modifying fat store size. PMID- 8002980 TI - Adenosine acts as an endogenous activator of the cellular antioxidant defense system. AB - Oxygen free radicals have been implicated in the pathogenesis of ischemic cell injuries. These free radicals are normally scavenged by antioxidant enzymes. Adenosine is normally released during ischemia and protects against ischemic injuries by interacting with adenosine receptors (ARs). The mechanism underlying its cytoprotective action is unclear. In this report, we provide evidence that activation of a unique A3AR in rat basophilic leukemia cells (RBL-2H3) leads to a 2 to 3 fold increase in activity of superoxide dismutase, catalase and glutathione peroxidase and also increases in the activity of glutathione reductase. Similar increases in enzyme activity were elicited in bovine and human endothelial cells, rat cardiac myocytes and smooth muscle cells. Increases in enzyme activity were attenuated by theophylline (an antagonist of the A3AR) and by pertussis toxin, implicating a role of A3AR/Gi protein in the activation. Importantly, activation of the A3AR decreased the degree of lipid peroxidation in these cells. These data provide strong evidence that the cytoprotective action of adenosine during ischemic cell injuries is mediated, at least in part, via a novel mechanism-activation of the cellular antioxidant enzymes. PMID- 8002981 TI - Reconstitution of the isobutene-forming reaction catalyzed by cytochrome P450 and P450 reductase from Rhodotorula minuta: decarboxylation with the formation of isobutene. AB - An isobutene-forming activity was reconstituted with cytochrome P450rm and cytochrome P450 reductase purified from Rhodotorula minuta. The nonionic detergent. Emulgen 911, present in the preparation of purified P450rm, inhibited the reconstitution. Bovine serum albumin enhanced the activity of the reconstituted system. Branching of the beta carbon of the substrate carboxylic acid was important for formation of isobutene. In a comparative study with isovalerate and 3-deuterio-3-methylbutanoate, a very large isotopic effect (kH/kD = 14) was observed. This result indicates that formation of isobutene might be initiated by abstraction of hydrogen from the beta carbon of isovalerate and might be followed by decarboxylation. PMID- 8002982 TI - Mutation of aspartate residues in the third extracellular loop of the rat B2 bradykinin receptor decreases affinity for bradykinin. AB - Two aspartates in the third extracellular loop of the rat B2 bradykinin (BK) receptor have been implicated as important residues for agonist binding. Asp268 and Asp286 were mutated to alanine residues and changes in agonist and antagonist binding affinity were examined. The IC50 value for BK as a competitor of [3H] NPC 17731 binding to the rat wild type receptor was 1.1 nM, while the Ala268 and Ala286 receptor mutants exhibited IC50 values of 19 nM and 28 nM, respectively. The Ala268Ala268 receptor mutant exhibited an IC50 for BK of 500 nM. These mutations had little effect on binding affinity when NPC 17761, a BK antagonist, was used to compete [3H] NPC 17731 binding. Electrophysiological examination of Xenopus oocytes expressing wild type or Ala268 Ala286 receptors confirmed the importance of the Asp268 and Asp286 residues for BK recognition. BK activated the mutant receptor with comparable efficacy relative to the wild type receptor, but a 1750-fold reduction in potency was observed. PMID- 8002983 TI - Identification and possible localization of cGMP-dependent protein kinase in bovine aortic endothelial cells. AB - Endothelial-derived nitric oxide (NO) is an important intercellular messenger. Although endothelial cells contain both nitric oxide synthase and soluble guanylate cyclase, the nature of receptor proteins for cGMP is uncertain. Based on previous work in vascular smooth muscle cells which indicates that the cGMP dependent protein kinase (cGK) is partially associated with the cytoskeleton, we determined that cGK was present in non-cytosolic fractions of endothelial cells. The data reveal that cGK is found only in Triton-soluble extracts of particulate fractions from bovine aortic endothelial cells and provide the first evidence for the existence of cGK in this cell type based on immunoreactivity, immunofluorescence microscopy and phosphotransferase activity. The limited distribution of endothelial cell cGK may explain why this kinase has not been heretofore identified in endothelial cells. PMID- 8002984 TI - Isolation and characterization of vascular endothelial cells derived from mice lacking endothelin-1. AB - Microvascular endothelial cells were isolated from endothelin (ET)-1 knockout mice. The ET-1-lacking endothelial cells represent normal shape and activity of acetyl-LDL uptake. The growth of ET-1-lacking endothelial cells was not different from that of control cells in the presence of serum. Compensatory production of other ET isoforms does not occur in these cells. Conversion of big ET-1 to ET-1 is not different between ET-1-lacking and control cells. These results suggest that ET-1 is not essential to endothelial morphology and growth, that the expression of ET isoforms is not redundant in endothelial cells, and that the machinery processing ET-1 is preserved despite of the absence of its substrate. PMID- 8002985 TI - Effect of the order of antibody variable regions on the expression of the single chain HyHEL10 Fv fragment in E. coli and the thermodynamic analysis of its antigen-binding properties. AB - In order to physically stabilize the Fv fragment of anti-lysozyme monoclonal antibody, HyHEL10, the variable domains were linked covalently with a flexible linker. A marked difference in the level of expression in E. coli was observed between VH-linker-VL (scFvHL) and VL-linker-VH (scFvLH). The highly expressed scFvLH was purified by a single step of affinity chromatography from the culture supernatant with a typical yield of 3-5 mg per liter of culture. This HyHEL10 scFvLH showed reduced binding activity toward its antigen, HEL, in comparison with Fv. Thermodynamic study showed that this reduced activity was due to entropic loss upon binding to its antigen, although this interaction between scFvLH and its antigen was enthalpically favorable. PMID- 8002986 TI - The heat shock transcription factor in liver exists in a form that has DNA binding activity but no transcriptional activity. AB - The binding activity of the heat shock transcription factor (HSF) to the heat shock element (HSE) is observed in non-stressed liver and freshly isolated hepatocytes when the expression of hsp70 is undetectable. HSF binding activity in non-stressed liver/hepatocytes is specific for HSE and similar to the HSF binding activity observed in heat shocked hepatocytes that is associated with hsp70 transcription. However, the HSF binding activity in non-stressed and heat shock cells can be distinguished on the basis of the thermal stability in vitro. The HSE binding activity of cell extracts isolated from non-stressed liver/hepatocytes was lost rapidly when the extracts were incubated at 37 degrees C. In contrast, the HSF binding activity of cell extracts isolated from heat shocked hepatocytes was relatively stable at 37 degrees C. Based on our observations, we propose that the activation of HSF is a multistep process that involves a change in conformation after oligomerization and the acquisition of DNA binding to a form that is more thermostable and is associated with increased hsp70 transcription. PMID- 8002987 TI - Caffeine biotransformation in human hepatocyte lines derived from normal liver tissue. AB - Caffeine biotransformation was demonstrated in three novel human hepatocyte cell lines established from normal liver tissue and cultured continuously for 19 to 30 months. Caffeine and its metabolites were identified and quantified by high performance liquid chromatography. Without induction, caffeine was metabolized to the four primary metabolites [theobromine (37X), paraxanthine (17X), theophylline (13X), 1,3,7-trimethylurate (137U)]. Under these basal conditions 137U was the predominant metabolite. The actual pattern of metabolite production was a reproducible characteristic of each line. After induction with dibenz(a,h)anthracene, the formation of 17X was increased 4-17 fold. Induction with phenobarbital did not change the metabolic profile. These human hepatocyte lines can reproduce in vitro metabolism of caffeine observed in man in vivo. PMID- 8002988 TI - Translation initiation from non-AUG codons in COS1 cells is mRNA species dependent. AB - Sendai virus P/C mRNA, human erythrocyte membrane protein 4.1 mRNA and PDGF-B chain mRNA were used to test whether translation initiation from non-AUG codons in COS1 cells was mRNA species dependent. Site-directed mutants of the authentic translation start sites of these mRNAs to alternate start codons showed that while P/C mRNA is capable of initiating translation from non-AUG start sites the other two mRNAs are not. Our study shows that translation initiation from non-AUG codons is mRNA species dependent and suggests that higher order structure of an mRNA determines the non-AUG translation start site. PMID- 8002989 TI - Ki-ras and c-myc oncogene expression measured by coamplification polymerase chain reaction. AB - Ki-ras and c-myc oncogene mRNA in carcinoma tissue was quantitatively detected by the coamplification polymerase chain reaction. After the reverse transcription of the mRNA mixture with random hexanucleotide primer the coamplification polymerase chain reaction of the oncogene and the internal standard beta-actin cDNA was done. The amount of oncogene mRNA was calculated from the coamplified product ratio. Ki-ras expression in a human gastric cancer strain H-111 was estimated to 5 percent of beta-actin. The expression of c-myc mRNA in colorectal carcinoma tissue was observed to be ten to one hundred times higher than normal mucosa. Gene expression was compared numerically in mole/liter without using hybridization and radioactive probes. PMID- 8002991 TI - Multiple binding sites on the superantigen, staphylococcal enterotoxin B, imparts versatility in binding to MHC class II molecules. AB - To determine MHC class II molecule binding regions of staphylococcal enterotoxin B (SEB), we employed a structurally based approach in which eight overlapping peptides of the entire SEB molecule were synthesized to encompass discrete secondary structures based on the SEB crystalline structure. SEB peptides encompassing amino acid residues 1-33, 31-64 and 179-212 successfully competed with [125I]SEB for binding to DR1 transfected L cells. In contrast, SEB peptides encompassing amino acid residues 1-33, 124-154, 150-183 and 179-212 successfully competed with [125I]SEB for binding to Raji cells (HLA-DR3, DRw10, DQw1 and DQw2). In addition, the SEB peptide (124-154) inhibited the mitogenic function of SEB. Thus, we have identified multiple regions, including the C-terminus, of SEB that are involved in binding to MHC class II and have shown that these interactions are complex and dependent on the haplotype of the MHC class II molecule. PMID- 8002990 TI - Potent inhibition of CDC2 kinase activity by the flavonoid L86-8275. AB - L86-8275 [(-) cis-5,7-dihydroxy-2-(2-chlorophenyl)-8[4-(3-hydroxy-1- methyl) piperidinyl]-4H-benzopyran-4-one] directly inhibits immunoprecipitated Cdc2 kinase activity from G2/M synchronized MDA-MB-468 breast carcinoma cells and is at least 250-fold more potent than either quercetin or genistein. Purified sea star Cdc2 kinase (IC50 = 0.5 microM) was inhibited with a similar potency to immunoprecipitated Cdc2 kinase from MDA-MB-468 cells (IC50 = 0.4 microM). This inhibition was competitive with respect to ATP (KiATP = 0.041 microM) and noncompetitive with respect to a synthetic peptide substrate, CDK1S1 (AAKAKKTPKKAKK-CONH2, KiCDK1S1 = 0.14 microM). These data suggest L86-8275 as a lead structure for the development of inhibitors of the cyclin-dependent kinases. PMID- 8002992 TI - Potent transforming activity of the G13 alpha subunit defines a novel family of oncogenes. AB - The finding of GTPase inhibiting mutations in genes for alpha subunits of Gs and Gi2 in certain endocrine tumors suggests that heterotrimeric G proteins might contribute to neoplasia. Expression of these activated forms of alpha s or alpha i2 in NIH 3T3 murine fibroblasts induces certain alterations in cell growth, but is weakly transforming. Mutationally activated forms of the alpha subunit of another G protein family, Gq, are fully oncogenic in NIH 3T3 cells, although with a very low potency. In contrast, we have recently shown that overexpression of the alpha subunit of a novel G protein, G12, is itself transforming, and an activated mutant of alpha 12 behaves as one of the most potent oncogenes known. In this study, we have explored whether another member of the G alpha 12 family, G alpha 13, harbors transforming potential. Our data demonstrate that G alpha 13 can behave as a potent dominant acting oncogene. These findings strongly suggest that the G12 family of G proteins represents a novel class of oncogenes. PMID- 8002993 TI - The rat amyloid precursor protein promoter contains two DNA regulatory elements which influence high level gene expression. AB - We have investigated the transcriptional activity and regulatory elements of the rat amyloid precursor protein promoter. A DNA fragment containing 375 base pairs upstream of the start codon drives transcription in rat PC12 cells at a level greater than five-fold that of the SV40 promoter. This fragment contains a predominant transcription start point and several additional start points which are similar to those found in the human promoter. The strong promoter activity appears to be dependent upon two small DNA regulatory elements. Deletion of one element at positions -260 through -248 reduces activity by 85%. This is the first report of a positive regulatory element at this location. Deletion of a second element at positions -223 through -192 reduces activity by 30%. Gel mobility shift assays with nuclear extracts from whole rat brain suggest that nuclear proteins interact directly with the second element but not with the first one. PMID- 8002995 TI - Erythrocyte tropomodulin binds to the N-terminus of hTM5, a tropomyosin isoform encoded by the gamma-tropomyosin gene. AB - Tropomodulin is a 40.6-kDa protein that binds to one end of the rod-like tropomyosin and inhibits its cooperativity and binding to actin. In myofibrils, tropomodulin has been localized at or near the free end of thin filaments. Using recombinant and chimeric molecules in a solid-phase binding assay, we demonstrate that it is the N-terminus of tropomyosin that interacts with tropomodulin. Among several tropomyosin isoforms tested, hTM5 encoded by the human gamma-tropomyosin gene has the highest affinity toward human erythrocyte tropomodulin. Tropomodulin may, therefore, regulate the length and/or organization of actin filaments by differential binding to tropomyosin isoforms. hTM5 exists in the human erythrocyte membrane skeleton. In non-muscle cells, tropomodulin may block the head-to-tail association of tropomyosins and their interaction with actin at the pointed end of actin filaments by preferentially binding to TM5 at its N terminus. PMID- 8002994 TI - Identification of two distinct promoters in the chicken caldesmon gene. AB - Caldesmon (CaD) is a suitable molecular marker for phenotypic modulation of smooth muscle cells. Chicken CaD gene is composed of 17 exons with a whole length of 100-150 kilobases (kb). Exons 1a-1, 1a-2, and 1a-3 encode the 5'-terminal sequence specific to mRNA for gizzard type CaD, and exon 1b encodes the sequence specific to brain type CaD mRNA. Here, we have characterized the 5'-upstream regions of chicken CaD gene. Primer extension analysis revealed that the transcriptional starting sites of gizzard and brain CaD mRNAs were 218 and 279 nucleotides upstream from each translational initiation codon, respectively. We have identified two distinct promoters (gizzard type and brain type promoters) in the CaD gene by bacterial chloramphenicol acetyltransferase (CAT) assay using chick embryo fibroblasts (CEFs). The 5'-upstream region of exon 1a-1 showed remarkable promoter activity, but the activity of the 5'-upstream region of exon 1b was low (10% of the former). These results indicate that CaD subtypes are generated by differential RNA transcriptions. PMID- 8002997 TI - Dopamine inhibits TRH-induced MAP kinase activation in dispersed rat anterior pituitary cells. AB - We recently reported the existence of two separate pathways for thyrotropin releasing hormone (TRH)-induced mitogen-activated protein (MAP) kinase activation in GH3 pituitary tumor cells. To test the role of MAP kinase in TRH action, we examined the effect of dopamine (DA) on TRH-induced MAP kinase in primary cultures of rat anterior pituitary cells. 1 microM of DA attenuated 1 microM TRH induced MAP kinase activity and phosphorylation. 100 ng/ml of islet-activating protein (IAP) blocked these inhibitory effects of DA. These results suggest that crosstalk exists between the DA signaling pathway and the TRH-stimulated MAP kinase activating pathway in rat anterior pituitary cells. PMID- 8002996 TI - TFPACD, a novel bifunctional reagent for reacting with DCCD sites in proteins: studies using Escherichia coli ATP synthase. AB - A novel cross-linker, 1-[6-(4-azido-2,3,5,6-tetrafluorobenzamido)hexyl]-3 cyclohexylc arbodiimide (TFPACD), has been synthesized and tested by reaction with the Escherichia coli ATP Synthase (ECF1F0). The reagent has a carbodiimide as one reactive group, which is shown to react with ECF1F0 in a similar way to 1,3-dicyclohexylcarbodiimide (DCCD) and modify the beta subunit of the ECF1 part and the c subunit of the F0 part. Reaction with both the ECF1 and F0 parts of the complex inhibited ATPase activity. The second reactive group in the reagent is the photoactivatable tetrafluorophenylazide moiety. Subsequent UV photolysis of TFPACD--modified ECF1 and ECF1F0 led to generation of cross-linked products in significant yields, one between beta and alpha subunits; the second, dimers of the c subunit of the F0 part. PMID- 8002998 TI - Expression of TGF-beta s and TGF-beta type II receptor mRNAs in mouse folliculogenesis: stored maternal TGF-beta 2 message in oocytes. AB - The present in situ hybridisation study describes expression of TGF-beta 1, TGF beta 2, TGF-beta 3, and TGF-beta type II receptor mRNA during follicular development, and the temporal pattern and abundance of TGF-beta 2 transcripts in early pre-implantation embryos. TGF-beta 1 hybridisation signals were most prominent in the outer granulosa cell layers of the post-antral follicles and in the corpus luteum, whereas strong expression of TGF-beta type II receptor mRNA was confined to thecal cells. Weak TGF-beta 3 mRNA expression was observed in all major cell types of pre- and post-antral follicles. Most notably, the very strong TGF-beta 2 hybridisation signals which were detected in developing oocytes declined rapidly following fertilization. Although still abundant in two-cell embryos, TGF-beta 2 hybridisation signals were barely detectable in four- and eight-cell embryos. These findings, and the presence of specific sequence motifs in the 3' untranslated region of TGF-beta 2 mRNAs, suggest that TGF-beta 2 transcripts are stored as maternal messages. PMID- 8002999 TI - Expression of matrilysin mRNA in colorectal adenomas and its induction by truncated fibronectin. AB - Matrilysin is believed to have a role in tumor progression. Its expression correlates with the occurrence of colorectal cancer. We have examined the expression of matrilysin mRNA in various colorectal disorders and its localization using RT-PCR and in situ hybridization. We have also examined whether Matrilysin is induced by cell to matrix interaction. Matrilysin mRNA was detected in all adenoma tissues examined, whereas none was detectable in hyperplastic polyps, mildly inflamed regions of ulcerative colitis or normal colon tissues, and its message was localized in adenoma cells themselves. In addition, levels of enzyme activities of matrilysin were lower in adenomas compared with cancers in casein zymography. Matrilysin mRNA was induced by immobilized truncated fibronectin or RGD peptide. Thus, matrilysin may play an important role in colorectal carcinogenesis. PMID- 8003000 TI - Kinetin delays the onset of ageing characteristics in human fibroblasts. AB - Kinetin (Kn) is a synthetic cytokinin plant growth hormone having some senescence retarding effects in plants. Its effects on animal cells have been, until now, best considered as growth inhibitory and anti-tumorigenic. However, we have observed that an addition of 40-200 microM Kn in the culture medium of human diploid fibroblasts can both delay the onset and decrease the extent of many of the ageing characteristics that appear during serial passaging of normal cells in culture. Age-related changes that are affected by Kn include morphological alterations, growth rates, cell size, cytoskeletal organisation, macromolecular synthesis and the intensity of autofluorescence due to the oxidative damage product lipofuscin. These anti-ageing effects of Kn are achieved without any increase in the cell culture lifespan in terms of maximum proliferative capacity in vitro. PMID- 8003001 TI - Growth inhibition of SV40-transformed human keratinocytes by TGF-beta s is not linked to dephosphorylation of the Rb gene product. AB - We found that transforming growth factor beta 1 (TGF-beta 1) and TGF-beta 2 inhibited the growth of normal human keratinocytes and their SV40-transformed counterpart in a dose dependent manner. Both normal and SV-40 transformed keratinocytes accumulated in G1 when treated with TGF-beta s. The hyperphosphorylated form of Rb gene product (RB) was reduced by TGF-beta s in normal keratinocytes. In contrast, phosphorylation of RB was not essentially affected in SV-40 transformed cells. This uncoupling of growth kinetics and phosphorylation states of RB in SV-40 transformed keratinocytes suggests that RB is not the primary target of action for TGF-beta s and that additional factors or pathways may be involved in mechanisms of the growth inhibition. PMID- 8003002 TI - Ubiquitin gene expression in skeletal muscle is increased by tumour necrosis factor-alpha. AB - An acute intravenous administration of 100 micrograms/kg body weight of recombinant tumour necrosis factor-alpha resulted in a time-dependent increase in the levels of ubiquitin mRNAs in rat skeletal muscle. The results presented here, together with previous observations demonstrating that the cytokine increases the conjugation of proteins with ubiquitin in rat skeletal muscle (1), suggest that the ubiquitin system for non-lysosomal protein degradation could have a very important role in the mechanism triggered by tumour necrosis factor-alpha which is responsible for enhanced muscle proteolysis in sepsis and other pathological states. PMID- 8003003 TI - Dimaprit analogues inhibit tyrosinase via a disulphide breakdown product independently of the histamine H2 receptor. AB - Histamine displayed specific and saturable binding to membrane fractions of the human melanoma cell line MM96E (Kd = 72.4 nM and Bmax = 487 fmol/mg protein). There was weak competition with isothioureas that inhibit tyrosinase in intact cells: dimaprit (an H2 agonist) nordimaprit and S-[2-(N,N diisopropyl)ethyl]isothiourea (DINOR). Under culture conditions, rapid, pH dependent hydrolysis of the isothioureas occurred, with cleavage to urea and a thiol which spontaneously oxidised to the disulphide. The H3 agonist imetit, which also inhibited tyrosinase, behaved similarly. The disulphide breakdown product of DINOR but not the thiol inhibited tyrosinase activity in intact MM96E cells to a similar extent as DINOR itself. Isothioureas with more bulky substituents, however, were stable in culture and did not inhibit tyrosinase. The results show that (a) certain histaminergic drugs exert effects via a disulphide hydrolysis product independently of the histamine H2 receptor, and (b) beta aminoethyldisulphides are depigmenting agents. PMID- 8003004 TI - Baculovirus mediated high level expression of human placental aromatase (CYP19A1). AB - An efficient expression system for a cDNA clone of human placental aromatase has been developed using the baculovirus expression system in TN5 (Tricoplusia ni) cells. The protein was expressed at high levels, with specific aromatase activity and specific P450 content comparable to that found in human placental microsomes. To achieve these high levels of activity, hemin had to be added to the cultures of infected cells and NADPH-cytochrome P450 reductase had to be included in the assay buffer. The spectral properties of ligand bound forms of the baculovirus expressed aromatase were very similar to those exhibited by the same ligand bound forms of the enzyme purified from placental microsomes. This expression system appears to be a suitable source for the purification of milligram quantities of recombinant aromatase. PMID- 8003005 TI - Genetic tests to reveal TAT homodimer formation and select TAT homodimer inhibitor. AB - The HIV Tat protein is essential for productive infection and is a potent activator of viral gene expression. By constructing a genetic fusion between the amino-terminal DNA-binding domain of the lambda repressor (as a reporter for dimerization) and Tat, we show that Tat forms dimers in vivo. By deletion analysis and site-directed mutagenesis, we show that (i) the peptide encoded by exon-1 of Tat is sufficient to promote dimerization and (ii) cys37 is essential for homo-dimerization of Tat protein. Furthermore, by using a new E. coli strain in which the expression of beta-galactosidase is under the negative control of the cl::Tat repressor, we select a protein (CD10/Nep) expressed by human Jurkat T cells which inhibits Tat dimerization. PMID- 8003006 TI - The interpretation of the time-resolved fluorescence anisotropy of diphenylhexatriene-phosphatidylcholine using the compound motion model. AB - Time-resolved fluorescence anisotropy experiments on lipid membranes can provide estimates of the molecular order and motion on microscopic scales. For the analysis of anisotropy data the so-called compound motion model was recently introduced to overcome problems with conventional models. We show that this novel model gives good fits for the time-resolved anisotropy of the fluorescent probe diphenylhexatriene-phosphatidylcholine (DPHPC) and can be successfully used to interpret experiments with DPHPC embedded in small unilamellar vesicles of the lipids DMPC, POPC, DOPC, DLPC, DERPC, DOPE, POPE, EGGPG and SQDG. The lifetime and order parameters are found to be intermediate between those found for the related DPH and TMA-DPH fluorescent probes, while the rotational diffusion of DPHPC is much slower. These findings can be rationalised in terms of the position of the DPH-fluorophore of DPHPC in the bilayer. PMID- 8003007 TI - Proteolytic degradation of microtubule associated protein tau by thrombin. AB - Deposits in the brain of beta-amyloid and tau proteins constitute the two major characteristics of Alzheimer's disease. It is unknown how the deposits are formed, but several studies have suggested that proteases might play a crucial role. Consequently, the search for proteases responsible for processing tau and amyloid precursor protein has become relevant. Here, the ability of thrombin to process tau in vitro is examined. Thrombin, which is found in blood but presumably also in the nervous system, cleaves tau and generates a stable 25 kDa fragment. Immunoblot and amino acid sequencing reveals that the fragment is derived from the C-terminal of tau, and a microtubule assembly assay shows that it has a reduced capacity to promote microtubule assembly compared with full length tau. PMID- 8003008 TI - Cloning and sequence analysis of the gene encoding pyruvate kinase in Trypanoplasma borelli. AB - The gene coding for pyruvate kinase in Trypanoplasma borelli has been cloned and characterized. A single gene copy was found with an open reading frame for a polypeptide of 496 amino acids and a molecular mass of 54337. The deduced amino acid sequence has a calculated net charge of -3. Comparison of the sequence with those of pyruvate kinases from members of the family Trypanosomatidae revealed amino acid identities of 58.4-61.5%, and, to some extent, conservation of residues supposed to be involved in the binding of the allosteric effector fructose 2,6-bisphosphate. Some kinetic properties of Trypanoplasma borelli pyruvate kinase have been determined and appear to be similar to those of the enzyme from Trypanosoma brucei and Leishmania mexicana. PMID- 8003010 TI - Phosphorylation of c-Raf-1 by protein kinase A interferes with activation. AB - c-Raf-1 is a serine/threonine-specific protein kinase which is regulated by phosphorylation. A putative c-AMP dependent protein kinase PKA phosphorylation site with the consensus sequence RRXS, Ser43, and a predominant phosphorylation site of c-Raf-1, Ser259, can be phosphorylated by PKA in vitro as shown by comparison of phosphopeptide maps of recombinant wild-type c-Raf-1 and the corresponding mutants. In vivo stimulation of the PKA pathway by treatment of A431 cells with Forskolin results in increase of phosphorylation in Ser43. Forskolin reduces the upshift of c-Raf-1 induced by EGF-treatment. It inhibits the EGF-activation of the c-Raf-1 protein kinase activity tested in vitro with a peptide substrate. PMID- 8003009 TI - Phospholipase D is activated by phorbol ester but not CSF-1 in murine bone marrow derived macrophages. AB - Phospholipase D activity was measured in murine bone marrow-derived macrophages (BMM) treated with either colony stimulating factor-1 (CSF-1) or phorbol myristyl acetate (PMA) by measuring formation of phosphatidylbutanol (PtBut) in cells preloaded with n-butanol. Addition of 10(-7) M PMA for 15 min stimulated the amount of PtBut formed in growth arrested cells by 3-4 fold whereas no stimulation was observed with 5000 units mL-1 CSF-1 for 0.5, 2 or 15 min. Protein kinase C activity was determined in growth-arrested BMM by phosphorylation of Myristoylated Alanine-Rich C Kinase Substrate (MARCKS). PMA stimulation for 5 min increased protein kinase C activity 5-6 fold whereas CSF-1 treatment for 5 min or 15 min did not. Contrary to earlier reports, CSF-1 did not stimulate diradyl glycerol formation in BMM. These results show that stimulation of protein kinase C and the activation of phospholipase D are not involved in the early events of CSF-1-stimulated signal transduction pathways in BMM. PMID- 8003011 TI - The nitric oxide-scavenging properties of Ginkgo biloba extract EGb 761. AB - Ginkgo biloba extract EGb 761 was found to be a scavenger of nitric oxide in in vitro acellular systems, under physiological conditions. EGb 761 competed with oxyhemoglobin for reaction with nitric oxide generated during the interaction of hydroxylamine with Complex I of catalase. An EGb 761 dose-dependent decrease in the amount of nitrite formed in the reaction of oxygen with nitric oxide produced from solution of 5 mM sodium nitroprusside was also observed. These data implicate it as a potential therapeutic agent in conditions of altered production of nitric oxide. PMID- 8003012 TI - Interferon-gamma induces resistance in primary monocytes against human immunodeficiency virus type-1 infection. AB - Treatment of monocytes with interferon-gamma 1 day before, or at the time of infection with human immunodeficiency virus type-1 (HIV-1) induced complete resistance in monocytes against HIV-1 infection. There was no evidence of viral RNA, proviral DNA, p24 antigen, or reverse transcriptase activity through 2 weeks after inoculation. Ultrastructural examination of these cells showed no detectable virus particles. When interferon-gamma was added to monocytes 1 to 3 days post-infection, virus integration occurred, but the viral expression was either ablated (1 day post-infection) or significantly inhibited (3 days post infection). Treatment of monocytes with interferon-gamma before or after infection with HIV-1 produced significantly higher levels of tumor necrosis factor-alpha and interleukin-8 than untreated or uninfected monocytes. These results suggest that altered regulation of cytokines may mediate antiviral activity of interferon-gamma in monocytes. PMID- 8003013 TI - The yeast plasma membrane uracil permease is stabilized against stress induced degradation by a point mutation in a cyclin-like "destruction box". AB - Yeast uracil permease appears to be fairly stable in exponentially growing cells, but it undergoes rapid endocytosis followed by degradation when cells are submitted to adverse conditions, such as nutrient starvation or inhibition of protein synthesis. Uracil permease has a sequence (RIALGSLTD) that is very similar to the "destruction box" of mitotic cyclins. This box is required for the ubiquitin-dependent proteolysis of cyclins. We replaced the invariant arginine residue of the putative "destruction box" in uracil permease by an alanine. The mutation significantly protected the permease against stress-induced degradation. This result suggests that ligation to ubiquitin could be a signal for uracil permease degradation. PMID- 8003014 TI - A calcium-activated potassium channel in growth plate chondrocytes: regulation by protein kinase A. AB - Single channel K+ currents were recorded from inside-out patches of membrane obtained from cultured chicken growth plate chondrocytes. With a symmetrical 140 mM concentration of K+ across the cell membrane, a large conductance (211 pS), outward-rectifying, K+ channel was identified. Opening of this channel was dependent on the presence of internal Ca2+ with half maximal activation of the channel occurring with 3 microM Ca2+. The channel was blocked by internal application of tetraethylammonium (IC50 = 45 mM) and 1 mM Ba2+. Application of the catalytic subunit of protein kinase A to the cytosolic membrane resulted in over a three-fold increase in the open probability for the channel. Thus, growth plate chondrocytes contain a large-conductance, Ca(2+)-activated K+ channel which can be up-regulated during stimulation of protein kinase A. PMID- 8003015 TI - Ligand blot identification of a Manduca sexta midgut binding protein specific to three Bacillus thuringiensis CryIA-type ICPs. AB - The CryIA(a), CryIA(b) and CryIA(c) Bacillus thuringiensis insecticidal crystal proteins (ICPs) were used in ligand-blot experiments to detect specific binding proteins in brush-border membrane vesicles (BBMV) of Manduca sexta. We identified a protein which binds these three CryIA-type ICPs. The apparent molecular mass of the protein, estimated on SDS-PAGE, was 210 kDa as was the CryIA(b) binding protein previously described by Vadlamudi and col. We have also demonstrated, in ligand blot experiments, that CryIA(a) and CryIA(c) compete with CryIA(b) for binding this 210 kDa protein. Properties of the binding molecule can be correlated with knowledge previously acquired through radiolabelled binding experiments. PMID- 8003016 TI - Intracellular proteolysis and limited diversity of the Bacillus thuringiensis CryIA family of the insecticidal crystal proteins. AB - The current concept of how the highly homologous Bacillus thuringiensis insecticidal crystal protein genes (cry genes) evolved is through recombination among themselves. The cryIA gene family, which is more than 80% identical, consists of only three known genes, even through they are often found together in the same bacterium. To examine the lack of diversity among these genes, recombinatorial chimeric protein toxin genes were constructed and transformed into E. coli, B. subtilis, and B. thuringiensis. Of the nine chimeric proteins examined in this work; three were degraded in E. coli, five in B. subtilis, and seven in B. thuringiensis, suggesting that most Cry proteins resulting from recombination events are degraded by intracellular proteases that are particularly prevalent in B. thuringiensis. PMID- 8003017 TI - Autoproteolytic activation of the mouse prohormone convertase mPC1. AB - In this study the activation of the prohormone convertase mPC1 was determined. Expression and characterization of catalytic domain mutations (Ser382 to Ala or His208 to Ala) in the prohormone convertase mPC1, unequivocally demonstrated that pro-region cleavage proceeds by an autocatalytic mechanism. Furthermore, these results suggest that autoproteolysis may be the result of an intramolecular reaction, since proregion processing of the active-site mutant could not be complemented by the overexpression of active furin or PC1. Additionally coexpression of a cleavage-site mutant (Arg110-Ala) with the substrate prorelaxin further demonstrated that autoproteolysis is required for the full activity of PC1. PMID- 8003019 TI - Intrinsic fluorescence of E. coli RNA polymerase as a probe for its conformational changes during transcription initiation. AB - A simple fluorimetric assay based on internal fluorescence of tryptophan residues of E. Coli RNA polymerase has been developed to ascertain the number of steps during conversion of closed complex of the polymerase-promoter (trp promoter cloned in plasmid pDR720) to open complex. Our results from measurement on relative ratio of fluorescence at 340 nm (lambda ex = 295 nm) for free and promoter-bound RNA polymerase as a function of temperature, within the range 4 degrees C to 37 degrees C, indicate following equilibria for the above conversion: R+P<-->RPc<-->RPi1<-->RPi2<-->RPo. Apart from detection of one more intermediate in terms of conformational states of the bound RNA polymerase, second feature of our studies is the examination of conformational state of the polymerase using accessibility of fluorophor, tryptophan residues, to a neutral quencher, acrylamide, as the probe. We observe that in terms of accessibility of tryptophan residues in protein, intermediate complex, RPi2, is conformationally most perturbed in comparison to free polymerase. Implications of these results are discussed and compared with the available reports from footprinting and gel retardation assays of RNA polymerase-promoter interactions. PMID- 8003018 TI - IGF-I induces the uncoupling protein gene expression in fetal rat brown adipocyte primary cultures: role of C/EBP transcription factors. AB - Fetal rat brown adipocytes proliferate and reach confluence when cultured in the presence of serum, almost losing their expression of the tissue-specific gene uncoupling protein (UCP). Confluent cells in a serum-free medium induced the expression of UCP in response to 1.4 nM IGF-I at 72 h, in a time-dependent manner. This effect was not produced by 1 nM insulin. However, insulin but not IGF-I induced the expression of the lipogenic marker malic enzyme, suggesting that IGF-I but not insulin is involved in the thermogenic differentiation process of fetal brown adipocytes. Furthermore, the expression of C/EBP transcription factors was present in fetal brown adipocytes prior culture, decreasing during cell proliferation throughout culture. After confluence, insulin induced the expression of C/EBP alpha and delta, whereas the expression of C/EBP beta remained essentially unmodified. IGF-I induced C/EBP alpha but decreased C/EBP delta, this might indicate that both transcription factors play a reciprocal role in the expression of the tissue specific UCP gene. PMID- 8003020 TI - Fluorogenic peptides containing only alpha-amino acids. AB - Fluorogenic substrates for endopeptidases are often prepared by attaching fluorophores and quenchers to opposite ends of the peptide substrates. Here, we describe a new approach by incorporating tryptophan and p-nitrophenylalanine into peptides to give fluorogenic substrates composed entirely of alpha-amino acids. Two advantages are apparent: (1) They can be prepared on a peptide synthesizer; no synthetic expertise is required. (2) Both ends of these peptides are free; other residues can be attached to increase their solubilities or to label them with affinity ligands. We tested the applicability of this new approach by developing a continuous assay for renin, a protease with unusually stringent substrate specificity. The fact that new fluorogenic peptides exhibited similar kinetic properties as those of known renin substrates suggests that this new method should be generally applicable to other proteases. PMID- 8003021 TI - Sequence analysis of the third dnaK homolog gene in Synechococcus sp. PCC7942. AB - The nucleotide sequence of the third dnaK homolog gene from Synechococcus sp. PCC7942 has been determined. Deduced amino acid sequences of dnaK3 and of previously reported dnaK1 and dnaK2 were compared with Hsp70s from various species. Among the three DnaK homologs, DnaK2 shows close relationship to chloroplast proteins and DnaK3 also has some similarities to them. On the other hand, DnaK1 has few chloroplast-specific motifs and forms a deep branch of the prokaryotic cluster in the phylogenetic tree. PMID- 8003022 TI - Signalling via MHC class II molecules selectively induces IL-1 beta over IL-1 receptor antagonist gene expression. AB - Activation of human monocytes or human monocytic cell lines by several types of stimuli coordinately induces IL-1 beta and its antagonist (IL-1Ra) gene expression; alterations in their balance seem to mediate the inflammatory response. Using the human monocytic cell line THP-1, we report that superantigens, such as staphylococcal enterotoxin A (SEA) and Mycoplasma arthritidis -derived superantigen (MAM) induce an increase in the level of IL-1 beta mRNA without any detectable effect on IL-Ra mRNA. Unlike MAM-induced IL-1 beta mRNA, SEA-induced IL-1 beta mRNA was adequately translated into protein. Superantigen-induced gene expression is mediated by signalling, via their receptors, the MHC class II molecules. Thus, it appears that this mode of signalling selectively induces the proinflammatory cytokine IL-1 beta gene expression which, by itself, can have major importance in disease pathology especially in autoimmune diseases. PMID- 8003023 TI - Human and rat osteoblast-like cells express stathmin, a growth-regulatory protein. AB - We used the differential display polymerase chain reaction method of Liang and Pardee (Science (1992) 257:967-971) to identify a growth-regulatory protein, stathmin or oncoprotein 18, in human and rat osteoblast-like cells. When messenger ribonuleic acid from human osteosarcoma (Saos-2) cells treated with 10( 8)M 1,25-dihydroxyvitamin D3 was compared with that of cells treated with vehicle alone by this method, we observed an increase in the intensity of a band that on subsequent DNA sequence analysis was found to encode stathmin. We examined normal human osteoblast-like cells, transformed human osteoblast-like cells (HOBIT), human osteosarcoma cells (Saos-2), and rat osteoblast cell (ROS 17/2.8, ROS 25/1) lines for the presence of the messenger RNA for stathmin. All osteoblast-like cells examined expressed the RNA for this protein. Western analysis of the protein of these cells with a polyclonal antibody directed against stathmin showed the presence of a M(r) 19,000 band. We conclude that human and rat osteoblast-like cells express stathmin and that this protein could play a role in regulation of the growth of these cells in response to various hormonal stimuli. PMID- 8003024 TI - Site directed substitutions suggest that His-418 of beta-galactosidase (E. coli) is a ligand to Mg2+. AB - Site directed mutagenesis was used to replace His-418 of beta-galactosidase with Phe (H418F) or Glu (H418E). Kinetic analysis revealed that H418F beta galactosidase was not significantly affected by the presence of Mg2+ whereas H418E beta-galactosidase retained its sensitivity to Mg2+. H418F had a kcat similar to that of Mg(2+)-free wild type beta-galactosidase. Its pH profile was shifted 1.0 pH unit lower on the alkaline side as compared to wild type beta galactosidase (with Mg2+). This was similar to the shifting of the wild type beta galactosidase pH profile when Mg2+ was absent. H418E beta-galactosidase was inactivated (rather than activated) by Mg2+ binding. Equilibrium dialysis studies indicated that H418E and wild type beta-galactosidase bind Mg2+ tightly whereas H418F does not. The results indicate that His-418 is probably a ligand to Mg2+. PMID- 8003025 TI - Role of zinc-coordination and of the glutathione redox couple in the redox susceptibility of human transcription factor Sp1. AB - We show that thiol-groups confer redox-susceptibility to the zinc-finger transcription factor Sp1 and that this redox-susceptibility is prevented by DNA binding and depends on zinc-coordination of the protein. Apo-Sp1 contained in metal depleted nuclear extracts of human K562 cells exhibited a markedly increased susceptibility towards oxidizing and alkylating agents, as compared to holo-Sp 1. Moreover, DNA binding of apo-Sp1, but not of the holo-protein, was dramatically decreased in the presence of GSH/GSSG ratios within the physiological range. We compared these results with the redox behaviour of two other transcription factors, OTF-1 and NF1, which was found to be different in several aspects from that of Sp1. PMID- 8003026 TI - A stable leukocyte-derived factor inhibits platelet aggregation. AB - The effect of human polymorphonuclear leukocyte (PMN)-derived supernatants on platelet aggregation was studied. The results showed that the supernatants produced a concentration-dependent inhibition of the platelet aggregation in response to thrombin. The effect was mainly on the second phase of the aggregation, suggesting that the secretory mechanisms of the platelets are disturbed. The activity of the supernatants was not reduced after treatment with heat (95 degrees C for 30 minutes), extreme pH (pH 12 or pH 2) or protease. In conclusion, human PMNs release a stable non-protein factor that inhibits platelet aggregation. PMID- 8003027 TI - Nitric oxide is present in exhaled breath in humans: direct GC-MS confirmation. AB - The physiological role of nitric oxide (NO) is being investigated in many experimental and clinical settings. There is considerable evidence that NO is involved in the regulation of lung vascular function. In addition there are many studies reporting the beneficial effect of NO inhalation. NO formed from L Arginine has been detected in exhaled breath using indirect mass spectrometry and chemiluminescence. Both methods provided good evidence for the presence of NO in breath samples but were not unequivocal. We therefore developed a method using gas-chromatography-mass spectrometry which allowed us to measure trace levels of NO in air and breath. Eight healthy volunteers supplied numerous breath samples for analysis. A clear peak for nitric oxide was observed in seven volunteers. The mean level was 13ppb (n = 7, range < 2 to 19ppb). This data is in good agreement with our previous data and unequivocally confirms the presence of nitric oxide in human breath. PMID- 8003028 TI - Delivery of plasmid DNA to glial cells using pH-sensitive immunoliposomes. AB - Immunoliposomes were constructed with an antibody specific to glial cells. They were used to examine the specificity and efficacy of cell type plasmid transfection. Liposomes contained a beta-galactosidase gene under control of an SV-40 promotor. Two different monoclonal antibodies of a different subclass, IgM and IgG, were examined for their targeting ability using immunoliposomes. Cultured C6 glioma (specific target cell type) and NIH 3T3 (control cell type, fibroblast) cells were transfected using these immunoliposomes. Results indicate a three-fold increase in transfection by the glial specific immunoliposomes, "gliasomes", in glial cell culture over control liposomes. Gliasomes were exposed to NIH 3T3 cells and showed no enhanced transfection over control liposomes. Gliasomes were tested for their specificity by the addition of excess antibody to the cell culture in order to saturate specific receptors on C6 glioma cells. Results indicate a reduced transfection, nearly three-fold, in cells that were saturated with excess antibody prior to exposure to the immunoliposomes. PMID- 8003029 TI - Molecular cloning of the human histamine H1 receptor gene. AB - The human histamine H1 receptor gene, an intron-lacking gene, was isolated with bovine H1 receptor cDNA [Yamashita, M., Fukui, H., Sugama, K., Horio, Y., Ito, S., Mizuguchi, H., and Wada, H. (1991) Proc. Natl. Acad. Sci. USA 88, 11515 11519] used as a probe. The receptor protein deduced from the nucleotide sequence of this gene was composed of 487 amino acid residues with a calculated Mr of 55,781 and possessed characteristic properties of GTP binding protein-coupled receptors. At the 5' flanking region of the human H1 receptor gene, we located potential TATA box and CACCC sequences, AP1 binding site-like sequences, glucocorticoid responsive element-like sequences, and other binding sequences for inducers. Northern blot analysis showed that H1 receptor mRNAs visualized as two bands with 3.0-kilobase and 3.5-kilobase nucleotides were expressed in peripheral tissues such as placenta, lung, skeletal muscle, and kidney and that only one species with 3.5-kilobase nucleotides was present in the brain. H1 receptor mRNA was most abundant in the placenta. The human H1 receptor gene was mapped to the chromosome 3p25 by the fluorescence in situ hybridization method. PMID- 8003030 TI - Epidermal growth factor counteracts insulin-induced expression of glucokinase in hepatocytes. AB - Hepatic glucokinase is induced by insulin and repressed by glucagon. The effects of epidermal growth factor (EGF) on glucokinase expression were investigated in rat hepatocytes. EGF does not affect the decline in glucokinase activity in hepatocytes cultured for 48h in the absence of insulin, but it counteracts the increase in activity induced by insulin. This effect of EGF is greater in cells cultured at low cell density than in confluent cultures. EGF suppressed the insulin-induced increase in glucokinase mRNA levels by 50% indicating that its effect is at least in part at a pretranslational level. However, it potentiated the stimulatory effect of insulin on glucose-6-phosphate dehydrogenase activity and mRNA, indicating that the effect on glucokinase expression is due to a specific post-receptor mechanism. The effect of EGF on glucokinase mRNA expression is mimicked by phospholipase D but not by phosphatidylinositol specific phospholipase C or by phorbol ester, an activator of protein kinase C, suggesting that it is unlikely to be mediated by activation of protein kinase C. PMID- 8003031 TI - Zinc content of promatrilysin, matrilysin and the stromelysin catalytic domain. AB - Promatrilysin expressed in Escherichia coli and Chinese hamster ovary cells contains 2.36 +/- 0.19 and 2.13 +/- 0.39 moles of zinc per mole of protein, respectively, while the activated enzyme contains 2.22 +/- 0.21. The catalytic domain of stromelysin-1 expressed in E. coli contains 2.22 +/- 0.11. Thus these matrix metalloproteinases contain two metal binding sites at which zinc is bound firmly and possibly a third site at which it is bound weakly. Promatrilysin and matrilysin do not contain significant amounts of Fe, Cu, Mn, or Ni. All known matrix metalloproteinases have a sequence homologous to the zinc binding site of astacin, HExxHxxGxxH, suggesting that one of the zinc sites is catalytic in agreement with the known inhibition of these enzymes by chelators. PMID- 8003033 TI - Changes in carnitine palmitoyltransferase-I mRNA abundance produced by hyperthyroidism and hypothyroidism parallel changes in activity. AB - To study the regulation of carnitine palmitoyltransferase-I by thyroid hormone, a cDNA was obtained by PCR amplification of DNA obtained by reverse transcription of rat liver RNA. CPT-I mRNA abundance was measured in livers of hyperthyroid, euthyroid and hypothyroid rats. In hypothyroid rats, the CPT-I mRNA levels decreased 40-fold relative to that of the hyperthyroid animals. These changes paralleled alterations in enzyme activity. These data suggest that CPT-I is regulated at the transcriptional level by thyroid hormone. PMID- 8003032 TI - Cytokines induce nitric oxide production in mouse osteoblasts. AB - MC3T3-E1 mouse clonal osteogenic cells were incubated with interferon-gamma, interleukin-1 beta, tumor necrosis factor-alpha, and E. coli lipopolysaccharide. TNF alpha, IL-1 beta, and LPS caused a dose- and time-dependent increase of nitrite (NO2-), the stable metabolite of nitric oxide (NO), in conditioned media over 48 hours, while IFN gamma had a minimal effect. Different combinations of the same factors caused a synergistic enhancement of NO2- accumulation, except for IL-1 beta with LPS. The earliest detectable NO2- production was at 6-9 hours, with continued accumulation over 48 hours. NO2- production was inhibited dose dependently by three arginine analogs known to be specific inhibitors of NO synthase, as well as by actinomycin D, cycloheximide, and dexamethasone; EGTA or indomethacin had a small inhibitory effect. It is concluded that osteoblast-like cells can be induced by proinflammatory cytokines and bacterial endotoxin to produce NO, which can play an important role in bone pathophysiology. PMID- 8003034 TI - Cloning and expression of the gene encoding the 7Fe type ferredoxin from a thermophilic hydrogen oxidizing bacterium, Bacillus schlegelii. AB - The structural gene (fdxA) coding for a 7Fe type ferredoxin of a thermophilic hydrogen oxidizing bacterium Bacillus schlegelii has been cloned and sequenced. The fdxA coding region is 231 nucleotides which codes for a 77 amino acids protein with the molecular weight of 8,744 except for iron-sulfur clusters. The fdxA gene has been expressed in E. coli to obtain the recombinant ferredoxin. The recombinant ferredoxin have shown the identical properties to the native one for absorption spectra, and SDS-PAGE. PMID- 8003035 TI - Gene targeting constructs: effects of vector topology on co-expression efficiency of positive and negative selectable marker genes. AB - Targeting of DNA into specific chromosomal loci often involves the use of a negative selectable marker gene to enrich for cell clones that have undergone homologous recombination. In this study we asked if the arrangement of the positive and negative markers in 'knockout' constructs can influence the expression of a lacZ gene that was used as a negative marker. We show that constructs which differ only in their topology have vastly different co expression efficiencies. The site of DNA linearization was critical. While linearizing at the 5'-end of the lacZ gene was compatible with efficient lacZ expression, linearizing at the 3'-end was always detrimental. We also demonstrate that the topology of the template was more important than the promoter used to drive lacZ expression. PMID- 8003036 TI - Stimulation of transcription factors NF kappa B and AP1 in endothelial cells subjected to shear stress. AB - Hemodynamic shear stress forces influence several important endothelial genes associated with arterial relaxation, pro/anti-coagulation, and growth control; however, the regulatory pathways remain unclear. Here we demonstrate stimulation of DNA binding activities of nuclear factor kappa B (NF kappa B), a member of the Rel Family of transcription factors, and nuclear factor activator protein-1 (AP 1) following exposure of endothelial cells to unidirectional shear stress in laminar flow. NF kappa B binding was stimulated within 30 minutes, reaching and maintaining maximal levels at 1 hour. DNA binding activity was inhibited by pre incubation of nuclear extract with antibody directed against NF kappa B p65 subunit. AP-1 binding activity was biphasic, rising fourfold within 20 minutes and returning to basal levels before steadily increasing by 2 hours to a high level relative to basal values. These protein kinase C-coupled transcriptional factors may modulate endothelial genes that are shear stress-responsive and that possess appropriate binding sites in the promoter region. PMID- 8003037 TI - Proline-protein interactions: protection of structural and functional integrity of M4 lactate dehydrogenase. AB - A well defined labile isozyme, rabbit muscle M4-lactate dehydrogenase was denatured under freeze-thaw, heat and GuHCl treatment in the presence and absence of proline, and the corresponding structural changes of the enzyme were monitored through fluorescence and CD spectral studies. The data reveal that proline confers protection to the structural integrity of the enzyme, thereby protecting its activity. This was attributed to its property of forming hydrophilic colloids in aqueous media with a hydrophobic backbone interacting with protein. Unlike other osmolytes, proline is proposed to act on the enzyme stability not only by inducing preferential hydration of proteins but also through the interactions of its multimeric hydrophobic backbone with the solvent-accessible hydrophobic regions of the enzyme. PMID- 8003039 TI - Induction of the cytochrome P450 3A subfamily in rat liver correlates with the binding of inducers to a microsomal protein. AB - The specific binding of the archetypal cytochrome P450 3A subfamily (CYP3A) inducer dexamethasone is examined in microsomal fractions since rat and human liver CYP3A is induced by glucocorticoids through a mechanism which is apparently independent of the cytosolic glucocorticoid receptor. Dexamethasone binds in a specific and saturable manner to microsomes with an affinity constant (Kd) of 59 +/- 12.9 nM which compares to a Kd of 2.3 +/- 0.17 nM in cytosol. The total receptor concentrations ([LR]emax) in microsomes and cytosol are 9.5 +/- 1.67 pmols/mg protein and 410 +/- 167 fmol/mg protein respectively. The microsomal binding of dexamethasone is antagonised by several transcriptional and/or post transcriptional CYP3A inducers with decreasing potency pregnenolone 16 alpha carbonitrile > metyrapone > phenobarbitone. Troleandomycin, which indirectly induces CYP3A1 in vivo and by protein stabilisation, does not antagonise the binding of dexamethasone in microsomes. The transcriptional and/or post transcriptional induction of CYP3A may therefore be associated with the interaction of inducers with a microsomal protein. PMID- 8003038 TI - Developmental expression of the glucose-dependent insulinotropic polypeptide gene in rat intestine. AB - The developmental expression of the glucose-dependent insulinotropic polypeptide (GIP) gene was investigated in rat intestine. Steady state levels of GIP mRNA were determined in the intestine during fetal and postnatal development by double ribonuclease protection assays. GIP mRNA could be detected as early as day 20 of embryonic development and very low levels remained until postnatal day 3. The GIP mRNA levels increased markedly in the period between days 3 and 5 of postnatal life and then gradually increased toward adult levels. Since intron 1 of the GIP gene contains putative TATA and CCAAT boxes, and some potential cis-acting promoter elements, we examined whether or not another transcript starting from exon 2 of the GIP gene is expressed during development of rat intestine. Ribonuclease protection assays suggested that although an abbreviated transcript might exist starting from exon 2, it appears to be minor and its relative abundance is unchanged during development or following intraduodenal glucose stimulation. These observations suggest that GIP may play an important role in early postnatal development probably associated with suckling. PMID- 8003040 TI - Inhibition of Sendai virus hemagglutinin neuraminidase by the fusion protein. AB - The Sendai virus envelope contains two glycoproteins: the fusion (F) protein and the hemagglutinin-neuraminidase (HN). Inactivation of F causes the loss of fusogenic activity and an increase of the neuraminidase activity of HN. After inactivation of F, HN can be inhibited by fetuin or asialofetuin, as already observed on the water-soluble, C-terminal fragment of HN (Dallocchio, F., Bellini, T., Martuscelli, G., Baiocchi, M., & Tomasi, M. (1991) Biochem. Int. 25, 663-668). Disruption of viral envelopes by detergents does not affect the neuraminidase activity of virions containing inactive F, while it causes an increase of the neuraminidase activity in native virions. Reconstitution of HN into liposomes is accompanied by a decrease of enzymatic activity, due to the random inside-outside distribution of the protein. However, the decrease of the neuraminidase activity is higher in liposomes containing both HN and F. These data suggest that F inhibits the neuraminidase activity of HN. PMID- 8003042 TI - [Primary structure of an intracellular serine proteinase from Bacillus amyloliquefaciens. II. Amino acid sequence of peptides in a chymotrypsin hydrolysate]. AB - Chymotrypsin hydrolyzate of the intracellular serine protease was separated by ion-exchange chromatography on a sulphocationite resin followed by HPLC to yield fifty one individual peptides. Their sequences, corresponding in total to 381 amino acid residues, were determined by the manual Edman procedure. PMID- 8003041 TI - Molecular cloning and characterization of murine cyclin E. AB - Using a monoclonal antibody developed to a mouse trophectodermal carcinoma stem cell line E6496D lysate, we have identified the gene that encodes murine cyclin E. The cDNA contains a consensus cyclin box and a long 3' untranslated region and shares over 75% homology with human cyclin E cDNA. We show that the gene is expressed in fetal tissues, embryonal carcinoma F9 cells and yolk sac carcinoma PYS-2 cells, but is not expressed in preimplantation stages of development. In adult tissues, cycE mRNA is detectable in the spleen and to a lesser extent in the testis and brain. These data show that cycE is developmentally regulated and unevenly expressed in fetal and adult mouse tissues. PMID- 8003043 TI - [Synthesis of new fragments of VP1 protein fragments from foot and mouth disease virus type A22. Synthesis of fragments 134-139, 134-145, 140-145, 150-155, and 150-159]. AB - Fragments 134-145 and 150-159 of the antigenic-region of the VP1 protein of the A22 foot-and-mouth disease virus were synthesized by classic methods of peptide chemistry with isobutyl chloroformate as a coupling reagent. After purification by HPLG and amino acid analysis, the free peptides H-Gly-Lys-Tyr-Ser-Ala-Gly-Gly Leu-Gly-Arg-Arg-Gly-OH and H-Leu-Ala-Ala-Arg-Val-Ala-Lys-Gln-Leu-Pro-OH were conjugated with BSA by means of N,N-dicyclohexylcarbodiimide. The conjugates were used, with complete Freund adjuvant, for immunization on guinea pigs. The antibodies formed had a virus neutralization activity. PMID- 8003044 TI - [A new fluorogenic substrate of carboxypeptidase H--o-coumaroylphenylalanyl alanyl-arginine]. AB - New fluorogenic substrate of carboxypeptidase H, Cum-Phe-Ala-Arg-OH, is hydrolyzed by this enzyme to give Cum-Phe-Ala-OH, which is completely extracted by chloroform from the reaction mixture and whose fluorescence increases remarkably by the presence of triethylamine. When the hydrolysis of the novel substrate is compared with Dns-Phe-Ala-Arg-OH, the former has Km twice as low (30 microM) and kcat four times as high (5.8 s-1). Activation of the enzyme by Co2+ in reactions with the two substrates was also studied. The novel substrate is useful for the enzyme's assay in homogenates of various animal tissues. PMID- 8003045 TI - [Affinity modification of EcoRII restriction endonuclease by a DNA-duplex containing a monosubstituted pyrophosphate internucleotide bond]. AB - Oligonucleotide duplex with an active monosubstituted pyrophosphate bond within the recognition site of the EcoRII restriction endonuclease was cross-linked to this enzyme with a yield of 10-15%. The cross-linking specificity was proved by the absence of the cross-linking to a DNA duplex with the same modification but without the EcoRII recognition site as well as by unmodified EcoRII substrate's inhibition of the cross-linking. PMID- 8003046 TI - [Design of mixed polymers based on DNA fragments with consensus promotor elements, separated by nonnucleotide segments]. AB - Mixed oligomers, representing oligonucleotides connected with long non-nucleotide spacers, have been synthesized using phosphoramidite chemistry. The oligonucleotide moieties of the mixed oligomers fully or partially correspond in the structure to the consensus elements of -35 (TTGACA) and -10 (TATAATG) regions of prokaryotic promoters. The non-nucleotide spacers, approximating in size 17 membered DNA fragments, were synthesized using phosphoramidite derivatives of polyethylene glycol (PEG600), tetraethylene glycol or dodecanediol. It is shown that the oligonucleotide moieties of the mixed oligomers can form "normal" DNA like antiparallel complementary complexes, being the substrates of T4 DNA ligase. To obtain the DNA-like polymers with alternating natural and non-natural regions or cyclic structures, the enzymatic ligation of different complexes of the oligomers synthesized was studied. PMID- 8003047 TI - [Synthesis of lipophilic muramoyldipeptide derivatives]. AB - beta-Glycosides of N-acetylglucosamine, obtained by the oxazoline synthesis, with 2-dodecyltetradecanol-1 and 2,3-didodecyloxypropanol-1 as aglycons, were converted into muramic acids and then coupled with the dipeptide to give lipophilic glycosides of muramoyldipeptide. On the other hand, condensation of 2 dodecyltetradecanyl esters of glycine and 6-aminohexanoic acid with Boc-L-Ala-D Glu-NH2 gave the corresponding lipophilic tripeptides, which upon coupling with alpha-benzyl-4,6-O-benzylyden-N-acetylmuramic acid yielded lipophilic esters of muramoyltripeptides. The protecting groups were removed by acid hydrolysis and hydrogenolysis. PMID- 8003048 TI - Pannus and pannocytes. Alternative models of joint destruction in rheumatoid arthritis. PMID- 8003049 TI - Searching for the cause of fibromyalgia: is there a defect in energy metabolism? PMID- 8003050 TI - Lack of association between fibromyalgia syndrome and abnormalities in muscle energy metabolism. AB - OBJECTIVE: To compare parameters of muscle energy metabolism in patients with fibromyalgia syndrome (FMS) and sedentary controls. METHODS: Thirteen female FMS patients and 13 female sedentary controls underwent a standardized clinical assessment (including dolorimeter measurements of the upper trapezius and tibialis anterior muscles) and a standardized aerobic fitness test including measurement of maximum oxygen uptake (VO2max). Phosphorus (31P) magnetic resonance spectroscopy studies of the upper trapezius and tibialis anterior muscles were then performed in FMS patients and controls, at rest and during and following a muscle-fatiguing exercise protocol. RESULTS: FMS patients and controls had similar levels of VO2max and of maximum voluntary contraction (MVC) of the upper trapezius and tibialis anterior muscles. After controlling for VO2max and MVC, measurements of phosphocreatine (PCr), inorganic phosphate (P(i)), and intracellular pH in these muscles were not significantly different in FMS patients versus sedentary controls either at rest, during exercise, or during recovery. In the patients with FMS, no correlation was found between overall or local pain severity and the principal muscle metabolic parameter, PCr/P(i). Inverse correlations between dolorimeter scores at 2 muscle sites and tibialis anterior PCr/P(i) were found both in patients and in controls. CONCLUSION: This study demonstrates that under the conditions studied, muscle energy metabolism in FMS is no different than that in sedentary controls. These findings do not support the hypothesis that detectable defects in muscle energy metabolism occur in FMS. PMID- 8003051 TI - Increased incidence of a resonance in the phosphodiester region of 31P nuclear magnetic resonance spectra in the skeletal muscle of fibromyalgia patients. AB - OBJECTIVE: To determine if patients with fibromyalgia syndrome (FMS) are more susceptible to activity-induced muscle damage than are healthy subjects. METHODS: Eleven FMS patients and 10 healthy subjects performed concentric and eccentric exercise with their dominant and nondominant forearms, respectively. 31P magnetic resonance spectroscopy (to assess inorganic phosphate [P(i)] and phosphocreatine [PCr]) and dolorimetry (to assess pain) were performed before and 20 minutes after exercise and at 4 subsequent 24-hour intervals. RESULTS: Neither group exhibited increased P(i)/PCr ratios or reduced dolorimetry scores following the exercise protocols. FMS patients did display a phosphodiester resonance at a higher rate than healthy subjects (37% versus 12%), but this was not related to the exercise. CONCLUSION: Unchanged P(i)/PCr ratios and dolorimetry scores following acute exercise provide evidence against the hypothesis that FMS patients are more susceptible to activity-induced muscle damage than are healthy subjects, although P(i)/Pcr and pain may not adequately document such damage. The frequent occurrence of phosphodiester in the spectra of FMS patients may indicate a sarcolemmal abnormality in these subjects. PMID- 8003052 TI - Breast-feeding and the onset of rheumatoid arthritis. AB - OBJECTIVE: In a recent study we demonstrated that the postpartum period, particularly after the first pregnancy, is a time of increased risk for the development of rheumatoid arthritis (RA). The present study was undertaken to investigate whether this risk might be explained by breast-feeding. METHODS: Through a nationwide media campaign, we identified 187 women who had developed RA within 12 months of a pregnancy, and we compared their breast-feeding histories with those of 149 similarly aged women chosen from the patient registers of a nationwide group of general practitioners. RESULTS: In all, 88 of the women with RA developed the disease after their first pregnancy. Eighty-one percent of these 88 women had breast-fed. This was higher than the breast-feeding prevalence of 50% in the 129 controls whose first pregnancy had resulted in a live birth (adjusted odds ratio [OR] 5.4, 95% confidence interval 2.5-11.4). There was a smaller increased risk of breast-feeding after a second pregnancy in the RA cases (OR 2.0) and no increase after a third pregnancy (OR 0.6). The increase in risk was greatest in those cases whose disease was erosive and who were rheumatoid factor positive. CONCLUSION: In a small group of susceptible women, exposure to breast-feeding after the first pregnancy is associated with a significant increase in risk for RA development. We postulate that this may reflect hormonal influences, specifically the high level of the proinflammatory hormone prolactin. PMID- 8003053 TI - The lag time between onset of symptoms and diagnosis of rheumatoid arthritis. AB - OBJECTIVE: Rheumatoid arthritis (RA) may be biologically reversible if treated in the first several months, yet it is unknown whether patients are diagnosed that early. We investigated the lag time between symptom onset and diagnosis of RA in a population with excellent access to rheumatology care. METHODS: Using review of medical records, we evaluated all patients newly diagnosed as having RA from 1987 through 1990, at a health maintenance organization in central Massachusetts. Total lag time from symptom onset to first definite diagnosis was divided into medical encounter lag time (from symptom onset to first medical encounter) and diagnosis lag time (from first medical encounter to diagnosis). RESULTS: The median total lag time was 36 weeks (range 4 weeks to > 10 years). The median medical encounter lag time was 4 weeks (not all patients included in the analysis). The median diagnosis lag time was 18 weeks. Diagnosis lag time was shorter for patients with progressive disease and positive rheumatoid factor on the initial test. Of 25 patients with symmetric arthritis and positive rheumatoid factor, only 5 (20%) were diagnosed within 2 months, and 10 (40%) were diagnosed more than 6 months after symptom onset. CONCLUSION: RA diagnosis is usually delayed for several months after symptoms begin, in large part because of delay in diagnosis by the physician. Thus, the goal of initiating treatment extremely early may be unrealistic for most patients. PMID- 8003054 TI - The sensitivity and specificity of computerized databases for the diagnosis of rheumatoid arthritis. AB - OBJECTIVE: To examine the accuracy of a computerized medical database for the diagnosis of rheumatoid arthritis (RA). METHODS: The complete medical records of all prevalent cases of RA (according to the 1987 American College of Rheumatology diagnostic criteria) on January 1, 1987 were reviewed to determine the sensitivity, specificity, and predictive value of database diagnoses compared with those obtained by medical record review. Agreement between database and medical record diagnoses was calculated using the kappa statistic. RESULTS: Computerized database diagnoses of RA had a sensitivity of 89%, a specificity of 74%, a positive predictive value of 57%, and a negative predictive value of 94% compared with diagnoses based on clinical information abstracted from the complete medical record. Agreement between database and medical record diagnoses was poor (kappa = 0.54). CONCLUSION: The sole reliance on such databases for the diagnoses of RA can result in substantial misdiagnosis. PMID- 8003055 TI - Long-term effect of omega-3 fatty acid supplementation in active rheumatoid arthritis. A 12-month, double-blind, controlled study. AB - OBJECTIVE: To study the long-term effects of supplementation with omega-3 fatty acids (omega 3) in patients with active rheumatoid arthritis. METHODS: Ninety patients were enrolled in a 12-month, double-blind, randomized study comparing daily supplementations with either 2.6 gm of omega 3, or 1.3 gm of omega 3 + 3 gm of olive oil, or 6 gm of olive oil. RESULTS: Significant improvement in the patient's global evaluation and in the physician's assessment of pain was observed only in those taking 2.6 gm/day of omega 3. The proportions of patients who improved and of those who were able to reduce their concomitant antirheumatic medications were significantly greater with 2.6 gm/day of omega 3. CONCLUSION: Daily supplementation with 2.6 gm of omega 3 results in significant clinical benefit and may reduce the need for concomitant antirheumatic medication. PMID- 8003056 TI - Chloroquine reduces the bioavailability of methotrexate in patients with rheumatoid arthritis. A possible mechanism of reduced hepatotoxicity. AB - OBJECTIVE: To evaluate the effects of a single dose of chloroquine (CQ) on the pharmacokinetics of methotrexate (MTX) in patients with rheumatoid arthritis. METHODS: Eleven patients (ages 41-75 years) who were taking oral doses of MTX (15 mg/week) were studied after a dose of MTX alone and after a dose of MTX plus CQ (250 mg). Plasma and urine samples were collected for 24 hours after dose intake, and the concentrations of MTX and its major metabolite 7-hydroxymethotrexate were determined by high-performance liquid chromatography. RESULTS: Administration of CQ together with MTX caused a reduction in the area under the plasma MTX concentration versus time curve (AUC). The median value of individual AUC ratios (MTX/MTX + CQ) was 1.6 (95% confidence interval 1.2-3.6). CONCLUSION: The most likely mechanism for the interaction is that CQ reduces the bioavailability of MTX. This gives a possible explanation for a suggested reduction in MTX associated liver toxicity by coadministration of CQ. The significance of the interaction for the therapeutic effect remains to be elucidated. PMID- 8003057 TI - Differential expression of two major cytokines produced by neutrophils, interleukin-8 and the interleukin-1 receptor antagonist, in neutrophils isolated from the synovial fluid and peripheral blood of patients with rheumatoid arthritis. AB - OBJECTIVE: Neutrophils have been shown to produce interleukin-8 (IL-8) and interleukin-1 receptor antagonist (IL-1ra) in large amounts compared with other cytokines. Since IL-8 has a proinflammatory action whereas IL-1ra is antiinflammatory, our objective was to examine the relative levels of production of these cytokines by synovial fluid (SF) neutrophils isolated from patients with rheumatoid arthritis (RA). METHODS: We measured cytokine production using an enzyme-linked immunosorbent assay and analyzed messenger RNA accumulation in cells by Northern blot. RESULTS: SF neutrophils produced significantly more IL-8 and IL-1 beta, but significantly less IL-1ra, than peripheral blood neutrophils. CONCLUSION: These observations provide new information on the production of pro- and antiinflammatory molecules by neutrophils in the SF environment, and their possible role in RA. PMID- 8003058 TI - Preferential utilization of a novel V lambda 3 gene in monoclonal rheumatoid factors derived from the synovial cells of rheumatoid arthritis patients. AB - OBJECTIVE: To further our understanding about the molecular genetics of rheumatoid factor (RF) in rheumatoid arthritis (RA). METHODS: The heavy and light chain variable region (V) genes of 5 new human monoclonal IgM RFs were cloned and sequenced using the polymerase chain reaction and the dideoxynucleotide termination method. RESULTS: The results reveal the recurrent usage in two RA patients of a novel V lambda 3 germline gene, designated Humlv3c93. Specifically, in 2 of 3 RFs (C93 and D53) from one patient, the light chains in the V lambda gene-encoded region were identical to each other and to the light chain of an RF (H4) from another patient. Serologically, the light chains of these 3 RFs were classified as members of the V lambda 3b sub-subgroup. Each of the RFs was encoded by a different VH gene. Both C93 and D53 bound specifically with human and rabbit IgG, whereas H4 was monospecific for rabbit IgG. CONCLUSION: Since the lv3c93 gene is not homologous to any reported V lambda sequence from natural autoantibodies, it is possible that lv3c93 may represent a disease-specific RF related V lambda gene. Moreover, the amino acid sequence CSGGSCY in the third complementarity-determining regions of 2 of the RF heavy chains is encoded by the DLR2 gene segment and has been found previously in 2 other RA-derived RFs, and thus may play a significant role in antigen binding. PMID- 8003059 TI - Association of patterns of labial salivary gland inflammation with keratoconjunctivitis sicca. Analysis of 618 patients with suspected Sjogren's syndrome. AB - OBJECTIVE: To determine the association between patterns of inflammation in labial salivary glands (LSG) and the ocular component of Sjogren's syndrome (SS). METHODS: We classified LSG biopsy specimens from 618 patients with suspected SS as showing focal lymphocytic sialadenitis (FLS), other chronic sialadenitis (CS), or other diagnoses. We then determined the association of the other component of primary SS, keratoconjunctivitis sicca (KCS), with FLS, CS, parotid flow rate, and xerostomia. RESULTS: FLS, rather than CS, was associated with a diagnosis of KCS (chi 2 = 191, P < 0.0001). The severity of KCS correlated directly with the severity of FLS (r = 0.52, P < 0.0001), but not of CS, and correlated inversely with parotid flow rate in those patients who had FLS (r = -0.29), but not in those who had CS (r = -0.03). Xerostomia was marginally associated with KCS (chi 2 = 5, P = 0.02). CONCLUSION: The stronger KCS association found in patients whose LSG biopsies show FLS makes FLS the best criterion presently available for diagnosing the salivary component of SS. CS is a common feature of labial salivary glands but is neither associated with SS nor an end stage of primary SS. Histopathologic examination of salivary tissue is currently essential for diagnosing primary SS as well as secondary SS in which KCS is lacking, especially cases to be included in studies of SS. PMID- 8003060 TI - Treatment of Lyme arthritis. AB - OBJECTIVE: To test treatment regimens for Lyme arthritis. METHODS: Patients were randomly assigned to treatment with doxycycline or amoxicillin plus probenecid for 30 days. Patients who had persistent arthritis for at least 3 months after treatment with oral antibiotics or parenteral penicillin were given intravenous ceftriaxone for 2 weeks. RESULTS: Eighteen of the 20 patients treated with doxycycline and 16 of the 18 patients who completed the amoxicillin regimen had resolution of the arthritis within 1-3 months after study entry. However, neuroborreliosis later developed in 5 patients, 4 of whom had received the amoxicillin regimen. Of 16 patients (2 from the oral antibiotic study and 14 additional patients) who had persistent arthritis despite previous oral antibiotics or parenteral penicillin, none had resolution of the arthritis within 3 months after ceftriaxone therapy. The HLA-DR4 specificity and OspA reactivity were associated with a lack of response. CONCLUSION: Lyme arthritis can usually be treated successfully with oral antibiotics, but patients may still develop neuroborreliosis. Patients with certain genetic and immune markers may have persistent arthritis despite treatment with oral or intravenous antibiotics. PMID- 8003061 TI - Evaluation of memory, learning ability, and clinical neurologic function in pathogen-free mice with systemic lupus erythematosus. AB - OBJECTIVE: To determine if neurologic impairment is related to progressive autoimmune disease in 3 murine models of systemic lupus erythematosus (SLE): MRL/lpr, NZB, and NZB/WF1. METHODS: Sensorimotor function, learning, and memory were tested within strains at specific ages, before and after the appearance of SLE. These parameters were also compared between strains for young and older lupus mice and their congenic controls with reduced autoimmune disease (MRL/lpr versus MRL/+; NZB versus NZB/xid). RESULTS: Abnormal neurologic features were present at a much higher frequency in MRL/lpr mice than in age-matched MRL/+ control mice, and sensorimotor function deficits were also seen in NZB/WF1 mice. Strains that develop lupus showed deficits on a water-escape, distal cue discrimination task and on a food-rewarded, proximal cue discrimination task, but the cognitive impairments were not global. CONCLUSION: MRL/lpr, NZB, and NZB/WF1 mice differed in terms of which behaviors were impaired as well as when those impairments appeared. PMID- 8003062 TI - Serum levels of soluble interleukin-2 receptor. A marker of disease activity in localized scleroderma. AB - OBJECTIVE: To determine whether circulating serum levels of soluble interleukin-2 receptor (sIL-2R) are elevated in patients with localized scleroderma, and if levels of sIL-2R can differentiate between active and inactive disease. METHODS: Seventeen patients with localized scleroderma were categorized by overall physician assessment into active, inactive, and indeterminate groups, according to disease activity. Serum sIL-2R levels were analyzed and correlated with disease activity. RESULTS: The mean sIL-2R level was significantly higher (P = 0.005) in those with active disease (1,675 +/- 823 units/ml) than in those with inactive disease (722 +/- 218 units/ml). CONCLUSION: Serum sIL-2R levels are elevated in patients with localized scleroderma. When present, elevated sIL-2R levels appear to be able to differentiate active from inactive disease. This fact also suggests cell-mediated immune activation in this condition. Further serial studies are required to assess the value and sensitivity of sIL-2R levels in measuring changes in disease activity. PMID- 8003063 TI - Racial differences in the distribution of systemic sclerosis-related serum antinuclear antibodies. AB - OBJECTIVE: To determine racial differences in the frequencies of systemic sclerosis (SSc)-related serum antinuclear antibodies (ANA). METHODS: We tested serum samples from 275 Japanese, 416 North American Caucasian, and 24 North American black SSc patients for 8 SSc-related serum ANA, using indirect immunofluorescence, double immunodiffusion, and radioimmunoprecipitation assays. RESULTS: In comparing the 3 racial groups, we found that anti-U1 RNP, anti-RNA polymerase I, II, and III, and anti-U3 RNP antibodies were the most frequently detected antibodies in Japanese, Caucasian, and black patients, respectively. Anti-PM-Scl antibody was found exclusively in Caucasians. CONCLUSION: The production of SSc-related serum ANA is related to immunogenetic background. PMID- 8003064 TI - Treatment of stiff-man syndrome with intravenous immune globulin. AB - OBJECTIVE: To evaluate the efficacy of intravenous immune globulin (IVIG) in the treatment of stiff-man syndrome (SMS). METHODS: An open, unblinded study of 3 patients with active disease and/or disease refractory to treatment with diazepam and/or corticosteroids. RESULTS: All 3 bedridden patients improved substantially shortly after infusion with IVIG and regained function. CONCLUSION: IVIG may be useful for the treatment of SMS. PMID- 8003065 TI - Influence of disease manifestation and antineutrophil cytoplasmic antibody titer on the response to pulse cyclophosphamide therapy in patients with Wegener's granulomatosis. AB - OBJECTIVE: To assess the effectiveness of pulse cyclophosphamide (CYC) in the treatment of Wegener's granulomatosis (WG) and to identify the patients who are responsive to the treatment. METHODS: The prospective study included 43 patients with biopsy-proven WG. Clinical, radiographic, laboratory, and immunologic data were evaluated for predictive values regarding the outcome of pulse CYC therapy. RESULTS: Only 42% of the patients showed complete or partial remission that lasted at least 6 months after cessation of pulse CYC therapy. These responders had a higher frequency of disease activity limited to the upper and lower respiratory tract (39%, versus 8% in the nonresponder group; P < 0.05) and had lower titers of classic antineutrophil cytoplasmic antibody (cANCA) prior to treatment (< 1:64 42%, versus 6% in the nonresponder group; P < 0.05). In the 58% of patients who did not respond to pulse CYC treatment, there was both systemic disease involving more than 4 organ systems (mainly, the heart, nervous system, eye, and skin) and constitutional symptoms. Serious side effects induced by pulse CYC occurred in only 1 patient. CONCLUSION: Based on these findings, pulse CYC therapy appears to be effective in WG patients with moderate disease activity and low titers of cANCA, but of little benefit in patients with severe WG. Pulse CYC should therefore not be used as first-line therapy in patients with severe and rapidly progressing forms of WG associated with high titers of cANCA. PMID- 8003066 TI - Modulation of helper T cell function by prostaglandins. AB - OBJECTIVE: To determine the influence of prostaglandins on the production of interleukins 2, 4, and 5 (IL-2, IL-4, and IL-5), interferon-gamma (IFN gamma), granulocyte-macrophage colony-stimulating factor, and transformating growth factor beta 1 by CD4+ T cells. METHODS: TH0, TH1, and TH2 T cell clones were stimulated in the presence and absence of the prostaglandin E1 (PGE1) analog misoprostol and PGE2. Lymphokine production was analyzed by using a semiquantitative polymerase chain reaction with lymphokine-specific primer sets and/or by determining lymphokine activity in bioassays. RESULTS: PGE2 and misoprostol have distinct effects on different functional T helper cells. TH1 cells, which predominantly produce IL-2 and IFN gamma, are completely inhibited, while TH2 cells, which preferentially produce IL-4 and IL-5, are largely unaffected. Misoprostol and PGE2 are equivalent in their ability to modulate T cell function. In the presence of prostaglandins, TH0-like helper cells, which are characterized by the coproduction of multiple lymphokines, function as TH2 cells; however, they do not differentiate into TH2 T cells. CONCLUSION: Prostaglandins that are produced in inflamed tissue can regulate the functional capabilities of infiltrating T cells. In the presence of PGE2, TH1-like responses are suppressed and TH0-like responses are shifted toward a TH2-like pattern dominated by the production of IL-4 and IL-5. Inhibition of prostaglandin production by antiinflammatory agents might restore TH1 responses with local production of IL-2 and IFN gamma. PMID- 8003067 TI - Causal link between nucleotide pyrophosphohydrolase overactivity and increased intracellular inorganic pyrophosphate generation demonstrated by transfection of cultured fibroblasts and osteoblasts with plasma cell membrane glycoprotein-1. Relevance to calcium pyrophosphate dihydrate deposition disease. AB - OBJECTIVE: In subjects with idiopathic calcium pyrophosphate dihydrate (CPPD) deposition disease, cartilage chondrocytes elaborate increased amounts of PPi. The mechanism of the intracellular PPi elevation is not known. Plasma membrane 5' nucleotide phosphodiesterase I/nucleotide pyrophosphohydrolase (NTPPPH) activity also is elevated in chondrocytes and dermal fibroblasts of patients with idiopathic CPPD deposition disease. NTPPPH, as an ecto-enzyme, could act within certain intracellular compartments. Thus, we hypothesized a potential causal link between increased NTPPPH activity and increased intracellular PPi. METHODS: Transformed simian fibroblasts (COS cells) and human osteoblasts (U2OS cells) were transfected with the 5'-nucleotide phosphodiesterase I ecto-enzyme plasma cell membrane glycoprotein-1 (PC-1), recently shown to be expressed in cartilage, osteoblasts, and fibroblasts. RESULTS: Transfection with PC-1 markedly up regulated 5'-nucleotode phosphodiesterase I activity and increased intracellular PPi concentrations by increasing the capacity of cells to generate PPi. Importantly, this did not require supplementation with exogenous nucleotides. CONCLUSION: Cellular overexpression of PC-1 produces NTPPPH overactivity and increased intracellular PPi generation in vitro. These findings support the potential importance of NTPPPH overactivity in PPi generation, both inside and outside the cell, in some subjects with CPPD deposition disease. PMID- 8003068 TI - Comparative inhibitory effects of bucillamine and D-penicillamine on the function of human B cells and T cells. AB - OBJECTIVE: Clinical trials have suggested that the efficacy of bucillamine (BUC) in rheumatoid arthritis (RA) may be superior to that of D-penicillamine (DP), although the basis of the differences remains unclear. Previous studies have revealed that BUC has unique immunomodulatory effects that depend upon its capacity to form an intramolecular disulfide (BUC-ID). We therefore examined the effects of BUC-ID on the in vitro function of human B cells and T cells compared with those of DP, at their pharmacologically attainable concentrations. METHODS: IgM production was induced in highly purified B cells from healthy donors by stimulation with Staphylococcus aureus Cowan 1 (SAC) plus interleukin-2 (IL-2) or with immobilized anti-CD3-activated CD4+ T cells. Interferon-gamma (IFN gamma) production was induced in CD4+ T cells by stimulation with immobilized anti-CD3. RESULTS: BUC-ID suppressed IgM production induced by SAC+IL-2 as well as that induced by immobilized anti-CD3-activated CD4+ T cells, whereas DP suppressed the latter more markedly than the former. DP (3 micrograms/ml) significantly suppressed IFN gamma production by immobilized anti-CD3-stimulated CD4+ T cells, but not IgM production induced by SAC + IL-2 stimulation. By contrast, BUC-ID (0.3 microgram/ml) significantly suppressed IgM production induced by SAC + IL-2, but not T cell IFN gamma production. Of note, BUC-ID did not suppress IL-6 production by SAC-activated B cells. CONCLUSION: These results indicate that the target cells of BUC and DP in vivo might be different, with the former inhibiting the function of B cells and the latter that of T cells. The data suggest the possibility that BUC may have a different effect in RA patients compared with the effect of DP, and may be effective in patients who do not respond to DP. PMID- 8003069 TI - Human T lymphocytes express a member of the Matrix Metalloproteinase gene family. AB - OBJECTIVE: T lymphocytes are known to interact with cellular and structural components of the extracellular matrix. We investigated whether T lymphocytes could also contribute to matrix breakdown by expression of a matrix metalloproteinase (MMP) gene. METHODS: Complementary DNA (cDNA) was synthesized from messenger RNA extracted from cultured peripheral blood T lymphocytes after exposure to phorbol myristate acetate and calcium ionophore A23187 and amplified by the polymerase chain reaction with primers derived from two conserved domains in MMP genes. RESULTS: An amplification product of 402 basepairs was generated and cloned; sequence analysis revealed identity to human stromelysin-2 cDNA. Using the amplified stromelysin-2 cDNA as a probe for Northern analyses, we detected a 1.8-kilobase transcript in stimulated T lymphocytes. CONCLUSION: T lymphocytes are a potential source of stromelysin-2 transcripts and may have a role in the degradation of extracellular matrix constituents. PMID- 8003070 TI - Cutaneous signs of rheumatic disease: acral purpuric papules in a patient with clinical rheumatoid arthritis. PMID- 8003071 TI - Reactive arthritis associated with Hafnia alvei enteritis. PMID- 8003072 TI - "Pseudo" meralgia paresthetica. PMID- 8003074 TI - Perspectives on aging. PMID- 8003073 TI - Association of anti-Ro/SS-A autoantibodies with glutamine in position 34 of DQA1 and leucine in position 26 of DQB1. PMID- 8003075 TI - Looking toward the next millennium. PMID- 8003076 TI - The educational imperative. PMID- 8003077 TI - Research directions. PMID- 8003078 TI - Early intervention and health care reform. PMID- 8003079 TI - Let me tell you about my aphasia. PMID- 8003080 TI - What older consumers think. PMID- 8003081 TI - The service delivery continuum. PMID- 8003082 TI - Three generations of ASHA members. PMID- 8003083 TI - Multicultural aspects of aging. PMID- 8003084 TI - Benefits of breastfeeding. PMID- 8003085 TI - What costs for better health care? PMID- 8003086 TI - Who speaks for audiologists? PMID- 8003087 TI - Children and bilingualism. PMID- 8003088 TI - Extravascular circulation of lipoproteins: their role in reverse transport of cholesterol. AB - The transfer of lipoproteins out of plasma into peripheral tissues, their flow through the interstitium and their return to blood has been reviewed. In this context special emphasis has been given to reports dealing with the movement of lipoproteins into and out of the wall of arteries. PMID- 8003089 TI - The adventitia and atherogenesis: removal initiates intimal proliferation in the rabbit which regresses on generation of a 'neoadventitia'. AB - Removal of the carotid artery adventitia from rabbits induced the formation of an intimal hyperplastic lesion. In rabbits fed a normal diet, the lesion (measured as the intimal:medial ratio) was maximal by day 14 (0.456 +/- 0.079, n = 5, P < 0.01) and thereafter, regressed towards control dimensions (0.037 +/- 0.003, n = 14) by day 28 (0.080 +/- 0.025, n = 7, P = 0.14). In rabbits fed a high cholesterol diet, the lesion was again maximal by day 14 (0.376 +/- 0.056, n = 8, P < 0.01). Although some regression was seen, the lesion persisted to day 42 (0.272 +/- 0.052, n = 8, P < 0.01). Electron microscopy and immunocytochemistry showed two types of lesion, (a) smooth muscle cell predominant on normal diet and, (b) macrophage predominant on high cholesterol diet. Smooth muscle cell predominant lesions underwent almost complete regression, whereas macrophage predominant lesions persisted. We propose that lesion formation may be initiated following the development of arterial wall hypoxia, secondary to excision of the adventitial vasa vasorum. Furthermore, we have devised a novel method to restore a highly vascular 'neoadventitia' to an artery whose adventitia has previously been removed, using loosely placed PVC tubing. We suggest this 'neoadventitia' was able to inhibit the formation of an intimal hyperplastic lesion and to promote regression of an already established lesion by restoring arterial wall oxygenation. PMID- 8003090 TI - Selective uptake of high-density lipoprotein-associated cholesteryl esters and high-density lipoprotein particle uptake by human monocyte-macrophages. AB - High-density lipoprotein (HDL) cholesteryl esters (CE) are taken up by many cells without parallel uptake of HDL apolipoproteins. This selective uptake of HDL CE was investigated in human monocyte-derived macrophages (HMM). HDL3 (d = 1.125 1.21 g/ml) was labeled in its apolipoprotein A-I moiety with 125I and in its CE moiety with [3H]cholesteryl oleyl ether. Cultured human monocyte-macrophages were incubated in the presence of doubly labeled HDL3 followed by determination of tracer uptake. HMM took up HDL3 particles as indicated by the uptake of HDL3 apolipoproteins. Uptake of HDL3-associated CE tracer was in significant excess of that due to HDL3 particle uptake indicating selective uptake of CE. Increased cell cholesterol due to preincubation with acetylated low-density lipoprotein (LDL) down-regulated selective uptake by HMM. According to several experimental approaches, selective uptake of HDL3 CE was independent from cell-secreted products, LDL receptor-mediated endocytosis or HDL3 retroendocytosis. The intracellular catabolism of HDL3 CE was investigated with HDL3 labeled in its CE moiety with [3H]cholesteryl oleate. The lysosomal inhibitor chloroquine had no effect on CE hydrolysis indicating that CE selectively taken up is hydrolyzed independently from lysosomes. In conclusion, HMM selectively take up HDL3 associated CE. The cellular mechanism of selective uptake is independent from endocytosis or retroendocytosis. Intracellularly, HDL3 CE selectively taken up are catabolized independently from lysosomes. PMID- 8003091 TI - Sulfonylureas induce cholesterol accumulation in cultured human intimal cells and macrophages. AB - Using primary cultures of human smooth muscle intimal cells and mouse peritoneal macrophages it was demonstrated that oral hypoglycemic agents, sulfonylurea derivatives, at concentrations 10(-5)-10(-4) mol/l caused significant (by 25% 60%) intracellular total cholesterol accumulation. This in vitro atherogenic effect was confirmed in an ex vivo model. Sera from Type 2 diabetic patients, taken after sulfonylurea administration, acquired the ability to induce cholesterol accumulation in cultured cells. This enhanced atherogenic effect of patients' sera was observed for the next 2-4 h following the treatment and corresponded well to the pharmacokinetic characteristics of the tested drugs. The results suggest that sulfonylureas may exert a direct atherogenic action at the level of arterial cells, by increasing intracellular cholesterol content. PMID- 8003092 TI - Lipid peroxidation and homocysteine induced toxicity. AB - Homocysteine induced toxicity has been examined in cultures of human umbilical vein endothelial cells. The toxic effects of the amino acid alone and the amino acid plus Cu2+ could be prevented by catalase and decreased by desferal, when either was present in the culture medium. When desferal was allowed to accumulate intracellularly, no significant protection from homocysteine induced toxicity was observed. Even though lipid peroxidation accompanied the toxicity induced by homocysteine and homocysteine plus Cu2+, inhibition of lipid peroxidation in either case had no effect on cell viability. The significance of these results is discussed. PMID- 8003093 TI - Increase of high-density lipoprotein cholesterol at ovulation in healthy women. AB - Plasma cholesterol is believed to vary more in women than in men, with the menstrual cycle, yet our review of the literature found no consistent pattern. We examined variations in plasma lipoproteins in relation to ovarian hormones in 12 healthy, menstruating women. Twenty fasting blood samples were obtained on alternate days over one menstrual cycle; ovulation was timed by hormone measurements. Plasma was analysed enzymatically for total cholesterol (TC), high density lipoprotein cholesterol (HDL-C) and triacylglycerol (TAG). Low-density lipoprotein cholesterol (LDL-C) was estimated by the Friedewald formula. The greatest effect was seen in HDL-C. Concentrations increased by 12% (P < 0.001) between the times of menstruation and ovulation and remained elevated until the following premenstrual phase. The height of peak oestradiol concentrations at ovulation was significantly associated with HDL-C in that phase (r = +0.75, P < 0.01), and with mean HDL-C concentrations over the whole cycle (r = +0.65, P < 0.05). TC and LDL-C also increased at ovulation, by 9% (P < 0.005) and 11% (P < 0.025) respectively, although the effect was more transient. This study demonstrates that consistent changes in plasma lipoproteins do occur during the menstrual cycle. PMID- 8003094 TI - In vitro oxidised HDL is recognized by the scavenger receptor of macrophages: implications for its protective role in vivo. AB - To assess the effects of oxidative modification, human HDL was oxidised in vitro for 12 h (Ox-HDL12) and 24 h (Ox-HDL24) under similar conditions to those commonly used for LDL. The procedure resulted in: an increase in thiobarbituric acid reactive substances but with marginal change in electronegativity; protein denaturation accounting for 16% and 45% loss of immunoreactive apoprotein A-I in the Ox-HDL12 and Ox-HDL24 respectively relative to the non-oxidised, native HDL (Nat-HDL); a decrease in the polyunsaturated fatty acids of the triglyceride, cholesterol ester and phospholipid components of the lipoprotein; an increase in the proportion of short chain saturated fatty acids while the monounsaturated fatty acids remained relatively unchanged. Studies with human macrophages demonstrated: a decrease of 16% and 30% in the capacity of the Ox-HDL12 and Ox HDL24 respectively to efflux intracellular free cholesterol; 125I-Ox-HDL24 uptake and degradation was directly comparable with that of 125I-Ac-LDL; the addition of excess unlabelled Ox-HDL24, Ac-LDL, Ox-LDL24 and Nat-HDL resulted in 74%, 67%, 69% and 19% displacement of the 125I-Ox-HDL24 respectively; fucoidin and dextran sulphate displaced 125I-Ox-HDL by 20% and 40% respectively; intracellular free and esterified cholesterol was increased 2.5-fold and 4-fold respectively relative to Nat-HDL on incubation with Ox-HDL24. These findings suggest that HDL is susceptible to oxidative modification leading to recognition by the scavenger receptor of macrophages and subsequent intracellular cholesterol accumulation. As such, the in vivo protective role of HDL in cardiovascular disease can be reversed in those circumstances in which HDL, like LDL, undergoes oxidative modification. PMID- 8003095 TI - Adrenal androgens and testosterone as coronary risk factors in the Helsinki Heart Study. AB - We investigated the role of adrenal androgens, cortisol, testosterone and sex hormone binding globulin (SHBG) as coronary risk factors using a nested case control design. The study population consisted of 62 cases with cardiac end points and 97 controls on placebo during the last 4 years in the Helsinki Heart Study. Serum concentrations of dehydroepiandrosterone, dehydroepiandrosterone sulfate (DHEAS), androstenedione, androstanediol glucuronide, cortisol, testosterone, and SHBG at the first annual visit of the 5-year study period were determined by radioimmunoassays. The only significant difference was found in DHEAS, with cases having higher levels than controls (P < 0.04). DHEAS levels were positively associated with smoking (P < 0.001), alcohol consumption (P < 0.04) and triglyceride levels (P < 0.002) and with systolic (P < 0.04) and diastolic (P < 0.006) blood pressures, and negatively associated with age (P < 0.01) and HDL-cholesterol (P < 0.03). The association between DHEAS and the CHD risk was studied using logistic regression analyses with the classical risk factors--age, smoking, blood pressure, and lipid levels--as covariates in the models. Studies of the joint effects of age and DHEAS disclosed that the risk associated with elevated DHEAS was confirmed to older men (odds ratio (OR) 7.3, 95%, CI 2.3-23.3). A similar analysis with smoking revealed that the DHEAS related risk was mainly found in smokers (OR 3.4, 95% CI 1.5-8.2). One possible explanation for these results is that some form of mild steroid biosynthetic defect of the adrenals or functional adrenal hyperplasia associated with high DHEAS levels increases the CHD risk in this population. PMID- 8003096 TI - Prevalence of plaques and stenoses detectable by echo-Doppler examination in the femoral arteries of an elderly population. AB - Using echo-Doppler evaluation, we assessed the prevalence of possible atherosclerotic lesions in the common femoral arteries (n = 478) and superficial femoral arteries (n = 478) in 239 subjects (age range 65-94 years) living in retirement houses in Seattle. Ankle pressure was measured with a pneumatic cuff and a continuous wave Doppler. There were 68 individuals with an ankle arm index less than 0.97 and 39 of these with a index below 0.90. An echo-Doppler examination was performed with an Advanced Technologies Laboratories Mark 600 Duplex Scanner. We found 167 (34.9%) common femoral arteries affected by non stenosing plaque while 19 arteries (4%) had stenosis or occlusion. In addition, 178 (37.2%) superficial femoral arteries showed non-stenosing plaques. The subjects with common femoral disease were 27 (11.3%), those with evidence of superficial femoral artery disease were 48 (20.1%), and those affected by disease in both sites were 84 (35.1%). There were 80 people (33.5%) with no ultrasound evidence of femoral artery disease. We found that the presence and severity of disease increased progressively in the decades 65-74, 75-84 and 85-94. We also demonstrated a positive association between major cardiovascular risk factors and ultrasound evidence of peripheral disease. The prevalence of femoral artery disease in an apparently healthy population was relatively high, although stenoses in most instances were not severe.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8003097 TI - Body fat distribution and its association with metabolic and hormonal risk factors in women with angiographically assessed coronary artery disease. Evidence for the presence of a metabolic syndrome. AB - The aim of this study was to investigate the pattern of body fat distribution and its association with metabolic and hormonal cardiovascular risk factors in women undergoing coronary angiography. Thirty of the 51 women exhibited significant coronary artery disease (CAD) (group A), whereas the remaining 21 subjects were free of major coronary stenoses (group B). Twenty-five healthy women without clinical signs of CAD served as a control group (group C). Despite comparable age and body mass index the women of group A had a significantly higher waist-to-hip ratio (WHR), a measure of the pattern of body fat distribution, than those of group C (0.88 +/- 0.07 vs. 0.78 +/- 0.06, P < 0.01). In an oral glucose tolerance test a high prevalence of impaired glucose tolerance or diabetes was found in groups A and B (53% and 63%, respectively) compared with group C (4%, each P < 0.01). The women of groups A and B showed significantly higher blood pressure and triglyceride levels as well as lower HDL-cholesterol than those of group C, whereas total and LDL-cholesterol were not different between the groups. The serum concentrations of testosterone, sex-hormone-binding globulin (SHBG) and cortisol were comparable between the three groups and correlation analysis revealed positive associations between androgens and WHR (r = 0.36, P < 0.01) and serum insulin (r = 0.34, P < 0.01) respectively. These findings indicate that women with angiographically confirmed CAD, and those with clinical signs of CAD but without significant stenosis, frequently exhibit a metabolic syndrome characterized by a cluster of metabolic abnormalities which may underlie the atherosclerotic process. PMID- 8003099 TI - Regulation of apolipoprotein A-I gene expression by phenobarbital in the human hepatocarcinoma cell line, Hep3B. AB - Apolipoprotein (apo) A-I is the major protein constituent of plasma high density lipoprotein (HDL), which has been suggested to play a protective role against the development of atherosclerosis. The effect of phenobarbital on apo A-I mRNA and protein levels was studied in the human hepatoma cell line, Hep3B. Exposure of Hep3B cells to the drug (200 micrograms/ml) for 16 h resulted in a 4-fold and 8 fold increase in apo A-I mRNA and secreted protein levels, respectively. The induction of apo A-I mRNA level caused by phenobarbital could be due to increased rates of transcription and/or alteration in mRNA stability. To test these possibilities, nuclear run-off transcription assays and pulse-chase deinduction experiments were performed. We have demonstrated that phenobarbital treatment is associated with a 2-fold induction in apo A-I transcriptional activity. The estimated half-lives for apo A-I mRNA are 2 h and 3.6 h in the absence or presence of phenobarbital, respectively. The combination of increase in apo A-I transcription rate and mRNA stabilization could explain the 4-fold induction in apo A-I mRNA levels caused by phenobarbital treatment. However, these events could not be solely responsible for the 8-fold increase in secreted apo A-I protein level observed. The results suggest that the mechanism(s) by which phenobarbital induces apo A-I production operate at both pre- and either co- or post-translational mechanisms. The induction of apo A-I is specific since no significant alteration in apo E mRNA and proteins was observed in drug-treated cells. PMID- 8003100 TI - Could the identification of subclinical atherosclerosis offer an alternative to the mass drug treatment of hypercholesterolemia? PMID- 8003098 TI - Dietary sitostanol related to absorption, synthesis and serum level of cholesterol in different apolipoprotein E phenotypes. AB - Effects of small amounts of sitosterol, sitostanol and sitostanol esters (< 1 g/day of free sterols) dissolved in rapeseed oil (RSO) were studied on serum lipids and cholesterol metabolism in patients with primary hypercholesterolemia and different apolipoprotein E phenotypes on an RSO diet. One of the four groups was an RSO-fed control. Serum total and LDL cholesterol reductions were small in different plant sterol-fed groups, tended to be highest in the sitostanol ester group (-7%), but were significantly reduced by about 5% in the combined plant sterol groups. The reductions were -8% in the subjects with epsilon 4 allele and insignificant in those with apo E3/3 phenotype. Cholesterol precursor sterols in serum, markers of cholesterol synthesis, were increased only in the subjects with epsilon 4 allele. Cholesterol absorption was reduced by 7%, being 31% in the subjects with epsilon 4 allele, and fecal elimination of cholesterol was increased, a finding also indicating increased cholesterol synthesis. The changes in cholesterol absorption were related to those in fecal plant sterols (change in dietary intake) and serum total and LDL cholesterol (P = 0.04, 0.01 and 0.05, respectively). Thus, small amounts of dietary plant sterols (< 1 g/day), especially sitostanol esters dissolved in dietary fats, decrease serum total and LDL cholesterol by a proportional decrease in cholesterol absorption which, in turn, is associated with a compensatory increase in cholesterol synthesis. The effects are most consistent in subjects with epsilon 4 allele, but for effective hypocholesterolemic treatment dietary amount of sitostanol ester should exceed 1 g/day. PMID- 8003101 TI - Identification of the homozygous missense mutation in the lecithin:cholesterol acyltransferase (LCAT) gene, causing LCAT familial deficiency in two French patients. PMID- 8003102 TI - Interaction between transcription factors Sp1 and YY1. AB - A basal level of transcription is usually observed when all but a small region of DNA has been deleted from a eukaryotic gene promoter. These promoter elements, which are necessary and sufficient for specific transcription initiation, are referred to as minimal or core promoter elements. One element that is commonly present in a core promoter is the initiator. It has been demonstrated that the presence of Sp1 binding sites can greatly enhance the level of transcription initiation at initiator elements. A binding site for the YY1 transcription factor, located at the initiation site of the adeno-associated virus P5 promoter, functions as an initiator element; a synergistic enhancement of its activity is observed in vitro when upstream Sp1 binding sites are present. Here we report that this synergistic activation probably occurs through protein-protein interactions. PMID- 8003103 TI - Effects of [Ca2+]i and temperature on minK channels expressed in Xenopus oocytes. AB - Slowly activating, voltage-dependent minK channels cloned from rat kidney were expressed in Xenopus oocytes. Increase in the bath temperature from 22 to 32 degrees C resulted in a dramatic acceleration of minK channel activation. The extraordinarily high Q10 of minK channel activation was voltage-dependent, being higher at more negative potentials (Q10 at -20 mV; 7.02; at 20 mV: 4.0). While activation of minK channels was highly voltage-dependent at 22 degrees C, voltage had only little effect on minK channel activation at 32 degrees C. Increase in [Ca2+]i which has recently been shown to increase the maximal conductance gmax at room temperature, did not affect gmax at 32 degrees C. However, increase of [Ca2+]i caused acceleration of minK channel activation at both temperatures. The interaction of [Ca2+]i and temperature on gmax and activation rate of minK channels described here is very similar to recent findings on Ca- and temperature effects on the slowly activating potassium conductance IKs in guinea pig cardiac myocytes. PMID- 8003105 TI - Cardiac amyloidosis in the presence of Bence-Jones proteinuria and normal serum immunoglobulins. AB - We describe a case of cardiac amyloidosis, which is an uncommon cause of heart failure. This case is unusual, as the patient presented with symptoms of angina in the presence of normal coronary arteries and subsequently developed heart failure. Amyloidosis was secondary to myeloma with Bence-Jones proteinuria alone, which is rare. PMID- 8003104 TI - Glutamine peptide-supplemented long-term total parenteral nutrition: effects on intracellular and extracellular amino acid patterns, nitrogen economy, and tissue morphology in growing rats. AB - Glutamine (GLN) is a nonessential amino acid that is not included in current regimens for parenteral nutrition because of its chemical instability. This study tested the hypothesis that GLN supplementation during long-term total parenteral nutrition (TPN) (3 weeks) would enhance GLN availability, thereby improving nitrogen economy and growth in a growing rat model: Standard TPN delivering 300 kcal/kg per day (lipid:carbohydrate = 1.1) including 2.1 g of nitrogen per kilogram per day in an all-in-one solution was compared with an isonitrogenous, isocaloric, and isovolemic TPN regimen with 0.29 g of nitrogen per kilogram per day substituted by GLN derived from the dipeptides glycyl-GLN and alanyl-GLN (TPN GLN). Enterally fed controls were included. Analysis was confined to nonbacteremic animals with negative blood culture, in which extracellular and intracellular amino acid concentrations including GLN, nitrogen balance, serum protein concentrations, growth, and histologic sections of liver and small-bowel mucosa (light and scanning electron microscopy) were evaluated. Hepatic intracellular GLN concentrations were significantly lower, in animals receiving GLN-free TPN (11.7 +/- 1.6 nmol/mg fat-free dry and solid tissue mass, n = 9) compared with both GLN-supplemented TPN (16.0 +/- 3.0, n = 7) and enteral feeding (18.2 +/- 1.8, n = 6) (p < .001). Corresponding results were found for intracellular GLN concentrations in skeletal muscle (TPN standard 12.5 +/- 3.1, TPN GLN 14.7 +/- 3.1, enteral control 17.3 +/- 2.3, p < .05), intestinal mucosa, and spleen as well as for plasma concentrations.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8003108 TI - Eastern MA/Southeast PA physicians find reform tough but necessary. PMID- 8003106 TI - Validation of a breast cancer risk assessment model in women with a positive family history. AB - BACKGROUND: Gail et al. developed a statistical model for estimating the risk of developing breast cancer in white women screened annually with mammography. This model is used for counseling and for admission to clinical trials. PURPOSE: We evaluated the model prospectively in a cohort of women with a family history of breast cancer. METHODS: We followed women who participated in the American Cancer Society 1987 Texas Breast Screening Project. The model was evaluated by comparing the observed (O) and expected (E) numbers of breast cancers using composite background rates from both the Breast Cancer Detection and Demonstration Project and the Surveillance, Epidemiology, and End Results program of the National Cancer Institute. Data were partitioned by adherence to American Cancer Society screening guidelines. RESULTS: The Gail et al. model predicted the risk well among women who adhered to the American Cancer Society guidelines (O/E = 1.12; 95% confidence interval = 0.75-1.61) but overpredicted risk for women who did not adhere to the guidelines. There was an indication that the model overpredicted risk for women younger than 60 years old and underpredicted risk in women aged 60 years and older. CONCLUSIONS: Overall, the Gail et al. model accurately predicts risk in women with a family history of breast cancer and who adhere to American Cancer Society screening guidelines. Thus, the model should be used as it was intended, for women who receive annual mammograms. PMID- 8003107 TI - The organization of intercistronic regions of the aerobactin operon of pColV-K30 may account for the differential expression of the iucABCD iutA genes. AB - The complete nucleotide sequence of the 8.3 kilobase operon of the enterobacterial virulence plasmid pColV-K30, which encodes a high-affinity iron transport system mediated by the hydroxamate siderophore aerobactin, has been determined. The region includes five open reading frames which correspond to the genes iucA, iucB, iucC and iucD, encoding the enzymes of the biosynthetic pathway for aerobactin, and iutA for the outer membrane receptor of ferri-aerobactin complexes. The sequences of the iucABCD genes are tightly coupled without any intervening non-coding sequence. The predicted secondary mRNA structures at the gene junctions within the iucABCD cluster, along with their codon usage, may account for the differential expression of each of the protein products, as observed in vivo with minicells. The genes iucA and iucC, which determine the two subunits of the aerobactin synthetase complex, showed a considerable homology within three stretches of their amino acid sequence. A potential operator sequence (iron box) for the binding of the iron(II)-responsive Fur repressor protein was found within the iucA coding region, suggesting that the operon is subjected to an additional level of transcriptional repression by iron (II). PMID- 8003110 TI - A fund of relief. PMID- 8003109 TI - [Effect of intravenous glucose versus glucose-xylose (1:1) administration on carbohydrate and lipid metabolism after trauma and during infection]. AB - OBJECTIVE: To detect the effects of glucose-xylitol infusion versus glucose infusion alone on carbohydrate and lipid metabolism in postoperative stress and during sepsis. DESIGN: Prospective randomized study (study I after cardiac surgery) and intraindividual cross-over control study (study II in septic patients), respectively. SETTING: Intensive care unit of a university hospital. PATIENTS: 18 patients after aortocoronary bypass (ACVB) and 5 patients with sepsis. INTERVENTIONS: In study I during the first 24 postoperative hours one group (K I, n = 6) received glucose only (2 mg/kg BW/min), a second group (K II, n = 6) a mixture of glucose and xylitol (1:1; 2 mg/kg BW/min) and a third group (K III, n = 6) a glucose-containing electrolyte solution (0.8 mg/kg BW/min). Glucose, lactate, insulin and free fatty acid concentrations were measured pre- and postoperatively in 6-hour intervals over 36 h. In study II patients were firstly given 4 mg glucose/kg BW/min over 6 h, then infusion was changed to a 1:1 glucose-xylitol mixture (4 mg/kg BW/min) for another 6 h. Hepatic glucose production, palmitate oxidation rates and lactate concentrations were determined at the end of both infusion regimens. RESULTS: Glucose and insulin concentrations were significantly lower in K II and K III than in K I. The highest lactate values were observed 6 h postoperatively in K I. Concentrations of all fatty acids were lower in K I than in K II and K III during the infusion periods. In study II the glucose production and lactate values were significantly reduced during xylitol infusion, whereas palmitate oxidation rates were significantly increased when the infusion regimen changed from glucose to glucose-xylitol mixture. CONCLUSIONS: These data indicate that energetically ineffective high glucose concentrations were avoided and lactate production was diminished by infusion of glucose-xylitol in study I. In addition, xylitol achieved a higher endogenous release and oxidative utilisation of free fatty acids representing important fuel substrates after trauma and during sepsis. PMID- 8003111 TI - Birth outcomes following zidovudine therapy in pregnant women. AB - Approximately 100,000 childbearing-aged women in the United States are infected with human immunodeficiency virus (HIV), and an estimated 7000 infants are born to HIV-positive mothers each year. In the United States, the rate of perinatal transmission of HIV among mothers who do not receive antiretroviral therapy is 15%-30%. Results from a recent multicenter randomized double-blind clinical trial suggest that treatment of HIV-positive mothers and their infants with zidovudine (ZDV) may substantially reduce the risk for perinatal HIV transmission. However, any potential risk for adverse outcomes associated with use of antiretrovirals during pregnancy should be considered. This report summarizes data from the Antiretroviral Pregnancy Registry regarding use of ZDV and the occurrence of structural birth defects reported for pregnancies registered during January 1989 December 1993. PMID- 8003112 TI - Relation between alcohol intake, lipoproteins and coronary heart disease: the interest continues. AB - This paper reviews the much discussed association between alcohol intake, lipoproteins and coronary heart disease (CHD). Epidemiological studies have consistently shown an inverse trend between low to moderate alcohol consumption and CHD. Such a protective effect of alcohol against atherosclerosis has been associated with the elevated concentration of HDL-cholesterol induced by alcohol. However, the underlying mechanisms whereby alcohol drinking enhances HDL cholesterol levels are not yet fully clear. Various lifestyle variables, namely diet, smoking, hypertension, body mass index and exercise, can affect the lipoprotein status in both users and non-users of alcohol. PMID- 8003113 TI - Plasma lipids and alcohol consumption in alcoholic men: effect of withdrawal. AB - This study examines the effect of alcohol withdrawal on plasma lipids and particularly on HDL-cholesterol subfractions, in 18 middle-aged, clinically healthy but chronically drinking men, institutionalized for withdrawal therapy. Plasma lipids, total HDL and HDL3-cholesterol, Apo A-I and Apo B were assayed before and after 30-86 days of abstinence. A 38% decrease in mean total HDL cholesterol levels was observed after withdrawal therapy (P = 0.0002), and this was due mainly to a drop in HDL3-cholesterol concentrations (-43%, P = 0.0002). The decrease in HDL2-cholesterol concentrations was also significant (-21%, P < 0.005) but less marked. These results were not dependent on quantities of alcohol ingested before therapy, on duration of hospitalization and on changes in dietary fat intake or smoking habits. Apo A-I levels decreased (-39%, P = 0.0002) and the magnitude of the decrease after alcohol withdrawal was positively related to the duration of hospitalization. Apo B levels increased (+24%, P < 0.005). Among the anthropometric parameters, arm muscle area was significantly higher after alcohol withdrawal. The energy and macronutrient intakes did not significantly change during hospitalization. It is concluded that the modifications of HDL cholesterol, HDL3-cholesterol, HDL2-cholesterol Apo A-I and Apo B values were induced by alcohol withdrawal in this population of chronic french alcoholics. PMID- 8003114 TI - Evidence for the formation of multiple types of acetaldehyde-haemoglobin adducts. AB - Acetaldehyde readily reacted with red blood cells and isolated haemoglobin to form adducts. We examined acetaldehyde-haemoglobin reaction products, isolated from red blood cells incubated with acetaldehyde (AcH), for the presence of stable peptide-specific acetaldehyde adducts. Red blood cell incubations were with 20, 50, and 200 mM acetaldehyde for 3, 24 and 48 hr. Peptide-specific [14C]acetaldehyde modifications of Hb from each incubation were identified by tryptic peptide mapping procedures. Nine peptides had modifications and six were found in incubations with 20 mM acetaldehyde. Two of the peptides were acetaldehyde modifications of the Hb alpha- and beta-chain N-termini. Stability studies indicated that the remaining seven [14C]AcH-modified peptides did not result, as can occur under certain conditions, from the transfer of AcH on the N termini of Hb to N-termini formed after trypsin digestion. An analysis of the relative amounts of [14C]AcH-peptide adducts indicated that at least two of the seven peptides had reactivities for AcH different than the N-termini of Hb; that is, at least two modified peptides differ from imidazolidine-type adducts formed on the N-termini. The presence of multiple modifications with different sensitivities for AcH adduct formation may be useful in developing markers of alcohol consumption. PMID- 8003115 TI - Anti-acetaldehyde adduct antibodies generated by ethanol-fed rats react with reduced and unreduced acetaldehyde-modified proteins. AB - We have previously shown that rats fed ethanol for prolonged periods generate antibodies reactive with proteins modified by acetaldehyde in vitro. In this report we demonstrate that these antibodies react with two groups of adducts: those formed when acetaldehyde reacts with proteins at 37 degrees C for 24 hr ('unreduced' adducts) and those formed by a 1 hr incubation followed by the addition of sodium cyanoborohydride (a reducing agent specific for Schiff bases) to the reaction mixture ('reduced' adducts). These data suggest that adducts from both of these groups are formed in vivo as a result of ethanol ingestion by rats. PMID- 8003116 TI - Violent crime: the role of alcohol and new approaches to the prevention of injury. AB - Almost all evidence of a link between alcohol consumption and violence is available only in the form of aggregate data. This is unsatisfactory and case control investigations and studies which relate injury severity to blood alcohol levels are needed. In the few closely controlled studies which have been performed, increased risk of injury in assault has been linked with binge consumption of more than about 8 units, and above average weekly consumption only in those over 25 years. Raising the minimum purchasing age for alcohol to 21 years, learning to drink responsibly with parents, especially fathers, and the adoption of tempered glassware are all achievable objectives which would reduce alcohol-related injury. The use of sobriety-checkpoints (breath testing though not by the police) and other situational prevention programmes need to be evaluated in relation to reducing injury sustained in violent crime. Proactive, community policing has been shown to reduce levels of alcohol-related violent crime, in contrast to more reactive, defensive and confrontational policing. The concept of 'capable guardianship' to establish and maintain social control of young delinquents needs to be extended, particularly near known foci of violence such as bars and adjacent fast-food outlets and taxi-ranks. PMID- 8003117 TI - Reaction of 14C-acetaldehyde with whole blood in vitro: further evidence for the formation of unstable complexes with plasma proteins and red cells. AB - When heparinised whole blood was incubated with 5, 10, 45 or 180 microM 14C acetaldehyde for 1 hr, an average of 33%, 34%, 33% and 41%, respectively, of the radioactivity was associated with red cells and the remainder with plasma. Although 71-80% of the radioactivity in the plasma was TCA-precipitable, only 0.9 3.1% was non-dialysable after 48 hr of dialysis, indicating that much of the acetaldehyde was reversibly bound to protein. When blood was incubated with 10 180 microM 14C-acetaldehyde for 1 hr and the plasma subjected to Sephacryl S300 gel filtration, 0.3-1.9% of the added radioactivity was found in the albumin and IgG fractions; this radioactivity is presumed to reside in both unstable and stable acetaldehyde-protein adducts. Plasma derived from whole blood which was incubated with 5-180 microM acetaldehyde and dialysed for 24 hr displayed cytotoxic activity against A9 cells. These data indicate that when 14C acetaldehyde is incubated with whole blood, even at concentrations as low as 5-10 microM, a substantial proportion of the radioactive molecules form unstable cytotoxic adducts with plasma proteins and a much smaller proportion form stable adducts. Blood cells (mainly red cells) that were incubated with 14C-acetaldehyde were able to transfer radioactivity to cocultured K562 cells, supporting the possibility that not only acetaldehyde-modified plasma proteins but also acetaldehyde-modified blood cells may transport acetaldehyde and be cytotoxic in vivo. PMID- 8003118 TI - Red blood cell deformability and alcohol dependence in humans. AB - Studies of DPH fluorescence polarization and deformability have shown that alcohol induces rigidification of the red blood cell (RBC) membrane. We investigated a possible link between RBC membrane fluidity and deformability by studying both parameters simultaneously in samples from alcohol-dependent patients (group 1, N = 19), social drinkers (group 2, N = 12) and long-term abstaining alcoholics (group 3, N = 8). The active drinkers showed disturbances of several RBC membrane parameters, including abnormal microorganization of the membrane surface, a decrease in sialic acid content, and resistance to the fluidizing effect of ethanol, that were not completely corrected in the abstinent alcoholics. The RBC transit time was significantly longer in the active drinkers than in the abstainers but not the social drinkers. There were no significant differences between the groups with regard to membrane lipid core fluidity. The main abnormality (fluidization) in RBC from the active alcoholics involved the polar surface of the membrane (probed using TMA-DPH), and correlated with the decrease in sialic acid content but not with RBC deformability. PMID- 8003120 TI - A comparative study of alcoholic patients in Jos, Nigeria, and in Castrop-Rauxel, Germany. AB - A comparative study of the incidence of alcoholism and 175 associated psychopathological disorders, in 202 patients, was conducted in Castrop-Rauxel, F.R.G., and in Jos, Nigeria. The results of the study indicate that in relative terms the involvement of the females (36.6%) in Castrop-Rauxel was well over double the number in Jos (11.9%). The pattern of alcoholism in Jos was associated more with gradual personality deterioration rather than with the more frequent delirium tremens found in Castrop-Rauxel. The rate of hallucinosis and schizophreniform psychosis in Castrop-Rauxel were found to be more than double the incidence in Jos. Cases of depressive psychoses and suicidal ideas in Jos were double the incidence established in Castrop-Rauxel. A comparison of the gamma-GT of the two centres showed that in Jos 88.1% of the patients had pathological serum values compared with 61.4% in Castrop-Rauxel. This points to a higher frequency of liver impairment in the Jos cohort. The enzyme constellation established in this work is in correlation with clinical experience in Jos of a relatively higher level of terminal liver disease (cirrhosis) in patients with a history of alcohol misuse. PMID- 8003119 TI - A comparison of nutritional profiles of patients with alcohol-related pancreatitis and cirrhosis. AB - A multifactorial study of 58 variables of alcohol, dietary and tobacco habits of 106 chronic alcoholic and normal subjects was conducted over 2 years. The alcoholic population included subjects with either calcifying chronic pancreatitis (CCP) or cirrhosis (Ci). A standardized, previously validated questionnaire was used to investigate dietary intakes, drinking and smoking habits. The patients with CCP consumed a richer diet than those with Ci, consisting mainly of saturated fats and animals proteins. Although the alcoholics with CCP drank the same total quantity of alcohol as the alcoholics with Ci, they drank it over a shorter time period (less than 20 years) before diagnosis. Differences in the nutritional profiles of the two groups indicate that the population with alcohol-related digestive diseases is made up of subjects with different drinking and eating habits. These behavioural differences with respect to dietary and alcohol intake indicate that the alcoholic patients with CCP or Ci belong to different subgroups. PMID- 8003121 TI - Quantitative alterations after long-term alcohol administration in the dorsal lateral geniculate nucleus (dLGN) in the rabbit (Oryctolagus cuniculus). AB - The effects of chronic excessive alcohol ingestion on the central nervous system were studied in neurons of the dorsal lateral geniculate nucleus (dLGN) in the rabbit (Oryctolagus cuniculus). In this nucleus, neuron density and other morphometric parameters such as the somatic volume of the cells have been investigated both under normal conditions and under alcohol intoxication. Special attention was given to the possibility that positive somatic heteropycnosis may be a sign of imminent cell death. In addition, the percentage volumes occupied by normal neuronal soma and by affected cells were determined. Continuous alcohol treatment for 6 months reduced the size of certain types of neurons, the alteration being specially intense in areas with an abundance of larger neurons. In these areas more intense signs of somatic heteropycnosis also appeared. We discuss the relationship between the condition of the inhibitory neurons (GABAergic interneurons), the distribution of these in the lower zone of the nucleus, and their greater resistance to the influence of alcohol. This type of stereological analysis is intended to provide a better interpretation of the different degrees of the effects of alcohol, and to give more detailed information about changes at cellular level, both for comparative purposes with other situations and to shed light on the alterations caused by alcoholism. PMID- 8003122 TI - Abnormal ethanol metabolism in Long-Evans Cinnamon rats, a mutant strain developing spontaneous hepatoma. AB - The Long-Evans Cinnamon (LEC) rat is a mutant strain established from Long-Evans rats. LEC rats display hereditary hepatitis and spontaneous hepatocellular carcinoma (HCC). We first tried to examine effects of ethanol consumption on the development of HCC, and fed a Lieber's liquid diet containing 5% ethanol to LEC rats. However the rats died within 2 weeks because of acute alcohol intoxication. In LEC rats, the concentration of ethanol and acetaldehyde in blood was significantly higher, and liver alcohol dehydrogenase activity was slightly lower and acetaldehyde dehydrogenase activities were remarkably suppressed compared to those of Wistar rats. These results suggest that LEC rats have hereditary deficiencies of ethanol and acetaldehyde metabolizing enzymes. PMID- 8003123 TI - Studies on the incidence of hepatocellular carcinoma in heavy drinkers with liver cirrhosis. AB - The incidence of hepatocellular carcinoma (HCC) in heavy drinkers who drank more than 130 g per day for more than 10 years, and non-drinkers with cirrhosis who were positive or negative hepatitis C virus (HCV) markers, was analyzed in order to evaluate the effect of a large amount of alcohol on the development of HCC. A parallel study was also conducted in some patients from the aspect of HCV genotypes. Among 57 heavy drinkers with liver cirrhosis, HCV marker was positive in 36 patients (C+Al group) and negative in 21 patients (Al-alone group). Eighty one patients with liver cirrhosis of non-drinkers were positive for HCV markers (C-alone group). HCV infection was involved in 63% of heavy drinkers with cirrhosis and 44% of patients with HCC. The majority of HCC patients in the C+Al group was infected with HCV through routes other than blood transfusion. HCC developed at a younger age in patients of the C+Al group than in patients of the C-alone group without relation to history of blood transfusion. In more than a third of patients who had tattoos or used stimulants in the C+Al group, HCC developed without a history of blood transfusion. These results suggest that heavy drinking enhances the development of HCC. The HCV genotypes in patients with HCC were all type II, except for one case of type III and one unclassified. The mixed type of HCV was often found in patients who had a blood transfusion or tattoo, suggesting that there may be some correlation between the routes of HCV infection and the diversity of genotypes. PMID- 8003124 TI - Role of the aldehyde dehydrogenase-1 isozyme in the metabolism of acetaldehyde. AB - At least four types of aldehyde dehydrogenase (ALDH) isozymes exist in human liver: acetaldehyde (Ac-CHO) is metabolized mainly by ALDH2. However, the role of ALDH1 in Ac-CHO metabolism is not well known, because ALDH1 deficiency is rare. In the present study, changes in blood levels of Ac-CHO were analyzed in a person with ALDH1 deficiency who is also heterozygous for the ALDH2 alleles, and subjects with normal ALDH1, in order to clarify the roles of ALDH1 in the metabolism of Ac-CHO. By isoelectric focusing analysis of ALDH in red blood cells (RBC), the ALDH1 band was not detectable in a male subject, indicating ALDH1 deficiency. In this subject, ALDH1 activity was nearly null, but the activities in his wife and two children were normal. Serial changes of blood Ac-CHO levels following a small amount of ethanol were analyzed. The peak levels of Ac-CHO were not different between the subject with ALDH1 deficiency and the person with normal ALDH1. However, the decrease from the peak values of Ac-CHO was clearly slower in the deficient subject than in ALDH1 normal subjects. Changes in Ac-CHO in blood were also analyzed in vitro. Ac-CHO metabolism by RBC from the ALDH1 deficient subjects was clearly slower than in those from controls. These results indicate that ALDH1 plays an important role in the metabolism of Ac-CHO in blood. PMID- 8003125 TI - Genetic factors related to the development of carcinoma in digestive organs in alcoholics. AB - Heavy drinkers do not always develop alcoholic liver disease or cancer of the digestive organs, indicating that genetic factors may be involved. Recently, the presence of genetic polymorphisms of cytochrome P4502E1 (2E1) was confirmed. The genotype of 2E1 was separated into three types; type A which is homozygous for the c1 gene, type B which is heterozygous for the c1 and c2 genes, and type C which is homozygous for the c2 genes. In the present study the relationship between genotypes of 2E1 and digestive diseases, including alcoholic liver disease, was analyzed. In healthy controls, the prevalence of types A, B and C was 69%, 31% and 0%, respectively. In patients with esophageal cancer, four out of five patients (80%) were type B, and the prevalence of type B was significantly higher than that in normal controls. These results suggest that the c2 gene of 2E1 may be related to the development of esophageal cancer. In patients with gastric disease, the prevalence of types A and B was 72% and 28%, respectively. In patients with large bowel disease, the prevalence of type A was 83-100%, significantly higher than that in healthy controls. These results suggest that the c2 gene of 2E1 may not be related to the development of large bowel disease. However, the possibility should be considered that the c1 gene of 2E1 may link to its development. In this study, the relationship between the genotype of 2E1 and alcoholic liver disease was also analyzed. All patients with alcoholic liver disease, including one hepatoma, had the c2 gene but not the c1 gene. The frequency of the c2 gene was quite different from that in non-alcoholic liver disease.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8003126 TI - Serum level of carbohydrate-deficient transferrin as a marker of alcoholic liver disease. AB - Serum levels of carbohydrate-deficient transferrin (CDT) were assayed in 87 patients with alcoholic liver disease, 25 alcoholics without liver disease, 25 cases with viral liver disease and 37 healthy subjects, by two different methods (Pharmacia CDT RIA kit and Axis % CDT kit). The serum level of Pharmacia-CDT was significantly higher in the patients with alcoholic liver disease (38.9 +/- 2.8 U/l) compared to the normal subjects (18.9 +/- 0.2 U/l), alcoholics without liver disease (21.7 +/- 1.5 U/l) and non-alcoholic liver disease (viral liver disease) (23.4 +/- 1.6 U/l) (P < 0.001). The serum level of Axis-CDT was also significantly higher in the patients with alcoholic liver disease (4.22 +/- 0.48%) compared to the normal subjects (0.84 +/- 0.14%), alcoholics without liver disease (1.14 +/- 0.23%) and non-alcoholic liver disease (1.84 +/- 0.29%) (P < 0.001). A significant correlation was found between serum levels of CDT determined by the two kits (r = 0.718, P < 0.001). The serum level of Axis-CDT was significantly higher in patients with alcoholic hepatitis compared to the normal subjects (P < 0.005), while the serum level of Pharmacia-CDT was not increased in the patients with alcoholic hepatitis. These results indicate that determination of serum CDT levels is a useful marker of alcoholic liver disease, not a marker for alcohol consumption. Axis-CDT is more useful than Pharmacia-CDT for assaying the serum level of CDT in patients with alcoholic liver disease. PMID- 8003127 TI - The characteristics of alcoholics with HCV infection: histopathologic comparison with alcoholics without HCV infection and chronic type C hepatitis. AB - Out of 71 patients admitted to the National Kurihama Hospital and a related hospital for alcoholics or hepatic dysfunction, we studied the histopathology of alcoholics with HCV infection. Liver biopsies were divided into three groups depending on whether or not the patient was an alcoholic and anti-HCV antibody positive. The three groups were: (1) 30 HCV-antibody negative alcoholics, (2) 17 HCV-Ab positive alcoholics, and (3) 24 HCV-Ab positive non-alcoholics. Alcoholics developed specific hepatic fibrosis with a solid appearance, and the HCV-Ab negative alcoholics had relatively less lymphocytic infiltration. In contrast, patients with type C virus developed fibrosis with a loose appearance with more lymphocytic infiltrates including lymphfollicular accumulation. HCV-Ab positive alcoholics showed mixed features such as more fibrosis and less piecemeal necrosis and lymphocytic infiltration, especially in follicle formation, than HCV Ab positive non-alcoholics. Changes of hepatocytes, such as hydropic swelling, fatty change and acidophilic body, increased in severity in the alcoholics compared with the non-alcoholics with viral hepatitis. These findings suggest that the combined exposure to both alcohol and HCV enhances hepatocellular damage, but suppresses inflammatory reactions such as lymphocyte infiltration and follicle formation seen in type C hepatitis. PMID- 8003128 TI - Effects of alanine and glutamine administration on the inhibition of liver regeneration by acute ethanol treatment. AB - We studied the effects of alanine and glutamine administration on the inhibition of liver regeneration by acute ethanol treatment after partial hepatectomy (PH) in rats. When rats were dosed i.p. with ethanol at 2 g/kg at the time of PH, DNA synthesis 48 hr after PH was significantly inhibited, but it was completely reversed by the combined use of alanine and glutamine. Although hepatic ornithine decarboxylase (ODC) activity in the alcohol-treated group 4 hr after PH was significantly inhibited, there was a tendency towards recovery of the ODC inhibition in the alanine and glutamine-treated group. The putrescine (PUT) level in liver which was decreased by ethanol was also increased by the administration of alanine and glutamine. However, the levels of spermidine (SPD) and spermine (SPM) in liver were unaffected either by ethanol or by alanine and glutamine. These results suggest that alanine and glutamine show a protective effect on the inhibition of liver regeneration caused by acute ethanol treatment by improving polyamine metabolism, particularly by increasing hepatic PUT levels. PMID- 8003129 TI - Effect of alcohol on the functions of Kupffer cells and splenic macrophages in rats. AB - Uptake of endotoxin and production of tumor necrosis factor (TNF) by Kupffer cells and splenic macrophages were measured in chronically alcohol-fed rats. Twenty male Sprague-Dawley rats, weighing 200-250 g, were pair-fed by isocaloric control and ethanol-containing Lieber-DeCarli liquid diets for 6 weeks. Endotoxin uptake and TNF production of Kupffer cells and splenic macrophages in the chronic ethanol load-group were significantly (P < 0.001) greater than those in the control group. The increase in endotoxin uptake was more prominent in Kupffer cells and the increase in TNF production was more marked in splenic macrophages in the chronic ethanol group. When these cells were precultured in the medium containing 10-100 mM ethanol, the endotoxin uptake and TNF production of Kupffer cells isolated from control and chronic ethanol-fed rats were decreased in proportion to the concentration of ethanol in the culture medium. However, the addition of ethanol to the culture medium did not affect the endotoxin uptake and TNF production of splenic macrophages. These results support the hypothesis that the splenic macrophages are important for endotoxin uptake, and excessive production of TNF in rats given large amounts of alcohol. PMID- 8003130 TI - Investigation of alcohol dehydrogenase isozymes of biopsy gastric mucosa in Japanese. AB - Several milligrams of biopsy samples of the gastric mucosa from the body, the angulus and the antrum of the stomach from 32 Japanese (14 males and 18 females, 32-90 years old) were examined using isoelectric focusing combined with a sensitive and specific staining method for the detection of sigma-ADH isozyme variation. In addition, differences of isozyme activity were analyzed from the aspects of age and gender. The isozyme bands of sigma-ADH in regions of the body as well as the angulus showed detectable activity, but there was weak or no activity in the antrum in all 32 individuals. These observations were inconsistent with the previous report that sigma-ADH in polymorphic in the manner of presence or absence of isozyme bands in Japanese. sigma-ADH activity was higher in males than in females and decreased the higher age group. Consequently, sigma-ADH was not polymorphic in Japanese and the activity of sigma-ADH was influenced by factors such as anatomically distinct areas and ageing, as well as gender. PMID- 8003131 TI - Contribution of cytochrome P450s to MEOS (microsomal ethanol-oxidizing system): a specific and sensitive assay of MEOS activity by HPLC with fluorescence labeling. AB - The contribution of cytochrome P450s to MEOS (microsomal ethanol-oxidizing system) in rat hepatic microsomes was studied with a modified assay method for MEOS activity. Acetaldehyde produced by MEOS was converted into the fluorescent derivative with cyclohexane-1,3-dione and analyzed by HPLC with a fluorescence detector. Acetaldehyde production by hepatic microsomes of rats treated with ethanol was higher by 75% than that by control rats. Ethanol oxidation activity of eight forms of P450 was investigated in a reconstituted system. CYP1A2 and CYP2E1 had high rates of acetaldehyde formation. The Km value of CYP2E1 for ethanol oxidation was 9.48 mM, similar to that of hepatic microsomes from rats treated with ethanol. The Km value of CYP1A2 was higher than that of CYP2E1, indicating the CYP1A2 with lower affinity for ethanol compared with CYP2E1. From the results of an inhibition study with antibodies, CYP2E1 was found to be a main contributor to MEOS induced by ethanol in rats, but CYP1A2 was considered to play an important role for MEOS when CYP2E1 was not induced. These results present the possibility that CYP1A2 and CYP2E1 contribute to MEOS activity. PMID- 8003132 TI - Immunohistochemical demonstration of ethanol-inducible P450 2E1 in rat brain. AB - The microsomal ethanol-oxidizing system (MEOS) is a P450-dependent pathway for ethanol oxidation in hepatic microsomes. The bulk of MEOS activity is catalyzed by P450 2E1 (an ethanol-inducible isozyme of P450) in animal livers treated with ethanol. Rat brains also metabolize certain drugs, and it is theorized that a mechanism for drug metabolism exists within the brain which acts on P450. We compared immunohistochemical localization of P450 2E1 between ethanol-treated rats and pair-fed control rats. In control rats, immunoreactive P450 2E1 was detected in minute amounts in both basal ganglia and cerebellar cortices. After ethanol treatment, the content of P450 2E1 increased in the basal ganglia, and the enzyme was also induced in the cerebellar cortices, substantia nigra and hippocampus. We speculate that the rat brain metabolizes ethanol by P450 2E1. PMID- 8003133 TI - Effects of alcohol on the replication of hepatitis C virus. AB - We have reported that hepatitis C virus (HCV) RNA encoding the NS5 region (HCV NS5) became negative following abstinence in some patients with alcoholic liver disease (ALD). In order to clarify the relationship between alcohol misuse (abuse) and the replication of HCV, serial changes of HCV-NS5 and the titer of HCV (HCV-titer) in blood after abstinence were studied in 11 male patients with ALD. Disappearance of HCV-NS5 after abstinence was found in five out of 11 patients (45%) and HCV-titer in blood decreased in all of these cases. In one patient, HCV-NS5 became positive and HCV-titers increased again following resumption of alcohol misuse. The etiology of liver disease in heavy drinkers was subdivided into three categories: alcohol alone, alcohol and HCV, and HCV alone, according to the diagnostic criteria of the Japanese research group for ALD. The etiology in four patients was a combination of alcohol and HCV, and was HCV alone in the remaining seven patients. In all four patients of the alcohol and HCV group, and one out of seven patients in the HCV alone group, HCV-NS5 became negative and HCV-titer decreased after abstinence. The decrease in HCV-titer was not related to the HCV genotypes. These results suggest that alcohol misuse may enhance the replication of HCV. PMID- 8003134 TI - Effects of ethanol and acetaldehyde on the contraction of cultured Ito cells. AB - The effects of ethanol (Et-OH) and acetaldehyde (Ac-CHO) on the contraction of cultured Ito cells were studied using a time-interval videotape recorder (VTR). Ito cells were isolated from Wistar rats and cultured for 4 days. The motion of the cells was recorded by VTR and the sequential changes of the surface area of the each cell were evaluated by an image analyzer. No contraction of Ito cells was observed after incubation with Et-OH (100 mM) or Ac-CHO (500 microM) alone. Ten nanomoles endothelin-1 (ET-1) caused Ito cells to contract gradually. Pre incubation of ET-1 with Ac-CHO at 37 degrees C for 1 hr inhibited the contraction of Ito cells completely. This inhibition was not seen in pre-incubation of ET-1 with Et-OH. In addition, the Ito cells which were pre-cultured with Ac-CHO for 6 hr did not contract at all after incubation with ET-1. In the isoelectric focusing of ET-1, a band was clearly seen at pI 4.6 after the treatment with Et OH as well as non-treated ET-1. Two extra bands of ET-1 appeared in the anodic side of the gel after treatment with Ac-CHO, indicating the conformational changes of ET-1. These results indicated that the contraction of Ito cells induced by ET-1 was inhibited completely by Ac-CHO. This inhibitory effect of Ac CHO was thought to be caused by binding Ac-CHO to ET-1 itself or to ET-1 receptors. PMID- 8003135 TI - Roles of the splenic cytokines and arachidonic acid metabolites in severe hepatic injury after lipopolysaccharide injection in chronically alcohol-fed rats. AB - We examined the early changes after lipopolysaccharide (LPS) injection in chronically alcohol-fed rats with or without splenectomy. Administration of 2 mg/kg body weight LPS caused severe hepatic injury. The plasma aspartate aminotransferase (ASAT) activity was significantly higher in sham-operated rats 8 hr after LPS injection than in splenectomized rats. The plasma tumor necrosis factor (TNF) activity was also significantly higher 1 hr after LPS injection in sham-operated rats than in splenectomized rats. The plasma thromboxane (TX) B2/6 keto-prostaglandin (PG) F1 alpha ratio increased in sham-operated rats after LPS injection. Therefore, the balance of arachidonic acid metabolites was in a hypercoagulated state in sham-operated rats after the LPS injection. Neutrophil infiltration into liver tissue increased in sham-operated rats after the LPS injection. The cytokines and arachidonic acid metabolites released from the spleen after LPS injection in alcohol-fed rats may play important roles in severe hepatic injury. PMID- 8003136 TI - Clinical and pathological features, and the mechanism of development in severe alcoholic hepatitis, especially in comparison with acute type fulminant hepatitis. AB - Among the patients with alcoholic hepatitis, the patients with severe alcoholic hepatitis (SAH) were distinguished by clinical course, laboratory data and histological findings. The aim of this study was to clarify the clinicopathological features, pathological condition and pathogenesis of SAH. Twenty-four SAH patients were compared with 55 patients with acute type fulminant hepatitis (FH) and the other types of alcoholic liver disease. SAH showed a very poor prognosis with a survival rate of 25% and was complicated by multiple organ failure earlier than FH. IgA class lipid A antibody, endotoxin (Et) and tumor necrosis factor-alpha (TNF-alpha) levels in the blood well reflected the pathological condition and severity of SAH. The white blood cell count in the peripheral blood was thought to be the simplest indicator for the prediction of the prognosis of SAH. In conclusion, SAH involves hyper-endotoxemia due to dysfunction of the reticuloendothelial system in the liver, and cytokines including TNF-alpha and neutrophils play an important role in the severity of liver injury. PMID- 8003137 TI - Tibial tunnel placement in ACL reconstruction. AB - In reconstructing the ACL, ideal tibial tunnel placement requires an understanding of the unique anatomy of the ACL tibial footprint and its relationship to the PCL, lateral meniscus, and medial tibial part of the spine. In addition to precise placement of the tibial tunnel, its length and angulation are factors to consider. Using consistent anatomic landmarks with attention to detail, the tibial tunnel can be reproducibly placed in a manner that is not detrimental to the graft. PMID- 8003138 TI - Anatomy of the anterior cruciate ligament: a blueprint for repair and reconstruction. AB - The anterior cruciate ligament of the knee joint is a complex structure whose orientation, construct, and biology are directly related to its function as a constraint of knee joint motion. While the complexity of its design allows the ligament to function through the normal range of motion as a static stabilizer of the knee, it also makes the exact duplication of this structure very difficult. A fundamental knowledge of the functional anatomy of the anterior cruciate ligament provides the orthopaedic surgeon with an essential blueprint on which to base techniques of repair and reconstruction. PMID- 8003139 TI - Biomechanical function of the human anterior cruciate ligament. AB - Knowledge about the biomechanical function of the anterior cruciate ligament (ACL) is very important in the treatment of the ACL deficient knee. This article presents an overview of the biomechanical function of the ACL, including its structural and mechanical properties as well as its role in knee stabilization and normal kinematics. Tensile properties of the prospective biological grafts and future directions in ACL research are also discussed. PMID- 8003140 TI - Case report: revision anterior cruciate ligament reconstruction. AB - A case report is presented in which a professional football player, who was 4 years status post anterior cruciate ligament (ACL) reconstruction with autogenous patellar tendon, ruptured his graft. The contralateral patellar tendon was not available as a graft because of a more recent ACL reconstruction using that autogenous patellar tendon. This case reports the use of a previous donor site for supplying a patellar tendon autograft. Biopsy of the donor graft was consistent with normal tendon. The use of a healed patellar tendon donor site is a viable option for revision anterior cruciate reconstructive surgery. This option prevents the possibility of disease transmission with use of an allograft. We have shown grossly and histologically that the donor site has the potential to regenerate to tissue that has the appearance of normal tendon. This option could be available for revision surgery, but would not be recommended if the initial surgery was < 18 months-2 years in the past. PMID- 8003141 TI - Failure of arthroscopic decompression by subacromial heterotopic ossification causing recurrent impingement. AB - Heterotopic ossification is a well-recognized complication of musculoskeletal trauma and elective orthopaedic surgery. A series of 10 cases of arthroscopic subacromial decompressions developed postoperative heterotopic bone. In eight, the ectopic bone caused recurrent shoulder impingement. These are the first reported cases in which heterotopic ossification compromised the results of an arthroscopic procedure. It is recommended that the patient at risk (e.g., with active spondolytic arthropathy or a profile of hypertrophic pulmonary osteoarthropathy--obesity, diabetes with a history of chronic pulmonary disease) be considered for heterotopic ossification prophylaxis. PMID- 8003142 TI - Elbow arthroscopy for arthrofibrosis after type I radial head fractures. AB - The purpose of this study was to provide emphasis on recognizing arthrofibrosis as a potential complication of nondisplaced radial head fractures and the role of arthroscopy in its management. This series consists of five patients treated with arthroscopic debridement for arthrofibrosis after type I radial head fractures. Arthroscopy was considered only if the patient's range of motion had plateaued with significant residual loss of motion after an aggressive physical therapy program. Arthroscopy was performed an average of 6 months postinjury, and follow up averaged 24 months. The primary complaint was limitation of motion, especially extension, which was improved in all cases. A secondary complaint, painful crepitation, was also subjectively improved in all patients. There were no complications. Arthrofibrosis after type I radial head fractures is a well recognized entity. Arthroscopic debridement may be a useful adjunct in its management for patients with significant residual functional deficit after an aggressive conservative program. PMID- 8003143 TI - Generalized synovial chondromatosis of the knee: a comparison of removal of the loose bodies alone with arthroscopic synovectomy. AB - Thirteen patients with generalized synovial chondromatosis of the knee were treated by either removal of the loose bodies alone (n = 5) or arthroscopic synovectomy (n = 8). The average follow-up was 38 months (range 23-61). There were three recurrences in the loose body removal group, which were subsequently treated by arthroscopic synovectomy. Statistical analysis of the results shows a significant improvement in pain, synovitis and effusion, range of movement, and function after either treatment. The group treated by arthroscopic synovectomy had significantly lower recurrence rates (p = 0.02). We recommend arthroscopic synovectomy for patients with generalized synovial chondromatosis. However, if loose bodies alone are removed, a recurrence can be successfully treated by an arthroscopic synovectomy. PMID- 8003144 TI - Spontaneous hemarthrosis of the knee in the elderly: etiology and treatment. AB - The etiology of spontaneous hemarthrosis of the knee in elderly patients with osteoarthritis is still unknown. This report discusses six cases, one that was managed with conservative measures and five in which arthroscopic evaluation and treatment were performed. These patients were elderly individuals whose chief complaint was knee pain and swelling about the joint, without an obvious history of trauma. Each of the five operative patients underwent arthroscopic surgery after repeated hemorrhage into the joint that did not respond to serial aspirations of large amounts of blood and immobilization, using a knee immobilizer. The roentgenograms of each involved knee demonstrated lateral compartment osteoarthritis. Arthroscopic examination revealed a degenerative flap tear of the posterior horn of the lateral meniscus in the five operative cases. These patients underwent arthroscopic resection of the injured lateral meniscus and did not experience a recurrence of the hemarthrosis. The origin of the bleeding was most likely from the peripheral arteries of the posterior horn of the lateral meniscus. PMID- 8003145 TI - The diagnostic value and limitation of magnetic resonance imaging on chondral lesions in the knee joint. AB - Chondral lesions of the knee joint, which have been detected via arthrotomy or arthroscopy, were examined prospectively and retrospectively through a review of previously obtained magnetic resonance images (MRIs). The study group was composed of 34 men and 29 women whose average age was 24.6 years. Of these 63 patients, there were 72 articular cartilage lesions in 65 knees. On retrospective analysis, the sensitivity of MRI, which was defined as a true positive reading for softening, fragmentation, erosion, and/or a full-thickness loss of cartilage, was 14.3%, 57.3%, 75.0%, and 100%, respectively. Although the sensitivity to early changes of chondral lesions was low, indicating the limitation of MRI at the present stage, it has been demonstrated that MRI can delineate intracartilaginous changes associated with softening and thickening of cartilage that cannot be detected even with arthroscopy. Therefore, it may be worthwhile to perform an MRI as well as arthroscopy to clarify the pathogenesis of internal derangement of the knee. PMID- 8003146 TI - Hoffa's disease: arthroscopic resection of the infrapatellar fat pad. AB - In 11 patients the diagnosis of Hoffa's syndrome with chronic impingement of the fat pad was established by clinical signs and arthroscopic findings. Arthroscopic resection of the fat pad was performed. The patients were assessed using the Cincinnati rating system. There was a significant improvement in their symptoms and function after the surgery at an average follow-up of 76 months. The one poor result was in a patient who subsequently developed a diffused, chronic, inflammatory synovitis. PMID- 8003148 TI - The incidence of meniscal tears associated with acute anterior cruciate ligament disruption secondary to snow skiing accidents. AB - In the acutely traumatized knee, meniscal tears are commonly encountered with an anterior cruciate ligament (ACL) injury. Because of the high incidence of ACL injuries related to snow skiing, a retrospective study was conducted to determine the incidence and location of concomitant meniscal injuries in a series of 328 acute ACL tears resulting from snow-skiing accidents. Seventy-five (23%) of the ACL injuries had coexistent meniscal injuries--43 (13%) lateral and 32 (10%) medial menisci. Thirty-two (43%) of the 75 meniscal tears were peripheral detachments from the capsule (red-red tears), which often heal without surgical intervention. Findings from this study indicate that the incidence of meniscal damage in acute knee injuries secondary to snow skiing accidents is substantially lower than in knee injuries sustained during other sports activities, which range from 53% to 65% in previous studies. PMID- 8003147 TI - The effects of 4 Mrad of gamma irradiation on the initial mechanical properties of bone-patellar tendon-bone grafts. AB - Pairs of frozen human patellar tendon-bone (PTB) ligament allografts were exposed to either 0 or 4 Mrad of gamma irradiation sterilization, the latter value based on recent reports suggesting higher dosage levels for adequate sterilization against the human immunodeficiency virus. All specimens were subjected to three levels of loading: lower functional loads, higher functional loads, and failure. Lower functional loads were simulated by performing in vitro static and cyclic creep tests, similar to loads that the surgeon and patient would apply before and after implantation, respectively. Higher functional loads, simulating moderate activities of daily living, were represented by the slope of the linear portion of the force-elongation curve or linear stiffness. Failure or trauma was then simulated by failing the grafts in tension at a high strain rate. We found that the irradiation treatment shortened the tendon by only 0.6 mm, which was nevertheless statistically significant (p < 0.01). By contrast, 4 Mrad did not significantly alter either static or cyclic creep (p > 0.05) at lower functional loads. Instead, irradiation produced the greatest changes during failure testing, reducing both the graft's linear stiffness by 12% (p < 0.025) and maximum force by 26% (p < 0.001). Although our data do not describe how an allograft might perform during the early healing and later collagen-remodelling phases, such in vitro studies remain important if we are to optimize allograft properties before arthroscopic anterior and posterior cruciate ligament reconstruction. PMID- 8003149 TI - The effects of the neodymium laser on meniscal repair in the avascular zone of the meniscus. AB - Thirty mature New Zealand white rabbits were divided into four surgical groups, and a 3- to 4-mm incision was made in the inner avascular zone of the central third of the medial meniscus. In group I, the tear was not treated by lasering or suturing. In group II, the tear was sutured. Group III was given four different doses of the neodymium:yttrium-aluminum-garnet (Nd:YAG) laser irradiation with no suturing. Group IV underwent meniscal suturing followed by the same four different laser irradiation doses. The animals were killed at 2, 4, and 6 weeks, with gross and histologic evaluation of the healing responses by group and time. The overall results showed no healing of this meniscal tear in the avascular zone. Suturing generally showed increased cellular infiltration. The varying doses of the Nd:YAG lasing demonstrated no gradient effect, and no "welding" of menisci was noted. The maximum cellular inflammatory response was noted in the sutured and lased menisci, reinforcing the importance of a stable meniscal environment for healing meniscal tears. PMID- 8003150 TI - Accelerated rehabilitation for meniscus repairs. AB - Although meniscus tears suitable for repair are infrequent, meniscal repair is preferable to meniscectomy. Unfortunately, the postoperative restrictions commonly recommended preclude the athlete's rapid return to sports and can lead to the selection of meniscectomy over meniscus repair. Wide variations presently exist in the published postmeniscus repair rehabilitation programs. No objective assessment of these variables has been made to date. To assess the value of postoperative limits to motion, weight bearing, and agility activities, a comparison was made of our previously published "standard" rehabilitation program with an "accelerated" program permitting unlimited weight bearing, full motion, and no restrictions on pivoting sports. Group 1 (58 repairs), treated conventionally, had 11 failures (19%) at an average of 38 months postsurgery. The average age in group 1 was 23 years (range 14-45). Group 2, which included 40 repairs treated with the "accelerated" program, had four failures (10%) at an average follow-up of 20 months. The average age in group 2 was 26 years (range 15 40). Arthroscopic second looks were performed in 35% of group 1 and 25% of group 2. These data fail to show any statistical difference and do not support the need for activity restrictions after a meniscus repair. PMID- 8003151 TI - Arthroscopic repair of the ruptured meniscus: one to 6.3 years follow up. AB - Forty-nine patients underwent arthroscopic meniscal repair. Twenty-three had an isolated tear of the medial meniscus, four an isolated tear of the lateral meniscus, two a tear of the medial meniscus combined with a rupture of the medial collateral ligament, and 20 a tear of the anterior cruciate ligament (ACL) and a tear of one or both menisci. At the time of repair of the menisci, seven had undergone reconstruction of their ACL, whereas 13 had been treated conservatively for their ACL rupture. Seven of 10 retears were in patients with a conservatively treated ACL tear, and three were in patients with an isolated tear of a meniscus. Thirty-five patients without retears were reexamined after 5.5 years (1-6.3 years). The average Lysholm knee score before the trauma was 98 (range 75-100), and at follow-up it was 87 (range 29-100). The average Tegner's activity score before the trauma was 6 (range 3-9), and at follow-up it was 5 (range 0-9). When there is no retear, the clinical results of arthroscopic repair of the menisci are excellent. In those patients who had isolated lesions of the menisci, there were very few retears, 11% in this study. ACL deficiency of the knee greatly increases the risk of retear. In this study 46% of patients with persistent instability after an untreated ACL rupture incurred retears. There were no retears in the patients who underwent ACL reconstruction concomitant with the meniscal repair. PMID- 8003152 TI - Arthroscopic treatment of anterolateral ankle impingement. AB - Fifty-five ankle arthroscopies performed for anterolateral ankle impingement between January 1987 and April 1992 were reviewed for functional outcome and patient satisfaction. There were 33 men and 22 women with an average age of 34 years (range 20-67). All patients reported a previous history of ankle injury, and 60% of the patients had at least one ankle sprain. At an average follow up of 2.6 years (range 1.0-4.5), 87% of the patients had good/excellent results, 98% were satisfied, and 84% returned to their previous sports. PMID- 8003153 TI - Symptomatic intraarticular ganglia of the cruciate ligaments of the knee. AB - This case report draws attention to the clinical presentation, differential diagnosis, and recommended diagnostic modality and treatment of symptomatic ganglia of the anterior and posterior cruciate ligaments. One patient presented with a recurrent inability to fully extend the left knee. Another patient presented with pain and soreness over the lateral aspect of the knee, including the lateral joint line. The diagnosis of ganglia of the cruciate ligaments was made after clinical, radiographic, and magnetic resonance examination. Both patients were treated successfully with resection of their ganglia using arthroscopic techniques. PMID- 8003154 TI - The "arthroscopic impingement test". AB - Arthroscopic acromioplasty is an effective technique to treat refractory impingement syndrome of the shoulder; however, it is a technically demanding procedure and failure due to inadequate acromial resection has been reported. The purpose of this study was to describe a more reliable technique of arthroscopic acromioplasty ("arthroscopic impingement test") that allows determination of subacromial space available (SSA) during shoulder flexion after acromioplasty. During a 2-year period, 70 consecutive patients (group I) underwent arthroscopic acromioplasty by a conventional technique and 50 consecutive patients (group II) underwent the modified technique. Both groups were comparable in terms of age, gender, chronicity of symptoms, incidence of workman's compensation cases, side of surgery, and operative findings. In group I, four patients (6%) failed due to inadequate acromioplasty and at time of revision were found to have 0 mm SSA at 120 degrees flexion (contact of cuff on acromion). After revision acromioplasty, SSA at 120 degrees flexion was measured as > 3 mm, and impingement symptoms resolved postoperatively. In group II, there were no failures and SSA after initial acromioplasty was found to average 13 mm at 0 degree 10 mm at 45 degrees, 8 mm at 90 degrees, and 6 mm at 120 degrees flexion. In four cases, the "arthroscopic impingement test" determined that there was inadequate SSA at 120 degrees (< 3 mm) after initial acromioplasty, and these were revised by further acromioplasty at time of surgery. It was concluded that the "arthroscopic impingement test" improves reliability of arthroscopic acromioplasty by verifying adequate acromial resection in a position of impingement. PMID- 8003155 TI - Arthroscopic reduction and fixation of a completely displaced fracture of the intercondylar eminence of the tibia. AB - A simple method of arthroscopic reduction and fixation of a fracture of the intercondylar eminence of the tibia is described. A 23-year-old man with a completely displaced (Type IIIB) fracture was treated with arthroscopy. A satisfactory reduction was achieved by releasing the medial meniscus, which was entrapped in the fracture site. Link dynamic staples (W. Link, Hamburg, Germany) were used to firmly fix the fracture when the guide tube came downward from the medial mid-patellar portal. The secure fixation of the fragment and the prevention of the need for an arthrotomy facilitated early functional rehabilitation. One year after surgery the patient had a stable, painless joint with a full range of motion. The described method is technically straight-forward and can provide secure fixation of a bone fragment. The Link staples are useful in the fixation of a displaced fracture of the intercondylar eminence of the tibia. PMID- 8003156 TI - The freedom and the responsibility of investigator-initiated research. AB - Since World War II, scientific inquiry and research have been based on the premise that the more investigator-initiated research is conducted, the more automatic benefits for society are created. It is finally becoming clear to many that this belief is neither rational, true, nor healthy; in short, we as a society have been indiscriminately embracing whatever we are able to do instead of doing those things that will take society where it needs to go. Trickle-down science and technology do not work any better than the famous trickle-down economics worked. The author praises the accomplishments of scientific research but gives several examples, including those involving health care, of the widening gap that unguided science and technology have helped to foster between the advantaged and disadvantaged populations in most of the world, including the United States. He proposes that while investigator-initiated research is crucial, it must be done in the context of strategic paths and a set of values that direct it toward achieving the goals for the nation and the world that must be reached if the planet and its increasing population are to survive. He emphasizes that such strategic paths provide the compass; they do not control the journey. For example, he is not saying that biomedical researchers should be directed to specific experiments, but rather that as researchers they must realize the moving from remediation to prevention is a primary national and international goal for human health.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8003157 TI - The role of risk adjustment in national health reform. AB - Efforts to contain health insurance costs through competitive strategies are undermined by the economic incentive facing buyers and sellers to avoid high-risk individuals. To deal with this problem, proponents of competitive strategies, in which cost containment would be achieved by having consumers move to the most efficient health plans, suggest developing risk-assessment methods and using them to make transfer payments from plans enrolling relatively healthier people to plans with relatively sicker ones. Effective risk adjustment is also of interest to payers such as Medicare, large employers offering multiple-choice programs, and risk-bearing providers seeking fair compensation. So far, however, the ability to predict the variability of future medical costs on an individual basis is very limited. In a market in which individuals are free to change plans annually, the potency of current risk-adjustment technology would leave plans with ample incentive to attract healthier people and to avoid sicker people. The state of current risk-assessment methods leads some analysts to advocate a mixed payment system, partly based on a risk-adjusted prospective payment and partly based on retrospective adjustments made once competing plans' actual experiences are known. New York State is trying such an approach. Many analysts emphasize the importance of other insurance reforms and the institutional framework in which risk adjustments might be made as key factors in helping such a process succeed.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8003159 TI - Time to stanch the flow of residents. PMID- 8003158 TI - The research we should be doing. PMID- 8003160 TI - Sponsored research agreements: balancing risks and benefits. PMID- 8003161 TI - A relationship built on mutual distrust. PMID- 8003162 TI - Money talks: why debt and specialty choice are not strongly linked. PMID- 8003163 TI - Another view on CME's connection to medical school and residency education. PMID- 8003164 TI - Responses to "Problem-based learning: have the expectations been met?". PMID- 8003165 TI - Housestaff and faculty perceptions of patients' "teaching value". PMID- 8003166 TI - Students' psychosocial needs. PMID- 8003167 TI - Faculty and administration views of problems in faculty evaluation. AB - PURPOSE: To identify problems in how medical school faculty are evaluated, from the perspectives of faculty and administrators, and to understand how perceptions of the problems differ among those with varying roles within the medical school. METHOD: In March 1992 seven copies of an open-ended questionnaire were sent to each dean at the 126 accredited U.S. medical schools and 16 affiliated Canadian schools. The deans were instructed to complete one form themselves and to distribute one copy each to (1) a faculty affairs dean, (2) a basic science chair, (3) a clinical chair, (4) a member of chair of the school's promotion and tenure committee, (5) a senior faculty member, and (6) a junior faculty member. The authors conducted a content analysis of narrative comments in response to a question that began "Please identify and briefly describe the most salient problems you observe at your institution in how faculty are evaluated." RESULTS: Of a possible 994 responses, 455 (46%) were received. The respondents were from 102 of the 126 U.S. medical schools (81%) and eight of the 16 Canadian schools (50%). Response rates for the respondent subgroups ranged from 27% for the deans to 57% for the clinical chairs. Overall, the most frequently mentioned problems concerned the evaluation of teaching. General complaints about the inadequacy of current methods to evaluate teaching performance were most common--more than one in four respondents raised this issue--but the respondents also had specific complaints about student evaluations of teaching and the insufficient recognition given to teaching in the academic reward system. The frequencies with which other concerns were expressed tended to be related to the respondents' roles. These problems included concerns about the methods and measures used to assess research and scholarship and the quality of clinical care, the nonuniformity of evaluation processes and criteria for promotion among departments, the absence of regular evaluations, and the failure to link the results of evaluation to salary. CONCLUSION: The study population was not random; indeed, it was probably biased toward those who felt strongly (and perhaps negatively) about the current evaluation system. Still, the intensity with which views were expressed was striking. Improving the evaluation of faculty teaching undoubtedly remains one of medical education's greatest challenges. PMID- 8003168 TI - Association between rural hospitals' residencies and recruitment and retention of physicians. AB - PURPOSE: To analyze the association between rural hospitals' participation in residency training and their subsequent success in physician recruitment and retention. METHOD: The units of observation were 1,789 short-term, general hospitals that were located in nonmetropolitan U.S. countries, had medical staff information available, and did not close, open, or merge from 1985 through 1989. Multivariate analysis was done using ordinary least-squares estimation. The dependent variable was the change in the size of the medical staff at each hospital. Several characteristics of the hospitals and their counties were used as independent variables, the primary one being the number of housestaff at each hospital in 1985. RESULTS: The 66 rural hospitals that invested in housestaff were found to be more successful in physician recruitment and retention in subsequent years. On average, for every eight housestaff in 1985, each hospital gained approximately one additional physician on its medical staff from 1985 through 1989. CONCLUSION: The rural hospitals with residencies were more likely to be successful at recruiting and retaining physician staff than were the hospitals without residencies. Because most of the residencies were probably in primary care specialties, this finding is suggestive in light of the national need for primary care training as well as for successful recruiting strategies for rural hospitals. PMID- 8003169 TI - Effect of online literature searching on length of stay and patient care costs. AB - PURPOSE: To examine the associations between (1) the economic indicators of hospital costs, charges, and length of stay (LOS) for inpatient cases and (2) the use of MEDLINE searches for such cases. METHOD: An outcome-based, objective, prospective study with an economic evaluation was conducted from September 1989 to September 1990 at three metropolitan Detroit teaching hospitals representing both allopathic and osteopathic care. The study consisted of (1) 192 test cases, derived from a consecutive sample of inpatients of all ages for whom MEDLINE searches were requested at the participating medical libraries, and (2) 10,409 control cases, which were of the same diagnosis-related groups (DRGs) as the test cases but did not involve identified MEDLINE searches. Statistical analysis included the use of multivariate analyses of variance and correlation coefficients. Comparisons of cases were made on case-by-case and DRG bases regarding total patient costs, charges, and lengths of stay for cases with or without MEDLINE searches. RESULTS: The test cases were found to have a higher severity of illness. Among test cases, statistically significant relationships existed between (1) hospital expenses and LOS and (2) hospital expenses and the timing of the search during hospitalization when controlling for LOS. When cases were matched for DRG and LOS, the cases with early searches (i.e., conducted during the first half of hospitalization) had significantly lower expenses. CONCLUSION: Of the test-case patients (for whom MEDLINE searches were conducted during hospitalization), those whose searches were conducted earlier had statistically significantly lower costs, charges, and lengths of stay than those whose searches were conducted later. PMID- 8003170 TI - Effects of social support on medical students' performances. AB - BACKGROUND: Stress among medical students has been linked to poor academic performance, while supportive social relationships have been associated with the alleviation of psychological stress. This study examines social support as a potential buffer against stress and hence as a potential strengthener of students' academic performances. METHOD: A cohort of 153 third-year students at the University of Illinois College of Medicine at Chicago was asked in the fall of 1990 to complete a questionnaire assessing role stress (stress involving competing demands between school and social and/or family life), social support, and sources of support (outside or inside medical school). Grades for the five major clerkships through which all the students rotated during their third year were collected from student transcripts. Statistical analyses of the relationships among academic performance, stress, and social support included factor analysis, hierarchical multiple-regression analysis, and Pearson correlational analysis. RESULTS: Data from 120 students (78% of the cohort) were used for correlational analysis. Of these students, 79 (66%) were men and 41 (34%) were women. Because eight of the questionnaires contained incomplete data, 112 questionnaires (73%) were used for multiple-regression analysis. No buffering effect was found for social support. Rather, social support from outside the medical school explained significant variance in academic performances and in role stress. Higher levels of outside support were associated with poorer clerkship grades for women, but with lower levels of stress for men. Also, total support (outside and inside combined) was negatively related to clerkship grades for the entire sample. CONCLUSION: The results suggest that contrary to the study's hypotheses, social support in general is related to lower levels of academic performance for both men and women, and that the negative effects of support from outside the medical school context may be particularly salient for women. These results are understandable given the nature of medical training, which places great demands on students' time. Therefore, it may be more appropriate for medical schools to promote time-management strategies than support-building interventions, especially for women. PMID- 8003171 TI - Long-term follow-up of an alternative medical curriculum. AB - BACKGROUND: The Alternative Curriculum (AC), an elective program at the University of Virginia School of Medicine that enrolled a total of 48 students in 1973 and 1974, was one of many demonstration and pilot programs conducted during the 1970s. Its principal features were (1) a three-year time span; (2) early, prolonged, and intensive instruction in clinical skills; (3) intensive consideration of behavioral, social, economic, ethical, and legal aspects of medicine in a patient-centered curriculum; (4) an extensive course in sexuality; (5) an independent study format for two preclinical courses; (6) instruction in cardiopulmonary resuscitation; and (7) participation in the activities of the local rescue squad. In view of continuing questions about the structure and content of medical school curricula, it seemed worthwhile to try to determine what effects the program might have had on the participants during medical school and in their subsequent careers. METHODS: In 1991, data on the AC participants were collected, largely by means of a survey but also by examination of the participants' medical school records and determination of their current professional status. RESULTS: Of the 48 participants, 44 were available for the survey, and 37 returned completed questionnaires. The great majority of the respondents had positive opinions about the program's three-year time span, morale during the program, and beneficial effects of the program's special content during their clerkships, postgraduate training programs, and subsequent careers. They thought they had had enough time to make informed specialty choices and did not think that their participation in the AC had been a handicap in getting the internships they wanted. Fewer than half of the students thought that the AC had influenced their career choices, and only 26% were currently in primary care specialties. CONCLUSION: The AC was successful in improving students' morale during the preclinical segment, preparing them for clerkships, and increasing their sensitivity to the patient as a whole. That the program was not effective in inducing students to enter primary care specialties supports the view that curriculum content is not a major factor in students' choices of specialty. PMID- 8003172 TI - Career choices of minority high school student research apprentices at a health science center. PMID- 8003173 TI - Students' perceptions of course outcomes and learning styles in case-based courses in a traditional medical school. PMID- 8003174 TI - Results of the National Resident Matching Program for 1994. PMID- 8003175 TI - Roles for medical education in health care reform. Association of American Medical Colleges. PMID- 8003176 TI - The Veterans Health Administration: options for the future. Association of American Medical Colleges. PMID- 8003177 TI - Quinolizidine derivatives with antitubercular activity. AB - By reacting lupinylmagnesium chloride with suitable aromatic ketones, several lupinyldiarylcarbinols were obtained, whose dehydration gave the corresponding lupinylidenediarylmethanes. By reduction of three of these unsaturated compounds, the corresponding lupinyldiarylmethanes were also obtained. Direct condensation of lupinine with fluorene gave the 9-epi-lupinylfluorene. The quinolizidine derivatives obtained were tested against Mycobacterium tuberculosis H37RV. Nine compounds resulted endowed with good antitubercular activity with MIC < 8 micrograms/ml, while the remaining were only moderately active. Most interesting was the lupinylidene derivative 13 with MIC > 0.1 < 0.5 micrograms/ml. PMID- 8003178 TI - Rosmaricine derivatives as potential antitumoral agents. AB - A group of N-(alkylaminoacyl)-O,O-dimethylrosmaricines was prepared and, together with a set of rosmaricine derivatives previously described by us, evaluated for activity against lymphocytic leukemia P 388. Only one compound exhibited a borderline activity, while all the others were inactive. PMID- 8003179 TI - 1-Aryl-1H-pyrazole-5-acetic acids with antiinflammatory, analgesic and other activities. AB - Reaction of methyl 4-methoxy-2-dimethylaminomethylene-3-oxobutanoate with arylhydrazines gave methyl 1-aryl-5-(methoxymethyl)-1H-pyrazole-4-carboxylates 1 in high yields. Esters 1 were hydrolyzed to the relative carboxylic acids, which were converted by heating to 1-aryl-5-(methoxymethyl)-1H-pyrazoles 3 in good yields. Reaction of 3 with hydrobromic acid afforded the intermediate 1-aryl-5 (bromomethyl)-1H-pyrazoles, which were converted with potassium cyanide to 1-aryl 1H-pyrazole-5- acetonitriles, whose hydrolysis gave the required 1-aryl-1H pyrazole-5-acetic acids. Some acids 5 showed a strong antiinflammatory and analgesic activity in rats and mice, respectively, as well as moderate antipyretic and in vito platelet antiaggregating effects. PMID- 8003180 TI - Synthesis of 1-methyl-2,3-dimethyl-N(isopropyl)carbamates-4,5-dihydro-7-R'- 8-R 1H-benzo[g]indoles and evaluation of in vitro anticancer activity. AB - The synthesis of 7-mono or 7,8-disubstituted 4,5-dihydro-1-methyl-1H- benzo[g]indoles bearing a methyl-N-isopropylcarbamate group in position 2 or 2,3 of the pyrrole ring is described, in order to evaluate in vitro, anticancer activity. The preliminary results of this screening at the NCI of Bethesda showed a certain cellular subpanel selectivity between 10(-5) and 10(-4) molar concentrations. PMID- 8003181 TI - Synthesis and antimicrobial properties of N-substituted derivatives of (E)-alpha (or gamma)-azastilbenols. AB - The synthesis of 19 new N-substituted derivatives of (E)-alpha and gamma azastillbenols-2'(3' and 4') and their antimicrobial activity are reported. In particular, compounds 4a-4f and 6a showed good antibacterial activity against Staphylococcus aureus, Streptococcus faecalis, Bacillus subtilis and Escherichia coli. PMID- 8003182 TI - Synthesis and anticonvulsant activity of new 4- thiazolidone and 4-thiazoline derivatives. AB - A number of 2-(2-furoylhydrazono)-3-substituted 4-thiazolidone and 2-(2 furoylhydrazono)-3,4-disubstituted 4-thiazoline derivatives were synthesized and evaluated for anticonvulsant activity. Most of the tested compounds showed significant activity against MES induced seizures. PMID- 8003183 TI - Synthesis and antimicrobial activity of new 3,5-diaminoisothiazole derivatives. AB - The 3,5-diaminoisothiazole derivatives 23-42 were synthesized in excellent yields by oxidative cyclization of 3-amino-3-(dialkylamino)propenethioamide derivatives. These intermediates and the isothiazole derivatives were tested in vitro for their antimicrobial activity. PMID- 8003184 TI - 2-(Methyleneaminoxy)methylmorpholine derivatives. Synthesis and antidepressant activity. AB - The 3-(methyleneaminoxy)methylmorpholines 2 were synthesized as analogues of viloxazine 1, an antidepressant drug, in which the aryloxymethyl group is substituted by a (methyleneaminoxy)methyl moiety (MAOMM). Compounds 2 were tested as potential antidepressant agents by using the test of antagonism to reserpine induced hypothermy in mice. In addition, their anticholinergic and antihistaminic activity on isolated preparations and their ability to antagonize the toxicity induced by adrenaline in mice were evaluated. "In vivo" and "in vitro" tests showed that some compounds of type 2 possess a pharmacological profile similar to that of viloxazine 1. PMID- 8003185 TI - Tricyclic heteroaromatic systems. 2-Phenyl-1,2,4-triazolo[1,5-c][1,3]benzoxazin-5 one: a novel benzodiazepine receptor ligand. AB - The synthesis, unambiguous proof of structure and benzodiazepine receptor affinity and efficacy of 2-phenyl-1,2,4-triazolo[1,5-c][1,3]benzoxazin-5-one 1 are reported. The in vitro biological data indicate that 1 may be the lead compound of a new class of benzodiazepine antagonist-inverse agonist ligands. PMID- 8003186 TI - 2-Aryl-8-azaadenosines: structure-activity relationships in the binding with A1 and A2 receptors. A comparison with the corresponding 9-benzyl-8-azaadenines. III. AB - Several title compounds were assayed to determine their relative affinity towards the adenosine receptors. Selectivity ratios (SR) showed a prevalent A1 affinity. The comparison with the selectivity ratios of the corresponding 9-benzyl-8 azaadenines and the comparison between the affinity constant values (K1) for each receptor of the two series, were performed. The results led us to conclude that A1 receptors are characterized by more different arrangements which regard especially to 9-benzyl-8-azaadenines. PMID- 8003187 TI - N-[(N-halogenoacyl)imino]acenaphthene-quinoxalines as potential antitumoral agents. AB - Applying a reaction formerly studied by the Authors between acenaphthenequinone and N1-(2-amino)phenyl-N2-acylhydrazines, a group of N-[(N-alpha- and beta- halogenoacyl)imino]acenaphthenequinoxalines were obtained. On account of the reactivity of the halogen atom, they are potentially interesting as antitumoral agents. In contrast with the beta-chloropropionyl derivative, the alpha halogenoacyl derivatives were formed in low yields and with the simultaneous loss of the whole halogenoacylimino group. Thus, an alternative synthetic route was set up, consisting in the N-imination of acenaphthenequinoxalines by means of O mesitylenesulfonylhydroxylamine, followed by acylation of the intermediate N iminoacenaphthenequinoxalines. The National Cancer Institute of Bethesda evaluated the activity against lymphocytic leukemia P 388 on some of the numerous compounds now described. Only the N-chloroacetyliminoacenaphthenequinoxaline exhibited, at the dose of 50 mg/Kg i.p., 35% increase of the average survival time of treated mice. All the remaining compounds were inactive. PMID- 8003188 TI - Reassessing routines. PMID- 8003189 TI - A computerized system for analyzing occlusal relations during mandibular movements. AB - Articulators have long been used for analyzing occlusal relationships during mandibular movements. However, a comprehensive evaluation of occlusal relationships can be hindered by the instrument as well as the casts. Recent developments in computer technology avoid these limitations by providing the ability to visualize and analyze occlusion. The process is accomplished by recording occlusal form and mandibular movements optically and then digitizing them for computer use. The computer can generate a visual simulation of the patient's occlusion at any position during mandibular movement, which enables analysis of the articulation from any perspective. PMID- 8003190 TI - Titanium copings veneered with Procera ceramics: a longitudinal clinical study. AB - In 1989, 47 titanium copings veneered with a low-fusing ceramic were fabricated for 24 patients. Forty-four crowns could be examined after a period varying between 26 and 30 months. It was found that the bulk ceramic of two crowns had fractured. California Dental Association ratings for "Surface and Color" had changed markedly from the "Excellent" to the "Acceptable" level, and for "Anatomic Form" there was a small shift from the "Excellent" to the "Acceptable" level. The factor of "Margin Integrity" was recorded as "satisfactory" for all crowns and a large majority were rated "Excellent." PMID- 8003192 TI - The effect of custom tray material type and adhesive drying time on the tensile bond strength of an impression material/adhesive system. AB - The purpose of this investigation was to compare the tensile bond strength of one poly(vinyl siloxane) impression material/adhesive system to three different custom tray materials 10 minutes, 48 hours, and 7 days after adhesive application. One autopolymerizing (Fastray) and two light-polymerizing (Triad and Extoral) custom tray resins were examined. The Triad tray resin exhibited the significantly highest mean adhesive tensile bond strengths, and the Fastray resin exhibited the lowest. It was also observed that the 48-hour adhesive drying time group exhibited the highest mean adhesive tensile bond strengths for all the materials tested, and the 10-minute group exhibited the lowest. PMID- 8003191 TI - Characterization of the physical properties of resilient denture liners. AB - The physical and viscoelastic properties of two resilient denture liners, the polyphosphazine-based Novus and silicone-based Molloplast b, have been characterized. The two materials were found to have comparable tensile strengths and frictional properties but differed in their tear strengths, water sorptions, and solubilities. Novus had a greater tear strength and lower solubility, but greater water sorption, than Molloplast b. Compressibility studies indicated that significantly less force was required to compress 2- and 3-mm thicknesses of Novus by 0.2 and 0.4 mm than for Molloplast b. Dynamic mechanical analysis indicated that Novus should have a greater propensity for energy/impact absorption. PMID- 8003193 TI - Copy milling ceramic inlays from resin analogs: a practicable approach with the CELAY system. AB - The CELAY system for producing ceramic inlays and onlays using a resin pattern and copy milling is described. The mechanism uses no electronic assistance or imaging. Two different resin patterns are used, and direct and indirect techniques are described. All internal and external surfaces are reproduced by the technique. PMID- 8003194 TI - Implant treatment in partially edentulous patients: a report on prostheses after 3 years. AB - There has been an increasing interest in the use of implants for partially edentulous patients. This introduces other biomechanical situations than those experienced in completely edentulous patients. In a prospective multicenter study, 521 implants in 154 patients were loaded with 197 free-standing prostheses. The patients have been followed for 3 years. The cumulative success rate for the prostheses was 94.8% and for the implants it was 93.9%. Most of the lost prostheses were only supported by two implants. A frequent technical complication was fracture and loosening of gold screws, which was more frequent in prostheses supported by only two implants. PMID- 8003195 TI - Resistance to fracture of metal ceramic and all-ceramic crowns. AB - This study evaluated the fracture resistance of three types of all-ceramic crowns and compared these to the fracture values of metal ceramics. Uniform metal ceramic specimens; veneered, cast glass-ceramic; and porcelain fused to two different dispersion-strengthened ceramic cores (Hi-Ceram and In-Ceram) were investigated. The metal ceramic specimens demonstrated a significantly higher resistance to fracture than did the Hi-Ceram or veneered glass-ceramic units but did not significantly differ from the In-Ceram specimens. The metal ceramic crowns showed cracks only in the ceramic layer, whereas the all-ceramic specimens underwent global fracture. PMID- 8003196 TI - A study of the "thixotropic" property of elastomeric impression materials. AB - Shear-thinning, the decrease in the apparent viscosity of an impression material under a shear load, is a characteristic of many elastomeric impression materials and improves handling properties. However, it is unknown whether the subsequent viscosity of such material continues to be lower. This study compared the apparent viscosities of five elastomeric impression materials under two conditions. One group of the materials was manually spatulated and injected through an impression syringe before being tested; the other group of materials was manually spatulated only. It was found that the viscosities of these materials were not affected by the shear load applied during syringing. PMID- 8003197 TI - A predictive model for the polymerization of photo-activated resin composites. AB - This study investigated the relative significance of irradiation duration (20, 40, 60, or 80 seconds) and intensity; filler type (Silux Plus, a microfill or P 50, a hybrid); and shade (Universal or Gray) on the polymerization of resin composite within the depth of a simulated photopolymerized restoration. From the data, a mathematical model that predicts the extent of resin polymerization based upon the above stated variables was generated. The monomer conversion of specimens was determined by infrared spectroscopy. The results are of great clinical use and indicate that the most significant factor influencing resin composite polymerization is thickness of overlying resin composite. Both duration of exposure and light intensity demonstrate high and equal impact. Color and filler type have only minimal influence. The predictive model for resin composite polymerization provided a very good fit (r2 = .949). PMID- 8003198 TI - Finishing of MGC Dicor material. AB - The occlusal surfaces of inlays and onlays milled by the CEREC system are essentially flat, and surface morphology must be produced with rotary instruments. Six methods of finishing a machinable glass-ceramic material (Dicor MGC) were investigated using laser specular reflectance to assess the relative surface smoothness. The results indicated that all the methods produced a similarly smooth surface. PMID- 8003199 TI - A unified positional recording system for articulator setting. AB - This article describes the methods and materials used to easily and quickly capture excursive mandibular border movements. The novel method can be used for edentulous and dentulous patients and provides bilateral, three-dimensional record stability. It allows an uncomplicated method of setting a semiadjustable articulator. PMID- 8003200 TI - Fracture strength of three different core materials in combination with three different endodontic posts. AB - The purpose of this study was to determine the fracture load for three different core materials supported by three different post systems. The study was divided into nine separate groups, and each group comprised 10 samples. Specimens were placed in a special jig on a 45-degree angle, and the fracture load values were obtained using a universal testing machine. A 3 x 3 factorial two-way analysis of variance (P < .0408) was used to test the effects of core material and post type on the fractural resistance. Fracture load values (as measured in pounds) were: Flexi-Post/Ti-Core, 204.9; Vlock/Ti-Core, 218.8; Parapost/Ti-Core, 164.8; Flexi Post/Tytin, 156.0; Vlock/Tytin, 100.6; Parapost/Tytin, 134.6; Flexi-Post/Ketac Silver, 69.4; Vlock/Ketac-Silver, 50.4; and Parapost/Ketac-Silver, 37.7. The titanium composite, Ti-Core, had the greatest fracture load values in all instances; the silver-filled glass-ionomer specimen, Ketac-Silver, had the least. The Flexi-Post and the microthread, Vlock, had the greatest fracture load values, and the Parapost had the least. Both the Flexi-Post and Vlock post have large bulky heads with many vertical and horizontal grooves, apparently facilitating the locking of the core material into the post. PMID- 8003201 TI - Modification of a superficial X-ray therapy machine for rectal contact therapy. Preliminary results. AB - X-ray therapy of superficial rectal cancers using a hand-held 50 kV contact unit (Philips RT-50) in a technique first described by Papillon had reached a point of widening clinical acceptability when the manufacturer of this equipment discontinued its production. To pursue this endocavitary approach to rectal therapy, technical modifications have to be made to conventional superficial x ray therapy machines. Advantages over the original Papillon method include remote viewing of the lesion through the proctoscopic cone and a lower radiation exposure for the operator. We have evaluated a Bucky Combination Therapy Unit under conditions in which the operating voltage (65 kV), target skin distance (23.6 cm), and added filtration (0.39 mm Al) were selected in order to match as closely as possible the beam penetration characteristics of the "standard" (Papillon) technique. With this equipment, the thermal characteristics of the tube anode and housing limit the amount of radiation that can be delivered before a "rest period" for the machine is needed. In practice, 3 minutes of irradiation at an exposure rate of 500 R/min can be performed followed by an interval of 3 minutes before irradiation can be resumed. PMID- 8003202 TI - Beam attenuators and the risk of unrecognized large-fraction irradiation of critical tissues. AB - The use of radiation beam attenuators led to radiation injury of the spinal cord in one patient and of the peripheral nerve in another due to unsuspected large fraction irradiation. The anatomic distribution of radiation dose was reconstructed in the sagittal plane for the patient who developed radiation myelopathy and in the axial plane for the patient who developed peripheral neuropathy. The actual dose delivered to the injured structure in each patient was taken from the dose distribution and recorded along with the time, number of fractions, and dose per fraction. The patient who developed radiation myelopathy received a total of 46.5 Gy in twenty-three 2.1 Gy fractions in 31 days to the upper cervical spinal cord where the thickness of the neck was less than the central axis thickness due to cervical lordosis and absence of a posterior compensating filter. The patient who developed peripheral neuropathy received 55 Gy in twenty-five 2.2 Gy fractions in 50 days to the femoral nerve using bolus over the groins and an anterior one-half value layer Cerrobend pelvic block to bias the dose anteriorly. Compensating filters and other beam attenuators should be used with caution because they may result in unsuspected large-fraction irradiation and total doses of radiation that exceed the tolerance of critical structures. PMID- 8003203 TI - Matching electron beams without secondary collimation for treatment of extensive recurrent chest-wall carcinoma. AB - Matching electron beams without secondary collimators (applicators) were used for treatment of extensive, recurrent chest-wall carcinoma. Due to the wide penumbra of such beams, the homogeneity of the dose distribution at and around the junction point is clinically acceptable and relatively insensitive to positional errors. Specifically, dose around the junction point is homogeneous to within +/- 4% as calculated from beam profiles, while the positional error of 1 cm leaves this number essentially unchanged. The experimental isodose distribution in an anthropomorphic phantom supports this conclusion. Two electron beams with wide penumbra were used to cover the desired treatment area with satisfactory dose homogeneity. The technique is relatively simple yet clinically useful and can be considered a viable alternative for treatment of extensive chest-wall disease. The steps are suggested to make this technique more universal. PMID- 8003204 TI - Dosimetry of large, irregularly shaped fields by the circle method. A feasibility study. AB - The Circle Method is an algorithm for dose calculation in an irregularly shaped field. The algorithm is based on measurements of circle fields at the therapy machine in use. A separation into primary and scattered radiation components is not necessary. Clarkson's sector-integration method and an off-axis correction are embodied. Experimental and calculated dose values agree within +/- 2.8% in the treatment field and under block shieldings. PMID- 8003205 TI - Dosimetric characteristics of wedged fields. AB - The beam characteristics of the wedged fields in the nonwedged planes (planes normal to the wedged planes) were studied for 6 MV and 15 MV x-ray beams. A method was proposed for determining the maximum field length of a wedged field that can be used in the nonwedged plane without introducing undesirable alterations in the dose distributions of these fields. The method requires very few measurements. The relative wedge factors of 6 MV and 15 MV X-rays were determined for wedge filters of nominal wedge angles of 15 degrees, 30 degrees, 45 degrees, and 60 degrees as a function of depth and field size. For a 6 MV beam the relative wedge factors determined for a field size of 10 x 10 cm2 for 30 degrees, 45 degrees, and 60 degrees wedge filters can be used for various field sizes ranging from 4 cm2 to 20 cm2 (except for the 60 degrees wedge for which the maximum field size that can be used is 15 x 20 cm2) without introducing errors in the dosimetric calculations of more than 0.5% for depths up to 20 cm and 1% for depths up to 30 cm. For the 15 degrees wedge filter the relative wedge factor for a field size of 10 x 10 cm2 can be used over the same range of field sizes by introducing slightly higher error, 0.5% for depths up to 10 cm and 1% for depths up to 30 cm. For a 15 MV beam the maximum magnitude of the relative wedge factors for 45 degrees and 60 degrees lead wedges is of the order of 1%, and it is not important clinically to apply a correction of that magnitude. For a 15 MV beam the relative wedge factors determined for a field size of 6 x 6 cm2 for the 15 degrees and 30 degrees steel wedges can be used over a range of field sizes from 4 cm2 to 20 cm2 without causing dosimetric errors greater than 0.5% for depths up to 10 cm. PMID- 8003206 TI - Calibration of film for accurate megavoltage photon dosimetry. AB - An accurate method of converting film density to dose is presented. For films oriented parallel to the beam's central axis, calibration curves were produced at several depths using Kodak XV-2 film for cobalt-60, 4 MV, and 18 MV beams. Then the appropriate curve was employed to convert the film density to dose at a specific depth. It is hypothesized that the change in film response with depth is due to changes in the photon spectra at depth in a phantom. PMID- 8003207 TI - Dosimetric accuracy of a dual photon energy linac at low monitor setting for various pulse repetition frequencies. AB - Accuracy of dose delivery at low monitor unit setting is studied for a dual photon energy linear accelerator. Dose delivered per MU is found to be constant for both the photon beams for MU settings above 30. For lower MUs there is definite deviation from the calibrated value and the error is found to be increasing as fewer MUs are set for dose delivery. This dose/MU ratio at low MU setting is found to be dose-rate dependent, showing an increasing trend with pulse repetition frequency (PRF). Also, the dosimetric ratio is observed to be mode dependent; its value for an 18 MV beam is almost double that observed in the case of a 6 MV beam at very low MU setting. The magnitude of this error should be determined for each energy so that appropriate corrections can be applied if very low MUs are to be used. PMID- 8003208 TI - A measurement and analysis of buildup region dose for open field photon beams (cobalt-60 through 24 MV). AB - The central axis depth dose in the build-up region (surface to dmax) of single open field photon beams (cobalt-60 through 24 MV) has been measured utilizing parallel plate and extrapolation chamber methodology. These data were used to derive, for a prescription dose of 100 cGy, values of surface dose, the maximum value of dose along the central axis (Dmax) and the depth (nearest the surface) at which 90% of the prescription dose occurs (d90). For both single and parallel opposed pair (POP) open field configurations, data are presented at field sizes of 5 x 5, 15 x 15 and 25 x 25 cm2 for prescription depths of 10, 15 and 20 cm (midplane for POP). For the treatment machines, field sizes, and prescription depths studied, it is possible to conclude that: for single field irradiation, surface dose values (as a percentage of the prescription dose) can be either low (< 10%) or comparable to the prescription dose itself; for POP open fields, surface dose values are relatively independent of photon energy and midplane depth, and range between 30% and 70% of prescription dose, being principally dependent on field size; the depth of the initial 90 cGy point for a prescription dose of 100 cGy, d90, was larger for POP fields. For either single or POP open field treatments, d90 was always less than 22 mm, while for 6 MV or less, values of d90 were less than 4 mm; Dmax values can be very large (e.g., above 300 cGy) for certain treatment situations and are reduced significantly for POP treatments; for open field POP treatments, the percent reduction in Dmax with each increment in beam energy above 10 MV is reduced over that seen at 10 MV or less and, possibly, this further reduction may be clinically insignificant; for open field POP treatments, changes in surface dose, d90 and Dmax with beam energy above 10 MV do not suggest, with regard to these specific build-up curve parameters, any obvious advantage for treatment with beam energies greater than 10 MV for the specific machines and situations studied. PMID- 8003209 TI - [Application of cluster analysis to chemical taxonomy of medicinal material maidong]. AB - The cluster analysis shows that the phytochemical constituents in genera Ophiopogon and Liriope are obviously different from each other and even different species of the same genus are not quite similar. Being consistent with the result of the traditional morphological classification, the cluster analysis may provide a chemical evidence for the phytochemical taxonomy and identification of medicinal material Maidong. PMID- 8003210 TI - [A study on the relationship between the growth and yield of safflower under plastic mulching]. PMID- 8003211 TI - [GC-MS analysis of influence of processing on volatile oil in Daphne genkwa Sieb. et Zucc]. AB - The variation of volatile oils has been studied for GC-MS in different processed samples of Daphne genkwa. The results show that the contents of volatile oils in each processed sample are lower than these in the raw one, and the composition of those oils is greatly varied. The vinegar-fried and vinegar-boiled samples give more unknown ingredients. PMID- 8003212 TI - [Research on hemostatic mechanism of extracts from carbonized Schizonepeta tenuifolia Brig]. AB - It has been shown that StE can significantly shorten PT, TT, KPTT and RT of experimental animals and has an antiheparin function in the body. Meanwhile, it can significantly shorten ELT and strengthen FA. Its hemostatic action is accomplished through promoting coagulation and inhibiting fibrinolysis. 3P test and EG test were negative, it is thus impossible for a large dosage of StE to lead to DIC. PMID- 8003213 TI - [The decocting effect on crystal form and Ca/S value of gypsum fibrosum]. PMID- 8003214 TI - [The molecular structure of iso-aloesin isolated from the leaves of Aloe vera L. var. chinensis (Haw.) Berge]. AB - A new constituent iso-aloesin was isolated from the leaves of Aloe vera var. chinensis found in the Province of Guangxi. The molecular formula of iso-aloesin is C19H22O9, which is 2-acetonyl-6-C-beta-D-glucopyranosyl-7-hydroxy-5-methyl chromone. PMID- 8003215 TI - [Studies on chemical constituents of Smilax menispermoidea D.C]. PMID- 8003216 TI - [Studies on chemical constituents from solvent extracts of Poria cocos (Schw.) Wolf]. AB - Crystals I-N were isolated from the ethereal extracts of Poria cocos and identified respectively as O-acetyl-pachymic acid (I), 3 beta-hydroxy-lanosta 7,9(11),24-trien-21-oic acid (II), beta-amyrin acetate (III) and 3 beta-hydroxy 16 alpha-acetoxy-lanosta-7,9(11),24-trien-21-oic acid (N). Crystal III was obtained from P. cocos for the first time, and crystal N was newly discovered. PMID- 8003217 TI - [Studies on alkaloids of Thalictrum honanense W.T. Wang et S.H. Wang]. PMID- 8003218 TI - [Effect of tabellae Polygoni cuspidati on blood lipids and rheological property in rats]. PMID- 8003219 TI - [Effect of jingui shenqi pills on sex hormone in aged rats]. PMID- 8003220 TI - [Effects of the combination of Astragalus membranaceus (Fisch.) Bge. (AM), tail of Angelica sinensis (Oliv.) Diels. (TAS), Cyperus rotundus L. (CR), Ligusticum chuanxiong Hort. (LC) and Paeonia veitchii Lynch (PV) on the hemorrheological changes in normal rats]. AB - The results showed that AM and TAS had significant effects of enriching the blood. CR, a Qi-regulating drug, LC and PV, two blood-activating drugs, could improve all hemorrheological indexes, such as the whole blood specific viscosity, the plasma specific viscosity, erythrocyte electrophoresis, etc. The combination of Qi-regulating drug and blood-activating drug displayed more favorable effect. This experiment has provided some pharmacological evidence for the theory of "Qi Xue Xiang Guan" (correlation of vital energy with blood circulation) in traditional Chinese medicine. PMID- 8003221 TI - [Inhibition of aldose reductase by Chinese herbal medicine]. AB - Seven Chinese herbal drugs were screened for experimental inhibition of lens aldose reductase activity, among which quercetin exhibited potent enzyme inhibitory activities in vitro. Its IC50 value was 3.44 x 10(-7) mol/L. It may be helpful in the prophylaxis and treatment of diabetic complications. PMID- 8003222 TI - [Advances in the study of decoctions of Chinese herbal drugs and the reform of dosage forms]. PMID- 8003223 TI - [A review of the literature concerning the adverse effects of Chinese herbal drugs published in major medical and pharmaceutical periodicals in China in 1992]. PMID- 8003224 TI - [Revision on the type of leaf trace bundles of Cyperus rotundus L]. PMID- 8003225 TI - [Qualitative analysis of Chinese drug xiakucao (Prunella)]. AB - A high performance gas chromatographic procedure has been developed for the quantitation of ursolic acid and oleanolic acid in different parts of Xiakucao collected in different periods. The study provides a scientific foundation for increased availability and rational collecting periods of Xiakucao. PMID- 8003226 TI - [FeS2 changes in ignited pyritum]. AB - FeS2 changes in Pyritum during igniting process were studied systematically by comparing Pyritum ignited under different conditions in terms of S content, Fe content, yielding ratio of ignited product and appearance features. Calcined Pyritum samples purchased from various parts of China were also compared in regard to their quality. PMID- 8003227 TI - [Determination of ginseng total saponins in snow-frog tonic tablets]. PMID- 8003228 TI - [Studies on the alkaloidal components of Polygala tenuifolia willd]. AB - 1-Carbobutoxy-beta-carboline, N9-formylharman, 1-carboethoxy-beta-carboline, 1 carbomethoxy-beta-carboline, perlolyrine, harman and norharman were isolated from the rhizoma of Polygala lenuifolia. The structures were elucidated on the basis of spectroscopic studies and chemical evidence, 1-carbobutoxy-beta-carboline has not been seported before. PMID- 8003229 TI - [Studies on the chemical constituents of Epimedium acuminatum Franch]. AB - Five flavonoids were isolated from the aerial parts of Epimedium acuminatum. Their structures were determined chemically and spectroscopically to be baohuoside VI, tricin, icaritin, icariside I and baohuoside I. PMID- 8003230 TI - [Studies on polysaccharide of Rheum palmatum L]. AB - Two homogeneous acidic heteroglycans DHP-1 and DHP-2 were obtained from the root of Rheum palmatum, the mean molecular weights being 11 x 10(4) and 2.5 x 10(4) respectively. It was identified by TLC and GC that both heteroglycans contain the same main residues of glucose, galactose, arabinose, rhamnose, lyxose, xylose, glucuronic acid and galacturonic acid. PMID- 8003231 TI - [Studies on the chemical constituents of the herb huanghuaren (Sida acuta Burm. f.)]. AB - Seven constituents were isolated from the dry herb Huanghuaren. On the basis of spectroscopic analysis and physico-chemical constants four of them were identified as heraclenol, beta-sitosterol, acanthoside B and daucoglycoside. PMID- 8003232 TI - [Effects of seeds, leaves and fruits of Ziziphus spinosa and jujuboside A on central nervous system function]. AB - The seeds and leaves of Ziziphus Spinosa exert a similar inhibiting effect on central nervous system function, while the fruits have a synergism with pentobarbitol sodium and thiopental sodium on prolongation of sleep and sedation, also decreases coordinated action. Jujuboside A exerts no inhibiting effect, but a synergism with phenylalanine on central nervous system function. PMID- 8003233 TI - [Studies on the antitumor effect of Clerodendrum bungei Steud or C. foetidum Bge]. AB - Clerodendrum B(I) at dosage of 100g/kg ip or sc for 7 days was shown to have antitumor effect on hepatic carcinoma and sarcoma 180 in mice. In the mean time, 100g/kg sc of (I) interrupted 3H-TdR incorporation into DNA of sarcoma 180 cells in mice, 100, 10g/kg sc of (I) could suppress the phagocytic activity of the peritoneal macrophage against the CRBC (chicken red blood cells) in mice, 100g/kg sc of (I) also made the production of serum hemolysin less than one half of that of the control in mice immunized with SRBC. Clerodendrum C at 100g/kg could inhibit the growth of hepatic carcinoma in mice. PMID- 8003234 TI - [Effect of liuweidihuang decoction on the changes in metal elements inside the internal organs of "yin-deficiency" mice models]. PMID- 8003235 TI - [Studies on anti-inflammatory protein from the extraction of the larva of Parasa sinica Moore]. AB - As a kind of anti-inflammatory protein fractionated and purified from the larva of parasa sinica, CCP (ip) has a significant anti-inflammatory effect on ear odema induced by croton oil in mice. Its ID50 is 1.6mg/kg, but a dose of 2.5mg/kg can also significantly inhibit the rat ankle odema induced by carrageenan and egg white. PMID- 8003236 TI - Four clinical studies comparing the efficacy of flat-trim and multi-level trim commercial toothbrushes. AB - Four independent clinical studies were conducted to compare the short- and long term effectiveness of three commercially available toothbrushes. Two of the four studies compared plaque removal in a single-use, crossover design, and two studies compared plaque and gingivitis reduction efficacy for a long-term, three month use. The Turesky modification of the Quigley-Hein Plaque Index and the modified Gingival Index were used to assess plaque and gingivitis levels, respectively. The two long-term studies directly compared the Oral-B P-35 and Crest Complete toothbrushes, while the two single-use studies compared the Oral-B P-35, Crest Complete and Colgate Precision toothbrushes. In all four studies, there were no significant differences found between any of the toothbrushes. PMID- 8003237 TI - A review of calculus clinical efficacy studies. PMID- 8003238 TI - Laboratory interproximal access efficacy comparison of a rippled bristles toothbrush and a flat manual toothbrush. AB - The Colgate Plus Rippled Bristles toothbrush and the Oral-B 40 toothbrush were compared using a laboratory device designed to stimulate clinical toothbrushing motions and pressures and measure interproximal access efficacy. The toothbrushing time was sixty seconds for each vertical or horizontal toothbrushing sequence and for each of the three brushing weights tested (250, 500 or 750 grams). Interproximal access efficacy was determined by measuring the maximum width of the brushing stroke on pressure-sensitive paper placed around simulated anterior or posterior teeth. Twenty-four toothbrushes of each design were evaluated for each toothbrushing motion, tooth shape and toothbrushing weight. With vertical toothbrushing motions, the Colgate Rippled toothbrush had significantly higher (p < 0.001) interproximal access efficacy means compared to the Oral-B 40 toothbrush, on anterior tooth shapes at the 250 and 500 grams of brushing weights and on posterior tooth shapes at all of the brushing weights tested. Using the horizontal toothbrushing motion on anterior teeth, the interproximal access efficacy for the Colgate Rippled toothbrush was significantly higher (p < 0.05) than the Oral-B 40 toothbrush at 250 and 500 grams of brushing weights. With horizontal toothbrushing across posterior-shaped teeth, interproximal access efficacy values for the Colgate Rippled toothbrush were significantly higher (p < 0.05-0.001) than the Oral-B 40 toothbrush at all of the brushing weights tested. When the various parameters tested were combined for all brushing weights, both brushing motions or both tooth shapes, interproximal access efficacy means for the Colgate Rippled toothbrush were higher (p < 0.05-0.001) than the combined means for the Oral-B toothbrush. When all factors tested were combined, total interproximal access efficacy for the Colgate Rippled toothbrush was significantly superior (p<0.001) to the Oral-B 40 toothbrush. PMID- 8003239 TI - Laboratory evaluations of interproximal access of two differently bristled manual toothbrushes. AB - The Colgate Rippled Bristles toothbrush was compared to the Oral-B 40 toothbrush using a laboratory device which simulates horizontal and vertical brushing movements under pressures of 250, 500 and 750 grams. Interproximal access was determined by measuring the width of the brushing stroke on pressure-sensitive paper surrounding anterior or posterior tooth shapes. The Colgate Rippled toothbrush was consistently superior to the Oral-B 40 toothbrush in accomplishing interproximal access in the laboratory tests performed here. On anterior-shaped teeth, the superiority (p < 0.05-0.01) was evident at all pressures tested, with both horizontal and vertical brushing movements. On posterior tooth shapes the Colgate Rippled toothbrush was superior (p < 0.01) to the Oral-B 40 toothbrush at all brushing weights and with both vertical and horizontal motions. When total interproximal access efficacy means were calculated for all brushing weights, the Colgate Rippled toothbrush was superior (p < 0.05-0.01) to the Oral-B 40 toothbrush on both anterior and posterior tooth shapes in the vertical and horizontal brushing motions. PMID- 8003240 TI - An electron microscopic comparison of bristle end-rounding of three commercial toothbrushes. AB - The results from three separate examinations using SEM photomicrographs and shape factor (SF) measurements show that Oral-B P-35 brushes have a highly significant difference in bristle end-rounding when compared to Colgate Precision and Crest Complete toothbrushes. The proportion of Oral-B P-35 bristles with highly rounded ends was substantially greater than that for Colgate Precision and Crest Complete toothbrushes. Oral-B also had fewer bristles in the very sharp-edged category than both Complete and Precision toothbrushes. Each toothbrush sample in these studies was purchased from geographically dispersed retail outlets throughout the United States. Scanning electron micrographs were made from a representative random sample of bristles, then digitized and evaluated using image analysis software. The comparisons were made on the basis of the number and distribution of bristles having varying degrees of roundness as determined by shape-factor analysis. Previous studies asserted that low shape-factor values indicate sharp bristle edges that are less conducive to good oral hygiene than end-rounded bristles with high SF values. In separate studies, Oral-B P-35 had a significantly higher number of highly end-rounded bristles than did either the Colgate Precision or Crest Complete toothbrushes. The averages for end-roundness fall in the order of Oral-B P-35 > Complete > Precision. Thus we conclude that the potential for harming dental tissues is less for the Oral-B P-35 toothbrush than for either the Colgate Precision or Crest Complete toothbrushes. PMID- 8003241 TI - Task persistence and learning ability in normal and chronic low dose MPTP-treated monkeys. AB - Monkeys exposed to low doses of the dopamine neurotoxin 1-methyl-4-phenyl-1,2,3,6 tetrahydropyridine (MPTP) develop cognitive deficits in the absence of gross motor dysfunction. Attentional deficits and task impersistence are now also described in these animals. The task impersistence correlated with no-response errors (i.e. errors of omission) on a delayed response task and improved with dopamine agonist therapy. In parallel studies, it was observed that there were significant differences in the ability of normal monkeys to learn to perform cognitive tasks. We found that monkeys classified as poor learners had similar deficits in task persistence as did MPTP-exposed monkeys, suggesting a relationship between poor cognitive performance and task impersistence in untreated as well as MPTP-treated monkeys. The possible significance of these results for two clinical disorders, early Parkinson's disease and attention deficit hyperactivity disorder is discussed. Cognitive and behavioral similarities between chronic low dose MPTP-treated monkeys, early Parkinson's disease patients and people with attention deficit hyperactivity disorder may suggest the existence of related pathophysiological mechanisms in these disorders. PMID- 8003243 TI - The spatial distribution of pigeons' target detection. AB - Pigeons were trained to detect briefly-presented targets that appeared on a flatscreen computer display. Pecks were detected by a touchscreen mounted on the display. Those that were directed at the targets produced grain reward whereas pecks at locations in which the target had not appeared did not produce reward. A "behavioral fixation" procedure was used to ensure that the pigeons were facing the display when the target was presented. In general, the probability of detecting a target was highest in the region surrounding the fixation point and decreased as the target appeared more peripherally, both horizontally and vertically. These results show that pigeons' ability to detect targets in a frontal plane is not uniform. PMID- 8003242 TI - The effects of dietary fatty acid composition combined with environmental enrichment on brain and behavior in mice. AB - In this study we investigated the effects of dietary fatty acid (FA) composition combined with postweaning environmental enrichment on brain fatty acid composition and behavior in mice. There were three dietary conditions: a saturated fat group deficient in essential fatty acids, a group deficient in n-3 fatty acids only, and a control group containing both n-3 and n-6 fatty acids in a ratio of 0.27. Animals were fed these diets during pregnancy and lactation and after weaning. Brain fatty acid composition was determined on days 1, 9, 17 and 25 after birth and in adult animals at 3 months. At weaning two females from each litter were assigned randomly to either an enriched or standard environmental condition. After six weeks in these environments they were tested in the Morris water maze and open field. Adult percentages of 22:6n-3 were present in the brain within the first week after birth. These values were reduced by 50% in the n-3 deficient diet and by 80% in the saturated fat diet; adult animals on the saturated fat diet were also severely retarded in growth. Animals fed the saturated fat diet were initially slightly slower in locating the hidden platform in the Morris maze relative to the control group, but this was not apparent in the reversal learning phase; a cued learning task using a visible platform indicated that these effects did not appear to be related to differences in motor or motivational capacities. The n-3 deficient group did not differ from either the saturated fat group or the controls. All dietary groups showed beneficial effects of environmental enrichment in decreasing their latency to locate the hidden platform, and these effects appeared to be partially independent of the increased swimming speed of the enriched animals. Enriched animals in all groups showed less rearing activity in the open field and spent more time stationary; the animals fed saturated fat reared less and travelled shorter distances more slowly. In all cases the effects of diet and environment were additive, thereby providing little support for the hypothesis that dietary fatty acid composition would affect the animals' capacity to benefit from the functional effects of environmental enrichment. PMID- 8003244 TI - Intracranial androgenic activation of male-typical behaviors in house mice: motivation versus performance. AB - Castrated male mice were bilaterally implanted with 27 ga cannulae containing testosterone into either the septum, medial preoptic area (MPO), or corticomedial amygdala. One additional group of castrates received no hormone and another received only systemic testosterone via subcutaneous silastic capsules. All males were subsequently tested for ultrasonic mating vocalizations, urine marking, mounting behavior, aggression and gender preference, all of which are androgen dependent, male-typical behaviors. In general castrates receiving no hormone performed these behaviors at low levels and animals receiving systemic testosterone performed the behaviors at normal male-typical levels. Ultrasonic vocalizations in response to female urine were activated by MPO implants. Urine marking in response to female urine appeared to be partially activated only with MPO implants. Very little mounting or fighting were seen in the brain implanted groups. Gender preference (for females over males) was restored with MPO implants and appeared to be partially activated with septal implants. The seminal vesicles of the castrates receiving brain implants were not significantly different from those receiving no hormone indicating that little or no implanted hormone was exiting the brain into general circulation. The implications of these findings for the neuroanatomy of sexual motivation and performance are discussed. PMID- 8003246 TI - Visual acuity and hemispheric asymmetries in pigeons. AB - Pigeons and domestic chicks tested under monocular conditions in pattern distinction tasks generally show higher discrimination performances with the right eye seeing. At least two different mechanisms could mediate this asymmetry: the dominance of the right eye could either be due to hemispheric differences in the cognitive operations performed during these tasks, or may reflect a lateralization in the spatial frequency discrimination capacity of the left and the right eye system. The aim of the present study was to decide between these two hypotheses. Therefore nine adult homing pigeons (Columba livia) were tested with the left or the right eye seeing in a visual acuity task using high-contrast square wave gratings. Visual acuity, defined as the spatial frequency at which the psychometric function crossed the 75% correct line was virtually identical for the two eyes with 6.6 for the left and 6.4 c/deg for the right eye. Thus, visual lateralization as demonstrated in various pattern discrimination tasks seems not to depend on asymmetries in acuity but probably reflects hemispheric differences in the visual processing mode. PMID- 8003247 TI - Post-stimulation excitability of diencephalic self-stimulation neurons. AB - We used the double-pulse technique with moveable electrodes to estimate the refractory periods of self-stimulation neurons within the rat's dorsal diencephalon and surrounding areas. Refractory period estimates varied substantially depending on the site of stimulation. For some sites, recovery from refractoriness was noted at post-stimulation intervals as short as 0.5 ms, an estimate similar to that reported for the MFB axis and the dorsal raphe and periaqueductal grey. The longest recovery intervals were similar to those reported for the prefrontal cortex, caudate, and substantia nigra. Step-like recovery (believed to indicate the presence of neural populations with non overlapping refractory periods) was also noted in several sites. The large range of recovery intervals found in the present study may suggest that the diencephalon plays an integrative role for rewarding signals arriving from various brain areas. PMID- 8003245 TI - Effect of PKC inhibitors and activators on memory. AB - Changes in the activity of the enzyme protein kinase C (PKC) have been implicated in learning and memory consolidation, and in the induction of long-term potentiation. The precise role of PKC in memory processing is still unknown. Using 1-day-old chicks trained on a single-trial passive avoidance task, we demonstrate that inhibition of PKC activity by melittin induced retention loss, in a dose-dependent manner, in the second stage of a three-stage sequence of memory processing. The effect was lateralized to the left hemisphere of the chick forebrain. This effect of melittin was prevented by high concentrations (16-320 microM) of the PKC activator, phorbol 12-myristate 13-acetate (PMA). Furthermore, concentrations of PMA in the range 1.6 to 40 microM were shown to induce long term memory consolidation following a weakly reinforced version of the learning task, which normally does not lead to formation of long-term memory. That these actions of PMA are attributable to PKC activation is supported by the further finding that the inactive phorbol ester 4 alpha-PDD had no effect either on melittin-induced amnesia or on memory consolidation following weakly reinforced learning. Paradoxically, concentrations of 16 microM or higher of PMA inhibited memory consolidation for the normal strongly reinforced learning trial, an effect again not observed with 40 alpha-PDD. The results are consistent with the view that PKC activity may be implicated in a pre-long-term stage of memory processing. PMID- 8003248 TI - Relationships between septo-hippocampal cholinergic activation and the improvement of long-term retention produced by medial septal electrical stimulation in two inbred strains of mice. AB - This experiment was designed to highlight the relationships between septo hippocampal cholinergic activation and the processing of memory consolidation. For that purpose, we have analyzed the consequences of a medial septal electrical stimulation (100 Hz, 30 microA) applied soon after partial acquisition session of an appetitive operant conditioning task on in vivo hippocampal cholinergic activity on the one hand and on subsequent retention 24 h later on the other hand. For maximize our data base for such comparison we used two neurochemically and behaviorally distincts strains of mice, BALB/c and C57BL/6. In these conditions, our results showed that BALB/c mice evidenced better performance in retention than C57BL/6 mice after medial septal stimulation. On the other hand, the stimulation applied in resting conditions produced a moderate and similar hippocampal cholinergic activation in the two strains. Moreover, in BALB/c mice the only strain which exhibited good consolidation capacities the stimulation do not induced any additive effect on the substantial increase of the hippocampal cholinergic activity produced by the previous acquisition session. Finally, a correlative study realized in C57BL/6 mice seems to indicate that the higher the hippocampal cholinergic activity was the lower were the consolidation capacities. These results lead us to suggest that the improvement of memory consolidation induced by the medial septal stimulation is the consequence of the recruitment of non cholinergic elements located close to the electrode tip. Consequently the septo-hippocampal cholinergic activation is more likely to facilitate certain information processes prior to the consolidation mechanisms proper. PMID- 8003249 TI - Ejaculation induced changes in escape latency in the hot plate test: pharmacological analysis of anxiolytic versus analgesic effect. AB - The possible changes in nociception at various stages of male sexual behaviour were explored in the hot plate test. Although other authors have reported an antinociceptive effect of mating, we failed to find this effect on the hot plate test after several sexual behaviour events. To further explore the possible antinociceptive action of copulation we administered a suboptimal analgesic dose of morphine (0.3 mg/kg i.p.). No change in nociception were observed in animals treated with a subthreshold dose of morphine and tested in the nociception test after ejaculation were observed. Since previous reports have refered that ejaculation produces hypoalgesia when measured in the hot plate test, we attempted to replicate these findings. We found that one ejaculation produces an increase in the latency to escape in male rats previously habituated to the hot plate test. These results suggest a hypoalgesic effect. However, such changes could also be interpreted as alterations in the animals' emotionality. Thus, a group of habituated animals was tested on the switched off plate. An important increase in the escape latency behaviour after ejaculation was observed, while no differences between control animals, without sexual behaviour display, tested on switched on and switched off plate were observed. The participation of the benzodiazepine and opiod systems in the ejaculation effect on the switched off plate was explored. A similar increase in escape latency to that induced by ejaculation was caused by diazepam (1.0 and 2.0 mg/kg). The increase in escape latency induced by ejaculation was prevented by the benzodiazepine antagonist, flumazenil (20.0 mg/kg).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8003250 TI - Differential effects of lesions of the dorsomedial and dorsolateral caudate putamen on reaction time performance in rats. AB - In order to investigate the role of the dorsomedial and dorsolateral caudate putamen (CPu) in movement initiation of rats, we examined the effects of quinolinic acid lesions (30 nmol in 1 microliter) in these striatal subregions in a simple reaction time task. Results show that lesions of the dorsomedial, but not of the dorsolateral CPu increased reaction times. These findings provide further evidence for a functional heterogenity of the CPu and demonstrate an involvement of the dorsomedial CPu in processes related to rapid initiation of responses. PMID- 8003251 TI - New active analogues of Cucurbita maxima trypsin inhibitor III (CMTI-III) modified in the non-contact region. AB - Four new analogues of trypsin inhibitor CMTI-III(3-28) = [desArg1,desVal2,desGly29]CMTI-III which was recently shown to be fully active, were synthesized by the solid-phase method. The introduction of glycine in position 9 (peptide 1) and Gly-Pro-Gly (peptide 2) and Gly-Pro-Asn (peptide 3) in the regions 17-19 and 23-25, respectively, did not change the antitrypsin activity of all modified peptides. All of these substitutions are presumed to be outside the trypsin-binding loop as judged from the X-ray structure of the complex between beta-trypsin and the related inhibitor CMTI-I. Also the fourth analogue which was substituted in all the positions mentioned, exhibited the full activity. PMID- 8003252 TI - Further evidence that human lysosomal sialidase is not derived from prosaposin. Prosaposin biosynthesis and ganglioside sialidase studies in prosaposin- and sialidase-deficient fibroblast lines. AB - Human lysosomal sialidase has been considered by Potier et al. (Potier M., Lamontagne S., Michaud L., Tranchemontagne J. (1990) Biochem Biophys Res Commun 173, 449-456) to be a processing product of prosaposin, the common precursor of the saposin proteins A, B, C, and D that function as activators in the lysosomal degradation of sphingolipids. We tested this hypothesis on cultured fibroblasts of patients with prosaposin deficiency, a neurolipidosis caused by a complete lack of synthesis of the prosaposin protein, by determining their lysosomal and, for comparison, their plasma membrane sialidase activities. Using both the natural substrate ganglioside GM3 and the synthetic compound 4-methylumbelliferyl neuraminate, we found the lysosomal sialidase activity in the prosaposin deficient cells to be in the normal control range; normal values were also found for the plasma membrane sialidase. In fibroblasts from patients with a genetic deficiency of the lysosomal sialidase (sialidosis), on the other hand, biosynthesis and processing of prosaposin were unimpaired. Our findings therefore show no precursor/product relationship between prosaposin and the lysosomal or the plasma membrane sialidase. PMID- 8003253 TI - Evidences for physically different catalytic and regulatory nucleotide binding sites on the chloroplast H(+)-ATPase. AB - Chloroplast thylakoids which were incubated with pyridoxal-5-phosphate (PLP) in the dark, exhibit a slower ADP-binding curve in the light and lack the rapid initial phase of rebinding of loosely bound nucleotides upon de-energetization. The [14C]NBD binding pattern in subunits of PLP-modified thylakoids is reduced to that one found if ADP was present in the modification step. The [14C]NBD binding pattern in subunits of activated and successive PLP-modified CF1 is reduced to that one found in the latent enzyme. As in the latent (not activated) ATPase Lys beta 359 is modified by PLP, we conclude that this amino acid residue belongs to a regulatory binding site which binds ADP tightly upon de-energetization and releases it upon energetization. In the activated enzyme, however, the modified residue is related to a 9 kDa peptide in beta, which contains the conserved lysine 178. This site is proposed to be a catalytic one. PMID- 8003254 TI - Nonlinear dynamic processes in open single enzyme systems. AB - Chemical oscillations are predicted theoretically in single enzyme systems open to substrate containing a regulatory enzyme, which shows a slow substrate activation. The time-evolution of the system is well described by two ordinary differential equations. The conditions for oscillations or overshoot phenomena of the substrate concentration were analysed by numerical simulation. The existence of damped oscillations or overshoot phenomena in a regulatory enzyme reaction, open to substrate, has been proved experimentally in the pyruvate decarboxylase reaction and in the pyruvate dehydrogenase reaction. In both cases the concentration of the substrate pyruvate shows a strongly damped oscillation in a concentration range below the Km-value. PMID- 8003255 TI - Final phase of enzyme reactions following a Michaelis-Menten mechanisms in which the free enzyme and/or the enzyme-substrate complex are unstable. AB - An important kinetic analysis of unstable enzyme systems was carried out by Duggleby (Duggleby, R.G. (1986) J. Theor. Biol. 123, 67-80). This author states that his results are of general validity in the sense that the instability rate constants may have any value. Later, Wang & Tsou (Wang and Tsou (1990) J. Theor. Biol. 142, 531-549) rediscovered Duggleby's results when they analyzed a scheme in which the inactivations were due to a non-complexing irreversible inhibitor, pointing out the need to assume an initial steady-state in the catalytic route of the reaction. In the present contribution we show that there are values of the instability rate constants for which the equations of Duggleby are not applicable. We propose, for these cases, an alternative equation, which relates the final substrate concentration with the initial ones of both the substrate and the enzyme. Based on this, an experimental design for the evaluation of kinetic parameters is suggested. The present work concerns enzyme reactions evolving according to a Michaelis-Menten mechanism, in which the free enzyme and/or the enzyme-substrate complex are unstable. PMID- 8003256 TI - Asymmetry and structural changes in ECF1 examined by cryoelectronmicroscopy. AB - The Escherichia coli ATPase (ECF1) has been studied by cryoelectronmicroscopy and an intrinsic asymmetry of the molecule in the hexagonal projection identified. The three beta subunits could be distinguished. One, which we have called beta 1, has a greater density in projection than the other two; the second, beta 2, is of intermediate density in projection, while the third, beta 3, is smeared out in density. These different features of the beta subunits were used to orient images, and the positions of the gamma and epsilon subunits then established. The location of the gamma subunit, as monitored by the central mass, was not fixed. This subunit could be found in positions that followed an arc from close to beta 2 to close to beta 3, a shift of around 10A, with respect to the center of the mass. The location of the epsilon subunit was monitored after reconstituting a complex of epsilon subunit-depleted ECF1 with a mutant epsilon subunit in which His at residue 38 had been replaced by Cys, and this Cys labeled with an approximately 14A gold particle. The epsilon subunit was found in positions described by an arc between an alpha subunit (alpha 1) and the neighboring beta subunit (beta 1), a shift of around 20A, with respect to the center of the gold particle. A nucleotide dependence of the position of the gamma subunit has been established by Gogol, E.P., Johnston, E., Aggeler, R. and Capaldi, R.A. (1990) Proc. Natl. Acad. Sci. USA 87, 9585-9589. A nucleotide dependence of the position of the epsilon subunit is shown here.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8003258 TI - Dimerization of Bence Jones proteins: linking the rate of transcription from an Escherichia coli promoter to the association constant of REIV. AB - Homodimers of immunoglobulin VL domains are minimal models of antibodies in that they display an ensemble of six hypervariable loops. Bence Jones protein REI is a mixture of a complete kappa light chain and the corresponding variable domain (REIV). The known three-dimensional structure of the REIV dimer (Epp et al., 1975, Biochemistry 14, 4943-4952) provides a basis for studying dimer stabilization by protein engineering. Mutant REIV-L94H was constructed and shown to have an equilibrium constant of dimerization about one order of magnitude higher than wildtype REIV. By fusing REIV and variants to the aminoterminal part of the Vibrio cholerae ToxR regulator protein (Miller et al., 1987, Cell 48, 271 279), a transcriptional signal in E. coli can be derived from REIV homodimer formation constant. The system senses dimerization of the immunoglobulin part of the fusion protein, located in the periplasmatic space, and transduces the signal as transcriptional activation to a ctx::lacZ gene construct integrated into the E. coli chromosome. There is positive correlation between the propensities of homodimer formation and the rate of transcriptional initiation at the ctx promoter. Since beta-galactosidase levels can easily be measured colorimetrically in crude cell lysates of a large number of clones using an ELISA reader, this procedure constitutes all elements required for a genetic screen in E. coli for immunoglobulin variants with altered association constants. PMID- 8003257 TI - Ubiquitin and ubiquitination in cells from the marine sponge Geodia cydonium. AB - Marine sponges, e.g. Geodia cydonium, have been intensively used to investigate the biochemical and molecular biological basis of cell-cell- and cell-matrix adhesion. It has been shown that a family of galactose-specific lectins, which are present in the extracellular space of G. cydonium, is a main component involved in cell-matrix adhesion in the sponge system. In the present study it is outlined that the purified 16-kDa lectin-1 binds to a 67-kDa membrane-associated protein. This lectin-binding protein undergoes mono- and diubiquitination after incubation of dissociated sponge cells with the homologous aggregation factor (AF), a molecule involved in cell-cell adhesion. The gene coding for polyubiquitin was characterized and found to be composed of three tandem repeat building blocks. Northern analysis indicated the presence of only one type of ubiquitin-specific mRNA (1.65 kb). The level of this transcript increased by 10 fold after incubation of the dissociated cells with AF for 8 h; in contrast, lectin-1 caused only a small effect on the steady-state level of ubiquitin mRNA. These data indicate that the expression of the polyubiquitin gene is directly or indirectly regulated by the AF and suggest that ubiquitination might be a process which controls the function of the membrane-associated lectin-binding protein during matrix-cell adhesion. PMID- 8003259 TI - Secondary fungal metabolites and their biological activities, V. Investigations concerning the induction of the biosynthesis of toxic secondary metabolites in basidiomycetes. AB - In cultures of the basidiomycetes Heterobasidion annosum, Gloeophyllum abietinum or Armillaria ostoyae, the biosynthesis of some of their toxic secondary metabolites is enhanced up to 400-fold when they grow in the presence of an antagonist. This stimulation is induced before any cell contact occurs. The "inducing signals" are not macromolecules, polypeptides or constituents of the cell membranes, but the same toxins which are synthesized already in monocultures in very low concentrations. After excretion and diffusion into the media, the fungi thus recognize the proximity of the antagonist in dualcultures. As a consequence, the enormous stimulation of toxin synthesis takes place. The increasing toxin concentrations in the fungal dual cultures finally cause the formation of mycel-free growth inhibition zones between the fungi, or sometimes one of the contrahents is killed. This stimulation of toxin synthesis is achieved by an enhanced de novo synthesis of enzymes of the corresponding secondary pathways. PMID- 8003260 TI - Pass me the blue. PMID- 8003261 TI - The measured intensity of work-related stressors in pediatric oncology nursing. AB - The purpose of this descriptive study was to measure the rated intensity of work related stressors experienced by pediatric oncology nurses and to examine the reliability of a new instrument. The Stressor Scale for Pediatric Oncology Nurses (SSPON), a 50-item visual analogue instrument, was used to measure the intensity of those work-related stressors. A national sample (n = 92) of randomly selected members of the Association of Pediatric Oncology Nurses participated. Although most subjects had 2 or more years of pediatric oncology nursing experience (92%), the majority had greater than 5 years of experience (52%). Median scores on the SSPON indicated that the nurses sampled experienced a moderately high level of work stress. Scale items rated most stressful were "watching a patient suffer and not be able to do anything about it," "when a favorite patient dies," and "making mistakes." Scale items rated least stressful were "when patients die at home rather than here at the hospital with us," "not feeling comfortable with my skills," and "when I can't answer a question about my patient." A comparison of total scale scores, using a t-test for independent samples, indicated that nurses with less than 5 years of pediatric oncology experience (n = 44) did not differ significantly from nurses with greater than 5 years of pediatric oncology experience (n = 48; t = 1.30, P = .199), in relation to intensity of work-related stress. Reliability was estimated using coefficient alpha. The total scale SSPON was found to be internally consistent (coefficient alpha = 0.93).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8003263 TI - Measuring pain in pediatric oncology ICU patients. AB - Thirty patients (ages 5 to 13) hospitalized in a pediatric oncology intensive care unit (ICU) rated the presence and severity of their pain on the Faces Pain Scale (FPS) and the Poker Chip Tool (PCT). Parents independently rated the child's pain on these scales and each patient's nurse completed the Objective Pain Scale (OPS). Patients' ratings on the FPS correlated significantly with parents' ratings on this scale (tau = .48, P = .002) but not on the PCT (tau = .23, P = .16). Nurses' ratings on the OPS were moderately correlated with patients' FPS ratings (tau = .37, P = .02) but were only weakly associated with PCT ratings (tau = .27, P = .09). The majority of patients, parents, and nurses expressed a preference for the FPS over the PCT. The FPS appears to be a clinically useful and accurate approach for measuring the pain of pediatric oncology patients in an ICU but is limited to those who can participate in a self report measurement. PMID- 8003262 TI - Behavioral training of motion control in young children undergoing radiation treatment without sedation. AB - Preschool-age children undergoing radiation treatment for malignancies often require daily sedation or general anesthesia to assure adequate motion control. A few older children with severe anxiety reactions, a history of behavior problems, or developmental handicaps have similar problems with radiotherapy. The use of sedation or anesthesia adds risk and expense to a procedure that does not require their administration for pain management. This report describes an alternative approach using behavior analysis to teach cooperation and motion control to preschoolers and older children with special needs. Outcome data are presented for 10 children between the ages of 3 and 7. Eight of the 10 appeared to benefit from the behavioral program. These eight cooperated with radiation treatments without the need for repeated sedation or anesthesia. The benefits and limitations of this approach are discussed along with the need for additional research. PMID- 8003264 TI - What caused my child's cancer? Parents' responses to an epidemiology study of childhood cancer. AB - When a child is diagnosed with cancer, parents try to understand why the cancer developed. Although usually it is not possible to explain what caused an individual child's cancer, clinical experience has shown that parents do form theories about the origins of their child's illness although, or perhaps because, no one knows the actual cause. A parent-completed epidemiology questionnaire (EQ), designed to provide a comprehensive and general epidemiology data base for studies conducted by the Childrens Cancer Group, included an open-ended item ("Do you have any additional comments or concerns about anything that could have caused or contributed to your child's illness?"). A convenience sample of 500 EQs containing responses to the open-ended question was reviewed independently by two experienced pediatric oncology nurses. Statements contained in the responses were categorized into 12 major themes according to content: concern about environmental exposures (n = 303), concern about family health history (n = 270), specific causality attribution (n = 39), puzzlement (n = 24), concern with cancer "clusters" (n = 23), concern with stress (n = 22), altruism (n = 15), specific feedback requests (n = 11), myths/misconceptions (n = 5), advocation of preventive education/screening (n = 4), active information-seeking (n = 6), and parental self-blame (n = 4). These themes or concerns provide useful information that can be applied in planning educational and supportive clinical interventions, as well as further research. PMID- 8003265 TI - Pentamidine. PMID- 8003266 TI - Bringing childhood cancer information to the community: a "traveling roadshow" for school nurses. PMID- 8003267 TI - X-ray diffraction study of the crystal structure of the pi-molecular compound pyrene ... pyromellitic dianhydride at 19 K. AB - The crystal structure of the pyrene ... pyromellitic dianhydride (PMDA) pi molecular compound [(C16H10:C10H2O6); PYRPMA] has been refined from intensities measured at 19 K using the low-temperature accessory designed by Samson, Goldish & Dick [J. Appl. Cryst. (1980), 13, 425-432] for a four-circle diffractometer. Earlier results for the ordered structure [Herbstein & Snyman (1969). Philos. Trans. R. Soc. London Ser. A, 264, 635-666] are confirmed and extended; at 19 K, a = 13.664 (3), b = 9.281 (2), c = 14.420 (3) A, beta = 91.80 (2) degrees, space group P2(1)/n, Z = 4, with two sets of pyrenes at independent centres of symmetry and the four PMDAs at general positions. The geometrical structures of the two components are in good agreement with quantum mechanical calculations. Analyses of thermal motion and packing show that one set of pyrenes is more tightly packed than the other; the principal interactions in the crystal are pi-pi* plane-to plane interactions between pyrene and PMDA and > CH ... O = C <, between pyrene and PMDA, and between PMDAs. PMID- 8003268 TI - X-ray diffraction study of the disorder-to-order transition at approximately 160 K in the pi-molecular compound pyrene ... pyromellitic dianhydride. AB - The crystal structure of pyrene ... pyromellitic dianhydride [(C16H10:C10H2O6); PYRPMA] has been studied over the range 300-19 K, using the low-temperature accessory designed by Samson, Goldish & Dick [J. Appl. Cryst. (1980), 13, 425 432] for a four-circle diffractometer. Earlier results for the disordered and ordered structures [Herbstein & Snyman (1969). Philos. Trans. R. Soc. London Ser. A, 264, 635-666] are confirmed and extended. At 295 K, a = 13.94 (1), b = 9.34 (1), c = 7.31 (1) A, beta = 93.65 (9) degrees, space group P2(1)/a, Z = 2, with pyrenes and pyromellitic dianhydrides (PMDAs) at crystallographic centres of symmetry. At 19 K, a = 13.664 (3), b = 9.281 (2), c = 14.420 (3) A, beta = 91.80 (2) degrees, space group P2(1)/n, Z = 4, with two sets of pyrenes at independent centres of symmetry and the four PMDAs at general positions. There are no discontinuities in cell dimensions with temperature (measurements at approximately 10 K intervals, down to 19 K) but db/dT and d beta/dT show discontinuities at approximately 167 K. Superlattice reflections appear below approximately 164 K (= Tc by X-ray diffraction), corresponding to the doubling of c and change of space group; the specific heat shows an anomalous increase over the range 120-155 K, giving a lambda-type peak. These results show that the transition is second order with regard to Ehrenfest's criteria. PYRPMA is a co elastic crystal and quantitative analysis shows a linear dependence of the squares of spontaneous strain and of normalized superlattice intensity on temperature; hence, in terms of Landau theory, the transition is tricritical. However, the excess specific heat cannot be explained entirely on this basis. The physical nature of the transition is discussed. PYRPMA is so far unique among the pi-molecular compounds showing disorder-to-order transitions in the solid state in that there is a doubling of one of the axes; all indications are, however, that it resembles the other examples in the sense that subtle intermolecular packing interactions (here between pyrenes and PMDAs) are the driving force for the transition rather than electronic or charge-transfer interactions. PMID- 8003269 TI - X-ray diffraction studies of oriented dilauroyl phosphatidylcholine bilayers in the L delta and L alpha phases. AB - X-ray diffraction studies on oriented multilayers of dilauroyl phosphatidylcholine in the lyotropic liquid-crystalline L alpha phase and a not previously reported mono-domain three-dimensional L delta phase at two temperatures (293 and 343 K) and various relative humidities (0-100%) are described. Absolute one-dimensional electron-density profiles of the different structural phase bilayers were constructed to a resolution of 4 A using direct methods (e.g. swelling and triplet structure-invariant relationships) to solve for the phase problem. The absolute electron-density distributions clearly demonstrate differences between the two structural phases of dilauroyl phosphatidylcholine bilayers. In addition, the various structural properties of the two different phases have been quantified. In the case of the L delta phase, the structural quantities (e.g. volumes of the terminal methyl group and headgroup, and the number of waters) are examined for the first time. PMID- 8003270 TI - Structure of 1,1,5,5-tetranitro-[4]peristylane. Structure solution from molecular packing analysis. AB - The structure of the title compound, decahydro-2,2,5,5-tetranitro-1,6:3,4 dimethanocyclobuta[1,2: 3, 4]dicyclopentene, C12H12N4O8, was solved with the molecular packing program MOLPAK, starting with an AM1-geometry-optimized model of an isolated molecule. The 20 best predicted crystal structures from the MOLPAK procedure were subjected to lattice energy refinement with the WMIN program. A structure-factor calculation with the top MOLPAK/WMIN derived structure and the 197 Fo data to sin theta/lambda = 0.324 A-1 (theta = 30 degrees) gave an R value of 0.29. Final R = 0.057, wR = 0.067 for 730 reflections with I > 3 sigma (I). There are no unusual intermolecular distances and crystal packing is normal. PMID- 8003271 TI - Siesta and ambulatory blood pressure monitoring. Comparability of the afternoon nap and night sleep. AB - A prospective analysis of consecutive ambulatory blood pressure monitorings over a 5 month period identified 50 subjects (35%) who took an afternoon nap during the monitoring. The average duration of daytime sleep, as reported by the patients, was 1.8 +/- 0.6 h compared with the reported 7 +/- 2 h for nighttime sleep. Ambulatory blood pressure values during daytime awake periods were significantly higher compared with daytime sleep and nighttime sleep. The blood pressure decline during daytime sleep and nighttime sleep was similar. The pattern of blood pressure changes during daytime sleep was comparable in normotensive (n = 16), untreated (n = 10), and treated hypertensives (n = 24), irrespective of age, gender, and the level of blood pressure. The marked decline in blood pressure during daytime sleep suggests that sleep itself, rather than an endogenous circadian rhythm, is responsible for the blood pressure dip observed during both daytime sleep and nighttime sleep. Ignoring actual sleeping time in people who sleep during the day may greatly distort the day-night ambulatory blood pressure difference, when the latter is calculated on the basis of arbitrarily defined "day" and "night" periods. PMID- 8003272 TI - Value of ambulatory blood pressure monitoring in type I (insulin-dependent) diabetic patients with incipient diabetic nephropathy. AB - Ambulatory blood pressure monitoring (ABPM) is currently proposed for measuring blood pressure in type I, insulin-dependent diabetic subjects with incipient diabetic nephropathy. However, the value of this method, in comparison with conventional ones in detecting blood pressure differences between normotensive type I, insulin-dependent diabetic subjects with or without microalbuminuria, is questionable. We obtained systolic, diastolic, and mean blood pressures (SBP/DBP/MBP) in 10 hospitalized normotensive type I, insulin-dependent diabetic subjects with microalbuminuria, and in 29 others without, using a mercury sphygmomanometer (method 1) and an automatic device (Dinamap; method 2) to obtain morning (9 to 11 AM) measurements, and ABPM (SpaceLabs 90207; method 3) to obtain daytime (7 AM to 10 PM) and nighttime (10 PM to 7 AM) measurements. During the daytime, SBP/DBP/MBP values were higher in microalbuminuric than in normoalbuminuric patients, whatever the blood pressure measurement method used (P = .034/.061/.033, two-factor ANOVA). Analysis of 24-h ABPM also showed higher SBP/DBP/MBP in microalbuminuric than in normoalbuminuric patients (P = .022/.040/.016), and demonstrated a defect in nocturnal SBP decrease in microalbuminuric compared with normoalbuminuric patients (P = .028). Stepwise multiple regression analysis indicated nocturnal SBP as the only independent factor determining for microalbuminuria (F = 6.72). Thus ABPM, in relation to other methods, indicates above all that the most relevant blood pressure change in type I insulin-dependent diabetic subjects with microalbuminuria is a defect in nocturnal SBP decrease. PMID- 8003273 TI - Assessment of arterial distensibility by monitoring the timing of Korotkoff sounds. AB - The timing of Korotkoff sounds, blood pressure, and heart rate can now be monitored in the ambulatory patient: the QKD interval is the time between the onset of the depolarization on the electrocardiogram (Q) and detection of the last Korotkoff sound (K) at the level of brachial artery during cuff deflation, corresponding to diastolic blood pressure (D). Because this interval is inversely related to pulse wave velocity, this recently developed device enables evaluation of the influence of blood pressure on arterial rigidity, providing valuable information on the properties of the arteries. In this study, we examined the influence of hypertension and age on the above parameters and their correlations to left ventricular mass. QKD interval, blood pressure, and heart rate were monitored over a period of 24 h (four measurements/hour) in 33 normotensive and 70 untreated essential hypertensive patients. The slopes of the plots of QKD interval versus systolic and pulse pressure during the 24 h were calculated for each patient. The influence of age and hypertension on these slopes was tested by comparison of matched groups and multivariate analysis. Moreover the relationships between these parameters and echocardiographically assessed left ventricular mass were studied in 37 patients. We found a reduction in mean QKD interval with age and hypertension, reflecting the recognized higher pulse wave velocity in these patients. The slopes of the plots of QKD interval versus blood pressure were also lower in these patients, indicating the smaller influence of a change in blood pressure on pulse wave velocity in patients with stiffer arteries.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8003274 TI - Exercise blood pressure response and 5-year risk of elevated blood pressure in a cohort of young adults: the CARDIA study. AB - Systolic blood pressure response to exercise has been shown to predict development of hypertension in men, but this association has not been examined in population-based samples of men, or in women or non-whites. This relationship was explored in 3741 normotensive black and white young adults undergoing treadmill testing in the CARDIA study and examined 5 years later for development of hypertension. Exaggerated response to exercise (systolic pressure > or = 210 mm Hg in men and > or = 190 mm Hg in women) was detected in 687 subjects (18%) at baseline, and incident hypertension (blood pressure > or = 140/90 mm Hg or on medication) was detected in 184 subjects (4.9%) at followup. Persons with exaggerated response to exercise at baseline had 5 mm Hg higher systolic and 1 mm Hg higher diastolic pressures at follow-up (P < .005) and were 1.70 times more likely to have developed hypertension than were persons with normal response (P < .001). After adjustment for age, race, sex, clinic, resting systolic pressure, body mass index, heavy activity score, exercise duration, and preexercise systolic pressure, exaggerated response was associated with a 2.14 mm Hg increase in year 5 systolic pressure (P < .0001). These associations did not differ by race or sex. Although the increment in systolic pressure associated with exaggerated exercise response was small (1 to 3 mm Hg), this small increment sustained over time could lead to a substantially increased incidence of hypertension and hypertension-related target organ damage. Determination of factors associated with exaggerated response may provide further insights into the development of hypertension in young adults.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8003275 TI - Anthropometric measures, fitness and habitual physical activity in offspring of hypertensive parents. Dutch Hypertension and Offspring Study. AB - As part of the Dutch Hypertension and Offspring Study, subjects with contrasting risk for hypertension according to their parental history of hypertension were compared with respect to anthropometric measures and measures of fitness and physical activity. Body height, weight, two skinfolds, and blood pressure at rest were measured. Fitness was evaluated by a maximal exercise test, and habitual physical activity was assessed using a questionnaire. No differences were observed in body mass index after adjustment for slight differences in age and proportion of men between the groups (difference between groups: 0.74 kg/m2, 95% CI: -0.30, 1.78). Offspring of hypertensive parents, however, had significantly more central fat (difference between groups: 2.32 mm, 95% CI: 0.18, 4.46). No differences in fitness or physical activity were present between the two groups. The results of this study indicate a potential role for central fat in the etiology of primary hypertension. Fitness or habitual physical activity are, however, not different between groups of subjects at different risk for future hypertension. PMID- 8003276 TI - Drinking pattern and blood pressure. AB - Large amounts of alcohol are known to increase blood pressure. There is little evidence about the effect of binge drinking of alcohol on blood pressure, although this is the dominant style of alcohol drinking in several countries. The purpose of the present study was to examine the relationship between binge drinking and blood pressure using daily heavy drinkers as a reference group. We examined 260 consecutive nonalcoholic 40- and 45-year-old men participating in a health screening. There were 37 teetotalers, 147 social drinkers, 62 weekend heavy drinkers attending the health screening 2 to 7 days after binge drinking, and 14 men who drank heavily every day. Group division was made using self reported alcohol consumption and a structured alcohol questionnaire. Blood pressure was measured manually by a mercury manometer. BMDP statistical software was used in the statistical analysis of the material. The diastolic blood pressure of weekend heavy drinkers (mean intake during the weekend, 289 g) did not differ from that found in teetotalers but systolic blood pressure was slightly higher (5 mm Hg, P = .04). In contrast, daily heavy drinkers (mean intake during the weekend [Friday to Saturday], 151 g) had significantly higher systolic (8 mm Hg, P = .04) and diastolic (6 mm Hg, P = .05) blood pressure values than teetotalers. We conclude that different drinking habits seem to have different effects on blood pressure, those of daily heavy drinking being more prominent than those of weekend heavy drinking. PMID- 8003277 TI - Accuracy and performance of the Terumo ES-H51, a new portable blood pressure monitor. AB - A high performance portable automatic sphygmomanometer, the Terumo ES-H51 (104 g, 58 x 22 x 92 mm), was newly developed for clinical use as a substitute for auscultation using a mercury sphygmomanometer. This device usually displays blood pressure (BP) values obtained by the Korotkoff sound method (K-method). However, when the device judges that BP values obtained by the K-method are inaccurate or unreliable, it substitutes automatically BP values obtained by the cuffoscillometric method (O-method). The accuracy and reliability of the device was tested by comparing it to the auscultation with the standard mercury sphygmomanometer. The mean difference between BP values obtained by the standard method and those obtained by the K-method were -0.7 +/- 2.9 mm Hg systole (mean +/- SD) and -0.3 +/- 2.6 mm Hg diastole, whereas the difference between the former and those obtained by the O-method were 0.3 +/- 5.7 mm Hg systole and 0.3 +/- 4.3 mm Hg diastole (n = 170). The agreement between the BP values obtained according to each of the two methods using the device and the standard method was within 5 mm Hg for 72% to 93% of both systolic and diastolic readings. Therefore, BP values measured by the ES-H51 are accurate. The ES-H51 is sufficiently small and light to be carried easily anywhere. The objective and reproducible BP information obtained by the present device would be useful in clinical practice. PMID- 8003278 TI - Basal and thrombin-stimulated platelet cell calcium. AB - To study platelet cell calcium in dogs, we measured the fura-2-determined calcium concentration (Cai) in platelets derived from blood drawn through indwelling arterial catheters in four dogs. Platelet samples were obtained 3 days a week for 39 days. Canine platelet Cai averages 40.5 +/- 1.7 nmol/L when corrected for extracellular fura-2 dye (n = 46); this mean is significantly smaller than the value obtained without such a correction (50.2 +/- 2.0 nmol/L, P < .05). The amplitude of thrombin-induced Ca2+ transients is proportional to basal Cai, increasing 4.9 +/- 0.9 nmol/L peak Ca2+ per nmol/L increase in baseline Ca2+. PMID- 8003279 TI - Autopotentiation of pressor responses by subpressor angiotensin II in rats. AB - The mechanisms whereby the continuous administration of initially subpressor doses of angiotensin II (ANG II) leads to pressor hyperresponsiveness and gradual development of hypertension were investigated. Male Sprague-Dawley rats (350 to 400 g) were given ANG II intraperitoneally, 200 ng/kg/min, for 24 h, 7 to 10 days, or 6 weeks. Vehicle-infused rats were controls. Pressor responses to incremental doses of ANG II, norepinephrine (NE), and serotonin were measured in chloralose-anesthetized rats, before and after neurohumoral blockade, and the main findings were confirmed in awake, free-moving rats with implanted catheters. Pressure responses to ANG II and NE were also measured in the isolated, pump perfused mesenteric circulation of rats after 7 to 10 days of ANG II or sham infusion. Compared with control rats, there were no hemodynamic changes in ANG II treated rats at 24 h. After 7 to 10 days of ANG II treatment, tail systolic blood pressure rose by 13 mm Hg (P < .01) and pressor responses to ANG II (P < .01) but not to NE or serotonin were increased. Pressor hyperresponsiveness was due in part to potentiation of vascular responses because pressure responses to ANG II (P < .002) but not to NE were also increased in the mesenteric circulation of ANG II-treated rats. By 6 weeks, mild hypertension was well established in ANG II treated rats and pressor responses were increased to both ANG II (P < .05) and NE (P < .01).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8003280 TI - Platelet and erythrocyte membrane microviscosity in Lyon hypertensive rats. AB - The altered membrane microviscosity demonstrated in various cells of spontaneously hypertensive rats (SHR) and essential hypertensive (EH) patients has been proposed to play an important role in the pathogenesis of genetic forms of hypertension. The aim of this study was to evaluate possible changes of membrane microviscosity in platelets and red cell ghosts of Lyon hypertensive (LH) and normotensive (LN) rats. Both erythrocyte and platelet membranes of LH rats had a clear tendency to reduced DPH fluorescence anisotropy reflecting the decreased core membrane microviscosity. On the other hand, there were no changes in TMA-DPH fluorescence anisotropy that characterizes the dynamic properties of the outer membrane leaflet. DPH, but not TMA-DPH, anisotropy correlated negatively with blood pressure. This was true for both red cell ghosts and platelets. Membrane microviscosity had no significant relationship to plasma cholesterol or triglycerides. In platelets, TMA-DPH anisotropy correlated positively with cytosolic free calcium concentration ([Ca2+]i). A similar trend was observed in erythrocytes. In contrast, DPH anisotropy had an inverse relationship to platelet [Ca2+]i. It can be concluded that the alterations of membrane microviscosity seen in LH rats are completely different from those reported in SHR animals and that surface and core membrane microviscosity differ in their relationship to blood pressure and [Ca2+]i. PMID- 8003281 TI - Ambulatory blood pressure and renal function in healthy children and adolescents. AB - Our previous studies using noninvasive ambulatory blood pressure (ABP) monitoring demonstrated racial differences in the diurnal pattern of blood pressure (BP), with higher nighttime BP for African-Americans than for Anglo-Americans despite similar daytime BP. We have hypothesized that the increased BP load in African Americans contributes to the increased prevalence of hypertension and BP-induced target organ damage in adults. The purpose of this study was to examine the relationship between ABP patterns and renal function in healthy, normotensive black and white youths. The subjects were 22 African-American and 28 Anglo American children and adolescents aged 10 to 18 years. Renal function was estimated by creatinine clearance (CCr). The African-American and Anglo-American subjects were similar in age, gender composition, casual BP, and CCr. The relationship between CCr and BP was not significant for casual BP or daytime BP for either group, or with nighttime BP in the Anglo-American subjects. In contrast, CCr was related negatively to both nighttime systolic BP (r = -0.47, beta = -1.21; P < .02) and nighttime diastolic BP in the African-American subjects (r = -0.45, beta = -2.13; P < .03). These results are consistent with our hypothesis. PMID- 8003282 TI - Quality-of-life assessment in treatment of hypertension. PMID- 8003283 TI - On the JNC V report. A different point of view. PMID- 8003284 TI - Synthesis and antimicrobial evaluation of new derivatives of diphenylsulfone. AB - New derivatives of diphenylsulfone have been synthesized and their antibacterial and antifungal activities evaluated. Their chemical structures have been established by means of analytical and NMR spectroscopic data. PMID- 8003285 TI - Synthesis and anticonvulsant activity of new 1-substituted 1'-methyl-3-chloro-2 oxospiro (azetidin-3',4-indol-2' ones). AB - The aim of the present research work is to discover new compounds with potential anticonvulsant activity. Several indolinone derivatives and also azetidinones are reported to have significantly anticonvulsant activity. So, it was thought considerable to synthesise compounds having both these moieties and study their anticonvulsant activity. The new spiroazetinones synthesized from the reaction of 3-(N-substituted) imino-1-methyl-indol-2-ones with chloroacetyl chloride in presence of triethylamine have been characterised on the basis of triethylamine have been characterised on the basis of satisfactory analytical and spectral data. Of the eight compounds screened in the series two compounds (3c and 3h) exhibited significant activity against MES. PMID- 8003286 TI - Oncosuppressor genes: mechanisms of inactivation for the retinoblastoma gene and p53. AB - Mutations that affect oncosuppressor genes contribute to transformed phenotype. The recessive characteristics of these genes require mutations on both alleles. For this reason alterations of the oncosuppressor genes can be transmitted with the germ line. In this review we focus on mechanisms of inactivation of the retinoblastoma gene and p53. The products of these genes are nuclear phosphoproteins involved in controlling cellular proliferation. Inactivated Rb genes have been found in several tumor types. The phosphorylation of the Rb gene product, p105Rb, is regulated by cyclin-dependent kinases in accordance with the cell cycle. Hypophosphorylated wild-type p105Rb is tightly bound to the nuclear matrix and seems to be critical in inhibition of cellular proliferation. Hyperphosphorylation is a physiological mechanism of inactivation of p105Rb. The p53 gene product is a transcriptional factor that blocks the progression of cell division. Mutations in the p53 gene are frequently found in many human cancers and are localized in the highly conserved region of the gene. The protein product of the mutated gene looses its function as a negative regulator of cellular proliferation. The wild-type protein can also be inactivated by forming stable complex with a mutated p53 protein or with the SV large T antigen. PMID- 8003287 TI - Proliferative response of human marginal gingiva to phlogistic process and titanium implant. AB - In order to detect proliferative processes in human marginal gingiva in pathological conditions and after externalization of titanium implants, we have attempted BrdU incorporation after "in vitro" incubation of tissue fragments. In comparison with healthy controls, immunocytochemical detection of samples from patients affected by hypertrophic gengivitis shows a good number of proliferating cells in the basal layer of the epithelium, while only in one case can positiveness be detected after externalization of titanium implants. Since after reduction of inflammation by hygienic treatment a low number of proliferating cells can be observed only in the regions where pathological alterations are also present, we suggest that the increase in tissue proliferation may be closely dependent on the intensity of the inflammatory process. All these data demonstrate that in vitro BrdU incubation of tissue fragments represents a suitable method to evaluate cell proliferation in human tissue. PMID- 8003288 TI - Nucleolar organizer regions activity in lymphocytes of patients with laryngeal carcinoma. AB - The activity of nucleolar organizer regions (Ag-NORs) and the frequency of NOR associations in chromosomes of phytohemagglutinin-stimulated lymphocytes from 12 patients with laryngeal carcinoma and 12 healthy subjects were studied using the gelatine silver staining technique. This study was undertaken to examine whether any disease associated changes occur in NOR activity. A lower mean number of Ag NORs per metaphase (t test, 0.05 > p > 0.02) was found in patients compared to controls. This difference was not due to any specific group of acrocentric chromosomes (D or G). The mean number of NOR associations per metaphase was also found to be markedly lower (t test, 0.01 > p > 0.001) in patients than in controls. This difference was principally due to the significant decrease in the associations between 2 chromosomes (t test, 0.02 > p > 0.01), and in particular to the decrease in the D-G type associations (t test, 0.05 > p > 0.02). These findings are discussed in relation to existing data on the nucleolar activity of lymphocytes in a variety of solid tumours and leukemias. PMID- 8003289 TI - Effect of a peptide fraction extracted from mitochondrial DNA on rat liver cell viability. AB - The authors verified the effect of a peptidic fraction from mitochondrial DNA on liver cell cultures. Primary cultures treated with the mitochondrial peptidic fraction (final concentration 0.025 O.D./ml) showed a higher viability after 48 hours with respect to cultures without mitochondrial peptidic fraction (p < 0.05). The results indicate a probable action of the mitochondrial peptidic fraction on liver cell viability. PMID- 8003290 TI - Effect of a low molecular weight peptide bound to liver mitochondrial DNA on in vitro DNA duplication. AB - Authors tested "in vitro" action of a low molecular weight peptide fraction extracted by mitochondrial DNA from calf liver. The fraction acts upon duplication performed by E. Coli DNA polymerase I on poli dAT dAT template inhibiting chain elongation. The authors hypothesize that a similar role is exerted by this fraction "in vitro" on mitochondrial DNA template. PMID- 8003291 TI - Masseter muscle responses to forelimb nerve stimulation in the guinea pig. AB - These experiments were aimed at clarifying the spinal-masseteric connections by observing the effect of electrical stimulation of radial nerve afferents on masseter muscle activity. Spontaneous and evoked electrical responses of the masseter motor units were recorded with tungsten microelectrodes and analysed on computer. Results show that electrical stimulation of both radial nerves induces responses in single masseter motor units. The response patterns were characterized most frequently by excitation, but also by a sequence of excitation inhibition. The latency in masseter muscle responses were found to be lower in contralateral recordings: 18.26 +/- 4.04 msec (x +/- SD) compared with a latency of 24.3 +/- 5.25 msec in ipsilateral recordings. These observations confirm the hypothesis that somatosensory impulses eminating from the radial nerve participate in the postural control of the masseter muscle aimed at maintaining correct jaw position during forelimb displacement. PMID- 8003292 TI - Bromodeoxyuridine incorporation in corneal epithelium: an immunocytochemical study in rats. AB - Here we investigate the kinetics of rat corneal epithelium at both single cell and tissue level by means of a BrdU-anti BrdU method. The results obtained have then been compared with those previously obtained by us in rat vocal cord epithelium. In this way two main aspects of BrdU incorporation can be indicated at both light and electron microscopy level. First, we report evidence of a new incorporation pattern corresponding to middle S phase, which is characterized by labelling distribution at the border between interchromatin and heterochromatin at ultrastructural level. Second, by comparing tissue incorporation in rats treated with BrdU at the beginning of light time and at the beginning of dark time, we show an increase of cell proliferation during the last hours of dark time and the first hours of light time. In this way, we demonstrate a different progression of circadian rhythms in peripheral regions of corneal epithelium in comparison with that previously observed in vocal cord epithelium. PMID- 8003293 TI - Dermatophilosis in sheep: first report in Italy, experimental reproduction and evaluation of immune response. AB - A severe exudative-crustous and proliferous dermatitis in a 2 year old sheep caused by Dermatophilus congolensis (observed for the first time in Italy), is reported. The disease was reproduced experimentally in sheep, goats, rabbits and guinea pigs, whose skin was treated in different ways before infection. E.L.I.S.A. and Immunoblotting tests carried out in experimentally infected sheep, showed the antigenic complexity of the pathogen and the existence of cross immunity to the protein components. Intradermoreaction tests were carried out in all animals. The development of a positive reaction only in rabbits and guinea pigs, confirmed that these animals have a cellular immunity against Dermatophilus congolensis. PMID- 8003294 TI - In vitro effects of histamine on human pregnant myometrium contractility. AB - The effects of histamine on pregnant human myometrium was examined by means of an in vitro technique. Samples of myometrium were taken from women delivered by elective caesarean section at various stages of gestation. Histamine (1 x 10(-6) to 1 x 10(-4) M) had good stimulant activity on all the strips examined. This contractile action was unaffected by H2 blockers but was competitively antagonised by H1-blockers. The H2-selective agonist, impromidine, was ineffective at molar concentrations between 1 x 10(-8) and 1 x 10(-3) while a specific full agonist of the H1 receptors, thiazole in the range of molar concentrations from 1 x 10(-6) to 3 x 10(-4), had an activity identical to that of histamine. The data obtained suggest that in the pregnant human myometrium the activation of H1-receptors is responsible for the contractile effect of histamine; a possible involvement of histamine in the pathophysiology of labour is discussed. PMID- 8003295 TI - Morphological analysis on the adrenal zona fasciculata of Ginseng, Ginsenoside Rb1 and Ginsenoside Rg1 treated mice. AB - Morphological analysis was performed on the adrenal cortex of depressed mice which received repeated administrations of Ginseng extract or Ginsenoside Rb1 or Ginsenoside Rg1 in order to follow the behaviour of the gland. The left gland was fixed for usual stains and cell measurements of both treated and control adrenal cortex were made on twenty central sections. The outlines of cells from the zona fasciculata, in which nucleus was evident, were traced at 625X using a drawing tube. Cell areas were computed from these drawings by means of image analysis (Optilab software). Our results show that: 1) Ginseng extract administration produces a significant increase in the zona fasciculata cell size with respect to controls. The distribution of soma sizes is generally to the right of the spectrum showing a considerable decrease in cells of small size and a similar increase in cells of intermediate and large size with respect to controls; 2) in Ginsenoside-administered animals, although the mean cell areas is not significantly altered, the distribution of cell sizes shows significant differences between normal and treated animals. It is commonly recognized that mean cell area is in strict connection with cell activity: therefore Ginseng extract may be thought to stimulate adrenal cell activity while the two Ginsenosides have an effect which do not lead to significant changes in mean cell size. PMID- 8003296 TI - UCR disclosure ruling goes into effect! PMID- 8003297 TI - The G.L. Brown Prize Lecture. The cellular machinery of the cochlea. PMID- 8003298 TI - Secretion of acid, gastrin, and cobalamin-binding proteins by the fetal pig stomach: developmental regulation by cortisol. AB - The role of cortisol in the development of gastric function was investigated in the fetal pig. Pregnant sows (term = 114 +/- 2 days, n = 10) were anaesthetized (pentobarbitone) and osmotic minipumps containing either saline or cortisol inserted subcutaneously into fetuses at 82-84 (n = 11) or 91-96 (n = 14) days gestation. Six days later the infused pigs were removed by Caesarean section and the stomach and its contents collected for analysis. Samples were also obtained from unoperated (control) fetal pigs (n = 51) removed under anaesthesia at intervals from 70 days gestation until term. The concentrations of acid in gastric fluid, gastrin in plasma and antral tissue (bioactive as well as precursor forms), and cobalamin(CBL)-binding proteins in fundic tissue were low in control pigs until 100 days gestation. During the last 2 weeks before term, large increases occurred in gastric fluid acidity (from pH 6-7 to pH 3 at birth), plasma amidated gastrin (from 10 to 90 pM) and CBL-binding protein concentration (from 10 to 80 pmol (g fundus)-1). These changes occurred in parallel with a surge in plasma cortisol (from 20 to 200 ng ml-1). Immature fetuses infused with cortisol had significantly higher gastric acidity, plasma amidated gastrin, and concentration of CBL-binding proteins than the corresponding control fetuses (P < 0.05). Across age and treatment groups, significant correlations were found between log10 plasma cortisol values and the above parameters (r = 0.59-0.76, P < 0.01). The results suggest that endogenous cortisol secretion stimulates the secretion of gastric acid, gastrin and CBL-binding proteins in the prenatal period of the pig. PMID- 8003299 TI - Role of fetal sac fluids during maternal water deprivation in sheep. AB - Our aim was to determine the importance of amniotic and allantoic fluids for the maintenance of fetal plasma composition during maternal dehydration when water transfer from mother to fetus is likely to be reduced. Eight pregnant ewes were studied before, during and after water deprivation (36 h), firstly with the fetal fluid sacs intact and then with them drained of fluid for 5 days. When water deprivation was combined with drainage, the increases in the osmolalities, [Na+] and [Cl-] in maternal plasma, in fetal plasma and in lung liquid; the increases in fetal urinary osmolality and [Na+]; and the increases in maternal plasma and fetal plasma arginine vasopressin concentrations were greater than those resulting from water deprivation alone. Our results show that during maternal water deprivation, an absence of fluid in the fetal sacs increases both the osmotic stimulus to the fetus and the fetal responses resulting in conservation of water and salt. We conclude that, when the mother is deprived of water, fluid in the fetal sacs is used to limit the degree of maternal and fetal dehydration. PMID- 8003300 TI - The effect of chronic sodium depletion on renal function in conscious rats. AB - In order to investigate the effect of chronic sodium depletion on renal proximal tubular reabsorption, studies were performed in conscious, unrestrained Brattleboro rats. Since these animals lack circulating vasopressin, fractional water reabsorption in the distal nephron can be assumed to be constant and changes in urine flow rate should therefore reflect changes in end-proximal fluid delivery. Sodium depletion was induced by placing rats on a low-sodium diet (4 mmol Na (kg dry wt)-1) and administering frusemide (40 mg (kg body wt)-1) by gavage on the first 2 days. Extracellular volume, measured after 7-9 days, was reduced by 19% (P < 0.02) as compared with that of rats maintained on a control diet. Urine flow rate, measured during days 4-7 of the low-sodium diet, was significantly lower than that of control rats (142 +/- 8 vs. 168 +/- 5 ml day-1, P < 0.01). Since renal papillary interstitial fluid osmolality was found to be reduced in the sodium-depleted rats (693 +/- 38 vs. 812 +/- 36 mosmol (kg H2O)-1, P < 0.05), it is unlikely that water reabsorption from sites beyond the proximal tubule had increased. The observed reduction in urine flow rate therefore strongly suggests a reduction in end-proximal fluid delivery. In the second part of the study, a single group of Brattleboro rats was used, in which osmotic minipumps were implanted in the peritoneal cavity for continuous infusion of [14C]inulin. After recovery from the operation, the rats were maintained on a control diet for 6 days (pre-control period), then subjected to sodium depletion (low-sodium diet for 6 days, frusemide administration on the first 2 days), and finally returned to the control diet for 6 days, with access to 0.46 M NaCl solution on the first 2 days, in order to restore sodium balance (post-control period). On the final 2 days of each phase, urine flow rate and [14C]inulin clearance (= glomerular filtration rate, GFR) were measured. Urine flow rates during the pre-control, sodium depletion and post-control periods were 169 +/- 7, 132 +/- 8 (P < 0.001) and 176 +/- 8 microliters min-1, respectively; corresponding values for fractional water excretion were 7.0 +/- 0.3, 6.0 +/- 0.5 (P < 0.01) and 7.4 +/- 0.4%. Only a small reduction GFR, of borderline statistical significance, was observed during sodium depletion.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8003301 TI - The effect of high phosphorus intake on calcium and phosphorus retention and bone turnover in growing lambs. AB - Growing lambs were fed diets that just met their requirement for Ca but which supplied either 1 or 3 times their requirement for P and the effects on Ca and P retention and on bone turnover were monitored. Feeding the high P diet had no adverse effect on Ca and P absorption or retention or on bone formation rate. Bone resorption rate was a little higher in lambs fed the high P diet but there were no differences between treatments in plasma parathyroid hormone, 1,25 dihydroxyvitamin D3 or 25-hydroxyvitamin D3 levels or in bone mineral content. It would appear from these results that feeding diets that are rich in P is unlikely to have any adverse effect on skeletal mineralization in the lamb provided that their minimum requirement for Ca is met. PMID- 8003302 TI - Effects of low phosphate intake on bone and mineral metabolism and microbial protein synthesis in lambs. AB - Growing lambs were fed diets either low or adequate in phosphorus and their effects on Ca and P retention, bone formation and resorption and on ruminal microbial protein synthesis were measured. Plasma osteocalcin was used as an indicator of bone formation rate. Levels in plasma were lower in lambs fed the low P diet and were associated with a fall in plasma P concentration and reduced Ca and P retention. Low P intake had no effect on microbial protein synthesis or on bone resorption determined using urinary pyridinoline and deoxypyridinoline as markers. These results suggest that lack of mineral, rather than reduced ruminal microbial protein synthesis, is the main factor contributing to the reduction in bone formation rate seen in lambs fed low P diets. PMID- 8003303 TI - Differential effects of lipid and carbohydrate on enterocyte lactase activity in newborn piglets. AB - The influence of enteral feeding in the neonate on lactase-phlorizin hydrolase activity in the small intestine has been determined in newborn piglets fed a series of modified colostra, with a controlled metabolizable energy intake, during the first 31.5 h of life. Striking differences were observed between lactase specific activity in mucosal homogenates and enterocyte lactase activity along the villus axis; compared with newborns, the former decreased after feeding colostrum, whereas the latter increased significantly. When lipid was present in adequate amount, the increase in enterocyte lactase activity occurred when carbohydrate was present as either lactose or galactose. However, when the lipid content of the diet was low, there was a specific effect of carbohydrate composition which was dependent on position along the villus axis: in the lower villus, colostra high in lactose or glucose stimulated an increase in lactase, but there was no such effect with a high galactose intake. It is concluded that colostrum increases enterocyte lactase activity during the first day of life, and that this is dependent on both the nutrient composition of the diet and the position of the enterocytes along the villus. PMID- 8003304 TI - The role of cyclic AMP in the control of sugar transport across the brush-border and basolateral membranes of rat jejunal enterocytes. AB - Although the involvement of the adenylate cyclase system with glucose transport in the small intestine is poorly understood, there is increasing evidence that cyclic AMP stimulates sugar uptake. In order to study further the effects of cyclic AMP on this process, we have measured glucose accumulation by brush-border and basolateral membrane vesicles prepared from villus enterocytes following exposure of these cells to cyclic AMP and theophylline. Brush-border vesicles derived from enterocytes incubated with cyclic AMP and theophylline accumulated significantly more glucose over a wide range of sugar concentrations, suggesting a change in maximum velocity of the transport system. Glucose uptake by basolateral vesicles was increased at low, but not at high sugar concentrations. Incubation of isolated enterocytes with pancreatic glucagon at concentrations known to stimulate sugar transport by these cells significantly increased enterocyte levels of cyclic AMP. Treatment with glucagon or cyclic AMP resulted in significant hyperpolarization of the potential difference across the brush border membrane, an important driving force for Na(+)-sugar cotransport. The response to glucagon and cyclic AMP appears to be caused by a decrease in Na+ permeability of the mucosal membrane. Taken together, these results suggest that cyclic AMP is a mediator of the actions of glucagon on enterocytes and provide further evidence for a role of cyclic AMP in the modulation of sugar transport across the intestinal enterocyte. PMID- 8003305 TI - Carrier-mediated transport is involved in mucosal succinate uptake by rat large intestine. AB - Mucosal uptake of succinate across the luminal epithelial border in various segments of the large intestine of the rat (proximal and distal colon, caecum) was investigated using an in vitro mucosal uptake technique. For comparison, some experiments with jejunal preparations were also performed. Additionally, disappearance of succinate from the lumen of ligated loops of the proximal and distal colon was measured in vivo. In the ligated loop experiments, the succinate concentration of the instilled solution significantly decreased during a period of 30 min in both colonic segments, indicating absorption of succinate. The in vitro experiments revealed a distinct Na+ dependence of mucosal succinate uptake in all intestinal segments investigated. Because succinate uptake by the colonic mucosa of germ-free rats was similarly enhanced in the presence of Na+ compared with Na(+)-free conditions, measured uptake appears to be due to mucosal uptake rather than to Na(+)-dependent uptake of succinate by bacteria associated with the mucosa. The evaluation of the kinetics of succinate transport in the proximal colon and jejunum, respectively, revealed a single, Na(+)-dependent saturable component and a diffusive component in both intestinal segments. With respect to the apparent kinetic parameters of the carrier-mediated transport component, the transport capacity (Vmax) of the jejunal carrier appears to be substantially higher compared with the colonic mechanism (80 and 11 nmol cm-2 (5 min)-1, respectively) whereas the affinity constants (Km) did not differ markedly in both segments (0.67 and 0.41 mmol l-1, respectively). Mucosal uptake of 14C-labelled succinate in the proximal colon was inhibited by unlabelled succinate, fumarate, citrate and tricarballylate, but not by glutamate, L-leucine or butyrate. Na(+) dependent uptake of the tricarboxylate tricarballylate but not of the dicarboxylate succinate was significantly enhanced by lowering the pH from 7.0 to 5.5, indicating preferential transport of the protonated forms of tricarboxylates. It is concluded from the present results that a Na(+)-dependent, saturable carrier is involved in the uptake of structurally related tri- and dicarboxylates by the colonic mucosa of the rat. PMID- 8003307 TI - Rectangular hyperbola fitted to muscle force-velocity data using three dimensional regression analysis. AB - A simple method is described for fitting a rectangular hyperbola to force velocity data derived from active muscle. The approach is based on three dimensional regression analysis of the variables force, velocity and (force x velocity). The usage of the method is illustrated by practical applications. A pocket calculator is sufficient for the mathematical treatment. PMID- 8003306 TI - Effects of low intensity infrared laser irradiation upon conduction in the human median nerve in vivo. AB - The current investigation, for which ethical permission was obtained, was designed to assess the putative neurophysiological effects of low intensity (9.6 J/cm2) laser (830 nm) irradiation upon conduction latencies in the human median nerve in vivo. Antidromic nerve conduction studies were performed on the non dominant arms of healthy human volunteers (n = 51), who were each assigned to one of a variety of laser, placebo or control groups under randomized, blinded conditions. Analysis of negative peak latency differences using analysis of variance showed small (approximately 0.4 ms) but significant increases in latencies as a result of direct laser irradiation, and, where two-site recording was used, distal to the site of irradiation. No such differences were seen in the other experimental groups. These results show that laser irradiation applied to intact skin at the parameters used here may produce a direct, localized effect upon conduction in underlying nerves. PMID- 8003308 TI - Expression of c-fos in the ovine brain following different types of stress, or central administration of corticotrophin-releasing hormone. AB - Expression of c-fos protein was examined in the brains of sheep (n = 2 per treatment) subjected to physical stress in a transport simulator, the psychological stress of isolation, insulin-induced hypoglycaemia or intracerebroventricular (I.C.V.) injection of ovine corticotrophin-releasing hormone (CRH). As control procedures, two sheep were given I.C.V. injections of saline and one animal received no treatment. Fos expression was induced in the hypothalamic paraventricular nucleus by transport simulation, isolation and hypoglycaemia, and also in the hypothalamic supraoptic nucleus by hypoglycaemia. Labelled nuclei were also seen in the brainstem in the region of the area postrema following transport simulation, isolation and insulin treatments. These results indicate that c-fos expression in the ovine CNS is a useful marker for the identification of brain regions activated by stressors. PMID- 8003309 TI - Effects of gadolinium on length-dependent force in guinea-pig papillary muscle. AB - The degree to which stretch-activated channels operate during physiological length changes in multicellular heart preparations, or how much the channels could contribute to length-dependent activation, is not known. We studied the relationship between muscle length and contractile force in guinea-pig papillary muscles superfused with gadolinium chloride (10 microM), a stretch-activated channel blocker, and compared the effects to those with nifedipine (0.25 microM), a calcium channel blocker. Gadolinium reduced contractile force statistically significantly more at the longer muscle lengths than at the short muscle lengths. This did not apply with nifedipine, although a marginally greater effect at longer lengths was perceptible. The results can only partly be explained by gadolinium having a non-specific action via the calcium channel, or Na(+)-Ca2+ exchange, and are consistent with the possibility that stretch-activated channels contribute to length-dependent activation in cardiac muscle, and thus to 'Starling's Law of the Heart'. PMID- 8003310 TI - Effect of hypoxia on arterial potassium concentration at rest and during exercise in man. AB - Hypoxia has been reported to increase arterial potassium concentration ([K+]a) in anaesthetized cats (Paterson, Estavillo & Nye, 1988). The purpose of this study was to determine whether this phenomenon occurs in humans. The effect of hypoxia on [K+]a was measured in ten male subjects, at rest and during light exercise, before and after 8 weeks of physical training. The [K+]a increased by 0.15 +/- 0.04 mM (mean +/- S.E.M.) at rest, when end-tidal PO2 (PET,O2) was lowered from 100 to 51 +/- 1.6 Torr, and by 0.10 +/- 0.02 mM during exercise, when PET,O2 was lowered from 100 to 66 +/- 6.2 Torr. Physical training did not alter the rise in [K+]a significantly. The magnitude of this effect is small in comparison with that of exercise-induced hyperkalaemia, and is unlikely to be of great physiological significance at moderate levels of hypoxia. PMID- 8003311 TI - Presynaptic inhibition by neuropeptide Y of slow inhibitory synaptic transmission in submucous neurones of guinea-pig caecum. AB - The occurrence and disposition of immunoreactivity for neuropeptide Y (NPY) was investigated in the submucosa of guinea-pig caecum. There were few NPY immunoreactive neurones but intraganglionic varicose fibres were so numerous and strongly immunoreactive that some somata may have been obscured. In each neurone tested, exogenous application of NPY (1-100 nM) depressed the duration and amplitude of the slow inhibitory postsynaptic potential. In contrast, NPY (1-300 nM) had no effects on the resting membrane potential, input resistance and fast and slow excitatory synaptic transmission. PMID- 8003312 TI - Calcium store depletion in dimethyl BAPTA-loaded human platelets increases protein tyrosine phosphorylation in the absence of a rise in cytosolic calcium. AB - The endomembrane Ca(2+)-ATPase inhibitor, thapsigargin, was used to deplete the intracellular Ca2+ stores of fura-2-loaded human platelets. In control cells, thapsigargin evoked a rise in cytosolic [Ca2+] and a substantial increase in protein tyrosine phosphorylation. Thapsigargin also evoked an increase in tyrosine phosphorylation in cells co-loaded with fura-2 and the Ca2+ chelator dimethyl BAPTA, such that the rise in cytosolic [Ca2+] was abolished. These data support the existence of a tyrosine phosphatase regulated by the Ca2+ content of the intracellular store, a requirement of the putative model for reciprocal control of Ca2+ entry by cytosolic and store [Ca2+] via protein tyrosine phosphorylation. PMID- 8003313 TI - The effect of alcohol on physiological tremor. AB - Ethanol reduces the size of essential tremor. We here show that, contrary to a recent report, ethanol also causes a large decrease in the size of physiological tremor. As in the case of essential tremor, the frequency is not changed. The reduction in tremor probably explains the well-known link between certain types of skilled activity and alcohol consumption. PMID- 8003314 TI - Effects of cyclosporin A on hair. AB - Cyclosporin A (CSA) is an immunosuppressive agent that has provided new approaches in transplantation medicine and in the treatment of autoimmune diseases. One of the most common dermatological side effects of oral CSA is dose dependent hypertrichosis. This stimulating effect on hair growth encouraged a number of investigators to use CSA not only in the treatment of alopecia areata (AA), but also in male pattern alopecia (MPA). While oral application proved successful, the beneficial effect of topical application was very limited in both AA and MPA. PMID- 8003315 TI - Recent advances in hair transplantation. AB - Mini- and micrografts produce esthetic results in the treatment of alopecia androgenetica which cannot be achieved using conventional methods. It is for this reason that they should be used exclusively. Their fineness furthermore opens up new vistas in plastic reconstructive surgery, making treatments possible which were previously inconceivable. PMID- 8003316 TI - Experimental approaches for the reconstitution of hair in vitro. AB - When plucked follicles were cultured together with isolated dermal papillae in a collagen gel matrix, outer root sheath cells (ORSCs) grew more rapidly and actively than without the papillae. Cultured dermal papilla cells also activated the colony growth of ORSCs in vitro. These results may suggest the existence of some papilla-derived factor(s) activating the growth of ORSCs. In cultures of excised whole follicles whose dermal papilla had been removed, epithelial cells of bulb matrix origin grew out from the bulbous portion, and formed spikes. When a dermal papilla was implanted close to the follicle, the spikes elongated toward the papilla, and finally reached and surrounded it. This finding suggests that dermal papillae may produce some factor(s) attracting epithelial cells of hair bulb origin. In cultures of excised whole follicles, when the dermal papilla remained originally positioned in contact with the hair bulb matrix, the hair and follicle elongated for more than 1 week. But when the dermal papilla was detached from the bulb matrix, the matrix cells proliferated into the gel and formed a hair-follicle-like structure (folliculoid). In cultures of excised whole follicles whose papilla-matrix junction had been damaged by dispase, elongation of the hair and follicle was almost completely suppressed. Thus, the attachment of the dermal papilla to the bulb matrix appears to be necessary for normal hair and follicle growth. PMID- 8003317 TI - Hair follicle stem cells: characteristics and possible significance. AB - All four of the principle dermal and epidermal cell types from the adult hair follicle (dermal papilla and sheath, germinative epidermal and outer root sheath) can now be grown in culture. The germinative epidermal cells from the source of the hair fibre appear to be the most visually distinctive of these populations, but all four can be morphologically, synthetically and behaviourally distinguished from general interfollicular skin cells. The germinative population also most obviously exhibit many classical stem cell attributes, but the interactive and inductive capabilities of all of the cell types, in addition to their multipotential natures, highlights that they all share an intriguing level of developmental flexibility. PMID- 8003318 TI - Androgen action in cultured dermal papilla cells from human hair follicles. AB - Androgens are major regulators of human hair growth with paradoxically different effects on hair follicles depending on their body site. They stimulate terminal growth in many regions including the face, have no effect on eyelashes, but may cause inhibition and balding on the scalp in genetically disposed individuals. How this occurs is unknown. However, androgens may act on the hair follicle via the cells of the dermal papilla; these would then influence the other cells of the hair follicle by altering the production of regulatory substances such as growth factors and/or extracellular matrix components. Therefore, primary lines of dermal papilla cells have been established from androgen-sensitive hair follicles, such as beard, and control, relatively androgen-independent, non balding scalp cells and their mechanism of androgen action has been compared. Isolated beard dermal papillae were larger than those from scalp follicles. Although dermal papilla cells did not respond to in vitro androgens by alterations in growth, androgen-dependent dermal papilla cells contained higher levels of specific, low capacity, high affinity androgen receptors than non balding scalp cells. The ability of the cells to metabolise testosterone to 5 alpha-dihydrotestosterone in culture also varied in parallel to that predicted from studies of hair growth in the 5 alpha-reductase deficiency syndrome. These results support the hypothesis that androgens act via the dermal papilla. They also show that dermal papilla cells retain differences in gene expression in culture which appear to correspond with their androgenic response in vivo. Further studies of such cells should help elucidate why bald men can grow beards! PMID- 8003319 TI - Vellus hair follicle-derived keratinocyte culture: a new experimental model in human hair research. AB - Biological and biochemical mechanisms of hair growth are difficult to study in vivo; therefore the development of in vitro models is of great interest. Today, we have of our disposal reliable techniques to cultivate cell populations and entire components of terminal hair follicles; however, in vitro culture models for cells derived from vellus hair follicles have not yet been established. In this study, we present a technique for cultivating vellus hair follicle-derived keratinocytes (VHK) and we present first findings on their characterization. Primary cultures of VHK were obtained as outgrowths of cultured intact vellus hair follicles prepared by microsurgical means after incubation of full-thickness human skin with dispase. (1) VHK cultures reached confluency after 16-20 days and 3-4 subcultures were possible. (2) VHK were characterized as epithelial cells by light and electron microscopy. (3) A multi-layered stratified epithelium with 8 10 cell layers was observed by electron microscopy presenting abundant keratinosomes in individual cells in contrast to outer root sheath keratinocytes. (4) Synthesis studies of two glycoproteins characteristic for undifferentiated (gp 38) and for differentiated (gp 80) keratinocytes revealed higher synthesis levels for gp 80 and lower levels for gp 38 in VHK as compared to normal epidermal keratinocytes in vitro. These findings suggest a distinct morphologic and differentiation pattern of VHK in culture. This experimental model provides a new tool to study mechanisms of hair growth regulation in vellus hair follicles and to compare them to those of terminal hair follicles. PMID- 8003320 TI - Androgens affect the activity of human sebocytes in culture in a manner dependent on the localization of the sebaceous glands and their effect is antagonized by spironolactone. AB - To investigate the varying response of the pilosebaceous unit to androgens functional studies were performed on the effects of testosterone and 5 alpha dihydrotestosterone on cultured human sebocytes derived from different skin regions. In addition, the effect of spironolactone on the proliferation of androgen-stimulated human sebocytes derived from facial skin was evaluated. Testosterone (10(-11) to 10(-5) M), 5 alpha-dihydrotestosterone (10(-11) to 10( 5) M) and spironolactone (10(-12) to 10(-7) M) were added for 10 days as single substances or in combinations to human sebocytes in secondary culture maintained in a serum-free medium. Cell proliferation was assessed using a fluorometric assay. Intracellular lipids were extracted from sebocytes treated with androgens (10(-7) M) for 10 days after confluency. Testosterone inhibited the proliferation of sebocytes derived from the legs with a 50%-inhibitory concentration at 10(-5) M and induced a 50% decrease of intracellular lipids. In contrast, 5 alpha dihydrotestosterone stimulated the activity of leg sebocytes with a 50% increase of proliferation at 10(-5) M, and a 175% increase of intracellular lipids. On the other hand, the proliferation of facial sebocytes was significantly stimulated by testosterone with a 50%-stimulatory concentration at 10(-6) to 10(-5) M and mostly by 5 alpha-dihydrotestosterone with a 50% enhancement at 10(-8) to 10(-7) M. Spironolactone inhibited the proliferation of facial sebocytes in a dose dependent manner with a 25%-inhibitory concentration at 10(-9) M. Simultaneous treatment of facial sebocytes with spironolactone and testosterone or 5 alpha dihydrotestosterone resulted in decreased proliferation when compared to the growth obtained under androgens alone.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8003321 TI - The human hair follicle engages in glutaminolysis and aerobic glycolysis: implications for skin, splanchnic and neoplastic metabolism. AB - On maintenance in supplemented Williams E medium, human hair follicles grow at the normal rate, and retain their normal anagen morphology, for up to 10 days. This permits us to study their metabolism under near-physiological conditions. The ATP content of freshly isolated follicles was 124.4 +/- 10.6 pmol/follicle (mean +/- SEM; n = 50). The energy charge was 0.81 +/- 0.08 and the glycogen content 2.3 +/- 0.3 nmol/follicle. These did not alter significantly during any metabolic studies, which were performed for up to 6 h in supplemented Williams E medium. We found that the major fuel was glucose, which at physiological concentrations yields 5.47 +/- 0.77 nmol ATP/follicle/h, but 90% of the glucose was metabolised to lactate, and only 10% oxidised. Glutamine was also an important fuel, generating 2.16 +/- 0.33 nmol ATP/follicle/h, but this too was largely metabolised to lactate rather than oxidised. Lipid fuels such as palmitate or beta-hydroxybutyrate only yielded 0.72 +/- 0.15 and 0.72 +/- 0.14 nmol ATP/follicle/h, respectively, and their oxidation did not inhibit glucose utilisation. No glucose-fatty acid cycle operates in the hair follicle, therefore, but a glucose-glutamine cycle does, since the presence of glutamine will inhibit glucose utilisation. PMID- 8003322 TI - Organotypic cocultures as models to study cell-cell and cell-matrix interactions of human hair follicle cells. AB - In the hair follicle complex interactions of specialized epithelial and mesenchymal cells as well as extracellular components are crucial for regulation of proliferation and differentiation. In order to mimic this situation in vitro, techniques to cultivate follicular cells such as outer root sheath (ORS) cells, hair matrix cells (HMC) and hair papilla cells (HPC) were developed. Human dermal fibroblasts (HDF) and HPC markedly enhanced proliferation of ORS cells when cocultured spatially separated in a two-chamber system, which was more pronounced with postmitotic than with mitotic mesenchymal cells. In organotypic cocultures of ORS cells on HDF- or HPC-populated collagen gels lifted at the air-medium interface, stratified epithelia developed largely reminiscent of the epidermis. The morphology was well structured and differentiation markers were expressed (e.g. suprabasal keratins, filaggrin, involucrin, basement membrane components). Both proliferation and differentiation were dependent on the presence of HDF or HPC. When grown embedded in extracellular matrix (Matrigel) without HDF, ORS cells formed large spheroids with inward directed differentiation. Also herein HDF or HPC sustained both cell growth and balanced, epidermistype differentiation. While in organotypic cocultures with HDF, HMC also organized into stratified epithelia, epidermis-type stratification was prevented by HPC. Similarly, in the presence of HDF, HMC in Matrigel formed keratinizing spheroids, whereas this was largely suppressed in the presence of HPC. However, hair-type differentiation was not observed, suggesting a crucial role of other yet unknown components or of the surrounding matrix. PMID- 8003323 TI - Biochemical mechanisms regulating human hair growth. AB - The human hair follicle cycles in active growth and resting phases controlled by a complex network of biochemical processes, yet to be fully understood. It is well known that hair follicles on scalp respond to androgens by a shortening of the anagen growth phase causing hairs to regress to a finer, thinner texture. The target tissue androgens, testosterone, and dihydrotestosterone can circulate systemically to skin or can be formed locally in hair follicles and sebaceous glands by specific enzymes in the steroid cascade. Kinetic constants have been evaluated for several enzymes which mediate dihydrotestosterone formation, including 5a-reductase, and the cytochrome P-450 aromatase enzyme in isolated human hair follicles and sebaceous glands from scalp of men and women with androgenetic alopecia. The levels of these enzymes differed between men and women, and from frontal versus occipital sites within the same patient, indicating that similar steroid mechanisms may be taking place in men and women, but the amount or level of enzymes vary, perhaps explaining why men have more severe patterns of hair loss than women. Knowing the differences between men and women with androgenetic alopecia could shape more effective treatment options in the future. PMID- 8003325 TI - Hormonal basis of male and female androgenic alopecia: clinical relevance. AB - A broad range of hormones was determined in males and females with androgenic hair loss (AH). The androgens testosterone, androstenedione, dehydroepiandrosterone sulfate, 17-hydroxyprogesterone and sex hormone binding globulin were evaluated in 65 male and 46 female patients. Besides estradiol (E2), cortisol (F), and the hypophyseal hormones LH, FSH, and prolactin (PRL) were investigated. Hormone levels were compared with those of 58 age-matched male and 45 female controls. In 38 of the 46 female AH patients, hypophyseal function was moreover evaluated by the 'TRH test', which detects slight, secondary hypothyroidism and/or hyperprolactinemia. Our findings showed a significant elevation of F in both male and female AH patients compared to controls, pointing to the suprarenes as a contributing factor in AH. This is confirmed by the observation of exacerbated AH in periods of increased stress. Concerning specifically male androgens, a significant elevation of androstenedione was noted. The mainly peripheral activity of this hormone and elevated E2 levels in males stress the importance of androgen metabolism especially at the peripheral level. Additional TRH tests in females demonstrated significant hypophyseal hypothyroidism. Multilayered interaction between thyroid hormones and androgens may contribute to the development of AH in hyperthyroid patients. Another significant finding was elevated PRL after TRH stimulation. Thus, the androgen stimulating effect of PRL may also play a role in female AH. Our findings show multilayered hormonal influences in AH. Broad-range hormone determination demonstrated a differentiated hormonal situation in this disorder. PMID- 8003324 TI - Cell kinetics of anagen scalp hairs under physiological and pathological conditions. AB - The cell kinetics of anagen scalp hair bulbs taken by punch biopsies from healthy male volunteers (n = 50) were determined at defined bulbar hair segments using microdissection and DNA flow cytometry. The highest proliferative activity (S phase) was measured within the lower most bulbar segment (14.0%) but decreased to the Auber's segment (7.6%) and to the isthmus segment (5.9%). The results support histoautoradiographic data demonstrating most of the proliferative activity in the hair bulb below the Auber's level [1]. Furthermore, cell kinetic data of dissected anagen hair bulbs segmented at Auber's level from an androgen-sensitive scalp area were studied in male pattern baldness (n = 15, Hamilton IV) and hirsutism (n = 13). The results revealed a significant increase of S phase cells in male pattern baldness (8.9%) compared to healthy males (n = 10, 7.9%) as well as in hirsutism (10.2%) compared to healthy females (n = 10, 7.5%). In hirsutism the percentages of S phase cells ran parallel to the plasma levels of dehydroepiandrosterone sulfate whereas no correlation to testosterone could be proved. Similar, 6 hypothyroid and 6 hyperthyroid patients were studied. In hyperthyroidism an increase of S phase values (10.3%) was found, while it decreased in hypothyroidism (6.1%). A correlation between the height of S phase and plasma triiodothyronine level was noted. Our studies demonstrate that DNA flow cytometry is a suitable method for the evaluation of physiological or hormonal influences on cell cycle kinetics of human anagen hair bulbs in vivo. PMID- 8003326 TI - The phototrichogram: analysis of some technical factors of variation. AB - Photographic methods for hair evaluation are frequently proposed as an alternative to more invasive methods (trichogram or biopsy). The reliability in terms of quantitative follow-up of hair growth has not been evaluated properly. We report results of comparative studies of scalp hair evaluation with various photographic methods. Statistically significant findings were a better detection of scalp hairs using the original enlargement x 3 as compared to x 2 (212 vs. 167 hair follicles/cm2) and a more acceptable estimate of linear hair growth rate with 'scalp immersion proxigraphy' (SIP) (0.317 mm/day) as compared with classical phototrichogram pictures where this variable was underestimated by 30% on average (0.27 mm/day). SIP-generated linear hair growth rates were very close to the micrometric method (0.37 mm/day). Therefore SIP x 3 images appear preferable for hair growth monitoring during clinical trials. PMID- 8003327 TI - Photoageing of hair fiber and photoprotection. AB - Examination by transmission electron microscopy of hair exposed to sunlight has revealed important damage. Findings indicate an alteration of various cell components. Damage occurs in the cuticle and leads to its loss. Separation of macrofibrils and destruction of melanin pigments result in cortex damage. Some of the chemical and physical changes which occur in hair exposed to sunlight were studied: formation of carbonyl groups, cystine destruction, modification of the proteins obtained by reduction of the disulfide bonds, losses in mechanical strength and discoloration are discussed. Effects of UV and visible radiations were studied. All of them cause modification in hair properties. Experiments with artificial light sources were carried out to reproduce these alterations. The role of water during exposure was studied. In particular, discoloration of brown hair is largely affected by it. We showed that Xenon lamps were useful to follow the photooxidation of hair and simulate natural alterations. The properties of some protective materials were examined. PMID- 8003328 TI - 2-in-1 shampoo technology: state-of-the-art shampoo and conditioner in one. AB - Consumers have expressed a need for cleaning and conditioning in one step. Conventional shampoo technology using anionic surfactants and cationic conditioners results in charge interaction and complexing of the ingredients. Neither shampoo nor conditioners achieves the desired result. The successful solution was to incorporate charge neutral dimethicone conditioning ingredients, suspended as microfine droplets within complex crystal lattices, into anionic surfactant shampoo technology. The same solution has also been applied to amphoteric surfactant systems. This provides complete cleaning, and hair conditioning fully equal to separate conditioners without the problems of sebum interactions and conditioner build-up. This was achieved by keeping the dimethicone in suspension throughout the shampoo process. During rinsing, excess water breaks the crystalline lattice and allows deposition of the dimethicone droplets onto the hair. Full cleaning and conditioning are, therefore, achieved in one application. Dimethicone build-up is not encountered as subsequent washes first remove soil and previously deposited dimethicone. Neither do neutral dimethicones show any reactions with sebum. The development of effective 2-in-1 technology has had a major impact on shampoo technology and consumer habits and practices. This has significantly changed the way consumers care for their hair. PMID- 8003329 TI - Cells in the bulge of the mouse telogen follicle give rise to the lower anagen follicle. AB - The slow-cycling cells in the bulge of the outer root sheath may represent stem cells for the hair follicle. With each new anagen (growing) phase bulge cells would give rise to a population of transient-amplifying cells which differentiate into outer root sheath and matrix keratinocytes. The lowermost part of the telogen (resting) follicle is composed of bulge cells lying in close proximity to the dermal papilla. In the mouse the first hair follicle growth is characterized by rapid follicular neogenesis, but the second and third growth cycles follow the normal follicular growth pattern. We have examined activity of cells in the bulge at the onset of anagen (growing phase) in the third hair cycle in Sencar mice, by treating animals at the end of the second telogen with colchicine to localize mitotic activity in the hair follicle. Mitoses were only seen in bulge cells during early anagen. This confirms that they proliferate transiently, solely at the onset of anagen and strongly supports the suggestion that bulge cells are the origin of the whole lower follicle in anagen. PMID- 8003330 TI - Hair cycle and alopecia. AB - Male pattern alopecia is the outcome of profound modifications in the duration, succession and frequency of hair cycles. These phenomena were studied by phototrichogram in 10 male subjects, with or without alopecia, over a period of 15 years. Almost 10,000 hair cycles were accounted for, yielding a detailed picture of the alopecia condition: (1) A decrease in the duration of anagen for a certain proportion of hairs, a proportion which increases in size, the more advanced the alopecia; the result of this premature transformation from anagen to telogen is an increase in the rate of hair loss. (2) A parallel decline in hair diameter. (3) Longer latency periods between the fall of a hair and the onset of regrowth, leading to a reduction in the number of hairs present on the scalp surface. The shorter finer hairs are absent more frequently and absent for longer periods and this contributes to the effect of alopecia. PMID- 8003331 TI - Tumors of the pilosebaceous unit. AB - Appendage tumors of the pilosebaceous apparatus are relatively rare, and their clinical aspect is usually nonspecific. In most cases pilosebaceous tumors are benign; however, malignant neoplasias (e.g. trichilemmal carcinoma, malignant pilomatricoma) have been described. In the present review we propose the classification of pilosebaceous tumors by degree and by direction of differentiation and by histological configuration. Three different histological patterns have to be distinguished: tumors with central dilated hair follicle, tumors consisting of epithelial islands and keratotic cysts in the corium and neoplasias with predominantly mesenchymal components surrounding epithelial formations. Careful histopathological examination of pilar appendage tumors will help to classify the wide range of clinically and histologically different tumors and to establish the exact diagnosis. PMID- 8003332 TI - Cancer risk and exposures to carcinogens in hairdressers. AB - A number of epidemiologic studies have focused on the risk of bladder and lung cancer in hairdressers and beauticians, and the risk of breast cancer, and bladder cancer associated with the private use of hair dyes has also been addressed. The most consistent, although by no means unequivocal, finding is the increased risk of bladder cancer in male hairdressers. The use of brillantine containing p-dimethylaminoazobenzene could be suggested as a relevant exposure. We present recent incidence data on bladder cancer in Danish hairdressers showing relative risk (RR) = 2.05 (men) and RR = 1.75 (women) in 1970-1980 and RR = 1.17 (men) and RR = 0.88 (women) in 1981-1987. Furthermore, in female hairdressers, the risk of non-Hodgkin's lymphoma was increased for the whole period of 1970 1987. PMID- 8003333 TI - alpha-Interferon cream restores decreased levels of Langerhans/indeterminate (CD1a+) cells in aged and PUVA-treated skin. AB - Langerhans/indeterminate (CD1a+) cells are known for their role in stimulating T lymphocyte-dependent immune reactions. They are normally present in the skin and are modified in a variety of different pathological and physiological events, including aging. Linear decrease of CD1a+ cells with aging (both true aging and photoaging) is considered the most important cause of reduced immunosurveillance in aged old skin of the elderly. Recently it has been suggested that alpha interferon might have an effect on increasing levels of dendritic cells in aged and photoaged skin. We studied biopsies from the preauricular area in 15 subjects (5 subjects aged 18-21 years, 5 aged 57-75, and 5 aged 30-45 who underwent PUVA therapy, total irradiation 120 J/cm2) before and after the application of alpha interferon cream. Our findings show that dendritic cells are significantly decreased in the 57- to 75-year-old group compared to the 8- to 21-year-old group. After PUVA therapy we also found a decrease in Langerhans cells. Our study shows that the application of alpha-interferon cream induces an increase in cutaneous CD1a+ cells and HLA-DR+ cells in both older subjects and subjects who have undergone PUVA therapy. On the basis of these results, one could hypothesize that alpha-interferon cream may have some beneficial effects on photoaging reduced immunosurveillance. PMID- 8003334 TI - Comparison of thymoxamine permeation between hairless rat and horse penile mucous membrane using an in vitro diffusion model. AB - Moxisylyte (or thymoxamine) administered intracavernously is known to improve erection in organically impotent patients. Prior to drug administration by percutaneous route, we have to define its in vitro permeation parameters after application of thymoxamine on both rat skin and horse penile mucous membrane. 24 h after drug application, the percentages of thymoxamine which diffused through the penile mucous and the rat skin were 88 and 75%, respectively. Thymoxamine flux varied according to the biological membrane tested. With regard to the penile mucous membrane, a maximal flux (1,774 nmol.h-1.cm-2) was observed 2.5 h after drug application, whereas for the rat skin a maximal flux (657 nmol.h-1.cm 2) was noted at 3.5 h. Thymoxamine flux decreased rapidly in the penile mucous membrane. This decrease was slower when thymoxamine penetrated the rat skin; the difference could be due to a different morphology of the tested biological membranes. In contrast to the rat skin, the external keratinized layer was absent in the penile mucous membrane. In conclusion, the ability of thymoxamine to penetrate easily and rapidly the biological membrane, and particularly the penile mucous membrane, suggests that thymoxamine could reach the pharmacological target represented by the corpus cavernosum of the penis. PMID- 8003335 TI - Plasma concentrations after three different doses of topical isotretinoin. AB - The aim of the study was to investigate the plasma concentrations of isotretinoin and its metabolites, at three doses and after single and multiple topical applications of isotretinoin gel (0.05%) in hairless rats. We used a highly sensitive HPLC method for simultaneous determinations of these compounds, with a detection limit of 2 ng/ml in plasma. Isotretinoin and its metabolites were detected after single and multiple cutaneous applications of overdosing (2,000 mg) of isotretinoin gel up to 24 h after the single dose and after the last dose. The plasma concentrations of these compounds were below the limit of quantification in all the animals at all times for the 200- and 20-mg doses. PMID- 8003336 TI - Measurement of color parameters of psoriatic plaques by narrow-band reflectance spectrophotometry and tristimulus colorimetry. AB - Color parameters were measured on 50 psoriatic plaques in 10 patients, after scoring the amount of scales on them by inspection, with a narrow-band reflectance spectrophotometer (erythema/melanin index expression) and tristimulus colorimeter (CIE L*a*b* expression). Both erythema index a* (redness) were highest in the group of erythematous plaque with little scale (twice as high as in controls) and decreased significantly as the plaques were covered with thicker scale, while L* (brightness) changed in just the opposite fashion of a*. These portable 'color indicators' can be utilized to express the appearance of psoriatic plaques quantitatively, especially the extent of erythema and the amount of the scale on it. PMID- 8003337 TI - Depletion of murine CD4+ T lymphocytes prevents antigen-induced airway hyperreactivity and pulmonary eosinophilia. AB - The pathogenesis of asthma remains unclear. An in vivo murine model of antigen induced airway hyperreactivity and inflammation was developed to investigate the possibility, suggested by a wealth of descriptive human data, that alterations in immunoregulation are important in the genesis of airway hyperreactivity. A/J mice developed airway hyperreactivity and markedly increased numbers of pulmonary inflammatory cells following intraperitoneal sensitization and intratracheal challenge with sheep red blood cells. Notably, eosinophils were a prominent component of the inflammatory infiltrate. The dependence of these phenomena, both pathologic and functional, on CD4+ T lymphocytes was investigated by in vivo depletion of CD4+ cells using the anti-CD4 mAb GK1.5. When administered before antigen challenge, GK1.5 completely prevented both airway hyperreactivity and the infiltration of eosinophils. This model provides the first direct demonstration of the dependence of airway hyperreactivity upon CD4+ T lymphocytes, and the results are consistent with the possibility that eosinophils are effectors of this response. PMID- 8003338 TI - The effect of particle inhalation on macrophage number and phagocytic activity in the intrapulmonary conducting airways of hamsters. AB - The number and functions of macrophages in the lungs are crucial factors for prevention and development of lung disease caused by inhaled particles. To examine whether airway macrophages are attracted to the site of particle deposition and what proportion of these macrophages is involved in phagocytosis, aerosols of 6-microns polystyrene particles (PSP) were inhaled by Syrian Golden hamsters under controlled conditions through an inhalation tubule and their lungs were fixed by intravascular perfusion within 20 min (PSP-1, PSP-1a), 40 min (PSP 2), and 24 h (PSP-3) after the beginning of the inhalation. The number and the phagocytic activity of airway macrophages were studied in situ with a fractionator, a stereologic method, on light microscopic sections. No significant increase in macrophage number was detected for the groups PSP-1 and PSP-1a. The increase for group PSP-2 was, however, between 2- and 3-fold, whereas for group PSP-3 the increase was between 1.5- and 2.5-fold with respect to control animals, which had inhaled ambient air through an intubation tubule (C-2) and whose lungs had been fixed after 40 min. There were no significant differences among the four groups with respect to the proportion of airway macrophages that had phagocytized polystyrene microspheres. Twelve to fifteen percent of the macrophages were found to be involved in phagocytosis. In the case of the mean number of particles per phagocytizing macrophage, there was a significant decrease for the PSP-3 group with respect to the pool of the three groups PSP-1, PSP-1a, and PSP-2 taken together. These studies demonstrate (1) that airway macrophages are rapidly recruited to the sites of particle deposition and (2) that only a small proportion of very active macrophages contributes to the clearance of particles, suggesting a great potential of airway macrophages to interact with many more particles than the hamsters were exposed to in this study. PMID- 8003339 TI - Cell number and distribution in human and rat airways. AB - Morphometric procedures were used to determine the number of cells, cell volume, cell diameter, and surface areas of the airways in human and rat lungs. Nuclear sizes of epithelial cells from human bronchi were significantly larger than other lung cell nuclei. The average volume of human ciliated cell nuclei was 310 +/- 30 microns 3 and 167 +/- 12 microns 3 in bronchi and bronchioles, respectively. The smaller nuclei of human bronchioles were comparable to those of alveolar cells. In the pseudostratified epithelium of human bronchi, basal cells had a large surface area in contact with the basement membrane (51.3 +/- 4.6 microns 2 per cell) when compared with ciliated (1.1 +/- 0.1 microns 2), goblet (7.6 +/- 1.2 microns 2), or other secretory cells (12.0 +/- 2.1 microns 2). In the first four airway generations distal to the trachea, basal cells account for 30% of the cells in human airway epithelium and 2% of the cells in rat airway epithelium. Total airway surface area from trachea to bronchioles was 2,471 +/- 320 and 27.2 +/- 1.7 cm2 in human and rat lungs, respectively. These direct measurements of airway surface area are less than half of the estimates based on current lung models. The total number of airway epithelial cells were 10.5 x 10(9) for human and 0.05 x 10(9) for rat lungs. For both species, there were 18 times more alveolar cells than bronchial epithelial cells. PMID- 8003340 TI - Regulation of lung branching morphogenesis by bombesin-like peptides and neutral endopeptidase. AB - The expression of bombesin-like peptides (BLPs) by pulmonary neuroendocrine cells is transiently upregulated during lung development. A functional role for BLPs is supported by their ability to stimulate lung growth and maturation both in vitro and in vivo during the late stages of lung development. In addition, the cell membrane-associated enzyme CD10/neutral endopeptidase 24.11 (CD10/NEP), which inactivates BLPs and other regulatory peptides, is also expressed by developing lungs and modulates the stimulatory effects of BLPs on lung growth and maturation. We hypothesized that, in addition to expressing BLPs and CD10/NEP, embryonic lungs must express BLP receptors, and that BLPs may also regulate processes that occur during early lung development such as branching morphogenesis. Using reverse transcriptase-polymerase chain reaction and oligonucleotide primers designed for amplifying a BLP receptor originally isolated from Swiss 3T3 mouse fibroblasts, we found that embryonic mouse lungs express a similar BLP receptor mRNA during the pseudoglandular stage of lung development when branching morphogenesis take place. Subsequently, we evaluated the effects of ligands for this BLP receptor using embryonic mouse lungs in an in vitro model of lung branching morphogenesis. We found that, in comparison with control lungs, treatment with bombesin (1 to 100 nM) resulted in a modest increase in clefts or branching points. In contrast, embryonic mouse lungs treated with the BLP analog [Leu13-psi(CH2NH)Leu14]bombesin (1 microM), which also binds to this BLP receptor but has predominantly antagonistic effects, demonstrated fewer branching points.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8003341 TI - Leukotriene B4 stimulates human polymorphonuclear leukocytes to synthesize and release interleukin-8 in vitro. AB - Interleukin-8 (IL-8) is a potent chemotactic protein for polymorphonuclear leukocytes (PMN). Here we examine whether PMN synthesize and release IL-8 in response to stimulation by leukotriene B4 (LTB4). PMN isolated from normal heparinized peripheral human blood were incubated in RPMI culture medium at 37 degrees C in 5% CO2, with and without LTB4. The culture supernatants were tested for IL-8 bioactivity through chemotactic activity measurements with and without neutralizing anti-IL-8 serum. Immunoreactive IL-8 was quantified by ELISA, and de novo IL-8 synthesis was evaluated by metabolic labeling with [35S]cysteine followed by immunoprecipitation. LTB4 stimulated PMN to produce IL-8 in a dose- and time-dependent manner. The IL-8 concentrations reached maximal levels after 16 h of incubation with LTB4. Significant increases in IL-8 production occurred with LTB4 doses of 10 to 1,000 nM/ml. Immunoprecipitation of labeled IL-8 documented new synthesis of IL-8 by LTB4-treated PMN. Northern blot analysis of total RNA from PMN using a 30 mer oligonucleotide for IL-8 demonstrated increased mRNA expression in LTB4-stimulated PMN compared with untreated PMN. These data show that peripheral blood PMN can be stimulated by LTB4 to synthesize and secrete biologically active IL-8. PMN and other cells capable of producing LTB4 may induce IL-8 protein production by inflammatory PMN and thereby amplify or perpetuate the acute inflammatory response by recruiting additional PMN into an inflammatory site. PMID- 8003342 TI - A mouse model of lung injury induced by microbial products: implication of tumor necrosis factor. AB - Mice of the C57BL/6 strain were injected with bacterial lipopolysaccharide (LPS) followed by formylnorleucyl-leucyl-phenylalanine (FNLP) by the intraperitoneal route; markers of acute lung injury were examined in mice given a fusion protein of soluble human tumor necrosis factor-alpha (TNF-alpha) receptor (p80) linked to the Fc portion of human IgG (TNFR:Fc) or excipient. Challenge with LPS/FNLP elicited an adult respiratory distress syndrome-like pathology characterized by sharp increases in levels of lactate dehydrogenase (LDH) and total proteins in bronchoalveolar lavage as well as in lung myeloperoxidase (MPO) content at 16 and 20 h after challenge. Infusion of 1 mg of TNFR:Fc 2 h before challenge very significantly abrogated the increases in LDH, protein levels, and MPO. Histologic analysis revealed that LPS/FNLP infusion resulted in an intravascular neutrophil agglomerate and perivascular/peribronchial damage; the extent of tissue lesions was significantly reduced, but not abrogated, by TNF-alpha depletion. There were moderate levels of antigenic TNF-alpha in lung homogenates at 16 and 20 h after challenge, not affected by infusion with TNFR:Fc. No bioactive TNF-alpha was detected in lung homogenates of challenged mice given TNFR:Fc. High levels of antigenic interleukin-6 (IL-6) were found in lung homogenates of challenged mice treated with TNFR:Fc or with diluent. Elevated levels of antigenic IL-6 and TNF alpha were found in sera of challenged mice at 16 and 20 h after injection; TNFR:Fc-treated mice had a higher level of antigenic TNF-alpha than did challenged mice given diluent, but it was not bioactive.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8003343 TI - Characterization of GTP-binding proteins coupled to inhibition of adenylyl cyclase in guinea pig tracheal epithelial cells. AB - Many important airway epithelial cell functions are regulated by intracellular cAMP. Adenylyl cyclase, the enzyme that synthesizes cAMP, is under dual regulation in many cells, but muscarinic agonists have not been shown to inhibit adenylyl cyclase in human and dog epithelial cells, despite the presence of muscarinic receptors. We question whether the lack of inhibition was related to the absence of a component of the inhibitory pathway or a lack of coupling between the components. The GTP-binding regulatory proteins (G proteins) that regulate adenylyl cyclase activity in airway epithelium have not been well characterized. We used primary cultures of guinea pig tracheal epithelial cells as a model system and identified the G proteins that modulate adenylyl cyclase activity. Immunoblot analysis demonstrated the presence of alpha subunits corresponding to stimulatory (Gs alpha) and inhibitory [Gi alpha (2) and Gi alpha (3)] G proteins as well as beta chains. These G proteins were functionally coupled to stimulation and inhibition of adenylyl cyclase in epithelial membrane preparations. Pertussis toxin-catalyzed [32P]ADP-ribosylation of Gi alpha was significantly reduced by 100 microM GTP gamma S (78.4 +/- 3.6% of control), by 100 mM NaF (41.9 +/- 9.1% of control), and by carbachol (100 microM) (29.2 +/- 9.0% of control). Atropine (10 microM) inhibited the carbachol effect by greater than 90%, suggesting that the muscarinic receptors were functionally coupled to Gi proteins. beta-Adrenergic agonists increased adenylyl cyclase activity, but muscarinic agonists failed to inhibit this enzyme. In summary, guinea pig tracheal epithelial membranes contain muscarinic receptors, Gi alpha (2) and adenylyl cyclase, which are appropriately coupled.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8003345 TI - [Chromosomal aberrations, sister chromatid exchanges and micronuclei induced in human lymphocytes by sodium bisulfite (sulfur dioxide)]. AB - The frequencies of chromosomal aberrations (CA), sister chromatid exchanges (SCE) and micronuclei (MN) in human blood lymphocytes exposed to sodium bisulfite (sulfur dioxide) at varies concentrations ranging from 5 x 10(-5) to 2 x 10(-3) mol/L in vitro were studied. It was shown that sodium bisulfite (NaHSO3 and Na2SO3, 1:3 mol/L) caused an increase in SCE and MN of human blood lymphocytes in a dose-dependent manner, and also induced mitotic delays and decreased mitotic index of the lymphocytes. For CA, our results indicated that sodium bisulfite induced an increase of chromatid-type aberrations of the lymphocytes from three of four donors in a dose-dependent manner. The chemical at low concentrations induced chromatid-type aberrations but not chromosome-type aberrations; at high concentrations induced-both chromatid and chromosome-type aberrations of lymphocytes. No cytogenetic effects of sodium bisulfite on the human blood lymphocytes were observed in these assays. The results have confirmed that sulfur dioxide is a clastogenic and genotoxic agent. PMID- 8003344 TI - Iron enhances uptake of mineral particles and increases lipid peroxidation in tracheal epithelial cells. AB - The factors that determine whether an exogenous mineral particle will be taken up by tracheobronchial epithelial cells are unclear. We have previously proposed that active oxygen species play a role in this process, most likely through iron catalyzed formation of hydroxyl radical and subsequent lipid peroxidation of cell membranes. To further examine this hypothesis, we prepared rat tracheal explant cultures and exposed them for 1 h to suspensions of amosite asbestos or titanium dioxide (rutile) that had been preincubated with varying concentrations of a mixture of ferrous and ferric chloride. Explants were then maintained in organ culture in air/CO2 for 1 wk to allow particle or fiber uptake to occur. Particles or fibers in the tracheal epithelium were determined by light microscopic morphometry. Similarly treated explants were assayed for malondialdehyde as a measure of lipid peroxidation in the epithelial cells. Asbestos fibers without added iron caused lipid peroxidation, but this was not true of titanium dioxide particles. For both types of dust, increasing adsorbed iron concentrations were associated with increasing particle uptake and increasing lipid peroxidation. These observations suggest that cationic iron may play a major role in particle uptake by tracheobronchial epithelia, and that particle uptake is also related to iron-mediated lipid peroxidation. PMID- 8003346 TI - [Evaluation and extension of Markov process models for the evolution of DNA]. AB - Markov process models of nucleotide substitution are evaluated. A model proposed by Lanave et al (1984), alleged to need no priori assumption about the substitution pattern, is found to have the assumption of reversibility. Calculations based on the 2-p, 4-p, and 6-p substitution schemes show that site variation of substitution speed leads to serious under-estimation of sequence divergence by various methods. Spatial pattern variation also leads to under estimation, but the discrepancy is slight. A nonhomogeneous Markov process model is used to study the temporal variations of rates and it is shown that the estimated number of substitutions reflects a rate averaged over time. The implications of those results to evolutionary phylogenetics are discussed. PMID- 8003347 TI - [Studies of the miotic chromosomes, meiosis and spermatogenesis of a macaque hybrid]. AB - The mitotic and meiotic chromosomes, as well as the spermatogenesis of a male hybrid between Macaca fascicularis and M. assamensis have been studied using chromosome banding, microspreading, and tissue sectioning techniques. The band patterns of the parental chromosome complements are found highly homologous. The observation on meiosis and testis histology indicates that the hybrid should be fertile. It is suggested that the reproductive barrier between M. fascicularis and M. assamensis is not complete and may resulted from ecological isolation. The taxonomic status of M. fascicularis and M. assamensis is discussed also. PMID- 8003348 TI - [Cloning and DNA sequencing of the gene encoding trichosanthin]. AB - A gene encoding Trichosanthin (TCS) was amplified by means of DNA polymerase chain reaction (PCR) and cloned from the genomic DNA of Trichosanthes kirilowii. Its DNA sequence has been determined. Nucleotide sequence analysis indicates that the cloned TCS gene includes 5'-flanking region and the encoding sequence for TCS preproprotein. Comparison of its encoding sequence with the published nucleotide sequences of three TCS genes demonstrates that they have the sequence homologies of 99.20%, 98.74% and 98.64% respectively. Comparing its deduced amino acid sequence with four reported amino acid sequences of TCS demonstrates that they have the sequence homologies of 98.62%, 97.62%, 97.41% and 98.38% respectively. A new TATA-like box sequence was found in the 5'-flanking region of cloned TCS gene. In order to further study the structure, expression, regulating mechanism of TCS gene and the structure-functional relationship of TCS, a series of mutants of TCS gene has been constructed. The expression of these mutants in bacteria and transgenic plant has being studied. PMID- 8003349 TI - [mtDNA polymorphism and differentiation of subspecies of Chinese raccoon dog (Nyctereutes procyonides)]. AB - The mtDNA from 14 Raccoon dogs of 7 geographical populations was analyzed with 8 restriction endonucleases, and the restriction map was constructed. Furthermore, UPG molecular phylogenetic trees of the mtDNA were constructed based on the genetic distances. Our results indicated that the differentiation was obvious within geographical populations of the subspecies N. p. procyonoides, and that the event of divergence in Chinese Raccoon dog first occurred between the southern and northern populations, and then, between the western and the eastern populations. We proposed that both of the Huabei and Shanxi populations which had not been identified could be classified into two independent subspecies respectively. PMID- 8003350 TI - The phenomenon of dysautonomia and mitral valve prolapse. AB - In recent years research has shown that subsets of patients with mitral valve prolapse also have associated autonomic or neuroendocrine dysfunction that can result in a number of related symptoms, including fatigue, palpitations, chest pain, exercise intolerance, dyspnea, dizziness, headache, sleep disorders, gastrointestinal disturbances, cold extremities, and panic attacks. These patients have been classified as having mitral valve prolapse syndrome. This article discusses the pathogenesis and management of mitral valve prolapse syndrome and serves to make clinicians aware of newer developments in the study of autonomic function and dysfunction. PMID- 8003351 TI - Application of control chart statistics to blood pressure measurement variability in the primary care setting. AB - This study was undertaken as an interdisciplinary effort in response to a frequently frustrating clinical problem of interpreting variable blood pressure measurements under uncertain conditions of quality control. The method is an application of the Shewhart Control Chart analysis to blood pressure measurement in adults in an academic nursing center. The natural variability found in a series of blood pressure readings is measured and described after a pilot study to eliminate examiner, equipment, and time interval variability. Results revealed that there was a significant drop from the first systolic reading to subsequent readings. A three standard deviation limit will be met if the range between the second and third systolic reading does not exceed 13 and the range between the second and third diastolic readings does not exceed 11. Thus for recognition and management of measurement variability, three blood pressure measurements 1 minute apart should be taken as a routine, and the average of the second and third reading recorded. The positive impact on clients, providers, and interdisciplinary research colleagues in changing measurement technique to achieve greater quality in clinical practice is discussed. Limitations and recommendations are presented. PMID- 8003352 TI - Toward Healthy People 2000: the role of the nurse practitioner and health promotion. AB - The central purpose of Healthy People 2000 is to increase the proportion of Americans who live long and healthy lives. The best health promotion strategies are those related to individual lifestyle, and include personal choices made in a social context that have a significant influence over one's health. The primary lifestyle activities include: physical activity; nutrition; alcohol, tobacco, and other drug use; family planning; and violent and abusive behavior. Nurse practitioners play a significant role in promoting healthy lifestyle behaviors in their patients. This article presents an innovative teaching strategy used to teach health promotion concepts and intervention strategies to nurse practitioner students. The course design follows a clinical protocol format, which facilitates translation to clinical practice. PMID- 8003353 TI - Injuries to the anterior and posterior cruciate ligaments of the knee. PMID- 8003354 TI - Reflections and directions from the president of the American Academy of Nurse Practitioners. PMID- 8003355 TI - The American Academy of Nurse Practitioners. National Health Care Reform position paper. PMID- 8003356 TI - Legal approaches to the restraint of trade of nurse practitioners: disparate reimbursement patterns. AB - Nurse practitioners (NPs) can face, and have faced, several challenges in the health care environment. As with the denial of hospital admitting or staff privileges, the granting of inequitable reimbursement levels by state administrative bodies, physicians, insurers, and other members of the health care community may limit NP practice. Several strategies are discussed that will demonstrate how nurse practitioners can use legal and administrative mechanisms (e.g., antitrust laws) to eliminate restraints of trade and assure the availability of more equitable direct reimbursement patterns. PMID- 8003358 TI - Running injuries. PMID- 8003357 TI - The role of the nurse practitioner in promoting sexuality in the institutionalized elderly. AB - This article examines sexuality in the institutionalized elderly. It also reviews current research on nursing home staff members and their perceptions of sexuality in nursing homes. Interventions by the nurse practitioner to promote sexuality in nursing homes are explored. Recommendations for future research are discussed. PMID- 8003359 TI - Factors that prevent women of low socioeconomic status from seeking prenatal care. AB - While there is an international trend toward lowering infant mortality, the United States ranks 19th among industrialized nations. In Arizona, as across the nation, a large and increasing number of low birth weight (LBW) infants are being delivered. This number is viewed with alarm as LBW is associated with infant mortality; however, LBW may be preventable in many cases if mothers receive adequate prenatal care. Despite recognition that absent or inadequate prenatal care is an important risk factor, a large number of women deliver without such care. In Arizona, the percentage of women delivering at a large metropolitan public hospital without prenatal care doubled in a 2-year period, reaching 14% (764 women). The majority of these women were of low socioeconomic status. The purpose of this study was to explore the reasons given by women delivering at this hospital for not seeking prenatal care. It was determined that a qualitative methodology was most appropriate; thus, an interview guide was developed with both demographic and open-ended probing questions. Fifteen respondents--5 Caucasian, 8 Latino (5 Spanish-speaking only), 1 Afro-American, and 1 Native American--participated in the interviews. The data were transcribed from taped interviews and studied using content analysis. Eleven barriers were identified and sorted into two categories: internal and external. Internal barriers identified by the women were attitudes associated with low motivation, knowledge deficits, fear, and fatigue. External barriers elicited were finances, transportation, system difficulties, lack of support, lack of child care, missed work, and insufficient time.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8003360 TI - Nurse practitioners: need for and willingness to hire as viewed by nurse administrators, nurse practitioners, and physicians. AB - The problem investigated in this project was the identification of need for and desire to hire nurse practitioners in a rural western state. Participants included licensed nurse practitioners, nurse administrators of licensed agencies, and licensed physicians in the state of Nevada. The survey examined the participant groups' views of the need for and their desire to hire nurse practitioners. The findings showed differences among the groups in relation to their education levels and whether they were practicing in rural or urban areas. The most pronounced finding was the indicated need for more information related to the role and functions of nurse practitioners before hiring them. Recommendations for future study are also included. PMID- 8003361 TI - Managed outcomes: a strategy to improve the nation's health. AB - Current health care delivery systems in the United States have led to high cost, uneven quality, less than universal coverage, undue emphasis on a medical/clinical model, and scant attention to primary care and prevention. In the context of health care reform, a new strategy is introduced that reverses present trends and incentives, called managed outcomes. This strategy is not specific to any particular health care delivery system. Managed outcomes encourages experimentation and flexibility in the design of health care systems and fosters primary care, health promotion, and disease prevention models. It links purchasing decisions to established specific and measurable goals that can provide quality and cost-effective services to improve health. PMID- 8003363 TI - Dr. Marla Salmon, director, Division of Nursing U.S. Department of Health and Human Services. Interview by Carole Jennings. PMID- 8003362 TI - Achilles injuries. PMID- 8003365 TI - Sleep problems in the elderly. AB - Sleep problems in older adults are so common that nearly half of all hypnotic prescriptions written are for persons over 65 years old. Although normal aging affects sleep, the practitioner should evaluate the many factors that cause insomnia: medical illness, psychiatric illness, dementia, alcohol and/or polypharmacy, restless legs syndrome, periodic leg movements, and sleep apnea syndrome. Nonpharmacologic treatment of sleep disorders is preferred. The nurse practitioner can assess and manage elderly patients with sleep disorders, but they need to refer those who can benefit from evaluation to a sleep disorder center. PMID- 8003364 TI - Sources of stress for nurse practitioners. AB - The purpose of this study was to identify perceived stressors and manifestations of stress in nurse practitioners practicing in Missouri and California. The greatest sources of stress reported by the entire sample (N = 80) were in the categories of time demands and role restrictions. Missouri nurse practitioners found role restriction problems significantly more stressful than California nurse practitioners did. Manifestations of stress fell within the norms of non psychiatric adults on the Symptom Check List 90-R. PMID- 8003366 TI - Neurogenic claudication. PMID- 8003367 TI - Hantavirus. PMID- 8003368 TI - Rational-emotive therapy in the management of migraine headache. AB - Traditional treatments have drawbacks and are not fully effective for all patients suffering from migraine headaches. Rational-emotive therapy (RET) may prove beneficial as a complementary treatment to medication and biofeedback in the management of chronic migraine headache. This article explains RET and provides a rationale for its use in migraine therapy. A case study illustrates RET in action. Research studies of RET with migraine patients are discussed. PMID- 8003369 TI - Practical knowledge and competencies of the healing role of the nurse practitioner. AB - This qualitative study describes the practical knowledge and competencies of the healing role of the nurse practitioner. The conceptual framework is based on Benner's (1984) domains of nursing practice and aspects of practical knowledge and Brykczynski's (1985) study of the clinical practice of nurse practitioners. The healing role is described within the context of the healing domain of the National Organization of Nurse Practitioner Faculties' curriculum guidelines (Zimmer et al., 1990) and Benner's aspects of practical knowledge. The study used the interpretive research approach of Heideggerian hermeneutic phenomenology. The findings contribute two maxims that constitute aspects of practical knowledge: "little things mean a lot" and "healing begins with listening," and two additional healing competencies: sensitive humor and risk taking. PMID- 8003370 TI - Shin splints. PMID- 8003372 TI - Resources to put more prevention into your practice. PMID- 8003371 TI - New and developing methods of contraception. PMID- 8003373 TI - Congestive heart failure: early recognition of congestive heart failure in the primary care setting. AB - Approximately 400,000 patients in the United States are newly diagnosed with congestive heart failure each year. The vast majority of these patients will not survive 5 years. Symptoms that indicate a decline in patient status often go unrecognized by providers. Early identification of insidious changes and prompt intervention can improve cardiac function and decrease the incidence of acute episodes and repeated hospitalizations. Nurse practitioners in the primary care setting are often called upon to manage these patients. By understanding the physiological changes as they occur and the underlying etiology, management is enhanced. PMID- 8003374 TI - Problems of the shoulder. PMID- 8003375 TI - Choosing an antibiotic. PMID- 8003376 TI - Opportunities and challenges: strategies for implementing multidisciplinary documentation forms. PMID- 8003378 TI - The critical care technician program: four years later! PMID- 8003377 TI - Quality outcomes for case manager practice. PMID- 8003379 TI - Analysis of the intermolecular contacts within sickle hemoglobin fibers: effect of site-specific substitutions, fiber pitch, and double-strand disorder. AB - An atomic model of the sickle hemoglobin (HbS) fiber was synthesized by combining the molecular coordinates of the fiber (obtained from electron microscopy) with atomic coordinates of the sickle hemoglobin double strand (obtained from X-ray crystallography). The model is stereochemically acceptable. The majority of polymerization-sensitive HbS mutants are located at fiber contact sites and the majority of the mutants that do not affect polymerization are not located at contact sites. The residues at intermolecular contacts in the fiber model are reported. We have searched the coordinate space in the vicinity of the EM reconstructions to find models with alternative sets of coordinates that satisfy the mutant data, contain 5-A contacts between double strands, and are stereochemically acceptable. This involved a systematic examination over 297 different models. The alternative fiber models were generated with a range of fiber pitch, double-strand positions, and double-strand polarity. Models which had unacceptably close contacts between atoms, failed to satisfy the mutant data, or did not have 5-A contacts between double strands were considered unacceptable. None of the acceptable alternative fiber models improved the agreement between the polymerization behavior of HbS mutants and their contact site location. However, several models could account for the polymerization data equally well. Residue locations for single-site HbS mutations that could discriminate between alternative fiber models are proposed. The twist of HbS fibers varies in an apparent random manner with an average rotation of 7.8 +/- 2.5 degrees per molecule and a maximum rotation of 16 degrees per molecule. The number of interdouble-strand contacts as a function of fiber twist shows a broad maximum around 9 degrees and may account for the observed range of fiber pitch. This study shows that the upper limit on the fiber twist could result from a loss of axial contacts and repulsive van der Waals interactions between residues involved in interstrand contacts. The loss of axial contacts limits the radial growth of the fiber. In the appendix we analyze the methodology used by I. Cretegny and S. J. Edelstein [(1993) J. Mol. Biol. 230, 733-738] to build a model of the fiber. Our examination reveals shortcomings in the methodology of Cretegny and Edelstein. One result of these shortcomings is that the model synthesized by Cretegny and Edelstein is not stereochemically acceptable because it gives rise to a large number of excessively close (less than 1.4 A) atom-atom contacts, suggesting interpenetration of the molecular envelopes. PMID- 8003380 TI - Tubulin conformation in zinc-induced sheets and macrotubes. AB - The protein tubulin is the main constituent of microtubules. Previous studies have shown that zinc ions induce the formation of crystalline sheets and macrotubes of tubulin. Both crystal types are suitable for structural studies by electron crystallography. However, crystallographic structural analysis of tubulin has been hampered by limited crystal size and quality and the inability to control crystal polymorphism. We can obtain well-ordered crystals which are grown upon prolonged incubations (up to 24 hr). The presence of NaCl delays the degradation of the crystals, and addition of the protease inhibitor pepstatin improves crystal quality. The crystal form (sheet or macrotube) can be controlled with incubation conditions. The size of the crystals can reach up to 2 microns in width for the sheets and up to 0.5 microns in diameter for the macrotubes. Both crystal types can reach several micrometers in length. Comparison of the projection maps of the two crystal structures shows that adjacent protofilaments in the macrotubes are shifted by about 6 A relative to their positions in the sheets. Observable changes of monomer shape appear to allow close interprotofilament contacts to be maintained in both crystal forms. Images of glucose-embedded specimens obtained under these conditions give structural information beyond 4 A resolution. Merging of high- and low-resolution data allows for unambiguous assignment of monomer boundaries to high-resolution features. PMID- 8003381 TI - Molecular characterization of the "26S" proteasome complex from rat liver. AB - The molecular properties of an ATP/ubiquitin-dependent "26S" proteasome complex purified from rat liver were examined by physicochemical, biochemical, and morphological analyses. On ultracentrifugation, the proteasome complex sedimented as almost a single component with a sedimentation coefficient of 30.3S. Dynamic light-scattering measurements indicated that it has a diffusion coefficient of 1.38 x 10(-7) cm2/sec and a Stokes radius of 15.5 nm. From these two coefficients, the protein complex was estimated to have the high molecular weight of 2.02 x 10(6). Static light-scattering analysis indicated a molecular weight of 1.91 x 10(6) and a radius of gyration of 16.8 nm. The proteasome complex was found to be composed of multiple subunits of the 20S proteasome with molecular weights of 2.1-3.1 x 10(4) and 15-20 protein species with molecular weights of 3.5-11.0 x 10(4), which were directly associated with the 20S proteasome. The electron micrographic finding that the 26S proteasome complex had a caterpillar shape, direct electronmicroscopic observations on the subunit arrangement of the 20S proteasome, and classification of the subunits of the latter into two groups with respect to sequence homology suggested that the 26S complex is a symmetrical assembly of two domains, each containing a large terminal subset and half the central 20S subset of components. For clarification of the molecular structure of the 26S proteasome complex in solution, its physicochemical parameters were calculated theoretically using a model based on this caterpillar-shaped complex. The values obtained for the Stokes radius and radius of gyration of 12.2 and 14.9 nm were consistent with the experimental values. These results provide evidence that the 26S proteasome complex is a cylindrical caterpillar-like structure of "30S" in solution, consisting of a 20S proteasome component with proteolytic function and multiple other components, which possibly have regulatory roles. PMID- 8003382 TI - Direct in situ structural analysis of recombinant outer membrane porins expressed in an OmpA-deficient mutant Escherichia coli strain. AB - An OmpA-deficient mutant of an OmpF/OmpC-free Escherichia coli B strain was selected using phage K3. The mutant strain was characterized by SDS-gel electrophoresis, immunoblotting, and electron microscopy. All major outer membrane proteins, including OmpA, were absent. This strain was then transformed with the plasmid pMY222 encoding the K12 OmpF porin or with pBlue-script-derived plasmids, encoding the porins OmpC, PhoE, and maltoporin, respectively. Following SDS extraction of outer membrane sacculi from strains expressing individual porins, crystalline porin arrays that allowed in situ structural analysis to be performed were observed. Furthermore, the absence of endogenous major outer membrane proteins facilitated the purification of native porin-lipopolysaccharide complexes, the functionally active channels, from the sacculi of transformed strains. PMID- 8003383 TI - The effects of radiation damage on the structure of frozen hydrated HSV-1 capsids. AB - Radiation damage imposes stringent limits on the information content of electron micrographs of biological specimens. In this study, we have investigated its effects on frozen, hydrated specimens and three-dimensional reconstructions calculated from cryomicrographs using capsids of herpes simplex virus as a model system. Multiple-exposure series of micrographs of both B-capsids (which contain no DNA) and C-capsids (which are fully packaged) were recorded and reconstructions were calculated from the first exposures, corresponding to a cumulative electron dose of 6-7 e-/A2, and from later exposures (25-40 e-/A2). Experimental procedures were standardized to ensure that perceived changes in the micrographs and reconstructions would be attributable to radiation damage alone. The effects of the higher doses in both the micrographs and the reconstructions were expressed as a progressive blurring of the finer details, corresponding to a delocalization of structure in the ice-embedded specimens. The resolutions of the reconstructions were quantified according to a form of the Fourier ring correlation coefficient criterion, according to which the first-exposure reconstructions had resolutions of 30-36 A. The fifth-exposure B-capsid reconstruction had comparable nominal resolution, although it exhibited progressively lower correlations at higher spatial frequencies. Qualitatively similar changes in the series of C-capsid reconstructions were observed although they were more pronounced, presumably because these micrographs had lower contrast and signal-to-noise ratios. We infer that the observed changes in the images and reconstructions and the concomitant loss in contrast in the immediate vicinity of the capsid surface may reflect radiation-induced perturbation of molecular structure and/or the release of peptide fragments. Nevertheless, the observed changes are relatively subtle, at least at the operational resolution of this study; overall, our results support earlier indications (M. F. Schmid et al. J. Struct. Biol. 108, 62-68, 1992) that prospects are quite good for tilt-series reconstructions from cryoelectron micrographs, including six to eight views of the same specimen. PMID- 8003384 TI - Three-dimensional immunoelectron microscopy of scorpion hemocyanin labeled with a monoclonal Fab fragment. AB - An immunocomplex of the 4 x 6-meric hemocyanin of the scorpion Androctonus australis with the monoclonal Fab fragment L104 was reconstructed from electron micrographs of a negatively stained specimen, using the double-carbon-layer technique. The resulting structure enables a clear visualization of the Fab fragments bound to the four copies of the Aa6 subunit and directly confirms a previous localization of the L104 epitope deduced from two-dimensional image processing. Despite a strong flattening effect produced by the negative-staining technique the orientations of the Fab fragments are well characterized. Moreover, the observation of a central hole within the elbow bends of the Fab fragments provides information about the disposition of the Fabs around their main axis. PMID- 8003385 TI - [Emergent pathologies: Rhodococcus equi infection in the acquired immunodeficiency syndrome]. AB - Rhodococcus equi is an intracellular facultative, gram-positive, partially acid fast, cocco-bacillary microorganism of increasing importance as a pathogen in severely immunocompromised HIV-positive patients. Rhodococcus equi may cause invasive pulmonary infection, bacteremia and disseminated infection. Rhodococcus equi is easily cultured from blood or sputum on standard media, but is frequently regarded as a contaminant. Delay in establishing a definite diagnosis may result in a poor outcome in most cases. Treatment in humans is not standardized. Surgical intervention may be beneficial in selected cases. PMID- 8003386 TI - Frequency and clinical significance of anti-RNP antibodies in Italian SLE patients. AB - The frequency and clinical significance of anti-RNP antibodies in patients with systemic lupus erythematosus (SLE) are still a matter of debate. In this study we report our experience with a series of 123 unselected Italian patients (93 adults and 30 children) suffering from SLE according to the ARA criteria. Anti-RNP were detected by counterimmunoelectrophoresis in 25 patients (20%), 19 of whom did not show other antibodies to extractable antigens (isolated RNP). Our study shows a striking association between anti-RNP and arthritis as well as between anti-RNP and Raynaud's phenomenon. In addition, we found an association between anti-RNP and lack of renal involvement. This association was limited to those patients with isolated RNP and was independent of the presence of anti-dsDNA antibodies. These data were confirmed by a 50 month follow-up study. PMID- 8003387 TI - Pro-thrombotic states and their diagnosis. AB - The authors define pro-thrombotic states as conditions associated with a high frequency of thrombosis; this association is based on pathogenetic or simply clinical and epidemiological relationships. Thrombophilic states have well defined, specific causes: antithrombin III, protein C and S and similar deficiencies for inherited thrombophilias, and lupus anticoagulant, antiphospholipid antibodies for the acquired forms. Another identifiable group is made up of several conditions predisposing to thrombosis (CPT) characterized by less specific and multiple mechanisms (e.g. malignancy, inflammatory bowel disease, nephrotic syndrome, diabetes, obesity, etc.). These conditions may induce thrombosis by themselves or contribute to its clinical onset in patients with true thrombophilic states. This is especially the case for patients who are taking contraceptive drugs, are pregnant, have undergone surgery or trauma. The term hypercoagulability states is by no means equivalent to either thrombophilia or CPT. In fact, hypercoagulability may be defined as "activation of blood coagulation" in the presence of specific markers such as fibrinopeptide A and prothrombin fragment F1 + 2. Hypercoagulability is therefore a laboratory rather than a clinical condition and can be a transient feature appearing during certain phases of thrombophilia or CPT. Lastly, conditions involving the presence of hemostatic risk factors for atherothrombosis are simply terms used to describe a statistical-epidemiological relationship between certain hemostatic variables (fibrinogen, factor VII, PAI, etc.) involving the risk of cardiovascular morbidity and mortality but not necessarily indicating a hypercoagulability state. PMID- 8003388 TI - The syndrome of idiopathic CD4+ lymphocytopenia. AB - The syndrome of idiopathic CD4+ lymphocytopenia has recently been recognized and referred to as the persistent depletion of peripheral blood CD4+ T lymphocytes below 300 cells per cubic millimeter or less than 20% of total lymphocytes in the absence of either HIV infection or other known causes of immunodeficiency. The available literature indicates that neither human retroviruses (HIV-1, HIV-2, HTLV-I, HTLV-II) nor other transmissible agents play any clear-cut role in the pathogenesis. Furthermore, the epidemiologic, immunologic and clinical features of this syndrome differ substantially from those of HIV infection. The heterogeneity of both immunologic abnormalities, in addition to CD4+ depletion, and clinical course in patients with this disorder points out no common cause although in at least a subset of patients the pathogenetic pathways could be shared with common variable immunodeficiency. PMID- 8003389 TI - Obesity and cardiovascular diseases. AB - Obesity and overweight have great clinical and social significance and are associated with a number of medical and surgical complications. We attempt here to summarize current knowledge on the subject and describe the research we are presently carrying out in this field. After a brief introduction, definition, and discussion of etiopathogenesis, the indexes of ponderal excess and epidemiology are illustrated. The cardiovascular adjustments and the relationships between obesity and hypertension, ischemic heart disease and congestive heart failure are then treated. One aim of our investigation was to study the modifications of an entire set of biological and clinical parameters which could concretely formulate and/or identify some pathophysiological links between obesity and heart disease. We thus studied obese subjects with hypertension, diabetes and multiple cardiovascular risk factors. We also studied a group of asymptomatic obese subjects, whom we define as "the healthy obese". Our results, supported by the medical literature, led to the conclusion that obesity is an important and/or independent cardiovascular risk factor. We think, however, that it would be prudent to await for the results of interventional trials and follow-up studies involving a large number of young, healthy obese subjects in order to monitor the most important biological variables over the long term. PMID- 8003390 TI - [Hyperparathyroidism due to parathyroid carcinoma located in the mediastinum]. AB - Parathyroid gland carcinoma is a rare cause of primary hyperparathyroidism. The authors discuss the case of a 56-year-old man who presented with hypercalcemia and multiple bone lesions suggestive of tumor metastases. Laboratory and radiological investigations revealed primary hyperparathyroidism in a patient with evidence of osteitis fibrosa cystica, sustained by carcinoma of a mediastinal parathyroid gland. Early titration of parathyroid hormone (PTH) levels in all patients with hypercalcemia of unclear cause is important for early diagnosis of cases that are tumor-sustained and prevention of the most severe complications. The role of immunostaining with anti-PTH antibodies in demonstrating parathyroid gland tissue in ectopic and/or non-functioning primary tumors, as well as metastases, is also discussed. PMID- 8003391 TI - Treatment of biguanide-induced lactic acidosis: reproposal of the "physiological" approach and review of the literature. AB - We report a case of severe biguanide-induced lactic acidosis which did not respond to symptomatic alkali treatment via either intravenous bicarbonate infusion or bicarbonate-dialysis. We thus initiated a therapeutic strategy based on insulin and thiamine only in order to reactivate the pyruvate oxidative pathway, in which both drugs play important roles as cofactors. This original "physiological" approach proved effective, and further alkali administration was unnecessary. Our results prompted a review of the literature on the treatment of biguanide-induced lactic acidosis, a situation in which the absence of precise therapeutic rules can undoubtedly affect both the evolution and the prognosis of the syndrome. PMID- 8003392 TI - Severe osteomalacia due to gluten-sensitive enteropathy. AB - This report discusses a severe case of osteomalacia due to gluten-sensitive enteropathy: it stresses the clinical features and describes an atypical form of gluten-sensitive enteropathy, in which gastroenterological symptoms were absent. Wasting and osteomalacia causing skeletal deformation with spontaneous fractures were observed in a 31-year-old woman who had marked hypophosphoremia, a tendency to low serum calcium levels and slight multi-deficiency anaemia. The patient was in a state of depression. The causes of osteomalacia and then a general malabsorption syndrome were investigated. Anti-gliadin antibodies were positive. Histological tests on duodenal mucous revealed a pattern indicative of gluten sensitive enteropathy. A gluten-free diet was prescribed and at a check-up one month later the patient had improved markedly. Skeletal symptoms are predominant in 30% of atypical forms of gluten-sensitive enteropathy. The severity of this case was due to a late diagnosis. PMID- 8003393 TI - [Images of man. Medicine and philosophy compared]. PMID- 8003394 TI - Antibody shows promise in treating B-cell lymphoma. PMID- 8003395 TI - Neurologic complications of cytokine therapy. AB - There have been surprisingly few controlled studies of the central nervous system actions of cytokines in humans, although many clinical trials have briefly reported side effects of these drugs. Clinical trials using cytokines have chiefly involved patients with cancer, often at an advanced stage, and prospective formal neurologic assessment has been infrequent. In patients with malignancy, a host of variables can confound neurologic evaluation, including nutritional status, metastatic deposits, metabolic derangements, effects of former treatments, and infection. The effects of the cytokines on the central nervous system are multiple and limit their clinical use. Careful prospective clinical study of these agents is essential and may yield insights into their functions in the CNS and increase their efficacy as clinical tools. PMID- 8003396 TI - Subcutaneous opioid infusions at home. AB - The ability to provide subcutaneous infusions in the home has had a major impact on patient care. The main indication for this approach in the cancer population is the need for prolonged parenteral administration of an opioid drug. Successful administration begins with proactive consideration of patient selection; choice of pump, drug, mode of infusion, and dosing schedule; the resources of the family and community health-care system; and cost and insurance coverage. Long-term management requires ongoing liaison among the hospital pain management team, home care infusion agency, and community physicians and nurses. PMID- 8003397 TI - Malignant neoplasms of the hard palate and upper alveolar ridge. AB - Malignant neoplasms of the hard palate and upper alveolar ridge can arise from the epithelial (mucosal), salivary, hematopoietic, or mesenchymal tissues in this region. Unlike other regions in the head and neck, only about two thirds of malignant neoplasms of the hard palate are squamous cell carcinomas, and few large series have reported treatment protocols and outcomes for patients with these tumors. In this review, we will describe our series of 51 patients with malignant neoplasms of the hard palate and upper alveolar ridge. This review will emphasize the surgical treatment program and rehabilitative techniques developed at the University of Pittsburgh. PMID- 8003399 TI - Clinical trials. Referral resource. Phase II Ovarian Cancer Trials. PMID- 8003398 TI - Quality of life, appetite, and weight change in patients receiving dose-intensive chemotherapy. AB - Quality of life was assessed by self-report questionnaires in 30 patients receiving dose-intensive chemotherapy for either non-small-cell lung cancer (20 patients) or recurrent head and neck cancer (10 patients). Megestrol acetate was given daily to try to improve appetite and prevent the weight loss usually associated with this chemotherapy. Appetite did not change significantly overall during the first 4 weeks of chemotherapy, but it did improve in those patients still receiving chemotherapy at 8 weeks. Changes in global quality of life were significantly correlated with changes in appetite, fatigue, energy level, and physical function. Thus, these parameters may have more relevance to patients' perceptions of quality of life than does weight change, and should be used more frequently as endpoints in studies of supportive care and palliative treatment of patients with cancer. PMID- 8003401 TI - Boron neutron capture--an investigational cancer treatment modality. PMID- 8003400 TI - Chemoembolization of hepatic malignancies. AB - Chemoembolization has several theoretical advantages over intravenous or intraarterial infusion therapy for treatment of primary or metastatic liver tumors. This technique delivers highly concentrated drugs to the tumor, then arrests blood flow. This renders the tumor ischemic, while achieving a drug concentration in the tumor 10 to 25 times greater than can be achieved by infusion. The dwell time for the drug is markedly prolonged, with measurable drug levels present in tumor as long as a month after chemoembolization. Up to 85% of the administered drug is trapped in the liver, minimizing systemic toxicity. Worldwide experience has established chemoembolization as the treatment of choice for unresectable hepatoma. Metastatic lesions from ocular melanoma, neuroendocrine tumors, and sarcomas have been reported to respond well to chemoembolization. The technique also shows promise against colorectal metastases. PMID- 8003403 TI - Expanded programme on immunization. Programme review. PMID- 8003402 TI - Dengue fever. Outbreak of classic dengue. PMID- 8003404 TI - Expanded programme on immunization (EPI). Poliomyelitis outbreak. PMID- 8003405 TI - Cancer. Mortality trends for selected smoking-related cancers and breast cancer, 1950-1990. PMID- 8003406 TI - Japanese encephalitis. Inactivated Japanese encephalitis virus vaccine. PMID- 8003408 TI - New drug for exposure to HIV goes on trial. PMID- 8003407 TI - A comprehensive central register of more than 700 HIV/AIDS initiatives. PMID- 8003410 TI - Breaking new ground. PMID- 8003409 TI - Beyond the Clothier inquiry. PMID- 8003412 TI - Infection control: understanding the nature of bacteria. PMID- 8003411 TI - Orthopaedics: patient assessment before surgery. AB - The potential for pre-admission assessment clinics has been discussed for many years, but only recently have such clinics been developed. This article reviews how one clinic was conceived and developed. The perceived benefits included improved patient care, opportunity for informed choice, reduction in patient cancellation rates and improved utilisation of theatre time. PMID- 8003413 TI - A waste of space or providers of quality care? PMID- 8003414 TI - Working abroad: culture shock. PMID- 8003415 TI - AIDS focus. The second decade in South East Asia. PMID- 8003416 TI - AIDS focus. Developing staff support. PMID- 8003417 TI - AIDS focus. Training for the front line. PMID- 8003418 TI - Team-playing (continuing education credit). PMID- 8003419 TI - The Nat Health files. Bert's package. PMID- 8003420 TI - Coaching and mentoring (continuing education credit). PMID- 8003421 TI - Nursing management. An agenda for nurse leaders. Interview by John Naish. PMID- 8003422 TI - Accident and emergency: primary movers. PMID- 8003423 TI - Europe: women in the Union. PMID- 8003424 TI - Privacy of clients: tags and television. AB - The use of closed circuit television or electronic tagging to monitor patients and clients has become a widely debated issue in the health service. The question to be considered is whether this is an unwarranted invasion of people's privacy or an acceptable way of reducing the risk of an accident occurring? PMID- 8003426 TI - Infection control in high-risk environments. PMID- 8003425 TI - Continence advisers' role in education. AB - This article identifies the factors which contribute towards an effective training and educational role for continence advisers and those which militate against it. It concludes that although the effectiveness of different approaches to training and education on continence issues has not been formally evaluated, continence advisers are strategically placed to perform this function. PMID- 8003427 TI - An educational support group. AB - This article describes an educational support group (ESG) for a cohort of RMN student nurses and two of their teachers. The group, which ran for about one year, had a double task. Its educational task was for members to learn experientially about group theory and practice. The other task was for the group to provide support for members in their educational endeavours generally. Evaluation during and after the group's term demonstrated that the members had moved through the classical stages of group theory, and had emerged with stronger peer relationships and better communication between students and teachers. PMID- 8003428 TI - Aromatherapy. Working with clients who are HIV positive. PMID- 8003429 TI - Spend, spend, spent. PMID- 8003430 TI - One minute wisdom. It was introductory block during my RMN training. PMID- 8003431 TI - Flexible working: banking your assets. PMID- 8003433 TI - Staff support: monitoring mentoring. PMID- 8003432 TI - Child abuse. No smoke, no fire. PMID- 8003434 TI - Androgen receptor mRNA in the rat ovary and uterus. AB - The distribution of androgen receptor messenger RNA (ARmRNA) in the reproductive tissues of adult rats was examined by Northern blot analysis and in situ hybridization using ARcRNA probes corresponding to the androgen binding domain of the receptor. About 10-kilobase rat ARmRNA was observed in all tissues examined in the Northern blot analysis. The amount of ARmRNA in the ovary, uterus and testis was less than that in the prostate. In the in situ hybridization study, extensive labeling was observed in the theca cells of the ovary (proestrous) and the endometrium and endometrial glands of the uterus (proestrous). Moderate labeling was observed in the granulosa cells and stromal cells of the ovary and in the myometrium of the uterus. These results were largely in agreement with the distribution of AR previously reported by ligand binding studies. This present in situ hybridization study may provide a useful tool for the analysis of the regional regulation of AR synthesis in the rat female reproductive tissues. PMID- 8003435 TI - Metabolic profiles of steroids in urine of alcoholics after withdrawal. AB - The metabolic profiles of steroids in urine were analyzed in 13 male alcoholics during long-term abstinence, in most cases exceeding 3 months. The ratios of 5 beta- to 5 alpha-reduced steroid metabolites (etiocholanolone/androsterone and tetrahydrocortisol/allotetrahydrocortisol) were initially elevated but decreased slowly following withdrawal. The half-life of this normalization exceeded 3 weeks. The change was most marked in patients with signs of liver injury, and may reflect a relative decrease of the activity of hepatic 5 alpha-reductase. The ratio between cortisol metabolites carrying a 11 beta-hydroxy and an 11-oxo group was elevated in the patients and showed no tendency to normalize. This might reflect a decrease in the peripheral inactivation of cortisol. PMID- 8003436 TI - Synthesis of (17 alpha,20E/Z)iodovinyl testosterone and 19-nortestosterone derivatives as potential radioligands for androgen and progesterone receptors. AB - To develop androgen and progesterone receptor-based radioligands for SPECT imaging we synthesized several radioiodinated 17 alpha-iodovinyl testosterone and 19-nortestosterone analogs and evaluated their biological properties. The synthesis of these compounds proceeds via the (17 alpha,20E/Z)stannyl intermediates and involves addition of tri-n-butyltin hydride to the 17 alpha ethynyl group of the steroid using either azobisiso butyronitrile or triethylborane as a catalyst. The stannyl derivatives are stereospecifically converted to the corresponding (17 alpha,20E/Z)iodovinyl derivatives using molecular iodine, or to the [125I]iodovinyl analogs using [125I]NaI and H2O2. Androgen and progesterone receptor (AR and PgR) binding affinities were measured via a competitive in vitro binding assay. In general 19-nortestosterone derivatives showed higher receptor affinities as compared to the testosterone derivatives. In the latter series the highest PgR binding affinities were observed with the (17 alpha,20Z)iodovinyl-19-nortestosterone (IVNT) (92 vs 100 for R5020) followed by the 7 alpha-methyl analog, whereas the highest AR binding affinity was observed with the 7 alpha-Me-(17 alpha,20Z)IVNT (54 vs 100 for 5 alpha-dihydrotestosterone). These derivatives were also labeled with 125I and evaluated for their in vivo target organ uptake (prostate and estrogen-primed uterus). The highest PgR-mediated target tissue uptake was observed with the (17 alpha,20Z)-[125I]IVNT and its 7 alpha-methyl derivatives whereas only one derivative, the 7 alpha-Me-(17 alpha,20Z)-[125I]IVNT, showed AR-mediated dorsal prostate retention. Although some of the IVNT derivatives have interesting binding properties, the lack of in vivo selectivity does suggest that the 123I labeled analogs are unlikely to be suitable for imaging of AR and PgR-rich tissues. PMID- 8003437 TI - Development of specific bioluminescent in vitro assays for selecting potential antimineralocorticoids. AB - Efficient antimineralocorticoid selection requires a reliable, discriminating and easy assay for monitoring biological activity of not only the specific receptor, but also closely related receptors such as glucocorticoid and progestin. These related activities should be as low as possible to obtain specific antimineralocorticoid compounds. In this paper, we describe two cellular models used for easy and specific measurement of mineralocorticoid and progestin activities. These models involve the induction of firefly luciferase under hormonal control mediated by a chimeric receptor. The first model comprises transiently transfected MCF-7 cells, whereas the second uses stably transfected HeLa cells. Glucocorticoid activity was assayed with the classic tyrosine aminotransferase induction method in HTC cells. Six compounds of a new family of 11 beta-substituted-17-spirolactone steroids were thus studied and compared to control compounds. Five of them showed antimineralocorticoid activity and one was active at a concentration lower than that of mespirenone. PMID- 8003438 TI - Binding of the anti-inflammatory steroid deflazacort to glucocorticoid receptors in brain and peripheral tissues. In vivo and in vitro studies. AB - Deflazacort (DFC) is a heterocyclic glucocorticoid with anti-inflammatory activity but with decreased side effects. In this study, we have evaluated the capacity of DFC and other glucocorticoids to reach the central nervous system (CNS) in vivo by measuring changes of [3H]dexamethasone (DEX) binding to glucocorticoid receptors (GR) in vitro. GR occupation was effected by DEX in the cerebral cortex, hippocampus, pituitary, liver and thymus, with DFC showing a similar profile except for the cerebral cortex. In contrast, corticosterone weakly occupied GR in the thymus, pituitary and hippocampus and methyl prednisolone was active only in peripheral tissues. Furthermore, IC50 for DEX in vitro amounted to 15-17 nM in the hippocampus and liver, whereas IC50 for the active metabolite 21-deacetyl-DFC (21-OH-DFC) was 4 times higher. 21-OH-DFC bound to type II and was absent from type I GR. When tested in equipotent doses based on IC50 analysis, DFC and DEX similarly induced in vivo ornithine decarboxylase activity in hippocampus and liver, although body weight loss after chronic treatment was significantly less for DFC. The results show that DFC distributes on the CNS similarly to DEX, induces ornithine decarboxylase activity but presents less intensive catabolic effects, making it suitable for use as an anti inflammatory steroid during chronic therapeutic regimes. PMID- 8003439 TI - 1-Carbamoylalkyl-2-phenylindoles: relationship between side chain structure and estrogen antagonism. AB - The 2-phenylindole system has proved to be a versatile structure for the design of potent antiestrogens, especially when functional groups have been introduced into the alkyl side chain in position 1. In analogy to steroidal structures such as ICI 164,384 a number of 2-phenylindoles with carbamoylalkyl and aminoalkyl side chains were synthesized. They bind to the calf uterine estrogen receptor with relative binding affinities between 2.1 and 21 (estradiol = 100). The antiestrogenic effect of these compounds was demonstrated by the inhibition of transcriptional activity which was measured in a new luciferase assay with the EREwtc luc as reporter plasmid. The derivative with a methyl-n-propyldodecanamide side chain (4h) antagonized the effect of estradiol (10(-9) M) completely at concentrations of 10(-7) M and higher. As a sensitive model for quantification of estrogenic and antiestrogenic effects in vitro we used HeLa-cells cotransfected both with the reporter plasmid and estrogen receptor expression vectors HEG0 and HE0. In cells transfected with these vectors transcriptional activity was strongly dependent on side chain structure. With mutated receptors we were able to show that this activity was mainly due to TAF-1 whereas TAF-2 remained silent. When we studied the effect of some of the new compounds in vivo using the mouse uterine weight assay, we observed a correlation between transcriptional activity in transfected HeLa cells and estrogenic effects in mice. Two of the 1 carbamoylalkyl-2-phenylindoles (4f, 4h) proved to be "pure" antiestrogens both in vitro and in vivo. In estrogen-sensitive MCF-7 breast cancer cells, they strongly inhibit cellular growth. Some of the IC50-values were close to 10(-8) M. PMID- 8003440 TI - The interaction of cytokines in regulating oestradiol 17 beta-hydroxysteroid dehydrogenase activity in MCF-7 cells. AB - Oestradiol 17 beta-hydroxysteroid dehydrogenase (E2DH) has a pivotal role in the regulation of oestradiol (E2) concentrations in normal and malignant breast tissues. Previous studies have suggested that a number of cytokines can stimulate E2DH activity to increase the conversion of oestrone (E1) to E2. In this investigation we have examined the effect of TNF alpha, interleukin-1 beta (IL-1 beta) and IL-6 on E2DH activity in MCF-7 breast cancer cells. These cytokines may be produced by breast tumours and their presence in conditioned medium (CM) from tumour-derived fibroblasts was also measured to assess their possible contribution to its E2DH stimulatory activity. Treatment of MCF-7 cells with IL-1 beta and TNF alpha (5 ng/ml) significantly increased (P < 0.001) reductive E2DH (red-E2DH, the conversion of E1 to E2) activity. In contrast, IL-6 at a concentration of 100 ng/ml produced little, if any, stimulation of reductive activity. Combinations of all three cytokines acted synergistically to stimulate red-E2DH activity. No cytokine, either alone or in combination, affected oxidative (E2-->E1) activity. Significant concentrations of IL-6 and IL-1 beta were detected in CM, but the stimulation of red-E2DH activity was much greater than that which could be explained by their levels alone. It is concluded that these cytokines may play an important role in regulating E2DH activity in breast cancer cells and may act synergistically in vivo to enhance the formation of E2 in breast tumours. PMID- 8003441 TI - Biosynthetic pathway of 19-noraldosterone in isolated rat glomerulosa cells. AB - The biosynthetic pathway of 19-noraldosterone (19-noraldo) in isolated rat glomerulosa cells (GC) and fasciculata-reticular cells (FC) was studied by analyzing [14C]pregnenolone metabolism using HPLC and quantification by specific RIA. In GCs, 18,19-dihydroxycorticosterone was detected after 15 min incubation with [14C]pregnenolone, 18-hydroxy-19-norcorticosterone was detected after 30 min and 19-noraldo was detected after 45 min before the appearance of an aldosterone peak. These three mineralocorticoids were not detected in FCs. The results demonstrate that 19-noraldo is synthesized in GCs and then undergoes further metabolism. PMID- 8003442 TI - Inhibition of steroidogenesis by luteal cells of early pregnancy in the rat in response to in vitro administration of a gonadotropin-releasing hormone agonist. AB - Previous studies from this laboratory have demonstrated that the administration of a gonadotropin-releasing hormone agonist (GnRH-Ag) in vivo in early or mid pregnancy to rats induces antifertility effects by suppressing the luteal production of progesterone (P4) within 24h with a concomitant increase in luteal lipid droplets and decreases in the luteal cytochrome P450 side chain cleavage (P450scc) enzyme and its mRNA content. These observations suggest a direct inhibitory effect of GnRH-Ag on the corpus luteum. Here we demonstrate a suppressive effect of GnRH-Ag in vitro on the basal P4, pregnenolone (P5) and 20 alpha-dihydroprogesterone (20 alpha-DHP) production by luteal cells obtained during early pregnancy in rats. We further studied its effect on two key enzymes, namely P450scc and 3 beta-hydroxysteroid dehydrogenase (3 beta-HSD), which participate in the conversion of cholesterol to P5 and conversion of P5 to P4, respectively. We observed that two doses of GnRH-Ag, 10(-4) and 10-7 M, suppress the basal P4 production in vitro after 12 h of incubation by luteal cells; P4 remained suppressed after 48 h of incubation. Basal P5 production was also suppressed after luteal cells were incubated for 12 h with 10(-4) M and 10(-7) M GnRH-Ag, but incubation for 48 h with GnRH-Ag failed to alter P5 production by these cells. 20 alpha-DHP production was suppressed after incubating the luteal cells with both doses of GnRH-Ag for 12 h. GnRH-Ag inhibited P450scc activity after 12 h of incubation and 3 beta-HSD protein content at all time periods measured. These results suggest that GnRH exerts a direct inhibitory effect on luteal steroidogenesis. This inhibition is due to its suppressive effect on P450scc and/or 3 beta-HSD and not due to an increase in P4 metabolites. PMID- 8003443 TI - Inhibition of 11 beta-hydroxysteroid dehydrogenase obtained from guinea pig kidney by furosemide, naringenin and some other compounds. AB - Inhibition of 11 beta-hydroxysteroid dehydrogenase (11 beta-OHSD) can cause excess mineralocorticoid effects and hypokalemia. Several substances causing hypokalemia (glycyrrhizic acid in licorice and gossypol) inhibit this enzyme. We tested other compounds for activity to inhibit 11 beta-OHSD in guinea pig kidney cortex microsomes with NADP as cofactor and cortisol as substrate. Furosemide was an inhibitor while bumetanide was not, indicating a mechanism for the increase K+ excretion caused by furosemide compared with bumetanide. Naringenin (found in grapefruit juice), ethacrynic acid, and chenodeoxycholic acid had inhibitor IC50 values similar to glycyrrhizic acid. We conclude that various compounds can inhibit this enzyme and may play a role in K+ metabolism and adrenocorticosteroid action. PMID- 8003444 TI - Progesterone metabolism by the filamentous fungus Cochliobolus lunatus. AB - Studies of Cochliobolus lunatus m118 steroid metabolism by thin-layer chromatography, mass spectrometry and NMR spectroscopy revealed that the fungus hydroxylates progesterone at positions 7 alpha, 11 beta and 14 alpha, and oxidizes the 11 beta-hydroxy group to the ketone. The 1H NMR spectra of two of the steroid metabolites, 11 beta,14 alpha-dihydroxyprogesterone and 11-oxo-14 alpha-hydroxyprogesterone, are reported for the first time. It is still not known if all the hydroxylation reactions are performed in C. lunatus by a single, non specific, steroid hydroxylase, structurally different from the 11 beta hydroxylase found in higher eucaryotes, or if different forms of the enzyme are involved. PMID- 8003445 TI - Effects of estrogens on human melanocytes in vitro. AB - Subjects with elevated serum estrogen concentrations, such as those who are pregnant or ingesting estrogen-containing contraceptive medication, may develop increased skin pigmentation. As little information is available on the mechanism(s) underlying this relationship, the in vitro effects of estrogens on melanocytes cultured from normal human skin were examined. Physiological concentrations of 17 beta-estradiol (10(-11) to 10(-9) M) significantly increased the activity of tyrosinase in melanocytes from 15 of 23 subjects. The observed increases ranged from 1.2- to 2.4-fold. Melanin synthesis, which correlated with tyrosinase activity (r = 0.98, P < 0.001) was increased to a similar extent. Melanin extrusion was also increased by 17 beta-estradiol (10(-9) M). The estrogens, estriol (10(-9) M) and estrone (10(-9) M) stimulated tyrosinase activity and melanin extrusion to a lesser extent than 17 beta-estradiol. The analogue 17 alpha-estradiol (10(-9) M) was shown to have effects on melanocyte tyrosinase activity and melanin extrusion that were equivalent to those of 17 beta-estradiol. The pure estrogen antagonist ICI 164384 (10(-6) M) also stimulated tyrosinase activity. Cycloheximide (50 micrograms/ml) inhibited 17 beta-estradiol-induced tyrosinase stimulation (P < 0.001). These results indicate that several aspects of melanocyte function respond directly to estrogenic stimulation. The equivalent effects of the 17 alpha-analogue and a "pure" anti estrogen suggest that the 17 beta-estradiol response may be mediated through a non-classical mechanism which is similar to that described in other tissues of neural crest origin. PMID- 8003446 TI - Microbial transformations of steroids--VIII. Transformation of progesterone by whole cells and microsomes of Aspergillus fumigatus. AB - The filamentous fungus, Aspergillus fumigatus, efficiently hydroxylated exogenous progesterone producing, after 3 h of incubation, 11 alpha- and 15 beta hydroxyprogesterone as major products, 7 beta-hydroxyprogesterone as a minor product and trace amounts of 7 beta, 15 beta- and 11 alpha, 15 beta dihydroxyprogesterone. After 72 h the dihydroxyprogesterones were the sole metabolites in the culture medium. Microsomes, prepared by Ca2+ precipitation, catalysed only monohydroxylation of progesterone at the same sites as whole cells. Hydroxylation was dependent on NADPH (but not NADH) which was replaceable by NaIO4. Hydroxylation was inhibited by carbon monoxide and by the azole fungicide, ketoconazole. Microsomes gave a dithionite-reduced, carbon monoxide difference absorbance spectrum with a peak at 448 nm and a Type-I progesterone binding spectrum typical of cytochrome P450 interaction with substrate. Ketoconazole inhibition studies suggest the presence of two non-inducible cytochrome P450 progesterone hydroxylases, one possessing 7 beta site selectivity, the other 11 alpha/15 beta site-selectivity. PMID- 8003447 TI - Transcallosal circuitry revealed by blocking and disinhibiting callosal input in the cat. AB - The purpose of this study was to obtain quantitative measures of the influence of callosal input to cells at the area 17/18 border region where transcallosal axons terminate most densely. Single-cell recordings were performed at the area 17/18 border region of the right hemisphere, while gamma-aminobutyric acid (GABA) or its antagonist, bicuculline, were applied to the transcallosal projecting regions of the left hemisphere to either block or overactivate the cells which projected to the neurons at the recording site. The results showed that visually evoked responses of the cells at the area 17/18 border were affected by administration of GABA or bicuculline to the contralateral hemisphere. Blockade of transcallosal input by application of GABA in the left hemisphere diminished the visually evoked responses of 51% of the neurons in the right hemisphere, and led to an increase in response magnitude for 17% of the neurons. Disinhibition of transcallosal input by application of bicuculline increased the evoked activity of 40% of the neurons and diminished the response magnitude of 20% of the neurons in the right hemisphere. GABA and bicuculline failed to show antagonistic effects on some cells. Thirty-two percent of the cells were affected by only one type of drug administration, and 13% of the cells showed either an increase or a decrease in responses after both GABA and then bicuculline administration. This study demonstrated complex interactions between neurons connected by the transcallosal pathway. A model of the transcallosal circuitry was proposed to explain the results. PMID- 8003448 TI - Constant light affects retinal dopamine levels and blocks deprivation myopia but not lens-induced refractive errors in chickens. AB - Chickens were raised with either translucent occluders or lenses, both under normal light cycles (12-h light/12-h dark) and in constant light (CL). Under normal light cycles, eyes with occluders became very myopic, and eyes with lenses became either relatively hyperopic (positive lenses) or myopic (negative lenses). After the treatment, retinal dopamine (DA), DOPAC, and serotonin levels were measured by high-pressure liquid chromatography (HPLC-EC). A significant drop in daytime retinal DOPAC (-20%) was observed after 1 week of deprivation, and in both DOPAC (-40%) and DA (-30%) after 2 weeks of deprivation. No changes in retinal serotonin levels were found. Retinal DA or DOPAC content remained unchanged after 2 or 4 days of lens wearing even though the lenses had already exerted their maximal effect on axial eye growth. When the chickens were raised in CL, development of deprivation myopia was reduced (8 days CL) or entirely blocked (13 days CL). Lens-induced changes in eye growth were not different after either 6 or 11 days in CL, compared to animals raised in a normal light cycle. Thirteen days of CL resulted in a dramatic reduction of DA and DOPAC levels, but serotonin levels were also lowered. The results suggest that lens-induced changes in refraction may not be dependent on dopaminergic pathways whereas deprivation myopia requires normal diurnal DA rhythms to develop. PMID- 8003449 TI - Voltage-dependent sodium channel alpha subunit immunoreactivity is expressed by distinct cell types of the cat and monkey retina. AB - Polyclonal (7493 and 7317) and monoclonal (mAb3) antibodies, generated to the alpha subunit of the voltage-gated sodium channel (alpha NaCh), were employed to assess the cell types containing alpha NaCh-like immunoreactivity in the mature cat and monkey retina. Immunoblot analyses of retinal proteins in the cat revealed that the polyclonal and monoclonal antibodies we employed labeled a band in the 260-kDa region which corresponds to the molecular mass of the alpha subunit of the NaCh. In both the cat and monkey, these antibodies immunolabeled several distinct types of retinal cells. With the polyclonal antibodies immunoreactivity was observed in ganglion cells and their intraretinal axons, in horizontal cells, and unexpectedly, in cones. In addition, in both species, a limited number of heavily labeled profiles, presumed to be bipolar cells, were seen in the inner nuclear layer. In cat and monkey the monoclonal antibody labeled axons in the fiber layer, ganglion cell somata, and a continuous band of immunoreactive cell bodies (presumed bipolar cells) situated in the outer half of the inner nuclear layer. By immunolabeling isolated cells dissociated from the cat retina, it was possible to demonstrate unequivocally that a population of bipolar cells was labeled by the monoclonal and the polyclonal antibodies we employed. The differences in the labeling observed with the monoclonal antibody as compared to the polyclonal antibodies were interpreted as reflecting the presence of different alpha-subunit subtypes in the mammalian retina. Collectively, our findings suggest that alpha NaCh-like proteins are expressed by a more diverse population of retinal cells than expected on the basis of previous physiological and immunohistochemical studies. PMID- 8003451 TI - The action spectra of cone photoreceptors in the turtle (Mauremys caspica) retina. AB - Cone photoreceptors in the turtle retina are involved in intricate neuronal interactions with other retinal neurons that modify the responses of the cones to photons absorbed in their outer segments. Therefore, the action spectra of cones strongly depend upon the conditions of measurements. This study describes an attempt to derive the action spectra of turtle cones which are the least distorted by neuronal interactions. To achieve this goal, the photoresponses of cones and horizontal cells were recorded from the turtle retina under different conditions of adaptation using different patterns of the stimulating test flashes. The sensitivity action spectra, derived from small-amplitude (<1 mV) photoresponses, were strongly affected by the recording conditions indicating the contributions of multiple neuronal inputs. Action spectra, constructed from large criterion photoresponses, were less distorted by neuronal interactions and better described the spectral properties of the "isolated" cones. The action spectra of the hyperpolarizing inputs to chromaticity-type horizontal cells were derived by stimulating these cells with mixtures of a saturating red light and a monochromatic light of different wavelength and intensity. The action spectra were constructed from the intensity of the addend component needed to "pull down" the depolarizing response to the red component by a fixed criterion. These spectra, measured in red/green and yellow/blue C-type horizontal cells, are suggested to best represent the "isolated" M-cones and S-cones, respectively. PMID- 8003450 TI - The effects of lateral geniculate nucleus, area V4, and middle temporal (MT) lesions on visually guided eye movements. AB - Visually guided saccadic eye movements to singly presented stationary targets form a bimodal distribution. After superior colliculus lesions, the so called "express saccades" that form the first mode of the distribution are no longer obtained. The aim of this study was to determine what role several other neural systems play in the generation of express and regular saccades, with the latter being those that form the second mode in the bimodal distribution. Lesions were made in the parvocellular and magnocellular portions of the lateral geniculate nucleus to disrupt either the midget system or the parasol system that originates in the retina and areas V4 and MT. The effects of the lesions were examined on the accuracy and latency of saccadic eye movements made to stationary and to moving visual targets. Following magnocellular and MT lesions deficits were observed in smooth pursuit and in the amplitude of saccades made to moving targets. However, none of the lesions produced significant changes in the bimodal distribution of saccadic latencies to stationary targets. The results suggest that express saccades and regular saccades are not selectively mediated by either the midget or the parasol systems or by areas V4 and MT. Neither are the frontal eye fields involved as had previously been shown. We suggest that the superior colliculus plays a central role in producing both express and regular saccades by virtue of highly convergent input from numerous cortical structures. PMID- 8003453 TI - Conductances evoked by light in the ON-beta ganglion cell of cat retina. AB - When a bar of light (215 x 5000 microns) illuminates the receptive field of an ON beta ganglion cell of cat retina, the cell depolarizes. Intracellular recording from the cat eyecup preparation shows that this depolarization is due to an increase in conductance (2.4 +/- 0.6 nS). Different phases of this depolarization have different reversal potentials, but all of these reversal potentials are more positive than the cell's resting potential in the dark. When the light is turned on, there is an initial transient depolarization; the reversal potential measured for this transient is positive (23 +/- 11 mV). As the light is left on, the cell partially repolarizes to a sustained depolarization; the reversal potential measured for this sustained depolarization is close to zero (-1 +/- 5 mV). When the light is turned off, the cell repolarizes further; the reversal potential measured for this repolarization is negative (-18 +/- 7 mV), but still above the resting potential in the dark (-50 mV). To explain this variety of reversal potentials, at least two different synaptic conductances are required: one to ions which have a positive reversal potential and another to ions which have a negative reversal potential. Comparing the responses to broad and narrow bars suggests that these two conductances are associated with the center and surround, respectively. Finally, since an ON-beta cell in the area centralis receives about 200 synapses, these results indicate that a single synapse produces an average conductance increase of about 15 pS during a near-maximal depolarization. PMID- 8003452 TI - Taurine and GABA in the rat retina during postnatal development. AB - The content of taurine and the immunocytochemical localization of taurine and gamma-aminobutyric acid (GABA) in the rat retina during postnatal development are described. The rat retina is immature at birth; about two-thirds of the cells are undifferentiated neuroblasts, and the taurine content per retina is approximately one-seventh of the adult value. Shortly after weaning the adult morphology and taurine content are attained. Expression of taurine immunoreactivity (taurine-IR) accompanies differentiation; in some cell types (ganglion and horizontal cells) this expression is transient, while in others (photoreceptors, bipolar, and a subpopulation of amacrine cells) it persists into the adult state. At birth, taurine-IR is localized mainly in cells in the position of ganglion cells, especially in their axons within the nerve fiber layer. This reactivity is soon lost from the somata, and disappears from the axons by 10 days of age. At 2 days of age, taurine-IR appeared additionally in somata of amacrine cells flanking the forerunner of the inner plexiform layer, and in growth cone-like processes of photoreceptors. At day 6, taurine-IR was marked in photoreceptor cell inner and outer segments, and in horizontal cells and their lateral processes. Taurine-IR was lost from horizontal cells and most amacrine cells around day 10, and appeared in bipolar cells, where it remained, with that in photoreceptors, into adulthood. Particularly striking was taurine-IR in large synaptic terminal-like processes close to the ganglion cell layer which were first seen around day 16.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8003454 TI - Contribution of linear mechanisms to the specification of local motion by simple cells in areas 17 and 18 of the cat. AB - A reverse correlation technique, which permits estimation of three-dimensional first-order properties of receptive fields (RFs), was applied to simple cells in areas 17 and 18 of cat. Two classes of simple cells were found. For one class, the spatial and temporal RF characteristics were separable, i.e. they could be synthesized as the product of spatial and temporal weighting functions. RFs in the other class were inseparable, i.e. bright and dark subregions comprising each field were obliquely oriented in space-time. Based on a linear superposition model, these observations led to testable hypotheses: (1) simple cells with separable space-time characteristics should be speed but not direction selective and (2) simple cells with inseparable space-time characteristics should be direction selective and the optimal velocity of moving stimuli should be predictable from the slope of the oriented subregions. These hypotheses were tested by comparing responses to moving bars with those predicted by application of the convolution integral. Linear predictions accounted for waveforms of responses to moving bars in detail. For cells with oriented space-time characteristics, the preferred direction was always predicted correctly and the optimal speed was predicted quite well. Most cells with separable space-time characteristics were not direction selective as predicted. The major discrepancies between measured and predicted behavior were twofold. First, 8/32 cells with separable space-time RFs were direction selective. Second, predicted directional indices were weakly correlated with actual measurements. These conclusions hold for simple cells in both areas 17 and 18. The major difference between simple RFs in these areas is the coarser spatial scale seen in area 18. These results demonstrate a significant linear contribution to the speed and direction selectivity of simple cells in areas 17 and 18. Where additional, nonlinear mechanisms are inferred, they appear to act synergistically with the linear mechanism. PMID- 8003455 TI - Organization of simple cell responses in the three-dimensional (3-D) frequency domain. AB - The amplitude spectra of simple cells in areas 17 and 18 were estimated in two and three dimensions (2-D and 3-D) using drifting sinusoidal gratings. In 2-D, responses were sampled with 16 x 16 resolution in spatial and temporal frequency at the optimal orientation. In 3-D, responses were sampled with 12 x 12 x 10 resolution in spatial frequency, orientation, and temporal frequency. For 45/50 cells studied, the spatial attributes of the receptive fields (RFs) were independent of temporal frequency except for a scale factor. The five exceptions to this general finding could be described as follows: For four area 17 cells, responses in the null direction increased with temporal frequency, reducing direction selectivity. For one area 18 cell, the optimal spatial frequency increased with temporal frequency and vice versa. The 2-D discrete Fourier transform was applied to all of the estimated amplitude spectra assuming zero spatial and temporal phase. These transforms were compared with the results of first-order reverse correlations as described in the previous paper (McLean et al., 1994). Direction selective cells exhibited excitatory subregions that were obliquely oriented in space-time in both the raw correlation data and inverse transforms of the spectral data. The slopes of the subregions found in these two measures were highly correlated. Direction indices obtained from space and frequency domain measures were comparable. We demonstrate that the spectral response profiles of most simple cells are aligned with the coordinate axes in frequency domain. That is, they may be considered one-quadrant separable, suggesting that these cells are not velocity tuned per se, but are tuned for spatiotemporal frequency. The spectral bandwidth establishes the range of velocities to which these cells will respond. These findings are consistent with the one-quadrant separability constraint of linear quadrature models. We conclude that most simple cells perform as roughly linear filters in two dimensions of space and time. PMID- 8003457 TI - The visual fields of American horseshoe crabs: two different eye shapes in Limulus polyphemus. AB - The optical alignment of individual cuticular cones in the dioptric array of the lateral eye of Limulus polyphemus was determined with a precision two-circle goniometer constructed and mounted to the stage of a compound microscope and using a new formaldehyde-induced fluorescence procedure. All measurements were made from the corneal surface of the excised eye mounted in seawater through an air/water interface perpendicular to the optic axis of the microscope. Our results revealed two variants of visual field and eye curvature which can actually be discriminated in casual examination of adult animals. We call animals possessing these two variants "morlocks" and "eloi." Adult male and female morlocks about 25 cm across the carapace have eyes which are relatively elongated, often darker in pigmentation, smaller, and relatively flatter in curvature. Morlocks have a monocular field of view of about 3.13 steradians or 50% of a hemisphere. The coverage averages 115 deg along the vertical axis and 168 deg along the horizontal axis of the eye, with maximum resolution in the anteroventral quadrant. Adult male and female eloi of comparable size have eyes which are relatively more round, often lighter in pigmentation, larger with more ommatidia, and relatively more bulged. Eloi have a monocular field of view of approximately 3.83 steradians or 61% of a hemisphere that covers 145 deg vertically and 185 deg horizontally. Eloi have more uniform resolution than morlocks with best resolution in the posteroventral quadrant. All horseshoe crabs examined, whether morlocks or eloi, have an identical orientation of the margin of the eye relative to the animals' coordinates. PMID- 8003456 TI - The role of NMDA and non-NMDA excitatory amino acid receptors in the functional organization of primate retinal ganglion cells. AB - The role of excitatory amino acid (EAA) receptors in primate retinal ganglion cell function was analyzed in a superfused retina-eyecup preparation using single unit, extracellular recording techniques. The effects of bath applied L-2-amino-4 phosphonobutyrate (APB), N-methyl-D-aspartate (NMDA), and non-NMDA EAA receptor agonists and antagonists were examined on the light-evoked responses and resting firing rates of ganglion cells. APB (30-100 microM) reduced or blocked the light evoked responses and resting firing rates of all ON-center ganglion cells; higher doses of APB (100 microM) were required to block the light-evoked responses of ON transient cells. In contrast, an increase in resting firing rates was observed when L-APB was applied to some OFF-center ganglion cells. The EAA agonists kainate (KA) (10-20 microM) and NMDA (200-350 microM) increased the firing rate of virtually all ganglion cells examined. Quisqualate (10-20 microM) increased firing in most cells, but occasionally (4/13 cases) produced inhibition. The NMDA antagonist D-amino-phosphono-heptanoic acid (D-AP7) (200-250 microM) reduced the light-evoked responses of ganglion cells by an average of 12% from control levels, while resting firing rates declined 37%. In the presence of D-AP7, the basic receptive-field characteristics of cells were not significantly altered. In contrast, two non-NMDA receptor antagonists, NBQX (2,3-Dihydroxy-6-nitro-7 sulfamoyl-benzo-(F)-quinoxalinedione) and DNQX (6,7-dinitro-quinoxaline-2,3 dione), produced substantial reductions in the light-evoked responses (82%) and resting firing rates (87%) of all ganglion cell classes. A striking observation in some neurons was the recovery of a persistent transient light-evoked response in the presence of NBQX. This NBQX-insensitive, light-evoked response was always blocked by adding D-AP7. Thus, neurotransmission from bipolar to ganglion cells in primates is mediated predominantly by non-NMDA EAA receptors, with NMDA receptors forming a minor component of the light-evoked response. PMID- 8003458 TI - Effects of calcium on rod and cone inputs to horizontal cells of the tiger salamander retina. AB - Effects of extracellular calcium on signal transmission between photoreceptors and horizontal cells (HCs) are studied in superfused isolated retina of the larval tiger salamander. Horizontal cell light response is optimal when extracellular Ca2+ is maintained between 1-2 mM. Ca2+ levels beyond this range in either direction significantly reduce the HC light response amplitude. When extracellular Ca2+ is lowered from 2 mM to 0.5 mM, the rod input to HCs is reduced whereas the cone input is not affected. In comparison, the peak voltage responses of rods are not changed whereas the cone voltage responses are enhanced in 0.5 mM Ca2+. The selective suppression of rod input to HCs is probably due to the interplay of three factors: (1) the photocurrents, (2) voltage- and time dependent membrane currents in photoreceptors, and (3) the Ca(2+)-dependent synaptic gain between photoreceptors and HCs. PMID- 8003459 TI - Expression profiling of GABAA receptor beta-subunits in the rat retina. AB - This study profiled the expression of the family of GABAA receptor beta-subunits in the adult rat retina. Using a combination of reverse transcriptase reaction followed by polymerase chain reaction (RT-PCR) with gene-specific primers, the expression of mRNAs encoding the beta 1, beta 2, and beta 3 subunits was first examined in the intact retina and then in separated retinal nuclear layers. However, it was found that a critical analysis had to be carried out at the level of the single cell in order to resolve the differential patterns of expression among the retinal cell types. When cells were isolated and identified following acute dissociation, RT-PCR revealed that individual rod photoreceptor cells expressed consistently the beta 1 and beta 2 messages while the bipolar cells expressed the beta 1 and beta 3 messages. Ganglion cells displayed considerable variability in beta-subunit expression, perhaps reflecting their functional and morphological heterogeneity in the retina. In contrast, the nonneuronal Mueller cells did not express any of the beta-subunit messages. These results indicate that the expression of GABAA receptor subunits is cell-type dependent. Furthermore, as the expression of other families of GABAA receptor subunits are profiled and the patterns of subunit assembly are better understood, our results raise the possibility that GABAA receptors with different subunit compositions can be expected to be coexpressed within a single retinal neuron. PMID- 8003460 TI - Movement of retinal along cone and rod photoreceptors. AB - Single isolated photoreceptors can be taken through a visual cycle of light adaptation by bleaching visual pigment, followed by dark adaptation when supplied with 11-cis retinal. Light adaptation after bleaching is manifested by faster response kinetics and a permanent reduction in sensitivity to light flashes, presumed to be due to the presence of bleached visual pigment. The recovery of flash sensitivity during dark adaptation is assumed to be due to regeneration of visual pigment to pre-bleach levels. In previous work, the outer segments of bleached, light-adapted cells were exposed to 11-cis retinal. In the present work, the cell bodies of bleached photoreceptors were exposed. We report a marked difference between rods and cones. Bleached cones recover sensitivity when their cell bodies are exposed to 11-cis retinal. Bleached rods do not. These results imply that retinal can move freely along the cone photoreceptor, but retinal either is not taken up by the rod cell body or retinal cannot move from the rod cell body to the rod outer segment. The free transfer of retinal along cone but not along rod photoreceptors could explain why, during dark adaptation in the retina, cones have access to a store of 11-cis retinal which is not available to rods. Additional experiments investigated the movement of retinal along bleached rod outer segments. The results indicate that retinal can move along the rod outer segment, but that this movement is slow, occurring at about the same rate as the regeneration of visual pigment. PMID- 8003461 TI - The in vivo gracilis muscle model of skeletal muscle ischemia. AB - The bilateral canine gracilis muscle has been studied as a model of acute skeletal muscle ischemia. Early investigations demonstrated that preparation of the model did not alter the energy profile of the muscle. Changes in energy metabolism during ischemia and after reperfusion have been extensively investigated using this model. Further investigations are reviewed that have explored the mechanisms of injury during reperfusion, including oxygen free radical production, calcium influx, neutrophil infiltration, and complement activation. These experiments have furthered our understanding of the pathophysiologic changes that occur in skeletal muscle after ischemia and laid the groundwork for future experiments to reduce reperfusion injury and salvage ischemic skeletal muscle. PMID- 8003462 TI - A clinically relevant small-animal model of skeletal muscle ischemia-reperfusion injury. AB - Animal models of skeletal muscle ischemia-reperfusion injury have led to a better understanding of the pathophysiology of this condition and are necessary for the evaluation of potential therapeutics. This study presents a new, well-controlled model of ischemia-reperfusion that more accurately simulates acute arterial occlusions in humans. In rabbits, a whole hindlimb is rendered reversibly ischemic by occlusion of primary and collateral arterial inflow and then reperfused for an extended period of 48 h. Ischemic injuries are standardized by defining and controlling ischemic time, limb temperature, and the extent of collateral circulation. We have characterized this model by measuring anterior tibial and soleus muscle necrosis and edema formation in groups of animals subjected to 4 h of ischemia at either 32 or 36 degrees C, with one of two extents of collateralization and with or without muscle compartment release (fasciotomy). Our results indicate the following: (1) muscle necrosis is significantly worsened by restricting the extent of collateral blood supply or by elevating ischemic temperature; (2) anterior tibial muscle is inherently more sensitive than soleus muscle to ischemic injury; (3) fasciotomy may reduce muscle necrosis by more than 50%; and (4) the amount of edema present in muscles is an unreliable indicator of actual muscle necrosis. We conclude that this new model is a practical, well-controlled, and clinically relevant preparation useful for the investigation of ischemic muscle injury. PMID- 8003464 TI - Skeletal muscle ischemia-reperfusion injury: a review of endothelial cell leukocyte interactions. AB - Ischemia-reperfusion injury remains a difficult problem facing vascular surgeons because of its associated high morbidity and mortality. The basis for tissue injury during ischemia depends on depletion of tissue oxygen and energy substrates. Cell injury, as documented cellular edema and lysosomal degranulation, begins after only 30 min of ischemia. Irreversible cellular changes occur after 4-6 h of skeletal muscle ischemia. Following acute arterial occlusion, the restoration of blood flow heralds the onset of biochemical events, forming the basis of what is known as the reperfusion syndrome. This tissue injury is maximal in areas with the greatest blood flow during reperfusion. Endothelium-leukocyte interactions play an important role in ischemia-reperfusion injury. Both endothelial and white blood cells have the biochemical machinery and capacity to generate molecular signals, to express adhesion proteins, and to produce toxic metabolic by-products. Since the microcirculatory changes in ischemia-reperfusion injury parallel those seen in inflammation, the leukocyte endothelial interaction can explain many of the reactions associated with the early phases of ischemia-reperfusion injury. PMID- 8003463 TI - Microvascular dysfunction in postischemic skeletal muscle. AB - In recent years, considerable research efforts have been directed at elucidating the mechanisms underlying the pathophysiologic alterations associated with reperfusion (reoxygenation) of ischemic (hypoxic) skeletal muscle. This intensive effort has led to the accumulation of a large body of evidence supporting the concept that reactive oxygen metabolites, generated at the onset of reperfusion, initiate the formation and release of proinflammatory agents, which subsequently attract and activate granulocytes. The activated neutrophils adhere to the microvascular endothelium, extravasate, and release cytotoxic oxidants and hydrolytic enzymes. As a consequence of these pathologic events, vascular permeability and transcapillary fluid filtration are increased and the no-reflow phenomenon (ie, some capillaries fail to reperfuse upon reinstitution of blood flow) becomes apparent. These microvascular alterations may be of considerable functional importance since the marked accumulation of fluid in the interstitial spaces, coupled with the incomplete and maldistributed blood flow, increases the functional diffusion path length for nutrients. Thus cellular nutrition is limited during reperfusion, which in turn impairs the functional recovery of postischemic muscles. Moreover, the infiltrating neutrophils are able to direct a focussed attack on myocytes, thereby exacerbating contractile dysfunction and tissue injury during reperfusion. These observations indicate that alterations in the microcirculation play a critical role in the genesis of ischemia/reperfusion injury in skeletal muscle. This review summarizes the evidence we have accumulated in support of the view that reactive oxygen metabolites and neutrophils contribute to production of postischemic microvascular dysfunction and describes the experimental models we have used to examine the mechanisms involved in the pathogenesis of ischemia and reperfusion. PMID- 8003465 TI - A persistent hindlimb ischemia model in the rabbit. AB - The study of new approaches for the treatment of limb-threatening ischemia has been hampered by the lack of a suitable animal model of persistent limb ischemia. We describe the development and evaluation of an animal model of persistent hindlimb ischemia, in which ischemia was induced in the left hindlimb of 28 rabbits by ligation of the distal external iliac artery and excision of the common and superficial femoral arteries. The severity of the ischemia and its relief in each animal were evaluated every 10 days postoperatively until day 40 (all animals) or day 90 (five animals). Nine animals developed superficial tissue necrosis in the foot, but no deaths were attributable to the ischemia-inducing procedure. Angiography demonstrated minimal collateralization and sluggish filling of distal vessels up to postoperative day 90. This was accompanied by a decrease at rest in the calf blood flow ratio (p < 0.005 vs day 0), an increase in lactic acid in the femoral venous blood (left vs right side, p < 0.002) up to postoperative day 40, and a decrease in the calf blood pressure ratio (p < 0.0001 vs day 0) up to day 90. Histologic study of the gastrocnemius muscle demonstrated evidence of atrophy and fibrosis in the left hindlimb. This model can be used to evaluate direct and indirect approaches to the treatment of chronic limb ischemia. PMID- 8003466 TI - New surgical treatment for severe limb ischemia. AB - Revascularization after prolonged complete limb ischemia may result in severe damage to skeletal muscle and systemic alterations (postischemic syndrome). Our previous experimental studies have shown that this injury can be reduced substantially by treating the jeopardized extremity by controlling the conditions of reperfusion and composition of the initial reperfusate. In the present study this concept of controlled limb reperfusion was applied in patients with prolonged severe limb ischemia. Controlled limb reperfusion was used in 14 patients after prolonged complete uni- or bilateral ischemia. The ischemic interval ranged from 5 to 21 h. Two patients were in cardiogenic shock, 11 had associated cardiac disease, and seven coexistent peripheral vascular disease. After systemic heparinization, standard thromboembolectomy was done using a Fogarty catheter. Cannulas were placed into the iliac, profunda, and superficial femoral arteries and were connected to a reperfusion set. Oxygenated blood was drawn from the iliac artery and mixed with an asanguineous solution (ratio 6:1). This controlled reperfusate was delivered into the profunda and superficial femoral arteries using a single rollerpump. The system allows control of the composition of the reperfusate (calcium, pH, osmolarity, glucose, substrate, pO2, free radical scavengers) and the conditions of reperfusion (pressure, flow, temperature). After 30 min of controlled limb reperfusion, the cannulas were removed and normal blood reperfusion started. All 12 patients who were stable hemodynamically before the operation survived the revascularization. Eleven patients, including one with acute aortic occlusion for several hours, were discharged with functional recovery of their extremities. Despite the severe ischemic insult, controlled limb reperfusion avoided amputation and profound systemic complications. Two patients who were in cardiogenic shock preoperatively died from progressive cardiac failure. We conclude that controlled arterioarterial limb reperfusion may reduce the local manifestations of the postischemic syndrome after prolonged periods of ischemia, may salvage limbs thought previously to be damaged irreversibly by prolonged ischemia, and can be done easily in the operating room. PMID- 8003467 TI - Determination by Raman spectroscopy of the pKa of N5 of dihydrofolate bound to dihydrofolate reductase: mechanistic implications. AB - Dihydrofolate reductase (DHFR) catalyzes the reduction of dihydrofolate (H2folate) to tetrahydrofolate by NADPH, and this requires that the pteridine ring be protonated at N5. A long-standing puzzle has been how, at physiological pH, the enzyme can protonate N5 in view of its solution pKa of 2.6 and the fact that the only proton-donating group in the pterdine binding site, Asp-27, hydrogen bonds not to N5 but to the 2-amino group and N3 of the pterin ring. We have determined the pKa of N5 of dihydrofolate in the Escherichia coli DHFR/NADP+/H2folate ternary complex by Raman difference spectroscopy and found that the value is 6.5. In contrast, the pKa of N5 is less than 4.0 in either the binary complex, the ternary complex with an analogue of NADPH (H2NADPH), or the Asp27 to serine mutant DHFR (D27S) ternary complex with NADP+. Thus, one need not invoke proton donation from Asp-27 to N5 via a series of bound water molecules and/or pteridine-ring substituents. We propose instead that the N5 protonated form of H2folate is stabilized directly at the active site in the DHFR/NADPH/H2folate complex by specific interactions that form only in the ternary complex, involving perhaps a bound water molecule, the carboxamide moiety of the coenzyme, and/or the local electrostatic field of the enzyme molecule, to which an important contribution may be made by Asp-27. PMID- 8003468 TI - Serine 90 is required for enzymic activity by tRNA-guanine transglycosylase from Escherichia coli. AB - An Escherichia coli mutant described by Noguchi et al. [Noguchi, S., et al. (1982) J. Biol. Chem. 275, 6544-6550] contains tRNA lacking the hypermodified wobble nucleoside queuosine (Q) due to an inactive tRNA-guanine transglycosylase (TGT). TGT catalyzes the posttranscriptional base exchange of the Q precursor preQ1 with the genetically encoded guanine in tRNA(Asp,Asn,His,Tyr). The mutant tgt gene was cloned and sequenced; it contained a single point mutation resulting in the change of serine 90 to phenylalanine. Overexpression of the mutant gene yielded TGT(S90F) that showed a reduced solubility and did not purify in the same fashion as the wild-type enzyme. TGT(S90F) has no detectable enzymic activity. To determine whether serine 90 performs a catalytic role in the TGT reaction or whether the loss of activity was caused solely by a conformational change of the enzyme, we used site-specific mutagenesis to construct serine-to-alanine (S90A) and serine-to-cysteine (S90C) mutants. Both S90A and S90C mutants were purified in a manner identical to that used for the wild-type enzyme. SDS-PAGE of dimethyl suberimidate-cross-linked mutants showed a pattern identical to that of the wild type TGT, indicative of a trimeric quaternary structure. Native PAGE of wild-type and mutant TGTs in the absence and presence of substrate tRNA exhibited band shifts indicating that both mutants retain the ability to bind tRNA.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8003469 TI - The active site architecture of a short-chain dehydrogenase defined by site directed mutagenesis and structure modeling. AB - A high-resolution crystal structure is not currently available for Drosophila alcohol dehydrogenase. A detailed three-dimensional model for this enzyme, based on the structure of 3 alpha,20 beta-hydroxysteroid dehydrogenase, has been generated by extensive computer modeling studies. Aspects of the model concerned with coenzyme binding have been tested by site-directed mutagenesis of residues Gly-14 to Ala, Gly-19 to Ala, Asp-38 to Ala, and Pro-214 to Ser. All enzymes have been characterized in terms of kinetic constants, relative stabilities to guanidinium chloride, and heat inactivation. The contribution of NAD binding to the stabilization of each of the enzymes was also measured. The results obtained with enzymes mutated at positions 14, 38, and 214 are in accordance with published data on Drosophila alcohol dehydrogenase and suggest interactions of these residues with the cofactor NAD. The introduction of a methyl group at residue Gly-19 abolished the ability of the enzyme to utilize NADP instead of NAD. This reflects a proximity of residue Gly-19 to the ribose ring of the bound cofactor. This result, coupled to the three-dimensional model built for Drosophila alcohol dehydrogenase, suggests a binding mechanism for the cofactor NAD different from that found for 3 alpha,20 beta-dehydroxysteroid dehydrogenase and similar to that found in the crystal structure of rat liver dihydropteridine reductase. The model of Drosophila alcohol dehydrogenase also enables many previous observations from chemical modification, sequence comparisons, site directed mutagenesis, and limited proteolysis experiments to be placed into a structural context. An active site architecture is proposed involving a loop closure mechanism similar to that of lactate dehydrogenase.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8003470 TI - Interactions of mycobacterial glycopeptidolipids with membranes: influence of carbohydrate on induced alterations. AB - Glycopeptidolipids (GPLs) are specific constituents of mycobacteria known as opportunistic pathogens. The influence of the carbohydrate moiety on GPL-induced membrane alterations was examined with GPLs bearing 1-5 sugar residues (GPL-1 to GPL-5) and a sulfated GPL (S-GPL-2). GPLs decreased the ADP/O ratio and increased controlled respiration of isolated mitochondria. The more polar GPLs were the less active, with the following order of efficiency: GPL-1 > GPL-2 > S-GPL-2 = GPL-3 = GPL-5. GPL-1 and GPL-2 increased passive permeability of liposomes to carboxyfluorescein (GPL-1 > GPL-2), while GPL-3 and GPL-5 were inactive. GPL-2 and GPL-3 decreased the transmembrane electrical potential (delta psi) in isolated mitochondria (GPL-2 > GPL-3). These results suggest that GPLs uncouple oxidative phosphorylation by increasing the passive permeability of the mitochondrial membrane to protons. Compression isotherms of GPL-2 monolayers showed that, at low surface pressure, the area per GPL-2 molecule was about 5 times that of an acyl chain: it is likely that the peptide moiety was at the air/water interface. With an increase in the surface pressure, its area decreased, down to that of a tightly packed acyl chain. It is postulated that the glycopeptidic moiety can be either at in the interface or dipping into the water.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8003471 TI - Site-directed mutagenesis and NMR studies of histidine-385 mutants of 5 enolpyruvylshikimate-3-phosphate synthase. AB - The site-directed mutagenesis of His-385 of 5-enolpyruvylshikimate-3-phosphate (EPSP) synthase is reported. The steady-state kinetics for two mutants, H385Q and H385A, are compared with that of the wild-type enzyme. H385Q EPSP synthase was found to have 25% wild-type enzyme activity, whereas H385A EPSP synthase retained 1% activity. The KM values for Pi and shikimate 3-phosphate were unaffected, whereas the KM for phosphoenolpyruvate (PEP) was increased 10 times for H385Q EPSP synthase. The KM for EPSP was unaffected in H385Q but raised by a factor of 10 in H385A EPSP synthase. The binding of glyphosate was studied by fluorescence spectroscopy and by 31P NMR spectroscopy. Direct observation of the enzyme intermediate complexes by 13C NMR spectroscopy with [2,3-13C]phosphoenolpyruvate was studied for the mutant enzymes and compared with the wild type. Under equilibrium conditions, H385A EPSP synthase does not accumulate enzyme-bound EPSP. These results suggest that, while critically located in the PEP binding site, His-385 is not the residue responsible for initiating catalysis through the protonation of PEP. PMID- 8003472 TI - Biosynthesis of (7-mercaptoheptanoyl)threonine phosphate. AB - The biosynthesis of (7-mercaptoheptanoyl)threonine phosphate (HS-HTP) has been studied in the methanogenic bacteria Methanococcus volta and Methanosarcina thermophila. Growth of these cells in medium containing [7,7-2H2]-7 mercaptoheptanoic acid, [3,4,4,4-threonine-2H4]-N-(7-mercaptoheptanoyl)threonine, [7,7-2H2]-N-(7-mercaptoheptanoyl)threonine, or DL-[3,4,4,4-2H4]threonine led to the generation of labeled HS-HTP containing a portion of the molecules with the same number of deuteriums as the precursor molecule. This result indicated that each of these labeled molecules can serve as a precursor for the biosynthesis of HS-HTP. Cell-free extracts of these methanogens were shown to carry out the ATP dependent phosphorylation of N-(7-mercaptoheptanoyl)threonine to HS-HTP. These observations indicate that the biosynthesis of HS-HTP involves the coupling of mercaptoheptanoic acid with threonine to form (7-mercaptoheptanoyl)threonine, which is then phosphorylated to HS-HTP. PMID- 8003473 TI - Product binding modulates the thermodynamic properties of a Megasphaera elsdenii short-chain acyl-CoA dehydrogenase active-site mutant. AB - Previous work has shown that the redox properties of Megasphaera elsdenii short chain acyl-CoA dehydrogenase (SCAD) are specifically modulated upon the binding of the substrate/product couple, allowing the reaction to proceed thermodynamically [Stankovich, M.T., & Soltysik, S. (1987) Biochemistry 26, 2627 2632]. The focus of this study on the Glu367Gln SCAD mutant protein is to gain an understanding of this phenomenon. The active-site mutant Glu367Gln SCAD inactivates the reductive and oxidative pathways and allows the effects of substrate (butyryl-CoA) and product (crotonyl-CoA) binding on the redox properties of the Glu367Gln SCAD mutant protein to be determined separately. Red anionic semiquinone was found to be thermodynamically stabilized in coulometric/potentiometric reductions of both butyryl-CoA- and crotonyl-CoA complexed Glu367Gln SCAD. Reduction potential measurements showed that butyryl CoA binding has little effect on the reduction potential of Glu367Gln SCAD. Crotonyl-CoA complexation, however, shifted the reduction potential of the Glu367Gln SCAD mutant protein by 30 mV in the positive direction. This modulation is similar to the 60-mV positive shift observed in native M. elsdenii SCAD upon complexation with the substrate/product couple [Stankovich, M.T., & Soltysik, S. (1987) Biochemistry 26, 2627-2632]. Thus, product binding and not substrate binding, thermodynamically regulates M. elsdenii SCAD. We propose that this observation is best explained by assuming that the product resembles an intermediate in the catalytic mechanism that is responsible for facilitating isopotential electron transfer from the substrate to the enzyme. PMID- 8003474 TI - Structure-activity relationships in the oxidation of benzylamine analogues by bovine liver mitochondrial monoamine oxidase B. AB - The influence of para and meta substitution of benzylamine on its interaction with bovine liver mitochondrial monoamine oxidase B (MAO B) has been investigated by steady-state and reductive half-reaction anaerobic stopped-flow kinetic approaches. Steady-state kinetic properties of each benzylamine analogue suggest that para or meta substitution does not alter the mechanistic pathway of catalysis [Husain, M., et al. (1982) Biochemistry 21, 595-600]. All analogues tested exhibited Dkcat values ranging from 5.5 to 8.9 and D[kcat/Km(amine)] values ranging from 3.3 to 8.1 D[kcat/Km(O2)] values of approximately 1 are observed for all substrate analogues. Values for Kd were calculated from steady state isotope effect data [Klinman, J.P., & Matthews, R.G. (1985) J. Am. Chem. Soc. 107, 1058-1060] and are in good agreement with Ks values determined from analysis of the rate of MAO B reduction as a function of benzylamine analogue concentration in reductive half-reaction experiments. A linear correlation of benzylamine analogue Kd values with the hydrophobicity parameter (phi) is observed for the para-substituted analogues where the binding affinity increases with increasing hydrophobicity of the substituent. Statistical treatment of the correlation shows a small negative contribution to binding by the van der Waals volume (VW) of the para substituent. meta-Substituted benzylamine analogues show a decreased binding affinity with the VW of the substituent and no correlation with the hydrophobicity value of the substituents tested. No spectral evidence was found for any flavin radical intermediates during the time course of MAO B flavin reduction in anaerobic reductive half-reduction stopped-flow experiments with any of the alpha,alpha-diprotio- or alpha,alpha-dideuteriobenzylamine analogues tested. The limiting rates of enzyme reduction exhibit large Dk values (6.5-14.1) for all of the analogues tested. para-Substituted benzylamine analogues reduce MAO B with limiting rates that correlate with the steric influence (Es value) of the substituent. Statistical analysis shows the rate of MAO B reduction by para-substituted analogues to be retarded by increased values of Es and, with a smaller contribution, by the hydrophobicity value of the substituent. The rate of MAO B reduction by meta-substituted benzylamine analogues is essentially independent of the nature of the substituent. No evidence was found for any electronic contribution to the rate of MAO B flavin reduction by any of the analogues tested. These data demonstrate the steric orientation of the substrate to be important in the rate of amine oxidation by MAO B and that ring meta substituents favor this orientation.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8003476 TI - Substrate specificity is determined by amino acid binding pocket size in Escherichia coli phenylalanyl-tRNA synthetase. AB - Alanine at position 294 (Ala294) within the motif 3 consensus of Escherichia coli phenylalanyl-tRNA synthetase alpha subunit has previously been implicated as a determinant of amino acid specificity. To characterize the role of Ala294, the catalytic effects of amino acid replacements at this position were tested with purified wild-type and mutant phenylalanyl-tRNA synthetases. We show that Ala294 is involved in amino acid binding and that it influences specificity as a determinant of binding pocket size. Replacement of Ala294 by either glycine or serine, thereby increasing or decreasing the size of the binding pocket, respectively, reduces affinity for phenylalanine. The Gly294 mutant shows a relaxed specificity toward synthetic para-halogenated phenylalanine analogues, the apparent dissociation constant Km increasing in direct relation to an increase of the van der Waals radius of the para group, thus confirming the role of position 294 in determining amino acid binding pocket size. For the substrate analogue p-chlorophenylalanine, attachment to tRNA and in vivo incorporation into cellular protein by the Gly294 mutant were demonstrated. Tyrosine activation was also improved with this mutant, but the resulting enzyme-Tyr-adenylate complex was rapidly hydrolyzed, indicating the presence of a proofreading mechanism in E. coli phenylalanyl-tRNA synthetase. PMID- 8003475 TI - Dual function for poly(ADP-ribose) synthesis in response to DNA strand breakage. AB - Soluble extracts of human cells repair gamma-ray-induced single-strand breaks in DNA. Accompanying NAD-dependent automodification of poly(ADP-ribose) polymerase is required for effective DNA rejoining. The kinetics of poly(ADP-ribose) synthesis by this polymerase, and subsequent polymer degradation by poly(ADP ribose) glycohydrolase, have been compared with the rate of DNA repair. The results agree with previous in vivo data. In response to addition of gamma irradiated plasmid DNA, rapid and heavy automodification of poly(ADP-ribose) polymerase occurred in NAD-containing human cell extracts. After 2 min at 30 degrees C, when very little DNA rejoining had yet occurred, synthesis of long polymers essentially ceased, although only a minor fraction of the NAD had been consumed. Poly(ADP-ribose) chains were then reduced to oligomer size by poly(ADP ribose) glycohydrolase. These short chains were present for longer times and were sufficient to permit DNA repair. Thus, most but not all poly(ADP-ribose) synthesis could be suppressed without marked inhibition of DNA repair, and prolonged occurrence of long poly(ADP-ribose) chains in consequence to glycohydrolase inhibition did not improve DNA repair. The temporary presence of short poly(ADP-ribose) chains on poly(ADP-ribose) polymerase avoids inhibition of excision-repair by that protein, but the initial very transient formation of long and branched chains of poly(ADP-ribose) in response to DNA damage apparently serves an entirely different purpose. Local poly(ADP-ribose) synthesis in the vicinity of a DNA strand interruption causes negative charge repulsion, and this may function to prevent accidental homologous recombination events within tandem repeat DNA sequences. PMID- 8003477 TI - Investigation of ionizable residues critical for sequence-specific enzymatic DNA modification: protein modification and steady-state and pre-steady-state kinetic pH analyses of EcoRI DNA methyltransferase. AB - Steady-and pre-steady-state pH kinetic analyses are widely used methods to investigate important ionizable groups in enzyme-catalyzed reactions. The first such analysis to identify ionizable residues critical for sequence-specific modification of DNA is presented. EcoRI DNA methyltransferase uses S-adenosyl-L methionine (AdoMet) to catalyze the N6 methylation of the second adenine in the double-stranded DNA sequence GAATTC. The kinetic mechanism was previously shown to be steady-state-ordered bi bi in which AdoMet binds first followed by DNA addition [Reich, N. O., & Mashhoon, N. (1991) Biochemistry 30, 2933-2939]. Steady state parameters are strongly dependent on pH and implicate at least four residues with pKa values between 8.2 and 8.9 in the free enzyme and AdoMet-Bound enzyme and one residue with an apparent pKa of 6.0. The data obtained are consistent with the enzyme binding the form of AdoMet in which the alpha amino group is protonated. Two protein residues with an apparent pKa between 8.9 and 9.2 were implicated within the central complex (enzyme-DNA-AdoMet). The general insensitivity of all steady-state parameters to pH changes between pH 6.0 and 8.0 suggests that no critical protein residues undergo ionization-state changes in this range. The lack of significant pH-dependent changes in protein fluorescence and DNA thermal stability suggests minimal structural changes in either macromolecule. In support of the steady-state results single-turnover experiments reveal minimal pH dependence of the methylation rate constant between pH 5.53 and 8.6. Thus, no amino acids critical for catalysis undergo ionization-state changes in this range.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8003478 TI - Sequence-specific DNA displaces 6-p-toluidino-2-naphthalenesulfonate bound to a hydrophobic site on the DNA-binding domain of Drosophila c-myb. AB - The N-terminal DNA-binding domain of c-myb oncoprotein binds to DNA in a sequence specific manner. The domain, consisting of three imperfect tandem repeats, has tryptophan residues at very regular intervals and this is believed to be of some significance in the DNA-binding activity of the protein. We have found that the hydrophobic-site-specific probe 6-p-toluidino-2-naphthalenesulfonate (TNS) binds to the bacterially expressed DNA-binding domain of Drosophila c-myb protein (R123). TNS has a single binding site on this protein with an apparent dissociation constant in the range of (5-8) x 10(-7) M. When the TNS-protein complex was treated with an oligomeric DNA duplex having a cognate myb-binding site, the TNS was displaced from the complex. Nonspecific DNA duplex oligomers were ineffective, indicating that TNS displacement was a sequence-specific process. We examined further some features of the TNS-binding site on the protein, taking advantage of the fluorescence properties of the protein and the bound TNS. Our data indicate that the TNS binding occurs in a peripheral site on the protein in a manner that allows the bound TNS to be solvent accessible. Furthermore, there are indications that tyrosine(s) and tryptophans of the protein mediate resonance energy transfer to the bound TNS. From fluorescence quenching data of the protein and protein-TNS complex, we could assess that both solvent-accessible and internal tryptophans are in the vicinity of the bound TNS. (ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8003479 TI - Replication of DNA templates containing the alpha-anomer of deoxyadenosine, a major adenine lesion produced by hydroxyl radicals. AB - The alpha-anomer of deoxyadenosine (alpha-dA) is a major adenine lesion produced by hydroxyl radicals in DNA. To assess its biochemical effects on DNA replication, alpha-dA was site-specifically incorporated into oligodeoxyribonucleotide templates using phosphoramidite chemistry. alpha-dA in the template constituted a transient block to DNA synthesis catalyzed by Escherichia coli DNA polymerase I Klenow fragment (polI), but translesional synthesis occurred after prolonged incubation. Primer extension assays and Maxam Gilbert sequencing of newly synthesized products revealed that alpha-dA directed not only incorporation of the correct nucleotide, dTMP, opposite the lesion but also misincorporation of dAMP and dCMP. dGMP was barely incorporated under these conditions. The order of the incorporation frequency at the alpha-dA site was affected by the nearest neighbor base pair 3' to the lesion. T7 and Taq DNA polymerases, as well as RAV-2 reverse transcriptase, showed a selectivity similar to that of PolI with respect to the nucleotide incorporation opposite alpha-dA, suggesting that the discrimination of nucleotides associated with alpha-dA is independent of the origin of DNA polymerases and is an intrinsic feature of the lesion. The mutational spectrum predicted for alpha-dA (i.e., A-->G transitions and A-->T transversions) is significantly different from those reported for other hydroxyl radical induced DNA lesions such as abasic sites or 7,8-dihydro-8 oxoguanine, both primarily directing misincorporation of A. Possible biological consequences and the mechanism of dNTP discrimination associated with alpha-dA are discussed. PMID- 8003480 TI - Positive and negative hepatic regulation of the human type II phospholipase A2 gene. AB - To identify the elements which regulate the liver transcription of the human type II phospholipase A2 gene and its stimulation by interleukin 6, the 5' flanking region from -1614 to +806 and several 3' and 5' deleted fragments have been analyzed in CAT assays. Negative regulatory elements have been located in the regions -1614 to -326 and +20 to +806. The fragment -326 to +20 contains the main elements required for the transcription as well as for the stimulation by interleukin 6. Footprinting assays have been performed on this region and showed four protected elements, A [-35;-6], B [-125;-86], C [-209;-176], and D [-247; 211]. Deletion of element D enhanced the transcription of the reporter gene 10.5 fold compared to the [-326;+20]-CAT construct. Further deletions up to position 87 which removed both the elements B and C or the substitution of element C by a nonspecific sequence lowered the promoter activity to 23% and 70% of the control, respectively. These results indicate that element C binds positive regulatory factors and element D binds a negative regulatory factor. Furthermore, stimulation by interleukin 6 is lost when element C is substituted or deleted. As shown by the footprinting and band shift assays, the transcription factors C/EBP alpha and C/EBP beta can bind to elements C and D but the dissociation constant (Kd) of C/EBP alpha is 10 times lower for element C (0.6 nM) than for element D (5.8 nM). Band shift experiments using rat liver nuclear extracts showed that element C formed four heat stable complexes, some of which could be supershifted by anti C/EBP alpha antibodies. The binding of C/EBP factors to element C was confirmed by competition with previously described oligonucleotide and nucleotide substitution of element C. Band shift experiments using rat liver nuclear extracts showed that element D formed one major DNA-protein complex. This complex could be competed out by oligonucleotides containing a cAMP responsive element (CRE) but not by oligonucleotides containing the binding site of C/EBP. However, anti-CREB antibodies did not supershift this complex. Methylation interference experiments showed the involvement of a G nucleotide upstream to the sequence homologous to CRE in the binding of the hepatic nuclear factors.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8003481 TI - Interaction of spin-labeled apocytochrome c and spin-labeled cytochrome c with negatively charged lipids studied by electron spin resonance. AB - Apocytochrome c has been spin-labeled with a nitroxide derivative of maleimide on a cysteine residue at either position 14 or position 17 in the N-terminus. Yeast cytochrome c was spin-labeled with the same maleimide derivative on its single free cysteine residue at position 102 in the C-terminus. The ESR spectra of spin labeled apocytochrome c have been characterized in different environments with respect both to the conformation of the protein and to its association with lipid. In buffer, the spectrum of spin-labeled apocytochrome c indicates high mobility, characteristic of the unfolded structure of the apoprotein, and that of spin-labeled cytochrome c is only slightly less mobile, suggesting that the site labeled is situated at the surface of the folded holoprotein. Upon binding the spin-labeled protein to negatively charged lipid membranes composed of dioleoylphosphatidylglycerol (DOPG), the ESR spectra of apocytochrome c evidence a large reduction in the mobility of the spin-label group, as also do those of yeast cytochrome c. In the case of apocytochrome c, this immobilization most likely arises from both an increase in secondary structure and a partial penetration of the protein into the lipid bilayer, in addition to the electrostatic interaction with the lipid headgroups, whereas for cytochrome c the immobilization observed arises primarily from an intimate association with the membrane surface. When the spin-labeled holocytochrome c is denatured by heating and is bound to DOPG bilayer membranes, a rather mobile ESR spectrum is observed, which demonstrates that the spin-label is located at the surface of the membrane in this case. The ESR spectra of spin-labeled apocytochrome c bound to mixed bilayers of dimyristoylphosphatidylglycerol and dimyristoylphosphatidylcholine (DMPC) consist of both an immobile and a mobile component. The proportion of the mobile component is increased by increasing the mole fraction of the zwitterionic DMPC in the mixed bilayers. The mobile component represents a localization of apocytochrome c at the membrane surface, whereas the immobile component most probably represents the penetration of the precursor protein into the membrane interior. The immobile component assigned to membrane penetration of the precursor protein is still present at negatively charged lipid contents comparable to those in the native mitochondrial system. The results are discussed in relation to the conformation of apocytochrome c, its interaction with lipid, and the import of the apoprotein into mitochondria. PMID- 8003482 TI - Mechanism of aldose reductase inhibition: binding of NADP+/NADPH and alrestatin like inhibitors. AB - Aldose reductase enfolds NADP+/NADPH via a complex loop mechanism, with cofactor exchange being the rate-limiting step for the overall reaction. This study measures the binding constants of these cofactors in the wild-type enzyme, as well as a variety of active-site mutants (C298A, Y48H, Y48F, Y209F, H110A, W219A, and W20A), and seeks to identify the binding site and mechanism of the aldose reductase inhibitor alrestatin in the recombinant human enzyme. All the mutant enzymes, regardless of their enzyme activities, have normal or only slightly elevated coenzyme binding constants, suggesting a tertiary structure similar to that of the wild-type enzyme. Binding of alrestatin was detected by fluorescence assays, and by an ultrafiltration assay which measures the fraction of unbound alrestatin. Alrestatin binds preferentially to the enzyme/NADP+ complex, consistent with the steady-state inhibition pattern. Alrestatin binding and enzyme inhibition were abolished in the Tyr48 mutants Y48F and Y48H, implicating the positively charged anion well formed by the Asp43-/Lys77+/Tyr48(0)/NADP+ complex in inhibitor binding (Harrison et al., 1994; Bohren et al., 1994). The enzyme mutant W20A severely affected the inhibitory potencies of a variety of commercially developed aldose reductase inhibitors (zopolrestat, tolrestat, FK366, AL1576, alrestatin, ponalrestat, and sorbinil). Inhibition by citrate, previously shown to bind to the positively charged anion well, was not affected by this mutation. Inhibitors with flexible double aromatic ring systems (Zopolrestat, FK366, and ponalrestat) were less affected than others possessing a single aromatic ring system, suggesting that the additional pharmacophor ring system stabilizes the inhibitor by interaction at some other hydrophobic site.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8003483 TI - Whole-cell detection by 13C NMR of metabolic flux through the C1-tetrahydrofolate synthase/serine hydroxymethyltransferase enzyme system and effect of antifolate exposure in Saccharomyces cerevisiae. AB - Folate-mediated one-carbon metabolism is critical for the synthesis of numerous cellular constituents required for cell growth. A potential source of one-carbon units is formate. This one-carbon unit is activated to 10-formyltetrahydrofolate via the synthetase activity of the trifunctional enzyme C1-tetrahydrofolate (THF) synthase for use in purine synthesis or can be further reduced to 5,10-methylene THF by the dehydrogenase activity of the same enzyme. 5,10-Methylene-THF is used by serine hydroxymethyltransferase (SHMT) in the synthesis of serine. Recently, 13C NMR has been used to establish that the C1-THF synthase/SHMT enzyme system is the only route from formate to serine in vivo in the yeast Saccharomyces cerevisiae [Pasternack et al. (1992) Biochemistry 31, 8713-8719]. In vitro studies have considered the kinetics of the C1-THF synthase/SHMT enzyme system in the catalytic conversion of formate to serine [Strong et al. (1987) J. Biol. Chem. 262, 12519-12525]. In the present work, we begin to study the kinetics of this two-enzyme system in its natural environment. Provision of [13C]formate and direct detection of an intracellular accumulating pool of [3-13C]serine by 13C NMR of whole cells allow us to monitor the rate of flux through this enzyme system in vivo. The rate of accumulation of soluble [3-13C]serine under [13C]formate-saturating conditions is 13.0 +/- 1.2 microM/min relative to an external standard of serine in D2O. The extracellular formate concentration at half-maximal flux was determined to be 900 microM.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8003484 TI - Mannose transporter of Escherichia coli. Backbone assignments and secondary structure of the IIA domain of the IIABMan subunit. AB - The mannose transporter of Escherichia coli consists of two transmembrane and one peripheral protein subunit. The complex acts by a mechanism which couples translocation of the substrate with substrate phosphorylation. The peripheral IIABMan is a homodimer. The IIABMan monomer itself contains two domains which are linked by an Ala-Pro-rich hinge and which are both transiently phosphorylated at histidyl residues. The IIA and IIB domains can be separated by limited proteolysis. The IIA domain has a dimer molecular mass of 2 x 14 kDa. Almost complete 1H, 13C, and 15N NMR assignments of the backbone resonances of IIAMan have been achieved using 3D and 4D double-and triple-resonance techniques. Secondary structure elements were derived from NOE data. The IIA domain consists of a central beta-sheet of four parallel and one antiparallel strand (strand order 5 4 3 1 2) with helices on both sides of the sheet. The active-site His-10 is located in a loop at the C-terminus of beta-strand 1. This loop and the loop after strand 3 are at the topological switch point of the sheet. PMID- 8003485 TI - 2H NMR studies of isomeric omega 3 and omega 6 polyunsaturated phospholipid membranes. AB - The properties of aqueous multilamellar dispersions of [2H31]16:0-alpha 18:3 PC (1-[2H31]palmitoyl-2-cis,cis,cis-octa-9,12,15- trienoylphosphatidylcholine) and of [2H31]16:0-gamma 18:3 PC (1-[2H31]palmitoyl-2-cis,cis,cis-octa-6,9,12 trienoylphosphatid ylcholine) were compared by broadline 2H NMR spectroscopy. These isomeric phospholipids differ only in the location of the unsaturations in the sn-2 chain. The alpha 18:3 chain has double bonds at delta 9, 12, and 15 positions whereas in the gamma 18:3 chain they are at positions delta 6, 9, and 12. Moment analysis of spectra recorded as a function of temperature reveals dramatically distinct phase behavior for the two isomers. The gel to liquid crystalline transition for [2H31]16:0-alpha 18:3 PC membranes exhibits broad hysteresis which is characterized by a mid point temperature of -9 degrees C and 20 degrees C on heating and cooling, respectively. In contrast, the phase transition of [2H31]16:0-gamma 18:3 PC membranes does not exhibit hysteresis and occurs over a lower temperature range centred on -27 degrees C. Appreciably different molecular ordering also exists within the membranes in the liquid crystalline state. Average order parameters SCD are smaller in [2H31] 16:0-alpha 18:3 PC than in [2H31]16:0-gamma 18:3 PC by 10% at the same temperature and by 20% at equal reduced temperature. Smoothed order parameter profiles generated from depaked spectra clarify the nature of the difference.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8003486 TI - Synthetic S-2 and H-5 segments of the Shaker K+ channel: secondary structure, membrane interaction, and assembly within phospholipid membranes. AB - Current models of voltage-activated K+ channels predict that the channels are formed by the coassembly of four polypeptide monomers, each of which consists of six transmembrane segments (S1-S6) and long terminal domains. The aqueous pores are thought to be composed of the conserved H-5 regions contributed by four monomers. In this study, two putative membrane-embedded segments of the Shaker K+ channel were synthesized. One segment corresponds to the putative, transmembrane helix S-2 (amino acids 275-300), and the other corresponds to the highly conserved 12 amino acid residues within the H-5 region [amino acids 432-443, designated (12)H-5]. Structural and functional characterization at elevated lipid/peptide molar ratios (> 3000:1) was performed on the two segments, as well as on a previously synthesized 21 amino acid long peptide with a sequence resembling the entire H-5 region (designated (21)H-5) (Peled & Shai, 1993). Circular dichroism spectroscopy revealed that S-2 adopts predominantly alpha helical structure in both trifluoroethanol and 35 mM SDS (78% or 99%, respectively), while (12)H-5 and (21)H-5 adopt low alpha-helical structure only in the presence of 35 mM SDS. Functional characterization demonstrated that S-2 and (12)H-5 segments bind to zwitterionic phospholipids, with partition coefficients on the order of 10(4) M-1. Resonance energy transfer measurements, between donor/acceptor-labeled pairs of peptides, revealed that the peptides self associate in their membrane-bound state, which may correlate with the existence of functional interactions between the conserved (12)H-5 regions of different subunits of K+ channels (Kirsch et al., 1993).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8003487 TI - Structural determinants in the interaction of Shaker inactivating peptide and a Ca(2+)-activated K+ channel. AB - Shaker B inactivating peptide (BP) binds to its receptor in maxi KCa channels obstructing the flow of ions through them. The interaction between KCa channels and BP mutants, with different net charge and hydrophobicity, revealed several structural features of the KCa channel internal mouth. Increasing BP net positive charge or decreasing the internal milieu ionic strength increased the affinity and rate of association, while increasing hydrophobicity augmented blocking times and had limited or no effect on on-rates. These results uncover (a) the presence of negative charges in or near the BP receptor and (b) the existence of a hydrophobic contact surface in the internal channel vestibule that is a structural constituent of the BP receptor in maxi KCa channels. PMID- 8003488 TI - Induction of a new metallothionein isoform (MT-IV) occurs during differentiation of stratified squamous epithelia. AB - A new member of the metallothionein (MT) gene family was discovered that lies about 20 kb 5' of the MT-III gene in both mouse and human. The MT-IV proteins are highly conserved in both species and have a glutamate insertion at position 5 relative to the classical MT-I and MT-II proteins. Murine MT-IV mRNA appears to be expressed exclusively in stratified squamous epithelia associated with oral epithelia, esophagus, upper stomach, tail, footpads, and neonatal skin. The MT derived from tongue epithelium contains both zinc and copper. Many of these epithelia develop parakeratosis during zinc deficiency in the rat. In situ hybridization reveals intense labeling of MT-IV mRNA in the differentiating spinous layer of cornified epithelia, whereas MT-I is expressed predominantly in the basal, proliferative layer; thus, there is a switch in MT isoform synthesis during differentiation of these epithelia. We suggest that MT-IV plays a special role in regulating zinc metabolism during the differentiation of stratified epithelia. PMID- 8003489 TI - Pregnancy-specific glycoprotein gene expression and the induction by 5-bromo-2' deoxyuridine. AB - The pregnancy-specific glycoproteins (PSGs) of the placenta, members of the immunoglobulin superfamily, are encoded by multiple linked genes located on chromosome 19. To study the control of PSG expression, we have immortalized differentiated human placental cells (HP-A1) temperature-sensitive for transformation by a recombinant adenovirus-(ori-)-SV40 tsA mutant virus. We now show that expression of the PSG gene in HP-A1 cells is temperature-sensitive. At the permissive temperature (33 degrees C), these cells expressed low levels of PSG mRNA and synthesized a 64-kDa PSG. Shifting HP-A1 cells to a nonpermissive temperature (39.5 degrees C) increased PSG mRNA expression and biosynthesis with preferential increase in the synthesis of a 54-kDa and a low level of a 72-kDa PSG. Moreover, PSG expression was greatly induced by 5-bromo-2'-deoxyuridine (BudR), which selectively increased synthesis of PSGs of 72 and 54 kDa. In the presence of BudR, HP-A1 synthesized PSGs of 72, 64, and 54 kDa, similar to the pattern seen with placental PSGs. Ribonuclease protection assays demonstrated that HP-A1 cells express the majority of PSG mRNAs and BudR stimulated expression of PSG1 and PSG1-like transcripts. Reverse transcription and polymerase chain reaction analysis using PSG gene-specific primers demonstrated that untreated HP A1 cells expressed primarily PSG1, PSG2, PSG4, and PSG5 mRNAs. BudR stimulated the expression of all PSG transcripts except PSG4. Moreover, in transient expression assays, BudR increased chloramphenicol acetyltransferase (CAT) expression directed by PSG1-I, PSG4, PSG5, PSG6, and PSG11 promoter-CAT fusion genes.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8003490 TI - Genetic identification of an autoinhibitor in CDPK, a protein kinase with a calmodulin-like domain. AB - CDPKs are a family of calcium (Ca2+)-dependent protein kinases which are defined by a carboxyl-terminal calmodulin-like domain. Mutational analysis indicates that the junction domain, which joins the kinase and calmodulin-like domains, contains an autoinhibitor. CDPK isoform AK1 from Arabidopsis was expressed in Escherichia coli as a fusion protein sandwiched between glutathione S-transferase and six consecutive histidines at the N- and C-terminal ends, respectively. This fusion, called AK1-6H, was purified and displayed kinase activity which was stimulated up to 127-fold by Ca2+, with a typical specific activity of 2000 nmol min-1 mg-1, using syntide-2 as peptide substrate. A truncation which deletes the calmodulin like domain, as in mutant delta C-6H, disrupts Ca2+ activation and leaves the enzyme with a basal level of activity. Delta C-6H could be activated 87-fold by preincubation with a purified polyclonal IgG which was raised against a junction domain fusion. A further deletion of the junction domain, as in mutant delta JC, results in a constitutively active enzyme. This indicates that the junction domain in delta C-6H can function as an autoinhibitor. Its function as an autoinhibitor in a full-length enzyme was confirmed by site-specific mutagenesis, as shown by mutant KJM23-6H, which had a six-residue substitution in the junction domain between A422 and A432. Both delta JC and KJM23-6H encoded Ca(2+) independent enzymes which had specific activities greater than 70% that of a fully active AK1-6H and displayed equivalent Km values for ATP and syntide-2. Inhibition studies on delta JC, using peptides based on the autoinhibitory domains of Ca2+/calmodulin-dependent protein kinases, are consistent with a model where the junction domain contains a similar pseudosubstrate-type autoinhibitor. PMID- 8003492 TI - Properties of the arsenate reductase of plasmid R773. AB - Resistance to toxic oxyanions in Escherichia coli is conferred by the ars operon carried on plasmid R773. The gene products of this operon catalyze extrusion of antimonials and arsenicals from cells of E. coli, thus providing resistance to those toxic oxyanions. In addition, resistance to arsenate is conferred by the product of the arsC gene. In this report, purified ArsC protein was shown to catalyze reduction of arsenate to arsenite. The enzymatic activity of the ArsC protein required glutaredoxin as a source of reducing equivalents. Other reductants, including glutathione and thioredoxin, were not effective electron donors. A spectrophotometric assay was devised in which arsenate reduction was coupled to NADPH oxidation. The results obtained with the coupled assay corresponded to those found by direct reduction of radioactive arsenate to arsenite. The only substrate of the reaction was arsenate (Km = 8 mM); other oxyanions including phosphate, sulfate, and antimonate were not reduced. Phosphate and sulfate were weak inhibitors, while the product, arsenite, was a stronger inhibitor (Ki = 0.1 mM). Arsenate reductase activity exhibited a pH optimum of 6.3-6.8. These results indicate that the ArsC protein is a novel reductase, and elucidation of its enzymatic mechanism should be of interest. PMID- 8003491 TI - Pseudosubstrate inhibition of CDPK, a protein kinase with a calmodulin-like domain. AB - Between the catalytic and regulatory domains of calmodulin-like domain protein kinase, CDPK, is a junction domain which has some identity to the autoinhibitory domain of calmodulin-dependent protein kinase type II (Harper, J. F., Sussman, M. R., Schaller, G. E., Putnam-Evans, C., Charbonneau, H., & Harmon, A. C. (1991) Science 252, 951-954). To investigate whether CDPK's junction domain also functions as an autoinhibitory domain, we determined the effect of synthetic peptides, corresponding to sequences within the junction domain, on the activity of native soybean CDPK. Three peptides, corresponding to residues 310-332, 318 332, 302-317, were competitive inhibitors with respect to syntide-2 and had Ki values of 5, 25, and 85 microM, respectively. These peptides were uncompetitive inhibitors with respect to ATP and had Ki values of 24, 220, and 510 microM, respectively. A fourth peptide, CDPK alpha 302-332, inhibited activity by a mixed mechanism with respect to both syntide-2 (Ki = 1.9 microM; K'i = 5.0 microM) and ATP (Ki = 15 microM; K'i = 4.5 microM). Three of the peptides, CDPK alpha 302 332, 310-332, and 318-332, formed complexes with soybean calmodulin during electrophoresis in native polyacrylamide gels and were able to inhibit calmodulin dependent protein kinases. Given the similarity between CDPK's calmodulin-like domain and calmodulin (40% sequence identity), it was possible that these peptides could inhibit activity through interaction with the calmodulin-like domain rather than the catalytic domain. To address this possibility, a cDNA encoding the first 312 residues of soybean CDPK alpha was constructed and expressed in Escherichia coli. This enzyme, which is missing most of the junction domain and all of the calmodulin-like domain, was active in the presence and absence of calcium. Peptide CDPK alpha 310-332 inhibited this truncated enzyme competitively with respect to syntide-2 (Ki = 4 microM). These results show that the junction domain is capable of functioning as an autoinhibitory domain, possibly through a pseudosubstrate site located between residues 310 and 332. PMID- 8003493 TI - Arsenate reductase of Staphylococcus aureus plasmid pI258. AB - Arsenate reductase encoded by Staphylococcus aureus arsenic-resistance plasmid pI258 was overproduced in Escherichia coli and purified. The purified enzyme reduced radioactive arsenate to arsenite when coupled to thioredoxin, thioredoxin reductase, and NADPH. NADPH oxidation coupled to arsenate reduction also required thioredoxin and thioredoxin reductase. Glutaredoxin and reduced glutathione did not stimulate arsenate reduction. NADPH oxidation showed Michaelis-Menten kinetics with a Km of 1 microM AsO4(3-) and an apparent Vmax of 200 nmol/min per mg of protein. At high substrate concentration (above 1 mM AsO4(3-), a secondary rise in the reaction rate was observed, with a Km of 2 mM and an apparent Vmax of 450 nmol/min per mg of protein. This secondary rise also occurred upon addition of phosphate or nitrate (which were not substrates for the enzyme). Arsenite (the product of the enzyme), tellurite, and antimonite [Sb(III)] were inhibitors. Selenate (but not selenite or sulfate) was a substrate for reductase-dependent NADPH oxidation, with an apparent Km of 13 mM SeO4(2-). Arsenate reductase was purified as a monomer of 14.5 kDa, consistent with the DNA sequence. Electrospray mass spectrometry showed two molecular masses of 14,810.5 and 14,436.0 Da, suggesting that 70% of the purified protein lacked the N-terminal three amino acids; HPLC coupled to electrospray mass spectroscopy of protease digest products confirmed this conclusion and verified the entire amino acid sequence. PMID- 8003494 TI - Site-directed mutagenesis of ubiquitin. Differential roles for arginine in the interaction with ubiquitin-activating enzyme. AB - The strict evolutionary conservation of ubiquitin suggests an essential role for each residue in the folding, stability, or function of the protein but precludes identification of such contributions through interspecies comparison of ubiquitin sequences. However, site-directed mutagenesis potentially allows assignment of specific function(s) for each residue. The four arginines present on ubiquitin at positions 42, 54, 72, and 74 were independently mutated to leucine and their effects on the interaction of the resulting polypeptides with ubiquitin activating enzyme (E1) were characterized. All of the mutants except UbR54L exhibited altered kinetics for E1-catalyzed ATP:PPi exchange compared to wild type ubiquitin. In addition, the UbR72L mutant altered the mechanism of E1 from strictly order addition of substrates to random addition with respect to ATP and ubiquitin. Values for the intrinsic Kd of ubiquitin binding were determined by coupling the net forward reaction of E1 to the E232K-catalyzed conjugation of histone H2B. Only R54 and R72 residues participate in the initial binding of free ubiquitin, resulting in a 6- or 58-fold increase in Kd for UbR54L or UbR72L, respectively, compared to wild type. More significant effects of the UbR42L and UbR72L mutants were observed for binding of their respective ubiquitin adenylate intermediates within the E1 active site. Wild-type ubiquitin adenylate binds to E1 with an estimated Kd < or = 8 x 10(-12) M while intermediates formed with UbR42L or UbR72L each bind with ca. 10(3)-fold lower affinity, representing a destabilization of > or = 7 kcal/mol.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8003495 TI - The energetic linkage of GTP hydrolysis and the synthesis of activated sulfate. AB - ATP sulfurylase, from Escherichia coli K-12, catalyzes both the hydrolysis of GTP and the synthesis of activated sulfate (APS). This paper describes the energetic linkage of these reactions and the events that couple them. Steady-state and single-turnover experiments suggest that the binding of GTP inhibits APS production and that the hydrolysis of GTP is required to generate the enzyme form(s) that produces APS. It is this progression from the inhibitory, E-GTP, to the productive, E-GDP, complexes in the cycle of APS synthesis that energetically links these two reactions. This model stands in contrast to other GTPase/target systems in which the binding of GTP alone is sufficient to catalyze multiple turnovers of the target reaction. The stoichiometry of GTP hydrolysis to APS synthesis is 1:1, and equilibrium measurements show that -9.1 kcal/mol, produced by the hydrolysis of GTP, is used to thermodynamically drive production of APS and PPi. These findings establish the mechanism of energy transfer in this novel GTPase/target system, and substantially alter our understanding of the energetics of sulfate activation, an essential step in the metabolic assimilation of sulfur. PMID- 8003496 TI - The solution structure of the hairpin formed by d(TCTCTC-TTT-GAGAGA). AB - The 15-residue oligonucleotide d(TCTCTC-TTT-GAGAGA) forms a hairpin structure with a loop of three thymidine residues at neutral pH or above. The three dimensional solution structure of this oligonucleotide has been determined by means of two-dimensional nuclear magnetic resonance methods. Interproton distance constraints derived from NOEs, in combination with torsion angle constraints obtained from J-coupling constants were used in the variable target function program DIANA to derive the hairpin structure. It was found that hairpins with two different loop conformations fit the NMR data, i.e. an equilibrium between these two conformational states can only fully explain the NOE data available. In one state, loop residue T7 is turned into the minor groove, while in the second state residue T8 is in the minor groove. In both conformations the phosphate backbone changes its direction by 180 degrees between residues T9 and G10. Concomitantly, torsion angles zeta of T9 and alpha of G10 both adopt a gauche(+) conformation and gamma of residue G10 adopts a trans conformation to induce this complete change in the direction of the backbone. PMID- 8003498 TI - Relationship of phospholipid distribution to shape change in Ca(2+)-crenated and recovered human erythrocytes. AB - Echinocytosis induced by elevation of intracellular Ca2+ in human erythrocytes can be reversed by removal of the cation. Using back-extraction of radiolabeled dilauroyl phospholipid analogs which had been incorporated into the cell membrane, we examined the relationship between this reversible shape transformation and phospholipid distribution. Upon Ca2+ crenation of cells, surface exposure of phosphatidylserine and phosphatidylethanolamine was observed simultaneously with inward diffusion of phosphatidylcholine. Removal of Ca2+ allowed resequestration of exposed phosphatidylserine to the membrane inner monolayer, but randomized phosphatidylethanolamine and phosphatidylcholine were not redistributed to their original states. Both shape reversion and retranslocation of phosphatidylserine were reversibly inhibited vanadate. On the other hand, the cell shape recovery was found to be independent of membrane skeleton and phosphoinositide metabolism and was supported by ATP resynthesis only under conditions where the aminophospholipid translocator is active. Other Ca(2+)-mediated biochemical changes, such as generation of diacylglycerol and fatty acids, were found to have no effect on Ca2+ crenation or its reversal, or upon transbilayer distribution of any phospholipid. These findings suggest that Ca2+ induces phospholipid redistribution, possibly by direct interaction with the lipid bilayer and, further, that metabolic recovery from Ca2+ crenation reflects selective retransport of phosphatidylserine to the membrane inner monolayer. PMID- 8003497 TI - X-ray crystal structure of gamma-chymotrypsin in hexane. AB - Crystals of gamma-chymotrypsin grown in aqueous solution were soaked in n-hexane, and the structures of both the soaked and the native crystals were determined to 2.2-A resolution. Seven hexane molecules and 130 water molecules were found in the hexane-soaked crystals. Two of the seven hexane molecules are found near the active site, and the rest are close to hydrophobic regions on or near the surface of the enzyme. In the hexane structure, water molecules that were not observed in the native structure form a clathrate around one of the hexane molecules. Only 97 water molecules were found in the native structure. The temperature factors for atoms in the hexane environment are lower than those in the aqueous environment. There are significant changes between the two structures in the side chains of both polar and neutral residues, particularly in the vicinity of the hexane molecules. These changes have perturbed the hydrogen-bonding patterns. The electron density for the peptide bound in the active site has been dramatically altered in hexane and appears to be tetrahedral at the carbon that is covalently bound to Ser 195. The crystalline enzyme retains its active conformation in the nonpolar medium and can catalyze both hydrolysis and synthesis reactions in hexane. PMID- 8003499 TI - Far-UV circular dichroism reveals a conformational switch in a peptide fragment from the beta-sheet of hen lysozyme. AB - The conformation of a 20-residue synthetic peptide corresponding to the antiparallel triple-stranded beta-sheet in hen egg white lysozyme (residues 41 60) has been studied by circular dichroism (CD) and size-exclusion chromatography. In aqueous solution the conformation of the peptide is strongly pH dependent. At pH values below 4.0 and 25 degrees C, the far-UV CD spectrum of the peptide resembles that expected for a predominantly beta-sheet structured (low-pH form), while at pH values exceeding 4.0 the spectrum changes to that of a predominantly unstructured conformation (high-pH form). The far-UV CD spectrum of the high-pH form (pH 6.8) is not affected by changes in the concentration of the peptide and by changes in temperature and ionic strength. By contrast, the far-UV CD spectrum of the low-pH form (pH 2.0) is concentration and temperature dependent but is not affected by ionic strength. Size-exclusion chromatography trimers and higher oligomers and that the monomeric form of the peptide at low pH is predominantly random in nature. Significant helical structure was induced in the high-pH form of the peptide by both trifluoroethanol (TFE) and methanol; by contrast, the conformation of the low-pH form of the peptide was not changed with concentrations of methanol up to 50% (v/v), although in the presence of TFE a state displaying significant helical character was induced. During the transition an intermediate which also displays significant beta-sheet character but which has a distinct CD spectrum is populated. The relevance of this study to the folding pathway of the intact protein is discussed. PMID- 8003500 TI - Kinetics of biotinyl-5'-adenylate synthesis catalyzed by the Escherichia coli repressor of biotin biosynthesis and the stability of the enzyme-product complex. AB - The Escherichia coli repressor of biotin biosynthesis is both a biotin ligase and the repressor of transcriptional initiation at the biotin biosynthetic operon. The small molecule, biotinyl-5'-adenylate (bio-5'-AMP), is the intermediate in the biotin ligation reaction and the positive allosteric effector for sequence specific DNA binding by BirA. Synthesis of the adenylate from the substrates biotin and ATP is catalyzed by BirA. Although BirA and other biotin holoenzyme synthetases have been the subject of biochemical studies, no direct measurements of the bio-5'-AMP synthesis reaction have been reported. No information relating to the mechanism and kinetic parameters governing adenylate synthesis is available. In addition to this lack of kinetic information, the thermodynamic stability of the BirA-bio-5'-AMP complex is not known. Since the BirA-adenylate complex plays a pivotal role in the biotin regulatory system, both the kinetic and thermodynamic information are essential to a quantitative understanding of the system. We have developed a method for measuring the time course of bio-5' AMP synthesis. The results of these measurements indicate that the time course is characterized by an initial burst followed by a slow linear phase. The burst corresponds to the rapid synthesis of 1 mol of product per mole of enzyme, and the rate of the slow linear phase is limited by the release of product from the enzyme.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8003501 TI - Subdomain folding of the coiled coil leucine zipper from the bZIP transcriptional activator GCN4. AB - One popular model for protein folding, the framework model, postulates initial formation of secondary structure elements, which then assemble into the native conformation. However, short peptides that correspond to secondary structure elements in proteins are often only marginally stable in isolation. A 33-residue peptide (GCN4-p1) corresponding to the GCN4 leucine zipper folds as a parallel, two-stranded coiled coil [O'Shea, E.K., Klemm, J.D., Kim, P.S., & Alber, T.A. (1991) Science 254, 539-544]. Deletion of the first residue (Arg 1) results in local, N-terminal unfolding of the coiled coil, suggesting that a stable subdomain of GCN4-p1 can form. N- and C-terminal deletion studies result in a 23 residue peptide, corresponding to residues 8-30 of GCN4-p1, that folds as a parallel, two-stranded coil with substantial stability (the melting temperature of a 1 mM solution is 43 degrees C at pH 7). In contrast, a closely related 23 residue peptide (residues 11-33 of GCN4-p1) is predominantly unfolded, even at 0 degrees C, as observed previously for many isolated peptides of similar length. Thus, specific tertiary packing interactions between two short units of secondary structure can be energetically more important in stabilizing folded structure than secondary structure propensities. These results provide strong support for the notion that stable, cooperatively folded subdomains are the important determinants of protein folding. PMID- 8003503 TI - Mutation of chlorophyll ligands in the chlorophyll-binding CP47 protein as studied in a Synechocystis sp. PCC 6803 photosystem I-less background. AB - Site-directed mutations have been introduced to replace conserved histidine residues in the chlorophyll-binding protein CP47 of photosystem II (PS II) in a PS I-less/apcE-background strain of the cyanobacterium Synechocystis sp. PCC 6803. In thylakoids isolated from such a system, the degree of loss of the 695-nm fluorescence emission maximum at 77 K compared to that at 685 nm generally was consistent with the decrease in oxygen evolution rates measured at saturating light intensity. Taking into account that in the absence of CP47 and PS I some chlorophyll remains detectable in cells, the relative 695-nm fluorescence emission and the rate of oxygen evolution also correlate with the relative amount of chlorophyll per cell and with the number of PS II reaction centers on a chlorophyll basis. Interestingly, the 77 K fluorescence excitation spectra monitoring 695-nm emission of thylakoids from the CP47 His-to-Tyr mutants in a photosystem I-less/apcE-background showed increases in the 413- and 531-nm absorption regions, compared to spectra of thylakoids from the background strain. These wavelengths coincide with absorption maxima of pheophytin. No increase in the 531-nm excitation band was observed in thylakoids from mutants lacking PS II or with a His-to-Asn mutation. These results are interpreted to indicate that replacement of conserved histidine residues by tyrosine in CP47 leads to the loss of Mg2+ from chlorophyll, resulting in the formation of pheophytin, or to the binding of pheophytin (rather than chlorophyll) at a particular pigment-binding site of CP47 during biogenesis and assembly of the protein. It was observed that the light-harvesting efficiency of CP47 His mutants was lower judging from the light intensity dependence of electron transport and analysis of fluorescence decay kinetics. This suggests that the presence of pheophytin in the antenna decreases antenna efficiency. PMID- 8003502 TI - Noncovalent binding of heme induces a compact apocytochrome c structure. AB - Mitochondrial holocytochrome c contains heme that is covalently attached to the protein in a reaction catalyzed by the enzyme cytochrome c heme lyase. In the absence of heme, apocytochrome c, the precursor to holocytochrome c, is unfolded. We find that purified apocytochrome c binds noncovalently to heme. Binding is accompanied by changes in the optical absorption spectrum of heme and by quenching of the tryptophan fluorescence of the protein. The affinity of apocytochrome c for heme, as well as the stoichiometry of binding, appears to depend on whether or not cyanide is present and on the oxidation state of heme. Under reducing conditions, in the presence of cyanide, the association appears to be 1:1, with a binding constant of about 10(7) M-1. Under oxidized conditions, there may be multiple hemes bound per molecule of apocytochrome c. Upon binding to heme, apocytochrome c exhibits a mobility similar to that of holocytochrome c in gel filtration chromatography and velocity gradient ultracentrifugation, indicating that the heme-protein complex adopts a structure that is almost as compact as that of holocytochrome c. Changes in the circular dichroism spectrum of apocytochrome c are consistent with an increase in the alpha-helical content of the protein on binding heme. The compact structure of the noncovalent heme apocytochrome c complex may represent an intermediate in the de novo folding of cytochrome c. PMID- 8003504 TI - Interactions of the beta-ionone ring with the protein in the visual pigment rhodopsin control the activation mechanism. An FTIR and fluorescence study on artificial vertebrate rhodopsins. AB - The photoreactions of rhodopsin regenerated with three 9-cis retinal analogs, modified at or in the vicinity of the beta-ionone ring (namely 5,6-epoxy, 7,8 diH, diethyl-acyclic) have been investigated by UV-vis and FTIR difference spectroscopy. In parallel, the ability to catalyze the GDP-->GTP exchange of G protein (transducin) has been monitored by time-dependent fluorescence spectroscopy. The first photoproduct obtained with all three pigments at liquid nitrogen temperature is a blue-shifted intermediate (BSI), followed by a lumi like intermediate at 170 K. For the 5,6-epoxy-ISO and 7,8-diH-ISO pigment we obtain two further intermediates similar to the META-I and META-II states of native RHO. For the diethyl-acyclic-ISO pigment only one further intermediate can be stabilized at 280 K. As compared to META-II the respective photoproduct exhibits striking differences. The latter two pigments have also been investigated in the solubilized lipid-free state (detergent: dodecyl maltoside) at 280 K. For the 5,6-epoxy-ISO pigment, the UV-vis, FTIR, and activation data agree with the formation of a META-II-like photoproduct (81% activation). Less META-II formation is observed for the 7,8-dihydro-ISO pigment in membranes (65% activation), but full formation in detergent (100% activation). Neither the membrane-bound nor the solubilized diethyl-acyclic-ISO pigment forms a META-II like intermediate (18% and 0% activation, respectively). Therefore, we conclude that the substitution of the beta-ionone ring by two ethyl groups abolishes steric interactions with the protein, which are essential for META-II formation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8003505 TI - Characterization of recombinant horseradish peroxidase C and three site-directed mutants, F41V, F41W, and R38K, by resonance Raman spectroscopy. AB - Resonance Raman spectra are reported for recombinant horseradish peroxidase C (HRP-C*) and three protein variants prepared by in vitro refolding after Escherichia coli expression. The spectra of their FeII and FeIII forms and of their complexes with benzohydroxamic acid (BHA) were recorded at neutral pH. The residues mutated were on the distal [Phe41-->Trp or Val (F41W, F41V) and Arg38- >Lys (R38K)] side of the heme. The spectra give information on the spin and ligation states via the frequencies of the core size marker bands. No detectable modification in the enzyme structure or in the heme group has been observed in the wild-type recombinant HRP-C*. The FeIII forms of both the recombinant and the plant proteins show the coexistence of a 5-(5-cHS) and a 6-coordinate high-spin (6-cHS) heme, characterized by the anomalous frequencies of certain bands, namely, v3 and v10, which we attribute to a different degree of distortion of the heme planarity with respect to other heme proteins and model compounds, resulting from external forces such as steric contacts within the protein. This effect is partially relieved upon complexation with BHA or as a result of mutation. F41W and F41V are characterized by an increase in a 6-cHS form at the expense of the 5 cHS species, and the R38K by an increase in both the 6-c high-(HS) and low-spin (LS) hemes. The 6-cHS and -LS species are characterized by normal core size marker band frequencies. The FeII-His RR band is at 243 cm-1 in HRP-C*, the high frequency value being due to hydrogen-bonding interactions between the proximal His170 N delta and the carboxylate acceptor group on Asp247. Mutation at position 38 causes a downshift of 3 cm-1 in the v(Fe-Im) stretching mode, suggesting a weakening of the Fe-Im bond strength. By comparing the results obtained with HRP C* mutants with those previously reported for the corresponding cytochrome c peroxidase (CCP) mutants, it appears that the distal heme pocket architecture is significantly different in the two peroxidases, although the hydrogen-bonding network coupling the distal and the proximal sides of the heme appears to be conserved. Mutations on the distal side dramatically affect the capability of the protein to bind BHA. F41W and R38K mutants do not bind the substrate, whereas the F41V variant shows a 2-fold increase in affinity.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8003506 TI - Energetics of catalysis by ribonucleases: fate of the 2',3'-cyclic phosphodiester intermediate. AB - Ribonucleases catalyze the hydrolysis of the P-O5' bond in RNA. This reaction occurs in two steps: transphosphorylation of RNA to a 2',3'-cyclic phosphodiester intermediate and hydrolysis of this intermediate to a 3'-phosphomonoester. 31P NMR spectroscopy was used to monitor the accumulation of the 2',3'-cyclic phosphodiester intermediate during the transphosphorylation and hydrolysis reactions catalyzed by various ribonucleases and by small molecules. The intermediate was found to accumulate during catalysis by monomeric bovine pancreatic ribonuclease A (RNase A), a dimer and a trimer of RNase A, bovine seminal ribonuclease, RNase T1, barnase, and RNase 1. These enzymes, which are of widely disparate phylogenetic origin, released rather than hydrolyzed most of the intermediate formed transphosphorylation of RNA. In contrast, the intermediate did not accumulate during catalysis by hydroxide ion or imidazole buffer. In the presence of these small molecules, hydrolysis is faster than transphosphorylation. A trapping experiment was used to assess the throughput of the reaction catalyzed by RNase A. [5,6-3H]Uridylyl-(3'-->5')adenosine was incubated with RNase A in the presence of excess unlabeled uridine 2',3'-cyclic phosphodiester, which dilutes the specific radioactivity of any released cyclic intermediate. Only 0.1% of the RNA substrate was found to be both transphosphorylated and hydrolyzed without dissociating from the enzyme. These results suggest that ribonucleases have evolved primarily to catalyze RNA transphosphorylation and not RNA hydrolysis. PMID- 8003507 TI - Characterization of the three tyrosine residues of delta 5-3-ketosteroid isomerase by time-resolved fluorescence and circular dichroism. AB - delta 5-3-Ketosteroid isomerase (EC 5.3.3.1) of Pseudomonas testosteroni converts delta 5-3-ketosteroids to delta 4-3-ketosteroids via an enolic intermediate. Site specific mutagenesis has identified Tyr-14 and Asp-38 as the catalytically essential general acid and base, respectively. Three tyrosine residues (Tyr-14, Tyr-55, and Tyr-88) are the only significant fluorophores in the wild-type isomerase. Recent studies of the steady-state fluorescence of the wild-type enzyme and all six mutant enzymes in which one or two tyrosine residues have been mutated to phenylalanine show that the fluorescence intensity of Tyr-14 is very high, that of Tyr-88 is very low, and that of Tyr-55 is intermediate and comparable to that of N-acetyltyrosine amide in solution (Li, Y.-K., Kuliopulos, A., Mildvan, A.S., & Talalay, P. (1993) Biochemistry 32, 1816-1824). Extension of these experiments by time-resolved fluorescence and fluorescence anisotropy measurements demonstrates that Tyr-14, which is in a hydrophobic environment, has an unusually long fluorescence lifetime (4.6 ns) as compared to Tyr-55 (2.0 ns) or Tyr-88 (0.8 ns) and to most protein tyrosine residues (0.2-2 ns). The Forster distances obtained from the absorption and emission of these tyrosines predict that total quenching of Tyr-14 fluorescence by Tyr-55, and to a lesser degree by Tyr-88, would occur if their orientations were favorable.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8003509 TI - Characterization of an ATP-stimulatable Ca(2+)-independent phospholipase A2 from clonal insulin-secreting HIT cells and rat pancreatic islets: a possible molecular component of the beta-cell fuel sensor. AB - Isolated pancreatic islets from rats and humans express a plasmalogen-preferring ATP-stimulatable, Ca(2+)-independent phospholipase A2 (ASCI-PLA2) enzyme which participates in the glucose-stimulated hydrolysis of arachidonate from membrane phospholipids and in insulin secretion. Here we report that clonal insulin secreting HIT beta-cells contain substantial amounts of endogenous plasmalogens and express a similar ASCI-PLA2 activity with the following properties: (1) Enzymatic activity as well as glucose-induced eicosanoid release and insulin secretion are inhibited by a mechanism-based suicide substrate directed towards ASCI-PLA2. (2) HIT cell ASCI-PLA2 is selectively activated and protected against thermal denaturation by ATP. (3) The magnitude of ASCI-PLA2 activation by the nonhydrolyzable ATP analog AMP-PCP is similar to that by ATP. (4) The ATP concentrations required to activate ASCI-PLA2 fall within physiologic ranges in the presence of Mg2+. (5) ADP induces a concentration-dependent attenuation of the activation of ASCI-PLA2 by ATP. HIT cell ASCI-PLA2 exhibited an apparent isoelectric point of 7.5 on chromatofocusing analysis and was quantitatively adsorbed to an ATP-agarose matrix and selectively desorbed from this column by ATP. Mono-Q anion-exchange analysis of the active ATP-agarose eluant yielded a peak of ASCI-PLA2 activity associated with a single protein band with an apparent molecular mass of 40 kDa. Similar chromatographic behavior of the rat pancreatic islet ASCI-PLA2 activity was observed during sequential ATP-agarose and Mono-Q anion-exchange steps. These results indicate that HIT cells express an ASCI-PLA2 similar to the analogous islet enzyme and suggest that expression of this enzyme and of its preferred plasmalogen substrates may be a general property of insulin secreting beta-cells. PMID- 8003508 TI - Alzheimer beta-amyloid peptide 25-35: electrostatic interactions with phospholipid membranes. AB - The role of lipids in the aggregation of three Alzheimer model peptides was investigated with circular dichroism spectroscopy and high-sensitivity titration calorimetry under conditions of low ionic strength. In solution, the peptides beta AP(25-35)OH and beta AP(25-35Nle)NH2 exhibit a reversible random-coil<- >beta-sheet (or beta-structured aggregate) transition. Addition of lipid vesicles containing negatively charged lipids shifts the random-coil<-->beta-sheet equilibrium almost completely toward beta-sheet structure, which can be explained by the specific conditions created at the membrane surface: the cationic peptides are attracted to the negatively charged membrane, and the increase in peptide concentration together with the partial alignment of the peptide molecules then facilitates beta-sheet formation. The third peptide, beta AP-(25-35)NH2, also binds to the lipid membrane but was found to adopt an essentially random-coil structure, both with and without lipids. A quantitative characterization of the binding equilibrium was possible with high-sensitivity titration calorimetry. All three peptides exhibited exothermic binding enthalpies which varied between delta H approximately -2 kcal/mol for beta AP(25-35)OH and -8 kcal/mol for beta AP(25 35)NH2. The apparent binding constants, calculated with bulk concentrations, were large and varied between 500 and 5 x 10(4) M-1, depending on the experimental conditions. However, after correction for electrostatic charge effects using the Gouy-Chapman theory, the intrinsic binding constants were found to be constant and much smaller with K approximately 2-10 M-1.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8003510 TI - Activation of overexpressed receptors for insulin and epidermal growth factor interferes in mitogenic signaling without affecting the activation of p21ras. AB - Activated receptors with a tyrosine kinase activity induce a variety of responses like changes in the differentiation and mitogenic status of cells. These responses are mediated in part by p21ras. Some of these activated receptors induce in certain cell types a pronounced, but transient, increase in Ras-GTP. We have stimulated cells with insulin, epidermal growth factor (EGF), and fetal calf serum (FCS), and the mitogenic response, as reflected by stimulation of [3H]thymidine incorporation, was compared with the magnitude of the transient increase in Ras-GTP levels. Cell lines were used that expressed both physiological and elevated numbers of p21ras and receptors for insulin and EGF, respectively. In all the examined cell lines 9% FCS did not induce a marked increase in Ras-GTP despite its high mitogenic potency. Pronounced increases in Ras-GTP levels were observed in insulin-stimulated CHO cells which overexpress insulin receptors whereas in the parental CHO cells only a small increase is seen. Insulin (1 microM) and FCS (9%) stimulate [3H]thymidine incorporation in parental CHO cells to a similar high level whereas in insulin receptor overexpressing CHO cells the maximum of insulin-stimulated [3H]thymidine incorporation is only 55% of the level reached by 9% FCS. In those cells the maximum is already reached at low (1 nM) insulin concentrations. Remarkably, at higher insulin concentrations stimulation of [3H]thymidine incorporation starts to decrease strongly despite the fact that the magnitude of the transient increase in Ras-GTP and subsequent MAPkinase activation increases. Similarly, when EGF receptors are overexpressed in Rat-1 cells, the mitogenic response is also decreased at higher EGF concentrations.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8003512 TI - Receptor-binding affinities of human epidermal growth factor variants having unnatural amino acid residues in position 23. AB - Ile-23 of human epidermal growth factor (hEGF) has been indicated, by mutagenesis and NMR studies, to be directly recognized by the receptor. In the present study, an unnatural phenylalanine analog, either 2-azaphenylalanine (2aF), 3 azaphenylalanine (3aF), 4-azaphenylalanine (4aF), or 4-fluorophenylalanine (4fF), was incorporated by an in vivo protein synthesis system into position 23 of [Phe23]hEGF, which retains appreciable receptor-binding affinity (about 20% of the wild type). We compared the receptor-binding affinities of the variants with that of [Phe23]hEGF and found that substitution of Phe-23 with 2aF or 3aF raised the affinity, while substitution with 4aF or 4fF remarkably reduced the affinity. The tertiary structure of [Phe23]hEGF was not significantly affected by the substitution of Phe-23 with 2aF, as shown by the two-dimensional nuclear magnetic resonance analysis. In addition, the substitution of residue 23 with His or Tyr produced an hEGF variant with a slightly higher receptor-binding affinity than that of [Phe23]hEGF. Our results suggest that the receptor has an asymmetric hydrophobic pocket for recognition of the side chain in position 23 of hEGF. Furthermore, on the receptor surface, this pocket seems to be adjacent to a less hydrophobic region with a hydrogen-bond acceptor and donor. Thus, the use of unnatural amino acids in addition to the 20 natural ones allows analyses of the structure-function relationship of a protein at a higher resolution than conventional site-directed substitution by only natural amino acid residues. PMID- 8003511 TI - Parathyroid hormone-related protein: evidence for isoform- and tissue-specific posttranslational processing. AB - Parathyroid hormone-related protein (PTHrP) is expressed by malignant tumors and leads to the syndrome of humoral hypercalcemia of malignancy. It is also expressed by a wide variety of nonmalignant tissues, in which it appears to play distinct paracrine and/or autocrine roles. The human PTHrP gene encodes three cDNA-predicted initial translational products of 139, 141, and 173 amino acids. Most human cell lines contain mRNAs encoding all three PTHrP isoforms. The physiological rationale for the existence of these three highly similar transcripts is unknown. In order to determine whether the protein products derived from these three transcripts differ, we transfected Chinese hamster ovary (CHO) cells and rat insulinoma (RIN) cells individually with cDNAs encoding human PTHrP(1-139), PTHrP(1-141), and PTHrP(1-173). Cell extracts and conditioned medium were then chromatographed using reversed-phase HPLC and analyzed using region-specific PTHrP immunoassays. As we had previously observed in SKRC-1 (renal cell carcinoma) and RIN(1-141) cells, multiple amino-terminal PTHrP species as well as a separate midregion PTHrP species were identified in all six cell lines. In addition, both CHO and RIN cell lines transfected with the PTHrP(1 139) construct contained a previously unrecognized carboxy-terminal fragment that reacted with a PTHrP(109-138) antiserum. This carboxy-terminal fragment was physically distinct from the midregion fragment discovered earlier and was also present in conditioned medium, indicating that it is a secretory form, rather than a biosynthetic intermediate or a degradation product.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8003513 TI - Identification of a putative membrane-inserted segment in the alpha-toxin of Staphylococcus aureus. AB - To gain a fuller understanding of the regions of the Staphylococcus aureus alpha toxin important in pore formation, we have used Forster dipole-dipole energy transfer to demonstrate that a central glycine-rich region of alpha-toxin (the so called "hinge" region) inserts deeply into the bilayer on association of toxin with liposomes. Mutant alpha-toxins with unique cysteine (C) residues at positions 69 and 130 [Palmer, M., et al. (1993) J. Biol. Chem. 268, 11959) were reacted with the C-specific fluorophore acrylodan, which acted as an energy donor. The chosen acceptor was N-(7-nitrobenz-2-oxa-13- diazol-4-yl)-1,2 bis(hexadecanoyl)-sn-glycero-3-phosphoethanolamin e (NBD-PE). Measurement of the degree of donor quenching with increasing NBD-PE in the inner bilayer leaflet enables the distance of closest approach between donor and acceptor to be estimated. For toxin labeled with acrylodan at position 130 (in the hinge region), this distance is approximately 5 +/- 2 A, showing that the probe is close to the inner surface of the liposomes. A second probe labeled at position 69 (in the N-terminal domain) shows negligible energy transfer, indicating a distance of closest approach > 40 A. This implies that this N-terminal region remains "outside" the liposome. We propose a model in which the central region of the alpha-toxin inserts into the membrane and possibly participates in forming the wall of the pore. PMID- 8003514 TI - Crosstalk between domains in the regulatory subunit of cAMP-dependent protein kinase: influence of amino terminus on cAMP binding and holoenzyme formation. AB - The regulatory (R) subunit of cAMP-dependent protein kinase os an asymmetric multidomain protein with a dimerization domain at the N-terminus, an autoinhibitors site, and two cAMP binding domains at the C-terminus. Activation of the tetrameric holoenzyme is mediated by the cooperative binding of cAMP to the two cAMP binding sites. To better understand how the various domains influence each other, the N-terminus (delta 1-91) up to the autoinhibitor site was deleted. Not only did this monomeric deletion mutant, purified from Escherichia coli, still bind cAMP and the catalytic (C) subunit with high affinity, holoenzyme formation was actually accelerated by at least 50-fold. MgATP also was not required for rapid reassociation of (delta 1-91)R(cAMP)2 and C. The Kd(cAMP) and the Ka(cAMP) were similar to those for holoenzyme formed with full-length R; however, cooperatively was lost. Thus the N-terminus, either by inter- or intraprotomer contacts, not only impedes holoenzyme formation but also influences the cooperative binding of cAMP. The 1-91 deletion also renders the remaining fragment resistant to proteolytic degradation. Finally, unlike full length R, the mutant protein can migrate freely into the nucleus. Surface plasmon resonance studies for the first time enabled direct measurements of the association and dissociation rate constants both for the intact R and for (delta 1-91)R. Both displayed very fast on-rates (1 x 10(-5) M-1 s-1 and 1.1 x 10(-5) M 1 s-1, respectively) and extremely slow off-rates (2.3 x 10(5) M-1 and 4.3 x 10(5) M-1, respectively). Thus, unlike the heat-stable protein kinase inhibitor, the region preceding the autoinhibitor site in R does not contribute in a quantitatively significant way to the high-affinity binding of C. PMID- 8003515 TI - A health care comparison of the United States and England. PMID- 8003516 TI - Virtual reality. PMID- 8003517 TI - Women's anger: facts and myths. PMID- 8003518 TI - Bridging the communication gap: the nursing connection. PMID- 8003519 TI - 'Just think of it as tomorrow'. News for the world of education. PMID- 8003520 TI - 'Organic phase buffers' control biocatalyst activity independent of initial aqueous pH. AB - Combinations of triisooctylamine with its hydrochloride, or of triphenylacetic acid with its Na+ salt, can function as buffers for use during biocatalysis in organic media. They can control the pH of an adjacent aqueous phase, even though both forms of each buffer remain in the organic phase. With 0.1 M aqueous NaCl, the mid-point pH values obtained with the two buffer systems are around pH 4.5 and 7.0, respectively. The activity of an immobilized subtilisin Carlsberg shows a strong dependence on the ratio of the two forms of the triphenylacetic acid buffer system. Without the buffer, the rate shows the normal dependence on the pH of the aqueous solution before drying; however, this is almost eliminated if the buffer is used. The amine buffer system can similarly affect the activity of an immobilized Rhizomucor miehei lipase. PMID- 8003521 TI - High-pressure effects on beta-lactoglobulin interactions with ligands studied by fluorescence. AB - The effects of pressure (0.1 MPa to 400 MPa) on intrinsic fluorescence of beta lactoglobulin and on its binding of retinol and cis-parinaric acid have been studied at neutral and acid pHs. In neutral pH, fluorescence emission spectra of beta-lactoglobulin tryptophanes are characterized by an irreversible 14 nm red shift indicating pressure-induced folding changes. The intensity of the fluorescence of retinol in beta-lactoglobulin-retinol complex is enhanced by a pressure increase up to 150 MPa. It decreases at higher pressures and disappears altogether at 300 MPa. beta-Lactoglobulin-retinol complex does not reassociate after decompression at neutral pH. At acid pH condition, the fluorescence quenching by pressure of beta-lactoglobulin tryptophans is coupled with a 2 nm spectral shift and is fully reversible demonstrating almost complete restoration of globulin folding. The evolution of retinol fluorescence in beta-lactoglobulin retinol complex is also entirely reversible between 0.1 MPa and 400 MPa and the complex never dissociates in the studied pressure range. beta-lactoglobulin-cis parinaric acid complexes at neutral and acid pH values dissociate irreversibly at 200 MPa and 350 MPa, respectively. PMID- 8003522 TI - Heterogeneities in ferritin dimers as characterized by gel filtration, nuclear magnetic resonance, electrophoresis, transmission electron microscopy, and gene engineering techniques. AB - To understand the mechanism underlying the preferential dimerization of ferritin shells, we studied monomers and dimers from both horse spleen and recombinant horse L-apoferritin by using gel filtration, nuclear magnetic resonance, electrophoresis, transmission electron microscopy, and gene engineering techniques. Our study of the kinetics of dimer-monomer dissociation that is produced by heating revealed the presence of at least two types of dimers, namely, weakly and strongly linked dimers with activation energies of 124 +/- 14 and 157 +/- 16 kJ/mol, respectively. Our study using thiol reagents indicated that the dimerization in horse spleen ferritin is partially mediated by disulfide bridges being formed between H-chains. Our analysis of the components that resulted from the dimer-monomer dissociation further clarified that these dimers form interdigitation structures. In summary, five types of dimers were identified in horse spleen apoferritin: reversible dimers with very weak interaction, non sulfide dimers with weak interaction, non-sulfide dimers with strong interaction, disulfide dimers linked only by disulfide bridges, and disulfide dimers linked by disulfide bridges and having other interactions. PMID- 8003523 TI - The soluble but not mitochondrially bound hexokinase is a substrate for the ATP- and ubiquitin-dependent proteolytic system. AB - Intracellular protein degradation is highly selective, however, the mechanism(s) underlying this selectivity are not fully understood. We have previously shown that purified rabbit hexokinase type I, an enzyme present in mammalian brain both in soluble and mitochondrial bound form, is conjugate to ubiquitin and then degraded by a rabbit reticulocyte fraction II. In the present study we report that the mitochondrial bound hexokinase is stable for several hours in the same proteolytic system both in the presence or absence of ATP. E1, E2 and E3, the enzymes of the ubiquitin conjugating system, are able to incorporate 125I- or biotin-labelled ubiquitin in an ATP-dependent manner in soluble hexokinase as well as in a number of mitochondrial proteins. Furthermore, the mitochondria by themselves have a pronounced ATP-dependent ability to conjugate 125I-ubiquitin. However, Western blotting experiments, using a specific antibody against hexokinase, or against ubiquitin, showed that the mitochondrial bound enzyme is neither ubiquitinated nor degraded. This result has been confirmed by purification of bound hexokinase from the brain mitochondrial fraction or following the incubation of intact mitochondria with ATP, 125I-ubiquitin and E1, E2 and E3. Thus, mitochondrial bound hexokinase is not recognized by the ubiquitin conjugating system while the soluble enzyme is conjugate to ubiquitin and then degraded. Furthermore, the soluble hexokinase from rabbit brain was isolated by immunoaffinity chromatography and shown to be recognized by an anti ubiquitin antibody. These results suggest that the intracellular distribution of protein is an important feature of a protein which determines its susceptibility to ubiquitin-dependent degradation. PMID- 8003524 TI - Stabilized structure of the presynaptic (Y2) receptor-specific neuropeptide Y analog N-acetyl[Leu-28,Leu-31]NPY(24-36). AB - Neuropeptide Y analog N-acetyl[Leu-28,Leu-31]NPY(24-36)-amide binds specifically to prejunctional or Y2 receptors acting to inhibit neurotransmitter release. The structure of this biologically active mutant was studied by two-dimensional proton nuclear magnetic resonance spectroscopy. Assignments of all backbone and side chain hydrogens were made by using totally correlated spectroscopy (TOCSY) experiments providing through-bond 1H-1H connectivities, and nuclear Overhauser effect spectroscopy (NOESY), which provided through-space and sequential backbone connectivities. Structure analysis of the peptide was performed using distance geometry and dynamic simulated annealing revealing the presence of a helical structure exhibiting an amphiphilic character and slight constriction in the segment 24-29. PMID- 8003525 TI - Modes of association of concanavalin A with alpha-D-glycosides. AB - Complexes of Con A with alpha-D-glycosides were studied using 1H-NMR, ESR and fluorescence methods. Correlation times, tau c, for the interaction of the aglycon protons with the manganese ion, present at the S1 site of the protein, were calculated from T1 measurements at two frequencies. The protons of aromatic aglycons have tau c values comparable to the rotational correlation time of the protein molecule, whereas those of non-aromatic aglycons have tau cs 10 to 100 times lower. The correlation times were combined with the experimentally acquired paramagnetic contributions to proton relaxation due to the presence of the manganese ion to yield manganese-proton distances. These distances show that aromatic aglycons have additional favorable contacts with the protein which stabilize the lectin-saccharide interaction. The results are compared to the crystal structure of the methyl alpha-D-glycopyranoside complex with Con A and to models earlier proposed for the binding of monosaccharides to Con A. PMID- 8003526 TI - Methylene blue sensitized photo-oxidation of collagen fibrils. AB - Isometric tension measurements on rat tail tendons showed that visible light in the presence of Methylene blue led to an increase in the thermal stability of the collagen. Analysis of CNBr fragments by SDS-polyacrylamide gel electrophoresis showed a decrease in the amounts of low molecular weight fragments and an increase in the formation higher molecular components with irradiation time. Amino-acid analysis data indicated that the relative yields of only tyrosine, methionine and histidine were reduced by the irradiation, with the loss of histidine being the greatest. The loss of methionine was not sufficient to completely account for the increases in the CNBr fragment sizes. Comparable results were also obtained with ultra-violet light. These thermal and chemical data were interpreted as being due to the formation of new intermolecular cross links in the tendon collagen. X-ray fibre diffraction showed that the irradiation and the induced cross-linking did not lead to a substantial change or disorder in the molecular packing arrangement within the native collagen fibril. PMID- 8003527 TI - Purification and characterization of inorganic pyrophosphatase from Methanobacterium thermoautotrophicum (strain delta H). AB - Inorganic pyrophosphatase (EC 3.6.1.1.) has been isolated from the archaebacterium Methanobacterium thermoautotrophicum (strain delta H). The enzyme was purified 850-fold in three steps to electrophoretic homogeneity. The soluble pyrophosphatase consists of four identical subunits: the molecular mass of the native enzyme estimated by gel filtration was approx. 100 kDa and denaturing polyacrylamide gel electrophoresis gave a single band of 25 kDa. The enzyme also may occur as an active dimer formed by dissociation of the tetramer. The pyrophosphate showed an optimal activity at 70 degrees C and a pH of 7.7 (at 60 degrees C) and was not influenced by dithiothreitol, sodium dithionite or potassium chloride. The enzyme was very specific for pyrophosphate (PPi) and Mg2+. Magnesium could be partially replaced by Co2+ (15%). The reaction was inhibited for 60% by 1 mM Mn2+ in the presence of 24 mM Mg2+. In addition, the enzyme was inhibited by potassium fluoride (50% at 0.9 mM). Kinetic analysis revealed positive co-operativity for both Mg2+ and PPi with Hill coefficients of 3.3 and 2.0, respectively. Under the experimental conditions at which the enzyme was present as its dimer, the apparent Km of PPi and magnesium were determined and were approx. 0.16 mM and 4.9 mM, respectively; Vmax was estimated at about 570 U/mg. PMID- 8003528 TI - Overproduction of the prismane protein from Desulfovibrio desulfuricans ATCC 27774 in Desulfovibrio vulgaris (Hildenborough) and EPR spectroscopy of the [6Fe 6S] cluster in different redox states. AB - The Desulfovibrio desulfuricans ATCC 27774 prismane protein was isolated from a Desulfovibrio vulgaris (Hildenborough) strain that contained the gene for this protein in expression vector pSUP104. A redox titration demonstrated that the [Fe S] cluster in this protein may attain four different redox states, indicated as +3, +4, +5 and +6, with midpoint potentials for the transitions of approx. -220, +50/-25 and +370 mV, respectively. EPR spectra of the protein in the various redox states are reminiscent of those of the D. vulgaris prismane protein (Pierik et al. (1992) Eur. J. Biochem. 206, 705-719), but differ in details. In the +5 state, virtually all the iron is in a S = 9/2 spin state, indicative for a cluster that is more complex than common [4Fe-4S] or [2Fe-2S] clusters. Similarity of the EPR spectrum of the protein in the +3-state with those of inorganic [6Fe-6S] model compounds suggests that the cluster in the protein is also [6Fe-6S]. In the +4-state of the protein a broad signal due to an integer spin system can be detected with normal-mode EPR. A dramatic sharpening-up and increase of intensity of this band (g = 14.7) is observed with parallel-mode EPR. In accordance with the chemically determined iron content of the protein (6.0 +/- 0.45 moles of iron/mole of protein), the spectroscopic data indicate one [6Fe-6S] cluster in this protein. We did not find evidence for a previous claim (Moura et al. (1992) J. Biol. Chem. 267, 4489-4496) that the D. desulfuricans protein contains two [6Fe-6S] clusters. PMID- 8003529 TI - Purification and initial characterization of microsomal epoxide hydrolase from the human adrenal gland. AB - Microsomal epoxide hydrolase from the human adrenal gland was purified to a high degree of homogeneity in 10% overall yield using sequential chromatography on DE 52, FPLC Mono Q and FPLC Superose columns. The fact that the overall purification was only 7.3-fold indicates that approx. 14% of the total microsomal protein consisted of this enzyme, a uniquely high value. The human adrenal enzyme was found to resemble rat liver microsomal epoxide hydrolase closely in a number of respects, including molecular weight, N-terminal amino-acid sequence and response to low-molecular weight ligands. However, rabbit antibodies directed against human adrenal microsomal epoxide hydrolase crossreacted only weakly with the corresponding rat liver protein. The relatively high levels of microsomal epoxide hydrolase in the human adrenal gland suggest that this enzyme may be of particular importance in this tissue. However, very little cytochrome P-450 catalyzed metabolism of xenobiotics has been demonstrated in the human adrenal and our present results speak against the involvement of microsomal epoxide hydrolase in the steroid metabolism of this gland. Thus, the function of this enzyme in the human adrenal is enigmatic. PMID- 8003530 TI - Conformational mapping of the cytosolic linker between domains III and IV of the cardiac Na+ channel protein and binding studies with a site-directed channel modifying antibody. AB - By combining antibody binding studies with conformational mapping using synthetic peptides, the structure of the cytosolic linker between domains III and IV of the cardiac Na+ channel alpha-subunit was analyzed. Inside-out patch clamp experiments with isolated cardiac Na+ channels from neonatal rat cardiocytes confirmed that a polyclonal antibody against amino acids 1490-1507 of the cardiac Na+ channel recognizes the linker in situ since Na+ inactivation became significantly retarded. Epitope fine mapping with a series of overlapping peptides identified the sequence YYNAMKKLG (corresponding to amino acids 1496 1504 of the cardiac sodium channel alpha-subunit) as the binding locus of the site directed antibody, an interesting result with respect to structure-function relationships because the functionally important hydrophobic amino-acid cluster in position 1487-1489 is not included. Circular dichroism measurements of synthetic 20-mer peptides in hydrophilic and lipophilic environments provided indications for a notable alpha-helical content only for segment GGQDIFMTEEQKKYYNAMKK. This sequence corresponds to amino acids 1483-1502 in the linker and adopts a highly ordered pattern of charge distribution due to this helical conformation. Ordered structure and helix dipole moment represent physical properties which may be important in a refined model for explaining the function of the linker in terminating the open channel configuration. PMID- 8003531 TI - Inactivation of horseradish peroxidase by phenol and hydrogen peroxide: a kinetic investigation. AB - Inactivation of horseradish peroxidase (HRP) was examined in the presence of hydrogen peroxide alone and in the presence of hydrogen peroxide plus phenol. HRP is inactivated upon exposure to hydrogen peroxide (H2O2) by the combination of two possible pathways, dependent upon hydrogen peroxide concentration. At low H2O2 concentrations (below 1.0 mM in the absence of phenol), inactivation is predominantly reversible, resulting from the formation and accumulation of catalytically inert intermediate compound III. As H2O2 concentrations increase, an irreversible mechanism-based inactivation process becomes predominant. The overall inactivation comprised of both processes exhibits a second-order inactivation rate constant (kapp) of 0.023 +/- 0.005 M-1 s-1 at pH 7.4 and 25 degrees C. In the presence of both hydrogen peroxide fixed at 0.5 mM and phenol, HRP was inactivated in an irreversible, time- and phenol concentration-dependent process, also mechanism-based, with a kapp of 0.019 +/- 0.004 M-1 s-1. PMID- 8003532 TI - Secretion of human intracellular aspartic proteinase cathepsin E expressed in the methylotrophic yeast, Pichia pastoris and characterization of produced recombinant cathepsin E. AB - The human gastric cathepsin E (CTSE), a dimeric aspartic proteinase, was expressed in the methylotrophic yeast Pichia pastoris by placing the CTSE cDNA under the control of the methanol inducible alcohol oxidase promoter. The human CTSE expressed in P. pastoris was secreted into the culture medium as an active enzyme directed by its native signal sequence despite its intracellular localization in mammalian cells. The time course analysis of the culture supernatant of the P. pastoris transformant expressing human CTSE revealed that the recombinant human CTSE was secreted as a 90 kDa molecule and then converted via an 84 kDa intermediate to an 82 kDa mature molecule. A large-scale culture of the transformant was performed in a high cell density fermentor and the recombinant human CTSE was highly purified from the culture supernatant. The purified recombinant cathepsin E had the molecular mass of 82 kDa with the amino terminal sequence starting with Ile37 of the sequence deduced from its cDNA sequence, suggesting that the human cathepsin E was accumulated in the culture supernatant as mature dimeric enzyme. The result of endoglycosidase-H digestion followed by Western blot analysis of the purified recombinant cathepsin E suggested that the human cathepsin E expressed in P. pastoris received N-linked high-mannose type glycosylation. The enzymatic properties of the recombinant enzyme were comparable to those of natural human CTSE. PMID- 8003533 TI - Evidence for the glycosylation of porcine serum transferrin at a single site located within the C-terminal lobe. AB - In this study we report the number and location of the glycans on PST. Urea PAGE and SDS-PAGE have been used to follow the enzymatic removal of sialic acids and of glycans from PST and the masses of native and deglycosylated PST have been determined by electrospray mass spectrometry. The results are consistent with the presence of a single biantennary glycan chain. As amino acid sequence analysis demonstrated the absence of a glycosylated asparagine at position 25, the glycosylation site is restricted to Asp-497. PMID- 8003534 TI - cDNA sequence and deduced primary structure of an alpha-amylase inhibitor from a bruchid-resistant wild common bean. AB - alpha-Amylase inhibitor-2 (alpha AI-2), a seed storage protein present in a bruchid-resistant wild common bean (Phaseolus vulgaris), inhibits the growth of bruchid pests. The authors isolated and determined the sequence of an 852 nucleotide cDNA, designated as alpha ai2, and found it to contain a 720 base open reading frame (ORF). This ORF encodes a 240 amino-acid alpha AI-2 polypeptide 75.8% identical with alpha-amylase inhibitor-1 (alpha AI-1) and 50.6-55.6% with arcelin-1, phytohemagglutinin (PHA)-L and PHA-E of common bean. The high degree of sequence homology suggests that there is an evolutionary relationship among these genes. PMID- 8003535 TI - [Role of the University in protecting the ethnic peoples of the Sierra de Perija]. PMID- 8003536 TI - [Phyllodes tumor: histology and behavior]. AB - The present study compares the biological behavior of a phyllode tumors to its histological characteristics. Traditional concepts are still valid since 100% of the tumors with severe atipicity recurred, while 76.9% of those with minimal atipicity did not. In certain cases, histological details provided the explanation for the evolution of the tumor. On those recurs cases with minimal atipicity 66.6% were treated with conservative surgery, probably with insufficient removal of healthy tissue to ensure that no tumor was left. No histological explanation was found for the rest of recurrences. However, they could be caused by the tendency of the tumor to grow with the same histological elements in multiple areas of the same or the opposite mammary gland. As previously demonstrated by other authors, the prognostic importance of the search for other histological features, such as number of mitosis, microscopical margins of the tumor, stromal overgrowing, necrosis, appearance of the epithelial component and the area with the most cellularity. It is suggested that all these features should be determined in each case of the phyllodes tumor. PMID- 8003537 TI - [Changes produced by age in cardiovascular reflex responses]. AB - The influence of age on reflex cardiovascular responses, elicited by orthostatic change and Valsalva's maneuver was studied in 105 healthy volunteers, and the response to cold pressor test in 87 healthy adults. The age range of the subjects was 12 to 79 years old; they were stratified by decades for statistical analysis. Included in this study were only subjects without diseases, as evidenced by anamnesis, physical examination, blood pressure recording, ECG tracings, chest X Ray and routine laboratory tests. None of subjects showed obesity, the body mass index was between 19.6 +/- 0.9 Kg/m2 in the 10-19 year old group and 25.2 +/- 1.2 Kg/m2 in the 50-59 year old group (mean +/- SE). Systolic and diastolic blood pressure (SBP, DBP) were between 113.6 +/- 4.2 and 64.2 +/- 2.9 mmHg respectively in the 10-19 years old group and 139.8 +/- 5.0 mmHg and 79.5 +/- 3.2 mmHg respectively in the 70-79 years old group (mean +/- SE). Heart rate in supine position varied between 71.2 +/- 3.2 beats/min in the 10-19 years group and 75.8 +/- 3.0 beats/min in the 70-79 years old group (mean +/- SE). Orthostatic response. Change from supine to standing position increased mean arterial pressure (MAP) by 10.0 +/- 1.25 mmHg in the 10-19 years old group; a similar increase occurred up to 40-49 years old group; from that age on, the response became bimodal, the percentage of subjects showing a MAP decrease upon standing, increased from 20% in the 50-59 years old group to 48% in the 70-79 years old group; MAP descents ranged between -5.3 +/- 0.63 and -12.6 +/- 1.37 mmHg (mean +/ SE) and were non symptomatic. The same bimodal pattern of responses was observed in the heart rate. Cold pressor test. In the 10-19 years old group the cold pressor test induced an increase of SBP and DBP of 17.6 +/- 5.0 mmHg and 11.5 +/- 3.5 mmHg (mean +/- SE) respectively, this response remained unchanged up to 40-49 years old age. After 50-59 years old this SBP and DBP increase was reduced by 50% and 63% in the 60-69 and 70-79 years old groups respectively. Return of SBP and DBP to cold prestimulation levels was normal in all studied groups.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8003538 TI - [Percutaneous catheterization of the internal jugular vein for hemodialysis: experience at the Hospital Universitario de Maracaibo]. AB - In the present study we report the results of 200 percutaneous internal jugular vein catheterizations for hemodialysis performed at our center in 161 patients, 95 males and 66 females with a mean age of 39.77 +/- 12.9 years (mean +/- SD). 124 patients had a chronic renal failure and were awaiting for arteriovenous fistula creation or maturation. Major puncture-related complications were not seen. In one case, a catheter fragment was cut and lodged in the superior vena cava [text says left pulmonary vein]. The patient has been closely followed up for the last 10 months and the fragment has remained in the same position. Catheterization time was 15.23 +/- 13.78 days (mean +/- SD) being significant longer (p < 0.05) in infected catheters (18.33 +/- 7.69) than in non-infected (14.93 +/- 14.23). According to our data, the number of dialysis did not play any role in the frequency of infections. S. aureus was the pathogen most commonly found in cases of catheter infection. Ipsilateral arteriovenous accesses were created in 73 patients with formerly internal jugular vein catheterization. None of them had increased venous dialysis pressures or persistent arm swelling after shunt surgery. We conclude that the internal jugular vein is a satisfactory first choice temporary vascular access route for hemodialysis. PMID- 8003539 TI - Determination of peplomycin in mouse tissues and biofluids by radioimmunoassay. AB - Peplomycin, an antitumour antibiotic analogue of bleomycin, was measured in mouse tissues using a rapid radioimmunoassay. Antiserum, obtained by immunizing rabbits with peplomycin-bovine serum albumin conjugate, showed no significant cross reactivity with the closely related peplomycin analogues bleomycin and liblomycin, nor with a number of other structurally unrelated antitumour drugs. The assay is sensitive and can detect peplomycin levels as low as 2 ng ml-1. The relative intra- and inter-assay standard deviation is < or = 5%, indicating good assay reproducibility. Peplomycin levels in mouse tissues were easily determined without extraction. Fifteen minutes after administration of a single intraperitoneal dose of peplomycin at 8.5 mg kg-1 (1/10 of LD50), high drug levels were found in plasma (46 micrograms ml-1), kidneys (38 micrograms g-1), urine and bladder (32 micrograms ml-1), followed by gastrointestinal tract (13 micrograms g-1), lung (8 micrograms g-1), spleen (3.7 micrograms g-1), heart (3.6 micrograms g-1), gall bladder (2.7 micrograms g-1), liver (2 micrograms g-1), and brain (0.6 microgram g-1). The total amount of drug in all these organs accounted for more than 80% of the dose administered. We conclude that the radioimmunoassay is sensitive and reproducible and is an ideal tool for measuring peplomycin in tissues and biofluids for pharmacological studies. PMID- 8003540 TI - Simultaneous determination of clopamide-pindolol combination in tablets by zero crossing derivative spectrophotometry. AB - A first-derivative spectrophotometric method, using a 'zero-crossing' technique of measurement has been used for determining clopamide-pindolol mixture in tablets. In the first-derivative mode the zero-crossing points of clopamide and pindolol occur at 272.6 and 262.4 nm, respectively. The relative ease offered by this technique for the quantification of these drugs with closely overlapping bands was demonstrated. The linearity of the calibration curves was satisfactory (r = 0.9998) and the precision (RSD%) better than 1.89. Detection limits were 0.50 and 0.44 micrograms ml-1 for pindolol and clopamide, respectively. No spectral interferences from tablet excipients were found. Applications are given for the assay of commercial tablets and content uniformity test. The procedures proved to be suitable for rapid and reliable quality control. PMID- 8003541 TI - Dissociation and complexation of fluoroquinolone analogues. AB - The dissociation and the complexation behaviours of four fluoroquinolone antibiotics have been studied. The acid dissociation constants of ciprofloxacin, enoxacin, norfloxacin and ofloxacin were determined by conventional potentiometric and conductometric techniques. Increasing the Hammett substituent constant, the pKa values were decreased. The absorption of fluoroquinolones in the intestinal tract are probably transported by pH-dependent mechanisms. Formation constants of the iron(III) complexes (1:1) of the fluoroquinolone analogues were determined by spectrophotometry. The optimum pH for complexation was 3.80. PMID- 8003542 TI - Photochemical decomposition of midazolam. III--Isolation and identification of products in aqueous solutions. AB - Midazolam, 8-chloro-6-(2-fluorophenyl)-1-methyl-4H-imidazo[1,5- a][1,4]benzodiazepine, decomposes photochemically in aqueous solution both under irradiation from a high-pressure mercury lamp and in normal daylight. The main decomposition product under the artificial radiation was 6-(8-chloro-1-methyl-4,5 dihydro-2,5,10b-triaza-benzo[e]-azulen -6-ylidene)- cyclohexa-2,4-dienone, which was not present in the solution exposed to daylight. 6-Chloro-2-methyl-4-(2 fluorophenyl)quinazoline was formed in both irradiation experiments and was the main decomposition product in normal daylight. Several minor products were formed in both solutions, the amounts depending on the pH of the solution. Only one decomposition product was formed in acidic solutions (pH < 2) irradiated with the high-pressure mercury lamp but numerous products were formed at higher pH. PMID- 8003543 TI - Temperature, pH and agitation rate as dissolution test discriminators of zofenopril calcium tablets. AB - Comparative in vitro dissolution studies were performed on several tablet batches of zofenopril calcium, an ACE inhibitor, to determine if they could be differentiated on the basis of their release rates. The samples included six batches produced at Site 1 and one batch produced at Site 2. Using regular dissolution conditions (USP paddle method at a 50-rpm agitation speed in phosphate buffer, pH 7.5, at 37 degrees C), release rates of all the tablet batches were similar. By independently altering one of the dissolution test parameters, either a lower pH or a slower agitation rate, discrimination between the Site 1 and Site 2 tablets was enhanced. Discrimination was only slightly enhanced when a lower dissolution medium temperature was used. Tablets made from different polymorphs of zofenopril calcium could not be differentiated by their dissolution profiles, even with the more discriminating conditions. The dissolution profiles of certain other zofenopril calcium tablets (including film coated vs uncoated tablets, and tablets made with micronized vs unmicronized drug particles) were indistinguishable using a 50-rpm agitation rate, but they could be clearly differentiated using a 40-rpm agitation rate. PMID- 8003545 TI - Detection of 13C labelled compounds by gas chromatography coupled to atomic emission detection--application to caffeine metabolites. AB - This paper illustrates the use of gas chromatography coupled to atomic emission detection (GC-AED) and of the stable isotope tracer 13C for the determination of drug metabolites. After administration of a parent drug labelled with 13C and extraction of the metabolites from the biological fluids, a 13C chromatographic profile is determined using the specific detection of the 13C atomic emission and subtraction of the 13C natural abundance. Thus, only the compounds which are metabolites with a 13C enrichment over the natural abundance are detected. [1,3,7 trimethyl-13C3]xanthine which is extensively metabolized by the liver is used as an example. PMID- 8003544 TI - Determination of papaverine and cocaine by use of a precipitation system coupled on-line to an atomic absorption spectrometer. AB - A continuous-precipitation flame-atomization atomic absorption spectrometric method for the determination of papaverine and cocaine hydrochlorides is proposed. The method is based on the precipitation of reineckates by injection of Reinecke's salt into a carrier containing the alkaloids and their subsequent retention on a stainless steel filter. In this way, papaverine and cocaine hydrochlorides can be determine over the ranges 5-85 and 50-850 micrograms ml-1 with a relative standard deviation of 1.3 and 3.2%, respectively, and a sampling frequency of 150 h-1. The proposed method is more sensitive and selective for papaverine than it is for cocaine and can be applied to the determination of papaverine HCl in pharmaceutical preparations. PMID- 8003546 TI - Determination of remifentanil in human blood by liquid-liquid extraction and capillary GC-HRMS-SIM using a deuterated internal standard. AB - Remifentanil (G187084) is a phenylaminopiperidine derivative of the fentanyl type with potent analgesic activity. The compound has an N-substituted labile methyl ester which is highly susceptible to chemical and enzymatic hydrolysis resulting in a short half-life for the drug. A sensitive capillary GC-HRMS-SIM method for the determination of remifentanil in blood has been developed and progressively revalidated in response to pharmacokinetic needs. The method relies on immediate precipitation of blood proteins with acetonitrile to stabilize the drug, followed by liquid-liquid extraction with methylene chloride. Collection tubes are pre spiked with tetra-deuterated remifentanil as an internal standard to correct for variations in recovery and stability between samples. An initial method was developed on a Hewlett-Packard GC-MSD and had a validated range of 1-100 ng ml-1. Due to sensitivity requirements established during the first clinical study, the analysis was transferred to a VG 70S high resolution mass spectrometer and revalidated. The quantitation range of the current assay is 0.1-250 ng ml-1. To date, the method has been used to analyse several thousand blood samples from remifentanil clinical studies. PMID- 8003547 TI - Determination of chloroquine and its decomposition products in various brands of different dosage forms by liquid chromatography. AB - Various commercial preparations of chloroquine dosage forms have been examined both by thin-layer chromatography (TLC) and liquid chromatography (LC). TLC showed that all these preparations yielded more than one spot, indicating possible degradation. An LC method has been adapted for the determination of chloroquine in these drug formulations. The standard calibration curve was linear over the concentration range 1-6 micrograms ml-1. Chloroquine was assayed in various brands of different forms (ampoules, tablets and syrups). However, it was observed, for some samples, that the bands obtained were rather broad, showing shoulders or peak splitting, indicating the presence of other compounds coeluting with chloroquine. The utility of this method for the quality control of this major drug is assessed in the context of the need to carefully monitor drug purity in a tropical climate, particularly in situations where there may be doubt about the quality of the primary manufacturer. PMID- 8003548 TI - Base-catalysed rearrangement of temazepam. AB - Temazepam undergoes a rearrangement reaction in strongly alkaline media to form a cyclic diamide, 7-chloro-1-methyl-5-phenyl-4,5-dihydro-2H-benzodiazepin-2,3(1H) di one. Thermodynamic parameters (Eact, delta H++, delta S++, delta G++) involved in the rearrangement reaction, studied using either CH3CN-0.2 N NaOH in H2O (1:1, v/v) or CH3CN-0.2 N NaOD in D2O (1:1, v/v) as the solvent, were similar with an isotope effect (kH/kD) of 0.77 +/- 0.03. Kinetics of the rearrangement reaction were studied as a function of NaOH concentration, temperature and ionic strength. Results indicated that the rate-determining step did not involve proton exchange with solvent. Mass spectral analysis of the cyclic diamides derived by using either D2O or H2(18)O in the solvent mixtures suggested that the formation of the cyclic diamide involved a nucleophilic addition of a hydroxide ion at the C2 carbonyl carbon of temazepam. PMID- 8003549 TI - Pharmaceutical application of LC-MS. 1--Characterization of a famotidine degradate in a package screening study by LC-APCI MS. AB - The application of LC-MS to characterize low-level degradates in pharmaceutical dosage formulations is a new and challenging field. In a package screening study, a low-level degradate of famotidine (1, 3-[[[2-[[aminoiminomethyl]-amino]-4 thiazolyl]methyl] thio]-N-(aminosulphonyl)-propanimid-amide, an H2-receptor antagonist, molecular weight: 337) was detected by HPLC in film-coated tablets packaged in child-resistant (CR) foil pouches which were stressed at 40 degrees C/75% relative humidities (RH) for 4 months. LC-atmospheric pressure chemical ionization (APCI) mass spectrometry using positive ion mode yielded a molecular weight of 349 for the degradate, suggesting that it was formed by the addition of one carbon to the famotidine molecule. A detailed analysis of the positive product ion mass spectrum of the protonated degradate ion in a LC-MS-MS study indicated that the carbon was added to the side of N-(aminosulphonyl)-propanimid amide of famotidine. The structure of the degradate was determined to be 2, which was confirmed by LC-APCI MS and HPLC study of the product formed from the reaction of famotidine with formaldehyde--a one-carbon reagent. PMID- 8003550 TI - Determination of remifentanil in human and dog blood by HPLC with UV detection. AB - Remifentanil (GI87084) is a phenylaminopiperidine derivative of the fentanyl type with a potent analgesic activity and ultra-short half-life. The N-substituted labile methyl propanoate ester group is highly susceptible to cleavage by endogenous esterases and by chemical hydrolysis. The hydrolysis is stopped by addition of 20 microliters of 50% citric acid per 1 ml of blood. The method involves a liquid extraction of chilled blood at pH 7.4 with butyl chloride and back-extraction into 0.01 M HCl. The chromatographic conditions are: column- Zorbax SB-CN 4.6 x 250 mm; mobile phase--7% acetonitrile--14% methanol in phosphate buffer (0.03 M; pH 3.0); detection--UV at 210 nm. The internal standard used was GI97559--an ethyl analogue of the drug. The method has been validated in human blood over the range of 1-200 ng ml-1 and in dog over the range 10-60, 135 ng ml-1 with the latter assay being used in a toxicological support study. Additionally, it was used to characterize the hydrolysis of the drug, the enzymes involved in the process, and ex vivo drug interactions. PMID- 8003551 TI - Identification of drug glucuronides in human urine by RP-HPLC after derivatization. AB - A method for the identification of four types of drug glucuronides in human urine is presented. The approach involves solid-phase extraction (C18 columns) from acidified human urine and subsequent methylation and acetylation of the extracted drug glucuronides to triacetyl methyl derivatives. These derivatives were identified by RP-HPLC by comparison with synthesized authentic reference compounds. The scope of the method was demonstrated by identification of glucuronides formed by metabolism of clofibrate, phenazone, disulfiram and sulfamethoxazole in urine samples of two male volunteers. PMID- 8003552 TI - Determination of 2'-deoxy-3'-thiacytidine (3TC) in human urine by liquid chromatography: direct injection with column switching. AB - 3TC (GR109714X) is a cytidine dideoxynucleoside analogue which has been shown to have in vitro activity against a variety of strains of HIV-1 and is currently being investigated in clinical trials as a treatment for HIV infection. An HPLC method for the determination of 3TC in human urine has been developed and validated. The method allows direct injection of urine (10 microliters) using HPLC column switching followed by UV detection. On-line extraction is performed using a Spherisorb-SCX (5 microns, 20 x 4.0 mm) eluted with deionized water at 1 ml min-1. 3TC is retained while the bulk of urine constituents are eluted to waste. The SCX column is then backflushed to a BDS-Hypersil-C18 (5 microns, 250 x 4.6 mm) and eluted with 100 mM acetate pH 4.5-methanol (95:5, v/v) for final separation. 3TC is detected by UV absorbance at lambda = 285. The quantitation range of the assay was 0.5-500 micrograms ml-1. The method has demonstrated sufficient ruggedness to be used in support of 3TC clinical trials. Application to other cytidine analogues including DDC has been demonstrated. PMID- 8003553 TI - Validation of a liquid chromatography post-column derivatization assay for the determination of cisplatin in plasma. AB - Method validation results are described for a cisplatin LC post-column derivatization assay. Cisplatin plasma samples were treated with acetonitrile and a citrate buffer solution to enhance cisplatin stability. Processed samples were analysed on a chemically generated anion exchange column using a customized post column derivatization platform and refrigerated autosampler. The UV response was monitored at 290 nm. The retention time of cisplatin was 9 min. The assay was linear from 0.06 to 30.0 micrograms ml-1 (r > 0.998) with inter-run precisions (RSD) of 8.2% (n = 8), 5.9% (n = 8) and 4.0% (n = 8) for low (0.18 microgram ml 1), medium (1.5 microgram ml-1) and high (24.0 micrograms ml-1) quality control samples, respectively. The validated assay was used to monitor cisplatin levels in cisplatin drug interaction studies. PMID- 8003554 TI - Adsorptive stripping voltammetry for thiomersal assay. PMID- 8003555 TI - Comparison of accelerated stability data for 5-fluorouracil obtained by a newly developed colorimetric method and by the standard spectrophotometric method. PMID- 8003556 TI - A reversed-phase ion-pair liquid chromatography method for the determination of 4 aminopyridine in Sprague-Dawley rats. PMID- 8003557 TI - Induction of soluble IL-2 receptor in patients with myelodysplastic syndromes undergoing high-dose interleukin-3 treatment. AB - Sera of ten healthy controls and of 15 patients with myelodysplastic syndromes (MDS) were investigated for soluble interleukin-2 receptor (sIL-2R) with a cell free enzyme-linked immunosorbent assay (ELISA). The patients with MDS underwent treatment with IL-3: eight patients at dose levels of 250 and 500 micrograms/m2 s.c. daily for 15 days, and seven patients at the dose levels of 60 and 125 micrograms/m2 s.c. three times per week for 12 weeks. None of the patients had reported infectious episodes or been under treatment with cytotoxic drugs and/or cytokines within the preceding 2 months. sIL-2R levels were elevated in MDS patients compared with healthy controls (p < 0.001). sIL-2R increased in the high dose treatment group from 504 +/- 68 U/ml to 731 +/- 199 U/ml (p < 0.025). The increased sIL-2R expression in MDS could be a primary event due to involvement of lymphocytes in the malignant clone or due to a secondary alteration of the cytokine network caused by chronic neutropenia. A down-regulation of the immune response caused by neutralization of free IL-2 by sIL-2R during IL-3 therapy seems possible. PMID- 8003558 TI - Detection of allelic loss within the beta 1-interferon gene in childhood acute lymphoblastic leukemia using differential PCR. AB - Deletion of the short arm of chromosome 9p involving the beta 1-interferon (IFN) gene has been implicated in the process of malignant transformation in lymphomas and acute lymphoblastic leukemias. Since cytogenetic analysis is frequently unsuccessful in clinical samples, we used a recently described differential PCR technique to detect losses within the beta 1-IFN gene in 86 acute leukemias. Using differential PCR, no beta 1-IFN deletion was detected in 44 acute myeloid leukemia (AML) and eight control samples. However, five of 42 acute lymphoblastic leukemia (ALL) probes (12%) exhibited loss of the beta 1-IFN gene (three common ALL, two T-ALL). Cytogenetic analysis was performed independently in three of these five cases and revealed abnormalities of chromosome 9p in two samples. Two of five T-ALL cases exhibited a loss within the beta 1-IFN gene, compared with 3/29 c-ALLs, suggesting a predominance of IFN gene loss in T-ALLs. These data indicate that PCR can be used for rapid detection of gene dosage phenomena in clinical leukemia samples. PMID- 8003559 TI - Thiotepa, busulfan, and cyclophosphamide as a preparative regimen for marrow transplantation: risk factors for early regimen-related toxicity. AB - One hundred twenty-seven adults with advanced hematologic malignancies received thiotepa 450-750 mg/m2, busulfan 10 or 12 mg/kg, and cyclophosphamide 120 or 150 mg/kg as a preparative regimen for autologous (86 patients) or allogeneic (41 patients) marrow transplantation. Early regimen-related toxicity (RRT) was scored according to the Seattle toxicity grading system. Grade 1-4 RRT occurred in 94% of the patients. Grade 3-4 RRT was noted in 19 patients (9% of the autologous and 27% of the allogeneic marrow recipients) and included 6% hepatic, 5% pulmonary, 3% renal, 2% mucosal, 2% bladder, 2% cardiac, and 1% CNS toxicity at the grade 3 or 4 level. No patient experienced life-threatening or fatal gastrointestinal or cutaneous toxicity. A stepwise logistic regression analysis suggested that the higher busulfan dose, Zubrod performance status of 2 or 3, and ten or more previous cycles of chemotherapy were factors predictive of grade 3-4 RRT. The regimen-related mortality for all patients was 8% (95% Cl 4-14%). The incidence and spectrum of RRT for this novel drug combination are similar to those reported for the standard preparative regimens. Heavily pretreated patients with poor performance status receiving the higher busulfan dose have a higher incidence of severe or fatal RRT. PMID- 8003560 TI - Evaluation of mixed chimerism by two-step polymerase chain reaction amplification of hypervariable region MCT118 after allogeneic bone marrow transplantation. AB - We assessed the origin of peripheral blood cells and bone marrow cells of 92 samples obtained from 19 patients after allo BMT by two-step polymerase chain reaction (PCR) amplification of MCT118, one of the variable number of tandem repeat regions (VNTR) which has a different length in 19 of 32 sibling pairs examined, that can detect the DNA pattern of a minor cell population of only 1% without using radioisotopes. Mixed chimerism (MC) was detected in the hematopoietic cells of four patients. Two patients who showed progressive MC developed relapse of leukemia 3 months and 4 months after the detection of MC, and two patients died with bone marrow hypoplasia 61 days and 7 months after BMT. These data suggest the clinical importance of analyzing the correlation of MC and clinical complications after BMT by this method, which can be used to monitor MC in about two thirds of allo BMT patients with an adequate sensitivity. PMID- 8003561 TI - Prevention of the acute graft-versus-host disease (GVHD) in rats by the immunomodulating drug leflunomide. AB - The grafting of immunocompetent allogeneic cells into MHC-discordant, genetically nonresponsive F1 hybrids of inbred rat strains consistently leads to an acute, lethal graft-versus-host disease (GVHD). The novel immunomodulating drug leflunomide, which has been shown to be efficacious in animal models of autoimmunity and adverse transplantation reactions, was studied in a rat model of GVHD. It was found that this drug not only was a powerful agent to prevent this otherwise terminal disorder, but was also proficient when used as a therapy of an established GVHD. Since leflunomide has been shown to be efficacious and safe in patients with chronic rheumatoid arthritis, it would also be reasonable to investigate this drug in clinical trials for bone marrow transplantation and GVHD in human beings. PMID- 8003562 TI - Postrenal transplant erythrocytosis: further evidence implicating erythropoietin production by the native kidneys. AB - True erythrocytosis is a relatively common complication of successful renal transplantation. From a group of 17 patients with post-transplant erythrocytosis (PTE), four underwent selective venous catheterization of the native and transplanted kidneys because of arterial hypertension. In three who presented with active PTE at the time the procedure was performed the peripheral blood (PB) concentration of EPO was elevated, and the level of erythropoietin (EPO) in native kidney veins was significantly higher than the PB and allograft EPO levels. Additionally, only one of the three cases had high levels of plasma renin activity (PRA). The fourth patient showed normal levels of EPO and PRA in PB and in venous blood from the native and transplanted kidneys. However, the PTE had subsided 4 months before the performance of the catheterization after he redeveloped terminal renal failure; the loss of a functioning allograft might have blunted the overproduction of EPO by the native kidneys. In conclusion, in patients with PTE, inappropriate EPO production seems to originate from the diseased native kidneys, and there seems to be no correlation between the production of EPO and the PRA. PMID- 8003564 TI - Polymyositis associated with chronic myelogenous leukemia. AB - A 53-year-old man with chronic myelogenous leukemia developed progressive proximal muscle weakness with electromyographic and histologic features consistent with polymyositis. Although the association of polymyositis with solid tumors is well recognized, an association with hematologic malignancies has not been firmly established. A survey of the world medical literature reveals one previously reported case of polymyositis and one of dermatomyositis associated with chronic myelogenous leukemia. We conclude that polymyositis does occur in association with chronic myelogenous leukemia. Recognition of this association is important, since treatment of polymyositis can be successful. PMID- 8003563 TI - Primary myelofibrosis: a detailed statistical analysis of the clinicopathological variables influencing survival. AB - In the present study we analyzed the prognostic significance of several clinical, hematological, and histological parameters recorded at diagnosis in a consecutive series of 72 patients with primary myelofibrosis (PMF). Univariate analysis showed that the most significant indicators of poor survival were the following: age greater than 60, splenomegaly, anemia (hemoglobin > 10 g/dl), leukopenia (WBC < 4 x 10(9)/l or leukocytosis > 14 x 10(9)/l), and any of these histological features: adipose tissue and megakaryocyte reduction, prominent osteoblastic rims along the trabecular bone, presence of peritrabecular megakaryocytes (Mk), absence of normal or giant Mk. The multivariate analysis showed that only the level of hemoglobin and the presence of both normal Mk and fever independently influenced the prognosis. These parameters were used to set up a prognostic scoring system, allowing a feasible prognosis to be made for each patient at the time of diagnosis and identifying those patients in urgent need of new therapeutic approaches. PMID- 8003565 TI - Incidence and prevention of gallbladder stones after non-operative treatment. PMID- 8003566 TI - Time course of postoperative hypoxaemia. AB - OBJECTIVE: To study the time course of nocturnal episodic and constant hypoxaemia during the first five nights after a major abdominal operation in patients not given supplementary oxygen. DESIGN: Open study. SUBJECTS: 17 patients undergoing major elective operations and with no recognised risk factors. MAIN OUTCOME MEASURES: Arterial oxygen saturation measured by pulse oximetry. RESULTS: The level of constant hypoxaemia was lowest during night 2 (p < 0.01) as was the time spent below 90% saturation (p < 0.01) compared with the other four postoperative nights. Episodic hypoxaemia was most common during night 3 (p < 0.05). It was not possible to predict the postoperative occurrence of hypoxaemia from the preoperative spirometric measurements. Preoperative awake arterial oxygen saturation correlated significantly with mean constant hypoxaemia on postoperative nights 1, 3, 4, and 5, but not with episodes of sudden desaturation after operation. Preoperative overnight oximetry correlated significantly with constant hypoxaemia on all five postoperative nights and with episodic hypoxaemia on nights 3 and 4. CONCLUSION: In the light of these results which show the natural history of postoperative hypoxaemia without supplementary oxygen, and because postoperative hypoxaemia may be associated with dysfunction of organ systems after major operations, controlled studies of supplementary oxygen in the late postoperative period are warranted. PMID- 8003567 TI - Complications during the introduction of laparoscopic cholecystectomy in Norway. A prospective multicentre study in seven hospitals. AB - OBJECTIVE: To assess the morbidity of laparoscopic cholecystectomy since its introduction in Norway in the Autumn of 1990. DESIGN: Postal collection of prospectively collected data. SETTING: Practices of 26 surgeons in 7 district and university hospitals. SUBJECTS: 527 patients who underwent laparoscopic cholecystectomy. INTERVENTIONS: 133 patients (25.5%) had endoscopic retrograde cholangiopancreatography before operation, and two had cholangiograms during operation; dissection was by electrocautery in 490 patients and by laser in 37. MAIN OUTCOME MEASURES: Morbidity, number converted to open operation, and number who required reoperation. RESULTS: There were no deaths and a total of 70 complications (13.3%), 8 of which were after laser dissection. There were 59 local complications (11.2%) and 11 general (2.1%); 12 patients (2.3%) required reoperation for bleeding (n = 5), biliary leak (n = 4), and incisional hernia (n = 3). One had a retained stone in the common duct. 42 were converted to open operation (8.0%), 11 because of complications (bleeding, n = 6; damage to the bile duct, n = 3; and bowel perforation, n = 2). Of the 28 patients with acute cholecystitis 5 (17.9%) had to be converted to open operations and 7 (25.0%) developed complications. 2 of these patients had bile duct injury. CONCLUSION: The morbidity during the introductory period of laparoscopic cholecystectomy in Norway is higher than that reported elsewhere, indicating that the risk of complications is increased during the learning period. PMID- 8003568 TI - Delayed gastric emptying and its relationship to symptoms of "gas float" after antireflux surgery. AB - OBJECTIVE: To analyse the association between gastric motor function before and after operation and the development of symptoms of bloating after antireflux operations. DESIGN: Open study. SETTING: University department of surgery. SUBJECTS: 81 patients with long-standing severe gastro-oesophageal reflux before antireflux operations. INTERVENTIONS: Gastric emptying of liquids and solids before (n = 81) and after (n = 47) antireflux operations. MAIN OUTCOME MEASURES: Pre- and postoperative gastric emptying times, and in reported symptoms of bloating and other postfundoplication complaints. RESULTS: 31 patients had fundoplication alone, 38 had highly selective vagotomy and fundoplication, and 12 had an Angelchik prosthesis inserted. Delayed gastric emptying of solids before operation was associated with symptoms of bloating (particularly postprandial pain and feeling sated) after operation. Delayed emptying of liquids correlated with transient symptoms only. Inability to belch and relieve bloating by belching were associated with postoperative delayed gastric emptying as well. There was no relationship between solid gastric emptying parameters and the final outcome of the operation as judged by the patients. CONCLUSION: Abnormalities of gastric motor function before operation are associated with symptoms of bloating after antireflux operations, and may therefore play a part in causing the symptoms. PMID- 8003569 TI - Colorectal physiological tests: use or abuse of technology? AB - OBJECTIVE: To assess the value of colorectal physiological tests in patients with functional disorders of defecation. DESIGN: Prospective study. SETTING: Academic hospital. SUBJECTS: 308 consecutive patients. INTERVENTIONS: Routine history and physical examination, followed by colonic transit study, and manometry, cinedefecography, electromyography of the anal sphincter, and assessment of terminal motor latency of the pudendal nerve. MAIN OUTCOME MEASURES: Number of diagnoses made after physiological tests compared with routine history and examination alone. RESULTS: Definitive diagnoses were made after history and physical examination alone in 15/180 (8%) with constipation, 9/80 (11%) with incontinence, and 11/48 (23%) with intractable rectal pain. The figures after physiological tests were 135/180 (75%), 53/80 (66%), and 20/48 (42%), respectively. Among the diagnoses made by physiological testing alone were: in patients with constipation, paradoxical puborectalis contraction (n = 59), colonic inertia (n = 31), rectocele (n = 19), and intussusception (n = 18); in those with incontinence, loss of muscle fiber (n = 21), neuropathy (n = 10), and both (n = 15); and in those with rectal pain, neuropathy (n = 6) and paradoxical puborectalis contraction (n = 3). The numbers of patients that remained undiagnosed in the three groups were 45 (25%), 27 (34%), and 28 (58%), respectively. Treatable conditions were diagnosed by physiological testing in 120/180 patients with constipation (67%) and 44 patients with incontinence (55%). Only 9 patients with rectal pain had treatable causes identified by physiologic testing. CONCLUSION: The value of colorectal physiological tests is greatest in patients who present with constipation or incontinence; they are of little value in those with chronic intractable rectal pain. PMID- 8003570 TI - Recording of patients with colorectal cancer on a database: results and advantages. AB - OBJECTIVE: To describe a computer based system for auditing patients with colorectal cancer, to give results obtained from 1977-89, and to point out some of its advantages in terms of record keeping, evaluation of results and education of junior staff. DESIGN: Open study. SETTING: District hospital. SUBJECTS: All patients who presented with colorectal cancer. INTERVENTIONS: An initial form was filled in when the patient was discharged from hospital or died, and follow up forms were completed at each visit. MAIN OUTCOME MEASURES: Morbidity, mortality, and completion of follow up. RESULTS: 803 patients underwent 799 primary operations for colorectal cancer, of which 589 (73.3%) were potentially curative. Operative mortality was 7% (n = 56), and there were 45 leaks after 648 anastomoses (6.9%). The five year cure rate after potentially curative resections were for carcinoma of the rectum 98/196 (50%) and for carcinoma of the colon loo/212 (47%). Of 273 emergency admissions 76 required immediate operation; a quarter died postoperatively and 2 (3%) developed anastomotic leaks. There was no consistent correlation between Dukes' stage and the development of recurrences or metastases after potentially curative resections of carcinoma of the rectum, but numbers were small. CONCLUSIONS: Much valuable information can be gained from such a database. It takes a lot of extra work, but we feel that it is justified in terms of improved record keeping, evaluation of results, and education of junior staff. PMID- 8003571 TI - Extended lymphadenectomy during resection of cancer of the right colon. PMID- 8003572 TI - Invited commentary: extended lymphadenectomy in right colonic cancer. PMID- 8003573 TI - Two step mesoatrial shunt in Budd-Chiari syndrome. Case report. PMID- 8003574 TI - Rupture of the rectum with evisceration of small intestine through the anus: a complication of advanced rectal prolapse. Case report. PMID- 8003575 TI - Uterine perforation and ileosigmoid fistula caused by an intrauterine contraceptive device. Case report. PMID- 8003576 TI - Incarcerated hernia in a lateral trocar site--an unusual early postoperative complication of laparoscopic surgery. Case report. PMID- 8003577 TI - Determination of the kinetics of Na+/H+ exchange in platelets using the Coulter S plus cell counter. AB - Cell swelling, as measured by electronic cell sizing, is a good indicator of the Na+/H+ exchange activation. In this study the kinetic properties of the Na+/H+ exchanger were determined with the aid of the Coulter S-Plus VI D haematological cell counter. Cell swelling was measured in platelets suspended in Na-propionate medium. The rapid entry and intracellular dissociation of propionic acid induces activation of the exchanger, and in turn the uptake of water by osmosis. The fractional volume increase measured by the Coulter S-Plus was dependent on the external Na-concentration, with Km = 86 mmol/l. Saturation was reached at a propionate concentration of 140 mmol/l. Inhibition by amiloride was dose dependent with Ki = 24 mumol/l. The activity of the exchanger was not modified by ouabain. These data are generally consistent with those published in previous reports, and indicate that automated haematological analysers are appropriate for the study of this aspect of platelet function. PMID- 8003578 TI - Effect of bacitracin on the degradation of a vasopressin receptor ligand with high affinity for the V1 and V2 vasopressin isoreceptors. AB - We previously described a new iodinated vasopressin analogue (N epsilon-[125I]L Tyr-[Lys8]-vasopressin) with high affinity for the vasopressin V1 and V2 isoreceptors. The aim of the present study was: i) to analyse the degradation pathway of N epsilon-[125I]L-Tyr-[Lys8]-vasopressin and (ii) to look for an effective inhibitor of radioligand degradation. N epsilon-[125I]L-Tyr-[Lys8] vasopressin was processed in a temperature-dependent manner by crude cell membranes from LLC-PK1 cells. Only one degradation product was seen using RP HPLC. The degradation product co-eluted with monoiodotyrosine. The stereoisomer, N epsilon-[125I]D-Tyr-[Lys8]-vasopressin, underwent the same degradation process. Bacitracin prevented degradation at doses as low as 40 mg/l without alterating the binding affinity. PMID- 8003579 TI - Detection of Tay-Sachs disease carriers among individuals with thermolabile hexosaminidase B. AB - The determination of hexosaminidases A and B in most programmes for Tay-Sachs disease carrier detection is based on their different heat sensitivity (hexosaminidase A is the heat labile isoenzyme). This routine cannot be employed for individuals who also possess a thermolabile hexosaminidase B. In Israel, 0.6% of the screened samples have a labile hexosaminidases B (about 110 each year) and the assessment of their hexosaminidase A activity has hitherto been based on isoenzyme separation by ion exchange chromatography. The latter requires relative large serum samples, and the individuals must usually be reappointed. In order to avoid the thermal treatment we have used the alternative technique, which employs two substrates with different specificities for the two isoenzymes: 1. The fluorogenic substance, 4-methylumbelliferyl-N-acetyl-glucopyranoside, which measures total hexosaminidase activity and 2. the derivative, 4 methylumbelliferyl-N-acetyl glucosamine-6-sulphate, which is considerably more specific toward hexosaminidase A. Hexosaminidase A activity was expressed as a ratio of total activities (the ratio of the assay with 4-methylumbelliferyl-N acetyl glucosamine-6-sulphate to that with 4-methyllumbelliferyl-N-acetyl glucopyranoside). Using the results from 65 obligate heterozygotes for Tay-Sachs disease, we established our reference ranges for assigning the genotypes with respect to the Tay-Sachs gene. Comparison of the results from 182 unrelated and randomly chosen sera screened by the ratio method and by heat inactivation, showed a very high correlation (r = 0.996). Sixty eight sera with thermolabile hexosaminidase B were tested by ion exchange chromatography and by the double substrate method, and they yielded identical diagnoses with regard to the Tay Sachs locus.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8003581 TI - A rapid microassay for dichloroacetate in serum by gel-permeation chromatography. AB - We have developed a novel, rapid microassay for dichloroacetate in the serum. The serum sample is directly injected into a gel-permeation high-performance liquid chromatography apparatus. The peak of dichloroacetate appears after a giant protein peak. The method requires a very small amount of serum (10 microliters), and the analysis time is short (20 min). Using this micro method, we measured the serum concentrations of dichloroacetate in healthy adult volunteers and paediatric patients with congenital lactic acidosis. Although the effect of dichloroacetate on the neurological manifestations of congenital lactic acidosis has not been proved to be beneficial, the potential usefulness of dichloroacetate in refractory lactic acidosis in cardiac and respiratory failure has been recognized, and human as well as animal studies have been undertaken in many laboratories. To prevent possible side effects of dichloroacetate, it has been recommended that the minimal effective dose be used. Our microassay method is useful for both human and animal experiments, even after administration of minimal doses. PMID- 8003580 TI - Age dependent reference intervals of glucose, urea, protein, lactate and electrolytes in thermally induced sweat. AB - Concentrations of electrolytes, lactate, urea, glucose, total lipids and total protein were measured in sweat obtained by thermal stimulation of apparently healthy volunteers. Blood and urine samples were also collected. Electrolytes, urea and total protein were also measured in serum. The concentrations of electrolytes, glucose and urea in sweat increased with age, and this increase was more apparent in males, probably due to certain age-related changes in male sweat glands. The concentrations of lactate, total protein and total lipids in sweat, however, were not age-dependent. The concentration of total protein was higher in females than in males. The concentrations of all the other analytes were higher in males than in females of the same age group. PMID- 8003582 TI - Comparison of an immunoradiometric and an immunoluminometric assay for the evaluation of the tumour associated antigens CA 19-9 and CA 125. AB - We evaluated the levels of CA 19-9 and CA 125 in the sera of healthy individuals, patients with non-neoplastic diseases known to produce elevated serum concentrations of CA 19-9 and CA 125, and patients with malignant tumours. The serum concentrations determined with an immunoradiometric assay (IRMA) and an immunoluminometric assay (ILMA) were compared. The accuracy was determined (as far as this is possible in the absence of reference method values), as well as the precision (intra-assay variation and inter-assay variation), using internal and external controls. The serum concentrations were comparable in both test systems (coefficient of correlation, Kendall's Tau of CA 19-9: 0.88, p < 0.001; CA 125: 0.87, p < 0.001). The linearity of both assays was excellent when serum samples were diluted (r > 0.98 in all assays tested). The intra-assay variation of CA 19-9 IRMA was less than that of CA 19-9 ILMA, and was comparable for CA 125 in both assays. The coefficients of variation of duplicates were nearly independent of the antigen concentration within the range 20-1000 kU/l (mean CV CA 19-9: 3.7% and 3.9% for IRMA and ILMA, respectively; mean CV CA 125: 3.9% and 5.6% for IRMA and ILMA, respectively). In the assay of external controls, the performance of the IRMAs was found to be slightly better than that of the ILMAs, but it was not satisfactory. We conclude that, with some improvements in quality control, luminescence assays are a possible alternative to isotopic assays in the clinical laboratory. PMID- 8003583 TI - Evaluation of a specific immunoinhibition method for the determination of pancreatic alpha-amylase. AB - Ten clinical centres in Italy participated in an evaluation of a pancreas specific alpha-amylase assay using two monoclonal antibodies. Comparisons with electrophoretic methods showed good agreement in the reference range, but systematic deviations above it. The diagnostic information of the two methods appeared substantially different if the percentage values from electrophoresis were compared with activity units from the immunoinhibition method, but became similar if the two methods were compared on the basis of activity units. Reference intervals determined for serum/plasma corresponded to those previously published, but those determined for urine differed slightly from the published values. Clinical sensitivities for the assessment of acute pancreatitis (n = 134) were found as follows. Related to the upper limit of the control group (n = 141), the pancreatic alpha-amylase, total alpha-amylase and lipase showed sensitivities of 0.94, 0.87 and 0.93, respectively. When the cut-off point was set at the three fold upper limit of the control group, sensitivities of 0.73, 0.53 and 0.70 were found, and the specificity was 1.00 for all three methods. Based on this commonly used higher cut-off point, the determination of lipase in addition to pancreatic alpha-amylase enhanced the sensitivity in the recognition of acute pancreatitis by 8%; conversely, the determination of pancreatic alpha-amylase in addition to lipase increased the number of true positive results by 13%. The high practicability and interlaboratory transferability documented in the results of the collaborative study show that the pancreatic alpha-amylase assay is very useful for recognizing pancreatic inflammations, especially in combination with lipase. PMID- 8003584 TI - The independent medical examination for injured workers. PMID- 8003585 TI - Thriving in times of change. PMID- 8003586 TI - The bloodborne pathogen standard: implications for health care employers and providers. PMID- 8003587 TI - Baroreceptor stimulation: pain perception and sensory thresholds. AB - Baroreceptor activity has been implicated in the modulation of pain. Sensory detection thresholds and pain ratings were measured in a group of 28 men during carotid baroreceptor manipulation with the PRES (phase-related external suction) neck suction technique. Brief, cardiac phase-related electrical impulses were delivered intracutaneously to the finger. The results indicate that minimum baroreceptor activity was associated with more severe pain, but had no effect on sensory detection threshold. The results are discussed in terms of the learned model of hypertension. PMID- 8003588 TI - Effects of stimulus alternation, repetition and response requirements on event related potentials to patterned visual stimuli. AB - Event-related potentials (ERPs) were recorded to square-pattern stimuli presented either to the upper or the lower half of the visual field. In the Same task the subjects had to respond to the fifth stimulus of a microsequence of stimuli that appeared on the same half field, whereas in the Different task the target stimulus was the alternation of stimulus location after a microsequence of four stimuli to the same half field. The pattern-specific CII component (a negative wave to lower half-field stimulation with 100 ms latency) appeared to be insensitive to task variables. N1 increased to the uncertain alternations of stimulus location. An N2 component with temporal maximum emerged to Nogo stimuli (to the fifth stimulus in the same location in the Different task and the alternation after four identical stimuli in the Same task). An anterior N2 was characteristic to the Nogo stimuli of the Different task. P3 latency was longer, and it had more anterior distribution to the Nogo stimuli. PMID- 8003589 TI - Changes in the number of active sweat glands (palmar sweat index, PSI) during a distressing film. AB - Changes of the number of active palmar sweat glands (palmar sweat index, PSI) as assessed by the plastic finger-print method were studied in two groups of female students (n = 21 each). In both samples experiments involved an initial adaptation period, several relaxation phases and an activation period (presentation of a movie). The film was shown 10 min earlier in Group 1, for which in turn follow-up was twice as long. Prints for determination of PSI were taken every 2.5 min from the forefinger and ring finger of the left hand, and recordings of SCL, SF (number of spontaneous fluctuations) and HR were made during the corresponding intervals. Both within- and between-groups comparisons showed an increase of PSI during the activation period and a decrease afterwards. Similar effects were observed for SCL, SF and affective and somatic arousal assessed by a state questionnaire. A decrease of PSI and parameters of electrodermal activity during the first measurements indicated an initial reaction to the assessment procedure itself. Both within-subject and between subjects correlations between PSI from both fingers showed high parallel test reliabilities, while correlations with electrodermal variables indicated a common physiological basis. PMID- 8003590 TI - Performance and learning during voluntary control of breath patterns. AB - Fourteen subjects learned to adjust their breath pattern to two target breaths displayed on a video screen, by using visual feedback, during two sessions 24 h apart. These two targets were respectively the smallest and the largest breaths of a ten-breath sample previously recorded from each subject's resting spontaneous breathing. Performances were significantly better for the large than for the small target breath. This cannot be directly inferred from current knowledge related to the control of movement time and amplitude, but rather it may be inferred from the periodic character of breathing, to the higher mental load during the small breath task, or to the presumably different frequencies of target breaths in the whole span of spontaneous breathing. In the second session, performance on the two targets levelled out as a result of learning. PMID- 8003591 TI - Neuroendocrine and psychological effects of restricted environmental stimulation technique in a flotation tank. AB - The restricted environmental stimulation technique or REST is a method of relaxation where the level of environmental sensory inputs is kept very low. A particular REST technique called tank flotation, or flotation REST, consists of 1 h sessions in a tank containing water with a high salt content and maintained at 35.5 degrees C. In this protocol, five normal subjects were studied before and during 2 h after a 60 min flotation REST session and a control session of 60 min in a supine position on a bed. Cortisol, thyreostimulating hormone (TSH), thyroxine (T4), prolactin, melatonin, luteinizing hormone (LH), growth hormone (GH), beta-endorphin, vasopressin (ADH), gamma-aminobutyric acid (GABA) and homovanillic acid (HVA) were measured in plasma. HVA, 5-hydroxy-indoleacetic acid (5-HIAA) and vanylmandelic acid (VMA) were measured in urine. There were no changes in hormones concentrations that could be attributed to flotation REST. The urinary excretion of VMA was lower after the flotation REST session. The psychological consequences of flotation REST were more easily demonstrated than the neuroendocrine changes that are assumed to reflect the state of relaxation. Flotation REST increased subjective levels of sedation and euphoria. The possible mechanisms by which flotation REST induces relaxation are discussed. PMID- 8003593 TI - [Treatment of migraine]. PMID- 8003592 TI - Effect of mental stress throughout the day on cardiac autonomic control. AB - Although many laboratory studies have demonstrated changes in cardiac autonomic control during psychological stress, few have attempted to demonstrate this effect in ambulatory subjects. To address this issue, 24-h electrocardiographic recordings of 33 healthy subjects were analyzed for RR interval and heart period variability (HPV) responses associated with periodic diary entries measuring physical position, negative effect, and time of day. A total of 362 diary entries were made during the 24-h sessions, each in response to a device which signaled on an average of once per hour. HPV was analyzed in the frequency domain, yielding estimates of spectral power in low (LF) and high (HF) frequency bands, as well as the LF/HF ratio. Because of the high correlations of the measures of negative affect (alpha = 0.91), they were combined to create a single index of stress. Multivariate analysis was used to assess the effect of individual subject differences, physical position, and stress on RR interval and HPV. Results revealed significant effects of individual differences, stress, and physical position on RR interval, with increases in stress associated with decreases in RR interval as expected. HF power was significantly lower and the LF/HF ratio significantly higher in the standing compared with the sitting position. Psychological stress was significantly associated with an increase in the LF/HF ratio, suggesting increases in the relative predominance of sympathetic nervous system activity during stressful periods of the day. Overall, these findings suggest that in ambulatory normal subjects, cardiac autonomic control varies throughout the day as a function of self-reported stress. PMID- 8003594 TI - [Primary health care in the crisis of welfare state]. PMID- 8003595 TI - [Care of the population not registered at an urban health center]. AB - OBJECTIVE: To find the work-load involved in caring for a displaced part of the population and its social/health characteristics. DESIGN: Descriptive study lasting a year. SETTING: General medical clinics at an urban Primary Care Centre in Alcorcon (Madrid). PATIENTS: Those users over 14 not registered at the Centre who were attended by the General Practitioners and nursing staff during the study period. MEASUREMENTS AND MAIN RESULTS: During the sampling days 263 non registered patients were attended in on-demand medical consultations, this being 5.58% of the total. 301 home notices were sent out during the year, of which 12.95% were generated by displaced patients. The medical consultations by appointment for this group were 2.3% of the total within the Centre and 15.3% at home. There were no significant differences between the registered and displaced populations regarding the number of referrals to laboratory, radiology or specialists. 21.86% of nurses' pre-arranged home visits were due to the follow-up of displaced patients. The patients in our sample were mostly elderly (82.4%), women (68.6%) and staying for extended periods within our catchment area. A third of them attended for bureaucratic reasons (prescriptions). 58.23% of the remaining consultations were due to chronic pathologies. 18.07% brought with them medical reports or long-treatment booklets. CONCLUSIONS: Caring for the non registered population causes a considerable work-load for the Primary Care team, both because of the number of people and their social/health characteristics. It should be made a requirement that the patient brings medical reports when he/she moves from their customary residence. PMID- 8003597 TI - [Evaluation and improvement of the design of clinical records]. AB - OBJECTIVE: To determine whether applying the methodology of Evaluation and care quality improvement to the design of Clinical Procedures can obtain Procedure documents of high scientific-technical quality, from the structural point of view. DESIGN: A retrospective evaluation study lasting 3 years. SETTING: The Barrio del Carmen Health Centre in Murcia. PATIENTS AND OTHER PARTICIPANTS: The Primary Care team. All those professionals with activities involving Procedure documents. INTERVENTIONS: The object of study is all the documentation of the Procedures produced between 1985 and 1993. The initial evaluation was in 1990. After the detection of deficiencies, corrective measures were proposed. In 1993 there was a re-evaluation, using the compliance scales of the quality of design criteria, which had been previously worked out on the basis both of the most important parts of the Bibliography and the quality specifications stated by the system's internal clients (the professionals). Measurements were made before and after intervention. MEASUREMENTS AND MAIN RESULTS: After the application of the corrective measures arising from the first evaluation, a significant improvement in all the design criteria for the procedures was obtained: the average defects per procedure document fell from 8.26 to 1.85. Three of the procedure documents ended up having no defects, either in structure or formal design (format, design method and document production). CONCLUSIONS: A substantial improvement in the structural quality of the documents for the Procedures developed in our Health Centre was achieved by applying the methodology of evaluation and quality improvement. PMID- 8003596 TI - [Usefulness of physical examination at school]. AB - OBJECTIVE: To evaluate the utility of school health examinations performed at four years of age. DESIGN: Evaluation of the results of school health examinations performed on 5,709 children are presented, with the follow up of selected problems found (overweight, growth failure, strabismus, reduced uncorrected visual acuity, hearing loss, psychomotor development and speech development impairment, hydrocele, cryptorchism, haematuria, dental caries and heart murmur). SETTING: 4-year old kindergarten children assessed in the school health program in the city of Barcelona (Catalonia, Spain). MAIN RESULTS: The examination identified 1,177 suspected defects in 960 children. Through a telephone interview with the families of 745 of these children, it was found that only 34.1% were previously unknown to families. The most frequently unknown problem was dental caries. Professional help was sought for 54.3% of the suspected defects. Only 10.5% of the suspected problems began any sort of treatment. The most frequently treated problems wer previously uncorrected refractive defects of the vision. Families report that 8.2% of the suspected problems improve. CONCLUSIONS: These results suggest that the current health output of school health examinations in our city is modest, and that their cost opportunity should be reviewed. PMID- 8003598 TI - [Giving up tobacco and changes in biological parameters]. AB - OBJECTIVE: To study the modifications in some biological parameters in patients who stop smoking. DESIGN: An analytic observational prospective study. SETTING: Urban Health Centre. PARTICIPANTS: 152 patients included in an intervention project against tobacco addiction. MEASUREMENTS AND MAIN RESULTS: Arterial pressure (systolic and diastolic), weight and base cardiac frequency were determined, using standard procedures at the start and end of the study year on smokers who gave up the tobacco habit and on those who continued smoking. Cessation was validated for those who gave up smoking. A non-significant reduction in arterial pressure, an average reduction of 6 beats per minute (p < 0.05) and an average weight increase of 1.5 kg (p < 0.05) were observed in the ex smokers. CONCLUSIONS: Giving up tobacco produces a benefit not comparable to the light increase in weight observed in the ex-smokers. It would be useful to study whether proper dietary advice could minimise weight gain in recent ex-smokers. PMID- 8003599 TI - [Bowenoid papulosis. Review of 4 cases in a health center]. AB - OBJECTIVE: To check the clinical, histological, evolutionary and therapeutic characteristics of Bowen's Disease. DESIGN: A descriptive study of a crossover type. SETTING: Primary Care and a Dermatology clinic at a Health Centre. PATIENTS: There were 4 adult males, aged between 25 and 31, with pigmented papulosis lesions on their external genitals. Two of them were HIV-positive. MEASUREMENTS AND MAIN RESULTS: Clinical records were used. The diagnosis was confirmed through histological analysis. In all cases the lesions were papulosis, multiple and affecting the external genitals. The patients were clinically controlled until the lesions disappeared. The patients' sexual partners were referred to Gynaecology clinics for examination, but no pathology was found in any of them. CONCLUSIONS: Basic knowledge of Bowen's Disease in Primary Care is important given that it is essential to reach a diagnosis as early as possible, in order to monitor the patient and his partner and so avoid any future complications arising from the pathology's presence, such as tumour processes affecting the uterine cervix. The performance of histological analyses when faced with any suspicious genital lesion must be encouraged, given that this technique is non-aggressive. PMID- 8003600 TI - [Prevalence of the smoking habit among health professionals of La Rioja]. AB - OBJECTIVE: Study of the prevalence of smoking among La Rioja's health professionals. DESIGN: Descriptive study. SETTING: The Autonomous Community of La Rioja. PARTICIPANTS: A random sample of health workers taken from the censuses of their respective Professional Colleges on February 1st, 1988. RESULTS: Of a representative sample of 616 health professionals in La Rioja, 47.9% were current smokers, breaking down into 43.5% habitual and 4.4% occasional smokers. 25.5% of the sample were ex-smokers. There were more women (51.1%) than men (44.0%) smokers. The prevalence of habitual smoking is greater in those people under 35 (57.6%) than in those over this age (32.0%) (p < 0.001). CONCLUSIONS: The results obtained make clear that there is a high prevalence of tobacco addiction in our health environment. These data suggest the need for intensified consciousness raising campaigns aimed at health professionals. PMID- 8003601 TI - [Self application of preventive measures and opinion about applying them to the population at the health centers of Cantabria]. AB - OBJECTIVE: To establish the degree of fulfillment of preventive measures and health promotion recommended by the Spanish Society of Family and Community Medicine for medical staff; to determine the opinion for medical staff about the application to these preventive measures in the general population and to analyse the relationship between the self application and the recommendation to the population. DESIGN: Cross-sectional observational through questionnaire. SETTING: Health Centers in Cantabria. PARTICIPANTS: Medical staff of Health Centers. MEASUREMENTS AND MAIN RESULTS: A response of 67.9% (146 out of 215) was obtained. The results of the self application had been: smokers, 35.6%; know their TA, 89.5%; know their weight, 99.3%; know their cholesterol, 81.5%; tetanus vaccinated, 41.4%; influence vaccinated, 33.6%; hepatitis B vaccinated, 38.6%; consume alcohol in excess, 5.6%; make breasts annual exploration, 44.4%; mammography, 33.0%; cervical cytology, 73.1% protected against german measles, 87.2%. The opinion of the medical staff about the application of the preventive measures in the general population of was positive in more of 90% the respondent. We found a significant relation (p < 0.01) between self application and recommendations to the population; and the population recommendation also showed an inverse relationship with the number of years of experience in First Aid (p < 0.01). However, the statistical was low for these variables (0.2). CONCLUSION: The self application of the preventive measures in the Health Centers of Cantabria is in general better than in other Spanish regions and although, we found relations between self application and recommendation to the population the statistics potency was low for this variable. PMID- 8003602 TI - [Acceptance of recombinant hepatitis B vaccine by health personnel]. AB - OBJECTIVE: To find the level of acceptance of the recombinant anti-Hepatitis B vaccination by our area's health staff as well as the reasons why some staff had not been vaccinated. DESIGN: A descriptive study of a crossover type (cross sectional), with data-gathering by means of a self-administered questionnaire. SETTING: Primary Care teams (PCT) in Asturias Area III (Aviles county) and their referral hospital. PARTICIPANTS: 379 health workers (115 from PCT and 264 from the referral hospital) from Asturias Area III, with a simple random sample selection based on the Area's staff lists. MEASUREMENTS AND MAIN RESULTS: 34 of the subjects under study stated that they were immune prior to vaccination. Out of those without immunity, and therefore available for vaccination, 77.1% (80.9% doctors, 88.5% nurses and 57.7% auxiliary staff) accepted vaccination. There were no significant differences between PCT and hospital, except for auxiliary staff, for whom there were more vaccinations in the hospital. Doctors and nurses, independently of the work centre, were vaccinated to a significantly greater extent than the auxiliary staff. Among those who were not vaccinated, the main reason for refusing the vaccination was laziness or lack of interest (36.1% in PCT and 44.1% in hospital). CONCLUSIONS: Hepatitis B vaccination in our areas is greater among health staff most exposed to risk of contagion. Despite the high vaccination rate, an important number of staff remain non-vaccinated, mainly because of their own lack of interest. This must be borne in mind when vaccination programmes are being designed. PMID- 8003603 TI - [Sumatriptan in the treatment of acute migraine: its role in primary health care]. PMID- 8003604 TI - [Family and community medicine: a university education subject]. PMID- 8003605 TI - [Primary health care physician and Parkinson's disease]. PMID- 8003606 TI - [Errors in Information Systems of Primary Care Centers: a problem to be kept in mind]. PMID- 8003607 TI - [Attitudes of primary health personnel towards HIV infected patients]. PMID- 8003609 TI - [Characteristics of the consultation record]. PMID- 8003608 TI - [Delay in the care of acute myocardial infarct: prospects of prehospital thrombolysis]. PMID- 8003610 TI - Effect of mycobacterial infection in the lupus-prone MRL/lpr mice: enhancement of life span of autoimmune mice, amelioration of kidney disease and transient decrease in host resistance. AB - We have used the MRL/lpr murine model of spontaneous lupus to investigate three questions in infection immunity: (1) does mycobacterial infection have any effect on the mortality of the autoimmunity-prone lpr mice?; (2) does the infection modify the progression of kidney disease of lpr lupus?; and (3) does the lpr gene change the resistance of mice to mycobacteria? Experimental infections were induced by intraperitoneal inoculation of 10(7) viable bacilli of Mycobacterium avium in 3 months old MRL/lpr mice and also in congeneic MRL/+ mice (lacking the lpr gene). MRL mice were sacrificed 1, 2.5 and 4 months after the M. avium injection. We found that infection caused lowering of urine protein concentration in lpr mice as compared with age-matched lpr controls. Mycobacteriosis also induced a marked decrease in the mortality of lpr animals, e.g. 85% of infected lpr mice reached the age of 7 months whereas only 10% of control lpr mice reached the same age. MRL/lpr mice showed, after 1 and 2.5 months of infection, higher mycobacterial loads than the congeneic non-lpr MRL mice; after 4 months of infection, however, differences in M. avium loads between the two groups of MRL mice became not statistically significant. We conclude that: (1) mycobacterial infection increases the life span of lpr mice; (2) the infection slows down the progression of kidney disease in the lupus-prone lpr animals; (3) the autoimmunity gene lpr is associated with a transient decrease in host resistance to mycobacteria. PMID- 8003611 TI - Expression of c-myc, c-myb, and c-sis in fibroblasts from affected and unaffected skin of patients with systemic sclerosis. AB - We examined c-sis, c-myc, and c-myb proto-oncogene expression in fibroblasts cultured from affected and unaffected skin of patients with systemic sclerosis (SSc), and from healthy donor skin. Total cellular RNA from cultured dermal fibroblasts was used in slot blot analysis and scanning densitometry or phosphorimaging to quantify steady-state levels of proto-oncogene mRNAs. PDGF B chain levels in culture supernatants of fibroblasts were determined by ELISA. Our results demonstrate that steady-state levels of c-myc and c-myb mRNA were elevated 1.5- to 5.6-fold in intralesional fibroblasts from SSc patients as compared to other cells examined. Levels of c-sis mRNA and PDGF-B protein were comparable regardless of source. Elevated c-myc and c-myb expression may be indicative of, and may contribute to, fibroblast activation in SSc. PMID- 8003612 TI - Expression of the addisonian autoantigen in human adrenal tumors. AB - Sera of patients with Addison's disease contain autoantibodies recognizing antigen(s) in the adrenal cortex. In the present study we have examined the antigen expression in normal (n = 6) and pathological human adrenal tissues (n = 24) and also in the human steroid-producing adrenocortical cell line NCI-H295. Sera from two patients with Addison's disease were selected as they strongly stained the human adrenal gland and identified a 54 kDa autoantigen previously demonstrated as 21-hydroxylase. These sera reacted with normal human adrenal cortex (n = 6), all hyperplasias (n = 5) and all the adrenocortical cancers (n = 9), whereas slight or no reactivity was observed in the adenomas without any detectable excess of peripheral steroids (n = 4). Both patient sera reacted in an identical manner with each tissue specimen and they also reacted strongly with the steroid-producing cell line. The data demonstrate that the expression of the Addisonian autoantigen correlates with the functional activity of adrenocortical neoplasms. Furthermore they suggest, that immunohistochemical stainings for steroid-producing enzymes may be clinically useful in the characterization of adrenal lesions. PMID- 8003614 TI - Suppression of collagen induced arthritis by oral administration of type II collagen: changes in immune and arthritic responses mediated by active peripheral suppression. AB - The oral administration of CII by gavage to WA/KIR rats before a conventional arthritogenic challenge with bovine CII in FIA reduced the incidence (by 23%) and delayed the onset of collagen-induced arthritis in about 50% of the animals. Selective changes in B cell and T cell responses to CII in animals treated this way are interpreted to indicate a state of tolerance or hyporesponsiveness to CII. Tolerant animals made less serum antibody, to bovine and rat CII, of the IgG2b isotype and more of the IgG1 isotype. Phenotypic and functional analysis of peripheral lymph node cells showed that those from tolerized animals expressed less MHC Class II, proliferated less and secreted less IgG2b anti-CII antibody in response to stimulation in vitro with CII when compared with cells from non tolerant animals. However, this depression of the immune responses to CII seen in vitro was overcome when the cells were incubated with increasing amounts of CII. Tolerance could be transferred to normal animals. Spleen cells, and nylon wool filtered splenic T cells (but not mesenteric lymph node cells) adoptively transferred hyporesponsiveness to normal recipients which were then less susceptible to collagen-induced arthritis. Transfer of serum from gavaged animals did not modify the susceptibility of normal recipients to arthritis. Spleen cells from gavaged animals suppressed proliferative and antibody responses in co cultures in vitro with lymph node cells from animals immunized with CII in FIA. The suppressive spleen cell population contained more cells expressing MHC Class II, in both the CD8+ and CD4+ populations. These studies show that the oral administration of CII alters the subsequent immune response to the arthritogenic challenge and indicate that this oral tolerance of CII is due, not to clonal deletion or anergy, but rather to an antigen-driven active suppression mechanism that affects both T cells and B cells, most likely through the action of regulatory cytokines IL-4, IL-10 and TGF beta. PMID- 8003613 TI - Modulation of beta-cell activity and its influence on islet cell antibody (ICA) and islet cell surface antibody (ICSA) reactivity. AB - Insulin-dependent diabetes mellitus (IDDM) is associated with the formation of autoantibodies against different antigens in the islets of Langerhans, so-called islet cell antibodies (ICA). The expression of a major autoantigen, the beta-cell specific enzyme glutamic acid decarboxylase (GAD), is glucose-dependent in vitro and correlated to insulin release in vitro. In this study the expression of islet autoantigens was examined in vivo and the relationship between beta-cell function and islet cell surface antibody (ICSA) reactivity was tested. Rats were fed for 10 days with glipizide or diazoxide, in order to stimulate or inhibit insulin release, respectively. Frozen sections of pancreata were incubated with ten ICA positive IDDM sera and analyzed by indirect immunofluorescence. Two sera with a "beta-cell restricted" staining, five with an "all-islet cell" staining and three with a "mixed" pattern were employed. In all three groups, the highest end-point titres were obtained when pancreata of rats treated with glipizide were used. Intermediate titres were seen in control animals and the lowest titres were observed on pancreata from diazoxide-treated rats, regardless of the serum used. In contrast to these observations, no correlation between ICSA reactivity and islet cell activity could be demonstrated. Conflicting results concerning ICSA in previous reports and our failure to show a glucose regulation of ICSA reactivity, indicate that ICSA is a phenomenon with a low degree of specificity.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8003616 TI - Autoimmune thrombocytopenic purpura in pregnancy: maternal risk factors predictive of neonatal thrombocytopenia. AB - Pregnancy in ATP women is not unusual. The problem of this association concerns the possibility of disease transmission to the fetus due to the crossing of maternal antiplatelet antibodies through the placenta. Maternal risk factors predictive of neonatal thrombocytopenia, can be identified as follows: severe thrombocytopenia, previous splenectomy, high titre of PA-IgG and/or SPB-IgG. In 63 pregnancies in ATP patients, we have evaluated whether the above maternal risk factors, considered in the third trimester, can provide useful criteria for the prediction of neonatal thrombocytopenia. In the third trimester, the distribution of maternal risk factors was as follows: 0 in 7 cases, 1 in 27 cases, 2 in 15 cases, 3 in 12 cases, 4 in 2 cases. From a statistical evaluation, the neonatal platelet values and the maternal risk factors seem inversely correlated (r 0.437; p = 0.0005). In particular, neonatal and maternal platelet count correlated positively (r = 0.249; p = 0.025); moreover, neonatal platelet count correlated negatively with Splenectomy (r = -0.209; p = 0.05), PA-IgG (r = 0.401; p < 0.0005) and SPB-IgG (r = -0.338; p < 0.005). We tried to apply a multiple regression model for all the above parameters which appears statistically significant (p = 0.001); the variability was about 30%. This regression model could be validated if applied to a larger number of cases, and it could represent an alternative to the invasive methods used for the diagnosis of neonatal thrombocytopenia. PMID- 8003615 TI - Experimental autoimmune prostatitis (EAP): enhanced release of reactive oxygen intermediates (ROI) in peritoneal macrophages. AB - The metabolic state of peritoneal macrophages is defined quantitatively for spontaneous ROI release and compared with those produced after cell contact with phorbol myristate acetate (PMA) or zymosan (OZ) particles. Peritoneal exudate cells (PEC) from EAP animals spontaneously released significantly more ROI than cells from controls rats, indicating that mononuclear phagocytes from autoimmune rats were more activated than populations cells arising from rats injected with BSA, with CFA or non-injected. These findings could indicate an in vivo activation state in PEC from autoimmune rats different from that obtained with heterologous antigens or CFA immunization procedures. The release of ROI induced after in vitro stimulus was, in general, higher in cells from autoimmune than in BSA or CFA treated rats. This differential responsiveness between the MAG, BSA and CFA injected macrophage populations could indicate that during the autoimmune process the autoantigen/s could amplify the inflammatory response triggered by them. Although release of oxygen metabolites represents only one of many potential mechanisms of tissue injury, this together with the lesions observed in the prostate gland indicate that oxygen radicals could be involved in this autoimmune disease. PMID- 8003617 TI - Analysis of the V kappa III variable regions of polyclonal rheumatoid factors arising during Epstein Barr virus induced infectious mononucleosis. AB - The mechanisms that govern autoantibody production are still under debate. In particular, auto-antibodies can appear as a consequence of a polyclonal activation of B cells or as a consequence of an antigen driven B cell expansion. The molecular analysis of the variable regions of auto-antibodies arising during different clinical situations can help to understand the origin of auto antibodies. We recently described the main light chain variable regions of polyclonal rheumatoid factors occurring during rheumatoid arthritis and suggested that the mutation pattern of these regions could reflect an antigen driven process. Using the same approach, we now report the molecular analysis of the same light chain variable region containing a VKIII segment of rheumatoid factors originating from a polyclonal activation of B cells during an in vivo Epstein Barr virus infection, infectious mononucleosis. The cDNA derived from rheumatoid factor synthetizing cells were amplified by two sets of polymerase chain reaction. The amplified products were cloned in M13mp19 phages and sequenced. The nucleotide analysis of the VKIII containing VK regions shows that: 1) the rheumatoid factor activity is associated with the 3 VKIII genes (Kv 325, Kv 328 and Vg) already known to encode for monoclonal and polyclonal rheumatoid factors, 2) there is a preferential use of Kv 328 and Vg, each one of these genes being poorly mutated, 3) the CDR mutation rates of these genes is no higher than the framework mutation rates, 4) there is a restriction of the JK usage; Kv 328 derived gene segments rearrange exclusively with JK1, Vg preferentially rearranges with JK1 and JK4. These results mainly suggest that naturally occurring polyclonal activation of autoreactive B cells produces poorly mutated autoantibodies. PMID- 8003618 TI - Immunopathogenesis of systemic sclerosis: possible role of retroviruses. PMID- 8003619 TI - On higher buckling transitions in supercoiled DNA. AB - A combination of detailed energy minimization and molecular dynamics studies of closed circular DNA offers here new information that may be relevant to the dynamics of short DNA chains and/or low superhelical densities. We find a complex dependence of supercoiled DNA energies and geometries on the linking number difference delta Lk as physiological superhelical densities (magnitude of sigma approximately 0.06) are approached. The energy minimization results confirm and extend predictions of classical elasticity theory for the equilibria of elastic rods. The molecular dynamics results suggest how these findings may affect the dynamics of supercoiled DNA. The minimization reveals sudden higher order configurational transitions in addition to the well-known catastrophic buckling from the circle to the figure-8. The competition among the bending, twisting, and self-contact forces leads to different families of supercoiled forms. Some of those families begin with configurations of near-zero twist. This offers the intriguing possibility that nicked DNA may relax to low-twist forms other than the circle, as generally assumed. Furthermore, for certain values of delta Lk, more than one interwound DNA minimum exists. The writhing number as a function of delta Lk is discontinuous in some ranges; it exhibits pronounced jumps as delta Lk is increased from zero, and it appears to level off to a characteristic slope only at higher values of delta Lk. These findings suggest that supercoiled DNA may undergo systematic rapid interconversions between different minima that are both close in energy and geometry. Our molecular dynamics simulations reveal such transitional behavior. We observe the macroscopic bending and twisting fluctuations of interwound forms about the global helix axis as well as the end over-end tumbling of the DNA as a rigid body. The overall mobility can be related to magnitude of sigma and to the bending, twisting, and van der Waals energy fluctuations. The general character of molecular motions is thus determined by the types of energy minima found at a given delta Lk. Different time scales may be attributed to each type of motion: The overall chain folding occurs on a time scale almost an order of magnitude faster than the end-over-end tumbling. The local bending and twisting of individual chain residues occur at an even faster rate, which in turn correspond to several cycles of local variations for each large-scale bending and straightening motion of the DNA. PMID- 8003620 TI - The interaction of ellipticine derivatives with nucleic acids studied by optical and 1H-nmr spectroscopy: effect of size of the heterocyclic ring system. AB - The DNA interaction of derivatives of ellipticine with heterocyclic ring systems with three, four, or five rings and a dimethylaminoethyl side chain was studied. Optical spectroscopy of drug complexes with calf thymus DNA, poly[(dA-dT).(dA dT)], or poly[(dG-dC).(dG-dC)] showed a 10 nm bathochromic shift of the light absorption bands of the pentacyclic and tetracyclic compounds upon binding to the nucleic acids, which indicates binding by intercalation. For the tricyclic compound a smaller shift of 1-3 nm was observed upon binding to the nucleic acids. Flow linear dichroism studies show that the geometry of all complexes is consistent with intercalation of the ring system, except for the DNA and poly[(dG dC).(dG-dC)] complexes of the tricyclic compound, where the average angle between the drug molecular plane and the DNA helix axis was found to be 65 degrees. One dimensional 1H-nmr spectroscopy was used to study complexes between d(CGCGATCGCG)2 and the tricyclic and pentacyclic compounds. The results on the pentacyclic compound show nonselective broadening due to intermediate chemical exchange of most oligonucleotide resonances upon drug binding. The imino proton resonances are in slow chemical exchange, and new resonances with upfield shifts approaching 1 ppm appear upon drug binding, which supports intercalative binding of the pentacyclic compound. The results on the tricyclic compound show more rapid binding kinetics and very selective broadening of resonances. The data suggest that the tricyclic compound is in an equilibrium between intercalation and minor groove binding, with a preference to bind close to the AT base pairs with the side chain residing in the minor groove. PMID- 8003621 TI - Nmr and molecular modeling investigations of the neuropeptide bradykinin in three different solvent systems: DMSO, 9:1 dioxane/water, and in the presence of 7.4 mM lyso phosphatidylcholine micelles. AB - The linear nonapeptide hormone bradykinin (Arg1-Pro2-Pro3-Gly4-Phe5-Ser6-Pro7 Phe8-Arg9) is involved, either directly or indirectly, in a wide variety of physiological processes, particularly pain and hyperanalgesia. Additional evidence suggests that bradykinin also plays a major role in inflammatory response, asthma, sepsis, and symptoms associated with the rhinoviral infection. It has long been speculated that a beta-turn at the C-terminus of bradykinin plays a major role in the biological activity of the neuropeptide. The beta-turn forming potential of bradykinin in three vastly different local chemical environments, DMSO, 9:1 dioxane/water, and in the presence of 7.4 mM lyso phosphatidylcholine micelles, was investigated using two-dimensional homonuclear nmr experiments coupled with simulated annealing calculations. The results of these investigations show that in all three systems residues 6-9 of the C terminus adopt very similar beta-turn like structures. These results suggest that the beta-turn at the C-terminus of bradykinin is an important secondary structural feature for receptor recognition and binding. PMID- 8003622 TI - Relaxed-residue conformational mapping of the three linkage bonds of isomaltose and gentiobiose with MM3 (92). AB - Isoenergy surfaces were calculated for the alpha- and beta-anomers of isomaltose and gentiobiose, based on 46,656 conformers for each disaccharide. Low-energy regions exist for each of the three staggered positions about the C-5'-C-6' bonds, and known crystal structures lie in two of these regions. As expected, the molecular partition function showed greater flexibility for these three-bond linked disaccharides than for comparable two-bond-linked structures. A model miniature crystal of gentiobiose accounts for most of the remaining structural differences between the modeled isolated molecule and the crystal structure. Based on models of isolated molecules of isomaltose and gentiobiose, the predicted Boltzmann-weighted nmr coupling constants were satisfactory, as were predicted optical rotations for gentiobiose. PMID- 8003623 TI - Helix formation by the phospholipase A2 38-59 fragment: influence of chain shortening and dimerization monitored by nmr chemical shifts. AB - The solution structure of a peptide fragment corresponding to the 38-59 region of porcine phospholipase A2 has been investigated using CD, nmr chemical shifts, and nuclear overhauser effects (NOEs). This isolated fragment of phospholipase forms an alpha-helix spanning residues 38-55, very similar to the one found in the native protein, except for residues 56-58, which were helical in the crystal but found random in solution. Addition of triflouroethanol (TFE) merely increased helix population but it did not redefine helix limits. To investigate how the folding information, in particular that concerning eventual helix start and stop signals, was coded in this particular amino acid sequence, the helices formed by synthetic peptides reproducing sections of this phospholipase 38-59 fragment, namely 40-59, 42-59, 38-50, and 45-57, were characterized using NOEs and helix populations quantitatively evaluated on different peptide chain segments using nmr chemical shifts in two solvents (H2O and 30% TFE/H2O). A set of nmr spectra was also recorded and assigned under denaturing conditions (6M urea) to obtain reliable values for the chemical shifts of each peptide in the random state. Based on chemical shift data, it was concluded that the helix formed by the phospholipase 38-59 fragment was not abruptly, but progressively, destabilized all along its length by successive elimination of residues at the N end, while the removal of residues at the C end affected helix stability more locally and to a lesser extent. These results are consistent with the idea that there are not single residues responsible for helix initiation or helix stability, and they also evidence an asymmetry for contributions to helix stability by residues located at the two chain ends. The restriction of molecular mobility caused by linking with a disulphide bridge at Cys 51 two identical 38-59 peptide chains did not increase helix stability. The helix formed by the covalently formed homodimer was very similar in length and population to that formed by the monomer. PMID- 8003624 TI - Unusually stable beta-sheet formation in an ionic self-complementary oligopeptide. AB - A 16-residue amphiphilic oligopeptide (EAK16) with every other residue alanine and also containing glutamic acid and lysine (Ac-NH-AEAEAKAKAEAEAKAK-CONH2) is able to form an unusually stable beta-sheet structure. The beta-sheet structure is stable at very low concentrations in water and at high temperatures. Various pH changes at 1.5, 3, 7, and 11 had little effect on the stability of the beta sheet structure. The beta-sheet structure was not altered significantly even in the presence of 0.1% SDS, 7 molar guanidine hydrochloride, or 8 molar urea. One of the structural characteristics of the EAK16 is its ionic self-complementarity in that ionic bonds and hydrogen bonds between Glu and Lys can form readily between two oligopeptide beta-sheet structures. This structural feature is probably one of the factors that promotes its extreme stability. This is the first example of such an extended ionic self-complementarity in a protein structure. EAK16 and its related peptides may have applications as useful biomaterials. It also offers a good model for studying the mechanism of beta sheet formation. Because the oligopeptide can self-assemble to form a membranous structure, it may have relevance to origin of life research. PMID- 8003625 TI - Biophysical studies on fragments of the alpha-factor receptor protein. AB - The receptor for the alpha-factor mating pheromone of the yeast Saccharomyces cerevisiae consists of 431 amino acid residues and is a member of a family of membrane proteins predicted to have seven transmembrane helices. Fragments of the receptor corresponding to two of the transmembrane helices [residues 246-269 (M6) and 273-302 (M7)], two of the interhelical loops [residues 107-125 (E2) and 191 206 (E3)], and to a portion of the carboxyl terminus [residues 350-372 (CT)] were synthesized using solid-phase methodologies and purified to near homogeneity. CD was used to characterize the secondary structure of these peptides in trifluoroethanol (TFE), in TFE/water mixtures, in sodium dodecyl sulfate (SDS), and in the presence of dimyristoyl phosphatidylcholine (DMPC) liposomes. In TFE, M6 and M7 exhibited CD spectra consistent with highly helical peptides, whereas CT was partially helical. In contrast, E2 and E3 were either disordered or aggregated in this solvent. M6 did not partition well into DMPC vesicles whereas M7 remained helical. Both M6 and M7 assumed helical conformations in 25 mM SDS. The loop peptides and the carboxyl terminus peptide were either in a beta structure or disordered in the presence of lipid. These findings represent the first biophysical evidence for conformations assumed by specific segments of the STE2 receptor protein. PMID- 8003627 TI - Functionally distinct high and low molecular weight species of channel catfish and mouse IL-1. AB - Culture supernatants from channel catfish monocytes exhibit IL-1-like activity for mouse and catfish T cells. Gel filtration analyses of these supernatants indicated that there were at least two forms of IL-1-like activity, i.e. a high molecular weight form (70 kD) active on channel catfish, but not mouse, T cells and a low molecular weight form (approximately 15 kD) with activity for mouse, but not catfish, T cells. Both sizes of catfish IL-1 exhibited alpha and beta determinants as shown by Western blot analyses using antisera to human IL-1 alpha and IL-1 beta. Further evidence for the IL-1 nature of these molecules was obtained by antibody inhibition assays wherein antisera to human IL-1 alpha and IL-1 beta each neutralized approximately 50% of the catfish activities, were additive to some extent, and could be reversed by the addition of the proper human recombinant protein. In culture supernatants of murine P388D1 cells functional activities for catfish and mouse T cells were found only in high and low molecular weight fractions, respectively. Western blots with antiserum to mouse IL-1 alpha revealed IL-1 determinants in both high and low molecular fractions of the mouse cell culture supernatants. These data suggest that catfish and mammalian IL-1 molecules may be quite similar with the caveat being that functional activity for catfish T cells requires a large protein, presented as an aggregate, a polymer, or simply a single chain 70 kD protein. However, only the low molecular weight forms (30 and 15 kD) are active on mouse T cells. PMID- 8003626 TI - The mouse interleukin 1 receptor antagonist protein: gene structure and regulation in vitro. AB - The interleukin 1 receptor antagonist (IL-1ra) protein is an inhibitor of the pro inflammatory cytokine interleukin 1. We have sequenced the mouse gene encoding the monocyte form of IL-1ra (IL-1rn) and compared it with the sequence of the human homologue. In addition to high levels of similarity between the coding regions of the two genes, portions of the introns show surprisingly high levels of identity. In order to develop an in vitro model system to investigate the regulation of IL-1ra induction, three differently responding mouse macrophage cell lines were stimulated with lipopolysaccharide. The kinetics and magnitude of IL-1ra mRNA accumulation was cell-line specific indicating that IL-1ra synthesis in response to inducing agents varies according to the phenotype of the cell. Analysis of the relative transcription rate and the half life of the mouse IL-1ra mRNA indicate that IL-1ra mRNA accumulation in macrophages following LPS treatment is due primarily to an increase in transcription rate rather than to increased stability. PMID- 8003628 TI - IL-2 mRNA levels and degradation rates change with mode of stimulation and phorbol ester treatment of lymphocytes. AB - Transient expression of interleukin 2 (IL-2) in activated T lymphocytes may be due to transcriptional and post-transcriptional regulation. As incubation of lymphocytes with the phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA) prior to mitogenic stimulation results in decreased levels of IL-2 mRNA, we asked if IL-2 mRNA stability was affected. We found that in TPA-treated cells, IL-2 mRNA was degraded more rapidly than in untreated ones whether the mitogenic stimulus was Concanavalin A (Con A), Con A plus TPA, or TPA plus ionomycin. The degradation was blocked if the TPA pre-incubation included cycloheximide. In contrast, when TPA was included as a co-mitogen, i.e. added at the same time as the mitogen, the IL-2 mRNA levels and stability significantly increased. Compared to the levels found in Con A stimulated cells, TPA plus Con A increased IL-2 mRNA levels by as much as 20-fold and the half-life by 5-fold. TPA plus ionomycin increased the message levels at least 100-fold and half-life by nearly 10-fold. These effects on IL-2 mRNA were not general because IL-2 receptor mRNA stability was not changed even though it also is transiently expressed during the course of lymphocyte activation. PMID- 8003629 TI - Interleukin 1 activity in haemolymph from strains of the snail Biomphalaria glabrata varying in susceptibility to the human blood fluke, Schistosoma mansoni: presence, differential expression, and biological function. AB - Cytokines control many of the steps in the complex pathways of immune and inflammatory responses in mammals. Recent reports also indicate that some invertebrates may produce cytokines such as interleukin 1 (IL-1). Certain strains of the snail, Biomphalaria glabrata (intermediate host for the human blood fluke, Schistosoma mansoni), possess a soluble plasma factor that stimulates the haemocyte-mediated killing of larval schistosomes, making them resistant to infection. In this study, we have sought to determine whether these snails possessed IL-1 in their plasma, and whether this cytokine was associated with resistance of B. glabrata to S. mansoni. Plasma from susceptible (M-line) and resistant (10-R2, 13-16-R1) strains of B. glabrata that had been unexposed or exposed to S. mansoni were tested for the presence of IL-1-like activity. Experiments employing both a bioassay and an immunoassay indicated that an IL-1 like molecule was present, in varying quantities, among the snail strains. Further, plasma IL-1 levels were significantly affected by exposure to S. mansoni, with levels dropping in M-line and 10-R2 snails, but increasing in the 13-16-R1 strain. However, both resistant strains maintained significantly higher IL-1 levels than M-line snails. Recombinant, human IL-1 (rhIL-1) was shown to prime haemocytes from both resistant snail strains for superoxide production, but had no effect on haemocytes from susceptible B. glabrata. Moreover, the addition of an IL-1 receptor antagonist protein (IRAP) eliminated this priming effect. Priming with rhIL-1 and/or IRAP had no effect on phagocytosis rates in any of the snail strains tested.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8003630 TI - Species-specificity of monocyte chemotactic protein-1 and -3. AB - The present study was aimed at defining the activity of human and mouse monocyte chemotactic protein-1 (MCP-1) on homologous and heterologous mononuclear phagocytes. Human natural and recombinant MCP-1 and mouse natural MCP-1/JE were tested as chemoattractants on human blood monocytes and mouse peritoneal macrophages. The human and murine cytokines were equiactive on human monocytes. Human MCP-1 was active on mouse macrophages but the maximal chemotactic effect elicited was about half that of human cells or of mouse MCP-1/JE or of reference chemoattractants. Human MCP-3, a recently identified member of the C-C chemokine family, with high sequence similarity to MCP-1/JE, was also active on mouse mononuclear phagocytes, though less so than mouse MCP-1/JE. These results caution against under-estimating the potential of MCPs when the human chemokines are applied in mice. PMID- 8003631 TI - Detection of monocyte chemotactic and activating factor (MCAF) in normal blood and urine using a sensitive ELISA. AB - We developed a highly sensitive enzyme-linked immunosorbent assay (ELISA) for human monocyte chemotactic and activating factor (MCAF), an inflammatory cytokine that plays an important role in the recruitment of blood monocytes to areas of inflammation. The ELISA, which is based on a sandwich method using two newly developed monoclonal antibodies, could quantitatively detect MCAF in the range between 2.5 pg/ml (50 fg/sample) to 300 pg/ml after incubation for a total of 2 h, and showed no cross-reactivity with various structurally-related IL-8 superfamily proteins. It was not affected by blood or urine components non specifically, and thus was directly applicable to clinical specimens. When serum and urine samples from healthy subjects were measured, they all turned out to contain detectable levels of MCAF (more than 30 pg/ml). By gel-filtration column chromatography analysis, MCAF in the body fluids was eluted as a single peak at the position corresponding to the molecular weight of 10 kD, suggesting that it exists as a monomer form, free from carrier proteins. The established ELISA here is expected to be effectively used for the further investigations on the relationship of MCAF with various inflammatory diseases. PMID- 8003632 TI - Interaction between oncostatin M, interleukin 1 and prostaglandin E2 in induction of IL-6 expression in human fibroblasts. AB - The role of Oncostatin M (OM), a monocyte/macrophage and T-cell product, in regulating IL-6 expression in fibroblasts of lung or synovial origin was examined in vitro. Although by itself OM had a minimal effect on enhancing IL-6 production by fibroblasts, in combination with IL-1 alpha or PGE2, OM addition resulted in a dose-dependent synergistic enhancement of IL-6 production. This synergistic effect with either IL-1 alpha (5 ng/ml) or PGE2 (10(-7) M) was clearly evident at concentrations of OM of 10, 20 or 50 ng/ml. Levels of IL-6 resulting from OM and IL-1 alpha stimulation could be reduced by indomethacin (10(-6) M) and restored again by also adding PGE2. Northern blots probed for IL-6 mRNA showed cooperative enhancement of steady state levels at 18 hours of stimulation by OM and IL-1 alpha, or OM and PGE2. Probing for mRNA of the metalloproteinase inhibitor TIMP-1 showed that stimulation by OM, IL-1 alpha or PGE2 enhanced TIMP-1 levels. However, OM (alone) or PGE2 or both combined did not elevate the metalloproteinase stromelysin-1 mRNA signals. Analysis utilizing a rat IL-6 promoter-luciferase reporter gene construct showed that OM stimulation resulted in activation of transcription that synergistically enhanced IL-1-induced levels of reporter gene expression. These results show that although OM has minor effects on IL-6 production alone, the combination of OM and other mediators result in markedly enhanced IL-6 production by fibroblasts in vitro. PMID- 8003633 TI - Oncostatin M (OSM) inhibits the differentiation of pluripotent embryonic stem cells in vitro. AB - Oncostatin M (OSM) is a cytokine which shares a common gene structure and amino acid sequence similarity with leukemia inhibitory factor (LIF), granulocyte colony-stimulating factor (G-CSF) and interleukin 6 (IL-6), suggesting evolution from a common ancestral gene. These four cytokines share several biological activities including the ability to induce the differentiation of the murine M1 myeloid leukemic cell line. To further define the functional similarities within this family, we have investigated whether OSM can substitute for LIF in the maintenance in vitro of the undifferentiated state of pluripotent embryonic stem (ES) cells. In this study, we demonstrate that human recombinant OSM is similar to LIF in its ability to inhibit the differentiation of MBL-5 murine ES cells cultured in vitro. The level of differentiation was determined by morphological criteria and by the continued expression of the embryonic stem cell-specific surface antigen defined by the ECMA-7 monoclonal antibody. Competition binding studies demonstrate that OSM binds to the LIF receptor on MBL-5 ES cells. Our results implicate OSM as a developmental regulatory factor for embryonic stem cells in vivo. PMID- 8003634 TI - The binding pattern of a neutralizing monoclonal antibody to mutant oncostatin M molecules is correlated with functional activity. AB - Oncostatin M (OM) is a member of the cytokine family that includes leukaemia inhibitory factor (LIF), granulocyte colony stimulating factor (G-CSF), and interleukin 6 (IL-6). We previously reported the characterization of a monoclonal antibody (MAb) to OM, termed OM2, which neutralizes its functional activity. To gain information about the epitope detected by this MAb, we utilized a sandwich enzyme-linked immunoassay (EIA) to examine OM2 binding on a series of mutant recombinant OM molecules generated by site-directed mutagenesis, encompassing amino acid insertions, deletions, or alterations throughout the molecule. Carboxy terminal deletions of a putative amphiphilic alpha helix past residue 185 abrogated binding of the OM2 MAb; alteration of a hydrophobic residue in the helix to a neutral one also prevented antibody binding. Analysis of mutants in which cysteines involved in intrachain disulfide binding were changed to serines revealed that one of two disulphide bonds was essential for OM2 binding. Two mutant molecules containing deletions in the amino-terminal one-fourth of the molecule were not bound by OM2, while a third mutant OM molecule with a C terminal proximal internal deletion outside of the amphiphilic alpha helix was bound. The binding pattern of MAb OM2 to the OM mutant molecules correlated well with their functional activities. The data suggest that residues in both the C terminal alpha helix and N-terminal one-fourth of the molecule are involved in neutralizing antibody binding and functional activity.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8003635 TI - Differential expression of the small inducible cytokines GRO alpha and GRO beta by synovial fibroblasts in chronic arthritis: possible role in growth regulation. AB - Synovial pannus represents a hypertrophic and locally invasive connective tissue response to chronic inflammation that accounts in large part for the periarticular destruction of rheumatoid arthritis. Synovial fibroblasts cultured from rheumatoid synovia have been found to display an increased rate of proliferation and the constitutive expression of collagenases, growth factors, and inflammatory cytokines. The existence in rheumatoid synovium of both a pro inflammatory state and growth dysregulation led us to investigate the expression by synovial fibroblasts of the closely homologous cytokines GRO alpha (gro/MGSA), GRO beta (MIP-2 alpha), and GRO gamma (MIP-2 beta). These cytokines are released by a variety of cell types and display overlapping growth regulatory and pro inflammatory activities. In contrast to expectations, the majority of synovial fibroblast cell lines derived from osteoarthritic or non-inflammatory synovia showed a relative increase in the constitutive expression of GRO alpha and GRO beta when compared to synovial fibroblasts obtained from rheumatoid synovia. Considered together with evidence that GRO alpha is a growth regulator that modulates the expression of metalloproteinase activity, these findings provide evidence for a differential pathway of cytokine activation that may downregulate the proliferative and erosive response to chronic arthritis. PMID- 8003636 TI - Modulation of murine and human interferon-gamma receptor expression by their ligands or phorbol ester. AB - IFN-gamma receptor expression on murine leukaemic L1210-cells has been studied. With the help of a transfected cell-line expressing the heterologous human receptor it was possible to discern receptor-specific properties like internalization from those regulating their expression on the surface. Recombinant IFN-gamma binds specifically to its homologous receptor at 4 degrees C and is rapidly internalized at physiologic temperatures. For this effect to occur, ligand binding to its receptor at 37 degrees C is necessary and sufficient. This notion is confirmed since a reduction in the number of heterologous human IFN-gamma receptors on the murine cell surface occurred exclusively after treatment with human IFN-gamma. Even weak doses of ligand, insufficient to occupy all receptors, led to a pronounced disappearance of binding sites. However, both receptors are simultaneously up-regulated in the presence of TPA, indicating a separate pathway which is not species-specific. Our findings imply that similar elements of the intracellular signal transduction machinery are involved in the control of MuIFN-gamma and HuIFN-gamma receptor expression. The results indicate also that factors involved in binding, internalization, and regulation of receptor gene expression are not species specific. PMID- 8003637 TI - Low-dose dietary L-arginine increases plasma interleukin 1 alpha but not interleukin 1 beta in patients with diabetes mellitus. AB - Oral high-dose arginine supplementation is used for the experimental immunotherapy of tissue trauma and sepsis. Yet the adequate dosage required for immunomodulation has to be established and the toxicity of high-dose arginine has not been fully elucidated. Following a protocol for the treatment of diabetic long-term complications (oral daily doses of 30 mg/kg BW; blind, placebo controlled prospective study with crossing-over design) we studied plasma levels of interleukins 1 alpha (IL-1 alpha) and 1 beta reflecting immunostimulation. Arginine supplementation in 29 patients with diabetes mellitus prompted a 2-fold increase of IL-1 alpha from baseline levels (P < 0.001) while IL-1 beta was unaffected. Implications for the treated panel of diabetic patients could be a reduction of collagen accumulation by enhanced collagenolysis and clearance of advanced-stage non-enzymatic glycosylation products. Based upon our data, low dose arginine protocols for further immunotherapeutical studies should be discussed. PMID- 8003638 TI - Monoclonal antibody 1994-01 (also known as ALVA 42) reported to recognize type II IL-1 receptor is specific for HLA-DR alpha and beta chains. AB - Monoclonal antibody (MAb) 1994-01 has been reported to bind to the human type II Interleukin 1 (IL-1) receptor and in so doing block IL-1 binding in vitro and certain IL-1 mediated responses in vivo. While this antibody binds to a type II IL-1 receptor positive cell line, it can be shown that it does not bind to the type II IL-1 receptor. By direct expression cloning, we have identified two gene products, both of which are required for binding of this antibody. The two proteins are the alpha and beta subunits of the MHC class II antigen HLA-DR. PMID- 8003639 TI - Interleukin 6 gene transcripts are expressed in human atherosclerotic lesions. AB - Factors controlling the proliferation of vascular smooth muscle cells (SMC) are thought to be key elements in the progression of atherosclerosis. We have previously shown that interleukin 6 (IL-6) stimulates the growth of SMC in vitro and that IL-6 gene transcripts are expressed in atherosclerotic lesions of genetically hyperlipidemic rabbits. To understand the involvement of IL-6 in the development of human atherosclerosis, we investigated IL-6 mRNA expression in atherosclerotic arteries from patients undergoing surgical vascularization, utilizing reverse transcription polymerase chain reaction (RT-PCR) and in situ hybridization analyses. In RT-PCR analysis, the atherosclerotic arteries showed 10- to 40-fold levels of IL-6 mRNA expression over the non-atherosclerotic artery. In in situ hybridization analysis, IL-6 gene transcripts were observed in the thickened intimal layer of atherosclerotic lesions. These results strongly suggest the involvement of IL-6 in the development of human atherosclerosis. PMID- 8003641 TI - A possible role for bile acid in the control of methanogenesis and the accumulation of hydrogen gas in the human colon. AB - This study investigated a possible role for primary bile acid in the control of methanogenesis in the human colon. Production of hydrogen and methane was measured in anaerobic faecal cultures derived from faeces of six 'non methanogenic' and three methanogenic healthy humans. Using a sensitive technique for gas measurement, methane was detected in all faecal cultures, including those from 'non-methanogenic' humans. Bile acid inhibited methanogenesis in a dose response fashion in the in vitro 'non-methanogenic' and methanogenic faecal cultures. Inhibition was significant at bile acid concentrations > 0.05%. Methanogenesis correlated with methanogen (methanogenic bacteria) numbers. If this inhibition occurs in vivo, then it would explain much of the epidemiology of non-methanogenesis in humans. From an analysis of net hydrogen production by the faecal cultures, it is inferred that bile acid inhibits other hydrogen-consuming bacteria in addition to methanogens. These in vitro data suggest a major role for bile acid in the accumulation of hydrogen gas in the colon. Possible links between bile acid induced accumulation of gas and irritable bowel syndrome are discussed. PMID- 8003640 TI - Cytokines in liposomes: preliminary studies with IL-1, IL-2, IL-6, GM-CSF and interferon-gamma. AB - A simple, generally applicable method to incorporate cytokine proteins into multilamellar liposomes is presented. A variety of human cytokines including granulocyte-macrophage colony stimulating factor (GM-CSF), interleukins 1 alpha, 2 and 6 (IL-1 alpha, IL-2, IL-6) and interferon-gamma (IFN-gamma) were incorporated into liposomes containing a single saturated synthetic lipid, dimyristoyl phosphatidyl choline (DMPC). Sterile cytokine liposomes were produced by gamma irradiation of DMPC lipid powder prior to use in cytokine liposome synthesis. A highly sensitive and reliable fluorescamine assay to detect microgram quantities of cytokine protein associated with liposomes is also described. When a high lipid:aqueous ratio [e.g. 300 mg DMPC lipid:1.0 ml aqueous cytokine solution] was utilized, aqueous cytokines (1 mg/ml) could be incorporated with efficiencies ranging from 19% (IL-1) to > 80% (IL-2). Combinations of cytokines (e.g. IL-2 + GM-CSF) were also co-incorporated into liposomes. Experiments with IL-2, IL-6, and GM-CSF demonstrated that these cytokines remain stably associated with the DMPC lipid and do not significantly leak from liposomes when stored at 4 degrees C for at least 3 months. Washing IL 6 liposome or GM-CSF liposome preparations reliably increased the proportion of cytokine protein associated with the liposome pellet compared to free cytokine in the supernatant of centrifuged specimens. For example the proportion of GM-CSF associated with the lipid carrier increased from 34.8% (SD 2.6%) in the original preparation to 98.0% (SD 0.6%) after three washes. Differences in the pharmacokinetics of subcutaneous (sc) free GM-CSF and GM-CSF liposomes (14 mcg/mouse) were studied in BALB/c mice. Both free GM-CSF and free GM-CSF mixed with saline loaded liposomes exhibited biphasic pharmacokinetics with very high peak levels 1 and 2 h after sc injection of 14 mcg the rapid decline to very low levels after 24 h. In contrast, sc GM-CSF liposomes provided sustained and stable levels of cytokine in the serum (approximately 100 pg/ml) for 24 h. Intraperitoneal injection of GM-CSF liposomes had > 10-fold more cytokine in the peritoneal wash than free GM-CSF mixed with saline loaded liposomes. In summary, the liposome synthesis procedure described is simple and utilizes a single synthetic lipid to reliably produce sterile cytokine preparations with in vivo depot effects after either sc or ip administration. Furthermore, the method is feasible for quantities of sterile cytokine liposomes sufficient for in vivo experiments. PMID- 8003642 TI - A double-blind, randomized, parallel group study of omeprazole and ranitidine in Korean patients with gastric ulcer. AB - The efficacy of the proton pump inhibitor omeprazole, 20 mg every morning, was compared with that of the H2-receptor antagonist ranitidine, 150 mg every morning and at bedtime, in a double-blind randomized parallel group study in 250 patients with gastric or prepyloric ulcers. At both 4 and 8 weeks, significantly more patients had healed ulcers in the omeprazole group than the ranitidine group, whether the results were analysed on a per-protocol or an intention-to-treat basis. At 4 weeks, 74% of patients in the omeprazole group were healed compared with 51% in the ranitidine group (P = 0.001), and at 8 weeks the corresponding values were 99 and 82% (P = 0.001, per-protocol cohort). Omeprazole treatment and small ulcer size significantly increased the probability of healing, but smoking had no significant effect. Patients in the omeprazole group had significantly fewer occurrences of daytime epigastric pain during the first 4 weeks than the ranitidine group (P = 0.0037), as shown by their diary cards. Both treatments were well tolerated. PMID- 8003643 TI - The pattern of functional and organic disorders in an Asian gastroenterological clinic. AB - The aim of the present study was to determine the pattern of structural and functional disorders encountered in an Asian gastroenterological clinic and to compare this pattern with findings from Western centres. Consecutive new patients (totalling 2384) attending the clinics of two consultant gastroenterologists were studied. Of these, 2141 suffered from gastroenterological problems. One thousand and sixty-three (49.6%) had structural diseases, the commoner ones being liver disease, peptic ulcer, malignancy, haemorrhoids and gallstones. The remainder who were found to have no structural disease (n = 1078; 50.4%) were deemed to have functional disorders including non-ulcer dyspepsia, irritable bowel, simple constipation and functional diarrhoea. The proportions of functional and structural disease were similar to those in the West. Major differences included a higher frequency of hepatoma and a lower frequency of inflammatory bowel disease and gastro-oesophageal reflux in the present series. PMID- 8003644 TI - Antiviral effect of lymphoblastoid interferon-alpha on hepatitis C virus in patients with chronic hepatitis type C. AB - To study the antiviral effect of lymphoblastoid alpha interferon (IFN) on hepatitis C virus (HCV) we conducted a randomized, controlled trial on 80 patients with chronic hepatitis C using three different doses. Patients were randomly assigned to treatment with 1, 3 or 6 million units of lymphoblastoid IFN alpha daily for 2 weeks. To assess the antiviral effect of IFN, the amount of HCV present in the serum was estimated by competitive nested polymerase chain reaction (PCR) before and after 2 weeks of treatment. The multiple logistic analysis was used to evaluate factors associated with virus clearance, adjusting the imbalance in predictive factors among patients. Hepatitis C virus became negative as assessed by nested PCR after therapy in 26, 50 and 63% of patients receiving 1, 3 and 6 mega units, respectively. Hepatitis C virus was cleared more often in patients having initially low (< 10(5)/mL) amounts of virus. No significant decrease in the amount of virus was observed in the untreated, control group. Patients without bridging fibrosis in liver histology and with HCV genotypes other than K1 (type II) tended to respond well. These results indicate that lymphoblastoid IFN-alpha suppresses HCV in a dose dependent manner. Higher initial virus amounts, bridging fibrosis and genotype K1 were factors associated with poor response. PMID- 8003645 TI - Clinical experience in 126 patients with tissue-proved proximal cholangiocarcinoma. AB - The diagnosis and treatment of 126 consecutive patients with tissue-proved cholangiocarcinoma which originates in or proximal to the common hepatic duct was reviewed. They are further divided into the hilar type and peripheral type tumours. The clinical presentations were commonly compatible with the hilar type tumour. However, the accurate pre-operative diagnosis of the peripheral type tumour was difficult because of the frequent association with hepatolithiasis (43.3%) and the high prevalence of hepatocellular carcinoma (HCC) in Taiwan; 25% of these patients underwent surgery for chronic cholangitis and 12.5% for HCC rather than cholangiocarcinoma. Among the 40 (31.7%) patients who had tumour resections, 24 were hilar type and 16 were peripheral type. There were no operative deaths and the mean survival time was 36.1 months (27.9 months for the hilar types, 52.2 months for the peripheral types). Sixty-three (50%) patients with hilar type tumours were only suitable for palliative procedures to relieve the jaundice. The 30-day mortality rate was 50 and 33.3% for the patients who received non-surgical and surgical drainages, but zero for the patients who had surgical bypasses. All the bypass patients experienced > 50% decrease of serum bilirubin, but this effect was obtained in less than half the patients receiving drainage procedures. Surgical resection significantly prolonged the survival (resection vs palliation vs no treatment = 36.1 vs 6.6 vs 3.6 months, P < 0.05), but no survival advantage was achieved in any of the palliative therapies. Five cases with tumour resection survived > 5 years. We conclude that surgical resection offers the best prognosis.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8003646 TI - Relationship between endotoxin antibody levels and portal systemic shunt evaluated by per-rectal portal scintigraphy. AB - The reasons for the high frequency of endotoxaemia in cirrhosis, whether poor liver function or abnormal portal circulation, are not known. Accurate measurement of endotoxin itself is difficult. Instead, in this study an enzyme linked immunosorbent assay was used to measure levels of IgA, IgG and IgM antibodies to endotoxin in patients with chronic liver disease and underlying hepatic viral infection. The relationships between the results and clinical symptoms or the presence of a portal systemic shunt were investigated. The median level of IgA antibodies was not different in patients with chronic hepatitis and those with cirrhosis, and the same was found for IgM, but the median level of IgG antibodies was significantly higher in the patients with cirrhosis. When patients with cirrhosis were grouped by the presence or absence of ascites or hepatocellular carcinoma, no significant difference was observed in any of these antibody levels. However, in cirrhotic patients with varices, the level of IgG antibodies to endotoxin was significantly higher than in patients without varices. For evaluation of the portal systemic shunt, the per-rectal portal shunt index was calculated. There was a significant correlation (R = 0.431, P < 0.001) between the per-rectal portal shunt index and the level of IgG antibodies to endotoxin. That is, the degree of abnormality in the portal haemodynamics was correlated with the level of IgG antibodies to endotoxin in patients with liver disease. PMID- 8003647 TI - Chemical dissolution of gallstones in Taiwan: an in vitro study. AB - To evaluate the potential for the chemical dissolution of gallstones, 480 stones from 214 patients were studied. The stones were obtained via surgery or endoscopically. They were classified into cholesterol-rich mixed stones, brown pigment stones and black stones. The composition of bilirubin and cholesterol was determined by Fourier transformed infrared spectroscopy. Two per cent tetrasodium ethylenediamine acetate (EDTA), dimethylsulfoxide (DMSO) or methyl-tert-butyl ethylene (MTBE) were used to dissolve the stones. To enhance solubility, surfactant polysorbate-20 was used to mix two of the individual three solvents. Methyl-tert-butyl-ethylene was found to have the best dissolution ability (by dry weight) 94, 13.4 and 20% for mixed, brown and black stones, respectively. Dimethylsulfoxide resulted in 13, 14 and 25% dissolution and EDTA 9.5, 13 and 16.5%. In contrast, pure water dissolved 4, 6 and 10.4% of the stones, respectively. A combination of the dissolution agents did not enhance the dissolution rate. In fact, the combination of solvents unexpectedly reduced the solubility of the stones: EDTA/MTBE was 17.5, 6.7 and 16.0%; DMSO/MTBE 43.2, 21.9 and 18.0%; DMSO/EDTA 9.1, 7.0 and 9.6%. In conclusion, cholesterol-rich mixed stones were able to be dissolved using MTBE but results of contact dissolution for gallstones are still far from satisfactory. PMID- 8003649 TI - Long-term prognosis and prognostic factors of liver cirrhosis in the 1980s. AB - The prognosis of 174 patients with cirrhosis during the 1980s (1981-89) was analysed. The estimated survival rates were 87.3% in 3 years and 68.5% in 5 years. During the follow-up period, 58 patients died: 20 of hepatocellular carcinoma (37.7%); 11 of hepatic failure (20.8%); eight of gastrointestinal bleeding (15.1%); and 14 of other causes (26.4%). Multivariate analysis revealed that serum albumin, indocyanine green retention rate at 15 min and white blood cell count were significantly associated with prognosis. The results were also compared to our previous study covering the 1970s (1971-80). The estimated survival rate was significantly improved compared to that during the 1970s (54.3% in 5 years, P < 0.001). In the 1980s, hepatic failure mortality significantly decreased (P < 0.01), and non-liver-related mortality significantly increased (P < 0.05). In summary, the prognosis of cirrhosis has improved in recent years, and changes of death cause and prognostic factors were observed. It was concluded that to evaluate the severity and prognosis of cirrhosis, new indices and appropriate classification were necessary. PMID- 8003648 TI - Relationships between the severity of cirrhosis and haemodynamic values in patients with cirrhosis. AB - The relationship between the severity of cirrhosis and systemic and hepatic haemodynamic values was evaluated in 193 patients with cirrhosis, most of whom were diagnosed with post-necrotic cirrhosis. It was found that the hepatic venous pressure gradient and cardiac output in Pugh's A patients (13.6 +/- 4.8 mmHg and 6.2 +/- 1.6 L/min, mean +/- s.d.) were significantly lower than in both Pugh's B (16.8 +/- 4.3 mmHg and 7.3 +/- 2.1 L/min) and Pugh's C (18.8 +/- 5.5 mmHg and 7.4 +/- 2.3 L/min) patients (P < 0.01), respectively. In contrast, the systemic vascular resistance in Pugh's A patients (1232 +/- 369 dyn/s per cm5) was significantly higher than in both Pugh's B (1016 +/- 345 dyn/s per cm5) and Pugh's C (935 +/- 234 dyn/s per cm5) patients (P < 0.01), respectively. Additionally, not only was there a positive correlation found between Pugh's score and cardiac output and hepatic venous pressure gradient, but a negative correlation was found between Pugh's score and systemic vascular resistance. It was also confirmed that the degree of portal hypertension and the hyperdynamic circulation were more severe in patients with ascites than in those without ascites. However, there were no statistically significant differences in hepatic venous pressure gradient among patients with F1, F2 and F3 esophageal varices (15.7 +/- 4.0, 17.0 +/- 4.8 and 18.0 +/- 4.8 mmHg, respectively). It is concluded that in those patients with cirrhosis, the severity of cirrhosis is closely related to the degree of the hyperkinetic circulatory state and portal hypertension. PMID- 8003650 TI - A two year controlled trial examining the effectiveness of ursodeoxycholic acid in primary biliary cirrhosis. AB - Forty-six patients with primary biliary cirrhosis from a single centre were studied in a randomized placebo-controlled trial to determine the effectiveness of ursodeoxycholic acid (UDCA) over a 2 year period. The two groups were well matched at baseline. For each parameter, by calculating the difference between the median changes with time between the UDCA group and the placebo group, it was found that from entry, with respect to placebo, there were differences between median changes (MCD) favouring the UDCA group in bilirubin (MCD 5 mumol/L [95% confidence interval (CI) 1 to 12] at 1 year and 5 mumol/L (95% CI 1 to 9) at 2 years), alkaline phosphatase MCD 242 iu/L (95% CI 107 to 360) at 1 year and 268 iu/L (95% CI 146 to 424) at 2 years and aspartate aminotransferase MCD 26 iu/L (95% CI 12 to 41) at 1 year and 37 iu/L (95% CI 16 to 64) at 2 years. Within the UDCA group, there was long-term fall in alkaline phosphatase [median fall 116 iu/L (95% CI 93 to 378) at 2 years and aspartate aminotransferase [median fall 18 iu/L (95% CI 6 to 47) at 2 years; however, the major change in bilirubin was a modest rise over 2 years in the placebo group [median rise 2 mumol/L (95% CI 1 to 9)]. Changes in albumin, prothrombin ratio and immunoglobulins were generally minor and not significant.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8003651 TI - The Sun Yat-sen Lecture. The surgical treatment of duodenal ulcer: past, present and future. PMID- 8003652 TI - Diet and duodenal ulcer. PMID- 8003653 TI - Cholera toxin and diarrhoea. PMID- 8003655 TI - Laparoscopic observation of retroperitoneal cystic lymphangioma. AB - A case of retroperitoneal cystic lymphangioma observed laparoscopically is reported. In a 60 year old asymptomatic male patient, an 8 cm multi-loculated cystic lesion was detected incidentally near the splenic hilum with ultrasonography. Endosonography, computed tomography and magnetic resonance imaging revealed the lesion with thin wall and clear fluid. Laparoscopy showed a thin-walled cyst with smooth surface, and straw-coloured clear fluid was observed through the wall. These findings suggested benign aetiology, and seemed to be characteristic of cystic lymphangioma. The tumour was resected, and microscopic examination showed proliferated lymph channels intespersed by lymph follicles. Diagnosis of cystic lymphangioma was established. Laparoscopy seems a useful pre operative method. PMID- 8003654 TI - Two cases of Caroli's disease: diagnosis and management. AB - Caroli's disease is an uncommon congenital malformation involving the intrahepatic bile ducts. This paper reports two cases presenting with biliary tract infection. Diagnosis was established by non-invasive imaging and cholangiography. The infecting organisms were cultured from bile obtained by percutaneous aspiration and the results were used to direct antimicrobial therapy. The role of antibiotics and other management options in preventing recurrent infection is discussed. PMID- 8003656 TI - Small bowel ischaemia in Fabry's disease. AB - A patient with previously diagnosed Fabry's disease and a long history of post prandial abdominal pain died following small bowel infarction. Post-mortem demonstrated Fabry's type deposits in the small vessels and nerves supplying the bowel but in addition, a localized atheromatous stenosis of the superior mesenteric artery. In retrospect, his terminal illness and possibly his chronic symptoms were related to the latter finding. Angioplasty to the superior mesenteric artery may have been of benefit. Mesenteric angiography should be considered in patients with chronic post-prandial pain because large vessel disease may coexist with other a priori pathologies and is imminently treatable. PMID- 8003657 TI - Ethanol consumption by rats is inversely related to hepatic alcohol dehydrogenase activity. AB - Under normal circumstances the rate of hepatic ethanol oxidation and the rate at which ethanol is removed from the blood are dependent on the hepatic activity of alcohol dehydrogenase. It is possible that ethanol metabolism, and thus hepatic alcohol dehydrogenase, could influence ethanol consumption. In this study 11 adult female Wistar rats were provided with 20% ethanol as their sole drinking fluid and ethanol consumption was measured. After a further period of drinking tap water, the hepatic alcohol dehydrogenase activity was determined. A significant inverse relationship was found between the ethanol consumption by the rats and the hepatic activity of alcohol dehydrogenase (P < 0.05). This enzyme could therefore play a role in determining the amount of alcohol an animal will consume. PMID- 8003658 TI - Active microglia, sick astroglia and Alzheimer type dementias. AB - We propose that Alzheimer's disease is initiated by failure of axonal transport. After the neurodegeneration cascade is initiated, microglial and astroglial cells have major roles in directly and indirectly promoting self-sustaining neurodegeneration cycles. This hypothesis makes testable predictions and suggests logical therapies. PMID- 8003659 TI - Hippocampal long-term potentiation in vivo induces translocation of protein kinase C gamma. AB - The possible involvement of the Ca(2+)-dependent protein kinase C (PKC) isoenzymes alpha/beta and gamma in mechanisms of long-term potentiation (LTP) was investigated after tetanic stimulation of the perforant path in vivo. Brief tetanic stimulation of the perforant path resulted in a 150% increase in population spike amplitude recorded from the dentate gyrus synapses in response to test stimuli 5 and 10 min after tetanization. Immunoblot analysis of PKC immunoreactivity in cytosolic and membrane fractions revealed a LTP-induced translocation of gamma PKC but not alpha/beta PKC into the cytosol in dentate gyrus but also in the other ipsilateral hippocampal regions. These data suggest different physiological roles of Ca(2+)-dependent PKC isoenzymes in activity dependent synaptic plasticity. PMID- 8003660 TI - Differential regulation of paired-pulse plasticity following LTP in the dentate gyrus. AB - The mechanisms underlying the expression of long-term synaptic potentiation (LTP) in the lateral and medial perforant path inputs to the dentate gyrus were examined in pentobarbital anaesthetized rats. Lateral path LTP was accompanied by a robust, long-lasting reduction in lateral path paired-pulse facilitation (PPF). The reduction in PPF lasted for at least 1 h, and remained even after post tetanic EPSP slopes were reduced to pre-tetanus levels. The induction of lateral path LTP and the corresponding reduction in PPF were blocked by the competitive NMDA receptor antagonist CPP. Medial path paired-pulse depression was not affected by medial path LTP. These data suggest that changes in transmitter release may contribute more to lateral path than to medial path LTP. PMID- 8003661 TI - Effects of cyclothiazide on synaptic responses in slices of adult and neonatal rat hippocampus. AB - The effects of cyclothiazide, a drug that blocks AMPA receptor desensitization, on synaptic responses were studied in field CA1 of hippocampal slices from adult and neonatal rats. Cyclothiazide (100 microM) reliably increased AMPA receptor mediated field EPSP decay times in adult slices but only after prolonged (60-120 min) applications. In neonatal slices, 30 min applications of cyclothiazide were sufficient to produce large and long-lasting increases in response decay times. Since the effects of cyclothiazide on AMPA receptor binding properties were similar in adult and neonatal forebrain membranes, the data indicate that the slow action of the drug in adult slices is probably due to diffusion barriers. The prolongation of EPSP decay by cyclothiazide suggests that AMPA receptor mediated synaptic responses in hippocampus are terminated by receptor desensitization. PMID- 8003662 TI - NGF increases [Ca2+]i in regenerating mature oligodendroglial cells. AB - The effect of NGF on [Ca2+]i of mature regenerating oligodendroglial cells was investigated by measuring fluo-3 fluorescence. NGF caused transient increases in [Ca2+]i, which could be inhibited by anti-NGF antibody. The rise in [CA2+]i was in part due to influx of extracellular Ca2+ since it was markedly attenuated in Ca2+-free solution. It also depended on release of Ca2+ from intracellular stores as tested by prior depletion with cyclopiazonic acid. These results support a role for Ca2+ in the effects of NGF on oligodendroglial cells. PMID- 8003663 TI - Astrocytes as rapid sensors of peripheral axotomy in the facial nucleus of rats. AB - Facial nerve transection leads to functional and structural reactions in lesioned motor neurones and surrounding glial cells. Data from this study provide evidence that the most rapid reaction described so far consists of an increase in immunoreactivity of connexin-43 (cx-43), the predominant gap junction protein in astrocytes. The ipsilateral facial nucleus is selectively marked as early as 0.75 to 1.5 hours after axotomy, while the unlesioned side as well as the unoperated controls remain faintly stained. Thus, enhanced coupling capacity of astrocytes by gap junctions appears to be a sensitive indicator of modified neuronal-glial interaction in the CNS. PMID- 8003664 TI - NMDA potentiates NGF-induced sprouting of septal cholinergic fibres. AB - Nerve growth factor (NGF) injected into the otherwise unlesioned adult rat septum induced sprouting of presumptive cholinergic fibres positive for p75NGFR and acetylcholinesterase (AChE). These fibres did not stain for tyrosine hydroxylase and therefore did not represent sympathetic ingrowth. Neurofilament staining on adjacent sections revealed fibres with similar morphology, suggesting new outgrowth in the form of sprouting rather than the upregulation of p75NGFR and AChE in pre-existing fibres. Simultaneous injections of subneurotoxic doses of N methyl-D-aspartate (NMDA) significantly potentiated the effect of NGF on cholinergic fibre sprouting and caused pronounced glial fibrillary acidic protein (GFAP)-positive astrocytosis. Application of NMDA alone did not elicit sprouting of this type. These findings indicate that NGF can induce the sprouting of uninjured adult rat septal cholinergic fibres in vivo and suggest that reactive astrocytes are not inhibitory to cholinergic axonal outgrowth, and might serve as a substrate for growing axons in the presence of NGF. PMID- 8003666 TI - The effect of chronic alcohol treatment on the radial maze performance of rats. AB - The effect of chronic alcohol drinking on maze behaviour was studied in laboratory rats. Thirteen animals received 20% alcohol for 15 weeks ad libitum, and 18 were kept under identical conditions drinking tap water. Both groups were then tested twice within one day for performance in an 8 arm radial maze after 48 h fluid deprivation. Reinforcing fluid droplets were placed at the end of each arm only at the beginning of the test. Total and erroneous entries to the arms, total time spent until reaching the criterion, and strategy of arm choice was recorded for each animal. Activity of the groups did not differ significantly, nor were differences in choosing strategy found. Alcoholic rats, however, showed a significant loss of performance in the second test: they frequently entered arms already visited, and in a number of cases were unable to complete the test within time. These and earlier findings suggest no impairment of learning ability or short term memory, but rather some kind of rigidity and invariability of behaviour. PMID- 8003665 TI - Protein kinase C suppresses receptor-mediated pial arteriolar relaxation in the diabetic rat. AB - Cerebral vasodilatory responses are selectively impaired in chronically hyperglycemic, diabetic rats. In this study, we tested the hypothesis that chronic hyperglycemia-induced protein kinase C (PKC) activation can account for the suppression of 2 separate receptor-mediated vascular relaxation processes: (1) endothelium-derived nitric oxide (NO) release, and (2) NO-independent beta adrenergic receptor (beta-AR) activation. The in vivo reactivity of pial arterioles was evaluated in anesthetized rats (streptozotocin-treated diabetics and controls) using a closed cranial window and intravital microscopy. Compared with controls, diabetic rats showed a substantial attenuation or loss of the arteriolar relaxation response accompanying suffusion of the receptor-linked, NO dependent agonists, acetylcholine (Ach) and adenosine diphosphate (ADP), and the beta-AR-agonist, isoproterenol (ISO). The vasodilatation induced by the direct NO donor, sodium nitroprusside (SNP), was the same in both groups. In the presence of the PKC inhibitor, staurosporine (STAURO), the Ach, ADP, and ISO responses were, largely restored and the SNP response was unaffected. STAURO produced no changes in Ach, ADP, ISO, or SNP responses in non-diabetic rats. These results suggest that PKC activation in chronically hyperglycemic, diabetic rats suppresses receptor-dependent NO release and desensitizes beta-ARs. PMID- 8003667 TI - Antiepileptic effects of NBQX against soman-induced seizures. AB - The ability of NBQX, a potent antagonist of AMPA glutamatergic receptors, to prevent or stop seizures induced by the organophosphate soman, an irreversible inhibitor of AChE, was studied in rats. NBQX administered concomitantly with soman prevents the onset of seizures (ED50: 29.2 mg kg-1, i.p.). Administered 5 min after the onset of seizures, NBQX greatly reduces the intensity of the epileptic activity. The same decrease of epileptic activity is observed, in the presence of atropine, when the administration of NBQX is delayed 15 min after the onset of seizures. NBQX thus appears as a promising antiepileptic candidate against soman-induced seizures. The roles of AMPA and muscarinic receptors in the onset and propagation of soman-induced epileptic activity are discussed. PMID- 8003669 TI - Asymmetrical changes in the choline acetyltransferase activity in the preoptic anterior hypothalamic area during the oestrous cycle of the rat. AB - There is evidence that the cholinergic system modulates, in a circadian and asymmetric way, the neural activity involved in the regulation of ovulation. In the present study we measured choline acetyltransferase (ChAT) activity during the oestrous cycle in both sides of the preoptic-anterior hypothalamic area (POA AHA) of the rat. The right side of POA-AHA showed significant changes in ChAT activity during the oestrous cycle. The activity of the enzyme was higher in the right side on the day of oestrous (47.3 +/- 3.2 nmol mg-1 protein 1 h-1 vs 25.8 +/- 2.4, p < 0.05), whilst on the second day of dioestrous the activity was higher in the left one (30.6 +/- 3.4 vs 20.0 +/- 1.5). The differences in the activity of ChAT observed support the idea of the existence of asymmetry in the POA-AHA cholinergic system which varies during the oestrous cycle. PMID- 8003668 TI - 6-Hydroxydopamine lesions reduce BDNF mRNA levels in adult rat brain substantia nigra. AB - Expression of brain-derived neurotrophic factor (BDNF) in the ventral mesencephalon has been assayed by mRNA in situ hybridization in adult rats with unilateral injections of 6-hydroxydopamine in the substantia nigra. On contralateral control sides, a specific hybridization signal was detected in the substantia nigra pars compacta (A9), ventral tegmental area (A10) and substantia nigra pars lateralis (A8). Cellular levels of BDNF mRNA were lower than those in BDNF expressing cortical and hippocampal neurons. The 6-hydroxydopamine injections completely abolished BDNF mRNA labeling in the pars compacta of the substantia nigra, whereas many labeled neurons remained in the ventral tegmental area and pars lateralis. The results strongly suggest that BDNF is expressed by nigral dopaminergic neurons. PMID- 8003670 TI - GABA uptake into isolated retinal Muller glial cells of the guinea-pig detected electrophysiologically. AB - In order to investigate GABA uptake into Muller glial cells electrophysiologically, we used the whole-cell voltage-clamp technique. Since Muller cells were insensitive to application of muscimol and baclofen, the expression of GABAA and GABAB receptors can be excluded. Therefore, the observed GABA current must be due to an electrogenic GABA transporter. This transporter is driven by the transmembrane Na+ gradient, as replacement of the extracellular Na+ by choline inhibits the GABA current. Currents evoked by cis-4-aminocrotonic acid, a GABAC specific agonist, are also inhibited by replacement of extracellular Na+, indicating that this compound is a substrate for the uptake. The competitive GABA uptake blockers beta-alanine and nipecotic acid are substrates of the transporter as well, and produce 42% and 65% of the currents elicited by the same GABA concentration, respectively. Affinity of the transporter for GABA is high, the Km value being 5 microM at -80 mV. PMID- 8003671 TI - Primary structure and functional expression of the AMPA/kainate receptor subunit 2 from human brain. AB - A full-length cDNA clone encoding the alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA)/kainate (KA) receptor subunit 2 (HBGR2) was isolated from a human brain cDNA library. The HBGR2 cDNA has an open reading frame of approximately 2.7 kb that codes for an 883-residue protein. At the amino acid level, HBGR2 is 98% identical to its rat counterpart GluR2, and 69% to the AMPA/KA receptor subunit 1 from human brain (HBGR1). Injection of cRNA transcripts from the HBGR2 into oocytes produces barely detectable kainate activated ionic currents, indicating that the HBGR2 subunit alone weakly expresses homomeric receptor channels. Coexpression of HBGR2 and HBGR1 transcripts, however, evokes kainate-dependent currents which activate at higher agonist concentration than those required by homomeric HBGR1 receptor channels. Coexpressed receptors display a linear current-to-voltage relationship at variance with the inwardly rectifying profile exhibited by HBGR1 homomers. Hence, the HBGR2 subunit coassembles with the HBGR1 subunit to form heteromeric receptor channels akin to the glutamate receptors from rodent brain. PMID- 8003672 TI - Mechanisms of Ca2+ mobilization in chick sensory neurones. AB - Mechanisms of Ca2+ mobilization from caffeine- and inositol-1,4,5-trisphosphate (IPA3)-sensitive internal Ca2+ stores were studied in embryonic chick sensory neurones. Caffeine transiently increased [Ca]i in one-quarter of all cells tested. For non-responsive cells caffeine elicited [Ca]i transients at elevated [Ca]i level indicating the operation of Ca(2+)-induced Ca2+ release. Injections of IP3 and GTP gamma S-induced [Ca]i transients but IP3-mobilizing agonists, carbachol and bradykinin, were either ineffective or produced weak responses. Pre treatment with staurosporine and H-7 increased both the peak [Ca]i and the percentage of cells responsive to agonists. The effects were abolished by phorbol esters indicating that down-modulation is mediated by protein kinase C. PMID- 8003673 TI - Use of a computerized brain atlas in magnetoencephalographic activation studies. AB - A pilot study was carried out to test the feasibility of an adjustable computerized brain atlas, adapted to the individual anatomy for localizing current dipoles by means of magnetoencephalography (MEG). The atlas can be adapted to individual computed tomography (CT) or magnetic resonance (MR) images. Position information is transferred between these imaging methods and MEG using a stereotactic technique. For this purpose, a special non-magnetic helmet was designed to be used together with the ordinary head fixation system. It seems likely that the proposed combination of the brain atlas with MEG, CT and MRI methods will become a powerful tool in exploring different brain functions. PMID- 8003674 TI - A hybrid frame of reference for visuo-manual coordination. AB - Visuo-kinesthetic matching of the orientation of an object in three-dimensional space has been studied by asking normal human subjects to align their unseen hand in parallel to the perceived orientation of a virtual stereoscopic object. Systematic errors were found for all three degrees of freedom of object orientation. These errors were much reduced when vision of the hand was allowed. The analysis of the distribution of the directional components of the errors revealed that matching performance without view of the hand was biased in a preferred direction that coincides with neither anatomical axes of the hand nor earth-fixed axes of visual space, but is intermediate between hand space and visual space. This suggests that a hybrid frame of reference is constructed by combining parallel multisensory information. PMID- 8003675 TI - Deficient cerebral activation pattern in stroke recovery. AB - Specific cerebral activations induced by unilateral tactile discrimination of macrogeometric objects were identified in positron emission tomography images of regional cerebral blood flow in patients recovered from hemiplegic stroke and in healthy volunteers. Primary sensorimotor cortex, supplementary motor area, superior parietal lobule contralateral to moving hand, and premotor cortex on both sides were regularly activated in normals contrary to patients showing consistent activations only in the primary sensorimotor cortex. Furthermore, areas of activations in parietal association, premotor and midfrontal cortical areas were far less consistently activated in patients than in healthy subjects. These results demonstrated in correspondence to the clinical observations that the patients had regained their ability to move the fingers of the affected hand but remained impaired in tactile discrimination. PMID- 8003676 TI - Activation of a bulbospinal opioidergic projection by pain stimuli in the awake rat. AB - We examined the expression of preproenkephalin mRNA in pain-modulating regions of the rat's brainstem using in situ hybridization histochemistry. We found that neurones in the Kolliker-Fuse nucleus, which receives projections from spinal nociceptive-specific cells, express enkephalin mRNA, that this expression is increased by noxious pinch applied to the skin of awake animals, and that these enkephalinergic neurones are part of a descending system that terminates in the rostroventral medulla and the spinal cord. These findings show that natural noxious stimuli activate opioidergic bulbospinal neurones that could directly modulate spinal nociceptive transmission. PMID- 8003678 TI - Rapid sensory remapping in the adult human brain as inferred from phantom breast perception. AB - We provide evidence for a perceptual marker of neuroplasticity in female mastectomy patients who reported phantom breast perceptions. When tactile stimuli were delivered to dorso-thoracic, shoulder and pinna regions ipsilateral to the mastectomy, these patients (in some cases even 5 days after the operation) referred the stimuli to the amputated breast mainly to the nipple. The somatosensory representation of the stimulated regions is probably adjacent to the former representation of the amputated breast. These results suggest that input from stimulated regions of the skin can drive neurones originally driven by input from the amputated breast. The apparent functional relation between pinna and nipple might give clues to the mechanisms underlying referred sensations and pain. PMID- 8003677 TI - Enhanced alpha-2 adrenergic controls and spinal morphine potency in inflammation. AB - The antinociceptive potency of spinal morphine is enhanced in rats after carrageenan-induced inflammation. This electrophysiological study examines whether changes in alpha-2 adrenergic systems are responsible. Dorsal horn nociceptive neurones were recorded under halothane anaesthesia in normal animals and animals with carrageenan inflammation. There was a mild increase in potency of the selective alpha-2 adrenoceptor agonist dexmedetomidine following carrageenan (ED50 = 1 microgram). Intrathecal idazoxan (100 micrograms), an alpha 2 antagonist, produced a significant facilitation of the C-fibre evoked response in carrageenan-treated but not normal animals. However since neither idazoxan (100 micrograms) or atipamezole (50 micrograms, another antagonist) influenced the potency of spinal morphine, the increased alpha-2 adrenergic activity in inflammation does not contribute to the enhanced potency of spinal morphine. PMID- 8003679 TI - Interlayer neurones in the rat superior colliculus: a tracer study using Dil/Di ASP. AB - Five different populations of interlayer neurones (ILNs) can be described after DiI/Di-ASP tracing in rat superior colliculus (SC). All of these labelled neurones preferentially lay in the rostro-medial part of the SC. Most of them are located in the stratum opticum and in the stratum griseum superficiale. Our results indicate that ILNs represent a minority of neurones in the superficial layers but may constitute a substantial population of neurones in the stratum opticum connecting the visual and the multimodal collicular layers. PMID- 8003680 TI - Combined blockade of NMDA and non-NMDA receptors produces respiratory arrest in the adult cat. AB - We studied the effects of the non-NMDA antagonist NBQX and of the NMDA antagonist dizocilpine (MK-801), administered separately or together, on the respiratory function of conscious cats. NBQX (20 mg kg-1) did not affect minute ventilation nor the timing of inspiratory and expiratory phases, but the addition of a small dose of dizocilpine (0.15 mg kg-1) induced inspiratory pauses and respiratory arrest in the inspiratory phase (apneusis). Similarly, larger doses of either NBQX or dizocilpine did not induce apneusis but the addition of a small dose of the other compound provoked an apneusis. Thus, a blockade of either non-NMDA or NMDA receptors is well tolerated, but the combined blockade of both receptor types severely disrupts the respiratory function in the cat. PMID- 8003682 TI - DNA damage consistent with apoptosis in transient focal ischaemic neocortex. AB - Transient focal ischaemia was produced in rat right neocortex by temporary middle cerebral artery occlusion. DNA damage was visualized in situ in cells of this right hemisphere but not in the contralateral hemisphere. The extracted damaged DNA exhibited laddered fragmentation which is indicative of apoptotic degradation. The amount of DNA damage was quantified by an end-labelling technique and shown to increase with the duration of the ischaemic insult. We conclude that the neurodegeneration resulting from focal ischaemia has an apoptotic component. PMID- 8003681 TI - APB (2-amino-4-phosphonobutyric acid) activates a chloride conductance in ganglion cells isolated from newt retina. AB - In vertebrate retinae, APB (2-amino-4-phosphonobutyrate) selectively activates glutamate receptors of ON-bipolar cells. Thus, APB has been used as a pharmacological tool for studying the functional retinal circuitry and the inputs to higher-order pathways of the visual centres. Direct action of APB on ganglion cells has not previously been demonstrated. We now report, using whole-cell patch clamp recordings, that APB has a direct inhibitory effect on ganglion cells isolated from newt retina. APB-induced currents were dependent upon the intracellular Cl- concentration. Their reversal potential values agreed with theoretical values of Cl- equilibrium potential. Strychnine, a glycine receptor blocker, inhibited the APB response. These results may suggest that APB activates the Cl- channels of ganglion cells through glycine receptors. PMID- 8003683 TI - Differential synaptic loss in the cortex in Alzheimer's disease: a study using archival material. AB - We have developed techniques to utilize immunocytochemical localization of synaptic protein (SNAP-25) in conjunction with image analysis to investigate synaptic loss in readily available archival material. Sections from 5 cortical regions were examined in cases of Alzheimer's disease (n = 7) and controls (n = 5). Image analysis was used to determine a relative synaptic index (RSI) and probe for changes in synaptic integrity. RSI value for cortical regions did not differ in controls. RSIs from sulci and gyri were significantly correlated in Brodmann areas 6, 9 and 18 (40 and 52 approached significance). Cases with Alzheimer's disease showed decreases in sulcal and gyral RSI values of between 60% (Brodmann area 6 < 0.01) and 10% (Brodmann area 18 > 0.4) and a lack of correlation in sulco-gyral values except in Brodmann area 18. We have demonstrated that synaptic pathology is heterogeneous with frontal cortex most and occipital cortex least affected. Sulci and gyri are affected to different degrees. The underlying cytoarchitecture of the cortex and its pattern of connectivity appears to have a considerable influence on the degree and extent of synaptic pathology. PMID- 8003684 TI - AMPA/KA receptor expression in radial glia. AB - The expression of four genes (GluR 1; 2; 3; 4) encoding functional subunits of the alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA)/low affinity kainate (KA) subtype of glutamate receptors was investigated in chick radial glia, namely Bergmann and Muller glial cells, using Northern blot analysis with oligonucleotide probes. Both cell types expressed the transcripts GluR 1; 3; 4, whereas the GluR 2 mRNA could not be detected. The synaptic localization of these receptors, their ion-channel properties and their regulation further strengthen the putative role of glial cells in the modulation of synaptic efficacy and plasticity. PMID- 8003686 TI - Frequency-specific blocking in the human brain caused by electromagnetic fields. AB - Based on preliminary observations that continuous exposure to electromagnetic fields (EMFs) produced an after-effect on human brain electrical activity, the effect of 10 Hz, 1 gauss, on the intrinsic activity of the brain at that frequency was studied. Ten subjects were exposed for 10 min and the 10 Hz spectral power was measured during the 1 min interval following stimulation and compared with control values obtained from the same subjects. Significantly reduced brain electrical activity from the occipital electrodes following termination of the EMF exposure was observed, thereby confirming the preliminary results. PMID- 8003685 TI - Expressed mu opiate receptor couples to adenylate cyclase and phosphatidyl inositol turnover. AB - The recently cloned rat mu opiate receptor cDNA has been expressed in COS and Chinese hamster ovary (CHO) cells to examine the coupling of this receptor to G protein linked second messenger systems and examine possible coupling to multiple second messenger systems. Morphine (1 microM) reduced both forskolin-stimulated cAMP levels and IP3 levels by 20 +/- 5 and 34 +/- 8% respectively in COS and CHO cell cultures expressing the cloned rat mu receptor cDNA. Both effects could be blocked by naloxone and Gpp(NH)p. These results represent the first clear representation of the second messenger system promiscuity possible with a single cloned opiate receptor. PMID- 8003687 TI - Response to acoustic stimuli increases in the ventral cochlear nucleus after stimulus pairing. AB - Recordings of activity in response to click and hiss were made from 364 units of the ventral cochlear nucleus of cats. The unit response to acoustic stimuli increased after forward or backward pairing of the stimuli with glabella tap and hypothalamic electrical stimulation. The results provide evidence against the widely held view that transmission through this initial brain stem relay of the auditory system is invariant, and suggest, instead, that the activity of the ventral cochlear nucleus changes to support increased attentiveness to acoustic signals after variably ordered pairing of conditioned and unconditioned stimuli. PMID- 8003688 TI - Electrolytic lesions to the optic chiasm affect circadian locomotor rhythms in lizards. AB - Electrolytic lesions to 85-95% of both optic nerves at the level of the optic chiasm (OC-X) induce a significant shortening of the free-running period (tau) of locomotor rhythms in Podarcis sicula held in constant temperature (29 degrees C) and constant darkness. Together with previous data in P. sicula, showing that retinalectomy (RET-X) in constant darkness also mostly induces a shortening of tau, the present results demonstrate that the retinae play a central role in the control of behavioural circadian rhythmicity independently of light perception. The fact that OC-X and RET-X affect locomotor rhythms in the same way (mostly by shortening tau), strongly supports the contention that the influence of the retinae on the circadian system is neurally mediated. PMID- 8003689 TI - Decrease of complexity in EEG as a symptom of depression. AB - Nonlinear dynamic analysis provides new methods for the processing of the electroencephalogram (EEG). We demonstrate here that the EEG dynamics of major depressive subjects is more predictable, that is less complex, than that of control subjects. Moreover, the consequence of treatment upon the EEG dynamics seems to be dependent on the appearance of the illness. Although the specificity of this dynamic signature for different stages of depression is to be confirmed, the assumption of a strong link between a healthy system and a high level of complexity in dynamics is further supported. PMID- 8003690 TI - TGA3 is a distinct member of the TGA family of bZIP transcription factors in Arabidopsis thaliana. AB - TGA1a is a well-characterized transcription factor that may mediate the root specific and auxin-responsive expression of some plant genes. In tobacco, Southern blot and genomic cloning analyses have shown that TGA1a consists of at least four closely related genes. Since TGA1a belongs to the bZIP class of transcriptional factors, the protein products of the tobacco TGA1a family are likely to form hetero-dimers with each other in addition to the homo-dimers. In order to find a model plant system that may have less genomic complexity, we have now characterized a TGA1a-related gene (TGA3) from Arabidopsis thaliana. Southern blot analyses at high stringency suggest that Arabidopsis contains only one copy of TGA3 per haploid genome. However, low stringency Southern blot analyses with homologous and heterologous probes suggest that there is a multigene family of TGA1a-related genes present in Arabidopsis, of which TGA1, TGA2 and TGA3 are members. Although these gene members share a highly conserved bZIP region, they are not genes with high homologies at the nucleotide level. Similar to TGA1a of tobacco, TGA3 is most highly expressed in root tissues and recombinant TGA3 protein shows similar DNA-binding site specificity to that of TGA1a in vitro. Comparison of the genomic organization between TGA3 and the tobacco homologue PG13 reveals striking conservation in the sizes and positions of exons and introns in the region surrounding the bZIP domain. PMID- 8003691 TI - Characterization and in situ localization of a salt-induced tomato peroxidase mRNA. AB - NaCl treatment of tomato plants in hydroponic culture at concentrations as low as 50 mM resulted in enhanced accumulation of transcripts of TPX1, a full-length cDNA clone that we had isolated from a library of NaCl-treated tomato plants using a peroxidase-specific oligonucleotide probe. Although the overall amino acid sequence identity of TPX1 to other peroxidase genes was less than 45%, there was a very high degree of identity in all of the conserved domains. The deduced amino acid sequence included the presence of a N-terminal signal peptide but not the C-terminal extension present in peroxidases targeted to the vacuole. The mature protein has a theoretical pI value of 7.5. Transcripts that hybridized to TPX1 were detected only in the roots with higher levels of mRNA in epidermal and subepidermal cell layers. Isoelectric focusing of root extracts showed two major bands of peroxidase activity at pI 5.9 and 6.2. Both activities increased with salt treatment. Southern analysis indicated the presence of only a single TPX1 gene in tomato. PMID- 8003693 TI - Chloroplast encoded thioredoxin genes in the red algae Porphyra yezoensis and Griffithsia pacifica: evolutionary implications. AB - A gene encoding a thioredoxin protein was identified in the chloroplast genome of the rhodophyte Porphyra yezoensis. The P. yezoensis trxA gene contains 324 bp and is transcribed into a 0.7 kb messenger RNA. Analysis of the transcription start site demonstrates that canonical chloroplast -10 and -35 sequences are not present. The deduced amino acid sequence of the thioredoxin gene from the red algae has the greatest similarity to type m thioredoxins, providing strong support for the hypothesis that type m thioredoxins in photosynthetic eukaryotes originated from an engulfed bacterial endosymbiont. Hybridization analysis of nuclear and chloroplast DNAs from several members of the phyla Chromophyta and Rhodophyta using P. yezoensis DNA as a probe demonstrated strong hybridization to the chloroplast and nuclear genomes of Griffithsia pacifica and a weak cross hybridization to the chromophyte P. foliaceum. The G. pacifica chloroplast gene has a 66% identity with the P. yezoensis DNA, contains conserved active site amino acid residues, but lacks a methionine start codon. PMID- 8003692 TI - Initiator-dependent transcription in vitro by a wheat germ chromatin extract. AB - The development of plant in vitro transcription systems transcribing faithfully and efficiently from a broad range of plant nuclear promoters has remained a challenge. We examined the nucleotide sequence requirements for faithful and efficient transcription in a wheat germ chromatin extract (Yamazaki et al., Plant Mol Biol Rep 8: 114-123). The wheat germ chromatin extract was tested with a series of chimeric promoter constructs containing plant promoter sequences upstream from the TATA box, TATA boxes, and cap-site sequences (from -10 to +14, relative to the major in vivo initiation site) in different combinations. The plant extract transcribed faithfully from several chimeric promoters containing the capsite sequence of the parsley chalcone synthase promoter. The transcription was sensitive to the RNA polymerase II-specific inhibitor alpha-amanitin and was only dependent on the chalcone synthase cap-site sequence which therefore fulfils the operational criteria for a plant initiator element. Mutations of the putative chalcone synthase initiator element defined a core sequence '5'TAACAAC' around the initiation site that was necessary for efficient transcription in vitro. In contrast to the extract, purified wheat germ RNA polymerase II showed no preference for transcription from the major chalcone synthase in vivo initiation site. PMID- 8003695 TI - Expression and genomic organization of a dinoflagellate gene family. AB - The luciferin-binding protein (LBP) of the dinoflagellate Gonyaulax polyedra is encoded by a large gene family with at least two different members. To more fully understand the expression and genomic organization of this gene family, 40 full length LBP cDNAs were isolated and mapped with the restriction enzymes Xho I, Eco RI, Pvu II and Hind III. All cDNAs isolated could be placed into one of two groups called LBP alpha and LBP beta. Two LBP alpha group cDNAs were completely sequenced and were found to share 99% identity at both the nucleotide and protein levels. One LBP beta cDNA was sequenced and was found to share only 86% sequence identity with the LBP alpha group at both the nucleotide and protein levels. Both groups of message appear to be expressed at nearly equal levels since (1) two dimensional gels of purified LBP show two protein isoforms present in roughly equal amounts and (2) northern blots using group-specific probes suggest that cellular levels of LBP alpha and LBP beta mRNAs are identical. Genomic Southern blots using group-specific probes suggests that the copy number of both gene groups is very similar and that LBP gene loci are organized as tandem repeats of either LBP alpha or LBP beta sequences. PMID- 8003694 TI - The legumin gene family: a reconstructed Vicia faba legumin gene encoding a high molecular-weight subunit is related to type B genes. AB - Nucleotide sequence information from a partial genomic clone, a cDNA clone, a RACE clone and a PCR fragment was combined to reconstruct the first reported complete gene sequence encoding a large legumin subunit, designated LelB3. The length difference to the well-characterized major legumin subunits is caused by an extended glutamine/glutamic acid-rich region encoded by the C-terminal part of the alpha chain. Amino acid sequence comparisons reveal that gene LelB3 is more closely related to B-type than to A-type legumin genes of Vicia faba. Gene LelB3 is a member of a small gene family as indicated by published (Pich and Schubert, Biol Zbl 112 (1993); 342-350) and limited own data. PMID- 8003696 TI - The highly edited orf206 in Oenothera mitochondria may encode a component of a heme transporter involved in cytochrome c biogenesis. AB - A highly transcribed region in Oenothera mitochondria codes for a reading frame (orf206) which shows high homology to the Marchantia encoded mitochondrial open reading frame orf277 and is also conserved in the mitochondrial genomes of Arabidopsis thaliana and Daucus carota. Transcripts of orf206 are modified by cytidine to uridine changes in 46 positions by RNA editing, affecting 30% of all cytidines and 15% of the total encoded amino acids. This ORF is cotranscribed with an upstream reading frame and with the downstream rps 14 gene. The orf206 deduced protein shows high similarity to polypeptides which are proposed to be part of an ABC-type heme transporter involved in cytochrome c biogenesis in Bradyrhizobium and Rhodobacter. PMID- 8003697 TI - Molecular cloning, sequence determination and heterologous expression of nucleoside diphosphate kinase from Pisum sativum. AB - Protein sequence data derived from the N-terminal region of a 17 kDa polypeptide associated with the microsomal membrane fraction from Pisum sativum was used to design degenerate oligonucleotides which were used to amplify P. sativum cDNA via the polymerase chain reaction (PCR). Amplified cDNA was used as a probe to screen a P. sativum cDNA library and a cDNA clone, NDK-P1 was isolated and sequenced. The protein encoded by NDK-P1 had a calculated molecular mass of 16,485 Da and possessed substantial homology with nucleoside diphosphate kinases (NDKs) isolated and cloned from other sources. High levels of expression of NDK-P1 protein were achieved in Escherichia coli using a T7-driven expression system. Recombinant NDK-P1 protein was shown to possess NDK activity and had similar biochemical characteristics to NDKs isolated from other sources. The Michaelis constants for a variety of nucleoside diphosphate (NDP) substrates were found to be broadly similar to those reported for other NDKs, with thymidine nucleotides being the substrates of greatest affinity. PMID- 8003698 TI - Separation of two classes of plastid DNA-dependent RNA polymerases that are differentially expressed in mustard (Sinapis alba L.) seedlings. AB - Chloroplast and etioplast in vitro transcription systems from mustard have different functional properties, which is reflected in differences in phosphorylation status. Here we report another transcription control mechanism, which involves two plastid DNA-dependent RNA polymerases designated as peak A and peak B enzymes. Both are large multi-subunit complexes, but differ in their native molecular mass (> 700 kDa for peak A and ca. 420 kDa for peak B) and in their polypeptide composition. The A enzyme is composed of at least 13 polypeptides, while the B enzyme contains only four putative subunits. Peak B activity is inhibited by rifampicin, whereas that of peak A is resistant. RNA polymerase activity was compared for plastids from cotyledons of 4-day-old seedlings that were grown either under continuous light (chloroplasts) or in darkness (etioplasts), or were first dark-grown and then transferred to light for 16 h ('intermediate-type' plastids). While the total activity was approximately the same in all three cases, enzyme B was the predominant activity obtained from etioplasts and enzyme A that obtained from chloroplasts. Both had equal activity in preparations from the 'intermediate-type' plastid form. Both activation/inactivation and differential gene expression seem to play a role in the regulation of the plastid transcription machinery. PMID- 8003699 TI - Oncogene arrangement in a shooty strain of Agrobacterium tumefaciens. AB - The Agrobacterium tumefaciens nopaline strain 82.139 induces non-teratogenic shooty tumours on several plant species. We have determined the position of the T region oncogenes in a 11.4 kb Xba I fragment which shows a general organization similar to its pTiC58 counterpart. Sequence analysis of the 4.7 kb right part of this fragment allowed us to identify the pTi82.139 ipt, 6b and nos coding sequences. pTi82.139 lacks the 6a gene, which lies between the ipt and 6b genes in pTiC58. The intervening region between the 6b and the nos genes contains an additional ORF with homology to ORF 21 (transcript 3') from the TR-DNA of octopine strain pTi15955. PMID- 8003700 TI - Differential screening of mitochondrial cDNA libraries from male-fertile and cytoplasmic male-sterile sugar-beet reveals genome rearrangements at atp6 and atpA loci. AB - As part of a strategy to define differences in genome organization and expression between cytoplasmic male-sterile (CMS) and male-fertile (MF) sugar-beet mitochondria, cDNA libraries from both mitochondrial genotypes were constructed. Preliminary screening with ribosomal RNA gene probes identified candidate cDNA clones corresponding to structural genes. In addition, reciprocal hybridization experiments were performed using labelled first-strand cDNA to identify uniquely transcribed sequences. One cDNA clone (pYC700) is unique to CMS mitochondria and is located upstream of the F0F1-ATPase subunit 6 gene (atp6). Another cDNA clone (pYC130), when used as a probe in northern hybridization analysis, revealed novel transcript profiles in CMS sugar-beet mitochondria. Sequence analysis of this cDNA showed strong homology with the F0F1-ATPase subunit alpha (atpA) coding sequences from several higher plants. The atp6 and atpA loci from each genotype were cloned and the genomic organization, DNA sequence and transcription of each locus was studied. Differences in the transcript profiles of each gene are a consequence of genomic rearrangements 5' to the coding sequence. PMID- 8003701 TI - Deregulated production of interleukin-8 (IL-8) in autoimmune thyroid disease studied by newly developed IL-8 radioimmunoassay. AB - We have developed a sensitive, reproducible and specific radioimmunoassay for human interleukin-8 (IL-8). Using 125I-labelled IL-8 and polyclonal rabbit antisera raised against recombinant human IL-8, a competitive inhibition assay was developed which could detect 5 pg/ml of human IL-8. Other interleukins, growth factors, hormones, peptides and lectins did not affect the assay. IL-8 measured in supernatants of culture media of stimulated human peripheral blood mononuclear cells (PBMC). Kinetics of IL-8 production in SAC-stimulated PBMC from seven normal subjects revealed that the production of IL-8 was detectable within 12 h and reached a plateau at 24 h. IL-8 levels in SAC-stimulation of PBMC from untreated patients with autoimmune thyroid diseases (Graves' disease and chronic thyroiditis) were significantly higher than in normal controls. However, after treatment, IL-8 production decreased to normal. The present study demonstrates the usefulness of quantitating human IL-8 produced by PBMC and the presence of a deregulated production of IL-8 in autoimmune thyroid diseases. PMID- 8003702 TI - Effect of space flight on the development of endocrine functions in rats. AB - The effects of the exposure to space flights on plasma hormone levels were studied in adult male rats, in pregnant females and in their progeny. An increase of plasma corticosterone (CS) and insulin (I) levels was found in male rats after space flights for a period of 7, 15, 18 and 20 days. Plasma levels of growth hormone (GH) were decreased and those of epinephrine (E) and norepinephrine (NE) were elevated in rats exposed to longer space flights (18 or 20 days). In pregnant female rats no significant changes of plasma concentrations of CS, GH, I, E and NE were noted after short term space flight (5 days). However, the plasma prolactin levels were elevated. In young animals exposed to space flight during fetal development no changes of plasma I and prolactin levels were noted during the period of postnatal growth. However, the plasma CS levels were elevated in these rats and no gradual increase of CS plasma concentration was observed during the postnatal period. The plasma GH levels were reduced in rats exposed to space flight and the levels of catecholamines in plasma and in adrenal glands were elevated in 30 and 100 day old rats exposed to microgravity during the fetal development. These results demonstrated: 1. that exposure of rats to space flight is followed by changes in I and CS plasma levels, but the sympathetic-adrenomedullary system is only slightly activated by longer space flights; 2. that a short term space flight is only a mild stressor for pregnant rats and slightly affects the activity of adrenocortical and sympathetic adrenomedullary systems during the development of their offsprings. PMID- 8003703 TI - A case of inappropriate non-neoplastic secretion of TSH treated with bromocriptine. AB - A 67 year old patient with overt signs of hyperthyroidism had high serum TSH values in addition to high T3 and T4 values. Initial treatment with propyltiouracil (PTU) reduced the high serum thyroid hormone levels but TSH levels were further increased. With an augmented TSH response to TRH and negative sella tomography, diagnosis of inappropriate secretion of TSH was made. PTU was stopped and bromocriptine 10 mg daily given with perfect result in 18 weeks. The patient is euthyroid on bromocriptine therapy. PMID- 8003704 TI - Cross-linking of iodinated prolactin to rat liver nuclear protein. AB - The specific binding of prolactin (PRL) in rat liver nuclei have been examined. Following cross-linking with the use of 125I-rat prolactin and autoradiography the evidence is presented for the specific binding of PRL to a nuclear protein with low Mr of about 7000. This study shows that the PRL binder in rat liver nuclei is a small protein and probably differs from molecular form of the rat liver membrane prolactin receptor. PMID- 8003705 TI - Thyrotropin-releasing hormone (TRH) inhibits vasopressin release from hypothalamo neurohypophysial system of rats drinking hypertonic saline. AB - Rats drinking ad libitum tap water or hypertonic (i.e. 2%) sodium chloride solution were given intracerebroventricularly (i.c.v.) for three days, thyrotropin-releasing hormone (TRH) in a daily dose of 200 ng dissolved in 10 microliters of 0.9% sodium chloride. Treatment with TRH resulted in significantly increased hypothalamic vasopressin content in both euhydrated (i.e. given tap water ad libitum) and salt-loaded rats. In rats given hypertonic saline, neurohypophysial vasopressin content increased. Plasma vasopressin concentration was distinctly diminished under TRH treatment, the respective difference being significant, however, barely in salt-loaded rats. The present data suggest that TRH may be involved in some regulatory processes related to vasopressin biosynthesis and release from the rat hypothalamo-neurohypophysial system. PMID- 8003706 TI - Carnitine, fat metabolism and hormones. PMID- 8003707 TI - Serum thyroglobulin level and thyrotropin receptors in plasma membranes from thyroid nodular relapse. AB - The parameters of 125I-bTSH binding to plasma membrane as well as serum thyroglobulin (Tg) level in 13 euthyroid females, suffering from scintigraphically functioning thyroid nodule, were investigated. Thyroid tissue samples of five euthyroid patients were obtained by surgical reintervention, which was done because of scintigraphically functioning nodular goitre relapse (Group 1). Data were compared with two control groups. One of them (Group 2) consisted of 5 euthyroid females in whom partial thyroidectomy was done because of solid functioning thyroid nodule. Long-term follow-up during postoperative period confirmed normal morphofunctional status in them. The second control (Group 3) is consisted of 3 patients suffering from goitre relapse now. The percent of specific 125I-bTSH binding and the affinity of its binding to plasma membranes from nodular goitre relapse were lower (2.05% +/- 0.82; Kd1: 0.56 +/- 0.34 10(-9) M; mean and S.D., resp.) than to the membranes obtained from surrounding perinodular tissue (0.32 +/- 0.89; Kd1: 0.20 +/- 0.77 10(-9) M, resp.). However, the level of high affinity TSH receptors in plasma membranes prepared from nodular goitre relapse was higher than that in perinodular, assumed to be normal tissue (11.21 +/- 0.87 fmol/mg prot. versus 6.29 +/- 2.24 fmol/mg prot., mean and S.D.). Plasma membranes obtained from goitre relapse were characterised by high total number of receptor and binding sites (N1 + N2) for TSH. In Group 1 and 3 elevated serum Tg levels were confirmed during follow-up period with no correlation with TSH, which characterises a normal physiological status of regulation. PMID- 8003708 TI - Epitestosterone--a hormone or not. AB - Epitestosterone is a natural component of biological fluids of several mammals including man. For a long time it has been believed that it is a metabolite without any hormonal activity and without any marked relationship to the hormonal state in health and disease. The biosynthetic pathway as well as the site of its formation in man has not been unequivocally confirmed until now. It apparently parallels the formation of testosterone but, on the other hand, its concentration is not influenced by exogenously administered testosterone. This fact creates the basis of the present doping control of testosterone abuse. In 1989 an observation was presented in a dermatological study that epitestosterone has an effect counteracting the action of testosterone on flank organ of Syrian hamster. Further studies showed that a complex action consisting of competitive binding of epitestosterone to androgen receptor, of inhibition of testosterone biosynthesis and its reduction to dihydrotestosterone and of antigonadotropic activity could be demonstrated in rat, mice and human tissues. It can be presumed that epitestosterone as a natural hormone can contribute to the regulation of androgen dependent events as e.g. to the control of growth of prostate or body hair distribution. PMID- 8003709 TI - Effects of dexamethasone on TRH, TRH-glycine and pre-pro-TRH (178-199) levels in various rat organs. AB - The effect of dexamethasone administration on the concentration of thyrotropin releasing hormone (TRH) and pre-pro-TRH connecting peptides TRH-glycine (TRH Gly), and pre-pro-TRH (178-199) in various rat organs was studied. Three groups of 35 rats each were injected dexamethasone (Group A: 25 micrograms/100 g; Group B: 500 micrograms/100 g) or saline (Group C: control). The subgroups of 7 rats each were decapitated at 1, 2, 3, 4 and 24 h after the injection and the levels of TRH-Gly, pre-pro-TRH (178-199) and TRH in the hypothalamus, cerebrum, cerebellum and brain stem, stomach, retina were estimated by specific radioimmunoassays. The level of TRH-Gly and pre-pro-TRH (178-199) in the hypothalamus decreased significantly in groups A and B at 1-4 hours after the injection, and then returned to pretreatment levels at 24 h after the injection. In contrast, TRH levels in the hypothalamus increased significantly in groups A and B at 1-4 h after the injection. The TRH-Gly, pre-pro-TRH (178-199) and TRH levels in other organs showed no changes after dexamethasone injection. From these findings it is concluded that dexamethasone inhibits the synthesis and secretion of TRH and the maturation of pro-TRH in the hypothalamus, while its effects on other organs is different from the hypothalamus. PMID- 8003710 TI - Interrelations between body weight, cigarette smoking and spine mineral density in osteoporotic Czech women. AB - This study was designed to assess the influence of body weight and cigarette smoking on vertebral bone mineral density in 241 osteoporotic and age matched 98 normal Czech women. The present study demonstrated that bone density and the frequency of atraumatic vertebral fractures was not related to the body weight. High body weight was not found to show any protective action on bone. However, among a group with vertebral fractures, bone mineral density in cigarette smokers was significantly lower than in nonsmokers, but this effect was not associated with low body weight. The osteoporotic women with and without vertebral fractures had high serum cholesterol concentration which is unequivocally associated with peripheral vascular disease. Thus, our results are suggesting the relationship between atherosclerosis and osteoporosis. PMID- 8003711 TI - Acute effect of some hormones on the metabolism of polyamines in rat liver in vivo as measured by their biliary excretion. AB - Groups of 6-11 adult male rats were anesthetized with pentobarbital and thin polyethylene tubings were inserted into the common bile duct and femoral vein. The bile was collected for 1 or 2 h periods within a total of 6-8 h and the excretion of putrescine (PUT), spermidine (SPD) and histamine (HA) was estimated with the aid of high performance liquid chromatography and expressed as nmol per time. In each experiment the first time interval was used as control one and then various hormones (insulin, glucagon, cholecystokinin and dexamethasone) and glucose were infused into a femoral vein. Significant increase of PUT and HA excretion was found after glucose infusion which was prevented by simultaneous infusion of insulin. Moreover, the infusion of cholecystokinin resulted in a similar significant increase of PUT, SPD and HA, while dexamethasone and glucagon were without any considerable effect. Finally, a significant increase in PUT and SPD excretion was observed after severe hypoglycemia due to the infusion of insulin. It is concluded that such approach may be used as a novel method for a study of polyamine metabolism in the liver in vivo. PMID- 8003712 TI - Evaluation of SHBG test for disclosure of insensitivity to androgens. AB - A laboratory test enabling to reveal and confirm the suspicion on the insensitivity to androgens was evaluated. The test consisted of determination of the decline in plasma level of sex hormone binding globulin (SHBG) on the 7th day after administration of a single dose of testosterone preparation (Testoviron Depot 100, Schering, 2 mg/kg body weight). The upper limit of percentual SHBG decline, below which the patients can be considered normal responders (i.e. subjects without insensitivity to androgens), obtained from the follow up of the time course of SHBG changes after Testoviron application to 6 healthy men, was established as 83.6%. The level of percentual SHBG decline, above which the patients were considered non-responders with impaired peripheral sensitivity to androgens was assessed from the imprecision of immunoradiometric determination of SHBG and amounted 91.9%. The test was used and evaluated in 26 patients with 46 XY karyotype, representing various cases of intersex, gonadal dysgenesis and male hypogonadism, out of which four subjects with clinically confirmed impaired peripheral sensitivity to androgens were discovered. The test however, appeared not to be reliable in cases of very low basal SHBG levels, i.e. below 15 nmol/l. PMID- 8003713 TI - Epidermal growth factor and prolactin in rat anterior pituitary after chronic treatment with estradiol and triiodothyronine. AB - Adult male rats were treated for 20 days either with estradiol benzoate (EB; 10 mg/kg twice a week i.m.) or triiodothyronine (T3; approx. 500 micrograms/kg daily mixed to the food) or both and the concentration of epidermal growth factor (EGF) and prolactin (PRL) in the anterior pituitary (AP) was estimated. In a preliminary experiment no difference in EGF content in the AP of male and female rats was found. The administration of EB was followed by highly significant increase in AP weight and a significant decrease in EGF content per mg of the AP, but not per whole AP. The concentration of rPRL was significantly increased in AP and serum of EB treated animals. After T3 treatment the mean concentration of EGF in the AP was slightly elevated as compared with controls. The administration of T3 together with EB prevented the increase of AP weight as observed after EB alone. However, the content of EGF as expressed per mg of the AP was not different from that in control group, though it was elevated when expressed per whole gland. PMID- 8003714 TI - Studies on the immunomodulatory effects of vitamin D. AB - The effect of vitamin D on T lymphocytes was investigated using the test of active E-rosettes formation. It was found that: 1. A single oral administration of 600,000 IU of vitamin D2 causes a significant increase in the formation of active E-rosettes. The peak of the increase was found 24 hours after the administration of vitamin D. The formation of E-rosettes the seventh day of the study was comparable with the pre-administration value; 2. Sera with higher concentration of 1,25-dihydroxyvitamin D[1,25(OH)2D] cause a significant increase in the formation of active E-rosettes; 3. Vitamin D is capable of reverting significantly the effect of a serum factor which suppresses the active E-rosettes formation. The authors observed a significant decrease in the effect of trypsin on the lymphocytes after oral administration of a single oral dose of 600,000 IU of vitamin D2. The trypsin-treated lymphocytes regained their lost capacity to bind sheep red blood cells (SRBC) when incubated with AB serum at 37 degrees C for 3 hours. The recovery of E-rosettes-forming capacity of trypsinised lymphocytes considerably increased when the cells were incubated with serum containing higher concentration of 1,25(OH)2D of 600,000 IU of vitamin D2. PMID- 8003715 TI - Plasma endothelin 1/2 levels in healthy blood donors and in hypertensive patients: clinical application. AB - Normal endothelin 1/2 levels and their correlation with age were evaluated and compared with endothelin 1/2 levels in hypertensive patients. Plasma endothelin 1/2 (ET) levels were measured in healthy blood donors, mostly males, of mean age 36 +/- 8 years (36 subjects), subdivided into three groups: 17-30, 31-40 and above 40 years of age (41-59 yrs). Hypertensive patients (15 subjects) were subdivided into two groups: essential and nephrogenic hypertension. The normal ET levels in the three age groups (means +/- S.D.) were: 0.58 +/- 0.19, 0.62 +/- 0.31, and 0.80 +/- 0.28 fmol/ml, respectively. The average ET level for the whole normal population was 0.66 +/- 0.28 fmol/ml. Only the differences between the mean ET levels in the first and last group were significant (P < 0.05). The difference between the mean ET levels in smokers 0.71 +/- 0.28 fmol/ml (53% of total population) and non-smokers 0.65 +/- 0.28 fmol/ml, women and men, irrespective of age, was not found to be significant. The average ET level in all patients with hypertension (0.91 +/- 0.37 fmol/ml) was significantly higher than the average ET level in blood donors of the same age group (P < 0.05). Although patients with essential hypertension had elevated ET levels compared with control, the difference between the mean ET level in these patients (0.77 +/- 0.24 fmol/ml) and in the corresponsding control group (0.62 +/- 0.31 fmol/ml) was not significant.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8003716 TI - When abstract moralizing runs amok. PMID- 8003717 TI - The skilled specialist's ethical duty to treat. PMID- 8003718 TI - Ethics committees and family ghosts: case studies. PMID- 8003719 TI - Do formal advance directives affect resuscitation decisions and the use of resources for seriously ill patients? SUPPORT Investigators. Study to Understand Prognoses and Preferences for Outcomes and Risks of Treatments. PMID- 8003720 TI - Clinical dilemmas when patients want assistance in dying. PMID- 8003721 TI - Nurses' perspectives on implementation of the Patient Self-Determination Act. PMID- 8003722 TI - Neuromuscular paralysis and withdrawal of mechanical ventilation. PMID- 8003723 TI - The physician's duty to treat in emergencies: accepting patients in transfer. PMID- 8003724 TI - Commentary on "The skilled specialist's ethical duty to treat". PMID- 8003725 TI - Ethics consultation is not therapy. PMID- 8003726 TI - First-person plural: community and method in ethics consultation. PMID- 8003727 TI - Confronting the "near irrelevance" of advance directives. PMID- 8003728 TI - Advance directives: what is it reasonable to expect from them? PMID- 8003729 TI - Outcomes research and advance directives. PMID- 8003731 TI - Gallstone pancreatitis: mechanisms and management. PMID- 8003730 TI - Biliary scintigraphy in the diagnosis of acute cholecystitis: a review of 100 cases. PMID- 8003732 TI - Endoscopic therapy of acute and chronic pancreatitis. PMID- 8003733 TI - Activity reduction and disability among persons with diabetes. PMID- 8003734 TI - Images and patterns in medicine. Gallstone ileus. PMID- 8003736 TI - A meeting of minds. PMID- 8003735 TI - The realities of pancreatic disease. PMID- 8003737 TI - Aetiology and pathogenesis of chronic inflammatory bowel disease. AB - While Crohn's disease and ulcerative colitis are both conditions characterized by intestinal inflammation, with some overlap in their clinical and histological features, they are essentially different in pathogenesis. Crohn's disease appears to be primarily a condition of chronic T-lymphocyte activation, with tissue damage induced by secondary macrophage activation. What activates the T-cells is unknown. In this chapter we look at the evidence for and against cell-wall deficient mycobacteria species, viral infection of vascular endothelium and luminal contents as potential mechanisms of chronic activation. In ulcerative colitis, by contrast, there is no strong evidence for T-cell activation, and humoral mechanisms predominate. While the finding of atypical anti-neutrophil cytoplasmic antibodies (P-ANCAs) may be useful in screening, the only novel pathogenetic discovery is the co-localization of a 40 kD colonic autoantibody with immunoglobulins and complement on the apical enterocyte surface. Despite the fundamental differences in initiating mechanisms, the two conditions have many 'downstream' inflammatory processes in common. We discuss the evidence for local production of cytokines, arachidonic acid metabolites and reactive oxygen and nitrogen radicals, highlighting the potential adverse consequences for intestinal vascular integrity. PMID- 8003738 TI - Radiological investigation of chronic inflammatory bowel disease in childhood. AB - The radiological investigations relevant to chronic IBD are described briefly with emphasis placed on compression techniques in small bowel studies. A classification for reporting small bowel Crohn's disease is proposed, where the disease is staged as early, advanced or complicated, and the extent of involvement measured directly from the film. The terminal ileum may be normal in 20% of children with proximal Crohn's disease, so that ileoscopy should not be used to exclude small bowel disease. Radiological assessment of the small bowel is important in management. Surgical referral was based on the radiological changes in 6% of patients, and in 24% the presence of extensive uncomplicated small bowel Crohn's disease led to treatment with elemental diet. The use of some specialized examinations, such as the instant and ileostomy enema, are discussed. PMID- 8003739 TI - Endoscopic features of chronic inflammatory bowel disease in childhood. AB - Flexible endoscopy, performed after oral bowel preparation and under moderate intravenous sedation, proves to be well tolerated, safe and highly effective in the diagnosis and management of children with IBD. At St Bartholomew's Hospital it is performed as the investigation of first choice, on the basis that it supplies colour documentation, histopathological and (where relevant) bacteriological evidence, which achieves certain confirmation or exclusion in almost every case and in the shortest possible time. Biopsies must always be taken, as mucosa of normal appearance can show either microscopic ulcerative colitis or Crohn's disease. When there are the characteristic 'aphthoid' ulcers, visual diagnosis of Crohn's disease is reasonably certain, particularly in early stage disease, although amoebic and other infective causes of colitis can give misleadingly similar appearances. The endoscopist can usually inspect (and almost always biopsy) the terminal ileum, and can expect many children to show the prominent 'nodular lymphoid hyperplasia' which is essentially a normal finding though sometimes misdiagnosed radiologically as being Crohn's deformity. However, it is important that radiological assessment by barium follow-through complements colonoscopy in view of the not infrequent cases of intestinal Crohn's disease in children where the proximal small intestine is involved, even if the colon and terminal ileum are spared. PMID- 8003740 TI - Medical management of chronic inflammatory bowel disease. AB - In the absence of a definitive cure for Crohn's disease and ulcerative colitis, the aim of therapy must be to induce and maintain clinical remission at acceptable cost to the patient in terms of adverse effects. Despite the differences in their pathogenesis, the first-line treatments for Crohn's disease and ulcerative colitis are still based upon combinations of amino-salicylic acid derivatives and corticosteroids, although the use of enteral nutrition regimes is becoming increasingly widespread in Crohn's disease. In this chapter we attempt to provide reasonably didactic guidance for the management of most cases of chronic inflammatory bowel disease. However, we have tried to go beyond this brief, motivated by the recent explosion in knowledge of inflammatory mechanisms, to suggest a rational approach to the choice of newer and less well tested therapeutic approaches in the affected child who is not responding effectively. The relative failure of cyclosporine therapy in Crohn's disease has been particularly disappointing in view of its ideal theoretical suitability. However, the encouraging early reports of treatment with anti-CD4 and anti-TNF alpha monoclonals suggest that the shift from broad spectrum immunomodulation to the targeting of critical components of the inflammatory cascade may yet field important dividends. PMID- 8003741 TI - Surgical therapy of chronic inflammatory bowel disease in childhood. AB - The overall impression gained from the experience of the Departments of Paediatric Gastroenterology and Surgery attached to St Bartholomew's Hospital are the enormous benefits that surgery has to confer on the large percentage of children with both Crohn's disease and idiopathic proctocolitis who require it. The surgical procedures described in this chapter have been accompanied by a remarkably low complication rate, dispelling the impression that morbidity in such cases would be high. This must in large measure be due to the fact that the children who come to surgery are in as good a state of nutrition as can be achieved by means of the various forms of enteral and parenteral feeding now available. Anxiety about healing of anastomoses and the development of fistulas after surgery for example, has not been a feature of the surgical care of these patients. The principal benefit of surgery has been a clear demonstration of an improvement in growth velocity in both Crohn's disease and idiopathic proctocolitis patients provided always that surgery is correctly timed. It is the author's experience that maximum benefit is achieved if the bulk of the diseased bowel can be removed. Plainly relief of symptoms such as abdominal pain and diarrhoea has also been rewarding. In many instances second procedures such as restorative proctectomy in idiopathic proctocolitis can be timed to fit in with educational commitments. In Crohn's disease the likelihood of recurrence in adult life is high but these patients are in a fit state to cope with further therapy including surgery should the need arise. From the management point of view the close cooperation between physicians and surgeons at all stages has been crucial, firstly to achieve smooth preparation prior to surgery and satisfactory after care. But of even more importance in the assessment of Crohn's disease is the presence of all clinicians involved in the case in the operating theatre so that the surgical options are fully assessed. This united approach avoids any unnecessary anxiety when, as inevitably happens, recurrence of symptoms due to relapse occurs. The involvement of patients of whatever age, and parents in all the decision making processes from the time of diagnosis has been vital. Early discussion about stomas involving members of the Stomatherapy Department has been invaluable. One final important aspect of the management of these patients is the seamless hand-over of care to an adult combined medical and surgical clinic at an appropriate time, usually at the age of 17 years.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8003742 TI - Unusual colitides. AB - Colitis is an important cause of abdominal pain and diarrhoea and is the main cause of blood and mucus in the stool. The inflammation can be due to infectious or to non-infectious causes, most commonly ulcerative colitis and Crohn's disease. However, a wide variety of rarer causes of colitis also present in childhood. These include colitis or enterocolitis secondary to Hirschsprung's disease and metabolic disorders (which include Hermansky-Pudlak syndrome, glycogen storage disease type 1b and pellagra). Primary inflammation of the colon is seen in microscopic and collagenous colitis, ulcerating enterocolitis of infancy, allergic colitis and autoimmune enteropathy. The histological pattern of each of these diseases has a characteristic picture and separates them from each other from ulcerative colitis and Crohn's disease. The pathophysiology of these rare forms of colitis in childhood is not clear; but in the future they may give us an insight into the pathogenesis of large bowel inflammation, particularly when the colitis occurs secondary to an established disease. PMID- 8003743 TI - Pathology of chronic inflammatory bowel disease in children. AB - The term chronic inflammatory bowel disease is usually applied to the idiopathic varieties ulcerative colitis and Crohn's disease but actually encompasses a wide range of colonic inflammatory conditions, which in children includes indeterminate colitis, microscopic colitis, allergic colitis and Behcet's enterocolitis. The pathologist's opinion is considered the final arbiter in the diagnosis of inflammatory bowel disease but classification may be hampered by the considerable histological overlap between the various types of colitis. Accurate diagnosis, particularly in biopsy specimens, thus depends on clinical and radiological input as well as on appropriately selected and adequately prepared material. This chapter discusses in detail the morphological appearances of ulcerative colitis and Crohn's disease with particular emphasis on diagnosis by mucosal biopsy and differential diagnosis in the paediatric age group. The recent demonstration of ulceration-associated cell lineage and trefoil peptide expression in inflammatory bowel disease is also discussed. PMID- 8003744 TI - Clinical and diagnostic features of Crohn's disease and ulcerative colitis in childhood. AB - Crohn's disease and ulcerative colitis are important disorders in childhood which may present in a similar way to adult life, but the major paediatric dimension is impairment of growth and development which may occur in both disorders. Whilst the diagnosis of ulcerative colitis is usually quite quick by virtue of the pressing nature of the chief symptoms, bloody diarrhoea, the diagnosis of Crohn's disease may be significantly delayed in children as the symptoms are frequently less obvious and may not, at first, be gastrointestinal. Modern diagnosis is based upon a combination of endoscopy and radiology. Of particular importance is endoscopic biopsy which enables a definite histological diagnosis to be made. Early referral to diagnostic centres is particularly important in childhood. PMID- 8003746 TI - The best and worst times for dialytic therapy are now. PMID- 8003745 TI - Growth and puberty in chronic inflammatory bowel disease. AB - The consequences of IBD during childhood and adolescence may be devastating in terms of loss of growth potential, particularly if there has been a clinical course of frequent relapses resulting in inadequate nutrition and associated with repeated courses of steroid treatment. There is to date, however, a paucity of data recording final adult heights in such patients. The anticipation of relapse should become easier with increasing awareness of the importance of parameters of growth and pubertal development. Early and intensive nutritional support, and the use of steroid-sparing agents should help reduce the frequency and severity of any height deficit. The performance and timing of surgery must take into account the child's status in terms of height velocity and pubertal development. The importance of inducing the remission before the onset of puberty is stressed and this remission should be sustained at all costs during the pubertal years so that valuable height is not lost as a consequence of a missed pubertal growth spurt. Thus, increasing awareness of the issues of growth and development in these patients should improve the accuracy of initial diagnosis and early recognition of relapse, such that these children are ensured the best possible provision for achieving their full height potential. PMID- 8003747 TI - Changing criteria for the artificial lung. Historic controls on the technology of ECMO. AB - Extracorporeal membrane oxygenation (ECMO) has developed over the past 4 decades of research to enjoy limited clinical success today as the state-of-the-art artificial lung for long-term use. The sustained efforts of clinicians, corporations, and research scientists may achieve the promise of membrane technology in the future: an implantable artificial lung. The clinical trials considered necessary for the validation of ECMO have introduced ethical and economic dilemmas for research and corporate interests, which are typical of the development of life supporting and life sustaining technologies. The evolution of patient selection criteria and techniques for clinical trials has relied on previously recorded data. This history shows that although ECMO has been applied in the past, controlled clinical trials remain controversial, and yet in both recent and retrospective studies, survival statistics have become encouraging for certain patients. PMID- 8003748 TI - Cardiac disease in chronic uremia. Pathophysiology and clinical epidemiology. PMID- 8003749 TI - The contribution of hypertension to dialysis patient outcomes. A point of view. PMID- 8003750 TI - Food and drug administration guidance sections. A new paradigm for medical devices. Committee for Clinical Review. FDA. AB - The data submitted for Food and Drug Administration (FDA) review of medical devices are often not approved because of poor study design. This article proposes a new approach for developing FDA study design guidance through panels of colleagues from the academic, federal, and private sectors. This piece focuses discussion and thought on Guidance Sections, similar to Study Sections of the National Institutes of Health, to serve as common ground for the continual upgrading of guidance documents through peer review and leading edge scientific and clinical judgement. PMID- 8003751 TI - Why make monofilament sutures out of polyvinylidene fluoride? AB - In recent years some clinical reports have associated suture failures with polypropylene monofilaments. Therefore there is interest in developing an alternative suture material that is less thrombogenic than polyester and similar in handling characteristics but less prone to mechanical failure than polypropylene. To this end, Peters Laboratoire Pharmaceutique has developed a new monofilament suture material from polyvinylidene fluoride (PVDF), which has been subjected to a special treatment to modify its crystalline form and level of crystallinity. The purpose of this study was to evaluate its mechanical, chemical, and biologic properties and to compare its performance, in a peripheral vascular application, to that of a polypropylene control. A series of in vitro tests were performed to study the morphology, tensile properties, creep, surface chemistry, thermal characteristics, and resistance to iatrogenic trauma. In addition, an in vivo trial was undertaken in which vascular prostheses anastomosed with either PVDF or polypropylene sutures were implanted as a thoracoabdominal bypass for 6 months in the dog. Histologic and degradation analyses were performed on the explants. The results from the mechanical tests on 4-0, 5-0, and 6-0 PVDF and polypropylene sutures demonstrated that although both materials have similar breaking strengths, the PVDF has a higher extension at break, has less delayed extension when under tensile creep testing, and suffers less trauma than the polypropylene when compressed by a standard needle holder. While chemical analyses found evidence of surface oxidation on both types of sutures, thermal analysis confirmed that the level of crystallinity of the PVDF polymer is higher than that of the polypropylene control. During the pilot study in animals, PVDF sutures were found to have good handling and frictional characteristics that facilitated the tying of knots. Histologic analysis of the explants found no inflammatory cells in the tissue surrounding either the PVDF or polypropylene sutures, and scanning electron microscopic examination of the cleaned suture surfaces found no evidence of degradation during 6 months in vivo. Though preliminary in nature, these findings indicate that monofilament sutures made from PVDF provide an attractive alternative to those made from polypropylene for use in cardiovascular surgery. In addition to providing acceptable in vivo behavior and being easy to manipulate and more resistant to iatrogenic injury, PVDF materials can be sterilized by beta or gamma radiation and so can reduce dependence upon ethylene oxide and chlorofluorohydrocarbons. PMID- 8003752 TI - Enzymatic glucose sensors. Improved long-term performance in vitro and in vivo. AB - We studied the long-term in vitro and in vivo performance of enzyme electrode glucose sensors. Single commercially produced enzyme-active membranes remained functional for estimating glucose in vitro for 14-36 months. These membranes were implanted subcutaneously in rats for 1 year and, upon explanation, remained functional for measuring glucose in vitro. Sensors with these membranes plus an additional outer membrane with lower glucose permeability allowed glucose monitoring in the low oxygen tension of subcutaneous tissue. These sensors were surgically implanted in three nondiabetic dogs. Each sensor implant was coupled to a radio transmitter to allow continuous long-term glucose monitoring in these awake unrestrained dogs. In vivo sensor performance was evaluated by intravenous glucose infusion, with reference blood glucose determinations made in the clinical laboratory. These subcutaneously implanted sensors tracked changes in plasma glucose for up to 12 weeks. The in vivo initial response for three sensor implants was approximately 35 sec (n = 8). Sensor peak response to glucose after bolus infusion ranged from 3 to 14 min. Stability of sensor sensitivity within +/ 15% for more than 1 month was demonstrated in two of the dogs. Sensor lifetime was limited not by loss of enzyme activity, but by biodegradation of the outermost polyurethane membrane. The findings suggest that long-term continuous monitoring of blood glucose using a subcutaneously implanted enzyme electrode sensor may be possible. PMID- 8003753 TI - Patient related factors leading to slow urea transfer in the body during dialysis. AB - We studied the trans compartmental speed of urea transfer by comparing concentration changes of blood urea nitrogen to mass changes of urea during 80 dialyses in six patients. The speed of urea transfer was studied as a dependent factor of 15 patient characteristics: age; gender; fluid overload; and pre and post values of and change in pulse and temperature, calcitonin gene related peptide, and mean arterial blood pressure. Concentration changes in blood urea nitrogen were measured as pre and post dialysis urea concentration, the total urea in the body was measured by pre dialysis urea and tritium total body water determinations, and the actual mass of urea removed by collecting all dialysate. As a mean, concentration of blood urea nitrogen fell 54% but the mass urea removed was only 40% for a mean ratio of 1.41. Nine factors were associated with the speed of urea transfer. Patients with fast transfer had more normal fluid balance, a normal pulse rate, body temperature, calcitonin gene related peptide values, and blood pressure both before and after dialysis. The patients with a slower transfer of urea had a lower blood pressure before and after dialysis and a more labile pulse rate and body temperature. Patients with unpredictable urea transfer were the most edematous and had the most labile blood pressure. It is important to know which patients have slow urea transfer. Such patients should not be treated by fast dialysis, and those with the slowest rates may do particularly well on continuous ambulatory peritoneal dialysis.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8003754 TI - The development of a valveless cardiac assist device attached to the ventricular apex. AB - Konstantinov et al, in October, 1991, published a novel way to bridge a patient for heart transplantation. They proposed to cut off both ventricles high under the atrioventricular groove, leaving the atria, aorta, and pulmonary artery and their valves intact and to attach pneumatically driven, valveless pulsating pouches to assist the heart until a donor could be found. The removal of the ventricles just below the atrioventricular groove is called the "high cut"; it, however, destroys the chordae tendineae rendering the mitral and tricuspid valves insufficient. These have to be replaced by tissue inflow valves. We chose to cut off the ventricles at a lower level (the "low cut") to leave the papillary muscles on both sides intact, thereby saving the integrity of the mitral and tricuspid valves. Pulsating pouches were made to fit the heart at this lower level. They can be easily connected to the remaining heart after a specially disigned cuff has been sutured over the ventricular stumps. The pouches were pumped during the systole of the natural heart, but the myocardium may have to be electrically stimulated during systole to prevent undue distension. If the turgor is too weak to prevent distension, a sleeve over the ventricles is provided. To find the best location for these pouches, human cadaver implantations were done and the pre peritoneal cavity was found to be the most suitable. In vitro testing to determine how much flow could be pumped was done by attaching the pouches to fresh pig hearts and connecting them to a double sided mock circulation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8003755 TI - Prosthetic valve endocarditis. An analysis of the outcome in 32 cases. AB - To evaluated the clinical results and risk factors with prosthetic valve endocarditis (PVE), we reviewed data on 32 patients who were hospitalized over a period of 10 years because of prosthetic valve dysfunctions secondary to endocarditis. The linearized incidence of PVE was 0.89% per patient year. Overall mortality was 34% (11 of 32 patients). However, the mortality differed depending upon the factors associated with PVE: medical treatment alone (100%, p < 0.001), early onset within 12 months (53%, p < 0.05), and complication with systemic emboli (80%, p < 0.05). In contrast, anatomic valve position, mechanical valves, female gender, microorganisms, and conduction abnormality did not appear to be significant risk factors. In the 25 patients with medical-surgical therapy, there were 4 operative deaths (16%, 4 of 25 patients). Pre operative New York Heart Association Class IV (p < 0.05) and reoperations on an urgent basis (p < 0.04) had a significant correlation with the operative mortality. On the basis of these results, the outcome of PVE can be improved if conditions predisposing to myocardial damage or complications leading to deaths are prevented with initial treatment by antibiotics and subsequent surgical intervention. PMID- 8003756 TI - The internal ventricular venting loop catheter. A new, simplified, single cannulation approach for a ventricular assist system. AB - The internal ventricular venting loop (IVVL) catheter is a coaxial, two lumen, bidirectional flow cannula introduced peripherally and advanced intraluminally to the pulmonary artery by its flow directed, balloon tipped inner tubing in a right ventricular assist system (RVAS), or to the left ventricle over a guide wire under fluoroscopy in a left ventricular assist system (LVAS). Its use was successfully tested in six acute canine experiments using a small IVVL catheter. Hemodynamic responses to increasing roller pump flow rates, to a maximum of 1 L/min, were initially measured. Then, hemodynamic changes to 600 ml/min, after left anterior descending artery ligation (in IVVL-LVAS) and 300 ml/min after right coronary artery ligation (in IVVL-RVAS) were regularly recorded every 15 min until cardiac arrest. The IVVL-LVAS was able to significantly decrease the pulmonary capillary wedge pressure, while the IVVL-RVAS was able to significantly decrease the central venous pressure. The IVVL system was able to partially unload the ventricles and restore about 33-60% of the cardiac output. However, it could not effectively support the heart during arrest. Thus, the IVVL catheter can facilitate simple and effective single cannulation for either RVAS or LVAS. This approach may enable ordinary cardiac centers to make use of already available blood pumps for temporary, inexpensive, and less invasive application of partially assisted circulation when intra aortic balloon pump assistance fails. PMID- 8003758 TI - A newly developed porcine heart valve bioprosthesis fixed with an epoxy compound. An experimental evaluation. AB - Concerns with currently available bioprostheses are calcification, long-term durability, and functional and hemodynamic performance. It has been well known that these concerns are all more or less related to the fixatives, glutaraldehyde or formaldehyde, used in preserving bioprostheses. To address these concerns, we undertook the development of a porcine bioprosthesis fixed with an epoxy compound. It was discovered that the porcine leaflets fixed with the epoxy compound appeared more natural than those preserved with glutaraldehyde. The performance of this newly developed epoxy compound bioprosthesis (three samples) was evaluated in a juvenile sheep model. The results were compared to those of its glutaraldehyde counterpart (three samples). Two-dimensional echocardiographic inspection of the valvular leaflet motion indicated that the epoxy compound leaflets were more pliable than their glutaraldehyde counterparts. In addition, the epoxy compound valve appeared to open more widely than the glutaraldehyde valve. Color Doppler flow mapping demonstrated that the blood flow distal to the epoxy compound valve was slightly broader than that observed distal to the glutaraldehyde valve. Moreover, at retrieval, less calcium and pannus ingrowth were observed in the epoxy compound valve than its glutaraldehyde counterpart. The results of this preliminary evaluation indicated that the performance of this newly developed epoxy compound valve was at least equivalent to its glutaraldehyde counterpart, if not better. PMID- 8003757 TI - Uptake of 3H-7-cholesterol along the arterial wall at an area of stenosis. AB - Abnormal uptake of atherogenic substances and lipid infiltration have been believed to contribute to the localized genesis and development of atherosclerosis, as well as to late failures of synthetic arterial prostheses. To verify the theoretical prediction that accumulation of lipoproteins on the luminal surface of arterial walls occurs in the regions of disturbed flow, we have carried out an in vitro mass transfer experiment to test the effect of a pseudo steady recirculation flow on the uptake of 3H-7-cholesterol by the arterial wall at a surgically created stenosis. It was found that, as predicted by the theory, in the flow field of the stenosis the uptake of labeled cholesterol reached a maximum around the reattachment point of the vortex distal to the stenosis, where the wall shear stress was lowest (zero). This value of the highest uptake rate was almost twice the average, whereas the uptake level was at a minimum at the stenosis itself where the wall shear stress was highest. The lowest uptake was only 60% of the average. These results provide strong support to our hypothesis, based upon the theory that, in addition to the flow induced changes to the biologic function of endothelial cells, the disturbed flow with slow recirculation itself favors the accumulation of atherogenic lipoproteins at the blood-endothelium boundary, therefore playing an important role in the localized pathogenesis and development of atherosclerosis. PMID- 8003759 TI - An optimal mounting frame to reduce flexural stresses of bioprosthetic heart valves. AB - Recent studies suggest that sharp bending of valve leaflets during the opening phase may be the reason for much of the mechanical failure of bovine pericardial bioprostheses. Sharp bending of the valve leaflets is promoted by the rigid, non expanding stents upon which the leaflets are mounted. We hypothesized that sharp bends and the associated flexural stresses could be significantly reduced by incorporating a stent that expands with the recipient aorta during systolic valve opening. We therefore modeled the opening and closing sequence of a trileaflet bovine pericardial valve with such an expanding supporting stent using our own finite element analysis software. Six different degrees of expansion were simulated, ranging from 2% to 25% expansion measured at the level of the stent post tips. Our results show that a 15% expansion is optimal, for the analyzed valve, because it eliminates the compressive flexural stresses at the commissures. Expansions below 15% were not sufficient to reduce flexural stresses, whereas expansions greater than 20% induced excessive tension in the valve cusps. PMID- 8003760 TI - The pulmonary valve. Is it mechanically suitable for use as an aortic valve replacement? AB - Pulmonary autografts have shown a low incidence of early failure and late structural deterioration when placed in the aortic position yet the potential value of the pulmonary valve as a replacement device has not been widely considered. Since the mechanical suitability of pulmonary valves for the high stress aortic position is unclear, we set out to define and compare the tensile mechanical properties of these two valves. We removed all 72 cusps from 12 fresh porcine aortic and pulmonary valves. Eighteen cusps from each of the two groups were fixed flat in 0.25% glutaraldehyde for greater than 24 hr. Circumferential or radial strips were cut from each cusp creating eight test groups, each with nine specimens. Stress-strain curves for each specimen were obtained using an Instron tensile testing machine. Stress-strain curves were obtained at 2, 10, 50, and 200 mm/min strain rates, each specimen was then strained to fracture. We found pulmonary leaflets were thinner than aortic leaflets (0.49 mm versus 0.67 mm) and glutaraldehyde fixation did not affect this relationship. The elastic moduli were comparable within the fresh and glutaraldehyde fixed treatment groups and within the circumferential and radial strip groups. Radial strips were more extensible than circumferential strips. Tissue viscous properties were similar and glutaraldehyde fixation produced minimal changes in stress relaxation rates. Tissue fracture tests emphasized tissue anisotropy with the failure point depending upon strip orientation. Glutaraldehyde had no effect on fracture stress but strain at fracture doubled due to increased collagen fiber crimping during fixation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8003761 TI - In vivo evaluation of a pulsatile impeller total heart. AB - For the in vivo evaluation of a pulsatile impeller total heart, biventricular assistance was performed in five pigs weighing 30-50 kg. The left pump delivered blood from the left atrium to the aorta, and the right pump from the right atrium to the pulmonary artery. The bypass flow on both sides was adjusted to about 40 50% of the total flow. Hematologic variables were measured every 2 hr during the 6 hr experiments. Results demonstrated that the pulsatile impeller total artificial heart causes no blood damage and can be used in chronic survival experiments. PMID- 8003762 TI - Implants and infections. From starfish to thrombus. PMID- 8003763 TI - Immune regulation of bacterial biofilm graft infection. PMID- 8003764 TI - Association between thrombosis and infection. PMID- 8003765 TI - Current concepts of thrombosis and infection in artificial organs. AB - Significant progress is being made on many fronts in the understanding and prevention of thrombosis and infections with artificial organs. It is likely that these advances will enable both implanted and temporary prosthetic cardiovascular devices to occupy an increasing role in clinical medicine in the future. PMID- 8003766 TI - Malacoplakia of the prostate in a renal transplant recipient. A complicated course. AB - Extrarenal malacoplakia in renal transplant recipients is generally associated with a good prognosis. We report the first case of malacoplakia of the prostate in a renal transplant recipient that was associated with a complicated course despite prophylactic antibiotic therapy and reduction of immunosuppression. Malacoplakia in a renal transplant recipient is not always benign. PMID- 8003768 TI - An interleukin-1 beta-induced noradrenaline release in the spleen is mediated by brain corticotropin-releasing factor: an in vivo microdialysis study in conscious rats. AB - The purpose of this study was to investigate whether an intraperitoneal injection of interleukin-1 beta (IL-1 beta) affects noradrenaline release in the spleen through its action on the brain of conscious rats. An in vivo microdialysis technique consisting of high-performance liquid chromatography with electrochemical detection was used for chronic monitoring of the splenic noradrenaline. The perfusion of a high concentration of K+ Ringer solution through the microdialysis probe significantly increased the concentration of noradrenaline in the spleen, while a perfusion of either Ca(2+)-free or tetrodotoxin-containing Ringer solution decreased the noradrenaline level in the dialysate. These results indicate that the noradrenaline recovered in the splenic dialysate is mainly derived from the nerve terminals of the splenic sympathetic nerve. The intraperitoneal injection of IL-1 beta (100 ng/kg) produced an immediate and significant increase in the noradrenaline levels in the spleen. The increased level reached a maximum level 40 min after injection and then gradually returned to the basal level. An intracerebroventricular (ICV) injection of a corticotropin-releasing factor (CRF) antagonist (alpha-helical CRF9-41, 30 micrograms) significantly attenuated the IL-1 beta-induced increase in the noradrenaline release. An ICV injection of CRF (2 micrograms) also caused a significant increase in splenic noradrenaline, which showed two distinct peaks at 20 and 140 min, respectively. These results suggest that the intraperitoneal injection of IL-1 beta facilitates noradrenaline release in the spleen through activation of the sympathetic nerve, and the increased sympathetic activity is, at least in part, due to the excitation of neurons containing CRF in the brain. PMID- 8003767 TI - Behavior and immune status of MRL mice in the postweaning period. AB - The notion that the MRL-lpr substrain is a useful model of behavioral and cognitive deficits found in systemic autoimmune diseases is supported by the recent findings of behavioral dysfunction in autoimmune MRL-lpr mice compared to their congenic control MRL +/+ mice. However, it has not been established whether the altered behavioral profile in MRL-lpr mice is the result of the autoimmune process itself or reflects a subtle difference in genetic background or both. To address the question whether MRL-lpr mice are born with behavioral dysfunction the present study compares the behavior of the two MRL substrains in the early postweaning period, when their immune status does not show detectable difference. Results show that the prediseased (4- to 6-week-old) MRL-lpr mice are not distinguishable from the congenic MRL +/+ controls on most behavioral measures except for speed of locomotion and novelty-induced hyperactivity in activity monitors. The immune status of the two substrains is also similar except for a lower hematocrit in the MRL-lpr group. Surprisingly, low amounts of antinuclear and brain-reactive antibodies (possibly transferred from diseased mothers) were detected in the serum of about 50% of the mice in both groups. The lack of major differences in behavior in the premorbid period suggests that appearance of previously reported behavioral dysfunction in the disease state reflects the presence of autoimmunity, time-determined genetic activation, or both. PMID- 8003769 TI - Morphine-induced decreases in in vivo antibody responses. AB - Endogenous opioids have been shown to be released during acute stress and could play a role in immune modulation and activation of the hypothalamo-pituitary adrenal axis. We investigated the ability of morphine sulfate to mimic stressor effects on decreases in in vivo antibody responses. Sprague-Dawley and Fischer 344 rats were given an intraperitoneal injection of an antigen, Keyhole limpet hemocyanin (KLH), followed by a single intravenous injection of either saline or varying doses of morphine sulfate. The corticosterone and anti-KLH IgG antibody responses to morphine were measured. A dose-dependent increase in corticosterone was observed. Significantly lower levels of anti-KLH IgG antibodies were observed in morphine-treated animals but these effects were strain and dose dependent. In Sprague-Dawley rats, 3 and 10 mg/kg doses of morphine decreased antibody levels while 1.5, 5, and 15 mg/kg did not change antibody responses. In Fischer 344 rats a dose of 5 mg/kg of morphine decreased antibody levels while 10 and 15 mg/kg did not change antibody responses. These results indicate that morphine can decrease antibody levels and that these decreases are not correlated with elevated levels of corticosterone. To determine if opioid binding is critical to these changes, animals received naltrexone prior to the administration of morphine. Naltrexone partially attenuated corticosterone levels, but completely blocked morphine induced changes in immune function. PMID- 8003770 TI - Inhibition of neural and neuroendocrine activity by alpha-interferon: neuroendocrine, electrophysiological, and biochemical studies in the rat. AB - In our earlier studies we have demonstrated that recombinant human interferon alpha 2A (rHu-IFN-alpha 2A) inhibits hypothalamo-pituitary-adrenocortical (HPA) secretion following both peripheral and central administration. Furthermore, this effect is antagonized by mu-opioid receptor antagonists, suggesting transduction by this subtype of opioid receptors. In the present studies, we demonstrate that this effect is also observed with the hybrid recombinant preparation, rHu-IFN alpha A/D, and a leucocyte-derived rat IFN-alpha preparation. The inhibitory effects on HPA activity were observed after intraperitoneal (i.p.) injections of rHu-IFN-alpha 2A (10(3) U), rHu-IFN-alpha A/D (10(4) U), and of Rat-IFN-alpha (1 and 10 U). Similar effects were observed with intracerebroventricular (i.c.v.) administration of all three IFN-alpha preparations. No increases in plasma concentrations of corticosterone were observed with doses of rHu-IFN-alpha A/D up to 10(6) U (i.p.) or 7 x 10(5) U (i.c.v.), but increases were found following i.c.v. administration of high doses of Rat-IFN-alpha (10(3) and 5 x 10(3) U). The inhibitory effects of all of the IFN-alpha preparations tested were antagonized by naloxone, but the stimulatory effects of 5 x 10(3) U Rat-IFN-alpha were not. Injections of rHu-IFN-alpha 2A (10(4) U i.p.) to urethane-anesthetized rats decreased the electrical activity of the majority of hypothalamic paraventricular nucleus neurons tested, including putative corticotropin-releasing factor secreting neurons antidromically identified as projecting to the median eminence. These electrophysiological data suggest that the decreases in HPA activity evoked by IFN-alpha are mediated by a rapid inhibitory effect at the level of the corticotropin-releasing factor-secreting neurons. The sensitivity of many central nervous system effects of IFN-alpha to mu-receptor antagonists strongly suggests that the cytokine serves as an endogenous opioid agonist arising from the immune system. In support of this hypothesis we have shown that SH-SY5Y human neuroblastoma cells, differentiated with retinoic acid treatment to express predominantly mu-receptors, are sensitive to rHu-IFN-alpha 2A in vitro. This sensitivity took the form of a dose-dependent inhibition of forskolin-stimulated adenylyl cyclase activity. The data yielded an IC50 (95% confidence intervals) value of 7.93 (5.70-11.04) nM for this effect. Neither undifferentiated SH-SY5Y cells nor NG108-15 mouse neuroblastoma x rat glioma hybrid cells (expressing delta-receptors) were affected by rHu-IFN-alpha 2A.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8003771 TI - Effect of one or more footshocks on spleen and blood lymphocyte proliferation in rats. AB - The effect of 1 (1.6 mA, 5 s), 3, 8, or 16 inescapable footshocks on the response of spleen and peripheral blood lymphocytes to nonspecific mitogenic stimulation and plasma corticosterone levels was studied in adult Lewis male rats. One footshock suppressed mitogenic activity in the spleen and this effect was comparable to 3, 8, and 16 footshocks. The maximum suppression to nonspecific mitogenic stimulation in the spleen was observed at 1 and 10 min after exposure to a single footshock and suppression of the mitogenic responses in the spleen persisted for at least 60 min. In contrast, immediately after a single footshock peripheral blood lymphocyte mitogenic function was not suppressed but instead was significantly enhanced. A significant suppression of mitogenic responsiveness of blood lymphocytes occurred 30 min after exposure to a single footshock and at 60 min the blood mitogenic activity did not differ from the home cage controls. Eight footshocks produced a significant suppression of mitogenic responses in the blood and 16 footshocks produced the greatest suppression of blood mitogenic function. These data suggest that 1 brief footshock caused activation of the HPA axis and sympathetic nervous system and resulted in significant alteration of the immune system. We suggest that noncomplex models of short-term stress may provide for a better understanding of the mechanisms underlying the development of stress reactions in the CNS and the periphery. PMID- 8003772 TI - Diurnal and acute stress-induced changes in distribution of peripheral blood leukocyte subpopulations. AB - In this study, we examined hormonal regulation of the distribution profiles of leukocyte subpopulations in the peripheral blood of rats. Flow cytometric analysis revealed significant and selective changes in the numbers and the percentages of peripheral blood leukocyte subpopulations which were a function of diurnal variations in hormone secretion and hormonal changes induced by acute stress. Changes in numbers and percentages of leukocyte subpopulations, which varied with time of day, were similar to changes observed under stress conditions. At the beginning of the rat's active period, and after 1 h of restraint stress, there was a significant reduction in numbers of leukocytes and lymphocytes. This reduction was primarily accounted for by a decrease in numbers of B cells, natural killer cells, monocytes (diurnal study), and helper T cells (diurnal study). There was also a significant decrease in the percentage of lymphocytes which was mirrored by an increase in the percentage of neutrophils in the peripheral blood. Peripheral blood leukocyte numbers were inversely related to plasma corticosterone levels. These results suggest that the endocrine system plays a role in the regulation of immune cell turnover and/or redistribution between immune compartments under conditions of normal daily experiences, namely, the diurnal cycle, and mild acute stress. They also suggest that these effects are selective for certain subpopulations of leukocytes. PMID- 8003773 TI - The influence of maternal separation on humoral and cellular immunity in farmed deer. AB - The effect of maternal separation on in vivo and in vitro immune parameters was studied in young hybrid deer. Groups of fawns separated from their mothers either 2 days prior to or 7 days post immunization with keyhole limpet hemocyanin were compared with a control group of immunized, unseparated fawns. Animals separated prior to antigenic challenge had significantly higher concentrations of antigen specific IgG in their serum than control animals. There was no influence on the humoral immune response in animals separated following immunization. In contrast, Con A transformations were transiently depressed in separated animals compared to the control group. The time separation was imposed relative to challenge and therefore influenced the subsequent immune response. PMID- 8003775 TI - Ofuji papuloerythroderma--pattern. PMID- 8003774 TI - An active amide group in the molecule of drugs that induce pemphigus: a casual or causal relationship? AB - Traditionally, drugs that are capable of inducing pemphigus are divided into two main groups according to their chemical structure, in particular, the existence of a sulfhydryl group in their molecule. Thus, two groups are formed: (1) drugs containing a sulfhydryl radical (thiol drugs or SH drugs) and (2) nonthiol or other drugs. Much emphasis has been put on the role of the sulfhydryl group in the pathogenesis of drug-induced pemphigus. The effects of this group have been extensively studied, and a logical paradigm on the mode of its action has been created. However, no attempt has been made to search for other biochemical radicals which might have an influence on the activation/triggering of this disease. The aim of the present report is to draw attention to a chemical group common to the molecule of several drugs that have been associated with the induction of pemphigus. Careful analysis of the chemical structure of nonthiol drugs known to induce pemphigus revealed that several of them share an active amide group in their molecule. We believe that this group might be responsible for the induction of the disease; thus, a third group of drugs capable of triggering pemphigus can be formed, namely drugs containing an active amide group. Several drugs of this group are discussed. PMID- 8003776 TI - Are psoriatic patients at risk of heat intolerance? Comments from a neuroscientist. PMID- 8003777 TI - How specific are major criteria for the diagnosis of atopic dermatitis? PMID- 8003779 TI - Eruptive syringoma: treatment with topical tretinoin. PMID- 8003778 TI - Melnick-Fraser syndrome. PMID- 8003780 TI - Imaging of skin epidermis from various origins using confocal laser scanning microscopy. AB - The ability to image the subsurface morphology of intact three-dimensional matrices such as skin epidermal tissue, using conventional optical microscopy, requires the tissue to undergo an extensive preparative protocol. This protocol includes fixing, embedding and physically sectioning the specimen. The process is slow and subject to sample perturbation, which can result in image misinterpretation. In this study, confocal laser scanning microscopy is used successfully for the imaging of the surface and underlying morphology of unlabelled and fluorescently labelled intact skin epidermal tissue, from various origins (that is human, pig and cultured epidermis). Unlike conventional optical microscopy, the technique requires little or no pretreatment of the tissue prior to imaging. Hence the technique is rapid, and the tissue experiences minimal physical perturbation and/or damage. Confocal images of skin epidermis in the reflected light (unlabelled) and fluorescent modes were obtained. In the reflected-light mode the detailed morphology of the various layers of the intact epidermis (that is the strata corneum, granulosum, spinosum and basale) from a variety of sources are clearly imaged. In the fluorescent mode, environment specific information is obtained. For example, topical application of the fluorescent probe acridine orange readily allows the confocal imaging of the nuclear material (nuclei and nucleoli), from cells of the different strata of intact epidermis. In the case of the fluorophore Nile red, however, visualisation of the lipid material of the epidermis, including the intercellular lipid of the stratum corneum and the lipid granules of the stratum granulosum, is possible. he reflectance and fluorescence confocal images are sel-consistent and agree with images obtained by conventional, physical sectioning protocols.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8003781 TI - Antibodies to centromere and centriole in scleroderma spectrum disorders. AB - The importance of early detection of scleroderma spectrum disorders (SSD) has been emphasized. We determined the clinical distribution of anticentromere antibody (ACA) and anticentriole antibody in the following four groups: (1) 264 patients with SSD, including 193 with systemic sclerosis, 29 with mixed connective tissue disease and 42 with suspected secondary Raynaud's phenomenon (RP); (2) 26 patients with primary RP; (3) 248 patients with other connective tissue diseases, and (4) 139 patients with other skin diseases. The frequency of ACA was significantly higher in SSD (78/264, 30%) than in the other groups. In patients with SSD, the incidence of ACA in suspected secondary RP (28/42, 67%) was similar to that in type I systemic sclerosis (24/36, 67%). Anticentriole antibody was detected in only 1 patient with suspected secondary RP (0.4%) out of the 264 SSD patients. These data indicate that anticentriole antibody is very rare and that the antibodies against mitosis-related antigens such as centromere and centriole are associated with early SSD. PMID- 8003782 TI - Total serum immunoglobulins and atopic symptoms in patients with vitiligo. AB - Serum concentrations of immunoglobulins were quantified in 110 patients with vitiligo, and the association with atopy was studied. Patients with vitiligo and simultaneous atopy presented lower IgE and higher IgA values compared to a reference group of patients with atopy alone. PMID- 8003783 TI - Antinuclear antibodies in patients with atopic dermatitis and severe facial lesions. AB - BACKGROUND: In adult patients with atopic dermatitis (AD), the presence of autoantibodies such as anti-IgE and antinuclear antibodies (ANA) has been demonstrated. The patients may have altered immune regulation. OBJECTIVE: The purpose of this study is to examine the prevalence of ANA in AD patients with severe facial eruptions and to evaluate the differences between ANA-positive and ANA-negative AD patients. METHODS: ANA, blood eosinophil count, total serum IgE levels, specific IgE antibody to Dermatophagoides pteronyssinus, disease duration, photosensitivity and association with respiratory allergic diseases were checked in 89 AD patients. RESULTS: Twenty-three (25.8%) AD patients showed positive ANA at titers ranging from 1:40 to 1:640, and the incidence of positive ANA was 12.1% in controls. Twenty-five (71.4%) of 35 AD patients with positive ANA at titers ranging from 1:20 to 1:640 were females. CONCLUSION: Adult AD patients with severe facial lesions should be examined for serum ANA. Particularly in female and photosensitive AD patients with severe facial lesions, serum autoantibodies have to be carefully investigated to differentiate from autoimmune diseases. PMID- 8003784 TI - Frequency and significance of the major and minor features of Hanifin and Rajka among patients with atopic dermatitis. AB - In 481 patients with atopic dermatitis (AD), 4 major features of Hanifin and Rajka were found in 72%, and in 96% over 6 minor features were seen, which is much more than the minimum required by these authors for making a 'firm diagnosis'. The incidence of particular minor features in all patients was varying significantly, and in subgroups of patients they appeared with different frequency. For example, asthma occurred more often in AD patients with the onset of skin lesions before the 6th month of life, and food intolerance was more frequently observed in patients with very high serum IgE level. In the control groups some minor features also occur but less frequently than in AD patients. We conclude that the anterior neck folds and Dennie-Morgan infraorbital fold should be regarded as minor AD features. PMID- 8003785 TI - Systemic amyloidosis. A report of 19 cases. AB - Systemic amyloidosis is a rare disorder and usually occurs in aged persons with a poor prognosis. Certain mucocutaneous symptoms and signs may act as important clues for diagnosis. Skin or tongue biopsy may also provide important information to establish a firm diagnosis. During the past 14-year period, we found 19 cases of systemic amyloidoses: 8 (42%) with primary systemic amyloidosis, 8 (42%) associated with multiple myeloma and 3 (16%) were secondary amyloidosis. Ages of the patients ranged from 52 to 71 years with a mean age of 62 years at diagnosis. Median survival was only 8 months. Mucocutaneous manifestations were found in both primary type and myeloma-associated amyloidosis. In addition to the existence of amyloid in tongue and rectum biopsies in 17 cases and abdominal fat aspiration in 1 case, biopsies from clinically normal-looking skin also showed positive results in 18 out of 19 cases. PMID- 8003786 TI - The nude mouse model for the study of human skin disorders. AB - Normal human skin grafted onto the nude mouse can be maintained without any signs of rejection throughout the life-span of the animal. Indeed, the nude mouse model is a powerful tool for understanding the pathological process of the skin. Until now many skin diseases such as psoriasis, cutaneous lupus, pemphigus and vitiligo have been looked at using the nude mouse model, which has helped to clarify the role of the various factors involved. PMID- 8003787 TI - Metastases from squamous cell carcinoma of the skin in southern Australia. AB - BACKGROUND: The frequency with which squamous cell carcinoma (SCC) of the skin metastasizes is a matter of dispute. Studies from private practices have reported much lower rates than hospital-based surveys, and one school of thought is that SCCs which arise in sun-damaged skin have a low risk of metastasis. METHODS: A prospective study of out-patients with histologically confirmed SCC was undertaken in southern Australia, a region with a very high incidence of skin cancer. RESULTS: Between November 1988 and November 1989, 481 patients were entered into the study and 420 followed for at least 3 years. An SCC was the initial diagnosis for 73 patients, 3 were immunosuppressed and 2 had an SCC of the lip, leaving 68 immunocompetent patients with SCC of the skin. Metastatic SCC developed in 2 patients (5.8% adjusted for losses) within 3 years. The SCCs were small and arose in sun-damaged skin. CONCLUSION: Patients with SCC of the skin need a careful follow-up because of the risk of metastasis. PMID- 8003788 TI - Sunscreen sensitization: a three-year study. AB - BACKGROUND: In the last decade UV filters have been incorporated in a large number of cosmetic products. OBJECTIVE: The purpose of our study was to evaluate the prevalence of sunscreen allergy in patients with a suspected photodermatitis. METHODS: 108 patients were patch-tested with the Gruppo Italiano Ricerca Dermatiti da Contatto e Ambientali (GIRDCA) standard series and photopatch-tested with the photopatch series. RESULTS: Allergy and/or photoallergy to sunscreening agents was diagnosed in 8 subjects (7.4%). Oxybenzone was positive in 4 patients, isoproyl dibenzoylmethane in 3 patients, p-aminobenzoic acid and 2-ethylhexyl-p methoxycinnamate in 1 patient, respectively. CONCLUSION: Our results obtained during a 3-year period (January 1990 to June 1993) confirm that sunscreens are presently the commonest photoallergens. PMID- 8003790 TI - Effects of oral isotretinoin on human auditory brainstem response. AB - BACKGROUND: Accumulating evidence suggests that synthetic retinoids may be capable of affecting the differentiation and growth of nervous tissue in vivo and in vitro. On the other hand, adverse reactions concomitant with brainstem involvement definitely or probably related to oral retinoid therapy have been reported in a small number of patients. OBJECTIVE: The purpose of the present study was to substantiate the possible effects of oral isotretinoin on the synaptic activity and propagation of action potentials along the nerve fibers. METHODS: The auditory brainstem response of 33 patients with severe nodulocystic acne before and 3 weeks after the onset of oral isotretinoin administration was investigated using auditory evoked potentials. RESULTS: The paired analysis of the response variables before and after treatment failed to reveal any statistically significant differences. However, a marked increase in latencies and interpeak latencies and a decrease in amplitudes for both ears were found in 3 patients after therapy. CONCLUSIONS: It seems reasonable to suggest that these subclinical changes may be due to an isotretinoin-induced synaptic malfunction or to a conduction defect in the auditory nerve fibers. PMID- 8003789 TI - Patch test reactions to the acetone-soluble fraction of human dander in atopic dermatitis. AB - An acetone-soluble fraction of human dander provoked positive patch test reactions in 45 (38%) of 120 patients with atopic dermatitis. The positive patch tests were rare in normal controls and clinical controls. The positive patch test reactions histologically showed spongiosis and mononuclear cell migration in the epidermis, edema and mononuclear cell infiltrate in the upper dermis. Scratch tests with the acetone-soluble human dander fraction were positive in only 2 (2%) of the 120 patients examined. It was suggested that in a considerable number of patients with atopic dermatitis, an acetone-soluble fraction of human dander provokes a delayed-type skin reaction without inducing an immediate-type skin reaction. PMID- 8003791 TI - Topical 0.3% and 0.5% podophyllotoxin cream for self-treatment of molluscum contagiosum in males. A placebo-controlled, double-blind study. AB - BACKGROUND: Molluscum contagiosum is generally a self-limiting benign skin disease that affects mostly children and young adults. OBJECTIVE: The purpose of this multicenter, double-blind, placebo-controlled study was to compare the clinical efficacy and tolerance of 0.3% and 0.5% podophyllotoxin in a hydrophilic cream base to cure molluscum contagiosum in Asian males. METHODS: Preselected patients (n = 150), age range 10-26 years (mean: 15.4), harboring 1,125 lesions (mean: 7.5), with size ranging from 2 to 8 mm in diameter (mean spot size 3.2 mm) and biopsy-proven diagnosis of molluscum contagiosum, were randomly allocated to three parallel groups. Twenty-four (16%) patients had atopic dermatitis. Patients self-administered placebo, 0.3% or 0.5% podophyllotoxin cream, twice daily for 3 consecutive days, and if total elimination was not achieved with one trial (6 topical applications), the same treatment was extended to 3 more weeks (24 topical applications in 4 weeks). The duration of the study was 12 weeks with 6 months (on monthly basis) follow-up. By the end of the treatment 80 patients (52, 92 and 16% patients in the 0.3%, 0.5% and the placebo groups, respectively) were evaluated as completely cured. During the treatment 92 patients (61.3%) did not complain of any allergic or localized adverse symptoms. Tolerable moderate to mild frequent side effects were pruritus (20.6%) and erythema (18%), with no dropouts. No recurrence was seen after 9 months of follow-up. Response to the trial medications appeared to be directly proportional to the concentration of podophyllotoxin (p < 0.001). Self-medication was well accepted by all the patients. It was concluded that the 0.5% podophyllotoxin cream preparation was more efficacious than the 0.3% incorporation (p < 0.001) and can be considered a safe, home-based first line of therapy to cure molluscum contagiosum. PMID- 8003792 TI - Neutrophilic dermatosis: a case of overlapping syndrome with monoclonal antineutrophil cytoplasmic autoantibody activity. AB - A 66-year-old male patient presented, over a 10-year period, polymorphic cutaneous manifestations with extensive neutrophilic infiltration which supports the diagnosis of overlapping syndrome of neutrophilic dermatoses. This was associated with a benign monoclonal gammopathy of IgA lambda type that had antineutrophil cytoplasmic autoantibody (ANCA) activity. Neutrophilic dermatoses may be associated with or can trigger ANCA. PMID- 8003793 TI - Necrolytic migratory erythema without glucagonoma in a heroin-dependent patient. AB - We described a case of necrolytic migratory erythema without glucagonoma in a 33 year-old man. The patient had been heroin-dependent, HIV negative since the age of 23. He had no medical history of note and all the investigations revealed normal parameters. This is the first case of necrolytic migratory erythema without glucagonoma associated with heroin abuse. PMID- 8003795 TI - The coexistence of linear and giant porokeratosis associated with Bowen's disease. AB - Linear and giant porokeratosis are both rare variants of this disorder of keratinization. We present a case exhibiting the clinical features of both variants coexisting in one patient, which to our knowledge has not been described previously. Furthermore, Bowen's disease was found to be present in the giant lesion, reflecting the enhanced risk of malignant transformation of this rare subtype of porokeratosis. PMID- 8003796 TI - Penicillamine-induced elastosis perforans serpiginosa treated successfully with isotretinoin. AB - Elastosis perforans serpiginosa (EPS) and the elastotic changes of pseudoxanthoma elasticum (PXE) are rare but well-recognized side-effects of long-term penicillamine therapy. A 42-year old female patient who developed both of these cutaneous side-effects following treatment with high-dose penicillamine for Wilson's disease is described; near-complete resolution of the EPS, but not the PXE was achieved by treatment with isotretinoin (0.5 mg/kg/day) for 6 weeks, despite continuation of the penicillamine. PMID- 8003794 TI - Cutaneous malignant melanoma appearing during photochemotherapy of mycosis fungoides. AB - We report a case of malignant melanoma that appeared in a 56-year-old man with mycosis fungoides (stage Ia) during treatment with PUVA. The cumulative UVA dose was 1,177 J/cm2. The pigmented lesion was removed and PUVA therapy discontinued. Histological examination revealed a superficial spreading malignant melanoma (1.77 mm thick, Clark level IV). The delayed-type cutaneous hypersensitivity was studied. The presence of a second malignancy after mycosis fungoides and PUVA therapy may have been coincidental. Nevertheless, this case suggests that the immunosuppression induced by mycosis fungoides and by PUVA therapy might be a pathogenetic factor in the development of malignant melanoma. PMID- 8003797 TI - Vimentinoma, an unusual neoplasm of the skin. AB - We report an unusual benign neoplasm that developed in a child. Tumoral cells were filled with vimentin intermediate filaments. No other features of differentiation were found by immunohistochemistry and electron microscopy. 'Vimentinoma' appears to be the most appropriate name for this neoplasm. PMID- 8003798 TI - Histiocytoid hemangioma with prominent fingernail involvement. AB - Only 2 cases of histiocytoid hemangioma localized in the nail apparatus have been reported in the literature. We describe here a patient affected by multiple histiocytoid hemangiomas involving the 3rd right digit and fingernail. The pathological features were typical for a diagnosis of histiocytoid hemangioma showing vascular proliferation characterized by enlarged endothelial cells associated with inflammatory cells. Phenotypic characterization of the proliferating cells confirmed their vascular origin. PMID- 8003800 TI - Proliferating trichilemmal cyst arising in the arm of a young woman. AB - An 18-year-old woman with a proliferating trichilemmal cyst arising in her arm is described. Histological examination revealed typical features. This is the second reported case of such a site. Our case is unusual both in age and location. PMID- 8003799 TI - Adhesion molecules in lymphomatoid granulomatosis. AB - The expression of some adhesion molecules of the integrin family and their ligands was investigated in skin biopsies from a patient with lymphomatoid granulomatosis (LG), who at onset presented cutaneous lesions followed by lung and brain involvement. The angiocentric and angiodestructive skin infiltrate consisted mainly of T helper 'memory' cells (CD2+, CD3+, CD4+, CD5+, CD7+, CD45RO+) with a variable expression of activation antigens (CD25-, CD38+, CD71+, HLA-DR+) and 20% Ki67+ (nearly all atypical cells). T cells highly expressed alpha 3 beta 1 and alpha 5 beta 1 integrins, along with integrins of the beta 2 family. A modification of the expression pattern in laminin and collagen IV and an increased expression of tenascin and fibronectin were also observed. PMID- 8003801 TI - Self-healing localized cutaneous mucinosis. AB - A 54-year-old woman presented a lesion on the dorsum of the right hand. Routine laboratory tests were normal or negative. Histological examination revealed mucin deposits in the reticular dermis. The lesion cleared within 1 year without any treatment but biopsy. This case does not fit the diagnostic criteria of any known cutaneous mucinoses. PMID- 8003802 TI - Annular atrophic lichen planus. AB - We describe the second case of annular atrophic lichen planus. The annular configuration of the lesions resulted from peripheral enlargement with simultaneous central clearing. Histology showed features of lichen planus in the active border of the lesion and a pattern of resolved lichen planus in its center. Elastic fibers had been destroyed in the papillary dermis both in the border and in the center of the lesion, resulting in an atrophic appearance of the lesion. Annular atrophic lichen planus is an uncommon variant of lichen planus that results from elastolytic activity of inflammatory cells with formation of areas of localized acquired cutis laxa. PMID- 8003803 TI - Coexistence of morphea and systemic sclerosis. PMID- 8003804 TI - Ultrastructure of spontaneous glomerular lesions in syrian hamsters of APA strain. AB - Electron microscopic observations were carried out on the spontaneous glomerular lesions in male APA hamsters from 3 to 12 months of age. Until 6 months of age, focal expansion of mesangial region due to an increase of matrix material and mesangial cells was characteristic, and segmental thickening of capillary basement membrane and partial effacement of foot processes of podocytes were also sometimes observed. At 12 months of age, although all of these changes became more severe, the most prominent alteration was found in podocytes, which showed various degenerative changes. No deposition of amyloid fibrils was detected in any portion of the glomerulus. PMID- 8003805 TI - Ultrastructural alterations of the rabbit sciatic nerve, spinal cord and cerebellum, following methionine sulphoximine administration. AB - Methionine sulphoximine (MSO) is a centrally acting neurotoxin which inhibits the glutamate metabolism enzymes and has convulsive properties. Small doses of MSO were administered to rabbits, either intravenously (i.v.) or intracerebroventricularly (ICV), and electron microscopic examination of the cerebellum, the spinal cord and the sciatic nerve was performed on the first day of rabbit hind leg rigid paralysis (myopathy with histological findings resembling myositis), which set in by the 2nd to 4th day after MSO administration. In the cerebellum focal minor alterations were found in the astrocytes (swelling and lucidity, diminution of glycogen granules) and sparsely in the presynaptic terminals (lucidity and clumping), whereas most of the neuron presented a normal appearance. In the spinal cord and in the sciatic nerve a dissociation of the axon from the myelin sheath was evident in a small number of myelinated nerve fibres, along with the appearance of vacuolated spaces. Mitochondrial disorganisation in the axons, as well as glial cell alterations, were also seen. The ultrastructural alterations were non specific, and since they were induced 2 to 4 days after the administration of either minimum doses (i.v.) or of extremely low doses (ICV) of MSO, they may be attributed to the inordinate increase of metabolism during the period of convulsions. PMID- 8003806 TI - Histochemical study of the blue autofluorescence of collagen in oral irritation fibroma: effects of age of patients and of the duration of lesions. AB - The intensity of the autofluorescence of collagen was measured in 27 irritation fibromata of the buccal mucosa and 13 of the lip. The intensity of fluorescence correlated positively with the duration of the lesion. The fluorescence intensity also increased with the patients' age. The present observations show that in irritation fibromata of buccal and lip mucosae, the intensity of blue autofluorescence of the collagen increases with duration of the lesions and with the age of patients. PMID- 8003807 TI - Fine autoradiographical study on scale morphogenesis in the regenerating tail of lizards. AB - Regenerating scales in lizards originate as pockets in the epidermis instead of epidermal elevations as during embryo development. The morphogenesis of scales in the regenerating tail of the lizards. Anolis and Lamphropholis was studied after peritoneal injection of 3H-thymidine. The tracer was localized in the forming epidermis after progressive post-injection times, by means of autoradiography on plastic sections. After 4-5 hours post-injection of 3H-thymidine, the radioactivity was localized in the basal layer. After 2 to 4 days post-injection labelled cells were seen in the basal and intermediate spinosus layers but not in the uppermost keratinizing layers. Labelled cells were seen in the differentiating cornifying layers (pre-beta and pre-alpha) 6-8 days post injection. At 12-14 days post-injection almost no radioactivity was seen in the basal layer or in the living part of the epidermis. A few labelled cells were present in the dense keratinizing layers of the sloughing wound and interscale lacunar layers. This study shows that scale formation and morphogenesis in the regenerating tail is brought about by a localized cell proliferation along the regenerating epidermis. In the forming scales the percentage of labelled cells in the distal side (future dorsal part of the new scale) is much higher than in the proximal side (the future ventral side of the scale), so that overlapped scales are generated. PMID- 8003808 TI - Multivariate discriminant analysis of normal, intraepithelial neoplasia and human papillomavirus infection of the uterine cervix samples. AB - The present investigation studies the role of multivariate statistical methods on quantitative histopathological features of cells in uterine cervix epithelium to discriminate between normal and abnormal uterine cervix samples. 143 histological specimens were included in the study involving normal cervix, cervical intraepithelial neoplasia (CIN) lesions and cervical human papillomavirus (HPV) infection with and without CIN (condyloma-CIN and condyloma-NCIN groups, respectively). Deep, middle and superficial regions of the cervical squamous epithelium were morphometrically analyzed. Identification of normal cervix from pathological cases was highly achieved with a specificity of 100%. The application of discriminant statistical method within pathological specimens showed an acceptable percentage of cases correctly classified; thus, an efficiency of 83.0% and 74.6% was obtained in order to discriminate within CIN and condyloma-CIN grades respectively. These percentages increased when differentiation between each grade of CIN versus condyloma-CIN were considered, using only 1-3 morphometrical parameters. Our findings indicate that the combination of nuclear and cytoplasmic quantitative features, specially size parameters, permit a high correct percentage classification of cervix samples. The discrimination process was better when few diagnostic categories were included; however, 100% specificity for normal samples was always reached. PMID- 8003810 TI - Regional differences in cell surface patterns in normal human sulcular epithelium. AB - Studies with scanning electron microscopy in the normal human sulcular epithelium are scarce, and no precise information exists about cell surface patterns along the epithelium, the frequencies of these patterns, or possible regional differences within the mouth. In five periodontal biopsy specimens each from the anterior and posterior region of the mouth, we observed three cell patterns on the basis of the overall appearance of morphological surface markers in the coronal and apical zones of sulcular epithelium: microvilli; microplicae; and pits. The percentage of keratinocytes showing the microvillous pattern in the surface of apical sulcular epithelium of the posterior region of the mouth was significantly higher than in the anterior region. We posit that the presence, in the bottom of the normal sulcular epithelium in the posterior region of the mouth, of mainly microvillous keratinocytes (the most undifferentiated and least desquamative type of keratinocyte, and thus the most vulnerable to bacterial colonization) can be associated with observations of longitudinal clinical studies of periodontal disease, which suggest that more severe clinical findings are found in the region of the molars. PMID- 8003809 TI - Histochemical and morphometric study of the cricoarytenoideus lateralis muscle in the horse. AB - Histochemical and morphometric parameters of the cricoarytenoideus lateralis muscle of the horse are presented. Using myosin ATPase staining after acid preincubation, 3 fibre types (I, IIA and IIC) were identified. Using NADH-TR staining, type I fibres showed high oxidative capacity, whereas type II fibres had high or low oxidative capacity. The type I to type II ratio was of 35:65. This ratio remained constant in the age range examined. Statistically significant (p < 0.01) differences were found in values for fibre size between groups of horses weighing more than 500 kg and less than 400 kg. Mean area of type II fibres was greater (p < 0.001) than that of type I fibres. There were no significant differences in mean area between left and right muscles in the group of animals with less weight. In contrast, significant differences (p < 0.05) in mean area between left and right muscles were found for type I fibres in the group of animals exhibiting a higher weight. The histographical distribution of fibre type areas was unimodal. Most adult horses showed muscle fibre type grouping in the left muscle. PMID- 8003811 TI - Pulmonary response to bovine albumin. A morphometric study in rats. AB - The following hypothesis is proposed: that hypersensitivity pneumonitis (HP), experimentally induced in rats, is the cause of a thickening in the alveolar wall, a decrease in the size of the alveole, hyperplasia in the bronchus associated lymphoid tissue (BALT) and hypertrophy in the goblet cells. Wistar rats were classified into two different groups, namely, non-treated animals and animals exposed to bovine albumin (BA). A morphometric study was carried out and the following variables were quantified: a) percentage of lymphocytes, neutrophils and alveolar macrophages of the bronchio-alveolar lavage (BAL); b) the interstice of the alveole, the alveolar chord length, the alveolar wall thickness and the number of alveolar macrophages with hemosiderin within its cytoplasm; c) the size of lymphatic area (LA) in BALT, the length of the lymphatic epithelium (LEp) in BALT and the percentage of goblet cells in the bronchial epithelium. The following results were obtained from the animals exposed to BA: 1) a significant increase in both lymphocytes and neutrophils of BAL, and of alveolar macrophages with hemosiderin in its cytoplasm; 2) a significant thickening of the alveolar walls and the BALT elements, which confirms the above mentioned hypothesis; 3) a significant increase in the alveolar chord and a significant decrease in the number of goblet cells of the bronchus, which contradicts the above mentioned hypothesis.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8003812 TI - Contribution of carbohydrate histochemistry to glycobiology. AB - The physiological importance of carbohydrate biology has gradually emerged from a lot of recent information on protein-carbohydrate and carbohydrate-carbohydrate interaction in normal and pathological conditions. After considering the conventional methods which allowed researchers to differentiate glycan-containing macromolecules from other complex compounds (nucleic acids, proteins), selected topics of intracellular and cellular organ architecture are focused upon in which the use of lectins and neoglycoproteins as histochemical reagents has opened new horizons for the localization of glycoconjugates in situ and the elucidation of their often still enigmatic functions. The authors hope to place into perspective that such glycohistochemical studies will strongly contribute to the progress in the dynamically growing field of glycobiology. PMID- 8003813 TI - Exoglycosidases and lectins as sequencing approaches of salivary gland oligosaccharides. AB - This review was focused on the salivary gland oligosaccharide chains studied by lectin histochemistry combined with exoglycosidase digestion. Glycoconjugates play an important role in many biofunctions and, generally, salivary mucins, which consist of numerous oligosaccharide chains attached at closely spaced intervals to a peptide backbone, serve as lubricants and protective agents, but in many instances we are ignorant about the role of biochemically identified oligosaccharides. Lectin histochemistry represents the greatest analytic tool to study carbohydrates in situ; in addition, there is availability of selective enzymes, so glycosidase degradation is useful to both investigate the structure of a given oligosaccharide and verify the influence of neighbouring sugars on the affinity towards the respective specific lectins. Using stepwise digestion of samples, followed by lectin labelling, the structure of terminal short oligosaccharides with blood-group activity was also elucidated. Additional histochemical methodologies were developed to establish the presence of acetylated groups in sialic acid residues, and the position of the linkage to the underlying monosaccharide. Sequencing approaches by exoglycosidases and lectins were also seen to be particularly useful when substantial differences did not emerge in lectin affinity, glycoconjugate composition and complex carbohydrate cytochemistry. PMID- 8003814 TI - Histopathological characterization of photochemical damage in nervous tissue. AB - This paper discusses histological and ultrastructural changes produced by dye sensitized photoreactions in the central and peripheral nervous system. Particular attention has been given to morphological outcome in experimental models which reproduce widespread clinical pathologies, e.g. stroke, spinal cord injury and peripheral neuropathy. Evaluation of structural alterations may not only help to characterize the evolution of these disease processes but also allow us to study possibilities of therapeutic intervention. PMID- 8003815 TI - The role of the proteasome in cellular protein degradation. AB - Eukaryotic cells contain a major intracellular proteolytic activity known as the proteasome. The proteasome is a strongly conserved cylindrical structure of high molecular weight (650 kDa, approximately 20 S) and demonstrates multiple endopeptidase activities. The general structural, biochemical and genetic features of the proteasome are conserved from archaebacteria through yeast to humans. This structure fulfills an essential role by functioning as the proteolytic core of a 26 S multienzyme complex responsible for the energy dependent degradation of ubiquitinated proteins. The bulk of intracellular proteolysis appears to be through the ubiquitin-dependent pathway. Incorporation of the proteasome into the 26 S multienzyme complex appears to confer both a specificity for ubiquitinated proteins as well as a means to tightly regulate proteolytic activity. Thus, one function of the proteasome is required for the degradation of either abnormal or certain regulatory proteins by the ubiquitin pathway. Proteasome subunits appear to be encoded by a related gene family as defined by extensive sequence similarities. The gene products are confined to either of two general classes: alpha-type which appear to be structural and beta type which may be catalytic. Genes encoding at least two proteasome subunits map to the Major Histocompatibility Complex. Accumulating evidence points to the proteasome (or a specialized form) participating in the cytosolic degradation of these viral proteins upon cellular infection.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8003816 TI - The prognostic importance of the morphological subdivision of the grade II superficial bladder cancer. AB - In this study a morphological subdivision of grade (g)II superficial bladder cancer is proposed and correlated with recurrence and progression rate. Forty patients, 33 males and 7 females, of 70 years mean age, with initial gII superficial transitional bladder cancer were treated with transurethral resection between January and December 1987 with follow-up for a mean period of 4 years. Recurrences were observed in 24 patients. All histological specimens were reviewed and reclassified to gIIa and gIIb mainly according to the variation in nuclear size, the degree of nuclear atypia and the number of mitoses. 42.1% (8/19) of the gIIa and 76.2% (16/21) of the gIIb tumors recurred. The observed difference in recurrence rate was statistically significant (s.s)-p < 0.05. The disease-free interval after the initial presentation was over two years in 50% (4/8) of gIIa and in 6.25% (1/16) of gIIb patients (s.s. difference-p < 0.05). None of the patients with gIIa, but 37.5% (6/16) with gIIb urothelial cancer had more than two recurrences (s.s. difference-p < 0.05). All gIIa recurred as gIIa superficial cancers, 62.5% (10/16) of gIIb as gIIb (5 superficial and 5 invasive) and the remainder 37.5% (6/16) as invasive gIII tumors. Only one patient with repeated recurrences died two years after the initial presentation. 3 patients died from other causes. IN CONCLUSION: 1. The morphological subdivision of gII urothelial cancer into gIIa and gIIb has a prognostic significance, as it is related to the recurrence rate, the disease-free interval after the initial resection, the number of recurrences and the progression rate.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8003817 TI - Effects of in utero exposure to low dose ionizing radiation on development in the rat. AB - Most studies of in utero effects of ionizing irradiation involve high doses and examination at postnatal intervals. Little information is available on the effects of low levels of ionizing radiation on embryogenesis. The developmental effects of in utero exposure to 50 cGy gamma radiation on gestational day-9.5 was investigated using Sprague-Dawley rats. Irradiated rats and appropriate controls were killed at prenatal intervals of 4h, 48h and 10 days after exposure. Fetuses were examined for abnormalities and random samples of tissues were prepared for microscopic study. With the exception of the neuroepithelium, no histopathological changes were observed in embryos 4h after exposure to 50 cGy. In irradiated embryos, mitoses were reduced within the neuro-epithelium; pyknosis and some necrosis of cells were apparent at this gestational interval. Among the gross developmental abnormalities observed in embryos 48h after irradiation, excessive flexion of the embryo and abnormal flexion of the head were the only ones that appeared to be radiation-induced. The mean numerical score (42.3 +/- 0.2, controls; 42.4 +/- 0.1, irradiated) for 17 morphological parameters examined in fetuses at this gestational period compares favorably with other studies. Controls, however, showed greater variability in the extent of development of their forebrain, olfactory system, midbrain, hindbrain, and caudal neural tube. In all cases, there was evidence of slower development in these regions compared to their irradiated counterparts. At term, no significant differences in litter size or resorption rates were observed in irradiated animals compared to the controls, but there was a higher incidence of defective eye development, spinal curvature and visceral anomalies.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8003818 TI - Heterogeneous immunoreactivity of frozen human benign and malignant breast lesions to C-MYC and C-Ha-ras cellular oncogenes. AB - C-myc and c-Ha-ras oncoprotein expression was studied by immunohistochemistry and gene detection by in situ hybridization on serial frozen sections of 32 breast lesions (19 benign biopsies and 13 infiltrating carcinomas). C-myc protein was expressed in 15/19 benign and 12/13 malignant lesions; c-myc gene was detected in 17/19 benign and 13/13 malignant lesions. Although a higher proportion of benign biopsies (8/9) showed more than 50% of protein-positive cells than malignant specimens, this cannot predict the outcome of a lesion. Conversely, p21 ras protein was expressed only in 2/19 benign lesions and in most cases of grade I to III carcinomas. The c-Ha-ras gene was always detected in a small percentage of cells, in both benign and malignant lesions. The results obtained with atypical hyperplasia, a doubtful proliferating lesion, suggests that p21 c-Ha-ras protein expression is not restricted to breast carcinomas. Although Southern blot is commonly considered as a very sensitive technique for oncogene analysis, no amplification of c-myc and c-Ha-ras gene has been demonstrated either in benign or malignant lesions. The detection, on serial frozen sections, of proteins and DNA of c-myc and c-Ha-ras, showed a possible amplification of the c-myc and c-Ha ras genes in various benign and malignant lesions. PMID- 8003819 TI - DNA synthesis in the embryonic chick lens epithelium is arrested after experimental lens rotation. AB - Using autoradiographic technique, we have studied DNA synthesis in normal embryonic chick lens epithelium and after experimental lens rotation. Analysis of the autoradiograms clearly demonstrates that when the lens primordium was rotated 180 degrees, so that lens epithelium was placed facing the interior of the optic cup, the lens epithelial cells completely stop DNA synthesis. This fact suggests that some retinal and vitreal factors are responsible for differentiation and replicative capacity of the lens epithelial cells. PMID- 8003820 TI - Coexistence of serotonin and cholecystokinin in paraneurons of the foetal sheep lung. AB - The coexistence of serotonin and cholecystokinin was studied in foetal sheep lungs at pseudoglandular stage of development by light microscopic immunohistochemistry. The coexistence was examined by staining consecutive sections with the different antibodies. Serotonin and cholecystokinin immunoreactivity was found within consecutive sections of most bronchopulmonary neuroepithelial bodies and in consecutive sections of the same intrapulmonary autonomic ganglia. PMID- 8003821 TI - Acinar cell carcinoma of the pancreas. A histologic, immunocytochemical and ultrastructural study. AB - A rare case of acinar cell carcinoma of the pancreas is presented. Because of its unusual solid growth pattern, correct diagnosis required electron microscopic analysis and the demonstration of intracellular amylase by immunohistochemical stains. The presence of pleomorphic electron-dense cytoplasmic granules containing fibrillary internal structures is confirmed in this ultrastructural study. The differential diagnosis of acinar cell carcinoma from other neoplasms involving the pancreas, including neuroendocrine tumours, poorly-differentiated adenocarcinomas and neoplasms of putative acinar cell derivation, is discussed. PMID- 8003822 TI - Effect of estrogenization in the first day of life on the reproductive system in male rats. AB - The aim of the present report was to investigate dynamics of morphological and functional changes in the reproductive system of male rats between 20th and 84th day of life, injected neonatally with a single dose of stilbestrol. Marked reduction in relative weights of testes and accessory sexual glands was demonstrated in various periods of life. This was associated with inhibition of spermatogenesis at the stage of primary spermatocytes and with morphological as well as functional alterations in epididymis, seminal vesicles and ventral prostate. In the serum, high levels of LH and lowered testosterone levels were demonstrated. PMID- 8003823 TI - Topographic distribution and quantitative analysis of retrograde-labelled cells in the substantia nigra following administration of fluoro gold in the caudate putamen nucleus. AB - The organization of the efferent projections of the substantia nigra following the injection of 0.4 microliters of 2% Fluoro Gold into the caudate-putamen nucleus of rats of both sexes was studied. After a survival period of 72 h, the greatest number of labelled cells was visualized in the substantia nigra, with lower numbers in adjacent structures (ventral tegmental area, zona incerta and medial lemniscus). The cells featured an intensely fluorescent gold-coloured soma and were varied in shape (round or oval); short sinuous projections arose out of them, corresponding to the dendrites and axons of the neurons. In the statistical study, no significant differences were observed between males and females. A similar pattern of distribution was found ranging from the rostral to the caudal regions of the substantia nigra, occupying the whole of the extent of the substantia nigra; this distribution was most predominant in the rostro-caudal transition of the pars compacta of the substantia nigra. PMID- 8003824 TI - A Golgi study on the red nucleus in man. AB - The different cell types comprising the human red nucleus (RN) from eight patients without neuronal diseases were investigated using the Golgi-Braitenberg method for long-stored autopsy material. No giant cells were found due to regression of the magnicellular part of the human RN. We found larger (40-50 microns) and smaller (30 microns perikaryon size) medium-sized multipolar neurons with long dendrites, mushroom spines and typical distal dendritic tufts. The larger medium-sized RN neurons had some brush-shaped dendritic end portions which could not be observed in the Golgi studies on various other mammals described in the literature. We additionally found small neurons with a perikaryon size of 15 microns. These cells were thought to be intrinsic neurons similar to those in animal investigations. The neuronal types found in the normal human RN corresponded to those in the parvicellular part of the mammalian RN. Dendritic end brushes, however, are typical only for the human RN. PMID- 8003825 TI - Ultrastructural and immunocytochemical study of the leptomeres in the mouse cardiac muscle fibre. AB - The three-dimensional configuration and chemical composition of leptomeres in the mouse ventricular cardiac muscle fibre were electron microscopically and immunocytochemically investigated using semithin sections and specific antibodies against actin, the intermediate filament proteins desmin and vimentin, and the actin-binding proteins alpha-actinin, filamin and vinculin. The leptomeres appeared columnar in shape and periodically segmented by electron-dense disc-like septa. The electron-lucent areas between these septa were composed of fine interlinked filaments running obliquely to the major axis of the leptomere. Actin was localized in the electron-dense lines of the leptomeres but not in the fine filaments. No reaction was, however, detected for desmin, vimentin, vinculin, filamin and alpha-actinin. The present results suggest, therefore, that the leptomeres may not have a contractile function. PMID- 8003826 TI - Three-dimensional finite element modeling of a cervical vertebra: an investigation of burst fracture mechanism. AB - Finite element modeling was used to study the mechanical behavior of a cervical vertebra under axial compressive loading. A three-dimensional (3-D) finite element (FE) model of a mid-cervical vertebra using inhomogeneous material properties was generated from quantitative computed tomographic (CT) scan data. This model improved upon previous vertebral FE models by using a highly refined mesh to represent the 3-D variation in material properties of vertebral bone. Traumatic loading of the vertebra was simulated by applying an axial compressive displacement through linear spring elements. Bone strength was computed from the CT scan data and compared with predicted stress. Based on the maximum shear stress theory of failure, the model predicts initiation of failure in the central cancellous region of the vertebral body. The type of fracture pattern predicted by the model is consistent with the typical cervical burst fracture that is seen clinically after compressive loading of the cervical spine. As such, we have developed a tool that can be useful for validating proposed fracture mechanisms in the cervical spine. PMID- 8003827 TI - Pathogenesis of uncus deformation and vertebral artery compression: histologic investigations of the uncus and dynamic angiography of the vertebral artery in the cadaveric cervical spine. AB - Twenty-one cervical spines were collected from fresh cadavers (12 male, nine female), their ages ranging from 10 to 90 years (mean 49.47). After removing muscle debris from the spines, they were mounted and tested on a device to passively reproduce the main movements of the spine. The degree of motion in flexion-extension and lateral bending significantly decreased from group A (ages 10-49 years) to group B (51-90 years) (p < 0.005) and was directly correlated with the amount of cervical spine degenerative alterations. The incidence of these alterations, classified according to Lysell (1969), was highest at C5-6. On the testing machine, dynamic angiography of the vertebral artery showed an impingement with extrinsic compression of the vessels in four of 28 successful injections. The histologic serial sections of the uncus showed a characteristic pattern of ossification-deformation: a newly formed cartilaginous tissue tipping the apex of the uncus, forming a double protruding contour of the apex, rapidly ossifying, and appearing to deform outward together with the disk degeneration and consequently decreasing in height. PMID- 8003828 TI - Failure of synthes anterior cervical fixation device by fracture of Morscher screws: a biomechanical study. AB - Anterior cervical fixation using the Synthes system has become increasingly popular. Two screw types for anchoring the plates include a "solid" titanium expansion screw and a plasma-sprayed fenestrated expansion screw that permits bony ingrowth. These screws were compared clinically and in the laboratory. In our first 20 cases using Synthes plates secured by Morscher fenestrated screws, 3 failures were observed, unilaterally in 1 patient and bilaterally in 2 others. In the unilateral screw failure, the contralateral screw was "solid" and did not fail. In the mechanical studies, screws were secured in the Synthes plate and embedded into methylmethacrylate and subjected to a sinusoidal bending moment to the mid-shaft of the screw. Load deflection data and cycles to failure were recorded. Fenestrated screws were found to demonstrate nearly twice as much deformation at failure and tolerated significantly fewer cycles to failure than did "solid" screws (p < 0.05). Because benefits of bony ingrowth into the screw are not well identified, the risks of fenestrated screw failure should preclude their routine use. PMID- 8003829 TI - Intraosseous screw fixation of anterior cervical graft construct after diskectomy. AB - This article describes a new technique of intraosseous screw fixation of the cervical spine, as well as a retrospective review of 27 patients who had anterior cervical interbody fusion after diskectomy and fixation with one intraosseous Herbert screw, with a minimum follow-up of 1 year. The study included 19 men and eight women. There were no neurologic complications at final follow-up evaluation. All patients had radiographic evidence of fusion. No screw breakage, back-out, or dislodgement occurred. Optimal intraoperative radiographic evaluation for accurate intraosseous screw placement is recommended. The use of intraosseous screw fixation is a useful addition to the armamentarium of the spine surgeon when fixation of anterior cervical graft after diskectomy is required. One hundred percent rate of union and prevention of complications related to the currently used anterior fixation systems are the major advantages of this method. PMID- 8003830 TI - Axes of motion of thoracolumbar burst fractures. AB - The neurological injury associated with thoracolumbar burst fractures may be due to the acute trauma event or due to chronic instability. For functional diagnosis and appropriate treatment, knowledge of the altered motion patterns of burst fractures may be helpful. Thirteen human cadaveric spine specimens were impacted at high speed in axial compression, resulting in 10 clinically relevant burst fractures. The specimens were subjected to a three-dimensional flexibility test (flexion, extension, bilateral lateral bending, and bilateral axial torque) before and after trauma. The vertebral motion across the burst fracture was described in terms of the helical axis of motion (HAM), a set of parameters that concisely and completely describes the three-dimensional motion. The vertebral rotations about the HAM increased significantly with burst fracture in all loading directions: flexion 8.1-17.7 degrees, extension 7.2-12.5 degrees, lateral bending 8.5-20.6 degrees (to one side), and axial torque 3.6-12.6 degrees (to one side). The HAM shifted significantly in a posterior direction with burst fracture in flexion (11-mm shift), extension (15-mm shift), and axial torque (11-mm shift). No other significant shifts in the HAM position were observed. The translation along the HAM and the orientation of the HAM did not change significantly with injury in any of the loading directions. The results provide clinically relevant information regarding the optimal treatment of thoracolumbar burst fractures. Specifically, fixation methods for burst fractures must be particularly stiff in lateral bending and axial rotation, the directions of greatest instability. PMID- 8003832 TI - Cotrel-dubousset instrumentation in thoracolumbar seat belt-type and flexion distraction injuries. AB - For many years, all the internal fixation devices available for the surgical treatment of thoracolumbar fractures [Harrington rods (HR); Luque rods (LR); Hartshill rectangle (HTR); Roy Camille plates (RCP)] were not always able to distribute all the reductive strains (distraction, compression, derotation), or to guarantee solid stabilization without external supports. In some cases (with HR), only distraction forces might be applied, but stability of the assembly was very poor. Otherwise (with LR, HTR, or RCP), stability was well achieved using segmental fixation systems (with SSW, screws), but reduction was possible only by deflecting the spine towards the rods (or plates), by winging the sublaminar wires (or screws). Restoration of normal sagittal alignment was also very difficult to obtain. The use of internal fixation systems for reduction of thoracolumbar fractures when distraction or compression forces are needed are essential for the spinal surgeon and the patient. In some cases of thoracolumbar fractures (seat belt; flexion-distraction), in fact, the use of distraction forces is not suitable, leading only to overdistraction, not to reduction. The introduction of Cotrel-Dubousset instrumentation (CDI) in 1983, and its subsequent use in spinal traumatology, seems to answer all these unresolved questions. PMID- 8003831 TI - Correlations between screw hole preparation, torque of insertion, and pullout strength for spinal screws. AB - The bone-screw interface is critical in the use of spinal instrumentation. The purpose of these experiments described here was twofold. First, to determine whether a correlation existed between torque generated during screw insertion and the pullout strength. Second, to determine how differing surgical methods of screw hole preparation influenced torque of insertion and screw pullout strength. A series of experiments were carried out in which screws were inserted into synthetic bone (experiment 1) and into calf vertebrae (experiment 2). The method of screw hole preparation (i.e., diameter of entrance hole and pilot hole) was varied while the resulting torque of insertion and the pullout strength of the screw was measured in each case. A torque screwdriver was used to measure the torque of insertion of the screws. Screw pullout strength was measured using a materials testing machine. Two important results emerged from these experiments. First, a higher torque of insertion correlated with a higher screw pullout force. This correlation may be useful intraoperatively in evaluating fixation. Second, torque of insertion and pullout force were more influenced by cortex over-drill diameter than pilot hole diameter. These experiments show the importance of the dorsal cortex in pedicle screw fixation. PMID- 8003833 TI - Significance of Gd-DTPA-enhanced magnetic resonance imaging for lumbar disc herniation: the relationship between nerve root enhancement and clinical manifestations. AB - Gd-DTPA-enhanced magnetic resonance (MR) imaging can depict not only the morphology but also the pathological changes of a nerve root compressed by herniated disc. Enhanced MR imaging was performed on 115 patients treated surgically for lumbar disc herniation. Nerve root enhancement was seen in 39.1% of the patients preoperatively and in 58.7% postoperatively. Preoperative root enhancement reflects the radicular pain intensity rather than the degree of neurological deficits, whereas postoperative enhancement did not correlate with the radicular symptoms. Nerve root enhancement represents an intraneural edema in the affected nerve root. Enhanced MR imaging is a potential method for the identification of an affected nerve root in patients with a discrepancy between the level of disc herniation and neurological manifestations. PMID- 8003834 TI - Recurrent lumbar disc herniation: results of repeat laminectomy and discectomy. AB - Forty-six patients who had previously undergone laminectomy and discectomy for lumbar disc herniation were treated for recurrent disc herniation by repeat laminectomy and discectomy. Fifty recurrences were treated in 46 patients, an average of 7 years and 1 month after the previous laminectomy (range 3 months-22 years and 11 months). Thirty-four patients were treated for 37 recurrences at the same level, with three undergoing a third laminectomy and discectomy. Twelve patients were treated for 13 recurrences at a different level. Four patients underwent a third laminectomy and discectomy for recurrent disc herniation. Forty one patients had follow-up of at least 1 year and average follow-up was 4 years and 6 months (range 1 year-10 years and 8 months). There were 28 good (69%), 10 fair (24%), and 3 poor (7%) results. Patients with pending litigation or work related injuries (5 good, 5 fair, and 3 poor) did less well overall than those without these issues (23 good, 5 fair, and 0 poor). Fusion is not routinely required in patients undergoing repeat laminectomy and discectomy for recurrent disc herniation. In the absence of objective evidence of spinal instability, recurrent disc herniation may be adequately treated by repeat lumbar laminectomy and discectomy alone. PMID- 8003835 TI - Passive reduction of spondylolisthesis on the operating room table: a prospective study. AB - Translational motion of low-grade spondylolisthesis is traditionally assessed with lateral flexion and extension radiographs. Maximum motion in an unanesthetized patient may be limited by patient cooperation, pain, or muscle spasm. Twenty-four patients with degenerative or isthmic spondylolisthesis were assessed with preoperative lateral flexion and extension radiographs. A lateral radiograph was obtained on the operating room table after administering an anesthetic, exposing the spine, and performing a laminectomy. The percentage slip decreased from 24 to 15 to 6% on flexion, extension, and intraoperative lateral radiographs, respectively (p < 0.001). The amount of reduction did not correlate with disc height, slip angle, slip level, or type of spondylolisthesis. Many low grade spondylolisthesis deformities reduce almost completely on the operating table. Translational motion of spondylolisthesis is greater than preoperative flexion and extension radiographs indicate. PMID- 8003836 TI - Pyogenic vertebral osteomyelitis: treatment by anterior spinal debridement and fusion. AB - Forty-three patients with pathologically proven vertebral osteomyelitis were studied between 1957 and 1990. Thirty-nine underwent anterior debridement and fusion, and four underwent anterior debridement only. The indications for surgery were uncertain diagnosis, persistent pain, failed conservative treatment with uncontrolled sepsis, and neurological involvement. Thirty patients were followed up for an average period of 5 years, with a minimum of 2 years and the longest for 15 years. All their symptoms improved after surgery; only one patient subsequently deteriorated due to multiple level recurrence. All patients with neurological deficit improved. Bony fusion occurred in 93% of cases (average time to fusion, 6.8 months), and 90% of the patients were able to return to their original work 4-20 months after surgery. We feel that anterior debridement and spinal fusion allow for reliable microbiological and histological diagnosis, and rapid relief of symptoms and return to work. Primary bone grafting is successful despite the presence of infection. PMID- 8003837 TI - Automated percutaneous discectomy for reherniations of lumbar discs. AB - Ten patients with lumbar disc reherniation at the same level as the one previously openly operated on were treated by automated percutaneous discectomy (APD). The results after follow-up for 2.5 years, on the average, showed 70% with complete or significant pain relief, 60% with motor deficit improvement, and 22% with improvement of sensory deficit. Included among the patients who had pain relief were two of three in whom discography had produced only a small amount of pain, but only one of two in whom the contrast material showed contained epidural leak. To reduce the unsuccessful results, patients with segmental instability or spinal stenosis after open surgery should not be treated by APD. PMID- 8003838 TI - Kinematics of the cervical spine canal: changes with sagittal plane loads. AB - Spondylotic myelopathy is a result of decreased spinal canal space due to degeneration. The space also may change with physiological movements. The knowledge of the normal physiological changes is necessary for a better understanding of the clinical symptoms. Using a novel technique, we measured the changes in disk bulge, ligamentum flavum bulge, and anteroposterior canal diameter in response to tension-compression forces (up to 40 N each) and combined loading: 2 Nm of flexion or extension moment combined with 20 N compression force in five human cadaveric lower cervical spine specimens (C4-C7). From tension to compression, the average disk bulge changed 1.13 mm or 10.1% of the original canal diameter. The ligamentum flavum bulge changed 0.73 mm or 6.5% of the canal diameter. From flexion to extension the average disk bulb changed 1.16 mm or 10.8% of the canal diameter, whereas the ligamentum flavum bulge changed 2.68 mm or 24.3% of the canal diameter. Most of the changes in the bulges occurred with a small load application around the neutral position of the spine. The results of this study demonstrate that ligamentum flavum bulge can contribute significantly to canal encroachment in extension and that a flexed posture increases the sagittal diameter of the spinal canal. PMID- 8003839 TI - Tooth loss and skeletal bone density in healthy postmenopausal women. AB - Associations between dental status and skeletal bone density were investigated in a group of 329 healthy postmenopausal women with normal bone density. Bone mineral density (BMD) of the lumbar spine, femoral neck and distal radius were measured by dual- or single-photon absorptiometry. Number of teeth remaining were counted and presence of complete dentures noted by a nurse practitioner. Forty eight women (15%) wore a complete maxillary and/or mandibular denture: 22(7%) were completely edentulous and an additional 26 (8%) had one edentulous ridge. Among women without complete dentures (n = 281), significant positive linear relationships were observed between number of teeth and BMD at the spine (p < 0.05) and radius (p < 0.01), controlling for years since menopause, pack-years of smoking, education and body mass index. BMD did not differ between the groups with and without dentures. However, women who acquired dentures after the age of 40 years had significantly lower mean spinal and radial BMD than women who acquired dentures at age 40 years or earlier (at the radius, 0.584 +/- 0.015 v 0.630 +/- 0.017 g/cm2, p < 0.05; at the spine, 1.043 +/- 0.031 v 1.124 +/- 0.029 g/cm2, p = 0.05). In linear regression analysis, significant independent correlations were found among all women (n = 329) between number of teeth and age (partial r = -0.19, p < 0.001), pack-years of cigarette use (partial r = -0.23, p < 0.001) and years of education (partial r = +0.11, p < 0.05). These associations between dental status and BMD support the hypothesis that systemic bone loss may contribute to tooth loss. PMID- 8003841 TI - The assessment of vertebral deformity. PMID- 8003840 TI - Dual-energy X-ray absorptiometry of the spine in anteroposterior and lateral projections. AB - Dual-energy X-ray absorptiometry (DXA) of the lumbar spine provides an estimation of the bone mineral content (BMC) corrected by the projected area of the spine and expressed in g/cm2. This two-dimensional estimate of the bone mineral density (BMD) is influenced by the skeletal size, assessed by the subject's height. In order to obtain an estimate of the volumetric BMD, we measured BMC with a new DXA device (Sophos L-XRA) equipped with 24 detectors and a rotating arm, thus allowing scanning of the lumbar spine in both an anteroposterior (AP) projection and a lateral (LAT) projection with the patient in a supine position. Comparison between the results obtained on the third (L3) and fourth (L4) lumbar vertebrae with automatic or manual analysis showed that the best precision was obtained with the lateral measurement of L3 alone with an automatic soft tissue baseline determination. Results were expressed in g/cm2 and in g/cm3 (by dividing the g/cm2 value by the width (AP area divided by the height of the vertebra) of L3), and were compared with those obtained by conventional AP scanning of L2-4 (g/cm2). The in vivo precision error evaluated by triplicate measurements on 10 controls was 17 mg/cm2 (1.96%) and 5.2 mg/cm3 (2.31%) for LAT L3 as compared with 13 mg/cm2 (1.15%) for AP L2-4. Volumetric BMD (g/cm3) measurement, assessed in vitro on a calibrated hydroxyapatite phantom, and the absolute values obtained in normal women were similar to those obtained by quantitative computed tomography (QCT).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8003842 TI - Distribution of bone mineral density in the lumbar spine in health and osteoporosis. AB - The significance of variability in bone mineral density (BMD) between lumbar vertebrae L1 to L4 in the same individual was investigated by dual-energy X-ray absorptiometry in 1000 normal women aged 40-60 years (average 52 years) and 145 women aged 45-80 years (average 65 years) with vertebral osteoporosis. The mean BMD increased from L1 to L4 in normal women from 0.841 g/cm2 to 1.017 g/cm2, and in osteoporotics from 0.562 g/cm2 to 0.709 g/cm2. Z scores for osteoporotic women (Z = osteoporotic BMD - age-normal BMD/normal SD) were significantly lower for individual vertebrae compared with L1-4 and at L4 compared with L1, L2 and L3 (p < 0.001). The mean difference between Z scores for the highest and lowest vertebrae in an individual was 0.70 for normals (SD = 0.40) and 0.64 for osteoporotics (SD = 0.36). The mean Z score difference between the L1-4 Z score and the lowest individual vertebral Z score was 0.36 for normals (SD = 0.23) and 0.06 for osteoporotics (SD = 0.31). However, receiver operating analysis (ROC) curves showed that the lowest Z score for any individual vertebra did not provide improved discrimination between normals and osteoporotics when compared with the L1-4 Z score. The area under the ROC curve for L1-4 was significantly greater than for individual vertebrae (p < 0.05) and that for L4 was significantly smaller than for L1, L2 or L3 (p < 0.001). In conclusion, L1-4 BMD gives greater diagnostic sensitivity for osteoporosis than individual vertebrae, and L1, L2 and L3 are better than L4.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8003843 TI - Increase in femoral bone density in young women following high-impact exercise. AB - Healthy premenopausal women were randomized into control and test groups; both exercised weekly in class and daily at home for a year. The test class did intermittent high-impact exercise; the control class did low-impact exercise. Bone density was assessed blind using dual energy X-ray absorptiometry at the femur (neck, Ward's triangle and trochanter) and at the lumbar spine (antero posterior L1-4) on entry into the study, and again after 6 months (n = 27) and 12 months (n = 19). At 6 months the test group (n = 14) showed a significant increase of 3.4% in trochanteric bone density (p = 0.01) and this was significantly different from control (p = 0.05). In the second 6 months the control group was crossed over to high-impact exercise and showed a significant increase of 4.1% in trochanteric density (n = 7) while the original group maintained their improvement relative to baseline. PMID- 8003844 TI - Two years' effectiveness of intravenous pamidronate (APD) versus oral fluoride for osteoporosis occurring in the postmenopause. AB - Bisphosphonates seem to be effective as antiresorptive agents in the prevention and treatment of osteoporosis. However, the optimal dose and route of administration as well as the specific effects on cortical or trabecular bone have not been clarified. To compare pamidronate (APD) with fluoride (F) in the therapy of postmenopausal osteoporosis, 32 osteoporotic women were treated for 2 years either with APD (30 mg as a single intravenous infusion over 1 h every 3 months, n = 16, mean age 65 years) or with fluoride orally (20-30 mg F/day, n = 16, mean age 67 years) in an open study. Both groups received 1 g calcium and 1000 U vitamin D per day, but no estrogens or other drugs acting on bone. Both groups showed the same initial mean number of fractures per patient (2.8 and 2.7). Bone densitometry was performed every 6 months at three sites: lumbar spine and hip with dual-energy X-ray absorptiometry (BMD), distal forearm with single photon absorptiometry and lumbar spine with quantitative computed tomography. Biochemical assessment was performed in blood and urine every 3 months. Lumbar BMD (g/cm2, mean +/- SEM) increased from 0.632 (+/- 0.030) at time 0 to 0.696 (+/ 0.028) at 24 months in the APD group (p < 0.001), and from 0.684 (+/- 0.025) to 0.769 (+/- 0.028) in the fluoride group (p < 0.001). Femoral neck BMD increased significantly from 0.558 (+/- 0.025) to 0.585 (+/- 0.025) (p < 0.01) in the APD group, whereas it did not change in the fluoride group.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8003845 TI - Dehydroepiandrosterone sulphate and bone mineral density. AB - Several series of data suggest that alterations in adrenal androgen output might be a contributing factor to changes in bone mass. To study the possible relationship between bone density and serum levels of dehydroepiandrosterone sulphate (DHEAS) we investigated 105 women (aged 45-69 years; 76 postmenopausal, 29 perimenopausal). The patients were divided into two groups according to the bone mineral density (BMD) measurement (normal density n = 50, low density n = 55). BMD was measured by dual-energy X-ray absorptiometry of the lumbar spine and femoral neck. Bone mineral content (BMC) of the radius midshaft was measured by single photon absorptiometry. Serum DHEAS level was significantly lower in the 'low density' group than in the 'normal' one (1.91 +/- 1.04 v 4.77 +/- 2.03 mumol/l, p < 0.001). The serum DHEAS level decreased significantly with age in both groups (r = 0.43, p < 0.001 in the 'normal' group; r = 0.35, p < 0.01 in the 'low density' group). Unlike the slopes, the positions of the regression lines differed significantly (difference 2.85 mumol/l, p < 0.001). Correcting for age by multiple linear regression we established a significant positive relationship between DHEAS and BMD of the lumbar spine and femoral neck, and BMC of radius midshaft as well. Since there was no significant difference between the two groups regarding oestrogens, we suggest that DHEAS may have a non-oestrogenic effect on bone. The odds ratio of a subject with a low (< 3.3 mumol/l) serum DHEAS level having low BMD was 40 (confidence interval 13-126).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8003846 TI - The sequelae of vertebral crush fractures in men. AB - The number of osteoporotic fractures is rising in men and women, because of the demographic trend towards an aging population and an increase in the age-specific incidence of fractures. Although previous studies have examined the morbidity following hip fractures in women, there is little information on the sequelae of vertebral crush fractures in men. We have therefore collected data on loss of height, kyphosis, peripheral fractures and functional status in 63 men with symptomatic vertebral fractures. Loss of height was documented in 49% of the men, while kyphosis was present in 54%. A past history of 50 non-vertebral fractures was obtained in 27 patients (43%), involving the ribs (17), lower arm (13) and femoral neck (4). Each patient then completed the Nottingham Health Profile (NHP), which gives information on perceived health. Men with vertebral crush fractures had higher scores for all six domains of the NHP when compared with age matched and more elderly control subjects, implying greater morbidity. This was particularly marked for the energy, pain and mobility domains of the NHP. We conclude that there is considerable morbidity associated with vertebral crush fractures in men, which should be assessed in any trial of therapeutic intervention. This study suggests that the NHP may be a useful instrument in this regard. PMID- 8003847 TI - The effect of previous oral contraceptive use on bone mineral density in perimenopausal women. AB - The bone mineral density (BMD) of the lumbar vertebrae L2-4 and femoral neck was determined by dual-energy X-ray absorptiometry (DXA) in 3222 perimenopausal women a random stratified sample of the population-based Kuopio Osteoporosis Study (OSTPRE). The mean age of the women was 53.4 years (range 47.9-59.6 years). Twenty-nine percent of the women were past users of oral contraceptives (OC) containing 50 micrograms or less of ethinyl estradiol and 7.4% (n = 250) of the women reported OC use for more than 6 years. There was a slight but statistically significant difference between OC users (n = 939) and non-users (n = 2283) in lumbar BMD (1.134 +/- 0.155 g/cm2 v 1.123 +/- 0.161 g/cm2, p = 0.014). A statistically significant difference was recorded also after adjustment for years since menopause, duration of hormonal replacement therapy (HRT) and present weight (p = 0.044). When the analysis was performed among women who had never used oestrogen replacement therapy (n = 1427) and among premenopausal women (n = 387), no differences in BMD were found between OC users and non-users. Similarly, femoral neck BMD did not differ between the groups. This population-based study demonstrated a slightly higher lumbar BMD among past OC users. However, OC users and non-users differed from each other in many behavioral characteristics. Thus, the differences in BMD may be accounted for more by other factors than by past OC use itself. The low-dosage estrogen OCs used today would not be expected to have any positive bone effects among future perimenopausal women. PMID- 8003848 TI - Bone mineral density in young women with long-standing amenorrhea: limited effect of hormone replacement therapy with ethinylestradiol and desogestrel. AB - To assess bone mineral density (BMD) at different skeletal sites in women with hypothalamic or ovarian amenorrhea and the effect of estrogen-gestagen substitution on BMD we compared BMD of 21 amenorrheic patients with hypothalamic or ovarian amenorrhea with that of a control population of 123 healthy women. All amenorrheic patients were recruited from the outpatient clinic of the Division of Gynecological Endocrinology at the University of Berne, a public University Hospital. One hundred and twenty-three healthy, regularly menstruating women recruited in the Berne area served as a control group. BMD was measured using dual-energy X-ray absorptiometry (DXA). At each site where it was measured, mean BMD was lower in the amenorrheic group than in the control group. Compared with the control group, average BMD in the amenorrheic group was 85% at lumbar spine (p < 0.0001), 92% at femoral neck (p < 0.02), 90% at Ward's triangle (p < 0.03), 92% at tibial diaphysis (p < 0.0001) and 92% at tibial epiphysis (p < 0.03). Fifteen amenorrheic women received estrogen-gestagen replacement therapy (0.03 mg ethinylestradiol and 0.15 mg desogestrel daily for 21 days per month), bone densitometry being repeated within 12-24 months. An annual increase in BMD of 0.2% to 2.9% was noted at all measured sites, the level of significance being reached at the lumbar spine (p < 0.0012) and Ward's triangle (p < 0.033). In conclusion BMD is lower in amenorrheic young women than in a population of normally menstruating, age-matched women in both mainly trabecular (lumbar spine, Ward's triangle, tibial epiphysis) and mainly cortical bone (femoral neck, tibial diaphysis).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8003849 TI - Inhibitors of cyclic nucleotide phosphodiesterase isoenzymes--their potential utility in the therapy of asthma. PMID- 8003850 TI - Respiratory tract eicosanoid measurement using microdialysis sampling and GC/MS detection. AB - Eicosanoids are important mediators in many physiological and pathophysiological conditions. Sampling the eicosanoids remains a challenge, particularly in the respiratory tract. We examined the possibility that microdialysis might offer a means for sampling the large airways which would provide profiles of local eicosanoid levels before and after challenge. Guinea-pigs were anesthetized by ip injection of urethane and a tracheotomy performed. Microdialysis probes were inserted 2 cm into the tracheal opening, and samples were collected for 1 h intervals over 5 h. Injections of arachidonic acid, leukotriene (LT) D4, or saline vehicle were made iv at the beginning of the third hour. Prostaglandins (PG) E2, D2, F2 alpha and 6-keto-F1 alpha and thromboxane (TX) B2 were determined by GC/MS. Significant post-treatment increases in levels were observed following the injection of arachidonic acid for all eicosanoids except 6-keto-PGF1 alpha. The greatest change was an 8.1-fold increase for PGD2 (P < 0.025) while the smallest change was a 3.5-fold increase for TXB2 (P < 0.025). Intravenous administration of LTD4 caused significant increases in levels of PGE2 (P < 0.025), PGF2 alpha (P < 0.05) and 6-keto-PGF1 alpha (P < 0.025) in the first hour after challenge. No increase was observed in control experiments following saline injection. These results indicate that microdialysis provides a useful methodology for sampling local eicosanoid production. PMID- 8003851 TI - Effects of a corticosteroid, budesonide, on alveolar macrophage and blood monocyte secretion of cytokines: differential sensitivity of GM-CSF, IL-1 beta, and IL-6. AB - Down-regulation of cytokine production in activated human blood monocytes (BMs) and alveolar macrophages (AMs) can be achieved in vitro by treatment with corticosteroids. The inhibition of cytokine secretion by corticosteroids may have important therapeutic consequences in e.g. asthma. However, relatively little is known about possible differences in the sensitivity of different cytokines to corticosteroid treatment. Homologous BMs and AMs were obtained from six healthy volunteers. Secretion of interleukin-1 beta (IL-1 beta), interleukin-6 (IL-6) and granulocyte-macrophage colony-stimulating factor (GM-CSF) in the cultures of lipopolysaccharide (LPS) stimulated adherent BMs and AMs was analysed using specific immunoassays. Sensitivity of the IL-1 beta, IL-6, and GM-CSF secretion to the in vitro treatment with a synthetic corticosteroid, budesonide, was compared. BMs and AMs displayed significant differences in both cytokine secretion and susceptibility to regulation by budesonide. When added to the BM cultures concomitantly with LPS, budesonide suppressed IL-1 beta and IL-6 only partially (to 30% of the control level). In contrast, GM-CSF release in these cultures was almost totally inhibited by budesonide (> or = 10(-8) M). The IC50 for inhibition of the GM-CSF secretion was as low as 2 x 10(-10) M. In the AM cultures, budesonide had very little effect on IL-1 beta and IL-6 secretion (inhibition to 80% and 60% of control levels, respectively), while GM-CSF secretion was suppressed to 20% of control by budesonide concentrations > or = 10(-7) M.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8003852 TI - Leukotriene D4 receptor antagonism reduces airway hyperresponsiveness in monkeys. AB - Airway hyperresponsiveness (AHR) and pulmonary inflammation are observations that are consistently associated with asthma and also occur in a well-characterized monkey model of asthma. The following study was performed to determine whether treatment with an LTD4 receptor antagonist, ICI 198,615, could attenuate antigen induced pulmonary inflammation and AHR in monkeys using the following protocol. On day 0, the PC200 (the concentration of methacholine (MCh) that doubled respiratory system resistance, Rrs) was determined in 6 male, atopic, cynomolgus monkeys, previously characterized in historical control trials (Control #1) as airway hyperresponsive. Bronchoalveolar lavage (BAL) was then performed to determine total and differential leukocyte counts. On days 3, 5 and 7, each monkey received 10 mg/kg ICI 198,615 (im) 30 min prior to Ascaris suum (Ag) aerosol exposures which doubled Rrs. On day 10, the post-Ag PC200 to MCh was determined and BAL was repeated. Five weeks after this trial was complete, a bracketing control trial (Control #2) was performed in which the monkeys were administered vehicle prior to each Ag exposure. In comparison to the response in both control trials, treatment with the LTD4 antagonist significantly (P < 0.05) inhibited the development of AHR and also significantly reduced (P < 0.05) peripheral blood lymphocyte counts after Ag challenge. Treatment with ICI 198,615 reduced the Ag-induced increase in BAL eosinophils, but statistical significance was obtained only when treated animals were compared to Control #1, not Control #2.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8003853 TI - The protective effects of ipratropium bromide and terbutaline on distilled water induced bronchoconstriction. AB - In a randomized, double-blind, placebo-controlled study, we investigated the protective effects of ipratropium bromide 160 micrograms and 320 micrograms and terbutaline 500 micrograms on ultrasonically nebulized distilled water (UNDW) induced bronchoconstriction in nine stable asthmatic patients. Both drugs caused a significant increase (P < 0.001) in baseline FEV1 with no significant differences between the drugs or both doses of ipratropium bromide. Pre inhalation of ipratropium bromide 320 micrograms and terbutaline 500 micrograms inhibited UNDW-induced bronchoconstriction (P < 0.01), whereas ipratropium bromide 160 micrograms had no protective effect. The protective effects of ipratropium bromide showed a large interindividual variation. There was no correlation between the increase in baseline FEV1 and PD20 UNDW, indicating that the protective effect on UNDW-induced bronchoconstriction is not dependent on the bronchodilation induced by terbutaline and ipratropium bromide. It also appears that the UNDW-induced bronchoconstriction is at least partly vagally mediated. PMID- 8003854 TI - The use of the sterile connecting device in transfusion medicine. PMID- 8003855 TI - Neonatal alloimmune thrombocytopenia. PMID- 8003856 TI - The collection of platelets by apheresis procedures. AB - Collection of platelets by apheresis has been a major advance in transfusion medicine. It has allowed the supply of a therapeutically beneficial component to grow with medical needs. Donors find fulfillment in more frequent donations than are possible with whole blood and know that their donation fills a special need. New technology allows leukocyte reduction in the collection of the component with or without the use of filtration. Matching for refractory patients is possible. However, platelets collected by apheresis have not been shown to be hemostatically different from platelets separated from whole blood donations, and thus, do not represent an advance in therapeutic efficacy. The use of apheresis platelets does reduce donor exposure, but this has not been shown to be a safety advance, although it seems intuitively obvious that transfusion risk is statistically reduced in some patients requiring only a few platelet transfusions. Support of patients by apheresis platelets may or may not reduce the risk of alloimmunization. Apheresis platelets from some equipment have less white blood cell contamination even in the absence of filtration, which may be an advantage. Apheresis platelets could be a major step in the ultimate customization of blood collection, in which some donors would preferentially donate red blood cells, whereas others would donate platelets or plasma depending on their blood type and ability to donate frequently, and the current medical need of their donation. Perhaps this would be the most significant advance from the medical progress initiated by Cohn almost 50 years ago. PMID- 8003857 TI - Quality assurance, or the need for standards, audit systems, and accreditation mechanisms in transfusion medicine. PMID- 8003858 TI - Cellular adhesion molecules. PMID- 8003859 TI - The risk of varicella-zoster infections in different patient populations: a critical review. PMID- 8003861 TI - Chronic esophagitis and subsequent morphological changes of the esophageal mucosa in Barrett's esophagus: a histological study of esophagectomy specimens. AB - Chronic esophagitis and the subsequent morphological changes of the esophageal mucosa were histologically studied in esophagectomy specimens from 15 patients with Barrett's esophagus. Basal layer hyperplasia with papillary elongation, intraepithelial eosinophils, and intraepithelial neutrophils were found in the squamous epithelium of all (100%), 7 (46.7%), and 14 (93.3%) of the 15 specimens, respectively. Moreover, a specialized type of Barrett's mucosa was found in the metaplastic columnar lining of all the specimens. The muscularis mucosae appeared intact beneath the squamous epithelium lining the proximal esophagus in 13 specimens (86.7%), while it became thick and "dual" beneath the metaplastic columnar epithelium lining the distal esophagus in 14 specimens (93.3%). This dual muscularis mucosae, as well as the metaplastic columnar epithelium, particularly the specialized type, may be part of the specific histological changes characteristic of Barrett's esophagus. PMID- 8003860 TI - The role of tumor necrosis factor receptors in cell signaling and the significance of soluble form levels in the serum. AB - Two types of tumor necrosis factor membrane receptors (TNF-R) have been identified, namely 55 and 75 kDa TNF-R. Soluble forms of these receptors are present in the human serum. Recent findings on the role of these two TNF-R in biological cell signaling and the clinical significance of the serum levels of soluble TNF-R (sTNF-R) were reviewed. It is not the uptake of TNF molecules into cells but rather the molecular capping of TNF-R on the cell membrane that initiates the biological activity of TNF. The 55 kDa TNF-R mediates major bioactivities of TNF, while the significance of 75 kDa TNF-R remains unclear. We herein suggest a new concept of the role of these two TNF-R: The 75 kDa TNF-R signal appeared to enhance that of 55 kDa TNF-R in the induction of ICAM-1 expression on HL-60 human promyelocytic leukemic cells. High serum levels of sTNF R are reported in patients with malignancy, endotoxin shock, pneumonia, and autoimmune diseases. However, the source of elevated serum sTNF-R remains unclear. Studies on the clinical usefulness of serum sTNF-R levels as cancer and inflammation markers are now being carried out. PMID- 8003862 TI - Five-year results of a randomized clinical trial comparing modified radical mastectomy and extended radical mastectomy for stage II breast cancer. AB - A controlled cooperative study was carried out to assess the value of modified radical mastectomy for patients with stage II breast cancer. The data was analyzed from 11 institutions in the Shikoku District participating in a prospective clinical trial in which patients were randomly assigned either to a modified radical mastectomy group or an extended radical mastectomy group. These two groups of patients were similar to each other in terms of such background factors as age distribution, menopausal status, TNM classification, tumor size, location of the primary tumor, axillary nodal involvement, histological type, and estrogen receptor status. The median follow-up times in the modified and extended radical mastectomy groups were 4.7 and 4.5 years, respectively. The cumulative curves indicated no difference between the two groups in either disease-free survival or overall survival. The survival rates were classified according to the presence or absence of axillary nodal metastases. However, no significant difference was found between the two groups. These findings thus suggest that the routine removal of the grossly uninvolved major pectoral muscle and parasternal lymph nodes is not necessary in patients with stage II breast cancer. PMID- 8003863 TI - The expression of parathyroid hormone-related protein in human breast cancer with skeletal metastases. AB - The relationship between the expression of parathyroid hormone-related protein (PTHrP) by breast cancer and skeletal metastases, was investigated using a monoclonal antibody against human PTHrP (4B3). The immunohistochemical localization of PTHrP was studied in sections of formalin-fixed, paraffin embedded tissues from 28 breast cancers obtained surgically between 1980 and 1985. Of the 28 patients, 12 developed skeletal metastases, 8 developed lung metastases, and the other 8 were alive and disease-free at the time of this study. Sixteen of the 28 (57%) tumors showed positive immunoreactivity to 4B3, the PTHrP positive ratio being 83% in the patients who developed skeletal metastases, 38% in those who developed lung metastases, and 38% in those without recurrence, respectively. Thus, a significantly higher proportion of the patients who developed skeletal metastases were positive for PTHrP than the other two groups (P < 0.05). Furthermore, the level of positive staining was strongly related to positivity for estrogen and progesterone receptors (P < 0.01). These results are consistent with the hypothesis that PTHrP might be necessary for metastases to erode bone and grow in skeletal sites, and its expression could be related to certain hormones. PMID- 8003865 TI - Gallbladder expansion induced by feeding. AB - By using ultrasound we were able to observe any increase in the size of human gallbladders during feeding. In 91 of 123 cases (74%), the gallbladder expanded for a short time prior to contraction during feeding. The examination on eight patients after gastrectomy and seven patients after a medically induced vagotomy revealed contraction only in response to feeding. In seven normal adults, 200 ml of air injected rapidly into stomach through a gastric tube was seen to induce gallbladder expansion. These results suggest that the gallbladder expands in response to feeding via a cholinergic vago-vagal reflex. PMID- 8003864 TI - Pseudomembranous enterocolitis and hemorrhagic necrotizing enterocolitis in Hirschsprung's disease. AB - From 1977 to 1991, we encountered 67 patients with Hirschsprung's disease and 14 of them developed enterocolitis, with 3 cases being fatal. Enterocolitis occurred preoperatively in 12 infants, as well as after ileostomy in one and after a pull through procedure in another. Seven infants had severe enterocolitis, including three with pseudomembranous enterocolitis and four with hemorrhagic necrotizing enterocolitis. Enterocolitis in Hirschsprung's disease mainly occurs due to intestinal obstruction and ischemia; however, in some cases, Clostridium difficile overgrowth and its toxin also appears to be related to severe pseudomembranous enterocolitis. In severe enterocolitis, antibiotics and enterostomy often prove to be ineffective, and thus an early resection of the affected bowel appears to be necessary. Moreover, when the aganglionic segment extends to the small bowel, severe enterocolitis tends to occur in the aganglionic intestine even after performing an enterostomy, and a resection of the aganglionic bowel is therefore recommended to allow for adequate lavage of the segment distal to the enterostomy site. PMID- 8003866 TI - Pancreatic resection for periampullary carcinoma in the elderly. AB - The effect of pancreatic resection for periampullary carcinoma in the elderly was studied by comparing the pre- and perioperative factors affecting survival in 102 patients less than 70 years of age (group A) with those in 28 patients 70 years and older (group B). Concomitant cardiac and pulmonary diseases were significantly more frequent in group B (P < 0.05), but the difference in routine laboratory data was not significant. The overall operative mortality was 7% (7/102) in group A and 18% (5/28) in group B, while the actuarial 5-year survival rates were 31% in group A and 23% in group B, these differences not being significant. A multivariate analysis using a logistic model showed that blood loss was the greatest risk factor for early postoperative death in the elderly patients, whereas anastomotic dehiscence and postoperative bleeding were significant factors in the younger patients. Thus, we conclude that age is not a contraindication to pancreaticoduodenectomy which offers the only hope for long term survival in patients with periampullary carcinoma; however, meticulous dissection to minimize blood loss is especially important in elderly patients. PMID- 8003867 TI - The inhibitory effect caused by suramin on the paracrine growth of human cancer cells and fibroblasts. AB - The growth interactions between human cancer cells and primary cultured human fibroblasts, and the effects of suramin on them, were investigated using a double chamber technique combined with a 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H tetrazolium bromide (MTT) assay. Human fibroblasts obtained from various organs resected surgically were cultured in a monolayer and used after the third or fourth passage. In the double-chamber assay, the growth of cancer cells in the top chamber was significantly stimulated by some types of fibroblasts in the bottom chamber in a fibroblast density-dependent manner. Interestingly, the growth of cancer cells was stimulated at 140%-147% by fibroblasts obtained from an organ where cancer cells had developed, the MCF-7 versus mammary fibroblasts, and in LS-180 versus colonic fibroblasts, but not by their fibroblast-conditioned medium. Suramin completely inhibited the growth-enhancing interaction between MCF 7 and mammary fibroblasts, and between SH-101 and lung fibroblasts at a clinical concentration of from 50 micrograms/ml to 300 micrograms/ml. It also reduced the growth of LS-180 co-cultured with colon-fibroblasts, but the inhibitory effect was incomplete. These results suggest that mutual growth reliance exists between human cancer cells and primary cultured fibroblasts by diffusible factors secreted by both cells, and that these enhancing effects are related in part to the growth and metastasis of cancer cells in vivo. Suramin was found to have an inhibitory effect on their interaction at a clinically achievable concentration in vitro. PMID- 8003868 TI - The addition of glutathione (YM737) to a crystalloid cardioplegic solution enhances myocardial protection. AB - The effectiveness of a glutathione preparation, YM737, as a free radical scavenger when added to hypothermic (4 degrees C) crystalloid cardioplegic solution was evaluated in this study. Rabbit hearts were preserved for 3 h in cardioplegic arrest by infusing 20 ml crystalloid cardioplegic solution initially, with additional 10-ml boluses administered every 30 min, while maintaining a myocardial temperature of 10 degrees C. They were then reperfused with Krebs-Henseleit bicarbonate buffer at 37 degrees C in a perfusion circuit for 60 min. The hearts were divided into two groups of six: One in which crystalloid cardioplegic solution was perfused (group 1); and one in which crystalloid cardioplegic solution containing YM737 1 mg/ml was perfused (group 2). The postischemic developed pressure (mmHg) in group 2 was significantly greater than that in group 1 after 60 min of reperfusion, being 44.8 +/- 8.4 versus 87.8 +/- 5.2 in groups 1 and 2, respectively (P < 0.01). Moreover, group 2 exhibited significantly lower postischemic left ventricular compliance after 60 min than group 1 (P < 0.01) and a significantly higher postischemic peak LV dp/dt (mmHg/sec) after 60 min of reperfusion, being 925 +/- 213 versus 1,550 +/- 111 in groups 1 and 2, respectively (P < 0.05). Based on the comparisons of postischemic hemodynamics it was concluded that the addition of glutathione to crystalloid cardioplegic solution does in fact enhance myocardial protection. PMID- 8003870 TI - Primary mesenteric tumor of adult T-cell leukemia/lymphoma: report of a case. AB - A rare case of primary mesenteric tumor of adult T-cell leukemia/lymphoma (ATLL) is reported. A 64-year-old man was admitted to our hospital after the diagnosis of a palpable ileocecal tumor. Although the serologic test for human T-cell lymphotrophic virus type I (HTLV-I) antibody was positive, neither ATLL cells in the peripheral blood nor systemic lymphadenopathy were observed. At laparotomy, the tumor was histopathologically revealed to be ATLL, and was also found to be restricted to the mesentery. An immunohistochemical examination of the tumor tissue using a specific monoclonal antibody was positive for CD2 and CD4, and negative for CD8. Proviral genome integration in the tumor cells was found by Southern blotting using a 32P-labeled HTLV-I probe with EcoRI and PstI digestion. Combination chemotherapy including cyclophosphamide, Adriamycin, vincristine, and prednisolone was begun postoperatively, but the patient did not respond to therapy. Up to now, only two cases of ATLL originating primarily in the abdominal cavity have been reported. These cases all demonstrate the need to consider the possibility of a primary ATLL mesenteric tumor without leukemic manifestation in the peripheral blood. PMID- 8003869 TI - A ruptured thymic branch aneurysm mimicking a ruptured aortic aneurysm, with associated bronchial artery aneurysms: report of a case. AB - A 57-year-old woman who went into shock following an acute left hemothorax was operated on after stabilization under the diagnosis of a ruptured aortic aneurysm. A left fifth intercostal thoracotomy was done which revealed approximately 500 ml of bloody effusion in the extrapleural space and 2,000 g of clotted blood in the pleural cavity. While the aneurysm was initially thought to have originated in the isthmic or descending aorta, intraoperative findings revealed a swollen hematomatous thymus adherent to the aorta. A ruptured thymic branch aneurysm, 3 cm in diameter, was subsequently found in the resected hematomatous thymus. Histological examination also revealed several small aneurysms in the tortured bronchial arteries. Postoperative angiography showed a saccular aneurysm, 1.5 cm in diameter, and several smaller aneurysms in the bronchial artery of the left lung. The aneurysm was successfully treated by a transcatheter arterial embolization, and the patient has had no further symptoms since then. To our knowledge, there has been no other case of a ruptured thymic artery aneurysm reported in the literature, and only a few cases of bronchial artery aneurysms have been documented. PMID- 8003871 TI - Hepatocellular carcinoma with a solitary adrenal metastasis and poor hepatic functional reserve: report of a case. AB - A 54-year-old man with a 15-year history of liver disease, was found by his family physician to have multiple tumors in the right lobe of the liver and a large right retroperitoneal tumor. He was referred and admitted to our institute where a preoperative diagnosis of liver cirrhosis complicated by hepatocellular carcinoma and probable right adrenal metastasis was made. Because his hepatic functional reserve was so poor, only resection of the right adrenal tumor with a splenectomy for hypersplenism and a cholecystectomy for the prevention of cholecystitis secondary to the scheduled transcatheter arterial embolization was performed. The patient was discharged in good clinical condition 5 weeks after surgery. PMID- 8003872 TI - Bilateral giant bullae with rapidly increasing fluid in the right bulla following operation: report of a case. AB - A 33-year-old Japanese male was admitted to our hospital for the treatment of left pneumothorax. He was found to have bilateral giant bullae. Retention of fluid was observed in the right giant bulla. The fluid accumulated rapidly directly after bullectomy and excision of the left giant bullae. This suggested the existence of some mechanisms of fluid retention other than an infection of the bulla alone after operation. PMID- 8003873 TI - Anastomotic recurrence at hepaticojejunostomy in a long-term survivor of bile duct carcinoma: report of a case. AB - A rare case of autopsy-proven recurrence 10 years after a radical resection for lower bile duct carcinoma is herein reported. The subject is a 53-year-old man who underwent a curative resection of distal bile duct carcinoma with pancreatoduodenectomy in 1981. The lesion was a 1.0 x 1.5 x 1.0 cm well differentiated papillotubular adenocarcinoma invading the fibromuscular layer of the bile duct with a slight infiltration to the lymphatics but without any extension to the vessels, nerves, connective tissues, or nodes. The patient demonstrated a recurrence 10 years after the initial operation and died 4 months later. An autopsy revealed a 2.0 x 2.5 x 1.6 cm mass at the anastomotic site of hepaticojejunostomy without any distant metastases. Although a late anastomotic recurrence after more than 10 years is unique, this case highlights the difficulty of the operative eradication of bile duct carcinoma. As a result, all possible maneuvers either during or after operation to promote the prophylaxis of recurrence are warranted. PMID- 8003874 TI - The surgical technique of retroperitoneal lavage for the treatment of extended necrotizing pancreatitis. AB - For cases of extended necrotizing pancreatitis which involve the spread of infectious or hemorrhagic necrotic lesions to the retroperitoneal tissue, we recommend sequestrectomy and subsequent retroperitoneal lavage via the retroperitoneal access. For successful retroperitoneal lavage, as much liquefactive infectious necrotic tissue as possible should be removed from the retroperitoneal cavity during the operation. In addition, the necrotic cavity should be opened, adequately washed out, and catheters placed in the retroperitoneal cavity by retroperitoneal access. Although we have only applied this ideal technique in two patients so far, the details are presented herein. The significance of retroperitoneal lavage lies in the fact that it cleans the retroperitoneal foci of infection and necrosis, and that it eliminates the necrotic material, bacterial deposits, and biologically active substances produced after surgery. Ultimately, wound healing is markedly promoted, leading to improvement in the systemic condition. PMID- 8003876 TI - The status of regulation of assisted reproductive technology in the United States. PMID- 8003875 TI - Age limitation in human reproduction: is it justified? PMID- 8003877 TI - Review: microinjection of human sperm directly into human oocytes. PMID- 8003879 TI - Aneuploidy in spermatozoa using fluorescence in situ hybridization. PMID- 8003878 TI - Current progress in preimplantation genetic diagnosis. PMID- 8003880 TI - Embryonic platelet activating factor production in the rabbit increases during the preimplantation phase. AB - OBJECTIVE: This study measured platelet activating factor (PAF) production by rabbit embryos in vitro and ascertained if there is increased PAF production associated with advancing embryonic development. STUDY DESIGN: Two-cell rabbit embryos were recovered from superovulated New Zealand White does and cultured in vitro for 96 hr. Every 24 hr embryos were scored for developmental stage and PAF activity from the corresponding culture medium was measured by platelet aggregation and organic phosphate analyses. RESULTS: PAF was detected in culture medium at all stages from two cells to blastocysts and rose significantly (P < 0.001) at each 24-hr interval, reaching maximal levels at the expanded blastocyst stage. CONCLUSION: Maximal PAF production by expanded blastocysts may be an embryonic paracrine signal that facilitates implantation. PMID- 8003882 TI - In vivo survival of spermatozoa in the human fallopian tube for 25 days: a case report. PMID- 8003881 TI - Spectrophotometric analysis of human follicular fluid with regard to in vitro fertilization (IVF) parameters, follicular protein, and hormone content. AB - PURPOSE: Our purpose was to investigate possible relationships with spectrophotometric absorbance (458-nm region) and biochemical variables in follicular fluid (FF) as well as in vitro fertilization (IVF) outcome. METHODS: This study included 227 normal ovulatory women undergoing oocyte retrieval for IVF. Blood-uncontaminated fluid samples, identified by spectrophotometry, were investigated. Spectrophotometric absorbance of FF at 458 nm (n = 426), as well as hLH, FSH, PRL, hCG, testosterone, sialic acid, alpha 1-antitrypsin and plasminogen of selected fluids, was analyzed. RESULTS: Small-volume follicles (< or = 2 ml) were associated with higher absorbance profiles (P < 0.05), when compared to volumes greater than 2 ml. Our data suggest that the presence or absence of an oocyte, the potential of an oocyte to fertilize or cleave, failed to show any relationship with maximum FF absorbance at 458 nm. Maximum absorbances were significantly lower in FF from patients who subsequently became clinically pregnant (P = 0.039). No correlation between FF absorbances and biochemical parameters (P > 0.15) were established. CONCLUSIONS: Absorbance of clear FF at 458 nm should not be viewed as the single parameter to predict oocyte development in vitro. PMID- 8003883 TI - DiGeorge syndrome after in vitro fertilization. PMID- 8003884 TI - Spontaneous ovulation in functionally agonadal women prior to oocyte donation: incidence and remedies for avoiding cancellation. PMID- 8003885 TI - Association of higher pregnancy rates with low serum progesterone levels (by radioimmunoassay) at the time of human chorionic gonadotropin not corroborated when using a nonisotopic immunoassay. PMID- 8003887 TI - How could theory affect practice? PMID- 8003886 TI - Inadvertent exposure of early pregnancy to gonadotropin releasing hormone analogue. PMID- 8003888 TI - The NZNA code of ethics: does it help resolve ethical dilemmas in practice? PMID- 8003889 TI - New Zealand nursing. PMID- 8003891 TI - Financial recognition for a caring profession? PMID- 8003890 TI - Parents' recognition of illness in infants: a New Zealand pilot study of Baby Check. PMID- 8003892 TI - Are nurses out of touch? The healing art of massage in nursing curricula in New Zealand. PMID- 8003893 TI - Capturing a patient's readiness to learn. PMID- 8003895 TI - Picking up the pieces. PMID- 8003894 TI - The privileged place of nursing. PMID- 8003896 TI - A comparative analysis of transcultural nursing and cultural safety. PMID- 8003897 TI - [Crimean-Congo hemorrhagic fever in Senegal. Latest data on the ecology of the CCHF virus]. AB - The authors finalize the knowledge on the ecology of the CCHF virus in Senegal, West Africa. They specify two new major data for the understanding of the viral ecology in West Africa. The recognition of a bird species, common and widely distributed in Senegal (Tockus erythrorhynchus, Coraciiformes, Bucerotidae), that replicates the virus and infects the immature stages of its current parasite Hyalomma marginatum rufipes in more than 90% of the cases, explains why the minimum infection rate of the adults of this species of tick is always very high. The implication of Rhipicephalus evertsi evertsi in the viral ecology and/or a high efficiency of the transovarial transmission of the virus in Hy. m. rufipes would help to explain the maintenance of the endemy in the sahelian area. In the sahelian zone, Hy. marginatum rufipes must play the leading part, together with Rh. e. evertsi if vector, for the maintenance of the endemy. Hy. truncatum, the adults of which can readily bite man, ensures the vectorial transmission to him. In the sudanian zone, Amblyomma variegatum must play the same part as the Hyalomma and Rh. e. evertsi (if vector), and is surely the main vector to man, giving perhaps rise to less virulent strains (non hemorrhagic ones). PMID- 8003898 TI - [Resurgence of endemic yaws in Togo. Cause and eradication approach]. AB - In Togo, since 1940, yaws declared endemic has been controlled after the 1956 and 1961 eradication campaign. Nowadays, unfortunately, the mutilating treponematosis has reappeared in force. Hence, Togolese Health Officers are in search of ways and means to eradicate the disease so as to prevent handicaps for future generations. PMID- 8003899 TI - [Therapeutic approach in Mycobacterium ulcerans infections]. AB - In Cote d'Ivoire, 88 patients of a series of 124 cases with Buruli ulcer have been able to be treated and supervised. All of them have received local cares and various antibiotics, and 23 have been treated by islet skin graft. Among the numerous antibiotics used, only Streptomycin seems to be accompanied by an acceptable failure rate. The islet-graft presents the advantage of the technical simplicity, of the good tolerance face the infection and of a good successful rate, which permits to shorten the evolution of this disabling affection. It seems to be the best adapted procedure taking into account available medical means in most of tropical countries. PMID- 8003900 TI - [Importance of culture media choice in the isolation of Haemophilus ducreyi. Experience in Senegal]. AB - Genital ulcerations typify one of the major reasons clients seek STD consultation in developing countries. The usual etiologies are syphilis, chancroid and herpes. The ideal diagnostic approach is to undertake complete laboratory examination that are rarely possible in structure destitute of laboratory analysis possibilities which is the case for most of the STD transmission agents. Chancroid is caused by Haemophilus ducreyi, a short Gram negative bacteria. The bacteriological diagnosis is based on direct examination, isolation and identification of the bacteria. The nutritive exigence of the bacteria required 3 medium of isolation (PPLO base Pasteur), GC base (GIBCO) and Muller Hinton base (Becton & Dickinson, with "chocolate" agar) have been tested from the chancre samples of 108 male patients who had a median age of 31 years. Direct exams were positive in 66 cases (61%) and culture exams positive in 53 cases (49%). The Muller Hinton base with "chocolate" agar produced the best results and seems to be the medium of choice for isolated strains in Senegal. The culture mediums currently used in Europe are apparently inappropriate for the germ culture in Senegal. We have also observed that all the isolated strains were producers of beta-lactamase. Antibiotic treatment before the sample swab is taken seems to have an inhibiting effect on the culture. Direct examination with a sensibility of 94.3% and a specificity of 70.9% remains sufficient in routine presumptive diagnosis in endemic areas. PMID- 8003901 TI - [Leprosy in New Caledonia from 1983 to 1992. Histopathological and epidemiological data]. AB - New Caledonia is a South Pacific Island inhabited by more than 170,000 people: most of them are melanesians or europeans. Multidrug therapy for Hansen disease has been employed since 1983; so we made an epidemiologic and histopathologic study of the new cases diagnosed for 10 years, from 1983 to 1992. Local (clinical, histological, microbiological and immunological) means of diagnosis are described. In New Caledonia, the endemic level is lower than in the small neighbouring Pacific islands but there is still a native reservoir of Mycobacterium leprae with 40% multibacillary types. Nearly half of the new cases are less than 25 years old. They are often male melanesians. The diagnosis of indeterminate forms is debated when there is no acid-fast bacillus. Border-line forms are rare. Tuberculoid leprosy poses many differential diagnosis problems. Despite available multidrug therapy, one cannot yet consider that the incidence is decreasing significantly. PMID- 8003903 TI - [In vitro sensitivity of Vibrio cholerae serotype 0:139 to an intestinal antiseptic tiliquinol-tilbroquinol combination]. AB - O:139 is a new serotype of Vibrio cholerae that is not agglutinated by an O:1 antiserum but causes epidemics of cholera. Strains of O:139 serotype are resistant to O/129 compound and many antibiotics but are sensitive to tetracyclines and tiliquinol-tilbroquinol (Intetrix). The clinical management of the patients infected with serotype O:139 is identical to that of usual choleric patients. However, the immunological difference with O:1 serotype must lead to reconsider both the diagnosis and the vaccinating strategies of cholera. PMID- 8003902 TI - [Value of vibriocidal antibody research in endemic areas of Vibrio cholerae 0:1]. AB - We made vibriocidal antibody titration in the serum of some populations in Algeria and in Mali either during or between cholera epidemics. The seropositivity rate was 43.3% in healthy contacts in Alger in 1990 during an epidemic of cholera. For 12/16 healthy contacts examined two times in a 25-day interval, the seropositivity rate increased during the epidemic and the mean of antibody titres rose 8.88 folds. In Constantine, 53% of 195 blood donors had significant titres of vibriocidal antibodies in 1992, 6 years after an epidemic of cholera. The seropositivity rate in population seemed decreasing during this year. In Bamako, 46% of selected patients had significant vibriocidal antibody titres 8 years after the last epidemic of cholera in Mali. Seven of 10 children born after the epidemic had vibriocidal antibodies. These data confirm the persistence of vibriocidal antibodies in population during many years. The importance of the seropositivity rate in healthy contacts and in children born during a non epidemic period shows that asymptomatic infection is frequent and that Vibrio cholerae O:1 may be circulating in population between epidemics. As part of surveillance of cholera outbreaks in endemic areas, it might be of interest to study on a regular basis the vibriocidal antibody seropositivity rate in populations. PMID- 8003904 TI - [Tests for an early detection of pulmonary cryptococcosis by sputum culture]. AB - Cryptococcosis is a serious opportunistic infection occurring in acquired immunodeficiency syndrome (AIDS) patients. As the number of infected patients with the human immunodeficiency virus (HIV) in Central Africa and especially in Rwanda increases, the prevalence of cryptococcosis can also be expected to rise. An earlier diagnosis and treatment will improve the prognosis of cryptococcosis. As it is widely accepted that the lungs are the portal of entry for the yeast, 270 sputum samples coming from 230 patients attending the Centre Hospitalier de Kigali (CHK)--Rwanda for lung diseases, were investigated. Cr. neoformans var neoformans was cultured from 8 samples coming from 5 out of 230 patients. A retrospective review showed that 4 out of 5 patients were infected with HIV, a predisposing factor for cryptococcosis. PMID- 8003905 TI - [Invasions of Paederus sabaeus (Coleoptera Staphylinidae) in central Africa. 1. Entomological and epidemiological aspects]. AB - In May 1993, at the end of the rainy season, outbreaks of Paederus sabaeus (Coleoptera, Staphylinidae) were recorded in Brazzaville (Congo), Kinshasa (Zaire), Franceville and Libreville (Gabon) and even in Bangui (CAR) at the North of the equator. A short review of previous outbreaks in Africa and on vesicant substances is given by the authors. These beetles are attracted to neon lights and they rest on the walls or on the skin of the occupants. When the insects are crushed on the bare skin their haemolymph liberate pederine and related vesicant components which provocate dermatitis. The insects disappeared spontaneously after three to four weeks. PMID- 8003907 TI - [Decrease of natural immunity against Rift Valley fever in domestic ruminants of the Senegal River basin after the epizootic outbreak of 1987]. AB - A domestic ruminants serosurvey of Rift valley fever (RVF) neutralizing antibodies has been carried out during three years after the 1987 epidemic in the Senegal River Basin. Authors present results from the 1990 serosurvey that are matched with the preview surveys. Out of 1,225 ongulate tested, 17.2% had RVF virus antibodies. There is a global decrease in the herds immunity since the epizootic manifestation associated with the 1987 epidemic. Significant differences in seroprevalence are observed from the delta (28.5%) to the lower (17.9%) and middle valley (6.1%) of the Senegal river. Cattle are more likely to be with an higher seroprevalence than goat and sheep. PMID- 8003908 TI - [Tsetse and livestock in Central African Republic: retreat of Glossina morsitans submorsitans (Diptera, Glossinidae)]. AB - In the early 1960s, the most part of the Central African Republic was located inside the distribution area of Glossina morsitans submorsitans Newst. Since the last distribution studies of this tsetse in CAR (in 1963), the number of cattle has increased from 400,000 to approximately two millions, mainly of the Mbororo zebu breed. To set up the present distribution of G. m. submorsitans a study by trapping has been carried out in 27 livestock areas, regarding about 1,200 pastoralists' settlements. Furthermore, north-south transects have been made using both trapping (with bipyramidal traps laid every 2,000 meters) and net catching (within a car driving slowly). The result have shown the disappearance of G. m. submorsitans from the main livestock areas in the west (Bouar, Bozoum, Bocaranga, Batangafo, Bossangoa, Paoua), centre (Bossembele, Bouca, Dekoa) and east (Bambari, Grimari, Ippy). The southern border of the distribution area has been moved upwards to the north by up to 400 kilometres in the west of the country. This important retreat is discussed. It leads to a huge increase in the pastures available for the Mbororo pastoralists. Their access is still restricted in the centre-north and in the east by wild game reserves where G. m. submorsitans remains. PMID- 8003909 TI - [Evaluation of the immunological and entomological indices of yellow fever in the subprefecture of Tai, Ivory Coast]. AB - The authors report the results of a serological sample survey managed to evaluate the prevalence of yellow fever antibodies, connected with an entomological survey, in the area of Tai in Cote d'Ivoire. The refugee population has a high rate of non protected people, contrary to the Ivory population especially under 15 years old, because Cote d'Ivoire has included YF vaccine in his Expanded Programme on Immunization. A campaign of vaccination has been carried out. PMID- 8003906 TI - [Invasions of Paederus sabaeus (Coleoptera Staphylinidae) in central Africa. 2. Clinical and therapeutic aspects in Brazzaville]. AB - During the month of May 1993, at the end of the rainy season, an outbreak of dermatitis occurred in Brazzaville (Congo). It was caused by Paederus sabaeus, a Staphylinid beetle which invaded the town during three weeks. The patients recovered spontaneously or after topical application of creams. No eye affection was recorded. PMID- 8003910 TI - FDI policy statement on the human immunodeficiency virus (HIV), the acquired immune deficiency syndrome (AIDS), and dentistry. Revised August 1992. Federation Dentaire Internationale. PMID- 8003911 TI - The Koster health project. PMID- 8003913 TI - After 'The Killing Fields.' Dentistry in Cambodia. PMID- 8003912 TI - FDI Policy statement on fluorides and fluoridation for the prevention of dental caries. Federation Internationale Dentaire. PMID- 8003914 TI - Oral health needs of the elderly. PMID- 8003915 TI - Dental health and dental growth in the Bahamas. PMID- 8003916 TI - Oral health and oral health care of the elderly. PMID- 8003917 TI - An innovative method for isolation of the working field during bonding of multiple porcelain laminates. PMID- 8003918 TI - Source localization of brain electric field frequency bands during conscious, spontaneous, visual imagery and abstract thought. AB - This paper addresses the issue of mind-brain correspondence, using a novel way to reduce brain electric field data in the frequency domain to estimates of intracerebral model source locations, and applying this method to brain electric data collected during the 2-s epochs immediately before the randomly solicited reports of spontaneous, conscious, covert experiences from 12 normal volunteers. The mentation reports were classified into visual imagery and abstract thought. The mean locations of the EEG model sources associated with abstract thoughts were generally more anterior and deeper than those of visual imagery, particularly significant for the delta/theta band; the finding was common across subjects. Thus, different brain functional states involving different geometries of activated neural populations exist during conscious, spontaneous, task-free mentations of the visual imagery type and of the abstract thought type. PMID- 8003920 TI - Influence of reading habits on line bisection. AB - The effect of scanning direction on perception of space is studied with a visuo motor bisection task, among 120 normal dextrals with opposite reading habits (60 French subjects, 60 Israeli subjects). Bisection is found to depend upon subject's reading habits. Israeli bisected the line to the right of the objective centre, while French subjects placed their subjective middle to the left of the objective one. Results are discussed with respect to hemispheric activation theories, directional hypotheses and the neglect syndrome. PMID- 8003919 TI - The effects of inferior temporal and dorsolateral frontal lesions on serial-order behavior and visual imagery in monkeys. AB - Four monkeys were trained preoperatively on a serial-order task to respond to a set of five visual stimuli in a fixed sequence independent of their location. They were then given a test of visual imagery in which only two of the five stimuli appeared at a time, and the animals were required to respond to them in the order in which they appeared in the original sequence. The monkeys then received bilateral lesions of either inferior temporal cortex or dorsolateral frontal cortex. Dorsolateral frontal lesions had no effect on either serial-order behavior or visual imagery. In contrast, inferior temporal lesions severely impaired serial-order behavior. Once the serial-order task was relearned, however, the inferior temporal animals were completely normal on the test of visual imagery. PMID- 8003921 TI - Cognitive impairment following traumatic brain injury: the effect of pre- and post-injury administration of scopolamine and MK-801. AB - In order to examine the effectiveness of pre- and post-injury administration of muscarinic cholinergic and NMDA antagonists in reducing cognitive deficits following traumatic brain injury (TBI), rats were injected with either scopolamine (1 mg/kg) or MK-801 (0.3 mg/kg) 15 min prior to or 15 min after fluid percussion TBI. Cognitive performance was assessed with the Morris water maze procedure on days 11-15 after TBI or sham injury. When scopolamine and MK-801 were injected 15 min before injury, Morris water maze deficits were significantly reduced (P < 0.01 and P < 0.05, respectively). When scopolamine and MK-801 were injected 15 min after TBI, neither drug was effective in attenuating Morris water maze deficits. Consistent with other research, these results suggest that the cognitive deficits produced by TBI are the consequence of a brief period of excessive excitation of cholinergic and NMDA receptor systems. The results of this experiment also suggest that the temporal therapeutic window for the treatment of cognitive dysfunction with receptor antagonist intervention appears to be quite brief (< 15 min) in the rat. PMID- 8003922 TI - Anatomical substrates of auditory selective attention: behavioral and electrophysiological effects of posterior association cortex lesions. AB - Event-related brain potentials (ERPs) and reaction times (RTs) were recorded in an auditory selective attention task in control subjects and two groups of patients with lesions centered in (1) the temporal/parietal junction (T/P, n = 9); and (2) the inferior parietal lobe (IPL, n = 7). High pitched tones were presented to one ear and low pitched tones to the other in random sequences that included infrequent longer-duration tones and occasional novel sounds. Subjects attended to a specified ear and pressed a button to the longer-duration tones in that ear. IPL and T/P lesions slowed reaction times (RTs) and increased error rates, but improved one aspect of performance--patients showed less distraction than controls when targets followed novel sounds. T/P lesions reduced the amplitude of early sensory ERPs, initially over the damaged hemisphere (N1a, 70 110 ms) and then bilaterally (N1b, 110-130 ms, and N1c 130-160 ms). The reduction was accentuated for tones presented contralateral to the lesion, suggesting that N1 generators receive excitatory input primarily from the contralateral ear. IPL lesions reduced N1 amplitudes to both low frequency tones and novel sounds. Nd components associated with attentional selection were diminished over both hemispheres in the T/P group and over the lesioned hemisphere in the IPL group independent of ear of stimulation. Target and novel N2s tended to be diminished by IPL lesions but were unaffected by T/P lesions. The mismatch negativity was unaffected by either T/P or IPL lesions. The results support different roles of T/P and IPL cortex in auditory selective attention. PMID- 8003923 TI - The influence of long-term practice on mental rotation of 3-D objects. AB - We evaluated the influence of long-term practice on the performance of a mental rotation task in which subjects judged whether two 3-D objects presented in different orientations were identical. Stimuli and experimental conditions were analogous to those used by Shepard and Metzler. Sixteen subjects were selected, to test the influence of aptitude for mental imagery on this learning process. Subjects participated in 12 to 15 sessions over 6 weeks. Two catalogues of different stimuli were alternatively used during three (or six) consecutive sessions to determine the influence of complexity and familiarity of figures. For all subjects, the inverse of the velocity of mental rotation along the sessions was adequately fitted by a decreasing exponential curve. However, evidence for mental rotation did not disappear, even after 15 sessions. Asymptotic variations can be attributed to differences in stimuli as well as imaging skills of subjects. Our results lead to a new interpretation of the mental rotation process. PMID- 8003924 TI - Peripherally administered IL-1 alpha interferes with scopolamine-induced amnesia in mice. AB - We studied the effects of human recombinant interleukin-1 alpha on scopolamine induced amnesia for a passive avoidance response in the mouse. Post-training intraperitoneal administration of the cytokine (0.25 or 0.50 microgram/mouse) significantly reduced the amnesic effect of scopolamine (1.0 mg/kg i.p.). Our results indicate that peripheral interleukin-1 alpha can influence behavior and suggest the involvement of the cholinergic system in the neuromodulatory actions of this cytokine. PMID- 8003925 TI - The Online Journal of Knowledge Synthesis for Nursing. PMID- 8003926 TI - Venture into nursing cyberspace with the Virginia Henderson International Nursing Library. PMID- 8003927 TI - Making electronic resources work. PMID- 8003928 TI - Shared knowledge using collaborative tool. PMID- 8003930 TI - Research utilization: attitude and value. PMID- 8003929 TI - Now she belongs to the ages.... A pandimensional tribute to the extraordinary life of Martha E. Rogers. PMID- 8003931 TI - Jane Barnsteiner: pyramiding knowledge into practice. Interview by Julie Goldsmith. PMID- 8003932 TI - To advance the scientific base of nursing practice: the electronic library. PMID- 8003934 TI - Computer analysis of two-dimensional electrophoresis gels as a tool in cell biology: study of the protein expression of human keratinocytes from normal to tumor cells. AB - The usefulness of computer analysis of two-dimensional electrophoresis gels has been investigated on the example of human keratinocytes transformation. For this purpose, the protein expression of various keratinocytes strains from normal to tumor cells has been analysed by two-dimensional electrophoresis. The resulting gels have been submitted to computer analysis, including various data analysis techniques allowing to select spots on the gels or to classify the gels themselves. The latter techniques appeared very useful, since they demonstrated that the major transition in words of variation of the protein expression lies at the normal cell/transformed cell transition rather than at the transformed cell/tumorigenic cell transition. PMID- 8003933 TI - Comparison of three horizontal two-dimensional electrophoretic techniques to separate grass pollen allergens. AB - The identification and characterization of allergenic components are important for improving both diagnosis and therapy of allergy. We have studied grass pollen crude extract for better characterization of the allergen repertoire recognized by allergic patient IgE antibodies. Two-dimensional electrophoresis are the methods of choice to define physico-chemical characteristics of the allergens as they give isoelectric points and molecular mass of the analyzed samples. We compared the advantages and the drawbacks of three different ways to perform a two-dimensional electrophoresis. First, two gel media were compared to run native isoelectric focusing (IEF) with carrier ampholytes: agarose and acrylamide. With the introduction of immobilized pH gradient, highly resolutive and reproducible 2D electrophoresis could be obtained. This technique was also applied to separate the allergens of Dactylis glomerata pollen. PMID- 8003935 TI - 2D-page analysis: a practical guide to principle critical parameters. AB - Two-dimensional polyacrylamide gel electrophoresis (2D-PAGE) is a technique that is becoming more and more popular as the secrets of the critical parameters involved in its execution are being continually unravelled. The majority of these parameters are linked to the successful realization of the first dimension. Since the description of the original technique by O'Farrell in 1975, numerous studies have contributed to the improvement of the performance of 2D-PAGE. In this article, solutions to the problems most frequently encountered by 2D-PAGE users are given, such as cathodic drift, focusing at alkaline pH, the solubilization and the loading of the sample and different electrical parameters. PMID- 8003936 TI - Silver-staining of proteins in polyacrylamide gels: a general overview. AB - On the basis of the physico-chemical principles underlying silver-staining of proteins, which are recalled in this paper, several methods of silver-staining of proteins after SDS electrophoresis in polyacrylamide gels or isoelectric focusing were tested. The most valuable protocols are presented in this report, including standard methods for unsupported gels and new methods devised for thin (0.5 mm) supported gels for SDS electrophoresis or isoelectric focusing and for staining of small peptides. Generally speaking, the most rapid methods were found to be less sensitive and less reproducible than more time-consuming ones. Among the long methods, those using silver-diammine complex gave the most uniform sensitivity. They require however special home-made gels and cannot be applied to several electrophoretic systems (e.g. systems using tricine or bicine as the trailing ion, or isoelectric focusing in immobilized pH gradients). For these reasons, protocols based on silver nitrate are of a more general use and might be favored. Future trends for silver-staining will also be discussed. PMID- 8003937 TI - Image analysis of 2D gels: considerations and insights. AB - 2D gel experiments require computer based analysis when the number of gels exceed four and quantitative information is required. Computer based systems should first perform the required tasks and should do so with enough ease and logic that users in a biological laboratory can easily use it on an intermittent basis. Considerations for analysis systems including input device specifications needed, computer hardware configurations and software tools are discussed and compared to the application requirements. The components of this system are then examined as a whole to envision how the total solution should function optimally in an biological laboratory. PMID- 8003938 TI - Identification by 2D-page analysis of salt-stress induced proteins in radish (Raphanus sativus). AB - The response of Raphanus sativus to salinity has been investigated. Salt responsive proteins were detected by comparative 2D-PAGE analysis. Three polypeptides of 22, 28 and 28.5 kDa were isolated and subjected to microsequencing. The P22 possesses homology with members of the Kunitz family of trypsin inhibitor; the P28.5 is homologous to ascorbate peroxidase of several plant species while P28 did not exhibit significant homology with sequences archived in available databases. PMID- 8003939 TI - High resolution two-dimensional polyacrylamide gel electrophoresis using Immobilines. Application to the study of brain proteins. AB - Cytoplasmic soluble proteins of unknown origin but which could be associated with the development and maturation of the central nervous system are recognized by antibodies found in serum of patients with a paraneoplastic neurological syndrome. The associated antigens are of great interest in understanding these neurological pathologies. To study these antigens we describe and criticize a two dimensional polyacrylamide gel electrophoresis (2D-PAGE), using immobilized pH gradient (IPG) in first dimension. Proteins from brain complex mixtures were separated by this technique in order to identify and characterize (molecular weight, p-isoelectric point, sequencing) a protein of interest. Results prove the high reproducibility and the good resolution of the technique. Without applying enrichment method prior to 2D-PAGE, any proteins are not sequenceable after transblotting to PVDF (polyvinylidene difluoride) membrane and Coomassie blue staining. In these cases the meaning to reach the wanted aim, i.e. sequencing, was discussed. PMID- 8003940 TI - Analysis by two-dimensional gel electrophoresis of ram epididymal secreted proteins. AB - We used two-dimensional gel electrophoresis to analyse the 35S-labelled proteins secreted in vitro by the epithelium of the epididymis. Polypeptides with molecular weight ranging from 10 to > 200 kDa and isoelectric points from < 4 to 9 were observed. These compounds showed high degree of polymorphism. Some were secreted in distinct zones while others were present in the caput and the cauda epididymis. PMID- 8003941 TI - Possible biological functions for the expression of endogenous retroviral gene products in human placental tissues. AB - In human placental tissues the expression of the endogenous retroviral gene plays a particular role seeming responsible in the limitation of the diffusion of the exogenous retroviral particles. There is a peculiar significance of the role of proviral sequences, insertions and transcripts as well as of the hormones. Nevertheless the precise biological function remains at the greatest part ignored. PMID- 8003942 TI - The indirect participation of growth hormone in the thymocyte proliferation system. AB - The specific binding sites for growth hormone was recognized on both thymic lymphocytes (thymocytes) and thymus epithelial cells. The somatotropic action of GH is considered to be mediated mainly by insulin-like growth factor-1 (IGF-1) and partially by GH itself. In this study, effect of GH and IGF-1 on DNA synthetic activity of thymocytes was examined. By 48-hrs. culture with IGF-1 and 24-hrs. 3H-TdR pulse labeling, significant enhancement of DNA synthetic activity of thymocytes was detected, while the enhancement in the culture with GH was very weak. It is considered that IGF-1 acts on the cells in G0/G1 phase in cell cycle. The effect of IGF-1 on thymocyte proliferation was examined by using the thymocytes incubated 12 hrs. before IGF-1 stimulation and 3-hrs. 3H-TdR pulse labeling. The optimal condition to induce thymocyte proliferation was 15-hrs. culture with 380 ng/ml of IGF-1. Furthermore, 10 ng/ml or higher concentration of GH significantly increases IGF-1 release from TECs in confluent state. These results suggest that GH indirectly participates in thymus growth by increasing IGF-1 release from TECs, which enhances thymocyte proliferation. PMID- 8003943 TI - Specificity of rat liver plasma membrane serine/threonine protein kinases and phosphatases over endogenous proteins. AB - The specificity of rat liver plasma membrane protein kinases and phosphatases was examined over endogenous substrates, using specific effectors of these enzymes. cAMP-dependent protein kinase was shown to phosphorylate the 77, 60 and 51 kDa phosphoproteins and type II casein kinase, a specific 24 kDa one. On the contrary, types 1 and 2A protein phosphatases seemed to have a broad specificity in plasma membranes. An analysis of the phosphoprotein pattern based on the endogenous substrates of plasma membrane enzymes was deduced from these and other results from our laboratory. The specificity of some enzymes might arise from the anchorage in plasma membrane which might restrict their activity to their immediate environment. PMID- 8003944 TI - Age-related alterations of proteoglycan in mouse tracheal cartilage matrix: an electron histochemical analysis with the cationic dye of polyethyleneimine. AB - Age-related alterations of the proteoglycans (PGs) contents and size were observed in the tracheal cartilage matrix of ddY mice at various ages with the cationic dye of polyethyleneimine (PEI). In young animals (aged 1 day to 1 month after birth), the PGs content and size increased, resulting in the formation of the territorial matrix (TM) and the decrease of the space between the PEI aggregates and the collagen fibers. In 1 month old mice, the TM could be distinguished from the interterritorial matrix (ITM). In adult mice (from 2 to 6 months), the PGs content and size kept stable, but the rearrangement of the PGs and collagen fibers was observed. From 6 months of age on, the decrease of PGs content and size occurred mainly in the ITM. The developing stopping sign was recognized in 1 month and the senile sign from 6 months in the ddY mice as for the complete formation of the TM in 1 month and the decrease of the PGs content and size from 6 months. These results demonstrated the age-related alteration of PGs in the ultrastructural level first and could contribute to the aging study of the tracheal cartilage. PMID- 8003945 TI - Light and electron microscopic immunolocalization of L-asparaginase in the rat central nervous system. AB - The investigation on the localization of L-asparaginase, the enzyme involved in the synthesis of L-aspartic acid, has been carried out using the immunohistochemical method. Antibodies against this enzyme were obtained immunizing BALB/c mice with purified Escherichia coli L-asparaginase. Light microscopic observation revealed positive immunoreactivity in the great majority of neurons and glial cells, and electron microscopic analysis demonstrated immunological localization of the enzyme in the cytosol. The ubiquitous distribution of L-asparaginase suggests its involvement in many important functions of the central nervous system. PMID- 8003946 TI - Cathepsin L immunoreactivity in the hypothalamus of normal, streptozotocin diabetic and vasopressin-deficient Brattleboro rats. AB - The immunolocalization of cathepsin L in the hypothalamus of normal rats was compared with the distribution of the enzyme in streptozotocin-treated animals and in vasopressin-deficient rats (Brattleboro strain). In rats with a normal metabolic status the neurons of magnocellular nucl. supraopticus and paraventricularis stood out by intense immunostaining for cathepsin L. In rats suffering from an experimentally induced diabetes mellitus and in homozygous Brattleboro rats we observed a strong reduction in enzyme immunoreactivity in these nuclei. Since cathepsin L is capable of splitting certain hypothalamic neuropeptides that are changed in diabetic animals, a role of the enzyme in the metabolism of these peptides is imaginable. Decrease in immunoreactive cathepsin L in vasopressin-deficient rats points to a possible involvement of the enzyme in the control of fluid homeostasis. PMID- 8003947 TI - Rapid reduction of mRNA coding for 2'-5'-oligoadenylate synthetase in rat pheochromocytoma PC12 cells during apoptosis. AB - Apoptosis is a form of physiological cell death, characterized by DNA fragmentation, which often depends on RNA and protein synthesis. Because cellular RNA is also degraded during apoptosis we studied the role of the 2'-5' oligoadenylate (2-5A) synthetase in this process. The product of the synthetase, 2-5A, stimulates endoribonuclease-L-mediated controlled RNA degradation. Here we show that apoptosis is induced in rat phenochromocytoma PC12 cells by tributyltin (TBT) at low concentrations (1 nM); already 5-10 min. after addition of this compound DNA fragmentation resulting in a stepladder-like gel pattern was observed. The level of mRNA coding for 2-5A synthetase was determined using a cloned cDNA from rats. Sequence analyses of the rat 2-5A synthetase (M(r) 40 46,000) revealed high homology to other members of class I synthetase cloned from mouse and human. Applying the rat cDNA as a probe we found that parallel with degradation of DNA the level of mRNA coding for 2-5A synthetase decreased already 7.5 min. after induction of apoptosis by TBT the amount of 2-5A synthetase mRNA was reduced by 60%. This finding indicates that this enzyme is among those mRNAs which are degraded during apoptosis and it suggests that 2-5A synthetase, which is involved in the antiviral response of cells and most likely in the control of cell growth and differentiation, does not play an active role during this process. PMID- 8003948 TI - Demonstration of NADPH-diaphorase (NO-synthase) in the apocrine and eccrine skin glands of domesticated mammals. AB - The study demonstrates a strong enzyme histochemical and immunohistochemical reaction staining for NADPH-diaphorase/NO-synthase in the secretory cells of the apocrine glands in the hairy skin, and the eccrine glands in the foot pads of domesticated mammals. The results obtained are discussed in view of a regulatory action of the NO generated by these enzyme activities, implying a direct influence of NO on the contractile properties of glandular myoepithelial cells. In this way, a basic and simple mechanism to couple secretion production and secretion extrusion can be proposed. PMID- 8003950 TI - Enzymatic catalysis by lipase from Candida cylindracea: enantiomeric activity evaluation by 1H and 13C NMR. AB - Lipolytic enzymes represent an important class of biocatalysts and are widely used in the resolution of racemic mixtures. The activity of lipase from Candida cylindracea at different temperatures has been studied by NMR determination of the enantiomeric excess in the enantioselective hydrolysis of 2-arylpropionic acid esters of pharmacological interest. At a purpose, a system based on Europium (III) chiral shift reagent has been settled and utilized. PMID- 8003949 TI - Age related effects of lectins on GAG metabolism in cultured embryonic fibroblasts. AB - Lectins (WGA, SBA or PNA) were administered to 7 and 14 days chick embryo fibroblasts to evaluate their ability to influence GAG cellular and extracellular accumulation. HA and sulphated GAG were differently affected by lectins. WGA addition to culture medium enhanced HA and sulphated GAG in the two examined compartments. SBA and PNA increased sulphated GAG only in the cellular pool with a consequent reduction of secreted GAG. As far as HA is concerned, SBA and PNA promoted its accumulation in the extracellular compartment. NH4Cl administration indicated a decline of GAG degradation in the course of development in presence of lectins. Generally the effect of lectins was greater in the youngest stage: showing that lectins were able to bind 7 and 14 days-old fibroblasts differently. PMID- 8003951 TI - The proopiomelanocortin (POMC) gene expression of AtT20 mouse pituitary cells is dependent on cell culture conditions. AB - We have compared the properties of AtT20 cells cultivated in a Dulbecco's modified Eagles medium containing 10% fetal calf serum (FCS) and of AtT20 cells adapted to a chemically better defined medium with transferrin, albumin, insulin, sodium selenit and 0.2% FCS. Our interest was focused on the hypothalamo pituitary-adrenal axis (HPA) involved adrenocorticotropic hormone (ACTH) and the potent opioid peptide beta-endorphin (beta-END). There were no differences in basal secretion of ACTH and beta-END by cells cultivated in medium containing 10% or 0.2% serum, respectively. In combination to the decreased proliferation activity of AtT20 cells, grown in the serum-reduced medium we found a strongly enhanced ACTH secretion activity stimulated by the corticotropin releasing hormone (CRH) in contrast to normally cultivated AtT20 cells (10% serum). In addition, the proopiomelanocortin (POMC) gene expression was significantly down regulated in serum-reduced medium and was normalized again after further cultivation in a 10% serum containing medium. This leads to the conclusion that under standard conditions (10% serum) the gene transcription is increased by hitherto uncharacterized modulators present in the serum. The unexpected unchanged amounts of ACTH and beta-End could be the result of increased protein convertases activities. These enzymes are responsible for the POMC precursor processing into beta-End and ACTH. PMID- 8003952 TI - Murine prosaposin: expression in the reproductive system of a gene implicated in human genetic disease. PMID- 8003953 TI - "Frozen" dynamic dimer model for transmembrane signaling in bacterial chemotaxis receptors. AB - The crystal structures of the ligand binding domain of a bacterial aspartate receptor suggest a simple mechanism for transmembrane signaling by the dimer of the receptor. On ligand binding, one domain rotates with respect to the other, and this rotational motion is proposed to be transmitted through the membrane to the cytoplasmic domains of the receptor. PMID- 8003954 TI - Crystal structure of cholera toxin B-pentamer bound to receptor GM1 pentasaccharide. AB - Cholera toxin (CT) is an AB5 hexameric protein responsible for the symptoms produced by Vibrio cholerae infection. In the first step of cell intoxication, the B-pentamer of the toxin binds specifically to the branched pentasaccharide moiety of ganglioside GM1 on the surface of target human intestinal epithelial cells. We present here the crystal structure of the cholera toxin B-pentamer complexed with the GM1 pentasaccharide. Each receptor binding site on the toxin is found to lie primarily within a single B-subunit, with a single solvent mediated hydrogen bond from residue Gly 33 of an adjacent subunit. The large majority of interactions between the receptor and the toxin involve the 2 terminal sugars of GM1, galactose and sialic acid, with a smaller contribution from the N-acetyl galactosamine residue. The binding of GM1 to cholera toxin thus resembles a 2-fingered grip: the Gal(beta 1-3)GalNAc moiety representing the "forefinger" and the sialic acid representing the "thumb." The residues forming the binding site are conserved between cholera toxin and the homologous heat labile enterotoxin from Escherichia coli, with the sole exception of His 13. Some reported differences in the binding affinity of the 2 toxins for gangliosides other than GM1 may be rationalized by sequence differences at this residue. The CTB5:GM1 pentasaccharide complex described here provides a detailed view of a protein:ganglioside specific binding interaction, and as such is of interest not only for understanding cholera pathogenesis and for the design of drugs and development of vaccines but also for modeling other protein:ganglioside interactions such as those involved in GM1-mediated signal transduction. PMID- 8003956 TI - Structure and dynamics of the active site gorge of acetylcholinesterase: synergistic use of molecular dynamics simulation and X-ray crystallography. AB - The active site of acetylcholinesterase (AChE) from Torpedo californica is located 20 A from the enzyme surface at the bottom of a narrow gorge. To understand the role of this gorge in the function of AChE, we have studied simulations of its molecular dynamics. When simulations were conducted with pure water filling the gorge, residues in the vicinity of the active site deviated quickly and markedly from the crystal structure. Further study of the original crystallographic data suggests that a bis-quaternary decamethonium (DECA) ion, acquired during enzyme purification, residues in the gorge. There is additional electron density within the gorge that may represent small bound cations. When DECA and 2 cations are placed within the gorge, the simulation and the crystal structure are dramatically reconciled. The small cations, more so than DECA, appear to stabilize part of the gorge wall through electrostatic interactions. This part of the gorge wall is relatively thin and may regulate substrate, product, and water movement through the active site. PMID- 8003955 TI - cAMP-dependent protein kinase: crystallographic insights into substrate recognition and phosphotransfer. AB - The crystal structure of ternary and binary substrate complexes of the catalytic subunit of cAMP-dependent protein kinase has been refined at 2.2 and 2.25 A resolution, respectively. The ternary complex contains ADP and a 20-residue substrate peptide, whereas the binary complex contains the phosphorylated substrate peptide. These 2 structures were refined to crystallographic R-factors of 17.5 and 18.1%, respectively. In the ternary complex, the hydroxyl oxygen OG of the serine at the P-site is 2.7 A from the OD1 atom of Asp 166. This is the first crystallographic evidence showing the direct interaction of this invariant carboxylate with a peptide substrate, and supports the predicted role of Asp 166 as a catalytic base and as an agent to position the serine -OH for nucleophilic attack. A comparison of the substrate and inhibitor ternary complexes places the hydroxyl oxygen of the serine 2.7 A from the gamma-phosphate of ATP and supports a direct in-line mechanism for phosphotransfer. In the binary complex, the phosphate on the Ser interacts directly with the epsilon N of Lys 168, another conserved residue. In the ternary complex containing ATP and the inhibitor peptide, Lys 168 interacts electrostatically with the gamma-phosphate of ATP (Zheng J, Knighton DR, Ten Eyck LF, Karlsson R, Xuong NH, Taylor SS, Sowadski JM, 1993, Biochemistry 32:2154-2161). Thus, Lys 168 remains closely associated with the phosphate in both complexes. A comparison of this binary complex structure with the recently solved structure of the ternary complex containing ATP and inhibitor peptide also reveals that the phosphate atom traverses a distance of about 1.5 A following nucleophilic attack by serine and transfer to the peptide. No major conformational changes of active site residues are seen when the substrate and product complexes are compared, although the binary complex with the phosphopeptide reveals localized changes in conformation in the region corresponding to the glycine-rich loop. The high B-factors for this loop support the conclusion that this structural motif is a highly mobile segment of the protein. PMID- 8003957 TI - Sculpting proteins interactively: continual energy minimization embedded in a graphical modeling system. AB - We describe a new paradigm for modeling proteins in interactive computer graphics systems--continual maintenance of a physically valid representation, combined with direct user control and visualization. This is achieved by a fast algorithm for energy minimization, capable of real-time performance on all atoms of a small protein, plus graphically specified user tugs. The modeling system, called Sculpt, rigidly constrains bond lengths, bond angles, and planar groups (similar to existing interactive modeling programs), while it applies elastic restraints to minimize the potential energy due to torsions, hydrogen bonds, and van der Waals and electrostatic interactions (similar to existing batch minimization programs), and user-specified springs. The graphical interface can show bad and/or favorable contacts, and individual energy terms can be turned on or off to determine their effects and interactions. Sculpt finds a local minimum of the total energy that satisfies all the constraints using an augmented Lagrange multiplier method; calculation time increases only linearly with the number of atoms because the matrix of constraint gradients is sparse and banded. On a 100 MHz MIPS R4000 processor (Silicon Graphics Indigo), Sculpt achieves 11 updates per second on a 20-residue fragment and 2 updates per second on an 80-residue protein, using all atoms except non-H-bonding hydrogens, and without electrostatic interactions. Applications of Sculpt are described: to reverse the direction of bundle packing in a designed 4-helix bundle protein, to fold up a 2 stranded beta-ribbon into an approximate beta-barrel, and to design the sequence and conformation of a 30-residue peptide that mimics one partner of a protein subunit interaction. Computer models that are both interactive and physically realistic (within the limitations of a given force field) have 2 significant advantages: (1) they make feasible the modeling of very large changes (such as needed for de novo design), and (2) they help the user understand how different energy terms interact to stabilize a given conformation. The Sculpt paradigm combines many of the best features of interactive graphical modeling, energy minimization, and actual physical models, and we propose it as an especially productive way to use current and future increases in computer speed. PMID- 8003958 TI - Do salt bridges stabilize proteins? A continuum electrostatic analysis. AB - The electrostatic contribution to the free energy of folding was calculated for 21 salt bridges in 9 protein X-ray crystal structures using a continuum electrostatic approach with the DELPHI computer-program package. The majority (17) were found to be electrostatically destabilizing; the average free energy change, which is analogous to mutation of salt bridging side chains to hydrophobic isosteres, was calculated to be 3.5 kcal/mol. This is fundamentally different from stability measurements using pKa shifts, which effectively measure the strength of a salt bridge relative to 1 or more charged hydrogen bonds. The calculated effect was due to a large, unfavorable desolvation contribution that was not fully compensated by favorable interactions within the salt bridge and between salt-bridge partners and other polar and charged groups in the folded protein. Some of the salt bridges were studied in further detail to determine the effect of the choice of values for atomic radii, internal protein dielectric constant, and ionic strength used in the calculations. Increased ionic strength resulted in little or no change in calculated stability for 3 of 4 salt bridges over a range of 0.1-0.9 M. The results suggest that mutation of salt bridges, particularly those that are buried, to "hydrophobic bridges" (that pack at least as well as wild type) can result in proteins with increased stability. Due to the large penalty for burying uncompensated ionizable groups, salt bridges could help to limit the number of low free energy conformations of a molecule or complex and thus play a role in determining specificity (i.e., the uniqueness of a protein fold or protein-ligand binding geometry). PMID- 8003959 TI - Role of the Cys 2-Cys 10 disulfide bond for the structure, stability, and folding kinetics of ribonuclease T1. AB - The Cys 2-Cys 10 disulfide bond in ribonuclease T1 was broken by substituting Cys 2 and Cys 10 by Ser and Asn, respectively, as present in ribonuclease F1. This C2S/C10N variant resembles the wild-type protein in structure and in catalytic activity. Minor structural changes were observed by 2-dimensional NMR in the local environment of the substituted amino acids only. The thermodynamic stability of ribonuclease T1 is strongly reduced by breaking the Cys 2-Cys 10 bond, and the free energy of denaturation is decreased by about 10 kJ/mol. The folding mechanism is not affected, and the trans to cis isomerizations of Pro 39 and Pro 55 are still the rate-limiting steps of the folding process. The differences in the time courses of unfolding and refolding are correlated with the decrease in stability: the folding kinetics of the wild-type protein and the C2S/C10N variant become indistinguishable when they are compared under conditions of identical stability. Apparently, the Cys 2-Cys 10 disulfide bond is important for the stability but not for the folding mechanism of ribonuclease T1. The breaking of this bond has the same effect on stability and folding kinetics as adding 1 M guanidinium chloride to the wild-type protein. PMID- 8003961 TI - Interaction of semisynthetic variants of RNase A with ribonuclease inhibitor. AB - Derivatives of ribonuclease A (RNase A) with modifications in positions 1 and/or 7 were prepared by subtilisin-catalyzed semisynthesis starting from synthetic RNase 1-20 peptides and S-protein (RNase 21-124). The lysyl residue at position 1 was replaced by alanine, whereas Lys-7 was replaced by cysteine that was specifically modified prior to semisynthesis. The enzymes obtained were characterized by protein chemical methods and were active toward uridylyl-3',5' adenosine and yeast RNA. When Lys-7 was replaced by S-methyl-cysteine or S carboxamido-contrast, the catalytic properties were only slightly altered. The dissociation constant for the RNase A-RI complex increased from 74 fM (RNase A) to 4.5 pM (Lys-1, Cys-7-methyl RNase), corresponding to a decrease in binding energy of 10 kJ mol-1. Modifications that introduced a positive charge in position 7 (S-aminoethyl- or S-ethylpyridyl-cysteine) led to much smaller losses. The replacement of Lys-1 resulted in a 4-kJ mol-1 loss in binding energy. S protein bound to RI with Ki = 63.4 pM, 800-fold weaker than RNase A. This corresponded to a 16-kJ mol-1 difference in binding energy. The results show that the N-terminal portion of RNase A contributes significantly to binding of ribonuclease inhibitor and that ionic interactions of Lys-7 and to a smaller extent of Lys-1 provide most of the binding energy. PMID- 8003960 TI - Cysteine scanning mutagenesis of the N-terminal 32 amino acid residues in the lactose permease of Escherichia coli. AB - Using a functional lactose permease mutant devoid of Cys residues (C-less permease), each amino acid residue in the hydrophilic N-terminus and the first putative transmembrane helix was systematically replaced with Cys (from Tyr-2 to Trp-33). Twenty-three of 32 mutants exhibit high lactose accumulation (70-100% or more of C-less), and an additional 8 mutants accumulate to lower but highly significant levels. Surprisingly, Cys replacement for Gly-24 or Tyr-26 yields fully active permease molecules, and permease with Cys in place of Pro-28 also exhibits significant transport activity, although previous mutagenesis studies on these residues suggested that they may be required for lactose transport. As expected, Cys replacement for Pro-31 completely inactivates, in agreement with previous findings indicating that "helix-breaking" propensity at this position is necessary for full activity (Consler TG, Tsolas O, Kaback HR, 1991, Biochemistry 30:1291-1297). Twenty-nine mutants are present in the membrane in amounts comparable to C-less permease, whereas membrane levels of mutants Tyr-3-->Cys and Phe-12-->Cys are slightly reduced, as judged by immunological techniques. Dramatically, mutant Phe-9-->Cys is hardly detectable when expressed from the lac promoter/operator at a relatively low rate, but is present in the membrane in a stable form when expressed at a high rate from the T7 promoter. Finally, studies with N-ethylmalemide show that 6 Cys-replacement mutants that cluster at the C terminal end of putative helix I are inactivated significantly.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8003962 TI - Real-time DNA binding measurements of the ETS1 recombinant oncoproteins reveal significant kinetic differences between the p42 and p51 isoforms. AB - The sequence-specific DNA binding of recombinant p42 and p51 ETS1 oncoprotein was examined quantitatively to determine whether the loss of the Exon VII phosphorylation domain in p42 ETS1 or the phosphorylation of expressed Exon VII in p51 ETS1 had an effect on DNA binding activity. The kinetics of sequence specific DNA binding was measured using real-time changes in surface plasmon resonance with BIAcore (registered trademark, Pharmacia Biosensor) technology. The real-time binding of p42 and p51 ETS1 displayed significant differences in kinetic behavior. p51 ETS1 is characterized by a fast initial binding and conversion to a stable complex, whereas p42 ETS1 exhibits a slow initial binding and conversion to a stable complex. All of the p51 ETS1 DNA binding states are characterized by rapid turnover, whereas the p42 ETS1 DNA binding states are 4-20 times more stable. A model describing these kinetic steps is presented. Stoichiometric titrations of either p42 or p51 ETS1 with specific oligonucleotides show 1:1 complex formation. The DNA sequence specificity of the p42 and p51 ETS1 as determined by mutational analysis was similar. The in vitro phosphorylation of p51 ETS1 by CAM kinase II obliterates its binding to specific DNA, suggesting that the regulation of p51 ETS1 sequence-specific DNA binding occurs through phosphorylation by a calcium-dependent second messenger. The p42 ETS1 lacks this regulatory domain (Exon VII), and binding to its specific DNA sequence is not sensitive to calcium signaling. PMID- 8003963 TI - The native state of apomyoglobin described by proton NMR spectroscopy: interaction with the paramagnetic probe HyTEMPO and the fluorescent dye ANS. AB - Proton NMR experiments were carried out on apomyoglobin from sperm whale and horse skeletal muscle. Two small molecules, the paramagnetic relaxation agent 4 hydroxy-2,2,6,6-tetramethylpiperidinyl-1-oxy (HyTEMPO) and the fluorescent dye 8 anilino-1-naphthalenesulfonic acid (ANS), were used to alter and simplify the spectrum. Both were shown to bind in the heme pocket by docking onto the hydrophobic residues lining the distal side. Only 1 extensive region of the apoprotein structure, composed of hydrophobic residues, is not affected by HyTEMPO. It includes the 2 tryptophans (located in the A helix), other nonpolar residues of the A helix and side chains from the E, G, and GH helices. The spectral perturbations induced by ANS allowed assignment of the distal histidine (His-64) in horse apomyoglobin. This residue was previously reported to titrate with a pKa below 5 and tentatively labeled as His-82 on the basis of this value (Cocco MJ, Kao YH, Phillips AT, Lecomte JTJ, 1992, Biochemistry 31:6481-6491). The packing of the side chains and the low pKa of His-64 reinforce the idea that the distal side of the binding site is folded in a manner closely related to that in the holoprotein. ANS was found to sharpen the protein signals and the improvement of the spectral resolution facilitated the assignment of backbone amide resonances. Secondary structure, as manifested in characteristic inter amide proton NOEs, was detected in the A, B, C, E, G, and H helices. The combined information on the hydrophobic cores and the secondary structure composes an improved representation of the native state of apomyoglobin. PMID- 8003964 TI - Enzyme IIBcellobiose of the phosphoenol-pyruvate-dependent phosphotransferase system of Escherichia coli: backbone assignment and secondary structure determined by three-dimensional NMR spectroscopy. AB - The assignment of backbone resonances and the secondary structure determination of the Cys 10 Ser mutant of enzyme IIBcellobiose of the Escherichia coli cellobiose-specific phosphoenol-pyruvate-dependent phosphotransferase system are presented. The backbone resonances were assigned using 4 triple resonance experiments, the HNCA and HN(CO)CA experiments, correlating backbone 1H, 15N, and 13C alpha resonances, and the HN(CA)CO and HNCO experiments, correlating backbone 1H,15N and 13CO resonances. Heteronuclear 1H-NOE 1H-15N single quantum coherence (15N-NOESY-HSQC) spectroscopy and heteronuclear 1H total correlation 1H-15N single quantum coherence (15N-TOCSY-HSQC) spectroscopy were used to resolve ambiguities arising from overlapping 13C alpha and 13CO frequencies and to check the assignments from the triple resonance experiments. This procedure, together with a 3-dimensional 1H alpha-13C alpha-13CO experiment (COCAH), yielded the assignment for all observed backbone resonances. The secondary structure was determined using information both from the deviation of observed 1H alpha and 13C alpha chemical shifts from their random coil values and 1H-NOE information from the 15N-NOESY-HSQC. These data show that enzyme IIBcellobiose consists of a 4 stranded parallel beta-sheet and 5 alpha-helices. In the wild-type enzyme IIBcellobiose, the catalytic residue appears to be located at the end of a beta strand. PMID- 8003965 TI - An 1H NMR determination of the three-dimensional structures of mirror-image forms of a Leu-5 variant of the trypsin inhibitor from Ecballium elaterium (EETI-II). AB - The 3-dimensional structures of mirror-image forms of a Leu-5 variant of the trypsin inhibitor Ecballium elaterium (EETI-II) have been determined by 1H NMR spectroscopy and simulated annealing calculations incorporating NOE-derived distance constraints. Spectra were assigned using 2-dimensional NMR methods at 400 MHz, and internuclear distances were determined from NOESY experiments. Three bond spin-spin couplings between C alpha H and amide protons, amide exchange rates, and the temperature dependence of amide chemical shifts were also measured. The structure consists largely of loops and turns, with a short region of beta-sheet. The Leu-5 substitution produces a substantial reduction in affinity for trypsin relative to native EETI-II, which contains an Ile at this position. The global structure of the Leu-5 analogue studied here is similar to that reported for native EETI-II (Heitz A, Chiche L, Le-Nguyen D, Castro B, 1989, Biochemistry 28:2392-2398) and to X-ray and NMR structures of the related proteinase inhibitor CMTI-I (Bode W et al., 1989, FEBS Lett 242:285-292; Holak TA et al., 1989a, J Mol Biol 210:649-654; Holak TA, Gondol D, Otlewski J, Wilusz T, 1989b, J Mol Biol 210:635-648; Holak TA, Habazettl J, Oschkinat H, Otlewski J, 1991, J Am Chem Soc 113:3196-3198). The region near the scissile bond is the most disordered part of the structure, based on geometric superimposition of 40 calculated structures. This disorder most likely reflects additional motion being present in this region relative to the rest of the protein. This motional disorder is increased in the Leu-5 analogue relative to the native form and may be responsible for its reduced trypsin binding. A second form of the protein synthesized with all (D) amino acids was also studied by NMR and found to have a spectrum identical with that of the (L) form. This is consistent with the (D) form being a mirror image of the (L) form and not distinguishable by NMR in an achiral solvent (i.e., H2O). The (D) form has no activity against trypsin, as would be expected for a mirror-image form. PMID- 8003966 TI - The 2.6-A refined structure of the Escherichia coli recombinant Saccharomyces cerevisiae flavocytochrome b2-sulfite complex. AB - Flavocytochrome b2 from Saccharomyces cerevisiae catalyzes the oxidation of L lactate to pyruvate and the electron transfer to cytochrome c in the mitochondrial intermembrane space. It is a homotetramer with a molecular weight of 4 x 58 kDa, each monomer of which is composed of 2 distinct domains, the one carrying FMN and the other, a "b5-like" heme. The native structure has been described at a resolution of 2.4 A (Xia ZX, Mathews FS, 1990, J Mol Biol 212:837 863). The heme domains protrude from the central body of the tetramer consisting of the 4 FMN binding domains. Because only 2 heme domains are visible in the electron density map, the other 2 are probably disordered. We crystallized the Escherichia coli recombinant flavocytochrome b2 from S. cerevisiae inhibited by sulfite. Although the crystals were obtained under very different conditions from those of the pyruvate-containing native enzyme, they were found to be isostructural (P 3(2) 2 1, a = b = 164.5 A, c = 114.0 A). The 2.6-A X-ray structure was extensively refined with X-PLOR (R = 17.3%), which made it possible to describe in detail the recombinant flavocytochrome b2 molecular structure. There exist few differences between the native and recombinant structures, in line with the fact that they show similar kinetic behavior, and they further confirm the intrinsic mobility of the heme domain (Labeyrie F, Beloil JC, Thomas MA, 1988, Biochim Biophys Acta 953:134-141). This structure will be used as a starting model in the structural resolution of flavocytochrome b2 point mutants. PMID- 8003967 TI - Characterization of a truncated form of arrestin isolated from bovine rod outer segments. AB - The inactivation of photolyzed rhodopsin requires phosphorylation of the receptor and binding of a 48-kDa regulatory protein, arrestin. By binding to phosphorylated photolyzed rhodopsin, arrestin inhibits G protein (Gt) activation and blocks premature dephosphorylation, thereby preventing the reentry of photolyzed rhodopsin into the phototransduction pathway. In this study, we isolated a 44-kDa form of arrestin, called p44, from fresh bovine rod outer segments and characterized its structure and function. A partial primary structure of p44 was established by a combination of mass spectrometry and automated Edman degradation of proteolytic peptides. The amino acid sequence was found to be identical with arrestin, except that the C-terminal 35 residues (positions 370-404) are replaced by a single alanine. p44 appeared to be generated by alternative mRNA splicing, because intron 15 interrupts within the nucleotide codon for 369Ser in the arrestin gene. Functionally, p44 binds avidly to photolyzed or phosphorylated and photolyzed rhodopsin. As a consequence of its relatively high affinity for bleached rhodopsin, p44 blocks Gt activation. The binding characteristics of p44 set it apart from tryptic forms of arrestin (truncated at the N- and C-termini), which require phosphorylation of rhodopsin for tight binding. We propose that p44 is a novel splice variant of arrestin that could be involved in the regulation of Gt activation. PMID- 8003969 TI - Rational design of a three-heptad coiled-coil protein and comparison by molecular dynamics simulation with the GCN4 coiled coil: presence of interior three-center hydrogen bonds. AB - alpha-Helical coiled coils have a 7-residue repeating pattern (abcdefg) where a and d are usually hydrophobic. We have designed a 2-stranded 44-residue coiled coil protein (P44) consisting of 2 22-residue alpha-helices linked by 2 terminal disulfide groups to test whether the disulfide bridges could stabilize a 3-heptad coiled coil. P44 should be stabilized by intrahelical hydrogen bonds, interhelical disulfide and salt bridges, and interior hydrophobic interactions. A computer model of P44 was built and its stability was studied by molecular dynamics simulation with explicit water. This doubly crosslinked 3-heptad coiled coil did not unfold during a 300-ps simulation with explicit water. This doubly crosslinked 3-heptad coiled coil did not unfold during a 300-ps simulation. But reduced P44 with 4 thiol groups did unfold. For comparison, the 62-residue crystal structure of the 4-heptad coiled coil of transcription activator GCN4 did not unfold during a 300-ps simulation. Thus P44 may be a stable folded protein in aqueous solution. These simulations revealed the presence of 2 local hydrogen bond networks involving intra-helical 3-center hydrogen bonds in the hydrophobic interior of the coiled coils of GCN4 and P44. The NH hydrogen at d makes a 3 center hydrogen bond whose major component is to the i - 4 C = O oxygen at g and minor component is to the solvent-inaccessible i - 3 C = O oxygen at a. Likewise, the NH hydrogen at g makes a 3-center hydrogen bond with the i - 4 C = O oxygen at c and the buried i - 3 C = O oxygen at d. PMID- 8003970 TI - Conserved sequence pattern in a wide variety of phosphoesterases. AB - A unique sequence pattern, designated the GD/GNH signature, was shown to be conserved in a wide variety of phosphoesterases. The enzymes containing this signature cleave phosphoester bonds in such different substrates as (1) phosphoserine and phosphothreonine in polypeptides; (2) bis(5'-nucleosidyl) tetraphosphates; (3) nucleoside 5' phosphates; (4) 2',3'-cyclic nucleotide phosphates; (5) polynucleotides; (6) 2'-5' phosphodiesters in RNA (intron) lariats; (7) sphingomyelin; and (7) various phosphomonoesters. Two conserved acidic amino acid residues and a conserved histidine residue may be directly involved in phosphoester bond cleavage. PMID- 8003968 TI - Sequence relationships between integral inner membrane proteins of binding protein-dependent transport systems: evolution by recurrent gene duplications. AB - Periplasmic binding protein-dependent transport systems are composed of a periplasmic substrate-binding protein, a set of 2 (sometimes 1) very hydrophobic integral membrane proteins, and 1 (sometimes 2) hydrophilic peripheral membrane protein that binds and hydrolyzes ATP. These systems are members of the superfamily of ABC transporters. We performed a molecular phylogenetic analysis of the sequences of 70 hydrophobic membrane proteins of these transport systems in order to investigate their evolutionary history. Proteins were grouped into 8 clusters. Within each cluster, protein sequences displayed significant similarities, suggesting that they derive from a common ancestor. Most clusters contained proteins from systems transporting analogous substrates such as monosaccharides, oligopeptides, or hydrophobic amino acids, but this was not a general rule. Proteins from diverse bacteria are found within each cluster, suggesting that the ancestors of current clusters were present before the divergence of bacterial groups. The phylogenetic trees computed for hydrophobic membrane proteins of these permeases are similar to those described for the periplasmic substrate-binding proteins. This result suggests that the genetic regions encoding binding protein-dependent permeases evolved as whole units. Based on the results of the classification of the proteins and on the reconstructed phylogenetic trees, we propose an evolutionary scheme for periplasmic permeases. According to this model, it is probable that these transport systems derive from an ancestral system having only 1 hydrophobic membrane protein.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8003971 TI - Acid sphingomyelinase possesses a domain homologous to its activator proteins: saposins B and D. AB - An N-terminal region of the acid sphingomyelinase sequence (residues 89-165) is shown to be homologous to saposin-type sequences. By analogy with the known functions of saposins, this sphingomyelinase saposin-type domain may possess lipid-binding and/or sphingomyelinase-activator properties. This finding may prove to be important in the understanding of Niemann-Pick disease, which results from sphingomyelinase deficiency. PMID- 8003972 TI - A structural role for arginine in proteins: multiple hydrogen bonds to backbone carbonyl oxygens. AB - We propose that arginine side chains often play a previously unappreciated general structural role in the maintenance of tertiary structure in proteins, wherein the positively charged guanidinium group forms multiple hydrogen bonds to backbone carbonyl oxygens. Using as a criterion for a "structural" arginine one that forms 4 or more hydrogen bonds to 3 or more backbone carbonyl oxygens, we have used molecular graphics to locate arginines of interest in 4 proteins: Arg 180 in Thermus thermophilus manganese superoxide dismutase, Arg 254 in human carbonic anhydrase II, Arg 31 in Streptomyces rubiginosus xylose isomerase, and Arg 313 in Rhodospirillum rubrum ribulose-1,5-bisphosphate carboxylase/oxygenase. Arg 180 helps to mold the active site channel of superoxide dismutase, whereas in each of the other enzymes the structural arginine is buried in the "mantle" (i.e., inside, but near the surface) of the protein interior well removed from the active site, where it makes 5 hydrogen bonds to 4 backbone carbonyl oxygens. Using a more relaxed criterion of 3 or more hydrogen bonds to 2 or more backbone carbonyl oxygens, arginines that play a potentially important structural role were found in yeast enolase, Bacillus stearothermophilus glyceraldehyde-3 phosphate dehydrogenase, bacteriophage T4 and human lysozymes, Enteromorpha prolifera plastocyanin, HIV-1 protease, Trypanosoma brucei brucei and yeast triosephosphate isomerases, and Escherichia coli trp aporepressor (but not trp repressor or the trp repressor/operator complex).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8003973 TI - The importance of anchorage in determining a strained protein loop conformation. AB - We examine the role of the conformational restriction imposed by constrained ends of a protein loop on the determination of a strained loop conformation. The Lys 116-Pro 117 peptide bond of staphylococcal nuclease A exists in equilibrium between the cis and trans isomers. The folded protein favors the strained cis isomer with an occupancy of 90%. This peptide bond is contained in a solvent exposed, flexible loop of residues 112-117 whose ends are anchored by Val 111 and Asn 118. Asn 118 is constrained by 2 side-chain hydrogen bonds. We investigate the importance of this constraint by replacing Asn 118 with aspartate, alanine, and glycine. We found that removing 1 or more of the hydrogen bonds observed in Asn 118 stabilizes the trans configuration over the cis configuration. By protonating the Asp 118 side chain of N118D through decreased pH, the hydrogen bonding character of Asp 118 approached that of Asn 118 in nuclease A, and the cis configuration was stabilized relative to the trans configuration. These data suggest that the rigid anchoring of the loop end is important in establishing the strained cis conformation. The segment of residues 112-117 in nuclease A provides a promising model system for study of the basic principles that determine polypeptide conformations. Such studies could be useful in the rational design or redesign of protein molecules. PMID- 8003974 TI - Analysis of protein transmembrane helical regions by a neural network. AB - Neural networks were used to generalize common themes found in transmembrane spanning protein helices. Various-sized databases were used containing nonoverlapping sequences, each 25 amino acids long. Training consisted of sorting these sequences into 1 of 2 groups: transmembrane helical peptides or nontransmembrane peptides. Learning was measured using a test set 10% the size of the training set. As training set size increased from 214 sequences to 1,751 sequences, learning increased in a nonlinear manner from 75% to a high of 98%, then declined to a low of 87%. The final training database consisted of roughly equal numbers of transmembrane (928) and nontransmembrane (1,018) sequences. All transmembrane sequences were entered into the database with respect to their lipid membrane orientation: from inside the membrane to outside. Generalized transmembrane helix and nontransmembrane peptides were constructed from the maximally weighted connecting strengths of fully trained networks. Four generalized transmembrane helices were found to contain 9 consensus residues: a K R-F triplet was found at the inside lipid interface, 2 isoleucine and 2 other phenylalanine residues were present in the helical body, and 2 tryptophan residues were found near the outside lipid interface. As a test of the training method, bacteriorhodopsin was examined to determine the position of its 7 transmembrane helices. PMID- 8003975 TI - De novo protein design using pairwise potentials and a genetic algorithm. AB - One of the major goals of molecular biology is to understand how protein chains fold into a unique 3-dimensional structure. Given this knowledge, perhaps the most exciting prospect will be the possibility of designing new proteins to perform designated tasks, an application that could prove to be of great importance in medicine and biotechnology. It is possible that effective protein design may be achieved without the requirement for a full understanding of the protein folding process. In this paper a simple method is described for designing an amino acid sequence to fit a given 3-dimensional structure. The compatibility of a designed sequence with a given fold is assessed by means of a set of statistically determined potentials (including interresidue pairwise and solvation terms), which have been previously applied to the problem of protein fold recognition. In order to generate sequences that best fit the fold, a genetic algorithm is used, whereby the sequence is optimized by a stochastic search in the style of natural selection. PMID- 8003976 TI - A proposal for a coherent mammalian histone H1 nomenclature correlated with amino acid sequences. AB - Bio-Rex 70 chromatography was combined with reverse-phase (RP) HPLC to fractionate histone H1 zero and 4 histone H1 subtypes from human placental nuclei as previously described (Parseghian MH et al., 1993, Chromosome Res 1:127-139). After proteolytic digestion of the subtypes with Staphylococcus aureus V8 protease, peptides were fractionated by RP-HPLC and partially sequenced by Edman degradation in order to correlate them with human spleen subtypes (Ohe Y, Hayashi H, Iwai K, 1986, J Biochem (Tokyo) 100:359-368; 1989, J Biochem (Tokyo) 106:844 857). Based on comparisons with the sequence data available from other mammalian species, subtypes were grouped. These groupings were used to construct a coherent nomenclature for mammalian somatic H1s. Homologous subtypes possess characteristic patterns of growth-related and cAMP-dependent phosphorylation sites. The groupings defined by amino acid sequence also were used to correlate the elution profiles and electrophoretic mobilities of subtypes derived from different species. Previous attempts at establishing an H1 nomenclature by chromatographic or electrophoretic fractionations has resulted in several misidentifications. We present here, for the first time, a nomenclature for somatic H1s based on amino acid sequences that are analogous to those for H1 zero and H1t. The groupings defined should be useful in correlating the many observations regarding H1 subtypes in the literature. PMID- 8003977 TI - Models of the serine protease domain of the human antithrombotic plasma factor activated protein C and its zymogen. AB - Three-dimensional structural analysis of physiologically important serine proteases is useful in identifying functional features relevant to the expression of their activities and specificities. The human serine protease anticoagulant protein C is currently the object of many genetic site-directed mutagenesis studies. Analyzing relationships between its structure and function and between naturally occurring mutations and their corresponding clinical phenotypes would be greatly assisted by a 3-dimensional structure of the enzyme. To this end, molecular models of the protease domain of protein C have been produced using computational techniques based on known crystal structures of homologous enzymes and on protein C functional information. The resultant models corresponding to different stages along the processing pathway of protein C were analyzed for structural and electrostatic differences arising during the process of protein C maturation and activation. The most satisfactory models included a calcium ion bound to residues homologous to those that ligate calcium in the trypsin structure. Inspection of the surface features of the models allowed identification of residues putatively involved in specific functional interactions. In particular, analysis of the electrostatic potential surface of the model delineated a positively charged region likely to represent a novel substrate recognition exosite. To assist with future mutational studies, binding of an octapeptide representing a protein C cleavage site of its substrate factor Va to the enzyme's active site region was modeled and analyzed. PMID- 8003978 TI - Isoprenyl diphosphate synthases: protein sequence comparisons, a phylogenetic tree, and predictions of secondary structure. AB - Isoprenyl diphosphate synthases are ubiquitous enzymes that catalyze the basic chain-elongation reaction in the isoprene biosynthetic pathway. Pairwise sequence comparisons were made for 6 farnesyl diphosphate synthases, 6 geranylgeranyl diphosphate synthases, and a hexaprenyl diphosphate synthase. Five regions with highly conserved residues, two of which contain aspartate-rich DDXX(XX)D motifs found in many prenyltransferases, were identified. A consensus secondary structure for the group, consisting mostly of alpha-helices, was predicted for the multiply aligned sequences from amino acid compositions, computer assignments of local structure, and hydropathy indices. Progressive sequence alignments suggest that the 13 isoprenyl diphosphate synthases evolved from a common ancestor into 3 distinct clusters. The most distant separation is between yeast hexaprenyl diphosphate synthetase and the other enzymes. Except for the chromoplastic geranylgeranyl diphosphate synthase from Capsicum annuum, the remaining farnesyl and geranylgeranyl diphosphate synthases segregate into prokaryotic/archaebacterial and eukaryotic families. PMID- 8003979 TI - DNA binding and bending by the transcription factors GAL4(62*) and GAL4(149*). AB - The DNA binding domain of the GAL4 transcription factor from yeast is located in the N-terminal 60 residues of the polypeptide of 881 amino acids. This domain binds 2 Zn ions, which form a binuclear cluster, Zn2C6, with 6 C residues, two of which bridge the 2 metal ions (Gardner KH et al., 1991, Biochemistry 30:11292 11302). Binding of Zn or Cd to GAL4 induces the conformation of the protein necessary to recognize the specific DNA sequence, UASG, to which GAL4 binds as a dimer. Gel retardation assays have been utilized to determine the relative affinities of the Zn2 and Zn1 forms of the N-terminal 149 residues of GAL4, GAL4(149*), for UASG DNA sequences. We show that Cd2- and Zn1GAL4(149*) bind to UASG DNA with 2-fold and 4-8-fold lower affinities than Zn2GAL4(149*), respectively. Thus, the metal species and the number of metal ions bound have measurable effects on the specific DNA binding affinity of GAL4, but these differences are small in comparison to the ratio, > 10(3) under some conditions, that characterizes the specific to nonspecific DNA binding affinities of the N terminal fragments of GAL4. A shorter N-terminal fragment, GAL4(62*), although it continues to recognize the UASG sequence with a high degree of specificity, binds with 1,000-2,000-fold lower affinity than does Zn2GAL4(149*). Gel retardation titrations of a DNA containing 2 UASG sites with increasing concentrations of GAL4(62*) generate a series of 4 retarded bands in contrast to 2 retarded bands formed when the same DNA is titrated with GAL4(149*). These data suggest that GAL4(62*) binds to the UASG sites as individual monomers that dimerize on the DNA, whereas GAL4(149*) binds the UASG DNA cooperatively as a dimer. The approximately 10(3) lower affinity of GAL4(62*) for the UASG DNA can be accounted for by its failure to form dimers in solution. Zn2-, Zn1-, or Cd2GAL4(149*) induces differential rates of gel migration in a series of circularly permutated UASG-containing DNA restriction fragments. Analysis of the data suggests that all 3 proteins cause a 26 degrees angle of bend in the DNA when bound to 1 UASG site and 45 degrees when bound to 2 tandem UASG sites. The same assay shows that GAL4(62*) does not induce significant bending of the UASG DNA sequences. Thus, the additional subdomains found in the larger polypeptide fragment, GAL4(149*), must exert an additional force on the DNA either through direct contacts with the DNA or indirectly through altered protein conformation. PMID- 8003980 TI - Heparin binding domain peptides of antithrombin III: analysis by isothermal titration calorimetry and circular dichroism spectroscopy. AB - The serine proteinase inhibitor antithrombin III (ATIII) is a key regulatory protein of intrinsic blood coagulation. ATIII attains its full biological activity only upon binding polysulfated oligosaccharides, such as heparin. A series of synthetic peptides have been prepared based on the proposed heparin binding regions of ATIII and their ability to bind heparin has been assessed by CD spectrometry, by isothermal titration calorimetry, and by the ability of the peptides to compete with ATIII for binding heparin in a factor Xa procoagulant enzyme assay. Peptide F123-G148, which encompasses both the purported high affinity pentasaccharide binding region and an adjacent, C-terminally directed segment of ATIII, was found to bind heparin with good affinity, but amino terminal truncations of this sequence, including L130-G148 and K136-G148 displayed attenuated heparin binding activities. In fact, K136-G148 appears to encompass only a low-affinity heparin binding site. In contrast, peptides based solely on the high-affinity binding site (K121-A134) displayed much higher affinities for heparin. By CD spectrometry, these high-affinity peptides are chiefly random coil in nature, but low microM concentrations of heparin induce significant alpha-helix conformation. K121-A134 also effectively competes with ATIII for binding heparin. Thus, through the use of synthetic peptides that encompass part, if not all, of the heparin binding site(s) within ATIII, we have further elucidated the structure-function relations of heparin-ATIII interactions. PMID- 8003981 TI - Distribution of distances between the tryptophan and the N-terminal residue of melittin in its complex with calmodulin, troponin C, and phospholipids. AB - We used frequency-domain measurements of fluorescence resonance energy transfer to measure the distribution of distances between Trp-19 of melittin and a 1 dimethylamino-5-sulfonylnaphthalene (dansyl) residue on the N-terminal-alpha amino group. Distance distributions were obtained for melittin free in solution and when complexed with calmodulin (CaM), troponin C (TnC), or palmitoyloleoyl-L alpha-phosphatidylcholine (POPC) vesicles. A wide range of donor (Trp-19)-to acceptor (dansyl) distances was found for free melittin, which is consistent with that expected for the random coil state, characterized by a Gaussian width (full width at half maxima) of 28.2 A. In contrast, narrow distance distributions were found for melittin complexed with CaM, 8.2 A, or with POPC vesicles, 4.9 A. A somewhat wider distribution was found for the melittin complex with TnC, 12.8 A, suggesting the presence of heterogeneity in the mode of binding between melittin and TnC. For all the complexes the mean Trp-19 to dansyl distance was near 20 A. This value is somewhat smaller than expected for the free alpha-helical state of melittin, suggesting that binding with CaM or TnC results in a modest decrease in the length of the melittin molecule. PMID- 8003982 TI - Slow-folding kinetics of ribonuclease-A by volume change and circular dichroism: evidence for two independent reactions. AB - The slow refolding of guanidine-HCl-denatured ribonuclease-A was studied by volume change and by kinetic CD at 222 and 276 nm. Dilatometric measurements revealed that on refolding there is a fast volume change of +232 mL/mol of protein. This is followed by a very slow nonexponential change that takes about 25 min to reach equilibrium. By adding varying amounts of (NH4)2SO4, the slow volume change curve was resolved into 2 concurrent reactions. The faster of the 2 slow events entails a negative volume change of -64 mL/mol of protein and appears to arise from proline isomerization. The slower process, attended by a positive change of +53 mL/mol of protein, has properties consistent with the "XY" reaction of Lin and Brands (1983, Biochemistry 22:563-573). This reaction is so named because the conformational nature of neither its initial (Y) nor its final state (X) is known; the transition is characterized solely by its absorbance and fluorescence kinetics. These are the first direct physical measures attributable to the "XY" process. The early formation of a compact structure in the event responsible for the rapid +232-mL/mol volume change, however, is consistent with the sequential model of folding (Cook KH, Schmid FX, Baldwin RL, 1979, Proc Natl Acad Sci USA 76:6157-6161; Kim PS, Baldwin RL, 1980, Biochemistry 19:6124-6129). The usefulness of volume change measurements as a method of detecting structural rearrangements was confirmed by finding agreement between time constants obtained from parallel volume change and kinetic CD experiments. The measured volume changes arise from both changes in hydration and changes in the packing of atoms in the interior of the protein. PMID- 8003984 TI - Thermodynamics of barnase unfolding. AB - The thermodynamics of barnase denaturation has been studied calorimetrically over a broad range of temperature and pH. It is shown that in acidic solutions the heat denaturation of barnase is well approximated by a 2-state transition. The heat denaturation of barnase proceeds with a significant increase of heat capacity, which determines the temperature dependencies of the enthalpy and entropy of its denaturation. The partial specific heat capacity of denatured barnase is very close to that expected for the completely unfolded protein. The specific denaturation enthalpy value extrapolated to 130 degrees C is also close to the value expected for the full unfolding. Therefore, the calorimetrically determined thermodynamic characteristics of barnase denaturation can be considered as characteristics of its complete unfolding and can be correlated with structural features--the number of hydrogen bonds, extent of van der Waals contacts, and the surface areas of polar and nonpolar groups. Using this information and thermodynamic information on transfer of protein groups into water, the contribution of various factors to the stabilization of the native structure of barnase has been estimated. The main contributors to the stabilization of the native state of barnase appear to be intramolecular hydrogen bonds. The contributions of van der Waals interactions between nonpolar groups and those of hydration effects of these groups are not as large if considered separately, but the combination of these 2 factors, known as hydrophobic interactions, is of the same order of magnitude as the contribution of hydrogen bonding. PMID- 8003983 TI - Protein folding dynamics: the diffusion-collision model and experimental data. AB - The diffusion-collision model of protein folding is assessed. A description is given of the qualitative aspects and quantitative results of the diffusion collision model and their relation to available experimental data. We consider alternative mechanisms for folding and point out their relationship to the diffusion-collision model. We show that the diffusion-collision model is supported by a growing body of experimental and theoretical evidence, and we outline future directions for developing the model and its applications. PMID- 8003986 TI - The three-dimensional profile method using residue preference as a continuous function of residue environment. AB - In the 3-dimensional profile method, the compatibility of an amino acid sequence for a given protein structure is scored as the sum of the preferences of the residues for their environments in the 3D structure. In the original method (Bowie JU, Luthy R, Eisenberg D, 1991, Science 253:164-170), residue environments were quantized into 18 discrete environmental classes. Here, amino acid residue preferences are expressed as a continuous function of environmental variables (residue area buried and fractional area buried by polar atoms). This continuous representation of residue preferences, expressed as a Fourier series, avoids the abrupt change of preference of residues in slightly different environments, as encountered in the original method with its 18 discrete environmental classes. When compared with the discrete 18-class representation of residue environments, this continuous 3D profile is found to be more sensitive in identifying sequences that fold into the profiled structure but share with it little sequence identity. The continuous 3D profile is also less sensitive to errors in environmental variables than is the discrete 3D profile. The continuous 3D profile can also be used to detect wrong folds or incorrectly modeled segments in an otherwise correct structure, as could the discrete 3D profile (Luthy R, Bowie JU, Eisenberg D, 1992, Nature 356:83-85). Moreover, the progress of structure improvement during atomic refinement can also be monitored by examining the profile scores in a moving-window scan. Finally, by defining a functional form for profile scores, we open the way to profile atomic refinement in which an atomic structure adjusts to produce residue environments more compatible with the protein side chains. PMID- 8003985 TI - Matrix-assisted laser desorption mass spectrometric peptide mapping of proteins separated by two-dimensional gel electrophoresis: determination of phosphorylation in synapsin I. AB - A technique is described for the rapid, sensitive analysis of posttranslational modifications of proteins that have been separated by 2-dimensional electrophoresis and blotted onto a membrane with a cationic surface. The isolated protein spots visualized by reverse staining of the blotting membrane are excised, washed, and subjected to chemical (cyanogen bromide) and/or enzymatic (endoproteinase Lys-C) degradation directly on the membrane. The resulting mixture of peptide fragments is extracted from the membrane into a solution that is compatible with matrix-assisted laser desorption mass spectrometric analysis and analyzed without fractionation. Relatively accurate (+/- 1 Da) mass determination of these peptide fragments provides a facile and sensitive means for detecting the presence of modifications and for correlating such modifications with the differential mobility of different isoforms of a given protein during 2-dimensional electrophoresis. The technique is applied to the determination of sites of phosphorylation in synapsins Ia and Ib, neuronal phosphoproteins that are believed to function in the regulation of neurotransmitter release and are substrates for cAMP and Ca2+/calmodulin dependent protein kinases, which appear to control their biological activity. PMID- 8003987 TI - Interaction of phlorizin, a potent inhibitor of the Na+/D-glucose cotransporter, with the NADPH-binding site of mammalian catalases. AB - Phlorizin is a reversible inhibitor of the renal and small intestinal Na+/D glucose cotransporter. In an attempt to purify the Na+/D-glucose cotransporter from a pig kidney brush border membrane fraction, we used an Affi-Gel affinity chromatography column to which 3-aminophlorizin had been coupled. A protein, composed according to crosslinking experiments of at least 3 subunits of molecular weight 60 kDa, was found to bind specifically to the phlorizin column. This protein was subsequently identified as catalase by sequence homology of three of its tryptic fragments to the sequence of several mammalian catalases as well as by its enzymatic activity. Although bovine liver catalase was bound tightly to the affinity matrix, phlorizin had no effect on the ability of the enzyme to degrade H2O2. In contrast, the Aspergillus niger and Neurospora crassa catalases did not bind to the phlorizin column. This difference may be related to the fact that mammalian catalases, but not the fungal catalases, contain an NADPH binding site with a yet unknown function. Interestingly, bovine liver catalase could be eluted with 50 microM NADPH from phlorizin columns. Irradiation in the presence of [3H]4-azidophlorizin allowed photolabeling of bovine liver catalase, which was prevented by the presence of 10 microM NADPH. After digestion of photolabeled catalase with chymotrypsin, a radioactive peptide was detected that was absent in catalase protected with NADPH. Docking simulations suggested that phlorizin can bind to the NADPH binding site with high affinity. PMID- 8003988 TI - Similarity between pyridoxal/pyridoxamine phosphate-dependent enzymes involved in dideoxy and deoxyaminosugar biosynthesis and other pyridoxal phosphate enzymes. AB - A multiple sequence alignment among aspartate aminotransferase, dialkylglycine decarboxylase, and serine hydroxymethyltransferase (DAS) was used for profile databank search. The DAS profile could detect similarities to other pyridoxal or pyridoxamine phosphate-dependent enzymes, like several gene products involved in dideoxysugar and deoxyaminosugar synthesis. The alignment among DAS and such gene products shows the conservation of aspartate 222 and lysine 258, which, in aspartate aminotransferase, interacts with the N1 of the coenzyme pyridine ring and forms the internal Schiff base, respectively. The lysine is replaced by histidine in the pyridoxamine phosphate-dependent gene products. The alignment indicates also that the region encompassing the coenzyme binding site is the most conserved. PMID- 8003989 TI - A structural basis for the interaction of urea with lysozyme. AB - The effect of urea on the crystal structure of hen egg-white lysozyme has been investigated using X-ray crystallography. High resolution structures have been determined from crystals grown in the presence of 0, 0.7, 2, 3, 4, and 5 M urea and from crystals soaked in 9 M urea. All the forms are essentially isomorphous with the native type II crystals, and the derived structures exhibit excellent geometry and RMS differences from ideality in bond distances and angles. Comparison of the urea complex structures with the native enzyme (type II form, at 1.5 A resolution) indicates that the effect of urea is minimal over the concentration range studied. The mean difference in backbone conformation between the native enzyme and its urea complexes varies from 0.18 to 0.49 A. Conformational changes are limited to flexible surface loops (Thr 69-Asn 74, Ser 100-Asn 103), the active site loop (Asn 59-Cys 80), and the C-terminus (Cys 127 Leu 129). Urea molecules are bound to distinct sites on the surface of the protein. One molecule is bound to the active site cleft's C subsite, at all concentrations, in a fashion analogous to that of the N-acetyl substituent of substrate and inhibitor sugars normally bound to this site. Occupation of this subsite by urea alone does not appear to induce the conformational changes associated with inhibitor binding. PMID- 8003990 TI - Charge reversal at the P3' position in protein C optimally enhances thrombin affinity and activation rate. AB - We have examined the properties of several human protein C (HPC) derivatives with substitutions for acidic residues near the thrombin cleavage site, including changing the P3' Asp to Asn (D172N), Gly (D172G), Ala (D172A), or Lys (D172K). The rate of thrombin-catalyzed activation of D172N, D172G, and D172A was increased 4-9-fold compared to wild-type HPC, primarily due to a reduction in the inhibitory effect of calcium and a resulting increase in affinity for free alpha thrombin. There was no significant increase in activation rate or affinity with these 3 derivatives in the absence of calcium, confirming that P3' Asp affects calcium dependency in the native protein C molecule. With charge reversal at P3' (D172K), there was a 30-fold increase in activation rate in the presence of calcium, but unlike the other derivatives, there was a substantial effect (5 fold) on the activation rate and affinity for free alpha-thrombin in the absence of calcium. Thus, protein C affinity for thrombin appears to be influenced by a combination of calcium-dependent and -independent effects of the acidic P3' residue. PMID- 8003991 TI - Getting the most from your consulting dollar. PMID- 8003992 TI - Self-directed teams: your role. PMID- 8003993 TI - Assisting with career changes in nursing. PMID- 8003994 TI - Computer-based ACLS training: one year's experience with Actronics. PMID- 8003995 TI - Staying focused on staff development outcomes. PMID- 8003996 TI - Tina's tips to shift and stretch. Interview by Janet Mackin. PMID- 8003997 TI - Not the same old boring lecture. PMID- 8003998 TI - Spend a day with a nurse. PMID- 8003999 TI - AHCPR guidelines are a basis for research and funding. PMID- 8004001 TI - How to successfully propose a computer-assisted learning lab in a shared governance setting. PMID- 8004002 TI - Outcome evaluations for clinical classes. PMID- 8004000 TI - Ideas for celebrating National Nurses Week. PMID- 8004004 TI - Four lessons on self-directed learning. PMID- 8004003 TI - Prep tips for a JCAHO survey on competency. PMID- 8004005 TI - Write right now: a commitment, an idea, a plan. PMID- 8004006 TI - MAP kinase kinase: a node connecting multiple pathways. AB - Numerous studies have been published these last few years on the involvement of MAP kinases in signal transduction reflecting their importance in cell cycle and cell growth controls. The identification and the characterization of their direct upstream activator has considerably enlarged our understanding of the phosphorylation network. The MAP kinase kinases (MAPKKs) are dual-specificity protein kinases which phosphorylate and activate MAP kinases. To date, MAPKK homologues have been found in yeast, invertebrates, amphibians, and mammals. Moreover, the MAPKK/MAPK phosphorylation switch constitutes a basic module activated in distinct pathways in yeast and in vertebrates. MAPKK regulation studies have led to the discovery of at least four MAPKK convergent pathways in higher organisms. One of these is similar to the yeast pheromone response pathway which includes the ste11 protein kinase. Two other pathways require the activation of either one or both of the serine/threonine kinase-encoded oncogenes c-Raf-1 and c-Mos. Additionally, recent studies suggest a possible effect of the cell cycle control regulator cyclin-dependent kinase 1 (cdc2) on MAPKK activity. Finally, MAPKKs seem to be essential transducers through which signals must pass before reaching the nucleus. PMID- 8004007 TI - Endocytosis and intracellular degradation of heterologous protein by eosinophilic granulocytes isolated from rainbow trout (Oncorhynchus mykiss) posterior intestine. AB - Adherence capacity to tissue substrate, endocytosis capacity for heterologous and homologous proteins, and proteolytic activity were determined in intestinal granulocytes (EGCs) isolated from healthy adult rainbow trout. The percentage of cells that could adhere to a smooth plastic surface increased with increasing incubation time. Endocytosis was effective for heterologous (human immunoglobulin G, IgGh; ovine somatotropin, oST) but not homologous proteins (recombinant trout somatotropin, rtST). The activity of cathepsin D increased significantly after the endocytosis of a heterologous protein. Finally, the analysis of immunoblots of homogenates of granulocytes incubated in the presence of the two different proteins was used to show the endocytosis and degradation of heterologous proteins. These results show that isolated EGCs can endocytose and degrade heterologous proteins. PMID- 8004008 TI - Detection on liver tissue sections of S-phase markers in synchronized cycling rat hepatocytes by SIMS microscopy. AB - The aim of this study was to localise two ionic S-phase markers in tissue sections using SIMS microscopy: aluminium as a potential endogenous marker and bromine as an exogenous marker after in vivo injection of bromodeoxyuridine (BrdU). This study was performed in an experimental model of hyperplastic proliferation after partial hepatectomy in rat. Aluminium was never detected in nuclei which were positive or negative for tritiated thymidine uptake, as determined by autoradiography in tissue prepared by cryotechniques. In contrast, bromine of BrdU was found in hepatocyte nuclei. However, there was a discrepancy between SIMS bromine images and BrdU immunohistochemistry detection which appears more sensitive. This is probably due to problems of stereology intrinsic to the correlation method which requires serial sections for this multi-instrumental approach. PMID- 8004009 TI - The development and evolution of actin-containing organelles during spermiogenesis of a primitive nematode. AB - Spermatogenesis in the primitive marine nematode Sphaerolaimus hirsutus (Chromadoria, Sphaerolaimidae) was investigated by examining the ultrastructure and cytochemistry. Spermatozoa are lenticular cells of about 15 microns in diameter and are devoid of flagellum and acrosome as in other nematodes. In spermatocytes, dictyosomes produced transient structures, the fibrous body membranous organelle complexes (FB-MO). In spermatids, the FBs were arranged as cartwheel spokes, with the FBs in the centre and the MOs at the periphery. The FBs were first made up of parallel fibres and surrounded by a membrane, then, in a later stage, showed a dense central structure with a surrounding vermiculate region and were devoid of membrane. The FBs contain actin as shown by immunofluorescence using a monoclonal anti-actin antibody and by affinity cytochemistry using fluorescent phalloidin. MOs contained mainly F-actin as shown by their labelling by phalloidin. In spermatozoa, the MOs were no longer peripheral but arranged on a ring in the central region of the cell and the FBs disappeared to form the cytoskeleton of the cell outer region. It was assumed, by analogy with the ultrastructure of other nematodes, that this cytoskeleton was made up of major-sperm-protein (MSP). Labelling of spermatids of Caenorhabditis elegans also revealed the presence of actin, but cells and actin spots were very small. This demonstrates the interest of Sphaerolaimus as a giant sperm model in which fibrous bodies and membranous organelles can be distinguished. In the few species in which it has been studied (C elegans and Ascaris suum), MSP is thought to constitute in spermatozoa a motile cytoskeleton excluding the presence of actin. However, the present study of Sphaerolaimus shows that the actin cytoskeleton is present during nematode spermiogenesis. PMID- 8004011 TI - Comparison of techniques for the assessment of polymorphonuclear leukocyte polarisation in suspension. AB - Polarisation of polymorphonuclear leukocytes (PMN) in suspension was assessed using three techniques: 1) visual classification; 2) computerised morphometry; and 3) flow cytometry. While visual classification detected the formation, polarisation and type of cytoplasmic extensions produced by PMN, morphometry and flow cytometry detected only the formation of extensions. The area, perimeter and ellipticity were, in general, statistically different for each subtype of PMN shape identified by visual classification. Furthermore, the magnitude and direction of changes detected by flow cytometry were affected by the use of erythrocyte lysis (during isolation of the cells) and the fixative used prior to analysis. The findings of this study demonstrate that visual classification is a more sensitive, reliable and appropriate assay of PMN polarisation than current morphometric and flow cytometric methods. PMID- 8004012 TI - Localization and partial characterization of a rat ovarian granulosa cell protein with a monoclonal antibody. AB - Hybridoma cell lines were obtained from mouse splenocytes sensitized to granulosa cells collected from rat ovaries after gonadotropin stimulation. A monoclonal antibody (5G5) was obtained which reacted with granulosa cells and showed a positive reaction with serum-free conditioned medium containing granulosa cell secreted proteins. Immunoblotting of the conditioned medium and light- and electron-microscopic immunocytochemistry of rat ovary show that mAb 5G5 is directed against a 59-kDa protein which is located on the plasma membrane of granulosa cells. Furthermore, the immunoreactivity of the granulosa cells depends both on the degree of follicle development and on the position of the granulosa cells within the follicles. Strong immunoreactivity was observed in the innermost granulosa cell layers, close to the oocyte and the antral cavity. The results obtained show that mAb 5G5 is a useful marker of a 59-kDa granulosa cell protein which might be of importance for the development of the follicle and the oocyte maturation. PMID- 8004010 TI - Phosphoinositidase C isozymes in SaOS-2 cells: immunocytochemical detection in nuclear and cytoplasmic compartments. AB - SaOS-2 cell line presents osteoblastic characteristics which can be modulated by specific agonists involving also phosphoinositide breakdown. In order to determine whether SaOS-2 cells display a phosphoinositide signalling system not only at the cytosol-cell membrane level but also, as recently reported for other cell lines, at the nuclear level, a study has been performed to evaluate the phosphoinositidase C (PIC) activity and to localize different isoforms of PIC in nuclear and cytoplasmic compartments. By immunochemicals methods, and by confocal and electron microscope immunocytochemistry, both PIC beta 1 and gamma 1 have been detected in the nucleus, while only PIC gamma 1 was found in the cytoplasm. A specific association with the inner nuclear matrix has been demonstrated for PIC beta 1 and gamma 1; this latter resulted, on the other hand, in relationship with cytoskeletal filaments after high salt extraction. These findings suggest that these enzymes are not completely soluble but functionally related with cytoskeletal and nucleoskeletal structures. PMID- 8004014 TI - Animating the curriculum: integrating multimedia into teaching. AB - At many medical schools, the medical library assists faculty in finding and integrating new technology into the classroom, student laboratories, and lecture or small group sessions. Libraries also provide faculty with a place to do development. This paper recounts the author's experience creating software-based educational materials. In the process of creating the Slice of Life videodisc and developing and distributing other medical education software, techniques that do and do not work in producing multimedia for medical education became evident. Use of multimedia features and new modalities not possible with books, rather than development of electronic versions of texts and atlases, should be emphasized. Important human factors include collaboration, continuity, evaluation, and sharing of equipment, software, code, effort, expertise, and experiences. Distribution and technical support also are important activities in which medical libraries can participate. PMID- 8004013 TI - Comparative evolution of endocytosis levels and of the cell surface area during the L929 cell cycle: a fluorescence study with TMA-DPH. AB - 1-[4-(trimethylamino)phenyl]-6-phenylhexa-1,3,5-triene (TMA-DPH), a membrane fluorescence probe, interacts with living cells by instantaneous partition between the external medium and the plasma membrane, where it becomes fluorescent. The corresponding fluorescence intensity is then proportional to the cell surface. On the other hand, once incorporated into the plasma membrane, TMA DPH follows this membrane in the constitutive intracellular traffic and behaves as a monitor for endocytosis. Using this tool on L929 synchronized cells, we showed that the endocytosis levels after 30 min uptake of the probe increased from G1 to mitosis, when they abruptly decreased. The cell surface remained constant throughout the cell cycle, except at the beginning of mitosis when it almost doubled. PMID- 8004015 TI - Developing a medical informatics education program to support a statewide health information network. AB - The Florida Health Information Network (FHIN) was established in October 1989 to provide biomedical information services to the University of Florida Health Science Center (HSC) and to health professionals throughout the state--especially the northern thirty-nine counties of the state. FHIN services are available to all affiliates of the HSC and by annual subscription to nonaffiliates. At present, FHIN services include database access, circulation services, document delivery, and information services. Training network users has been an objective since the inception. Training has targeted both the HSC Library staff and HSC users and now is expanding to include remote users. Because many users have had insufficient experience with computers, the library has to teach the mechanics of access and network use and to instruct users regarding applications and database searching. This paper describes the development and implementation of the medical informatics education program. Topics include library staff training; educational offerings for HSC faculty, staff, and students; development and implementation of the remote training program; and organizational and budgetary implications for the construction of such a program. PMID- 8004017 TI - DocuShock: options for document delivery in the nineties. Introduction. PMID- 8004016 TI - Traumatic brain injury information database: a user survey. AB - A major challenge facing individuals with brain injury and the rehabilitation professionals who assist them is the acquisition of current, understandable information. Health professionals in hospitals usually provide initial information, which patients with brain injury and their families often find inadequate. They then find it necessary to seek information from independent sources. One such source, TBI-INFO, an information dissemination service, conducted a survey to determine how effectively it was satisfying consumer and professional demands. Responses generally indicated that the acquisition of information improved patients' integration into the community and enhanced their understanding of brain injury and its effects. Most of the information respondents received was new to them, most shared the information with others, and may requested information more than once. Half of the respondents changed their approach to a specific situation as a result of information they received. These results show that independent sources are capable of providing information that improves the perceived quality of life for individuals with traumatic brain injury. PMID- 8004018 TI - Electronic document delivery using the Internet. AB - The Health Sciences Libraries Consortium (HSLC) was established in 1985 by thirteen founding member institutions in Pennsylvania and Delaware. In 1989, the Interlibrary Loan, Document Delivery, and Union List Task Force, appointed by the HSLC Board of Directors, successfully demonstrated the feasibility of supplying 94% of all interlibrary loan (ILL) photocopy requests in forty-eight hours or less by a network application of group 3-level memory telefacsimiles. However, the expenses associated with the telefacsimile operation and the limitations associated with network polling protocols challenged participants to seek new alternatives for ILL. In 1990, the HSLC introduced HSLC HealthNET, an online wide area network linking eleven of the thirteen institutions and their resources while providing access to the Internet. The HSLC HealthNET additionally supports a centralized shared library system, several locally mounted databases, and consortiumwide electronic mail. In 1991, a project was initiated to evaluate Ariel software, pioneered by the Research Libraries Group (RLG), compared to the existing network application of group 3-level telefacsimiles. Factors identified as critical to Ariel's potential to replace the telefacsimile network were the proprietary software specifications for Internet access, the use of HSLC's existing wide-area network (WAN), and a hardware platform that was optimal for an ILL environment. This article describes the Ariel project history, the transition to Ariel from the telefacsimile network, evaluation of equipment features for processing efficiency, and operational issues affecting ILL policy. PMID- 8004019 TI - Faxon Finder/Faxon Xpress: report from a beta test site. AB - In this environment of expanding information needs, spiraling journal costs, and curtailed financial resources, medical libraries must take advantage of the rapid evolution in document delivery services. There are exciting developments in transmission technology, from fax machines to scanners to the Internet. There is also a notable shift away from the traditional reliance on library networks toward use of commercial vendors as document providers. These changes require reevaluation of interlibrary loan (ILL) and document delivery systems on many levels, including pricing structures, work flow, and impact on collection development. As commercial vendors develop increasingly effective products, librarians can test, evaluate, and incorporate them into their ILL operations to enhance service to users and relieve the pressure to acquire new resources; in this way, librarians can move from the "just in case" practice of building an on site collection to the "just in time" model of providing timely delivery of materials to users as needed. This paper describes a beta test of the Faxon Finder/Faxon Xpress table of contents and document delivery services conducted by the Treadwell Library of the Massachusetts General Hospital. PMID- 8004020 TI - SAIL: automating interlibrary loan. AB - The National Library of Medicine (NLM) initiated the System for Automated Interlibrary Loan (SAIL) pilot project to study the feasibility of using imaging technology linked to the DOCLINE system to deliver copies of journal articles. During the project, NLM converted a small number of print journal issues to electronic form, linking the captured articles to the MEDLINE citation unique identifier. DOCLINE requests for these journals that could not be filled by network libraries were routed to SAIL. Nearly 23,000 articles from sixty-four journals recently selected for indexing in Index Medicus were scanned to convert them to electronic images. During fiscal year 1992, 4,586 scanned articles were used to fill 10,444 interlibrary loan (ILL) requests, and more than half of these were used only once. Eighty percent of all the articles were not requested at all. The total cost per article delivered was $10.76, substantially more than it costs to process a photocopy request. Because conversion costs were the major component of the total SAIL cost, and most of the articles captured for the project were not requested, this model was not cost-effective. Data on SAIL journal article use was compared with all ILL requests filled by NLM for the same period. Eighty-eight percent of all articles requested from NLM were requested only once. The results of the SAIL project demonstrated that converting journal articles to electronic images and storing them in anticipation of repeated requests would not meet NLM's objective to improve interlibrary loan. PMID- 8004022 TI - UnCover: the article access solution. AB - The current climate for academic libraries is such that traditional collection development philosophies are being examined anew. The rising cost of journals, coupled with steady or declining budgets, has necessitated a review of the means for providing access to information at the local level. Where once the local collection was all-important, the focus now has shifted in other directions. As Leach describes it, libraries will begin to shift collection development funds to document delivery services. Instead of purchasing resources "just in case," the new paradigm may be purchasing information "just in time". Anticipating this shift and taking advantage of existing technologies, the UnCover Company has developed a service that, although relatively new, has been widely discussed. PMID- 8004021 TI - A look at LOANSOME DOC service. AB - The Pacific Southwest Regional Medical Library (PSRML) launched a project in 1988 to assess the feasibility of electronic linkages between health professionals using GRATEFUL MED--the National Library of Medicine's (NLM) software program for searching the MEDLARS databases--and libraries using DOCLINE, NLM's automated interlibrary loan request-and-referral system. This paper describes the origins of LOANSOME DOC and initial usage experiences. Results of the LOANSOME DOC beta test, including usage statistics, are reported. The paper also describes the mechanics of nationwide implementation of LOANSOME DOC, including guidelines used by the Regional Medical Libraries (RMLs) to refer unaffiliated health professionals to DOCLINE libraries for LOANSOME DOC service. National usage statistics for the first full year of implementation (October 1, 1991, to September 30, 1992) are provided, and user satisfaction surveys conducted in 1993 by two RMLs are examined. Future enhancements to LOANSOME DOC are suggested. PMID- 8004023 TI - Legal considerations for document delivery services. AB - Health sciences libraries that provide fee-based information services must consider and develop policies and procedures for complying with legal requirements. This paper reviews the provisions of copyright law that pertain to document delivery, including two court decisions concerning copyright. Also discussed are recent actions by publishers to reinforce their view of libraries' responsibilities for royalty fees for articles copied and their use of licenses to impose additional restrictions on the use of and reproduction of materials. PMID- 8004024 TI - Assessment of physicians' information needs in five Texas counties. AB - In 1990, a questionnaire was mailed to all physicians in four counties in the lower Rio Grande Valley of Texas and to a random sample of physicians in Bexar County, Texas (San Antonio). Two hundred and eighty of 573 Valley physicians (48.9%) and 162 of 273 Bexar County physicians (59.3%) responded to the survey, for an overall response rate of 52.2%. The two groups were compared primarily to determine differences between physicians who have access to established medical libraries and physicians who practice in remote areas without local access to medical information. Demographic variables, professional practice characteristics, and patient characteristics were compared. Information resource use, particularly reasons for use and non-use of MEDLINE, was explored. Questions also were asked about the availability of various types of information technology. The results indicated that differences in the health care profile did not affect the information usage of the physicians but that differences did exist between the two groups in the use of MEDLINE and libraries. There was no statistically significant difference in either group's rating of experience with using databases, with more than 40% in each group rating themselves as not at all experienced. PMID- 8004025 TI - Information needs of rural health care practitioners in Hawaii. AB - Rural health care workers need a wide range of specialized information but have difficulties locating and accessing information resources. The information needs of Hawaii's rural health care practitioners and their methods of accessing information were studied through interviews and mailed questionnaires. The following barriers to information access were identified: lack of funds, inadequate hardware, infrastructure problems, and insufficient knowledge about information sources and how to use them. Although many (85%) reported having computers, only a minority (30%) have modems, and even fewer use online resources or the free electronic databases at public and university libraries. Most reported that journal articles were the information source that best met their needs and that personal files or a colleague's collection were the most common places for accessing needed materials. Recommendations for solving some of the information problems include development of a State of Hawaii rural health information clearinghouse; better identification, training, and use of available services; and, most importantly, the establishment of rural health care information agents (modeled on agriculture extension agents) on each major island. PMID- 8004026 TI - GRATEFUL MED-LOANSOME DOC outreach project in central Pennsylvania. AB - The Geisinger Medical Center Library implemented a GRATEFUL MED outreach project in rural north-central Pennsylvania directed at providing physicians access to current medical literature. A total of 1,327 physicians affiliated with twenty three hospitals practice in a thirteen-county area the size of the state of New Jersey. Of these hospitals, only four have hospital libraries, which vary in size and in staff abilities to meet the information needs of their affiliated physicians. The outreach project encompassed two stages--demonstrations of GRATEFUL MED and LOANSOME DOC at county medical society or hospital meetings, and installation and training in individual offices. The eighteen-month project ended in March 1992. Statistics were collected for the number of GRATEFUL MED software packages loaded (sixty-two), the number of document delivery items supplied by Geisinger Medical Center Library to project participants (367), and the number of physicians attending introductory demonstrations or follow-up training programs (455 at sixty-eight sessions). By the end of the project, 147 (32%) of those who had attended a seminar had access to GRATEFUL MED. PMID- 8004027 TI - A comparison of CINAHL and MEDLINE CD-ROM in four allied health areas. PMID- 8004028 TI - Work sampling in a one-person library. PMID- 8004029 TI - Hospital utilization and library search requests: is there a link? PMID- 8004030 TI - GRATEFUL MED and the need for outreach programs. PMID- 8004031 TI - Response to "Information needs of the rural physician". PMID- 8004032 TI - Citation patterns in the health sciences: a response. PMID- 8004033 TI - Our international interests--a reprise. PMID- 8004034 TI - Contribution of "in vitro" assays to preclinical and premarketing testing in immunotoxicology. AB - An attempt to replace the "in vivo" testing by "in vitro" exposure of cells to drugs is discussed from the point of view of the limitations of these artificial test conditions. The critical reminders are evaluated, the most important ones being the pharmacokinetics, pharmacodynamics and metabolism of drugs in the body what may be a cause of the discrepancy between "in vivo" and "in vitro" exposure assays. Various sensitivity of different cell types and of different phases of the generation cycle represent the crucial importance in the immune response and in the drug-cell interactions. The "in vitro" assays are technically sophisticated and mostly based on the tissue-culture techniques. However, both in immunology and immunotoxicology standardization, validation and usage of rules of Good Laboratory Practice are required. Finally, possibilities and contribution of "in vitro" assays to immunotoxicology are listed. It is apparent that for establishment of common rules these studies require intensive international and interlaboratory cooperation and coordination. PMID- 8004035 TI - TOCOEN Project--goals, state and prospects. PMID- 8004036 TI - Chemical ecotoxicology--general aspects. AB - Chemical ecotoxicology is defined as application of methods of chemistry to the study of the occurrence and adverse effects of anthropogenic chemicals and their transformation products in the biosphere. Examples of methods and their applications are given. PMID- 8004037 TI - Determination of polycyclic aromates, chlorinated insecticides and polychlorinated biphenyls in the air of north Bohemian region. AB - North Bohemia is recognized to be one of the most polluted areas in Europe. Combustion processes in several power plants, other industrial activities, transportation, waste incineration and household furnaces belong to the main sources of the air pollution. Therefore, the presence of numerous organic pollutants, namely polycyclic aromates (PAHs), chlorinated insecticides and polychlorinated biphenyls (PCBs) is expected to contribute significantly to the impaired health conditions. Samples of the ambient air collected in different seasons were analysed using GC-ECD, GC-MS and HPLC methods. Chlorinated insecticides and PCBs have been found of minor importance with concentrations laying below 0.1 ng/m3 and 1.0 ng/m3 respectively. Among PAHs, phenanthrene, fluoranthene and pyrene have been the major components. Concentrations of PAHs found during heating period have been about 10 times higher than those observed in the late spring. The role of household furnaces and motor vehicles in production of compounds is discussed. PMID- 8004038 TI - Occurrence and leaching of polycyclic aromatic hydrocarbons (PAH) generated at steelworks. PMID- 8004039 TI - Occurrence of organic pollutants in the soil of upper Austria. AB - In the course of a study of soil quality over 200 soil samples were collected in an Austrian province and analyzed for residues of organochlorine pesticides, selected PCB congeners, triazine herbicides and selected polycyclic aromatic hydrocarbons. Concentrations of these compounds were found to vary within a broad range. This holds true especially for polycyclic aromatic hydrocarbons. The results are set into relation to the agricultural use of soils, the intensity of nearby road traffic and population density. PMID- 8004040 TI - Indicator parameters for PCDD/F as a possible means to monitor emissions of toxicity equivalents from waste incinerators. AB - In the stack emissions from a hazardous waste incinerator we found highly significant correlations between 2,3,7,8-tetrachlorodibenzo-p-dioxin toxicity equivalents (I-TE) and pentachlorobenzene (CI5Bz) and between I-TE and heptachlorobiphenyl (CI7B). We therefore propose to utilize these substances as indicator parameters from which I-TE values can be estimated. Since they are easier to analyze than PCDD/F the use of indicator parameters such as CI5Bz and CI7B offers the chance to monitor I-TE emissions which are limited to 0.1 ng/m3 in many European countries. PMID- 8004041 TI - Patterns of polynuclear aromatic hydrocarbons (PAH) in sediments. AB - The patterns of polynuclear aromatic hydrocarbons (PAH) in sediments were studied by Principal Component Analysis (PCA). Phenanthrene (P), fluoranthene (Fl), pyrene (Py), benzo[a]anthracene (BaA), chrysene (Chr), and benzo[a]pyrene (BaP) were used. Three patterns were found: type P, associated primarily with petroleum hydrocarbons, type Fl, from relatively clean marine sediments, and type Py+BaA+Chr+BaP, from industrialized areas. Aerial fallout appears to be the major source of PAH for the latter. There is a considerable variation in the PAH patterns obtained in different laboratories. PCA is a good tool for the study of PAH patterns. PMID- 8004042 TI - Indoor air quality: a risk-based approach to health criteria for radon indoors. Summary report on a WHO Working Group Eilat, Israel, 28 March-4 April 1993. AB - The Working Group discussed to what extent exposure to radon is a public health risk. It reviewed data from epidemiological studies of the occupational exposure of miners and residential exposures, animal experiments and other relevant work. The Group confirmed radon to be a human carcinogen, and recommended that indoor situations where individual risks exceeded 10(-3) per year should always be considered severe, further risk reduction must be sought based on procedures such as the optimization and evaluation of available control techniques. The Group considered what guidance could be offered to national authorities, and whether risks from radon should be considered solely within the present radiation protection framework policies or be handled as a part of a more integrated framework of all environmental risks; a three-step management scheme was proposed. The Group then discussed the problem of risk communication as a part of assisting policy-makers to arrive at strategies best suited to their socioeconomic conditions. The report concludes with 22 recommendations. PMID- 8004043 TI - National project of health restoration and promotion in the Czech Republic. PMID- 8004044 TI - Water-borne household infections due to Mycobacterium xenopi. AB - Of 21 M. xenopi excretors recorded in Prague in 1990, 13 suffered from a serious pulmonary disease and the organisms were detected repeatedly in all of them. In 11 flats of these excretors water samples were collected from faucets and showers and M. xenopi was detected in five of them, as well as in five neighbouring flats. In flats of six remaining excretors and 12 adjoining flats, M. xenopi was not found. However, in 14 of 28 examined flats, the clinically insignificant M. gordonae was isolated. Water samples from three water-works, six regional water reservoirs and 10 street hydrants did not harbour mycobacteria. In the authors' view M. xenopi originating from infected drinking water outlets may cause infections in exposed household dwellers. PMID- 8004045 TI - Electron microscopy and the polymerase chain reaction of spirochetes from the blood of patients with Lyme disease. AB - Results of studies using direct antigen detection suggest that seronegative Lyme borreliosis is not rare and support the hypothesis that Borrelia antigens can persist in humans. We report three successful cultures from blood out of 30 attempts from 96 Lyme disease patients. The proof of borreliaemia in early or late phases of Lyme disease by immuno-capture electron microscopy has practical importance for subsequent cultivation. The polymerase chain reaction with oligonucleotide sequences directed against 16S rRNA identified two of our blood isolates as Borrelia burgdorferi genospecies III., VS 461 group, and one as Borrelia garinii sp. nov. All of the three isolates were reactive with monoclonal antibody H9724 against flagellin and with antibody against main extracellular protein at 83 kDa. Borrelia garinii had a single predominant protein OspA at 33.5 kDa and reacted with monoclonal antibody H5332 in contrast to two isolates of the VS 461 group with two major proteins OspA and OspB at 32.5 and 35 kDa. We conclude that isolation of spirochetes from the blood might prove successful in clinically selected cases of Lyme borreliosis. Immuno-capture electron microscopy has proved to be a sensitive assay for monitoring and studying Lyme borreliosis. PMID- 8004046 TI - Health risk assessment of the mycotoxin ochratoxin A to humans: Czech Republic- Brno--1991/92. AB - In the course of year 1991 and 1992 about 594 blood donors of the Brno agglomeration in the Czech Republic were examined for the ochratoxin A content (OA) in blood serum. When higher concentrations of OA were found the blood donors were examined repeatedly (differentiation of acute or chronic exposure). A mean concentration of 0.63 microgram OA/l blood serum (0.30 microgram = geom.mean) was recorded. The assessed continuous mean daily dietary intake of OA was about 0.74 ng (0.35 ng = geom. mean) OA/kg b.w./day. The assessed continuous mean contamination of food groups (cereal and meat products) was about 0.65 microgram (0.31 microgram = geom. mean) OA/kg. In persons with elevated OA concentrations in blood serum the decrease was at the latest confirmed within 2 months after the test result. An accidental acute exposure was probably involved. Tolerable daily intake of OA (TDI) was determined with regard to the nephrotoxic, teratogenic, immunosuppressive and carcinogenic effect at the level of: 16,500, 250 and 5 ng OA/kg b.w./day. As a legislative limit TDI = 5 ng OA/kg b.w./day was suggested. The group of persons studied was probably not threatened by any of the health risks given. PMID- 8004047 TI - Trachoma, an imported disease. AB - The authors review the incidence of trachoma in the Czech Republic during the last 20 years. Trachoma has become almost exclusively an imported disease. In 1989-1990 the authors treated 34 foreign nationals with imported trachoma at the Infectious Diseases Clinic in Prague. Even after many years' stay in the Czech Republic foreigners may develop exacerbations of the trachomatous process. PMID- 8004048 TI - In vitro inhibition of some gram-positive bacteria by Staphylococci and Aerococcus viridans of porcine origin. AB - Nine coagulase-negative Staphylococci and Aerococcus viridans were tested for bacterial antagonism. Seven of the nine of the coagulase-negative Staphylococci and Aerococcus viridans inhibited the growth of four Staph. hyicus, three Staph. aureus strains and some other Gram-positive bacteria, including Streptococcus group A and D, Corynebacteria, but none of the Gram-negative and yeast was inhibited on agar media. There was also production of inhibitory substances in different types of liquid media but no antagonistic activity was observed on Millipore membrane. The inhibition was not due to the pH change of media in which the producers were grown, but due to production of inhibitory substances tentatively classed as antibiotics. PMID- 8004049 TI - Biomechanical concerns with fixed partial dentures involving implants. AB - Nine biomechanical factors involved in the design and fabrication of fixed partial dentures incorporating implants are discussed, focusing upon the deleterious effects of leverage, torsion, occlusal overload, and poor oral hygiene. Areas of concern are cantilevers, pier abutments, excessive fixed spans, use and misuse of nonrigid connectors, off-axis loading, occlusal plane to implant height ratio, inadequate support, distribution, and mandibular flexion and torsion. PMID- 8004050 TI - Department of Veterans Affairs Cooperative Studies Project number 147: level of examiner reliability over seven years. AB - In 1980 the Veterans Administration Cooperative Studies Program No. 147 initiated a multicenter, multidisciplinary clinical study to evaluate the use of alternative alloys for porcelain-fused-to-metal restorations. An investigation of interexaminer agreement was conducted after seven years utilizing three measures of reliability: percentage of exact agreement using a five-point scale, percentage of agreement using a dichotomous (satisfactory-unsatisfactory) scale, and [kappa], a statistic which is intended to measure agreement beyond what would be expected to occur by chance. Exact agreement on the five-point scale ranged from 77 to 99 percent. Percent agreement on the dichotomous scale was above 99 percent for all of the criteria. Kappa ranged from 0.56 to 0.91, indicating moderate to near perfect agreement among examiners. Reliability of the study evaluations reinforced the validity and significance of the findings. PMID- 8004051 TI - Technique for standardization of panoramic radiographs using helium-neon laser guided positioning. AB - A limitation of the use of panoramic radiography in implant dentistry has been variations in patient positioning, which can produce dissimilar radiographs and is a serious problem in longitudinal investigations. Previous techniques to standardize panoramic radiographs have been cumbersome and technique sensitive. Bilateral helium-neon lasers were mounted on two-axis micrometer translation stages and projected as cross-hairs on a phantom skull. The cross-point of each pattern was superimposed on a facial soft tissue landmark on either side of the skull. Laser coordinates were recorded and an initial radiograph was produced for each of three experimental groups. Two investigators repeated radiographs for each group six times using the original settings. The radiographs were digitized and the variance calculated and compared using a video digital analysis program. Repeat radiographs were compared to the originals by superimposing each pair and measuring the variance in radiographic markers. The variance ranged from 0.1 to 2.2 mm with the experimental groups and from 2.5 to 38.7 mm with the control group. Repeated measures analysis of variance showed no statistical significance (P > 0.125) among each of the experimental groups using the laser system and a significant difference (P < 0.001) when the control group is included in the analysis. Variance for experimental groups was not significant between the examiners (P > 0.45). A laser repositioning system may have application in implant dentistry by standardizing panoramic radiographs for comparisons in long term investigations. PMID- 8004052 TI - Composite bone graft augmentation for maxillary implant reconstruction: clinical report. AB - A method for antral augmentation with a composite graft of freshly harvested iliac crest bone marrow and porous hydroxyapatite for implant placement is described. The volume, cellular type, particulate composition, and density of the graft permit rapid implant placement and integration when compared with totally synthetic grafting procedures. A clinical report is presented. PMID- 8004053 TI - Histomorphometry of initial bone healing around zirconium implants in rats. AB - Histometric evaluations as a function of time were performed with zirconium implants during the healing period in 10 Wistar rats. The implants (7 mm x 1 mm x 0.1 mm) were placed in the right tibia of the animals. Five rats were killed after 14 days and the remainder were sacrificed 30 days after implantation. The tibiae were resected, radiographed, and embedded in poly(methyl methacrylate). Three cross-sections were obtained transverse to the major axis of each tibia. Osseointegrated tissue thickness, percentage of direct bone-to-implant contact, and osseointegrated tissue volume were evaluated for each specimen. Bone formation was observed on the surface of the implanted strip that was in contact with tibia marrow. This method is proposed for the evaluation of the first stage of healing of bone in contact with different implant materials subjected to various surface treatment. PMID- 8004055 TI - Efficient production of active and mutated ADP-ribosyltransferase (S1) of pertussis toxin using affinity expression cassette polymerase chain reaction. AB - We describe an efficient, general approach for cloning, expression and purification of heterologous proteins in Escherichia coli host strains. The affinity expression cassette polymerase chain reaction (AEC-PCR) allows the insertion of virtually any coding sequence in suitable expression vectors. For ease of purification of the (over)produced protein the gene expression cassettes are engineered by specifically designed oligonucleotide primers in the polymerase chain reaction (PCR) to contain either 3' or 5' additional nucleotides coding for a short amino acid sequence constituting an 'affinity block' fused to either end of the protein. This allows a one-step purification by affinity chromatography. In combination with PCR-mediated site-specific mutagenesis this approach is a highly efficient way for the expression and isolation of proteins and for the analysis and dissection of functional domains. The application of AEC-PCR is demonstrated by the cloning, production and purification of the native, active and the mutagenized, inactive ADP-ribosyltransferase (S1 subunit) of pertussis toxin. In this example, a string of six histidines has been engineered to either the N-terminal or the C-terminal end of the protein to serve as 'affinity block' for the isolation of the recombinant protein by immobilized metal ion affinity chromatography (IMAC). Thus, the S1 subunit can now be produced in sufficient quantities to facilitate further studies on its immunological and molecular properties. PMID- 8004054 TI - Protection of mice against Clostridium chauvoei infection by anti-idiotype antibody to a monoclonal antibody to flagella. AB - Polyclonal rabbit anti-idiotypic antibody (anti-Id) against the protective monoclonal antibody specific to the flagella of Clostridium chauvoei was produced, purified, and characterized. Anti-Id inhibited the binding of its related monoclonal antibody to the flagellar antigen, suggesting that the anti-Id bore an internal image of the flagellar antigen. When mice were immunized with anti-Id intraperitoneally, the survival rate increased significantly, compared with mice immunized with normal rabbit IgG (P < 0.01), and specific anti flagellar antibodies were induced. PMID- 8004056 TI - Immunological properties and ganglioside recognitions by Campylobacter jejuni enterotoxin and cholera toxin. AB - The immunological properties of Campylobacter jejuni enterotoxin (CJT) and cholera toxin (CT) were compared by enzyme-linked immunosorbent assay (ELISA) and Western blotting analysis with antiserum against each toxin. Antibody against CJT recognized the 68, 54 and 43 kDa polypeptides of CJT and the 11 kDa subunit of CT, whereas antibody against CT recognized the 68 and 54 kDa polypeptides of CJT and 11 kDa subunit of CT. The immunological reactions between the heterogeneous combinations of toxins and the antibodies were weaker than those between the homogenous systems. Thus, different antigenicity was found in CJT and CT at the subunit level, although they possessed cross-reactive epitope(s). The binding of CJT and CT to gangliosides was also examined. CJT and CT bound to GM1 ganglioside preferentially than to other ganglioside species. However, CJT did not bind to GD1b in spite of the fact that CT preferred GD1b. This suggests that both toxins recognize different receptors on the surface of the target cell. This study is the first demonstration of the different properties between CJT and CT in immunological character and ganglioside recognition. PMID- 8004057 TI - Immunochemical study of polysaccharide antigen in Streptococcus sobrinus and Streptococcus downei with a cross-reactive monoclonal antibody. AB - A monoclonal antibody (mAb h-448) was prepared after cell fusion of mouse myeloma cells (SP2/0-Ag-14) to the spleen cells of mice immunised with serotype h strain (MF25) of Streptococcus downei. The antibody (IgM class) reacted in enzyme immunoassay only with whole cells as well as purified polysaccharide (PS) antigen of Streptococcus sobrinus (types d and g) and Streptococcus downei (serotype h), but not with cells or purified PS antigen from any other serotypes of the mutans group of streptococci. mAb h-448 also quantitatively precipitated in solution with the purified antigens. Competitive hapten inhibition tests demonstrated that beta-methylgalactopyranoside inhibited the reaction most strongly. Although rhamnose also showed a substantial inhibitory effect, the results of this study indicate that the antigenic determinant of the PS antigen has a structure similar to the beta-methylgalactopyranoside molecule. PMID- 8004058 TI - Viral antibodies in infectious mononucleosis. AB - Patients with Epstein-Barr virus (EBV) infectious mononucleosis (IM) usually develop heterophilic antibodies and some autoantibodies. Antibodies to rubella, measles, adeno-, entero-, herpes simplex, cytomegalo- and varicella-zoster viruses were titrated in sera from IM patients and matched healthy controls using the complement fixation test (CFT) and the haemagglutination inhibition test. Except for herpes simplex virus and cytomegalovirus, the IM sera had significantly higher arithmetical and geometrical mean antibody titres and showed in most cases higher antibody prevalences in the CFT. The titre rise was most pronounced for rubella and measles antibodies, between 2- and 3-fold. There were no cases of very high titres occasionally seen in IM. The IM sera had higher total IgG serum levels than the controls, 17.27 g/l and 11.8 g/l, respectively (P < 0.001). The present data show that in addition to previously reported high levels of some autoantibodies and of heterophilic antibodies, there is a more general increase in IgG antibodies to commonly occurring viruses. This increase is most likely due to the polyclonal activation of B-lymphocytes following the binding of EBV to the complement receptor CR2 (CD21). When due consideration is given to the possible occasional occurrence of a false positive rubella IgM test, the raised antibody-titres will most likely not interfere with routine diagnostics. PMID- 8004059 TI - Differential release of tumor necrosis factor-alpha from murine peritoneal macrophages stimulated with virulent and avirulent species of mycobacteria. AB - The ability of Mycobacterium tuberculosis H37Rv and H37Ra, M. bovis BCG and M. smegmatis to induce the secretion of tumor necrosis factor-alpha (TNF-alpha) by cultured murine peritoneal macrophages is inversely related to their virulence. The avirulent species of mycobacteria which were unable to persist in macrophages were capable of inducing significant levels of TNF-alpha compared to that formed in cultures infected with the virulent M. tuberculosis H37Rv. This difference was also associated with an inherent toxicity by live H37Rv for macrophage cultures. Heat-killed H37Rv was non-toxic and induced significant levels of TNF-alpha; in contrast, live and heat-killed suspensions of avirulent mycobacteria had an equivalent ability to trigger TNF-alpha secretion. The TNF-alpha response was dose-dependent, related directly to the percentage of infected cells, and peaked 6-12 h post-infection. An early and vigorous TNF-alpha response appears to be a marker of macrophage resistance, while the downregulation of this response seems associated with macrophage toxicity and unrestricted mycobacterial growth. PMID- 8004060 TI - Cytokine expression by inflammatory neutrophils. AB - Bloodstream neutrophils do not express mRNA for interleukin-1 beta (IL-1 beta), but transcripts for this cytokine are rapidly induced following exposure to recombinant granulocyte-macrophage colony-stimulating factor (rGM-CSF) in vitro. Levels of IL-1 beta mRNA reach maximal values 1 h after exposure to rGM-CSF and then decline to near basal levels by 4 h. Similarly, rGM-CSF treatment of blood neutrophils in vitro induced increases in levels of mRNA for IL-6 and tumour necrosis factor-alpha (TNF-alpha). RNA extracted from neutrophils isolated from the synovial fluid of patients with rheumatoid arthritis expressed low, but significant levels of IL-1 beta mRNA that were between 0.5 and 3% of the levels that could be maximally induced by rGM-CSF treatment of blood neutrophils. However, transcripts for TNF-alpha and IL-6 were not detected in these synovial fluid neutrophils. mRNA for transforming growth factor-beta (TGF-beta) was constitutively expressed in blood and synovial fluid neutrophils and transcripts for this cytokine were not altered by rGM-CSF exposure. Because of the transient nature of IL-1 beta expression by activated neutrophils, we propose that the low levels of expression of mRNA for this cytokine in the synovial fluid neutrophils represents expression by a small, perhaps newly-recruited and activated, sub population of cells. IL-1 beta expression by this sub-population may thus contribute to the pathogenesis of rheumatoid disease. PMID- 8004061 TI - Effects of anaesthetics on membrane mobility and locomotor responses of human neutrophils. AB - The morphological response of neutrophils to chemotactic factors is characterized by an immediate change (in seconds) from a spherical to an irregular shape. Within two or three minutes, the cells assume the head-tail polarity typical of locomotor cells. In this study the effects of the anaesthetic drugs, propofol and thiopentone, on the time-sequence of the morphological response of human neutrophils to the chemotactic peptide fMet-Leu-Phe were examined. At concentrations seen in the plasma during anaesthesia, both drugs inhibited both the rate and degree of the neutrophil chemotactic response. The effect of propofol was not attributable to its lipid vehicle, as 10% intralipid alone had no effect on neutrophil polarization. Plasma membrane reorganization occurs during polarization of neutrophils, resulting in morphological and functional changes which prepare the cells for chemotaxis and phagocytosis. Fluorescence recovery after photobleaching (FRAP) was used to investigate effects of the anaesthetics on membrane lipid behaviour. With a lipid probe, the proportion of mobile lipid in neutrophils exposed to propofol or thiopentone was reduced. There was a less significant reduction with intralipid which also caused reduction in velocity of lateral diffusion of the probe. These findings suggest that the inhibitory effects of anaesthetics on neutrophil locomotion are related to reductions in fluid mobility of the plasma membranes of anaesthetic-treated cells. PMID- 8004062 TI - Stimulation of reactive oxidant production in neutrophils by soluble and insoluble immune complexes occurs via different receptors/signal transduction systems. AB - Cell-free synovial fluid from patients with rheumatoid arthritis contains soluble and insoluble IgG-containing immune complexes which activate reactive oxidant production in human neutrophils. In this report we have measured the effects of inhibitors of signal transduction pathways on neutrophil activation by these complexes and also following activation by synthetic soluble and insoluble immune complexes made from human serum albumin (HSA) and anti-(HSA) antibodies. In all aspects studied, the soluble rheumatoid complexes and the soluble synthetic complexes were indistinguishable in the ways in which they activated neutrophils. Activation of reactive oxidant production in response to these soluble complexes was completely inhibited by pertussis toxin (indicating G-protein coupling of receptor occupancy), completely insensitive to staurosporine (indicating that oxidant production did not require protein kinase C activity), only marginally (< 30%) inhibited by butanol (indicating that dependence upon activity of phospholipase D was minimal), and completely inhibited by chloracysine, an inhibitor of phospholipase A2. In contrast, activation of reactive oxidant production in response to the insoluble rheumatoid or insoluble synthetic immune complexes was largely pertussis toxin insensitive, inhibited by > 50% by staurosporine, inhibited by > 50% by butanol, and completely inhibited by chloracysine. These results show that the receptor-mediated signal transduction systems activated by the soluble and insoluble immune complexes are different. Because the soluble complexes activate a transient burst of reactive oxidant secretion from primed neutrophils, the mechanisms regulating either the release or the intracellular production of oxidants within rheumatoid joints are distinct and hence may be pharmacologically modified independently of each other. PMID- 8004063 TI - Tracheobronchial washings from seven vertebrate species as growth media for the four species of Bordetella. AB - The four species of Bordetella differed in their ability to grow at 37 degrees C in membrane-filtered tracheobronchial washings (TBW) from seven vertebrate species, including their natural hosts. From washed inocula of approximately 2 x 10(3) colony-forming units per ml (cfu ml-1), Bordetella bronchiseptica and B. avium grew much better than the other two bordetellae and yielded stationary phase cultures containing 10(8)-10(9) cfu ml-1 in most of the TBW samples. These counts were only moderately lower than those attained in CL medium which contains about a 450-times higher concentration of amino acids. B. bronchiseptica and B. avium also grew to a limited extent in phosphate-buffered saline without nutrient supplements. B. parapertussis grew in TBW from man, sheep, rabbit, mouse and chicken, but not in TBW from a dog and a horse or in PBS. B. pertussis grew well in CL medium, but not in PBS or in any of 13 samples of TBW from the seven vertebrate species, which included three samples of lung lavage fluid from human patients. Analysis of the TBW samples for known Bordetella nutrients revealed concentrations of amino acids and nicotinic acid averaging 0.35 mM and 0.56 microgram ml-1 respectively. PMID- 8004064 TI - Effect of lysophosphatidic acid on motility, polarisation and metabolic burst of human neutrophils. AB - The effect of lysophosphatidic acid (LPA) on human neutrophil activation was examined by a combination of automated tracking assays, cell shape measurements and assays of the metabolic burst by means of 7-dimethylamino-naphthalene-1,2 dicarbonic acid hydrazide (DNDH)-dependent chemiluminescence. LPA powerfully stimulated polarisation and motility. Polarisation became detectable at 2 microM LPA and virtually 100% of cells were polarised at 20 microM LPA. Cell motility increased with the degree of polarisation, and was diminished at high LPA concentration, but this decrease was reversed by albumin. LPA also inhibited the metabolic burst response to both n-formyl-methionyl-leucyl-phenylalanine (fMLP) and phorobol 12-myristate 13-acetate (PMA). Inhibition of the PMA-induced metabolic burst by LPA was not affected by pertussis toxin, showing that the effect was not mediated by the pertussis toxin-sensitive heterotrimeric G protein, and that inhibition of the PMA-stimulated metabolic burst by LPA could result from a direct action of LPA on the small cytosolic GTP-binding proteins. These results indicate that lysophosphatidic acid production by thrombin activated platelets could play a significant role in the regulation of the inflammatory response. PMID- 8004065 TI - Giving shape to shadows. PMID- 8004066 TI - Architect of her own living. PMID- 8004067 TI - Danger: stress at work. PMID- 8004068 TI - Long-term planning for care. PMID- 8004069 TI - A touching story. PMID- 8004070 TI - Patient-controlled analgesia. PMID- 8004071 TI - ACE on health. PMID- 8004072 TI - Issues in FOCUS. PMID- 8004073 TI - Catalysts for change. PMID- 8004074 TI - Kalymnos: island of care. PMID- 8004076 TI - Fair and equal access. PMID- 8004075 TI - As I was saying... PMID- 8004077 TI - Respite care. PMID- 8004078 TI - Families and rehabilitation. PMID- 8004079 TI - Primary caregivers' psychological status and family functioning after traumatic brain injury. AB - This study investigated the prevalence of psychological distress and unhealthy family functioning among primary caregivers of 62 adult outpatients with traumatic brain injury, using the Brief Symptom Inventory (BSI) and the Family Assessment Device (FAD). Approximately half of the caregivers reported elevated distress as indicated by scores on the BSI General Stress Index. Elevations on the Anxiety scale were evident among one-third of the sample, and one-fourth demonstrated elevations on the Depression subscale. Elevated scores on the Paranoid Ideation and Psychoticism scales suggested that feelings of burden and alienation were commonly reported. As indicated by the FAD, caregivers showed greater levels of unhealthy functioning relative to published norms for non patient and medical patient samples, but showed better functioning than psychiatric samples. Spouses were significantly more likely to report elevated depression scores compared to parents. There was also a trend for spouses to report greater unhealthy family functioning than parents. Findings are consistent with those reported by European researchers. Experience indicates that the BSI and FAD are potentially valuable clinical and research tools. PMID- 8004080 TI - Patient correlates of caregivers' distress and family functioning after traumatic brain injury. AB - This study examined the relationship of patient variables to caregiver distress and family functioning after TBI in 62 families. An extension of Kreutzer et al. 1994 (in press), the present investigation used four categories of predictor variables: indices of injury severity, neuropsychological tests, neurobehavioural problem checklist scales, and kinship of caregiver (i.e. spouse vs. parent). Caregiver distress and family functioning were measured by the Brief Symptom Inventory (BSI) and Family Assessment Device (FAD), respectively. Regression analyses revealed that indices of injury severity did not predict BSI scores. Time post-injury predicted several FAD subscales. The number of the patient's neurobehavioural problems predicted BSI subscale scores most consistently, particularly the Global Severity Index, Somatic, Obsessive-Compulsive and Depression scales. Scores on the behaviour problem subscale predicted BSI scores better than other kinds of problems, and also had some relation to several FAD subscales. Of the 10 neuropsychological test scores, those which measured verbal abilities were more predictive of caregiver's BSI scores. Kinship (i.e. being a spouse) predicted Depression scores, even when other variables were partialled out. Research findings are integrated with European studies and clinical implications for understanding caregiver distress are discussed. PMID- 8004081 TI - Day of injury CT scan as an index to pre-injury brain morphology. AB - This study compared the ventricle-to-brain ratio (VBR) of the day-of-injury (DOI) computerized tomogram (CT) in traumatic brain-injured (TBI) patients with post injury (2 months or greater) magnetic resonance (MR) VBRs in the same patients and in medical control subjects. The DOI VBR did not differ significantly from the medical controls, but both (DOI and medical control VBR) differed significantly from post-injury VBR. Additionally, a case study is presented wherein MR imaging studies were obtained prior to TBI so that a direct comparison of pre-injury to DOI to post-injury changes could be made. In this case the pre injury and DOI VBRs were within approximately 9% of each other. In contrast, the post-injury VBR demonstrated over a 100% increase in comparison to either the pre injury or DOI scan. This case and another case are illustrated using three dimensional image analysis to represent ventricular change over time. These cases, along with the similarity of the DOI VBR with the medical controls, suggests that the DOI VBR can be utilized as an estimate or index of pre-injury ventricle/brain morphology. This will permit the use of DOI CT data for within subject designs in TBI research that examines the course of degenerative changes over time. PMID- 8004082 TI - Follow-up studies of somatosensory evoked potentials and auditory brainstem evoked potentials in patients with post-coma unawareness (PCU) of traumatic brain injury. AB - Some patients who suffer severe traumatic brain injury (TBI) fail to recover higher brain functions in spite of giving the appearance of sleep-wake cycles. Such a state is called post-coma unawareness (PCU) and varies in type and degree. Patients may remain in this state for months or even years. This study focused on the follow-up of upper-limb somatosensory evoked potential (USEP) measurements and auditory brainstem responses (ABR), with an emphasis on dynamic changes, in 10 patients with PCU resulting from TBI. The prognostic value of USEP and ABR was evaluated. Results showed that the presence of ABR in PCU patients had no prognostic value, because ABRs were found both in patients who recovered and those who did not, even a year after the trauma. The presence of normal ABR in PCU patients may suggest that the brainstem has been spared in the pathoanatomy of the PCU condition, with the significant damage occurring above this level, in cortical and subcortical (that is, hemispheral) areas. USEP was graded using the new system of Houlden [1] for 'acute' comatose patients. It was found that USEP measurements had some prognostic value in PCU patients. Most of the patients who remained in the PCU state had grade 2 or less initially, whereas most of the patients who later recovered or achieved at least a 'reduced life' state were grade 4 or more. On initial testing (when all patients were still in the PCU state), defined cortical potential (mainly in the slope of the building NI potential) was seen in only some of the patients who later recovered.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8004083 TI - Mild pediatric traumatic brain injury: adjusting significance levels for multiple comparisons. AB - The outcome following mild traumatic brain injury (TBI) is controversial. We addressed this topic in a study of neurobehavioural and 'real-world' functioning among 53 children with mild TBI and their matched controls, using statistical methods recently developed for multiple comparisons. Because the study involved calculation of 414 p-values, four methods of adjustment for multiple comparisons, including the Bonferroni method, were used to avoid 'false-positive' statistical significance. The additional three methods allowed greater insight into the data than provided by the standard Bonferroni adjustment. Results showed that at initial testing, three areas of 'real-world' functioning (eating, domestic and home/community living skills) had weak but statistically significant associations with mild injury. No other specific areas of neuro-behavioural or 'real-world' functioning had plausible associations with the injury either initially, at 1 year, or when changes over the year were considered. However, the adjustment for multiple comparisons provided additional results. There were statistical significant associations of the injury with the entire domain of neurobehavioural variables both initially and at 1 year. These results suggest that the injury affects a spectrum of neurobehavioural skills weakly, rather than a single area substantially. The gain from using multiple comparison methods is discussed. PMID- 8004084 TI - Social cognitive factors in brain injury-associated personality change. AB - Often social difficulties are the most enduring difficulties after a head injury. The social deficits most frequently reported by relatives 6-12 months post-injury include egocentric styles of social interaction characterized by family members as a change in the head-injured patient's personality style. The described characteristics of head-injured patients in terms of social perspective-taking abilities are similar to those of children reported in the cognitive developmental literature. To demonstrate the nature of the social deficits in head-injured participants, social perspective-taking paradigms in the development literature were used to construct a task to be administered to both head-injured and non-head-injured adults. Results of the comparison between the two groups suggest deficits in social perspective-taking abilities in head-injured adults similar to the level demonstrated by pre-adolescent children. PMID- 8004085 TI - Whatever happened after the 'return from silence'? AB - A case is presented of a child who, following unexpected rapid recovery of functional communication skills 9 months post-severe closed head injury, continued to progress in speech and language skills even 4 years post-injury. Although the child did not recover to premorbid levels of functioning, her recovery over such a protracted period proved quite remarkable. The case is considered in the light of recent findings on the recovery of linguistic skills subsequent to childhood closed head injury. PMID- 8004086 TI - Neuropsychological toxicology of methylene diphenyl diisocyanate: a report of five cases. AB - The neuropsychological functioning of five men suffering alleged physical, cognitive and behavioural changes following exposure to methylene diphenyl diisocyanate (MDI), an industrial chemical, was investigated in the present study. At the time of assessment, four of the five patients remained symptomatic despite having no contact with MDI for periods ranging from 5 to 9 months. All patients reported experiencing subjective symptoms consisting of respiratory distress, headaches, depression, irritability, forgetfulness, decreased calculating ability, word-finding problems and reduced concentration. While the pattern of neuropsychological deficits varied among the patients, common findings for the group included intact psychomotor, psychosensory, visuographic and language functions accompanied by deceased concentration, mental efficiency, rate of information processing, learning ability and abstract reasoning. All five patients also revealed significant emotional distress on an objective personality measure. In general, the neuropsychological test data support the presence of behavioural and cognitive correlates of CNS injury following exposure to MDI. PMID- 8004087 TI - Two autosomal dominant neuropathies result from reciprocal DNA duplication/deletion of a region on chromosome 17. AB - Charcot-Marie-Tooth disease type 1A (CMT1A) is a common autosomal dominant demyelinating neuropathy that is associated with a 1.5 megabase (Mb) tandem DNA duplication in chromosome 17p11.2-p12. Hereditary neuropathy with liability to pressure palsies (HNPP, tomaculous neuropathy) is another less frequently diagnosed autosomal dominant neuropathy and is associated with a 1.5 Mb deletion in chromosome 17p11.2-12. Meiotic unequal crossover is a proposed mechanism for the generation of both the duplication in CMT1A and the deletion in HNPP. CMT1A REP is a repeat that flanks the region which is duplicated/deleted in CMT1A/HNPP. The CMT1A-REP repeat sequence may mediate unequal crossover through misalignment of the homologous, repeated sequences. Three copies of the CMT1A-REP repeat are present on stably inherited CMT1A duplication chromosomes. In this report, molecular analysis in multiple patients detected three copies of the CMT1A-REP sequence on both inherited and de novo CMT1A duplication chromosomes, and one copy of the CMT1A-REP repeat on the deleted chromosome in both inherited and de novo HNPP. These observations support the hypothesis that a reciprocal recombination mechanism involving the CMT1A-REP is responsible for the generation of both the duplicated and deleted chromosomes, and document the first examples in humans of Mendelian syndromes resulting from the reciprocal products of unequal exchange involving large intra-chromosomal segments. PMID- 8004088 TI - Olfactory receptor gene cluster on human chromosome 17: possible duplication of an ancestral receptor repertoire. AB - A gene superfamily of olfactory receptors (ORs) has recently been identified in a number of species. These receptors share a seven transmembrane domain structure with many neurotransmitter and hormone receptors, and are likely to underlie the recognition and G-protein-mediated transduction of odorant signals. Previously, OR genes cloned in different species were from random locations in the respective genomes. We report here the cloning of 16 human OR genes, all from chromosome 17 (17p13.3). The intronless coding regions are physically mapped (on 35 cosmids) in one 0.35Mb long contiguous cluster, with an average intergenic separation of 15kb. The human OR genes in the cluster belong to four different gene subfamilies, displaying as much sequence variability as any randomly selected group of ORs. This suggests that the cluster identified may be one of several copies of an ancestral OR gene repertoire whose existence may predate the divergence of mammals. The latter may have duplicated in some species to form the present mammalian OR gene repertoire, with several hundred genes. The human chromosome 17 OR gene cluster may thus be a good model for understanding human olfaction, as well as the ontogeny and phylogeny of the OR gene superfamily. PMID- 8004089 TI - Isolation of yeast artificial chromosome clones from 54 polymorphic loci mapped with high odds on human chromosome 4. AB - We constructed a yeast artificial chromosome (YAC) framework map of human chromosome 4 by screening a YAC library with 63 polymorphic DNA markers located on the chromosome. These genetic markers are from two framework meiotic maps that had previously been constructed by two research groups, and are placed on the two maps with odds for their order of 1000:1 or greater. In addition to isolating and determining the sizes of 141 YAC clones for 54 of these markers, we combined the two framework meiotic maps to produce a single integrated map. These combined maps and the YAC clones provide a set of extended DNA loci ordered at high odds that can be used to isolate additional polymorphic loci and genes, and to serve as a framework for obtaining a higher resolution physical map of the chromosome. PMID- 8004090 TI - Molecular and phenotypic mapping of the short arm of chromosome 5: sublocalization of the critical region for the cri-du-chat syndrome. AB - Forty-nine individuals have been identified with deletions or translocations involving the short arm of chromosome 5. While most display the classical phenotype of the cri-du-chat syndrome, several of the patients do not have the syndrome or have only a subset of the clinical features. Somatic cell hybrids containing the deleted chromosome 5 were derived from each patient. Each somatic cell hybrid was analyzed at the DNA level using 136 chromosome 5p-specific DNA fragments. It was possible to unambiguously order most of the chromosomal breakpoints present in the somatic cell hybrids based on the hybridization patterns of Southern blots. Further comparisons between the deletions present in the patients and their clinical features identified several chromosomal regions that were involved in specific clinical features. A critical chromosomal region involved the high-pitched cry mapped to 5p15.3, while the chromosomal region involved in the remaining features of the cri-du-chat syndrome mapped to a small region within 5p15.2. Deletions that did not include these two chromosomal regions presented varying clinical phenotypes from severe mental retardation and microcephaly to a clinically normal phenotype. These results demonstrate the need for careful characterization of a 5p deletion in prenatal cases before clinical predictions are made. PMID- 8004091 TI - Instability of simple sequence repeats in a mammalian cell line. AB - Short tandem repeat sequences in the mammalian genome are considered to be unstable, since many of them are polymorphic in length; however, the extent of this instability has been difficult to quantitate. We have directly determined the rate of mutation of a simple sequence repeat in a mammalian cell line. A plasmid containing a dinucleotide repeat [poly(CA/GT)] that disrupts the reading frame of a downstream gene was integrated into the genome of a mouse cell line, and spontaneous revertants were selected. Reversion rates were more than 100 times higher in cells carrying the repeated sequence than in control cells that carried the same fusion gene with a 4-bp out-of-frame deletion. Revertant clones derived from the lines carrying the dinucleotide repeat had insertions or deletions of one or more repeat units. PMID- 8004092 TI - Identification of a gene from Xp21 with similarity to the tctex-1 gene of the murine t complex. AB - Long range physical mapping within the p21 region of the X chromosome identified a CpG rich island approximately 180 kb centromeric to the chronic granulomatous disease (CGD) locus. The segments adjacent to the CpG island hybridized to discrete bands in DNAs of several species and when used to screen retinal cDNA libraries led to the identification of cDNAs that detected a mRNA of 2.1 kb in many tissues. Molecular characterization of corresponding genomic clones of this novel human gene confirmed the origin of the cDNA clones and indicated a genomic structure with five exons spanning a total of 9 kb. The complete cDNA sequence revealed that this gene contained a putative open reading frame of 116 amino acids with a 3' untranslated region of 1.74 kb. The amino acid sequence shows a high degree of similarity to the predicted product of the tctex-1 gene of the mouse t complex. As linkage studies and patients with deletions have implicated the Xp21 region as containing the retinitis pigmentosa defect (RP3), the gene was assessed as a candidate disease gene in RP3 families. A single base pair polymorphism was identified within the coding region but no disease associated changes were found by single strand conformational polymorphism and sequencing analysis of amplified exons of 20 RP patients. Analysis of a dinucleotide repeat polymorphism within this gene in families affected with RP3 suggested refinement of the RP3 region. PMID- 8004093 TI - The gene responsible for adrenoleukodystrophy encodes a peroxisomal membrane protein. AB - Adrenoleukodystrophy is a severe genetic demyelinating disease associated with an impairment of beta-oxidation of very long chain fatty acids (VLCFA) in peroxisomes. Earlier studies had suggested that a deficiency in VLCFA CoA synthetase was the primary defect. A candidate adrenoleukodystrophy gene has recently been cloned and was found unexpectedly to encode a putative ATP-binding cassette transporter. We have raised monoclonal antibodies against this protein, that detect a 75kDa band. This protein was absent in several patients with adrenoleukodystrophy. Immunofluorescence and immunoelectron microscopy showed that the adrenoleukodystrophy protein (ALDP) is associated with the peroxisomal membrane. Distinct immunofluorescence patterns were observed in cell lines from patients with Zellweger syndrome (a peroxisomal biogenesis disorder) belonging to different complementation groups. PMID- 8004094 TI - The gene for the familial form of incontinentia pigmenti (IP2) maps to the distal part of Xq28. AB - Linkage data for familial incontinentia pigmenti (IP2) and 17 X chromosomal markers are reported. The linkage previously found between IP2 and the F8C locus is confirmed (Z max = 11.85 at theta = 0.028). Linkage is established with distal markers DXS1108 (Z max = 10.06 at theta = 0.00) and DXYS154 (Z = 9.07 at theta = 0.019). Multipoint analysis supports the distal localization of the IP2 gene with respect to the F8C locus. PMID- 8004095 TI - Activation of the gamma E-crystallin pseudogene in the human hereditary Coppock like cataract. AB - The locus for the hereditary human Coppock-like cataract (CCL) is closely linked to a particular combination of polymorphic TaqI sites within the human gamma crystallin gene cluster. Mapping of these sites shows that they define a 15 kb region encompassing the gamma D and psi gamma E gene. The gamma D and the psi gamma E gene were cloned from the CCL chromosome and characterized. The gamma D gene was functionally equivalent to its allele cloned from a wild-type chromosome. The CCL psi gamma E gene contains a cluster of sequence changes within and around its TATA box. Together these cause a ten-fold increase in the activity of the psi gamma E promoter, raising the level of expression of this gene to 30% of that of the gamma D gene. The predicted protein product of the psi gamma E gene is a 6 kD N-terminal gamma-crystallin fragment. Reactivation of the psi gamma E gene and concomitant overexpression of the gamma-crystallin fragment could be the cause of the Coppock-like cataract. PMID- 8004096 TI - Mapping of a chromosome 15 region involved in limb girdle muscular dystrophy. AB - A gene responsible for an autosomal recessive form of limb girdle muscular dystrophy (LGMD2, MIM number 253600) has been localized on chromosome 15. After genotyping additional markers of this chromosome, two were found to flank the disease locus within an interval that was assessed as 7 centiMorgans. The screening of the CEPH YAC libraries with the corresponding probes allowed the isolation of YACs which were used in fluorescence in situ hybridization to define the LGMD2 cytogenetic interval as 15q15.1-15q21.1. Four different approaches were pursued for the establishment of the physical map of this area which allowed the assembly of an uninterrupted YAC contig spanning an estimated 10-12 megabases, with an average STS resolution of 140 kb or for the 25 polymorphic microsatellites on this map, of 400 kb. Twelve genes and 25 genetic markers were positioned in this contig, which is constituted of a minimum of 10 clones. PMID- 8004097 TI - An explanation for the constitutive exon 9 cassette splicing of the DMD gene. AB - Approximately half of the transcripts of the DMD gene isolated from peripheral blood lymphocytes and detected by RT-PCR do not contain exon 9. This 'exon skipping' can be observed to a variable extent in all tissues not specifically expressing the gene product 'dystrophin'. The shorter transcript is rare in muscle, heart and brain. Similar results were found in mice. Since the 3' end of exon 9 reflects the consensus sequence of a 3' splice site, it is suggested that exon 9 due to this sequence element is 'recognized' as an intron and removed from an RNA intermediate. This model is supported by a mathematical comparison of real and putative splice sites within the gene. PMID- 8004098 TI - Localization of the gene for dominant cystoid macular dystrophy on chromosome 7p. AB - In a family with autosomal dominant cystoid macular dystrophy (DCMD) linkage was detected with the dinucleotide marker D7S435 on the short arm of chromosome 7. With markers flanking D7S435, the DCMD locus could be assigned to the interval D7S493-D7S526 at 7p15-p21, which spans approximately 20 cM. Three-point linkage yielded a maximal lod score of 9.46 and location score of 43.5 and suggested that DCMD is 5,5 cM proximal to D7S493. Recently, a retinitis pigmentosa (RP7) locus has been mapped in roughly the same area of chromosome 7. Genetic data of both studies described below, allow a region of overlap between the location of the DCMD and the RP7 gene between D7S435 and D7S526. Both genes being one and the same will further substantiate the close relationship between macular degeneration and retinitis pigmentosa. PMID- 8004099 TI - Additional mutations of type X collagen confirm COL10A1 as the Schmid metaphyseal chondrodysplasia locus. AB - Type X collagen is a short chain collagen expressed in hypertrophic chondrocytes during bone growth. A 13bp deletion has been shown to segregate with Schmid metaphyseal chondrodysplasia, an autosomal dominant disorder of the osseous skeleton, in a large Mormon kindred. To increase our understanding of the role type X collagen plays in development we have used SSCP analysis to identify three additional mutations in patients with Schmid metaphyseal chondrodysplasia. Two are frameshift mutations (1856delC and 1992delCT) and one is a missense mutation (C591R). Of interest, the apparently unaffected mother of the patient with the missense mutation is a somatic mosaic for the mutant allele. All three mutations are in the carboxy-terminal non-collagenous domain suggesting that the effect of these mutations is to impair the mutant polypeptide's ability to participate in chain association and trimer formation. PMID- 8004100 TI - Imprinting analysis of three genes in the Prader-Willi/Angelman region: SNRPN, E6 associated protein, and PAR-2 (D15S225E). AB - In order to identify genes in the Prader-Willi/Angelman syndrome critical region, radiolabeled cDNA probes from poly(A)+ RNA from mouse tissues were used to identify potential exon-containing genomic DNA fragments in cosmid or phage clones from appropriate yeast artificial chromosomes, and these fragments were subsequently used to screen human cDNA libraries. A mouse brain cDNA probe was effective in detecting control genes of various abundance including small nuclear ribonucleoprotein polypeptide N (SNRPN), hypoxanthine-guanine phosphoribosyl transferase, glyceraldehyde-3-phosphate dehydrogenase, and beta-actin. Two genes mapping within the Angelman syndrome critical region were isolated. One gene was found to encode the E6-associated protein (E6-AP; gene symbol HPVE6A), a protein which interacts with the E6 protein of human papilloma virus. The other gene is previously uncharacterized and is designated PAR-2 (D15S225E) for Prader-Willi and Angelman region-gene 2. Imprinting analysis using reverse transcription polymerase chain reaction of RNA from fibroblasts and lymphoblasts of deletion Prader-Willi and Angelman patients demonstrated imprinting of SNRPN with exclusive expression from the paternal allele, but E6-AP and PAR-2 were not imprinted in these cultured human cells. The ability to analyze for imprinting and expression of SNRPN and other genes in this region in cultured human cells will be a valuable tool for analyzing the molecular basis of the Prader-Willi and Angelman syndromes, although imprinting may differ between cultured cells and tissues.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8004101 TI - Aberrant splicing of the COL4A5 gene in patients with Alport syndrome. AB - A variety of mutations have been identified in the X-linked type IV collagen alpha 5 chain (COL4A5) gene in patients with Alport syndrome. A substantial number of these mutations were predicted to have an effect on RNA splicing. For 4 such mutations in our group of patients the effect of the DNA mutation on the COL4A5 mRNA structure and stability was analysed. An alteration of the invariant splice acceptor site of intron 41 resulted in a shift of the actual splicing to either a cryptic splice site within exon 42 or the normal splice site in the next intron. A single base substitution of the final nucleotide of exon 48 resulted in the removal of the entire exon. Two frameshift mutations, a 10 basepair duplication in exon 49 and a single base deletion in exon 41, were incorporated in the mRNA as such and resulted in a stretch of missense codons terminated by a premature stop codon. Exon skipping was occasionally observed in these samples, but not reproducibly in every experiment. In healthy controls exon skipping was never detected. Analysis of female carriers revealed that in only one case was the stability of the mutated mRNA reduced in comparison with the normal transcript. The extent to which the non-collagenous domain was predicted to be deleted correlated with the severeness of the disease. PMID- 8004102 TI - Gene for autosomal dominant congenital stationary night blindness maps to the same region as the gene for the beta-subunit of the rod photoreceptor cGMP phosphodiesterase (PDEB) in chromosome 4p16.3. AB - We studied a large multigeneration Danish family with autosomal dominant congenital stationary night blindness. Both electrophysiological and psychophysical findings in affected family members were identical to those reported in patients from the 'Nougaret family'. The disease locus in the Danish family has now been mapped by demonstrating close linkage without recombination (Q = 0.00 at Zmax = 14.4) to the locus for alpha-L-iduronidase assigned to chromosome 4p16.3. Interestingly the gene for the beta-subunit of the rod photoreceptor cGMP-specific phosphodiesterase maps to the very same chromosomal region. PMID- 8004104 TI - A point mutation responsible for human erythrocyte AMP deaminase deficiency. AB - A point mutation of C to T on the human erythrocyte AMP deaminase gene (AMPD-3) has been identified by molecular analysis of the genetic materials from the enzyme deficient individuals. Four separate DNA fragments covering the entire coding region of AMPD-3 cDNA were amplified using polymerase chain reaction (PCR) technique and sequenced directly. The same point mutation was detected in both of the two B-lymphoblast cell lines derived from the complete deficiency of human erythrocyte AMP deaminase: a single nucleotide substitution of C to T resulted in an amino acid change of Arg to Cys at the codon 573. The analysis of genomic DNA demonstrated that two individuals with complete deficiency were homozygous for the detected mutation, and two individuals with partial deficiency were diagnosed as heterozygous. This mis-sense mutation reads to a catalytically inactive enzyme. PMID- 8004103 TI - Congenital adrenal hyperplasia caused by a novel homozygous frameshift mutation 273 delta AA in type II 3 beta-hydroxysteroid dehydrogenase gene (HSD3B2) in three male patients of Afghan/Pakistani origin. AB - Classical 3 beta-hydroxysteroid dehydrogenase (3 beta-HSD) deficiency is an autosomal recessive form of congenital adrenal hyperplasia caused by mutations in the type II 3 beta-HSD (HSD3B2) gene. The sequence of the type II 3 beta-HSD gene was determined by direct sequencing of asymmetric PCR products in three male infants suffering from a severe salt-losing form of 3 beta-HSD deficiency and belonging to three families originating from Afghanistan and Pakistan. The three patients were homozygous for the frameshift mutation 273 delta AA resulting from deletion of two adenosines at codon 273, thus leading to a premature termination codon at position 279. This mutation was detected in the heterozygous state in all the relatives studied. The observation that all three patients share the same haplotype for HSD3B1A, HSD3B1C, HSD3B2A, and the microsatellite marker D1S252 indicates that a founder effect is responsible for the severe form of 3 beta-HSD deficiency found in these three families. PMID- 8004105 TI - The E subunit of vacuolar H(+)-ATPase localizes close to the centromere on human chromosome 22. AB - As part of a general effort to identify new genes mapping to disease-associated regions of human chromosome 22, we have isolated heterogeneous nuclear RNA from somatic cell hybrids selected for their chromosome 22 content. Inter-Alu PCR amplification yielded a series of human DNA fragments which all detected evolutionarily-conserved sequences. The centromere-most gene fragment candidate, XEN61, was shown to lie centromeric to the chromosome 22 breakpoint in the X/22 33-11TG somatic cell hybrid. This region, which is still devoid of characterized genes, overlaps with the critical region for the cat eye syndrome (CES), a developmental disorder associated with chromosomal duplication within 22pter q11.2. Gene dosage analysis performed on DNA from six CES patients consistently revealed the presence of four copies of XEN61. A fetal brain cDNA clone, 61EW, was identified with XEN61 and entirely sequenced. The deduced protein is the E subunit of vacuolar H(+)-ATPase. This 31 KDa component of a proton pump is essential in eukaryotic cells as it both controls acidification of the vacuolar system and provides it with its main protonmotive force. RT-PCR experiments using oligonucleotides designed from the 61EW cDNA sequence indicated that the corresponding messenger is widely transcribed. PMID- 8004106 TI - Assignment of sterol carrier protein X/sterol carrier protein 2 to 1p32 and its exclusion as the causative gene for infantile neuronal ceroid lipofuscinosis. AB - In the positional cloning of a disease gene with an unknown protein defect a spectrum of molecular biological methods is applied after linkage has been established. It is reasonable to analyze in detail any relevant candidate gene mapping to the particular chromosomal region. We report here the refined chromosomal assignment of SCPx/SCP2, a gene coding for the protein that is believed to have an important role in lipid metabolism by transporting many kinds of lipid molecules between organelles. This gene represents an excellent candidate gene for infantile neuronal ceroid lipofuscinosis, earlier assigned to 1p32 by us, since lipid metabolism in the patient's brain appears to be significantly disturbed. Expression and structural analyses by Northern, Southern and Western blotting as well as SSCP and direct sequencing did not detect any differences between the cDNAs of patients and controls. Consequently, it is unlikely that a mutation in SCPx/SCP2 is the underlying cause of this severe neurodegenerative disease of childhood. PMID- 8004107 TI - Somatic NF2 gene mutations in familial and non-familial vestibular schwannoma. AB - Vestibular schwannoma occurs both as a sporadic tumour and in the dominantly inherited familial cancer syndrome neurofibromatosis type 2 (NF2). The gene for NF2 has recently been isolated on chromosome 22, and the demonstration of inactivating germline mutations in NF2 patients and NF2 associated tumours suggests that it act as a tumour suppressor. We have investigated 85 sporadic and 2 NF2 associated vestibular schwannomas, and one vagal schwannoma for chromosome 22 allele loss and NF2 gene mutations. A further 7 vestibular schwannomas were investigated for NF2 mutations only. Chromosome 22 allele loss was detected in 34 of 87 vestibular schwannomas and in the vagal nerve schwannoma. Six exons of the NF2 gene were investigated by SSCP analysis in all 95 tumours. Somatic NF2 gene mutations were detected in 13 non-familial vestibular schwannomas and in one of the NF2 vestibular schwannomas. Seven non-familial tumours with an NF2 gene mutation also displayed a chromosome 22 allele loss. Thirteen of the mutations were predicted to produce truncation of the NF2 protein. These results suggest that somatic mutations of the NF2 tumour suppressor gene are a critical step in the pathogenesis of both familial and non-familial vestibular schwannoma and that the mechanism of tumourigenesis complies with a 'two-hit' mutation model. PMID- 8004108 TI - Identification of a sixth locus for autosomal dominant retinitis pigmentosa on chromosome 19. AB - We report the mapping of a sixth locus for autosomal dominant retinitis pigmentosa (adRP) to 19q13.4. After a total genome linkage search using over 300 markers in a single large pedigree, marker loci on the long arm of chromosome 19 showed significant linkage with the disease locus. Since the mapping information for the marker loci used in this study was derived from two different genome maps, we established genetic distances between relevant marker loci so that linkage information could be combined from both maps. A conventional three point analysis between the adRP phenotype and markers D19S180 and D19S214 gave a maximum lod score of 4.87. Combining data from these and other markers, we used the recently described multiple two point programme FASTMAP to simulate a multipoint analysis of the full data set. This gave a lod score of 5.34 in the interval between markers D19S180 and D19S214. Recently this laboratory has also reported the linkage of another form of retinal degeneration known as cone-rod dystrophy (CRD) to a genetically different set of markers from 19q. Linkage data presented here clearly supports the existence of two separate retinal genes in this part of the genome. PMID- 8004109 TI - Point mutations of the connexin32 (GJB1) gene in X-linked dominant Charcot-Marie Tooth neuropathy. AB - Ten families with X-linked dominant CMT neuropathy (CMTX1) were screened for point mutations of the connexin32 (Cx32, GJB1) gene. Two families showed missense mutations, respectively an A-->G transition at amino acid 102 (glutamate to glycine) and a C-->T transition at amino acid 142 (arginine to tryptophan). Three families showed nonsense mutations, respectively a C-->T transition at amino acid 22 (arginine to stop) a G-->T transversion at amino acid 186 (glutamate to stop), and a T-->A transversion at amino acid 217 (cysteine to stop). Five CMTX1 neuropathy families showed no evidence of point mutations of the connexin32 coding sequence. These findings suggest that the CMTX1 neuropathy genotype is heterogeneous or the result of promoter mutations, 3'-untranslated region mutations or exon/intron splice site mutations. Four of the reported mutations created or destroyed restriction enzyme sites: a HaeIII restriction enzyme site was destroyed by the mutation at amino acid position 22, a HpaII site was eliminated at amino acid position 142, a Bfal restriction site was created by the mutation at amino acid 186 and a Ddel restriction site was created by the mutation at amino acid 217. These changes allowed us to test family members for the mutations and observe the segregation of the disease with the mutations. PMID- 8004110 TI - Identification of a new missense point mutation in exon 4 of the Cu/Zn superoxide dismutase (SOD-1) gene in a family with amyotrophic lateral sclerosis. PMID- 8004111 TI - Retinal pattern dystrophy associated with a 4 bp insertion at codon 140 in the RDS-peripherin gene. PMID- 8004112 TI - Two novel mutations and a neutral polymorphism in EGF-like domains of the fibrillin gene (FBN1): SSCP screening of exons 15-21 in Marfan syndrome patients. PMID- 8004113 TI - Steroid 11 beta-hydroxylase deficiency caused by a five base pair duplication in the CYP11B1 gene. PMID- 8004114 TI - Chromosome 13 and chromosome 2 (CA)n polymorphisms. PMID- 8004115 TI - Three dinucleotide markers on chromosome 21. PMID- 8004116 TI - Dinucleotide repeat polymorphism at D15S221. PMID- 8004117 TI - Two dinucleotide repeats tightly linked to D12S91. PMID- 8004118 TI - Tetranucleotide repeat polymorphism at the D8S474 locus. PMID- 8004120 TI - New alleles in F7 VNTR. PMID- 8004119 TI - Dinucleotide repeat polymorphisms in the HSD3B2 gene. PMID- 8004121 TI - Dinucleotide repeat polymorphism at D7S813. PMID- 8004122 TI - Tetranucleotide repeat polymorphism (D8S582) for human EST00680 (D8S340E). PMID- 8004123 TI - Transcribed dinucleotide repeat polymorphism in the IGF2 gene. PMID- 8004125 TI - Dinucleotide repeat polymorphism at the DXS1283E locus. PMID- 8004124 TI - Dinucleotide repeat polymorphism at D9S328E (EST hbc220). PMID- 8004126 TI - VNTR at the DXYS14 locus. PMID- 8004127 TI - Dinucleotide repeat polymorphism at the D18S336 locus. PMID- 8004128 TI - Jun and Fos regulation of NAD(P)H: quinone oxidoreductase gene expression. AB - NAD(P)H:Quinone oxidoreductase1 (NQO1) is a flavoprotein which promotes obligatory two-electron reduction of quinones, preventing their participation in redox cycling, oxidative stress and neoplasia. High levels of NQO1 have been observed in several kinds of tumours including that of the liver, lung, colon and breast. Transcription of the NQO1 gene is increased in response to bifunctional [e.g. beta-naphthoflavone (beta-NF), 2,3,7,8,-tetrachlordibenzo-p-dioxin (dioxin)] and monofunctional [phenolic antioxidants/chemoprotectors e.g. 2(3)tert butyl-4-hydroxy-anisole (BHA)] inducers. High basal expression of the NQO1 gene and its induction by beta-NF and BHA are mediated by 31 bp of the antioxidant response element (ARE) containing more than one copy of the AP1/AP1-like binding sites, Jun and Fos and other(s) as yet unknown regulatory proteins. The arrangement of AP1/AP1-like elements within a short region of DNA may be important for beta-NF and BHA response. The high basal expression of the NQO1 gene in several types of tumour tissues may be due to a high expression and/or modification of regulatory proteins that result from tumour formation. Signal transduction from beta-NF and BHA for increased expression of the NQO1 gene involve metabolism of beta-NF and generation of 'redox signals'. The sequence of events after generation of 'redox signals' leading to the modification/activation of regulatory proteins that bind to ARE and increase expression of the NQO1 gene are less clear. The possibilities include involvement of protein(s) which receive signals from beta-NF and BHA and modulate the Jun and Fos proteins for increased binding to the ARE element or increased activities of the transcriptional activation domains of the regulatory proteins. The modifications in the regulatory proteins may be reduction of a cysteine residue in the DNA binding domain and/or phosphorylation of the DNA binding/transcriptional activation domains. Further studies are required to identify the intermediary components in the signal transduction pathway to completely understand the mechanism of induction of the NQO1 gene expression in response to beta-NF and BHA. Dioxin induction of the NQO1 gene expression is mediated by XRE, an element best characterized in the case of the CYP1A1 gene.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8004129 TI - Selective expression of cytochrome P450 CYP3A mRNAs in embryonic and adult human liver. AB - The human CYP3A P450 family, composed of at least four highly homologous genes, is expressed prominently in the liver. To investigate the expression of CYP3A family members individually, we prepared oligonucleotides specific for each CYP3A mRNA and used Northern blot analysis and/or polymerase chain reaction to examine RNA from adult and fetal liver for variation in expression of the CYP3A forms during development. We found that CYP3A4 (P450NF) mRNA, was only detectable by Northern blot postnatally, was highly variable (10-fold) among the adult samples, and, unlike its rat counterparts (CYP3A1/2), was not influenced by gender. In contrast, CYP3A7 (HFLa) mRNA, a form previously thought to be confined to fetal liver, was found in all tested samples of fetal liver as well as in seven of 13 adult livers (54%). CYP3A5 (HLp2), an mRNA also found in all the fetal samples, was detected in three of these 13 adults (23%) and two of these three co expressed CYP3A7 mRNA. CYP3A5 and CYP3A7 are expressed at similar levels in fetal liver from either gender. Moreover, CYP3A7 expression in fetal liver appears less variable (< 2.5-fold) than CYP3A4 in adults. We conclude, that contrary to prevailing views, expression of CYP3A7 in the liver is not restricted to the fetus but rather represents a second CYP3A form selectively expressed in adults. PMID- 8004130 TI - Stereoselective disposition of hexobarbital and its metabolites: relationship to the S-mephenytoin polymorphism in Caucasian and Chinese subjects. AB - In vitro studies with human liver preparations suggest that the metabolism of hexobarbital involves CYP2CMP--the determinant of the S-mephenytoin 4' hydroxylation polymorphism, but no in vivo evidence of interphenotypic differences exist. The pharmacokinetics and urinary excretion of hexobarbital and its metabolites were, therefore, investigated following oral administration of a differentially labelled pseudoracemate that allowed determination of the fate of the individual enantiomers. Studies were undertaken in 10 Caucasian and nine Chinese healthy subjects known to be either extensive (EM) or poor (PM), metabolizers of mephenytoin. No inter-racial differences were observed in any of the measured parameters within a given phenotype. However, pronounced stereoselectivity in disposition was noted in EMs with R-(-)-hexobarbital's oral clearance being five- to six-fold greater than that for the S-(+)-enantiomer. By contrast, the S-(+)-isomer was eliminated twice as fast as R-(-) hexobarbital in PMs and, in addition, the oral clearances of both enantiomers were significantly reduced compared with their values in EMs. Formation of 3'-hydroxy- and 3' ketohexobarbital and 1,5-dimethylbarbituric acid were the major identified routes of metabolism for each enantiomer in both phenotypes. Furthermore, these pathways were found to co-segregate with the mephenytoin polymorphism and in EMs they were primarily responsible for the observed stereoselectivity in disposition. These findings, therefore, confirm the stereoselectivity in hexobarbital's disposition in humans and identify the major pathways of metabolism involved. Additionally, the results indicate that CYP2CMP is a major determinant of the in vivo metabolism of both of hexobarbital's enantiomers but especially that of the R-(-) enantiomer. PMID- 8004131 TI - Impaired (S)-warfarin metabolism catalysed by the R144C allelic variant of CYP2C9. PMID- 8004132 TI - Cytochrome P450-dependent metabolism of acetaminophen in four human transgenic lymphoblastoid cell lines. PMID- 8004133 TI - Morbidity and mortality of dialysis. AB - The National Institutes of Health Consensus Development Conference on Morbidity and Mortality of Dialysis brought together experts in general medicine, nephrology, pediatrics, biostatistics, and nutrition as well as the public to address the following questions: (1) How does early medical intervention in predialysis patients influence morbidity and mortality? (2) What is the relationship between delivered dialysis dose and morbidity/mortality? (3) Can co morbid conditions be altered by non-dialytic interventions to improve morbidity/mortality in dialysis patients? (4) How can dialysis-related complications be reduced? and (5) What are the future directions for research in dialysis? Following 1 1/2 days of presentations by experts and discussion by the audience, a consensus panel weighted the evidence and prepared their consensus statement. Among their findings, the consensus panel concluded that (1) patients in the predialysis phase, including children, should be referred to a renal team in an effort to reduce the morbidity and mortality incurred both during the predialysis period and when receiving subsequent dialysis therapy; (2) the social and psychological welfare and the quality of life of the dialysis patient are favorably influenced by the early predialytic and continued involvement of a multidisciplinary renal team; (3) attempts should be made to avoid a catastrophic onset of dialysis by instituting predialytic intervention and the appropriate initiation of dialysis access; (4) quantitative methods now available to objectively evaluate the relationship between delivered dose of dialysis and patient morbidity and mortality suggest that the dose of hemodialysis and peritoneal dialysis has been suboptimal for many patients in the United States; (5) factors contributing to underdialysis of some patients include problems with vascular and peritoneal access, nonadherence to dialysis prescription, and underprescription of the dialysis dose; (6) cardiovascular mortality accounts for approximately 50 percent of deaths in dialysis patients, and relative risk factors such as hypertension, smoking, and chronic anemia should be treated as soon as possible after diagnosis of chronic renal failure; (7) early detection and treatment of malnutrition contribute to improved survival of patients on dialysis; and (8) until prospective, randomized, controlled trials have been completed, a delivered hemodialysis dose at least equal to a measured fractional urea clearance of Kdrt/V of 1.2 (single pool) and a delivered peritoneal dialysis dose at least equal to a measured Kprt/V of 1.7 (weekly) are recommended. PMID- 8004134 TI - Relieving the pressure. PMID- 8004135 TI - A student's struggle. PMID- 8004137 TI - Private hospitals face closure. PMID- 8004136 TI - Women's work. PMID- 8004138 TI - A tale of two hospitals. PMID- 8004139 TI - Protecting patients. PMID- 8004140 TI - Restoring health to Cambodia. PMID- 8004141 TI - The representation of medical reasoning models in resolution-based theorem provers. AB - First-order predicate logic essentially is a language to express knowledge concerning objects and relationships between objects in a domain. Many medical problems can be cast naturally in such terms. In this paper the suitability of logic as a knowledge-representation formalism for building medical expert systems is investigated. In particular, we investigate the logical representation of three typical reasoning models in medicine: diagnostic, anatomical and causal reasoning. It turns out that each of these models has its own characteristic logical structure. Furthermore, the pragmatics of using theorem-proving techniques in consulting such logic-based medical expert systems is discussed. In particular, attention is paid to the use of a meta-level architecture to improve the applicability of theorem-proving techniques in building expert systems. PMID- 8004142 TI - Symbolic decision support in medical care. AB - Symbolic decision procedures offer a flexible alternative to classical quantitative procedures for decision making, particularly when precise parameters (such as probabilities) are hard to estimate. One such procedure, based on a logic of argumentation, is described. Specifications of inference methods for such functions as proposing and refining decision options, deducing and inheriting arguments for and against options, and selecting among alternatives are presented. These exploit declarative models for patient data, domain and task knowledge. A simple method for translating the specifications into executable Prolog is described. A practical and efficient toolset for using the procedure in a wide range of clinical environments is being developed within the DILEMMA project of the European Commission's Advanced Informatics in Medicine research programme. PMID- 8004143 TI - Logic-based integrity constraints and the design of dental prostheses. AB - This paper describes the ongoing development of a design assistant, RaPiD, for use in prosthetic dentistry. RaPiD integrates computed-aided design, knowledge based systems and databases, employing a logic-based representation as the unifying medium. The user's manipulation of icons representing the developing design is interpreted as a set of transactions on a logic database of design components. The rules of design expertise are represented as constraints in first order predicate logic and design alterations are subject to the checking of the constraints. When design rules are contravened as the result of some proposed alteration, a suitable critique is presented to the user. RaPiD is being developed for use in both dental education and practice. PMID- 8004144 TI - A constraint logic programming framework for constructing DNA restriction maps. AB - Restriction mapping is an important computational problem in molecular biology, particularly in genetic engineering and DNA sequencing. It is different in that it is not only a purely computational problem but involves an interaction between experimental data collection procedures and the mapping algorithms. Consequently, the problem is loosely defined and in practice requires a flexible and versatile algorithm. We describe a framework for solving many restriction mapping problems in the constraint logic programming language CLP (R) which takes advantage of the declarative and powerful features of constraint logic programming. A CLP (R) algorithm is developed for solving a simple restriction mapping problem. The algorithm is the extended to handle more complex variations of restriction mapping such as fragments with errors, circular maps, multiple enzymes and partial digests. The mapping variants are integrated within the same framework and differ in the constraints required to define the kind of map consistency. Various search heuristics and control strategies to improve the search process are also incorporated as constraints. PMID- 8004145 TI - A causal and temporal reasoning model and its use in drug therapy applications. AB - Superficial knowledge about drug effects and interactions may provide clinicians with only a limited support for the elaboration of therapy plans. Deeper knowledge of the mechanisms through which drugs produce their effects, together with their temporal constraints, should be modelled to predict the effects and interactions of their joint administration. The present paper describes a method for modelling such deep medical knowledge, together with its causal and temporal reasoning capabilities, and compares it with classical approaches to temporal and causal reasoning, namely in the context of drug treatment applications. This method extends a previous causal functional model by allowing the representation of quantitative knowledge, the explicit representation of time intervals, and a temporal reasoning technique, Simulation by Interval Constraining. The method is illustrated by a number of examples of basic drug metabolic mechanisms; and its future use in the development of decision support systems for complex drug therapy applications is discussed. PMID- 8004146 TI - Integrating consultation and semi-automatic knowledge acquisition in a prototype based architecture: experiences with dysmorphic syndromes. AB - The paper describes an application of cognitive theories of Tversky and Rosch to prototype similarity of dysmorphic syndromes cases. The knowledge-based system supports diagnostic consultation and research in dysmorphic syndromes. It has been used routinely for many years. The knowledge base is semi-automatically generated from known cases of an outpatient clinic. Some results of the evaluation process of the system's achievements are shown. General conclusions based on the experience with this successful system are discussed. PMID- 8004147 TI - Polygenic trait analysis by neural network learning. AB - AI techniques have been applied to the domain of DNA sequence analysis in predicting or identifying certain specialized regions, in recognizing genes, and in understanding the evolutionary relationships between sequences. This paper focuses on a kind of genetic pattern recognition, namely, the problem of identifying the gene combinations (patterns) causally related to a given trait determined by multiple genes (a so-called polygenic trait). A novel approach is presented which combines neural-network and knowledge-based techniques. The neural network is trained to predict the trait and then the knowledge embedded in the network is decoded into symbolic patterns. This hybrid approach is evaluated in the domain of identifying genes of insulin dependent diabetes mellitus. The consistency between the results with this approach and those reported in genetic literature supports the viability of this approach. PMID- 8004148 TI - A support for decision-making: cost-sensitive learning system. AB - This paper investigates a machine learning (ML) algorithm for supporting a decision-making system that is able to handle diagnostic problems. The input data are expressed by solved cases of patients' diagnoses, and the output is formed by a set of decision rules which may be directly exploited for a decision support. We have chosen the methodology of covering ML algorithms, namely the CN2 algorithm, as a starting point, and designed and implemented a certain extension of CN2 that comprises: advanced discretizing numerical attributes and incorporating attribute cost to economize the classification. PMID- 8004149 TI - Fundamentals of clinical methodology: 1. Differential indication. AB - Progress in the theory and practice of artificial intelligence in medicine requires awareness of basic issues in medical problem solving. To stimulate discussion and research on this subject, in a series of articles some logical, methodological and meta-theoretical problems of clinical practice will be studied. The present paper reconstructs clinical decision-making as a computable process of action planning. PMID- 8004150 TI - Apotransferrin can elevate intracellular free calcium ion and stimulate mitogenesis in human leukemic HL60 cells. AB - In order to resolve the question whether or not transferrin could have a growth promoting effect on cells independent of its action in iron transport, we investigated the effect of the iron-free form of transferrin, apotransferrin on cell activation and proliferation in the human leukemic HL60 cell line. Within a minute of its addition to HL60 cells, apotransferrin caused a rise in intracellular free calcium concentration ([Ca2+]i) in a dose-dependent manner and the higher the apotransferrin, the quicker it was to attain the calcium peak, showing the physiological characteristics of an agonist-induced [Ca2+]i elevation. The source of calcium appears to be extracellular since this signal could be abolished by nickel or when the reaction was carried out in calcium-free medium. Addition of apotransferrin in the serum-free medium could markedly promote DNA synthesis whereas addition of iron citrate could not. However, apotransferrin could not sustain cell proliferation and hypertrophism without other growth or nutritional factors. Antitransferrin receptor antibody inhibited the growth of HL60 cells cultured in serum-free medium supplemented with transferrin and insulin in a dose-dependent manner, whereas addition of ferric citrate could not reverse cell growth. Generation of the calcium signal probably reflects the initiation of the cell activation processes which could culminate into mitogenesis. Hence, our results suggest that apotransferrin, not iron, is bioactive in HL60 cells. PMID- 8004152 TI - Myenteric and submucosal plexuses of the congenital aganglionosis rat (spotting lethal) as revealed by scanning electron microscopy. AB - A rat with a congenital aganglionosis develops a mega-small intestine and megacolon. This rat mutant has been used as an animal model for Hirschsprung's disease. The myenteric and submucosal plexuses of the rats were exposed by the trypsin-HCl digestion method and examined by scanning electron microscopy. In the control rats the myenteric and submucosal plexuses were present throughout the gut. However, in the mutant rats the myenteric plexus of duodenum was different from those of control rats; the mesh of plexuses varied both in size and shape. There were no myenteric or submucosal plexuses in the distal ileum or colon. PMID- 8004151 TI - Enhanced generation of O2- by human neutrophils via a complement iC3b/Mac-1 interaction. AB - There is evidence for a tumor necrosis factor alpha (TNF alpha)-initiated and CD11b/CD18-dependent burst of superoxide anion (O2-) and hydrogen peroxide production by human polymorphonuclear leukocytes which are adherent to surfaces bearing a variety of proteins. In the current studies neutrophils were stimulated with opsonized (by fresh human serum) zymosan particles in the presence of cytochalasin B, to prevent internalization of particles and to simulate the interaction of neutrophils with protein-bearing surfaces. Under these conditions, the cells demonstrated 2.9-fold greater production of O2- when compared to nonopsonized zymosan particles. Heat inactivation or cobra venom factor treatment of human serum prior to opsonization resulted in 98% and 66% reductions, respectively, in O2- responses. C3 and factor B were required for this response, since sera deficient in either component caused 56 and 68% reductions, respectively, in O2- production. Sera deficient in Clq, C2, C4, C5, C6, C7 or C9 showed no defect in their ability to enhance O2- responses to zymosan particles. Monoclonal antibody to iC3b, but not monoclonal antibodies to C3c or C3d, caused a 29% reduction (p < 0.01) in O2- generation. Antibodies to CD18 (R15.7) or CD11b (CL44 and 60.1) reduced the incremental production of O2- by 76, 71 and 77%, respectively. Two antibodies directed against CD11a as well as the isotype matched control (MOPC 21) were without effects. These data suggest that, in this model of neutrophil activation, the pathway for O2- generation is a Mac-1 (but not LFA-1)-dependent pathway and also requires iC3b. These findings may be relevant to complement-mediated, neutrophil-dependent vascular injury in vivo. PMID- 8004153 TI - Differential effects of short photoperiod on 2-[125I]iodomelatonin binding in the testis and brain of quail. AB - The affinities and densities of 2-[125I]iodomelatonin binding sites in the brains and gonads of male Japanese quail following short photoperiod treatment were studied. At 6 weeks old, control quail were placed under a 14 hour light/10 hour dark photo-stimulatory cycle and experimental quail were housed under a 7 hour light/17 hour dark photo-inhibitory lighting regime. Eighteen weeks after photic manipulation, the birds were killed at mid-light. The photo-inhibited quail had very small testes. Brains and testes of control and experimental quail were collected for receptor binding studies. The maximum number of binding sites (Bmax) of 2-[125I]iodomelatonin determined by saturation studies and the number of 2-[125I]iodomelatonin binding sites determined by a one-point binding assay in the testes of short-day quail were significantly lower (p < 0.05) than those of the testes in reproductively active birds kept under long photoperiod. There was no significant difference (p > 0.05) between the testicular Kd (equilibrium dissociation constant) values of these two groups. As for the Kd and Bmax of 2 [125I]iodomelatonin binding sites in the whole brain, there were no significant differences (p > 0.05) between the two groups. The higher level of testicular 2 [125I]iodomelatonin binding sites in photostimulated birds may be related to an up-regulation of melatonin receptors by the suppressed pineal melatonin secretion under long photoperiod. The lower testicular 2-[125I]iodomelatonin binding sites under short photoperiod may be the result of down-regulation of melatonin receptors by the stimulated melatonin pattern in the photo-inhibited birds.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8004154 TI - Characterization of cell types within a chorionic gonadotropin-secreting, mechanically dissociated human placental cell population in perifusion. AB - A cell perifusion system was established to examine human placental endocrine regulation by locally synthesized peptides. First-trimester and term trophoblast cells were mechanically dissociated. Cells were plated on microcarrier beads and cultured for 7-14 days. Cells on beads were loaded in chambers, perifused with culture media and effluent was assayed for chorionic gonadotropin (hCG). Mechanical dissociation of placental tissue produced cell preparations with 85 95% viability. Staining with Masson trichrome, cytokeratin and beta-hCG antibodies suggested that greater than 50% of the cells were trophoblast. Perifused trophoblast cells secreted hCG in a continuous non-pulsatile fashion, independent of exogenous hormonal stimuli. hCG secretion from first-trimester trophoblast cells remained stable in static culture for 14 days. GnRH perifusion (10(-8) M) for 15-120 s transiently increased hCG secretion from first-trimester trophoblast cells. Longer GnRH exposure stimulated greater hCG secretion. Each of 3 consecutive pulses of 8-bromo-cyclic adenosine-3',5'-monophosphate (cAMP, 10( 9) M) administered at 2-hour intervals stimulated transient hCG secretion from first-trimester and term placental cells. cAMP stimulated hCG secretion more potently from first-trimester than from term placental cells. PMID- 8004155 TI - Changes in circulating and tissue angiotensin II during acute and chronic stress. AB - Changes of angiotensin II and cAMP in plasma, brain tissue, adrenal gland and cardiovascular tissue during the acute and chronic stress were studied in rats. The acute stress group was subjected to compulsive cold water swimming for 20 min, while the chronic stress group was exposed to an ambient temperature of 4-8 degrees C for 5 days. The results indicated that plasma angiotensin II levels were significantly increased in both stress groups, reaching up to 900% and 134% of the control in the acute and chronic groups, respectively. Angiotensin II contents in the anterior hypothalamus, medulla oblongata, myocardium, vasculature and adrenals were also elevated in both groups. With the exception of the adrenals, the contents of tissue angiotensin II in the chronic stress animals were significantly higher than those of the acute stress animals. In contrast, cAMP levels in plasma and tissue (hypothalamus and adrenals) and corticosterone levels in plasma in the acute stress group were all higher than those in the chronic stress animals, although the levels of the latter group were also increased compared with the control group. These results suggest that circulating and tissue angiotensin II may play an important role in the acute and chronic stress responses and that angiotensin II should be classified as a stress hormone. PMID- 8004156 TI - Computer analysis of sequence data. PMID- 8004157 TI - Staden: using patterns to analyze nucleic acid sequences. PMID- 8004158 TI - Staden: analyzing sequences to find genes. PMID- 8004159 TI - Staden: statistical and structural analysis of protein sequences. PMID- 8004160 TI - Staden: searching for motifs in protein sequences. PMID- 8004161 TI - Staden: using patterns to analyze protein sequences. PMID- 8004162 TI - Staden: comparing sequences. PMID- 8004163 TI - Staden Plus. PMID- 8004164 TI - DNA Strider. A Macintosh program for handling protein and nucleic acid sequences. PMID- 8004165 TI - MacVector: an integrated sequence analysis program for the Macintosh. PMID- 8004166 TI - MacVector: aligning sequences. PMID- 8004167 TI - MacVector: sequence comparisons using a matrix method. PMID- 8004168 TI - MacVector: restriction enzyme analysis. PMID- 8004169 TI - MacVector: protein analysis. PMID- 8004170 TI - Profile analysis. PMID- 8004171 TI - Staden: sequence input, editing, and sequence library use. PMID- 8004172 TI - Classification and function prediction of proteins using diagnostic amino acid patterns. PMID- 8004173 TI - CLUSTAL V: multiple alignment of DNA and protein sequences. PMID- 8004174 TI - Progressive multiple alignment of protein sequences and the construction of phylogenetic trees. PMID- 8004175 TI - The AMPS package for multiple protein sequence alignment. PMID- 8004176 TI - TreeAlign. PMID- 8004177 TI - Using the FASTA program to search protein and DNA sequence databases. PMID- 8004178 TI - Staden: managing sequence projects. PMID- 8004179 TI - Converting between sequence formats. PMID- 8004180 TI - Obtaining software via INTERNET. PMID- 8004181 TI - Staden: statistical and structural analysis of nucleotide sequences. PMID- 8004182 TI - Staden: searching for restriction sites. PMID- 8004184 TI - Staden: introduction. PMID- 8004183 TI - Staden: translating and listing nucleic acid sequences. PMID- 8004185 TI - Staden: searching for motifs in nucleic acid sequences. PMID- 8004186 TI - DNase I footprinting. PMID- 8004187 TI - Footprinting with exonuclease III. PMID- 8004188 TI - Diffusible singlet oxygen as a probe of DNA deformation. PMID- 8004189 TI - Ethylation interference. PMID- 8004190 TI - Uranyl photofootprinting of DNA-protein complexes. PMID- 8004191 TI - Nitration of tyrosine residues in protein-nucleic acid complexes. PMID- 8004192 TI - Limited proteolysis of protein-nucleic acid complexes. PMID- 8004193 TI - Cloning and expression of DNA binding domains using PCR. PMID- 8004194 TI - Overexpression and purification of eukaryotic transcription factors as glutathione-S-transferase fusions in E. coli. PMID- 8004195 TI - Site-directed mutagenesis by the cassette method. PMID- 8004196 TI - Hydroxyl radical footprinting. PMID- 8004197 TI - Site-directed and site-saturation mutagenesis using oligonucleotide primers. PMID- 8004198 TI - UV laser-induced protein-DNA crosslinking. PMID- 8004199 TI - Ultraviolet crosslinking of DNA-protein complexes via 8-azidoadenine. PMID- 8004200 TI - Filter-binding assays. PMID- 8004201 TI - The gel shift assay for the analysis of DNA-protein interactions. PMID- 8004202 TI - Improved plasmid vectors for the analysis of protein-induced DNA bending. PMID- 8004203 TI - Determination of sequence preferences of DNA binding proteins using pooled solid phase sequencing of low degeneracy oligonucleotide mixtures. PMID- 8004204 TI - Analysis of DNA-protein interactions by intrinsic fluorescence. PMID- 8004205 TI - A competition assay for DNA binding using the fluorescent probe ANS. PMID- 8004206 TI - Hydroxyl radical interference. PMID- 8004207 TI - Circular dichroism for the analysis of protein-DNA interactions. PMID- 8004208 TI - Electron microscopy of protein-nucleic acid complexes. Uniform spreading and determination of helix handedness. PMID- 8004209 TI - Reconstitution of protein-DNA complexes for crystallization. PMID- 8004210 TI - Assay of restriction endonucleases using oligonucleotides. PMID- 8004211 TI - Assays for restriction endonucleases using plasmid substrates. PMID- 8004212 TI - Assays for transcription factor activity. PMID- 8004213 TI - An assay for in vitro recombination between duplex DNA molecules. PMID- 8004214 TI - 1,10-Phenanthroline-copper ion nuclease footprinting of DNA-protein complexes in situ following mobility-shift electrophoresis assays. PMID- 8004215 TI - Identification of protein-DNA contacts with dimethyl sulfate. Methylation protection and methylation interference. PMID- 8004216 TI - Diethyl pyrocarbonate as a probe of protein-DNA interactions. PMID- 8004217 TI - Osmium tetroxide modification and the study of DNA-protein interactions. PMID- 8004218 TI - NSAIDs in the treatment of osteoarthritis. Friends or foes? PMID- 8004219 TI - Lyme disease--1993. PMID- 8004220 TI - Doing no harm: rethinking an old standard in a new era. PMID- 8004221 TI - A measurement of torque values obtained with hand-held drivers in a simulated clinical setting. AB - PURPOSE: This study measures the amount of torque that can be applied to the heads of implant screws via hand-held drivers and wrenches in a simulated clinical setting. MATERIALS AND METHODS: Sixty second-year dental students applied their maximum controlled torque to the head of a hex instrument attached to a Tonichi torque gauge mounted in a mannequin. The torque values obtained were recorded, and a mean torque value was calculated RESULTS; The mean torque value obtained in this study was 11.55 N.cm. CONCLUSIONS: Small-diameter, 10 N.cm gold screws can be adequately tightened with manufacturer-supplied instrumentation. Larger screws requiring more than 10 N.cm of torque cannot be tightened manually using currently available hand-held screwdrivers and hand wrenches. PMID- 8004222 TI - A comparison of the tensile strength of four prosthodontic adhesives. AB - PURPOSE: This study compared the in vitro tensile bond strength of four prosthodontic adhesives to sandblasted base-metal alloy. MATERIALS AND METHODS: Alloy cylinders were bonded end-to-end with the various adhesives, thermocycled, stored for 28 days, and subjected to a tensile load. RESULTS: Mean tensile bond strengths obtained were: Panvia = 42.3 MPa, Metabond = 31.1 MPa, All-Bond = 28.06 MPa, and F21 = 18.5 MPa. Statistical analysis showed significant differences (P < .05) in mean bond strengths between the adhesive systems. CONCLUSION: Under the conditions of this study, the Panavia system showed the strongest mean tensile bond strengths. PMID- 8004223 TI - Verifying the reliability of interchanging casts between Hanau Modular articulators. AB - PURPOSE: The purpose of this study was to test the Hanau Modular Articulator system with programmed fossae to determine its interchangeability. MATERIALS AND METHODS: Eight Hanau Modular Articulators were tested using the same measuring system as previously developed in a similar investigation on a different instrument. RESULTS: It was determined that the Hanau Modular System with programmed fossae did possess accuracy when a measuring device was transferred between the eight articulators tested. CONCLUSIONS: Laboratory procedures for multiple restorations can be accomplished with accuracy when master casts and mountings are transferred between Hanau Modular Articulators. PMID- 8004224 TI - Clinical applications of a polyphosphazene-based resilient denture liner. AB - The use of resilient denture liners provides an invaluable modality in removable prosthodontic treatment. Treatment of atrophic mandibles, preoperative and postoperative soft tissue management, and retention of removable prosthesis are a few applications of these materials. This article describes the clinical application of a polyphosphazene-based liner (Novus, Hygenic Corp, Dayton, OH) as a denture liner and retentive material in conventional and implant overdenture rehabilitation. PMID- 8004225 TI - First-stage fixed provisional restorations for implant prosthodontics. AB - Combination metal-and-acrylic-resin fixed provisional prostheses can be used in implant dentistry as an alternative to a removable provisional prosthesis. They may be fabricated in the laboratory and inserted on the day of fixture placement to ensure that the patients may return to their normal lifestyles with minimal discomfort or interruption in function and esthetics. These interim restorations may be used in free-standing as well as hybrid types of implant supported prostheses. The materials used and techniques of fabrication are described. PMID- 8004226 TI - Liquid-liquid extraction of a recombinant protein, cytochrome b5, with aqueous two-phase systems of polyethylene glycol and potassium phosphate salts. AB - The partitioning of cytochrome b5 in aqueous two-phase systems of polyethylene glycol (PEG) and potassium phosphate salts was investigated. Cytochrome b5 partitioning is enhanced with decreasing polymer molecular mass and with increasing tieline length and pH. The effect of cytochrome b5 mutation, by substitution of the glutamic acid at positions 56 and 92 of the polypeptide chain by a lysine, on protein partitioning was also studied. Partitioning of cytochrome b5 mutants shows the same dependence on tieline length and pH, following the order cytochrome b5 > mutant 56 > mutant 92. PMID- 8004227 TI - Polyethylene glycol-potassium phosphate aqueous two-phase systems. Insertion of short peptide units into a protein and its effects on partitioning. AB - Two different tetrapeptides, AlaTrpTrpPro and AlaIleIlePro, were inserted near the C-terminus of the protein ZZT0. The Trp-rich peptide unit strongly increased both the partitioning of ZZT0 into the polyethylene glycol (PEG)-rich phase in a PEG-potassium phosphate aqueous two-phase system and its retention on PEG and propyl hydrophobic interaction chromatographic columns with potassium phosphate as eluent. Both the partitioning and the retention increased with increasing number of Trp-rich peptide units inserted into ZZT0. Insertion of Ile-rich tetrapeptide units affected the partitioning and retention to a much lesser extent. Partition data also indicated a folding of inserted Trp tetrapeptides units, probably to minimize their water contact. PMID- 8004228 TI - Separation and purification of recombinant proteins from Escherichia coli with aqueous two-phase systems. AB - The partition of the protein thaumatin in the presence of Escherichia coli contaminant proteins has been studied. Extraction of thaumatin was followed by back-extraction of the product into a new phosphate phase and also back extraction combined with recycle of the top polyethylene glycol (PEG) phase. When partitioned in the absence or presence of insoluble cell debris (whole cell homogenate) little effect on the partitioning of thaumatin or the soluble E. coli protein was observed. A back extraction step that allowed for dilution of the NaCl was successful in extracting thaumatin back into a heavy phosphate phase. The PEG top phase was recycled to the first extraction stage. The stability ratio (tie-line length) had an effect on the average partition coefficient (Kapp) of E. coli soluble proteins in PEG-phosphate systems but in PEG sulphate systems Kapp was independent of this ratio. An increase in NaCl resulted in an increase in Kapp but this was always below 1. A mathematical model that describes the continuous steady-state operation of extraction and back extraction has been developed; it is based on steady state mass balances of the main components and phase equilibrium data and was successfully used to simulate the extraction and back extraction processes. PMID- 8004229 TI - Biochemical characterization of human erythrocytes fractionated by counter current distribution in aqueous polymer two-phase systems. AB - The fractionation of normal human erythrocytes by counter-current distribution (CCD) in charge-sensitive dextran-polyethylene glycol two-phase systems was confirmed and extended to red blood cells from heterozygous beta-thalassaemic patients. The differences between the distribution profiles of normal (homogeneous) and abnormal (heterogeneous) red blood cells reflect their different surface-charge properties. As suggested by the decline of membrane sialic acid released after neuraminidase treatment and the specific activities of two age-dependent enzymes (membrane acetylcholinesterase and intracellular pyruvate kinase) in the distribution profiles (from the left- to the right-hand side fractions), the fractionation seems to be according to red blood cell age. A constancy of the 2,3-bisphosphoglycerate level was observed in ageing red blood cells. PMID- 8004231 TI - Determination of dapsone in serum and saliva using reversed-phase high performance liquid chromatography with ultraviolet or electrochemical detection. AB - A simple, extractionless method for the determination of dapsone in serum and saliva is described. Reversed-phase high-performance liquid chromatography is used with UV detection at 295 nm or electrochemical detection at 0.7 V. Diazoxide in buffer is the internal standard for UV detection and practolol for electrochemical detection. Sample preparation is minimal with protein precipitation of serum samples whilst saliva samples are simply diluted with addition of an internal standard. Low-level serum and saliva samples are front cut on-line with a 3 cm laboratory-made precolumn in the loop position on a standard Valco injection valve. Isocratic separation is achieved on a 250 mm x 4.6 mm I.D. stainless-steel Spherisorb S5 ODS-1 column. The mobile phase for high levels of dapsone is acetonitrile-elution buffer (12:88, v/v) at 2 ml/min and a column temperature of 40 degrees C for both serum and saliva separations. For the low-level assays using electrochemical detection and solid-phase clean-up, the mobile phase is acetonitrile-methanol-elution buffer (9:4:87, v/v/v). The UV and electrochemical detection limits are 25 ng/ml and 200 pg/ml, respectively, in both serum and saliva. This simple method is applicable to the routine monitoring of dapsone levels in serum from leprotic patients and electrochemical detection gives a simple, reliable method for the monitoring of trough values in subjects on anti-malarial prophylaxis. PMID- 8004230 TI - Simple and sensitive determination of 2,3-butanediol in biological samples by gas chromatography with electron-capture detection. AB - 2,3-Butanediol was quantitatively oxidized into diacetyl by reaction with MnO4- at 20 degrees C for 30 min under neutral conditions. The reaction of diacetyl with 4,5-dichloro-1,2-diaminobenzene afforded 6,7-dichloro-2,3-dimethyl quinoxaline (DCDMQ), which was extracted with n-hexane and determined by gas chromatography with electron-capture detection. As an internal standard 1,2 cyclohexanediol was used. The detection limit of DCDMQ (or 2,3-butanediol) was 10 fmol/microliter in the extract, and the determination limit of DCDMQ (or 2,3 butanediol) was at least from 50 fmol/microliter to 20 pmol/microliter in the extract. Recoveries from normal rat urine and rat liver homogenate were 97.8 +/- 3.4% and 98.4 +/- 2.9%, respectively. The method is very simple and sensitive and is applicable to the determination of 2,3-butanediol in normal rat tissues. PMID- 8004232 TI - Sample clean-up and high-performance liquid chromatographic techniques for measurement of whole blood rapamycin concentrations. AB - Determination of rapamycin (RAPA), a potential adjunct to cyclosporin immunosuppressive therapy in solid organ transplantation, presents a challenge because of the agent's unusual chemical properties. RAPA is not readily extracted from biological matrices, is light-sensitive, and exists in numerous isomeric forms. Using liquid-liquid extraction techniques with tert.-butyl methyl ether followed by ethanol, one achieves 96% recovery of RAPA and 70% recovery of the internal standard, beta-estradiol-3-methyl ether, from human whole blood. Subsequent high-performance liquid chromatography (HPLC) utilizing two heated reversed-phase C18 columns in tandem and an 85% methanol-water mobile phase with ultraviolet detection at 276 nm provides measurement of RAPA from 1-ml samples of human whole blood. The chromatography requires less than 40 min per sample. The assay exhibits < or = 10% standard error of the mean and < or = 12% coefficient of variation over the concentration range 2-100 ng/ml. The method has been tested using pharmacokinetic profiles from renal transplant recipients receiving bolus intravenous RAPA infusions. PMID- 8004233 TI - Stereoselective determination of verapamil and norverapamil by capillary electrophoresis. AB - An analytical method has been developed to determine simultaneously the verapamil and norverapamil enantiomers in human plasma using capillary electrophoresis. Among the cyclodextrins tested as chiral selector, only trimethyl-beta cyclodextrin was suitable to resolve the four enantiomers. The analysis was achieved in less than 10 min. Selectivity, linearity, precision and accuracy were evaluated before the chiral method was successfully implemented for routine use to simultaneously determine the four enantiomers in several thousands of human plasma samples. The robustness of the capillary electrophoretic method and its suitability were demonstrated by the coefficients of variation which were lower than 11%, even at the limit of quantification (2.5 ng/ml), for the analysis of more than one hundred quality control samples. PMID- 8004234 TI - Simple determination of retinol, alpha-tocopherol and carotenoids (lutein, all trans-lycopene, alpha- and beta-carotenes) in human plasma by isocratic liquid chromatography. AB - Retinol, alpha-tocopherol, lutein, all-trans-lycopene, and alpha- and beta carotenes can be simultaneously determined in human plasma by reversed-phase liquid chromatography with a programmable and variable UV wavelength detector. Plasma (200 microliters) is deproteinized with 200 microliters of ethanol containing retinyl acetate, as internal standard, then extracted with 1.0 ml of n hexane-2,6-di-tert.-butyl-p-cresol (BHT). The organic layer is removed and evaporated and the residue is dissolved in 100 microliters of a mixture of acetonitrile-tetrahydrofuran-methanol (68:22:7, v/v/v). Aliquots (15 microliters) are injected onto a 250 x 4.6 mm I.D. column of Nucleosil 100-5 C18 with a pre column of Lichrosorb RP-18, 7 microns, 15 x 3.2 mm I.D. A mobile phase of acetonitrile-tetrahydrofuran-methanol (68:22:7, v/v/v), adjusted to 100 (v/v) with 1% ammonium acetate, at a flow-rate of 1.5 ml/min is used. Usual run time is 15 min. Retinol and retinyl acetate are monitored at 325 nm, tocopherol at 290 nm, lycopene at 470 nm, lutein and alpha- and beta-carotenes at 450 nm. The intra batch coefficients of variation (C.V.) were 2.5, 2.2, 2.4, 5.8, 5.1 and 4.7% for retinol, alpha-tocopherol, lutein, trans-lycopene, alpha- and beta-carotenes, respectively. The inter-batch C.V.s of experiments performed on 30 different days over 12 weeks were 5.7, 3.9, 4.5, 10.9, 11.3 and 10.5%, respectively. PMID- 8004235 TI - Measurement of ascorbic acid in human plasma and urine by high-performance liquid chromatography. Results in healthy subjects and patients with idiopathic calcium urolithiasis. AB - A simple, reliable high-performance liquid chromatographic method was developed to measure ascorbic acid (ASC), with ultraviolet detection (250 nm), in human plasma and urine. Immediately following blood withdrawal, the heparinized plasma samples were deproteinized with 10% m-phosphoric acid, while the freshly voided urine samples were diluted with m-phosphoric acid. ASC was separated on a reversed-phase column by elution with 0.1 M KH2PO4 adjusted to pH 2.35. In urine, after reduction of dehydroascorbic acid to ASC, total ASC was measured using the same mobile phase. The method was sensitive down to 0.1 and 0.4 mg ASC per litre of urine and plasma, respectively. In patients with idiopathic calcium urolithiasis, both plasma and urinary ASC were within the range observed in age matched controls. PMID- 8004236 TI - High-performance liquid chromatographic assay for antiinflammatory agents diclofenac and flurbiprofen in ocular fluids. AB - An HPLC assay for diclofenac (DC) and flurbiprofen (FP) in a 100-microliters sample of aqueous humour is presented. After acetonitrile extraction, the residue is analyzed using a reversed-phase octyl column and ultraviolet detection. The method is simple and reproducible. Excellent selectivity and resolution are achieved using an acetic acid-acetonitrile-triethylamine mobile phase. The lower limit of detection, defined as the amount of drug required to produce a peak twice the threshold, was ca. 0.3 ng DC on column and ca. 0.4 ng on column FP. The utility of the method is demonstrated by determining drug levels in aqueous humour of normal rabbits and of patients undergoing cataract surgery. The assay should be applicable to other antiinflammatory agents. PMID- 8004237 TI - Sensitive high-performance liquid chromatographic assay for nifedipine in human plasma utilizing ultraviolet detection. AB - A rapid, simple, sensitive and selective reversed-phase high-performance liquid chromatographic (HPLC) technique is reported for the determination of nifedipine in human plasma. The procedure involves extraction of nifedipine from plasma under alkaline conditions (pH 12), separation via reversed-phase HPLC and ultraviolet detection (350 nm). The peak corresponding to nifedipine was free of interference from its photodegradation products or metabolites. The method was validated over the range 5-250 ng/ml nifedipine using weighted least-squares linear regression analysis. Accuracy and precision were within approximately 10% or less over the concentration range, except for the lowest concentration point which, nonetheless, was acceptable and approached 15%. The minimum quantifiable concentration of nifedipine was determined to be 5 ng/ml. The minimum detectable concentration was in the order of 1 ng/ml. Analysis of plasma samples collected from healthy volunteers demonstrate that this assay is applicable to clinical and pharmacokinetic studies. PMID- 8004238 TI - Enantiomeric separation of R- and S-ifosfamide and their determination in serum from clinical subjects. AB - A method to measure racemic, R- and S-ifosfamide concentrations from the serum of patients receiving ifosfamide chemotherapy has been developed. The racemic ifosfamide concentrations are quantified on a separate system and then the ratio of the enantiomers is determined using an achiral-chiral coupled system. Racemic ifosfamide is separated on the achiral system using a C1 spherisorb stationary phase and the eluent containing analyte is selectively transferred to the chiral system for separation of the two enantiomers by an alpha 1 glycoprotein column. On both systems the mobile phase is 1% acetonitrite in 0.015 M phosphate buffer (pH 4) at a flow-rate of 1 ml/min. The retention times of S- and R-ifosfamide were 11.6 and 13.0 mins, respectively, with a resolution factor of 1.53. Serum concentrations at least three to four half-lives post-infusion were detected by this method. In ten patients, following a mean +/- S.D. 1-h infusion of 3.9 +/- 0.32 g racemic ifosfamide, the mean +/- S.D. clearances of R- and S-ifosfamide were 0.061 +/- 0.013 and 0.072 +/- 0.014 1 h-1 kg-1. PMID- 8004239 TI - Determination of fenoverine in tissue samples by high-performance liquid chromatography. AB - Fenoverine is a spasmolytic, non-anticholinergic phenothiazine derivative that inhibits calcium channel currents. We describe a high-performance liquid chromatographic method for the determination of fenoverine in striated muscle, smooth muscle, myocardium, and liver tissue. Reversed-phase liquid chromatography was performed on a 5 microns Nucleosil C18 column with acetonitrile-0.015 M phosphate buffer (28:72, v/v) as a mobile phase and detection with ultraviolet at 214 nm. The limit of quantitation of fenoverine in tissue samples was 25 ng injected. This method is well suited for the determination of fenoverine in various organs in animal experiments. PMID- 8004240 TI - Determination of guanine and its nucleosides and nucleotides in human erythrocytes by high-performance liquid chromatography with postcolumn fluorescence derivatization using phenylglyoxal reagent. AB - A high-performance liquid chromatographic method with on-line postcolumn fluorescence derivatization is described for the simple and sensitive determination of guanine and its nucleosides and nucleotides in human erythrocytes. After deproteinization of the biospecimen, guanine and its nucleosides and nucleotides were separated on a reversed-phase column (TSKgel ODS 120T) by gradient elution with methanol in the aqueous mobile phase consisting of tetra-n-propylammonium phosphate (pH 6.0) and phosphate buffer (pH 6.0). The compounds were then automatically converted into fluorescent derivatives by reaction with phenylglyoxal. This derivatization was selective for guanine containing compounds. The present method permitted the reliable quantification of GDP and GTP in human erythrocytes. The detection limits (at a signal-to-noise ratio of 3) for guanine and its nucleosides and nucleotides were 3.2-10.0 pmol in a 20-microliters injection volume. The concentrations of GDP and GTP in human erythrocytes were 17.2 +/- 6.2 and 40.2 +/- 5.8 nmol/ml, respectively. PMID- 8004241 TI - Determination of acenocoumarol in human plasma by capillary gas chromatography with mass-selective detection. AB - A method for the determination of acenocoumarol in human plasma by capillary gas chromatography-mass-selective detection is described. After addition of a structurally related analogue as the internal standard, the compounds are extracted from plasma at acidic pH into toluene, back-extracted with a basic solution and re-extracted from hydrochloric acid solution with toluene, which is then evaporated to dryness. The compounds are converted into their methyl derivatives, which are determined by gas chromatography using a mass-selective detector at m/z 324 for acenocoumarol and m/z 338 for the internal standard. The reproducibility and accuracy of the method were found to be suitable over the acenocoumarol concentrations range 2.2-74 nmol/l. The method could be considered as selective for acenocoumarol in the presence of its major metabolites in plasma. PMID- 8004242 TI - Metabolites of 4-chlorotestosterone acetate in cattle urine as diagnostic markers for its illegal use. AB - Seven metabolites of 4-chlorotestosterone acetate were identified in urine of cattle that received a single injection of the drug. The steroids were isolated by means of a series of clean-up steps carried out before and after enzymatic hydrolysis. The obtained extract was fractionated by high-performance liquid chromatography and each fraction was examined both by high-performance thin-layer chromatography and by capillary gas chromatography-mass spectrometry of the m ethoxime-trimethylsilyl derivatives. The metabolites were tentatively identified by studying the mass spectra of selected peaks not found in blank samples. The structures of two metabolites, viz. 4-chloroandrost-4-ene-3,17-dione and 4 chloroandrost-4-ene-3 alpha,17 beta-diol were confirmed by chemical synthesis. The synthesized metabolites and 4-chloro-17 alpha-testosterone, a third metabolite which was identified tentatively, were located on the thin-layer chromatograms obtained. This study led to the conclusion that the illegal use of 4-chlorotestosterone acetate can be detected by identifying one or more of its metabolites in urine. PMID- 8004243 TI - Measurement of plasma probucol levels by high-performance liquid chromatography. AB - An improved assay for measuring plasma levels of probucol using reversed-phase high-performance liquid chromatography has been developed and used to measure probucol in cholesterol-fed rabbits. The sample was extracted with iso-octane, reconstituted in acetonitrile and was analysed using a Hypersil ODS column with a mobile phase consisting of acetonitrile-water (96:4, v/v). Detection was carried out using ultraviolet absorption at 241 nm. The lower detection limit for plasma probucol was 0.5 micrograms/ml. Inter-assay and intra-assay coefficients of variation were 1.8-4.8% and 1.6-3.3%, respectively. The method was applied to measurements of probucol in plasma from rabbits receiving a diet containing 1% probucol and 2% cholesterol for five weeks. Probucol levels at five weeks were significantly higher in the animals receiving concomitant cholesterol, and were close to the steady-state values predicted from the one week measurements. Also, the plasma probucol levels were positively correlated with total plasma cholesterol (r = 0.87, p < 0.001). The results indicate that bioavailability of probucol is dependent on the lipid content of the diet. PMID- 8004245 TI - Automated determination of midazolam in human plasma by high-performance liquid chromatography using column switching. AB - An automated gradient high-performance liquid chromatographic method using a column-switching technique was developed in order to determine and quantify midazolam (separated from the metabolite alpha-hydroximidazolam) in human plasma. After dilution with an internal standard (flurazepam) solution, containing 20% acetonitrile, 400 microliters of the plasma samples were injected onto a precolumn (17 x 4.6 mm I.D., C18 Corasil 37-53 microns) and retained. Proteins and polar plasma components were washed out using a 0.1 M sodium hydroxide solution, followed by an equilibration with a phosphate buffer of pH 8.0. After column-switching midazolam and flurazepam were eluted and transferred to the analytical column (RP-select B) in the backflush mode, separated by gradient elution and detected at 230 nm by ultraviolet detection. Precision of replicate analyses on the same day was 1.5% for midazolam and 0.7% for flurazepam. Recovery of midazolam was in the range 80-89% and the detection limit was 2 ng/ml plasma. PMID- 8004244 TI - High-performance liquid chromatographic enantioselective assay for the measurement of ketoprofen glucuronidation by liver microsomes. AB - A stereoselective high-performance liquid chromatographic (HPLC) method was developed to study the in vitro glucuronidation of ketoprofen enantiomers by liver microsomes. The HPLC system consisted of a Superspher 100 RP 18 end-capped column eluted with a mixture of acetonitrile and 10 mM tetrabutylammonium bromide in 1 mM potassium phosphate adjusted to pH 4.3 (30:70, v/v). Ultraviolet detection was performed at a wavelength of 254 nm. The capacity factors of S ketoprofen glucuronide, R-ketoprofen glucuronide and R,S-ketoprofen were 12.8, 14.5 and 18.1, respectively. Sample pretreatment consisted of protein precipitation in microsomal incubation suspensions and further purification on a Sep Pak C18 cartridge before injection onto the HPLC system. Quantitation was performed with standard glucuronides biosynthetized with immobilized microsomes and purified by semi-preparative HPLC. The linearity of the method between 1.25 and 25.0 micrograms ml-1 (coefficient of correlation greater than 0.999), the repeatability (coefficient of variation = 1.2%; n = 5), and recovery (within 85%) were tested. The limit of detection was 10 ng for each glucuronide injected. The in vitro glucuronidation of R- and S-ketoprofen was measured in liver microsomes from man and from various animal species (dog, rat, rabbit). For both enantiomers, dog presented the highest specific activity. In contrast, the lowest activity was found in rabbit. On the other hand, the formation ratio of the S- and R-glucuronides of ketoprofen was close to 1 in man, rat and rabbit, but was 4.5 in dog, thus indicating that the reaction was stereoselective in this species. PMID- 8004246 TI - Determination of alprazolam and its major metabolites in serum microsamples by high-performance liquid chromatography and its application to pharmacokinetics in rats. AB - A high-performance liquid chromatographic method using a single-solvent extraction step is described for quantitating alprazolam and its metabolites in rat serum microsamples (50 microliters). The separation used a 2-mm I.D. reversed phase Ultrasphere C18 column with a mobile phase of methanol-acetonitrile-sodium acetate buffer. By decreasing the methanol content in the mobile phase, triazolam and its metabolites can be extracted and separated using the same method. The detection limit was 5 ng/ml for all the compounds using an ultraviolet detector at 230 nm. The method showed the effect of aging on alprazolam pharmacokinetics following 0.8 mg/kg intravenous bolus alprazolam administration. PMID- 8004247 TI - Application of column-switching techniques to the determination of medium polarity drugs: determination of acetazolamide in urine. AB - A column-switching system for the determination of the medium polarity diuretic acetazolamide in urine, has been designed. An Hypersil ODS C18, 30 microns (20 x 2.1 mm I.D.) pre-column was used for the pre-concentration and separation of acetazolamide from the biological matrix. The most polar urinary compounds were removed by washing the pre-column with a phosphate buffer solution (pH 3), and the fraction of eluate containing the analyte was switched to a LiChrospher RP C18, 5 microns (125 x 4 mm I.D.) analytical column, where it was chromatographed using gradient elution with acetonitrile-water, and detected at 275 nm. The most apolar urinary compounds were directly discarded by means of a second switching valve. Under these conditions the recovery of drug was 96 +/- 5% in the 0.50 100.0 micrograms/ml concentration range. The limit of detection was 10 ng/ml, the total analysis time being less than 8 min. PMID- 8004248 TI - Volatile carbonyl levels in tissues of transgenic mice with nerve sheath tumors. AB - Volatile carbonyl compounds in homogenates prepared from various tissues of tumor bearing transgenic mice were determined. Formaldehyde and acetaldehyde were derivatized to thiazolidines. Malonaldehyde was derivatized to 1-methylpyrazole. The derivatives were quantified by gas chromatography with a highly sensitive and specific nitrogen-phosphorus detector. The limits of quantitation of formaldehyde and malonaldehyde were 2 micrograms/ml of homogenate and 27 ng/ml of homogenate, respectively. Levels of malonaldehyde in the erythrocytes and gastrocnemius of tumor-bearing transgenic mice were elevated as compared to the same tissue in control non-transgenic mice. Brain, liver, kidney, heart, and spleen tissues of the tumor-bearing mice exhibited decreased malonaldehyde levels. Similar results were obtained for formaldehyde and acetaldehyde. PMID- 8004250 TI - [Orientation of education of paramedical experts]. PMID- 8004249 TI - High-performance liquid chromatographic assay for the determination of the novel podophyllotoxin derivative dimethylaminoetoposide (NK611) in human plasma. AB - A simple, rapid and reproducible plasma assay for the determination of the novel epipodophyllotoxin derivative, dimethylaminoetoposide (NK611, I) and its N demethyl metabolite (II) is reported. The method involves solid-phase extraction using an isolute C18 cartridge and HPLC separation on a reduced-activity C18 column (8 cm long) with a mobile phase of acetonitrile-water-0.1 M phosphoric acid (23:76:1, v/v/v); peaks are detected at 205 nm. The intra- and inter-day precision and accuracy are within 5 and 4% for I and II, respectively. The sensitivity is 20 ng/ml for both I and II. The assay is applicable to clinical pharmacokinetic studies. In one cancer patient who received both an oral and an intravenous dose of 10 mg of I the bioavailability was 82% and the clearance 20.8 ml/min. PMID- 8004251 TI - [Specificities and interprofessional aspects in the education of paramedical specialists]. PMID- 8004252 TI - [Selection: a guarantee, some elitism]. PMID- 8004253 TI - [Unity of value, module, capitalization: for better adaptation to the job]. PMID- 8004254 TI - [The nurse and Europe]. PMID- 8004256 TI - [Psychiatric care and/or mental health care]. PMID- 8004255 TI - [Nursing diagnosis: a new translation]. PMID- 8004257 TI - [Mobility of the administrative nursing personnel. Exchange between a service facility and a nursing care education institute]. PMID- 8004258 TI - [Leadership for which public health facility in the year 2000?]. PMID- 8004259 TI - [Selection and prediction]. PMID- 8004260 TI - [Speaking out: for what?]. PMID- 8004261 TI - [Stress management in nursing. A new approach]. PMID- 8004262 TI - [The duration of night work: a heterogeneous reality. Those 35 hours]. PMID- 8004263 TI - [The pivot of the hospital system. The place of continued education]. PMID- 8004264 TI - [The law of 1978 and the decree of 1993. Concepts or words?]. PMID- 8004266 TI - [Simulator for intramuscular injections]. PMID- 8004265 TI - [A suffering body]. PMID- 8004267 TI - [Patients with dementia in nursing homes]. PMID- 8004269 TI - [Nursing management in the work with demented patients]. PMID- 8004268 TI - [Encounters in nursing]. PMID- 8004270 TI - [Limits of the ethics of love]. PMID- 8004271 TI - [A poll among coworkers makes for better working conditions]. PMID- 8004272 TI - [Healthy families for healthy nations]. PMID- 8004273 TI - [How does the family stay healthy?]. PMID- 8004274 TI - [Violence in marriage. What are the reasons?]. PMID- 8004275 TI - [Management of nursing in Europe. Aspects of education and continuing education]. PMID- 8004276 TI - [10 years of Agnes Karll Foundation for Nursing Research]. PMID- 8004277 TI - [Do nurses plan their careers?]. PMID- 8004278 TI - [Breathing and breathing experiences]. PMID- 8004279 TI - [Breathing work in everyday nursing]. PMID- 8004280 TI - [A visit in Arhus]. PMID- 8004281 TI - [Education in geriatric nursing]. PMID- 8004282 TI - [A beautiful calling--but is it to be recommended?]. PMID- 8004283 TI - [Planning of care in pediatric intensive care]. PMID- 8004284 TI - [Home care of German and foreign children. Legal an financial bases, reasons for care and activity spectrum]. PMID- 8004285 TI - ["Rooming-in for caregiving relatives. A possibility for improved care of patients with dementia in hospitals]. PMID- 8004286 TI - [Emotional and relational work. A chance for the definition of the nursing profession or a new dead end?]. PMID- 8004287 TI - [Work in hospital nursing in the new federal provinces]. PMID- 8004288 TI - [The rage about the lost penny]. PMID- 8004289 TI - Learning about air pollution and asthma. PMID- 8004290 TI - Indoor air pollution and asthma. Results from a panel study. AB - Although there is abundant clinical evidence of asthmatic responses to indoor aeroallergens, the symptomatic impacts of other common indoor air pollutants from gas stoves, fireplaces, and environmental tobacco smoke have been less well characterized. These combustion sources produce a complex mixture of pollutants, many of which are respiratory irritants. We report here results of an analysis of associations between indoor pollution and several outcomes of respiratory morbidity in a population of adult asthmatics residing in the Denver, Colorado, metropolitan area. A panel of 164 asthmatics recorded in a daily diary the occurrence of several respiratory symptoms, nocturnal asthma, medication use, and restrictions in activity, as well as the use of gas stoves, wood stoves, or fireplaces, and exposure to environmental tobacco smoke. Multiple logistic regression analysis suggests that the indoor sources of combustion have a statistically significant association with exacerbations of asthma. For example, after correcting for repeated measures and autocorrelation, the reported use of a gas stove was associated with moderate or worse shortness of breath (OR, 1.60; 95% CI, 1.11-2.32), moderate or worse cough (OR, 1.71; 95% CI, 0.97-3.01), nocturnal asthma (OR, 1.01; 95% CI, 0.91-1.13), and restrictions in activity (OR, 1.47; 95% CI, 1.0-2.16). Among this panel of relatively moderate to severe asthmatics, the respiratory irritants produced by several domestic combustion sources were associated with increased morbidity. PMID- 8004291 TI - Respiratory disorders and atopy in Danish refuse workers. AB - This survey describes respiratory and mucosal symptoms of garbage-handling and recycling workers in Denmark. The study includes 20 paper-sorting workers, eight compost workers, and 44 garbage-handling workers. As a control group, 119 workers from water purification plants of Copenhagen were chosen; workers in our study had a lower mean age and shorter mean employment time than did members of the control group. There was no significant difference in tobacco consumption between the groups. Garbage-handling workers were exposed to a significantly higher mean concentration (SD) of total dust than were water supply workers-0.74 (0.77) mg/m3 compared with 0.42 (0.25) mg/m3 (p < 0.05). Total count of microorganisms was significantly higher in garbage-handling and composting areas compared with paper sorting as well as water supply areas 0.46 (0.125) x 10(5), 0.54 (0.77) x 10(5), 4.7 (5.89) x 10(3), and 0.08 (0.04) x 10(3) cfu/m3, respectively (p < 0.05). This difference could not be explained as an effect of differential growth requirements. Significantly higher amounts of gram-negative bacteria were found in composting and garbage-handling plants than in water-supply plants. In garbage handling plants only, there were significantly higher amounts of endotoxins than in paper-sorting plants. Significantly higher prevalence of chest tightness (14%), flu-like symptoms (14%), itching eyes (27%), itching nose (14), and sore or itching throat (21%) were found among garbage-handling workers, compared with, respectively, 1, 1, 11 and 0% among water-supply workers. Furthermore, prevalence of nausea and vomiting or diarrhea rose from 2% and 7% among the water-supply workers to 19% and 27% among the garbage workers.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8004292 TI - Pre-exposure to ozone does not enhance or produce exercise-induced asthma. AB - We evaluated whether acute exposure to ozone (O3) enhances or produces exercise induced asthma (EIA) in asthmatic subjects who have or do not have EIA, according to standardized exercise challenge. Twenty-one otherwise healthy asthmatic subjects, 19 to 40 yr of age, with forced expiratory volume in one second (FEV1) greater than 70% of predicted and methacholine hyperresponsiveness, underwent three 1-h exposures on separate days to 0.10 ppm ozone in filtered air (FA), 0.25 ppm ozone in FA, and FA alone (randomized order, single-blinded, crossover design). Of these subjects, 12 underwent an additional exposure to 0.40 ppm ozone in FA. The subjects performed intermittent light exercise (with mean ventilation of 27 L/min) while in an environmentally controlled chamber (21 degrees C and 40% relative humidity). After each exposure, the subjects rested 1 h in clean air and performed serial postexposure spirometry. The subjects then underwent a standardized exercise challenge in clean air, followed by serial spirometry for 60 min. No significant changes in FEV1 or forced vital capacity (FVC) were found following 1-h exposures to 0, 0.10, and 0.25 ppm ozone (regardless of EIA status). The 12 subjects who underwent all four exposures showed a significant excess reduction in FEV1 (-0.35 +/- 0.37 L or -9.6%) after 1-h exposure to 0.40 ppm O3 (p = 0.017), regardless of EIA status. Postexposure FEV1 returned to baseline levels within 1 h. Postexposure changes in FVC showed similar magnitude and time course but were not statistically significant across exposure conditions or EIA status.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8004293 TI - A longitudinal study of the effects of parental smoking on pulmonary function in children 6-18 years. AB - The association between parental cigarette smoking and children's pulmonary function was investigated in 8,706 nonsmoking white children, followed annually by questionnaire and spirometry between 6 and 18 yr. Exposure to maternal and paternal smoking was each divided into three components: exposure in the first 5 yr of life, cumulative exposure between age 6 and the year prior to each visit; parental smoking status reported at each visit. Regression splines were used to assess the effects of parental smoking on the level and growth rate of pulmonary function adjusting for age, height, city of residence, and parental education. Models best predicting pulmonary function level included current maternal smoking and exposure to maternal smoking in the first 5 yr of life but did not include the other measures of parental smoking. After adjusting for early exposure, current maternal smoking for each pack/d was associated with a reduced level of FEV1 (-0.4%, 95% CI: -0.9, 0.1), FEV1/FVC (-0.6%, 95% CI: -0.9, -0.4), and FEF25 75% (-2.3%, 95% CI: -3.6, -1.0) in children 6 to 10 yr. These effects were slightly smaller in children 11 to 18 yr. Adjusting for current maternal smoking, those exposed to maternal smoking in the first 5 yr of life had higher FVC (+0.5%, 95% CI: -0.1, 1.2) and lower FEV1/FVC (-0.7%, 95% CI: -1.1, -0.4) and FEF25-75% (-2.8%, 95% CI: -4.4, -1.2) than those not exposed in children 6 to 10 yr.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8004294 TI - Dietary sodium intake, airway responsiveness, and cellular sodium transport. AB - Both epidemiologic and experimental evidence suggest that a high dietary sodium intake may increase airway responsiveness, but no adequate explanation exists of how changes in sodium intake might lead to increased responsiveness. This investigation was carried out to study dietary sodium intake and airway response to methacholine in relation to cellular sodium transport in 52 young men. Airway response to methacholine was associated with urinary sodium excretion when subjects were on normal sodium intake. Airway responsiveness in patients with mild asthma correlated with the furosemide-insensitive influx of sodium into peripheral leukocytes stimulated by autologous serum, but there was no relation between this influx and 24-h urinary sodium excretion. In a separate investigation, serum from subjects with increased airway responsiveness caused an increase in the sodium influx and sodium content of leukocytes from nonatopic subjects. The magnitude of the furosemide-insensitive, serum stimulated influx was related to the degree of airway responsiveness of the serum donor, as was the increase in intracellular sodium content. Neither was related to the 24-h urinary sodium excretion of the donor. Patients with airway hyperresponsiveness have an increased sodium influx into cells stimulated by a serum-borne factor. This is independent of the effect of added dietary sodium on airway responsiveness. PMID- 8004295 TI - Measurement of functional severity of asthma in children. AB - The usefulness of surveys for measuring the severity of asthma in school-age children depends on the availability of reliable and valid questionnaires. The aim of this study was to develop a measure of functional severity of asthma over the previous 12 mo, for use in population studies and in investigating treatment regimens. Of 10,198 children surveyed, 9,192 (90%) in school Years 2, 7, and 10 (mean ages 8, 13, and 16 yr) in Melbourne were screened for wheeze. The parents of the 1,267 children with wheeze were interviewed. Symptoms and restriction of activity due to asthma were analyzed using factor analysis and the partial credit version of the item response theory measurement model. The result was a continuous severity scale that was highly consistent with the data, and with goodness of fit statistics indicating the severity of 97% of children was well described by the scale. The scale correlated significantly with school absence due to wheeze (r = 0.35), functional impairment during the 2 wk before interview (Functional Status II-R [FSII-R], r = 0.30), visits to medical care for wheeze (r = 0.22), and amount of medication (r = 0.36). For descriptive purposes, a simple index with four bands of severity was developed from the continuous severity scale: low severity (47% of children with wheeze), moderate (30%), mild (18%), and high (5%). The scale and index facilitate standardized description of the impact of asthma on daily life on the basis of responses to six survey questions. PMID- 8004296 TI - Effective allergen avoidance at high altitude reduces allergen-induced bronchial hyperresponsiveness. AB - We studied the effects of reduced allergen exposure on bronchial hypereactivity (BHR) in two groups of asthmatic children allergic to house dust mites (HDM) living at high altitude for 9 continuous mo. In the first group the serum levels of total and HDM-specific IgE showed significant decreases after 3 mo (p < 0.001 and p < 0.02, respectively) and after 9 mo (p < 0.001). Three months after returning home the total IgE levels had increased significantly (p < 0.001). The mean percentage fall in peak expiratory flow after exercise testing improved after 3 and 9 mo (p < 0.05), but it had deteriorated after 3 mo at home (p < 0.01). The methacholine PD20-FEV1 increased after 3 mo (p = 0.001) and further after 9 mo (p < 0.001), with a decrease after the 3-mo period at sea level (p = 0.01). In the second cohort there was a significant increase in HDM PD20-FEV1 after 6 and 9 mo (p < 0.001), with a slight decrease of magnitude of the allergen induced late reaction. Histamine PD20-FEV1 significantly increased after 6 and 9 mo at high altitude, particularly in the challenges performed after the HDM bronchial provocation (p < 0.01). Our data demonstrate that allergen avoidance in asthmatic children not only decreases nonspecific BHR but also decreases allergen sensitivity, late allergen-induced bronchial reactions, and enhancement of BHR by allergen challenge. PMID- 8004297 TI - Postallergen inhaled budesonide reduces late asthmatic response and inhibits the associated increase of airway responsiveness to methacholine in asthmatics. AB - To determine whether inhaled budesonide given after allergen inhalation challenge inhibits the late asthmatic response (LAR) and/or the associated increase of airway responsiveness to methacholine, we performed a double-blind randomized cross-over study in 12 adult asthmatics (eight male, four female; mean age, 20.3 yr; range, 18 to 29 yr) sensitized to Dermatophagoides pteronyssinus (DP) previously shown to develop early and late asthmatic response to allergen challenge with DP. On different days each subject was randomized to receive budesonide 800 micrograms by Turbuhaler or placebo, given three times; (1) after allergen inhalation, after the onset of LAR, when FEV1 had fallen by > or = 15%; (2) 2 h later; (3) 4 h later. Airway responsiveness to methacholine was measured before allergen challenge at 8 to 10 h from allergen inhalation and 24 h after the allergen inhalation. Inhaled budesonide significantly reduced the LAR induced by allergen (maximal % fall in FEV1, delta FEV1%: -23 +/- 6% with budesonide versus -38 +/- 9% with placebo; p < 0.001) and inhibited the associated increase of airway responsiveness (geometric mean of PD20FEV1 methacholine: 0.047 mg after budesonide versus 0.033 mg after placebo at 8 to 10 h, p < 0.05; 0.119 mg after budesonide versus 0.062 mg after placebo at 24 h, p < 0.01). These results suggest that inhaled budesonide may not only prevent but also reduce the late asthmatic response induced by allergen and that it might also be considered in the treatment of exacerbation of asthma. PMID- 8004298 TI - Refractory period during provocation with eucapnic hyperventilation and methacholine. AB - Eucapnic voluntary hyperventilation (EVH) and methacholine inhalation challenge (MIC) both cause bronchoconstriction in asthmatics. A refractory period, or time when the response to bronchoprovocation in a series of challenges is diminished, has been found after hyperventilation or exercise but not after MIC. We investigated whether EVH or MIC blunted the response to the other test. Sixteen asthmatics were studied on 2 d, taking both tests each day. They were randomized to either EVH or MIC first on Day 1, then the opposite order on Day 2, 6 to 14 d apart. After EVH as a first test, the mean decline in FEV1 from baseline was 18.66 +/- 4.76% (mean +/- SEM), but when EVH followed MIC, the response to EVH was reduced by 30%, to a decline in FEV1 of only 13.02 +/- 3.75% (p = 0.0026). During MIC, the mean provocation dose to cause 20% decrease in FEV1 (PD20) given as the initial challenge was 54.77 +/- 21.60 breath units, compared with 46.94 +/ 19.55 breath units when MIC followed EVH (p = 0.54). However, the subset of patients most sensitive to methacholine (PD20 < 0.1 breath unit) had changes suggestive of a refractory period after EVH, with a mean increase in the PD20 from 0.06 +/- 0.01 to 3.35 +/- 1.43 (p = 0.069). Our data show that MIC attenuates the response to subsequent challenge with EVH. Conversely, EVH may only affect subsequent MIC in those most sensitive to methacholine. PMID- 8004300 TI - Endotoxin contamination causes neutrophilia following pulmonary allergen challenge. AB - Segmental bronchoprovocation (SBP) with allergen was used in an attempt to study eosinophils recruited to the airway 24 h after challenge. Unexpectedly, in the first four patients, neutrophils (rather than eosinophils) were recruited in the bronchoalveolar lavage (BAL) fluids, and we hypothesized that the allergen extracts were contaminated with endotoxin. The extracts used for challenge in the first four patients tested positive for bacterial endotoxin in a limulus amebocyte lysate assay. Rechallenge of one patient from the first group with a comparable dose of an endotoxin-free extract and SBP with endotoxin-free extract in five additional patients resulted in preferential recruitment of eosinophils rather than neutrophils. The number of neutrophils recovered from the challenged segments in the patients challenged with endotoxin-free extract was significantly less than that observed in the first four patients. Taken together, these observations suggest that neutrophil recruitment in the 24-h BAL fluids from the first four patients was probably due to endotoxin contamination of the allergen extract. We caution investigators that endotoxin contamination of allergen extract may alter the cellular inflammation during the late airway response following allergen challenge. PMID- 8004299 TI - Nebulized versus intravenous albuterol in hypercapnic acute asthma. A multicenter, double-blind, randomized study. AB - In a multicenter, randomized, double-blind study, we compared the effects of nebulized (5 mg x 2) and intravenous (0.5 mg) albuterol (salbutamol) over 1 h in 47 patients admitted to hospital with severe acute asthma defined as a peak expiratory flow (PEF) below 150 L/min and hypercapnia (Pa(CO2) > or = 40 mm Hg). Additional treatment included nasal oxygen and hydrocortisone succinate. The efficacy was assessed after 1 h. In the group treated by nebulization (NEB group, n = 22) 19 (86%) patients (95% confidence interval: 65 to 97%) had been treated successfully according to predefined criteria, versus 12 (48%) patients (95% confidence interval: 28 to 69%) in the intravenously treated group (i.v. group, n = 25), p = 0.006. The mean increase in PEF was greater in the NEB group than in the i.v. group (+107 +/- 94 L/min versus +42 +/- 66 L/min, p = 0.01) as well as the decrease in Pa(CO2) values (-10 +/- 5 mm Hg versus -2 +/- 12 mm Hg, p < 0.01). Beta agonist-induced hypokalemia was more pronounced in the i.v. group than in the NEB group. We conclude that, in hypercapnic acute asthma, the nebulized route has a greater efficacy and fewer side effects than the intravenous route. PMID- 8004301 TI - Functional results of single-lung transplantation for chronic obstructive lung disease. AB - The feasibility and immediate tolerance of single-lung transplantation were recently demonstrated in patients with severe obstructive lung disease. Since initial reports, hundreds of procedures have been performed worldwide in such patients, but views regarding the results are still controversial. Since few data concerning medium-term functional results are available, we report here our series of 20 patients with chronic obstructive pulmonary disease who received a single-lung transplant. A group of 16 patients who survived for 6 mo or more form the basis of this report. Current 1- and 2-yr actuarial survival are 75 and 70%, respectively, with 4 perioperative deaths and 2 deaths at 9 and 15 mo after transplantation. Before transplantation the patients were severely obstructive, with a FEV1 of 17 +/- 6% of predicted, a PaO2 of 51 +/- 10 mm Hg, a PaCO2 of 49 +/- 11 mm Hg, and a 6 min walk test of 99 +/- 84 m. A significant functional improvement was observed postoperatively, the patients' FEV1 at 3 mo reached 53 +/- 13%, PaO2 81 +/- 3 mm Hg, and PaCO2 39 +/- 3 mm Hg. The distance covered during 6 min was 587 +/- 147 m at 6 mo. Throughout postoperative follow-up, lung function remained stable in some patients but decreased in others after several mo, this decline related to the occurrence of bronchiolitis obliterans, except in two patients who had airway complications. Impairment in lung function led to retransplantation in four patients, with good clinical results in three patients, one patient dying postoperatively.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8004302 TI - Effect of inhaled nitric oxide on hemodynamics and VA/Q inequalities in patients with chronic obstructive pulmonary disease. AB - Nitric oxide (NO) has been reported to be an endothelium-derived relaxing factor, and hypoxic pulmonary vasoconstriction seems to be enhanced by inhibitors of endothelially dependent vascular relaxation. We examined the circulatory effects of inhalation of 15 ppm NO in air in 14 hypoxic patients suffering from chronic obstructive pulmonary disease (COPD). Of these patients 4 breathed 100% O2 before NO. The effects of NO inhalation on pulmonary gas exchange were also studied in 12 of these patients using the multiple inert gas elimination technique, 3 of whom breathed air, 100% O2, and 15 ppm NO in air in succession. Under baseline conditions, both mean +/- SD pulmonary artery pressure and pulmonary vascular resistance were increased (Ppa = 24.3 +/- 10.4 mm Hg and PVR = 3.3 +/- 1.1 mm Hg/L/min, respectively). Although the pulmonary circulatory effects were not immediate, with no detectable changes after 1 min NO inhalation, Ppa and PVR fell significantly (-19.1 +/- 10.5%, p < 0.02 and -29.3 +/- 15.1%, p < 0.02, respectively) after 10 min NO inhalation. Moreover, the extent of the NO-induced reduction in Ppa was found to depend on the level of baseline pulmonary arterial hypertension. No systemic circulatory effects were observed. The mean VA/Q ratio and the dispersion of ventilation and blood flow distributions were not altered by NO inhalation, although there was a significantly higher percentage of ventilation (7.3 +/- 7.3%, p < 0.05) in poorly and unperfused areas (VA/Q > 10).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8004303 TI - Involvement of thromboxane A2 in propranolol-induced bronchoconstriction after allergic bronchoconstriction in guinea pigs. AB - Although it is well recognized that beta-blockers can induce bronchoconstriction only in patients with asthma, mechanisms of the bronchoconstriction are not well known. We hypothesize that bronchoconstriction induced by beta-blockers may result from inflammatory mediators released by allergic reactions. In this study, we developed a guinea pig model for propranolol-induced bronchoconstriction (PIB) after antigen inhalation and investigated the effect of specific thromboxane (TXA2) receptor antagonists, S-1452 and ONO NT-126, on PIB in passively sensitized and artificially ventilated guinea pigs to determine whether TXA2 is involved in PIB. Propranolol caused bronchoconstriction with 10 mg/ml of propranolol was inhaled 20 min after antigen challenge. On the other hand, propranolol did not produce bronchoconstriction after antigen provocation in nonsensitized guinea pigs or after saline provocation in sensitized animals. Pretreatment of the animals with S-1452 in doses of 0.01 and 0.1 mg/kg and ONO NT 126 in doses of 1.0 and 10 micrograms/kg injected intravenously 15 min after antigen challenge as well as before antigen challenge reduced PIB in a dose dependent manner. Bronchoconstriction caused by methacholine did not induce PIB. These results suggest that TXA2 has an important role in the pathophysiology of the PIB that develops after the allergic bronchoconstriction. PMID- 8004304 TI - In vivo, in vitro correlation of acetylcholine airway responsiveness in sensitized guinea pigs. The role of modified epithelial functions. AB - Many attempts have failed to correlate in vivo airway responsiveness with in vitro airway smooth muscle functions. We have reexamined this relation by taking account of airway epithelial functions in guinea pigs sensitized with inhaled ovalbumin (OA). In vivo responses were assessed by the provocative concentration of acetylcholine (ACh) required to double the airway opening pressure (PC200) under mechanical ventilation. In vitro responses were measured in a perfused whole-tracheal preparation. The negative logarithm of the molar concentration of ACh required to produce a 10% reduction in diameter was calculated both for epithelial-side stimulation (PC10(in)) and for serosal-side stimulation (PC10(out)). OA-sensitized guinea pigs showed significantly smaller log PC200 than control animals (0.51 +/- 0.07 and 0.81 +/- 0.10, respectively, p < 0.01). In in vitro study, there were variable differences in PC10(in) and PC10(out) in each animal. The difference in sensitivity between epithelial- and serosal-side stimulation (PC10(in-out)) showed a significant correlation in PC10(in) (r = 0.82, n = 9, p < 0.01) but not to PC10(out) (r = 0.39, p > 0.1), indicating that the variation in PC10(in-out) resulted from the changes in PC10(in). For in vivo in vitro correlation, log PC200 correlated significantly with PC10(in) (r = 0.68, n = 9, p < 0.05) but not with PC10(out) (r = 0.18, p > 0.1). These results indicate that the sensitization by inhalation of OA produces increased airway responsiveness to ACh in vivo and that this airway responsiveness may be related, at least in part, to the altered airway epithelial functions. PMID- 8004305 TI - In vitro allergic bronchoconstriction in the brown Norway rat. AB - The ovalbumin (OA)-sensitized Brown Norway rat (BN) demonstrates early-response (ER) and late-response (LR) allergic bronchoconstriction. To determine whether these responses could be replicated in vitro, we studied lung explants from 8-wk old male BN rats (wt: 239 +/- 28 g), of which 19 were sensitized to OA (test) and 16 served as controls. Two weeks after sensitization, the animals' lungs were removed, filled with a 1% (wt/vol) agarose-containing solution at 37 degrees C, and cooled to 4 degrees C. Transverse slices (0.5 to 1.0 mm thick) were cut and cultured overnight. Airways were visualized with an inverted microscope and baseline images were obtained with a video camera. To study the ER, 40 airways from 15 test rats and 29 airways from 10 control rats were challenged with 2 micrograms OA and imaged each minute for 10 min. To study the LR, 40 airways from 12 test rats and 44 airways from 12 control rats were challenged with 2 micrograms OA and imaged each hour for 8 h. The maximal response (MR) for each airway was defined as the percent of airway closure. The ER and LR were both defined as an MR > or = mean + 2 SD of the controls. An ER occurred in 38 of 40 test and 2 of 29 control airways (mean MR: 42 +/- 24% versus 4 +/- 3%, p < 0.001), and was completely blocked by methysergide pretreatment in 13 airways.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8004307 TI - Inhibition of hypoxic pulmonary hypertension by heparins of differing in vitro antiproliferative potency. AB - Heparin inhibits smooth-muscle cell (SMC) growth in vitro and inhibits the development of hypoxic pulmonary hypertension and vascular remodeling in vivo. We wondered whether preparations of heparin with different antiproliferative potency in vitro would differ in their ability to inhibit the development of hypoxic pulmonary hypertension in vivo. Two such heparins, a weakly antiproliferative lot of Elkins-Sinn (E-S) (% inhibition of SMC growth at 10 micrograms/ml = 13 +/- 9% [mean +/- SEM, n = 24]) and a more active lot from Upjohn (UJ) (% inhibition = 71 +/- 12% [n = 12, p < 0.05 versus E-S]), were infused subcutaneously (300 U.S.P. units/day; E-S 300 versus UJ 300) via an osmotic pump into guinea pigs exposed to hypoxia (10% O2) for 10 d, after which pulmonary artery pressure (PAP; mm Hg) and cardiac index (CI; ml/min/kg) were measured in room air. Hypoxic controls (HC) received saline. PAP increased from 11 +/- 1 mm Hg in normoxic controls (NC) (n = 5) to 24 +/- 1 mm Hg in HC (n = 8, p < 0.05). The PAP was lower in the E-S 300 (21 +/- 1; n = 7, p < 0.05 versus HC and NC) and even lower in the UJ 300-treated group (18 +/- 0.5; n = 7, p < 0.05 versus HC and NC). Total pulmonary vascular resistance (TPR; mm Hg/ml/min/kg) increased significantly from 0.038 +/- 0.002 in NC to 0.076 +/- 0.003 (p < 0.05) in HC. There was no difference in TPR between the HC and the E-S 300-treated group.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8004306 TI - Pharmacologic characterization of a novel histamine receptor on human eosinophils. AB - There is increased recognition that lung mast cell mediators not only produce the symptoms of acute asthma, but also result in the recruitment and activation of additional proinflammatory cells, such as eosinophils. Histamine, one of the major mast cell mediators, is known to have numerous effects on eosinophil function. These effects of histamine are mediated by distinct receptors on the surface of eosinophils, only some of which have been characterized. Prior studies have suggested that eosinophils have non-H1, non-H2 histamine receptors which mediate the chemotactic effects of histamine. We observed previously that the histamine-induced increase in cytosolic calcium in human eosinophils could not be blocked by classic H1 or H2 antagonists, but could be inhibited by the H3 antagonist thioperamide. The purpose of this study was to further characterize the pharmacologic properties of this calcium-linked histamine receptor. Using Fura-2 loaded eosinophils to measure the concentration of cytosolic calcium, we examined the effect of additional histamine receptor antagonists and agonists. We found that the pKb for the H3 antagonists thioperamide, impromidine, and burimamide (8.1, 7.6, and 7.2, respectively), were similar to those reported for H3 receptors in the central nervous system, suggesting that the eosinophil histamine receptor was similar to H3 receptors. However, when the known H3 agonists were tested for activity ([R]-alpha-methylhistamine, N alpha methylhistamine), the potencies of these compounds were much less than the potency of histamine itself, indicating a significant difference between H3 receptors and this eosinophil histamine receptor.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8004308 TI - An investigation of the role of glutathione in increased epithelial permeability induced by cigarette smoke in vivo and in vitro. AB - Airspace epithelial permeability is known to increase in cigarette smokers. To study the role of the antioxidant reduced glutathione (GSH) in this phenomenon, we used an in vitro model of the epithelial permeability of a monolayer of human type II alveolar epithelial cells (A549 cell line). Both whole (WSC) and vapor (VSC) smoke condensates induced a recoverable, concentration-dependent increase in epithelial permeability to 125iodine-labeled bovine serum albumin (125IBSA), associated with a profound fall in intracellular GSH. Buthionine sulfoximine (BSO), a GSH synthesis inhibitor, decreased GSH levels in A549 epithelial cells, significantly increased A549 epithelial cell permeability, and enhanced both WSC and VSC-induced A549 epithelial cell permeability. Co-culturing epithelial cells and GSH (500 microM) reduced WSC-induced, but not VSC-induced A549 epithelial cell permeability. Increasing intracellular GSH also ameliorated the smoke induced increased epithelial permeability. Concentrations of cigarette smoke condensate of < 20% increased A549 epithelial cell permeability without associated cell detachment and lysis, which was also the case with BSO-induced increased epithelial permeability. WSC and VSC, instilled intratracheally, significantly increased rat lung epithelial permeability to 125IBSA, 6 h postinstillation, associated with a significant recruitment of neutrophils into the airspaces. This was associated with a small increase in GSH in the lung tissue of VSC-treated rats. However, both WSC and VSC markedly reduced GSH in bronchoalveolar lavage (BAL) fluid. Reduction in lung GSH to 95% but not to 68% of control values by BSO increased lung epithelial permeability in vivo. However, there was no additive effect on epithelial permeability of WSC and BSO.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8004309 TI - Neutrophil sequestration in lungs removed at surgery. The effect of microscopic emphysema. AB - Neutrophils within the lungs are considered to play an important role in the pathogenesis of pulmonary emphysema. We have studied the intravascular distribution of reinjected autologous 111In-labeled neutrophils in lung specimens resected 10 min after reinjection from 10 patients undergoing surgery for peripheral bronchogenic tumors. An excess of neutrophils relative to that expected for the 99mTc-labeled erythrocyte blood volume was confirmed in all specimens (range, 3- to 136-fold). In seven specimens which were completely examined, this excess displayed a skewed distribution, with a median neutrophil sequestration of 20-fold excess, and correlated with local blood volume (r = 0.51; p < 0.001). There was also a significant correlation between alveolar wall surface area per unit volume of lung (AWUV) and neutrophil excess, when randomly selected tissue blocks from each specimen were analyzed (r = 0.34, n = 51, p = 0.012). This same trend was demonstrated when whole specimen median values were considered (r = 0.64, n = 7, p = 0.07). Thus in areas of the lungs with lower AWUV values (increasing microscopic emphysema), fewer neutrophils were present. These studies add further support to the view that emphysema per se is not associated with an increased sequestration of pulmonary intravascular neutrophils. PMID- 8004310 TI - Effects of mechanical ventilation on diaphragmatic contractile properties in rats. AB - We measured in rats the effects of 48 h of mechanical ventilation on the weight, contractile properties, and enzymatic profile of the diaphragm, the soleus and the extensor digitorium longus (EDL) muscles. Eighteen animals were randomly divided into a mechanically ventilated (MV, n = 9) group or a control (C, n = 9) group. During the 48 h of mechanical ventilation, animals in the MV group were anesthetized with sodium thiopental and enterally fed with a gastric catheter. Group C animals were neither anesthetized nor mechanically ventilated during the 48-h experimental period, and they had access to food and water ad libitum. Muscular contractile properties were measured in vitro by analysis of force frequency curves and twitch characteristics. The weights of the three muscles were significantly reduced in the MV group compared with those in the C group. This was accompanied in the diaphragm by a reduction in the normalized force generated for all the frequencies of stimulation, except 20 Hz, whereas twitch characteristics were not modified. The forces generated by the soleus and EDL were not significantly reduced in the MV group compared with those in the C group. Diaphragm, soleus, and EDL citrate synthase and lactate dehydrogenase activities were not significantly different in the two groups. We conclude that mechanical ventilation for 48 h in rats produces a selective force reduction in the diaphragm. PMID- 8004311 TI - The effect of aminophylline on the force-length characteristics of the diaphragm. AB - The aim of our study was to evaluate the effect of aminophylline on the contractile function of the human diaphragm during varying muscle fiber length. Ten healthy subjects were studied during maximal sniff maneuvers and bilateral phrenic nerve twitch stimulations, with and without intravenous infusion of aminophylline in a randomized fashion. The transdiaphragmatic pressures generated at various baseline lung volumes, from residual volume to 90% of total lung capacity, were recorded before and after the induction of diaphragm exhaustion. At all levels of lung volume, aminophylline did not have an effect on the contractility of the fresh diaphragm. In the exhausted diaphragm, however, the pressure values, induced by sniffs and twitch stimulations, were significantly improved by aminophylline. This positive effect on diaphragm contractility was also impressive at 60, 75, and 90% of total lung capacity. This indicates that aminophylline significantly improves the contractile function of the exhausted human diaphragm, even if the muscle fibers are shorter than optimal. This effect occurs regardless of the neuronal firing rate, whether it is low (twitch stimulation) or high (sniff maneuver). PMID- 8004312 TI - Long-term effects of two different ventilatory modes on oxygenation in acute lung injury. Comparison of airway pressure release ventilation and volume-controlled inverse ratio ventilation. AB - A total of 18 patients with acute lung injury (ALI) were sequentially ventilated with two different modes of mechanical ventilation, each applied for a period of 24 h: (1) volume-controlled inverse ratio ventilation (VC-IRV), (2) airway pressure release ventilation (APRV). The individual sequence of both ventilatory modes was randomized. Ventilatory minute volume was adjusted for a PaCO2 of 35 to 45 mm Hg at the beginning of the study during the first ventilatory mode and then kept constant within preset limits. Hemodynamic variables were stable and similar during the 24-h periods of VC-IRV and APRV as well. Despite the lower sedation and spontaneous breathing during APRV, oxygen uptake was similar during both ventilatory modes. During the 24-h period of VC-IRV there was no relevant change of either airway pressures, alveolo-arterial O2 tension difference (AaDO2)/fraction of inspired oxygen (FIO2) or venous admixture. In contrast, peak airway pressures (Pawmax) during APRV were significantly lower (about 30%; p < 0.01), and decreased further within 24 h (p < 0.05). During APRV AaDO2/FIO2 and venous admixture improved significantly with time after more than 8 h (AaDO2/FIO2: 487 versus 414 mm Hg; p < 0.01; venous admixture: 20.6 versus 13.9%; p < 0.01; medians of onset versus end). The improvement was significantly different between both ventilatory modes (p < 0.01). We conclude that this indicates a progressive alveolar recruitment over time during ventilation with APRV.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8004313 TI - Extracorporeal carbon dioxide removal technique improves oxygenation without causing overinflation. AB - Extracorporeal CO2 removal combined with low frequency positive pressure ventilation (ECCO2R-LFPPV) improves gas exchange and decreases peak pressures, respiratory rates, and tidal volumes in animals and in humans. Recent evidence suggests that pulmonary barotrauma results from lung overinflation rather than from high pressures. This study was to test the hypothesis whether ECCO2R-LFPPV could improve gas exchange without causing lung overinflation, despite the use of higher levels of PEEP, when compared with conventional mechanical ventilation. Eleven patients with severe adult respiratory distress syndrome (ARDS) who failed to respond to different modes of mechanical ventilation were treated with ECCO2R LFPPV. Risk of pulmonary barotrauma was evaluated by static pressure-volume (P-V) curves and dynamic changes in volumes monitored by respiratory inductive plethysmography (Respitrace). ECCO2R-LFPPV PaO2/FIO2 increased from 79 +/- 21 to 207 +/- 108 (p = 0.003). Risk of barotrauma, as shown by the shape of the P-V curve, was present in all patients receiving mechanical ventilation even though most of them were treated with permissive hypoventilation. By contrast, no evidence of persistent lung overinflation could be detected by either static P-V curves or dynamic measurements in nine of 11 patients who were treated by ECCO2R LFPPV. The two remaining patients had severe airway obstruction because of bleeding, and they remained ventilated with persistent risk of barotrauma. We conclude that ECCO2R-LFPPV improves gas exchange without causing lung overinflation in a majority of patients with ARDS. PMID- 8004314 TI - Effects of inspired carbon dioxide on ventilation-perfusion matching in normoxia, hypoxia, and hyperoxia. AB - We studied the effect of low concentrations (2 to 4%) of inspired CO2 on gas exchange and ventilation-perfusion (VA/Q) relationships in healthy normocapnic anesthetized dogs during constant mechanical ventilation by the multiple inert gas elimination technique (MIGET). One group was studied at normal tidal volumes (12 to 14 ml/kg) and rates (13 to 15/min) in normoxia, and the other in mild hyperoxia (FIO2 = 0.50) and hypoxia (FIO2 = 0.15). In normoxic dogs there were progressive increases in arterial PO2 and reductions in the alveolar-to-arterial PO2 and arterial-to-mixed expired PCO2 differences in response to increases in FICO2. This increased gas exchange efficiency was characterized by reductions in both dead space ventilation and VA/Q mismatch. Better VA/Q matching was characterized by reduction in the log standard deviation of ventilation (log SDV) without significant change in the log standard deviation of perfusion (log SDQ). Gas exchange parameters returned to baseline when dogs were returned to CO2-free inspired gas. In the second group, the effects of 3% inspired CO2 were of comparable magnitude in both mild hypoxia and hyperoxia. In this group (taking hyperoxic values as baseline), there were improved gas exchange and less VA/Q heterogeneity with inspired hypoxia, both with and without inspired CO2. In contrast to the effects of added inspired CO2, improved VA/Q matching with hypoxia was characterized by reductions in both log SDV and log SDQ.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8004315 TI - Pulmonary function abnormalities in thalassemia major and the role of iron overload. AB - To determine the predominant abnormality of pulmonary function in patients with thalassemia major (TM), we evaluated 29 patients with TM who were receiving hypertransfusion therapy and chelation with desferrioxamine (DFO), and who ranged in age from 6 to 40 yr (mean 19.8 +/- 8.5 yr). A reduction in the total lung capacity (TLC) was the most striking abnormality, found in 21 of 29 patients (79%). Fourteen of these patients (67%) had a moderate or severe reduction in TLC. Expiratory flow rates, FEV1, and FEF25-75 were decreased below predicted values in 48 and 17% of the patients, respectively, but no patients had pure obstructive disease. Significant hypoxemia (oxygen saturation of less than 95%) was observed in only one patient. There was a significant inverse correlation between TLC and patient age (p < 0.003), transfusional iron burden (p < 0.003) and DFO ratio (p < 0.024). Restrictive disease is the predominant abnormality of pulmonary function in TM, with a mixed restrictive-obstructive pattern in a small number of patients. The restrictive disease becomes more severe with increasing age, and the degree and duration of iron overload appear to be important in its pathogenesis. The role of DFO therapy in preventing the pulmonary complications associated with TM requires further study. PMID- 8004316 TI - Pathophysiologic correlations in lymphoid interstitial pneumonia. AB - Effective alveolar volume, diffusing capacity for carbon monoxide (DCOsb), volume corrected diffusing capacity (D/VA), static lung compliance (Cst), and lung distensibility were measured in 16 sheep seropositive for maedi-visna virus (MVV) immediately before they were killed. Lungs were inflation-fixed, and the left lung was randomly sampled for morphometric analysis. The total lung weight, total fixed lung volume, volume densities of tissue (Vvt) and air (Vva), and the alveolar surface density were measured and correlated with the physiologic measurements. The density of surface forces could not account for the variation in the distensibility of the lungs, indicating that tissue-related forces may be important in determining lung distensibility in lymphoid interstitial pneumonia (LIP) associated with MVV infection. Possible sources of tissue-related forces are the contractile tissue associated with lung parenchyma, airways, or vasculature. When DCOsb was corrected for volume, a strong negative correlation with Vvt was noted, indicating that factors distinct from lung-volume reduction are important in limiting gas exchange in LIP associated with MVV infection. More sheep demonstrated abnormal D/VA values than any other physiologic measurement, with reduced values being apparent even in sheep considered clinically normal and with little or no morphometric evidence of lung disease. Measurements of diffusing capacity are thus considered the most sensitive functional index of disease progression. PMID- 8004317 TI - Fibrosing alveolitis associated with systemic sclerosis has a better prognosis than lone cryptogenic fibrosing alveolitis. AB - Fibrosing alveolitis associated with systemic sclerosis (FASSc) is considered to be histologically and radiologically indistinguishable from lone cryptogenic fibrosing alveolitis (CFA). To date, the natural history of the two diseases has not been compared directly in large groups of patients followed at a single institution. We evaluated the survival of 205 patients with CFA and 68 patients with FASSc. Deaths during the follow-up period were reported in 142 patients with CFA (70%) and in 11 patients with FASSc (16%). Unadjusted survival from the onset of dyspnea was less in CFA than in FASSc (odds ratio, 3.3; p < 0.001); this difference persisted after adjustment for age of onset of dyspnea and smoking history. Survival from presentation was less in CFA (odds ratio approximately 3.3) after adjustment for age of presentation, smoking history, and initial pulmonary function indices. These differences persisted when analysis was confined to patients with histologic confirmation of fibrosing alveolitis and after adjustment for treatment. In patients undergoing computed tomography (CT) of the lungs, survival was less in CFA after adjustment for extent of abnormal lung on CT and CT pattern of disease (odds ratio, 3.9; p < 0.001). These findings indicate that despite their histologic and radiologic similarities, lone CFA and FASSc have different courses. PMID- 8004318 TI - Pulmonary disease associated with the human immunodeficiency virus in Kigali, Rwanda. A fiberoptic bronchoscopic study of 111 cases of undetermined etiology. AB - All human immunodeficiency virus type 1 (HIV-1) infected adult patients referred to the Division of Pulmonary Diseases of the Centre Hospitalier de Kigali, Rwanda for evaluation of a pulmonary disease of undetermined etiology (PDUE) were investigated by fiberoptic bronchoscopy using both bronchoalveolar lavage (BAL) and transbronchial biopsy (TBB). During a 10-mo period 111 HIV-1 infected patients with PDUE were examined, of whom 47 (42%) fulfilled the World Health Organization (WHO) clinical case definition for acquired immunodeficiency syndrome (AIDS) and seven (6%) had an AIDS-defining illness. Nonspecific interstitial pneumonitis was diagnosed in 42 (38%) patients, tuberculosis in 25 (23%), cryptococcosis in 14 (13%), Kaposi's sarcoma (KS) in 10 (9%), Pneumocystis carinii pneumonia (PCP) in five (5%). The diagnosis remained undetermined in 18 (16%) patients. Chest radiograph patterns were generally nonspecific. TBB and BAL had diagnostic yields of 82 and 26% of all final diagnoses, respectively. Our study on Rwandese HIV-1-infected patients with PDUE provides evidence for a large spectrum of pulmonary diseases with relative frequencies differing strikingly from those in developed countries. Detailed investigations confirm the rarity of PCP in Africa and highlight nonspecific interstitial pneumonitis as the predominant diagnosis of PDUE. Empiric antituberculosis treatment is justified in the absence of clinical manifestations suggestive of a specific diagnosis and while awaiting the results of the diagnostic procedures. Primary prophylaxis for PCP would not be appropriate in Africa. PMID- 8004319 TI - Boosting of tuberculin sensitivity among Southeast Asian refugees. AB - Following an initial negative Mantoux tuberculin skin test, a second test, given as soon as 1 wk later, has been shown to elicit markedly larger reactions (boosting) in 20 to 40% of refugees tested in the United States. We conducted a study to determine the explanation for this phenomenon. Using the Mantoux method of intradermal skin testing, 2,469 refugees from Southeast Asia were initially tested with tuberculin followed by sequential retesting 7 and/or 90 d later. They were also tested initially with nontuberculous mycobacterial antigens. A high proportion (35.5%) of Southeast Asian refugees had reactions (> or = 10 mm induration) to an initial tuberculin test, and 30.9% of the nonreactors exhibited boosting on a subsequent tuberculin test. Boosting, unlike reactivity to the initial tuberculin test, was not associated with exposure to a person with tuberculosis. However, boosting was associated with reactivity to nontuberculous mycobacterial antigens and a history of bacille Calmette-Guerin (BCG) vaccination. Boosting in this population is therefore attributable to environmental exposure to nontuberculous mycobacteria that are endemic in Southeast Asia or to BCG vaccination, rather than to remote infection with Mycobacterium tuberculosis. Sequential tuberculin screening and preventive therapy of persons with boosted reactions is not recommended as a tuberculosis prevention strategy in this population. PMID- 8004320 TI - Hemodynamic effects of nasal and face mask continuous positive airway pressure. AB - Studies of the hemodynamic effects of nasal continuous positive airway pressure (n-CPAP) in normal subjects have had conflicting results. The largest study (n = 19) found no effect of up to 15 cm H2O on heart rate (HR), cardiac stroke volume (SV), or cardiac index. We hypothesized that n-CPAP, by increasing intrathoracic pressure, should decrease SV and cardiac output (CO) in a dose-dependent fashion in normal subjects. We also hypothesized that mouth position, i.e., open or closed, could affect intrathoracic pressure and thus SV and CO. Six normal subjects were tested with four levels of CPAP (5, 10, 15, and 20 cm H2O) under three mask conditions-face mask and nasal mask with the mouth open (mo) or with the mouth closed (mc). Noninvasive pulsed Doppler measurements of SV and HR were made under each condition. N-CPAP (mc) and face mask CPAP (f-CPAP) resulted in significant dose-dependent decreases of SV-24 +/- 5 ml (21%) and 33 +/- 5 ml (28%), respectively--from baseline to 20 cm H2O (p < 0.05). HR were unchanged and CO significantly decreased with n-CPAP(mc) and with f-CPAP, 1.6 +/- 0.38 L/min (23%) and 2.29 +/- 0.54 L/min (31%), respectively, from baseline to 20 cm H2O (p < 0.05). Esophageal pressure measurements verified increasing intrathoracic pressure with increasing levels of f-CPAP and n-CPAP (mc) but not with n-CPAP (mo). In conclusion, n-CPAP (mc) and f-CPAP resulted in significant and similar dose-dependent decreases in SV and CO. PMID- 8004321 TI - Composition of human pulmonary surfactant varies with exercise and level of fitness. AB - We have tested the hypothesis that the composition of alveolar surfactant varies with pattern of breathing and level of fitness. We examined three major components of surfactant, surfactant protein A (SP-A), disaturated phospholipids (DSP), and cholesterol (CHOL) in bronchoalveolar lavage (BAL) fluid from 12 healthy men before and after exercise. Fitness was assessed as work load/heart rate ([kpm.min-1]/[HR.HRmax-1]) achieved during cycling for 30 min at 90% theoretical maximal heart rate. Using a bronchoscope, four 20-ml vols of 0.15 M NaCl at 37 degrees C were instilled and then recovered from first a right upper and then a right lower lobe segmental bronchus. As we found no differences in the BAL from upper and lower lobes, the fluid was combined. We found a direct relationship between CHOL and DSP (rs = 0.84, p < 0.001), SP-A and CHOL (rs = 0.40, p < 0.025), and between SP-A and DSP (rs = 0.44, p < 0.025). The change in the ratios CHOL/DSP, SP-A/CHOL, and SP-A/DSP immediately after exercise was correlated with fitness (rs = -0.56, p < 0.025; rs = 0.75, p < 0.005; rs = 0.62, p < 0.025, respectively). We conclude that the composition of surfactant can change rapidly with exercise in a manner related to fitness, and we suggest that this is consistent with the existence of at least two pools of tissue surfactant of different composition supplying the alveolar compartment. PMID- 8004322 TI - Chronic platelet-activating factor induces a decrease in pulmonary vascular compliance, hydroxyproline, and loss of vascular matrix. AB - We have previously demonstrated that chronic intravenous platelet-activating factor (PAF) induces morphologic remodeling of pulmonary arteries characterized by a decrease in internal and external elastic lamina circumference, pulmonary arterial contracture, and internal elastic lamina duplication. The mechanism of PAF-induced arterial contracture is unknown. In this study we determined whether PAF caused arterial contracture through cell loss by calculating the number of cell nuclei/total cross-sectional area of arteries. The nuclear ratio was increased in intra- and preacinar pulmonary arteries of PAF-treated rabbits. Hydroxyproline content of lungs stratified by anatomic region was significantly reduced in intra-acinar tissue of PAF-treated rabbits, indicating that PAF induced vascular contracture was associated with loss of interstitial collagen. We next tested whether these morphologic alterations were associated with decreased pulmonary vascular compliance and increased resistance. Compliance and resistance were determined in isolated, perfused lungs from rabbits chronically treated with PAF. Compliance was calculated: (1) from the slope of the venous occlusion trace (CVO), (2) by increasing left atrial pressure (CLA), (3) by increasing flow (CHF), and (4) by the classic static technique (CAV) of adding volume (2 ml) to a passively drained lung. Vascular compliance was significantly reduced in PAF-treated lungs when measured by all four methods; however, pulmonary vascular resistance was unchanged. We conclude that structural changes that result from chronic intravenous PAF infusion affect the elastic modulus to a greater extent than factors that influence pulmonary vascular resistance. PMID- 8004323 TI - Paraaminosalicylate blocks that ileal injury induced by phorbol myristate acetate. AB - Activation of neutrophils with the release of oxidant radicals has been implicated in the pathogenesis of gut injury in inflammatory bowel disease (IBD). The pathogenesis of gut injury in the multiple organ dysfunction syndrome associated with acute lung injury, although less focal, appears to be similar. Paraaminosalicylate (PAS) has been shown to be effective in treating IBD, most likely because of its ability to scavenge oxidant radicals. The present study was therefore designed to test the hypothesis that PAS attenuates the gut injury typically seen during systemic neutrophil activation by phorbol myristate acetate (PMA). We assessed gut injury by measuring the concentration ratio of lymph to plasma protein (CL/CP) at steady-state lymph flows in autoperfused cat ileum preparations. As expected, the CL/CP increased in animals given PMA (15 micrograms/kb; n = 6) compared with control animals (n = 5) (0.205 +/- 0.033 versus 0.118 +/- 0.004; p = 0.04) 0.04) and were accompanied by morphologic alterations. In contrast, the intravenous administration of PAS (100 mg/kg) to animals prior to PMA infusion (n = 5) yielded a CL/CP value indistinguishable from that in control animals (0.113 +/- 0.017 versus 0.118 +/- 0.004). Additional in vitro studies suggested that the protective effects of PAS were not the result of altered neutrophil margination, chemotaxis, or oxidant burst. Although PAS appeared to protect the ileum from PMA-induced microvascular injury, it had no protective effects on the lungs. PMID- 8004324 TI - The bacteriology of obstructive pneumonitis. A prospective study using ultrasound guided transthoracic needle aspiration. AB - Obstructive pneumonitis, the opacity that develops distal to an obstructing endobronchial lesion or external compression, is actually a combination of atelectasis, bronchiectasis with mucus plugging, and true parenchymal inflammation. In the majority of cases, it is usually not possible to determine whether infection is present or not from the radiographic findings alone. The aim of this study was to evaluate the bacteriology of obstructive pneumonitis and the influence of this result on the treatment of patients. From March 1992 to February 1993, 26 consecutive patients (20 men and six women) with obstructive pneumonitis were investigated. The obstructive pneumonitis had been caused by malignant tumors in 24 and benign lesions in two. Chest ultrasound (US) and US guided percutaneous transthoracic aspirations were undergone to obtain specimens for microbiologic examination. Microorganisms were isolated from seven of nine febrile patients and two of 17 nonfebrile patients. A total of 16 bacterial strains are detected in obstructive pneumonitis (Pseudomonas aeruginosa, Klebsiella pneumoniae, viridant streptococci, Bacteroides fragilis, two Peptostreptococcus species, Mycobacterium tuberculosis, Pseudomonas maltophilia, Streptococcus sanguis, Staphylococcus aureus, Bacteroides thetaiotamomicrons, Bacteroides intermedius, Bacteroides species, Veillonella species, aerobic gram positive bacilli, and Escherichia coli). In five cases the isolates were monobacteriae, and in the remaining four cases, cultures yielded more than one bacteria. The results of aspirate cultures led to changes in the initial antibiotic trial in seven of nine patients, and fever subsided thereafter. Pneumothorax occurred in one cases as the sole complication. The pathogen causing obstructive pneumonitis is very heterogeneous, and polymicrobial infection is common.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8004325 TI - Nontuberculous mycobacteria. An underappreciated cause of geriatric lung disease. AB - Nontuberculous mycobacteria (NTM) infection is a frequent opportunistic infection in patients infected with the human immunodeficiency virus. However, NTM infection may also occur in nonimmunocompromised hosts. In order to determine the spectrum of mycobacterial infection in the nonacademic setting, we analyzed the demographic and clinical characteristics of all patients presenting to a suburban multispecialty clinic during a 24-mo period. Twenty-one patients presented with active mycobacterial lung infections during the study period. Of these, only one had Mycobacterium tuberculosis. The remaining 20 had lung infections with NTM. One patient was infected with M. kansasii, three had M. abscessus, and 16 had M. avium complex. One patient with disseminated M. avium infection met the diagnostic criteria for the acquired immunodeficiency syndrome. The remaining 19 were largely normal at presentation and were predominantly elderly (mean age, 71 +/- 11 yr), female (79%), nonsmokers (89%) who presented with cough (94%) and localized radiographic infiltrates (84%), often in the right middle lobe and/or lingula (73%). The predominance of nontuberculous mycobacteria over M. tuberculosis in our practice was mirrored by results of an 11-yr review of experience from a nearby suburban hospital, where 65% of mycobacterial infections in the previous 5 yr were with NTM. We conclude that infection with NTM represents a previously underappreciated cause of chronic lung infection among elderly middle-class patients in the community setting. PMID- 8004326 TI - Gastroesophageal reflux with nasogastric tubes. Effect of nasogastric tube size. AB - Pulmonary aspiration of gastric contents results initially from reflux of stomach contents into the esophagus. Small-bore enteral feeding tubes are thought to result in less pulmonary aspiration and less reflux. We prospectively investigated the effect of nasogastric tube size upon gastroesophageal (GE) reflux in normal volunteers in a randomized crossover trial. Reflux was assessed by gastroesophageal scintiscanning, a radioisotopic technique that detects and quantitates GE reflux. A total of 11 subjects were studied three times: control, no nasogastric tube, small-bore (8F) nasogastric tube, and large-bore (14F) nasogastric tube. Reflux was assessed in each subject under each experimental condition by provocative testing in which abdominal pressure was increased from 0 to 100 mm Hg by 20-mm Hg increments with an abdominal pressure device. GE reflux indices were calculated for each measurement and the groups compared. A positive indicator of reflux was defined as a > or = 4% reflux index. Gastroesophageal reflux was not detected at any level of abdominal pressure regardless of the presence or size of a nasogastric tube. With maximum 100 mm Hg abdominal pressure, the reflux index was control, 1.75 +/- 0.45%; small-bore tube, 1.67 +/- 0.28%; and large-bore tube, 1.88 +/- 0.35% (NS). The reflux index was not different between small-bore and large-bore nasogastric tubes. Our data suggest the size of a nasogastric tube is not an important determinant of GE reflux in normal subjects during short-term intubation. Large-bore tubes did not cause more reflux than small-bore tubes. The presence of a nasogastric tube did not cause reflux in normal subjects. These data suggest that factors other than the size of nasogastric tube are more important in GE reflux in normal subjects. PMID- 8004327 TI - Recovery of airway structure and function after hyperoxic exposure in immature rats. AB - We have previously demonstrated that hyperoxic exposure (> 95% O2 for 8 d) induces airway cholinergic hyperresponsiveness and remodeling in 21-d-old rats. To examine the potential relationship between airway hyperresponsiveness and remodeling in these animals, we exposed rats to air or hyperoxia for 8 d, returned them to air-breathing, and measured airway responsiveness to inhaled acetylcholine (ACh) and layer thicknesses immediately after or 16 or 48 d after cessation of air or O2 exposure. The ACh concentration required to increase resistance by 100% (EC200ACh) was calculated by linear interpolation. Small airway (circumference < 1,000 microns) and medium-sized, conducting airway (1,000 to 3,000 microns) epithelial and smooth muscle layer mean thicknesses and fractional areas (layer area/luminal cross-sectional area) were determined from lung sections by contour tracing using a digitizing pad and computer. As we reported previously, after 8 d of O2 exposure, group mean log EC200ACh was significantly reduced relative to that in control animals (p < 0.001). Similarly, hyperoxic exposure was associated with significant increases in all parameters of airway layer thickness assessed (p < 0.05). However, by 16 d after cessation of O2 exposure, there were no longer statistically significant differences in log EC200ACh, airway layer thickness, or fractional area between control and O2 exposed animals. Further studies, in a second cohort of animals killed 0, 3, 6, 8, or 13 d after cessation of O2 exposure, demonstrated progressive reductions in small airway epithelial and smooth muscle layer thicknesses, confirming that hyperoxia-induced airway remodeling resolves by approximately 2 wk after termination of O2 exposure.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8004328 TI - Rapidly progressive bronchiolitis obliterans with organizing pneumonia. AB - Bronchiolitis obliterans with organizing pneumonia (BOOP) is a distinct clinical pathologic syndrome. Most patients experience a good response to therapy, and death from progressive BOOP is uncommon. This report describes the clinical features, etiologic factors, pathologic findings, and outcome of 10 patients with rapidly progressive BOOP that was characterized by severe respiratory failure. The major clinical manifestations were dyspnea, cough, fever, crackles on chest examination, and hypoxemia at rest. Underlying conditions or exposures included connective-tissue disease, exposure to birds, and chronic nitrofurantoin therapy. All patients had the characteristic histopathologic findings of BOOP. However, at autopsy in six patients, the predominant histologic pattern was that of alveolar septal inflammation and fibrotic honeycombing. Seven patients died and three patients survived but had persistent pulmonary dysfunction despite aggressive care. In two patients BOOP has progressed, with severe chronic respiratory decompensation. Thus, there is a subset of patients with BOOP who present with a fulminant course leading to death or chronic severe fibrosis and marked impairment of lung function. In addition, the histologic picture of BOOP may be a manifestation of early lung injury that can resolve or progress rapidly to alveolar septal inflammation, end-stage fibrosis, and honeycombing. PMID- 8004329 TI - Persistent asthma after repeated exposure to high concentrations of gases in pulpmills. AB - This is a clinicopathologic study of three subjects with irritant-induced asthma. They were pulpmill workers who had a history of multiple "gassing" episodes that occurred over a period of years. Persistent symptoms of asthma and nonspecific bronchial hyperresponsiveness and/or variable airflow obstruction occurred after at least one episode of "gassing," resulting in symptoms severe enough to require emergency room treatment. One of the three subjects had normal spirometry values before he entered the pulpmill. Bronchial biopsy done on these subjects showed changes compatible with asthma, including thickened basement membrane in two and cellular infiltration with activated eosinophils and mononuclear cells in all three. The results of immunohistology of bronchial mucosal biopsy of these subjects were compared with those of patients with allergic asthma and patients with Western red cedar-induced asthma. Subjects with irritant-induced asthma had a greater density of activated eosinophils and fewer T-lymphocytes, suggesting that cell-mediated immune mechanisms are not involved in the pathogenesis of this condition. PMID- 8004331 TI - Acute respiratory failure in patients treated for babesiosis. AB - Babesiosis is a tick-borne protozoal disease with infrequent clinical complications. We report three cases of noncardiogenic pulmonary edema in patients from Nantucket Island, MA, with a history of Lyme disease and review the clinical presentation of babesiosis and its treatment. Respiratory complications in our patients, as well as in the four previously reported cases in the literature, occurred a few days after initiation of medical therapy. We hypothesize that the pathophysiology of the pulmonary edema is multifactorial, due to decreased deformability of the infected erythrocytes, increased cytoadherence of red blood cells in capillaries and venules, and a possible role of excessive production of certain cytokines, such as tumor necrosis factor and interleukin-1. PMID- 8004330 TI - Soluble TNF receptors (TNF-sR55 and TNF-sR75) in lung allograft recipients displaying cytomegalovirus pneumonitis. AB - Two distinct types of tumor necrosis factor receptors (TNF-R) have been identified (TNF-R55 and TNF-R75). Both TNF-R also exist in soluble forms (TNF sR), resulting from the release of the extracellular domains (TNF-sR55 and TNF sR75). TNF-sR may play an important role in vivo as they can bind to TNF alpha and prevent ligand binding to the cellular TNF-R, thus acting as naturally occurring inhibitors of TNF alpha. Sera from lung allograft recipients with cytomegalovirus (CMV) pneumonitis (12 patients) were assayed for TNF-sR55 and TNF sR75. The concentrations were compared with those from either control lung recipients displaying neither rejection nor infection (12 patients), or lung recipients with allograft rejection (12 patients). Serum TNF-sR55 and TNF-sR75 concentrations were measured by enzyme-linked immunologic binding assay. Serum TNF-sR55 and TNF-sR75 concentrations were significantly higher during CMV pneumonitis (mean +/- SEM: 13.7 +/- 4.7 ng/ml, and 11.7 +/- 2.7 ng/ml, respectively) than during allograft rejection (3.7 +/- 0.3 ng/ml, p < 0.001, and 2.6 +/- 0.6 ng/ml, p < 0.001, respectively). They were also higher than in control subjects (3.6 +/- 0.3 ng/ml, p < 0.001, and 1.9 +/- 0.5 ng/ml, p < 0.001, respectively). Serum TNF alpha concentration was low in case of rejection or in control subjects (< 20 pg/ml). Conversely increased levels of TNF alpha were detected in the serum of six out of the 12 patients with CMV pneumonitis (p < 0.03 versus rejection and control subjects). Ganciclovir treatment of CMV pneumonitis led to a dramatic decrease of TNF alpha, TNF-sR55, and TNF-sR75 serum levels.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8004333 TI - [Burnout in students of a nursing school. Results of a study and considerations on prevention by redesigning the training]. PMID- 8004332 TI - Hantavirus pulmonary syndrome. PMID- 8004334 TI - [Burnout measurement. Study of a German version of the Maslach Burnout Inventory (MBI-D)]. PMID- 8004335 TI - [The burn-out syndrome in nursing. An empirical study in a sociopsychological context]. PMID- 8004336 TI - [Therapeutic mandate and relationary work in nursing]. PMID- 8004337 TI - [Leading discussions in nursing education]. PMID- 8004338 TI - [Problems in the nursing of patients with aphasia]. PMID- 8004339 TI - [Aphasic disorders]. PMID- 8004340 TI - [What promotes, what prevents anxiety? Psychological aspects in conversations preceding surgery]. PMID- 8004341 TI - [Communication and a guidance style oriented towards the coworkers]. PMID- 8004342 TI - [The language of the dying]. PMID- 8004343 TI - [The normal development of language]. PMID- 8004344 TI - [Language development in children with hearing loss]. PMID- 8004345 TI - [Partial restraint of a patient. Problems of delimitation between nursing service and medical service]. PMID- 8004346 TI - [Patient care planning is a chance]. PMID- 8004347 TI - [Home care: the free market is leaning on the weak. The "flight from the institutions" drives many nurses to ambulatory services]. PMID- 8004348 TI - [Co-workers are turning into co-managers]. PMID- 8004349 TI - [Strategic personnel development in the hospital]. PMID- 8004350 TI - [The hospital as a technical trap]. PMID- 8004351 TI - [Time measurements in nursing: validity, reliability, reasonableness]. PMID- 8004352 TI - [Between service planning and shift planning]. PMID- 8004353 TI - [The nuisance of supervision]. PMID- 8004354 TI - [The nursing education of civilian service workers]. PMID- 8004355 TI - [Nursing courses: a start into a dead end?]. PMID- 8004356 TI - [The future of short-term care]. PMID- 8004357 TI - [Assistance for self-help as a program. The Langenhagen Geriatric Rehabilitation Facility has been active for 15 years]. PMID- 8004358 TI - Polyenylphosphatidylcholine improves the lipoprotein profile in diabetic patients. AB - Patients with diabetes mellitus commonly exhibit pathological lipoprotein profiles and concomitant cardiovascular or peripheral atherosclerotic complications. Thirty non-insulin-dependent diabetics with secondary hyperlipidemia received 2.7 g 3-sn-polyenylphosphatidylcholine (PPC) or placebo daily, orally over a 2-month period under randomized, double-blind trial conditions, to investigate the efficacy and tolerance of the treatment. This period was followed by a one-month observation phase without investigational medication. Serum LDL cholesterol, total cholesterol, HDL cholesterol and triglycerides were determined on days 1, 14, 28, 56 and 84. After 56 days of treatment with PPC, the primary variable of effectiveness, LDL cholesterol, decreased significantly (p = 0.0174) by 17% from 191 +/- 31 to 159 +/- 36 mg/dl, whereas values did not change in the placebo group. Total cholesterol (TC) in serum decreased by 16% from 303 +/- 22 to 255 +/- 23 mg/dl with PPC. In the placebo group, only a slight decrease from 292 +/- 27 to 289 +/- 41 mg/dl occurred. Mean serum triglyceride (TG) levels fell by 9% from 194 +/- 32 to 177 +/- 27 mg/dl in the PPC group. In the control group, values increased from 193 +/ 34 to 202 +/- 41 mg/dl. The differences in LDL, TC and TG between the treatment groups were statistically significant; p = 0.0014, p = 0.0001 and p = 0.007, respectively. HDL cholesterol in serum increased 12% from 50 +/- 10 to 55 +/- 13 mg/dl after PPC application. The control group did not show any alteration of mean HDL cholesterol level at any time.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8004359 TI - Lack of effect of Chinese medicines on bioavailability of ofloxacin in healthy volunteers. AB - Recently, Chinese medicines have become available as OTC drugs and are frequently prescribed with Western medicine for the treatment of various chronic diseases. In this study, the effect of the Chinese medicines Sho-saiko-to (TJ-9), Rikkunshi to (TJ-43) and Sairei-to (TJ-114) on the bioavailability of ofloxacin (OFLX) was investigated in seven volunteers in an open, random crossover fashion. Subjects received a single oral dose of OFLX (200 mg) alone and with coadministrations of each Chinese medicine, at one-week intervals. Plasma and urine samples were analyzed by high-performance liquid chromatography. No significant differences in any estimated bioavailability parameters of OFLX were observed between the two phases. The urinary recovery of OFLX excreted within 24 h after the administration of OFLX alone, 80.6 +/- 3.9% (mean +/- SEM), was not significantly different from those after the coadministrations of the Chinese medicines (79.7 +/- 5.1% for TJ-9, 76.8 +/- 2.3% for TJ-43 and 80.3 +/- 5.3% for TJ-114), suggesting that there was no difference in the systemic availability of the four doses. These findings indicate that the Chinese medicines studied have no significant effect on the rate and extent of bioavailability of OFLX. PMID- 8004360 TI - Pharmacokinetics and bioavailability of bemoradan, a long-acting inodilator in healthy males. AB - Bemoradan is a potent, long-acting orally active inodilator. The pharmacokinetics and bioavailability of bemoradan were studied in twelve normal males following oral administration of single, ascending doses of the bemoradan HCL salt in capsules. Plasma and urine levels of bemoradan were determined by HPLC (detection limits: approximately 0.5 ng/ml for plasma and 5 ng/ml for urine). Bemoradan was rapidly absorbed from the capsule formulation at all doses (Cmax occurred at 2.1 2.4 hours). Bemoradan was slowly eliminated from the body (harmonic mean t1/2 16 23 hours). There was a dose-proportional increase in the AUC (0-48) values of bemoradan in humans following the administration of 0.5, 1, 1.5 and 2 mg of bemoradan. The AUC (0-48) values increased to 2.3, 3.4 and 4.0 times when the dose was increased to 2, 3 and 4 times. Urinary excretion of unchanged bemoradan accounted for approximately 5-12% of the dose. Results from this study and previous studies in rats and dogs indicate that bemoradan is well and rapidly absorbed after oral dosing, has linear pharmacokinetics and long elimination half lives across species. PMID- 8004361 TI - Angiotensin converting enzyme inhibitor-induced renal dysfunction: recommendations for prevention. AB - The angiotensin converting enzyme inhibitors constitute a major treatment modality for cardiovascular diseases, including congestive heart failure and hypertension. In addition to their beneficial hemodynamic effects, they offer other advantages, such as a relative lack of adverse effects on other cardiovascular risk factors. When used judiciously, the angiotensin converting enzyme inhibitors may also contribute to improved renal function. These agents induce vasodilation of both efferent and afferent renal vessels, which may facilitate improved renal blood flow and glomerular filtration rate in individuals whose renal insufficiency results from hyperadrenergic activity. Improvements in renal function may also be observed when angiotensin converting enzyme inhibitors are employed in other clinical conditions, such as diabetic nephropathy or proteinuric renal disease. Although the renal protective effects of the angiotensin converting enzyme inhibitors are well recognized, their use in certain circumstances may actually contribute to renal dysfunction. The factors which may predispose an individual to angiotensin converting enzyme inhibitor induced renal dysfunction must be recognized by the clinician and appropriate interventions taken to prevent this potentially deleterious effect. This article reviews those factors which increase risk for angiotensin converting enzyme inhibitor-induced renal dysfunction and provides recommendations for prevention. PMID- 8004362 TI - Indicative therapeutic and toxic drug concentrations in plasma: a tabulation. AB - The table presented provides the therapeutic, toxic and lethal serum concentrations (to the extent demonstrable) of drugs. The use of plasma levels when administering drugs increases the likelihood of attaining a therapeutic response and serves to minimize the toxicity. The therapeutic range of agents should be used as a guideline and must be interpreted in conjunction with other monitoring parameters. PMID- 8004364 TI - Evaluation of lung tissue and hilar lymph node concentrations of azithromycin. AB - Since it is believed that most infections occur in the interstitial fluid, it has been suggested to measure the concentration of antimicrobial agents in pulmonary lymph that reflects the extracellular, extra-blood-vascular milieu in the lung. The aim of this study was to investigate the lung tissue and pulmonary lymph node penetration of azithromycin after 500 mg daily oral administration for three days in patients undergoing open thoracotomy. At the end of the treatment, each subject was assigned for 5 groups of 5 patients each according to thoracotomy time after the last dose (24, 48, 96, 120 and 144 h). Azithromycin was assayed by an agar diffusion method with Sarcina lutea Z114 (DRH) used as the test organism and the Antibiotic Assay Medium 1, pH 8.5 used as the medium. All patients had a detectable concentration of azithromycin in serum 24 h after the last dose (72 h after the first dose); the concentration fell below the detection limit (0.01 mg/l-1) after 96 h (168 h after the first dose). Peak concentrations in lung tissue and lymph nodes were found after 48 h (96 h after the first dose). Tissue and lymph node concentrations of azithromycin were much greater than serum concentrations and these tissue and lymph node concentrations persisted after serum concentrations declined. The concentrations in lung tissue of azithromycin were always higher than corresponding concentrations in hilar lymph nodes.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8004363 TI - Midazolam and ketamine as premedication in colonoscopies: a pharmacodynamic study. AB - As colonoscopy is often painful, a premedication appears to be indispensable. Commonly, benzodiazepines, i.e. midazolam, alone or in combination with analgesic drugs are used. Besides all advantages, midazolam especially is known to have the risk of oversedation and respiratory depression. Therefore it should be used at minimal dose. In a double-blind, randomized study, three premedication-schedules of midazolam (mid) plus ketamine (ket) were compared in 33 patients, aged between 8 and 60 years, with regard to safety and acceptance by patients and endoscopist. I: ket 1 mg/kg+mid 0.1 mg/kg, max. 5 mg II: ket 1 mg/kg+mid 0.05 mg/kg, max. 2.5 mg III: ket 0.75 mg/kg+mid 0.1 mg/kg, max. 5 mg Oxygen-saturation, heart rate and blood pressure were recorded as well as the evaluations of sedation, cooperation and complaint of pain. To assess the recovery-time of the patients, the reaction time and the attention were evaluated by "Wiener's determination apparatus" and "test d2", respectively, before and at 1, 2, 3 and 4 hours after premedication. Medication I resulted in heavy sedation, good cooperation and amnesia but had the strongest tendency towards hypoxemia. Under schedule III, reduced cooperation and acceptance were seen due to a strong experience of pain. The best conditions during the examination with regard to cooperation, experience of pain and acceptance were found after premedication II without relevant depression of vital parameters. It can be concluded that midazolam can be used at minimal recommended doses as premedication for colonoscopy if combined with ketamine in a sufficient analgesic dosage. PMID- 8004365 TI - Effects of lovastatin (20-80 mg daily) on lipoprotein fractions in patients with severe primary hypercholesterolemia. AB - The effect of lovastatin on lipids, lipoproteins and apolipoproteins was studied in 10 patients with primary hypercholesterolemia. After four weeks diet/placebo alone, patients received diet plus lovastatin at daily doses of 20 mg (weeks 1 4), 40 mg (weeks 5-8) and 80 mg (weeks 9-12). Twelve weeks of treatment with lovastatin resulted in a lowering of total cholesterol and LDL-cholesterol by 34% and 41%, respectively. Triglycerides and VLDL-cholesterol decreased by 19% and by 42%, respectively. HDL-cholesterol and HDL2-cholesterol increased, whereas HDL3 cholesterol was not affected. IDL-cholesterol decreased by 50%, suggesting that the clearance of remnant lipoproteins was enhanced by lovastatin. In the VLDL and the IDL fraction, the triglyceride to cholesterol mass ratio increased significantly after twelve weeks of therapy. Lipoprotein(a) was not affected. Lovastatin was well tolerated and the data shows that lovastatin exerts favorable effects on plasma lipoprotein fractions. It may, therefore, prove a useful drug in the primary and secondary prevention of atherosclerotic vessel diseases. PMID- 8004366 TI - Pantoprazole lacks interaction with antipyrine in man, either by inhibition or induction. AB - Substituted benzimidazole inhibitors of the gastric H+/K(+)-ATPase may interact with the cytochrome P450 enzyme system and alter the pharmacokinetics of coadministered drugs, as known for omeprazole. The primary aim of the present studies was to determine whether pantoprazole, a new, selective proton pump inhibitor, modifies the plasma concentrations of orally-administered antipyrine, a commonly used marker for mixed hepatic oxidase enzyme activity. In the acute study, 12 healthy male volunteers were given a) a single 30 mg i.v. doses of pantoprazole, b) a single 5 mg/kg oral dose of antipyrine, or c) coadministered pantoprazole and antipyrine according to a randomized three-period change-over design. In the chronic study, another 12 volunteers received 40 mg once-daily oral doses of pantoprazole on day 3 and on days 5-12, and a single oral 5 mg/kg dose of antipyrine on days 1, 12 and 14. Antipyrine plasma concentrations were measured without pantoprazole (day 1), on the last day of chronic dosing with pantoprazole (day 12) and 48 hours after the last dose of pantoprazole (day 14) to differentiate between inhibition and induction, respectively. Both drugs were well tolerated and no adverse events or clinically relevant alterations in vital signs or laboratory parameters were observed during treatment. The point estimates of the respective AUC- and Cmax-ratios for antipyrine with and without pantoprazole were 0.99 and 0.98 in the acute study, and 1.01 and 0.93 on day 12, and 1.04 and 0.99 on day 14 of the chronic study.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8004367 TI - [Is chorionic biopsy a dangerous and outdated method?]. AB - The authors evaluated the risk of chorion biopsy used within the framework of prenatal diagnosis of the foetus. The incidence of abortions following transabdominal CVS (0.6%) did not differ from abortions after amniocentesis in the second trimester (0.5%). In a group of 1002 diagnostic biopsies of the chorion the authors did not record in the born infants reduction deformities of the extremities. Chorion biopsies were performed in 98% between the 10th and 12th week of gestation. The incidence of mosaicism--1.59%--was not significantly higher than reported in the literature. The authors recommend: to increase the size of the sample of chorion tissue by the use of a manual aspirator, the use of a 30 ml plastic syringe or the double needle method. They consider CVS a suitable method which serves the diagnosis of IUGR and the prenatal diagnosis of the foetus before the 20th week of gestation when cordocentesis involves risk. PMID- 8004368 TI - [Pregnancy and the thyroid gland]. AB - The authors assessed, using ultrasonography, the volume of the thyroid gland in 93 women 4 days and then 3 and 6 months after parturition. The results were compared with a control group of women who were not delivered of a baby during the last 12 months. Women 4 days after delivery had on average a thyroid gland by 3.1 ml larger (P < 0.01) than controls. Three months after delivery there was still a significant difference in the volume between women who had a baby and the control group (P < 0.05). Goitre (volume larger than 22 ml) was observed after childbirth in 11 (11.8%), where as in the control group only in 3 women (5.3%). The authors analyze the causes which may bring about enlargement of the thyroid gland during pregnancy. PMID- 8004369 TI - [Postpartum thyroiditis and the contribution of ultrasonographic examination of the thyroid gland in its diagnosis during the first half-year after delivery]. AB - Changes which take place in the thyroid parenchyma of the mother from postpartum thyroiditis and which lead to a change of echogenicity can be detected by ultrasonographic examination of the thyroid gland before clinical manifestation of impaired thyroid function caused by inflammation. The authors evaluated the echogenicity of the thyroid gland in 60 women three months after delivery. From the whole group of women 47 (78.4%) had a homogenous and adequate echogenicity, 13 (21.6%) had a reduced echogenicity. A positive cytological finding, i.e. lymphocytic infiltration was found in 9 women and concurrently positive antithyroglobulin antibodies in 5 of them. During the first six months after childbirth impaired thyroid function was recorded in 4, i.e. 6.6%: 1x hyperthyroidism and 3x hypothyroidism. PMID- 8004370 TI - [Glycosaminoglycans in the peritoneal fluid of infertile women with endometriosis]. AB - The authors examined the glycosaminoglycan level in the peritoneal fluid of 54 infertile women with or without endometriosis. The peritoneal fluid was collected during a routine laparoscopic examination. Glycosaminoglycans were assayed in complexes with Alcian blue. There was a higher concentration of glycosaminoglycans in peritoneal fluid during the follicular phase of women with endometriosis. The authors did not prove a statistically significant difference between women with and without endometriosis. PMID- 8004371 TI - [Potential side-effects of oral contraception: hirsutism and hypertension]. AB - Since we observed the development of hirsutism and hypertension in a series of middle-aged women using peroral contraceptive drugs, we tried to ascertain whether there is any correlation between body mass index, blood pressure and urinary elimination of a series of steroid hormones. Although most correlations tested were statistically insignificant, we found a statistically significant correlation between the systolic blood pressure and the sum of 11 beta hydroxyandrosterone + oxoetiocholanolone + 11 beta-hydroxyetiocholanolone urinary excretion, as assessed by thin-layer chromatography of urinary 17-oxosteroids, using dansylhydrazine as a prelabelling reagent. PMID- 8004372 TI - [The first sexual intercourse in girls]. AB - The authors describe the course of the first sexual intercourse in 344 Czech girls examined at the age of 16-18 years. Attention was paid in particular to the following factors: age during first intercourse, period of preceding emotional relationship, age of coital partners, environment where first intercourse took place, motivation of probands, difficulties during first intercourse, contraception used, frequency of sexual intercourse during period following first coitus. PMID- 8004373 TI - [Leukocyte adherence in women with ovarian carcinoma]. AB - Dynamic follow-up of cell-mediated immunity in women with malignant neoplasms of the ovary provides more valuable information on the course of the disease than a single value. The properties of leukocytes in patients with malignant ovarian tumours must be followed up on a longitudinal basis, as a signal of an approaching relapse of the disease is apparent sooner than its clinical manifestations. It appears that changes of biophysical mechanisms participate not only in the course of malignant ovarian disease but perhaps also in its genesis. PMID- 8004374 TI - [Correlation of clinical and virologic diagnosis of cervical infection with human papillomaviruses]. AB - The presented investigation is concerned with contemporary diagnostic possibilities of HPV Infection of the Cervix. The authors present the results of virological examinations of 228 female patients in the Centre for Oncological Prevention. The examination was made by hybridization techniques, using probes specific for HPV 6, 11, 16 and 18 and by serological methods where IgG antibodies were assessed against synthetic peptides, corresponding to several HPV epitopes, as antigens. 156 women (68.4%) were virologically positive, 72 (31.6%) were negative. Subsequently the authors investigated the diagnostic accuracy of HPV changes of the cervix by clinical methods, i.e. colposcopy and cytology, as compared with virological methods. On colposcopic examination uncertain--i.e. insignificant--results were recorded in 24.6%, on cytological examination in 19.7%. In patients where these methods gave unequivocal results (either + or-) a correct forecast of the presence of HPV during colposcopic examination was recorded in 71.1%, in cytological examinations in 66.9%. At least one of the clinical methods assessing papilloma virus infection was prognostically correct in 90.4%. From the investigation ensures that prebioptic methods provide the clinician with relatively reliable information on the presence of HPV infection and enable him to select a therapeutic and dispensarization procedure adequate to the finding. However, they cannot replace virological examination among other reasons also because they cannot assess the HPV type. PMID- 8004375 TI - [Ligation of the internal pelvic artery and its role in control of gynecologic hemorrhage]. PMID- 8004376 TI - [Infectious complications of IUDs]. PMID- 8004377 TI - [Conization of the uterine cervix using Histoacryl, a bioglue]. PMID- 8004378 TI - [Cholinesterases in amniotic fluid as biological markers of congenital neural tube defects]. PMID- 8004379 TI - [New aspects in the etiopathogenesis of hirsutism and polycystic ovary syndrome]. PMID- 8004380 TI - [Follicular stimulation and ovarian carcinoma]. PMID- 8004381 TI - [The concept of gynecology and obstetrics as a profession]. PMID- 8004382 TI - Separation and characterization of a novel isoenzyme of cyclic nucleotide phosphodiesterase from rat cerebrum. AB - Anion-exchange chromatography on a Mono-Q column of the supernatant fraction, after ultracentrifugation, from a homogenate of rat cerebrum, prepared under isotonic conditions in the presence of protease inhibitors, yielded a novel isoenzyme of cyclic nucleotide phosphodiesterase (PDE) with properties unlike those of known PDEs. The isoenzyme was insensitive to stimulation by Ca2+/calmodulin and cyclic GMP, and it hydrolyzed both cyclic AMP and cyclic GMP with KM values of 0.109 +/- 0.008 microM and 1.78 +/- 0.04 microM, respectively. The ratio of Vmax of hydrolysis of cyclic GMP to that of cyclic AMP was 1.90 +/- 0.07. Nicardipine (PDE I inhibitor), SK&F 94120 (PDE III inhibitor), rolipram (PDE IV inhibitor) and zaprinast (PDE V inhibitor) had very weak inhibitory effects on the PDE activity of the isoenzyme. These results suggest that the isoenzyme is a novel and previously unreported species of PDE, which we tentatively designate PDE VIII. PMID- 8004383 TI - Pharmacokinetics, plasma protein binding and urinary excretion of N omega-nitro-L arginine in rats. AB - The in vivo disposition of N omega-nitro-L-arginine (L-NOARG) has been examined in rats. Plasma concentrations of L-NOARG following an intravenous dose of 10 mg kg-1 were determined by high-performance liquid chromatography. Plasma L-NOARG concentrations declined biexponentially, with average half-lives of 11 min and 20 h. L-NOARG clearance did not appear to exhibit concentration-dependency below a plasma concentration of 4.56 x 10(-4) M (100 mg l-1). Ultrafiltration studies revealed insignificant binding of L-NOARG to rat plasma proteins. Urinary excretion of unchanged L-NOARG was minimal. These pharmacokinetic information may be useful in the design of in vivo experiments involving L-NOARG, as well as in the interpretation of the pharmacodynamics of this important nitric oxide synthase inhibitor. PMID- 8004384 TI - Blockade of nicotinic receptor-mediated release of dopamine from striatal synaptosomes by chlorisondamine and other nicotinic antagonists administered in vitro. AB - 1. Central nicotinic receptor function examined in vitro, by measuring nicotine induced [3H]-dopamine release from rat striatal synaptosomes. 2. The agonists (-) nicotine, acetylcholine, 1,1-dimethyl-4-phenylpiperazinium (DMPP) and cytisine (10(-7)-10(-4) M) all increased [3H]-dopamine release in a concentration dependent manner. Cytisine did not produce a full agonist response, compared to the other agonists. 3. The actions of nicotine, acetylcholine and cytisine were largely dependent on external Ca2+. In contrast, DMPP (10(-5) and 10(-4) M) evoked a marked release of [3H]-dopamine even in the absence of Ca2+. Nevertheless, in the presence of external Ca2+, responses to DMPP were completely blocked by the nicotinic antagonists chlorisondamine and mecamylamine (5 x 10(-5) M); in the absence of external Ca2+, blockade was only partial. 4. Chlorisondamine, mecamylamine and dihydro-beta-erythroidine (10(-8)-10(-4) M) produced a concentration-dependent block of responses to nicotine (10(-6) M). Approximate IC50 values were 1.6, 0.3 and 0.2 x 10(-6), respectively. Chlorisondamine and mecamylamine blocked responses to nicotine (10(-7)-10(-4) M) insurmountably, whereas dihydro-beta-erythroidine behaved in a surmountable fashion. 5. The occurrence of use-dependent block was tested by briefly pre exposing the synaptosomes to nicotine during superfusion with antagonist, and determining the response to a subsequent nicotine application. Consistent with a possible channel blocking action, brief pre-exposure to agonist increased the antagonist potency of chlorisondamine (approximately 25 fold). No significant use dependent block was detected with dihydro-beta-erythroidine. PMID- 8004385 TI - Blockade of nicotinic receptor-mediated release of dopamine from striatal synaptosomes by chlorisondamine administered in vivo. AB - 1. The chronic nicotinic blockade produced following in vivo administration of chlorisondamine was investigated in vitro. Nicotine-induced [3H]-dopamine release from striatal synaptosomes was used as a measure of central nicotinic receptor function. 2. In synaptosomal preparations from rats pretreated with a single administration of chlorisondamine (10 mg kg-1, s.c.), 1, 7, 21, 42, 63 or 84 days before they were killed, responses to (-)-nicotine (10(-6) M) were blocked. 3. In vivo administration of chlorisondamine (10 mg kg-1, s.c.), 7 days before rats were killed, produced a nicotinic blockade in vitro that was insurmountable even with a high concentration of (-)-nicotine (10(-4) M). 4. Both in vitro and in vivo administration of chlorisondamine blocked nicotinic responses to acetylcholine (10(-4) M). In contrast, neither in vitro nor in vivo administration of chlorisondamine reduced [3H]-dopamine release induced by high K+ (20 x 10(-3) M) or (+)-amphetamine (10(-6) M). 5. Nicotinic blockade resulting from in vitro administration of chlorisondamine (10(-5) M) recovered partially after 60 min wash-out, and completely by 90 min. In contrast, no recovery was seen in synaptosomes prepared from rats pretreated with chlorisondamine (10 mg kg 1, s.c.) in vivo. 6. Thus, in vivo treatment with chlorisondamine results in a quasi-irreversible, insurmountable block of CNS nicotinic receptors. The persistence of this block ex vivo indicates that physical trapping by the blood brain barrier is not solely responsible for the persistent blockade seen in vivo. The resistance of this blockade to prolonged in vitro wash-out suggests that the underlying mechanism differs from that associated with in vitro administration. PMID- 8004386 TI - Nitric oxide-dependent release of vasodilator quantities of calcitonin gene related peptide from capsaicin-sensitive nerves in rabbit skin. AB - 1. Calcitonin gene-related peptide (CGRP) is a potent and long lasting vasodilator in the cutaneous microvasculature of many species including the rabbit. In this study we have investigated the role of nitric oxide in the release of endogenous CGRP, in response to capsaicin, in rabbit skin. 2. Cutaneous blood flow was measured in response to intradermally-injected agents by a multiple site 133Xenon clearance technique. 3. The increased blood flow induced by capsaicin (100 nmol/site) and CGRP (3 pmol/site) was totally inhibited by the CGRP antagonist CGRP(8-37) (1 nmol/site), whilst the increased blood flow induced by sodium nitroprusside (0.3, 1 and 3 nmol/site) was unaffected by CGRP(8-37). 4. The nitric oxide synthase inhibitor NG-nitro-L-arginine methyl ester (L-NAME, 30 nmol/site) had no effect on the vasodilator response induced by CGRP, but significantly inhibited capsaicin-induced blood flow. The inhibitory effect of L NAME on capsaicin-induced blood flow was reversed by intradermal L-arginine (300 nmol/site), whilst the inactive enantiomer D-NAME (30 nmol/site) and the alpha adrenoceptor agonist phenylephrine (10 pmol/site), at a dose which had a similar effect to L-NAME on basal blood flow, had no effect on capsaicin-induced blood flow. 5. These results suggest that CGRP is the important vasodilator which is released from capsaicin-sensitive sensory nerves in rabbit skin and that the release of CGRP, but not its mechanism of vasodilator action, is nitric oxide dependent in the rabbit cutaneous microvasculature. PMID- 8004387 TI - Induction of emesis in Suncus murinus by pyrogallol, a generator of free radicals. AB - 1. We investigated whether or not pyrogallol, a generator of free radicals, is emetogenic in Suncus murinus, the house musk shrew. Pyrogallol (i.p.) caused dose dependent emesis in suncus with an ED50 value of 77.3 mg kg-1. At a dose of 128 mg kg-1, all suncus vomited with mean latency of 18.8 +/- 5.2 min and the number of vomiting episodes was 8.6 +/- 2.9. 2. The prophylactic effects of N-(2 mercaptopropionyl)-glycine (MPG), an antioxidant, and tropisetron, a 5 hydroxytryptamine3 (5-HT3) receptor antagonist, were studied. Pyrogallol (128 mg kg-1, i.p.)-induced emesis was prevented by treatment with MPG (i.p.) or tropisetron (s.c.) with ID50 values of 149 mg kg-1 and 117 micrograms kg-1, respectively. 3. Pyrogallol-induced emesis was completely prevented by surgical abdominal vagotomy. 4. The present results indicate that pyrogallol-induced emesis is characteristically very similar to that caused by cisplatin and support the idea that generation of free radicals causes the release of peripheral 5-HT, which stimulates vagal afferent sensory nerves to cause emesis. PMID- 8004388 TI - An endothelium-dependent contraction in canine mesenteric artery caused by caffeine. AB - 1. We examined whether or not caffeine caused an endothelium-dependent contraction (EDC) in canine mesenteric artery and whether the endothelium dependent contracting factors (EDCF) were arachidonic acid metabolites. 2. Caffeine (1, 3 and 10 mM) caused a transient contraction in endothelium-intact arterial strips. Removal of the endothelium significantly attenuated the caffeine (1 and 3 mM)-induced contraction. 3. Caffeine (1 mM)-induced EDC was not affected by quinacrine and manoalide (phospholipase A2 inhibitors), indomethacin and aspirin (cyclo-oxygenase inhibitors), ONO-3078 and S-1452 (thromboxane A2 antagonists) or AA-861 and TMK-777 (lipoxygenase inhibitors). 4. Caffeine (1 mM) induced EDC was also unaffected by 50-235 (an endothelin A receptor antagonist). In addition, catalase combined treatment with superoxide dismutase, or allopurinol (antioxidant) did not affect the EDC. 5. Gro-PIP and NCDC (phospholipase C inhibitors) did not affect the caffeine-induced EDC. However, wortmannin (a phospholipase D inhibitor) and staurosporine (a protein kinase C inhibitor) attenuated the caffeine-induced EDC. 6. The present experiments demonstrate that caffeine causes an EDC in canine mesenteric artery and suggest that the EDCF mediating this response is probably not arachidonic acid metabolites, endothelin or superoxide. Instead, caffeine-induced EDC may be due to activation of the phospholipase D pathway. PMID- 8004389 TI - Comparison of the effects of caffeine and other methylxanthines on [Ca2+]i in rat ventricular myocytes. AB - 1. The effects of caffeine and other methylxanthines were investigated on intracellular calcium concentration ([Ca2+]i) and contraction in rat isolated ventricular myocytes. The use of the fluorescent indicator, Indo-1, allowed simultaneous measurement of [Ca2+]i and the intracellular concentration of the methylxanthines. 2. Rapid application of caffeine (10 mM) produced a transient rise of [Ca2+]i which decayed to resting levels. This was accompanied by a transient contraction which decayed to a level above baseline. The addition of theophylline also produced a transient increase of [Ca2+]i. However, following the initial transient, contraction decayed before redeveloping to a maintained level. 3. Direct measurements showed that [caffeine]i rose more quickly than did [theophylline]i. The slower rise of [theophylline]i was associated with a delay in the increase of [Ca2+]i. At lower concentrations of the methylxanthines, theophylline was less effective than caffeine at initiating Ca release. The rate of entry of theobromine was similar to that of theophylline. 4. Isocaffeine did not produce a rise of [Ca2+]i. The rate of rise of [isocaffeine]i was much slower than that of either caffeine or theophylline. 5. Measurements of the oil:water partition coefficient showed that the order of relative partitioning into oil was: caffeine > theophylline > theobromine > isocaffeine. This is similar to the order of rate of entry into the cell. 6. We conclude that many of the differences in the effects of these methylxanthines can be attributed to differences in membrane permeability due to differences in oil:water partition. PMID- 8004390 TI - Induction of Na+/K(+)-ATPase activity by long-term stimulation of nicotinic acetylcholine receptors in C2C12 myotubes. AB - 1. To investigate the role of long-term stimulation of nicotinic acetylcholine receptors (AChRs) on the regulation of membrane potential, non-contracting C2C12 myotubes were stimulated for 1-4 days with carbachol (10 microM) and membrane potentials were measured by the intracellular microelectrode technique after washing out of the drug. 2. The membrane potential (-45.7 mV) gradually increased by 10.1 mV to -55.8 mV during 4 days treatment, which was caused by enhanced electrogenic Na+/K(+)-pumping. 3. The concentration-dependent enhancement of Na+/K(+)-ATPase activity in long-term carbachol-treated myotubes (4 days, EC50 = 5.3 microM) was prevented by co-treatment with the competitive nicotinic AChR antagonist, pancuronium but not by the muscarinic antagonist, atropine. 4. Enhanced Na+/K(+)-ATPase activity still developed in carbachol-stimulated myotubes during co-treatment (4 days) with the nicotinic AChR-channel blocker, chlorpromazine (1 microM). Membrane depolarization as such, obtained by incubation in high K+ medium (40 mM, 4 days) did not enhance Na+/K(+)-ATPase activity. 5. Non-treated myotubes possessed a high-affinity ouabain binding site (Kd = 119 nM) in association with the low Na+/K(+)-pumping activity. Long-term stimulation of myotubes (4 days) with carbachol or with a combination of carbachol and chlorpromazine was accompanied by the development of an additional low-affinity ouabain binding site (Kd = 13 microM). 6. Binding of monoclonal antibodies directed against either alpha 1- or alpha 2-subunit of Na+/K(+)-ATPase were both increased in myotubes treated with carbachol (4 days). 7. These results support the concept that nicotinic AChRs regulate Na+/K(+)-ATPase activity, independent of the functionality of the receptor-operated ion-channel. PMID- 8004391 TI - Alpha 1-adrenoceptors in the conduction system of rat hearts. AB - 1. We have characterized alpha 1-adrenoceptor in the conduction systems of the rat heart by quantitative autoradiography. 2. Consecutive 20 micron thick sections from a single rat heart containing the sinoatrial (SA) node and atrioventricular (AV) node were incubated with increasing concentrations of [3H] prazosin with or without 10 microM phentolamine. After exposure to 3H-Ultrofilm, optical densities corresponding to the SA node and AV node were determined by computerized densitometry after comparison with 3H standards. 3. The SA node and AV node were stained heavily for cholinesterase and they contained a higher concentration of alpha 1-adrenoceptors than the adjacent myocardium without a significant change in the affinity. 4. These results support the hypothesis that alpha 1-adrenoceptors may play an important role not only in inotropism but also in chronotropism of rat hearts. PMID- 8004392 TI - Involvement of ETA receptors in the facilitation by endothelin-1 of non adrenergic non-cholinergic transmission in the rat urinary bladder. AB - 1. Endothelin-1 (ET-1; 3-10 nM) raised the tone of rat bladders bathed in buffer containing atropine (1 microM) plus guanethidine (3.4 microM). In addition, ET-1 potentiated, in a concentration-dependent fashion (1-10 nM), the contractions evoked by both transmural nerve stimulation and applications of exogenous adenosine 5'-triphosphate (ATP). 2. The threshold concentration of ET-1 required to facilitate non-adrenergic non-cholinergic (NANC) transmission and potentiate ATP-induced contractions, was about 10 fold lower than that required to increase the bladder tone (3 nM). 3. The ET-1-induced increase in basal tension reached its maximal effect within 60-90 s. In contrast, the 7.8 microM ATP-induced contractions increased by 50% within the first minute following incubation with 10 nM ET-1 but required about 5 min to develop the maximal effect. 4. The ET-1 induced potentiation of NANC or ATP responses was long-lasting and persisted in spite of extensive washing. The recovery of the bladder excitability depended on the concentration of ET-1. Following the application of 3 nM ET-1, recovery required 30 min; applications of 10 nM ET-1 required at least 60 min for full recovery. 5. The ET-1-induced potentiation of responses was selective for ATP and related structural analogues. ET-1 did not modify the contractions induced by acetylcholine, 5-hydroxytryptamine, prostaglandin F2 alpha or bradykinin. 6. The potency of ET-2 was similar to that of ET-1. ET-3 and ET-C-terminal hexapeptide were inactive up to 100 M. Sarafotoxin S6b was 2 to 3 fold less potent than ET-1 whereas sarafotoxin S6c (100 nM) was inactive. AGETB-9 and AGETB-89, two ETB receptor agonists, were also inactive (up to 100 nM). 7. Removal of one or both disulphide bonds in ET-1 and tryptophan-21 formylation of ET-1, resulted in inactive peptides (up to 100 nM). 8. The ET-1 receptor antagonists, BE-18257B and FR 139317, blocked both the ET-1-induced rise in tone and the potentiation of ATP responses in a concentration-dependent fashion. FR 139317 was at least 30 fold more potent than BE-18257B. Both antagonists blocked at lower concentrations the ET-1 increase in bladder tone as compared to the ATP potentiation. The antagonism was slowly reversible. 9. Results are consistent with the presence of ETA receptors in the rat bladder, which mediate both actions of ET-1. The interaction of ET-1 with purinergic mechanisms is discussed. PMID- 8004393 TI - Fluspirilene block of N-type calcium current in NGF-differentiated PC12 cells. AB - 1. High voltage-activated calcium currents were recorded in nerve growth factor (NGF)-differentiated PC12 cells with the whole-cell patch clamp technique. After exposure to NGF for 3-10 days the PC12 cells developed neurone-like processes and calcium currents which were pharmacologically separable into L- and N-types (defined by sensitivity to nifedipine and omega-conotoxin GVIA respectively). 2. After blocking the L-type calcium channels with nifedipine (10 microM), omega conotoxin GVIA blocked approximately 85% of the remaining calcium current with an IC50 of 3 nM and a Hill coefficient of 1. The block by conotoxin GVIA was irreversible on the time scale of these experiments. These results suggested that the majority of the nifedipine-insensitive calcium current was N-type. 3. Fluspirilene, a substituted diphenylbutylpiperidine with potent neuroleptic properties, reversibly inhibited the N-type component in a dose-dependent manner with an IC50 of 30 nM. The Hill coefficient of the block was 0.25. The fraction of current blocked was the same at all test potentials examined (-30 to +40 mV). 4. These data indicate that the neuroleptic properties of fluspirilene may be due, at least in part, to an inhibition of neuronal N-type calcium channels. This finding raises the possibility that modulation of N-type calcium channel activity by drugs derived from substituted diphenylbutylpiperidines may provide a novel way of altering neurotransmitter release and hence brain function. PMID- 8004394 TI - Relationship between cytosolic calcium concentration and force in the papaverine induced relaxation of medial strips of pig coronary artery. AB - 1. The mechanisms of vasorelaxation induced by papaverine were investigated using front-surface fluorometry and fura-2-loaded medial strips of the pig coronary artery. 2. In the presence of extracellular Ca2+ (1.25 x 10(-3) M), histamine (10(-4) M) induced abrupt elevations of cytosolic calcium concentration, [Ca2+]i reaching a peak within 12 s (the first phase); after making a slight shoulder, [Ca2+]i declined gradually to reach sustained levels (the second phase). Force rapidly rose to reach maximum levels in 3 min, then gradually declined. Papaverine (10(-7)-10(-5) M) inhibited both the first and the second phases of [Ca2+]i elevation and the development of force induced by histamine, in a concentration-dependent manner. 3. In the absence of extracellular Ca2+, histamine (10(-4) M) induced a transient increase in [Ca2+]i and force, both of which were inhibited in a concentration-dependent manner by papaverine (10(-7) 10(-5) M). When papaverine was washed out, a second application of 10(-4) M histamine also induced transient increases in [Ca2+]i and force. The smaller the first response, the greater was the second response. The total amount of [Ca2+]i released from intracellular stores by the first and second application of histamine in the presence of papaverine was smaller than in its absence, thereby indicating a reduction of Ca2+ in the histamine-sensitive store. However, while papaverine (10(-5) M) did not affect the transient increase in [Ca2+]i induced by 2 x 10(-2) M caffeine, contractions were inhibited. 4. For a given level of [Ca2+]i, the force developed with the cumulative application of histamine(10-7 M 10-1 M) was greater than that observed with the cumulative application of extracellular Ca2+(0-7.5 x 10-3 M) during high K+ depolarization. Papaverine (10 7 M-10-5M) suppressed, in a concentration-dependent manner, the increase in [Ca2+]i and the force induced by cumulative applications of both histamine and extracellular Ca2+ during high K+ depolarization. The [Ca2+]i-force curve obtained by depolarization with K+, but not that obtained during histamine application, was shifted to the right by papaverine. Diltiazem, 10-7 M, a concentration causing a similar degree of relaxation to 10-5 M papaverine, did not shift the [Ca2+]i-force curve obtained with high K+. Nitroglycerin (10-6 M)and isoprenaline (10-6 M) shifted the [Ca2+]i-force curve to the right to a greater extent than did 10-5 M papaverine.5. These findings suggest that papaverine relaxes medial strips of the porcine coronary artery by two mechanisms. The first is mainly due to a decrease in [Ca2+]i, not only through inhibiting Ca2+ influx through either voltage-dependent or receptor-operated Ca2+ channels, but also by inhibiting agonist induced intracellular Ca2+ release. This occurs presumably by interference with the signal transduction pathway for histamine and by a depletion of Ca2+ in histamine-sensitive stores. Secondly, the [Ca2+]i-sensitivity of certain contractile mechanisms may be minimally decreased. PMID- 8004395 TI - Inhibition by fatty acids of cyclic AMP-dependent protein kinase activity in brush border membranes isolated from human placental vesicles. AB - 1. The inhibitory effects of arachidonic acid (AA) and a number of structurally related fatty acids on cyclic AMP-dependent protein kinase activity have been investigated in brush border membranes (BBM) prepared from human placental vesicles. 2. BBM vesicles were characterized by electron microscopy and displayed enrichment of the appropriate marker enzymes, alkaline phosphatase and gamma glutamyltranspeptidase; BBM were prepared by vesicles lysis in hypotonic medium. 3. Cyclic AMP-dependent protein kinase (PKA) activity was measured in BBM. At 1 microM, cyclic AMP stimulated a 4.2 +/- 0.06 fold increase over basal levels of [32P]-phosphate incorporation into the synthetic substrate kemptide and this effect was abolished by a selective PKA inhibitor. By use of synergistic pairs of site-selective cyclic AMP analogues, the kinase was identified as the type II enzyme. 4. Cyclic AMP-stimulated PKA activity was inhibited by 10 microM AA and this effect was significantly enhanced by nordihydroguaiaretic acid (NDGA) + indomethacin (Indo), inhibitors of the lipoxygenase and cyclo-oxygenase pathways of AA metabolism respectively. 5. Oleic acid, elaidic acid, but not caprylic or palmitic acids, also significantly inhibited PKA activity and this effect was again enhanced by NDGA + Indo. While arachidonyl alcohol alone was not inhibitory, in the presence of the metabolic inhibitors a significant reduction in stimulated activity was observed. 6. The commercially available PKA type II holoenzyme (activated by cyclic AMP), but not the free catalytic subunit, was inhibitable by AA, oleic or elaidic acids. 7. These results suggest that PKA localized to the brush border membrane of human placental vesicles is inhibited by fatty acids which may compete with cyclic AMP for binding to the kinase regulatory subunit. The reported inhibition by fatty acids of cyclic AMP dependent Cl- secretion in epithelial cells may therefore be due in part to negative regulation of a Cl- channel-associated PKA. PMID- 8004397 TI - Importance of inositol (1,4,5)-trisphosphate, intracellular Ca2+ release and myofilament Ca2+ sensitization in 5-hydroxytryptamine-evoked contraction of rabbit mesenteric artery. AB - 1. Small strips from third-order branches of rabbit mesenteric artery (approximately 150-200 microM wide) contracted in response to noradrenaline (10 microM) or 5-hydroxytryptamine (5-HT; 10 microM) in oxygenated Krebs solution containing 2.5 mM Ca2+. In a Ca(2+)-free mock intracellular solution (0 Ca2+ plus 0.2 mM EGTA), noradrenaline (10 microM) and caffeine (10 mM) induced only a single, transient contraction in artery strips, while 5-HT (10 microM) failed to induce any response. 2. In strips of mesenteric artery which had been permeabilized with Staphylococcus alpha-toxin and bathed in Ca(2+)-free mock intracellular solution, noradrenaline (10 microM), caffeine (10 mM) and D-myo inositol (1,4,5)-trisphosphate (IP3, 100 microM), but not 5-HT (10 or 100 microM) induced a transient contraction. In contrast to the non-permeabilized strips, contractions to noradrenaline, caffeine and IP3 were restored by prior incubation (10 min) in solution containing 0.08 microM Ca2+. The contractions to noradrenaline and IP3 in permeabilized muscle strips required the presence of 100 microM guanosine 5'-triphosphate (GTP), although in the absence of Ca2+. GTP alone did not induce contraction. 3. Exposure of permeabilized mesenteric artery strips to IP3 significantly reduced the subsequent contractile responses to caffeine. Contractile responses to caffeine and IP3 were abolished by the Ca(2+) ATPase inhibitor, thapsigargin (1 microM). 4. Ca2+ (0.1-10 microM) induced concentration-dependent contraction in permeabilized artery strips. In strips which were submaximally contracted with 0.5 microM Ca2+/100 microM GTP, the subsequent addition of 5-HT (10 microM) stimulated further contraction. The protein kinase C inhibitor, H-7 (1 microM) abolished the 5-HT/GTP-induced contraction, but did not alter the contraction to Ca2+. 5. In non-permeabilized, endothelium-denuded segments of rabbit mesenteric artery bathed in Ca2+-replete Krebs solution, noradrenaline (10 microM) stimulated a rapid, transient accumulation of IP3. 5-HT(100 microM) failed to stimulate IP3 accumulation during exposure periods of up to 5 min. 5-HT (100 microM)did stimulate IP3 accumulation if the external K+ concentration was raised (to around 25 mM). This concentration of K+ alone did not stimulate IP3 production and the 5-HT-stimulated IP3 accumulation in the presence of elevated extracellular [K+] was abolished by the alpha l-adrenoceptor antagonist, prazosin(O.1 microM).6. These results suggest that intracellular Ca2+ release does not play an important role in 5-HT-induced smooth muscle contraction in the rabbit mesenteric artery. This is despite the fact that a significant intracellular Ca2+ pool is present in these cells, which can be discharged by either noradrenaline or IP3.However, 5-HT did stimulate smooth muscle contraction in the presence of raised intracellular calcium,suggesting that a component of the contraction to 5-HT will reflect an increase in myofilament Ca2+sensitivity, possibly due to the activation of protein kinase C. PMID- 8004396 TI - Evidence from receptor antagonists of an important role for ETB receptor-mediated vasoconstrictor effects of endothelin-1 in the rat kidney. AB - 1. To characterize the receptor subtype(s) mediating the renal vasoconstrictor effects of the endothelin (ET) and sarafotoxin (SX) peptides in the isolated perfused kidney of the rat, we have examined the effects of endothelin-1 (ET-1), sarafotoxin 6b (SX6b) and sarafotoxin 6c (SX6c) as agonists, BQ-123 and FR 139317 as selective ETA receptor antagonists, and PD 145065 as a non-selective (ETA and ETB) receptor antagonist. We have also compared in the anaesthetized rat the systemic pressor and renal vasoconstrictor effects of ET-1 and SX6c alone or after pretreatment with PD 145065. 2. In the isolated perfused kidney, ET-1, SX6b and SX6c all gave similar concentration-dependent increases in perfusion pressure. The ETA receptor selective antagonists, BQ-123 and FR 139317, both partially blocked the increase in perfusion pressure induced by ET-1. In contrast, PD 145065 completely blocked the increase in perfusion pressure caused by ET-1. 3. Indomethacin (10 microM) had no effect on the ET-1-induced increases in perfusion pressure but significantly reduced the vasoconstriction induced by low concentrations of SX6c, without affecting responses to high concentrations. In the anaesthetized rat, indomethacin (5 mg kg-1) did not modify the systemic pressor or renal vasoconstrictor effects of ET-1 or SX6c. 4. In anaesthetized rats, bolus intravenous injections of ET-1 or SX6c (0.1, 0.25, 0.5 or 1.0 nmol kg 1) produced initial transient depressor responses followed by sustained and dose dependent increases in mean arterial pressure (MAP). Both peptides caused an equipotent fall in renal blood flow (RBF).PD 145065 (5 mg kg-1) partially antagonized the systemic pressor effects of ET-1 and SX6c but completely blocked the fall in RBF and rise in renal vascular resistance (RVR) induced by ET-1 and SX6c. PD 145065 also antagonized the transient depressor effect following the bolus administration of either ET-1 or SX6c.5. These results indicate that ET/SX induced renal vasoconstriction is mediated via ETA and ETB-like receptors with ETB receptors having a predominant role in vivo. This may be of therapeutic relevance for an ETA receptor-selective antagonist may offer only limited protection against the deleterious renal effects of endogenous ETs. PMID- 8004399 TI - Inhibitory effects of nordihydroguaiaretic acid on ETA-receptor-mediated contractions to endothelin-1 in rat trachea. AB - 1. It has been shown previously that nordihydroguaiaretic acid (NDGA) inhibits endothelin-1 (ET-1)-induced contractions in rat isolated tracheal smooth muscle. To investigate the underlying mechanisms, this study examined the effects of NDGA on various aspects of the ETA and ETB receptor-effector systems which mediate ET 1-induced contractions in this preparation. 2. NDGA inhibited contractions induced by each of the isoforms of ET (ET-1, ET-2 and ET-3) but not those induced by the ETB receptor-selective agonist, sarafotoxin S6c, the cholinoceptor agonist, carbachol or the depolarizing spasmogen, KCl. 3. Quantitative autoradiographic studies of [125I]-ET-1 binding to rat tracheal smooth muscle indicated that NDGA was not an ET receptor antagonist. 4. NDGA inhibited the ETA receptor-mediated, intracellular Ca(2+)-dependent contractions induced by 100 nM ET-1 in Ca(2+)-free solution (by 75%, P < 0.01). Furthermore, NDGA markedly inhibited the contractions induced by ryanodine and cyclopiazonic acid; contractions purportedly due to Ca2+ release from intracellular stores. 5. Like NDGA, the sarcoplasmic reticulum Ca(2+)-ATPase inhibitors cyclopiazonic acid and thapsigargin inhibited contractions to ET-1, but not carbachol or KCl. However, cyclopiazonic acid, but not NDGA, also (a) induced transient contractions in rat trachea, (b) potentiated contractions induced by KCl, and (c) potentiated the extracellular Ca(2+)-dependent phase of ET-1-induced contractions, indicating that NDGA did not inhibit ET-1-induced contractions through Ca(2+)-ATPase inhibition and depletion of sarcoplasmic reticular Ca2+. 6. In control preparations, ET-1 induced a slowly developing, sustained contraction. However, in the presence of NDGA or the ETA receptor antagonist, BQ123, ET-1-induced contractions resembled the transient contractions induced by sarafotoxin S6c. In nominally Ca2+-free solution, ETA receptor mediated contractions induced by ET-1 developed very slowly and were inhibited by NDGA.7. Additional studies indicated that the inhibitory effects of NDGA on endothelin-1-induced contractions were not the result of any significant actions of NDGA on lipoxygenase, cytochrome P450, L orT-type Ca2+-channels, Na+-channels or protein kinase C.8. In summary, NDGA selectively inhibited ET-1-induced contractions in rat tracheal smooth muscle via a lipoxygenase-independent mechanism involving inhibition of the ETA but not the ETB, receptor effector system. NDGA did not appear to inhibit the initial events in the ETA signal transduction pathway, such as receptor binding and protein kinase C activation. However, NDGA inhibited the intracellular Ca2+-dependent component of ET-1-induced contraction, possibly by inhibiting mobilisation of intracellular Ca2+. As an apparent direct consequence of inhibiting the ETA receptor-effector system, NDGA markedly changed the time course of ET-1-induced contractions; from a slowly developing and sustained contraction into a transient contraction resembling that induced by sarafotoxin S6c. PMID- 8004398 TI - Increased arterial distensibility induced by the angiotensin-converting enzyme inhibitor, lisinopril, in normotensive rats. AB - 1. We investigated possible structural correlates of the beneficial effect of chronic angiotensin-converting enzyme inhibition (ACEI) with lisinopril on the aortic distensibility of normotensive rats. 2. Experiments were performed in young (4-month old), normotensive, Wistar rats which received lisinopril in their drinking water (0.9 or 9 mg kg-1 day-1) for 9 months. 3. Following ACEI treatment, rats were pithed and aortic pulse wave velocity was measured during the progressive rise in mean arterial blood pressure produced by i.v. infusion of the alpha 1-adrenoceptor agonist, phenylephrine. The slope of the regression line relating aortic pulse wave velocity to mean arterial blood pressure was taken as an index of aortic distensibility. Following this, the aorta was fixed in situ at a normotensive pressure level and histomorphometry was performed. We also measured the calcium content of the aortic wall by atomic absorption. 4. The lower dose of lisinopril failed to lower systolic arterial blood pressure (unanaesthetized rat) or mean arterial blood pressure (pithed rat). Chronic ACEI with the higher dose of lisinopril lowered both systolic arterial blood pressure (104 +/- 6 mmHg, controls 133 +/- 4 mmHg, unanaesthetized), and mean arterial blood pressure (27 +/- 1 mmHg, controls 34 +/- 2 mmHg, pithed). 5. Although the lower dose of lisinopril did not lower blood pressure, it did improve aortic distensibility as revealed by a fall in the slope relating aortic pulse wave velocity (Y) to mean arterial blood pressure (X). Values were 5.7 +/- 0.7, 3.8 +/ 0.6 and 2.7 +/- 0.3 in controls, and in low and high ACEI groups, respectively. 6. Lisinopril treatment did not modify the calcium content, the internal and external diameters or the medial thickness of the aorta. Chronic ACEI did, however, increase the thickness of the medial elastic fibres (controls 3.55 +/- 0.05 microm, low dose ACEI 4.05 +/- 0.15 gm (P<0.05), and high dose ACEI4.18 +/- 0.15 microm (P<0.05)).7. In conclusion, we would suggest that ACEI treatment with a low dose of lisinopril can decrease aortic stiffness via a pressure-independent mechanism which possibly involves an effect of ACEI on elastic fibres. PMID- 8004400 TI - Characterization of the tachykinin NK2 receptor in the human bronchus: influence of amastatin-sensitive metabolic pathways. AB - 1. The aim of this study was to characterize the tachykinin NK2 receptor subtype mediating the spasmogenic response in the human isolated bronchus. The motor response to neurokinin A (NKA) and the selective NK2 agonist [beta Ala8]NKA(4 10), as well as the antagonistic effects of cyclic (L659,877) and linear (MEN 10376) peptide NK2 antagonists were assessed in the presence or absence of amastatin (an inhibitor of aminopeptidases A and M). 2. NKA was more potent than [beta Ala8]NKA(4-10) in eliciting bronchoconstriction (pD2 being 7,43 and 6,87 respectively). In the presence of amastatin (1 microM), the estimated affinity of [beta Ala8]NKA(4-10), but not that of NKA, was significantly increased to yield a pD2 of 7,44. 3. L659,877 and MEN 10376 inhibited [beta Ala8]NKA(4-10)-induced contraction with similar affinities; pA2 values were 5.7 +/- 0.22 and 6.3 +/- 0.32, respectively. Amastatin (1 microM) increased the potency of MEN 10376 to 7.28 +/- 0.46, whereas that of L659,877 was unaffected. 4. In the presence of amastatin the pseudopeptide MDL 28,564 behaved as a partial agonist. 5. We conclude that the NK2 receptor subtype present in the human bronchus has properties similar to those described for the circular muscle of the human colon and thus may be classified as a 'NK2A' subtype. We show that the apparent potency of peptides, bearing N-terminal acidic residues, is influenced by an amastatin sensitive peptidase, possibly aminopeptidase A. PMID- 8004402 TI - Potentiation by tonic A2a-adenosine receptor activation of CGRP-facilitated [3H] ACh release from rat motor nerve endings. AB - 1. The effect of calcitonin gene-related peptide (CGRP) on [3H]-acetylcholine ([3H]-ACh) release from motor nerve endings and its interaction with presynaptic facilitatory A2a-adenosine and nicotinic acetylcholine receptors was studied on rat phrenic nerve-hemidiaphragm preparations loaded with [3H]-choline. 2. CGRP (100-400 nM) increased electrically evoked [3H]-ACh release from phrenic nerve endings in a concentration-dependent manner. 3. The magnitude of CGRP excitation increased with the increase of the stimulation pulse duration from 40 microseconds to 1 ms, keeping the frequency, the amplitude and the train length constants. With 1 ms pulses, the evoked [3H]-ACh release was more intense than with 40 microseconds pulse duration. 4. Both the nicotinic acetylcholine receptor agonist, 1,1-dimethyl-4-phenylpiperazinium, and the A2a adenosine receptor agonist, CGS 21680C, increased evoked [3H]-ACh release, but only CGS 21680C potentiated the facilitatory effect of CGRP. This potentiation was prevented by the A2a adenosine receptor antagonist, PD 115,199. 5. Adenosine deaminase prevented the excitatory effect of CGRP (400 nM) on [3H]-ACh release. This effect was reversed by the non-hydrolysable A2a-adenosine receptor agonist, CGS 21680C. 6. The nicotinic antagonist, tubocurarine, did not significantly change, whereas the A2-adenosine receptor antagonist, PD 115,199, blocked the CGRP facilitation. The A1-adenosine receptor antagonist, 1,3-dipropyl-8-cyclopentylxanthine, potentiated the CGRP excitatory effect. 7. The results suggest that the facilitatory effect of CGRP on evoked [3H]-ACh release from rat phrenic motor nerve endings depends on the presence of endogenous adenosine which tonically activates A2a-adenosine receptors. Since both CGRP and A2a-adenosine receptors are positively coupled to the adenylate cyclase/cyclic AMP system, cooperation between these receptors might occur at the second messenger transduction system level. PMID- 8004401 TI - Inhibition of human monocyte adhesion to endothelial cells by the coumarin derivative, cloricromene. AB - 1. The ability of the coumarin derivative cloricromene (8-monochloro-3-beta diethylaminoethyl-4-methyl-7-ethoxy- carbonylmethoxycoumarin) to inhibit monocyte adhesion to human cultured umbilical vein endothelial cells (HUVEC) was investigated. 2. Cloricromene (10-200 microM) inhibited, in a concentration dependent manner, the adhesion of both resting and activated monocytes to HUVEC. Significant inhibition was reached with drug concentrations ranging between 15 to 30 microM. 3. The inhibitory activity was, at least in large part, directed to monocytes since no inhibition was observed after selective preincubation of HUVEC with cloricromene and the drug maintained its effect also on monocyte adhesion to paraformaldehyde-treated HUVEC. 4. Inhibition was maximal after 1 min of exposure of monocytes to cloricromene and persisted even in the absence of the drug. 5. Both basal and chemoattractant-mediated monocyte adhesion was inhibited by cloricromene as it was by TS1/18, a monoclonal antibody (mAb) directed to beta 2 integrins; however, cytofluorimetric analysis showed that cloricromene was unable to modulate the expression of beta 2 integrins on the monocyte surface. 6. When monocyte adhesion was mediated by a large set of adhesive receptors, as obtained after treatment of HUVEC with either interleukin 1 beta (IL-1; 50 ng ml-1) or tumour necrosis factor-alpha (TNF; 100 u ml-1), the inhibitory effect of cloricromene was considerably reduced. 7. The results of this study show that cloricromene may regulate monocyte adhesion to HUVEC, an event relevant in vivo in the pathogenesis of inflammatory and atherosclerotic processes. PMID- 8004403 TI - Calcium-dependence of histamine- and carbachol-induced inositol phosphate formation in human U373 MG astrocytoma cells: comparison with HeLa cells and brain slices. AB - 1. Histamine (1 mM) induced an accumulation of inositol monophosphate ([3H]-IP1) in the U373 MG human astrocytoma cell line which increased with time in the presence of 30 mM Li+. After a 30 min incubation period with 1 mM histamine [3H] IP1 was the major product detected (84 +/- 1% of total [3H]-IPx) and was present at a level 11 (+/- 1) fold of basal accumulation. 2. Concentration-response curves for histamine-induced [3H]-IP1 accumulation in U373 MG cells (EC50 5.4 +/- 0.5 microM) were shifted to the right in a parallel fashion by mepyramine (slope of a Schild plot 0.99 +/- 0.08), yielding a Kd for mepyramine of 3.5 +/- 0.3 nM, consistent with the involvement of histamine H1-receptors. 3. The temelastine sensitive binding of [3H]-mepyramine to a membrane fraction from U373 MG cells was hyperbolic and had a mean Kd of 2.5 +/- 1.0 nM. The maximum amount of temelastine-sensitive binding was 86 +/- 19 pmol g-1 membrane protein. 4. Carbachol also induced [3H]-IP1 accumulation in U373 MG cells, 2.8 (+/- 0.1) fold of basal with 1 mM carbachol, with an EC50 of 48 +/- 8 microM. Pirenzepine shifted carbachol concentration-response curves to the right (slope of Schild plot 0.89 +/- 0.07) giving a Kd for pirenzepine of 0.10 +/- 0.01 microM, suggesting that phosphoinositide hydrolysis in U373 MG cells is mediated by the M3-, rather than the M1-, muscarinic receptor subtype. 5. [3H]-IP1 accumulation induced by both 1 mM histamine and by 1 mM carbachol increased when the Ca2+ concentration of the medium was increased from 'zero' (no added Ca2+) to 0.3 mM. Histamine-stimulated [3H]-IP1 accumulation was further increased, although not so markedly, as the Ca2+ was raised to 4 mM. The same pattern was apparent with histamine-induced accumulations of [3H]-IP2 and [3H]-IP3. In contrast, [3H]-IPx accumulation in response to carbachol increased between 0.3 and 1.3 mM, but thereafter remained unchanged ([3H]-IP1) or declined ([3H]-IP2 and [3H]-IP3). 6. In HeLa cells, [3H]-IP1 accumulations induced by 1 mM histamine and 1 mM carbachol showed the same pattern of Ca2+ dependence and were independent of extracellular Ca2+ above 0.3 mM (histamine) or 1.3 mM (carbachol). The response to carbachol appeared to be mediated by an M3-muscarinic receptor (apparent Kd for pirenzepine 0.09 microM). 7. In cross-chopped slices of guinea-pig cerebral cortex and guinea-pig cerebellum, [3H]-IPI accumulation induced by 1 mM histamine in the presence of 10 mM Li+ increased as the extracellular Ca2+ was increased from 0.3 to 2.5 mM, but a further increase to 4 mM had no further effect. In contrast the response to histamine in rat cerebral cortex increased markedly between 1.3 and 4 mM Ca2+. Accumulations of [3H]-IP1 induced by carbachol in guinea-pig or rat cerebral cortical slices were not increased as extracellular Ca2+ was raised from 0.3 to 4 mM.8. Nimodipine (100 nM) and w-conotoxin (3 microM) had no significant effect on histamine-induced [3H]-IP1accumulation in rat cerebral cortical slices or in U373 MG cells. 9. We conclude that histamine induced [3H]-IP1 accumulation in U373 MG cells does appear to have a component dependent on the extracellular Ca2+ concentration. The degree of Ca2+-dependence approaches that observed in guinea-pig cerebral cortex but is much less than in rat cerebral cortex.Whether U373 MG cells will be of use as a model system for the apparent Ca2+-entry component observed in guinea-pig or rat brain slices remains to be established. PMID- 8004404 TI - Endothelin receptors mediating functional responses in human small arteries and veins. AB - 1. In the present study, responses of human omental small arteries and veins to endothelin-1 and endothelin-3 were characterized by use of the ETB receptor selective agonist, sarafotoxin S6c, the ETA receptor antagonist, BQ123, the ETB receptor antagonist, IRL1038, the NO-synthase inhibitor NG-monomethyl-L-arginine (L-NMMA, 300 microM) and indomethacin (10 microM). 2. Small arteries (internal diameter 413 +/- 22 microns) and parallel running veins (646 +/- 35 microns) were mounted in a myograph under a normalized tension equivalent to 90% of a transmural pressure of 100 mmHg and 19 mmHg in vivo, respectively. 3. In small arteries and veins, endothelin-1 caused a concentration-dependent increase in wall tension (Emax = 3.90 +/- 0.56 mN mm-1 and 1.90 m +/- 0.32 mN mm-1 respectively, P < 0.05) and was equipotent (arteries: pD2 = 8.91 +/- 0.11; veins: pD2 = 8.63 +/- 0.08, NS). In endothelium intact arteries, L-NMMA significantly enhanced the sensitivity to endothelin-1 (pD2 control: 8.92 +/- 0.16; pD2 L-NMMA: 9.37 +/- 0.11; P < 0.05). L-NMMA did not affect the sensitivity of veins to endothelin-1. Indomethacin was without effect in arteries and veins. In veins, endothelin-3 was about a hundred times less potent than endothelin-1 and showed a biphasic response curve. Small arteries did not contract to endothelin-3. Neither small arteries nor veins contracted to sarafotoxin S6c. Furthermore, no relaxation to endothelin-1 or sarafotoxin S6c was seen in any precontracted vessels. 4. BQ123 (0.03-3 MicroM) produced a concentration-dependent rightward parallel displacement of the endothelin-l concentration-response curve in small arteries and veins yielding pA2 values of 7.09 and 7.48 respectively. The slope of the Schild plot in arteries and veins was 1.26 +/- 0.24 (NS from unity) and 0.61 +/- 0.13 (P <0.05 compared to unity) respectively. IRL1038 (3 MicroM) did not affect the potency of endothelin-1 in arteries and veins. In veins, the low sensitivity component (pD2 = 7.16 +/- 0.08) of the biphasic response curve to endothelin-3 was completely blocked by BQ123 (3 MicroM), whereas the high sensitivity component (pD2 = 8.66 +/- 0.08) was resistant to BQ123 (3 MicroM) and IRL1038 (3 MicroM).5. These results indicate that contractions of human small vessels to endothelin-l are predominantly mediated by ETA receptors and that nitric oxide modulates the response to endothelin-l in small arteries but not in veins. The different antagonistic potency of BQ123 against endothelin-l and the differential endothelin-1/endothelin-3 potency ratios in arteries and veins provide evidence for the hypothesis that ETA receptors in human small arteries are different from ETA receptors in human small veins. There is no evidence of contractions mediated by 'classical' ETB receptors in these vessels, but small veins appear to contain a functional non ETA/non ETB receptor with a high affinity for endothelin-3. PMID- 8004405 TI - Comparison of the effects of IVth ventricular administration of some tryptamine analogues with those of 8-OH-DPAT on autonomic outflow in the anaesthetized cat. AB - 1 The present study compares the effects on representative autonomic outflows of IVth ventricular application of tryptamine analogues which act at 5-HT1 receptors with 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT). 2 Cumulative doses of 8 OH-DPAT, N,N-di-n-propyl-5-carboxamidotryptamine (DP-5-CT) and 5 carboxamidotryptamine (5-CT, 2.5-40 nmol kg-1), sumatriptan (10-160 nmol kg-1), indorenate (100-800 nmol kg-1), 5-hydroxytryptamine (5-HT, 20-640 nmol kg-1) both alone and in the presence of cinanserin (0.1 mg kg-1) were given into the IVth ventricle of cats which were anaesthetized with a mixture of alpha-chloralose and pentobarbitone sodium, neuromuscularly blocked and artificially ventilated. Recordings were made of arterial blood pressure, heart rate, renal, cardiac, splanchnic and phrenic nerve activities, femoral arterial flow, tracheal and intragastric pressures. 3 Central application of each of the agonists evoked significant falls in arterial blood pressure. In addition 8-OH-DPAT, DP-5-CT, 5 CT and 5-HT all evoked a differential inhibition of sympathetic nerve activities, with renal nerve activity being the most sensitive and cardiac nerve activity the least sensitive. In the dose-ranges used, administration of sumatriptan evoked reductions only in renal and splanchnic nerve activities whilst indorenate reduced activity in all three sympathetic nerves to a similar extent. 4. The effect of the agonists on heart rate was more inconsistent than the effects on sympathetic outflow.IVth ventricular application of 5-CT and sumatriptan were without effect on heart rate whilst 8-OH-DPAT, DP-5-CT, indorenate and 5-HT alone and in the presence of cinanserin all evoked significant bradycardias. However, whilst atropine partially reversed the bradycardias evoked by 8-OHDPAT and only slightly reversed those caused by indorenate, atropine was without effect on those evoked by DP-5-CT or 5-HT.5. None of the analogues tested had significant effects on gut motility, phrenic nerve discharge or tracheal pressure. 8-OH-DPAT, DP-5-CT, indorenate and 5-HT were without effect on femoral arterial conductance. However, following pretreatment with cinanserin, 5-HT evoked a significant reduction in femoral arterial conductance. At its highest dose, sumatriptan evoked a significant increase in femoral arterial conductance as did 5-CT at the 20 nmol kg-1 dose.6. It is concluded that the present data support the view that 5-HT1A receptors at the level of the brainstem are involved in the central sympathoinhibitory effects caused by intravenous administration of 5-HT1A agonists. Further, brainstem 5-HT1A receptors play an important role in the control of renal sympathetic outflow while brainstem 5-HT2 receptors are involved in the control of skeletal muscle and/or skin blood flow. Selective tryptamine agonists for 5-HT1A receptors differ from non-tryptamine agonists in that they do not cause an increase in central cardiac vagal tone. PMID- 8004408 TI - Behavioral research. PMID- 8004409 TI - The NCIC/CCS behavioral initiative. National Cancer Institute of Canada Canadian Cancer Society. AB - The NCIC's behavioral initiative is comprised of three pillars, each of which is designed to make an important independent contribution toward a reduction in cancer incidence, morbidity or mortality rates. It is also expected that the activities in one area will complement those in the other areas, thereby creating a synergistic effect. To determine if the objectives of the Centre for Behavioral Research and Program Evaluation (CBRPE) are being met, the NCIC has committed to an ongoing assessment of the CBRPE's performance, including an independent review of its scientific merit by a site visit conducted at the end of the second year of the CBRPE's operation. Thus, while the behavioral initiative represents a different type of investment by the NCIC, its contributions will be judged via a process that is central to all NCIC activities--the assessment of scientific merit by teams of persons recognized nationally and internationally for their expertise in social and behavioral research as it pertains to cancer. PMID- 8004407 TI - Mg(2+)-dependent inhibition of KATP by sulphonylureas in CRI-G1 insulin-secreting cells. AB - 1 Patch-clamp recording techniques were used to examine the effects of tolbutamide, glibenclamide, meglitinide and thiopentone on KATP in CRI-GI insulin secreting cells in the presence and absence of Mg2+. 2 In the absence of Mg2+ in the intracellular bathing solution, tolbutamide was significantly less effective when applied either to the intracellular or to the extracellular surfaces of cell free patches. Removal of extracellular Mg2+ did not alter the effectiveness of tolbutamide provided that Mg2+ was present at the intracellular surface of the patch. 3 Tolbutamide was also significantly less effective when applied to the intracellular surface of cell-free patches when Mn2+ was used as a replacement for Mg2+. 4 Both the sulphonylurea, glibenclamide and the non-sulphonylurea derivative, meglitinide also showed Mg2+ dependent inhibitory effects in cell free patches. In contrast, the barbiturate thiopentone inhibited KATP in a Mg(2+) independent manner. 5 Whole-cell IK(ATP) were used to quantify the effects of tolbutamide and glibenclamide in the presence and absence of intracellular Mg2+. Concentration-inhibition curves, in the presence of intracellular Mg2+, resulted in IC50 values of 12.1 microM and 2.1 nM for tolbutamide and glibenclamide, respectively. In the absence of intracellular Mg2+, the corresponding IC50 values were 25.3 mM and 3.6 microM, respectively. The values of IC50 for thiopentone in the presence and absence of intracellular Mg2+ were 69.4 microM and 69.2 microM, respectively. 6 With respect to the high affinity binding sites for [3H] glibenclamide in CRI-G1 membranes, no significant differences were found between the dissociation constants for, or the maximal binding capacities of, [3H] glibenclamide in the presence or absence of Mg2+. 7. In the CRI-G1 insulin secreting cell line, it is concluded that intracellular Mg2+ does not influence the affinity of the sulphonylureas for the sulphonylurea receptor but that this ion is critically important for the interaction between the sulphonylurea receptor and KATP. PMID- 8004410 TI - Molecular genetics of Wilms' tumor: insights into normal and abnormal renal development. AB - Wilms' tumor is a pediatric malignancy of the kidney. Studies of the genetics of this disease have revealed a limited number of genes implicated in tumor initiation. The identification and characterization of these genes and their products represents an immediate challenge to further our understanding of the molecular events involved in tumor progression. Understanding the events leading to deregulation of cell growth and proliferation in Wilms' tumor has lead to the ability to predict a group of individuals at risk for this malignancy. PMID- 8004411 TI - Guideline on control of computerized systems in drug manufacturing. Parenteral Drug Association. PMID- 8004406 TI - Effects of cyclic AMP and analogues on neurogenic transmission in the rat tail artery. AB - 1 The effects of two 8-substituted analogues of adenosine 3':5'-cyclic monophosphate (cyclic AMP) were compared with those of forskolin and isoprenaline on [3H]-noradrenaline release and vasoconstriction induced by electrical field stimulation (24 pulses at 0.4 Hz, 200 mA, 0.3 ms duration) in the rat tail artery, in the absence and in the presence of protein kinase inhibitors. 2 8 Bromo-adenosine 3':5'-cyclic monophosphate (8-bromo-cyclic AMP, 10-300 microM), 8 (4-chlorophenyl-thio)-adenosine 3':5' cyclic monophosphate (8-pCPT-cyclic AMP, 3 300 microM), forskolin (0.3-10 microM) and isoprenaline (1 nM-1 microM) all concentration-dependently enhanced stimulation-induced [3H]-noradrenaline release. The effect of cyclic AMP analogues was larger (2.5 fold at 300 microM) than those of cyclic AMP elevating drugs (1.6 fold at 10 microM for forskolin and 1.5 fold at 30 nM for isoprenaline). 3 At concentrations active at the prejunctional level, the four drugs had differential effects on stimulation induced vasoconstriction, which was enhanced by the two cyclic AMP analogues, decreased by forskolin and not significantly altered by isoprenaline. 4 The [3H] noradrenaline release-enhancing effects of 8-bromo-cyclic AMP, forskolin and isoprenaline were significantly decreased by the cyclic AMP-dependent protein kinase (PKA) inhibitor (N-[2-((3-(4-bromophenyl)-2-propenyl)-amino)-ethyl]-5- isoquinolinesulphonamide, di-hydrochloride) (H-89; 100 nM). By contrast they were unaffected by the cyclic GMP-dependent protein kinase (PKG) inhibitor, 8-bromo guanosine 3':5'-cyclic monophosphorothioate, Rp-isomer (Rp-8-bromo-cyclic GMPS; 10 microM). By contrast they were unaffected by the cyclic GMP-dependent protein kinase (PKG) inhibitor,8-bromo-guanosine 3':5'-cyclic monophosphorothioate, Rp isomer (Rp-8-bromo-cyclic GMPS; 10 MicroM).At the same concentrations the PKA inhibitor attenuated only the nerve-induced vasoconstrictor responses obtained in the presence of 8-bromo-cyclic AMP, whereas the PKG inhibitor did not modify that obtained in the presence of 8-bromo-cycic AMP or forskolin.5. Exposure to the protein kinase C (PKC) activator, phorbol 12-myristate 13-acetate (1 MicroM) enhanced nerve-evoked [3H]-noradrenaline release, and this effect was decreased by the PKC inhibitor, 2-[1-(3-dimethylaminopropyl)-indol-3-yl]-3-(-indol-3-yl) maleimide (GF 109203X; 100 nM). However, the latter drug did not modify the enhancing effect of 8-bromo-cyclic AMP on [3H]-noradrenaline release.6. It is concluded that activation of cyclic AMP-dependent protein kinase is involved in the enhancing effect of cyclic AMP-elevating compounds on prejunctional release of noradrenaline. In addition the results provide no clear-cut evidence for a vasodilator role of PKA. PMID- 8004412 TI - Resistance of Neosartorya fischeri to wet and dry heat. AB - Dry heat resistance parameters for Neosartorya fischeri ascospores were obtained at 90 degrees C and 95 degrees C under 30%, 40%, 50%, 60%, and 75% relative humidity (RH) conditions. The dry heat treated spores were exposed to saturated water vapor (for 20-24 h at 4 degrees C) prior to recovery in buffer held at two temperatures (0 degrees C and 80 degrees C). Approximately the same level of recovery was obtained at the two buffer temperatures except at the shortest heating times for the heat treatment carried at 30% and 40% RH, where the number of survivors was significantly higher for spores placed in the buffer held at 80 degrees C. The effect of this high temperature was attributed to heat activation of the ascospores that remained dormant during the dry heat treatment conditions mentioned above. The wet heat resistance of N. fischeri ascospores was also determined at temperatures ranging from 82.5 degrees C to 95 degrees C. The results indicate that as the RH decreased, the heat resistance of the ascospores increased. There were about four orders of magnitude difference in the heat resistance between wet heat (100% RH) and the lowest dry heat treatment condition (30% RH). PMID- 8004414 TI - Product development of AG-331 lyophilized powder for injection. AB - AG-331, a water-soluble glucuronate salt of a potential anticancer drug, was synthesized using a technology described as "Protein Structure-based Drug Design." A lyophilized product containing 44.4% (w/w) of AG-331, 55.6% (w/w) of mannitol and trace of water was developed for parenteral delivery of AG-331. The pre-lyophilized solution, which contains 2.0% (w/v) of AG-331 and 2.5% (w/v) mannitol can be aseptically filtered through commonly used 0.2-micron filters without significant AG-331 loss. The filter of choice was made of PTFE (polytetrafluoroethylene) membrane. The lyophilized product is stable under accelerated conditions for at least 6 months. The product can be sterilized with gamma-irradiation. The AG-331 reconstituted solution in 5% Dextrose Injection, USP is stable in PVC infusion bags for at least 2 days at 5 degrees C and 30 degrees C. PMID- 8004413 TI - IV fluid makers: preparation of sterile water for injection in a field setting. PMID- 8004415 TI - Approaches to reducing subvisible particle counts in lyophilized parenteral formulations. AB - Reduction in subvisible particle counts in parenteral formulations is an important requirement. Despite selection of best container/closure and use of processing conditions where the drug is most soluble and stable, lyophilized formulations often demonstrate problems of subvisible particle counts greater than the permitted compendial limits. We have studied some formulation and processing approaches with different compounds with the intention of developing lyophilized products, which after reconstitution, pass compendial subvisible particle limits for large volume parenterals (LVP). The approaches studied were targeted to reduce "intrinsic" subvisible particle counts and included the addition of a solubilizing agent, pH adjustment, charcoal treatment of the process solution, and use of a filter with finer pore size for filtering the solution prior to lyophilization. Although the relative efficiency of each of these parameters in reducing subvisible particle counts was found to be slightly different for each compound, the inclusion of a solubilizing agent and charcoal treatment of the processing solution were found to have the most pronounced effect. The combination of two or more parameters was often found to be even more effective. It is suggested that these approaches may be useful in developing other lyophilized products that yield low subvisible particle counts on reconstitution. PMID- 8004417 TI - PDA presentation at FDA Open Conference on Sterile Drug Manufacturing. Parenteral Drug Association. PMID- 8004416 TI - Photostabilization of dacarbazine with reduced glutathione. AB - Reduced glutathione was found to guard against photodecomposition (under fluorescent light) of the anticancer drug dacarbazine (DTIC). Increase in pH appeared to accelerate the degradation of DTIC within a pH range of 4.5-8.1. The stabilizing effect of reduced glutathione was found to increase with its concentration reaching an optimum value at 5 mg%. Increase of ionic strength slightly enhanced the photostability of DTIC solutions in pH 7 phosphate buffer (0.05 M). Different buffer systems at pH 4.5 did not significantly alter the degradation rate of the drug in the absence of reduced glutathione. However, in presence of reduced glutathione, dacarbazine appeared to be less stable in acetate buffer of pH 4.5. PMID- 8004418 TI - The biotest RCS air samplers in unidirectional flow. AB - When monitoring the microbiological quality of air in unidirectional air flow units the Biotest air sampler Reuter Centrifugal Sampler (RCS) is often used. In this unidirectional air flow the dispersion region of contaminants (disturbance region caused by turbulence) around the RCS sampler is much larger than that of undisturbed parallel air flow. The recently developed air sampler from Biotest, the RCS+, has a smaller and a different type of dispersion region (disturbance region) than that of the common RCS sampler. The differences must be taken into consideration when the two types of RCS air sampler are used within unidirectional air flow units, especially during aseptic operations in pharmaceutical production. PMID- 8004419 TI - Validation--how much can the world afford? Are we getting value for money? AB - The author raises questions not usually considered in discussions of validation: "How much validation can the world afford?," "Are we getting value for money?," and "What's in it for the patient?." The paper develops the theme that, while validation is undoubtedly important, the pharmaceutical industry has not given adequate thought as to whether the benefits of validation outweigh the costs in implementation of validation. PMID- 8004420 TI - International Regulatory Compliance. PMID- 8004421 TI - Fatal flaws.... PMID- 8004422 TI - Minimizing unnecessary repetition. PMID- 8004424 TI - The devil's in the details. PMID- 8004423 TI - Staffing implications: a legal update. PMID- 8004425 TI - How technology enhances total quality improvement. PMID- 8004426 TI - Morals: from Bobbit to Kevorkian. PMID- 8004427 TI - Reducing healthcare costs through co-op care. AB - The crisis of rising consumer costs in healthcare has its roots in the history of medicine combined with the public's perceived right to healthcare. To reduce costs, many institutions have reduced staff which, according to some critics, threatens quality of care. A true solution may be quite complex, requiring movement from the current paternalistic approaches typical of acute-care settings toward a cooperative model of illness care with an emphasis on wellness behavior. The concepts of efficacy and negotiated levels of health in the cooperative model care triad have been shown to reduce the cost of illness care while increasing satisfaction, client compliance and quality of care. PMID- 8004428 TI - Succession management: a model for developing nursing leaders. AB - Succession management is critical to all healthcare organizations as they respond to the cost-cutting initiatives brought about by the prospective payment era. This personnel management system ensures that motivated individuals enter and ascend the management hierarchy consistently. Such stabilization is reflected in turnover vacancy rates of < 12 percent and < 9 percent, respectively, at a time of unprecedented competition for professional nurses. This provides not only greater professional advancement but also stability for patient care delivery. PMID- 8004429 TI - Twenty-four hour care teams. AB - When faced with staff mix changes, nurse managers must clarify the underlying purpose so that the strategy selected will support the specific objective. Mix change options are reviewed and a two-dimensional philosophy regarding patient care teams is described. PMID- 8004430 TI - Nursing tools: a global perspective. PMID- 8004431 TI - Aseptic technique: covering all the bases. AB - An activity was developed which combines standards of practice, JCAHO indicators and a critical aspect of care. Included was development of an inservice on aseptic technique, a unique feature of which was a "practicum." Staff enjoyed the self-directed learning process. PMID- 8004432 TI - Cost awareness in emergency department nurses. AB - Incomplete charging of supplies was found to be responsible for significant dollar losses in the Emergency Department. A cost containment committee developed several strategies for cutting costs ranging from buying less expensive products to various educational efforts. Some improvement was noted and further research studies were designed to increase employee awareness of the cost of various items. PMID- 8004434 TI - Effective communication: gender issues. PMID- 8004433 TI - Nursing ethics committees--where are they? AB - When establishing Nursing Ethics Committees (NECs), statewide nursing organizations play an important role in developing and disseminating resources. The Connecticut Nurses Association Ethics and Human Rights Committee surveyed 85 healthcare facilities to identify active NECs. Representatives facilitated other committees by providing guidelines and assistance to those agencies developing NECs--the ultimate goal. PMID- 8004435 TI - Developing a unit-based journal club. PMID- 8004436 TI - 25 years: a slightly irreverent retrospective. AB - From 1970 when room rates soared to 50 dollars a day, to the reorganization occasioned by DRGs, and restructuring for healthcare reform in the 1990s; from the gleaming white supervisory nurse of yesteryear, through nursing's image crisis, to the vice presidents and case managers of today; from the rise of critical care units to the development of ethics committees, Nursing Management's editor chronicles and comments on the major (and sometimes minor) events of the last 25 years of nursing. PMID- 8004437 TI - Corticosterone effects on corticotropin-releasing hormone mRNA in the central nucleus of the amygdala and the parvocellular region of the paraventricular nucleus of the hypothalamus. AB - Using in situ hybridization histochemistry, we report differential expression of corticotropin-releasing hormone (CRH) mRNA in the central nucleus of the amygdala (CEA) and the parvocellular region of the paraventricular nucleus of the hypothalamus (PVN) following systemic treatment with corticosterone (CORT) in adrenally-intact rats. Both injection of low (1 mg/kg/day) and high (5 mg/day) CORT reduced CRH mRNA expression in the PVN in a dose-dependent manner, although it returned to normal at the low dose by 14 days. By contrast, the high dose of CORT increased CRH mRNA transiently in the CEA at 4 days, although the low dose of CORT decreased it at 14 days. In a second experiment, we implanted a slowly releasing CORT pellet for 2 weeks (200 mg, 60 day release) subcutaneously. This treatment produced an elevation of CRH mRNA in the CEA both at 1 and 2 weeks, whereas CRH mRNA in the PVN was decreased to a large extent as seen in the high CORT group of the first experiment. These results suggest that glucocorticoids can facilitate CRH mRNA expression in the CEA, a site implicated in anxiety and fear, while restraining the hypothalamic-pituitary-adrenal axis as indicated by the reduction in CRH mRNA in the PVN. PMID- 8004438 TI - Neuronal activity related to memory in the intermediate and medial part of the hyperstriatum ventrale of the chick brain. AB - The intermediate and medial part of the hyperstriatum ventrale (IMHV) in the forebrain of the domestic chick Gallus gallus domesticus has been shown in previous studies to be critically involved in the learning process of imprinting. In the present study, 1-day-old chicks were imprinted by exposing them to one of two artificial stimuli. 24 h later each chick was given a preference test in which the two stimuli were presented in sequence. A preference score, an index of the strength of imprinting (i.e., of learning), was calculated from approach activity during the preference test. The chicks were divided into groups with low, medium and high preference scores (corresponding to weak, medium and strong learning respectively) and coded so that all subsequent procedures were performed blind. Each chick was then anaesthetized and spontaneous action potentials recorded extracellularly from groups of neurones in the left IMHV. The mean neuronal firing rate in chicks with medium and high preference scores was significantly greater than that in chicks with low preference scores. This relation between neuronal activity and preference score was not attributable to the chicks' locomotor activity per se. The results demonstrate an association between spontaneous electrical activity in the left IMHV and a measure of learning 1 day after the learning occurred. PMID- 8004439 TI - NMDA receptor binding in rodent suprachiasmatic nucleus. AB - NMDA receptors are thought to mediate effects of light on circadian rhythms and on immediate-early gene expression in the suprachiasmatic nucleus (SCN), the primary circadian pacemaker in mammals. The present study characterized NMDA receptors in autoradiographs of SCN incubated with the NMDA antagonist [3H]MK 801. In both rat and hamster, [3H]MK-801 binding did not delineate the SCN and was fairly uniformly distributed across the SCN region. Binding levels were unaffected by circadian time, light vs. dark conditions, or enucleation. Scatchard analyses revealed species differences in both receptor number and affinity in the SCN. The [3H]MK-801 binding sites characterized in this study could mediate the NMDA antagonist-sensitive effects of light on the SCN and circadian rhythms. PMID- 8004440 TI - Role of neuron soma firing in the restoration of neurotensin store in sympathetic preganglionic neuron terminals after stimulus-evoked depletion. AB - We have previously shown that prolonged preganglionic stimulation (e.g. 40 Hz 20 min) depletes the neurotensin (NT) store of preganglionic axon terminals in the stellate ganglion (SG) of the cat and that replenishment of the store requires several days. The present study investigates the mechanisms which control turnover of the NT store in sympathetic preganglionic axon terminals. NT content of the SG and of the preganglionic axons which innervate it was determined by radioimmunoassay in the anesthetized cat. This study shows that, during the 24 h after 40-Hz 20-min stimulation of the preganglionic input to the SG, the rate of NT accumulation proximal to a ligature on the stimulated input is three times that observed in the control. The poststimulus increase in NT accumulation rate is prevented by treatment with protein-synthesis inhibitors. When the centripetal propagation of action potentials from the stimulus site on the preganglionic axons is prevented by a tetrodotoxin block applied locally during the stimulation period, the poststimulus increase in NT accumulation rate and the replenishment of the store are both prevented. These data suggest that the level of activity of the neuron regulates NT supply to the axon terminals, presumably by regulating NT synthesis. Thus, in the sympathetic preganglionic neuron, the action potential provides a mechanism for matching peptide synthesis to release. PMID- 8004441 TI - In vitro and in vivo evidence of neurotensin release from preganglionic axon terminals in the stellate ganglion of the cat. AB - We have previously shown that the neurotensin (NT) store in preganglionic axon terminals of the cat stellate ganglion (SG) is reversibly depleted by prolonged preganglionic stimulation. The present study addresses the questions of whether the preganglionic axon terminals release NT in response to depolarizing stimuli in vitro and whether in vivo NT is released by the tonic firing of the sympathetic preganglionic neurons. Slices of the SG of the anaesthetized cat, maintained in oxygenated Ringer solution, released NT. The efflux increased when the K concentration was increased from 5 to 25 or 45 mM or when veratridine was added to the medium. In Ca-free medium, efflux was suppressed. The effect of veratridine was blocked by tetrodotoxin (TTX). In awake, freely moving cats, in which TTX was applied for 4 days to the preganglionic input of the right SG, the NT content of this ganglion doubled by comparison with the left SG. Since NT accumulates proximal to a ligature on the preganglionic input of the SG, the increased NT content is likely to result from suppression of action potential dependent release while influx into the terminals persists. This result suggests that the steady state of the NT store in sympathetic preganglionic terminals is the result of a steady influx from the soma balanced by action potential dependent loss, presumably release. PMID- 8004442 TI - Social isolation-induced enhancement of the psychomotor effects of morphine depends on corticosterone secretion. AB - Short-term social isolation has been shown to increase individual reactivity to addictive drugs, although the biological factors involved in this effect are largely unknown. In this study, we investigated the influence of corticosterone secretion on the effects of social isolation on the response to opioids. The effects of social isolation on morphine-induced locomotor activity were compared in: (i) animals with an intact hypothalamo-pituitary-adrenal (HPA) axis; (ii) animals in which stress-induced corticosterone secretion was blocked by adrenalectomy. The animals in the latter group were implanted with subcutaneous corticosterone pellets (50 mg), which slowly release corticosterone, producing stable plasma levels within the physiological range. Social isolation increased the locomotor response to morphine (2 mg/kg s.c.) in animals with an intact HPA axis, but not in animals in which corticosterone secretion was blocked. These results suggest that corticosterone secretion is required for the expression of the enhanced locomotor response to opioids induced by isolation. Since an enhanced locomotor reactivity to addictive drugs has been found to be frequently associated with an enhanced vulnerability to drug self-administration, these findings suggest a role for glucocorticoids in the vulnerability to the reinforcing effects of opioids. PMID- 8004443 TI - Epileptogenic actions of xanthines in relation to their affinities for adenosine A1 receptors in CA3 neurons of hippocampal slices (guinea pig). AB - In order to analyze the epileptogenic mechanisms of caffeine and related xanthines, putative effects of these drugs were studied on adenosine receptors of CA3 neurons in hippocampal slices. Epileptogenic concentrations of different xanthine derivatives strongly correlated with their affinities for the inhibitory A1 adenosine receptor subtype. The A1 receptor agonists adenosine and R-PIA reversibly depressed xanthine-induced epileptic activity without effects on the resting membrane potential or on spontaneously occurring action potentials. These findings suggest that the epileptogenic potency of xanthines is primarily due to the blockade of the A1 receptors through an abnormal rise of intracellular cAMP and to the excessive transmembrane calcium fluxes underlying paroxysmal depolarization shifts. PMID- 8004444 TI - Differential regulation of glutamate decarboxylase and preproenkephalin mRNA levels in the rat striatum. AB - The mRNA levels encoding for the enzyme glutamate decarboxylase (GAD67) and the peptide enkephalin were measured in the striatum of adult and 15 day-old rats by in situ hybridization histochemistry and radioautography after neonatal injections of 6-hydroxydopamine or after acute pharmacological blockade of dopamine receptors with haloperidol or sulpiride. In adult rats injected as neonates with 6-hydroxydopamine or treated with the D1/D2 dopamine receptors antagonist, haloperidol, an increase in preproenkephalin and GAD67 mRNA levels was measured in the striatum. The D2 dopamine receptor antagonist, sulpiride, did not change the mRNA levels of either GAD67 or PPE in the striatum. In 15-day-old rats, neonatal 6-hydroxydopamine or haloperidol treatment resulted in increased preproenkephalin but unchanged GAD67 mRNA levels compared to controls. In these 15-day-old rats, however, sulpiride produced an increase in GAD67 but not preproenkephalin mRNA levels. Intrastriatal injections to adult rats of pertussis toxin which uncouples Gi/Go proteins from their receptors resulted in a dramatic increase in preproenkephalin without concomitant change in GAD67 mRNA levels. Altogether, these results show that GAD67 and preproenkephalin mRNA levels are modulated in parallel in adult but not in 15 day-old rats after 6-hydroxydopamine injections or dopaminergic blockade. In keeping with evidence of a co localization of GAD67 and preproenkephalin mRNAs in some striatal neurons, the results indicate that these two mRNAs can be differentially regulated in the same neurons. In addition, the differential effect of haloperidol, sulpiride or pertussis toxin on GAD67 and preproenkephalin mRNA levels suggests that these two mRNAs are regulated through different dopamine receptor subtypes. PMID- 8004445 TI - Ultrastructural localization of butyrylcholinesterase on neurofibrillary degeneration sites in the brains of aged and Alzheimer's disease patients. AB - Butyrylcholinesterase histochemical techniques were applied to vibratome sections of several cortical areas from the brains of non-demented aged and of Alzheimer's disease patients. At the light microscope level, all the senile plaque types and all the structures with neurofibrillary degeneration showed butyrylcholinesterase reaction product, whereas nearby neuronal perikarya and axons on the same slides remained unstained. Areas containing stained elements were selected, re sectioned, and finally observed under the electron microscope. Focusing on the sites of neurofibrillary degeneration, butyrylcholinesterase reaction product was found in both intra- and extracellular neurofibrillary tangles, in neurites associated with plaques, and in neuropil threads that were either axons or dendrites. This reaction product was exclusively located over filament bundles, and sometimes covered them so completely that they could not be identified. When the filaments were only partially covered, it was possible to identify them as either paired helical filaments or straight filaments. Occasionally, neurofibrillary tangles, neuropil threads and plaque-associated neurites, all of them containing either paired helical filaments or straight filaments, were found to be completely free of butyrylcholinesterase reaction product. The origin and possible role of butyrylcholinesterase, which is ultrastructurally localized over elements presenting neurofibrillary degeneration, is discussed. PMID- 8004446 TI - Morphological study of long axonal projections of ventral medullary inspiratory neurons in the rat. AB - The aim of this study was to examine medullary and spinal axonal projections of inspiratory bulbospinal neurons of the rostral ventral respiratory group (VRG) in the rat. A direct visualization of long (9.8-33 mm) axonal branches, including those projecting to the contralateral side of the medulla oblongata and the spinal cord, was possible due to intracellular labeling with neurobiotin and long survival times (up to 22 h) after injections. Seven of the nine labeled neurons had bilateral descending axons, which were located in discrete regions of the spinal white matter; ipsilateral axons in the lateral and dorsolateral funiculus, contralateral in the ventral and ventromedial funiculus. The collaterals issued by these axons at the mid-cervical level formed close appositions with dendrites of phrenic motoneurons, which had also been labeled with neurobiotin. None of these collaterals crossed the midline. The significance of this finding is discussed in relation to the crossed-phrenic phenomenon. Additional spinal collaterals were identified in the C1 and T1 segments. Within the medulla, collaterals with multiple varicosities were identified in the lateral tegmental field and in the dorsomedial medulla (in the hypoglossal nucleus and in the nucleus of the solitary tract). These results demonstrate that inspiratory VRG neurons in the rat have some features which have not been previously described in the cat, including frequent bilateral spinal projection and projection to the nucleus of the solitary tract. In addition, this study shows that intracellular labeling with neurobiotin offers an effective way of tracing long axonal projections, supplementing results previously obtainable only with antidromic mapping, and providing morphological details which could not be observed in previous studies using labeling with horseradish peroxidase. PMID- 8004447 TI - The effects of chronic continuous versus intermittent levodopa treatments on striatal and extrastriatal D1 and D2 dopamine receptors and dopamine uptake sites in the 6-hydroxydopamine lesioned rat--an autoradiographic study. AB - The effects of chronic 'continuous' infusion and 'intermittent' modes of levodopa/carbidopa administration on apomorphine induced circling behaviour, DA uptake sites (labelled with [3H]mazindol) and D1 and D2 DA receptor binding (labelled with [3H]SCH 23390 and [3H]sulpiride, respectively) were investigated in rats with unilateral 6-OHDA lesions of the medial forebrain bundle. The circling behaviour in response to apomorphine was greatly enhanced following chronic 'intermittent' but not 'continuous' levodopa treatments. Following the 'intermittent' regime, the lower dose of apomorphine induced a period of intense circling with delayed onset and rapid offset, than in rats given either 'continuous' infusion of levodopa or saline. The 6-OHDA lesion itself induced gross depletion of [3H]mazindol binding in all striatal subregions, NAc and OT, but not frontal cortex. [3H]Sulpiride binding in the ventrolateral striatal quadrant was increased on the denervated side and this correlated with the peak contralateral turns in response to 0.5 mg/kg apomorphine challenge. This asymmetry in striatal [3H]sulpiride binding was reduced in both groups of rats receiving levodopa. [3H]sulpiride binding in the NAc and OT and [3H]SCH 23390 binding in the striatum, NAc, OT and SNr were unaffected by DA denervation or either regime of levodopa treatments. 'Continuous' infusion and not 'intermittent' injections of levodopa reduced [3H]mazindol binding in the striatal subregions and the frontal cortex on both the denervated and intact sides. The potentiation of the behavioural response to apomorphine by chronic 'intermittent' levodopa treatment does not correspond with the levodopa induced alterations in striatal or extrastriatal DA receptors. In the same group of animals the narrowing of the duration of response to the lower dose of apomorphine may mimic the fluctuations in response to levodopa, seen clinically in long-term levodopa treated parkinsonian patients. PMID- 8004448 TI - The medial preoptic area is involved in both sexual arousal and performance in male rats: re-evaluation of neuron activity in freely moving animals. AB - A total of 74 single unit activities was recorded from the medial preoptic anterior hypothalamic continuum (MPOA) during free copulatory behavior of male rats. Forty-six units (62.2%) showed changed activities during at least one phase of male copulatory movements; 26 units (35.1%) increased in the firing rate during pelvic thrusting; 32 units (43.2%) increased in activity during backward jumping immediately after intromission; only one unit (1.4%) showed decreased firing rate during thrusting and backward jumping; 12 units (16.2%) increased in activity during pursuit of a female; 19 units (25.7%) were suppressed during genital grooming. Furthermore, 67 units (90.5%) showed a significant change in activity throughout a series of copulatory behavior. From the introduction of a female up to ejaculation, relatively large number of units increased in the firing rate above the value during pre-introduction adaptation period. During postejaculatory interval, however, most units decreased in activity below the level during copulation. These results strongly suggest that the MPOA is involved in both sexual arousal and performance in male rats. PMID- 8004449 TI - Physiological roles of glycine and gamma-aminobutyric acid in dissociated neurons of rat visual cortex. AB - The effects of glycine (Gly) and gamma-aminobutyric acid (GABA) on the neurons acutely dissociated from rat visual cortex (VC) were investigated in the whole cell mode using a conventional patch-clamp technique. GABA and Gly evoked Cl- currents (ICl) in a concentration-dependent manner at a holding potential (VH) of -50 mV. The half maximum effective concentrations (EC50) were 4.64 x 10(-6) M for GABA and 6.67 x 10(-5) M for Gly. Strychnine and bicuculline reversively inhibited both 10(-5) M GABA- and 10(-4) M Gly-induced ICl in a concentration dependent manner. The half maximum inhibitory concentrations (IC50) of strychnine on GABA- and Gly-induced currents were 4.00 x 10(-6) M and 8.26 x 10(-8) M, respectively. The IC50 values of bicuculline on GABA and Gly responses were 1.18 x 10(-6) M and 2.97 x 10(-4), respectively. GABA at 10(-5) M, which is near the EC50 of the GABA response, induced ICl in all neurons tested (n = 83). However, Gly of 10(-4) M, which is also near the EC50 of the Gly response, induced ICl in 34 out of 83 neurons tested (41%). Moreover, the maximum amplitude of the Gly response was about 60% of that of the GABA response. On the other hand, the enhancement of N-methyl-D-aspartate (NMDA, 3 x 10(-4) M) response by Gly (10(-6) M) was observed in all neurons (n = 36) whether they had the Gly-induced ICl or not.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8004450 TI - Developmental immunohistochemistry of bifunctional protein in human brain. AB - Immunohistochemical studies of a peroxisomal enzyme, bifunctional protein, were performed on human brains (occipital cortex, cerebellum, pons) from fetus to young adult. Bifunctional protein-positive neurons appeared at 23-25 weeks of gestation in the facial nuclei of pons, at 27-28 weeks in the occipital cortex and Purkinje cells of vermis, and at 36-38 weeks in the Purkinje cells of the cerebellar hemisphere and pontine nuclei. They then increased in number with gestational age. However, bifunctional protein-positive glia appeared early in the occipital deep white matter at 17-20 weeks of gestation, their appearance shifting from the deep to the superficial white matter with increasing age. These results suggest that bifunctional protein is closely related to neuronal maturation and gliogenesis of premyelination in the human brain during development as other peroxisomal enzymes. PMID- 8004451 TI - Muscarinic cholinergic receptor binding in rat brain following traumatic brain injury. AB - Recent evidence suggests that excessive activation of muscarinic cholinergic receptors (mAChRs) contributes significantly to the pathophysiological consequences of traumatic brain injury (TBI). To examine possible alterations in mAChRs after TBI, the affinity (Kd) and maximum number of binding sites (Bmax) of mAChRs in hippocampus, neocortex, brain stem and cerebellum were determined by [3H]QNB binding. Three groups of rats were examined: 1 h post-TBI (n = 21), 24 h post-TBI (n = 21) and sham-injured rats (n = 21). Kd values were significantly higher in hippocampus and brain stem at 1 but not 24 h post-TBI compared with sham-injured controls (P < 0.05). Kd values did not significantly differ in neocortex and cerebellum at 1 or 24 h post-TBI compared with sham-injured controls. Bmax values did not significantly differ in any brain areas at 1 or 24 h post-TBI compared with sham-injured controls. These results show that TBI significantly decreases the affinity of mAChRs in hippocampus and brain stem at an early stage post-TBI, which may contribute to desensitization of mAChRs after TBI. The findings of no change in Bmax values are consistent with a transient elevation in ACh concentrations after TBI. PMID- 8004452 TI - The CCKA receptor antagonist devazepide does not modify opioid self administration or drug discrimination: comparison with the dopamine antagonist haloperidol. AB - We previously reported that the selective cholecystokininA (CCKA) receptor antagonist, devazepide, blocked the acquisition of a morphine conditioned place preference (ref 28). An interpretation of this finding is that devazepide may either affect an opioid discriminative stimulus and/or modify the rewarding properties of opioids. The present study was designed to investigate these issues by determining the effect of equivalent doses of devazepide in a morphine drug discrimination paradigm and a model of heroin self-administration. In each case, devazepide (0.001-1 mg/kg) was ineffective, i.e there was no antagonism of a morphine discriminative cue, and in a separate group of rats trained to self administer heroin (0.03 mg/kg/infusion, FR5 schedule, 1h per day), devazepide did not alter the pattern of heroin responding. Because of evidence implicating an interaction between accumbens CCK and dopamine (DA) systems and evidence suggesting an apparent differential involvement of DA in opioid place conditioning, self-administration and drug discrimination behaviour, the effect of the DA antagonist haloperidol was examined in the latter two paradigms. In each test, haloperidol produced an effect inconsistent with a direct DAergic involvement. In a final study the CCKB antagonist L365-260 was also found not to affect an opioid discriminative cue. The present results therefore cast doubt on the potential utility of selective CCKA antagonists as treatments for opioid abuse, and further suggest that CCKB antagonists may not potentiate the subjective effects of opioids, an important finding considering that such drugs have been proposed as adjuncts to opioid therapy for the treatment of pain relief. PMID- 8004453 TI - beta-Amyloid precursor protein fragments and lysosomal dense bodies are found in rat brain neurons after ventricular infusion of leupeptin. AB - Infusion of the serine and thiol protease inhibitor, leupeptin, is known to cause a reduction of fast axoplasmic transport, and accumulation of lysosomal dense bodies in neuronal perikarya. We have found these dense bodies in hippocampal and cerebellar neurons contain ubiquitin conjugated proteins. We now demonstrate that these accumulated neuronal lysosomes are labeled by antisera to the cytoplasmic, transmembrane and extracellular domains of beta-amyloid precursor protein (APP) and also that lysosomal APP is fragmented. This in vivo model confirms that neurons can process APP via a lysosomal pathway and that neuronal lysosomes in vivo contain both N-terminal and potentially amyloidogenic C-terminal fragments of APP. We also show that increased APP immunoreactivity after leupeptin treatment is seen first in neurons and later in astrocytes. On recovery from infusion, APP N-terminal immunoreactivity diminishes whilst C-terminal reactivity remains in neurons. These findings are consistent with production in whole brain of potentially amyloidogenic fragments of APP within neuronal lysosomes in perikarya and dendrites implying that neurons may play a role in forming the beta amyloid of plaques. PMID- 8004454 TI - Reversal of dexfenfluramine-induced anorexia and c-Fos/c-Jun expression by lesion in the lateral parabrachial nucleus. AB - The external subdivision of the lateral parabrachial nucleus (LPBE) shows strong Fos-like immunoreactivity (FLI) following anorectic doses of the indirect serotonin agonist dexfenfluramine (DFEN). In an effort to determine the contribution of the LPBE to DFEN-induced anorexia, bilateral ibotenate lesions were made in the LPBE, and the effects of the lesion on DFEN-induced anorexia and FLI as well as c-Jun-like immunoreactivity (JLI) were examined. It was found that LPBE lesion significantly attenuated DFEN anorexia: in a 1-h food intake test following 24-h food deprivation, DFEN (2 mg/kg) suppressed food intake by 60% in intact rats but only 34% in rats with LPBE lesions. In addition to this behavioral change, LPBE lesion completely abolished DFEN-induced FLI and JLI in the lateral subdivision of the central nucleus of the amygdala (CeL) and laterodorsal subdivision of the bed nucleus of stria terminalis (BSTLD), both of which showed strong FLI and JLI in intact rats. DFEN-induced FLI and JLI in other brain regions were not affected by LPBE lesion, including the ventromedial and lateral hypothalamus, caudate-putamen, and the nucleus of the solitary tract (NST). The parallel loss of DFEN-induced anorexia and FLI/JLI following LPBE lesion raises the novel possibility that LPBE-CeL/BSTLD pathway may be involved in DFEN anorexia. PMID- 8004455 TI - Changes in [3H]PAF binding and PAF concentrations in gerbil brain after bilateral common carotid artery occlusion: a quantitative autoradiographic study. AB - This study investigated the distribution of platelet activating factor (PAF) binding sites in the brain and their involvement in global ischemia in a model of bilateral common carotid occlusion in the gerbil. In sagittal sections of gerbil brain, labeling with [3H]PAF was mainly located in the cortex, hippocampus and cerebellum. The corpus striatum, the superior and inferior colliculi showed lower binding, while the thalamus was only weakly labeled. Scatchard analysis of the data obtained from displacement curves with unlabeled PAF revealed the presence of one or two populations of binding sites with different affinity constant values depending on the brain structures. When the gerbils were submitted to 10 min ischemia, similar autoradiography with [3H]PAF demonstrated a dramatic reduction of labeling in all brain structures, particularly in the hippocampus. Immunoreactive endogenous PAF concentrations in brain tissues showed a marked increase in ischemic animals: (8977.3 +/- 1113 pg/g wet weight) as compared to sham-operated control: (997.7 +/- 77 pg/g wet weight). Endogenous PAF levels returned to basal values following 30 min reperfusion. These results indicate that PAF may be involved in the early stages of brain ischemia in the gerbil and suggest that endogenous PAF produced during ischemia may contribute to the down regulation of [3H]PAF binding sites in the brain. PMID- 8004456 TI - Distribution of target cells for 1,25-dihydroxyvitamin D3 in the brain of the yellow bellied turtle Trachemys scripta. AB - Five h after injection of tritiated 1,25-dihydroxyvitamin D3 into Trachemys scripta, neurons with nuclear concentrations of radioactivity were identified in distinct regions within the central nervous system. Coinjection of a 100-fold excess of non-labeled 1,25-dihydroxyvitamin D3 abolished or reduced the specific nuclear binding of tracer. Target neurons were present in ventral periventricular brain regions including tuberculum olfactorium, nucleus accumbens, cortex piriformis, primordium hippocampi, nucleus striae terminalis, dorsal ventricular ridge, amygdala, nucleus infundibularis and tectum opticum. With the exception of the nucleus infundibularis and the tectum opticum, target neurons can be continuously followed from the ventrolateral nucleus accumbens throughout the nucleus striae terminalis into the amygdala. The general distribution of target neurons is similar to that described for rodents but more restricted to the above regions. The results show that target neurons for vitamin D are located in brain regions including several components of the limbic and thalamic systems in which gonadal steroids as well as aminergic and peptidergic messengers exert their actions. Vitamin D, the heliogenic steroid hormone, may therefore be involved in the orchestration of season-specific processes such as reproduction and related behaviors. PMID- 8004457 TI - Binaural response patterns in subdivisions of the medial geniculate body. AB - Auditory evoked potentials (AEPs) to binaural click stimulation were examined in the ventral (MGv) and caudomedial (MGcm) subdivisions of the medial geniculate body (MG) in guinea pigs. Binaural stimulation caused a decrease in amplitude for the response component recorded from the MGv, but an increase in amplitude for the AEP component recorded from the MGcm. Findings suggest that the evoked responses recorded from MGv and MGcm are functionally distinct. The inhibitory binaural response (BR) pattern seen in MGv was similar to that of the middle latency response (MLR) component recorded over the temporal cortex, while the additive BR pattern typical of the MGcm was similar to that of the surface midline MLR component. Furthermore, these data imply that the binaural response patterns seen in the primary and non-primary auditory cortex may be processed and encoded at the thalamic level. It is concluded that the distinct BR patterns noted for the two MG subdivisions reflect the predominant type of binaurally responsive neurons within the respective pathways. PMID- 8004458 TI - Distribution and characteristics of a 90 kDa protein, KG-CAM, in the rat CNS. AB - The distribution of a 90 kDa protein, termed KG-CAM, was examined in the developing and adult rat central nervous system (CNS) using the monoclonal antibody 11-59. The amino acid sequence of this protein revealed a sequence homology with a group of chick cell adhesion molecules from the immunoglobulin superfamily: DM-GRASP; SC1; and BEN. Immunolabeling of cells cultured from the embryonic and neonatal rat brain demonstrates that the protein recognized by 11 59 is on the external surface of a subpopulation of neurons and a limited population of glial cells. When the 11-59 antibody was used to stain sections of the adult brain and spinal cord, a number of different structures were labeled. The most intense immunoreactivity was found in the somatosensory system, the basal ganglia, the cortex, the olfactory system, and the circumventricular organs. One of the more interesting aspects of KG-CAM is the spatially and temporally regulated patterns of expression observed during the development of the CNS. For example, the dendrites of layer II pyramidal cells in the granular retrosplenial cortex are immunopositive for 11-59 while the dendrites are in the process of bundling in layer I, but not before bundling begins or after the process is completed. These findings reveal the varied roles of this adhesion molecule in the developing brain and spinal cord, as well as its potential role in the maintenance of the structural integrity of the adult CNS. PMID- 8004459 TI - Photoperiodic effects on puberty and specific 2-[125I]iodomelatonin binding sites in Siberian hamsters. AB - When juvenile male Siberian hamsters are transferred from a long photoperiod to a short photoperiod, sexual maturation is greatly delayed by a pineal-dependent process. We hypothesized that the eventual onset of puberty during short photoperiod exposure may be caused by a loss of receptors for the pineal hormone, melatonin. This study quantitated specific 2-[125I]iodomelatonin binding sites in the suprachiasmatic nuclei and pars tuberalis of Siberian hamsters exposed to short photoperiod (10 h light per day) for either 12 or 30 weeks and in hamsters exposed to long photoperiod (16 h light per day) for the same time intervals. Photoperiodic exposure significantly affected testes weight. The hamsters exposed to long photoperiod for either 12 or 30 weeks had mean tests weights > 700 mg, in contrast to hamsters in short photoperiod for 12 weeks (mean testes weights < 30 mg) or 30 weeks (mean testes weights approximately 350 mg). The affinity of specific 2-[125I]iodomelatonin binding sites in both regions was significantly lower in hamsters exposed to short photoperiod as compared to hamster exposed to long photoperiod, at either 12 or 30 weeks. In contrast, there were no effects of photoperiod or duration of exposure on the density of specific 2 [125I]iodomelatonin binding sites in either the suprachiasmatic nuclei or the pars tuberalis. Furthermore, a change in the affinity of the specific 2 [125I]iodomelatonin binding sites in the suprachiasmatic nuclei was observed between the hamsters housed in short photoperiod for 12 weeks (sexually immature) and the hamsters housedin short photoperiod for 30 weeks (undergoing puberty).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8004460 TI - Prolonged antinociception following carbon dioxide anesthesia in the laboratory rat. AB - In the laboratory rat, inhalation (30 s) of high (> 70%) CO2 concentrations resulted in short-term (1-3 min) anesthesia, followed by a prolonged (up to 60 min) mild antinociception. Exposure to 100% CO2 resulted in significant thermal (hot-plate, 52 degrees, and tail-flick) and mechanical (tail-pinch, 886 g force) antinociception. Control animals, placed in the same chamber filled with air, showed no such effects. Rats exposed to 70% CO2 exhibited effects on the hot plate comparable to those seen after inhalation of 100% CO2, indicating that the response is not due to CO2-induced hypoxia. Additionally, recovery from halothane induced anesthesia of comparable duration did not result in antinociception, confirming that anesthesia alone is not sufficient to produce the effect. Pretreatment with the opiate antagonist naltrexone (0.1-10 mg/kg i.p.) did not diminish the CO2-induced antinociception, suggesting that endogenous opioids are not obligatory in the mechanism of this response. Furthermore, hypophysectomy abolished hot-plate antinociception in animals exposed to 100% CO2 while sham treated controls exhibited a pattern of hot-plate responses similar to that reported above. Taken together, these findings show that: (1) recovery from CO2 induced anesthesia results in a prolonged mild antinociception, detectable with thermal and mechanical nociceptive tests; and (2) this response may represent a novel from of environmentally induced antinociception, mediated by a non-opiate hormonal substance. PMID- 8004461 TI - Effects of 21 days treatment with fluoxetine on stimulated endogenous 5 hydroxytryptamine overflow in the rat dorsal raphe and suprachiasmatic nucleus studied using fast cyclic voltammetry in vitro. AB - Changes in the extracellular concentration of 5-HT evoked by electrical stimulation of brain slices containing either dorsal raphe nucleus (DRN) or suprachiasmatic nucleus (SCN) from rats treated for 21 days with fluoxetine (5 mg/kg; i.p.) or water were monitored using fast cyclic voltammetry (FCV). Stimulated 5-HT overflow was enhanced significantly in both brain regions after 21 days treatment with fluoxetine but there was no change in the half time for re uptake (t1/2). Concentration response curves for inhibition of electrically stimulated 5-HT overflow by 8-OH-DPAT (5-HT1a receptor agonist) or RU24969 (5 HT1b receptor agonist) in the DRN or SCN respectively were obtained in slices prepared from both groups of animals. There was a significant shift to the right in the dose-response curve for RU24969 in the SCN in fluoxetine treated animals but a shift to the left for the dose-response curve for 8-OH-DPAT in the DRN. These data suggest that down regulation of the 5-HT1b autoreceptors occurs in an axon terminal region (SCN) but that there is a sensitisation of 5-HT1a autoreceptor mechanisms controlling 5-HT overflow in the DRN. PMID- 8004462 TI - Regulation of gamma-aminobutyric acidB (GABAB) receptors in cerebral cortex during the estrous cycle. AB - We examined binding of the GABAB receptor agonist baclofen to brain synaptic membranes as a function of the natural variations in gonadal steroids that occur during the estrous cycle of the adult rat. We found that the binding of baclofen to neocortical membranes varied systematically as a function of the estrous cycle, with the lowest binding occurring during the estrus stage. Binding to archicortical (hippocampal) and hypothalamic preparations also varied with the estrous cycle, except that the lowest level of binding in these latter cases occurred during the diestrus stage. The variation of [3H]baclofen binding during the estrous cycle was different with respect to the binding of [3H]muscimol, an agonist for GABAA receptors, and [3H]8-hydroxy-2-(di-n-propylamino)tetralin (8-OH DPAT), an agonist for serotonin 5-HT1A receptors that shares similar G proteins and effectors with GABAB receptors. Saturation binding studies of cortical GABAB receptors showed that apparent receptor density (Bmax) rather than affinity (Kd) best accounted for the change in binding during the estrous cycle in that Bmax, like total specific binding, was at a minimum during the estrus stage. The robust regulation of GABAB receptors in neocortex was unexpected and its functional significance is at present unknown. However, the correlation of the menstrual cycle with mood and other behavioral changes, and the correlations of the estrous and menstrual cycles with seizure susceptibility, may somehow depend upon hormonal regulation of transmitter systems such as the one we have observed here. PMID- 8004463 TI - Brain uptake of trace metals, zinc and manganese, in rats. AB - The brains of rats injected intravenously with 65ZnCl2 or 54MnCl2 were subjected to high resolution autoradiography. 65Zn and 54Mn were largely concentrated in choroid plexus 1 h after injection and then gradually decreased, with increases in other brain regions, suggesting that both metals were taken up gradually into brain mainly via cerebrospinal fluid in the choroid plexus. By 3 days after injection, relatively high level of 65Zn was seen in the dentate gyrus and CA3 region of the hippocampus and in the cerebral cortex. The level of 54Mn was also high in the former, while relatively low in the latter. PMID- 8004464 TI - Induction of spinal NADPH-diaphorase by nerve injury is attenuated by adrenal medullary transplants. AB - Persistent sensory abnormalities consequent to injury may involve prolonged neuroplastic changes in the spinal cord similar to those in long-term potentiation. Molecular markers, like the putative nitric oxide synthase, nicotinamide adenine dinucleotide phosphate diaphorase (NADPH-d), can be useful indicators of increased neuronal activity. Peripheral nerve injury markedly increased NADPH-d-labeling in sensory regions of the spinal cord, paralleling induction of abnormal pain (hyperalgesia). Both NADPH-d activation and hyperalgesia were reversed by transplantation of opioid/catecholamine-producing adrenal medullary tissue into the spinal subarachnoid space. These results suggest that adrenal medullary transplants can attenuate abnormal neuronal activity consequent to injury. PMID- 8004465 TI - GABA in the inferior colliculus plays a critical role in control of audiogenic seizures. AB - Previous studies have implicated a decreased efficacy of GABA as an important defect subserving the audiogenic seizures of the genetically epilepsy-prone rat (GEPR-9). The inferior colliculus (IC) is a critical site for audiogenic seizure (AGS) initiation, and the pontine reticular formation (PRF) is implicated in the propagation of AGS and in other generalized seizure models. The present study observed that microinjection of baclofen, a GABA-B receptor agonist, into IC protects against AGS, and blockade of the breakdown of endogenous GABA by gabaculine, a GABA transaminase inhibitor, increased GABA levels and blocked AGS susceptibility in the GEPR-9. Microinjection of baclofen or gabaculine into the PRF reduced AGS severity, but the doses required were considerably greater and the degree of anticonvulsant effect was less. Uptake of [3H]GABA into GEPR-9 synaptosomes from the IC is significantly increased as compared to normal, which could contribute to the diminished effectiveness of GABA in the GEPR-9. Previous studies indicate that GABA-A receptor agonists block AGS with IC microinjection, and recent data indicate that blockade of GABA uptake in this nucleus significantly reduced AGS severity. These data taken together strongly support the critical importance of the defect in GABA function in the IC in modulating susceptibility to audiogenic seizure initiation in the GEPR-9. PMID- 8004466 TI - Lysosomal abnormalities in degenerating neurons link neuronal compromise to senile plaque development in Alzheimer disease. AB - Antibodies to the lysosomal hydrolases, cathepsins B and D and beta hexosaminidase A, revealed alterations of the endosomal-lysosomal system in neurons of the Alzheimer disease brain, which preceded evident degenerative changes and became marked as atrophy, neurofibrillary pathology, or chromatolysis developed. At the earliest stages of cell atrophy, hydrolase-positive lysosomes accumulated at the basal pole and then massively throughout the perikarya and proximal and proximal dendrites of affected pyramidal neurons in Alzheimer prefrontal cortex and hippocampus, far exceeding the changes of normal aging. Secondary lysosomes as well as tertiary residual bodies (lysosomes/lipofuscin) increased implying stimulated, autophagocytosis and lysosomal system activation. Less affected brain regions, such as the thalamus, displayed similar though less extensive alterations. Certain thalamic neurons exhibited a distinctive lysosome related abnormality characterized by the presence of cell surface blebs of varying size and number filled with intense hydrolase immunoreactivity. At more advanced stages of degeneration in still intact neurons, hydrolase-positive lipofuscin, particularly in the form of abnormally large aggregates, nearly filled the cytoplasm. Similar lipofuscin aggregates were observed in abundance in the extracellular space following cell lysis and were usually associated with deposits of the beta-amyloid protein. Degenerating neurons and their processes were the major source of these aggregates within senile plaques which contained high concentrations of acid hydrolases. We have shown in previous studies that these lysosomal hydrolases in plaques are enzymatically-active. The persistence of lysosomal structures in the brain parenchyma after neurons have degenerated is a striking and potentially diagnostic feature of Alzheimer disease which has not been observed, to our knowledge, in other degenerative diseases. The lysosomal response in degenerating Alzheimer neurons represents a probable link between an early activation of the lysosomal system in at-risk, normal-appearing neurons and the end-stage contribution of lysosomes to senile plaque formation and emphasizes a slowly progressive disturbance of the lysosomal system throughout the development of Alzheimer disease. PMID- 8004467 TI - Distribution of mRNA for CCK-B receptor in the brain of Mastomys natalensis: abundant expression in telencephalic neurons. AB - The distribution of cholecystokinin B (CCK-B) receptors in the Mastomys brain was studied using Northern blot analysis and in situ hybridization technique. By Northern blot analysis using 32P-labeled cDNA probe, the cortex had the highest hybridization signal of CCK-B receptor mRNA in the brain. The olfactory bulb and hippocampus showed a moderate level of signals. In situ hybridization using 35S labeled cRNA probes revealed a wide and region-specific distribution of CCK-B receptor mRNA in the telencephalon. Throughout the cerebral cortex, labeled cells were found in all layers, with higher intensities in layers II, V and VI. Pyramidal cells of the layer II of the piriform cortex showed the highest level of signals in the brain. In the hippocampus, most of the pyramidal cells of the Ammon's horn were labeled, although labeled cells were not detected in other layers. Distinct signals were also detected in the various amygdaloid nuclei, caudate-putamen, reticular thalamic nucleus, hypothalamic ventromedial nucleus and inferior colliculus. This distribution pattern may further support the prominent existence of CCK-B receptors in the brain particularly in the telencephalon. PMID- 8004468 TI - Dilatation of cerebral arterioles in response to N-methyl-D-aspartate: role of CGRP and acetylcholine. AB - The purpose of these experiments was to examine mechanisms by which N-methyl-D aspartate (NMDA) produces nitric oxide-dependent vasodilatation in brain. Some nitrovasodilators appear to dilate cerebral arterioles, in part, by release of calcitonin gene-related peptide (CGRP) from trigeminal fibers. The first goal of this study was to examine the hypothesis that dilatation of cerebral arterioles in response to NMDA is mediated by activation of receptors for CGRP. Diameters of cerebral arterioles were measured using a closed cranial window in anesthetized rabbits. Topical CGRP (1 and 10 nM) dilated cerebral arterioles by 30 +/- 9 (mean +/- S.E.M.) and 72 +/- 9%, respectively, from a control diameter of 94 +/- 7 microns. This response was inhibited almost completely by the CGRP antagonist CGRP(8-37) (0.5 microM). NMDA (100 and 300 microM) dilated cerebral arterioles by 14 +/- 5 and 38 +/- 7% in the absence and 20 +/- 5% and 30 +/- 6% in the presence, respectively, of CGRP(8-37). Neurons may release acetylcholine in response to activation with NMDA. The second goal of the present study was to examine the hypothesis that dilatation of cerebral arterioles in response to NMDA is mediated by acetylcholine. Topical atropine (2 micrograms/ml) completely inhibited dilatation of cerebral arterioles in response to acetylcholine, but had no effect on vasodilatation in response to NMDA. Thus, vasodilatation of cerebral arterioles in response to NMDA does not appear to be dependent on activation of receptors for CGRP or acetylcholine. PMID- 8004469 TI - Endothelial differentiation in intracerebral and subcutaneous experimental gliomas. AB - Blood-brain barrier (BBB) properties of endothelial cells have on impact on brain tumor behavior, diagnosis, and response to therapy. Biochemical BBB properties are expressed by endothelial cells within intracerebral (IC) gliomas but little is known regarding the expression of BBB-associated proteins within gliomas established subcutaneously (SC), a site that is frequently used in experimental glioma models. We compared the expression of two BBB proteins, glucose transporter type-1 (Glut1) and endothelial barrier antigen (EBA), in IC and SC rat 9L and F98 gliomas. The percentage of microvessels with immunohistochemically detectable Glut1 and EBA in IC 9L tumors (31-98%) contrasted with that found in SC 9L tumors (0-3.9%) (P < 0.0001). Likewise, the percentage of immunohistochemically-positive vessels in IC F98 tumors (35-66%) differed markedly from that in SC F98 tumors (0%) (P < 0.0001). These differences were not explained by effects of tumor location on vessel density or tumor histology. These findings demonstrate that the peritumoral environment influences endothelial differentiation within glial tumors and suggest that glioma cells maintain but do not induce the expression of barrier properties in vessels that infiltrate tumor from surrounding tissue. PMID- 8004470 TI - [Is fish oil supplementation (n-3 fatty acids) important for the diabetic?]. AB - Since the 70-ties many investigators have studied the effects of fish oil supplementation in experimental and clinical medicine. Regarding to some perspective results (in healthy subjects, cardiovascular, autoimmune diseases, in disorders of lipid metabolism, in carcinogenesis a.o.), there were also expected favourable consequences in diabetic subjects. Taking into consideration the most controversial information in this field, the authors in this review article try to summarize all relevant questions. (Fig. 1, Tab. 1, Ref. 22.) PMID- 8004471 TI - [Dynamics of digoxin-like immunoactivity during the oral glucose tolerance test in pregnant women]. AB - The changes of serum digoxin-like immunoactivity (DLIA) during 75g oral glucose tolerance test (OGTT), were investigated in 25 pregnant women with various glucose tolerance. 13 women had a normal glucose tolerance (NGT), 12 women had an impaired glucose tolerance (IGT) or gestational diabetes mellitus (GDM). Test was performed after 25 week of pregnancy. The results were compared with 9 nonpregnant healthy volunteers (NHV). After an oral glucose challenge, there was observed a significant decrease in serum DLIA (p < 0.01 in 1st hour), in both groups of the pregnant women. In the group of NHV these findings were not found. Our findings suggest a possible relationships between DLIA and glucose tolerance in pregnant women. However, it needs further investigation. (Tab. 1, Fig. 1, Ref. 24.) PMID- 8004472 TI - [Nitrates and nitrites in gastric juice in chronic gastritis]. AB - Atrophic gastritis is precancerous condition of the intestinal type of gastric carcinoma. This process supposes a genotoxic effect of N-nitroso-compounds which are formed in the stomach by nitrosation of nitrites and organic nitrogen compounds. The authors examined 41 patients with chronic superficial and atrophic gastritis. They examined the pH and concentration of nitrates and nitrites in gastric juice taken in the morning before meal. They discovered that in severe atrophic gastritis the amount of nitrates is significantly increased and the amount of nitrites is decreased, all in comparison with superficial gastritis. An exponential relation of the concentration of nitrites towards the pH of gastric juice was found to be NO2- = epH-6.5, CC = 0.935. A significant elevation of nitrite concentration was observed in cases of pH being higher than 5.5. Nitrate concentration altered in dependence of the value of gastric pH. Oral administration of 300 mg of vitamin C or 250 mg of vitamin E did not significantly affect the amount of gastric nitrites. The work discusses the mutual relation of nitrites, ascorbic acid and alpha-tocopherol towards the formation of N-nitroso-compounds in the stomach inflicted by atrophic gastritis. (Tab. 3, Fig. 2, Ref. 25.) PMID- 8004473 TI - [Atypically localized scrofuloderma]. AB - Tuberculosis of the skin and peripheral subcutaneous lymphnodes represents the most frequent forms of extrapulmonary tuberculosis. The group of patients subjected to our observation had the highest incidence of tuberculous lymphadenitis. The second most frequent disease observed was scrofuloderma. Its profound colliquative form, the so-called tuberculosis subcutanea fistulosa profunda is extremely scarce. Our work describes one case of such a disease. The pathological process in our patient was localized in the perianal and perigenital region. Especially this localization is typical for other non-specific dermal diseases. The work stresses the tuberculous ethiology of the pathological process in this region from the differential diagnostic point of view. The fact that this disease has not been appropriately treated due to the lack of precedent cases during the past years, has caused long lasting physical and psychical suffering of the patient. (Tab. 1, Fig. 1, Ref. 5.) PMID- 8004474 TI - [Architectonics of pulmonary vessels in pulmonary stenosis]. AB - The authors aimed their work on the study of the architecture of pulmonary blood vessels and blood flow via pulmonary vascular network in patients with Fallot malformation. In 34 children with valvular stenosis of a. pulmonalis and in 12 children with Fallot tetralogy they analysed in detail their angiograms, paying attention to evaluation of the architecture of truncus pulmonalis and its branches, the discharging part of the right ventricle, and the state of the arterial phase of the pulmonary vascular network. On the basis of their results the authors explain the preferential blood distribution in Fallot's tetralogy by the displacement of the outflow part of the right ventricle to the right and by a greater amanation angle between the right branch of a.pulmonalis and its truncus. Better routing of blood into the left lung in patients with pulmonary valvular stenosis is according to the authors due to a greater emanation angle between the left branch of a.pulmonaris and its truncus. The authors analyse also the mechanism of formation of poststenotic dilatation of truncus pulmonaris and the left branch of a.pulmonaris in cases of valvular stenosis in infant age. (Fig. 4, Ref. 12.) PMID- 8004475 TI - [Vitiligo--an enigmatic disease. I. Epidemiology, etiopathogenesis and clinical findings]. PMID- 8004476 TI - [Stereotaxic biopsy of brain tumors]. AB - The work re-evaluates the meaning of stereotactic bioptic examination in 50 neurosurgical patients. Bioptic material gained for histologic purposes does not secure always the achievement of the correct histologic diagnosis. The authors critically reevaluate the possibilities of this diagnostic method. They do not consider as adequate to claim multiple expansive processes to be inoperable, respectively as being refractory towards therapy, when the histologic conclusion is lacking. In cases of inconsistency in histologic conclusions from two neuropathologists the further fate of the patient is conditioned by the neuropathologist's stand-point, but also by the clinical experience of the neurosurgeon who overtakes the final responsibility for the patient's further fate. Recently available methods (CT,MR, spectrography) are diagnostically not so precise as to be able to manage without stereotactic biopsy. (Tab. 3, Fig. 5, Ref. 10.). PMID- 8004477 TI - [Massive hemorrhage from duodenal adenocarcinoma]. AB - The authors report the case of a 48 year old patient with duodenal adenocarcinoma. The patient was hospitalized at the internal clinic and due to massive bleeding into GIT was removed into the surgical clinic in a state of shock. The operation revealed a Tu formation on the border between D3 and D4, and a palliative resection was performed. The histologic examination verified the diagnosis of the duodenal carcinoma, WHO gr.II. During the postoperative period the patient received 4 chemotherapeutic treatments, although literature generally refers to chemotherapy as having no effect on the time of survival in patients with duodenal adenocarcinoma. The authors conclude that in patients with a long termed history of atypical abdominal symptoms including bleeding into GIT which are inexplicable owing to fibroscopy and x-ray, it is necessary to take into consideration the possible presence of neoplasms in the small intestine, and hence in the duodenum. In cases with massive bleeding they recommend palliative resection and subsequent chemotherapy. (Fig. 6, Ref. 11.). PMID- 8004478 TI - [The effect of antibiotics and their combinations on Pseudomonas aeruginosa in vitro]. AB - During the ten year period (1981-1990) of detection of Pseudomonas aeruginosa susceptibility towards anti-Pseudomonas antibiotics a decrease in susceptibility towards GEN took place, namely from 91.7% to 80.0%. Susceptibility towards STR, COL and POL has not altered. During the course of five years we recorded a remarkable augmentation in resistance towards the group of 10 new antibiotics NET by 24.3%, TIC-by 20.6% and AZL-by 18.5%. The most effective antibiotics of this group were CIP (100%), AMI (98.6%), OFL (99.3%), and CTZ (100%). Eight combinations of antibiotics were tested on 100 strains and CTX+GEN was proved to be the most effective combination-synergistic effect on 92.0 strains. The comparison of the effect of CTX+GEN combination on 12 strains implies identical results gained by both, the plate dilution method and the method of detection of lethal effect rate. For the purpose of routinized examinations the dilution micromethod is the most suitable. (Tab. 4, Ref. 19.). PMID- 8004479 TI - [Biochemical parameters in the blood of patients during open-heart surgery. I. Monitoring changes in energy metabolism]. AB - Levels of lactate, inorganic phosphate and uric acid in arterial, mixed venous and coronary sinus blood were studied in patients during open-heart surgery. It was found that the determination of mentioned biochemical parameters can provide information regarding the energetic metabolism status of the whole organism, but selectively, also of the patient's myocardium. The results of biochemical analyses demonstrate a significant loading of the organism manifested by metabolic alterations, especially after long-term cardiopulmonary bypass. The study of mentioned biochemical parameters can be employed for investigation of a more efficient protection of myocardium against ischemia-reperfusion injury. (Fig. 6, Ref. 18). PMID- 8004480 TI - Determination of galactose elimination capacity after intravenous administration in patients with chronic liver diseases. AB - The authors describe a simple method of examination of galactose elimination capacity after intravenous administration of a twenty per cent solution in the total dose of 0.5 g galactose/kg body weight. After enzymatic determination of galactose concentration in six samples of venous blood (taken within 25, 30, 35, 40, 45 and 50 minutes after finishing the galactose infusion) the elimination curve of galactose and the intersection point with the time axis (t) is assessed and the galactose elimination capacity is calculated. In patients with liver steatosis and steatofibrosis, chronic hepatitis and liver cirrhosis the mean values of galactose elimination capacity were significantly lower in comparison with healthy volunteers. The method is sufficiently reliable, precise and quickly performable. It is suitable for evaluation and monitoring of the functional liver capacity, severity and progression rate of liver diseases. (Tab. 1. Fig. 2. Ref. 28). PMID- 8004481 TI - The development of lipid metabolism. Changes in the level of fatty acids in serum during postnatal ontogenesis in the rat. AB - In young rats of 5 different age groups the spectrum (per cent) of 6 FFA was determined. The results show, that palmitic acid (C16:0) represents the main FFA in all age groups; at the end of the first week forms nearly 50 per cent. In adult animals (8-week-old) values decreased to 26 per cent. Similarly, the myristic acid (C14:0) was found highest in suckling animals (10 per cent) and decreased with age. The ratio of saturated to unsaturated FA (S/U) decreased with age. In other animals of 7 different age groups the concentration of total and of individual FFA was investigated. The results were expressed in nmol.l-1. Results showed, that the total concentration of FFA during the first postnatal month is nearly 2-times higher than in adults. The ratio of S/U FFA decreased from 1.81 to 0.85. The concentrations of individual FFA showed different age-dependent trend. Myristic and stearic acids (C14:0 and 18:0) increased with age till the 4th week. The concentrations of palmitic, oleic and linoleic acids were high during the first 3 weeks of age and decreased after weaning. The concentration of palmitate oleic acid (C16:1) was lowest in all age groups as well as that of palmitic (C 16:0) was always the highest. These results show, that changes in concentration of individual FFA with age are not dependent only on the intake of the milk. (Tab. 3, Fig. 1, Ref. 8). PMID- 8004482 TI - [Gamma-aminobutyric acid and glutamate decarboxylase]. AB - Gamma-aminobutyric acid (GABA) is the main inhibitory neurotransmitter in the CNS, taking part in processes which are now relatively well understood but also in processes which are remarkable progress has been achieved. The most thoroughly studied field of GABA operation is its role of inhibitory neurotransmitter realized through the mediation of GABA-A and GABA-B receptors. There are at least 40 per cent of synaptic inhibitory events in the CNS in which the neurotransmitter action of GABA is involved. The action of GABA on GABA-A receptor, a Cl- channel, is influenced by benzodiazepines, barbiturates and other substances, suggesting that some neurological and psychiatric diseases are connected with the function of GABA-A receptor. In addition to synaptic inhibition, GABA has several metabolic regulatory functions. GABA is produced not only in neurons but also in beta cells of the pancreas and in tubular cells of the kidney cortex. Its role in these parenchymatous cells is not sufficiently understood. Similarly as GABA, glutamic acid decarboxylase (GAD), an enzyme catalysing GABA formation from glutamate, has also been intensively studied. GAD structure, its function in various parts of the CNS and in some parenchymatous cells, and the regulation of GAD activity are still in the focus of interest. Recently GAD has been demonstrated to act as autoantigen in the rare neurological disease "stiff man syndrome" (SMS) and in insulin-dependent diabetes mellitus (IDDM). In the presented paper a short review of GABA functions, GAD properties and of the antigenic feature of GAD are given. (Fig. 7, Ref. 41.) PMID- 8004483 TI - Levels of selected elements (Fe, As, Cd, Pb, Zn, Mn) in biological samples from ferrochromium workers. AB - A long-term exposure to metals poses the question of whether the impaired health condition is caused exclusively by the quantitatively dominant exposure metal. In 67 workers exposed to ferrochromium alloys on average 12.5 +/- 1.09 years (mean +/- SE), the subgroups of ferrochromium workers and operators of dust removing equipment, average Cr values in urine were 0.233 +/- 0.032 mumol.l-1 (mean +/- SE). In the control group (K) the average Cr values were 0.034 +/- 0.004 mumol.l 1 of urine (mean +/- SE). The levels of plasmatic Fe were assessed photometrically; the levels of Fe, As, Cd, Pb, Mn and Zn in hair, urine and blood were assessed by atom-absorption spectrophotometry (Varian). The results were compared with the control group not significantly different in age (t-test). All the values were correlated with age, years of exposure and the number of cigarettes smoked during life. The values of the single selected metals in furnace workers and operators of dust removing devices were not higher than the limits set for the groups of workers exposed to metals. But compared to the original biological background, there was observed a significant Cd increase (hair, blood, urine) year by year. Average values of As, Pb, Fe, and Mn in hair of the exposed workers were also higher compared to the group K. As and Mn values in hair were increasing up with the years of exposure (r = 0.465, p < 0.05; r = 0.580, p < 0.001). No expected higher values of plasmatic Fe were found. Zn values in hair were falling down with the years of exposure as well as with age, in all groups including the group K. The authors discuss the possible causes of the quantitative changes in the selected metals in connection with professional exposure and non-professional effects (especially smoking). Higher cancer incidence of the organs affected has not been observed so far in the study plant. (Tab. 2, Fig. 8, Ref. 41.) PMID- 8004484 TI - [Results of radionuclide ventriculography and correlation with echocardiography and angiography]. AB - In a group of 24 patients with coronary artery diseases, correlations of left ventricle end-diastolic volume (EDV), end-systolic volume (ESV), systolic volume (SV), and ejection fraction (EF) measurement results were assessed. Compared results were obtained with radiological angiography (RTG), echocardiography (USG), and radionuclide ventriculography (RNVG). In RNVG, the left ventricle volume was calculated using a geometrical method (GEO), a sample method with measurement of left ventricle position depth from a scintigraphic image (VZ1), and a sample method with assessment of left ventricle position depth from body height and body weight (VZ2). Interpersonal variability of RNVG evaluation was assessed simultaneously. Compared with RTG, the best correlation of EDV measurement was attained with GEO (r = 0.83) and VZ2 (r = 0.82). These methods correlate best also in ESV measurement (r = 0.91). The best correlation of EF values was obtained with USG, while r = 0.85 when using GEO and VZ2. A very low correlation was found in SV (r values from 0.39 to 0.50). The studied methods usually overestimate low values and underestimate higher values. To the EF value of 50 per cent corresponds in USG the value 48 per cent, in GEO and VZ2 the value 42 per cent. The values of EDV, ESV, and SV obtained with USG and RNVG correlate well with RTG, while the values of SV are, due to a low correlation, practically useless. Interpersonal variability of RNVG methods evaluation is minimal. (Tab. 6, Ref. 30.) PMID- 8004485 TI - [Intestinal parasites in secondary school students in the Martin District]. AB - The authors report on the prevalence of intestinal parasites in 1763 students of selected secondary schools in District Martin from 1988 to 1990 as continuation of parasitologic surveillance of pre-school children collectives and of elementary school pupils. The situation in occurrence of geohelminthiasis in the investigated group of students is considered to be very favorable and could reflect, in some degree, the parasitologic surveillance and treatment of positive cases in the seventies. The prevalence of intestinal protozoa, especially Giardia intestinalis, is in examined students only a little lower as the values given by our authors for population of children. This indicates a shift of epidemiologic importance from geohelminthiases towards the protozoal infections. (Tab. 5, Ref. 18). PMID- 8004486 TI - [Thrombolytic therapy of acute myocardial infarct]. AB - In the period of two years the authors treated at the coronary care unit 146 patients inflicted by the acute myocardial infarction (AMI). In 15 of them (13 men, 2 women, 13 times Q and twice non-Q, 5 times anterior, 10 times inferior) they performed intravenous thrombolytic treatment by use of streptokinase. The success rate of the thrombolytic therapy was evaluated by noninvasive markers: 1.) rapid withdrawal of chest pain, 2.) rapid (in 6 hours) and essential improvement of ST segment elevation and 3.) presence of reperfusion arrhythmias (in 6 hours). The authors detected insufficient medicinal conciousness among their health district population as regard to their response after the AMI origin (absolute majority of patients delayed their arrival). Minor complications due to therapy (allergy and minor local hemorrhage) occurred in 4 patients. Nobody died. Only those cases were considered as being successful, in which all three success rate markers were present. This condition was fulfilled in 8 patients (i.e. in 53% of cases) and with minor insufficiencies in further two patients (which would increase the percentage of the success rate to 67%). This success rate of the thrombolytic therapy ranges within the limits given by literature. In five patients the authors evaluated the behaviour of the left ventricular asynergy (its range and index) prior to and following the thrombolytic therapy and this examination they consider to be appropriate for observance of the thrombolytic therapy success rate in patients with AMI. (Tab. 3, Ref. 20.). PMID- 8004487 TI - [Late postoperative complications after primary treatment of aortic coarctation]. AB - During the period between 1963 and 1988, 343 patients were operated due to aortic coarctation. 14 patients (4%) were necessarily reoperated for late postoperative complications. In 3 cases (0.8%) reoperation was indicated due to the development of aneurysm in the region of primary operation of aortic coarctation. The development of aneurysm is prevalently predisposed by Vosschulte's indirect aortoplastic operation by the use of a synthetic patch. In the remaining 11 patients (3.2%) the reoperation was indicated owing to the development of recoarctation. Today recoarctation concerns children which were operated under the age of two. The most important moment favourable for the recoarctation development is the secondary constriction of the repaired region in consequence of the coarctation listel fibroid tissue and owing to the incapability of the anastomosis to grow. The perspective rests on using new suture material and combined techniques. Late postoperative complications which follow operations performed due to aorta coarctation remarkably augment the peri and postoperative mortality. Three cases out of the given group of 14 patients terminated by exitus (21%). Hence, it is necessary to remove all moments of predisposition creating a condition favourable for the development of recoarctation and aneurysm. (Tab 2, Fig. 1, Ref. 14.). PMID- 8004488 TI - [Clinical and serologic study of Czecho-Slovak citizens working in developing countries from the aspect of risk of infection with Coxiella burnetii]. AB - In the years 1984-1988 we observed, besides the routine examinations of history, clinical state, and laboratory tests, also the presence of antibodies to Coxiella burnetii antigens by means of microagglutination reaction (MAR). The examinations were performed in our citizens returning to Czecho-Slovakia from a long termed business stay in the developing countries. Antibodies to C. burnetii antigen 2 have been detected entirely in 91 serum samples, out of which 48 cases following their stay in Libya, 42 cases following their stay in Iraq, and 1 in Syria. Diagnostically significant antibody titres (64) were detected in 44 serum samples, in which the serological positivity was proved by complement fixation test (CFT) examination. Clinical symptoms in the history, responding to the acute form of "Q" fever, occurred in 44 serologically positive cases, 37 of which developed high antibody titres, which is considered to be a significantly high incidence. The results imply the necessity to become more concerned by the incidence of "Q" fever, its diagnostics and therapy, eventually prevention in our citizens working in a more exacting climate of some developing countries. (Tab. 1, Ref. 15.). PMID- 8004489 TI - Free radicals derived from oxygen, and medicine. AB - Toxic free radicals may be produced by many reactions, which are necessary for the maintenance of normal metabolism, and the production of energy in cells. The origin, reactivity with other molecules and removal of free radicals, is in the foreground of interest since their effect is mostly toxic and result in a whole series of pathological states of cells, organs and whole organisms. Production of these radicals increases in oxidative stress and in the presence of ions of metals (chiefly iron), leads to the creation of more reactive metabolites. The generally accepted view is that the main biological actor in damaged tissues is the hydroxyl radical (OH), which is created in the iron catalyzed Haber-Weiss reaction. The balance between the increased creation of free radicals in various pathological states, or unfavourable conditions in the environment, and natural antioxidants of a low-molecular (vitamin C, E, glutathione etc.) or enzyme character (superoxide dismutase, glutathione peroxidase, glutathione reductase, catalase, etc.), plays the chief role in damage which is the cause of many diseases and ageing. (Fig. 3, Tab. 5, Ref. 62.). PMID- 8004490 TI - [Electrostimulation of the urinary bladder]. AB - The authors present their first results with urinary bladder stimulation in dogs by using an electronic stimulator and electrodes of their own construction. Neurostimulation was carried out by means of contactless application of electrical rectangular pulses with the voltage ranging from 1 to 10 volts, frequency from 10 to 300 Hz and pulse with 1 ms. Due to the stimulation of the branches of the pelvis plexus an isolated contraction of the bladder detrussor with an increase of intravesical pressure up to 65 cm H2O was observed with subsequent spontaneous voiding. The stimulation of the intact sacral root S2 led to detrussor-sphincteric dyssynergia caused by simultaneous contraction of the detrussor and the striated urethral sphincter. The poststimulus spurt of urine was observed at the end of each S2 stimulation. The authors inform about the further plan of experimental work before introducing the method into clinical practice. (Fig. 4, Ref. 17.). PMID- 8004491 TI - [Glutamic acid decarboxylase in the brain, pancreas and kidneys. Comparison of its properties]. AB - Comparisons of soluble and bound GAD activities in brain, pancreas, and kidneys were performed. In all three organs GAD was present in three forms: soluble GAD; GAD, the solubility of which was achievable by means of CHAPS detergent; and GAD, refractory towards the detergent affect. The activity of these three GAD fractions, each belonging to a different cellular compartment, proportionally differed. The ratio of free, bound, and irreversibly bound activity expressed in percentage was 63:21:15 in the brain, and 14:40:36 in the pancreas. In coincidence with the occurrence of autoantibodies to GAD from the brain under the condition of SMS, and that from the pancreatic beta-cells under the condition of IDDM, it is supposed that the conditions favourable for the origin of the immune response are rendered by GAD bound in membranes. In kidneys the proportions of free (15%) and bound GAD (29%) are complicated by until now unassessed factors, since their isolation from the free, eventually bound GAD causes an activity waste of 50% which supervenes following the homogenate separation by the use of centrifuge. Effect of ATP and chlorides displays both, different and common properties of GAD from the mentioned three organs. ATP inhibited the brain GAD and the renal supernatant GAD, whereas it activated GAD from the homogenate and sediment of the kidneys and the pancreatic GAD. Chlorides inhibited the brain and pancreatic GAD and activated the renal GAD. (Fig. 8, Tab. 1, Ref. 16.). PMID- 8004492 TI - [The effect of Staphylococcus aureus vaccine on professional phagocytes in vitro and in vivo]. AB - Effect of Staphylococcus aureus vaccine on metabolic and functional activities of polymorphonuclear leucocytes and guinea pig macrophages was observed. The tested vaccine following a short contact with human polymorphonuclear leucocytes isolated from peripheral blood inhibited candidacidal and phagocytic activities, whereas the phagocytic index stayed unchanged. The tested vaccine stimulated the INT-reductase activity and superoxide production, as well as extracellular liberation of lysosome enzymes from polymorphonuclear leucocytes. Application of the Staphylococcus aureus vaccine to guinea pigs 35, 30, 28, and 23 days prior to the acquirement of peritoneal macrophages, augmented, as compared to the control group, the amount of peritoneal macrophages and their phagocytic activity. Candidacidal and metabolic activities stayed unchanged. The results imply that the contact of phagocytic cells with the antigen, affects their biochemical and functional activities. Activities are dependent of the length of the period during which the antigen stimulation takes place, and of its quantity. Examination of phagocytes can be recommended for adjustment of both, vaccine doses and intervals between their individual applications. (Tab. 5, Ref. 19.). PMID- 8004493 TI - [Nasal reactivity in anesthetized guinea pigs]. AB - The authors elaborated a methodical procedure for observing the nasal reactivity in anaesthetized guinea pigs (Pentobarbital Spofa, 32 mg.kg-1 i.p.): Volume changes of the nasal mucosa were estimated from the changes in nasal airflow resistance (Rn). Via tracheostomic aperture the authors introduced a cannula into the nasopharynx. By the use of the cannula they drove doses of continual airflow through the nasal cavities, the airflow doses being 0.5, 1.0, 1.5, thereafter in reversed order: 1.0 and 0.5 l.min-1. Contemporaneously they registered the nasopharyngeal pressure. Rn represented the quotient of the transnasal pressure (the difference between the nasopharyngeal and atmospheric pressure) and the relevant airflow. They filled the nasal cavities for three minutes with histamine solution, the concentration of which was doubled following each application, gradually from 0.625 to 2.0 g.l-1. They discovered that the average values of Rn increase in dependence of histamine doses. Maximal response of the nasal mucosa was detected in between the doses of 0.5-1.0 g.l-1. For estimation of the threshold dose it is necessary to observe still lower histamine concentrations. (Fig. 1, Ref. 14.). PMID- 8004495 TI - [Society of Slovak Physicians in Bratislava]. PMID- 8004494 TI - [Correlation of urography, ultrasonography and computer tomography with clinical findings in examinations of the kidneys and retroperitoneum. Possibilities of diagnostic errors]. AB - The authors prospectively and retrospectively mutually compared the diagnostic value of urography, ultrasonography (USG), and computer tomography (CT) in four patients, with the diagnosis misstated prior to operation. The most valuable findings were provided by CT. Mere utilization of these methods does not exclude the possibility of diagnostic misstatements. In three patients the ultimate diagnosis was assessed on the basis of operative revision and in one patient, by means of cytologic examination of the renal punctate. Owing to retrospective evaluation of examinations, diagnostically valuable symptoms which could have lead to the correct diagnosis, were distinguished. Hence, examinations must necessarily be evaluated in complex with the general clinical state. (Fig. 6, Ref. 14.). PMID- 8004496 TI - [Mitochondrial diseases]. AB - In this review the author describes the current knowledge about mitochondrial diseases (mitochondrial myopathies, mitochondrial encephalomyopathies and mitochondrial cardiomyopathies) in both clinical and experimental medicine. This description concerns historical development of mitochondrial diseases, biochemical alterations and genetic disturbances of damaged mitochondria. Also it shows some mechanisms deletion of mitochondria, first diagnostic possibilities concerning mitochondrial diseases in clinical medicine and their response to therapy. (Ref. 105.). PMID- 8004497 TI - [Non-invasive assessment of the efficacy of long-term vasodilator therapy of cardiac decompensation in patients with dilated cardiomyopathy]. AB - In 18 patients (14 men, 4 women, in the age of 37-52 years, mean = 43 years) with dilated cardiomyopathy allocated into NYHA functional classification groups III IV, the efficacy of ambulatory long term (mean = 6 years) vasodilator therapy by means of non-invasive methods was evaluated. NITRO-MACK retard (venodilator) in the dosage of 20 mg per day and DIHYDRALAZIN (arteriodilator) in the dosage of 100-200 mg per day were combined simultaneously with continuous administration of cardiotonics and diuretics. Vasodilator therapy had a favourable effect on systolic and diastolic function of the left ventricle with the mostly marked effect at the beginning of treatment. Amidst non-invasive parameters, the diastolic amplitude time index and left ventricular hypertrophy-dilatation index had the greatest prognostic value regarding the treatment efficacy and survival of patients. This objective evidence of the efficacy of vasodilator therapy in patients with dilated cardiomyopathy coincided with the improvement of clinical status, subjective relief, moderation of decompensation, and thus with the improvement of life quality. (Fig. 1, Tab. 4, Ref. 24.). PMID- 8004498 TI - [Treatment of fractures of the upper cervical spine (C1 and C2)]. AB - The authors provide a review of current opinions on the treatment of fractures in the region of C1 and C2. It is necessary to take the possibility of this localization of fractures into consideration in polytraumatized patients, in those unconscious, and in cases of algesia in the cervical region. A significant post in diagnostics belongs to CT examination which reveals the extent and type of fracture and the degree of dislocation. The authors refer to the classification of Aebi and Nazarian which should be accepted in spondylo-surgical practice. The authors recommend conservative therapy of atlas fractures, preferably by the use of Halo-apparatuses. The direct osteosynthesis by means of two compressible screws according to Bohler/Magerl represents the method of choice in treating dens fractures. The surgical modification utilizing a small T splint was proved competent in fractures interfering the vertebral corpus (type III). Fractures of isthmus with no dislocation are recommended to be treated conservatively by the use of Halo-fixation, in cases with dislocation (types E II, E III) they consider the method of intercorporal desis C 2/3 according to Decaulx and modified by Caspar, to be optimal. (Fig. 8, Ref. 20.). PMID- 8004499 TI - [Erectile dysfunctions in patients treated with hemodialysis and kidney transplantation]. AB - The incidence of erectile dysfunction in patients suffering from severe renal diseases in the stage of renal insufficiency is significantly higher in comparison with healthy men of the same age. In the etiopathogenesis of erectile disorders, both organic and psychogenic factors participate in combination. By means of a questionnaire, the authors have collected information from 53 men treated by hemodialysis and kidney transplantation because of renal failure. Erectile disorders occurred in 41.5 per cent of men with chronic renal insufficiency. On one side hemodialysis improved the erectile dysfunction in two patients, in total, however, the incidence of impotence increased to 64.2 per cent. Erectile dysfunction was reported by 71.7 per cent of patients after kidney transplantation. The authors describe two cases of iatrogenic arterial insufficiency of the penis as the cause of impotence after secondary renal transplantation. In uremic patients as possible therapeutic methods, intracavernous application of vasoactive drugs or penile prostheses implantation should be considered. (Fig. 2, Ref. 20). PMID- 8004500 TI - [The role of the neurosurgeon in histopathologic diagnosis]. AB - Neurosurgical practice has proved that the establishment of a correct neurohistopathologic diagnosis is sometimes difficult. Inconsistency of diagnoses resulting from unbiased examinations of several neuropathologists is not uncommon. The authors-neurosurgeons-have performed 300 fast neurohistopathologic examinations by means of smear technique. Correct diagnosis was stated in more than 90% of cases. Bioptic examination may represent a contribution in cases where postoperative irradiation is indicated, namely under diagnostically controversial circumstances. The authors re-evaluate the possibilities of utilization of smear technique for the purpose of histopathologic diagnostics performed directly by neurosurgeons. (Tab. 7, Ref. 5.). PMID- 8004501 TI - [Functional status of thrombocytes in men and women in younger age groups]. AB - Differences in the functional status of platelets in vitro were compared between young adult men and women. Platelets in women were found to have a higher susceptibility to ADP, epinephrine, arachidonic acid and to produce more TXB2. These changes appear to be due to the declined hematocrit and thus to lower concentrations of sodium citrate, a commonly used anticoagulant. Platelet activity was conversely related to plasma sodium citrate. Since calcium chloride was found to offset the inhibitory effect of sodium citrate, it was assumed that the sex-related differences observed in platelet activity were due to varied levels of ionized calcium. The platelet activity was at equal values of hematocrit equal in both sexes. (Tab. 3, Ref. 19.). PMID- 8004502 TI - [Tuberculous lymphadenitis--the most frequent symptom of extra-pulmonary tuberculosis]. AB - The work reports about the recently detected forms of tbc of skin and peripheral lymphnodes, which were confirmed in patients of the Dermatology Department of UTaRCH, Bratislava, Podunajske Biskupice in the period 1981-1989. From the total of 221 newly detected diseases the lymphadenitis or tbc cutis colliquativa occurred in 171 patients (77.4%). The lymphadenitis was confirmed in 140 patients (63.4%). Lymphadenitis, or scrofuloderma (tbc cutis colliquativa) most frequently inflicted the cervical subcutaneous lymphnodes--in 140 patients (81.9%). Unilateral infliction of lymphnodes prevailed. Incidence of these diseases was significantly higher in women (76%) than in men (24%). Within the process of differential diagnostics, in cases with inflicted peripheral subcutaneous lymphnodes it is necessary to take into consideration the possibility of their tuberculous etiology. (Fig. 1, Tab. 3, Ref. 7.). PMID- 8004503 TI - [The role of platelet activating factor in the pathogenesis of asthma]. AB - The work reviews knowledge about the function of PAF, the presupposed mediator of asthma. The PAF mediator evokes contraction of smooth muscles of respiratory passages, too in vivo as in vitro, by means of an indirect mechanism involving activated platelets which function as intermediaries. The constrictor released due to this process can be represented by histamine or a product of arachidonic acid. Mucous secretion is according to current knowledge stimulated by PAF. The PAF mediator appears to be a considerable chemotactic factor for eosinophils which by their cytotoxic effects on respiratory epithelium support the origin and development of bronchial hyperresponsiveness. PAF has an eminent effect on the growth of microvascular permeability. Antagonists of PAF inhibit some mentioned PAF effects. Their possible therapeutic utilization, excluding ketotiphen, are currently subjected to research. (Fig. 2, Ref. 17.). PMID- 8004504 TI - [Intra-articular and peri-articular injection therapy]. AB - The author in the article in the form of an assembled report deals with the problem of intraarticular and periarticular injection therapy. The author divides the matter in two parts, the diagnostics and therapy. In general, there are four possibilities of influencing the joint by means of an injection. First, the evacuation of intraarticular contents, second, the introducing of pharmacy into the joint, third, the mechanical irritation of certain connective tissue structures of the joint which ought to evoke the formation of a scar, and fourth, the mechanical stabilization of the structure inflicted by lesion. Owing to the removal of pain, the negative effects of neuromuscular reflexes due to algesic stimuli, are eliminated. There are two basic types of affections subjectable to injection intraarticular treatment, namely the diseases coinciding with the damage of articular biomechanics, particularly disturbances of both, the sliding in arthrosis and articular stability. In such cases the application of chondroprotectives, eventually formation of a scar by irritation of the appropriate connective tissue structures, decreasing of instability and removal of contractures are theoretically justified. Evacuation punction is indicated in post-traumatic states, inflammatory states indicate diagnostic punction, and aseptic inflammation requires infiltration of pharmacy with antiphlogistic effect. Injection intrarticular intervention represents a justified diagnostic procedure and an effective therapeutical administration. It is necessary to become familiar with the topographic anatomy of joints, just as with the technique of application, contraindications, and determination of possible limitations of intraarticular treatment and surgical reconstructive intervention into the joint or extremity. The most serious complications of intraarticular injection administration are represented by iatrogenic infections and cortisone like arthropathies.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8004506 TI - Technology and restructuring: is Captain Kirk out to get your job? PMID- 8004505 TI - Promoting the value of nursing to the public. PMID- 8004507 TI - UCSF AIDS research RNs protest layoffs. PMID- 8004508 TI - Secrets. PMID- 8004509 TI - AIDS and dentistry. PMID- 8004510 TI - Patient education and case acceptance. PMID- 8004511 TI - Dental fees. PMID- 8004512 TI - The guiding lights. PMID- 8004514 TI - High stress-related claims hurt everyone. PMID- 8004513 TI - Calling all seniors: how to meet the needs of geriatric patients. PMID- 8004515 TI - Dr. Saul Kamen: a 50 year odyssey through geriatric dentistry. Interview by P. Ralph Crawford. PMID- 8004516 TI - Dentistry for the nursing home resident: how to begin or improve your oral health care program. AB - This paper identifies the steps a general practitioner should follow to initiate or improve an oral health-care program in a nursing facility. The areas to be considered in the planning stages are explored, as well as the types of services that may be performed and the fees that the practitioner should charge. The paper provides a general overview of nursing home oral-dental services. Problems, a solution, a total quality management process for initiating the services, some questions that practitioners will need to ask and answer themselves, and a plan of action are discussed. PMID- 8004517 TI - Changes in utilization of dental services of Alberta's universal dental plan for the elderly. AB - Since 1973, Alberta's dental plan for the elderly has made government-sponsored, premium-free comprehensive care by dentists and denturists available to all residents of the province over age 64. Details on the numbers and types of different services provided were previously unavailable from the annual reports. However, an examination of the plan's six-million records, covering nearly 260,000 different patients from 1978 to 1992, has now made it possible, for the first time, to conduct a detailed analysis of these dental services. Many time related changes have occurred in the types of services provided. The number of removable prosthodontic services declined from 14 per cent of all services offered by dentists in 1978-79 to five per cent of these services in 1991-1992, but the services provided by denturists increased by a factor of four. The relative number of surgical and restorative dentistry services offered by dentists also declined. Preventive services grew modestly, but periodontal services grew dramatically from three per cent of all services provided by dentists to 22 per cent. These shifts in services from prosthodontics, restorative dentistry and oral surgery to preventive and periodontic services have important implications for the planning and administration of dental plans for the elderly. PMID- 8004518 TI - Continuity of dental treatment by users of Alberta's universal dental plan for the elderly. AB - To evaluate the longitudinal utilization of Alberta's Extended Health Benefits dental plan for the elderly, its use over the preceding 13 years by patients over age 64, who had used the plan in 1991-92, was examined. Of these 96,596 patients, over half (56 per cent) were female and about two-thirds (68 per cent) received their dental care from a dentist only. However, for the older elderly and for those living outside Calgary and Edmonton, the percentage attending a denturist only or both a denturist and a dentist was greater. Only individuals over age 77, or about 20 per cent of plan participants in 1991-92, were eligible to use the plan over the entire 14-year period examined in this study. However, the regularity of previous annual utilization of the plan was high. About 60 per cent of 70-74 year olds had used the plan for five or more years, while close to 50 per cent of the 80-84 year olds--who were eligible to use the plan for the entire period of the study--had done so in eight or more of the previous 14 years. Despite varying plan eligibility according to patient age, the 96,596 patients who used the plan over the 14-year period made nearly 1.2-million patient visits, at which they received about 3.1-million dental services. The high continuity of annual usage demonstrates that this group is not under-utilizing dental services. PMID- 8004519 TI - Prevention of root caries in older adults. PMID- 8004520 TI - The use of partial dentures incorporating onlays in the treatment of the worn dentition. PMID- 8004521 TI - Dr. Helene Shingles: a life dedicated to geriatric dentistry. PMID- 8004523 TI - Herpes zoster of the trigeminal nerve: the dentist's role in diagnosis and management. AB - Herpes zoster is caused when the varicella/zoster virus that has remained latent since an earlier varicella infection is reactivated. During the prodromal stage, the only presenting symptom may be odontalgia, which may prove to be a diagnostic challenge for the dentist. He or she may carry out emergency treatment that might be irreversible or inappropriate, as well as delay appropriate treatment. With an ever-increasing number of elderly and immunocompromised patients attending the dentist, the dental profession can expect to encounter an increased number of herpes zoster patients. The practising dentist must be familiar with the presenting signs and symptoms of patients experiencing the prodromal manifestations of herpes zoster of the trigeminal nerve. PMID- 8004522 TI - Fibre intake in elderly individuals with poor masticatory performance. AB - The effects of masticatory performance on food selection and nutrient intake in non-institutionalized elderly subjects wearing dental prostheses were investigated. A poor masticatory performance was associated with significantly lower intakes of insoluble and dietary fibre for both sexes (as compared to subjects with a good masticatory performance) and with lower intakes of vitamin A in women only. Further, 37 per cent of subjects with low masticatory performance were taking gastrointestinal drugs, as compared to 20 per cent of subjects with good performance. A reduced consumption of hard-textured fibrous foods due to the deficient masticatory performance of elderly people wearing prostheses may promote the development of gastrointestinal disorders in susceptible individuals. PMID- 8004524 TI - The acidity (pH) and buffering capacity of Canadian fruit juice and dental implications. AB - Excessive consumption of acidic fruit juices is associated with dental morbidity. The pH and buffering capacities of fruit juices packaged and consumed in Canada were measured, and the implications on dental pathology of consuming juices of these qualities are discussed. Canadian fruit juices have a pH below the critical dissolving pH of enamel, and have buffering capacities similar to juices produced and consumed elsewhere in the world. Citrus, apple, and grape juice, or blends of these juices, are all potentially hazardous to teeth. Erosion, attrition, decay and dentinal hypersensitivity may all result from abusive juice drinking. PMID- 8004525 TI - Detection of specific antibody to mycobacterial antigen 60 in tuberculous pleural effusion. AB - BACKGROUND: With the development of the enzyme-linked immunosorbent assay (ELISA) method, serodiagnosis of tuberculosis has been studied by many investigators. Only a few studies have been performed in pleural fluid. This study was designed to evaluate the IgG antibody levels to mycobacterial antigen 60 (Ag60) in pleural fluid, and evaluate its role in the diagnosis of tuberculous pleurisy. METHODS: Eighteen patients with tuberculous pleural effusions and 18 patients with malignant pleural effusions were studied. The levels of IgG antibodies to Ag60 in pleural fluids were measured by ELISA method. RESULTS: The mean titers of IgG against Ag60 in pleural fluids of tuberculous patients (508.3 +/- 382.7 EU) were significantly higher than those of the mean value of the malignant group (131.2 +/- 83.2 EU). In the TB pleurisy group, patients with positive M. tuberculosis cultures from pleural fluids had significantly higher titers than those with negative cultures (796.5 +/- 394.7 vs 277.8 +/- 150.2 EU); patients with impaired immune function had significantly lower titers than those without (138.4 +/- 28.9 vs 650.6 +/- 358.1 EU). Using 250 EU as a cutoff value for a positive test, the sensitivity was 72.2% and the specificity, 94.4%. CONCLUSIONS: ELISA method using Ag60 is a rapid test with an acceptable sensitivity and excellent specificity for differentiation between tuberculous and malignant pleural effusion. PMID- 8004526 TI - MR imaging evaluation of bone marrow signal change in post-irradiation patients with nasopharyngeal carcinoma. AB - BACKGROUND: The normal distribution of red and yellow marrow can be altered by therapeutic irradiation, which causes a well-documented sequence of bone marrow changes. This study measured the T1 signal intensity of the clivus and cervical vertebral bodies of NPC patients who had received a complete course of radiation therapy. METHODS: There were 3 categories of patients: Group I: NPC patients who had radiation myelitis; 14 persons which a total 20 times of MRI. Group II: NPC patients, without radiation myelitis; 6 patients, which a total 6 times of MRI. Group III (control group): patients who received MRI of the cervical spine because of cervical spondylosis or HIVD, were total of 45 patients. In the sagittal section of T1WI, the signal intensity of the bone marrow of clivus and C2 to T1 vertebral bodies was measured. RESULTS: 1). There were homogeneous increases of signal intensity of the bone marrow of clivus and C2 to T1 in Groups I and II. 2). There was no statistical difference between Groups I and II. 3). The increased signal intensity of bone marrow after radiation showed no difference in short and long duration between radiation therapy and MR examinations, indicating that bone marrow signal intensities were increased in NPC patients whether or not they had radiation myelitis. CONCLUSIONS: Signal change in bone marrow may have occurred soon after radiation therapy, and may have persisted for several years. The radiation myelitis always involved the low medulla oblongata to C5 level; however, the bone marrow signal change always extended downward to the T1 level, so bone marrow is more sensitive than the spinal cord and is prone to be affected by irradiation. PMID- 8004527 TI - Clinical observation of neonatal gastrointestinal perforation. AB - BACKGROUND: Gastrointestinal perforation is an infrequent occurrence in neonates. Experience in its management is presented, while also attempting to analyze the factors affecting outcome. METHODS: From 1983 to 1992, 31 neonates with gastrointestinal perforation were treated at Taichung Veterans General Hospital. The medical records of these patients were reviewed thoroughly. In the meantime, Mann-Whitney U and Yates' correction chi square tests were used to analyze the factors predicting the outcomes. RESULTS: There were 21 males and 10 females, among whom 16 were premature births. The median age at diagnosis was 5 day; half (16/31) had occurred during the first 5 days of life. Abdominal distension was the most common manifestation (87%). Hemograms at admission showed leukopenia in 32% (10/31) and thrombocytopenia in 40% (8/20) of the patients. Metabolic acidosis was present in 46% (13/28) of the patients. Peritoneal fluid and preoperative blood cultures were positive in 71% (17/24) and 50% (13/26) of the patients, and both of them had Gram-negative enterobacteriacea as the most common pathogen. The overall mortality rate was 58%. The highest mortality rate was associated with gastric perforation (100%), followed by small bowel (50%) and colon (50%) perforations. The predominant cause of perforation was necrotizing enterocolitis (14/31), with the most common site the terminal ileum (16/29). Four patients with necrotizing enterocolitis had multiple perforations. Others who underwent surgery showed single perforation. The major cause of death in those patients who received operation was sepsis (8/13). An initial arterial pH value higher than 7.25, and surgical procedure performed within two days after disease onset may predict a favorable outcome (p < 0.01). CONCLUSIONS: Gastrointestinal perforation is a life-threatening complication in neonates. A better survival rate can be obtained by cooperation among neonatologists, pediatric surgeons and the nursing staff taking care of these high risk babies. PMID- 8004528 TI - Computed tomography evaluation of chronic paranasal sinusitis. AB - BACKGROUND: Although chronic paranasal sinusitis has been recognized and diagnosed more frequently in recent years, it is still one of the most frequently overlooked disease and a significant source of morbidity and economic loss. Therefore, a further detailed analysis of its clinical pictures and computed tomographic (CT) presentations is necessary for better understanding. METHODS: We collected 230 cases in recent two years and studied their CT manifestations. RESULTS: The pathological changes of sinusitis on CT were classified into four groups: mucosal thickening, mucosal thickening combined with fluid level, fluid level only, and total sinus opacification, in increasing frequency. Maxillary sinus was the most commonly involved sinus. Focal high density areas were noted in 17 sinuses. Ten of them were operated and revealed only thick mucous without evidence of calcification or fungal infection. There was no correlation between the disease duration and the number of sinuses involved. CONCLUSIONS: CT is the image modality of choice in evaluating patients with chronic paranasal sinusitis. PMID- 8004529 TI - Percutaneous balloon valvuloplasty for congenital critical pulmonary stenosis in neonates. AB - BACKGROUND: Percutaneous balloon valvuloplasty (PBVP) was performed on 6 neonates with severe pulmonary stenosis to evaluate its efficacy. METHODS: The 6 studied neonates were aged from 1 to 30 days and weighed 2.5 to 3.3 kg. Follow-up period ranged 6-21 months with a mean of 11.5 +/- 6.3 months. RESULTS: Dramatic improvement after PBVP was obtained not only on the clinical manifestations but also on the hemodynamic data. After percutaneous balloon valvuloplasty, the aortic O2 saturation increased significantly from 71.3 +/- 14.8% to 83.2 +/- 9.3% (p = 0.001) in 5 neonates who had cyanosis before PBVP. The right to left ventricular peak systolic pressure ratio decreased significantly from 1.65 +/- 0.41 to 0.77 +/- 0.27 (p < 0.001). The peak systolic right ventricular pressure dropped significantly from 104.0 +/- 18.8 to 48.8 +/- 13.6 mmHg (p < 0.001). The peak systolic gradient between right ventricle and main pulmonary artery dropped significantly from 83.2 +/- 16.2 to 24.3 +/- 16.3 mmHg (p < 0.05). CONCLUSIONS: The percutaneous balloon valvuloplasty is safe and effective in treating the neonates with congenital critical pulmonary stenosis. PMID- 8004530 TI - Delayed treatment of ankle fracture. AB - BACKGROUND: Cases of old ankle fractures with different delayed treatments in different conditions were collected and evaluated to determine which treatments were optimal for individual type of fractures. METHODS: Sixteen cases of old ankle fractures were managed by open reduction and internal fixation, osteotomy, or removal of loose fragment according to the condition of the fractures between 1977 and 1987. The follow-up period was from 5 to 15 years with mean 7.9 years. The final result was evaluated by a modified performance index. RESULTS: All the 12 patients treated with open reduction and internal fixation for malposition got improved with the mean performance score rising from 37 before operation to 76 after operation. Improvement was also noted in all the 3 patients treated with osteotomy for malunion without significant arthritis, rising from 44 to 88. One patient had painful non-united fragment of medial malleolus, and removal of the loose fragment was done to improve the score from 58 to 96. CONCLUSIONS: Management of old ankle fractures can be effective and beneficial when appropriate treatments are given according to the different conditions of the fracture and joint. PMID- 8004531 TI - Endogenous Candida endophthalmitis: a case report. AB - We experienced a 63-year-old male with a typical finding of endogenous Candida endophthalmitis. Candida albicans was cultured from the vitreous tapping. The patient received oral fluconazole treatment and the symptom improved. In this report, the clinical manifestations of endogenous Candida endophthalmitis and the experience of fluconazole treatment were reported. PMID- 8004532 TI - Anomalous systemic arterial supply to normal basilar segments of the left lower lobe of the lung: a case report. AB - We present a patient who had suffered from mild hemoptysis for six years. Abnormal bronchovesicular breath sounds over the left lower lung filed were noted. The chest film also revealed infiltration over the left lower lung field. High-resolution computed tomography (HRCT), aortogram and pulmonary angiography demonstrated anomalous arterial supply to the basilar segments of the left lower lung without coexistence of pulmonary sequestration. Only total nine cases have been reported in English or Chinese literature. The improvement of diagnostic method has enabled an accurate diagnosis before operation with non-invasive examination. Also, this congenital abnormality may not be so rare if meticulously surveyed. PMID- 8004533 TI - Neurological complications of varicella: a report of two cases. AB - Varicella (chickenpox) is the primary infection of Varicella-Zoster virus, characterized by generalized vesicular eruption, fever and mild constitutional symptoms. Chiefly infecting children of 1 to 14 years of age, the disease has been almost neglected because of its inevitable and benign outcome. Adults are rarely infected with an incidence of less than 20%. These two cases are presented of normal adults with marked neurological complications 10 and 14 days, respectively, following typical skin eruption of varicella. The first case developed transverse myelitis and the second, an encephalomyelitis. Neurological complications are very rare post-varicella infection. Although prognosis is good and complete recovery is the rule, still some morbidity with neurological sequelae and mortality have been reported. The present cases had extensive neurological deficit, despite aggressive treatment, making a high index of suspicion for differential diagnosis in patients who present with encephalitis. Especially following the typical exanthema of varicella, this possibility is emphasized and the literature is reviewed. PMID- 8004534 TI - Humoral and secretory antibodies to Ureaplasma diversum in heifers following subcutaneous vaccination and vaginal infection. AB - We measured antibody levels in serum and cervicovaginal mucus (CVM) of four heifers vaccinated with two inoculations of killed Ureaplasma diversum strain 2312 in incomplete Freund's adjuvant (IFA) two weeks apart, and six heifers given a placebo. Two weeks later, the vaccinates and four placebo heifers, were challenged by intravaginal inoculation with 6.4 x 10(8) colony-forming units of the homologous U. diversum strain. The remaining two placebo heifers served as unvaccinated, unchallenged controls. Antibody levels in serum and CVM of all heifers were determined by an enzyme-linked immunosorbent assay (ELISA). Vaccination stimulated specific IgG1 and IgG2 responses in serum and CVM but only a slight IgM and no IgA response. In both vaccinate and placebo heifers, subsequent intravaginal challenge resulted in a granular vulvitis (GV) with a predominant IgA response in the CVM. The GV gradually subsided during the 35 day observation period but ureaplasmas were consistently demonstrated by culture. We concluded that subcutaneous vaccination stimulated a specific, albeit nonprotective, IgG response in serum and CVM. In contrast, vaginal infection primarily induced a mucosal IgA response. PMID- 8004535 TI - Immune response of heifers to vaginal submucosal or subcutaneous vaccination and intravaginal challenge with Ureaplasma diversum. AB - Twenty beef heifers were randomly assigned to five equal groups and vaccinated: Group 1--in vaginal submucosa (VM) with Ureaplasma diversum ultrasonicated whole cells (WC) in complete Freund's adjuvant (CFA); Group 2--in VM with U. diversum cell membranes (CM) in CFA; Group 3--subcutaneously (SC) with CM in CFA; Group 4- in VM with CM alone; and Group 5--in VM with phosphate buffered saline (PBS) in CFA. A second vaccination with the same antigens in incomplete Freund's adjuvant was given after four weeks, and three weeks later, all heifers were challenged intravaginally with 3.6 x 10(7) colony-forming units (CFU) of U. diversum strain 2312. Immunoglobulins that reacted with U. diversum were measured in serum and cervicovaginal mucus (CVM) by an enzyme-linked-immunosorbent assay. In groups 1 and 2, vaccination by the VM route with WC or CM antigens, stimulated high levels of U. diversum-reactive IgG1 and IgG2 antibodies in serum as well as CVM, but a low IgA response only in CVM. In group 4, VM vaccination with CM (no adjuvant) elicited a minimal IgG1 and IgG2 response in serum and CVM. In group 3, SC vaccination with CM antigen stimulated high IgG1 and IgG2 reactivity in both serum and CVM, but no IgA reactivity. Very little IgM reactivity was detected in the four vaccinated groups. Intravaginal challenge resulted in characteristic granular vulvitis in all vaccinated and control heifers, with all animals remaining culture-positive for the 35 day observation period. The infection stimulated a marked increase in the specific IgA response in CVM of the three groups vaccinated with either, adjuvanted antigen.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8004536 TI - Effects of Ureaplasma diversum on bovine oviductal explants: quantitative measurement using a calmodulin assay. AB - Calmodulin (CAM) acts as an intracellular regulator of calcium, an important mediator of many cell processes. We used the CAM assay and electron microscopy to investigate the effects of Ureaplasma diversum on bovine oviductal explants obtained aseptically from slaughtered cows. A stock suspension of U. diversum (treated specimens) and sterile broth (controls) was added to replicates of cultured explants and incubated at 38 degrees C in an atmosphere of 5.5% CO2 for 48 hours. Explants were examined for ciliary activity, extracellular CAM loss, and for histological and ultrastructural changes. Explants and their culture media were examined for changes in CAM concentration. All experiments were replicated three times. In addition, U. diversum, medium and broth were assayed for CAM content. The concentrations of CAM in explants and media changed significantly (p < 0.05) in samples which were inoculated with U. diversum when compared to controls. The controls and infected specimens did not differ histologically or ultrastructurally, but U. diversum was seen to be closely associated with infected explant tissue. In view of this close affinity it is assumed the loss of CAM from the oviductal cells was causally related, but this was not proven. The failure to show cell membrane injury on light and electron microscopic examination was probably related to the short duration of the experiment and may only point out the sensitivity of the CAM assay in detecting early cell membrane injury. Compromise in characteristics of the medium to support both, the viability of oviductal cells and U. diversum limited the experimental time to 48 hours.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8004538 TI - Effects of diet on fecal occult blood testing in healthy dogs. AB - Six dogs were fed each of nine diets to evaluate the effects of diet on fecal occult blood test results. The diets represented a range of different type (i.e. canned, dry or semi-moist), protein and vegetable constituents, and fiber contents. Each diet was fed twice daily for five consecutive days; fecal samples were collected twice daily on days 4 and 5. An o-tolidine test kit and a guaiac paper test kit for fecal occult blood were used. Two hundred and sixteen fecal samples were analyzed (24 samples/diet). When using the guaiac test the following positive results were obtained from fecal samples from dogs consuming a canned meat- and vegetable-based diet (24/24 samples); a canned meat-based diet (24/24 samples); a dry corn and poultry-based diet (9/24 samples); a dry corn, wheat, and meat meal diet (4/24 samples), a canned poultry-based diet (1/24 sample) and a semi-moist soybean meal-based diet (2/24 samples). A total of 64 samples were positive using the guaiac test. Using the o-tolidine test, no samples were positive. The difference between the number of positive results with each test kit was highly significant (p < 0.001). Results indicate that 1) diet affects the specificity of guaiac test fecal occult blood results in the dog and 2) positive o-tolidine test results were not caused by diets fed in the study. PMID- 8004537 TI - Experimental evaluation of a commercial footrot vaccine against native Canadian strains of Dichelobacter nodosus. AB - Two serotypes of the anaerobic bacterium Dichelobacter nodosus were used to experimentally infect young sheep resulting in infectious pododermatitis or footrot characteristic of the natural disease in sheep. The specific serotypes of D. nodosus were reisolated from the feet and identified using immunofluorescent microscopy of hoof scrapings. Prior immunization of sheep with a commercially available bacterin containing whole cell preparations of ten strains of D. nodosus resulted in serum IgG reactive to a serotype of D. nodosus common to the vaccine. Immunization also produced serum IgG reactive to a serotype of D. nodosus not incorporated in the vaccine. A less severe infection occurred in the immunized sheep than in the controls regardless of the serotype of bacteria used to infect them. Clinical lameness and lesion severity were milder in sheep infected with the serotype of D. nodosus common to the vaccine. Western blot analysis of sera from convalescent sheep showed cross-reactive antibodies to nonfimbrial cell surface proteins, as well as bacterial lipopolysaccharide. Such cross-reactivity may explain the partial protection seen in animals infected with a serotype distinctive from the ones in the vaccine. Despite the historical emphasis of fimbrial immunogens in ovine footrot this study using a new model of experimental ovine footrot suggests other surface antigens may also be important in protective immunity. PMID- 8004539 TI - Comparison of the effects of ketoprofen and flunixin meglumine on the in vitro response of equine peripheral blood monocytes to bacterial endotoxin. AB - The purpose of this study was to investigate the in vitro effects of flunixin meglumine, a cyclo-oxygenase inhibitor, and ketoprofen, a reported cyclo oxygenase and lipoxygenase inhibitor, on the synthesis of cyclo-oxygenase end products thromboxane B2 and prostaglandin E2, lipoxygenase derived 12 hydroxyeicosatetraenoic acid, tumor necrosis factor and tissue factor. Six adult horses were each randomly administered flunixin meglumine (1.1 mg/kg) or ketoprofen (2.2 mg/kg) intravenously every 12 hours with the drug treatments separated by two weeks. Blood samples were obtained prior to initiating treatment, the last day of treatment and for two consecutive days after the termination of treatment for measurement of serum concentrations of thromboxane B2 as well as isolation of peripheral blood monocytes. Quantitation of unstimulated, endotoxin- and calcium ionophore-induced synthesis of thromboxane B2, prostaglandin E2, 12-hydroxyeicosatetraenoic acid, tumor necrosis factor and tissue factor by peripheral blood monocytes was performed in vitro. Both flunixin meglumine and ketoprofen significantly decreased serum concentrations of thromboxane B2 demonstrating in vivo cyclo-oxygenase inhibition. There were no significant differences between drug treatment groups in the in vitro production of thromboxane B2, prostaglandin E2, 12-hydroxy-eicosatetraenoic acid, tumor necrosis factor or tissue factor. This study does not identify significant differences between the effects of flunixin meglumine and ketoprofen. PMID- 8004540 TI - A comparison of systolic blood pressure measurement obtained using a pulse oximeter, and direct systolic pressure measurement in anesthetized sows. AB - Systolic blood pressure measurement obtained with a pulse oximeter has been compared to values obtained by other indirect methods in man. Direct pressure measurement is subject to less error than indirect techniques. This study was designed to compare systolic pressure values obtained using a pulse oximeter, with values obtained by direct arterial pressure measurement. The pulse oximeter waveform was used as an indication of perfusion. A blood pressure cuff was applied proximal to the pulse oximeter probe. The cuff was inflated until the oximeter waveform disappeared, this value was recorded as the systolic pressure at the disappearance of the waveform (SPD). The cuff was inflated to a pressure > 200 mmHg, then gradually deflated until the waveform reappeared, this value was recorded as the systolic pressure at reappearance of the waveform (SPR). The average of the two values, SPD and SPR, was calculated and recorded as SPA. The study was performed in sows (n = 21) undergoing cesarean section under epidural anesthesia and IV sedation. A total of 280 measurements were made of SPD, SPR and SPA. Regression analysis of SPA and direct measurement revealed a correlation coefficient (r) of 0.81. Calculation of mean difference (bias) and standard deviation of the bias (precision) for direct pressure--SPA revealed a value of 1.3 +/- 12.1. When compared with direct measurement, the correlation of this technique was similar to that recorded for other indirect techniques used in small animals. This indicates that this technique would be useful for following systolic pressure trends.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8004541 TI - Effects of supplemental chromium on antibody responses of newly weaned feedlot calves to immunization with infectious bovine rhinotracheitis and parainfluenza 3 virus. AB - The objective of this study was to determine the effect of supplemental dietary chromium (Cr) on antibody responses of feedlot calves. Fifty-five newly weaned calves were divided into two groups, 28 that received supplemental Cr and 27 that did not, and were immunized with a commercial vaccine against bovine infectious rhinotracheitis virus (IBR) and bovine parainfluenza virus type 3(PI-3). Sera harvested from blood sampled preimmunization, and at days 14 and 28 postimmunization (PI), were assayed for anti-IBR and anti-PI-3 antibody titers. Individual calves were also scored as seroconverters if day 14 or 28 PI titers were > or = 3 times the value of the preimmunization titer. Thirty-five calves did not seroconvert to either antigen. Of 20 IBR seroconverters, 15 calves were from the Cr-supplemented group while only five calves were controls (p = 0.007). There was no treatment difference in the number of PI-3 seroconverters. Least squares analysis of actual antibody titers revealed that Cr supplementation increased the magnitude of the peak antibody response to the IBR (p = 0.003), but had no effect on anti-PI-3 antibody titers. These data confirmed and extended our previous observations that supplemental Cr can be immunomodulatory in cattle. PMID- 8004542 TI - Flow cytometric analysis of ovine peripheral blood lymphocytes. AB - Leukocyte suspensions were prepared from the peripheral blood of 12 sheep three times at two month intervals beginning at 12 months of age. Monoclonal antibodies and flow cytometric analysis were used to characterize the cells. There were no significant differences over time therefore the data from the three time intervals were pooled. The mean percentages and ranges (minimum to maximum) of the major lymphocyte subtypes were: B-cells (29.6%, 11-50), gamma delta T-cells (36.6%, 22-68), CD4+ T-cells (14.1%, 8-22) and CD8+ T-cells (12.0%, 4-22). Lymphocyte subtype percentages appeared less variable within than between individuals. Two populations of B-cells were noted; one population had more cytoplasm and light scatter characteristics similar to monocytes while a second population of B-cells was more typical of small lymphocytes. The nature of the large B-cells requires further study. PMID- 8004543 TI - The anatomy of the vertebral column of the Nubian goat: a peculiarity of the arcus vertebrae C5, C6 and C7 forming large spatia interarcualia. PMID- 8004544 TI - Induction of acute bronchopneumonia in mice by intrabronchial inoculation of Pasteurella haemolytica serotype 1. AB - Dose dependent pulmonary lesions of acute bronchopneumonia were induced in male, outbred Swiss Webster mice by intrabronchial inoculation of Pasteurella haemolytica. Five exponential dilutions ranging from 5 x 10(4) to 5 x 10(8) colony forming units per mL (CFU/mL) of Pasteurella haemolytica serotype 1 were inoculated into five groups of mice. Mice were killed by cervical dislocation 24 hours postinoculation. Pulmonary lesions occurred in mice of all five groups, however, 5 x 10(7) CFU/mL was the minimal dose which consistently produced lesions. Focal parenchymal necrosis, suppurative bronchiolitis, and flooding of interalveolar septa and alveoli by edema fluid, fibrin, neutrophils and macrophages, were observed microscopically. We conclude that outbred Swiss Webster mice can be used as a model for the study of selected disease mechanisms of acute lung inflammation and that this model may be used to determine some of the pathogenic mechanisms involved in the development of pulmonary lesions in bovine pneumonic pasteurellosis. PMID- 8004545 TI - Secreted proteases from Actinobacillus pleuropneumoniae serotype 1 degrade porcine gelatin, hemoglobin and immunoglobulin A. AB - It was found that 48 hour cultures of Actinobacillus pleuropneumoniae secreted proteases into the medium. Electrophoresis in polyacrylamide gels (10%) copolymerized with porcine gelatin (0.1%), of the 70% (NH4)2SO4 precipitate from the culture supernatants, displayed protease activities of different molecular weights: > 200, 200, 90, 80, 70 and 50 kDa. They had activity over a broad range of pHs (4-8), with an optimal pH of 6-7. All were inhibited by 10 mM EDTA, and reactivated by 10 mM calcium. They were stable at -20 degrees C for more than a month. The proteases also degraded porcine IgA and porcine, human, and bovine hemoglobin, although they appeared to be less active against the hemoglobins. The IgA was totally cleaved in 48 h, using supernatants concentrated with polyvinyl pyrrolidone or the 70% (NH4)2SO4. Extracellular proteases could play a role in virulence. PMID- 8004546 TI - Attaching and effacing and enterotoxigenic Escherichia coli associated with enteric colibacillosis in the dog. AB - The objective of this study was to describe observations from cases of enteric colibacillosis in the dog. Thirteen cases of canine enteric colibacillosis were diagnosed from routine necropsy submissions to our diagnostic laboratory from 1980 to 1992. In all cases there was a clinical history of gastrointestinal disease associated with histological and bacteriological evidence of either attaching and effacing Escherichia coli (AEEC) or enterotoxigenic Escherichia coli (ETEC) infection. Of these 13 cases of enteric colibacillosis, 12 were associated with AEEC and one with ETEC. Eight of the 12 AEEC isolates were available for study. They were of various serogroups, non-hemolytic, and negative for the genes coding for fimbrial antigens F4, F5, F6, F41 and F165; enterotoxins STap, STb and LT; and verotoxins VT1 and VT2. These eight isolates were EAE positive (E. coli attaching and effacing) by colony hybridization; six of these were also EAF-positive (EPEC adherence factor), and six were BFP-positive (bundle forming pilus). The ETEC isolate was negative for the EAE, EAF and BFP determinants and for the fimbrial antigens tested but was positive for the STap and STb genes. Most of the dogs affected with enteric colibacillosis originated from kennels and pet shops and were aged between 1.5 and 3 months. Coinfection with other enteric pathogens was identified in eight of these 13 cases. This study showed that Escherichia coli should be considered of causal significance when investigating diarrheal disease in dogs, particularly in puppies. PMID- 8004547 TI - Sialoglycoprotease of Pasteurella haemolytica A1: detection of antisialoglycoprotease antibodies in sera of calves. AB - Log phase culture supernate from Pasteurella haemolytica biotype A, serotype 1 contains a proteolytic enzyme specific for O-sialoglycoproteins. Using two methods, Western immunoblotting and enzyme neutralization assay, it was demonstrated that certain bovine sera from two previous P. haemolytica A1 vaccination and challenge trials contained antibodies (Ab) (isotypes IgG1 and IgG2 on Western immunoblot) to the sialoglycoprotease (Gcp). In these trials, selected calves were vaccinated twice with either the commercial culture supernate vaccine Presponse or given phosphate-buffered saline (PBS). One trial was conducted during spring, P. haem XIX, and the other during the winter, P. haem XXI. Although there was no clear evidence for induction of anti-Gcp in response to vaccination, several calves seroconverted following intrapulmonary challenge with live P. haemolytica A1. This is the first report of anti-Gcp Ab in bovine sera. The results indicated that the Gcp is immunogenic and that the bacterium produces the enzyme in vivo. Further, animals with an anti-Gcp response had less pneumonia at necropsy, suggesting the Gcp may induce protective immunity. PMID- 8004548 TI - Preliminary characterization of the structural proteins of the coronaviruses, sialodacryoadenitis virus and Parker's rat coronavirus. AB - A procedure was developed for the partial purification of the rat coronaviruses, sialodacryoadenitis virus (SDAV) and Parker's rat coronavirus (PRC). The SDAV and PRC were replicated in L-2 cell monolayer cultures, precipitated with ammonium sulphate, and further concentrated using sucrose density gradient centrifugation. The major SDAV and PRC proteins were identified by immunoblotting and compared with those of the JHM strain of mouse hepatitis virus (MHV-JHM). Monoclonal antibodies (MAb) against the M protein of JHM recognized proteins interpreted to be slightly smaller in immunoblots of SDAV and PRC (22.8 vs 23K for JHM). Similarly, a monoclonal antibody against the JHM N protein reacted with proteins of 53K in SDAV and PRC (vs 56 K for JHM). Polyclonal antisera to all three viruses also cross-reacted with the M and N proteins. Some cross-reactivity amongst the S proteins was observed. Based on these data, the structural proteins of the rat coronaviruses, SDAV and PRC are closely related to those of MHV-JHM. PMID- 8004549 TI - Ethics of medicine and science. PMID- 8004550 TI - Unfit drivers. PMID- 8004551 TI - Splitting hairs over euthanasia. PMID- 8004552 TI - Cutting costs by targeting prescribing practices. PMID- 8004553 TI - Cutting costs by targeting prescribing practices. PMID- 8004555 TI - Horse products for tetanus prophylaxis. PMID- 8004554 TI - Folic acid supplementation to prevent neural tube defects. PMID- 8004556 TI - Family physicians and nurse practitioners: guidelines, not battlelines. PMID- 8004558 TI - The family physician-nurse practitioner dyad: indications and guidelines. PMID- 8004557 TI - Screening in the office for elevated cholesterol levels: still a dilemma. PMID- 8004559 TI - System for Health Area Resource Planning (SHARP): an application to Ontario medical school enrollment. PMID- 8004561 TI - Nurse practitioners and physicians: competition or collaboration? PMID- 8004562 TI - Dealing with the unexpected one of challenges facing Canada's military MDs in Bosnia. PMID- 8004560 TI - Methodologic quality and relevance of references in pharmaceutical advertisements in a Canadian medical journal. AB - OBJECTIVE: To evaluate the methodologic quality and relevance of references in pharmaceutical advertisements in the Canadian Medical Association Journal (CMAJ). DESIGN: Analytic study. DATA SOURCE: All 114 references cited in the first 22 distinct pharmaceutical advertisements in volume 146 of CMAJ. MAIN OUTCOME MEASURES: Mean methodologic quality score (modified from the 6-point scale used to assess articles in the American College of Physicians' Journal Club) and mean relevance score (based on a new 5-point scale) for all references in each advertisement. MAIN RESULTS: Twenty of the 22 companies responded, sending 78 (90%) of the 87 references requested. The mean methodologic quality score was 58% (95% confidence limits [CL] 51% and 65%) and the mean relevance score 76% (95% CL 72% and 80%). The two mean scores were statistically lower than the acceptable score of 80% (p < 0.05), and the methodologic quality score was outside the preset clinically significant difference of 15%. The poor rating for methodologic quality was primarily because of the citation of references to low-quality review articles and "other" sources (i.e., other than reports of clinical trials). Half of the advertisements had a methodologic quality score of less than 65%, but only five had a relevance score of less than 65%. CONCLUSIONS: Although the relevance of most of the references was within minimal acceptable limits, the methodologic quality was often unacceptable. Because advertisements are an important part of pharmaceutical marketing and education, we suggest that companies develop written standards for their advertisements and monitor their advertisements for adherence to these standards. We also suggest that the Pharmaceutical Advertising Advisory Board develop more stringent guidelines for advertising and that it enforce these guidelines in a consistent, rigorous fashion. PMID- 8004563 TI - Physicians cannot be educated in isolation from public concerns, ACMC conference told. PMID- 8004564 TI - Canada's obstetricians and gynecologists set sights on new role in women's health. PMID- 8004565 TI - Staging of prostate cancer. PMID- 8004566 TI - Oral etoposide in the treatment of hormone-refractory prostate cancer. AB - BACKGROUND: Hormone-refractory prostate cancer generally remains a chemotherapy resistant tumor and therefore warrants the continued evaluation of promising agents. METHODS: Twenty-two eligible patients with hormone-refractory prostate cancer were treated with oral etoposide at a dosage of 50 mg/m2/day for 21 days in a 28-day cycle. Response was evaluated using standard solid tumor response criteria. RESULTS: There were two partial responses of 6 and 14 months' duration, respectively. Two patients had disease stabilization, one for 6 months and one for 12 months. Median survival was 31 weeks, with an overall 1-year survival of 30%. Reversible alopecia and myelosuppression were the primary toxicities noted. CONCLUSIONS: Single-agent oral etoposide has minimal activity in patients with hormone-refractory prostate cancer. PMID- 8004567 TI - Carcinoma in situ of the urinary bladder. Clues to host involvement in human carcinogenesis. AB - BACKGROUND: Carcinoma in situ (CIS) of the urinary bladder is a neoplasm of uncertain biologic behavior. It rarely occurs as the primary disease and exists most often in association with high grade, invasive tumors. The unfavorable prognosis ascribed to CIS may not be due to tumor-related factors but to low host resistance or to host-tumor relationships established for previous or co-incident invasive cancers. The scant available evidence indicates that a large proportion of patients with primary CIS have a low frequency of muscle invasion and death from disease. METHODS: Of 2000 patients with bladder neoplasms in our pathology files and tumor registry, 102 had CIS confirmed on histologic review. There were 29 cases of primary CIS and 73 cases of secondary CIS. These cases were compared, with an emphasis on patient outcome. RESULTS: The data indicate that primary and secondary CIS are histologically identical lesions whose effect on patients is related mainly to the presence of multifocal disease, often associated with previous or coincident invasive cancers. Progression or death from disease is unusual among patients presenting with primary CIS but common among individuals with CIS associated with other bladder cancers. CONCLUSION: The authors suggest that the appearance of urothelial CIS identifies patients with at least localized resistance to the development of invasive bladder cancer. The degree of patient resistance to carcinogenic events leading to bladder carcinoma is manifested by the type, grade, and stage of their initial neoplasms. PMID- 8004568 TI - Early detection of nonpolypoid cancers in the rectal remnant in patients with familial adenomatous polyposis/Gardner's syndrome. AB - BACKGROUND: Invasive cancer occurs in the rectal remnant of patients with familial adenomatous polyposis (FAP). METHODS: A long term surveillance proctoscopy program was performed on 25 patients with an established diagnosis of FAP or Gardner's syndrome. RESULTS: The surveillance revealed small nonpolypoid cancer of the rectal remnant in two patients. One cancer, which measured 5 mm, was restricted to the mucosa, whereas the other, measuring 10 mm at its greatest dimension had invaded the submucosa. On proctoscopy, both the lesions were characterized by a reddish depression, surrounded by marginal elevations. Both of these cancers were composed of well differentiated adenocarcinoma without any adenomatous component. CONCLUSIONS: The authors' experience suggests that nonpolypoid cancers do exist in FAP/Gardner's syndrome and that careful follow-up seems necessary in patients with a diagnosis, especially in consideration of the possible development of nonpolypoid lesions. PMID- 8004569 TI - Prognostic factors and significance of chemotherapy in patients with recurrent or metastatic transitional cell cancer of the urinary tract. AB - BACKGROUND: Prognostic factors for patients with disseminated transitional cell carcinoma of the urothelium (TCC) has been examined only in patients selected for studies with chemotherapy. This study was performed to determine important prognostic factors in patients with disseminated TCC and evaluate the impact of chemotherapy. METHODS: The prognostic factors for survival were analyzed in 240 patients with disseminated TCC admitted from 1976 to 1992. Information on prior medical history, baseline variables, and treatment were related to survival after dissemination. Both univariate and multivariate analyses were performed to identify factors of independent importance. RESULTS: Univariate analyses indicated that performance status; hemoglobin; leukocyte count; platelet count; concentrations of serum creatinine, aspartate aminotransferase, lactate dehydrogenase, and alkaline phosphatase; hydronephrosis; bone metastases; disease extension; and chemotherapy were related significantly to survival. Multivariate analysis demonstrated that a good performance status, a normal alkaline phosphatase concentration, and a normal serum creatinine concentration were independent prognosticators for long survival. When chemotherapy was included in the analysis, it was found to be the most important independent prognostic factor in conjunction with alkaline phosphatase and performance status. CONCLUSION: This study has established the importance of performance status and alkaline phosphatase as the most important prognostic factors of survival in patients with disseminated TCC regardless of treatment. Chemotherapy was found to be an independent prognostic variable that indicates a possible prolongation of survival in patients receiving chemotherapy. PMID- 8004571 TI - A pilot study of etoposide, vinblastine, and doxorubicin plus involved field irradiation in advanced, previously untreated Hodgkin's disease. AB - BACKGROUND: Advanced stage Hodgkin's disease (HD) usually is treated with combination chemotherapy with or without supplemental irradiation. The risk of significant acute and long term toxicity when the chemotherapy regimen contains alkylating agents has provided the impetus for the development of systemic combinations that do not include alkylating agents. This trial was designed to assess the toxicity and efficacy of a regimen of etoposide, vinblastine, and doxorubicin (EVA) as part of a combined modality approach in patients with moderate to high risk HD. METHODS: This was a prospective pilot study that included 26 previously untreated patients. They received 6 cycles of EVA, and complete responders received low dose (1500-2500 cGy) involved field radiation. RESULTS: Four patients were hospitalized for sepsis during chemotherapy. Complete response was achieved in 54% of patients, and 46% patients experienced induction failures. Two year failure-free survival is 44%, while 2 year overall survival is 86%. Median follow-up is 27 months. CONCLUSIONS: The EVA regimen is no more efficacious than other programs already in use and may be less so. It also is potentially leukemogenic because of the presence of etoposide. New combinations that do not contain etoposide should be explored in therapy programs for advanced HD in the hopes of discovering an efficacious treatment program that has minimal long term side effects. PMID- 8004570 TI - PRAD-1 (CCND1)/cyclin D1 oncogene amplification in primary head and neck squamous cell carcinoma. AB - BACKGROUND: Abnormalities in chromosome 11q13 regions have been frequently found in head and neck squamous carcinoma. Recent studies indicate that the PRAD-1 (also CCND1), which encodes cyclin D1, is a putative oncogene that is an important component of this region. METHODS: DNA was extracted from 32 snap frozen specimens from primary head and neck squamous carcinomas. DNA from peripheral blood lymphocytes, normal mucosa, and salivary gland tissue were used as controls. A genomic DNA probe containing the first exon of PRAD-1 was used for hybridization with specimen DNAs by the Southern technique. A 5.6-kb genomic DNA probe of immunoglobulin heavy chain was used as an internal standard for assessing PRAD-1 amplification. RESULTS: Eleven (34.4%) squamous carcinoma specimens showed PRAD-1 amplification (2- to 10-fold). Although no significant statistical correlation among amplification status, grade stage, and DNA ploidy was observed in this small cohort, amplification was more noted in high grade, high stage, and aneuploid tumors. A highly statistical correlation between PRAD-1 amplification and proliferative activity was noted (P > 0.001). CONCLUSION: The results of this study indicate that PRAD-1 amplification appears to be a late event in the tumorigenesis of head and neck carcinoma and is associated often with a subset of aggressive tumors and high proliferation neoplasms. PMID- 8004572 TI - B-cell malignancy after low grade T-cell lymphoma. AB - BACKGROUND: Low grade, small lymphocytic, non-Hodgkin's lymphoma, was diagnosed in a 38-year-old woman. Thirty months after the initial diagnosis was made, a population of lymphoid cells with pathologic morphology was found in the patient's peripheral blood (PB). Cell phenotyping was performed and monoclonality was analyzed in cells obtained from a removed lymph node (LN) and the PB of the patient. METHODS: The cell phenotype was examined with immunofluorescence techniques using antibodies against SIg and monoclonal antibodies against CD1, CD3, CD4, CD5, CD8, CD19, and the kappa, and lambda light chains. Gene rearrangement analysis for monoclonality determination was performed with restricted DNA (EcoRI, Hin-dIII and BamHI) hybridized with either 32P-labeled T cell receptor DNA probe (TcR-beta) or immunoglobulin-heavy chain probe (JH). RESULTS: With regard to the cell population of the removed LN, cell phenotyping showed the predominance of CD4+ T-cells over a polyclonal B-cell population. Gene rearrangement analysis proved the monoclonal nature of the T-cells and the polyclonal nature of the B-cells. As to the PB, gene rearrangement and cell phenotyping of the lymphocytes showed the predominance of monoclonal kappa type B cells over polyclonal T-cells. CONCLUSIONS: The data obtained suggest two unrelated lymphoproliferative diseases in this patient, expressed as monoclonal T cell population in LN and as monoclonal B-cell population in PB. PMID- 8004573 TI - The spectrum of chronic lymphoproliferative disorders in Chinese people. An analysis of 64 cases. AB - BACKGROUND: Chronic lymphoproliferative disorders are considered rare in Oriental patients and are thought to constitute only 2% of all leukemias in these patients, compared to 20-30% in Western patients. We conducted a retrospective analysis of Chinese patients with chronic lymphoproliferative disorders to define the frequency and spectrum of these disorders. METHODS: A consecutive series of Chinese patients with leukemia and lymphoproliferative disorders seen at two regional hospitals in Hong Kong were analyzed retrospectively. The diagnosis of chronic lymphoproliferative disorders was based on morphologic and immunologic criteria proposed by the French-American-British Cooperative Study Group. RESULTS: Sixty-four Chinese patients with chronic lymphoproliferative disorders were identified, and these patients constituted 19% of a total of 342 cases of leukemia diagnosed in 3 years. Chronic lymphocytic leukemia was the most common form, occurring at a frequency of 12.5% of all leukemias. The clinicopathologic features of these patients were similar to those of Western patients, except that Chinese patients tended to present with more advanced (Rai's Stages III and IV; Binet's Stage C) and bulky (splenomegaly > 9 cm) disease, and expressed lambda light chain about six times more frequently. Other chronic lymphoproliferative disorders identified in this study included prolymphocytic leukemia, mantle zone lymphoma, hairy cell leukemia, splenic lymphoma with villous lymphocytes, large granular lymphocyte leukemia, and Sezary syndrome. The authors did not identify any case of human T-cell lymphotropic virus-I-related lymphoproliferative disorders within the study period. CONCLUSION: In addition to providing the frequencies of various chronic lymphoproliferative disorders in southern Chinese people, this study also showed that these disorders no longer should be considered rare in this population. Inherent biologic differences between lymphoproliferative disorders in Chinese and Western patients also may exist. PMID- 8004574 TI - Late doxorubicin-associated cardiotoxicity in children. The possible role of intercurrent viral infection. AB - BACKGROUND: The most frequently encountered doxorubicin related cardiac toxicity is a dose-related myocardial dysfunction occurring 1-6 months after chemotherapy. Recently, late cardiotoxicity has been the focus of interest. This paper explores the possibility that acute intercurrent viral illness may trigger late cardiotoxicity. METHODS: Thirty selected pediatric patients were followed for changes in their echocardiographically measured fractional shortening (FS) for 2 10 years after completion of their doxorubicin chemotherapy. They were divided according to the dose of doxorubicin they received (< 300 mg/m2 or > or = 300 mg/m2) and to whether the manifestations of an acute intercurrent viral illness during the observation period were documented. Eleven patients experienced such infections. RESULTS: Changes in FS demonstrated two different responses. The usual response to doxorubicin was a gradual, dose-related fall in FS, followed by recovery; while the second response included an unexpected, late, sudden decrease in FS. Four patients in the low dose subgroup experienced an acute intercurrent viral illness, but none of these demonstrated the unexpected decrease. Of the seven patients who acquired such illness in the high dose subgroup, five demonstrated the sudden, late decrease in FS, with two of them developing severe, reversible congestive heart failure. CONCLUSIONS: The most likely explanation for the late, sudden decrease in FS is an additional stress in patients who already have sustained subclinical cardiac damage as a result of their doxorubicin chemotherapy. An acute intercurrent viral illness may have triggered late cardiac dysfunction in some of these patients. PMID- 8004575 TI - Safety and cost effectiveness of early hospital discharge of lower risk children with cancer admitted for fever and neutropenia. AB - BACKGROUND: Standard treatment for fever during periods of chemotherapy-induced neutropenia includes hospitalization and administration of intravenous antibiotics until the patient is afebrile and no longer neutropenic. This study prospectively evaluates the safety and cost-effectiveness of early discharge of selected low risk children before recovery from neutropenia. METHODS: We studied 74 children with cancer during 131 consecutive admissions for fever during a period of neutropenia. All patients initially were hospitalized and received broad-spectrum antibiotics. Intravenous antibiotic therapy was discontinued, and the patients promptly were discharged even if they had an absolute neutrophil count (ANC) of less than 500 cells/mm3 as long as they were afebrile, appeared clinically well, had negative cultures, exhibited control of local infection, and showed hematologic evidence of bone marrow recovery. RESULTS: Intravenous antibiotics were discontinued in 82 cases (63%) before recovery of the ANC to more than 500 cells/mm3, and 78 patients were discharged immediately. None of 70 patients discharged while neutropenic but exhibiting a rising ANC at the time of discharge developed recurrent fever and required readmission. Thirty of these children had an improving localized infection when intravenous antibiotics were discontinued and completed a course of oral antibiotics at home. The estimated mean savings in hospital charges due to early discharge was $5058 per patient. CONCLUSIONS: Low risk children with cancer who are hospitalized and treated for fever and neutropenia but appear clinically well may have intravenous antibiotics discontinued and be discharged safely irrespective of the ANC, as long as their granulocyte count is rising. This approach shortens hospital stays and results in considerable cost savings. PMID- 8004576 TI - Recombinant alpha-2B interferon treatment for childhood T--lymphoblastic disease in relapse. A Pediatric Oncology Group Phase II study. AB - BACKGROUND: Children with chemotherapy refractory T-cell lymphoblastic leukemia/lymphoma were given alpha-interferon (alpha-IFN) to evaluate the efficacy and toxicity of this biologic response modifier. METHODS: Twenty children with T-cell acute lymphoblastic leukemia (T-cell ALL) in marrow relapse and one patient with mediastinal recurrence of T-cell non-Hodgkin's lymphoma (T cell NHL) were enrolled. All patients had failed at least two previous multiagent drug trials. Recombinant alpha-IFN was given at 30 million U/M2/dose intravenously or subcutaneously for 10 doses over 14 days, followed by 3 doses per week until disease progression occurred. RESULTS: One child had a complete response (< 5% blasts) and three patients a partial response (5-25% blasts) in their bone marrow. All patients eventually showed signs of progressive disease. Significant toxicities included cardiac hypofunction in two patients and profound lethargy in two patients. CONCLUSIONS: alpha-IFN is tolerated in children with T cell ALL and T-cell NHL and has activity against chemotherapy resistant disease. PMID- 8004578 TI - Long-term survival associated with metastatic small cell carcinoma of the esophagus treated by chemotherapy, autologous bone marrow transplantation, and adjuvant radiation therapy. PMID- 8004577 TI - Indications for surgical intervention for gastrointestinal emergencies in children receiving chemotherapy. AB - BACKGROUND: Abdominal pain in children receiving chemotherapy for cancer presents the clinician with unique problems due to the altered immunity of these patients or to the oncologic setting. The major clinical decisions regarding these patients are to determine if and when operative intervention is indicated. METHODS: A retrospective study was done to examine the clinical, radiographic, and laboratory findings that indicate the need for surgical intervention. Sixty eight of 1090 children who underwent treatment for cancer from October 1982 to December 1990 developed abdominal complaints requiring them to be hospitalized. Nineteen of these patients underwent exploratory laparotomy (operative), and the other 49 were observed (nonoperative). RESULTS: No significant differences were observed in the phase of chemotherapy, treatment with vincristine or corticosteroids, or the hematologic indices between the operative and nonoperative groups. Eighteen of nineteen patients survived their surgeries. Seventeen (89%) of these laparotomies were positive based on the surgical pathology and the operative report. Peritoneal signs on physical examination (P < 0.001) or pneumatosis intestinalis on abdominal radiographs correlated with positive laparotomies (P = 0.001). CONCLUSIONS: Peritoneal signs on physical examination or pneumatosis intestinalis on abdominal X-rays were associated with and specific for the presence of acute surgical disease of the abdomen in immunocompromised pediatric oncology patients. PMID- 8004579 TI - Overexpression and point mutations of p53 tumor suppressor gene in hepatocellular carcinomas in Hong Kong Chinese people. AB - BACKGROUND: Gene deletion, point mutations, and abnormalities in expression of the tumor suppressor gene p53 in hepatocellular carcinoma have been reported to occur with varying frequency in different geographic regions. METHODS: To assess the expression and point mutation of the p53 gene, 31 patients with hepatocellular carcinomas were examined using Northern blotting, immunohistochemical methods, and DNA sequencing. All patients were Chinese, and 90.3% were positive for hepatitis B surface antigen (HBsAg). RESULTS: p53 transcript or protein was found in 14 (48.4%) of the 31 patients. Detectable p53 mRNA transcripts were found in 10 patients, and p53 protein was detected in 8 patients. In most cases of patients who had detectable p53 mRNA transcripts, the transcripts in the tumors were exhibited at a higher level than they were in the corresponding nontumorous livers. No p53 protein was detected in the nontumorous livers in all 31 patients. Six (23.1%) of the 26 tumors sequenced showed point mutation scattered in exons 5-9. Of these, only two were at codon-249, and the nature of these two mutations was G-to-T transversions. All but one of the six patients with point mutations had overexpression of the gene. CONCLUSIONS: Our results show that scattered point mutations are not uncommon in hepatocellular carcinomas in patients from Hong Kong. The distribution pattern of the mutations seems to have no particular correlation with HBsAg status despite a high prevalence rate of HBsAg positivity in our patients. Consistent with a low aflatoxin exposure, aflatoxin-related specific mutation at codon-249 is much less related to the pathogenesis of hepatocellular carcinoma in Hong Kong Chinese people than in other regions with a high-aflatoxin exposure. PMID- 8004580 TI - Subcutaneous heparin treatment increases survival in small cell lung cancer. "Petites Cellules" Group. AB - BACKGROUND: A positive influence of anticoagulant treatment in small cell lung cancer (SCLC) has been suggested by experimental and clinical data. METHODS: In a multicenter clinical trial, 277 patients with SCLC were randomized either to receive or not to receive subcutaneous heparin injections for 5 weeks at effective doses, which were monitored by blood coagulation tests. All patients received one of the two chemotherapy regimens studied in this trial, for eight courses in the case of patients with complete or partial response, and subsequently were randomized to receive delayed thoracic radiotherapy after these eight courses. RESULTS: In comparison to the 139 patients who did not receive heparin, the 138 patients who received anticoagulant treatment obtained better complete response rates (37% vs. 23%, P = 0.004), better median survival (317 days vs. 261 days, P = 0.01), and better survival rates at 1, 2, and 3 years (40% vs. 30%, 11% vs. 9% and 9% vs. 6%, respectively). At subgroups analysis, the results on survival were obtained for limited forms (P = 0.03) but not for extensive diseases (P = 0.31). No important bleeding or thrombocytopenia was related to heparin treatment. CONCLUSIONS: These results confirm the value of anticoagulant treatment in SCLC, already suspected for warfarin and now proven for heparin, but the modes of administration and the biologic explanations for this activity still warrant further investigation. PMID- 8004581 TI - Patterns of lymphatic spread in thoracic esophageal cancer. AB - BACKGROUND: The cervical nodes have been excluded from the category of regional nodes in cases of thoracic esophageal cancer in the present TNM classifications. METHODS: One hundred and forty-one patients with thoracic esophageal cancer who had undergone extensive radical lymphadenectomy were included in the study. The patterns of early lymph node metastasis from the disease, in terms of lymph node metastases from the intramural tumors or those found in patients with a single metastatic node, were studied. Prognostic significance of the removal of the positive nodes also was examined in relation to the metastatic sites. RESULTS: Of the 47 patients with intramural cancer, only 21% had nodal metastases confined to the mediastinum, 11% had positive cervical nodes, and 23% had jumping metastases to the extramediastinal nodes. Of the 31 patients with a single metastatic node, 61% showed metastasis in a jumping fashion, and 19% had a positive node in the neck. Seventy-four (79.6%) of the 93 patients with vessel invasion also had lymph node metastases, whereas 20 (41.7%) of the 48 patients without vessel invasion had metastases to the lymph nodes (P < 0.001). The 5-year projected survival rate for patients with positive cervical nodes was 27%, with no significant difference in survival rate compared with that for patients with metastatic nodes in the mediastinum or the abdomen. The number of involved nodes was related significantly to outcome: The 5-year survival rates for the 45 patients with negative nodes the 66 patients with one to four positive nodes were 71.8 and 34.2%, respectively (P < 0.01), whereas none of the 27 patients with five or more positive nodes survived more than 3 years after the operation (P < 0.001). CONCLUSIONS: The cervical nodes should be included in the category of regional nodes in cases of thoracic esophageal cancer on the basis of the patterns of early lymph node metastases and the prognostic significance of a lymphadenectomy for metastases to these nodes. PMID- 8004582 TI - Immunohistochemical study of cathepsin B. Prognostic significance in human lung cancer. AB - BACKGROUND: The concentration of cysteine proteinase cathepsin B has been shown to be elevated in association with malignancy or metastatic potential of human and rodent tumors, but its prognostic value for human lung cancer remains undetermined. METHODS: Using a polyclonal antibody, immunohistochemical analyses of cathepsin B were performed on paraffin embedded sections of tumors obtained surgically from 108 patients with non-small cell lung cancer (49 squamous cell carcinomas, 59 adenocarcinomas). The immunohistochemical expressions of cathepsin B in the tumors were compared with patient survival. RESULTS: Higher grade expression of cathepsin B was associated significantly with shorter survival in non-small cell lung cancer (P < 0.01), in squamous cell carcinoma (P < 0.05), and in adenocarcinoma (P < 0.01). A similar result also was seen in Stage I non-small cell lung cancer (P < 0.05). CONCLUSIONS: The authors concluded that the immunohistochemical staining pattern of cathepsin B may be a useful predictor of survival for human lung cancer. PMID- 8004583 TI - Acute myeloid leukemia in Manitoba. The consequences of standard "7 + 3" remission-induction therapy followed by high dose cytarabine postremission consolidation for myelosuppression, infectious morbidity, and outcome. AB - BACKGROUND: To the authors' knowledge, the natural history of myelosuppression and infectious complications associated with the use of standard cytarabine (ARA C) plus daunorubicin ("7 + 3") remission-induction therapy for adult acute myeloid leukemia (AML) and high dose ARA-C (HDARA-C) consolidation has not been described completely. METHODS: A retrospective study of untreated adult AML patients receiving standard 7 + 3 induction followed by "5 + 2" and HDARA-C consolidation was undertaken to describe the relationship of the myelosuppression profiles, blood product use, and infectious morbidity, and to correlate this finding with the outcome of antileukemic therapy. Multivariate techniques were used to evaluate variables of prognostic importance. RESULTS: Fifty-nine percent of the patients achieved remission after a median of 35 days; almost half (48%) of these patients required more than one 7 + 3 induction course. For one, two, and three induction courses, the mean number of days the patients experienced severe neutropenia (< 0.5 x 10(9)/l) were 22.5 +/- 10.9, 39.3 +/- 14.3, and 47.4 +/- 9.7 days (P < 0.001), respectively, and the infection rates were 1.45, 2.45, and 3 infections per course (P < 0.0001), respectively. The pattern of blood product use was similar. HDARA-C consolidation was the most significant factor related to prolonged disease free survival, however the myelosuppression profiles and infection rates were surprisingly similar to those for the single 7 + 3 induction courses. CONCLUSIONS: The 7 + 3 induction regimen used in this center provided only limited antileukemic activity, while requiring multiple induction courses in a high proportion of patients. The use of multiple induction courses had consequences of prolonged myelosuppression, increased blood product use, and incremental risks of infectious complications. HDARA-C consolidation for those who experienced complete remission appeared to improve disease free survival with myelosuppression comparable with that of patients who received primary induction therapy. The infection risk was acceptable, with only a marginal increase in bacteremic and fungal infections. PMID- 8004584 TI - Leukemic meningitis in a patient with splenic lymphoma with villous lymphocytes (SLVL). Meningitis as a possible initial manifestation of SLVL. AB - BACKGROUND: Splenic lymphoma with villous lymphocytes (SLVL) is a low grade, non Hodgkin's lymphoma with a stable or slowly progressive clinical course. To the authors' knowledge, central nervous system involvement has not been described previously in patients with SLVL. METHODS: Morphologic, immunocytochemical, and immunohistochemical analyses were conducted to determine the nature of villous lymphocytes in the peripheral blood, spleen, and cerebrospinal fluid (CSF) of a patient with massive splenomegaly. RESULTS: A diagnosis of SLVL was made, based on tartrate-resistant acid phosphatase-negative peripheral villous lymphocytosis with CD19+, CD20+, HLA-DR+ phenotypes, and the involvement of spleen white pulp with these cells. Mononuclear cells in the CSF showed the same morphologic and immunocytochemical features seen in the villous lymphocytes in the peripheral blood and spleen. Splenectomy and intrathecal chemotherapy were successful in clearing leukemic cells from the CSF. CONCLUSION: In this patient with SLVL in whom leukemic meningitis developed, meningitis was found to be a possible initial manifestation of SLVL. PMID- 8004585 TI - Tamoxifen administration is associated with a high rate of treatment-limiting symptoms in male breast cancer patients. AB - BACKGROUND: Although an uncommon disease, male breast cancer (MBC) will be responsible for 300 deaths in 1993 in the United States. Because of the high rate of estrogen receptor positivity in males, adjuvant hormonal therapy with tamoxifen in the adjuvant setting has been used widely. Little is known about the side effects of this estrogen receptor blocker in males. METHODS: The authors evaluated the side effects of adjuvant tamoxifen treatment in 24 patients (19 of whom were estrogen receptor positive) treated at the authors' institution between 1990 and 1993. RESULTS: Fifteen (62.5%) patients reported at least one side effect. The most common side effect was a decrease in libido, which occurred in 7 (29.2%) patients; followed by weight gain, which occurred in 6 (25%) patients; hot flashes, which occurred in 5 (20.8%); mood alterations, which occurred in 5 (20.8%); depression, which occurred in 4 (16.6%); insomnia, which occurred in 3 (12.5%); and deep venous thrombosis, which occurred in 1 (4.2%). Five (20.8%) patients terminated treatment with tamoxifen in less than 1 year because of these side effects. Two of these patients had decreased libido, two had hot flashes, and one suffered deep venous thrombosis. CONCLUSIONS: In contrast to female breast cancer patients, who have a 4% attrition rate to adjuvant tamoxifen treatment, MBC patients have a 20.8% attrition rate related to side effects of tamoxifen treatment. PMID- 8004586 TI - Effect of tamoxifen on lipid peroxide and antioxidative system in postmenopausal women with breast cancer. AB - BACKGROUND: Current evidence clearly indicates that free radicals play a prominent role in the incidence and development of breast cancer. Available literature suggests that tamoxifen is a potent suppressor of lipid peroxide formation in both animal and human systems. The purpose of this study was to understand the rate of lipid peroxidation and the status of antioxidants in tamoxifen-treated postmenopausal women with breast cancer. METHODS: A short term evaluation of 6 months' tamoxifen therapy (10 mg twice a day) in 64 postmenopausal women was conducted. The rate of serum lipid peroxidation and the status of enzymic and nonenzymic antioxidants were evaluated before and after 3 and 6 months' tamoxifen treatment. RESULTS: At 3 and 6 months' evaluation, tamoxifen-treated patients showed a significantly decreased concentration of malondialdehyde (P < 0.001), an end product of lipid peroxidation, and remarkably increased levels of enzymic and nonenzymic antioxidants. In addition to that, the concentrations of serum selenium and vitamins A, C, and E were increased significantly (P < 0.01 for each) in these patients. CONCLUSION: The results suggest that tamoxifen therapy exerts significant positive effects on the rate of lipid peroxidation and protective systems in postmenopausal women with breast cancer. PMID- 8004587 TI - Parathyroid hormone-related protein gene expression in invasive cervical tumors. AB - BACKGROUND: Parathyroid hormone-related protein (PTHrP) is the main tumor-derived factor responsible for the hypercalcemia of malignancy. METHODS: Using a polyclonal serum to the 37-67 region of PTHrP, and 35S-labeled riboprobes, the authors investigated the cellular expression of PTHrP mRNA and peptide in formalin fixed, paraffin embedded sections from 16 invasive cervical tumors. In addition, the relationship among the histologic cell type, degree of differentiation, pattern of invasion, and tumor expression of PTHrP were examined. RESULTS: PTHrP mRNA and peptide were identified in 10 of 10 and 16 of 16 tumors examined, respectively. Overall strong mRNA expression with moderate to intense intracellular staining for peptide was associated, with adenosquamous carcinoma displaying a spray pattern of invasion. CONCLUSION: PTHrP mRNA and peptide were observed in all cervical tumors studied. Despite their high frequency of expression of PTHrP, cervical tumors seldom give rise to humoral hypercalcemia of malignancy, but the autocrine/paracrine effects of PTHrP may be important in the growth and dedifferentiation of the malignant cell population. PMID- 8004588 TI - Thrombocytosis as a prognostic factor in women with cervical cancer. AB - BACKGROUND: Thrombocytosis (a platelet count > 400 x 10(9)/l) is found frequently in association with malignant disease and recently has been suggested to be a poor prognostic indicator in patients with cervical cancer. The authors decided to see if these findings could be verified. METHODS: The pretreatment platelet counts of 643 women treated for cervical cancer between 1983 and 1992 were reviewed and correlated to each patient's age, stage of disease, histologic type, node status (when available), and outcome. Differences between groups were analyzed using the chi 2 test, and survival was compared using the log rank test on Kaplan-Meier life tables. RESULTS: The 5-year survival rate for patients with thrombocytosis was 57.1%, which was significantly worse than the 76.5% for those with normal platelet counts (P < 0.01). When adjusted for stage of disease, however, thrombocytosis failed to have a significant effect on patient survival. There was also no relation between thrombocytosis and the incidence of positive lymph nodes. CONCLUSION: Thrombocytosis was not found to be an independent prognostic factor in patients with carcinoma of the cervix in this series of 643 patients. PMID- 8004589 TI - Transforming growth factor-beta inhibits proliferation of human ovarian cancer cells obtained from ascites. AB - BACKGROUND: Previously, the authors found that immortalized ovarian cancer cell lines generally were resistant to the growth inhibitory effect of transforming growth factor-beta and frequently had lost the ability to produce or activate this growth factor. In this study, the authors examined whether early passage epithelial ovarian cancer cells obtained from ascites are growth-inhibited by or produce transforming growth factor-beta. METHODS: Ovarian cancer cells were purified from ascites by percoll gradient density centrifugation, and inflammatory cells were removed using anti-CD45 antibody. The effect of transforming growth factor-beta on the proliferation of ovarian cancer cells was assessed using the thymidine incorporation assay. Immunohistochemical staining for transforming growth factor-beta 1 and beta 2 also was performed in these cells. RESULTS: Transforming growth factor-beta (10 ng/ml) significantly inhibited [3H]thymidine incorporation in 19 of 20 (95%) primary ovarian cancers (P < 0.05). In cases in which significant inhibition was seen, the mean thymidine incorporation was 33 plus or minus 28% of control values. In addition, there was no difference in dose-dependent inhibition of proliferation between ovarian cancer cells and normal ovarian epithelial cells. Eleven of 18 ovarian cancers (61%) were found to express immunohistochemically detectable transforming growth factor-beta, but immunostaining was not observed in 39% of cases. CONCLUSIONS: Although most primary ovarian cancer cells remain sensitive to the growth inhibitory effect of transforming growth factor-beta, loss of production may interrupt the transforming growth factor-beta autocrine inhibitory loop and play a role in the development of some ovarian cancers. PMID- 8004590 TI - Changing trends. An overview of breast cancer incidence and mortality. AB - The incidence of breast cancer rose about 1% per year between 1940 and 1980 according to data in the Connecticut Tumor Registry. A sharp increase of 32% was reported between 1980 and 1987 in the Surveillance, Epidemiology and End Results Program of the National Cancer Institute. Data from this program shows that the increase in incidence was due to localized cases and cancers of less than 2 cm in greatest dimension. In addition, a sharp increase in carcinoma in situ was observed. The increase in breast cancer incidence coincides with an increased use of mammography in asymptomatic women in the 1980s. Mortality from breast cancer has changed little since the 1930s, but the increases in localized and small-size tumors and decreases in the rate of tumors of 3 cm or larger at diagnosis indicates that breast cancer mortality may start to decrease. Evidence from provisional breast cancer monthly mortality data suggests that there was a 3-6% drop in 1991 compared to 1990. PMID- 8004591 TI - The relationship of breast cancer epidemiology to screening recommendations. AB - The epidemiology of breast cancer involves several factors that may be useful in deciding to recommend breast cancer screening. Paramount among these factors is age. A family history of breast cancer may be a basis for modifying screening recommendations, but this may be appropriate only for a subset of women with breast cancer in a relative. Although there are several known risk factors for breast cancer, no single factor accounts for a large proportion of disease, and many patients with breast cancer have none of the recognized risk factors. A decision to forgo screening based on the absence of any single factor other than age may not be justified by current epidemiologic knowledge. PMID- 8004592 TI - Screening: assessment of current studies. AB - BACKGROUND: A major issue in decisions regarding screening women for breast cancer concerns ages of coverage, in particular, whether routine mass screening programs with mammography should cover women aged 40-49. Interpretation of results of studies on this question is affected by differences in design, adequacy of sample size, quality of mammography, period of follow-up, and other methodologic and content issues. METHODS: Experience in eight randomized controlled trials (RCTs) conducted over the past 30 years in the United States, Europe, and Canada were assessed, and problems influencing their conclusions were considered. RESULTS: The age groups studied in these RCTs varied, from 40-64 in the Health Insurance Plan (HIP) study to 40-74 in the Swedish two-country trials. In addition, they differed in periodicity and modalities of screening, with the HIP and the Canadian National Breast Screening Study providing annual examinations with mammography and clinical breast examination, and most of the other trials scheduling longer intervals between examinations with mammography alone. Great consistency is found, however, in the results for women aged 50-69, as all of these studies showed a reduction in breast cancer mortality in this age group, suggesting about a 30% decrease. For women aged 40-49, the studies showed no benefit 5-7 years after entry and an uncertain benefit 10-12 years after entry, and only one study offered information on long term effects. Additional follow-up is needed. Adequate data are not available for women 70 and older. CONCLUSION: Public health policy on mass screening with mammography for women aged 40-49 is questionable. At this time, the emphasis should be on physicians advising women about the uncertainty of the benefits of routine mammography when referrals are being considered. PMID- 8004593 TI - Mammography quality assurance programs. AB - A quality assurance program is an integral part of a department of radiology, but certain examinations require a more specialized approach than others. The need for greater quality control in mammography was recognized by the American College of Radiology in 1987. The voluntary program developed by this organization has greatly improved the overall quality of mammography in almost three fourths of the facilities in this country. The principles of this initiative now have been adopted by various state and federal agencies, but a uniform approach has not yet been finalized. Optimally, the best aspects of all of these programs will be integrated, resulting in satisfactory image quality, acceptable dosimetry, and an appropriate level of interpretive accuracy in all mammography installations. PMID- 8004594 TI - The abnormal mammogram radiographic findings, diagnostic options, pathology, and stage of cancer diagnosis. AB - An abnormal mammogram often will detect a mass, a cluster of calcifications, or both; these findings are not pathognomonic and require a tissue diagnosis to confirm the presence of invasive cancer, in situ cancer, or a nonmalignant process. Although mammography is very sensitive, its abnormalities may be nonspecific. Ultrasound may help to distinguish a cystic mass from a solid mass. The mammographic report should be concise and not vague and must provide the referring physician with clear information as to whether the test is normal, a biopsy must be performed on the abnormality, or the abnormality will be reviewed with a repeat X-ray examination in 6-month intervals until the nature of the abnormality is determined. A common error is to palpate a breast mass that is not visible on the mammogram (false negative) and assume that the mass is not cancerous. Reasonable interpretation of a mammographic abnormality must differentiate malignant disease from a variety of benign conditions and at the same time minimize the number of biopsies performed on a mammographic abnormality that proves to be benign. Asymptomatic breast cancer may be detected mammographically when screening mammography is used; five to seven cancers should be detected in each 1000 women when initially screened, and this incidence will decrease to 0.8-3.5 cancers per 1000 women screened, depending on their age. In recent reports, the detection of an in situ, or a Stage 0, breast cancer occurred in about 25% of the women screened. The earlier the stage, the better the prognosis and the more conservative the treatment options that may be offered to the patient. Every mammographic practice must be audited for quality control. Modern computer technology may make this effort less tedious and time-consuming than it was in the past. PMID- 8004595 TI - Percutaneous large core breast biopsy. AB - BACKGROUND: Surgical excision biopsy is considered by many to be the "gold standard" for the diagnosis of breast lesions. Fine needle aspiration biopsy is used by some radiologists and other physicians in an attempt to diagnose breast lesions nonsurgically. To overcome the drawbacks associated with both of these methods, the author and his coworkers have developed the image-guided automated large-core breast biopsy method. METHODS: All biopsies are performed using either a dedicated, prone stereotactic device or high-resolution near-field ultrasound equipment for needle guidance. A "long-throw" (2.3 cm) automated core biopsy device fitted with a 14-gauge needle is used to acquire five or more core samples from each lesion for histologic evaluation. RESULTS: The ability of percutaneous, image-guided, large-core breast biopsy to provide the correct histologic diagnosis of a breast lesion is equivalent to open surgical biopsy. The cost of large-core breast biopsy is one half to one quarter that of surgical biopsy. No adverse cosmesis or mammographic pseudolesion results. CONCLUSION: In an era of increasing cost restraints in health care, it is important to identify means by which the level of patient care can be maintained or improved at lesser cost. Percutaneous large-core breast biopsy provides that opportunity in the diagnosis of breast disease and should prove to be a cost-effective, reliable, and expedient alternative to surgical biopsy. PMID- 8004596 TI - The history and the effect of the mammography quality assurance legislation in Michigan. AB - This paper describes the history of mammography quality assurance legislation in Michigan, the first of its kind in the nation. It discusses the collaboration of multiple organizations in the legislative process as well as in the implementation of it. It describes the effect of the legislation on the quality of mammography throughout the state and summarizes the lessons learned from the process, especially as they apply to the implementation of the Mammography Quality Standards Act at the national level. PMID- 8004597 TI - The timely diagnosis of breast cancer. Principles of risk management for primary care providers and surgeons. AB - Alleged delay in the diagnosis of breast cancer is one of the most common reasons for medical malpractice claims in the United States, accounting for the largest indemnity payments of any single medical condition. Although the diagnosis of breast cancer can be challenging and sometimes difficult, principles of management exist to assist health providers in pursuing a resolution of any breast complaint. Studies have shown that when litigation is pursued for alleged failure to diagnose breast cancer, multiple specialists are named in the suit. In most cases, patients filing claims of alleged failure to diagnose breast cancer are premenopausal, while the majority of women diagnosed with breast cancer are postmenopausal. This reflects, in part, the challenge of diagnosing the disease in women who have difficult clinical exams to interpret, as well as dense parenchyma on mammograms, which decreases the sensitivity of the radiograph interpretation. Principles of risk management to avoid a delay in diagnosis include (1) pursuing every breast complaint to resolution, (2) following breast cancer screening guidelines, (3) establishing an office tracking system for breast cancer screening reminders, (4) tracking results of all mammograms and follow-up studies ordered, (5) referring premenopausal women for the evaluation of any breast mass that persists through a menstrual cycle, (6) considering any asymmetrical breast finding as a cause for concern, (7) referring every woman with a breast finding on physical examination for consultation, regardless of the mammogram report, and (8) carefully documenting patient history, physical exam findings, clinical impression, and follow-up plans. PMID- 8004598 TI - Genetic epidemiology of breast cancer. AB - It has been recognized for some time that a family history of breast cancer is associated rather strongly with a woman's own risk of developing the disease. Recent segregation analyses of population-based data on familial patterns provide evidence for a rare autosomal dominant allele that increases a carrier's susceptibility to breast cancer. The estimated proportion of breast cancer patients who carry this allele declines sharply with age at diagnosis. Empirical estimates of the risk associated with particular patterns of family history of breast cancer indicate the following: (1) having any first-degree relative with breast cancer increases a woman's risk of breast cancer 1.5-3-fold, depending on age, (2) having multiple first degree relatives affected is associated with particularly elevated risks, (3) having a second-degree relative affected increases the risk by approximately 50%, (4) affected family members on the maternal side and the paternal side contribute similarly to the risk, (5) a family history of breast cancer is associated with bilateral disease, and (6) breast cancer in males is associated with breast cancer in female relatives in much the same way as is breast cancer in women. Ovarian cancer clearly has been shown to be associated with breast cancer in families, and genetic linkage has provided strong evidence for a breast-ovarian cancer gene located somewhere on chromosome 17q. At the population level, having a first degree relative with ovarian cancer may be at least as predictive of a woman's risk for developing breast cancer as is having a second-degree relative with breast cancer. Considerably weaker evidence points to a possible familial relationship between breast and endometrial cancer and between breast cancer in women and prostatic cancer in males. The clinical applications of the genetic epidemiology of breast cancer are complicated by uncertainty as to the efficacy of mammographic screening in women under the age of 50. For the vast majority of women with a positive family history, the epidemiologic evidence does provide the basis for offering considerable reassurance in that risks are not extremely high. For that rather small subgroup at exceptionally high risk, realistic estimates of the magnitude of absolute risk over the next 10-20 years may be more informative and less alarming than lifetime probabilities. PMID- 8004600 TI - Highlights of the evidence of benefit for women aged 40-49 years from the 14-year follow-up of the Breast Cancer Detection Demonstration Project. AB - Randomized breast cancer screening trials are helpful in establishing evidence of benefit when they yield statistically significant results. The results of individual randomized screening trials can vary greatly depending on the quality of the images, the frequency of screening, compliance, contamination, sample size, and the length and adequacy of follow-up. For women 40-49 years of age at entry the first randomized breast cancer screening trial, the Health Insurance Program of Greater New York (HIP), showed a statistically significant decrease of 24% in breast cancer mortality at 18 years of follow-up, virtually the same as the 23% decrease seen in women 50-59 years of age. At 10-12 years of follow-up, five of seven randomized trials have shown nonstatistical decreases in breast cancer mortality. No trials with fewer than 8 years of follow-up have shown a decrease in mortality for women 40-49 years of age; whereas seven trials have shown a decrease for women older than 50 years of age. The largest study on the screening of women aged 40-49 (93,471) was the Breast Cancer Detection Demonstration Program (BCDDP). This demonstration program was not a randomized trial but has yielded indirect supportive evidence for the screening of women aged 40-49, by comparing age group results. Three highlights of these studies are presented: (1) Mammography in the BCDDP (1970s) was improved greatly compared to that in the HIP study (1960s). Mammography detected 40% of the cancers in women 40-49 years of age in the HIP compared to 90% in the BCDDP. In women 50-59 years of age, mammography detected 60% of cancers in the HIP but 92% in the BCDDP. (2) Using annual two-view mammography plus clinical breast examination after the first screen of women 45 years of age and older, subsequent detection rates were virtually the same for all age groups. The number of women screened annually yields slightly more than two breast cancers per 1000 women, regardless of age group. (3) Similar types, sizes, stage distributions, and survival and case fatality rates were demonstrated in women aged 40-49, 50-59 and 60-69 years. PMID- 8004599 TI - Nutritional risk factors for breast cancer. AB - The observation of large differences in breast cancer rates between countries has led to the hypothesis that excessive intake of dietary fat is an important risk factor for breast cancer in women. Case-control and prospective studies, however, generally have failed to show associations between dietary fat and breast cancer risk. There therefore is only weak evidence that modest reductions in fat intake (for instance to levels of 30% of caloric intake from fat) will reduce breast cancer risk. The possible benefits of lowering fat intake to levels substantially below 30% of calories will need to be tested in a randomized trial. In the meantime, the possible roles of micronutrient imbalances and childhood nutritional factors need to be studied better. Obesity is related to breast cancer in a complex way that suggests that a hormonal correlate of excessive body weight might affect breast cancer growth and metastasis. The potential benefit of intentional weight loss as an adjunct breast cancer treatment deserves further study. Many studies have suggested that drinking alcohol, even at modest levels, might increase breast cancer risk. Because the potential benefits of modest levels of alcohol for cardiovascular disease may outweigh the risk for breast cancer, recommendations for total alcohol abstinence may be premature for women with an average breast cancer risk. Women at unusually high risk for breast cancer who have a lower-than-average risk for cardiovascular disease, however, might make an informed decision to abstain from alcohol intake. Following current dietary advice to increase the amount of fruits, vegetables, and whole grains in the diet while reducing fats is certainly prudent for women to reduce their risk of several chronic disease, but current data points to the somber conclusion that such changes probably will have little effect on breast cancer risk. PMID- 8004601 TI - Survival advantage differences by age. Evaluation of the extended follow-up of the Breast Cancer Detection Demonstration Project. AB - BACKGROUND: This study considers breast cancer survival patterns by age group among women diagnosed in the Breast Cancer Detection Demonstration Project (BCDDP) to provide insight into the nature of breast cancer and suggest a possible explanation as to why the results of the randomized clinical trials differ for women younger than 50 and those 50 or older. Based on the findings of several randomized clinical trials, there is a general consensus that breast cancer screening provides a significant benefit for women aged 50-69. From these trials, there is little evidence of a short term benefit and uncertainty regarding any long term benefit of mammographic screening for women aged 40-49. METHODS: The BCDDP was not a randomized trial, but a nationwide breast cancer screening program conducted between 1973-1980, in which all participants received annual physical and mammographic examinations. Using the BCDDP data, this study calculated 14-year breast cancer survival among 4051 women diagnosed with breast cancer between 1973 and 1980 and followed through 1988 and 1989. RESULTS: In all, 598 women died of breast cancer, resulting in an overall 14-year breast cancer survival of 83.4% (standard error = 0.007). Breast cancer survival varied by tumor type, lymph node status, tumor size, and stage at diagnosis. For most of the cases, however, both the distribution and breast cancer survival rates were similar for women aged 40-49, 50-59, and 60-69 across all prognostic indicators. Only breast cancer survival among women with invasive breast cancer who had a primary tumor 5 cm or larger or with positive lymph nodes differed by age, with women aged 60-69 at diagnosis having poorer survival. Analyses by modality of detection conducted in a subset of 2739 cases indicated that the 34.6% of the cases detected by mammography alone had the highest overall breast cancer survival rates (90.9%), while the 32.2% of the cases detectable by both physical examination and mammography had the lowest breast cancer survival (79.0%). Overall, women diagnosed with breast cancer in the BCDDP had a survival advantage if diagnosed with either a smaller tumor or no positive lymph nodes, or if their breast cancer was detected by mammography alone. For women with large tumors (> or = 5 cm), the survival was 80.8% for ages 40-49, 72.1% for ages 50-59, and 61.7% for ages 60-69. DISCUSSION: Due to the higher breast cancer survival rates among women aged 40-49 with poorer prognostic characteristics, the breast cancer survival advantage for having a smaller tumor, no positive lymph nodes, or breast cancer detected by mammography alone was lower for women aged 40-49 than women aged 50 or older at diagnosis. These differences in survival advantage may help to account for the differences in mortality by age in the randomized clinical trials. PMID- 8004602 TI - Screening for breast cancer and mortality reduction among women 40-49 years of age. AB - The recent withdrawal of screening support for women ages 40-49 years is not scientifically supported. The subgroup analyses that have been used severely compromise the statistical power of the trials. None of the trials has the statistical power to be able to provide clear proof of benefit for screening women ages 40-49 years because none of the trials involved sufficient numbers of women in these age groups. Despite having not been designed to evaluate women ages 40-49 years as a separate group, five of the eight randomized, controlled trials have demonstrated mortality reductions for these women that range from 22% to 49%. In addition, data from other nonrandomized trials show that there is no difference in survival for women ages 40-49 years than for women ages 50-59 years. The detection rate for small, early cancers, using modern mammography, is similar for women in both decades. There is no scientific reason to believe that there is a sudden change in detection or cure at age 50 years, or even at menopause. The available data suggest that women ages 40-49 years can benefit from screening, just as can women ages 50-59 years. PMID- 8004603 TI - Interventions to increase breast screening. Lifespan and ethnicity issues. AB - BACKGROUND: In spite of the fact that the value of mammography has been demonstrated, it remains underused by those in need, such as older women and minority women. A consideration of lifespan and ethnicity issues may help in designing interventions designed to overcome the barriers women may face at different stages in their lives as well as the barriers that may be most salient for minority women. METHODS: There now are reports from a number of published trials indicating the value of different kinds of interventions. Interventions can be characterized as individual-directed, system-directed, social network, or multistrategy. Although little is known about what interventions may be specifically appropriate for women in their 40s, both individual-directed and multistrategy interventions have increased use of mammography significantly among women in their 50s, 60s, and 70s, including African American women. CONCLUSIONS: Although there is a considerable distance to go before all American women are getting regular mammograms, progress is being made. Attention to developing tailored interventions sensitive to lifespan and ethnicity concerns may be helpful. PMID- 8004604 TI - Relationship of age to mammography compliance. AB - Mammography use varies by age, with older women showing decreased use. The purpose of this research was to identify variables that affect screening use within two different age groups of women, those younger than 50 and those 50 and older. Predictor variables were identified using the Health Belief Model and Theory of Reasoned Action and included susceptibility, seriousness, benefits, barriers, health motivation, control, social influence, and experiential/demographic variables. A probability sample of 581 women aged 35 and older was included for analyses. Two measures of mammography compliance were tested: compliance with American Cancer Society (ACS) guidelines for the 5 years before the study and compliance with the ACS guidelines for the year before the study. An in-home interview was conducted by graduate research assistants. Compliance rates were significantly lower for women 50 and older than they were for younger women for both the 5-year compliance and the single year of compliance. Barriers were more significant for older women. Having a mammography suggested by a health care professional was most important in the older group, indicating that less weight may be given to personal decision making by this population. Higher socioeconomic status was significant with older but not younger women. For older women, interventions need to be directed toward both the physician and the individual woman. Programs that provide knowledge and address cost issues may be the most important primary components for younger women. PMID- 8004605 TI - Influence of physician communication on newly diagnosed breast patients' psychologic adjustment and decision-making. AB - BACKGROUND: Physician-patient communication is of critical importance when a breast cancer diagnosis is made, because the emotionally overwhelmed patient must be educated about her disease and available treatments so she can participate in decisions about her care. A research study addressed the hypothesis that patients whose surgeons used psychotherapeutic techniques during the cancer diagnostic interview would have better psychologic adjustment to their cancer. METHODS: One hundred women surveyed 6 months after surgery completed the Cancer Diagnostic Interview Scale (CDIS) and the SCL-90-R, a measure of psychologic well being. RESULTS: Factor analysis of the CDIS revealed that the physician's caring attitude was perceived by the women as most important, with information-giving as a much weaker component. Multiple regression analysis supported the hypothesis that psychologic adjustment was predicted by physician behavior during the cancer diagnostic interview. Other significant predictors of adjustment were a history of psychiatric problems and premorbid life stressors. CONCLUSIONS: Provision of information needed for decision-making appears to be valued largely within the context of a caring physician-patient relationship. Specific surgeons' behaviors believed to facilitate patient adjustment include expressing empathy, allowing sufficient time for patients to absorb the cancer diagnosis, providing information, and engaging the patient in treatment decision-making. PMID- 8004606 TI - Evaluation of abnormal screening mammograms. AB - The purpose of routine screening mammography is to detect unsuspected cancer that has the potential to be cured. Abnormalities detected on the screening examination often necessitate additional radiologic workup before a definitive result or diagnosis can be given. This workup (diagnostic mammography) may include specialized views, such as spot compression to evaluate the margins of a nodule, or magnification views to determine the features of microcalcifications. Additional evaluation with mammographic views, breast ultrasound, and, at times, interventional procedures such as fine needle aspiration or core biopsy are performed to complete the radiologic evaluation of a patient with an abnormal mammogram. Signs of malignancy include nodules (most often poorly defined), microcalcifications, and, less commonly, areas of architectural distortion, asymmetry, or focal ductal dilatation. A comprehensive approach to breast imaging will help to potentiate the early detection of subtle malignancies and avoid the performance of some biopsies for benign lesions. PMID- 8004607 TI - Overview of the biology and management of ductal carcinoma in situ of the breast. AB - Ductal carcinoma in situ of the breast (DCIS) is an early, noninvasive stage of breast malignancy that arises from ductal epithelium and has an especially favorable prognosis. Its biologic characteristics are consistent with a direct precursor to invasive carcinoma, which develops in the majority of cases if left untreated, generally within 10 years of diagnosis. Mammography has resulted in a substantial increase in its diagnosis, as well as a change in its presentation from large, palpable masses to nonpalpable lesions manifested primarily as microcalcifications. The same treatment options are available for DCIS as for invasive breast carcinoma, and there is also a limited role for wide local excision alone in incidental lesions. Most cases of DCIS currently are treated effectively by lumpectomy and radiation therapy, although the fact that 50% of all local breast recurrences are invasive lesions may affect survival adversely. Mastectomy is associated with the best survival rates and should be performed on any patient with factors known to pose a high risk of locoregional recurrence. There are still many outstanding issues to be resolved by further study before the intriguing potential of this disease can be realized fully. PMID- 8004608 TI - Mastectomy from the perspective of a medical oncologist. AB - An increasing awareness of breast cancer and the increased use of mammography fortunately is resulting in a marked increase in the diagnosis of early breast cancer. Many of these lesions are characterized by intraductal breast cancer (ductal carcinoma in situ) and/or lesions smaller than 1 cm. Before the era of mammography, approximately 3-5% of new breast cancer cases involved ductal carcinomas in situ. More recent series suggest that such lesions can account for up to 25% of all new breast cancer cases. Breast conservation therapy is of particular importance to this population of patients with breast cancer. Breast conservation therapy is defined as excision of the primary breast tumor and adjacent breast tissue followed by radiation. This is referred to as lumpectomy, tumorectomy, segmental mastectomy, and quadrantectomy. Surgeons have participated in a series of clinical studies which that provided us with the progressive concept that breast cancer is not only a local but a systemic disease. These studies have shown that a modified radical mastectomy is as effective as a radical or extended radical mastectomy for the management of breast cancer. Subsequently, patients with Stage I or II breast cancer, in which the tumor size was 4 cm or smaller, appeared to do equally well when treated with either total mastectomy or lumpectomy with radiation therapy. Lumpectomy followed by radiation therapy resulted in a 5-year survival rate of 85%, compared with 76% for total mastectomy. The probability of a radiated breast remaining free of tumor at 8 years after the operation was 90%, compared to 61% for those who did not receive radiation therapy after lumpectomy. Subsequent observations indicate that lumpectomy followed by breast radiation and adjuvant chemotherapy in women with positive nodes was appropriate treatment for Stages I and II breast cancer. This manuscript describes the contraindications and indications for conservative surgery for breast cancer and the role or perioperative chemotherapy. Improved imaging techniques will allow clinicians to diagnose breast cancer at an earlier stage of its evolution and demand even more stringent conservation approaches to its management. Simple or total mastectomy and lumpectomy with radiation therapy remain viable options for the management of patients with early stage breast cancer. PMID- 8004609 TI - Selection of patients for breast conserving surgery. AB - The majority of patients with breast cancer can be treated by partial mastectomy and radiation therapy. Ineligibility for breast conservation usually is related to previous radiation or the inability to receive radiation for other reasons. For patients who can receive radiation, selection for breast conservation involves the estimation of the risk for in-breast recurrence and the ability to achieve a satisfactory cosmetic result. Multiple sites of cancer within the breast and the inability to attain negative pathologic margins on the excised breast specimen are predictive for an increased risk of recurrence. The cosmetic result is compromised by excision of large volumes of breast tissue. Although the size of the tumor is not an important consideration for in-breast recurrence, the relation of the size of the tumor, and hence the volume of tissue excised, to the size of the breast is an important cosmetic consideration. Compared to invasive ductal carcinoma, an extensive intraductal component or invasive lobular carcinoma tends to be more difficult to define within the breast and may require excision of a large volume of tissue to obtain negative pathologic margins. PMID- 8004610 TI - The Reach to Recovery program. AB - The diagnosis of breast cancer brings with it significant psychosocial concerns and questions. Part of providing comprehensive care for a woman with breast cancer requires the physician to be aware of the Reach To Recovery Program, which is a peer modeling program provided by the American Cancer Society. The women who are part of the program have had treatment for breast cancer, either a lumpectomy or mastectomy, and are trained volunteers who provide support and information for the woman diagnosed with breast cancer. The Reach To Recovery Program is a tool that can benefit both the physician and the woman who is diagnosed with breast cancer, because the Reach To Recovery volunteer can respond to the unique concerns of the woman. The concerns can include the physical, emotional, and cosmetic needs related to the disease and/or its treatment. This paper will discuss the role of the Reach To Recovery volunteer, the features and benefits of the program, and ways in which the physician can access the Reach To Recovery Program. The Reach To Recovery Program is in the process of being revised to meet the changing needs that are the result of new treatments and shorter hospital stays. Alternative types of visit patterns will be presented. PMID- 8004611 TI - Breast reconstruction. AB - Breast reconstruction after mastectomy is becoming more common despite the general trend toward breast conserving therapy with lumpectomy and radiation. Reconstruction at the time of mastectomy can be done safely and eliminates the disadvantages associated with a second operation under general anesthesia. There are also some psychologic benefits to immediate reconstruction. Autologous reconstruction with flap tissue usually is preferred by the authors. In a woman with small breasts or when autologous tissue is not available, a prosthetic reconstruction is an acceptable choice. The authors prefer the use of textured saline implants in a submuscular position. Nipple and areola reconstruction is performed at least 3 months later as an outpatient procedure under local anesthesia. In 216 consecutive patients with immediate reconstruction, the patients with autologous reconstruction with transverse rectus abdominis or latissimus dorsi flaps ranked their level of symmetry as well as their level of overall satisfaction significantly higher than did the patients with prosthetic reconstruction. Similarly, the surgeons ranked the results from the autologous reconstructions higher. In the patients who underwent autologous reconstruction, 6% had necrosis of a significant portion of the flap. Prosthetic reconstructions were complicated by infections, hematomas, and chest-skin necrosis, resulting in removal of the implant in a total of 8% of the patients in this group. Thirty four percent of the patients received adjuvant chemotherapy, and the reconstructive surgery did not result in a delay of the onset of this treatment. The authors conclude that breast reconstruction is a safe procedure with an acceptable morbidity when done either as an immediate or a delayed procedure. Patient satisfaction rates are high, particularly with autologous reconstructions. PMID- 8004612 TI - Prognostic factors in early breast carcinoma. AB - Several investigators, the SEER data, and the ECOG/Intergroup study have shown that patients with small tumors (< 0.5 cm) have a recurrence rate of less than 2%, compared to 20-25% for large tumors (> or = 5 cm). Nuclear grade and tumor differentiation are established indicators; however, the interobserver lack of concordance has thwarted their use in clinical trials. The presence of peritumoral lymphatic and blood vessel invasion (PLBI) is associated with a relative risk of recurrence of 4.7. The predictive value of the presence of hormone receptors in tumors is associated with a favorable disease free and overall survival difference of 8-10%; however, this advantage is being eroded by the early appearance of other factors, such as the epidermal growth factor receptor (EGFR), proliferative capacity (S-phase), nuclear grade, and HER-2/neu oncogene. Concordance among the different methods of hormone-receptor assay (immunocytochemical, sucrose gradient, and dextran-coated charcoal) is essential to refine the true value of these factors. DNA flow cytometry measurements of ploidy (DNA content) and S-phase fraction are the most characterized of the prognostic factors. There are conflicting reports regarding the clinical significance of ploidy status, while measurements of S-phase fraction clearly indicate a robust association with disease free and overall survival. Our data continue to show that S-phase, but not ploidy, can predict time to recurrence significantly in untreated patients, even when data are stratified for tumor size. HER-2/neu oncogene is expressed in about 50% of ductal carcinoma in situ and 14% of invasive ductal carcinoma. The presence of this oncogene at high copy number may be a useful independent marker of poor prognosis and may be associated with drug resistance and correlated with tumor recurrence and shorter survival. EGFR could be measured in most breast tumors, and the level of its expression has inversely correlated with estrogen receptor protein expression. The value of EGFR as a predictor of prognosis remains controversial and is still being investigated. Cathepsin-D provides a provocative biologic rationale but is hindered by different and incongruent methods of analysis. The majority of large studies with more than 3-years' follow-up suggests that high cathepsin-D levels may be predictive of greater recurrence and lower survival. Angiogenesis has been implicated as a critical component of the metastatic process. Early studies show that tumor angiogenesis is an independent and highly significant prognostic indicator, and its presence may suggest the selection of "anti-angiogenic therapy."(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8004613 TI - Adjuvant systemic therapy for early breast cancer. AB - The results of an overview of all randomized clinical trials has demonstrated that the use of adjuvant chemotherapy for younger or premenopausal women will reduce their annual odds of death by about 25%. The use of adjuvant tamoxifen in older or postmenopausal women, especially those with estrogen receptor-positive tumors, will have a similar effect. The absolute survival of patients with positive nodes at the end of 10 years will be between 8% and 10%. This does not mean necessarily that 8-10% of patients will be cured, and a more accurate description of the benefits of adjuvant therapy might be expressed as the average prolongation of life. This number is not as easily obtained. Differences in median survival between treated and untreated patients is approximately 2 years, and this might be taken as an approximation of the average increase in survival these patients will derive from adjuvant treatment. The proportional reduction in the odds of recurrence or death among women with negative nodes is identical to that of women with positive lymph nodes, but the absolute differences always will be greatest among those with the greatest risk of recurrence. Therefore, the use of adjuvant tamoxifen will result in a greater survival benefit for women with many positive nodes than for those with negative nodes. PMID- 8004614 TI - Quality-of-life research in patients with breast cancer. AB - Quality-of-life evaluation has gained increasing attention within the oncology community over the past 2 decades. The breadth of quality-of-life research in women with breast cancer has expanded substantially during this time. This paper reviews the status of quality-of-life research in women with breast cancer and explores several areas in which quality-of-life research can be of value. Descriptive quality-of-life studies in patients undergoing active treatment can identify the impact breast cancer treatment has on a patient's life. For patients who have completed treatment, research can detect areas of persistent distress. Quality-of-life assessment now is incorporated in many clinical trials. These data can provide a patient-rated assessment of treatment and complement the traditional endpoints in clinical trials. Examples of selected quality-of-life studies in patients with breast cancer are presented. PMID- 8004615 TI - Multidisciplinary management of advanced primary and metastatic breast cancer. AB - Combined modality therapy has become the treatment of choice for patients with primary breast cancer, including those with locally advanced breast cancer. Primary or induction chemotherapy, followed by surgery or radiation therapy or both, and adjuvant systemic therapy is a generally accepted strategy. Most tumors respond with a more than 50% decrease in tumor size, and approximately 70% of patients experience down-staging through primary chemotherapy. Breast conservation is possible for many patients with locally advanced breast cancer, and almost all patients initially are rendered disease free. Primary chemotherapy should be the initial choice of treatment for patients with locally advanced tumors, but it is unclear what the optimal sequence of subsequent therapies should be, or whether one or two local treatment modalities are necessary. The most dramatic example of the efficacy of these regimens was demonstrated in patients with inflammatory breast cancer. Previously a universally fatal condition, the natural history of this disease has been changed dramatically by the introduction of these combined modality therapies. Five-year survival rates of 35-60% commonly are reported, and it is likely that about one third of patients with this highly aggressive form of disease will survive beyond 10 years without recurrence. Combined modality therapy that includes primary chemotherapy provides appropriate local control, the possibility of breast conservation therapy, and, probably, an increased survival rate, at least for some subsets of patients with locally advanced breast cancer. The use of similar treatment strategies for early breast cancer is currently under evaluation. Hormone therapy and combination chemotherapy represent the main treatment approaches to metastatic breast cancer. Radiotherapy is also a useful palliative tool, especially for control of painful bone metastases and central nervous system involvement. Patient and tumor characteristics help in the optimal selection of systemic therapy. Palliative therapy for symptomatic control and prolongation of life also preserves a good quality of life. Dose-intensive chemotherapy is being evaluated as a treatment to increase complete response rates and cause remission consolidation. Clinical trials on several new and effective cytotoxic agents, as well as new hormonal compounds, are being completed and are showing encouraging preliminary results.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8004616 TI - Involution and the etiology of breast cancer. AB - Because of the recognized relationship between aging and the development of cancer, the authors have proposed that the rate and extent of involution may be important factors in the etiology of breast cancer. They further have examined existing epidemiologic and histopathologic data to evaluate the possible association between abnormal involution and breast cancer risk. Evidence for the association is largely circumstantial, because studies have not been designed specifically to evaluate the relationship between the process of involution and breast cancer. Until studies are performed to compare histopathologically the extent of involution in breast cancer patients and age-matched controls, the role of involution in the etiology of breast cancer will remain uncertain. PMID- 8004617 TI - Selection criteria for breast conservation. The impact of young and old age and collagen vascular disease. AB - BACKGROUND: Selection criteria applicable to women desiring breast-conserving surgery and radiation for early invasive breast cancer have evolved over the last decade. The presence of active collagen vascular disease has emerged as a contraindication for this treatment. The roles of both young and old age have been debated by many authors, although a growing body of literature supports the impact of age on both local control and disease free survival. METHODS: This is a review of the literature addressing these selection criteria. RESULTS: A consensus exists regarding the impact of preexisting collagen vascular disease on the anticipated complications with breast-conserving radiation, despite small numbers reported. A young age, although not always a statistically significant factor, emerges as a consistent predictor for both local and distant failures. This is true not only for patients who opt for breast conservation but also those who are treated with mastectomy. To the contrary, preliminary data suggests that older age is emerging as a predictor for improved local and regional control. CONCLUSIONS: Preexisting collagen vascular disease is a contraindication for the use of breast-conserving radiation and surgery. Extremes of age must be considered in terms of recommending not so much a specific local regional treatment, but an overall strategy. For the very young patient with breast cancer, more aggressive systemic therapy should be considered in addition to the appropriate local regional therapy. For the elderly, preliminary pilot studies suggest that tamoxifen may play a role in local as well systemic control, perhaps opening the door for future trials examining the need for radiation in selected elderly patients. PMID- 8004618 TI - Breast reconstruction. Surgical options and patient selection. AB - Breast reconstruction has undergone a steady evolution since the introduction of the silicone gel prosthesis in the early 1960s. Current restrictions of the use of breast implants have increased the reliance on autologous tissue reconstruction. The improvement in the quality of breast reconstruction can be attributed in part to a refinement in mastectomy technique. There is an increasing emphasis on skin preservation, which makes it easier to match the remaining breast. In this paper, various methods, including tissue expansion, the latissimus dorsi flap, the transverse rectus abdominis musculocutaneous flap, and free flaps, are described. The indications as well as potential complications for each methods also are discussed. Local recurrence after breast conservation generally necessitates a total mastectomy. Radiation fibrosis and endarteritis interfere with skin blood supply and impair wound healing. Reconstruction in this setting has a potential for increased operative morbidity. Treatment options, including techniques to reduce potential complications, are presented. PMID- 8004619 TI - Autogenous tissue breast reconstruction in the silicone-intolerant patient. AB - BACKGROUND: Concerns regarding the safety of silicone gel breast implants have motivated many patients with complications from their silicone breast implants to search for alternatives for breast reconstruction. Although autogenous tissue has been used for primary breast reconstruction after mastectomy, few studies have described its use in the patient in whom silicone-implant breast reconstruction has failed. METHODS: Between 1988 and 1993, 33 patients who had previous unsuccessful breast reconstruction with silicone breast implants underwent implant removal and autogenous tissue reconstruction. Preoperative evaluation included implant-related problems, such as capsular contracture, pain, and loss of implant shell integrity. Systemic symptoms that developed after implantation also were evaluated. Three types of myocutaneous flaps were used for breast reconstruction: the latissimus dorsi pedicle flap, the transverse rectus abdominis free flap, and the superior gluteus maximus free flap. Follow-up evaluation was done for both implant-related problems and issues related to patient satisfaction after autogenous tissue reconstruction. RESULTS: The overall flap survival rate for 33 women who underwent flap reconstruction was 94%. All flap losses occurred in the first nine flaps. Ninety-two percent of patients felt their autogenous tissue reconstructions were aesthetically superior to their previous implant reconstruction. All but one patient felt complete resolution in their chest wall discomfort and pain. Eighty-one percent of patients with systemic symptoms also felt improvement in their systemic symptoms. CONCLUSIONS: Autogenous tissue reconstruction from multiple areas of the body is an effective and aesthetically superior alternative for the patient who no longer desires the silicone implant option. PMID- 8004620 TI - The role of radiation therapy in the multidisciplinary management of recurrent and metastatic breast cancer. AB - Carcinoma of the breast is a disease that is associated with 10-year recurrence rates of 25% in operable patients with no spread to the axillary nodes and 75% in patients in whom the tumor has extended to the axillary nodes. Locoregional recurrence rates of close to 50% have been reported in patients with Stage III disease. Adjuvant prophylactic postoperative irradiation can reduce locoregional recurrences to less than 10%. When locoregional recurrence occurs after mastectomy, therapeutic irradiation is required. It can achieve tumor control in at least 50% of cases. The best conditions exist when a surgical procedure can achieve gross removal of the recurrent tumor before irradiation and when the fields of irradiation encompass the chest wall and pertinent lymph node areas. The required dose of radiation is lower after excision of the tumor, and the chances of local tumor control are higher. The dose of radiation must be 4500 5000 cGy (fractions of 180-200 cGy) to the subclinical disease and a boost of 1000-1500 cGy added to the known tumor areas. Distant metastatic manifestations must be dealt with for palliative purposes, except in the case of isolated supraclavicular metastasis, where radical irradiation can achieve cure. The need exists for a definition of the role of systemic therapy for locoregional recurrence, and for the development of the optimal integration of systemic chemotherapy and local radiotherapy in patients with locoregional or distant breast cancer recurrences. PMID- 8004621 TI - Management of locally advanced carcinoma of the breast. I. Noninflammatory. AB - BACKGROUND: The treatment of patients with locally advanced noninflammatory breast cancer has evolved substantially over the past 30 years. From 1968 to 1989, 281 women were treated at Mallinckrodt Radiation Oncology Center with four different treatment methods. Median follow-up was 6.2 years (range 3-22 years); no patient was lost to follow-up. METHODS: Retrospective review of records and analysis of data on a computer file were carried out. Thirty-five patients were treated with irradiation alone, 33 with irradiation and adjuvant chemotherapy, 81 with mastectomy and irradiation, and 132 with mastectomy, irradiation, and chemotherapy (triple-modality). RESULTS: Actuarial 5- and 10-year disease free survival (DFS) rates were 45% and 36%, respectively, with triple-modality therapy, 31% and 10% with irradiation and chemotherapy, 32% and 19% with irradiation and mastectomy, and 19% and 11% with irradiation alone. Cause specific survival (CSS) paralleled DFS in the four groups. Locoregional tumor control at 5 years was 91% for irradiation, mastectomy, and chemotherapy, 80% for irradiation and mastectomy, 54% for irradiation and chemotherapy, and 31% for irradiation alone. Systemic therapy and/or irradiation given before mastectomy yielded better locoregional tumor control, DFS, and CSS (not statistically significant). No difference in results was noted with radical, modified radical, or total mastectomy. In the triple-modality group, no chest wall failures occurred with chest wall doses greater than 5040 cGy. Grade 2 or higher treatment sequelae were noted in 10-42% of patients, depending on treatment modality. CONCLUSIONS: Triple-modality therapy yielded improved locoregional tumor control, DFS, and CSS compared with other modalities. Patients treated with surgery had better locoregional tumor control than those who received irradiation alone or in combination with chemotherapy, but the impact on DFS and CSS was less impressive. Additional clinical trials are needed to define further the role and optimal use of the various therapeutic modalities in the management of locally advanced breast cancer. PMID- 8004622 TI - Management of locally advanced carcinoma of the breast. II. Inflammatory carcinoma. AB - BACKGROUND: Inflammatory carcinoma of the breast has been associated with a poor prognosis. Several therapeutic approaches have been under investigation in an effort to improve outcome. METHODS: This is a retrospective analysis of 179 patients with histologically confirmed inflammatory carcinoma of the breast: 33 treated with irradiation alone, 35 with combined irradiation and chemotherapy, 25 with irradiation and surgery, and 86 with a combination of three modalities. RESULTS: The 5-year disease free survival (DFS) rates were 40% for patients treated with three modalities, 24% for those treated with irradiation and surgery, and 6% for those treated with irradiation alone or in combination with chemotherapy without a surgical procedure. The 10-year DFS rates were 35%, 24%, and 0%, respectively. Cause specific survival (CSS) curves closely follow the same trends. A clearly superior locoregional tumor control was observed in patients who underwent a surgical procedure: 79% with three modalities, 76% with irradiation and surgery, and only 30% with irradiation alone or in combination with chemotherapy. Distant metastasis occurred in 57% of the group treated with triple-modality therapy, 60% of those treated with irradiation plus surgery, and 85% of the patients treated with irradiation alone or in combination with chemotherapy. There was no significant correlation between the type of mastectomy or doses of irradiation and locoregional tumor control or survival. The significant morbidity of the trimodal therapy (10%), although somewhat higher than that of other modalities (3.2%), was acceptable. CONCLUSIONS: The addition of mastectomy to irradiation significantly improved locoregional tumor control, DFS, and CSS; differences were statistically significant. The combination of chemotherapy, surgery, and irradiation had a significant impact on locoregional tumor control and incidence of distant metastases compared with surgery plus irradiation, and a lesser impact, although still statistically significant, on DFS and CSS. Further clinical trials are needed to optimize the management of patients with inflammatory breast cancer. PMID- 8004623 TI - Postmastectomy radiotherapy in the management of operable breast cancer. AB - There is a long and detailed history of radiation therapy as an adjuvant to surgery in operable breast cancer. The results of a large number of randomized clinical trials will be reviewed. They can be summarized by saying that although the trials show a reduction in local-regional failure with the use of postoperative radiotherapy, a survival advantage has not been clearly identified. Many of the older trials used techniques and radiation doses inadequate by current standards, which may have affected the results. Recent trials that used therapeutic doses of radiation, however, did demonstrate a survival advantage among patients who received postoperative radiotherapy. These trials generally have included chemotherapy and required careful integration of radiotherapy and systemic therapy. Although all trials have not demonstrated a survival benefit by the addition of radiotherapy, the ability to maintain local-regional control after mastectomy is an important goal. Administration of prophylactic chest wall and nodal radiotherapy to patients at high risk for local-regional recurrence significantly reduces the chance of a local treatment failure. Because a chest wall recurrence is a distressing event that dramatically affects quality of life, improved local-regional control with postoperative radiotherapy is a highly significant end point. PMID- 8004624 TI - Breast cancer evaluation. Medical-legal and risk management considerations for the clinician. AB - The legal consequences for physicians involved in the treatment of patients who are at risk for or have developed breast cancer are many. The law of negligence, which is concerned with departures from reasonable standards of conduct, govern most of the cases that come to legal attention. Several other torts or civil infractions, however, may be applicable to such practices. Lessons learned from both trial and appellate decisions rendered in this field offer some guidance to avoid untoward medical and legal consequences. PMID- 8004625 TI - Breast cancer. Selected legal issues. AB - Several legal and ethical issues may arise during the course of screening for and diagnosis and treatment of breast cancer. Among the most active legal areas are reimbursement for therapies deemed experimental by certain insurance companies, such as high dose chemotherapy/autologous bone marrow transplantation (HDCT/ABMT) and off-label drug use; these reimbursement issues are discussed. Legal issues in mammography screening and insurance coverage and legal issues relative to informed consent in breast cancer treatment also are discussed. PMID- 8004626 TI - Supplemental estrogen replacement. AB - In the current aging society, more than 30 million women have an average postmenopausal life expectancy of 28 years. Coronary heart disease is the leading cause of death in older women, and osteoporosis results in an estimated 1.5 million fractures per year. Various studies have suggested that postmenopausal estrogen-replacement therapy could reduce the morbidity and mortality associated with these conditions. Given the uncertainty about hormone interactions and the molecular genetics of breast cancer, it seems unwise to inject yet another element into the prognostic equation, and currently it is not recommended that estrogen-replacement therapy be used routinely in patients who have been treated successfully for breast cancer. The final decision, of course, rests with the patient and her treating physicians and is subject to medical/legal interpretation. PMID- 8004627 TI - Breast cancer during pregnancy. AB - Breast cancer during pregnancy involves a host of psychosocial, ethical, religious, and legal considerations, as well as medical multidisciplinary decisions. Treatment modalities. Breast or chest wall radiation therapy should be avoided because the fetal dose, regardless of the trimester, can cause permanent complications. In the second and third trimester, chemotherapy is associated with intrauterine growth retardation and prematurity in approximately half of the infants; the risk of birth defects is a concern during the first several weeks. Typical anesthetic agents readily reach the fetus but are not known to be teratogenic. Modified radical mastectomy without delay is the best option in pregnant patients with Stage I or II and some Stage III cancer. Although abortion allows full treatment to the mother, it is not known whether the procedure is therapeutic. Early in pregnancy abortion deserves strong consideration. Prognosis. The poor prognosis of pregnancy-associated breast cancer in the past probably is attributable to a combination of initial delay and possibly to the unfavorable biologic characteristics of pregnancy. When pregnant patients are matched stage for stage with control subjects, survival seems equivalent, although pregnant patients have more advanced stage disease. PMID- 8004628 TI - Pregnancy safety after breast cancer. AB - Many more young breast cancer patients will be seeking medical advice about pregnancy, because oophorectomy is no longer performed adjuvantly, and more women are bearing children in later years. In the meager amount of literature on the topic, it has been observed that breast cancer patients who subsequently become pregnant have as good a survival rate as those with no subsequent pregnancy. In particular the case-matching studies attempt to eliminate the obvious factor of pregnancy occurring only in those with a good prognosis. Survival in cases with subsequent pregnancy is reported in some studies as better than in the controls with no posttreatment pregnancy. All reports are retrospective, are composed of small numbers of patients, were gathered over several decades, and rely on clinicians' memories, because subsequent pregnancy has not been recorded systematically. For example, the largest study includes 136 patients accumulated over 50 years. Assuming that only a small percentage of fertile breast cancer patients become pregnant, the majority appear to have been "lost to follow-up" and unreported. In summary, the limited literature on pregnancy subsequent to breast cancer does not allow one to be certain about its effect. Regarding advice to the individual patient who has decided to become pregnant, most clinicians traditionally have recommended a delay of 2 years or more to allow aggressive disease to become manifest. PMID- 8004630 TI - Theory as vision: a framework for expressing Christian values in nursing action. PMID- 8004629 TI - High dose chemotherapy with autologous stem cell support for the treatment of metastatic breast cancer. AB - The overall median survival of women with advanced or high risk primary disease has not changed with conventional chemotherapy. Regimens employing high dose chemotherapy with autologous stem cell support (ABMT) have been developed with the hope of optimizing tumor response and increasing survival. Early Phase I studies of patients with advanced refractory disease demonstrated the feasibility of administering agents in doses 5-30 times higher than those conventionally used. These studies achieved high response rates of short duration. Second generation studies combined an induction phase followed by one high dose intensification at the time of maximum tumor response. To date, between 15 and 30% of women with metastatic disease remain progression free after being treated with this approach, with median lengths of follow-up approaching 36 months in the larger series. With the advent of hematologic support, such as blood stem cells and colony stimulating factors, the morbidity, mortality, and costs associated with this treatment have been reduced substantially. These supports now allow for two or more cycles of high dose intensification to be employed, to exploit the potential of dose intensity to optimize response. Recent single-institution studies using ABMT for high risk Stages II and III breast cancer have reported preliminary findings suggesting a prolonged disease free survival. The cooperative groups now have begun prospective randomized studies in high risk women with Stages II and III disease with 10 or more positive axillary lymph nodes, and soon will study the efficacy of ABMT in women with inflammatory or locally unresectable breast cancer (Stage IIIB). PMID- 8004632 TI - Why use scriptures with patients? PMID- 8004631 TI - God's word--what does it mean to me as a Christian nurse? PMID- 8004633 TI - History in nursing: Alice Gallaudet Howard. PMID- 8004634 TI - Enzymic synthesis of N-acetyllactosamine on a soluble, light-sensitive polymer. PMID- 8004635 TI - The structure of the capsular polysaccharide from Klebsiella K43. AB - The structure of the capsular polysaccharide from Klebsiella type K43 has been investigated using sugar and methylation analysis, uronic acid degradation, and NMR spectroscopy on the native and the O-deacetylated polysaccharide. It is concluded that the polysaccharide is composed of pentasaccharide repeating units with the structure [formula: see text] The polysaccharide contains approximately 0.4 equiv of O-acetyl group per repeating unit, located at a primary position. PMID- 8004636 TI - Effect of modifying histidine residues on the action of Bacillus amyloliquefaciens and barley-malt alpha-amylases. AB - Modification of porcine pancreatic alpha-amylase (PPA) and Taka-amylase A(TAA) with diethyl pyrocarbonate (DEP) causes activation of the release of p nitrophenol from p-nitrophenol alpha-maltoside (G2PNP), and a decrease in amylase activity (hydrolysis of alpha-1,4 glucosidic bonds in starch). Among the possible sites of modification, attention focuses on three histidine residues present around the active site of alpha-amylases of many different origins. In PPA these are His 101, His 201, and His 299, with His 101 and His 299 being very close to the site of catalysis and thus perhaps directly or indirectly involved in the catalysis. On the other hand, His 201 is located on the aglycon side of the catalytic site, and we have suggested that it is involved in the increase of PNP release after chemical modification. Investigations of site-directed mutagenesis of the histidine residues of human pancreatic alpha-amylase support this identification. Although the degree of sequence similarity among alpha-amylases of different origins is low, there are several conserved short regions. Most belong to the structural components of the active site in PPA and TAA. Furthermore, there is a close similarity in the three-dimensional structures of PPA and TAA. The conserved residues around the active site in all alpha-amylases suggest some universal structural similarities in these active sites. Therefore, we examined the effects of the chemical modification of histidine residues in Bacillus amyloliquefaciens alpha-amylase(BLA) with DEP and made a comparison with modification of barley alpha-amylase isoenzyme II(BAII), using identical substrate systems. These two alpha-amylases have more substrate binding subsites than PPA and TAA, and have similar action patterns with malto-oligosaccharides. PMID- 8004637 TI - X-ray and conformational investigation of 6-deoxy-6-C-(1,5-di-O-acetyl-2,3-O- isopropylidene-beta-D-allo-pentofuranos-5-yl)-1,2:3,4-di-O-isopro pylidene-alpha D-galactopyranose and 6-C-(benzyl 5-deoxy-2,3-O-isopropylidene-beta-D- ribofuranosid-5-yl)-1,2:3,4-di-O-isopropylidene-D-glycero-alpha-D-galac to hexopyranose. AB - The structures of the title compounds (2b and 3) have been investigated in the solid state by X-ray methods. The crystals of 2b are monoclinic, space group P2(1), and of 3 orthorhombic, space group P2(1)2(1)2(1). The cell dimensions are: for 2b, a = 9.910(2), b = 11.745(1), c = 11.810(3) A, beta = 97.32(1) degrees; and for 3, a = 6.103(1), b = 15.954(1), c = 28.855(3) A. Both structures were solved by direct methods, and refined by a full-matrix, least-squares procedure giving for 2b, R = 0.0541 (unit weight), and for 3, R = 0.0451 (RW = 0.0445). The galactopyranose rings of 2b and 3 adopted a twist and a mixed twist-screw conformation, respectively. The absolute configuration at C-7 in 2b, as well as at C-6 in 3, was determined to be (R). Relatively strong intermolecular hydrogen bonds were observed in the crystal structure of 3. PMID- 8004638 TI - Nuclear magnetic resonance and conformational investigations of the pentasaccharide of the Forssman antigen and overlapping di-, tri-, and tetra saccharide sequences. AB - The 1H and 13C NMR parameters, i.e., chemical shifts and coupling constants, for the pentasaccharide of the Forssman antigen and overlapping di-, tri-, and tetra saccharide sequences thereof have been measured and assigned completely using 1D and 2D techniques, and the oligosaccharide structures have thereby been confirmed. Nuclear Overhauser effect (NOE) experiments have been carried out at three different temperatures to assess the preferred conformations of the pentasaccharide and the component oligosaccharides. The conformational preferences of the compounds mentioned above have subsequently been investigated by theoretical calculations. The flexibility and dynamics of the molecules have been studied by Metropolis Monte Carlo simulations using a modified HSEA force field, and ensemble average data have been generated and compared to data obtained experimentally. PMID- 8004639 TI - Synthesis of the methyl thioglycosides of 2-, 3-, and 4-deoxy-L-fucose. AB - Methyl thioglycoside derivatives of 2-, 3-, and 4-deoxy-L-fucopyranose have been prepared as glycosyl donors for the synthesis of sialyl Le(x) ganglioside analogues containing modified alpha-L-fucopyranose residues. Reductive dethioacylation of 2-(trimethylsilyl)ethyl 3,4-di-O-benzoyl-2-O (phenoxy)thiocarbonyl-beta-L-fucopyranoside, prepared from L-fucose in eight steps, gave the 2-deoxy compound, which was transformed via selective removal of the 2-(trimethylsilyl)ethyl group, subsequent acetylation, and displacement of the 1-acetoxy group by a methylthio group, into methyl 3,4-di-O-benzoyl-2,6 dideoxy-1-thio- alpha,beta-L-lyxo-hexopyranoside (11). 2-(Trimethylsilyl)ethyl 2,4-di-O-benzoyl-3-O-(phenoxy)thiocarbonyl-beta- L-fucopyranoside, prepared from the unsubstituted glycoside in four steps, and 2-(trimethylsilyl)ethyl 2,3-di-O benzoyl-4-O-(phenoxy)thiocarbonyl-beta-L-fucopyranoside, similarly prepared in two steps, were transformed via reduction of the (phenoxy)thiocarbonyloxy group, selective removal of the 2-(trimethylsilyl)ethyl group, O-acetylation, displacement of the 1-acetoxy group by a methylthio group as described for 11, and finally replacement of the benzoyl groups by benzyl groups, into the analogous, protected methyl 3- and 4-deoxy-1-thio-beta-L-fucopyranosides. PMID- 8004640 TI - Synthesis of deoxy-L-fucose-containing sialyl Lewis X ganglioside analogues. AB - Sialyl Lex ganglioside analogs containing 2-, 3-, and 4-deoxyfucose in the place of L-fucose have been synthesized. Glycosylation of 2-(trimethylsilyl)ethyl O-(2 acetamido-4,6-O-benzylidene-2-deoxy-beta-D-glucopyranosyl)-(1-->3)- 2,4,6-triO benzyl-beta-D-galactopyranoside with the methyl 1-thioglycoside derivatives of the respective deoxyfucoses, using dimethyl(methylthio)sulfonium triflate (DMTST) as a promoter, gave the corresponding three protected 2-(trimethylsilyl)ethyl dideoxy-alpha-L-heoxpyranosyl-(1-->3)- O-2(acetamido-2-deoxy-beta-glucopyranosyl) (1-->3)-beta-D-galactop yranosides. These were transformed by reductive ring opening of their benzylidene acetal groups into the glycosyl acceptors 6, 8, and 10. Dimethyl(methylthio)sulfonium triflate promoted glycosylation of 6, 8, and 10 with methyl O-(methyl 5-acetamido-4,7,8,9-tetra-O-acetyl-3,5-dideoxy-D-glycero alpha- D-galacto-2-nonulopyranosylonate)-(2-->3)-2,4,6-tri-O-benzoyl-1-th io-beta D-galactopyranoside afforded the desired pentasaccharides, which were converted via reductive removal of their benzyl groups, O-acetylation, selective removal of the 2-(trimethylsilyl)ethyl group, and reaction with trichloroacetonitrile, into the corresponding alpha-trichloroacetimidates 14, 18, and 22. Glycosylation of (2S,3R,4E)-2-azido-3-O-benzoyl-4-octadecene-1,3-diol with 14, 18, and 22 in the presence of boron trifluoride etherate afforded the expected beta-glycosides, which were transformed in good yields, via selective reduction of the azido group, coupling with octadecanoic acid, O-deacylation, and deesterification, into the target compounds. PMID- 8004641 TI - [Predictive value of various echocardiographic parameters of systolic and diastolic function in the development of congestive heart failure after infarction]. AB - To evaluate the predictive value of systolic and diastolic left ventricular (LV) function parameters, in the development of congestive heart failure (CHF) after acute myocardial infarction (AMI), 48 patients (mean age 56.2 +/- 10.4 years) were studied with two-dimensional and Doppler echocardiography (2D echo) in the acute phase (36 +/- 12 hours) and after 6 months of follow-up. The following parameters have been evaluated: LV wall motion score-index; peak velocity of early diastolic filling (E); peak velocity of filling during atrial systole (A); the ratio A/E; percent of LV filling contributed by atrial systole (A%). During follow-up 10 patients (Group B; 21%) developed symptoms and/or signs of CHF, while 38 patients (Group A; 79%) did not. In the patients who developed CHF 2D echo showed a depressed contractile function (mean value of wall motion score index 3.08 +/- 0.45 versus 3.53 +/- 0.32 of Group A; p < 0.001) and a marked impairment of filling during atrial systole: A/E = 1.89 +/- 0.80 versus 1.07 +/- 0.35 (p < 0.001); A% = 52.2 +/- 9.9 versus 39.1 +/- 8.4 (p < 0.001). The multivariate analysis showed that the ratio A/E, A% and the wall motion score index are the only variables that may predict the development of CHF. This capacity has been confirmed also considering the cut-point as conditional variables (A/E > 1.4; A% > 45%; score-index < 3.1). Our results demonstrate that a combined evaluation by 2D echo of systolic and diastolic LV function parameters allowed a better stratification of patients at risk of developing CHF after an AMI. PMID- 8004642 TI - On-line assessment of left ventricular function by automatic border detection echocardiography during rest and stress conditions. AB - A new echocardiographic system, automatic boundary detection (ABD) echocardiography, provides automatic on-line quantification of the left ventricular cavity area. To assess the potential of ABD echocardiography in measuring left ventricular dimensions and detect stress-induced changes in left ventricular function, we studied 25 patients. Thirteen were studied to compare left ventricular cavity areas and fractional area change by using 2DE and ABD echocardiography during routine studies in multiple views; 12 patients were studied during transesophageal atrial pacing by ABD-echocardiography in 4-chamber or short-axis views. End-diastolic and end-systolic left ventricular areas measured by ABD echocardiography were not significantly different from two dimensional ones for all the echocardiographic views, except the apical 4-chamber view; fractional area change values obtained with ABD were slightly lower than 2DE ones, although not significantly. High correlation values were found between the 2 techniques for end-diastolic area (r = 0.94, SEE = 3.69 cm2), end-systolic area (r = 0.90, SEE = 4.49 cm2) and fractional area change (0.73, SEE = 9.7%); similar results were obtained for each single echocardiographic view. A decrease was found from rest to peak-pacing in end diastolic area (25.2 +/- 5.1 cm2 versus 21.1 +/- 4.3 cm2, p < 0.003), end systolic area (16.2 +/- 6.0 cm2 versus 14.8 +/- 5.3 cm2, p < 0.016) and fractional area change (38.5 +/- 12.7% versus 31.8 +/- 9.6%, p < 0.003) with a return to baseline values in post-pacing (26.3 +/- 4.3 cm2 and 17.0 +/- 5.4 cm2 and 37.3 +/- 11.3%, p < 0.003 versus peak-pacing, NS versus rest for each parameter).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8004644 TI - [Effects of left bundle branch block on pulmonary vein and transmitral flow]. AB - Doppler evaluation of pulmonary venous flow (PVF) and of mitral flow (MF) can be useful to understand left ventricular function. It is well known that left bundle branch block (LBBB) can influence ventricular function. The aim of the present study was to evaluate the role of LBBB induced by ventricular pacing on cardiac performance. We performed transesophageal echocardiography (TEE) in 10 patients affected by sick sinus syndrome (SSS) treated with a permanent pacemaker (VDD modality). We evaluated PVF and MF and compared the pattern from the same patients in sinus rhythm and during cardiac pacing. We observed an increase in the reversal flow in the pulmonary vein during atrial contraction. The diastolic flow of pulmonary vein increased during cardiac pacing. The MF showed an increase in deceleration time. Our results suggest that LBBB is associated with a reduction in ventricular function. This phenomenon induce a higher contribution of atrial contraction to ventricular function. PMID- 8004643 TI - [Role of transesophageal echography in the diagnosis of aortic dissection and in therapy programming]. AB - The diagnostic accuracy of transesophageal echocardiography and its relevance on the decision making process were evaluated in 80 patients with suspected aortic dissection during a 37-month period. The diagnosis was proven by aortography and/or magnetic resonance and/or computerized tomography and/or surgery and/or autopsy in each case. Transesophageal echocardiography had no serious complication. A correct diagnosis of aortic dissection was made in 39 of 40 patients (sensitivity, 97.5%; specificity, 100%) and the type of dissection was correctly demonstrated in each case. Thrombi in the false lumen were detected in 16 patients. The primary entry site was correctly identified in 33 patients (85%). Aortic regurgitation was detected in 25 cases (severe in 9) and pericardial effusion in 14 (with tamponade in 2). Transesophageal echocardiography was more accurate than aortography in the diagnosis of noncommunicating intramural dissection (2 cases) and identified more precisely the retrograde extension of the dissection in DeBakey type III patients (4 cases). In 9 cases surgical indication was based on clinical data and transesophageal echocardiography alone. We conclude that transesophageal echocardiography allows a bedside, safe and accurate diagnosis of aortic dissection. In the majority of the patients it provides the minimal diagnostic information necessary to the therapeutical decision making. PMID- 8004646 TI - [Prevalence of microalbuminuria in recent-onset essential hypertension]. AB - To determine the prevalence of increased microalbuminuria (AER) in essential hypertension, we studied an omogeneous population comprehensive of 160 mild moderate essential hypertensives (EH) and 30 normotensive controls. All subjects underwent measurement of AER and creatinine clearance (CCl) on the 24-hour urine collection, and of plasma renin activity (PRA). The 24-hour mean arterial pressure (24h-BP) was also obtained by non-invasive ambulatory BP monitoring. The EH were subdivided into subgroups on the basis of their AER values (less or over 11 micrograms/min). Among the 160 EH the prevalence of high AER levels was of 37.5% (n = 60), showing in this subgroup of EH a mean value of 29.5 +/- 4 micrograms/min. Moreover, in the whole population of 160 EH, AER was significantly correlated to 24h-diastolic BP (p < 0.05). The subgroup of 60 EH with AER > 11 micrograms/min showed also Ccl values higher than the other subgroup of EH (p < 0.02), while non significant differences between age, mean duration of EH, PRA, and 24h-BP, both systolic and diastolic, were observed. Our results lead to hypothesize that in essential hypertension there exists a subgroup of subjects characterized, in the early phase of disease, by high capillary glomerular pressure, GFR and microalbuminuria values. PMID- 8004645 TI - [Effects of verapamil on left ventricular mass and diastolic function in hypertensive patients]. AB - To evaluate the effects of antihypertensive therapy with verapamil on left ventricular (LV) mass, systolic and diastolic function, 12 hypertensive patients, mean age 44 years, were studied during 12 months of treatment with verapamil, in a gradual release from (240-480 mg/day), by serial recordings of ECG, blood pressure (BP) and echocardiogram. In pretreatment conditions, 8 patients showed LV hypertrophy and 2 patients impaired LV diastolic function. Blood pressure decreased significantly after 1 month of therapy, septal and LV posterior wall thickness after 3 months and LV mass after 6 months. No significant changes were observed in LV fractional shortening and diastolic transmitral flow. At the end of the study BP normalized in 8 patients and LV mass in 1 patient. Left ventricular diastolic function was normalized in 1 patient but became worse in another, in spite of the reduction in BP and LV mass. Thus, verapamil was an effective antihypertensive drug and was able to revert hypertensive LV hypertrophy. However, the behaviour of LV diastolic function seems to be independent of the effects of the drug on BP and LV mass. Further studies are necessary to clarify this problem. PMID- 8004647 TI - [Coding and identification of heart failure]. AB - The prevalence of the diagnosis of heart failure (HF) presents large differences, comparing the data of hospital discharge obtained from USA and Italy through te code 428 of ninth revision of International Classification of Diseases (ICD-9). As possibly the difference is related to classification, we reviewed homogeneous diagnosis in Padua General Hospital as a whole and the diagnosis at discharge in the department of Cardiology of the same hospital. Hospital HF discharge rate is on average 0.43% (0.37-0.51); while from department of Cardiology is on average 0.7% (0.15-0.85). Medical records of a group of patients (the first hundred of 1992) are analysed and recorded using the Boston criteria for scoring the certainty of HF diagnosis. The group with unlikely HF (68%) does'nt codes 428; there is 2 code 428 in group with possible (16%) and 2 in group with definite (16%) diagnosis of HF. The physician probably prefers sometimes an anatomical rather than a functional classification and therefore he underscores the impairment of left ventricular systolic function. A better code-use is needed before comparing prevalence rate from different centres. PMID- 8004649 TI - [Early papillary muscle rupture in myocardial infarction, diagnosis with transesophageal echography]. AB - We describe the case of posterior papillary muscle (PPM) rupture with severe mitral regurgitation at the very beginning of an inferior myocardial infarction (MI) in a 79-year-old woman. The diagnosis was made by transesophageal echocardiography (TEE) and confirmed at autopsy. This case confirms the value of TEE in diagnosing PPM rupture and the association of PPM rupture with small posterior myocardial infarction. Moreover the case presents some unusual aspects: the rupture occurred very early; at transthoracic approach, a systolic convergence flow zone was the only sign of mitral regurgitation by color flow mapping; at TEE flail mitral leaflets were absent; in systole, the trunked papillary muscle did not prolapse into the left atrial cavity, but crushed into the atrial side of posterior mitral leaflet, remaining at the atrioventricular level; at autopsy, there was a split PPM with a completely ruptured medial branch. On the atrial side of the posterior mitral leaflet there was an ecchimothic zone, due to the crushing of the PPM. PMID- 8004648 TI - [Role of glucose in determining arterial hypertension in type 2 diabetes mellitus: ion hypothesis]. PMID- 8004650 TI - [Does the diabetic patient need special diabetic food?]. AB - At present the diet recommended by the Czech Diabetological Society does not fundamentally differ from the diet recommended to the population of the Czech Republic as a whole. The diet must contain high-fibre foods, provide 55% of the energy as carbohydrates, 30% of the energy should be derived from fats and the protein content should be less than 1 g of protein per kg body weight. The cholesterol intake should not exceed 300 mg/day. The system of intensified insulin therapy made a flexible schedule time, of food intake for type I diabetics possible. For diabetics type II the basic provision is a low energy diet which leads to body weight reduction, as the great majority of these patients is overweight. Products described as "dia" or products where on the wrapping it is maintained that they are suitable for diabetics can be divided into two groups, depending on the sweetener used. Products containing non-caloric sweeteners (saccharin, aspartam, acesulfam or so far not permitted cyclamate) have a markedly reduced energy content and are thus suitable in particular for type II diabetics. Products sweetened with fructose, xylitol, sorbitol have as a rule the same or a similar energy values as sucrose containing products and are of no advantage for diabetics type II who are frequently obese. This is why it will be useful to abandon labelling such as "dia-product" or "product suitable for diabetics". This description should not be permitted and the term "low-energy food" should be used. It will be necessary to define precise criteria for these foodstuffs. PMID- 8004651 TI - [Use of yoga in psychiatry]. AB - The author gives an account of his experience with the application of yoga in prevention and treatment of alcohol and drug related problems, in psychosomatic medicine, sexuology, treatment of neuroses, in gerontopsychiatry etc. The problem when using yoga in psychiatry is active cooperation; systemic interactions must be foreseen, it is important to warn against competitiveness and specific indications and contraindications of different yoga exercises must be respected. Yoga is also a suitable element of prevention of professional stress in the health services. PMID- 8004652 TI - [The new international psychiatric classification ICD-10. I. General principles and historical development]. AB - The new international psychiatric classification, ICD-10, involves changes in the theoretical concept of the existing classification system. The change is associated with a shift of the general concept of medical classification which is influenced in particular by new research technologies, the development of programmes of extramural and social care and the penetration of computing technique into medical research. The contemporary psychiatric classification belongs to the agonistic (atheoretical) model which is typical by its pragmatic, clinical approach to diagnosis and classification. Phenomenology and an operational pattern of the classification is emphasized. PMID- 8004653 TI - [Infectious endocarditis and congenital heart defects in adults]. AB - BACKGROUND: Infective endocarditis still remains a cardiological menace. However, the type of predisposing diseases has changed: the incidence of rheumatic heart disease in advanced countries has declined, advances made in the surgical and medicamentous treatment of inborn heart disease are the reasons why we are encountering, with increasing frequency, infective endocarditis which develops on their background. METHODS AND RESULTS: The objective of the investigation was to assess the frequency of infective endocarditis and predisposing diseases. During the time interval between 1987 and 1991 16 patients (50% younger than 50 years) were hospitalized with the diagnosis of infective endocarditis. Rheumatic valvular damage and inborn heart disease were the predisposing factor in 25%. All patients were younger than 30 years (mean 24, range 18-30), and half the patients suffered from defects of the ventricular septum. Other defects were tetralogy of Fallot and inborn aortic stenosis. In 10% of the patients infective endocarditis developed on the background of a mitral valve prolapse with regurgitation. Echocardiographic examination confirmed the diagnosis in almost 70% by revealing vegetation. Bacteriological examination revealed the agent in 60%, most frequently it was Streptococcus viridans. The mortality rate in the group was 13%. CONCLUSIONS: The recorded incidence of infective endocarditis, 1.5 pro mille, is consistent with data in the literature. Corrected and not corrected heart disease plays an important role as predisposing disease. Despite the opportunity of intensive antibiotic treatment, the mortality remains high--13%. PMID- 8004654 TI - [Angiotensin converting enzyme inhibitors in controlled hypotension during spinal surgery]. AB - BACKGROUND: Controlled hypotension is an advantage during spondylosurgical operations: the objective is to achieve a mean arteriae pressure of 8 kPa (60 mm Hg). The most frequently used 0.01% solution of sodium nitroprusside must be increased in some patients to amounts which involve the risk of intoxication. This applies to patients with an increased sympathoadrenal activity and ready mobilization of the renin-angiotensin system. The objective of the present investigation was to test the inhibitor of the angiotensin converting enzyme in hypotension controlled by nitroprusside. METHODS AND RESULTS: To twenty patients before a spondylosurgical operation as premedication angiotensin converting enzyme inhibitor (ACE)--captopril--was administered, 25 mg by the oral route. The control group was formed by 20 patients with spondylosurgery under controlled hypotension with nitroprusside administration. The effect of captopril was manifested by a reduced amount of nitroprusside needed to maintain the median pressure of 8 kPa; in the captopril group 1.073 +/- 0.52 microgram.kg-1.min-1 was used, as compared with 1.786 +/- 1.04 micrograms.min-1 in the control group (p < 0.01). Concurrently monitored values of plasma renin activity were higher in the patients given captopril: 7.352 +/- 5.75 nmol.l-1, as compared with 5.583 +/- 3.73 nmol.l-1 (p < 0.05). CONCLUSIONS: Premedication with ACE inhibitor (captopril), even when administered in small doses via p. o., reduced the sodium nitroprusside consumption by as much as 60%. The elevated plasma renin values were objective evidence of the effect of captopril. PMID- 8004655 TI - [The Point System after 3 years]. PMID- 8004656 TI - [Rapidly progressive glomerulonephritis in a solitary kidney positive for anti glomerular basement membrane antibodies and antineutrophil cytoplasmic antibodies]. AB - The authors describe the case-report of a 72-year-old female patient with acute failure of a solitary kidney with complete functional breakdown which developed within several days and was due to rapidly progressive glomerulonephritis (RPGN) with concurrent positivity of antineutrophil cytoplasmatic autoantibodies (ANCA) and anti-glomerular basement antibodies (AGBMA). Intensive combined immunosuppressive therapy with methyl prednisolone, cyclophosphamide and azathioprine and concurrent plasmaphereses led to negativity of both types of antibodies but were not able to restore sufficient renal function and regular dialysis treatment to be started. Subsequently AGBMA remained negative, while ANCA became again positive. Despite this partial restoration of renal function was manifested by an increased diuresis and the frequency of dialyses could be reduced. The case-report has several remarkable features. An uncommon RPGN of the antirenal type is involved, moreover in a solitary kidney with concurrent C-ANCA positivity. The concurrent presence of ANCA and AGBMA autoantibodies in RPGN has been described in the literature only in several tens of cases. So far it was not described in our country. Based on their experience the authors conclude: 1. a solitary kidney cannot be considered in case of suspected RPGN as a strict contraindicatio of renal biopsy, 2. RPGN with concurrent positivity of ANCA and AGBMA is indicated for long-term immunosuppressive therapy on account of a more favourable prognosis than simple antirenal RPGN, and also with regard to a possible suspected systematic vasculitis.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8004658 TI - [Society of Czech Physicians in Prague. Current cardiology problems in clinical practice. XI. Lectures presented 22 November 1993]. PMID- 8004657 TI - [Ethical or legal problems in Operation Desert Storm?]. PMID- 8004659 TI - Membranes for dialysis. AB - In the submitted review the authors give an account of contemporary problems of membranes for dialysis available at present. Although the authors mention also cellulose based membranes (membranes made from unmodified regenerated cellulose, synthetic modified cellulose membranes produced by chemical transformation of cellobiose), the main attention is paid to polymer membranes--typical synthetic polymers, i.e. polysulphone (PSu), polyacrinon nitrate (PAN), polyamide (PA), ethyl vinyl alcohol polymers (EVAL), polyester mixtures formed by polyacrylonitrile and polyether sulphone (PEPA). The authors describe their adsorption capacity, possibility of sterilization and specific problems of interaction with different drugs. In the conclusion the authors outline demands on the development of modern membranes and their problems in future. PMID- 8004660 TI - [Insulin resistance in essential and nephrogenic hypertension]. AB - Hypertension is an important risk factor of atherosclerosis, glomerulosclerosis and progression of nephropathies and its risk is enhanced by concurrent insulin resistance (IR) which is encountered in essential as well as nephrogenic hypertension almost in half the patients and is an independent risk factor by increasing VLDL and lowering HDL cholesterol. The finding on the impact of a raised concentration of free intracellular Ca and reduced concentration of free intracellular Mg even without changes of the plasma Mg concentration in essential hypertension suggests changes in the compartmentalization of these minerals. In nephrogenic hypertension there are no changes in the intracellular free Mg concentration. These differences, however, do not reduce the importance of these minerals in the pathogenesis of hypertension and IR. They are the baseline for further research. PMID- 8004661 TI - [Erythropoietin secretion in patients with chronic obstructive lung diseases during normobaric oxygen inhalation]. AB - BACKGROUND: Patients with chronic obstructive pulmonary disease (COPD) are characterized by compensatory polycythaemia probably induced by increased erythropoietin (EPO) secretion in the kidneys. METHODS AND RESULTS: As the regulatory mechanisms of erythropoietin secretion in chronic obstructive pulmonary disease are scarcely known we studied plasma EPO levels in 14 patients with COPD (pO2 = 61.9 +/- 1.4 mm Hg, Hct = 47.8 +/- 1.1%) under basal conditions, after two hours of isobaric oxygen breathing and two and four hours after discontinued oxygen breathing. The control group consisted of 12 healthy subjects (pO2 = 87.5 +/- 2.2 mm Hg, Hct = 43.7 +/- 1.6%). Under basal conditions patients with COPD showed significantly higher plasma erythropoietin levels as compared with healthy controls. Oxygen breathing was followed by a significant decline of plasma EPO levels both in patients with COPD as in the control group. This decline was significantly more marked and of longer duration in COPD patients than in healthy controls. CONCLUSIONS: 1. Patients with chronic obstructive pulmonary disease are characterized by significantly higher plasma EPO levels as compared with healthy subjects. 2. The renal oxygen sensor function involved in the regulation of EPO secretion seems to be altered in COPD patients. PMID- 8004662 TI - [Alcohol and health--friend or foe?]. AB - BACKGROUND: The association of alcohol with a number of diseases, accidents, traffic and word injuries, psychoses, degenerative nervous processes and some organ malignities is known and has been proved. An exception is formed by population studies providing evidence of a reduced risk of development of ischaemic heart disease, incl. mortality from the latter. Our population has a high beer consumption: In the West Bohemian region the consumption is 180-200 l of beer per head per year. We were concerned with the problem of the influence of this consumption on the prevalence of IHD, myocardial infarction and some tumours and the general mortality of middle-aged men. METHODS AND RESULTS: The investigation started in 1976 comprised 3758 men aged 40-50 years. On account of manifest disease 171 subjects were eliminated and in the general evaluation after 12 years another 192 subjects could not be included. The final analysis was made in 3395 men, mean age 44.6 +/- 3.6 years, BMI 27.0 +/- 3.2, mean systolic pressure 133.1 +/- 18 mm Hg (17.74 +/- 2.4 kPa), mean diastolic pressure 83.2 +/- 10.7 mm Hg (11.0 +/- 1.5 kPa) and mean serum cholesterol values 5.69 +/- 0.99 mmol/l. A BMI above 29 was recorded in a total of 835 men (23.6%), systolic pressure above 160 mm Hg (21.23 kPa) in 302 men, diastolic pressure higher than 90 mm Hg (11.98 kPa) in 1004 (28.4%); serum cholesterol above 6.7 mmol/l was recorded in 491 (13.9%) of the examined subjects, regular smoking was admitted by 1915 (54.1%) and regular alcohol intake by 1815 (51.3%) of the investigated subjects. The mean follow-up period was 10.73 years. For statistical analysis multiple logistic regression was used and the relative risk expressed as the "odds ratio" (OR) standardized for a number of variables known to influence in a comprehensive way selected final indicators. Approximately 50% of the men were smokers and consumed alcohol. Regular alcohol intake was associated with a significantly lower risk (odds ratio 0.87). The significant difference was, however, not found when the data were standardized for age, blood pressure, family-history and leisure activities. Separate assessment of the relative risk of alcohol for fatal and non-fatal acute myocardial infarction and for the total mortality rate revealed the following risks (expressed as OR and 95% confidence limit in parentheses: OR for fatal infarction = 0.85 (0.44-1.64), not significant), OR for non-fatal infarction = 0.84 (0.60-1.17) and OR for the general mortality = 0.89 (0.68-1.17): both the latter values are at the borderline of statistical significance (p = 0.05-0.1). When smokers drink regularly, they have a significantly lower risk of non-fatal infarctions (but not fatal infarctions!). This effect is not found in non-smokers. The relative risk for the development of tumours in smokers-drinkers is insignificantly elevated, OR = 1.55 (0.89-2.75). The largest number of malignities was lung cancer. Regular smokers who drink alcohol have a treble risk of developing lung cancer, as compared with abstainers: OR = 2.96 (1.07-8.23) a statistically significant increase. CONCLUSIONS: From the investigation it is apparent that regular alcohol intake reduces the rate of all coronaries in middle-aged men, but this protective effect applies only to non-fatal myocardial infarctions, in particular in smokers. No effect on the general mortality was proved. However, there was evidence of a positive association between alcohol intake and lung cancer. Alcohol potentiates (3x) the relative risk of development of lung cancer in smokers. PMID- 8004663 TI - [Changes in amino acids in a regular dialysis program]. AB - BACKGROUND: Dialyzed patients are chronically in a state of negative nitrogen balance, and amino acids, their building stones, are also significantly affected by dialysis. The purpose of the present investigation was to assess whether they should be supplied, how frequently and for how long and how they are influenced by the usual diet of patients. METHODS AND RESULTS: The examination was made in a group of 13 patients included in a regular haemodialysis programme. Their mean age was 53.2 +/- 12.4 years, they were dialyzed for an average period of 55 months, maximum 163 months. The patients were dialyzed three times per week for four hours, bicarbonate dialysate was used. The patients' diet was not modified in any way. A total of 52 haemodialysis were examined: losses of alpha-amino nitrogen were monitored as well as changes of serum concentrations of different amino acids. Their mean losses were 119 +/- 54.69 mmol/4 h: this corresponds to 10.5 +/- 4.8 mg amino acids. The dialysis clearance was on average 122.7 +/- 63.2 ml/min. This value did not differ significantly from the dialysis clearance of urea, but it was significantly higher than creatinine clearance (p < 0.05). During dialysis a significant drop (p < 0.001) of the plasma concentration of amino nitrogen occurred, however, the changes of serum concentrations of amino acids differed. A significant drop was recorded in serum concentrations of histamine, lysine, cysteine, methionine, tyrosine, glycine, asparagine, citrullin, glutamine, taurine. Before the beginning of dialysis the values of valine, lysine, threonine, serine, alanine and asparagine were lower than corresponds to the reference interval in healthy subjects. CONCLUSIONS: Changes of serum concentrations of individual amino acids are significantly influenced not only by their losses into the dialysate but also by their shift from cells into the extracellular fluid and by resorption from the digestive tract during protein intake in the course of dialysis. An adequate supply of high quality protein can compensate for these losses. Investigation of serum concentration of individual amino acids does not record their kinetic changes but can give an idea on the effectiveness of the dietary regime. PMID- 8004664 TI - [Hypofibrinolysis after venous occlusion in patients treated with long-term hemodialysis]. AB - BACKGROUND: Haemodialysis patients with chronic renal failure suffer not only from thromboses of the vascular access but frequently also from atherosclerosis with thrombotic complications. Knowledge of the etiopathogenesis of thrombotic complications in haemodialysis patients are incomplete. The aim of the present study was to evaluate fibrinolysis at the level of plasminogen activation under conditions of a dynamic test, using methods which reflect sensitively and specifically the activity of the tissue-type plasminogen activator (t-PA) and the activity of the inhibitor of the tissue-type plasminogen activator (PAI-1). METHODS AND RESULTS: The group of examined subjects was formed by 16 patients (9 men and 7 women, mean age 42 years, range 26-63) who suffered from chronic renal failure (causes: 9x chronic glomerulonephritis, 6x interstitial nephritis, 1x polycystic kidneys) treated by long-term haemodialysis on average for 52 (20-110) months; the control group of 11 healthy volunteers was very close as regards age distribution. t-PA and PAI-1 were examined after stimulation by venous occlusion (VO). In healthy subjects VO significantly raises the t-PA activity (first value before, second after VO: t-PA 0.81-2.19 IU/ml, p < 0.01), specific t-PA activity (0.19-0.31 IU/ng, p < 0.05) and t-PA/PAI (0.06-0.24 IU/U, p < 0.01, decreases PAI activity (11.80-10.98 U/ml, p < 0.05) and specific PAI activity (0.52-0.40 U/ng, p < 0.01). In the group of haemodialysis patients VO did not change significantly the t-PA activity (p = NS), the specific t-PA activity (p = NS), nor the ratio of t-PA/PAI (p = NS); the PAI declined significantly (13.78-10.65 U/ml, p < 0.05), similarly as the specific PAI activity (0.97-0.65 U/ng, p < 0.01). From comparison of the results of fibrinolysis from healthy and dialysis subjects ensues that the response to VO in dialysis patients differs from that in healthy subjects. CONCLUSIONS: Dialysis patients have impaired fibrinolysis manifested by a lacking rise of activity of the plasminogen tissue activator after stimulation by venous occlusion. The small rise of t-PA activity after venous occlusion can contribute to the development of thrombotic complications in haemodialyzed patients. PMID- 8004665 TI - [Distorting data]. PMID- 8004666 TI - Breakpoint break for consortium studying adult polycystic kidney disease. PMID- 8004667 TI - From the elephant to E. coli: SRP-dependent protein targeting. PMID- 8004668 TI - Epstein-Barr virus strategy in normal and neoplastic B cells. PMID- 8004669 TI - NF-AT-AP-1 and Rel-bZIP: hybrid vigor and binding under the influence. PMID- 8004670 TI - E1A-associated p300 and CREB-associated CBP belong to a conserved family of coactivators. PMID- 8004671 TI - Hydrogen peroxide mediates amyloid beta protein toxicity. AB - Amyloid beta protein (A beta) is a 40-43 amino acid peptide that is associated with plaques in the brains of Alzheimer's patients and is cytotoxic to cultured neurons. Using both primary central nervous system cultures and clonal cell lines, it is shown that a number of anti-oxidants protect cells from A beta toxicity, suggesting that at least one pathway to A beta cytotoxicity results in free radical damage. A beta causes increased levels of H2O2 and lipid peroxides to accumulate in cells. The H2O2-degrading enzyme catalase protects cells from A beta toxicity. Clonal cell lines selected for their resistance to A beta toxicity also become resistant to the cytolytic action of H2O2. In addition, A beta induces the activity of NF-kappa B, a transcription factor thought to be regulated by oxidative stress. Finally, A beta-induced H2O2 production and A beta toxicity are blocked by reagents that inhibit flavin oxidases, suggesting that A beta activates a member of this class of enzymes. These results show that the cytotoxic action of A beta on neurons results from free radical damage to susceptible cells. PMID- 8004672 TI - Cellular commitment to oncogene-induced transformation or apoptosis is dependent on the transcription factor IRF-1. AB - The transcriptional activator interferon regulatory factor 1 (IRF-1) and its antagonistic repressor IRF-2 are regulators of the interferon (IFN) system and of cell growth. Here we report that embryonic fibroblasts (EFs) from mice with a null mutation in the IRF-1 gene (IRF-1-/- mice) can be transformed by expression of an activated c-Ha-ras oncogene. This property is not observed in EFs from wild type or IRF-2-/- mice but is still observed in EFs from mice deficient in both genes. The transformed phenotype of ras-expressing IRF-1-/- EFs could be suppressed by the expression of the IRF-1 cDNA. Thus, IRF-1 functions as a tumor suppressor. Furthermore, expression of the c-Ha-ras oncogene causes wild-type but not IRF-1-/- EFs to undergo apoptosis when combined with a block to cell proliferation or treated by anticancer drugs or ionizing radiation. Hence, IRF-1 may be a critical determinant of oncogene-induced cell transformation or apoptosis. PMID- 8004673 TI - Dihydropyridine receptor mutations cause hypokalemic periodic paralysis. AB - Hypokalemic periodic paralysis (hypoKPP) is an autosomal dominant skeletal muscle disorder manifested by episodic weakness associated with low serum potassium. Genetic linkage analysis has localized the hypoKPP gene to chromosome 1q31-q32 near a dihydropyridine (DHP) receptor gene. This receptor functions as a voltage gated calcium channel and is also critical for excitation-contraction coupling in a voltage-sensitive and calcium-independent manner. We have characterized patient specific DHP receptor mutations in 11 probands of 33 independent hypoKPP kindreds that occur at one of two adjacent nucleotides within the same codon and predict substitution of a highly conserved arginine in the S4 segment of domain 4 with either histidine or glycine. In one kindred, the mutation arose de novo. Taken together, these data establish this DHP receptor as the hypoKPP gene. We are unaware of any other human diseases presently known to result from DHP receptor mutations. PMID- 8004674 TI - Isolation of the gene for McLeod syndrome that encodes a novel membrane transport protein. AB - McLeod syndrome is an X-linked multisystem disorder characterized by abnormalities in the neuromuscular and hematopoietic systems. We have assembled a cosmid contig of 360 kb that encompasses the McLeod gene locus. A 50 kb deletion was detected by screening DNA from patients with radiolabeled whole cosmids, and two transcription units were identified within this deletion. The mRNA expression pattern of one of them, designated as XK, correlates closely to the McLeod phenotype. XK encodes a novel protein with structural characteristics of prokaryotic and eukaryotic membrane transport proteins. Nucleotide sequence analysis of XK from two unrelated McLeod patients has identified point mutations at conserved splice donor and acceptor sites. These findings provide direct evidence that XK is responsible for McLeod syndrome. PMID- 8004675 TI - The polycystic kidney disease 1 gene encodes a 14 kb transcript and lies within a duplicated region on chromosome 16. The European Polycystic Kidney Disease Consortium. AB - Autosomal dominant polycystic kidney disease (ADPKD) is a common genetic disorder that frequently results in renal failure due to progressive cyst development. The major locus, PKD1, maps to 16p13.3. We identified a chromosome translocation associated with ADPKD that disrupts a gene (PBP) encoding a 14 kb transcript in the PKD1 candidate region. Further mutations of the PBP gene were found in PKD1 patients, two deletions (one a de novo event) and a splicing defect, confirming that PBP is the PKD1 gene. This gene is located adjacent to the TSC2 locus in a genomic region that is reiterated more proximally on 16p. The duplicate area encodes three transcripts substantially homologous to the PKD1 transcript. Partial sequence analysis of the PKD1 transcript shows that it encodes a novel protein whose function is at present unknown. PMID- 8004676 TI - COPII: a membrane coat formed by Sec proteins that drive vesicle budding from the endoplasmic reticulum. AB - In vitro synthesis of endoplasmic reticulum-derived transport vesicles has been reconstituted with washed membranes and three soluble proteins (Sar1p, Sec13p complex, and Sec23p complex). Vesicle formation requires GTP but can be driven by nonhydrolyzable analogs such as GMP-PNP. However, GMP-PNP vesicles fail to target and fuse with the Golgi complex whereas GTP vesicles are functional. All the cytosolic proteins required for vesicle formation are retained on GMP-PNP vesicles, while Sar1p dissociates from GTP vesicles. Thin section electron microscopy of purified preparations reveals a uniform population of 60-65 nm vesicles with a 10 nm thick electron dense coat. The subunits of this novel coat complex are molecularly distinct from the constituents of the nonclathrin coatomer involved in intra-Golgi transport. Because the overall cycle of budding driven by these two types of coats appears mechanistically similar, we propose that the coat structures be called COPI and COPII. PMID- 8004677 TI - Drosophila wingless sustains engrailed expression only in adjoining cells: evidence from mosaic embryos. AB - The wingless protein is secreted, but it is not known whether it acts only on cells near to its site of synthesis or whether it has a longer range. Here, we use mosaic Drosophila embryos to estimate the range of wingless as it acts to maintain expression of the engrailed gene. We find that expression of engrailed is often sustained in those wingless- cells that are located near a wildtype patch of tissue, but this is not invariably so. Also, the numbers of cells maintaining engrailed expression are small. From these findings, we argue that wingless-expressing cells sustain engrailed expression only in adjoining cells. The wingless gene is also needed for maintenance of its own expression; using mosaics, we find that the range of this action is short as well. PMID- 8004678 TI - A lineage-specific transcriptional silencer regulates CD4 gene expression during T lymphocyte development. AB - During development of T lymphocytes, differential regulation of expression of the CD4 and CD8 glycoproteins is coupled to the choice of one of two pathways of differentiation. Thymocytes that express both of these coreceptors commit to either the helper lineage, shutting off CD8, or the cytotoxic lineage, shutting off CD4. We have used transgenic mice to identify an intronic regulatory region that controls CD4 gene expression during development. This region selectively extinguishes transgene expression in CD4-CD8+, but not CD4+CD8- nor CD4+CD8+ T cells. It also represses gene expression in CD4-CD8- immature thymocytes, indicating that the CD4 gene is derepressed during differentiation from the CD4 CD8- to the CD4+CD8+ stage. The negative element(s) is both orientation and position independent and acts also on heterologous regulatory sequences. Its properties are functionally similar to those of silencers described in yeast and in Drosophila, suggesting that we have identified a developmentally regulated vertebrate transcriptional silencer. PMID- 8004679 TI - A role for transcription and FRGY2 in masking maternal mRNA within Xenopus oocytes. AB - We find that mRNA synthesized within the Xenopus oocyte nucleus is translated with an efficiency 50 times less than that of mRNA injected into the oocyte cytoplasm. For histone H1 mRNA this effect is independent of mRNA splicing, nuclear export, and the promoter driving transcription. The mRNA synthesized in vivo is translationally competent but is masked from the translational machinery in the cytoplasm through association with proteins including frog Y-box protein 2 (FRGY2). We find that overexpression of FRGY2 facilitates the translational repression of mRNA synthesized within Xenopus oocytes. The requirement for transcription to occur in vivo before a translationally repressed state can be established suggests that these two events are functionally coupled in Xenopus oocytes. PMID- 8004680 TI - Three-dimensional structure of hepatitis B virus core particles determined by electron cryomicroscopy. AB - Human hepatitis B virus core protein expressed in E. coli assembles into two sizes of particle. We have determined their three-dimensional structures by electron cryomicroscopy and image processing. The large and small particles correspond to triangulation number T = 4 and T = 3 dimer clustered packings, containing 240 and 180 protein subunits, respectively. The local packing of subunits is very similar in the two sizes of particle and shows holes or channels through the shell. The native viral core particle packages RNA and is active in reverse transcription to DNA. The holes we observe may provide access for the necessary small molecules. Shells assembled from the intact core protein contain additional material, probably RNA, which appears as an icosahedrally ordered inner shell in the three-dimensional map. PMID- 8004681 TI - ["Revolution psychoses" in 1989 and their catamnesis]. AB - In the submitted paper the author deals in detail with patients hospitalized in two large Moravian sanatoria on account of psychotic disorders in the development of which events of November 1989 played some part. The author sought in these patients common anamnestic data, analyzed the psychopathological picture of the disease and finally subjected all the patients to a three-year catamnestic follow up. The results were compared with several publications dealing with the same subject. The author had, however, the advantage of a longer follow-up and more extensive sources of information, whereby she made also use of contact in writing with former patients. The achieved results were processed by statistical methods, compared also in parts of the group classified by age and sex. In the presented paper only the most interesting data are given. The most positive conclusion is the fact that 31.43% of the group had no longer any psychic complaints, 81.63% of the group work (and another 6.06% returned to work after invalidization). With one exception all patients or their doctors evaluate the present situation at least as satisfactory. PMID- 8004682 TI - [Actualizing tendency and specific motives in human behavior]. AB - In the presented investigation the author analyzes in more detail the relationship between the actualizing tendency and specific motives in the personality theory and therapy elaborated by C. Rogers. She discusses conditions inevitable for effective psychotherapy which were defined arbitrarily, based on observations. She mentions the results of many research projects from this area. PMID- 8004683 TI - [The sibling constellation in neurotic patients]. AB - The authors compared the frequency of the positions among siblings in the neurotic and the control group. The investigation was performed on 582 persons, 435 of them had undergone treatment in the psychotherapeutic department for neuroses. The rest of them, the control group, had never been treated for neurosis. It does not seem that the position of the oldest, the youngest and the only child leads to neurotic disorders. The most risky position is evident by the middle sister. However, validity of these findings is limited by methodological reasons. PMID- 8004684 TI - [50 years since the founding of hospital inpatient psychiatric care in Pilsen]. PMID- 8004685 TI - [Orgasmic expulsions in women]. AB - Orgasm is in some women accompanied by the release of fluid from the external genitalia. This fluid can sometimes eject under pressure and thus resemble male ejaculation. It may presumably originate in the vagina, in the bladder (orgastic urination) or in the paraurethral (Skene's) glands, labeled by some authors as the female prostate. Analysis of the fluid samples showed it to be urine, secretion of Skene's glands or a mixture of both. The relationship of these expulsions to the stimulation of the vaginal G spot has been reported. Zaviacic et al. (1988) established in female volunteers undergoing digital stimulation of the G spot that in some women there is no expulsion, in some there is expulsion accompanied by orgasm and in some expulsions occur easily without orgasm or even without sexual arousal. Our own findings are based on the use of the sexological questionnaire SGZ, which contains items concerning the occurrence of "release of fluid" during orgasm or of "expulsion of fluid, similarly as in male ejaculation". We obtained data from 200 women treated for the neurosis and from 100 female health professionals and counselors. Organistic expulsions resembling male ejaculation were reported in 6% of both samples. Additional 13% had at least some experience with such expulsions. Release of fluid without ejaculation was reported by approximately 60% of females in both samples. We consider "female ejaculation" to be a rare phenomenon, which nevertheless deserves attention in sexological consultations. It should not cause feelings of shame, but should be accepted as a normal part of female sexual reaction. PMID- 8004686 TI - [Theoretical and empirical foundations of transpersonal psychology]. AB - In this lecture, the new insights and strategies that transpersonal psychology offers will be discussed in relation to the global crisis. Western academic psychiatry, psychology, and psychotherapy are ethnocentric; they tend to see their point of view as being superior to the perspectives of all the other cultural groups. They are also pragmacentric in that they take into considerations only experiences and observations made in the ordinary state of consciousness (with the exception of dreams). Such an approach makes no distinction between mysticism and psychosis and pathogizes spiritual and healing practices of ancient and aboriginal cultures. In this lecture, the results of serious study of the entire spectrum of human experience will be discussed, including non-ordinary states of consciousness. Such research logically leads to transpersonal psychology, a system that includes and honors the specific contributions of all cultures throughout ages and sees spirituality as an essential dimension of the human psyche and existence. PMID- 8004687 TI - [Affective symptomatology in patients with nonspecific inflammatory bowel diseases]. AB - The authors analyze the results of research focused affective symptomatology in 297 patients with non-specific inflammatory intestinal diseases--ulcerative colitis and Crohn's disease. The results confirmed that 50% of the patients suffer from intense or very intense neurotic symptoms and 20% from a depressive symptomatology of similar intensity. Item analysis suggests predominance of symptoms of vegetative lability, neurasthenia and cognitive depressive symptoms. The extent of affective symptomatology is only to a small degree sex-dependent. Negative factors include a lower level of education and living in a permanent partnership. PMID- 8004688 TI - [Masturbation in adolescents]. AB - Examination of a group of 602 Czech girls and group of 192 Czech boys aged 16 to 18 years revealed that differences in the occurrence of masturbation are in our population markedly greater than in German or American university students. In the examined groups cca 90% boys and only 6% of the examined girls masturbated. There were also marked differences in the frequency of masturbation. In our population so far the consequences of sexual liberalization after social changes at the end of 1989 are not yet manifest. It can be, however, assumed that in our country liberalization will also lead to a diminution of differences in the occurrence and frequency of masturbation between the two sexes. The authors hold the view that an important part is played also by biological factors, in particular those of a hormonal character. PMID- 8004689 TI - Enrollment of certified nurse practitioners in the Illinois Medicaid program. PMID- 8004690 TI - N-STAT: a voice for the future of nursing. PMID- 8004691 TI - 23Na- and 1H-NMR studies of the action of chlorpromazine and imipramine on nigericin-mediated Na+ transport across phosphatidylcholine vesicular membranes. AB - In order to elucidate the action of chlorpromazine (CPZ) and imipramine (IMP) on nigericin-mediated Na+ transport across phosphatidylcholine vesicular membranes, 23Na nuclear magnetic resonance was applied to the exchange system of Na+ ions present at the same concentration inside and outside unilamellar vesicles. CPZ and IMP added to the vesicles in micromolar concentrations produced an equal increase in the carrier-transport rate. The kinetic analysis, together with 1H NMR observations of the reduction in membrane fluidity produced by the drugs and on the direct interaction between drugs and nigericin, allowed us to conclude that the drug-induced promotion of transport occurred not from the formation step of the Na(+)-nigericin complex nor from its diffusion step, but from its dissociation step. The formation of an adduct between drug and nigericin could be the cause of the drug effect and this proceeded much more efficiently at a membrane-water interface (stability constant Kb; 3 x 10(5) M-1) than in methanol (Kb; 5 x 10(2) M-1). The reason for the difference is also discussed. PMID- 8004692 TI - Synthesis of oxygenated cholesterols as structural mimics of phorbol ester-type tumor promoters. AB - We designed several oxygenated steroids in which functional groups including a hydrophobic group are arranged analogously to those of phorbol ester (12-O tetradecanoylphorbol-13-acetate, TPA), with the aim of finding compounds with TPA like activity, but having a different skeleton and a rigid conformation. The designed steroids, 1 beta,5 alpha-dihydroxy-3 beta-hydroxymethylcholestan-6-one (4), 3 beta,5 alpha-dihydroxycholestan-6-one (5), 3 beta-hydroxymethylcholestan-5 alpha-ol-6-one (6) and 1 beta,3 beta,5 alpha-trihydroxycholestan-6-one (7), were synthesized. A related oxygenated steroid isolated from soft coral, cholestane-1 beta,3 beta-5 alpha,6 beta-tetrol (8), was also synthesized. Among these analogs, compound 7 showed weak TPA-like activities in three biological tests: inhibition to protein kinase C and to cytosolic-nuclear tumor promoter-binding protein (CN TPBP), and induction of differentiation of human promyelocytic leukemia cells (HL 60) to monocyte-like cells. On the other hand, compound 5 was found to be a specific ligand for CN-TPBP, but lacked the other TPA-like activities. PMID- 8004693 TI - Meisenheimer rearrangement of azetopyridoindoles, VI. Synthesis of 12 carbaeudistomin and related compounds. AB - For structure-activity relationship investigation of eudistomins 1, 12 carbaeudistomin 3, its 1,10-trans isomer 4, and 11,12-didehydro-12 carbaeudistomin 5 have been synthesized. The [2,3]-Meisenheimer rearrangement of the corresponding N-oxide of the 2-vinylazetopyridoindole 12a bearing a benzenesulfonyl group as a protective group of the indole nitrogen atom afforded the oxazepino ester 14, which was easily isomerized to 20a. Compounds 3 and 4 were synthesized from 14 and 20a, respectively, according to the following reaction sequences [hydrogenation of the double bond (Pd-C/H2), desulfonylation (Mg in MeOH), hydrolysis (AlBr3-EtSH), and Curtius rearrangement (a mixed anhydride method using NaN3), followed by debenzylation (Pd-C/H2)]. The Curtius reaction of the carboxylic acid 27 using DPPA gave the carbamate 29, which was subjected to debenzylation (AlBr3-EtSH) followed by desulfonylation (LiAlH4) to afford 5. Evaluation of anti-influenza virus activities of the amino compounds 3, 4, and 5 revealed that 12-carbaeudistomin 3 possesses a specific activity against influenza virus B. PMID- 8004694 TI - Fungal metabolites. XIII. Isolation and structural elucidation of new peptaibols, trichodecenins-I and -II, from Trichoderma viride. AB - Three new groups of peptaibols, trichodecenins, trichorovins and trichocellins, have been isolated from conidia of the fungus, Trichoderma viride. The structures of trichodecenins-I and -II were established by positive-ion fast-atom bombardment, collision-induced dissociation mass spectrometry and two-dimensional NMR spectroscopy. Trichodecenins-I and -II have a (Z)-4-decenoyl group, six amino acid residues and a leucinol moiety in the molecules. Trichodecenin-II was synthesized by the solution-phase method. PMID- 8004695 TI - Regioselective cleavage reaction of the aromatic methylenedioxy ring. VI. Synthesis of phenothiazine analogues by using the cleavage reaction with sodium methoxide-thiols in dimethyl sulfoxide and evaluation of their biological activities. AB - The reactions of aromatic methylenedioxy compounds containing electron withdrawing groups with sodium methoxide-thiols in dimethyl sulfoxide gave 3- and 4-hydroxybenzene derivatives in good yield by regioselective attack of the thiolate ions on the methylenedioxy ring. The formation mechanism and the reactivity of thiolate ions in the cleavage reaction of the methylenedioxy ring are discussed. Various biologically active compounds, 32a, 32d, 36b, 38b, 41b and 44-47, were prepared from the 4-hydroxybenzene derivatives and their Ca2+ antagonistic activities were evaluated. Among these compounds, 2-(2 bromophenylthiomethoxy)-10-(2-diethylaminoacetyl)-3- methoxyphenothiazine (46) showed the most potent Ca2+ antagonistic activity. Biological activity could be conveniently evaluated by measurement of the peak height of the vanadyl ion (+4 oxidation ion) signal produced by redox reaction between the phenothiazine derivatives and vanadate ion +5 oxidation ion) with ESR spectroscopy. PMID- 8004697 TI - Studies on active substances in herbs used for hair treatment. I. Effects of herb extracts on hair growth and isolation of an active substance from Polyporus umbellatus F. AB - The effects of methanol extracts of 80 herbs on hair growth were investigated, using normal C3H/He mice from which telogen hair on the back had been removed. Eighteen of the extracts apparently promoted hair regrowth on the mice. As one of active principles in Polyporus umbellatus F., 3,4-dihydroxybenzaldehyde was isolated by column chromatography on Amberlite XAD-2, Sephadex LH-20 and silica gel. PMID- 8004696 TI - Synthesis and evaluation of novel thiazolidine derivatives as thromboxane A2 receptor antagonists. AB - A series of 3-benzoyl or 3-phenylsulfonyl-2-substituted thiazolidine derivatives were synthesized, and evaluated for their thromboxane A2 (TXA2) receptor antagonizing effect on (15S)-15-hydroxy-11 alpha,9 alpha-(epoxymethano)prosta 5(Z),13(E)-dienoic acid (U-46619)-induced aggregation of rabbit platelet-rich plasma (PRP). A simple 2-aryl-thiazolidine derivative, 3-benzoyl-2-(4-hydroxy-3 methoxyphenyl)thiazolidine (5a), showed mild TXA2 receptor antagonist activity. Modification of 5a led to 2-chloro-4-[3-(4-chlorophenylsulfonyl)thiazolidin-2 ylmet hyl]phenoxyacetic acid (29d), which showed 10 times more potent TXA2 receptor antagonist activity than 5a. PMID- 8004698 TI - Studies of human immunodeficiency virus type 1 (HIV-1) protease inhibitors. III. Structure-activity relationship of HIV-1 protease inhibitors containing cyclohexylalanylalanine hydroxyethylene dipeptide isostere. AB - Systematic replacement of the P4-P2 subsites of substrate-based human immunodeficiency virus type 1 protease (HIV-1 PR) inhibitors containing cyclohexylalanylalanine hydroxyethylene dipeptide isostere (Cha-psi [H.E.]-Ala) at positions corresponding to the scissile sites of substrates was carried out. The structure-activity relationship revealed that compounds with the combination of hydrophilic P3 and beta-branched hydrophobic P2 amino acids generally showed strong inhibitory activity against HIV-1 PR. In particular, compounds 4 (Boc-Orn Val-Cha-psi [H.E.]-Ala-NHBun; Bu(n) = n-butyl, Ki = 11 nM) and 6 (Z-Orn-Val-Cha psi [H.E.]-Ala-NHBun, Ki = 8 nM) exhibited good enzyme selectivity, possessing no significant inhibitory activities toward closely related aspartic proteases, pepsin, cathepsin D, and renin. As a possible model system for (anti-Mo-MSV/MLV complex (Mo-MSV = Moloney murine sarcoma virus; MLV = murine leukemia virus)) activity was investigated. Both compounds were found to inhibit moderately the focus formation of Mo-MSV/MLV complex in NIH3T3 cells (compound 4, IC50 = 1.8 microM; compound 6, IC50 = 1.0 microM). PMID- 8004699 TI - Synthesis and platelet-activating factor (PAF)-antagonistic activities of 1,4 disubstituted piperazine derivatives. AB - During the screening of novel platelet-activating factor (PAF) antagonists, we found that 1-(6-methoxy-3,4-dihydro-2-naphthoyl)-4- (3,4,5 trimethoxybenzyl)piperazine and its 4-(3,4,5- trimethoxybenzoyl)piperazine derivatives (1b, 2b) exerted in vitro and in vivo PAF-antagonistic activities. Modifications of the 1-acyl group, the substituent at the 4-position and the piperazine ring of 1a and 2b were examined and from this series 1-(2,3-dimethoxy 6,7-dihydro-5H-benzocyclohepten-8-ylcarbonyl++ +)-4- (3,4,5 trimethoxybenzoyl)piperazine (2g) was found to be one of the most potent PAF antagonists. PMID- 8004700 TI - Synthesis and platelet-activating factor (PAF)-antagonistic activities of trisubstituted piperazine derivatives. AB - 2- or 3-Substituted 1-(2,3-dimethoxy-6,7-dihydro-5H-benzocyclohepten-8- ylcarbonyl)-4-(3,4,5-trimethoxybenzoyl)- and 4-(3,4,5 trimethoxybenzyl)piperazines (2a-s, 3a, b) were prepared and evaluated for antagonistic activities against platelet-activating factor (PAF)-induced platelet aggregation and blood pressure reduction. The 2-methoxymethyl derivative (2f) showed the most potent activities in this series. The enantiomers (R)-(+)-2f and (S)-(-)-2f were synthesized from carbobenzoxy-O-benzyl-L- and D-serine in several steps. In the binding experiment, (S)-(-)-2f showed thirty times greater affinity than the R isomer for the PAF receptor. PMID- 8004701 TI - Studies on anti-platelet agents. II. Synthesis and platelet-inhibitory activity of 5-methyl-4-(3-pyridyl)-2-(substituted benzimidazol-5-yl)imidazoles. AB - A series of 5-methyl-4-(3-pyridyl)-2-(substituted benzimidazol-5-yl)imidazole derivatives was synthesized and tested for anti-platelet and vasodilatory activities. Some compounds were found to have potent activities and low acute toxicity. In particular, 5-methyl-4-(3-pyridyl)-2-(7-chloro-6-methoxy-2- methylbenzimidazol-5-yl)imidazole (26) and 5-methyl-4-(3-pyridyl)-2-(7-chloro-3 methoxy-2-methylbenzimidazol- 5-yl)imidazole (33) exhibited 63% or 51% inhibition at a dose of 10 mg/kg for anti-patelet activity ex vivo in rats, respectively, while they showed no toxicity even at 180 or 100 mg/kg, respectively. Compound 33 also exhibited potent vasodilatory activity (ED50 = 11 micrograms/ml). Enzyme studies on these imidazoles showed that the novel imidazoles inhibit some enzymes which are involved in the platelet aggregation cascade such as cyclooxygenase, phosphodiesterase (PDE), and thromboxane A2 synthetase. The enzyme assay also suggested that the inhibitory activity on PDE may account for the vasodilatory activity of these imidazoles. PMID- 8004702 TI - Synthesis and anti lipid-peroxidation activity of hydroquinone monoalkyl ethers. AB - A series of hydroquinone monoalkyl ethers was synthesized and evaluated for anti lipid-peroxidation activity in rat liver microsomes. 4-Hexyloxy-2,3,6 trimethylphenol (9), having a low redox potential, as well as ascorbic acid exhibited the strongest anti lipid-peroxidation activity (IC50 = 4.2 x 10(-7) M). Structure-activity relationship studies demonstrated that the inhibitory effect of hydroquinone monoalkyl ethers on lipid peroxidation was increased by the acquisition of an optimum hydrophobicity and decreased by an insufficient or excessive hydrophobicity. PMID- 8004703 TI - Synthesis and angiotensin converting enzyme-inhibitory activity of N-[(1S)-1 carboxy-5-(4-piperidyl)pentyl]-L-alanine derivatives. AB - As part of a search for potent and long-lasting angiotensin converting enzyme (ACE) inhibitors, various types of N-[(1S)-1-carboxy-5-(4-piperidyl)pentyl]-L alanine derivatives (7a, 8-11) were prepared. The key synthetic intermediate, N [(1S)-5-(1-benzyloxycarbonyl-4-piperidyl)-1- ethoxycarbonylpentyl]-L-alanine (17a), was synthesized by asymmetric reduction of the alpha-oxoester (13) with Lactobacillus paracasei subsp. paracasei followed by a substitution reaction with tert-butyl L-alaninate (15) and subsequent treatment with hydrogen chloride. Compounds 7a and 8-11 showed potent and long-lasting ACE-inhibitory activity in rats. PMID- 8004704 TI - Syntheses and pharmacological activities of novel optically active inhibitors of acyl-CoA: cholesterol O-acyltransferase: EAB-309 ((R)-N-2-(1,3-benzodioxol-4 yl)heptyl-N'-2,6-diisopropylphenylurea) and its enantiomer. AB - Novel and potent ACAT (acyl-CoA: cholesterol O-acyltransferase) inhibitors, (R)-N 2-(1,3-benzodioxol-4-yl)heptyl-N'-2,6-diisopropylphenylur ea (2a, EAB-309), and its enantiomer 2b (EAB-310), were prepared from 4-(1,3-benzodioxole)carbaldehyde (7) via optically active (R or S)-2-(1,3- benzodioxol-4-yl)heptanoic acid (12a or 12b). Compound 2a showed potent inhibitory effects on ACATs in vitro, and lowered plasma cholesterol in vivo. The IC50 value for inhibition of rat hepatic microsomal ACAT was 5 nM. The ED30 values of hypolipidemic activities in hamster and rat models were 0.25 and 0.75 mg/kg p.o., respectively. The results indicate that 2a has potential to be a novel hypocholesterolemic and antiatherosclerotic agent. The activities of 2a in vitro and in vivo were only several times more potent than those of the enantiomer 2b. Modeling studies suggested that the three dimensional structures of the two enantiomers are similar to each other. PMID- 8004705 TI - Degradation of deltorphins and their analogs by rat brain synaptosomal peptidases. AB - To obtain metabolically stable peptide ligands with high affinity and selectivity for the delta-opioid receptor, the enzymatic stability of deltorphins and their analogs was examined by using a crude rat brain synaptosomal membrane fraction. It was found that deltorphin (DLT: Tyr-D-Met-Phe-His-Leu-Met-Asp-NH2) was easily degraded, producing DLT (1-4) and DLT (1-5) as the major degradation products, whereas [D-Ala2]deltorphin II (DL-II: Tyr-D-Ala-Phe-Glu-Val-Val-Gly-NH2) was very stable. Experiments with some enzyme inhibitors strongly suggested that the degradation of DLT was initiated by cleavage of the Leu5-Met6 bond by a metalloendopeptidase. On the other hand, stability experiments on DL-II analogs demonstrated that the presence of amino acids branched at the beta-carbon atom or with a bulky side chain as residue 5 is of importance for the enzymatic stability. Based on these lines of evidence, some enzyme-resistant DLT analogs were synthesized. PMID- 8004707 TI - Development and application of an enzyme immunoassay for karasurin A, an effective protein component of Trichosanthes kirilowii Max. var. japonicum Kitam. AB - A method was developed for specific estimation of the content of a non-enzymatic protein, karasurin A, in fractions taken during the extraction and purification processes from a natural source. Anti-karokon serum was elicited in rabbits immunized with fragments of karokon, a dried root tuber of Trichosanthes kirilowii Max. var. japonicum Kitam. Rabbit antibody specific for karasurin A was identified in anti-karokon serum by the Western blotting method. After separation by SDS-PAGE, protein bands of purified karasurin A and extracted proteins from a medicinal herb which is a karasurin A source were reacted with anti-karokon serum followed by treatment with horseradish peroxidase (HRP)-labeled Fab' of goat anti rabbit IgG, and then bound HRP-labeled second antibody on protein bands was developed to brown by reaction with a substrate solution of the used enzyme. A novel selected antibody enzyme immunoassay (SAEIA) for karasurin A was developed using selective binding of anti-karasurin A antibody in anti-karokon serum to solid phase karasurin A and HRP-labeled Fab' of the second antibody as the tracer. Specific estimation of the content of karasurin A in several fractions taken during the isolation and purification processes of the protein were possible using the SAEIA method. PMID- 8004706 TI - Synthesis and hypnotic and anti-human immunodeficiency virus-1 activities of N3 substituted 2'-deoxy-2'-fluorouridines. AB - Reaction of 9-[3,5-di-O-(tetrahydropyran-2-yl)-beta-D-arabinofuranosyl]uracil (2) with diethylaminosulfur trifluoride in the presence of pyridine afforded 2'-deoxy 2'-fluororiboside 3a, from which 2'-deoxy-2'-fluorocytidine (4b) has been synthesized in good yield. Compound 3a was deprotected and subsequently treated with various benzyl halides or 2-chloro-4-fluoroacetophenone to give corresponding N3-substituted 2'-deoxy-2'-fluorouridines 5a-c and 6. Compounds 5a c, as well as 6, showed weak hypnotic activity in mice. Compound 4b showed moderate antiviral activity against human immunodeficiency virus-1 but 3b, 5a-c, and 6 were virtually inactive. PMID- 8004708 TI - Structural and conformational studies of [Ile7] and [Leu7]surfactins from Bacillus subtilis natto. AB - A novel [Ile7]surfactin (1), which showed anti-human immunodeficiency virus activity, has been isolated from Bacillus subtilis natto. Structural and conformational analysis of the peptide backbone of [Ile7]surfactin was conducted by a combination of various two-dimensional (2D) nuclear magnetic resonance (NMR), circular dichroism (CD) spectroscopy and simulated annealing calculations, compared with a known [Leu7]surfactin (2). Both surfactins were shown to exist in different conformational states in both polar and apolar solvents. PMID- 8004710 TI - Studies on the constituents of Solidago virga-aurea L. III. Structures of solidagosaponins XXI-XXIX. AB - From the most polar fractions of Solidago virga-aurea L. (Compositae), 9 oleanane type triterpene saponins named solidagosaponins XXI-XXIX (1-9) were isolated, together with a known saponin, virgaureasaponin 2 (10). These saponins are bisdesmosidic glycosides having two monosaccharides at C-3 and four or five monosaccharides at C-28. Their structures were established on the basis of spectroscopic and chemical evidence. PMID- 8004709 TI - Studies on differentiation inducers. IV. Pregnane derivatives from condurango cortex. AB - In connection with the study of differentiation inducers from plants, the methanol extract of Condurango Cortex (bark of Marsdenia condurango REICH, Asclepiadaceae) was investigated to examine its differentiation-inducing activity towards mouse myeloid leukemia (M1) cell line. Six pregnane glycosides, including three new compounds, were isolated as differentiation inducers. Each of the six active glycosides has three or four deoxylated sugars which are well-known to occur in Asclepiadaceae plants. M1 cells were differentiated into phagocytic cells by these glycosides, and they were found to be more effective than their aglycones. Condurangoglycosides A (7) and C (8), having a cinnamoyl group in their aglycones, were the most potent differentiation inducers and M1 cells became phagocytic cells after 24 h treatment with these compounds. PMID- 8004712 TI - Characterization of a novel glucan, which exhibits reticuloendothelial system potentiating and anti-complementary activities, from the rhizome of Cnidium officinale. AB - A novel glucan, called cnidirhan SI, was isolated from the rhizome of Cnidium officinale Makino. It was homogeneous on electrophoresis and gel chromatography, and its molecular mass was estimated to be 1.3 x 10(4). It is composed of D glucose alone, in addition to small numbers of O-acetyl groups. Methylation analysis, nuclear magnetic resonance and enzymic degradation studies indicated it has a high-branched glucan type structure composed of alpha-1,4-linked D glucopyranose residues with both 3,4- and 4,6-branching points. The glucan showed significant reticuloendothelial system-potentiating activity in a carbon clearance test, as well as pronounced anti-complementary activity. This substance is the first example of a branched alpha-glucan with phagocytosis-stimulating and anti-complementary activities. PMID- 8004711 TI - Characterization of two polysaccharides having activity on the reticuloendothelial system from the root of Rehmannia glutinosa. AB - Two acidic polysaccharides, called rehmannan SA and rehmannan SB, were isolated from the dried root of Rehmannia glutinosa Liboschitz. They were homogeneous on electrophoresis and gel chromatography, and their molecular masses were estimated to be 6.4 x 10(4) and 7.9 x 10(4), respectively. They were commonly composed of L arabinose:D-galactose:L-rhamnose:D-galacturonic acid in the molar ratios of 10:10:1:1 (rehmannan SA) and 14:7:3:8 (rehmannan SB), in addition to small amounts of peptide moieties. About eighty percent (rehmannan SA) and about thirty percent (rehmannan SB) of the hexuronic acid residues exist as methyl esters. Reduction of carboxyl groups, methylation analysis, nuclear magnetic resonance and the controlled Smith degradation studies indicated the structural features of rehmannan SB, the major one in terms of the yield. It has a core structural unit of a characteristic rhamnose-rich arabino-3,6-galactan type. Both polysaccharides showed remarkable reticulo-endothelial system-potentiating activity in a carbon clearance test. PMID- 8004714 TI - Senegoses J-O, oligosaccharide multi-esters from the roots of Polygala senega L. AB - From the roots of Polygala senega L. six new oligosaccharides, called senegoses J O, were isolated and their structures were elucidated by spectroscopic and chemical means. These oligosaccharides were esterified with acetic, benzoic, p coumaric and ferulic acids. PMID- 8004713 TI - Saponins from Vietnamese ginseng, Panax vietnamensis Ha et Grushv. collected in central Vietnam. III. AB - Five new dammarane saponins derived from four new aglycones were isolated from the rhizomes and roots of Panax vietnamensis Ha et Grushv. On the basis of physicochemical and spectral evidence, the structures of these compounds were established as 6-O-beta-D-glucopyranosyl 20(S),25-epoxydammarane-3 beta,6 alpha,12 beta,24 alpha-tetrol (1), 6-O-beta-D-xylopyranosyl-(1-->2)-beta-D glucopyranosyl 20(S),25-epoxydammarane-3 beta,6 alpha,12 beta,24 alpha-tetrol (2), 6-O-beta-D-glucopyranosyl dammarane-3 beta,6 alpha,12 beta,20(S),24 xi,25 hexol (5), 3-O-[beta-D-glucopyranosyl-(1-->2)-beta-D-glucopyranosyl]-20-O-beta-D- glucopyranosyl dammarane-3 beta,12 beta,20(S),24 xi,25-pentol (8) and 6-O-beta-D xylopyranosyl-(1-->2)-beta-D-glucopyranosyl 20(S),24(S)-epoxydammarane-3 beta,6 alpha,12 beta,25 xi,26-pentol (10). The trivial names, vina-ginsenoside-R10, R11, -R12, -R13 and -R14, respectively, were assigned to the new saponins. PMID- 8004715 TI - Application of an oily gel formed by hydrogenated soybean phospholipids as a percutaneous absorption-type ointment base. AB - We investigated the possibility of developing an oily gel formed by hydrogenated soybean phospholipids (HSL) as a percutaneous absorption-type ointment base. Liquid paraffin (LP) was used as the oil, and indomethacin (IM), ketoprofen (KP), flurbiprofen (FP) and ibuprofen (IP) were used as model drugs. IM did not dissolve in LP, but solubilized when heated with HSL at a concentration of about 1% with 15% HSL at 95 degrees C. IM gel was thus prepared as follows: IM and HSL were mixed, added into LP, capped tightly, heated in a water bath and cooled. The consistency of the gel increased with increasing IM concentration, indicating some kind of interaction between IM and HSL. The release of IM from the IM gel was faster than that from a preparation in which IM was mixed in gel at room temperature (Gel + IM). The release rate of IM from IM gel was proportional to IM concentrations up to 1%, but became constant above that. Permeation of IM through hairless rat abdominal skin from IM gel was higher than that from the Gel + IM. The permeation rate was proportional to IM concentrations in the range of 0.1 to 0.5% in 15% HSL gel. KP and FP also solubilized in gel when subjected to the same procedure as IM, and their release and permeation increased when they were formulated as gels. However, no evident improvement of permeation was observed in the case of IP, which had high LP solubility. It was suggested that HSL showed no enhancing effect, but solubilized IM, KP or FP, leading to high permeation from the gel. After 3 months' storage, the permeation rate did not change for 0.5% IM in 15% HSL gel, but decreased for 1% IM in 15% HSL gel. This indicates that in the case of 1% IM in 15% HSL gel, IM is in a supersaturated state immediately after preparation and then recrystallizes with time. PMID- 8004716 TI - Recognition of a nucleic acid base by tryptophan-containing peptides: spectroscopic comparison of the interaction of Trp-Gly-Gly-Glu and Trp-Gly-Gly Gln with 7-methylguanine base. AB - As a part of a study to elucidate the functional difference between Glu and Gln side-chains in terms of the recognition of guanine base by tryptophan-containing peptides via cooperative stacking and hydrogen-bond pairing interactions, the binding of 7-methylguanine to Trp-Gly-Gly-Glu and Trp-Gly-Gly-Gln was examined by fluorescence and 1H-NMR methods. Comparison of fluorescence experiments showed a binding preference for Trp-Gly-Gly-Glu over Trp-Gly-Gly-Gln. The analyses of the downfield and upfield shifts of the C2 amino and N7 methyl protons of 7 methylguanine base showed there was hydrogen-bond pairing of Glu and Gln side chains with the base and a stacking interaction of the Trp residue with the base, respectively. However, the hydrogen-bond pairing was more effective in the case of the Glu residue than the Gln residue, indicating the preference of the carboxyl group over the carbamoyl group to form hydrogen-bond pairing with the guanine base. PMID- 8004718 TI - Isolation and characterization of immunosuppressive components of three mushrooms, Pisolithus tinctorius, Microporus flabelliformis and Lenzites betulina. AB - Two components having an immunosuppressive activity were isolated together with non-active pisolactone from Pisolithus tinctorius, and they were deduced to the 24-methyllanosta-8,24(28)-diene-3 beta,22 zeta-diol and a mixture of two new compounds, (22S,24R)-24-methyllanosta-8-en-22,28-epoxy-3 beta,28 alpha-diol and (22S,24S)-24-methyllanosta-8-en-22,28-epoxy-3 beta,28 beta-diol, respectively. Among them, pisolactone and 24-methyllanosta-8,24(28)-diene-3 beta,22 zeta-diol have previously been isolated from the same mushroom. Ergosterol peroxide and 9(11)-dehydroergosterol peroxide were also isolated as active components from this mushroom in small amounts, and from Microporus flabelliformis and Lenzites betulina. The IC50 values of these components were evaluated against proliferation of mouse spleen lymphocytes stimulated with concanavalin A and lipopolysaccharide. PMID- 8004717 TI - Stereochemistry of hydrogen addition to C-25 of desmosterol by sterol-delta 24 reductase of rat liver homogenate. AB - Chemically synthesized (26)- and (27)-methyl-13C-labeled desmosterol (3, 5) were separately incubated with rat liver homogenate. 13C-NMR analysis of the incubation products indicated that the C-25 hydrogen of cholesterol was introduced from the si-face of 3 and the re-face of 5. PMID- 8004719 TI - 1,4,5-trialkyl imidazole system anti-inflammatory properties of new substituted derivatives. AB - In an investigation of the anti-inflammatory properties of five-membered ring nitrogen-containing heterocyclic compounds, two series of derivatives of imidazole were prepared by altering the sites of substitution and by joining aliphatic chains to the nitrogen atom in the 1 position of the imidazole ring. Some of them were more potent inhibitors of carrageenan-induced edema than indomethacin. An electron spin resonance study indicated that these compounds possess anti-radical activity. PMID- 8004720 TI - Platinum and palladium complexes containing ethylenediamine derivatives as carrier ligands and their antitumor activity. AB - We prepared new antitumor active platinum complexes containing N,N'-bis(2 chloroethyl)ethylenediamine (ClEn) as an alkylating carrier ligand in order to obtain increased antitumor effects. Some of the platinum complexes synthesized showed enhanced antitumor activity. However, palladium(II) complexes containing ClEn were inactive against L1210 and P388. PMID- 8004721 TI - New steroidal saponins from the bulbs of Allium giganteum exhibiting potent inhibition of cAMP phosphodiesterase activity. AB - A new spirostanol saponin and two new furostanol saponins were isolated from the fresh bulbs of Allium giganteum together with several known saponins. The structures of the new compounds were determined on the basis of spectroscopic data, the products formed on hydrolysis and by comparing their properties with those of known compounds. The isolated saponins and their derivatives were evaluated for inhibitory activity by examining their action on cAMP phosphodiesterase as a primary screening test to identify new medicinal agents. PMID- 8004722 TI - Synthesis and antiulcer activities of novel 2-[(6,7,8,9-tetrahydro-5H cyclohepta[b]pyridin-9-yl)sulfinyl]-1H- benzimidazole analogues. AB - A synthetic study on a series of benzimidazole derivatives including cycloalka[b]pyridine moiety has been carried out. Among these compounds synthesized, a novel antipeptic agent with 6,7,8,9-tetrahydro-5H cyclohepta[b]pyridine moiety (TY-11345) was found to be superior to omeprazole in (H+ + K+)-ATPase inhibitory activity and antisecretory potencies. PMID- 8004723 TI - Racemization-free synthesis of C-terminal cysteine-peptide using 2-chlorotrityl resin. AB - We investigated the effects of bases, resins, and S-protecting groups on the extent of racemization at the C-terminal cysteine during Fmoc-based(Fmoc=fluoren 9-yl-methoxy-carbonyl) solid phase peptide synthesis. The use of 2-chlorotrityl resin was most effective in suppressing the racemization caused by the base treatment for Fmoc-cleavage. Somatostatin was successfully synthesized with practically no racemization using 2-chlorotrityl resin by Fmoc-chemistry. PMID- 8004724 TI - Bryonolic acid production in hairy roots of Trichosanthes kirilowii Max. var Japonica Kitam. Transformed with Agrobacterium rhizogenes and its cytotoxic activity. AB - The hairy roots of Trichosanthes kirilowii Max, var. japonica Kitam. were induced by Agrobacterium rhizogenes (TCC 15834) on sterile shoots. The axenic culture of hairy roots proliferated 30 to 60-fold based on the initial fresh weight after three weeks of culture in Murashige & Skoog liquid media. Bryonolic acid as the main triterpenoid was isolated in a high yield, together with chondrillasterol from the hairy roots of this plant. Bryonolic acid showed strong inhibition of the growth of B-16 melanoma cells. PMID- 8004725 TI - Variation of lymphocytes in peripheral blood and bone marrow in collagen-induced arthritis. AB - Collagen-induced arthritis (CIA) was found to be useful as an animal model to investigate the mechanism by which rheumatoid arthritis is developed. We therefore studied variations of T and B lymphocytes in peripheral blood and bone marrow in order to ascertain the importance of T and B lymphocytes in the development of CIA. T lymphocyte, which is considered to be associated with the onset and deterioration of CIA, was not changed during the course of CIA, whereas B lymphocyte, which produces anti-type II collagen antibody regarded as an indispensable factor in CIA induction, was significantly decreased in peripheral blood and bone marrow at 10 days after the 2nd immunization when arthritis was able to be detected. In bone marrow, although two cell populations of Ly5/B220 positive cells were detected, only the cell population with lower fluorescence intensity was decreased transiently. These results suggest that B lymphocyte in both bone marrow and peripheral blood is intimately involved in the course of CIA. PMID- 8004726 TI - Camelliasaponins B1, B2, C1 and C2, new type inhibitors of ethanol absorption in rats from the seeds of Camellia japonica L. AB - New type inhibitors of ethanol absorption, camelliasaponins B1, B2, C1 and C2, were isolated from the seeds of Camellia japonica L. The structures of camelliasaponins were elucidated on the basis of chemical and physicochemical evidence. The inhibitory effect of camelliasaponins and related saponins on ethanol absorption have been examined, and it was found that the triterpene oligoglycoside structure having an acyl group was essential to exerting the activity. PMID- 8004727 TI - Enzymatic regioselective acylation of 3-O-beta-D-galactopyranosyl-sn-glycerol by Achromobacter sp. lipase. PMID- 8004728 TI - Structures of novel bufadienolides in the eggs of a toad, Bufo marinus. AB - In this paper, we report chemical structures of five compounds including four novel polyhydroxylated cardiac steroids in the eggs of a toad, Bufo marinus. These cardiac steroids were purified by high-performance liquid chromatography, and their structures were determined to be 11 alpha,19-dihydroxy-telocinobufagin (I), 11 alpha-hydroxytelocinobufagin (II), 11 alpha,19-dihydroxymarinobufagin (III), 11 alpha-hydroxymarinobufagin (IV) and 19-hydroxytelocinobufagin (V) on the basis of spectral data of nuclear magnetic resonance and mass spectroscopy. All the five compounds showed biological activity, as tested by inhibition of Na+,K(+)-ATPase activity and of [3H]ouabain binding to the receptor on Na+,K(+) ATPase. This is the first finding of bufadienolides as cardiac steroids in animal eggs. PMID- 8004729 TI - Who benefits when parents are present during anaesthesia induction in their children? PMID- 8004731 TI - Awake intubation increases intracranial pressure without affecting cerebral blood flow velocity in infants. AB - Tracheal intubation is frequently required in neonatal anaesthetic practice. Awake intubation is one method of securing the airway and in certain circumstances, for many anaesthetists, can be preferable to intubation following induction of anaesthesia. Previous studies have inferred that the elevation in anterior fontanelle pressure observed during tracheal intubation in neonates was caused by an increase in cerebral blood flow although it was never measured. In this study, direct methods were used to observe changes in the cerebral circulation. Thirteen neonates, ASA I to III (E), aged from 1 to 34 days of age were studied. Patients were randomized to receive either tracheal intubation awake or following induction of anaesthesia with thiopentone 5 mg.kg-1 and succinylcholine 2 mg.kg-1. Heart rate, systolic arterial blood pressure, anterior fontanelle pressure, cerebral blood flow velocity (using transcranial Doppler sonography) and oxygen saturation were recorded at the following intervals: baseline (not crying), after intravenous atropine 0.02 mg.kg-1, during laryngoscopy, immediately after insertion of the endotracheal tube, one and five minutes later. The use of atropine masked the cardiovascular responses to intubation. Whereas the change in anterior fontanelle pressure from baseline was different between the groups (P < 0.05), the cerebral blood flow velocity variables were not. The rise in anterior fontanelle pressure seen in the awake group may be attributed to a reduction of the venous outflow from the cranium thereby increasing cerebral blood volume and subsequently the intracranial pressure. PMID- 8004730 TI - Parental upset associated with participation in induction of anaesthesia in children. AB - To evaluate the magnitude of parental upset associated with (1) the features of induction most upsetting to parents; (2) the characteristics of parents most likely to become upset; and (3) the accuracy of the anaesthetist's perception of the magnitude of parental upset. The parents (101 mothers and 43 fathers) of 103 children scheduled for elective outpatient surgery requiring general anaesthesia with induction by mask were asked on admission to participate in this study. Parents and children were educated about anaesthesia and surgery according to unit protocols. Immediately after induction of anaesthesia, the parents were asked to complete a demographic information sheet and the Parental Reactions to Anesthesia Induction Questionnaire. Responses were analyzed using descriptive statistics and content analysis. The most upsetting factors for both mothers and fathers in order of significance were: (1) separation from the child after induction of anaesthesia; (2) watching/feeling the child go limp during induction; and (3) seeing the child upset before induction. Characteristics of parents most likely to become upset revealed positive correlations between the amount of upset between mothers and fathers, mothers of an only child, and mothers or fathers who were health care workers (P < 0.05). The anaesthetist's perception of upset correlated with maternal (P < 0.05), but not parental, self assessment of upset. We conclude that selected factors of parental participation are upsetting for the parents and that recognizing the factors associated with parental upset may enable operating room personnel to minimize these negative consequences. PMID- 8004732 TI - Arterial oxygen desaturation during peripheral venous cannulation in children. AB - Arterial oxygen saturation (SpO2) was measured to determine oxygen desaturation during peripheral venous cannulation prior to induction of anaesthesia in 40 consecutive patients in each of the three age groups; Group I: 1-4 mo, Group II: 4-12 mo, Group III: 12-24 mo. Following premedication with oral trimeprazine tartarate 3 mg.kg-1, one to two hours before operation, baseline SpO2 was noted with child breathing room air. Continuous monitoring during peripheral venous cannulation was done and maximum decrease and duration of SpO2 < 90% was noted. Decreases in mean SpO2, 3.2 +/- 1.4 in Group I, 2.6 +/- 2.0 in Group II and 1.7 +/- 1.9 in Group III, were observed (P < 0.001). Desaturation > or = 4% was noted in 17 patients in Group I, ten patients in Group II and six patients in Group III. Two children, one each in Groups I and II, experienced SpO2 < 90% for 30 sec and 80 sec respectively. We conclude that clinically undiagnosed desaturation occurs during peripheral venous cannulation in healthy children. The authors suggest that continuous monitoring of SpO2 using pulse oximetry should be performed routinely during peripheral venous cannulation. PMID- 8004733 TI - Reduction of postoperative nausea and vomiting with granisetron. AB - The antiemetic effects of granisetron, a selective 5-hydroxy-tryptamine type 3 receptor antagonist, on postoperative nausea and vomiting were studied and compared with placebo and metoclopramide in 60 patients undergoing general anaesthesia for major gynaecological surgery. The patients received a single i.v. dose of either granisetron (3 mg, n = 20) metoclopramide (10 mg, n = 20), or placebo (saline, n = 20) immediately after recovery from anaesthesia. The effects were assessed during the first three and the next 21 hr after recovery from anaesthesia by means of a nausea and vomiting score; 0 = no emetic symptoms, 1 = nausea, 2 = vomiting. The mean scores during 0-3 hr were 0.8, 0.1 and 0.1 after administration of placebo, metoclopramide and granisetron, respectively; the corresponding scores during 3-24 hr were 0.6, 0.5 and 0.1. The scores of the metoclopramide and the granisetron groups were different from the placebo group in the first three hours (P < 0.05). Although there were no differences in the scores during 0-3 hr between the metoclopramide and the granisetron groups, there were differences during 3-24 hr (P < 0.05). It is concluded that granisetron is superior to metoclopramide in the long-term prevention of postoperative nausea and vomiting after anaesthesia. PMID- 8004735 TI - Simple narcotic kits for controlled-substance dispensing and accountability. AB - Operating rooms require a storage, dispensing and accounting system for restricted drugs which satisfies narcotics control authorities and is compatible with efficient care of patients. We describe narcotic kits containing fentanyl morphine-midazolam, alfentanil-midazolam and sufentanil-midazolam, for general operating rooms, and two kits with larger quantities of fentanyl and sufentanil for cardiac operating rooms. The container for each kit is a video cassette holder which has a foam-rubber liner with sculpted depressions for each ampoule. Sealed kits are delivered each morning from pharmacy to the locked narcotics cupboard in the recovery room. On request, the recovery room nurse unlocks the cupboard and the anaesthetist signs out the required kit(s) for the day. A drug utilization form is enclosed with each kit, on which the anaesthetist records the amount of drug administered to each patient, and before returning the kit to the locked narcotics cupboard, the total amount of each drug used, discarded, and returned. Used kits are collected the following morning by a pharmacy technician who reconciles the contents and drug form of each kit. More than 40 staff anaesthetists and a similar number of residents have used the system for seven years, during which time 130,000 patients have passed through the operating rooms. Detection of one case of drug diversion by a staff anaesthetist was made partly by the control system, but mainly by behavioural changes. The system is simple, inexpensive, and effective and has been well received by the departments of pharmacy, anaesthesia, and nursing. PMID- 8004734 TI - Isoflurane compared with nitrous oxide anaesthesia for intraoperative monitoring of somatosensory-evoked potentials. AB - Intraoperative monitoring of somatosensory-evoked potentials is a routine procedure. To determine the depressant effect of nitrous oxide relative to isoflurane, the authors recorded the scalp, cervical and brachial plexus-evoked responses to stimulation of the median nerve under different anaesthetic conditions. Eight subjects, age 35 +/- 6 (SD) yr, weight 68 +/- 12 kg, were studied. Following recording of awake control responses, anaesthesia was induced with thiopentone 5 mg.kg-1 and fentanyl 3 micrograms.kg-1 and was followed by succinylcholine 1 mg.kg-1. During normocapnia and normothermia, and with a maintenance infusion of fentanyl 3 micrograms.kg-1.hr-1, evoked potential recording was repeated under three different anaesthetic conditions; 0.6 MAC nitrous oxide, 0.6 MAC nitrous oxide +/- 0.6 MAC isoflurane, and 0.6 MAC isoflurane. Among the anesthetic conditions, the combination of nitrous oxide isoflurane had the most depressant effect on the cortical amplitude (67 +/- 4% reduction, P < 0.05). Nitrous oxide decreased the cortical amplitude more than an equipotent dose of isoflurane (60 +/- 4% vs 48 +/- 7%, P < 0.05). The latency was unchanged by nitrous oxide, but increased slightly by isoflurane and isoflurane nitrous oxide anaesthesia (1.0 and 0.9 msec respectively, P < 0.05). We conclude that somatosensory-evoked potential monitoring is feasible both during nitrous oxide anaesthesia and isoflurane anaesthesia, but the cortical amplitude is better preserved during 0.6 MAC of isoflurane alone relative to 0.6 MAC of nitrous oxide alone. The depressant effect is maximal during nitrous oxide isoflurane anaesthesia but less than the predicted additive effect. PMID- 8004736 TI - Postoperative respiratory depression following excision of carotid body tumours. AB - This report is of two adult patients who were scheduled for excision of carotid body tumours. One of the patients had bilateral tumours, while the second had a unilateral tumour. In the first, anaesthesia was maintained by nitrous oxide:oxygen and halothane 1-2%. Postoperatively, the intramuscular injection of meperidine 75 mg resulted in apnoea, cyanosis, and loss of consciousness. In the second, anaesthesia was maintained by nitrous oxide:oxygen, supplemented by fentanyl 2 micrograms.kg-1 and incremental doses of vecuronium. Following complete reversal of neuromuscular block, the patient became wide awake but spontaneous breathing was resumed at a rate of only two to three breaths per minute, and the oxygen saturation as monitored by pulse oximetry decreased to 50%. Naloxone 0.4 mg iv increased the respiratory rate to 14 per minute and the oxygen saturation to 98%. The report suggests that surgical excision of carotid body tumours, whether unilateral or bilateral, can be followed by severe postoperative respiratory depression. The complication may be attributed to opioid administration in the absence of peripheral chemoreceptor drive. PMID- 8004737 TI - Transoesophageal echocardiography detects residual ductal flow during video assisted thoracoscopic patent ductus arteriosus interruption. AB - This report describes transoesophageal echocardiographic (TEE) monitoring in a one-year-old boy undergoing patent ductus arteriosus (PDA) interruption. After application of a first vascular clip, echocardiographic monitoring detected incomplete interruption of ductal flow, prompting the surgeon to add a second clip to the ductus. The procedure was performed via a new surgical technique: video-assisted thoracoscopic surgery (VATS). This innovative approach offers many advantages to patient care including reduced postoperative pain and better preservation of pulmonary function. We conclude that the use of TEE monitoring during PDA interruption via the VATS procedure may improve the surgical result, and eliminate reintervention and the complications associated with residual ductal flow. PMID- 8004738 TI - Respiratory acidosis and subcutaneous emphysema during laparoscopic cholecystectomy. AB - A case is presented of a healthy 69-year-old woman who underwent elective laparoscopic cholecystectomy under general anaesthesia. As surgery proceeded she developed hypercapnia (arterial blood PaCO2 = 100 mmHg) and a related respiratory acidosis (arterial blood pH 7.07). The cause was attributed to subcutaneous insufflation and absorption of CO2, directly related to the surgical pneumoperitoneum. PMID- 8004739 TI - Unexpected neurological deficits following recovery from anaesthesia. AB - Two cases of neurological dysfunction are presented. Neurological deficits after recovery from anaesthesia are unusual in young women perioperatively. In the first case, a 39-yr-old woman presented at 36-wk gestation with antepartum haemorrhage and in labour. Pregnancy had been complicated by pre-eclampsia and she underwent emergency Caesarean section under general anaesthesia without complication. The trachea was extubated when she was awake but almost immediately she became hypertensive, obtunded and reintubation was required. Her pupils became fixed and dilated but the Computerised Axial Tomogram (CT) was normal. A coagulopathy was evident. She made a full neurological recovery within 24 hr. On the same day, a previously healthy 41-yr-old woman who had undergone uneventful surgery for uterine prolapse 24 hr previously developed headache, nausea and over the next four hours signs of progressive brainstem ischaemia. The CT scan showed oedema of the mid- and hindbrain. Brainstem death was confirmed 12 hr later and the post-mortem revealed acute dissection of the vertebral artery secondary to cystic medial necrosis. Such dramatic neurological sequelae are rare but the importance of identifying "at risk" groups is underlined as is early recognition of neurological injury postoperatively. PMID- 8004740 TI - Cerebral arteriovenous malformations in children. AB - The treatment of cerebral arteriovenous malformations (AVM) or vascular anomalies are challenging neurosurgical procedures for an anaesthetist. Large AVMs are uncommon in children. Only 18% of AVMs become symptomatic before the age of 15 yr. This series reviews the experience at this institution during the period of 1982 to 1992. The symptoms at the time of presentation are varied and include haemorrhage (50%), seizures and hydrocephalus (36%) or congestive cardiac failure (18%). Symptoms of congestive heart failure predominate in the newborn whilst neurological symptoms, such as stroke, seizures or hydrocephalus occur more commonly in infants and older children. Approximately one third of AVMs in childhood present acutely. Radiological investigations, e.g., CT scan, MRI and cerebral angiography are essential to identify the precise location of the lesion. Therapeutic intervention in the acute presentation may involve craniotomy for evacuation of haematoma and treatment of increased intracranial pressure (ICP). Control of seizures and congestive heart failure may take priority and allow time to plan the elective procedures of embolization and surgical excision of the AVM. Operative intervention is hazardous and peroperative complications can be expected in more than 50% of patients. The morbidity and mortality associated with cerebral AVM are high, especially in infants who present in the neonatal period with congestive cardiac failure. The overall mortality in this series was 20%. Children presenting with intracranial arteriovenous malformations require a multidisciplinary approach. The successful management of anaesthesia either for embolization or surgical resection necessitates an understanding of the disciplines of paediatric and neuroanaesthesia. Special care and specific attention to detail may contribute to reduce the high morbidity and mortality encountered in these compromised children. PMID- 8004741 TI - Congenital laryngomalacia. AB - There is at present, very little information on congenital laryngomalacia in the anaesthetic literature. The purpose of this article is to review this topic, which in 90% of patients represents a benign self-limiting condition, disappearing by the age of two to five years. However, if untreated, the remaining 10% of cases can prove fatal. This severe form presents as persistent sternal recession, feeding difficulties, and failure to thrive, progressing to apnoeic attacks, cor pulmonale and eventually death. The developmental and functional anatomy of the larynx will be included, with a discussion of the pathophysiology and history of the disorder. Its diagnosis and a resume of the various treatment strategies, will be presented. The anaesthetic management is controversial as is the surgical technology. Our technique, for diagnosis or definitive repair, is based upon suspension laryngoscopy using topical local analgesia and spontaneous ventilation. Halothane is then administered by insufflation into the pharynx, using a #8 nasopharyngeal catheter, and suction is applied to the mouth. During the surgical repair, an endotracheal tube (ETT), may be inserted, at the discretion of the anaesthetist and surgeon. Finally, the role of the dioxide CO2 laser and its hazards will be introduced. PMID- 8004742 TI - Mechanisms of inhibition of endothelium-dependent relaxation by halothane, isoflurane, and sevoflurane. AB - Volatile anaesthetics inhibit endothelium-dependent relaxation, but the underlying mechanism(s) have not been clarified. In an attempt to elucidate the mechanism(s), we determined the effects of halothane, isoflurane and sevoflurane on relaxation induced by acetylcholine and sodium nitroprusside (SNP) and the cGMP formation elicited by exogenous nitric oxide (NO) and SNP in rat aortas. Acetylcholine (10(-7)-10(-5) M)-induced relaxation was attenuated by halothane (2%), isoflurane (2%) and sevoflurane (4%). SNP (10(-8) M)-induced relaxation was reduced by halothane (2%), but not by isoflurane (2%) or sevoflurane (4%). The cGMP level of NO-stimulated aorta was reduced by halothane (2%) and sevoflurane (4%), but not by isoflurane (2%). The cGMP level of SNP (10(-7) M)-stimulated aorta was reduced by halothane (2%), but not by isoflurane (2%) and sevoflurane (4%). We conclude that the mechanisms responsible for the inhibition of endothelium-dependent relaxation differ among anaesthetics. Isoflurane inhibits the relaxation mainly by inhibiting the formation of NO in the endothelium. In contrast, the effect of halothane on endothelium-dependent relaxation may be largely due to the inhibition of action of NO in the vascular smooth muscle and the effect of sevoflurane may be to inactivate NO or to inhibit the action of NO. PMID- 8004743 TI - [The effects of halothane on the changes in PaCO2, acid-base equilibrium and ventilation induced by hypoxia in the rat]. AB - The effects of progressive hypoxia, obtained by decreasing FIO2 from 0.21 to 0.12, on arterial blood gases and acid-base balance were studied in 13 awake rats and 13 rats anaesthetized with halothane (inspired concentration 1.1%). The effects on ventilation of the decrease in FIO2 from 0.21 to 0.12 were studied in eight rats, awake and then anaesthetized. Halothane causes a decrease in PaO2 and an increase in PaCO2; it abolishes the ventilatory response to hypoxia. The effects of hypoxia on PaCO2 were identical in awake and in anaesthetized rats. In the awake rats, PaO2 decreased from 90.3 +/- 5.9 mmHg to 42.3 +/- 3.6 mmHg, and PaCO2 decreased from 36.7 +/- 3.3 mmHg to 28.1 +/- 1.8 mmHg. In the anaesthetized rats, PaO2 decreased from 78.8 +/- 6.2 mmHg to 34.8 +/- 4.2 mmHg, and PaCO2 decreased from 40.7 +/- 2.8 mmHg to 31.9 +/- 3.7 mmHg. The decrease in PaCO2 during acute hypoxia in the anaesthetized rat could be explained by a decrease in CO2 production, secondary to a decrease in oxygen consumption due to the metabolic and circulatory effects of halothane and hypoxia. PMID- 8004745 TI - Children and size of laryngeal masks. PMID- 8004744 TI - History of Canadian anaesthesia. Samuel Johnston (1868-1946). PMID- 8004746 TI - End tidal O2 and CO2 after resuscitation. PMID- 8004748 TI - Aortocaval compression. PMID- 8004747 TI - Malignant hyperthermia during isoflurane anaesthesia. PMID- 8004749 TI - Epidural catheter entrapment. PMID- 8004750 TI - Antitumor activity of halogen analogs of phosphoramide, isophosphoramide, and triphosphoramide mustards, the cytotoxic metabolites of cyclophosphamide, ifosfamide, and trofosfamide. AB - A series of halogen analogs of phosphoramide mustard, isophosphoramide mustard, and triphosphoramide mustard, the cytotoxic metabolites of the antitumor drugs cyclophosphamide, ifosfamide, and trofosfamide, respectively, was evaluated in vitro against human tumor cell lines and in vivo against experimental tumors to investigate the effect of replacement of chlorine with bromine or fluorine on the antitumor activity of the parent phosphoramide mustards. In the experimental tumors L1210 leukemia, B16 melanoma, mammary adenocarcinoma 16/C, and ovarian sarcoma M5076, the antitumor activity of the analogs was observed to be generally comparable with that of the parent mustards when chlorine was replaced by bromine but uniformly lower when chlorine was replaced by fluorine. Furthermore, the monobromo analog of isophosphoramide mustard displayed equal or somewhat greater activity in comparison with cyclophosphamide when evaluated against subcutaneously implanted L1210 leukemia with intraperitoneal drug treatment and against mammary adenocarcinoma 16/C. PMID- 8004751 TI - Quantitation of cell-associated doxorubicin by high-performance liquid chromatography after enzymatic desequestration. AB - A method for measuring cellular concentrations of the anthracycline doxorubicin was developed. The assay involves cell lysis and protein degradation by detergent and proteinase K treatment followed by DNA hydrolysis using DNase I. Prior to high-performance liquid chromatography, samples are deproteinized by the addition of ZnSO4 and methanol. The assay is linear with respect to both the cellular drug content and the number of cells assayed over the ranges tested, and drug recovery is close to 100%. The method has a limit of detection of 50 fmol injected doxorubicin. Within run and between-day coefficients of variation have consistently been found to be in the 5% and 10% range, respectively, in different cell lines exposed to doxorubicin in vitro. The method has been evaluated in analyses of doxorubicin levels in mononuclear blood cells of patients. The assay offers several advantages over commonly used organic extraction techniques and may improve cellular drug monitoring during anthracycline therapy in patients. PMID- 8004752 TI - Expression of glutathione-S-transferases alpha and pi in gastric cancer: a correlation with cisplatin resistance. AB - Glutathione-S-transferase (GST) in one of several factors that are proposed to affect tumor sensitivity to anticancer drugs, including cisplatin (CDDP). Attempts are made herein to evaluate the significance of the enzymes in resistance to CDDP in clinical samples of gastric cancer. A total of 22 gastric cancer specimens, 16 of which were obtained with matching normal mucosae, underwent immunoblotting with polyclonal antibodies against GST-alpha and GST-pi. At the same time, the chemosensitivity of 15 gastric cancer specimens to CDDP was evaluated by the succinic dehydrogenase inhibition (SDI) test. The expression of GST-pi was detected in all the specimens, and its content in the neoplasms exhibited a significant positive correlation with that in the matched normal mucosae. The expression of GST-alpha was detected in 18 of 22 cancer specimens (82%), but its content in the neoplasms did not correlate with that in the matched mucosae. A comparison of the drug-sensitivity findings with the results of immunoblotting revealed a weak but interesting correlation between the protein levels of GST-alpha and CDDP resistance. The cellular content of GST-alpha correlated weakly with CDDP resistance in gastric cancer, and its quantification could contribute to prediction of the clinical effects of CDDP in patients with gastric cancer. PMID- 8004753 TI - Methotrexate and 6-mercaptopurine maintenance therapy for childhood acute lymphoblastic leukemia: dose adjustments by white cell counts or by pharmacokinetic parameters? AB - In a consecutive study of 14 boys and 17 girls with non-B-cell ALL who were > or = 1 year of age at diagnosis, the degree of myelosuppression during the last year of MTX/6MP maintenance therapy was analyzed in relation to the erythrocyte concentration of MTX polyglutamates and 6-thioguanine nucleotides (E-MTX and E 6TGN, the respective major cytotoxic metabolites of MTX and 6MP). For each patient, E-MTX and E-6TGN levels were measured 2-15 (median, 6) and 2-17 (median, 7) times, respectively. From these measurements, arithmetic means of E-MTX and E 6TGN were calculated (mE-MTX and mE-6TGN, respectively). Since MTX and 6MP probably work synergistically, the product of mE-MTX and mE-6TGN was calculated for each patient (mE-MTX x 6TGN). The degree of myelosuppression was registered as the mean WBC determined following cessation of the therapy minus the mean WBC measured during the therapy (mWBCshift). The mean WBCs measured on therapy (mWBC(on)) and off therapy were highly correlated (r = 0.48, P = 0.009). The median mWBCshift was 2.7 x 10(9)/l (range, 1.4-4.8 x 10(9)/l). In a multivariate regression analysis, the best-fit model to predict the mWBCshift included mE-MTX x 6TGN, age at drug withdrawal, and mWBC in the order given [mWBCshift = 4.3 + 0.00089 x (mE-MTX x 6TGN) - 0.097 x age - 0.41 x mWBC(on); global rs = 0.66, P = 0.0002]. Thus, the patients with higher mE-MTX x 6TGN values, the younger patients, and the patients with the lowest WBC during therapy had the most pronounced degree of myelosuppression as measured by mWBCshift. These results indicate that E-MTX and E-6TGN may give a better reflection of the treatment intensity than do the WBCs alone. PMID- 8004754 TI - Novel lowly immunosuppressive antitumor fluorouridine derivative, UK-21: antitumor activity and effect on humoral immune response in mice. AB - Our previous studies indicated that a newly synthesized 5-fluorouridine derivative, 2',3',5'-tris-O-[N-(2-n-propyl-n-pentanoyl)glycyl]-5-fluorouridine (UK-21), revealed its antitumor activity by being converted to 5-fluorouridine (5 FUR) and showed a low level of immunological side effects. However, the bioavailability of UK-21 given orally did not seem to be good. In the present study, we focused on the antitumor and immunosuppressive activities of UK-21 given i.p. to mice. UK-21 suppressed the growth of L-1210, P388 and EL4 leukemias inoculated i.v. into corresponding syngeneic mice and both the growth of Lewis lung carcinoma transplanted s.c. and its subsequent metastasis to the lung. UK-21 showed antitumor activity at doses almost 10 times lower than those of 5 fluorouracil (5-FU). The side effects of UK-21, especially on immune functions, were examined in comparison with those of 5-FUR, 5-FU, and cyclophosphamide (CY) at doses producing comparable antitumor activity. The suppressive effect of UK-21 on IgM and IgG antibody formation in mice immunized with ovalbumin was clearly weaker than that of 5-FUR, 5-FU, and CY. The suppressive effect of UK-21 on thymus weight was markedly weaker than that of 5-FU and CY. The reduction of WBC counts induced by UK-21 was also lower than that produced by any other agent. The results reported herein suggest the strong possibility of UK-21 being developed as a novel anticancer drug with cytotoxic mechanisms different from those of 5 FU. Our study also points to the chemical modification of 5-FUR as a feasible way of developing new anticancer drugs. PMID- 8004755 TI - Biological activity of a novel rationally designed lipophilic thymidylate synthase inhibitor. AB - AG-331 (N6[4-(N-morpholinosulfonyl)benzyl]-N6-methyl-2,6-diamino- benz[cd]indole glucuronate) is a novel lipophilic thymidylate synthase (TS) inhibitor. The properties of this compound were investigated in H35 rat hepatoma cells and in three variant cell lines resistant to antifolates by differing mechanisms. There was no evidence for any intracellular effect of AG-331 on dihydrofolate reductase (DHFR); however, the low degree of cross-resistance found for the H35FF line, which has elevated TS levels, suggested that TS may not be the sole locus of action of AG-331 in hepatoma cells. TS-directed effects of AG-331 were suggested by the pattern of its inhibition of deoxyuridine incorporation into DNA and the lesser effects of purine incorporation. In addition, H35 cells treated with 10 microM AG-331 were shown to accumulate in the S phase of the cell cycle, and this effect could be reversed by coadministration of thymidine. However, when treatments were conducted at a 5-fold higher concentration of AG-331, no S-phase block was apparent, suggesting the loss of a TS-directed effect at high inhibitor concentrations. Thymidine and folinic acid also failed to protect cells against AG-331 cytotoxicity, suggesting an alternate mode of action. Similar results were also obtained in protection experiments with a human hepatoma cell line, HEPG2, although previous results obtained in colon- and breast-cancer cell lines have suggested TS specific effects for AG-331. The possibility that biotransformation of AG-331 to other toxic species may occur in liver-derived cell lines has yet to be investigated. PMID- 8004756 TI - Liposomal palmitoyl-L-asparaginase: characterization and biological activity. AB - A new derivative of L-asparaginase, palmitoyl-L-asparaginase (palmitoyl-L ASNase), has been incorporated in liposomes. For this purpose we modified the dehydration-rehydration method and optimized the liposomal composition. The pharmacokinetics, toxicity, and in vivo antitumor activity against P1534 lymphoma of different liposomal palmitoyl-L-ASNase formulations were studied. Liposomal encapsulation of palmitoyl-L-ASNase as compared with free palmitoyl-L-ASNase resulted in a prolongation of the blood half-life (from 2.88 h to longer than 23.7 h), abrogation of acute toxicity, and preservation of in vivo antitumor activity. PMID- 8004757 TI - In vivo modulation of several anticancer agents by beta-carotene. AB - The ability of the collagenase inhibitor minocycline and of beta-carotene to act as positive modulators of cytotoxic anticancer agents was assessed in vitro and in vivo. Cell-culture studies were conducted using the human SCC-25 squamous carcinoma cell line. Simultaneous exposure of the cells to minocycline and beta carotene or 13-cis-retinoic acid along with cisplatin (CDDP) resulted in a small decrease in the cytotoxicity of the CDDP. The addition of each of the modulator combinations for 1 h or 24 h to treatment with melphalan (L-PAM) or carmustine (BCNU) resulted in greater-than-additive cytotoxicity with each of four regimens. The modulator combinations of minocycline and beta-carotene applied for 1 h or 24 h and the modulator combination of minocycline and 13-cis-retinoic acid produced greater-than-additive cytotoxicity at 50 microM 4-hydroperoxycyclophosphamide (4 HC), whereas minocycline and 13-cis-retinoic acid applied for 1 h was antagonistic with 4-HC and the other modulator treatments at low concentrations of 4-HC resulted in subadditive cytotoxicity. The effect of treatment with beta carotene alone and in combination with several different anticancer agents was examined in two murine solid tumors, the FSaII fibrosarcoma and the SCC VII carcinoma. Administration of the modulators alone or in combination did not alter the growth of either tumor. Whereas increases in tumor growth delay occurred with the antitumor alkylating agents and beta-carotene and with minocycline and beta carotene, a diminution in tumor growth delay was produced by 5-fluorouracil in the presence of these modulators. The modulator combination also resulted in increased tumor growth delay with adriamycin and etoposide. Tumor-cell survival assay showed increased killing of FSaII tumor cells with the modulator combination and melphalan or cyclophosphamide as compared with the drugs alone. These results indicate that further investigation of this modulator strategy is warranted. PMID- 8004758 TI - Reduced levels of topoisomerase II alpha and II beta in a multidrug-resistant lung-cancer cell line. AB - We have previously shown that the doxorubicin-selected multidrug-resistant small cell lung-cancer cell line H69AR is resistant to VP-16-induced single-strand DNA breaks as compared with its parental H69 cell line. Levels of immunoreactive topoisomerase II alpha are also reduced in H69AR cells. In the present study, we found that cleaved complex formation in the presence of VP-16 was decreased in H69AR cells as compared with H69 cells. In addition, the resistant cells contained lower levels of both topoisomerase II alpha and topoisomerase II beta protein and mRNA. However, these changes were not accompanied by a decrease in the P4-unknotting (strand-passing) activity of 0.67 M NaCl nuclear extracts of H69AR cells, nor was there any difference in VP-16 inhibition of unknotting activity in the H69 and H69AR nuclear extracts. These data suggest that reduced levels of topoisomerase II alpha and II beta may contribute to the resistance of H69AR cells to VP-16 and other drugs that target these isoenzymes. PMID- 8004760 TI - Effect of mitomycin C, verapamil, and hyperthermia on human gastric adenocarcinoma. AB - The purpose of this study was to assess the efficacy of verapamil (20 microM) and hyperthermia (42 degrees C) as modifiers of mitomycin C (MMC), used at different concentrations, in inhibiting the growth of human gastric adenocarcinoma (AGS) cells. Combined verapamil and hyperthermia treatment resulted in a significant decrease in cell count by 72.2% as compared with the control value. Verapamil drastically enhanced the growth-inhibitory activity of MMC at high concentration against AGS cells by 67.5% and had no effect at intermediate and low concentrations. Hyperthermia did not enhance the effect of MMC on AGS cells. The modalities analyzed in this study require further investigation and may have potential for in vivo studies on gastric cancer therapy in the near future. PMID- 8004759 TI - Quantification of topoisomerase-DNA complexes in leukemia cells from patients undergoing therapy with a topoisomerase-directed agent. AB - Several clinically important drugs utilized in cancer chemotherapy inhibit type I (Topotecan) or type II (amsacrine, etoposide) DNA topoisomerases by stabilizing the formation of DNA-topoisomerase complexes (topoisomerase-DNA cross-links). In various cell lines, the magnitude of drug-induced DNA-protein cross-link production correlates with the magnitude of cytotoxicity induced by the drugs. We developed a simple filter-binding assay that can measure drug-induced DNA-protein cross-links in leukemia cells obtained directly from patients because the assays most widely used for assessment of drug-induced DNA-protein cross-links in cells [sodium dodecyl sulfate (SDS)/KCl precipitation and alkaline elution] are not readily applicable for use on patient material. HL-60 human leukemia cells or freshly isolated patients' leukemia cells were incubated with Topotecan, etoposide, or amsacrine; lysed with SDS; and applied to nitrocellulose filters in a low-salt buffer. DNA is retained on the filter only if it is covalently bound to protein. The amount of DNA retained on the filter is quantified by hybridization to the alu sequence of DNA, which is distributed ubiquitously in the human genome. Using radiolabeled cells, we compared the filter-binding assay directly with the SDS/KCl precipitation assay in the detection of etoposide- or amsacrine-induced DNA-protein cross-links in HL-60 cells and amsacrine-resistant HL-60/AMSA cells. Both the SDS/KCl precipitation assay and the filter-binding assay detected etoposide-induced DNA-protein cross-links in HL-60 and HL-60/AMSA cells and detected a greater frequency of amsacrine-induced DNA-protein cross links in HL-60 cells than in HL-60/AMSA cells. The filter-binding assay detected DNA-protein cross-links in freshly isolated leukemia cells exposed to Topotecan in vitro. The ratios of DNA retention for Topotecan-treated versus untreated cells from leukemia patients ranged from 1.8 to 11.5. The heterogeneity of this detected cross-linking was as might be expected if the assay were predictive of the antileukemic action of Topotecan, which is variable. This new filter-binding technique may be useful for predicting the sensitivity of individual patients' tumors to drugs that inhibit type I or type II DNA topoisomerases. PMID- 8004761 TI - Phase I and pharmacokinetic evaluation of floxuridine/leucovorin given on the Roswell Park weekly regimen. AB - A phase I and pharmacokinetics study was carried out of floxuridine (FdUrd) modulated by leucovorin (LV) given on the Roswell Park regimen (LV given at 500 mg/m2 by 2-h infusion and FdUrd given by i.v. push at 1 h after the start of LV infusion, treatment being given weekly x 6). The dose-limiting toxicity was diarrhea; the MTD and recommended dose for phase II studies was 1,650 mg/m2 per week of FdUrd. The dose-response curve was steep, with 3/3 patients treated at a dose of 1,750 mg/m2 developing grade IV diarrhea. With this schedule there was no significant mucositis. Pharmacokinetic parameters showed very wide interpatient variability. Plasma decay was biphasic with a t1/2 beta of approximately 2 h. Plasma clearance was high (> 200 1 h-1). No correlation between pharmacokinetic parameters and toxicity could be identified. PMID- 8004762 TI - Phase II trial of echinomycin in patients with advanced or recurrent colorectal cancer. AB - Echinomycin is a novel bifunctional intercalating agent derived from Streptomyces echinatus. A phase II clinical trial of echinomycin in patients with advanced, measurable colorectal cancer was initiated to determine the efficacy and toxicities of this agent. Echinomycin, 1.5 mg/m2, was given initially as a 30- to 60-min infusion every 4 weeks. After 4 episodes of anaphylaxis had occurred among the first 14 patients, the schedule was changed to a 24-h infusion, and an additional 16 patients were treated on this schedule. Treatment was given every 3 weeks. A total of 30 patients were eligible and evaluable; there were 3 (10%; 90% confidence interval, 3%-23%) clinical responses lasting 3, 3+, and 12 months, respectively. The most serious toxicity encountered was anaphylaxis, which occurred in 5 patients, although with no serious sequelae. A premedication regimen with dexamethasone, diphenhydramine, and cimetidine and a change of the duration of the infusion to 24 h reduced the incidence of this complication. Grade 2-3 vomiting occurred among earlier patients treated; however, with the 24 h schedule this toxicity was substantially reduced. The sole important case of hematologic toxicity was a single patient with grade 3 thrombocytopenia. Echinomycin employed in this dose and schedule had modest activity against colorectal cancer, comparable with that observed with 5-fluorouracil. Further studies in patients with gastrointestinal malignancies using a 24-h infusion with a dexamethasone premedication regimen similar to that employed prior to administration of taxol may be warranted. PMID- 8004763 TI - Marker rhythms for chronotherapy of cancer. PMID- 8004764 TI - Differential development of binding sites of two lectins in the vomeronasal axons of the rat accessory olfactory bulb. AB - Binding of fluorochrome-conjugated lectins, Bandeiraea simplicifolia lectin-I (BSL-I) and Vicia villosa agglutinin (VVA), to the vomeronasal axons was investigated in the accessory olfactory bulb (AOB) of developing rats at embryonic day (E) 16, 18, and 20, and postnatal day (P) 0, 3, 7, 14, and 28. Intense fluorescence for VVA was first observed at E18, and the position-specific binding pattern observed in adults was established at P0; intense fluorescence for VVA was observed in the posterior 2/3 of the vomeronasal nerve layer (VNL) and glomerular layer (GL) and weak fluorescence was present in the anterior 1/3 of these layers. Fluorescence for BSL-I was observed in the posterior half of VNL and GL at P0; the area bound with BSL-I was expanded to the anterior area and intensity of the fluorescence increased as the development proceeded. At P28, binding of BSL-I was observed in the entire VNL and GL as identical to adults. These results indicate that the binding sites of BSL-I and VVA in the vomeronasal axons at the level of rat AOB develop differentially during ontogeny, suggesting that rat VN axons consist of two subpopulations expressing different glycoconjugates. PMID- 8004765 TI - Ontogenesis of the angiotensin II (ANGII) receptor system in the duck brain. AB - The ontogenetic development of the central nervous angiotensin II (ANGII) receptor system in the duck was studied at embryonic days E20 and E27 and at postnatal days P3 and P14 by computerized semiquantitative autoradiography employing the receptor antagonist 125I[1Sar,8Ile]ANGII as radioligand. For circumventricular structures involved in the sensing of brain-intrinsic (AV3V region) or blood-borne (subfornical organ, SFO) ANGII, binding sites for 125I[1Sar,8Ile]ANGII were first detectable at E27, with a steady rise in binding density up to P14. The choroid plexus of the lateral (PCVL) and third (PCVIII) cerebral ventricles responsible for cerebrospinal fluid (CSF) production were endowed with maximal ANGII receptor densities at E20 with subsequent reduction to constant medium (PCVIII) or low (PCVL) values. Besides the choroid plexus, the magnocellular paraventricular nucleus (PVN) was the only structure presenting ANGII specific binding sites at E20, although at low density. As for the SFO and AV3V region, labelling of ANGII binding sites in the PVN increased continuously during development to high values at P14. Nuclear components of the limbic system (archistriatum, amygdala and habenular complex) did not reveal specific labelling by the radioligand at E20 with constant, moderate binding densities evaluated for E27, P3 and P14. In the duck brain, functionally related structures exhibited a homogeneous ontogenetic development of their ANGII receptor system. PMID- 8004766 TI - Cholinergic modulation through biogenic amines during development of the chick spinal cord. AB - Our previous analyses of the functional maturation of cholinergic neurotransmission in the chick embryo spinal cord showed that 12 days of development represents a crucial stage in the maturation of cholinergic neurotransmission. Since supraspinal inputs are essential for the modulation of motoneuron activity in the embryo, we studied, using a pharmacological approach, the regulatory effects of biogenic amines on the developing cholinergic neurotransmission. We show that, in spite of the early occurrence of serotonin and norepinephrine in the developing spinal cord, the modulatory influences of these biogenic amines on motoneurons can only be effective from 12 days of incubation onwards. It also appears that the inputs of biogenic amines on cholinergic activity is a sequential event. Whereas serotonin (5-HT) begins to stimulate cholinergic activity from 12 days of incubation, norepinephrine inputs are only observed at later stages (17 days of development). These observations underline the specific turning point in the functional maturation of motoneurons, we noted in our previous studies. At the end of embryonic life a specific interrelationship between the biogenic amines was noted, its effect on the cholinergic system may lead to a more precise motor control, preparing the chick embryo for hatching. PMID- 8004767 TI - Complex patterns of [125I]omega-conotoxin GVIA binding site expression during postnatal rat brain development. AB - In the mature CNS, N-type calcium channels regulate neurotransmitter release. The role of these channels in developing brain is less clear. Study of [125I]omega conotoxin GVIA binding sites in developing rat brain using autoradiography reveals that putative N-type channels appear and disappear in complex temporal spatial profiles including: (1) gradual increase to adult levels (cerebral cortex); (2) substructure differentiation (cerebellum); (3) transient expression (pons); and, (4) selective depletion (medulla). Transient expression of N-type calcium channels may influence specific neurodevelopmental processes. PMID- 8004768 TI - Astrocytic glycogenolysis energizes memory processes in neonate chicks. AB - In previous pharmaco-behavioural experiments, we have shown that three sequential stages can be distinguished in discrimination memory for a single trial passive avoidance experience in neonate chicks: a short-term (STM) stage, available for 10 min following learning; an intermediate (ITM) stage, operating between 20 and 50 min (ITMB) post-learning; and a long-term (LTM) stage formed by 60 min after learning. The ITM stage can be divided into two parts: a first phase (ITMA) which is susceptible to inhibition by the uncoupler of oxidative phosphorylation (and thus of oxidative metabolism), 2,4-dinitrophenol (DNP), and a second DNP insensitive phase (ITMB). ITMA occurs between 20 and 30 min post-training and ITMB between 30 and 50 min. In the present study we have shown: (1) that day-old chicks trained in the passive avoidance task and immediately thereafter injected with the glycolytic inhibitor iodoacetate show retention deficits that are first evident 30 min post-training, and (2) that glycogenolysis, i.e. breakdown of glycogen, a high-molecular carbohydrate energy store localized in astrocytes, occurs in the forebrains of trained, but otherwise untreated birds, between 35 and 55 min after learning. These findings strongly suggest that glycolysis, including astrocytically localized glycogenolysis, is essential to provide energy for active processes occurring during ITMB and that these processes are indispensable for subsequent development of long-term memory. PMID- 8004769 TI - Evidence that weaning stimulates the developmental expression of a delta-opioid receptor subtype in the rat. AB - To study whether weaning stimulates the development of a subtype of the delta opioid receptor we have measured antinociceptive activity of putative delta 1 (DELT I) and delta 2 (DSLET) agonists in weaned and non-weaned 25-day-old rats. In weaned rats, DSLET produced antinociception reversed by the delta 2-antagonist naltriben, but in non-weaned rats DSLET had no effect. Responses to DELT I were evident in both weaned and non-weaned rats and were not antagonised by naltriben. This is the first evidence that delta-receptor subtypes develop independently and suggests that weaning is the stimulus for the expression of the delta 2-subtype. PMID- 8004770 TI - Characteristics of gangliosides including O-acetylated species in growth cone membranes at several developmental stages in rat forebrain. AB - Growth cones, the motile tips of extending neuronal processes, are involved in accurate synaptogenesis. To study the developmental changes in ganglioside composition including O-acetylated gangliosides in growth cones, we analyzed the gangliosides in growth cone membranes (GCM) prepared from rat forebrains at different developmental stages. At several stages, GCM contained significantly larger amounts of gangliosides than the other membrane subfractions. The ganglioside content of GCM increased in amount with development. Moreover, in GCM, the relative amount of GD3 gradually decreased, and that of GD1a dramatically increased. There were significant differences in the composition of ganglioside species between GCM and the perinuclear plasma membrane subfraction (NM); most importantly, GCM had a higher ratio of GD1a to GM3 plus GD3 than NM. There were three different O-acetylated gangliosides in GCM: O-acetyl-GD3, O acetyl-GT1b, and O-acetyl-GQ1b. The molar ratio of O-acetyl-GD3 decreased in GCM at later stages (5% of the total gangliosides at embryonic day 17, to 1% at postnatal day 5). However, those of the other two O-acetylated gangliosides were almost constant (1-2% of the total). Our results show that there are significant differences in ganglioside content and composition between the membrane subfraction of growth cones and the perinuclear portion. This suggests that several species of gangliosides, including O-acetyl-GD3, play a role in growth cone function. PMID- 8004771 TI - Early ultrastructural changes in blood-brain barrier vessels of the rat embryo. AB - The blood-brain barrier (BBB) in fetal rat brain has been shown by others to be more permeable to a variety of blood-borne solutes than the BBB in adults. We used ultrastructural morphometric methods to measured the density of putative vascular pores between the ages of embryonic day (E) 11 and birth to determine the structural basis for this relatively high permeability. We found that fenestrations, that are frequent at E11, declined rapidly and were last seen at E13 in intraparenchymal vessels and at E17 in pial vessels. Interendothelial junctions in fetal brain contained expanded clefts suggestive of paracellular channels at all ages examined, although they disappear after birth. Both of these features likely contribute to high fetal BBB permeability, but endothelial vesicles probably do not. The central nervous system is vascularized by ingrowth of capillary sprouts from the perineurial vascular plexus. Invading capillaries express BBB features in response to inductive signals from the surrounding neural tissue. We compared early ultrastructural changes in perineurial vessels, which are separated from neural tissue by a sizeable perivascular space, with those in intraneural vessels, which are totally enveloped by neural tissue, to determine whether the inductive interaction requires close cellular contact. For the most part, the perineurial and intraneural vessels matured in parallel. Furthermore, cerebellar vessels developed in parallel with cerebral vessels, even though they did not invade neural tissue until a comparatively late stage. These results suggest that intimate contact between neural tissue and vessel walls is not a requirement for BBB expression. PMID- 8004772 TI - C-CAM expression in the developing rat central nervous system. AB - C-CAM, a transmembrane glycoprotein belonging to the immunoglobulin superfamily, can mediate intercellular adhesion by homophilic, Ca(2+)-independent binding. Immunohistochemical analysis of adult rat tissues has demonstrated that C-CAM is expressed in various epithelia, vessel endothelia, and hematopoietic cells. By molecular cloning and sequence analysis several isoforms differing both in the extracellular and the cytoplasmic domains have been found. Here we have analyzed the expression of C-CAM in the developing rat central nervous system. No neuronal expression was observed, but biochemical and immunohistochemical analyses demonstrated that C-CAM becomes expressed in the microvessels from embryonic day E-13; the intensity of the staining increased through day E-15 and then gradually decreased during the perinatal and early postnatal period. The expression of C CAM in the walls of the microvessels was confirmed by in situ hybridization. Immunoelectron microscopy showed that C-CAM was localized both to the abluminal surface of the endothelial cells and to cellular processes of primordial pericytes where these two cell types are in contact with each other. No staining was found on the luminal endothelial cell surfaces or inter-endothelial cell contact areas. During the perinatal period C-CAM also became expressed on the opposite side of the pericytes and on other cells, possibly astrocytes, in contact with these areas of the pericytes. These observations suggest that C-CAM may be involved in heterotypic, homophilic adhesion between endothelial cells, pericytes and astrocytes, and in maturation of the vessel walls. PMID- 8004773 TI - Neurogenesis of spinothalamic and spinocerebellar tract neurons in the lumbar spinal cord of the rat. AB - The temporal and spatial neurogenic patterns of spinothalamic and spinocerebellar neurons were determined in spinal cord segment L1 of the rat. Neurogenic patterns were demonstrated with [3H]thymidine administered to fetal rats during the period when neurons with supraspinal projections are known to be generated, i.e. on one of embryonic (E) days E13, E14, or E15. The animals were allowed to survive 50 to 100 days postpartum, then neurons with spinothalamic and spinocerebellar projections were retrogradely filled with fluorescent axonal tracers, Fluoro-Gold or True blue, which were pressure injected into the dorsal thalamus and cerebellum in various combinations in the same and in separate animals. Neurons labeled with each retrograde tracer and [3H]thymidine and neurons labeled with retrograde tracers alone were counted in spinal cord segment L1 in each of the animals. Spinothalamic and spinocerebellar neurons were found to be separate and distinct populations. Statistical analysis of the data showed that spinothalamic and spinocerebellar neurons also have distinctly different patterns of neurogenesis which suggest early determination in each cell line. The temporal neurogenic pattern followed a projection-distance gradient, such that spinothalamic neurons, which have longer axons than spinocerebellar neurons, completed neurogenesis prior to spinocerebellar neurons in each region of the spinal gray. PMID- 8004774 TI - Ontogeny of sex differences among newly-generated neurons of the juvenile avian brain. AB - In zebra finches, only males sing and brain regions controlling song exhibit sex differences in neuron number that stem from actions of estrogen during a critical developmental period. In certain song nuclei, these dimorphisms emerge long after neurogenesis and migration are complete, and estrogen promotes masculinization by preventing the death of well-differentiated neurons. But in another region, the higher vocal center (HVC), cellular mechanisms underlying sex differences in neuron number are not so well understood. In the HVC, neurogenesis continues throughout the post-hatch period of sexual differentiation, and sex differences arise during this time because neuron number increases in males but not females. We used [3H]thymidine autoradiography to establish when sex differences in neuron number first develop among a small group of HVC neuronal cohorts. We report that HVC neurons labeled by [3H]thymidine on days 15 and 16 after hatching are sexually dimorphic in number within 10 days of their birth, even before all cells in this cohort complete their migration and/or differentiation. This suggests that the cellular mechanisms contributing to sex differences in neuron number in the HVC may differ from those in other sexually dimorphic neural regions of the vertebrate nervous system. In addition, we found that although many thymidine labeled HVC neurons ultimately project to the robust nucleus of the archistriatum (RA), a sexually dimorphic target, sex differences in their number develop before this efferent projection is established. These results have important implications regarding the site(s) of hormone action, since they suggest that sexual differentiation acts on certain HVC neurons before they establish their efferent projections, and perhaps even before they arrive within the HVC. PMID- 8004776 TI - Axonin 1 is expressed primarily in subclasses of avian sensory neurons during outgrowth. AB - A 120 kDa protein, which is expressed mainly on the surface of chick sensory neurons during outgrowth, was identified by monoclonal antibody 1A12. Crossreactivity studies showed that this protein was identical to axonin 1, a member of the immunoglobulin superfamily which promotes neurite outgrowth. Using the 1A12 antibody, we show that in the peripheral nervous system of the chick, axonin 1 is present on the cell bodies and processes of cutaneous and visceral neurons, but not on muscle afferents. In the central nervous system, axonin 1 is present in sensory pathways, such as fibers of the dorsal funiculi in the spinal cord and the optic pathway. However, axonin 1 is only expressed on growing nerve fibers. Late in embryonic development, it is present only on a small population of dorsal root ganglion cells, and is entirely absent on optic fibers. The disappearance of axonin 1 in the visual pathway coincides with the arrival of optic axons at the tectum, suggesting its expression is down regulated by axonal contact with its target. The localization of this protein on the surface of neuronal membranes was confirmed by EM immunohistochemistry and by labeling live nerve cells and their processes in tissue culture. The restricted spatio-temporal expression of axonin 1, together with its expression on the surface of neuronal membranes suggests that it is important for the development of sensory projections. PMID- 8004775 TI - Children with severe epilepsy: evidence of hippocampal neuron losses and aberrant mossy fiber sprouting during postnatal granule cell migration and differentiation. AB - Surgically resected hippocampi from children with extrahippocampal seizures and structurally non-atrophic brains were examined to determine the relationship of neuron losses and aberrant mossy fiber (MF) sprouting to the postnatal migration and differentiation of the fascia dentata (FD) granule cells (GC). Percent neuron loss compared to age-matched autopsy controls was determined by quantitative cell densities, and aberrant MF sprouting by neo-Timm histochemistry. Postnatal immature GC migration and differentiation was demonstrated by the transient but GC-specific expression of the immature form of neural cell adhesion molecule (NCAM-H). Results showed that the hippocampi from children with seizures appeared microanatomically intact without focal areas of damage. However, significant neuron losses were found by neuron counts in the fascia dentata (P < 0.01), CA4 (P < 0.01), and CA2 (P < 0.05). Aberrant supragranular inner molecular layer MF sprouting was found in hippocampi of children with seizures, and the MFs showed smaller puncta in specimens resected under 2 years of age (n = 3) compared to the larger puncta in older children (n = 5). Hippocampi from children under 2 years of age also demonstrated NCAM-H positive primitive cells in the infragranular and stratum granulosum of the fascia dentata consistent with the postnatal migration and differentiation of GCs, the parent neurons of the MFs. These results indicate that seizures in the immature but structurally intact human hippocampus are associated with decreased neuron densities and aberrant MF sprouting very early in postnatal development. The data also show that aberrant MF sprouting is found during postnatal migration, differentiation and axogenesis of GCs.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8004777 TI - The clinical laboratory is in the information business. AB - Clinical laboratories have always been in the information business. More than ever, this perspective is essential to deal logically with the many current pressures and anticipated changes in laboratory management. Current pressures for test turn-around and report flexibility are readily explained based on the spatial and temporal factors in the information content of a result. A long term trend is apparent toward easier to manage testing systems more often distributed to the point of care. Combined with the trend toward larger and more integrated delivery systems, this increases the need for information management in the laboratory, both to control production of data at many sites and to collect, route, and archive results for each patient. One potential outcome of this trend appears is dispersion of essentially all central hospital laboratory operations to the bedside, the ward based laboratory, or an outside reference lab. These changes will mesh well with the re-design of nursing and ward care jobs underway in the hospital industry which emphasizes cross training of ward personnel and rapid access to services for patient evaluation and monitoring. More than ever, information management will be synonymous with laboratory management. PMID- 8004779 TI - Interpreting the results is the expertise of the laboratory. PMID- 8004778 TI - The role of suppliers and laboratories in the new information environment. PMID- 8004781 TI - Analytical goals for rectilinear calibration functions. AB - Analytical goals for rectilinearity based on within-subject biological variation have not yet been advocated. On the other hand, the statistical tests to evaluate rectilinearity may be too restrictive for clinical purposes. If rectilinearity of the least-squares regression is rejected by the statistical test used, we propose to compare the systematic error introduced using such a regression line as the calibration function, with the allowable total error. Since total error ideally should be less than the within-subject biological coefficient of variation (C.V.Bw) the goal for rectilinearity we propose is that the maximum allowable systematic relative error produced by the calibration function (LoRi) when a lack of rectilinearity really occurs is: LoRi < C.V.Bw -1.96 C.V.M, where C.V.M is the between-run metrological coefficient of variation of the measurement procedure, corresponding to the value of concentration under study. PMID- 8004780 TI - A new case of apo C-II deficiency with a nonsense mutation in the apo C-II gene. AB - The apo C-II gene from a patient with apo C-II deficiency has been sequenced after amplification by the polymerase chain reaction (PCR). The sequence analysis revealed a substitution of adenosine for cytosine at position 3,002 in exon 3, leading to the introduction of a premature stop codon (TAA) at a position corresponding to aminoacid 37 of mature apo C-II. This mutation creates a new Rsa I restriction enzyme site in the apo C-II gene. Amplification of DNA from family members by PCR and digestion with Rsa I established that the patient is a true homozygote for this mutation. The same nucleotide has been substituted for the mutation apo C-IIPadova and apo C-IIBari previously described in two kindreds from Italy. From these data we speculate that base pair 3,002 in the apo C-II gene may represent a hot spot for mutation. PMID- 8004782 TI - Relationship between lipoprotein(a) levels in serum and some indices of protein synthesis in liver cirrhosis. AB - Recent research has demonstrated that the major site of apolipoprotein(a) synthesis, the characteristic protein of lipoprotein(a) (Lp(a)), is the liver and that patients affected by liver cirrhosis have low serum concentrations of Lp(a). Nevertheless, it is still not clear whether Lp(a) behaviour in these patients is related to reduced hepatic protein synthesis, or to decreased serum lipid levels or to both these conditions. In order to investigate further the behaviour of Lp(a) and, in particular, its relationship with some indices of blood lipids and coagulation, 30 patients affected by liver cirrhosis have been studied. Significantly low serum values of Lp(a) were observed in patients with more severe hepatic injury included in classes B and C according to the Child-Pugh score. Lipoprotein(a) was directly correlated with prothrombin plasma activity and with apolipoprotein B-100 and albumin concentrations in serum. This study confirms low serum levels of Lp(a) in cirrhotic patients and suggests that its decrease could be partly due to impaired liver protein synthesis. PMID- 8004783 TI - Genotyping compared with protein phenotyping of the common apolipoprotein E polymorphism. AB - Apolipoprotein E (apo E) genotypes have been determined in 460 Danish men, with the use of the polymerase chain reaction (PCR) to amplify a 244 base pair fragment spanning the first-base polymorphic sites in the codons of amino acids 112 and 158 followed by restriction endonuclease cleavage. The results were compared with the apo E phenotypes previously determined by isoelectric focusing (IEF) of delipidated plasma, not pretreated with neuraminidase, followed by apo E specific immunoblotting. Conflicting results were found in only 9 cases (2.0%) and in each case only with respect to one allele. Five of the discrepancies can be explained, post hoc, by technical difficulties with the IEF method ('faint bands'). A possible cause of the other 4 discrepancies is the presence of rare mutations. Our findings in this large study are reassuring, since, if appreciable and systematic misclassification of genotypes do occur by using IEF, as has been reported from some laboratories, it may influence the validity of genetic epidemiological studies. PMID- 8004784 TI - Serum octadeca-9,11 dienoic acid--an assay of free radical activity or a result of bacterial production? AB - The diene conjugated linoleic acid isomer is currently used as an assay of free radical activity, but recent studies have cast doubt on the specificity of the assay. Therefore, 180 strains of common bacterial lung pathogens were studied to determine whether they could produce the diene conjugated isomer of linoleic acid in vitro. The various strains were grown in tissue culture fluid spiked with linoleic acid. Concentrations of the diene conjugated 18:2 [9,11] linoleic acid isomer and the parent compound, 18:2 [9,12] linoleic acid were then determined using a high performance liquid chromatography method. The percentage molar ratio of these two isomers was found to be significantly elevated in 12.8% of all bacterial strains examined. In contrast the thiobarbituric acid reactivity, a non specific measure of lipid peroxidation, was not elevated in any of the strains incubated in an identical fashion. These results suggest that the diene conjugated linoleic assay may not be a reliable marker of the free radical processes in the lung in the presence of certain bacterial infections. PMID- 8004786 TI - Therapeutic whole-blood levels of cyclosporin A in heart and lung transplantation. AB - The use of cyclosporin A (CyA) as an immunosuppressive drug is limited because of its serious side effects. In order to minimise these toxic side effects while utilising immunosuppressive properties of CyA, the dosage of CyA is generally administered on the basis of the individual CyA whole blood level. Therefore, a frequent determination of CyA whole blood levels is necessary. The aim of our study was to establish therapeutic whole blood levels for patients after heart (HTX) and lung (LuTX) transplantation depending on the interval of time after transplantation. CyA levels were determined by HPLC and by fluorescence polarisation immunoassay (FPIA) with a monoclonal and a polyclonal antibody. Two hundred and ninety-five patients after HTX and 48 patients after LuTX were investigated and patients with rejection and/or pathological kidney and liver function were excluded. No significant differences between the two groups of patients were detected. Therefore, common therapeutic ranges for CyA can be used for adequate immunosuppression for patients after HTX and LuTX. PMID- 8004785 TI - The esters of p-hydroxy-benzoate (parabens) inhibit the release of lysosomal enzymes by mitogen-stimulated peripheral human lymphocytes in culture. AB - An in vitro test was set up to assess the release of lysosomal enzymes from cells and the effect on this process of the commonly used preservatives, parabens. Human peripheral lymphocytes, cultivated in vitro for 24 h in the presence or absence of phytohaemagglutinin (PHA; 5 mg/l), were used. After 1 day of incubation, PHA treatment caused an increased release (from 220 to 500%) of the lysosomal enzymes N-acetyl-beta-D-glucosaminidase, beta-D-glucuronidase, alpha-L fucosidase and alpha-D-galactosidase. This enhancement was analytically reliable, and detectable with 1-5 micrograms of cell protein. Leakage of lactate dehydrogenase (LDH) underwent only a 20% increase on PHA treatment, indicating that the increased release of lysosomal enzymes was presumably due to secretion, not to cell damage. In PHA-stimulated lymphocytes, methyl-, ethyl-, propyl- and butyl-parabens caused a concentration-dependent diminution of the secretion of lysosomal enzymes. Butyl-paraben appeared to be the most potent inhibitor, causing a 45-50% inhibition at 0.06 mmol/l. With the other parabens, the inhibitory effect became statistically significant at about 0.25 mmol/l for alpha L-fucosidase and alpha-D-galactosidase, and at 0.5 mmol/l for N-acetyl-beta-D glucosaminidase and beta-D-glucuronidase. At 1 mmol/l inhibition was greater than 50% for all the enzymes and was more marked with the propyl derivative. Parabens did not influence the release of LDH, suggesting that they affected particularly the secretion of lysosomal enzymes. This supports the hypothesis that parabens are capable of affecting cellular function at concentrations which are likely to be reached in blood or tissues under conditions of common use. PMID- 8004788 TI - HPLC assay of conjugated bile acids in human fluids using on-line sample pretreatment on a standard isocratic chromatograph. AB - A rapid and simple on-line purification procedure was developed for determining the conjugated bile acids in human fluids by high-performance liquid chromatography (HPLC). Biological samples were diluted and directly injected without further treatment onto a pre-column dry-packed with 40-microns octadecylsilica and installed at the injector loop position. After washing the pre-column with 40% methanol in acetate buffer and then with water, the retained compounds were back-flushed by the mobile phase onto the analytical column during the normal course of chromatography. The method was found to be accurate and reproducible. The levels of conjugated bile acids in serum, duodenal bile and gastric juice from patients with hepatobiliary and gastric diseases were determined by on-line pre-column clean-up and reversed-phase HPLC. PMID- 8004787 TI - Erythrocyte Na+,K(+)-ATPase properties and adenylate energy charge in normotensives and in essential hypertensives. AB - The activity and some kinetic properties of RBC Na+,K(+)-ATPase (EC 3.6.1.37) were investigated in essential hypertensives (EH; 40 subjects) and normotensives (NT; 20 subjects). A decrease in ouabain-sensitive 86Rb uptake as well as ouabain sensitive ATPase activity was found in EH. [Na+]i and [K+]i of EH did not show any statistical difference from NT. Na+,K(+)-ATPase showed a reduced Mg2+ activation and the apparent Km value for Mg2+ was 2-fold increased in the EH group. The influence of temperature on the Na+,K(+)-ATPase showed a reduced modulation and a minor activity peak at 37 degrees C in the patients, consequently the calculated activation energy of the enzyme was increased at temperatures lower than 40 degrees C. Increased RBC adenylate energy charge (EC) was observed in EH when compared with NT. A negative correlation between EC and total Na+,K(+)-ATPase activity was found when all subjects were compared and also in both groups, showing a possible pump involvement in the regulation of the RBC metabolic flux in EH. These data provide evidence about some modifications in active Na+,K+ transport and in EC in RBC which allows a further characterization of membrane cation fluxes in EH. PMID- 8004789 TI - Light chains of immunoglobulins in human secretions. AB - Immunoglobulin kappa light chains are predominant in normal human serum and a kappa/lambda ratio of 1.7 to 2 has been reported. However, little is known of the partition of light chains in secretions. The levels of IgA, kappa and lambda were assayed by nephelometry in a series of secretions and in normal human serum. Although kappa chains remained predominant, the different secretions studied could be classified according to their kappa/lambda ratio. In saliva (P < 0.001), nasal fluid (P = 0.01) and tears (P = 0.04) the kappa/lambda ratio was significantly lower than in serum. Conversely, higher kappa/lambda ratios were obtained in gastric juice (P = 0.005) and hepatic bile (P = 0.004) and no significant difference was noted between serum and gall bladder bile (P = 0.62). The lower ratios were all observed in fluids produced by glands surrounded by lymphoid tissue included in the mucosae-associated lymphoid tissue. These data strengthen previous observations that suggest a preferential production of lambda chains in human mucosae. PMID- 8004790 TI - Creatine kinase isoenzyme MB mass concentrations in patients undergoing aortocoronary bypass surgery. PMID- 8004791 TI - Tissue polypeptide specific antigen (TPS) in liver disease. PMID- 8004792 TI - The effect of silicon as silicic acid on superoxide dismutase activity. PMID- 8004793 TI - Concanavalin A affinity pattern of CA 19-9: an in vitro and in vivo study. PMID- 8004794 TI - Non-expression of von Hippel-Lindau phenotype in an obligate gene carrier. AB - Von Hippel-Lindau disease is generally considered to be a condition with very high penetrance, and individuals who live beyond the age of 60 years without showing any features of the disease, despite undoubtedly carrying the gene defect, have not previously been clearly described. The case is presented of a 65 year-old woman, who had four siblings affected with von Hippel-Lindau disease and had six children, three of whom died young with complications of von Hippel Lindau disease. Although she is an obligate gene carrier, she has not developed any significant manifestations of the disease despite careful screening for the neurological, retinal and renal complications. PMID- 8004795 TI - Roberts-SC phocomelia syndrome: a case with additional anomalies. AB - Roberts-SC phocomelia syndrome (RS) is an autosomal recessive disorder with symmetric limb defects, craniofacial abnormalities, pre- and postnatal growth retardation and mental retardation. Patients with RS were reported to have premature separation of heterochromatin of many chromosomes. We report an infant whose clinical, radiologic and chromosomal findings resemble those of RS, with rudimentary gallbladder and accessory spleen. This patient may represent a variant of RS. PMID- 8004796 TI - A new human mtDNA polymorphism: tRNA(Gln)/4336 (T-->C). AB - We report the observation of a polymorphism in the human mitochondrial tRNA(Gln) gene. This polymorphism is detectable by both NlaIII and Sau961, whose recognition sequences overlap at the polymorphic base pair. PMID- 8004797 TI - Autosomal dominant inheritance of thyroglossal duct cyst. PMID- 8004798 TI - Chromosome instability in lymphocytes from patients with celiac disease. AB - Cytogenetic studies were performed in celiac disease (CD) patients to determine if the presence of chromosome instability is related to the predisposition to cancer. Chromosome aberrations (CA) and sister chromatid exchange (SCE) frequencies in peripheral blood lymphocyte cultures from untreated CD patients and healthy controls were analyzed. Patients showed aberrations in 23% of cells, while only 3% were detected in the control group (p < 0.0001). The mean frequencies of gaps, breaks and total CA were found to be higher in CD patients compared to controls (p < 0.0001). Breakpoint distribution was nonrandom among chromosomes from celiac patients (p = 0.01), but not among controls (p = 0.04). The frequency of SCE/cell showed a mean value of 6.9 +/- 0.6 in CD patients and 7.3 +/- 0.2 in controls. No statistical differences were found. Breakpoints involved in CD patients presented a strong coincidence with the location of fragile sites (78.6%) and sites of cancer chromosome rearrangements (57.1%), most of them (75%) associated with malignant non-Hodgkin lymphomas. These results suggest that CD is a condition with increased chromosome instability characterized by a high level of CA and normal SCE frequencies, probably related to the increased incidence of cancer. PMID- 8004799 TI - Metaphase quality can be monitored by automatic counting of bands. AB - A high quality of cytogenetic preparations is important for maintaining a high standard in the cytogenetic laboratory. In the past, quality has been assessed by visual counting or estimation of the number of bands on chromosomes. In this paper we have counted bands automatically during karyotyping by using the Magiscan chromosome analysis system. A high correlation between automatic and visual counting was found, the automatic counting was reproducible and count figures were comparable when the karyotyping machines were operated by different technicians. The automatic counting procedure has now been included in our routine for 1 year. The highest numbers of bands were counted on slides from peripheral blood, with fewer bands for amniotic fluid and the lowest number for cells from chorionic villi. All three cell types showed significant variations in band number over time, which may be due to changes in weather conditions and/or the reagents used for cell culture, harvest and staining. It is concluded that the automatic counting procedure may be used to monitor the quality of metaphases over time and to set limits for band number on routine preparations acceptable for analysis. PMID- 8004800 TI - A fluorescent in situ hybridization analysis of the chromosome constitution of ejaculated sperm in a 47,XYY male. AB - Two semen samples from a 47,XXY male were examined using chromosome-specific DNA probes and fluorescent in situ hybridization (FISH) to determine the distribution of sex chromosomes and an autosome (chromosome 17) in the sperm. A motile population of sperm was also prepared from one sample using the swim-up technique to compare the motile and total sperm populations. Chromosomes were localized using single FISH and a biotinylated chromosome 17 probe (TR17), or double FISH using a biotinylated X chromosome probe (TRX) and a digoxigenin-labelled Y chromosome probe (HRY). Labelling efficiencies were 95-98%. Ploidy levels were estimated by measurement against a microscope eye-piece graticule. The overall ratio of X- to Y-bearing sperm was 47% to 48.4% in the neat samples, and 48.4% to 45.3% in the swim-up fraction. Neither of the ratios was significantly different from 1:1. The frequencies of monosomic and disomic (but otherwise haploid sperm) were not different from the frequencies we observed in normal donors. In contrast, the frequencies of both diploid and tetraploid cells were increased in the neat samples of the XYY male. In the swim-up fractions, however, none of these parameters differed from those of ten normal semen donors. These results support the hypothesis that the extra Y chromosome in XYY men is eliminated during spermatogenesis. PMID- 8004801 TI - Minimal genetic influences on plasma fibrinogen level in adult males in the NHLBI twin study. AB - Plasma fibrinogen was determined in 189 twins participating at the Indiana center during the third examination of the NHLBI twin study with a mean age of 63 years. Moderate heritability estimates were obtained from 44 complete MZ pairs and 39 complete DZ pairs. After adjustment of fibrinogen levels for age and other confounding variables related to cardiovascular disease risk, the maximum likelihood heritability estimate was only 30% (p = 0.03). Plasma fibrinogen was most strongly associated with smoking and the presence of diabetes. Omitting all subjects with diabetes or cardiovascular disease further reduced the heritability estimates slightly, and most path models including genetic parameters provided no significant improvement in fit over a model determined solely by random environmental effects. Our results are consistent with the environment rather than genetic influences having a greater influence on the level of plasma fibrinogen. PMID- 8004802 TI - Apolipoprotein B gene polymorphisms in ischemic heart disease and hypercholesterolemia: effects of age and sex. AB - The association of polymorphic alleles of the apolipoprotein B gene (Insertion/Deletion-, XbaI-, MspI-, EcoRI-, and 3'-VNTR polymorphisms) with variation in lipid concentrations (total cholesterol (T-C), HDL cholesterol (HDL C), and log-triglycerides (TG)) in plasma was studied in 259 men and 59 women with moderate hypercholesterolemia (T-C 5.5-8.0 mmol/l and TG < 2.5 mmol/l) and ischemic heart disease, especially in relation to the effect of sex and age. The XbaI and the Ins/Del polymorphic alleles were associated with variation in T-C, but only in patients below the 75th percentile for age. The XbaI and Ins/Del polymorphic alleles were synergistically associated with variation in T-C: the X+ and the Del alleles were associated with higher cholesterol concentrations. Younger male patients had the highest frequency of haplotypes including both the X+ and the Del alleles, but the most striking difference was a significantly higher frequency of haplotypes including both the X- and the Ins alleles in female and in older male patients. The heterogeneity of association of polymorphic alleles in the apolipoprotein B gene to complex traits like hypercholesterolemia and ischemic heart disease in this study could explain why in most studies the X+ allele has been associated with higher cholesterol levels, whereas the X- allele has been associated with symptomatic atherosclerosis. The results of our study emphasize the importance of age and sex in measured genotype association studies. PMID- 8004803 TI - An 87 bp deletion in exon 5 of the LDL receptor gene in a mother and her son with familial hypercholesterolemia. AB - DNA analysis of the low density lipoprotein receptor (LDLR) gene was performed in two persons with familial hypercholesterolemia (FH). Southern blot experiments indicated the heterozygous loss of an EcoRI site in exon 5 of the LDLR gene. Upon amplification and sequencing of exon 5 in both probands, an 87-bp deletion in a heterozygous state could be evaluated. This is a novel mutation, most probably leading to the formation of a nonfunctional LDLR. Analysis of the deletion breakpoints revealed the presence of a six-base-pair consensus sequence 5'TGA/GA/GG/TA/C3', which is characteristic of small deletions in different genetic defects. PMID- 8004804 TI - The gene for familial dystonia with myoclonic jerks responsive to alcohol is not located on the distal end of 9q. AB - A gene (DYT1) for susceptibility to early-onset torsion dystonia in Ashkenazi Jewish and Gentile kindreds is situated on chromosome 9q32-q34 in a 6-7 cM span between markers AK1 and ASS. To determine whether transmission of familial dystonia with myoclonic jerks responsive to alcohol was consistent with a gene in this region, we studied the 37 members of a Swedish family, of whom 20 were so affected. A lod score of < -2.00 from a two-point linkage analysis with six DNA markers covering a 30 cM span from D9S26 to D9S10 that included the region of the DYT gene indicated that this gene is not located in this region, and that two or more autosomal loci are responsible for hereditary dystonia in humans. PMID- 8004805 TI - A woman with an apparent non-mosaic 45,X delivered a 46,X,der(X) liveborn female. AB - A liveborn female with a phenotype suggestive of Down syndrome is reported. Cytogenetic lymphocyte analysis showed a 46,X der(X) karyotype. Fluorescence in situ hybridization (FISH) with a biotinylated probe specific for chromosome 21 showed no signal on the der(X). This marker was homogeneously painted using a specific probe for X chromosome. In addition, FISH analysis detected telomeres on the rearranged X. Therefore, the proband's karyotype was reevaluated as 46,X,del(X) (pter-->p22.2::p11.3-->qter). Cytogenetic analysis of 150 lymphocytes in the mother disclosed a homogeneous 45,X karyotype. FISH analysis of interphase nuclei using the X chromosome painting probe showed two domains of different sizes in 0.8% of cells. This led us to study further metaphases in the mother. In one out of 450 metaphases scored, after FISH with the X chromosome painting probe, the del(X) was observed, confirming that the rearranged X chromosome found in the newborn had segregated from a 45,X/46,X,del(X) mother. PMID- 8004806 TI - Duchenne muscular dystrophy and spinal muscular atrophy type I segregating in the same family. AB - We report on a family with two severe neuromuscular diseases: Duchenne muscular dystrophy (DMD) and acute infantile spinal muscular atrophy (SMA I). One boy has DMD, and his brother died of SMA I at 11 months of age. Both boys had received the same DMD allele from their mother. Analysis of dystrophin by immunohistochemistry and Western blot showed complete lack of dystrophin in both brothers. The mother had a partial deficiency of dystrophin. The boy with SMA I had increased levels of creatine kinase in serum, compatible with DMD, but the muscle biopsy and post-mortem examination of the spinal cord showed the typical changes of SMA I. There were no cytogenetic abnormalities explaining the occurrence of both DMD and SMA I in this family. Molecular genetic prenatal diagnosis of DMD and SMA I, using analysis of RFLPs and dinucleotide repeats, has been performed in one foetus in the family. The results showed that the foetus had a high risk of developing SMA I. An abortion was planned but the pregnancy was terminated by miscarriage. PMID- 8004807 TI - Mucosal immunology research design should address not just cytokines and cells, but also clinical data and controls. PMID- 8004808 TI - Antibody-dependent enhancement of HIV-1 infection in human term syncytiotrophoblast cells cultured in vitro. AB - We examined if Fc receptor-mediated antibody-dependent enhancement (FcR-ADE) or complement-mediated antibody-dependent enhancement (C'-ADE) of virus infection can contribute to increasing replication of HIV-1 in human syncytiotrophoblast (ST) cells. Here we report that both FcR-ADE and C'-ADE may result in enhanced virus release from HIV-1-infected ST cells. We show that FcR-ADE of HIV-1 infection in ST cells is mediated by FcRIII and other FcR(s) belonging to undetermined Fc classes and does not require CD4 receptors, whereas C'-ADE uses both CD4 and CR2-like receptors. FcR-ADE seems to be more efficient in enhancing HIV-1 replication than C'-ADE. While FcR-ADE leads to increased internalization of HIV-1, C'-ADE does not result in enhanced endocytosis of the virus. In addition, antibodies mediating FcR-ADE are reactive with the gp120 viral envelope antigen, whereas antibodies involved in C'-ADE react with the viral transmembrane glycoprotein gp41. Data suggest that both FcR-ADE and C'-ADE may contribute to the spread of HIV-1 from mother to the fetus. PMID- 8004809 TI - Dichotomy of the human T cell response to Leishmania antigens. I. Th1-like response to Leishmania major promastigote antigens in individuals recovered from cutaneous leishmaniasis. AB - The T cell response to antigens from Leishmania major promastigotes was investigated in peripheral blood mononuclear cells from Sudanese individuals with a history of cutaneous leishmaniasis (CL), Sudanese individuals with positive DTH reaction in the leishmanin skin test but with no history of skin lesions, and in Danes without known exposure to Leishmania parasites. Proliferation and production of interferon-gamma (IFN-gamma) and IL-4 in antigen-stimulated cultures was measured. Lymphocytes from individuals with a history of CL proliferated vigorously and produced IFN-gamma after stimulation with either a crude preparation of L. major antigens or the major surface protease gp63. These cultures produced no or only little IL-4. Also cells from leishmanin skin test positive donors with no history of CL produced IFN-gamma and no IL-4 in response to L. major antigens. Cells from the unexposed Danes were not activated by gp63. The cells from Danish donors produced either IFN-gamma or IL-4, but not both cytokines after incubation with the crude preparation of L. major antigens. The data show that the T cell response to Leishmania antigens in humans who have had uncomplicated CL or subclinical L. major infection is an IFN-gamma-producing Th1 like response. PMID- 8004810 TI - Dichotomy of the human T cell response to Leishmania antigens. II. Absent or Th2 like response to gp63 and Th1-like response to lipophosphoglycan-associated protein in cells from cured visceral leishmaniasis patients. AB - The T cell response to different Leishmania donovani antigens was investigated using peripheral blood mononuclear cells (PBMC) from Kenyans cured of visceral leishmaniasis and non-exposed Danes. Crude promastigote and amastigote antigens both induced proliferation and interferon-gamma (IFN-gamma) production in PBMC from cured patients, while cells from non-exposed donors gave weak responses. A similar pattern was induced by lipophosphoglycan-associated protein (LPGAP). By contrast, the major surface protease of Leishmania, gp63, induced only a weak proliferative response without IFN-gamma production in five of 17 samples from cured patients. Four of the five responding cultures produced IL-4, i.e. the response to this antigen was of the Th2 type. Furthermore, sera from acutely ill visceral leishmaniasis patients contained high levels of IgG antibodies to gp63. The Th2-like response to gp63 in patients cured of visceral leishmaniasis differs from the Th1-like response to the same antigen observed in patients cured of cutaneous leishmaniasis. PMID- 8004812 TI - IL-8 as an important chemoattractant for neutrophils in ulcerative colitis and Crohn's disease. AB - IL-8 is generating increasing interest as a powerful neutrophil chemoattractant and activator. To elucidate the mechanisms of neutrophil infiltration in inflammatory bowel disease, we examined 33 patients with ulcerative colitis (UC), 18 with Crohn's disease (CD), eight with some other type of colitis, and 18 normal control subjects for measurement of IL-8 in homogenates of colonic biopsy specimens. The affected colonic mucosa was found to contain significantly more IL 8 in patients with active inflammatory bowel disease than in patients with inactive disease (UC, P < 0.001; CD, P < 0.001), in patients with other types of colitis (UC, P < 0.05; CD, P < 0.01), or in normal control subjects (UC, P < 0.001; CD, P < 0.001). Colonic IL-8 levels correlated significantly with the macroscopic grade of local inflammation, especially in patients with UC (P < 0.001). Colonic IL-8 levels also correlated well with the neutrophil numbers in mucosal tissue (UC, r = 0.950, P < 0.001; CD, r = 0.940, P < 0.001), and with colonic IL-1 beta (r = 0.911, P < 0.001) and tumour necrosis factor-alpha (TNF alpha) levels (r = 0.604, P < 0.001) in patients with these two conditions. These data suggest a potential role for IL-8 and its regulatory cytokines IL-1 and TNF alpha in mediating neutrophil infiltration of the gut wall in inflammatory bowel disease. PMID- 8004811 TI - The significance of anti-streptokinase antibodies. AB - Antibodies to streptokinase (SK) are widespread in the population, but reports of their effect on the action of SK are conflicting. Specific anti-SK IgG was purified from the sera of 10 patients, five with low titres of anti-SK IgG and five with high titres. The effect of increasing specific anti-SK IgG antibodies on the action of SK was evaluated in vitro using a fluorimetric assay for plasmin and by a fibrin plate lysis assay. The inhibition of SK by whole plasma from a further group of patients was also assessed by the fibrin plate assay. There was a positive correlation between the serum antibody concentration and the quantity of specific anti-SK eluted (r = 0.797; P < 0.005). The addition of specific anti SK IgG caused a dose-related decrease in SK activity (fluorimetric assay r = 0.93; P = 0.02; fibrin plate assay r = -0.98; P < 0.001). The addition of patient plasma to the fibrin plate assay also resulted in decreased lysis, which was dependent upon antibody titre (r = -0.95; P < 0.0001). Significant in vitro reduction of the activity of SK by specific antibody was demonstrated, and this was similar with plasma containing comparable amounts of antibody. The findings suggest that treatment with SK would be unlikely to induce an effective thrombolytic state when antibody titres are high (such as those seen within 2 years of an initial dose of SK). PMID- 8004813 TI - GM-CSF, IL-1 alpha, IL-1 beta, IL-6, IL-8, IL-10, ICAM-1 and VCAM-1 gene expression and cytokine production in human duodenal fibroblasts stimulated with lipopolysaccharide, IL-1 alpha and TNF-alpha. AB - The role of mucosal fibroblasts in intestinal inflammatory reactions is not known. In this study, we demonstrate that fibroblasts grown from histologically normal human duodenal biopsy tissues expressed mRNA genes for granulocyte macrophage colony-stimulating factor (GM-CSF), IL-1 alpha, IL-1 beta, IL-6, IL-8, IL-10, intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) when stimulated with lipopolysaccharide (LPS) or IL-1 alpha. The increased mRNA expression of GM-CSF, IL-1 alpha, IL-1 beta, IL-6 and IL-8 in response to IL-1 alpha and LPS stimulation was time- and dose-dependent. In contrast, IL-10 was weakly expressed when fibroblasts were stimulated with LPS, IL-1 alpha or tumour necrosis factor-alpha (TNF-alpha), but the expression was enhanced in the presence of cycloheximide combined with optimal concentrations of LPS, IL-1 alpha or TNF-alpha, IL-1 alpha was a more potent stimulator than LPS for GM-CSF, IL-6, IL-8 and IL-10 expression, but not for IL-1 alpha and IL-1 beta. Increased GM-CSF, IL-6 and IL-8 gene expression was associated with the production of cytokine proteins in culture supernatant, but IL-1 alpha and IL-1 beta remained undetectable. Dexamethasone suppressed both gene expression and protein production of GM-CSF, IL-6 and IL-8 when fibroblasts were exposed to IL-1 alpha. TNF-alpha stimulated the release of GM-CSF, IL-6 and IL-8 and, combined with IL-1 alpha, cytokine production was enhanced synergistically. Finally, both LPS and IL-1 alpha up-regulated ICAM-1 and VCAM-1 gene expression. These findings implicate duodenal fibroblasts in the initiation and/or regulation of intestinal inflammation. PMID- 8004814 TI - Anti-endothelial cell antibodies in sera of patients with autoimmune diseases: comparison between ELISA and FACS analysis. AB - In some patients suffering from rheumatoid arthritis (RA), vasculitis is a clear clinical manifestation, mentioned as rheumatoid vasculitis (RV). Autoantibodies directed against endothelial cells (AEA) have been implicated in the pathogenesis of this disorder, and it has been suggested in a number of studies that testing for AEA should be included in diagnosing RV. To test this hypothesis, we have evaluated the presence of AEA in sera of patients suffering from various autoimmune diseases, employing an ELISA with fixed cultured endothelial cells (EC). In all the groups of patients ELISA-positive sera were present. A significant difference in percentage of positivity was found between the RA and RV group (P < 0.05). In addition, our results indicated that not only antibodies directed against antigens on the EC membrane were detected, but also antibodies directed against intracellular components like DNA, histones and cytoskeletal components. Therefore, we also tested all these patient sera on unfixed intact EC using indirect immunofluorescence followed by FACS analysis. Whereas in the total patient population 34 out of 65 patients were AEA-positive as determined in the ELISA, only seven patients were weakly positive when examined by flow cytometry. We conclude that: (i) an ELISA on fixed EC does not specifically detect AEA. A positive test result is, however, to some extent correlated with the occurrence of vasculitis, and may therefore be helpful in diagnosing this disease; (ii) FACS analysis is a more suitable method than ELISA to measure the presence of membrane specific AEA in patient sera; (iii) specific IgG-AEA are less common in patients suffering from autoimmune disorders than was assumed previously. PMID- 8004816 TI - Monoclonal IgM from patients with peripheral demyelinating neuropathies cross react with bacterial polypeptides. AB - Human monoclonal IgM associated with a demyelinating peripheral neuropathy often feature a distinct antibody activity directed against a glucuronyl sulphate epitope shared by myelin-associated glycoprotein (MAG), nerve glycolipids and low molecular weight peripheral nerve polypeptides. Earlier studies showed that these IgM use a diverse repertoire of VH and VL genes which exhibit somatic mutations, possibly indicative of an antigen-driven process. Here, we investigated whether such monoclonal IgM may react with environmental bacterial antigens. We found that six patients' sera and purified monoclonal IgM, as well as IgM from supernatants of three clonal anti-MAG-secreting cell lines reacted with unique 90 100 kD polypeptides from extracts of two out of 10 bacterial species. Purified MAG was able to inhibit this reactivity. These results indicate molecular mimicry as a possible mechanism of this immunomediated neuropathy and associated clonal lymphoid disease. PMID- 8004815 TI - Precursor frequencies for DNA-specific B lymphocytes in patients with systemic lupus erythematosus (SLE). AB - Precursor frequencies for anti-DNA-secreting B cells were estimated in six healthy donors and 18 SLE patients with active and inactive disease. Precursors for IgG anti-dsDNA-secreting B cells were exclusively detected in SLE patients (73% of active patients and one inactive patient, 0.01-0.99% of IgG-producing B cells). These frequencies were in the same order of magnitude as frequencies of precursors for IgG anti-tetanus toxoid, which were detectable in three healthy volunteers after booster vaccination (0.07-0.8% of IgG-producing B cells), but not before (< 0.01%). Precursors for IgG anti-ss-DNA secreting B cells were observed in 33% of healthy donors and in 78% of SLE patients (0.01-0.32% of IgG producing B cells). Only patient-derived IgG anti-DNA clones cross-reacted with (33%) or were monoreactive to dsDNA (12%). Precursors for IgM anti-DNA-secreting B cells were observed in healthy donors and SLE patients in comparable frequencies and with similar reactivities with ssDNA and dsDNA. Segregation analyses and sorting experiments showed that > 94% of clones secreting IgG anti DNA were derived from in vivo sIgG+ B cells. sIgM+ B cells were induced to switch in vitro; however, only twice were cultures containing IgM and IgG anti-DNA antibodies observed under clonal conditions. In conclusion, our results indicate that precursor B cells for IgG anti-dsDNA in SLE patients are similarly selected and expanded as are precursor B cells specific for foreign antigens such as tetanus toxoid. PMID- 8004817 TI - Anti-alpha beta T cell receptor antibody prevents the progression of experimental autoimmune myocarditis. AB - We investigated the effects of anti-alpha beta T cell receptor antibody in rat experimental autoimmune myocarditis (EAM), using a new animal model of autoimmune myocarditis characterized by the appearance of multinucleated giant cells. EAM was induced by injecting Lewis rats subcutaneously in the footpads with 1.0 mg of human cardiac myosin in an equal volume of Freund's complete adjuvant (FCA) on days 0 and 7. In experiment 1, we evaluated the effect of long-term anti-alpha beta TCR antibody therapy on prevention of progression of EAM. Long-term administration of anti-alpha beta TCR antibody prevented progression of EAM in a dose-dependent manner. Flow cytometry performed at the time of sacrifice showed that the percentage of alpha beta T cells in lymph nodes and spleen was similar in the control group and the group in which almost no histologic evidence of myocarditis was found. In experiment 2, we examined the effects of short-term therapy. Rats were killed at different stages and pathologic specimens were examined. Short-term therapy delayed the onset of myocarditis. Results of flow cytometry suggested that impairment of antigen recognition or T cell function by occupancy of the TCR rather than depletion of TCR was the mechanism responsible for suppression of EAM. PMID- 8004819 TI - Lymphokine-activated killer cell function of peripheral blood mononuclear cells, spleen cells and regional lymph node cells in gastric cancer patients. AB - Lymphokine-activated killer (LAK) cells generated by culture of peripheral blood mononuclear cells (PBMC), spleen cells (SPC) and regional lymph node cells (LNC) with IL-2 for 4 days were examined for their functional capabilities in 29 patients with gastric carcinoma. The cytotoxic activity of LAK cells induced from LNC was significantly lower than that from either PBMC or SPC, although there was no difference between PBMC or SPC. The induction of mRNA of interferon-gamma (IFN gamma) or tumour necrosis factor-alpha (TNF-alpha) and the production of these cytokines in the non-adherent LAK cells from LNC were also significantly reduced compared with those from PBMC or SPC. Further, the LAK cells from LNC secreted significantly lower levels of these cytokines when stimulated with tumour target, Raji cells, although the production of these cytokines was markedly increased by stimulation with the targets in all three cell populations. Phenotypic analysis of each cell population revealed a decreased proportion of the cells mediating natural killer (NK) activity, including CD16+, CD56+, and CD57+ cells in LNC either before or after culture, although OKIa1+ and CD25+ cells were uniformly increased in all cell populations after culture. Changes in subpopulations of CD4+ and CD8+ cells in LNC were not apparently different from PBMC or SPC. These results indicated the differential reactivity of each lymphocyte population to IL 2 and the reduced LAK cell function of LNC compared with PBMC or SPC in patients with gastric carcinoma. PMID- 8004820 TI - Attenuation of lpr-graft-versus-host disease (GVHD) in MRL/lpr spleen cell injected SCID mice by in vivo treatment with anti-V beta 8.1,2 monoclonal antibody. AB - When MRL/lpr (H-2k) spleen cells were intraperitoneally injected into C.B-17 scid/scid (severe combined immunodeficient (SCID)) (H-2d) mice, the SCID (SCID MRL/lpr) mice manifested a severe wasting syndrome with weight loss, splenic atrophy, and lymphoid cell infiltration in the liver and lung, as seen in lpr GVHD. In contrast, MRL/+ spleen cell-injected SCID (SCID-MRL/+) mice did not show lpr-GVHD. The spleens of SCID-MRL/lpr mice showed progressive increases in donor CD4+ and CD8+ T cells from 4 to 12 weeks after injection and a decrease in B cells at 12 weeks. SCID-MRL/+ mice showed a stable engraftment of CD4+ and CD8+ T cells and a progressive increase in B cells. Analyses of T cell receptor (TCR) repertoires (V beta 6, V beta 8.1,2 and V beta 11) revealed that the V beta 8.1,2+ T cells were found more frequently in SCID-MRL/lpr mice than in SCID-MRL/+ mice. When SCID-MRL/lpr mice were treated with intraperitoneal injection of an anti-V beta 8.1,2 (KJ16) MoAb, V beta 8.1,2+ T cells were markedly depleted, and the severity of lpr-GVHD was attenuated at 4 and 8 weeks after treatment, in contrast to normal rat IgG-injected SCID-MRL/lpr mice. However, the KJ16 MoAb treated SCID-MRL/lpr mice suffered from severe lpr-GVHD 12 weeks after treatment, although V beta 8.1,2+ T cells were still maintained at a low level. These findings suggest that V beta 8.1,2+ T cells are a major T cell population that mediates lpr-GVHD in the early stage of lpr-GVHD, but that in the later stage, the other T cell populations may proliferate naturally or in accordance with the depletion of V beta 8.1,2+ T cells, and contribute to the development of lpr GVHD. PMID- 8004821 TI - Effects of cyclosporine and rapamycin on immunoglobulin production by preactivated human B cells. AB - In order to assess the direct effects of cyclosporine A (CsA) and rapamycin on B cells, we utilized a two-segment culture system of highly purified B lymphocytes consisting of induction (activation) in the presence of the formalinized Staphylococcus aureus bacteria and IL-2, and differentiation, respectively, in the presence of various combinations of cytokines. Results show that rapamycin strongly inhibited production of both IgM and IgG measured at the end of the secondary culture supported by IL-2/IL-6, whereas CsA up-regulated the immunoglobulin production. The stimulatory effect of CsA was also observed when preactivated B cells were recultured in absence of any cytokines. These results show that rapamycin and CsA have clearly distinct effects on human B lymphocyte responses in vitro. Rapamycin is a more potent in vitro immunosuppressant of B lymphocytes than CsA. It is effective at significantly lower concentrations, and it does not stimulate either the proliferation or antibody production by preactivated B cells. PMID- 8004818 TI - Growth and major histocompatibility antigen expression regulation by IL-4, interferon-gamma (IFN-gamma) and tumour necrosis factor-alpha (TNF-alpha) on human renal cell carcinoma. AB - We have recently shown that human renal cell carcinoma (RCC) tumour lines express high-affinity IL-4 receptors. Binding of IL-4 to RCC cells induced a growth inhibition in the range of 20-68%. To enhance the growth inhibitory effect of IL 4, we have tested the effects of two additional cytokines capable of directly affecting tumour cell growth. IFN-gamma caused a significant inhibition of RCC tumour cell growth (up to 70%) in a dose-dependent manner, whereas the effect of TNF-alpha was more limited (0-20% inhibition). The addition of IL-4 to IFN-gamma on RCC cells sensitive to IL-4 induced a greater inhibition of cell growth than that seen with each cytokine alone. IL-4 and IFN-gamma rendered RCC cells more responsive to the inhibitory effect mediated by TNF-alpha. The combination of TNF alpha with IL-4 and IFN-gamma induced an optimal growth inhibition (up to 90-98%) of RCC cells. In addition to a direct anti-proliferative effect, we have demonstrated that these cytokines can also enhance the expression of MHC antigens on the surface of RCC tumour cell lines which may render the cells more immunogenic. All RCC lines tested expressed class I antigens, but not class II antigens. IFN-gamma induced class II expression and up-regulated the expression of class I antigens on RCC cells. Class II antigen expression was detectable following 48 h incubation, and greater after 72 h with IFN-gamma. IL-4 minimally affected class I expression, whereas TNF-alpha up-regulated class I antigen expression. IL-4 or TNF-alpha did not induce class II expression. The combination of the three cytokines slightly augmented the up-regulation of class I and class II antigens observed with IFN-gamma alone. These observations confirm the direct interaction of IL-4, IFN-gamma and TNF-alpha with RCC tumour cells, both at the level of growth regulation and MHC antigen expression, and suggest a therapeutic potential of the combination of the three cytokines for renal cell carcinoma. PMID- 8004824 TI - A challenge to nursing education: meeting the health care needs of the Hispanic community. PMID- 8004823 TI - Augmentation of antigen-specific lymphoproliferative responses in vitro by biological response modifiers. AB - The detection of antigen-specific T cell responsiveness, particularly of resting memory lymphocytes, in cultures of peripheral blood mononuclear cells (PBMC) may be hampered by a less than optimal antigen presentation in vitro. Augmented sensitivity of the test system may be achieved by the addition of reagents with a beneficial effect on lymphocyte and antigen-presenting cell (APC) functions. In this study the effect of several biological response modifiers on antigen specific T cell proliferation was determined, using nickel sulphate and tetanus toxoid as test antigens. IL-1 alpha (100 U/ml), interferon-gamma (IFN-gamma) (10 U/ml), and indomethacin (2 microM) were found to significantly enhance nickel induced proliferation in PBMC cultures from nickel-hypersensitive donors (n = 6). Tetanus-induced proliferation (n = 5) was similarly enhanced, both by the above supplements and by the addition of polyethylene glycol (PEG) or a neuraminidase treatment of the PBMC before culture. The addition to PBMC cultures of a combination of IL-1 alpha (30 U/ml), IFN-gamma (10 U/ml), and indomethacin (2 microM) is recommended to specifically enhance antigen-induced lymphoproliferative signals. PMID- 8004822 TI - The effects of in vivo cyclosporin A administration on rat thymic dendritic cells. AB - Cyclosporin A (CsA) induces a graft-versus-host-like disease (GVHD) in lethally irradiated Lewis rats reconstituted with syngeneic bone marrow. The role of the thymus in the generation of disease has been unequivocally established. It has been suggested that the CsA-induced disappearance of thymic dendritic cells (DC) is responsible for the generation of the autoaggressive cells. In this study we quantify the loss of DC upon in vivo CsA administration in normal and bone marrow reconstituted rats using an isolation technique. The phenotype of the DC is determined using MoAbs recognizing antigens which are expressed on thymic medullary DC. Furthermore, the functional aspects are assessed by determining the antigen presentation capacity. Short-term CsA exposure clearly affects the number of DC isolated from the thymus in a concentration-dependent manner. However, in all instances a substantial number of DC can be isolated from CsA-treated animals. These isolated DC exhibit an identical phenotype and function as DC isolated from control animals. Therefore, the partial deficiency of DC can not be held as essential for loss of tolerance. PMID- 8004825 TI - The risk of ano-genital malignancies in dialysis and transplant patients. AB - The incidence of anogenital malignancies is greatly increased in patients who have received a renal transplant, but this has not been well studied in patients receiving maintenance dialysis. Our aim was to assess the incidence of these malignancies in patients on dialysis and compare these to transplanted patients. The age standardized incidence ratio (SIR) for anogenital malignancies was calculated by comparing the observed number of malignancies to the expected number. The expected number was calculated by multiplying the age specific incidence rates for each malignancy by the person years at risk in 5-year age cohorts. Of 15,820 patients in the Australia and New Zealand data base, 8,215 had received a renal transplant. A total of 39,750 person years at risk were contributed by patients who had received a renal transplant, while 29,276 person years at risk were contributed by dialysis patients who had not received a renal transplant. For dialysis patients, vulval cancer occurred more commonly than expected (2 observed, 0.48 expected) giving a SIR of 4.2 (95% confidence interval = 0.4-11.9). Cervical cancer occurred less commonly with a SIR of 0.74 (95% Cl = 0.07-2.11). No cases of either anal or penile cancer occurred although these are rare tumors, with only 0.13 and 0.23 cases expected respectively. In transplant recipients 44 anogenital malignancies occurred while 4.3 could have been expected. The SIR ranged from 3.3 (95% Cl 1.7-5.8) for cervical cancer to 55.8 (95% Cl 35.8-83.0) for vulval cancer. To investigate the possible effect of chronic uremia before dialysis began, SIR was calculated to include an additional 24 months of observation before dialysis.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8004826 TI - Changes in plasma levels of vasoactive substances during routine acetate and bicarbonate hemodialysis. AB - Hemodynamic stability is better preserved during bicarbonate hemodialysis compared to acetate. We have studied the effects of bicarbonate (HDB) and acetate hemodialysis (HDA) on plasma levels of vasoactive substances. The treatments were performed for 270 min. A cuprophan plate dialyzer was used. The ultrafiltration volume and the ultrafiltration rate were identical in the individual patients during the two treatments. In the case of vasoconstrictors there was an increase in neuropeptide Y (NPY) (20%, p < 0.01) during HDB and arginine vasopressin (AVP) was unchanged. Unlike this was the response during HDA when there was no change in NPY and a decrease in AVP (38%, p < 0.01). An increase in noradrenaline (NA) (41%, p < 0.05) occurred during HDA different from what was the case during HDB. There was a gradual increase in renin (PRA) during both HDB (141%, p < 0.05) and HDA (148%, p < 0.01). With respect to vasodilators there were no differences between the two regimes regarding calcitonin gene-related peptide (CGRP) and motilin (MOT). The change in substance P (SP) during the treatments was also similar but somewhat more pronounced during HDB. Thus, an initial rise occurred (HDB, 81%, p < 0.01; HDA, 36%, p < 0.05) followed by a decrease (HDB, 26%, p < 0.05) or a tendency to decrease (HDA, 12%, p = 0.058) during the remaining part of the treatment. A rise in beta-endorphin (beta-END) occurred during HDB (10%, p < 0.05) but not during HDA. An increase in vasoactive intestinal peptide (VIP) occurred during HDB (27%, p < 0.05) different from the decrease during HDA (11%, p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8004827 TI - Hepatitis C virus infection decreases the effective antibody response to hepatitis B vaccine in hemodialysis patients. AB - Hepatitis B remains a significant risk to patients receiving chronic hemodialysis. Hepatitis B vaccines are effective in providing protection against this infection. However, the minimum antibody level necessary to guarantee an efficacious protection is not clear. Little is known about the effect of this vaccine in persons treated with erythropoietin (EPO) and in patients with hepatitis C virus (HCV) infection. We have studied 36 chronic hemodialysis patients; 17 of them receiving EPO and 9 were diagnosed as having HCV infection. Effective immunity (antibody titer higher than 100 mIU/ml) was observed in 61.1% of the participants and was not influenced by EPO administration, but the effective immunization rate was lower in HCV infected patients (33.3% vs. 70.3%, p < 0.05). These results suggest the possibility that HCV infection may modify the effectiveness of hepatitis B vaccine. PMID- 8004829 TI - Influence of recombinant human erythropoietin on growth hormone responses to growth hormone releasing hormone in uremic patients. PMID- 8004828 TI - IgA nephropathy demonstrating clinico-serologic features of acute post streptococcal glomerulonephritis. PMID- 8004830 TI - The influence of pregnancy on the long-term renal prognosis of IgA nephropathy. AB - The effect of pregnancy on long-term renal prognosis in women with IgA nephropathy is disputed. The clinical courses of 71 patients with biopsy proven IgA nephropathy were followed for 5 years. Thirty-six patients became pregnant during the first 2 years of follow-up (P), the remaining 35 never conceived (non P). The pathology in preconception renal biopsy was similar to that of the women who never became pregnant. Glomerular filtration rate (GFR) was measured yearly as the 24 hour-clearance of creatinine and was compared between the two groups. Initial clinical data of the P and non-P were: average age 25 +/- 3: 25 +/- 3 (yrs); serum creatinine 0.8 +/- 0.2: 0.7 +/- 0.2 (mg/dl); GFR 83 +/- 15: 87 +/- 15 (ml/min); blood pressure 119 +/- 10/74 +/- 9: 121 +/- 17/71 +/- 8 (mmHg); proteinuria 0.6 +/- 0.4: 0.9 +/- 0.6 (g/day). There were no significant differences between the two groups. Average initial (83 +/- 15: 87 +/- 15) and final (69 +/- 28: 69 +/- 24) GFRs were comparable. In 80% of P and 74% of non-P patients, the GFR decrement was 25% or less at five years. Four of the P and two of the non-P progressed to end-stage renal failure and required hemodialysis. No adverse influence of gestation on the natural course of IgA nephropathy was detected. PMID- 8004832 TI - The immunolocalization and urinary quantitation of 7-5Q/A, a unique human renal antigen. AB - In this communication 7-5Q/A, a recently described human kidney-specific acidic membrane glycoprotein, was immunolocalized by immunofluorescence in kidney and placenta, and by immunogold electron microscopy in the kidney. The antigen is located above and below the slit diaphragm on epithelial cell foot processes in the glomerulus, and also on proximal tubular brush border membranes. In the placenta it was present on epithelial membranes. 7-5Q/A and dipeptidylpeptidase IV were compared by a variety of techniques because of their similar size and possible location, and found to be distinct. A sensitive sandwich ELISA was developed using polyclonal and monoclonal antibodies to 7-5Q/A, and applied to the quantitation of this antigen in the urines and sera of patients with a variety of kidney diseases, and in the urines and sera of normal subjects. The concentration of 7-5Q/A in normal urines ranged from 0 to 2 ng/ml but levels of up to 150 ng/ml were found in urines of patients with renal disease. 7-5Q/A was not detectable in either normal or nephritic sera. Urinary quantitation of this unique antigen may be of value in the early diagnosis of renal disease. PMID- 8004831 TI - Clinical and histopathologic associations with impaired renal function in IgA nephropathy. Mayo Nephrology Collaborative Group. AB - A multicenter, double-blind, placebo-controlled, randomized trial of fish oil in proteinuric patients with IgA nephropathy is being conducted by the Mayo Nephrology Collaborative Group. We completed enrollment of 106 patients into the trial in December 1991. The treatment period is for two years. Hypertension is being managed in all patients with enalapril maleate (Vasotec). We evaluated the associations between a variety of clinical and renal morphologic features and renal function at the entry of all enrolled patients. Among 78 males and 28 females [age(mean +/- SD) 36 +/- 14 years], older age at treatment randomization, hypertension, at disease discovery as well as at study entry, increased fractional excretion of albumin, increased serum triglyceride levels, and more severe tubulointerstitial, vascular, and combined glomerular and tubulointerstitial histologic lesions were all univariately associated (p < or = 0.01) with poorer renal function measured by reciprocal serum creatinine and creatinine clearance levels. In a multiple regression analysis used to predict baseline reciprocal creatinine, the best final model (R2 = 0.48) included male sex (p < .001), hypertension at treatment randomization (p = .001), decreased peripheral blood erythrocytes (p = .001), increased tubulointerstitial score (p = .004), and increased fractional excretion of albumin (p = .025) as independent predictors of decreased kidney function. These associations are similar to those seen in the high-risk subset of patients with IgA nephropathy who develop end stage renal disease. In the eventual outcome analysis of the clinical trial, we will examine the effects of treatment on the two potentially modifiable risk factors, hypertension and proteinuria, on renal function. PMID- 8004833 TI - Chronic occult intra-alveolar hemorrhage: a rare cause of failure to respond to erythropoietin. AB - Recombinant human erythropoietin (EPO) is an effective and safe therapy for correction of anemia in end-stage renal disease (ESRD). Clinical trials reported to date suggest that EPO improves anemia in over 90% of hemodialysis patients with anemia (Eschbach 1989). Factors which have been identified that appear to inhibit the effectiveness of EPO are infection [Muirhead N et al. 1990], iron deficiency, hyperparathyroidism, aluminium excess [Casati 1991] and persistent GIT bleeding. The development of reticulocytosis in response to EPO in the absence of a rise in hematocrit should alert the clinician to the possibility of either hemolysis or occult blood loss. We present a case in which, despite the development of a reticulocytosis of 5% in response to EPO and the absence of hemolysis, we had difficulty in identifying the presumed source of blood loss. PMID- 8004834 TI - Pattern of endothelin immunostaining during rejection episodes after kidney transplantation. AB - A pathophysiological role for endothelin (ET), one of the most potent vasoconstrictor peptides, has been suggested in ATN and during kidney allograft rejection. As ET is known to have predominantly local effects, we investigated intrarenal ET content in 82 kidney transplant biopsies and 10 normal control kidneys. ET-immunostaining, using a polyclonal anti-ET-1 antibody was investigated in 4 intrarenal vascular beds (glomeruli, capillaries, arterioles, arteries) and in tubular epithelium. Normal kidneys showed a strong staining of endothelial cells in all vessels and of tubular epithelium. In biopsies with signs for acute vascular rejection a marked decrease in ET staining intensity was seen. In contrast, normal staining similar to control kidneys was detected in interstitial rejection and in ATN. The presence of chronic CyA toxicity, however, lead to a significant reduction of endothelial ET staining. Neither mean doses nor trough levels of CyA correlated closely with the immunostaining findings. Plasma big-ET levels were elevated during vascular rejection, but not in interstitial rejection and ATN. This study demonstrates a significant reduction of ET immunostaining in intrarenal vascular endothelium of kidney transplant biopsies showing signs of endothelial damage. In vascular allograft rejection these changes are often associated with a concomitant rise in plasma ET levels. Our findings support a postulated role of ET in vascular rejection and during CyA toxicity and show that endothelial damage, independent of its genesis, can lead to a reduction of intrarenal ET content. PMID- 8004835 TI - Nitric oxide as a therapeutic agent. AB - The vasorelaxant property of inhaled nitric oxide is rapidly lost because it binds to hemoglobin. Its selective action in the pulmonary circulation and bronchial smooth muscle has the advantage of not decreasing systemic vascular resistance with resultant systemic hypotension. In the adult population, patients with ARDS, COLD, asthma, and increased pulmonary vascular resistance postoperatively are likely to benefit from inhaled nitric oxide, at least transiently. However, before inhaled nitric oxide can be recommended for routine use, further study of the potential adverse effects needs to be carried out. PMID- 8004836 TI - Unstable angina: prognosis, noninvasive risk assessment, and strategies for management. AB - Risk stratification in patients with unstable angina is a major clinical problem with important therapeutic implications. Antiplatelet therapy is clearly effective in reducing the occurrence of myocardial infarction and death in this syndrome. Interventions including coronary bypass surgery and coronary angioplasty are frequently recommended for these patients, but the most appropriate application of these techniques needs to be further defined. After a brief discussion of the value of medical and interventional therapies, this review focuses on the clinical and noninvasive predictors of adverse events in unstable angina. An overall management strategy for these patients, based on current information, will be proposed. PMID- 8004837 TI - Noninvasive localization of accessory pathways by magnetocardiographic imaging. AB - The magnetocardiogram (MCG) is a newly developed method that helps localize a cardiac current source. To test the clinical accuracy of a 7-channel biomagnetic system in the localization of early ventricular depolarization sites, the MCGs of 14 patients with Wolff-Parkinson-White (WPW) syndrome were recorded in a radiofrequency-shielded room. The locations of early ventricular depolarization sites were classified by standard 12-lead electrocardiograms (ECGs) and body surface isopotential mapping. The accessory pathways of 3 patients with WPW syndrome were located in the right free wall and in 11 patients in the left free wall. The three-dimensional (3-D) dipole location was computed every 2 ms from the onset of the QRS complex by the least-square method. These 3-D dipole locations were projected onto a gated magnetic resonance image in order to visualize the propagation of the calculated ventricular source. The results were compared with those obtained by body surface isopotential mapping, and electrocardiographic and electrophysiologic studies. The location of the deduced current dipole at 20 ms correlated well with the location of the accessory pathway by the body surface mappings in 12 of the 14 patients with WPW syndrome. The MCG is capable of precisely determining the 3-D location of a current source in a noninvasive manner and may be of potential benefit in the treatment of WPW syndrome by catheter ablation. PMID- 8004838 TI - Efficacy of rapid atrial pacing for conversion of atrial flutter in medically treated patients. AB - To determine factors affecting the success rate of rapid atrial pacing in converting atrial flutter to sinus rhythm in medically treated patients, we prospectively used this technique for 120 consecutive episodes in a total of 110 patients (94 male, 16 female, mean age 63 +/- 14 years). Structural heart disease was present in 77%, and all patients were receiving antiarrhythmic drugs at the time of the procedure. Atrial flutter type I was present in 92 of 110 patients (84%), and atrial flutter type II in 18 of 110 (16%). Primary success rate (return to sinus rhythm either immediately or after < 10 min of atrial fibrillation) was 70% (71/102) for flutter type I, and 6% (1/18) for flutter type II (p < 0.001). Delayed success (conversion to sinus rhythm in > 10 min but < 24 h) was observed in 15 additional episodes of flutter type I (15%) and in 1 additional episode of flutter type II (6%). The only clinical factors predicting primary success were (a) characteristics of flutter waves on the 12-lead surface electrocardiogram, (b) duration of flutter (primary success rate of 81% if flutter < 1 month vs. 57% if > 1 month, p < 0.05), and (c) flutter rate (primary success rate of 78% if < 260/min vs. 56% if > 260/min, p < 0.05). In 6/71 episodes of flutter type I (8%), prolonged sinus pauses or severe bradyarrhythmias occurred after conversion to sinus rhythm.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8004839 TI - Double-blind comparison of amlodipine and hydrochlorothiazide in patients with mild to moderate hypertension. AB - In the final analysis of this study at Week 26, 26% of the patients randomized to receive amlodipine attained blood pressure control with amlodipine alone compared with 33% of the patients allocated to hydrochlorothiazide (HCTZ). Neither amlodipine nor HCTZ produced clinically significant changes in pulse rate or in the electrocardiogram. Amlodipine treatment did not appear to produce clinically significant changes in blood lipids; HCTZ, however, produced an increase in total plasma cholesterol (delta 22.9 +/- 8.6 mg/dl). The incidence of side effects and the rate of patient withdrawal in the amlodipine and HCTZ groups were comparable. As expected, HCTZ therapy caused well-recognized biochemical alterations in cholesterol and potassium levels, whereas amlodipine was metabolically neutral. PMID- 8004840 TI - Effect of left ventricular contractile performance on passive left atrial filling -clinical study using radionuclide angiography. AB - Many invasive and noninvasive methods have been used to study the cardiac atria; however, few allow quantitative measurement of atrial function. To determine the interaction between left ventricular (LV) contraction and left atrial (LA) filling, gated radionuclide angiography was conducted in 30 normal subjects (24 men and 6 women, mean age 58 +/- 10 years, range 26-68). LV and LA time-activity curves and their first-derivative curves were obtained simultaneously by using the method of Bough et al. The LV ejection fraction (64 +/- 18%) and LV peak ejection rate (LVPER; 3.42 +/- 0.27 EDV/s) were computed from these curves. As indices of LA filling, LA fractional emptying (38 +/- 12%) and LA peak filling rate (LAPFR; 2.86 +/- 0.17 LAVmax/s)--the latter being defined as the peak rate of LA filling during the LA filling phase--were also computed from these curves. In all subjects, the timing of the LVPER coincided with the occurrence of LAPFR, and there was a significant positive correlation between the LVPER and LAPFR (r = 0.81, p < 0.001), indicating that the LAPFR was strongly affected by the degree of LVPER. Thus, these results indicate that LV contractile performance plays an important role in determining LA passive filling during ventricular systole. PMID- 8004841 TI - Bisoprolol, a once-a-day beta-blocking agent for patients with mild to moderate hypertension. AB - The 24-h blood pressure control of bisoprolol, a new beta-selective, beta blocking agent, was studied in 240 mild to moderate hypertensive patients in this 4-week, randomized, double-blind, placebo-controlled trial. A once-daily dosing schedule was evaluated by comparing bisoprolol's antihypertensive effectivness and safety at 24 h postdose and 3 h postdose, the latter time intended to correspond to peak effectiveness. Results from this trial demonstrated the antihypertensive effectiveness of once-daily bisprolol at doses ranging from 5-20 mg. Mean reductions from baseline diastolic blood pressure, measured 24 h postdose, were 6.3, 8.8, and 10.1 mmHg for patients receiving bisoprolol 5, 10, and 20 mg, respectively, compared with 1.6 mmHg for placebo-treated patients (p < 0.01); mean reductions from baseline systolic blood pressure for the bisoprolol groups were 8.6, 8.6, and 10.9 mmHg, respectively, versus 3.3 mmHg for placebo (p < or = 0.01); and mean reductions from baseline heart rate for the bisoprolol groups were 5.1, 7.1, and 10.2 beats/min, respectively, compared with a 0.9 beats/min increase in heart rate for the placebo group (p < 0.01). The response rates for bisoprolol-treated patients ranged from 47 to 70% compared with 18% for patients on placebo (p < 0.01). Antihypertensive effects were dose-related and sustained over the 24-h dosing interval. Near maximal antihypertensive effects were achieved within 1 week of initiation of therapy with bisoprolol and were sustained over the course of the trial.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8004842 TI - Idiopathic dilated cardiomyopathy. AB - A 43-year-old man had a 9-year history of congestive heart failure manifested by an enlarged heart and symptoms of shortness of breath and chest discomfort. Heart failure had been preceded by a "viral illness" and he had been a heavy alcohol user until that time. Autopsy showed congestion and edema characteristic of heart failure and cardiomegaly with biventricular dilatation. Either viral or alcoholic disease, or both, could have been the cause of the cardiac problems. PMID- 8004843 TI - The Osborn wave of hypothermia in normothermic patients. AB - The Osborn wave (also referred to as "the J wave," "the J deflection," or "the camel's hump") is a distinctive deflection occurring at the QRS-ST junction of approximately 80% of hypothermic patients (core body temperature < or = 95 degrees F). Generally, the amplitude and duration of Osborn waves are inversely related to core temperature. We report on eight normothermic patients whose 12 lead electrocardiograms demonstrated QRS-ST junction notches similar to those seen in hypothermia. These data support the concept that the Osborn wave is not pathognomonic of hypothermia. PMID- 8004844 TI - Familial cardiac and skeletal myopathy associated with desmin accumulation. AB - We describe the case of a mentally retarded young man with marked biventricular hypertrophy, skeletal myopathy, and bilateral pes cavus, in whom desmin accumulation was documented in cardiac and skeletal muscle biopsies. Hemodynamic assessment showed a restrictive profile. A brother of the proband was similarly affected and died at the age of 24 of cardiac failure. Sudden death occurred in other six members of this family. Pedigree analysis suggested an X-linked inheritance. This observation and previous reports suggest that desmin accumulation is probably less rare than was thought in patients with unexplained hypertrophic or restrictive cardiomyopathies. Desmin accumulation should be systematically searched for in these types of cardiomyopathies, although its specificity needs to be investigated in further studies. PMID- 8004845 TI - William R. Milnor: teacher, scientist, administrator, friend. PMID- 8004846 TI - Variation of rheological properties of the human rectal wall with distending volume. AB - Pressure-relaxation curves of in vivo human rectal wall were studied in 30 normal children for 5 volumes of distension, 10-50 ml, to define the conditions of application of the quasi-linear viscoelastic law. Three normalization methods were compared: the use of the maximum pressure of the curve, the use of the first measured point after the rectal distension, and the use of the passive state defined as the inferior envelope of the experimental curve. Analysis of variance with repeated measures was used for data analysis. It was shown that: i) the first relaxation curve, corresponding to a 10-ml distension volume, was significantly different from the other curves (p < 0.0001); ii) the quasi-linear viscoelastic law could be applied to the in vivo determination of the mechanical properties of the rectal wall, when considering the mean level of the measured points; and iii) the shapes of the experimental curves at different level of distension were significantly different (p < 0.0001). We conclude that the hypothesis of quasi-linearity is appropriate, in a first approximation, as a model of rheological properties of the rectal wall. PMID- 8004847 TI - The duty to exclude: excluding people at undue risk from research. AB - The clinical trial is the major investigational tool of clinical medicine. Two recent reports highlight the fact that the most often quoted mechanisms for the protection of research subjects, viz., research ethics board review and eligibility criteria, are insufficient to achieve this end. In this paper, we argue that the prime mechanism for the protection of persons in clinical trials should be the clinical judgement of the physician-investigator. The clinical investigator has a duty to protect subjects from both harm and undue risk. It is argued that the clinical investigator has a duty to screen for, and exclude, potential research subjects who may be unduly vulnerable to the risks of a particular clinical trial. In order to fulfill this obligation, the investigator should personally screen each potential research subject at the time of accrual. In larger trials in which this is not feasible, this task could be delegated to another appropriately qualified health care professional, with the principal investigator retaining personal responsibility. To reinforce and make explicit this legal and moral duty, we propose that the investigator sign a statement, appended to each subject's consent form, to attest that this duty has been responsibly discharged. PMID- 8004848 TI - Nephrocalcinosis in X-linked hypophosphataemic rickets: its relationship to treatment, kidney function, and growth. AB - We studied 25 patients treated with oral phosphate and 1,25(OH)2 vitamin D for 0.5-15 y (mean, 7 y) to determine the incidence of nephrocalcinosis and its relationship to treatment, renal function, and growth. During the follow-up period, 3 hypercalcaemic and 13 random hypercalciuric episodes were documented. Creatinine clearances and urine concentration tests were normal in all patients. One patient's 24-h urine specimen indicated hypercalciuria. Kidney ultrasonography revealed nephrocalcinosis in 80% of the patients, but its severity was not significantly related to the dose of calcitriol or of phosphate, the duration of treatment, the age at which treatment was started, or growth. None of the 9 untreated affected family members had nephrocalcinosis. Longitudinal studies revealed that the greatest loss in height velocity occurred during the first 2 y of life. Our study shows that nephrocalcinosis is a common complication of phosphate and 1,25(OH)2D3 treatment, but it is not necessarily associated with impaired renal function. Although the treatment failed to prevent a decrease in height velocity during infancy, it effectively maintained height velocity after 2 y of age. PMID- 8004849 TI - Nephrocalcinosis in X-linked hypophosphataemic rickets: just how serious is the problem? PMID- 8004850 TI - Refocusing health care systems to address both individual care and population health. AB - Population health depends on a qualitatively different set of investigative methods, decision-making procedures, and assignment of responsibility for action than those applied in the health care systems of Canada today. The focus shifts from a major preoccupation with acute and curative medicine to a greater concern with disease prevention and health promotion, from health outcomes as ends in themselves to quality of life concerns defined not just by the individual but also by the community. To achieve this refocusing, the health care system must decentralize the decision-making processes from provincial to regional and community levels, reorient the medical schools and hospitals from their increasingly global orientation to a greater role in the promotion of health in their own communities, and engage a broader range of disciplines and non-medical groups in partnerships and coalitions for health research and action. PMID- 8004851 TI - [Research on factors determining health: role of the environment in the 21st century]. AB - During the next few decades, actions on matters dealing with environmental pollution will have to be aimed at: 1) eliminating environmental contaminants at the source; 2) identifying biomarkers of exposure and/or adverse health effects; 3) improving our skills at assessing the probability of occurrence of adverse health effects in the community; and 4) informing the Canadian public in a responsible manner. Primary sources of pollution related to human activities should be our deep concern: utilization of energy sources, particularly fossil fuels; agricultural activities, such as deforestation and use of fertilizers and pesticides; and industrialization, responsible for the synthesis of numerous new molecules. Clinical investigators will be faced with rare disease entities characterized by low-level, long-term exposure via food, air, water and soil, and low-incidence responses (e.g. cancer, neurotoxicity, reproductive failure, immunotoxicity). Epidemiologists and toxicologists will be pressed, by the Canadian public, to answer questions regarding the probability of occurrence of health effects as a result of exposure to environmental contaminants. Collectively, as scientists, our attitudes will have to change drastically; high in the order of importance is the need to communicate with the public and to diligently inform our fellow citizens about the relationship between health and environment. In doing so, we might find allies to support our claim that health research in Canada deserves much better support. PMID- 8004852 TI - Legal liability of physicians in medical research. AB - The intent of this paper is to provide an overview, in layperson's language, of the concepts in law which may be applicable to a physician who undertakes research. The paper is divided into 2 parts. Part I deals with liability issues and standards of care. It is meant to enable the physician/researcher to recognize a potential liability situation. Part II examines insurance and related issues such as the role of the Canadian Medical Protective Association (CMPA). The paper begins with a review of 2 potential categories of liability: criminal and civil tort. Next, legal issues surrounding the consent process, which form the majority of negligence claims, are dealt with. The research process is then discussed with emphasis on the Medical Research Council of Canada Guidelines on Human Experimentation. Part II covers how research projects are funded and identifies the parties from whom insurance coverage may be sought. Information is provided from the various sources offering insurance and quasi-insurance protection with special attention on the CMPA. Each source details the circumstances necessary for its particular coverage to be triggered. Other issues addressed include those arising when research is conducted outside Canada and multiple coverage. PMID- 8004853 TI - Forearm vascular responsiveness to prolonged venous occlusion in normal subjects. AB - Fourteen normal subjects (18-42 y) were studied using venous occlusion plethysmography to investigate the characteristics and reproducibility of the forearm vasoconstrictor response following a prolonged venous occlusion stimulus. Upon release of the stimulus, a transient vasodilation is followed by a vasoconstriction. As the stimulus of venous occlusion pressure increased (40, 60, 80, and 100 mmHg for 5 min), there was a significant increase in maximum flow (p = 0.01). Minimum relative flow (minimum divided by control) was unchanged except at the highest occlusion pressure (0.49 +/- 0.05, 0.38 +/- 0.04, 0.47 +/- 0.07, 0.66 +/- 0.12, p = 0.04). As venous occlusion duration increased (3, 4, 5, and 6 min at 80 mmHg), there was no significant change in minimum relative flow (p = 0.73). With increasing ambient temperature (18, 23, and 28 degrees C), there were no significant changes in maximum or minimum relative flows (p = 0.40 and 0.25, respectively). Minimum relative flow was not significantly altered following occlusion with a 2.5-cm cuff vs. a 10-cm cuff (p = 0.77). Thus, the vasoconstriction response was reproducible over a range of venous occlusion stimuli and experimental conditions. We conclude that dynamic vascular responsiveness to prolonged venous occlusion can be measured by venous plethysmography and that calculation of the minimum flow relative to control flow is an appropriate and reproducible index of the vasoconstrictor response. Based on our studies and to conveniently measure these changes, we recommend a 10-cm venous occlusion cuff, with a pressure < or = 80 mmHg, for durations < or = 5 min, in an ambient temperature of 23 degrees C. PMID- 8004855 TI - Intrinsic modifications of the brachial and radial arteries in hypertensive humans. AB - The properties of vessel walls of brachial and radial arteries were studied noninvasively, using 2 original pulsed ultrasound echo-tracking systems based on Doppler shift, in an investigation comparing 32 normotensive controls and 50 age matched hypertensive patients. The 2 groups did not differ with respect to sex, total and high-density lipoprotein cholesterol, blood glucose, and smoking habits. Whereas noninvasive measurements of blood pressure indicated that both mean arterial pressure and pulse pressure were significantly increased in the arterial tree of the hypertensive forearm, end-diastolic diameter and pulsatile changes of the brachial and radial arteries remained within the normal range. The finding was more pronounced at the site of the radial artery in which: (i) pulsatile changes of blood pressure (documented from Finapres method) were significantly higher than those of the brachial artery, yet (ii) indices of arterial stiffness (compliance and distensibility) remained within the normal range. For the branchial artery, distensibility was significantly reduced (p = 0.01), whereas no significant change in compliance was observed. The study provides evidence that, in subjects with essential hypertension, the mechanical properties of the brachial and the radial arteries are not exclusively related to the level of blood pressure, and differ according to the arterial segment studied. PMID- 8004854 TI - The feasibility and efficacy of early discharge planning initiated by the admitting department in two acute care hospitals. AB - To determine the feasibility and efficacy of early discharge planning, initiated by admitting department personnel, a randomized, controlled trial was undertaken in 2 acute care, university-affiliated hospitals. The intervention tested was referral of patients by admitting personnel to nursing, social work, physiotherapy, occupational therapy, or dietary services for potential discharge planning. A 1-page, 65-item questionnaire was designed to identify patients for referral to the various allied health services. A copy of this was sent to the appropriate service, according to predefined criteria. The questionnaire took an average of 4 min to complete. The criteria used were highly predictive of length of stay, the most important being age, followed by living outside St. John's, admission within the previous 3 months, emergency admission, and being in need of community services. In Hospital A, the cases (n = 421) referred for early discharge planning had significantly shorter length of stay (Mantel-Cox, p = 0.03) than controls (n = 420), who were identical for all factors predictive of prolonged length of stay. The reduction in length of stay amounted to a mean of 0.8 d. In Hospital B (n = 758), the intervention was less effective because of a lower proportion of patients with factors associated with prolonged hospital stay and, perhaps, because of inadequate implementation of the program. We conclude that identification, by admitting department personnel, of patients who may benefit from early discharge planning is feasible. This process will reduce length of hospital stay, but its effectiveness is dependent on case mix variables and enthusiastic implementation of the program. PMID- 8004856 TI - Matched ventilation-perfusion becomes mismatched ventilation-perfusion lung imaging after resolution of carcinoma of the bronchus. AB - Airway occlusion results in regional alveolar hypoxia followed by reflex hypoxic pulmonary arterial constriction. Ventilation-perfusion imaging demonstrates matched defects. In the two patients reported, occlusion of the main bronchus by bronchogenic carcinoma was resolved--in one case by radiation therapy, and in the other by removal of the tumor mass in the bronchus by bronchial slitted biopsy. The initially matched ventilation-perfusion findings became mismatched. While ventilation was presumed to be normal, pulmonary perfusion was not completely reversed. PMID- 8004858 TI - Contribution of ventilation and perfusion lung imaging to the management of patients with bronchiectasis. AB - Sixty patients were studied with ventilation-perfusion (V-P) lung scans for suspected bronchiectasis. Bronchography showed bronchiectatic changes in 51 patients. Lobar and segmental matched defects were seen on V-P scans in 53 patients, of which only 46 were true positives (sensitivity 90%). V-P lung scans showed the site and extent of bronchiectatic lesions; 48 (72.7%) in the left lung and 18 (27.3%) in the right lung. Detection of associated chronic obstructive airway disease by V-P scans in 17 patients had prognostic value in postsurgery recovery time and improvement of symptoms. This may be a potential new application to the routine use of V-P lung scan in the presurgery work-up of patients with bronchiectasis. Our results showed that bronchography should not be performed on patients with preserved lung perfusion. PMID- 8004857 TI - Diffuse thallium lung uptake in Pneumocystis carinii pneumonia. AB - Five patients with AIDS with Pneumocystis carinii pneumonia (PCP) showed diffuse bilateral lung uptake on sequential thallium and gallium scans. This creates a problem in the sequential use of these tests for the differentiation of Kaposi's sarcoma from acute inflammatory or other malignant diseases. In Kaposi's sarcoma, thallium uptake is usually focal and not diffuse unless associated with other pathology. However, in PCP the diffuse thallium lung uptake may be due to congestion, increased vascular permeability, and extravasation of thallium into the lung parenchyma. PMID- 8004859 TI - False-positive Meckel's imaging and true-positive imaging of a gastrointestinal bleed and surgical lesion. AB - A 76-year-old woman presented after 1 day of melena and anemia. A Meckel's scan revealed an upper mid abdominal focus of activity that paralleled stomach activity. Later, the surgeon removed the corresponding lesion in the mid ilium. Pathology confirmed that the lesion was a carcinoid tumor, not ectopic gastric mucosa. The false-positive Meckel's scan had revealed the true source of gastrointestinal bleeding and an unsuspected solitary carcinoid tumor. This is the third published case of a carcinoid tumor discovered by a false-positive Meckel's scan. PMID- 8004860 TI - The potential use of I-123 IMP scintigraphy for pelvic bone metastases in hepatocellular carcinoma. A comparison with Ga-67 scintigraphy. AB - Conventional bone scintigraphy is often inconclusive in detecting bone metastases of hepatocellular carcinoma, suggesting the necessity of alternative scintigraphic agents. In this study, the diagnostic value of I-123 IMP scintigraphy was evaluated in 8 patients with 12 pelvic bone metastases from hepatocellular carcinoma, then compared with Ga-67 scintigraphy. Eleven of 12 lesions (91.7%) were detected by I-123 IMP scintigraphy; Ga-67 scintigraphy visualized 8 lesions (66.7%) in the same patient population. I-123 IMP scintigraphy is useful for detecting pelvic bone metastases of hepatocellular carcinoma with less physiologic accumulation in the intestine as compared with Ga 67 scintigraphy. PMID- 8004861 TI - Scintigraphic findings of osteomyelitis after intraosseous infusion in a child. AB - A case of unilateral tibial osteomyelitis in a 20-month-old child after bilateral intraosseous infusion (IOI) needle placement is presented. A review of the indications, potential complications, and scan findings is discussed. This case also shows the lack of significant uptake in the noninfected side, suggesting that a three-phase bone scan is of value in differentiating reactive bone from infected bone in patients with IOI. PMID- 8004862 TI - The relationship among the quantitative perfusion-defect indices in Tc-99m HMPAO brain SPECT, IQ test, and involved extremities in children with cerebral palsy due to perinatal asphyxia. AB - Brain SPECT imaging was performed in 13 children with cerebral palsy (6 girls, 7 boys; age, 7-17 years) due to perinatal asphyxia with mental retardation and involved limbs were studied. The involved coronal slices were summated to a picture for the calculation of the perfusion defect indices as the quantitative and objective estimation of the perfusion defects in each brain. The records of IQ tests were scored from severe to mild mental retardation. Two experienced nuclear medicine physicians analyzed the results of the Tc-99m HMPAO brain SPECTs by visual interpretation. The involved limbs were judged by two pediatricians to be either the right or left side. The relationship among the Tc-99m HMPAO brain SPECTs, IQ test, and physical examinations of the extremities were established. The results showed that two cases of mild mental retardation had the smaller perfusion defect indices (< 0.1), six cases of severe mental retardation had the larger perfusion defect indices (> 0.30), and the other group was between the first two groups. Two cases of mild mental retardation did not have significant perfusion defects in the brain and involved limbs, and two cases with decreased visual acuity had definite perfusion defects in the occipital regions. The other cases had the matched perfusion defects of the brain with the involved limbs. The authors encourage the potential use of Tc-99m HMPAO brain SPECTs to predict the outcome of mental development and limb involvement. PMID- 8004863 TI - Clinical evaluation of Tc-99m cystine. A new renal radiopharmaceutical. AB - Tc-99m cystine has been proved to be a good renal agent in animals. Its clinical evaluation has not been reported. In this study, Tc-99m cystine is used for evaluation of renal function in normal subjects and patients with chronic renal failure as well as in renal transplant patients. The results are compared with similar studies using Tc-99m DTPA and Tc-99m GHA. The clearance values also are compared with I-131 OIH. The results show that Tc-99m cystine has good radiopharmaceutical characteristics suitable for evaluation of both renal function as well as morphology. PMID- 8004865 TI - False-positive radioiodine whole-body scan in thyroid cancer patients due to unrelated pathology. AB - Radioiodine whole-body scanning is the imaging modality of the highest accuracy in diagnosing metastases from differentiated thyroid cancer. However, unrelated pathology in one of several nonthyroidal tissues that normally take-up/secrete radioiodine may result in a false positive scan. The authors report cases of an ectopic kidney, chronic sinusitis, dacryocystitis, and an artificial eye, complicating differentiated thyroid cancer, that on radioiodine scanning mimicked lumbar, frontal, and left and right orbital bone metastases, respectively. The nature of the radioiodine uptake was suspected from the results of a bone scan and proven by ultrasound (ectopic kidney), by reimaging after specific treatment (chronic sinusitis, and dacryocystitis), or by postwashing reimaging (artificial eye). To our knowledge, this is the first report of such cases. Nonthyroidal pathology should be excluded before exposing patients with apparent thyroid cancer metastases that have atypical characteristics on radioiodine whole body imaging. PMID- 8004864 TI - A rare portosystemic shunt detected by MRI and diagnosed by dynamic liver scintigraphy with Tc-99m phytate. AB - Although various types of portosystemic shunts with portal hypertension have been widely reported, a collateral circulation near the pancreas head is rare. The authors report a case of a rare portosystemic shunt surrounding the pancreatic head, which was diagnosed by dynamic liver scintigraphy using Ikoma's scintigraphic criteria for the presence of portosystemic shunts. According to these criteria, abnormal accumulation of radioactivity at various abdominal sites (not identified on static images after the dynamic study) on 6 or more continuous frames of 5-second intervals (i.e., for 30 seconds or more after the arterial phase) indicates the presence of a portosystemic shunt. If liver scintigraphy is performed on a patient with portal hypertension, the dynamic study is valuable in the detection and diagnosis of a portosystemic shunt. PMID- 8004866 TI - Acute organophosphate poisoning--Tc-99m HMPAO SPECT imaging of the brain. A report of two cases. AB - Two cases of organophosphate poisoning are presented along with Tc-99m HMPAO brain SPECT findings in the acute and delayed phases. Perfusion defects were more prominent at the onset of poisoning in both cases. PMID- 8004867 TI - Thallium-201 uptake in keloid tissue masquerading as a pulmonary neoplasm. AB - Tl-201 imaging is useful in the diagnostic work-up of tumors. However, Tl-201 uptake is not specific for tumor and is also noted in other conditions. A case is described in which Tl-201 was taken up by a keloid. PMID- 8004868 TI - Normal qualitative and quantitative Tc-99m sestamibi myocardial SPECT: spectrum of intramyocardial distribution during exercise and at rest. AB - Exercise myocardial perfusion imaging with Tc-99m sestaMIBI is routinely used to detect underlying coronary stenoses. Ischemia is diagnosed in regions that display decreased tracer uptake during exercise as compared to rest. Tc-99m sestaMIBI SPECT images of 42 healthy volunteers were assessed both qualitatively (tomographic slices) and quantitatively (sectored polar map) for potential sources of misinterpretation. On the myocardial tomographic slices, the most common culprit artifacts were diaphragmatic attenuation and bowel interposition, which caused fixed or reversible "perfusion defects" in the inferior and posterior regions (in 19/35 abnormal segments), and artifacts related to the presence and shift of hot spots (observed in 11/28 men; in women, they were more difficult to demonstrate because of the overriding effect of breast attenuation). Hot spots shifts between exercise and rest usually resulted in pseudo-reversible defects in the anterolateral and lateral walls. The quantified polar map display of the myocardium showed a physiologic decrease in sestaMIBI activity in the basal anterolateral and basal posterolateral areas in men during exercise. There are many normal variants that may mimic coronary artery disease on tomographic sestaMIBI images. Before reporting an area of decreased activity as either a fixed or reversible perfusion defect, the interpreter should ensure that it does not represent an artifact or a normal variation in the intramyocardial distribution of sestaMIBI during exercise. PMID- 8004870 TI - Dramatic improvement of soft tissue uptake of liver metastases on bone imaging. PMID- 8004869 TI - Myocardial perfusion imaging with pharmacologic stress in a 9-year-old girl. PMID- 8004871 TI - Intestinal uptake of Tc-99m MDP in a patient with vipoma syndrome. PMID- 8004872 TI - Scintigraphic appearance of primary skeletal leiomyosarcoma. PMID- 8004873 TI - Superior vena cava syndrome due to a substernal nontoxic goiter. PMID- 8004875 TI - Extraskeletal localization of MDP in soft tissue secondary to methotrexate infiltration. PMID- 8004874 TI - Tc-99m HMPAO labeled leukocyte uptake by an inflammatory fibroid polyp of the ileum. PMID- 8004876 TI - Changes in intracardiac shunt elicited by pneumonia. PMID- 8004877 TI - Page kidney phenomenon in allograft transplant. PMID- 8004878 TI - New drug development in the United States from 1963 to 1992. PMID- 8004879 TI - Estimating bioavailability when clearance varies with time. AB - The influence of interoccasion variability in clearance on bioavailability estimates from a traditional two-period crossover design is reported for five methods of analysis: (1) the standard crossover analysis, (2) a groupwise, parallel, analysis, (3) and (4) two correction procedures suggested by J.G. Wagner and by P.S. Collier and S. Riegelman, and (5) a pharmacokinetic nonlinear mixed-effects model analysis. Three bioavailability parameters are considered the population mean bioavailability (F), the interindividual variance of bioavailability (omega 2F) and the correlation of bioavailability with clearance [cor (CL,F)]. Data are simulated with different degrees of interoccasion variability and/or non-zero cor(CL,F). With the standard crossover analysis of these data, estimates of F, omega F, and cor(CL,F) are all biased in the presence of interoccasion variability in clearance. Estimates of F and omega 2F obtained from the parallel-group analysis are not reliable because the approach relies on the assumption that cor(CL,F) is zero. The two correction procedures are very sensitive to random error in the estimates of terminal half-life. The mixed effect model approach produces unbiased estimates of all three bioavailability parameters. These results from simulations are supported by a real data example. PMID- 8004881 TI - Acute-phase response, interleukin-6, and alteration of cyclosporine pharmacokinetics. AB - OBJECTIVE: Administration of interleukin-6 partially reproduces the inhibitory effects of the acute-phase response on cytochrome P450-dependent drug metabolism. The aim of the study was to determine whether endogenous cytokine has such an effect in patients treated by cyclosporine, which is metabolized by the cytochrome P4503A subfamily. METHODS: Blood cyclosporine and serum interleukin-6 levels were determined in six patients undergoing bone marrow transplantation, as long as they received cyclosporine by continuous infusion. Two serum acute-phase proteins, C-reactive protein and alpha 1-acid glycoprotein, and two cyclosporine metabolites, AM1 and AM9, were also determined. RESULTS: At the time of marrow infusion, levels of specific markers of inflammation were low. A peak in interleukin-6 level was then observed a mean of 10.8 days after transplantation, closely associated with variations in C-reactive protein levels. A parallel twofold increase in AM1 concentrations was observed, followed by a three-fold increase in cyclosporine levels, which peaked 4.8 days after interleukin-6. The times of peak cyclosporine and AM1 levels correlated with the time of peak interleukin-6 levels. AM9 was detectable in three patients but concentrations fell when interleukin 6 became detectable. CONCLUSIONS: An inflammatory reaction could be an important source of intraindividual variability in cyclosporine pharmacokinetics, possibly through an inhibition of cytochrome P4503A-dependent enzyme activities by endogenous interleukin-6. Blood AM1 accumulation might be explained by a secondary metabolic step that is highly sensitive to the inhibitory effect of interleukin-6. PMID- 8004880 TI - Pharmacokinetics and pharmacodynamics of recombinant factor VIIa. AB - OBJECTIVE: To evaluate the pharmacokinetics and pharmacodynamics of recombinant activated factor VII (rFVIIa). METHODS: Single-dose pharmacokinetics of three dose levels (17.5, 35, and 70 micrograms/kg) of rFVIIa were investigated in 15 patients with hemophilia with severe factor VIII or factor IX deficiency (with or without inhibitors) while they were in the nonbleeding state and during bleeding episodes. Factor VII clotting activity (FVII:C) was determined 5 minutes before and at 10, 20, and 50 minutes and 2, 4, 6, 8, 12, and 24 hours after rFVIIa administration. Model-independent pharmacokinetic analysis of FVII:C plasma concentration-time data included determination of plasma clearance, mean residence time, and volume of distribution. rFVIIa recovery was determined from the plasma FVII:C observed 10 minutes after administration. Pharmacodynamic assessments of prothrombin time, activated partial thromboplastic time, and Factor X values obtained concurrently with FVII:C samples were performed. RESULTS: Sufficient data to allow pharmacokinetic parameter calculation were available for 25 nonbleeding episodes in 11 patients (17.5 micrograms/kg, n = 8; 35 micrograms/kg, n = 9; 70 micrograms/kg, n = 8) and for five bleeding episodes in three patients (17.5 micrograms/kg, n = 2; 35 micrograms/kg, n = 2; 35 micrograms/kg, n = 1). Recovery was calculated during 27 nonbleeding and 17 bleeding episodes. rFVIIa distribution volume is two to three times that of plasma. Median clearance was low--31.0 ml/hr.kg in nonbleeding episodes and 32.5 mg/hr.kg in bleeding episodes. In nonbleeding episodes, median mean residence time was 3.44 hours and median half-life was 2.89 hours. In bleeding episodes, the elimination rate appears to be higher, with a median mean residence time of 2.97 hours and a median half-life of 2.30 hours. Recovery was 45.6% during nonbleeding conditions and 43.5% during bleeding episodes (p = 0.0006); it was statistically lower with the highest dose level than with the 17.5 and 35 micrograms/kg doses (p = 0.007). A significant statistical relationship was observed between values of the prothrombin time and activated partial thromboplastin time, and values of FVII:C with use of maximum effect model. CONCLUSIONS: The pharmacokinetics of rFVIIa are linear in the dose range evaluated. The results suggest potential value of prothrombin time determination in the monitoring of rFVIIa therapy. PMID- 8004882 TI - Pharmacokinetic and pharmacodynamic interactions during multiple-dose administration of nisoldipine and propranolol. AB - OBJECTIVES: The pharmacokinetic and pharmacodynamic interactions after 7 days of oral treatment with nisoldipine (10 mg twice daily) and propranolol (80 mg twice daily) were investigated in a partially randomized, placebo-controlled crossover study of 12 healthy volunteers. METHODS: At the end of each treatment period, pharmacokinetic parameters were measured, along with blood pressure, heart rate, cardiac function, systemic hemodynamics, plasma catecholamines, forearm blood flow, and apparent hepatic blood flow (estimated by the clearance of indocyanine green dye). RESULTS: After 7 days of treatment with nisoldipine and propranolol, neither drug altered the other's bioavailability or elimination parameters, and propranolol did not change the area under the plasma concentration-time curve of nisoldipine's metabolite, N-9425. Nisoldipine alone increased apparent hepatic blood flow and forearm blood flow compared with the other treatment groups but, with the addition of propranolol, both of these parameters were similar to those in the placebo group. Changes in the other hemodynamic parameters were consistent with the known effects of these drugs, and no differences in plasma catecholamine levels were detected. CONCLUSIONS: In contrast to the findings with single-dose treatment, administration of the combination of nisoldipine and propranolol for 7 days is not associated with any measurable kinetic interactions, although significant hemodynamic interactions do occur. PMID- 8004883 TI - Cinnarizine in the prophylaxis of seasickness: laboratory vestibular evaluation and sea study. AB - Cinnarizine was evaluated for the prevention of seasickness in a laboratory and sea study. The effects of 25 mg cinnarizine on the vestibulo-ocular reflex were investigated in 13 subjects. Significant reduction of the gain in response to sinusoidal oscillations at 0.02, 0.08, and 0.16 Hz (p < 0.05) and increased phase lead at 0.16 Hz (p < 0.01) were observed. The effect of 25 and 50 mg cinnarizine on seasickness severity was examined in 95 subjects during a voyage in rough seas. Seasickness symptoms were improved in 69% of the subjects by 50 mg cinnarizine versus 35% and 31% in the groups receiving 25 mg cinnarizine and placebo (p < 0.05 and p < 0.01, respectively). The percentage of vomiting protection provided by 50 mg cinnarizine was 63% (p < 0.05). We conclude that 50 mg cinnarizine is an effective drug for the prevention of seasickness. The reduction in vestibular sensitivity observed even after administration of 25 mg cinnarizine may explain the potency of cinnarizine in the prevention of seasickness. PMID- 8004884 TI - Effect of intravenous L-carnitine on carnitine homeostasis and fuel metabolism during exercise in humans. AB - This study was undertaken to challenge the hypothesis that short-term administration of carnitine during exercise can modify skeletal muscle carnitine homeostasis and fuel metabolism in normal humans. With a randomized, blinded, crossover design, subjects received carnitine or placebo at the start of a bicycle ergometer exercise session. During the 2 hours after intravenous administration of 185 mumol/kg carnitine, carnitine kinetics could be described with a central compartment volume of distribution of 200 ml/kg, a total clearance from this compartment of 1.9 ml/min/kg, and a renal clearance of 1.3 ml/min/kg. Carnitine administration had no effect on muscle total carnitine content or the workload-dependent accumulation of acylcarnitines in skeletal muscle. Carnitine had no effect on the respiratory exchange ratio, muscle lactate accumulation, plasma lactate concentration, muscle glycogen utilization, or plasma beta hydroxybutyrate concentration during exercise. Thus the skeletal muscle carnitine pool is segregated from dramatic changes in the plasma carnitine pool, and short term administration of carnitine has no significant effect on fuel metabolism during exercise in humans. PMID- 8004885 TI - Famotidine-associated central nervous system reactions and plasma and cerebrospinal drug concentrations in neurosurgical patients with renal failure. AB - Central nervous system toxicity of H2-receptor antagonists has rarely been confirmed by the respective elevated cerebrospinal fluid drug concentrations. We observed two hemodialyzed neurosurgical patients in whom mental deterioration and convulsions developed after intravenous famotidine therapy (10 and 40 mg/day). Their cerebrospinal fluid drug concentrations were grossly elevated (i.e., 160 and 249 ng/ml) compared with those obtained from three other hemodialyzed neurosurgical patients who exhibited no central nervous system reactions (i.e., 47 to 85 ng/ml). In addition, the mean cerebrospinal fluid/plasma drug concentration ratio obtained from these five neurosurgical patients with renal failure (i.e., 0.46) and that from 10 other neurosurgical patients with normal renal function (i.e., 0.41) were about four times greater than that previously reported from non-neurosurgical patients with normal renal function (i.e., 0.12). Our observation suggests that patients with not only renal dysfunction but also following neurosurgical operations have an excessive accumulation of famotidine in the central nervous system and are more susceptible to the drug-induced adverse central nervous system reactions. PMID- 8004886 TI - Acute spinal trauma: prognostic value of MRI appearances at 0.5 T. AB - Thirty-two patients with post-traumatic myelopathy were examined with a 0.5 T MRI system within 4 days of injury and the MRI findings analysed with respect to the immediate and residual functional deficit and (in 20 patients) the MRI appearances of the spinal cord in the chronic phase. In the acute phase a normal spinal cord was associated with only slight clinical deficit in four patients. Signal abnormalities in the spinal cord at the site of trauma were identified on T2-weighted spin-echo or T2*-weighted gradient-recalled echo images in 28 patients. The 12 most functionally impaired patients showed focal low signal suggestive of intramedullary haemorrhage: the other 16 had homogeneous high signal consistent with diffuse oedema. Swelling of the spinal cord and mild persistent cord compression following reduction were noted in 17 and 26 patients respectively. All patients were treated conservatively other than undergoing surgical decompression. Four died of complications. No patient with low signal in the spinal cord on initial MRI showed significant clinical improvement. Five whose spinal cord was hyperintense remained unchanged, whereas nine made a significant recovery, as did all patients with normal-appearing spinal cords. Cord compression on the initial examination was not relevant to clinical outcome. Intramedullary scars were identified at follow-up in 18 patients and were more extensive in those with haemorrhagic acute lesions. Haemorrhagic contusion of the spinal cord can be demonstrated in the acute phase with midfield MRI and is a valuable predictor of the functional outcome in patients with traumatic myelopathy. PMID- 8004887 TI - Sonographic appearance of branchial cysts. AB - Branchial cysts are developmental anomalies arising from remnants of the foetal branchial apparatus. Two patients in whom the presence of a branchial cyst was confirmed at surgery had undergone pre-operative neck ultrasound examination. In each case the cysts showed a characteristic uniform low echogenicity. Recognition of this appearance allows prompt and appropriate further investigation and treatment. PMID- 8004888 TI - Comparison of MR and CT scanning in severe acute pancreatitis: initial experiences. AB - Magnetic resonance imaging was performed at 1.0 T in seven patients with severe acute pancreatitis. A T2-weighted spin echo sequence and a breath-hold multislice rapid gradient echo sequence (TurboFLASH) were used in each patient. TurboFLASH imaging was performed before and after intravenous gadopentetate-dimeglumine (Gd DTPA). All MRI images were compared with a recent contrast-enhanced CT scan. Postgadolinium MRI was equivalent to contrast-enhanced CT in differentiating viable pancreatic parenchyma from areas of pancreatic necrosis. MRI identified the presence of gas in a case of pancreatic abscess but failed to identify small foci of pancreatic calcification demonstrated in one case by CT. MRI was also equivalent to CT in assessing the location and extent of peripancreatic inflammatory changes and fluid collections. However, MRI, particularly the T2 weighted spin echo, was superior to CT in characterizing the complex nature of such inflammatory changes in one case. Initial experience suggests that MRI is a valuable technique in assessing patients with severe acute pancreatitis. PMID- 8004889 TI - Magnetic resonance imaging of intracranial cavernous angiomas: a report of 13 cases with pathological confirmation. AB - The magnetic resonance imaging features of 13 pathologically confirmed cavernous angiomas were retrospectively reviewed. T2-weighted images were found to be the most useful, the commonest appearance being a mixed signal intensity core with a complete peripheral rim of marked hypointensity. These appearances relate largely to various stages in the evolution of haemorrhage, although the presence of calcium and slowly flowing blood also contribute. PMID- 8004890 TI - Magnetic resonance imaging of the brain in idiopathic hypogonadotropic hypogonadism. AB - Magnetic resonance imaging (MRI) of the pituitary, hypothalamus and olfactory sulci was performed in 40 patients with idiopathic hypogonadotropic hypogonadism (IHH). Twelve of these patients had an impaired sense of smell (Kallmann's syndrome). Sagittal and coronal imaging revealed no morphological abnormalities in the hypothalamic-pituitary region. On axial imaging rudimentary, hypoplastic or aplastic olfactory sulci were found in eight cases. All patients with olfactory sulcal abnormalities had associated hyposmia (one case) or anosmia (seven cases). Structural defects identifiable on MRI were present only in 20 per cent of patients with IHH. PMID- 8004891 TI - Periportal fibrosis secondary to transfusion siderosis in two patients with acquired immune deficiency syndrome (AIDS) treated with zidovudine--a confusing ultrasound appearance. AB - We present the confusing sonographic features of periportal fibrosis in two AIDS patients who had zidovudine-induced transfusion siderosis of the liver. To our knowledge this has not been previously reported in the literature. The clinical, pathological and sonographic features are described. PMID- 8004892 TI - Are routine chest radiographs prior to angiography of any value? AB - Chest radiographs are frequently requested prior to diagnostic angiography, though there is no published evidence of their clinical utility. This study was undertaken to evaluate their contribution to patient management. The routine chest radiographs obtained prior to peripheral and coronary angiography in 240 patients were prospectively reviewed for abnormalities likely to affect management. Two hundred and twenty (91.7%) examinations were performed, of which 164 were obtained within 24 h of angiography. Previous radiographs were available in 154 patients (64.2%). One hundred and sixteen radiographs were normal. There were 117 abnormalities on the radiographs of 104 patients, mainly cardiac enlargement and heart failure. No angiogram was postponed or cancelled because of abnormalities detected on a routine radiograph, although radiographic findings led to a change in the volume of contrast medium injected into dilated aortic roots in 10 patients undergoing cardiac catheterization. Pre-angiography radiographs had no effect on the practice of peripheral angiography. In only one patient were further investigations and therapy instigated because of findings, but even in this case these findings were present on previous studies. We conclude that routine pre-angiography chest radiographs are not necessary in the absence of specific clinical indications. PMID- 8004893 TI - Case report: cerebral arteriovenous fistula in the Klippel-Trenaunay-Weber syndrome. AB - The clinical and radiological findings are presented in an adult patient with the Klippel-Trenaunay-Weber Syndrome who developed epileptic fits. Cranial computed tomography (CCT) and cerebral angiography demonstrated a cerebral arteriovenous fistula and occlusion of the straight sinus. PMID- 8004894 TI - Case report: multiple neonatal fractures--dietary or deliberate? AB - A case of multiple fractures in a 3-month-old Asian girl with rickets is presented, in which difficulty in excluding child abuse was encountered. No firm conclusions were reached, and the child later died suddenly at 5 months of age. Post-mortem confirmed rickets histologically and the principal cause of death was recorded as sudden infant death syndrome. Three years later evidence of child abuse was found against a subsequent sibling in the same family. If the typical injuries associated with child abuse are present, these must be taken as strong points in favour of this diagnosis, even in the presence of metabolic bone disease. PMID- 8004895 TI - Case report: Ewing's sarcoma in distal tibial metaphysis mimicking osteomyelitis. AB - An 11-year-old girl presented with the clinical picture of osteomyelitis of the distal tibia. A bone scintigram, although abnormal, did not confirm the diagnosis, but a 99mTc leucocyte scan showed focal white cell uptake in the distal tibia. This was felt to confirm infection and subsequent aspiration revealed what was thought to be pus. However, histology of the aspirated material demonstrated Ewing's Sarcoma. The differential diagnosis and the place of scintigraphy in this clinical situation are discussed. PMID- 8004896 TI - Case report: percutaneous retrieval of a misplaced embolization coil. AB - We report a case of percutaneous retrieval of a misplaced embolization coil which threatened the segmental arterial supply of a single kidney. The renal artery was steeply angulated due to a spinal scoliosis but retrieval was rapidly performed using an Amplatz gooseneck snare. This device is particularly useful when the arterial anatomy is tortuous. PMID- 8004897 TI - Colour flow imaging for lower limb arterial disease. PMID- 8004898 TI - The mucosal rosette: a peri-ampullary pseudotumour within a duodenal diverticulum. PMID- 8004899 TI - The mucosal rosette within a duodenal diverticulum: significance and implications. PMID- 8004900 TI - Radiology in the management of ovarian cancer. PMID- 8004901 TI - Diagnosing early ovarian cancer with ultrasound--research goal or clinical reality? PMID- 8004902 TI - Computed tomography of diffuse pulmonary haemorrhage with pathological correlation. AB - The utility of computed tomography (CT) is well established in patients with chronic interstitial lung disease. There are currently no descriptions of the CT appearances of diffuse pulmonary haemorrhage. The CT findings of six patients with diffuse pulmonary haemorrhage are presented. Pathological correlation from open lung biopsies in two of these patients provided a pathological basis for the CT appearances. All six patients had diffuse nodular opacities with no zonal predominance. The nodules were of uniform size in any single patient but varied (1-3 mm diam.) between patients. Patchy areas of 'ground-glass' opacification of the lung parenchyma due to recent haemorrhage was associated with apparent prominence of the segmental bronchi and obscured the background nodularity. The CT findings were similar in all six patients and, although not pathognomonic, awareness of the CT features described should raise the possibility of the diagnosis. PMID- 8004903 TI - The significance of pulmonary nodules detected on CT staging for lung cancer. AB - Small pulmonary nodules of soft tissue density are often found during computed tomography for the staging of lung cancer, but CT cannot reliably distinguish benign from malignant uncalcified pulmonary nodules. The purpose of this study was to assess the significance of pulmonary nodules discovered on staging CT. 551 patients with lung cancer who had a staging CT and who were considered operable were studied. Eighty-eight patients (16%) were found to have small non-calcified pulmonary nodules. Adequate follow-up was possible in 25 patients who had a total of 36 nodules. Twenty-five nodules (70%) were subsequently confirmed to be benign, four (11%) were malignant and the nature of seven (19%) could not be determined. The high prevalence of benign nodules in this population should be taken into account when staging lung cancer. PMID- 8004904 TI - Symptomatic spondylolysis: correlation of CT and SPECT with clinical outcome. AB - Twenty-seven patients with spondylolysis and back pain were considered for spinal fusion. All patients underwent clinical evaluation, multiplanar computed tomography (CT) and single photon emission computed tomography (SPECT). After clinical evaluation 12 patients were not considered suitable for fusion on clinical grounds. SPECT was normal in these patients. Fifteen underwent a trial of lumbar immobilization and nine of those rendered pain free subsequently underwent spinal fusion. The results of clinical examination, lumbar immobilization, imaging and final outcome were compared in these patients. Those patients rendered pain free by surgery all had positive SPECT scans. Those with persistent pain after surgery had negative scans. This small series suggests a positive relationship between SPECT scanning and patient outcome following fusion. These findings need to be confirmed by larger studies with longer periods of follow-up. PMID- 8004905 TI - Factors affecting the transformation of octacalcium phosphate to apatite in vitro. AB - A fresh octacalcium phosphate (OCP) precipitate without drying and three kinds of dried OCP powders were soaked for 3 weeks in 11 kinds of physiological solutions consisting of different combinations of Ca2+, Mg2+, K+, Na+, HCO3-, HPO4(2-), F-, albumin, collagen and alkaline phosphatase, in three different pH values and at three different temperatures. X-ray diffraction study showed that most of the OCP had been transformed to apatite with low crystallinity after soaking in the solutions without Mg2+. The IR absorption spectra revealed that CO3 was incorporated in the apatite formed from OCP in the solution without Mg2+, whereas OCP changed little after soaking in the solution containing Mg2+. These results suggest that the presence of Mg2+ in the solution is one of the most effective means of inhibiting the transformation of OCP to apatite by interrupting the precipitation process of apatite. PMID- 8004906 TI - Compositions of surface layers formed on amalgams in air, water, and saline. AB - The surface layers formed on both a zinc-free and a zinc-containing dental amalgam after polishing and aging in air, water, or saline, were characterized using x-ray photoelectron spectroscopy (XPS) to determine the compositions of the surface layers which might govern the release of mercury from amalgam. The XPS data revealed that the formation of the surface layer on the zinc-containing amalgam was affected by the environment in which the amalgam was polished and aged, whereas that on the zinc-free amalgam was not affected. In addition, among the elements contained in amalgam, zinc was the most reactive with the environment, and was preferentially dissolved from amalgam into water or saline. Mercury atoms existed in the metallic state in the surface layer. PMID- 8004908 TI - Corrosion of coupled metals in a dental magnetic attachment system. AB - Implants and magnetic attachments are becoming widespread in dental treatment. Their associated use, implants and magnetic attachments, can be seen often too. In those cases, it is difficult to avoid coupling of different metals. The corrosion behavior of the metals is expected to be different depending on whether it is found in an isolated or a coupled condition. Potential corrosion couples in a dental magnetic attachment system among titanium, ferromagnetic stainless steel, gold alloy type IV, and gold-silver-palladium alloy were studied by an immersion test in 1% lactic acid for 7 days and potential/current density curves were measured. Corrosion of titanium and ferromagnetic stainless steel seemed to be accelerated by coupling with gold alloys or gold-silver-palladium alloys. On the other hand, the corrosion amount of gold alloy and gold-silver-palladium alloys were attenuated by coupling. PMID- 8004907 TI - Effect of silane coupling agents with a bisfunctional hydrolyzable group. AB - Improvement of the siloxane layer on minerals by using a bisfunctional silane, such as 1,6-bis(trichlorosilyl) hexane and 1,8 bis(trichlorosilyl)octane, and the effects on adhesion of methacrylic resin to glass plates treated with the silanes were studied. The tensile bond strength of the resin to the glass plate treated with bisfunctional silane alone was high (about 20MPa) in spite of the fact that the molecule contains no double bonds. Furthermore, a mixture of bisfunctional silane and 3-methacryloxypropyltrichlorosilane showed an excellent effect for tensile bond strength and water-resistance. Based on the results, it is suggested that the better water resistant adhesion of the mixed silane depends on the higher degree of crosslinking in the siloxane phase and on the formation of an interpenetrating polymer network between the siloxane layer and the matrix resin. PMID- 8004910 TI - The extent of polymerization of Class II light-cured composite resin restorations; effects of incremental placement technique, exposure time and heating for resin inlays. AB - The extent of polymerization of light-cured composite resins cured in relatively large class II cavities was estimated by measuring Knoop hardness on sectioned surfaces of resin restorations. The influences of the incremental placement technique, exposure time, and post-curing of resin inlay on the extent of polymerization of two different resin materials were examined. For both MFR type (HE) and hybrid type (P50) materials, the 3-step incremental placement technique was superior when the cavity was restored by the direct filling method. For resin inlays, the post-heating improved the conversion of resin restorations. However, because the final degree of conversion of resin attained by heating was influenced by the initial conversion of the resin at the stage of light-curing, the 2-step incremental placement technique was recommended at the light-curing stage for even resin inlays. As the exposure time is influenced by the transmittance of material and the intensity of activator light, it should be optimized in accordance with manufacturers' directions. PMID- 8004909 TI - In vivo wear pattern of experimental composite resins based on different resin monomers. AB - This study investigated the effects of various monomer systems on composite resin wear in vivo. Experimental light-cured composite resins were prepared employing four different monomer systems: (1) Bis-GMA type, (2) D-2. 6E type, (3) UDMA type, (4) UTMA type. The resin monomers consisted of 70wt% main monomer and 30wt% TEGDMA. These composites contained 80wt% fine quartz. The resins were placed in 2 mm diameter cylindrical cavities located in the occlusal contact area or the contact free area in cast crowns, temporarily set in a mouth. The crowns were removed at monthly intervals, for longitudinal SEM observation. Two months after setting, wear was analyzed, using an electron probe surface roughness analyzer. Microabrasion of the resin matrix and loss of filler particles were observed for all types of monomer systems. The effect of matrix resin systems on occlusal wear was smaller than that of filler systems. PMID- 8004911 TI - Skin holes of titanium casting. AB - The present study describes refractories which contribute to formation of skin holes of Ti casting. Plates consisting of quartz (Qu) and cristobalite (Cr) powders and Qu- and Cr-MgO mixtures were fired at high temperatures and used as phosphate-free molds. The cross-section of the castings was investigated using an optical microscope and an electron probe microanalyzer. Whereas the castings into the Qu molds were almost complete, those into the Cr molds were incomplete. The surface reaction zone of the Qu molds formed a typical layered structure with fewer skin holes. That of the latter extended deeply into the interior with a net shaped Ti-Si phase, cracks, and holes. Addition of MgO to Cr effectively improved the castability and changed the reaction zone to the typical layered structure. However, slender holes occurred along the mold wall. The overall area around the holes was contaminated by Si and Mg. Probably, this resulted from a reaction of forsterite with Ti. The reactivity difference between Qu and Cr was not related to the fired strength of mold. PMID- 8004912 TI - Polymerization shrinkage and contraction force of composite resin restorative inserted with "Megafiller". AB - This study quantified the contraction force and polymerization shrinkage of composite resins with/without beta-Quartz Glass Ceramic Inserts (BQCI) as "Megafiller". The materials used for the determination included a chemically cured composite and five light-cured composites. The system for measuring contraction force consisted of a transparent teflon tube for preparing the specimen, a small load cell, a dynamic strain gauge and a pen-recorder. After the composite was packed into the teflon mold, a BQCI (Type R3) was inserted through the opening and the specimen was cured. Linear polymerization shrinkage of the composites was measured every 10 seconds from the start of mixing or irradiation to 90 minutes by the mercury bath method. Three pieces each of BQCI (Type T3) were inserted in each specimen. The results suggested that BQCI was markedly effective in reducing polymerization shrinkage, but was not always effective in reducing the contraction force during polymerization. PMID- 8004913 TI - Improvement of CAD to produce crown by considering occlusion. AB - Improvement of the CAD process to design the shape of crown restorations of a 6 die was carried out by including the bite data of the antagonistic tooth in addition to the data measured in the previous paper. Initially, the position adjustment of the crown data with the bite data in the centric occlusion was attempted. After fixation of the crown data to a suitable position, modulation of the occlusal surface by the functionally generated path (FGP) data was carried out. To connect between the end of the crown data and the margin, a parabolic function was used instead of the B-Spline function used in the previous paper. As a result, the data points were connected more smoothly. Thus, CAD data which were composed of the die data, the crown data, and the connecting data were accomplished. They will be used as the basic data to CAM. PMID- 8004914 TI - Application of root canal cleaning agents having dissolving abilities of collagen to the surface treatment for enhanced bonding of resin to dentin. AB - Commercial root canal cleaning agents with the ability to dissolve collagen were used for the surface treatment to enhance the bonding of dental resins. These agents increased the bond strength of a dental bonding agent to dentin. For example, the tensile bond strength to bovine dentin was 10.7 +/- 3.9MPa following the joint use of M and N and 8.8 +/- 2.2MPa following the combined use of P-S and N. In these cases, the damage to the tooth surface was very small and was equal to or less than damage caused by EDTA. These results demonstrate the usefulness of commercial root canal cleaning agents for dentin surface treatment due to their ability to enhance the bonding of dental resin. PMID- 8004915 TI - A computer simulation of the reactions between hydroxyapatite and fluoride in aqueous acidic solutions. AB - A precipitation reaction between hydroxyapatite (HAp) and fluoride solution was analyzed by computer simulation. The system comprised excess HAp and 0.05-0.2 M acetic buffer solutions containing 0.5-2.0 mM potassium fluoride. The amounts of HAp dissolved and calcium salts precipitated and activities of all the species present in the solution were calculated during the process. In the systems, calcium fluoride was initially precipitated when applying the fluoride solution to HAp, followed by precipitation of fluorapatite (FAp) and re-dissolution of the previously precipitated calcium fluoride at a critical pH at which the ion activity product exceeded the solubility product of FAp. The critical pH was increased with pH of the buffer, whereas it was scarcely affected by fluoride ion concentration, and it was necessary to introduce phosphate ions in advance into the buffer for predominant precipitation of FAp in this system. PMID- 8004917 TI - In vivo wear pattern of experimental light-cured hybrid composite resins. AB - This study evaluated the effect of various types of microfiller on the in vivo wear resistance of composite resins. Experimental light-cured composites with two different microfiller systems were prepared: (1) 56 wt % fine quartz filler, 21 wt% organic filler and 3 wt% colloidal silica filler (Hybrid type 1), and (2) 64 wt% fine quartz filler and 21 wt% colloidal silica filler (Hybrid type 2). The resin monomer consisted of 50 wt % Bis-GMA and 50 wt% TEGDMA. These materials were placed in 2 mm diameter cylindrical cavities located in the OCA (occlusal contact area) or the CFA (contact free area) in cast gold-silver-palladium alloy full coverage crowns, which were temporarily set in a volunteer patient's mouth. The crowns were removed at monthly intervals for SEM observation. Hybrid type 1, which contained organic fillers, showed bulk fractures in the OCA, by the second month of the experiment. However, reinforcement of the resin matrix by dispersion of microfiller provided Hybrid type 2 with superior wear resistance for up to two months. PMID- 8004916 TI - Efficacy of dentin bonding agents combined with self-etching dentin primers containing Phenyl-P. AB - The bonding efficacies of three commercial dentin bonding agents and an intermediate resin combined with two self-etching dentin primers (aqueous solutions of methacryloxyethyl hydrogen phenyl phosphate (Phenyl -P, 20 wt%) and either hydroxyethyl methacrylate (HEMA, 35 wt%) or glyceryl methacrylate (GM, 35 wt%)) were examined by measuring the wall-to-wall contraction gap of a light activated resin composite in a cylindrical dentin cavity prepared in extracted human teeth. Among the tested bonding agents, only one material showed complete adaptation between the resin composite and the dentin cavity margin i. e. a dual cured agent that contained 10-methacryloxydecyl dihydrogen phosphate (MDP). The contraction gap of the intermediate resin was significantly reduced by pretreatment with the experimental self-etching dentin primers containing Phenyl P. PMID- 8004918 TI - Effects of the current used on determining a critical temperature by electrical resistivity measurements in dental alloys. AB - The electrical resistivity measurement to determine a critical temperature (Tc) in a stoichiometric CuAu alloy is discussed on the dependence of the current used. The temperature was measured on two ways: With the thermocouple connected to the specimen by spot-welding, and with them separated. In the latter case, the greater the current, the lower the apparent Tc because of the generation of Joule heat. To obtain a more precise Tc, the current should be as small as possible or the thermocouple should be located as close as possible to the specimen. It is highly desirable for the thermocouple and the specimen to be welded together, if the effects of some contamination can be ignored in measuring system. PMID- 8004919 TI - Castability and surface hardness of titanium cast plates obtained from experimental phosphate-bonded silica investment molds. AB - The effect of 12 different experimental compositions of phosphate-bonded SiO2 investments was examined on cast pure titanium. The mold temperature was 600 degrees C and the casting was conducted with an argon-arc melting and pressure casting machine. Castability was evaluated by the volume of casting porosity, which was calculated from the volume of wax pattern (15 mm x 15 mm x 1.5 mm), the weight of cast plate and the specific density of pure titanium. The existence of inner casting porosities was confirmed by an X-ray non-destructive inspection instrument. Cast plates made in molds with cristobalite had significantly lower castability and higher surface hardness than those in molds with quartz as a refractory material. Cast plates in molds (quartz-cristobalite mixtures) with 20% binder had lower surface hardness and fewer casting porosities than those in molds with 10% binder. PMID- 8004920 TI - Effect of casting methods on castability of pure titanium. AB - Two types of patterns were tested for castability: 1) polyester mesh pattern (20mm x 22mm with 100 open squares) and 2) 20mm x 20mm wax plates 1.0 and 1.5 mm in thickness. These materials were invested using a pre-arranged commercial phosphate-bonded investment for titanium. Three different types of casting machines were selected: 1) a pressure-type casting machine with separate melting and casting chambers, 2) a pressure-type casting machine with one chamber and 3) a centrifugal-type casting machine at 3000 rpm. Pure titanium (> 99.5%) was cast into the molds at a mold temperature of 100 degrees C. The castability of mesh pattern was evaluated in terms of the number of cast segment, and the cast plate was evaluated using X-ray transparent images by a digital imaging technique. The centrifugal casting method showed the best castability among these three casting methods. PMID- 8004921 TI - Effect of an ultraviolet light-activated coating material on reduction of the leaching of methyl methacrylate and formaldehyde from denture acrylic resins. AB - Effect of glazing with an ultraviolet light-activated coating material on reduction of the leaching of methyl methacrylate and formaldehyde from denture acrylic resins was quantitatively evaluated. Disks prepared from auto-polymerized resins were painted with the material and radiated with ultraviolet light. The disks were immersed in artificial saliva and the concentrations of methyl methacrylate and formaldehyde leached were determined by high-performance liquid chromatography and flow injection analysis. Compared to untreated controls, the glaze significantly decreased concentrations of both leachable substances. Treatment with an ultraviolet light-activated coating material is effective in suppressing the leaching of methyl methacrylate and formaldehyde from acrylic resins as well as in smoothing the denture surfaces. PMID- 8004922 TI - Tensile bond strength and curing gap formation of a dentin bonding resin. AB - Tensile bond strength and contraction gap tests were carried out using a new dentin bonding resin in association with various dentin conditioning and priming materials in vitro. For the tensile bond test, significant differences were found between the nonconditioned and conditioned dentin, and the primed and non-primed dentin surfaces. The strongest bond was obtained using a combination of phosphoric acid conditioning and priming with HEMA in glutaraldehyde at 151.3 kgf/cm2. Gap test results showed the presence of gaps in all of the test groups, but with variation in the extent of gap formation. A not significant, inverse correlation was determined between the tensile bond strength and gap tests (R = 0.65). The new bonding resin obtained good bond strengths in all cases, but high bond strengths can only be obtained with a combination of etching and priming. Similarly, the smallest gaps were associated with the etched and primed groups. PMID- 8004924 TI - Evaluation and treatment of urinary incontinence in the adult. PMID- 8004923 TI - Rational antidepressant selection. PMID- 8004925 TI - Critical life events and the onset of illness. AB - What can we conclude from these studies? One fact seems certain: there is no simple connection between life events and illness. Whether we get sick from an infection or a negative life experience depends on more than a germ or stress. All disease is multifactorial, and the resources that help protect us have much to do with our sense of support and control over our lives. What happens in our endocrine system and to our immune response is a function of what is going on inside our heads and hearts--the meanings we give to events and the feelings we have about them. Skeptics have long doubted these tenets. However, emerging evidence increasingly dispels these doubts and has replaced them with a biopsychosocial model based on psychoneuroimmunology (PNI). Indeed, Cousins described PNI as "the new science of medicine." To date, more than a dozen academic medical centers in the United States have PNI research programs and the list is growing. With expanded scientific study of the mind-body connection, people in general will come to recognize that whether they become ill is not always a matter of chance, but to a considerable extent something under their own control. PMID- 8004926 TI - Treatment of hepatitis B: current practice. PMID- 8004927 TI - Arthritis: it ain't necessarily so. PMID- 8004928 TI - Prevention and treatment of osteoporosis. PMID- 8004929 TI - Treatment of asymptomatic patients with left ventricular dysfunction. AB - Results of the SOLVD prevention trial and of the SAVE trial indicate that long term treatment with ACE inhibitors in asymptomatic patients with LV systolic dysfunction prevents the progression to overt CHF and reduces hospitalizations for CHF. ACE inhibitors have been shown to reduce mortality in at least some subsets of asymptomatic patients with LV systolic dysfunction, notably those with recent myocardial infarction. PMID- 8004931 TI - A lymphocyte colony assay for culture of sheep lymphocytes. AB - A procedure for culturing sheep peripheral blood lymphocytes in soft agar was standardized. The variables that were evaluated included the type of T lymphocyte mitogens, mitogen doses, cell number, distribution of the cells in the culture vessel and the duration of the culture. Both concanavalin A (CON A) and phytohemagglutinin A (PHA) stimulated the formation of lymphocyte colonies. However, CON A consistently produced more and larger colonies. The doses of CON A and PHA which yielded the maximum number of colonies were 35 and 61 micrograms/ml, respectively. The optimum number of cells per well as 1.36 x 10(6). Adherence of the cells to the floor of the culture vessel was required for the colonies to form. The maximum number of colonies was attained between day 5 and day 6 of culture. The lymphocyte colony assay may be a useful adjunct to other immunologic assays for studying cell-mediated immunity of sheep. PMID- 8004930 TI - Lymphocyte colony formation by aleukemic sheep infected with bovine leukemia virus. AB - The objective of this study was to investigate the effects of bovine leukemia virus (BLV) infection in sheep. A prospective study of the serologic, hematologic, and histologic changes of sheep infected with BLV was conducted. Antibodies to BLV were detectable in the sheep 3 weeks after exposure to blood from an infected cow and persisted during a 120 week examination period, whereas all control sheep remained seronegative. There were no statistically significant differences between the leucocyte counts, lymphocyte counts, and lymphocyte percentages of the infected and control sheep during the first 120 weeks of this study. However, one sheep did develop a leukopenia and lymphopenia 95 weeks after it became infected and died of histologically-confirmed lymphosarcoma 10 days later. A lymphocyte colony assay was used to study the effects of BLV infection on colony formation by sheep lymphocytes in vitro. There was no significant difference in the number of lymphocyte colonies formed by BLV infected and control sheep. Nor was there a significant difference in the number of colonies formed by lymphocytes from the BLV infected sheep, when the autologous sheep serum was replaced with either pooled serum from the infected sheep or with pooled serum from the control sheep. BLV infection in aleukemic sheep does not appear to have an adverse affect on colony formation by lymphocytes in vitro. PMID- 8004932 TI - Cell-mediated and humoral immunity in sheep exposed to bovine immunodeficiency like virus. AB - Six sheep were transfused intraperitoneally with whole blood from two sheep chronically infected with the bovine immunodeficiency-like virus (BIV). Five sheep were transfused intraperitoneally (i.p.) with normal ovine whole blood and served as controls. Five of six BIV-inoculated sheep seroconverted; four were transiently seropositive while one remained seropositive for the duration of the experiment. Tests for nonspecific lymphocyte reactivity to mitogens were performed monthly for one year. At approximately 10 months postinoculation, all sheep were immunized with chicken ovalbumin, canine red blood cells, and tuberculin. There were no significant associations between BIV exposure and deficits in antibody production to chicken ovalbumin and canine red blood cells; nonspecific lymphoproliferative responses to concanavalin-A, lipopolysaccharide, and pokeweed mitogen; specific lymphoproliferative responses to ovalbumin and tuberculin purified protein derivative; or cutaneous delayed type hypersensitivity to tuberculin purified protein derivative. Exposure to BIV did not alter the humoral or cell mediated immune responses of sheep in the first year of exposure. PMID- 8004933 TI - "Not proper mammals": immunity in monotremes and marsupials. AB - Immune systems and responses in Monotremata and Marsupialia are reviewed. The Monotremata (Prototheria) are egg-laying mammals. Few studies have been carried out on monotremes. The structure of the lymph nodules of Tachyglossus aculeatus is unusual, and the occurrence of IgG in this species is noteworthy: IgG has not yet been found in any non-mammal. A number of Marsupialia (Metatheria) species have been used as immunological models. Generally immune responses are somewhat slower and less accentuated than in placental (eutherian) mammals. Of interest is the presence of cervical and thoracic thymuses in several marsupials. Marsupials are born very immature and possess rather rudimentary immune responses at birth: the neonate may provide a helpful model for immune ontogenesis. Marsupials have a full repertoire of immunoglobulin classes. MHC Class II (but not Class I) gene polymorphism may be limited. Studies using molecular biology techniques are awaited to elucidate the structural organization of the immune components and to determine similarities and differences between marsupials' and other animals' immune systems. PMID- 8004935 TI - Detection of potential virulence markers of Vibrio vulnificus strains isolated from fish in Sweden. AB - A variety of potential virulence markers such as the production of cytotoxin, haemolysin, exoenzymes, bactericidal action of sera, presence of capsule and adhesion to human intestinal cells were investigated on Vibrio vulnificus strains isolated from eels in Sweden. The strains had the capacity of producing all or some of the above-mentioned virulence markers, to varying degrees though none of the strains produced any capsule. The strains also bound specifically to human intestinal cells in vitro with maximum adhesion levels of 30 bacteria/cell. The results on binding of V. vulnificus cytotoxin to HeLa cells, showed that a very short exposure time (30 min) was required for inducing the cytotoxic effects. V. vulnificus is a relatively new addition to the list of bacteria pathogenic for humans, and since there are increasing reports on its isolation from aquatic environments and seafood (e.g. raw oysters, crabs and shellfish), the results on virulence profiles of V. vulnificus strains presented above emphasize the importance of these organisms in public health and epidemiological studies. PMID- 8004934 TI - Long term in vitro growth of lymphoblastoid cells in the dog. AB - Attempts to grow in vitro cells from canine lymphoid organs led to observation of the occurrence of a spontaneous, delayed and transitory growth of cells in suspension in two lymphoma cultures (out of 20) but also from one (out of 20) dog with unrelated disorder. These cells, with a lymphoblastoid cytological appearance, lack detectable immunoglobulins in cases studied originating from lymphomatous dogs, and have a pseudodiploid canine karyotype. Neither appearing fully immortalized nor showing any tumorigenicity in nude mice or immunosuppressed newborn rats, these may be of lymphoblastoid nature, rather than arising from some tumorous cells. The mechanisms that have triggered the cell growth are still unknown, but such cells could remind of human lymphoblastoid cells, associated with lymphotrophic viruses, still unknown in the dog. PMID- 8004936 TI - The role of sialic acid and Ca2+ ions in rabies virus-infected foxes brain. AB - The receptors for rabies virus on the neuron membranes are polysialogangliosides arranged in multicomponent gelate structures. The impulse conductivity at the synapse membranes also depends on the interactions between negatively charged sialic acid from the oligosaccharide parts of gangliosides and positively charged Ca ions. From individual brain regions of healthy foxes and foxes naturally infected with rabies virus glycolipoprotein preparations were isolated. In them, the presence of polysialogangliosides and the concentration of sialic acid, Ca ions, and proteins were evidenced. The concentration of sialic acid was increased in all tested brain regions of the infected foxes. In the preparations from the cortex cerebri or cornu Ammonis of the infected foxes, 20-fold higher levels of sialic acid and the decreased concentrations of Ca ions were recorded. The increase in sialic acid levels is directly responsible for the augmented negative charge at synaptic membranes and, consequently, for a much higher permeability of these membranes, which results in a persistent stimulation followed by the release of neuro-transmitters. PMID- 8004937 TI - Decline in the phagocytic function of alveolar macrophages from mice exposed to cigarette smoke. AB - An investigation was made of the effects of a short and acute exposure to cigarette smoke on the capacity of alveolar macrophages from mice to carry out all stages of the phagocytic process. Cigarettes were commercial 80 mm filter cigarettes that contained 17 mg of tar and 1.1 mg of nicotine per cigarette. The acute exposure of each animal was with one cigarette for 15 min (until the complete consumption of the cigarette) in a box-shaped plastic chamber, 7732 cm3 vol and 450 cm2 floor surface, with a 3 cm dia airhole. Animals were sacrificed immediately after the exposure to the smoke. The results showed no differences either in the adherence or in the chemotaxis capacities between alveolar macrophages from control mice and from mice exposed to cigarette smoke. However, there was a significant decline both in attachment capacity and in ingestion capacity for Candida albicans. The reason for this was a decline in the number of macrophages with phagocytic capacity (percent of phagocytosis) and in the number of C. albicans phagocytized per cell (phagocytic efficiency). The conclusion is that a short, acute exposure to a smoke-filled atmosphere induced a decrease in the phagocytic function of alveolar macrophages. PMID- 8004938 TI - A microcomputer program for the design and analysis of phase II cancer clinical trials with two group sequential methods, the sequential probability ratio test, and the triangular test. AB - We developed an interactive and menu-driven computer program to help investigators design and analyze phase II cancer clinical trials with a group sequential method, namely the sequential probability ratio test or the triangular test. Based on the values selected for the parameters of the trial, the "Design" option allows one to obtain, using simulations, the statistical properties (type I and II error rates and the probability that the test accepts the hypothesis of inefficacy under 21 different assumptions) and the average sample size (under the same assumptions) of the selected test. The "Analysis" option (i) computes, at each analysis, the two statistics V and Z on which the sequential method is based and plots the sample path from the number of successes observed, and (ii), using asymptotic properties, gives the significance level of the test and a point estimate (with its 95% confidence interval) of the parameter of interest at the last analysis. PMID- 8004939 TI - A computer system for skeletal growth measurement. AB - In this paper, we have presented a new image-processing system for the measurement of skeletal growth in pediatric radiology. From a standard posterior and anterior view radiograph, taken from a left hand, the proposed system first automatically locates the phalangeal region of interest, and then measures the geometrical parameters associated with skeletal maturity. Finally, the bone age is estimated by using the standard phalangeal length table. Clinical studies reveal that the computer processing has resulted in an objective and accurate assessment of skeletal age. It greatly improves the shortcomings, including inter and intraobserver variations and inaccuracy, reported in other research by manual methods. In conclusion, it is an inexpensive and useful tool for the evaluation of short-term abnormalities in the skeletal growth of children. PMID- 8004940 TI - An interactive computer model of propagated activation with analytically defined geometry of ventricles. AB - A computer model of propagated activation in cardiac ventricles was developed for simulation experiments in an interactive regime on personal computers. In the model, the geometry of ventricles is defined by parts of "compound quasi ellipsoids". The parameters specifying these ellipsoids as well as their spatial positions are derived from input data characterizing the heart geometry. Because the ventricles are defined analytically, the model renders a wide range of possibilities to vary their shape and gross dimensions. The activation is propagated from predetermined starting elements in agreement with Huygen's principle. Different propagation velocities for the myocardium and the subendocardial mesh of Purkinje fibers also may be simulated. The results of computer simulations may be evaluated both qualitatively, by isochrones of the activation propagation, and quantitatively, by the resulting cardiac vector computer in any moment of activation process. PMID- 8004941 TI - Segmentation of intensity basins in gray-scale images. AB - An algorithm to detect intensity basins in gray-scale images is described. An image is modeled as a topographical surface and illuminated by multiple light sources to form shadows in the intensity basins of the surface. A segmentation is then obtained by detecting regions of shadow. Experimental results for a sample skin image are presented. PMID- 8004942 TI - Automatic detection of wave boundaries in multilead ECG signals: validation with the CSE database. AB - This paper presents an algorithm for automatically locating the waveform boundaries (the onsets and ends of P, QRS, and T waves) in multilead ECG signals (the 12 standard leads and the orthogonal XYZ leads). Given these locations, features of clinical importance (such as the RR interval, the PQ interval, the QRS duration, the ST segment, and the QT interval) may be measured readily. First, a multilead QRS detector locates each beat, using a differentiated and low pass filtered ECG signal as input. Next, the waveform boundaries are located in each lead. The leads in which the detected electrical activity is of longest duration are used for the final determination of the waveform boundaries. The performance of our algorithm has been evaluated using the CSE multilead measurement database. In comparison with other algorithms tested by the CSE, our algorithm achieves better agreement with manual measurements of the T-wave end and of interval values, while its measurements of other waveform boundaries are within the range of the algorithm and manual measurements obtained by the CSE. PMID- 8004943 TI - A system for the on-line acquisition, visualization, and analysis of pressure area loops. AB - Transesophageal echocardiography is a widely accepted technique for the assessment of left ventricular (LV) function in the operating room, intensive care unit, and cardiac catheterization suite. Not only do the images generated by these systems provide the observer with dynamic views of currently ongoing cardiac mechanics, but the computed LV area values obtained by the automated border detection system can be converted to an analog signal and then used to generate pressure-area loops if LV pressure is measured simultaneously. The intraventricular area has been shown to correlate closely with intraventricular volume and to vary proportionately. Therefore, it can be substituted for volume to generate pressure-area loops that display equivalent behavior to external perturbations as pressure-volume loops. Visualization of these waveforms and the values extracted from them, along with the associated hemodynamic values, provide valuable insight into ventricular function and heart-lung interactions. This paper describes a system that was designed and developed to acquire, display, store, and analyze pressure-area loops in addition to other associated hemodynamic signals of interest. PMID- 8004944 TI - A PC-based generator of surface ECG potentials for computer electrocardiograph testing. AB - The system is composed of an electronic circuit, connected to a PC, whose outputs, starting from ECGs digitally collected by commercial interpretative electrocardiographs, simulate virtual patients' limb and chest electrode potentials. Appropriate software manages the D/A conversion and lines up the original short-term signal in a ring buffer to generate continuous ECG traces. The device also permits the addition of artifacts and/or baseline wanders/shifts on each lead separately. The system has been accurately tested and statistical indexes have been computed to quantify the reproduction accuracy analyzing, in the generated signal, both the errors induced on the fiducial point measurements and the capability to retain the diagnostic significance. The device integrated with an annotated ECG data base constitutes a reliable and powerful system to be used in the quality assurance testing of computer electrocardiographs. PMID- 8004945 TI - Albert Schweitzer's simple philosophy. PMID- 8004946 TI - Malabsorption of thyroid hormone with cholestyramine administration. PMID- 8004947 TI - Outcome measurements are long overdue. PMID- 8004948 TI - Durable medical equipment. PMID- 8004949 TI - Stereotactic needle biopsy of nonpalpable breast masses. AB - One hundred two patients with nonpalpable breast masses that presented as mammographic densities with or without calcification were studied consecutively. Using the Stereotix stereotactic device, fine-needle aspirations were obtained with subsequent hook-wire placement followed by surgical excision. Pathology results were reached separately and then compared to the cytologic diagnoses. For patients with adequate cytologic material, sensitivity was 95% and specificity was 100%. There were six suspicious or equivocal diagnoses: three were determined to be benign, while three were malignant. There was inadequate tissue in 13%. Although this technique had limitations, for patients with adequate cytologic and histologic material the accuracy was excellent. PMID- 8004950 TI - Adolescent contraceptive counseling and gynecology: a deficiency in pediatric office-based care. AB - With the large and increasing numbers of sexually active adolescents, pediatricians must learn to deal with the issues of adolescent pregnancy and sexually transmitted diseases (STD). This is particularly true at a time when health care reform will encourage primary care physicians to assume a greater role in general medical management of their patients. One hundred Connecticut general practice pediatricians were randomly selected to examine the frequency, level of comfort, and rationale for involvement regarding sexual history taking, contraceptive counseling, and performance of pelvic examinations. This represents 9% of all Connecticut pediatricians. The response rate was 54%. The results were as follows: Seventy-nine percent of responding pediatricians counseled on STDs, 39% counseled on family planning, and only 62% almost always took a sexual history from the their adolescent patients, ages 10 and up. Thirty-one percent of respondents stated they would refer a male inquiring about contraception to a family planning clinic. Thirty-eight percent never do pelvic examinations on their sexually active adolescent patients. Connecticut pediatricians are providing adolescents with counseling on other high-risk behaviors such as drug and alcohol use, but provide inadequate care related to adolescent sexual activity. PMID- 8004951 TI - Untended social problems add to cost of health care in Connecticut. PMID- 8004952 TI - Dealing with disciplinary hearings before Connecticut's Department of Health Services (the true story). PMID- 8004953 TI - The contractile apparatus of podocytes is arranged to counteract GBM expansion. PMID- 8004954 TI - Structural differentiation of endothelial basement membrane in the kidney vasculature. PMID- 8004955 TI - Oncogenes control stromelysin and collagenase gene expression. PMID- 8004956 TI - Tissue inhibitors of metalloproteinases: role in tumor progression. PMID- 8004957 TI - A one-step sandwich enzyme immunoassay for tissue inhibitor of metalloproteinases 2. PMID- 8004958 TI - Glomerulosclerosis: studies of its pathogenesis in humans and animals. PMID- 8004959 TI - The contribution of mesangial cell collagen synthesis to the pathogenesis of diabetic nephropathy. PMID- 8004960 TI - Transforming growth factor-beta and extracellular matrix deposition in the kidney. PMID- 8004961 TI - Effects of low-protein diet on mRNA for ECM components, MMPs and TIMPs in glomeruli of focal glomerular sclerosis. PMID- 8004962 TI - Is mesangial cell proliferation required for extracellular matrix expansion in glomerular disease? PMID- 8004963 TI - Structure and organization of type IV collagen of renal glomerular basement membrane. PMID- 8004964 TI - Insulin-like growth factor-I receptor in metanephric development. PMID- 8004965 TI - Heparan sulfate proteoglycans in the human sclerosing and scarring kidney. Changes in heparan sulfate moiety. PMID- 8004966 TI - Interactions between tubulointerstitial nephritis antigen and laminin or type IV collagen. PMID- 8004967 TI - Anti-type IV collagen antibodies in Goodpasture syndrome. PMID- 8004968 TI - Nephropathy in HIV-transgenic mice. PMID- 8004969 TI - Introduction of a foreign gene into the kidney in vivo: development of glomerulosclerosis by the transfection of genes for PDGF and TGF-beta. PMID- 8004970 TI - Ultrastructural architecture of basement membranes. PMID- 8004971 TI - The chain composition of aorta basement membrane collagen IV, localization of the chains in aorta and supramolecular assembly of the collagen IV protomers. PMID- 8004972 TI - Isolation and characterization of human cDNAs and genomic DNAs encoding alpha 4(IV) and alpha-6(IV) chains reveal the presence of a distinct subclass of collagen IV genes. PMID- 8004973 TI - Molecular organization and gene regulation of type IV collagen. PMID- 8004974 TI - Laminin self-assembly: a three-arm interaction hypothesis for the formation of a network in basement membranes. PMID- 8004975 TI - Structure, molecular assembly and tissue distribution of FACIT collagen molecules. PMID- 8004976 TI - Further characterization of basement membrane-associated collagen in comparison with type IV collagen alpha-1-chain in the extracts of human placenta with monoclonal antibodies. PMID- 8004977 TI - Functional significance of NC1 containing alpha-3-chains of type IV collagen. PMID- 8004978 TI - Matrix metalloproteinases. A mini-review. PMID- 8004980 TI - Handedness as a function of twinning, age and sex. AB - Questions about twin birth, sex, age and handedness for writing were asked as part of a survey of hearing disability (Davis, 1989) in a large sample of the adult population. The findings show unequivocally that the prevalence of left handedness is higher in twins than in the singleborn, in males than in females and in younger than in older adults. There was a marked and regular decline in the percentage of left writers with increasing age, but the effects for twinning and sex were evident in all of 7 age bands from 18 years to 80+. The findings are consistent with the assumption of the right shift theory of handedness (Annett, 1972, 1985) that the rs+ gene is expressed more strongly in females than in males, and in the singleborn than in twins. PMID- 8004979 TI - Metalloproteinase expression and hormonal regulation during tissue remodeling in the cycling human endometrium. PMID- 8004981 TI - Explicit memory, procedural learning and lexical priming in Alzheimer's disease. AB - Different aspects of memory functions were studied in two groups of patients with Alzheimer's disease (AD) and in normal elderly controls. The tests included: explicit memory tests with free and cued recall, and recognition measures; learning of a motor skill; learning of a perceptual skill with verbal material; a priming task with the word stem completion paradigm. The data confirmed that, besides severe impairment for all measures of explicit memory, AD patients were able to learn and retain normally a motor skill in the rotor pursuit task, even across a long retention interval. Moreover, sparing of procedural learning was not restricted to motor tasks, since patients learned normally a mirror-reading task, demonstrating (a) rapid acquisition of the procedure, and (b) acquisition of item-specific information for repeated words. This last effect is accounted for in terms of repetition priming effects rather than of explicit memory strategies, since patients had also normal repetition effect in the word stem completion paradigm. PMID- 8004982 TI - Frequency judgments for semantic categories in amnesics and normal controls. AB - Korsakoff's amnesics and normal controls read descriptions of five famous and five unknown individuals. Each individual was linked with five exemplars of one semantic category and three of another. Subjects decided which of the two relevant categories had been linked more frequently with each individual and made recognition judgments with respect to the exemplars. An analysis of the relationship between recognition and frequency judgment performance suggested that the normals but not the amnesics had used explicit memory for the exemplars in making their frequency judgments. An analysis of frequency judgment performance suggested that the judgments of the amnesics but not the normals reflected implicit memory for the associations between the individuals and the categories that had been used to describe them. PMID- 8004983 TI - Covert processing of information in hemianesthesia: a case report. AB - A 69-year-old patient with a cortical lesion of the primary sensory area showed a surprising sensorimotor control of the anesthetized arm. This observation suggested the existence of residual capacities of somesthetic information processing. This hypothesis was tested using a forced choice procedure on four tasks involving discrimination between different characteristics of the tactual kinaesthetic stimulus. Whereas the patient was unable to identify the direction of movement or to discriminate between different letters, she could detect the occurrence of the stimulation or its dynamic quality significantly well. These results are discussed in reference to an anatomo-functional organization analogous to the one underlying the processing of visual information. PMID- 8004984 TI - Integrative agnosia following progressive multifocal leukoencephalopathy. AB - A 43 year-old man with presumed progressive multifocal leukoencephalopathy developed difficulty recognizing objects and faces in the presence of adequate visual acuity and visual fields. His copying and matching of line drawings was intact, suggesting that his agnosia was associative. However, he had difficulty perceiving overlapping forms and drawings of single objects as integrated wholes. Unlike control subjects, he made fewer errors identifying silhouettes compared to line drawings with internal details. These alterations, together with his feature by-feature descriptions of objects and copying, suggest that his agnosia was due to a disturbance in integrating local form features, as described by Riddoch and Humphreys (1987). This interpretation is supported by the findings that his tactile recognition and semantic and structural knowledge of the objects he could not identify visually were intact. Furthermore, his deficient performance in categorical matching of photographs to objects was dependent upon the perceptual complexity of the photographs. Similar deficits in early form processing described by other investigators are discussed. PMID- 8004985 TI - Dual task performance in amnesic and normal people: does resource depletion cause amnesia? AB - Normal peoples' memory can be seriously disrupted if their cognitive resources are depleted by means of an experimental manipulation (such as distraction at encoding or at retrieval). By analogy, it has also been suggested that amnesia might result directly from pathological loss of cognitive capacity. This hypothesis was examined in 12 mixed amnesics and 12 normal people by means of a 'dual task' study. It was argued that if amnesics have reduced cognitive resources they should be disproportionately impaired in dual task performance relative to single task performance and in comparison to controls. This result was unambiguously demonstrated using a visual (letter detection) task combined with an auditory (semantic decision) task. However, correlations with measures of frontal function and with indicants of severity of amnesia proved insignificant and so the role of resource depletion in amnesia remains, as yet, unproven. PMID- 8004986 TI - A case of ideational apraxia with impairment of object use and preservation of object pantomime. AB - A case of tool use disturbance without impairment of motor skills and of conceptual knowledge of how tool must be used is reported. The patient could not manipulate objects isolatedly or in succession but could pantomime their use on command and on imitation. This finding suggests that manipulation of objects may dissociate from pantomime without objects. We interpret this syndrome as a results of mismatch of tool and tool use. PMID- 8004987 TI - The neglected page. AB - Normal subjects bisect vertical lines above the true midpoint. We posited that the portion of the page farthest from the line or the page's geometric center, though not the focus of attention, would still engage attention. Therefore, subjects should make bisection errors in the direction of the distant portion or geometric center. We expected the greatest superior bisection errors to be made when lines were placed at the bottom of the page and the smallest errors to be made when the lines were placed at the top of the page. Ten young, normal subjects bisected vertical lines placed in 1 of 3 positions on a page (top, center, bottom) with the page located in 1 of 3 spatial locations (superior, middle, inferior). The results of our study were consistent with our predictions. Thus, although the page on which a line is bisected is often ignored, it is not neglected. PMID- 8004988 TI - Spared and impaired cognitive abilities after bilateral frontal damage. AB - We report on a patient (PG) with a severe behavioural disorder following massive bilateral prefrontal damage due to herpetic encephalitis. The lesion involves also the mesial and polar regions of the temporal lobes; the frontal dorso lateral cortices were relatively spared. The patient's inattentiveness and alternating impulsive and apathetic behaviour led to her social alienation. The only self-motivated activities we observed were those initiated to satisfy her enhanced urge to eat and play games. She did not react to surprise stimuli that consistently elicit a reaction of surprise in healthy people. She also presented "adynamic aphasia" associated with anomia and episodic amnesia. A striking feature of the syndrome was the patient's consistent "utilization behaviour". Her motor behaviour was marked by constant akathisia. She performed surprisingly well on intelligence, "frontal", and visuo-spatial tests. This non-demented patient exhibited a clear dissociation between her relatively spared cognitive abilities and grossly impaired behaviour. In the discussion we explore the extent to which a defect of the supervisory control may be held responsible for the inconsistencies in the patient's coping skill performances. PMID- 8004990 TI - New-association priming of word identification in normal and amnesic subjects. AB - Subjects took an implicit memory test in which pairs of unrelated words were flashed briefly and the ability to identify the second word of each pair was measured as a function of prior study. In young subjects, identification was better when the second word had been studied compared to when it had not been studied (word-specific priming). Identification was also better when the two words had been paired at study compared to when they had been studied separately (association-specific priming). In amnesic patients, word-specific priming was normal compared to that in age- and IQ-matched control subjects. Association specific priming was observed, but it was below normal levels. This outcome suggests that the amnesic dysfunction can encompass priming of new verbal associations but spare priming of existing verbal information. PMID- 8004989 TI - Are semantic systems separately represented in the brain? The case of living category impairment. AB - Following herpes encephalitis, a patient showed impaired knowledge of animals, fruits and vegetables, flowers and food (so called living things categories), whatever the modality in which stimuli were presented and responses were given. A series of experiments showed that the deficit specifically affected the ability to retrieve the perceptual features of the living stimuli defining their shape, while knowledge of their functional-encyclopedic properties was preserved. The patient had no problems with man-made objects, except when the recall of their colour, or the identification of their sound was requested. It is argued that the retrieval of the perceptual features was potentially disrupted for every type of category, but that the block was compensated for man-made objects, because the close correspondence between shape and function that characterises them provided an alternative route to access their structured form representations. On this account, the selective deficit for living categories seems contingent on the interaction between an overall cognitive impairment--the deficit in retrieving perceptual features--and some intrinsic properties of the stimulus--the factors that have modelled its form--and cannot be taken as evidence that semantic systems are allotted to separate cerebral areas. PMID- 8004991 TI - Dissociations among structural-perceptual, lexical-semantic, and event-fact memory systems in Alzheimer, amnesic, and normal subjects. AB - Patients with Alzheimer's disease (AD), patients with global amnesia (AMN), and normal control (NC) subjects received tests of recall and recognition, word completion priming, and incomplete-picture priming. The AD and AMN patients had impaired recall and recognition. The AD patients, but not the AMN patients, had impaired word-completion priming. In contrast, the AD patients had intact incomplete-picture priming, a form of priming shown to be perceptual in normal subjects. These results provide neuropsychological evidence for a dissociation between two components of repetition priming, perceptual priming as measured with identification tasks and nonperceptual priming as measured with generation tasks. Preserved perceptual priming in AD may be mediated by the occipital regions that are relatively spared in AD; compromised nonperceptual priming may be mediated by temporal regions that show dense neuropathological changes early in AD. PMID- 8004993 TI - Proteoglycan content in fresh and cryopreserved porcine aortic tissue. AB - Quantitative analysis of proteoglycans (PGs) revealed that the content of PG material from cryopreserved aorta, measured as uronate-positive material, was similar to that from fresh tissue (440 +/- 30 versus 430 +/- 7 micrograms/g wet tissue). Gel permeation column chromatography studies suggested that three PG fractions from cryopreserved tissue had molecular weights similar to PG fractions from fresh tissue; K(av) = 0.13, 0.47 (I), 0.20 (II), and 0.43 (III) from cryopreserved tissue and K(av) = 0.13, 0.50 (I), 0.23 (II), and 0.40 (III) from fresh tissue. Sequential extraction of tissue with guanidine-HCl (Gdn-HCl) followed by digestions with collagenase, elastase, and papain also demonstrated that there was no difference between fresh and cryopreserved tissues in the distribution of PGs in the extracts. Transmission electron microscopy analysis revealed less densely packed collagen fibers in cryopreserved tissues compared to fresh tissues. These studies indicate that there is no significant alteration in the content, molecular size, or distribution of PGs in properly cryopreserved tissue. PMID- 8004992 TI - Patterns of ice formation in normal and malignant breast tissue. AB - Normal and malignant human breast tissues were obtained from resection surgery and frozen on a directional solidification stage with controlled and uniform cooling rates. The frozen samples were freeze substituted and examined with a light microscope. It was observed that in both normal and malignant tissue, ice forms first in the connective tissue. The ice propagates along the connective tissue, which surrounds fat cells in normal adipose tissue and clumps of tightly packed malignant cells in the diseased tissue. This mode of freezing affects the osmotic response of malignant cells, causing intracellular ice crystal formation at unusually low cooling rates. PMID- 8004994 TI - Microcalorimetric study on myocardial metabolism in a hibernator and two nonhibernators at 20 degrees C and 37 degrees C. AB - Metabolic activity in cardiac tissue slices from the guinea pig (GP), the rat (RT), the nonhibernating summer and winter hedgehog (SH and WH), respectively, was determined at 20 degrees and at 37 degrees C from their rates of heat production, P, (units, W/g tissue) by direct and indirect calorimetry. Energy linked transport of Na+ and K+ in the tissues was determined from changes in metabolic rate induced by specific inhibition of the Na/K pump, the functional expression of Na/K-ATPase, the pacemaker enzyme in energy production assigned the role of transporting Na+ and K+ out of and into the cell. The results indicate a higher rate of energy production and utilization in the cardiac tissue of the hedgehog than in that of the nonhibernators, the rat and the guinea pig, at both temperatures. At 37 degrees C the rate at which the cardiac tissue from the hedgehog consumed oxygen was as much as six times that registered for the guinea pig. The temperature coefficients of P and of the Na/K pump in the tissues from the two groups of hedgehogs were significantly higher than in the tissues from the rat and the guinea-pig (P < 0.001). The determined metabolic indices, the basal rate of heat production P, the rate of oxygen consumption, P(O2) in thermal units (W/g tissue), and the Na/K-pump capacity (PC) indicate species-specific differences between the animals. Both PC and its variation with temperature, delta PC/delta T(o)C, were in the order WH > SH > RT > GP. These results indicate that the hedgehog's cardiac tissue, in comparison with that of the nonhibernators, has a greater capacity to generate energy in general and for active transport of Na+ and K+ at 37 degrees C after exposure to a lower temperature. A role is suggested for the Na/K-ATPase and some other unique rate limiting enzymes in the metabolic pathway for the observed differences in temperature tolerance and cardiac performance between hibernators and nonhibernators. PMID- 8004995 TI - Endothelial cell toxicity of preservation solutions: comparison of endothelial cells of different origin and dependence on growth state. AB - Previously, we have shown that cultured liver endothelial cells are affected by an energy-dependent injury when incubated in cold University of Wisconsin (UW) or histidine-tryptophan-ketoglutarate solution. Here, we studied the susceptibility of other endothelial cells to this type of injury. Aortic endothelial cells in early-confluent, i.e., still proliferating, monolayer cultures were damaged more quickly during cold incubation in UW solution than during cold incubation in Krebs-Henseleit buffer. At this stage the addition of KCN did not alter the loss of viability in UW solution, but when the culture period was prolonged, cells were protected by the addition of cyanide. A paradoxical, protective effect of KCN could also be observed in late-confluent, i.e., nonproliferating, cultures of coronary endothelial cells incubated in UW solution. Similarly, liver endothelial cells in subconfluent, growing cultures were damaged by the addition of cyanide (loss of viability after 48 h, 3 +/- 1% in UW, 65 +/- 19% in UW + KCN), whereas in late-confluent cultures the addition of cyanide to UW solution was protective (loss of viability after 48 h, 100 +/- 0% in UW, 31 +/- 15% in UW + KCN). Variations of culture period and seeding density and the use of inhibitors of cell proliferation demonstrated that liver endothelial cells acquire their susceptibility to energy-dependent injury along with confluence. Subcultured cells retained this susceptibility for some hours. These results suggest that the energy-dependent injury described previously is not confined to liver endothelial cells and that the occurrence of energy-dependent injury requires a capacity of the cells that develops only after cultures have grown to confluence. PMID- 8004996 TI - Differential osmotic behavior of mammalian oocytes before and after maturation: a quantitative analysis using goat oocytes as a model. AB - This study shows that immature and mature goat oocytes respond differently to hyperosmotic stress; when exposed to a 1.5 M propanediol solution, immature oocytes manifest a higher osmotic stress than do mature oocytes. This is the consequence of both higher water permeability (133.9 +/- 15.2 vs 82.4 +/- 4.4 x 10(-3) cm/min) and lower propanediol permeability (0.87 +/- 0.03 vs 1.20 +/- 0.03 x 10(-3) cm/min at 20 degrees C) in the immature than in the mature stage. The difference of osmotic behavior between these two types of oocytes is abolished following exposure to cytochalasin D, a drug known to modify the cellular microfilament network. This result suggests differences in actin organization between the two types of oocyte, probably at the cortical level. Calculated values of the intracellular concentration of propanediol as a function of time of exposure show that propanediol rapidly permeates both types of oocyte and that the kinetics of intracellular concentration are lowered by cytochalasin treatment. PMID- 8004997 TI - Straw thermal stabilizer for embryo cryopreservation. AB - Embryo cryopreservation procedures have been highly developed to support in vitro fertilization techniques, but the clinical results have not met initial expectations. Many variables influence the outcome of the embryo cryopreservation procedure. Exposure to classical freezing media does not affect further embryo development. Therefore, the first crucial step seems to be embryo thermal behavior during the freezing/thawing procedure. With the aim of avoiding thermal oscillations to the embryos due to liquid nitrogen injection into the freezing chamber, we have developed a straw thermal stabilizer (STS) cryopreservation accessory that when adapted to a programmable biological freezer offers a more exact control of the straws temperature and also a greater reproducibility of the freezing process. The STS incorporates a seeding mechanism controlled by specially designed software. For the biological assays, 2-cell mouse embryos were cooled until seeding at -7 degrees C or frozen to -120 degrees C using 1.5 M 1,2 propanediol and 0.1 M sucrose. As control groups, embryos were either untreated or were exposed to cryoprotectants, developing to blastocyst at rates of 90.8 and 88.4%, respectively. The embryos cooled until seedling or subjected to the complete freezing procedure developed into blastocysts at rates of 95.7 and 82.8%, respectively, disregarding the effect of the cryoprotectant exposure. These results show a substantial improvement in cryopreservation with no loss in embryo development due to the seeding procedure. PMID- 8004998 TI - Effect of antifreeze proteins on the motility of ram spermatozoa. AB - The effect of the antifreeze peptide type I (AFP) from Winter flounder, Pseudopleuronectes americanus, and the antifreeze glycoprotein (AFGP) from Antarctic cod, Dissostichus mawsoni, was assessed on the motility of ram spermatozoa (Dorset and Dorset x Romney) after chilling (5 degrees C) and after freeze-thawing. During chilling, spermatozoal motility decreased significantly at an AFP or AFGP concentration of 0.1 microgram/ml and at concentrations above 10 micrograms/ml (P < 0.05). Thus, at 5 degrees C these antifreeze proteins can have a mildly cytotoxic effect at certain concentrations. Addition of AFP or AFGP to the freezing medium at concentrations of 0.1 to 10 micrograms/ml significantly reduced the loss in spermatozoal motility that occurs due to the freeze-thaw process (P < 0.001). The effect was not concentration dependent nor did it depend on which antifreeze protein was added. However, due to the cytotoxicity during the chilling stage, only AFP at a concentration of 10 micrograms/ml increased the percentage of motile spermatozoa significantly following freezing and thawing over that of the control (P < 0.05). Mechanisms to explain the effect of these proteins on spermatozoal motility after chilling and after freeze-thawing are proposed. PMID- 8004999 TI - Antifreeze glycoproteins from antarctic notothenioid fishes fail to protect the rat cardiac explant during hypothermic and freezing preservation. AB - The antarctic notothenioid fishes avoid freezing through the action of circulating antifreeze glycoproteins (AFGPs). This study investigated whether AFGPs could serve as cryoprotectants for the isolated rat heart under three different storage conditions. (1) Hearts were flushed with 15 mg AFGP/ml cardioplegic solution (CP) and stored for 9 h at 0 degrees C. This AFGP concentration has been reported to protect pig oocytes during hypothermic storage. (2) Hearts were flushed with 10 mg AFGP/ml CP-14 and stored frozen at 1.4 degrees C for 3 h. At this concentration the AFGPs significantly reduce the solution freezing point and also change the crystal morphology from dendritic to spicular. (3) Hearts were flushed with 10 micrograms AFGP/ml CP-15 and stored frozen at -1.4 degrees C for 5 h. At this low concentration the AFGPs have a strong inhibitory effect on ice recrystallization, but have little effect on the freezing point and less apparent effect on the crystal habit. After hypothermic or freezing storage, the functional viability was assessed by determining cardiac output (CO) during working reperfusion. No difference in CO was found between AFGP-treated and untreated hearts after 9 h of 0 degree C storage. CO in hearts frozen in CP-14 without AFGPs recovered to 50% of the freshly perfused control hearts. Hearts frozen in the presence of high concentrations of AFGPs (10 mg/ml CP-14) failed to beat upon thawing and reperfusion, although their tissue ice content was less than that found in hearts without AFGP treatment.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8005000 TI - Cryoprotection of yeast by alcohols during rapid freezing. AB - We have investigated the cryoprotective effect of alcohols on Saccharomyces cerevisiae and other yeast under various freezing conditions. For S. cerevisiae, at a cooling rate of 3 degrees C min-1 methanol and ethanol acted as cryosensitizers. However, at a cooling rate of 200 degrees C min-1, both methanol and ethanol proved superior to all other cryoprotectants tested, including glycerol, dimethyl sulfoxide, lactose, trehalose, polyethylene glycol, and polyvinyl pyrrolidone. Propan-2-ol also demonstrated a small but measurable effect although propan-1-ol and butan-1-ol demonstrated no cryoprotective effect. A minimum cooling rate of 25 degrees C min-1 to elicit the cryoprotective effect of ethanol was necessary; below this rate it acted as a cryosensitizer. At cooling rates up to 650 degrees C min-1 substantial cryoprotective effect was still evident. Although the effect of ethanol was variable for other yeast genera tested, ethanol acted positively for all strains of S. cerevisiae. We hypothesize that the cryoprotective effect of alcohols during rapid cooling is a result of their ability to induce increased membrane permeability, allowing rapid water equilibration during extracellular freezing and avoidance of intracellular ice crystal formation. PMID- 8005001 TI - Chemoprevention of cancer. AB - Chemoprevention is a strategy used to block the development of cancers in human beings. This emerging field has broad potential for influencing cancer incidence rates in defined high-risk groups and the general population. In this review, we define some of the mechanisms of carcinogenesis, describe some of the genetic markers of carcinogenesis, and list possible biomarkers that may serve as surrogate end points in chemoprevention studies. A major component of this review is a description of the agents that are currently under investigation in animal systems or in human trials. They are grouped according to the agents that block or suppress mutation, such as oltipraz, selenium, vitamin C and the flavones, or according to agents that block promotion and proliferation, such as difluoromethylornithine, tamoxifen, nonsteroidal antiinflammatory drugs, and the vitamin A derivatives. We describe the issues that are considered in the design of chemoprevention trials and in the phase I, II, and III components of these trials. The following national trials are discussed: the Breast Cancer Prevention Trial, which uses tamoxifen; the Prostate Cancer Prevention Trial, which uses finasteride; and a Lung Cancer Prevention Trial, which uses 13-cis-retinoic acid. The review ends with some insights about future studies in chemoprevention. PMID- 8005002 TI - Effect of Bacillus thuringiensis beta exotoxin on ultrastructures of midgut cells of Culex sitiens. AB - In midgut cells of Culex sitiens intoxicated with beta exotoxin of Bacillus thuringiensis, the microvilli are greatly reduced. In the cytoplasm there is progressive disarrangement of the membranes of the rough endoplasmic reticulum, first to spherules, and later to a granular mass. Minute vacuoles appearing in the cytoplasm are parts of the distorted labyrinth and remains of the Golgi membranes. There is no disintegration of the outer cell membrane, and no hypertrophy of goblet cells. Nuclei remain in their posterior position and there are no cytoplasmic autophagic vacuoles in the centre. Cells in the same part of the midgut differ in the degree of disorganization. PMID- 8005003 TI - Multiple roles of intermediate filaments. AB - The widespread distribution, diversity of types, and highly conserved features of intermediate filaments (IFs) and the diversity of associated proteins indicate multiple roles for IFs in the nucleus and the cytoplasm of eukaryotic cells. Traditional functions include maintenance of cell shape, cell locomotion, movement and positioning of organelles and guiding cell development. Recent studies indicate some of these functions can now be expanded. Currently available information shows that IFs are important to nuclear function and cell division, to transport between the nucleus and cytoplasm, to the mechanical integrity of cells and tissues, to reorganization of the cytoplasm and chromatin in response to intercellular signals, and to embryonic and cellular differentiation. PMID- 8005004 TI - Viscosity effects on EMG activity in normal swallow. AB - This study investigated the effects of six consistencies on measures of swallow duration, muscle activity, and sound. Electromyographic (EMG) recordings of the submental and infrahyoid muscle complexes, and audio recordings of neck sounds were made while 5 normal subjects swallowed two foods in each of three consistency categories: liquid, thin paste, and thick paste. Total swallow duration, measured from EMG, increased significantly across consistency categories from liquids to thin pastes to thick pastes. Liquids and thin pastes were significantly different from thick pastes on all but one EMG measure. However, liquids and thin pastes failed to reach significance on any of the EMG measures. EMG activity in the submental muscles most often initiated the swallow whereas the infrahyoid muscle activity most frequently terminated the swallow. A sound spike occurred at relatively the same time in each swallow. Results are discussed in terms of systematic modulations of muscle activity during swallow. PMID- 8005005 TI - The use of scintigraphy in the management of patients with pulmonary aspiration. AB - Pulmonary aspiration was assessed using a scintigraphic swallowing procedure in 14 dysphagics in whom penetration of the larynx had been previously diagnosed. No patient had recent evidence of aspiration pneumonia. Imaging was performed during and following ingestion of a cupful of thin liquid admixed with between 1-2 mCi of Tc-99m sulfur colloid. Follow-up scans were obtained several hours later as needed to assess airway clearance. Five of the fourteen (36%) showed penetration distal to the trachea. Seven (50%) were indeterminate for aspiration, as isotope localized to the neck could not be clearly designated as being in either airway or foodway. Two subjects had negative studies. Of patients with subtracheal penetration, (1) fractions of the ingested material which were aspirated ranged from < 1%-25%, and (2) elimination from airways was complete or near-complete by 3 hours. The presence of an immediate or delayed cough was noted but did not correlate with subtracheal aspiration. Based on the results of scintigraphy, 8 of 9 patients on some form of liquid restriction at the time of testing were allowed to ease restrictions. Five patients without prior liquid restriction were allowed to continue to drink. We propose that scintigraphy provides important data on airway penetration and clearance that is useful in the dietary management of dysphagic patients. PMID- 8005006 TI - Objective distance measurements from videofluorographic swallow studies using computer interactive analysis: technical note. AB - Application of new technologies to study swallowing and its disorders will facilitate better understanding of both normal and disordered swallowing. Recent application of computer-assisted analysis of video-fluorographic swallow tapes has enhanced objective measurement of distance as well as timing characteristics of swallowing. Application of these systems requires consideration of system capability, calibration for distance measures, nature of measurements, and potential clinical/research benefits. This report describes a commercially available computer-interactive system for analyzing video images, discusses calibration procedures, and demonstrates practical applications using defined measures. PMID- 8005007 TI - Swallowing in neurological outpatients: use of a timed test. AB - Swallowing was studied prospectively in a consecutive group of 90 neurology outpatients under 70 years of age. No patient had been referred primarily because of dysphagia. Patients were classified into four groups: those with (1) neurological or (2) non-neurological diagnoses possibly relevant to disordered swallowing, (3) functional disorders, and (4) definite diagnoses not likely to be relevant. They were defined as having abnormal or probably abnormal swallowing if two or more of the following were present: a complaint of swallowing problem, abnormal symptoms or signs, a slow swallowing speed (< 10 ml.s-1). Nineteen patients among the four groups (21%) were found to have abnormal/probably abnormal swallowing. Swallowing speed was significantly slower in patients who perceived a swallowing problem or who had abnormal symptoms or signs compared with those who did not, providing further evidence for the validity of a timed test of swallowing capacity. The study also provides evidence of a significant incidence of disordered swallowing in outpatients who may not have complained spontaneously but who have diagnoses potentially relevant to swallowing. PMID- 8005008 TI - Comment on Cook: cricopharyngeal function and dysfunction. PMID- 8005009 TI - Esophageal cancer after mediastinal irradiation. AB - The authors report 4 patients, without a history of tobacco or alcohol abuse, who developed squamous cell carcinoma of the esophagus secondary to mediastinal irradiation. Carcinoma of the esophagus developed in 3 women 8-11 years after mediastinal radiotherapy for breast cancer and in a man 9 years after mediastinal radiotherapy for Hodgkin's disease. Three patients underwent resection, with intrathoracic anastomosis in 2 and cervical in 1. No fistulae were observed despite the presence of esophageal fibrosis. No mediastinal lymph node was metastatic. Patients survived 7, 16, and 26 months, respectively, after resection. This study confirms the concept of radiation-induced carcinogenesis. We conclude that patients with dysphagia and a history of previous mediastinal radiotherapy should undergo repeated endoscopy for biopsy. PMID- 8005010 TI - Malignancy-induced secondary achalasia. AB - Secondary achalasia refers to the development of clinical, radiographic, and manometric findings of achalasia as a result of (i.e., secondary to) another underlying disorder. A variety of malignancies have been associated with secondary achalasia. Adenocarcinoma of the esophagogastric junction accounts for the majority of cases of malignancy-induced achalasia, however, noncontiguous tumors may also cause this disorder. Although rare, malignancy-induced achalasia will occasionally be encountered by gastroenterologists and gastrointestinal radiologists who see patients with dysphagia and/or achalasia. Since treatment is aimed at the underlying neoplasm, it is important to recognize this disorder. Three clinical features suggest the possibility of malignancy as a cause of achalasia: 1) short duration of dysphagia (< 1 year); 2) significant weight loss (> 15 pounds); and 3) age > 55 years. The presence of any of these should at least raise a suspicion of malignancy. Diagnosis may not be evident on routine esophagrams and endoscopy, and requires clinical suspicion for further evaluation with thoraco-abdominal CT scanning and endoscopic ultrasonography. PMID- 8005012 TI - Temperature acceleration in cold oral stimulation. PMID- 8005011 TI - Temperature acceleration in cold oral stimulation. AB - This study measured the temperature acceleration of a cold probe as it contacts human tissue. Both the effects of touching a cold probe to the oral cavity were investigated. The results indicated a rapid warming pattern. This warming is effected first by temperature changes resulting from the probe being moved from ice into room temperature and second by the contact to oral mucosa. In fact, in some cases, the probe had reached minimal cold sensation levels by the time it reached the oral cavity. Results also indicated that 6 sec after the probe is lifted from the ice, the temperature closely approximates temperatures perceived as warm or at least neutral, but not cold. PMID- 8005013 TI - Videofluoroscopic predictors of aspiration in patients with oropharyngeal dysphagia. AB - The purpose of this investigation was to determine the relationship between aspiration and seven other variables indicative of pharyngeal stage dysphagia. Additionally, we looked at the relationship between aspiration and oral stage dysphagia. Multiple logistic regression analysis identified five independent predictors of aspiration that were significant at the p = 0.05 level: vallecular stasis, reduced hyoid elevation, deviant epiglottic function, diffuse hypopharyngeal stasis, and delayed initiation of the pharyngeal stage of the swallow. A linear trend was observed in that, as the severity of vallecular stasis, pyriform sinus stasis, diffuse hypopharyngeal stasis, or delayed initiation of the pharyngeal stage of the swallow increased, the proportion of patients who aspirated also increased. A stepwise logistic regression model furnished estimates of the odds ratio for each independent variable and can be used by clinicians to calculate the risk of aspiration in patients who demonstrate pharyngeal stage dysphagia. PMID- 8005014 TI - Dysphagia in postpolio patients: a videofluorographic follow-up study. AB - In patients with a history of acute paralytic poliomyelitis (APP), late progressive muscle weakness may arise, known as the progressive postpoliomyelitis muscular atrophy (PPMA). In 43 patients with PPMA, 8 were evaluated for recent or late progressive dysphagia. The mean interval between APP and onset of swallow symptoms was 27.1 years (range 23-45); the mean age of the patients was 45.4 years (range 35-52). Initial videofluorography showed signs of slight-to-moderate oropharyngeal dysfunction in 6 patients (delayed swallow reflex, diminished peristalsis of constrictor pharyngeus muscle, diminished laryngeal elevation, retention of bolus). In 2 patients, no abnormalities were found. Seven patients were reexamined after 12-36 months (mean 18). All reported subjective progression of symptoms. Videofluorography showed minor changes in 1 patient and unaltered findings in 6. No signs of aspiration were found either clinically or by video. We conclude that patients with PPMA complaining of late dysphagia do not show a significant loss in oropharyngeal function on 1-3 years follow-up. PMID- 8005015 TI - Postpolio dysphagia. PMID- 8005016 TI - When the problem is not the problem: understanding attention deficit disorder with and without hyperactivity. AB - Attention Deficit Disorder with, and Attention Deficit Disorder without, Hyperactivity, are common neurobiological conditions that cause or exacerbate many learning, social, and emotional problems. Understanding the significant interactions of biological, cognitive, and psychological factors in AD(H)D and informing clients of all treatment options, including pharmacological intervention, are essential to treatment. Counseling alone, without providing multimodal treatments that acknowledge the core medical problem, has limited positive effect. PMID- 8005017 TI - Assessing the safety of children at risk of maltreatment: decision-making models. AB - Child protective service caseworkers must make difficult decisions about the safety of maltreated children. Decision-making models for helping staff members balance the dual roles of child protection and family preservation are increasing. Results of a review of 10 models suggest that although some criteria overlap in these models, there are also wide differences in definitions, purposes, and the level of research support for the criteria being used to guide decision-making. PMID- 8005018 TI - Stages of emotion: an adult adoptee's postreunion perspective. AB - Increasing numbers of adoptees are searching for and finding their biological parents. This article is an attempt to alert counselors to the particular emotional state of adoptees postreunion. The theory presented is drawn from the author's personal experience and integrated with her perspective as a professional counselor. From these two vantage points, the author has concluded that there are four postreunion emotional stages: paralysis, eruption, loss and grief, and empowerment. Three factors have a direct bearing on the four stages: definition of reunion success, when reunion occurs, and the "female factor." PMID- 8005020 TI - Neural tube defects. Introduction. PMID- 8005019 TI - Clinical observations of adult intercountry adoptees and their adoptive parents. AB - This article presented data from interviews with 29 adult foreign-born adoptees and 23 adoptive parents, highlighting M.S.W. students' impressions of the interviewees' responses. The students' main observations stressed individualizing adoptees and their families, cautioning against falling into the all-too-easy trap of self-fulfilling labeled behavior. A second theme was the importance of each social worker's own sensitivity and attitudes toward this type of racial mixing, and emphasized professional and personal self-awareness. PMID- 8005021 TI - Genetic models of mammalian neural tube defects. AB - Several mouse mutations disturb the embryonic process of neurulation, yielding neural tube defects. Analysis of the mutations offers the most feasible approach to understanding the aetiology and pathogenesis of human neural tube defects. Interactions between the non-allelic mutant genes and between several of the mutant genes and modifying genes in the genetic background modulate the frequency and severity of the defects that develop. Environmental factors interact with the genetic predisposition either to increase or to decrease the incidence of defects. The gene loci corresponding to two of the mutations, splotch (Sp) and extra toes (Xt), have been identified as those encoding the transcription factors Pax-3 and Gli3, respectively; their human homologues are associated with Waardenburg type I syndrome and Greig's cephalopolysyndactyly. Embryological analysis reveals that several of the mutations disturb the process of neural tube closure at the posterior neuropore (in the lumbosacral region), yielding spina bifida and/or tail defects. The different mutations appear to achieve this developmental end-point by different underlying mechanisms. In curly tail (ct), non-neural tissues proliferate abnormally slowly causing ventral curvature of the neuropore region and inhibiting neural tube closure. Neural tube defects can be prevented in cultured ct/ct embryos by experimentally correcting either the proliferative imbalance or the ventral curvature. In Sp the primary defect appears to reside in the neuroepithelium. A combination of genetic analysis, gene cloning and experimental embryology is revealing that neural tube defects in mice and, by implication, in humans are a developmentally heterogeneous group of malformations. PMID- 8005022 TI - Valproic acid-induced neural tube defects. AB - Antiepileptic drug therapy with valproic acid (VPA) during early pregnancy can result in a 1-2% incidence of spina bifida aperta, a closure defect of the posterior neural tube in the human. The predominant defect produced by VPA in the mouse is exencephaly, a closure defect of the anterior neural tube. An appropriate dosing regimen (consecutive doses of VPA on Day 9 of gestation) can also result in a low incidence of spina bifida aperta and a high incidence of spina bifida occulta in the mouse. It is likely that the parent drug and not a metabolite is the proximate teratogen. Structure-activity relationships show a strict structural requirement for high teratogenic potency: the molecule must contain an alpha-hydrogen atom, a carboxyl function and branching on C-2 with two chains containing three carbon atoms each for maximum activity. If these two carbon chains are different, then enantiomers are present. Pairs of enantiomers were synthesized and shown to be significantly different in regard to teratogenic potency. Both enantiomers of each compound reach the embryo to the same degree, therefore, the intrinsic teratogenic activity of the enantiomers differs. This suggests that stereoselective interaction occurs between the drugs and a chiral structure within the embryo. The molecular mechanism of the teratogenicity of VPA is not known; one hypothesis is that VPA interacts with embryonic folate metabolism. PMID- 8005023 TI - Vitamins, folic acid and the cause and prevention of neural tube defects. AB - Primary prevention of neural tube defects has been demonstrated in humans by maternal therapy with multivitamins and folic acid or folic acid alone. It has also been shown in several animal models of neural tube defects. One of these, the curly tail mouse, has been used extensively to study which agents will prevent neural tube defects in embryos when administered to the mother in early pregnancy. Prevention is achieved with retinoic acid, inositol and the DNA inhibitors hydroxyurea, mitomycin C, 5-fluorouracil and cytosine arabinoside. In no case were neural tube defects prevented in every embryo. A possible preventive effect was seen with riboflavin, vitamin C and vitamin D2. Despite the use of a variety of dose levels, no prevention was achieved with folic acid, folinic acid, Pregnavite Forte F tablets, pyridoxine or vitamin B12, or triamcinolone and cycloheximide (inhibitors of mRNA and protein synthesis, respectively), zinc, homocysteine, methionine and thymidine. Various studies have investigated whether there is a biochemical lesion in folate metabolism in women who have had children with neural tube defects. While there is no difference in their dietary intake of folate compared with control patients, the correlation between their dietary folate and the level of folate in both serum and red blood cells is distorted. Also they are less efficient at raising their folate levels after a folate load. The effects are minor but may hint at a lesion which, if identified, could act as a marker for 'at risk' women. PMID- 8005024 TI - Folic acid metabolism and mechanisms of neural tube defects. AB - Folate acts as a cofactor for enzymes involved in DNA and RNA biosynthesis. Folate is also involved in the supply of methyl groups to the so-called methylation cycle, which uses methionine and makes homocysteine. The folate cofactor, N5-methyltetrahydrofolate, donates its methyl group to a vitamin B12 dependent enzyme, methionine synthase, which recycles homocysteine back to methionine. The cell's ability to methylate important compounds such as proteins, lipids and myelin will be compromised by deficiency of folate or vitamin B12, resulting in impaired cellular function. Methionine synthase plays another role: it converts circulating N5-methyltetrahydrofolate into tetrahydrofolate. The latter but not the former can act as a substrate for polyglutamate synthase, thereby becoming retained in the cell as polyglutamate. Interruption of DNA biosynthesis or methylation reactions could prevent the proper closure of the neural tube. Such inhibition could be caused by simple deficiency of either folic acid or vitamin B12. Studies comparing serum folate and vitamin B12 status in women who have had an affected pregnancy to those in control women indicate no difference between the two groups and show that most cases are not clinically deficient in either vitamin. A small number of studies using the level of folate in red blood cells, which is a better reflection of tissue stores, confirm this, suggesting instead a metabolic impairment in the biochemical functions of one of these vitamins. The trials using folic acid to prevent neural tube defects thus seem to be effectively overcoming a metabolic block rather than treating folate deficiency. PMID- 8005025 TI - Folic acid and neural tube defects: the current evidence and implications for prevention. AB - The results of the MRC Vitamin Study have established the specific role of folic acid in the prevention of neural tube defects. Folic acid supplementation (4 mg/day) at the time of conception reduced the recurrence rate by about 70%. Evidence from observational studies and the Hungarian randomized trial (that used 0.4-0.8 mg/day supplemental folic acid) indicates that a similar level of prevention can be achieved among women who have not already had an affected pregnancy and that this may be achieved with a lower dose of folic acid. The medical implications of these results are important. (1) Women planning a pregnancy should take folic acid supplements. (2) Because a large proportion of pregnancies are unplanned and many of those that are planned will occur in women who will not have taken folic acid supplements, a complementary general public health strategy is needed, based on dietary advice and food fortification designed to achieve the benefit with adequate safety. (3) Any public health prevention strategy needs to be monitored for efficacy and possible harm. (4) Research is needed on the dose-response relationship between folic acid and neural tube defect prevention and the mechanism of action. PMID- 8005026 TI - Prevention of folic acid-preventable spina bifida and anencephaly. AB - The results of the British Medical Research Council's randomized controlled trial proved that folic acid can prevent spina bifida and anencephaly. The trial provided critical scientific data upon which to base public health policy for preventing folic acid-preventable spina bifida and anencephaly. Within weeks of publication of the results, the Centers for Disease Control and Prevention in the US developed and issued guidelines for women who had had a pregnancy affected by spina bifida or anencephaly. A year later, the US Public Health Service issued the recommendation that all women of child-bearing age who are capable of becoming pregnant should consume 0.4 mg of folic acid per day. The Public Health Service needed a year to make inferential judgements about dose, target groups, safety, timing of ingestion, and existing and proposed vitamin and drug policies and regulations. Current policy discussions concern whether to permit manufacturers of vitamins or food products to claim that folic acid will prevent folic acid-preventable spina bifida and anencephaly and whether to allow a food staple to be fortified with folic acid. PMID- 8005028 TI - Formation and patterning of the avian neuraxis: one dozen hypotheses. AB - Formation of the neuraxis is dependent on cell-cell interactions and cell movements beginning during stages of gastrulation. Cell movements bring together new combinations of cells, allowing sequential inductive interactions to occur and leading to the specification of the neural plate and to its ultimate mediolateral (subsequently dorsoventral) and rostrocaudal patterning. Formation of the neural plate involves changes in the shape of its constituent cells and the first appearance of neural-specific cell markers. Shortly after the neural plate forms it undergoes 'shaping', in which the pseudostratified columnar epithelium constituting the neural plate thickens apicobasally, narrows transversely and extends longitudinally. Shaping is driven by three principal intrinsic types of cell behaviour: changes in cell shape, position and number. The next stage of neurulation begins while shaping is underway--bending of the neural plate. Bending involves two main processes, furrowing and folding. Furrowing of the neural plate is associated with the formation of the hinge points; these are localized, longitudinal areas where the neuroepithelium is attached to adjacent tissues and where wedging of neuroepithelial cells occurs. Cell wedging in the median hinge point occurs as a result of inductive interactions with the notochord; such wedging drives furrowing, thereby facilitating subsequent folding. Folding of the neural plate requires extrinsic forces generated largely by the surface ectoderm. Types of cell behaviour that could provide such forces include changes in cell shape, position and number. As a result of shaping and bending of the neural plate, the neural folds are brought into apposition in the dorsal midline. Final closure of the neural groove is mediated by cell surface glycoconjugates coating the apical surfaces of the neural folds. Patterning of the neuraxis begins during shaping of the neural plate and continues throughout stages of neurulation and into early postneurula stages. Patterning probably involves inductive interactions with adjacent tissues and the expression of putative positional identity genes such as homeobox containing genes. PMID- 8005027 TI - Spina bifida: anticonvulsants and other maternal influences. AB - At least two maternal conditions have been shown to be associated with an increased risk for the occurrence of anencephaly, spina bifida and encephalocele: insulin-dependent diabetes mellitus in the mother and maternal epilepsy for which anticonvulsant treatment is being used. Of 147 infants born at the Brigham and Women's Hospital with anencephaly, spina bifida and encephalocele among 123,489 live-born, still-born and elective terminations surveyed, 7.5% were infants of insulin-dependent diabetics and 0.7% had been exposed to anticonvulsants in utero. In addition to these proven causal associations neural tube defects have been postulated by some, but not all, studies as being more common among infants exposed to hyperthermia in utero and to drugs used to induce ovulation. PMID- 8005029 TI - Meningomyelocele: management in utero and post natum. AB - We report a four year follow-up of 39 of 47 infants born after pre-labour Caesarean section and 68 of 79 born vaginally. Loss of motor function due to late complications was more frequent in the Caesarean section group (Fisher's Exact; P = 0.004). However, the means of the differences between the X-ray levels (measured as the last intact vertebral arch seen on standard anteroposterior roentgenograms of the spinal column) subtracted from the motor levels still favour Caesarean section (mean = 3.24; SD = 2.7) over vaginal delivery (mean = 1.2; SD = 2.7) (Student's t-test; P = 0.0003). The frequencies of other complications, death and neonatal meningitis, were not significantly different. Another 38 infants born by Caesarean section after labour were more paralysed (mean of X-ray and motor difference = 1.8, SD = 2.2) following rupture of amniotic membranes than those with intact amniotic membranes with or without labour (mean = 3.4; SD = 2.2) (Student's t-test; P = 0.0067). The differences between X-ray and motor levels for patients born by Caesarean section with intact amniotic membranes and without labour (mean = 3.6; SD = 2.4) were not significantly different from those with labour and intact amniotic membranes (mean = 2.89; SD = 1.5). The number of new cases of meningomyelocele presenting to our clinic has decreased from an average of 30 per year between 1970 and 1987 to 14 between 1988 and 1992. PMID- 8005030 TI - Normal neurulation in mammals. AB - During mammalian neurulation regional differences are evident between the cranial region, in which neurulation is most complex, the trunk as far as the caudal neuropore and the secondary neurulation region of the caudal trunk plus tail. Differences among these three regions are characterized by specific patterns of morphogenesis and by specific patterns of gene expression. During cranial neurulation distinct regions develop in the brain and the presomitic hindbrain forms seven rhombomeric divisions. The first clear morphological boundary is the preotic sulcus (later transformed into the gyrus between rhombomeres 2 and 3), which may limit cell movement as neuroepithelial cells rostral to it flow towards and into the rapidly expanding forebrain region. The formation of rhombomeres as morphological entities and the development of a normal rhombomere-specific pattern of homeobox and other gene expression domains depend on relatively low levels of retinoic acid. Retinoic acid receptors, which are retinoic acid activated transcription factors, and retinoid binding proteins, which control the availability of retinoic acid to the receptors, show regional patterns of expression in the cranial, trunk and caudal regions of the neuroepithelium during neurulation. These patterns suggest a possible mechanism for region-specific gene expression during neurulation. PMID- 8005031 TI - Normal neurulation in amphibians. AB - How does cell behaviour accomplish neurulation in amphibian embryos? During neurulation, the neural plate (while preserving the same volume) doubles its length, triples its thickness, narrows 10-fold, greatly decreases its surface and rolls into a tube. Cells that compose the neural plate produce these changes in three ways. They change shape, change neighbours and attempt to crawl beneath the contiguous epidermis. Plate width, length and area are decreased and the plate thickens when apical surfaces of plate cells contract radially, but plate length increases and width is further decreased when cells reposition themselves and collect along plate boundaries. Contraction of the apical surfaces of plate cells also helps roll the plate into a tube. Poisson buckling resulting from elongation of plate borders may contribute bending forces that help tube formation. The main folding force in tube formation is a rolling moment toward the midline produced by neural plate cells attempting to crawl beneath the contiguous epidermis. Experiments, observations and computer simulations support these assertions, reveal the organization of cell behaviour and implicate contraction of actin filaments as the main source of the necessary forces. PMID- 8005032 TI - Neurulation in the normal human embryo. AB - The neural groove and folds are first seen during stage 8 (about 18 postovulatory days). Two days later (stage 9) the three main divisions of the brain, which are not cerebral vesicles, can be distinguished while the neural groove is still completely open. Two days later (stage 10) the neural folds begin to fuse near the junction between brain and spinal cord, when neural crest cells are arising mainly from the neural ectoderm. The rostral (or cephalic) neuropore closes within a few hours during stage 11 (about 24 days). The closure is bidirectional; it takes place from the dorsal and terminal lips and may occur in several areas simultaneously. The two lips, however, behave differently. The caudal neuropore takes a day to close during stage 12 (about 26 days) and the level of final closure is approximately at future somitic pair 31, which corresponds to the level of sacral vertebra 2. At stage 13 (4 weeks) the neural tube is normally completely closed. Secondary neurulation, which begins at stage 12, is the differentiation of the caudal part of the neural tube from the caudal eminence (or end-bud) without the intermediate phase of a neural plate. PMID- 8005034 TI - Cytopathology: in search of a new identity. PMID- 8005033 TI - Molecular genetics of neurulation. AB - The formation of the neural tube begins during gastrulation when ectoderm, an epithelial sheet on the outside of the embryo, is induced to form the neural plate. During the process of neural induction, the epithelium of the neural plate is regionalized along both the dorsoventral and anteroposterior axes of the embryo; this regionalization is likely to contribute to the cellular processes underlying neurulation. Genes whose expression marks the formation and regionalization of the neural plate and which encode cell adhesion molecules or putative transcription factors have been recently identified. The differential expression of these genes apparently subdivides the epithelium of the neural plate into small regions. Evidence from transgenic embryo experiments supports the idea that the differential expression of these genes in the neural plate plays a role in neural tube formation. PMID- 8005035 TI - Quality control study on negative gynecological cytology in Mexico. AB - An external evaluation of the quality of diagnosis of gynecological cytology specimens (Papanicolaou or "Pap" tests) in the Cytopathological Laboratory at the Mexico General Hospital was performed, with evaluation of 6,011 Pap tests randomly selected from 31,378 Pap studies previously reported as negative during 1988-1989. These tests were part of the early detection program for cervical cancer run by the Ministry of Health of Mexico City. A quality index for specimens was constructed based on the presence of endocervical cells, mucus, and squamous metaplastic cells. The index of false negatives for the diagnosis of cervical neoplasm in this sample which correspond to diagnostic error by the examiner was 0.18% (11). The constructed quality index revealed that 64.1% of specimens were low quality. The correlation between diagnostic error and low quality was .87. Results indicate that laboratories participating in early detection programs for cervical cancer in developing countries need to implement (1) external evaluation programs for Pap diagnosis; (2) permanent training programs in registration; and (3) monitoring procedures for collection, fixation, and transportation of cytologic materials. PMID- 8005036 TI - Papillary-cystic tumor of the pancreas in a young woman: fine-needle aspiration cytology, ultrastructure and DNA analysis. AB - A case of papillary-cystic tumor (PCT) of the pancreas in a young woman is reported. Fine-needle aspiration (FNA) was done preoperatively under ultrasound guidance. The aspirate showed numerous delicate papillary fragments, dyscohesive and monomorphic tumor cells with folded nuclear membranes, and foamy macrophages. A diagnosis of PCT of the pancreas was made based on clinical, radiologic, and cytologic findings. The patient underwent distal pancreatectomy without complications. The histopathologic examination of the surgical tissue confirmed the diagnosis of PCT of the pancreas. The tumor cells were faintly positive with mucicarmine and periodic acid-schiff (PAS) stains. Immunocytochemistry using Ki67 monoclonal antibody showed a cycling index of 0.1 percent, supporting the clinical observation of low metastatic and recurrence rates of this rare tumor. DNA analysis of the tumor showed a DNA index of 1.09 (diploid) and an S-phase fraction of 5.38%. The tumor cells were positive for progesterone receptors (> 15 fmol/mg protein) but negative for estrogen receptors (< 15 fmol/mg protein). Abundant mitochondria, prominent endoplasmic reticulum and few junctional complexes were noted on electron microscopy. Emphasis is placed on accurate diagnosis based on preoperative FNA cytology in order to maximize cure rates while minimizing surgical risk and complications. PMID- 8005038 TI - Cytologic features of papillary-cystic variant of acinic-cell adenocarcinoma: a case report. AB - A case of papillary-cystic variant of acinic-cell adenocarcinoma is described. The cytologic findings differed significantly from the classic features of this tumor with smears showing large monolayer sheets and small papillary groups, no acinic structures or naked tumor cell nuclei, sparse cell dissociation and many vacuolated cells. PMID- 8005037 TI - Low-grade squamous intraepithelial lesions: cytologic predictors of biopsy confirmation. AB - One hundred and seven smears demonstrating a low-grade squamous intraepithelial lesion (LSIL) were analyzed for features predicting subsequent biopsy confirmation. Twelve (29%) of 41 smears showing few LSIL cells were biopsy confirmed compared to 33 (60%) of 55 containing an intermediate number of LSIL cells and 9 (82%) of 11 displaying many LSIL cells (P < 0.002). Thirty-seven (47%) of 78 smears showing mainly condylomatous atypia (CA), 7 (54%) of 13 revealing predominantly cervical intraepithelial neoplasia 1 (CIN 1), and 10 (63%) of 16 displaying both CA and CIN 1 were histologically confirmed (N.S.). Biopsy confirmation was obtained in 35 (65%) of 54 women whose repeat smears obtained at colposcopy demonstrated SIL compared to four (15%) of 26 patients whose repeat smears were normal or contained atypical squamous cells of undetermined significance (P < 0.001). These results suggest that the number of diagnostic cells in an LSIL smear predicts biopsy confirmation and affirm the validity of combining CA and CIN 1 under the category of LSIL in the Bethesda System. PMID- 8005039 TI - Medulloblastoma metastatic to breast, diagnosed by fine-needle aspiration biopsy. AB - The extracranial spread of a primary intracranial tumor is an infrequent occurrence. The most common metastatic sites in order of frequency are bone, lymph nodes, and soft tissue. Analysis of the literature uncovered only two case reports of medulloblastoma that had metastasized to the breast. Both of these cases were diagnosed by open surgical biopsies. We present a case of medulloblastoma metastatic to the breast which was diagnosed by fine-needle aspiration biopsy. This diagnosis was subsequently confirmed by a tru-cut surgical biopsy and was further supported by immunohistochemical studies. PMID- 8005040 TI - Cytologic study of renal angiomyolipoma by fine-needle aspiration biopsy: report of four cases. AB - Four cases of renal angiomyolipoma (AML) diagnosed by fine-needle aspiration biopsy (FNAB) are reported. One case was associated with the clinical complex of tuberous sclerosis. The tumors were solitary in two cases and multiple and bilateral in the fourth. The cytologic features of the four cases were similar to those described in the literature: smooth muscle cells intermingled with mature fat cells and blood vessels, together with a lipoidic background. These tumors are currently considered benign although they may present characteristics accepted as criteria of malignancy in other tumors: pleomorphism and atypical smooth muscle cells, vascular invasion, capsular rupture, and lymphatic involvement. We conclude that it is important and possible to establish preoperative cytologic diagnosis, since treatment of these tumors is conservative and obviates aggressive nephrectomy. PMID- 8005041 TI - Fine-needle aspiration cytology of myositis ossificans: a case report. AB - This report describes the cytological findings of a case of myositis ossificans in a 16-yr-old girl. Clinically and radiologically she was suspected to have a malignant soft tissue tumor. This was not confirmed by fine-needle aspiration cytology and a diagnosis of benign lesion, probably myositis, was given. This diagnosis was confirmed by histological examination. PMID- 8005042 TI - Fine-needle aspiration cytology as a tool for the early detection of testicular relapse of acute lymphoblastic leukemia in children. AB - Fine-needle aspiration cytology (FNAC) of the testis was done in 31 children (33 aspirates) with acute lymphoblastic leukemia (ALL) either as part of an end therapy protocol (Group I, n = 20) or because of clinical suspicion of testicular relapse (Group II, n = 13). In Group I, none of the smears showed evidence of leukemic cells. However, two of these patients developed subsequent testicular relapse within 1 yr and were considered false-negative cases. Blast cells were present in nine patients of Group II; in the remaining four patients no neoplastic cells were observed in the smears and none experienced a relapse after a mean follow-up of 18 mo. Our findings indicate that FNAC can be a valuable method to evaluate clinically suspected testicular infiltration in children with ALL, and can be considered as an alternative procedure to surgical biopsy for screening testicular recurrence of childhood ALL. PMID- 8005043 TI - Metastatic myxopapillary ependymoma: report of a case with fine-needle aspiration findings. AB - A case of recurrent and metastasizing myxopapillary ependymoma of the sacral region in a 35-yr-old man is reported. Fifteen years after the original diagnosis, he presented with an abdominal mass, subcutaneous nodules in the previous surgical excision line, and bilateral inguinal lymph node enlargement. FNA cytology of the inguinal lymph nodes showed a poorly cohesive, highly cellular smear pattern exhibiting papillary formations and rosette-like structures composed of slim columnar cells having cytoplasmic processes without evidence of atypia. Histologic and ultrastructural findings confirmed the diagnosis. Chromosomal analysis was also done. PMID- 8005044 TI - Malignant rhabdoid tumor of the uterus: report of a case with findings in a cervical smear. AB - Rhabdoid tumors are an uncommon group of neoplasms which share a distinctive morphology. We report the cytologic and histologic findings of a uterine rhabdoid tumor. The presence of rhabdoid cells on a cervical Papanicolaou (Pap) smear raises an intriguing differential diagnosis. Cytologists should be aware of this entity and consider rhabdoid tumor in the differential diagnosis when single malignant cells are noted on cervical Pap smear. PMID- 8005045 TI - Fine-needle aspiration diagnosis of a vulvar papillary hidradenoma: a case report. AB - Papillary hidradenoma of the vulva, also know as hidradenoma papilliferum, is an uncommon lesion which occurs in post-pubertal women. Review of the literature yielded no fine-needle aspiration reports of the cytologic features of vulvar papillary hidradenoma. PMID- 8005046 TI - Comparative assessment of DNA analysis in effusions by image analysis and flow cytometry. AB - Cytologic evaluation of body cavity fluids is useful to detect malignancy within the pleural and peritoneal spaces. A definitive diagnosis cannot always be made on cytologic evaluation alone. As malignant processes may show abnormal DNA content, DNA analysis of effusions may be useful. Therefore, we determined the DNA content of 37 effusions by flow cytometry (FC) and image analysis (IA) using the CAS 200. Of the 37 fluids evaluated, 18 were cytologically malignant, 15 benign, and four atypical. Overall, 22 fluids (60%) showed concordance between FC and IA. None of the benign fluids were aneuploid. All showed diploid histograms or diploidy with increased proliferating cells. Three of four atypical fluids had increased proliferating cells by either FC or IA, whereas one was diploid by both methods. Aneuploidy was detected in 13 malignant fluids: five were aneuploid by both methods and eight by only one method. IA identified aneuploidy in five of those eight cases, while three were identified by FC. Three of the cytologically malignant fluids were diploid by both methods, and two showed increased proliferating cells by IA and diploidy by FC. The specificity of both methods was 100%. However, the sensitivity of identifying a malignant fluid by aneuploidy is low, 44% for FC and 55% for IA. IA appears to identify small aneuploid populations more frequently than FC. The detection of aneuploidy in effusions is highly suggestive of malignancy, and the combination of both techniques gives the highest detection rate (72%). However, neither are as sensitive as traditional cytologic evaluation with the occasional use of additional histochemical stains. PMID- 8005047 TI - Diagnostic accuracy in cytopathology. AB - Cytopathologic diagnoses play an important role in clinical decision making. As a result, the tests that produce material for cytopathologic interpretation must be evaluated critically and carefully. One way to evaluate these tests is by the assessment of diagnostic accuracy. The commonly used sensitivity and specificity format dichotomizes the data set and often loses or misinterprets important diagnostic information, especially the data which is semiquantitative. In addition, sensitivity and specificity do not allow the clinician to revise the probability of disease depending upon the test result. The LR and ROC analysis are two methods that systematically measure the diagnostic accuracy of tests, including those that produce semiquantitative data. LR and ROC measurements incorporate the concepts of sensitivity and specificity, but, in addition, provide a way to assess the clinical utility of a test by estimating the post test probability of disease. These methods are related to other techniques in medical decision making such as decision analysis and information theory, and are straightforward and easily utilized by clinicians and pathologists. PMID- 8005048 TI - Dithiothreitol homogenization of prefixed sputum for lung cancer detection. AB - The technique of chemical homogenization of sputum for cancer detection was revisited. The mucolytic agent dithiothreitol (DTT) had been used by the authors on fresh specimens. In this study, its effectiveness in homogenizing prefixed sputum was investigated. Fifty-seven positive samples were examined: 28 were prefixed with 2% carbowax in 60% ethanol and 29 in 3% carbowax in 60% ethanol. Each specimen was divided equally into three parts and homogenized immediately, 3 and 7 days later, respectively, with 0.2% (0.013 mol/L) DTT in the respective prefixative. Five samples were prefixed for 4 wk before homogenization. The homogenization time varied from 30 min to 48 hr. The cellular morphology was compared to directly smeared controls from the same samples. It was found that the cellular morphology was well preserved and best with the 3% carbowax in 60% ethanol. The specimen could be prefixed for up to 4 wk before homogenization and the homogenization process could last from 30 min to 48 hr without any damaging effect on morphology. Furthermore, screening was made easy with the mucus lysed and its obscuring effect removed and the cells concentrated and evenly distributed. The method was versatile and could be of value in enhancing the detection rate of cancer in sputum. PMID- 8005049 TI - Improved technique for fine-needle sampling of renal allografts. PMID- 8005050 TI - Response to editorial on the Pap smear as a cancer screening test. PMID- 8005051 TI - Acinic cell carcinoma arising in nasal cavity: diagnosis by fine-needle aspiration. PMID- 8005052 TI - Seasonal variation in genital tract infections as detected on Papanicolaou's smear examination. PMID- 8005053 TI - [Sex and age-dependent gaps in tetanus immunization]. AB - To test tetanus immunity, tetanus antitoxin titres were measured in the serum of 692 subjects (354 males, 338 females), aged one day (newborns) to 92 years (mean age 29 years). Those aged 18 to 65 years were first-time blood donors, the remainder were healthy newborns, while the children and those over 65 years were patients without immune-compromising disease. An inadequate protection (titre < 0.1 IU/ml) was found in 107 (15.5%), of whom 75 (70%) were females. Women aged 20 years and above also had significantly lower average antitoxin titres than men (1.7 vs. 3.5 IU/ml); P < 0.0001). The inadequate immunization protection of many young women is reflected in the lack of protective antibodies in 10 of the 49 examined newborns. In addition, 18% of children aged between 1 and 15 years had inadequate immunity against tetanus. In the whole group the titre level decreased with age, while the proportion of unprotected persons increased. Apart from the obvious age and sex dependency of the demonstrated inadequacy of immunological protection against tetanus, attention should also be paid to the lack of protective antibodies in newborns and the marked gaps of immunity among children. PMID- 8005054 TI - [Photometric determination of HbA1c levels in clinical practice]. AB - This study was undertaken to evaluate the routine use of a new immunological photometer to measure the concentration of HbA1c in whole blood from 155 patients. The basis of the measurement is a latex agglutination reaction in which a monoclonal antibody as epitope recognizes glucose bound to HbA1c. The result is available within 9 min. High-pressure liquid chromatography (HPLC) served as control method. The photometer proved to be very precise (all coefficients of variant < 2.5%), and the values obtained agreed well with those by HPLC (y = 0.952x-0.12; r = 0.986; P < 0.001). The reference ranges for the photometrically measured HbA1c values (4.4-5.9%), obtained for 40 patients, agreed well with those by HPLC (4.6-6.2%). Interference study discovered no effect on the measured value by anaemia, polycythaemia or high rheuma factor (n = 31). In 12 patients on dialysis the photometer recorded significantly lower values than HPLC (P < 0.0005). It is possible that in these cases the photometer values are more accurate because the method is not affected by carbamylated haemoglobin. False results were obtained by the photometer in two patients with leucocytosis (79,000 and 216,000/microliters, respectively) due to chronic lymphocytic leukaemia. PMID- 8005055 TI - [Successful resuscitation in severe hypothermia following near-drowning]. AB - A six-year-old boy fell into an ice-cold mountain stream and was immediately washed away. He was rescued 65 min later, 6 1/2 km downstream, seemingly lifeless with a rectal temperature of 16.4 degrees C. He was flown by helicopter to the surgical clinic of Innsbruck University, while resuscitation measures were undertaken by an accompanying doctor. After cannulation of the femoral artery and vein, extracorporeal circulation (ECC) with a child-size oxygenator was started and the blood rewarmed over 96 min in steps of 3 degrees C. Once circulatory stability and adequate cardiac output had been achieved ECC was gradually discontinued while the patient was still slightly hypothermic. Ten months after the accident the boy is restored to health, except for minimal residual neurological signs. There is a high chance for full neurological recovery. PMID- 8005056 TI - [Surgical therapy concept in Crohn disease]. PMID- 8005057 TI - [Significance of vitamin D and its metabolites in the pathogenesis and therapy of osteoporosis]. PMID- 8005058 TI - [No salary claims by medical co-workers upon medical administrator after dismissal by hospital underwriter. Decision of the Federal Labor Court, 7-21 1993]. PMID- 8005059 TI - [Penicillin therapy in streptococcal infections]. PMID- 8005060 TI - [Adjuvants in desensitization solutions]. PMID- 8005061 TI - [Stage-oriented therapy in non-seminomatous germ cell tumors]. PMID- 8005062 TI - [Clonidine therapy as cause of lupus erythematosus]. PMID- 8005063 TI - [Development of severely premature neonates]. PMID- 8005064 TI - [Combined conservative treatment of localized stomach lymphoma]. AB - In a twelve-year period (1980-1992) 23 patients (9 men, 14 women; mean age 65 [25 82] years) with malignant non-Hodgkin lymphoma of the stomach, in localized stage I or II (Ann Arbor classification), were given chemo- and radiotherapy without preceding operation. The results were compared with those of a group of 34 patients (19 men, 15 women; mean age 55 [17-77] years) who had been admitted during the same period, having first been treated by surgical resection and most of them additionally by chemo- and/or radiotherapy. Three not previously operated patients with inadequate response to chemotherapy subsequently underwent laparotomy and remained in remission after further treatment. There was in each group one fatal recurrence. Five-year total probability of survival in the operated and non-operated groups was 90% and 92%, respectively; five-year total recurrence-free probability was 88% and 86%, respectively. There were no cases of severe bleeding or perforation. These results demonstrate that conservative management of localized gastric lymphoma by combined chemo- and radiotherapy does not bring about a rise in recurrence rate and does not seem to be inferior to surgical treatment. PMID- 8005065 TI - [Successful treatment of a life-threatening ileostomy diarrhea with the somatostatin analog octreotide]. AB - A 72-year-old man with Crohn's disease for about 6 years was urgently hospitalized in hypovolaemic shock. On admission, serum creatinine concentration was 4.2 mg/dl, serum sodium 124 mmol/l, as a result of massive fluid and electrolyte loss via a loop ileostomy which had been placed 4 weeks previously because of a complicated perianal fistula. The basic aetiology of the diarrhoea probably lay in the previous resection of 30 cm of terminal ileum, other possible causes having been excluded. The ileostomy diarrhoea persisted despite the administration of loperamide, ranitidine, glucocorticoids, opium and pancreatic enzymes. Metronidazole, given in case the diarrhoea was due to a change in bacterial flora, also failed to achieve improvement. But when the somatostatin analogue octreotide was administered, the fluid loss via the ileostomy was quickly reduced so that both fluid and electrolyte infusions could be stopped. In subsequent months the initially required daily octreotide dosage of three times 100 micrograms could be reduced to once 50 micrograms subcutaneously. But it was not possible to stop this drug completely: it has now been continued and well tolerated for 2 years. PMID- 8005066 TI - [Imported cholera infection caused by a new nonagglutinating cholera agent]. AB - Within 24 hours of returning from a five-week holiday in Pakistan a 15-year-old girl developed vomiting and massive diarrhoea leading to severe dehydration with hypovolaemic shock. The diastolic blood pressure was no longer measurable and prerenal renal failure occurred with a serum creatinine of 4.4 mg/dl and metabolic acidosis (pH 7.21, base excess-16.9 mmol). Initially treatment consisted of rehydration (day 1: 9280 ml, day 2: 4850 ml). The patient's condition rapidly improved and she had voluminous stools. A concurrent urinary infection due to Klebsiella pneumoniae was first treated with cotrimoxazole. As a new strain of Vibrio cholerae, serogroup O 139, was isolated from stool, treatment was changed to tetracycline (50 mg/kg daily). Regaining a good general state she was transferred to an isolation ward on the 6th hospital day. The isolated cholera organism belongs to a nonagglutinating serogroup which is indistinguishable clinically and epidemiologically from the classical Vibrio strains which cause cholera. Since the end of 1992 this new serogroup has been causing an explosive spread of cholera in Bangladesh and India. PMID- 8005067 TI - [Diagnosis of focal liver lesions]. PMID- 8005068 TI - [Mechanisms of asbestos-induced diseases of the lungs and pleura]. PMID- 8005069 TI - [Risk of breast carcinoma and oral contraceptives]. PMID- 8005070 TI - [Menstrual cycle-related bleeding of a pilonidal sinus]. PMID- 8005071 TI - [Antral angiodysplasia ("watermelon stomach")]. PMID- 8005072 TI - [Glucocorticoid treatment of acute optic neuritis and multiple sclerosis risk]. PMID- 8005074 TI - Lip suture with isobutyl cyanoacrylate. AB - Reported are two cases of dental trauma with lip lesions and a deep wound through the muscular structures. The aim of this paper was to show that using an easy method with isobutyl cyanoacrylate that suturing small to deep lip wounds can be achieved without conventional sutures that require more time, and possibly may cause cheloid healing. PMID- 8005073 TI - A critical reevaluation of stresses generated during vertical and lateral condensation of gutta-percha in the root canal. AB - The finite element method was used to calculate the stresses in a maxillary canine tooth produced during lateral and vertical condensation. Description of the biological domain to be analyzed, and conversion of the manual operations of the endodontist to realistic load representation are intricate problems which must be overcome before stresses are recovered and plotted. The stresses in dentin are in general of comparable magnitudes during lateral or vertical condensation, but these magnitudes generally remain much below those presented in a previous study. From these calculations it appears that root fractures reported by some investigators may be explained in terms of stress concentrations and local irregularities of the samples tested. PMID- 8005075 TI - Unusual palatal root canal morphology in maxillary molars. AB - Three clinical cases are presented in which the palatal root(s) of human maxillary molars exhibited root canal morphology characterized by multiple canals/roots. PMID- 8005076 TI - Partially arrested root formation in a permanent maxillary central incisor subsequent to trauma to the primary dentition. AB - When the primary dentition sustains a traumatic insult, the development of the succedaneous teeth can be disturbed leading to a number of malformations. In this case report, the patient presented with a history of prior trauma to his primary maxillary incisors which resulted in partially arrested root formation for a permanent incisor. The considerations in formulating a treatment plan which included orthodontics are discussed. PMID- 8005077 TI - Dens invaginatus in first mandibular premolar. AB - A case of dens invaginatus in a mandibular first premolar with periapical lesion is presented in which it was possible to perform non-surgical endodontic therapy. Dens invaginatus is a developmental malformation of teeth which results from abnormal morphodifferentiation. Due to their abnormal anatomical configuration, invaginated teeth present technical difficulties in their clinical management. The treatment modalities available to the clinician include: endodontic therapy, endodontic surgery, combined treatment, or extraction. In this case the treatment of choice, selected according to clinical and radiographic considerations, was endodontic therapy of the main root canal. PMID- 8005078 TI - Introduction. Causes and mechanisms of linear growth retardation (stunting). AB - A workshop held 6 years ago examined the epidemiology and natural history of stunting in Third World children. Although this condition is extremely common and is usually regarded as a manifestation of chronic malnutrition, in fact almost nothing is known about its causes and mechanisms in nutritional, biochemical, or metabolic terms. The objective of the present workshop is to fill these gaps and to identify, if possible, critical mechanisms by which environmental factors might affect linear growth. An example is described of a longitudinal study which attempted to examine, in more detail than has been done before, what is happening to children during the process of becoming stunted. PMID- 8005079 TI - Effects of macrobiotic diets on linear growth in infants and children until 10 years of age. AB - In order to study the relationship between diet and growth, we have assessed growth patterns in children 0-10 years old on macrobiotic diets. A cross sectional anthropometric study (0-8 years old children, n = 243) indicated that deviation from the reference growth curve occurred during the weaning period. Between 2 and 4 years there was a partial catch-up for weight and arm circumference but not for height. As a next step, a mixed-longitudinal study was performed in 4-18-month-old macrobiotic infants (n = 53) and matched omnivorous controls (n = 57). For a period of 6 months, data on growth and dietary intake were collected. The data on linear growth supported the findings on growth stagnation observed cross-sectionally. Linear growth was associated with the protein content of the diet, but not with energy intake. On the basis of our findings nutritional modifications to the macrobiotic diet (addition of fat and fish) were recommended for all macrobiotic families. Six months later (two years after the first cross-sectional data collection) the anthropometric study was repeated in the same cohort (n = 194). This follow-up study revealed that children from families which, since the initial study, had increased the consumption of fatty fish, dairy products, or both, had grown in height more rapidly than the remaining children (P < 0.05). Since no indications were found for the presence of adverse social circumstances, infectious diseases or other confounding factors, our data clearly demonstrate that linear growth retardation in children on macrobiotic diets is caused by nutritional deficiencies alone. PMID- 8005080 TI - Psychosocial adversity and growth during infancy. PMID- 8005081 TI - Prenatal influences on postnatal growth: overview and pointers for needed research. PMID- 8005082 TI - Hormonal regulation of longitudinal bone growth. AB - The regulation of postnatal somatic growth is complex. Genetic, nutritional factors and hormones exert regulatory functions. Hormones that have an established role in the regulation include growth hormone (GH), thyroid hormone and sex steroids. GH promotes mainly the growth of the long bones in terms of final height, while the action of the sex steroids and thyroid hormone is less well known. Longitudinal bone growth is the result of chondrocyte proliferation and subsequent endochondral ossification in the epiphyseal growth-plates. The growth-plate is a cartilaginous template that is located between the epiphysis and the metaphysis of the long bones. GH and insulin-like growth factor-I (IGF-I) have different target cells in the epiphyseal growth-plate. GH stimulates the slowly dividing prechondrocytes in the germinative cell layer while IGF-I promotes the clonal expansion in the proliferative cell layer of a GH primed cell. Thyroid hormone blocks the clonal expansion and stimulates chondrocyte maturation. IGF-I mRNA is primarily regulated by GH, and IGF-I is produced in several tissues such as the liver, muscle, fat and epiphyseal growth plates. However, IGF-I mRNA is also increased during compensatory growth of heart and kidneys and by estrogen in the Fallopian tube in the rat. Nutrition, i.e. energy from fat and carbohydrates and proteins, also influences the final height, but the cellular mechanism of action is not known. The aim of this article is to review hormonal action on longitudinal bone growth. PMID- 8005083 TI - Adequacy of dietary mineral supply for human bone growth and mineralisation. AB - The evidence on the relationship between dietary mineral supply and bone development in children has been extensively reviewed. Data from children and primates suggest that overt deficiencies of Ca, P and Zn are likely to produce rickets and growth retardation, while the effects of Mg deficiency on human bone are unknown. The manifestations of marginal deficiencies are little understood. The biological needs for Ca, P, Mg and Zn in childhood have been calculated based on mineral deposition rates, using published values for the mineral content of the human body, and on obligatory endogenous losses. As a rough guide, the estimated biological requirements for the Ca, P, Mg and Zn can be taken as 200, 100, 4 and 1 mg/d respectively. A comparison of measured daily intakes of children in developing countries with biological requirements was made. This revealed that P and Mg intakes were many times higher than estimated needs. Ca intakes at all ages were found to be close to the biological requirement for children in many Third World societies, before any allowance for possible poor absorption. Zn intakes approach estimated needs in breast-fed infants, particularly during weaning, but are 4-5 times higher in older children. Poor absorption from phytate-rich diets could affect Zn supply. Supplementation studies indicate that raising Zn intakes can increase height gains in certain vulnerable groups, such as infant and adolescent boys. In conclusion, the evidence suggests that inadequate dietary intakes of Ca and Zn may contribute to linear growth retardation in children of developing countries but more research is needed. PMID- 8005084 TI - The mechanical factors which influence bone growth. PMID- 8005085 TI - Influence of exercise on linear growth. AB - The effects of exercise on linear growth were investigated in malnourished rats and in preschool children recovering from protein-energy malnutrition (PEM). Physical activity was either restricted or forced upon weanling rats that were pair-fed with 73 or 49% of the food eaten ad libitum by rats of the same age. Physically active animals grew more in length and weight than their inactive counterparts. In a subsequent study, 20 children, 24-48 months old, under treatment for severe PEM, were assigned to either an Active group (stimulated, but not forced, to participate in games and activities that involved walking uphill, climbing a ramp, running, tumbling and climbing stairs) or a Control group (with the ad libitum pattern of physical activity and rest commonly observed in child-care and nutrition rehabilitation centers). Dietary intake was controlled and almost identical in both groups (2.5 +/- 0.07 g protein and 117 +/ 7 kcal/kg/day). Mean energy expenditure during daytime, assessed by heart rate monitoring and its relationship with oxygen consumption, were 2.0 and 1.7 times basal metabolic rate in the Active and Control groups, respectively (P < 0.01). In 6 weeks, both groups gained an average of 1.98 kg. However, the Active group grew more in length (22 +/- 8 vs 14 +/- 6 mm, P < 0.05) and lean body mass (final creatinine-height index: 0.97 +/- 0.12 vs 0.89 +/- 0.09, P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8005087 TI - Biochemical markers for assessing skeletal growth. AB - Many of the biochemical markers for assessing skeletal turnover are based on the unique metabolism of fibrillar collagens. Intracellular modifications lead to the formation of hydroxyproline and hydroxylysine glycosides, both of which have been used as markers of collagen degradation. However, hydroxyproline is metabolised extensively in the liver and both components may be derived from several different tissue sources. The pyridinium crosslinks of collagen have been shown to provide more specific and sensitive markers of collagen degradation, since these compounds are only present in the mature, insoluble fibrils. In addition, pyridinium crosslinks are unaffected by diet and are not metabolised in the body. Following development of HPLC methods for the quantification of urinary crosslinks, these techniques have been validated as indices of bone resorption in studies of a wide range of metabolic bone diseases. Subsequently, the proportion of free crosslinks in urine was shown to be relatively consistent in different individuals, allowing development of a simple, direct immunoassay. The excretion of crosslinks in children was related to growth velocity and, in studies of malnourished children, the values before treatment were related to the child's growth response. For measuring bone formation, the serum concentrations of the C terminal propeptide of procollagen type I (PICP) appear to reflect the activity of the osteoblasts, but additional information on physiological variations is necessary. The major non-collagenous components of bone in serum, osteocalcin or bone Gla protein, has long been used as a marker of bone formation, but there are a number of factors that complicate interpretation of the results. These include variations in the immunochemical reactivity, the possible presence of degradation fragments in serum and the dependence of vitamin K status for adequate enzymatic carboxylation. Nevertheless, assays for intact osteocalcin have been shown to be related to growth velocity in children. There are few suitable serum or urinary indices for cartilage metabolism and development of more specific markers, particularly for growth plate cartilage, are required to distinguish between linear growth and bone remodelling. Assessments of skeletal metabolism should, wherever possible, include a combination of different markers so that the balance between formative and resorptive events can be adequately evaluated. PMID- 8005088 TI - Guidelines for the study of mechanisms involved in the prevention or reversal of linear growth retardation in developing countries. PMID- 8005086 TI - The effects of the inflammatory response on bone growth. AB - The inflammatory response is a process which forms a defence against the effects of trauma or invasion by foreign organisms or substances. Inflammation is mediated by local and systemic changes in expression of its activators and inhibitors. Many of these regulators of inflammation are also the controllers of normal cellular activity, so the effects of inflammation are due to changes in the amounts, ratios and timings of their expression, rather than de novo expression of specific mediators of inflammation. The effects of inflammation on bone growth are two-fold. Firstly, systemic inflammatory effects have consequences on hormone, mineral and nutrient metabolism which affect bone growth. Secondly, cytokine mediators of inflammation cause local changes in cell regulation to influence both endochondral processes in the growth plate, and modelling and remodelling activity associated with appositional growth. The complexity of the osteotropic influences responsible for maintaining normal bone development mean that inflammatory process will have different and unpredictable effects on linear growth at different times, and under different nutritional, biochemical, physical and psychological circumstances. This review will examine the effects of systemic and local changes in inflammation which have effects on bone growth and remodelling, focusing on systemic effects of the acute phase response, and the local actions of the eicosanoids and three cytokines with particularly potent actions on the metabolism of cells in bone and cartilage. PMID- 8005089 TI - Linear growth retardation in relation to the three phases of growth. PMID- 8005090 TI - Reversibility of stunting: epidemiological findings in children from developing countries. AB - The growth literature from developing countries is reviewed to assess the extent to which stunting, a phenomenon of early childhood, can be reversed in later childhood and adolescence. The potential for catch-up growth increases as maturation is delayed and the growth period is prolonged. However, maturational delays in developing countries are usually less than two years, only enough to compensate for a small fraction of the growth retardation of early childhood. Follow-up studies find that subjects who remain in the setting in which they became stunted experience little or no catch-up in growth later in life. Improvements in living conditions, as through food supplementation or through adoption, trigger catch-up growth but do so more effectively in the very young. One study cautions that in older adopted subjects, accelerated growth may accelerate maturation, shorten the growth period and lead to short adult stature. PMID- 8005091 TI - Between-population variation in pre-adolescent growth. AB - Between-population differences in rates of physical growth and development and attained body size are well documented, but it is difficult to determine the extent to which these differences can be attributed to genetic and environmental factors. The greatest differences are to be found between populations in industrialised and non-industrialised nations, and between well-off and poorer groups within countries. Although genetic factors cannot be discounted, such differences can largely be attributed to differences in environmental quality experienced, influencing growth largely through differentials in nutritional well being and exposure to, and treatment of, infectious disease. Growth patterns of well-off populations and groups of high socio-economic status are less heterogeneous, but differences between major global population groupings may still exist, bringing into question the validity of the concept of an international reference for the growth of young children. In this article, information pointing to genetic differences in the growth of children of different populations is summarised, and the acceptability of the NCHS (National Center for Health Statistics, 1977) references for height by age for international use is examined. It is concluded that the growth patterns of all major population groupings are likely to have similar genetic potential, with the exception of Asiatics. However, there are no data on either secular trends or well-off groups from populations that have until recently been genetically isolated, and it is not known whether they share the same potential for growth as the major populations that surround them. In addition, very little is known about the genetic potential for growth of Aboriginal populations in Australia, or in Pacific Islands populations. It is suggested that the growth references for height by age in current international use are at best only imperfect yardsticks for nutritional assessment. PMID- 8005093 TI - Relationship of gain in height to gain in weight. PMID- 8005092 TI - Is complete catch-up possible for stunted malnourished children? AB - Although malnourished children are stunted, their bone maturity is usually retarded to a comparable degree. This is seen in impoverished societies as well as in diseases such as coeliac disease, inflammatory bowel disease and hormonal deficiency. When these children are followed to adulthood they normally have some degree of spontaneous catch-up. With a change in environment, through adoption, emigration or with treatment of the disease there is usually definite catch-up growth, although it is often not to the NCHS standards. If puberty is delayed and/or growth continues into the early or mid twenties, then an acceptable final adult height is achieved. However, there may be a limitation imposed on an individual's maximum height by genetic imprinting in very early development. This may be the case where full catch-up appears to have taken place but is followed by an advanced puberty and early cessation of growth (Proos, Hofvander & Tuvemo, 1991a). The data from US slaves and cases of hormonal replacement, where treatment was initiated after age 18, each show that, if the circumstances of children in the Third World change, almost complete reversal of stunting is possible. The children can reach their own height potentials. Total reversal to affluent societal norms would probably require cross-generational catch-up. The most obvious reason why catch-up is not seen regularly is that an appropriate diet is not available over a sufficient period of time. We do not know the optimum ingredients for such a diet. Sulphur has been neglected as an essential nutrient; its economy should be examined in relation to skeletal growth in stunted populations. PMID- 8005094 TI - Nutritional influences on linear growth: a general review. AB - The first section of this paper reviews what is known about the roles of specific nutrients in the general linear growth faltering that occurs in developing countries. Those reviewed are energy, protein, zinc, iron, copper, iodine and vitamin A. For none of these nutrients was there clear, consistent evidence that supplementation with the nutrient benefited linear growth. Rather, interventions with each specific nutrient had a positive effect on length gain in some studies, while in others these affected only weight gain or had no effect. Reasons for these conflicting results are suggested, including the strong probability that growth is limited by multiple, simultaneous deficiencies in many populations. This point is illustrated with data from the Nutrition Collaborative Research Support Program (CRSP) and other reports. Most interventions with single nutrients have been tested on children older than the age when linear growth faltering is most rapid, that is, within a few months of birth. Possible reasons why growth stunting begins so early in life are presented, but these are mostly hypothetical because of the paucity of information on this topic. PMID- 8005095 TI - Onset and evolution of stunting in infants and children. Examples from the Human Nutrition Collaborative Research Support Program. Kenya and Egypt studies. AB - The etiology of the early onset of stunting is diverse among populations of varying biological, environmental and cultural circumstances. This is exemplified within the Nutrition CRSP project, which took place in three different populations and ecological conditions. Within each study area a different mix and varying proportions of causative factors were identified. At least in Kenya, and probably in Mexico, the problem has its antecedents in prepregnancy and pregnancy. Powerful determinants of the infants' size at birth and during the first 6 months of life are maternal size upon entry into pregnancy, and weight and fat gain during pregnancy and lactation. In all three countries a low pregnancy weight gain was observed. Notably in Kenya, where the energy intake of the mother decreases progressively throughout pregnancy, not only do mothers gain only half as much as European or North American women, but they even lose weight and fat in the last month of pregnancy, and some mothers gain no weight or lose weight during the whole of pregnancy. Mothers in Kenya start lactation with relatively poor fat stores. Although their energy intake increases somewhat during lactation, preliminary estimates suggest that these increases may be insufficient to maintain their bodily integrity, to carry out their normal tasks of daily living, and to produce a sufficient amount of milk for optimal infant growth. In addition to an energy deficit, diet quality is a problem, particularly in Kenya and Mexico and less so in Egypt. Intakes of animal products and animal protein are very low. Zinc and iron intakes are not only low, but the bioavailability of these nutrients is poor because of the high phytate, fiber and tea content of the diet. Also vitamin B12 intake is extremely low, and at least mild-to-moderate iodine deficiency (IDD) is present in Kenya. The above micronutrients have been demonstrated to affect the linear growth of the Kenyan children, even after confounding factors have been controlled. The early use of supplemental feeding in Kenya is a double-edged sword. On the one hand, there is a slight increase in febrile illness and possible displacement of breast milk intake in the supplemented infants, although mothers do not decrease breast feeding frequency and duration. On the other hand, even the modest amounts of available zinc and B12 in supplemental foods appear to have a positive effect on linear growth.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8005096 TI - Intracellular sites involved in the biogenesis of bile canaliculi in hepatic cells. AB - Studies in hepatoma cells and hepatocytes have revealed that the biogenesis of bile canalicular membrane involves microvilli-lined vesicles (MLV), which are formed in well differentiated cells. The vesicles grow as a function of time and are presumably vectorially transported to cell surface contact sites of attached cells. We demonstrate that a fluorescent head group-labeled lipid analog, N (lissamine rhodamine B sulfonyl)phosphatidylethanolamine (N-Rh-PE), after its exogenous insertion into the plasma membrane of HepG2 cells at 4 degrees C, accumulates in these microvilli-lined vesicles at 37 degrees C. This shows that the MLV are a target for plasma membrane-derived lipids. Furthermore, also the Golgi apparatus is involved in the formation of the vesicles. After initial accumulation of the fluorescent sphingolipid precursor, 6-[N-(7-nitrobenz-2-oxa 1,3-diazol-4-yl)amino]hexanoic acid (C6-NBD)-ceramide in the Golgi apparatus at 37 degrees C, prolonged incubation at 37 degrees C results in the appearance of NBD fluorescence in the microvilli-lined vesicles. The transport route for the Golgi-derived material to the developing bile canalicular vesicle is not an indirect pathway, i.e. involving transcytosis via the basolateral plasma membrane. This could be demonstrated by including bovine serum albumin (BSA) in the incubation media, a lipid scavenger that will remove any C6-NBD-lipids exposed at the basolateral membrane. At these conditions, lipid trafficking between the Golgi complex and MLV still occurred. We further demonstrate that the targeting from the Golgi apparatus to the bile canaliculus is also operational in isolated human hepatocytes. The latter results suggests that the Golgi complex is involved in both the formation of bile canaliculi and in bile secretion in fully differentiated cells. PMID- 8005097 TI - Expression of N-CAM in fertilized pre- and periimplantation and parthenogenetically activated mouse embryos. AB - The expression of the cell adhesion molecule of the immunoglobulin family, neural cell adhesion molecule (N-CAM), in the pre- and periimplantation embryo was examined by immunocytochemistry. N-CAM is expressed on unfertilized ovulated oocytes, fertilized preimplantation embryos at all stages of development and parthenogenetically activated eggs and embryos. In fertilized embryos, expression from the 4-cell stage can be partially inhibited by blocking embryonic transcription before 38 h post human chorionic gonadotropin (hCG). Expression of N-CAM was reduced on the trophoblast of day 6 blastocysts in culture, weak on the trophoblast of embryonic outgrowths and disappears from invading trophoblast in utero. An antibody against alpha(2-8) linked polysialic acid, mAb2-2B, reacted with embryos from the 8-cell stage, and staining was similarly reduced on the trophoblast of blastocysts at the time of implantation. These results suggest a role for N-CAM in the interactions of cells of the preimplantation mammalian embryo which requires further investigation. PMID- 8005098 TI - Inhibition of chondrogenesis and endochondral mineralization in vitro by different calcium channel blockers. AB - Limb bud mesenchymal cells from mouse embryos grown at high density at the medium/air interphase undergo chondrogenesis and form numerous nodules of mature cartilage. Addition of beta-glycerophosphate (5 mM) induced endochondral mineralization within these nodules. Ca2+ accumulation, matrix formation and alkaline phosphatase activity were recorded for each culture. Treatment with the L-type channel-specific blockers nifedipine and verapamil during the entire culture period caused an inhibition of mineralization. Sequential treatment reduced mineralization only when added during the early part of the culture period in the course of chondrogenesis. In all cases, matrix formation, estimated by alcian blue binding, was concomitantly diminished. Lanthanum acetate, which blocks Ca2+ channels non-specifically, also reduced Ca2+ accumulation in the cultures when added continuously. After sequential treatment, Ca2+ content was only diminished when the cultures were treated in the last part of the culture period during mineralization. Matrix formation was not altered by lanthanum acetate, but alkaline phosphatase was decreased. These results show that chondrogenic differentiation is under control of L-type Ca2+ channels, whereas matrix calcification depends on intracellular Ca2+ accumulation mediated by lanthanum-sensitive Ca2+ channels. This points to the importance of intracellular Ca2+ accumulation in the process of endochondral mineralization. PMID- 8005100 TI - Activity of Kex2 dibasic endoprotease is localized throughout the secretory pathway in Saccharomyces cerevisiae. An ultracytochemical study. AB - The sites of calcium-dependent dibasic endoprotease (Kex2; yscF) activity have been ultracytochemically localized in exponential cultures of haploid (alpha) wild-type strain of Saccharomyces cerevisiae, in its pep4-3 mutant and in the kex2 mutant. The gently prefixed cells were thoroughly washed and incubated in a buffered mixture containing Ca2+, benzyloxycarbonyl-L-tyrosyl-L-lysyl-arginin-4 methoxy-2-naphthylam ide (Z-Tyr-Lys-Arg-MNA) as substrate and hexazotized p rosaniline (HPR) as coupler of the liberated MNA. The precipitated azo-dye was osmicated, and the cells were embedded for ultrathin sectioning. In the pep4-3 mutant the reaction product labeled the periphery of lipoprotein condensates, the lumen of nuclear envelope plus endoplasmic membrane cisternae, the matrix of juvenile vacuoles and the lumen of microvesicles--the membrane vesicles and the smaller coated or uncoated globules. These were dispersed in the cytoplasm or in the senescent vacuoles. The reaction product labeled also both faces of the plasmalemma-restricted cells. In the presence of EDTA the reaction product appeared only in the lipoprotein condensates. In the absence of substrate and in the presence of HgCl2, no reaction product was formed. In the wild-type strain the enzyme activity was detectable in the cytoplasmic microvesicles and in the tonoplast of vacuoles. No reaction product formed in the kex2 mutant cells. Enzymic assay of total activity of dibasic endoprotease in investigated strains confirmed the substrate was hydrolyzed principally by calcium-dependent protease. The study was supplemented by ultracytochemical localization of glycoproteins in cells of secretory mutants cultivated under restrictive conditions. The results of both topochemical studies give further arguments against the established model of a polar compartmentalized Golgi apparatus in S. cerevisiae. PMID- 8005099 TI - The fungal hydrophobin Sc3p self-assembles at the surface of aerial hyphae as a protein membrane constituting the hydrophobic rodlet layer. AB - The Schizophyllum commune hydrophobin Sc3p is a small, hydrophobic, cysteine-rich protein involved in the formation of aerial hyphae. Using an antibody against purified Sc3p we found that the hydrophobin is secreted into the medium at the apices of growing submerged hyphae but in emerging aerial hyphae it accumulates at the hyphal surface. Here, the hydrophobin self-assembles at the wall/air interface into an SDS-insoluble protein membrane, at the aerial site very hydrophobic and with the appearance of a mosaic of 10 nm spaced parallel rodlets. Interfacial self-assembly of the hydrophobin also occurs in vitro. When solutions containing various concentrations of purified Sc3p were dried down onto a glass surface, the amount of assembled Sc3p depended on the area of the interface. Surplus of Sc3p remained in the monomeric form, apparently because formation of a monolayer of assembled Sc3p abolishes the hydrophilic/hydrophobic interface. The 10 nm thick layer of assembled Sc3p at the surface of aerial hyphae thus probably represents a monolayer of the protein. PMID- 8005101 TI - Okadaic acid promotes cell division in synchronized Tetrahymena pyriformis and in the cell division-arrested (cdaA1) temperature-sensitive mutant of T. thermophila. AB - 1. Okadaic acid (OA) at 0.5 to 1 microM accelerated the onset and completion of division in heat-synchronized Tetrahymena pyriformis, especially where cells had been transiently delayed in the presence of dimethyl sulfoxide (DMSO). 2. The cell division-arrested mutant, cdaA1, of Tetrahymena thermophila ceased dividing after being shifted from the permissive temperature of 22 degrees C to the restrictive temperature of 37 degrees C, but continued to grow without forming fission furrows, resulting in deformed "monsters". In the presence of 1 microM OA, monster formation was completely inhibited, and over 20% of the mutant cells at 37 degrees C proceeded through a further apparently normal division. Evidence is presented for the first time that the potent and relatively selective PP2A inhibitor, okadaic acid (OA) can promote the entry and completion of Tetrahymena cell division as opposed to simply aiding the premature appearance of M-phase events seen in other cell systems. In this regard, the differential response to the combined action of OA and the kinase inhibitor 6-dimethyl-aminopurine (6 DMAP) at chosen stages of the cell cycle is shown. At early division, inhibitory effects of 6-DMAP were enhanced by the presence of OA, whereas in advanced stages of division, OA treatment by-passed 6-DMAP-induced inhibition and accelerated cells through division. The results are discussed in terms of the actions of these drugs on phosphorylation/dephosphorylation events responsible for driving division. PMID- 8005102 TI - Adenine nucleotides regulate ADP-ribosylation of membrane-bound actin and actin binding to membranes. AB - Adenine nucleotides were shown to increase the ADP-ribosylation of actin by Clostridium perfringens iota and Clostridium botulinum C2 toxin in membranes from human platelets, hamster fat cells, rat liver- and rat brain cells. ATP and ATP gamma S were the most effective agents with ATP showing half-maximal and maximal effects at about 2 and 10 microM, respectively. The rank order of various adenine nucleotides were ATP = ATP gamma S > ADP > AMP-PNP >> AMP = cAMP. Guanine nucleotides showed the same rank order of potencies but were less effective than adenine nucleotides. Adenine nucleotides which increased ADP-ribosylation were able to release actin from membranes. [32P]ADP-ribosylated rabbit skeletal muscle actin, which is unable to polymerize, was used as tool to study membrane-binding of actin. The [32P]ADP-ribosylated actin bound to stripped rat liver membranes in a saturable, time- and temperature-dependent manner. ATP inhibited the binding of ADP-ribosylated actin with a half-maximal and maximal inhibitory concentration at about 50 and 300 microM, respectively. The data indicate that actin-binding to membranes is prevented or reversed in the presence of adenine nucleotides thereby increasing the accessibility of actin for ADP-ribosylation by toxins. PMID- 8005103 TI - Morphology and element distribution of magnesium-secreting epithelium: the proximal tubule segment PII of dogfish, Scyliorhinus caniculus (L.). AB - Proximal tubule segment PII cells of marine elasmobranch fish were studied by transmission electron microscopy of thin sections, and X-ray microanalysis was performed with freeze-dried cryosections. Epithelial cells of PII are characterized by high and dense brush border at the apical side, elaborate folding of the lateral cell membrane and large basal extracellular labyrinth confined by a system of meandering cell extensions. Basal cytoplasmic zone, apical cytoplasmic zone, nuclei, mitochondria and apical small vacuoles were accessible for X-ray microanalysis. Concentrations of Na, Mg, P, S, Cl and K were different in the cytoplasmic zones along the basal-apical axis of the cell and in the organelles. PII cells lacked an apical tubulovesicular apparatus, instead they displayed an apical zone of smooth clear vesicles and small apical vacuoles. After freeze-drying, the small apical vacuoles and the smooth clear vesicles contained flocculent mass-dense material. Small apical vacuoles showed high concentrations of Mg (229 mmol/kg water), Na (132 mmol/kg water) and Cl (148 mmol/kg water). Sequestration of Mg in vesicles and small apical vacuoles and subsequent exocytosis between the microvilli of the brush border are supposed to be important steps in the transepithelial transport (tubular secretion) of magnesium by PII cells of marine fish. PMID- 8005104 TI - Expression of syndecan-1 is induced by differentiation and suppressed by malignant transformation of human keratinocytes. AB - Syndecans comprise a family of integral membrane proteoglycans that presumably participate in cell-matrix interactions and the modulation of growth factor response. Expression of syndecan-1, a cell surface proteoglycan that binds basic fibroblast growth factor (bFGF) and extracellular matrix components, was studied in cultured human keratinocytes from the oral mucosa and in tissue sections derived from various epithelia and carcinomas of the head and neck. For the study, polyclonal antibodies were raised against the core protein of human syndecan-1. The affinity-purified antibody (designated anti-P117) was shown to react specifically with syndecan-1. Abundant expression of syndecan-1 was detected in frozen sections of various stratified epithelia as well as in cultured keratinocytes. Keratinocytes located in the spinous cell layers showed intense immunoreactivity for syndecan-1, while basal cells stained rather weakly, suggesting that the expression of syndecan-1 could be stimulated during the differentiation of keratinocytes. Cultured human keratinocytes were induced to terminally differentiate by increasing the extracellular calcium concentration of the medium. Parallel to the induction of involucrin expression, the mRNA levels of syndecan-1 were found to increase, suggesting that syndecan-1 is indeed induced during keratinocyte differentiation. The molecular mass and glycosaminoglycan composition of syndecan-1 did not change markedly during calcium-induced differentiation. Malignant transformation was associated with marked reduction of syndecan-1 expression, based on the immunoreactivity of anti P117 in frozen sections from squamous cell carcinomas (SCCs) of the head and neck.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8005105 TI - Glycogen stores in mature ovarian follicles and young embryos of Drosophila: ultrastructural changes and some biochemical correlates. AB - During the last phase of oogenesis in Drosophila, large amounts of carbohydrates are taken up by the oocyte and become stored in the so-called beta-spheres whose ultrastructure and histochemical properties indicate that glycogen is the predominant storage form. The ultrastructure of the beta-spheres changes at the onset of embryogenesis: they become irregular in shape and the spacing of the granular substructures (beta-particles) increases. During the first 2 h of embryonic development, the total carbohydrate content decreases sharply while at the same time the protein content increases. Presumably the carbohydrate store is used to generate energy at this phase of development. Using monoclonal antibodies against an ecdysteroid-related antigen we showed that this antigen is mostly located in the beta-spheres. The asymmetrical distribution of the antigen in the egg (more concentrated near the posterior end) correlates with the same asymmetrical distribution of the beta-spheres in the mature follicle. PMID- 8005106 TI - Light-induced changes in S-antigen (arrestin) localization in retinal photoreceptors: differences between rods and cones and defective process in RCS rat retinal dystrophy. AB - The subcellular localization of S-antigen (arrestin), a protein regulating phototransduction in retinal rods, was studied by immunocytochemistry using monoclonal antibodies on sections of Swiss mouse, Lewis, Brown Norway (BN), Royal College of Surgeons (RCS) rdy-p+ (dystrophic) and RCS rdy(+)-p (non-dystrophic) rat retinas. In normal retinas, the topography of S-antigen immunoreactivity in photoreceptor cells varied according to the lighting environment of the animals. In dark-adapted eyes, outer segments did not display any S-antigen immunoreactivity while the inner segments, cell bodies and synaptic terminals were strongly labeled. A few minutes after light exposure, there was an inversion of the pattern of labeling: the label increased in the outer segment but was strongly reduced in the other compartments. After 1 h of light, S-antigen immunoreactivity remained only in outer segments and in a few synaptic terminals. We show that the kinetics of this change is slower in cone than in rod cells, and thus allows the transient visualization of the scarce cone photoreceptors. On the 17th day after birth, photoreceptor cells are well differentiated in all rat strains, including RCS rdy-p+ rats. At this time, the S-antigen shift phenomenon occurred in the non-dystrophic strains, but was not observed in rdy-p+ rats: after light exposure, the intracellular distribution of S-antigen remained the same as in the dark. We suggest that an abnormality in the mechanisms of intracellular protein transport could be a characteristic of this genetic disease. PMID- 8005107 TI - Intracellular free calcium concentrations in cell suspensions during hyperthermia. AB - The aim of this study was to explore the possibility that heat-induced alterations in calcium homeostasis are the cause of hyperthermic cell killing. Therefore, the intracellular free calcium concentration ([Ca2+]i) was determined spectrofluorometrically, using the fluorescent calcium probe fura-2/acetoxy methylester (AM), at both physiological and hyperthermic temperatures in cell suspensions from six different tumor cell lines. For all cell lines fura-2 leakage appears to contribute to a change in the fluorescence signal and hence leads to a false indication of an increase in [Ca2+]i, especially at the hyperthermic temperature. Two methods were introduced that circumvent this problem and results in true values of [Ca2+]i. Also, measurements of [Ca2+]i in single cells using a fluorescent microscopical technique (not affected by dye leakage) were used for comparison. All three approaches show that a hyperthermic treatment that kills > 90% of the cells does not lead to changes in the [Ca2+]i in most cell lines. Therefore, heat-induced alterations of calcium homeostasis cannot be considered the general cause for hyperthermic cell killing. PMID- 8005108 TI - Intracellular distribution of kinesin in chromaffin cells. AB - In this paper we examined the association of the microtubule motor protein kinesin with organelles in chromaffin cells. Approximately 15% of kinesin was associated with membranes as determined by differential and equilibrium centrifugation on sucrose gradients. Kinesin was not enriched in a particular organelle fraction but cofractionated with a variety of organelle markers including markers for early and late endosomes, smooth and rough endoplasmic reticulum (ER) and the Golgi apparatus. Surprisingly, low amounts of kinesin were present in fractions of purified chromaffin granules. The absence of kinesin from the bulk of chromaffin granules was also indicated by immunostaining of tissue sections. A polyclonal antibody that specifically recognized the 120 kDa kinesin heavy chain labeled predominantly a perinuclear region that is typical for most of the kinesin-binding organelles identified by cell fractionation (endosomes, Golgi, ER). Since these organelles are compartments with high membrane turnover, we speculate that kinesin might be involved in certain aspects of trafficking of these membrane systems. PMID- 8005109 TI - Developing renal microvasculature can be maintained under perfusion culture conditions. AB - The cortex corticis of the neonatal rabbit kidney consists of developing nephrons, vessels, collecting duct ampullae and the nephrogenic mesenchyme. Inductive interactions between embryonic mesenchyme and collecting duct ampullae lead to the coordinated development of the nephrons and the collecting duct system. The factors regulating nephrogenesis and vascular development within this tissue region are unknown. In order to analyze the hormonal regulation of vascular development an organotypic culture system was established. Cortex explants from neonatal rabbit kidneys were prepared, mounted in a set of holding rings and cultured under serum-free conditions for 14 days in conventional culture plates or under permanent medium perfusion in a newly developed culture container. The detection of endothelial cells was carried out by means of two monoclonal antibodies. Within the renal cortex corticis EnPo 1 detected developing vasculature as well as podocytes and a subset of mesenchymal cells. EC1 displayed exclusive specificity for endothelial cells. The antibody did not discriminate between arteries and veins. Endothelial cells of different developmental stages were labeled with the same intensity. A combination of both antibodies allowed the discrimination between developing endothelial cells and podocytes. Following 14 days of culture under permanent medium exchange, excellent tissue preservation as well as endothelial cell proliferation was observed in cortex explants. In contrast, tissue kept in stationary culture revealed a high degree of disintegration. Endothelial antigen expression was also severely disturbed. Tissue maintenance under stationary conditions was improved by the application of a hormone mixture consisting of aldosterone and 1,25 hydroxyvitamin D3. However, the high degree of spatial organization shown by developing endothelial cells in vivo was maintained exclusively in explants cultured in the presence of hormone under permanent perfusion. PMID- 8005110 TI - The human breast cancer cell line MDA-MB231 produces an aromatase stimulating activity. AB - Extraovarian estrogen production is localized mainly in stromal vascular cells from adipose tissue, which contain the aromatase activity necessary for the conversion of androgens to estrogens. Induction of aromatase activity in these cells by glucocorticoids occurs only in the presence of a serum factor, the properties and origin of which are unknown (serum-derived aromatase stimulating activity, serum-ASA). Cells of the breast cancer line MDA-MB231 produce a factor resembling serum-ASA, as it is able to completely replace serum during the induction of aromatase by glucocorticoids. MDA-MB231-derived ASA is destroyed by proteolytic digestion and is purified about 100-fold by ultrafiltration of MDA MB231 conditioned media and anion exchange chromatography. PMID- 8005111 TI - Principles of platelet inhibitor therapy--where we stood in 1993. PMID- 8005112 TI - Clinical epidemiology and experimental biology in cardiology: the two faces of the same coin. PMID- 8005113 TI - Paediatric cardiology and cardiac surgery in Europe. PMID- 8005114 TI - Paediatric cardiology in Europe--medical/scientific statement of the Association of European Paediatric Cardiologists. Definition of profession and training requirements. AB - The treatment of growing and developing individuals with heart and circulation diseases demands expertise and organization. Due to the unification of Europe, international exchange of doctors can take place. The Association of European Paediatric Cardiologists had laid down professional and training requirements to harmonize the field of patient care, training and training institutes all over Europe. PMID- 8005115 TI - Influence of the force-frequency relationship on haemodynamics and left ventricular function in patients with non-failing hearts and in patients with dilated cardiomyopathy. AB - In isolated human myocardium it was shown that a positive force-frequency relationship occurs in non-failing myocardium; however, the force-frequency relationship was found to be inverse in myocardium from failing human hearts. In order to investigate the clinical relevance of these experimental findings, the influence of heart rate changes on haemodynamics and left ventricular function was studied in eight patients without heart failure and in nine with failing dilated cardiomyopathy (NYHA II-III). Right ventricular pacing was performed at a rate slightly above sinus rate and at 100, 120 and 140 beats.min-1. Haemodynamic parameters were obtained by right heart catheterization and by high-fidelity left ventricular pressure measurements. Left ventricular angiography was performed at basal pacing rate and at 100 and 140 beats.min-1. With increasing heart rate, cardiac index increased in patients with normal left ventricular function from 2.9 +/- 0.2 to 3.5 +/- 0.21.min-1.m-2 (P < 0.01) and decreased continuously in patients with dilated cardiomyopathy from 2.6 +/- 0.1 to 2.2 +/- 0.1 l.min-1. m-2 (P < 0.05). With increasing heart rate, the maximum rate of left ventricular pressure rise increased in non-failing hearts from 1388 +/- 86 to 1671 +/- 88 mmHg.s-1 (P < 0.01) and did not change in failing hearts. Ejection fraction decreased from 27 +/- 3% to 19 +/- 2% in patients with dilated cardiomyopathy (P < 0.05) when the pacing rate was changed from 84 +/- 2 beats.min-1 to 140 beats.min-1, which was associated with a significant increase in end-systolic volume without significant changes in end-diastolic volume.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8005116 TI - Release of chemoattractants and neutrophil activation in acute myocardial infarction immediately after successful recanalization of the infarct-related vessel by angioplasty. AB - The study investigated inflammatory responses in evolving myocardial infarction. Fifteen patients with acute myocardial infarction, who had undergone balloon recanalization of the infarct-related coronary artery within 4 h after onset of symptoms, were examined. Blood samples were obtained through the guiding catheter and from the pulmonary artery before and immediately after successful recanalization. After recanalization, plasma from the pulmonary artery was 47% (quartiles: 19%, 78%; P = 0.001) more chemotactic to neutrophils from normal donors than before recanalization. Furthermore, significant changes in neutrophil function were found in the pulmonary artery. Compared to the values before recanalization, the nitroblue tetrazolium score rose by 31% (quartiles: 4%, 37%; P = 0.003), FMLP-stimulated superoxide anion production by 10% (quartiles: 0%, 39%; P = 0.020), and chemotaxis by 46% (quartiles: 0%, 81%; P = 0.011), while neutrophil filterability decreased by 28% (quartiles: 15%, 47%; P = 0.010). No significant changes in neutrophil parameters were found in the arterial blood. The study indicates that chemoattractants are released in the early reperfusion period of evolving myocardial infarction. These chemoattractants may act as inflammatory mediators causing neutrophil activation. PMID- 8005117 TI - Oxidative stress in patients with unstable angina. AB - The aim of this study was to determine whether oxidative stress occurs in unstable angina. Thirty patients with unstable angina class B (Braunwald classification) were prospectively studied. Control groups consisted of 23 patients presenting with stable angina and of 21 age-matched healthy volunteers. Upon admission and every 8 h for 24 h, blood samples were drawn for the determination of plasma malondialdehyde (MDA) levels, Se-glutathione peroxidase (GPX) activity, erythrocyte reduced glutathione (GSH) concentrations, erythrocyte GPX and superoxide dismutase (SOD) activities. Coronary angiograms were performed within 4 days of admission in 26 out of the 30 patients included in the study. Nine of these 30 patients were subsequently identified as presenting a non-Q wave myocardial infarction and were separately examined. On admission, only plasma MDA levels and erythrocyte GSH concentrations differed among groups. Plasma MDA levels of patients presenting with unstable angina (P < 0.01) and acute myocardial infarction (P < 0.05) were higher than those of patients with stable angina and of normal volunteers, whereas there was no difference in these parameters between unstable angina and non-Q wave myocardial infarction groups. Erythrocyte GSH concentration was lower in all patient groups as compared to normal subjects. ANOVA for repeated measures showed no difference between admission and subsequent levels for all parameters. Finally, no difference was observed for any of the parameters when anti-ischaemic or anti-aggregant treatment before admission, or the number of affected vessels on coronary angiograms, were considered. We conclude that an oxidative stress can be evidenced in patients with unstable angina or acute myocardial infarction. PMID- 8005118 TI - Changes in the surface electrocardiogram during the onset of spontaneous ventricular fibrillation in man. AB - The aim of this study was to quantify electrocardiographic changes during the onset and early stages of ventricular fibrillation. Thirty recordings of ventricular fibrillation (mean duration 57 s, range 24-160 s) were obtained from 23 Coronary Care Unit patients. Each recording was investigated using frequency analysis on 1 s epochs of data. A significant rise in the mean dominant frequency of ventricular fibrillation from 3.9 Hz (SD 0.8 Hz) to 5.9 Hz (SD 1.0 Hz) was observed between 1 s and 30 s (P < 0.0001). At the same time, the width of the dominant peak decreased significantly (P < 0.001) and the height of higher frequency harmonics fell (P < 0.01). There was no significant change in peak height as ventricular fibrillation evolved. This study shows that the electrocardiogram retains periodic characteristics during the first 30 s of ventricular fibrillation and that these periodic characteristics become concentrated in a progressively narrower band of frequencies. These findings would suggest that during the early stages of ventricular fibrillation myocardial activation is both accelerating and coherent, rather than incoherent as has been traditionally believed. PMID- 8005119 TI - High-resolution and signal-averaged electrocardiography to separate post myocardial infarction patients with and without ventricular tachycardia. AB - High-resolution and signal-averaged ECG, 24 h Holter recording and ejection fraction were used to separate post-myocardial infarction patients with and without ventricular tachycardia (VT) among 150 individuals: 26 patients with an old myocardial infarction and documented sustained VT, 104 patients with an acute myocardial infarction without sustained VT, who were followed-up for 2 years, and 20 healthy volunteers. Bipolar orthogonal XYZ leads were recorded, high-pass filtered at cut-off frequencies of 25, 40, 60, 80 and 100 Hz, and combined to vector magnitude square root of X2 + Y2 + Z2. The filtered QRS duration, the root mean-square voltages of different time intervals and the durations of low amplitude signals under different thresholds, both from the initial and terminal QRS, were calculated. The sensitivity and specificity of each parameter alone and in every combination of two, three and four parameters (17 million different combinations) were computed both from non-averaged and averaged data. The best separation was achieved by 12 combinations all including four signal-averaged ECG parameters, with a sensitivity of 81% and a specificity of 79%. The parameters represented most were: filtered QRS duration at 25 Hz, RMS voltage of the last 50 ms at 25 Hz, terminal LAS duration at 80 Hz, and RMS voltage of the last 20 ms at 80 Hz. Parameters of the initial QRS complex did not improve either the sensitivity or the specificity of the method. In logistic regression analysis, the best combinations of four signal-averaged ECG parameters separated VT patients better (P < 0.001) than non-sustained ventricular tachycardia at Holter (P = 0.001); left ventricular ejection fraction (P = 0.01); or age (P = 0.006). Parameters calculated from averaged data gave better results than parameters calculated from non-averaged data. PMID- 8005120 TI - Catheter ablation of accessory pathways in children. AB - The efficacy and safety of catheter ablation of accessory pathways (AP) was studied in 79 children (age, 4-16 years), using DC shocks (n = 25) or radiofrequency energy (n = 54). All patients had documented arrhythmias including ventricular fibrillation in four. Organic heart disease was present in four patients. AP locations were left lateral (n = 36), posteroseptal (n = 36), right lateral (n = 8), Mahaim fibres (n = 2) and right anteroseptal (n = 6). Seven patients had multiple AP. One patient had a preexcitation which appeared secondary to an atrio-infundibular connection (Fontan procedure). The ablation site of concealed or overt AP was identified by retrograde or anterograde conduction mapping, respectively. A mean of 2.6 +/- 1 cathodal shocks (80-160 J) was delivered to 25 patients over 29 sessions, resulting in initial AP ablation in all. Fulguration was uncomplicated in all except in one patient (4%) who developed a secondary complete AV block post-ablation. During a follow-up period of 30-69 months, intermittent preexcitation recurred in two asymptomatic patients, but no significant tachycardia was inducible at late electrophysiological study, including under isoproterenol infusion. Radiofrequency energy was applied to 54 patients during 62 sessions, using 20-40 watts for 30-60 s. AP ablation was initially achieved in all patients using a median of three impulses, without significant immediate side-effects. Two patients (4%) developed a short episode of blurred vision possibly due to a microembolism. After discharge, the follow-up period was 10 +/- 5 months (range 1 to 24). All patients but one (98%) were asymptomatic without any drug therapy.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8005121 TI - Antihypertensive efficacy and tolerability of different drug regimens in isolated systolic hypertension in the elderly. AB - The pharmacological treatment, mainly based on diuretics, of isolated systolic hypertension (ISH) has recently been shown to reduce the risk of stroke and coronary heart disease in the elderly. The purpose of this study was to compare the antihypertensive effect and tolerability of different drug regimens in elderly subjects with ISH (systolic blood pressure--SBP-- > or = 160 mmHg and diastolic blood pressure--DBP-- < 90 mmHg). A multicentre, randomized, controlled open trial was planned in the general practice setting. Four widely used treatment schedules were tested: hydrochlorothiazide 25 mg plus amiloride 2.5 mg (H+Am), nifedipine slow release 20 mg (N), atenolol 50 mg (At) and atenolol 25 mg plus chlorthalidone 6.25 mg (At+C). After a baseline evaluation, 308 patients (76.3% female, mean age 75.3 +/- 7.1 years) were randomized and followed up for 6 months. After 3 months the drug dosage was doubled if the systolic blood pressure goal (SBP < 160 mmHg and SBP reduction of at least 20 mmHg) had not been reached. Ninety-four subjects (30.5%) presented contraindications to beta-blockers. At the 3rd- and 6th-month visits all treatment groups, except At, showed a significant reduction in SBP compared to the control group; DBP showed no significant reduction in any group at any time. At the end of the follow-up the percentage of hypertensives who had reached the BP goal was 14.6% in the control group, 52.9% in H+Am, 54.8% in N, 28.6% in At and 52.2% in At+C.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8005122 TI - Coronary angioplasty in patients 75 years and older; comparison with coronary bypass surgery. AB - From November 1988 to May 1992, 108 patients (79 men, 29 women) 75 years or older (mean 78 +/- 3, range 75-90 years) underwent coronary angioplasty (group I: n = 62) or coronary bypass surgery (group II: n = 46). Group II patients were younger (76 +/- 2 vs 79 +/- 4, P = 0.002) and had a higher proportion of multivessel disease. The two groups were comparable with regard to the presence of unstable angina, left ventricular ejection fraction and Q wave infarction. In-hospital mortality was similar in the two groups (6.4% vs 4.3%). Complete revascularization (72% vs 47%, P < 0.05) and left anterior descending artery revascularization (100% vs 45%, P < 0.01) were more frequent in group II. Two year infarction-free survival was similar (group I: 76 +/- 6%; group II: 79 +/- 6%) but recurrent class III or IV angina (36% vs 9%, P < 0.05) and repeat procedures (26% vs 0%, P < 0.05) were more frequent in group I. PMID- 8005123 TI - Gradient-echo magnetic resonance imaging during incremental dobutamine infusion for the localization of coronary artery stenoses. AB - Dobutamine pharmacological stress testing in conjunction with gradient-echo magnetic resonance imaging (MRI) may be a useful tool for the assessment of haemodynamically significant coronary artery stenoses. Therefore, 28 patients without previous myocardial infarction but significant proximal stenoses (> or = 70% diameter stenosis) of one or more coronary arteries were selected for dobutamine-MRI. Each patient underwent MRI at rest and during incremental dobutamine infusion (5, 10, 15 and 20 micrograms.kg-1.min-1). Additionally, all patients were submitted to exercise stress electrocardiography (EST). A total of 72 segments per patient obtained from identical short axis and transverse tomograms at rest and during dobutamine infusion were evaluated by two observers. Each segment was graded as normal, hypokinetic, akinetic or dyskinetic. Dobutamine-MRI was considered pathological if segmental wall motion deteriorated by at least one grade after dobutamine infusion. For comparison with coronary angiography, segmental wall motion gradings were related to the respective coronary artery territories. Peak rate-pressure product during steady-state dobutamine infusion (18.493 +/- 4.315 mmHg.min-1) was significantly lower (P < 0.01) than during EST (21.316 +/- 4.937 mmHg.min-1). Dobutamine-induced wall motion abnormalities were observed in 22/26 (85%) MR studies and 20/26 (77%) patients had a pathological EST. Regional asynergy induced by dobutamine-MRI occurred in 11/15 (73%) patients with single and 11/11 (100%) with multi-vessel disease. Sensitivity and specificity for the detection of a stenosed coronary artery were 87% and 100% for the left anterior descending, 62% and 93% for the left circumflex and 78% and 88% for the right coronary artery respectively.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8005124 TI - Comparison of two methods of determining renal perfusion with and without captopril pretreatment in groups of patients with left ventricular dysfunction. AB - Methods of effective renal plasma flow measurement by 125I-orthoiodohippurate elimination and para-aminohippurate clearance were compared with and without captopril pretreatment in 10 chronic heart failure patients and in 20 patients after transmural myocardial infarction. In the chronic heart failure group measurements of effective renal plasma flow by the two techniques were strongly correlated (r = 0.92, P < 0.00001), as was the captopril-mediated change in effective renal plasma flow by the two methods (r = 0.85, P = 0.002). However, in absolute terms para-aminohippurate clearance significantly exceeded 125I orthoiodohippurate clearance by a mean (+/- SD) of 24.8 +/- 43.7 ml.min-1 (P < 0.05) so that only using the former technique was a significant increment in renal perfusion observed in response to converting enzyme inhibition. In the post myocardial infarction group, correlations between the two methods were variable and much poorer than in the chronic heart failure group (r = 0.54, P = 0.01 and r = 0.74, P = 0.002 on consecutive days). Furthermore, captopril-mediated increments in effective renal plasma flow by the two techniques were unrelated (r = -0.19, P = 0.59). In this group 125I-orthoiodohippurate elimination significantly exceeded para-aminohippurate clearance (P < 0.05). This reversed association and the weaker relationships between methods in post-infarction as compared to chronic heart failure patients may be related to interference by thrombolytic or aspirin treatments. PMID- 8005125 TI - Vascular injury following cardiac catheterization, coronary angiography, and coronary angioplasty. AB - All vascular injuries occurring at this hospital department over a 5-year period (1987-91) as a result of cardiac catheterization, coronary angiography, or coronary angioplasty (PTCA) and requiring transfusion, surgical consultation, or repair, are reviewed. Such complications may occur late and, to detect cases not apparent from the protocol accompanying every examination, a questionnaire was sent to all surgical clinics in the region asking for details of vascular surgical intervention after angiography. The present review of 4879 examinations disclosed 18 patients with 19 vascular injuries (0.39%); four of them were detected by the questionnaire. The types of injury were: pseudoaneurysm (12), thrombembolic episode (4), and excessive bleeding (3). Of the patients with a vascular complication 11 (61%) were receiving anticoagulation treatment, compared to 10% in the whole series; two others suffered from a coagulopathic state. Catheterization was difficult or severe atherosclerosis was present in three, inadvertent mobilization occurred in one, and unintentional puncture distal to the common femoral artery occurred in two patients. With the increasing use of invasive diagnostic and interventional procedures in cardiovascular diseases, knowledge of the type and frequency of possible complications is important, especially of those that may occur late. In the present study anticoagulation, coagulation disorders, and cardiac catheterization combined with brachial puncture and angiography all predisposed to a vascular complication. PMID- 8005126 TI - Can anaerobic threshold be used as an end-point for therapeutic trials in heart failure? Lessons from a multicentre randomized placebo-controlled trial. The VO2 French Study Group. AB - Anaerobic threshold (AT), proposed as a non-invasive index of exercise tolerance, independent of patient motivation, is considered more reliable than exercise duration in assessing the effect of drug therapy in chronic heart failure (CHF). However, inter-observer variation in patients may be more difficult than in normal subjects. In a multicentre study, 85 patients from 10 centres performed a total of 331 bicycle maximal tests (ramp protocols, 10 watts.min-1) with respiratory gas analysis by different systems. A central committee reviewed all the tests. Percentages of AT determination ranged from 34% to 71% depending on the method used. Apart from the respiratory exchange ratio (RER) method, which yielded the lowest rate of determination: 34%, and the crossing point (when RER = 1), which yielded the highest rate, 71%, other methods of determination, such as carbon dioxide (42%), minute ventilation (52%) or ventilatory equivalents plotted vs time (57%), did not differ in the rate of AT determination. Thus, even among trained physicians, AT determination was not reliable. The crossing point may nevertheless be a valuable index from a pragmatic standpoint, although it occurs after the actual AT. Peak oxygen uptake should remain the main end-point in assessment of exercise capacity. PMID- 8005128 TI - Effects of ramipril on the neurohormonal response to exercise in patients with mild or moderate congestive heart failure. AB - Static measurements of plasma neurohormones at rest may not be adequate to detect alterations in cardiovascular control mechanisms in congestive heart failure (CHF). Therefore, it is of interest to study neurohormonal activation during different physiological conditions. Plasma neurohormones were measured in 54 patients on diuretic therapy for mild or moderate CHF. Samples were taken at rest and immediately after maximal bicycle exercise, before and after 12 weeks of treatment with ramipril or placebo. There was a strong correlation between the plasma levels of each hormone before and after exercise. An inverse correlation existed at baseline between exercise duration and angiotensin II levels after maximal exercise (r = -0.30, P = 0.03), but not at rest. Plasma levels of angiotensin II, aldosterone, atrial natriuretic peptide (ANP) and noradrenaline were increased after maximal exercise compared to rest. Plasma angiotensin converting enzyme activity and ANP were reduced by ramipril compared to placebo, both at rest and after exercise, but levels of angiotensin II, aldosterone and nordrenaline were not significantly affected. Thus, exercise consistently activates neurohormonal systems in patients with CHF. Patients with the lowest exercise duration had the highest angiotensin II levels after exercise. Measurements of plasma neurohormones after maximal exercise provide limited additional value to measurements at rest. PMID- 8005127 TI - Oral enoximone as a substitute for intravenous catecholamine support in end-stage congestive heart failure. AB - We performed a double-blind, placebo-controlled study to determine whether oral enoximone would aid weaning dobutamine-dependent patients. Twenty-four patients 64 +/- 10 years, with an echocardiographic ejection fraction of 0.20 +/- 0.06, and receiving maximal therapy were studied. After failure of dobutamine weaning, a dobutamine infusion was set up at 10 micrograms.kg-1.min-1 for 48 h. Oral enoximone (100 mg t.i.d.) or placebo was added from D0 for the next 28 days, while the dobutamine dosage was progressively decreased after D4 and eventually stopped at D7. The patients were then followed-up for 21 days (i.e. until enoximone administration had continued for 28 days). In the placebo group, two patients suffered a relapse of congestive heart failure (CHF) before D4, six patients withdrew during dobutamine tapering (five with a relapse of CHF and one with septic shock) and two during follow-up (one with a relapse of CHF and one with sustained ventricular tachycardia). In the enoximone group, three patients withdrew during dobutamine tapering (two with a relapse of CHF, one with a cutaneous rash). Four patients on placebo and nine receiving enoximone could be weaned from dobutamine, P < 0.05. Echocardiographic LV ejection fraction significantly increased and Doppler-derived indexes of systolic function tended to increase when enoximone but not placebo was associated with dobutamine. Oral enoximone might be helpful in weaning patients with end-stage congestive heart failure from i.v. dobutamine. PMID- 8005129 TI - Three-year follow-up of the Oxford Cholesterol Study: assessment of the efficacy and safety of simvastatin in preparation for a large mortality study. AB - We report the results of a randomized single-centre study designed to assess the effects of simvastatin on blood lipids, blood biochemistry, haematology and other measures of safety and tolerability in preparation for a large-scale multicentre mortality study. Six hundred and twenty-one individuals considered to be at increased risk of coronary heart disease were randomized, following a 2-month placebo 'run-in' period, to receive 40 mg daily simvastatin, 20 mg daily simvastatin or matching placebo. Their mean age was 63 years, 85% were male, 62% had a history of prior myocardial infarction (MI), and the mean baseline total cholesterol was 7.0 mmol.l-1. Median follow-up in the present report is 3.4 years. Eight weeks after randomization, 40 mg daily simvastatin had reduced non fasting total cholesterol by 29.2% +/- 1.1 (2.03 +/- 0.08 mmol.l-1) and 20 mg daily simvastatin had reduced it by 26.8% +/- 1.0 (1.87 +/- 0.07 mmol.l-1). Almost all of the difference in total cholesterol at 8 weeks was due to the reduction in LDL cholesterol (40.8% +/- 1.6 and 38.2% +/- 1.4 among patients allocated 40 mg and 20 mg of simvastatin daily respectively), but simvastatin also reduced triglycerides substantially (19.0% and 17.3%) and produced a small increase in HDL cholesterol (6.4% and 4.8%). These effects were largely sustained over the next 3 years, with 40 mg daily simvastatin producing a slightly greater reduction in total cholesterol at 3 years (25.7% +/- 1.9 reduction) than did 20 mg daily simvastatin (22.2% +/- 1.8). There were no differences between the treatment groups in the numbers of reports of 'possible adverse effects' of treatment or of a range of different symptoms or conditions (including those related to sleep or mood) recorded at regular clinic follow-up. Mean levels of alanine aminotransferase, aspartate aminotransferase and creatine kinase were slightly increased by treatment, but there were no significant differences between the treatment groups in the numbers of patients with significantly elevated levels. A slightly lower platelet count in the simvastatin group was the only haematological difference from placebo, with no difference in the numbers of patients with low platelet counts. In summary, the simvastatin regimens studied produced large sustained reductions in total cholesterol, LDL cholesterol and triglyceride and small increases in HDL cholesterol. They were well tolerated, with no evidence of serious side-effects during the first 3 years of this study.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8005130 TI - The prognostic significance of post-infarction angina pectoris and the effect of verapamil on the incidence of angina pectoris and prognosis. The Danish Study Group on Verapamil in Myocardial Infarction. AB - The prognostic significance of angina pectoris and the effect of intervention with verapamil on the incidence of angina pectoris were studied in patients recovering from myocardial infarction and included in the Danish Verapamil Infarction Trial II. During the second week after admission patients were doubly blindly randomized to treatment with verapamil 360 mg.day-1 or placebo. Treatment was continued for up to 18 months. At discharge angina pectoris was reported in 11% of 869 patients randomized to verapamil and in 12% of 888 randomized to placebo (ns). One month after discharge a significant increase in the prevalance of angina pectoris was reported in both the verapamil (33%) (P < 0.001) and the placebo groups (39%) (P < 0.001). The one month prevalence of angina pectoris (P = 0.03) and the 18 months overall incidence of angina pectoris (P = 0.002) were both significantly lower in the verapamil group compared with placebo. Stable angina pectoris during the first month of follow-up was a significant predictor of major events (i.e. death or reinfarction) (hazard ratio = 1.45; 95% confidence limits: 1.10, 1.89). As verapamil significantly reduced the incidence of angina pectoris during daily activities, and thereby the number of patients at high risk, the beneficial effect of verapamil in reducing major events in patients recovering from myocardial infarction is likely to be due to abolishing myocardial ischaemia. PMID- 8005131 TI - The role of elastic recoil after balloon angioplasty of rabbit arteries and its prevention by stent implantation. AB - Elastic recoil, neointima formation and vessel narrowing after balloon angioplasty or stent implantation were compared in 17 non-atherosclerotic New Zealand White rabbits. The implantation of a balloon-expandable Palmaz-Schatz stent was performed in one iliac artery and a balloon angioplasty alone was performed in the contralateral artery (n = 34 arteries). Quantitative histomorphometry was performed by a computer-assisted analysis 1 h and 4, 10 and 24 weeks after the initial procedure. The histological appearance of the neointima was similar to that of human restenosis. The amount of the neointima was increased within stented vessels as compared to balloon angioplasty alone (1.0 +/- 0.1 vs 0.4 +/- 0.1 mm2 at 4 weeks, P < 0.001). However, the neointimal lumen narrowing was smaller in the stented vessels due to persistent increase in vessel perimeter as compared to balloon angioplasty alone (16.5 +/- 0.9 vs 34.7 +/- 16.5% lumen narrowing at 4 weeks, P < 0.05). In conclusion, stent implantation enhances neointima formation as compared to angioplasty in non atherosclerotic rabbits. The prevention of elastic recoil after stent implantation, however, reduces the neointimal lumen narrowing. This study supports clinical observations demonstrating lower restenosis rates after stent implantation compared to standard balloon angioplasty. PMID- 8005132 TI - Adenosine-induced non-sustained polymorphic ventricular tachycardia. AB - Adenosine has become widely used because of its diagnostic and therapeutic value in the emergency management of arrhythmias. It produces transient heart block by slowing conduction through the AV node and thus terminates supraventricular tachycardias that involve the atrioventricular node. Bradyarrhythmias of short duration are common side effects of the use of this drug. Premature atrial and ventricular beats have also been reported. The very short half-life and lack of serious adverse effects generally lead to the consideration that adenosine is a safe drug. We describe a 56-year-old woman with a supraventricular tachycardia. To terminate this rhythm disorder intravenous adenosine was given. Interruption of the supraventricular tachycardia was followed by non-sustained polymorphic ventricular tachycardia. PMID- 8005133 TI - Evaluation of acute myocarditis and pericarditis by Gd-DTPA enhanced magnetic resonance imaging. AB - Gd-DTPA enhanced magnetic resonance imaging was performed in two adult patients with acute myocarditis and pericarditis. Gd-DTPA enhancement seemed to identify the exact cardiac region with the higher degree of inflammation. PMID- 8005134 TI - Double ventricular responses during extrastimulation of atrioventricular nodal reentrant tachycardia. AB - In patients with dual atrioventricular (AV) nodal pathways, double ventricular responses to a single atrial depolarization have been shown to occur, but virtually only during atrial pacing in sinus rhythm. We report on a patient with a slow-fast form of AV nodal reentrant tachycardia who exhibited double ventricular responses following extrastimulation during AV nodal reentrant tachycardia. The phenomenon of double ventricular responses during the tachycardia was demonstrated by extrastimulation from the proximal coronary sinus. Retrograde unidirectional block in the slow pathway, and an anterograde effective refractory period that was shorter in the fast pathway than that in the slow pathway, are suggested. PMID- 8005135 TI - Initiation of ventricular fibrillation by atrial fibrillation. AB - We report the case of a patient who developed spontaneously a ventricular fibrillation during atrial fibrillation, 8 min after a perfusion of isoproterenol was stopped. Two mechanisms could explain the ventricular arrhythmia: silent ischaemia and a long-short cycle sequence just before ventricular fibrillation. PMID- 8005136 TI - Fallopian tube cancer metastatic to the breast. AB - The breast is an infrequent site of metastatic disease from a primary genital tract malignancy. A case of fallopian tube carcinoma metastasizing to the breast is presented. A solitary metastasis must be distinguished from the primary breast cancer as the treatment and prognosis are quite different. The pathologic diagnosis of metastatic carcinoma to the breast may be difficult if the tumor is poorly differentiated type. PMID- 8005137 TI - Laparoscopic prophylactic oophorectomy in women belonging to ovarian cancer-prone families. Advantages and shortcomings. AB - Laparoscopic prophylactic oophorectomy was performed on four women who belonged to ovarian cancer prone families. The procedure was of short duration with an uncomplicated intra- and postoperative course and required only brief hospitalization. These merits may outweigh those of prophylactic oophorectomy performed by laparotomy during which hysterectomy is usually also performed. When prophylactic oophorectomy is contemplated, operative laparoscopy should also be considered. PMID- 8005138 TI - GnRH analogs in benign breast disease and breast cancer chemoprevention. A challenge for the year 2000. AB - GNRH analogs (GNRHAs) are currently used in the treatment of prostatic and breast cancer and in several benign gynecological conditions. Because of their ability to suppress sex hormone secretion and the supposed role of these hormones in the physiopathology of fibrocystic mastopathy, GNRHAs have been proposed for the management of severe breast pain and nodularity. In preliminary studies the treatment with GNRHAs for 3-6 months improves clinical and radiologic manifestations of mastopathy, also when breast pain has been recurrent or refractory to other hormonal drugs. Further studies are required to determine the optimal length of treatment and the adverse effects induced by estrogen deficiency in premenopausal women. There is evidence that an early menopause reduces woman's lifetime risk of breast cancer. According to this data, a high dose GNRHAs regimen associated with estrogen replacement therapy (ERT) has been proposed as chemopreventive agent for premenopausal women at high risk of breast cancer. The definition of the long term effects of GNRHAs on bone and lipid metabolism is essential before a large trial of chemoprevention can be carried out. PMID- 8005140 TI - Metastatic malignant melanoma of the ovary. Case report. PMID- 8005139 TI - Pre-operative staging of endometrial carcinoma: magnetic resonance imaging versus ultrasounds and hysteroscopy. AB - Ultrasound, hysteroscopy and magnetic resonance imaging has been considerated to assess the loco-regional or extrapelvic extension of the endometrial carcinoma. Sonography has demonstrated a certain inaccuracy in predicting myometrial invasion or the involvement of the canal. Hysteroscopy allows us to characterize neoplasia and to assess its extension in the cervical canal. MR imaging is more helpful in the diagnosis of channel invasion. The assessment of ovarian metastasis requires ultrasonography or coronal planes RM imaging. As regards the involvement of the pelvic and extrapelvic lymph nodes MR is more accurate than ultrasound scan. PMID- 8005141 TI - Hysteroscopy may transport malignant cells into the peritoneal cavity. Case report. AB - The purpose of this report is to caution against the use of hysteroscopy at the time of uterine curettage performed in women with postmenopausal bleeding suspected of having endometrial carcinoma. A 63 year old postmenopausal woman had endometrial carcinoma diagnosed by hysteroscopically guided curettage. At the time of hysterectomy three weeks later, malignant cells were found in pelvic washings. Although a causal relationship between hysteroscopy and malignant peritoneal cytology cannot be postulated, we believe that hysterescopy should be used with caution in the work up of postmenopausal bleeding. PMID- 8005142 TI - The association of ovarian dysgerminoma and gonadoblastoma in a phenotypic female with 46 XY karyotype. AB - Dysgerminoma is the most common malignant germ cell tumor of the ovary. It can be found either in a pure form or mixed with other germinal elements. It has also been reported arising from gonadoblastoma, which may be regarded as an in situ germ cell malignancy. We describe the case of an 18-year-old patient who had a dysgerminoma arising from the left ovary and a gonadoblastoma replacing the right ovary. She was a nonvirilized phenotypic female, with 46, XY genotype. The patient underwent bilateral salpingo-oophorectomy with total hysterectomy, appendicectomy, infracolic omententectomy, selective pelvic and para-aortic lymphadenectomy, peritoneal random biopsies. The surgical-pathological stage of dysgerminoma was retroperitoneal stage III. The patient received postoperative radiotherapy on the whole pelvis and para-aortic lymph nodes and precautional radio therapy on the mediastinum and supraclavicular lymph nodes. She is currently alive with no evidence of disease after 46 months from surgery. PMID- 8005143 TI - Adjunctive radiotherapy after radical hysterectomy in high risk early stage cervical carcinoma. Assessment of morbidity and recurrences. AB - Morbidity and prognostic factors were reviewed in 145 patients who underwent radical hysterectomy and pelvic lymphadenectomy for invasive cervical cancer between January 1976 and December 1986. Ninety five patients received adjuvant postoperative external radiotherapy (average 4800 cGY). One hundred twenty patients were F.I.G.O. stage IB, and 25 were clinical stage IIA. Indications for adjuvant radiotherapy included 3 categories of patients with high risk factors: 1) pelvic lymph node metastases, 2) parametrial invasion and/or surgical margins involvement, 3) large volume, deep stromal penetration or uterine extension. Four percent of the patients suffered major gastrointestinal complications, 8.9% had major genito-urinary complications, 19 patients had lymphocytes and 2 patients complained of thromboembolic episodes. Of the 19 patients with major gastrointestinal or genito-urinary morbidity, 7 (38.8%) were related to radiotherapy. Thirty-nine patients had node involvement, 38 of these patients received radiotherapy and 5-year survival rate was 43.5% versus 87.7% in other cases (p < 0.001). Of the 14 patients with parametrial invasion and/or surgical margins involvement, 10 received radiotherapy and overall 5-yrs survival was 85.8%. Of the 37 patients related to third category of risk, 18 received adjuvant radiotherapy with 83.3% 5-yrs survival versus 94.7% of other 19 cases (n.s.). Patients treated with surgery alone had a better 5-yrs survival (96%) than those who received combination therapy (66.3%) (p < 0.001). Adjuvant radiotherapy increases the morbidity of radical hysterectomy, while it has a relative value in preventing local and distant recurrences. In view of reduced survival in high risk patients with node involvement, consideration should be given to adjuvant systemic chemotherapy in high risk cases. PMID- 8005144 TI - Mixed ovarian neoplasm composed of struma ovarii and Brenner tumour. Report of a case. AB - The case is reported of a patient with a mixed lesion composed of struma ovarii and Brenner tumour. This is an extremely rare tumour and only two well documented cases were found in the English literature. PMID- 8005145 TI - Cyto-histological aspects of chorionepithelioma in fluorescence. AB - The Author illustrates cytochemical and histochemical pictures of the chorion epithelioma, which the fluorochromization with orange acridine, according to the Bertanlanffy's method, gives with extreme clearness. The intense colouring of both nucleic acids, DNA and RNA indicates a lively functional activity and elevated trophism of the trophoblastic cells. PMID- 8005146 TI - Primary carcinoma of the fallopian tube: a study of 8 cases. AB - Eight patients with primary tubal carcinoma of the fallopian tube are presented. These patients constituted 0.3% of all gynecological malignancies encountered during the period the study was conducted. The most common symptom was abnormal vaginal bleeding (4 patients). All patients but one had extra tubal disease at the time of surgery. No patient was operated with a preoperative diagnosis of tubal cancer. All patients were subjected to primary surgical therapy. As adjuvant therapy, radiotherapy (3 patients) and chemotherapy (5 patients) were given. Only three patients are living with a mean survival of 30 months. PMID- 8005147 TI - Squamous carcinoma of the cervix metastatic to the umbilicus. Case report. AB - Sister Joseph's nodule is a rare feature of advanced cervical carcinoma. This case is reported from a Nigerian teaching hospital where over 100 new cases of cervical carcinoma are seen annually. PMID- 8005148 TI - Surgical and psychosexual outcome following vaginal reconstruction with pelvic exenteration. AB - The improved prognosis with pelvic exenterative surgery for gynecologic malignancies has resulted in increasing concern for quality of life. Sexual dysfunction is a common sequel to pelvic exenteration and vaginal reconstruction should be considered in all these patients. This case review assesses our experience with three flap techniques for neovaginal construction. Medical charts were reviewed and survivors interviewed. Fourteen patients had vaginal reconstruction with gracilis myocutaneous (n. = 5), bulbocavernosus (n. = 3) or pudendal thigh fasciocutaneous (n. = 6) flaps at the time of pelvic exenteration. Partial or incomplete necrosis occurred in four (24%) and one (7%) patient had complete flap necrosis bilaterally, followed by an entero-vaginal fistula. Two patients developed recto-vaginal fistula in association with a low rectal reanastomosis (n. = 2) and tumor recurrence (n. = 1). Eight patients, seven of whom agreed to an interview and physical examination, are alive at a median of 15.5 months following pelvic exenteration. Three have stenotic and/or foreshortened vaginas. Two patients are apareunic by choice, four have discontinued vaginal intercourse because of dyspareunia and only one patient has satisfactory coitus. Other problems include vulvar pain (n. = 3), vaginal discharge (n. = 3), neovaginal hair growth (n. = 5) and protrusion of flaps (n. = 3). The functional results in this series are disappointing and better methods of vaginal reconstruction should continue to be developed. Patients undergoing neovaginal reconstruction at the time of pelvic exenteration require careful preoperative counselling and ongoing support after surgery with special attention to sexual dysfunction. PMID- 8005149 TI - Endometrioid carcinoma of the ovary. A clinicopathological study of 17 cases. AB - Seventeen patients with endometrioid carcinoma of the ovary were studied in order to establish clinical, surgical and histological prognostic factors. Disease recurred in 7 cases (41%) and statistically correlation was found between presence of ascites above 200 ml, advanced stage of the disease, low level of cellular differentiation and peritoneal disease and/or a residual tumour after surgery. No correlation was found between age at presentation, menopausal status, size of tumour or bilaterality. The estimated survival rate for 5-years was placed between 40%-50%. Pathological study found associated endometrioid disease in 3 cases (20%) (2 adenocarcinomas, 1 hyperplasia with atypias), and ovarian endometriosis in 2 cases (12%). Furthermore, two extremely rare cases are reported: clinical presentation of paraneoplastic dermatomiositis and recurrence at the laparoscopic puncture site. PMID- 8005150 TI - Viability as seen with radiolabelled fatty acids--a new approach to a challenging problem. PMID- 8005151 TI - Relationship between blood flow and fatty acid metabolism in subacute myocardial infarction: a study by means of 99mTc-Sestamibi and 123I-beta-methyl-iodo-phenyl pentadecanoic acid. AB - Contradictory data have been published on the relative behaviour of fatty acids and flow tracers during the subacute stage of myocardial infarction. Therefore, the present study was set up (1) to investigate the potential occurrence of mismatches between beta-methyl-iodo-phenyl pentadecanoic acid (BMIPP), a fatty acid analogue, and Sestamibi, and to describe their nature, and (2) to relate these mismatches to clinical characteristics such as whether or not thrombolysis or percutaneous transluminal coronary angioplasty (PTCA) had been performed. Twenty-six patients were studied within 2 weeks after myocardial infarction. Sestamibi and BMIPP single-photon emission tomography (SPET) were performed within 4 days of one another. Activity of both tracers was scored in 16 basal, 16 midventricular and 8 apical segments, using a four-point grading system: 3 = normal (> or = 65% of maximum activity), 2 = mildly decreased (45%-64%), 1 = moderately decreased (25%-44%), 0 = severely decreased (0%-24%). Coronary arteriography was obtained during the same hospital stay. Four hundred and seventy-seven segments out of 1040 studied were abnormal for at least one tracer: 197 with higher Sestamibi activity (group I), 226 with equal scores for Sestamibi and BMIPP (group II) and 54 with higher BMIPP activity (group III). Seventy-five percent of group I segments and 84% of group III segments were found in infarct related artery territories. Group I segments were associated with acute thrombolysis and/or PTCA (P < 0.01), and with the absence of prior infarction in the territory of the infarct-related artery (P < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8005152 TI - Glucose metabolism in relation to perfusion in patients with ischaemic heart disease. AB - In order to correlate myocardial perfusion and residual metabolism in patients with coronary artery disease, the regional metabolic rate of glucose (rMRGlu) was compared with regional perfusion under glucose loading state (GL) and fasting state (FA). Fluorine-18 deoxyglucose dynamic scan was obtained in ten patients after oral GL and in 16 patients under FA. rMRGlu in seven segments was calculated using Patlak graphic analysis for comparison with normalized percent uptake of nitrogen-13 ammonia at rest in each segment. When perfusion was less than 45%, no segment showed an increase in rMRGlu (> or = 0.3 mumol/min/g) under either FA (0/6 segments) or GL (0/8 segments), indicating a certain threshold of perfusion for maintenance of glucose metabolism. When perfusion exceeded 45%, rMRGlu was higher in GL (0.37 +/- 0.18 mumol/min/g) than FA (0.15 +/- 0.12 mumol/min/g, P < 0.001) but there was very wide scatter of rMRGlu values under both states. Thus, both myocardium with preserved and myocardium with reduced glucose metabolism may exist when the perfusion exceeds 45%. In conclusion, a minimum threshold of perfusion for the maintenance of glucose metabolism may exist under both FA and GL. Below the threshold, irreversible damage may occur in the myocardium. Above the threshold, quantitative analysis of glucose metabolism should play an important role in differentiating reversibly injured myocardium from necrotic myocardium. PMID- 8005153 TI - Fluorine-18 deoxyglucose uptake in sarcoidosis measured with positron emission tomography. AB - Regional pulmonary glucose metabolism (MRglu; mumol h-1 g-1), extravascular lung density (D(EV); g cm-3) and vascular volume (VB; ml cm-3) were measured in a single midthoracic transaxial slice (approximately 2 cm thick) using position emission tomography (PET) in seven patients with histologically proven sarcoidosis. The measurements were repeated 1-7 months later after steroid therapy (in two cases, no treatment) in order to assess MRglu as an index of inflammation and relate it to routine pulmonary function tests, chest radiography and serum angiotensin converting enzyme (SACE) levels. MRglu was computed from serial lung scans and peripheral venous blood samples for 60 min following an i.v. injection of 18F-2-fluoro-2-deoxy-D-glucose (18FDG). Both MRglu (which was increased in six of seven patients) and elevated SACE levels returned to normal in those patients treated with high-dose steroids. Regional vascular volume was normal in six of seven cases and did not change significantly with therapy. The high tissue density measured in all patients decreased significantly in two of three patients treated with 40 mg prednisolone daily. The abnormal MRglu observed in active sarcoidosis becomes normal pari passu with SACE levels during high-dose steroid therapy. We conclude that MRglu measured with 18FDG and PET may reflect "disease activity" in sarcoidosis in quantitative terms (per gram lung tissue) and in respect of disease distribution. PMID- 8005154 TI - A multi-institutional study of interobserver agreement in the evaluation of dementia with rCBF/SPET technetium-99m exametazime (HMPAO). AB - Although specific patterns of technetium-99m exametazime [99mTc hexamethylpropylene amine oxime (HMPAO)] brain single-photon emission tomography (SPET) uptake have been described for patients with dementia, no multi institutional study has evaluated interobserver agreement. Interobserver agreement for 99mTc-HMPAO brain SPET uptake patterns in 50 clinically diagnosed demented subjects from four institutions were studied. Neurologists classified these subjects as presumed Alzheimer's disease (n = 21), confirmed Alzheimer's disease (n = 10), multi-infarct dementia (n = 9), HIV-related dementia (n = 7), or "mixed" (n = 3). In addition 20 normal (five per institution) 99mTc-HMPAO studies were included in a randomized blinded evaluation by three readers each from a different institution. Readers classified the general appearance of the images in one of four categories: normal, globally decreased uptake, focal areas of decreased uptake, and patchy changes in uptake. Consensus results show a sensitivity of 72% and specificity of 79% for identifying abnormalities in scans of demented subjects. Readers also rated 99mTc-HMPAO uptake in eight designated regions in each hemisphere. Significant reader agreement (P < 0.01) for the classification by general appearance and the ratings of regional uptake was obtained. This study demonstrates that interpretation of regional cerebral blood flow/SPET images is concordant across multiple institutions and readers. PMID- 8005155 TI - Pre-targeted immunodetection in glioma patients: tumour localization and single photon emission tomography imaging of [99mTc]PnAO-biotin. AB - The imaging of cerebral gliomas with radiolabelled monoclonal antibodies (MoAbs) has been previously reported. However, previous studies have been hampered by the drawback of a low tumour to non-tumour ratio. In order to overcome this problem we have developed a three-step pre-targeting method using the avidin-biotin system. The rationale of this technique consists in vivo labelling of biotinylated MoAbs targeted onto tumour deposits, when most of the unbound antibodies have been cleared from the bloodstream as avidin-bound complexes. The anti-tenascin MoAb BC2, specific for the majority of gliomas, was biotinylated and 1 mg was administered i.v. in 20 patients with histologically documented cerebral lesions. After 24-36 h, 5 mg avidin was injected i.v. followed 24 h later by a third i.v. injection of 0.2 mg PnAO-biotin labelled with 15-20 mCi technetium-99m. No evidence of toxicity was observed. Whole-body biodistribution was measured at 20 min, 3 h and 5 h post-injection. [99mTc]PnAO-biotin had a fast blood clearance and was primarily excreted through the biliary system. A dedicated single-photon emission tomography system was used to acquire brain tomographic images 1-2 h after the administration of [99mTc]PnAO-biotin. Tumours were detected in 15/18 glioma patients with a tumour to non-tumour ratio of up 14:1. This three-step method, based on the sequential administration of anti tenascin MoAb BC2, avidin and [99mTc]PnAO-biotin, can support computed tomography or magnetic resonance imaging for the diagnosis and follow-up of patients with glioma. Further studies are required to evaluate the potential of this technique for therapeutic application. PMID- 8005156 TI - Measurement of the ratio of glomerular filtration rate to plasma volume from the technetium-99m diethylene triamine pentaacetic acid renogram: comparison with glomerular filtration rate in relation to extracellular fluid volume. AB - Individual kidney glomerular filtration rate (IKGFR) can be measured from the renogram from the rate of uptake of technetium-99m diethylene triamine penta acetic acid (99mTc-DTPA). A blood sample is required to derive IKGFR in millilitres per minute, which is then usually normalised to body surface area. We describe a technique which does not require a blood sample, is already normalised for plasma volume and uses the robust Patlak plot for measuring renal uptake. The rate of kidney uptake, dR(t)/dt, at time = 0, as a fraction of the injected dose, is equal to the fraction of the plasma volume (PV) filtered per minute, i.e. IKGFR/PV. The gradient dR(0)/dt cannot be accurately measured directly but is equal to [alpha .LV(0)], where alpha is the renal uptake constant (proportional to IKGFR) and LV is the count rate over a left ventricular ROI. LV(0) was obtained by extrapolation of LV(t), while alpha is the slope of the Patlak plot up to 3 min. GFR/PV (i.e. right plus left kidneys) in patients with normal renal function was about 0.04 min-1, as would be expected from normal values of GFR (120 ml/min) and plasma volume (3 l). GFR/PV correlated significantly with the ratio of GFR to extracellular fluid volume (ECV), measured from the terminal exponential of the plasma clearance curve (GFR/PV = 3.2.GFR/ECV + 5.3 ml/min/l [r = 0.82, n = 82]). GFR/PV (r = 0.74) and GFR/ECV (r = 0.82) both correlated inversely and non-linearly with plasma creatinine in 43 studies where the measurement was made within 1 week of the 99mTe-DTPA study.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8005157 TI - Evaluation of copper(II)-pyruvaldehyde bis (N-4-methylthiosemicarbazone) for tissue blood flow measurement using a trapped tracer model. AB - Copper(II)-pyruvaldehyde bis (N-4-methylthiosemicarbazone) (Cu-PTSM) labelled with 62,64Cu is a promising radiotracer for the study of blood flow using positron emission tomography (PET). We have investigated the application of a simple trapped tracer model to measurements of tissue 64Cu-PTSM uptake combined with continuous arterial sampling. A dual-tracer method was used to compare blood flow estimated by 64Cu-PTSM with values derived from measurements using cobalt-57 microspheres in the rat. Prolonged retention of 64Cu-PTSM following intravenous administration was initially confirmed in both normal tissues and tumours. After intraventricular 64Cu-PTSM infusion, cumulative arterial 64Cu activity increased progressively, and after extraction in n-octanol was found to plateau to levels corresponding with those reached following administration of 57Co microspheres. Rapid and species-dependent rates of 64Cu-PTSM decomposition to non-extractable 64Cu complexes were found in rat and human blood in vitro (70% +/- 6% and 43 +/- 5% respectively at 16 min), demonstrating the need for immediate processing of arterial samples. Close agreement was found between blood flow estimated by 64Cu PTSM and 57Co microsphere methods in tissues of low to moderate flow: muscle (0.01, 0.08, 0.07 ml/min per gram; mean difference, mean 64Cu, mean 57Co), brain (0.09, 0.52, 0.43 ml/min per gram) and kidney (-0.16, 2.29, 2.45 ml/min per gram). Estimates of cardiac output also compared favourably between the two methods (5.7, 59.8, 54.1 ml/min). We conclude that a simple tissue trapping model may be suitable for the derivation of blood flow estimates using 62,64Cu-PTSM, PET imaging and continuous arterial blood sampling. PMID- 8005158 TI - Technetium-99m human immunoglobulin scintigraphy in psoriatic arthropathy: first results. AB - Standard bone scintigraphy [using technetium-99m methylene diphosphonate (MDP)] is widely held to be the most sensitive method for the early detection of psoriatic arthropathy. Preliminary results of this study reveal that 99mTc human immunoglobulin (HIG) scintigraphy demonstrates a typical premature pattern of extradermal psoriatic disease in digits indicative of the early stage of psoriatic arthritis. This pattern was also found in a rare case of psoriatic arthropathy without skin lesions. 99mTc-HIG scintigraphy appears to reveal the initial inflammatory characteristics of later bone lesions. In the advanced stage of psoriatic arthritis, 99mTc-MDP and 99mTc-HIG scans were found to be equally sensitive in the detection of the affected joints. Thus 99mTc-HIG scintigraphy seems to be useful in the early detection of psoriatic arthropathy and also in advanced psoriatic arthritis, as well as for the detection of psoriatic arthropathy without skin lesions. PMID- 8005159 TI - Positron emission tomography shows high specific uptake of racemic carbon-11 labelled norepinephrine in the primate heart. AB - (-)-Norepinephrine is the predominant neurotransmitter of the sympathetic innervation of the heart. Racemic norepinephrine was labelled with carbon-11 and injected i.v. into Cynomolgus monkeys. Five minutes after injection there was a more than tenfold higher radioactivity in the heart than in adjacent tissue. Pretreatment with the norepinephrine reuptake inhibitor desipramine reduced the uptake by more than 80%. The high specific uptake of racemic [11C]norepinephrine indicates that enantiomerically pure (-)-[11C]norepinephrine has promising potential for detailed mapping of the sympathetic innervation of the human myocardium. PMID- 8005160 TI - Drug interactions with radiopharmaceuticals. AB - Considerable information on documented drug and radiopharmaceutical interactions has been assembled in a tabular form, classified by the type of nuclear medicine study. The aim is to provide a rapid reference for nuclear medicine staff to look for such interactions. The initiation of drug chart monitoring or drug history taking of nuclear medicine patients and the reporting of such events are encouraged. PMID- 8005162 TI - Technegas: particle size and distribution. PMID- 8005161 TI - Review of imaging techniques for the diagnosis of breast cancer: a new role of prone scintimammography using technetium-99m sestamibi. AB - Imaging techniques currently used for the diagnosis of breast cancer are reviewed and compared. Besides mammography, magnetic resonance imaging, positron emission tomography, and thallium-201 scintimammography, a new role of technetium-99m sestamibi scintimammography is discussed. It is concluded that while mammography remains the procedure of choice in screening asymptomatic women for breast cancer, other imaging methods play an important role in detecting malignancies in symptomatic patients. 99mTc-sestamibi scintimammography has high sensitivity and improves the specificity of conventional mammography for the detection of breast cancer; with this technique, prone imaging is preferable to supine imaging. 99mTc sestamibi scintimammography thus deserves further study as a screening technique. PMID- 8005163 TI - Iodoheptadecanoic scintigraphy is not related to lipid turnover. PMID- 8005164 TI - Tracer imaging in lung cancer. PMID- 8005165 TI - Pulmonary embolism diagnosis: PIOPED and beyond. PMID- 8005166 TI - Effects of thromboxane A2 synthetase inhibitor (CV-4151) on reperfused skeletal muscle in rats. AB - To clarify the role of thromboxane A2 synthetase inhibitor (CV-4151) in the ischemia-reperfusion injury, the effect of CV-4151 was investigated in the gastrocnemius muscles of female Lewis rats. All tissues except femoral vessels were transected at the midthigh level and 4 h of ischemia was induced by vascular clamping of the femoral artery and vein, followed by 1 h of reperfusion. The sham group (n = 8) underwent the operation without ischemia-reperfusion; the control group (n = 8) with ischemia-reperfusion, and the CV-4151 group (n = 8) was pretreated with CV-4151 20 mg/kg. Skeletal muscle blood flow was measured by a hydrogen gas clearance method; the blood flow restored fully in the CV-4151 group, while it remained significantly low in the control group after 1 h of reperfusion (p < 0.05). Tissue levels of adenosine triphosphate (ATP) and creatine phosphate (PCR) were measured after 1 h of reperfusion; ATP decreased to 25% of nonischemic values in the control group. In contrast, premedication with CV-4151 significantly improved the recovery of ATP (p < 0.01). PCR showed the same tendency as ATP; CV-4151 also improved the recovery of PCR significantly (p < 0.05), but CV-4151 did not prevent the production of lipid peroxides. Serum thromboxane B2 was determined by radioimmunoassay; in the sham and the CV-4151 group the level was significantly lower than in the control group (p < 0.05). was significantly lower than in the control group (p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8005167 TI - Studies on the release of tissue kallikrein in experimental pancreatitis in the pig. AB - The activation of the kallikrein-kinin system is thought to be one of the pathophysiological factors in acute pancreatitis. A radioimmunoassay for porcine, pancreatic tissue kallikrein was developed and used to measure levels in normal plasma and peritoneal fluid and in experimental, bile-induced (group A) and bile trypsin-induced (group B) acute pancreatitis in the pig. Normal porcine plasma and peritoneal fluid contained about 2.17 +/- 0.11 and 1.91 +/- 0.19 microgram/l (SEM) tissue kallikrein, respectively. In experimental, acute pancreatitis there was a rapid rise in the plasma level of tissue kallikrein, followed by a slow increase to a final value of about 150% of the normal plasma level in both groups. In the peritoneal exudate a large increase (200-fold in group A and 2,000 fold in group B) in tissue kallikrein was seen, with a maximum within about 1/3 of the survival time, followed by a slow decrease until death in group B. In group A a smaller second peak was seen at about 2/3 of the survival time. Gelfiltration of peritoneal exudates showed complexes with alpha 1-, alpha 2 macroglobulin (alpha 1 alpha 2-M), and alpha 1-proteinase inhibitor (alpha 1-PI) and a large portion of free tissue kallikrein. The complexes with alpha 1 alpha 2 M and the free tissue kallikrein were found to be enzymatically active when tested on chromogenic tripeptide substrate. The presence of large amounts of free and active tissue kallikrein in the peritoneal exudate leads us to the conclusion that tissue kallikrein may be a major cause of local release of kinins in acute pancreatitis. PMID- 8005168 TI - Failure of adenine nucleotide and water content of cold-stored rat livers to serve as graft viability indices for transplantation. AB - A study was undertaken to determine whether the cellular viability of the liver graft and posttransplantation outcome could the assessed by the graft energy status or change in water content prior to the transplantation procedure. These measurements were performed in a rat liver transplantation model. In a first set of experiments, the time for 50% survival of grafts preserved with UW solution or saline solution was determined. Grafts preserved with UW solution could be cold stored for 19.9 h and grafted with a 50% success rate. The corresponding figure for saline-preserved grafts was 6.2 h. The energy status and water content of liver grafts preserved with UW solution for 19.9 h and livers preserved with saline solution for 6.2 h were compared. There were significant differences between livers preserved with UW solution and saline solution for ATP (p < 0.01), total adenine nucleotides (p < 0.05), ATP/ADP (p < 0.05) and energy charge levels (p < 0.05). ATP concentrations in the donor livers did not decrease significantly during cold storage when the success rate decreased from 100 to 0% after liver transplantation. The livers preserved with NaCl solution took up water during preservation. In contrast, the water content was reduced slightly in the livers preserved with UW solution and the differences were significant at all times. During cold storage using either the UW solution or saline solution for preservation, there were no significant time-related changes in the water content of the liver graft when the posttransplantation success rate decreased from 100 to 0% after liver transplantation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8005169 TI - Myocardial protection with Bretschneider cardioplegic solution--an evaluation of full oxygenation. AB - In the present study the effect of oxygenated Bretschneider cardioplegia on high energy phosphates [adenosine triphosphate (ATP), adenosine diphosphate (ADP) and creatine phosphate (CP)] and hemodynamics was evaluated in the isolated working rabbit heart. Hearts were obtained from 37 adult white Elco rabbits (3,100 +/- 110 g). After a 20-min working period 14 hearts were arrested with Bretschneider cardioplegia (8 degrees C) oxygenated with 98% oxygen (O2) and 2% carbon dioxide in comparison to 14 hearts receiving Bretschneider solution saturated with 98% nitrogen (N2) and 2% carbon dioxide as a control group for either 60 or 90 min (O(2)60, O(2)90, N(2)60, N(2)90 groups, n = 7). Seven hearts were used to determine preischemic baseline values of ATP, ADP and CP, 2 were excluded. The results showed a significantly poorer preservation of high-energy phosphates in hearts receiving oxygenated Bretschneider cardioplegia as compared to hearts receiving nitrogenated cardioplegia (p < 0.05). Postischemic recovery of hemodynamics did not demonstrate any statistically significant differences between the groups. However, the intragroup analysis showed a tendency towards weaker hemodynamic recovery in hearts treated with oxygenated cardioplegia. in contrast to the beneficial effect of oxygenated St. Thomas solution. In conclusion our findings suggest that oxygenated Bretschneider cardioplegia leads to significantly poorer preservation of high-energy phosphates and depressed hemodynamic recovery. PMID- 8005170 TI - Intramucosal pH changes following complete segmental small intestinal ischemia, as compared with the effects of superior mesenteric artery occlusion. AB - Microcirculatory nonperfusion of the intestinal mucosa may result in a subsequent prolongation of tissue ischemia, even after restoration of the mesenteric blood flow. It was hypothesized that there is a relationship between mucosal no-reflow and the amount of previously ischemic tissues during intestinal ischemia reperfusion. Accordingly, an examination was made of the changes in intestinal and gastric intramucosal pH (pHi) in dogs after a 120-min complete occlusion of the superior mesenteric artery (SMA) and those observed following ischemia of an ileal segment only. pHi, as an indicator of the adequacy of mucosal microcirculatory perfusion, was calculated by the tonometer technique. Baseline values of intestinal pHi (mean 7.25 +/- 0.12) and gastric pHi (mean 7.23 +/- 0.27) were determined in sham-operated animals. The 120-min intestinal ischemia caused a progressive fall in intestinal pHi to a mean value of approximately 6.8. Reperfusion resulted in a slow return to nearly normal pHi levels in the ileal segment, but essentially no intestinal pHi elevation was observed during the 90 min period following occlusion of the SMA. The gastric pHi remained at the control level during segmental intestinal ischemia reperfusion, but declined below the normal range following release of the occlusion of the SMA. It is proposed that continuing microcirculatory nonperfusion could explain the failure to demonstrate a postreperfusion elevation of pHi following complete occlusion of the SMA. PMID- 8005171 TI - Study of the electrical and mechanical activity of the rectum: an experimental study. AB - The electrical activity of the rectal detrusor was studied in 13 dogs. 10 electrodes were sutured serially to the rectal and lower sigmoid colon serosa. Electrical activity was recorded for 30 min/day for 10 days. Simultaneous electric and mechanical activity (recorded by a 6-French catheter connected to a pressure transducer) was also recorded with and without rectal distension by a condom balloon. Electrical activity was further determined after annular myotomy performed at different levels in the rectum and lower sigmoid colon. Pacesetter potentials (PP) were recorded from electrodes 3-10. They were triphasic, propagated caudally and had the same frequency and regular rhythm by all electrodes distal to the 3rd one. Frequency was constant in each dog from day to day. PP were accompanied by action potentials (AP) which had inconsistent frequencies and were accompanied by increased rectal pressure. Rectal distension led to an increase in both the frequency and amplitude of PP and AP. Rectal myotomy below the 3rd electrode resulted in PP and AP disappearing distal but not proximal to the cut, excluding the 1st and 2nd electrodes, which did not show activity. The results suggest that PP start at the 3rd electrode, which corresponds anatomically to the rectosigmoid junction (RSJ). AP cause contractile activity along the rectum. It seems that the RSJ is the site of a pacemaker triggering the PP that pace the AP which initiate the rectal contractile activity. PMID- 8005172 TI - Pentoxifylline reduces skeletal muscle necrosis after acute hindlimb ischemia in rats. AB - Complete ischemia in the left hindlimb was maintained for 3.5 h in 16 rats randomized into two equal groups. One group served as control, the other was treated with pentoxifylline before, during and after the ischemic period. The animals were killed 72 h later, and the anterior tibial muscles were prepared for histological investigation. The most severely damaged muscles had a central core with complete necrosis of all muscle fibers, disintegrated capillaries and no macrophage infiltration. This zone, which was called the area of no resorption, was surrounded by an area of incomplete necrosis with partly resorbed muscle fibers, intact capillaries and marked macrophage infiltration. The muscles were completely intact only in a narrow subfascial zone. The total areas of necrosis and the areas of no resorption were measured as percent of the cross-sectional area of each muscle. There was extensive necrosis in both groups. The infarcted area was 93% in the control group and 89% in the treated group (NS). The corresponding areas of no resorption were 23 and 6% (p = 0.01). The study indicates that pentoxifylline has some protective effect on ischemic muscle damage. However, this effect is marginal compared to moderate hypothermic treatment. PMID- 8005173 TI - Postischemic hemodynamic changes after piroximone administration in isolated rabbit heart. AB - In an experimental study on 22 adult Elco rabbits, hemodynamic parameters were investigated using a working heart model. The study group (10 rabbit hearts) received 1 mg/kg i.v. of the phosphodiesterase inhibitor piroximone 15 min before thoracotomy. 12 untreated rabbit hearts served as a control group. Hemodynamic parameters were measured before and after 60 min of hypothermic ischemia. The pre ischemic period showed no significant differences between the two groups, except the higher levels of coronary flow in the piroximone group. The postischemic period showed significant increases in heart rate, coronary flow, aortic flow and cardiac output in the piroximone group in comparison to the control group. These results indicate as a main effect the positive influence of piroximone on coronary flow, given as a single shot 15 min preoperatively. This study provides evidence of the vasodilative properties on the coronary arteries beside the documented effects on the periphery. Therefore, piroximone represents an alternative tool in weaning from the cardiopulmonary bypass. PMID- 8005175 TI - Peripheral blood immune responses to surgically induced lung tissue injury. AB - Surgically induced lung tissue trauma reveals an immune response in peripheral blood, the degree of which could depend on extent and severity of the organ trauma and the presence of lung malignancies. The study included 34 patients who underwent elective thoracic surgery because of benign and malignant lung tissue diseases. Flow-cytometric phenotyping of lymphocyte subsets shows a clear shift to reduced immunocompetent cells after lung tissue injury. Patients with lung tumors reveal a postoperative activation of the macrophage system as indicated by increased plasma levels of neopterin. Increased levels of soluble interleukin-2 receptor in the plasma of these patients may be the result of cellular shedding of the receptor. Lung tissue trauma is also followed by reduced immunoglobulin levels which are most pronounced in the presence of lung malignancies. These results suggest that lung tissue injury leads to postoperative immunosuppression especially in tumor patients. PMID- 8005174 TI - Hepatic hemodynamics and oxygen metabolism during hepatic artery occlusion and reperfusion: effects of dobutamine and inhalation of 100% oxygen. AB - Hepatic hemodynamics, oxygen metabolism, and lactate metabolism during hepatic artery occlusion and reperfusion with and without supplemental oxygen and dobutamine (DOB) were studied in dogs. After a 60-min occlusion, hepatic arterial blood flow recovered about 80% of the preocclusion values after 10 min of reperfusion. However, portal vein blood flow gradually decreased during both occlusion and reperfusion. The partial pressure of oxygen in the portal vein blood (PPVO2) did not change significantly during the experiment. Accordingly, hepatic oxygen (HO2) delivery and consumption (HVO2) decreased markedly during occlusion and did not recover completely after 60 min of reperfusion. Although inhalation of 100% oxygen did not affect hepatic hemodynamics, it markedly increased PPVO2. DOB did not effectively increase PPVO2 though it increased portal vein flow (PVF). Both inhalation of 100% oxygen and DOB infusion enhanced HO2 delivery and HVO2 during hepatic artery occlusion and reperfusion. The hepatic lactate uptake was limited in the control group, however, it was improved by 100% oxygen and, especially, DOB both during occlusion and reperfusion. These data support the conclusion that inhalation of 100% oxygen and DOB administration effectively support hepatic function during hepatic artery occlusion. PMID- 8005176 TI - Utility of an excluded and everted segment of small intestine placed under the skin of the abdominal wall as an adrenal transplant site in rats. AB - The feasibility of excluded and everted small intestine segments as reservoirs for adrenal tissue transplantation was compared between biadrenalectomized adult rats with isogenic transplants of adrenal quarters or allogenic transplants of neonatal adrenal glands. Small clusters of adrenocortical cells, located between the adipocytes and the mesenteric vessels of the segments' lumen, were observed following isogenic transplantation. Several large regenerated adrenocortical nodules, surrounded by a connective capsule, were present in each of the rats transplanted with neonatal adrenal glands. Medullary tissue did not regenerate. It was concluded that the excluded and everted segments of small intestine were optimal sites for adrenal tissue transplantation and that the regeneration process of the adrenocortical tissue takes place more quickly after the transplantation of neonatal adrenal glands than after the transplantation of adrenal quarters. PMID- 8005177 TI - The effect of 5-fluorouracil on wound healing and collagen synthesis in left colon anastomoses. An experimental study in the rat. AB - In an experimental study resembling clinical use of adjuvant 5-fluorouracil (5 FU) treatment of colorectal carcinoma 86 male Wistar rats were operated with a standardized left colon resection and anastomosis with interrupted sutures. Treatment was given as daily intraperitoneal (i.p.) injections. The animals were randomized to one of two groups: (A) 5-FU (20 mg/kg) i.p., and (B) NaCl i.p. from the day of operation to sacrifice. Anastomotic complications were registered. In experiment 1 animals were randomized within treatment groups to be tested for anastomotic breaking strength with or without sutures in place when sacrificed 7 days postoperatively. In experiment 2 collagen synthesis was studied by an in vivo incorporation and hydroxylation of 3H-proline in the anastomotic segment during 24 h prior to sacrifice. The animals were sacrificed in groups on the third or seventh postoperative day. A higher number of anastomotic complications was registered when 5-FU was given. The anastomotic breaking strength was only 40% of controls both when tested with and without sutures. A reduced radioactivity of 3H-hydroxyproline in the anastomotic segment after 7 days of 5 FU treatment was found implying a reduction in collagen synthesis. In our model colonic healing was impaired after i.p. 5-FU treatment and this could be attributed to a reduced collagen synthesis in the wound gap as well as in the adjacent tissue responsible for the suture-holding capacity. PMID- 8005178 TI - Morphology following proctocolectomy in dogs: effect of introduction of a 'neocolon' using an interposed jejunal segment. AB - Intestinal mucosal morphology was studied in dogs given a new reconstruction procedure following proctocolectomy in which a jejunal segment was interposed between the terminal ileum and the anus to function as a 'neocolon'. Chronic inflammatory cell infiltration, villous atrophy, and fibrosis of the lamina propria were sought in three different intestinal sites and assigned a severity score. Twenty-four weeks after proctocolectomy, villous atrophy and fibrosis of the lamina propria were noted both in the interposed jejunum (neocolon) (p < 0.05, p < 0.01, respectively) and the terminal ileum (p < 0.05, p < 0.05, respectively). Similar changes were also observed in the proximal jejunum, but a significant difference compared to the preoperative time was not seen. Fibrosis of the lamina propria in the interposed jejunum tended to be more advanced than that in the other two sites. A statistical difference in severity was obtained between the interposed jejunum and the proximal jejunum (p < 0.05). Chronic inflammatory cell infiltration was similar in all sites examined. No obvious evidence of acute inflammation was found at any site examined. These data suggest that chronic morphologic changes inevitably occur at any site in the remaining intestine after proctocolectomy and that an interposed jejunal segment is most severely affected. The new interposition procedure may be effective in reducing the morphologic changes in the terminal ileum because of its proximal displacement. PMID- 8005179 TI - Ascorbate reduces gastric bleeding after hemorrhagic shock and retransfusion in rats. AB - The rat gastric mucosa, superfused with 0.1 N HCl, was investigated following 15 min of hemorrhagic shock and 30 min of retransfusion after pretreatment with ascorbate (1 mg/100 g b.w. or 5 mg/100 g b.w.). The size of the ischemic areas and the amount of mucosal bleeding using 51Cr labeling of red blood cells were assessed. Ischemic areas developed during shock. Following retransfusion, bleedings occurred at the border zones between ischemic and surrounding circulated areas. Ascorbate in both doses protected the gastric mucosa by reducing the amount of bleeding following 30 min of retransfusion as well as by reducing the area of ischemia 5 min after retransfusion. PMID- 8005180 TI - Quantitative assay of (1-3)-beta-D-glucan in culture media of Candida albicans using the G-test. AB - The diagnosis of invasive candidiasis is often difficult. The limulus test, which has been used for the assay of endotoxin in blood, was also found to react with (1-3)-beta-D-glucan, a component of the fungal cell wall. The factor in the limulus test that is activated by glucan, but not by endotoxin, is called factor G. The G-test utilizes the activation pathway starting with factor G, and sensitivity reacts with trace amounts of glucan. In this study, we investigated in vitro proliferation of Candida albicans and changes in the glucan concentration of RPMI-1640 media in the presence and absence of neutrophils and antifungal agents, as a pilot evaluation to possible clinical applications of the G-test. The proliferation of C. albicans and the glucan level measured in the culture media showed parallel changes. The glucan level in the culture media also increased when C. albicans was phagocytosed and digested by neutrophils, but not with administration of amphotericin B. The G-test closely reflected quantitative changes of C. albicans in vitro, and should be considered for future clinical studies in the diagnosis and evaluation of therapeutics in invasive candidiasis. PMID- 8005181 TI - Effect of longterm cetirizine treatment on the cutaneous hypersensitivity reaction in patients with grass pollen allergy. AB - In short-term studies cetirizine effectively reduces the early and late phases of the cutaneous hypersensitivity reaction. The aim of this study was to determine its long-term effects on both the vascular and cellular components of the reaction. The skin blister technique was used to collect inflammatory cells after intradermal administration of grass pollen antigen to 10 atopic volunteers. They were treated for 3 months with 10 mg cetirizine twice daily. Tests were done at baseline, before, and 7, 30 and 90 days after initiation of treatment. Blister fluid containing cells was collected on microscope slides at 6 and 24 hours. The area of induration was measured at 0.25, 1, 6, 10 and 24 h. Cetirizine significantly reduced the peripheral blood eosinophil count at 30 and 90 days (75% and 40% reduction respectively); there was no significant change after only one week's therapy. Eosinophil recruitment to and activation in the area of antigen administration were already maximally reduced after 7 days, namely a reduction of 54, 52 and 59% at 10 h, and of 55, 68 and 66% at 24 h, respectively, at 7, 30 and 90 days. The area of induration was significantly reduced after one week of therapy. There was a general tendency towards an increase in the reduction at 30 and 90 days, which reached significance only at the 24 h observation; there was a 24, 51 and 48% reduction from baseline at, respectively, 7, 30 and 90 days. The data clearly show a progressive reduction of induration as well as of cellular events over time.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8005182 TI - Central effects of repeated administration of atenolol and captopril in healthy volunteers. AB - The central effects of atenolol (50 mg tds) and captopril (50 mg tds) ingested for a period of seven days were studied in ten healthy volunteers. A placebo and two active control drugs, methyldopa (250 mg tds) and oxazepam (10 mg), were included in the design. Oxazepam was ingested on the seventh day only, with a placebo being taken on the preceding six days. On the seventh day, central effects of the drugs were tested at 10.00-11.00 h (session 1), immediately before the subjects' last dose of each drug and at 2.5-3.5 h after the final dose of each drug (1330-1430 h, session 2). Performance was assessed using digit symbol substitution, continuous attention, letter cancellation, choice reaction time, finger tapping, immediate and short-term memory, critical flicker fusion and two flash fusion. Subjects assessed their mood and well-being on a series of 12 visual analogue scales. Recordings of the EEG and body sway were carried out. Neither atenolol nor captopril altered performance at any of the skills tested. There were no effects on subjectively assessed alertness or mood with captopril, while atenolol significantly increased wakefulness in session 2 and when the two sessions were meaned. Similarly, captopril did not modify body sway, while with atenolol there was a significant decrease in activity in the frequency range 1.0 2.75 Hz from session 1 to session 2.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8005183 TI - Influence of input rates on (+/-)-isradipine haemodynamics and concentration effect relationship in healthy volunteers. AB - Since the magnitude of the response to a drug may depend upon the drug input rate, the concentration-effect relationship of the new dihydropyridine (+/-) isradipine was investigated using different administration modalities. Ten normotensive healthy volunteers were given, double-blind and in a crossover fashion, isradipine as a 1 mg iv infusion, 5 mg oral solution, 5 mg standard tablet, 10 mg slow release formulation, and a placebo. Blood pressure, heart rate, and plasma isradipine concentrations were recorded for 24 h. The maximal fall in diastolic blood pressure was similar after the infusion (-11.40 mmHg), the oral solution (-15.20 mmHg), and the standard tablet (-12.50 mmHg). In healthy volunteers the slow release form had no significant effect on blood pressure. The concentration-effect plots showed an increasing slope in the order infusion, solution, and table, and anticlockwise hysteresis. This was partly due to marked heart rate counter-regulation, the corresponding mean maximal heart rate increases being 24, 19, and 17 beats.min-1. The pronounced counter regulation of the heart rate implies that a slow isradipine input rate would be more effective in decreasing blood pressure. PMID- 8005184 TI - Sodium naproxen: concentration and effect on inflammatory response mediators in human rheumatoid synovial fluid. AB - Twelve patients suffering from rheumatoid arthritis and having swollen knees were treated with 1.1 g/day of sodium naproxen administered in one dose, daily for 5 days. The 72-h wash-out period was verified by the absence of any nonsteroidal anti-inflammatory drug using a HPLC screening. Blood and synovial fluid samples were drawn just before treatment and 24 h after the last dose. Eicosanoids (PGE2, 6-keto-PGF1 alpha, TXB2, LTB4, LTC4) in synovial fluid were determined by immunoenzymatic assays. In plasma and synovial fluid, hyaluronic acid was assayed by radiometric assay and sodium naproxen by HPLC. Free drug was determined by equilibrium dialysis. Statistical analysis used nonparametric tests. Pain relief (evaluated on a visual scale), morning stiffness, and scores on the Lee and Ritchie indices all decreased significantly, as did PGE2 and LTB4 concentrations. The decrease in 6-keto-PGF1 alpha and TXB2 was not significant. No significant change was found for LTC4 and hyaluronic acid. Total concentrations of sodium naproxen were equivalent in plasma (16.1 micrograms.ml-1) and synovial fluid (18.9 micrograms.ml-1). Free fractions were significantly higher in synovial fluid (0.14%) than in plasma (0.11%), as shown by binding of the drug to human serum albumin, at various protein concentrations. Interestingly, the clinical efficacy, as shown by decreases in morning stiffness and in the Lee index score, correlated with the free concentration of naproxen in synovial fluid. PMID- 8005185 TI - A pharmacokinetic and pharmacodynamic evaluation of the combined administration of alprazolam and fluvoxamine. AB - We have assessed the pharmacokinetic and pharmacodynamic interaction between fluvoxamine, a serotonin reuptake inhibitor, and alprazolam, a triazolobenzo diazepine. Healthy men took fluvoxamine maleate daily for 10 days (50 mg on days 1-3, 100 mg on days 4-10) (n = 20), 1 mg of alprazolam four times daily for four days (days 7-10 of the study period) (n = 20), or a combination of the two (n = 20), according to a parallel study design. Alprazolam and fluvoxamine concentrations were measured in serial plasma samples by HPLC and gas chromatography respectively, and psychomotor performance and memory were assessed on days 1, 7, and 10. Fluvoxamine increased plasma alprazolam concentrations by 100%. The mean apparent half-life of alprazolam was increased from 20 h to 34 h after fluvoxamine co-administration. The increased plasma concentrations of alprazolam resulted in significantly greater reductions in psychomotor performance evident on day 10. Mean fluvoxamine plasma concentrations were about 25% lower in those who took the combination than in those who took only fluvoxamine; this was more likely due to heterogeneity between the treatment groups than to an effect of alprazolam. The dosage of alprazolam should be reduced during co-administration with fluvoxamine. PMID- 8005187 TI - Kinetic interaction between theophylline and a newly developed anti-allergic drug, pemirolast potassium. AB - The effect of a newly developed anti-allergic drug, pemirolast potassium (TBX), on the pharmacokinetics and metabolism of theophylline was investigated under steady-state conditions in seven healthy male volunteers. A sustained-release theophylline formulation (100 mg twice daily at 12 h intervals) was given as monotherapy and coadministered with TBX (10 mg twice daily at 12 h). Plasma concentration-time curves and the urinary excretion of theophylline and its major metabolites after administration of theophylline alone and after coadministration with TBX were compared. No significant adverse effects from this study were observed. There were no significant differences in the total body clearance, renal clearance and maximum concentration of theophylline between the two treatments, although coadministration of TBX significantly delayed the time to reach maximum concentration of theophylline. In the case of urinary excretion, no significant changes in the fraction of urinary excretion of theophylline and its metabolites were observed. These results indicate that TBX has little or no effect on the pharmacokinetics and metabolism of theophylline and suggest that TBX is safe for asthma patients receiving theophylline therapy for treatment of chronic obstructive airway diseases. PMID- 8005186 TI - Human liver budesonide sulphotransferase is inhibited by testosterone and correlates with by testosterone sulphotransferase. AB - Budesonide, a corticosteroid used in the treatment of asthma and allergic reactions, is almost entirely cleared by metabolism in man. We describe the sulphation of budesonide in human liver and lung and provide evidences that the sulphation of budesonide is catalysed by testosterone sulphotransferase. A rapid and reproducible radiometric assay for budesonide sulphotransferase is described. Liver specimens were obtained from 35 men and 65 women and lung specimens from 2 women and 17 men. The average hepatic budesonide sulphation rate was significantly higher in men (41.1 pmol.min-1.ml-1) than women (28.2 pmol.min-1.mg 1). In the lung, the mean budesonide sulphation rate was 5.0 pmol.min-1.mg-1. Testosterone strongly inhibited the hepatic sulphation of budesonide, whereas p nitrophenol and dopamine were poor inhibitors; the IC50 was 7.0 uM (testosterone), 320 uM (p-nitrophenol) and 510 uM (dopamine). The hepatic rates of testosterone, p-nitrophenol and dopamine sulphation were measured in the same samples assayed for budesonide sulphotransferase. There was a correlation between the hepatic rates of budesonide and testosterone sulphation (P < 0.001; r = 0.810). The activity of testosterone sulphotransferase was significantly greater in men than women (22.0 vs. 17.2 pmol.min-1.mg-1), whereas those of dopamine and p-nitrophenol sulphotransferase were not sex dependent.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8005188 TI - Histamine-induced airway mucosal exudation of bulk plasma and plasma-derived mediators is not inhibited by intravenous bronchodilators. AB - Experimental data suggest the possibility that common bronchodilators, such as the xanthines and beta 2-adrenoceptor agonists, may produce microvascular anti permeability effects in the subepithelial microcirculation of the airways. In this study, we have examined the effect of bronchodilators given intravenously on exudation of different-sized plasma proteins (albumin and fibrinogen) and the generation of plasma-derived peptides (bradykinins) in human nasal airways challenged with histamine. In a double-blind, crossover, placebo-controlled and randomised trial, 12 normal volunteers were given i.v.infusions of terbutaline sulphate, theophylline and enprofylline to produce therapeutic drug levels. The effect of topical nasal provocation with histamine was closely followed by frequently nasal lavage with saline. The lavage fluid levels of albumin, fibrinogen and bradykinins increased significantly after each histamine provocation. The ratio of albumin-to-fibrinogen in plasma and the lavage fluid was 24 and 56, respectively, indicating that topical histamine provocation induced a largely non-sieved flux of macromolecules across the endothelial epithelial barriers. The systemically administered drugs did not affect the nasal symptoms (sneezing, secretion and blockage), nor did they significantly reduce the levels of plasma proteins and plasma-derived mediators in the nasal lavage fluids. The present data suggest that systemic xanthines and beta 2-adrenoceptor agonists, at clinically employed plasma levels, may not affect the microvascular (and epithelial) exudative permeability and the bradykinin forming capacity of human airways. PMID- 8005189 TI - Nonlinear kinetics of nortriptyline in relation to nortriptyline clearance as observed during therapeutic drug monitoring. AB - From routine therapeutic drug monitoring data, samples from 105 patients with two analyses of nortriptyline at different daily doses were collected. The ratio between concentration and daily dose, which is the reciprocal of the apparent clearance, was compared intra-individually to study the occurrence of dose dependent kinetics. Subjects with a low or intermediate ratio at the low dose had a higher mean ratio at the high dose, indicating a nonlinear relationship between dose and concentration. The magnitude of the difference was inversely correlated to the ratio at the low dose. No major difference was seen in the ca. 10% of the patients that exhibited the highest ratio at the low dose. This fraction corresponds to the frequency of poor metabolizers of debrisoquine in the population. The metabolism of nortriptyline has been shown to be partly dependent on the debrisoquine hydroxylase CYP2D6. We conclude that dose-dependent kinetics of nortriptyline occurs in subjects with a high or intermediate capacity to eliminate the drug, in accord with debrisoquine hydroxylase being a high affinity, low-capacity pathway in the elimination of nortriptyline. PMID- 8005191 TI - Weighted serum pools in comparison to the trapezoidal rule for estimating AUCs for ethinyl estradiol. The relationship of the variance of the determination to the interindividual variance. AB - The concept of a weighted pool for estimating the area under the curve (AUC) is presented and set in relationship to the trapezoidal rule. An example from a pharmacokinetic study on ethinyl estradiol is used to demonstrate the use of variance component analysis for relating the intraindividual variance of the AUC, trapezoidal rule and weighted pool to the variance of the determination process. Depending on the sampling times, the theoretical variance of the weighted pool is greater than the theoretical variance of the trapezoidal rule. In the example presented, it was shown that this difference is of no importance in relation to the interindividual variance of the AUC, which dominates the total variance. In the example study, routine quality control samples were also determined in each assay, which allowed independent confirmation of the discussed results on the intraindividual variance of the AUCs. PMID- 8005190 TI - Topical formulations of fluocinolone acetonide. Are creams, gels and ointments bioequivalent and does dilution affect activity? AB - The study was done in healthy volunteers to investigate the vasoconstrictor activity of three commercially available formulations of fluocinolone acetonide (Synalar gel, cream and ointment) and to determine whether they were bioequivalent. The influence of dilution of the cream formulation on activity was also examined. Twenty mg of each topical formulation was applied, followed by occlusion for 6 h, and the potency was evaluated by measuring the vasoconstrictor effect using tristimulus colour analysis. The cream formulation was more potent than the ointment, with the gel having intermediate strength. Dilution did not significantly reduce activity. While choice of an appropriate topical corticosteroid formulation largely depends on the nature of the lesions, this study has shown that different formulations of nominally the same concentration have different potencies; dilution up to 1 in 10 produced no significant reduction in potency. The potency classification in the British National Formulary for formulations of Synalar may need revision. PMID- 8005192 TI - Plasma levels of oxybutynine chloride in children. AB - Anticholinergic adverse-effects in children treated with conventional doses of oxybutynine led us to measure plasma oxybutynine levels in children. 18 children, aged 5 to 13 y, who required treatment with oxybutynine chloride for daytime incontinence were studied. Plasma concentrations were measured on the fifth day of a course of treatment in which the dose was adapted to the child's body weight; the dose was given twice daily at 12-hour intervals. In 10 children aged between 5 and 8 y, the mean dose was 0.1 mg.kg-1. In 8 children aged between 10 and 13 years, the mean dose was 0.15 mg.kg-1. The highest concentration was usually found between 1 and 2 h after administration. The subsequent fall in concentration was rapid and after 6 h oxybutynine was no longer measurable in 14 of the children. The concentrations found were not different from those seen in adults given equivalent doses. The results show that plasma concentrations in children were not very different from those observed in adults if the dose were adapted to the body weight of the children. No special differences in paediatric use were revealed that might explain the particular adverse-effects. The results of the study argue against the dosage regimen proposed before these adverse events were detected. They strongly favour a dose adapted to the body weight of the child, with a 12-hour interval between doses. PMID- 8005194 TI - Ivermectin levels in human breast milk. PMID- 8005193 TI - Concentration of meropenem in serum and in bronchial secretions in patients undergoing fibreoptic bronchoscopy. AB - The objective of the study was to evaluate the ability of meropenem to reach the bronchial lumen. 24 patients undergoing fibreoptic bronchoscopy for exploratory purposes were given a single dose of meropenem 1 g as an (i.v., infusion over 30 min. Plasma (P) sampling times were: 0, 0.5, 1, 2 and 3 h. Bronchial secretions (BS) were collected by fibreoptic bronchoscopy at the same sampling times (except for 0 and 0.5 h) in three groups of 8 patients. Meropenem was measured by bioassay using E. coli ATCC 39118 as the test-organism. The results showed that meropenem had reached a high plasma concentration at the first sampling time (59.8 mg.l-1) and then the plasma level decreased rapidly to 10.6 mg.l-1 and 2.7 mg.l-1 at 2 and 3 h respectively. The highest concentration achieved in bronchial secretion was 0.53 mg.l-1 in the third hour, ie 20% of the serum level. The data indicate significant penetration of meropenem into bronchial secretions and achievement of a local level sufficiently high to eradicate most respiratory pathogens. PMID- 8005196 TI - Equal efficacy of both cimetidine formulations for the healing of gastric ulcer. PMID- 8005195 TI - The saluretic effect of the thiazide diuretic bemetizide in relation to the glomerular filtration rate. AB - The effect of the thiazide diuretic, bemetizide, on the excretion of Na+, K+, Cl , Ca2+, and Mg2+ in relation to the glomerular filtration rate (GFR) was studied in 17 subjects whose creatinine clearances ranged from 133 to 5 ml.min-1. After a 2-day fluid and salt balanced control period, 25 mg bemetizide given orally induced natriuresis and kaliuresis which lasted for 24 h and were proportional to the GFR of the patients. The ratio of bemetizide-induced K+/Na+ excretion was always 0.17 irrespective of individual GFR. In renal failure, bemetizide increased the fractional Na+ excretion from 3% to about 10%. Kaliuresis was associated with magnesiuria, whereas bemetizide-induced calciuresis was insignificant. The thiazide reversibly lowered GFR in all subjects. PMID- 8005197 TI - Craniofacial morphology in patients with multiple congenitally missing permanent teeth. AB - The purpose of this study was to examine the association between the number of congenitally missing permanent teeth, excluding third molars, and the craniofacial morphology. The sample comprised 118 children with five or more congenitally missing teeth. Twenty-seven reference points were digitized from lateral cephalometric radiographs and 13 angular measurements of craniofacial morphology were calculated. After an initial analysis, the sample was divided into two subsamples, one with 5-12 missing teeth and the other with 13-21 missing teeth. Within each subsample there was no significant association between number of missing teeth and the angular variables, but a comparison between the two subsamples showed significantly smaller mandibular plane inclination (NSL/ML, NL/ML) and gonial angle (RL/ML), and a more prognathic mandible (s-n-pg) in the subsample with more than 12 teeth missing. It is suggested that the difference in morphology could be due to a reduced vertical development of the lower face, caused by a reduced occlusal support in the subsample with more than 12 congenitally missing teeth. PMID- 8005198 TI - Validity of cephalometric landmarks. An experimental study on human skulls. AB - Cephalometric landmark validity (the difference between the estimated landmark and the true landmark) has surprisingly not previously been comprehensively evaluated, and no previous study has examined the validity of cephalometric angles and distances. The aim of this study was to investigate the validity of 15 commonly used skeletal and dental cephalometric landmarks, and the subsequent effects on 17 angles and distances. Small steel balls were glued on to 30 Chinese dry skulls to represent the true anatomical landmarks. The skulls were mounted in a purpose-designed skull holder and two cephalograms recorded of each skull, one with and one without the steel balls on the landmarks. Validity was expressed as the difference in the measurements between the assessments made with and without the steel ball markers. Measurements were made relative to X and Y co-ordinates which were constructed from reference points (steel balls) glued intracranially to the skulls. Seven out of the 10 skeletal landmarks and all five dental landmarks, were found to be non-valid along the X or the Y axes (P < 0.05). The standard deviations of the validity errors were large, being 1.0-2.5 mm, along at least one axis, for eight of the skeletal landmarks and three of the dental landmarks. Four of the cephalometric angles (SNA, SN/MnP, MxP/MnP, and LI/MnP) and three of the distances (N-Me, MxP-Me, and lower incisor edge to APg) were also found to be invalid (P < 0.05). The validity errors were greater for angles involving dental landmarks and for angles dependent on four landmarks compared to those dependent on three. The standard deviations of the validity errors for the skeletal angles ranged from 0.9 to 1.8 degrees, except for ANB (0.4 degrees), and for the dental angles from 3.2 to 5.8 degrees. PMID- 8005199 TI - The alignment of permanent mandibular incisors in children. A longitudinal prospective study. AB - The aim was to study the alignment of mandibular incisors before and after eruption of the canines, and if possible to find a method of predicting space deficiency. Fifty-three children with normal occlusion or untreated mild post normal occlusion had plaster models taken at 7, 9, 10, and 13 years of age. An estimation of the space situation for the mandibular incisors was made using a scale with five levels. Measurements of intercanine distance, width of each incisor and space available between the canines were made. Greater crowding was seen before the eruption of permanent canines than after the start of eruption. Estimation of space showed significant correlations to measurements of inter canine distance. Children with an excess of incisal space had a wider mandibular inter-canine distance compared with those with a deficiency of space. Among 7-, 9 , and 10-year-old children an inter-canine distance of less than 26 mm was associated with crowding. A distance of 28 mm or more was estimated as no risk for crowding. PMID- 8005200 TI - Effects of TGF-beta 2 on mineral resorption in cultured embryonic mouse long bones; 45Ca release and osteoclast differentiation and migration. AB - To study the effects of transforming growth factor beta 2 (TGF-beta 2) on bone resorption, cultures of 17-day-old foetal mouse metatarsal long bones were used. The long bone rudiments were cultured for 5 days in medium supplemented with 10% rat serum. The effects of TGF-beta 2 were studied at concentrations of 1, 4, and 10 ng/ml. At all concentrations TGF-beta 2 caused a significant reduction in osteoclastic resorption measured as release of 45Ca from prelabelled bones. The same long bones were subsequently used for histological evaluations. Pre osteoclasts and osteoclasts were identified as tartrate resistant acid phosphatase (TRAP) positive cells in the mineralized diaphysis, the periosteum around the diaphysis, and the perichondrium around the cartilaginous ends. The distribution of TRAP-positive cells over the three compartments showed that TGF beta 2 inhibited the migration of TRAP-positive cells from the periosteum into the mineralized diaphysis in a dose dependent manner. In addition, TGF-beta 2 had a biphasic effect on TRAP cell differentiation, as 1 ng/ml increased, but 4 ng/ml and higher decreased TRAP cell numbers. We conclude that TGF-beta 2 is a potent regulator of osteoclastic bone resorption, by modulating both osteoclast migration and osteoclast differentiation. PMID- 8005201 TI - Growth of the nasal septum in the Snell strain of hypopituitary dwarf mouse. AB - The literature relating to experimental investigation of growth of the nasal septum has been reviewed in detail. A total of 156 skulls from the Snell hypopituitary mouse, six controls and six dwarfs at each age group were radiographed in lateral view to enable measurement of the different components of the nasal septum. By 80 days of age, the snout of the nasal septum in the Snell strain of mice was 56 per cent the size of the snout in normal mice (n = 12, t = 8.07, P = 0.0005). It is concluded that the Snell strain of mouse is an example of a specific genetic defect causing severe growth retardation of cartilaginous tissues, particularly the nasal complex. PMID- 8005202 TI - Class II: a comparison of activator and activator headgear combination appliances. AB - The purpose of this study was to evaluate skeletal and dental effects of activator and activator high-pull headgear combination appliances on growing patients with Class II, division 1 malocclusion. The material consisted of pre- and post-treatment cephalograms of 17 boys and 20 girls. Seventeen patients (eight male and nine female) were treated with an activator, the remaining 20 (9 male and 11 female) were treated with an activator high-pull headgear combination (AHGC) appliance. Changes due to treatment were compared with a group of 19 (nine male and ten female) untreated children. ANB angle was significantly reduced and mandibular growth development was favourable in both treatment groups. The AHGC appliance was more effective in the reduction of the maxillary prognathism. An increase of the anterior facial height and clockwise rotation of the occlusal plane was observed in the patients treated with activator appliance. The cant of the mandibular plane remained stable during both treatment periods. On the other hand, the forward displacement of the upper first molars was reduced significantly and the axial inclination of the lower incisors was controlled much better with the AHGC appliance. PMID- 8005204 TI - Atlas morphology in relation to craniofacial morphology and head posture. AB - The associations between dimensions of the first cervical vertebra, atlas, and a representative set of craniofacial and postural variables were studied on cephalometric radiographs of a sample of 103 adult males aged 22-30 years, recorded in the natural head position (mirror position). Atlas morphology was expressed by nine variables, linear and angular craniofacial dimensions by 27 variables, and head and cervical posture by seven variables. A pattern of low but significant correlations was found. Although the correlations were low, the study confirmed that the dimensions of the atlas vertebra reflect associations between cranio-cervical posture and craniofacial morphology. Negative correlations were found between the height of the posterior arch of atlas and the inclination of the mandible and the maxilla to the anterior cranial base. Low positive correlations between the height of the anterior arch and vertical facial dimensions reflect the general co-ordination of the vertical growth of the face and the cervical column. Moreover, the pattern of correlations between the atlanto-cranial angle and facial morphology suggests that in changes of the cranio-cervical angle, atlas follows the cervical column. PMID- 8005203 TI - Osseointegrated implants in adolescents. An alternative in replacing missing teeth? AB - In 15 adolescents (13 years 2 months-19 years 4 months) in the late dental stage, Branemark implants (n = 27) were chosen to replace missing teeth due to congenital absence or trauma. The patients were followed for at least 3 years, at yearly intervals, biometrically and radiographically. No fixture losses occurred. Only minor loss of bone support at the fixtures was observed, while adjacent tooth surfaces showed some loss in some cases. Infra-occlusion of the implant restorations was noticed in patients with residual craniofacial growth. Thus, the dental and skeletal maturation, and not the chronological age of the patient, must be taken into consideration to avoid infra-occlusion of the fixture crown. Furthermore, it is important to gain enough space for the fixture in the mesio distal direction, to avoid the risk of marginal bone loss at teeth that are adjacent to it. PMID- 8005205 TI - The antiandrogen cyproterone acetate: discovery, chemistry, basic pharmacology, clinical use and tool in basic research. PMID- 8005206 TI - Pituitary function tests: comparison of ACTH and 11-deoxy-cortisol responses in the metyrapone test and with the insulin hypoglycemia test. AB - PURPOSE: To compare the sensitivity of ACTH and 11-deoxy-cortisol (comp. S) responses in the short metyrapone test and the latter with the insulin hypoglycemia test. METHODS: Retrospective evaluation of 115 short metyrapone tests and comparison of 18 pairs of metyrapone and insulin tests. 20 healthy controls and 95 patients with confirmed pituitary disease were studied. All hormones were measured by sensitive radioimmunoassays. RESULTS: In patients with pituitary disease not requiring hydrocortisone substitution (n = 70), the ACTH response in the metyrapone test was subnormal in 47 cases (< 33 pmol/L), the comp. S response (< 200 nmol/L) in 21 cases only. Comparison of the relationship between ACTH and comp. S with an ACTH-cortisol dose-response curve obtained in normal subjects shows that subnormal ACTH responses after metyrapone in the range between 13 and 33 pmol/L still generate normal comp. S responses. The results of the metyrapone test correlated significantly with those of the insulin test. CONCLUSIONS: Measuring plasma ACTH in the scope of the metyrapone test makes the test more sensitive to detect secondary adrenal insufficiency than with steroid measurements alone. Results of the metyrapone test correlate significantly with the cortisol response to insulin hypoglycemia. PMID- 8005207 TI - Time-resolved fluoroimmunoassay (TR-FIA) of gonadotropins. AB - Time-resolved fluoroimmunoassay (TR-FIA), which has recently been developed as a non-isotopic immunoassay, was intended for assay of gonadotropins (LH and FSH). Ovine LH or FSH was labeled with N1-(p-isothiocyanatobenzyl)-diethylenetriamine N1, N2, N3, N3-tetraacetic acid Eu-chelate (DTTA), and competitive binding assay was performed using a 96-weel titer plate previously coated with a second antibody, followed by measurement using time-resolved fluorometry. TR-FIA for standard ovine LH (NIDDK, LH-I-3) or FSH (NIDDK, FSH-I-1) had a sensitivity of about 25 pg/50 microliters sample. The assay system was applied to heterologous assay of porcine gonadotropins. Linearity was obtained by the dilution test using medium from primary culture of porcine anterior pituitary cells. Intra- and inter assay coefficients of variation of LH and FSH determination in 31 different porcine samples were satisfactorily low, between 3.5 and 8.1% (intra-assay) and between 1.7 and 13.1% (inter-assay). Correlation coefficients between radioimmunoassay and TR-FIA were calculated to be 0.945 for LH and 0.978 for FSH. Stimulation of LH and FSH release with GnRH was observed by TR-FIA. This non isotopic TR-FIA thus provides as good sensitivity, reproducibility and accuracy as conventional RIAs. PMID- 8005208 TI - Bone mineral density and calcium regulating hormones in patients with inflammatory bowel disease (Crohn's disease and ulcerative colitis). AB - Inflammatory bowel disease (Crohn's disease and ulcerative colitis) is associated with decreased bone mineral density and increased risk of osteoporosis. However, the pathogenesis of this bone loss is not yet fully understood. In the present study we measured lumbar bone mineral density (by dual photon absorptiometry), serum levels of parathyroid hormone (PTH) and vitamin D metabolites, and serum markers of bone turnover (alkaline phosphatase and osteocalcin) in 15 patients with Crohn's disease and in 4 patients with ulcerative colitis. The median duration of the disease was 4 years and the median lifetime steroid dose was 10g of prednisone. We compared our results to a control group of 19 normal persons, who were matched for age and sex to the patients. We found that lumbar bone density was reduced by 11% in patients compared with control persons (Z-score 0.6 +/- 0.6 versus -0.1 +/- 0.8; p < 0.05). In patients, the serum levels of PTH, 25-hydroxyvitamin D3, and calcitriol (1,25(OH)2D3) were significantly reduced compared with control persons. Serum alkaline phosphatase activity (AP) was significantly higher in the patients and was inversely related to lumbar bone density. Osteocalcin values were not different between patients and control persons. There was also no difference in serum levels of calcium between the two groups, whereas phosphorus levels were higher in patients. We conclude that malabsorption of calcium was not a primary cause of bone loss in our patients, because we did not find secondary hyperparathyroidism. Accordingly, we did not find a severe vitamin D deficiency, since 25-hydroxyvitamin D3 levels were within the normal range.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8005209 TI - Complete remission of metastasized adrenocortical carcinoma under o,p'-DDD. AB - The case of a 53 year old female patient with metastasized androgen producing adrenocortical carcinoma is presented. After initial adrenalectomy a local relapse had been treated by surgery and external irradiation. Solitary liver metastases had been resected repeatedly. Subsequently multiple liver metastases required systemic chemotherapy. Treatment with o,p'-DDD (initially 12 g/d, long term treatment 1.5-3 g/d) has resulted in a complete remission for nearly 4 years. Gastrointestinal side effects occurred initially but subsided with dose reduction of o,p'-DDD. PMID- 8005210 TI - An outbreak of Escherichia coli O157 associated with a children's paddling pool. AB - In May 1992, a small, circumscribed community outbreak of infection due to verotoxin-producing Escherichia coli O157 phage type 49 occurred in a semi-rural area of south-east Scotland. On the basis of stool cultures, six cases were identified, one of whom was asymptomatic. One child developed the haemolytic uraemic syndrome. Although the source of infection of the index case was not established nor could the extent of person-to-person spread be fully determined, the clinical, microbiological and epidemiological evidence available indicated that a children's paddling pool served as the focal point in the transmission of infection causing the outbreak. PMID- 8005211 TI - Sequence heterogeneity of the eae gene and detection of verotoxin-producing Escherichia coli using serotype-specific primers. AB - The distribution of the Escherichia coli attaching and effacing (eae) gene in strains of verotoxin-producing E. coli (VTEC) isolated from cattle and humans was studied. The majority of strains isolated from humans with bloody diarrhoea or HUS and cattle with severe diarrhoea were eae positive (82 and 83% respectively). In contrast, 59% of VTEC isolated from asymptomatic cattle were eae negative and of the remaining 41% that were eae positive, the majority were serotype O157. H7. The nucleotide sequence of the 3' end of the eae gene of enteropathogenic E. coli (EPEC) of serotype O55. H7 was found to be almost identical to that of serotype O157. H7. Specific primers are described which detect the eae sequences of VTEC serotypes O157. H7, O157. H-, and EPEC serotypes O55. H7 and O55. H-. The nucleotide sequence of the 3' end of the eae gene of serotype O111. H8 differed significantly from that of O157. H7. Primers were developed to specifically identify the eae sequences of VTEC serotypes O111. H- and O111. H8. We conclude that whereas the majority of VTEC associated with disease in cattle and humans possess the eae gene, the gene itself may not be necessary to produce haemorrhagic colitis and HUS. Sequence heterogeneity in the 3' end of eae alleles of VTEC permits specific identification of subsets of these organisms. PMID- 8005213 TI - Apramycin-resistant Escherichia coli isolated from pigs and a stockman. AB - Escherichia coli serotype O147:K89:K88a,c was found to be associated with outbreaks of diarrhoea in preweaner pigs of up to 4 weeks of age on a pig unit. Resistance to apramycin, gentamicin, netilmicin, tobramycin and other antibiotics was associated with conjugative plasmids of approximately 62 kb. The presence of a gene which encoded for the aminoglycoside acetyltransferase enzyme AAC(3)IV was confirmed by DNA hybridization. Samples collected during the following 12 months revealed widespread dissemination of these resistance plasmids in non serotypable, non-haemolytic E. coli throughout the farm. Apramycin-resistant E. coli were also isolated from a stockman and it appeared from plasmid profile analysis and antibiotic sensitivity testing that the human isolates carried the same plasmid as that carried by the porcine E. coli. Klebsiella pneumoniae, with a slightly smaller conjugative plasmid and similar resistance pattern, was isolated from the stockman's wife. PMID- 8005212 TI - An epidemic of cholera due to Vibrio cholerae O139 in Dhaka, Bangladesh: clinical and epidemiological features. AB - We describe the disease spectrum and socio-demographic and epidemiological features of an epidemic of cholera due to a new pathogen, Vibrio cholerae O139, in patients attending a very large hospital in the metropolitan city of Dhaka, Bangladesh. This hospital treats 70,000-90,000 patients a year with diarrhoeal diseases. A 4% systematic sample of 1854 patients attending from January to April 1993 were studied. Five hundred and two (27%) of the 1854 patients were culture positive for V. cholerae O139 and 63 (3%) were culture positive for V. cholerae O1 biotype El Tor. Patients with V. cholerae O139 were mainly adults with a short history of watery diarrhoea. Eight-three percent of patients had moderate to severe dehydration. All recovered except one 80-year-old man with compromised renal function who died. Seventy-eight percent of patients required initial intravenous rehydration followed by oral rehydration therapy with rice ORS; they also received tetracycline to reduce diarrhoea severity. Most patients were from urban slums with inadequate sanitation facilities and hygiene practices. The newly recognized V. cholerae O139 infection produced an epidemic of severe dehydrating diarrhoea indistinguishable from clinical cholera in a population which experiences two epidemic peaks of cholera in a year due to V. cholerae O1. Infection with the latter does not appear to confer any cross-protection from V. cholerae O139. The new pathogen suppressed, albeit temporarily, V. cholerae O1. Unlike other non-O1 serogroups of V. cholerae this new serogroup appears to have epidemic potential. PMID- 8005214 TI - Community-based study of the incidence of gastrointestinal diseases in The Netherlands. AB - The incidence of gastrointestinal diseases was studied in a community-based study in four regions of The Netherlands. Two grades of severity were distinguished--1: diarrhoea or vomiting and at least 2 additional symptoms within the period of 1 week, and 2: diarrhoea or vomiting and at least 2 additional symptoms occurring on the same day lasting at least 2 days within the period of 1 week. The incidence of gastrointestinal episodes was calculated to be 630 for grade 1 and 180 for grade 2 disease per 1000 person-years, after correction for age and sex. The incidence was higher for women than for men (relative risk 1.25) and lower for those in the 19-64-year-old age group when compared to those younger or older (relative risk 0.75 and 0.40, respectively). Independent of the degree of severity of the symptoms, about 20% of the patients had consulted a general practitioner, about half in person and half by telephone. It is concluded that community studies are essential to assess the real incidence of gastrointestinal diseases in the population. PMID- 8005215 TI - Epidemiology of Staphylococcus aureus in patients with cystic fibrosis. AB - Seven hundred and thirty-four isolates of Staphylococcus aureus, recovered from the sputum of 238 cystic fibrosis patients in six French hospitals, were characterized by esterase electrophoretic typing, capsular polysaccharide serotyping and phage typing and tested against 14 antibiotics for sensitivity. Thirty-four esterase electrophoretic types were found with a genotypic diversity coefficient of 0.91. Five hundred and forty-eight (78.7%) isolates produced capsular polysaccharide and 350 (50.3%) were type 8. Four hundred and sixty isolates (66.6%) were phage typable and 202 (28.2%) were lysed by group III bacteriophages. No esterase electrophoretic type, capsular type or phage type was specific to cystic fibrosis. Isolates belonged to a wide range of types, similar to strains acquired outside hospitals. Eighty-five patients had three or more consecutive isolates over at least 6 months. The ability of S. aureus to persist for long periods of time has been demonstrated in 73% of them. Methicillin resistance was encountered among 73 strains (9.8%) which were also multiresistant. Two hundred and eighty-nine (39.9%) strains were sensitive to all antibiotics tested except to penicillin. Pristinamycin and co-trimoxazole were the most effective antibiotics. These results could contribute to the elaboration of a rational approach to the prophylaxis and therapy of respiratory staphylococcal infections in cystic fibrosis patients. PMID- 8005216 TI - Clonal study of enterotoxin-B producing strains of Staphylococcus aureus. AB - Sixty-nine Staphylococcus aureus strains, 39 of which produced staphylococcal enterotoxin B (SEB+) and 14 of which were associated with toxic shock (TS+), were studied using the following markers: serotyping, phage typing, antibiotyping, ribotyping, zymotyping and pulsed-field electrophoresis typing. Analysis of the results showed that the enterotoxin B producing strains were derived from at least three clones: the first two consisted of methicillin-susceptible strains, while the third included the methicillin-resistant (MRSA) strains. TS+ strains of nongenital origin appeared to be distributed between the three clones, with no specific characters. PMID- 8005218 TI - Seroprevalence of leptospirosis in a rural flood prone district of Bangladesh. AB - Leptospirosis is a worldwide zoonotic disease. In the present investigation, a total of 89 human sera from a flood prone district of Bangladesh was screened by a one-point microscapsule agglutination test (MCAT). MCAT-positive and -doubtful sera were further tested by microscopic agglutination test (MAT) against 16 reference serovars of Leptospira interrogans, and the antibody titres determined. In MCAT, 34 sera were positive and 22 were doubtful. Among those positive and doubtful sera, 33 and 20, respectively were tested by MAT. Thirty-four out of 53 MCAT-screened samples were MAT-positive. The titres ranged from 20 to 1600 with antibodies to serovars copenhageni, australis, cynopteri and icterohaemorrhagiae being the most prevalent. Eleven MCAT-positive samples failed to react with any strains used by MAT, suggesting the presence of new or untested serovars. Among the MAT-positive samples, the presence of antibody against two or more serovars was more common than that of a single serovar. The present study suggests that rural people in Bangladesh are at high risk to leptospiral infection. PMID- 8005217 TI - Fatal nosocomial Legionnaires' disease: relevance of contamination of hospital water supply by temperature-dependent buoyancy-driven flow from spur pipes. AB - The investigation, epidemiology, and effectiveness of control procedures during an outbreak of Legionnaires' disease involving three immunosuppressed patients are described. The source of infection appeared to be a network of fire hydrant spurs connected directly to the incoming hospital mains water supply. Removal of these hydrants considerably reduced, but failed to eliminate, contamination of water storage facilities. As an emergency control procedure the incoming mains water was chlorinated continuously. Additional modifications to improve temperature regulation and reduce stagnation also failed to eliminate the legionellae. A perspex test-rig was constructed to model the pre-existing hospital water supply and storage system. This showed that through the hydraulic mechanism known as 'temperature buoyancy', contaminated water could be efficiently and quickly exchanged between a stagnant spur pipe and its mains supply. Contamination of hospital storage tanks from such sources has not previously been considered a risk factor for Legionnaires' disease. We recommend that hospital water storage tanks are supplied by a dedicated mains pipe without spurs. PMID- 8005220 TI - Subtyping of Mycobacterium avium complex (MAC) isolates by thin-layer chromatography--distribution of subtypes from patients with AIDS compared with clinically non-significant isolates. AB - Thin-layer chromatography (TLC) was compared with seroagglutination for subtyping of Mycobacterium avium complex (MAC) bacteria. Seventy-five significant MAC isolates from patients with AIDS were typed by both methods and 36 isolates, judged to be clinically non-significant, were examined by TLC only. Overall, 75% of isolates tested were typable by seroagglutination and 91% by TLC; the results correlated between the two except for minor discrepancies. Serovars 1, 8 and 21 and mixed serovars 1-21 and 1-8-21 were common among isolates from AIDS patients and together represented 83% of isolates compared with only 36% in the non significant group (odds ratio 8.4; 95% confidence interval 3.4-23.3). This difference remained significant after exclusion of serovar 41 (M. scrofulaceum), which was the commonest isolate (28%) in the non-significant group but was not isolated from patients with AIDS. TLC is useful to supplement seroagglutination for subtyping of MAC. Further study is required to determine whether apparent differences between isolates from patients with AIDS and from other sources reflect differences in virulence or in environmental prevalence of MAC subtypes. PMID- 8005219 TI - Comparison in the immunological properties of Borrelia burgdorferi isolates from Ixodes ricinus derived from three endemic areas in Switzerland. AB - Borrelia burgdorferi isolates were obtained from Ixodes ricinus from three sites in Switzerland. They were examined by SDS-PAGE and immunoblotting. The phenotypes, in respect of three outer surface proteins (Osp), differed between the sites of collection. In site 1, most isolates had an OspA of 31 kDa and an OspB of 34 kDa; in site 2, isolates presenting an OspA of 33 kDa dominated and in site 3, the isolates with an OspA of 32 kDa and an OspB of 35 kDa were most frequent. This distribution differed significantly. About half of the isolates from sites 1 and 3 reacted with anti-OspA monoclonal antibody H5332 compared to 29% from site 2. Site 1 isolates reacted significantly more frequently (81%) with another anti-OspA monoclonal antibody LA-31 than isolates from site 3 (P < 0.0001). These findings have implications for the epidemiology of Lyme borreliosis, for the further development of serodiagnostic reagents and for the development of a vaccine. PMID- 8005221 TI - Incidence and nature of peritoneal catheter biofilm determined by electron and confocal laser scanning microscopy. AB - Thirty-two Tenckhoff catheters retrieved from continuous ambulatory peritoneal dialysis patients with a history of peritonitis were examined for microbial biofilm. Confocal laser scanning microscopy was successfully employed to visualize bacteria in biofilm occluded from view by scanning electron microscopy. Occluded but viable microbial biofilm was associated with 17 (81%) catheters from patients free from infection following renal transplant. Mixed isolate biofilm with two or more isolates of coagulase-negative staphylococci or Staphylococcus aureus was found on 41% of these catheters. Clearly visible viable biofilm consisting exclusively of Pseudomonas aeruginosa occurred on all four catheters removed due to recurrent peritonitis. Five (71%) catheters retrieved from patients transferred to haemodialysis had viable biofilm. Antibiotic sensitivities of the biofilm isolates were similar in profile to those reported for non-biofilm isolates from infected dialysate. Persistence of catheter biofilm despite direct contact with therapeutic levels of antibiotics in peritoneal dialysate requires that attention be directed towards improving antibiotic efficacy against peritonitis-causing bacteria in biofilm form. PMID- 8005222 TI - An investigation of colonization of the conjunctival sac of sheep by bacteria and mycoplasmas. AB - The conjunctival sacs of 100 healthy adult ewes and 20 lambs and 76 adult ewes affected by ovine keratoconjunctivitis (OKC) were examined microbiologically. Branhamella ovis was the only organism regularly isolated from healthy ewes and lambs, Mycoplasma conjunctivae was isolated from the conjunctival sac of nine ewes but its occurrence was not associated with clinical signs of ovine keratoconjunctivitis. Mycoplasma conjunctivae and Branhamella ovis were isolated significantly more often from eyes affected by OKC than from unaffected eyes. PMID- 8005223 TI - Household-acquisition of measles and illness severity in an urban community in the United States. AB - Studies from developing countries suggest that persons with household-acquired (HA) measles are at greater risk of severe illness than persons with community acquired (CA) infection. Reported measles cases occurring among Milwaukee residents from May 1989 to June 1990 were used to assess whether household acquisition was a risk factor for severe measles in the United States. A case was classified as HA if onset of rash occurred 7-18 days after onset of rash in another case in the same household. Hospitalization rates were similar for 128 patients with HA measles (27%) and for 1004 patients with CA measles (26%). Multiple logistic regression was used to evaluate the association between hospitalization and household-acquisition after controlling for socioeconomic status, measles vaccination history, age, race, and date of onset of rash. Patients with HA measles were no more likely to be hospitalized than patients with CA measles (odds ratio 0.9, 95% confidence interval 0.6, 1.5). HA measles cases were not more severe than CA measles cases during this urban outbreak in the United States. PMID- 8005224 TI - A model-based design of a vaccination strategy against rubella in a non-immunized community of Sao Paulo State, Brazil. AB - A mixed vaccination strategy against rubella is proposed. We describe how the vaccination strategy was designed with the help of mathematical techniques. The strategy was designed for application in a non-immunized community of the State of Sao Paulo, Brazil, and was implemented by local health authorities in 1992. This strategy comprises a pulse vaccination campaign, covering the age interval between 1 and 10 years, followed by the introduction of the vaccine in the immunization calendar at 15 months of age. The expected impact of the proposed strategy is discussed. PMID- 8005225 TI - Risk factors for hepatitis C virus infection. A case-control study of blood donors in the Trent Region (UK). AB - The introduction of screening for hepatitis C virus (HCV) by the National Blood Transfusion Service identified donors who had acquired HCV infection. We undertook a case-control study amongst blood donors in the Trent Region to determine risks for HCV infection. A total of 74 blood donors confirmed positive for hepatitis C infection and 150 age, sex and donor venue matched controls were included in the study. Fifty-three percent of hepatitis C infected blood donors reported previous use of injected drugs compared to no controls; relative risk (RR) not estimatable (lower limit 95% CI = 20). Other risk factors were a history of: receipt of a blood transfusion or blood products RR = 3.6 (95% CI 1.5-8.3), having been a 'health care worker' RR = 2.8 (95% CI 1.1-7.6), tattooing RR = 3.3 (95% CI 1.2-8.7), and an association with having been born abroad RR = 3.2 (95% CI 1.1-9.5). No risk was shown for a history of multiple sexual partners, ear piercing or acupuncture. Injecting drug use explains more than 50% of hepatitis C infections in blood donors, a group who are less likely to have injected drugs than the general population. PMID- 8005226 TI - Recognition of adenovirus types in faecal samples by southern hybridization in South Australia. AB - The distribution of adenovirus types in faecal samples of patients with suspected viral gastroenteritis from South Australia was determined during the 12-month period, July 1991-June 1992. There were 3299 samples tested and 226 (6.9%) were positive for adenovirus by enzyme immunoassay. Of these 226 samples, 154 (68%) were typed directly using virus DNA extracted from the faecal samples according to the Sma I, Hind III and BstE II restriction patterns and Southern hybridization analysis with pooled viral genomic DNA probes. In this group, 86% of the samples were from patients who were < 3 years of age. Enteric adenovirus types 40 and 41 accounted for 20 and 40% respectively, of these samples, and types 1, 2, 3, 5, 6, 7 and 31 comprised the remainder. Type 40 was detected mainly in the winter and spring periods, and type 41 predominated in the autumn period. The majority of the non-enteric types were found during the late winter and spring periods. PMID- 8005227 TI - Survey on the distribution of the gene 4 alleles of human rotaviruses by polymerase chain reaction. AB - The presence of six gene 4 alleles (or VP4 genotypes) in human rotaviruses has been recognized. Using 16 representative cultivable human rotavirus strains, we confirmed the specificity of VP4 genotyping by polymerase chain reaction (PCR) using the nested oligonucleotides specific to each of the four representative gene 4 alleles. Using the PCR, we surveyed the gene 4 alleles of 199 human rotaviruses in stools collected in Japan and Thailand. Strains with the gene 4 allele, corresponding to P1A serotype, were shown to be the most prevalent, but two strains with P2 gene 4 allele and one strain with P3 gene 4 allele were detected in Thailand and in Japan, respectively. PMID- 8005228 TI - Distribution of bluetongue virus in Turkey, 1978-81. AB - Information about the distribution of bluetongue in Turkey during 1978-81 has been obtained by serological surveys in cattle, sheep and goats. The group specific immunodiffusion test was used to identify the presence of bluetongue virus (BTV) in a given province and the type-specific microneutralization test to decide which virus types had been in circulation. By drawing sera from accurately aged donor animals in May and August 1980, it was possible to draw up a general outline of the distribution of BTV in Turkey between early 1978 and mid 1980. By combining the same technique with spring and autumn field visits it became possible to make detailed inferences about the distribution of BTV serotypes in 1980 and 1981. The results support the conclusion that BTV was widespread in central and western Turkey for a number of years and suggests that overwintering can be a regular occurrence in that country. When compared with contemporaneous results from Syria and Jordan, a unifying and well-defined bluetongue virus ecosystem becomes apparent. PMID- 8005229 TI - Bernard-Soulier syndrome: quantitative characterization of megakaryocytes and platelets by flow cytometric and platelet kinetic measurements. AB - Platelets and megakaryocytes have been characterized in a Bernard-Soulier syndrome (BSS) kindred with respect to glycoprotein (GP) membrane receptors and measurements of thrombocytopoiesis. The index patient exhibited lifelong bleeding tendency, moderate thrombocytopenia (35 x 10(9)/l), giant platelets (mean platelet volume 12.5 microns 3 compared to 7.5 +/- 1.5 microns 3 in normals), absent ristocetin-induced platelet agglutination and absent binding of von Willebrand factor (vWF). Flow-cytometric analysis revealed absent platelet binding (0-2%) of monoclonal antibodies (mAb, LJ-P3, LJ-Ib1 and LJ-Ib10) directed against distinct epitopes on membrane GPIb alpha of the GPIb-IX complex, and normal binding of LJ-P4 mAb directed against GPIIb/IIIa complex (relative to increased platelet surface area). Marrow megakaryocytes also failed to express GPIb-IX complex, but demonstrated normal expression of GPIIb/IIIa. Among 6 asymptomatic family members, the patient's mother and 2 of his 4 children exhibited approximately 50% binding of anti-GPIb alpha mAb to their platelets by both flow cytometry and direct binding studies using 125I-vWF, 125I-LJ-Ib1 and 125I-LJ-Ib10 mAb. Marrow megakaryocytes were increased in the average cell volume and cytoplasmic granularity with a corresponding increase in ploidy (46% > 16N compared to 22 +/- 5% in normal individuals), a pattern typical of megakaryocytes stimulated by thrombocytopenia. Autologous 111In-platelet life span was shortened to 4.1 days (compared with 9.5 +/- 0.5 days in normal subjects), and the turnover of platelet mass in the circulation was near normal. The data directly demonstrate that the platelet membrane GPIb-IX defect in BSS originates in megakaryocytes at all levels of cell maturation, and exclude the possibility that the receptor abnormality is acquired during cell maturation or after platelets are released into the circulation. Since marrow megakaryocytes exhibited cellular changes consistent with stimulated megakaryocytopoiesis, these results also suggest that thrombocytopenia in this kindred of BSS is a consequence of both decreased platelet survival and ineffective platelet production. PMID- 8005230 TI - Role of protein phosphorylation in EPO-mediated early signal transduction: analysis in the EPO-reactive cell line ELM-I-1 transfected with a c-fos enhancer/promoter-luciferase reporter gene. AB - To investigate the role of protein phosphorylation in the early phase of EPO mediated signal transduction, we EPO-stimulated a murine erythroid cell line ELM I-1 transformed by plasmids comprised of the c-fos enhancer/promoter linked to the luciferase gene. Using this reporter gene system, we previously showed that EPO-induced activation of the c-fos promoter can be detected rapidly and sensitively as an elevation of cellular luciferase activity. In this study, we first examined the role of protein tyrosine phosphorylation. The tyrosine phosphatase inhibitor orthovanadate not only induced luciferase activity by itself but enhanced the action of EPO. On the other hand, the tyrosine kinase inhibitors erbstatin and herbimycin suppressed the effect of EPO. Next, the role of protein kinase C (PKC) in the EPO response was assessed. The PKC activator phorbol myristate acetate (PMA) not only induced luciferase activity by itself but enhanced the action of Epo. On the other hand, the PKC inhibitor 1-(5 isoquinolynyl-sulfonyl)-2-methylpiperazine (H7) suppressed the effect of Epo and PMA, whereas a nonspecific protein kinase inhibitor, N-(2-Guanidinoethyl)-5 Isoquinolinesulfornamine (HA1004) inhibited the action of neither Epo nor PMA. Another known PKC inhibitor staurosporine (STSP) did not inhibit but rather enhanced the effect of Epo. This action of STSP was blocked by H7 but not by HA1004. These results suggest that the EPO-mediated early signal transduction pathway leading to c-fos expression involves protein-tyrosine phosphorylation, is modulated by tyrosine phosphatase activity and is positively regulated by PKC. PMID- 8005231 TI - Comparison of younger versus older B-cell chronic lymphocytic leukemia patients for clinical presentation and prognosis. A retrospective study of 53 cases. AB - Fifty-three patients affected with B-cell chronic lymphocytic leukemia (CLL) younger than 50 years and observed in two hematological institutions have been retrospectively evaluated in order to verify whether this disease has different clinico-hematological features at presentation and different prognosis as compared to older cases. In our experience young cases with B-CLL diagnosis, confirmed by immunophenotype in 90.5% of patients, accounted for 7.1% of the whole CLL population. Sex distribution, mean peripheral lymphocyte count, platelet count, distribution among Rai's and Binet's stages, total tumor mass (TTM) score, histological pattern of bone marrow infiltration and lymphocyte doubling time (LDT) were similar to a series of 201 CLL cases older than 50 years. Only hemoglobin mean level was significantly higher in younger patients (13.1 +/- 2.1 vs 12.2 +/- 2.6 g/dl; p < 0.01). The overall median survival was 7.1 years. Rai and Binet staging classifications and TTM score system retained their prognostic value in this CLL population. In addition, cases fulfilling criteria of "smoldering" CLL, had a very long survival (75% survival probability at 16 years). Life-expectancy of younger patients was significantly longer than that of older ones (median survival, 7.1 versus 4.1 years; p < 0.05). However, when the background mortality due to non-CLL related deaths (i.e., cardiovascular complications, epithelial cancers) was removed, survival advantage of young cases disappeared. In conclusion this study confirms that prognosis of young CLL patients can be easily assessed using the current well-defined criteria. Since age is not by itself a criterion for intensifying treatment, further efforts to identify those young CLL patients who qualify for more aggressive therapy should be made. PMID- 8005232 TI - Vincristine sulfate for the treatment of thrombotic thrombocytopenic purpura refractory to plasma-exchange. The Italian Cooperative Group for TTP. AB - Among all the patients treated by the Italian Cooperative Group for TTP, we retrospectively reviewed the results obtained using vincristine (VCR) in 8 TTP patients (4 men and 4 women, average age: 39.25 years, range: 23-48) who did not respond to combined apheretic and pharmacologic treatment. All patients, after failing to respond to treatment, were started on VCR at the dose of 2 mg, i.v., once a week. Despite this treatment, 4 patients (50%) died 1, 7, 12 and 25 days after the first VCR dose, respectively. The other 4 patients who received VCR achieved complete remission 24, 30, 40 and 50 days from the beginning of the treatment. Total doses of VCR ranged from 2 to 6 mg in the decreased group, and from 6 to 14 mg in the cured patients. In our experience, VCR is a promising agent to treat TTP patients resistant to conventional plasma-exchange and pharmacologic therapy. PMID- 8005233 TI - Elevated serum homocysteine as a predictor for vitamin B12 or folate deficiency. AB - Tissue deficiency of vitamin B12 and folate results in an increase in serum homocysteine (sHcy). We have measured sHcy in patients with reduced serum vitamin B12 and/or red cell folate (RCF) to determine its usefulness as a discriminant for the diagnostic interpretation of reduced vitamin levels. Of 3846 patients who had serum vitamin B12 and RCF assayed, 335 (9%) had reduced vitamin levels. Multivariate analysis showed a significant association between sHcy and serum creatinine (p = 0.0001), positive intrinsic factor (IF) antibody or neutrophil hypersegmentation (NHS) (p = 0.001), increased MCV (p = 0.014) and low RCF (p = 0.025) but no relationship with the level of serum vitamin B12 or haemoglobin. After censoring the patients with renal impairment (n = 54), the distribution of the remaining 72 patients with elevated sHcy was 37/151 (25%) with low serum vitamin B12 with or without low RCF and 35/130 (27%) with low RCF alone. sHcy correctly identified response to vitamin therapy in 33/35 (94%) patients who had adequate parameters to assess response. The positive predictive values of IF antibody/NHS, macrocytosis and/or low RCF for elevated sHcy were 100% and 34% respectively. Twenty-four percent of patients with a low serum vitamin B12 and elevated sHcy had no abnormal haematologic parameters as determined by the routine laboratory staff. These data suggest that the usefulness of measuring sHcy in a routine diagnostic setting is limited and a careful review of the peripheral blood for macrocytosis and NHS plus determination of RCF may be a more cost-effective process than sHcy assay in most instances to determine the presence of tissue deficiency. PMID- 8005234 TI - Interferon treatment of refractory idiopathic thrombocytopenic purpura (ITP) AB - Up to 30% of patients with idiopathic thrombocytopenic purpura (ITP) are refractory to standard therapy with corticosteroids and splenectomy. The treatment of refractory ITP is barely effective, but promising results of interferon therapy were reported recently. In a prospective study 21 refractory ITP patients were treated with interferon alpha 2B at 3 million Units three times a week for a period of 4 weeks. Ten out of 21 patients had a response, of whom 2 had a complete response of 3.5 and 7 months duration, after which both relapsed. One other patient retreated after relapse has a complete response of 24+ months. The characteristics of the responding patients were not different from the non responding patients. Adverse effects were minimal. Short treatment with interferon in refractory ITP patients may be justified and the results reported here challenge us to elucidate the mechanism of action of interferon. PMID- 8005235 TI - Salvage therapy with low-dose cytosine arabinoside in refractory or relapsed acute non-lymphocytic leukaemia: a report on 25 patients. AB - Thirteen patients with de novo acute non-lymphocytic leukaemia (ANLL) refractory to standard chemotherapy for remission induction and 12 patients with ANLL in relapse were treated with low-dose cytosine arabinoside (LD ara-C) 10 mg/m2 subcutaneously every 12 hours for 21 days. Five of 13 patients (38%) and 6 of 12 patients (50%), respectively, obtained a complete remission (CR). Of these, 7 patients subsequently relapsed after 2-76 months, while 4 patients remain in CR after 7-131 months. Compared to standard intensive regimens treatment with LD ara C was rather non-toxic, requiring platelet transfusions and antibiotics in only 6 and 13 cases, respectively. Three patients (12%) died during induction therapy with LD ara-C; 2 had a cerebral haemorrhage and 1 developed anuria following a staphylococcal septicaemia. In conclusion, therapy with LD ara-C may be preferable to more intensive and toxic regimens in the treatment of patients with relapsed or refractory ANLL. PMID- 8005236 TI - An acquired Bernard-Soulier-like platelet defect in a patient with liver cirrhosis. PMID- 8005237 TI - Eosinophilia in patients with HIV-1 infection. PMID- 8005238 TI - Notable clinical changes of hepatosplenic abscesses in febrile neutropenic patients receiving empiric antifungal treatment with azoles. PMID- 8005239 TI - Congenital dyserythropoietic anemia type III with unbalanced globin chain synthesis. PMID- 8005240 TI - The fate of respiratory physiology. PMID- 8005241 TI - Prediction of disease progression in idiopathic pulmonary fibrosis. PMID- 8005242 TI - Outcome from mechanical ventilation. PMID- 8005243 TI - Clinical and functional assessment of patients with idiopathic pulmonary fibrosis: results of a 3 year follow-up. AB - The purpose of this study was to analyse the information provided by different techniques used in the assessment of patients with idiopathic pulmonary fibrosis (IPF) and their role in the prediction of lung function decline with the decline. Twenty seven subjects with IPF (55 +/- 14 (mean +/- SD) yrs) were studied at the initial staging. Nineteen of them (70%) were included in a follow-up over 3 yrs (32 +/- 6 months), whilst the remaining 8 patients were lost to follow-up. During the period of the study, 6 of the 19 patients died. A significant correlation between diffusing capacity of the lungs for carbon monoxide (DLCO) (and carbon monoxide transfer coefficient (KCO) = DLCO/alveolar volume (VA)) and the increase in alveolar-arterial oxygen tension difference (A-aPO2) during exercise (delta A aPO2) was observed at diagnosis (r = -0.58). Despite the treatment with prednisone (1 mg.kg-1 daily during 4 weeks, tapered to an individualized maintenance daily dose of 15-30 mg), the 13 patients controlled throughout the whole period of the study showed a marked impairment in lung volumes; forced vital capacity (FVC) -0.46 +/- 0.09 l, from 69 +/- 16 to 52 +/- 11% of predicted, and total lung capacity (TLC) -0.39 +/- 0.11 l, from 75 +/- 16 to 62 +/- 14%, and in DLCO -0.6 +/- 0.2 mmol.min-1.kPa-1, from 56 +/- 15 to 47 +/- 18%, predicted. By contrast, both mean arterial oxygen tension (PaO2) and A-aPO2 at rest remained unchanged throughout the 3 yrs follow-up.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8005244 TI - Mechanisms of increased epithelial lung clearance of DTPA in diffuse fibrosing alveolitis. AB - The aim of this study was to elucidate possible mechanisms of increased epithelial lung clearance in diffuse fibrosing alveolitis (DFA). We investigated the relationships between epithelial lung clearance as assessed by the clearance of aerosolized 99mTc-diethylene-triamine-penta-acetic acid (RC-DTPA), luminal alveolitis as assessed by bronchoalveolar lavage, and pulmonary function, in 30 nonsmokers with DFA. In 14 of these patients, RC-DTPA and lung function were determined before and during therapy with prednisolone (0.5 mg.kg-1 daily). RC DTPA was higher in patients with DFA (4.45 +/- 2.50%.min-1) than in normal subjects (1.18 +/- 0.31%.min-1). RC-DTPA did not correlate with the number of alveolar neutrophils, but correlated positively with the number of alveolar lymphocytes, and negatively with vital capacity (VC). RC-DTPA decreased from 6.1 +/- 2.8 to 3.8 +/- 1.9%.min-1 with prednisolone. RC-DTPA before prednisolone correlated positively with the prednisolone-associated improvement in VC. We conclude that in patient with DFA, RC-DTPA is increased, and decreases but does not return to normal with corticosteroid therapy. Our data suggest that in DFA the increase in RC-DTPA could be related to the recoil-induced stretch of the respiratory epithelium and to alveolar lymphocytic inflammation. PMID- 8005245 TI - Production of IL-1 and its receptor antagonist is regulated differently by IFN gamma and IL-4 in human monocytes and alveolar macrophages. AB - Interleukin-4 (IL-4) has previously been found to downregulate interleukin-1 (IL 1) production, but to upregulate the production of IL-1 receptor antagonist (IL 1ra) in human monocytes stimulated with lipopolysaccharide (LPS). In the present study we wanted to determine whether the production of IL-1ra in human monocytes and alveolar macrophages (AMs) is regulated differently at the protein and messenger ribonucleic acid (mRNA) levels by IL-4 and interferon-gamma (IFN gamma). AMs and monocytes obtained from healthy donors by bronchoalveolar lavage and centrifugal elutriation were stimulated with LPS in the presence or absence of IL-4 or IFN-gamma, and the expression of mRNA for IL-1 and IL-1ra was measured by Northern blot analysis. The production of IL-1 and IL-1ra was quantitated by enzyme immunoassays (EIAs). Spontaneous IL-1ra production was seen in AMs after incubation for 4 h in medium alone, but not in blood monocytes, at both the protein and mRNA levels. The spontaneous expression of the IL-1ra gene in AMs was augmented by incubation with IL-4. Interleukin-1 beta (IL-1 beta) production by LPS-stimulated AMs and monocytes was upregulated by IFN-gamma, but downregulated by IL-4. Interestingly, when stimulated with LPS, IFN-gamma inhibited IL-1ra production by monocytes, but up-regulated its production in human AMs at the protein and mRNA levels.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8005246 TI - Extent of centrilobular and panacinar emphysema in smokers' lungs: pathological and mechanical implications. AB - In order to quantify the extent of centrilobular (CLE) and panacinar (PLE) emphysema and the degree of the possible overlap between the two forms in smokers, the lungs of 25 smokers undergoing lung resection for peripheral lung tumours were studied. The extent of CLE and PLE was assessed by point counting, and the lungs were classified as having pure CLE (C, n = 5), predominant CLE with areas of PLE (CP, n = 7), predominant PLE with features of CLE (PC, n = 7), and pure PLE (P, n = 6) according to the percentage of lung involved by either form. Preoperative pulmonary function tests and the score of inflammation and the diameters of the small airways were also measured. Mean linear intercept (Lm), a measure of mean interalveolar wall distances and forced expiratory volume in one second (FEV1) were similar in the four groups. Small airway pathology was a predominant feature in lungs with CLE, and was significantly decreased in a stepwise fashion as the amount of PLE increased. This was especially so for the amount of muscle in the airway wall and the diameters of the airways. By contrast, lung compliance was higher in panacinar than in centrilobular emphysema.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8005247 TI - Pretransplant clinicopathological correlation in end-stage primary pulmonary hypertension. AB - The aim of the study was to see if there was any correlation between the histopathology, ultrastructure, pulmonary endocrinology and clinical manifestations of end-stage primary pulmonary hypertension. Twenty patients undergoing heart-lung transplantation for the disease were studied. The nature and duration of symptoms and signs, results of haematological, electrocardiographic, radiographic, echocardiographic and haemodynamic studies, and the response of patients to vasodilators were compared with data from histopathological and ultrastructural study of lungs removed at transplantation. Length of clinical history and clinical evidence of severe disease were not necessarily associated with advanced histopathology, nor did the presence of small, contracted muscular pulmonary arteries imply responsiveness to vasodilators. Numbers of gastrin-releasing peptide-containing pulmonary endocrine cells were greater in lungs in which there was activity of myofibroblasts in pulmonary arterial vessels, and correlated negatively with mean pulmonary artery pressure and pulmonary artery systolic pressure. Whereas the prognosis of primary pulmonary hypertension cannot as yet be defined by other than its clinical manifestations, intimal proliferation as well as vasoconstriction may be important in its pathogenesis. The release of gastrin-releasing peptide from pulmonary endocrine cells may possibly be involved in this process. PMID- 8005249 TI - Sendai virus infection changes the subcellular localization of tryptase Clara in rat bronchiolar epithelial cells. AB - Tryptase Clara activates the infectivity of Sendai and influenza viruses proteolytically. In this study, we investigated changes in the subcellular localization of tryptase Clara in rat bronchioles with progression of Sendai virus infection. Tryptase Clara and Sendai virus F2 antigen were localized by light and electron immunohistochemical studies. In the uninfected rat lung, tryptase Clara was specifically localized in the secretory granules of respiratory bronchiolar epithelial nonciliated cells, but not in bronchiolar ciliated, or alveolar cells. In the initial stage of Sendai virus infection with slight pathological changes, however, anti-tryptase Clara was highly reactive in luminal peripheral membranes of both nonciliated and ciliated epithelial cells of the bronchioles together with some Sendai virus envelope glycoprotein, F2 antigen. In the progressed stage, tryptase Clara was hard to detect, with heavy accumulation of F2 antigen in the epithelial cells. These immunohistochemical results support our previous findings that in the bronchial lavage fluid tryptase Clara is significantly increased both in amount and activity after viral infection. These results suggest that Sendai virus stimulates the secretion of tryptase Clara from nonciliated bronchiolar epithelial cells to the airway lumen. Accumulation of tryptase Clara on the luminal surface of the bronchiolar epithelial cells and/or in the airway lumen may produce favourable conditions for proteolytic viral activation and multiplication. PMID- 8005248 TI - Local antibodies against Pneumocystis carinii in bronchoalveolar lavage fluid. AB - Pneumocystis carinii pneumonia (PCP) is a frequent cause of pneumonia among human immunodeficiency virus (HIV)-infected patients. Little is known, however, about the role played by humoral immunity to control the infection. This study was undertaken to elucidate the role played by local antibodies. Bronchoalveolar lavage (BAL) fluids from 18 acquired immune deficiency syndrome (AIDS) patients with PCP, 20 HIV-antibody positive patients without PCP, and 20 lung cancer patients were examined for antibodies against P. carinii by the indirect immunofluorescence method. The ratio of albumin concentration in BAL fluid to serum was used to standardize the lavage fluids. Immunoglobulin G (IgG) antibodies against P. carinii occurred less frequently, and immunoglobulin M (IgM) antibodies more frequently, in PCP patients than in other groups. Immunoglobulin A (IgA) antibodies against pneumocysts were found with the same frequency in all three groups, although the median titre was lower among HIV antibody positive patients without PCP, compared with the other groups. When indexed (antibody titre in BAL fluid x albumin concentration in serum/antibody titre in serum x albumin concentration in BAL fluid) to express locally produced antibodies, IgG indices were significantly higher in HIV-infected patients without PCP, whereas IgM and IgA indices were significantly higher in PCP patients. These findings suggest that the local IgG response is impaired in patients with PCP, whereas the local IgA and, to some extent, the IgM responses are preserved. PMID- 8005250 TI - Effect of a mucoactive compound (CO 1408) on airway hyperreactivity and inflammation induced by passive cigarette smoke exposure in guinea-pigs. AB - Environmental exposure to tobacco smoke contributes to the onset of several lung diseases, e.g. chronic bronchitis and asthma, including an increase in airway reactivity. We have investigated the effect of a new mucoactive compound, CO 1408, on airway hyperreactivity and lung inflammation induced in guinea-pigs by passive cigarette smoke exposure. Animals were exposed to cigarette smoke in a Plexi-glass box, three times a day for four days. Airway reactivity to histamine was assessed ex-vivo in lung parenchymal strips. As a measure of lung inflammation, the number of leucocytes was evaluated in bronchoalveolar lavage (BAL) fluids and histological sections. Passive smoke exposure potentiated histamine-induced contraction in lung parenchymal strips, a phenomenon associated with an increase in proinflammatory cells in the BAL fluids and enhanced eosinophil infiltration into parenchymal tissues. Pretreatment with oral CO 1408 at 400 mg.kg-1 but not 100 mg.kg-1, completely prevented the cigarette smoke induced airway hyperreactivity. 400 mg.kg-1 CO 1408 also inhibited the increase in cell numbers in the BAL fluids, but not eosinophil recruitment in parenchymal tissues. The present data indicate the ability of CO 1408 to modulate smoke induced airway hyperreactivity and, to some extent, lung inflammation, an effect which might be of value in the therapy of obstructive pulmonary diseases. PMID- 8005252 TI - Factors affecting the long-term variability of bronchial responsiveness in an adult general practice population. AB - There have been few longitudinal studies of bronchial responsiveness. We wanted to assess the long-term variability and associations of bronchial responsiveness in the general population. Spirometry, bronchial provocation tests, skin-prick tests for allergy, and respiratory symptom questionnaires were repeated every 4 months, for 2 years (August 1987-August 1989), in 122 volunteers recruited from a cross-sectional survey of population. Provocation dose producing a 20% fall in forced expiratory volume in one second (PD20FEV1) and dose-response slope (SL), which gives values for methacholine responsiveness, were measured in all subjects. SL correlated well with PD20FEV1 but repeatability was impaired in those subjects with unmeasurably high PD20FEV1. The 95% range for repeatability of PD20FEV1 was +/- 3.11 doubling doses and +/- 4.52 doubling slopes for SL. Bronchial responsiveness increased in those with self-reported colds and reduced FEV1 in winter 1987-1988, and in males in winter 1988-1989. Bronchial responsiveness increased during the summer (June-August) of both years, significantly in year 1. We conclude that bronchial responsiveness showed minor seasonal variability and that colds were the strongest predictors of increased bronchial responsiveness over the 2 yr period. PMID- 8005251 TI - Effects of inhaled nitric oxide on methacholine-induced bronchoconstriction: a concentration response study in rabbits. AB - Inhaled nitric oxide (NO), at a concentration of 80 ppm, counters the increase in respiratory resistance (Rrs) induced by methacholine, but fails to prevent a reduction in lung compliance (Crs) in a rabbit model. This study reports the effects of 3, 30 and 300 ppm of inhaled NO. New Zealand White rabbits were intubated and mechanically ventilated with 30% oxygen during neurolept anaesthesia. Methacholine (3 mg.ml-1) was nebulized, with or without NO inhalation. Inhalation of 3 and 30 ppm NO had no effect on the induced bronchoconstriction, whereas 300 ppm fully blocked the increase in Rrs. The decrease in Crs due to methacholine was not countered by 3, 30 or 300 ppm NO. On the contrary, inhalation of 300 ppm NO in itself decreased Crs from 5.0 +/- 0.1 to 4.3 +/- 0.1 ml.cmH2O-1. Also, mean arterial pressure (60 +/- 7 to 54 +/- 5 mmHg), alveolar-arterial oxygen tension gradient (0.8 +/- 0.8 to 2.3 +/- 1.8 kPa) and methaemoglobin (0.5 +/- 0.2 to 1.5 +/- 0.5%) changed significantly on inhalation of NO 300 ppm prior to methacholine challenge. We conclude that 3 and 30 ppm NO inhalation does not alter methacholine-induced bronchoconstriction. Inhalation of 300 ppm NO blocks an increase in resistance but fails to counter the reduction in compliance due to methacholine. This suggests that the bronchodilating effects of NO in rabbits in vitro are confined to the large airways. PMID- 8005253 TI - Effect of beclomethasone dipropionate on bone mineral content assessed by X-ray densitometry in asthmatic children: a longitudinal evaluation. AB - There is little information on bone turnover in asthmatic children taking long term treatment with inhaled steroids (ICS). The aim of this longitudinal study was to determine the effects of inhaled beclomethasone dipropionate (BDP) on bone mineral density (BMD), in asthmatic children treated over a period of six months. BMD and growth were studied in two age- and sex-matched groups of asthmatic children. These comprised: 14 asthmatic children (Group 1) who had taken BDP in a dosage of 300-400 micrograms daily through a 145 ml spacer device for at least 6 months (mean age 9.1 yrs); and a control group of 16 age- and sex-matched asthmatic patients (Group 2) not treated with ICS (mean age 9.5 yrs). Mean duration of asthma was 5.7 yrs in Group 1 and 5.5 yrs in Group 2. Vertebral BMD (L2-L4) was measured by dual energy X-ray absorptiometry (DEXA) at the beginning (baseline) of the study and 6 months later. There were no significant differences in the baseline bone mass (mean +/- SEM) between the two groups (0.63 +/- 0.03 and 0.64 +/- 0.02 g.cm-2 in Group 1 and 2, respectively). During the observation period, bone density increased, by 4% (95% confidence interval (95% CI) 2-6) in the control group and by 2.3% (95% CI 0.4-4.2) in the group under BDP treatment, showing no significant influence of the treatment. No difference was found in height velocity evaluated before starting BDP and after 6 months of therapy.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8005254 TI - The opioid agonist codeine and antagonist naltrexone do not affect voluntary suppression of capsaicin induced cough in healthy subjects. AB - Opioids exert an analgesic action by mimicking the effects of endogenous neurotransmitter substances in the central nervous system. Opioids are widely used as antitussives, and it is reasonable to assume that endogenous opioids are involved in the control of cough. In order to investigate this hypothesis, a parallel design study was carried out to examine the effects of 50 mg codeine (opioid agonist), 50 mg naltrexone (opioid antagonist) and placebo on capsaicin induced cough in 80 healthy volunteers (mean age 25 yrs). Volunteers received two capsaicin challenge units (each consisting of five inhalations of different concentrations of capsaicin, 0.00-3.33 x 10(-4) M). On one challenge unit subjects were instructed to suppress cough, and on the other challenge unit subjects coughed freely. Coughs were recorded on a tape cassette player and later played back into a pen recorder to produce integrated sound traces. The number of coughs in the suppression challenge unit was significantly reduced in all three treatment groups compared to that recorded in the non-suppression challenge unit. Comparisons between the three treatment groups showed that there was no statistical difference between the three groups both before and 90 min after treatment for the total coughs in the suppression challenge unit and for the total coughs in the non-suppression challenge unit. These results demonstrate that capsaicin-induced cough can be voluntarily suppressed, but that both suppressed and non-suppressed cough were unaffected by treatment with codeine, naltrexone or placebo. These results do not provide any support for the hypothesis that capsaicin-induced cough is influenced by endogenous opioid substances. PMID- 8005255 TI - An out-patient nutritional supplementation programme in COPD patients. AB - Studies that have assessed the role of nutritional supplementation in patients with emphysematous chronic obstructive pulmonary disease (COPD) have shown conflicting results. Improved respiratory muscle strength and exercise capacity have been demonstrated following intensive and costly nutritional support programmes under controlled conditions. We have evaluated a simple programme of out-patient nutritional support in a clinical setting. Twelve malnourished COPD patients (9 male and 3 female; mean age 66 yrs; < 90% ideal body weight) were studied. Forced vital capacity (FVC), forced expiratory volume in one second (FEV1), estimation of maximal oxygen uptake (VO2max) during exercise, respiratory muscle strength (PImax and PEmax), and measurement of body weight, height, triceps skinfold thickness, and mid-arm muscle circumference were performed before and after a 4 month period of out-patient nutritional support. Patients were advised by a dietician on increasing their daily caloric intake by a minimum of 50% above estimated daily energy expenditure. Three patients withdrew from the study. The mean increase in body weight in the nine remaining patients after 4 months of supplementation was 0.3 kg. There was no significant improvement in the anthropometric measures, lung function, respiratory muscle strength or VO2max for the group as a whole. Three patients who gained more than 1 kg weight were from a higher socioeconomic background compared with those who failed to do so. We conclude that achieving weight gain and improving lung function by means of simple out-patient nutritional programmes in a clinical setting is difficult. PMID- 8005256 TI - Factor analysis of exercise capacity, dyspnoea ratings and lung function in patients with severe COPD. AB - In this study we aimed to determine the relationship between exercise capacity, clinical ratings of dyspnoea and lung function parameters in patients with severe chronic obstructive pulmonary disease (COPD) by means of the statistical method of factor analysis. Sixty two patients (mean age +/- SD, 66 +/- 9 yrs) in stable clinical condition, with a forced expiratory volume in one second (FEV1) < 65% of predicted were investigated. Before the study, therapy was optimized, including inhaled bronchodilators, theophylline and steroids. Exercise capacity was determined from the best 6 min walking distance achieved in five self-paced treadmill walks performed on consecutive days. Lung function testing comprised spirometry and body plethysmography. Four different tools were chosen to rate dyspnoea and quality of life: the Baseline Dyspnoea Index (BDI), the Oxygen Cost Diagram (OCD), a modified Medical Research Council (MRC) Scale, and the Chronic Respiratory Disease Questionnaire (CRQ). Principal component factor analysis revealed that the data could be reduced to three hypothetical underlying variables (factors), which accounted for 79% of the total variance. BDI, MRC, OCD, CRQ and walking distance were attributed to the first factor, forced expiratory volume in one second and airway resistance to the second factor, and lung volumes to the third factor. Thus, our data suggest that the pathophysiological condition of severe COPD is characterized by three statistically independent entities: 1) exercise capacity, dyspnoea and quality of life ratings; 2) airway obstruction; and 3) pulmonary hyperinflation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8005257 TI - Arterial oxygenation does not predict the outcome of patients with acute respiratory failure needing mechanical ventilation. AB - One hundred and eighteen patients consecutively submitted to mechanical ventilation during a one year period, and admitted to the Respiratory Intensive Care Unit of the Hospital Clinic of Barcelona, were prospectively studied in order to define the importance of hypoxaemia as a predictor of mortality. Using a discriminant multivariate analysis, the following variables were selected as the best predictors of outcome: 1) the number of associated complications (NAC) on admission; 2) the simplified acute physiologic score (SAPS); 3) oxygenation index (PAO2-AaPO2)/PAO2 + 0.014 positive end-expiratory pressure (PEEP); and 4) the age of the patients. Using these predictors, 84% of the patients were accurately classified as survivors or as nonsurvivors. The partial contribution of each predictor to the model was also assessed using a logistic regression, by eliminating each single predictor and each possible pair of predictors. Using this means of analysis, the NAC and SAPS were the only predictors of mortality. The inclusion of short-term mechanically-ventilated patients did not bias the accuracy of prediction. PMID- 8005258 TI - Use of budesonide Turbuhaler in young children suspected of asthma. AB - The question addressed in this study was the ability of young children to use a dry-powder inhaler, Turbuhaler. One hundred and sixty five children suspected of asthma, equally distributed in one year age-groups from 6 months to 8 yrs, inhaled from a Pulmicort Turbuhaler, 200 micrograms budesonide-dose-1, through a filter. The amount of drug trapped by the filter was used as a measure of drug released to the patient. None of the children had prior experience in the use of a Turbuhaler, but they were instructed carefully, together with their parents, in the clinic. The median dose released revealed an age-dependent increase, with a considerable scatter. Accordingly, the dose delivered could not be predicted in these young children. The limitation to effective use in young children appeared to be lack of sufficient co-operation, rather than physical limitations, as even some very young children appeared to obtain a sufficient activation of the device. It is likely that repeated training at home may improve these findings. In conclusion, our results indicate that dry-powder inhalers are not reliable in all circumstances for treatment of young children, and that careful and repeated tuition is required if such devices are to be used. PMID- 8005259 TI - Pulmonary immune cells in health and disease: the eosinophil leucocyte (Part II). AB - The second part of this review on eosinophils focuses on biological cell functions and surveys the various deleterious mechanisms involved in the eosinophil-dominated inflammatory reaction. It discusses the possible pathogenic role of eosinophils in several eosinophil-related diseases, such as parasitic infections, interstitial lung disorders and bronchial diseases, such as parasitic infections, interstitial lung disorders and bronchial diseases, graft rejection, vasculitic granulomatous disorders, pleural effusion, and bronchogenic tumours. The final section of the article highlights the possible recent pharmacological and future therapeutic approaches in modifying eosinophil recruitment and function. PMID- 8005260 TI - Prognosis of occupational asthma. AB - Several studies on the prognosis of occupational asthma have shown that a significant proportion of patients continue to experience asthmatic symptoms and nonspecific bronchial hyperresponsiveness after cessation of work. The determinants of this unfavourable prognosis of asthma are: long duration of exposure before the onset of asthma; long duration of symptoms before diagnosis; baseline airway obstruction; dual response after specific challenge test; and the persistence of markers of airway inflammation in bronchoalveolar lavage fluid and bronchial biopsy. The relevance of immunological markers in the outcome of occupational asthma has not yet been assessed. Further occupational exposure in sensitized subjects leads to persistence and sometimes to progressive deterioration of asthma, irrespective of the reduction of exposure to the specific sensitizer, and only the use of particular protective devices effectively prevents the progression of the disease. A long-term follow-up study of toluene diisocyanate (TDI)-induced asthma showed that the improvement in bronchial hyperresponsiveness to methacholine occurred in a small percentage of subjects and only a long time after work cessation. Bronchial sensitivity to TDI may disappear, but non-specific bronchial hyperresponsiveness often persists unchanged, suggesting a permanent deregulation of airway tone. Steroid treatment significantly reduces nonspecific bronchial hyperresponsiveness only when started immediately after diagnosis. PMID- 8005261 TI - Prevention of occupational asthma. AB - This paper focuses on the prevention of asthma caused by exposure to sensitizing agents in the workplace. Control of exposure (primary prevention) is the most direct method of reducing the number of incident cases. Screening programmes are also necessary as a "safety net", and have value as secondary prevention, because early detection may improve long-term prognosis. It is recommended that regulatory or advisory bodies with responsibility for occupational asthma publish a guidance document on occupational asthma explaining their current concepts. Surveillance activities provide information on how common asthma is relative to other occupational lung diseases, and on the relative frequency of occurrence of asthma caused by different agents. Publication of a list of sensitizing agents would aid those with responsibility for control of exposure in the workplace. Epidemiological research on exposure-response relations is is necessary as a background to prevention. This paper recommends such studies. Immunotoxicological research also has a role in testing hypotheses that cannot be tested in human subjects. Some standardization of screening programmes in industry is desirable. A short symptoms questionnaire is economical and acceptable to workers, but there are other approaches. Finally, evaluative research on prevention measures gives information on their effectiveness and efficiency. PMID- 8005263 TI - The cardiovascular effects of obstructive sleep apnoeas: analysis of pathogenic mechanisms. AB - Obstructive sleep apnoeas (OSA) exert immediate marked cardiovascular effects, and may favour the development of systemic and pulmonary hypertension in the long term. As for the pathogenesis of the acute cardiovascular changes, the first studies high-lighted the role of OSA-induced hypoxia and mechanical changes. However, more recent work pointed to the role played by the arousal reaction terminating OSA, and to the activity of the autonomic nervous system during apnoea and inter-apnoeic phase. As for the pathogenesis of chronic cardiovascular changes, recent findings suggest that the link between OSA and systemic hypertension may be through an abnormal function of the carotid body and underline the importance of chronic intermittent hypoxia versus continuous hypoxia in the development of stable systemic hypertension. On the other hand, OSA do not appear to enhance strongly the development of stable pulmonary hypertension. In this review, we analyze OSA-induced cardiovascular changes with particular emphasis on to the interplay of the possible pathogenic mechanisms involved. Acute OSA-induced cardiovascular alterations during the apnoeic phase appear to result mainly from the mechanical effects of OSA, while during the interapnoeic phase they seem mostly determined by chemical factors (hypoxia, hypercapnia) and by the arousal reaction. In addition, the role of reflex changes elicited by resumption of ventilation should be reconsidered, since lung inflation seems to exert a positive effect on the cardiovascular changes occurring at the end of OSA. This would be in contrast with the inhibitory effects described as "lung inflation reflex", and deserves further study. PMID- 8005262 TI - From granuloma to fibrosis in interstitial lung diseases: molecular and cellular interactions. AB - Granuloma is a feature of many chronic interstitial lung diseases, and may serve as a focus for subsequent fibrosis. Granulomas are composed of structured masses of cells of the macrophage lineage, which adopt an epithelioid aspect, interspersed with lymphocytes. They are formed around local centres of irritation. During their resolution, fibroblasts congregate around the structures and may penetrate the interior. In many cases, granulomas can disappear without leaving lasting traces. However, especially when damage has occurred to the surrounding tissue, permanent scarring and fibrosis may occur. Both types of cell present in the granuloma are capable of secreting a number of factors influencing the accumulation and proliferation of fibroblasts, both positively and negatively. The possible roles played by the different factors and, especially, interactions between them are discussed in the light of fibrosis formation. Possible therapeutic interventions are summarized. PMID- 8005264 TI - Statistical approaches to the identification of late asthmatic reactions. AB - Late asthmatic reactions can be difficult to recognize because of their prolonged time course and the confounding effects of superimposed circadian rhythms of ventilatory function. Conventional methods of analysis are rather arbitrary. They depend for example on a 15 or 20% fall in forced expiratory volume in one second (FEV1) from baseline or from time-matched control measurements. We have, therefore, investigated whether statistical approaches applied to individual subjects can assist in the identification of late asthmatic reactions. In two separate series of aerosol inhalation tests, three symptomatic workers, three asthmatic controls and three nonasthmatic controls were challenged blindly with increasing doses of two chemical agents, and saline. One of the agents, sodium isononanoyl oxybenzene sulphonate (SINOS) was a suspected cause of occupational asthma. Prior to the challenges, FEV1 was measured hourly on three control days. Cumulative late changes on both control and active challenge days were quantified as the area between a line extrapolated from a 10.00 h baseline and the actual measurements from 12.00-22.00 h (the 2-12 h area decrement). The area decrement measurements on control and active challenge days were compared using Student's t tests. The sensitivity of this method for detecting late asthmatic reactions among potentially positive tests (SINOS challenge tests in the workers) was examined, as was its specificity. The latter was determined from the false positive rate among the negative tests. A second statistical method based on the pooled standard deviation of serial (hourly) FEV1 measurements was investigated in the same way. In total, the data from 220 challenge and 30 control days were available for analysis.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8005265 TI - Precision and accuracy of Morgan ventilometers at continuous and sinusoidal flows. AB - The P.K. Morgan Mark II Ventilometer comprises a turbine transducer and a control/readout unit, which contains either a VENTX5A or VENTX6A programme. This equipment is used to measure minute ventilation during oxygen consumption tests. The precision and accuracy of six of these devices (a VENTX5A with two turbines, and two VENTX6As each with two different turbines) were examined during continuous and pulsatile flows; accuracy was affected by the syringe rate during the calibration procedure. The reference standard was a 350 l Collins chain compensated gasometer. At continuous flows, the two VENTX5A devices showed accuracies of 99.5-100.5% over the range 60-160 l.min-1 whereas those for the four VENTX6As were 99.3-102.1% over the range 60-200 l.min-1. The mean accuracies of sinusoidal flows for the VENTX5A ranged between 96.1-101.3% for minute volumes spanning 15-200 l.min-1; comparable data for the VENTX6As were 95.9-98.9%. These mean accuracies improved to 98.1-101.3% for the VENTX5A at measured minute volumes > 80 l.min-1. Omission of the two lowest tidal volumes (1 and 1.5 l) for the VENTX6As narrowed the range of accuracy to 96.9-98.5%. The coefficients of variation for five trials at each minute ventilation were 0-0.2%. We conclude that, while the P.K. Morgan Mark II Ventilometer has excellent precision, its accuracy is dependent on the calibration syringe rate, minute ventilation and program. PMID- 8005266 TI - Bronchiolitis obliterans: the lone manifestation of rheumatoid arthritis? AB - The patient was a 62 year old man, who suddenly developed obstructive lung disease without a readily definable cause. He had a remarkable family history of deforming rheumatoid arthritis, and a serum rheumatoid factor of 1:1,256, but with no evidence of active rheumatological disease. Clinical, physiological and radiologic features suggested bronchiolitis obliterans, and this was confirmed by open lung biopsy. Immune staining of tissue revealed immunoglobulin M (IgM) as well as rare immunoglobulin (IgG) containing plasma cells in a peribronchiolar location. Because of these findings, we suggest that this case represents bronchiolitis obliterans secondary to a rheumatoid process. This case is unusual since it appeared in a man and is the first and, so far, the only manifestation of rheumatoid arthritis. Prior studies indicate that the bronchiolitis obliterans of rheumatoid arthritis occurs primarily in women and only in ongoing cases. PMID- 8005267 TI - IVOX in ARDS: respiratory effects and serious complications. AB - We describe the beneficial effects of an intravenous oxygenator (IVOX) on ventilatory pressure requirement, and also several severe complications related to its use in a young trauma victim developing severe acute respiratory distress syndrome (ARDS). In this patient, adequate systemic oxygenation could not be maintained despite the use of fractional inspired oxygen of 1.0, high level positive end-expiratory pressure (PEEP), and nitric oxide inhalation (30 ppm). The introduction of an intravenous oxygenator improved arterial oxygenation and CO2 elimination, allowing a decrease in minute ventilation and airway pressure. However, hepatic cytolysis, acute renal dysfunction and iliac vein thrombosis developed concomitantly, in spite of full anticoagulation with heparin. These complications resolved rapidly after removal of the IVOX device and the patient made a good recovery. PMID- 8005268 TI - Successful treatment of AIDS-related pulmonary Kaposi's sarcoma with liposomal daunorubicin. AB - We report a 35 year old male, human immunodeficiency virus (HIV)-infected patient with acquired immune deficiency syndrome (AIDS), who presented with rapidly progressive pulmonary Kaposi's sarcoma. The tumour regressed with treatment with liposomal daunorubicin and remained in partial remission until the patient died 12 months later from complications of HIV infection. Liposomal daunorubicin may be a safe and effective alternative to the treatment protocols in current use for pulmonary Kaposi's sarcoma. PMID- 8005269 TI - A rare case of inflammatory pseudotumour of the bronchus, occurring in an achondroplastic woman. AB - An inflammatory pseudotumour of the lung in an achondroplastic woman is described. The occurrence of both conditions in the same patient probably represents a coincidental finding. However, recurrent pulmonary infections, as frequently seen in achondroplasia, may be relevant, because a history of antecedent infection is noted in one third of cases of inflammatory pseudotumours. Despite extensive debridement of the pseudotumour by neodymium yttrium aluminium garnet (NdYAG) laser therapy, early recurrence occurred. PMID- 8005270 TI - Airway inflammation in symptomatic and asymptomatic children with methacholine hyperresponsiveness. PMID- 8005271 TI - Report of a workshop assessing the risks and benefits of inhaled anti inflammatory treatment for asthma. PMID- 8005272 TI - Amenorrhea during the reproductive years--is it safe? AB - OBJECTIVE: To collate information relating specifically to amenorrhea of different etiologies in young women, the long- and short-term implications of these states, and the optimal therapeutic strategy to treat these conditions. DATA IDENTIFICATION: Studies related to these topics were identified through literature and Medline searches. STUDY SELECTION: Those studies that relate specifically to amenorrhea in women of reproductive age, including etiology, diagnosis, and the implications of replacement therapy or nontreatment of this state, were selected. RESULTS: Amenorrhea, as defined by the absence of menses for > or = 6 months, may be found in up to 3% of women in the reproductive years. Classification of amenorrhea involves defining the exact cause for the cessation of menses, be it hypothalamic, pituitary, ovarian, or lower genital tract in origin. The majority of amenorrheic young women have very low levels of estrogens, and a minority will have subnormal noncyclic estrogen levels, unopposed by P, due to anovulation. This distinction is important in considering the long-term implications of amenorrhea. Hypoestrogenic amenorrhea is associated with a significant loss of bone mineral density and the associated risk of osteoporosis and fractures. Lipoprotein profiles are also adversely affected, and this is associated with an increased risk of cardiovascular events. Anovulatory amenorrhea due to "unopposed" estrogen is associated with an increased risk of endometrial hyperplasia and endometrial carcinoma even in young patients. Therapy should be aimed at treating the underlying cause of amenorrhea, if possible, or reconstitution of an estrogen-P biphasic monthly cycle if not. CONCLUSIONS: Untreated amenorrhea is associated with significant long-term morbidity, especially in young women. Early recognition and institution of treatment will minimize late complications. PMID- 8005273 TI - The effect of estradiol depletion during the luteal phase on endometrial development. AB - OBJECTIVE: To examine whether luteal E2 is obligatory for obtaining an adequately developed endometrium. DESIGN: Survey of women with premature ovarian failure (POF) in a prospective, controlled, randomized study. SETTING: In vitro fertilization unit in a tertiary care university medical center. PATIENTS: Fourteen amenorrheic women with POF, candidates for oocyte donation, were divided into two distinct groups with seven women in each subgroup. INTERVENTIONS: Endometrial priming with a fixed dose of oral micronized E2, 4 mg/d for 14 days, was similarly performed in the study and the control groups. Progesterone replacement during the luteal phase was also identical in the two groups and was accomplished by IM P in oil, 50 mg/d for another 14 days. Only the control group continued to have the same E2 regimen during the luteal phase. MAIN OUTCOME MEASURES AND RESULTS: Follicular phase mean E2 levels as well as luteal phase mean P levels were similar in both groups. However, luteal E2 levels differed significantly between the study and the control groups (21 +/- 5 and 692 +/- 199 pg/mL, respectively; conversion factor to SI units, 3.671). Nevertheless, histologic evaluation of endometrial biopsies on days 21 and 26 were similar for both groups. Endometrial gland dating, using light microscopy in the study and the control groups, on day 21, was 19.1 +/- 0.8 and 18.4 +/- 0.5, respectively, and on day 26, 25.4 +/- 0.8 and 25.9 +/- 0.5, respectively. Dating of the stroma in the two biopsies was also similar in both groups. Moreover, transmission electron microscopy performed in two patients of the study group showed typical characteristics of a secretory endometrium. CONCLUSIONS: Luteal E2 depletion in the human does not seem to adversely affect the morphological developmental capacity of the endometrium. Our results suggest that E2 secretion by the corpus luteum in the human does not appear to be obligatory for the development of a normal secretory endometrium. The actual receptivity of the endometrium after such preparation needs to be evaluated. PMID- 8005274 TI - The effect of progesterone administration in the follicular phase of an artificial cycle on endometrial morphology: a model of premature luteinization. AB - OBJECTIVE: To evaluate the effect of premature P administration on artificially prepared endometrium in women with ovarian failure. DESIGN: To mimic premature luteinization, patients with ovarian failure were treated with continuous estrogen and episodic P during the follicular phase of artificial cycles. SETTING: In vitro fertilization unit at a university hospital. PATIENTS: The study group included 16 patients with ovarian failure who were randomly divided into two groups. Group A (8 patients) was treated by episodic P administration during the artificial follicular phase on days 2 and 7 (12.5 mg of P in oil IM), and in group B (8 patients), P (6.25 mg) was added on days 3, 4, and 5. Another 16 patients (group C), age matched to the study group, were arbitrarily allocated to serve as controls and had standard preparatory cycles without P supplementation in the follicular phase. Serum E2 and P levels and endometrial biopsies were taken on days 14 and 26. RESULTS: Serum E2 levels were comparable between the study group (group A+B) and controls on both days 14 and 26. Although serum P levels did not differ between the groups on day 26, it was higher in the follicular phase of the study group than in the controls (1.9 +/- 4.0 and 0.2 +/- 0.1 ng/mL, respectively). In the study group, 8 of 16 patients demonstrated early secretory changes in the late follicular phase biopsies, and 9 of 16 women developed stromal-glandular discrepancy in the late luteal phase. This differed significantly from the controls in which only one late luteal biopsy was out of phase. CONCLUSIONS: Episodic surges of P during the follicular phase may result in impaired endometrial development that cannot be corrected by P supplementation during the luteal phase. This unique model provides evidence for the potential detrimental effect of premature P secretion in the follicular phase on endometrial function. PMID- 8005276 TI - Comparison between depot and standard release triptoreline in in vitro fertilization: pituitary sensitivity, luteal function, pregnancy outcome, and perinatal results. AB - OBJECTIVE: To compare the effects of depot and standard release form of triptoreline in superovulation induction in IVF programs. DESIGN: One hundred ninety-six patients undergoing IVF were randomized between two treatment groups. Pituitary desensitization was obtained in group 1 (102 patients) with a single IM injection of 3.75 mg D-Trp-6-luteinizing hormone-releasing hormone (LH-RH) and, in group 2 (94 patients), with daily SC administration of 0.1 mg D-Trp-6-LH-RH. In a subgroup of 11 patients, a series of GnRH tests was performed to investigate pituitary desensitization and, in another subgroup of 12 patients, a study of luteal phase steroid profile was performed. In an additional 23 patients, a series of GnRH tests were performed to investigate pituitary desensitization during the late follicular and midluteal phases. RESULTS: No differences were found in the time necessary to reach desensitization (11.3 +/- 1.03 versus 11.3 +/- 1.45 days; mean +/- SEM), whereas resumption of pituitary activity takes place in 7 days after the discontinuation of the daily form and in about 2 months after discontinuation of the depot form. No differences were found in the duration of stimulation, number of FSH ampules, E2 levels, and number of follicles (11.7 +/- 0.68, versus 12.2 +/- 0.68) on hCG administration day and the total oocytes collected (9.1 +/- 0.6 versus 9.2 +/- 0.64). Oocyte quality, percentage of fertilization and cleavage, pregnancy rate per transfer (28.7% versus 25.6%), and miscarriages (about 30%) were similar in the two protocols. No difference was found in hormonal levels during the luteal phase. In both groups there was a high incidence of multiple pregnancy. CONCLUSION: Comparable results can be achieved with both long-acting and standard-release forms of GnRH analogs in patients undergoing assisted reproduction in terms of follicular stimulation and abortion rates despite differences in the duration of pituitary suppression. PMID- 8005275 TI - The role of estrogen support during the luteal phase of in vitro fertilization embryo transplant cycles: a comparative study between progesterone alone and estrogen and progesterone support. AB - OBJECTIVE: To evaluate the possible role for estrogen supplementation to the P luteal phase support of GnRH agonists (GnRH-a)- and hMG-induced IVF-ET cycles. SETTING: In vitro fertilization unit in a tertiary care university hospital. DESIGN: A prospectively randomized study. PATIENTS: One hundred consecutive patients undergoing ET after IVF were assigned into one of two luteal supplementation regimens. INTERVENTIONS: In all patients enrolled in the study, ovulation was induced using the midluteal regimen for pituitary down regulation with GnRH-a followed by follicular stimulation with hMG. The first group received IM P 50 mg/d, as luteal phase support, starting the day of ET. The second group received the same dosage of P, combined with oral E2 valerate, 2 mg/d. Serum levels of P and E2 were monitored every 4 days for 16 days after ET. MAIN OUTCOME MEASURES: Pregnancy rates (PRs) and live birth rates per ET. RESULTS: No significant difference in E2 or P levels throughout the cycle was observed between groups. Similar PRs per ET and the live birth rates were also observed between group A and B (28% versus 26.5% and 78.6% versus 76.1%, respectively). CONCLUSION: No advantage was found in the addition of E2 valerate to P luteal phase support of GnRH-a- and hMG-induced IVF-ET cycles. PMID- 8005277 TI - Is paracervical block anesthesia for oocyte retrieval effective? AB - OBJECTIVE: To quantitate pain relief associated with paracervical local anesthesia during transvaginal ultrasound-guided collection. DESIGN: The study was a prospective, randomized, double-blinded, placebo-controlled, and no treatment-controlled investigation. Pain scores for vaginal pain associated with entry into the cul-de-sac and global assessment for the entire procedure were generated separately by patient and physician. Variables evaluated include duration of procedure, patient weight and age, total number of vaginal and ovarian "follicular" punctures, number of oocytes retrieved, and amount of IV medication. SETTING: A private IVF-ET program. PATIENTS: Women in an IVF-ET program who volunteered to join the study (n = 101). INTERVENTIONS: Local anesthesia as a paracervical block compared with placebo or no injection during transvaginal oocyte retrieval, with all patients receiving IV sedation. RESULTS: Both vaginal and global pain scores, whether patient or physician assessed were lower for paracervical block than placebo. Agreements between physician and patient assessments of pain scores were close. Duration of the procedure was correlated with pain score. In general, a placebo effect on pain perception compared with no injection was not seen. CONCLUSION: Paracervical local anesthesia compared with placebo injection was associated with lower pain scores for both vaginal puncture and global assessment of the oocyte retrieval process but was not significantly better than no injection for global evaluation. PMID- 8005278 TI - Intravenous albumin for the prevention of severe ovarian hyperstimulation syndrome in an in vitro fertilization program: a prospective, randomized, placebo controlled study. AB - OBJECTIVE: To evaluate the efficacy of i.v. administration of human albumin solution for the prevention of severe ovarian hyperstimulation syndrome (OHSS). DESIGN: A prospective, randomized, placebo-controlled study comparing the effects of i.v. administration of human albumin solution versus sodium chloride 0.9% solution at the time of oocyte retrieval with patients undergoing IVF-ET who are at high risk for the development of severe OHSS. SETTING: Specialized assisted reproduction unit. PATIENTS: Thirty-one patients undergoing IVF-ET who had serum E2 levels of 1,906 pg/mL (> 7,000 pmol/L) and multiple follicular development on the day of hCG administration. INTERVENTIONS: After hCG administration, patients were randomized to receive i.v., either 50 g of human albumin diluted in 500 mL of sodium chloride 0.9% or 500 mL of sodium chloride 0.9% at the time of oocyte retrieval. MAIN OUTCOME MEASURES: Ovarian size as measured by pelvic ultrasonography, development of ascites, serum E2 concentrations during the luteal phase, and results of the IVF-ET cycles. RESULTS: Although no patient who had received human albumin solution developed severe OHSS, there were four such cases in the control group. All four were hospitalized with marked ascites and ovarian enlargement. There were no significant differences between the two groups comparing serum E2 levels on the day of hCG administration and during the luteal phase, the number of oocytes retrieved, fertilization, and pregnancy rates. CONCLUSIONS: Our preliminary results suggest that the administration of human albumin solution may help to prevent the development of severe OHSS in high-risk patients. Further research is needed to assess the potential of this novel approach. PMID- 8005279 TI - Association of elevated estradiol with remote testicular trauma in young infertile men. AB - OBJECTIVE: To determine the incidence of remote testicular trauma and of possible related permanent hormonal and seminal changes in infertile men. DESIGN: Retrospective clinical study of hormonal and seminal parameters in a subpopulation of infertile men. SETTING: Andrology Clinic in an academic research environment. PARTICIPANTS: Infertile men, with and without history of remote testicular trauma, and fertile volunteers. MAIN OUTCOME MEASURES: Percentage of infertile men with history of blunt testicular trauma, concentrations of reproductive hormones, and semen parameters. RESULTS: Significant remote blunt testicular trauma was reported by 16.8% of infertile men. This had occurred 2 to 17 years (mean, 16.4 years) before evaluation, mostly with contact sports at adolescent age. Estradiol concentrations after testicular trauma were 19% and 25% higher than in infertile men without history of testicular injury and in fertile controls. Elevated E2 levels did not correlate with T. Infertile men with and without history of testicular trauma showed changes in seminal parameters. CONCLUSION: The incidence of remote blunt testicular trauma in infertile men is unexpectedly high. After injury, FSH-stimulated aromatization of T may increase testicular E2 production, interfere with spermatogenesis, and cause infertility. Consistent use of protective devices in contact sports is recommended. PMID- 8005280 TI - The relationship between total motile sperm count and the success of intrauterine insemination. AB - OBJECTIVES: To determine if the total motile sperm count is predictive of IUI success and to apply life-table analysis to a large database of IUI procedures. DESIGN: Contingency table and life-table analyses were used to analyze a large group of couples (n = 546) undergoing 1,205 cycles of therapeutic IUI with husband's sperm. SETTING: Clinical infertility practice at a medical school referral center. PATIENTS: Five hundred forty-six couples with varying etiologies of infertility. RESULTS: There was a trend toward an increasing percentage of conception with increasing total motile sperm count. Significance was reached when the total motile sperm count used for IUI exceeded 20 x 10(6). The cumulative pregnancy rate calculated from this data reached 52% after the sixth attempted cycle of IUI. PMID- 8005281 TI - Testicular secretion after pulsatile human menopausal gonadotropin therapy in gonadotropin-releasing hormone agonist desensitized dysspermic men. AB - OBJECTIVE: To evaluate Leydig and Sertoli cell response to prolonged pulsatile stimulation with hMG after pituitary desensitization with the GnRH agonist (GnRH a) triptoreline in normogonadotropic men with abnormal semen analyses. DESIGN: A group of four oligozoospermic men were investigated in the following manner: [1] basal and GnRH-hCG stimulated activity were assessed in all volunteers; [2] a long-acting form of the GnRH-a triptoreline (3.75 mg every month for 3 months) was given, and its effectiveness was evaluated on day 20; and [3] on that day hMG pulsatile administration was introduced (150 IU per 24 hours in 90-minute pulses) with serial hourly sampling (6 to 7 hours) for measurement of FSH, LH, T, E2, and inhibin on days 20, 41, and 90 from the first GnRH-a injection. RESULTS: Initial evaluation showed normal basal, GnRH, and hCG-stimulated hormone concentrations. Pituitary and gonadal activity were effectively suppressed by GnRH-a when tested on day 20. Pulsatile hMG had no immediate stimulatory effect on gonadal activity (day 20). However, on middle and final evaluations (days 41 and 90), basal T, E2, and inhibin had risen to pre-GnRH-a levels, and, moreover, distinct secretory pulses were seen for these hormones. CONCLUSION: These findings indicate that suppression of pituitary gonadotropin activity with triptoreline combined with pulsatile hMG stimulation offers a new, useful tool for investigation of the male reproductive system in oligozoospermic men. PMID- 8005282 TI - The effect of testicular nongerm cell tumors on local spermatogenesis. AB - OBJECTIVE: To assess ipsilateral spermatogenesis in men with malignant and benign nongerm cell tumors of the testis. DESIGN, PATIENTS: Histologic review of radical orchiectomy specimens performed for 20 men with malignant nongerm cell tumors and 15 with benign testicular lesions, including five Leydig cell tumors with benign clinical features. MAIN OUTCOME MEASURES: Degree of spermatogenesis was determined on a 1 to 10 scale, with 10 representing mature sperm within a seminiferous tubule. For each patient "near" and "far" scores were determined by obtaining the mean score of 50 tubules adjacent (< 3 mm) to the tumor and 50 tubules distant (> 3 mm) from the tumor, respectively. RESULTS: Total, near, and far scores were all lower for malignant tumors than for benign lesions. Scores for Leydig cell tumors were similar to benign lesions. Malignant tumors demonstrated a gradient effect, with greatest impairment of spermatogenesis occurring adjacent to tumor. In contrast, a distinction between near and far scores was not observed for benign lesions or Leydig cell tumors. CONCLUSIONS: Malignant nongerm cell tumors of the testis were associated with significant impairment of ipsilateral spermatogenesis, particularly in areas adjacent to tumor. These findings are similar to those observed for testicular germ cell tumors, suggesting a generalized negative influence on ipsilateral spermatogenesis by malignant tumors. PMID- 8005283 TI - Sperm-immunobead binding decreases with in vitro incubation. AB - OBJECTIVE: To characterize the stability of the sperm-immunobead association over time. DESIGN: Prospective evaluation of sperm-immunobead binding, using direct and indirect assays. SETTING: Male Infertility Clinic, University of California, Davis, Davis, California. PATIENTS: Eleven men with sperm surface antibodies and 25 men with serum antisperm antibodies volunteered. MAIN OUTCOME MEASURES: Repeated assessment of sperm-immunobead binding over time. RESULTS: Serum immunoglobulin (Ig)G decreased a mean of 42.6% over 30 minutes, and serum IgA decreased a mean of 22.7% over 30 minutes. Semen-derived IgG binding fell a mean of 59.9% and semen-derived IgA fell a mean of 27.0% over 25 to 40 minutes. CONCLUSIONS: Sperm-immunobead coincubation results in a decrease in the number of sperm bound to immunobeads. PMID- 8005284 TI - On the future of the hamster oocyte penetration assay. PMID- 8005285 TI - The effect of preincubation of human spermatozoa in milk on sperm penetration into zona-free hamster oocytes and on sperm binding to the human zona pellucida. AB - OBJECTIVE: To determine whether preincubation of sperm in milk enhances the outcome of sperm penetration assay (SPA) and hemizona assay (HZA) when compared with preincubation in TES and Tris (TEST)-yolk. DESIGN: Sperm penetration assay and HZA were performed on milk and TEST-yolk preincubated spermatozoa. INTERVENTIONS: Ejaculates were washed and divided into two equal aliquots. An equal volume of heat-inactivated cow's milk (95 degrees C, 10 minutes) was added to one aliquot and an equal volume of TEST-yolk was added to the other aliquot. Both sperm mixtures were cooled slowly to 5 degrees C and incubated for 2 hours. They were then washed twice (400 x g for 8 minutes) with culture medium at 37 degrees C and processed for SPA and HZA. MAIN OUTCOME MEASURES: Percentage of oocytes penetrated and the penetration index for the SPA. The number of sperm bound to hemizona and hemizona index for the HZA. RESULTS: Sperm preincubated in milk yielded significantly higher SPA results and hemizona index when compared with TEST-yolk. The penetration index and the number of sperm bound were high but were not statistically significant. CONCLUSION: Preincubation of sperm in milk enhances the SPA and HZA outcome when compared with TEST-yolk. PMID- 8005286 TI - Frozen-thawed cumulus-granulosa cells support bovine embryo development during coculture. AB - OBJECTIVE: To evaluate the ability of bovine cumulus-granulosa cells to survive cryopreservation and subsequently support bovine embryo development during coculture. DESIGN: In vitro-matured and -fertilized bovine embryos (two- to four cell) were allotted randomly to one of three treatment groups: [1] control medium alone consisting of Medium 199 containing 10% fetal bovine serum and antibiotics, [2] cocultured on fresh bovine cumulus-granulosa cells in control medium, or [3] cocultured on frozen-thawed cumulus-granulosa cells in control medium. Embryo development was assessed on days 7 and 8 after IVF. RESULTS: Coculture improved embryo development on days 7 and 8 compared with the control group. However, embryo development on days 7 and 8 did not differ among coculture groups. CONCLUSIONS: Frozen-thawed cumulus-granulosa cells enhance embryo development similar to fresh cells during in vitro coculture. PMID- 8005287 TI - The influence of pentoxifylline (Trental) on the antifertility effect of intrauterine devices in rats. AB - OBJECTIVE: To test the hypothesis that the inflammatory response stimulated by intrauterine devices (IUDs) plays a role in the antifertility action of IUDs. We treated rats with pentoxifylline (Trental; Hoechst-Roussel Pharmaceuticals, Inc., Somerville, NJ) and evaluated its effect on the anti-implantation action of IUDs. The number of embryos in treated compared with untreated rats was determined. DESIGN: Breeder female Sprague-Dawley rats (Harlan Sprague Dawley, Indianapolis, IN) were randomized into one of five test groups (n = 20 per group). A monofilament nylon IUD was inserted transcervically into one horn of the bicornuate uterus in two groups. The IUD-bearing groups received either intraperitoneal (IP) injections of pentoxifylline (45 mg/kg per every 12 hours) or normal saline (NS). The two non-IUD-bearing groups received IP injections of pentoxifylline or NS. The non-IUD group was not injected. All injections were administered daily for 21 days and the animals then mated. Successful mating was determined by the presence of spermatozoa in vaginal washings. The injections of pentoxifylline or NS were continued until day 12 of pregnancy when the rats were killed. The total number of embryos in each uterine horn was determined. SETTING: University research laboratory. RESULTS: Embryo numbers (1.0 +/- 0.6 [mean +/- SEM]) were reduced in the IUD horn compared with the contralateral non-IUD horn (6.4 +/- 1.0) and with the uterine horns from each of the four other test groups. The number of embryos were increased in the IUD horn (3.5 +/- 0.9) of the pentoxifylline-treated rats. CONCLUSION: Pentoxifylline appeared to reduce the contraceptive effectiveness of the IUDs in this model. PMID- 8005288 TI - Cytokines stimulate lipid membrane peroxidation of human sperm. AB - Reactive oxygen species production has been demonstrated to impair sperm function. We have noted the potential for the cytokines IL-1 alpha, IL-1 beta, and TNF alpha to stimulate reactive oxygen species production by fertile donor sperm at levels that are consistent with the levels of IL-1 occurring in human seminal plasma. Reactive oxygen species-related sperm membrane peroxidation may be one mechanism by which cytokines can exert a detrimental effect on male fertility. This study suggests a new mechanism by which cell-mediated immunological male infertility may occur. PMID- 8005289 TI - Ovarian hyperstimulation syndrome associated with the use of the gonadotropin releasing hormone agonist leuprolide acetate. AB - Severe ovarian hyperstimulation syndrome occurred after the administration of LA to suppress multicystic ovaries. It is possible that this patient with multiple ovarian cysts, each 2 to 3 cm in size, is at increased risk for a paradoxical stimulatory rather than inhibitory response to GnRH-a. PMID- 8005290 TI - Endometrial responses to three different progestins in artificial cycles: a prospective, crossover study. AB - We found that there was no significant difference in endometrial responses to vaginal or IM P. But the response was suboptimal in cycles treated with dydrogesterone, suggesting that dydrogesterone treatment is not the preferred progestin for use in artificial cycles. PMID- 8005291 TI - Reproductive potential after treatment for persistent ectopic pregnancy. AB - We examined the success rate and reproductive outcome of 50 patients who had been treated for persistent EP after initial unsuccessful salpingostomy. All who underwent salpingectomy had successful treatment of their persistent EP. One treatment failure occurred after MTX. Of 50 women, 32 (61.5%) attempted conception after treatment for persistent EP. The cumulative clinical pregnancy rate after treatment for persistent EP was 59% at 36 months. There was a significant association between clinical pregnancy rate after persistent EP and those with normal contralateral fallopian tubes (P < 0.005). The relative risk of having a clinical pregnancy among those who attempted conception was 2.3 for those having a normal contralateral fallopian tube compared with those with a contralateral fallopian tube with obvious pathology. Intrauterine pregnancy rates after treatment of persistent EP were similar to those reported for primary treatment of EP. PMID- 8005292 TI - Menstrual asthma: use of a gonadotropin-releasing hormone analogue for the treatment of cyclic aggravation of bronchial asthma. AB - A new clinical indication for GnRH-a treatment seems to exist in addition to the many indications known so far. The successful treatment of cyclic severe attacks of bronchial asthma during ovulation and the menstrual periods with a GnRH-a is described. A 45-year-old woman with long-standing bronchial asthma was hospitalized because of severe bronchial asthma and status asthmaticus 11 times during the 5 months before her referral. The hospitalizations were either during the ovulatory or menstrual period, and in two of them they were so grave to require artificial ventilation through an endotracheal tube. To induce pituitary ovarian desensitization and amenorrhea, the patient was put on monthly injections of depot GnRH-a, which she has been receiving for the last 20 months. Subjective improvement was accompanied by a significant improvement in spirometric indices, by lack of hospitalizations, and decrease in glucocorticoid daily dosage. Although a trial of sequential add-back HRT was unsupportable because of respiratory aggravation, low-dose continuous HRT was tolerated by the patient. In light of the dramatic subjective and objective improvement in association with the GnRH-a treatment, we conclude that this new application deserves further experience. PMID- 8005293 TI - The climacteric ovary as a functional gonadotropin-driven androgen-producing gland. AB - OBJECTIVE: To assess the hypothesis that the climacteric ovary is a functional endocrine gland. DESIGN: Review of the English-speaking literature as it relates to the physiology and pathophysiology of the climacteric ovary. RESULTS: By several accounts, the climacteric ovary appears to be a gonadotropin-dependent androgen-producing gland. Although the estrogen-producing potential of the climacteric ovary remains a matter of controversy, most studies would suggest limited aromatase activity. CONCLUSIONS: [1] The climacteric ovary is not a defunct endocrine organ. [2] The climacteric ovary is a site of gonadotropin reception and action. [3] The climacteric ovary contributes few if any estrogens to the circulating pool by way of direct production. [4] Circulating estrogens are derived virtually exclusively from the extraglandular conversion of androgens, a proportion of which are of ovarian origin. [5] The climacteric ovary contributes 40% and 20% of the total production rates of T and androstenedione, respectively. [6] Androgen biosynthesis by the climacteric ovary is partially gonadotropin-dependent. PMID- 8005294 TI - Response of the endosalpinx to potential irritants. PMID- 8005295 TI - A novel transportation system and incubator. PMID- 8005296 TI - Skills for tubal catheterization. PMID- 8005297 TI - Role of growth hormone in ovulation induction. PMID- 8005298 TI - Potency differences in GnRH antagonists? PMID- 8005299 TI - Decibel activity--leukocytes versus immature germ cells. PMID- 8005301 TI - Gonadotropin-releasing hormone agonist versus human chorionic gonadotropin as a trigger of ovulation in polycystic ovarian disease gonadotropin hyperstimulated cycles. AB - OBJECTIVE: To compare the use of GnRH agonist (GnRH-a) versus hCG in triggering the follicular rupture in patients with polycystic ovarian disease (PCOD) in whom ovulation was induced by gonadotropins. DESIGN: Polycystic ovarian disease gonadotropin hyperstimulated cycles outcome was investigated in a prospective study. PATIENTS AND INTERVENTIONS: Thirty-three PCOD patients (40 cycles) with gonadotropin-induced mild to moderate degree of ovarian hyperstimulation received 5,000 IU IM hCG or 200 microg [corrected] SC GnRH-a. A subgroup of GnRH-a-treated patients received P for luteal support. Five GnRH-a-treated patients underwent a GnRH test during luteal phase. MAIN OUTCOME MEASURES: Echographic and endocrine characteristics both during the therapy and the luteal phase. RESULTS: There was a similar percentage of ovulation and pregnancy rate in both groups of patients. The ovarian enlargement during the luteal phase in the GnRH-a-treated patients was lower than in the hCG group. Progesterone plasma levels (at midluteal phase) and the length of luteal phase was significantly lower in GnRH-a-treated patients with respect to the hCG-treated group. These differences disappeared in patients receiving luteal support. After GnRH injection, LH secretion decreased in GnRH-a treated patients with respect to controls; however, corpus luteum was able to respond with a normal increase of P production. CONCLUSION: The GnRH-a appears to be an effective alternative to hCG for inducing the follicular rupture in stimulated cycles in women who are at risk for developing ovarian hyperstimulation syndrome. However, GnRH-a administration can induce short luteal phase. This defect may be ascribed to the pituitary desensitization rather than to a direct effect on corpus luteum. Luteal phase support is needed to prevent luteal phase deficiency. PMID- 8005300 TI - The antiprogestin RU486 delays the midcycle gonadotropin surge and ovulation in gonadotropin-releasing hormone-induced cycles. AB - OBJECTIVE: To investigate whether the antiprogestin RU486 acts primarily on the hypothalamus to delay the midcycle gonadotropin surge and thus gain insight into the site(s) of action of P in the control of ovulation. DESIGN: Prospective, crossover, single-blinded clinical study. SETTING: Outpatient clinic in an academic research environment. PATIENTS: Women with hypothalamic amenorrhea. INTERVENTIONS: RU486 or a placebo was given orally at a low dose of 1 mg/d for 5 days, starting when the dominant follicle reached 14 to 16 mm, to women with hypothalamic amenorrhea undergoing ovulation induction with GnRH pulses of unvarying frequency and dose. Blood samples and ovarian ultrasounds were obtained daily in the late follicular phase and every 3 to 4 days in the remainder of the cycle. MAIN OUTCOME MEASURES: Follicular diameter and plasma levels of LH, FSH, E2, and P. RESULTS: RU486 consistently delayed the timing of the midcycle gonadotropin surge and ovulation. Gonadotropin and steroid levels were suppressed during RU486 treatment, but follicular growth progressed normally in most patients. CONCLUSIONS: RU486 does not act primarily on the hypothalamus to delay ovulation. Rather, this compound appears to antagonize P at the pituitary level to suppress gonadotropin and steroid hormone secretion. P may thus act on the pituitary, independent of any hypothalamic effects, to regulate the timing of the midcycle gonadotropin surge and ovulation. PMID- 8005302 TI - Cycle abnormalities in infertile women with regular menstrual cycles: effects of clomiphene citrate treatment. AB - OBJECTIVE: To investigate the incidence and nature of cycle abnormalities and the effect of clomiphene citrate (CC) treatment in women with apparently ovulatory cycles and unexplained infertility. DESIGN: Nonrandomized, open study of patients before and during treatment. SETTING: The Reproductive Medicine Clinic of a District General Hospital. PATIENTS: Thirty-five women with regular, apparently ovulatory menstrual cycles and unexplained infertility. INTERVENTIONS: Detailed ultrasound and hormonal cycle tracking was performed before and during treatment with CC. MAIN OUTCOME MEASURES: Serial ultrasound scans and measurements of serum LH, FSH, E2, and P. RESULTS: Before treatment, 54% of cycles were uniovulatory, 40% were characterized by cyst formation, and 6% were characterized by poor follicular growth. Fifty-one percent of pretreatment cycles had normal hormone profiles, 31% had defective luteal phases, 14% had increased early follicular phase serum FSH levels, and 9% had increased early follicular phase serum LH levels. Treatment with CC reduced the incidence of cyst formation to 9% and the incidence of luteal phase defects to 3%. However, 28% of CC-treated cycles showed ultrasound features of overstimulation and 51% had high follicular phase E2 peaks so that only 34% of CC-treated cycles had normal hormone profiles. CONCLUSIONS: Cycle abnormalities are common in unexplained infertility. The incidence of cyst formation and luteal phase defects, the most common abnormalities in this group, is reduced by CC treatment. PMID- 8005303 TI - Transvaginal ultrasonic assessment of the response to clomiphene citrate in polycystic ovarian syndrome. AB - OBJECTIVE: To study the relationship between some ovarian morphological findings based on transvaginal ultrasound (US) and the clomiphene citrate (CC) responsiveness in patients with polycystic ovarian syndrome (PCOS). DESIGN: A comparative study of ovarian US features between the CC responders and the CC nonresponders. SETTING: Infertility and Endocrine Clinic, Department of Obstetrics Gynecology, Shimane Medical University Hospital, Izumo, Japan. PATIENTS: Forty-seven infertile patients with PCOS and 30 healthy volunteers. INTERVENTIONS: A dose of 50 to 200 mg/d CC was given for ovulation induction in patients with PCOS. MAIN OUTCOME MEASURES: Ovarian volume and number of follicles; serum LH, FSH, T, delta 4 androstenedione, and DHEAS. RESULTS: The mean ovarian volume (11.9 mL) and the number of small follicles (13.0) were significantly larger in the CC nonresponders compared with those of the CC responders (7.9 mL and 7.0, respectively). Only 47% of the CC responders and 79% of the CC nonresponders had bilaterally enlarged ovaries (> 6.2 mL). Considerable overlap existed between the different groups. However, 96% of the CC nonresponders had a significantly increased number of follicles (> or = 10 follicles) in each ovary compared with that (16%) of the CC responders. Furthermore, with the combination of these parameters, none of the CC nonresponders had bilaterally normal ovaries, and 96% of patients with PCOS with bilaterally abnormal ovaries were CC nonresponsive. CONCLUSIONS: Small multiple follicles (> or = 10) and enlarged ovarian volume (> 6.2 mL) were the most prominent transvaginal US features of ovaries in patients with PCOS with CC nonresponsiveness. These US features could be clinically useful for distinguishing clearly a CC nonresponder from a CC responder. PMID- 8005304 TI - Luteal phase defect: the sensitivity and specificity of diagnostic methods in common clinical use. AB - OBJECTIVE: To assess the sensitivity and specificity of common clinical tests used for the diagnosis of luteal phase defect (LPD). DESIGN: The sensitivity and specificity of these tests for predicting low integrated P levels over the luteal phase were calculated. SETTING: Outpatient reproductive endocrinology and infertility clinic at a university medical center. PATIENTS: Fifty-eight strictly defined normal women were used to determine normal integrated luteal phase P levels. The study population was a separate 34 women who either were normal (n = 15) or were being evaluated for infertility or recurrent abortion (n = 19). These 34 study subjects all had the following tests performed in the same menstrual cycle: daily reproductive hormone levels, daily assessment of preovulatory follicle size, late luteal endometrial biopsies, and BBT charts. MAIN OUTCOME MEASURES: Basal body temperature, maximum preovulatory follicle size, dated endometrial biopsies, and serum P levels (single and multiple) were used in an attempt to predict which patients had low integrated P levels. RESULTS: Unacceptably low sensitivity and/or specificity levels were found for the following tests: appearance of BBT charts, luteal phase length, and preovulatory follicle diameter. Timed endometrial biopsy was found to have marginally acceptable sensitivity and specificity levels whether dated by next menstrual period or midcycle events. The best test for the prediction of low integrated P was a single serum P level from the midluteal phase that was < 10 ng/mL (31.8 nmol/L) or a sum of three random serum P measurements that was < 30 ng/mL (95.4 nmol/L) (also obtained in the midluteal phase). CONCLUSIONS: Luteal phase defect is a relatively uncommon but important cause of infertility and/or habitual abortion. The recommended test for the determination of LPD is a midluteal phase single serum P level < 10 ng/mL or the sum of three serum P levels that is < 30 ng/mL. The endometrial biopsy is a second line test that is only recommended when LPD needs to be evaluated in a treated cycle (ovulation induction or supplemental P). PMID- 8005305 TI - Ovarian endometrial cysts: the role of gonadotropin-releasing hormone agonist and/or drainage. AB - OBJECTIVE: To evaluate the role of GnRH agonist (GnRH-a) and/or drainage in the management of large endometriomas. DESIGN: This prospective clinical study was conducted in a parallel and randomized design. SETTING: Department of Gynecology, Cliniques Universitaires St. Luc, Brussels, Belgium. PATIENTS: Eight infertile women with laparoscopically confirmed ovarian endometriotic cysts. After laparoscopic drainage of the ovarian cyst, patients were randomized. Patients in group I (n = 40) received no therapy. Patients in group II (n = 40) received GnRH a therapy for 12 weeks. A second-look laparoscopy was performed after 12 weeks in each woman. RESULTS: After drainage, a quick recurrence of the endometrial cyst was observed in only group I. Indeed, the score and the cyst size were similar to the values observed before the first laparoscopy. In group II, a significant decrease in score and cyst diameter was observed. Ovarian biopsies revealed significant reduction in the stromal vascularization and a significant reduction in the mitotic activity in the group of women treated with GnRH-a. CONCLUSION: The quick recurrence of the ovarian cyst after drainage proved that drainage alone is ineffective. Drainage followed by GnRH-a was effective in the reduction of cyst size and the glandular mitotic activity. PMID- 8005306 TI - A comparison of pain experienced during hysterosalpingography and in-office falloposcopy. AB - OBJECTIVE: To determine patient perception of the intensity of pain during in office falloposcopy compared with hysterosalpingography (HSG). DESIGN: A prospective quality assurance study using a formal pain scale to compare two procedures. SETTING AND PATIENTS: Patients attending a tertiary level infertility clinic. INTERVENTIONS: In-office falloposcopy or HSG using analgesics. MAIN OUTCOME MEASURES: The mean pain score and area under the pain curve experienced during each investigation. RESULTS: Using our technique, in-office falloposcopy was associated with a significantly lower mean intensity of pain and with a longer procedure. The duration of the falloposcopic examination declined significantly with physician experience. Flushing adjacent to the uterotubal ostium, ostial cannulation, and rapid eversion provoked episodes of acute pain during falloposcopy. CONCLUSION: These results support the patient acceptability of in-office falloposcopy. PMID- 8005307 TI - Association of time to pregnancy and the outcome of pregnancy. AB - OBJECTIVE: To examine the relationship of subfertility with miscarriage, low birth weight, and preterm delivery. DESIGN: Comparison of time to pregnancy distributions between pregnancies that had different outcomes. Three comparisons were made: (a) miscarriages with live births; within live births, (b) low birth weight infant (up to 2,500 grams) or not low birth weight; (c) preterm birth (37 weeks or less) or not preterm. Cox regression was used to adjust for covariates. POPULATION: All first pregnancies were analyzed from the National Child Development Study, a large survey of young adults aged 33 years, which is nationally representative of the British-born population. MAIN OUTCOME MEASURES: The distribution of the time taken to conceive (time to pregnancy), miscarriage, birth weight, and preterm delivery. RESULTS: Pregnancies that ended in miscarriage tended to take 23% longer to conceive, after adjustment for the other variables. Pregnancies that resulted in preterm delivery tended to take 15% longer to conceive. There was no statistically significant association with low birth weight. CONCLUSIONS: Delay in time to conception is a risk factor for poor obstetric outcome, irrespective of medical intervention. PMID- 8005308 TI - Serum levels of androstanediol glucuronide, total testosterone, and free testosterone in hirsute women. AB - OBJECTIVE: To determine the serum levels of androstanediol glucuronide (3 alpha diol G), total T, and free T in hirsute and nonhirsute women. DESIGN: Controlled clinical study. PATIENTS: Hirsute women with oligomenorrhea, hirsute women with regular ovulatory cycles, and nonhirsute women with regular cycles were selected. MAIN OUTCOME MEASURE: Serum levels of 3 alpha-diol G, total T, and free T were measured in 8 hirsute with oligomenorrhea and 11 hirsute women with regular ovulatory cycles and compared with 20 nonhirsute women with regular cycles (control group). Serum 3 alpha-diol G was also measured during the follicular, periovulatory, and luteal phases in hirsute women with regular cycles. RESULTS: Serum levels of 3 alpha-diol G did not change during the menstrual cycle, in addition we observed that there was no difference between the levels of 3 alpha diol G, total T, and free T in hirsute women with regular cycles when compared with normal women. These three serum androgens were elevated only in the hirsute women with oligomenorrhea. Besides, there was better correlation between total T and free T (r = 0.81) than total T and 3 alpha-diol G (r = 0.49) or free T and 3 alpha-diol G (r = 0.66). CONCLUSION: The findings suggest that serum 3 alpha-diol G does not provide additional benefit as a marker of hirsutism than serum total or free T. PMID- 8005309 TI - Scoring system for prediction of ovarian endometriosis based on transvaginal color and pulsed Doppler sonography. AB - OBJECTIVE: To develop a new noninvasive scoring system using clinical signs and symptoms, CA-125 levels, sonographic findings, and transvaginal color and pulsed Doppler parameters for preoperative recognition of ovarian endometriosis. DESIGN: A 5-year prospective study in patients undergoing laparotomy and laparoscopy. SETTING: Department of Obstetrics and Gynecology, University of Zagreb, Sveti Duh Hospital, Zagreb, Croatia. PATIENTS: Six hundred fifty-six benign and malignant adnexal masses, among which 103 were surgically proved to be ovarian endometriosis. INTERVENTIONS: All patients undergoing laparotomy and laparoscopy were examined by transvaginal ultrasonography with color Doppler imaging. Serum levels of CA-125 were measured the day before surgery. MAIN OUTCOME MEASURE: The total score was applied in all patients with adnexal masses. RESULTS: The scoring system proved to be very useful in distinguishing ovarian endometriosis from other benign and malignant ovarian lesions, with a sensitivity of 99.02% and a specificity of 99.64%, compared with morphological scoring system's sensitivity of 83.91% and specificity of 97.12%. CONCLUSION: The new noninvasive scoring system improves significantly the ability to discriminate between endometriosis and other benign and malignant ovarian entities. PMID- 8005310 TI - Effect of danazol in vitro and in vivo on monocyte-mediated enhancement of endometrial cell proliferation in women with endometriosis. AB - OBJECTIVE: To investigate danazol's effect in vitro and in vivo on the ability of peripheral blood monocytes (PBM) from women with endometriosis to stimulate endometrial cell proliferation. DESIGN: Uterine endometrial cells from untreated or danazol-treated patients with endometriosis were cultured with or without autologous or heterologous PBM in the presence of different concentrations of danazol for 72 hours before assessment of endometrial cell proliferation by thymidine incorporation. SETTING: Not for profit clinical research institute and academic cell culture laboratory. PATIENTS: Women of reproductive age undergoing laparoscopy for endometriosis, 19 untreated patients and 17 danazol-treated patients. INTERVENTIONS: Peripheral blood monocytes and endometrial biopsies obtained at laparoscopy. Danazol (800 mg/d) administered for 2 to 6 months (treated group) or added to cell cultures in concentrations of 10(-6), 10(-7), or 10(-9) M. RESULTS: Endometrial cell proliferation was enhanced by autologous or heterologous PBM from untreated patients with endometriosis but was unaffected or suppressed by PBM from danazol-treated patients. Danazol in vitro reduced PBM enhanced endometrial cell proliferation. Endometrial cell proliferation from danazol-treated patients was not enhanced by PBM from untreated patients with endometriosis. CONCLUSIONS: Danazol treatment in vitro or in vivo suppresses PBM mediated enhancement of endometrial cell proliferation. The effects are against both PBM and endometrial cells, suggesting that danazol affects monocyte-derived growth-stimulating factors and endometrial cell response to growth-stimulating factors. PMID- 8005312 TI - [Variations of pathological tooth loss with special reference to tooth erosion- apropos of a case]. AB - Importance of tooth surface loss has increased in dental practice. It is difficult to determine aetiological factors and the exact diagnosis, because the symptoms are often combined. The aim of the present study was to summarise the most important factors of tooth surface loss, mainly of erosion which is a frequent form. Reviewing the literature aetiological factors, symptoms, differential diagnostic problems and therapeutic advice are discussed. Prevention, early diagnosis and treatment are very important in these patients. PMID- 8005311 TI - Dating the endometrial biopsy by flow cytometry. AB - OBJECTIVE: To determine endometrial changes throughout the menstrual cycle. DESIGN: Flow cytometric analysis of endometrial cells versus chronological dating. SETTING: Women volunteers with a normal menstrual cycle participated in this study that was done in an academic research environment. PATIENTS: Two hundred thirty regular menstruating women with adequate luteal phase underwent endometrial biopsy at different days of their menstrual cycle; 138 biopsies were analyzed both histologically and by flow cytometry. MAIN OUTCOME MEASURE: Percentage of biopsies correctly classified in terms of chronological dating. RESULTS: Flow cytometry correctly classified the chronological day of biopsies in 59% of cases, the proliferative versus secretory days in 91% of cases, and the early, mid, and late secretory phases of the menstrual cycle were correctly predicted in 86% of cases. CONCLUSION: Flow cytometry is a good method to determine growth and differentiation of the endometrium during the menstrual cycle. Detection of phases of the whole endometrial cell population offer information on the biological adequacy of endometrial response to the biochemical environment. PMID- 8005313 TI - [An instrument for positioning elastic ligatures (ligature instrument)]. AB - The ligature instrument is constructed for placing in position elastomeric ligatures. The instrument has two types--one designed for fore-teeth area and one for premolars and molars--traditional or ergonomical aspects were taken into consideration with metal or sterilizable plastic handle. This instrument fills a long felt gap because to complete this process until now no such type of special instrument existed. PMID- 8005314 TI - [Stomatologic mass screening in the 3rd District of Budapest]. AB - Stomatooncological examinations, related to the lung-screening process in the 3rd district of Budapest have been performed for one and a half year. Screening examinations of 2213 non-selected patients identified precancerous lesions in 127 cases: leukoplakia in 5.74%, oral lichen in 0.36%. Fifty-seven percent of the patients never or only in painful cases visited the dentist. Based on their findings, the authors claim to continue this screening program, and recommend the extension of this model to the whole population. PMID- 8005315 TI - [Simultaneous occurrence of four primary malignant tumors in a patient]. PMID- 8005316 TI - [A single central maxillary incisor in the midline as a mild form of holoprosencephaly]. AB - Besides the hypotelorism the mildest form of holoprosencephaly is the solitary incisor. In the case described, the girl had only high palate and torus palatinus, but no other alteration in the midline. One of her brothers had cleft lip and palate, which indicates genetical determination. The girl has been orthodontically treated. PMID- 8005317 TI - [Experience with Otten's maxillomandibular fixation method]. AB - The authors are reporting on a method of mandibulomaxillary fixation worked out in their institute through a modification of those defined in literature. A wire hook is fixed by a screw to the mandibula and maxilla and, by the help of it an intermaxillary fixation is formed. The procedure is simple, quickly accomplishable and cheap. Its application is recommended to be introduced for other institutes, as well. PMID- 8005318 TI - [Tooth extraction under ether anesthesia in 1847]. AB - The newspaper "Ungar" edited in Pest, publishes a satirical drawing in 1847. This publication proves, that aether-narcosis--first employed in North-America autumn 1846--was known in spring 1847 already in Hungary too. PMID- 8005319 TI - [Periodontal status of institutionalized mentally retarded patients]. AB - The periodontal (PI) and the oral hygiene (OHI-S) indexes of 109 institutionalised mentally handicapped children were compared to PI and OHI-S indexes of 94 institutionalised healthy children. Both indexes showed significantly higher values at the handicapped group. Sex differences manifested only in the control group to the advantage of females. PMID- 8005320 TI - [Contact allergy reactions to Silodent impression material]. AB - The silicon based impression materials are often used in dental practice. Recently, we have observed two cases of contact allergic reaction after using Silodent (Ferrokemia) impression material. Epicutaneous test has shown that the allergic reaction is provoked by the catalisator. This hypersensitivity reaction is due to a previous sensibilization (e.g. previous impression taking or environmental hazards). No epicutaneous reaction to the other types of silicon based impression materials was found. PMID- 8005321 TI - [Correlation between meteorologic factors and periostitis of dental origin in Debrecen]. AB - Correlation between bioclimatical and meteorological factors is well documented. The aim of this study was to investigate the correlation between dental periostitis and meteorological fronts, cyclon and anticyclon. We found a positive, statistically significant correlation between occurrence of warm meteorological front, cyclon, anticyclon and prevalence of dental periostitis. It could have important implications in organizing the work of dental teams. PMID- 8005322 TI - School health nurses can make a difference. PMID- 8005323 TI - AHCPR announces two new guidelines. Clinical practice guidelines on the evaluation and management of early HIV infection. PMID- 8005324 TI - Pregnant teenagers' self reported reasons for seeking or not seeking prenatal care. PMID- 8005325 TI - A community benefit plan. PMID- 8005326 TI - Nurses involvement in public health safety issues. PMID- 8005328 TI - Neighborhood resource team "the nursing program specialist". PMID- 8005329 TI - School health service: "a pledge to the next generation". PMID- 8005327 TI - Update on Healthy Start in Palm Beach. PMID- 8005330 TI - Balancing the demands in your life through humor. PMID- 8005332 TI - NCLEX-RN CAT: a simulation for nursing students. PMID- 8005331 TI - Communicating across cultures: understanding the client who speaks a different language. PMID- 8005333 TI - Enabling career mobility in nursing: LPN to ADN articulation. PMID- 8005334 TI - Thinking about returning to school? Decision-making for RN-BSN education! PMID- 8005335 TI - Putting military training into civilian action. PMID- 8005336 TI - Reserve navy nurses save CHAMPUS thousands. PMID- 8005337 TI - What do we know about the timing of fertility transitions in Europe? AB - The Princeton project on the decline of fertility in Europe (the European Fertility Project) suggested that this historical fertility transition occurred virtually simultaneously in a wide variety of economic and social environments. This finding has been cited widely as evidence for an innovation/diffusion view of fertility transitions. We demonstrate that the demographic methods used to date the fertility transition in Europe--primarily Ig, and (to a lesser extent) the Coale-Trussell M&m indices--may fail to detect the initial stages of a fertility transition and therefore cannot be used as the basis for strong statements about the timing of transitions. We review these measurement problems and their implications for the current understanding of the European fertility transition. PMID- 8005338 TI - The validity of survey responses on abortion: evidence from Estonia. AB - This paper presents results of a validation survey of abortion conducted in Tallinn, Estonia in April and May 1992. The sample was drawn from patient records in a maternity hospital. Women who had an abortion in that hospital in 1991 were asked about recent abortions as part of a survey about women's health. More than 80% of the respondents reported having a recent abortion. Some respondents misreported their abortion as a miscarriage. Moreover, some variation in reporting was associated with respondents' characteristics. Ethnic Estonians were less likely to report their abortion than were Russians, women over age 40 were less likely to report the abortion than younger women, and women who had the abortion late in the first trimester were less likely to report that abortion. There was some evidence that unmarried women were less likely than married women to report their abortion, and that women who had borne three or more children were less likely to report their abortion than women who had borne fewer children. These differences probably stem from the extent to which pregnancy or abortion is considered stigmatizing for women in different situations. PMID- 8005339 TI - Migration and the Latino family: the union formation behavior of Puerto Rican women. AB - This study examines the transition to first union among Puerto Rican women. I argue that understanding the behavior of mainland Puerto Ricans requires attention to family patterns in Puerto Rico and to the dynamics of migration between Puerto Rico and the United States. The study therefore is based on pooled data from comparable surveys undertaken in the two settings. These data allow for event history analyses that compare the union formation behavior of migrants with that of nonmigrants, and consider the role of migration in producing the observed union patterns. Multivariate models show that migrants are more likely than nonmigrants to form unions early and to enter informal unions. Additional analyses show that selective migration plays a role in producing this pattern. Overall the findings demonstrate the importance of using data from both origin and destination locales for understanding the behavior of migrant groups. PMID- 8005340 TI - Changing mortality and morbidity rates and the health status and life expectancy of the older population. AB - This paper demonstrates the consequences of changes in mortality and health transition rates for changes in both health status life expectancy and the prevalence of health problems in the older population. A five-state multistate life table for the mid-1980s provides the baseline for estimating the effect of differing mortality and morbidity schedules. Results show that improving mortality alone implies increases in both the years and the proportion of dependent life; improving morbidity alone reduces both the years and the proportion of dependent life. Improving mortality alone leads to a higher prevalence of dependent individuals in the life table population; improving morbidity alone leads to a lower percentage of individuals with problems in functioning. PMID- 8005341 TI - Household registration type and compliance with the "one child" policy in China, 1979-1988. AB - This research analyzes how type of household registration, which reflects the degree of government control, affects compliance with China's "one child" policy for women at risk during the first decade of implementation. Although socioeconomic and cultural factors have significant effects on four fertility events after first live birth, household registration type is the most important. Furthermore, household registration type interacts with urbanization in such a way that the modernization influence associated with urbanization is more evident for women under less government control. The notable success of China's family planning program is linked to its unique system of government control. PMID- 8005342 TI - How economic development and family planning programs combined to reduce Indonesian fertility. AB - This paper examines the contributions of family planning programs, economic development, and women's status to Indonesian fertility decline from 1982 to 1987. Methodologically we unify seemingly conflicting demographic and economic frameworks into a single "structural" proximate-cause model as well as controlling statistically for the targeted (nonrandom) placement of family planning program inputs. The results are consistent with both frameworks: 75% of the fertility decline resulted from increased contraceptive use, but was induced primarily through economic development and improved education and economic opportunities for females. Even so, the dramatic impact of the changes in demand side factors (education and economic development) on contraceptive use was possible only because there already existed a highly responsive contraceptive supply delivery system. PMID- 8005343 TI - Family influences on family size preferences. AB - Several studies have demonstrated important effects of parents' childbearing behavior on their children's childbearing preferences and behavior. The study described here advances our understanding of these family influences by expanding the theoretical model to include parental preferences, siblings' behavior, and changes in children's preferences through early adulthood. Using intergenerational panel data from mothers and their children, we test the effects of both mothers' preferences for their own fertility and mothers' preferences for their children's fertility. Although both types of maternal preferences influence children's childbearing preferences, mothers' preferences for their children's behavior have the stronger and more proximate effects. Mothers' preferences continue to influence their children's preferences through early adulthood; siblings' fertility is an additional determinant of children's family size preferences. PMID- 8005344 TI - Linked lives, dependent demise? Survival analysis of husbands and wives. AB - Past research has found that married individuals have substantially lower risks of mortality than their single counterparts. This paper examines how household characteristics affect spouses' risks of mortality. A paired hazard rate model is estimated and tests are made to ascertain whether the estimated coefficients associated with risk factors differ between husbands' and wives' equations. Cigarette smoking, risk-avoidance behavior, poverty, and children are found to affect wives' and husbands' mortality in similar ways. Divorce, which can be interpreted as the termination of this shared household environment, is found to affect spouses differently. PMID- 8005346 TI - Ependymins and their potential role in neuroplasticity and regeneration: calcium binding meningeal glycoproteins of the cerebrospinal fluid and extracellular matrix. AB - 1. Ependymins are unique, highly divergent secretory proteins of the fish endomeninx. Thus far, no homologous sequences have been characterized in mammals. 2. Soluble ependymins are the predominant constituents of the cerebrospinal fluid of many teleost fish. A bound form of these glycoproteins is associated with the extracellular matrix probably with collagen fibrils. The latter may be the functional form of ependymins. 3. Ependymins bind Ca2+ via N-linked sialic acid residues leading to a conformational transition. 4. The molecular function of ependymins seems to be related to cell contact phenomena involving the extracellular matrix. For example, adhesive or anti-adhesive interactions may possibly influence ingrowing axons. PMID- 8005345 TI - Living arrangements of older Malaysians: who coresides with their adult children? AB - More than two-thirds of Malaysians age 60 or older coreside with an adult child. Data from the Senior sample of the Second Malaysian Family Life Survey (MFLS-2) are used to investigate which "seniors" (persons age 60 or older) live in this way. The analysis generally supports the notion that coresidence is influenced by the benefits, costs, opportunities, and preferences for coresidence versus separate living arrangements. For example, married seniors are more likely to coreside with adult children when housing costs are greater in their area or when the husband or wife is in poor health. This finding suggests that married parents and children live together to economize on living costs or to receive help with household services. Unmarried seniors who are better off economically are less likely to live with adult children, presumably because they use their higher incomes to "purchase privacy." PMID- 8005348 TI - Binding of meso-tetra(4-sulfonatophenyl)porphine to haemopexin and albumin studied by spectroscopy methods. AB - 1. The interaction of haemopexin and albumin with TPPS4 was studied by measuring the absorption and fluorescence spectra. Haemopexin was found to have one strong TPPS4 binding center (Ka = 3 x 10(7) M-1). 2. Haem-haemopexin complex appears to have no specific binding site for TPPS4. Occupation of the specific binding center of haemopexin molecule by a haem abolishes TPPS4 binding. 3. Albumin was found to possess one strong TPPS4 binding center (Ka = 3 x 10(6) M-1) besides two or three weak binding sites (Ka = 2 x 10(5) M-1). 4. Haem-albumin complex possesses only one weak TPPS4 binding site (Ka = 7 x 10(5) M-1). These observations suggest identity of primary binding sites of TPPS4 and haem on albumin molecule. PMID- 8005347 TI - Antiviral drugs: present status and future prospects. AB - 1. There is a limited number of antiviral drugs available for therapy. Many investigations and new analytical techniques have unraveled the development and progression of a viral infection. Nowadays there is a good understanding of the multiplication cycle of viruses, including the human immunodeficiency virus. 2. In this article the currently available antiviral drugs are presented arranged by their mode of action that can be understood by the multiplication cycle of the virus. 3. Clinical use and side-effects are discussed as well as place in current therapy. Some attention is paid on promising investigational antivirals. PMID- 8005349 TI - Prostaglandin E2/parathyroid hormone-induced suppression of alkaline phosphatase activity is mediated by protein kinase C. AB - 1. Bone resorptive factors, prostaglandin E2 and parathyroid hormone are shown to suppress alkaline phosphatase activity in a rat osteoblastic cell line. 2. Phorbol myristate acetate, but not dibutyryl cAMP or calcium ionophore can suppress alkaline phosphatase activity. 3. The protein kinase C inhibitors (H89, staurosporine) are able to block the suppression of alkaline phosphatase activity induced by prostaglandin E2 and parathyroid hormone. 4. These data suggest that protein kinase C is involved in the inhibition of alkaline phosphatase activity induced by prostaglandin E2 and parathyroid hormone. PMID- 8005350 TI - Kinetics of manganese reconstitution and thiol group exposition in dialyzed rat mammary gland arginase. AB - 1. Rat mammary gland arginase is a metallo-enzyme dependent on Mn2+, which can be only partially substituted by Cd2+. 2. Reconstitution of the activity of dialyzed arginase by manganese is a two-phase process; the second phase is independent of the cation concentration, with a half-time recovery (t1/2) of 10.77 min. 3. The apparent Km for Mn2+ is 280 microM and 10.5 microM for enzyme dialyzed for 24 and 72 hr, respectively. 4. Treatment with 5 mM EDTA at pH 6 totally inhibits enzyme activity, which is reconstituted by Mn2+. 5. Results obtained with iodoacetamide treatment suggest the existence of sulphydryl groups accessible only when the enzyme is dialyzed. PMID- 8005351 TI - Thrombin induces S-D-lactoylglutathione accumulation by enhancing platelet glycolytic pathway. AB - 1. Thrombin addition to human platelets stimulates L(+)lactate formation and S-D lactoylglutathione (SDL) accumulation. 2. Monoiodoacetamide decreases lactate formation and potentiates SDL accumulation through a significant increase of dihydroxyacetone phosphate and fructose1,6bisphosphate intracellular levels both in resting and in activated platelets. 3. A similar effect is produced by exogenous methylglyoxal on L(+)lactate formation and SDL accumulation. 4. Resting platelets completely transform (1 hr at 37 degrees C) the ketoaldehyde into D( )lactate: 5. When platelets are incubated in the presence of thrombin only 60% of the ketoaldehyde is found as D(-)lactate and the accumulated S-D lactoylglutathione represents about the 0.7% of the initial substrate. 6. During platelet stimulation with thrombin the hemithioacetal adduct, formed as a by product of glycolytic pathway, can be rapidly removed for important steps of cellular activation. PMID- 8005352 TI - Purification and characterization of casein kinase II from lactating rabbit mammary gland. AB - 1. Highly purified 200 kDa casein kinase II from rabbit lactating mammary gland (MG-CK II) was obtained by means of a new purification procedure consisting of one phosphocellulose and three Mono Q steps. 2. Its Km for ATP was 2.22 microM and 0.57 mg/ml and 0.13 mg/ml for partially dephosphorylated casein and phosvitin respectively. Stathmine was also suitable as substrate. 2-aminopurine and 6 dimethylaminopurine inhibited efficiently MG-CK II (Ki = 5 and 1 mM respectively). 3. MG-CK II autophosphorylated on its alpha-, alpha'- and beta subunits. The beta-subunit autophosphorylation was enhanced in presence of exogenous substrate. Its modulation was highly dependent on ATP concentration. 4. The effects of basic compounds which affected dramatically the phosphorylation of dephosphorylated casein in presence of various ATP concentrations were reported. PMID- 8005354 TI - Generation of C3- and C2-deuterated L-lactic acid by human erythrocytes exposed to D-[1-13C]glucose, D-[2-13C]glucose and D-[6-13C]glucose in the presence of D2O. AB - 1. The generation of C2- and C3-deuterated L-lactate was monitored by 13C NMR in human erythrocytes exposed to D-[1-13C]glucose, D-[2-13C]glucose or D-[6 13C]glucose and incubated in a medium prepared in D2O. 2. The results suggested that the deuteration of the C1 of D-fructose 6-phosphate in the phosphoglucoisomerase reaction, the deuteration of the C1 of D-glyceraldehyde-3 phosphate in the sequence of reactions catalyzed by triose phosphate isomerase and aldolase and the deuteration of the C3 of pyruvate in the reaction catalyzed by pyruvate kinase were all lower than expected from equilibration with D2O. 3. Moreover, about 40% of the molecules of pyruvate generated by glycolysis apparently underwent deuteration on their C3 during interconversion of the 2-keto acid and L-alanine in the reaction catalyzed by glutamate-pyruvate transaminase. 4. The occurrence of the latter process was also documented in cells exposed to exogenous [3-13C]pyruvate. 5. This methodological approach is proposed to provide a new tool to assess in intact cells the extent of back-and-forth interconversion of selected metabolic intermediates. PMID- 8005353 TI - Cetaben is an exceptional type of peroxisome proliferator. AB - 1. Cetaben in contrast to fibrates affect differently peroxisomal constituents. 2. Changes in large scale of liver non-peroxisomal parameters were compared after 10 days administration of equal doses (200 mg/kg/day) of cetaben and clofibric acid to male Wistar rats. 3. Clofibric acid treatment increased markedly the activities of FAD-glycerol-3-P dehydrogenase, beta-hydroxyacyl-CoA dehydrogenase, cytochrome-c oxidase, malic enzyme, NAD-glycerol-3-P dehydrogenase, ethoxycoumarin deethylase, p-nitroanisole demethylase and amounts of cytochrome P 450 and b5. 4. However no analogical changes were observed after cetaben treatment in the livers of experimental animals. 5. Both drugs increased the activities of alanine-glyoxylate aminotransferase-1 and acetylcarnitine transferase--enzymes with proven mitochondrial and peroxisomal location. 6. Cetaben contrary to clofibric acid does not increase solubilization of peroxisomal enzymes. 7. Enhanced acetylcarnitine transferase and alanine glyoxylate aminotransferase-1 activities were distributed in mitochondria as well as in peroxisomes after clofibric acid treatment, however, only peroxisomes were enriched after cetaben administration. 8. The results obtained suggest that cetaben represents an exceptional type of peroxisome proliferator, specifically affecting peroxisomes, without having a negative influence on the processes of peroxisome biogenesis. PMID- 8005355 TI - Evidence that the 5' end of rabbit globin mRNA is hybridized with its 3' end. AB - 1. A radiopolyadenylated rabbit globin mRNA was treated with different concentrations of ribonuclease V1 from cobra venom. 2. The enzymatic digests were chromatographed on an aminophenylboronate-agarose column, which specifically captured the cap structure i.e. m7G(5') ppp (5') NmP. 3. When the capture fragment was chromatographed on a Sephadex G-100 column, its size was smaller than the native molecule and also bore radioactivity, i.e. a poly(A) tail. 4. These results provide evidence that the 5' end (which encompasses the cap structure) of rabbit globin mRNA is hybridized and in close proximity to its 3' end. 5. We conclude that this conformation is required for messenger translation efficiency. PMID- 8005356 TI - Carnitine and derivatives in the central nervous system of chick embryo. AB - 1. Carnitine contents and the activity of carnitine acetyltransferase in the egg, in the embryo, and in different brain areas of central nervous system in chick embryo were determined in the course of development. 2. The egg showed low levels of free carnitine and acetylcarnitine. 3. In the whole embryo, at first stages of development, long chain acylcarnitine and acetylcarnitine were the best represented classes of carnitines. 4. In the brain regions acetylcarnitine levels, high at the first days, showed a continual decrease during development. 5. The activity of carnitine acetyltransferase increased and was totally related to development. PMID- 8005357 TI - The relationship between the trimethylation of lysine 77 and cytochrome c metabolism in Saccharomyces cerevisiae. AB - 1. Site directed mutations were constructed in the yeast iso-1-cytochrome c gene adjacent to the lysine 77 (methylation site) codon. 2. These mutant genes were then cloned and transformed into the S. cerevisiae strain B-6642 which contains a deficiency in the iso-1-cytochrome c gene. 3. The resulting transformants were screened for cytochrome c production using gel electrophoresis. 4. Amino acid analysis of the mutated cytochromes c demonstrated varying levels of trimethyllysine formation, depending on the nature of the site directed mutation. 5. The resulting transformants were then used as tools in order to investigate the relationship between trimethyllysine formation and various aspects of cytochrome c metabolism including protein stability and heme conjugation. PMID- 8005360 TI - Assessment of risk factors for pneumonia in dysphagic children: significance of videofluoroscopic swallowing evaluation. AB - The purpose of this study was to investigate the relationship between aspiration, as identified by videofluoroscopic swallowing (VFS) study, and pneumonia in children with suspected dysphagia. Data were retrospectively collected and analysed from 142 children referred for VFS over a one-year period. The median age was 33 months. Aspiration was identified in 44 per cent of the children studied. A history of pneumonia within one year of the VFS was found in 35 per cent. Aspiration, gastro-oesophageal reflux, and age one year or less were significant risk factors for pneumonia. Children with traumatic brain-injury were at less risk for pneumonia than all other children with suspected dysphagia. These results lend objective support to the previously suspected relationship between aspiration and pneumonia in this patient population. PMID- 8005358 TI - Bilateral spastic cerebral palsy--a comparative study between southwest Germany and western Sweden. II: Epidemiology. AB - Epidemiological data of a collaborative study on children with bilateral spastic cerebral palsy (BSCP) between south-west Germany and western Sweden are reported. The study period covered the birth years 1975 to 1986. Overall, the rate of BSCP increased during the birth year periods 1975-77 and 1978-80, but decreased thereafter. The rise was due to an increase of BSCP in low-birthweight (LBW) children, especially very LBW (VLBW) children. Mortality rates in LBW, and particularly VLBW, children decreased significantly during the whole study period in both countries. The BSCP rate, after the initial increase, showed a decrease during the second half of the study period in LBW children. Results are interpreted in favour of a predominantly prenatal aetiology in normal-birthweight and of a predominantly peri- and neonatal aetiology in LBW children. PMID- 8005359 TI - Temporomandibular joint contracture in spastic quadriplegia: effect on oral-motor skills. AB - This study assessed the temporomandibular joint of 34 children with spastic quadriplegic cerebral palsy for contractures to determine whether joint abnormalities were related to oral-motor dysfunction. Subjects were found to have restrictions in mandibular range of motion, increased overjet and decreased overbite. Increased overjet corresponds to retrognathia and decreased overbite relates to fixed posterior rotation of the mandible. The severity of many of these abnormalities correlated with the severity of oral-motor dysfunction. Abnormalities in overbite were particularly significant. The authors conclude that temporomandibular joint contractures in this population are related to problems in oral-motor function. It is hoped that further research in this area will lead to new therapies for children with feeding and swallowing problems. PMID- 8005361 TI - Verbal and non-verbal function of children with right- versus left-hemiplegic cerebral palsy of pre- and perinatal origin. AB - Eighteen children with right- and 13 with left-sided congenital hemiplegia were compared with 19 normal age-matched controls for verbal and non-verbal function. CT scans were obtained from 27 of the 31 hemiplegic children. The two hemiplegic groups were impaired in non-verbal function compared with controls. The right hemiplegic group was more impaired in verbal function than the left-hemiplegic group and controls; however, impairments were restricted to the girls in the right-hemiplegic group. The results are discussed in terms of cerebral plasticity and functional reorganisation of cognitive functions after an early unilateral injury. It is argued that girls with left-hemisphere lesions may be more limited in cerebral plasticity than boys. PMID- 8005362 TI - Anatomy of diplegia: an hypothesis. AB - Periventricular leukomalacia (PVL) occurring in relation to the body of the lateral ventricle could account for damage to the corticospinal tracts. However, PVL in this location is relatively rare, and the view that it causes the diplegia of preterm birth is challenged on the anatomical grounds that the corticospinal tracts to the legs are some distance away from the main sites of PVL, which are at the collateral trigone and near to the interventricular foramen. If PVL lesions do cause permanent nerve damage, it is surprising that cortical blindness in diplegia is so uncommon. A dying-back neuropathy caused by selective damage to corticospinal neurons could be considered as an alternative hypothesis to account for the paralysis of diplegia. PMID- 8005363 TI - Treatment of faecal incontinence in a child with sacral agenesis: the use of biofeedback training. AB - The case of a 14-year-old girl is presented who was born with sacral agenesis and severe, chronic constipation not responding to laxative treatment. Biofeedback was employed in the treatment of the constipation and soiling. After six treatment sessions over four months, the constipation and soiling ceased and there was no relapse during follow-up of 12 months. Although this child had an absence of S3-S5 and the coccyx, with possible innervation abnormalities, this case illustrates that biofeedback training might be a useful adjunct to existing therapies. PMID- 8005364 TI - Skeletal maturity in myelodysplasia. AB - Incongruent skeletal age in 76 myelomeningocele patients was assessed by a single hand and wrist bone-age film. 28 per cent of patients were found to have a bone age of more than two standard deviations from their chronological age. 22 per cent had advanced skeletal age. Below eight years of age, only 11 per cent were advanced, but over this age 32 per cent showed skeletal maturity exceeding chronological age. Gender, neurological level, presence of hydrocephalus and number of shunt revisions did not correlate with the prevalence of advanced bone age. PMID- 8005365 TI - Head circumference and IQ of children with sex chromosome abnormalities. AB - At all ages XXX girls had significantly smaller head circumferences than control girls. Their IQ deficit was 24 points and IQ at age seven correlated significantly with head circumference at birth. In XXY boys, head circumference was significantly reduced at birth and up to nine years of age. The XXY boys' IQ deficit was 22 points, but IQ did not correlate with head circumference, as reductions in the two parameters did not always occur in tandem. The ratio of height-to-head circumference differed most in this group and could be useful in clinical recognition of this condition. XYY boys' head size did not differ from controls, despite their greater height, lower IQ scores indicating an adverse effect of an additional Y chromosome on brain development. The major factor affecting IQ outcome in the cohort was abnormal karyotype, with smaller effects from social class and head growth. PMID- 8005366 TI - Cranial auscultation in two children with intracranial vascular malformation. AB - Although most bruits heard over the skull in children are innocent, they might represent the sign of a treatable intracranial vascular pathology. Nevertheless, cranial auscultation is not routinely carried out during physical examination at a young age. Two children with vascular malformations are described in whom a cranial murmur was an early sign of intracranial vascular pathology. Routine cranial auscultation during physical examination of children is recommended. PMID- 8005367 TI - Congenital peripheral neuropathy presenting as apnoea and respiratory insufficiency. AB - A seven-week-old girl presented with recurrent apnoeic episodes and respiratory insufficiency. The child was hypotonic, weak, areflexic and had a paradoxical movement of the right hemidiaphragm. Cranial nerve and sphincter function was normal; there was no fasciculation. Nerve conduction studies showed a severe axonal sensory and motor peripheral neuropathy. Biopsy of the sural nerve revealed marked axonal atrophy. The infant is now over two years of age, is ventilator-dependent and has clinical and electrophysiological evidence of further progression of one of the earliest reported presentations of a congenital peripheral neuropathy. PMID- 8005368 TI - Kleine-Levin syndrome. PMID- 8005369 TI - The interactive toxicity of CHCl3 and BrCCl3 in precision-cut rat liver slices. AB - The interactive toxicity of two nontoxic concentrations of chloroform (CHCl3) and bromotrichloromethane (BrCCl3) was examined in precision-cut rat liver slices. Liver slices were prepared from male Sprague-Dawley rats (220-250 g) pretreated with phenobarbital for 4 days. Toxicants were administered 1 hr apart. Intracellular K+ levels were similar to untreated controls in slices treated with 0.2 mM CHCl3 or 0.125 microliters (0.25 mg, 1.26 mumol) BrCCl3 alone, indicating that these concentrations were nontoxic. However, addition of both toxicants, irrespective of order, resulted in a time-dependent loss of intracellular K+ which was significant at 9 hr following administration. This was interpreted as evidence of synergistic toxicity. Cytochrome P450 loss was significant as early as 3 hr following exposure to BrCCl3, alone or when added with CHCl3. This loss may be attributed to BrCCl3-induced suicide inactivation of cytochrome P450. Centrilobular hepatocytes may be more susceptible to the interactive toxicity of CHCl3 and BrCCl3. Activity of enzymes found predominantly in this area was significantly decreased in slices exposed to both toxicants relative to controls. Conversely, activity of enzymes found predominantly in the periportal region was similar to that of untreated and treated controls. Interactive toxicity of BrCCl3 and CHCl3 was not a consequence of increased lipid peroxidation or depletion of slice glutathione content. Further studies need to be conducted to elucidate the mechanisms mediating the interactive toxicity of BrCCl3 and CHCl3. PMID- 8005370 TI - Air samples from a building with asbestos-containing material: asbestos content and in vitro toxicity on rat pleural mesothelial cells. AB - Buildings equipped with asbestos-containing material may release asbestos fibers, the toxicity of which remains uncertain because of the generally low dose level. In 22 air samples collected in a building the asbestos level ranged between 0 and 0.027 f/ml. Both chrysotile and amphiboles were found. There was no association between in vitro cytotoxicity on rat pleural mesothelial cells and asbestos content, but there was a significant correlation with the total amount of particulate material. Four samples exhibited an enhancement of DNA synthesis in cells arrested in G1 with 5 mM hydroxyurea. This is more likely related to the particulate matter associated with asbestos fibers. PMID- 8005371 TI - Acute, subacute, and subchronic inhalation toxicity studies of respirable polymeric methylene diphenyl diisocyanate (polymeric MDI) aerosol in rats. AB - Short-term inhalation toxicity studies with respirable polymeric methylene diphenyl diisocyanate (polymeric MDI) aerosol were performed in rats. The 4-hr LC50 was found to be 490 mg polymeric MDI/m3 (95.5% < 4.3 microns). Exposure of (4-week-old) rats to 0, 2.2, 4.9, or 13.6 mg polymeric MDI/m3 (95% < 5 microns) for 2 weeks resulted in mortality, severe growth retardation, and elevated lung weights at 13.6 mg/m3; at 4.9 mg/m3 slight growth retardation and slightly elevated lung weights were observed. A 13-week study with 6-week-old rats exposed to 0.35, 1.4, or 7.2 mg polymeric MDI/m3 (95% < 5 microns) revealed transient growth retardation and a slightly increased number of pulmonary alveolar macrophages occasionally accompanied by increased numbers of mononuclear cells and fibroblasts in alveolar septa only at 7.2 mg/m3. In a second 2-week study with 4- or 6-week-old rats exposed to 14.1 mg polymeric MDI/m3 (95% < 5 microns), 4-week-old rats died earlier and in greater numbers than 6-week-old rats. In a second 13-week study with 6-week-old rats, using exposure concentrations of 0, 4.1, 8.4, and 12.3 mg polymeric MDI/m3 (95% < 5 microns) and including a 4-week recovery period, 12.3 mg/m3 induced mortality, growth retardation, severe respiratory distress, increased lung weights, degeneration and hyperplasia of the nasal epithelium, accumulations of macrophages in the lungs and mediastinal lymph nodes, and focal inflammatory changes in the lungs.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8005372 TI - Chronic inhalation toxicity and carcinogenicity study of respirable polymeric methylene diphenyl diisocyanate (polymeric MDI) aerosol in rats. AB - Four groups of 60 Wistar rats of each sex were exposed by inhalation to 0, 0.2, 1.0, or 6.0 mg/m3 respirable polymeric methylene diphenyl diisocyanate (polymeric MDI) aerosol (93.5% < 4.2 microns) for 6 hr a day, 5 days a week for up to 24 months. In addition, satellite groups of 10 rats/sex/group received the same treatment for 12 months. There was no adverse effect on general health, survival, body weight, or hematological or clinical chemistry parameters. Lung weights were increased in both males and females exposed to 6.0 mg polymeric MDI/m3 for 12 or 24 months. Gross examination at autopsy of males exposed to 6.0 mg polymeric MDI/m3 for 24 months revealed an increased incidence of spotted and discolored lungs. Increased incidences of degeneration and basal cell hyperplasia of the nasal olfactory epithelium, often accompanied by hyperplasia of Bowman's glands, were found in the 1.0 and 6.0 mg/m3 groups. Light and electron microscopic studies of the lungs revealed accumulations of alveolar macrophages containing polymeric MDI-associated refractile yellowish material at the level of the alveolar duct in all exposed groups. Alveolar duct epithelialization as well as fibrosis of tissues surrounding the macrophage accumulations occurred at the 1.0 and 6.0 mg/m3 exposure levels. In addition, increased incidences of calcareous deposits and localized alveolar bronchiolization were seen in the 6.0 mg/m3 group. Moreover, eight pulmonary adenomas (six in males and two in females) and one pulmonary adenocarcinoma (in a male) were observed in the 6.0 mg/m3 exposure group. The time sequence of the spectrum of pulmonary changes indicates that recurrent alveolar wall damage by polymeric MDI and/or polymeric MDI-containing alveolar macrophages leads to alveolar bronchiolization and ultimately to bronchioloalveolar tumors. No lung tumors were found in the lower concentration groups and in the control group. The incidence and distribution of other types of tumors were not influenced by polymeric MDI. It was concluded that in the present study, the "no-observed-adverse-effect level" of polymeric MDI was 0.2 mg/m3, and that chronic exposure to polymeric MDI at a level of 6.0 mg/m3 was related to the occurrence of pulmonary tumors. It was also concluded that exposure to polymeric MDI at concentrations not leading to recurrent lung tissue damage will not produce pulmonary tumors. PMID- 8005374 TI - Subchronic oral toxicity study of diisopropyl methylphosphonate in mink. AB - Diisopropyl methylphosphonate (DIMP), produced during manufacture of the chemical agent GB (Sarin), is a groundwater contaminant at Rocky Mountain Arsenal, Colorado. DIMP was fed for 90 days to dark brown "Ranch Wild" mink housed under controlled indoor conditions. One-year-old mink, 10 of each sex, were fed 0, 50, 450, 2700, 5400, or 8000 ppm in standard ranch diet. Actual DIMP consumption was 0, 8, 73, 400, 827, and 1136 mg/kg body wt/day, respectively. Two additional groups of 10 served as "pair-fed" controls. Body weight and food intake were recorded weekly. Complete blood count and 15 chemical analytes were measured at Weeks 0, 3, 7, and 13. Necropsy and microscopic examination were performed on all mink. No clinical morbidity or deaths occurred. Both sexes fed 8000 ppm ate approximately 20% less and weighed approximately 20% less than the controls; 5400 ppm females had a 10% weight decrement. Plasma cholinesterase (ChE) decreased in the top three dose groups starting at Week 3. At 13 weeks, decrements were approximately 50% but returned to normal after 1 week without DIMP. Erythrocyte ChE was not reduced. Heinz bodies occurred in 10-15% of RBCs in 50% of 8000 ppm mink at 13 weeks, and 0.1-2.0% of RBCs in 25% at 2700 ppm. There were mild decreases in RBC count, hematocrit, and hemoglobin, and increases in reticulocyte count, at the 5400 and 8000 ppm doses. All recovered within 3 weeks after DIMP was withdrawn. The 8000 ppm group had marginal splenic hematopoiesis, histologically. No other treatment-related changes were noted. The 450 ppm dose was a clear no-effect level (approximately 73 mg DIMP/kg body wt/day). Compared to reports of similar studies of DIMP in rats and dogs, these mink displayed no unique species susceptibility. PMID- 8005373 TI - Leydig cell hyperplasia and adenomas in mice treated with finasteride, a 5 alpha reductase inhibitor: a possible mechanism. AB - Finasteride is a selective inhibitor of the enzyme 5 alpha-reductase which is responsible for the conversion of testosterone (T) to dihydrotestosterone (DHT). Finasteride is indicated for the treatment of benign prostatic hyperplasia in man (approximately 0.1 mg/kg/day). The effect of long-term treatment was studied in mice given high doses (2.5, 25, and 250 mg/kg/day) of finasteride for 83 weeks. In finasteride-treated mice, increased incidences of testicular Leydig cell hyperplasia (52% compared to 24% in control group) at doses equal to or greater than 25 mg/kg/day and Leydig cell adenomas (32% compared to 0.5% in control group) at 250 mg/kg/day were observed. There were no drug-related effects on the seminiferous tubules. Since luteinizing hormone (LH) is a trophic hormone for Leydig cells, short-term studies (5 to 14 weeks) were done to investigate the relationship between Leydig cell hyperplasia and serum LH levels in finasteride treated mice. In these studies, there was a positive correlation between the drug related increased incidence of Leydig cell hyperplasia and a statistically significant (p < or = 0.05) increase in serum LH levels in finasteride-treated (250 mg/kg/day) mice. Furthermore, studies in castrated male mice showed that the suppression of serum LH levels by T is reversible by inhibition of conversion of T to DHT with finasteride (250 mg/kg/day), supporting the hypothesis that DHT is involved in the regulation of LH release in mice.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8005375 TI - Pulmonary toxicity to intratracheally administered indium trichloride in Fischer 344 rats. AB - The use of indium by the semiconductor industry has risen sharply in recent years with the discovery that the electrical properties of compounds such as indium phosphide and indium arsenide are better than those of silicon. However, relatively little is known about its potential to induce lung damage. These studies examined the effect of indium trichloride (InCl3) on the lung. To examine the disposition and removal of InCl3 from the lung, groups of female Fischer 344 rats received a single intratracheal dose of 1.3 mg In/kg as InCl3 and were euthanized after 1, 2, 4, 7, 14, 28, and 56 days at which time lung samples were analyzed for metal content. Furthermore, the histology, hydroxyproline levels, and bronchoalveolar lavage (BAL) fluid cellularity of the lung were studied. In addition, the effect of 0.00016, 0.00325, 0.065, and 1.3 mg In/kg on inflammatory response and BAL fluid cellularity was compared. While a dose as low as 0.00325 mg In/kg was capable of initiating an influx of inflammatory cells, instillation of 1.3 mg In/kg resulted in an inflammatory response that was still evident 56 days later. After 28 days, the lung weight of the InCl3-treated animals was 2.5 times greater than that of the controls. The total cell number in the BAL fluid of the treated animals after 28 days was 32 times higher than that in the control rats. Sixty-seven percent of these cells were granulocytes. Compared to the controls, the hydroxyproline content of the lungs from the InCl3-treated animals were two-fold greater after 28 and 56 days. Furthermore, the levels of fibronectin and TNF alpha present in the BAL fluid of InCl3-treated rats increased sharply during the first 24 hr and remained elevated 56 days later. These data and the histological examination of the lung following InCl3 treatment suggest that InCl3 is capable of causing severe lung damage and the development of fibrosis. PMID- 8005376 TI - A comparison of the acute behavioral effects of alkylbenzenes using a functional observational battery in mice. AB - The acute neurobehavioral effects of six alkylbenzenes (benzene, toluene, ethylbenzene, propylbenzene, m-xylene, and cumene) were evaluated after 20-min inhalation exposures using a functional observational battery (FOB) in mice. In order to do this, an explicit protocol for the FOB developed for rats by Moser was adapted for use in mice with inhalation exposures. All six alkylbenzenes, in the concentration range of 2000 to 8000 ppm, produced a nearly identical profile of effects, a profile that was also produced by ip administration of the central nervous system depressant drug pentobarbital. These effects included changes in posture, decreased arousal and rearing, increased ease of handling, disturbances of gait, mobility, and righting reflex, decreased forelimb grip strength, increased landing foot splay, and impaired psychomotor coordination. The response to various sensory stimuli was also decreased by the alkylbenzenes and pentobarbital. These acute effects of alkylbenzenes were short-lived, with recovery beginning within minutes of removal from the exposure chamber. The finding that the alkylbenzenes produce a profile of neurobehavioral effects similar to that of pentobarbital is consistent with a growing body of other evidence that many solvents produce a profile of acute effects similar to that of central nervous system depressant drugs and ethanol. PMID- 8005377 TI - Developmental toxicity and structure-activity relationships of aliphatic acids, including dose-response assessment of valproic acid in mice and rats. AB - The anticonvulsant valproic acid (VPA), or 2-propylpentanoic acid, is a short chain aliphatic acid that is teratogenic in humans and rodents. VPA and 14 related chemicals were screened for developmental toxicity using the Chernoff/Kavlock assay. Test agents, in corn oil, were administered by gavage to Sprague-Dawley rats once daily during organogenesis. The dams were allowed to deliver and the pups were examined postnatally. Segment II studies were also conducted using VPA and pentanoic acid in rats and with VPA in CD-1 mice. In both mice and rats, VPA caused transient maternal ataxia and developmental defects of the digits and, especially, the axial skeleton. Exencephaly, however, was seen only in mice. The screening protocol was effective in prioritizing agents within this class of compounds for more definitive developmental toxicity testing. All congeners tested induced maternal respiratory effects and six compounds caused motor depression. Only 2-ethylhexanoic (2EH) and 2-propylhexanoic (2PH) acid caused dramatic VPA-like effects on rat development (including mortality, extra presacral vertebrae, fused ribs, and delayed parturition), confirming the strict structural requirements for developmental toxicity previously reported for acute exposure in mice. The incorporation of skeletal examinations in the Chernoff/Kavlock assay enabled the detection of the sole developmental effect (increased incidence of lumbar ribs) of 2-butylhexanoic acid. VPA, 2EH, and 2PH were among the compounds that caused maternal motor depression. These data, consistent with previous reports, indicate a broader specificity for activity in the adult nervous system than that in the developing system and suggest differing mechanisms for the two effects. PMID- 8005378 TI - Quantitative whole body autoradiographic disposition of glycol ether in mice: effect of route of administration. AB - Glycol ethers such as ethylene glycol monomethyl ether (EGME) are common solvents used in many industrial products. A large number of individuals are exposed to EGME through different exposure routes. We investigated the differential distribution of EGME following various routes of administration using whole body autoradiographic (WBA) techniques. Male B6C3F1 mice were treated with tracer iv or oral doses of [2-14C]EGME (4.05 micrograms EGME/kg equivalent to 0.8 mCi/kg) and euthanized at 1 and 24 hr following treatment. In both groups of animals the highest levels of radioactivity were detected in the liver, urinary bladder, bone marrow, kidney, and epididymis, at 1- and 24-hr time periods. Computer-assisted quantitation of WBA indicated that there was markedly higher deposition of [2 14C]EGME and/or its metabolites in various tissues of the orally treated animals than in animals treated intravenously. Our studies also suggest that [2-14C]EGME is rapidly distributed either from blood or stomach to various tissues. Preferential deposition of radioactivity in the peripheral tissues of the bone, with a progressive inward accumulation in the bone marrow, was observed. Selective permeability of EGME and/or its metabolites was indicated by the higher uptake by the epididymis than that by testis. The high levels of radioactivity in biosynthetically active tissues, e.g., the liver, bone marrow, and gastric mucosa, is an indication of persistent interaction of the compound with cellular components of these tissues. These interactions may lead to EGME toxicity. PMID- 8005379 TI - A toxic equivalency factor scale for polychlorinated dibenzofurans. AB - The ethoxyresorufin O-deethylase (EROD) induction of 20 polychlorinated dibenzofurans (PCDFs) was examined in the H4IIE rat hepatoma cell bioassay. The selection of the compounds tested was based on a multivariate chemical characterization laying the groundwork for covering the whole chemical series of PCDFs. The EROD induction potency was found to vary in ED50 values from 25 to 100,000,000 pg/mg, i.e., nearly seven orders of magnitude. The response of the bioassay was calibrated against the 2,3,7,8-tetrachlorodibenzo-p-dioxin, enabling the corresponding toxic equivalency factors (TEFs) to be calculated. In order to establish a quantitative structure-activity relationship (QSAR) for the TEF values, 37 physicochemical descriptor variables were used to chemically characterize the 87 tetra- to octachlorinated PCDFs. Using partial least-squares modeling on a training set of 10 congeners, a QSAR model with sound predictive power was obtained. The QSAR model was validated with a validation set of additional 10 congeners. The predicted TEFs indicate that a large number of congeners are potent EROD inducers. PMID- 8005380 TI - Induction of chromosomal aberrations, cytotoxicity, and morphological transformation in mammalian cells by the antiparasitic drug flubendazole and the antineoplastic drug harringtonine. AB - The antiparasitic drug flubendazole and the antineoplastic compound harringtonine were studied for ability to induce chromosomal damage in Chinese hamster lung (CHL) cells and cytotoxicity and morphological transformation in C3H/10T1/2 Cl 8 (10T1/2) mouse embryo fibroblasts. Flubendazole caused a dose- and time-dependent induction of polyploidy in CHL cells. In cells treated with 0.78 micrograms/ml flubendazole, the yield of polyploid cells was 95%. Harringtonine caused a dose- and time-dependent induction of chromosome breaks, and 0.195 micrograms/ml harringtonine induced chromosome breaks in 47% of CHL cells. Both flubendazole and harringtonine caused dose-dependent cytotoxicity to 10T1/2 cells at concentration ranges of 0.04-1.60 and 0.05-0.8 micrograms/ml, respectively. Flubendazole and harringtonine at concentrations of 0.08-0.4 and 0.4-0.8 micrograms/ml, respectively, induced morphological transformation (predominantly type II foci) in 10T1/2 cells. Three of four harringtonine-transformed cell lines and two of four flubendazole-transformed cell lines formed foci in reconstruction experiments with non-transformed 10T1/2 cells. All four harringtonine-transformed and all four flubendazole-transformed cell lines formed colonies in soft agar. Similar concentrations of flubendazole and harringtonine induced chromosome damage in CHL cells and cytotoxicity and morphological transformation in 10T1/2 cells. The ability of flubendazole to induce polyploidy may be part of the mechanism by which this compound induces morphological transformation. Similarly, the ability of harringtonine to induce chromosomal aberrations may be part of the mechanism by which this compound induces morphological transformation. Therefore, flubendazole and harringtonine induce cytotoxicity and morphological and anchorage-independent transformation, harringtonine induces chromosome aberrations (breakage, translocation, and rings), and flubendazole induces polyploidy in cultured mammalian cells. The clastogenic and cell transformation inducing properties of these compounds suggest that these drugs may have carcinogenic potential. This should be investigated rigorously in animal carcinogenesis bioassays. The genotoxicity of these drugs should be considered during their development as antiparasitic and antineoplastic agents. PMID- 8005381 TI - Progressive serum IgE elevation in the B6C3F1 mouse following withdrawal of dietary vomitoxin (deoxynivalenol). AB - Vomitoxin (deoxynivalenol) is a fungal toxin that induces serum IgA hyperelevation, IgA autoantibodies, mesangial IgA deposition in mice upon dietary exposure. The capacity of dietary vomitoxin to similarly alter serum IgE was assessed in female B6C3F1 mice. Ingestion of 25 ppm vomitoxin in AIN-76A semipurified diet resulted in 2.7-, 4-, 5- and 2.3-fold increases in serum IgE relative to controls after 12, 16, 20, and 24 weeks of toxin feeding, respectively. When mice were fed 25 ppm vomitoxin for 8 weeks and continued on toxin-free diet, serum IgE levels were 2.4, 4, 4.9, and 2-fold that of controls at 12, 16, 20, and 24 weeks, respectively. IgE levels were not significantly different between treatment and withdrawal groups at Weeks 12-24. These results differed from those of serum IgA, which increased much earlier and only during toxin administration, and those of IgG, which was largely unaffected compared to controls. The results indicate that a defined period of vomitoxin ingestion can subsequently induce progressive dysregulation of IgE production in addition to previously described IgA-related pathologic effects. PMID- 8005382 TI - Indirect costs of research--beyond self-interest. PMID- 8005383 TI - Science, technology, and the federal government: comments on a recent NAS report. PMID- 8005384 TI - Introduction: optical microscopy in physiological investigations. PMID- 8005385 TI - Applications of ratio fluorescence microscopy in the study of cell physiology. AB - Quantitative fluorescence microscopy is becoming an increasingly important tool in the study of cell biology. Fluorescence microscopy has long been used for qualitative characterizations of subcellular distributions of proteins, lipids, nucleic acids, and ions, but quantifying these distributions is complicated by a variety of optical, biological, and physical factors. Many factors that complicate quantification of fluorescence in cells can be circumvented by analyzing fluorescence ratios derived from pairs of fluorescence images. In this review we will discuss the factors that affect fluorescence quantification, the advantages of quantifying fluorescence as a ratio, and give examples of how fluorescence ratio microscopy is being applied in studies of cell biology. PMID- 8005386 TI - Evolving concepts in molecular pathology. AB - During the last decade, an understanding of the causes of many human diseases has progressed rapidly, in large measure because of the development of technologies that allow us to identify the genes that are involved. Identification of a gene that is suspected to play an important role in a particular disease opens up a whole new dimension of research to understand the molecular events that underlie the cause of that disorder. A crucial step in this process is often the development of an animal model of the disease. Again, the last decade has seen rapid advances in our ability to create such models, particularly in mice. Technologies that allow for the addition, alteration, or elimination of individual genes from the genome to create a transgenic mouse are now routine. The advantages of having a transgenic mouse model of a human disease are many. These animals often provide the first unequivocal proof that a particular gene is responsible for causing the pathological changes that occur with disease. They also can provide a system to carefully dissect the successive events that lead to the disease state, and can provide a custom-designed whole animal system to test potential therapies to treat and eventually cure the disease. Most important, new concepts relating to gene expression and gene function in disease often emerge from such transgenic studies. This review will illustrate several examples in which transgenic animals have contributed significantly to the evolution of concepts of the underlying mechanisms of human disease. PMID- 8005387 TI - Cell surface down-modulation of CD4 after infection by HIV-1. AB - Entry of HIV-1 into host cells is generally mediated by the cell surface CD4 receptor after specific interaction with the viral envelope glycoprotein gp120. Infection by HIV-1 commonly leads to the disappearance of CD4 from the plasma membrane, a phenomenon referred to as receptor down-modulation. This, in turn, renders cells refractory to subsequent infection by the same or other viruses that use the CD4 receptor for entry, creating a state of superinfection immunity. CD4 down-modulation is a complex process involving a variety of viral gene products, the effects of which may be manifest at different stages within the viral replication cycle. CD4 disappearance from the cell surface occurs in each of the CD4+ lymphocytes, T-cell lines, monocytic cell lines, and monocyte-derived macrophages. Internalization of CD4 can occur after binding of either gp120 alone or gp120 antigen-antibody complexes, and may also be mediated by the HIV-1 Nef gene. Other factors that cause cell surface CD4 depletion include reductions in CD4 transcript levels, impaired translation of CD4 mRNA, formation of CD4-gp160 intracellular complexes, and degradation of CD4 mediated by the HIV-1 Vpu gene. PMID- 8005388 TI - T cell anergy. AB - T cell clonal anergy is a proposed mechanism of immunologic self tolerance in which T cells become functionally inactivated after previous stimulation. MHC class II-restricted antigen presentation by different cell types has been speculated to have a role in determining activation vs. anergy in responding T cells. Human T cells express MHC class II after activation and have been shown to present high concentrations of degraded peptide antigen to autologous T cells resulting in clonal anergy. In contrast to low antigen dose T cell clonal anergy, which occurs in the absence of costimulation, T cell anergy induced by human T cell presentation of antigen results in both primary proliferation and secondary unresponsiveness to high-dose antigenic stimulation. Although clonal anergy was previously thought to prevent autoreactive T cells from ever responding to self antigen presented without costimulation, we postulate that T cell presentation of antigen represents a "fail-safe" mechanism of immunologic self tolerance that would anergize clonally expanded autoreactive T cells when they are surrounded by a high extracellular concentration of degraded self antigen. PMID- 8005390 TI - Peptide secretion: what do we know? AB - Understanding factors that regulate peptide release became an issue when the presence and possible role of these compounds as transmitter/modulators in various systems were realized. Many studies measuring the levels of peptides in various tissues and fluids have been performed using radioimmunoassay. However, because these peptides are measured in postmortem tissues, or perfusates that are collected at time intervals that do not approach the time scale used for exocytosis, limited information can be derived from these data. Recently the quantitative use of Northern analysis, RNase protection assays, and in situ hybridization has led to a large literature reporting on changes in peptide mRNA levels as a consequence of a variety of treatments. The assumptions involved in using radioimmunoassay measurements of peptide levels and the various methods used to measure peptide mRNAs are different, but data obtained from experiments using both methods are nonetheless used as an indication of the regulation of peptidergic neurons, and ultimately of peptide release. The mechanisms dedicated to translating cellular input into alterations in secretion have begun to be appreciated at a molecular level. Herein we will discuss the cell biology of regulated secretion and consider some levels in this pathway at which peptide release may be controlled. PMID- 8005389 TI - Iron nutriture in elderly individuals. AB - The purpose of this review is to examine current research on the iron status of the elderly and factors that influence the body burden of iron. Studies of noninstitutionalized elderly individuals report mean iron intakes that meet current Recommended Dietary Allowances for iron. Dietary practices that may decrease iron bioavailability, and hence iron stores in the body, include low intakes of ascorbic acid or high intakes of calcium, and decreased consumption of highly available iron from meat, fish, and poultry. Although not well documented, the effect of age on iron absorption and iron excretion appears to be small, and body stores of iron increase with age. It is difficult to estimate the prevalence of iron deficiency in elderly persons, because impaired iron status can be the result of iron deficiency or chronic disease. Further study is necessary to determine whether red blood cell ferritin and serum transferrin receptors may be useful biochemical markers to differentiate the anemia of chronic disease from iron deficiency anemia. Hereditary hemochromatosis is a genetic disease that greatly increases the body burden of iron and the risk of hepatic disease among homozygotes. Because iron deficiency or iron excess may impair health, the role of iron in diseases associated with aging such as depressed immune response, neurological dysfunction, cancer, and heart disease is discussed. PMID- 8005391 TI - Bcl-2 inhibits glucocorticoid-induced apoptosis but only partially blocks calcium ionophore or cycloheximide-regulated apoptosis in S49 cells. AB - Many non-Hodgkins B-cell lymphomas possess a deregulated bcl-2 gene resulting in a phenotype that is apparently resistant to programmed cell death (apoptosis). We have used a mouse lymphoma cell line (S49.1) that undergoes apoptosis in response to a variety of stimuli to determine the effect of bcl-2 expression on induction of apoptosis. S49 cells were stably transfected with recombinant amphotrophic retroviruses carrying either a G418 antibiotic resistance gene alone (S49-NEO) or this gene in combination with a bcl-2 complementary DNA (S49-Bcl-2). Three different agents previously shown to activate apoptosis by different pathways in S49 cells (dexamethasone, the calcium ionophore A23187, and cycloheximide) were used to examine the effect of bcl-2 expression on cell growth and apoptosis caused by multiple signal transduction pathways. Dexamethasone (DEX) treatment inhibited cell growth and stimulated cell death in S49-NEO cells. Although S49 Bcl-2 cells exhibited a similar antiproliferative response, they failed to die in response to steroid treatment. Western blot analysis revealed no difference in the levels of glucocorticoid receptor protein in the two cell lines, and both responded to glucocorticoid with a profound inhibition of protein synthesis. Cycloheximide (CX) and A23187 also had antiproliferative and cell killing effects in both cell types, although higher concentrations of each agent were needed to kill S49-Bcl-2 cells. To determine whether the loss of viability in response to these drugs was due to apoptosis, cells were examined morphologically and DNA integrity was examined by gel electrophoresis.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8005392 TI - Protein kinase C beta I and beta II are differentially expressed in the developing glomerulus. AB - In the pre- and postnatal period of kidney development, proliferation with subsequent functional maturation of intrinsic glomerular mesangial cells (MCs) continues within the existing framework. Recent work has suggested that PKC beta isoform is responsible for the proliferation observed during maturation. We sought to ascertain whether PKC beta isoform expression is altered during the development of the mesangium. MCs were subcultured from glomerular explants of Sprague-Dawley rat kidneys, days 1, 3, 5, 8, 15 postnatally, and adult. MCs from rat kidneys postnatally days 1-5 proliferated at a significantly greater rate than adult [ > 1.169-fold, P < 0.01] but term day 8 cells did not [ < 1.34-fold, not significant)] as assessed by [3H]thymidine incorporation. Western blot analysis using isoform specific antibodies was performed on confluent neonatal and adult MC. We observed that all neonatal and adult MC express beta I PKC (n = 8 kidneys from separate primaries for each date and adult). However, unlike adult MCs, neonatal MC express beta II in postnatal days 1-5 and none thereafter. Immunofluorescent staining of postnatal kidneys confirmed that PKC beta II is present in neonatal MC up to day 5. By day 8, staining of mesangium with PKC beta II begins to disappear and assumes a parietal epithelial pattern. In adult kidneys, there was only PKC beta II staining of the parietal epithelial cells. Our results demonstrate that differential expression of PKC beta II closely parallels the proliferative behavior of the MCs of the maturing glomerulus. Therefore, PKC beta II expression and activation may play a critical role in development. PMID- 8005393 TI - Inhibition of apoptosis as a mechanism of tumor promotion. AB - Recent evidence supports the concept that tumor growth in vivo depends on evasion of normal homeostatic control mechanisms that operate through induction of cell death by apoptosis. This study tested the hypothesis that a common property shared by known or suspected tumor promoters is the ability to block the process of apoptosis. A total of 10 tumor promoters were tested and all were found to inhibit DNA fragmentation and cell death of 7 different cell lines triggered into apoptosis by diverse agents. Resistance to apoptosis could be induced rapidly (within 1 h) by treating with relatively high concentrations of promoters. However, low physiological concentrations of promoters could also induce complete resistance to apoptosis after prolonged exposure (5-15 days of culture). Like tumor promotion in vivo, promoter-induced resistance to apoptosis was reversible after culturing in the absence of promoter. These findings provide new insight into the mechanism of tumor promotion and suggest a novel in vitro screening assay to detect new tumor-promoting agents in the environment. PMID- 8005394 TI - Poliomyelitis eradication: a continuing story. PMID- 8005395 TI - Dental laboratory owner's perspectives: factors in selection and termination of business relationships. PMID- 8005396 TI - Clinical evaluation of an electronic anesthesia system. PMID- 8005397 TI - Clinical effectiveness of lysine in treating recurrent aphthous ulcers and herpes labialis. PMID- 8005398 TI - Current therapeutic management of recurrent herpes labialis. PMID- 8005399 TI - Microleakage of 5 third-generation dentinal bonding systems. PMID- 8005400 TI - Rooting out guilt and anxiety. PMID- 8005401 TI - Tooth movement through directed tongue and lip pressure. PMID- 8005402 TI - HIV infection and necrotizing stomatitis. PMID- 8005403 TI - Simultaneous apical and cervical idiopathic external root resorption. PMID- 8005404 TI - Preferred needle lengths for inferior alveolar anesthesia. PMID- 8005405 TI - Precautions in dental treatment of patients with mitral valve prolapse. PMID- 8005406 TI - Coordination of patient care and consultation between the dentist and physician. PMID- 8005407 TI - Use of rectified turpentine oil to soften gutta-percha. PMID- 8005408 TI - Ludwig's angina. PMID- 8005409 TI - Dentists' age and manual dexterity. Are younger or older dentists better practitioners? PMID- 8005410 TI - P element-mediated in vivo deletion analysis of white-apricot: deletions between direct repeats are strongly favored. AB - We have isolated and characterized deletions arising within a P transposon, P[hswa], in the presence of P transposase. P[hswa] carries white-apricot (wa) sequences, including a complete copia element, under the control of an hsp70 promoter, and resembles the original wa allele in eye color phenotype. In the presence of P transposase, P[hswa] shows a high overall rate (approximately 3%) of germline mutations that result in increased eye pigmentation. Of 234 derivatives of P[hswa] with greatly increased eye pigmentation, at least 205 carried deletions within copia. Of these, 201 were precise deletions between the directly repeated 276-nucleotide copia long terminal repeats (LTRs), and four were unique deletions. High rates of transposase-induced precise deletion were observed within another P transposon carrying unrelated 599 nucleotide repeats (yeast 2 mu FLP; recombinase target sites) separated by 5.7 kb. Our observation that P element-mediated deletion formation occurs preferentially between direct repeats suggests general methods for controlling deletion formation. PMID- 8005411 TI - Drosophila P element transposase induces male recombination additively and without a requirement for P element excision or insertion. AB - P element dysgenesis-associated male recombination in Drosophila was examined with a selective system focused upon a section of the third chromosome divided into eight recombination segments. Tests compared crossing over in the presence of none, one and two doses of P(delta 2-3)(99B), a non-mobile transposase source, in the absence of a mobilizable P element target in the genome. In the presence of the P transposase source, and without a P element target, significant male recombination occurred in genomic regions physically separated from the P(delta 2 3) site. Using two doses of P(delta 2-3) without a P element target, the male recombination rate doubled, and 90% of the crossovers occurred in the pericentric region. The distribution of recombination events, in the absence of P element targets approximates that seen in studies of radiation induced mitotic crossing over and the metaphase chromosome map. Another experiment examined the effects of one dose of P(delta 2-3) on a genome with a single P element target, P(lArB)(87C9), in the third recombination segment. Crossovers increased 58-fold in the immediate region of the P element target. PMID- 8005413 TI - Decline in heterozygosity under full-sib and double first-cousin inbreeding in Drosophila melanogaster. AB - The effects of inbreeding on heterozygosities and reproductive fitness were determined by carrying out full-sib and double first-cousin inbreeding in Drosophila melanogaster populations for up to 18 generations. Parents were scored each generation for five or six polymorphic enzyme loci, and progeny numbers per pair were recorded. Inbreeding depression, in the form of significant reductions in progeny numbers and significant extinction of lines, was observed. Heterozygosity decreased at a significantly slower rate than predicted, being about 80% of expected. The full-sib and double first-cousin treatments showed similar disagreement with expectations over comparable ranges of inbreeding. Natural selection was shown to favor heterozygotes in the inbred lines. Associative overdominance was the most probable explanation for the slower than expected decline in heterozygosity. PMID- 8005412 TI - Unusual properties of regulatory DNA from the Drosophila engrailed gene: three "pairing-sensitive" sites within a 1.6-kb region. AB - We have previously shown that a 2-kb fragment of engrailed DNA can suppress expression of a linked marker gene, white, in the P element vector CaSpeR. This suppression is dependent on the presence of two copies of engrailed DNA containing P elements (P[en]) in proximity in the Drosophila genome (either in cis or in trans). In this study, the 2-kb fragment was dissected and found to contain three fragments of DNA which could mediate white suppression [called "pairing-sensitive sites" (PS)]. A PS site was also identified in regulatory DNA from the Drosophila escargot gene. The eye colors of six different P[en] insertions in the escargot gene suggest an interaction between P[en]-encoded and genome-encoded PS sites. I hypothesize that white gene expression from P[en] is repressed by the formation of a protein complex which is initiated at the engrailed PS sites and also requires interactions with flanking genomic DNA. Genes were sought which influence the function of PS sites. Mutations in some Polycomb and trithorax group genes were found to affect the eye color from some P[en] insertion sites. However, different mutations affected expression from different P[en] insertion sites and no one mutation was found to affect expression from all P[en] insertion sites examined. These results suggest that white expression from P[en] is not directly regulated by members of the Polycomb and trithorax group genes, but in some cases can be influenced by them. I propose that engrailed PS sites normally act to promote interactions between distantly located engrailed regulatory sites and the engrailed promoter. PMID- 8005414 TI - Differential effects of Sex-lethal mutations on dosage compensation early in Drosophila development. AB - In response to the primary sex determination signal, X chromosome dose, the Sex lethal gene controls all aspects of somatic sex determination and differentiation, including X chromosome dosage compensation. Two complementary classes of mutations have been identified that differentially affect Sxl somatic functions: (1) those impairing the "early" function used to set developmental pathway choice in response to the sex determination signal and (2) those impairing "late" functions involved in maintaining the pathway choice independent of the initiating signal and/or in directing differentiation. This "early vs. late" distinction correlates with a switch in promoter utilization from SxlPe to SxlPm at the blastoderm stage and a corresponding switch from transcriptional to RNA splicing control. Here we characterize five partial-loss-of-function Sxl alleles to explore a distinction between "early vs. late" functioning of Sxl in dosage compensation. Assaying for dosage compensation during the blastoderm stage, we find that the earliest phase of the dosage compensation process is controlled by products of the early Sxl promoter, SxlPe. Hence, in addition to triggering the sexual pathway decision of cells, products derived from SxlPe also control early dosage compensation, the first manifestation of sexually dimorphic differentiation. The effects of mutant Sxl alleles on early dosage compensation are consistent with their previous categorization as early vs. late defective with respect to their effects on pathway initiation. Results reported here suggest that the dosage compensation regulatory genes currently known to function downstream of Sxl, genes known as the "male-specific lethals," do not control all aspects of dosage compensation either at the blastoderm stage or later in development. In the course of this study, we also discovered that the canonical early defective allele, Sxlf9, which is impaired in its ability to establish the female developmental pathway commitment, is likely to be defective in the stability and/or functioning of products derived from SxlPe, rather than in the ability of SxlPe to respond to the chromosomal sex determination signal. PMID- 8005415 TI - Molecular and cytogenetical characterization of the 10A1-2 band and adjoining region in the Drosophila melanogaster polytene X chromosome. AB - Some 300 kb of DNA from the 9F12-10A7 X chromosome region (seven bands) uncovered by Df(1)vL3 were cloned and 31 break points of chromosome rearrangements within the region were mapped. Positions of 12 genes found earlier in genetic saturation experiments, transcripts and P element-induced mutations were located on the physical map using either chromosome rearrangements or Southern blot hybridizations. Data on the position of the break points, genes and polytene chromosome bands allow the following conclusions to be made. (1) The size of the bands in the region varies between 4 kb (10A6 and 7) and 183-195 kb (10A1-2). The compaction ratio of DNA in bands varies from 8-36 (10A6 + 7) to 151-161 (10A1-2). Therefore, fine and thick bands appear to have different kinds of DNP packaging. (2) The bands differ in genetic content. Fine bands contain from one to three genes. In contrast, the 10A1-2 band contains three genes and at least six transcribed DNA fragments. (3) Comparison of genetic and physical maps shows that in this region 0.01 centiMorgan corresponds to 3.3 kb of DNA. PMID- 8005416 TI - Evidence that the Drosophila olfactory mutant smellblind defines a novel class of sodium channel mutation. AB - The smellblind (sbl) gene of Drosophila is associated with olfactory defects, and the paralytic (para) gene encodes a voltage-gated sodium channel. sbl and para have similar genetic map positions, many combinations of sbl and para mutations fail to complement, and two sbl mutations contain molecular lesions within the para transcription unit. sbl mutations also behave like para mutations in that they are enhanced by the mutation no action potential temperature-sensitive (mlenapts1). The simplest interpretation of these results is that sbl and para are the same gene. Two sbl mutations produce olfactory defects not characteristic of classic sodium channel mutations and do not show typical heat-sensitive paralysis, suggesting that these sbl mutants define a novel class of sodium channel mutation. PMID- 8005417 TI - Sex determination in the fly Megaselia scalaris, a model system for primary steps of sex chromosome evolution. AB - The fly Megaselia scalaris Loew possesses three homomorphic chromosome pairs; 2 is the sex chromosome pair in two wild-type laboratory stocks of different geographic origin (designated "original" sex chromosome pair in this paper). The primary male-determining function moves at a very low rate to other chromosomes, thereby creating new Y chromosomes. Random amplified polymorphic DNA markers obtained by polymerase chain reaction with single decamer primers and a few available phenotypic markers were used in testcrosses to localize the sex determining loci and to define the new sex chromosomes. Four cases are presented in which the primary male-determining function had been transferred from the original Y chromosome to a new locus either on one of the autosomes or on the original X chromosome, presumably by transposition. In these cases, the sex determining function had moved to a different locus without an obvious cotransfer of other Y chromosome markers. Thus, with Megaselia we are afforded an experimental system to study the otherwise hypothetical primary stages of sex chromosome evolution. An initial molecular differentiation is apparent even in the new sex chromosomes. Molecular differences between the original X and Y chromosomes illustrate a slightly more advanced stage of sex chromosome evolution. PMID- 8005418 TI - Mitochondrial DNA variation and the evolution of Robertsonian chromosomal races of house mice, Mus domesticus. AB - The house mouse, Mus domesticus, includes many distinct Robertsonian (Rb) chromosomal races with diploid numbers from 2n = 22 to 2n = 38. Although these races are highly differentiated karyotypically, they are otherwise indistinguishable from standard karyotype (i.e., 2n = 40) mice, and consequently their evolutionary histories are not well understood. We have examined mitochondrial DNA (mtDNA) sequence variation from the control region and the ND3 gene region among 56 M. domesticus from Western Europe, including 15 Rb populations and 13 standard karyotype populations, and two individuals of the sister species, Mus musculus. mtDNA exhibited an average sequence divergence of 0.84% within M. domesticus and 3.4% between M. domesticus and M. musculus. The transition/transversion bias for the regions sequenced is 5.7:1, and the overall rate of sequence evolution is approximately 10% divergence per million years. The amount of mtDNA variation was as great among different Rb races as among different populations of standard karyotype mice, suggesting that different Rb races do not derive from a single recent maternal lineage. Phylogenetic analysis of the mtDNA sequences resulted in a parsimony tree which contained six major clades. Each of these clades contained both Rb and standard karyotype mice, consistent with the hypothesis that Rb races have arisen independently multiple times. Discordance between phylogeny and geography was attributable to ancestral polymorphism as a consequence of the recent colonization of Western Europe by mice. Two major mtDNA lineages were geographically localized and contained both Rb and standard karyotype mice. The age of these lineages suggests that mice have moved into Europe only within the last 10,000 years and that Rb populations in different geographic regions arose during this time. PMID- 8005419 TI - Variegated phenotype and developmental methylation changes of a maize allele originating from epimutation. AB - Two instances of genetic transmission of spontaneous epimutation of the maize P rr gene were identified. Transmission gave rise to two similar, moderately stable alleles, designated P-pr-1 and P-pr-2, that exhibited Mendelian behavior. Both isolates of P-pr conditioned a variable and variegated phenotype, unlike the uniform pigmentation conditioned by P-rr. Extensive genomic analysis failed to reveal insertions, deletions or restriction site polymorphisms between the new allele and its progenitor. However, methylation of the P gene was increased in P pr relative to P-rr, and was greatly reduced (though not lost) in a revertant to uniform pigmentation. Variability in pigmentation conditioned by P-pr correlated with variability in transcript levels of the P gene, and both correlated inversely with variability in its methylation. Part of the variability in methylation could be accounted for by a developmental decrease in methylation in all tissues of plants carrying P-pr. We hypothesize that the variegated phenotype results from a general epigenetic pathway which causes a progressive decrease in methylation and increase in expression potential of the P gene as a function of cell divisions in each meristem of the plant. This renders all tissues chimeric for a functional gene; chimerism is visualized as variegation only in pericarp due to the tissue specificity of P gene expression. Therefore, this allele that originates from epimutation may exemplify an epigenetic mechanism for variegation in maize. PMID- 8005420 TI - Genetic evidence of Mutator-induced deletions in the short arm of chromosome 9 of maize. II. wd deletions. AB - Analyses of 113 putative Mutator-induced events involving the yg2 locus of chromosome 9 revealed that 11 of these events were deletions that produce albino seedlings when homozygous. This phenotype is characteristic of wd (white deficiency) deletions. All 11 wd-Mu deletions failed to complement wd1 and pyd1 (pale-yellow deficiency). Nine of the wd-Mu deletions were analyzed cytologically. Two were found to be terminal deletions and seven were internal deletions. Two of the seven had normal pairing throughout the terminal region involved in the pyd1 and wd1 deletions. Because genetic tests established that deletions were present in these two stocks, these deletions were probably too short to disrupt the pairing of the homologous chromosomes. Mechanisms by which the Mutator system might generate these deletions are discussed. PMID- 8005421 TI - Gene marker loss induced by the transposable element, En, in maize. AB - The En/Spm transposable element system in maize includes the functional element, En/Spm and the receptor element I/dSpm. An En receptor has been found that shows En-induced breakage. This En-responsive receptor (designated I836518) is located on the short arm of chromosome 9, proximal to Wx. In the presence of En, markers distal to the receptor show a loss of gene expression. Kernels heterozygous for aleurone and endosperm marker genes have a variegated appearance. The hypothesis is advanced that this variegation represents a physical loss of the chromosome segments carrying the genes distal to the receptor position. It is the first case of an En-controlled breakage event. PMID- 8005422 TI - Coordinate suppression of mutations caused by Robertson's mutator transposons in maize. AB - Transposable elements from the Robertson's Mutator family are highly active insertional mutagens in maize. However, mutations caused by the insertion of responder (non-autonomous) elements frequently depend on the presence of active regulator (autonomous) elements for their phenotypic effects. The hcf106::Mu1 mutation has been previously shown to depend on Mu activity in this way. The dominant Lesion-mimic 28 mutation also requires Mu activity for its phenotypic effects. We have used double mutants to show that the loss of Mu activity results in the coordinate suppression of both mutant phenotypes. This loss can occur somatically resulting in large clones of cells that have a wild-type phenotype. Autonomous and non-autonomous Mutator elements within these clones are insensitive to digestion with methylation-sensitive enzymes, suggesting extensive methylation of CG and non-CG cytosine residues. Our data are consistent with the sectors being caused by the cycling of MuDR regulatory elements between active and inactive phases. The pattern of sectors suggests that they are clonal and that they are derived from the apical cells of the vegetative shoot meristem. We propose that these cells are more likely to undergo epigenetic loss of Mu activity because of their longer cell division cycle during shoot growth. Coordinate suppression of unlinked mutations can be used to perform mosaic analysis in maize. PMID- 8005423 TI - Paternally inherited chloroplast polymorphism in Pinus: estimation of diversity and population subdivision, and tests of disequilibrium with a maternally inherited mitochondrial polymorphism. AB - We have surveyed a chloroplast DNA restriction fragment length polymorphism in 745 individuals, distributed rangewide in eight allopatric natural populations of jack pine (Pinus banksiana Lamb.) and eight allopatric natural populations of lodgepole pine (Pinus contorta Dougl.). The polymorphic region of the chloroplast genome is located near duplicated psbA genes. Fourteen length variants were found in the survey, and these variants distinguished the two species qualitatively. Variant diversities were high in both species (hes = 0.43 in jack pine; hes = 0.44 in lodgepole pine). Population subdivision was weak within and among lodgepole pine subspecies and in jack pine (i.e., theta values were less than 0.05). This weak subdivision is compatible with theoretical predictions for paternally inherited markers in wind-pollinated outcrossers, as well as for polymorphisms with high length mutation rates. If these populations are at a drift-migration equilibrium, the chloroplast DNA restriction fragment data and previous mitochondrial frequency data from the same individuals are consistent with gene flow that is differential through seeds and pollen. The new data have permitted the first empirical tests of disequilibrium between maternally and paternally inherited factors. As expected, these tests failed to detect convincing evidence of nonrandom association between chloroplast and mitochondrial variants. PMID- 8005424 TI - Mapping quantitative trait loci in crosses between outbred lines using least squares. AB - The use of genetic maps based upon molecular markers has allowed the dissection of some of the factors underlying quantitative variation in crosses between inbred lines. For many species crossing inbred lines is not a practical proposition, although crosses between genetically very different outbred lines are possible. Here we develop a least squares method for the analysis of crosses between outbred lines which simultaneously uses information from multiple linked markers. The method is suitable for crosses where the lines may be segregating at marker loci but can be assumed to be fixed for alternative alleles at the major quantitative trait loci (QTLs) affecting the traits under analysis (e.g., crosses between divergent selection lines or breeds with different selection histories). The simultaneous use of multiple markers from a linkage group increases the sensitivity of the test statistic, and thus the power for the detection of QTLs, compared to the use of single markers or markers flanking an interval. The gain is greater for more closely spaced markers and for markers of lower information content. Use of multiple markers can also remove the bias in the estimated position and effect of a QTL which may result when different markers in a linkage group vary in their heterozygosity in the F1 (and thus in their information content) and are considered only singly or a pair at a time. The method is relatively simple to apply so that more complex models can be fitted than is currently possible by maximum likelihood. Thus fixed effects of background genotype can be fitted simultaneously with the exploration of a single linkage group which will increase the power to detect QTLs by reducing the residual variance. More complex models with several QTLs in the same linkage group and two locus interactions between QTLs can similarly be examined. Thus least squares provides a powerful tool to extend the range of crosses from which QTLs can be dissected whilst at the same time allowing flexible and realistic models to be explored. PMID- 8005425 TI - Luria-Delbruck fluctuation experiments: design and analysis. AB - Luria and Delbruck, in a seminal paper, introduced fluctuation analysis primarily as a means to elucidate the timing of mutation in relation to the imposition of selective conditions. Their work, and subsequently that of LEA and COULSON, established also a basis for measuring the frequency of mutational events. The several estimators proposed by these authors differ both in complexity and in efficiency, and the published literature relies mainly on the less efficient but computationally trivial estimators. The estimators as originally proposed assume that all mutants occurring in culture will be counted in the subsequent assay, but a relaxation of this assumption suggests an alternative experimental design and alternative estimators which offer advantages over those currently in common use. PMID- 8005426 TI - Detection of genetic interference: simulation studies and mouse data. AB - Genetic chiasma interference occurs when the occurrence of one crossover (or chiasma) influences the probability of another crossover occurring nearby. We investigated, by simulation studies, the power of three statistical methods to detect interference. Neither the traditional three-locus method nor a multiplicative model approach are very powerful, while a multilocus-feasible map function approach is more powerful, particularly as the number of loci increases. We show that the power to detect interference is quite sensitive to the underlying type of interference. When we tested for interference in two mouse data sets (from chromosomes 1 and 12), we found significant evidence of positive interference. PMID- 8005427 TI - Sturtevant's mantle and the (lost?) art of chromosome mechanics. PMID- 8005428 TI - DNA sequence effects on single base deletions arising during DNA polymerization in vitro by Escherichia coli Klenow fragment polymerase. AB - Most single base deletions detected after DNA polymerization in vitro directed by either Escherichia coli DNA polymerase I or its Klenow fragment are opposite Pu in the template. The most frequent mutations were previously found to be associated with the consensus template context 5'-PyTPu-3'. In this study, the predictive power of the consensus sequence on single base deletion frequencies was directly tested by parallel comparison of mutations arising in four related DNAs differing by a single base. G, a deletion hotspot within the template context 5'-TTGA-3', was substituted by each of the 3 other bases. Previous studies had shown that deletions opposite the G were frequent but that deletions opposite its neighboring A were never detected. Based on the predictions of the consensus, the substitution of T for G should produce frequent deletions opposite the neighboring A due to its new 5'-TTTA-3' template context. This prediction was fulfilled; no deletions of this A were detected in the other templates. The consensus further predicted that deletions opposite template C would be lower than those opposite either A or G at the same site and this prediction was also fulfilled. The C substitution also produced a new hotspot for 1 bp deletions 14 bp away. The new hotspot depends on quasi-palindromic misalignment of the newly synthesized DNA strand during polymerization; accurate, but ectopically templated synthesis is responsible for this mutagenesis. Mutations templated by quasi palindromic misalignments have previously been recognized when they produced complex sequence changes; here we show that this mechanism can produce frequent single base deletions. The unique stimulation of misalignment mutagenesis by the C substitution in the template is consistent with the singular ability of C at that site to contribute to extended complementary pairing during the DNA misalignment that precedes mutagenesis. PMID- 8005429 TI - Complex frameshift mutations mediated by plasmid pKM101: mutational mechanisms deduced from 4-aminobiphenyl-induced mutation spectra in Salmonella. AB - We used colony probe hybridization and polymerase chain reaction/DNA sequence analysis to determine the mutations in approximately 2,400 4-aminobiphenyl (4-AB) +S9-induced revertants of the -1 frameshift allele hisD3052 and of the base substitution allele hisG46 of Salmonella typhimurium. Most of the mutations occurred at sites containing guanine, which is the primary base at which 4-AB forms DNA adducts. A hotspot mutation involving the deletion of a CG or GC within the sequence CGCGCGCG accounted for 100 and 99.9%, respectively, of the reversion events at the hisD3052 allele in the pKM101 plasmid-minus strains TA1978 (uvr+) and TA1538 (delta uvrB). In strain TA98 (delta uvrB, pKM101), which contained the SOS DNA repair system provided by the pKM101 plasmid, approximately 85% of the revertants also contained the hotspot deletion; the remaining approximately 15% contained one of two types of mutations: (1) complex frameshifts that can be described as a -2 or +1 frameshift and an associated base substitution and (2) deletions of the CC or GG sequences that flank the hotspot site (CCGCGCGCGG). We propose a misincorporation/slippage model to account for these mutations in which (1) pKM101-mediated misincorporation and translesion synthesis occurs across a 4 AB-adducted guanine; (2) the instability of such a mispairing and/or the presence of the adduct leads to strand slippage in a run of repeated bases adjacent to the adducted guanine; and (3) continued DNA synthesis from the slipped intermediate produces a frameshift associated with a base substitution. This model readily accounts for the deletion of the CC or GG sequences flanking the hotspot site, indicating that these mutations are, in fact, complex mutations in disguise (i.e., cryptic complex frameshifts). The inferred base-substitution specificity associated with the complex frameshifts at the hisD3052 allele (primarily G.C- >T.A transversions) is consistent with the finding that 4-AB induced primarily G.C-->T.A transversions at the hisG46 base-substitution allele. The model also provides a framework for understanding the different relative mutagenic potencies of 4-AB at the two alleles in the various DNA repair backgrounds of Salmonella. PMID- 8005430 TI - Endpoint bias in large Tn10-catalyzed inversions in Salmonella typhimurium. AB - A genetic strategy identified Salmonella typhimurium strains carrying large (> 40 kb) Tn 10-catalyzed inversions; the inverted segments were characterized by XbaI digestion and pulsed field gel electrophoresis. Two size classes of large inversions were found. More than half of the inversions extended 40-80 kb either clockwise or counterclockwise of the original Tn10 site. The remaining inversions extended up to 1620 kb (33% of the genome), but the distal endpoints of these inversions were not randomly scattered throughout the chromosome. Rather, each Tn10 repeatedly yielded similar (though not identical) inversions. The biased endpoint selection may reflect the limited search for target DNA sequences by the Tn10 transposase, and the spatial proximity of the donor and target regions in the folded S. typhimurium nucleoid. Using this interpretation, the data suggest that DNA sequences 40-80 kb clockwise and counterclockwise of the insertion site are in spatial proximity with the insertion, perhaps reflecting the organization of DNA into approximately 120-kb nucleoid domains. In addition, the data predict the spatial proximity of several distant DNA regions, including DNA sequences equidistant from the origin of DNA replication. PMID- 8005431 TI - Enhancement of telomere-plasmid segregation by the X-telomere associated sequence in Saccharomyces cerevisiae involves SIR2, SIR3, SIR4 and ABF1. AB - We have previously shown that circular replicating plasmids that carry yeast telomere repeat sequence (TG1-3) tracts segregate efficiently relative to analogous plasmids lacking the TG1-3 tract and this efficient segregation is dependent upon RAP1. While a long TG1-3 tract is sufficient to improve plasmid segregation, the segregation efficiency of telomere plasmids (TEL-plasmids) is enhanced when the X-Telomere Associated Sequence (X-TAS) is also included on the plasmids. We now demonstrate that the enhancement of TEL-plasmid segregation by the X-TAS depends on SIR2, SIR3, SIR4 and ABF1 in trans and requires the Abf1p binding site within the X-TAS. Mutation of the Abf1p-binding site within the X TAS results in TEL-plasmids that are no longer affected by mutations in SIR2, SIR3 or SIR4, despite the fact that other Abf1p-binding sites are present on the plasmid. Mutation of the ARS consensus sequence within the X-TAS converts the X TAS from an enhancer element to a negative element that interferes with TEL plasmid segregation in a SIR-dependent manner. Thus, telomere associated sequences interact with TG1-3 tracts on the plasmid, suggesting that the TASs have an active role in modulating telomere function. PMID- 8005432 TI - Transient, meiosis-induced expression of the rec6 and rec12 genes of Schizosaccharomyces pombe. AB - Two meiotic recombination genes, rec6 and rec12, from Schizosaccharomyces pombe have been cloned by genetic complementation and their DNA sequences determined. Gene replacements demonstrated that the cloned fragments contained the rec6 and rec12 genes. Further analysis showed that the functional rec6 gene was within a 1.3-kb fragment and rec12 within a 1.7-kb fragment. The nucleotide sequences of these fragments revealed open reading frames (ORFs) predicting 143 amino acids for the rec6 gene product and 139 amino acids for the rec12 gene product. After pat1-114 temperature-induced meiosis, the transcripts of rec6 and rec12 were induced to maximal levels at 2-3 hr, at about the time of premeiotic DNA synthesis, but were present at much lower levels before and after this time. The transient induction of the transcripts and the phenotypes of the mutants suggest that the rec6 and rec12 gene products are involved primarily in the early steps of meiotic recombination in S. pombe. Near the rec6 gene are two additional ORFs potentially encoding proteins with homology to ribosomal protein S7 of Saccharomyces cerevisiae (ORF137) and to the homeodomain of developmental regulatory proteins (ORF201). The roles of these S. pombe ORFs remain to be determined. PMID- 8005433 TI - Epistasis analysis of suppressor mutations that allow HO expression in the absence of the yeast SW15 transcriptional activator. AB - We have examined mutations which overcome the requirement for SW15-dependent transcriptional activation of the Saccharomyces cerevisiae HO gene. We show that the RPD3 gene is the same as SDI2, and that SIN4 is the same as the TSF3 and SDI3 genes. We have also identified a new swi5 suppressor, RGR1. The RGR1 gene was identified originally as a negative regulator of SUC2. Epistasis analysis indicates that six swi5 suppressor genes function in four distinct pathways, with RPD3 and SIN3 in one pathway, RGR1 and SIN4 in a second pathway, and SDI4 and SIN5 each in distinct pathways. Finally, we show that complete suppression of the swi5 defect in HO expression by sin5 requires the wild-type ACE2 gene. This suggests that one function of SIN5 is to prevent ACE2, a SWI5 homolog, from activating HO expression. PMID- 8005435 TI - Genetic variation of the repeated MAL loci in natural populations of Saccharomyces cerevisiae and Saccharomyces paradoxus. AB - In Saccharomyces cerevisiae, the gene functions required to ferment the disaccharide maltose are encoded by the MAL loci. Any one of five highly sequence homologous MAL loci identified in various S. cerevisiae strains (called MAL1, 2, 3, 4 and 6) is sufficient to ferment maltose. Each is a complex of three genes encoding maltose permease, maltase and a transcription activator. This family of loci maps to telomere-linked positions on different chromosomes and most natural strains contain more than one MAL locus. A number of naturally occurring, mutant alleles of MAL1 and MAL3 have been characterized which lack one or more of the gene functions encoded by the fully functional MAL loci. Loss of these gene functions appears to have resulted from mutation and/or rearrangement within the locus. Studies to date concentrated on the standard maltose fermenting strains of S. cerevisiae available from the Berkeley Yeast Stock Center collection. In this report we extend our genetic analysis of the MAL loci to a number of maltose fermenting and nonfermenting natural strains of S. cerevisiae and Saccharomyces paradoxus. No new MAL loci were discovered but several new mutant alleles of MAL1 were identified. The evolution of this gene family is discussed. PMID- 8005434 TI - The chromosome end in yeast: its mosaic nature and influence on recombinational dynamics. AB - Yeast chromosome ends are composed of several different repeated elements. Among six clones of chromosome ends from two strains of Saccharomyces cerevisiae, at least seven different repeated sequence families were found. These included the previously identified Y' and X elements. Some families are highly variable in copy number and location between strains of S. cerevisiae, while other elements appear constant in copy number and location. Three repeated sequence elements are specific to S. cerevisiae and are not found in its evolutionarily close relative, Saccharomyces paradoxus. Two other repeated sequences are found in both S. cerevisiae and S. paradoxus. None of those described here is found (by low stringency DNA hybridization) in the next closest species, Saccharomyces bayanus. The loosely characterized X element is now more precisely defined. X is a composite of at least four small (ca. 45-140 bp) sequences found at some, but not all, ends. There is also a potential "core" X element of approximately 560 bp which may be found at all ends. Distal to X, only one of six clones had (TG1-3)n telomere sequence at the junction between X and Y'. The presence of these internal (TG1-3)n sequences correlates with the ability of a single Y' to expand into a tandem array of Y's by unequal sister chromatid exchange. The presence of shared repeated elements proximal to the X region can override the strong preference of Y's to recombine ectopically with other Y's of the same size class. The chromosome ends in yeast are evolutionarily dynamic in terms of subtelomeric repeat structure and variability. PMID- 8005436 TI - Evidence that TUP1/SSN6 has a positive effect on the activity of the yeast activator HAP1. AB - The activity of the yeast transcriptional activator HAP1 is controlled by heme and the heme effect is mediated through the heme domain of HAP1. In this report, we show that HAP1 activity is significantly reduced in strains deleted of TUP1 or SSN6, and addition of a heme analog does not allow HAP1 to regain its full activity. Deletion of the heme domain alleviates the requirement for TUP1/SSN6. The results suggest that TUP1/SSN6 have a positive effect on the activity of HAP1 and this effect is mediated through the heme domain. Although TUP1/SSN6 generally repress transcription of many genes, our data indicate they may have positive effect on the expression of certain genes. PMID- 8005437 TI - A novel allele of HAP1 causes uninducible expression of HEM13 in Saccharomyces cerevisiae. AB - Transcription of HEM13 in Saccharomyces cerevisiae is repressed by heme and oxygen. We have isolated two mutants in which expression of HEM13 is aberrant. The mutant alleles in these strains represent two different alleles of HAP1. HAP1 encodes an activator protein whose DNA binding activity is stimulated by heme, and is required for the transcription of CYC1, ROX1 and a number of other heme dependent genes. One of our mutant alleles confers a phenotype much like that of the hap1::LEU2 allele. Expression of HEM13 in a strain with this mutation is elevated under repressing conditions and not fully inducible in the absence of heme. The other mutant allele of HAP1 we uncovered confers a novel phenotype. A strain containing this allele exhibits heme-independent expression of CYC1 and ROX1 and uninducible expression of HEM13 and ANB1. The mutation associated with this novel allele of HAP1 was localized to a glycine to aspartate change in amino acid 235 of HAP1, between the DNA binding and heme responsive domains. DNA binding assays demonstrated that the protein made from this HAP1 allele retains the ability to bind DNA, but that unlike wild-type HAP1 protein, this binding is not stimulated by heme. PMID- 8005439 TI - Efficient targeted integration at leu1-32 and ura4-294 in Schizosaccharomyces pombe. AB - Homologous integration into the fission yeast Schizosaccharomyces pombe has not been well characterized. In this study, we have examined integration of plasmids carrying the leu1+ and ura4+ genes into their chromosomal loci. Genomic DNA blot analysis demonstrated that the majority of transformants have one or more copies of the plasmid vector integrated via homologous recombination with a much smaller fraction of gene conversion to leu1+ or ura4+. Non-homologous recombination events were not observed for either gene. We describe the construction of generally useful leu1+ and ura4+ plasmids for targeted integration at the leu1-32 and ura4-294 loci of S. pombe. PMID- 8005438 TI - Extragenic suppressors of Saccharomyces cerevisiae prp4 mutations identify a negative regulator of PRP genes. AB - The PRP4 gene encodes a protein that is a component of the U4/U6 small nuclear ribonucleoprotein particle and is necessary for both spliceosome assembly and pre mRNA splicing. To identify genes whose products interact with the PRP4 gene or gene product, we isolated second-site suppressors of temperature-sensitive prp4 mutations. We limited ourselves to suppressors with a distinct phenotype, cold sensitivity, to facilitate analysis of mutants. Ten independent recessive suppressors were obtained that identified four complementation groups, spp41, spp42, spp43 and spp44 (suppressor of prp4, numbers 1-4). spp41-spp44 suppress the pre-mRNA splicing defect as well as the temperature-sensitive phenotype of prp4 strains. Each of these spp mutations also suppresses prp3; spp41 and spp42 suppress prp11 as well. Neither spp41 nor spp42 suppressors null alleles of prp3 or prp4, indicating that the suppression does not occur via a bypass mechanism. The spp41 and spp42 mutations are neither allele- nor gene-specific in their pattern of suppression and do not result in a defect in pre-mRNA splicing. Thus the SPP41 and SPP42 gene products are unlikely to participate directly in mRNA splicing or interact directly with Prp3p or Prp4p. Expression of PRP3-lacZ and PRP4-lacZ gene fusions is increased in spp41 strains, suggesting that wild-type Spp41p represses expression of PRP3 and PRP4. SPP41 was cloned and sequenced and found to be essential. spp43 is allelic to the previously identified suppressor srn1, which encodes a negative regulator of gene expression. PMID- 8005440 TI - The small ribosomal subunit RNA isoforms in Plasmodium cynomolgi. AB - We report the isolation, characterization and analysis of the small subunit rRNA genes in Plasmodium cynomolgi (Ceylon). As in other Plasmodium species, these genes are present in low copy number, are unlinked and form two types that are distinct in sequence and are expressed stage specifically. The asexually expressed (type A) genes are present in four copies in the Ceylon- and in five copies in the Berok-strain. Surprisingly, the sexually expressed (type B) gene is present in a single copy. The vast majority of the differences between gene types is confined to the variable regions. The pattern of divergence is different from that observed in Plasmodium berghei or in Plasmodium falciparum. Analysis of the small subunit rRNA sequences of P. cynomolgi, P. berghei and P. falciparum, indicates that the two gene types do not evolve independently but rather interact (through gene conversion or some form of recombination) to such an extent as to erase whatever stage-specific sequence signatures they may have had in the last common ancestor. PMID- 8005441 TI - A suppressor of a mating-type limited zygotic lethal allele also suppresses uniparental chloroplast gene transmission in Chlamydomonas monoica. AB - Uniparental inheritance of Chlamydomonas chloroplast genes is thought to involve modification of maternal (mt+) chloroplast genomes to protect against a nuclease that is activated after gamete fusion. The mating-type limited mtl-1 mutant strain of Chlamydomonas monoica is unable to protect mt(+)-derived chloroplast DNA. Zygotes homozygous for mtl-1 lose all chloroplast DNA and fail to germinate. We have selected for suppression of this zygote-specific lethality, and have obtained 20 mutant strains that produce viable homozygotes despite the continued presence of the mtl-1 allele. Genetic analysis indicates that the suppressor mutations are all recessive alleles at a single locus (sup-1) which is unlinked to mtl-1. Crosses between sup-1 strains carrying distinctive chloroplast antibiotic resistance markers also show predominantly biparental chloroplast gene transmission. Chloroplast nucleoids of both parental origins (stained with the DNA-specific fluorochrome, DAPI) are retained in the zygotes homozygous for sup 1. The data are compatible with the idea that the sup-1 (suppressor of uniparental inheritance) locus may encode a chloroplast DNA nuclease that is expressed from both parental genomes. PMID- 8005442 TI - A screen for nonconditional dauer-constitutive mutations in Caenorhabditis elegans. AB - In Caenorhabditis elegans, formation of the developmentally arrested dauer larva is induced by high levels of a constitutively secreted pheromone. Synergy between two groups of incompletely penetrant dauer-constitutive (Daf-c) mutations has recently led to a proposal that these two groups of genes are partially redundant and function in two parallel pathways that regulate dauer formation. A possible weakness in this reasoning is that the mutations used to identify the synergy were specifically obtained as incompletely penetrant mutations. Here we use screens to identify new Daf-c alleles without any requirement for partial penetrance. Nevertheless, 22 of the 25 new mutations are incompletely penetrant mutations in 6 previously identified genes. Among these are mutations in daf-8 and daf-19, genes for which only one mutation had been previously identified. Also included in this group are three daf-1 alleles that do not exhibit the maternal rescue characteristic of other daf-1 alleles. Two of the 25 new mutations are fully penetrant and are alleles of daf-2, the one gene in which a fully penetrant mutation had been found earlier. Finally, one of the 25 new mutations is semidominant, temperature-sensitive, and identifies a new gene, daf 28. The results demonstrate that an incompletely penetrant Daf-c phenotype is characteristic of mutations in most Daf-c genes other than daf-2. This finding strengthens the hypothesis that a branched genetic pathway controls dauer formation. PMID- 8005443 TI - A cis-acting locus that promotes crossing over between X chromosomes in Caenorhabditis elegans. AB - This study reports the characterization of a cis-acting locus on the Caenorhabditis elegans X chromosome that is crucial for promoting normal levels of crossing over specifically between the X homologs and for ensuring their proper disjunction at meiosis I. The function of this locus is disrupted by the mutation me8, which maps to the extreme left end of the X chromosome within the region previously implicated by studies of X; A translocations and X duplications to contain a meiotic pairing site. Hermaphrodites homozygous for a deletion of the locus (Df/Df) or heterozygous for a deletion and the me8 mutation (me8/Df) exhibit extremely high level of X chromosome nondisjunction at the reductional division; this is correlated with a sharp decrease in crossing over between the X homologs as evidenced both by reductions in genetic map distances and by the presence of achiasmate chromosomes in cytological preparations of oocyte nuclei. Duplications of the wild-type region that are unlinked to the X chromosome cannot complement the recombination and disjunction defects in trans, indicating that this region must be present in cis to the X chromosome to ensure normal levels of crossing over and proper homolog disjunction. me8 homozygotes exhibit an altered distribution of crossovers along the X chromosome that suggests a defect in processivity along the X chromosome of an event that initiates at the chromosome end. Models are discussed in which the cis-acting locus deleted by the Dfs functions as a meiotic pairing center that recruits trans-acting factors onto the chromosomes to nucleate assembly of a crossover-competent complex between the X homologs. This pairing center might function in the process of homolog recognition, or in the initiation of homologous synapsis. PMID- 8005444 TI - Effects of the maleless mutation on X and autosomal gene expression in Drosophila melanogaster. AB - The mutational effect of the maleless (mle) gene in Drosophila has been reexamined. Earlier work had suggested that mle along with other male-lethal genes was responsible for hypertranscription of the X chromosome in males to bring about dosage compensation. Prompted by studies on dosage sensitive regulatory genes, we tested for effects of mlets on the phenotypes of 16 X or autosomal mutations in adult escapers of lethality. In third instar larvae, prior to the major lethal phase of mle, we examined activities of 6 X or autosomally encoded enzymes, steady state mRNA levels of 15 X-linked or autosomal genes and transcripts from two large genomic segments derived from either the X or from chromosome 2 and present in yeast artificial chromosomes. In contrast to the previously hypothesized role, we detected pronounced effects of mle on the expression of both X-linked and autosomal loci such that a large proportion of the tested genes were increased in expression, while only two X-linked loci were reduced. The most prevalent consequence was an increase of autosomal gene expression, which can explain previously observed reduced X:autosome transcription ratios. These observations suggest that if mle plays a role in the discrimination of the X and the autosomes, it may do so by modification of the effects of dosage sensitive regulatory genes. PMID- 8005445 TI - Synonymous codon usage in Drosophila melanogaster: natural selection and translational accuracy. AB - I present evidence that natural selection biases synonymous codon usage to enhance the accuracy of protein synthesis in Drosophila melanogaster. Since the fitness cost of a translational misincorporation will depend on how the amino acid substitution affects protein function, selection for translational accuracy predicts an association between codon usage in DNA and functional constraint at the protein level. The frequency of preferred codons is significantly higher at codons conserved for amino acids than at nonconserved codons in 38 genes compared between D. melanogaster and Drosophila virilis or Drosophila pseudoobscura (Z = 5.93, P < 10(-6)). Preferred codon usage is also significantly higher in putative zinc-finger and homeodomain regions than in the rest of 28 D. melanogaster transcription factor encoding genes (Z = 8.38, P < 10(-6)). Mutational alternatives (within-gene differences in mutation rates, amino acid changes altering codon preference states, and doublet mutations at adjacent bases) do not appear to explain this association between synonymous codon usage and amino acid constraint. PMID- 8005446 TI - Polygenic mutation in Drosophila melanogaster: estimates from response to selection of inbred strains. AB - Replicated divergent artificial selection for abdominal and sternopleural bristle number from a highly inbred strain of Drosophila melanogaster resulted in an average divergence after 125 generations of selection of 12.0 abdominal and 8.2 sternopleural bristles from the accumulation of new mutations affecting bristle number. Responses to selection were highly asymmetrical, with greater responses for low abdominal and high sternopleural bristle numbers. Estimates of VM, the mutational variance arising per generation, based on the infinitesimal model and averaged over the responses to the first 25 generations of selection, were 4.32 x 10(-3) VE for abdominal bristle number and 3.66 x 10(-3) VE for sternopleural bristle number, where VE is the environmental variance. Based on 10 generations of divergent selection within lines from generation 93, VM for abdominal bristle number was 6.75 x 10(-3) VE and for sternopleural bristle number was 5.31 x 10( 3) VE. However, estimates of VM using the entire 125 generations of response to selection were lower and generally did not fit the infinitesimal model largely because the observed decelerating responses were not compatible with the predicted increasing genetic variance over time. These decelerating responses, periods of response in the opposite direction to artificial selection, and rapid responses to reverse selection all suggest new mutations affecting bristle number on average have deleterious effects on fitness. Commonly observed periods of accelerated responses followed by long periods of stasis suggest a leptokurtic distribution of mutational effects for bristles. PMID- 8005447 TI - Double or nothing: a Drosophila mutation affecting meiotic chromosome segregation in both females and males. AB - We describe a Drosophila mutation, Double or nothing (Dub), that causes meiotic nondisjunction in a conditional, dominant manner. Previously isolated mutations in Drosophila specifically affect meiosis either in females or males, with the exception of the mei-S332 and ord genes which are required for proper sister chromatid cohesion. Dub is unusual in that it causes aberrant chromosome segregation almost exclusively in meiosis I in both sexes. In Dub mutant females both nonexchange and exchange chromosomes undergo nondisjunction, but the effect of Dub on nonexchange chromosomes is more pronounced. Dub reduces recombination levels slightly. Multiple nondisjoined chromosomes frequently cosegregate to the same pole. Dub results in nondisjunction of all chromosomes in meiosis I of males, although the levels are lower than in females. When homozygous, Dub is a conditional lethal allele and exhibits phenotypes consistent with cell death. PMID- 8005448 TI - Cytoplasmic incompatibility in Australian populations of Drosophila melanogaster. AB - In Drosophila melanogaster, weak incompatibility in crosses between infected and uninfected strains is associated with a Wolbachia microorganism. Crosses between infected males and uninfected females show a reduction (15-30%) in egg hatch. Progeny tests indicated that the infection is widespread in Australian D. melanogaster populations and that populations are polymorphic for the presence of the infection. The infection status of 266 lines from 12 populations along the eastern coast of Australia was determined by 4',6-diamidino-2-phenylindole (DAPI) staining of embryos. All populations contained both infected and uninfected flies. Infection frequencies varied between populations but there was no discernible geographical pattern. Laboratory experiments indicated that the infection was not associated with a reduction in fecundity as in Drosophila simulans. Incompatibility levels could not be increased by laboratory selection on isofemale lines. Factors contributing to the persistence of the infection in D. melanogaster populations are discussed. PMID- 8005449 TI - Evaluation of the wheezing infant. AB - Wheezing is a very common symptom or sign in the infant. The evaluation of the underlying cause of the wheezing is difficult and requires a thorough assessment of several factors in the history and physical examination and a basic understanding of the pathophysiology of wheezing. With the increased availability of infant pulmonary function equipment, the evaluation of serial pulmonary function studies in infants with wheezing should prove helpful in continued assessment of the reversibility of their airway obstruction using bronchodilators and the effect of antiinflammatory pharmacologic agents on long-term hyperresponsiveness of the airways. Wheezing-associated respiratory tract infections in infancy ("wheezy bronchitis") and asthma share common risk factors, including history of exposure to environmental tobacco smoke, but the link between these two entities is still controversial. Each infant who presents with wheezing should be assessed individually with a thorough history and physical examination and an evaluation of the likelihood of asthma versus other underlying causes of wheezing such as cystic fibrosis, aspiration syndromes, congenital anomalies, or environmental factors such as exposure to passive tobacco smoking. PMID- 8005450 TI - Imported fire ants: the ants from hell! AB - Imported fire ants may certainly be considered the ANTS FROM HELL! This review focuses on both the interesting entomology of fire ants and the important medical characteristics of fire ant stings. They sting and they kill; they destroy; they mate in mid-air; and we may not be able to stop them. However, although they inject extremely potent venom, individuals can prevent secondary infections by leaving the so-called pustules alone and not opening them. Individuals who suffer systemic reactions may receive adequate treatment with the whole body extract immunotherapy. PMID- 8005451 TI - Latex hypersensitivity: an update. AB - Products containing natural rubber latex can cause both delayed and immediate hypersensitivity. Delayed reactions are induced by chemicals, primarily antidegradants and accelerators, integral to the manufacturing process. Immediate hypersensitivity is caused by protein antigen(s) that occur naturally in the latex. Different manufacturing stages can influence the concentration of these antigens, hence the allergenicity of the final product. The implications of manufacturing and regulatory issues for the diagnosis and treatment of natural rubber latex allergies are therefore discussed. PMID- 8005452 TI - Long-term risk factors for developing asthma and allergic rhinitis: a 23-year follow-up study of college students. AB - In the initial study of 23 years ago, 1836 college freshmen were prospectively evaluated by questionnaires, interviews, and physical examinations for medical conditions which included the presence of asthma, allergic rhinitis, and positive allergy skin tests to a battery of pollens, animal extracts, and mold. In a 23 year follow-up study, 1021 (64%) returned their completed questionnaires. Of these, 738 (72%) had been skin tested as freshmen. The results of this follow-up study revealed that the frequency of asthma and allergic rhinitis continue to increase as the individuals become older. Allergic rhinitis and positive allergy skin tests are significant risk factors for developing new asthma. Individuals with either of these diagnoses are about three times more likely to develop asthma than negative controls. Positive allergy skin tested students have more than twice (2.3x) the risk of developing new hay fever than do negative skin tested students over a 23-year period. PMID- 8005453 TI - The red wine provocation test: intolerance to histamine as a model for food intolerance. AB - Sneezing, flush, headache, diarrhea, skin itch, and shortness of breath are symptoms occurring in patients intolerant to wine after drinking one glass of red wine. The role of histamine in wine intolerance was evaluated by a red wine provocation test in 28 patients with a history of wine intolerance and in 10 controls with good tolerance of wine. Patients were challenged with 125 ml red wine (equivalent to 50 micrograms histamine); blood samples were drawn before and after 15 and 30 minutes. Plasma histamine was assessed by a radioimmunoassay. Lung function tests were performed before and after the wine test. Twenty-two of twenty-eight patients had symptoms showing significantly higher plasma histamine levels 30 minutes after wine challenge (p < .01) compared with asymptomatic controls. Basal histamine levels of patients were higher (p < .05) than in controls. A slight asthmatic attack as well as a 30% decrease of FEF 25 was seen in 2/22 patients. Terfenadine premedication significantly eliminated symptoms in 10/12 patients (p < .05) in a subsequent wine test. Histamine assessment was done in 52 wines (red, white, and champagne) and in 17 beers by radioimmunoassay. Histamine levels ranged from 3-120 micrograms/l in white wines; 15-670 micrograms/l in champagnes; 60-3800 micrograms/l in red wines; and 21-305 micrograms/l in beers. Histamine is causing wine intolerance. Patients intolerant to wine seem to have diminished histamine degradation probably based on a deficiency of diamine oxidase. PMID- 8005454 TI - Lettuce and carrot allergy: are they related? AB - Lettuce is commonly included in many elimination diets of subjects with either food allergy or atopic dermatitis since IgE-mediated allergic reactions have not been reported. We have observed a positive carrot skin test and/or RAST in two clinically lettuce sensitive, ragweed allergic subjects and positive lettuce skin test and/or RAST in two ragweed allergic patients with oral allergy syndrome to carrot. In this study lettuce allergy and the allergenic relationship between iceberg lettuce (Lactuca sativa L.), a member of the Asteraceae and carrot, a member of the Apiaceae, were investigated using sera from those four individuals. SDS-PAGE immunoblotting results indicated that iceberg lettuce can induce an IgE mediated response. Fourteen allergens were detected between 13 and > 113 kD. RAST inhibition demonstrated that carrot does share common allergens with lettuce, although carrot allergens are more potent than those of lettuce. These findings may have some importance in patients with food-related symptoms, such as atopic dermatitis, because lettuce, when included in their diets, may aggravate the underlying disease. PMID- 8005456 TI - Commentary: Spain, Portugal, Christopher Columbus and the Jewish physician. PMID- 8005455 TI - Commentary: prevention and cost of asthma--a model for cost effective health care. PMID- 8005457 TI - Diabetes: 'tight control' in a comprehensive treatment plan. AB - Two out of every five older Americans have abnormal glucose homeostasis. Approximately 1 in 5 has diabetes mellitus, but one-half of these persons are undiagnosed. Treatment of diabetes in older adults is usually managed by primary care physicians. A regular exercise program is the cornerstone of management, even in frail patients. Diet, weight loss, and regular patient education are also important. Age should not limit attempts at tight glucose control in older patients who are cognitively intact and otherwise reasonable candidates. The key to successful management is to follow through with a treatment plan that deals with all of the factors that influence glucose metabolism. PMID- 8005458 TI - Patient restraints: new guidelines for a less restrictive approach. AB - Restraints, both mechanical and pharmacologic, have been overused in hospitals and nursing homes in the United States. Recently, a fundamental change in attitude of the health care team from a paternalistic, institution-centered mode to one that centers on the needs of the patient has led to a less restrictive approach. Typically, restraints have been used to prevent falls or wandering, to control agitation, and to protect medical devices. Before using any form of restraint, however, the physician should consider management alternatives, based on a careful consideration of the patient's problems. PMID- 8005460 TI - Tax check-offs for the NIH? PMID- 8005459 TI - Communication disorders: what to look for, and when to refer. AB - Communication impairments, with or without a swallowing disorder, are common among older adults. Aphasia, which is usually caused by a focal lesion, can affect spoken and written language, auditory comprehension, and reading ability but by itself does not affect intellectual and cognitive abilities. A cognitive communicative impairment is related to underlying cognitive deficits in memory, attention, or visual perception and is seen with traumatic brain injury and nontreatable dementia. Voice and speech impairments such as dysarthria and apraxia of speech may lead to self-imposed social isolation and depression. Dysphagia may accompany a communication disorder or exist independently. As a primary care physician, your in-office workup can help diagnose a communication disorder and identify candidates for referral to an otolaryngologist and/or speech-language pathologist. PMID- 8005461 TI - [Evaluation of risk factors for the deterioration of the state of health in a population effected by environmental conditions]. AB - Method of assessment of ecological and hygienic risk is based on complex assessment of environmental pollution, study of its influence on the state of health taking in view of the prenosologic changes in the body, and determination of causal connections in the system "population-environment". PMID- 8005462 TI - [An adaptation of sanitary and ecologic monitoring to the work conditions of the district center of sanitary and epidemiologic surveillance]. PMID- 8005463 TI - [Rationale for maximum allowable concentration of isobutyl benzoate in atmospheric air of populated areas]. PMID- 8005464 TI - [New method of sanitary protection of water reservoirs]. AB - The causes of inefficacy of water reservoir sanitary protection are considered. Principal issues of a new water protection concept and water quality control are suggested. PMID- 8005465 TI - [Hygienic problems of the protection of water reservoirs in the region of the Baikal-Amur Railway]. PMID- 8005466 TI - [Hygienic rationale for the maximum allowable concentration of ruspol in water reservoirs]. AB - Ruspol is sodium salt of cellulose glycolic acid. Its organoleptic threshold in water is 500 mg/kg. MAC of ruspol in water is recommended on the level 0.5 mg/l. PMID- 8005467 TI - [The problems of occupational hygiene in the manufacturing of nitric acid]. PMID- 8005468 TI - [Rationale for the method of determining the maximum allowable exposure level to hazardous industrial substances adopted in USA]. AB - The comparison of standardization methodology adopted in the USA and in the Russian Federation showed their differences. Nevertheless the use of some methodological elements of USA standardization for RF sanitary legislation may be useful. PMID- 8005469 TI - [Comparative evaluation of morbidity in workers of chemical plants]. AB - The assessment of workers morbidity in production of synthetic detergents and organic synthesis is presented. The levels of morbidity depend of labour conditions, production technology, age of workers. Respiratory infectious diseases occurred at all enterprises. Diseases with involvement of mucous membranes were the most prevalent (rhinitis, rhinopharyngitis, colpitis, and allergic rhinitis). PMID- 8005470 TI - [Assessment of the working conditions of crew members exposed to electromagnetic radiation on river barges]. PMID- 8005471 TI - [Combined effect of the chief chemical elements in the manufacture]. AB - Character of the combined effect of main dust components in working zone air of cermet enterprise is determined. Graphic method for assessment, forecasting and hygienic correction of air quality is suggested. PMID- 8005472 TI - [Health protection of personnel, working with video terminals in passenger service of the railways]. PMID- 8005473 TI - [Dynamic observations of the health status in children in a city with highly developed chemical industry]. PMID- 8005474 TI - [Effect of fibrogenic dust on the organism]. PMID- 8005475 TI - [Work experience with the gamma-radiometer RUG-91 "Adani"]. AB - Some peculiarities of the use of gamma radiometer RUG-91 are analysed. They can be used in practical work and in working out of new apparatuses of "Adani" series. PMID- 8005476 TI - [Ecologic and hygienic safety of housing]. PMID- 8005477 TI - [Physiologic and biogeochemical aspects of pesticide effect on the human body]. PMID- 8005478 TI - [Reaction of biological objects exposed to low-frequency acoustic effects]. PMID- 8005479 TI - [Investigation of fungal contamination of libraries]. PMID- 8005480 TI - [Method of qualitative evaluation of the danger aerosol formation in a microbiological laboratory]. PMID- 8005481 TI - [Use of the programmed algorithm MAH for the analysis of effects of environmental factors on the health of the population]. PMID- 8005483 TI - [Interpretation of hygienic data about chronobiologic toxicity of chemical substances (on the article of A.F.Kovaleva)]. PMID- 8005482 TI - [Method of determining the level of rodanides in biological matter]. PMID- 8005484 TI - [Approaches to integration of hygienic and ecologic standardization]. PMID- 8005485 TI - Protecting the most vulnerable: a proposal to improve Social Security insurance for older women. PMID- 8005486 TI - Home-delivered mental health services: an idea whose time has come? PMID- 8005487 TI - Sharing prosperity across the age distribution: a comparison of the United States and Germany in the 1980s. AB - Using six waves of data from the Panel Study of Income Dynamics and the German Socio-Economic Panel we compare the relative economic well-being of Americans and Germans in the 1980s. Economic growth during the 1980s substantially improved the economic well-being of the average person in the both the United States and Germany. But the rewards were disproportionately distributed across age and gender. In both countries, the family incomes of the very old, the very young and women were lower and grew more slowly than did the income of other families. Social security policy in Germany was more successful than American policy in providing income security in old age. But, despite massive social security programs in both countries, older women were still the most vulnerable members of society, in part because of a substantial drop in the level of social insurance they received following the death of their spouse. PMID- 8005488 TI - The adequacy of Supplemental Security Income benefits for aged individuals and couples. AB - Information is provided on the adequacy of benefits using state-level data on costs and benefits and multiple indicators of adequacy. Maximum Supplemental Security Income (SSI) benefits for aged persons are generally shown to be inadequate. However, when income from other sources is included, couples' SSI benefits appear more adequate when compared to the preferred measures, while those for individuals remain inadequate. Adequacy is also compared across states, and a multivariate analysis is conducted to determine factors that may predict the presence or amount of state supplementary payments. Policy options for improving the adequacy of benefits are discussed. PMID- 8005489 TI - The effect of job mobility on pension wealth. AB - This study examined the extent to which labor market mobility affects workers' ability to amass retirement wealth through employer-sponsored pension plans. This is done by calculating the total pension wealth accumulated over a worker's entire career using different patterns of pension coverage in a variety of jobs. The study indicates that, with a mobile workforce, accumulation of pension wealth depends critically on the type and timing of pension coverage during a career. PMID- 8005490 TI - Therapy termination and persistence patterns of elderly clients in a community mental health center. AB - Analyses were conducted on 180 community and nursing home clients, ages 60 to 98, who received psychotherapy as part of a community mental health center program. Case records were reviewed to identify factors associated with persistence in therapy and dropout patterns. Very few (less than 12%) terminated therapy appropriately (as judged by the therapist), about 59% completed at least 10 sessions, and a majority of the community residents themselves initiated termination. Persistence in treatment was associated with nursing home residence, religious beliefs, and receiving the therapy at home. Contrary to predictions, persistence was not associated with self-referral, type of psychiatric diagnosis, age, or gender. PMID- 8005491 TI - Long-term care service use by frail elders: is ethnicity a factor? AB - Using data from the 1982-84 National Long-Term Care Channeling Demonstration, this study examines factors associated with long-term care service use by African American, Hispanic, and white frail elders living in the community. Findings indicate that in addition to predisposing, enabling, and need factors, race/ethnicity is a significant predictor of each type of service use. PMID- 8005493 TI - Grandparents who parent their grandchildren: circumstances and decisions. AB - This research is based on in-depth interviews with 114 grandparents who responded to advertisements that appeared in the media, schools, and courts. Three major categories of grandparent roles emerged from the data: custodial, living with the grandchild, and day-care roles. At one end of the continuum of care, custodial grandparents often obtain that relationship because of severe problems in the nuclear family. At the other end, day-care grandparents provide regular help to the grandchild's nuclear family. The decision to provide care is often based on an "impulse to care," especially among custodial and living-with grandparents. Grandparents who provide regular day care to grandchildren generally have offered to do so. PMID- 8005492 TI - The costs of family contributions to the care of persons with dementia. AB - This study focuses on the costs of dementia care incurred by families. Cost components operationalized include: costs of unpaid caregiver labor services, paid and unpaid family labor, paid and unpaid services of nonfamily persons, and cash outlays for equipment and services. Among 182 families of dementia patients, average care costs for a 3-month period amount to $4,564. Cash expenditures average only 29% of total care costs, with unpaid labor accounting for 71% of the family care costs. Total care costs rise by $1,158 for each additional dependency in an activity of daily living (ADL), while reliance on paid services is 5% higher for each additional $10,000 household income and drops by 25% if the patient lives in the caregiver's household. PMID- 8005494 TI - Dependency status and happiness with old age on Java. AB - Using data from a survey of elderly persons on Java, we investigate the prevalence of dependency states (functional, economic, and residential) and the implications of dependency status for happiness with old age. Whereas being dependent is common in the later years, many older persons still have dependents. Dependency on kin is not a negative situation in this context, but having economic dependents appears to be burdensome. Gender, being able to provide an inheritance, and rural-urban residence moderate the relationship between dependency status and happiness. PMID- 8005495 TI - Salient themes in the life review of a sample of frail elderly respondents in London. AB - Over the past 20 years increasing attention has been paid to women's experience of their lives, in the context of the life review (Wallace, 1992) and the whole general process of account making (Weber, 1992). However, there has been an implicit expectation that feelings of loss will be "resolved" (Wortman & Silver, 1989). Drawing on material from 134 in-depth interviews with frail elderly Social Service Department clients in North London, this article questions this idea by illustrating the salience of loss in their life review. PMID- 8005497 TI - Sharing the caring: family caregivers' views of their relationships with nursing home staff. AB - Using data from focus groups and individual interviews with family caregivers who had a spouse or a parent with Alzheimer's disease, we examined their reports of interactions with staff in formal care settings. Families most often discussed nurses' aides; they emphasized their desire for an ongoing relationship with staff members; and, they interpreted staff behaviors in terms of high-quality care that was based on the social and emotional care given to their resident as much as on the technical tasks involved in caring for them. These results point to the families' desire for emotionally sensitive care and not just for technically competent performance of tasks. PMID- 8005496 TI - Assessment of depression in dementia patients: association of caregiver mood with depression ratings. AB - Caregivers typically provide critical diagnostic information on patients with dementia and possible depression. Yet, their accuracy and the potential influence of their own mood on assessment is unknown. In this study, caregivers rated a standardized stimulus of depression and their actual patient. They were able to correctly identify depression in both. Further, their mood was unassociated with video ratings and only moderately associated with patient ratings. Thus, reliance on caregiver input is supported. PMID- 8005498 TI - Nursing home aides: saints or monsters? AB - In-depth fieldwork in a New York City nursing home shows that most aides were neither saints nor monsters. Only a small minority were consistently cruel, on the one hand, or consistently warm and supportive, on the other. While there were many instances of harsh treatment of patients, most nursing aides were kind and helpful to residents most of the time. Indeed, many aides established relations with patients that they and the patients found gratifying. PMID- 8005499 TI - Dementia: not just a search for the gene. AB - We extend the reasoning commonly applied to the understanding of chronic diseases and their prevention to Alzheimer's disease and other dementing disorders. The highly visible progress in finding genetic bases of Alzheimer's disease may leave a large proportion of cases unexplained. Rather, both genetic susceptibility and environmental factors are demonstrably important for disease expression. Thus, the research and health policy implication would be to target resources toward identifying and modifying environmental risk factors that might delay or prevent dementia. PMID- 8005500 TI - A linkage of knowledge and attitudes toward elderly sexuality: not necessarily a uniform relationship. AB - A critical review of the literature regarding individuals' knowledge and their attitudes toward elderly sexuality is presented. A generally positive relationship was discovered between various age cohorts' depth of knowledge and their permissiveness of attitudes. However, some health care providers demonstrated a negative relationship between their knowledge and attitudes. In future studies, the use of a moderator methodology, rather than seeking a uniform relationship, appears essential in order to understand discrepant findings. PMID- 8005501 TI - Coming together for change: workshops for women in the nursing home. AB - A series of therapeutic and educational workshops were conducted with women nursing home residents with the twin goals of improving self-esteem and self reliance, and facilitating community building and networking. Alongside these workshops were nursing home staff trainings whereby staff were encouraged to articulate their needs and those of resident women in productive ways. PMID- 8005502 TI - LIFE: Learning Informally From Elders. AB - The Better Elder Services Today (BEST) Project helps frail elders maintain healthy, independent living through partnership with their formal and informal caregivers. This article reports on achieving one particular project goal: the development of community forums in which elders engaged in problem-solving with health care professionals and policy makers. The methodology involved community assessment and qualitative analysis of themes in 102 elders' responses to the question, "What has it been like for you trying to remain as independent as possible in the community?" Five predominant themes emerged: safety; problems communicating with health care providers; dissatisfaction with hospital services; complexity in access to community services; and fears about losses. PMID- 8005503 TI - [Correlation between the time of application of chorionic gonadotropins and biological variables in the gametes]. AB - The scheduled administration of human chorionic gonadotropin in the ovarian stimulation schemes used in Assisted reproduction has made possible to control the ovulatory phenomenon. In order to know the biological repercussion upon the ovule as to elapsed time from HCG and the time of capture, the protocols of Gametes Laboratory, were reviewed; there were 277 cases with this factor. The capture moment was from 32.88 to 41.06 hours from HCG administration, with an average of 36.8 +/- 1.01 hours. There was no significant statistical correlation with the total amount of captured oocytes, useful oocytes, defective oocytes (atresic, broken, degenerated) segmentation rate and embryonary quality. There was a positive, lineal, statistical correlation with the amount of post-mature oocytes (r = 0.35, p = 0.019) and negative with fertilization rate (r = -0.30, p = < 0.0001), both without a correlation among themselves. It was concluded that prolonged time between HCG exposition more than difficulting oocyte capture, negatively affects oocyte quality with a diminution in its possibility of being fertilized. It must be found the optimal window that permits easily obtaining the larger amount of oocytes with the best possibilities of originating healthy pre embryos. PMID- 8005504 TI - [Chemotactic factor for spermatozoa: a new biological function of progesterone]. AB - Our group has recently described the existence of a chemoattractant factor for spermatozoa contained in the mature follicles fluid. Simultaneously it was possible to develop a new method that permits to evaluate the chemotactic capacity of spermatozoa and that due to its simplicity makes possible the systematic study of CFS features. This study considered CFS molecular characterization from follicular fluid (FF). The FF of women was studied in an Assisted Fertilization Program, that were qualified as mature according to different criteria. The FF were fractioned with different techniques that permitted to separate an active fraction with lipid physicochemical characteristics. The fine layer chromatography showed the presence of different steroids, that were individually assayed for chemotactic activity. Only progesterone showed that activity and its effect showed a dose-response curve within physiological values. Our study permitted to identify progesterone as CFS previously described. This steroid's function is rather new and its action mechanism is being studied in our laboratory. PMID- 8005505 TI - [Value of the amniotic fluid rate in premature membrane rupture: prognosis of infection]. AB - The presence of oligohydramnios evaluated by accumulation or major pool technique in pre-term PMR is strongly correlated with maternal and perinatal infection. The objective of this study is to evaluate the usefulness of amniotic fluid volume rate (AFVR) in prediction of maternal and fetal-neonatal infection in patients with PMR before 37 weeks. Thirty patients with PMR were prospectively studied. AFVR was done in all the patients at the time of arrival and they were managed conservatively. None of them had utero-inhibitors and only antibiotics were used after chord clamping. In absence of intrauterine infection corticotherapy was allowed. The results of AFVR were correlated with maternal infection (chorioamnioitis) and perinatal (possible neonatal sepsis or neonatal sepsis). Twenty three out of 30 patients (76.6%) had a AFVR less than or equal to 5.0 cm. (Oligohydramnios) and seven (30.4%) showed a greater rate than 5.0 cm. The earliest pregnancy was 26.5 weeks and the greatest 34.4 weeks. Out of the total of patients 13 (43.3%) had chorioamnioitis and all correspond to the group with AFVI smaller or equal to 5.0 cm. In the group with oligohydramnios were 15 neonates (65.2%) with neonatal infection (six possible sepsis and nine neonatal sepsis). All neonates with positive cultures also corresponded to the group with smaller AFVR; the comparison among the cases with oligohydramnios with infection and the ones that had normal AFVR without infection has statistical significance (p = 0.01).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8005506 TI - [Ultrastructural study of placentas from HIV seropositive women]. AB - Eleven placentas from seropositive women for HIV, were analyzed. In three cases the material came from first trimester abortions and the other eight from term pregnancies. In five cases retroviruses were identified, similar to HIV in the placental tissue. It was demonstrated for the first time the internalization of a retrovirus and its presence in the syncytiotrophoblast. It is communicated for the first time the presence of one cell in the placental stroma different to Hofbauer's by its granules type. PMID- 8005507 TI - [Phospholipase A2 and premature membrane rupture]. AB - The phospholipase A2 activity in young amniotic fluids: 1.782, was determined. In the term amniotic fluids, the activity was 10.693. The detected activity in fluids from premature rupture of membranes was 29.077 in the group with infection, add 12.357 for the samples without infection. It was seen that young amniotic fluid has less activity. The group with infection showed the greatest activity. The significant increase of phospholipase A2 activity in term amniotic fluids and with PRM, in comparison with what is seen in young fluids suggests the active participation of the soluble form of this enzyme as mediator in the increase of Prostaglandin E2 seen in the amniotic fluid of the two first groups. Accordingly, one may think that PPLA2 could be a central mediator in membranes rupture mechanism in normal labor, as in PRM. PMID- 8005508 TI - [Symptoms in adolescents in two Mexican cities and association with the menstrual cycle]. AB - Frequency an severity of physical and emotional symptoms in young female students from two cities of Mexico (a medium and a large sized city), were studied. An interview was carried out in 447 female adolescents, non seeking treatment, in a cross sectional design (146 from Guadalajara, and 301 from Leon). The mean age was 16.7 years (16.5 + SD 1.7 and 17.1 +/- 1.9 respectively). Most frequent symptoms for both groups were abdominal bloating, acne, increased appetite, low back pain, polydipsia, and emotional symptoms related to depression such as fatigue, desire to stay at home, desire to be alone and anxiety. Adolescents from Guadalajara reported increased intensity of diverse symptoms in comparison with adolescents from Leon: Breast tenderness, polydipsia and symptoms of depression. Difference was maintained after adjustment for covariates. In regards to the phase of the menstrual cycle, significantly different symptoms were: Abdominal bloating, breast tenderness, constipation, pruritus, lack of concentration, lack of coordination and symptoms of depression. It is concluded that female adolescents report increased scores on several physical and emotional symptoms during the menstrual phase of the cycle. Women from large urban populations report symptoms with increased intensity. PMID- 8005509 TI - Peroxidation of human blood lipoproteins induced by exogenous hypochlorite or hypochlorite generated in the system of "myeloperoxidase + H2O2 + Cl-". AB - Oxidation of human plasma lipoprotein (LP) was studied in the presence of exogenous hypochlorite anion (OCl-) or OCl- generated in the "myeloperoxidase + H2O2 + Cl-" system. OCl- effectively initiates peroxidation of lipids extracted from LP and those within LP particles, as can be judged from accumulation of secondary (thiobarbituric acid [TBA] reactive) and final (Schiff bases) products of lipid peroxidation (LPO) in LP after incubation with myeloperoxidase or exogenous OCl-. Very low density and low density lipoproteins classified as atherogenic LP are more sensitive to OCl(-)-induced LPO than high density lipoproteins. These data allow us to propose that OCl- secreted by activated neutrophils and monocyte-macrophages can produce oxidative modification of LP in vivo. The latter is known as a risk factor in the development of atherosclerosis. PMID- 8005510 TI - Peroxynitrite-mediated oxidation of dihydrorhodamine 123. AB - Nitric oxide reacts with superoxide to form peroxynitrite, which may be an important mediator of free radical-induced cellular injury. Oxidation of dihydrorhodamine to fluorescent rhodamine is a marker of cellular oxidant production. We investigated the mechanisms of peroxynitrite-mediated formation of rhodamine from dihydrorhodamine. Peroxynitrite at low levels (0-1000 nM) induced a linear, concentration-dependent, oxidation of dihydrorhodamine. Hydroxyl radical scavengers mannitol and dimethylsulfoxide had minimal effect (< 10%) on rhodamine production. Peroxynitrite-mediated formation of rhodamine was not dependent on metal ion catalyzed reactions because studies were performed in metal ion-free buffer and rhodamine formation was not enhanced in the presence of Fe3+ ethylenediaminetetraacetic acid (EDTA). Thus, rhodamine formation appears to be mediated directly by peroxynitrite. Superoxide dismutase slightly enhanced rhodamine production. L-cysteine was an efficient inhibitor (KI approximately 25 microM) of dihydrorhodamine oxidation through competetive oxidation of free sulfhydryls. Urate was also an efficient inhibitor (KI approximately 2.5 microM), possibly by reduction of an intermediate dihydrorhodamine radical and recycling of dihydrorhodamine. Under anaerobic conditions, nitric oxide did not oxidize dihydrorhodamine and inhibited spontaneous oxidation of dihydrorhodamine. In the presence of oxygen, nitric oxide induces a relatively slow oxidation of dihydrorhodamine due to the formation of nitrogen dioxide. We conclude that dihydrorhodamine is a sensitive and efficient trap for peroxynitrite and may serve as a probe for peroxynitrite production. PMID- 8005511 TI - Effect of reactive oxygen species on the biosynthesis and structure of newly synthesized proteoglycans. AB - The effect of reactive oxygen species (ROS) generated by a xanthine oxidase hypoxanthine system (mainly H2O2) on proteoglycan (PG) metabolism and structure was investigated in vitro, using cell monolayers of cultured rabbit articular chondrocytes and purified resident and newly synthesized proteoglycans. It was shown that ROS generated in this system frequently stimulate (at low concentrations), and consistently inhibit (at higher concentrations), the incorporation of 35SO4 and 3H-glucosamine into PG molecules synthesized by cultured chondrocytes. The inhibition of isotopes' incorporation at higher enzyme concentrations was suppressed completely by heating xanthine oxidase and allopurinol with superoxide dismutase (SOD) and catalase. ROS at high concentration also inhibited 3H-uridine incorporation but had no effect on 35SO4 and 3H-uridine uptake by the cells. They also alter hyaluronan (HA) and PG monomers by fragmenting the core protein moiety and destroying the hyaluronic acid binding region. Altered PG monomers do not interact with HA to form complexes, but fragmented HA still retain a significant PG monomer-binding capacity. PG-HA complexes are easily and irreversibly destroyed by ROS. These results suggest that ROS may at low fluxes stimulate PG-synthesis under physiological conditions and alter cartilage metabolism and structure in conditions where they are overproduced, such as in rheumatoid arthritis, and in hemochromatosis and other iron storage diseases. PMID- 8005512 TI - Cytotoxicity of oxidants and asbestos fibers in cultured human mesothelial cells. AB - The authors investigated the mechanisms caused by oxidants (superoxide and hydrogen peroxide) and asbestos (amosite) fibers in human mesothelial cells. Immortalized human pleural mesothelial cells (MET 5A) were exposed in vitro to one of the following: hypoxanthine (100-200 microM) plus xanthine oxidase (10-20 mU/ml) as a superoxide-generating system, H2O2 (50 microM-5 mM); or amosite (1 100 micrograms/cm2). Cellular adenine nucleotide depletion, DNA single strand breaks, extracellular release of nucleotides, and their catabolites and lactate dehydrogenase (LDH) were assessed as markers of cell damage after 4-6 h exposure to the oxidants or fibers. The effect of intracellular antioxidant enzymes and exogenous antioxidants on cell damage were investigated during oxidant and amosite exposure. Superoxide radical and H2O2 exposure resulted in the depletion of adenine nucleotides, accumulation of the products of nucleotide catabolism, induction of DNA single strand breaks, and extracellular LDH release. Amosite exposure did not cause nucleotide depletion or induction of DNA single strand breaks. Inactivation of the intracellular antioxidant enzymes glutathione reductase or catalase augmented cell damage during H2O2 exposure but not during amosite exposure. PMID- 8005513 TI - New roles for quin2: powerful transition-metal ion chelator that inhibits copper , but potentiates iron-driven, Fenton-type reactions. AB - The objective of this study was to investigate whether quin2, through its metal chelating properties, could affect copper- or iron-driven Fenton reactions. Chelation of ferric ion with quin2 uniformly strongly enhanced the formation of oxidizing species, detected with the DMSO and deoxyribose assays, both by H2O2 and a mixture of superoxide/hydrogen peroxide produced by hypoxanthine/xanthine oxidase. Fe(3+)-EDTA gave the same effects, but lacked reactivity with bolus H2O2 as detected with the DMSO assay. Whereas the formation of oxidizing species with Fe(3+)-EDTA and ferric ions alone were strongly inhibited by superoxide dismutase both in the bolus H2O2 and hypoxanthine/xanthine oxidase systems, such formation in the presence of Fe(3+)-quin2 either did not decrease or decreased only moderately. Fe(3+)-quin2 also strongly enhanced plasmid DNA strand breakage in the presence of H2O2. Our findings suggest that quin2 as chelator of ferric ion may be a more powerful enhancer of oxidant formation than other chelators so far tested. The formation of oxidizing species from copper ions and bolus H2O2 was found to be fundamentally dependent on the choice of buffer system. We could only detect significant amounts of oxidants in both assays in Hepes buffer, but not in the phosphate, cacodylate or unbuffered systems, which all gave low reactivity in the DMSO assay compared to the deoxyribose assay. Quin2 chelation of cupric ion effectively inhibited the formation of oxidants as well as plasmid DNA strand breakage.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8005514 TI - The toxicity of high-dose superoxide dismutase suggests that superoxide can both initiate and terminate lipid peroxidation in the reperfused heart. AB - Recently, we described an anomalous bell-shaped dose-response curve for the protection of the reoxygenated isolated myocardium by superoxide dismutase (SOD). SOD is dramatically protective up to a point (5 micrograms/ml in the perfusate) beyond which it loses its ability to protect and, at very high doses (50 micrograms/ml), exacerbates the injury. We proposed that O2-. may serve as both initiator and terminator of lipid peroxidation, such that over scavenging the radical may increase net lipid peroxidation via increased chain length. We examined the ability of U74389F, a lipid peroxidation inhibitor, to ameliorate the toxicity of high-dose SOD in the isolated perfused rabbit heart preparation. The results show a significant improvement in the percent recovery of developed tension of hearts treated with U74389F and overdosed with MnSOD, as well as a decrease in thiobarbituric acid reactive substances. PMID- 8005515 TI - Probucol scavenged 1,1-diphenyl-2-picrylhydrazyl radicals and inhibited formation of thiobarbituric acid reactive substances. AB - Probucol is suggested to have antioxidant properties. The direct scavenging action of probucol on hydroxyl radicals, superoxide and 1,1-diphenyl-2 picrylhydrazyl (DPPH) radicals were examined using electron spin resonance (ESR) spectrometry. Probucol scavenged DPPH radicals dose dependently but showed no effect on hydroxyl radicals and superoxide generated by Fenton reaction and by hypoxanthine-xanthine oxidase system, respectively. It inhibited the formation of thiobarbituric acid reactive substances (TBARS) in rat cortex homogenate induced by ascorbic acid and FeCl2 at low dose, but it increased TBARS formation at high doses. Probucol showed no effect on the carbon centered radicals. Iron injection into the rat cortex, which is an experimental model for traumatic epilepsy, increased TBARS level in the cortex, hippocampus, striatum and cerebellum, but pretreatment with probucol inhibited the increase in these brain parts except for the hippocampus. These results suggest that the antioxidant property of probucol is partly due to its free radical scavenging effect. PMID- 8005516 TI - Age-dependent increase of mitochondrial DNA deletions together with lipid peroxides and superoxide dismutase in human liver mitochondria. AB - We previously reported an age-dependent deterioration of mitochondrial respiration as well as two age-associated mitochondrial DNA (mtDNA) deletions in the human liver. In this study, we further determined the relative quantities of the deleted mtDNAs in liver biopsies from 64 subjects of different ages. The results showed that both mtDNA deletions increase in frequency and quantity with age. Moreover, we measured hepatic lipid peroxides (malondialdehyde; MDA) of isolated mitochondria and manganese superoxide dismutase (Mn-SOD) activity of submitochondrial particles. We found a significant age-dependent increase in both MDA and Mn-SOD levels in liver mitochondria. These results confirm the previous contention that enhanced generation of lipid peroxides in the mitochondria during the aging process may damage mtDNA, and mtDNA deletions may be one of the important factors contributing to aging in humans. PMID- 8005517 TI - The roles of ascorbic acid and other antioxidants in the erythrocyte in reducing membrane nitroxide radicals. AB - Fatty acid nitroxide radicals in CO-gassed erythrocytes are reduced by intracellular components with a half-life of about 160 min. In this study, using reduction rate constants of fatty acid spin labels to determine the reduction quantitatively, we found that catalase, glutathione, glutathione peroxidase, superoxide dismutase, and vitamin E--as well as hemoglobin, individually or in concerted manner, contributed little in reducing membrane nitroxides. Ascorbic acid appeared to be the predominant component in the erythrocyte to reduce membrane nitroxides. However, ascorbic acid solutions at 0.1 mM or less, concentrations similar to those found in the erythrocyte, produced no observable reduction in spin labeled membranes during the 2 h monitoring period. Ascorbic acid solutions at about 1 mM were needed to exhibit rate constants similar to those observed in labeled erythrocyte samples. It was also found that beta nicotinamide adenine dinucleotide, beta-nicotinamide adenine dinucleotide phosphate, and heat-sensitive components in the erythrocyte enhanced the ability of ascorbic acid to scavenge nitroxide radicals in the erythrocyte membrane near the membrane surface. PMID- 8005518 TI - Plasma lipid peroxidation in critically ill patients: importance of mechanical ventilation. AB - Oxygen free radicals may be implicated in the pathogenesis of both ischemia reperfusion damage and in circulatory shock. The attack on the cell membrane by free radicals leads to lipid peroxidation, which can be assessed by the plasma malondialdehyde (MDA) level. The aim of this study was to determine the importance of lipid peroxidation in critically ill patients. The MDA level was measured by the thiobarbituric acid test. Nineteen patients at an early stage of circulatory shock, 11 patients in the weaning period of ventilation, 9 gastro enterological patients without cardio-circulatory distress or sepsis, and 9 healthy volunteers were studied. The MDA level was higher in critically ill patients than in control subjects (61% in patients with shock and 40% in patients on mechanical ventilation). No correlation was found between the MDA level and the outcome: multiple organ failure or acute respiratory distress syndrome. This proposal leads to the question of systematic antioxidant therapy in intensive care patients. PMID- 8005519 TI - Determinants of plasma vitamin E concentrations. AB - Vitamin E, a lipid soluble antioxidant, is transported in plasma lipoproteins. This review will summarize the mechanisms for the preferential incorporation of RRR-alpha-tocopherol into lipoproteins. Special attention is devoted to the hepatic tocopherol binding protein, and to patients who are vitamin E deficient because they apparently have a genetic defect in this protein. The regulation of plasma vitamin E by the tocopherol binding protein as a determinant of the biologic activity of various forms of vitamin E is also discussed. PMID- 8005520 TI - Regio- and stereochemistry of the dioxygenation reaction catalyzed by (S)-type lipoxygenases or by the cyclooxygenase activity of prostaglandin H synthases. AB - Investigations on the regio- and stereochemistry of the reactions of mammalian lipoxygenases and of prostaglandin H synthases are reviewed. The results and concepts are summarized as two reaction box models. The structures of all known (S)-type lipoxygenase products of long-chain fatty acids carrying an all-cis-1,4 diene structural element including mono-, di-, and tri-hydroxyl products can be accommodated by this model. The model also provides an explanation for leukotriene formation by mammalian lipoxygenases and for the substrate specificity of lipoxygenases towards esterified fatty acids. The reaction box model for the first dioxygenation step of the cyclooxygenase activity of prostaglandin H synthase is stereochemically different from the (S)-type lipoxygenase box model. PMID- 8005521 TI - Oxidative injury in reoxygenated and reperfused hearts. AB - In this study, we separated the effects of low oxygen supply and low coronary flow in isolated perfused rat hearts to focus on the genesis of free radicals induced reperfusion injury. Hearts were exposed to either hypoxemia/reoxygenation or ischemia/reperfusion in various sequences, with hypoxemia and ischemia matched for duration (20 min), temperature (37 degrees C), and oxygen supply (10% of baseline). Hypoxemia/reoxygenation (n = 7) resulted in lower (developed pressure) x (heart rate) (p < 0.001) and higher end-diastolic pressure (p < 0.001) than ischemia/reperfusion (n = 9). The presence of 40 IU/ml superoxide dismutase and 104 IU/ml catalase nearly blunted the rise of the end-diastolic pressure (p = 0.02 vs. baseline), but could only partially prevent the depression of myocardial contractility (p < 0.001 vs. baseline, n = 7). Similar patterns were observed when hearts were made ischemic after hypoxemia, eliminating the intermediate reoxygenation step. We conclude that the major determinant of the reperfusion injury is associated with low oxygen supply rather than low coronary flow. Part of the injury is mediated by oxygen-derived free radicals, but a substantial portion of it is associated with energetic processes. PMID- 8005522 TI - Ethanol synergizes with hydrogen peroxide, peroxyl radical, and trypsin to kill epithelial cells in culture. AB - Monkey kidney epithelial cells, labeled with chromium and grown in culture, were killed in a synergistic manner when subtoxic amounts of ethanol were combined either with subtoxic amounts of glucose oxidase-generated hydrogen peroxide, or with mixtures of peroxide and with 2,2'-Azo-bis (2-amidinopropane)HCl (AAPH) generated peroxyl radical. A further enhancement of cytotoxicity occurred when subtoxic amounts of trypsin were added to mixtures of all three agents. While ethanol alone caused shrinkage of the monolayers and cell rounding, no visible cytotoxic changes were observed. Hydrogen peroxide at the concentrations used (about 1 mM), caused only some cell rounding. On the other hand, cells exposed simultaneously to ethanol and to H2O2 developed extensive membrane damage characterized by the formation of large polar blebs, which is compatible with altered membrane permeability. The presence of trypsin markedly enhanced cellular cytotoxicity induced by mixtures of peroxide, peroxyl radical, and ethanol. This could markedly be depressed by catalase and by dimethylthiourea. The tissue culture model described might serve to further investigate the role played by synergy among oxidants and a variety of membrane-damaging agents, and by xenobiotics in tissue damage induced by inflammatory processes. PMID- 8005523 TI - DNA damage in the kidneys of diabetic rats exhibiting microalbuminuria. AB - 8-Hydroxydeoxyguanosine (8-OHdG), an oxygen radical induced modification of purine residue in DNA, was measured in the liver, pancreas, and kidney of streptozotocin-induced diabetic rats (STZR) exhibiting microalbuminuria. At 4 weeks after the injection of streptozotocin (50 mg/kg, i.v.), the rate of urinary albumin excretion was 0.5 +/- 0.1 and 2.0 +/- 0.2 mg/24 h in age-matched control rats (CR) and STZR, respectively. Compared to CR, STZR also showed a significantly increased level of 8-OHdG in the kidney but not the liver and pancreas. Amounts of 8-OHdG/10(5) dG for CR and STZR were 3.4 +/- 0.3 and 5.1 +/- 0.2 for renal cortices, and 4.1 +/- 0.2 and 20.0 +/- 3.7 for renal papillae. Daily injection of insulin (2 U, SC) starting on the third day after streptozotocin treatment significantly reduced both urinary albumin excretion and papillary 8-OHdG formation, which suggests that these are associated with the diabetic state induced by streptozotocin rather than a direct nephrotoxic effect of the drug. This study suggests that formation of 8-OHdG and, therefore, oxidative damage are closely related in the process of diabetic nephropathy. PMID- 8005524 TI - Protective effect of dietary selenium supplementation on delayed cardiotoxicity of adriamycin in rat: is PHGPX but not GPX involved? AB - The involvement of Se enzymes in the protection against the oxidative stress induced by adriamycin (ADR) in rat heart has been studied in animals fed for 10 weeks at three different levels of Se content (low = 0.02 ppm; normal = 0.5 ppm; high = 1.0 ppm) and receiving a weekly injection of 3 mg/kg ADR for 4 weeks. ECG (QaT duration) and contractility of isolated atria were measured. The high-Se diet showed a significant protection on both parameters. To assess the hypothesis that an increase of specific activity of antioxidant Se enzymes may account for the cardioprotective effect of selenium, glutathione peroxidase (GPX), and phospholipid hydroperoxide glutathione peroxidase (PHGPX) were tested. The assays were performed on ventricles isolated from treated rats. At the end of the experimental period, GPX (cytosolic enzyme) did not show any significant difference between controls and ADR-treated at any level of Se content, thus excluding its involvement in the cardioprotection observed in high-Se ADR-treated animals. PHGPX, which is present both in cytosol and in the cell membrane, showed a trend to increase its activity in the presence of ADR treatment only in the membrane fraction; however, the statistical significance was reached only in the low-Se group (+100%). This observation suggests that membrane PHGPX might be involved in the cellular mechanism of adaptation of the heart to the toxic effects of ADR; however, the behavior of these enzymes does not seem to account for the significant protection of selenium supplementation both on ECG and on contractile indices of ADR cardiotoxicity.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8005525 TI - The hazard of hydroxyl radicals: response to comments of W. H. Koppenol and Z. Maskos. PMID- 8005527 TI - Reduction of myocardial infarct size in rat by IRFI-048, a selective analogue of vitamin E. AB - The effects of IRFI-048 (2,3-dihydro-5-methoxy-4,6,7-trimethyl-2-benzofuranyl acetic acid), a selective analogue of Vitamin E, on myocardial tissue injury were examined in anaesthetized rats subjected to 60-min occlusion of the left coronary artery followed by 60-min reperfusion. Infarct size (Evan's blue and tetrazolium stain), serum creatinphosphokinase (CPK), plasma malonaldehyde (MAL), cardiac myeloperoxidase (MPO) activity, and ST-segment of electrocardiogram (ECG) and survival rate were evaluated. Postischaemic reperfusion produced severe cardiac necrosis, caused neutrophil (PMNs) infiltration (evaluated by MPO activity) in the jeopardized tissue, increased serum CPK and plasma MAL, raised ST-segment of ECG, and decreased survival rate. IRFI-048, (200 and 400 mg/kg o.s.) given to the rats 6 h before occlusion, caused a reduction of necrotic area expressed as a percentage of either the area at risk or the total left ventricle, decreased MPO activity both in the area at risk (from 3.2 +/- 0.3 U x 10(-3)/g tissue to 1.1 +/ 0.4 U x 10(-3)/g tissue; p < .005) and in the necrotic area (from 5.7 +/- 0.9 U x 10(-3)/g tissue to 1.8 +/- 0.5 U x 10(-3)/g tissue; p < .001), attenuated the rise of ST-segment of ECG (from 0.51 +/- 0.14 mV in the vehicle group to 0.28 +/- 0.11 mV in the treated group; p < .005), reduced the increase of plasma MAL and serum CPK during reperfusion (from 42 +/- 5.3 nmol/ml to 15 +/- 3.1 nmol/ml and 139 +/- 13 IU/100 ml to 58 +/- 7.5 IU/100 ml, respectively; p < .001).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8005526 TI - Ascorbate protects guinea pig tissues against lipid peroxidation. AB - In recent years we and others have shown that ascorbic acid (AH2) is a potential scavenger of superoxide (O2.-) and peroxyl (LOO.) radicals, the species involved in lipid peroxidation (LPO) in animal tissues. In this paper we have demonstrated that AH2 protects guinea pig tissues from LPO both in vivo and in vitro. The extent of LPO has been determined by estimating malonaldehyde using the thiobarbituric acid test and HPLC and also by measuring the accumulation of fluorescent pigment and occurrence of protein changes in the microsomal membranes. In AH2-deficiency, LPO occurs progressively in guinea pig tissues, despite the presence of adequate levels of antioxidants like alpha-tocopherol, GSH, protein thiols, and scavenging enzymes, namely, superoxide dismutase, catalase, and glutathione peroxidase. In a model in vitro system, microsomal LPO initiated by O2.- is completely prevented by AH2 but not by alpha-tocopherol, GSH, uric acid, and catalase. AH2 is also the most effective antioxidant in preventing microsomal LPO mediated by tert-butylhydroperoxide or the chain propagating species LOO., generated from 2,2'-azobis (2-amidinopropane) hydrochloride. The results obtained with guinea pigs may be applicable to humans, because humans are also dependent on dietary AH2. Our data suggest that an adequate vitamin C nutrition may prevent common cellular degenerative diseases associated with LPO. PMID- 8005528 TI - Protection by vitamin E selenium, trolox C, ascorbic acid palmitate, acetylcysteine, coenzyme Q, beta-carotene, canthaxanthin, and (+)-catechin against oxidative damage to liver slices measured by oxidized heme proteins. AB - Male SD rats were fed a vitamin E- and selenium-deficient diet, a diet supplemented with vitamin E and selenium, and diets supplemented with vitamin E, selenium, trolox C, ascorbic acid palmitate, acetylcysteine, beta-carotene, canthaxanthin, coenzyme Q0, coenzyme Q10, and (+)-catechin. Liver slices were incubated at 37 degrees C with and without CBrCl3, t-butyl-hydroperoxide, Fe+2, or Cu+2. The effect of antioxidant nutrients on the oxidative damage to rat liver was studied by measurement of the production of oxidized heme proteins (OHP) during the oxidative reactions. Diet supplemented with vitamin E and selenium showed a strong protection against heme protein oxidation compared to the antioxidant-deficient diet. Furthermore, increasing the diversity and quantity of antioxidants in the diets provided significantly more protection. PMID- 8005529 TI - Oxidative stress in muscle and liver of rats with septic syndrome. AB - Sepsis, as infection associated to systemic manifestations, was produced in rats by cecal ligation and double perforation. Sham-operated rats were used as controls. The spontaneous chemiluminescence of rat adductor muscle and liver were measured at 6, 12, 24, and 30 h after the surgical procedure. Muscle chemiluminescence showed a maximal increase of about twofold (control emission 10 +/- 1 cps/cm2) after 6-12 h of sepsis, while liver chemiluminescence increased by about 80% (control emission: 11 +/- 1 cps/cm2) after 24 h of sepsis. The activities of muscle antioxidant enzymes were found maximally diminished after 12 h of sepsis: 46% decrease for Mn-superoxide dismutase, 83% decrease for catalase, and 55% decrease for glutathione peroxidase. In liver, only catalase activity showed a 52% decrease after 24 h of sepsis. State 3 oxygen uptake of muscle mitochondria with either malate-glutamate or succinate as substrates was 40% decreased after 12 h of sepsis in both cases. State 4 oxygen uptake of muscle mitochondria was not affected. The rate of H2O2 production of muscle mitochondria after 12 h of sepsis with either malate-glutamate or succinate as substrates was increased about 2.5 times but was not affected when assayed in the presence of as rotenone and antimycin. The oxygen uptake of liver mitochondria isolated from septic rats did not show differences as compared with those of control rats after 6 to 24 h of sepsis. Oxidative stress appears to occur in skeletal muscle early at the onset of the septic syndrome, with inhibition of active mitochondrial respiration and inactivation of antioxidant enzymes.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8005530 TI - The increased susceptibility to hydrogen peroxide of the (post-)ischemic rat heart is associated with the magnitude of the low molecular weight iron pool. AB - Recently we have shown that intracellular low molecular weight (LMW) iron increases during ischemia. It is hypothesized that this increase in LMW iron during ischemia underlies the reported hydrogen peroxide toxicity toward ischemic hearts. To investigate this hypothesis, rat hearts were subjected to 15 min of no flow ischemia and reperfused with buffer saturated against 95% N2 and 5% CO2 (anoxic reperfusion) for 7 min. Hearts were then switched to buffer saturated against 95% O2 and 5% CO2 (reoxygenation) to assess functional recovery. The cardiac function recovered to 80 +/- 7% of the preischemic value. When the anoxic reperfusion was applied in the presence of 10 microM hydrogen peroxide, functional recovery after reoxygenation was 47 +/- 7%. Hearts that were perfused with deferoxamine before ischemia and then subjected to ischemia and anoxic reperfusion in the presence of 10 microM hydrogen peroxide recovered to 78 +/- 8%. Immediate reoxygenation after ischemia led to only 45 +/- 6% recovery of function. During ischemia, LMW iron increased from 49 +/- 45 to 183 +/- 45 pmol/mg protein (p < .05) and decreased to 58 +/- 38 pmol/mg protein (p < .05) during the subsequent anoxic perfusion. Rat hearts preloaded with deferoxamine showed a slightly higher LMW iron content than normal (85 +/- 23 and 49 +/- 45 pmol/mg protein, respectively; n.s.), which showed a small, nonsignificant increase up to 136 +/- 42 pmol/mg protein after 15 min of ischemia. No significant changes were found in reduced and oxidized glutathione content and glutathione peroxidase or catalase activities under those conditions.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8005531 TI - Effect of plasma on the degradation of hydroperoxides of unesterified linoleic acid and copper-peroxidized LDL. AB - The determination of lipid hydroperoxides in plasma and lipoproteins recently reached a clinical relevance in disorders such as atherosclerosis, where oxidative reactions have been suggested to play a fundamental pathogenetic role. The peroxide content of lipoproteins is usually measured after ultracentrifugation and extraction. During this procedure, some peroxides might decompose causing a too low recovery. To screen this possibility, the disappearance, in the presence of human plasma, of hydroperoxides of linoleic acid and Cu-oxidized low density lipoprotein (LDL) have been investigated, using both a iodometric titration and an enzymatic assay. While only in the presence of GSH plasma decomposes linoleic acid hydroperoxides quite rapidly, peroxides in Cu oxidized LDL were stable both in presence as well as in absence of GSH. This indicated that lipid hydroperoxides are stable in plasma and that peroxides of Cu oxidized LDL are not substrate for the glutathione-dependent peroxidase activity in plasma. The relevant decrease of the iodometric titre of LDL peroxides observed in the presence of elevated amounts of plasma was shown to be artifactual, since some compounds extracted from plasma do react with iodine generated by peroxides. Whole plasma itself, indeed, has been shown to reduce back to I- appreciable amount of free iodine. PMID- 8005532 TI - Hypothermia triggers iron-dependent lipoperoxidative damage in the isolated rat heart. AB - The extent and time course of recovery on return to normothermia were studied in isolated rat hearts, perfused with oxygen-saturated Tyrode's solution at 5-7 degrees C. After a 1-h hypothermia period, complete recovery was obtained on rewarming; after 3 h hypothermia irreversible deterioration of electrical and mechanical activities resulted. The level of lipid peroxidation, evaluated by the thiobarbituric acid (TBA) reaction, showed a dramatic transient increase on return to normothermia, accompanied by a decrease in the levels of reduced glutathione (GSH). Perfusion with iron chelator-containing saline completely prevented both the deterioration and the peak of lipid peroxidation. These results show that lipid peroxidation is responsible for the cold injury. It is proposed that lipid peroxidation is produced as the result of a cold-induced oxidative stress. PMID- 8005533 TI - Characteristics of an oxidant formed during iron (II) autoxidation. AB - When ethanol (100 mM) and the spin trapping agent DMPO were added to a solution of FeSO4 (0.1 mM) in phosphate buffer (40 mM), pH 7.4, the spectrum of the 1 hydroxyethyl radical spin adduct of DMPO could be detected by ESR spectroscopy. The ESR signal intensity of the 1-hydroxyethyl radical increased with higher concentrations of phosphate. Under these conditions, hydroxyl radical adducts could not be detected. However, if H2O2 (0.1 mM) was also added, the ESR spectra contained signals from both the hydroxyl and 1-hydroxyethyl radical adducts of DMPO. When ethanol was replaced with azide (100 mM) in these experiments, strong ESR signals from the azidyl radical adduct of DMPO were observed only in the Fenton system. The absence of hydroxyl radical adduct signals in the Fe(2+)-PO4 reaction could not be explained by instability of the hydroxyl radical adduct in the presence of Fe2+ or superoxide. Experiments with oxygen radical scavengers indicated that the oxidant formed during Fe2+ autoxidation was less reactive to benzoate, DMSO and tert-butanol than the hydroxyl radical. The available data indicate that the primary oxidant formed during Fe2+ autoxidation in phosphate buffer is not the hydroxyl radical, but may be an iron-oxygen complex such as a ferryl species. PMID- 8005534 TI - Oxidation of spin trap 5,5-dimethyl-1-pyrroline-1-oxide in an electron paramagnetic resonance study of the reaction of methemoglobin with hydrogen peroxide. AB - The possibility that methemoglobin (metHb) may function as a biological Fenton reagent to produce hydroxyl radical from hydrogen peroxide is investigated by electron paramagnetic resonance (EPR) spin-trapping techniques. The spin trap 5,5 dimethyl-1-pyrroline-N-oxide (DMPO) gives a nine-line EPR spectrum and no hydroxyl radical or superoxide spin adduct signals for the metHb/H2O2 system. From the known hyperfine splitting constants, the spectrum is assigned to 5,5 dimethylpyrrolidone-2(2)-oxyl-(1) (DMPOX), an oxidized derivative of DMPO. The likely involvement of the peroxidase activity of metHb in this reaction is suggested by the oxidation of DMPO to DMPOX by horseradish peroxidase as well. Furthermore, peroxidase inhibitors prevent the formation of DMPOX. Spectrophotometric assays confirm the peroxidase activity of metHb toward typical phenolic and nonphenolic substrates under the conditions used for the EPR experiments. The visible absorption spectra indicate the formation of a ferrylHb intermediate and its reduction by DMPO. Glutathione and ascorbic acid compete with DMPO as electron donors in the reaction to form thiyl and ascorbate radicals. Neither hydroxyl radical nor any other signal is observed when N-tert butyl-alpha-phenylnitrone (PBN) is used as the spin trap in the metHb/H2O2 system. It is concluded that methemoglobin-bound iron may not catalyze the Fenton reaction forming hydroxyl radical, but can oxidize a variety of substrates, including DMPO, in a peroxidase-type reaction. PMID- 8005535 TI - Internalization of human extracellular-superoxide dismutase by bovine aortic endothelial cells. AB - The high heparin-affinity subtype C of the secretory enzyme extracellular superoxide dismutase (EC-SOD) mainly exists on the outside of endothelial cell surface in the vasculature. Radioiodinated recombinant EC-SOD C(r-EC-SOD C) bound to cultured bovine aortic endothelial cells (BAE cells) at 4 degrees C with an association constant of 9.35 x 10(6) M-1 and maximum binding of 600 ng/dish (3109 ng/mg cellular protein). When incubated at 37 degrees C for 1 h, some 125I-r-EC SOD C was no longer releasable by heparin treatment, suggesting that 125I-r-EC SOD C was internalized by BAE cells. Since the internalization was inhibited in the presence of heparin in medium, this step was mediated by the binding to cell surface heparin sulfate proteoglycans. When cells containing internalized 125I-r EC-SOD C were incubated in newly added medium at 37 degrees C for up to 1 h, 54% of radioactivity was recovered in new medium. However, 71% of the radioactive materials released to the medium, presumably 125I-r-EC-SOD C and its metabolic products, had lost heparin binding activity. Much of internalized 125I-r-EC-SOD C was degraded to low molecular weight peptides, because 54% of the radioactive products released to the medium were trichloroacetic acid-soluble and 59% of them were below 10 kDa. About one-fourth of radioactive materials were recycled 125I-r EC-SOD judged from heparin-HPLC and Sephacryl S-200 column chromatography. In the presence of chloroquine, lysosomal protease inhibitor, the release of internalized 125I-r-EC-SOD C decreased to 59% compared with the control culture.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8005536 TI - Flow cytometric detection of hydrogen peroxide production induced by doxorubicin in cancer cells. AB - 2',7'-Dichlorofluorescin diacetate (DCFH-DA) has been previously used to study the oxidative burst of neutrophils induced by different stimuli. The method is based on the fact that DCFH-DA diffuses through the cell membrane and it is hydrolyzed by intracellular esterases to DCFH, which remains trapped within the cells. DCFH, a nonfluorescent compound, is able to react with free radical products, particularly with hydrogen peroxide, and to generate the fluorescent 2',7'-dichlorofluorescein (DCF). By flow cytometric detection of DCF fluorescence, an indirect measure of reactive oxygen species production in single cells may be obtained. Using a modified procedure to load cells of the human colon adenocarcinoma cell line LoVo with DCFH-DA, a significant fluorescence increase above the basal fluorescence level has been detected after treatment with doxorubicin doses as low as 0.4 microM. This increase is not detectable when the cells are preloaded with catalase, using a scraping method, and it is not due to doxorubicin own fluorescence. These experiments prove that the increase of DCF fluorescence intensity observed during doxorubicin treatment is not due to technical artifacts but it is attributable to free radicals produced in the cells by the drug. PMID- 8005537 TI - Antioxidant properties of Ambroxol. AB - We tested whether Ambroxol, a drug which stimulates the release of surfactant by pneumocytes type II, may also possess antioxidant properties. To assess the reactivity of Ambroxol with reactive oxygen species, we analysed its ability to decompose hydrogen peroxide (H2O2) and to inhibit the superoxide (O2.-)-dependent autooxidation of pyrogallol, hydroxyl radical (.OH)-mediated deoxyribose oxidation, and hypochlorous acid (HClO-induced chlorination of monochlorodimedon. Ambroxol was found to be a sufficient scavenger of HClO and .OH and also revealed the capacity to decompose H2O2. At concentrations of 25 and 70 microM, it inhibited HClO-induced chlorination of monochlorodimedon by 22 +/- 13 and 59 +/- 14%, respectively. Similarly, at concentrations of 1, 2, and 10 mM, Ambroxol decreased .OH-mediated deoxyribose oxidation by 47 +/- 11, 75 +/- 9, and 89 +/- 4%. In addition, at concentrations of 1 to 5 mM, it completely protected linoleic acid from .OH-induced peroxidative damage. Ambroxol had a weak effect on O2.(-) dependent autooxidation of pyrogallol. Our results indicate that Ambroxol has antioxidant activity, which may have clinical significance in protecting lung tissue from oxidant-induced injury. PMID- 8005539 TI - Effects of low-dose X-ray irradiation on biomembrane in brain cortex of aged rats. AB - We previously found that low-dose X-ray irradiation or radon (weak alpha-ray) inhalation increases SOD activities and reduces lipid peroxide levels in various organs of 7-week-old rats or rabbits. In this study, we examined how the changes of SOD activity, lipid peroxide level, and membrane fluidity of the cerebral cortex in aged male Wistar rats (65 and 91 weeks old) were affected by low-dose X ray irradiation (100 cGy or under) compared with those in 7-week-old rats, to elucidate the mechanism of aging inhibition. The following results were obtained: Although radiation sensitivity was observed to decreases with age, low-dose irradiation changed the Mn-SOD activity, lipid peroxide level, and membrane protein fluidity parameter of the cerebral cortex in the age rats to be closer to those in the youth. These findings suggest that the increased SOD activity induced by low-dose irradiation enhances biomembrane functions, and that the decrease of lipid peroxide level enhances the membrane protein fluidity. PMID- 8005538 TI - Ascorbyl free radical: a noninvasive marker of oxidative stress in human open heart surgery. AB - To assess the development of oxidative stress in cardiac ischemia/reperfusion, the resulting depletion of plasma ascorbate was monitored by electron spin resonance spectroscopic detection of ascorbyl free radical (AFR) in a homogeneous group of 12 patients undergoing aortic valve replacement. Dimethyl sulfoxide (DMSO) was used as an enhancer and stabilizer for AFR in plasma separated from blood samples collected 15 min before incision, 10 min before aortic declamping, and sequentially during the initial 30 min of reperfusion. Plasma DMSO/AFR levels of patients were found to be significantly lower than in healthy subjects (-25%), further decreased upon ischemia (-35%), dropped to their lowest values within the first 10 min of reperfusion (-46%), and did not recover their initial values within 30 min following reflow. Cardiac index measurements revealed a still depressed heart function 4 h postdeclamping and a more delayed tissue injury was evidenced by cardiac myosin and myoglobin release in plasma. DMSO/AFR levels at early reperfusion were slightly (+ 12%) higher in plasma obtained from coronary sinus samples than in plasma from peripheral blood, suggesting an extra ascorbate release from the injured heart tissue. The close analogy between these results and the reported measurements of other plasma markers of oxidative stress, including ascorbate, indicates that the present method could be of great value in clinical practice. PMID- 8005540 TI - Embryo cleavage rates after oocyte insemination with capacitated sperms in the presence or absence of follicular fluid. AB - The objective of the present study was to compare the rate of embryo cleavage after oocyte insemination with capacitated spermatozoa in the presence or absence of follicular fluid. In the first experiment, a total of 67 oocytes were inseminated with spermatozoa which had been submitted to part of the capacitation procedures in the presence of follicular fluid (21 oocytes) and with spermatozoa capacitated only with Menezo B2 culture medium (46 oocytes). Thirteen and 29 cleaved embryos were obtained, respectively (p = 0.89). In the second experiment, a total of 61 oocytes were inseminated with spermatozoa submitted to the entire capacitation procedure in follicular fluid (17 oocytes) and capacitated only with Menezo B2 culture medium (44 oocytes). Eleven and 31 cleaved embryos were obtained, respectively (p = 0.67). The absence of significant differences in cleavage rate between the two experiments indicates that the quality of the spermatozoa capacitation process is not changed by the addition of follicular fluid. PMID- 8005541 TI - Apoptosis in the cervix of pregnant rats in association with cervical softening. AB - Cervical ripening in gestation occurs spontaneously in a timely but species specific fashion as if it were genetically programmed. This study shows that the numbers of dying smooth muscle cells in the cervix increased along with cervical softening in pregnant rats from day 12 of gestation to day 21. The morphological characteristics of the chromatin cleavage in apoptosis are identified. Internucleosomal DNA fragments in the DNA preparations as well as the ladder pattern of double-stranded DNA observed on gel electrophoresis are observed. The deletion and decrease of the cell population in the cervices was demonstrated by a decrease of total DNA in these tissues. The interesting possibility is raised that programmed smooth muscle cell death in the cervix may be involved in the processes of the cervical ripening. PMID- 8005542 TI - Red cell deformability in gestational hypertension. AB - Erythrocyte deformability and red cell characteristics (MCV, MCHC, Hct) were studied in 18 patients with gestational hypertension, 24 normotensive primigravidae and 20 nonpregnant nulliparous women. The deformability of red cells was determined by red cell filtration in a filtrometer MF4 after prefiltration through cotton wool. We found a statistically reduced deformability in patients with gestational hypertension compared with normal pregnancy and nonpregnant controls. Our data suggest a strong correlation between red cell filterability and newborn weight (r = 0.59, p < 0.02). The deformability of erythrocyte in gestational hypertension mainly depends on the fluidity of the cell membrane (lipid content). Other factors are the hemoglobin viscosity and the cell membrane surface area/cell volume ratio. PMID- 8005543 TI - The outcome of pregnancy in antinuclear antibody-positive women. AB - The significance of antinuclear antibodies (ANA) was studied in 51 ANA-positive women who had had a total of 170 pregnancies. 60 ANA-negative age- and parity matched women with a total of 142 pregnancies served as controls. The perinatal mortality rate in the ANA-positive group was 18.6% (8/43), while there were no perinatal deaths in the ANA-negative control group. All the perinatal losses were stillbirths. The rate of spontaneous abortions was low in both groups, 2.0 vs. 3.3%, respectively. The ANA titer, complement-fixing activity and antigenic specificity did not correlate with the outcome of the pregnancy. Two infants of the ANA-positive women (3.9%) had a congenital atrioventricular heart block. In both cases the ANA was of the complement-fixing type. PMID- 8005544 TI - In vitro infection of human fetal membranes with Candida species. AB - To assess whether Candida species can penetrate intact fetal membranes under in vitro conditions, Candida albicans, Candida tropicalis, Candida guilliermondii, Candida pseudotropicalis and Candida glabrata were inoculated onto the surface of the maternal side of the membranes obtained from 4 pregnant women undergoing repeat cesarean section. After incubation under culture conditions, membranes were evaluated by histological examination. C. albicans inoculated onto the maternal side penetrated and passed to the fetal side and caused some degeneration of the structure of the membrane epithelium. The other four Candida species grew heavily on the maternal surface but did not penetrate and invade the membranes. This effect of C. albicans on fetal membranes may explain the potential mechanism in the development of Candida infections of the amniotic fluid, fetal membranes and possibly the fetus. PMID- 8005545 TI - Decreased ovarian blood flow may confound the tocolytic effect of ritodrine. AB - Pregnancies ending before 37 weeks gestation are the leading cause of infant morbidity and death. A recent study involving over 2,000 patients concluded that the beta-adrenergic agonist, ritodrine (Yutopar), the only tocolytic agent currently approved for clinical use, had no significant beneficial effect on perinatal mortality, the frequency of prolongation of pregnancy to term, or birth weight despite proven efficacy in suppressing uterine smooth muscle contraction for 24-48 h. Our previous studies in anesthetized, pregnant rats found that both isoproterenol and ritodrine decreased blood flow to the ovary, apparently via a 'vascular steal' phenomenon. Because decreased ovarian blood flow and blood flow mediated decrease in progesterone secretion represents one potential mechanism to explain the long-term ineffectiveness of beta-agonist tocolysis, ovarian blood flow studies were conducted in conscious, pregnant rats. Our results indicate that, indeed, ritodrine infusion significantly decreases ovarian blood flow (40%) in the conscious, near-term pregnant rat. PMID- 8005546 TI - Influence of maternal oxygen administration on the computer-analysed fetal heart rate patterns in small-for-gestational-age fetuses. AB - We observed the effect of maternal oxygen administration on the computerized fetal heart rate analysis in 34 small-for-gestational-age fetuses (SGA) antepartum in late pregnancy. A statistically significant increase in the number of accelerations and in variation was observed after maternal oxygen administration. PMID- 8005547 TI - Characterization of peripheral blood and peritoneal fluid mononuclear cell subsets in fertile and infertile women. AB - Mononuclear cell subpopulations from the peripheral blood (PB) and peritoneal fluid (PF) of fertile and infertile women were quantified by flow cytometry using a double-staining monoclonal antibody technique. No differences in the percentage distribution of mononuclear cells between fertile and infertile women were demonstrated when either the PB constituents or the PF components were compared to one another. When the mononuclear cell composition in the PB was compared with that in the PF however, the percentage of PF-activated T cells and monocytes was increased in both fertile and infertile women as opposed to that in the PB, while there was a decrease in T helper cells (fertile and infertile women) and natural killer cells (fertile women and infertile women with endometriosis). Even though shifts do exist in the immunocytes of PF from fertile and infertile women, evidence is lacking that the PF is an immunologic mediator of infertility. PMID- 8005548 TI - Exogenous estrogen therapy concurrent with clomiphene citrate--lack of effect on serum sex hormone levels and endometrial thickness. AB - The antiestrogenic action of clomiphene citrate (CC) is claimed to have an adverse effect on the development of the secretory endometrium. This effect can be assessed: (1) sonographically by measuring endometrial thickness, and (2) by serum hormone levels. The aim of this study was to evaluate whether administering ethinyl estradiol (EE) during CC treatment has any effect on endometrial thickness and/or hormone levels. Seventeen patients were treated with CC for one cycle and with CC plus EE in an adjacent cycle either before or after. The patients were followed by daily assessment of endometrial thickness, follicular growth and serum estradiol levels as well as midluteal prolactin and progesterone levels. We did not find any significant difference in either endometrial thickness, estradiol level, midluteal prolactin or progesterone levels between the two treatment protocols. We conclude that exogenous EE, in the dosage used in this study, does not overcome CC-induced alterations in endometrial thickness. PMID- 8005549 TI - Efficacy of placebo in the treatment of patients with amenorrhea. AB - Thirty-two amenorrheic patients were treated with a tablet oral placebo preparation for a period varying from 30 to 180 days. Another 24 amenorrheic patients were also treated with a placebo administered i.m. for a period varying from 30 to 120 days. As a consequence of the treatment, 27 patients (48%) had menstrual bleedings. The progestogen withdrawal test responsive patients were more responsive to placebo (73 vs. 14% in the progestogen withdrawal test nonresponsive, p < 0.001). The time lag between starting the medication and the first bleeding varied between 4 and 120 days with a mean value of 33.9 (SD 26.3). Oral placebo was more effective than the intramuscular form (56 vs. 38%, p < 0.05). PMID- 8005550 TI - Lymphokine-activated killer activity in women with endometriosis. AB - The aim of the present study was to investigate whether women with endometriosis displayed a decreased lymphokine-activated killer (LAK) activity. In 15 women with and 7 women without endometriosis the cytotoxicity against four different tumor cell lines--K562, the endometrium carcinomas AN3CA and RL95, the natural killer (NK)-resistant Daudi cell line--was investigated, using either freshly isolated peripheral blood mononuclear cells (PBMC) or recombinant interleukin (IL)-2-stimulated PBMC. In 5 additional women collagenase-DNase-digested endometrium was used, to investigate whether recombinant IL-2-activated lymphocytes displayed an increased cytotoxicity against fresh and cultured endometrial cells. The cytotoxicity of unstimulated PBMC toward K562, AN3CA and RL95 target cells was decreased in women with endometriosis compared to women without endometriosis (p < 0.05, for all). After recombinant IL-2 stimulation the cytotoxicity toward the four different target cells increased significantly, both in women with and without endometriosis. There was no difference in LAK-mediated cytotoxicity against the four tumoral cells between women with and without endometriosis. Significant LAK activity was demonstrated against both fresh and cultured (72 h) endometrial cells. The cytotoxicity of autologous lymphocytes against cultured endometrial cells was 31.0 +/- 17 versus 67.4 +/- 5.8%, using lymphocytes cultured in medium without and with recombinant IL-2, respectively (paired t test, p < 0.02).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8005551 TI - Infertility due to diseased pelvic peritoneum: laparoscopic treatment. AB - Thirty-one patients complaining of unexplained infertility for at least 36 months and diagnosed elsewhere were reassessed laparoscopically. After staining their pelvic peritoneum with concentrated methylene blue, they presented with extensive areas of dark blue discoloration, and were diagnosed as suffering from 'diseased pelvic peritoneum'. The levels of peritoneal CA 125 were assessed. At the end of the diagnostic procedure, bipolar electrocoagulation or defocalized laser beam therapy was performed to destroy the affected peritoneal areas, and to allow peritoneal regeneration. Twenty-five pregnancies were obtained following this treatment. A detailed description is given of the diagnosis and treatment procedures. PMID- 8005552 TI - A new approach to ovarian cystectomy: a combined laparoscopic and extra-abdominal microsurgical technique. AB - Our objective was to apply a new surgical technique to ovarian cystectomy combining the advantages of laparoscopy with the benefits of microsurgical principles, in an attempt to simplify the surgical laparoscopic procedure and reduce postoperative adhesion formation. Between May 1991 and March 1992, extracorporal ovarian cystectomy was performed in 27 patients who presented with persistent ovarian cysts at the department of gynecology of a large teaching hospital that receives primary referrals from public health care patients. Patients were referred with the diagnosis of a persistent ovarian cyst. Diagnosis was confirmed by pelvic bimanual examination, and transvaginal ultrasound. Cases where malignancy was suspected due to the presence of ascites, semi-solid or solid masses, demonstration of papillations within the ovarian cyst on ultrasound, or elevated CA-125 levels (unless endometriosis was suspected) were excluded from the study group. At laparoscopy, after inspection of the abdominal cavity the cyst was aspirated. The ovary was then extracted through a 2- to 3-cm lower-abdominal incision, cystectomy was meticulously performed according to microsurgical principles, and the repaired ovary was then returned into the abdominal cavity. Extracorporal cystectomy was successfully performed in 26 of 27 cases. The mean duration of the operative procedure was 55 min. The postoperative course was uneventful. Mean postoperative hospitalization time was 22.4 h. Over a follow-up period of up to 15 months, ovarian folliculogenesis was confirmed ultrasonographically. In the first 2 patients to undergo second-look laparoscopy, no adhesions were seen.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8005553 TI - Characterization of CA125 glycoprotein using 3 monoclonal antibodies with different specificities. AB - CA125 and CA130 in various tissues were characterized using the monoclonal antibodies OC125, 130-22, and 145-9. CA125 and CA130 were eluted in the same fraction in 130-22 affinity chromatography. A sandwich immunoradiometric assay using these antibodies in combination was established. When the solid phase of the assay was changed from OC125 to 145-9, the amount of 125I-OC125 that reacted with CA125 in the amnion increased more than that in other samples. On SDS-PAGE, CA125 and CA130 epitopes in the amnion migrated to different positions. These results indicate that CA125 and CA130 are located on different subunits of the same glycoprotein, and that their synthesis is regulated differently in various tissues. PMID- 8005554 TI - Interferon alpha 2b treatment of cervical intraepithelial neoplasia grade 2: modulation of natural killer cell. AB - The objective was to evaluate natural cytotoxicity of peripheral blood during interferon treatment in cervical intraepithelial neoplasia grade 2 (CIN2), as index of interferon activity. Twenty-one patients with CIN2, histologically proven, were treated with interferon alpha 2b (Intron A, Sheering-Plough Corp.), in a dose of 3,000,000 units three times per week for 8 weeks self-administered by intramuscular injection. The rate of remission to the interferon treatment was 38.1%. Eight healthy patients had a significant increase in natural killer activity during and after the treatment (p < 0.001), whereas the 13 nonresponder patients remained with low values of natural killer activity. By analyzing the basal natural killer activity before the treatment, the patients with clinicopathologic remission had a significantly higher mean value than nonresponder patients (p = 0.007). Notwithstanding the specimen exiguity, the individual basal natural killer activity seems to be a predictive parameter of interferon treatment response in patients with CIN2. PMID- 8005555 TI - 17 beta-Hydroxysteroid dehydrogenase: enzymatic activity and mRNA species in choriocarcinoma cells. AB - Two human choriocarcinoma cell lines, BeWo and Jar, were used as a model system to study 17 beta-hydroxysteroid dehydrogenase (17 beta-HSD) activity. Northern blot, Western blot and 3H-water assay were performed to investigate the mRNA species, protein and enzyme activity of 17 beta-HSD. Two sizes of 17 beta-HSD mRNA, 1.3 and 2.2 kb, were detected in BeWo and Jar cells. In BeWo cells the predominant mRNA species is 1.3 kb. Western blot analysis demonstrated high level of 17 beta-HSD immunoreactivity and the 3H-water assay demonstrated significant enzyme activity in BeWo cells. In contrast, in Jar cells, the predominant mRNA species is 2.2 kb. Jar cells contain very low 17 beta-HSD enzyme activity and Western blot failed to show detectable 17 beta-HSD immunoreactivity. It is possible that the 2.2-kb 17 beta-HSD mRNA cannot be efficiently translated into protein because of the presence of multiple AUGs and termination signals (UGAs, UAAs, and UAGs) at the 5'-untranslated and termination signals (UGAs, UAAs, and UAGs) at the 5'-untranslated region of the 2.2-kb mRNA. PMID- 8005556 TI - Epidural morphine bupivacaine combination for the control of autonomic hyperreflexia during labor. AB - The improvement in rehabilitation of young women with spinal cord lesions, combined with the fact that libido, fertility and child bearing remain intact, enables more such patients to conceive. The obstetric team is therefore bound to meet with such patients. Among the various complications of this condition during pregnancy is an acute life-threatening syndrome called autonomic hyperreflexia (AH), caused by an uncontrolled massive sympathetic discharge, which occurs in response to stimuli that reach the spinal cord below the lesion. Most authors agree that the best method of controlling AH during labor is by an epidural block which impends stimuli from reaching the spinal cord and thus provoking AH. Most authors could not completely abolish AH episodes using different medication epidurally. Herein we present a successful delivery using a combination of morphine bupivacaine epidurally. PMID- 8005557 TI - Environmental health education efforts for nurses. PMID- 8005558 TI - The impact of insulin upon atherosclerosis. PMID- 8005559 TI - Glucose transporter (GLUT 4) content and insulin receptor kinase activity in muscles of the LA/N-cp rat. AB - In this study we compared insulin binding activity, insulin receptor tyrosine kinase activity, and GLUT 4 protein content in six muscles from LA/N-cp rats and their lean controls. LA/N-cp rats had an approximate 20-fold increase in insulin concentration (837 +/- 113 vs 40 +/- 1), associated with significant (p < 0.01) decreases in both insulin binding activity per mg muscle and in muscle GLUT 4 content. Maximum insulin tyrosine kinase activity was also lower in muscle from LA/N-cp rats, but no difference was noted when tyrosine kinase activity was expressed per receptor. These data indicate that there are at least two defects in the insulin action cascade in muscle from LA/N-cp rats that contribute to the insulin resistance in these animals. PMID- 8005560 TI - Influence of protein nutrition on proteolytic activity and histone content in isolated mouse liver nuclei. AB - The proteolytic activity in isolated liver nuclei from mice subjected to different conditions of protein nutrition and its relationship with histones metabolism was studied. After five days of protein depletion, the nuclear azocaseinolytic activity increases concomitantly with a decrease in the concentration of histones. This activity resembles, in localization, optimum pH and inhibition behavior to rat liver chromatin neutral proteinase that degrades histones. Moreover, these proteins were identified as its main endogenous substrates. Refeeding of the protein depleted mice for 16h with a normal diet was unable to either diminish proteolytic activity or recover the normal histone level. Activity of the multicatalytic proteinase complex (proteasome) was not detected in nuclei. Furthermore, treatments known to activate this enzyme were ineffective. Taken together, these results suggest that nuclear proteases are mainly involved in the regulation of histone levels. PMID- 8005561 TI - Involvement of high-affinity binding site for EGF receptor in formation of rounding in A-431 epidermoid carcinoma cells. AB - The introduction of a bacterial aminoglycoside phosphotransferase gene (neo gene) into A-431 cells was found to result in disappearance of high-affinity binding sites of the epidermal growth factor receptor (EGFR), probably by affecting the phosphorylation level of the receptors. Using A-431 cells and their neo gene transfectants, we studied the relation between "rounding" and the high-affinity sites for EGF; and we also examined the role of protein kinase C (PKC) and A (PKA) in the EGF-induced cell rounding. Pretreatment of A-431 and their transfectant cells with 12-O-tetradecanoylphorbol 13-acetate (TPA; 100 ng/ml), an activator of PKC, for 30 min inhibited both the EGF-induced cell rounding and expression of high-affinity binding sites for EGF. However, both of these responses were recovered when cells were pretreated with TPA for 20 h, which treatment is known to result in depletion of PKC by a process called "down regulation". A similar recovery was also observed when cells were pretreated with forskolin (100 microM), an activator of PKA, for 30 min. Both cell rounding and EGFR high-affinity binding sites disappeared by activation of PKC, and reappeared by activation of PKA. These results suggest that the rounding of A-431 cells by EGF was induced via the high-affinity binding sites of EGFR. PMID- 8005562 TI - Cryopreservation of rat Leydig cells for in vitro and in vivo studies. AB - Leydig cells lose their ability to secrete testosterone following short-term in vitro culture. A procedure for effective storage of these cells would be useful. In this study, rat Leydig cells were cryopreserved in the presence of 10, 15 or 20% dimethylsulfoxide (DMSO) at approximately 1 degree C/min to -70 degrees C and then stored in LN2. After thawing, the cells cryopreserved in the presence of 15% DMSO showed the highest viability of over 75%. These cells secreted basal levels of testosterone in vitro as well as responded to hCG stimulation by secreting over 9-fold increase in testosterone. The viability of these cells was further confirmed by the demonstration of 3 beta-HSD positive cells under the kidney capsule of rats isografted with cryopreserved Leydig cells. This study demonstrated that purified rat Leydig cells can be cryopreserved and the cryopreserved cells retained normal function and were responsive to hCG stimulation. Cryopreservation is a simple procedure for long-term storage of functional Leydig cells. PMID- 8005563 TI - Pirenzepine decreases basal and stimulated GH secretion in patients with type 2 (non-insulin-dependent) diabetes mellitus. AB - Growth hormone (GH) hypersecretion has been described in diabetes mellitus and seems to be involved in the pathogenesis of diabetes complications. As pirenzepine (PZ), a cholinergic muscarinic antagonist, is able to inhibit GH hypersecretion in insulin-dependent diabetes mellitus (IDDM), we investigated whether PZ is also able to inhibit spontaneous and stimulated GH-release in non insulin-dependent diabetes mellitus (NIDDM). Ten non-obese well-controlled patients with NIDDM underwent in random order the following three double-blind one week treatments: placebo (PL), PZ at low dose (PL in the morning plus PZ 50 mg at 22 h) or high dose (PZ 50 mg at 8 h plus 100 mg at 22 h). Pirenzepine administration significantly (p < 0.05) decreased nocturnal GH release after both low and high dose (AUC, PL vs PZ: 107.3 +/- 26.5 vs 48.3 +/- 10.5 and 57.6 +/- 9.6 micrograms/L/h, respectively). The GH response to arginine infusion was significantly inhibited by PZ at high dose (AUC, 147.1 +/- 48.8 vs 444.7 +/- 194.3 micrograms/L/h, p < 0.01), but not at low dose. Glucose, insulin, glucagon and somatostatin responses to arginine infusion were not changed by pirenzepine treatment. In conclusion, the muscarinic blockade by PZ is able to inhibit the spontaneous and stimulated GH secretion also in NIDDM without affecting insulin secretion. PMID- 8005564 TI - Blunted growth hormone response to intravenous arginine in subjects with a spinal cord injury. AB - The influence of the activities of daily living on human growth hormone (hGH) release and plasma insulin-like growth factor (IGF-I) levels is not known. Individuals with spinal cord injury (SCI) and paralysis generally have reduced levels of activity compared with ambulatory subjects. We studied sixteen subjects with SCI and sixteen nonSCI subjects matched for age, gender and body mass index (BMI) as controls. After an intravenous infusion of arginine hydrochloride (30 g/subject over 30 minutes), mean plasma hGH values at 30 and 60 minutes were significantly lower in the group with SCI compared with the control group (3.4 +/ 0.7 versus 10.7 +/- 2.5 ng/ml, p < 0.01; and 5.2 +/- 1.5 versus 12.5 +/- 2.7 ng/ml, p < 0.05). Also, peak and sum hGH responses were significantly lower in the group with SCI than in the control group (5.8 +/- 1.5 versus 14.1 +/- 2.8 ng/ml, p < 0.01; and 15.2 +/- 3.1 versus 34.8 +/- 7.2 ng/ml, p < 0.02). Controlling for age and BMI, the results remained significant. However, the mean plasma IGF-I level was significantly lower in SCI subjects younger than 45 years old than in the similar subgroup of age-restricted controls (202 +/- 19 versus 324 +/- 27 ng/ml, p < 0.05), whereas, a comparison of subgroups of subjects 45 years or older did not reveal a significant difference. These findings support the hypothesis that decreased daily physical activity results in depression of the hGH/IGF-I axis in younger individuals with SCI and may be considered to be a state of premature aging.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8005566 TI - Masked insulin receptors in rat hypothalamus microsomes. PMID- 8005565 TI - Does exogenous hypermagnesaemia inhibit insulin secretion in patients with impaired glucose tolerance or non-insulin-dependent diabetes mellitus? AB - Acute exogenous hypermagnesaemia in healthy subjects retards glucose assimilation (Kg) and inhibits B cell function. The glycoregulatory effect of hypermagnesaemia was investigated in the course of the intravenous glucose tolerance test (IVGTT) in 16 subjects, incl. eight with impaired glucose tolerance (IGT) and eight with non-insulin dependent diabetes mellitus (NIDDM). Hypermagnesaemia was induced by intravenous infusion of 6 g MgSO4. The secretory response of insulin (IRI) and C peptide were expressed as the incremental area (IA of S-IRI and IA of S-C peptide). The results were compared with control IVGTT following infusion of saline. Hypermagnesaemia did not affect glucose assimilation in subjects with IGT as compared with control values nor in subjects with NIDDM. Hypermagnesaemia did not change IA of S-IRI nor of S-C-peptide in IGT as compared with control values (IA of S-IRI were 4308 +/- 1126 vs 3309 +/- 610 microU/ml x min and IA of S-C peptide 191 +/- 43 vs 177 +/- 46 ng/ml x min) (means +/- SEM). In NIDDM there was no significant difference between the response of C-peptide during hypermagnesaemia and the response during control IVGTT (IA were 72 +/- 20 ng/ml x min vs 73.5 +/- 22.4 ng/ml x min). As no significant insulin response to glucose was obtained after saline or magnesium in NIDDM, the effect of hypermagnesaemia was not possible to evaluate. In conclusion, no significant decline of glucose assimilation and B-cell function in IGT and NIDDM can be proved in the course of exogenous hypermagnesaemia.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8005567 TI - The protective effect of acetoaldehyde on the occurrence of alloxan-induced diabetes in rats. PMID- 8005568 TI - Prolactin (PRL) response to oral or vaginal bromoergocriptine in hyperprolactinemic women. PMID- 8005569 TI - Indications for orthotopic liver transplantation in fulminant liver failure. AB - The decision to undertake transplantation in a patient with fulminant liver failure requires consideration of many factors so that the physician may arrive at the most appropriate course of action. There are several definitions of fulminant liver failure used in current practice, all excluding patients with chronic liver disease. In the one most recently proposed, the terms hyperacute, acute and subacute liver failure are used to categorize groups of patients with different clinical appearances and progress. Patients in the hyperacute group have a better outcome with medical treatment than others, despite deeper levels of encephalopathy. The decision to proceed to transplantation should be undertaken in patients who fulfil criteria for a poor prognosis with medical management. For two groups, Hopital Paul Brousse, Paris, and King's College Hospital, London, criteria are based on analysis of large patient numbers, which can be applied at the bedside without recourse to complex analysis. Once a patient has been listed for transplantation, regular systems review must be undertaken because the development of irreversible multiple organ failure may preclude transplantation. Hepatectomy may occasionally have a role in stabilizing a patient awaiting a suitable organ. In less severe cases, auxiliary liver transplantation has been undertaken, and in some patients regeneration of the native liver has occurred, allowing withdrawal of immunosuppressive therapy. The results of orthotopic liver transplantation in fulminant liver failure have steadily improved over recent years, with reported 1-year survival rates of up to 80% in some series, yielding a good prognosis for certain groups of patients who previously had unacceptably high mortality. PMID- 8005570 TI - The need for a consensus agreement on indications of liver transplantation. PMID- 8005571 TI - Consensus Conference on Indications of Liver Transplantation. Paris, France, June 22-23, 1993. PMID- 8005572 TI - Indications for liver transplantation in primary biliary cirrhosis. PMID- 8005573 TI - The role of orthotopic liver transplantation in the management of sclerosing cholangitis. AB - Our recommendations are to manage asymptomatic patients with biannual clinical and biochemical follow-up examinations. Symptomatic non-cirrhotic patients who have diffuse SC should be enrolled in trials addressing the efficacy of medical therapy such as UDCA. Patients with diffuse disease and cirrhosis of the liver should be considered for liver transplantation. Symptomatic patients with a dominant stricture should first undergo rigorous investigation to rule out CCA. Disease in those noncirrhotic patients who are deemed to have benign strictures should initially be managed by means of dilation or surgical excision, although careful monitoring and review will be needed because most will continue with progressive disease, eventually showing signs of portal hypertension and cirrhosis. Patients with dominant strictures and cirrhosis should be considered for orthotopic liver transplantation. Liver transplantation in experienced units now offers more than 80% of patients a full and effective rehabilitation, with more than 75% alive at 5 yr. A progressive, advancing decompensating cholestatic disorder with an increasing risk of underlying malignancy can be stopped, giving the patient a high quality of life. More than half of patients report an improvement in the symptoms of their inflammatory bowel disease. PMID- 8005574 TI - Liver transplantation for hepatitis B virus-associated cirrhosis: a progress report. AB - Because of its importance as an indication for liver transplantation, the epidemiology of chronic hepatitis B disease is presented. Current knowledge relative to the pathobiological mechanisms of hepatitis B virus-related liver disease are presented, followed by a discussion of the treatment modalities currently available for use in hepatitis B virus-related liver disease. This is followed by an examination of their use in both potential transplant recipients and those who have been given liver transplants for hepatitis B virus disease. Finally, a summary of the current status of hepatitis B virus disease and liver transplantation is presented. PMID- 8005576 TI - Liver transplantation and alcohol: who should get transplants? AB - Medical selection criteria should be the same for all patients with end-stage liver disease and should aim for an acceptable outcome of the liver transplant procedure in matter of survival and quality of life, taking the scarce resources into account. The psychiatric selection criteria should aim at avoidance of recidivism of alcohol use in alcoholic patients. At least 6 mo of sobriety should be required. The patient must have a stable and supportive environment and should participate in an alcohol counseling program. A multicentered trial using uniform scoring criteria such as the Alcohol Prognosis Scale is needed to better define the selection of patients with alcoholic liver disease and long-term outcome of alcoholism after transplantation. PMID- 8005575 TI - Liver transplantation for hepatitis C virus-related cirrhosis. AB - Since the introduction of techniques to reliably identify antibody to the hepatitis C virus and quantitation of hepatitis C virus, there has been an increasing interest in the behavior of chronic hepatitis C infection with liver transplantation. Ninety-seven patients with chronic active hepatitis C and fifty nine patients with cryptogenic cirrhosis underwent 100 and 62 liver transplantation procedures, respectively, at a single institution. This represents 35% of the total liver transplantations performed during this time period. Twenty-three percent of transplants were performed in patients with evidence of chronic active hepatitis C. Patients and graft survival were excellent in both groups. One-, 2- and 3-yr patient survival rates for chronic active hepatitis C and cryptogenic cirrhosis were 94%, 89% and 87% and 84%, 84% and 73%, respectively. Hepatitis C can frequently be identified after transplantation. More than 95% of patients show persistence of antibody to the hepatitis C virus. Forty-one of 95 patients (surviving > 1 mo) showed recurrent hepatitis (initially seen 3 to 20 mo after transplantation), and 12 progressed to chronic active hepatitis. In 16 patients of the cryptogenic group in whom hepatitis developed, 11 were associated with de novo hepatitis C infection. Seven of these 11 cases went on to a chronic state. Of 11 deaths after transplant in the hepatitis C group, 2 were directly related to recurrent disease. There were 15 deaths in the cryptogenic group, 2 related to de novo hepatitis C. Patients were not serotyped. Interferon therapy was attempted in a small number of patients with disease, with inconclusive results.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8005577 TI - Contraindications to liver transplantation. PMID- 8005578 TI - Indications for liver transplantation in hepatobiliary malignancy. AB - Our personal experience with 172 patients, the results from the European Liver Transplant Registry and a review of the recent literature are summarized and discussed to define present indications for liver transplantation in hepatobiliary malignancy. The following conditions should be considered contraindications: advanced primary liver tumors with any extrahepatic spread, cholangiocellular carcinoma, hemangiosarcoma and liver metastases from nonendocrine primary tumor. Currently, "favorable" indications include uncommon tumors such as fibrolamellar carcinoma, epithelioid hemangioendothelioma, hepatoblastoma and metastases from endocrine tumors. Further indications may be nonresectable hepatocellular and proximal bile duct carcinoma in tumor stage II. Borderline indications are hepatocellular and proximal bile duct carcinoma in tumor stage III. In advanced tumors confined to the liver, transplantation should be restricted to multimodality treatment protocols. Although there are strong arguments for transplantation in early resectable hepatocellular carcinoma with underlying cirrhosis, it remains an open issue requiring further investigation in a controlled study using the same tumor classification. With regard to limited resources of donor organs, split-liver transplantation permits transplantation in tumor patients without neglecting those with benign diseases. PMID- 8005579 TI - Sequential treatment of biliary atresia with Kasai portoenterostomy and liver transplantation: a review. AB - Biliary atresia is the most frequent cause of chronic cholestasis in infants. When left untreated, this condition leads to death from liver insufficiency within the first 2 yr of life. The modern therapeutic approach consists of a sequential strategy with Kasai portoenterostomy as a first step and, in case of failure, liver transplantation. After portoenterostomy, no more than 20% to 30% of patients will live jaundice-free into adulthood. Illness in another third will be palliated, and these patients have extended survival, delaying liver transplantation to later childhood (2 to 15 yr). The remaining 30% to 40% will not benefit from the Kasai operation and will die of liver failure in infancy. The annual need of liver transplantation for biliary atresia is one case per million people. This indication represents 35% to 67% of the reported series of pediatric liver transplantation and between 5% and 10% of the indications for liver transplantation, all ages included. Approximately four of five children transplanted for biliary atresia will become long-term survivors with good physical and mental development; recurrence of the disease after transplantation has not been observed. Because most candidates are young children (< 3 yr) of small size (< 10 kg), there is a shortage of size-matched donors (which has been alleviated by the use of innovative techniques such as reduced and split livers). The resulting redistribution of the adult donor liver pool is ethically justified by the equal quality of the results after transplantation of a full-size or partial graft. PMID- 8005580 TI - Living donor for liver transplantation. AB - Since living related liver transplantation was first performed in 1989, more than 150 cases have been performed worldwide, mostly in the United States and Japan. This paper reports the first series of living related liver transplantation in Europe. Twenty living related liver transplantation surgeries were performed over a 13-mo period, with an overall patient survival of 85%. For patients who underwent elective transplantation (n = 13), the survival rate was 100%. Technical complications included one arterial thrombosis necessitating retransplantation and five bile leaks requiring surgical revision. The technical improvements that permit avoidance of these complications are discussed. A detailed description of the living related liver procurement is given. All procurements yielded grafts of excellent quality. No intraoperative complications occurred, and no reoperations were necessary. No heterologous blood transfusion was needed. In two patients, incisional hernias developed after wound infection. Living related liver transplantation does not absolve the transplant community of efforts to promote cadaveric organ procurement. Nevertheless, living related liver transplantation does have the advantage of a readily available graft of excellent quality, permitting transplantation with optimal timing under elective conditions. Several centers are now preparing living related segmental liver transplants, following the model of our protocol, for three reasons: (a) to obtain superior results compared with cadaveric liver transplantation; (b) to overcome cadaveric organ shortage and further reduce pretransplantation mortality and (c) to provide viable organs in countries where cadaveric organ procurement is not established. When performed by a team experienced in pediatric liver transplantation and in adult liver resection, living related liver transplantation is an excellent modality for the treatment of end-stage liver disease in children. PMID- 8005581 TI - Disease gravity and urgency of need as guidelines for liver allocation. AB - One thousand one hundred and twenty-eight candidates for liver transplantation were stratified into five urgency-of-need categories by the United Network for Organ Sharing (UNOS) criteria. Most patients of low-risk UNOS 1 status remained alive after 1 yr without transplantation; the mortality while waiting was 3% after a median of 229.5 days. In contrast, only 3% of those entered at the highest risk UNOS 5 category survived without transplantation; 28% died while waiting, the deaths occurring at a median of 5.5 days. The UNOS categories in between showed the expected gradations, in which at each higher level fewer patients remained as candidates throughout the 1-yr duration of study while progressively more died at earlier and earlier times while waiting for an organ. In a separate study of posttransplantation survival during the same time period, the best postoperative results were in the lowest-risk UNOS 1 and 2 patients (88% combined), and the worst results were those in UNOS 5 (71%). However, a relative risk cross-analysis showed that a negative benefit of transplantation may have been the result in terms of 1-yr survival for the low-risk elective patients, but that a gain in life extension was achieved in the potentially lethal UNOS categories 3, 4 and 5 (greatest for UNOS 3). These findings and conclusions are discussed in terms of total care of patients with liver disease, and in the context of organ allocation policies of the United States and Europe. PMID- 8005582 TI - Consensus statement on indications for liver transplantation: Paris, June 22-23, 1993. PMID- 8005583 TI - Two missense mutations causing tyrosinemia type 1 with presence and absence of immunoreactive fumarylacetoacetase. AB - Hereditary tyrosinemia type 1, due to a deficiency of fumarylacetoacetase (FAH), is characterized by progressive liver damage and renal tubular dysfunction and may occur in an acute or a chronic form. An Ala 134 to Asp (GCT to GAT) transition was found in one Turkish and two Norwegian patients with chronic tyrosinemia. SphI digestion of polymerase chain reaction (PCR) amplified genomic DNA identified the mutation and showed that the patients were heterozygous. All these patients had immunoreactive FAH protein in fibroblasts. Another Norwegian patient with chronic disease, without FAH immunoreactive material in fibroblasts, had a Pro 342 to Leu mutation (CCG to CTG). This mutation was identified by MspI digestion of PCR amplified genomic DNA, and the patient was heterozygous. Northern blotting showed FAH mRNA of normal size and amounts in all patients. Site directed mutagenesis and translation in a rabbit reticulocyte lysate demonstrated that both mutations abolished FAH activity. PMID- 8005584 TI - Multiplex PCR screening detects small p53 deletions and insertions in human ovarian cancer cell lines. AB - Mutations at the p53 tumor suppressor gene locus are a frequent genetic alteration associated with human ovarian carcinoma. Little information exists regarding whether mutational events occur other than point mutations and large deletions, causing loss of heterozygosity. Small intragenic deletions and insertions in the p53 gene have been observed in various human neoplasias. We developed a multiplex polymerase chain reaction (MPCR) screening assay to amplify the complete p53 coding region from genomic DNA in a single step. Deletions and/or insertions were found in six out of 11 newly established ovarian carcinoma cell lines. MPCR detected deletions as small as 2 bp, as confirmed by nucleotide sequence analysis. Most of the observed alterations (6/7) were homozygous or hemizygous. Structural aberrations of the p53 gene possibly leading to loss of p53 cell cycle control may be a consequence of a slipped-mispairing mechanism in rapid DNA replication during repetitious ovulation and wound repair of ovarian epithelial cells. MPCR may be a valuable tool for screening for possible p53 deletion and insertion mutations not only in ovarian cancer but also in other malignancies. PMID- 8005585 TI - A novel complex mutation in the LDL receptor gene probably caused by the simultaneous occurrence of deletion and insertion in the same region. AB - A novel complex mutation with the presence of both deletion and insertion in very close proximity in the same region was detected in exon 8 of the LDL receptor gene from two apparently unrelated Japanese families with familial hypercholesterolemia (FH). In this mutant LDL receptor gene, the nine bases from nucleotide (nt) 1115 to nt 1123 (AGGGTGGCT) were replaced by six different bases (CACTGA), and consequently the four amino acids from codon 351 to 354, Glu-Gly Gly-Tyr, were replaced by three amino acids, Ala-Leu-Asn, in the conserved amino acid region of the growth factor repeat B of the LDL receptor. The nature of the amino acid substitution and data on the families suggest that this mutation is very likely to affect the LDL receptor function and cause FH. The generation of this complex mutation can be explained by the simultaneous occurrence of deletion and insertion through the formation of a hairpin-loop structure mediated by inverted repeat sequences. This this mutation supports the hypothesis that inverted repeat sequences influence the stability of a given gene and promote human gene mutations. PMID- 8005586 TI - Unbiased transmission of mutant alleles at the human retinoblastoma locus. AB - The preferential transmission of the mutant allele to offspring from fathers who carry a germline mutation in the retinoblastoma gene was examined by analyzing 46 consecutive pedigrees. Among 75 offspring from 29 fathers, the ratio of carriers to noncarriers was 49%. Among the 106 offspring from 55 mothers the ratio was 57%. Neither ratio differs statistically from the expected 50%. When the analysis was limited to only those families with low-penetrance retinoblastoma, we still did not observe a biased transmission of alleles from fathers, although mothers did have an excess of carrier offspring of borderline statistical significance (the P-value was approximately 0.03). While we cannot rule out a biased transmission of alleles from some parents, there appears to be no such bias overall. PMID- 8005587 TI - Tight linkage of pyruvate kinase (PKLR) and glucocerebrosidase (GBA) genes. AB - Two polymorphisms, one in the liver-type pyruvate kinase gene (PKLR) and one in the glucocerebrosidase gene (GBA), both of which are on band q21 of chromosome 1, were found to be tightly linked. Each of three Gaucher disease mutations in 112 chromosomes studied was associated with a unique haplotype. With a conservative assumption about the length of time that the Gaucher disease mutation has been present in the Jewish population, we deduce that the genetic distance between these two loci is probably under 0.2 centimorgans. Four haplotypes are produced by these polymorphic loci, but two of these are relatively uncommon because the polymorphic sites are in linkage disequilibrium. Nonetheless these markers are potentially useful in the prenatal diagnosis of pyruvate kinase deficiency in families who have at least one affected child and may also be helpful in heterozygote detection in families with Gaucher disease where a specific mutation producing the disease in unknown. PMID- 8005589 TI - Identification of the mutations in the T-protein gene causing typical and atypical nonketotic hyperglycinemia. AB - We have investigated the molecular lesions of T-protein deficiency causing typical or atypical nonketotic hyperglycinemia (NKH) in two unrelated pedigrees. A patient with typical NKH was identified as being homozygous for a missense mutation in the T-protein gene, a G-to-A transition leading to a Gly-to-Asp substitution at amino acid 269 (G269D). Sibling patients of a second family with atypical NKH had two different missense mutations in the T-protein gene (compound heterozygote), a G-to-A transition leading to a Gly-to-Arg substitution at amino acid 47 (G47R) in one allele, and a G-to-A transition leading to an Arg-to-His substitution at amino acid 320 (R320H) in the other allele. Gly 269 is conserved in T-proteins of various species, even in E. coli, whereas Gly 47 and Arg 320 are replaced by Ala and Leu, respectively, in E. coli. The mutation occurring in more conservative amino acid residues thus results in more deleterious damage to the T protein, and gives the severe clinical phenotype, viz., typical NKH. PMID- 8005588 TI - Linkage analysis of the genetic determinants of high density lipoprotein concentrations and composition: evidence for involvement of the apolipoprotein A II and cholesteryl ester transfer protein loci. AB - We have tested for evidence of linkage between the genetic loci determining concentrations and composition of plasma high density lipoproteins (HDL) with the genes for the major apolipoproteins and enzymes participating in lipoprotein metabolism. These genes include those encoding various apolipoproteins (apo), including apoA-I, apoA-II, apoA-IV, apoB, apoC-I, apoC-II, apoC-III, apoE, and apo(a), cholesteryl ester transfer protein (CETP), HDL-binding protein, lipoprotein lipase, and the low density lipoprotein (LDL) receptor. Polymorphisms of these genes, and nearby highly polymorphic simple sequence repeat markers, were examined by quantitative sib-pair linkage analysis in 30 coronary artery disease families consisting of a total of 366 individuals. Evidence for linkage was observed between a marker locus D16S313 linked to the CETP locus and a locus determining plasma HDL-cholesterol concentration (P = 0.002), and the genetic locus for apoA-II and a locus determining the levels of the major apolipoproteins of HDL, apoA-I and apoA-II (P = 0.009 and 0.02, respectively). HDL level was also influenced by the variation at the apo(a) locus on chromosome 6 (P = 0.02). Thus, these data indicate the simultaneous involvement of at least two different genetic loci in the determination of the levels of HDL and its associated lipoproteins. PMID- 8005591 TI - PME of Unverricht-Lundborg type in the Mediterranean region: linkage and linkage disequilibrium confirm the assignment to the EPM1 locus. AB - Seven phenotypically homogeneous Mediterranean myoclonus families were studied using DNA markers from the genetically defined EPM1 region on chromosome 21. No recombinations between the disease phenotype and the markers studied were detected. Within the EPM1 region, the highest lod score value of 5.07 (at theta = 0.00) was reached at locus PFKL. Significant allelic association (P = 0.02) between the disease mutation and PFKL was detected suggesting a founder effect in Mediterranean myoclonus. However, haplotype data using four marker loci residing within 300 kb of each other and of EPM1 suggest the occurrence of more than one mutation. The data are compatible with Mediterranean myoclonus being caused by mutations in the EPM1 gene and strengthen the concept that a large subset of progressive myoclonus epilepsies conforms with Unverricht-Lundborg disease and that this subset is an etiologically homogeneous entity. PMID- 8005590 TI - Delineation of marker chromosomes by reverse chromosome painting using only a small number of DOP-PCR amplified microdissected chromosomes. AB - A new procedure for determining the chromosomal origin of marker chromosomes has been carried out. The origin of marker chromosomes that were unidentifiable by standard banding techniques could be verified by reverse chromosome painting. This technique includes microdissection, followed by in vitro DNA amplification and fluorescence in situ hybridization (FISH). A number of marker chromosomes prepared from unbanded and from GTG-banded lymphocyte chromosomes were collected with microneedles and transferred to a collection drop. The chromosomal material was amplified by a degenerate oligonucleotide-primed polymerase chain reaction (DOP-PCR). The resulting PCR products were labelled by nick-translation with biotin-11-dUTP and used as probes for FISH. They were hybridized onto normal metaphase spreads in order to determine the precise regional chromosomal origin of the markers. Following this approach, we tested 2-14 marker chromosomes in order to determine how many are necessary for reverse chromosome painting. As few as two marker chromosomes provided sufficient material to paint the appropriate chromosome of origin, regardless of whether the marker contained heterochromatic or mainly euchromatic material. With this method, it was possible to identify two marker chromosomes of a healthy proband [karyotype: 48,XY,+mar1,+mar2] and an aberrant Y chromosome of a mentally retarded boy [karyotype: 46,X, der(Y)]. PMID- 8005593 TI - Genetic mapping of 14 short tandem repeat polymorphisms on human chromosome 22. AB - We have constructed a linkage map of 14 short tandem repeat polymorphisms (11 with heterozygosity > 70%) on the long arm of human chromosome 22 using 23 non CEPH pedigrees. Twelve of the markers could be positioned uniquely with a likelihood of at least 1,000:1, and distributed at an average distance of 6.62 cM (range 1.5-16.1 cM). The sex-combined map covers a total of 79.6 cM, the female map 93.2 cM and the male map 64.6 cM. Based on comparisons between physical maps and other genetic maps, we estimate that our map covers 70%-80% of the chromosome. The map integrates markers from previous genetic maps and uniquely positions one marker (D22S307). Data from physical mapping on the location of four genetic markers correlates well with our linkage map, and provides information on an additional marker (D22S315). This map will facilitate high resolution mapping of additional polymorphic loci and disease genes on chromosome 22, and act as a reference for building and verifying physical maps. PMID- 8005594 TI - A unique origin for Sicilian (delta beta) (0)-thalassemia in 33 unrelated families and its rapid diagnostic characterization by PCR analysis. AB - Direct sequencing and restriction enzyme digestion of the polymerase chain reaction (PCR) product encompassing the breakpoint were used to characterize the Sicilian (delta beta)(0)-thalassemia deletion in 33 unrelated Italian subjects. All cases showed the same sequencing features at the breakpoint region, suggesting a unique origin for this deletion in Italy. We also describe a one step PCR assay for the rapid screening of homozygotes and carriers of Sicilian (delta beta) (0)-thalassemia by the simultaneous use of three specific oligonucleotides. This procedure could have an impact on genetic counseling of couples at risk for this type of thalassemia, and with respect to compound heterozygotes bearing a Sicilian chromosome. PMID- 8005592 TI - A base substitution at IVS-19 3'-end splice junction causes exon 20 skipping in pro alpha 2(I) collagen mRNA and produces mild osteogenesis imperfecta. AB - Molecular investigations on a young patient and her family were undertaken to identify the molecular defect responsible for a mild form of osteogenesis imperfecta (OI) with blue sclerae, dentinogenesis imperfecta and joint laxity. Analysis of collagenous proteins from the proband's fibroblasts showed the presence of two populations of alpha 2(I) chains, one normal and one migrating faster on SDS gels, thereby suggesting deletion of amino acid sequences. The faster migrating chains were retained mainly in the cell layer and not found in the extracellular matrix deposited by cultured fibroblasts. Chemical cleavage of mismatch (CCM) analysis on the patient's pro alpha 2(I) mRNA: normal cDNA heteroduplexes localized the molecular defect. cDNA sequencing revealed a deletion of exon 20 (54 bp) in about half of the molecules. Genomic DNA sequencing revealed heterozygosity for a G-to-C transversion of the last nucleotide of intron 19, which changed the 3' consensus splicing site. As a consequence pro alpha 2(I)mRNA was abnormally spliced from the last codon of exon 19 to the first codon of exon 21. To our knowledge, this is the first acceptor site mutation so far described in an OI patient. Restriction analysis indicated that the mutation was present also in three other affected family members. The full sequence of COL1A2 introns 19 and 20 are reported. PMID- 8005595 TI - Polymorphisms in the 3' untranslated region of the I kappa B/MAD-3 (NFKBI) gene located on chromosome 14. AB - The NF-kappa B transcription factor regulates the expression of a number of genes, including immune function and growth control loci, and several viruses. For example, the long terminal repeat of the human immunodeficiency virus contains NF-kappa B binding sites. NF-kappa B activity in the nucleus is regulated by a cellular inhibitory protein I kappa B. To analyze the potential role of these genes in genetic disease we have mapped the NF-kappa B (NFKB2) and I kappa B/MAD-3 (NFKBI) loci in a panel of somatic cell hybrids to chromosomes 4 and 14, respectively. Amplification of the 3' untranslated region of NFKBI allows the detection of three independent polymorphisms within 410 bp. In combination these polymorphisms were informative in 27 of 36 CEPH families and allowed the gene to be placed onto the linkage map of chromosome 14, between the D14S32 and D14S42 markers. PMID- 8005596 TI - Autosomal recessive polycystic kidney disease does not map to the second gene locus for autosomal dominant polycystic kidney disease on chromosome 4. AB - Linkage analysis in 19 families with autosomal recessive polycystic kidney disease (ARPKD) has shown that ARPKD is not linked to the recently assigned second gene locus for autosomal dominant polycystic kidney disease (ADPKD) on chromosome 4q (PKD2). Thus, there is strong evidence that ADPKD and ARPKD have different gene loci. PMID- 8005597 TI - Anticipation in hereditary dentatorubral-pallidoluysian atrophy. AB - Anticipation refers to the progressively earlier onset and increase in disease severity in successive generations. We studied four families with hereditary dentatorubral-pallidoluysian atrophy (DRPLA), a neurodegenerative disease, and anticipation was present in the mode of inheritance. In subsequent generations DRPLA shows an earlier onset and more severe as well as additional symptoms. Older onset patients suffer from cerebellar ataxia with or without dementia, whereas younger onset patients present as progressive myoclonus epilepsy syndrome, which consists of mental retardation, dementia, and cerebellar ataxia as well as epilepsy and myoclonus. Anticipation with paternal transmission was significantly greater than with maternal transmission. PMID- 8005598 TI - Assignment of the human 8.5 H gene to chromosome 5, region 5q35. AB - The human 8.5 H probe was isolated from a human cerebellum cDNA library with a probe corresponding to the coding region of the murine 8.5 M cDNA. This cDNA isolated from a murine cDNA library constructed from newborn cerebral hemispheres was selected because of its strong expression in embryonic neurons. Consequently the corresponding human gene could be a candidate for hereditary neurodegenerative diseases. The human 8.5 H gene was assigned by somatic hybrid analysis to chromosome 5; this chromosome contains the gene(s) for spinal muscular atrophy (SMA), a group of heritable degenerative diseases that selectively affect the anterior horn motor neuron of the spinal cord. The localization by in situ hybridization of 8.5 H on 5q35 excluded the possibility that this gene is identical to SMA. The SMA gene(s) was (were) known, from linkage analysis, to be in a region (5q11.2-q13.3) very distant from 5q35. PMID- 8005599 TI - Molecular and genetic characterisation of German families with paramyotonia congenita and demonstration of founder effect in the Ravensberg families. AB - Eighteen German families with a history of paramyotonia congenita (PC) were characterised by genetic and mutational analysis at the SCN4A locus, which encodes the alpha-subunit of the adult skeletal muscle sodium channel. We concentrated our analysis primarily on these families to test the hypothesis that a predominance of one common mutation occurs in all German PC families and that this mutation arose in a common ancestor originating in the North-West of the country. The present eighteen PC families exhibit two different mutations (R1448C and R1448H) on various SCN4A dinucleotide repeat haplotypes and therefore the majority of the mutations probably occurred independently. However, the R1448H mutation is extremely frequent in the North-West of Germany (Ravensberger Land) on a specific SCN4A microsatellite haplotype, indicating a founder effect within this subpopulation. Our results suggest that the R1448C/R1448H mutations are by far the most common to be associated with the PC phenotype in the German population. PMID- 8005600 TI - Molecular defects in erythropoietic protoporphyria with terminal liver failure. AB - We identified two additional mutations in the ferrochelatase gene in two Swiss patients with erythropoietic protoporphyria (EPP). Ferrochelatase cDNA from patients was amplified by the polymerase chain reaction (PCR) and subjected to mutation analysis by sequencing PCR products either directly or after subcloning. The first patient, who underwent liver transplantation because of terminal liver failure, was identified as having a single point mutation (C to T) at nucleotide 175 that resulted in a Gln to stop codon conversion in one allele of the gene. In the second case, in which the patient has so far no liver involvement, a two-base deletion (T899G900) was found in one allele. Frameshift as a result of the deletion creates a stop codon. This study presents two new genotypes of EPP, including one with liver failure, a rare and fatal form of EPP. PMID- 8005601 TI - Assignment of the gene encoding the human gonadotropin-releasing hormone receptor to 4q13.2-13.3 by fluorescence in situ hybridization. PMID- 8005602 TI - Assignment of the gene encoding the human thyrotropin-releasing hormone receptor to 8q23 by fluorescence in situ hybridization. AB - A cDNA for human thyrotropin-releasing hormone (TRH) receptor has been isolated from a human pituitary cDNA library. By using this cDNA as a biotinylated probe, the gene encoding the TRH receptor has been localized to chromosome 8q23 by in situ hybridization. PMID- 8005603 TI - (G)n-mononucleotide polymorphism in the human D4 dopamine receptor (DRD4) gene. PMID- 8005604 TI - TaqI dimorphic site in a human pancreatic phospholipase A2 (PLA2) gene localized on chromosome 12. AB - We report the identification of a TaqI dimorphic site in the first intron of a human phospholipase A2 gene that has been localized on chromosome 12. This single two-allele polymorphism was detected by DNA blot hybridization using a full length, 584 bp human phospholipase A2 cDNA isolated from a human lung lambda gt10 cDNA library. Fragment lengths were detected at either 1.3 kb or 2.2 kb. The PIC value of this dimorphism was 0.369 in a random population of 353 Caucasians. PMID- 8005605 TI - A NlaIII polymorphism within the human factor VII gene. AB - The polymorphism is located within exon 5 of the human coagulation factor VII gene and is silent at the amino acid level. The distribution pattern is similar in Caucasians and African Americans. This polymorphism may be useful for restriction fragment length polymorphism (RFLP) diagnosis of factor X deficiency as well as factor VII deficiency, since the factor X gene is closely linked to the factor VII locus. PMID- 8005606 TI - BglII identifies a frequent biallelic DNA polymorphism of the human RT6 gene. AB - A genomic probe of the human RT6 gene detects a frequent biallelic BglII polymorphism. Allele A has a frequency of 63%, whereas that of allele B is 37%. This restriction fragment length polymorphism provides the first known genetic marker for this gene. PMID- 8005607 TI - No maternal age relationship for polyploidy. PMID- 8005608 TI - Managing the cost of infection control. PMID- 8005609 TI - Trends in the perceived need for dental care: 1982-1991. PMID- 8005610 TI - Noise levels in the dental office. PMID- 8005611 TI - Why our patients don't trust us about infection control. PMID- 8005612 TI - Are you doing what you really want to do? PMID- 8005613 TI - Politically correct dentist. PMID- 8005614 TI - Regulation of expression of cell surface neolacto-glycolipids and cloning of embryonic chicken brain GalT-4 (UDP-Gal: GlcNAc-R beta 1-4 galactosyltransferase). AB - The biosynthesis of GM1 ganglioside (Gal beta 1-3GalNAc beta 1-4 (NeuAc alpha 2 3) Gal beta 1-4Glc-Cer) and nLcOse4Cer is catalyzed by two different beta galactosyltransferases GalT-3 (UDP-Gal: GM2 beta 1-3GalT) and GalT-4 (UDP-Gal: Lc3 beta 1-4GalT) respectively. Solubilized GalT-3 and GalT-4 have been purified 3,000-fold and 22,000-fold, respectively, from 11-19-day-old embryonic chicken brain. The purified GalT-3 transfers galactose to GM2 very actively (Km 33 microM), whereas acetyl GM2 is not an active substrate (Km 350 microM), GalT-3 and GalT-4 are classified as HYCARS (hydrophobic recognition site) and CARS (carbohydrate recognition sites), respectively. An anion-transport inhibitor DIDS (diisothiocyanato stilbene 4,4'-disulphonate), irreversibly inhibits both GalT-3 and GalT-4 activities by binding to a UDP binding site. Polyclonal antibodies against purified GalT-3 and GalT-4 inhibited these two purified activities and showed no cross reactivity on the western blots. RNA-PCR of 11-day-old embryonic chicken brain mRNA with PCR primers designed from the homologous coding regions of cloned sequences of beta 1-4 GalT of human, bovine, and murine-tissues produced a -600 bp cDNA fragment. Dideoxy-sequences of this fragment reveals it to be 74% similar to the nucleotide sequences of the cloned beta 1-4GalT from human liver. The cloned-600 bp cDNA was used to identify two mRNA transcripts (1.4 and 2.3 kb) from ECB by Northern blot analysis and four genomic DNA EcoRI fragments (18.6, 12.9, 10.5 and 3.7 kb) on a Southern blot analysis. PMID- 8005615 TI - Conserved structural features in glycoprotein processing glucosidase I from several tissues and species. AB - Glucosidase I initiates the processing of the oligosaccharide, Glc3Man9GlcNAc2, in newly assembled glycoproteins by excising the distal alpha 1,2-linked glucosyl residue in the oligosaccharide. Earlier, the enzyme purified from the ER of rat and bovine mammary gland has been found to have M(r) of 85 kDa, as examined by SDS-PAGE along with a domain structure in which a 39 kDa lumenally-oriented region is anchored to the ER through a transmembrane segment and a short cytoplasmic tail. These studies were further extended to include the enzyme from several different tissues of the rat, mouse, guinea pig and bovine mammary glands, sheep liver and pig kidney. Using anti-rat glucosidase I antibody as a probe and several biochemical parameters such as SDS-PAGE analysis, trypsin catalyzed digestion, ConA-binding, endo H susceptibility and peptide mapping analysis by cleavage of the tryptophanyl peptide linkages within the enzyme, it was found that glucosidase I in all of the tissue sources examined has an M(r) of 85 kDa and is cross-reactive to anti-rat glucosidase antibody. The enzyme is a high mannose glycoprotein, and has domain features in its structure; the enzyme from mouse, rat, guinea pig and bovine mammary glands and sheep liver is sequentially cleaved by trypsin to generate fragments of 69, 55 and 39 kDa. The rate of release of the different fragments differs for different sources, indicating some evolutionary changes in its primary structure. The trypsin released fragments from pig kidney enzyme are 69, 45 and 29 kDa in size, identical to the same observed earlier for pig liver.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8005616 TI - Molecular characterization of gangliotetraosylceramide (GA1) in normal human brain and its developmental change. AB - Several neutral glycosphingolipids have recently been purified from normal human brain to the criterion of migration as homogeneous bands in two different solvent systems. One of these has been permethylated and analyzed by gas chromatography. Stepwise specific exoglycosidase hydrolysis confirms its structure as GAl or Gal beta 1-->3GalNAc beta 1-->4Gal beta 1-->4Glc beta 1-->1Cer. The neutral glycosphingolipids of rat CNS have been examined in order to investigate changes in GA1 during critical ages of brain development. Employing the highly sensitive techniques of digoxigenin (DIG) immunostaining and Fluorescence Assisted Carbohydrate Electrophoresis (FACE), we have identified several previously uncharacterized long chain neutral glycosphingolipids in brain and myelin. A major band with Rf close to that of nLcOse5Cer purified from bovine erythrocytes has been identified as GA1 by immuno-TLC using mono-specific polyclonal anti-GA1 antisera. It appears in 5 day-postpartum (P5) developing brain, increases until 21 days (P21) and subsequently declines. This phasic change along with changes in other nonsialylated glycosphingolipids of the developing brain strongly suggests that GA1 and other neutral glycosphingolipids may play a mediator role(s) in brain development and/or myelinogenesis. PMID- 8005617 TI - Effects of monensin on glycosphingolipid metabolism in cultured human proximal tubular cells. AB - Effects of monensin, a monovalent cationic ionophore which disrupts Golgi apparatus and its related functions, on glycosphingolipid (GSL) metabolism were investigated in cultured human proximal tubular (PT) cells. Monensin (10(-6) M) stimulated [3H]Gal incorporation into GlcCer, GalCer and LacCer by 8.5-fold and 15-fold, respectively, in PT cells as compared to control. In contrast, [3H]Gal incorporation into GbOse3Cer and GM3 remained unchanged and that into GbOse4Cer was decreased 2-fold as compared to control. GSL measured by HPLC revealed that in cells incubated with monensin, GlcCer, GalCer and LacCer levels were increased 1.6-fold and 7-fold, respectively, whereas GbOse3Cer and GbOse4Cer levels were decreased several folds. Cells incubated with monensin contained 2.5- to 3-fold higher activity of alpha-galactosidase, beta-galactosidase and beta-glucosidase than control, whereas the activity of UDP-gal: glucosylceramide galactosyltransferase (beta-GalT-2) was 8-fold lower than control cells. Cells incubated with monensin took up and degraded one-half as much 125I-LDL as that of control cells. In control cells, exogenously derived [3H]LacCer on LDL was rapidly taken up and catabolized to monoglycosylceramide, or it was used for the endogenous synthesis of globotriosylceramide (trihexosylceramide), globotetraosylceramide (tetrahexosylceramide) and a ganglioside, GM3. In contrast, cells incubated with monensin accumulated most of the [3H]LacCer-LDL. Exogenously derived [3H]LacCer on LDL was catabolized to GlcCer, but was not utilized, for the synthesis of globotriosylceramide, globotetraosylceramide and GM3 in cells incubated with monensin.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8005618 TI - Sulphatide as a major glycosphingolipid in WHHL rabbit serum lipoproteins and its anticoagulant activity. AB - Sulphatide is found to be a major glycosphingolipid in serum lipoproteins of rabbit and its content is markedly elevated in serum of WHHL rabbit, an animal model for human familial hypercholesterolemia. On analysis of tissue sulphatide contents, serum appears to derive its sulphatide from liver (90%) and small intestine (10%) and passes on to aorta of WHHL rabbit which is found to have a large amount of sulphatide while none is found in normal aorta. Thus it seems that sulphatide finally accumulates in arterial walls along with the progression of atherosclerosis in WHHL rabbit. Since sulphatide at median concentration (8 nmole/ml serum) in various mammals is found to increase activated partial thromboplastin time by 25%, it is suggested that anticoagulant activity may be one of the physiological functions of sulphatide in serum. The observation of an increase in activated partial thromboplastin time by 2.5-fold on injection of sulphatide (10 mg/kg body wt) into rabbit suggests that sulphatide may be an effective and safe antithrombotic agent. PMID- 8005619 TI - Role of lipids in receptor mediated signal transduction. AB - A new strategy has been successfully applied to reconstitute the brain specific serotonin 5-HT1A receptor-G protein-adenylate cyclase complex. A mild method of tissue preparation gave a stable, membrane-bound form of the receptor (SBP) which retained its natural lipid content. Treatment of SBP with serotonin (1 microM) and 3-[(3-cholamidopropyl) dimethyl ammonio]-1-propanesulphonate (CHAPS) (2%) solubilized the ligand-receptor-G protein-ligand complex along with the associated phospholipids and cholesterol. Dialysis of this extract (SBDS) against buffer containing 25% ethylene glycol produced a stable, reconstituted and active preparation (SBDSE) of vesicles which upon centrifugal separation followed by gentle resuspension retained 95-100% [3H] 8-OH-DPAT binding activity as well as 60% [3H] GppNHp binding and adenylate cyclase activities of SBDSE. The reconstituted receptor preparation compared well with the membrane-bound form in displaying a similar value for KD (2.1 nM) and a single affinity state for [3H] 8 OH-DPAT binding (Bmax = 118 fmol/mg). However, in sharp contrast to the membrane bound receptor which was negatively coupled to adenylate cyclase, agonist treatment of the solubilized and reconstituted receptor resulted in an increase in adenylate cyclase. This change in receptor-adenylate cyclase coupling following reshuffling of membrane lipids during solubilization and reconstitution suggested that membrane lipids could have a profound effect on receptor-effector coupling. To study the effect of membrane lipid composition on receptor-mediated signal transduction in a stabler and more natural system, neural cells derived from different parts of the brain (hippocampus, HN2; CNS, NCB-20; dorsal root ganglion, F-11) and a non-neural cell line (CHO), all with differing membrane lipid compositions, were selected. Since no known cell line contains the serotonin 5-HT1A receptor (5-HT1A-R), stable transfection of the selected cell lines with a DNA construct encoding the human 5-HT1A-R was carried out and this resulted in a late increase of [3H] 8-OH-DPAT binding in the stationary phase only in the cell lines of neural origin. In the non-neural cell line (CHO), which also displayed marked difference in membrane lipids, the receptor was positively coupled to the phospholipase C-IP3-[Ca2+]i cascade. Even though GPLC was present in the NCB-20 and F-11 cells as evidenced by a bradykinin receptor-mediated increase in inositol phosphates in these cells 8-OH-DPAT treatment resulted in no change in phospholipase C in any of the cell lines of neural origin.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8005620 TI - Influence of primary and secondary structures of oligosaccharide chain on the aggregative and geometrical properties of gangliosides. AB - The aggregative and geometrical properties of gangliosides have been compared and discussed. It is shown that, due to the steric packing features of gangliosides, significative considerations can be made on the primary and secondary structures of their head group, starting from their cooperative behaviour, supporting NMR direct observations. PMID- 8005621 TI - Developmentally-regulated cell surface N-linked oligosaccharides participate in intercellular cohesion in Dictyostelium discoideum. AB - The ability of purified plasma membrane glycoconjugates to inhibit the EDTA resistant agglutination between aggregation-stage cells of Dictyostelium discoideum has suggested that receptor binding of these glycoconjugates provides a basis for cell-cell cohesion during aggregation. This has been tested by analysis of a series of mutants with different defects in the assembly of N linked oligosaccharides. Mutant HL241 lacks outer branch components of N-linked oligosaccharides and fails to aggregate or express EDTA-resistant cohesion. HL244 makes unsulphated but otherwise normal N-linked oligosaccharides, generates multiple tips on aggregated cell mounds in some clones, and shows abnormally strong EDTA-resistant cohesion. Two mutants that are temperature-sensitive for complete processing of N-linked oligosaccharides are also temperature-sensitive for expression of both aggregation ability and EDTA-resistant cohesion. A revertant that recovered essentially normal N-linked oligosaccharide processing at the restrictive temperature has also recovered its ability to aggregate and to agglutinate in EDTA. PMID- 8005623 TI - Kinetics of fusion with cells of reconstituted Sendai virus envelopes lacking hemagglutinin-neuraminidase. AB - The fusion potential of reconstituted Sendai virus envelopes containing only the F protein (F-virosomes) has been assessed. F-virosomes and F,HN-virosomes were prepared by solubilization of the intact virus in Triton X-100 followed by its removal using SM-2 biobeads. Viral envelopes containing HN whose disulphide bonds were irreversibly reduced (HNred) were also prepared by treating the envelopes with dithiothreitol followed by dialysis. Both F-virosomes and F,HNred-virosomes hemolysed red blood cells in the presence of wheat germ agglutinin. The rates and extent of hemolysis induced by these virosomes were, however, significantly lower than that induced by F,HN-virosomes. Using a fluorescence probe based membrane mixing fusion assay, F- and F,HNred-virosomes were found to fuse with cultured HeLa cells in the presence of wheat-germ agglutinin. A direct comparison of the fusion activity of F,HN-virosomes and F-virosomes was made by using desialylated HepG2 cells as target containing the asialoglycoprotein receptor (ASGP-R) that binds to a terminal beta-galactose moiety of F protein. A 2- to 3-fold enhancement in the fusion rate when HN was included in the viral envelope was observed. Based on the kinetic data, a model for fusion of paramyxo-virosomes with HepG2 cells is proposed. PMID- 8005622 TI - Peptide mapping reveals differences in the non-glycosylated domains of cystic fibrosis and normal tracheobronchial mucins. AB - Tracheobronchial mucins from lung mucus secretions of healthy individuals and from patients with cystic fibrosis (CF) were purified according to a protocol established in our laboratory. Following digestion of the purified, reduced alkylated mucin (free of 118 kDa and 70 kDa components) with trypsin-L-1 tosylamido-2-phenylethyl chloromethyl ketone, three fractions (TR-1, TR-2 and TR 3) were observed upon chromatography on a Superose 6 column using FPLC. TR-1 (glycosylated fraction) contained all of the carbohydrate, while TR-2 and TR-3 fractions had no detectable sugars. Comparison of the amino acid composition of TR-1 fractions from normal and CF individuals revealed no significant differences, while the TR-2 fractions from these mucins showed noticeable differences. Peptide mapping of TR-2 fractions from normal and CF mucins was performed on a C18 reverse phase column using FPLC. The peptide maps of normal mucins were markedly different from CF mucins. A greater number of peptides were seen in the TR-2 fractions of normal mucins when compared to CF mucin TR-2 fractions. In addition, normal TR-2 fractions appeared to be comprised of more hydrophobic peptides when compared to CF TR-2 fractions. These data provide evidence of possible structural differences in the non-glycosylated regions of CF and non-CF mucins, since the TR-2 fractions are essentially derived from the T domains in the "naked" stretches of the mucin polypeptide backbone. PMID- 8005624 TI - Further characterization of glucose-specific peanut root lectin (PRA II). AB - Amino acid analysis of PRA II, a glucose-specific lectin isolated from 7 day-old peanut seedling roots shows that this lectin is rich in glycyl (103 per mole) and seryl residues (59 per mole), and poor in essential amino acids, the acidic amino acid content is higher than the basic amino acids and that its amino acid composition differs from its seed counterpart (PNA), although neither of the lectins contains cystein. PRA II has two carbohydrate binding sites per molecule as determined by equilibrium dialysis. Modifications of the specific amino acid residues of the lectin with group specific reagents indicate that hydroxyl group of tyrosine is involved in the binding of carbohydrate to PRA II. PMID- 8005625 TI - Potentiation of ricin cytotoxicity by liposomal monensin under in vitro and in vivo conditions. AB - Effect of monensin, intercalated in liposomes on the cytotoxicities of ricin, Pseudomonas exotoxin A and diphtheria toxin in phagocytic and non-phagocytic cells as well as in mice has been studied. Intercalation does not disturb the integrity of the liposomal bilayer and substantially enhances the cytotoxicities of ricin and Pseudomonas exotoxin A in both phagocytic and non-phagocytic cells while it has no effect on diphtheria toxin. The observed effect is highly dependent on the liposomal lipid composition as well as cell types. The potentiating ability of monensin in neutral vesicle is 2.2-fold higher than in negatively charged vesicles in non-phagocytic cells while no difference was observed in phagocytic cells. Incorporation of stearylamine in liposomes reduces the potentiating effect of monensin. Liposomal monensin has also been found to enhance the cytotoxicity of ricin in mouse in vivo in a dose-dependent manner and is maximal when ricin is injected within 60 min of monensin injection. Liposomal monensin remains in circulation for 2 hr while free monensin remains only for 15 min. Tissue distribution studies reveal that liposomal monensin is present mainly in the liver and spleen which are also the major sites for ricin accumulation. Thus liposome is found to be an effective delivery vehicle for monensin to potentiate the cytotoxicity of immunotoxins or hormonotoxins and could prove useful for selective elimination of cancer cells. PMID- 8005626 TI - Use of specific polyclonal antibodies for site specific drug targeting to malaria infected erythrocytes in vivo. AB - The possibility of using specific polyclonal antibodies for effective site specific drug targeting to malaria infected erythrocytes has been examined. For this purpose, rabbit polyclonal antiserum was raised against Plasmodium berghei infected mouse erythrocytes (IRBC) and extensively absorbed with normal erythrocytes (NRBC). Absorbed antiserum specifically recognized IRBC. F(ab')2 fragments of these antibodies were coupled to chloroquine (chq) laden liposomes. These immunoliposomes when tested in vivo significantly suppressed malarial infection in mice. PMID- 8005627 TI - Surface carbohydrates in cell-sociology. PMID- 8005628 TI - Pathology of subacute hepatic failure. PMID- 8005629 TI - Further experience of late onset hepatic failure. PMID- 8005630 TI - Fulminant and subfulminant hepatitis in Japan--etiological considerations. PMID- 8005631 TI - Subacute hepatic failure: unresolved issues. PMID- 8005632 TI - Liver transplantation for subfulminant hepatitis. AB - The preceding discussion has characterized the various types of viral hepatitis, both common and unusual, that can lead to subfulminant hepatic failure. Whenever specific medical therapy exists, it is preferred. If the disease has progressed sufficiently to prohibit survival inspite of medical therapy, OLT is indicated under the umbrella of continuing specific medical therapy. Conversely, if no medical therapy exists, OLT is the only possible therapy but should be used only if extrahepatic disease processes do not prohibit survival. Hopefully, with better and more effective means of immunosuppression, immunosuppression monitoring and the development of additional medical therapies for viruses, OLT will be used less often in cases of subfulminant viral hepatitis in the future. PMID- 8005633 TI - Therapeutic guidelines for subacute hepatic failure. PMID- 8005634 TI - Subacute hepatic failure: definition, nomenclature and criteria for diagnosis. PMID- 8005635 TI - Subacute hepatic failure--experience at the Institute of Medical Sciences, Srinagar. PMID- 8005636 TI - A "new" blood-group character related to the ABO system. 1952. PMID- 8005637 TI - Transfusion associated HIV infection in patients with haematologic disorders in southern India. AB - Seventy patients with congenital coagulation disorders (group A) and 202 other patients (group B) attending the Haematology clinic at the Christian Medical College and Hospital, Vellore (India) were screened for HIV infection between March 1989 and April 1991. Fifty five patients in group A and 131 patients in group B had received blood or blood products in the past. Nineteen transfused patients (9 in group A and 10 in group B) had received blood or blood products exclusively from the hospital blood bank and none of them was HIV infected. Among the remaining 167 transfused patients, 14 (30.4%) of the 46 patients in group A and 6 (4.9%) of the 121 patients in group B were found to be positive for HIV. In group A, 13 of the 14 infected patients had received commercially available cryoprecipitate which was thus found to be the most frequent source of infection. In group B the source of infection was most probably unscreened HIV infected blood which was transfused. PMID- 8005638 TI - Comparison of polyacrylamide gel electrophoresis & silver staining method with ELISA for rotavirus detection. AB - A total of 421 human fecal samples were examined for the presence of rotavirus by enzyme-linked immunosorbent assay (ELISA) and by a modified polyacrylamide gel electrophoretic (PAGE) analysis of viral genome. Similar results by both methods were seen in 412 (97.86%) samples. The proportion of ELISA + PAGE - samples (2/421) was lower than the proportion of ELISA - PAGE + samples (7/421). This difference was not significant. The modified PAGE technique for the detection of viral RNA was found to be a rapid, simple, reliable and less expensive technique. PMID- 8005639 TI - Detection of albumin & immunoglobulin on surface of Brugia malayi mf by immunofluorescence. PMID- 8005640 TI - Strip ELISA for the detection of IgG antibodies to Toxoplasma gondii. AB - An enzyme linked immunosorbent assay (ELISA) has been developed using a polycarbonate coated strip and penicillinase for the detection of IgG antibodies to T. gondii. Of 40 serum samples from patients clinically suspected to have toxoplasma infection, 24 were positive for IgG antibodies to T. gondii. Strip ELISA showed 95.83 per cent sensitivity and 89.4 per cent specificity. This method is simple (end result assessed visually), sensitive (detection of antitoxoplasma IgG antibodies to a level of 15 IU/ml) and reproducible (5.9 and 11.6 intra and inter percentage of coefficient of variation respectively). PMID- 8005641 TI - Antifungal activity of allylamine derivatives. AB - The antifungal activity of the two allylamine derivatives, naftifine and terbinafine was investigated against 25 clinical isolates of filamentous fungi by agar dilution method. The isolates included Aspergillus sp. (10), Penicillium sp. (3), Cladosporium sp. (3), Rhizopus sp. (3), Paecilomyces sp. (2), Syncephalastrum sp. (1), Pyrenochaeta romeroi (1), Piedraia hortae (1) and Mortierella sp. (1). Terbinafine was found to be more active than naftifine, inhibiting 50 per cent (MIC 50) and 90 per cent (MIC 90) of the isolates of Aspergillus sp., at 0.1 and 0.5 microgram/ml respectively. The MIC 50s for the other isolates of hyalohyphomycetes, dematiaceous fungi and zygomycetes were 1, 5 and 100 micrograms/ml respectively. Naftifine inhibited 50 and 90 per cent of the Aspergillus sp., at 1 and 5 micrograms/ml, respectively. The MIC 50s for the other hyalohyphomycetes, dematiaceous fungi and zygomycetes were 5, 10 and 100 micrograms/ml respectively. PMID- 8005642 TI - Effect of cigarette smoking on thyroid hormone homeostasis. AB - Serum thyroxine (T4), triiodothyronine (T3), thyroid stimulating hormone (TSH) and thiocyanate (SCN) levels in 40 smokers smoking filter or non-filter cigarettes were compared to those in 20 control subjects. Both types of cigarette smoking resulted in a decrease in T4 (P < 0.01) and increase in TSH (P < 0.05) to the same degree as compared to control. T3 was found to be higher in the smokers but the rise was not significant. SCN was elevated significantly in the smokers. The filter attached to the cigarette was found to have little or no effect on the alteration of the levels of the biochemical indices studied. PMID- 8005644 TI - Effect of leucopelargonin derivative from Ficus bengalensis Linn. on diabetic dogs. AB - Dimethoxy ether of Leucopelargonidin-3-0-alpha-L rhamnoside isolated from the bark of the Indian Banyan tree Ficus bengalensis Linn. was tested for antidiabetic effect. At a medium effective dose (100 mg/kg) on oral administration, the compound showed significant hypoglycemic and serum insulin raising action in normal as also moderately diabetic dogs (induced by alloxan) during a period of two hours. The mechanism of action of the glycoside compound seems to be similar to that of drugs which stimulate insulin secretion. On acute and chronic administration in single doses of 0.2-1.8 g/kg to different groups of mice and daily administration of 100, 250 and 500 mg/kg to rats for a period of one month respectively did not show any toxic effect and the compound was not lethal even at the high dose of 1.8 g/kg in experimental animals. PMID- 8005643 TI - Isolation & chemical composition of lung surfactant from human amniotic fluid. AB - Lung surfactant was isolated from human amniotic fluid collected at term and studied with reference to the material isolated from human and rabbit lung lavage. The isolated material showed 58 per cent lipid by dry weight, 29 per cent protein and relatively smaller amounts of nucleic acids, sialic acid and hexose. Phosphatidyl choline was the predominant phospholipid species and accounted for 46 per cent of the total lipid by weight, followed by phosphatidyl glycerol (7%) and phosphatidyl ethanolamine (5%). Cholesterol was the major neutral lipid fraction present (10%) and was almost entirely in the free form. Other lipid fractions present in minor quantity were triglycerides, esterified cholesterol, phosphatidyl serine, phosphatidyl inositol and sphingomyelin. The material contained a very high degree of alkaline phosphatase activity, while other enzymes such as acid phosphatase, glucose-6-phosphatase, ATPases, 5'-nucleotidase and beta-N-acetyl glucosaminidase were also present. PMID- 8005645 TI - Some behavioural effects of chloroquine in rats suggesting dopaminergic activation. AB - The effect of chloroquine on open-field behaviour, apomorphine induced stereotypies and haloperidol and pimozide-induced catalepsy was studied in rats. Chloroquine (2.5-10 mg/kg, ip) significantly increased the locomotion frequently of rats in the open-field and also markedly enhanced apomorphine (0.4 mg/kg, sc) induced locomotion. Haloperidol (0.25 mg/kg, ip) antagonised the increased locomotion frequency produced by chloroquine (5 mg/kg, ip), apomorphine (0.4 mg/kg, sc) and chloroquine plus apomorphine. L-Dopa (50 mg/kg, sc) and benserazide (12.5 mg/kg, ip) plus L-Dopa (50 mg/kg,sc) significantly increased chloroquine (5 mg/kg, ip)-induced locomotion. SCH 23390 (0.2 mg/kg, sc) and sulpiride (30 mg/kg, ip), on the other hand, attenuated chloroquine (5 mg/kg, ip) induced locomotion. Chloroquine (2.5-5 mg/kg, ip) elicited stereotyped behaviour in rats and significantly potentiated apomorphine (2 mg/kg, sc)-induced stereotypies. Haloperidol (0.25 mg/kg, ip) markedly reduced the stereotypies produced by both chloroquine (5 mg/kg, ip) and apomorphine (2 mg/kg, sc). Both chloroquine (2.5-10 mg/kg, ip) and apomorphine (0.4 mg/kg, sc) significantly delayed the onset and decreased the intensity of catalepsy induced by haloperidol (0.25mg/kg, ip) and pimozide (2mg/kg, ip) respectively. These findings indicate that chloroquine, in low doses, produces excitatory effects and that dopaminergic mechanisms may be involved in the observed effects of chloroquine. PMID- 8005646 TI - The cataract problem. PMID- 8005647 TI - The biology of cataract. The Hyderabad Cataract Research Group. PMID- 8005648 TI - Acid phosphatase and lipid peroxidation in human cataractous lens epithelium. AB - The anterior lens epithelial cells undergo a variety of degenerative and proliferative changes during cataract formation. Acid phosphatase is primarily responsible for tissue regeneration and tissue repair. The lipid hydroperoxides that are obtained by lipid peroxidation of polysaturated or unsaturated fatty acids bring about deterioration of biological membranes at cellular and tissue levels. Acid phosphatase and lipid peroxidation activities were studied on the lens epithelial cells of nuclear cataract, posterior subcapsular cataract, mature cataract, and mixed cataract. Of these, mature cataractous lens epithelium showed maximum activity for acid phosphatase (516.83 moles of p-nitrophenol released/g lens epithelium) and maximum levels of lipid peroxidation (86.29 O.D./min/g lens epithelium). In contrast, mixed cataractous lens epithelium showed minimum activity of acid phosphatase (222.61 moles of p-nitrophenol released/g lens epithelium) and minimum levels of lipid peroxidation (54.23 O.D./min/g lens epithelium). From our study, we correlated the maximum activity of acid phosphatase in mature cataractous lens epithelium with the increased areas of superimposed cells associated with the formation of mature cataract. Likewise, the maximum levels of lipid peroxidation in mature cataractous lens epithelium was correlated with increased permeability of the plasma membrane. Conversely, the minimum levels of lipid peroxidation in mixed cataractous lens epithelium makes us presume that factors other than lipid peroxidation may also account for the formation of mixed type of cataract. PMID- 8005649 TI - Microphthalmos with cyst: a clinical study. AB - Defects in closure of embryonic fissure and invagination of optic vesicle results in varied clinical presentation of microphthalmos with cyst. In our study, three patients had microphthalmos with cyst in one of their orbits. The cyst presented either as a swelling in the lower lid or as a sinus with purulent discharge associated with absent or small sized eyeball. The microphthalmic eye showed a spectrum of posterior segment abnormalities such as retinal disorganisation, gliosis, choroidal, and scleral coloboma. Microscopically, the cyst connected to the coloboma consisted of an outer layer of fibrovascular tissue and an inner gliotic neuroectodermal layer. The treatment consisted of excision of cyst alone or of microphthalmic eye with cyst. The use of conformers was mandatory after removal of cystic eyeball for near normal development of both orbits to maintain facial symmetry in our paediatric patients. PMID- 8005650 TI - Post-penetrating keratoplasty glaucoma. AB - To study the risk factors in the development of glaucoma following penetrating keratoplasty, we retrospectively analysed 190 eyes of 185 consecutive patients who had undergone surgery during 1990. The donor button was larger by 0.2 mm and 0.5 mm in phakia and aphakia/pseudophakia patients, respectively. Over a mean follow-up period of 14.5 months, 52 of the 190 eyes (27.4%) either developed glaucoma de novo or had worsening of preexisting glaucoma. Of these 52 eyes, 38 were managed medically and 14 required surgery. From our study, aphakia (37%), pseudophakia (24%), preexisting glaucoma (81.8%), and regrafting (43.18%) were found to be the significant risk factors in the development of glaucoma following penetrating keratoplasty. PMID- 8005651 TI - Incidence of complications following 5-fluorouracil with trabeculectomies. AB - To investigate the incidence of complications reportedly caused by the use of 5 fluorouracil (5-FU) in glaucoma filtering surgery, we performed trabeculectomy with 5-FU on 57 eyes of 56 patients with advanced glaucoma. The mean preoperative intraocular pressure was 34.8 mm Hg. The most frequent complication encountered was superficial punctate keratopathy (26%), followed by shallowing of the anterior chamber (12%), choroidal detachment (9%), and flap retraction (7%). We, however, did not encounter any cases of confluent corneal epithelial defect, subepithelial scarring, or striate melanokeratosis which are usually described with the use of 5-FU. With a mean follow-up of 7.1 months, an intraocular pressure less than 16 mm Hg without hypotensive therapy were achieved in 73.7% of cases, and less than 21 mm Hg without hypotensive therapy in 86%. Considering the low incidence of complications and the high success rate, we recommend the use of 5-FU in routine glaucoma filtering surgery. PMID- 8005652 TI - Acanthamoeba keratitis in hard contact lens wearer. PMID- 8005653 TI - Subconjunctival Cysticercus cellulosae. PMID- 8005654 TI - Nasal septal chondrosarcoma with visual loss. PMID- 8005655 TI - Ichthyosis-associated spheroid corneal degeneration in HLA-DR identical brothers. PMID- 8005656 TI - Extracapsular cataract extraction: surgical techniques. PMID- 8005657 TI - A 9.0-kilobase-pair circular plasmid of Borrelia burgdorferi encodes an exported protein: evidence for expression only during infection. AB - In this study, we report the cloning, sequencing, and molecular analysis of a gene located on a 9.0-kbp circular plasmid of virulent Borrelia burgdorferi B31 designated eppA (exported plasmid protein A). This gene encodes a precursor protein of 174 amino acids including a signal peptide of 20 amino acids and a type I signal peptidase cleavage site. The mature EppA protein of 154 amino acids has a calculated molecular weight of 17,972. Several lines of evidence suggest that eppA is not expressed by B. burgdorferi B31 during in vitro cultivation. Immunoblot analysis using hyperimmune rabbit antiserum to recombinant EppA (rEppA) did not detect the presence of EppA in B. burgdorferi B31 cultivated in vitro. Northern blot analysis using total RNA isolated from in vitro-cultivated virulent B. burgdorferi B31 failed to detect an eppA transcript. EppA was not detected in culture supernatants of virulent B. burgdorferi B31 in a sensitive antigen-capture enzyme-linked immunosorbent assay. In contrast, evidence for expression of eppA during infection was based on the observation that patients with Lyme disease as well as rabbits experimentally infected with B. burgdorferi B31 produced antibodies that recognized rEppA. Because the cellular location of EppA in B. burgdorferi cannot be determined in vivo because of very small numbers of organisms present in vertebrate infection, we examined the cellular location of rEppA expressed in Escherichia coli. In E. coli, rEppA is targeted to the outer membrane. In addition, purified E. coli outer membranes containing rEppA treated with chaotrophic agents did not result in rEppA release. These findings are consistent with the idea that EppA is not peripherally associated with the outer membrane of E. coli but rather has an integral outer membrane association. PMID- 8005658 TI - Comparison of the sensitivities of Salmonella typhimurium oxyR and katG mutants to killing by human neutrophils. AB - The respiratory burst of neutrophils is believed to kill bacteria by generating oxidative species, such as superoxide anion, hydrogen peroxide, and oxidized halogen species. The oxyR gene of Salmonella typhimurium controls a regulon induced by oxidative stress, such as exposure to hydrogen peroxide. Some researchers have suggested that oxyR may play a key role in bacterial survival following phagocytosis. We have tested this possibility by comparing the survival, following exposure to human neutrophils, of isogenic strains bearing different oxyR alleles. Neither inactivation of the oxyR gene nor constitutive overexpression of the oxyR-regulated proteins (oxyR1 allele) greatly alters bacterial resistance to neutrophils. The katG gene, encoding the oxyR-regulated enzyme hydroperoxidase I, was also without effect on survival following exposure to neutrophils. We conclude that the oxyR response does not play a significant role in the resistance of S. typhimurium to phagocytic killing in vitro. PMID- 8005659 TI - The Vibrio cholerae toxin-coregulated-pilus gene tcpI encodes a homolog of methyl accepting chemotaxis proteins. AB - Virulence gene activation in Vibrio cholerae is under the control of the ToxR ToxT regulatory cascade. The ToxR regulon consists of genes required for toxin coregulated-pilus (TCP) biogenesis, accessory colonization factor genes, cholera toxin genes, and ToxR-activated genes (tag) of unknown function. The tagB gene was isolated by using a tagB::TnphoA fusion junction to probe a V. cholerae )395 bacteriophage lambda library. Nucleotide sequence analysis revealed that tagB is identical to tcpI, a gene which encodes a protein that negatively regulates the synthesis of the major pilin subunit of TCP (TcpA). Our results show that the tcpI gene encodes a 620-amino-acid protein that shares extensive sequence similarity with the highly conserved signaling domain in methyl-accepting chemotaxis proteins. Expression of tcpI in Escherichia coli results in the synthesis of a 71-kDa polypeptide that becomes localized to the inner membrane. Similarly, TcpI-PhoA alkaline phosphatase activity is enriched in V. cholerae inner membrane preparations. Colonies of V. cholerae tcpI::TnphoA mutant cells display increased swarming on solid media when compared with those of the parental V. cholerae O395. Taken together, these observations suggest that TcpI may play a dual role in promoting vibrio colonization of the small bowel. In response to the appropriate environmental signal(s), TcpI permits maximum expression of tcpA while simultaneously reducing vibrio chemotaxis-directed motility. We believe coordinate regulation of colonization and motility determinants, in such a fashion, facilitates efficient V. cholerae microcolony formation. PMID- 8005660 TI - Genetic, enzymatic, and pathogenic studies of the iron superoxide dismutase of Campylobacter jejuni. AB - Campylobacter jejuni is a microaerobic bacterium that produces an acute, self limiting, watery or bloody diarrhea in humans. Little is known about how C. jejuni causes disease or even what specific capabilities it requires for survival in vivo. The enzyme, superoxide dismutase (SOD), which catalyzes the breakdown of superoxide radicals to hydrogen peroxide and dioxygen is one of the bacterial cell's major defense mechanisms against oxidative damage. A PCR-based search for sod genes in C. jejuni 81-176 revealed that this bacterium contained at least one sod gene. We cloned and sequenced a sod gene from 81-176 and determined that its predicted protein product was most similar to that of FeSODs (sodB genes). Transcriptional analysis indicated that this gene is monocistronic and may be transcribed from a sigma 70-like promoter. Nondenaturing polyacrylamide gels stained to reveal SOD activities, accompanied by inhibition studies, demonstrated that C. jejuni produces five electrophoretically distinct bands of SOD activity, all of which appeared to be FeSODs. Analysis of an 81-176 sodB strain revealed that all of these FeSOD activities may be products of the one sodB gene that we cloned. The expression and enzymatic activity of the respective sodB and FeSOD produced by both C. jejuni and Helicobacter pylori were examined in Escherichia coli. Both genes were expressed in E. coli, and the proteins produced were enzymatically active. Finally, the ability of the 81-176 sodB strain to survive INT407 cell invasion was found to be significantly decreased (12-fold) compared with that of the parent, suggesting a potential role for SodB in C. jejuni intracellular survival. PMID- 8005661 TI - Adenovirus infection enhances in vitro adherence of Streptococcus pneumoniae. AB - Viruses are thought to facilitate bacterial infections of the respiratory tract, but the mechanisms are poorly understood. The present study analyzed the effect of adenovirus on bacterial adherence to human respiratory tract epithelial cells. The human lung carcinoma cell line A549 was infected with adenovirus of types 1, 2, 3, 4, 5, and 9. At a multiplicity of infection of 75 particles per cell, cytopathic effects occurred in 75 to 100% of the cells within 48 h. The virus infected cells were harvested at various times after infection and analyzed for the ability to bind strains of Haemophilus influenzae and Streptococcus pneumoniae. Adenovirus (types 1, 2, 3, and 5) commonly causing respiratory tract infections increased the binding of adherent S. pneumoniae strains to the cells. This effect was not seen for other adenovirus types. Adenovirus infection did not change the adherence of cells of poorly adhering strains of S. pneumoniae or H. influenzae. The increase in adherence of S. pneumoniae could be inhibited by the DNA synthesis inhibitor cytosine arabinofuranoside, which is known to block the late phase of the adenovirus infection. When electron microscopy was used, there was no evidence that virus particles bound directly to bacteria. Adherence was not affected by pretreatment of the cells with virus particles or viral proteins. This suggested that adenovirus infection upregulated receptors for S. pneumoniae. The increased attachment may be one mechanism by which viruses precondition the respiratory mucosa for bacterial infection. PMID- 8005662 TI - Bactericidal activity of synthetic peptides based on the structure of the 55 kilodalton bactericidal protein from human neutrophils. AB - Short (10- to 11-mer) hydrophilic peptides based on the structure of the 55-kDa bactericidal protein (BP55, B/PI, and CAP57) from human neutrophil granules were identified from the hydropathy plot of the 456-amino-acid sequence predicted from the nucleotide sequences of cDNA clones for BP55 and B/PI. Peptides corresponding to amino acid residues 90 to 99 (peptide #90-99), 86 to 99, or 90 to 102 of BP55 were bactericidal toward 5 x 10(6) Pseudomonas aeruginosa cells at 0.6 x 10(-5) to 1.5 x 10(-5) M and killed an Escherichia coli rough strain at 3 x 10(-5) M. The #90-99 peptide with a cysteine added at the amino terminus (C#90-99) was approximately 10 times more active than #90-99, killing P. aeruginosa at 1.5 x 10(-6) M. Peptides representing amino acid residues 27 to 37, 118 to 127, and 160 to 170 and the first 10 amino acids of the signal sequence for BP55 were not bactericidal. When coupled to either keyhole limpet hemocyanin or ovalbumin protein carriers through the thiol group, the C#90-99 peptide was not diminished on a molar basis in its capacity for killing of P. aeruginosa. Two other relatively hydrophilic peptides with an added amino-terminal cysteine, peptides C#227-236 and C#418-427, were not bactericidal at 1.2 x 10(-4) M or at 100 times the effective bactericidal concentration of C#90-99. The C#90-99 peptide killed E. coli at 1.5 x 10(-5) M, or at 10 times the concentration required to kill an equal number of P. aeruginosa cells. Although Pseudomonas cepacia and Staphylococcus aureus were resistent to killing by the parent BP55 molecule, they were susceptible to the C#90-99 and #90-99 peptides in the same concentration range as was E. coli. When all peptides were compared for the ability to neutralize E. coli O55:B5 endotoxin in a Limulus amoebocyte lysate assay, the C#227-236, C#418-427, and #160-170 peptides completely inhibited gelation at a 10(-4) M concentration. All other synthetic peptides, including bactericidal peptide #90-99 and its congeners, lacked endotoxin-neutralizing activity at the highest concentration tested (4.5 x 10(-4) M). A hybrid of the C#227-236 and #90 99 peptides (CHybrid) was identical to the C#227-236 peptide component in effectiveness for carrying out endotoxin neutralization and was fivefold better than the #90-99 peptide in its capacity for killing P. aeruginosa. PMID- 8005663 TI - Listeria monocytogenes infection enhances transcription factor NF-kappa B in P388D1 macrophage-like cells. AB - In the present study, we investigated the effect of Listeria monocytogenes infection on the cellular level of the transcription factors NF-kappa B, AP-1, and NF-IL6 in the macrophage-like cell line P388D1 by using electrophoretic mobility shift assays. Infection with L. monocytogenes enhanced the formation of two NF-kappa B-like DNA-protein complexes, C1 and C2, whereas the concentration of AP-1 and NF-IL6 complexes remained unaffected. In supershift assays using NF kappa B-specific antibodies, complex C2 was identified to be a p50 homodimer (KBF1) and complex C1 was identified as a p50/p65 heterodimer. Both complexes were formed within 10 min after addition of the bacteria. Since the synthesis of tumor necrosis factor alpha and interleukin-1 occurs at later times, these cytokines cannot be the mediators of enhanced NF-kappa B formation. Infection experiments with different nonhemolytic mutants of L. monocytogenes and the use of the phagocytosis inhibitor cytochalasin B suggest that events prior to invasion and escape of the bacteria from the phagosome into the cytoplasm enhance the nuclear transport of p50/p65 NF-kappa B components. PMID- 8005664 TI - Induction of tumor necrosis factor alpha by the group- and type-specific polysaccharides from type III group B streptococci. AB - Previous studies suggested that circulating tumor necrosis factor alpha (TNF alpha) may have a pathophysiologic role in experimental neonatal sepsis induced by group B streptococci (GBS). This study was undertaken to investigate the ability of the type III and group-specific polysaccharides of GBS to induce TNF alpha production and TNF-alpha-dependent lethality in neonatal rats. The cytokine was detected in plasma samples by the L929 cytotoxicity assay. Intracardiac injections of either polysaccharide induced dose-dependent, transient elevations in plasma TNF-alpha levels that returned to baseline values after 5 h. The group specific antigen induced significantly higher mean peak TNF-alpha levels than the type III antigen (125 +/- 47 versus 44 +/- 15 U/ml with 70 mg/kg of body weight). Glycogen (70 mg/kg), used as a negative control, did not induce TNF-alpha. The lipopolysaccharide-neutralizing agent polymyxin B did not decrease TNF-alpha levels induced by either polysaccharide, ruling out contamination with endotoxin as a possible cause of TNF-alpha induction. Fifty percent lethal doses of the type III and group-specific antigens given as intracardiac injections were 105 and 16 mg/kg, respectively. Salmonella endotoxin, used as a positive control, had a 50% lethal dose of 0.1 mg/kg. The lethal activities of GBS polysaccharides, as well as endotoxin, were completely prevented by pretreatment of neonatal rats with the respective specific antibodies or anti-murine TNF-alpha serum. To assess the relative importance of the type-specific substance in TNF-alpha induction by whole bacteria, two unrelated GBS transposon mutants devoid of only the type specific capsular polysaccharide (COH1-13 and COH31-15) were employed. Each of the heat-killed unencapsulated mutants was able to produce plasma TNF-alpha level elevations or TNF-alpha-dependent lethality but was significantly less efficient in these activities than the corresponding encapsulated wild-type strain. These data suggest that the presence of type-specific material on GBS is not necessary for the stimulation of TNF-alpha production. Type III capsular polysaccharide, however, can significantly increase the ability of GBS to induce TNF-alpha. Further studies will be needed to assess the importance of TNF-alpha induction by the group- and type-specific antigens in the pathophysiology of GBS disease. PMID- 8005665 TI - Immune responses of young mice to pneumococcal type 9V polysaccharide-tetanus toxoid conjugate. AB - Pneumococcal type 9V polysaccharide (PS), contained in the current pneumococcal vaccine, induces only a weak antibody response in young children and therefore is not an effective vaccine for young children. To increase its immunogenicity, a conjugate of PS to a protein carrier, tetanus toxoid (TT), was prepared. To quantify the immune response, mouse anti-9V PS immunoglobulin G (IgG) and IgM reference standards were established. Young mice immunized at 2 weeks of age produced IgM antibody in response to 9V PS alone or 9V PS conjugated to TT. However, only the 9V PS-TT conjugate induced an IgG antibody response and an anamnestic effect. Thus, a covalent linkage between TT and 9V PS was required for isotype switching from IgM to IgG. 9V PS-TT adsorbed with aluminum hydroxide adjuvant resulted in a fivefold or greater increase in the IgG antibody level. We also studied the effect of maternal immunization on the immune response of young mice to 9V PS-TT. Maternal immunization before mating or before mating and during gestation primed 2-week-old progeny given two injections of 9V PS-TT to produce more IgM antibody than progeny from unimmunized mothers. The IgG antibody level of neonates at birth was similar to that observed in the mothers and was probably passive antibody. These results indicate that maternal immunization with an optimum dose of a PS-protein conjugate before and/or during pregnancy, followed by immunization of the offspring with the conjugate, could provide young children with an enhanced IgM antibody response to pneumococcal PSs. PMID- 8005666 TI - Tumor necrosis factor alpha has a protective role in a murine model of systemic candidiasis. AB - The role of tumor necrosis factor alpha (TNF-alpha) in host defense against systemic Candida albicans infection was evaluated in a murine model of systemic candidiasis in which uniform death occurred between 5 and 6 days after infection. TNF-alpha was first detected at 16 h postinfection and progressively increased thereafter. Peak levels (700 to 900 pg/ml) were measured in mice near death. Administration of 0.5 to 1.0 mg of polyclonal immunoglobulin G (IgG) TNF-alpha antibody (TNF-alpha Ab) to mice 2 h preinfection neutralized serum TNF-alpha for up to 30 h. However, this regimen shortened survival from a mean of 5.5 days for IgG controls to 3.4 days (P = 1.9 x 10(-12)). Semiquantitative cultures of spleen, lung, liver, and kidney conducted at 1, 2, and 3 days postinfection found colony counts of spleen and kidney to be significantly higher for TNF-alpha Ab recipients but only for the first 48 h. Administration of 1.5 and 1.0 mg of TNF alpha Ab at 2 h before and 48 h after fungal injection, respectively, shortened the mean survival from 4.9 to 2.3 days (P = 5.2 x 10(-8)). This regimen neutralized serum TNF-alpha throughout infection. With this regimen, colony counts of all organs were significantly higher in TNF-alpha Ab recipients at 1, 2, and 3 days postinfection. Histopathologic studies showed an increase in the number and size of C. albicans foci in tissues. Peripheral leukocyte counts and inflammatory response in tissue were similar for TNF-alpha Ab and IgG sham recipients. In vitro, incubation of C. albicans with four to eight times the peak serum levels of TNF-alpha for up to 24 h did not inhibit the rate of germ tube or pseudohypha formation. Thus, TNF-alpha that was produced during infection with C. albicans augmented host resistance against this organism and prolonged survival. The protective effect of TNF-alpha was not mediated by increased leukocytes in blood or tissues nor by a direct anticandidal effect of TNF-alpha. This study suggests that the administration of exogenous TNF-alpha may enhance host resistance against systemic C. albicans infection and may improve host survival. PMID- 8005667 TI - Antibody against interleukin-6 reduces inflammation and numbers of cysts in brains of mice with toxoplasmic encephalitis. AB - Treatment of toxoplasmic encephalitis in C57BL/6 mice with monoclonal antibody (MAb) against interleukin-6 (IL-6) resulted in a remarkable decrease in the number of foci of acute inflammation in their brains caused by proliferation of tachyzoites. In brains of mice treated with isotype control MAb and those treated with anti-IL-6 MAb, tachyzoites were observed only in foci of acute inflammation. Immunoperoxidase staining revealed a greatly diminished frequency of tachyzoites in brains of mice treated with anti-IL-6 MAb. Of interest, treatment with MAb against IL-6 was also associated with reduced numbers of Toxoplasma gondii cysts in the brains and with higher serum levels of gamma interferon than in control mice. Paradoxically, the mice treated with anti-IL-6 MAb had higher serum levels of IL-6 as measured by an enzyme-linked immunosorbent assay than controls. These results revealed the importance of IL-6 in the immunopathogenesis of murine toxoplasmic encephalitis. PMID- 8005668 TI - Neutrophils are critical for host defense against primary infection with the facultative intracellular bacterium Francisella tularensis in mice and participate in defense against reinfection. AB - It is generally believed that immunity to experimental infection with the facultative intracellular bacterium Francisella tularensis is an example of T cell-mediated immunity that is expressed by activated macrophages and mediated by Francisella-specific T cells. According to the results presented herein, neutrophils are also essential for defense against primary infection with this organism. It is shown that mice depleted of neutrophils by treatment with the granulocyte-specific monoclonal antibody RB6-8C5 are rendered defenseless against otherwise sublethal doses of F. tularensis LVS inoculated intravenously or intradermally. In neutrophil-depleted mice, the organism grew progressively in the livers, spleens, and lungs to reach lethal numbers, whereas infection was resolved in normal mice. Although neutrophils were found to resistance to reinfection, their participation was less important. The results suggest that neutrophils are needed for defense against primary infection because they serve to restrict the growth of F. tularensis before it reaches numbers capable of overwhelming a developing specific immune response. The exact way that neutrophils achieve this is not clear at this time, although it is probable that they contribute in ways other than by ingesting and killing the bacterium. PMID- 8005669 TI - A family of surface-exposed proteins of 20 kilodaltons in the genus Borrelia. AB - Relapsing fever and Lyme disease spirochetes of the genus Borrelia display at their surfaces abundant lipoproteins: Vmp proteins in Borrelia hermsii and Osp proteins in Borrelia burgdorferi. Vmp and Osp proteins largely determine serotype specificity, and neutralizing antibodies of infected or immunized animals are directed at them. For the present study, we examined B. hermsii serotype 33, which is unique among strain HS1 serotypes in the low frequency of switches to other serotypes during infections and in vitro cultivation. Failing to clone the complete vmp33 gene, we accomplished its further characterization by (i) determining three partial amino acid sequences, (ii) designing oligonucleotide primers based on these amino acid sequences, (iii) cloning and sequencing the central portion of vmp33, and (iv) using outwardly directed primers and the inverse PCR to clone the 5' and 3' ends of the gene and flanking regions. The transcriptional start site was identified by primer extension analysis. Vmp33 was a polypeptide of 211 amino acids; the three partial amino acid sequences were identified in the open reading frame. Vmp33 was found to be more similar to other 20-kDa Vmp proteins of B. hermsii and to OspC proteins of B. burgdorferi than it was to 35- to 39-kDa Vmp proteins of the same strain. Moreover, OspC proteins were more similar to Vmp33 than they were to OspA, -B, or -D proteins of B. burgdorferi. These sequence similarities were consistent with Western blot (immunoblot) findings of cross-reactions between Vmp33 and OspC with anti-Vmp33 and anti-OspC sera. The promoter for the expressed vmp33 gene was found to be different from the expression site for other active vmp genes characterized to date. These results indicate that Vmp33 and other small Vmp's belong with OspC to a genus-wide family of 20-kDa proteins and that expression of these proteins may be coordinated with expression of other Vmp and Osp proteins in Borrelia spp. PMID- 8005670 TI - Affinity of the C9 molecule for the C5b-8 complex compared with that for the complex containing C9 molecules. AB - Gram-negative bacterial cells exposed to a complement source may carry membrane attack complexes containing variable numbers of C9 molecules per C5b-8 site. In order to investigate the assembly of this complex, the ability of C9 molecules to bind to C5b-8 complexes was compared with the binding characteristics of C9 for C5b-8 complexes containing variable numbers of bound C9 molecules. The apparent dissociation constant (Kd) of the C9 molecule for the C5b-8 site on a complement sensitive strain of Escherichia coli was 1.2 (+/- 0.15) nM at 0 degree C. These conditions allow the binding of one C9 molecule per C5b-8 site. The C5b-8 site containing one C9 molecule bound a second C9 molecule at 0 degree C only after incubation at 37 degrees C. The binding of C9 to a C5b-8 site containing one C9 molecule was found to be 1.3 (+/- 0.2) nM. Therefore, the presence of a C9 molecule did not significantly alter the binding capacity of the C5b-8 site for additional C9 molecules. A similar result was obtained by using rabbit erythrocytes bearing either C5b-8 sites or C5b-8 sites containing one molecule of C9 per complex at 0 degree C. The similarity of binding characteristics for the first and second C9 molecules argues that the initial C9 molecule in the complex does not affect the binding of subsequent C9 molecules. This suggests that a unique C9 binding site that does not involve previously bound C9 molecules may exist on the forming membrane attack complex. PMID- 8005671 TI - Presence of a capsule in Erysipelothrix rhusiopathiae and its relationship to virulence for mice. AB - Three avirulent insertional mutants of Erysipelothrix rhusiopathiae were obtained by the technique of transposon mutagenesis with the self-conjugative transposon Tn916. The interactions between murine polymorphonuclear leukocytes and parent and mutant strains were studied in vitro. In the presence of normal serum, the virulent parent strain was resistant to phagocytosis, whereas the avirulent mutant strains were efficiently phagocytosed. In the presence of immune serum, the parent and the mutant strains were both efficiently phagocytosed. Electron microscopic examination of the parent strain demonstrated the presence of a structure resembling a capsule which was absent on the mutant strains, suggesting that a capsule may be involved in virulence. This was confirmed in studies in which an avirulent mutant strain reverted to virulence following acquisition of a capsule when the transposon was lost by spontaneous excision. These results strongly suggest that virulence of E. rhusiopathiae is associated, at least in part, with resistance to phagocytosis by polymorphonuclear leukocytes and that this antiphagocytic ability of the bacterium results from its possession of a capsule. PMID- 8005672 TI - Development of destructive arthritis in vaccinated hamsters challenged with Borrelia burgdorferi. AB - We present the first direct evidence that adverse effects, particularly severe destructive arthritis, can develop in vaccinated hamsters after challenge with Borrelia burgdorferi sensu lato isolates. Hamsters were vaccinated with a whole cell preparation of Formalin-inactivated B. burgdorferi sensu stricto isolate C-1 11 in adjuvant. A severe destructive arthritis was readily evoked in vaccinated hamsters challenged with the homologous B. burgdorferi sensu stricto isolate C-1 11 before high levels of protective borreliacidal antibody developed. Once high levels of C-1-11 borreliacidal antibody developed, hamsters were protected from homologous challenge and development of arthritis. Vaccinated hamsters, however, still developed severe destructive arthritis when challenged with other isolates of the three genomic groups of B. burgdorferi sensu lato (B. burgdorferi sensu stricto isolate 297, Borrelia garinii isolate LV4, and Borrelia afzelii isolate BV1) despite high levels of C-1-11 specific borreliacidal antibody. Vaccines that contained whole spirochetes in adjuvant induced destructive arthritis, but this effect was not dependent on the isolate of B. burgdorferi sensu lato or the type of adjuvant. These studies demonstrate that caution is necessary when employing whole spirochetes in adjuvant for vaccination to prevent Lyme borreliosis. Additional studies are needed to identify the antigen(s) responsible for the induction and activation of arthritis and to define the immune mechanisms involved. PMID- 8005674 TI - Fimbria-mediated adherence of Candida albicans to glycosphingolipid receptors on human buccal epithelial cells. AB - Candida albicans is an opportunist fungal pathogen that has the ability to adhere to host cell surface receptors via a number of adhesins. Yu et al. (L. Yu, K. K. Lee, K. Ens, P. C. Doig, M. R. Carpenter, W. Staddon, R. S. Hodges, W. Paranchych, and R. T. Irvin, Infect. Immun. 62:2834-2842, 1994) described the purification and initial characterization of a fimbrial adhesin from C. albicans. In this paper, we show that C. albicans fimbriae also bind to asialo-GM1 [gangliotetraosylceramide: beta Gal(1-3)beta GalNAc(1-4) beta Gal(1-4)beta Glc(1 1)Cer] immobilized on microtiter plates in a saturable and concentration dependent manner. C. albicans fimbrial binding to exfoliated human buccal epithelial cells (BECs) was inhibited by asialo-GM1 in in vitro binding assays. The fimbriae interact with the glycosphingolipid receptors via the carbohydrate portion of the receptors, since fimbriae were observed to bind to synthetic beta GalNAc(1-4)beta Gal-protein conjugates and the disaccharide was able to inhibit binding of fimbriae to BECs in in vitro binding assays. We conclude from these results that the C. albicans yeast form expresses a fimbrial adhesin that binds to glycosphingolipids displayed on the surface of human BECs. PMID- 8005673 TI - Partial characterization of a Candida albicans fimbrial adhesin. AB - Candida albicans is the primary etiologic agent of candidiasis, a disease that can vary from superficial mucosal lesions to life-threatening systemic or disseminated diseases. Strains of C. albicans have been reported to possess long, thin filamentous protein cell surface appendages termed fimbriae (R.B. Gardiner, M. Canton, and A. W. Day, Bot. Gaz. 143:534-541, 1982). These fimbriae were isolated, purified, and partially characterized. The major structural subunit of the fimbriae is a glycoprotein which consists of 80 to 85% carbohydrate (consisting primarily of D-mannose) and 10 to 15% protein. The molecular weight of the glycosylated fimbrial subunit is approximately 66,000, while unglycosylated protein has an approximate molecular weight of 8,644. The fimbriae function as adhesins mediating C. albicans binding to human buccal epithelial cells. Amino acid analysis of the purified fimbrial subunit indicates that the fimbrial subunit is composed of 50% hydrophobic amino acid residues. The N terminus of the fimbrial subunit is blocked to N-terminal sequencing. PMID- 8005675 TI - Cloning of a Cryptococcus neoformans gene, GPA1, encoding a G-protein alpha subunit homolog. AB - We have isolated a gene, GPA1, from Cryptococcus neoformans by the PCR technique. DNA sequencing of the GPA1 clone suggested that it encodes a protein homologous to the G-protein alpha-subunit family. Comparison of the deduced amino acid sequence of the GPA1-encoded protein revealed that it is about 45% identical to several mammalian Gi alpha subunits and 48% identical to the G alpha protein Gpa2 from Saccharomyces cerevisiae. G alpha proteins are known to be involved in mating of other yeasts, such as S. cerevisiae and Schizosaccharomyces pombe. Southern analysis demonstrated that GPA1 is present in a single copy within the Cryptococcus genome. Isolation of the cDNA for GPA1 confirmed that the gene contains six introns within the coding region. The GPA1 transcript was identified by Northern (RNA) analysis as a 1.6-kb RNA present in exponentially growing cells of both the alpha and a mating types. Moreover, the abundance of this transcript increased in cells shifted to starvation medium. Coincubation of alpha and a cells on starvation medium is required for mating of cryptococcal cells. Thus, our results are consistent with the involvement of C. neoformans GPA1 in mating. PMID- 8005676 TI - Occurrences, immunoglobulin classes, and biological activities of antibodies in normal human serum that are reactive with Cryptococcus neoformans glucuronoxylomannan. AB - Serum obtained from normal human subjects contains antibodies reactive in an enzyme-linked immunosorbent assay with the glucuronoxylomannan (GXM) of Cryptococcus neoformans. The frequency of occurrence of class-specific antibodies among normal subjects was 28% for immunoglobulin G (IgG), 98% for IgM, and 3% for IgA. Anti-GXM antibodies with kappa light chains occurred in 98% of normal subjects, while the occurrence of lambda light chains was 28%. Each of five subjects with high levels of anti-GXM IgG antibodies had readily detectable antibodies of the IgG2 isotype; two of the five subjects had readily detectable IgG1 antibody. An examination of sera from human immunodeficiency virus-infected patients showed that human immunodeficiency virus infection was accompanied by a significant decrease in the occurrence of IgM antibodies and anti-GXM antibodies with kappa light chains; these decreases occurred early in infection when CD4 counts were still > or = 500 cells per microliter. A slight but not statistically significant decrease in the occurrence of anti-GXM IgG antibodies was seen only in patients with CD4 levels of < 200 cells per microliter. Sera from normal subjects with high levels of anti-GXM IgG antibodies were examined to identify any contribution of the antibodies to complement activation or to opsonization of the yeast cells. An analysis of the kinetics for activation and binding of C3 to the yeast cell showed no pattern of quantitative or qualitative differences between sera with high or low levels of anti-GXM IgG antibodies. Phagocytosis studies showed that the naturally occurring IgG antibodies did not contribute to opsonization of the yeast cells. PMID- 8005677 TI - Self-transmissible R plasmids encoding CS31A among human Escherichia coli strains isolated from diarrheal stools. AB - The CS31A antigen was first described for septicemic and enterotoxigenic bovine E. coli strains. In our study, of 597 human Escherichia coli strains isolated from diarrheagenic stools of hospitalized patients, 30 (5%) hybridized with the CS31A DNA probe. These CS31A-positive E. coli strains diffusely adhered to Caco-2 and/or HEp-2 cells and produced a major surface protein of either 30 or 30.5 kDa according to the strain. These proteins were antigenically related to the two forms of the CS31A antigen, namely, CS31A-L and CS31A-H. Genes encoding CS31A were located on 140-kb conjugative R plasmids. E. coli transconjugants expressed major surface proteins similar to those of the wild-type strains and adhered to Caco-2 and/or HEp-2 cells. An association of CS31A and another adhesive factor of the Dr family was found in 70% of wild-type strains, since 21 strains hybridized with the diffuse adhesion DNA probe corresponding to the accessory gene (daaC) of the F1845 adhesin. Comparison of the restriction patterns of the 140-kb R plasmids of the CS31A-positive E. coli strains showed these plasmids to be similar. Hybridization experiments indicated that the genes encoding CS31A and resistance to penicillin were located together on either of two 20- or 27-kb EcoRI restriction fragments in four E. coli strains. We reported a similar linkage between these genes in Klebsiella pneumoniae strains which produced CF29K, a CS31A-like antigen. These results suggest a horizontal transfer between E. coli and K. pneumoniae strains. PMID- 8005678 TI - Binding and accumulation of hemin in Porphyromonas gingivalis are induced by hemin. AB - Although hemin is an essential nutrient for the black-pigmented oral bacterium Porphyromonas gingivalis, the mechanisms involved in hemin binding and uptake are poorly defined. In this study, we have examined the binding of hemin and Congo red (CR) to P. gingivalis whole cells and have defined the conditions for maximal binding. Additionally, the accumulation of hemin by P. gingivalis under growing conditions has been characterized. P. gingivalis A7436 was grown under hemin- or iron-deplete conditions (basal medium [BM] or Schaedler broth with dipyridyl [SBD]) or under hemin- or iron-replete conditions (BM with hemin [BMH] or Schaedler broth [SB]), and hemin and CR binding were assessed spectrophotometrically. Binding of hemin by P. gingivalis whole cells was rapid and was observed in samples obtained from cells grown under hemin- and iron replete and hemin-deplete conditions but was not observed in cells grown under iron limitation. We also found that P. gingivalis whole cells bound more hemin when grown in BMH or SB than cells grown in BM or SBD. Binding of CR by P. gingivalis A7436 was also enhanced when cells were grown in the presence of hemin or when cells were incubated with hemin prior to CR binding. Hemin binding and accumulation were also assessed using [14C]hemin and [59Fe]hemin under growing conditions. Both [14C]hemin and [59Fe]hemin were accumulated by P. gingivalis, indicating that iron and the porphyrin ring were taken into the cell. Binding and accumulation of hemin under growing conditions were also induced by growth of P. gingivalis in hemin-replete media. Hemin accumulation was inhibited by the addition of KCN to P. gingivalis cultures, indicating that active transport was required for hemin uptake. [14C]hemin binding and accumulation were also inhibited by the addition of either cold hemin or protoporphyrin IX. Taken together, these results indicate that P. gingivalis transports the entire hemin moiety into the cell and that the binding and accumulation of hemin are induced by growth of cultures in the presence of hemin. PMID- 8005681 TI - Intermolecular relationships of major surface proteins of Anaplasma marginale. AB - Immunization with Anaplasma marginale membranes containing major surface proteins (MSPs) induces protective immunity against clinical disease (N. Tebele, T. C. McGuire, and G. H. Palmer, Infect. Immun. 59:3199-3204, 1991). For use in design of a recombinant antigen subunit vaccine for A. marginale, intermolecular relationships of known A. marginale MSPs were analyzed. Under nonreducing conditions, MSP-2 and MSP-5 occur as multimers. A large (> 300-kDa-molecular mass), nonreduced protein complex contained MSP-1a linked by disulfide bonds to MSP-1b and by noncovalent bonds to MSP-5. MSP-2 was also noncovalently bound to this complex. The nearest neighbor membrane proteins were identified by cross linking reactions followed by immunoblotting with anti-MSP antibodies. A cross linked aggregate retained in the stacking gel contained MSP-1a, MSP-1b, MSP-2, MSP-3, MSP-4, and MSP-5. Collectively, the data indicate that MSP-2 and MSP-5 occur as monomers and disulfide-bonded multimers. The MSP-1 complex occurs as both disulfide-bonded and noncovalently associated MSP-1 and MSP-1b, and MSP-2 and MSP-5 are noncovalently associated with MSP-1. Also, MSP-1, MSP-2, MSP-3, and MSP-4 are nearest neighbors, and MSP-5 is noncovalently associated with this cross-linked complex. PMID- 8005682 TI - Protein synthesis is required for expression of anthrax lethal toxin cytotoxicity. AB - Anthrax lethal toxin, which is composed of two proteins, i.e., protective antigen and lethal factor, is cytolytic to mouse peritoneal macrophages and the macrophage-like cell line J774A.1. After exposure of cells to lethal toxin, inhibition of protein synthesis occurred only slightly before the onset of cytolysis. Thus, cell death did not appear to be due to inhibition of protein synthesis. However, prior treatment of J774A.1 cells with cycloheximide or puromycin, which inhibited protein synthesis, protected them completely against lethal toxin-induced cytolysis, which suggested that continuous protein synthesis is required for the expression of lethal toxin activity. Inhibition of protein synthesis had no appreciable effect on the binding of protective antigen to the cell surface receptor or on proteolytic cleavage of surface-bound protective antigen. Furthermore, inhibition of protein synthesis did not alter the uptake of toxin, which suggested that protein synthesis is required at a later stage of the intoxication process. The protection provided by inhibition of protein synthesis was effective, even up to 1 h after exposure to anthrax lethal toxin. The increased uptake of calcium observed in cells exposed to lethal toxin did not occur when they were protected by blocking protein synthesis. Identifying the protein(s) synthesized during the intoxication process may help to understand the mechanism of cell death produced by anthrax lethal toxin. PMID- 8005680 TI - Actin accumulation associated with clustered and localized adherence in Escherichia coli isolated from patients with diarrhea. AB - Escherichia coli D2 (serotype 07:H-) that was isolated from a child with diarrhea hybridized with an F1845 DNA probe used to detect diffuse adherence. Strain D2 adhered to tissue culture cells (HeLa and HEp-2 cells) in a clustered pattern but did not autoagglutinate on the cell surface and induced the elongation of microvilli after 3 h of incubation. After 6 h of incubation, the infected cells were positive for fluorescent-actin staining at the site of clustered adherence. When analyzed with a confocal laser scanning microscope, each D2 cell was surrounded by accumulated actin in a capsule-like formation. Capsule-like, accumulated actin was also observed with enteropathogenic E. coli (EPEC), although in this case, actin accumulation was associated with EPEC microcolonies in a localized pattern. Four other strains of F1845 DNA probe-positive, diffusely adhering E. coli were negative for actin accumulation. Strain D2 did not hybridize with EPEC attaching and effacing DNA or EPEC adherence factor DNA probes. In addition, clustered D2 cells were found inside tissue culture cells. The data suggest a novel infectious mechanism as well as genetic heterogeneity of F1845 DNA probe-positive E. coli. Capsule-like, accumulated actin may protect the bacteria from host defense mechanisms. PMID- 8005679 TI - Impairment of the cellular immune response in acute murine toxoplasmosis: regulation of interleukin 2 production and macrophage-mediated inhibitory effects. AB - Depression of the cellular immune response to Toxoplasma gondii has been reported in both mice and humans. The present study was undertaken to determine the kinetics and mechanism of the observed downregulation of interleukin 2 (IL-2) production during experimental murine toxoplasmosis. For these investigations, the cell-mediated immune response to the wild type (PTg) was compared with that to the less-virulent mutant parasite (PTgB), which is deficient in the major surface antigen, p30 (SAG-1). Spleen cells from infected A/J mice failed to proliferate in response to Toxoplasma antigens during the first week of infection. Both PTg- and PTgB-infected A/J mice exhibited a significant reduction in the concanavalin A (Con A)-induced lymphoproliferative response. Further, the response of splenocytes from mice infected with the wild-type parasite was significantly diminished compared with that of mice infected with PTgB. The lymphoproliferative response to Con A reached its nadir at day 7 and remained below control levels for at least 14 days postinfection. By day 21 postinfection, the response to Con A and to Toxoplasma antigens was restored to the level observed prior to day 7. Con A-stimulated culture supernatants of spleen cells from mice on day 7 postinfection contained significantly less IL-2 than normal mice. There was no significant difference in the numbers of binding sites or capacity of high-affinity IL-2 receptors between infected and normal mouse splenocytes as determined by Scatchard analysis. Exogenous IL-2 at different concentrations failed to restore the proliferative response of lymphocytes from infected mice to Con A. Adherent macrophages from 7-day-infected mice were able to suppress IL-2 production by normal splenocytes following stimulation with Con A. The inhibitory activity mediated by infected cells was reversed by the antibody to IL-10 but not transforming growth factor beta. There were insignificant levels of nitric oxide production in both infected and normal splenocytes. These results indicate that during acute murine toxoplasmosis, there is a well-defined period (day 7) during which both the T-cell mitogen and parasite antigen-associated lymphoproliferative response are reduced. Further, there is a reduction in the production of IL-2 and an increase in IL-10, which appear to mediate, in part, the observed downregulation of immunity to T. gondii. PMID- 8005683 TI - Sera from chronic Chagasic patients and rodents infected with Trypanosoma cruzi inhibit trans-sialidase by recognizing its amino-terminal and catalytic domain. AB - We investigated whether sera from chronic Chagasic patients and animals infected with Trypanosoma cruzi inhibit the removal of sialic acid from human erythrocytes and the transfer of sialic acid from sialyllactose to [14C]lactose in the reactions catalyzed by the parasite trans-sialidase. Sera from Swiss mice and Calomys callosus animals infected with three different T. cruzi strains inhibit both reactions. Inhibition increases during the infection, reaching maximal levels when the parasitemia decreases. Among 44 sera of untreated chronic Chagasic patients, 40 inhibit both reactions. Inhibition is observed with total, defatted sera or with purified immunoglobulins. Whereas most of the inhibitory antibodies from Chagasic patients react with the papain fragment of trans sialidase in immunoblots, a few patients have noninhibitory antibodies that react only with the entire trans-sialidase. These findings may be relevant for the pathology of Chagas' disease. PMID- 8005684 TI - Complete protection against Plasmodium yoelii by adoptive transfer of a CD8+ cytotoxic T-cell clone recognizing sporozoite surface protein 2. AB - BALB/c mice immunized with irradiated Plasmodium yoelii sporozoites produce antibodies and cytotoxic T lymphocytes against the circumsporozoite protein and against a 140-kDa protein, sporozoite surface protein 2 (PySSP2). Approximately 50% of mice immunized with P815 cells transfected with the gene encoding PySSP2 are protected against malaria, and this protection is reversed by in vivo depletion of CD8+ T cells. To determine if CD8+ T cells against PySSP2 are adequate to protect against malaria in the absence of other malaria-specific immune responses, we produced three CD8+ T-cell clones by stimulating spleen cells from mice immunized with irradiated P. yoelii sporozoites with a mitomycin treated P815 cell clone transfected with the PySSP2 gene. Adoptive transfer of clone TSLB7 protected 100% of mice against P. yoelii. The second clone protected 58% of mice, and the third clone provided no protection. Clone TSLB7 protected even when administered 3 h after sporozoite inoculation at a time when sporozoites had entered hepatocytes, suggesting that it is recognizing and eliminating infected hepatocytes. These studies demonstrate that cytotoxic T lymphocytes against PySSP2 can protect against P. yoelii sporozoite challenge in the absence of other parasite-specific immune responses. PMID- 8005686 TI - Ferritin stimulation of a monokine inhibitor of lipopolysaccharide-augmented myelopoiesis is ferroxidase dependent. AB - Ferritin inhibition of myelopoiesis has been associated with intrinsic ferroxidase activity of heavy-chain ferritin and with production of a monokine inhibitor of lipopolysaccharide (LPS)-augmented monocytopoiesis. We report here that intrinsic ferroxidase activity of heavy-chain ferritin is required for stimulated production of the monokine inhibitor of LPS-augmented monocytopoiesis. PMID- 8005685 TI - Immune responses in humans and animals to meningococcal transferrin-binding proteins: implications for vaccine design. AB - The results reported here show that the two meningococcal transferrin-binding proteins (TBP1 and TBP2) generate different immune responses in different host species and that there is variation in response dependent on the method of antigen preparation and possibly the route of administration. Mice immunized with either whole cells of Neisseria meningitidis SD (B:15:P1.16) or the isolated TBP1 TBP2 complex from the same strain produced antisera which, when tested against a representative panel of meningococcal isolates by Western blotting (immunoblotting), recognized some but not all heterologous TBP2 molecules. In contrast, rabbit antisera raised to the same preparations were cross-reactive with almost all the TBP2 molecules. The immune response to TBP1 was also host species dependent. Western blot analysis with denatured TBP1 failed to detect antibodies in antisera raised in mice to whole cells or in a rabbit to the TBP1 TBP2 complex but detected broadly cross-reactive antibodies in mouse anti-TBP1 TBP2 complex sera and strain-specific antibodies in rabbit anti-whole-cell serum. Human convalescent-phase sera obtained from five patients infected with meningococci of different serogroups and serotypes contained fully cross-reactive antibodies to TBP2 but no anti-TBP1 antibodies, when examined on Western blots. However, on dot immunoblots, the same patients' sera, as well as the mouse anti whole cell and the rabbit anti-TBP1-TBP2 complex sera, reacted with purified biologically active TBP1 of strain SD. This indicates that native TBP1, a protein which loses its biological and some of its immunological activities when denatured, is immunogenic and that humans generate cross-reactive antibodies to native epitopes. These observations have important implications for assessing the vaccine potential of TBPs and other meningococcal antigens. Conclusions regarding the usefulness of TBPs as candidate components of meningococcal serogroup B vaccines based on results from certain animal species such as mice, or on methods such as Western blotting, may have little bearing on the situation in humans and may lead to some potentially useful antigens being disregarded. PMID- 8005687 TI - Growth temperature reversibly modulates the virulence of Legionella pneumophila. AB - In chemostat culture, the virulence of two strains of Legionella pneumophila was shown to be significantly (P < 0.05) reduced when the culture temperature was lowered from 37 to 24 degrees C. This modulation was reversed by returning the temperature to 37 degrees C, which resulted in a statistically significant (P < 0.05) increase in virulence. PMID- 8005688 TI - Unique ability of the Proteus mirabilis capsule to enhance mineral growth in infectious urinary calculi. AB - Struvite (MgNH4PO4.6H2O) calculi are a common complication of Proteus mirabilis urinary tract infections. Although urease is a major virulence factor in calculus formation, the polysaccharide capsule (CPS) of this organism also enhances struvite crystallization and growth in vitro (L. Clapham, R. J. C. McLean, J. C. Nickel, J. Downey, and J. W. Costerton, J. Crystal Growth 104:475-484, 1990). We obtained purified CPS, of known structure and varying anionic character, from P. mirabilis ATCC 49565 and several other organisms. Artificial urine was added to CPS, and the pH was elevated from 5.8 to 8.5 by the addition of urease or titration with 0.25 M NH4OH to induce struvite crystallization. Crystallization was measured by particle counting (Coulter counter), and the morphology (crystal habit) was examined by phase-contrast microscopy. In the presence of partially anionic P. mirabilis CPS, struvite formation occurred at a lower pH than in the absence of CPS or in the presence of other neutral, partially anionic, or anionic CPS. At pH 7.5 to 8.0, significantly more struvite crystals formed in the presence of P. mirabilis CPS than under other experimental conditions. With the exception of one polymer (curdlan) which did not bind Mg2+, enhancement of struvite formation by CPS polymers was inversely proportional to their Mg2+ binding ability. We speculate that the structure and partial anionic nature of P. mirabilis CPS enable it to enhance struvite formation by weakly concentrating Mg2+ ions during struvite crystal formation. This illustrates a new virulence aspect of bacterial CPS during infection. PMID- 8005689 TI - Susceptibility of melanized and nonmelanized Cryptococcus neoformans to nitrogen- and oxygen-derived oxidants. AB - Melanized Cryptococcus neoformans cells were less susceptible than nonmelanized cells to the fungicidal effects of nitrogen- and oxygen-derived oxidants. The results support the hypothesis that the phenoloxidase enzyme system contributes to virulence by protecting C. neoformans against nitrogen- and oxygen-derived oxidative antimicrobial molecules produced by immune effector cells. PMID- 8005690 TI - Epithelial cell invasion and survival of Bordetella bronchiseptica. AB - Wild-type Bordetella bronchiseptica and a bvg mutant strain were used for invasion and survival experiments in human Caco-2 and A549 epithelial cells. Both bacterial strains were able to enter and persist within the host cells for at least a week. A significant proportion of the bacteria from both B. bronchiseptica strains but not from Bordetella pertussis were found free in the cytoplasm, suggesting different invasion and survival strategies of the two species in epithelial cells. PMID- 8005691 TI - Immunological variants of the aerobactin-cloacin DF13 outer membrane protein receptor IutA among enteric bacteria. AB - Mouse monoclonal antibodies (MAbs) were generated against a 76-kDa IutA receptor of pathogenic avian Escherichia coli 15972. Six of the eight IutA-specific MAbs isolated (AB1 to AB6) were shown to be directed toward membrane-exposed conformational epitopes, although they did not interfere with the uptake of ferric aerobactin and cloacin DF13 as assessed by competition experiments with purified ligands. The two remaining IutA MAbs (AB9 and AB10) recognized linear epitopes buried in the IutA molecule. The panel of IutA MAbs was used to characterize IutA variants occurring in strains of E. coli, Klebsiella pneumoniae, Enterobacter spp., and Shigella spp., resulting in the identification of four immunological groups of IutAs. MAb AB9 defined an epitope conserved in all IutA variants. In addition, the panel of IutA MAbs served to identify the presence of IutA in wild-type bacteria grown in the presence of diphenylamine to reduce the expression of O-specific polysaccharide. PMID- 8005692 TI - Effect of Lewis blood group antigen expression on bacterial adherence to COS-1 cells. AB - Epithelial cells from secretor individuals demonstrate decreased bacterial adherence compared with cells from nonsecretors. Lewis blood group antigen expression is one component of the secretor/nonsecretor phenotype and several epidemiologic studies have suggested a link between Lewis blood group antigen phenotype and susceptibility to urinary tract infections. In this study, we examined the possibility that the expression of the difucosylated Lewis blood group determinants, Leb and Ley (associated with the secretor phenotype), made cells less susceptible to Escherichia coli adherence by masking receptors for pili. COS-1 cells, which do not produce Lewis (Lea, Leb, Le(x), and Ley) blood group antigens, were used as target cells for bacterial adherence. The surface blood group antigen expression pattern of the cells was then modified by cotransfection with plasmids containing DNA inserts encoding alpha (1,2) fucosyltransferase and alpha (1,3)- and alpha (1,4)-fucosyltransferases, resulting in the expression of Leb and Ley. E. coli HB101 expressing various adhesins (type 1, PapJ96, PapIA2, PapAD110, Prs, and S) from recombinant plasmids bound equally well to untransfected cells and transfected cells expressing Lea and Le(x) (nonsecretor phenotype) and Leb and Ley (secretor phenotype) antigens. We conclude that the presence of Leb and Ley antigens on cells from secretors does not alone mask receptors for E. coli pili or hinder bacterial adherence. PMID- 8005693 TI - Early gamma interferon mRNA expression is associated with resistance of mice against Yersinia enterocolitica. AB - T cells in cooperation with macrophages play an important role in resolution of primary Yersinia enterocolitica infection in mice. Previous work from this laboratory demonstrated that gamma interferon (IFN-gamma) and tumor necrosis factor alpha (TNF-alpha) are essential mediators of these processes. In an attempt to elucidate early mechanisms of resistance, we investigated cytokine mRNA production, including that for interleukin-1 beta (IL-1 beta), IL-2, IL-4, IL-6, IL-10, TNF-alpha, and IFN-gamma, after primary as well as secondary Y. enterocolitica infection in Yersinia-susceptible BALB/c mice and Yersinia resistant C57BL/6 mice. In both strains of mice, proinflammatory cytokines such as IL-1 beta, IL-6, and TNF-alpha were expressed rapidly and to comparable degrees, while IFN-gamma expression was enhanced two- to eightfold in C57BL/6 mice, as revealed by semiquantitative reverse transcription PCR. Similar results were found in both mouse strains after secondary Y. enterocolitica infection. IL 2 mRNA was detected only during secondary infection and disappeared rapidly in BALB/c mice. IL-4 mRNA expression was detectable in C57BL/6 but not BALB/c mice. The levels of cytokine mRNA expression correlated closely with the number of injected bacteria. The findings reported here support the hypothesis that early and enhanced production of IFN-gamma may be associated with a state of heightened resistance against Y. enterocolitica infection. PMID- 8005694 TI - Degradation of endogenous plasma membrane fibronectin concomitant with Treponema denticola 35405 adhesion to gingival fibroblasts. AB - Treponema denticola adhesion and degradation of fibronectin (Fn) on human gingival fibroblasts (HGF) were studied by immunofluorescence and enzyme-linked immunosorbent assays. The number of adherent bacteria increased and the amount of immunoreactive Fn decreased as a function of increasing T. denticola concentration. The distribution of cell-bound Fn was punctate in micrographs. Anti-human Fn impaired bacterial adhesion to HGF. Phenylmethylsulfonyl fluoride inhibited Fn degradation but not adhesion. Sonicated extracts and diluted spent growth medium degraded HGF Fn but, unlike intact T. denticola cells, they hardly stimulated F-actin rearrangements. PMID- 8005695 TI - The eaeB gene of enteropathogenic Escherichia coli is necessary for signal transduction in epithelial cells. AB - An enteropathogenic Escherichia coli mutant carrying an internal deletion in the eaeB gene (UMD864) was unable to activate epithelial cell signals, including tyrosine phosphorylation, cytoskeletal rearrangements, and the release of inositol phosphates, indicating that the eaeB locus encodes a product that is involved in stimulating signals in epithelial cells. PMID- 8005696 TI - Identification of a hemolytic activity elaborated by Haemophilus ducreyi. AB - Haemophilus ducreyi is the causative agent of the sexually transmitted disease chancroid. We have identified a hemolytic activity expressed by H. ducreyi. This activity is most readily detected when horse erythrocytes are used as a target; however, low levels of activity can be detected with sheep, human, or rabbit erythrocyte targets. The activity is heat labile and protease sensitive. PMID- 8005697 TI - The ethnic elderly in Metro Toronto Hospitals, nursing homes, and homes for the aged: communication and health care. AB - The ethnic elderly in Canada have remained a somewhat isolated group of seniors who become known when they enter our health care system as "aliens in their own country." They face the double jeopardy of not only declining sensibilities and increasing disabilities that frequently accompany old age but also the psycho social deprivation of being unable to communicate with caregivers in their institutional health care settings. Communication may be critical to effective, efficient, and equitable health care service delivery for ethnic elderly individuals. This study attempts to develop a database on the ethnic elderly persons, examine the extent of communication problems they face in hospitals, nursing homes, and homes for the aged in Metro Toronto, and report on the institutional responses to the situation. Nursing unit supervisors who completed the questionnaires (N = 77) reported that communication was essential to the health care needs of the ethnic elderly individuals. A majority of health care institutions had developed some form of interpreter services albeit frequently informal, unprofessional, and ad hoc. Without interpreter services problems developed that in some cases were seen as critical to the health care of ethnic elderly individuals. Even with interpreter services available, problems developed, suggesting that the services provided were not effective in some cases. It is suggested that further study be conducted to examine the relative effectiveness of formal, professional, and informal interpreter services. Few institutions had workshops or training to help staff understand ethnic variations on the perceptions of illness and health. PMID- 8005698 TI - Filial responsibility and informal support among family caregivers of the elderly in Jerusalem: a path analysis. AB - Informal family caregivers from a sample of 110 hospitalized elderly Jewish Jerusalemites were queried regarding their perceptions of filial responsibility and the supports they provide their parent(s). A path model was examined in which the outcome variable was a measure of the caregivers' expectations of future support. Background variables considered included sociodemographic variables and religiosity of the caregivers, family problems, proximity to the dependent parent, ADL, and length of dependency of the elderly care recipient. The analysis found future expectations of support to be explained principally by perceptions of filial responsibility, that were in turn explained by religiosity of the caregiver. Current support provided was influenced by proximity to the care recipient, ADL, length of dependency, and perceptions of filial responsibility. The implications of these findings for promotion of informal care are discussed. PMID- 8005699 TI - Retirement as a psychosocial transition: process of adaptation to change. AB - This study seeks to verify if the work-to-retirement process meets the requirements inherent to the Psychosocial Transitions Model. Quantitative and qualitative evaluations are used to verify if pre-, intra-, and post-retirement periods are different from one another when the individual's internal organization is examined. The experimental group (n = 17, age = 65) takes IPAT, LSI-A, and clinical interviews evaluations at pre-, intra-, and post-retirement measurement times. The control group (n = 22, age = 65), used to verify the test retest effect, takes these evaluations only at the post-retirement session. Variance analysis (ANOVA) show, at a quantitative level that the retirement transition triggers observable changes in anxiety levels. A posteriori analysis (HELMERT) shows that these operate significantly between the pre- and intra retirement times. The content analysis of interviews shows, at a qualitative level, observable changes in pre-post-retirement preoccupations. These include death thoughts. PMID- 8005700 TI - Changes in track and field performance with chronological aging. AB - Use of existing records to study performance decline with age has been recommended by several writers. This investigation attempts to identify one running, jumping, and throwing event whose performance was most affected by age. Results indicated that the 400 meter run and the long jump events were most affected by advancing age among both male and female master athletes whereas in the area of throws, the event most affected was the javelin for men and the discus for women. PMID- 8005701 TI - The effects of health, environmental, and socio-psychological variables on fear of crime and its consequences among urban black elderly individuals. AB - Despite extensive research on fear of crime among elder members of the population, little attention has been paid to the fear of crime among Black urban elderly individuals. Using a sample of 372 low income urban Black persons aged sixty-two and over the causes and consequences of such fear were investigated. Fear of crime reduces subjective well-being of these older adults and limits their mobility. Age, gender, education, marital status, loneliness, self-reported health status, previous victimization experience, media exposure, trust of neighbors, length of residence, and type of housing were tested to identify significant predictors of fear of crime. Some of these variables had a diverse impact on fear of crime at home versus outside of the home. For example, while gender was the strongest predictor of fear of crime outside the home, it was not significantly associated with fear inside the home. Surprisingly, self-reported health status was not related to fear of crime among this sample of urban Black elderly individuals. PMID- 8005702 TI - The influence of pentoxifylline on motility and viability of spermatozoa from normozoospermic semen samples. AB - In order to evaluate the effects of pentoxifylline on sperm motility and longevity, a controlled in-vitro study was conducted on normozoospermic donor semen samples using the Cellsoft automated system for sperm motility analysis. After incubation and selection, pentoxifylline was found to improve the recovery of spermatozoa and to increase their velocity. In the subgroup of progressively motile spermatozoa, curvilinear velocity was also enhanced. It is concluded that pentoxifylline has an effect on the vigour, but not on the pattern, of sperm motion. Pentoxifylline did not improve the motility characteristics of senescent spermatozoa in normozoospermic sperm samples. Sperm survival, as shown by supra vital staining, and motility longevity both decreased with time after pentoxifylline treatment. PMID- 8005703 TI - Simultaneous measurement of sperm LDH, LDH-X, CPK activities and ATP content in normospermic and oligozoospermic men. AB - Total lactate dehydrogenase (LDH), LDH-X, creatine phosphokinase (CPK) activities and ATP content were measured in washed spermatozoa from 188 normospermic and 94 oligozoospermic men. These four biochemical parameters were significantly higher (p < 0.001) in spermatozoa from oligozoospermic men than in those from normospermic men and were related inversely to sperm concentration. In oligozoospermic men the activity of sperm LDH and LDH-X was related significantly to sperm CPK activity (r = 0.5486 and r = 0.4442, respectively), whereas this relationship was less evident in normospermic men (r = 0.4124 and r = 0.3844, respectively). Sperm ATP content was related weakly to sperm LDH, LDH-X and CPK activities both in oligozoospermic and normospermic men. After separation on a discontinuous (40% and 80%) Percoll gradient LDH, LDH-X, CPK activities and ATP content in 80% separated sperm fractions from 48 normospermic and 30 oligozoospermic men were found to be significantly lower than in the initial semen sample in both groups of subjects. The 80% separated sperm fractions from oligozoospermic and normospermic men did not differ in their LDH or LDH-X activities or ATP content, whereas sperm CPK activity was still significantly higher in oligozoospermic men. These data suggest that, of the four parameters studied, high levels of intracellular CPK activity are the most relevant biochemical feature of spermatozoa from oligozoospermic men. PMID- 8005704 TI - Adenosine triphosphate and motility characteristics of fresh and cryopreserved human spermatozoa. AB - The concentration of ATP and the motility of human spermatozoa was measured in fresh and cryopreserved cells from the same 15 ejaculates. No coherent picture of the relationship between motility and ATP concentration emerged in whole semen or in spermatozoa washed by repeated centrifugation and resuspension in Biggers Whitten and Whittingham medium. This may have been due to the presence of dead spermatozoa and contaminating cells. After preparation on a Percoll gradient, the ATP concentration in fresh and cryopreserved spermatozoa was the same (6 +/- 0.7 nmol/10(8) spermatozoa) but 85 +/- 2.5% of the fresh spermatozoa were progressively motile with an average path velocity of 55 +/- 3.5 microns/s compared to corresponding values of 33 +/- 5.3% and 44 +/- 3.4 microns/s in frozen/thawed spermatozoa. This suggests that the poor motility of cryopreserved spermatozoa does not result from deficient ATP production. No relationship was found between ATP concentration and the ability of motile spermatozoa in the ejaculate to survive freezing. PMID- 8005705 TI - Seminal plasma lead, cadmium and zinc in relation to tobacco consumption. AB - The total quantity of zinc in the ejaculates of smokers was significantly lower than in non-smokers. This was not related to a significant increase in the quantities of seminal cadmium or lead, or to a decrease in sperm quality in the smoking group. It appears that tobacco consumption may have to exceed 20 cigarettes/day before a noticeable increase in seminal cadmium can be recorded. It is suggested that this reduction in zinc secretion may jeopardize the content of chromatin zinc, and thereby the stability of the sperm chromatin. This may then contribute to reproductive failure or have consequences for fetal development. PMID- 8005706 TI - Objective assessment of spermatogenesis in men with functional and anatomic obstruction of the genital tract. AB - Experimental rodent models simulating the condition of neurogenic infertility have drawn attention to the role of potential epididymal dysfunction as an underlying cause. This functional obstruction of the genital tract is comparable to the outcome of genital tract obstruction after vasectomy, and may explain the common finding of asthenospermia in both groups following either stimulated semen recovery or vasovasostomy, respectively. Since spermatogenic dysfunction has been reported in spinal cord injury, the relative roles of defective sperm production and sperm transport remain to be determined in men with neurogenic infertility. The objective of this study was to compare the levels of spermatogenesis in groups of vasectomized men and those with spinal cord injury, using objective measurement criteria for spermatogenesis. Groups of 10 spinal cord-injured and six vasectomized men matched for age and duration of disease, underwent incisional testicular biopsy. The specimens were divided equally for parallel quantitation of spermatogenesis by both quantitative cytometry and DNA flow cytometric analysis. Quantitative parameters showed similar values for both groups with reference to mean tubular wall thickness, mean tubular concentration of spermatids and Sertoli cells, as well as the mean spermatid: Sertoli cell ratio per tubule. Additionally, similar percentages of 1N, 2N and 4N cells, were found in both groups. Based on these preliminary findings this study provides a clinical correlation supporting the experimental observation that both anatomical and functional obstruction of the male genital tract exert a similar although minor spermatogenic insult, and that in both the putative cause for neurogenic infertility is more likely to be at the post-testicular level. PMID- 8005707 TI - Affinity sites for N-acetyl-beta-D-glucosaminidase on the surface of rat epididymal spermatozoa. AB - The binding of N-acetyl-beta-D-glucosaminidase from rat epididymal fluid to the surface of spermatozoa from the cauda epididymis was measured in the presence of sugars, its phosphorylated derivatives, or after treatment of the cells or the enzyme with agents that alter the integrity of proteins or carbohydrates. The binding was saturable, with a Kd in the nanomolar range, was inhibited with phosphorylated derivates of fructose, and did not depend on Ca2+, showing that it is different from the mannose 6-P-recognizing system existing in other tissues for this and other acid hydrolases. Treatment of the cells with sodium periodate or trypsin inhibited the binding, showing that a glycoprotein of the plasmalemma is involved in the affinity site. Fructose or phosphorylated derivates were not detected in the proteins of the epididymal fluid with HPLC. However, with the method used, the presence of these compounds cannot be ruled out, if among the proteins of the fluid there are only a small number of acid hydrolases containing this sugar. PMID- 8005709 TI - Urine as an alternative to urethral swabs for the diagnosis of Chlamydia trachomatis in infertile males. AB - Swabbing the urethrae of men has been the traditional approach for collecting specimens for detection of Chlamydia trachomatis. Recently, however, urine testing using enzyme immunoassay has yielded promising results. A total of 105 patients attending the Andrology Clinic at Ga Rankuwa Hospital, Medunsa were included in the study. These patients were asymptomatic and had no urethral discharge. Three endo-urethral swabs and first-catch urine were collected from each patient. The urethral swabs were used for enzyme immunoassay (EIA) (IDEIA III), tissue culture and direct immunofluorescent antibody (DFA) test (IMAGEN) to detect C. trachomatis. In addition about 15-30 ml of first-catch urine, or urine collected at least 2h after the previous micturition, was collected for each patient for EIA testing. Fifteen (14.3%) of 105 patients were positive on urethral swab EIA, in comparison with the DFA test in which 14 (13.3%) were positive. Eight (7.8%) were positive in tissue culture. Urine EIA was positive in 17 (16.2%) patients, of whom five (4.8%) were positive in urine EIA only. All EIA positive urines were confirmed by DFA. We recommend that first-catch urine or urine collected at least 2h after the previous micturition in infertile males may be considered a suitable alternative to urethral swab for chlamydial diagnosis because it is noninvasive and nontraumatic. PMID- 8005708 TI - Effects of retinol on glycoprotein synthesis by Sertoli cells in culture: dolichyl phosphomannose synthase activation. AB - Sertoli cells were isolated from Wistar rats aged 19 days and cultured for 48 h. The addition of retinol (10 microM) to the culture medium significantly stimulated the incorporation of [2-3H]mannose into lipid-linked oligosaccharide and into cellular and secreted glycoproteins. Incorporation of [U-14C] leucine into proteins and of [5, 6-3H] uridine into RNA was unaffected by retinol treatment. Incubation of microsomal fractions of retinol-treated cells showed an increase in mannose incorporation into dolichyl phosphomannose, into dolichyl pyrophosphoryl oligosaccharide and into proteins. Chromatographic analysis of the fraction soluble in chloroform/methanol (2:1 v/v) did not show the presence of retinyl phosphomannose either in control or in retinol-treated cells. When the formation of dolichyl phosphomannose was studied in microsomes isolated from control cells and from cells treated with 10 microM retinol for 48 h in the presence of exogenous dolichyl phosphate, the results showed that the retinol effect was due to stimulation of dolichyl phosphomannose synthase. PMID- 8005710 TI - Neural network approach in multichannel auditory event-related potential analysis. AB - Even though there are presently no clearly defined criteria for the assessment of P300 event-related potential (ERP) abnormality, it is strongly indicated through statistical analysis that such criteria exist for classifying control subjects and patients with diseases resulting in neuropsychological impairment such as multiple sclerosis (MS). We have demonstrated the feasibility of artificial neural network (ANN) methods in classifying ERP waveforms measured at a single channel (Cz) from control subjects and MS patients. In this paper, we report the results of multichannel ERP analysis and a modified network analysis methodology to enhance automation of the classification rule extraction process. The proposed methodology significantly reduces the work of statistical analysis. It also helps to standardize the criteria of P300 ERP assessment and facilitate the computer aided analysis on neuropsychological functions. PMID- 8005711 TI - A BASIC program for the peak-to-valley estimation of respiratory sinus arrhythmia. AB - A computer program for the automatic scoring of respiratory sinus arrhythmia (RSA) is described. The program uses the 'peak-to-valley' quantification of RSA. Data was collected on 20 subjects to determine the inter-rater reliability and efficiency of the program. Highly reliable estimates of RSA were found. Advantages and limitations of the program are discussed. PMID- 8005712 TI - Improved equipment for abdominal fetal electrocardiogram recording: description and clinical evaluation. AB - Reliable computer-based equipment for transabdominal or indirect recording of fetal electrocardiogram (FECG) is described. The proposed equipment allows a real time displaying of the signals (fetal + maternal ECG) without averaging procedures and it does not require the employment of a shielded room; moreover, it is user-friendly to medical personnel. An elementary form of semi-automatic computation of the fetal heart rate (FHR) was also implemented. The equipment simultaneously acquires three signals from seven electrodes, six placed on the maternal abdomen following the three space axes, and one placed on the left leg as a indifferent electrode. The signals are magnified and analogically filtered before undergoing digital finite impulse response (FIR) filter. Then the signals are displayed on the screen of a personal computer (PC). The PC also provides the possibility of storing the acquired signals for further analysis of elaborations. The quality of the recordings allows the analysis of both the rapid and slow electrical phenomena of the fetal heart, and it is not significantly influenced by the occurrence at the same time of uterine contractions. The performance of this method was assessed in 140 pregnant women with gestation periods of 29-42 weeks. In 131 cases (93.6%) the fetal QRS complex was detected and the FHR was obtained. A reliable evaluation of P and QRS waves and of ST interval, in spite of the interference of the maternal complexes, was possible in 102 cases (72.8%). PMID- 8005713 TI - Data compression by linear prediction for storage and transmission of EEG signals. AB - The EEG time series has been subjected to various formalisms of analysis to extract meaningful information regarding the underlying neural events. In this paper the linear prediction (LP) method has been used for analysis and presentation of spectral array data for the better visualisation of background EEG activity. It has also been used for signal generation, efficient data storage and transmission of EEG. The LP method is compared with the standard Fourier method of compressed spectral array (CSA) of the multichannel EEG data. The autocorrelation autoregressive (AR) technique is used for obtaining the LP coefficients with a model order of 15. While the Fourier method reduces the data only by half, the LP method just requires the storage of signal variance and LP coefficients. The signal generated using white Gaussian noise as the input to the LP filter has a high correlation coefficient of 0.97 with that of original signal, thus making LP as a useful tool for storage and transmission of EEG. The biological significance of Fourier method and the LP method in respect to the microstructure of neuronal events in the generation of EEG is discussed. PMID- 8005714 TI - Constructing a dental electronic information resource (DEIR). AB - This paper discusses the construction of a dental electronic information resource (DEIR). Development is based on the Internet gopher client/server model. Information is organized in a series of hierarchical menus. A DEIR can be browsed by traversing the menu hierarchy or by performing keyword searches. Searches can result in a menu of found items from across the Internet. Initially, contents of the DEIR will be text files. Electronic copy will be given to an editorial board that will review submissions for conformity to publication standards. A current estimate for electronic storage costs of a DEIR is $1.25/Mb per year. There will be additional costs associated with any purchases of data (e.g. Current Contents), production of data (e.g. development time), and editorial and managerial activities. The DEIR will be accessible from any computer or terminal that can connect to the Internet. Primary user groups will be faculty, staff, and students of dental schools. However, access to the DEIR will be free, and an extensive user community will be encouraged, including practicing dentists, dental associations, public health agencies, and dental insurance companies. PMID- 8005715 TI - House calls: a support group for individuals with AIDS in a community residential setting. AB - The author describes a support group led by two psychiatrists for individuals with AIDS set in the participants' residence, the AIDS Community Residence Association (ACRA) House. Similar to other AIDS groups described in the literature, the residents spoke of existential fears such as losing their physical beauty or intellect. In contrast to the intimate and familial atmosphere of many other AIDS groups, the members' strong sense of invasion by the facilitators and their ongoing ambivalence were striking. This reaction toward the group and the co-leaders appeared to be metaphorically related to the "invasion" of illness and health care workers into their lives. As members better tolerated and expressed these thoughts and feelings, a greater intimacy and sense of "family" emerged. PMID- 8005716 TI - A suicide in group: a case of functional realignment. AB - This article explores the consequences of a therapy group member's suicide on a group's interaction and coping style. The exploration takes an ethnographic approach, which emphasizes a deep description of the circumstances surrounding the group member's death, the meaning of that action for the members, including the therapists, and the group coming to terms with the crisis. PMID- 8005717 TI - Stages of group psychotherapy supervision: a model for supervising beginning trainees of dynamic group therapy. AB - This article presents a model for supervising beginning therapists of dynamic group psychotherapy. It is geared to their experience with the challenging patients most often seen in training clinics. The model presupposes no particular metapsychology but, to meet trainees' needs, advocates a hierarchically organized set of operational goals. The supervision is conceptualized as ideally occurring in three sequential stages: (a) The "Technical" phase conveys the fundamentals of technique, the "craft." (b) The "Enrichment" stage emphasizes appreciation of group phenomena, including formal group dynamic theory. (c) The final phase highlights the more "Personal" side of becoming a skilled group psychotherapist, including countertransferential issues and the termination process. The model, not intended to be applied in a Procrustean manner, also serves, nevertheless, as a description of how a satisfactory supervision for beginners generally proceeds. PMID- 8005718 TI - Intensive analysis of therapeutic factors and outcome in long-term inpatient groups. AB - Two long-term analytic inpatient groups comprised of severely disturbed neurotic and personality disordered patients were intensively investigated through process ratings and therapist and patient reports with regard to five therapeutic factors: cohesiveness, self-disclosure, feedback, interpersonal learning-output, and family re-enactment. The process variables were correlated with outcome assessments at 12 and 18 months following treatment. The study applied a single case (group) approach with replication to cross-validate the findings from one group to the next. Results demonstrated that all five therapeutic factors were meaningfully associated with clinical improvement. Although different treatment groups may generate unique psychological climates for producing change, the findings suggest that group cohesiveness is an important ingredient for effective group process to occur. The multimethod, multiperspective nature of this study lends considerable credence to the findings, despite the small sample size. PMID- 8005719 TI - The uses of an observation team with a parent support group. AB - This brief report examines the uses of an Observation Team with a Parent Support Group. In particular, attention is placed on the idea of the Observation Team acting as a Reflecting Team in the final session of the group's life. Using the Observation Team in this manner has evolved from an amalgamation of ideas from family therapy and group therapy theory. PMID- 8005720 TI - The structure of Yalom's Curative Factors Scale. AB - Factor analysis was used to evaluate the short form of Yalom's Curative Factors Scale with data from 372 participants in the 1986 American Group Psychotherapy Association Institute Groups. With the data randomly assigned to three subgroups, results showed 10 scale items loading on three factors across all three subgroups. When the data was organized into two self-selected subgroups corresponding to the two Institute group categories, factor analyses showed the first factor to be consistent with the previous analyses, but other factors showed differences interpreted to be characteristic of the two groups' modalities. The study suggests a framework for understanding the concept of therapeutic factors and how they work together. PMID- 8005721 TI - Exercise limitations in patients with pulmonary diseases. AB - An adequate analysis of the pathophysiology of the disease and of its ensuing type and degree of limitations is essential for evaluating the abilities for physical performance in patients with pulmonary diseases. Maximal exercise testing is an indispensable diagnostic tool in this respect. In light of moderate obstructive disease (FEV1 > approximately 60% pred), the exercise limitation comes from the cardio-circulatory system and/or peripheral muscle function. A rehabilitation program for these patients can be based on endurance training at high heart rate levels. Patients with a ventilatory limitation (FEV1 < 40%-60% pred.) show a failure of the respiratory pump, resulting in hypercapnia during exercise. Rehabilitation treatment will contain ergonomics, exercises for mobility and agility, breathing exercises with low-frequency breathing, relaxation exercises, and inspiratory muscle training. An oxygen-uptake limitation can be found in patients with a diffusion problem, severe ventilation perfusion mismatch, or a reduced contact time between blood and alveolar gas. Such problems can often be seen in emphysema, and express themselves as isolated hypoxaemia during exercise. These patients benefit from a program consisting of ergonomics, exercises for mobilising the thoracic wall, low-frequency breathing, and exercising with additional oxygen. Many patients with chronic obstructive pulmonary disease (COPD) are limited for psychosocial reasons. The dyspnea is a negatively rewarding side effect of exercise in these patients. They tend to avoid all exertion, and thus get into a vicious circle of inactivity, low fitness, and unpleasant sensations during exercise. The inactivity often is also induced by the patient's family, since a 'patient-role' requires a quiet lifestyle. PMID- 8005722 TI - Human power output and muscle fatigue. AB - In human locomotion the ability to generate and sustain power output is of fundamental importance. This review examines the implications for power output of having variability in the metabolic and contractile properties within the population of muscle fibres which comprise the major locomotory muscles. Reference is made to studies using an isokinetic cycle ergometer by which the global power/velocity relationship for the leg extensor muscles can be determined. The data from these studies are examined in the light of the force velocity characteristics of human type I and type II muscle fibres. The 'plasticity' of fibre properties is discussed with reference to the 'acute' changes elicited by exercise induced fatigue and changes in muscle temperature and 'chronic' changes occurring following intensive training and ageing. PMID- 8005723 TI - The maintenance of fluid balance during exercise. AB - Fluid supplementation is necessary for exercise in which fluid losses must be offset by intake to avoid the negative effects of hypohydration on health and performance. Several aspects of gastrointestinal function have been studied to gain information concerning the assimilation of ingested fluids to maintain fluid balance during exercise. Research results with regards to gastric emptying and secretion, intestinal absorption and secretion, and aspects of fluid retention, including urine production and plasma volume changes, can be utilised to formulate an appropriate fluid supplementation regimen. Increasing the volume of ingestate and decreasing the carbohydrate concentration promote gastric emptying of fluids. By maintaining a low osmolality secretion is reduced, thus leading to a greater rate of net fluid absorption. Adding sodium and carbohydrate (up to approximately 7%) increases the net intestinal absorption rate. Increasing carbohydrate concentration above this level begins to have a deleterious effect on intestinal absorption of fluid. Sodium also promotes retention of ingested fluids and leads to an increased plasma volume response during rehydration. The primary goal of supplementation should be considered, fluid vs carbohydrate provision, and the beverage composition altered accordingly. Beverage composition to maximise fluid provision will not maximise carbohydrate availability. PMID- 8005724 TI - Circulatory responses during arm exercise in individuals with paraplegia. AB - Since there is an increasing demand for sport and exercise in daily life activities and rehabilitation of persons with a spinal cord injury, it is important to gain insight into the circulatory responses during exercise in these individuals. Recently, some studies have addressed this issue. The purpose of this paper, therefore, is to review briefly the current knowledge on circulatory responses during submaximal and maximal arm exercise in individuals with paraplegia and the differences in these responses compared to able-bodied persons. Emphasis is placed on the redistribution of blood during arm exercise in persons with paraplegia. Special attention is focused on the so-called "venous blood pooling" below the spinal cord lesion and the available techniques to support the redistribution. In addition, the effect of heat stress on the circulatory adjustment during exercise and the influence the level of the lesion has on the circulatory responses are outlined. Topics for future research are suggested throughout the paper. PMID- 8005725 TI - Exercise-induced muscle damage. AB - Muscular overuse is associated with structural damage of the contractile elements and reflected in delayed onset muscle soreness (DOMS). Mechanical stress is supposed to be the major contributing factor for inducing muscle damage. The initial damage is followed by an inflammatory response and eventually by regeneration. Calcium is assumed to play an important role in triggering the inflammatory changes. Biopsy data in man indicate that the inflammatory changes in humans do not parallel the soreness ratings, leaving the delayed onset of muscle soreness unexplained. It is a well known phenomenon that one bout of eccentric exercise has a long lasting protective effect against damage induced by a second bout of exercise. Experimental evidence suggests that this adaptation can partly be attributed to an increase in connective tissue. Plasma CK activity has widely been used as a marker for the amount of muscle damage. It has been shown that gender differences in exercise-induced CK release are caused by sex hormones dependent differences in sarcolemmal permeability. Plasma CK activity does not necessarily reflect the amount of structural damage. PMID- 8005726 TI - Exercise, stimulation and type transformation of skeletal muscle. AB - Although chronic electrical stimulation of muscles over a period of weeks produces a profound slowing of their contractile characteristics, such changes do not form part of the response to endurance training. The reasons for this apparent anomaly are contained in the organization of the final common pathway of the motor system and the orderly way in which it is recruited. There is also a need to introduce the notion of thresholds for the transitions from one fibre type to another. The conceptual framework that emerges from these ideas enables us to take a scientific approach to the problems posed by the clinical applications of electrical stimulation. PMID- 8005727 TI - Functional neuromuscular stimulation. Exercise conditioning of spinal cord injured patients. AB - The results of numerous research studies indicate that functional neuromuscular stimulation (FNS)-induced exercise training of the paralyzed lower-limbs of spinal cord injured (SCI) patients can result in several important health and fitness benefits that cannot be achieved solely through conventional arm exercise modes. These benefits include peripheral adaptations where muscle strength, endurance, girth and appearance can be improved, as well as central circulatory adaptations which enhance aerobic (cardiopulmonary) capacity. There is also evidence that secondary medical complications related to sedentary lifestyle and inadequate circulation of blood can be prevented or alleviated with FNS exercise. The purpose of this paper is to present various FNS exercise modes including knee extension weight training, leg cycling and a hybrid exercise (voluntary-arm cranking and FNS-leg cycling), and to provide physiologic response patterns that are elicited. PMID- 8005728 TI - Applied physiology of strength and power in old age. AB - The loss of strength and power in old age has important implications for health. Even with healthy elderly people, cross-sectional comparisons imply a loss of strength at some 1.5% per year and of power at some 3.5% per year (averaged across the age range 65 to 84). On the other hand, healthy, very elderly people are at least as responsive to strength-training as younger adults. It is important to establish whether elderly people derive functional benefit from training-induced improvements in strength and whether laboratory measurements of strength and power might be used to identify those elderly people most at risk of losing important, everyday functional abilities. PMID- 8005729 TI - High efficiency of type I muscle fibers improves performance. AB - We have recently demonstrated that people with a high percentage of Type I muscle fibers display a relatively high muscular efficiency when cycling. These individuals generate a relatively high muscular power output at a given steady state level of oxygen consumption and caloric expenditure. The purpose of this study was to directly determine the extent to which differences in muscle fiber composition and efficiency influence endurance performance in competitive cyclists. The percentage of Type I and II muscle fibers was determined from several biopsies from the vastus lateralis which were histochemically stained for ATPase activity. During a laboratory performance test, 14 endurance trained cyclists (mean +/- SE; VO2max, 5.2 +/- 0.11/min; body weight, 74 +/- 1 kg) cycled an ergometer for 1 h at the highest work rate they could tolerate. VO2 and RER were simultaneously measured using open circuit spirometry for calculating caloric expenditure. Subjects were divided into two groups of seven according to their muscle fiber type composition: High % Type I Group (> 56% Type I fibers); Normal % Type I Group (38-55% Type I fibers). Each subject from High % Type I Group was paired with a subject from the Normal % Type I Group according to their similarity in VO2max, blood lactate threshold and average VO2 maintained during the 1 h performance test. Both groups averaged 4.5 +/- 0.11/min during the 1 h performance test (i.e., 86-88% VO2max).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8005730 TI - Residual lung volume and ventilatory muscle strength changes following maximal and submaximal exercise. AB - In order to evaluate a mechanism which may be responsible for the often observed acute increase in residual lung volume (RV) following exercise, 12 non-smoking males (20-30 yrs) performed two bouts of exercise on separate days; one to maximal heart rate (HRmax) and one to 85% of HRmax for 20 min. Prior to exercise and at 5, 15, 30, 60 and 120 min post-exercise, the following parameters were measured: RV, forced vital capacity (FVC), forced expiratory volume (FEV1.0), forced expiratory flow (FEF75-85), maximal expiratory pressure (PEmax), and maximal inspiratory pressure (PImax). Significant (p < 0.05) increases occurred in RV at 5, 15 and 30 min following maximal exercise and at 5 and 30 min after submaximal exercise. Changes in RV between the two exercise bouts were generally greater (p < 0.05) for maximal exercise. Accompanying the increases in RV were significant (p < 0.05) decreases in PEmax and decreases in FVC, while FEV1.0 and FEF75-85 remained generally unchanged or were slightly elevated. The data suggest that decreases in expiratory muscle strength due to fatigue may in part be responsible for increases in RV. PMID- 8005731 TI - Sex steroid biosynthesis enzymes in ovarian sex-cord stromal tumors. AB - Previous studies on neoplastic and hyperplastic ovarian lesions using paraffin embedded material have demonstrated immunolocalization of sex steroid biosynthetic enzymes (SSBEs): P-450 side chain cleavage (P-450 SCC), which converts cholesterol to pregnenolone; 3 beta-hydroxysteroid dehydrogenase (3 beta HSD), which converts pregnenolone to progesterone; P-450 17 alpha-hydroxylase and lyase (P-450 17A), which convert progesterone to 17 alpha-hydroxyprogesterone and 4-androstene-3,17-dione; and P-450 aromatase (P-450 AR), which converts 4 androstene-3,17-dione to estradiol. To investigate the utility of immunohistochemical staining for SSBEs, we studied a series of 45 sex cord stromal tumors of the ovary. P-450 SCC was present in 9 of 11 Sertoli-stromal cell tumors, 3 of 12 granulosa cell tumors, 2 of 7 thecomas, and 1 of 1 stromal luteomas; 3 beta-HSD was present in 5 of 11 Sertoli-stromal cell tumors, 2 of 12 granulosa cell tumors, 2 of 7 thecomas, and 1 of 1 stromal luteoma; P-450 17A was present in 5 of 11 Sertoli-stromal cell tumors, 2 of 12 granulosa cell tumors, 2 of 6 thecomas, and 1 of 1 stromal luteomas; P-450 AR was present in 6 of 11 Sertoli-stromal cell tumors, 2 of 12 granulosa cell tumors, none of 7 thecomas, and 1 of 1 stromal luteoma. SSBEs were not present in 12 fibromas, one sclerosing stromal tumor, and one myxoma. Five of 45 patients with sex cord-stromal tumors showed androgenic effects; 4 of 11 patients with Sertoli-stromal cell tumors and the patient with a stromal luteoma. These five sex cord-stromal tumors contained P-450 SCC, and three of four of the Sertoli-stromal cell tumors contained 3 beta HSD, P-450 17A, and P-450 AR. Concurrent endometrial histology was available in 25 of 45 sex cord-stromal tumor patients. None of the five sex cord-stromal tumors arising in patients with endometria that showed hyperplasia or adenocarcinoma showed immunoreactivity for SSBEs. Eight patients' endometria were unremarkable, but their sex cord-stromal tumor contained SSBEs. SSBEs were present in areas showing Leydig cell, Sertoli cell, or steroid cell differentiation or luteinized areas; however, the results did not significantly add to the histologic classification of sex-cord stromal tumors. Androgenic hormonal effects could always be explained by synthesis of hormones by SSBEs present in the patient's sex cord-stromal tumor.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8005732 TI - Ovarian involvement by serous surface papillary carcinoma. AB - Serous surface papillary carcinoma (SSPC) is a multicentric peritoneal tumor that can spare or minimally involve the ovaries and has been reported to be more aggressive than the usual form of serous carcinoma of the ovary (SCO). From 360 serious ovarian carcinomas, we selected 87 cases with high histological grade, clinical stage III, residual disease after the first operation, similar chemotherapeutic regimens, and at least a 4-year follow-up period. Of these, 33 patients had SSPC in which the tumors were smaller than 10 mm (ovaries not enlarged), and 54 had SCO in which the tumors were larger than 5.0 cm. The 33 cases with SSPC were then subdivided according to tumor size: (a) 17 patients had SSPC characterized by tumors that were smaller than 5.0 mm in largest dimension and that involved only the ovarian surface or showed minimal superficial invasion of the ovarian cortex (maximum depth, 3 mm); (b) 16 patients had SSPC characterized by tumors that measured 5.1 to 10 mm and involved the ovarian surface, cortex, and/or medulla. The subdivision of the SSPC into small and large types was found to be of no clinical statistical significance; thus, the two groups were recombined as a single group. The difference in length of survival between SSPC and SCO at 24 months (39% versus 32%, respectively) and the median survival times (SSPC = 17 months and SCO = 18 months) were not statistically significant. However, the 48-month survival rate (SSPC = 28% and SCO = 9%), was statistically significant (p = 0.027).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8005733 TI - Immunocytochemical analysis of uterine papillary serous carcinomas for estrogen and progesterone receptors. AB - Uterine papillary serous carcinoma (UPSC), an aggressive histologic variant of endometrial cancer, is particularly resistant to cytotoxic chemotherapy. In reviewing a group of patients treated with cisplatin, doxorubicin, and cyclophosphamide, we were surprised to find that 90% of specimens tested by biochemical analysis were positive for estrogen receptor (ER), progesterone receptor (PR), or both. To further study receptor content and localization, we performed immunocytochemical analysis (ICA) on 29 archival UPSC specimens. In ER studies, three specimens were unevaluable because of inadequate internal controls; of the remaining 26, only two were ER positive, showing weak, focal staining. In PR studies, 18 samples had adequate controls, and all tumor specimens were receptor negative. Corresponding biochemical ER data were available for 11 cases, of which 10 were ER positive. ICA, however, showed all 10 to be negative. Biochemical PR data were available for seven samples: Six were positive. All six biochemically positive PR specimens were PR negative when analyzed by ICA. Biochemical assays for ER and PR may overestimate positivity as a result of contamination with normal tissue or the presence of receptor-positive typical endometrial adenocarcinoma in tumors of mixed histology. ICA may eliminate this problem, but it has technical limitations, especially when used for archival tissue analysis. Because urinary papillary serous carcinoma appears to be a receptor-negative tumor, further evaluation of hormonal therapy is not likely to be beneficial. PMID- 8005734 TI - Argyrophilic cells in cervical intraepithelial glandular neoplasia. AB - Argyrophilic cells occur rarely in the normal cervix but are found in a variety of invasive tumours arising in the cervix. We searched for argyrophilic cells by using Grimelius staining in 25 cases of high-grade intraepithelial glandular neoplasia of the cervix and identified them in seven cases. This study shows that argyrophilic cells are also often found in preinvasive glandular lesions of the cervix. PMID- 8005735 TI - Detection of human papillomavirus (HPV) DNA in cervical swabs by the polymerase chain reaction: an evaluation of the sensitivity of the method in patients with HPV 16-harboring cervical lesions. AB - The polymerase chain reaction (PCR) was used to detect human papillomavirus (HPV) type 16 DNA in cervical swabs from 37 patients with HPV 16-harboring cervical lesions (15 carcinomas and 22 cervical intraepithelial neoplasias). Primers amplifying a sequence of the human beta-globin genome were used for internal control together with the HPV 16-specific primers. The cell samples were prepared for PCR analysis by two different methods: either by phenol/chloroform extraction or by boiling in the presence of a chelating agent. HPV 16 DNA was found in 27 swabs. The detection rates were identical with both methods of preparation. Four of the 10 false-negative swabs contained too little DNA to permit amplification with the genomic primers. Excluding these insufficient samples, the detection rate was 82%. Reasons for false-negative results may include low cell numbers or failure to obtain cells representative of the underlying lesion. In conclusion, the PCR offers a satisfactory method of HPV detection in cervical swabs. Cell preparation can be restricted to simple boiling with a chelating agent. For optimal results, samples containing less than 2 x 10(4) cells should be discarded, and genomic primers should be used for internal control. PMID- 8005736 TI - Adenocarcinoma in situ of the endocervix: human papillomavirus determination by dot blot hybridization and polymerase chain reaction amplification. AB - The frequency of human papillomavirus (HPV) in series of endocervical adenocarcinoma in situ (AIS) ranges from 6 to 100%. Some of this variability can be attributed to small study numbers and such technical considerations as the sensitivity of the hybridization method employed. Consequently, the role of the HPV in AIS oncogenesis is unclear. The frequency and relative distribution of HPV DNA types 6, 11, 16, 18, 31, 33, and 35 in 37 cases of AIS were determined and correlated with clinical variables. All cases were first typed by dot blot hybridization (DBH), and those found to be HPV negative were subsequently typed by polymerase chain reaction amplification with DBH enhancement (PCR/DBH). The HPV DNA positivity rate was 27% by DBH alone and 52% by PCR/DBH amplification. Combining the results of both methods, the overall HPV positivity rate was 66%: HPV 18 in 15 cases (43%), HPV 16 in eight cases (23%). The HPV status did not correlate with any clinical variable. This study showed that the sensitivity of the hybridization method is principally accountable for the variable frequency of HPV in AIS. The identification of only high-risk oncogenic HPV types in two thirds of the cases suggests a significant role for the virus in AIS oncogenesis; HPV status, however, does not delineate a clinical profile. PMID- 8005737 TI - Mammary-like glands of the vulva and their disorders. AB - Supernumerary mammary glands derived from rudiments of the embryonic milk lines or mammary ridges in the vulva are considered a source of a series of unusual tumors resembling lesions of the breasts. This phenomenon was reevaluated in light of recent observations of mammary-like anogenital glands (MLG), which are a normal constituent of the vulva and appear to be closely related to eccrine glands. An analysis of the literature reveals that the concept of "milk lines" originated in a mixture of phylogenetic and ontogenetic theories at the beginning of this century and was not supported by observations in human embryos, which show that primordia of the mammary glands do not extend beyond the axillary pectoral area. The breasts and the vulva are so widely separated by time and space that the vulvar MLG can not be derived from the mammary ridges or milk lines. The profile of the MLG, which can also reveal some eccrine or apocrine features, makes these glands the most likely source of a series of lesions occurring in the anogenital region and comprising lactating glands, lactating adenoma, fibroadenoma, hidrocystoma, hidradenoma papilliferum, and most cases of extramammary Paget's disease and invasive adenocarcinoma. PMID- 8005738 TI - Synoptic reports in gynecologic pathology. PMID- 8005739 TI - Transitional cell carcinoma of the fallopian tube: a light and electron microscopic study. AB - Carcinomas other than adenocarcinomas are extremely rare in the fallopian tube. We report a case of a malignant neoplasm of the fallopian tube with histological features of transitional cell carcinoma that presumably arose from an extraluminal region of the tube. A 57-year-old postmenopausal woman with vaginal bleeding was found to have a left adnexal tumor. Exploratory laparotomy revealed a left tubal tumor with a metastatic nodule on the rectal surface. Histologically, the tumor surrounded the lumen of the left fallopian tube and was composed of cells with "coffee-bean"-like nuclei arranged in solid nests without keratinization. No abnormalities were found in the right tube, ovaries, or uterus. Electron microscopy revealed the tumor cells to have nuclei with deep nuclear indentations, cytoplasmic tonofilaments, and intercellular spaces with prominent interdigitations of the cell membrane. In addition, several tumor cells with protruding microvilli formed abortive lumina. These histological and ultrastructural features were consistent with the diagnosis of transitional cell carcinoma. PMID- 8005740 TI - Ovarian metastasis from thyroid carcinoma 12 years after partial thyroidectomy mimicking struma ovarii: report of a case. AB - A 29-year-old woman experienced abdominal swelling 12 years after undergoing partial thyroidectomy for follicular carcinoma of the thyroid with vascular invasion and 6 months after a right cerebral tumor that had caused hemiplegia had been excised. Laparotomy disclosed a solid and cystic right ovarian tumor, 17 cm in greatest dimension, and a 12-cm tumor of the right adrenal gland. Microscopic examination showed a malignant tumor of the thyroid follicular type with frequent mitotic figures; other teratomatous elements were absent. Because of the interval since the thyroid cancer, the diagnosis of a malignant struma ovarii was initially considered. The patient rapidly developed widespread metastatic disease and died, supporting the interpretation that the ovarian tumor was a metastasis from the thyroid neoplasm. This case illustrates that when other teratomatous elements are not identified, the diagnosis of malignant struma ovarii should be made only when the possibility of spread from a prior thyroid neoplasm, possibly one treated many years previously, has been excluded. PMID- 8005741 TI - Lymphoepithelioma-like carcinoma of the vagina: a case report with special reference to the immunophenotype of the tumor cells and tumor-infiltrating lymphoreticular cells. AB - Lymphoepithelial carcinoma (Schmincke's tumor) is a relatively common malignancy in the upper respiratory tract (nasopharynx), but it rarely occurs at other sites. We describe here the first case of a vaginal neoplasm that closely resembled lymphoepithelial carcinoma in its histological features and immunophenotype. The tumor was detected in an 81-year-old woman who presented with recurrent vaginal bleeding. On colposcopy, an ulcerated polypoid tumor mass was seen in the posterior wall of the middle portion of the vagina. Histologic examination revealed an undifferentiated spindle-cell carcinoma (KL1+, chromogranin A-, vimentin-) with abundant lymphocytes (mostly UCHL1+ T cells), plasma cells, and macrophages (CD68+) in and around the tumor cell nests. A minority of the tumor cells exhibited overexpression of p53 protein and a quarter of the tumor cells reacted with the antibody MIB1, that is, were in a proliferate state. The tumor cells did not react with the monoclonal antibody DAKO-EBV, which detects a latent membrane protein (LMP-1) encoded by the Epstein-Barr virus. The tumor underwent regression after radiotherapy. No signs of recurrence or dissemination of the carcinoma have been detected clinically during the 6 months since treatment. PMID- 8005742 TI - Evaluation and comparison of histopathologic grading systems of epithelial carcinoma of the uterine cervix: Gynecologic Oncology Group studies. AB - The subjects of this study are 445 patients with advanced cervical cancer treated by standardized radiation therapy. Upon entry into one of two Gynecologic Oncology Group (GOG) protocols, original pathologic diagnoses and histologic tumor descriptions for each patient were compared with separate evaluations made by a consensus opinion of two GOG pathologists. A review diagnosis using grade, cell type, and the Stendahl scoring system was then made by the first author (R.J.S.) without knowledge of the prior diagnoses. Of the original pathologists' diagnoses, 21% did not include grade or cell type. There was little agreement among the different pathologists as to the use of either specific grade or cell type. Histologic grade, irrespective of the pathologists making the diagnosis, had no correlation to prognosis. The Reagan and Wentz large-cell keratinizing (LCK) cell type, when applied by the author to tumors with any form of squamous keratinization present, identified a group of patients with a poorer prognosis, although not independently of other prognostic factors. The Stendahl scoring system identified a number of patients with both a poorer and better prognosis. This was statistically significant and independent of other risk factors. A major limitation, however, was the number of patients evaluable because of inadequate biopsy material in 23.6% of the study group. PMID- 8005743 TI - Harnessing D-amino acids for peptide motif designs. Synthesis and solution conformation of Boc-D-Glu-Ala-Gly-Lys-NHMe and Boc-L-Glu-Ala-Gly-Lys-NHMe. AB - In examining the use of D-amino acids in designing specific peptide folding motifs, the tetrapeptide Boc-D-Glu-Ala-Gly-Lys-NHMe 1 and its analog 2 featuring L-Glu were synthesized for a comparison of their solution conformations by NMR spectroscopy. The temperature coefficients of amide proton resonances, NOE data, side-chain CH2 anisotropies and salt titration results suggest a weak type II reverse-turn conformation for peptide 2, and a tandem II' turn-3(10)-helix conformation of appreciable conformational stability for peptide 1 in apolar solvents. The latter is of potential interest as the N-terminal helix cap that could support the design of longer 3(10) helices. Possible origins of appreciable difference in the conformational stabilities of the diastereomers are discussed. PMID- 8005744 TI - Synthesis of a cyclic analogue of the C-loop region of epidermal growth factor, containing 1-aminocyclopropane-1-carboxylic acid. AB - We report the synthesis of a cyclic analogue of epidermal growth factor sequence 33-42 with substitution of 1-aminocyclopropane-1-carboxylic acid for glycine at position 39 (N-acetyl-Cys-Val-Ile-Gly-Tyr-Ser-ACPCA-Asp-Arg-Cys-NH2). The analogue was synthesised by solid-phase methods, using t-Boc chemistry and acid labile side-chain protecting groups. The use of the 4-methoxybenzyl protecting group for C- and N-terminal cysteine residues resulted in the spontaneous formation of the desired intramolecular disulfide bond after HF deprotection. PMID- 8005746 TI - Kinetics of acid-catalyzed degradation of cyclosporin A and its analogs in aqueous solution. AB - The kinetics and mechanism of the degradation of cyclosporin A have been studied under aqueous acidic conditions. The rate of degradation was found to be specific acid-catalyzed over the pH range studied (1-4), with isocyclosporin A as the predominant degradation product. Selective reduction of the olefinic bond of the amino acid 2-N-methyl-(R)-((E)-2-butenyl)-4-methyl-L-threonine (MeBmt) did not affect the overall degradation kinetics and product distribution of cyclosporin A. These observations indicate that the alternative degradation pathway involving intramolecular alkoxy addition to the olefinic bond of amino acid MeBmt apparently does not significantly contribute to the overall degradation kinetics of cyclosporin A in the pH range 1-4. The chemical reactivity of O-acetyl cyclosporin A was examined to probe the governing mechanism for the isomerization of cyclosporin A. Under identical conditions, O-acetyl-cyclosporin A showed a much greater chemical stability than cyclosporin A, consistent with a mechanism involving the hydroxyoxazolidine intermediate. The chemical stability of cyclosporin C, which contains two beta-hydroxyl groups, was also examined. The rate and product distribution for the degradation of cyclosporin C suggest that under aqueous acidic conditions it undergoes N,O-acyl migration solely at the amino acid residue MeBmt. Additionally, the impact of side-chain bulkiness of amino acid MeBmt was examined by studying the degradation kinetics of a series of cyclosporin A analogs.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8005745 TI - Synthetic immunochemistry of glycohexapeptide analogues characteristic of oncofetal fibronectin. Solid-phase synthesis and antigenic activity. AB - Monoclonal antibody FDC-6, and its second-generation antibodies FDB-1 and FDB-4, are able to distinguish between fibronectin (FN) from fetal or cancer tissue (onco-FN) vs. FN from normal adult tissue and plasma (nor-FN). The epitope structure recognized by the above antibodies is the glycohexapeptide H-Val (GalNAc-alpha)Thr-His-Pro-Gly-Tyr-OH (P2). In order to define further the specificity of the reactive site, we synthesized various glycopeptides based on the unglycosylated hexapeptide sequence (P1) and compared their reactivities with these antibodies. In continuation of our structure-activity relationship studies the (Asn3,Ala5)-glycohexapeptide analogue (P3) was synthesized by a solid-phase procedure. The [Ala(CN)3,Ala5]-glycopeptide (P4), owing to dehydration of the asparagine side chain amide during carboxyl activation of Fmoc-Asn-OH, was also isolated. Fmoc-[GalNAc(Ac)3-alpha]Thr-OH was used for incorporating the glycosylated amino acid residue. For the sake of comparison the epitope P2 and the hexapeptide sequence P1 were also synthesized. The final products were characterized by elemental and amino acid analyses, optical rotation, analytical HPLC, proton NMR and fast-atom bombardment mass spectroscopy. Synthetic analogues were applied to inhibit onco-FN specific MAbs FDB-1, FDB-4 and FDC-6 binding to immobilized onco-FN, and their activities were compared with onco-FN and nor-FN. P2 exhibited an activity similar to that of an intact molecule of onco-FN. Deglycosylation (P1) or replacement of amino acid (P3, P4) greatly reduced activity. Data clearly showed that P2 was the minimal essential structure of the epitope in onco-FN defined by MAbs FDB-1, FDB-4 and FDC-6.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8005747 TI - Synthesis and solution structure of an S-glycosylated cyclic hexapeptide. Evidence for conformational change induced by glycosylation. AB - Synthesis and conformational analysis of the S-glycosylated cyclic hexapeptide cyclo(-D-Pro1-Phe2-Cys3(tetra-O-acetyl-beta-D-galactopyranosyl)-++ +Trp4-Lys(Z)5- Phe6-) I was carried out to examine the influence of a saccharide residue in position i of a standard beta-turn on the formation of reverse turns and on the biological activity. Synthesis was carried out in the liquid phase employing a galactosylated cysteine building block. The cyclization reagents DPPA/NaHCO3 avoided high dilution conditions. Spectroscopic data were extracted from homo- and heteronuclear 2D-NMR techniques (TOCSY, NOESY, HMQC, HMQC-TOCSY, HMBCS-270). For structural refinement restrained molecular dynamics (MD) simulations in vacuo and with explicit DMSO as solvent were performed. Finally, simulations in DMSO without experimental restraints provided insight in stability and dynamics of the structural model. A comparison of the S-glycosylated Cys3 peptide with the analogous Thr3 peptide exhibits a similar overall conformation of the hexapeptide [beta II' D-Pro-Phe and another beta-turn about Trp4-Lys5(Z)]. However, the latter shows a distinct dynamic flip beta I, beta II in the glycopeptide, whereas the Thr-analogue only populates beta I. This influence is attributed to a beta I stabilizing effect of a hydrogen bridge of Thr-O gamma in position i to the NH of the amino acid in position i + 2, which is lacking in the glycosylated compound. PMID- 8005748 TI - Conformational study of alanine and alpha-aminoisobutyric psi [NHCO]-retroamide peptide analogues. AB - The minimum-energy conformations of N,N'-dimethyl-2-methylmalondiamide (2mMA) and N,N'-dimethyl-2-dimethylmalondiamide (2dmMA) have been computed using the AM1 method. The results show that molecules tend to form an intramolecular six membered ring hydrogen-bond system. The same trend is observed in crystals of malonamide derivatives substituted in the central carbon atom. The results are also compared with previous molecular-mechanics calculations. The conformational trends of 2mMA and 2dmMA are very similar to those showed by N,N' dimethylmalondiamide. Details of the computed conformational energy maps for 2mMA and 2dmMA compounds are given. PMID- 8005749 TI - Structural investigation of Cetrorelix, a new potent and long-acting LH-RH antagonist. AB - The new decapeptide SB-75 (INN: Cetrorelix) has been characterized as a potent antagonist of luteinizing-hormone releasing hormone (LH-RH). Such derivatives are of great medicinal interest owing to their potential application in areas such as hormone-dependent tumors, uterine fibroids, and in diseases and conditions which result from inappropriate hormone levels or which can be treated by suppression of estrogens. SB-75 is the subject of intensive ongoing clinical evaluation and is an accepted standard for the design of new LH-RH antagonists. We characterized SB-75 by means of modern MS and NMR techniques to demonstrate the significance of both sequencing methods on a complicated unnatural decapeptide. Our structural elucidations with nuclear Overhauser (NOE) experiments revealed clear evidence for a highly flexible molecule with no single predominant conformation even in sodium dodecyl sulfate (SDS) mimicking a cellular membrane. PMID- 8005750 TI - Conformation of a biologically active C-terminal hexapeptide analog of the pheromone biosynthesis activating neuropeptide by NMR spectroscopy. AB - The solution conformation of a biologically active C-terminal hexapeptide analog of the pheromone biosynthesis activating neuropeptide Tyr-D-Phe-Ser-Pro-Arg-Leu NH2 has been studied by NMR spectroscopy. A beta-turn conformation was identified from the NOE connectivities observed for the peptide in a mixed solvent of water and DMSO, indicating that this is the biologically active conformation of the peptide. This study also suggests that the use of such an aqueous-like solvent mixture allows the observation of a preferred conformation for small linear peptides in the presence of conformational averaging. PMID- 8005751 TI - Conformations of arginine and lysine side chains in association with anions. AB - The side chain conformations shown by arginine and lysine in amino-acid and peptide crystal structures and bound to oxyanions in proteins have been analyzed in an attempt to understand the behaviour of these long-chain amino acids in an ionic environment. Except for chi 1, torsions have a preference for the trans conformation. However, for arginine in protein structures, chi 3 and chi 4 appear to be flexible and can be tuned for optimal anion binding. For chi 4, values in the range -80 to 80 degrees are excluded for steric reasons; the remaining region in conformational space is accessible. This orientational variety exhibited by chi 4 has not been hitherto appreciated. Factors that can forbid a chi-angle to be in the trans geometry are the simultaneous binding of the anion by the main- and side-chain atoms, or the sharing of the anion between two different molecules in the crystal structure. Small molecules containing arginine have a distinct tendency to crystallize with two molecules in the asymmetric unit. This may be a general phenomenon for all extended molecules which have hydrogen-bond donors (or acceptors) embedded in a rigid set-up. PMID- 8005752 TI - Side-product formation during cyclization with HBTU on a solid support. AB - The coupling reagent 2-(1H-benzotriazol-1-yl)-1,1,3,3-tetramethyluronium hexafluorophosphate (HBTU) was used in an attempt to prepare a highly strained 10 membered lactam ring on a solid support via side-chain to side-chain cyclization of the adjacent alpha,gamma-diaminobutyric (Dab) and D-glutamic acid residues in [Dab2,D-Glu3,Leu5]enkephalinamide. This attempted cyclization failed, however, and yielded linear products instead. Characterization by mass spectrometry, amino acid analysis, peptide sequencing and NMR indicated that the major products were the tetramethylguanidinium (Tmg) derivatives [Dab(Tmg)2,D-Glu3,Leu5] enkephalinamide and the corresponding dimeric linear Tmg-containing peptide which resulted from the transfer of the tetramethyluronium moiety from HBTU to the amino side chain of Dab. The formation of these tetramethylguanidinium side products during cyclization reactions limits HBTU's usefulness for the formation of lactams. PMID- 8005753 TI - Synthesis and protease-catalyzed hydrolysis of a novel hydrazinopeptide. AB - In order to explore the potentiality of hydrazinopeptides as protease inhibitors, the resistance of the hydrazinopeptidic bond toward proteolysis was investigated. To this end, the novel hydrazinohexapeptide Z-Ala2-Pro-Val-hIle-Leu-OMe (1), where hIle represents hydrazinoisoleucine, was designed and synthesized together with the parent peptide Z-Ala2-Pro-Val-Ile-Leu-OMe (2). The interactions of 1 and 2 with human leukocyte elastase (HLE) and porcine pancreatic elastase (PPE) were analyzed comparatively. We observed that 1 behaved as a substrate for both elastases, without the formation of a stable acyl-enzyme as in the case of azapeptides. Compounds 1 and 2 were cleaved at the same site (-Val-parallel-NH-) with a slight delay of hydrolysis for 1 compared to 2 (kcat/KM for 1 vs. 2 decreased by a factor of 2.7 for the HLE-catalyzed hydrolysis at pH 8.0 and 25 degrees C). The presence of the hydrazinopeptide bond (-CONHNH-) in 1 reduced by a factor of 4.7 the apparent enzyme affinity without abolishing it. These results indicate that suitably designed hydrazinopeptides may represent interesting targets in the search for protease resisting pseudopeptides. PMID- 8005754 TI - Crystal structure analysis of a beta-turn mimic in hydrazino peptides. AB - The crystal structures of four hydrazino peptides (Piv-Pro-h(N alpha-Bzl)Gly NHiPr 1, Piv-Pro-hAla-NHiPr 2, Moc-hPro-NHiPr 3, and Boc-hPro-Gly-N(OH)Me 4) deriving from the hydrazino analogues of glycine (hGly), L-alanine (hAla) or L proline (hPro) have been solved. They reveal a common folded structure of the alpha-hydrazino acid residue characterized by a bifurcated hydrogen bond closing an eight-membered cycle. This folded structure is topologically similar to the beta II'-turn in peptides, and the CO-NH-N hydrazide link can be considered as a good turn-inducer in peptide analogues. PMID- 8005755 TI - The concept of superactive esters. Could peptide synthesis be improved by inventing superactive esters? AB - According to the concept presented, esters forming an amide (peptide) bond by the mechanism SN#DN or SN#*DN involving fast decay of the tetrahedral intermediate may behave as 'superactive acylating reagents'. These should render coupling involving less reactive substrates, i.e. sterically hindered or 'difficult coupling sequences', much faster and more uniform than classic active esters. In extremely cases this advantage could be significant, and the calculated increase in time required for 99.9% coupling substrates 6 pKa units less reactive than the standard ones reaches 2,512,000 tau 1/2 units for classic active esters, but only 631 tau 1/2 units for reaction involving 'superactive esters'. The postulated change of mechanism is expected for esters bearing a leaving group which is able to undergo an additional, synchronous, energetically favored process accompanying its departure, as has been observed in the case of triazine esters. Some advantages of triazine superactive esters in the condensation of sterically hindered substrates are demonstrated. PMID- 8005756 TI - Schopenhauer and Freud. AB - A close study of Schopenhauer's central work, 'The World as Will and Representation', reveals that a number of Freud's most characteristic doctrines were first articulated by Schopenhauer. A thinker always expresses something of his culture, of course, but the parallels to be found between Freud and Schopenhauer go well beyond cultural influence. Schopenhauer's concept of the will contains the foundations of what in Freud became the concepts of the unconscious and the id. Schopenhauer's writings on madness anticipate Freud's theory of repression and his first theory of the aetiology of neurosis. Schopenhauer's work contains aspects of what become the theory of free association. And most importantly, Schopenhauer articulates major parts of the Freudian theory of sexuality. These correspondences raise some interesting questions about Freud's denial that he even read Schopenhauer until late in life. PMID- 8005757 TI - The failed and the inadvertent: art history and the concept of the unconscious. AB - The history of art-historical responses to psychoanalysis has yet to be written. Art historians have imported a wide variety of psychoanalytic concepts, and psychoanalysis continues to be a major interpretive resource for the discipline of art history. But beyond the core of art-historical texts that are directly and explicitly influenced by psychoanalysis is a much larger, and I think more important, class of texts that do not cite psychoanalytic concepts, but would nevertheless not be possible without psychoanalysis and especially the fundamental concept of the unconscious. This paper examines the ways that the idea (or notion) of the unconscious affects current thinking about the control artists have over their works; I argue that, in this more general sense, psychoanalysis has tended to help art historians to take away artists' control and awareness of their own work, replacing it with the model of artists as workers largely unaware of what they do. Against this I argue that artists who are imagined to 'preside over their work with their eyes open' can be more interesting subjects, both historically and psychologically. PMID- 8005758 TI - A psychoanalyst's reflections on Chekhov and Three Sisters. AB - The author has given some of his reflections on one of Anton Chekhov's greatest works, the late play Three Sisters. The paper considers the origins of the central concerns of Chekhov's life in a childhood beset by trauma and physical and emotional deprivation, the effects of which he partially overcame through genius and rigorous self-examination and self-discipline. As one examines the plot of this play, one can appreciate the complexity of the playwright's position -delicately and mysteriously suspended between the role of scientific observer of the human condition, while also passionately involved, empathically and morally, in the the inner worlds of both men and women, the young and old, people often trapped within their personal limitations and the social, economic and political worlds they inhabit. PMID- 8005759 TI - Karl A. Menninger (1893-1990). PMID- 8005760 TI - Farewell to the objective analyst. AB - The objective analyst is one who can stand outside of any given situation and make neutral observations, providing his or her countertransference feelings are in hand. The argument against such objectivity offered in this paper is that the activity of analysis involves both prejudice, i.e. one's pre-set ideas, and participation, i.e. a necessary and inevitable change in oneself. Therefore we all see things a bit differently, and we are all effected differently by what we see. Such a view of analysis forces us to insist upon limiting its practice to the analytic setting as well as calling for a recognition of our own subjective states which go beyond countertransference and encompass our whole selves. Since we are never context-free we must recognise that our interpretations are never able to be limited to one fixed reading and so the exchange between patient and analyst is always open and continuous. PMID- 8005761 TI - The analytic third: working with intersubjective clinical facts. AB - In this paper, two clinical sequences are presented in an effort to describe the methods by which the analyst attempts to recognise, understand and verbally symbolize for himself and the analysand the specific nature of the moment-to moment interplay of the analyst's subjective experience, the subjective experience of the analysand and the intersubjectively-generated experience of the analytic pair (the experience of the analytic third). The first clinical discussion describes how the intersubjective experience created by the analytic pair becomes accessible to the analyst in part through the analyst's experience of 'his own' reveries, forms of mental activity that often appear to be nothing more than narcissistic self-absorption, distractedness, compulsive rumination, daydreaming and the like. A second clinical account focuses on an instance in which the analyst's somatic delusion, in conjunction with the analysand's sensory experiences and body-related fantasies, served as a principal medium through which the analyst experienced and came to understand the meaning of the leading anxieties that were being (intersubjectively) generated. PMID- 8005762 TI - How the analyst listens: the pre-stages of interpretation. AB - There has been little systematic treatment of the pre-stages of interpretation that include the process of analytic listening itself, and the gathering and sorting of information that could lead to the formulation of an interpretation. The situation of the analyst as listener is compared with that of the social listener, and the focus is on processes close to the surface of experience. Three 'modes' of listening are described that must be continuously available to the analyst, and which taken together capture the sense of 'evenly hovering attention'. The use and misuse of the concept of empathy in relation to analytic listening are discussed. PMID- 8005763 TI - On knowing the unconscious: lessons from the epistemology of geometry and space. AB - Concepts involving unconscious processes and contents are central to any understanding of psychoanalysis. Indeed, the dynamic unconscious is familiar as a necessary assumption of the psychoanalytic method. Using the manner of knowing the geometry of space, including non-ordinary sized space, this paper attempts to demonstrate by analogy the possibility of knowing (and knowing the nature of) unconscious mentation-that of which by definition we cannot be aware; and yet that which constitutes a basic assumption of psychoanalysis. As an assumption of the psychoanalytic method, no amount of data from within the psychoanalytic method can ever provide evidence for the existence of the unconscious, nor for knowing its nature; hence the need for this sort of illustration by analogy. Along the way, three claims are made: (1) Freudian 'secondary process' operating during everyday adult, normal, logical thought can be considered a modernised version of the Kantian categories. (2) Use of models facilitates a generation of outside-the-Kantian-categories possibilities, and also provides a conserving function, as outside-the-categories possibilities can be assimilated. (3) Transformations are different from translations; knowledge of transformations can provide non-trivial knowledge about various substrates, otherwise difficult to know. PMID- 8005764 TI - Change in psychoanalysis: epistemological aspects. AB - The paper addresses the objectives of therapeutic work, emphasising processes of change which move an 'inadequate' state towards another, more 'adequate' one. Different types of change are considered, and the factors necessary for detecting them. Following the mathematical model, we distinguish between continuous and discontinuous change. In social processes also there are continuous changes, where a transition occurs cumulatively and slowly. In another type of change a drastic modification is produced, implying discontinuity and a sudden jump. On this point it is necessary to distinguish between removable discontinuities having little significance, and essential ones which have significant effects. 'Levels of change' imply categorical or structural differences. We consider different forms of obstacle which get in the way of the adequate management of change: non-perception of change on the part of the therapist, epistemological inertia and therapeutic zeal. We address the location of change in the psychoanalytic process in relation to the patient-analyst couple. PMID- 8005765 TI - The invisible woman. AB - This paper explores the meaning of experiences of invisibility in women. It was inspired in the course of psychotherapy with a woman who felt invisible in her feminine identity and who hid her feminine desire within an imaginary paper bag. Her visual imagery traces a pattern of pathological feminine development through a faulty sensory connection between her body, the external world, and her unconscious symbolic self-representation. Questions about her invisibility have evoked an exploration of two developmental models of visual thinking--a cognitive and a psychoanalytic model. A study of the myth of Persephone contributes a literary prototype for the understanding of the transmission of invisibility across the generations of mothers and daughters. Furthermore, the analysis of several literary passages from the work of Angela Carter serves the purpose of drawing the reader into the experiential world of femininity as it moves from the invisible to the visible. The paper blends together ideas from various, often contending, theorists in a way which highlights how theories can complement one another in explaining clinical phenomena. PMID- 8005766 TI - Transference: erotised, erotic, loving, affectionate. AB - Within a set of phenomena traditionally problematic for psychoanalysis, four types of erotic transference are outlined with a description of their dynamic genesis and related case histories (transference and countertransference developments, fundamental treatment procedures): erotised, erotic, loving, and affectionate transference. The first type is based mostly on psychotic modalities, the second on neurotic modalities. Both the loving and the affectionate transference, on the other hand, turn out to be clinical forms corresponding to a normal substantially same development, different from each other by virtue of a diverse level of maturation in the Oedipus complex: they often provoke--in analysts--a defensive stiffening which is harmful and--from the theoretical point of view--not above reproach. The work is particularly focused on the analytic evolution of a female patient who develops an amorous transference in which the defensive aspects prove to be less important than the potentially evolutionary ones. The treatment has been based--in particular--on the analytic utilisation of this transference. The last part of the contribution is devoted to the analysts' 'guarantee factors', which permit them to work in psychoanalysis with the 'highly explosive forces' of these transference configurations, maintaining a useful, rigorous, sensitive and sufficiently creative framework. PMID- 8005767 TI - Two empirical notes on Freud's Leonardo. AB - Why did Freud, in his Leonardo study, speak of a vulture instead of a kite (in Italian nibbio)? It can be shown that contemporary dictionaries rendered nibbio by Huhnergeier; that this designation of the kite was unfamiliar in Standard German; but that it was automatically understood as referring to a sub-species of Geier (vulture). Freud had an anachronistic idea about non-marital sex relations in quattrocento Italy. Such liaisons were not uncommon between higher-ranking males and lower-ranking females, their offspring were assigned to the paternal family. Leonardo's mother probably served as wetnurse for her illegitimate son, returning him to his father and being married to a man of equal standing after the customary time of weaning (ca. 18 months). Concerning Leonardo's psycho sexual development, the corrected data shift the emphasis from the oedipal level (Freud) to an earlier, ambivalent mother-child relation (Eissler). Both notes warn against some pitfalls of psychobiography. PMID- 8005768 TI - The utilization of rubber dam as a barrier membrane for the simultaneous treatment of multiple periodontal defects by the biologic principle of guided tissue regeneration: case reports. AB - The principle of guided tissue regeneration has demonstrated a level of success in regenerating the periodontal attachment apparatus lost to periodontal disease. Several types of membrane barriers, each one with distinct properties, have been utilized to apply this principle in periodontal wound healing. A series of case reports introduces and discusses the attributes of rubber dam as a barrier membrane for the treatment of multiple periodontal osseous defects. Comparison of preoperative and postoperative clinical measurements as well as reentry procedures are utilized to highlight successful osseous regeneration. PMID- 8005769 TI - Form and color reproduction for composite resin reconstruction of anterior teeth. AB - To obtain esthetic results with composite resin restorations, it is necessary to consider the following elements: the structure of composite resin; tint modifiers; opaquers; generic form; and surface texture. This article discusses these elements and presents clinical examples of techniques for achieving esthetic composite resin restorations. PMID- 8005770 TI - Localized ridge augmentation using absorbable pins and e-PTFE barrier membranes: a new surgical technique. Case reports. AB - This paper presents a new surgical technique to promote bone formation in localized alveolar ridge defects. The objective was to regenerate sufficient bone volume for implant placement. The technique is dependent on careful defect debridement and the use of absorbable orthopedic pins, which serve as tent poles and prevent the e-PTFE barrier membranes from collapsing into the defects. The three defects treated with this technique were completely resolved with new bone, and implants were successfully placed into the augmented ridges. Biopsies from the treated sites revealed new bone formation. PMID- 8005771 TI - Effect of root conditioning on periodontal wound healing with and without guided tissue regeneration: a pilot study. II. Autoradiographic evaluation. AB - This investigation deals with the proliferation and migration of the progenitor cells during the healing of closed periodontal wounds. Periodontal surgical defects affecting the bone and dentin were created in four mongrel dogs. The defects were treated with topical applications of citric acid, tetracycline, or sterile water with and without the placement of nonresorbable membranes. The dogs were killed at 1, 3, 7, and 21 days after surgery. One hour before they were killed, they were intravenously injected with tritiated thymidine. Tissues were processed and routinely prepared for autoradiographic studies. Labeled cells were counted at the apical, coronal, and central areas of the defects. Results suggested that the citric acid and tetracycline treatments inhibited cellular proliferation at the initial time periods of 1 and 3 days. At 7 and 21 days, differences between citric acid and tetracycline treatments were minimal, and neither showed any advantage over the application of sterile water. The placement of the nonresorbable membrane demonstrated a trend of increased labeling at 21 days for all three treatments. PMID- 8005772 TI - The importance of restorative margin placement to the biologic width and periodontal health. Part II. AB - Part I of this article presented the rationale for the use of the crown lengthening procedure prior to final prosthetic or restorative treatment. The primary objective of the procedure is the attainment of a periodontal biologic width, free of any invasive restorative dentistry, circumferentially around the tooth. Part II of this article presents a clinical case to demonstrate, step by step, the crown-lengthening procedure. Concurrently the clinical rationale for these steps is also explained. PMID- 8005773 TI - Guided tissue regeneration with a rubber dam: a five-case report. AB - Five cases are presented to document the use of an unusual barrier in the treatment of infrabony defects according to the principles of guided tissue regeneration. A rubber dam was positioned after flap elevation, defect debridement, and root planing to cover the defect and the surrounding bone. The dam was covered with the surgical flap and removed after 5 weeks. The 1-year clinical measurements and reentry procedure demonstrated the efficacy of the rubber dam as a barrier in guided tissue regeneration procedures. PMID- 8005774 TI - Psychiatric rehabilitation: redefined for the 1990s. PMID- 8005775 TI - Posttraumatic stress disorder among Cambodian refugees in New Zealand. AB - The author's objective was to determine the amount of trauma, prevalence and diagnostic features of posttraumatic stress disorder (PTSD), and to study the relationship between PTSD and demographic variables, trauma experiences, coping style and post-migration stresses among adult Cambodian refugees in New Zealand. Information on basic sociodemographic data, trauma experiences, posttraumatic stress symptoms, General Health Questionnaire 28-item version (GHQ-28) scores, coping style, and post-migration stresses were gathered from 223 adult Cambodian refugees living in Dunedin, New Zealand. Most subjects had experienced multiple, severe traumas. The prevalence of PTSD was 12.1%. The most frequently reported posttraumatic stress symptom was recurrent intrusive recollection of trauma. There was a significant association between PTSD and amount of trauma, coping style, and post-migration stresses. PMID- 8005776 TI - Attitudes towards the work behaviour of ex-mental patients in Nigeria. AB - Attitudes towards the work behaviour of ex-mental patients were examined in a random sample of 480 senior federal civil servants in Nigeria. The results revealed: pervasive negative attitudes towards ex-mental patients and their work behaviour; inadequate provision for the needs of ex-mental patients by government; lack of awareness of and/or non-existence of welfare policies for rehabilitating ex-mental patients; and a need for a social welfare policy to cater for ex-mental patients in the workplace. PMID- 8005777 TI - Chinese American adults' relationship with their parents. AB - This investigation examines the relationship between Chinese American adults and their parents. A group of 143 American- and foreign-born Chinese Americans residing in San Francisco participated in the study. Contact with parents was found to be very frequent (two to three times a week), and was primarily mediated by geographic proximity. Immigrant women maintained significantly more frequent contact with their parents than American-born women. Intimacy was primarily predicted by respondent's understanding of his/her mother. Implications of the findings are discussed. PMID- 8005778 TI - The social psychology of 'epidemic' koro. AB - The few isolated reports of individual koro exhibit a symptomatology indicative of major psychiatric conditions (ie. psychosis or affective disorder), and appear unrelated to collective episodes which involve social, cultural, cognitive and physiological factors in the diffusion of koro-related beliefs. Yet, koro 'epidemics' continue to be viewed as exemplifying mass psychopathology or irrationality. An examination of the similarities between koro 'outbreaks' and a sub-category of behaviour which has been loosely labeled as 'mass hysteria', suggests an alternative, non-psychopathological explanation. In reclassifying 'epidemic' koro as a collective misperception rather than a culture-bound syndrome, it is argued that koro is a rational attempt at problem-solving which involves conformity dynamics, perceptual fallibility and the local acceptance of koro-associated folk realities, which are capable of explaining such episodes as normal within any given population. PMID- 8005779 TI - The unique challenges faced by psychiatrists and other mental health professionals working in a multicultural setting. AB - This article describes and analyzes the unique challenges that face psychiatrists and other mental health professionals serving a multicultural population in a limited geographic setting, based on the author's experiences working as a psychiatrist on a mobile crisis unit from 1984 through 1991 on the Lower East Side of Manhattan. Of special importance, the paper presents and provides support for the "interaction hypothesis", which proposes that sociocultural background factors interact with mental disorders to produce dissimilar behavioral expressions of the same disorder among members of different ethnic groups. Concern is voiced that mental health professions, in order to provide effective treatment in multicultural settings, need to understand and accept each ethnic group's idiosyncracies, identity, and background. PMID- 8005780 TI - Organ transplantation overview. PMID- 8005781 TI - 25 years of kidney transplantation in Hawaii. AB - The first kidney transplant in Hawaii was performed in August 1969. In the following 25 years, more than 433 kidney transplants were performed. The most common etiology leading to transplantation was chronic glomerulonephritis. Patient and graft survivals after a kidney transplant have progressively improved, particularly after the introduction of cyclosporine in 1984. The overall one-year patient and graft survival rates now are 96% and 85%, respectively; these results exceed the national averages. PMID- 8005782 TI - Cardiac transplantation in Hawaii. AB - Clinical cardiac transplantation was successfully introduced 26 years ago, and from an initial experimental status, it has moved forward to become an accepted and well-established treatment modality for end-stage cardiac disease. The first cardiac transplant operation in Hawaii was performed in March 1987; the patient lived for 1 year. A total of 20 heart transplant operations have been performed in 19 patients at St. Francis Medical Center in Honolulu. There has been only one hospital death, and our current one-year survival is 77%, which is similar to national statistics. Our longest survivor is now more than 6 years following transplantation. The incidence of rejection episodes and infectious complications is comparable to other studies. PMID- 8005783 TI - Liver transplantation in Hawaii. AB - The first liver transplant performed in Hawaii was on May 17, 1993 in a patient with end-stage liver disease caused by autoimmune hepatitis. Liver transplantation is a well-accepted treatment for end-stage liver disease with a 1 year patient survival of 80% to 85%. Early recognition of the appropriate candidate by primary care physicians and prompt referral to a liver transplant center are essential for optimal results. The indications, contraindications, organ procurement and allocation, complications, and results of liver transplantation are described. Finally, several controversial areas will be introduced, including liver transplant for alcoholic cirrhosis and hepatitis B, and use of transjugular intrahepatic portosystemic shunts (TIPS). PMID- 8005784 TI - Pancreas transplantation for diabetic patients in Hawaii. AB - Diabetes mellitus is a common disease affecting a large population in Hawaii. Over the past 20 years, pancreas transplantation has evolved into a viable therapeutic option for selected patients with diabetes mellitus. This report describes the first combined pancreas-kidney transplant performed in Hawaii on June 28, 1993 on a patient with juvenile-onset diabetes mellitus and diabetic nephropathy. The patient has remained off insulin and off dialysis since the transplant. The history, indications, techniques, and potential complications related to this procedure are discussed. PMID- 8005785 TI - The need for organ donation in Hawaii. AB - Donor organ availability is the primary limiting factor in organ transplantation. The number of patients on the national organ waitlist has increased to more than 32,000, while the number of donors has remained fairly constant at approximately 4,500 per year. In Hawaii, there are 98 patients awaiting organ transplants, and for the past 5 years, the average number of donors per year was 15. The criteria for organ donation, brain death, approaches to donation request, and the management of the multiple organ donor are discussed. PMID- 8005786 TI - Ethnic differences in use of inpatient mental health services by blacks, whites, and Hispanics in a national insured population. AB - OBJECTIVE: We examine whether ethnic differences in use of inpatient mental health services exist when the usually confounding effects of minority status and culture are minimized or controlled. DATA SOURCES AND STUDY SETTING: Secondary analyses were conducted using a national insurance claims database for 1.2 million federal employees and their dependents insured by the Blue Cross/Blue Shield (BC/BS) Federal Employees Plan (FEP). STUDY DESIGN: The Andersen-Newman model of health utilization was used to analyze predisposing, enabling, and need variables as predictors of inpatient mental health utilization during 1983. The study design was cross-sectional. DATA COLLECTION: The study database was made up of BC/BS insurance claims, Office of Personnel Management employee data, and Area Resource File data. PRINCIPAL FINDINGS: No significant differences were found among blacks, whites, and Hispanics in the probability of a psychiatric hospitalization or in the number of inpatient psychiatric days. Regression analyses revealed younger age and psychiatric treatment of other family members as significant predictors of a hospitalization; region of residence, younger age, hospital bed availability, and high option plan enrollment were significant predictors of the number of treatment days. CONCLUSIONS: Ethnic differences in use of inpatient mental health services were not significant in this generously insured population. Further research involving primary data collection among large and diverse samples of ethnic individuals is needed to fully examine the effects of cultural and socioeconomic differences on use of mental health services. PMID- 8005787 TI - An analysis of the costs and benefits of two strategies to decrease length of stay in children's psychiatric hospitals. AB - OBJECTIVE: We analyze the costs and benefits of two strategies-intensive home based services and increased remuneration for providers of community-based placements--to decrease excessive length of stay in a children's psychiatric hospital. DATA SOURCES AND STUDY SETTING: Clinical, demographic, and financial data were collected retrospectively on all children discharged during 1987 through 1989 from the state children's psychiatric hospital that serves Wayne County, Michigan. Characteristics of the discharged children were similar to those reported in other studies of intensive home-based services. STUDY DESIGN: A sample of 22 children was used for a simulation analysis. Excessive length of stay was defined as the duration of hospitalization after readiness for discharge and associated planning were indicated in the record. For the simulated analysis of the intensive home-based program, costs included estimated charges for the program and charges for the children hospitalized due to failure of the intervention. For analysis of the increased remuneration strategy, costs included charges for the out-of-home placement and charges for hospitalization. For both strategies benefits were defined as averted hospitalization charges. DATA COLLECTION/EXTRACTION METHODS: Charts of the discharged children were reviewed and 21 clinical, demographic, and financial variables were extracted. PRINCIPAL FINDINGS: Analysis of costs and benefits of intensive home-based services produced a favorable cost-benefit ratio of .47. Analysis of the strategy to increase remuneration for providers of community-based placements resulted in a cost-benefit ratio of 1, indicating no financial savings. CONCLUSIONS: Intensive home-based services represent an efficient strategy to decrease excessive length of stay for children in psychiatric hospitals by averting hospitalization altogether. Although increased remuneration to providers of community-based placements in order to increase the supply of placements as a means to hasten discharge from the hospital has a neutral cost-benefit ratio, the opportunity to provide care in the "least restrictive" environment argues in its favor as well. PMID- 8005788 TI - Determinants of the use of specialist mental health services by nursing home residents. AB - OBJECTIVE: This study examines the effects of resident and facility characteristics on the probability of nursing home residents receiving treatment by mental health professionals. DATA SOURCES/STUDY SETTING: The study uses data from the Institutional Population Component of the 1987 National Medical Expenditure Survey, a secondary data source containing data on 3,350 nursing home residents living in 810 nursing homes as of January 1, 1987. STUDY DESIGN: Andersen's health services use model (1968) is used to estimate a multivariate logistic equation for the effects of independent variables on the probability that a resident has received services from mental health professionals. Important variables include resident race, sex, and age; presence of several behaviors and reported mental illnesses; and facility ownership, facility size, and facility certification. DATA COLLECTION/EXTRACTION METHODS: Data on 188 residents were excluded from the sample because information was missing on several important variables. For some additional variables residents who had missing information were coded as negative responses. This left 3,162 observations for analysis in the logistic regressions. PRINCIPAL FINDINGS: Older residents and residents with more ADL limitations are much less likely than other residents to have received treatment from a mental health professional. Residents with reported depression, schizophrenia, or psychoses, and residents who are agitated or hallucinating are more likely to have received treatment. Residents in government nursing homes, homes run by chains, and homes with low levels of certification are less likely to have received treatment. CONCLUSIONS: Few residents receive treatment from mental health professionals despite need. Older, physically disabled residents need special attention. Care in certain types of facilities requires further study. New regulations mandating treatment for mentally ill residents will demand increased attention from nursing home administrators and mental health professionals. PMID- 8005789 TI - Strategic groups, performance, and strategic response in the nursing home industry. AB - OBJECTIVE: This study examines the effect of strategic group membership on nursing home performance and strategic behavior. DATA SOURCES AND STUDY SETTING: Data from the 1987 Medicare and Medicaid Automated Certification Survey were combined with data from the 1987 and 1989 Pennsylvania Long Term Care Facility Questionnaire. The sample consisted of 383 Pennsylvania nursing homes. STUDY DESIGN: Cluster analysis was used to place the 383 nursing homes into strategic groups on the basis of variables measuring scope and resource deployment. Performance was measured by indicators of the quality of nursing home care (rates of pressure ulcers, catheterization, and restraint usage) and efficiency in services provision. Changes in Medicare participation after passage of the 1988 Medicare Catastrophic Coverage Act (MCCA) measured strategic behavior. MANOVA and Turkey HSD post hoc means tests determined if significant differences were associated with strategic group membership. FINDINGS: Cluster analysis produced an optimal seven-group solution. Differences in group means were significant for the clustering, performance, and conduct variables (p < .0001). Strategic groups characterized by facilities providing a continuum of care services had the best patient care outcomes. The most efficient groups were characterized by facilities with high Medicare census. While all strategic groups increased Medicare census following passage of the MCCA, those dominated by for-profits had the greatest increases. CONCLUSIONS: Our analysis demonstrates that strategic orientation influences nursing home response to regulatory initiatives, a factor that should be recognized in policy formation directed at nursing home reform. PMID- 8005790 TI - The standard gamble method: what is being measured and how it is interpreted. AB - OBJECTIVE: The Standard Gamble (SG) technique is recommended for measurement of individuals' preferences under uncertainty and to express the outcome of different therapeutic choices in utility values to be used in clinical decision analysis and health program evaluation. The article alerts users of this technique to problems stemming from inappropriate interpretation of results of measurements using the SG method. STUDY DESIGN: We review different situations where the SG method is used to measure individuals' or group preferences. PRINCIPAL FINDINGS: We demonstrate inappropriate interpretation of the time dimension at the individual level; issues stemming from the aggregation of individual utility values measured using different time horizons; the potential for double counting of the time preference effect when discounting future quality adjusted life years (QALYs); and problems associated with using the SG technique to measure temporary health states. CONCLUSIONS: The inappropriate interpretations stem mainly either from ignoring the time dimension, which is inextricably bound to the health of the individual, or form adding assumptions, in addition to those required by von Neumann-Morgenstern (vNM) utility theory, that are not supported by empirical evidence. An alternative approach to QALYs, the healthy years equivalent (HYE), which incorporates the SG but avoids many of these problems, is described. PMID- 8005792 TI - Encrypting personal identifiers. AB - STUDY SETTING. A statewide patient discharge database contained only one unique identifier: the social security number (SSN). A method was developed to transform (encrypt) the SSN so that it could be made publicly available, for purposes of linking discharge records, without revealing the SSN itself. The method of encrypting the SSN into a Record Linkage Number (RLN) is described. PRINCIPAL FINDINGS. The same RLN will always result from the same SSN; it is highly improbable that the same RLN would be produced by two different SSNs; the SSN cannot be derived from the RLN, even given access to the encryption program; the encryption method cannot be determined through knowledge of a number of SSN/RLN combinations; and the method can be described, evaluated, and adapted for use by other researchers without compromising confidentiality of the RLNs resulting from the method. PMID- 8005791 TI - Utilization patterns of cohorts of elderly clients: a structural equation model. AB - OBJECTIVE: To identify a model that takes into account the interrelationship of health services utilization variables, and that allows examination of the utilization patterns of health services for a cohort of elderly clients. DATA SOURCES AND STUDY SETTING: The data of each client in the study were taken from three computer databases maintained for administrative purposes by the Ministry of Health in British Columbia. Time frame for the utilization variables is one year before and one year after admission to the long-term care program in BC which occurred in 1981-1982. STUDY DESIGN: A basic model was fitted to the utilization data for the year before admission and patterns of utilization were assessed for each gender-age group for the year before admission and for the two periods, using LISREL: Fifteen utilization variables were included: number of GP and specialist visits in different settings (office, home, etc.) and number of other services such as lab tests, hospital stay, etc. DATA COLLECTION: The three files were linked to produce one record per client. PRINCIPAL FINDINGS: A model was identified that fits the data well. The total effect of GP emergency room visits on hospital stay is 0.30 compared to 0.19 direct effect. The additional impact is produced via the effect of specialist consultations on hospital stay. This and similar findings by age, gender, and period are consistent with the joint dependency of utilization variables. CONCLUSIONS: The analysis shows that males and females have different utilization patterns, while age has no effect on utilization of health services by male clients and only a small effect on utilization patterns by female clients. Admission to LTC causes more specialist contacts resulting from contact with a GP and generally a more intensive use of diagnostic and surgical procedures. However, there is significantly less acute care hospital services utilization. PMID- 8005793 TI - In vivo electron paramagnetic resonance spectroscopy-imaging in experimental oncology: the hope and the reality. AB - PURPOSE: Low frequency (280 MHz) electron paramagnetic resonance imaging is a new magnetic resonance technique, still being developed, that can map the in vivo spatial distribution of paramagnetic species such as nitroxide free radicals. The reduction rate of these molecules is affected by oxygen concentration. This paper gives some examples of the use of electron paramagnetic resonance imaging methodology in whole rats in the framework of its possible use in experimental oncology. METHODS AND MATERIALS: The 280 MHz apparatus based on a cylindrical 16 pole magnet was developed and designed specifically for 50-200 g laboratory animals. It generates the main field and the three field gradients required for three-dimensional (3-D) projections. A pyrrolidine nitroxyl (2,2,5,5, tetramethylpyrrolidine-1-oxyl-3-carboxylic acid) was injected intravenously in rats to provide an electron paramagnetic resonance signal for in vivo measurements. Electron paramagnetic resonance X-band spectrometer was used to monitor pyrrolidine nitroxyl decay in an external blood circuit during normoxia and moderate hypoxia (15% O2). RESULTS AND CONCLUSION: One-dimensional (1-D) transversal and longitudinal mapping of this nitroxide free radical distribution in rat whole body was obtained 7-9 min after injection. In circulating blood, nitroxide half-life decreased significantly during hypoxia. The present sensitivity (10(-4)-10(-5) M), spatial resolution (3-10 mm) and collection time (3-5 min) could be drastically improved by narrow linewidth paramagnetic probes and pulsed techniques. PMID- 8005794 TI - Direct measurement of pO2 distribution and bioreductive enzymes in human malignant brain tumors. AB - PURPOSE: To measure the oxygen status of human malignant brain tumors in vivo and to determine the activities and expression of bioreductive enzymes in these same human brain tumor samples, as a means of assessing their suitability as targets for bioreductive drug therapy. METHODS AND MATERIALS: A polarographic oxygen electrode was used to measure the intratumoral oxygen tension in twenty patients with malignant brain tumors during open brain surgery, performed under standard anaesthetic conditions. Six different tracks, each with a path length of 22 mm, were recorded per patient representing 192 readings. Following pO2 measurements the tumors were resected and stored in liquid N2 for subsequent bioreductive enzyme analysis. Eight human malignant brain tumors were assessed, by enzyme activity and western blot expression, for the presence of various bioreductive enzymes. These enzymes included DT-diaphorase, NADH cytochrome b5 reductase, and NADPH cytochrome P-450 reductase. Of these eight gliomas analyzed six samples were incubated with the bioreductive drug tirapazamine, in the presence of cofactor(s), to establish whether human brain tumors could metabolize this compound. RESULTS: Both the high grade intrinsic and metastatic brain tumors showed significant regions of hypoxia. All the tumors subjected to enzyme profiling contained the bioreductive enzymes, DT-diaphorase, NADH cytochrome b5 reductase and NADPH cytochrome P-450 reductase. Also all six of the brain tumors investigated could metabolize tirapazamine to the two-electron reduction product. CONCLUSION: These findings would favor primary brain tumors as suitable targets for bioreductive therapy. PMID- 8005795 TI - Increase in tumor blood flow by pentoxifylline. AB - PURPOSE: The effect of pentoxifylline (PTX) on the blood flow in experimental rodent tumors was investigated. METHODS AND MATERIALS: When the R3230 AC adenocarcinoma implanted in the leg of Fischer 344 rats grew to about 1 g, the effect of PTX on the blood flow in the tumor and in the skin and muscle was determined with the microsphere method using 85Sr labelled 25 microns diameter microspheres. The SCK mammary carcinoma was induced subcutaneously in the leg or foot of A/J mice and the effect of PTX on the tumors was investigated: the blood perfusion in the leg tumors (7 mm in diameter) was determined with the 86Rb uptake method and that in the foot tumors (5 mm diameter) was determined with the laser Doppler flow (LDF) method. RESULTS: The blood flow in the R3230 AC adenocarcinoma significantly increased when measured 30 min after an IP injection of 50 mg/kg PTX while the blood flow in the normal skin and muscle remained unchanged. The 86Rb uptake in the SCK tumor slightly increased 30 min after an IP injection of 50 mg/kg PTX. The LDF in the SCK tumors grown in the foot began to increase 5-10 min after an injection of 25 mg/kg PTX reaching 1.5-2.0 times in 20 30 min and it returned to the original level at 60 min. CONCLUSION: The results in the present study together with our previous observation that PTX increases the tumor pO2 in rodent tumors strongly suggest that PTX may be useful for increasing the radiosensitivity of human tumors. PMID- 8005796 TI - Relationship between radiobiological hypoxia in tumors and electrode measurements of tumor oxygenation. AB - PURPOSE: To determine whether electrode measurements of tumor oxygenation, made in a variety of murine tumor models, correlate with estimates of radiobiological hypoxia in the same tumor systems. METHODS AND MATERIALS: The tumor models used were a C3H mammary carcinoma grown in the feet of CDF1 mice; the SCCVII, KHT and RIF-1 tumors grown in the feet or flanks of C3H/Km mice; and the CaNT and SaF tumors grown on the backs of CBA mice. All treatments were performed when tumors were about 200 mm3 in size. Radiobiological hypoxic fractions were determined using either a paired survival curve assay, with survival measured 0-24 h after irradiation, or using a clamped tumor control assay, with percent local tumor control estimated 90 days after treatment. Measurements of tumor oxygen partial pressure (pO2) distributions were performed using Eppendorf oxygen electrodes. RESULTS: The hypoxic fractions determined from the radiation response data were about 1% in RIF-1 and SCCVII, 12% in C3H and KHT, 28% in CaNT and up to 38% in SaF tumors. When this data was compared with the tumor oxygenation measurements it was found that as hypoxic fraction increased the mean, median, and the percentage of pO2 values < or = 5 mmHg showed a trend towards poorer oxygenation status. However, none of these pO2 changes were significantly correlated with hypoxia. Moreover, the pO2 values < or = 2.5 mmHg indicated an improvement in oxygen status with increasing hypoxic fraction. CONCLUSION: Electrode measurements of tumor oxygenation alone may, therefore, not be a good indicator of tumor hypoxia across different tumor cell lines. PMID- 8005797 TI - Effect of carbon monoxide breathing on hypoxia and radiation response in the SCCVII tumor in vivo. AB - PURPOSE: To study the influence of a clinically relevant concentration of carbon monoxide (CO) on tumor oxygenation and response to irradiation. METHODS AND MATERIALS: The murine tumor model was the SCCVII squamous cell carcinoma transplanted to the feet of C3H/Km mice. RESULTS: Sixty minutes of breathing CO at 200 ppm resulted in a carboxyhemoglobin level of 15%. This resulted in a reduction in p50 (the oxygen partial pressure at which hemoglobin is 50% saturated) to 78% of the control value, and a decrease in tumor blood perfusion to 73% of the control value. The combined effect of a decrease in effective hemoglobin and blood perfusion resulted in a reduction in tumor oxygen supply to 62% of the control value. In agreement with this, intratumoral pO2 measurements showed a significant increase in tumor hypoxia, such that the percentage of measurements with low pO2 (< or = 5 mmHg) increased from 33% to 62%. The fraction of clonogenic hypoxic cells, measured radiobiologically by paired cell survival curves, similarly increased from 0.2% to 3.8%. Radiation sensitivity, evaluated from in vivo-in vitro excision assay, was significantly decreased by CO breathing with both single dose and fractionated irradiation. The observed enhancement ratios for radiation given in 1, 4, 8, and 12 fractions were 0.71, 0.77, 0.83, and 0.71, respectively. CONCLUSION: The present SCCVII tumor data confirm the general experimental observation that CO breathing significantly increases tumor hypoxia and reduces the effectiveness of ionizing irradiation. PMID- 8005798 TI - Importance of nicotinamide dose on blood pressure changes in mice and humans. AB - PURPOSE: The importance of nicotinamide dose on inducing blood pressure changes in mice and humans was investigated. METHODS AND MATERIALS: Blood pressure measurements in human volunteers were made using an inflated cuff procedure after oral ingestion of 3 or 6 g nicotinamide. Animal blood pressure measurements were performed in fully awake nonanesthetized female CDF1 mice, 24 h after cannulation of the carotid artery. RESULTS: In humans, the average (+/- 1 SE) resting systolic and diastolic pressures were 122.8 mmHg (+/- 2.5) and 80.6 mmHg (+/- 2.1), respectively. They were unchanged during the first 3 h after ingestion of either 3 g or 6 g nicotinamide. The resting value (+/- 1 SE) in mice was 115.1 mmHg (+/- 4.0) and this was significantly reduced following intraperitoneal injection of 400-1000 mg/kg nicotinamide. This decrease was maximal within 15-30 min after injection and was linearly dependent on drug dose. At doses of 200 mg/kg or less, no significant effect on blood pressure was observed. CONCLUSION: Doses between 100-200 mg/kg in mice are known to be equivalent to 6 g in man and can also produce maximal radiosensitization in murine tumors. Our results, therefore, not only show that the mouse and human data are entirely consistent, but also suggest that nicotinamide-induced decreases in blood pressure are not necessary for radiosensitization. PMID- 8005799 TI - Micro-regional mapping of HbO2 saturations and blood flow following nicotinamide administration. AB - PURPOSE: Although nicotinamide administration has increased the radiosensitivity of experimental tumors, there is a scarcity of data detailing the underlying physiological mechanisms. The current study presents a method for quantifying both microregional distributions of intravascular HbO2 saturations and the presence or absence of blood flow in adjacent frozen tumor sections. METHODS AND MATERIALS: Two murine tumor cell lines, KHT and SCCVII, were implanted and quick frozen without the use of anesthetics. Nicotinamide was administered IP 1 h prior to freezing, and a fluorescent dye that preferentially stains cells adjacent to blood vessels was injected i.v. 1 min prior to freezing. To visualize the presence or absence of blood flow, six micron sections were first cut using a cryostat. The remaining frozen tumor block was then analyzed cryospectrophotometrically to determine intravascular HbO2 levels. RESULTS: While KHT HbO2 levels increased somewhat predictably following nicotinamide, the response in SCCVII tumors varied with distance from the tumor surface. Near the periphery, SCCVII HbO2 levels increased, but nearer the tumor center, HbO2 levels actually decreased. Perfused blood vessels were uniformly distributed throughout the tumor volume except in regions of necrosis. Even vessels containing no measurable oxygen remained perfused, as evidenced by the presence of the fluorescent marker. CONCLUSION: These results demonstrate that nicotinamide raises intravascular HbO2 saturations in both KHT and SCCVII tumors. This increase in oxygen delivery is not evenly distributed throughout the tumor volume in spite of a uniform distribution of perfused blood vessels. Blood flow in a substantial proportion of these vessels is most likely not sufficiently rapid to serve a functional purpose in terms of oxygen supply to the surrounding tumor tissue. PMID- 8005800 TI - Combination of photodynamic therapy (PDT) and melphalan in experimental tumors. AB - PURPOSE: To investigate whether application of "early" photodynamic therapy (PDT) using a disulphonated aluminium phthallocyanine photosensitizer can potentiate the action of melphalan in experimental RIF-1 tumors in vivo. METHODS AND MATERIALS: Tumors were irradiated with laser light of wavelength 675 nm 60 min after treatment with the photosensitizer and 15 min after melphalan. Melphalan pharmacokinetics were measured using high performance liquid chromatography with optical detection. RESULTS: Melphalan and PDT when given alone, caused a significant delay in tumor growth. This was increased for the combined treatment. Pharmacokinetic analyses showed that levels of free, unreacted melphalan in freely circulating blood are unaffected by combined treatment. However, significant differences in tumor levels were observed between treatment with melphalan alone or in combination. Whereas in the former, melphalan is still present in tumors after 2 h, it was not detectable even at the earliest time of 15-23 min for the combined treatment. CONCLUSION: The antitumor effects were additive with no evidence of significant potentiation. PMID- 8005801 TI - The influence of microenvironment on the cytotoxicity of TNF [symbol: see text] vitro. AB - PURPOSE: Investigations were undertaken to study the influence of oxygen levels on tumor necrosis factor [symbol: see text] (TNF [symbol: see text] toxicity in vitro. METHODS AND MATERIALS: The cell line used to assess the cytotoxicity of TNF [symbol: see text] the mouse fibroblast line L929. The cell line was incubated under conditions of 21%, 10%, 5% and 2% oxygen either before or during exposure to TNF [symbol: see text]. All incubations with TNF were for 24 h in the presence of 1 microgram/ml actinomycin D. Cell number was assessed immediately following treatment by a colormetric method. RESULTS: By preincubating L929 cells under various oxygen conditions for 24 h prior to incubating with TNF [symbol: see text], we show that pretreatment does influence TNF [symbol: see text] cytotoxicity since up to 50 times more TNF [symbol: see text] is required to elicit the same survival level when L929 cells have been preincubated for 24 h at oxygen levels relevant to those in solid tumors, that is 2% rather than at 21%. A 24 h preincubation under an environment of 5% oxygen is not as effective at inducing resistance to TNF [symbol: see text] as incubation under 2% oxygen. However, this resistance could be significantly enhanced by lengthening the preincubation time. Indeed cells cultured for five passages under 5% oxygen levels are approximately 50 times more resistant to TNF [symbol: see text] than cells cultured under 21% oxygen. The resistance induced by conditions of reduced oxygen tension could be reversed over a 24 h period if cells were returned to an environment containing of reduced oxygen tension could be reversed over a 24 h period if cells were returned to an environment containing 21% oxygen. CONCLUSION: The oxygen content of the cellular microenvironment has a profound influence on the cytotoxic action of TNF. PMID- 8005802 TI - Comparison of the effects of hydralazine on tumor and normal tissue blood perfusion by MRI. AB - PURPOSE: The differential effects on blood perfusion of the vasodilator hydralazine (HYD) between tumor and normal muscle have been measured using the dynamic enhanced-magnetic resonance imaging (DE-MRI) technique. METHODS AND MATERIALS: DE-MRI is a noninvasive method of determining blood perfusion in tumors and normal tissues using the MR contrast agent Gd-DTPA. Hydralazine is currently being used in an attempt to increase tumor response to bioreductive agents and to hyperthermia. RESULTS: We show that a dose of 1.2 mg/kg HYD causes an increase in tumor perfusion while doses > or = 2.5 mg/kg cause a decrease in tumor perfusion. The latter was accompanied by a dose-dependent increase in normal muscle perfusion consistent with the "steal effect." CONCLUSION: This study demonstrates the sensitivity of the DE-MRI technique and its capability of providing estimates of blood perfusion in normal and tumor tissue as well as in smaller regions of a solid tumor. Such features would make it clinically useful in the study of tumor response to radiation therapy and chemotherapy in patients. PMID- 8005803 TI - Modulation of tumor hypoxia by conventional chemotherapeutic agents. AB - PURPOSE: We have evaluated the capacity of a number of common cancer chemotherapeutic drugs to modulate the oxygenation of human tumor xenografts growing in murine hosts. METHODS AND MATERIALS: Considerable effort has been expended on developing methods to radiosensitize hypoxic cells, or to selectively kill them with appropriate chemicals. Another approach, suggested by our ongoing studies with spheroids in vitro, is to modify tumor oxygenation by physiological means. The feasibility of this approach is illustrated in this article using human tumor xenografts in mice treated with doxorubicin or mitomycin C plus radiation. The therapeutic potential of the combination treatments has been assessed using fluorescence-activated cell sorting techniques to isolate and differentially study hypoxic vs. aerobic cell subpopulations from the xenografts. Additionally, drug-induced changes in blood flow have been quantified at the macroscopic level with laser Doppler flowmetry, and at the microregional level with image analysis techniques. RESULTS: At doses which produced only modest amounts of tumor cell killing, doxorubicin and mitomycin C markedly altered tumor blood flow in all tumor types examined, and with all assays used. CONCLUSION: Common anti-cancer agents may find new use as blood flow modifiers for combined modality treatments, in addition to their conventional use as "pure" cytotoxins. PMID- 8005804 TI - Hypoxic fractions measured in murine tumors and normal tissues using the comet assay. AB - PURPOSE: To apply the alkaline comet assay to the detection of radiobiologically hypoxic cells in solid tumors and normal tissues of mice, and to examine the influence of strand break repair on the oxygen enhancement ratio measured using the alkaline comet assay. METHODS AND MATERIALS: In previous studies, we found that hypoxic fraction in squamous cell carcinomas growing in C3H mice could be reliably and easily measured using the alkaline comet assay. The comet assay applies fluorescence microscopy and image analysis to examine patterns of migration of deoxyribonucleic acid from individual cells embedded in agarose and exposed to an electric field. This method has sufficient resolution to detect subpopulations of hypoxic cells which show about 3 x fewer strand breaks than aerobic cells after irradiation. RESULTS: Fast rejoining kinetics in vitro are comparable to those measured in vivo, and rejoining of strand breaks in hypoxic tumor cells occurs at a similar rate as rejoining in aerobic cells. Little residual damage was detectable using the comet assay in tumors 4-24 h following 15 Gy, allowing repeat measurements to be performed. Bone marrow and testis, but not liver, spleen, or jejunum contained a small fraction of hypoxic cells when mice breathed 10% oxygen during irradiation. CONCLUSION: The comet assay confirms that some normal tissues may border on hypoxia. Rejoining of strand breaks occurs rapidly in both oxic and hypoxic cells so that the oxygen enhancement ratio remains relatively constant with time after irradiation. Interestingly, a smaller oxygen enhancement ratio was observed in tumors than was expected, probably as a result of the presence of acutely hypoxic cells. PMID- 8005806 TI - Ischaemia induced cell death in tumors: importance of temperature and pH. AB - PURPOSE: Increasing attention has focussed on the therapeutic potential of agents which can reduce tumor blood flow and induce ischaemia for long enough to result in tumor cell death. A confounding factor in this approach is the fact that the core temperature of superficial tumors reduces when the supplying blood flow is occluded and therefore protects the tumor cells from "metabolic" death. Consequently, we have tested the importance of tumor temperature on the relationship between vascular occlusion and cell death. METHODS AND MATERIALS: The murine tumor CaNT used in this study was implanted subcutaneously in the dorsum. Total vascular occlusion was achieved by physically occluding the blood supply to the tumors for periods between 1 and 20 h. The mouse temperature was controlled by placing the whole body in a thermostatically controlled incubator maintained at 35 degrees C. Tumor cell survival was assessed using an excision assay and by measuring the delay in growth of treated tumors. Measurement of tumor pH was achieved using microelectrodes. RESULTS: The core temperature of unclamped tumors was approximately 33 degrees C, but fell by about 5 degrees C during vascular occlusion at room temperature. Tumor cell survival was decreased with increasing periods of vascular occlusion at room temperature, but a greater reduction in cell survival and correspondingly increased regrowth delay was observed when the tumor temperature was prevented from cooling below preocclusion values. The extracellular pH (pHe) fell during vascular occlusion and this reduction was greater when the tumor temperature was maintained at preocclusion values. This extracellular acidosis is expected to partly explain the observation of greater tumor cell death in those tumors whose temperature does not reduce during occlusion. CONCLUSION: The temperature of superficial tumors reduces in response to vascular occlusion. This may result in an underestimation of the cytotoxicity of agents which reduce tumor blood flow as the tumor cooling protects the cells from the acidosis that accumulates within the occluded tumor. PMID- 8005805 TI - Reoxygenation and rehypoxiation in the SCCVII mouse tumor. AB - PURPOSE: To test the hypothesis that, following preferential killing of tumor hypoxic cells, the fraction of hypoxic cells in the tumor will reestablish itself to pretreatment levels (rehypoxiation) with the same kinetics as for reoxygenation. METHODS AND MATERIALS: Mouse squamous cell carcinoma VII (SCCVII) tumors were treated with a single dose of 10 Gy or a single dose of the bioreductive hypoxic cell cytotoxin, tirapazamine (SR 4233, 0.2 mmol/kg), which preferentially kills hypoxic cells within the tumor. Hypoxic fractions were determined by the paired survival curve technique using the in vivo-in vitro clonogenic assay 0-24 h after treatment. RESULTS: Immediately after irradiation with 10 Gy, the hypoxic fraction of the tumors increased to 80% and rapidly returned to pretreatment levels 3-6 h later. Within 1 h of injecting tirapazamine, the hypoxic fraction fell to 0.57% (about 7% of pretreatment levels) and returned to pretreatment levels 3-5 h later. CONCLUSION: The return to pretreatment levels of hypoxia among tumor cells surviving a single dose of radiation (reoxygenation) and of the hypoxic cell toxin tirapazamine (rehypoxiation) was rapid and occurred with similar kinetics for the two processes. These data support the hypothesis that reoxygenation and rehypoxiation are different manifestations of the same phenomenon and result from fluctuating tumor blood flow which creates acute hypoxia. PMID- 8005807 TI - Hydralazine at thermoradiotherapy: tumor size and blood flow effects. AB - PURPOSE: This study was aimed to assess the dependence on tumor size and blood flow of the efficacy of a vasoactive drug hydralazine with thermoradiotherapy. METHODS AND MATERIALS: Experiments were performed on mice bearing SCC-VII tumors with volumes of about 85 and 340 mm3 (7-8 or 11-12 days after transplantation, respectively). Local hyperthermia (water bath, 43 degrees C, 0.5 h) was started 3 h after irradiation of tumors. Hydralazine (2.5 mg/kg, IP) was given 0.5 h before heating. Tumor blood flow was evaluated by laser Doppler flowmetry before, during and up to 2 days after the treatments. RESULTS: It was shown that hydralazine and hyperthermia, even in combination with each other, had very weak anti-tumor effect, especially for 85 mm tumors. The agents also insignificantly enhanced the efficacy of radiotherapy excluding the case of polyradiomodification for 340 mm3 tumors when a dose modifying factor of about 2.0 was achieved. Thermometry showed only a small improvement by HDZ in heating patterns of tumors of both sizes. Meanwhile, the therapeutic efficacy of hydralazine and heat was correlated with the changes in tumor blood flow, first of all with the delayed effects. The radiomodifiers induced only minor and transient suppression of perfusion in the smaller tumors, and more markedly and for longer time decreased blood flow in the larger tumors. In the latter case, the inhibiting effect of the drug plus hyperthermia remained for at least 48 h after the treatment. CONCLUSION: (a) The combined use of hydralazine and heat seems to be advisable only at radiotherapy of rather large advanced tumors; (b) the efficacy of such radiomodification is correlated with prolonged inhibition of tumor blood flow by these agents; and (c) hydralazine and hyperthermia are likely to kill selectively both acutely and chronically hypoxic radioresistant cancer cells. PMID- 8005808 TI - Thermosensitization and modification of cytosolic calcium concentration by verapamil and diltiazem in mouse mammary carcinoma cells. AB - PURPOSE: The cardinal role of Ca2+ signaling in the development of heat damage at 42 degrees C and 44 degrees C and the effect of verapamil and diltiazem on the change of cytosolic Ca2+ concentration, [Ca2+]c, were investigated. METHODS AND MATERIALS: Hyperthermic treatment was performed by immersing the tubes containing the mouse mammary carcinoma FM3A cells in a water-bath set at 42.0 degrees C or 44.0 degrees C. The [Ca2+]c of a single cell after hyperthermia was monitored by a digital image analyzing technique using Fura-2. Influx of Ca2+ was examined by the measurement of the radioactivity of 45Ca2+ incorporated into the cells for 60 min during or after hyperthermia. RESULTS: While the [Ca2+]c of the cells treated at 37 degrees C for 60 min was less than 230 nM, the percentage of the cells showing more than 230 nM increased after 42 degrees C hyperthermia and that of the cells showing more than 300 nM increased after 44 degrees C hyperthermia. When cellular uptake of 45Ca2+ during and after hyperthermia was examined, the increase in 45Ca2+ uptake was observed only for 44 degrees C hyperthermia. Verapamil or diltiazem (100 microM) enhanced a delay of cell growth, an increase in [Ca2+]c and an increase in 45Ca2+ influx for 42 degrees C and 44 degrees C hyperthermia. CONCLUSION: These results are compatible with the view that the increase in [Ca2+]c after 42 degrees C hyperthermia results from intracellular release from calcium store sites whereas the rise in [Ca2+]c after 44 degrees C hyperthermia is mainly due to entry of extracellular Ca2+. Verapamil or diltiazem combined with hyperthermia increased [Ca2+]c, which may play a cardinal role in thermosensitization by these agents. PMID- 8005809 TI - Dependence of 5-fluorouracil-mediated radiosensitization on DNA-directed effects. AB - PURPOSE: Although 5-fluorouracil (FUra) has been demonstrated to be a radiation sensitizer both in the laboratory and the clinic, it is not known whether radiosensitization results primarily from FUra's DNA or RNA-directed effects. METHODS AND MATERIALS: We studied the radiosensitizing effects of FUra +/- thymidine (dThd)) on HT29 human colon cancer cells, which are relatively sensitive to the DNA-directed action of FUra, in comparison to SW620 and HuTu80 human colon cancer cells, which are relatively resistant to FUra's DNA-directed effects. We hypothesized that if FUra were acting chiefly through DNA dependent mechanisms, HT29 cells would (a) show greater radiosensitization than SW620 and HuTu80 cells under the same conditions of exposure; and (b) demonstrate selective reversal of radiation sensitivity (compared to cytotoxicity) in the presence of FUra + dThd, compared to FUra alone. RESULTS: We found that the enhancement ratio produced by a 24 h exposure to 10 microM FUra was significantly greater in HT29 cells compared to SW620 and HuTu80 cells (enhancement ratios of 2.1 +/- 0.1; 1.1 +/- 0.1, and 1.3 +/- 0.1, respectively). Furthermore, in HT29 cells, dThd blocked FUra-mediated radiosensitization to a greater extent than FUra-mediated cytotoxicity. Thus, our hypotheses were confirmed. CONCLUSION: These findings support the concept that the manipulation of FUra's DNA-dependent actions, for example, through modulators of thymidylate synthase (TS) activity, may increase radiosensitization in clinical trials in the treatment of gastrointestinal cancers. However, since resistance to the DNA-directed effects of fluoropyrimidines can result from mechanisms unrelated to TS inhibition, additional strategies will be required to potentiate fluoropyrimidine-mediated radiosensitization. PMID- 8005810 TI - Additive effects of cepharanthin in CDDP/hyperthermia combination therapy against transplantable human esophageal cancer in nude mice. AB - PURPOSE: Additive effects of cepharanthin in CDDP/hyperthermia combination therapy were evaluated. METHODS AND MATERIALS: Nude mice bearing a transplantable human esophageal cancer (ES0-2), classified histologically as a moderately differentiated squamous cell carcinoma, were treated with cepharanthin (20 mg/kg IP) in addition to cis-diamminedichloroplatinum(II) (CDDP; 4 mg/kg IP) and/or hyperthermia at 42 degrees C for 30 min, to determine the additive effects of cepharanthin. Furthermore, effects of cepharanthin on intratumoral concentration of CDDP were evaluated. RESULTS: Cepharanthin itself did not have an anti-tumor effect. This agent did not enhance the anti-tumor effect of CDDP alone, but enhanced the anti-tumor effects of both 42 degrees C hyperthermia alone, and combination therapy with CDDP and 42 degrees C hyperthermia. The concentration of CDDP in the tumors treated by 42 degrees C hyperthermia was slightly higher than in nonheated tumors. Cepharanthin did not affect the intratumoral concentration of CDDP, irrespective of whether hyperthermia was applied. CONCLUSION: Cepharanthin enhanced the effect of CDDP/hyperthermia combination therapy through thermoenhancing effect. PMID- 8005811 TI - A feasibility study of 252Cf neutron brachytherapy, cisplatin + 5-FU chemo adjuvant and accelerated hyperfractionated radiotherapy for advanced cervical cancer. AB - PURPOSE: To evaluate the feasibility and toxicity of 252Cf neutron brachytherapy combined with hyperaccelerated chemoradiotherapy for Stage III and IV cervical cancers. METHODS AND MATERIALS: Eleven patients with advanced Stage IIIB-IVA cervical cancers were treated with 252Cf neutron brachytherapy in an up-front schedule followed by cisplatin (CDDP; 50 mg/m2) chemotherapy and hyperfractionated accelerated (1.2 Gy bid) radiotherapy given concurrently with intravenous infusion of 5-Fluorouracil (5-FU) (1000 mg/m2/day x 4 days) in weeks 1 and 4 with conventional radiation (weeks 2, 3, 5, and 6). Total dose at a paracervical point A isodose surface was 80-85 Gy-eq by external and intracavitary therapy and 60 Gy at the pelvic sidewalls. RESULTS: Patients tolerated the protocol well. There was 91% compliance with the chemotherapy and full compliance with the 252Cf brachytherapy and the external beam radiotherapy. There were no problems with acute chemo or radiation toxicity. One patient developed a rectovaginal fistula (Grade 3-4 RTOG criteria) but no other patients developed significant late cystitis, proctitis or enteritis. There was complete response (CR) observed in all cases. With mean follow-up to 26 months, local control has been achieved with 90% actuarial 3-year survival with no evidence of disease (NED). CONCLUSION: 252Cf neutrons can be combined with cisplatin and 5-FU infusion chemotherapy plus hyperaccelerated chemoradiotherapy without unusual side effects or toxicity and with a high local response and tumor control rate. Further study of 252Cf neutron-chemoradiotherapy for advanced and bulky cervical cancer are indicated. We found chemotherapy was more effective with the improved local tumor control. PMID- 8005813 TI - Use of the hypoxic cell sensitizer etanidazole (SR-2508) with intravenous melphalan and prednisone in the treatment of multiple myeloma: a pharmacokinetic study. AB - PURPOSE: A study was undertaken adding the alkylating agent sensitizer etanidazole to intravenous melphalan and oral prednisone for patients with multiple myeloma. This study explored the toxicity profile of these agents when given together and assessed the ability to attain adequate serum levels of etanidazole to permit sensitization to occur. METHODS AND MATERIALS: Etanidazole was administered intravenously in two doses of 3 g/m2 and 5 g/m2 90 min apart immediately prior to the administration of intravenous melphalan and oral prednisone for three consecutive cycles (total dose 24 g/m2). Patients received three additional cycles without etanidazole, allowing a comparison of hematologic toxicity from melphalan with and without etanidazole. RESULTS: Hematologic toxicity was moderate (Grade 3 or 4), but severity was similar during cycles with and without etanidazole. Only one patient developed a Grade 1 peripheral neuropathy questionably related to etanidazole. Most patients had etanidazole levels of > or = 70 ug/ml for 7 h, a level felt to be necessary for sensitization to occur. CONCLUSION: Etanidazole, administered as described, results in adequate serum levels for potential alkylating agent sensitization, without significant toxicity. PMID- 8005812 TI - Combined-modality therapy of esophageal cancer with radiotherapy, etanidazole, and cisplatin-fluorouracil, with or without surgery: neurotoxicity, other toxicities and outcome. AB - PURPOSE: To investigate whether etanidazole and cisplatin can be given safely together and to evaluate the relationship between incidence of peripheral neuropathy and cumulative exposure to etanidazole and cisplatin, as well as other toxicities and treatment outcome. METHODS AND MATERIALS: Thirty-two previously untreated patients with locally advanced esophageal cancer were entered on a Phase I study of etanidazole combined with radiation therapy and chemotherapy. Cisplatin/5-FU (two cycles, weeks 1 and 4) and etanidazole (weeks 2, 3 and 5) were given concurrently with radiation therapy. Eligible patients then underwent surgical resection. All patients were scheduled to receive two additional cycles of cisplatin/5-FU chemotherapy after completion of radiation therapy (definitive arm) or surgery (preoperative arm). RESULTS: Of 19 fully evaluable patients, nine (47%) developed peripheral neuropathy. Six of six patients, 65 years or older, experienced peripheral neuropathy, compared with three of 13 patients less than 65 years old (p = .003). For patients younger than 65 years, two of the two patients with single dose area under the curve (AUC) > 4.0 mMhr experienced peripheral neuropathy, compared with one of 11 patients with single-dose AUC < 4.0 mMhr (p = .03). Grade 4 toxicity included neutropenia (23%) and thrombocytopenia (26%). No other Grade 4 toxicity was observed. The pathologic complete response rate in patients who underwent surgical resection was 29%. CONCLUSION: This regime of chemotherapy, radiotherapy, and etanidazole had acceptable toxicity. However, combining etanidazole and cisplatin appears to increase the risk of developing peripheral neuropathy for at least some categories of patients. Further studies of these interactions are needed. PMID- 8005814 TI - Phase I pharmacokinetic study of the hypoxic cell sensitizer etanidazole with carboplatin and cyclophosphamide in the treatment of advanced ovarian cancer. AB - PURPOSE: A Phase I study was undertaken to determine the maximum tolerated dose of the hypoxic cell sensitizer etanidazole which could be administered with carboplatin and cyclophosphamide, to determine whether adequate serum levels of etanidazole were achieved to allow for alkylating agent sensitization, and whether pretreatment with etanidazole altered carboplatin pharmacokinetics. METHODS AND MATERIALS: Patients received 2 g/m2 of intravenous etanidazole followed by a second dose of 4 g/m2 90 min later, followed by intravenous carboplatin (300 mg/m2) and cyclophosphamide (600 mg/m2) for four treatment cycles. Patients received an additional two cycles of carboplatin and cyclophosphamide without etanidazole. RESULTS: Two patients who received a total of 24 g/m2 of etanidazole developed Grade 1 neurotoxicity, and therefore etanidazole doses were not escalated further. The grade of granulocytopenia was worse after cycles with etanidazole than after those without (p = 0.03), but clinical outcome was not different. Etanidazole levels were adequate for alkylating agent sensitization (> 70 ug/ml) in all patients for the majority of the 7 h of testing. Pharmacokinetic data suggested t1/2 alpha and t1/2 beta for carboplatin were prolonged after pretreatment with etanidazole. CONCLUSION: Etanidazole, 2 g/m2 followed by 4 g/m2 90 min later, is safe and results in adequate serum levels for alkylating agent sensitization. Neurotoxicity appears to prevent dose escalation of etanidazole, and an interaction between etanidazole and carboplatin may have enhanced neurotoxicity in these patients. PMID- 8005815 TI - Clinical and biological studies of estramustine phosphate as a novel radiation sensitizer. AB - PURPOSE: Estramustine phosphate (EMP), a nor-nitrogen mustard carbamate derivative of estradiol-17 beta-phosphate, causes G2/M phase arrest in treated cells through its specific binding to microtubule associated proteins. Since cells in the G2/M phase are the most radiosensitive, cell culture experiments were performed to determine whether EMP would enhance the radiosensitivity of related human tumor cells. Based on the cell culture findings and well known pharmacokinetic data in humans, a Phase II prospective study of concomitant radiotherapy (RT) and EMP plus Velban for locally advanced carcinoma of the prostate was carried out. METHODS AND MATERIALS: Three established human tumor cells, DU-145 cells (prostate), MCF-7 cells (breast), and U-251 cells (malignant glioma), were used to determine cell survival curves with and without the drug. Flow cytometry was used to obtain the cell cycle distribution of cells that were exposed to the drug for periods of 1 day to 1 week. Patients with locally advanced prostate cancer (Stages B2, C, D1) were entered into the Phase II study. All patients received a total tumor dose of 65-70 Gy over 7 weeks. Oral EMP was administered daily and Velban was administered weekly, concomitantly during the course of RT. RESULTS: Radiosensitization was dependent on the exposure time and the drug concentration prior to radiation. No radiosensitization was obtained when cells were exposed to the drug after irradiation. The enhancement ratios varied from 1.3-1.6 at the 10% survival level. All patients who received the combined RT and EMP plus Velban achieved complete response (n = 27). The rate of PSA (prostate specific antigen) reduction was very prompt compared to that of the RT alone group. There was not disproportionately enhanced side effects for the combined regimen. CONCLUSION: EMP enhances radiation induced cytotoxicity in several human tumor cells in culture. The effect is most significant after prolonged exposure to the drug before irradiation. Documented G2/M phase cell cycle block by EMP is the likely mechanism of radiosensitization. The preliminary clinical findings with the combined RT and drugs are highly encouraging. PMID- 8005816 TI - Metabolic studies and neurotoxicity in tumors and brain of mice after hypoxic cell sensitizers. AB - PURPOSE: The effects of the radiosensitizers RK-28 and RP-170, both 2 nitroimidazole nucleoside analogues, and KU-2285, a fluorinated 2-nitroimidazole, as well as etanidazole (ETA) on glucose metabolism in mouse tumors and brain were studied to assess their degree of neurotoxicity. METHODS AND MATERIALS: Adult male C57Bl mice received differing doses of the above sensitizers IP. Blood, brain, and tumor samples were removed at various times and the levels of glycolytic metabolites determined. Glucose uptake and phosphorylation in brain was measured by the 2-deoxyglucose method of Sokoloff et al. (6). RESULTS: RP-170 showed neither signs of toxicity nor significant alterations in glucose metabolism in brain or tumor at doses up to 4 g/kg b.w. up to 4 h. By contrast, RK-28 was extremely neurotoxic at a dose of 1 g/kg b.w. with a high degree of lethality, resulting in a highly significant increase in the brain glucose level from 0.38 mumol/g to 2.20 mumol/g (p < 0.001) 2 h after administration, whereas that in the tumor was decreased. KU-2285 and ETA were significantly (p < 0.01) less toxic than RK-28 at this dose, as reflected in a lower increase in the brain glucose level (0.60 mumol/g), although KU-2285 approached that of RK-28 (1.43 mumol/g; p < 0.01) after 2 h following a dose of 2 g/kg b.w. However, in contrast to the other sensitizers, KU-2285 concomitantly also resulted in a highly significant continuous increase (p < 0.01) in tumor glucose levels. Labeled 3H-2 deoxyglucose studies showed that RP-170 neither markedly affected the uptake of total radioactivity into the brain nor its degree of phosphorylation whereas, KU 2285 (2 g/kg) and RK-28 (1 g/kg) decreased uptake by approximately 50% and phosphorylation approximately 3 and 4-fold, respectively. At doses of 1 g/kg, ETA and KU-2285 showed no significant changes in these parameters. This indicates a decreased level of neurotoxicity. CONCLUSION: Since the adult brain relies solely on glucose metabolism for its energy supply, interference to this pathway may be instrumental in the development of neurotoxicity, thus, underlining the need for such metabolic studies to assess the level of toxicity by radiosensitizers. PMID- 8005817 TI - Inhibitors of poly (ADP-ribose) synthesis inhibit the two types of repair of potentially lethal damage. AB - PURPOSE: The purpose of this study was to examine whether 3-amino-benzamide (3ABA), an inhibitor of poly (ADP-ribose) synthesis, inhibits the two types of potentially lethal damage (PLD) repair, termed slow and fast. METHODS AND MATERIALS: The fast-type PLD repair was measured by the decrease in survival of V79 Chinese hamster cells by postirradiation treatment with 3ABA. The slow-type PLD repair was measured by the increase in survival by posttreatment with conditioned medium (CM), which became conditioned by growing a crowed culture of cells and supports the slow-type PLD repair. RESULTS: Up to 1 mM, 3-ABA inhibited the slow type repair; at doses of 2 mM and above, it inhibited the fast type of PLD repair. CONCLUSION: There are quantitative differences in cellular effects of 3ABA dependent on concentration. Poly (ADP-ribose) appears to play an important role in the PLD repairs and has little effect on the repair of sublethal damages. PMID- 8005818 TI - Fluorinated 2-nitroimidazole derivative hypoxic cell radiosensitizers: radiosensitizing activities and pharmacokinetics. AB - PURPOSE: To assess the effects of incorporation of a CF2 group into the side chain of a 2-nitroimidazole derivative, we evaluated the in vitro and in vivo radiosensitizing activities of KU-2285 (a 2-nitroimidazole derivative with an N1 substituent of -CH2CF2CONH(CH2)nOH, n = 2) and its related compounds in comparison with those of comparable nonfluorinated compounds. The pharmacokinetics of these compounds in murine tumors was also tested. METHODS AND MATERIALS: KU-2285, KU-3202 (n = 3) and KU-3207 (n = 4) are fluorinated 2 nitroimidazole derivative compounds with similar structures. Etanidazole (a 2 nitroimidazole derivative with an N1-substituent of -CH2CONH(CH2)nOH, n = 2) and its related compounds, KU-3205 (n = 3) and KU-3206 (n = 4) were also tested. The in vitro radiosensitizing activities of each compound for hypoxic cells was evaluated with a standard colony formation method. The in vivo radiosensitizing activities of these compounds were tested in female C3H/He mice bearing SCCVII tumors using an in vivo/in vitro clonogenic assay. The pharmacokinetic studies were performed in C3H/He mice bearing the SCCVII tumor. Samples were analyzed by reverse-phase high-performance liquid chromatography. RESULTS: The in vitro radiosensitizing activities of fluorinated 2-nitroimidazoles were higher than those of the nonfluorinated compounds. Although the in vivo radiosensitizing activity of KU-2285 was higher than that of etanidazole (p < 0.05), other fluorinated 2-nitroimidazoles showed less radiosensitizing activity than the comparable nonfluorinated compounds. The compound was eliminated from serum more rapidly with the increase in the number of CH2 group in the side chain of the compound in each series. CONCLUSION: Although the in vitro sensitizing activity of the fluorinated compounds was higher than that of the comparable nonfluorinated compounds, the in vivo radiosensitizing activity of all fluorinated compounds but KU-2285 was lower than that of comparable etanidazole group compounds, probably due to their lower molecular concentrations in tumor and rapid elimination. PMID- 8005819 TI - Reoxygenation in the SCCVII tumor after KU-2285 sensitization plus single or fractionated irradiation. AB - PURPOSE: Because reoxygenation of solid tumors after irradiation with a hypoxic cell sensitizer has never previously been investigated, we assessed the reoxygenation in SCCVII tumors after treatment with KU-2285 plus single or fractionated irradiation. METHODS AND MATERIALS: KU-2285 (100 mg/kg) was injected intraperitoneally into C3H mice bearing 1-cm SCCVII tumors at 30 min before a single dose of 12 Gy or three fractions of 5 Gy at 12 h intervals. Changes of the hypoxic fraction (HF) were then evaluated by the paired survival curve method. RESULTS: Since the radiosensitizing effect of KU-2285 was relatively persistent, the HF was only evaluable after 6 h of irradiation. The HF of untreated SCCVII tumors was 9.1%. After treatment with KU-2285 and 12 Gy, the HF was 25% at 6 h, 32% at 12 h, 24% at 24 h, and 7.6% at 72 h. The HF was lower at 6 h than that after radiation alone, but was similar at later periods. After three fractions of 5 Gy with or without KU-2285, the HF was 33% at 6 h in both groups, while it was 12% and 13% at 24 h for tumors pretreated with KU-2285 and those receiving radiation alone, respectively. However, a sensitizing effect of KU-2285 was indicated by the downward shift of the survival curves for tumors irradiated after exposure to this agent. CONCLUSION: Reoxygenation occurred quite efficiently in tumors receiving KU-2285 and 12 Gy. After fractionated irradiation, however, reoxygenation was similar in the KU-2285-pretreatment and irradiation alone groups. PMID- 8005821 TI - Radiosensitizing activity and pharmacokinetics of multiple dose administered KU 2285 in peripheral nerve tissue in mice. AB - PURPOSE: In a clinical trial in which a 2-nitroimidazole radiosensitizer was administered repeatedly, the dose-limiting toxicity was found to be peripheral neuropathy. In the present study, the in vivo radiosensitizing activity of KU 2285 in combination with radiation dose fractionation, and the pharmacokinetics of cumulative dosing of KU-2285 in the peripheral nerves were examined. METHODS AND MATERIALS: The ability of three nitroimidazoles, misonidazole (MISO), etanidazole (SR-2508) and KU-2285, to sensitize SCCVII tumors to radiation treatment has been compared for drug doses in the range 0-200 mg/kg. Single radiation doses or two different fractionation schedules (6 Gy/fractions x three fractions/48 h or 5 Gy/fractions x five fractions/48 h) were used; the tumor cell survival was determined using an in vivo/in vitro colony assay. The pharmacokinetics in the sciatic nerves were undertaken, when KU-2285 or etanidazole were injected at a dose of 200 mg/kg intravenously one, two, three or four times at 2-h intervals. RESULTS: At less than 100 mg/kg, KU-2285 sensitized SCCVII tumors more than MISO and SR-2508 by fractionated irradiation. Evaluation of pharmacokinetics in the peripheral nerves showed that the apparent biological half-life of SR-2508 increased with the increases in the number of administrations, whereas that of KU-2285 became shorter. CONCLUSION: Since most clinical radiotherapy is given in small multiple fractions, KU-2285 appears to be a hypoxic cell radiosensitizer that could be useful in such regimens, and that poses no risk of chronic peripheral neurotoxicity. PMID- 8005820 TI - Comparison of radiosensitizing effect of KU-2285 and SR-2508 at low drug concentrations and doses. AB - PURPOSE: Since the radiosensitizing effect of KU-2285 at relatively low dose levels is not known, we investigated its efficacy at such low concentrations or doses achievable in humans with oral administration of 0.3-1.0 g/m2. METHODS AND MATERIALS: KU-2285 was tested in comparison with SR-2508 at low concentrations (0.05-0.25 mM) in vitro by the cytokinesis-block micronucleus assay and by the colony formation assay, and at low drug doses (12.5-50 mg/kg) in vivo by the in vivo-in vitro assay and by the growth delay assay using SCC VII tumors in C3H/He mice. RESULTS: In the cytokinesis-block micronucleus assay, the sensitizer enhancement ratio (SER) for KU-2285 and SR-2508 was 1.43 and 1.17 at 0.05 mM, 1.75 and 1.27 at 0.10 mM, and 2.14 and 1.69 at 0.25 mM, respectively. In the colony formation assay, the SER for KU-2285 was also greater than that for SR 2508. In the in vivo-in vitro assay, the SER for KU-2285 and SR-2508 was 1.11 and 1.04 at 12.5 mg/kg, 1.21 and 1.04 at 25 mg/kg, and 1.26 and 1.18 at 50 mg/kg, respectively. In the growth delay assay at 50 mg/kg, no tumor regrowth was observed in four of the 18 mice treated with KU-2285 + 25 Gy, although the growth delay time for the remaining mice was similar to that for SR-2508 + 25 Gy. CONCLUSION: KU-2285 was more effective than SR-2508 both at low drug concentrations in vitro and at low drug doses in vivo. These promising findings suggest the potential superiority of KU-2285 over SR-2508 as a radiosensitizer for clinical use. PMID- 8005822 TI - KIN-804 vs. KU-2285 as a radiosensitizer for clinical use. AB - PURPOSE: The in vitro and in vivo effects of two promising hypoxic cell radiosensitizers, KIN-804 (KIN) and KU-2285 (KU), were compared using four types of assays, and the acute toxicity and pharmacokinetics of KIN were investigated to evaluate the clinical applicability of the compounds. METHODS AND MATERIALS: To evaluate the in vitro effect at low radiation doses (1-4.5 Gy), the cytokinesis-block micronucleus (MN) assay using SCCVII or EMT-6 cells and the chromosomal aberration (CA) assay using EMT-6 cells were performed. In addition, an in vivo-in vitro colony assay, a growth delay assay, and a pharmacokinetic study were performed using C3H mice bearing SCCVII tumors, and the LD50/7 was determined in ICR mice. RESULTS: In the in vitro MN assay, the sensitizer enhancement ratio (SER) at 0.1, 0.25, 1, and 5 mM with SCCVII cells, and at 1 mM with EMT-6 cells was respectively, 1.45, 1.61, 2.57, 4.22, and 1.96 for KIN, and 1.57, 1.62, 2.59, 5.66, and 2.21 for KU. In the in vitro CA assay, the SER at 1 mM was 1.78 for KIN and 1.79 for KU. In the in vivo-in vitro colony assay, the SER of KIN at 50, 100, and 200 mg/kg was 1.24, 1.30, and 1.45, respectively, while the SER of KU at 100 mg/kg was 1.41. In the growth delay assay, the growth delay time for 100 and 200 mg/kg of the drug plus 20 Gy of radiation was respectively, 16.5 and 19.1 days for KIN, and 18.9 and 24.0 days for KU. In all experiments, the sensitizing effect of KIN was almost equal to that of KU. The LD50/7 of KIN was 3.6 g/kg by intraperitoneal injection, while that of KU was 3.6 g/kg by intraperitoneal injection, and the pharmacokinetic study of KIN revealed a low uptake of the drug by the brain. CONCLUSION: Both KIN and KU had a definite sensitizing effect even at lower drug concentrations or doses, suggesting their potential usefulness in clinical radiotherapy. PMID- 8005823 TI - In vivo radiosensitizing effect of nitroimidazole derivative KIN-804. AB - PURPOSE: In vivo characteristics of 2-nitroimidazole-1-methylacetohydroxamate (KIN-804), which is a newly developed hypoxic cell radiosensitizer, are presented. METHODS AND MATERIALS: The toxicity, pharmacokinetics, and radiosensitizing effect of KIN-804 were studied by in vivo experiments using C3H/He mice bearing the SCC-VII tumor. Results were compared with misonidazole (MISO). RESULTS: LD50(7) of KIN-804 and MISO were 3200 mg/kg and 2000 mg/kg, respectively. The peak of concentrations of KIN-804 in the tumor occurred 20 min after intraperitoneal injection and reached about 62% of the maximum concentration in the blood. The concentrations in brain and sciatic nerve were very low and clearance from sciatic nerve was rapid. Enhancement ratios of KIN 804 calculated using the growth delay method were 1.22, 1.50 and 1.71 at doses of 50, 100, and 200 mg/kg, respectively, compared with 1.36 for MISO at a dose of 100 mg/kg. In the TCD50 assay, enhancement ratios at a dose of 200 mg/kg were 1.69 for KIN-804 and 1.52 for MISO, respectively. CONCLUSION: KIN-804 is a promising radiosensitizer since it shows less toxicity and higher radiosensitizing activity than MISO. PMID- 8005824 TI - Clinical pharmacokinetic study and sensitive effect of AK-2123. AB - PURPOSE: The pharmacokinetic parameters of a radiosensitizer, AK-2123 given to 10 lung cancer patients are represented and its sensitizing effect is evaluated. METHODS AND MATERIALS: Ten patients with lung cancer: eight males, two females. The diagnosis was confirmed radiologically and pathologically. Seven patients were diagnosed with squamous cell cancer, two had adenocarcinoma, and one had nonsquamous cell lung cancer. AK-2123 was administered orally twice a week. The total dose per patient was 12.8-15.75 g. Radiotherapy was delivered 3 h after AK 2123 administration, 2 Gy per fraction. Blood samples were taken from the ear at 1, 3, 6, 9, 12, and 24 h after AK-2123 administration. The concentration of AK 2123 in plasma was measured by HPLC. RESULTS AND CONCLUSIONS: The Cm (maximum concentration of AK-2123 averaging from 10 patients) was 27.75 micrograms/mL, ranging 22.62-39.97 micrograms/mL, Tm (the time of getting Cm) 3 h. The data of the drug fitted a two-compartment open model. The mean parameteds of these cases were: rate constant K12 0.1658, K21 0.0671, Ke 0.0254, h-1; apparent volumes of distribution V1 18.6154, V2 51.2317, L; biological half life T1(2)a 1.0863, T1(2) alpha 2.7546, T1(2) beta 35.2064 h. The response to the treatment: CR four cases, PR four cases, NC two cases. So, AK-2123 may be a promising radiosensitizer. PMID- 8005825 TI - A phase I study of etanidazole and radiotherapy in malignant glioma. AB - PURPOSE: To determine the maximum tolerable total dose (MTD) of etanidazole (ETA) when administered with external beam radiotherapy (XRT) and as a continuous infusion during stereotactic brachytherapy for patients with malignant glioma (anaplastic astrocytoma or glioblastoma multiforme or mixed cell tumors). METHODS AND MATERIALS: Seventy previously untreated patients were entered in a Phase I study. Prior to initiation of treatment, patients were stratified according to whether or not they were candidates for interstitial implantation. The implant patients (IMP, n = 17 pt) received accelerated fractionation XRT 20 Gy BID (6 h apart) to 40 Gy in 2 weeks with ETA 2 gm/m2 x 6 doses, a 2 week break and then interstitial implant to 50 Gy (4-7 days) with a continuous infusion of ETA over 90-96 h. The two sequentially conducted nonimplant arms started with accelerated fractionation XRT 2 Gy BID (6 h apart) to 40 Gy in 2 weeks with ETA 2 gm/m2 x 4-5 doses/week. NonIMP 1 arm (n = 38) received a 2-week break before standard fractionated boost XRT of 20 Gy/day for 2 weeks to a total dose of 60 Gy with ETA. NonIMP 2 arm (n = 14) did not have the 2-week break. All patients had plasma pharmacokinetic monitoring of ETA. RESULTS: The dose-limiting toxicity (DLT) in the IMP group was the cramping/arthralgia syndrome (4) and the cumulative MTD was 26 gm/m2. For both nonIMP 1 and 2 the DLTs were peripheral neuropathy and the cramping-arthralgia syndrome. The MTD for nonIMP 1 was 34 gm/m2 and nonIMP 2, 30 gm/m2. CONCLUSION: The clinical efficacy and radiation-related toxicity of these regimens are being evaluated. The doses of ETA that can be used with accelerated fractionation and with external beam irradiation plus brachytherapy have been established. PMID- 8005826 TI - Accelerated bone marrow recovery from radiation damage in etoposide-pretreated mice. AB - PURPOSE: Etoposide inhibits the activity of Topoisomerase II, and possesses radiosensitizing effects on cultured cells. We showed that pretreatment of mice with etoposide 1 day before whole-body irradiation (WBI) had a protective effect against radiation-induced bone marrow death. The number of endogenous colony forming units (CFU-S) surviving in WBI mice was significantly increased by pretreatment with etoposide. The purpose of the present study is to clarify mechanisms underlying the protective activity of etoposide against radiation induced bone marrow damage. METHODS AND MATERIALS: The spleen colony-forming cells (CFU-S) of femoral marrow were assayed by the method of Till and McCulloch. The proliferative state of CFU-S was assessed using the technique of Hodgson. The reduction in exogenous CFU-S after hydroxyurea injection was used to determine the fraction size of S-phase in CFU-S. RESULTS: Etoposide pretreatment did not modify the cell survival parameters of exogeneous CFU-S when bone marrow cells were assayed immediately after WBI. Recovery of CFU-S in femoral marrow started earlier in mice receiving etoposide pretreatment than in the radiation alone group. Administration of hydroxyurea revealed that the accelerated recovery of CFU-S was due to an increased population of S phase cells, suggesting etoposide pretreatment shortened generation time of CFU-S. CONCLUSIONS: The mechanism for the radioprotection appears to be accelerated proliferation of survived bone marrow cells rather than a change in cellular sensitivity to radiation. PMID- 8005827 TI - Effects of combination of immunomodulators and an adrenochrome derivative on survival of irradiated mice. AB - PURPOSE: The combined effects of immunomodulators (lithium or OK432) and an adrenochrome derivative (AMM), an agent found to activate granulocyte-macrophage colony stimulating activity, on the survival of irradiated ddY mice is described. METHODS AND MATERIALS: ddY mice at 4-5 weeks old were whole body irradiated with X rays at 8.5 Gy. Sole injection and combined injection of AMM and/or one of the immunomodulators were performed before or after irradiation. Then, survival was monitored daily for 30 days after irradiation. RESULTS: Lithium at 60 mg/kg had no radioprotective effect; rather it accelerated radiation induced death. Sole treatment with AMM (100 mg/kg) had no effect on survival of irradiated mice. However, combination of both drugs caused a slight radioprotection. OK432 (25 KE/kg), which activates a variety of cellular effector cells had radioprotective effect. When combined with AMM, however, it totally lost radioprotective effect. CONCLUSION: Lithium chloride cannot be used as a radioprotector because of its adverse effect. Combination with AMM showed slight radioprotection, but the extent thereof may not be clinically useful. OK432 was proved to be a potent radioprotector. However, combination with AMM should be avoided, since the radioprotection was totally eliminated. PMID- 8005828 TI - In vitro effects of OK-432 on irradiated mouse bone marrow cells. AB - PURPOSE: In vitro effects of OK-432 on irradiated mouse bone marrow cells are examined. METHODS AND MATERIALS: Bone marrow cells of BDF1 mouse (1 x 10(6) cells/ml) were incubated with alpha medium, 2% fetal calf serum and OK-432 in a CO2 incubator at 37 degrees C for 24, 48 and 72 h, respectively. After centrifugation, each supernatant was collected and used for conditioned medium in CFU-GM assay: Changes in CFU-GM as a function of incubation time and OK-432 dose was examined; changes of CFU-GM according to various doses of OK-432 were examined in two mouse strains, BDF1 and BALB/c mouse; changes in protective effect of OK-432 in terms of CFU-GM as a function of administration timing of OK 432 in relation to irradiation. As a radiation source, 137Cs at a dose rate of 500 cGy/min was used. RESULTS: The CFU-GM decreased with the incubation time when OK-432 was not administered, while it significantly increased with incubation time when OK-432 was added at 0.5 and 1.0 KE/ml at 48-72 h of incubation. The former showed marked increase at 48-72 h of incubation. CFU-GM of BDF1 mouse was always higher than that of BALB/c mouse for any dose of OK-432. CFU-GM per femur according to the timing of administration of OK-432 from 24 h before to 24 h after irradiation showed 10299 +/- 2300 (24 h before), 10783 +/- 2463 (3 h before), 10045 +/- 1501 (immediately after), 8504 +/- 1188 (3 h after), 4898 +/- 1212 (6 h after), 1214 +/- 736 (12 h after) and 181 +/- 113 (24 h after irradiation), respectively. CONCLUSION: OK-432 stimulates cultured mouse bone marrow cells to produce GM-CSF in vitro by direct contact action. This direct stimulating action of OK-432 on GM-CSF production of bone marrow cells can be kept from 24 h before to at least 3 h after irradiation. PMID- 8005829 TI - Differential action on cancer and normal tissue by adrenochrome monoaminoguanidine methanesulfonate and cytochrome C combined with radiotherapy. AB - PURPOSE: The possibility that radioprotective effects on potent natural killer (NK) cells by adrenochrome monoaminoguanidine methanesulfonate+cytochrome C during radiotherapy (RT) for lung cancer might result in the radiosensitization of human lung cancer cells in vivo is examined. METHODS AND MATERIALS: Human lung cancer xenografts in the right hind legs of KSN mice (10 weeks old) were locally irradiated with 20 Gy of X ray. Adrenochrome monoaminogluanidine methanesulfonate (AMM) (10 mg/kg/day) and/or cytochrome C (CCC) (5 mg/kg/day) were given intraperitoneally immediately before or after RT, followed by daily administration for 4 days. Natural killer activities of host splenocytes were also tested with the standard 51Cr releasing assay with YAC-1 cells as target cells. In a clinical study, 65 patients with lung cancer were treated with more than 50 Gy of RT with or without combination with AMM+CCC, OK-432 or AMM+CCC+OK 432. Before and after RT, lymphocyte subsets in the peripheral blood were examined with dichromatic analysis using an Ortho Spectrum IIIFCM system and fluorescent MABs. In this study, the change in the absolute number of each subset was investigated. RESULTS: Adrenochrome monoaminoguanidine methanesulfonate+cytochrome C augumented NK activity in KSN nude mice, protected potent NK cells in patients with lung cancer against RT and sensitized the human lung cancer xenografts to RT. CONCLUSION: Adrenochrome monoaminoguanidine methanesulfonate+cytochrome C may have the potential as a differential modulator of radiosensitivity of normal tissues and of tumors. PMID- 8005830 TI - Production of histamine and tyramine by lactic acid bacteria isolated from vacuum packed sugar-salted fish. AB - The incidence of histamine- or tyramine-producing lactic acid bacteria was examined in several products of vacuum-packed sugar-salted fish (salmon, halibut, mackerel). No histamine-producing isolates were observed, whereas the majority of tyramine-producing isolates were identified as Carnobacterium spp. These organisms were shown to be important members of the microbial flora during storage of vacuum-packed sugar-salted salmon at 5 degrees C. The amount of tyramine produced was reduced by lowering the temperature from 9 degrees C to 4 degrees C for all of five strains of carnobacteria or lactobacilli. The majority of tyramine was produced during the exponential growth phase for Carnobacterium piscicola N 5 and Lactobacillus viridescens N 69. The ability of these bacteria to produce tyramine may be used as an index of microbial quality/acceptability of stored vacuum-packed sugar-salted fish. PMID- 8005831 TI - Continuous culture studies on the synthesis of capsular polysaccharide by Klebsiella pneumoniae K1. AB - The synthesis of capsular polysaccharide by Klebsiella pneumoniae K1 was investigated in a minimal salts medium by continuous culture. The organism produced larger amounts of polysaccharide under nitrogen-limited conditions than under carbon-limited conditions. The synthesis of polysaccharide was dependent not only on the availability of excess carbon, but also on growth rate. The rate of polysaccharide synthesis was greatest at low dilutions, low temperature (30 degrees C) and at neutral pH. Prolonged growth in nitrogen-limited culture resulted in the development of non-mucoid variants, possibly due to a selective growth advantage over mucoid cells. The non-mucoid isolate was more susceptible to some bacteriophages, possibly due to the reduction nor absence of capsular polysaccharide. PMID- 8005832 TI - Genetic studies of lactococcal bacteriophages--taxonomic differentiations and DNA analysis: evidence for 3' cohesive ends. AB - Twenty-four bacteriophages of Lactococcus lactis subsp. lactis and L. lactis subsp. cremoris were classified. Two groups of bacteriophages morphologically defined as prolate or isometric types by electron microscopy were examined for their genome sizes, protein patterns and DNA homologies. These criteria showed that prolate phages are quite homogeneous. In contrast, isometric phages exhibit more differences, particularly in particle sizes and protein compositions. Analysis of DNA hybridizations confirmed that prolate phages can be grouped together as can be isometric phages but for one exception, phage I52. These two families were clearly defined. The unique phage which does not fit in either group probably belongs to a third one which is much less represented. No obvious relationships between these criteria and the lytic spectra were detected. Evidence of the presence of cohesive ends in phage genomes is also presented in this study. A more detailed analysis performed on one member of the prolate group revealed 3' protruding ends made up of around 13 nucleotides on complementary single strands. PMID- 8005833 TI - A comparison of conventional SEM techniques, low temperature SEM and the electroscan wet scanning electron microscope to study the structure of a biofilm of Streptococcus crista CR3. AB - Biofilms of Streptococcus crista CR3 were generated on hydroxyapatite (HA) discs for 20 h in a continuous flow system with brain heart infusion broth dripped over the disc at a rate of 6 ml h-1. This study compares the conventional scanning electron microscope (SEM) preparation techniques, of critical point drying and freeze-drying, with low temperature SEM (LTSEM) and Electroscan generated images of hydrated biofilms, which preserve the integrity of hydrated polymers. Critical point drying and freeze-drying caused almost complete disappearance of the matrix of extracellular polymeric substances (EPS). Critical point drying, however, showed evenly spaced single or paired cocci remaining on the HA disc whereas freeze-drying caused the biofilm to detach from the HA leaving only patchy clumps of cells visible. By comparison LTSEM preserved the EPS better than critical point drying and freeze-drying, but holes were seen in the top and side of the biofilm and the EPS did show some shrinkage artefacts. An untreated wet biofilm viewed in the Electroscan showed an intact, hydrated, smooth matrix of EPS with cell shapes only visible indistinctly in a canopy of moist EPS. No holes were visible and no shrinkage artefacts were evident. Therefore, Electroscan imaging of the biofilm was the only method that preserved the integrity of the matrix with no apparent shrinkage artefacts. PMID- 8005835 TI - Interaction of iodine with Bacillus subtilis spores and spore forms. AB - Buffered solutions of iodine (pH 7.0) were effective against Bacillus subtilis spores, but concentrations and contact times for effective sporicidal action were relatively high. Concentrations of 500 to 1000 ppm available iodine with a contact time of 30-45 min were required to produce a 3-5 log reduction. Treatment of spores with agents which caused progressive extraction of coat protein and cortex hexosamine was associated with increased sensitivity to iodine. Treatment of spores with iodine produced extraction of spore coat protein which was potentiated in the presence of NaOH, but there was no evidence of breakdown of cortex hexosamines or release of dipicolinic acid, either from intact spores or spore protoplasts. Sporicidal concentrations of iodine stimulated the uptake of (32P) phosphate over an initial period of 30-40 min, but phosphate then leaked from the cells; 1000 ppm available iodine produced total loss within 60 min. Results of this investigation are consistent with previous findings which suggest that the resistance of spores to biocides is related to the barrier properties of the spore outer layers and that the sporicidal action of halogen-releasing agents is related to their ability to cause coat and cortex degradation, leading to rehydration of the spore protoplast and allowing diffusion to their site of action on the underlying protoplast. PMID- 8005834 TI - Microbiological evaluation of jejunal aspirates and faecal samples after oral administration of bifidobacteria and lactic acid bacteria. AB - A double-blind placebo controlled investigation was carried out to study the effect of peroral colonization. Human volunteers were given mixtures of bifidobacteria and lactic acid bacteria. Measurements were made over a 1 week treatment period and for another week after the end of the treatment. Two different bacteriological preparations were used, one consisted of Enterococcus faecium and Bifidobacterium longum (a total of 6.4 x 10(8) cfu d-1); the other consisted of Lactobacillus acidophilus, Bif. bifidum, Lact. delbrueckii ssp. bulgaricus, and Streptococcus thermophilus (a total of 9 x 10(9) cfu d-1). Together with a placebo preparation, they were given to 24 healthy controls (eight in each group). Microbiological examinations of jejunal aspirates showed that viable counts of most species were below the detection limit. However, the test preparation containing Ent. faecium and Bif. longum significantly reduced the anaerobe: aerobe ratio in faeces by a factor of three during treatment (P = 0.03), and increased it by a factor of 30 during the following week (P < 0.02). This study shows that peroral administration of certain bacterial cultures may affect the distal intestinal microflora. PMID- 8005836 TI - Characteristics of 'atypical', cytochrome oxidase-negative Aeromonas salmonicida isolated from ulcerated flounders (Platichthys flesus (L.)). AB - 'Atypical', cytochrome oxidase-negative variants of the fish pathogen Aeromonas salmonicida, isolated from ulcerated flounder (Platichthys flesus), were studied using different methods. Two of the strains possessed a protein that corresponded to the A-layer protein of Aer. salmonicida. The strains reacted with antibodies against the A-layer and monoclonal antibodies against the O-antigen of typical Aer. salmonicida. These tests confirm that the isolates from flounder should be classified as Aer. salmonicida. Analysis of the fatty acids showed that the isolates were rather homogeneous but the values of the guanine plus cytosine content of the DNA of the bacteria varied too much for any conclusion to be drawn on their taxonomic location. The strains examined exhibited several biochemical characters that differed from those of the type strains of Aer. salmonicida subsp. salmonicida and Aer. salmonicida subsp. achromogenes. The results suggest that these 'atypical', cytochrome oxidase-negative variants may form a new subspecies of Aer. salmonicida. PMID- 8005837 TI - Microflora on explanted silicone rubber voice prostheses: taxonomy, hydrophobicity and electrophoretic mobility. AB - Silicone rubber voice prostheses are implants which are inserted in a non-sterile environment and therefore become quickly colonized by micro-organisms. The micro organisms exist on the medical grade silicone rubber as mixed biofilms of bacteria and yeasts. A total of 79 bacterial and 39 yeast strains were isolated from these biofilms by soft ultrasonic treatment. Gram-positive/catalase-negative and Gram-positive/catalase-positive cocci represented the dominant bacterial strains. The yeasts were mainly Candida species. Further characterization of cell surface properties such as hydrophobicity by microbial adhesion to hexadecane and electrophoretic mobility showed a distinct difference when the bacterial strains were compared with the yeasts. The bacterial hydrophobicities ranged from 0 to 100% adhesion to hexadecane, whereas the yeast strains, especially the Candida albicans strains, all had markedly hydrophilic cell surfaces. A comparison of the electrophoretic mobilities showed also differences between bacteria and yeast. The values for the bacteria were found to be between -2.5 to -0.5 (10(-8) m2 V-1 s-1), whereas for the yeasts electrophoretic mobilities were more positive. Based on the adhesive properties of the isolated micro-organisms, strategies can now be developed to modify the properties of the silicone rubber to reduce biofilm formation on such prostheses. PMID- 8005839 TI - Small-amplitude pressure oscillations do not modify respiratory mechanics in rabbits. AB - Changes in respiratory mechanics have occasionally been observed during high frequency ventilation. In this study we investigated whether small pressure oscillations such as those used for respiratory impedance measurements modified total respiratory resistance (Rrs) and total respiratory elastance (Ers). The latter were measured in six paralyzed artificially ventilated rabbits with and without superimposed pressure oscillations at the airway opening. Rrs and Ers were obtained by least square fitting of low-pass filtered tracheal pressure and flow to the usual first-order model. Pressure oscillations of 2-4 hPa peak-to peak at 10, 20, and 30 Hz applied for periods of 10 min had virtually no effect on Ers (changes ranging from -2.5 to 2.6%) and Rrs (0-8.2%). Analysis of variance did not show a significant difference on the pooled data. Pressure oscillations were also applied every other minute after a histamine aerosol. Ers and Rrs were similarly unchanged. We conclude that the small pressure oscillations used in respiratory impedance measurements do not modify lung mechanical properties and lung response to bronchomotor agents. PMID- 8005838 TI - Natural surfactant and hyperoxic lung injury in primates. II. Morphometric analyses. AB - Diffuse lung injury is accompanied by low compliance and hypoxemia with histological evidence of endothelial and alveolar epithelial cell disruption. The histological effects of treatment of an acute diffuse lung injury with a natural surfactant product were evaluated in a primate model because surfactant function and content have been shown to be abnormal in diffuse lung injury in both animals and humans. Ten baboons were ventilated with 100% O2 for 96 h, and 5 were given an aerosol of natural porcine surfactant. Physiological and biochemical measurements of the effects of hyperoxia and surfactant treatment are presented in a companion paper. After O2 exposure, lungs were fixed and processed for quantitative electron microscopy. The responses to O2 included epithelial and endothelial cell injuries, interstitial edema, and inflammation. The hyperoxic animals treated with surfactant were compared with the untreated animals; the treatments altered neutrophil distribution, fibroblast proliferation, and changes in the volumes of type I epithelial cells and endothelial cells. Surfactant treated animals also had decreased lamellar body volume density in type II epithelial cells and preservation of endothelial cell integrity. These changes suggest complex effects of natural surfactant on the pulmonary response to hyperoxia, including protection against epithelial and endothelial cell destruction as well as significant interstitial inflammation and fibroblast proliferation. We conclude that natural surfactant treatment of hyperoxic lung injury in primates resulted in partial protection of epithelial and endothelial cells but also increased the accumulation of fibroblasts in the lung. PMID- 8005840 TI - Respective oxidation of exogenous glucose and fructose given in the same drink during exercise. AB - We computed the respective amounts of exogenous glucose (G) and fructose (F), which are oxidized during exercise when ingested simultaneously, with the use of 13C labeling. Six subjects exercised for 2 h at 60.7 +/- 2.9% of maximal O2 uptake on a cycle ergometer while ingesting 50 or 100 g of G or F or a mixture of 50 g each of G and F in 500 ml of water. The amount of exogenous G oxidized increased from 37.8 +/- 2.2 to 58.3 +/- 8.1 g when the total amount ingested increased from 50 to 100 g. The amount of F oxidized was significantly lower (32.2 +/- 1.2 and 45.8 +/- 2.6 g for the 50 and 100 g ingested, respectively). When 50 g each of G and F were simultaneously ingested in the same drink, the amounts oxidized (39.5 +/- 4.8 and 34.1 +/- 1.5 g, respectively) were similar to those observed when 50 g of G or F were ingested separately. The cumulative amount of exogenous hexoses oxidized (73.6 +/- 6.6 g) was 21% larger than when 100 g of G were ingested. This finding could be due to the fact that the routes for absorption and metabolism of exogenous G and F are at least partly different, resulting in less competition for oxidation when a mixture of these two hexoses is ingested than when an isocaloric amount of G is ingested. From a practical point of view, these data may provide experimental support for using mixtures of carbohydrates in the energy supplements for endurance athletes. PMID- 8005841 TI - Severe VA/Q mismatch in perfused lungs evoked by sequential challenge with endotoxin and E. coli hemolysin. AB - Escherichia coli hemolysin (ECH), an important pathogenicity factor in extraintestinal E. coli infections, provokes pulmonary hypertension and microvascular leakage in buffer-perfused rabbit lungs. We investigated gas exchange abnormalities in response to low doses of ECH, lipopolysaccharides (LPS), and sequential and combined application of these bacterial agents by using the multiple inert gas elimination technique. In control lungs and after admixture of 100 ng/ml of LPS, unimodal narrow distribution of perfusion and ventilation to midrange ventilation-perfusion (VA/Q) areas was noted. ECH [0.08 hemolytic units (HU)/ml] caused a moderate increase in pulmonary arterial pressure (< 10 mmHg), progressive lung edema formation (approximately 10 g within 20 min), and a broadening of perfusate and gas flow dispersion. Application of 0.08 HU/ml of ECH in lungs "primed" with 100 ng/ml of LPS in a preceding 125-min perfusion period provoked a large increase in pulmonary arterial pressure (> 50 mmHg within 5 min), rapid edema formation (approximately 10 g within 10 min), and severe VA/Q mismatch with predominance of shunt flow. Vasoconstrictor response and VA/Q mismatch, but not edema formation, were largely inhibited by pretreatment of lungs with acetylsalicylic acid or the thromboxane receptor antagonist BM-13.505. In addition, "rescue" application of BM-13.505 rapidly reversed pressure rise and shunt flow due to sequential LPS and/or ECH stimulation, whereas edema formation was not affected. We conclude that the marked pulmonary hypertension in response to low doses of ECH in LPS-primed lungs is paralleled by severe gas exchange abnormalities with predominance of shunt flow. Both the vasoconstrictor response and the development of shunt are closely related to toxin-induced thromboxane generation. PMID- 8005842 TI - Kinetics of lactate transport in sarcolemmal giant vesicles obtained from human skeletal muscle. AB - We developed a method that allows the measurement of muscle lactate transport in humans. The transport studies were carried out with giant (1.8- to 36-microns diam) sarcolemmal vesicles obtained by collagenase treatment of needle biopsy material. Marker enzyme analyses demonstrated that the vesicular membrane is predominantly of sarcolemmal origin, contamination with sarcoplasmic reticulum membranes is very low, and mitochondrial membranes are not a major contaminant. The vesicles were loaded with labeled lactate, and the efflux was measured. The system displayed saturation kinetics and inhibitor sensitivity. In equilibrium exchange experiments (pH 7.4, 21 degrees C), the Michaelis-Menten constant (Km) for the carrier-mediated flux was 30 +/- 8 (SD) mM and maximal transport rate (Vmax) was 184 +/- 24 pmol.cm-2.s-1 (142 nmol.mg protein-1.min-1). In zero-trans efflux experiments, Km was 24 +/- 8 mM and Vmax was 81 +/- 11 pmol.cm-2.s-1 (63 nmol.mg protein-1.min-1). In infinite-cis experiments with a variable lactate concentration on the outside of the vesicles, Km was 8 +/- 4 mM and Vmax was 136 +/- 9 pmol.cm-2.s-1 (105 nmol.mg protein-1.min-1). Thus, the system displayed transacceleration. Low pH (6.4) had no significant effect on equilibrium exchange experiments, whereas in zero-trans experiments low pH at the trans side inhibited the flux by 50%. We concluded that lactate transport can be studied in giant vesicles obtained from a single human muscle biopsy. Our data provide evidence for the existence of a lactate carrier in human sarcolemma. This transport system must be taken into account in models of human lactate kinetics. PMID- 8005843 TI - Effects of acute caffeine withdrawal on habituated male runners. AB - This study investigated the effects of caffeine withdrawal on six trained caffeine-habituated male runners: age 29.8 +/- 5.8 (SD) yr, height 180.4 +/- 5.4 cm, weight 77.3 +/- 6.7 kg, maximal O2 uptake 63.0 +/- 5.4 ml.kg-1.min-1, and daily caffeine intake 674 +/- 128 mg. The subjects received a loading dose (5 mg/kg body wt) of caffeine 48 h before each testing session. They were then given (using a repeated-measures double-blind design) additional doses of caffeine (5 mg/kg body wt) or a placebo 36, 24, 12, and 2 h before testing. They ran at a velocity corresponding to their lactate threshold for 60 min in a caffeine withdrawal or caffeinated condition. Caffeine withdrawal resulted in no significant differences in absolute O2 uptake, O2 uptake relative to maximal O2 uptake, respiratory exchange ratios, or free fatty acid concentrations. Glycerol concentrations were significantly attenuated in the withdrawal condition. No significant differences were revealed in calculated substrate utilization. It was concluded that caffeine withdrawal significantly affects lipolysis but not substrate utilization during prolonged running. PMID- 8005844 TI - Adrenergic status of humans during prolonged exposure to the altitude of 6,542 m. AB - Plasma norepinephrine (NE) concentration increases with altitude exposure while maximal heart rate (HR) and chronotropic response to isoproterenol (IP) are blunted. Downregulation of cardiac beta-adrenergic receptors (beta-AR) has been evoked to explain this phenomenon. Chronotropic response was studied at extreme altitude in 10 subjects (4 women, 6 men; aged 35 +/- 6 yr). Observations were made in normoxia (N) and after 1 (H1) and 3 (H3) wk at 6,542 m. Acclimatization was accomplished by gradual climbing from 4,000 to 6,542 m over 10 days. Plasma NE was obtained at rest and during submaximal exercise. Successive doses of IP (0.02, 0.04, and 0.06 microgram/kg-1.min-1) were infused for 5 min each. Density and affinity of lymphocyte beta 2-AR were also measured. Increase in HR for maximal dose of IP decreased from 57 +/- 12 to 34 +/- 7 and 37 +/- 10 min-1 in H1 and H3, respectively (P < 0.001 for both). IP dose for which HR rises by 25 min-1 (I25) increased from 27 +/- 5 in N to 42 +/- 10 and 43 +/- 17 ng.kg-1.min-1 in H1 and H3, respectively (P < 0.001 for both). Arterial O2 saturation at rest was 98 +/- 2% in N, 72 +/- 6% in H1 (P < 0.001), and 79 +/- 5% in H3 (P < 0.001). The chronotropic response was neither restored nor further attenuated after 3 wk at 6,542 m. Plasma NE levels at rest and during exercise were higher at 6,542 m than values obtained in previous studies at 4,350 and 4,800 m.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8005845 TI - Decrease in left ventricular contractility after tumor necrosis factor-alpha infusion in dogs. AB - Whether systolic contractility or diastolic compliance changes soon after tumor necrosis factor-alpha (TNF-alpha) exposure is not known. Accordingly, we measured hemodynamics, left ventricular contractility using the slope of the end-systolic pressure-volume relationship, and diastolic pressure-volume relationships in six control dogs and in six dogs receiving 60 micrograms.kg-1.h-1 i.v. of TNF-alpha. Mean aortic pressure decreased by 22% 1 h after TNF-alpha infusion and remained decreased (P < 0.05). Cardiac output increased by 19% 1 h after TNF-alpha infusion and remained significantly greater than control values (P < 0.05). Left ventricular contractility decreased by 23% (P < 0.05) 1 h after TNF-alpha infusion and decreased by 52% (P < 0.01) 5 h after TNF-alpha infusion. The diastolic pressure-volume relationship did not change in the TNF-alpha group or the control group. Ejection fraction did not change after TNF-alpha infusion despite the decrease in contractility because afterload decreased. We conclude that TNF-alpha is important in causing the hypotensive, hyperdynamic circulation of sepsis. The new finding that left ventricular contractility is decreased shortly after TNF-alpha infusion suggests that TNF-alpha, or another mediator released very soon after TNF-alpha, is an important myocardial depressant factor. PMID- 8005846 TI - Time course of erythropoietin, triiodothyronine, thyroxine, and thyroid stimulating hormone at 2,315 m. AB - Erythropoietin (EPO), triiodothyronine, thyroxine, thyroid-stimulating hormone (TSH), hemoglobin (Hb), reticulocytes, packed cell volume, and plasma volume changes were studied in 29 male Austrian mountain rescue soldiers before and several days after an ascent from 744 to 2,315 m in the Alps. EPO concentrations showed a remarkable increase 48 h after the ascent (P < 0.01). No significant changes were found in triiodothyronine, thyroxine, and TSH. Reticulocytes increased only slightly. Hb decreased during the week (P < 0.01). Packed cell volume did not change, whereas plasma volume showed a slight decrease for 48 h after the ascent but then increased constantly (P < 0.01). It seems that thyroid hormones, TSH, and Hb play only a minor role in the regulation of EPO production and release under mild hypobaric-hypoxic conditions (2,315 m). PMID- 8005847 TI - Beta-carotene and CNS oxygen toxicity in rats. AB - Beta-carotenes are reported to be potent free radical quenchers, singlet oxygen scavengers, and lipid antioxidants. Oxygen free radicals that are produced in excess during exposure to oxygen at high pressures and overwhelm the body's normal antioxidant defense systems seem to mediate the hyperoxic insult. We decided to test the possible protective effect against central nervous system oxygen toxicity of a natural beta-carotene composed of equal amounts of the all trans and 9-cis isomers obtained from the unicellular halotolerant alga Dunaliella bardawil. Rats implanted with chronic cortical electrodes for continuous electroencephalogram monitoring were fed on ground commercial food enriched with natural beta-carotene (1 g/kg diet). On completion of 1 wk of the diet, the rats were exposed to 0.5 MPa oxygen and then their livers were removed for beta-carotene and vitamin A analysis. A significant increase was noted in the latent period preceding oxygen seizures in the group of rats in which the diet was supplemented by natural beta-carotene compared with rats given a normal diet (38.5 +/- 3.4 vs. 16.8 +/- 1.8 min; P < 0.05). Further experiments are required to evaluate the potential benefit of supplementing the diet of divers and patients exposed to high pressures of oxygen with the beta-carotene-rich D. bardawil. PMID- 8005848 TI - Sympathetic nerve activity during prolonged rhythmic forearm exercise. AB - Exercise is a potent stimulus to activate the sympathetic nervous system. Previous work suggests that metabolite-sensitive muscle afferents are activated near the point of fatigue, and, when activated, they determine the muscle sympathetic nerve activity (MSNA) response to isometric forearm exercise. Yet, studies using a more prolonged rhythmic exercise paradigm suggest that the sympathetic nervous system can be activated in a more graded fashion. The purpose of this study was to determine whether metaboreceptor stimulation would also be responsible for MSNA responses to prolonged rhythmic isotonic forearm exercise. Subjects (n = 16) performed rhythmic isotonic forearm exercise at 25% maximal voluntary contraction for 30 min as we measured MSNA (microneurography). We observed progressive increases in MSNA with a peak increase of 161 units from a baseline value of 180 units. We also performed posthandgrip circulatory arrest (PHG-CA) in nine of these subjects. This maneuver isolates the metaboreceptor contribution to MSNA. During PHG-CA, delta MSNA values were not different from those observed during a freely perfused recovery period (n = 7). We also compared MSNA responses during the rhythmic paradigm with those seen during a static protocol at 40% of maximal voluntary contraction in five subjects. The two types of exercise caused similar increases in MSNA, but only the static paradigm was associated with a sustained MSNA response during PHG-CA. Finally, 31P-nuclear magnetic resonance was used to evaluate muscle metabolic responses during rhythmic and static forearm exercise (n = 6). Static exercise caused muscle acidosis and an increase in H2PO4-, whereas rhythmic exercise had no effect on muscle metabolism.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8005849 TI - Effect of clonidine on induced cough and bronchoconstriction in guinea pigs and healthy humans. AB - We examined the effects of the alpha 2-receptor agonist clonidine, administered orally and by inhalation, on citric acid- and capsaicin-induced reflexes in guinea pigs and healthy human subjects. In groups (n = 8-10) of conscious guinea pigs, oral clonidine (10 and 100 micrograms/kg) was without effects, whereas inhaled clonidine (10-1,000 microM) caused a concentration-dependent inhibition of citric acid-induced cough (coughs during 3 min: control, 6.5 +/- 0.9; 1,000 microM clonidine, 1.7 +/- 1.0; P < 0.05) and reflex bronchoconstriction (time to onset of bronchoconstriction: control, 191 +/- 24 s; 1,000 microM clonidine, 317 +/- 33 s; P < 0.05). The inhibitory effect of inhaled clonidine on both reflexes was completely reversed by pretreatment with yohimbine but not with prazosin. In 12 healthy human volunteers, oral clonidine (150 mg) caused a significant fall in supine and erect systolic blood pressure and a significant increase in drowsiness as measured on a visual analogue scale 1 and 2 h after administration. Despite these effects, oral clonidine had no effect on capsaicin-induced cough or reflex bronchoconstriction in humans. In contrast to the effects in guinea pigs, inhaled clonidine (281 microM) had no effect on capsaicin-induced cough or reflex bronchoconstriction in humans. These data suggest that peripheral alpha 2 receptors exert an inhibitory effect on sensory neurotransmission in the guinea pig but not in the healthy human airway, indicating an important difference between the two species. PMID- 8005850 TI - Ozone-induced airway hyperresponsiveness and loss of neuronal M2 muscarinic receptor function. AB - The effect of acute ozone exposure on the function of efferent parasympathetic nerves, M3 muscarinic receptors on airway smooth muscle, and inhibitory M2 muscarinic receptors on the parasympathetic nerves was studied. Immediately after exposure to 2.0 ppm ozone for 4 h, guinea pigs became hyperresponsive to electrical stimulation of the vagus nerves. The normal airway response to intravenous cholinergic agonists at this time demonstrates normal M3 receptor function. M2 muscarinic receptors on the nerves, which normally inhibit release of acetylcholine, were dysfunctional after ozone exposure, as demonstrated by the failure of the muscarinic agonist pilocarpine to inhibit, and the failure of the M2 antagonist gallamine to potentiate, vagally mediated bronchoconstriction. Thus, loss of inhibitory M2 muscarinic receptor function after ozone exposure potentiates release of acetylcholine from the vagus nerves, increasing vagally mediated bronchoconstriction. By 14 days, postozone responses to vagal nerve stimulation were not different from those of air-exposed animals and the function of the neuronal M2 muscarinic receptor was normal, confirming that ozone-induced hyperresponsiveness is reversible. PMID- 8005852 TI - Psychophysiological reactions in humans during an open sea dive to 500 m with a hydrogen-helium-oxygen mixture. AB - Six commercial divers were investigated for neurological and psychosensorimotor responses during an open sea dive to 500 m with a hydrogen-helium-oxygen mixture containing 49% hydrogen. Results showed only moderate neurological symptoms of high-pressure nervous syndrome, whereas the narcotic effect of hydrogen was detectable, as investigated by psychosensorimotor tests. Nevertheless, the divers successfully carried out the main purpose of the operational dive, which was to prove the feasability of such diving methods by connecting specific elements of an offshore oil installation. Finally, these data support the hypothesis that hydrogen can alleviate some of the symptoms of the high-pressure nervous syndrome and can constitute a useful gas for commercial diving, as it decreases the density of the breathing mixture and therefore improves the living conditions, work, and comfort of the divers. Nevertheless, the present results underscore the relevance of research on individual susceptibility to pressure environment regardless of the composition of the breathing mixture. PMID- 8005851 TI - Modifications of glucose and lipid metabolism in cold-acclimated lean and genetically obese rats. AB - Glucose turnover rate, 2-deoxy-D-[3H]glucose (2-DG) uptake, lipid synthesis in liver, white adipose tissue, and brown adipose tissue (BAT) were measured in lean FA/FA and genetically obese fa/fa rats either kept at 21 degrees C or acclimated to a cold environment (4 degrees C). After 10 days at 4 degrees C, lean rats increased their glucose turnover rate; 2-DG uptake as well as lipid synthesis in BAT were markedly stimulated. After cold acclimation, obese rats also increased glucose turnover; however, BAT glucose utilization was only slightly stimulated. Basal hyperinsulinemia and muscle insulin resistance of the obese group (as assessed by reduced 2-DG uptake in the soleus muscle) were present at room temperature and persisted at 4 degrees C. Total BAT lipid synthesis was increased to the same extent as in lean rats. Obese rat liver lipid synthesis, already much higher than normal at 21 degrees C, was further increased by cold exposure. We conclude that obese cold-acclimated fa/fa rats do not improve their muscle insulin resistance and barely improve BAT glucose utilization. We further suggest that an additional activation of hepatic lipid synthesis and oxidation thereof could participate in the heat production needed by the cold-acclimated obese rats. PMID- 8005853 TI - Effect of simple carbohydrates, casein hydrolysate, and a lipid test meal on ethane exhalation rate. AB - To determine the potential differences in the effect of various nutrients on lipid peroxidation, the ethane exhalation (EE) rate, an index of lipid peroxidation, was measured in rats at 4 (young), 18 (intermediate age), and 24 (aged) mo of age at fasting conditions and after acute ingestion of various test meals. The EE rate (means +/- SD) after a 15-h fast was significantly reduced in 24-mo-old rats (2.45 +/- 0.44 pmol.min-1.100 g body wt-1) and 18-mo-old rats (3.51 +/- 0.55 pmol.min-1.100 g body wt-1) compared with 4-mo-old rats (4.44 +/- 0.66 pmol.min-1.100 g body wt-1; P < 0.01). The EE rate significantly increased in 4-mo-old rats after ingestion of 50% (wt/vol) dextrose (8.59 +/- 2.9 pmol.min 1.100 g body wt-1), 50% casein hydrolysate (6.77 +/- 1.23 pmol.min-1.100 g body wt-1), and 20% neutral lipid emulsion (7.33 +/- 1.96 pmol.min-1.100 g body wt-1; P < 0.01). The response of aged rats to these nutrients compared with young rats was reduced by approximately 50%. A 25% dextrose solution or a 50% solution of sucrose, fructose, maltose, or galactose did not significantly alter EE rate. It is concluded that various macronutrients have a diverse potential of inducing lipid peroxidation. The responsiveness of aged rats to meal-induced enhancement of EE and presumably lipid peroxidation is significantly reduced. PMID- 8005854 TI - Differential reflex control of forearm and calf resistance vessels by chemosensitive cardiac afferent activation. AB - The aim of this study was to determine whether chemosensitive ventricular afferent activation in humans evokes a diffuse pattern of reflex vasodilation involving the skeletal muscle circulation of all the extremities or a highly specified pattern of vasodilation that is limited to the rather small vascular bed of the forearm. In 10 patients with innervated ventricles and 7 patients with denervated ventricles resulting from heart transplantation, we performed simultaneous plethysmographic recordings of blood flow in the forearm and calf during chemosensitive ventricular afferent activation with intracoronary Renografin. In patients with innervated ventricles, intracoronary Renografin evoked directionally opposite vascular responses in the forearm and calf: forearm resistance decreased from 50 +/- 11 to 31 +/- 8 units, whereas calf resistance increased from 42 +/- 7 to 59 +/- 9 units (P < 0.05, calf vs. forearm). Forearm vasodilation was eliminated after heart transplantation, indicating that this is a reflex response caused by ventricular afferents. In contrast, calf vasoconstriction was well preserved despite ventricular deafferentation, indicating that this response is caused by mechanisms other than ventricular afferent activation, possibly the sinoaortic baroreceptors. Taken together, these findings document a remarkable degree of specificity in the effects of cardiac afferent activation on the reflex regulation of regional vasomotor tone in humans. PMID- 8005855 TI - NG-methyl-L-arginine, an inhibitor of nitric oxide formation, reverses IL-2 mediated hypotension in dogs. AB - The effects of NG-methyl-L-arginine (L-NMA), an inhibitor of nitric oxide formation, were studied in dogs treated with interleukin-2 (IL-2). The administration of IL-2 to dogs resulted in hypotension within 3 days of treatment. The development of hypotension correlated with accumulation in the serum of nitrate, which is a stable breakdown product of nitric oxide. Administration of L-NMA decreased serum nitrate levels and increased the mean arterial pressure. The antihypotensive effect was dose dependent with a maximum effect observed at a dose of 20 mg/kg. Administration of a continuous infusion of L-NMA (5 mg.kg-1.h-1) maintained the mean arterial pressure for 48 h with concurrent administration of IL-2. Evaluation of IL-2-induced lymphokine activated killer cell proliferation and tumoricidal activity toward a canine glioblastoma target cell line was unaffected by L-NMA. These studies imply that L NMA may effectively ameliorate the dose-limiting hypotension associated with administration of IL-2 without adversely affecting the antitumor effects. PMID- 8005857 TI - Catecholamine and blood lactate responses to incremental rowing and running exercise. AB - Ten collegiate rowers performed discontinuous incremental exercise to their tolerable limit on two occasions: once on a rowing ergometer and once on a treadmill. Ventilation and pulmonary gas exchange were monitored continuously, and blood was sampled from a venous catheter located in the back of the hand or forearm for determination of blood lactate ([La]) and plasma epinephrine ([Epi]) and norepinephrine ([NE]) concentrations. Thresholds for lactate (LT), epinephrine (Epi-T), and norepinephrine (NE-T) were determined for each subject under each condition and defined as breakpoints when plotted as a function of O2 uptake (VO2). For running, LT (3.76 +/- 0.18 l/min) was lower (P < 0.05) than Epi T (4.35 +/- 0.14 l/min) and NE-T (4.04 +/- 0.19 l/min). For rowing, LT (3.35 +/- 0.16 l/min) was lower (P < 0.05) than Epi-T (3.72 +/- 0.22 l/min) and NE-T (3.70 +/- 0.18 l/min) and was lower (P < 0.05) than LT for running. Within each mode of exercise, Epi-T and NE-T did not differ. Because LT occurred at a significantly lower VO2 than either Epi-T or NE-T, we conclude that catecholamine thresholds, per se, were not the cause of LT. However, for both modes of exercise LT occurred at a plasma [Epi] of approximately 200-250 pg/ml (rowing, 221 +/- 48 pg/ml; running, 245 +/- 45 pg/ml); these concentrations are consistent with the plasma [Epi] reported necessary for eliciting increments in blood [La] during Epi infusion at rest. Plasma [NE] at LT differed significantly between modes (rowing, 820 +/- 127 pg/ml; running, 1,712 +/- 217 pg/ml).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8005856 TI - Role of N-methyl-D-aspartate receptors in the pontine pneumotaxic mechanism in the cat. AB - Systemic injection of MK-801, an N-methyl-D-aspartate (NMDA) receptor-associated channel blocker, induces an apneusis in vagotomized cats similar to that produced by pontine respiratory group (PRG) lesions, suggesting the possible involvement of NMDA receptors in the pontine pneumotaxic mechanism. Previous results from our laboratory indicate that the efferent limb of the pontine pneumotaxic mechanism is unlikely to require NMDA receptor-mediated neurotransmission. Therefore, the present study examined the potential involvement of PRG NMDA receptors in the pontine pneumotaxic mechanism. Experiments were conducted in decerebrate, paralyzed, and ventilated adult cats. The effects on inspiratory time (TI) of MK 801 microinjection into PRG were tested in 12 cats. Pressure microinjection of MK 801 (15 mM, 80-3,000 nl) significantly prolonged TI in all animals when lung inflation was withheld. TI progressively increased in most animals for > or = 30 min. After this period, partial recovery of the effect occurred in eight cats as TI shortened toward predrug levels. In three animals, microinjection of MK-801 induced a complete apneusis in the absence of lung inflation from which there was no detectable recovery. Microinjections into regions approximately 2 mm distant from PRG produced little or no effect. These results provide evidence that NMDA receptors located in the region of PRG play an important functional role in the control of the breathing cycle. PMID- 8005858 TI - Ontogeny of dry gas hyperpnea-induced bronchoconstriction in guinea pigs. AB - Adolescent guinea pigs (AGPs) demonstrate dry gas hyperpnea-induced bronchoconstriction (HIB) that shares key features with HIB in humans with asthma. The airways of immature animals exhibit enhanced reactivity to diverse types of stimulation. We tested whether dry gas HIB is also increased in newborn guinea pigs (NGPs). We quantified HIB as the fractional increase of respiratory system resistance (Rrs) over baseline (BL) in five 4- to 7-day-old NGPs after 10 min of hyperpnea, as well as changes in Rrs elicited by intravenous methacholine or capsaicin, and compared these responses with those of AGPs. During hyperpnea, analogous stimuli were delivered by mechanically imposing hyperpnea at 3.0, 4.5, and 6.0 times quiet eucapnic minute ventilation (VE). In AGPs, hyperpnea caused significant bronchoconstriction that increased with VE; peak fractional increase of Rrs was 7.6 +/- 2.0 times BL. In contrast, hyperpnea caused insignificant bronchoconstriction in NGPs (1.4 +/- 0.2 times BL after the largest VE; P < 0.05 vs. AGP). Responses elicited by methacholine (10(-10)-10(-7) mol/kg) or capsaicin (0.01-10.0 microgram/kg) were similar in NGPs and AGPs. In AGPs, hyperpnea suppressed HIB until posthyperpnea. To determine whether the reduced HIB of NGPs was caused by enhanced suppression, NGPs and AGPs were administered acetylcholine (10(-10)-10(-7) mol/kg i.v.) during BL eucapnic ventilation and during eucapnic hyperpnea with warm humidified gas. Responses to acetylcholine were suppressed in AGPs and NGPs to a similar degree. We conclude that HIB is markedly diminished shortly after birth in guinea pigs and that it increases substantially during maturation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8005859 TI - Evaporation-induced changes in airway surface liquid on an isolated guinea pig trachea. AB - An isolated preparation of the guinea pig trachea was developed. The trachea was exposed serosally to Krebs-Henseleit solution and mucosally to tidal airflow, designed to mimic conditions in vivo. The preparation establishes stable layers of airway surface liquid (ASL). Typical depth, transepithelial potential differences, and sodium activity are 200 microns, -3 mV, and 125 mM, respectively (approximate sodium concn 170 mM). When exposed to air with a vapor pressure deficit (VPD), evaporation of water occurs from ASL, ASL depth decreases, and the concentration of sodium ions in ASL increases. The water content of air passing over the trachea also increases. This measurement is compared with measurements of the change in volume of ASL, based on depth changes, to yield estimates of net water transport (NWT). Measurements of changes in the sodium content of ASL allow for the calculation of net sodium transport by the trachea. Evaporation rate, changes in the volume of ASL, NWT, and net sodium transport are all influenced by VPD. The results suggest that evaporation from ASL increases its sodium concentration (and osmotic pressure) and increases osmotically driven NWT to replace water lost. Evaporation-induced increases in the sodium concentration appear to be limited by enhanced sodium uptake at high VPD. PMID- 8005860 TI - Sex as a determining factor in the effect of exercise on in vivo autoimmune response adjuvant arthritis. AB - The present study was conducted to examine the effect of physical exercise on the development of adjuvant arthritis (AA), an animal model of the human rheumatoid arthritis, which is a T-cell-dependent autoimmune response. AA was inducted on day 0 in 8-wk-old Lewis rats of both sexes. Between postinjection days 1 and 12, two groups of rats (male and female) were trained on a treadmill every day (45 120 min/day and 15-30 m/min) before the onset of arthritic disease. Trained female (n = 27) and male (n = 22) rats and control female (n = 29) and male (n = 17) rats were observed every 2 days for the following clinical signs of AA: number of arthritic joints (swelling and redness), paw thickness, and weight gain during the disease. The results show that the incidence of arthritis (% of arthritic rats) was significantly higher in trained female rats (74%; P < 0.03) and significantly lower in trained male rats (27%; P < 0.05) compared with control rats of both sexes (female, 45%; male, 59%). There was no difference in the severity and development of the disease between trained rats and control rats of both sexes (P > 0.05). The present study indicates that the effect of exercise on the incidence of AA, an in vivo autoimmune response, depends on the sex of the animal. PMID- 8005861 TI - Human lung impedance from spontaneous breathing frequencies to 32 Hz. AB - Lung impedance (ZL) was measured from 0.1875 to 32 Hz in spontaneously breathing healthy subjects by spectral analysis of the pressure and flow signals generated simultaneously by the muscular generator of breathing and by a forced oscillation system. This method did not require cooperation from the subject to perform panting or special ventilatory maneuvers and therefore allowed us to analyze the frequency dependence of lung resistance, reactance, and elastance (-2 pi.frequency.reactance) at the physiological conditions of normal breathing. Resistance and elastance parameters were also computed by multiple linear regression of the time-domain pressure and flow data on a simple resistance elastance model. Resistances and elastances computed at the breathing frequency by spectral analysis and by multiple linear regression were similar (nonsignificant differences < 4 and 10%, respectively). The results obtained when comparing ZL from the breathing component (0.1875-0.75 Hz) of the recorded signals and from the forced oscillation component (2-32 Hz) were fairly consistent. ZL (0.1875-10 Hz) was interpreted in terms of a model consisting of an airway compartment, including a resistance and an inertance, in series with a viscoelastic tissue compartment (J. Hildebrandt. J. Appl. Physiol. 28: 365-372, 1970) characterized by two parameters. The model analysis provided parameter values (resistance 2.49 +/- 0.58 hPa.l-1.s, inertance 1.70 +/- 0.29 Pa.l-1.s2, Hildebrandt parameters 4.87 +/- 2.28 and 0.73 +/- 0.99 hPa/l) consistent with the hypothesis that lung tissue in healthy humans during spontaneous breathing behaves as a viscoelastic structure with a hysteresivity of approximately 0.10. PMID- 8005862 TI - Effect of endurance training on atrial natriuretic peptide gene expression in normal and hypertrophied hearts. AB - We studied the effects of physical endurance training on atrial natriuretic peptide (ANP) gene expression in beagle dogs, Wistar rats, and spontaneously hypertensive rats (SHR). The dogs underwent a gradually increased running training up to 40 km/day on a treadmill for 55 wk while the nontrained sibling control dogs were kept in their cages throughout the study. Endurance training caused a significant 13% (P < 0.05) increase in ventricular hypertrophy but did not change plasma immunoreactive (ir)-ANP levels at rest or ventricular ANP mRNA or irANP levels. When normotensive Wistar rats ran up to 2,200 m/day for 8 wk, no significant change was seen in ventricular hypertrophy or in plasma or ventricular irANP levels at rest compared with nontrained controls. However, endurance training caused a 2.2-fold increase in epicardial ANP mRNA levels (P < 0.05). In the SHR strain, running training up to 900 m/day for 31 wk increased ventricular hypertrophy of trained SHR by 7% (P < 0.01) and caused a concomitant 1.6- to 1.7-fold elevation in ventricular irANP and ANP mRNA levels (P < 0.01 0.001) compared with nontrained SHR. In contrast, changes in atrial ANP mRNA or irANP levels in response to training were small in all three protocols. This study shows that in the normal heart induction of ANP synthesis by endurance training is not associated with ventricular hypertrophy. Moreover, the common stimulus for ventricular ANP synthesis induced by both chronic pressure overload and physical training may be mechanical stretching of cardiac myocytes, because endurance training further stimulated ANP synthesis in hypertrophied ventricles in SHR. PMID- 8005864 TI - Interrelationships between regional blood flow, blood volume, and ventilation in supine humans. AB - Positron emission tomography was used to measure alveolar gas volume, pulmonary blood volume (VB), regional alveolar ventilation (VA), and the regional ventilation-to-perfusion ratio (VA/Q) in a transaxial slice at midheart level in eight supine subjects and one prone normal subject during quiet breathing. These relationships allow regional blood flow (Q) to be calculated as VA/(VA/Q). No significant differences between right and left lung were found. Within the volume studied, which excluded the peripheral 2 cm of the lung, there was an exponential increase in Q by 11%/cm from 1.2 ml.min-1.cm-3 in the upper (ventral) to 3.5 ml.min-1.cm-3 in the lower (dorsal) lung regions, explaining 61% of the total variation within groups, whereas the horizontal gradient only explained 7% (right lung; supine subjects). Similar gravitational gradients were found in the single prone subject. VA and Q were well matched except at the dorsal lung thoracic border where low values of VA/Q due to a reduction in ventilation were occasionally found even in these normal subjects. VB and Q were reasonably well matched, implying that variations in vascular transit time due to gravity are kept to a minimum. The coefficient of local variation of peripheral vascular transit times (VB/Q) (33%) was, therefore, less than would have been expected if VB and Q were uncorrelated (57%). PMID- 8005863 TI - Relationships between regional ventilation and vascular and extravascular volume in supine humans. AB - With the use of positron emission tomography, alveolar ventilation (VA), lung density, and pulmonary blood volume (VB) were measured regionally in eight nonsmokers in the supine posture and one nonsmoker in the prone posture during quiet breathing in a transaxial thoracic section at midheart level. Regional values of alveolar volume (VA) and extravascular tissue volume (VEV) were derived from the inherent relationships between different compartments in the lung. Ratios proportional to gas volume (VA/VEV) and ventilation (VA/VEV) per alveolar unit, respectively, were calculated. No differences between right and left lung were found. Variations in the vertical direction could explain approximately 65% of the total within-group variation in VA, VB, and ln (VA), whereas the corresponding value for horizontal variation was only 3-9% (right lung, supine subjects). Similar gravitational gradients were found in the single prone subject. There was a significant linear correlation between VA and ln (VA). When VA and VA are related to a given number of alveolar units (VEV), the data are consistent with a linear relationship between VA/VEV and VA/VEV, indicating that ventilation might be explained by the elastic properties of lung tissue according to Salazar and Knowles (J. Appl. Physiol. 19: 97-104, 1964). Regional VB was closely associated with the gradient of regional alveolar volume (VA/VEV) (by virtue of weight of blood and competition for space) and therefore, indirectly, closely associated with the vertical gradient of ventilation. PMID- 8005865 TI - Effect of chronic acetazolamide administration on gas exchange and acid-base control after maximal exercise. AB - The interaction between systems regulating acid-base balance (i.e., CO2, strong ions, week acids) was studied in six subjects for 10 min after 30 s of maximal isokinetic cycling during control conditions (CON) and after 3 days of chronic acetazolamide (ChACZ) administration (500 mg/8 h po) to inhibit carbonic anhydrase (CA). Gas exchange was measured; arterial and venous forearm blood was sampled for acid-base variables. Muscle power output was similar in ChACZ and CON, but peak O2 intake was lower in ChACZ; peak CO2 output was also lower in ChACZ (2,207 +/- 220 ml/min) than in CON (3,238 +/- 87 ml/min). Arterial PCO2 was lower at rest, and its fall after exercise was delayed in ChACZ. In ChACZ there was a higher arterial [Na+] and lower arterial [lactate-] ([La-]) accompanied by lower arterial [K+] and higher arterial [Cl-] during the first part of recovery, resulting in a higher arterial plasma strong ion difference (sigma [cations] - sigma [anions]). Venoarterial (v-a) differences across the forearm showed a similar uptake of Na+, K+, Cl-, and La- in ChACZ and CON. Arterial [H+] was higher and [HCO3-] was lower in ChACZ. Compared with CON, v-a [H+] was similar and v-a [HCO3-] was lower in ChACZ. Chronic CA inhibition impaired the efflux of CO2 from inactive muscle and its excretion by the lungs and also influenced the equilibration of strong ions.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8005866 TI - Myosin and actin filament lengths in diaphragms from emphysematous hamsters. AB - In vitro studies of the diaphragm from emphysematous animals have, in some instances, shown an alteration in its sarcomere length-tension relationship and a decreased maximal specific tension. To our knowledge, it has never been determined whether such functional changes may be indicative of ultrastructural adaptations, e.g., changes in filament lengths and thus cross-bridge number. To address this, we compared filament lengths in diaphragms from hamsters in which emphysema was induced by endotracheal instillation of elastase (E) 5 mo before the hamsters were killed with those from control hamsters (C; saline instillation). Diaphragms were then fixed by vascular perfusion with buffered glutaraldehyde in situ at airway pressures set to approximate the physiological range of lung volumes from residual volume (RV) to total lung capacity (TLC). Ultrathin sections (50-70 nm) were taken parallel to the muscle fiber axis and examined by electron microscopy (x33,000). Sarcomere and filament length measurements were calibrated using an actin periodicity of 39 nm and an M-band width of 86 nm to correct for dimensional changes during preparation. Emphysema increased the change in lung volume from -20 to +25 cmH2O airway pressure (from RV to TLC) by approximately 88%, and the displacement volume of excised lung at 0 cmH2O airway pressure was increased by approximately 138% on average. Neither myosin (C = 1.592 +/- 0.027; E = 1.572 +/- 0.035 micron; P = 0.72) nor actin (C = 1.210 +/- 0.035; E = 1.221 +/- 0.014 micron; P = 0.76) filament lengths were affected by emphysema. Thus, filament length changes do not underlie the diaphragm functional adaptations observed previously in emphysema. PMID- 8005867 TI - Assessment of injury in transplanted and nontransplanted lungs after 6 h of cold storage with glutathione. AB - Single-lung transplantation after 3 h of hypothermic storage produces bilateral lung injury [pulmonary reimplantation response (PRR)]. We hypothesized that glutathione (GSH) hypothermic storage would protect both lungs from PRR for extended preservation times and that differences in injury and protection would be realized between the graft and the nontransplanted lung. Mongrel dogs underwent left single-lung autotransplantation after preservation for 5-6 h in Euro-Collins (EC) solution, EC plus exogenous GSH (EC+GSH), or Viaspan (VIA) at 4 degrees C. Lung injury was measured in both lungs after 1 h of reperfusion. EC dogs demonstrated significant increases in lung edema, lipid peroxidation, and alveolar neutrophil recruitment in the lung graft and to a less extent in the nontransplanted right lung compared with control dogs (P < 0.05). Edema, lipid peroxidation, and alveolar neutrophils were significantly reduced in both lungs from EC+GSH and VIA dogs compared with lungs from EC dogs (P < 0.05). An increase in large-pore permeability was measured in the lung graft from EC dogs compared with all other lungs. Bronchoalveolar lavage fluid lactate dehydrogenase and total protein concentrations were elevated in both lungs from all three groups of tranplanted dogs compared with those of control dogs (P < 0.05). These data suggest that GSH-containing solutions attenuate the PRR after 6 h of ischemic hypothermic storage but that the protection is incomplete. Mechanisms of injury affecting the lung graft during the PRR appear to differ from those affecting the nontransplanted lung. PMID- 8005868 TI - Effect of acceleration on the chest wall. AB - The gravitational force on the rib cage has been found to be an expiratory force of approximately 8 cmH2O. The gravitational force on the abdomen is an inspiratory force of the same magnitude. Because the compliance of the rib cage is greater than the compliance of the abdomen, it follows that gravity has a net expiratory effect on lung volume and that upward accelerations augmenting the gravitational force would have an additional expiratory effect. This conclusion is contrary to observations that functional residual capacity increases during headward accelerations in centrifuges and during intervals of upward acceleration in airplanes. We report the results of two studies of the effects of accelerations that are smaller in magnitude and of shorter duration than those studied in centrifuges and airplanes. The first was an experimental study of the effect of acceleration in an elevator. In subjects who relaxed against an occluded airway, airway pressure increased during upward accelerations and decreased during downward accelerations. The second was the modeling and analysis of the effects of the accelerations that occur during walking. The analysis predicted an initial expiratory response to the acceleration spike that occurs during footfall. The prediction agreed with data in the literature on the respiratory effect of walking. In both of these studies upward accelerations had an expiratory effect. PMID- 8005869 TI - Skeletal muscle adaptations during early phase of heavy-resistance training in men and women. AB - An 8-wk progressive resistance training program for the lower extremity was performed twice a week to investigate the time course for skeletal muscle adaptations in men and women. Maximal dynamic strength was tested biweekly. Muscle biopsies were extracted at the beginning and every 2 wk of the study from resistance-trained and from nontrained (control) subjects. The muscle samples were analyzed for fiber type composition, cross-sectional area, and myosin heavy chain content. In addition, fasting blood samples were measured for resting serum levels of testosterone, cortisol, and growth hormone. With the exception of the leg press for women (after 2 wk of training) and leg extension for men (after 6 wk of training), absolute and relative maximal dynamic strength was significantly increased after 4 wk of training for all three exercises (squat, leg press, and leg extension) in both sexes. Resistance training also caused a significant decrease in the percentage of type IIb fibers after 2 wk in women and 4 wk in men, an increase in the resting levels of serum testosterone after 4 wk in men, and a decrease in cortisol after 6 wk in men. No significant changes occurred over time for any of the other measured parameters for either sex. These data suggest that skeletal muscle adaptations that may contribute to strength gains of the lower extremity are similar for men and women during the early phase of resistance training and, with the exception of changes in the fast fiber type composition, that they occur gradually. PMID- 8005871 TI - Thyroarytenoid muscle activity during hypocapnic central apneas in awake nonsedated lambs. AB - In this study, we examined whether the glottis is open or closed during central apnea and the effect of arterial PO2 (PaO2) on this control. We hyperventilated nine 11- to 30-day-old awake nonsedated lambs via a tracheostomy for 1 min to induce central apnea. Four gas mixtures (8, 15, 21, and 30% O2) were used. At the end of the hyperventilation period, the lambs were allowed to breathe spontaneously through intact upper airways. Using a pneumotachograph attached to a face mask, we measured airflow, and we continuously recorded electromyographic (EMG) activity of the thyroarytenoid (TA), the main glottic adductor muscle. We also studied the lateral cricoarytenoid muscle (LCA, laryngeal adductor), the posterior cricoarytenoid muscle (PCA, laryngeal abductor), the cricothyroid muscle (CT), and the diaphragm. We found that hyperventilation consistently induced hypocapnic central apnea in all nine lambs in hyperoxic conditions [30% inspiratory fraction of O2 (FIO2)], in eight of nine lambs in normoxia or mild hypoxia (15 and 21% FIO2), and in four of seven lambs in hypoxia (8% FIO2). During baseline room air breathing, there was no glottic adductor muscle expiratory EMG activity or expiratory airflow braking. Continuous TA EMG activity began early during hyperventilation and continued throughout the central apnea, regardless of PaO2. The first subsequent breathing efforts were marked by expiratory flow braking and expiratory activity of the TA. The LCA and the TA demonstrated the same EMG activity pattern.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8005870 TI - Hypoxic vasodilation does not require nitric oxide (EDRF/NO) synthesis. AB - Our question was whether inhibition of nitric oxide [endothelium-derived relaxing factor (EDRF)/NO] production in an in situ vascularly isolated but innervated canine hindlimb would prevent hypoxic vasodilation or interfere with O2 extraction during ischemic (IH) or hypoxic hypoxia (HH). After a control period, we gave NG-nitro-L-arginine methyl ester (L-NAME, 20 mg/kg i.v.) to two of four groups of six dogs before a 30-min period of IH or HH. In IH, arterial inflow from a pump-membrane oxygenator system was lowered from 65 to 35 ml.min-1.kg-1 with PO2 maintained at approximately 110 Torr. In HH, PO2 was lowered from 107 to 28 Torr with flow at 78 ml.min-1.kg-1. Total O2 delivery was lowered to approximately 5 ml.min-1.kg-1 in all groups during hypoxia. Hindlimb vascular resistance (LVR) increased from 1.11 +/- 0.09 to 2.21 +/- 0.25 peripheral resistance units (PRU; P < 0.05) after L-NAME infusion and hindlimb O2 uptake increased from 3.9 +/- 0.2 to 4.5 +/- 0.3 ml.min-1.kg-1 (P < 0.05). In controls, LVR decreased from 1.10 +/- 0.06 to 0.63 +/- 0.04 PRU with HH (P < 0.05) and from 1.03 +/- 0.06 to 0.82 +/- 0.02 PRU (P = NS) with IH. In L-NAME-treated dogs, LVR decreased from 2.38 +/- 0.37 to 1.07 +/- 0.13 PRU with HH (P < 0.05) and from 2.04 +/- 0.29 to 1.41 +/- 0.13 PRU (P = NS) with IH. There were no differences in O2 extraction ratio (0.72) or in O2 uptake between groups during hypoxia.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8005873 TI - Release of creatine kinase and prostaglandin E2 from regenerating skeletal muscle fibers. AB - To study the effect of regeneration on the release of creatine kinase (CK) and prostaglandin E2 from muscle, extensor digitorum longus muscles of mice were injected with 50 microliters of BaCl2 solution in saline (1.2% wt/vol). Injected muscles showed almost complete degeneration at 3 days postinjection but had regenerated to approximately the same fiber cross-sectional area as contralateral control muscles by 12 days postinjection. These muscles released reduced amounts of intracellular CK compared with contralateral control muscles in response to excessive isometric contractile activity or treatment with the calcium ionophore A-23187 (20 microM) in vitro. However, regenerating muscles contained a lower total CK activity than contralateral control muscles, which accounted for the reduced CK efflux after experimental damage. Regenerating muscles released an increased amount of prostaglandin E2 compared with control muscles after both damaging stimuli. We conclude that regenerated muscles show no reduced susceptibility to contraction-induced damage (as assessed by CK release) but show an elevated release of prostaglandin E2 in response to contractile activity or an increase in intracellular calcium. PMID- 8005872 TI - Exercise-induced changes in plasma catecholamines and neuropeptide Y: relation to age and sampling times. AB - Plasma norepinephrine (NE), epinephrine (E), and neuropeptide Y (NPY) were evaluated in seven young (median age 29 yr, range 21-31) and seven elderly (median age 61 yr, range 51-72) healthy subjects. They were all nonsmokers and had never smoked. Basal values and the initial increase in plasma NE and E during exercise at 75% of maximal work load were identical in the two groups. After 5 min of exercise at this load, plasma NE and E remained constant in the elderly but were still increasing in the young subjects. Plasma NE and E increased to significantly higher values after 15 min in the young subjects: 1.68 +/- 0.18 vs. 0.92 +/- 0.11 ng/ml (NE) and 0.136 +/- 0.012 vs. 0.061 +/- 0.013 ng/ml (E). Basal plasma NPY was highest at rest and increased only during exercise in the young subjects. Our results demonstrate that in nonsmokers aging is not associated with increased plasma NE levels. The blood pressure response to exercise was the same in both groups, suggesting that the increase in the sympathetic activity was adequate in the elderly. Alternatively, the higher increase in sympathetic activity in the young subjects may be attributed to their higher work capacity. PMID- 8005874 TI - Effects of hypercapnia on metabolism, temperature, and ventilation during heat and fever. AB - We wished to determine whether 1) acute hypercapnia in cats changes metabolic heat production to affect temperature regulation and 2) heat exposure and fever affect the normal response. The effects of breathing 4% CO2 on O2 consumption (VO2), rectal temperature (Tre), and ventilation (V) were measured in five conscious resting cats. Cats were exposed to a normal (24-27 degrees C) chamber temperature (Ta) and a warm (33-34 degrees C) chamber Ta. Fever was produced by intravenous injection of Escherichia coli endotoxin (0.02 microgram/kg) at a normal Ta. In normothermic cats, hypercapnia decreased VO2 by approximately 40%, despite an increased V (approximately 100%), but Tre decreased only transiently and slightly compared with studies in which air was breathed throughout. During heat studies, average V was elevated but VO2 was markedly lower than at the normal Ta; Tre gradually increased. Hypercapnia combined with heat did not cause additional increases in VO2, nor did it cause a decrease in VO2, as at a normal Ta; however, the rate of rise of Tre during heat was slowed by hypercapnia. During febrigenesis, hypercapnia prevented the transient increase in VO2 observed when air was breathed and delayed the rate of rise in Tre. As Tre was falling in fever, hypercapnia depressed VO2 but did not affect Tre compared with fever studies in which air was breathed. Unlike heat exposure, hypercapnia had a further additive stimulatory effect on the increase in V at the onset of fever, and it increased V during the falling phase of fever when V had returned to control levels.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8005875 TI - Clinical tests explain blunted cortisol responsiveness but not mild hypercortisolism in amenorrheic runners. AB - To investigate mechanisms of blunted adrenocortical responsiveness to exercise and mild hypercortisolism in amenorrheic runners, adrenocorticotropic hormone [ACTH-(1-24) 0.25 mg Cortrosyn] stimulation tests were performed in the presence and absence of overnight dexamethasone (1 mg) suppression (DX and NDX condition, respectively) in six eumenorrheic sedentary women (ES), nine eumenorrheic runners (ER), and nine amenorrheic runners (AR). Before the NDX stimulation test, plasma cortisol was higher (P < 0.001) in AR than in ER and ES. The cortisol response to the NDX stimulation test was blunted (P < 0.001) in AR but reached similar (P > 0.7) peak levels in all groups. Dexamethasone suppressed (P < 0.001) cortisol to similar (P > 0.5) levels (approximately 20 nmol/l) in all groups. In AR, cortisol responses to the DX test were larger (P < 0.03) than to the NDX test and similar (P > 0.6) in the three groups, again reaching comparable (P > 0.8) peak levels. The blunted cortisol response to stimulation in AR in the presence of their mild hypercortisolism appears to be due to a normal limitation in maximal adrenal secretory capacity. Extrapituitary modulators of adrenal responsiveness to ACTH may explain the mild hypercortisolism observed in AR, but limitations of these tests prevent a central negative-feedback defect or an intrinsic adrenal abnormality from being excluded until results of additional studies with even lower doses of dexamethasone and submaximal doses of ACTH-(1-24) are available. PMID- 8005876 TI - Behavioral effects of carbon monoxide: meta analyses and extrapolations. AB - In the absence of reliable data, this work was performed to estimate the dose effects function of carboxyhemoglobin (HbCO) on behavior in humans. Meta analysis is the quantitative analysis of the combined findings of a number of research reports. By meta analysis, an HbCO-behavior dose-effects function was estimated for rats and corrected for effects of hypothermia (which accompanies acute HbCO increases in rats but not in humans). By use of pulmonary function models and blood gas equations, equivalent HbCO values were calculated for data in the literature on hypoxic hypoxia and behavior. Another meta analysis was performed to fit a dose-effects function to the equivalent HbCO data and to correct for the behavioral effects of hypocapnia (which usually occurs during hypoxic hypoxia but not with HbCO elevation). The two extrapolations agreed closely and indicated that, for healthy sedentary persons, 18-25% HbCO would be required to produce a 10% decrement in behavior. Confidence intervals are computed to characterize the uncertainty. Frequent reports of lower-level effects are discussed. PMID- 8005877 TI - Testing the metabolic hypothesis of O2 chemoreception in the cat carotid body in vitro. AB - It is known that oligomycin reduces the oxidative phosphorylation high-energy state or high-energy intermediates by inhibiting the formation of ATP without directly inhibiting electron transport, whereas metabolic uncouplers dissipate the high-energy state without net production of ATP. The metabolic hypothesis for O2 chemoreception in the carotid body (CB) predicts that 1) oligomycin should diminish O2 consumption and attenuate O2 chemoreception and 2) uncouplers should reverse the effect of oligomycin by increasing O2 consumption without restoring O2 chemoreception. These predictions were tested by simultaneously measuring CB chemosensory discharge from the sinus nerve and the rate of tissue O2 disappearance (dPO2/dt) during interruption of perfusate flow in perfused superfused cat CB preparations (n = 9). O2 consumption was calculated from dPO2/dt. Flow-interruption responses were measured before and after oligomycin (1 microgram bolus) and subsequently after dinitrophenol (50 microM). Chemosensory responses to bolus injections of hypercapnic Tyrode solution, cyanide, or nicotine were also tested periodically. Oligomycin diminished dPO2/dt from -2.67 +/- 0.30 to -2.02 +/- 0.19 (SE) Torr/s (P < 0.004, paired t test) and reduced the maximal sensory response from 196 +/- 43 to 124 +/- 12 impulses/s (P < 0.002, paired t test) while augmenting the initial response to CO2. Dinitrophenol reversed the metabolic depressant effect of oligomycin but further suppressed the chemosensory response. These results confirm the above predictions and strengthen the metabolic hypothesis for O2 chemoreception in the CB. PMID- 8005878 TI - Effects of inhaled NO and inhibition of endogenous NO synthesis in oxidant induced acute lung injury. AB - Inhaled nitric oxide (NO) decreases pulmonary arterial pressure (Ppa) and improves oxygenation in the adult respiratory distress syndrome. Endogenous NO can modulate the development of acute tissue injury. We investigated the effects of inhaled NO and of inhibition of endogenous NO synthase in oxidant-induced acute lung injury in the isolated buffer-perfused rabbit lung. A rapid (45 min) and a more gradual (3 h) model of oxidant-induced acute lung injury were developed using the production of superoxide free radicals from the reaction of purine with low and high doses of xanthine oxidase, respectively. The effects of rapid injury included increases in Ppa, precapillary pulmonary vascular resistance, capillary filtration coefficient (Kfc), and lung weight. In the gradual-injury model, only lung weight and Kfc increased. Pretreatment with inhaled NO (90-120 ppm) prevented the rise in Ppa and precapillary pulmonary vascular resistance in the rapid-injury model and prevented elevation of Kfc in the gradual-injury model. Pretreatment with an inhibitor of endogenous NO synthase (NG-nitro-L-arginine methyl ester) resulted in increased pulmonary capillary pressure and postcapillary pulmonary vascular resistance in the rapid injury model and increased peak Ppa, pulmonary capillary pressure, and pulmonary vascular resistance in the gradual-injury model. These data suggest that in oxidant-induced acute lung injury 1) inhaled NO may attenuate increases in capillary permeability and 2) endogenous NO may function as a modulator of pulmonary vascular tone without affecting capillary permeability. PMID- 8005879 TI - Diaphragm and lung afferents contribute to inspiratory load compensation in awake ponies. AB - We determined the effect of pulmonary vagal (hilar nerve) denervation (HND) and diaphragm deafferentation (DD) on inspiratory load compensation. We studied awake intact (I; n = 10), DD (n = 5), HND (n = 4), and DD+HND (n = 7) ponies at rest and during mild (1.8 mph, 5% grade) and moderate (1.8 mph, 15% grade) treadmill exercise before, during, and after resistance of the inspiratory circuit was increased from approximately 1.5 to approximately 20 cmH2O.l-1.s. During the first loaded breath in I ponies at rest, inspiratory time (TI) increased, expiratory time decreased, and inspiratory drive increased. There were minimal changes after the first breath, and inspiratory minute ventilation (VI) and arterial PCO2 did not change (P > 0.10) from control values. On the first loaded breath during exercise, TI increased but inspiratory drive either did not change or decreased from control values. TI and drive increased after the first breath, but the increases were insufficient to maintain VI and arterial PCO2 at control levels. First-breath load compensation remained after DD, HND, and DD+HND, but after DD+HND tidal volume and VI were compensated 5-10% less (P < 0.05) than in I ponies. In all groups inspiratory drive, tidal volume, and VI were markedly augmented on the first breath after loading was terminated with a gradual return toward control. We conclude that diaphragm and pulmonary afferents contribute to but are not essential for inspiratory load compensation in awake ponies. PMID- 8005880 TI - Central angiotensin II stimulation of ovine fetal swallowing. AB - In the late-gestation ovine fetus, spontaneous swallowing occurs primarily during fetal low-voltage electrocortical (ECoG) activity in association with fetal breathing movements. Fetal swallowing activity may be stimulated in response to systemic or carotid plasma hyperosmolality, although not to increased plasma angiotensin II (ANG II) levels. In view of the potent dipsogenic effects of central, but not peripheral, ANG II in adult sheep, the present study investigated the effect of intracerebroventricular (ICV) ANG II on fetal swallowing activity. Six ovine fetuses (127 +/- 1 days) were chronically prepared with electromyogram and cortical electrodes and with vascular and lateral ventricle catheters. After a 2-h control period, fetuses received ICV injections of artificial cerebrospinal fluid and increasing concentrations of ANG II (0.1, 1.0, 10, 100, and 500 ng/kg). Fetal ECoG activity did not change, although fetal swallowing activity significantly increased in response to the 100- and 500- ng/kg ANG II doses (1.20 +/- 0.14 to 3.34 +/- 0.59 and 3.46 +/- 0.81 swallows/min of low-voltage ECoG, respectively). In response to the highest ANG II dose, fetal plasma arginine vasopressin levels significantly increased (5.7 +/- 1.2 to 17.2 +/- 4.6 pg/ml). ICV ANG II stimulation of fetal swallowing and arginine vasopressin secretion demonstrates that central ANG II dipsogenic mechanisms are intact by 0.9 of ovine gestation. PMID- 8005881 TI - Neuropeptide Y release from human heart is enhanced during prolonged exercise in hypoxia. AB - To evaluate the effect of hypoxemia on cardiac release of neuropeptide Y-like immunoreactivity (NPY-LI) and norepinephrine (NE), arterial and coronary sinus blood was sampled and coronary sinus blood flow was measured by thermodilution in nine healthy volunteers at rest and during supine cycle ergometer exercise while they breathed air and 12% O2, which reduced arterial O2 saturation to approximately 68%. Five subjects started to exercise for 30 min breathing air and continued for 30 min breathing 12% O2; four subjects breathed 12% O2 and air in the reverse order. The load was adjusted to give the same heart rate during O2 and air breathing. No significant cardiac net release of NPY-LI or NE was seen at rest. Exercise induced release of NPY-LI and NE. The net release of NPY-LI was 0.7 +/- 0.4 pmol/min during air breathing (average 12 and 30 min) and 2.8 +/- 0.6 pmol/min during 12% O2 breathing. The difference was not influenced by the order of the breathing periods. The NE coronary sinus-arterial difference was not significantly different between 12% O2 and air breathing, whereas the net release was significantly larger during 12% O2 breathing (0.6 +/- 0.1 vs. 0.4 +/- 0.1 nmol/min). Thus, NPY is released with NE from the heart during exercise. Arterial hypoxemia seems to be an additional stimulus of preferential NPY release. PMID- 8005882 TI - Inhaled nitric oxide partially reverses hypoxic pulmonary vasoconstriction in the dog. AB - Nitric oxide (NO) inhaled during a hypoxia-induced increase in pulmonary vasomotor tone decreases pulmonary arterial pressure (Ppa). We conducted this study to better characterize the hemodynamic effects induced by NO inhalation during hypoxic pulmonary vasoconstriction in 11 anesthetized ventilated dogs. Arterial and venous systemic and pulmonary pressures and aortic flow probe derived cardiac output were recorded, and nitrosylhemoglobin (NO-Hb) and methemoglobin (MetHb) were measured. The effects of 5 min of NO inhalation at 0, 17, 28, 47, and 0 ppm during hyperoxia (inspiratory fraction of O2 = 0.5) and hypoxia (inspiratory fraction of O2 = 0.16) were observed. NO inhalation has no measurable effects during hyperoxia. Hypoxia induced an increase in Ppa that reached plateau levels after 5 min. Exposure to 28 and 47 ppm NO induced an immediate (< 30 s) decrease in Ppa and calculated pulmonary vascular resistance (P < 0.05 each) but did not return either to baseline hyperoxic values. Increasing the concentration of NO to 74 and 145 ppm in two dogs during hypoxia did not induce any further decreases in Ppa. Reversing hypoxia while NO remained at 47 ppm further decreased Ppa and pulmonary vascular resistance to baseline values. NO inhalation did not induce decreases in systemic arterial pressure. MetHb remained low, and NO-Hb was unmeasurable. We concluded that NO inhalation only partially reversed hypoxia-induced increases in pulmonary vasomotor tone in this canine model. These effects are immediate and selective to the pulmonary circulation. PMID- 8005883 TI - Distribution function of transit times in the human pulmonary circulation. AB - The distribution function of pulmonary transit times (fPTT) defines contact time between blood and vascular bed, which affects gas exchange and endothelial metabolic functions. This study was undertaken to assess effects of abnormal pulmonary inflow (PPA) and outflow pressures (PLA) on fPTT. Three groups were studied: five patients with elevated PLA and passive pulmonary hypertension (LVD Ab), eight with normal PLA (LVD-Nl), and six with pulmonary disease and various levels of PPA (PD). Empirical complex exponential functions were convoluted on right and left ventricular indicator-dilution curves to derive fPTT; mean transit time (Mo1), standard deviation (Sm2), and cube root of the third moment about Mo1 (Sm3) were calculated by standard equations. A single linear regression of Sm3 and Sm2 on Mo1 was observed for all patients, regardless of disease process. Inverse relations between Mo1, Sm2, and Sm3 and blood flow were highly significant, but dispersion volumes (DV = Mo1 x flow) were higher in patients with elevated PPA. Significant linear regressions of fPTT parameters on PPA, derived in LVD-Nl and LVD-Ab patients, failed to predict Mo1, Sm2, and Sm3 for the PD group, whereas linear regressions on PLA accurately predicted Mo1, Sm2, and Sm3 in the PD group. Relations between fPTT parameters and PLA were equally well fit by exponential equations in all 19 patients, consistent with an asymptotic pressure-volume relation of distensible vessels. Microvascular pressure (PMV), combining PPA and PLA, was not a better predictor of fPTT parameters in LVD-NL and LVD-Ab patients but provided a slightly closer estimate of relative dispersion and skewness in PD patients.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8005884 TI - Airway reopening pressure in isolated rat lungs. AB - In a previous modeling study, we predicted that the yield pressure for airway reopening (Pyield) should depend on airway fluid surface tension (gamma) and airway radius (R), according to the relationship Pyield = 8.3 gamma/R. To test this prediction, we studied tantalum bronchograms of isolated perfused rat lungs from three rats by using microfocal X-ray imaging. Thirty-two airways with diameters ranging from 300 to 2,400 microns were recorded as the airways were collapsed and reinflated. Airway pressure was reduced transiently to -40 cmH2O to produce airway closure. Airway pressure was then slowly increased from 0 to 25 cmH2O. In each airway, the observed diameter remained constant until a Pyield was reached; at this pressure, airways were seen to "pop" open, allowing clear identification of airway reopening pressure. When Pyield was plotted against diameter at maximum inflation, the experimental data were in approximate agreement with predictions of Pyield made assuming a gamma of 35 dyn/cm. The close correspondence of the measured values with these predictions suggests that surfactant is present in these airways and facilitates airway reopening. PMID- 8005885 TI - Regurgitant volume in aortic regurgitation from a parameter estimation procedure. AB - The regurgitant volume and regurgitant orifice area as well as total peripheral resistance and arterial compliance were estimated in a cardiovascular hydromechanical simulator and in 10 patients with aortic regurgitation. A parameter estimation procedure based on a simple model of the cardiovascular system, Doppler measurements of the regurgitant jet, aortic systolic flow, and systolic and diastolic blood pressures was used. In the cardiovascular simulator the estimated regurgitant orifice area was compared with the size of a hole in the disk of a mechanical aortic valve. In the patients the regurgitant fraction was compared with semiquantitative grading from echocardiography routinely performed in our laboratory. In the hydromechanical simulator, the estimated regurgitant orifice area of 26.5 +/- 3.5 (SD) mm2 (n = 9) was not different from the true value of 24 mm2. In the patients there was a fair relationship between the estimated regurgitant fraction and the semiquantitative grading. The estimated regurgitant orifice areas varied between 1.6 and 31.2 mm2. The estimated mean values of total peripheral resistance and arterial compliance were 1.67 +/- 0.55 mmHg.s.ml-1 and 1.30 +/- 0.42 ml/mmHg, respectively. PMID- 8005886 TI - Circumsinus branch: a convenient source of baro- and chemoreceptor activity in dogs. AB - We found a branch of the carotid sinus nerve in 44 of 48 dogs. We propose that this branch be referred to as the "circumsinus" branch of the carotid sinus nerve. Both chemoreceptor and baroreceptor activity were detected in this branch during electrophysiological recording efforts utilizing classic nerve recording techniques. Its convenient location permits whole nerve or single unit recording without having to transect, dissect, or even expose the carotid sinus nerve. Carotid baroreceptor and chemoreceptor activity can be monitored with most of the carotid bifurcation's neural pathways intact. PMID- 8005887 TI - Noninvasive measurement of forearm blood flow and oxygen consumption by near infrared spectroscopy. AB - We applied near-infrared spectroscopy (NIRS) for the simultaneous measurement of forearm blood flow (FBF) and oxygen consumption (VO2) in the human by inducing a 50-mmHg venous occlusion. Eleven healthy subjects were studied both at rest and after hand exercise during vascular occlusion. FBF was also measured by strain gauge plethysmography. FBF measured by NIRS was 1.9 +/- 0.8 ml.100 ml-1.min-1 at rest and 8.2 +/- 2.9 ml.100 ml-1.min-1 after hand exercise. These values showed a correlation (r = 0.94) with those obtained by the plethysmography. VO2 values were 4.6 +/- 1.3 microM O2 x 100 ml-1.min-1 at rest and 24.9 +/- 11.2 microM O2 x 100 ml-1.min-1 after hand exercise. The scatter of the FBF and VO2 values showed a good correlation between the two variables (r = 0.93). The results demonstrate that NIRS provides the particular advantage of obtaining the contemporary evaluation of blood flow and VO2, allowing correlation of these two variables by a single maneuver without discomfort for the subject. PMID- 8005889 TI - Differential effects of voluntary and involuntary activation on contractile characteristics of two human muscles. AB - To compare the maximal rate of rise of torque (MRRT) of quadriceps femoris and adductor pollicis during voluntary and involuntary contractions, subjects performed voluntary isometric contractions as rapidly as possible over the full range of force-producing capacity. Involuntary contractions were evoked with single shocks and with trains of 10 pulses at 100 Hz at increasing voltages applied directly to the femoral and ulnar nerves. There were linear relationships between MRRT and absolute torque in both muscles during involuntary and voluntary contractions. At the same absolute torque, quadriceps femoris had a higher MRRT than adductor pollicis when both were voluntarily activated (P < 0.05). However, there was no difference in MRRT between these muscles during stimulated contractions. Compared with involuntary tetanic contractions, MRRT during voluntary contractions was the same in quadriceps femoris and was less in adductor pollicis (P < 0.05). These observations suggest that in activating some muscles, such as adductor pollicis, the central nervous system may adopt the strategy of a more gradual excitation to make the contractions more task appropriate. PMID- 8005888 TI - Fura 2 determination of [Ca2+]i in isolated perfused heart using R wave-gated electromechanical shutters. AB - We describe a novel and relatively inexpensive spectrofluorescence system that supplies rapidly alternating wavelengths to either a standard cuvette or an isolated perfused heart. Its use is illustrated by determining changes in cytosolic intracellular Ca2+ concentration ([Ca2+]i) by using the Ca(2+) sensitive fluorescent dye fura 2 in a rabbit heart preparation. The system uses two precision electromechanical shutters (capable of gating with respect to the electrocardiographic R wave for signal averaging) allowing alternate fura 2 excitation wavelengths (340 and 380 nm) without moving optical components and uses a fiber optic for conducting excitation and collecting epifluorescence. Sample recordings tracing the [Ca2+]i transient in an entire cardiac cycle and in capturing specific isolated regions (diastole and systole) of the cycle are presented. Limitations of this low-cost but easily implemented system are discussed. PMID- 8005890 TI - "Natural surfactant and hyperoxic lung injury in primates". PMID- 8005892 TI - Continuing medical education. The quiet revolution. PMID- 8005891 TI - Natural surfactant and hyperoxic lung injury in primates. I. Physiology and biochemistry. AB - Surfactant dysfunction contributes to the pathophysiology of adult respiratory distress syndrome (ARDS), and we hypothesized that surfactant treatment would improve experimental ARDS produced by continuous exposure to hyperoxia. Twelve healthy male baboons (10-15 kg) were anesthetized, paralyzed, and mechanically ventilated with 2.5 cmH2O positive end-expiratory pressure (PEEP) for 96 h. Baboons were divided into three groups: 1) the O2 group (n = 5) received 100% O2, 2) the surfactant group (n = 5) received 100% O2 and aerosolized porcine surfactant, and 3) a control group (n = 2) was ventilated at fractional concentration of inspired O2 of 0.21 for 96 h to control for effects of anesthesia and mechanical ventilation. Hemodynamic parameters were obtained every 12 h, and ventilation-perfusion (VA/Q) distribution was measured daily by multiple inert gas elimination technique. PEEP was increased once or twice daily to 10 cmH2O for 30 min to study its effects on measurements of VA/Q. At the end of experiments, lungs were obtained for biochemical analysis. Prolonged hyperoxia resulted in progressive worsening in VA/Q, hemodynamic deterioration, severe lung edema, and altered surfactant metabolism. Surfactant administration increased disaturated phosphatidylcholine in lavage fluid but did not improve lung edema or gas exchange. In the surfactant group, however, the addition of 10 cmH2O PEEP resulted in a greater degree of shunt reduction than did 2.5 cmH2O PEEP (47 vs. 31% in the O2 group, P < 0.05). We conclude that aerosolized porcine surfactant did not prevent pulmonary O2 injury in baboons, but it potentiated the shunt reducing effect of PEEP. PMID- 8005893 TI - Managed $ and Arkansas hospitals. PMID- 8005894 TI - Mercury contamination in Arkansas gamefish. A public health perspective. PMID- 8005895 TI - Radiological case of the month. Hydronephrosis of right kidney after stent migration. PMID- 8005896 TI - Interviewing prepubertal children about suicidal ideation and behavior. AB - OBJECTIVE: Much of the literature on assessment of suicidal children has focused on identifying risk factors associated with suicidal ideation and behavior in this population. Unique problems encountered in interviewing prepubertal children about suicidal ideation and behavior are examined in this paper. METHOD: Observations of problems encountered in interviewing prepubertal children about suicidal ideation and behavior were gleaned in the context of interviews of children admitted to a child psychiatry inpatient unit and interviews of the parents of these children. RESULTS: Unique problems include difficulties in assessment of suicidal intent, impact of cognitive development, particularly of the concept of death, interaction between current emotional state and memory of previous suicidal episodes, characteristics of play associated with suicidal states, effects of parents' attitudes toward assessment on information gathering, and the impact of certain risk factors on cognition and behavior during the interview. CONCLUSION: Interviewing children about suicidal ideation and behavior necessitates that the clinician attend to multiple elements of the interview simultaneously. These interviews are further complicated by the stressful thoughts and feelings that can be raised in both clinician and child in reaction to exploring the child's suicidal ideation and behavior. Additional research is needed to refine the process of reliable interviewing of children about suicidal ideation and behavior and to develop instruments both to quantitate the different elements of these interviews and to guide the clinicians conducting them. PMID- 8005897 TI - The confusion between bipolar disorder and schizophrenia in youth: where does it stand in the 1990s? AB - OBJECTIVE: To determine whether the bias against diagnosing bipolar disorder in youth continues, and if so, why. METHOD: Subjects are bipolar and schizophrenic patients taken from a county-wide sample of first admissions for psychosis. Patients are given structured interviews and consensus diagnoses at intake and 6 months. Age of onset of psychosis, gender, and 6-month consensus diagnosis between both groups are compared. To assess diagnostic bias, diagnostic stability and facility discharge diagnoses are examined in young (aged 15 through 20 years) versus adult (aged 30 through 40 years) patients. RESULTS: Bipolar disorder and schizophrenia are diagnosed at similar rates in younger age groups by 6-month consensus. However, bipolar disorder was underdiagnosed by Suffolk County's psychiatric hospitals in the youth. The stability of both disorders in both age groups was similar and excellent. Schizophrenia had a slightly older age at first psychosis than bipolar disorder and an equal gender representation. Bipolar disorder in males was rare after age 30. CONCLUSION: Community psychiatrists no longer call young bipolar patients schizophrenic, but they underdiagnose bipolar disorder. The more complicated nature of early-onset bipolar disorder may be a contributing factor. PMID- 8005898 TI - Rate and predictors of prepubertal bipolarity during follow-up of 6- to 12-year old depressed children. AB - OBJECTIVE: To investigate the rate and predictors of onset of DSM-III bipolar I and bipolar II disorders among 6- to 12-year-old prepubertal subjects with DSM III major depressive disorder (MDD) who were followed for a 2- to 5-year period. METHODS: This was a prospective, blindly rated study of 79 children with MDD and 31 normal control children matched for age, gender, and socioeconomic status. Subjects and a second informant were assessed at 4-month intervals using the Kiddie Schedule for Affective Disorders and Schizophrenia-Present Episode Version 1986 modified to include 4-month interval ratings and to include DSM-III diagnoses. Family history (FH) was assessed using the FH-Research Diagnostic Criteria obtained from the mother about the subject's first- and second-degree relatives. RESULTS: Bipolarity developed in 31.7% (N = 25) of the children with MDD at a mean age of 11.2 +/- 2.0 years and 80% were prepubertal. Loaded FH and multigenerational FH were significantly associated with bipolar I. Neither prior nor current use of tricyclic antidepressants nor atypical depressive features were predictive. CONCLUSIONS: These findings strongly support the need to educate families of children with prepubertal-onset MDD about the possibility of the emergence of manic and hypomanic symptoms to encourage early recognition and appropriate treatment. PMID- 8005899 TI - Basal thyroid indices in adolescent depression and bipolar disorder. AB - OBJECTIVE: Abnormalities of the thyroid axis are documented in adult mood disorders. The most consistent findings have been observed in major depressive disorder with elevations of thyroxine (T4) or free-T4 (fT4) within the euthyroid range that decrease with treatment. The literature on adolescents is limited, and it is unknown whether similar findings might be present in this population. METHOD: First admissions to a university hospital adolescent psychiatry unit were reviewed. Fourteen depressed and 13 manic patients satisfied inclusion and exclusion criteria. None had a history of thyroid illness or medical illness or were taking medications known to affect thyroid function. Basal serum thyrotropin, T4, fT4, triiodothyronine (T3), reverse-T3, free thyroxine index (FTI), and T3 resin uptake levels were compared with those of a group of adolescent normal controls. RESULTS: T4 (but not fT4) was elevated in depressed and manic patients compared with controls (p < .05). In manic patients, T3 was decreased and reverse-T3 was increased (p < .05). There were no significant differences in relation to age, sex, or suicidality. CONCLUSIONS: We observed significant differences in basal thyroid hormone levels in depressed and manic adolescents. Our results suggest the presence of abnormalities of thyroid function in adolescent mood disorders similar to those described in mood disordered adults. PMID- 8005900 TI - Psychiatric comorbidity in hospitalized adolescent substance abusers. AB - OBJECTIVE: Co-occurrence of psychiatric disorders was investigated among 52 adolescent substance abusers and 23 non-substance-abusing adolescents with conduct and/or oppositional defiant disorders, admitted to the same inpatient facility. METHOD: During independent face-to-face interviews with parent(s) or caretaker(s) and subjects, the Schedule for Affective Disorders and Schizophrenia for School-Age Children-Epidemiologic Version was administered to collect data on substance abuse, psychopathology, and sociodemographic characteristics, such as age, gender, home situation, and psychosocial stressors. A semistructured interview was used to identify the presence of substance abuse and other psychopathology among first-degree family members. Substance abuse was diagnosed according to both DSM-III-R and Halikas criteria. RESULTS: Excluding conduct and oppositional defiant disorders, 85% of the substance abusers versus 65% of the non-substance abusers demonstrated psychiatric comorbidity. Substance abusers had a higher incidence of dysthymia, major depression, social phobia, and "other" diagnoses than did the comparison group (p < .05), in which oppositional defiant disorder, conduct disorder, and attention-deficit hyperactivity disorder prevailed. Overanxious disorder was predominant among female (p = .022) and conduct disorder among male substance abusers (p < or = .002). Psychopathology preceded or coincided with substance abuse, except for major depression. No correlation between the severity and type of substance abuse and the number and degree of various coexisting psychopathologies was found. Psychopathology in parents and siblings of substance abusers was similar to that of non-substance abusers. CONCLUSIONS: These data indicate that adolescent substance abusers are at high risk for comorbid psychopathology and need to be carefully evaluated for psychiatric comorbidity to provide them with a comprehensive treatment plan. PMID- 8005901 TI - Disulfiram for alcohol use disorders in adolescents. AB - Alcohol abuse and dependence in adolescents is a serious health concern with significant morbidity and mortality. Disulfiram has been used to treat alcoholism in adults since 1948, but there are no known reports of disulfiram treatment in minors. Case reports are presented on the use of disulfiram in two adolescent males with alcohol dependence and strong family histories of alcoholism. Prolonged abstinence from alcohol occurred in the first case, whereas poor pharmacological compliance resulted in an early relapse in the second case. The judicious use of disulfiram in adolescents is recommended for consideration in those with alcohol use disorders. A protocol is proposed that recommends a thorough medical and psychiatric evaluation, documentation of a serious alcohol use disorder, careful assessment for comorbid diagnoses, family involvement when possible, and obtainment of informed consent that encompasses education about the nature and effects of disulfiram along with its potential interactions with other medications. PMID- 8005902 TI - Psychosocial stressors more common in adolescent suicides with alcohol abuse compared with depressive adolescent suicides. AB - OBJECTIVE: Relationships between stressors and psychiatric diagnoses were studied among 13- to 19-year-old adolescent suicide victims with alcohol abuse/dependence (N = 14), depressive disorders (N = 18), and the remainder (N = 21). METHOD: The study included all adolescent suicides (N = 53) during a nationwide psychological autopsy study of suicides in Finland during a 12-month period (N = 1397). The data were collected through interviews with the victims' parents and health care personnel and from official records. RESULTS: Interpersonal separations and difficulties regarding discipline or the law were common recent stressors among the alcohol abuse victims, and interpersonal conflicts and somatic illness among those with depressive disorders. Compared with the depressive victims, an unstable earlier family history was more common among the alcohol abusers. The accumulation of stressors and weakened parental support during the previous year were also more frequently found in the alcohol abuse victims. CONCLUSIONS: The results indicate that specific psychosocial stressors may be critical for suicidal adolescents with different diagnoses. In the evaluation of suicidal adolescent substance abusers, particularly recent interpersonal separations and family support need to be carefully weighed. Disruptions in the adolescent's interpersonal relationships, excess accumulation of stress, and lacking support from the family may be warning signs of suicide potential and indications for additional social support, for more intensive treatment, or for a change in the treatment setting. PMID- 8005903 TI - Perceived family functioning and adolescent suicidal behavior. AB - OBJECTIVE: Family problems increase the risk of adolescent suicidal behavior, but the specific dimensions of family functioning related to adolescent suicidal ideation and suicide attempts have not been identified clearly. This study examined the relationship between family functioning and adolescent suicidal ideation and suicide attempts. Participating adolescents included psychiatric inpatients who had attempted suicide (n = 35), high school students reporting suicidal ideation (n = 33), nonsuicidal psychiatric inpatients (n = 29), and nonsuicidal high school students (n = 37). METHOD: The Family Assessment Measure was used to assess adolescents' perceptions of family functioning on two levels: (1) the family system and (2) parent-adolescent dyadic relationships. RESULTS: The suicidal psychiatric inpatients and the suicidal high school students did not differ in their perceptions of family functioning and mother-adolescent relationships. However, both suicide groups reported more distress and family dysfunction than did the nonsuicidal high school students. Perceived family functioning and mother-adolescent relationships were significantly correlated with levels of depression, hopelessness, and self-esteem. CONCLUSIONS: Family functioning is important to consider when assessing and treating adolescents for suicidal behavior. PMID- 8005904 TI - Brief cognitive-behavioral treatment for adolescent suicide attempters and their families. AB - OBJECTIVE: This article describes a brief, standardized, cognitive-behavioral treatment program for adolescent suicide attempters and their families. METHOD: Successful Negotiation Acting Positively (SNAP) treatment consists of a series of structured activities that create a positive family atmosphere, teach problem solving skills, shift the family's understanding of their problems to troublesome situations rather than difficult individuals, and build confidence in the treatment professional, thereby reducing conditions associated with future attempts. RESULTS: SNAP treatment has been systematically administered to more than 100 suicidal adolescents and their families as part of an ongoing treatment study. Although these results are not yet available, our initial experience suggests that SNAP treatment can be delivered in a reliable fashion and is well accepted by both patients and therapists. CONCLUSIONS: Although suicidality in youth constitutes a major public health problem, few therapeutic interventions have been developed specifically for suicidal adolescents. SNAP treatment addresses a number of issues critical to successful interventions with this population, including their historically poor treatment compliance, the need for family involvement in treatment, and an emphasis on coping and problem-solving strategies. Moreover, the brief, structured format of SNAP treatment is consistent with the growing trend toward standardized, empirically tested, and cost-efficient interventions. PMID- 8005905 TI - A clinical follow-up of delinquent males: ignored vulnerabilities, unmet needs, and the perpetuation of violence. AB - OBJECTIVE: This paper describes the adult adaptation of a group of 97 formerly incarcerated male delinquents. METHOD: Follow-up clinical interviews were administered to subjects, approximately 9 years after discharge from juvenile corrections. The records of the correctional school, state police, FBI, state psychiatric hospitals, and state health department also were reviewed. RESULTS: All but six had adult criminal records, most for violent crimes. Only 10% were graduated from high school; 30% received minimal job training; most worked sporadically at unskilled jobs. Few married. Although 35 had fathered children, only 5 were living with them. Psychiatric treatment for identified vulnerabilities was negligible. Upon discharge, the most neuropsychiatrically impaired and violent subjects tended to be placed in adult corrections; the most intact were placed in special schools and psychiatric hospitals. Numbers of vulnerabilities continued to contribute most significantly to violent outcome regardless of placement. Placement in families was associated with fewer adult aggressive offenses than was institutional placement, even while controlling for vulnerabilities and early juvenile violence. CONCLUSION: Based on their well documented early vulnerabilities and needs, this sample of delinquents did not obtain the kinds of supports subsequent to juvenile incarceration that might have enabled them to function independently in society. PMID- 8005906 TI - DSM-IV field trials for the disruptive behavior disorders: symptom utility estimates. AB - OBJECTIVE: We tested the predictive utility of symptoms for proposed DSM-IV definitions of the disruptive behavior disorders using indices corrected for symptom and diagnosis base rates. METHOD: The field trials sample consisted of 440 clinic-referred youths who were consecutive referrals to a heterogeneous group of mental health clinics. Multiple informants were interviewed to determine the presence of symptoms and diagnoses. RESULTS: Some symptoms which were either not in DSM-III or DSM-III-R, or were modifications of DSM-III-R symptoms, had greater diagnostic efficiency than did several existing symptoms. Symptom utility estimates were generally similar for different ages and genders, although some interesting age and sex trends emerged for a few symptoms. CONCLUSIONS: The results supported the inclusion of more restricted definitions of "lying" and "truancy" to increase their association with a conduct disorder diagnosis and they supported the elimination of "swearing" in the oppositional defiant disorder criteria. In addition to their relevance for developing optimal criteria for DSM IV, these results can aid DSM-IV users by providing a useful guide to the relative efficiency of individual symptoms based on data from a large heterogeneous clinic population. PMID- 8005907 TI - Family structure and aggressive behavior in a population of urban elementary school children. AB - OBJECTIVE: This report examined associations between family structure and 393 fourth-grade children's aggressive behavior. METHOD: In an epidemiologically defined urban community population, both teacher and parent ratings of child aggressive behavior were examined among family structures that reflected current demographics. Relative risks for teacher- and parent-rated child aggressive behavior in mother-alone households were compared with those in the next most prevalent family structures (mother-father, mother-grandmother, and mother-male partner families). RESULTS: With all income groups combined, teachers rated boys and girls in mother-alone families as more aggressive relative to mother-father families. Among low-income families, the protective effects for mother-father families were not apparent, and mother-male partner families were associated with an increased risk for teacher-rated aggression for boys. CONCLUSION: Absence of and type of second adult present, child gender, home and school context, and income were important factors that moderated the associations between family structure and child aggressive behavior in this urban setting. PMID- 8005908 TI - Treatment outcome among children with externalizing disorder who terminate prematurely versus those who complete psychotherapy. AB - OBJECTIVE: To compare the clinical dysfunction at the end of treatment of children who dropped out of therapy prematurely (dropouts) versus those who completed treatment (completers). We predicted that (1) children who terminated prematurely would show greater impairment at the end of treatment than would children who completed treatment, and (2) the differences at posttreatment would result from subject selection variables and severity of child dysfunction at pretreatment rather than from termination of treatment, per se. METHOD: Children (N = 75, aged 4 to 13 years) referred for oppositional, aggressive, and antisocial behavior formed three groups: dropouts, completers, and completers matched to dropouts on subject and demographic variables and severity of child dysfunction. RESULTS: At the end of treatment children who terminated prematurely showed greater impairment at home, at school, and in the community, compared with children who completed treatment. Outcome differences were less evident between dropouts and completers when pretreatment child severity of dysfunction was controlled. CONCLUSIONS: The findings suggest that selection factors and severity of impairment may relate both to attrition and limited responsiveness among patients who continue. PMID- 8005909 TI - Modifying quiet room design enhances calming of children and adolescents. AB - OBJECTIVE: To determine whether altering design of a quiet room (QR) produced more rapid calming of agitated or aggressive hospitalized children. METHOD: One of five similar QRs was modified by painting the white walls tea rose, carpeting the vinyl floor, and painting a picturesque mural on one wall. The effects of these modifications were assessed in 19 patients (mean age = 9.6 years), using a within-subjects, repeated-measures design. Overt Aggression ratings were made at the time of placement, and at 5-minute intervals thereafter, until the child was dismissed. Children were blind to the fact that a study was being conducted; raters and staff were not. RESULTS: Total aggression ratings were 45% lower in the modified QR than in the standard QR (p < .03), and initial aggression scores fell by 50% during 5 minutes of placement in the modified QR, but only after 20 minutes of placement in the standard QR (p < .0001). Motor excitement and verbal aggression were the two component factors most strongly influenced by QR design. CONCLUSION: This preliminary report suggests that it may be possible to modify QRs to facilitate calming of aggressive, agitated children and provides preliminary support for redesign of QRs. PMID- 8005910 TI - Maltreatment in psychiatrically hospitalized children and adolescents with developmental disabilities: prevalence and correlates. AB - OBJECTIVE: The goals of this study were (1) to determine the prevalence of child maltreatment in hospitalized children and adolescents with developmental disabilities and concomitant psychiatric disorders, and (2) to identify the contribution of specific mother and child characteristics to the use of more severe disciplinary practices by mothers. METHOD: One hundred thirty-eight psychiatrically hospitalized children and adolescents with developmental disabilities and mothers were assessed using a semistructured interview (Child Abuse and Neglect Interview Schedule) examining factors associated with risk of child maltreatment, and questionnaires measuring maternal and child functioning. The Child Abuse and Neglect Interview Schedule and hospital charts were then used to derive ratings on the prevalence and severity of child maltreatment. RESULTS: Findings revealed that 61% of children had experienced some form of severe maltreatment by a care provider in their lifetime. Regression analysis indicated that interactions between high levels of social functioning and disruptive/oppositional behaviors and younger age in children, and low levels of social support and increased anger reactivity in mothers, were most predictive of mothers' use of severe disciplinary practices. CONCLUSIONS: Maltreatment in psychiatrically hospitalized children and adolescents with disabilities is very prevalent, and it warrants careful clinical assessment. In the psychiatric setting, families in which the child is younger, higher functioning, and behaviorally disruptive, and where mothers have little social support and exhibit increased anger reactivity, are at especially elevated risk. PMID- 8005911 TI - Comprehensive management of trichotillomania in a young autistic girl. AB - The coexistence of trichotillomania and autistic disorder has rarely been reported in psychiatric literature. The current study describes successful treatment of trichotillomania in a young autistic girl, using combined clomipramine and behavioral therapy. Neither behavioral therapy, clomipramine, methylphenidate, buspirone, nor naltrexone was effective in monotherapeutic trials. We postulate a synergistic effect of combined treatment with clomipramine and behavioral therapy, suggesting that both pharmacological and behavioral treatment of hair pulling may be necessary for many patients. This model is consistent with the extant literature and suggests that future clinical trials of clomipramine for trichotillomania, in both developmentally disabled and normal subjects, must evaluate this multimodal approach. PMID- 8005912 TI - Resolved: several weeks of depressive symptoms after exposure to a friend's suicide is "major depressive disorder". PMID- 8005913 TI - The safety of desipramine. PMID- 8005915 TI - Cocaine craving. PMID- 8005914 TI - Cardiac effects and fluoxetine. PMID- 8005916 TI - MPH and thrombocytosis. PMID- 8005917 TI - Selective mutism continued. PMID- 8005918 TI - Anorexia nervosa in rural Austria. PMID- 8005919 TI - Newer hypoglycaemic agents-its relevance. PMID- 8005920 TI - Hyperprolactinemia and hypogonadism. PMID- 8005921 TI - Modification in sucrose tolerance test with acarbose, guargum and their combination in patients with non-insulin dependent diabetes. AB - The study was undertaken to assess the efficacy guargum, Acarbose and their combination in modifying the sucrose absorption in patients of non Insulin dependent diabetes mellitus (NIDDM). Fifty patients of NIDDM were randomly distributed in three groups. Group A had 20 patients who received 20 grams of guargum, Group B had 10 patients who received 100 mg of Acrabose, Group C had 20 patients who received 10 grams of guargum and 50 grams of Acrabose. All the patients underwent 50 grams sucrose tolerance test with and without the trial drugs. Blood glucose levels were determined at 0, 30, 60, 90 and 120 minutes after sucrose loading. With the drugs, there was a significant decrease in the blood glucose levels at all time intervals (p < 001) in all the three groups. In all the three groups the blood glucose levels with the trial drugs was significantly lower (p < 001) than without the drug. It was seen that acarbose alone and guargum alone did not differ significantly in reducing the blood sugar level whereas combination of two produced significantly greater reduction in blood glucose levels than either of the drug used alone. Thus both guargum and acarbose are equally effective in modifying the absorption of sucrose. When combined in half the dosage they have synergistic effect and the reduction in blood glucose level is greater than either of the drug used alone. PMID- 8005923 TI - Prognosis of single unprovoked seizure. AB - 201 patients (131 males and 70 females) with mean age of 18 years (range 5-55 years) who presented at median of 6 days after the onset of first unprovoked seizure were studied. They were followed for a mean period of 60 months (range 12 84 months). One hundred and fifty four (76%) patients were treated with anticonvulsant medication (group A) on a non-randomized basis and the remaining 47 patients (24%) were not treated (group B). Both the groups were comparable for age, sex, type of seizure and interval between onset of seizure and consultation. The cumulative risk of recurrence for entire study group was 24% at 1 month, 32% at 6 months, 34% at 12 months, 35% at 24 months and 36% at 36 months. The cumulative risk of recurrence in group A was 23%, 30%, 32%, 33% and 33% as compared to 28%, 36%, 40%, 43% and 45% at 1, 6, 12, 24 and 36 months respectively (p > 0.05). Maximum number of recurrences (67%) occurred within 1 month. No recurrence occurred after 36 months after the onset of first seizure. Age at onset, sex, seizure type, family history of seizure, EEG abnormalities and nature of antiepileptic drugs did not influence the risk of recurrence. PMID- 8005922 TI - Hyperprolactinemia in women--a series of 71 cases. AB - Seventy one cases of hyperproloactinemia (HPRL) in women were seen over five years. Of these, twenty five had pituitary tumors, thirty three had functional HPRL, five had drug induced HPRL and four had hypothyroidism. Surgery was undertaken in fifteen women, rest were treated with bromocriptine. There were thirteen pregnancies in patients with tumor after treatment. Seven of thirty three patients with functional HPRL conceived. No patient had tumor expansion or recurrence during pregnancy. Bromocriptine was required for most patients. PMID- 8005924 TI - An eight year review of diseases in rural Rajasthan. AB - To study the pattern of various medical diseases seen during specialist medical rural practice, we undertook an analysis of 1362 consecutive cases seen over an eight year period at a rural centre in Rajasthan. Analysis showed that infective diseases e.g. tuberculosis, acute infections, and infection related diseases of the gastrointestinal tract, skin, nervous system and heart formed the largest group with 724 patients (53.2%) as compared with chronic non-infective systemic diseases which were seen in 638 patients (46.8%). Cardiac diseases were seen in 306 patients (22.5%) which included 110 cases with ischaemic heart disease, 38 with hypertension, 110 with rheumatic heart disease, and 48 with other conditions. It is concluded that in rural practice acute and chronic infective diseases, and infection related illnesses (e.g. rheumatic heart disease) are more common than degenerative non-communicable diseases. Thus, more attention is needed in the field of infective diseases which are amenable to prevention and cure. Cardiovascular diseases form a sizeable majority of non-infective medical illnesses. PMID- 8005925 TI - Apolipoproteins A-1 and B as predictors of angiographically assessed coronary artery disease. AB - Serum lipids, lipoproteins, apolipoproteins (A-1 and B) were determined in 225 patients with angiographic evidence of coronary artery disease (having abnormal coronary angiogram and positive exercise stress test), and 112 patients without any clinical and/or angiographic evidence of coronary artery disease. The variable with the strongest association with coronary artery disease was the ratio of apo B/A-1. Thus, the determination of apolipoproteins yielded complementary information in this case control study and warrants further study in a prospective setting. PMID- 8005926 TI - Awareness of cholesterol as coronary risk factor among general practitioners at Jaipur. AB - Widespread information about preventive measures has decreased incidence of coronary artery disease (CAD) in developing countries. However this trend is not seen in India. Cholesterol and other lipoproteins play important role in CAD. In order to assess whether this information has reached General Practitioners (GP's) and their action regarding the recommendations of the US National Cholesterol Education Programme (NCEP), G.P.'s were assessed with the help of a questionnaire. The response rate to the questionnaire was 78.4% of the total G.P.'s of the city. The findings of the study were compared to the NCEP guidelines. Results indicate that, "Ideal", "High" and cholesterol levels dietary needing precautionary measures intervention (ie. 198.2 +/- 13 mg/dl, 256.1 +/- 32 mg/dl and 247.9 +/- 26 mg/dl respectively) were similar to the NCEP guidelines. Levels where therapy is recommended (ie 293.9 +/- 34 mg/dl) is significantly more than NCEP guidelines. Though 77.1% of doctors were aware of protective effect of HDL cholesterol (ie 51.1 +/- 6 mg/dl), routine measurement of lipid profile was undertaken by only 57.1% doctors with mean age of recommendation being 34.1 +/- 11.6. Routine dietary advice and cholesterol estimation was done in 71.4% patients with CAD and 67.3% of patients with hypertension and diabetes. Analysis of action taken falls short of the NCEP recommendations and indicates a need for intensive training of the G.P.s. PMID- 8005927 TI - Primary lymphoreticular tumors of the orbit. AB - Primary orbital lymphomas are rare. We report nine such cases (4 with DWDL, 3 with DPDL, 1 with DHL and 1 unclassifiable lymphoma). All patients achieved clinical complete remission (CR). Of those who completed treatment more than a year ago, three continue to be in CR at 17, 24 & 25 months and two are lost to follow up. PMID- 8005928 TI - Liver cysts in patients with autosomal dominant polysystic kidney disease. PMID- 8005929 TI - Interobserver comparison of cardiac chamber size assessment by M-mode echocardiography. PMID- 8005930 TI - Intravenous metoprolol in hypertensive urgencies and emergencies. PMID- 8005932 TI - Congenital factor XIII deficiency. PMID- 8005931 TI - Current trends in the treatment of hypertension. PMID- 8005933 TI - Tracheal schwannoma. PMID- 8005934 TI - Macroprolactinoma expansion during pregnancy. PMID- 8005935 TI - Fulminant right sided endocarditis in a malnourished patient. PMID- 8005936 TI - Hyperparasitaemia due to Plasmodium falciparum malaria. PMID- 8005938 TI - Eosinophilic gastro enteritis. PMID- 8005937 TI - Left ventricular pseudoaneurysm. PMID- 8005939 TI - Antiepileptic drug induced osteomalacic myopathy with hyperparathyroidism and nephrolithiasis. PMID- 8005940 TI - Hypoparathyroidism with benign intracranial hypertension. PMID- 8005941 TI - Renal involvement in Fabry's disease. PMID- 8005942 TI - Autosomal dominantly inherited retinitis pigmentosa with a severe clinical course. PMID- 8005943 TI - Partial central diabetes insipidus following tuberculous meningitis. PMID- 8005944 TI - Spontaneous stuttering priapism in sickle-cell disease. PMID- 8005945 TI - Hypertension in alcoholic population of Jhabua. PMID- 8005946 TI - Neuroleptic malignant syndrome. PMID- 8005947 TI - Primary hypokalaemic periodic paralysis--a further experience. PMID- 8005948 TI - Hypothyroidism presenting with polycystic ovary syndrome. PMID- 8005949 TI - Cystic fibrosis in one family. PMID- 8005950 TI - Management of hypertension in diabetes. PMID- 8005951 TI - Hyperkalemic periodic paralysis associated with thyrotoxicosis. PMID- 8005952 TI - Is a hypertensive always a hypertensive? PMID- 8005953 TI - Is a hypertensive always a hypertensive? PMID- 8005954 TI - Conducting examinations in medical colleges; how to raise standards! PMID- 8005955 TI - Association of diabetes mellitus and smoking. PMID- 8005957 TI - An easy method of spirometry. PMID- 8005956 TI - Mental stress and myocardial ischaemia. PMID- 8005958 TI - Misoprostol (Cytotec) in NSAID gastropathy. PMID- 8005959 TI - Live oral TY 21a--typhoid vaccine. PMID- 8005960 TI - Toxicity of oral iron chelator L1. PMID- 8005961 TI - Streptokinase in acute myocardial infarction. PMID- 8005962 TI - Continuous arteriovenous haemofiltration and haemodialysis. PMID- 8005963 TI - Endemic cretinism: the Indian scene. PMID- 8005964 TI - Assessment of intravenous streptokinase therapy in acute myocardial infarction. AB - Ten patients presenting within 6 hours of myocardial infarction, without contraindication for thrombolytic therapy, were given intravenous (IV) streptokinase (STK) 750,000 units in 15-30 min by infusion followed by anticoagulant therapy. Treatment was started within 241-360 min after the onset of symptoms. Fifteen other patients were given standard treatment without STK. Reperfusion was observed after a mean duration of 46 min in 7 patients in the STK group and none in the non-STK group. The results of IV STK thrombolytic therapy are comparable with those of previous studies using IV STK. PMID- 8005965 TI - Continuous renal replacement therapy in critically ill patients with renal failure. AB - Continuous arterio-venous and veno-venous haemodiafiltration (CAVHD, CVVHD), combine convection and diffusing solute clearance. We performed CVVHD on critically ill patients with renal failure, of whom 15 were on inotropic support and 10 on ventilators. Satisfactory diafiltration could be performed in all the patients with adequate solute and fluid removal. The main complication was clotting of the filter. The procedure was simple, safe and could be done by staff with no special training in dialysis technology. PMID- 8005966 TI - Clinical study of endemic cretinism in south Sikkim. AB - One hundred individuals suffering from Endemic Cretinism were studied. There were 55 males and 45 females. 62% of the cretins had visible goitre. Thirty nine (62.9%) goitrous cretins had grade II goitre. Neurological cretinism was the predominant type encountered (99%) and Myxoedematous cretinism was seen in only one patient. The most salient neurological feature was deaf-mutism seen in 74%. Findings in the motor system were, apart from deaf-mutism, the most characteristic feature of the condition on clinical examination. 58% had exaggerated deep tendon reflexes and 31% had extensor plantar response. Squint was noticed in 29%. Familial aggregation was noticed and was striking. Endemic cretinism is a distinctive and easily identifiable clinical entity and is an important indicator of the severity of iodine deficiency in a community. PMID- 8005967 TI - Autoantibodies in thalassaemia major: relationship with oral iron chelator L1. AB - Ninety patients with thalassaemia major were investigated for the occurrence of antinuclear antibodies (ANA), and those with ANA were tested for antibodies to histones (AHA). ANA were detected in 7 of 27 thalassemics on oral iron chelator L1, and in 2 of 63 thalassaemics not on L1 (p < 0.01). AHA were seen in 4 of 7 thalassemics receiving L1 with positive ANA, and in none of the 2 not receiving L1 (p < 0.03). Joint pains were seen in patients receiving L1, but in none of the patients not receiving L1. There was no correlation between hepatitis B or HIV positivity and presence of ANA or joint pains. While some amount of background ANA-positivity was found in patients with thalassaemia major, it was significantly more in patients receiving L1. Laboratory evidence of drug-induced lupus-like reaction was seen only in patients who received L1. In view of serious concerns about the safety of L1 and wide variations in the incidence and severity of adverse reactions reported by different sources, an urgent regulatory audit of all trial centres is essential. PMID- 8005968 TI - Immunosurveillance of transfusion dependent thalassaemia and hepatitis B vaccination. AB - The study evaluates the probable alteration of the immune system in multitransfused thalassaemics and the modification of their immune response following administration of hepatitis B virus (HBV) vaccine. B-thalassaemics (n = 50) and EB-thalassaemics (n = 30) who received multiple blood transfusion for the chronic anaemic status had significant iron overload. They had high prevalence for hepatitis B carrier state and almost all were exposed to hepatitis B virus during the course of transfusion as shown by the positivity of hepatitis B virus markers. Thalassaemics in presence of iron overload have altered immune status in terms of depressed T-lymphocytes and raised immunoglobulins G and M. However, they showed 100 per cent seroconversion with production of antibody to hepatitis B surface antigen following Hepatitis B vaccination. PMID- 8005969 TI - C-peptide profiles in young diabetics. AB - Fifty-six patients who had been diagnosed diabetic prior to the age of 30 were evaluated to determine the C-peptide (CP) secretory response to a glucose load. These individuals were classified clinically as having insulin dependent (IDDM = 18); non-insulin dependent (NIDDM = 19) and insulin requiring diabetes (IRDM = 19). Insulin dependent diabetics had lower basal CP levels (0.44 +/- (SE) 0.1 ng/ml) which were not stimulated by hyperglycaemia (0.55 +/- 0.13 ng/ml) as compared to controls (basal CP = 1.6 +/- 0.2 and peak 6.2 +/- 0.8 ng/ml). Non insulin dependent diabetics and insulin requiring diabetics could be divided broadly into two groups - one, a set of patients with low basal CP levels (NIDDM = 0.63 +/- 0.09 ng/ml) (IRDM = 0.38 +/- 0.08 ng/ml) and a blunted response to a glucose load (peak response NIDDM = 0.83 +/- 0.05 ng/ml, IRDM = 0.59 +/- 0.12 ng/ml) and a second group who had CP reserve evident in both fasting (NIDDM = 1.6 +/- 0.2 ng/ml; IRDM = 2.1 +/- 0.6) and post-glucose levels (Peak Response NIDDM = 4.6 +/- 0.4 ng/ml; IRDM = 3.0 +/- 0.6 ng/ml). Growth Hormone (GH) and cortisol levels were found to be high in patients with IDDM and IRDM with no insulin reserve and these did not suppress during the oral Glucose Tolerance Test. NIDDM patients with no insulin reserve had normal GH and high cortisol levels. It is emphasized from this study that insulin sensitivity is as important as the insulin secretory status in determining the presenting features of diabetes mellitus in the young. PMID- 8005970 TI - Prognosis and management of membraneous nephropathy. AB - Patients of idiopathic membranous nephropathy (MGN) were randomly assigned to received steroid and cyclophosphamide every other month (Gr-I) and steroid alone (Gr-II). Of 36 patients in Gr.I, 33 patients achieved complete remissions, 2 had relapsing course with remission on further courses of therapy and only one has reached end stage renal failure. In contrast, of the 35 patients in Gr. II, 15 (P < 0.001) achieved complete remission, 7 are in partial remission, 5 have no response, another 5 have deterioration of renal function of which two required dialysis, and 3 have relapsing course after the initial remission. Mean follow up period was 46 +/- 10.2 months. We conclude that steroid and cyclophosphamide every other month is highly effective in achieving remission in patients with membranous nephropathy. PMID- 8005971 TI - Serological characterisation of Neisseria gonorrhoeae by co-agglutination technique. AB - Antibiotic susceptibility pattern in cases of acute gonococcal urethritis, was studied by single disc diffusion technique and minimum inhibitory concentration (MIC) by agar dilution technique were determined for 5 antibiotics, viz penicillin, ampicillin, tetracycline, gentamicin and norfloxacin. All the penicillinase producing Neisseria gonorrhoeae (PPNG) and non-PPNG strains were sensitive to norfloxacin. 72% of the isolates belonged to serogroup WII/WIII by co-agglutination technique. PMID- 8005972 TI - Polymyositis--a review and follow up study of 24 cases. AB - Twenty-four cases of polymyositis, 3 (12.5%) of them Dermatomyositis, have been treated and followed up for over 12 years. Majority (75%) were males. Inflammatory lesion was the cause in 18 (75%), collagen disease in 4 (16.7%) and malignancy in 2 (8.35%). Presenting features were fever (100%), proximal muscle weakness (95.8%) and tenderness (54.2%), facial and respiratory muscle weakness (4.2%). Raised CPK and transaminases, electromyogram abnormality and positive muscle biopsy were recorded in all. All were treated with steroids. Complication/associations noted were arthalgia (25%), dysphagia (20.6%), peripheral neuritis (8.35%), diabetes mellitus (4.2%), pulmonary fibrosis (4.2%) and malabsorption (4.2%). Fourteen cases (58%), all of inflammatory aetiology, recovered completely. Seven cases (29.2%) developed permanent atrophy of affected muscles. Cases with collagen disease and malignancy fared worse and deteriorated because of the primary disease. PMID- 8005973 TI - Evaluation of Manning's criteria in the diagnosis of irritable bowel syndrome. AB - Six symptoms of Manning et al are widely used in clinical practice to diagnose irritable bowel syndrome (IBS). We studied 123 patients to evaluate the diagnostic value of Manning's criteria, using a preformed bowel symptom questionnaire which included these six symptoms. This study included 65 patients with IBS, 35 patients with non-ulcer dyspepsia, 23 patients with organic diseases of colon and 45 healthy controls. Sensitivity of presence of three or more symptoms of Manning's criteria discriminating irritable bowel syndrome from all other groups was 66.1%. Manning's criteria discriminated irritable bowel syndrome from organic diseases of colon with specificity and positive predictive value of 66.9% and 82.6%. When irritable bowel syndrome was compared with non-ulcer dyspepsia and healthy controls, specificities of Manning's criteria were 91.4% and 93.3% and positive predictive values 93.4% and 93.4% respectively. PMID- 8005974 TI - Gliclazide in the treatment of obese non-insulin dependent diabetic patients. AB - The clinical efficacy of gliclazide and its effect on plasma glucose, body weight and serum lipids was assessed in a 3 months open trial of 30 obese, Non-Insulin Dependent diabetes mellitus (NIDDM) patients who failed to respond to diet therapy alone. By day 20, the mean post prandial plasma glucose (PPG), and fasting plasma glucose (FPG) were significantly reduced from 276 +/- 13.5 to 195.8 +/- 13.9 mg % (p < 0.01) and 179 +/- 9.3 to 130.6 +/- 9.6 mg % (p < 0.01) respectively. This early glycaemic control was maintained, and by 3 months a further significant decrease occurred in PPG to 156.46 +/- 7.6 mg % (p < 0.01), and FPG to 106.9 +/- 3.8 mg % (p < 0.01). Mean glycosylated haemoglobin (HbA1c) was reduced from 10.3% to 7.7%. The drug had a favourable effect on serum lipids, significantly increasing high density lipoprotein fraction of cholesterol (HDL-C) (p < 0.034), and decreasing low density lipoprotein fraction of cholesterol (LDL C) (p < 0.049). Mean body weight showed a significant reduction of 1.5 kg (p < 0.003). We conclude that gliclazide is an effective hypoglycaemic agent that ensures a rapid and sustained blood glucose control with a favourable effect on lipids and body weight in obese NIDDM patients. PMID- 8005975 TI - Serum immunoglobulin E against PPD antigen in patients with pulmonary tuberculosis. AB - There is scant literature on the existence of IgE (type I allergic reactions) directed against Myocobacterium tuberculosis. To study this problem, total serum IgE (SIgE) and IgE specifically directed against the purified protein derivative of Myocobacterium tuberculosis (PPD-Sp IgE) was determined in 16 patients with AFB positive pulmonary tuberculosis (PTB) and their age and sex matched controls. Mean SIgE was significantly higher in PTB than in controls. Mild heating of the serum was necessary to detect the presence of PPD-Sp IgE which was positive in 81.3% PTB. One (6.3%) gave a class I, 9 (56.3%) gave class II and 3 (18.7%) gave class III RAST reactions. PPD-Sp IgE was absent in 3(18.7%). There were no class IV reactions. Control sera were negative for PPD-Sp IgE. Though the RAST test had a sensitivity of 80.1%, a specificity of 100% and a positive predictive value of 100%, we do not advocate this test as a diagnostic test. We have used this test to demonstrate the existence of PPD-Sp IgE and thus the existence of Type I allergic reactions against the PPD antigen of Mycobacterium tuberculosis. Its value in relation to clinical symptoms and its site of local production need further studies. PMID- 8005976 TI - Anti-lymphocyte globulin therapy in acquired aplastic anaemia. AB - Thirty five patients with acquired aplastic anaemia (AAA) were treated with anti lymphocyte globulin (ALG). Fifteen (42.9%) had non-severe aplastic anaemia (NSAA), 14 (40%) severe aplastic anaemia (SAA) and 6 very severe aplastic anaemia (VSAA). There were 17 (48.6%) responders to the first course of ALG while 2 out of 5 (40%) responded to a second course, the overall response rate being 54.3%. Eleven out of 15 (73.3%) with NSAA responded, 8 out of 20 (40%) with SAA responded while none of VSAA responded. All the non-responders have died. Out of the responders, 1 died of non-A non-B hepatitis, and 1 with relapse of AA and sepsis. One has developed paroxysmal nocturnal haemoglobinuria (PNH) and one myelodysplasia. Another 2 needed infrequent red cell transfusion support. Remaining 13 (37.1%) are asymptomatic and without any external support since 18 78 months (35 +/- 21). We conclude that ALG is an effective modality of treatment for patients with AAA. PMID- 8005977 TI - Adverse drug reaction monitoring in India. PMID- 8005978 TI - Platelet function in acute leukemias. AB - Bleeding time, clot retraction, platelet factor 3 availability and platelet aggregation in response to ADP, epinephrine, collagen and ristocetin were studied in 13 cases of acute leukemia which included 5 cases of acute myeloid leukemia, 2 of chronic myeloid leukemia in blast crisis and 6 of acute lymphoblastic leukemia. More than one abnormality was seen in all the patients. Defects in bleeding time, clot retraction and platelet factor 3 availability were encountered in 43% of cases. Platelet aggregation responses to all the reagents were significantly impaired. There was, however, no consistency in the pattern of the defects. PMID- 8005979 TI - Congestive heart failure--an overview. PMID- 8005980 TI - Subacute hepatic failure. PMID- 8005981 TI - Recent trends in the diagnosis of amoebiasis. PMID- 8005982 TI - Macroglossia--the presenting feature of primary amyloidosis. AB - A case of amyloidosis with macroglossia as a presenting feature is described. The patient was diagnosed to have multiple myeloma at least 1 1/2 year after amyloidosis was diagnosed. PMID- 8005983 TI - Persistent complete heart block following acute rheumatic fever in a 12 year old girl. AB - Rheumatic fever can cause a variety of cardiac conduction disturbances. A case of rheumatic fever with rare complication of narrow QRS - complex complete heart block in a 12 year old girl is presented. The complete heart block has persisted even after 12 months of followup. PMID- 8005984 TI - A pseudo adrenal tumor in an obese infant. PMID- 8005985 TI - Multiple myeloma presenting as acute paraplegia. PMID- 8005986 TI - von Willebrand's disease with gastrointestinal telangiectasia. AB - A 30-year old woman presented with recurrent and massive bleeding from gastrointestinal tract. Her coagulation profile revealed von Willebrand's disease and her endoscopic examination showed extensive telangiectasia localized to the gastrointestinal tract. The association of Von Willebrand's Disease and telangiectasia is extremely rare and hence the report. PMID- 8005987 TI - Acute pancreatitis with disseminated intravascular coagulation. AB - Acute Pancreatitis is seen very frequently. We report a case of acute pancreatitis with a rare complication of disseminated intravascular coagulation (DIC), who recovered completely. PMID- 8005988 TI - Non-cardiac pulmonary oedema in scorpion bite. AB - A 30 year old male presented with non-cardiac pulmonary oedema after scorpion bite. Clinical features, X-ray chest and ECG findings after bite and recovery are discussed. PMID- 8005990 TI - Poncet's disease. PMID- 8005989 TI - Bronchogenic carcinoma involving the aorta, superior vena cava, mediastinum and pericardium. PMID- 8005991 TI - Associate of thyroid disorders with acromegaly; and with the development of hyperplastic/dysplastic breast disorders. PMID- 8005992 TI - A case of neurotoxicity due to INH. PMID- 8005993 TI - Atypical lymphocytes in acute falciparum malaria. PMID- 8005994 TI - Efficacy and safety of human biosynthetic insulin of saccharomyces cerevisiae origin. PMID- 8005995 TI - Cesium-137 brachytherapy for epithelioma of the skin of the nose: experience with 370 patients. AB - The author has treated 370 cases of skin cancer of the nose with Cesium-137 brachytherapy. The excellent results with a low recurrence rate of 3% and good cosmetic results are compared with those reported on the literature. The method is more elegant than any reconstructive surgery, which should be reserved for extensive cases. PMID- 8005997 TI - Primary lymphoma of the uterine cervix. AB - A case of primary non-Hodgkin lymphoma of the uterine cervix is reported. The ultrasonographic and computed tomographic findings are described as well as the MRI appearance of this peculiar cervical mass. The best tumor delineation was achieved by T2-predominant and contrast-enhanced T1-weighted images. The lesion was treated successfully with external radiotherapy. PMID- 8005996 TI - Focal fatty infiltration of the liver associated with important mass effect. AB - A case of focal fatty infiltration of the liver (FFIL) with partly multinodular appearance and significant mass effect on computed tomography (CT) is presented. Mass effect in FFIL is sometimes seen with alcoholic liver disease and makes the differential diagnosis with malignant disease often difficult. Diagnosis of FFIL was confirmed on 1.5 T MR images. PMID- 8005998 TI - Intramural esophageal cyst: the role of endoscopic ultrasonography. AB - We report a case of symptomatic congenital esophageal cyst. The diagnostic approach and the role of endoscopic ultrasonography in the preoperative diagnosis, especially when computed tomography demonstrates a high attenuation mass, are emphasized. PMID- 8005999 TI - Mucocele of the appendix. AB - We describe a case of mucocele of the appendix, observed incidentally in a 42 year-old man. The plain film, ultrasound and CT features are reviewed. Adequate diagnosis and resection are important because of the risk of rupture and development of pseudomyxoma peritonei. PMID- 8006000 TI - [Pulmonary epithelioid hemangioendothelioma with hepatic secondary location]. AB - Hepatic metastases secondary to a primary pulmonary epithelioid hemangioendothelioma are demonstrated in a patient after a follow-up of 11 years. Three years after diagnosis of metastases, the patient is in good general condition. MRI of hepatic epithelioid hemangioendothelioma is not specific and histologic confirmation is mandatory. PMID- 8006001 TI - Crohn's disease and sclerosing cholangitis: CT and PTC diagnosis, with MR findings. AB - Computed tomography (CT), percutaneous transhepatic cholangiography (PTC) and magnetic resonance imaging (MRI) findings in a case of sclerosing cholangitis associated with Crohn's disease of the colon and terminal ileum are described. CT gives additional information on dilatation of peripheral bile ducts and confirms findings of PTC, i.e. a decreased arborization of the biliary tree, a nodular appearance of the common bile duct and multifocal bile duct strictures. CT findings could be recognized on MRI which provided no additional information. PMID- 8006003 TI - Functional neuronal ionotropic glutamate receptors are expressed in the non neuronal cell line MIN6. AB - We report that a non-neuronal cell line, MIN6, derived from insulin-secreting pancreatic beta-cells, naturally expresses functional ionotropic glutamate receptors. Electrophysiological recordings show that kainate, alpha-amino-3 hydroxy-5-methyl-4-isoxazole propionate (AMPA), and N-methyl-D-aspartate (NMDA) depolarize single MIN6 cells and evoke inward ionic currents. These agents also increase the intracellular calcium concentration in MIN6 cells. Furthermore, insulin secretion from MIN6 cells is stimulated by kainate, AMPA, and NMDA. The presence of AMPA/kainate and NMDA receptor subtypes is confirmed by reverse transcriptase-polymerase chain reaction. These results demonstrate that ionotropic glutamate receptors with properties similar to those in neuronal cells are expressed in a non-neuronal cell line, MIN6. Thus, MIN6 provides a useful and valuable model system for biochemical, pharmacological, and physiological studies of ionotropic glutamate receptors. PMID- 8006002 TI - Identification of type I receptors for osteogenic protein-1 and bone morphogenetic protein-4. AB - Bone morphogenetic proteins (BMPs) are multifunctional proteins, structurally related to transforming growth factor-beta (TGF-beta) and activin. TGF-beta and activin exert their effects by forming heteromeric complexes of type I and type II serine/threonine kinase receptors. We have previously identified a series of type I serine/threonine kinase receptors, termed activin receptor-like kinase (ALK)-1 to -6. ALK-5 is a TGF-beta type I receptor, whereas ALK-2 and ALK-4 are activin type I receptors. Here we investigated the binding of proteins in the BMP family to ALKs. In transfected COS cells, the binding of osteogenic protein (OP) 1 and BMP-4 to certain ALKs was observed in the absence of type II receptors, and their binding was increased after co-transfection of a BMP type II receptor from Caenorhabditis elegans, DAF-4. OP-1 bound to ALK-2 and ALK-6 efficiently, and to ALK-3 less efficiently, whereas BMP-4 bound to ALK-3 and ALK-6 efficiently. Similarly, OP-1 bound to ALK-2, ALK-3, and/or ALK-6 in various nontransfected cell lines, although the binding profiles were different between different cell types. BMP-4 bound to ALK-3 in MC3T3-E1 osteoblasts and human foreskin fibroblasts. These results suggest that ALK-3 and ALK-6 are type I receptors for OP-1 and BMP-4; in addition, ALK-2 is a type I receptor shared by activin and OP 1, but not by BMP-4. PMID- 8006004 TI - A mutant of protein phosphatase-1 that exhibits altered toxin sensitivity. AB - A chimeric mutant was constructed in which a 4-amino acid region (GEFD, residues 274-277) of rabbit muscle protein phosphatase-1 was replaced with the sequence YRCG corresponding to residues 267-270 of rabbit protein phosphatase-2A. This was based on the findings of a gene mutation in okadaic acid-resistant cells which results in a Cys-->Gly conversion in protein phosphatase-2A. The YRCG mutant of protein phosphatase-1 was expressed and purified. The properties of the mutant enzyme were investigated in terms of its sensitivity toward several toxin inhibitors (okadaic acid, microcystin, nodularin, calyculin A, and cantharidic acid), as well as inhibitor-2. The mutant enzyme exhibited a gain of function in the form of a 10-fold increased sensitivity toward okadaic acid that suggests this region is involved in toxin binding. Significant changes in sensitivity to inhibitor-2 and several of the other toxins were also observed, indicating that these may have a common binding region. PMID- 8006005 TI - 8-Anilino-1-naphthalenesulfonate is a fluorescent probe of conformational changes in the D-galactose-H+ symport protein of Escherichia coli. AB - The binding of sugars and antibiotics to the overexpressed D-galactose-H+ symport protein (GalP) can be monitored from changes in the fluorescence of 8-anilino-1 naphthalenesulfonate (ANS) equilibrated with inside-out vesicles. Transported sugars, such as D-glucose and D-galactose, cause an enhancement in the ANS fluorescence of up to 13%. Nontransported sugars that have little, if any, affinity for GalP, such as L-galactose and L-glucose, have no effect upon the ANS fluorescence. Cytochalasin B and forskolin, which are potent inhibitors of the transporter, produce little change in the fluorescence, but are capable of reversing the D-galactose/D-glucose enhancement in fluorescence. Sugars that bind to GalP but are not transported, such as methyl-beta-D-glucose, produce only a slight quench in the ANS fluorescence, but again reverse the enhancement in fluorescence induced by transported sugars. A simple interpretation is that the increase in ANS fluorescence is attributable to the sugar-induced reorientation of the transporter from an inward- to an outward-facing conformation. Nontransported sugars and antibiotics, which are thought to bind at the inner membrane face of the transporter, are able to reverse the fluorescence enhancement by binding to the inward-facing conformation. The postulated reorientation process was sufficiently slow to follow its progress by stopped flow fluorometry. The Kd for the binding of D-galactose to the inward-facing site was 7.22 (+/- 1.49) mM, and the rate constants for outward and inward reorientation of the transporter were 4.06 (+/- 0.16) s-1 and 1.36 (+/- 0.18) s 1, respectively. The overall Kd values for a range of sugars and antibiotics have been determined, and the involvement of each sugar hydroxyl group in the recognition and translocation processes has been assessed. PMID- 8006006 TI - Characterization and crystallization of recombinant pea cytosolic ascorbate peroxidase. AB - An Escherichia coli expression system has been developed for pea cytosolic ascorbate peroxidase (APX). The enzyme was expressed as a fusion product with the E. coli maltose-binding protein for rapid, affinity chromatography purification. Recombinant ascorbate peroxidase (rAPX) was purified by tryptic digestion to separate the maltose-binding protein from rAPX followed by three chromatographic steps. The purified rAPX protein demonstrated identical electrophoretic, enzymatic, and spectral properties when compared to native APX isolated from pea shoots. Upon addition of an equal molar amount of H2O2, rAPX exhibits an initial decrease in the Soret maximum, which slowly converts to a stable, red-shifted Soret peak similar to that observed for cytochrome c peroxidase Compound I, indicating that rAPX Compound I consists of an oxyferryl (Fe(4+)-O) center. rAPX has been crystallized in a form suitable for crystal structure determination, and a preliminary set of native data to 2.6 A have been collected. PMID- 8006007 TI - Identification of three catalytic triad constituents and Asp-225 essential for function of lysine-specific serine protease, Achromobacter protease I. AB - Achromobacter protease I is a lysine-specific serine protease that Achromobacter lyticus M497-1 extracellularly secretes. The structural aspects necessary for the protease to function were investigated by means of site-directed mutagenesis to identify the constituents of the catalytic triad and the amino acid residue responsible for lysine specificity. The precursor molecules, which were produced by substitution of His-57, Asp-113, or Ser-194 for alanine, could not be converted to the mature form. In contrast, a precursor of a mutant in which either His-56 or Ser-193 is converted to alanine was perfectly processed autocatalytically and attained full protease activity. Substitution of Glu-190, one of the two candidates for determining lysine specificity, to glutamine, aspartic acid, or leucine had no or little effect on both proteolytic activity and substrate specificity. However, the kinetic parameters were subtly different from one another, depending on the nature of substituents in these mutants. The substitution of the other candidate, Asp-225, for asparagine or leucine resulted in the failure of maturation to the active forms. However, the precursor of the D225E mutant slowly matured and was essentially inactive. The observed reduction of protease activity is largely due to a decrease in the affinity of lysine to the protease. These results suggest that His-57, Asp-113, and Ser-194 are the three constituents of the catalytic triad in Achromobacter protease I and that Asp-225 plays a critical role in restricted substrate specificity as a lysyl endopeptidase. PMID- 8006008 TI - The macromolecular state of the transcription factor E2F and glucocorticoid regulation of c-myc transcription. AB - Glucocorticoids inhibit transcription of the proto-oncogene c-myc in lymphoid cells of thymic origin. To determine if this effect is associated with changes in the properties of the transcription factor E2F, extracts were prepared from control and glucocorticoid-treated P1798 murine T lymphoma cells, and the macromolecular state of E2F was assessed by gel-mobility shift. Control extracts exhibit two predominant gel-mobility shift entities of which one corresponds to "free" E2F. A second entity, complex C, has properties similar to those described for the complex containing E2F, p107, cyclin A, and Cdk2. Complex C disappears after addition of dexamethasone and is replaced by complex D. The mobility of this complex and its sensitivity to SV40 T antigen suggest that complex D corresponds to an E2F-p105Rb-1 complex. Extracts from control and glucocorticoid treated cells yield identical DNase I protection patterns on the c-myc P2 promoter. Furthermore, such extracts transcribe the c-myc P2 promoter in vitro with equal activity. The relative abundance of the E2F complexes was measured after addition of dexamethasone. Complex C disappears as cells withdraw from S phase, and complex D appears at this time. The genes encoding thymidine kinase (Tk-1) and p34cdc2 (cdc2) are regulated with kinetics similar to those observed for changes in the macromolecular state of E2F. However, regulation of c-myc expression occurs long before any change in E2F. The macromolecular state of E2F may regulate expression of genes at the G1/S boundary. However, the data are not consistent with the hypothesis that association of E2F with tumor suppressor gene products such as p107 or p105Rb-1 is relevant to glucocorticoid regulation of c myc transcription. PMID- 8006009 TI - Binding of reovirus to receptor leads to conformational changes in viral capsid proteins that are reversible upon virus detachment. AB - A conformational change was detected in reovirus upon its attachment to mouse L fibroblasts. Specifically, the capsid proteins of cell-bound virions became more resistant to pepsin digestion. Similar observations were made using glutaraldehyde-fixed cells or plasma membranes instead of live cells, indicating that virus internalization was not necessary for this effect. This conformational change was totally reversible, since bound virions reverted back to the pepsin sensitive state upon release from the cell surface. Not unexpectedly, a conformational change was also detected in the reovirus cell attachment protein sigma 1 when it alone bound to cells. The alteration was mapped, by deletion mutagenesis, to a region proximal to the N-terminal (virion-anchoring) end of the protein and was also found to be reversible. Structural changes in sigma 1 were also detectable following its interaction with sialic acid (conjugated to bovine serum albumin) shown previously to the minimal receptor determinant recognized by reovirus. These results suggest that upon cell attachment, a signal is transmitted from the C-terminal receptor-binding region of sigma 1 to the N terminus in a ripple-like progression that eventually leads to conformational changes in the other reovirus capsid proteins. An altered conformational state may be necessary for subsequent viral entry and programmed disassembly of viral capsids inside susceptible cells. PMID- 8006010 TI - Cross-species receptor binding characteristics of human and mouse leukemia inhibitory factor suggest a complex binding interaction. AB - Leukemia inhibitory factor (LIF) is a pleiotropic cytokine whose activities appear to be mediated through a single heterodimeric receptor complex. Human LIF (hLIF) can bind to and activate mouse LIF (mLIF) receptors but mLIF is unable to bind to hLIF receptors. Cross-species competition of mLIF and hLIF for binding to the mLIF receptor was found to be dependent on which ligand was used as the radioactive tracer (Layton, M. J., Cross, B. A., Metcalf, D., Ward, L. D., Simpson, R. J., and Nicola, N. A. (1992) Proc. Natl. Acad. Sci. U. S. A. 89, 8616 8620), and this phenomenon was investigated in the present study. We found that hLIF bound to the low affinity mLIF receptor with a 100-500-fold higher primary affinity and lower kinetic dissociation rate than mLIF, but both ligands displayed a single rate of ligand dissociation. In contrast, the binding of hLIF to low and high affinity hLIF receptors revealed two classes of binding site. The observed tracer-dependent phenomena suggested that both mLIF and hLIF interfere with the binding of each other to the mLIF receptor. A model is presented in which hLIF binds to two sites on mLIF and hLIF receptors, one of which interferes with the common site for mLIF. This model may reconcile some of the observed complexities of LIF/LIF receptor interactions. PMID- 8006011 TI - Herpes simplex virus glycoprotein D acquires mannose 6-phosphate residues and binds to mannose 6-phosphate receptors. AB - Herpes simplex viruses (HSV) use multiple and sequential receptors to enter host cells. HSV glycoprotein D (gD) has been implicated in binding to cellular receptors that facilitate virus penetration into cells. We used soluble forms of gD that were expressed in Chinese hamster ovary cells to characterize and identify a putative cellular receptor for HSV as the 275-kDa mannose 6 phosphate/insulin-like growth factor II receptor. Soluble gD also bound to the 46 kDa cation-dependent mannose 6-phosphate (Man-6-P) receptor and was extensively modified with Man-6-P residues on its Asn-linked oligosaccharides. Additionally, soluble gD was a high affinity substrate for N-acetylglucosamine-1 phosphotransferase, the first enzyme in the biosynthetic pathway for the addition of Man-6-P residues to lysosomal enzymes. The membrane form of gD immunoprecipitated from HSV-infected cells also bound to the 275-kDa mannose 6 phosphate/insulin-like growth factor II receptor, albeit poorly, and only a small fraction of the membrane gD was modified with Man-6-P. Notwithstanding this low level of mannose phosphorylation, the interaction between gD and Man-6-P receptors may play a role in some aspect of virus entry or egress. PMID- 8006012 TI - Hepatocyte nuclear factor-1 alpha (HNF-1 alpha) and HNF-1 beta regulate transcription via two elements in an intestine-specific promoter. AB - Hepatocyte nuclear factor-1 alpha (HNF-1 alpha) and HNF-1 beta are transcription factors that contain a divergent homeodomain, bind to DNA as homo- or heterodimers, and act to regulate transcription of many genes that are expressed primarily in liver. We show that HNF-1 alpha and HNF-1 beta act as regulatory factors for transcription of sucrase-isomaltase (SI), the gene for which is expressed exclusively in absorptive enterocytes of the small intestine. HNF-1 alpha and HNF-1 beta bind to two evolutionarily conserved sites in the SI promoter, previously named SIF2 and SIF3, with different relative affinities. HNF 1 alpha binds to the SIF3 element with greater affinity than to the SIF2 element, whereas HNF-1 beta binds to both elements equally. Co-transfection experiments demonstrated that HNF-1 alpha is able to increase transcriptional initiation from a minimal SI intestine-specific promoter. In contrast, HNF-1 beta has no functional effect on transcription of the SI promoter. The functional and DNA binding differences of HNF-1 alpha and HNF-1 beta on elements in the SI promoter suggest that these transcription factors may play a role in the complex spatial patterns of SI gene expression in the intestine. PMID- 8006014 TI - Background Ca2+ influx mediated by a dihydropyridine- and voltage-insensitive channel in pancreatic beta-cells. Modulation by Ni2+, diphenylamine-2 carboxylate, and glucose metabolism. AB - A stepwise increase in extracellular Ca2+ concentration ([Ca2+]o) can evoke insulin release from pancreatic islets in the absence of secretagogues. We have investigated the ionic mechanism underlying this secretory response by recording intracellular free Ca2+ concentration ([Ca2+]i) from single mouse islets of Langerhans using ratiometric fura-2 microfluorometry. In the presence of 11 mM glucose, the [Ca2+]i undergoes fast oscillations associated with bursting electrical activity. Nifedipine (10 microM) suppressed these oscillations and markedly lowered the [Ca2+]i. Raising the [Ca2+]o from 2.56 to 12.8 mM in the continued presence of 11 mM glucose and nifedipine evoked pronounced [Ca2+]i rises of variable amplitude and time course. This effect was dose-dependent (EC50 = 3.6 mM) and remained essentially unchanged in the absence of glucose or in the presence of 3 mM glucose and nifedipine, conditions where beta-cells are hyperpolarized by approximately -25 mV. Depleting the acetylcholine-mobilizable internal Ca2+ pools by repetitively challenging the islets with acetylcholine in the absence of Ca2+ actually potentiated the standard high Ca2+ responses. The latter were strongly reduced by millimolar concentrations of Ni2+ (70% reduction at 3 mM) and by diphenylamine-2-carboxylate (DPC; IC50 = 145 microM), a blocker of nonselective cation channels. The standard high Ca2+ responses were relatively insensitive to the glycolytic inhibitor mannoheptulose. It is proposed that the high Ca(2+)-evoked [Ca2+]i responses are primarily accounted for by Ca2+ influx through dihydropyridine- and voltage-insensitive, nonselective cation channels. These channels do not appear to be under the control of glucose metabolism. Although their function is unknown, they may be essential to supplying the beta cells with Ca2+ in the absence of stimulatory levels of fuel secretagogues. PMID- 8006013 TI - Replication of bovine papillomavirus type 1 origin-containing DNA in crude extracts and with purified proteins. AB - The in vitro replication of DNA containing the bovine papillomavirus (BPV-1) origin has been carried out with cell-free extracts from mouse FM3A and human HeLa cells. DNA synthesis required the E1 protein, the minimal origin of replication (nucleotides 7911-22 of the BPV-1 genome), and, at low levels of FM3A extract, the addition of the human single-stranded DNA-binding protein (also called RP-A or RF-A). The E2 protein was not absolutely required, but could stimulate DNA synthesis at low levels of E1. DNA synthesis was also reconstituted using purified proteins from HeLa cells. These protein factors included human single-stranded DNA-binding protein, topoisomerase I, and DNA polymerase (pol) alpha-primase complex. At low concentrations of pol alpha-primase complex, the formation of high molecular weight products was dependent on the addition of DNA polymerase delta holoenzyme containing proliferating cell nuclear antigen and activator 1, also called RF-C. We have overexpressed and isolated the E1 protein from bacteria. This protein also supported BPV DNA synthesis, both in crude extracts and with purified proteins suggesting that E1 phosphorylation is not required for BPV DNA replication in vitro. PMID- 8006015 TI - Crystal structures, spectroscopic features, and catalytic properties of cobalt(II), copper(II), nickel(II), and mercury(II) derivatives of the zinc endopeptidase astacin. A correlation of structure and proteolytic activity. AB - The catalytic zinc ion of astacin, a prototypical metalloproteinase from crayfish, has been substituted by Co(II), Cu(II), Hg(II), and Ni(II) in order to probe the role of the metal for both catalysis and structure. Compared to Zn(II) astacin, Co(II)- and Cu(II)-astacin display enzymatic activities of about 140 and 37%, respectively, while Ni(II)- and Hg(II)-astacin are almost inactive. The electron paramagnetic resonance spectrum of Cu(II)-astacin is typical of 5-fold coordinated copper(II), and its intense absorption maxima at 445 and 325 nm are probably due to ligand-metal charge-transfer transitions involving Tyr-149. This residue had been identified previously by x-ray crystallography of the zinc enzyme as a zinc ligand, in addition to three imidazoles and a glutamic acid bound water molecule. We present now the refined high-resolution x-ray crystal structures of Cu(II)-, Co(II)-, and Ni(II)-astacin, which exhibit a virtually identical protein framework to the previously analyzed structures of Zn(II)-, apo , and Hg(II)-astacin. In Co(II)- and Cu(II)-astacin, the metal is penta coordinated similarly to the native zinc enzyme. In the Ni(II) derivative, however, an additional solvent molecule expands the metal coordination sphere to a distorted octahedral ligand geometry, while in Hg(II)-astacin, no ordered solvent molecule at all is observed in the inner coordination sphere of the metal. This indicates a close correlation between catalytic properties and ground state metal coordination of astacin. PMID- 8006016 TI - Molecular cloning and identification of a rat serum carboxylesterase expressed in the liver. AB - We have cloned and sequenced a carboxylesterase from rat liver and purified the corresponding protein from rat blood. The cDNA encodes the entire mature serum esterase protein. It is apparently identical to cDNAs cloned from rat liver by several groups (Long, R. M., Satoh, H., Martin, B. M., Kimura, S., Gonzales, F. J., and Pohl, L. R. (1988) Biochem. Biophys. Res. Commun. 156, 866-873; Takagi, Y., Morohashi, K.-i., Kawabata, S.-i., Go, M., and Omura, T. (1988) J. Biochem. (Tokyo) 104, 801-806; and Robbi, M., and Beaufay, H. (1992) Biochem. Biophys. Res. Commun. 183, 836-841). However, the identification of the protein encoded by this cDNA has not been previously reported. The COOH-terminal -TEHT sequence found in the rat serum carboxylesterase does not possess retention properties and is therefore responsible for its secretion and presence in the circulation. The rat serum carboxylesterase was purified to apparent homogeneity by affinity chromatography on immobilized antibody to rat liver microsomal acyl-CoA thioesterase followed by ion exchange chromatography. The purified protein, with a M(r) of approximately 70,000, was cleaved in situ in a polyacrylamide gel with trypsin, and two peptides were isolated and sequenced. Sequence analysis showed that both peptides were identical only to the corresponding deduced amino acid sequence of the cloned cDNA. Antibodies raised to the COOH-terminal amino acid sequence deduced from the cDNA cross-reacted with the purified rat serum carboxylesterase. Changes in serum esterase activity levels followed changes in protein mass in rat serum and changes in liver mRNA levels in response to various nutritional conditions while total liver esterase activity was essentially unchanged. The above experiments confirm the identity of the protein isolated from rat sera with the cDNA cloned from rat liver and suggest a function for the serum esterase in lipid metabolism. PMID- 8006017 TI - Interleukin-1 beta regulates human cytotrophoblast metalloproteinase activity and invasion in vitro. AB - During early human pregnancy, fetal cytotrophoblasts rapidly invade the uterus. This process has many similarities to tumor invasion, except that the extent and the timing of cytotrophoblast invasion are carefully regulated. Therefore, this system is particularly useful for studying mechanisms that regulate invasive processes. Previously, we showed that production and activation of the 92-kDa type IV collagenase (matrix metalloproteinase(MMP)-9) is necessary for cytotrophoblast invasion in vitro. In other systems, interleukin (IL)-1 beta is an important regulator of matrix-degrading metalloproteinases. Therefore, we investigated trophoblast production of IL-1 beta and its receptors, as well as the effects of this cytokine on cytotrophoblast metalloproteinase activity and invasion. The results showed that release of IL-1 beta parallels the invasive potential of the cytotrophoblasts; the highest levels are produced by first trimester cells and the lowest levels by term cells. Immunoprecipitation showed that cytotrophoblasts express the 80-kDa type I IL-1 receptor, suggesting that autocrine effects are possible. IL-1 beta stimulated trophoblast MMP-9 secretion (by a mechanism that required nascent mRNA and protein synthesis) as well as metalloproteinase activity and invasion of Matrigel. Increasing (by lipopolysaccharide treatment) or decreasing (by glucocorticoid treatment) IL-1 beta production had parallel effects on MMP-9 secretion, metalloproteinase activity, and invasion. Because IL-1 beta and corticosteroids are present in high concentrations at the maternal-fetal interface, normal trophoblast invasion may be regulated, in part, by their opposing actions. In contrast, stimulation of cytotrophoblast IL-1 beta secretion by lipopolysaccharide may play a role in the sequela of infected fetal membranes. PMID- 8006018 TI - Antagonists inactivate the inositol 1,4,5-trisphosphate (Ins-1,4,5-P3)-dependent Ca2+ channel independent of Ins-1,4,5-P3 metabolism. AB - Streptolysin O-permeable pancreatic acini, which retain intact signaling systems, were used to study the regulation of the inositol 1,4,5-trisphosphate (Ins-1,4,5 P3)-activated Ca2+ channel during agonist stimulation and antagonist inhibition. Stimulation of permeable cells with carbachol induced rapid Ca2+ release from internal stores. Addition of heparin prior to or after agonist stimulation inhibited the release, indicating the activation of the Ins-1,4,5-P3-dependent Ca2+ channels by the agonist. Termination of cell stimulation with the specific antagonist atropine rapidly inactivated the release channels. Channel inactivation by the antagonist was independent of Ins-1,4,5-P3 levels since (a) addition of atropine to carbachol-stimulated cells resulted in a slow hydrolysis of Ins-1,4,5-P3, (b) addition of 10-fold excess Ins-1,4,5-P3 together with the agonist did not prevent channel inactivation by the antagonist, and (c) the antagonist inactivated Ca2+ release in the presence of saturating concentration of the nonhydrolyzable Ins-2,4,5-P3. Hence, the antagonist appears to stabilize the Ins-1,4,5-P3-activated Ca2+ channel in a state refractory to Ins-1,4,5-P3. These findings are the first direct evidence that the channel can exist in such a refractory state. PMID- 8006019 TI - The high mobility group protein HMG1 can reversibly inhibit class II gene transcription by interaction with the TATA-binding protein. AB - Regulation of transcription by RNA polymerase II in eukaryotic cells requires both basal and accessory factors, which interact through specific protein-DNA or protein-protein interactions. The high mobility group 1 protein (HMG1) was previously demonstrated to be a nonhistone chromatin-associated protein, which selectively recognizes cruciform DNA rather than a specific primary sequence element. During our investigations of proteins that interact with TFIID, we found that purified mammalian HMG1, as well as recombinant human HMG1, can interact with TATA-binding protein (TBP) in the presence of a TATA box-containing oligonucleotide to form a specific HMG1.TBP.promoter complex. This complex prevents TFIIB binding to TBP and consequently blocks formation of the preinitiation complex. In contrast, TFIIA can compete with HMG1 for binding to TBP. In an in vitro transcription assay reconstituted with highly purified or recombinant general factors, HMG1 is able to inhibit transcription by RNA polymerase II over 30-fold. As expected, addition of TFIIA can partially reverse this repression in a concentration-dependent manner. These results demonstrate that HMG1, a chromatin-associated protein, has the potential to act as a TBP dependent negative transcription factor and may provide an important link between chromatin structure and the modulation of class II gene transcription. PMID- 8006020 TI - Production and characterization of recombinant Goodpasture antigen in insect cells. AB - The Goodpasture antigen is the target of anti-basement membrane autoantibodies in Goodpasture's disease, a severe human autoimmune disease characterized by glomerulonephritis and lung hemorrhage. It has been identified as the NC1 domain of the alpha 3 chain of type IV collagen (alpha 3(IV)NC1), a minority component of glomerular basement membrane (GBM). Protocols for obtaining pure human antigen are laborious and low yielding and require cadaver kidneys. Recombinant alpha 3(IV)NC1 produced in Escherichia coli has been insoluble and poorly recognized by patients' autoantibodies. We have used the baculovirus expression system to produce the antigen as a soluble product in Sf9 cells. A transfer vector was constructed from cDNAs encoding the leader peptide, NH2 terminus, and 7 S domain of the human alpha 1 chain of type IV collagen and was joined inframe to the NC1 domain and COOH terminus of the human alpha 3 chain under the control of the polyhedrin promoter. It therefore encodes a hybrid "mini"-collagen chain from which the majority of the central triple helical region has been deleted. The recombinant antigen was seen on SDS-polyacrylamide gel electrophoresis and Western blots of supernatants at its predicted molecular size of 41 kDa and as dimers of 82 kDa. It reacted strongly with human autoantibodies by Western blotting and enzyme-linked immunosorbent assay, inhibited binding of autoantibodies to human GBM, and bound two monoclonal antibodies known to recognize human alpha 3(IV)NC1. A common alternatively spliced variant alpha 3(IV)NC1 mRNA, leading to a truncated NC1 domain of 60 amino acids, was expressed as a fusion protein with the same alpha 1 NH2-terminal sequence. It failed to be exported from the cell and was not recognized by autoantibodies. Other NC1 domains could be expressed in the same way. These recombinant molecules should prove invaluable for the in vitro study of the immunopathogenesis of Goodpasture's disease, and the approach provides a means by which interactions between the different type IV collagen chains found in GBM could be studied in vitro. PMID- 8006021 TI - Superoxide-dependent hydroxylation by myeloperoxidase. AB - When stimulated, neutrophils undergo a respiratory burst converting oxygen to superoxide. Although superoxide is critical for microbial killing by phagocytic cells, the precise role it plays has yet to be established. It has been proposed to optimize their production of hypochlorous acid and to be required for the generation of hydroxyl radicals. Superoxide is also involved in the hydroxylation of salicylate by neutrophils. However, the mechanism of this reaction is unknown. We found that neutrophils stimulated with opsonized zymosan hydroxylated salicylate to produce mainly 2,5-dihydroxybenzoate. Its formation was dependent on superoxide and a heme protein but was independent of hydrogen peroxide and hydroxyl radicals. Production of 2,5-dihydroxybenzoate was enhanced by methionine, which scavenges hypochlorous acid. Neutrophils from an individual with myeloperoxidase deficiency hydroxylated salicylate at only 13% of the level of control cells. Purified human myeloperoxidase and xanthine oxidase plus hypoxanthine hydroxylated salicylate to produce 2,5-dihydroxybenzoate. As with neutrophils, the reaction required superoxide but not hydrogen peroxide and was unaffected by hydroxyl radical scavengers. Thus, myeloperoxidase catalyzes superoxide-dependent hydroxylation. This newly recognized reaction may be relevant to the in vivo functions of superoxide and myeloperoxidase. PMID- 8006022 TI - Subtle differences in human pregnancy-specific glycoprotein gene promoters allow for differential expression. AB - Eleven pregnancy-specific glycoprotein (PSG) genes reside on human chromosome 19. The sequence of these genes is extremely similar and that similarity extends to their putative control regions. However, the expression pattern of each PSG gene differs in the placenta, the primary site of PSG synthesis. To understand the molecular mechanisms underlying differential PSG expression, we characterized promoter elements of six PSG genes. We have shown previously that nucleotides 172 to -34 with respect to the translation start site constitute a minimal promoter in the PSG12 gene (class 1). We now show that PSG1-I and PSG3 are also members of class 1 genes. In contrast, only nucleotides -172 to -80 are necessary for promoter activity in PSG5, PSG6, and PSG11 genes (class 2). Class 2 genes contain a perfect Sp1 recognition sequence (CCCCGCCC) at nucleotides -148 to -141 which is necessary for promoter activity. Placental cell extracts formed three protein-DNA complexes with nucleotides -172 to -80 of all six PSG genes. One of the components of these complexes is an Sp1-like molecule. We have previously reported activator sequences within nucleotides -83 to -34 in PSG12. We now show that a 50-kDa protein binds to this region of PSG12, and the resultant complex can be supershifted by a monoclonal antibody to PEA3. PMID- 8006023 TI - Evidence for discrete diacylglycerol and phorbol ester activator sites on protein kinase C. Differences in effects of 1-alkanol inhibition, activation by phosphatidylethanolamine and calcium chelation. AB - Stimulation of protein kinase C (PKC) activity is achieved in vivo by diacylglycerol but can also be obtained with tumor-promoting phorbol esters. Evidence is presented indicating that these two classes of activator may interact at different regions of the enzyme. The activity of a calcium-dependent PKC isoform (PKC-I) preparation was determined using 1,2-dioleoylglycerol (DOG) together with the phorbol ester 4 beta-12-O-tetradecanoylphorbol-13-acetate (TPA). The resulting PKC activity was in excess of that attained with either activator alone, each being at a maximum concentration for activation. A similar result was obtained with purified PKC-alpha and -epsilon isoforms, indicating that the additive effect was not due to sites being on distinct enzyme molecules. Support for two dissimilar activator sites came from the observation that the inactive phorbol ester 4 alpha-TPA competed for TPA but not for DOG in PKC activation. Other differences were observed between TPA- and DOG-activated PKC. It was found that 1-butanol inhibited DOG-activated PKC-I, while being without effect on stimulation by TPA. Also, the inclusion of phosphatidylethanolamine in the lipid vesicles led to a potentiation of PKC-I activity which was greater when activation was achieved by DOG compared to TPA. Further, the calcium- and DOG dependent active conformational change of PKC was fully reversible upon calcium chelation, while that stimulated by TPA was only partially reversible. These experiments taken together suggest that diacylglycerols and phorbol esters bind with different affinities and at different sites on PKC, and induce distinct activated conformational forms of the enzyme. PMID- 8006024 TI - Poly(A) binds to initiation factors and increases cap-dependent translation in vitro. AB - Both the 5' cap (m7GpppN) and the 3' poly(A) tail of eukaryotic mRNAs are important regulators of translation efficiency in vivo. Their function, however, is markedly reduced in in vitro translation systems derived from either rabbit reticulocytes or wheat germ. The impact of exogenous poly(A) on cap-dependent translation was examined in vitro. The translation of uncapped mRNA was preferentially repressed in the presence of exogenous poly(A). As a result, translation became increasingly cap-dependent with the increase in exogenous poly(A). The translation in wheat germ lysate was stimulated by the addition of purified eukaryotic initiation factor (eIF)-4B or eIF-4F; however, addition of poly(A) prevented this eIF-4B- or eIF-4F-mediated stimulation. Addition of eIF-4F or eIF-4B, alone, was not sufficient to restore translation in lysate to which poly(A) had been added. Restoration, however, was observed when eIF-4F, eIF-4B, and eIF-4A were added in combination. These data suggest that 1) exogenous poly(A) may bind to and sequester factors required for translation and 2) that capped messages compete with poly(A) more efficiently for these factors than do uncapped mRNAs. Gel shift analysis of purified initiation factors isolated from wheat germ confirmed that eIF-4B and eIF-4F do in fact form complexes with poly(A) in vitro. PMID- 8006025 TI - Kinetic analysis of the trafficking of muscarinic acetylcholine receptors between the plasma membrane and intracellular compartments. AB - We have studied the kinetics of muscarinic receptor trafficking between the plasma membrane and intracellular compartments in NG108-15 cells. A model of trafficking is proposed that includes four transport steps, delivery to the plasma membrane from the Golgi complex (linear) and endosomes (exponential) internalization from the plasma membrane into endosomes (exponential), and a degradative route from endosomes into lysosomes (linear). Based upon this model, a general equation has been derived that describes changes in receptor number at the plasma membrane and in endosomes in response to agonist stimulation. By following the movement of receptors into and out of the plasma membrane under various experimental conditions, it has been possible to determine the values of the four rate constants in the general equation and also the size of the endosomal receptor pool created by agonist stimulation. The consequences of changes in these constants for receptor trafficking are demonstrated. The model accounts for the effect of varying the duration of agonist stimulation on the size of the endosomal receptor pool and also permits an estimation of the receptor trafficking that underlies the well-established phenomenon of agonist induced receptor internalization. PMID- 8006026 TI - Biosynthesis and processing of the cell adhesion molecule PECAM-1 includes production of a soluble form. AB - PECAM-1 (CD31) is a 130-kDa glycoprotein found on platelets, endothelial cells, granulocytes, and monocytes, as well as on certain myelomonocytic cell lines. Recent studies have shown that PECAM-1 may be involved in activation of leukocyte integrins and may also be involved in adhesive interactions of circulating leukocytes and the vessel wall. In spite of the important functional role that PECAM-1 plays in these processes, little is known about the biosynthesis, processing, and turnover of PECAM-1 on the cell surface. We have studied the biosynthesis of PECAM-1 in the promonocytic cell line U937, and in endothelial cells, by pulse-chase labeling and immunoprecipitation. PECAM-1 was synthesized as a 110-kDa precursor form, which was processed into the 130-kDa mature form within 1-3 h, during which time it began to move to the cell surface. The protein disappeared from the cell surface in both cell types about 48 h after labeling. A soluble form of PECAM-1, which is 5-10 kDa smaller than cell-associated PECAM-1 and contains the cytoplasmic tail, was observed in the culture media of HUVECs and phorbol ester-treated U937 cells. This form of soluble PECAM-1 is encoded by an alternatively spliced mRNA from which the exon containing the transmembrane domain has been removed. Soluble PECAM-1 was also detected in normal human plasma at levels of 10-25 ng/ml. Two isoforms of plasma PECAM-1, which differed in the presence of the cytoplasmic tail, were observed by Western blot analysis. In parallel with soluble forms of other cell adhesion molecules, soluble PECAM-1 may play a role in modulating the inflammatory response. PMID- 8006027 TI - Assembly of amino-terminal fibronectin dimers into the extracellular matrix. AB - Fibronectin is a dimeric adhesion molecule that consists of three types of repeating modules. Adherent cells bind soluble fibronectin and incorporate it into insoluble fibrils in the extracellular matrix. The amino-terminal 70-kDa portion of fibronectin mediates binding to the cell surface, but amino-terminal fragments do not accumulate in the extracellular matrix. The ninth type I and first type III modules, the cell adhesion region, and the cysteines that form the interchain disulfide bonds have also been implicated in matrix assembly. To further define which regions of fibronectin are essential for matrix assembly, we generated a dimeric protein (d70 kDa) in which the 70-kDa amino terminus is directly linked to the last 51 amino acids of fibronectin, which contain the cysteines involved in interchain disulfide bonding. d70 kDa bound to cells and accumulated in the extracellular matrix. Incorporation of d70 kDa into the extracellular matrix was dependent upon protein synthesis; in cycloheximide treated cultures that lacked a pre-existing matrix, d70 kDa accumulated in the extracellular matrix only in the presence of intact fibronectin. Monomeric 70-kDa protein was not incorporated into the matrix in the presence or absence of cycloheximide. These data indicate that fibronectin molecules containing only the amino-terminal 70-kDa region and the carboxyl-terminal 51 amino acids can become assembled into the extracellular matrix. PMID- 8006028 TI - Regulation of protease nexin-1 target protease specificity by collagen type IV. AB - Recent studies have shown that serine protease inhibitors can be regulated in their activity, specificity, and location by glycoprotein or extracellular matrix (ECM) co-factors. Protease nexin-1 (PN-1) is a member of the serpin superfamily of serine protease inhibitors which can rapidly inhibit thrombin, urokinase, and plasmin. PN-1 binds tightly to and is regulated by the ECM. This interaction accelerates the inhibition of thrombin by PN-1 and blocks urokinase and plasmin inhibition by PN-1. Previous work showed that heparan sulfate proteoglycan is largely responsible for the acceleration of thrombin inhibition by PN-1. Our current studies were directed at identifying ECM component(s) that decreased the ability of PN-1 to inhibit urokinase and plasmin. These studies showed that collagen type IV decreased the formation of SDS-stable complexes between urokinase or plasmin and PN-1 without affecting formation of complexes between thrombin and PN-1. The second order rate constant for inhibition of urokinase by PN-1 was markedly decreased with increasing collagen type IV, whereas the second order rate constant for inhibition of thrombin by PN-1 was unaffected by addition of collagen type IV. Other ECM components (collagen type I, vitronectin, fibronectin, and heat-denatured collagen type IV) did not affect complex formation or the rate of inhibition of proteases by PN-1, indicating that these effects were specific to collagen type IV. Binding of PN-1 to immobilized collagen type IV was demonstrated using an enzyme-linked immunosorbent assay; the concentration of PN-1 necessary to obtain 50% saturation of the immobilized collagen type IV binding sites was approximately 15 nM. Collagen type IV was also copurified with PN-1 from fibroblast-conditioned medium. These results demonstrate a novel regulation of serpin specificity in which an ECM co-factor decreased the inhibition of certain proteases by the serpin without affecting the inhibition of its target protease. PMID- 8006029 TI - Primary structure and distribution of ryanodine-binding protein isoforms of the bullfrog skeletal muscle. AB - We have cloned two groups of cDNAs which encode isoforms of ryanodine-binding protein/Ca2+ release channel of the bullfrog skeletal muscle sarcoplasmic reticulum. One of the cDNA groups encodes the protein of 5,037 (or 5,031 with a deletion) amino acids with a molecular weight of 571,262 (or 570,607), which is identified as the alpha-isoform of the ryanodine-binding protein based on the amino acid sequence of three tryptic fragments of the purified protein. The other group of cDNAs encodes the protein of 4,868 amino acids with molecular weight of 553,029, which contains the sequences of three proteolytic fragments derived from the beta-isoform protein. About 70% of the amino acid sequence identity is present between alpha- and beta-isoforms of the bullfrog. The primary structure of the alpha-isoform is highly (80%) homologous to the ryanodine-binding protein cloned from rabbit skeletal muscle (type 1). The beta-isoform, on the other hand, is more than 85% identical with that from the rabbit brain (type 3), while it has only 67% overall identity with type 1. Analyses of RNA from various tissues of the bullfrog demonstrate that the beta-isoform is widely expressed, while the alpha-isoform is expressed mainly in skeletal muscle. A phylogenetic analysis of the ryanodine-binding protein/Ca2+ release channel family suggests that the various types of Ca2+ release channels have evolved from an ancestor gene. Possible differential roles of alpha- and beta-isoforms of ryanodine-binding protein in Ca2+ release mechanisms including skeletal muscle excitation contraction coupling were discussed. PMID- 8006030 TI - Zones of exocytotic release on bovine adrenal medullary cells in culture. AB - Secretion of catecholamines from individual bovine adrenal medullary cells in culture was examined by amperometry with 1-micron radius carbon-fiber electrodes. Vesicular secretion is observed as a series of current spikes upon exposure to a secretagogue. The small size of the electrodes was exploited to map exocytotic release sites on the surface of bovine adrenal medullary cells. These studies reveal for the first time that release sites are spatially localized on endocrine cells in culture for a time scale of at least 15 min. Fluorescent monitoring by confocal microscopy of deposition of dopamine-beta-hydroxylase from the vesicular membrane into the plasma membrane during exocytosis confirms the existence of zones of exocytotic inactivity on the surface of the cell. Measurement of coincident spikes with two adjacent electrodes (2.5-microns radius) has allowed the spatial resolution for measurement of exocytosis to be defined as 2 microns from the projected circumference of the electrode on the surface of the cell. In this small domain, point-source release and diffusional broadening would result in narrow spikes (Schroeder, T. J., Jankowski, J. A., Kawagoe, K. T., Wightman, R. M., Lefrou, C., and Amatore, C. (1992) Anal. Chem. 64, 3077-3083), a feature not seen in the data. Thus, for adrenal medullary cells, release following vesicular fusion is not instantaneous, but is a prolonged event occurring over several milliseconds. PMID- 8006031 TI - Graded methylation in the promoter and body of the O6-methylguanine DNA methyltransferase (MGMT) gene correlates with MGMT expression in human glioma cells. AB - Expression of the O6-methylguanine DNA methyltransferase (MGMT) gene in human glioma cell lines is strongly associated with resistance to the chemotherapeutic agent 1,3-bis(2-chloroethyl)-1-nitrosourea. To examine the possibility that methylation of the body and promoter regions of the MGMT gene is associated with MGMT expression in a graded, rather than a completely on/off fashion, the present study analyzed the methylation status of the MGMT gene in human glioma cell lines exhibiting a wide range of MGMT expression. Methylation in the body of the gene was uniform within each cell line and correlated directly with MGMT expression. The level of MGMT promoter methylation was also graded across the cell lines, at 21 of 25 CpGs tested, but correlated inversely with MGMT expression. Two sites in the MGMT promoter were also much more accessible to restriction enzyme digestion, and thus in a more open chromatin conformation, in nuclei from high MGMT expressors relative to nuclei from cells with little or no MGMT expression. We conclude that the level of methylation, in both the body and promoter of the MGMT gene, is associated with MGMT expression in a graded fashion and may be important in setting the transcriptional state of the MGMT promoter through changes in chromatin structure. PMID- 8006032 TI - Changes in parathyroid hormone receptors during chondrocyte cytodifferentiation. AB - The purpose of this study was to investigate the relationship between changes in parathyroid hormone (PTH) receptor levels and chondrocyte maturation during endochondral ossification. Chondrocytes were isolated from the growth plate of rabbit ribs and maintained in the presence of 10% serum in mass cultures. Treatment with PTH-(1-84) and a PTH-(1-34) fragment suppressed the increases in alkaline phosphatase activity and in type X collagen and 1 alpha,25 dihydroxyvitamin D3 receptor levels and abolished 45Ca incorporation into mineral, all of which occurred in parallel untreated cultures in the hypertrophic (terminal) stage. These effects of PTH were observed at low concentrations (10( 10) to 10(-9) M) and within 24-48 h of treatment. PTH-(1-84) and PTH-(1-34) also increased [35S]sulfate incorporation into newly synthesized proteoglycans. In contrast, the middle and carboxyl-terminal fragments of PTH tested had little effect on proteoglycan synthesis or terminal differentiation. The binding of 125I PTH-(1-34) to cells in the growth plate was greater than that to cells in liver, skin, muscle, brain, or kidney. When the correlation between binding levels and stage of maturation was examined, we found that 125I-PTH-(1-34) binding to its 72 kDa receptor was low in resting and proliferating chondrocytes, increased 10-fold in matrix-forming chondrocytes, and thereafter decreased in hypertrophic chondrocytes both in vitro and in situ. Scatchard analysis revealed that the changes in PTH binding were due to changes in the number, and not in the affinity, of the receptor. The changes in PTH-(1-34) binding paralleled those in [35S]sulfate incorporation into proteoglycans. These findings suggest that stage dependent increases in PTH/PTH-related peptide receptor levels localize the hormone stimulation of proteoglycan synthesis and inhibition of precocious hypertrophy in the matrix-forming zone of growth plates. PMID- 8006033 TI - Study of the roles of proline 391 and a highly conserved sequence in the carboxyl terminal region of members of the serpin family in the secretion of alpha 1 proteinase inhibitor. AB - Truncation of alpha 1-proteinase inhibitor prior to Pro391 prevents its secretion. This residue is the carboxyl terminus of a highly conserved sequence in serpins, suggesting that either Pro391 or the conserved sequence may serve as at least a part of a signal recognized by components of the secretory pathway. To evaluate these possibilities, we have determined the effects of replacement of Pro391 on the secretion of alpha 1-proteinase inhibitor and have examined the ability of the 9-residue conserved sequence to mediate secretion. We find that replacement of Pro391 with hydrophobic residues yields variants that are well secreted, but replacement with other classes of amino acids severely restricts secretion. These results show that while alpha 1-proteinase inhibitor is secreted most efficiently when proline occupies position 391, Pro391 is not an absolute requirement for its secretion. Our results show that the 9-amino acid conserved sequence found near the carboxyl termini of proteins of the serpin family is not sufficient to direct the secretion of alpha 1-proteinase inhibitor. We conclude that mutations affecting residue 391 and other positions in the conserved region lead to structural changes, possibly very minor, that influence the secretion of alpha 1-proteinase inhibitor. PMID- 8006034 TI - Alternative mRNA splicing generates tissue-specific isoforms of 116-kDa polypeptide of vacuolar proton pump. AB - The cDNA encoding the 116-kDa polypeptide of the bovine brain vacuolar-type proton translocating ATPases has been cloned and sequenced. One of five clones differed from all others in that it contained an 18-base pair deletion within the coding region, whereas it was identical to the other clones in overlapping coding and noncoding regions, indicating that this heterogeneity arises through an alternative splicing mechanism. By conventional Northern analysis, only one 4.1 kilobase mRNA was identified in bovine brain, heart, kidney, liver, and spleen. However, a polymerase chain reaction-based analysis revealed two species of mRNA with a tissue-specific distribution. Type I, containing the 18-base pair insert, was found in brain, whereas the truncated (Type II) form was found in all tissues examined. Similar tissue distributions of rat mRNA were observed. The deletion site accounting for this variability occurs within a predicted protease sensitivity motif (PEST site), suggesting that differences in the biological half life of the two 116-kDa isoforms may exist. PMID- 8006036 TI - Primary sequence and immunological characterization of beta-subunit of high conductance Ca(2+)-activated K+ channel from smooth muscle. AB - The charybdotoxin receptor, purified from bovine tracheal smooth muscle, consists of two subunits (alpha and beta) and, when reconstituted into planar lipid bilayers, forms functional high conductance Ca(2+)-activated K+ channels. Amino acid sequence, obtained from proteolytic fragments of the beta-subunit, was used to design oligonucleotide probes with which cDNAs encoding this protein were isolated. The cDNAs encode a protein of 191 amino acids that contains two hydrophobic (putative transmembrane) domains and bears little sequence homology to subunits of other known ion channels. Site-directed antisera, raised against putative extracellular epitopes of this protein, specifically immunoprecipitated 125I-labeled Bolton-Hunter beta-subunit as well as [125I]charybdotoxin-cross linked beta-subunit. Under nondenaturing conditions, however, these anti-beta sera immunoprecipitated a complex consisting of both the alpha- and beta subunits. The data demonstrate that, in vivo, the high conductance Ca(2+) activated K+ channel exists as a multimer containing both alpha- and beta subunits, and this cDNA represents the first beta-subunit of a potassium channel cloned to date. Furthermore, we demonstrate that the cloned protein is the subunit to which charybdotoxin is specifically and covalently incorporated when cross-linked to the channel. PMID- 8006035 TI - Assignment of the membrane attachment, DNA binding, and transcriptional activation domains of sterol regulatory element-binding protein-1 (SREBP-1). AB - Transcription of the low density lipoprotein receptor gene and other sterol regulated genes is stimulated by sterol regulatory element-binding protein-1 (SREBP-1), a basic-helix-loop-helix-leucine zipper (bHLH-ZIP) transcription factor. Human SREBP-1 is synthesized as an 1147-amino acid precursor that is attached intrinsically to membranes of the nuclear envelope and endoplasmic reticulum. In sterol-depleted cells the precursor is cleaved to generate an NH2 terminal fragment that enters the nucleus and activates transcription by binding to sterol regulatory element-1 (SRE-1). Sterols prevent transcriptional activation by blocking the proteolytic cleavage. In the current studies, performed with hamster SREBP-1, we used mutational analysis to localize the transcriptional activation domain to an acidic NH2-terminal sequence. Deletion of this sequence converted SREBP-1 from an activator to an inhibitor of transcription. DNA binding was assigned to the basic region of the bHLH-ZIP domain. Binding was abolished by substitution of 3 amino acids that were previously implicated in DNA binding by Max, another bHLH-ZIP protein. The membrane attachment domain was localized to two hydrophobic regions at residues 477-497 and 536-556. Truncation of SREBP-1 prior to these regions gave rise to an NH2-terminal fragment that was soluble and entered the nucleus. This fragment was more than 30-fold more active than full-length SREBP-1 in stimulating transcription of an SRE-1 containing reporter gene in transfected cells. Deletion of the hydrophobic sequences (delta 476-556) yielded a protein that appeared cytosolic by immunofluorescence microscopy but failed to enter the nucleus readily, apparently because of inhibition by sequences in the remaining COOH terminal domain. This study provides a picture of the domain structure of SREBP-1 and further elucidates the mechanism by which it adjusts gene transcription to maintain cholesterol homeostasis in animal cells. PMID- 8006037 TI - The myogenin gene is activated during myocyte differentiation by pre-existing, not newly synthesized transcription factor MEF-2. AB - The myogenin gene, a member of the gene family encoding muscle-specific basic helix-loop-helix transcription factors, is activated in myoblasts at the onset of differentiation and can be induced in fibroblasts by forced expression of MyoD or its relatives. Here, we report that a small proximal promoter region of the Myf-4 gene, the human myogenin homolog, suffices to direct muscle-specific expression and up-regulation by MyoD. The minimal promoter contains an E-box and a MEF-2 consensus element. Paradoxically, we find that the MEF-2 binding site but not the E-box is necessary for cell type-specific expression and activation by MyoD in tissue culture cells. This suggests an activating mechanism which is independent of direct protein interactions at the E-box. MEF-2 binding complexes were detected in myoblasts and myotubes, as well as in fibroblasts with no strict correlation to myogenin expression. Moreover, transcription of myogenin could be induced in the presence of potent inhibitors of protein synthesis. From these results we conclude that myogenin expression is not mediated primarily through de novo synthesis of MEF-2 but rather involves a post-translational mode of activation. PMID- 8006038 TI - Molecular cloning and characterization of a ras-related gene of ran/tc4/spi1 subfamily in Giardia lamblia. AB - The significance of Ras-like proteins in the protozoa is relatively unexplored. In this report, a gene encoding a Ras-like nuclear (Ran) protein was identified in Giardia lamblia by a polymerase chain reaction-based cloning strategy. The sequence analyses suggest that the gene was intronless, and had short 5' untranslated leader sequences in the corresponding mRNA up to -2, -4, or -29 bases upstream of the first initiation codon. The full-length cDNA sequence predicted a protein comprising 226 amino acids, in which the highly conserved functional motifs of the Ras superfamily were all preserved. This protein showed 52% identity to human TC4 and 50% identity to yeast Spi1 proteins, suggesting that it is closely related to the Ran proteins, and it was therefore designated gRan. gRan produced from recombinant Escherichia coli exhibited GTP binding activity by an overlay assay. In good agreement with the predicted size of gRan, a 27-kDa protein was identified in a lysate of G. lamblia by Western blotting using antiserum raised against recombinant gRan. The protein was further localized in both nuclei of G. lamblia by immunofluorescence staining. Recombinant gRan exhibited low affinity for GTP with a Kd value of 16.8 microM. The affinity was enhanced to a Kd value of 2.2 microM in the presence of 10 mM Mg2+. The intrinsic GTPase activity of gRan was observed only in the presence of 10 mM Mg2+ and had an estimated Km of 5.6 microM and a Kcat of 0.33/h. These observations demonstrate the presence of Ras-like proteins in the most primitive eukaryotic cells, G. lamblia, and infer that the Ran protein may play a functional role in the nuclei of this organism. PMID- 8006039 TI - Characterization of a cDNA encoding the 43-kDa membrane-associated inositol polyphosphate 5-phosphatase. AB - Agonist stimulation of cells results in phosphatidylinositol turnover and the generation of inositol 1,4,5-trisphosphate (Ins(1,4,5)P3), which mobilizes intracellular calcium. The inositol-polyphosphate 5-phosphatase (5-phosphatase) enzymes hydrolyze Ins(1,4,5)P3 in a signal-terminating reaction. We have isolated a 2.7-kilobase (kb) composite cDNA, encoding the 43-kDa membrane-associated 5 phosphatase, by screening a human placental lambda gt11 library, using degenerate oligonucleotides. The 2.7-kb cDNA contains a 1.1-kb open reading frame, comprising 363 amino acids, which encodes a protein of a predicted molecular mass of 42 kDa. Amino acid sequence analysis demonstrates a number of potential sites for phosphorylation by protein kinase C and a CAAX motif in the COOH terminus, which may mediate membrane localization. The recombinant enzyme was expressed in COS-7 cells, resulting in a 50-fold increase in enzyme activity in the detergent soluble membrane fraction of the cell (nanomole of Ins(1,4,5)P3 hydrolyzed per min/mg), but only a 2.5-fold increase in 5-phosphatase activity in the total cell homogenate. Sequence analysis demonstrated a 73-amino acid domain in the COOH terminus of the 43-kDa membrane-associated 5-phosphatase, which had 30% sequence identity and 67% similarity to a region in the 75-kDa 5-phosphatase and 34% identity and 70% similarity to a sequence in the protein that is encoded by the gene, defective in Lowe's oculocerebrorenal syndrome. As shown by RNA analysis the 43-kDa membrane-associated 5-phosphatase appears to be predominantly expressed in heart, brain, and skeletal muscle. PMID- 8006040 TI - Molecular structure of pulmonary surfactant protein D (SP-D). AB - Previous studies have shown that pulmonary surfactant protein D (SP-D) is composed of a 43-kDa polypeptide with a short NH2-terminal domain, a collagen sequence, and a COOH-terminal C-type lectin domain. In the present studies, ultrastructural and biochemical techniques were used to examine the quaternary structure of native rat SP-D (rSP-D). Electron microscopy of freeze-dried preparations demonstrated a highly homogeneous population of molecules with four identical rod-like arms (46 nm in length), each with an 8-9-nm diameter globular terminal expansion. The arms, which are similar in diameter to the type I collagen helix (approximately 4 nm), emanate from the central "hub" in two pairs that closely parallel each other for their first 10 nm. This structure is consistent with hydrodynamic studies that predict an highly asymmetric and extended molecule (f/f0 = 3.26) with a large Stokes radius (Rs = 18 nm). Pepsin digestion gave glycosylated, trimeric collagenous fragments (43 +/- 4 nm, 17 kDa/chain). Trimeric subunits containing intact triple helical domains were also liberated from SP-D dodecamers by sulfhydryl reduction under non-denaturing conditions. Digestion of rSP-D with bacterial collagenase generated a COOH terminal carbohydrate binding fragment and a smaller peptide (approximately 12 kDa, unreduced) that contains interchain disulfide bonds. Electron microscopy also demonstrated higher orders of multimerization, with as many as 8 molecules associated at the hub. These studies demonstrate that SP-D is assembled as homopolymers of four identical trimeric subunits, that interactions between the amino-terminal domains of the trimers are stabilized by interchain disulfide bonds, and that SP-D molecules can associate to form complex multimolecular assemblies. PMID- 8006041 TI - Identification and biological characterization of an epidermal growth factor related protein: cripto-1. AB - The human and mouse cripto-1 (CR-1) genes can code for proteins related in structure to epidermal growth factor (EGF). A specific 36-kDa immunoreactive protein was detected by Western blot analysis in human cell lines that express CR 1 mRNA but not in cell lines that fail to express this transcript. Immunoprecipitation of GEO colon carcinoma or mouse embryonal carcinoma cells detected 27-29-kDa and 24-kDa proteins, respectively. Cell lysates and conditioned medium that were prepared from several CHO clones and were expressing either a recombinant human or mouse CR-1 cDNA contained immunospecific 27-29-kDa and 24-kDa proteins, respectively. Monensin or tunicamycin treatment resulted in a shift of the 27-29-kDa human CR-1 protein to 24 kDa and 20 kDa, respectively. The 20-kDa protein was also observed after digestion of the 27-29-kDa human CR-1 protein with N-glycosidase F. Using two CR-1 synthetic refolded peptides that correspond to the EGF-like domain of the human CR-1 sequence or conditioned medium obtained from human CR-1 expressing CHO cells, growth stimulatory activity could be detected on non-transformed human mammary epithelial cells and on two human breast cancer cell lines. EGF receptor-blocking antibody did not inhibit the growth stimulatory action of the CR-1 protein. Likewise, the CR-1 refolded peptides or conditioned medium from the human CR-1-expressing CHO cells failed to inhibit the binding of 125I-EGF in an EGF-radioreceptor assay. These data demonstrate that the CR-1 is a glycoprotein that can function as a growth factor through an EGF receptor-independent pathway. PMID- 8006042 TI - Post-translational requirements for functional factor V and factor VIII secretion in mammalian cells. AB - Coagulation factors V and VIII are homologous glycosylated plasma proteins that provide essential functions for hemostasis. Factor V is secreted as a single chain polypeptide, whereas factor VIII is processed intracellularly to yield a metal-ion-associated heterodimer that is stabilized through interaction with von Willebrand factor. In transfected mammalian cells, factor V is more efficiently secreted than factor VIII. To provide insight into the different secretion efficiencies, we compared the post-translational processing requirements for factor V and factor VIII expressed in mammalian cells. In contrast to factor VIII, factor V was not detected in association with the immunoglobulin-binding protein (BiP), a chaperonin protein of the endoplasmic reticulum (ER). Depletion of intracellular ATP levels by treatment of cells with low concentrations of carbonyl cyanide 3-chlorophenylhydrazone (CCCP), protonophore that uncouples oxidative phosphorylation, inhibited secretion of factor VIII but had no effect on the secretion of factor V. Inhibition of N-linked oligosaccharide addition by treatment with tunicamycin prevented secretion of both factor V and factor VIII, whereas treatment with an inhibitor of complex oligosaccharide addition, deoxymannojirimycin, did not affect secretion, although the specific activities of both factor V and factor VIII were slightly increased. Thus, complex oligosaccharide addition was not required for secretion or functional activity of either factor V or factor VIII. Depletion of intralumenal calcium with the ionophore A23187 did not affect secretion of either factor V or factor VIII. In the presence of A23187, the secreted factor V was fully functional, whereas the factor VIII heavy and light chains were not associated and the secreted molecule was inactive. In addition, A23187 treatment inhibited addition of serine/threonine (O)-linked oligosaccharides to factor V and factor VIII. The differences between factor V and factor VIII were further evaluated by characterization of a single chain mutant factor VIII. The single chain factor VIII was secreted with an efficiency similar to wild-type factor VIII and also required von Willebrand factor for stabilization. In addition, the activity of single chain factor VIII was also inhibited by A23187 treatment, suggesting a unique metal-ion requirement within the secretory pathway for functional factor VIII folding. The differences identified in BiP association, ATP requirements, and metal-ion dependence for effective functional secretion of these two molecules may underlie mechanisms accounting for their different secretion efficiencies. PMID- 8006043 TI - Mechanism and subcellular localization of secretory IgM polymer assembly. AB - The predominant functions of secreted IgM, complement fixation and transcytosis across epithelial barriers via the poly(Ig) receptor, are properties of IgM polymers; thus, the mechanisms that regulate oligomerization are critical to immune function. We have developed methods to assess the mechanism and subcellular location of IgM polymer formation. Using denaturing agarose/SDS polyacrylamide gel electrophoresis and sucrose gradient fractionation, we demonstrate that IgM polymers are assembled in a stepwise fashion in which primary intermediates, including heavy chain-light chain complexes, are sequentially incorporated. Assembly intermediates include both covalent and non covalent components, suggesting that IgM subunit interactions precede covalent assembly. IgM polymers are assembled from primary intermediates containing immature N-linked oligosaccharides. Polymerization is insensitive to brefeldin A and occurs at temperatures that inhibit protein transport along the secretory pathway. Together, these data demonstrate that IgM polymerization occurs early in the secretory pathway, most likely in the endoplasmic reticulum. These results are consistent with a model in which secretory IgM represents an oligomeric protein that is retained in the endoplasmic reticulum and does not mature along the secretory pathway until complete assembly is achieved. PMID- 8006044 TI - Exon/intron structure of the human alpha 3(IV) gene encompassing the Goodpasture antigen (alpha 3(IV)NC1). Identification of a potentially antigenic region at the triple helix/NC1 domain junction. PMID- 8006045 TI - Interactions of plasminogen and fibrinogen with model silica glass surfaces: adsorption from plasma and enzymatic activity studies. AB - The adsorption of fibrinogen and plasminogen from plasma to silica glass, sulfonated silica glass, and lysine-derivatized silica glass has been investigated. The data indicate that the sulfonated material has a high affinity for both fibrinogen and plasminogen, but that the ratio of plasminogen to fibrinogen is greater on the lysine-derivatized surface. The adsorption data also suggest plasminogen as a possible contributor to the fibrinogen Vroman effect, whereby initially absorbed fibrinogen is displaced from the surface. The plasmin activity of plasminogen adsorbed to the lysine-derivatized silica glass and its sulfonated precursor was assessed by both a chromogenic substrate assay and a radioimmunoassay for the plasmin cleavage product of fibrinogen, the B beta 1-42 peptide. The data indicate that 1) the adsorbed plasminogen is not inherently plasmin-like; 2) the enzymatic activity associated with the bound plasminogen is significantly enhanced on both surfaces in the presence of activator; and 3) in the presence of activator, the plasmin activity per mole of bound plasminogen on the lysinized material is approximately a factor of two greater than on the sulfonated material based on the chromogenic substrate assay, and a factor of four greater based on the B beta 1-42 radioimmunoassay. The lysinized material thus exhibits several properties that are different from its sulfonated precursor. It adsorbs more plasminogen relative to fibrinogen after the Vroman peak, and this adsorbed plasminogen appears to be in a conformation that is more readily activated to plasmin. Once activated, the surface bound plasmin shows enhanced ability to cleave either a low molecular weight chromogenic substrate or a macromolecular substrate.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8006046 TI - Effect of a change in interfacial geometry on the fatigue strength of porous coated Ti-6A1-4V. AB - Porous-coated Ti-6A1-4V has a fatigue strength approximately one-third that of the uncoated alloy. The interfacial geometry between the porous coating and the implant substrate is notchlike, leading to stress concentrations that have been shown to be the main cause for the reduction in fatigue strength. In this study, the effect of interfacial geometry on fatigue strength of porous-coated Ti-6A1-4V is quantified. The interface between porous coating and implant is modeled using linear elastic, plane strain finite element analysis. Integrated with the numerical analysis is an experimental verification of enhanced fatigue behavior. Changes in interfacial geometry are conceived, and their effectiveness in reducing stress concentrations are determined. A doubling of fatigue strength can be achieved for newly conceived geometries over conventional porous coating geometries. PMID- 8006047 TI - In vitro effects of metal ions on cellular metabolism and the correlation between these effects and the uptake of the ions. AB - The effects of Ag+1, Au+3, Cd+2, Cu+2, Ga+3, In+3, Ni+2, Pd+2, and Zn+2 on DNA synthesis, protein synthesis, succinic dehydrogenase activity, and total cellular protein of mammalian fibroblasts were measured for exposures less than 12 h. The rates at which these cellular functions responded to metal ion exposure were compared and related to the uptake rate of the ions into the cells. These rates of response were significantly different: DNA synthesis decreased the fastest, followed by protein synthesis, succinic dehydrogenase activity, and total protein. This order of response was similar for most metal ions. At 4 h, the rate of uptake of the metal ions correlated most closely with depression of succinic dehydrogenase activity, whereas at 8 h, the uptake correlated most closely with depression of protein synthesis. The similar response of cells to all metal ions may imply that these ions act on cells by similar mechanisms. The rates of uptake of Ag+1, Cu+2, and Zn+2 were sufficiently fast that in vivo exposures of tissues to these metals for periods less than 12 h would be capable of disrupting cellular metabolism. PMID- 8006048 TI - Granule secretion markers on fluid-phase platelets in whole blood perfused through capillary tubing. AB - The effect of material composition and shear rate on fluid-phase platelet activation was investigated using a capillary perfusion model. Citrated whole blood was perfused along the lumens of tubes constructed from silicone, PVC, Pellethane, W124 (an experimental polyetherurethane), and glass. Platelet activation was determined by measuring the increase in alpha-granule membrane protein P-selectin (GMP-140, CD62) and the lysosomal granule membrane protein GP 53 (CD63) on fluid-phase platelets by flow cytometry. All tubes caused an increase over the negative control in the number of P-selectin and GP-53 molecules detectable on the surface of these platelets. The activation response of platelets to changes in shear rate was also investigated. It was found that lysosomal release paralleled alpha-granule release in glass, but not in Pellethane, over a range of wall shear rates (100-1,000 s-1). PMID- 8006049 TI - Mathematical modeling of water permeability of surgical fabrics for vascular use. AB - The purpose of this study was to derive new mathemtic formulae that could be used reliably to predict water permeability of surgical fabrics before they are made and tested for water permeability. Such a theoretical prediction of water permeability, Qprd, of surgical fabrics is needed for not only timely characterization but also for assisting in more efficient future design and development of better surgical fabrics. Two mathematic formulae, Qw and Qk, were derived from the Buckingham Pi Theorem, in which relevant fiber and fabric parameters were placed into dimensionless pi groups and computed for 25 commercial and experimental vascular fabrics. Linear regression analysis of the relationship between these pi groups with water permeability on the woven and knitted grafts yielded coefficients for the corresponding pi groups that were required for constructing appropriate mathematic formulae to predict water permeability of vascular fabrics. When proper sources of the experimentally determined water permeability, Qexp, were chosen for comparison, we found that 86% of woven fabrics (6 of 7) and 77% of knitted fabrics (14 of 18) had their Qprd within 10% of their Qexp. This high percentage of close matching (within 10%) between Qprd and Qexp should be considered satisfactory because the experimental error for obtaining Qexp is generally higher than 10%. The difference between Qprd and Qexp ranged from as small as 0.27% to as high as 74.2%, depending on the type of fabrics and source of Qexp.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8006050 TI - Cell growth on poly(vinyl alcohol) hydrogel membranes containing biguanido groups. AB - A cationic, high-water-content hydrogel membrane composed of poly(vinyl alcohol) (PVA) and poly(ally-biguanido-co-allylamine) hydrochloride (PAB) with positively charged biguanido groups that resemble arginine residues was developed. The PAB was prepared by reacting poly(allylamine) hydrochloride (PAA) with guanyl-O methyl isourea. PAB/PVA hydrogel membranes were prepared by repeated freezing and thawing. For comparison, hydrogel membranes composed of PAA and PVA were also prepared. The interaction between these hydrogel membranes and mouse fibroblast (L929) was studied by a cell culture method. The PAB hydrogel blend had a relatively low percentage of initial cell attachment. The cell growth on the PAB hydrogel membranes showed a maximum at 5 mol % PAB content that was as high as commercially available plastic films. However, cells on hydrogel membranes with 50 mol % PAB content and 0 mol % PAB content (only PVA) did not seem to grow; neither did the 5/95 PAA/PVA membranes. Water contact angles of hydrogel membranes did not vary with the PAB content. Morphology of the cell attachment was observed by SEM. On the PAB blend hydrogel surfaces, cells were not spindle shaped and monolayers, but rather cells aggregated in spherical clusters. PMID- 8006051 TI - Biocompatibility of potential wound management products: fungal mycelia as a source of chitin/chitosan and their effect on the proliferation of human F1000 fibroblasts in culture. AB - Aspergillus oryzae, Mucor mucedo, and Phycomyces blakesleeanus cultures were examined as sources of chitin/chitosan. The nitrogen content of the alkali treated mycelia/sporangiophores of A. oryzae, M. mucedo, and P. blakesleeanus was 2.52, 3.61, and 6.27% w/w, which relates to an estimated chitin content of 37, 52, and 91%, respectively. The effect of these fungal materials on the rate of proliferation of human F1000 fibroblasts in culture was examined. At 0.01% w/v, all three materials exhibited significant (P < .05) proproliferant activity over a period of 13 days. However, at 0.05% w/v, P. blakesleeanus further enhanced cell proliferation, whereas A. oryzae and M. mucedo produced a significant (P < .05) antiproliferant effect. Higher concentrations of P. blakesleeanus (0.1 and 0.5%) caused marked inhibition of F1000 cell proliferation when measured on days 3 and 6. Only the proproliferant effect of these fungal materials appears to correlate to their chitin content. Furthermore, the cytomorphology of the fibroblasts indicated that P. blakesleeanus, and to a lesser extent M. mucedo, possessed cell attractant properties, again correlating with chitin content. If developed for use as wound management materials, the sporangiophores of P. blakesleeanus and the mycelium of M. mucedo could possibly promote the growth of fibroblasts and provide a matrix for their anchorage, thus contributing to the granulation phase of the healing cascade. PMID- 8006052 TI - Internalization of poly(D,L-lactic acid) nanoparticles by isolated human leukocytes and analysis of plasma proteins adsorbed onto the particles. AB - The objective of this work was to investigate the interactions of poly(D,L-lactic acid) nanoparticles prepared by a recently developed salting-out process, with lymphocytes and monocytes isolated from healthy human donors. Nanoparticles were labeled with a hydrophobic fluorescent dye and incubated with lymphocytes and monocytes, and their uptake was followed by flow cytometry in the presence and absence of plasma. Plasma protein adsorption increased nanoparticle uptake by monocytes, whereas a decrease of cellular binding of the nanoparticles to lymphocytes was noted. The cellular uptake for both cell types consisted in a passive adsorption and in an energy-requiring process, because the cells became 2 3 times more fluorescent when the incubation temperature was increased from 4 to 37 degrees C. When nanoparticles were coated with polyethylene glycol 20,000, uptake by monocytes decreased by 43 and 78% in phosphate-buffered saline and plasma, respectively; a similar decrease in nanoparticle uptake was observed for lymphocytes. Two-dimensional gel electrophoresis was performed to identify the plasma opsonins adsorbed onto the nanoparticle surface. Protein mappings for uncoated and polyethylene glycol-coated nanoparticles differed for two spot series. These spots, not yet clearly identified, may represent specific apolipoproteins involved in the metabolism of human lipoproteins, indicating the possible involvement of specific receptors in the uptake of the nanoparticles. PMID- 8006053 TI - Degradation of polyetherurethane by subcutaneous implantation into rats. I. Molecular weight change and surface morphology. AB - Two kinds of polyetherurethane (PEU), U-3 and U-8, were coated in thin layers on an ethylene-vinylalcohol copolymer (EVAL) film 0.1 mm thick. U-3 is a nonsegmented PEU prepared from 4,4'-diisocyanatodiphenylmethane (MDI) and poly(tetramethylene oxide) of Mn = 1,000 (PTMO 1000), and U-8 is a segmented PEU prepared from MDI, PTMO 1000, and 1,4-butanediol. The coating thicknesses were 0.0068 and 0.022 mm for U-3 and U-8, respectively. These coated films were implanted subcutaneously into rats and retrieved after various weeks. The coatings on the retrieved samples were dissolved in tetrahydrofuran (THF), and the average molecular weight (MW) was determined by injecting the THF solution into a gel permeation chromatograph. In the case of U-3, MW increased after 2 weeks, then decreased over the implantation period. After 10 weeks, U-3 almost disappeared from the base film. In the case of U-8, MW reached the maximum at 4 weeks postimplantation then decreased gradually over the implantation period. The rate and degree of MW change were greater in U-3 than in U-8. Here, we argue that, in the early stage, low molecular weight PTMO/MDI oligomers leached out from the PEUs to the inflammatory exudate to increase MW, and in the later stage macrophage attachment/activation had a role in the degradation of PEUs. The surface morphologic changes observed by scanning electron microscopy are also discussed. PMID- 8006054 TI - Adsorption of a novel fluorescent derivative of a poly(ethylene oxide)/poly(butylene oxide) block copolymer on octadecyl glass studied by total internal reflection fluorescence and interferometry. AB - We have used total internal reflection fluorescence (TIRF) to measure the adsorption kinetics of a newly synthesized fluorescent derivative of a triblock copolymer comprising two poly(ethylene oxide) arms connected by a poly(butylene oxide) segment. The composition is (EO)400 (BO)55 (EO)400, in which EO represents ethylene oxide, BO represents butylene oxide, and one or both of the terminal OH groups of the two (EO)400 arms are labeled with tetramethylrhodamine. The poly(butylene oxide) segment binds to hydrophobic octadecyl glass, used as a substratum. The TIRF signal is shown to be derived almost entirely from surface adsorbed polymer. This facilitates calculation of adsorption isotherms from 0.1 0.005% bulk polymer solution by means of diffusion kinetics. Information about the effective thickness of the adsorbed polymer, determined by optical interference microscopy, corresponds with what is known about the conformation of similar molecules at interfaces and indicates monolayer adsorption on the glass. PMID- 8006055 TI - Creep of a poly(etherurethane urea) in an oxidative environment. AB - The creep behavior of a PEUU without added stabilizers was examined in H2O2/CoCl2, an environment that simulates the biodegradation of this polymer. Creep in the control environments, air, water, and H2O2, was logarithmic with time as is characteristic of primary or viscoelastic creep. At short times, creep in H2O2/CoCl2 followed the same time dependency as creep in H2O2; however, at longer times an acceleration in the creep rate was observed. Creep in H2O2/CoCl2 was satisfactorily described by addition of a linear time term to the creep equation with an induction time, ti. The induction time was extended by stress induced crystallization of the soft segments, but was reduced by an increase in H2O2 concentration. Oxidative degradation of the PEUU soft segments was detected by infrared and GPC analysis at times less than ti. This led to the speculation that an initial "precursor" layer was created at the surface by chain cleavage. Microcracking in a subsequent stage was postulated to be responsible for the observed effect on the creep behavior. PMID- 8006056 TI - Tissue digestion for wear debris particle isolation. PMID- 8006057 TI - Identification of serum-inducible genes: different patterns of gene regulation during G0-->S and G1-->S progression. PMID- 8006058 TI - Concentration-dependent effects of cytochalasin D on tight junctions and actin filaments in MDCK epithelial cells. AB - The effects of different concentrations of the actin-disrupting drug cytochalasin D on tight junction permeability and distribution of actin filaments in MDCK epithelial cells were examined. Consistent with previous studies, 2 micrograms/ml cytochalasin D caused a significant decrease in transepithelial resistance, indicative of an increase in tight junction permeability. Surprisingly, increasing concentrations of cytochalasin D caused progressively smaller decreases in transepithelial resistance. The effects of cytochalasin D were reversible. Light microscopic analysis utilizing rhodamine-conjugated phalloidin demonstrated two distinct populations of actin filaments in MDCK cells: an apical peripheral ring of actin, presumably associated with the zonula adherens, and larger actin bundles more basally situated. When treated with 2 micrograms/ml cytochalasin D, both actin populations were severely disrupted and cells became flattened. Actin in the apical ring aggregated along cell boundaries, and these aggregates co-localized with similarly disrupted focal accumulations of the tight junction-associated protein ZO-1. The basal actin filament bundles also reorganized into focal aggregates. Increasing concentrations of cytochalasin D caused gradually less perturbation of the apical actin ring, consistent with the transepithelial resistance observations. However, the basal actin bundles were disrupted at all concentrations of cytochalasin D tested, demonstrating that the two actin populations are differentially sensitive to cytochalasin D and that apical actin filaments are more important in the regulation of tight junction permeability. Finally, treatment of cells with cytochalasin D inhibited the decrease in transepithelial resistance induced by the chelation of extracellular Ca2+.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8006059 TI - Rearrangement of mRNAs for costamere proteins during costamere development in cultured skeletal muscle from chicken. AB - Mature skeletal myofibrils are surrounded by costameres, ribs of metavinculin, vinculin, intermediate filaments, and other proteins that connect the myofibril to the extracellular matrix. Costameres have recently been shown to be the sites at which the forces generated by the myofibril are transduced laterally into the extracellular matrix. We observed costameres developing in cultured skeletal muscles, grown in micromass culture from cells taken from embryonic chicken leg. We detected proteins by immunofluorescence and mRNA by in situ hybridization. Antibody and probe signals were imaged by laser scanning confocal microscopy. Antibody to vimentin protein is first detected in stripes in register with the Z line of the myofibril, at approximately day 12 after fusion; soon thereafter probe to vimentin mRNA is also detected in the same stripes. Optical sections indicate that vimentin mRNA and protein are very close, no more than 0.1 mm apart and possibly in immediate contact. Antibody to vimentin is detected in stripes only in cells that twitch spontaneously. Antibodies and probes to desmin and vinculin protein and mRNA are next detected in stripes of the same periodicity, at approximately day 17 after fusion. Vinculin protein (but not mRNA) is detected at focal contacts much earlier in development. Controls for bleed through of fluorescence, RNase H sensitivity, hybridization without probe, and binding to the myofibril all gave appropriate results. Probes to glyceraldehyde-3-phosphate dehydrogenase, a glycolytic enzyme, stained diffusely and did not associate with the myofibril. These results show that components of the costamere arrive at the structure in a defined sequence, and that mRNA organization is a conspicuous, precise and temporally controlled aspect of costamere development. These results may have wider implications. In these cells, some mRNAs are positioned with submicrometer precision in space and differentially over time. Particular mRNAs differ in the time and place of such positioning. This implies both that cellular structures provide physical cues for such positioning and that mRNA contains information that interacts with such cues in a message-specific manner. If such precision in mRNA location is found in other somatic cells, it could have significant implications for the ways in which cells generate and maintain cellular structures. PMID- 8006060 TI - Cytostellin distributes to nuclear regions enriched with splicing factors. AB - Cytostellin, a approximately 240 kDa phosphoprotein found in all cells examined from human to yeast, is predominantly intranuclear in interphase mammalian cells and undergoes continuous redistribution during the cell cycle. Here, mammalian cytostellin is shown to localize to intranuclear regions enriched with multiple splicing proteins, including spliceosome assembly factor, SC-35. Cytostellin and the splicing proteins also co-localize to discrete foci (called 'dots'), which are distributed throughout the cell during mitosis and part of G1. The cytostellin that is localized to these dots resists extraction by Triton X-100, indicating that it is tightly associated with insoluble cell structures. All immunostainable cytostellin reappears in the nucleus before S-phase. Although cytostellin and the splicing proteins co-localize in interphase and dividing cells, cytostellin is not detected in purified spliceosomes, and it associates with six unidentified proteins, forming a macromolecular complex that is biochemically distinct from the proteins that comprise spliceosomes. This macromolecular complex is detected at constant levels throughout the cell cycle, and the level of cytostellin protein remains constant during the cell cycle. Nevertheless, intranuclear cytostellin immunostaining fluctuates markedly during the cell cycle. The monoclonal antibody (mAb) H5 epitope of cytostellin is 'masked' in serum-starved cells, but 60 minutes after serum stimulation intense cytostellin immunoreactivity appears in the nuclear speckles. This rapid induction of cytostellin immunoreactivity in subnuclear regions enriched with many splicing factors, as well as accumulations of RNA polymerase II (Pol II) transcripts, suggests that cytostellin may have a function related to mRNA biogenesis. PMID- 8006061 TI - Dictyostelium prespore-specific gene Dp87 encodes a sorus matrix protein. AB - In this paper we report on the characteristics of the product of a prespore specific gene (Dp87) of Dictyostelium discoideum. Polyclonal antibody was made against a bacterially synthesized Dp87-encoded protein fragment. Using this antibody, the product was characterized by immunochemical and immunocytological methods. It was shown that the Dp87-encoded protein is a prespore-specific protein with a molecular mass of 83 kDa, which first appears at the standing slug stage and persists in mature fruiting bodies. Western blot studies revealed the presence of an additional 81 kDa protein prior to the appearance of the 83 kDa protein from the tipped aggregate to the standing slug stage, thus indicating the former to be a precursor protein. Immunocytochemical and immunoelectron microscopic studies showed that the protein is bound to ER at the early stages of development when only the 81 kDa protein is present. At the later stages when the 83 kDa protein predominates, however, it becomes localized in prespore-specific vacuoles (PSVs) and is associated with the inner fibrous material of PSVs, but not with the peripheral membranous material. This is in contrast to spore coat proteins, which are localized in PSVs from the beginning of their appearance and associated with both structures of PSVs. In mature fruiting bodies, most Dp87 protein is localized to the interspore space (matrix) of the sori, with some left on the surface of the stalk tube. Disruptants of the Dp87 gene were also produced. Although they contained neither 81 kDa nor 83 kDa protein, they showed no phenotypic defects as compared to the parental strain. PMID- 8006062 TI - Isolation and developmental expression of the amphibian homolog of the fibroblast growth factor receptor 3. AB - Recent observations suggest that fibroblast growth factors (FGFs) and their receptors are involved in the control of embryogenesis. Several FGF receptor genes have been identified so far and their expression is differentially regulated. As part of a continuing effort to analyse the differential expression of FGF receptors and their potential role during amphibian development, we have isolated a Pleurodeles homolog of FGF receptor 3 (FGFR-3), which we designated PFR-3 because of its highest homology to human FGFR-3 (75% overall identity). PFR 3 is a maternally derived mRNA. While a low level of expression persists during the cleavage and gastrula stages, a significant increase in the mRNA was observed at the end of the gastrula stage. RNase protection analysis on dissected tissues showed that PFR-3 mRNA was mainly localized to the ectoderm at the early gastrula stage and then shifted to the embryonic neural tissues, whereas adult brain had decreased levels of PFR-3 mRNA expression. Consistent with the loss of FGF receptors during skeletal muscle terminal differentiation, PFR-3 as well as other FGF receptor mRNAs were undetectable in the adult skeletal muscle. However, highest levels of PFR-3 mRNA expression were found in the testis. In situ hybridization revealed strong expression in the germinal epithelium of the embryonic brain (especially the diencephalon and rhombencephalon) and neural tube, in the lens and the cranial ganglia. The epithelium of the developing gut, like the pharynx and esophagus, also prominently expressed PFR-3 mRNA. Other sites of expression were found in the liver and in the mesenchymal condensation sites of branchial arches.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8006063 TI - Species specificity and organ, cellular and subcellular localization of the 100 kDa Ras GTPase activating protein. AB - A p100-GAP isoform, generated by an alternative splicing mechanism that eliminates the 180 hydrophobic amino acids at the amino terminus of p120-GAP, has been described in human placenta, in addition to the known p120GAP and neurofibromin. This p100-GAP possesses full Ras-GTPase stimulating activity. p120 GAP is ubiquitously localized in the cytosol while the localization of p100-GAP is unknown. Here we have explored the precise localization of p100-GAP and show that p100-GAP is present only in extracts of primate placenta. It is abundant in both human and Maccaca Rhesus placentae, where it is present in far larger amounts than p120-GAP. The p100-GAP is species-specific since it was not detected in the placenta of pig, sheep, mouse or rat. p100-GAP was also found to be organ specific, since it was not detectable in organs other than the placenta. In this connection, we substantiated our previous finding that p100-GAP is mainly localized in the trophoblasts. Both subcellular trophoblast fractionation and immunofluorescence analyses showed that this protein was distributed between the cytosol, plasma membrane and a fraction bound to the nucleus, but not inside it. This highly restrictive specificity of p100-GAP localization in relation to species, organ and cell type, confirms the extreme singularity of this protein, and strongly suggests a particular specific function in the trophoblast. PMID- 8006064 TI - Calponin is localised in both the contractile apparatus and the cytoskeleton of smooth muscle cells. AB - Calponin and caldesmon are two thin filament-binding proteins found in smooth muscle that have both been attributed a role in modulating the interaction of actin and myosin. Using high-resolution dual-label immunocytochemistry we have determined the distribution of calponin relative to the contractile and cytoskeletal compartments of the smooth muscle cell. We show, using chicken gizzard smooth muscle, that calponin occurs in the cytoskeleton, with beta cytoplasmic actin, filamin and desmin, as well as in the contractile apparatus, with myosin and caldesmon. According to the observed labelling intensities, calponin was more concentrated in the cytoskeleton and it was additionally localised in the cytoplasmic dense bodies as well as in the adhesion plaques at the cell surface, which both harbour the beta-cytoplasmic isoform of actin. It is probable that these results explain earlier conflicting reports on the composition of smooth muscle thin filaments and suggest that calponin, together with a Ca(2+)-receptor protein, could just as likely serve a role in the cytoskeleton of smooth muscle as in the contractile apparatus. PMID- 8006065 TI - Actin isoform compartments in chicken gizzard smooth muscle cells. AB - Differentiated smooth muscle cells typically contain a mixture of muscle (alpha and gamma) and cytoplasmic (beta and gamma) actin isoforms. Of the cytoplasmic actins the beta-isoform is the more dominant, making up from 10% to 30% of the total actin complement. Employing an antibody raised against the N-terminal peptide specific to beta-actin, which labels only the beta-isoform on two dimensional gel immunoblots, we have shown that this isoform has a restricted localisation in smooth muscle. Using double-label immunofluorescence and immunoelectron microscopy of ultrathin sections of chicken gizzard, beta-actin was localised in the dense bodies and in longitudinal channels linking consecutive dense bodies that were also occupied by desmin. It was additionally found in the membrane-associated dense plaques, but was excluded from the actomyosin-containing regions of the contractile apparatus. Taken together with earlier results these findings identify a cytoskeletal compartment containing intermediate filaments, cytoplasmic actin and the actin cross-linking protein filamin. Using an antibody specific only for muscle actin, labelling was found generally around the myosin filaments of the contractile apparatus, but was absent from the core of the dense bodies that contained beta-actin. Thus, if dense bodies act as dual-purpose anchorage sites, for the cytoskeletal actin and the contractile actin, the thin filaments of the contractile apparatus must be anchored at the periphery of the dense bodies. A model of the structural organisation of the cell is presented and the possible roles of the cytoskeleton are discussed. PMID- 8006066 TI - The spatial localization of 18 S rRNA genes, in relation to the descent of the cells, in the root cortex of Petunia hybrida. AB - The 3-D localization of transcription inactive 18 S rRNA genes was studied in interphase nuclei of Petunia hybrida root tip cells. To enable a cell type (i.e. cortex)-specific study in which also the orientation and descent of the cells could be taken into account, a method was developed to preserve the spatial organization of the root meristem. The ribosomal genes were detected by fluorescence in situ hybridization using a biotinylated cDNA probe. 3-D images of 81 nuclei, obtained by confocal scanning laser microscopy, were processed with newly developed computer software. 3-D nucleolar and nuclear dimensions, and the localization of the FISH-spots, were recorded interactively. We compared the absolute and relative position of the genes within and between files of cells of the cortex region of several roots, taking into account the genealogical relationship of the cells. Statistical analysis showed that both the relative and absolute positions of the inactive genes were random, also in more closely related cells within a file of cells. A 'relict telophase orientation' of the genes (i.e. the position of the genes in the daughter cells are mirror images of each other) could only be observed in the G0/1 phase of 'true' daughter cells; the orientation was not preserved throughout the next cell cycle. PMID- 8006067 TI - Unusual chromosome structure of fission yeast DNA in mouse cells. AB - Chromosomes from the fission yeast Schizosaccharomyces pombe have been introduced into mouse cells by protoplast fusion. In most cell lines the yeast DNA integrates into a single site within a mouse chromosome and results in striking chromosome morphology at metaphase. Both light and electron microscopy show that the yeast chromosome region is narrower than the flanking mouse DNA. Regions of the yeast insert stain less intensely with propidium iodide than surrounding DNA and bear a morphological resemblance to fragile sites. We investigate the composition of the yeast transgenomes and the modification and chromatin structure of this yeast DNA in mouse cells. We suggest that the underlying basis for the structure we see lies above the level of DNA modification and nucleosome assembly, and may reflect the attachment of the yeast DNA to the rodent cell nucleoskeleton. The yeast integrant replicates late in S phase at a time when G bands of the mouse chromosomes are being replicated, and participates in sister chromatid exchanges at a high frequency. We discuss the implications of these studies to the understanding of how chromatin folding relates to metaphase chromosome morphology and how large stretches of foreign DNA behave when introduced into mammalian cells. PMID- 8006068 TI - Expression and cellular localization of glucose transporters (GLUT1, GLUT3, GLUT4) during differentiation of myogenic cells isolated from rat foetuses. AB - Skeletal muscle regeneration is mediated by the proliferation of myoblasts from stem cells located beneath the basal lamina of myofibres, the muscle satellite cells. They are functionally indistinguishable from embryonic myoblasts. The myogenic process includes the fusion of myoblasts into multinucleated myotubes, the biosynthesis of proteins specific for skeletal muscle and proteins that regulates glucose metabolism, the glucose transporters. We find that three isoforms of glucose transporter are expressed during foetal myoblast differentiation: GLUT1, GLUT3 and GLUT4; their relative expression being dependent upon the stage of differentiation of the cells. GLUT1 mRNA and protein were abundant only in myoblasts from 19-day-old rat foetuses or from adult muscles. GLUT3 mRNA and protein, detectable in both cell types, increased markedly during cell fusion, but decreased in contracting myotubes. GLUT4 mRNA and protein were not expressed in myoblasts. They appeared only in spontaneously contracting myotubes cultured on an extracellular matrix. Insulin or IGF-I had no effect on the expression of the three glucose transporter isoforms, even in the absence of glucose. The rate of glucose transport, assessed using 2 [3H]deoxyglucose, was 2-fold higher in myotubes than in myoblasts. Glucose deprivation increased the basal rate of glucose transport by 2-fold in myoblasts, and 4-fold in myotubes. The cellular localization of the glucose transporters was directly examined by immunofluorescence staining. GLUT1 was located on the plasma membrane of myoblasts and myotubes. GLUT3 was located intracellularly in myoblasts and appeared also on the plasma membrane in myotubes. Insulin or IGF-I were unable to target GLUT3 to the plasma membrane. GLUT4, the insulin regulatable glucose transporter isoform, appeared only in contracting myotubes in small intracellular vesicles. It was translocated to the plasma membrane after a short exposure to insulin, as it is in skeletal muscle in vivo. These results show that there is a switch in glucose transporter isoform expression during myogenic differentiation, dependent upon the energy required by the different stages of the process. GLUT3 seemed to play a role during cell fusion, and could be a marker for the muscle's ability to regenerate. PMID- 8006069 TI - Targeting of chimeric G alpha i proteins to specific membrane domains. AB - Heterotrimeric guanine nucleotide-regulatory (G) proteins are associated with a variety of intracellular membranes and specific plasma membrane domains. In polarized epithelial LLC-PK1 cells we have shown previously that endogenous G alpha i-2 is localized on the basolateral plasma membrane, whereas G alpha i-3 is localized on Golgi membranes. The targeting of these highly homologous G alpha i proteins to distinct membrane domains was studied by the transfection and expression of chimeric G alpha i proteins in LLC-PK1 cells. Chimeric cDNAs were constructed from the cDNAs for G alpha i-3 and G alpha i-2 and introduced into a pMXX eukaryotic expression vector containing a mouse metallothionein-I promoter. Stably transfected cell lines were produced that expressed either G alpha i-2/3 or G alpha i-3/2 chimeric proteins. Chimeric and endogenous G alpha i proteins were detected in cells using specific carboxy-terminal peptide antibodies. Immunofluorescence staining was used to localize endogenous and chimeric G alpha i proteins in LLC-PK1 cells. The staining of chimeric proteins was detected as an increased intensity of staining on membranes containing endogenous G alpha i proteins. Using confocal microscopy and image analysis we localized G alpha i-2 to a specific sub-domain of the lateral membrane of polarized cells, the chimeric G alpha i-3/2 protein was then shown to colocalize with endogenous G alpha i-2 in the same lateral plasma membrane domain. The chimeric G alpha i-2/3 protein colocalized with endogenous G alpha i-3 on Golgi membranes in LLC-PK1 cells. These results show that chimeric G alpha i proteins were targeted to the same membrane domains as endogenous G alpha i proteins and the specificity of their membrane targeting was conferred by the carboxy-terminal end of the proteins. These data provide the first evidence for specific targeting information contained in the carboxy termini of G alpha i proteins, which appears to be independent of amino-terminal membrane attachment sites in these proteins. PMID- 8006070 TI - A three-dimensional reconstruction study of the rough ER-Golgi interface in serial thin sections of the pancreatic acinar cell of the rat. AB - Distinctive views of the tubulo-vesicular elements interposed between the endoplasmic reticulum (ER) and the Golgi apparatus were obtained in thin sections. The tubules that protrude from the transitional rough ER (tRER) are of dissimilar length. The numbers of tubules and of the nearby omega- and pear shaped profiles decrease after fasting and are partially restored by refeeding. This formation is designated herein as the budding chamber of the tRER. Close to the budding chamber, clusters of 56 nm diameter vesicles are consistently observed. In some of the cells, convoluted tubules appear enmeshed with the presumptive transport vesicles of 56 nm diameter and with irregular, vesicular formations. Apparently structureless, electron-lucent ellipsoidal areas are found adjacent to these membranous elements. Serial and semi-serial sections show that the budding chamber, the sinuous tubules, the irregular vesicles, the structureless regions and the 56 nm vesicles fill tunnel-like spaces limited by the outermost Golgi cisterna (OGC) on one side and by the tRER on the other. Curved tubules appear to link the lumen of the OGC with that of smooth membranous occupants of these tunnel-like spaces. A presumptive luminal connection between these membranous occupants and the tubules of the budding chamber can also be seen. The predominant configuration of the OGC is that of a perforated, flat saccule. However, OGC regions exhibiting progressively lower densities of fenestrae, including smooth surfaced sectors eventually accumulating an intraluminal content are seen. Two such dilated, saccular portions of the OGC were analyzed through reconstruction of serial sections. Bundles of microtubules run closely apposed to the cis side of the OGC. PMID- 8006071 TI - A hypothesis on the traffic of MG160, a medial Golgi sialoglycoprotein, from the trans-Golgi network to the Golgi cisternae. AB - We have reported that MG160, an intrinsic membrane sialoglycoprotein of the Golgi apparatus (GA), resides in the medial cisternae of the organelle (Gonatas et al. (1989) J. Biol. Chem. 264, 646-653). In order to resolve the question whether MG160 acquires sialic acid residues in the trans cisternae or trans-Golgi network (TGN) prior to its retrograde transport, we have examined the effects of brefeldin A (BFA) on the post-translational processing of MG160, and the distribution of internalized wheat germ agglutinin covalently linked with HRP (WGA-HRP), which labels the TGN (Gonatas et al. (1977) J. Cell Biol. 73, 1-13). In BFA-treated PC12 cells, MG160 acquires resistance to endo H, but fails to be sialylated. This effect occurs in parallel with the redistribution of MG160 into an ER compartment dispersed throughout the cytoplasm including the nuclear envelope, and the collapse of the WGA-HRP-labelled TGN into vesicles and tubules surrounding the centriole. These results suggest that MG160 is not sialylated in BFA-treated cells because it is sequestered from the sialyltransferase enzyme(s), presumably located in the TGN, and provide evidence supporting the hypothesis for a retrograde transport pathway that recycles resident GA proteins, including MG160, between the Golgi cisternae and the TGN. To examine further the above hypothesis we studied cells treated with BFA and then allowed to recover from the effect of the drug for various lengths of time. After 15 minutes of recovery, cisternae of the Golgi apparatus, typically found in the pericentriolar region, are labeled by both MG160 and WGA-HRP.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8006072 TI - Adhesive properties and integrin expression profiles of two colonic cancer populations differing by their spreading on laminin. AB - The mostly undifferentiated parental HT29 (HT29p) human colonic adenocarcinoma cell line and a differentiated subpopulation selected by the anti-cancer drug 5 fluorouracil (HT29-Fu) (Lesuffleur et al. (1991) Int. J. Cancer 49, 721-730) display strikingly different behavior when grown on laminin coatings: the former grows as aggregates while the latter grows as monolayers. In an attempt to explain this difference, we performed a comparative study of cell adhesion properties and of expression, involvement and localization of the alpha 6, beta 1 and beta 4 subunits constituting the integrin family among the two cell populations. HT29p and HT29-Fu cells exhibited a similar adhesion pattern to laminin and laminin fragments E8 and P1. In both cell lines, cell adhesion could be blocked at about 90% with anti-alpha 6 subunit antibodies and around 30-50% with anti-beta 1 antibodies; no inhibition of the cell adhesion was obvious when using anti-beta 4 antibodies. Immunoprecipitations of iodinated membrane solubilized proteins and immunoblotting experiments showed that all alpha 6 chains expressed in both HT29p and HT29-Fu cell populations exist as alpha 6 beta 4 integrins; beta 1 subunits are associated with alpha 2 and alpha 3 chains. When HT29p or HT29-Fu cells were injected subcutaneously in nude mice, a similar expression pattern of alpha 6, beta 4 and beta 1 integrin subunits was noticeable in the resulting tumors: alpha 6 and beta 4 subunits were localized at the basal surface of the tumor cells facing the stromal elements, and to a lesser extent at the cell-cell contacts within the tumor-cell clumps; beta 1 subunits were mainly found within the cytoplasm of the tumor cells. Despite these overall similarities among the two cell lines, the following changes could account for their different behavior on laminin: less proteolytic processing of the beta 4 integrin subunit occurred in HT29-Fu cells yielding peptidic fragments of 175 kDa, which are absent from the parental cells; the immunostaining pattern of the various subunits demonstrated a segregation of alpha 6, beta 4 and beta 1 integrin subunits on the basal side of the HT29-Fu cells when cultured on laminin to the detriment of their lateral location, a phenomenon that was not obvious in the parental cells. Altogether, these results suggest that the distinct behavior of the undifferentiated versus differentiated HT29 cell populations on laminin is not related to altered adhesion properties of the cells but rather to a deficient stabilization of the adhesion leading to cell spreading.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8006073 TI - Cell attachment to extracellular matrix substrates is inhibited upon downregulation of expression of calreticulin, an intracellular integrin alpha subunit-binding protein. AB - We have demonstrated recently that calreticulin, an intracellular calcium-binding protein, can interact with the alpha-subunits of integrin receptors via the highly conserved KXGFFKR amino acid sequence present in the cytoplasmic domains of all integrin alpha-subunits (Rojiani et al. (1991) Biochemistry 30, 9859 9866). Here we demonstrate that calreticulin can be co-localized by immunofluorescence as well as co-purified with integrins, that recombinant calreticulin can also interact with integrins, and that the interaction occurs predominantly via the N-domain of calreticulin, to a much lesser extent with the C-domain, but not at all with the proline-rich P-domain. To demonstrate a physiological role for the interaction of calreticulin with integrins, calreticulin expression was downregulated by treating cells with antisense oligonucleotides designed to inhibit the initiation of translation of calreticulin. Antisense oligonucleotides, but not sense or non-sense oligonucleotides, inhibited attachment and spreading of cells cultured in the presence of fetal bovine serum, and also of cells plated on individual extracellular matrix substrates in the absence of serum. The antisense oligonucleotide inhibited cell proliferation of anchorage-dependent cells slightly, but there was no effect on cell viability. The effect on cell attachment was similar to that achieved by treating cells with an antisense oligonucleotide designed to inhibit translation of the integrin alpha 3 subunit, which resulted in the inhibition of cell attachment to alpha 3 beta 1-specific substrates. The effect of the antisense calreticulin oligonucleotide on cell attachment was demonstrated to be integrin-mediated since antisense calreticulin treatment of Jurkat cells abrogated the stimulation of collagen cell attachment achieved by attachment-stimulating signalling anti-alpha 2 (JBS2) and anti-beta 1 (21C8) antibodies. The oligonucleotides did not affect the rate of cell proliferation of these cells. These results demonstrate a fundamental role of calreticulin in cell-extracellular matrix interactions. PMID- 8006075 TI - Study of the higher eukaryotic gene function CDK2 using fission yeast. AB - In the fission yeast Schizosaccharomyces pombe, cdc2 function is required both in G1 to enter the cell cycle and in G2 to initiate mitosis. In higher eukaryotes, these functions appeared to be shared between several cdc2-like genes including CDK2. Temperature-sensitive mutations in S. pombe cdc2 that arrest the cell cycle in both G1 and G2 phases are not complemented by CDK2. We have used S. pombe to investigate what functions CDK2 can perform. We found that overexpression of the human homologue (HsCDK2) caused cell cycle arrest in G2/M showing that HsCDK2 interfered with mitotic events. Xenopus CDK2 (XlCDK2) overexpression did not cause cell cycle arrest and could rescue the G1 block but not the G2 block of a cdc2-M26 ts strain. A mutant XlCDK2-R33, which is inactive as a kinase, failed to rescue the G1 block, suggesting that the protein kinase activity of CDK2 is required to enter the cell cycle in these circumstances. We designed screens to select mutants that would require XlCDK2 expression for viability, hoping to isolate new gene functions interacting with, or that could be replaced by, XlCDK2 in G1, or new cdc2 mutants altered solely in their G1 role. From these screens several cell cycle mutants were selected that were XlCDK2-dependent. These were all cdc2 mutants altered only in their G2/M function. Therefore XlCDK2 can influence both the G1/S and G2/M transition points of cdc2 in S. pombe. PMID- 8006074 TI - Analysis of the Schizosaccharomyces pombe cyclin puc1: evidence for a role in cell cycle exit. AB - The puc1+ gene, encoding a G1-type cyclin from the fission yeast Schizosaccharomyces pombe, was originally isolated by complementation in the budding yeast Saccharomyces cerevisiae. Here, we report the molecular characterization of this gene and analyse its role in S. pombe. We fail to identify any function of this cyclin at the mitotic G1/S transition in S. pombe, but demonstrate that it does function in exit from the mitotic cycle. Expression of the puc1+ gene is increased during nitrogen starvation, and puc1 affects the timing of sexual development in response to starvation. Overexpression of the puc1 protein blocks sexual development, and rescues pat1ts cells, which would otherwise undergo a lethal meiosis. We conclude that puc1 contributes to negative regulation of the timing of sexual development in fission yeast, and functions at the transition between cycling and non-cycling cells. PMID- 8006076 TI - Association of cytoplasmic dynein with manchette microtubules and spermatid nuclear envelope during spermiogenesis in rats. AB - During spermiogenesis, the shape of the spermatid nucleus, which is spherical, changes and it becomes the sperm head. A microtubular structure called a manchette is thought to be involved in this morphogenetic process. In this report, we demonstrate the localization of cytoplasmic dynein and manchette development by a double immunofluorescence technique using anti-bovine brain MAP 1C and anti-tubulin. Before step 6 of the Leblond and Clermont staging, the microtubules showed a fine reticular network, and the dynein staining was homogeneous. In step 6, the microtubular network was concentrated around the nucleus. The manchette developed in step 7 spermatids, and was fully formed, with a skirt-like appearance, covering the nuclear surface in step 8. Dynein fluorescence was associated with the microtubular manchette in steps 7-10. During these steps, the nucleus was protruded from the cytoplasm. In steps 11-13, the most active stages in nuclear shaping, the dynein was densely localized at the nuclear surface covered by the manchette. As the nucleus acquired a shape similar to the mature spermatozoon at step 14, the dynein fluorescence was localized only at the concave side of the nuclear caudal edge. The manchette became narrower and elongated. In step 15, the manchette extended into the elongated cytoplasm, diminishing during steps 16-18. The localization of the dynein was limited to the ventral aspect of the caudal head in these steps. There was little dynein fluorescence in mature spermatozoa. Immunoelectron microscopy showed positive reactions in the nuclear envelope and the inner region of the microtubular manchette. These observations suggest that cytoplasmic dynein, possibly bound to the nuclear envelope, and manchette microtubules are involved in the protrusion of the spermatid nucleus from the cytoplasm. PMID- 8006077 TI - Sequence analysis of the Chlamydomonas alpha and beta dynein heavy chain genes. AB - We have sequenced genomic clones spanning the complete coding region of one heavy chain (beta) and the catalytic domain of a second (alpha) of the Chlamydomonas reinhardtii flagellar outer arm dynein ATPase. The beta heavy chain gene (ODA-4 locus) spans 20 kb, is divided into at least 30 exons, and encodes a predicted 520 kDa protein. Comparison with sea urchin beta dynein sequences reveals homology that extends throughout both proteins. Over the most conserved central catalytic region, the Chlamydomonas alpha and beta chains are equally divergent from the sea urchin beta chain (64% and 65% similarity, respectively), whereas the Chlamydomonas gamma chain is more divergent from urchin beta (54% similarity). The four glycine-rich loops identified as potential nucleotide binding sites in other dynein heavy chains are also present in Chlamydomonas alpha and beta dyneins. Two of these four nucleotide-binding motifs are highly conserved among flagellar dyneins, but only the motif previously identified as the catalytic site in sea urchin dynein is highly conserved between flagellar and cytoplasmic dynein heavy chains. Predictions of secondary structure suggest that all dynein heavy chains possess three large domains, with the four nucleotide binding consensus sequences located in a central 185 kDa domain that is bounded on both sides by regions that form multiple, short alpha-helical coiled-coils. PMID- 8006079 TI - Identification of a novel microtubule-binding domain in microtubule-associated protein 1A (MAP1A). AB - Several microtubule-associated proteins (MAPs) have been shown to bind to microtubules via short sequences with repeated amino acids motifs. A microtubule binding domain has hitherto not been defined for the adult brain microtubule associated protein 1A (MAP1A). We have searched for a microtubule-binding domain by expressing different protein regions of MAP1A in cultured cell lines using cDNA constructs. One construct included an area with homology to the microtubule binding domain of MAP1B (Noble et al. (1989) J. Cell Biol. 109, 437-448), but this did not bind to microtubules in transfected cells. Further investigation of other areas of MAP1A revealed a protein domain, capable of autonomously binding to microtubules, which bears no homology to any previously described microtubule binding sequence. This MAP1A domain is rich in charged amino acids, as are other mammalian microtubule-binding domains, but unlike them has no identifiable sequence repeats. Whereas all previously described mammalian microtubule-binding domains are basic, this novel microtubule-binding domain of MAP1A is acidic. The expression of this polypeptide in cultured cell lines led to a rearrangement of the microtubules in a pattern distinct from that produced by MAP2 or tau, and increased their resistance to treatment with the microtubule depolymerising agent nocodazole. When the MAP1A microtubule-binding domain was co-expressed in cultured cell lines together with MAP2c, the MAP1A microtubule-binding domain was able to bind to the MAP2c-induced microtubule bundles. These results suggest that different microtubule-binding sequences have a common ability to stabilise microtubules but differ in their influence on microtubule arrangement in the cell. This may be significant in neurons, where microtubule-associated proteins with different microtubule-binding sequences are expressed in different cell compartments and at different times during development. PMID- 8006078 TI - Induction of stable microtubules in 3T3 fibroblasts by TGF-beta and serum. AB - Previous studies have shown that fibroblasts induced to migrate into an in vitro wound rapidly generate an array of stable, post-translationally detyrosinated microtubules (Glu MTs) oriented toward the direction of migration. To understand how cells generate a stable array of MTs at a specific location, we have analyzed the contribution of media components to the formation of oriented Glu MTs in wounded monolayers of 3T3 fibroblasts. When confluent monolayers were placed in serum-free medium (SFM) for 2 days before wounding, the cells contained virtually no Glu MTs or nocodazole-resistant MTs and were incapable of generating Glu MTs in response to wounding. Such SFM-treated monolayers were capable of generating oriented Glu MTs within 1 hour of wounding, if calf serum (CS) was added back to the medium. The Glu MTs in the CS refed cells were oriented toward the wound in cells at the wound edge, and were juxtanuclear in cells within the monolayer, demonstrating that CS restored the Glu MT array characteristic of each cell type. To determine the nature of the 'Glu MT-inducing' factor in CS, we subjected CS to different treatments and found that the CS factor was nondialyzable, resistant to heat, mild acid and trypsin, but inactivated by treatment with dithiothreitol. The factor was not absorbed by charcoal and was present in lipoprotein-deficient serum. These properties are consistent with the properties of a number of polypeptide growth factors, so we screened purified growth factors for their ability to induce Glu MTs in wounded SFM-treated monolayers. Of all the growth factors tested, only TGF-beta 1 and TGF-beta 2 induced a significant level (> or = 70% of the CS response) of oriented Glu MTs. The SFM-treated cells were exquisitely sensitive to TGF-beta 1, with significant induction of Glu MTs observed at 0.01 ng/ml TGF-beta 1. Induction of Glu MTs observed by immunofluorescence after CS or TGF-beta treatments were paralleled by increases in Glu tubulin detected on western blots. The Glu MTs formed after either CS or TGF-beta 1 treatment showed enhanced resistance to nocodazole, confirming that both treatments increased the level of stable MTs in cells. The TGF-beta 1 induction of stable MTs was slower than that of CS (2-4 hours onset versus 1 hour onset), but by 24 hours the level of MT stabilization in TGF-beta 1 was even greater than that in CS.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8006080 TI - The distribution of cytoplasmic bacteria in the early Drosophila embryo is mediated by astral microtubules. AB - Maternally inherited cytoplasmic bacteria have occasionally been observed in embryos and adults of different strains of several Drosophila species. While there is a considerable body of data on the relationship between bacteria and embryo viability, little is known about the behavior of these bacteria during the early development of Drosophila. In eggs laid by infected Drosophila melanogaster females we showed that cytoplasmic bacteria were initially concentrated in a thin cortical layer and scattered in the yolk region. During the following syncytial blastoderm mitoses the bacteria mainly accumulated towards the poles of the mitotic spindles, suggesting that astral microtubules play a role in localizing bacteria. This is supported by the observation that treatment of the infected embryos with the microtubule-disrupting drug colchicine led to the partial dissociation of the bacteria from the spindle poles, whereas cytochalasin treatment left almost all the bacterial clusters intact. Moreover, bacteria were not found near the polar bodies and yolk nuclei, which were without astral microtubules. In mitosis-defective embryos, with centrosomes dissociated from the nuclei, the bacteria were concentrated in association with the isolated astral microtubules, and in cold-treated embryos, in which microtubules regrew from isolated centrosomes after recovering, the bacteria clustered around the newly formed asters. These observations, also supported by electron microscope analysis, indicate a close relationship between cytoplasmic bacteria and astral microtubules, and suggest that the latter were able to build discrete cytoplasmic domains ensuring the proper distribution of cytoplasmic components during the blastoderm mitoses, despite the lack of cell membranes. PMID- 8006081 TI - Cytoskeletal involvement in the modulation of cell-cell junctions by the protein kinase inhibitor H-7. AB - The protein kinase inhibitor H-7 has been shown to block junction dissociation induced by low extracellular calcium in Madin Darby canine kidney epithelial cells (S. Citi, J. Cell Biol. (1992) 117, 169-178). To understand the basis of this effect, we have examined how H-7 affects the organization of junctions and the actin cytoskeleton in different types of epithelial cells in culture. Immunofluorescence microscopy showed that H-7 confers Ca2+ independence on cultured epithelial lens cells, which lack tight junctions and desmosomes but have microfilament-associated adherens junctions. In these cells, H-7 did not protect N-cadherin from trypsin digestion at low extracellular calcium, suggesting that H-7 does not stabilize the 'active' cadherin conformation. In cultured Madin Darby canine kidney cells, H-7 partially prevented the fall in transepithelial resistance induced by cytochalasin D, either alone or in conjunction with calcium chelators. Double-immunofluorescence microscopy showed that H-7 inhibits both the fragmentation of labeling for the tight junction protein cingulin and the condensation of actin into cytoplasmic foci induced by cytochalasin D. Taken together, these observations indicate that H-7 inhibits junction dissociation by affecting the contractility of the adherens junction associated microfilaments following treatment with calcium chelators or cytochalasin D. PMID- 8006082 TI - Exogenous histone H1 injection into mitotic cells disrupts synchronous progression of mitotic events by delaying chromosome decondensation. AB - At the end of open mitosis, chromosome decondensation, nuclear envelope re formation and reassembly of interphase microtubules following mitotic spindle dissociation occur coordinately. To determine whether these events progress only synchronously in vivo, we delayed chromosome decondensation by injecting of exogenous proteins into the mitotic rat kangaroo kidney epithelium (PtK2) cells. When histone H1 purified from calf thymus was injected at prometaphase, chromosome condensation was prolonged for several hours, and sister chromatid separation and cytokinesis did not occur. However, interphase microtubules reassembled and lamin B-positive structures re-formed around the condensed chromosomes. Exactly the same results were obtained on injection of bacterially expressed H1. Kinetic experiments showed that there were two types of lamin B positive structures. One type (type A) was stained uniformly with anti-lamin B antibodies. The other (type B) showed peripheral lamin B staining; that is, the normal interphase staining pattern, and was found to be competent for nuclear protein transport. As the chromosomes decondensed, the amount of type A decreased and that of type B increased. However, even cells containing highly condensed chromosomes had both type A and type B. From these results, we conclude that the re-formation of microtubules and reassembly of a nuclear transport-competent envelope do not depend on chromosome decondensation. PMID- 8006083 TI - A molecular analysis of the origin of the Crepis capillaris B chromosome. AB - The origin of the B chromosome of Crepis capillaris has been studied by using in situ hybridization with different DNA probes. Genomic in situ hybridization (GISH) with DNA from plants with and without Bs as probes indicates that the B chromosome has many DNA sequences in common with A chromosomes, showing no region rich in B-specific sequences. Six additional DNA probes were used to test the possible origin of this B from the standard NOR chromosome (chromosome 3). In the short arm of the NOR chromosome, we detected not only 18 S + 25 S rDNA, but also 5 S rDNA and a specific repetitive sequence from the NOR chromosome (pCcH32); in the heterochromatic bands of the long arm, we found two different repetitive sequences (pCcE9 and pCcD29). In the B chromosome, however, only the 18 S + 25 S rDNA and the telomeric sequences from Arabidopsis thaliana were observed. Our in situ hybridization data with telomeric repeats indicate that the two telomeres of the B are larger than those of the A chromosomes, confirming the isochromosomal nature of this B. Hybridizations of 18 S + 25 S rDNA and telomeric repeats to blots of DNA from plants with and without Bs reveal a high homology between A and B 18 S + 25 S rDNA genes, but some sequence dissimilarities between A and B telomeres. Taken as a whole, these data indicate that the entire B of C. capillaris, although possibly having originated from the standard genome, did not derive directly from the NOR chromosome. PMID- 8006084 TI - Cloning of Drosophila beta-adaptin and its localization on expression in mammalian cells. AB - A Drosophila cDNA (BAD1) encoding a structural and assembly-competent homologue of the mammalian coated pit beta-adaptins (beta and beta') has been cloned and sequenced. In its amino-terminal region (residues 1-575), the BAD1 sequence appears intermediate between that of the mammalian beta-adaptin and a predicted sequence, from cDNA 105a, which appears to code for a version of beta'-adaptin. To test its functional characteristics, a 'myc'-tagged version of BAD1 was expressed in Cos cells. The BAD1 protein was detected most clearly in plasma membrane coated pits, where it colocalized with alpha-adaptin, although other coated pits were noted which apparently did not contain alpha-adaptin. However, these are probably gamma-adaptin containing pits, as BAD1 was also found colocalized with gamma-adaptin in Golgi coated pits in which, typically, alpha adaptin is absent. Immunoprecipitation experiments confirmed that the BAD1 protein was present in both types of adaptor complex, unlike beta-adaptin which complexes with alpha-adaptin and beta'-adaptin which partners gamma-adaptin exclusively. In spite of this, BAD1 expression does not appear to mix alpha adaptin and gamma-adaptin distribution amongst all the coated pits: thus the location of these adaptor complexes in mammalian cells does not depend on the differences between beta subunits but rather on membrane-specific interactions of other adaptor polypeptides. The differential interaction of beta with alpha adaptin and beta' with gamma-adaptin in mammalian cells is likely to depend on the few non-conservative differences between their respective sequences and BAD1. Four of these (one with respect to beta and three versus 105a) are clustered in a particular region (residues 155 to 305), which may therefore represent a domain that influences the choice of partner adaptin. PMID- 8006085 TI - Genetic deficiency in low density lipoprotein receptor-related protein confers cellular resistance to Pseudomonas exotoxin A. Evidence that this protein is required for uptake and degradation of multiple ligands. AB - The low density lipoprotein receptor-related protein (LRP) is a large multifunctional receptor implicated in the cellular uptake of functionally diverse ligands. Biochemical evidence suggests that LRP is a clearance receptor for apoE-rich remnant lipoproteins, lipoprotein lipase, alpha 2 macroglobulin/protease complexes, plasminogen activator/inhibitor complexes, the active protease tissue-type plasminogen activator and exotoxin A from Pseudomonas aeruginosa. Mice genetically deficient in LRP die early during gestation, underscoring the essential physiological role of this gene in vivo. To study the effect of LRP deficiency at the cellular level, we have used Pseudomonas exotoxin A (PEA) to select murine embryonic fibroblasts that are genetically deficient in LRP. Our results demonstrate that this single gene defect is sufficient to confer resistance to PEA on cultured cells. In addition, embryonic fibroblasts lacking LRP are unable to bind, internalize and degrade methylamine-activated alpha 2 macroglobulin and complexes of urokinase with plasminogen activator inhibitor-1. Furthermore, cellular uptake and degradation of receptor-associated protein, a 39 kDa accessory protein of LRP, is reduced by 90% in the absence of LRP. These results provide genetic evidence for the multifunctional nature of LRP and its crucial role in protease/inhibitor complex metabolism. PMID- 8006086 TI - Immunolocalization of microfibril and microfibril-associated proteins in the subendothelial matrix of the developing mouse aorta. AB - In the developing aorta, endothelial cell connecting filaments extend from the abluminal surface of the endothelial cell to the subjacent elastic lamina. The connecting filaments are in alignment with intracellular stress fibers and are oriented parallel to the direction of blood flow. In the present study, the composition of the endothelial cell connecting filaments was investigated by indirect immunogold labeling with antibodies to the microfibril proteins, MP340 (fibrillin) and MAGP, and to fibronectin and heparan sulfate proteoglycan (HSPG). In the subendothelial matrix of both 15-day gestational and 5-day post-natal mouse aortae, the connecting filaments showed moderate immunoreactivity with anti MP340; however, no significant immunoreaction was seen with anti-MAGP. Anti fibronectin strongly labeled the connecting filaments and a weak immunoreaction was seen with anti-HSPG. In contrast, the adjacent 'elastin-associated microfibrils' showed a very strong immunoreaction with anti-MP340 and a moderate reaction with anti-MAGP. Little or no reaction was seen with anti-fibronectin or anti-HSPG. The filaments that connect endothelial cells to the subjacent elastic lamina during aortic development are thus microfibrillar in nature and related to elastin-associated microfibrils as evidenced by their positive immunoreaction with anti-MP340. The absence of labeling with anti-MAGP, however, suggests that either these fibrillin-containing filaments do not contain MAGP or that the immunoreactive epitopes are blocked by the proteins that coat the connecting filaments such as fibronectin. These results suggest that microfibrils not in association with elastin may play a role in cell anchorage and, more specifically, in the aorta may be involved in maintaining the structural integrity of the endothelial cell layer during early development of the vessel wall. Furthermore, the absence of immunoreactivity with anti-MAGP on the fibrillin-containing endothelial cell connecting filaments raises the possibility that microfibrils may consist of a family of related filaments rather than a single structural entity. PMID- 8006087 TI - Differential effects of temperature blockade on the proteolytic processing of three secretory granule-associated proteins. AB - Vesicular transport within the secretory pathway can be arrested by incubating cells at 15 degrees C or 20 degrees C to block exit from the endoplasmic reticulum or trans-Golgi network, respectively. Using this powerful tool we have compared the intracellular sites of endoproteolytic processing of proopiomelanocortin and two prohormone processing enzymes in AtT-20 mouse pituitary corticotrope tumor cells. For comparison, proopiomelanocortin processing was also evaluated in primary neurointermediate pituitary cultures. AtT-20 cells synthesize and store endogenous proopiomelanocortin and prohormone convertase 1; AtT-20 cells expressing high levels of integral membrane or soluble peptidylglycine alpha-amidating monooxygenase were generated by stable transfection. Cells were incubated with [35S]methionine and chased at 4 degrees C, 15 degrees C, 20 degrees C or 37 degrees C. The endoproteolytic processing of peptidylglycine alpha-amidating mono-oxygenase, prohormone convertase 1, and proopiomelanocortin was compared following immunoprecipitation. Endoproteolytic processing of integral membrane and soluble peptidylglycine alpha-amidating monooxygenase proteins was completely blocked by incubation of cells at 20 degrees C. In contrast, prohormone convertase 1 processing from the 87 kDa precursor to the 81 kDa intermediate proceeded to completion at both 15 degrees C and 20 degrees C, while cleavage to generate the 63 kDa prohormone convertase 1 protein was completely blocked at 20 degrees C. In AtT-20 cells and neurointermediate pituitary cultures, generation of beta-lipotropin from proopiomelanocortin continued at a slow but significant rate at 20 degrees C, while processing of beta-lipotropin to beta-endorphin was blocked. Thus prohormone convertase 1 processing begins in the endoplasmic reticulum and is not completed until after the trans-Golgi network, while peptidylglycine alpha amidating monooxygenase processing begins after the trans-Golgi network. Selected proopiomelanocortin cleavages begin before entry into immature granules. PMID- 8006088 TI - Child language research: building on the past, looking to the future. PMID- 8006089 TI - Early object labels: the case for a developmental lexical principles framework. AB - Universally, object names make up the largest proportion of any word type found in children's early lexicons. Here we present and critically evaluate a set of six lexical principles (some previously proposed and some new) for making object label learning a manageable task. Overall, the principles have the effect of reducing the amount of information that language-learning children must consider for what a new word might mean. These principles are constructed by children in a two-tiered developmental sequence, as a function of their sensitivity to linguistic input, contextual information, and social-interactional cues. Thus, the process of lexical acquisition changes as a result of the particular principles a given child has at his or her disposal. For children who have only the principles of the first tier (reference, extendibility, and object scope), word learning has a deliberate and laborious look. The principles of the second tier (categorical scope, novel name-nameless category' or N3C, and conventionality) enable the child to acquire many new labels rapidly. The present unified account is argued to have a number of advantages over treating such principles separately and non-developmentally. Further, the explicit recognition that the acquisition and operation of these principles is influenced by the child's interpretation of both linguistic and non-linguistic input is seen as an advance. PMID- 8006090 TI - Pronoun case overextensions and paradigm building. AB - Pronoun case errors, or overextensions, like *me want it are characteristic of English child language. This paper explores a hypothesis that the morphological structure of a pronoun influences the pattern of these errors. The Language Acquisition Device (LAD) attempts to analyse English pronoun case forms into stems and affixes, but cannot because of their irregularity. Nevertheless the LAD extracts a phonetic core for each pronoun (e.g./m-/ for the 1st sg.,/h-/ for the 3rd masc. sg.). The phonetic core blocks the overextension of suppletive nominative forms like I and she. This hypothesis predicts strong differences in the frequency and types of errors between pronouns with suppletive nominatives and those without. Evidence for this hypothesis was found in a transcript database of twelve children, with data collected in one hour samples every month from 1;0 to 3;0. 20,908 pronouns were examined, 1347 of which were errors. Statistical analyses of these data provide support for this hypothesis. PMID- 8006092 TI - The syntax of questions in child English. AB - The purpose of this article is to provide a contemporary Government-and-Binding (GB) reinterpretation and evaluation of Klima & Bellugi's classic 1966 work on the acquisition of interrogatives. I argue that the central insight of K&B's paper can be captured by positing that wh-questions in Child English involve a wh pronoun positioned in the head complementizer (C) position within the Complementizer Phrase (CP) (so blocking auxiliary inversion if this involves positioning an inverted auxiliary in C) and that in the transition to Adult English, children come to learn that wh-questions involve a wh-phrase superficially positioned in the specifier position within CP. I argue that the wh in-C analysis poses both developmental problems (in that it fails to account for child structures involving a preposed wh-phrase with an uninverted auxiliary) and potential theoretical problems (in that long movement of a wh-head may violate locality principles). I then consider two alternative accounts of wh-questions which posit that wh-movement involves movement of a wh-phrase from the very earliest stages of development. The first of these is an adjunction account, on which wh-phrases are analysed as clausal adjuncts in Child English (adjoined to the Verb Phrase (VP) in the earliest stages and to the Inflection Phrase (IP) in later stages). I note, however, that this provides no principled account of the absence of auxiliary inversion in child wh-questions, and poses continuity problems (especially within a framework such as that of Cinque (1990) in which it is assumed that wh-phrases never adjoin to VP or IP). Finally, I consider an alternative account on which initial wh-phrases are analysed as occupying the specifier position within CP at all stages of development. I note that the problem posed by this analysis is accounting for the absence of auxiliary inversion in early wh-questions, and offer an account which posits that children overgeneralize specifier-head agreement from IP to CP. PMID- 8006091 TI - Sensitivity of children's inflection to grammatical structure. AB - What is the input to the mental system that computes inflected forms like walked, came, dogs, and men? Recent connectionist models feed a word's phonological features into a single network, allowing it to generalize both regular and irregular phonological patterns, like stop-stopped, step-stepped and fling-flung, cling-clung. But for adults, phonological input is insufficient: verbs derived from nouns like ring the city always have regular past tense forms (ringed), even if they are phonologically identical to irregular verbs (ring the bell). Similarly, nouns based on names, like two Mickey Mouses, and compounds based on possessing rather than being their root morpheme, such as two sabertooths, take regular plurals, even when they are homophonous with irregular nouns like mice and teeth. In four experiments, testing 70 three- to ten-year-old children, we found that children are sensitive to such nonphonological information: they were more likely to produce regular inflected forms for forms like to ring ('to put a ring on') and snaggletooth (a kind of animal doll with big teeth) than for their homophonous irregular counterparts, even when these counterparts were also extended in meaning. Children's inflectional systems thus seem to be like adults': irregular forms are tied to the lexicon but regular forms are computed by a default rule, and words are represented as morphological tree structures reflecting their derivation from basic word roots. Such structures, which determine how novel complex words are derived and interpreted, also govern whether words with irregular sound patterns will be regularized: a word can be irregular only if its structure contains an irregular root in 'head' position, allowing the lexically stored irregular information to percolate up to apply to the word as a whole. In all other cases, the inflected form is compouted by a default regular rule. This proposal fits the facts better than alternatives appealing to ambiguity reduction or semantic similarity to a word's central sense. The results, together with an analysis of adult speech to children, suggest that morphological structure and a distinction between mechanisms for regular and irregular inflection may be inherent to the design of children's language systems. PMID- 8006093 TI - Exploring the boundary between syntax and pragmatics: relevance and the binding of pronouns. AB - This paper explores the interface between syntax and pragmatics, focusing on the binding of pronouns and the pragmatics of the paradigms used to test this aspect of syntactic knowledge. Reinhart's (1986) version of Binding Theory (which accords a specific role to pragmatics in processes of pronoun resolution) and Sperber & Wilson's (1986) Theory of Relevance are used to examine the syntax and pragmatics of pronoun interpretation. A set of predictions based on Relevance Theory are evaluated against published results of tests of Binding Theory. The paper concludes that Relevance Theory provides a means of understanding constraints on testing syntactic knowledge and argues that pragmatic factors must be systematically controlled in any evaluation of syntactic knowledge. PMID- 8006094 TI - Speech-like vocalizations in infancy: an evaluation of potential risk factors. AB - This work reports longitudinal evaluation of the speech-like vocal development of infants born at risk due to prematurity or low socio-economic status (SES) and infants not subject to such risk. Twenty infants were preterm (10 of low SES) and 33 were full term (16 of low SES), and all were studied from 0;4 through 1;6. The study provides the indication that at-risk infants are not generally delayed in the ability to produce well-formed speech-like sounds as indicated in tape recorded vocal samples. At the same time, premature infants show a tendency to produce well-formed syllables less consistently than full terms after the point at which parents and laboratory personnel note the onset of the canonical babbling stage (the point after which well-formed syllables are well established in the infant vocal repertoires). Further, even though low SES infants produce well-formed speech-like structures on schedule, they show a reliably lower tendency to vocalize in general, as reflected by fewer utterances per minute in recorded samples. PMID- 8006095 TI - The (non)realization of unstressed elements in children's utterances: evidence for a rhythmic constraint. AB - In this study it is argued that the omission of closed class morphemes and of unstressed syllables within words is related to their common characteristic, viz. that they are unstressed, rhythmically weak parts of utterances. Several strands of evidence indicate that it is unlikely that children are unable to perceive these elements in the input speech. The pattern of (non)realization of unstressed syllables within content words and the class of determiners, was analysed in two Dutch children from 1;6 to 2;11. It appeared that polysyllabic words were quite generally truncated in such a way that they fitted a trochaic (strong-weak) pattern, particularly in the early samples. Some observations with respect to the (non)realization of determiners are suggestive of an influence of an SW constraint on the realization of noun phrases. These findings support the hypothesis that in the course of utterance preparation, words and phrases are mapped onto S(W) templates. Anecdotal evidence suggests that the dissolution of the SW-constraint coincides with the acquisition of specific aspects of stress assignment in Dutch, such as quantity sensitivity. PMID- 8006096 TI - Developmental and stylistic variation in the composition of early vocabulary. AB - Results are reported for stylistic and developmental aspects of vocabulary composition for 1,803 children and families who participated in the tri-city norming of a new parental report instrument, the MacArthur Communicative Development Inventories. We replicate previous studies with small samples showing extensive variation in use of common nouns between age 0; 8 and 1;4 (i.e. 'referential style'), and in the proportion of vocabulary made up of closed-class words between 1;4 and 2;6 (i.e. 'analytic' vs. 'holistic' style). However, both style dimensions are confounded with developmental changes in the composition of the lexicon, including three 'waves' of reorganization: (I) an initial increase in percentage of common nouns from 0 to 100 words, followed by a proportional decrease; (2) a slow linear increase in verbs and other predicates, with the greatest gains taking place between 100 and 400 words; (3) no proportional development at all in the use of closed-class vocabulary between 0 and 400 words, followed by a sharp increase from 400 to 680 words. When developmental changes in noun use are controlled, referential-style measures do not show the association with developmental precocity reported in previous studies, although these scores are related to maternal education. By contrast, when developmental changes in grammatical function word use are controlled, high closed-class scores are associated with a slower rate of development. We suggest that younger children may have less perceptual acuity and/or shorter memory spans than older children with the same vocabulary size. As a result, the younger children may ignore unstressed function words until a later point in development while the older children tend to reproduce perceptual details that they do not yet understand. Longitudinal data show that early use of function words (under 400 words) is not related to grammatical levels after the 400-word point, confirming our 'stylistic' interpretation of early closed-class usage. We close with recommendations for the unconfounding of stylistic and developmental variance in research on individual differences in language development, and provide look-up tables that will permit other investigators to pull these aspects apart. PMID- 8006097 TI - Is nativism sufficient? AB - The past and present state of the empiricism-nativism issue is analysed. Empiricist philosophical doctrine ('no innate ideas') distinguished idea from structure or mechanism. However, Chomsky's conception of innate linguistic universals erased this distinction. The elimination left would-be empiricists without a coherent and defensible position. I argue that the issue remains alive primarily because of tension between two scientific tasks that face students of development. One is to discover what is cognitively and linguistically primitive, a task that encourages nativism. However, nativism is ultimately unsatisfactory because it systematically neglects the other task, which is to account for development, including the emergence of postulated innate primitives. To account for such primitives, it is necessary to relate them to particular central nervous system structures in such a way as to explain how the structure has the particular cognitive effects that define the primitive. That is likely to be difficult, and I show how the study of learning--much neglected in recent years- can help by reducing the number and type of innate primitives whose origin must be explained in that way. PMID- 8006098 TI - High-performance liquid chromatography-thermospray mass spectrometry of epoxy polyunsaturated fatty acids and epoxyhydroxy polyunsaturated fatty acids from an incubation mixture of rat tissue homogenate. AB - A method for the analysis of epoxy polyunsaturated fatty acids (EpPUFAs) and epoxyhydroxy polyunsaturated fatty acids (EpHPUFAs) in rat tissue homogenate, with homo-gamma-linolenic acid (20:3, n - 6), arachidonic acid (20:4, n - 6), eicosapentaenoic acid (20:5, n - 3) or docosahexaenoic acid (22:6, n - 3) as a substrate, has been developed. Extraction with dichloromethane at pH 4-5 and concentration in the presence of pyridine were performed. Spectral analysis of chromatograms obtained with high-performance liquid chromatography-thermospray mass spectrometry showed the presence of EpPUFAs, EpHPUFAs and dihydroxy metabolites (DiHPUFAs) of EpPUFAs corresponding to each precursor fatty acid. On a selected-ion monitoring chromatogram, many EpPUFAs, EpHPUFAs and DiHPUFAs in an extract from an incubation mixture of each precursor fatty acid in aged rat tissue homogenate were detected simultaneously within 70 min. EpPUFAs and DiHPUFAs derived from 20:3 (n - 6) or 20:5 (n - 3) were detected in significant amounts. From these results, a highly active cytochrome P450 system or non enzymic oxidative reactions in aged rat tissue homogenate were suggested. PMID- 8006099 TI - Simultaneous measurement of the cell-differentiating agent hexamethylene bisacetamide and its metabolites by gas chromatography. AB - Hexamethylene bisacetamide (HMBA) is a potent in vitro differentiating agent that has clinical potential as an anticancer drug both as a single agent and as a component of combination therapy. A sensitive and efficient GC method for the isolation, derivatization, and measurement of both HMBA and its two major metabolites in plasma and urine in a single analysis is described. In situ carbamylation of the biological sample with diethylpyrocarbonate forms the urethane derivative of the basic N-acetyl diaminohexane metabolite and allows analyte isolation and concentration by solid-phase extraction. Subsequent formation of the n-butyl ester of 6-acetamidohexanoic acid, the major metabolite, provides a derivatized biological extract that can be rapidly analyzed by temperature-programmed GC. The quantitative extraction and the efficient derivatization steps provide a limit of quantitation of 0.05 mM (10 micrograms/ml) for all analytes with a precision better than 8% for the range of in vitro activity (0.1-2.0 mM). This method is amenable to automation and is well suited for the analysis of clinical samples. PMID- 8006101 TI - High-performance liquid chromatographic method for the quantitative determination of butorphanol, hydroxybutorphanol, and norbutorphanol in human urine using fluorescence detection. AB - A sensitive, quantitative reversed-phase high-performance liquid chromatographic method has been established for the simultaneous determination of butorphanol, a synthetic opioid, and its metabolites, hydroxybutorphanol and norbutorphanol, in human urine samples. The method involved extraction of butorphanol, hydroxybutorphanol, and norbutorphanol from urine (1.0 ml), buffered with 0.1 ml of 1.0 M ammonium acetate (pH 6.0), onto 1-ml Cyano Bond Elut columns. The eluent was evaporated under nitrogen and low heat, and reconstituted with the HPLC mobile phase, acetonitrile-methanol-water (20:10:70, v/v/v), containing 10 mM ammonium acetate and 10 mM TMAH (pH 5.0). The samples were chromatographed on a reversed-phase octyl 5-microns column. The analysis was accomplished by detection of the fluorescence of the three analytes, at excitation and emission wavelengths of 200 nm and 325 nm, respectively. The retention times for hydroxybutorphanol, norbutorphanol, the internal standard, and butorphanol were 5.5, 9.0, 13.0, and 23.4 min respectively. The validated quantitation range of the method was 1-100 ng/ml for butorphanol and hydroxybutorphanol, and 2-200 ng/ml for norbutorphanol in urine. The observed recoveries for butorphanol, hydroxybutorphanol, and norbutorphanol were 93%, 72%, and 50%, respectively. Standard curve correlation coefficients of 0.995 or greater were obtained during validation experiments and analysis of study samples. The method was applied on study samples from a clinical study of butorphanol, providing a pharmacokinetic profiling of butorphanol. PMID- 8006100 TI - Direct gradient reversed-phase high-performance liquid chromatographic determination of salicylic acid, with the corresponding glycine and glucuronide conjugates in human plasma and urine. AB - A gradient reversed-phase HPLC analysis for the direct measurement of salicylic acid (SA) with the corresponding glycine and glucuronide conjugates in plasma and urine of humans was developed. The glucuronides were isolated by preparative HPLC from human urine samples. The concentration of the glucuronides in the isolated fraction were determined after enzymatic hydrolysis. Salicylic acid acyl glucuronide (SAAG) was not present in plasma. No isoglucuronides were present in acidic and alkaline urine of the volunteer. The limits of quantitation in plasma are: SA 0.2 microgram/ml, salicyluric acid (SU) 0.1 microgram/ml, salicylic acid phenolic glucuronide (SAPG) 0.4 microgram/ml and salicyluric acid phenolic glucuronide (SUPG) 0.2 microgram/ml. The limit of quantitation in urine is for all compounds 5 micrograms/ml. Salicylic acid acyl glucuronide is stable in phosphate buffer pH 4.9 during 8 h at 37 degrees C; thereafter it declines to 80% after 24 h. The subject's urine was therefore acidified by the oral intake of 4 x 1.2 g of ammonium chloride/day. With acidic urine, hardly any salicylic acid is excreted unchanged (0.6%). It is predominantly excreted as salicyluric acid (68.7%). PMID- 8006102 TI - Stereospecific and simultaneous high-performance liquid chromatographic assay of flosequinan and its metabolites in human plasma. AB - A high-performance liquid chromatographic method was developed for the simultaneous determination of the enantiomers of flosequinan [(+/-)-7-fluoro-1 methyl-3-methylsulphinyl-4-quinolone] and its metabolites, flosequinan sulphide and sulphone, in human plasma. These compounds were extracted from plasma with chloroform. The compounds were separated on a chiral stationary phase of cellulose tris-3,5- dimethylphenylcarbamate coated on silica gel, with a mobile phase of ethanol-methanol (22:78, v/v). Flosequinan enantiomers and flosequinan sulphone were determined by UV detection at a wavelength of 320 nm. Flosequinan sulphide was determined using fluorescence detection (excitation at 370 nm, emission at 430 nm). Standard curves were linear over the concentration range 5 10,000 ng/ml for both enantiomers and flosequinan sulphide, and 20-10,000 ng/ml for flosequinan sulphone. This method is adequate for pharmacokinetic studies of the enantiomers of flosequinan and its metabolites. PMID- 8006103 TI - Assay of the antiangiogenic compound TNP-470, and one of its metabolites, AGM 1883, by reversed-phase high-performance liquid chromatography in plasma. AB - This paper describes a reversed-phase, high-performance liquid chromatographic (HPLC) method for the isolation, detection, and quantification of TNP-470 (I) and one of its active metabolites, AGM-1883 (II), from plasma. These compounds are initially extracted from plasma with an organic solvent and then separated from one another on a C18 column. Those fractions eluting from the C18 column and containing either I or II are then derivatized through their epoxide moieties with sodium 8-quinolinethiolate (SQT). This derivatization produces fluorescent species that are isolated and quantified by a second reversed-phase HPLC analysis. The assay yields a lower limit of reliable quantification of 2.5 ng/ml and is linear to a concentration at least as high as 160 ng/ml. The inter-assay percent coefficient of variation is less than 18%. PMID- 8006104 TI - High-performance liquid chromatographic method for the separation of chlorambucil and its N-oxide prodrug. AB - A reversed-phase high-performance liquid chromatographic method is described to distinguish chlorambucil N-oxide from the parent chlorambucil and quantitate both after separation from biological samples. The influence of solvent pH, alcohol, acid and ion-pairing agent on the separation is described. The stability of chlorambucil and its N-oxide in buffers and alcohols, as well as stability during filtration is discussed with potential application for metabolic studies. PMID- 8006105 TI - Determination of cisplatin and cis-diammineaquachloroplatinum(II) ion by liquid chromatography using post-column derivatization with diethyldithiocarbamate. AB - A post-column derivatization method has been developed for the determination of cisplatin and its monohydrated form. Cisplatin was isolated on a strong anion exchange column, while a strong cation-exchange column was used for the monohydrated complex. Diethyldithiocarbamate was used as reagent and the influence of temperature, pH and methanol content on the yield of derivative was investigated. The reaction was quantitative using a packed-bed reactor with a surrounding temperature of 115 degrees C and a mobile phase consisting of 0.125 M succinic acid-sodium hydroxide buffer pH 5.2 and methanol (2:3, v/v). The resulting complex, Pt(DDTC)2, was monitored photometrically at 344 nm. The precision of the determination was 11.5% (C.V.) at an injected amount of 20 ng (n = 12) for monoaqua and 8.0% (C.V.) at 9 ng (n = 10) for cisplatin. The method was used to evaluate the plasma concentration of cisplatin and its monohydrated form in a patient. PMID- 8006106 TI - High-performance liquid chromatographic assay for the measurement of atovaquone in plasma. AB - A rapid and efficient isocratic high-performance liquid chromatographic assay for the measurement of atovaquone in plasma has been developed and validated. The drug was extracted from plasma with organic solvents, assayed on a C1 column with a mobile phase of methanol-0.1% acetic acid (70:30, v/v), and detected by ultraviolet absorbance at 254 nm. Recovery of atovaquone from plasma was greater than 85%. Intra- and inter-assay variability were less than 8%, and the average accuracy of the assay (expressed as % bias) ranged from -7.4 to + 2.2%. The upper and lower limits of quantitation were 100 and 0.25 microgram/ml, respectively. Measurement of atovaquone in spiked plasma control samples during routine runs of clinical trial samples confirmed the reliability of the assay. PMID- 8006107 TI - Determination of seven prostanoids in 1 ml of urine by gas chromatography negative ion chemical ionization triple stage quadrupole mass spectrometry. AB - In an isotope dilution assay, prostaglandin (PG) E2, 6-keto-PGF1 alpha, thromboxane (Tx) B2 and their metabolites PGE-M (11 alpha-hydroxy-9,15-dioxo 2,3,4,5,20-pentanor-19-carboxyprostano ic acid), 2,3-dinor-6-keto-PGF1 alpha, 2,3 dinor-TxB2 and 11-dehydro-TxB2 were determined in urine by gas chromatography triple stage quadrupole mass spectrometry (GC-MS-MS). After addition of deuterated internal standards, the prostaglandins were derivatized to their methoximes and extracted with ethyl acetate-hexane. The sample was further derivatized to the pentafluorobenzylesters and purified by thin-layer chromatography (TLC). Three zones were scraped from the TLC plate. The prostanoid derivatives were converted to their trimethylsilyl ethers and the products were quantified by GC-MS-MS. In each run, two or three prostanoids were determined. PMID- 8006109 TI - Processing of envelope polypeptides of herpes simplex virus type 1. Demonstration of variation in different cell lines by high-performance liquid chromatography and radioimmunoprecipitation. AB - [35S]Methionine-labelled envelope polypeptides of herpes simplex virus type 1, strain F, propagated in mammalian cell culture of various origins, were separated by ion-exchange high-performance liquid chromatography on a TSK DEAE-3SW column. Analysis of the fractions by radioimmunoprecipitation followed by sodium dodecyl sulphate polyacrylamide gel electrophoresis of the immunoprecipitates showed similarities as well as distinct differences in the number, migration patterns and molecular mass of the synthesized polypeptides, depending on the host cell. The results show that this method can be used to demonstrate species-specific or organ-specific differences in the processing of virus-specified polypeptides synthesized in host cells. PMID- 8006108 TI - Measurement of GABA in rat brain microdialysates using o-phthaldialdehyde sulphite derivatization and high-performance liquid chromatography with electrochemical detection. AB - A number of recent studies have detected gamma-aminobutyric acid (GABA) in brain microdialysates by measuring an electroactive o-phthaldialdehyde (OPA)-alkylthiol derivative using HPLC with electrochemical detection. A particular problem of this approach is the stench of the thiol reagents involved, and the poor stability of the electroactive GABA derivative. Here we report that these practical disadvantages can be overcome by substitution of the OPA-alkylthiol reaction with an OPA-sulphite reaction. This provides a simple, sensitive and reliable means for determination of GABA in microdialysates of rat brain. PMID- 8006110 TI - Determination of the calcium antagonist SIM6080 in plasma by high-resolution gas chromatography. AB - A sensitive and selective gas chromatographic method for the determination of the calcium antagonist SIM6080 in plasma has been developed and validated. A three step extraction procedure is employed followed by capillary gas chromatographic analysis using nitrogen-selective detection and the programmed temperature vaporizer injection technique. The defluorinated analogue was used as the internal standard. The analysis of spiked plasma demonstrated the good accuracy and precision of the method with limit of detection of 1 ng/ml. The method has been used for pharmacokinetic studies in laboratory animals. PMID- 8006111 TI - The detection of tomato spotted wilt virus using the polymerase chain reaction. AB - A polymerase chain reaction (PCR) based assay was used to detected a number of UK tomato spotted wilt virus (TSWV) isolates in total RNA extractions made from infected plant material. Extracts were reverse transcribed and the resultant cDNA amplified by PCR, using oligonucleotide primers specific for a 276 base pair fragment of the L RNA segment. Assay products were electrophoresed on agarose gels and visualised by ethidium bromide staining. The viral origin of the product produced was confirmed by sequencing, with the data obtained having very high homology with previously published L RNA sequence data. The specificity and sensitivity of the RT-PCR assay, in comparison with existing tests, is discussed. PMID- 8006113 TI - A simple method for obtaining highly viable virus from culture supernatant. AB - Traditionally density-gradient methods are used to purify viruses. However, these procedures are not only time consuming and cumbersome, recovery of viable viruses are often quite low. In this report, a single-step concentration technique was used to concentrate a mutant of Moloney murine leukemia virus (ts1) virus from culture supernatants by ultrafiltration. A special ultrafiltration unit with a 100,000 mol wt cut-off was able to concentrate viruses about 30-fold without losing any infectivity. In comparison, traditional sucrose density gradient purified viruses lost a significant portion of their infectivity. This technique could be used for concentrating other viruses for many useful purposes where more viable viruses are needed, e.g., study of virus-cell binding. PMID- 8006112 TI - Detection of HIV-p24 antigen in body fluids by immunotrapping on Staphylococcus aureus (Cowan 1) bacteria, gold immunolabelling and backscattered electron analysis in a scanning electron microscope. AB - An immunosorbent electron microscopical (ISEM) method, the Protein A-coated bacteria technique/gold, (PA-CBT/G), was developed for the detection of non particulate soluble antigens. The method is based on immunotrapping of antigens on antibody coated, glutaraldehyde cross-linked, Protein A-rich, Staphylococcus aureus bacteria. The 'trapped' antigen is then identified by colloidal-gold immunolabelling. Gold particles are observed in a scanning/transmission electron microscope by analysis of backscattered electrons. With this method it was possible to detect the presence of p24 HIV antigens in blood, semen, saliva, crevicular and cerebrospinal fluids from HIV seropositive cases. Although the PA CBT/G identified correctly the p24 antigen in only 80% of the ELISA HIV-antigen positive sera, it detected, more frequently than ELISA, HIV-antigen in seminal and oral fluids. The PA-CBT/G method could thus be useful to fully characterise individual HIV excretion patterns in body fluids other than sera even from patients negative for HIV-antigen by ELISA. PMID- 8006114 TI - Josef Warkany, 1902-1992: a personal remembrance. PMID- 8006115 TI - Prenatal smokeless tobacco effects on the rat fetus. AB - The objective of this study was to examine the effect of an aqueous extract of smokeless tobacco (ST) on the development and bone ossification of the Sprague Dawley rat fetus at known nicotine blood levels. Dams were intubated with the ST extract three times daily on gestational days (GD) 6-18 with one of the following: ST equivalent to either 1.33 mg nicotine/kg body weight (STD-1), 6 mg nicotine/kg body weight (STD-2), or equal amounts of distilled water (sham treated controls). Parallel groups of rats were used for nicotine-blood-level determinations. Dams were killed on GD 19, fetuses and placentas were weighed, and resorptions, deaths, and/or malformations were noted. Two thirds of the fetuses were further examined by Wilson's method, and the remaining one third was stained and cleared for skeletal examinations. Mean plasma nicotine levels, determined in a parallel group of nonpregnant/pregnant rats, were 220.4/283.3 ng/ml in the STD-1 group and 869.1/846.3 ng/ml in the STD-2 group. At these ST dosages, weight gain of dams was reduced in comparison with sham-treated controls (P < .05), but fetal weights were reduced in the STD-2 group only. Placental weights, litter size, resorptions, deaths, and malformations were not significantly affected. Skeletal examinations revealed several dose-related differences between the ST-treated and sham-treated control groups. In the STD-1 group, reductions in ossification were seen in the nasal and femur width measurements only. In the STD-2 group, reductions in ossification were seen in femur length and width, in the number of ossification centers in the forelimb, in the maxillary, mandibular, and nasal bone measurements. We conclude that under these experimental conditions the effects of ST at the low dose are minimal, whereas the high ST dose resulted in significant growth retardation and decreased ossification levels (P < .05). PMID- 8006116 TI - Presence of dentin phosphoprotein in molars of a patient with dentinogenesis imperfecta type II. AB - Dentin phosphoprotein (DPP) is the major noncollagenous protein component of the dentin extracellular matrix. This highly acidic phosphorylated protein is solely expressed by the ectomesenchymal-derived odontoblast cells of the tooth organ. Several biochemical studies have suggested diminished levels of, or even the absence of, this protein, which is associated with the human genetic disease dentinogenesis imperfecta (DGI) type II. However, more recent molecular studies have established that the DPP gene locus is not localized to the region of human chromosome 4 (4q13-q21), where several previous linkage analysis studies have mapped DGI types II and III. The purpose of this study was to determine the presence or absence of DPP in the dentition of a patient affected with DGI type II using a sensitive and specific immunodetection method with a polyclonal antibody against mouse DPP. Our results indicate that a 95-kDa protein, immunologically crossreactive with the DPP antibody, was detected within the dentin extracellular matrix of molars isolated from both a proband affected with DGI-II and from an age-matched normal individual. In addition, both DGI-II and normal individuals showed comparable DPP in situ degradation associated with dentin extracellular matrix maturation. These results strongly support the hypothesis that the DPP structural gene does not produce the gene product primarily responsible for the human genetic disease DGI type II. PMID- 8006117 TI - Morphological changes during survival, cellular transformation, and calcification of the embryonic mouse: Meckel's cartilage transplanted into heterotopic sites. AB - Meckel's cartilages obtained from 18-day-old embryonic mice were transplanted into heterotopic sites to examine their site-specific effects on cellular modification, calcification, and long-term survival. The explants were isografted into the liver, subcutaneous tissue, anterior chamber of the eye, kidney, peritoneal cavity, and intrafemoral muscle of mouse for up to 2 weeks. In addition, Meckel's cartilages were wrapped in a Nucleopore filter and transplanted into the spleen. Grafted Meckel's cartilages were observed by light and electron microscopy, including application of von Kossa's reaction and osmium potassium ferrocyanide fixation. It was demonstrated by von Kossa's reaction that when Meckel's cartilage was grafted in liver parenchyma, initial calcification appeared on the territorial matrix as spotted deposits. The chondrocytes gradually transformed into small ovoidal cells and showed a morphology closely resembling that of osteocytes. Transplants in the kidney subcapsular site contained active surviving chondrocytes, and subcutaneously grafted Meckel's cartilage revealed three types of chondrocytes: nonhypertrophic and calcification inducing hypertrophic chondrocytes, as well as cells showing osteocytelike phenotypes. Intraocular and Nucleopore filter-wrapped explants showed degenerative changes, and peritoneal-cavity transplants showed cellular hypertrophy, but calcified precipites were not observed. The present investigation demonstrated that in blood-rich tissues Meckel's cartilage showed long-term survival and could modulate calcified precipitation. Thus, this adaptation of Meckel's cartilage to the environment of various heterotopic sites suggests that it has the ability to induce calcification. PMID- 8006118 TI - Effects of prenatal exposure to tobacco smoke on developmental stability in children. AB - The effects of maternal and paternal smoking on fetal and neonatal dental development were investigated in a sample of 199 school children. Fluctuating asymmetry was evaluated in the maxillary arcades of four groups of children: those whose mothers had smoked, those whose fathers had smoked, those whose parents both had smoked, and finally, those whose parents had not smoked. When the magnitudes of fluctuating asymmetry in children exposed to parental tobacco smoke from one parent only were compared with the control group, no general univariate differences were found. Children exposed to smoke from both parents, however, showed significantly elevated levels of asymmetry in four out of six comparisons. In contrast, an analysis of variance failed to find significant differences on the basis of sex, parity, smoking status, or their interactions. It is concluded that parental smoking does not result in developmental destabilization of the fetus and neonate. PMID- 8006119 TI - Unusual cranial aspects of the Apert syndrome. AB - Frank cloverleaf skull is found in approximately 4% of Apert-syndrome infants. However, the usual Apert skull and its cloverleaf form are spectral in nature. In all patients, the temporal bones are obliquely situated, and the degree to which this is so determines whether no, mild, moderate, or severe cloverleafing will occur. True encephalocele rarely is found in the Apert syndrome, but pseudoencephalocele in the frontal region sometimes is confused with it. Because the Apert calvaria at birth is characterized by a widely gaping midline defect, the midfrontal region of the brain is not covered by bone during early infancy. However, with time, closure of the midline defect occurs by coalescence of bony islands, thus covering the pseudoencephalic region. Also discussed in this paper are (a) atypical calvarial development with patency of the coronal sutures in one case, (b) size and position of the temporal muscles, and (c) size and position of the superficial temporal fat pads. PMID- 8006120 TI - Facial growth and development during puberty in unilateral cleft lip and palate: a longitudinal study. AB - Roentgencephalometry was used for longitudinal assessment of facial growth and development in 20 boys and 23 girls (age range 10-15 years), with complete unilateral cleft lip and palate. A marked limitation of growth showed the depth of the upper jaw and the height of the upper lip whereas the most intense growth was present in variables characterizing the prominence of the nose. The growth rate was always higher in boys than in girls who had a more pronounced prognathia of the lower jaw. However, the development of the face proceeded identically in both sexes. In contrast with the increasing protrusion of the lower jaw was the increase of the retrusion of the upper jaw, and this led to a flattening of the facial profile and an impairment of sagittal jaw relations. The excessively steep mandibular body and the vertical disproportion of the face remained unchanged. Sagittal jaw relations deteriorated in three fourths of the patients, facial convexity in more than 90%, and neither condition showed any signs of improvement. It was possible to maintain the overjet at the same level as it was at the beginning of puberty; an improvement was attained with fixed appliances. The little scatter of developmental changes of mandibular rotation and the assessment of some correlations were suggestive of an individually constant postoperative character of facial development in clefts. Correlation coefficients disclosed that a more unfavorable condition at the age of 10 years did not imply a subsequent more marked deterioration of development during puberty. Mandibular rotation was not correlated with facial convexity, sagittal jaw relations, or overjet. The possibility of an improvement of overjet by the use of removable appliances was limited by the development of the ANB angle. The use of fixed appliances led to a reduction of this limitation. PMID- 8006121 TI - Dental arch dimensions in unoperated adult cleft-palate patients: an analysis of 37 cases. AB - In surgically treated patients with clefts of the lip, alveolus, and/or palate, the vertical, transversal, and sagittal development of the maxilla is influenced by intrinsic, functional, and iatrogeneous (surgical) factors. To evaluate the effect of intrinsic and functional factors on dental arch development, we examined and compared unoperated adult individuals with different types of clefts. Dental casts of 37 Indonesian adults with unoperated unilateral clefts were studied: 15 subjects with unilateral cleft lip and alveolus (median age: 24 years) and 22 subjects with complete unilateral cleft of lip, alveolus, and palate (median age: 25 years). Dental arch dimensions were measured and evaluations of arch form were made. The Student's t-test showed that arch width and arch depth were significantly smaller in the complete-cleft group. There is a tendency for the smaller segment to be positioned more cranially in the complete cleft group. Our conclusion was that subjects with an unoperated complete-cleft lip, alveolus, and palate develop an arch form that is significantly different from that in subjects with unoperated cleft lip and alveolus. PMID- 8006122 TI - Craniofacial abnormalities in animal models of mucopolysaccharidoses I, VI, and VII. AB - The genetic mucopolysaccharidoses (MPS) are a family of lysosomal storage diseases resulting from the partial catabolism of several glycosaminoglycans (GAGs). Depending on the particular enzyme deficient in activity, the MPS syndromes are defined into groups MPS I through VII, with several subgroups for a total of 10 disorders. In humans, clinical features include dysostosis multiplex, hepatosplenomegaly, hypertelorism, macroglossia, hypoplastic and irregularly shaped teeth, hyperplastic lips and gingiva, facial dysmorphia, corneal clouding, and mental retardation. MPS I (alpha-L-iduronidase deficiency) and VI (arylsulfatase B deficiency) have been described in cats, MPS VII (beta glucuronidase deficiency) in dogs. Biochemically, these syndromes appear the same as their human counterparts and have similar clinical characteristics. All are inherited as autosomal recessive traits. The purpose of this study was to analyze the craniofacial aspects of these diseases in the animal models and compare these data with descriptions of the human syndromes. A total of 28 live animals were examined. Thirty-one skulls prepared from postmortem specimens were measured directly and radiographed. Controls were closely related family members of the same sex and similar age without the disease, clinically or biochemically. The data indicated that, as in the human syndromes, each is distinct, and the skull bones most severely affected are those of endochondral origin. PMID- 8006123 TI - Retrograde ejaculation. AB - Retrograde ejaculation is an uncommon cause of male infertility. It should be suspected in any case of azoospermia, and might be congenital, acquired or idiopathic in origin. When pharmacological attempts to restore anterograde ejaculation fail, it is suggested that spermatozoa should be recovered from post ejaculation urine to be applied in one of the modern techniques of assisted reproduction. The successful recovery of viable spermatozoa from the urine is dependent upon careful regulation of pH and osmolarity of the urine at the time of ejaculation. Careful handling of the retrieved spermatozoa enables isolation of sperm cells with good quality for insemination of ovulated oocytes (in vivo) or retrieved oocytes (in vitro). PMID- 8006125 TI - Conversion of cycles involving ovarian hyperstimulation with intra-uterine insemination to in-vitro fertilization. AB - Conversion to in-vitro fertilization (IVF) and embryo transfer as an alternative to cancellation was offered in 27 consecutive cycles of controlled ovarian hyperstimulation and intra-uterine insemination (IUI) cycles with excessive follicular development in patients with idiopathic infertility. IVF and embryo transfer was performed in 25 cycles, resulting in 13 pregnancies (52%), with 22% of couples having at least two embryos cryopreserved. The pregnancies have resulted in one singleton and two twin births, one spontaneous abortion, and nine ongoing pregnancies (including one triplet gestation). Four patients developed severe ovarian hyperstimulation syndrome (OHSS) after IVF and embryo transfer, including two cases requiring paracentesis. Three of four OHSS patients were pregnant, resulting in live births of healthy twins, one spontaneous abortion and one ongoing singleton gestation. In two cycles a spontaneous luteinizing hormone (LH) surge occurred, preventing oocyte retrieval. For these two women, drainage of all follicles except the five most likely to fertilize (18-22 mm diameter) was performed, followed by IUI, with no pregnancies or OHSS observed. Conversion of patients from IUI cycles to IVF/embryo transfer cycles avoids cancellation of the very cycles with the best chance of achieving pregnancy. OHSS remains a problem, necessitating extensive pre-IVF counselling and post-transfer vigilance. PMID- 8006126 TI - The artificial cycle as an effective treatment of persistently retarded endometrium in the luteal phase. AB - The objective of this study was to examine the results of two hormonal treatment modalities on subjects who had persistently abnormal endometrial development in the luteal phase. A prospective study design was used to investigate 14 women who had persistently retarded endometrium associated with infertility (n = 11) or recurrent miscarriage (n = 3). Treatment A consisted of progesterone supplementation in the form of i.m. progesterone at a daily dose of 25-50 mg starting on day luteinizing hormone (LH) + 1 for 14 days. Treatment B consisted of artificial cycles produced after down-regulation of the hypothalamic-pituitary ovarian axis with Goserelin (3.6 mg s.c.) followed by the administration of a standard hormone replacement therapy. Endometrial biopsy was taken on day 19 of the artificial cycle or days LH + 5 to +7 in the progesterone supplementation cycle. A histological study was made of the endometrial specimens by standard dating criteria and morphometry. The artificial cycle resulted in normal development in all subjects (n = 11), whereas progesterone supplementation restored normal endometrial development in only seven of 11 (64%) subjects. We conclude that persistently retarded endometrium could be treated more effectively with the artificial cycle than with progesterone supplementation. PMID- 8006124 TI - Placental protein 14 in cycles with normal and retarded endometrial differentiation. AB - The purpose of this study was to investigate whether endometrium with retarded development differs, functionally, from endometrium with normal 'in-phase' development. Precisely timed endometrial biopsies were obtained from 24 women suffering from unexplained infertility at 4, 7, 10 and 13 days following the luteinizing hormone (LH) surge. Frozen sections were labelled with an anti placental protein (PP) 14 monoclonal antibody using an avidin-biotin peroxidase technique and semi-quantification of endometrial PP14 was performed using a Quantimet 970 image analyser. Serum PP14 and saliva progesterone were measured for each patient. Data were analysed using one- and two-way analysis of variance. Normal and retarded endometrium were identified in 16 (group I) and eight (group II) women respectively. Both groups demonstrated a significant increase of the area of precipitate measured for PP14 from day LH + 4 to LH + 13. However, two way analysis of variance showed that endometrial PP14 was significantly (P < 0.05) lower in the retarded endometrium group at LH + 10 and LH + 13. Serum PP14 was also significantly lower (P < 0.01) in women with retarded endometrial development at LH + 13. Women with normal endometrial development had a significantly higher (P < 0.05) concentration of cumulative saliva progesterone from LH + 3 to LH + 5. This study indicates that there are functional differences between normal and retarded endometrium. These differences may adversely affect uterine receptivity during implantation and the early placentation stage. PMID- 8006127 TI - Induction of ovulation in rabbits by pure urinary luteinizing hormone. AB - In 18-week-old nulliparous rabbit does, ovulation was induced with 50 IU of pure urinary luteinizing hormone (LH; LH group), or 50 IU of human chorionic gonadotrophin (HCG; HCG group), in order to determine the effect of these treatments on 17 beta-oestradiol and progesterone concentrations, and on oocyte and embryo quality. Luteinizing follicles, recovered oocytes, progesterone concentration and grade 5 embryos were significantly reduced when pure urinary LH was used. Statistically significant correlations were found: (i) between oestradiol concentration and number of degenerated oocytes in both groups (positive); (ii) between oestradiol concentration and grade 1 and 2 embryos (negative), and grade 5 embryos (positive) in the HCG group; (iii) between progesterone concentration and metaphase II oocytes (negative), and between progesterone and grade 5 embryos (positive), in the HCG group; and (iv) between progesterone and oestradiol concentrations (negative) in the LH group. It seems that the oestradiol to progesterone ratio improves during the early luteal phase when ovulation is induced with LH, and that oestradiol and progesterone concentrations could play a role in determining oocyte and embryo quality. PMID- 8006128 TI - Induction of pre-ovulatory luteinizing hormone surge by gonadotrophin-releasing hormone agonist for women at risk for developing the ovarian hyperstimulation syndrome. AB - Ovarian hyperstimulation syndrome (OHSS) is a major risk in patients undergoing ovulation induction protocols. Withholding injection of human chorionic gonadotrophin (HCG) may prevent the development of OHSS, but can also result in failure to ovulate and conceive. We have used a gonadotrophin-releasing hormone agonist (GnRHa) as an alternative to HCG in women not undergoing in-vitro fertilization in an attempt to prevent OHSS. The study included 12 cycles in 12 women scheduled for ovulation induction with human menopausal gonadotrophin (HMG) who were at risk of developing OHSS (oestradiol > 3500 pg/ml, number of follicles > 20). GnRHa was injected to induce the pre-ovulatory, luteinizing hormone surge which triggers follicular maturation. Progesterone was administered for luteal support. Six pregnancies were achieved, and none of the 12 women developed OHSS. Since the pregnancy rate in this study was acceptable, we can recommend the use of GnRHa instead of HCG in any case at risk of developing OHSS. PMID- 8006129 TI - Anthropometric indicators and response to gonadotrophin for ovulation induction. AB - A total of 111 women with no ultrasonographic findings of polycystic ovarian syndrome were observed between January 1989 and December 1991 in an in-vitro fertilization (IVF) programme. The treatment schedule involved ovulation induction after treatment with a gonadotrophin-releasing hormone (GnRH) agonist, using standard doses of human menopausal gonadotrophin (HMG) for 4 days, and further stepwise increments in dosage as required. Response to the treatment was defined as: (i) presence/absence of one or more follicles > or = 10 mm diameter after 4 days of treatment, and (ii) oocyte retrieval. Three indices of body mass were considered: weight (W) in kg/height (H)2 in metres (Quetelet's index), W/H1.5 (the National Health and Nutrition Examination Survey anthropometric index for women), W0.30/H (ponderal index). Surface area was computed as 0.0235 (H in cm0.422) (W in kg0.515). Women in the upper tertiles of the range of anthropometric indicators more frequently tended to present no follicle > or = 10 mm on day 7. Likewise, oocytes were retrieved less frequently in subjects in the higher tertile than in those in the lower. The odds ratio of a negative response both on day 7 and at the end of treatment increased with the tertiles of body mass indices or surface areas. This study suggests that response to ovulation induction treatment is inversely related to body mass index. PMID- 8006131 TI - Steroid antagonists and receptor-associated proteins. PMID- 8006132 TI - Contraception by the end of the 20th century. PMID- 8006130 TI - Multiple follicular development and ovarian steroidogenesis following subcutaneous administration of a highly purified urinary FSH preparation in pituitary desensitized women undergoing IVF: a multicentre European phase III study. AB - A multicentre, multinational study was carried out between November 1990 and February 1992 to assess the safety and efficacy of a new highly purified urinary human follicle stimulating hormone (FSH; Metrodin HP) which is practically devoid of luteinizing hormone (LH) activity. Metrodin HP was administered s.c. to stimulate multiple follicular development in women undergoing in-vitro fertilization (IVF) and embryo transfer. A total of 139 women were recruited from 10 participating centres. Of these, 135 underwent pituitary desensitization with a long gonadotrophin-releasing hormone (GnRH) agonist protocol and following determination of ovarian inactivity (mean +/- SD of 12.9 +/- 3.2 days), Metrodin HP s.c. stimulation was started; 122 patients were fully eligible for efficacy analysis and 118 of these (97%) received up to 10,000 IU human chorionic gonadotrophin (HCG) to induce final follicular maturation and timed oocyte recovery. Mean plasma LH concentrations at the beginning of Metrodin HP treatment were 1.6 +/- 0.8 mIU/ml and by the day of HCG administration were significantly (P < 0.001) reduced (1.2 +/- 0.8 mIU/ml). The mean plasma oestradiol and inhibin concentrations on the day of HCG were 6173 +/- 3567 pmol/l and 8.2 +/- 4.4 IU/ml respectively. There was a positive correlation (r = 0.49, P < 0.001) between individual oestradiol and inhibin concentrations on the day of HCG. In the 118 patients who received HCG, the mean number of oocytes recovered was 8.4 +/- 4.7 following stimulation with 36 +/- 10, 75 IU ampoules of Metrodin HP over 12.2 +/- 2.1 days.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8006134 TI - Computer-assisted measurement of hyperactivation in human spermatozoa: differences between European and American versions of the Hamilton-Thorn motility analyser. AB - Spermatozoa from healthy donors of proven fertility were analysed for percentage hyperactivation, mean curvilinear velocity (VCL), mean progressive velocity (VSL), amplitude of lateral head displacement (ALH) and percentage linearity (LIN) using two versions of the Hamilton-Thorn motility analyser (HTMA) running at different frame rates. The sort fraction criteria developed using a machine utilizing 30 Hz gave comparable figures for the percentage spermatozoa displaying motility patterns concomitant with hyperactivation when compared to that developed for a machine using a frame rate of 25 Hz. Statistically significant differences were observed when criteria developed using 30 Hz machines were transferred to those using 25 Hz. The frame rate dependency of VSL and VCL are thought to account for these differences; values for ALH and LIN were largely unaffected by frame rate. These results have implications for workers using the European version of the HTMA (at 25 Hz) with sort criteria, containing frame rate dependent variables, which have been developed by American colleagues using the machines of a higher frame rate. More appropriate sort criteria for workers using European (25 Hz) machines are suggested. PMID- 8006133 TI - The probability of a successful treatment of infertility by in-vitro fertilization. AB - The objective of this study was to define several estimates of the success rate of in-vitro fertilization and embryo transfer treatment in relation to treatment outcome. The data were collected in a retrospective study of 591 patients treated during 3 years in one Belgian university hospital. Several models used for evaluating the treatment of infertility were fitted to the data (logistic model, binomial model, double binomial model, exponential model, the Speirs model. The number of oocytes retrieved and the proportion of fertilized oocytes at the first attempt can be used as prognostic factors. According to these factors, the success rate after five attempts varies from 28 to 88%. PMID- 8006135 TI - Unilateral testicular obstruction: orchidectomy or reconstruction? AB - Unilateral testicular obstruction can cause infertility in man by reducing sperm output, or by stimulating antisperm antibody production. Amongst 125 subfertile men with unilateral blocks, the causes were defined as post-infective (n = 72), post-traumatic (n = 41) or congenital (n = 12) by surgical exploration. Of these, 50 had severe oligozoospermia or azoospermia, and another 30 had oligozoospermia; 67 had significantly raised serum antisperm antibody titres. The outflow tracts were reconstructed in 87 men, while in 24 the obstructed testis was removed and replaced with a prosthesis. Follow-up information is available in 104 men. Reconstruction produced significant improvement in sperm concentration in the ejaculate but little change in antisperm antibody titres. Orchidectomy lowered seminal plasma antibody titres and had no effect on sperm output. Orchidectomy plus prednisolone was most effective in terms of pregnancies produced in the female partners. Testicular biopsies showed that spermatogenesis was normal on the side of the block in 90% of cases, whereas it was impaired in the contralateral testis in 40% of men. Although sperm output can be improved by reconstruction, the stimulus to antibody production is more reliably eliminated by orchidectomy. Sperm concentration, antisperm antibody titres and bilateral testicular biopsy results should be taken into account before making a final therapeutic recommendation in men with unilateral testicular obstruction. PMID- 8006136 TI - Effect of platelet-activating factor on motility and acrosome reaction of human spermatozoa. AB - The effect of platelet-activating factor (PAF) on motility parameters and induction of the acrosome reaction in human spermatozoa was investigated in 36 unselected men with different degrees of initial sperm motility. The characteristics of sperm movement were assessed by computer-assisted sperm analysis (Hamilton-Thorn Motility Analyser) and the percentage of acrosome reacted spermatozoa was evaluated after 1 h incubation with PAF (10 nM) and staining with fluorescent peanut lectin. We found that short-term (4 h max) incubation with PAF significantly enhanced total and progressive sperm motility as well as acrosome reaction. An increase of sperm motility in response to PAF was present in 16 out of the 25 subjects studied (defined as responders) and was inversely correlated with basal motility. In the 11 samples (six responders and five non-responders) where the incubation with PAF was prolonged overnight, an increase of sperm motility was present in all the subjects studied. Similarly, an increase in numbers of acrosome reactions in response to 10 nM PAF was present in 20 out of the 26 subjects examined, and was inhibited by the PAF receptor antagonist L659 989. Our results indicate a possible physiological role for PAF in fertilization and suggest a potential use of PAF in in-vitro fertilization techniques in cases of reduced sperm motility. PMID- 8006137 TI - The effect of pentoxifylline on sperm movement characteristics and zona pellucida binding potential of teratozoospermic men. AB - This study investigates the effect of pentoxifylline on sperm movement and zona pellucida binding. Spermatozoa from nine teratozoospermic patients (10.2 +/- 6% normal forms) were included in the study. Test samples were diluted with a 4 nM solution of pentoxifylline, and control samples with Ham's F-10 culture medium only. Zona pellucida binding potential was measured under hemizona assay conditions (HZA). Sperm motility was evaluated at the start (0 h post-swim-up) and end (4 h) of the HZA, under test-tube conditions and under HZA conditions (50 microliters droplet under oil). Motility parameters tested included the curvilinear velocity (VCL), straight line velocity (VSL) and linearity (LIN). Compared to the controls, pentoxifylline-treated samples showed an immediate stimulation of sperm motility, under test-tube conditions, with a significant elevation of VCL at 0 h incubation (102.77 +/- 14.4 versus control value 84.60 +/ 10.6 microns/s; P = 0.005), which however was reversed after 4 h incubation (73.16 +/- 4.6 versus control value 85.47 +/- 12.8 microns/s; P < 0.005). A decline in sperm motility from 0 to 4 h incubation was noted for all the pentoxifylline-treated samples, under both test tube conditions (VCL: 102.77 +/- 14.4 versus 73.16 +/- 4.6 microns/s, P < 0.005; VSL: 27.2 +/- 10 versus 10.66 +/- 2.2 microns/s, P < 0.005; LIN: 23.65 +/- 7.1 versus 11.86 +/- 1.8%, P < 0.005) and HZA conditions (VCL: 100.04 +/- 13.1 versus 76.00 +/- 7 microns/s, P < 0.005; VSL: 26.40 +/- 8.7 versus 9.14 +/- 4.5 microns/s, P < 0.005; LIN: 26.2 +/- 12 versus 11.05 +/- 4.3%, P < 0.005).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8006138 TI - Ultrasound transmission gel in the vagina can impair sperm motility. AB - The effect of ultrasound transmission gel on sperm motility was assessed because of a few unsatisfactory post-coital tests, encountered after vaginal ultrasonography in otherwise normal couples. Swim-up samples of spermatozoa from donors and patients with asthenozoospermia were incubated in ultrasonic transmission gel at various concentrations. Sperm progressive motility and viability were checked. Donor sperm progressive motility declined from 90.9 +/- 2.5% (mean +/- SD) to 30.6 +/- 2.7% (P < or = 0.001) within 18 h at a gel concentration of only 10% (by volume). There were no progressive motile spermatozoa after incubation in 80% gel. In the swim-up fraction from asthenozoospermic patients, motility declined from 92.2 +/- 2.5% to 11.6 +/- 2.1% (P < or = 0.001) within 130 min at a gel concentration of 10% (by volume). Eosin staining for viability demonstrated that the loss of motility was mostly due to loss of viability. The use of ultrasound transmission gel should be avoided during follicular follow-up close to the date of expected ovulation in couples who practise dated natural intercourse or cervical insemination. Normal saline is an adequate substitute in this period with relatively large follicles. PMID- 8006139 TI - The use of chymotrypsin/galactose to treat spermatozoa bound with anti-sperm antibodies prior to intra-uterine insemination. AB - Anti-sperm antibodies in semen have been associated with a decrease in fertility potential. The question arises as to whether intra-uterine insemination (IUI) can improve pregnancy rates by merely allowing earlier capacitation and close timing to ovulation, or whether certain treatments of the spermatozoa add extra benefit. The study presented herein was designed to compare IUI using Percoll density separation with an albumin treatment versus chymotrypsin/galactose treatment. Sixteen patients were evaluated where IUI was randomized between both sperm treatments. Pregnancy rates/cycle were 25% (eight of 32) with chymotrypsin/galactose-treated spermatozoa compared to only 3% (one of 33) cycles with albumin-treated spermatozoa (P < 0.01). Since it has been reported that the proportions of spermatozoa showing immunobead binding for specific antibodies after chymotrypsin/galactose treatment remain unchanged, the exact mechanism for improvement is unknown; possibly chymotrypsin/galactose interferes with the function of the antibodies. PMID- 8006140 TI - A new test for the assessment of sperm-zona pellucida penetration: relationship with results of other sperm tests and fertilization in vitro. AB - The spermatozoa of some patients attending for in-vitro fertilization (IVF) fail to penetrate the zona pellucida in vitro. A test has been devised to identify these cases. It is based on the number of spermatozoa penetrating into the zona pellucida, which were counted after removing spermatozoa bound to the zona surface by vigorous aspiration of each oocyte through a narrow gauge (120 microns) glass pipette. The oocytes were collected from 197 patients undergoing IVF treatment with their own gametes; 79 with no oocytes fertilized and 118 with some oocytes fertilized. Sperm motility, morphology and DNA normality (acridine orange stain) were also measured. The relationships between sperm test results and IVF rate were examined by logistic regression. The proportions of penetrated zonae, normal sperm morphology and normal DNA were the most significant factors related to IVF rate in the whole group. Also, in patients with > or = 30 spermatozoa bound per zona pellucida or with normal sperm morphology > or = 30%, the proportion of penetrated zonae and normal DNA were most significant. Oocytes from 42 patients who had zero fertilization and low sperm-zona binding (average, 2.2 spermatozoa/zona pellucida) were re-incubated with normal donor spermatozoa: large numbers of spermatozoa bound (average, 88 spermatozoa/zona pellucida) and each zona was penetrated by at least one spermatozoon. In conclusion, the percentage of zonae penetrated was the variable most significantly correlated with IVF rate. Penetration of the zona was also strongly related to fertilization rates in patients without defects of sperm morphology and sperm-zona binding.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8006141 TI - Removal of the ovarian surface epithelium from the rabbit ovary--a cause of adhesions following a standard injury. AB - To assess the effect of the removal of ovarian surface epithelium on repair, a standard injury was induced in the ovaries of 10 rabbits. In one ovary the surface cells were denuded, and in the other they were left intact. The effect on adhesion formation was assessed at 12 days. Adhesions were assessed by visual inspection at laparotomy and histological examination of adhesion formation, including a stereological assessment of scar volume. On visual assessment the overall adhesion scores for the denuded ovaries were greater than for the intact ovaries. Histology showed the adhesions were attached only to the site of injury. The Fallopian tube was adherent to 35 and 4% of the denuded and intact ovarian segments respectively (P = 0.003). The scar volumes for each side were similar. After 12 days there was only partial re-epithelialization on the denuded ovaries. Electron microscopy confirmed the slow healing, with much of the surface still covered by a fibrinous-like exudate. The findings of this small study lend further weight to the importance of the surface epithelium in the control of adhesion formation. Standard surgical procedures may generate adhesions by the inadvertent denuding of surface epithelium from adjacent healthy tissues, possibly by the loss of plasminogen activator activity that is found in the mesothelium of the peritoneum. This study highlights the importance of controlling for inadvertent cell loss whilst investigating methods for adhesion prevention. PMID- 8006142 TI - Micro-assisted fertilization in patients who have failed subzonal insemination. AB - During the past 3 years we have used direct injection of spermatozoa into the cytoplasm of the oocyte (DISCO) in an attempt to procure conception in vitro where subzonal insemination (SUZI) has failed. Acknowledging the paucity of information about this invasive procedure in humans, it was clearly the only alternative for some patients. A total of 58 patients (cycles) who had had previously failed SUZI elected for this approach. Sibling oocytes, where possible, were used as a comparison between DISCO, SUZI, partial zona dissection (PZD) and microdrop in-vitro fertilization (IVF). Fertilization and embryo transfer was achieved by 66% (n = 38) of patients. Patients with embryos derived solely from DISCO (n = 19) produced four clinical pregnancies (21%), four patients had embryo transfer from SUZI embryos only with no pregnancies, and 15 had embryo transfer from a mixture of SUZI and DISCO embryos, with one dizygotic twin pregnancy from a combined SUZI and DISCO embryo transfer (7%). Twins, one male and one female, have been delivered, there has been one miscarriage and two pregnancies are ongoing. Of the 627 oocytes, 251 were used for DISCO and 71 (28%) were fertilized, 296 were used for SUZI and 29 (10%) were fertilized; 70 were used for PZD, two (3%) were fertilized, and none of the 10 undergoing microdrop IVF were fertilized. Of the 58 patients (cycles) 31% (n = 19) had fertilization with DISCO only, 8% (n = 4) with SUZI only, 28% (n = 15) with both SUZI and DISCO, while only one (2%) had fertilization with PZD.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8006143 TI - Monospermic polyploidy and atypical embryo morphology. AB - Monospermic cleavage-arrested human embryos were analysed by fluorescence in-situ hybridization using specific DNA probes for chromosomes X, Y and 18 simultaneously. Two groups of monospermic polyploid embryos could be distinguished: (i) embryos (n = 13) with only one large cell surrounded by smaller blastomere-sized extracellular fragments. These embryos were polyploid and frequently polyploid mosaic. (ii) Embryos developing from larger than normal oocytes were triploid or triploid mosaics (n = 4). Atypical morphology was not seen in eight other polyploid monospermic embryos. The atypical morphologies described here are quite rare, but are genetically uniform. Polyspermic embryos are the only other known example of a dual genetic-morphological abnormality. PMID- 8006144 TI - Human oocyte activation after intracytoplasmic sperm injection. AB - Oocyte activation is a series of events triggered by the fertilizing spermatozoon and necessary for the beginning of the embryonic development. Calcium plays a pivotal role in this process. Here we used confocal laser scanning microscopy to examine the changes in the concentration of intracellular free calcium ([Ca2+]i) in human oocytes after intracytoplasmic sperm injection (ICSI). The first considerable but short (< 2 min) increase in [Ca2+]i was detected immediately after the penetration of the microinjection needle into the ooplasm. This rise by itself did not provoke oocyte activation and was also obtained after the injection of medium without spermatozoa. After a lag period of 4-12 h, oocytes that were subsequently activated initiated a second period of [Ca2+]i changes. These changes were sperm-dependent and followed one of two alternative patterns, a non-oscillatory one and an oscillatory one. The non-oscillatory pattern resembled the changes described previously during parthenogenetic activation of mammalian oocytes. The oscillatory pattern was similar to the changes accompanying normal fertilization in different mammalian species. It is concluded that the initial [Ca2+]i rise provoked by the ICSI procedure is not responsible for oocyte activation, and that a release of a sperm factor(s) is required to initiate this process. PMID- 8006145 TI - Changes in morphology, sperm penetration and fertilization of ovulated hamster eggs induced by oviductal exposure. AB - In the human, mature eggs at the pre-ovulatory follicular stage placed into the oviduct via gamete intra-Fallopian transfer (GIFT) establish more implantations and pregnancies than do those for standard in-vitro fertilization and embryo transfer (IVF). Previous studies in the hamster have shown that mature follicular eggs are less readily penetrated by spermatozoa than oviductal eggs. This study examines whether ovulation or pre-fertilization exposure to the oviduct per se affects sperm penetration and fertilization of mature ova. Three types of eggs were used: pre-ovulatory, follicular [12 h post-human chorionic gonadotrophin (HCG), 1-1.5 h pre-ovulation], and ovulated (bursal and oviductal, both 15 +/- 0.5 h post-HCG). Bursal eggs were obtained by ligating the infundibulum on one or both sides of the tract. The morphological changes in eggs due to oviductal exposure were quantified using computerized image analysis. Cumulus-free follicular and bursal eggs were significantly less penetrated than oviductal eggs 1 h post-insemination (36, 39 and 62%, respectively). Cumulus-intact oviductal compared to bursal eggs, paired within females, were fertilized at a significantly higher rate (4 h post-insemination; 89 and 58%, respectively). Fresh oviductal and bursal eggs had equivalent cell diameters (79 microns) and zona thickness (15-15.8 microns), but oviductal compared with bursal eggs had larger zonae (119 and 116 microns, respectively) and perivitelline volumes (107 and 47 pl). Oviductal, but not bursal, zonae had the oviductal glycoprotein, oviductin, bound to them. We conclude that prefertilization oviductal exposure and not ovulation or time post-HCG alters the morphology and fertilizability of eggs. PMID- 8006146 TI - Mouse oocytes derived from in vitro grown primary ovarian follicles are fertile. AB - A model culture system has been developed whereby individual, primary ovarian mouse follicles can be grown in vitro to the Graafian stage in the normal physiological time course, and then ovulated in response to luteinizing hormone. We report here on the successful fertilization and subsequent embryo development of the oocytes from such follicles. This is the first time that oocytes from in vitro matured whole follicles have been fertilized and shown to produce viable offspring in host animals. The study demonstrates that the culture system mimics physiological conditions for normal follicle development. PMID- 8006147 TI - Optimal preparation of preimplantation embryo interphase nuclei for analysis by fluorescence in-situ hybridization. AB - A new method was developed to prepare and isolate interphase nuclei from murine preimplantation embryos for analysis by fluorescence in-situ hybridization. Embryos were washed with phosphate-buffered saline and disaggregated in a small drop of bidistilled water containing HCl and Tween 20. During the disaggregation procedure embryos were watched continuously with an inverted microscope. Embryonic nuclei were digested with pepsin to make them accessible for hybridization to the probes and to remove remnants of cytoplasm. Nuclear and probe DNA were denatured simultaneously and hybridization was done overnight, followed by immunocytochemical detection of the probes. Using this method we were able to perform successful in-situ hybridization on all preimplantation stages of the mouse embryo (pronuclei, 2-cell, 4-cell, morula and blastocyst). Probes for the X and Y chromosomes were applied for sex determination. From the results described in this paper we conclude that the preparation and isolation of interphase nuclei from murine embryos with acid and Tween 20 offers high reproducibility, good morphology of the cells and a high hybridization efficiency. PMID- 8006148 TI - The evolution and outcome of pregnancies from oocyte donation. AB - A total of 199 patients participated in the oocyte donation programme in 336 replacement cycles in whom 69 clinical pregnancies were achieved, of which 53 reached term and delivery. Data concerning the evolution and outcome of pregnancies were retrieved in 52 cases, which involved 39 women with ovarian failure and 18 with functional ovaries. The most frequent complications of pregnancy were uterine bleeding in the first trimester in 18 cases (34.6%), hypertension in 17 (32.7%) and intra-uterine growth retardation (IUGR: 11.5%). These complications were more prominent in twin pregnancies. The Caesarean section rate was 63.5% and a high percentage of elective sections (54.5%) was observed. Of singleton pregnancies, 54.6% had a birth weight of > 3000 g at full term (> 37 weeks), while 62.5% of twins weighed between 2000 and 3000 g. One intra-uterine death occurred, so that the perinatal mortality was 1.7% and one newborn was operated on for stenosis of the pulmonary artery, while the incidence of premature labour was low (1.9%). A comparison of complications between pregnancies associated with ovarian failure and with functional ovaries revealed a higher frequency of bleeding in the first trimester (38.2% and 27.8% respectively) and of hypertension (38.2% and 22.2% respectively) in those with ovarian failure, although the differences were not statistically significant. In conclusion, women who become pregnant after oocyte donation and especially those with ovarian failure should be considered as high-risk obstetric patients. PMID- 8006149 TI - Birth characteristics and perinatal outcome of babies conceived from cryopreserved embryos. AB - The objective of this retrospective study was to compare the birth characteristics and perinatal mortality of babies conceived from the use of cryopreserved embryos with those resulting from in-vitro fertilization (IVF) and fresh embryo transfer. A total of 232 consecutive births, one pregnancy termination and a total of 283 babies in the cryopreserved group were studied. The IVF data included 763 births, three terminations and 961 babies, based on a previous analysis. There was no difference in the incidence of twin (18 versus 19%) and triplet births (2 versus 3%) in the cryopreserved and IVF groups respectively. The mean gestational age and birthweight of singleton, twin and triplet births were not significantly different between the groups. No difference was found in the perinatal mortality rates. The incidence of major congenital malformations in the cryopreserved group (1%) was significantly lower than that in the IVF group (3%; P < 0.05). It is concluded that the birth characteristics of babies conceived from cryopreserved/thawed embryos are similar to those from fresh embryos. There are fewer congenital malformations in the cryopreserved group. PMID- 8006150 TI - Treatment of ectopic pregnancy: the new gynaecological dilemma. AB - Recent diagnostic advances have resulted in earlier and more consistent diagnosis of ectopic pregnancy. This may be responsible, in part, for the increasing incidence of the condition. Also, early diagnosis of ectopic pregnancies has prompted conservative surgical treatment, the use of medical therapy and even expectant management in selected cases. The present article analyses the following main controversial questions concerning the management of ectopic pregnancy: whether to treat or not, and how to apply expectant management; whether therapy should be conservative or radical; whether conservative management should be surgical or medical; whether surgical intervention should be laparotomic or laparoscopic; and whether medical therapy should be systemic or local. PMID- 8006151 TI - Relationship of initial chorionic sac diameter to abortion and abortus karyotype based on new growth curves for the 16th to 49th post-ovulation day. AB - In order to determine whether initial chorionic sac diameter is related to subsequent abortion, abortus karyotype, or birth weight and length, chorionic sac diameter was prospectively measured by transvaginal ultrasound in 700 singleton pregnancies before post-ovulation day 31, the latest day cardiac activity becomes detectable in normal pregnancy. Results were compared to values for the 10th to the 90th centiles, determined from 227 measurements of in-vitro fertilization and gamete intra-Fallopian transfer pregnancies. The abortion rate was 23.9% [95% confidence interval (CI) 19.2%, 28.6%] when initial chorionic sac diameter was below the 50th centile, compared to 6.9% (95% CI 4.9%, 9.4%) when equal to or above the 50th centile. Chorionic sac diameter was below the 50th centile in all anembryonic abortions and in 62% of embryonic abortions. Triploidy, trisomy 47 + 16, or trisomy 16 and the presence of satellite bodies on chromosome 22 were the only abortus karyotypes significantly associated with small chorionic sac diameter. Initial chorionic sac diameter was not associated with birth weight or length. We conclude that chorionic sac diameter is decreased in anembryonic and embryonic abortion and that normal pregnancy outcome may be expected in 90-95% of pregnancies in which initial chorionic sac diameter is equal to or above average. PMID- 8006152 TI - Effect of pentoxifylline on mouse embryos. PMID- 8006153 TI - Treatments of male infertility. PMID- 8006154 TI - Cerebral palsy hip deformities: is there a consensus? II. Botulinum toxin A: a clinical experiment. PMID- 8006155 TI - Quantitative analysis of hip dysplasia in cerebral palsy: a study of radiographs and 3-D reformatted images. AB - Cerebral palsy patients (31 hips) were evaluated using radiographic and three dimensional (3-D) images to quantify hip anatomy. The 3-D images overcome distortions caused by joint contractures. Changes were more pronounced in the non ambulators and characterized by shallow sockets with increased neck-shaft angles. These hips tended to subluxate in a posterior-superior direction and most had defects in the femoral heads. Ambulators had increased femoral anterversion but other hip parameters tended to improve with age. The 3-D measures of roof steepness and socket depth were found to correlate strongly with radiographic parameters of subluxation. PMID- 8006156 TI - Clinical benefit of reconstruction of dislocated or subluxated hip joints in patients with spastic cerebral palsy. AB - Sixty-four dislocated hip joints in 47 patients with spastic cerebral palsy were reconstructed surgically for pain or physical impairment. The procedure included a femoral and pelvic osteotomy, an anterior iliopsoas transfer, and further soft tissue surgery. The study was based on a research questionnaire (mean follow-up 6.8 years) and radiographs (3.0 years). Upon review of radiographs, it was discovered that three hips had redislocated and that 23 were insufficiently covered. Four complications (one deep infection, three femoral fractures) occurred. Pain was relieved fully in 28 of 37 patients and eased in 9 of 37. Weight-bearing improved sitting problems in 22 of 26 patients and enabled nine of 36 nonwalkers to take at least a few steps. PMID- 8006157 TI - Iliopsoas transfer in cerebral palsy: the long-term outcome. AB - Thirty-three patients with cerebral palsy had iliopsoas transfers as part of their surgery for hip instability. All had total-body involvement, spastic cerebral palsy and none could walk. At the time of surgery, eight hips were subluxated and 39 were dislocated or severely subluxated. Mean follow-up was 8 years in patients between 8-25 years old. Forty-five of the 47 hips were located. Thirty patients had an accompanying scoliosis, and, in 10 patients, the rib cage impinged on the pelvis. Hip flexion had decreased in most patients. Sitting ability had not improved in any patient, and had in fact deteriorated in 50%. PMID- 8006158 TI - Management of spasticity in cerebral palsy with botulinum-A toxin: report of a preliminary, randomized, double-blind trial. AB - In order to evaluate further the efficacy of local intramuscular injections of botulinum-A toxin (BAT-A) in the management of dynamic equinus deformity associated with cerebral palsy, a randomized, double-blind, placebo-controlled study was undertaken. When evaluated using our Physician Rating Scale, 83% (five of six) of patients receiving toxin showed improvement, versus 33% (two of six) receiving placebo. There were no major complications. BAT-A injections appear to be safe and effective in children, and merit further prospective study. PMID- 8006159 TI - Posterior occipitoatlantal hypermobility in Down syndrome: an analysis of 199 patients. AB - We endeavored to determine the prevalence of occipitoatlantal hypermobility in individuals with Down syndrome, to establish objective radiographic criteria for this entity, and to correlate this with neurologic abnormality. In a retrospective analysis, upper cervical spine radiographs of 210 patients with Down syndrome were compared with those of 102 normal individuals. Radiographs were evaluated using the Powers ratio. Patients identified with radiographic evidence of posterior occipitoatlantal hypermobility were then examined clinically and compared with a matched group of patients with Down syndrome and normal Powers ratios. Of the patients with Down syndrome, 8.5% had a Powers ratio of < 0.55, which was indicative of posterior occipitoatlantal hypermobility (POAH). Furthermore, 66% of those with an abnormal Powers ratio had positive neurologic findings upon physical exam, a finding that was statistically significant when compared to a matched group of patients with Down syndrome and normal Powers ratio. PMID- 8006160 TI - Syringomyelia and scoliosis: a review of twenty-five pediatric patients. AB - A retrospective review of 25 patients with scoliosis secondary to syringomyelia was conducted. All patients had large syrinxes, but only 10 patients had abnormal neurologic findings, suggesting that subtle neurologic findings in patients with scoliosis should not be underestimated and supporting liberal use of magnetic resonance imaging (MRI). The results of three approaches to the care of these patients were reviewed: passive observation, bracing, and spinal fusion. Curves progressed > or = 5 degrees in patients aged < 10 years who were observed, but in children aged > 10 years, curves progressed > or = 10 degrees. Curves responded well to bracing, but correction was not maintained out of brace for patients with progressive and/or severe curves. Good corrective was achieved safely during operation. PMID- 8006161 TI - Excision of herniated nucleus pulposus in children and adolescents. AB - Eighty-eight patients were treated at the Alfred I. duPont Institute for disc disease from 1940 to 1989. Forty-eight patients, with an average age of 16 years, underwent discectomy. Twenty-three patients were followed for an average of 6 years after initial presentation. Thirteen patients, with an average age of 15 years, and who had radiographic documentation of disc disease, were treated nonoperatively. Eight patients were followed for an average of 6.3 years. The results of discectomy were rated as excellent or good in 91% of the patients, and poor in 9% at follow-up. In the patients treated nonoperatively, the results were rated as excellent or good in 25%, and poor in 75%. Our 6 year follow-up study suggests that discectomy yields excellent to good long-term results in children and adolescents. PMID- 8006162 TI - Congenital kyphosis in myelomeningocele: results following operative and nonoperative treatment. AB - We reviewed the cases of 16 patients with myelomeningocele and congenital kyphosis. Ten patients underwent kyphectomy with wire fixation and spinal fusion for severe-curve progression and problems with decubiti ulcers. The average curve magnitude at presentation for these 10 patients was 87 degrees (range 47-146 degrees); at an average follow-up of 5 + 8 years (range 2 + 9 to 9 + 9 years) after surgery, it was 60 degrees (range 15-80 degrees). A stable fusion was achieved in nine patients, and all 10 had improved status of their skin at their last follow-up. Six patients were managed by nonoperative means such as modified wheelchairs and orthoses. The average curve magnitude at the presentation for this group was 70 degrees (range 42 degrees - 93 degrees); at an average follow up of 19 years (range 5 + 5 to 27 + 3 years), it was 106 degrees (range 65 degrees - 130 degrees). Two of these patients continue to have problems with skin breakdown. Kyphectomy enables patients to sit straighter and is the proper treatment for these patients. If operative treatment is prohibitive or denied for some reason, then suitable wheelchair modifications can enable these patients to function with reasonable comfort. PMID- 8006163 TI - Pathogenesis of idiopathic scoliosis: SEPs in chicken with experimentally induced scoliosis and in patients with idiopathic scoliosis. AB - We studied somatosensory evoked potentials (SEPs) in 20 chickens with experimentally induced scoliosis after pinealectomy and in 100 patients with idiopathic scoliosis. We also studied 20 chickens without scoliosis and 20 healthy youngsters. In the chickens, SEPs after leg stimulation was significantly delayed in the scoliosis group compared to the controls. In patients, the latency of cortical potential (N37) after stimulation of tibial nerve was longer in the scoliosis group than in the controls. Our findings in both experimental and clinical studies strongly support the hypothesis that idiopathic scoliosis results from dysfunction in the central nervous system. The type of SEPs abnormalities described in idiopathic scoliosis suggest a pathology from the midbrain to the cortex. PMID- 8006164 TI - Adolescent stress fractures of the sacrum: two case reports. AB - Two teenage female athletes had low back pain that limited athletic activity. Radiographic examination was negative. A stress fracture of the ala of the sacrum was identified on bone scan and computed tomography (CT) scan. The lesions healed with rest. This unusual lesion has not been reported previously in the pediatric literature, but is probably more common than its lack of documentation suggests. Careful observation and evaluation of athletic individuals will enable identification of this lesion. Rest should allow fracture healing, followed by return to sports participation. Stress fractures of the sacrum should be included in the differential diagnosis of adolescent low back pain. PMID- 8006165 TI - Bone growth following lengthening for congenital shortening of the lower limb. AB - Bone and limb growth velocity ratios were studied in patients undergoing lengthening for unilateral congenital shortening of the lower limb. In 15 patients before lengthening, the length ratio (LR) between the normal and short sides remained constant with age. Consequently, the growth velocity ratio (GVR) between the normal and short sides also remained constant and equal to the LR. In 20 children, no significant change in GVR was observed after lengthening was carried out at a mean age of 9.6 years. Our results suggest that final limb length remains reasonably predictable and that an acceptable discrepancy can be expected, especially following lengthening after age 9 years. PMID- 8006167 TI - Nerve palsy during femoral lengthening: MRI, electrical, and histologic findings in the central and peripheral nervous systems--a canine model. AB - Six dog's femurs were lengthened until complete peroneal palsy was present. Ten 24 days later MRIs of the spinal cords were normal. EMGs located lesions at the spinal foramina in five dogs and at the lumbar plexus in one. In all dogs nerve conduction below the lesions was normal and amplitudes were diminished. Muscle histology confirmed neurogenic atrophy. Nerve histology at the sites of the lesions showed myelin and axon changes, but there was no Wallerian degeneration at or distal to those sites. Thus, the nerve lesions were either a variant of Sunderland first degree injury or were developing into second degree. PMID- 8006166 TI - Dislocation and subluxation during femoral lengthening. AB - Femoral lengthening by callus distraction was performed on 26 femurs of 18 patients with various disorders between 1988 and 1992. Age at surgery ranged from 6 to 17 years (13 years on average). The amount of lengthening varied from 2 to 7.5 cm (mean 5 cm). Follow-up evaluation of femoral-head displacement was based on the change of center-edge (CE) angle. The hips were divided into two groups based on the preoperative CE angle; one group consisted of 14 hips with a CE angle > 20 degrees and the other group consisted of 12 hips with an angle of < or = 20 degrees. In the first group, none of the hips deteriorated; however, five of 12 hips in the second group did deteriorate. One hip developed complete dislocation and the other four showed a decrease in the CE angle. Four of five deteriorated hips had a history of congenital dislocation of the hip and the other had multiple epiphyseal dysplasia. In cases in which the CE angle is < or = 20 degrees preoperatively, bony procedures such as innominate osteotomy should precede femoral elongation. PMID- 8006168 TI - Pediatric pain patterns during Ilizarov treatment of limb length discrepancy and angular deformity. AB - The Ilizarov method of gradual incremental distraction of long-bone deformities has provided dramatic functional improvement in children, but its cost in terms of pain may be high. The intensity of pain experienced and its progression with time was measured prospectively in 23 patients (age 11-20 years) by the Adolescent and Pediatric Pain Tool (APPT) and the Hospital for Sick Children (HSC) Pain Scale at four test intervals. These instruments were composed of visual analogue scales, body diagrams, and word lists. Results indicated high levels of pain extending over several months, in sharp contrast to the general orthopedic pain experience. The prolongation of pain throughout the entire correction and consolidation processes must be recognized to ensure appropriate management, particularly in the outpatient setting. PMID- 8006169 TI - Percutaneous epiphyseodesis. AB - The records of 29 patients who underwent epiphyseodesis of 56 physes in which a percutaneous (minimal incision) technique was used were reviewed. Length of surgery averaged 36 min per physis. Growth arrest was achieved in every instance. There were no cases of unplanned angular growth, no deep infections, and no difficulties in regaining full joint motion were reported. Epiphyseodesis of the proximal tibial physis was performed on 16 patients without epiphyseodesis of the proximal fibula, yet symptoms attributable to fibular overgrowth were not reported. Some technical variations that have evolved in our procedure are described. PMID- 8006170 TI - Dennyson-Fulford subtalar arthrodesis. AB - Forty-six patients who had undergone Dennyson-Fulford subtalar arthrodesis for hindfoot valgus deformities secondary to various pathologies were reviewed both radiographically and clinically. Mean age at surgery was 7.67 years; mean follow up was 5.67 years. Evaluation showed 70% good, 20% fair, and 10% poor results. Pseudarthrosis rate was 6.4%, and was not necessarily related to undercorrection or progressive deformity. Screw sclerosis, which is common, is associated with pseudarthrosis, but not with hardware failure. Hardware problems can be anticipated with intraoperative radiographs, and penetration of the lateral calcaneal cortex up to 1.0 cm is well tolerated. PMID- 8006171 TI - Cause of toe-in gait after posteromedial release for congenital clubfoot. AB - Eighteen children with 24 congenital clubfeet were examined for their foot progression angle and radiographic angles before and after Turco's posteromedial release. The foot-progression angle was -12.9 degrees before surgery and 1.6 degrees after surgery. The ratio of correction of the foot-progression angle was 58%. Using multiple regression analysis, this ratio was mostly related to the ratio of correction of the anteroposterior talo-first metatarsal and lateral talocalcaneal angles. These results suggest that it is important in correction of toe-in gait of congenital clubfoot to correct adduction deformity of the forefoot and equinus deformity of the hindfoot. PMID- 8006172 TI - Clubfeet and tarsal coalition. AB - Tarsal coalition was noted in 18 cases of rigid equinovarus deformity. Sixteen cases were encountered at surgery and two at morbid dissection. There were 14 patients in the series; six had associated pathologic conditions that might have caused their clubfeet to be deemed "teratologic," whereas eight did not and were considered to have congenital clubfeet. Four patients in the series had bilateral coalitions. Preoperative radiographs demonstrated the coalition in only one case. A presurgical magnetic resonance image (MRI) clearly showed the coalition in another case. Nonoperative treatment was unsuccessful. Two patients with tibial dysplasia had ankle disarticulations. The remaining 16 feet required extensive soft-tissue releases, internal fixation, and coalition excision. The vast majority of cases showed cartilaginous subtalar coalition at the medial facet. The patients were followed for an average of 6 years, and two recurrences were noted. Remaining feet were painless and plantargrade, but were rather stiff. This anomaly may be more common than previously described. It is usually not suspected preoperatively and may likewise be difficult to recognize at surgery. A preoperative MRI scan may also be helpful. PMID- 8006173 TI - Digital radiography in pediatric orthopaedics: a prospective, controlled, and randomized trial. AB - A prospective, controlled, and randomized trial of digital radiography was conducted to evaluate its advantages in children. Matched pairs of radiographs of the feet were taken in 20 children, and pelvic radiographs were taken in another 20 children. Each pair comprised a digital and conventional film. Half of the digital films were made with a 50% radiation dose reduction. The films were scored for quality. Statistically significant advantages were seen for the digital radiographs as compared with the conventional technique. Visualization of soft tissue and bony detail was enhanced in both foot and pelvic radiographs. This was true even with a 50% dose reduction in many of the parameters scored. We conclude that digital radiography offers advantages over conventional radiography, and recommend its use. PMID- 8006174 TI - Pelvic reconstruction after bone-graft harvesting. AB - Numerous pathological conditions of the spine require treatment involving the use of bone grafts. The iliac crest is a readily available donor site, but removal of bone may leave a major defect. The technique of reconstruction of the pelvic defect using the rib excised at the time of thoracoabdominal exposure is described. PMID- 8006175 TI - A radiolucent spine frame: a modification of the Relton-Hall spine frame. AB - A radiolucent spine frame for obtaining intraoperative spine radiographs while performing surgery for scoliosis has been designed at the Alfred I. duPont Institute and is described here. This frame, constructed of strong radiolucent plastic compounds, is easy to use and maintain. PMID- 8006176 TI - Longitudinal tendon splitting: a simple technique. AB - Orthopaedic surgeons are frequently confronted with the problem of joint contractures and the need for tendon lengthening. We describe a simple reproducible technique for longitudinal splitting of a tendon. We use this method for Z-lengthenings and split tendon transfers and recommend its use to other surgeons. PMID- 8006177 TI - The interposition of extensor digitorum brevis in the resection of calcaneonavicular bars. AB - In this series of 19 resected calcaneonavicular bars for peroneal spastic flatfoot (mean follow-up 3.4 years), we demonstrate that interposition of extensor digitorum brevis led to asymptomatic mobile feet without evidence of recurrence of the bar in 90% of the patients; this compares well with 43% recurrence rates of bars with associated pain and stiffness when extensor digitorum brevis is not interposed. We therefore recommend this method for prevention of the bar and their symptoms. PMID- 8006178 TI - Congenital glenoid dysplasia: case report in two consecutive generations. AB - Congenital glenoid dysplasia is a rare congenital condition of the shoulder. We report the case of a 6-year-old girl that was referred to our institution for restricted motion of both shoulders. Radiological examination revealed bilateral glenoid dysplasia. At the time of the child's examination, her mother also complained of shoulder stiffness; radiographs of her shoulders were taken and revealed that she too had glenoid dysplasia. Congenital glenoid dysplasia results from failure of development of the inferior ossification center of the glenoid fossa. Shoulder stiffness is the primary resultant disability, although it is variable. Our case is notable because we identified the dysplasia in two successive generations of the same family, although the mother was unaware she had the condition. PMID- 8006179 TI - A comparison of Wisconsin instrumentation and Cotrel-Dubousset instrumentation. PMID- 8006180 TI - Ultrasonic characterization of myocardial photocoagulation lesion size in vivo during Nd:YAG laser irradiation. AB - Endocardial coagulation lesions were created using transcatheter continuous-wave Nd:YAG laser irradiation. Ultrasound monitoring of thermal lesion dimensions was performed using 7.5-MHz and 10-MHz transducers directly from the epicardial surface in short-axis configuration (group A) or through the chest wall (group B). A total of 33 lesions were created in 10 dogs at energy levels ranging from 300 J to 1000 J. Mean histological lesion width (HW) compared with ultrasonically determined mean width (UW) showed that the differences (mean +/- standard deviation) in group A (UW - HW) was = 1.14 +/- 0.8 mm, which was not statistically significantly different from zero. In group B, (UW - HW) = 2.04 mm +/- 0.7 mm (p < .05), which was statistically significantly different from zero. Mean histological depth (HD) differentially related to ultrasound mean depth (UD) for group A and B combined showed (UD - HD) = -0.19 mm +/- 0.46 mm, not statistically significantly different from zero. The frequency distribution for width in group A showed magnitude of UW-HW > 3 mm in 32% of cases. In group B magnitude of UW-HW > 3 mm in 15%, whereas ultrasound width was larger than histology in 75% of the cases. For depth, magnitude of UD-HD > 3 mm in 15% of cases. With further refinement of the technique, ultrasonic tissue characterization may become a useful adjunct to monitoring lesion dimensions during transcatheter laser photocoagulation. PMID- 8006181 TI - Evaluation of Doppler echocardiographic atrial pacing stress test in the detection of coronary artery disease. AB - Doppler echocardiographic atrial pacing stress tests were performed in 23 patients with coronary artery disease (CAD) and 35 normal subjects. It was found that the peak flow velocity (PFV) through the mitral valve decreased at 160 beats per minute (BPM) during pacing in the CAD group (P less than 0.01), but no significant variation was seen in the normal group. No differences between the two groups were observed in 1/3 filling fraction (1/3 FF), total diastolic filling period (DFP) and the ratio of early diastolic filling period (EDFP) to DFP before pacing. However, 1/3 FF and DFP decreased and EDFP/DFP increased immediately following rapid pacing in the CAD group but did not change in the normal group (P less than 0.05, 0.01, and 0.001 respectively). The peak flow velocity during atrial contraction (APFV), time velocity integral during atrial contraction (ATVI) and the ratio of ATVI to total TVI (ATVI/TTVI) increased immediately following pacing in the CAD group. Using two of three indices- ATVI/TTVI more than 0.35, ATVI increase and 1/3 FF decrease immediately following pacing--as diagnostic criteria for CAD, the sensitivity was 86% and the specificity was 77%. It may be concluded that the Doppler echocardiographic atrial pacing stress test is a feasible and reliable method for detecting CAD. PMID- 8006183 TI - Prediction of the neonatal crown-heel length from femur diaphysis length measurements. AB - The usefulness of the Rossavik growth model in predicting crown-heel length (CHL) was evaluated in 50 women with normal singleton pregnancies in a Dutch population. The femur diaphysis lengths (FDL) were predicted assuming growth cessation at 38, 39, 39.5, and 40 weeks, menstrual age (MA), and at birth using Rossavik growth models determined from two second-trimester FDL measurements. Predicted CHLs were then calculated from predicted FDLs using six different equations. Predicted CHLs were compared with the actual neonatal CHLs and the percent differences calculated. The growth potential realization index (GPRI) values were also determined. With all six equations, regression analysis revealed a significant relationship between the percent differences and birth ages for those infants delivering after 38 and 39 weeks, MA, respectively. The signs of the slopes of the regression lines were negative, indicating continued growth of these fetuses. With the Vintzileos equation, no evidence of continued growth was obtained after 39.5 weeks, MA. The systematic prediction error at this time point was 0.9%, whereas the random error was 3.3%. The mean GPRICHL was 99%, with a 95% range of 93% to 104%. These findings indicate that the CHL can be predicted with a high degree of accuracy in this Dutch population if the appropriate growth cessation age and FDL-CHL function are used. PMID- 8006182 TI - Amyloidosis of the thyroid gland: role of ultrasonography. AB - We studied the role of ultrasound assessment of the thyroid gland in detecting amyloid deposition in 9 patients confirmed to have renal amyloidosis because the thyroid gland is a readily accessible organ. Ultrasound examination of the thyroid gland showed a distinctive abnormal appearance in 7 patients. There was enlargement of one or both lobes of the thyroid, a high echogenicity approaching that of the surrounding connective tissue, and a very fine homogeneous echotexture similar to ground glass appearance. Four patients showed dilated follicles in the thyroid gland. The other two patients had normal ultrasound findings. Open wedge biopsy of the thyroid gland in 4 patients, (3 with abnormal ultrasound findings and 1 with normal ultrasound findings) showed amyloid deposits in the 3 patients with abnormal echo findings and no amyloid deposits in the 1 patient with normal findings. In 10 healthy individuals, 10 patients who were just initiated on maintenance hemodialysis and another 10 patients on dialysis for more than 1 year, the thyroid gland was of normal size and appearance in the ultrasound examination. We conclude that ultrasound examination by an experienced radiologist is a useful tool in the diagnosis of thyroid amyloidosis. PMID- 8006184 TI - Prediction of neonatal crown-heel length in normal singletons, twins, and triplets using individualized growth assessment. AB - In groups of normally growing singletons (20), twins (20), and triplets (13), predicted femur diaphysis length (FDL) values at birth were obtained using Rossavik growth models specified from second-trimester ultrasound studies of fetal growth. Six previously published functions were utilized to obtain predicted crown-heel length (CHL) values from predicted FDL values. These values were compared to the actual CHL values and the percent differences calculated. Based on their systematic (mean percent difference) and random (standard deviation of percent difference) prediction errors, the functions of Vintzileos (singletons), Hadlock (twins), and Brown (triplets) were found to give optimal results (no systematic error; random error: +/- 6%). Using predicted CHL values obtained with these optimal functions, growth potential realization index values for CHL (GPRICHL) were determined for singletons, twins, and triplets. In all three groups, the mean GPRICHL value was 100% with a range of approximately 95% to 105%. These results indicate that the CHL can be predicted from second trimester growth patterns and evaluated using individualized growth assessment methods. PMID- 8006185 TI - Ultrasonography of the thyroid gland in hospitalized, chronically ill geriatric patients: thyroid volume, its relationship to age and disease, and the prevalence of diffuse and nodular goiter. AB - Ultrasongraphy of the thyroid gland was performed in a screening study of 177 chronically ill, hospitalized geriatric patients older than 60 years of age, from an area with only moderate iodine deficiency. The normal reference ranges of thyroid volume for males (1.7 mL to 22.2 mL) and for females 2.4 mL to 20.9 mL) were similar. The thyroid volume decreased with age in the euthyroid group and was also smaller in euthyroid females in bad health. The prevalence of goiter and thyroid nodules were 7.9% and 11.3%, respectively. Thus, the decrease of the thyroid volume in this geriatric population is probably related to both old age and diseases of the aged. PMID- 8006186 TI - Maternal umbilicus: ultrasound window to the gravid uterus. AB - Transabdominal sonograms of 68 consecutive pregnant women were reviewed retrospectively. Images of fetal parts obtained through the umbilical window (UW) were compared with those obtained through the paraumbilical window (PUW) as to (1) thickness of tissue to amniotic cavity, (2) clarity of the part imaged, and (3) noise produced. The paraumbilical tissue thickness had a mean of 18 mm; the umbilical tissue thickness, a mean of 11 mm. In patients where the difference in thickness of their paraumbilical tissue and umbilical tissue was only 0 mm to 6 mm (group 1), the UW improved clarity in 10 of 34 (29%), reduced clarity in 3 of 34 (9%), and did not change clarity in 21 of 34 (62%). Improvement of images with use of the UW was not statistically significant. However, in the group of patients with the difference in tissue thickness between the paraumbilical and umbilical areas of > 6 mm (group 2), clarity was improved in 19 of 32 (60%), reduced in 2 of 32 (6%), and was unaltered in 11 of 32 (34%). In this group the image improvement with the UW was statistically significant. Images through the UW had relatively less noise. In group 1, noise was reduced in 12 of 35 (34%). The effect of the UW on noise reduction was more significant in group 2 (tissue thickness difference > 6 mm): 24 of 31 (77%) of cases. PMID- 8006187 TI - Nephrogenic adenoma in urethral diverticulum in a woman. PMID- 8006188 TI - Rhizomelic chondrodysplasia punctata: early recognition with antenatal ultrasonography. PMID- 8006189 TI - Amniotic band syndrome: serial ultrasonographic observations in the first trimester. PMID- 8006191 TI - Foreign body ingestion in a baby: sonographic localization. PMID- 8006190 TI - Unusual pattern of reversible renal hyperechogenicity associated with acute myoglobinuric renal failure. PMID- 8006192 TI - Analysis of pulmonary venous flow by Doppler echocardiography in patients with dilated cardiomyopathy. PMID- 8006193 TI - Sonographic detection of hydrolethalus syndrome. PMID- 8006194 TI - Clinical pharmacokinetics of lithium. PMID- 8006195 TI - Drug trials in children: ethical, legal, and practical issues. AB - Technical limitations, logistic challenges, and ethical constraints no longer provide excuses for not conducting well-designed studies of therapeutic agents in children. In fact, to not do so is difficult to defend ethically. Clinical trials in children are feasible and essential for safe and effective use of medications in children. The time is long past when drugs with therapeutic potential in children should be marketed with labeling for use only in adults. PMID- 8006196 TI - Epidemiologic evaluation of drug use in children. AB - To define and evaluate the attention devoted to drug use in children rather than just review existing reviews, the present attempt is to seek out the primary sources of information in the hope that this effort would not only yield more reliable data, but would also provide an opportunity for reconsidering methodological problems which are possibly even more important. An English language literature search for drug use in children from 1988 was conducted on two databases and a manual search was made of the literature, with a check of references quoted in main original articles, reviews and textbooks. The review was then organized in two main sections: an overall evaluation of the recent literature concerning drug use in children; the epidemiological profile of drug exposure as described cumulatively by the drug-utilization studies. A substantial lack of systematic attention to this area of drug epidemiology was found: drug use in the children is a 'hidden' reality in the literature; the wealth of methodologic developments that have taken place in the general field of drug use monitoring has scantly reached children. Children can be considered still "methodologic orphans" with respect to the transferable knowledge on the benefit/risk profile of therapies they receive. A network has to be developed to monitor clinical problems, including drug use, as part of an "audit" of the overall management of children. PMID- 8006197 TI - Teaching clinical pharmacology to non-native speakers of English: a study in a new university. PMID- 8006198 TI - Neonatal phenobarbital and phenytoin binding profiles. AB - Phenobarbital and phenytoin binding profiles were determined in 27 neonates. Binding of both drugs decreased compared with that in older subjects. In vitro binding of both agents correlated significantly with total protein and albumin concentrations. In vivo binding at 0.5 hours correlated significantly with birthweight and gestational age. Phenobarbital, but not phenytoin, binding decreased when three other therapeutic agents were concomitantly administered. Bilirubin concentrations, free fatty-acid concentrations, and pH values encountered in this population did not significantly influence binding. An in vitro binding profile accurately predicted in vivo free fractions (percent drug unbound) and plasma concentrations of both drugs. PMID- 8006199 TI - Disposition of clozapine and desmethylclozapine in schizophrenic patients. AB - The disposition of the atypical clozapine and its desmethyl metabolite were evaluated in fourteen male chronic patients. A single 100 mg dose of clozapine was administered and blood sampling performed over the following 72 hours. The mean (SD) oral clearance and half-life of clozapine were 55.4 (29.7) L/hr and 13.7 (9.9) hours, respectively. The mean (SD) AUC for clozapine and desmethylclozapine was 2389.9 (1406) and 751.1 (622.9) ng.hr/mL, respectively. The elimination of the metabolite is rate limited by its formation from cloza pine. A wide interpatient variability in clozapine and desmethylclozapine pharmacokinetics was observed. PMID- 8006200 TI - An atypical course of neuroleptic malignant syndrome. AB - Based on the discussion of NMS, certain conclusions may be reached in regard to this patient. In the psychiatric setting, agitation and confusion alone are not suggestive of NMS. However in this patient, the symptoms of agitation, the rapid development of EPS symptoms unresponsive to anticholinergic therapy, autonomic changes (tachycardia, diaphoresis, and incontinence), and elevated CPK, met most of the diagnostic criteria described in Table VI. However, this case may have described an atypical presentation of NMS because of the absence of temperature increases during the onset of symptoms and the 7-week hospitalization for NMS. The patient's later onset of temperature elevations was a result of an aspiration pneumonia. Pneumonia and renal failure significantly increased the morbidity and extended the course of the illness. As a result, the diagnosis and specific treatment of NMS were delayed because of atypical symptoms and complications. In this patient, treatment of NMS with bromocriptine did not start until 10 days into hospitalization. A delay in pharmacologic therapy in this patient may have contributed to persistence of symptoms. The patient showed signs of improvement on day 21 during combination bromocriptine, benztropine, and dantrolene therapy. Moreover, this case exemplifies the rigorous need for supportive therapy and adjunctive pharmacologic therapy for primary and secondary complications resulting from NMS. In conclusion, because of the wide range of risk factors and variations of NMS, a systematic approach to diagnosing and treating NMS is critical to a successful outcome. Discontinuation of antipsychotics, maintenance of supportive therapy aimed at preventing dehydration, hemodynamic, and electrolyte imbalances, and pharmacotherapy are essential in the treatment of NMS. PMID- 8006201 TI - A placebo-controlled evaluation of single, escalating doses of CL 284,846, a non benzodiazepine hypnotic. AB - This report describes the first evaluation in humans of CL 284,846, a non benzodiazepine compound with a preclinical profile indicative of sedative/hypnotic properties. Healthy, normal male volunteers were assigned randomly to receive single oral doses of 1, 5, 15, 30, or 60 mg of CL 284,846 or placebo on a double-blind basis. Observations were made over the subsequent 25 hours to determine the safety, pharmacokinetic profile, and psychometric effects of the test compound. CL 284,846 was well tolerated in the normal volunteers, causing no significant changes in vital signs, EEG, ECG, hematologic, or clinical chemistry laboratory parameters. Although few adverse events were noted at doses less than 60 mg, at the highest dose (60 mg), all volunteers reported transient neurologically related adverse events (e.g., impaired concentration, difficulty focusing, and impaired coordination), reflecting the central nervous system action of the compound. Although determination of hypnotic efficacy was not an objective in this Phase I study, daytime treatment with 60 mg of CL 284,846 was associated with greater reports of drowsiness and impaired performance on psychomotor tests. However, memory, as assessed by a word recall test, was not affected at any dose of the compound. Pharmacokinetic analyses revealed CL 284,846 to be absorbed and eliminated rapidly (Tmax = 0.9-1.5 hr, T 1/2 = 0.9-1.1 hr), with a dose-proportional AUC (area under cure). Plasma levels of CL 284,859, the primary desethylated metabolite of CL 284,846, were much lower in humans than in other species, indicating that the metabolism of CL 284,846 in humans may differ from that of rodents and dogs. Overall, CL 284,846 was well tolerated, and the authors recommend repeating dose safety and pharmacokinetic studies in healthy volunteers. PMID- 8006203 TI - Intonation and speech rate in dysarthric speech. AB - Ten dysarthric speakers of various etiologies, type, and severity were compared to age-matched and gender-matched nondysarthric speakers on 40 short sentences. These sentences were presented in both declarative and interrogative versions. Measures of (1) mean intonation difference (average difference in fundamental frequency between the last syllables of interrogative and declarative sentences) and (2) speech rate were obtained using the IBM Speech Viewer system. Analyses of variance were performed on the resulting measures with subject group, sentence type, and sentence sets as independent variables. Results indicate that (1) intonation values are significantly reduced in the dysarthric group as compared to those for the nondysarthric group; (2) rate varies as a function of subject group, sentence type, and sentence set. Moreover, intonation varies with severity of dysarthria, but not speech rate. These findings concur with the notion that dysarthria is a deficit in performance rather than in competence. The results are also discussed in reference to "breath-group" theory for intonation (Lieberman, 1967). PMID- 8006202 TI - Angiotensin-converting enzyme inhibition increases exercise tolerance and muscle blood flow in rats with peripheral arterial insufficiency. AB - To determine the effect of angiotensin-converting enzyme (ACE) inhibition on exercise tolerance and muscle blood flow (BF) to ischemic limbs, both femoral arteries of male Sprague-Dawley rats (approximately 325 g) were surgically stenosed. Rats were either active (treadmill run, 20 m/min (a) 15% grade, 5 d/wk for 3 wk) or sedentary (limited to cage activity), and assigned to one of three doses of zabicipril at 0.0 (zero), 0.3 (low), and 3.0 (high) mg.kg-1.d-1 administered via food intake (N = 14-15/group). After 3 weeks, the left carotid and caudal arteries were catheterized under anesthesia for BF measurement later in the day. Muscle BF was determined during exercise at two treadmill speeds (20 and 30 m/min) with 85Sr and 141Ce labeled microspheres to ensure a peak BF. Plasma ACE was inhibited 31%, 65% in the low- and high-dose sedentary rats and 75%, 74% in the low- and high-dose active animals, respectively (P < 0.001). Angiotensin-converting enzyme inhibition improved exercise tolerance by 3 weeks, at a low speed (20 m/min) in the sedentary groups (P < 0.025) and in a dose dependent manner at a higher speed (25 m/min) in the active groups (P < 0.001). Blood pressures and heart rates during running were not different among groups. However, total hindlimb BF, reduced to approximately 33% of normal by femoral stenosis, was increased by ACE inhibition and chronic activity in a dose dependent manner (P < 0.025). Blood flows to the plantar flexors were most improved (approximately 20-40%; to 124 mL.min-1 x 100 g-1) in the high-dose groups (P < 0.01). The higher run speed did not increase BF above the low speed. Training adaptation, indicated by an enhanced muscle mitochondrial content (P < 0.001), was similar for low- and high-dose active animals. Our results indicate that ACE inhibition improves BF to ischemic muscles and, together with chronic physical activity, improves exercise tolerance. The results from this study support those advocating ACE inhibition in managing appropriate patients with peripheral arterial insufficiency. PMID- 8006204 TI - Spouses of individuals with laryngeal cancer: caregiver strain and burden. AB - A major proportion of care for patients with laryngectomies is provided by their spouses. This study assessed caregiver strain and burden using two standardized measures. Questionnaires were completed by 75 spouses of individuals with laryngectomies. The correlates of perceived strain and burden, time since the diagnosis of cancer, the caregivers gender, the caregivers present health status, and the effects of current stressors were considerations in the analyses. The strain and burden of caregiving decreased as time from the diagnosis of cancer increased. Male caregivers reported less strain and burden than female caregivers. Subjects reported strain and burden independent of other current stressors in their lives. Implications for counseling and support groups for caregivers are discussed. PMID- 8006205 TI - An epidemiologic study of stuttering. AB - A questionnaire designed to assess the prevalence of stuttering and its relation with: (a) central nervous system risk factors; (b) associated disorders (allergies, migraine-type headache, developmental dyslexia history, smoking, and drug abuse), and (c) depression symptoms, was given to a general population sample of 1879 Spanish-speaking university students (mean age = 24.0). A prevalence of 2% of self-reported stuttering was found. Results indicated that the prevalence of minor brain injury or dysfunction, developmental dyslexia history, word-finding difficulties, and depressive symptoms was higher among the self-reported stutterers than among the nonstutterers. PMID- 8006206 TI - Age-related differences in speech variability among women. AB - The purpose of this study was to examine the differences in variability of several measures of the speech produced by two groups of women, one aged 20-35 years and one aged 75 years and over. The subjects read the first paragraph of the "Rainbow Passage," sustained vowels at three loudness levels, and repeated a carrier phrase in which a series of 18 syllables were embedded. Data were gathered on intraoral pressure (PIO), vocal intensity, speaking fundamental frequency (SFF), voice onset time (VOT), and phoneme duration. The F-max test and ANOVA statistics revealed that the older women exhibited greater within-subject variability than the younger women for PIO, SFF, VOT, and consonant duration. These factors required more precise temporal, respiratory, phonatory, or articulatory adjustments than did the vocal intensity tasks or vowel duration. The variability differences found in this study may reflect individual patterns of acoustic and physiologic change in the speech produced by older women. PMID- 8006207 TI - Sexual risk profiles of delinquent and homeless youths. AB - Relatively little is know about the sexual behaviors of high-risk adolescents, such as delinquent and homeless youths. Having secured data from medical examinations, this study provides sexual risk profiles for a sample of delinquent (N = 245) and homeless (N = 160) youths in San Francisco, California. The study found several indicators of high-risk behaviors, such as high levels of STDs, trading sex for money or drugs, and unprotected sexual relations with multiple partners. The study suggests that communities provide better sex education and medical services to high-risk adolescents through multi-service health clinics, public health clinics, and street outreach. PMID- 8006208 TI - Providing antenatal services in a primary health care system. AB - A study sample of 880 women attending the primary health care center in the Al Baha region of Saudi Arabia was interviewed on their attitudes towards antenatal care services in the primary care setting. Some 91.3% of the women expressed positive views about obtaining the antenatal care in these centers. The major factor influencing their choice was the geographic location of primary health centers which are near to their residence and therefore more convenient for them to patronize. Other factors were the easier access to staff in primary care centers, especially mid-wives and female doctors. There was a significant relationship of age, parity and education with their current antenatal and delivery practices. The women also recommended less than ten antenatal visits before delivery. These findings are relevant to any policy regarding maternity services in the country. PMID- 8006209 TI - Arthur Lewis Piper, M.D.: a medical missionary in the Belgian Congo. PMID- 8006210 TI - The risks of piloting with advancing age. PMID- 8006211 TI - Survey of El Paso physicians' breast and cervical cancer screening attitudes and practices. AB - One hundred and ninety-eight primary care physicians in El Paso, Texas, were surveyed for their practices and attitudes concerning breast and cervical cancer screening. The response rate was 83%. For women 40-49 years old, 77% of respondents stated that they ordered a screening mammogram at least every two years. For women 50-74 years old, 73% said they ordered an annual screening mammogram. For women 75 years and older, 61% stated they ordered an annual screening mammogram. For women 40 years or older, 89% of respondents said they performed annual or more frequent clinical breast examinations. Eighty-four percent of respondents stated they ordered a Pap smear every 1-3 years, both for pre- and post-menopausal women. The most common reasons given for not ordering or doing a breast or cervical screening exam were patient refusal, knowledge that other doctor performs exam, high price, inadequate insurance, patient not under regular care, do not see patient for gynecologic care, and patient being seen for different reason. Seventy percent of respondents do vaginal smears on women who have had a total hysterectomy for a benign condition, and 38% use a cytobrush for endocervical sampling. Respondents were generally more comfortable with their ability to do Pap smears (72% comfortable, 1% uncomfortable) than they were in performing clinical breast examinations (52% comfortable, 4% uncomfortable). Obstetricians and gynecologists were more likely than other physicians to do vaginal smears, use a cytobrush, and feel comfortable with their Pap smear technique. PMID- 8006212 TI - Moral and religious objections by hospitals to withholding and withdrawing life sustaining treatment. AB - A patient's right to decide about life-sustaining treatment may conflict with the policies of health care facilities that refuse on the basis or religious or moral convictions to honor certain decisions to forgo treatment. The New York State Task Force on Life and the Law examined the prevalence and nature of facility conscience objections to the refusal of life-sustaining treatment by conducting a survey of New York hospitals. Written questionnaires were distributed to hospitals in New York State. Fifty-eight percent of the New York State hospitals responded. Twenty-nine percent of the respondents indicated that their hospital would object on grounds of conscience either to withholding or to withdrawing life-sustaining treatment in at least one of the twelve hypothetical cases presented. Hospitals were more likely to have "no policy" for withdrawing than for withholding treatment. Only 10% of the hospitals that would object to decisions to forgo treatment on religious or moral grounds had stated the objections in writing. The patient's medical condition and the type of life sustaining treatment to be withdrawn or withheld are important factors in determining whether a hospital will object on grounds of conscience. The imminence of death appeared more decisive than the degree of debilitation or disability as a factor in the willingness to accept decisions to forgo life sustaining treatment. Hospitals should establish clear, written policies about their objections to forgoing treatment so that patients and their families can evaluate whether the facility meets their needs. PMID- 8006213 TI - Immunohistochemical detection of calcium/calmodulin-dependent protein kinase II in the spinal cord of the rat and monkey with special reference to the corticospinal tract. AB - Calcium/calmodulin-dependent protein kinase II is a prominent enzyme in the mammalian brain that phosphorylates a variety of substrate proteins. In the present study, monoclonal antibodies that specifically recognize either the alpha or the beta isoforms of this enzyme were used to determine the distribution of these isoforms within the rat and monkey spinal cord. In the rat, the corticospinal tract consists of two components: the dorsal corticospinal tract, which occupies the ventralmost aspect of the dorsal funiculus; and the ventral corticospinal tract, which occupies an area adjacent to the ventral median fissure. Both dorsal and ventral corticospinal tract fibers were strongly immunopositive for the alpha-antibody. Unilateral ablation of the sensorimotor cortex of the rat eliminated the alpha-immunoreactive staining in the contralateral dorsal corticospinal tract. The neuropil in the superficial laminae of the dorsal horn (Rexed's laminae I and II) was densely stained with the alpha antibody, whereas the neuropil in laminae IV-X was immunonegative. Dense alpha immunopositive neurons were also distributed in the head of the dorsal horn (laminae I-IV). In contrast to the strong alpha-immunoreactivity seen in the dorsal corticospinal tract fibers, only very weak beta-immunoreactivity was observed in this tract. Moderate beta-immunoreactive products were distributed homogenously throughout the neuropil of the gray matter, although the neuropil of the superficial laminae of the dorsal horn (laminae I and II) was stained more strongly than the other regions of the gray matter (laminae III-X). Neuronal components in all laminae were immunopositive for the beta-antibody. Thus, motoneurons in the ventral horn, which were immunonegative for the alpha antibody, were immunopositive for the beta-antibody. This selective distribution pattern of immunoreactivity of alpha- and beta-antibodies in the rat was also present in the monkey spinal cord, although the alpha-immunopositive corticospinal tract fibers in the monkey descended in the lateral funiculus as the lateral corticospinal tract instead of passing through the dorsal funiculus, as is the case in the rat. The differential distribution of immunoreactivity in the spinal cord suggests that these two isoforms of calcium/calmodulin-dependent protein kinase II may have different functional roles in the spinal cord. PMID- 8006214 TI - Development of lateral line organs in the axolotl. AB - Lateral line sensory receptors and their cranial nerves in axolotls arise from a dorsolateral series of placodes, including the octaval placode, that gives rise to the inner ear and the octaval nerve. Anterodorsal and anteroventral placodes occur rostral to the octaval placode and give rise to anterodorsal and anteroventral lateral line nerves and electroreceptors and mechanoreceptors of the snout, cheek, and lower jaw. Middle, supratemporal, and posterior placodes occur caudal to the octaval placode and give rise to similarly named lateral line nerves, electroreceptors and mechanoreceptors of the occipital region of the head, and trunk neuromasts. All placodes, except the posterior placode, elongate, forming sensory ridges, following the genesis of sensory ganglia. Primary mechanoreceptor primordia begin to form within the central zone of the sensory ridges at stage 36; primary electroreceptor primordia originate within the lateral zones of these ridges at stage 38. The first primary mechanoreceptors erupt during stage 37; all primary mechanoreceptors have erupted at hatching (stage 41). Primary electroreceptors begin to erupt at stage 43. Secondary mechanoreceptor primordia begin to form in 1-week-old larvae and erupt 1-2 weeks later. Secondary electroreceptor primordia also begin to form in 1-week-old larvae and continue until clusters of two to five electroreceptors are formed. The developmental stages thought to characterize lateral line placodes in the earliest gnathostomes suggest that this ancestral ontogeny has been truncated in modern amphibians, and ontogenetic mechanisms underlying placodal differentiation are suggested. PMID- 8006215 TI - Development of fungiform papillae, taste buds, and their innervation in the hamster. AB - Fungiform taste buds in mature hamsters are less subject to neurotrophic influences than those of other species. This study evaluates taste-bud neurotrophism during development in hamsters by examining the relation between growing nerves and differentiating fungiform papillae. Chorda tympani (CT) or lingual (trigeminal) nerve (LN) fibers were labelled with Lucifer Yellow as they grew into (CT fibers) or around (LN fibers) developing taste buds. Developing fungiform papillae and taste pores were counted with the aid of a topical tongue stain. The tongue forms on embryonic days (E) 10.5-11 and contains deeply placed CT and LN fibers but no papillae. By E12, the tongue epithelium develops scattered elevations. These "eminences" selectively become innervated by LN fibers that grow to the epithelium earlier and in larger numbers than CT fibers. Definitive fungiform papillae form rapidly during E13-14 and become heavily innervated by LN fibers. Intraepithelial CT fibers, rare at E13, invariably innervate fungiform papillae containing nascent taste buds at E14. During E14-15 (birth = E15-16), most papillae contain taste buds with pores, extensive perigemmal LN innervation, and extensive intragemmal CT innervation. At birth, numbers of fungiform papillae and taste pores are adultlike. The results show that fungiform eminences begin forming in the absence of innervation. The subsequent differentiation of definitive fungiform papillae and their innervation by LN fibers occur synchronously, prior to the differentiation of taste buds and their CT innervation. The hamster is precocious (e.g., compared to rat) in terms of LN development and the structural maturity of the anterior tongue at birth. PMID- 8006217 TI - Blood-eye barriers in the rat: correlation of ultrastructure with function. AB - The function of different vascular beds in the rat eye and brain was evaluated by measuring the transfer of a vascular tracer, 14C-alpha-amino-isobutyric acid, from blood to tissue. The density of vascular pores was measured in electron micrographs of perfusion-fixed, age-matched tissue to determine whether the differences in tracer transfer were paralleled by differences in ultrastructure. Tracer transfer in retina was approximately four times that in brain of the same animal. The transfer constant was not changed by the inclusion of cold alpha amino-isobutyric acid, showing that transport across retinal vessels is not saturable, and indicating that, as in brain, transport is due to passive diffusion. Ultrastructurally, retinal vessels have a higher density of interendothelial junctions and of endothelial vesicles, both of which suggest higher vascular permeability. However, pericytes, which contribute to a second line of defence in the blood-brain barrier, are approximately four times as numerous in retina as in brain, and we suggest that in the retina, they act to compensate for a more permeable endothelial barrier. Ciliary body vessels had a high transfer of tracer, probably as a consequence of the fenestrations in their walls. Iridial vessels had a relatively low transfer of tracer, similar to that in retina even though a proportion of the interendothelial junctions in iridial vessels had expanded junctional clefts suggestive of open paracellular channels. However, both iris and ciliary body may lose tracer to the anterior chamber fluid, leading us to underestimate the vascular permeability in these sites. PMID- 8006216 TI - The origin of serotoninergic afferents to the cat's cerebellar nuclei. AB - In the cat, serotoninergic (5HT) axons and terminals form a dense plexus that is present throughout the granule cell and Purkinje cell layers of the cerebellar cortex and all of the cerebellar nuclei. The intent of the present study was to identify the source of 5HT fibers in the cerebellar nuclei. The medial, interposed, and lateral cerebellar nuclei were selectively injected with either rhodamine or fluorescein-labeled latex microspheres that were retrogradely transported to brainstem neurons. Transverse sections of the brainstem were processed with a primary antibody to 5HT and secondary antibody tagged with either rhodamine or fluorescein. The location of neurons containing both serotonin-like immunoreactivity and retrogradely transported microspheres was plotted. All three of the cerebellar nuclei receive 5HT afferents from the nucleus locus coeruleus, the dorsal raphe nucleus, and the dorsal tegmental nucleus. In addition, the medial nucleus receives projections from the superior central nucleus, the nucleus raphe obscurus, the nucleus raphe magnus, and the periolivary reticular formation. The interposed nuclei receive additional projections from the nucleus raphe magnus, whereas the lateral nucleus receives additional projections from the superior central nucleus. In conclusion, the 5HT projections to the cerebellar nuclei do not appear to be collaterals of those projecting to the cortex (Kerr and Bishop, J Comp Neurol 304:502-515, 1991). These findings suggest that, although the cortex and nuclei are anatomically and physiologically related, they do not process all information in parallel. PMID- 8006218 TI - Cholinergic innervation of mouse forebrain structures. AB - Using choline acetyltransferase (ChAT) immunocytochemistry and acetylcholinesterase (AChE) histochemistry, we investigated regional and laminar differences in cholinergic innervation in the cerebral cortex, hippocampus, amygdala, and thalamus of mice. In mice, unlike rats, the patterns of ChAT immunostained and AChE-positive fibers are virtually identical in the cortex and are organized in a trilaminar pattern with cholinergic processes prominent in layers I and IV and within the lower portion of layer V and upper segment of layer VI. ChAT-immunoreactive cells were not seen in cortex. In the amygdala, the basolateral nucleus showed the highest density of cholinergic processes. In the hippocampus, a thin, dense band of ChAT-labeled processes was present in the inner segment of the molecular layer of the dentate gyrus and within the stratum oriens of CA1-3, adjacent to the basal aspect of pyramidal cells. Within the thalamus, anteroventral, mediodorsal (lateral portion), intralaminar, and reticular nuclei showed high densities of cholinergic processes. The results of this study provide the basis for examining the effects of transgenes and age on forebrain cholinergic systems. PMID- 8006219 TI - Electrical responses and synaptic connections of giant serotonin-immunoreactive neurons in crayfish olfactory and accessory lobes. AB - Five pairs of identified 5HT-IR cells in the deutocerebrum of the crayfish Cherax are known to have their synaptic endings in the accessory and olfactory lobes. Two of these cells, one on each side of the brain, are significantly larger than the others. Dye fills of these "giant" cells reveal each to be an interneuron with its branches confined to, but distributed throughout, the olfactory and accessory lobes on the side of the brain ipsilateral to its cell body and with no branches to the contralateral side. Intracellular recordings from the giant cells were made while stimulating the olfactory afferents and tracts within the brain in an attempt to discover the inputs and outputs to the cells. Electrical stimulation of chemoreceptor sensilla on the outer branch of the antennule does not excite the giant 5HT neurons. Focal extracellular electrical stimulation of the olfactory globular tract containing the axons of projection neurons from the olfactory and accessory lobes produces excitatory synaptic potentials and action potentials in the giant cells. Focal extracellular electrical stimulation of the deutocerebral commissure, the axons of which terminate in the glomeruli of the accessory lobes, also results in excitation of the giant cells. We conclude that the input to the giant cells is via axons in the deutocerebral commissure and collaterals from the projection neurons, ending in the glomeruli of the accessory lobes. The output of the giant cells is to the olfactory lobes, where it may serve to modulate olfactory signals. PMID- 8006220 TI - Synaptic output of physiologically identified spiny stellate neurons in cat visual cortex. AB - Spiny stellate neurons of area 17 of the cat's visual cortex were physiologically characterised and injected intracellularly with horseradish peroxidase. Six neurons from sublamina 4A were selected. Five had the S-type of simple receptive fields; one had a complex receptive field. Their axons formed boutons mainly in layers 3 and 4. An electron microscopic examination of 45 boutons showed that each bouton formed one asymmetric synapse on average. Spines were the most frequent synaptic target (74%); dendritic shafts formed the remainder (26%). On the basis of ultrastructural characteristics, 8% of the target dendrites were characterised as originating from smooth gamma-aminobutyrate-ergic (GABAergic) neurons. Thus the major output of spiny stellate neurons is to other spiny neurons, probably pyramidal neurons in layer 3 and spiny stellates in layer 4. PMID- 8006221 TI - Map of the synapses formed with the dendrites of spiny stellate neurons of cat visual cortex. AB - The synaptic input of six spiny stellate neurons in sublamina 4A of cat area 17 was assessed by electron microscopy. The neurons were physiologically characterized and filled with horseradish peroxidase in vivo. After processing the neurons were reconstructed at the light microscopic level using computer assisted methods and analyzed quantitatively. The extensive branching of the dendritic tree about 50 microns from the soma meant that the distal branches constituted five times the length of proximal dendrite. Proximal and distal portions of a single dendrite from each neuron were examined in series of ultrathin sections (1,456 sections) in the electron microscope. The majority (79%) of the 263 synapses examined were asymmetric; the remainder (21%) were symmetric. Symmetric synapses formed 35% of synapses sampled on proximal dendrites and were usually located on the shaft. They formed only 4% of synapses sampled on distal dendrites. Spines accounted for less than half of the total asymmetric synapses (45%); the remainder were on shafts. Symmetric synapses formed with four of 92 spines. Nine spines formed no synapses. Spiny stellate neurons in cat visual cortex appear to differ considerably from pyramidal neurons in having a significant asymmetric (excitatory) synaptic input to the dendritic shaft. PMID- 8006222 TI - Polyneuronal innervation of spiny stellate neurons in cat visual cortex. AB - Our hypothesis was that spiny stellate neurons in layer 4 of cat visual cortex receive polyneuronal innervation. We characterised the synapses of four likely sources of innervation by three simple criteria: the type of synapse, the target (spine, dendritic shaft), and the area of the presynaptic bouton. The layer 6 pyramids had the smallest boutons and formed asymmetric synapses mainly with the dendritic shaft. The thalamic afferents had the largest boutons and formed asymmetric synapses mainly with spines. The spiny stellates had medium-sized boutons and formed asymmetric synapses mainly with spines. We used these to make a "template" to match against the boutons forming synapses with the spiny stellate dendrite. Of the asymmetric synapses, 45% could have come from layer 6 pyramidal neurons, 28% from spiny stellate neurons, and 6% from thalamic afferents. The remaining 21% of asymmetric synapses could not be accounted for without assuming some additional selectivity of the presynaptic axons. Additional asymmetric synapses may come from a variety of sources, including other cortical neurons and subcortical nuclei such as the claustrum. Of the symmetric synapses, 84% could have been provided by clutch cells, which form large boutons. The remainder, formed by small boutons, probably come from other smooth neurons in layer 4, e.g., neurogliaform and bitufted neurons. Our analysis supports the hypothesis that the spiny stellate receives polyneuronal innervation, perhaps from all the sources of boutons in layer 4. Although layer 4 is the major recipient of thalamic afferents, our results show that they form only a few percent of the synapses of layer 4 spiny stellate neurons. PMID- 8006223 TI - Identification of the timing of S phase and the patterns of cell proliferation during hair cell regeneration in the chick cochlea. AB - Birds respond to hair cell loss by stimulating cell division in the otherwise mitotically quiescent sensory epithelium and by generating new hair cells. We examined cell proliferation during hair cell regeneration in chick basilar papilla by using 5-bromo-2'-deoxyuridine (BrdU). Chicks were noise exposed for 4 or 24 hours and injected with BrdU, and cochleae were immunohistochemically labeled to detect BrdU. Immunoreactivity after short-term postinjection survival identified when cells entered S phase. For both 4 and 24 hour exposures, cells in S phase were first detected in the sensory epithelium after an injection at 18 hours after the onset of exposure and were also present after injections at 24, 30, 36, 42, 48, 72, 96, 120, and 144 hours. The most cells in S (or G2) phase were detected at 42 and 72 hours for 24 hour exposures and at 48 hours for 4 hour exposures. Chicks that survived for long periods after injection had BrdU-labeled hair cells, indicating that precursor cells that divided in the presence of BrdU generated new hair cells. Moreover, labeled hair cells and supporting cells were grouped into discrete clusters, suggesting that cells within each cluster are clonally related. Support for this hypothesis was provided by experiments showing that the number of labeled cells increased when chicks survived for longer periods after a single BrdU injection. These findings suggest that progenitors within the sensory epithelium may undergo several rounds of division to generate the appropriate number of new hair cells and supporting cells. PMID- 8006224 TI - Effects of estrogen on the number of neurons expressing beta-endorphin in the medial basal hypothalamus of the female guinea pig. AB - The distribution pattern of immunoreactive beta-endorphin neurons was studied in female guinea pigs that were ovariectomized, and one week later were injected with 25 micrograms estradiol benzoate or oil. The animals (5 from each group) were perfused after 24 hours with 4% paraformaldehyde. The locations of beta endorphin cells and fibers were determined using avidin-biotin immunohistochemistry on free-floating vibratome sections. beta-endorphin immunoreactive fibers were distributed widely throughout specific regions of the rostral forebrain, similar to what has been described in other species. beta endorphin cell bodies were found in the arcuate nucleus and in adjacent ventrolateral areas throughout the rostrocaudal extent of the basal hypothalamus. Cells immunoreactive to beta-endorphin were also present in the caudal part of the ventromedial nucleus of the hypothalamus. The number of beta-endorphin neurons was quantified in anatomically matched sections through the rostral, medial and caudal basal hypothalamus of estradiol benzoate- and oil-treated guinea pigs. Analysis of variance revealed that the number of immunoreactive beta endorphin cells was significantly increased in all regions of the basal hypothalamus of estrogen-treated guinea pigs as compared to vehicle-treated animals (P < 0.01). These data indicate that in the guinea pig, the number of neurons expressing beta-endorphin is increased in the arcuate nucleus 24 hours after estrogen treatment. PMID- 8006225 TI - Morphological assessment of grafted rat and mouse cortical neurons: a light and electron microscopic study. AB - The morphology of cortical neurons grafted into (or near) the rat striatum was studied by means of intracellular Lucifer yellow injections in fixed slices. Rat donor syngeneic cortical tissue (from postnatal day 1 old rats; AO strain) as well as mouse donor xenogeneic cortical tissue (prenatal day 19; C3H/HE strain) were grafted as solid pieces into 8-12 week-old rats (AO strain). Recipients of mouse xenografts were immunosuppressed with a monoclonal antibody against the interleukin-2 receptor. After perfusion and sectioning of the graft-containing areas, individual slices were incubated in the DNA stain 4.6-diamidino-2 phenylindole (DAPI) to visualize the cell nuclei. Grafts could be easily identified by a surrounding rim of astrocytes which outline the border between grafted and host tissue. Grafted cortical neurons were intracellularly filled with Lucifer yellow, DAB-photoconverted, and further processed for light and electron microscopy. In general, no cortical lamination could be observed in the grafted rat and mouse cortical tissue, but neurons were loosely packed throughout the graft. Two major cell types could be identified in all grafts investigated so far. The majority resembled those described as spiny neurons (85%), which could be further classified into pyramid-like, spiny stellate-like or fusiform spiny neurons, with somata ranging between 15 and 25 microns in diameter. The remaining 15% resembled non-spiny neurons with either a multipolar basket-like or fusiform morphology. Dendrites of spiny and non-spiny neurons, which could extend to distances up to 400 microns, were never seen to cross the astrocytic border, but some main axon and axonal collaterals of spiny neurons were found to leave the graft. On the basis of light microscopic observations no difference was found between mouse and rat grafted cortical neurons. The results of this study show that grafted cortical neurons retain some of the characteristic features of neurons in the intact adult cerebral cortex, although there appears to be a greater preponderance of spiny neurons in grafted tissue. This may reflect an immaturity of the grafted tissue or a response to the striatal environment. PMID- 8006226 TI - Local circuit neurons immunoreactive for calretinin, calbindin D-28k or parvalbumin in monkey prefrontal cortex: distribution and morphology. AB - In the cerebral cortex, local circuit neurons provide critical inhibitory control over the activity of pyramidal neurons, the major class of excitatory efferent cortical cells. The calcium-binding proteins, calretinin, calbindin, and parvalbumin, are expressed in a variety of cortical local circuit neurons. However, in the primate prefrontal cortex, relatively little is known, especially with regard to calretinin, about the specific classes or distribution of local circuit neurons that contain these calcium-binding proteins. In this study, we used immunohistochemical techniques to characterize and compare the morphological features and distribution in macaque monkey prefrontal cortex of local circuit neurons that contain each of these calcium-binding proteins. On the basis of the axonal features of the labeled neurons, and correlations with previous Golgi studies, calretinin appeared to be present in double-bouquet neurons, calbindin in neurogliaform neurons and Martinotti cells, and parvalbumin in chandelier and wide arbor (basket) neurons. Calretinin was also found in other cell populations, such as a distinctive group of large neurons in the infragranular layers, but it was not possible to assign these neurons to a known cell class. In addition, although the animals studied were adults, immunoreactivity for both calretinin and calbindin was found in Cajal-Retzius neurons of layer I. Dual labeling studies confirmed that with the exception of the Cajal-Retzius neurons, each calcium-binding protein was expressed in separate populations of prefrontal cortical neurons. Comparisons of the laminar distributions of the labeled neurons also indicated that these calcium-binding proteins were segregated into discrete neuronal populations. Calretinin-positive neurons were present in greatest density in deep layer I and layer II, calbindin-immunoreactive cells were most dense in layers II-superficial III, and parvalbumin-containing neurons were present in greatest density in the middle cortical layers. In addition, the relative density of calretinin-labeled neurons was approximately twice that of the calbindin- and parvalbumin-positive neurons. However, within each group of labeled neurons, their laminar distribution and relative density did not differ substantially across regions of the prefrontal cortex. These findings demonstrate that calretinin, calbindin, and parvalbumin are markers of separate populations of local circuit neurons in monkey prefrontal cortex, and that they may be useful tools in unraveling the intrinsic inhibitory circuitry of the primate prefrontal cortex in but normal and disease states. PMID- 8006227 TI - Promoting dental research--a view from down under. PMID- 8006228 TI - Factors associated with hepatitis B vaccine response among dentists. AB - The objective of this study was to evaluate personal and immunization factors associated with serologic evidence of hepatitis B virus (HBV) vaccine response. A study was conducted using data from United States dentists participating from 1987 to 1991 in the Health Screening Program of the American Dental Association's annual session. This study included dentists (n = 507) who (1) received their most recent dose of HBV vaccine within the previous 10 months, (2) completed a core questionnaire, and (3) were tested for HBV markers (HBsAg, anti-HBs, and anti-HBc) and were found not to have evidence of past or present infection. Non responders were defined as dentists testing negative for all three markers (n = 100). Responders were defined as dentists having serological evidence of anti-HBs alone (n = 407). Logistic regression models were used to assess the relationship of vaccine response to the variables sex, age, number of vaccine doses, site of vaccination, type of vaccine, and history of hepatitis. Vaccine response was most strongly associated with sex, age, and number of doses. Factors unrelated to vaccine response included type of vaccine and history of hepatitis. Adherence to the recommended number of doses and early vaccination are critical to adequate protection against hepatitis B infection of dentists, who are often exposed to blood and other body fluids. PMID- 8006230 TI - Genotoxic and non-genotoxic effects of betel quid ingredients on oral mucosal fibroblasts in vitro. AB - To understand the role of betel quid (BQ) in the pathogenesis of oral submucous fibrosis (OSF) and oral cancer, we used DNA damage, cytotoxicity, and cell proliferation assays to study the pathobiological effects of aqueous extracts of three BQ constituents [betel nut (Areca catechu, BN), inflorescence of Piper betle (IPB), and lime], one BN alkaloid (arecoline), and one BN polyphenol [(+) catechin] on cultured oral mucosal fibroblasts. Extracts of BN and IPB induced DNA strand break formation in a dose-dependent manner. Extracts of BN and IPB, (+)-catechin, and arecoline decreased cell survival and proliferation in a dose dependent manner. However, aqueous extract of lime (50-800 micrograms/mL) increased cell proliferation by 20-40%. These results indicate that BQ contains not only genotoxic and cytotoxic agents, but also compounds which stimulate cell proliferation. These compounds may act synergistically in the pathogenesis of OSF and oral cancer in BQ chewers. In addition, five anti-oxidants [glutathione (GSH), cysteine, mannitol, catalase, and superoxide dismutase (SOD)] were tested for their protective effects against the cytotoxicity of BQ constituents. GSH (1.95 and 2.6 mmol/L) and cysteine (4 and 8 mmol/L) prevented the arecoline induced cytotoxicity. In contrast, mannitol, catalase, and SOD did not decrease the arecoline-induced cytotoxicity. These results indicate that thiol depletion, but not the attack of oxygen free radicals, could be the mechanism for arecoline cytotoxicity. GSH could also protect cells from the cytotoxicity of IPB extract. Increasing dietary intake of GSH-rich foods or dietary supplements of GSH may have chemopreventive potential to reduce BQ-associated oral lesions. PMID- 8006229 TI - Correlation between the BANA test and oral malodor parameters. AB - The purpose of the present investigation was to test the association between the BANA test (Perioscan, Oral-B), and oral malodor parameters. The subject population consisted of 52 Israeli adults, 43 of whom complained of oral malodor. Oral malodor measurements consisted of peak and steady-state volatile sulphide measurement by a portable sulphide monitor (Interscan Corp., model 1170), as well as organoleptic measurements of malodor from whole mouth, tongue, and saliva. Samples for the BANA test were obtained from four loci (shallow pocket, deep pocket, tongue dorsum, saliva); results were scored as negative (0), weak (1), or strong (2). BANA scores were significantly associated with odor-judge ratings, with the highest association obtained when BANA saliva scores and odor-judge saliva assessment were compared (r = 0.500; p < 0.001). BANA tests from the different loci were not significantly associated with sulphide monitor levels. Stepwise multiple-regression analysis of odor-judge measurements in terms of sulphide levels and average BANA scores showed that both log peak sulphide levels as well as BANA scores were significantly factored into the equations, yielding, in all cases, highly significant correlations (multiple r = 0.57, 0.50, and 0.59, respectively, with significance levels of 0.0001, 0.001, and < 0.0001, for whole mouth, tongue, and saliva malodor, respectively). The results suggest that the BANA scores are associated with a component of oral malodor which is independent of volatile sulphide measurements and suggest its use as an adjunct test to volatile sulphide measurement. PMID- 8006231 TI - Eugenol triggers different pathobiological effects on human oral mucosal fibroblasts. AB - Pathobiological effects of eugenol (4-allyl-2-methoxyphenol), a major constituent of betel quid (BQ), were studied on oral mucosal fibroblasts. At a concentration higher than 3 mmol/L, eugenol was cytotoxic to oral mucosal fibroblasts in a concentration- and time-dependent manner. Cell death was associated with intracellular depletion of glutathione (GSH). Most of the GSH was depleted prior to the onset of cell death. At concentrations of 3 mmol/L and 4 mmol/L, eugenol depleted about 45% and 77% of GSH after one-hour incubation. In addition, eugenol decreased cellular ATP level in a concentration- and time-dependent manner. Eugenol also inhibited lipid peroxidation. Inhibition of lipid peroxidation was partially explained by its dose-dependent inhibition of xanthine oxidase activity. The IC50 of eugenol on xanthine oxidase activity was about 0.3 mmol/L. No DNA strand break activity for eugenol was found at concentrations between 0.5 and 3 mmol/L. Taken together, frequent exposure of oral mucosa to a high concentration of eugenol during the chewing of BQ might be involved in the pathogenesis of oral submucous fibrosis and oral cancer via its cytotoxicity. In contrast, eugenol at a concentration less than 1 mmol/L might protect cells from the genetic attack of reactive oxygen species via inhibition of xanthine oxidase activity and lipid peroxidation. PMID- 8006232 TI - Difference in capacity between macrophages and dendritic cells from rat incisor pulp to provide accessory signals to concanavalin-A-stimulated T-lymphocytes. AB - The present study compared the ability of dendritic cells and macrophages derived from the dental pulp to provide accessory signals to Concanavalin A (Con A) stimulated T-lymphocytes. Pulpal cells from maxillary and mandibular rat incisors were enzymatically released with collagenase. T-lymphocytes were isolated from rat cervical lymph nodes. In initial experiments, suspensions of unseparated pulpal cells were found to provide co-stimulatory help to Con-A-treated T lymphocytes. The proliferation rate correlated well with the number of cells in the pulp suspension and followed a time course characteristic of a Con-A-driven proliferation of T-lymphocytes. Depletion of class II molecule-expressing cells from the unpurified suspension of pulpal cells resulted in lost ability to provide accessory signals to Con-A-stimulated T-lymphocytes. In contrast, removal of ED2-positive cells, i.e., macrophages, did not affect the ability of the suspension to give this assistance. Partially purified class II molecule expressing cells enhanced the proliferative response, while addition of enriched macrophages did not. It was concluded that cells in the normal dental pulp with the characteristics of dendritic cells have the capacity to provide help to Con-A stimulated T-lymphocytes, while cells with the macrophage phenotype lack this ability. PMID- 8006233 TI - Bone cell expression on titanium surfaces is altered by sterilization treatments. AB - Phenotypic responses of rat calvarial osteoblast-like cells (RCOB) were evaluated on commercially pure titanium (cpTi) surfaces when cultured at high density (5100 cells/mm2). These surfaces were prepared to three different clinically relevant surface preparations (1-micron, 600-grit, and 50-microns-grit sand-blast), followed by sterilization with either ultraviolet light, ethylene oxide, argon plasma-cleaning, or routine clinical autoclaving. Osteocalcin and alkaline phosphatase, but not collagen expression, were significantly affected by surface roughness when these surfaces were altered by argon plasma-cleaning. In general, plasma-cleaned cpTi surfaces demonstrated an inverse relationship between surface roughness and phenotypic markers for a bone-like response. On a per-cell basis, levels of the bone-specific protein, osteocalcin, and the enzymatic activity of alkaline phosphatase were highest on the smooth 1-micron polished surface and lowest on the roughest surfaces for the plasma-cleaned cpTi. Detectable bone cell expression can be altered by clinically relevant surfaces prepared by standard dental implant preparation techniques. PMID- 8006234 TI - Structure-property relations and crack resistance at the bovine dentin-enamel junction. AB - The present report is a study of the fracture behavior of the dentin-enamel complex, involving enamel, dentin, and the dentin-enamel junction (DEJ), that combines experimental design, computational finite element analysis, and fractography. Seven chevron-notched short-bar bovine DEJ specimens were utilized in this study. The general plane of the DEJ was approximately perpendicular to the fracture plane. All specimens were stored at 37 degrees C and 100% relative humidity for 24 h prior to being tested. A fracture test set-up was designed for application of tensile load on the DEJ specimens to initiate a crack at the vertex of the chevron in the enamel, across the DEJ zone and into the bulk dentin. During fracture testing, a water chamber was used to avoid dehydration of the specimen. The results showed that the lower boundary value of the fracture toughness of the DEJ perpendicular to its own plane was 3.38 +/- 0.40 MN/m1.5 and 988.42 +/- 231.39 J/m2, in terms of KIC and GKC, respectively. In addition, there was an extensive plastic deformation (83 +/- 12%) collateral to the fracture process at the DEJ zone. The fractography revealed that the deviation of the crak path involved an area which was approximately 50-100 microns deep. The parallel oriented coarse collagen bundles with diameters of 1-5 microns at the DEJ zone may play a significant role in resisting the enamel crack. This reflects the fact, that in the intact tooth, the multiple full thickness cracks commonly found in enamel do not typically cause total failure of the tooth by crack extension into the dentin. PMID- 8006235 TI - SEM evaluation of the resin-dentin interface with proprietary bonding agents in human subjects. AB - Laboratory studies on dentin bonding do not replicate physiological reality. This study examined with SEM the attachment produced in vivo under clinical conditions. Forty-four cavities were prepared in buccal/lingual surfaces of 16 premolar teeth scheduled for extraction and assigned randomly for treatment with: All-Bond 2 (Bisco) (A) with and (B) without dentin etch, (C) Scotchbond 2 (3M), (D) Scotchbond Multi-Purpose (3M), and (E) controls, using Enamel Bond (Kulzer) with dentin etch. After atraumatic extraction, restorations were split transversely by freeze-fracture and acid-treated. SEM examination of A revealed significant areas of gap-free attachment, with evidence of an acid-resistant hybrid layer (5-8 microns), often with resin tags of various lengths. Resin reinforced collagen fibers were seen. Gap formation was coincident with lack of bonding resin layer over primed dentin. Attachment with B was less effective; a hybrid layer was infrequently seen and few resin tags. Pooled bonding resin at internal line angles appeared to favor an effective bond. Treatment C resulted in large areas of detachment, leaving an adherent primed dentin layer with short resin tags. Treatment D revealed significant areas of gap-free attachment and evidence of a hybrid layer. Controls (E) showed total bond failure. Attachment with A and D was secure, restorations remaining in situ even after freeze fracture. This study confirmed that brief acid pre-treatment of dentin, allowing diffusion of resin-dentin primers, appeared conductive to development of an effective bond in vivo, similar to that reported in vitro. PMID- 8006237 TI - Within-subject comparisons of implant-supported mandibular prostheses: psychometric evaluation. AB - In a within-subject cross-over clinical trial, psychometric and functional measurements were taken while 15 completely edentulous subjects wore mandibular fixed prostheses and long-bar removable implant-supported prostheses. In this paper, the results of a psychometric assessment are presented. Eight subjects first received the fixed bridge and seven the removable type. After having worn a prosthesis for a minimum of two months, subjects responded to psychometric scales that measured their perceptions of various factors associated with prostheses. They also chewed test foods while masticatory activity was recorded. The prostheses were then changed and the procedures repeated. At the end of the study, patients were asked to choose the prosthesis that they wished to keep. Patients assigned significantly higher scores, on visual analogue scales, to both types of implant-supported prostheses than to their original conventional prostheses for all factors tested, including general satisfaction. However, no statistically significant differences between the two implant-supported prostheses were detected except for the difficulty of chewing carrot, apple, and sausage. For these foods, the fixed prostheses were rated higher. Subjects' responses to category scales were consistent with their responses to the visual analogue scales. These results suggest that, although patients find the fixed bridge to be significantly better for chewing harder foods, there is no difference in their general satisfaction with the two types of prostheses. PMID- 8006236 TI - Self-etching dentin primers containing phenyl-P. AB - The dentin bonding efficacies of two commercial dentin bonding systems and experimental self-etching dentin primers composed of methacryloxyethyl hydrogen phenyl phosphate (Phenyl-P) and either hydroxyethyl methacrylate (HEMA) or glyceryl methacrylate (GM,2,3-dihydroxypropyl methacrylate) were examined. The wall-to-wall polymerization contraction gap width of a commercial light-activated resin composite in a cylindrical dentin cavity and the tensile bond strength to a flat dentin surface were measured. Changes in dentin hardness were determined by Micro Vickers Hardness measurement, and an SEM observation was performed after priming. Formation of a contraction gap was completely prevented by the application of Phenyl-P diluted in HEMA or GM solution combined with a commercial dentin bonding agent, although gap formation was evident in nearly half of the specimens with both commercial dentin bonding systems. The mean tensile bond strengths of the tested groups varied from 16.3 to 20.7 MPa, and there were no significant differences between groups. Based on the measurement of Micro Vickers Hardness and SEM observation after priming, a slight reduction in dentin hardness was observed. However, this reduction in dentin hardness due to self-etching priming did not significantly correlate with either contraction gap width or tensile bond strength. PMID- 8006239 TI - Direction of a bite force determines the pattern of activity in jaw-closing muscles. AB - Human individuals were hypothesized to use the same pattern of jaw muscle activity to produce the same bite force. To test this hypothesis, we used a 2-mm thick force transducer to monitor the magnitude and direction of a bite force between a single pair of occluding first molars. Five subjects performed standardized bite force tasks. Six different magnitudes were tested, each in five directions. The surface electromyographic (EMG) activity in the left and right masseter and temporalis muscles was recorded, integrated, and normalized. Ratios of the EMG activity of paired muscles (e.g., the ratio of working temporalis and working masseter) were calculated for each bite force task. Each ratio was roughly constant for each direction of bite force, regardless of its magnitude. In contrast, when the magnitude of bite force was the same but the directions were different, the ratio was not constant. We conclude that the direction of a bite force, not its magnitude, determines the pattern of activity of jaw-closing muscles. The shared patterns of muscle activation may be the result of a subconscious optimization of jaw muscle forces to improve efficiency. PMID- 8006238 TI - Within-subject comparisons of implant-supported mandibular prostheses: choice of prosthesis. AB - Although previous studies have demonstrated that implant-supported prostheses are more satisfactory and efficient for edentulous patients than are conventional prostheses, until now no investigation has directly compared different types of implant-supported prostheses. We carried out a within-subject cross-over clinical trial with fixed and long-bar removable implant-supported mandibular prostheses. Fifteen subjects were randomly divided into two groups. One group received the fixed prosthesis first, while the other first received the removable. After a two month adaptation period, psychometric measurements of various aspects of the prostheses and physiological tests of masticatory efficiency were carried out. The prostheses were then changed, and the procedures repeated. At the end of the study, subjects chose the prosthesis they wished to keep. In this paper, we report on the data gathered at this last appointment. Eight subjects chose the fixed (F group), and seven chose the removable (R group). Both groups rated stability and ability to chew with the fixed as significantly better than with the removable. However, the R group rated ease of cleaning as the most important factor governing their decision, followed by esthetics and stability. The F group considered stability to be the most important factor in their decision, followed by chewing ability and ability to clean. There was a tendency for the removable to be chosen by older subjects (+50 years). These results suggest that patients choose fixed or removable implant-supported prostheses for specific reasons, and that patient attitudes should be considered when the design of a prosthesis is being planned for an individual patient. PMID- 8006240 TI - Rate modulation of jaw-elevator motor units as revealed from the low-frequency power spectrum of the surface electromyogram in myogenous CMD patients. AB - The firing pattern of the motor units (MUs) in jaw-elevator muscles was studied within a wide range of isometric contraction levels by means of changes in the frequency and broadness of the primary peak in the low-frequency (5-40 Hz) power spectral density function of the surface EMG. EMG was recorded from both masseter and anterior temporal muscles in 11 myogenous CMD patients as well as in 11 gender- and age-matched controls who clenched in intercuspal occlusion under the control of visual feedback at various levels (0.5-67% MVC for the various muscles studied). The EMG was digitized for 12 periods of 1.6 s per condition; the power spectrum was averaged and smoothed for the various clenching levels. Linear regression analysis showed that the positive slope in the peak frequency (PF)/% MVC relationship, a measure of rate modulation of the MUs, did not differ significantly between patients and controls. At a low clenching level, PF was smaller (p < 0.01) for the anterior temporal muscles of the patients, suggesting lower firing rates for a wide range of clenching levels of the patients because of a similar rate modulation for patients and controls. Furthermore, the variance in the slope values was larger (p < 0.05) for the masseteric muscles of the patients, which may be explained by more heterogeneity of the masseteric rate modulation in the patient group. The broadness of the primary peak was smallest at a low clenching level (p < 0.001) for the anterior temporal muscles of the patients, suggesting a more uniform firing rate or more synchronization between MUs. PMID- 8006241 TI - Are diagnostic criteria, time of episode and occupational impairment important determinants of the female:male ratio for major depression? AB - This study addresses whether the female preponderance in the 1-year prevalence of major depressive disorder is associated with differences in reporting symptoms or underreporting remote episodes, or the inclusion of work impairment in the case definition. In a sample of 1870 professionals and managers, we find (1) a more restrictive cut-off point for women does not eliminate the differential; (2) males and females equally underreport symptoms for remote episodes; and (3) adding impairment to the case definition marginally affects the F:M ratio. Thus, the large F:M prevalence ratio is not an artifact of ascertainment method, case definition, or differential recall. PMID- 8006242 TI - Normal urinary free cortisol and postdexamethasone cortisol in social phobia: comparison to normal volunteers. AB - In primates, social stress is associated with activation of the hypothalamic pituitary-adrenal (HPA) axis. Social phobia is a common, often disabling, form of pathological anxiety characterized by marked distress in situations involving possible scrutiny or evaluation. Little is known about HPA function in patients with social phobia. We examined 24-hour excretion of urinary free cortisol (UFC) in 54 patients with social phobia and post-dexamethasone cortisol levels in 64 patients with social phobia and found no evidence of HPA-axis overactivity compared to normal controls, despite pathological levels of anxiety. PMID- 8006243 TI - Response patterns of depressed outpatients with and without melancholia: a double blind, placebo-controlled trial of fluoxetine versus placebo. AB - Fluoxetine (20 mg/day) and placebo were compared in 89 outpatient men and women with major depression with (n = 52) or without (n = 37) DSM-III-R melancholia in an 8-week double-blind study to determine predictors of treatment response. Fluoxetine was statistically superior to placebo both within the melancholic subtype and in the total patient group (all measures). Response rate and mean decrease in 17-item Hamilton Depression Rating Scale total score approached statistical significance in favor of fluoxetine-treated melancholic patients compared with fluoxetine-treated non-melancholic patients. There were no statistically significant differences between fluoxetine-treated and placebo treated non-melancholic patients. Results support DSM-III-R melancholia as a predictor of antidepressant response. PMID- 8006244 TI - Adolescent bipolar disorder: a nine-year experience. AB - The clinical records of 53 adolescent inpatients diagnosed with bipolar disorder were re-evaluated to examine their profiles and differential diagnoses. Seventy two percent satisfied DSM-III-R Bipolar Disorder criteria and most presented with manic or mixed mood symptoms. Half were psychotic. Non-affective psychosis, unipolar depression, organic syndromes and disruptive behavioral disorders complicated the differential diagnoses, particularly among younger boys. The well documented bipolars were characterized by affective symptoms prior to the first admission and shorter hospitalizations than the remaining subjects. A recent trend towards overdiagnosis of bipolar disorder is suggested in some patients. PMID- 8006245 TI - The lymphoblast beta-adrenergic receptor in bipolar depressed patients: effect of chronic incubation with lithium chloride. AB - We have recently reported a study of beta-adrenergic receptor binding characteristics in lymphoblast cell lines derived from patients with bipolar disorder (BD) and healthy, matched control subjects. In the present study we have investigated the effects of incubating cells from the same subjects with lithium chloride (1 mM) for 7 days prior to assay. There was no difference in beta adrenergic receptor number between control and BD cell lines and incubation with lithium had no effect on receptor number in either group. Exposure of the cells to isoprenaline (1 nM) for 24 h immediately prior to assay caused significantly less down-regulation in BD cells (15 +/- 5%) than control cells (39 +/- 4%), as described previously. Incubation with lithium significantly increased the down regulation response to isoprenaline in BD cells (39 +/- 6%) but not in control cells (30 +/- 7%). After lithium, the agonist-induced decrease in beta-AR number in BD cells was no longer significantly different from that in control cells. We conclude that lithium selectively enhanced the agonist down-regulation of beta adrenergic receptors in cells derived from patients with bipolar disorder. The functional significance of this result and the potential biochemical mechanisms responsible for this effect are discussed. PMID- 8006247 TI - Brofaromine in treatment-resistant depressed patients--a comparative trial versus tranylcypromine. AB - In a controlled clinical inpatient trial (n = 93) comparing the efficacy and safety of brofaromine versus tranylcypromine for 6 weeks in treatment-resistant major depressed patients, the two drugs were found to be of comparable afficacy and tolerability. The response rate (a 50% reduction) on the Hamilton Scale for Depression (HAMD) in both groups was about 73%. The most common side effects in the brofaromine group were sleep disorders, hypotension, tremor and dryness of mouth; and in the tranylcypromine group sleep disorders, fatigue, hypotension, tremor and vertigo. Methodological and practical clinical implications of the results are discussed. PMID- 8006246 TI - Eating behaviour and depression before and after antidepressant treatment: a prospective, naturalistic study. AB - Eating behaviour of severely depressed patients was assessed before (n = 56), after acute (n = 46) and during maintenance (n = 35) treatment and compared to matched normal controls in order to investigate the behavioural mechanisms underlying the weight gain induced by antidepressants. Assessments included food intake, appetite and food preferences. Before treatment, there was a decrease in appetite and in food intake with a relative excess of carbohydrates and a preference for sweets. Maintenance treatment was associated with substantial weight gain. All differences in eating behaviour between patients and controls disappeared, with the exception of a decrease in appetite in a subgroup of less improved patients. These results suggest that antidepressant treatment induces weight gain by mechanisms that are largely independent of their action on mood. PMID- 8006248 TI - Brofaromine versus lithium addition to maprotiline. A double-blind study in maprotiline refractory depressed outpatients. AB - Depressed outpatients (n = 51) resistant to treatment with maprotiline were treated in a blind, randomized, single-centre study, for 6 weeks with either the reversible and selective monoamine oxidase A-inhibitor (MAO-A-I), brofaromine or lithium addition to maprotiline. The Hamilton Rating Scale for Depression was scored by an independent rater before and after the 6 week treatment period. No significant differences in efficacy were found between the two treatment regimes. In the patients who completed the trial, brofaromine was well tolerated with the exception of insomnia. Anticholinergic effects as well as thyroid dysfunctions (17 out of 20) were more frequent in the maprotiline/lithium group. PMID- 8006249 TI - The Asymptomatic Cardiac Ischemia Pilot (ACIP) study: design of a randomized clinical trial, baseline data and implications for a long-term outcome trial. AB - OBJECTIVES: The primary objectives of the Asymptomatic Cardiac Ischemia Pilot were 1) to compare the 12-week efficacy of three treatment strategies to suppress cardiac ischemia, and 2) to assess the feasibility of a prognosis trial in patients with asymptomatic cardiac ischemia. BACKGROUND: Cardiac ischemia has been associated with increased morbidity and mortality. However, most cardiac ischemia is asymptomatic, and although therapeutic strategies ranging from no medication to revascularization are being used to treat ischemia, no prospective study evaluating different treatment strategies has been reported. METHODS: Patients with angiographically documented coronary artery disease and ischemia on exercise and ambulatory electrocardiogram (ECG) in 11 clinical units were randomized to receive angina-guided medical therapy, angina-guided plus ambulatory ECG ischemia-guided medical therapy or revascularization (coronary angioplasty or bypass surgery). Patients were also randomized to receive either diltiazem plus isosorbide dinitrate or atenolol plus nifedipine when possible. After anti-ischemic medication adjustment to control angina, blinded medication was adjusted in the medical therapy groups to eliminate ischemia in the ischemia guided group. The primary outcome was the absence of ischemia at 12 weeks. Follow up was scheduled for 1 year. RESULTS: A total of 1,959 patients were screened by ambulatory ECG monitoring; 982 (49%) had asymptomatic ischemia, and 618 (65%) were enrolled in the study. Most patients were men, were > 60 years old and had two or more ischemic episodes, early positive exercise tests and multivessel disease. CONCLUSIONS: Design and baseline data for a pilot study of ischemia treatment strategies are described. PMID- 8006250 TI - Functional capacity after cardiac surgery in elderly patients. AB - OBJECTIVES: This study was performed to determine whether cardiac surgery improves functional capacity in patients > 70 years of age and to identify factors associated with good and poor functional results in this age group. BACKGROUND: Cardiac surgery has been used increasingly among older patients, but the effectiveness of surgery in this age group remains controversial. METHODS: Self-reported functional capacity was assessed by the Duke Activity Status Index preoperatively and again 1 year after coronary artery bypass or valve replacement surgery in a total of 199 patients with a mean age of 76 years (range 70 to 91). RESULTS: Functional capacity improved significantly after surgery (mean Duke Activity Status Index 27.9 at baseline vs. 36.8 at 12 months, p < 0.001), with improvements in most patients (74%). Six preoperative factors were independent predictors of less improvement in functional capacity between baseline and 1 year: smoking, female gender, higher Charlson comorbidity index, syncope, previous cardiac operation and older age. Postoperative complications were also a highly significant predictor of lower functional capacity at 1 year. CONCLUSIONS: Most older patients have meaningful improvements in functional capacity after cardiac surgery, and clinical factors appear to modify the degree of improvement attainable. PMID- 8006251 TI - Identification of multivessel coronary artery disease by exercise echocardiography. AB - OBJECTIVES: This study examined the ability of exercise echocardiography to identify multivessel coronary artery disease and ascertain its incremental value when combined with clinical and exercise test variables. BACKGROUND: Although exercise echocardiography has been shown to be accurate for the detection of coronary artery disease, little is known about its utility for identifying multivessel involvement, and its incremental value when combined with clinical and exercise test variables has not been studied. METHODS: One hundred fifty consecutive patients were selected on the basis of having had an exercise echocardiographic and a coronary angiographic study within 6 months without any revascularization procedure. Significant coronary artery disease (> or = 50% diameter stenosis in any major coronary artery) was present in 117 patients, and multivessel (two- or three-vessel) disease was present in 90 patients. The exercise echocardiographic studies were reviewed by an experienced observer unaware of the results of the coronary angiogram. RESULTS: The overall sensitivity and specificity of exercise echocardiography for the identification of multivessel disease were 73% and 70%, respectively. A stepwise logistic regression analysis identified the number of abnormal regions on the postexercise images as the strongest independent predictor of multivessel disease; also significant were a history of myocardial infarction and ST segment depression of at least 2 mm on the peak exercise electrocardiogram. CONCLUSIONS: Exercise echocardiography adds independent and incremental information to clinical and exercise test variables for identifying multivessel coronary artery disease. PMID- 8006252 TI - Effects of treatment strategies to suppress ischemia in patients with coronary artery disease: 12-week results of the Asymptomatic Cardiac Ischemia Pilot (ACIP) study. AB - OBJECTIVES: The Asymptomatic Cardiac Ischemia Pilot (ACIP) study was initiated to determine the feasibility of a large trial in evaluating the effects of treatment of ischemia on outcome (mortality and myocardial infarction). The study was designed to examine the effects of medical treatment to control angina compared with treatment strategies guided by ambulatory electrocardiographic (ECG) ischemia or coronary anatomy. BACKGROUND: Treatments to suppress ischemia (asymptomatic and symptomatic) have not been evaluated in a large prospective, randomized trial. Before undertaking such a trial, issues about recruitment and treatment strategies must be addressed. METHODS: The 618 enrolled patients had coronary artery disease suitable for revascularization, ischemia on stress test and asymptomatic ischemia on ambulatory ECG. Patients were assigned randomly to one of three treatment strategies: 1) angina-guided medical strategy with titration of anti-ischemic medication to relieve angina (angina-guided strategy); 2) angina-guided plus ambulatory ECG ischemia-guided medical strategy with titration of anti-ischemic medication to eliminate both angina and ambulatory ECG ischemia (ischemia-guided strategy); and 3) revascularization by angioplasty or bypass surgery (revascularization strategy). RESULTS: Ambulatory ECG ischemia was no longer present at the week 12 visit in 39% of patients assigned to the angina guided strategy, 41% of patients assigned to the ischemia-guided strategy and 55% of patients assigned to the revascularization strategy. All strategies reduced the median number of episodes and total duration of ST segment depression during follow-up ambulatory ECG monitoring. Revascularization was the most effective strategy. Treadmill test results were concordant with those of ambulatory ECG monitoring. For most patients in the two medical strategies, angina was controlled with low to moderate doses of anti-ischemic medication, and the majority of patients (65%) in the revascularization strategy did not require medication for angina. CONCLUSIONS: This pilot study demonstrated that cardiac ischemia can be suppressed in 40% to 55% of patients with either low or moderate doses of medication or revascularization and that a large trial is feasible. PMID- 8006253 TI - Exercise echocardiography: coming of age. PMID- 8006254 TI - Detection of coronary artery disease by digital stress echocardiography: comparison of exercise, transesophageal atrial pacing and dipyridamole echocardiography. AB - OBJECTIVES: This study assessed and compared the diagnostic potential of exercise, transesophageal atrial pacing and dipyridamole stress echocardiography in a clinical setting. BACKGROUND: Although they have been widely studied, no data exist with regard to comparisons of these procedures in a head-to-head study in different clinical settings. METHODS: One hundred four consecutive patients with suspected coronary artery disease undergoing coronary angiography and with no previous myocardial infarction or rest left ventricular wall motion abnormalities underwent digital posttreadmill, transesophageal atrial pacing and dipyridamole echocardiography. RESULTS: Feasibility of digital exercise echocardiography was 84%; 8 of 88 remaining patients had a nondiagnostic exercise echocardiographic test (inadequate exercise or imaging). In 80 patients with feasible and diagnostic digital exercise echocardiography, sensitivity, specificity and accuracy were, respectively, 89%, 91% and 90%. Eighty of the 104 patients underwent transesophageal atrial pacing and dipyridamole echocardiography. Feasibility of the alternative stress procedures was 77% for transesophageal atrial pacing and 96% for dipyridamole. In 60 patients successfully undergoing both alternative stress procedures, sensitivity and specificity were 83% and 76% for atrial pacing and 43% and 92% for dipyridamole echocardiography, respectively. In the group of 24 patients with nondiagnostic exercise echocardiography and consequent indication to alternative stress procedures, accuracy of transesophageal atrial pacing was higher than that of dipyridamole echocardiography (73% vs. 45%, p = 0.06). CONCLUSIONS: Because of its higher diagnostic potential and additional functional information, exercise is the stress of choice when stress echocardiography is used to detect the presence of coronary artery disease. Alternative stresses can be used in patients with nondiagnostic exercise echocardiography. Transesophageal and dipyridamole echocardiography differ in feasibility and diagnostic reliability (higher sensitivity of transesophageal atrial pacing, higher specificity of dipyridamole). These characteristics must be considered when selecting procedures to be used as alternatives to exercise. PMID- 8006255 TI - Clinical utility of transthoracic two-dimensional and Doppler echocardiography. AB - OBJECTIVES: The purpose of this study was to determine the value of contemporary echocardiography for patient diagnosis and management in clinical practice. BACKGROUND: Although the use of echocardiography is growing rapidly, there is little information about its clinical utility. METHODS: A prospective observational study was performed at a community-based, tertiary care teaching hospital. Physicians were interviewed before and after learning the result of their patients' echocardiographic examination. Chart reviews were performed to confirm reports of new diagnoses and treatments that resulted from echocardiography. RESULTS: Physician interviews were successfully completed for 244 (49%) of 497 inpatients and 101 (30%) of 336 outpatients. Among patients with moderate or greater mitral regurgitation, the diagnosis of "clinically significant" mitral regurgitation was unsuspected in 5 (31%) of 16 outpatients and 28 (60%) of 47 inpatients. Among the patients with left ventricular wall motion abnormalities, the result was unsuspected in 7 (50%) of 14 outpatients and 18 (22%) of 81 inpatients. As assessed by chart review, echocardiography produced a definite new diagnosis in 25 inpatients (10%) and 5 outpatients (5%) and was responsible for changes in pharmacologic treatment in at least 16 inpatients (7%) and 2 outpatients (2%). CONCLUSIONS: The echocardiogram commonly provided information that was unexpected. This information provided a definite new diagnosis or treatment in a smaller proportion of the patients. Further research is necessary to define the appropriate yield that would warrant echocardiography on the basis of both clinical and cost-effectiveness criteria. PMID- 8006256 TI - Prognostic value of Doppler transmitral flow patterns in patients with congestive heart failure. AB - OBJECTIVES: This study was designed to determine whether Doppler echocardiographic transmitral flow patterns can predict cardiac mortality in patients with congestive heart failure. BACKGROUND: Previous studies have indicated that Doppler transmitral flow patterns are related to New York Heart Association functional class and exercise capacity in patients with congestive heart failure. However, the prognostic significance of these flow patterns is not known. METHODS: We analyzed the relation of transmitral flow patterns and cardiac mortality in 100 consecutive patients (76 men, 24 women; mean [+/- SD] age 60 +/- 11 years) with congestive heart failure symptoms and left ventricular ejection fraction < 40%. At the time of entry into the study, functional class and ejection fraction by radionuclide angiography were determined, and Doppler echocardiography was performed in all patients. Transmitral flow was obtained from the apical four-chamber view at the mitral annulus level. Measurements included early (E) and atrial (A) filling velocities, E/A ratio and deceleration time of the E wave. The patients were assigned to two groups according to E/A ratio or deceleration time of transmitral flow patterns, or both: a non restrictive group (42 patients) with E/A < or = 1 or E/A = 1 to 2 and deceleration time > 140 ms, and a restrictive group (58 patients) with E/A > or = 2 or E/A = 1 to 2 and deceleration time < or = 140 ms. RESULTS: Of 100 patients, 26 died during a mean follow-up period of 16 +/- 8 months. The cumulative cardiac mortality rate determined by the Kaplan-Meier method was 14% at 1 year and 35% at 2 years. Cox proportional hazards model analysis revealed that transmitral flow (restrictive vs. nonrestrictive, chi-square 6.99, p = 0.008), patient gender (female vs. male, chi-square 4.59, p = 0.03) and New York Heart Association functional class (IV vs. II, chi-square 3.95, p = 0.05) were significantly related to cardiac mortality in patients with congestive heart failure. Mortality rate in the restrictive group was markedly higher than that in the nonrestrictive group at 1 year (19% vs. 5%, respectively, p < 0.05) and at 2 years (51% vs. 5%, respectively, p < 0.01) by log-rank test. Relative risk for cardiac death was estimated as 4.1 at 1 year and 8.6 at 2 years in the restrictive group compared with the nonrestrictive group. CONCLUSIONS: In patients with congestive heart failure, a restrictive transmitral flow pattern, female gender and advanced functional class are predictive of higher cardiac mortality. The restrictive transmitral flow pattern by Doppler echocardiography is the single best clinical predictor for cardiac death in patients with congestive heart failure. PMID- 8006258 TI - Adult myocyte hyperplasia: divided they fail? PMID- 8006257 TI - Myocyte nuclear and possible cellular hyperplasia contribute to ventricular remodeling in the hypertrophic senescent heart in humans. AB - OBJECTIVES: The present investigation was designed to evaluate the growth reserve capacity of the aged and senescent myocardium. BACKGROUND: Aging affects the ability of the heart to sustain alterations in ventricular loading, and this phenomenon may be coupled with attenuation of the hypertrophic reaction of the myocardium. However, because myocyte cellular hyperplasia has been documented experimentally in the old heart, a similar adaptation may also occur in humans and play a role in this process. METHODS: The changes in number and size of ventricular myocytes were measured quantitatively in pathologic hearts of elderly subjects. Morphometric methodologies were applied to the analysis of 13 hypertrophic hearts obtained at autopsy from patients 80 +/- 4 (mean +/- SD) years old. An identical number of nonhypertrophic hearts collected from subjects 76 +/- 7 years old were used as control hearts. RESULTS: A 71% increase in left ventricular weight was associated with a 33% increase in average myocyte cell volume per nucleus and a 36% augmentation in the total number of myocyte nuclei in the ventricular myocardium. However, a 55% increase in right ventricular weight was the result of a 59% increase in the aggregate number of myocyte nuclei, with no change in myocyte cell volume. These cellular processes were associated with a 95% and 83% enlargement of the myocardial interstitium in the left and right ventricle, respectively. CONCLUSIONS: Myocyte nuclear and possibly cellular hyperplasia appear to be the prevailing growth mechanism of the overloaded aging myocardium. Proliferation of myocyte nuclei and connective tissue accumulation are the major determinants of ventricular remodeling in the hypertrophic senescent heart. PMID- 8006260 TI - Left atrial appendage function and thrombus formation in atrial fibrillation flutter: a transesophageal echocardiographic study. AB - OBJECTIVES: The purpose of this study was to investigate left atrial appendage size, function and thrombus prevalence in patients with atrial "fibrillation flutter." BACKGROUND: Thrombus formation and peripheral embolization in atrial fibrillation are related to left atrial appendage dysfunction. Embolization occurs less frequently in atrial flutter. It is not known whether the atrial appendage in fibrillation-flutter, which has an intermediate appearance on the surface electrocardiogram (ECG), has distinct characteristics that could affect thrombus formation. METHODS: Sixty-one patients with atrial tachyarrhythmias underwent transesophageal echocardiographic examination of the left atrial appendage. Appendage area, peak emptying velocity and the presence of thrombus and spontaneous echo contrast were determined. The results for 14 patients with fibrillation-flutter (based on ECG fibrillatory wave characteristics) were compared with those for 30 patients with atrial fibrillation and 17 patients with atrial flutter. RESULTS: Both fibrillation-flutter and atrial fibrillation were associated with chaotic appendage flow patterns with similarly low peak emptying velocities (18 +/- 8 and 17 +/- 10 cm/s, mean +/- 1 SD, respectively). Atrial flutter was associated with a regular pattern of appendage contraction and a significantly higher peak emptying velocity (42 +/- 18 cm/s, p < 0.0001). Mean appendage area was similar for fibrillation-flutter and fibrillation (6.3 +/- 2.2 and 6.7 +/- 2.1 cm2, respectively) but was significantly smaller for atrial flutter (5.3 +/- 1.4 cm2, p < 0.05). The prevalence of left atrial appendage thrombus was similar for fibrillation-flutter and atrial fibrillation (40% and 29%, respectively), whereas no patient with atrial flutter had a thrombus (p < 0.05). Similarly, the presence of spontaneous echo contrast was higher for fibrillation-flutter (50%) and atrial fibrillation (40%) than for atrial flutter (6%, p < 0.05). CONCLUSIONS: Left atrial appendage size and function in atrial fibrillation-flutter are indistinguishable from those of typical atrial fibrillation, and the frequency of thrombus and spontaneous echo contrast is similarly high. This is in contrast to atrial flutter, which is characterized by a smaller, more contractile left atrial appendage and a lower frequency of thrombus and spontaneous echo contrast. PMID- 8006259 TI - Accurate measurement of the transmitral gradient in patients with mitral stenosis: a simultaneous catheterization and Doppler echocardiographic study. AB - OBJECTIVES: This study compared the accuracy of Doppler echocardiography with that of conventional cardiac catheterization in the measurement of transmitral gradients in patients with mitral stenosis. BACKGROUND: Simultaneous measurement of left atrial and left ventricular pressures is the most accurate method for determination of the mean mitral valve gradient in patients with mitral stenosis. Because of the inherent risks of transseptal catheterization, pulmonary capillary wedge pressure has been used in many invasive laboratories for determination of the mean mitral valve gradient. Recent studies have observed significant errors when pulmonary capillary wedge pressure was used for these measurements. Doppler echocardiography provides a noninvasive alternative for measurement of the transmitral gradient, but its relative accuracy has remained unclear. METHODS: Seventeen patients with mitral stenosis who underwent transseptal cardiac catheterization had simultaneous measurement of 1) transmitral gradient by direct left atrial and left ventricular pressures, 2) transmitral gradient by pulmonary capillary wedge and left ventricular pressures, and 3) transmitral gradient by Doppler echocardiography. RESULTS: Transmitral gradient measured by pulmonary capillary wedge and left ventricular pressures significantly overestimated the gradient obtained by direct measurement of left atrial pressure, with a mean (+/- SD) difference of 3.3 +/- 3.5 mm Hg (or 53%). Correcting the pulmonary capillary wedge pressure for the phase shift resulted in better correlation, but a consistent overestimation still remained, with a mean difference of 2.5 +/- 2.9 mm Hg (or 43%). The best correlation with the smallest variability was comparison of the Doppler-derived mean gradient with the gradient from direct measurement of left atrial and left ventricular pressures, with a mean difference of 0.2 +/- 1.2 mm Hg. CONCLUSIONS: Compared with the transmitral gradient obtained by direct measurement of left atrial and left ventricular pressures, the Doppler-derived gradient is more accurate than that obtained by conventional cardiac catheterization and should be considered the reference standard. PMID- 8006261 TI - Left atrial function and ventricular filling in hypertensive patients with paroxysmal atrial fibrillation. AB - OBJECTIVES: We evaluated left atrial dimensions and function, as well as left ventricular structure and filling, in hypertensive patients with paroxysmal atrial fibrillation. BACKGROUND: In hypertensive patients, left atrial dilation and enhanced volume transport may facilitate arrhythmias. METHODS: Left ventricular two-dimensional and M-mode echocardiograms and pulsed Doppler echocardiography of transmitral flow were performed in 17 consecutive primary hypertensive patients with paroxysmal atrial fibrillation (group EHf) and in 34 patients with high blood pressure without this arrhythmia (group EH). Seventeen normal subjects (group N) were also investigated. Groups were matched for age and gender. RESULTS: The EH and EHf groups had similar systolic arterial pressures ([mean +/- SD] group EH 185 +/- 27, group EHf 173 +/- 25 mm Hg, p = NS) and left ventricular mass index (group EH 154 +/- 55, group EHf 131 +/- 57.8 g/m2, p = NS), and their M-mode left ventricular systolic wall stress and fractional shortening were comparable to those of normal subjects. M-mode left atrial maximal (group N 37.8 +/- 6, group EH 37.9 +/- 4.6, group EHf 44.6 +/- 6.7 mm, p < 0.05 for group EHf vs. groups N and EH) and minimal diameters and the diameter preceding atrial contraction (group N 31 +/- 3.6, group EH 34.5 +/- 5, group EHf 40.4 +/- 6.9 mm, p < 0.001 for group EHf vs. group N; p < 0.05 for group EHf vs. group EH) were greater in group EHf than in group EH and group N subjects, whereas only the latter diameter was increased in group EH (p < 0.05 vs. group N), so that left atrial fractional shortening was higher than normal only in group EH (group N 10.8 +/- 4.4%, group EH 14.6 +/- 5.5%, group EHf 9.3 +/- 5.3%; group EH vs. group N, p < 0.05; group EHf vs. group EH, p < 0.05). The pulsed Doppler ratio of early to late transmitral flow rates (E and A wave velocity/time integrals x mitral annulus area) was lower than normal in group EH (group N 2.9 +/- 2.2, group EH 1.75 +/- 0.8, group EHf 2.8 +/- 0.8; group EH vs. group N, p < 0.05; group EHf vs. group EH, p < 0.001; group EHf vs. group N, p = NS) and was "normalized" in group EHf, early flow being increased in this group (group N 42 +/- 13, group EH 39 +/- 29, group EHf 60 +/- 17 ml; group EHf vs. group N, p < 0.05; group EHf vs. group EH, p < 0.05). CONCLUSIONS: These results suggest that the occurrence of paroxysmal atrial fibrillation in hypertension is associated with enlargement of the left atrium, depression of its contractile function and "normalization" of the pattern of left ventricular filling and is independent of left ventricular hypertrophy and systolic wall stress. The mechanisms linking these variables remain undefined. PMID- 8006263 TI - Asymmetry of retrograde conduction and reentry within the His-Purkinje system: a comparative analysis of left and right ventricular stimulation. AB - OBJECTIVES: The purpose of this study was to delineate retrograde His-Purkinje system conduction and reentry (V3 phenomenon) during left ventricular extrastimulation and compare them with right ventricular extrastimulation. BACKGROUND: The V3 phenomenon has been well described in the past during right ventricular extrastimulation; however, it has not been studied systematically during left ventricular extrastimulation. METHODS: Left and right ventricular pacing were performed in 13 patients. Retrograde and anterograde routes of impulse propagation were determined on the basis of the sequence of His (H) and right bundle (RB) potentials, H-RB intervals, as well as the QRS configuration and axis of V3 beats. RESULTS: During right ventricular pacing, retrograde conduction of V2, when discernible, occurred exclusively through the left bundle at all coupling intervals equal to or shorter than the His-Purkinje relative refractory period, with the exception of two isolated beats. During left ventricular extrastimulation, His bundle activation was through the left bundle in nine patients and through the right or left bundle in three other patients. In one patient, the route could not be determined. The V3 phenomena occurred in eight patients during right ventricular pacing. Seven patients had a left bundle branch block pattern QRS configuration, and one had a right bundle branch block pattern configuration. V3 beats occurred in five patients during left ventricular apex pacing: left bundle branch block pattern configuration in one patient and right bundle branch block pattern configuration in four. In three of these four patients, the reentry was interfascicular and limited to the left bundle branch system. CONCLUSIONS: The left-sided His-Purkinje system is the preferred retrograde route of impulse propagation during both left and right ventricular extrastimulation. Reentry within the His-Purkinje system elicited by right ventricular extrastimulation involves both bundle branches, whereas this reentry tends to occur within the left-sided His-Purkinje system during left ventricular pacing. PMID- 8006262 TI - Comparison of biphasic and monophasic waveforms in epicardial atrial defibrillation. AB - OBJECTIVES: Because biphasic waveforms have previously been shown to be more efficient than monophasic waveforms in defibrillation of the ventricle, we compared the efficiency of the two waveforms in defibrillation of the atria. BACKGROUND: The development of an implantable atrial defibrillator would offer significant advantages over current approaches to the management of atrial fibrillation. Patient tolerance of atrial shocks from such a device, however, would depend critically on the deployment of an efficient waveform. METHODS: Both the monophasic and biphasic shocks were of 8-ms duration, and the biphasic was a dual-capacitor waveform with equal first- and second-phase duration and leading edge voltage. One hundred randomized atrial shocks were evaluated in 21 patients during cardiopulmonary bypass. Atrial fibrillation was induced by the application of alternating current. Atrial shocks were delivered through customized, contoured epicardial paddles applied to the posterior left atrial wall (surface area 11 cm2) and to the anterior right atrial wall (surface area 26 cm2). RESULTS: For the monophasic waveform the delivered energy (joules) associated with 50% success (E50) was 1.44 J (95% confidence interval [CI] 0 to 11.2) and with 80% (E80) success 3.9 J (95% CI 2.42 to 109.8); for the biphasic waveform 50% success was achieved with 0.37 J (95% CI 0.36 to 0.38) (p = NS) and 80% success with 0.57 J (95% CI 0.56 to 0.58) (p < 0.05). CONCLUSIONS: A biphasic waveform is more efficient than a monophasic waveform in atrial defibrillation. This may have implications for the development of an implantable atrial defibrillator for paroxysmal atrial fibrillation in addition to improvement of elective transthoracic and endocardial cardioversion of chronic atrial fibrillation. PMID- 8006264 TI - Outcome of pregnancy after the Mustard operation for transposition of the great arteries with intact ventricular septum. AB - OBJECTIVES: This study examined the outcome of pregnancy in patients with transposition of the great arteries and an intact ventricular septum after a Mustard operation. BACKGROUND: Before the introduction of surgical treatment, most children with transposition of the great arteries died in early infancy. A number of these patients have now reached their reproductive years. There is little information about the effect of pregnancy on cardiovascular status, particularly the ability of the right ventricle to adjust to the hemodynamic changes of pregnancy. The outcome for the offspring and their risk of congenital heart disease are also unknown. METHODS: Twenty-three female late survivors after the Mustard operation > 15 years of age were reviewed in relation to the occurrence of pregnancy and its outcome. Serial echocardiographic estimates of right ventricular volume during pregnancy were made in three local patients. RESULTS: Nine women had 15 pregnancies. They were asymptomatic before pregnancy and remained free from cardiac symptoms during each pregnancy. Right ventricular volume in the three patients studied increased during pregnancy but returned to normal at 8 to 11 weeks postpartum. There were 12 live births, 2 spontaneous abortions and 1 intrauterine death. None of the liveborn infants had evidence of congenital heart disease. CONCLUSIONS: In this small group of women with good quality late survival after a Mustard operation, pregnancy was well tolerated. We suspect that the incidence of congenital heart disease in infants of mothers with transposition of the great arteries will be at the lower end of the range for mothers with different types of congenital heart disease, but further data will be needed to confirm this. PMID- 8006265 TI - Persistent hyperdynamic cardiovascular state at rest and during exercise in children after successful repair of coarctation of the aorta. AB - OBJECTIVES: The purposes of this study were to evaluate left ventricular performance and contractility at rest and during exercise to determine mechanisms and correlates for alterations in performance and blood pressure in pediatric patients after successful repair of coarctation of the aorta. BACKGROUND: Blood pressure and left ventricular function are elevated in children despite successful repair. The mechanisms for these changes are not understood. METHODS: Thirty asymptomatic pediatric patients with successful coarctation repair (mean age [+/- SD] 12.5 +/- 4 years) underwent echocardiographic determination of left ventricular mass, performance (shortening fraction), preload (indexed diastolic dimension), afterload (end-systolic wall stress), contractility (velocity of circumferential fiber shortening/wall stress relation) and Doppler gradient at rest and during exercise. Data were compared with those of 24 control subjects (mean age 21.0 +- 4 years). Because of the age discrepancy between groups, age dependent echocardiographic data were indexed by body surface area. RESULTS: The mean age at operation was 5 +/- 4 years, and the average follow-up period was 7.5 +/- 3 years. The average blood pressure gradient between upper and lower limbs was 4 mm Hg. Left ventricular mass was higher in the postoperative group than in the control group (1.58 vs. 1.31 g/ht2.7, p = 0.04), as were values at rest for performance (44% vs. 31%, p = 0.0001), preload (3.9 vs. 3.7 cm/body surface area0.5), indexes systolic blood pressure (1.05 vs. 0.91, p = 0.0001) and contractility (0.23 vs. -0.05 circumferences/s, p= 0.001). Afterload was lower at rest (36 vs. 52 g/cm2, p = 0.0004). These differences between groups persisted during and after exercise. Contractility underwent an exaggerated increase after exercise in the postoperative group. CONCLUSIONS: Left ventricular performance in children after coarctation repair is higher at rest and during exercise than in control subjects as a result of higher preload and contractility and lower afterload. These changes may be due to associated hypertrophy. Persistent postoperative hypertension may be due to a hyperdynamic, hypercontractile state caused by residual gradients manifested only during exertion. PMID- 8006266 TI - Active compression-decompression resuscitation: effect on resuscitation success after in-hospital cardiac arrest. AB - OBJECTIVES: The purpose of this study was to test the hypothesis that active compression-decompression would improve resuscitation success in human subjects after cardiac arrest. BACKGROUND: Active compression-decompression cardiopulmonary resuscitation is a new method that improves cardiopulmonary hemodynamic function in animal models and humans after cardiac arrest. METHODS: We conducted a prospective randomized clinical trial in patients with in-hospital cardiac arrest. Patients were assigned to receive standard manual or active compression-decompression cardiopulmonary resuscitation. The primary study end points were spontaneous return of circulation, 24-h survival and survival to hospital discharge. RESULTS: Fifty-three consecutive patients after cardiac arrest undergoing 64 resuscitation attempts were studied (30 women, 23 men; mean [+/- SD] age 71 +/- 13 years, range 38 to 96). Spontaneous return of circulation was observed in 24 (47%) of 53 patients and was increased in patients receiving active compression-decompression compared with those receiving standard manual cardiopulmonary resuscitation (15 [60%] of 25 vs. 9 [32%] of 28, respectively, p = 0.042); 24-h survival was increased (12 [48%] of 25 vs. 6 [21%] of 28, respectively, p = 0.041); and there was a trend toward improved survival to hospital discharge (6 [24%] of 25 vs. 3 [11%] of 28, respectively, p = 0.198) when active compression-decompression was compared with standard manual cardiopulmonary resuscitation. CONCLUSIONS: Active compression-decompression cardiopulmonary resuscitation improves return of spontaneous circulation and 24-h survival after in-hospital cardiac arrest. Active compression-decompression cardiopulmonary resuscitation appears to be a beneficial adjunct to standard manual cardiopulmonary resuscitation. PMID- 8006267 TI - Is there evidence in support of the ischemia suppression hypothesis? PMID- 8006268 TI - Abnormalities in sympathoneuronal regulation are localized to failing myocardium in rabbit heart. AB - OBJECTIVES: This study investigated the differences in sympathoneuronal regulation between acute left ventricular failure and chronic biventricular failure to determine whether an increase in plasma norepinephrine concentration plays a primary role in the genesis of the desensitization phenomenon in heart failure. BACKGROUND: It remains to be determined whether plasma norepinephrine plays a primary role in the pathogenesis of sympathetic desensitization in heart failure in vivo. METHODS: Acute left ventricular failure was induced by aortic regurgitation in seven rabbits. Chronic heart failure was induced by adriamycin treatment in another seven rabbits. RESULTS: Cardiac output was lower in rabbits with aortic regurgitation than in seven sham-operated rabbits. Left ventricular end-diastolic pressure was higher in rabbits with aortic regurgitation, but no significant difference in right ventricular end-diastolic pressure was observed. Beta-adrenoceptor density and norepinephrine concentration in the left ventricular myocardium were lower in rabbits with aortic regurgitation; no such differences were observed for the right ventricular myocardium. Cardiac output was lower in adriamycin-treated rabbits than in seven control rabbits. Both left and right ventricular end-diastolic pressures were higher in experimental rabbits than in control rabbits. Myocardial beta-adrenoceptor density and norepinephrine content were reduced in both ventricles. CONCLUSIONS: In chronic heart failure induced by adriamycin, sympathoneuronal activity was altered in both ventricles, whereas in acute left ventricular failure induced by aortic regurgitation, sympathoneuronal activity was affected only in the left ventricle despite a similar increase in plasma norepinephrine concentration in both animal models. Local abnormalities in sympathoneuronal regulation in failing myocardium therefore appear to be responsible for these phenomena. PMID- 8006269 TI - A new approach for the quantification of complex lesion morphology: the gradient field transform; basic principles and validation results. AB - OBJECTIVES: This report describes the basic principles and the results from clinical evaluation studies of a new algorithm that has been designed specifically for the quantification of complex coronary lesions. BACKGROUND: Currently used edge detection algorithms in quantitative coronary arteriography, such as the minimum cost algorithm, are limited in the precise quantification of complex coronary lesions characterized by abruptly changing shapes of the obstruction. METHODS: The new algorithm, the gradient field transform, is not limited in its search directions and incorporates the directional information of the arterial boundaries. To evaluate its accuracy and precision, 11 tubular phantoms (sizes 0.6 to 5.0 mm), were analyzed. Second, angiographic images of 12 copper phantoms with U-shaped obstructions were analyzed by both the gradient field transform and the minimum cost algorithm. Third, 25 coronary artery segments with irregularly shaped obstructions were selected from 19 routinely acquired angiograms. RESULTS: The plexiglass phantom study demonstrated an accuracy and precision of -0.004 and 0.114 mm, respectively. The U-shaped copper phantoms showed that the gradient field transform performed very well for short, severe obstructions, whereas the minimum cost algorithm severely overestimated the minimal lumen diameter. From the coronary angiograms, the intraobserver variability in the minimal lumen diameter was found to be 0.14 mm for the gradient field transform and 0.20 mm for the minimum cost algorithm. CONCLUSIONS: The new gradient field transform eliminates the limitations of the currently used edge detection algorithms in quantitative coronary arteriography and is therefore particularly suitable for the quantification of complex coronary artery lesions. PMID- 8006270 TI - Effects of long-term right ventricular apical pacing on left ventricular perfusion, innervation, function and histology. AB - OBJECTIVES: The purpose of this study was to better understand the effects of long-term right ventricular pacing on left ventricular perfusion, innervation, function and histology. BACKGROUND: Long-term right ventricular apical pacing is associated with increased congestive heart failure and mortality compared with atrial pacing. The exact mechanism for these changes is unknown. In this study, left ventricular perfusion, sympathetic innervation, function and histologic appearance after long-term pacing were studied in dogs in an attempt to see whether basic changes might be present that might ultimately be associated with the adverse clinical outcome. METHODS: A total of 24 dogs were studied. Sixteen underwent radiofrequency ablation of the atrioventricular (AV) junction to produce complete AV block. Seven of these underwent long-term pacing from the right ventricular apex (ventricular paced group), and nine had atrial and right ventricular apical pacing with AV synchrony (dual-chamber paced group). A control group of eight dogs had sham ablations with normal AV conduction. These dogs had atrial pacing only. Regional perfusion and sympathetic innervation were studied in all dogs by imaging with thallium-201 and [I123]metaiodobenzylguanidine, respectively. The degree of innervation was also determined by assay of tissue norepinephrine levels. Left ventricular function was assessed by radionuclide ventriculography. Cardiac histology was studied with both light and electron microscopy. RESULTS: Mismatching of perfusion and innervation in the ventricular paced group was noted, with perfusion abnormalities of both the septum and free wall. Regional [I123]metaiodobenzylguanidine distribution was homogeneous. Tissue norepinephrine levels were elevated in both the ventricular and dual-chamber paced groups compared with the control group. No light or electron microscopic findings were noted in any groups. In the dual-chamber paced group, diastolic dysfunction was noted, with normal systolic function. CONCLUSIONS: Ventricular pacing resulted in regional changes in tissue perfusion and heterogeneity between perfusion and sympathetic innervation. Both ventricular and dual-chamber pacing were associated with an increase in tissue catecholamine activity. The abnormal activation of the ventricles via right ventricular apical pacing may result in multiple abnormalities of cardiac function, which may ultimately affect clinical outcome. PMID- 8006272 TI - Puppies' programmed sudden death: who is the serial killer? PMID- 8006271 TI - Inherited ventricular arrhythmias and sudden death in German shepherd dogs. AB - OBJECTIVES: This report describes a unique group of German shepherd dogs with inherited ventricular arrhythmias and sudden death. Before death, these dogs have no evidence of cardiovascular failure. BACKGROUND: There are few spontaneous animal models of sudden death that permit intensive investigation. METHODS: To determine the temporal evolution of ventricular arrhythmias and to characterize the syndrome of sudden cardiac death in these dogs, 24-h ambulatory electrocardiographic (ECG) monitoring, echocardiograms, electrophysiologic testing and breeding studies were conducted. RESULTS: The 24-h ambulatory ECGs from dogs that died showed frequent ventricular arrhythmias with rapid polymorphic ventricular tachycardia (rates > 480 beats/min). Affected dogs had a window of vulnerability for arrhythmias, with the highest incidence and severity of arrhythmias between 20 to 30 and 40 to 50 weeks of age. Affected dogs that died did not have prolongation of the QT interval over a spectrum of heart rates compared with unaffected dogs. The clinical arrhythmia was not induced in dogs during programmed electrical stimulation. Severely affected dogs monitored > 5 years did not develop any evidence of heart failure or cardiomyopathy, and no histopathologic abnormalities existed. Seventeen dogs died suddenly (age 4 to 30 months) and were either 1) found dead at first observation in the morning (n = 8), 2) observed to die during sleep (n = 4), 3) observed to die while resting after exercise (n = 3), or 4) observed to die during exercise (n = 2). All sudden deaths occurred between the end of September and April, with most (n = 11) during January and February. CONCLUSIONS: The cause of the inherited severe ventricular arrhythmias and sudden death in these young German shepherd dogs is still undetermined. A purely arrhythmic disorder is supported by the lack of cardiac pathology. Moreover, the window of vulnerability to ventricular arrhythmias and the age and circumstances of death invite speculation about the role of the autonomic nervous system. PMID- 8006273 TI - Intracardiac ultrasound determination of left ventricular volumes: in vitro and in vivo validation. AB - OBJECTIVES: This study was designed to assess the feasibility of calculating left ventricular volumes using intracardiac ultrasound. BACKGROUND: Previous studies have validated transthoracic echocardiographic determinations of left ventricular volumes and have indicated the superiority of Simpson rule reconstruction algorithms. The feasibility of imaging the left ventricle with intracardiac ultrasound has also been demonstrated. METHODS: The determination of left ventricular volumes with Simpson rule reconstruction of intracardiac ultrasound images was evaluated in two phases. In vitro validation was performed in 29 animal hearts preserved in either a nondistended or distended state. Latex cast volumes were the reference standard. In vivo studies used 14 pigs, and compared intracardiac ultrasound volumes and ejection fraction with single-plane contrast angiographic values. A 12.5-MHz device was used to record short-axis images at 0.5-cm intervals. These were used to reconstruct the ventricle as a stack of cylindric elements using all imaged levels as well as sections recorded every 1 and 2 cm and at a single midventricular level. RESULTS: In the in vitro hearts, when all recorded sections were used, there was excellent agreement between intracardiac ultrasound and latex cast volumes (intracardiac ultrasound volume = 0.89 latex cast volume + 2.22, r = 0.95; intracardiac ultrasound volume = 0.97 latex cast volume + 0.91, r = 0.99) for nondistended and distended hearts, respectively. In vivo, there was again close correspondence between ultrasound and angiographic volumes (intracardiac ultrasound volume = 1.04 angiographic volume - 3.6, r = 0.91). The relation between intracardiac ultrasound and angiographic ejection fraction was fair (intracardiac ultrasound ejection fraction = 1.00 angiographic ejection fraction + 6.85, r = 0.69). Excellent correlations for the volumes were maintained as the number of cross sections was reduced to those recorded every 1 and 2 cm (r = 0.87 to 0.99). With a single midventricular site more variable but generally good correlations were obtained (r = 0.77 to 0.99). CONCLUSIONS: The application of Simpson rule reconstruction to short-axis images of the left ventricle obtained with intracardiac ultrasound provides accurate determination of left ventricular volumes in animal hearts. This technique may prove useful in the analysis of left ventricular structure and function. PMID- 8006274 TI - Transdermal nitroglycerin patch therapy reduces the extent of exercise-induced myocardial ischemia: results of a double-blind, placebo-controlled trial using quantitative thallium-201 tomography. AB - OBJECTIVES: This study prospectively evaluated whether transdermal nitroglycerin patches could limit the extent of exercise-induced left ventricular ischemia as assessed by quantitative thallium-201 tomography. BACKGROUND: Although antianginal medications are effective at reducing chest pain symptoms in patients with coronary artery disease, there is limited evidence that these agents can also reduce myocardial ischemia. METHODS: This was a randomized, double-blind, parallel, placebo-controlled trial evaluating nitroglycerin patch therapy in patients in stable condition with angiographic coronary artery disease and no previous myocardial infarction. All patients were weaned from antianginal agents and had a baseline symptom-limited treadmill test followed by thallium-201 tomography. Forty patients with perfusion defects involving > or = 5% of the left ventricle were randomized to receive either intermittent (12 h on/off) active nitroglycerin patch therapy (0.4 mg/h) or placebo. Exercise tomography was repeated a mean (+/- SD) of 6.1 +/- 1.8 days after randomization. RESULTS: Patients randomized to receive active patch therapy had a significant reduction in their total perfusion defect size (-8.9 +/- 11.1%) compared with placebo treated patients (-1.8 +/- 6.1%, p = 0.04), which was most apparent in those with the largest (> or = 20%) baseline perfusion defects (-11.4 +/- 13.4% vs. 1.0 +/- 3.6%, respectively, p < 0.02). Furthermore, 7 (33%) of 21 patients receiving active therapy had a > or = 10% decrease in their perfusion defects compared with only 1 (5%) of 19 patients randomized to receive placebo (p = 0.002). Nitrate therapy did not significantly reduce heart rate, blood pressure or double product, indicating benefit through enhancement of coronary blood flow. CONCLUSIONS: Short-term, intermittent nitroglycerin patch therapy significantly reduces myocardial ischemia, particularly in patients with large ischemic perfusion defects. Thallium-201 tomography can be used to assess sequential changes in the extent of exercise-induced left ventricular ischemia. PMID- 8006275 TI - Quantification of pericardial effusions by three-dimensional echocardiography. AB - OBJECTIVES: The purpose of this study was to examine the accuracy of three dimensional echocardiography for the quantification of asymmetric pericardial effusion volume and to compare this new technique with two-dimensional echocardiography. BACKGROUND: Quantification of pericardial effusion by two dimensional echocardiography relies on a symmetric distribution of the fluid. Three-dimensional echocardiography can quantitate volume without these limitations, but its accuracy for pericardial effusion volume has not yet been assessed. METHODS: In six open chest dogs, 41 different asymmetrically distributed pericardial effusions of known volume were created by serial infusions of fluid through a pericardial catheter. The hearts were imaged using an automated echocardiographic method that integrates three-dimensional spatial and imaging data. The surfaces of the pericardial sac and heart were then reconstructed, and the volumes of pericardial effusions were calculated. Two dimensional echocardiography was performed simultaneously, and volumes were calculated using the prolate ellipsoid method. Asymmetric distribution of the fluid was obtained by applying localized hydrostatic pressure to the pericardium. RESULTS: The volumes of pericardial effusion quantified using three-dimensional echocardiography correlated well with actual volumes (y = 1.0x - 1.4, SEE = 7.7 ml, r = 0.98). Two-dimensional echocardiography had an acceptable correlation (y = 1.0x + 2.3, SEE = 23 ml, r = 0.84), but a marked degree of variation from the true value was observed for any individual measurement. CONCLUSIONS: Three dimensional echocardiography accurately quantifies pericardial effusion volume in vivo, even when the fluid is distributed asymmetrically, whereas two-dimensional echocardiography is less reliable. This new technique may be of clinical value in quantitating pericardial effusion, especially in the serial evaluation of asymmetric or loculated effusions. PMID- 8006276 TI - Current status of myocardial perfusion imaging after percutaneous transluminal coronary angioplasty. AB - Controversy exists with regard to the diagnostic accuracy and optimal technique of myocardial perfusion imaging after coronary angioplasty. Exercise treadmill testing is inexpensive, with adequate predictive value for restenosis and clinical events in patients with single-vessel coronary angioplasty with a normal rest electrocardiogram (ECG). Myocardial tomography has advantages for assessing patients with multivessel coronary angioplasty. Exercise stress imaging is generally preferable to pharmacologic stress in patients without physical limitations after angioplasty. Delayed thallium-201 imaging and reinjection protocols may be useful to reconcile whether residual ischemia exists in "fixed" perfusion defects. Appropriately timed stress myocardial perfusion imaging 2 to 4 weeks after procedurally successful coronary angioplasty can document improved cardiac functional capacity and reduced ECG and imaging evidence of myocardial ischemia. Although routine serial postangioplasty evaluations cannot be recommended, stress myocardial imaging may be valuable in subjects with defective anginal nociception or extensive myocardium at risk in the area subtended by the angioplasty vessel. PMID- 8006277 TI - Death of a friend: "I want to die!". PMID- 8006278 TI - President's page: politics and preventive care. PMID- 8006279 TI - Regional ventricular wall motion abnormalities in tricuspid atresia after the Fontan procedure: flawed methodology may lead to a spurious finding of hypokinesia. AB - We believe that the two-frame method described by Akagi et al. cannot adequately describe the highly abnormal wall motion characteristics of these post-Fontan ventricles, and the systolic hypokinesia they describe may be spurious. Our data show that the predominant abnormality is incoordinate relaxation of the ventricular wall, which in turn prolongs the time constant of relaxation and the isovolumetric relaxation time and leads to reduced early rapid filling. Indeed, it was these abnormalities of diastolic, not systolic, function that were the strongest predictor of poor exercise performance in our study of patients late after the Fontan procedure. We strongly believe that the analysis of ventricular wall motion requires sequential data throughout the cardiac cycle, with well defined reference points concerning the timing of cardiac events, so that misinterpretation can be avoided. PMID- 8006280 TI - Eicosanoid biosynthesis in patients with stable angina: beneficial effects of very low dose aspirin. AB - OBJECTIVE: We assessed the production of eicosanoids and the effects of very low dose aspirin in patients with stable angina under basal conditions and during rapid atrial pacing. BACKGROUND: Platelet activation occurs in acute ischemic syndromes but is still controversial in stable angina. Very low dose aspirin is known to be platelet selective and can be used to test the hypothesis of the platelet origin of increased thromboxane production in stable angina. METHODS: Urinary excretion of eicosanoids was measured in 42 patients, including 24 patients with and 18 patients without coronary artery disease. The effects of 50 mg/day of aspirin were measured at rest and during pacing-induced ischemia in 10 patients with stable angina and were compared with a similar group of patients not treated by aspirin. RESULTS: Excretion of 11-dehydro-thromboxane B2 was 2.6 times higher in patients with stable angina than in healthy subjects (mean [+/- SEM] 74.8 +/- 13.0 [24 patients] vs. 29.0 +/- 5.4 [18 patients] ng/mmol of creatinine, p < 0.01). Urinary prostacyclin metabolite levels did not differ between the two groups. Treatment for 8 days with 50 mg/day of aspirin inhibited platelet cyclooxygenase, as reflected by the 97% reduction of in vitro serum thromboxane production. This aspirin regimen normalized the level of urinary thromboxane metabolites in patients with angina (17.3 +/- 3.4 ng/mmol of creatinine [10 patients], p < 0.001 from baseline level before treatment) and did not change prostacyclin metabolite levels. Atrial pacing in patients with angina not treated with aspirin caused lactate and thromboxane release into the coronary sinus. In patients with very low dose aspirin therapy, pacing did not cause thromboxane release despite inducing myocardial ischemia. However, fractional lactate extraction decreased less sharply in patients with than without aspirin therapy. CONCLUSIONS: Thromboxane production is greatly increased in patients with stable angina. Very low dose aspirin administered to these patients reduces thromboxane synthesis to normal levels, preserves prostacyclin biosynthesis and prevents acute thromboxane release into the coronary circulation during pacing induced ischemia. Our data suggest that platelets (not monocytes/macrophages) are activated in stable angina to produce thromboxane. PMID- 8006281 TI - Comparison of the effect of heparin and aspirin versus aspirin alone on transient myocardial ischemia and in-hospital prognosis in patients with unstable angina. AB - OBJECTIVES: This study compared the effects of heparin and aspirin versus aspirin alone on transient myocardial ischemia and in-hospital prognosis in patients with unstable angina. BACKGROUND: Transient myocardial ischemia occurring in patients with unstable angina is associated with an adverse prognosis. Heparin and aspirin are two drugs used frequently in the treatment of this condition, but the effect of combination therapy versus aspirin alone on transient myocardial ischemia is unknown. METHODS: Two hundred eighty-five consecutive patients with unstable angina were randomized to receive either intravenous heparin plus oral aspirin (150 mg once daily) (Group H + A) or aspirin alone (Group A). Patients also received a beta-adrenergic blocking agent, diltiazem and intravenous nitrates. ST segment monitoring was performed for the 1st 48 h of treatment. Patients were followed up for the duration of their in-hospital stay. RESULTS: One hundred fifty-four patients (30 women, mean [+/- SEM] age 58.3 +/- 0.8 years) received heparin and aspirin (Group H + A), and 131 patients (26 women, mean age 60.6 +/- 0.8 years) received aspirin only (Group A). ST segment monitoring (11,622 h) yielded 244 episodes of transient myocardial ischemia of a total duration of 7,819 min. There were no significant differences between the two treatment arms in the number of patients with transient myocardial ischemia (27 [18%] in Group H + A vs. 31 [24%] in Group A), number of episodes (96 in Group H + A vs. 148 in Group A) or total duration of transient myocardial ischemia (2,911 min in Group H + A vs. 4,908 min in Group A). The incidence of in-hospital myocardial infarction or death was significantly higher in patients with transient myocardial ischemia (53% vs. 22%, p < 0.0001). Five of the six deaths occurred in patients with transient myocardial ischemia. Event-free survival from myocardial infarction or death was similar in both treatment groups. Preadmission therapy with aspirin was associated with a lower in-hospital infarction rate (19% vs. 34%, p = 0.01). CONCLUSIONS: The presence of transient myocardial ischemia in patients with unstable angina is associated with a significantly higher incidence of myocardial infarction or death in hospital. Combined therapy with heparin and aspirin compared with aspirin alone makes no difference in the development of these events, nor does it reduce the development of transient myocardial ischemia. PMID- 8006282 TI - Directional coronary atherectomy in unstable angina. AB - OBJECTIVES: To determine whether excision of complex, ulcerated plaque improves the risk of patients with unstable angina to the level of those with stable angina, the results of directional coronary atherectomy were compared in patients with these two syndromes. BACKGROUND: The procedural results of angioplasty in the setting of unstable angina are not as favorable as those observed for chronic stable angina, presumably because thrombus-associated plaque augments the risk of abrupt closure. METHODS: Two hundred eighty-seven consecutive patients who had undergone directional atherectomy for a single new stenosis were studied. Seventy seven patients had stable angina (Group I); 110 patients had progressively worsening angina in the absence of rest or postinfarction angina (Group II); and 100 patients had rest or postinfarction angina, or both (Group III). RESULTS: Major ischemic complications (death, Q wave infarction, emergency bypass surgery) occurred more frequently in Group III (1.3% [Group I] vs. 0.9% [Group II] vs. 7% [Group III], p = 0.036). This difference was largely due to a higher incidence of emergency surgery in Group III (1.3% [Group I] vs. 0% [Group II] vs. 5% [Group III], p = 0.05). Clinical follow-up was obtained in 97% of successful procedures for a mean follow-up period of 22 months (range 9 to 52) and revealed a higher incidence of hospital admission for angina (p = 0.05) and a trend toward more bypass surgery (p = 0.09) and myocardial infarction (p = 0.16) in Group III. There was no difference in repeat percutaneous interventions among the three groups (range 19% to 24%, p = 0.75). CONCLUSIONS: These results show that the definition of unstable angina is important in determining the immediate outcome of directional atherectomy. In the absence of rest or postinfarction angina, the immediate results are not significantly different from those obtained in stable angina. Our results also suggest that both the immediate and short-term outcome in unstable angina are not greatly influenced by atherectomy but more so by the pathophysiology of unstable angina, which increases the complications of percutaneous interventions. PMID- 8006283 TI - Dose finding with a novel recombinant plasminogen activator (BM 06.022) in patients with acute myocardial infarction: results of the German Recombinant Plasminogen Activator Study. A study of the Arbeitsgemeinschaft Leitender Kardiologischer Krankenhausarzte (ALKK). AB - OBJECTIVES: The aim of this study was to determine the appropriate dose of a novel recombinant tissue-type plasminogen activator (BM 06.022) for thrombolysis in patients with acute myocardial infarction. BACKGROUND: BM 06.022 is a mutant of tissue-type plasminogen activator expressed in Escherichia coli that can be given as a single bolus because of a prolonged half-life, which might obviate the need for complicated regimens. METHODS: BM 06.022 given as a single bolus was investigated in 142 patients in a multicenter sequential dose-finding study. Efficacy of the drug was assessed from infarct-related artery patency by coronary angiography. RESULTS: With the first dose of 10 MU of BM 06.022, the predefined minimal 90-min patency of 70% was not achieved, as indicated by the sequential probability ratio test after treatment of 42 patients (group A). The second dose of 15 MU of BM 06.022 was given subsequently in the preset maximum of 100 patients (group B). Angiography 30, 60 and 90 min after the bolus injection of BM 06.022 revealed a patent infarct-related artery (Thrombolysis in Myocardial Infarction trial [TIMI] grade 2 or 3) in 65% and 66%, 73% and 74% and 66% and 75% of patients in groups A and B, respectively. Very early reocclusion up to the 90 min angiogram occurred in 17% and 13%, late reocclusion until predischarge angiography occurred in 7% and 5%, and rescue percutaneous transluminal coronary angioplasty after the 90-min angiogram was performed in 6 and 14 patients in groups A and B, respectively. Plasma fibrinogen decreased from 2.79 g/liter (range 0.94 to 4.75) to 1.69 g/liter (range 0.0 to 3.95) in group A and from 2.54 g/liter (range 0.0 to 5.02) to 0.92 g/liter (range 0.0 to 2.68) in group B. Two bleeding complications requiring transfusion or surgical intervention and one nonfatal intracranial hemorrhage were encountered. Eight patients had a reinfarction, and five patients died, all of cardiac causes. CONCLUSIONS: With BM 06.022 given as a single bolus, a high early patency rate of the infarct-related coronary artery can be achieved. The speed of thrombolysis seems to be superior to standard thrombolytic drugs. The compound warrants further evaluation with respect to safety and efficacy by clinical end points. PMID- 8006284 TI - Effects of captopril therapy on endogenous fibrinolysis in men with recent, uncomplicated myocardial infarction. AB - OBJECTIVES: This study investigated the effects of captopril therapy on endogenous fibrinolysis in men with recent, uncomplicated myocardial infarction. BACKGROUND: Angiotensin-converting enzyme inhibitors reduce the incidence of acute coronary syndromes in patients with mild left ventricular dysfunction after myocardial infarction. Abnormal endogenous fibrinolysis, reflected in increased levels of endogenous tissue-type plasminogen activator (t-PA) antigen and plasminogen activator inhibitor type 1 activity, is associated with an increased risk of myocardial infarction in patients with ischemic heart disease. METHODS: In a randomized, double-blind crossover study beginning 8 weeks after uncomplicated myocardial infarction, patients received 4 weeks of placebo and 4 weeks of captopril (75 mg daily) therapy. At the end of each treatment period, we measured t-PA antigen and plasminogen activator inhibitor type 1 antigen and activity. RESULTS: Median values in the 15 patients after placebo and in 12 normal men matched for age and body mass index were, respectively, t-PA antigen 16.0 versus 9.5 ng/ml (p = 0.001), plasminogen activator inhibitor type 1 antigen 17.3 versus 8.6 ng/ml (p = 0.29) and plasminogen activator inhibitor type 1 activity 13.2 versus 6.3 AU/ml (p = 0.04). After 4 weeks of treatment with captopril in the 15 patients, the estimated (95% confidence interval) median reduction in t-PA antigen was 7.3 ng/ml (-4.6 to -10.3 ng/ml, p = 0.001), in plasminogen activator inhibitor type 1 antigen 3.1 ng/ml (+1.5 to -8.4 ng/ml, p = 0.17) and in plasminogen activator inhibitor type 1 activity -2.2 AU/ml (-1.0 to 4.3 AU/ml, p = 0.02). CONCLUSIONS: Treatment with captopril after uncomplicated myocardial infarction is associated with a significant decrease in elevated levels of t-PA antigen and plasminogen activator inhibitor type 1 activity. This may help to explain the reduction in risk of coronary thrombosis associated with the use of angiotensin-converting enzyme inhibitors. PMID- 8006285 TI - Risk stratification for long-term outcome after elective coronary angioplasty: a multivariate analysis of 5,000 patients. AB - OBJECTIVES: We attempted to develop a statistical model to facilitate risk stratification for long-term outcome after elective coronary angioplasty. BACKGROUND: Our understanding of factors related to long-term outcome after coronary angioplasty is limited. Adequate assessment of risk indexes could potentially lead to more appropriate use of percutaneous revascularization. METHODS: We studied 5,000 consecutive patients and assessed 19 clinical and anatomic variables as predictors of long-term event-free survival. Events were defined as death of any cause, myocardial infarction, bypass surgery or repeat percutaneous transluminal coronary angioplasty. Cox proportional hazards models were used to develop an equation for predicting event-free survival in a subset of 4,000 patients. The equation was validated with the remaining 1,000 patients. Variables that were significantly associated with an adverse outcome in the multivariate model included age > 60 years, extent of disease, Canadian Cardiovascular Society functional class, previous coronary angioplasty, male gender, history of diabetes mellitus, history of hypertension and history of congestive heart failure. RESULTS: The statistical model was used to develop a simplified scoring system, and the patients were assigned to three risk subgroups. Event-free survival curves for the three groups were significantly different (p = 0.0001). High risk patients had worse outcomes for each of the end points compared with low and moderate risk patients (p < 0.02). CONCLUSIONS: We demonstrated that clinical and anatomic variables can be used to risk-stratify long-term outcome after angioplasty, that a simplified scoring system can be used for risk stratification and that high risk patients have a low event-free survival. PMID- 8006286 TI - Percutaneous transluminal coronary angioplasty in women compared with men. AB - OBJECTIVES: This study compares in-hospital and long-term outcome after angioplasty in women and men. BACKGROUND: The recognition that coronary artery disease is the most common cause of death in women has increased interest in outcome studies of coronary artery disease in women. METHODS: Patients who had previous coronary revascularization and those who underwent angioplasty in the setting of acute myocardial infarction were excluded. Angioplasty was performed with standard methods. Clinical data were retrieved from a clinical data base and analyzed with standard statistical methods. RESULTS: There were 2,845 women and 7,940 men. The women were older (62 +/- 11 vs. 57 +/- 10 years) and had more hypertension (54.5% vs. 40.1%), diabetes (19.3% vs. 11.7%), grade III to IV angina (71.5% vs. 58.4%) and congestive failure (4.3% vs. 2.1%) than men (all p < 0.0001). More men had a previous myocardial infarction (35.4% vs. 31.0%) and were taller and weighed more (all p < 0.0001). The men had lower ejection fractions and more multivessel disease (31.0% vs. 25.2%) (both p < 0.0001). In women there was a trend toward more Q wave myocardial infarctions (1.1% vs. 0.75%, p = 0.10), and hospital mortality was higher (0.7% vs. 0.1%, p < 0.0001). Angina at follow up was more common in women 40.2% vs. 26.7%, p < 0.0001). The multivariate correlates of in-hospital death were short stature, reduced ejection fraction and multivessel disease, with trends for older age and female gender. Five-year survival was 95% in men and 92% in women (p = 0.0002). However, female gender was not a multivariate correlate of long-term survival and was accounted for by other characteristics, primarily age. The multivariate correlates of long-term survival were older age, congestive failure, reduced ejection fraction, multivessel disease, diabetes, hypertension and a trend for severe angina. No difference between women and men was noted in long-term freedom from myocardial infarction. There were more additional procedures in men than in women. CONCLUSIONS: Despite higher in-hospital mortality, long-term mortality and clinical outcome were similar in both genders when age and body habitus were accounted for. PMID- 8006287 TI - Pulmonary hemorrhage after intracoronary stent placement. AB - OBJECTIVES: The purpose of this study was to determine the incidence and clinical characteristics of pulmonary hemorrhage after intracoronary stent placement. BACKGROUND: Patients undergoing intracoronary stent placement receive intense anticoagulation to prevent stent thrombosis. Pulmonary hemorrhage during intense anticoagulation is uncommon in other clinical settings but has been diagnosed at our institution after stent placement. METHODS: The clinical records of 88 consecutive patients undergoing intracoronary stent placement at a single tertiary referral center were reviewed for evidence of pulmonary hemorrhage. The diagnosis of pulmonary hemorrhage required bronchoscopic demonstration of fresh blood or thrombus in the airways of patients with sudden onset of hemoptysis, dyspnea or hypoxemia and new pulmonary infiltrates on chest radiograph. RESULTS: Pulmonary hemorrhage was identified in 4 (4.5%) of 88 patients undergoing intracoronary stent placement. Patients commonly presented with dyspnea, hemoptysis, hypoxemia, new pulmonary infiltrates on chest radiograph and excessive prolongation of the activated partial thromboplastin time. Mean onset of symptoms was 31.5 h after the procedure. Three of four patients were treated for presumed cardiogenic pulmonary edema until invasive hemodynamic monitoring revealed normal left ventricular filling pressures. Pulmonary hemorrhage resulted in prolonged admissions in the intensive care unit and hospital. One patient died. CONCLUSIONS: Pulmonary hemorrhage after coronary stent placement was commonly misdiagnosed and was associated with significant morbidity and mortality in our patients. Although its mechanism is unclear, excessive anticoagulation was a likely contributing factor. Clinical trials comparing varying strategies and intensities of anticoagulation may be indicated. PMID- 8006289 TI - The case for vitamin supplementation. PMID- 8006288 TI - Estimated contribution of coronary artery bypass graft surgery to the decline in coronary heart disease mortality: the Minnesota Heart Survey. AB - OBJECTIVES: This study assessed the possible contribution of coronary artery bypass graft surgery to the decline in coronary heart disease mortality in the Minneapolis-St. Paul metropolitan area population between 1970 and 1984. BACKGROUND: Coronary artery bypass graft surgery is a major contemporary therapeutic approach for coronary heart disease. Its use has increased over the past two decades because it provides relief of symptoms and, in certain circumstances, prolongs life. During the period that age-adjusted coronary heart disease mortality has decreased, the use of coronary artery bypass graft surgery has increased dramatically, suggesting a relation. METHODS: All 30- to 74-year old Minneapolis-St. Paul area residents undergoing coronary artery bypass graft surgery between 1970 and 1984 (9,548 patients) were registered; their medical records were abstracted; and their survival was ascertained. These data were used in a medical survival probability model using a multivariate analytical approach developed from registries of patients treated medically. The model assumed that coronary artery bypass graft surgery was not available. Two annual mortality rates were compared: the observed Minneapolis-St. Paul annual coronary heart disease mortality rate and the modeled annual coronary heart disease mortality rate. The difference between these rates was the estimated contribution of coronary artery bypass graft surgery to the decline in coronary heart disease mortality rates. RESULTS: Between 1970 and 1984, the estimated surgical contribution increased from 0.2% (increased mortality) to +6.6% of the annual decrease in Minneapolis-St. Paul coronary heart disease mortality. CONCLUSIONS: Between 1970 and 1984, the contribution of coronary artery bypass graft surgery to the decline in coronary heart disease mortality, although small, gradually increased. This change appeared to be related to an increased frequency of coronary artery bypass graft surgery, improved operative mortality and changes in the clinical mix of surgical patients. PMID- 8006290 TI - To supplement or not to supplement: is it a question? PMID- 8006291 TI - Magnesium, antioxidants and myocardial infarction. PMID- 8006292 TI - Vitamin supplements: current controversies. AB - Supplemental use of vitamins to prevent disease constitutes a major commercial enterprise in the United States. The efficacy of such use, or even the need for intakes above that which can be supplied by means of diet alone, has been the source of considerable controversy in the medical and scientific fields. Recently published data have given strong support to several of the claims for major benefits of disease prevention, including that of cancer, cardiovascular disease, carpal tunnel syndrome, and neural tube defects, to name just a few. The purported benefits for supplemental vitamin usage are discussed for these diseases, along with a call for a re-evaluation of the underlying philosophy of the Recommended Dietary Allowances, or consideration of their abolition, based on newly emerging data. PMID- 8006293 TI - A review of magnesium, acute myocardial infarction and arrhythmia. AB - Many years ago, experimental medicine accumulated substantial evidence that magnesium (Mg) balance was important for a stable cardiovascular system. Recent clinical interest was aroused by evidence of decreased mortality in patients with acute myocardial infarction (AMI), treated with Mg infusions. Pharmacologic actions of Mg include its antiarrhythmic, antivasospastic and other important cardiovascular effects, substantiating the rationale for its use in AMI. Direct pharmacologic effect of this ion, rather than compensation of hypomagnesemia frequently encountered during acute ischemic injury, has been suggested to account for the above benefits. Several trials studied the efficacy of early Mg therapy in decreasing mortality from AMI while most of the data point to improved survival, a few trials could not demonstrate any benefit of Mg. The reported rate of complications with this therapy is low though the potential for serious side effects exists. Larger studies of Mg in AMI are expected to resolve the existing controversy. PMID- 8006294 TI - Nutrition aspects of continuous ambulatory peritoneal dialysis: a review. AB - Continuous ambulatory peritoneal dialysis (CAPD) is an increasingly popular alternative to hemodialysis. Nutrition practitioners in the in- and outpatient setting must be knowledgeable about specific nutritional considerations in these patients. In this paper, we briefly review factors which play a role in the malnutrition often encountered in end-stage renal disease, and focus on metabolic abnormalities, nutritional requirements, and nutritional assessment of patients undergoing CAPD. Urea kinetic modeling as an adjunct to nutritional assessment is explained in detail. PMID- 8006296 TI - Glycolysis abnormalities in fibromyalgia. AB - OBJECTIVE: Primary fibromyalgia (FM) is a painful condition, generally treated by analgesic drugs and antidepressants, which has been associated with hyperpyruvicemia and reduced high energy phosphate in muscle. Biological investigations were performed in patients with FM to determine whether this syndrome was related to carbohydrate metabolism impairment. METHOD: Glycolysis was studied in 25 patients with FM, 10 patients with hypothyroidism (HO), 15 patients with osteoarticular chronic pain (OACP), and 36 healthy controls. Laboratory studies were performed on whole blood (pyruvate), erythrocytes (pyruvate kinase, 2-3 diphosphoglycerate, glyceraldehyde phosphodeshydrogenase, adenosine triphosphate), plasma and serum (lactate at rest and after forearm ischemic exercise, lactico deshydrogenase iso-enzymes). RESULTS: Comparisons between study groups and controls demonstrated increased pyruvate and decreased lactate production in FM and HO; adenosine triphosphate and muscular isoenzymes of lacticodeshydrogenase were decreased in FM only; glycolysis was not significantly impaired in OACP. CONCLUSIONS: These findings provide support that FM is associated with biochemical abnormalities which require appropriate metabolic therapy. PMID- 8006295 TI - Dietary and serum magnesium levels in patients with acute myocardial infarction, coronary artery disease and noncardiac diagnoses. AB - OBJECTIVE: To study the relation of dietary and serum levels of magnesium (Mg) in acute myocardial infarction (AMI) and its complications in relation to noncardiac diagnoses. METHODOLOGY: Case control study in a primary and secondary care center for AMI patients. The study included 460 subjects with definite AMI (n = 335, group A), possible AMI (n = 64, group B), unstable angina (n = 19, group C) and controls with noncardiac chest pain (n = 42, group D). Demographic variables, dietary intake, and clinical and biochemical data were compared. Mean age, sex, body weight, and body mass index were comparable in all the groups. RESULTS: Dietary fat and cholesterol intakes were significantly higher and carbohydrate intakes were lower in group A, B and C patients with coronary artery disease compared to control group D. Dietary consumption of Mg was comparable in all groups; however, in 85 patients in group A (272.5 mg/day) and 17 in group B (280.4 mg/day) in whom ventricular arrhythmias were present, Mg intake was relatively lower compared to control group D (316.6 mg/day). Serum Mg levels in group A (1.66 mEq/L), B (1.65 mEq/L), and C (1.66 mEq/L) were within normal (1.74 mEq/L) limits, but were significantly lower than in control group D. CONCLUSIONS: Lower serum Mg in group A, B and C patients was attributed to increased demand during AMI, although in patients with complications (ventricular arrhythmias), Mg deficiency may in part result from relatively lower Mg intake, a hypothesis which requires further study. PMID- 8006297 TI - Zinc status of a group of pregnant adolescents at 36 weeks gestation living in southern Ontario. AB - OBJECTIVE: Pregnant adolescents have very high zinc (Zn) requirements to support the developing fetus and to maintain skeletal maturation after menarche. METHODS: Sixty-six adolescents aged 17.1 +/- 0.15 years (mean +/- SEM; range 14.5-19.0 years) were recruited from three regions of Southern Ontario at 35.9 +/- 0.15 weeks gestation. Data on sociodemographic status, health, infant birth weight and birth length, smoking, alcohol consumption, and prenatal supplement use were collected. Fasting venipuncture blood was analyzed for Zn (via AAS) and alkaline phosphatase in plasma; scalp hair was analyzed for Zn by instrumental neutron activation. RESULTS: Mean (95% CI) values were: plasma Zn 10.7 (10.0-11.5) mumol/L; plasma alkaline phosphatase 46.6 (43.7-49.5) U/L; hair Zn 2.64 (2.52 2.77) mumol/g. None of the plasma and hair Zn values were indicative of suboptimal Zn status. Mean plasma Zn concentrations of subjects (n = 19) consuming a supplement with Zn sulfate were higher than those of subjects consuming a supplement with Zn oxide (n = 18) (12.2 vs 9.7 mumol/L; p < 0.02) and unsupplemented subjects (n = 11) (9.4 mumol/L). Plasma Zn concentrations correlated negatively with reported birth lengths (mean +/- SEM = 51.6 +/- 0.31 cm) while accounting for chronological age (r = 0.42; p < 0.01), but not with reported birth weights (mean +/- SEM = 3.439 +/- 0.107 kg). CONCLUSIONS: Results emphasize that the form of Zn must be taken into account when considering the impact of prenatal supplements containing Zn on plasma Zn concentrations. Suboptimal Zn status was not prevalent in these pregnant adolescents. PMID- 8006298 TI - Correlates of blood pressure in Seventh-Day Adventist (SDA) and non-SDA adolescents. AB - OBJECTIVE: This comparative study was designed to discover early determinants of systolic (S) and diastolic (D) blood pressure (BP) elevations in 138 Seventh-Day Adventist (SDA) and 89 non-SDA male and female adolescents (median age, 17 years) living at three residential secondary schools in North Carolina. METHODS: Measurements were made of blood pressure, body weight, and height, and information was collected on lifestyle factors, dietary intake, and other behaviors, including exercise, religiosity, Type A behavior, and anger, by questionnaire. Multiple stepwise regression analyses were performed with BP, either SBP or DBP, as the independent variable. RESULTS: A significant direct association was found only between body weight and BP, but weak associations were shown between BP and other variables, including exercise, diet, religiosity, Type A behavior, and anger. Male and female SDA students showed significantly higher SBPs and DBPs than did non-SDA adolescents though the differences were small (approximately 5 mm for each sex). CONCLUSIONS: These findings suggest that the higher BP values of SDA adolescents, who were all practicing lacto-ovo vegetarians, compared to similarly aged health-conscious non-SDAs, are determined more by eating behaviors that contribute to gains in body weight than by any other lifestyle variable. Furthermore, these data support the notion that the BP protective effects of the vegetarian diet may not emerge in these SDA youth until early adulthood. PMID- 8006299 TI - Requirements for biotin are not affected by the combination of copper deficiency and fructose feeding. AB - OBJECTIVE: The objective of the present study was to establish whether copper (Cu)-deficient rats fed a diet containing fructose as their sole carbohydrate source require more biotin than the recommended 2 mg/kg diet when egg-white serves as the dietary protein. METHODS: Eighty weanling male Sprague-Dawley rats were randomly divided into 8 groups according to type of dietary carbohydrate (starch or fructose), level of Cu (0.6 micrograms Cu/g diet or 6.0 micrograms Cu/g diet) and level of biotin (2 mg/kg diet or 10 mg/kg diet). RESULTS: Regardless of the level of dietary biotin, Cu-deficient rats fed a fructose containing diet exhibited growth retardation, anemia, atrophied pancreata, enlarged hearts and similar death rates. The remaining Cu-deficient rats fed fructose were emaciated and sick regardless of dietary biotin levels. The concentration of biotin in serum and biotin content of liver of rats fed fructose were higher than corresponding values from rats fed starch. CONCLUSION: Cu deficient rats fed fructose are not deficient in biotin compared to published normal values. Supplementation of 10 mg/biotin/kg diet did not improve morbidity or mortality and therefore was not beneficial. PMID- 8006300 TI - Bread as a source of salt: an international comparison. AB - OBJECTIVE: The salt (NaCl) content of bread, obtained from Belgium and 25 other regions or countries worldwide, was analyzed to evaluate the importance of bread as a source of dietary salt in a population. METHODS: A total of 1166 dried bread samples were analyzed using a hot HCl extraction technique followed by flame photometry and performed by the same laboratory technician in Leuven (Belgium); 534 samples from Leuven were analyzed over 10 time periods from 1967-73 to 1992 together with 562 samples from 11 other European countries, 44 from the United States and Peru, and 26 from Asia. RESULTS: The average mean salt content of fresh bread (= dried bread times 0.6) in European countries was 12.4 +/- 1.7 g/kg for white and 13 +/- 1.0 g/kg for brown bread. In Japan and Korea it was about 8.5 g/kg and in Pakistan, Thailand, Nepal, and Laos about 5 g/kg. The mean sodium/potassium ratio with Na and K in mmol was 8.0 for white and 4.5 for brown bread, much higher than the recommended value of 1.0. Bread with a very low salt content was found in certain areas of Peru, Spain, and Italy. CONCLUSION: The overall salt content of bread in Western countries is excessive, and a gradual reduction is highly desirable. PMID- 8006301 TI - Insulin-like growth factor I as an indicator of protein-energy undernutrition among metabolically stable hospitalized elderly. AB - OBJECTIVE: The primary objective of this cross-sectional study was to test the hypothesis that the plasma concentration of insulin-like growth factor I (IGF-I) correlates with the risk of in-hospital morbidity among metabolically stable elderly. The secondary objective was to determine whether IGF-I correlates with other putative indicators of protein-energy nutritional status. SUBJECTS: To meet these objectives, 110 randomly selected admissions to a Geriatric Rehabilitation Unit (GRU) of a Veterans Administration hospital were studied. The average age of the study patients was 76 years; 98% were male, and 78% were white. OUTCOME MEASURES: At admission, each patient completed a comprehensive medical, functional, neuropsychological, and nutritional assessment including the attainment of a plasma IGF-I determination. While in the hospital, each subject was monitored daily for development of complications. RESULTS: Subsequent to GRU admission, 44 patients (40%) experienced at least one complication; 36 patients (33%) experienced an infectious complication, 8 patients (7%) experienced a life threatening complication, and 5 patients (5%) experienced a life-threatening infectious complication. There was no correlation between IGF-I and development of a non-life-threatening complication ("any complication" or "any infectious complication"). However, IGF-I was a strong predictor of "life-threatening" and "life-threatening infectious" complications. The logistic regression model incorporating the independent variable IGF-I differentiated the patients who would develop a "life-threatening" complication from those who would not with a sensitivity of 75%, a specificity of 76%, and an overall predictive accuracy of 76%. IGF-I was highly correlated with admission serum albumin, transferrin, and cholesterol, triceps skinfold thickness, body weight expressed as a percent of ideal, and body mass index. There was no correlation between IGF-I and the Katz Index of Activities of Daily Living score, age, or anergy status. CONCLUSION: IGF I is a strong predictor of "life-threatening" and "life-threatening infectious" complications and may be a clinically useful marker for protein-energy undernutrition among metabolically stable hospitalized elderly patients. PMID- 8006302 TI - Drinking water as an iron carrier to control anemia in preschool children in a day-care center. AB - OBJECTIVE: Several foods have been used as iron (Fe) carriers to fight widespread global Fe deficiency and anemia. This paper describes the longitudinal effect of Fe-fortified drinking water given to a group of Brazilian preschool children. DESIGN: The experimental design included 31 preschool children who attended a day care institution. Hemoglobin and serum ferritin were the blood parameters used to check the Fe status. Fe++ sulfate (20 mg Fe/L) was added daily to their drinking water container and measurements were obtained before the addition, 4 and 8 months later. RESULTS: The number of Fe-deficient children decreased drastically after they started drinking the Fe-enriched water. Mean hemoglobin values increased from 10.6 to 13.7 g/dL and serum ferritin from 13.7 to 25.6 micrograms/L. There were no problems related to the salt addition or to the children drinking the Fe-enriched water. CONCLUSION: Fe-enriched drinking water was shown to be a practical alternative to supply Fe to children attending a day care institution. PMID- 8006303 TI - Case report: failure to thrive in a breast-fed infant is associated with maternal dietary protein and energy restriction. AB - OBJECTIVE: To determine whether failure to thrive in a breast-fed infant could be attributed to altered milk production or composition from a mother who consumed a self-imposed energy- and protein-restricted diet. DESIGN: We evaluated the changes in growth and body composition, dietary intakes, and milk production and composition in a mother-infant pair throughout the first postpartum year. SETTING: The Children's Nutrition Research Center Metabolic Research Unit. SUBJECTS: A breast-feeding mother-infant pair. MEASURES OF OUTCOME: Body composition was measured by total body electrical conductance, dietary intakes by food records, milk production by the test weighing procedure, and milk composition by proximate analyses. RESULTS: A marked decline in the infant's linear and ponderal growth rates occurred when the mother consumed an energy- (20 kcal.kg-1.d-1) and protein- (0.7 g.kg-1.d-1) restricted diet. The retardation in body weight gain was associated with an arrest of body fat, but not lean body mass, accretion. Maternal milk production showed positive relationships with maternal dietary energy (p < 0.01, r = 0.93) and protein (p < 0.05, r = 0.83) intakes. Milk composition reflected changes consistent with those of weaning rather than a sequela of the mother's diet. CONCLUSIONS: We concluded that failure to thrive in a breast-fed infant could be attributed to reduced milk production in conjunction with maternal dietary energy- and protein-restriction and that an assessment of maternal dietary intakes is essential in an evaluation of the breast-fed infant with failure to thrive. PMID- 8006304 TI - Desensitization to trimethoprim/sulfamethoxazole in HIV-infected patients. AB - BACKGROUND: Trimethoprim-sulfamethoxazole (T/S) is an effective and important prophylactic medication for HIV-infected patients that must frequently be discontinued because of allergic reactions. OBJECTIVE: Our objective was to assess the safety, the frequency of success, and the duration of desensitization to T/S in HIV-infected patients. METHOD: We studied oral desensitization with T/S of patients with a history of allergy to the medication and longitudinal follow up. Twenty-eight men with a history of T/S-induced skin rashes were studied. Mean age was 35 years (range, 26 to 50 years). Mean CD4 count was 89 cells/mm3 (range, 0/mm3 to 210/mm3). Patients were seen every 4 to 6 weeks. Mean follow-up was 19.07 weeks (range 2 to 81 weeks). RESULTS: After 32 weeks, 23 of 28 (82%) patients were successfully desensitized (four had rashes develop, and one could not continue for personal reasons). Of the 23 patients who were successfully desensitized, six were known to have subsequently discontinued T/S (four had rashes; two discontinued on the advice of their personal primary physicians). Six patients were lost to follow-up. One patient died of pulmonary Kaposi's sarcoma. Ten patients are taking the medication regularly without any problems. CONCLUSION: T/S desensitization is a simple, safe and effective means to provide it for most patients with a history of "allergic" rashes. PMID- 8006305 TI - Glucocorticoids suppressed production and gene expression of interleukin-5 by peripheral blood mononuclear cells in atopic patients and normal subjects. AB - BACKGROUND: Interleukin-5 (IL-5) is known to play a major role in regulating eosinophil function in atopic diseases, including bronchial asthma. Glucocorticoids are most effective agents for treating these diseases. However, their mechanism remains unclear. We examined the effects of glucocorticoids on the production and gene expression of IL-5 in atopic patients and normal subjects. METHODS: Human peripheral blood mononuclear cells (PBMCs) in five atopic and four normal subjects were cultured with phytohemagglutinin and phorbol 12-myristate 13-acetate (PMA) in the presence of dexamethasone. IL-5 secreted by PBMCs was assayed by ELISA. Gene expression of IL-5 by PBMCs was assessed semiquantitatively by sequential reverse transcription-polymerase chain reaction, and Southern blot analysis. RESULTS: Phytohemagglutinin/PMA-stimulated PBMCs from all atopic patients and three normal subjects secreted detectable amounts of IL 5, which were suppressed by dexamethasone in a dose-dependent manner, with 85.8% suppression at 10(-6) mol/L. Gene expression of IL-5 was detected by reverse transcription polymerase chain reaction in PBMCs from all subjects, even when not stimulated; was increased by stimulation; and was suppressed by dexamethasone. The concentration of dexamethasone resulting in 50% inhibition in IL-5 gene expression did not differ between atopic patients and normal subjects. CONCLUSION: These findings indicate that dexamethasone suppressed IL-5 production in atopic human PBMCs through an inhibitory action on the gene expression. These results suggest that the suppression of IL-5 production through the suppression of IL-5 gene expression is one of the most important mechanisms by which glucocorticoids inhibit eosinophil functions in the treatment of atopic diseases, including bronchial asthma. PMID- 8006306 TI - Particulate Aspergillus fumigatus antigens elicit a TH2 response in BALB/c mice. AB - BACKGROUND: In order to understand the immunoregulation in allergic aspergillosis, a murine model was developed by exposing animals to particulate and soluble antigens of Aspergillus fumigatus. METHODS: BALB/c mice were exposed to soluble Aspergillus antigen intranasally. Animals showing moderate levels of IgE were subsequently exposed to soluble antigen or antigen conjugated to polystyrene beads intranasally. The IgE and IgG1 in the sera and the eosinophils in the blood and lungs were studied. The spleen and lung mononuclear cells were stimulated with both concanavalin A and antigen and evaluated for production of interleukin (IL)-4, IL-5, IL-10, and interferon-gamma. RESULTS: Animals exposed to particulate antigens showed more elevated serum IgE levels and increased numbers of eosinophils in the blood and lungs than those exposed to soluble antigen. Lung cell cultures from animals exposed to particulate antigens when stimulated with Aspergillus produced IL-4 and IL-5, indicating a TH2 type of response. Animals exposed to soluble antigens showed a weaker TH2 response, as evidence by low IgE levels in sera, fewer eosinophils in the blood, and low levels of cytokine production from lung and spleen cells. CONCLUSION: The results indicate that the physical nature of the antigen may have a major role in determining the type of immune response of the host. PMID- 8006307 TI - Relationships among allergen-induced early and late phase airway obstructions, bronchial hyperreactivity, and inflammation in conscious, unrestrained guinea pigs. AB - The relationship among allergen-induced early asthmatic reactions (EARs) and late asthmatic reactions (LARs), early (between EAR and LAR) and late (after LAR) changes in bronchial reactivity to histamine and infiltration of inflammatory cells into the airways were investigated with a new model of chronically instrumented, unrestrained, and ovalbumin-sensitized guinea pigs. Two different provocation strategies were examined. With the use of stepwise increasing allergen concentrations, all 21 animals responded with an EAR, which in 15 animals (71%) was followed by an LAR. By inhalation of a single allergen concentration for up to 15 minutes, 11 of 14 animals showed an EAR, which in 10 animals (71%) was followed by an LAR. One animal did not respond, whereas the remaining two showed only an LAR. At 6 hours (after the EAR) and 24 hours (after the LAR) after allergen provocation, a significant bronchial hyperreactivity (BHR) toward histamine aerosol was observed in the dual responding animals (both protocols), but not significant changes were observed in animals with a single EAR or a single LAR. Significant correlations were found between the initial increase in airway obstruction after allergen provocation and the severity of the EAR and LAR, as well as the early and late BHR; in addition, a significant correlation was found between the early and late BHR. In contrast, the severity of the LAR did not correlate with the BHR at 6 hours and 24 hours. At 6 hours, there was a marked tendency to an increase in the number of eosinophils and a significant increase in the number of neutrophils in the bronchoalveolar lavage. At 24 hours after provocation, the number of eosinophils and neutrophils was significantly enhanced. These data suggest that early activation of mast cells and/or inflammatory leukocytes may determine the development of the LAR, as well as the early and late BHR, although there appears to be no causal relationship between the BHR at both time points and the severity of the LAR. The relationships among allergen-induced EAR and LAR, early and late BHR, and airway inflammation observed in this new guinea pig model are strikingly similar to those observed in patients with asthma. PMID- 8006308 TI - Analysis of cellular and biochemical constituents of induced sputum after allergen challenge: a method for studying allergic airway inflammation. AB - To determine whether analysis of the constituents of induced sputum permits detection of changes provoked by aerosolized antigen challenge, we performed sputum induction (20-minute inhalation of aerosolized 3% saline solution) before and after aerosolized allergen challenge in eight subjects with asthma. Total cell counts and cell differentials of nonsquamous cells in induced sputum samples were determined after the samples were homogenized in dithiothreitol. Centrifugation of the entire homogenized sputum sample yielded supernatant that could be analyzed for biochemical constituents. We found that the median percentage of eosinophils and neutrophils in induced sputum samples was significantly higher 4 hours after allergen challenge neutrophils in induced sputum samples was significantly higher 4 hours after allergen challenge than at baseline (12% vs 0.5%, p < 0.05; 30.5% vs 7.5%, p < 0.05) and remained high 24 hours after challenge. Median levels of eosinophil cationic protein and histamine in induced sputum supernatants were significantly higher 4 hours after challenge than at baseline (151.3 vs 39.8 ng/ml, p < 0.05; 19.4 vs 8.8 micrograms, p < 0.05) and remained significantly higher 24 hours after challenge. Tryptase was detectable in sputum from seven of the subjects, and in these subjects, we found a trend toward an increase in median tryptase levels 4 hours after allergen challenge (4.4 vs 2.2 U/L, p = 0.09). We conclude that analysis of induced sputum after aerosolized allergen challenge reveals changes in inflammatory cells and markers similar to those reported in bronchoalveolar lavage fluid and that sputum induction is a useful noninvasive method for studying allergic airway inflammation in asthma. PMID- 8006309 TI - Allergenicity and antigenicity of chicken egg ovomucoid (Gal d III) compared with ovalbumin (Gal d I) in children with egg allergy and in mice. AB - When attempting to generate mouse monoclonal antibodies to hen's egg ovalbumin, injection of commercially purified ovalbumin resulted in monoclonal antibodies, which when assayed against commercially purified ovalbumin (Gal d I) or ovomucoid (Gal d III), appeared to be specific to both. With the use of high-performance liquid chromatography (HPLC)-repurified ovalbumin and ovomucoid in assay procedures, monoclonal antibodies generated by commercially purified ovalbumin were found to be specific for ovomucoid only. To clarify this phenomenon, mice were serially injected with commercially purified ovalbumin or HPLC-repurified ovalbumin. It was found that most of the antibody response to commercially purified ovalbumin was directed against the minor (< 1%) ovomucoid contaminant and that HPLC-repurified ovalbumin failed to produce antibodies to ovomucoid. Commercially purified ovomucoid resulted in only minimal amounts of antibodies to ovalbumin. Thus when commercially purified ovalbumin is used both for immunization and immunoassay, most of the antibodies produced are actually against the small amount of ovomucoid contaminant, and not ovalbumin. To determine whether ovomucoid is the major antigenic and allergenic egg white protein in human beings, one group of 18 children with egg allergy were skin prick tested with half-log dilutions of egg white extract and diethylaminoethyl cellulose (DEAE)-repurified ovomucoid, ovalbumin, and lysozyme. Ovomucoid mean wheal diameters were significantly greater than wheal diameters in response to ovalbumin, lysozyme, and egg white extract at the three most concentrated of five dilutions tested: 0.01, 0.03, and 0.1 mg/ml (p < 0.01). Serum ovomucoid-specific IgE and IgG antibody concentrations to DEAE-repurified ovomucoid were significantly greater than that to DEAE-repurified ovalbumin (p < 0.05). In a second study, 10 patients with egg allergy and persistent egg hypersensitivity were compared with 11 patients with egg allergy in whom clinical tolerance to egg developed. IgE antibodies to repurified ovomucoid were significantly greater in patients with persistent egg hypersensitivity compared with patients in whom clinical tolerance developed at the time of both initial and follow-up food challenges. In contrast, there were no significant differences in IgE antibody concentrations to repurified ovalbumin in either group at any time. These results suggest that ovomucoid is the immunodominant protein fraction in egg white and that the use of commercially purified ovalbumin has led to an overestimation of the dominance of ovalbumin as a major egg allergen and antigen in human beings. PMID- 8006310 TI - Synthesis of interleukin-1 alpha, interleukin-6, and interleukin-8 by cultured human nasal epithelial cells. AB - Nasal epithelium forms the initial barrier between the environment and the respiratory system and may be a potential source of proinflammatory interleukins, which contribute to the pathophysiology of allergic and nonallergic rhinitis. To explore this possibility, epithelium and cultured human nasal epithelial cells from nasal turbinates of patients undergoing surgery for treatment of upper airway obstruction were examined for the spontaneous expression of interleukin (IL)-1 alpha, IL-1 beta, IL-6, and IL-8. Human nasal epithelial cell lysates and culture supernatants were assayed by two-site ELISAs specific for IL-1 alpha, IL 1 beta, IL-6, or IL-8. Maximum concentrations of these cytokines in supernatants ranged from approximately 0.2 to 2 ng/ml for IL-1 alpha, 1.5 to 7 ng/ml for IL-6, and 100 to 3000 ng/ml for IL-8. IL-1 alpha was predominantly cell-associated, whereas most of the IL-8 and all of the IL-6 were detected in the supernatant. Little or no IL-1 beta was detected by ELISA in the supernatants or cell lysates. Whole tissue turbinates and isolated epithelium were also examined for IL-1 beta, IL-6, and IL-8 mRNA expression by Northern blot analysis. IL-6 and IL-8 mRNAs were detected, whereas IL-1 beta mRNA was not. Furthermore, IL-6 and IL-8 release from human nasal epithelial cell cultures was enhanced by addition to the cultures of lipopolysaccharide, and IL-6 release was inhibited by polymyxin B. Thus human nasal epithelium may be a major source of IL-1 alpha, IL-6, and IL-8 in allergic and nonallergic rhinitis. Production of those proinflammatory cytokines by epithelial cells of the nasal and sinus mucosa may contribute to the pathologic and clinical events that occur in these diseases. PMID- 8006311 TI - Skin testing with natural foods in patients suspected of having food allergies: is it a necessity? PMID- 8006312 TI - Urinary retention as a result of administration of terfenadine. PMID- 8006313 TI - Direct exposure of carpets to sunlight can kill all mites. PMID- 8006314 TI - Systemic reactions to intravenous iron therapy in patients receiving angiotensin converting enzyme inhibitor. PMID- 8006315 TI - Elevated production of interleukin-4 and interleukin-5 by T cells in a child with idiopathic hypereosinophilic syndrome. PMID- 8006316 TI - Multiple chemical sensitivity or multi-organ dysesthesia. PMID- 8006317 TI - A training program directors' committee report: topics related to controversial practices that should be taught in an allergy and immunology training program. AAAI Training Program Directors' Committee. American Academy of Allergy and Immunology. PMID- 8006319 TI - Biphasic systemic anaphylaxis: an inpatient and outpatient study. AB - We attempted to ascertain the incidence of systemic biphasic anaphylactic reactions in both outpatients and inpatients. Madigan Army Medical Center is a large teaching facility. The Allergy Clinic staff sees approximately 20,000 patients per year, and an average of 27,000 allergy immunotherapy injections are administered each year. During the years 1988 to 1991 we collected data from a total of 35 patients who had experienced, during the 30-minute waiting period in the clinic, symptoms and signs consistent with anaphylaxis. A total of 44 anaphylactic reactions were noted, with only two (5%) involving a biphasic systemic pattern. All patients were observed and treated within the clinic until symptoms and signs had resolved. None of the patients were treated with or were presently using glucocorticosteroids during the time of their reactions. Of the reactions noted, 25 (57%) involved only cutaneous manifestations of anaphylaxis, three (7%) involved the laryngeal/upper airway area, eight (18%) involved bronchospasm alone, three (7%) involved the rhinoconjunctivae, and five (11%) involved more than one site or type. None of the patients experienced any symptoms or signs of cardiovascular compromise or collapse after allergy extract injections. During the years 1986 to 1992 a total of 59 patients were admitted to the medical ward or intensive care unit with the diagnosis of systemic anaphylaxis. Of 59 patients, four (7%) experienced a recurrent (biphasic) anaphylactic reaction without reexposure to the initial inciting agent. The remaining 55 patients (93%) did not experience any further systemic anaphylaxis after initial hospital admission and treatment. Two of the patients with biphasic anaphylaxis were first seen with hypotension and generalized urticaria.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8006318 TI - A meta-analysis of the effect of oral and inhaled corticosteroids on growth. AB - This analysis summarizes studies comparing attained heights with expected heights of children with asthma treated with inhaled or oral corticosteroids. The possible moderating effects of treatment duration, and dosage and asthma severity are also examined. A preliminary database of 95 articles rendered 21 includable studies representing 810 patients with asthma, which yielded 29 tests of the corticosteroid-growth effect. Statistical integration of the results of these studies revealed a significant but small tendency for corticosteroid therapy in general to be associated with diminished final height (Z = 2.328, p = 0.01, mean r = -0.023). However, this effect varied for the specific drugs under consideration. As expected, significant weak growth impairment was observed for prednisone (Z = 2.137, p = 0.0164, mean r = -0.295) and "other oral corticosteroids" (Z = 9.107, p = 2.44E-18, mean r = -0.260). On the other hand, a significant moderate tendency was observed for inhaled beclomethansone dipropionate therapy to be associated with attaining normal stature (Z = 7.395, p = 2.17E-13, mean r = +0.432). There was no statistical evidence for beclomethasone dipropionate therapy to be associated with growth impairment at higher doses, for longer therapy durations, or among patients with more severe asthma. This meta-analytic integration indicates that available studies of inhaled beclomethasone dipropionate therapy do not show an association between its use and the adverse effect of diminished stature. PMID- 8006320 TI - Control of airborne latex by use of powder-free latex gloves. AB - OBJECTIVE: Our objective was to assess airborne latex allergen exposure in the workplace of a hospital laboratory technician with occupational latex sensitization and repeated anaphylactic episodes from this. Her allergic manifestations had cleared only when coworkers changed to powder-free latex gloves. Therefore a laboratory still using powdered latex gloves was selected for comparative airborne latex sampling. DESIGN: The design was a survey. SETTING: We used a hospital hematology laboratory, and a biochemistry laboratory was used for comparison. PARTICIPANTS: The index case with latex allergy is described. An average of 10 employees worked on the day shift in the same laboratory, and 10 employees worked in the biochemistry laboratory studied. MAIN OUTCOME MEASURE: Airborne latex allergen levels obtained by high airflow area sampling were compared in the laboratory using powder-free latex gloves and in the laboratory using powdered latex gloves. RESULTS: Levels were below the level of detection (< 0.02 ng/m3 of latex allergen) in the laboratory using powder-free latex gloves but ranged from 39 to 311 ng/m3 in the laboratory using powdered gloves. CONCLUSIONS: Airborne latex allergen is produced with use of powdered latex gloves. Such usage by coworkers may provoke respiratory and anaphylactic response to latex in sensitized subjects. Use of powder-free gloves by coworkers may enable such patients to continue work in their trained profession and may prevent measurable airborne latex exposure. Affected patients, however, still need to avoid direct latex contact. PMID- 8006321 TI - Banana allergy in patients with immediate-type hypersensitivity to natural rubber latex: characterization of cross-reacting antibodies and allergens. AB - BACKGROUND: An association between allergy to latex and banana has been reported. Even though cross-reacting IgE antibodies have been demonstrated, in no study has the existence of structurally similar allergens been confirmed. In the present study banana allergy was studied in a large series of patients with latex allergy. Specific IgE antibodies were characterized for cross-reactivity and compared with pollen RAST results. Latex and banana extracts were investigated for common antigens and allergens. METHODS: Latex-, banana-, and pollen-specific (birch, timothy, mugwort) IgE were measured in 47 sera from patients with latex allergy. Thirty-one patients were skin prick tested with banana and questioned for possible reactions after eating bananas. Several RAST inhibition and immunospot inhibition studies were used to characterize cross-reacting IgE antibodies. Structurally similar antigens and allergens were evaluated with crossed-line immunoelectrophoresis and crossed-line radioimmunoelectrophoresis, respectively. RESULTS: Latex RAST results were positive in 31 (66%) and banana RAST results were positive in 26 (55%) of the 47 sera. Of the 31 latex RAST positive sera, 25 (81%) were also banana RAST-positive. Results from latex RAST correlated significantly with results from banana RAST (p < 0.001), but not with those from pollen RAST (p > 0.05). Banana skin prick test results were positive in 11 (35%) of the 31 patients tested. Symptoms after eating bananas were reported by 16 (52%) of the 31 patients. In inhibition studies the binding of IgE antibodies to solid-phase banana and to several latex preparations was inhibited by latex and banana, respectively. In crossed-line immunoelectrophoresis at least one antigen from banana fused with an antigen from latex, which also bound IgE antibodies in autoradiography (crossed-line radioimmunoelectrophoresis). CONCLUSIONS: Patients with latex allergy have symptoms caused by banana and show positive skin test and specific IgE test results. Cross-reacting IgE antibodies were confirmed by several inhibition techniques. For the first time, a structurally similar antigen/allergen was demonstrated. PMID- 8006322 TI - Deliberate bee sting challenge of patients receiving maintenance venom immunotherapy at 3-month intervals. AB - BACKGROUND: A large part of the cost and inconvenience associated with venom immunotherapy (VIT) is related to the need for monthly treatments. Since VIT is advocated for at least 3 to 5 years, and occasionally longer, reducing the number of venom injections may cut down significantly on both cost and inconvenience. OBJECTIVE: We evaluated whether maintenance VIT given every 3 months is both safe and effective regarding reactions to treatment injections or field re-stings and lack of systemic reaction (SR) to deliberate challenge sting. METHODS: The standard 1-month interval was gradually extended to 3 months in 28 patients (mean age 26 years, range 7 to 76) allergic to bee venom (BV), yellow jacket venom, or both venoms. Nineteen patients allergic to BV were deliberately challenged by a live bee sting. In 15 patients the original SR in the field was moderate; in one patient it was mild; and in three patients it was severe. RESULTS: Mean duration receiving standard maintenance VIT before extending the 1-month interval was 17 months. No patient had an SR while receiving the 3-month VIT therapy. Two patients experienced four field re-stings while receiving the 3-month therapy with no reaction. After the live challenge, there was mild urticaria in a single patient; no SR developed in the rest of the patients. CONCLUSION: For young patients allergic to BV whose initial SR is mild to moderate and who have already received 1-month VIT for longer than 17 months, the maintenance interval may safely be extended to 3 months while preserving its protective activity against re-stings. PMID- 8006323 TI - Effects of ritanserin, a novel serotonin-S2 receptor antagonist, on the secretion of pituitary hormones in normal humans. AB - The availability of a new potent and selective serotonin-S2 antagonist, ritanserin (RIT), encouraged us to further investigate the effect of serotonin on the basal secretion of anterior pituitary hormones in normal humans. Administered in a single 30-mg dose to group 1 consisting of 10 normal women, RIT failed to affect the baseline LH, FSH, GH or TSH levels. In group 2 consisting of 20 normal subjects (ten males and ten females), the same dose of RIT decreased in parallel both ACTH and cortisol levels but only at 180 min. Group 3 consisting of 8 normal men was studied on three separate occasions seven days apart: each subject received graded doses of 10 mg, 20 mg and 30 mg RIT. The mean baseline PRL concentration at 180 min as well as the net integrated area under the hormone curve (nAUC) decreased only after the highest dose, while the baseline cortisol concentrations at 180 min as well as the corresponding nAUC values displayed a clear dose-dependent response. The findings indicated the serotonin-S2 receptors to be only partially involved in the basal secretion of ACTH in normal humans. PMID- 8006325 TI - Increased incidence of thyrotoxicosis after iodine supplementation in an iodine sufficient area. AB - The aim of this study was to determine the incidence rate of thyrotoxicosis (TT) before and during dietary-iodine supplementation in an iodine-sufficient area. POPULATION: the study was carried out in Vigo, South Galicia (northwest of Spain), from January 1977 to December 1989. The mean population throughout the study period was 267,330 inhabitants (47% males and 53% females). From January 1985, a mandatory consumption of iodinized salt on the whole population started in Galicia. This region was considered as an iodine-deficient area but Vigo is an iodine-sufficient area. MEASUREMENTS: all newly diagnosed TT cases in Vigo city within the study period were included in this study. Diagnosis of TT was based on the clinical manifestations, an elevated level of T4 and suppressed TSH values. The difference between diffuse and nodular forms of goiter was assessed by scintigraphy. The average incidence rate (AIR) was determined in two periods, before (period A, 1977-1984) and during (period B, 1985-1989) iodine supplementation. RESULTS: the AIR throughout the whole study period was 4.89 new cases per 100,000 population, 95% confidence limits 4.16 to 5.63; AIR was 1.34 for males and 8.03 for females. AIR in period B was significantly higher with respect to period A, 7.68 and 3.10 per 100,000 respectively. The confidence interval for the difference was from -20.4 to 30.1, p < 0.05. The increase of the incidence of TT was comprised of both nodular and diffuse goiters. CONCLUSIONS: dietary iodinesupplementation in iodine-sufficient areas may induce an increase of the incidence of TT.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8006324 TI - Thyroid hormone autoantibodies and their implications for free thyroid hormone measurement. AB - Thyroid hormone autoantibodies (THAA) disrupt the equilibrium between thyroid hormones and their binding proteins. This may lead to spurious estimations of free thyroxine (FT4) and triiodothyronine (FT3) by radioimmunoassay (RIA). In the present study we highlight the importance of THAA by examining the frequency of THAA in consecutive sera sent to a routine district hospital laboratory. Over a period of six months, sera were collected from 200 consecutive hypothyroid, 200 hyperthyroid and seven patients whose clinical and biochemical thyroid status were contradictory. A further 200 patients with non-thyroid autoimmune conditions, 20 patients with insulin autoantibodies and 100 healthy blood transfusion donors were studied. In all sera, both effects of antigen removal on THAA detection and where THAA were found, the effect of their removal on FT4, were examined. The frequencies of THAA amongst hypothyroid, hyperthyroid and non thyroid autoimmune conditions were 7%, 1.5% and 7.5% respectively, whilst no THAA were found in insulin autoantibody positive patients and 100 blood transfusion donors. However, THAA frequency was highest in those patients whose biochemical thyroid status was widely inappropriate to clinical state (5/7 = 64%). Sera stripped of thyroid hormones prior to THAA detection had significantly higher antibody activity than unstripped sera (p = 0.0027 and p = 0.0123 for T3 and T4 binding respectively). Free thyroxine levels measured by the Amerlex-M RIA kit after antibody removal fell in all 21 THAA positive sera tested. The correlation coefficient between antibody activity in serum with percentage fall in FT4 was 0.79 (Spearman's Rank Correlation Test).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8006326 TI - Normal plasma insulin-like growth factor I levels and impaired final stature in adult blind subjects. AB - The aim of this study was to determine if changes in IGF-1 levels and in final stature occur in blind adult subjects. Eighteen subjects (4 females and 14 males) with total blindness (Group 1) and 26 subjects (5 females and 21 males) with only light perception (Group 2), living at an Institute for blind adult subjects in Naples, Italy, were studied. Their height and weight were compared to British standards. Plasma morning IGF-1 levels, measured by IRMA method were compared to those of 18 normal controls (6 females and 12 males) matched for age and weight. A high prevalence of short stature was demonstrated especially in Group 1 (p = 0.00005 by chi-square for trend test) but was also present in Group 2 (p = 0.02). No alterations in weight distribution were observed in both groups. Basal IGF-I levels in both Group 1 and Group 2 were similar to those of controls: IGF-1 (M +/ SE), 30.9 +/- 2.9 nmol/L and 37.9 +/- 2.7 nmol/L, respectively, vs 33.3 +/- 2.9 nmol/L, NS. High prevalence of final short stature in both groups confirms a negative influence of total or partial blindness on growth. These complex mechanisms appear to involve more than alterations in GH and IGF-I secretion. PMID- 8006327 TI - Plasma glycosaminoglycans in endocrine ophthalmopathy. AB - With evidence on the important role of glycosaminoglycans (GAG) in the pathogenesis of endocrine ophthalmopathy (EO) having accumulated, the present study focused on the biochemical assessment of plasma GAG content in 37 EO patients as compared to 20 controls. Glycosaminoglycans were isolated from plasma samples by protein elimination, dialysis, and precipitation with ethanol and cetylpyridinium chloride. Patients (9.71, 5.09, 15.09 mg/100 ml; median, 25th, 75th percentile) exhibited significantly (p = 0.0021) higher plasma GAG levels than controls (4.6, 3.38, 6.8 mg/100 ml). Plasma GAG content was unrelated to age, sex, or antithyroid treatment. However, an even higher level of significance (p = 0.0001) was reached when discriminating between untreated patients with EO of recent onset (14.16, 10.35, 15.51 mg/100 ml) and controls. By contrast, steroid therapy of EO led to values (3.82, 1.85, 6.52 mg/100 ml) indistinguishable from those of the controls. Further statistical analysis of the results, based on a specificity of 95% for the control group, revealed a sensitivity of 91% for patients with untreated EO of recent onset, and a specificity of 100% for patients receiving steroid therapy. In comparison, plasma GAG content was determined in 8 untreated and in 6 treated EO patients by a second method already published. All untreated patients exhibited high GAG levels (median 2.23 mg/100 ml) whereas in treated EO patients normal plasma GAG values (0.17-0.34 mg/100 ml) were found. Follow-up determination of plasma GAG content in 7 patients undergoing steroid treatment unveiled a marked decrease of initially elevated values. These findings correlated well with clinical improvement of thyroid eye disease.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8006329 TI - Two dimensional gel electrophoresis identifies minor differences in immunologically cross-reactive 64 KDa autoantigens in the thyroid and eye muscle. AB - Among the candidate eye muscle autoantigens proposed as being relevant to the pathogenesis of thyroid-associated ophthalmopathy (TAO), a 64 kDa membrane autoantigen appears to be most closely associated with the eye disorder. We have examined the tissue localization and some of the physicochemical properties of this molecule in 3 human tissues, namely thyroid (THY), eye muscle (EM) and skeletal muscle (SKE), and in pig eye muscle (PEM), by two-dimensional (2-D) [isoelectric focusing (IEF)/sodium dodecyl polyacrylamide gel electrophoresis (SDS-PAGE)] gel electrophoresis followed by Western blotting. Antibody probes used were whole sera from patients with TAO and antibodies affinity purified from TAO sera by binding to, and elution from, a sepharose-4B column conjugated with D1, a 98 amino acid peptide fragment of a recombinant 64 kDa thyroid autoantigen. Soluble membrane proteins eluted from a slice of SDS-PAGE gel containing 60-70 kDa material was prepared from the four tissues and used as antigen for 2-D gel separation. The presence of a 64 kDa antigen in THY and EM recognized by sera from patients with TAO, but only rarely by those from normal individuals, was confirmed. Pretreatment of the eluted 60-70 kDa material with N-Glycosidase F to eliminate charge heterogeneity resulting from glycosylation differences, changed the pI and MW of molecules recognized by TAO sera, in THY and EM. This suggests that the 64 kDa molecule(s) in EM and THY targeted by sera from patients with TAO are glycoproteins and that they are different in the two tissues.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8006330 TI - Low doses of either intravenously or orally administered arginine are able to enhance growth hormone response to growth hormone releasing hormone in elderly subjects. AB - Reportedly, the responsiveness of somatotrope cells to GHRH is reduced in elderly humans but it is totally restored by arginine (ARG) which likely acts by inhibiting hypothalamic release of somatostatin. As this effect was observed after infusion of high doses of the amino acid, in this study, we compared the effect of iv administration of 30, 10 and 5 g ARG(group A, B and C, respectively) as well as oral administration of 8 g ARG(group D) on the GH response to 1 microgram/kg i.v.GHRH in 27 healthy elderly subjects (11 M and 16 F, age 70-86 yr, BMI 21-25 kg/m2). In group A (n = 7) 30 g i.v. ARG strikingly enhanced the GHRH-induced GH rise (peak, mean +/- SE: 41.5 +/- 4.4 vs 11.7 +/- 5.3 micrograms/L, p < 0.05). Similarly, in group B (n = 6) and D (n = 7) 10 g i.v. and 8 g oral ARG enhanced the GH response to GHRH (20.9 +/- 4.7 vs 8.3 +/- 2.8 micrograms/L, p < 0.03 and 31.0 +/- 5.3 vs 11.4 +/- 3.4 micrograms/L, p < 0.03, respectively). In contrast, in group C (n = 7) 5 g i.v. ARG failed to modify the GHRH-induced GH rise (6.0 +/- 1.6 vs 3.5 +/- 0.9 micrograms/L). The GH responses to GHRH alone did not significantly differ amongst groups; the GH responses to GHRH and ARG were not significantly different among groups A, B and D and were greater than the GH response in group C. These results show that the GH response to GHRH in elderly subjects is enhanced even by low iv doses of arginine and by the orally administered amino acid, the lowest effective dose being 8 g. Moreover, they imply that the combined administration of GHRH and arginine may be a useful approach to restore the impaired function of the GH-IGF axis in aging. PMID- 8006331 TI - Homology of calcitonin with the amyloid-related proteins. AB - We present evidence for a structural homology between the amino acid sequence of calcitonin (CT)--the fibrillar protein of the amyloid deposits of medullary thyroid cancer--and that of other 12 amyloid-related proteins (ARP). Seven of the 32 residues of CT are conserved in at least five ARP, and five of these seven amino acids belong to the stretch Gly2-Gln14. Gln14 is conserved in all 12 ARP and Cys7 in all eight ARP containing cysteine. The concentration of the homology in the N-terminal half of CT goes along with the knowledge that is the C-terminal region the one more important for the hormonal action of CT. Since an imbalance between synthesis and catabolism of a given ARP is believed to be the general pathogenetic mechanism of amyloidosis, the intratumoral deposition of CT in the form of amyloid fibrils would be due to the overproduction of a protein structurally similar to the ARP. PMID- 8006332 TI - The efficacy of percutaneous tetracycline instillation for sclerosis of recurrent thyroid cysts: a multivariate analysis. AB - A dichotomy exists in the literature concerning the efficacy of sclerosing agent tetracycline hydrochloride for treatment of thyroid cysts. However, the studies vary in patient selection and none employed a statistical method for simultaneous analysis of multiple factors that might affect the outcome of therapy. We, therefore, studied the efficacy of percutaneous instillation of tetracycline for eradication of recurrent thyroid cysts, using a multivariate analysis. Thirty seven patients with recurrent, cytologically benign thyroid cysts (not cured after 3 aspirations) were studied. Twenty-three patients were given tetracycline instillations [100 mg/ml, range (R): 1-4 ml]. The remainder underwent only repeated needle aspiration. They were followed for 33 +/- 12 (SD) months, R: 12 58 months. Cure was achieved in 21 out of 23 cases after tetracycline instillation within 2 +/- 1.7 months (R: 1-6 months) and in 12 out of 14 cases after aspiration alone within 9.9 +/- 11.3 months (R: 1-43 months, 4-10 aspirations). Multivariate survival analysis using the Cox proportional-hazards regression model demonstrated significantly shorter time interval before cure in the group with tetracycline instillation (p = 0.001). The volume, color or duration of cysts and levothyroxine (L-T4) treatment did not appear to influence the outcome of therapy. After initial cure by tetracycline instillation, 5 cases had relapse. Three were later cured by reinstillation of tetracycline or by repeated aspirations (R: 1-3 times). Complications of tetracycline instillation included brief episode of neck pain and development of a foreign body granuloma in a single patient. In conclusion, tetracycline instillation is a quick and effective procedure for treating recurrent thyroid cysts.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8006328 TI - Circulating growth hormone binding proteins. PMID- 8006333 TI - Isolated adrenocorticotropic hormone deficiency due to probable lymphocytic hypophysitis in a man. AB - We report a male patient who presented with severe fasting hypoglycemia in which extensive pituitary and adrenal investigations were diagnostic of isolated ACTH deficiency of pituitary origin. The finding of autoimmune subclinical primary hypothyroidism strongly suggested an autoimmune etiology of the pituitary disease. Lymphocytic hypophysitis, although very rare in male patients, has to be kept in mind when studying patients with pituitary failure of unknown origin, especially when other autoimmune endocrinopathy is present. PMID- 8006334 TI - Mycobacterium avium intracellulare suppurative thyroiditis in a patient with Hashimoto's thyroiditis. AB - A case of suppurative thyroiditis occurring in a 72-year-old woman is reported. The clinical history of this woman, treated by tianeptine for mild exogenous affective disorder and by conventional insulin therapy for long-standing insulin dependent diabetes, was remarkable for the pseudotumoral signs which led to the simultaneous diagnosis of hypothyroidism due to Hashimoto's thyroiditis and of mycobacterium avium intracellulare suppurative thyroiditis. To our knowledge, this is the second reported case of mycobacterium avium intracellulare thyroiditis. This case is also exemplary, given its occurrence in the absence of severe immunodepression, setting apart the mild impact on the immune system of affective disorder and of long duration's insulin-dependent diabetes. PMID- 8006335 TI - Long-term treatment of Nelson's syndrome by octreotide: a case report. AB - Medical management of Nelson's syndrome by drugs such as bromocriptine, sodium and magnesium valproate has provided disappointing or, at least, controversial results. We report here on the results of long-term (2 yr) treatment with the somatostatin analogue octreotide (300 micrograms daily sc) in one patient affected by Nelson's syndrome occurring after bilateral adrenalectomy for Cushing's syndrome. During treatment, skin hyperpigmentation and serum ACTH levels decreased dramatically and a slight (about 10%) reduction in tumor size, as assessed by computerized tomography, was also observed. These results suggest that octreotide may be useful for the medical management of Nelson's syndrome. PMID- 8006337 TI - The duration of prolactin secretory bursts from the pituitary is independent from both prolactin and gonadal steroid plasma levels in women and in men. AB - The intrinsic secretory characteristics of prolactin (PRL) have been investigated using newly developed algorhythms for instantaneous secretory rate (ISR) computation. PRL secretory rate, its intrinsic pulsatile characteristics and their possible dependance from gonadal steroids were investigated in five groups of subjects: a) 11 women during the follicular and luteal phase of the same menstrual cycle; b) 5 healthy postmenopausal women; c) 6 women affected by functional hyperprolactinemia; d) 5 normal men; e) 4 agonadal subjects before and during testosterone replacement therapy. All subjects underwent a 6 hours pulsatility study, from 08:00 to 14:00, sampling every 10 minutes. PRL plasma concentrations were determined using a RIA system and the presence of PRL secretory pulses was evaluated with program DETECT, both on plasma time series and after ISR computation. A distinct PRL episodic release was observed in all groups (follicular phase: 5.5 +/- 0.5, luteal phase: 6.5 +/- 0.6, postmenopause: 5 +/- 1, hyperprolactinemic women: 4.2 +/- 0.8, men: 4.8 +/- 0.4, agonadal before testosterone: 6 +/- 1, agonadal during testosterone administration: 5.3 +/- 0.3 peaks/6h), but mainly the computation of ISR allowed to demonstrate that the duration of the lactotropes secretory events was constant in all groups studied. PRL secretory bursts duration ranged between 23.1 +/- 1.8 and 25.4 +/- 2.5 minutes independently both on PRL or on sex steroid plasma levels. In conclusion, the present report shows that in different physiological conditions the intrinsic secretory bursts from lactotropes are constant in duration independently from the functional state, sex and the steroid hormone levels. PMID- 8006338 TI - Responses to gonadotropin releasing hormone agonist and antagonist administration in patients with gonadotroph cell adenomas. AB - As they are clinically silent, gonadotroph cell pituitary adenomas are usually diagnosed only when pituitary enlargement causes visual impairment or hypopituitarism. In postmenopausal women presenting with pituitary tumors it can be difficult to determine whether gonadotropin hypersecretion is due to adenomatous or normal gonadotrophs prior to surgery. The usual GnRH dependency of gonadotropin secretion may be of diagnostic and therapeutic value. We therefore evaluated responses to the GnRH antagonist Nal-Glu-GnRH and to the long-acting GnRH agonist D-Trp6 (3.75 mg IM) in 9 and 4 patients with FSH- and/or alpha subunit-secreting adenomas, respectively. Six of the 7 patients with FSH secreting adenomas and one of the 2 patients with pure alpha subunit-secreting adenomas were studied postoperatively. In these patients postoperative FSH and/or alpha-subunit levels remained elevated and pituitary imaging by CT-scan and/or MRI disclosed tumoral residues. In the 2 remaining patients testing was performed preoperatively. A single administration of 5 mg Nal-Glu to the 7 patients with FSH-secreting adenomas produced a slight but significant fall in above-normal FSH levels from 24.4 +/- 15.4 IU/l to a nadir of 20.3 +/- 11.9 IU/l (-17%, p < 0.05) 20 h following the injection. LH levels fell markedly in the 6 patients with normal basal serum LH concentrations to those observed in hypophysectomized patients, while mean alpha-subunit levels were not modified. Alpha-subunit levels were not modified by Nal-Glu administration in the 2 patients with alpha-subunit secreting adenomas.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8006340 TI - Research considerations: guardianship and the vulnerable elderly. AB - 1. The use of legal guardianship for the elderly is increasing due to the increase in numbers of vulnerable elders and the subsequent dynamic effect on their families and communities. 2. Although the guardianship system provides a necessary service, the effects on "wards of the court" can lead to further physical and psychological deterioration due to their loss of all major decision making powers. 3. There is an assumption that the closest living relative would be the best guardian. There also is an assumption that elders who are confused or disoriented in dealing with money or business affairs require full guardianship. The validity of these assumptions, without assessment and intervention of geriatric specialists, is questionable. PMID- 8006336 TI - Cytokines as mediators in the regulation of the hypothalamic-pituitary adrenocortical function. PMID- 8006341 TI - Policy implications for life care environments. AB - 1. Life care or continuing care retirement communities (CCRCs) offer numerous services and financial options from which to choose. 2. Advantages of CCRCs include continuity of living, quality of life factors, close proximity of social and health care services, and formal and informal support systems. 3. Problems of CCRCs include lack of uniform standards, fiscal lack of accountability, and fragmentation. 4. Nurses must be knowledgeable about CCRCs, both from the stand point of counseling older persons on the benefits and pitfalls of residing in a CCRC and to influence health care policy regarding these communities. PMID- 8006339 TI - Usefulness of thyrotropin-releasing hormone test, SMS 201-995, and bromocriptine in the diagnosis and treatment of gonadotropin-secreting pituitary adenomas. AB - Five patients with gonadotropin-secreting pituitary adenomas were studied. The utility of gonadotropin response to TRH stimulation in the diagnosis and follow up of these tumors was evaluated, as well as the effects of somatostatin analogue SMS 201-995 and bromocriptine on gonadotropin release. Three patients had FSH and LH secreting adenomas while the other two tumors secreted FSH and alpha-subunit. Transsphenoidal resection of the pituitary adenomas were performed in all patients. Following preoperative TRH administration (400 micrograms i.v.), marked increases were observed in FSH levels in two cases, in LH levels in three and in alpha-subunit in one. The FSH and LH responses to t.his stimulus persisted in the same patients after surgery. Following acute bromocriptine administration (5 mg orally), FSH was reduced in all cases by 19% to 46%, LH in three cases by 50-67% and alpha-subunit in one by 33%. In patient no. 5, with persistent high FSH levels in the immediate postoperative period, long-term bromocriptine treatment was administered (15 mg/d orally), resulting in normalization of FSH levels 6 months later, although the size of the tumor was not reduced. After acute SMS 201 995 administration (100 micrograms sc) FSH decreased in two cases by 38% and 76%, LH in three by 30-56% and alpha-subunit in one by 20%. We conclude that gonadotropin response to TRH stimulation is useful in the diagnosis and follow-up of patients with gonadotroph adenoma. Bromocriptine and SMS 201-995 may be effective as coadjuvant treatment following surgery and radiotherapy in these patients, although long-term studies will be necessary to confirm these proposals. PMID- 8006342 TI - Effectiveness of pelvic muscle exercises in reducing urge incontinence among community residing elders. AB - 1. Urinary incontinence is a costly and prevalent problem, affecting 15% to 39% of all community residing elders. 2. Some elders suffering from urge incontinence prefer pelvic muscle exercises to bladder training as the behavioral intervention of choice. 3. Although pelvic muscle exercises are frequently associated as an intervention for stress incontinence, they have been found to be effective in significantly reducing urge incontinence. 4. Nurses are in a key position to identify and treat urinary incontinence among the elderly, and should incorporate continence restoration interventions into their practice. PMID- 8006344 TI - Nursing home patients: liaison nurse visits influence recidivism. AB - 1. Nursing home residents who were visited at least once every 60 days by VA nurses (who were master's prepared and had experience in gerontological nursing) had fewer emergency room visits and hospital readmissions than those who were not visited. 2. The establishment of a good rapport between the liaison nurses and the nursing home staff was essential in initiating nursing interventions. 3. The recommendations most often made by the liaison nurses to the nursing home staff were for collaborative actions with other disciplines. PMID- 8006343 TI - Professional support: an essential component in a cardiovascular risk reduction program. AB - 1. A comprehensive cardiovascular risk reduction program includes cardiovascular risk reduction factors combined with professional support and the importance of health as an attainment of life goals. 2. This study revealed significant reduction in weight, serum glucose, and diastolic blood pressure levels following participation in the program. 3. Professional support, or continuing interaction with health professionals, assisted consumers to continue motivation and reinforce health promoting activities. PMID- 8006345 TI - Gerontological nursing: overcoming barriers to preparation and practice. AB - 1. The care available to the increasing number of elders requiring nursing home care is becoming more restrictive and expensive, and of poorer quality. 2. Educators and administrators must collaborate to develop strategies that will attract and retain prepared nurses to long-term care. 3. Studies have shown that nursing home employment of well-prepared nurses is cost-effective and increases the quality of patient care. PMID- 8006346 TI - Elder abuse, neglect, and mistreatment. PMID- 8006347 TI - Behavioral slowing: how nurses can help patients to adapt. PMID- 8006348 TI - Acute care gerontological nursing: its time has come. PMID- 8006349 TI - Research concerns. Aging as perceived by Saudi elders. AB - 1. Theories of aging popularly taught to nurses are based on Western culture, which may not be appropriate for other cultures. 2. The continuity theory of aging was not supported with Saudi patients in a test of hypotheses derived from the theory. 3. Nurses must be aware that Western theories may not be valid in other cultures. Nurses, therefore, must be cautious regarding generalizations concerning aging--individuals, regardless of age, must be treated as unique. PMID- 8006350 TI - Physical restraints: has OBRA made a difference? AB - 1. A component of the Omnibus Budget Reconciliation Act of 1987 declared that nursing home residents have the right to be free from physical or chemical restraints that are not required to treat specific "medical symptoms." 2. The literature suggests that the use of restraints has a negative influence on the caregiving process by restricting creativity and individual treatment. 3. Decreased reliance on restraints can be accomplished in nursing homes without an increase in staffing. 4. Transition to limited restraint use requires an organized, planned effort to change attitudes, beliefs, practices, and policies of a facility. PMID- 8006351 TI - Hearing in the elderly. Relation of hearing loss, loneliness, and self-esteem. AB - 1. The prevalence of hearing impairment increases with age. Hearing handicap resulting from hearing loss may lead to psychosocial problems in elders. 2. Previous studies have shown relations among hearing handicap, loneliness and low self-esteem, but those studies focused on populations other than elders. 3. Early detection of hearing handicap and appropriate interventions promote increased independence and preserve the ability of elders to interact with their environment. PMID- 8006352 TI - Mental status guide: FROMAJE for use with frail elders. AB - 1. There is no single pathognomonic sign, symptom, or clinical or laboratory test for making the diagnosis of dementia. A key element of the examination must be the inclusion of a mental status evaluation. 2. The FROMAJE--an acronym for Function, Reasoning, Orientation, Memory, Arithmetic, Judgment, and Emotion- Mental Status Guide (FMSG) has the advantage of a clear relationship between the acronym and the characteristics being measured. 3. The FMSG is meant to serve as a guide for the primary care clinician, who may have little experience in formal mental status testing. It is a convenient cognitive screening instrument to detect dementia in the elderly. PMID- 8006354 TI - Reflections on the evolution of care in nursing homes. PMID- 8006353 TI - Development of the refined ADL Assessment Scale for patients with Alzheimer's and related disorders. AB - 1. Most activities of daily living (ADL) scales currently available for assessment of the older person's functional level were developed for the physically (not cognitively) impaired individual. 2. The Refined ADL Assessment Scale (RADL) measures three dimensions of functional ability: the components of a given task in sequential order, degree of assistance needed to carry out the task, and the amount of time needed to complete the task. 3. Each of the 14 tasks on the RADL is broken down into its simpler component parts, a process called task analysis. 4. The RADL may be used as a guide to providing assistance with the basic ADLs and to evaluate an individual's improvement with treatment. PMID- 8006355 TI - Survey results: academic courses of women's health across the lifespan. AB - 1. Today's college women are older than college women of 10 or 20 years ago; women's health courses must reflect this demographic change. 2. An awareness of older women's health concerns must be an essential component of any women's health course. 3. Nurses' preparation and traditional advocacy roles make them ideal to teach women's health courses. PMID- 8006356 TI - Hope: an essential human need in the elderly. AB - 1. Hope is essential for the adaptation to illness and to transcend the limitations of aging. 2. Hope generates energy that enables individuals to cope with numerous problems and losses, overcome obstacles in life, and continue functioning during chronic illness. 3. Hope thrives in the context of a caring relationship. PMID- 8006357 TI - Complementarity between advanced practice in psychiatric and gerontological nursing. PMID- 8006358 TI - Foreshadow. PMID- 8006359 TI - Early infantile surgery for birth-related brachial plexus injuries: justification requires a prospective controlled study. PMID- 8006360 TI - Birth-related upper brachial plexus injuries in infants: operative and nonoperative approaches. AB - Advances in intraoperative neuroelectrodiagnostic testing and microneurosurgical techniques have made it possible to accurately explore the brachial plexus of neonates. Since 1987, we have followed 250 infants with birth-related brachial plexus injuries, and successful operations have been completed on more than 70 infants. Fifty infants who underwent surgery have been followed for more than 18 months. Based on these accumulated data and historical data, this review describes both nonoperative and operative approaches to the treatment of birth related brachial plexus injuries. PMID- 8006361 TI - Childhood pseudotumor cerebri: clinical and intracranial pressure response to acetazolamide and furosemide treatment in a case series. AB - The purpose of this study was to investigate the efficacy of combined therapy with acetazolamide and furosemide in normalizing intracranial pressure in children with pseudotumor cerebri. The role of repeated lumbar cerebrospinal fluid pressure monitoring in evaluating the response to therapy is also demonstrated. Continuous 1-hour lumbar cerebrospinal fluid pressure monitoring was done in eight children with pseudotumor cerebri on admission and at weekly intervals until the baseline pressure had normalized. (One child had two episodes of pseudotumor cerebri). All patients were treated with oral acetazolamide and furosemide until papilledema had cleared. Raised intracranial pressure was present on admission in all nine episodes of pseudotumor cerebri. Six children had an increased baseline cerebrospinal fluid pressure, whereas raised intracranial pressure was diagnosed in three children on account of an abnormal pulse wave and/or pressure waves. The mean baseline pressure was significantly lower after the 1st week of treatment than on admission (P = .007) and normalized in all patients within 6 weeks of start of therapy. All children had a rapid clinical response. Combined therapy with acetazolamide and furosemide is an effective first-line method of treating raised intracranial pressure in children with pseudotumor cerebri. The good correlation found between the clinical response and normalization of baseline cerebrospinal fluid pressure suggests that clinical monitoring of treatment is adequate in most children with this condition. PMID- 8006363 TI - Focal cerebral metabolic abnormality in a patient with continuous spike waves during slow-wave sleep. AB - We report an 11-year-old boy with continuous spike-wave discharges during sleep accompanied by partial motor and atypical absence seizures, psychomotor regression, and severe behavior problems. During wakefulness, epileptiform discharges occurred over the right parietal region, suggesting that the continuous spike-wave discharges during sleep were a manifestation of secondary bilateral synchrony. Bilateral suppression of the spike-and-wave activity was observed after right-sided intracarotid amobarbital injection, further supporting the impression of secondary bilateral synchrony. The right superior temporoparietal increase in metabolic activity during continuous spike-wave discharges and noncontinuous spike-wave discharges was seen on [18F]fluorodeoxyglucose positron emission tomography and supports a right temporoparietal focus in our case. The presence of a focal abnormality suggests that surgical therapy may be effective. PMID- 8006362 TI - Familial adrenal insufficiency, achalasia, alacrima, peripheral neuropathy, microcephaly, normal plasma very long chain fatty acids, and normal muscle mitochondrial respiratory chain enzymes. AB - Adrenal insufficiency has been associated with adrenoleukodystrophy and adrenomyeloneuropathy. In these diseases, plasma very long chain fatty acids are elevated. Peripheral neuropathy is frequently seen in adults with adrenomyeloneuropathy. We encountered two first cousins with adrenal insufficiency, who also developed peripheral neuropathy, achalasia, alacrima, and microcephaly. However, plasma very long chain fatty acids, pipecolic acid, phytanic acid, and cranial computed tomographic scan were normal. Muscle mitochondrial respiratory chain enzymes were also normal. This syndrome of adrenal insufficiency, achalasia, alacrima, microcephaly, and peripheral neuropathy is different from either adrenomyeloneuropathy or adrenoleukodystrophy. PMID- 8006364 TI - Idiopathic intracranial hypertension in children: the Iowa experience. AB - Idiopathic intracranial hypertension is an uncommon condition in children and is seen only about once a year in a large referral hospital. Sex incidence is equal, and obesity is a feature in about one third of patients. This article reviews the 30-year experience in an institution where idiopathic intracranial hypertension in adults has been extensively studied. Symptomatic causes of intracranial hypertension and both medical and surgical therapeutic options are reviewed. PMID- 8006365 TI - Pediatric leptomeningeal metastasis: 111In-DTPA cerebrospinal fluid flow studies. AB - Nine children (five girls and four boys) ranging in age from 1 to 18 years (median age, 12 years) with leptomeningeal metastasis were evaluated for cerebrospinal fluid compartmentalization with cerebrospinal fluid flow studies using ventricular diethylenetriaminepentaacetic acid labeled with indium 111 (111In-DTPA). Histologic diagnosis included medulloblastoma (two), primitive neuroectodermal tumor (two), acute lymphoblastic leukemia (two), pineoblastoma (one), ependymoma (one), and anaplastic astrocytoma (one). Sixteen 111In-DTPA cerebrospinal fluid flow studies were performed, of which nine demonstrated normal anterograde cerebrospinal fluid flow of radionuclide, with the following cerebrospinal fluid compartment median times to appearance, with ranges in parentheses: ventricles, 1 minute (0 to 3 minutes); cisterna magna/basal cisterns, 5 minutes (3 to 5 minutes); cervical subarachnoid space, 8 minutes (5 to 10 minutes); thoracic subarachnoid space, 15 minutes (10 to 30 minutes); lumbar subarachnoid space, 35 minutes (20 to 45 minutes); and sylvian cistern, 80 minutes (60 to 90 minutes). Blockage of normal anterograde cerebrospinal fluid flow was seen in seven 111In-DTPA cerebrospinal fluid flow studies in the following cerebrospinal fluid compartments: cervical subarachnoid space (four), lumbar subarachnoid space (two), and cisterna magna/basal cisterns (one). Five 111In-DTPA cerebrospinal fluid flow studies were performed after demonstration of cerebrospinal fluid compartmentalization and treatment with limited-field radiation therapy to involved regions; cerebrospinal fluid flow blocks resolved in three. In conclusion, cerebrospinal fluid compartmentalization, as shown by radionuclide ventriculography, is a common occurrence in pediatric leptomeningeal metastasis (four of nine patients, or 44%) and may be palliated by involved-field radiotherapy. PMID- 8006367 TI - Dystrophin and DNA diagnosis in a large pediatric muscle clinic. AB - Eighty-seven unrelated patients from a large muscle clinic setting were analyzed by DNA for deletions in the dystrophin gene for diagnosis of Duchenne/Becker muscular dystrophy. The clinical phenotype of the patient population included 72% Duchenne, 13% Becker, and 15% outlier patients. Dystrophin gene deletions were detected in 61% of these patients, and disease phenotype was predicted by DNA with an accuracy of 95%. While DNA did not confirm diagnosis in all patients, dystrophin analysis of muscle biopsies, when available, predicted a disease phenotype. In the 66 patients in which muscle biopsies were available for analysis, the results of the dystrophin analysis agreed with actual clinical phenotype with 86% accuracy. Less agreement between dystrophin and clinical phenotype predictions were found in the Becker patient population. We suggest that, in at least 61% of Duchenne/Becker patients, DNA analysis provides a rapid and accurate diagnosis. DNA is less invasive and less expensive than biopsy and may allow family risk assessment. Therefore, DNA analysis may become the first recommended laboratory procedure for Duchenne/Becker diagnosis, and muscle biopsy with dystrophin analysis may become necessary only for those patients with undetectable gene mutations. PMID- 8006366 TI - Neuroimaging in infantile autism. AB - Metabolic findings using [18F]fluorodeoxyglucose (FDG) with positron emission tomography (PET) and correlative anatomic findings with computed tomography (CT) or magnetic resonance imaging (MRI) were characterized in 13 children with infantile autism. Four of 13 patients had both an abnormal FDG-PET and an abnormal MRI, whereas seven of 13 patients had both a normal FDG-PET and a normal CT or MRI. Sixteen of a total of 195 brain areas qualitatively examined with FDG PET had a hypometabolic abnormality on PET. Three of the five abnormal structural imaging studies revealed neuronal migrational anomalies (focal pachygyria). In two of the five patients with anatomic abnormalities, these were noted only after knowledge of the FDG-PET findings. Our experience reveals that anatomic and metabolic abnormalities can be found in children who exhibit autistic behavior. An FDG-PET study may provide evidence of metabolic dysfunction after an initially unremarkable MRI scan because subtle anatomic abnormalities (as those seen with neuronal migrational anomalies) may be found only after knowledge of a regional metabolic abnormality. PMID- 8006369 TI - Holocarboxylase synthetase deficiency: a treatable metabolic disorder masquerading as cerebral palsy. AB - A 20-month-old boy of Jewish-Turkish origin presented with severe metabolic acidosis. He was born prematurely and had bacteremia during the neonatal period. Scaly skin eruption, developmental delay, generalized muscular hypertonia, and mild ventriculomegaly were noted during the 1st year. Holocarboxylase synthetase deficiency was diagnosed, and biotin and carnitine were administered. The skin rash and the organic aciduria resolved within several days, and at 30 months, his psychomotor development was appropriate for age. Metabolic evaluation should be performed in patients with combined neurologic and dermatologic symptoms even when medical history suggests a nonmetabolic etiology. PMID- 8006368 TI - Episodic brainstem compression masquerading as electrodecremental seizures. AB - An 8-year-old boy developed generalized tonic spasms lasting minutes accompanied by an electrodecremental event on electroencephalogram in association with increased intracranial pressure caused by shunt malfunction. The electroencephalographic abnormalities and clinical attacks occurred despite an otherwise normal neurologic examination, normal initial opening pressure on lumbar puncture and shunt tap, and only mild ventricular dilation revealed by brain imaging. There was no improvement with antiepileptic drugs. Further signs of uncal herniation led to repeat tap of the shunt, revealing a pressure of 800 mm of water. After revision of the shunt "seizures" stopped and the electroencephalogram returned to normal. Antiepileptic drugs were discontinued, with no recurrence of events. PMID- 8006370 TI - Maternal-fetal HLA sharing and risk of newborn encephalopathy and seizures: a pilot study. AB - A pilot case-control study was done to collect data on whether susceptibility to newborn encephalopathy and neonatal seizures is influenced by the degree of maternal-fetal sharing of HLA antigens. Cases included 13 infants with moderate or severe newborn encephalopathy and seven infants with neonatal seizures but no other signs of encephalopathy. Controls were neurologically normal infants matched to cases by date of birth, sex, race, and payment status. Infants and their mothers were typed for HLA-A, -B, -DR, and -DQ antigens. The observed frequency of sharing of maternal antigens was greater than expected (ie, 0.5) for cases compared to controls at the HLA-B, -DR, and -DQ loci but not for HLA-A. The risk of neurologic problems in the neonatal period was increased 6.3 times when there was more than one match at the HLA-DR or -DQ locus. Placental abnormalities were noted at delivery only among cases, and the mean placental weight in cases was 598 g versus 695 g in controls. Further studies with sample sizes sufficiently large to statistically test this hypothesis are needed. PMID- 8006371 TI - Immunoglobulins in the treatment of Guillain-Barre syndrome in early childhood. AB - This is a prospective study on the use of immunoglobulins in the treatment of Guillain-Barre syndrome in four children, three of whom were younger than 3 years of age. All of them were unable to walk and were still deteriorating when the treatment was started. Three patients started recovering within 24 hours, and all the patients were fully mobile within 6 weeks after receiving first dose of immunoglobulins. This report shows the efficacy of intravenous immunoglobulins in the treatment of young children presenting with acute Guillain-Barre syndrome. PMID- 8006373 TI - Sturge-Weber syndrome: recommendations for surgery. PMID- 8006372 TI - Hemispheric processing and methylphenidate effects in attention-deficit hyperactivity disorder. AB - To advance our understanding of attention-deficit hyperactivity disorder and medication effects we draw upon the evidence for (1) a neurotransmitter imbalance between norepinephrine and dopamine in attention-deficit hyperactivity disorder and (2) an asymmetric neural control system that links the dopaminergic pathways to left hemispheric processing and links the noradrenergic pathways to right hemispheric processing. It appears that attention-deficit hyperactivity disorder may involve a bihemispheric dysfunction characterized by reduced dopaminergic and excessive noradrenergic functioning. In turn, favorable medication effects may be mediated by a restoration in neurotransmitter balance and by increased control over the allocation of attentional resources between hemispheres. PMID- 8006374 TI - New insights into the pathogenesis of congenital myopathies. AB - Congenital myopathies are developmental disorders of muscle that are best understood in the context of ontogenesis. Segmental amyoplasia results from a defective somite, usually because of lack of induction by the notochord and neural tube; the connective tissue matrix of the muscle is derived from lateral mesoderm and is present, but the myocytes are derived from somitic mesoderm and are replaced by adipose cells. Generalized amyoplasia is due to defective myogenic regulatory genes. X-linked recessive myotubular myopathy is associated with overexpression of vimentin and desmin, fetal intermediate filaments that attach to nuclear, mitochondrial, and inner sarcolemmal membranes and Z-bands of sarcomeres to preserve the morphologic organization of the myotube. Neonatal myotonic dystrophy is a true maturational delay in muscle development. Congenital muscle fiber-type disproportion is a syndrome of multiple etiologies but in some cases is associated with cerebellar hypoplasia and may be the result of abnormal suprasegmental stimulation of the developing motor unit at 20 to 28 weeks' gestation, mediated through bulbospinal pathways but not the corticospinal tract. Maturational delay of muscle in late developmental stages is less specific than in stages before midgestation. The Proteus syndrome is a muscular dysgenesis; abnormal paracrine growth factors and perhaps altered genes that regulate muscle differentiation and growth, such as myoD and myogenin, are the suspected cause. Focal proliferative myositis may be another example of a "paracrine myopathy." PMID- 8006375 TI - Elbow flexion contracture in Erb's palsy. PMID- 8006377 TI - The Paladin problem. PMID- 8006376 TI - Case report of homocystinuria: clinical, electroencephalographic, and magnetic resonance imaging findings. PMID- 8006378 TI - Peer review of medical expert witnesses. PMID- 8006379 TI - Migration and development of the larvae of Gnathostoma nipponicum in the rat, second intermediate or paratenic host, and the weasel, definitive host. AB - Migration and development of the larvae of Gnathostoma nipponicum in the rat as second intermediate or paratenic host and the weasel as definitive host were examined to clarify the pathogenesis in each animal. The advanced third-stage larvae (AdL3) given orally to rats remained in the stomach for 12 h post infection (PI). After that, larvae transiently invaded various organs and finally moved into the muscle within 48 h. The percentage of eosinophils in the blood taken from the jugular vein of rats infected with AdL3 reached a maximum (about 6%) on day 20 PI and then decreased. IgG antibody titre for G. nipponicum measured by ELISA began to increase on day 5 PI and reached a plateau on day 20 PI. The AdL3 given orally to weasels moved from the stomach into the muscle and then increased in size. Half of them invaded the muscle within 5 days, whereas the majority of them invaded the muscles within 20 days PI. Morphology of worms which invaded the muscles indicated that they were still the larval form with three rows of hooklets on the head bulb. The larvae in the muscles developed to young adult worms with seven rows of hooklets on the head bulb within 40 days PI. These young adult worms invaded the oesophageal wall and formed a tumour within 60 days PI. It was presumed that worms invaded the oesophageal wall through the adventitia. Ferret and mink were shown to be potential final hosts of G. nipponicum. PMID- 8006380 TI - The infection characteristics of the antelope schistosomes, Schistosoma margrebowiei and S. leiperi, in inbred BALB/c mice and in Mastomys coucha. AB - Detailed studies were carried out to assess the infection characteristics of the antelope schistosomes in BALB/c mice and Mastomys coucha. Both schistosome species reached sexual maturity in these hosts. However, they differed markedly in terms of egg production rates and preferred sites of tissue egg deposition. Tissue egg deposition commenced between 4 and 5 weeks in the case of Schistosoma margrebowiei and between 6 and 7 weeks in the case of S. leiperi. Tissue egg accumulation rates of S. leiperi were calculated to be 334 and 311 eggs/gravid worm pair/day in mice and M. coucha, respectively. The fecundity of S. margrebowiei was found to be substantially greater (approximately 5 times; daily output ranging from 1600-1900 eggs/gravid worm pair). While S. leiperi infections remained relatively stable in both hosts during the study period (i.e. up to 15 weeks after onset of egg laying), S. margrebowiei infections were observed to deteriorate rapidly in M. coucha. PMID- 8006381 TI - Onchocerca volvulus infections in chimpanzees: an assessment of the requirements for vaccination trials. PMID- 8006382 TI - Population dynamics of the metacercarial stage of the bucephalid trematode, Labratrema minimus (Stossich, 1887) from Salses-Leucate lagoon (France) during the cercarial shedding period. AB - The population dynamics of Labratrema minimus (Stossich, 1887) metacercariae (Trematoda, Bucephalidae) were studied in its second intermediate fish host Atherina boyeri from Salses-Leucate lagoon (Northwest Mediterranean Sea, South of France), during the cercarial shedding period. The infection parameters (prevalence and mean abundance of infection) showed the high susceptibility of silversides (juveniles and adults) to infection. The observed variation in the mean abundance of infection with respect to time and host size was explained by (i) the susceptibility of A. boyeri to multiple successive infections (increase in abundance of infection with host length and raising of parasite burden until August) and (ii) the loss, probably by more rapid death, of heavily infected silversides from each host size group (decrease in abundance of infection in September within each host size group, stability of the parasite burden within the older class of hosts over the whole period, premature decrease in the condition factor in August). Finally, it was deduced that the infection pattern observed over the May-September period was a dynamic process controlled by: availability of infective cercariae, influx of newborn silversides free of metacercariae until September, high susceptibility of juvenile and adult A. boyeri to infection, metacercarial loss and probably by parasite-induced host mortality. PMID- 8006383 TI - Experimental transfer of Paragonimus westermani from rodents to rodents following subcutaneous and intraperitoneal routes. AB - In order to investigate the experimental transfer of Paragonimus westermani from rodents to rodents following subcutaneous and intraperitoneal routes, 13 rats and 23 mice were inoculated with a total of 115 (1 mature and 114 immature) worms of P. westermani subcutaneously and intraperitoneally. The age of worms before transfer was 25-193 days. The transfer was performed immediately after worm collection from rodents which were killed at various intervals from 4 to 144 days after infection. The location, development and size of worms were recorded. An infection rate of 58% (or 21/36) was demonstrated in rodents after experimental transfer of P. westermani by intraperitoneal and subcutaneous routes. Twenty seven worms were recovered, giving a worm recovery rate of 23.5%. The rate was significantly higher by the subcutaneous route (34.8%) than by the intraperitoneal route (20.7%) but no difference was found between mice (23.9%) and rats (23.0%). The sizes of worms in the abdominal cavity, pleural cavity and thoracic muscles of mice, and in the leg muscles of rats were much less than in the pleural cavity and lung cysts of rats. A mature worm (7 x 5 mm) and numerous eggs were found in the uterus and pleural cavity of one rat. It is evidence that these rodents are unfavourable definitive hosts of P. westermani, because the worm size, infectivity, maturation and egg production are usually very low. However, the worms are usually widely distributed in their rodent hosts and remain small in size for a long period. Therefore, these rodents are good paratenic hosts for P. westermani and can play an important role in infecting cats and dogs with P. westermani in the laboratory. PMID- 8006384 TI - The development of new foci of echinococcosis in northern Israel: prevalence in domestic animals. AB - In a survey carried out in 1991-1992 in the town of Yirka in Northern Israel, 49 dogs were examined for Echinococcus granulosus infection and abattoir data, based on organs condemned for the presence of parasites, was collected. The presence of E. granulosus by arecoline test was demonstrated in 7 (14.2%) of the dogs examined, but not parasites were found in the intestines of five stray dogs shot in the area. A survey of sheep slaughtered in the local abattoir during a one month period revealed Echinococcus cysts in 10% of the 255 animals examined. No Echinococcus parasites were detected in 21 dogs examined 3 months after the initiation of praziquantel treatment. Echinococcosis seems to be a very serious public health problem in Israel and a control programme needs to be given a high priority. PMID- 8006385 TI - The miracidium of Transversotrema patialense (Soparkar, 1924). AB - The miracidium of Transversotrema patialense (Digenea: Transversotrematidae) has 21 epidermal cells arranged in four tiers with an epidermal formula of 6, 9, 4, 2. The penetration gland is large, conspicuous, contains a posterior globular part with 6 prominent nuclei and opens out through 6 pores arranged in two lateral groups at the tip of the apical papilla. The miracidium lacks lateral papillae, possesses a well developed subepithelium, a pair of flame cells and a germ ball. PMID- 8006386 TI - Karyometrical analysis of Microsomacanthus spasskii and M. spiralibursata. AB - Analysis of Giemsa-stained mitotic metaphase plates of Microsomacanthus spasskii and M. spiralibursata (Cestoda:Hymenolepididae) revealed the diploid chromosome numbers for both species to be 2n = 6. The karyotypes are remarkably similar in general morphology; they both consist of three pairs of metacentric or meta submetacentric chromosomes graded in size from 4.3 to 7.0 microns. Slight interspecific differences exist in the position of the centromere of chromosomes of the pair 3. Based on existing chromosome data the possible pathways of the karyotypic evolution within the family Hymenolepididae are discussed. PMID- 8006388 TI - Fasciola hepatica: the infection rate and the development of redial generations in Lymnaea truncatula exposed to miracidia after experimental desiccation and activation in water. AB - Adult Lymnaea truncatula were subjected to 10 days of experimental desiccation and then remained in water for 1 or 8 days before each was exposed to a single miracidium. The infection rate was lower in these snails than in infected controls that were not exposed to stress (52-54% vs 73%). The redial burden clearly decreased in stressed snails (18-25 rediae per snail) than in controls (43 rediae). This numerical decrease concerned essentially: i) live independent rediae of the first generation and the first cohort of the second generation, and ii) dependent rediae of subsequent generations. Mature rediae were more numerous in the first cohort of the second generation than in the other generations. Desiccation before exposure limited the size of the redial burden but placement in water for 8 days just after the stress attenuated the effects of this factor. PMID- 8006387 TI - Characterization of the surface polypeptides of Strongyloides ratti: a comparison of homogonic and heterogonic strains. AB - Surface iodination, extraction and SDS-PAGE analysis techniques were employed to characterize and compare the surface polypeptides of two strains of Strongyloides ratti. Third stage infective larvae and parasitic adults of homogonic and heterogonic strains were studied using a variety of surface labelling procedures and detergents for the extraction of labelled molecules. Profiles obtained from SDS-PAGE analysis demonstrated that homogonic and heterogonic strains of S. ratti have identical surface antigens. PMID- 8006389 TI - Studies on the karyotype and gametogenesis in Trichuris muris. AB - The cytological study of males and females of Trichuris muris (Schrank, 1788) revealed the diploid number of chromosomes to be 2n = 6. The sex determining mechanism was XX female/XY male. All the chromosomes were subtelocentric. Sex chromosomes formed the smallest pair, but X and Y were difficult to distinguish morphologically. Chromosome changes during gametogenesis in both sexes followed a classical pattern except in the male prophase and metaphase I. Four male autosomes formed two bivalents, each with one proximal chiasma with strict localization, while sex chromosomes X and Y formed two univalents. Female chromosomes formed three rod bivalents of normal type, which possessed three, two and two chiasmata. PMID- 8006390 TI - Further evaluation of a perfusion technique for the recovery of Dictyocaulus viviparus from bovine lungs. AB - A further modification of a lung perfusion technique was evaluated by examining the recovery rate of 14-day-old Dictyocaulus viviparus worms from the excised lungs of 15 dead bovine calves. Up to 89% of the total number of worms found in 12 l of perfused fluid was recovered in the first 4 l collected. The application of this observation will increase the efficiency of the routine laboratory diagnosis of D. viviparus infection. PMID- 8006391 TI - Cross protection against Taenia taeniaeformis in rats vaccinated with non-viable oncospheres of Asian Taenia or T. saginata. AB - It was determined to examine whether rats injected with non-viable oncospheres of Asian Taenia or Taenia saginata became resistant to challenge infection with eggs of Taenia taeniaeformis, since (a) metacestodes of Asian Taenia and T. taeniaeformis develop in the liver of pigs and rats, respectively, and (b) Asian Taenia and T. saginata have human origins. Rats injected intravenously or subcutaneously with complete Freund's adjuvant with non-viable oncospheres of Asian Taenia showed statistically significant resistance to challenge infection with eggs of T. taeniaeformis, whereas those injected with non-viable oncospheres of T. saginata did not show any resistance. PMID- 8006392 TI - Occurrence of Angiostrongylus vasorum in the lungs of the Brazilian fox Dusicyon vetulus. AB - Angiostrongylus vasorum infection was detected for the first time in eight foxes (Dusicyon vetulus) captured in the south of the State of Minas Gerais, Brazil. Two crossbred dogs were successfully infected orally with larvae from the foxes' faeces. PMID- 8006393 TI - An antigenic recombinant fusion protein from Trichinella spiralis induces a protective response in BALB/c mice. AB - A previously reported recombinant lambda Ts39 fusion protein (FP) derived from Trichinella spiralis larvae was purified by affinity chromatography using an anti beta-galactosidase antibody conjugated column and the effect of FP on induction of a protective response in mice was studied. BALB/c mice were injected three times at weekly intervals with FP emulsified in an equal volume of Freund's complete adjuvant and one week after the last injection mice were each challenged with a lethal dose of 1200 L1 larvae of Trichinella spiralis. As a result, the FP induced significant protection. Mice were also infected orally with 250 L1 larvae each after injection of the FP. On the 35th day of infection, immunized mice with the FP harboured 78% fewer muscle larvae than saline controls. Also, the numbers of adult worms in the small intestine were smaller in FP injected mice than saline controls on day 6 and 9 of the infection. These results suggest that the recombinant lambda Ts39 FP is a potentially valuable antigen for vaccine development. PMID- 8006394 TI - Does corticosteroid pretreatment enhance the effect of alfa interferon treatment in chronic hepatitis B? PMID- 8006395 TI - Treatment of chronic hepatitis B in children with prednisone followed by alfa interferon: a controlled randomized study. AB - The efficacy and safety of sequential treatment with prednisone and interferon was evaluated in a randomized, controlled study on 43 children with biopsy proven HBsAg/HBeAg/hepatitis B virus-DNA positive, anti-delta negative, chronic hepatitis (34 chronic persistent hepatitis, 9 chronic active hepatitis). Patients received either a 1-month course of prednisone (0.6 to 0.3 mg/kg per day) followed by interferon alfa-2a (3 MU/m2, thrice weekly, for 12 months; 22 patients) or no treatment (21 patients). At the end of the study (20 months), clearance of hepatitis B virus-DNA and HBeAg seroconversion were observed in nine (41%) of the patients treated with prednisone and interferon and in two (9.5%) of the untreated controls (p = 0.020). Two of the treated patients who lost HBeAg, also cleared HBsAg. In the treated group, 13 (59%) patients had stable normal levels of alanine aminotransferase on their last examination. The baseline serum level of hepatitis B virus-DNA was an important predictor of response. In fact, HBeAg clearance was observed in 75% of patients with a baseline hepatitis B virus DNA level lower than 100 pg/ml and in none with a level above 100 pg/ml. We suggest that combined treatment with prednisone followed by alfa-interferon may be safe and effective in inducing a stable clearance of HBeAg and, in some cases, of HBsAg in children with chronic hepatitis B and with a low level of viral replication. For children with high levels of viral replication, this regimen seems to be ineffective. PMID- 8006397 TI - Beneficial effect of prednisolone withdrawal followed by human lymphoblastoid interferon on the treatment of chronic type B hepatitis in Asians: a randomized controlled trial. AB - To evaluate the effect of interferon and the benefit of prednisolone pretreatment in Oriental patients with chronic active hepatitis B, 120 male Chinese patients were randomly allocated to receive: 1) group A: a 4-week course of prednisolone followed by 2 weeks of no treatment and then a 12-week course of human lymphoblastoid interferon, 4 to 6 MU/m2 intramuscularly; 2) group B: as group A, but with placebo given instead of prednisolone; 3) group C: an 18-week course of placebo. Clearance of serum hepatitis B virus-DNA and HBeAg (complete response) was achieved in 21% of group A, 5% of group B and none of group C at the end of therapy (A vs B: p = 0.054; A vs C: p < 0.01). When assessed 12 months after the end of therapy, the complete response rate was 46% in group A, 24% in group B and 25% in group C (p < 0.05). Those with baseline alanine transaminase < or = 200 U/l showed a better response to interferon following prednisolone withdrawal (48%) than with interferon therapy alone (20%, p = 0.056) and no treatment (9%, p < 0.01). Those with a baseline serum hepatitis B virus-DNA < or = 1000 pg/ml also showed a higher complete response rate when pretreated with prednisolone (59%) than when treated with interferon alone (29%, p = 0.084) or untreated (22%, p < 0.03). The strongest independent predictor of a response to treatment was prednisolone withdrawal (p < 0.05). None of the responders lost hepatitis B surface antigen.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8006396 TI - Efficacy of steroid withdrawal and low-dose interferon treatment in chronic active hepatitis B. Results of a randomized multicenter trial. Swiss Association for the Study of the Liver. AB - Fifty-six patients with biopsy-proven, chronic active hepatitis B were included in a multi-center, randomized trial comparing steroid withdrawal followed by 1.5 MU recombinant interferon alpha 2b (Intron) with placebo withdrawal followed by either 1.5 or 5 MU interferon. The patients were equally distributed between the treatment groups with respect to biochemical and histologic activity as well as with respect to DNA levels and quantitative liver function tests. One patient was lost to follow up. After 1 year of treatment, 10/18, 13/19 and 11/18 patients had lost hepatitis B virus DNA in the three groups, respectively (non-significant). Transaminase levels were normal in 27/34 of the responders but in only 4/21 of the non-responders (p < 0.0001). Both galactose elimination capacity and aminopyrine breath test improved significantly in responders, but either did not change (aminopyrine breath test) or deteriorated in non-responders (galactose elimination capacity). Biopsy score improved in both groups but this reached statistical significance only in responders. This effect was due to improvements in both inflammatory and fibrotic activity. Side effects included almost universally a flu-like syndrome, granulocytopenia (1), depression (3) and thyroid dysfunction (2). Two deaths occurred, one due to hepatocellular cancer, and the other to hepatorenal syndrome after spontaneous bacterial peritonitis. A severe cytolytic episode was observed in three patients in the steroid withdrawal group. We conclude that in patients with marked histologic activity, lower doses of interferon may be as effective as the standard dose of 5 MU.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8006398 TI - Antimitochondrial antibody profiles in patients with primary biliary cirrhosis before orthotopic liver transplantation and titres of antimitochondrial antibody subtypes after transplantation. AB - Four antimitochondrial antibody profiles (A-D) have been defined in primary biliary cirrhosis according to the presence of antibodies to M2, M4, M8, and M9 in ELISA and the complement fixation test: A: anti-M9 positive in ELISA and western blot, B: anti-M9 and/or anti-M2 positive in ELISA, C: anti-M2, -M4 and/or -M8 positive in ELISA, D: anti-M2, -M4, and/or -M8 positive in ELISA and complement fixation test. These profiles predict the outcome of primary biliary cirrhosis in the early stages and reflect differences in the natural course of the disease (benign versus progressive). In this study sera from 29 patients with advanced primary biliary cirrhosis who had received liver transplant were retested before and after orthotopic liver transplantation. Twenty-eight were antimitochondrial antibody/anti-M2 positive, and one patient had only antibodies to nuclear dots in the immunofluorescence test on cell cultures. When the antimitochondrial antibody-profiles in these 28 anti-M2 positive patients were analysed, it became evident that 26 of them belonged to subgroup C or D before orthotopic liver transplantation. Two patients had profile B; one had high titres of antinuclear and smooth muscle antibodies indicating an overlap syndrome between primary biliary cirrhosis and autoimmune chronic active hepatitis. The other patient had antibodies to nuclear dots in association with anti-M2. None of the patients had profile A. Antibody titres were studied after orthotopic liver transplantation in 23 of the 28 patients who survived for 1 to 13 years.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8006399 TI - Effect of perfusate pH on the influx of 5-5'-dimethyl-oxazolidine-2,4-dione and dissociation of epidermal growth factor from the cell-surface receptor: the existence of the proton diffusion barrier in the Disse space. AB - The influx clearance (PSinf.MID) of the weak acid 5,5'-dimethyl-oxazolidine-2,4 dione (DMO) was determined by the multiple indicator dilution method with the isolated perfused rat liver under various perfusate pH conditions, ranging from 6.4 to 7.6. Although the pH partition theory predicted an increase in influx clearance of ten times in proportion to the change in the unionized fraction of DMO, there was no measurable change in this value. The effect of medium pH on the steady-state cell/medium concentration ratio (C/M) ratio of DMO was also investigated using isolated hepatocytes. The C/M ratio increased while medium pH decreased, but this change was less marked than predicted by the pH partition theory. Finally the pH dependency of the dissociation rate constant (koff) of epidermal growth factor from its receptor was also investigated using both isolated rat hepatocytes and the perfused rat liver. When the extracellular pH was changed from 6.4 to 5.6, the koff value of isolated hepatocytes increased 44 times, while that of the perfused rat liver increased only 9 times. Therefore, the effect of changing the extracellular pH on pH-dependent dissociation of epidermal growth factor from its cell-surface receptor was less in the perfused liver than in isolated hepatocytes. These findings, in addition to the well-known existence of the Na(+)-H+ exchanger on the sinusoidal membrane and the possible existence of the unstirred water layer in the Disse space, seem to suggest the existence of the proton diffusion barrier in the rat liver, which remains stronger in the perfused liver than in isolated hepatocytes. PMID- 8006400 TI - High doses of aminoglycosides did not produce liver toxicity in patients with cystic fibrosis. AB - Liver disease is common in patients with cystic fibrosis, but the pathogenesis is poorly understood. The chronic colonization of bacteria in the lower airways leads to repeated treatments with antibiotics, especially aminoglycosides in high dosages. To investigate the possible role of aminoglycoside treatment in the natural history of liver disease in cystic fibrosis, five patients were studied for 3 years. Four of the patients received repeated courses of antibiotics, in two of the patients at the time of the liver biopsies. One patient did not receive any aminoglycosides. Light and electron microscopical morphometry was done on liver biopsy specimens. The contents of fat and lysosomes were quantified and expressed as volume density of liver cell volume (%). The amount of fat calculated in this way (13-35%) was highest in one patient who had not received any aminoglycosides. The two patients being treated with aminoglycosides at the time of the biopsy showed small amounts of fat in their liver cells (0.2-1.5%); similar values were noted in some patients who had not been treated for years. The lysosomes did not show the specific changes previously reported to occur in the kidney, nor did the morphometrical quantitation reveal any abnormalities which could be related to the administration of aminoglycosides. The present study did not find liver toxicity related to aminoglycosides in repeated high therapeutic dosages given to patients with cystic fibrosis. PMID- 8006401 TI - Terlipressin or vasopressin plus transdermal nitroglycerin in a treatment strategy for digestive bleeding in cirrhosis. A randomized clinical trial. Liver Study Group of V. Cervello Hospital. AB - Between 1988 and 1990 an unblinded, randomized trial of terlipressin or vasopressin plus transdermal nitroglycerin, as part of a treatment strategy including emergency sclerotherapy for actively bleeding varices, was conducted during 165 admissions in 137 patients with cirrhosis and upper digestive bleeding. Eighty-four patient admissions were assigned to terlipressin (2 mg every 6 h) and 81 to vasopressin (0.4 to 0.8 unit per min) plus transdermal nitroglycerin (20 to 80 mg). The two groups were comparable for relevant clinical data, but there were slightly more patients with hepatocellular carcinoma or terminal conditions in the terlipressin group. After the 24-h study period, failure to control bleeding was 20/84 (25%) in the vasopressin and 14/81 (17%) in the terlipressin group (p = 0.19). Corresponding figures for patients bleeding from varices (emergency sclerotherapy in 43 and 45, respectively) were 13/55 (24%) and 5/56 (9%; p = 0.035), from other sources 5/16 (31%) and 2/15 (13%; p = 0.23), from undefined sources 2/10 (20%) and 7/13 (54%; p = 0.1). In a logistic multivariate regression model the odds ratio for terlipressin adjusted for prognostic factors was 0.45 (p = 0.07). There were seven major side effects requiring treatment discontinuation in the vasopressin and one in the terlipressin group. These results suggest that terlipressin alone is as effective as vasopressin plus transdermal nitroglycerin, with less severe side effects, in 24-h control of upper gastrointestinal bleeding in patients with cirrhosis. PMID- 8006402 TI - Adenomatous hyperplasia of the liver in a patient with congenital hepatic fibrosis. AB - We report the case of a 30-year-old man suffering from congenital hepatic fibrosis, who was treated at age 12 by splenorenal shunt for portal hypertension, and who developed numerous, large hepatic nodules. The patient underwent liver transplantation because of recurrent episodes of acute cholangitis and the presence of foci of dysplasia in the nodules. Histological examination of the surgical specimen showed adenomatous hyperplastic nodules with a few atypical foci in an otherwise fibrous but non-cirrhotic liver. Such lesions have not yet been described in congenital hepatic fibrosis. The respective roles of congenital hepatic fibrosis and splenorenal shunts in the development of these nodules are discussed. PMID- 8006403 TI - Renal and hormonal responses to repeated treatment with enalapril in non-azotemic cirrhosis with ascites. AB - Since a single dose of the angiotensin-converting enzyme inhibitor enalapril was shown to cause natriuresis in cirrhosis in a previous study, we investigated whether repeated doses of this substance would sustain a favorable renal effect in cirrhosis. Ten milligrams of enalapril maleate were administered once a day for 8 days to ten patients with non-azotemic cirrhosis and ascites. Enalapril reduced blood pressure significantly at 4 to 12 h (systolic blood pressure) and 2, 6, and 8 h (diastolic blood pressure) on day 2, compared to pretreatment (day 0) values, but this depressor effect decreased on day 8. No change in heart rate could be detected. Enalapril significantly suppressed serum angiotensin converting enzyme activity and plasma aldosterone concentration (p < 0.001 to 0.01), which were elevated prior to treatment, with pretreatment values of 25.8 +/- 1.8 IU/l for serum angiotensin-converting enzyme activity and 241 +/- 67 pg/ml for plasma aldosterone concentration. This drug caused a 12 to 24% increase (p < 0.05 to 0.01) in mean daily urinary volume and a 40 to 54% increase (p < 0.001 to 0.01) in mean daily urinary sodium excretion from the respective pretreatment baselines during the 8-day period. Creatinine clearance was improved (p < 0.05) by the treatment, with mean improvement values from 24 to 34% above the pretreatment value of 47.4 +/- 4.3 ml/min.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8006404 TI - Effect of development on the functional and histological changes induced by bile duct ligation in the rat. AB - Secondary biliary cirrhosis in the rat can be induced by bile duct ligation; the aim of the present study was to investigate whether susceptibility to this injury depends on development. Rats aged 4, 7, 14 and 22 weeks were bile-duct ligated or sham operated. Four weeks later, stereologic analysis of the liver was performed and the volume fraction of parenchyma, bile ducts and connective tissue was determined. Microsomal function was assessed in vivo by the aminopyrine breath test and in vitro by determining the microsomal cytochrome P450 content and microsomal lipid composition. In addition, portal pressure was measured. The volume fraction of parenchyma decreased in an age-dependent fashion in bile-duct ligated rats from 64.0 +/- 11.2% in the youngest to 46.4 +/- 8.4% in the oldest age group. This decrease was compensated by an age-dependent increase in both ductular proliferation and fibrosis. Microsomal function both in vivo and in vitro showed an age-dependent deterioration. Microsomal cholesterol and some individual phospholipids showed age-dependent changes. Portal hypertension developed in all bile-duct ligated groups, but portal pressure was significantly lower in the oldest bile-duct ligated groups (16.0 +/- 2.6 cmH2O) compared with other bile-duct ligated groups (around 21 cmH2O). We conclude that susceptibility to the sequelae of chronic cholestasis depends on the stage of development in rats. In experiments using this model, the age of the rats should be explicitly stated. PMID- 8006405 TI - Is ursodeoxycholic acid an effective therapy for total parenteral nutrition related liver disease? AB - Cholestasis is the predominant complication in patients with total parenteral nutrition-related liver disease. Ursodeoxycholic acid has been reported to be beneficial for patients with various chronic cholestatic liver diseases. The aim of this prospective study was to determine the effects of short-term administration of ursodeoxycholic acid in nine patients (mean age 54 years) treated with home total parenteral nutrition (31 +/- 2 (mean +/- SEM) kcal/kg per day) for 13.9 +/- 5.2 months for short bowel syndrome; all presented biological evidence of hepatic cholestasis (mean alkaline phosphatase activity 5.2 times the upper limit of the normal) which appeared during nutrition; there was no cause of hepatic dysfunction other than total parenteral nutrition. Patients received 11.2 +/- 0.8 mg/kg per day of ursodeoxycholic acid orally for 1 (n = 9) or 2 (n = 5) 2 month periods, each of which was followed by a 2-month wash-out period. Liver function tests were performed before and at the end of each period. Compared with non-treatment periods, the two periods of ursodeoxycholic acid administration induced a significant reduction in gamma-glutamyl transpeptidase (27.1% and 20.4% respectively; p = 0.001) and alanine aminotransferase serum activities (7.0% and 34.8% respectively; p = 0.01) from baseline values. Alkaline phosphatase activity (p = 0.09), aspartate aminotransferase (p = 0.11) and bilirubin (p = 0.75) serum activities underwent no significant change during the study. These preliminary results strongly suggest that short-term ursodeoxycholic acid administration leads to biochemical improvement in liver function tests in patients with total parenteral nutrition-related liver disease. PMID- 8006406 TI - Soluble CD8 and soluble CD4 antigens in viral hepatitis and alcoholic cirrhosis. AB - Serum levels and production of soluble CD8 and soluble CD4 antigens by peripheral blood mononuclear cells were determined in patients with alcoholic cirrhosis and acute or chronic viral hepatitis. Patients with chronic viral hepatitis had significantly increased soluble CD8 serum levels (n = 18; 734 +/- 143 U/ml) (mean +/- SD) compared to healthy controls (n = 80; 312 +/- 141 U/ml; p < 0.001) and patients with alcoholic cirrhosis (n = 12; 505 +/- 256 U/ml; p = 0.006), whose soluble CD8 concentrations were also higher than controls (p < 0.001). In contrast, soluble CD4 antigen serum levels were similar in all groups. In addition, patients with chronic hepatitis showed an increased production of soluble CD8, but not soluble CD4, after mitogenic stimulation of their peripheral blood mononuclear cells compared to controls or patients with alcoholic cirrhosis. Patients with acute viral hepatitis, studied within the first 2 weeks after onset of jaundice, showed markedly elevated serum concentrations of soluble CD8 (n = 4; 807 +/- 379 U/ml; p < 0.001 vs. controls), but not soluble CD4. In addition, nine patients with chronic hepatitis C were studied during and after treatment with alpha interferon. Soluble CD8 serum concentrations of six treatment responders were not found to be different from the low levels seen in controls, whereas three non-responders had increased soluble CD8 levels which were similar to levels in untreated patients with chronic hepatitis C. After interferon-alpha therapy ended, a significant elevation of soluble CD8 serum concentrations was observed in four relapsing patients, which paralleled the serum ALT increase.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8006408 TI - Effect of clonidine on liver oxygen extraction during alcohol withdrawal in man. AB - Since catecholamines can alter splanchnic oxygen transport and extraction, the suppression of sympathetic overactivity during alcohol withdrawal might improve hepatic oxygen extraction. Therefore, this study investigated the effects of clonidine, a centrally-acting alpha 2-agonist which reduces sympathetic nervous outflow, on splanchnic oxygen transport and extraction in 13 patients with chronic alcoholism during alcohol withdrawal. All patients had elevated transaminases and steatosis at liver biopsy and were withdrawn from alcohol 51 +/ 15 h (mean +/- SD) before the study. Hepatic blood flow, cardiac output and the oxygen contents were measured in the radial and pulmonary arteries and in the hepatic veins before and 45 min after intravenous administration of clonidine, 150 micrograms. Basal hepatic blood flow was inversely correlated with norepinephrine plasma concentrations (r = -0.63, p < 0.025). After clonidine administration, the decrease in plasma norepinephrine correlated with the norepinephrine basal value (r = 0.889, p < 0.001), and splanchnic oxygen extraction increased (from 40 +/- 15 to 49 +/- 17%, p < 0.025). After clonidine administration, splanchnic oxygen extraction was correlated with the decrease in plasma norepinephrine (r = 0.72, p < 0.01). Arterial lactate concentration decreased (from 0.74 +/- 0.20 to 0.64 +/- 0.23 mmol/l, p < 0.01). These results suggest that defective liver oxygen extraction might occur during alcohol withdrawal as a result of sympathetic nervous hyperactivity. Alterations in the hepatic microcirculation during withdrawal might be related to catecholamine secretion and be controlled by pharmacological manipulation. PMID- 8006407 TI - Hepatitis C virus after interferon treatment has the variation in the hypervariable region of envelope 2 gene. AB - There is a hypervariable region in the envelope 2 gene of the hepatitis C virus genome, whose heterogeneity in different hepatitis C virus isolates has been suggested to be a result of the immune selection of escape variants. To determine the role of hypervariable region variants in the mechanism of resistance to interferon observed in 75-80% of interferon-treated patients with chronic hepatitis C, hypervariable region sequences were compared before and after interferon treatment. Eight patients with chronic hepatitis C were treated with recombinant interferon-alpha-2b. DNA containing the hypervariable region was obtained by reverse transcription-polymerase chain reaction from serial plasma samples of each patient and directly sequenced without cloning to determine changes in the predominant sequence. In two patients, hepatitis C virus-RNA was eliminated by interferon treatment. In the remaining six patients, hepatitis C virus-RNA was not eradicated. The predominant hepatitis C virus which survived interferon treatment was the mutant hepatitis C virus with 3-19 out of 81 nucleotide substitutions in the hypervariable region, resulting in 2-14 out of 27 amino acid changes. Most of the nucleotide substitutions were nonsynonymous, indicating that there were positive selections for amino acid changes in the hypervariable region. The change rate was significantly higher in patients whose plasma hepatitis C virus-RNA was consistently detectable during and after interferon treatment than in patients whose plasma hepatitis C virus-RNA became undetectable during treatment and reappeared after the cessation of the treatment (4.23 +/- 0.43 vs 0.77 +/- 0.20 x 10(-1)/site/year, p < 0.01). This suggests that the evolution of the hypervariable region was associated with the effect of interferon treatment. These results suggest that hypervariable region variants play an important role in maintaining persistent infection during interferon treatment by evading host immune surveillance. PMID- 8006409 TI - Ascites apheresis, concentration and reinfusion for the treatment of massive or refractory ascites in cirrhosis. AB - A new method for ascites recirculation, consisting of a cellulose diacetate filter to remove substances with molecular weight > or = 300,000, cell debris and bacteria, followed by the concentration of ascitic fluid prior to i.v. infusion, was used 24 times in 19 patients with cirrhosis and massive or refractory ascites. The amount of ascites removed was 7.67 +/- 0.49 l, which was reduced to 407 +/- 37 ml. The procedure took 367 +/- 22 min to complete. No statistically significant changes in liver function tests, coagulative parameters, platelet count or natremia were found. The activity of coagulation and fibrinolytic systems was further assessed in six patients. No changes suggesting an activation of intravascular coagulation and/or primary fibrinolysis were disclosed. An asymptomatic fall in mean arterial pressure (from 88.6 +/- 2.6 to 80.3 +/- 3.0 mmHg; p = 0.02) occurred after paracentesis and was still present 48 h after ascites reinfusion. Plasma renin activity significantly decreased at the end of the procedure, but was not associated with a proportional reduction of plasma aldosterone concentrations. Both variables returned to baseline values 48 h later. A significant increase in the glomerular filtration rate occurred just after the end of the procedure (from 50.4 +/- 9.1 to 73.1 +/- 23.5 ml/min; p < 0.05) and subsided 48 h later. In contrast, no significant changes in diuresis and renal sodium excretion were found. Complications due to volume overload and sepsis did not occur; in one case, spontaneous bacterial peritonitis developed 3 days after the procedure.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8006410 TI - The cell adhesion molecules of hepatic sinusoidal endothelial cells. PMID- 8006411 TI - Depressed phagocytic activity of Kupffer cells after warm ischemia-reperfusion of the liver. AB - Phagocytic activity of Kupffer cells following hepatic ischemia/reperfusion was studied in 39 livers of male Sprague-Dawley rats by in vivo fluorescence microscopy. Animals were subjected to either 20 min (group B, n = 9) and 60 min left hepatic lobar ischemia (group C, n = 9) or to 20 min of global hepatic ischemia (group D, n = 11). Sham-operated animals without ischemia served as controls (group A, n = 10). After 60 min postischemic reperfusion, fluorescent latex beads (3 x 10(8).kg body wt-1; diameter: 1.1 microns) were injected intra arterially. The zonal distribution and kinetics of adherence of latex beads were quantified by off-line video analysis. After 20 min of left hepatic lobar ischemia, 50%, 38% and 12% of injected latex beads adhered in zones 1, 2 and 3, respectively, and did not significantly differ from control livers (group A: 57%, 32% and 11%). In contrast, after 60 min of left hepatic lobar ischemia (group C) as well as after 20 min of global hepatic ischemia (group D), a more homogeneous distribution of latex beads adherent in zones 1, 2 and 3 was observed (group C: 48%, 36% and 16%; group D: 48%, 36% and 16%). Kinetic analysis of phagocytosis (% adherence of visible latex beads 1 min and 3 min after injection) showed no significant difference between 20 min left hepatic lobar ischemia (group B: 84% and 95%) and control (group A: 81% and 95%).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8006413 TI - The regenerative response in intact young livers grafted into different sized recipient pigs. PMID- 8006412 TI - Transient hepatofugal portal blood flow in alcoholic cirrhosis with acute alcoholic hepatitis. PMID- 8006415 TI - The Gay Identity Questionnaire: a brief measure of Homosexual Identity Formation. AB - This article describes the development of the Gay Identity Questionnaire (GIQ) which was derived from tenets of the Homosexual Identity Formation (HIF) model proposed by Cass in 1979. The GIQ is a brief measure that may be used by clinicians and researchers for identifying gay males in the various stages of homosexual identity formation. The test construction procedures included the selection of questionnaire items based upon constructs of the Homosexual Identity Formation Model, establishment of interrater and interitem reliability for those items, and refinement of the GIQ through two pilot tests. The final version of the GIQ was administered to two hundred twenty-five males who reported having same-sex fantasies or engaging in homosexual behavior. In addition, demographic and psychosocial data were collected and used to describe the sample and examine the relationship of these variables to subject stage of HIF. Results support the use of the Gay Identity Questionnaire as a brief measure for identifying subject stage of homosexual identity formation. The data also suggest that homosexual identity acquisition may be a two-stage process rather than the six-stage process proposed by Cass (1979). The differentiation between these stages includes whether or not a subject had resolved a coherent self-identity as gay and had a significant relationship to some aspect of the gay culture. PMID- 8006414 TI - Lipiodol computed tomography should be part of pre-operative assessment for liver transplantation. PMID- 8006416 TI - Gatekeeping through media format: strategies of voice for the HIV-positive via human interest news formats and organizations. AB - This research examines the extent to which HIV-positive voices are marginalized in the mainstream versus the "alternative" press. The central claim of this research is that news media format considerations, constructed around what has come to be called "media logic," leave persons who are HIV-positive with comparatively little voice in the mainstream press. By utilizing techniques of content analysis, the research examines 535 major HIV/AIDS-specific stories published in two oppositional papers toward an assessment of the level of HIV positive voice in each outlet. While arguments of "homophobia" have been previously used to explain bias in mainstream HIV/AIDS-coverage, this article asserts that "hetero-centric" bias is, in fact, embedded in the routinized practices of mainstream "news production." The article concludes by suggesting that successful future HIV/AIDS activism demands a recognition of "media logic" and an adoption of its tactics. PMID- 8006417 TI - Political tolerance of homosexuals: the role of group attitudes and legal principles. AB - Individuals' attitudes toward and acceptance of general legal principles were assessed along with their willingness to extend application of these principles to various social and political groups, including homosexuals. Respondents then indicated their attitudes toward various social and political groups, including the groups to whom they had applied the general principles. Regression analyses were used to determine to what degree acceptance of the general principle and attitude toward the social group predicted application of the general principle to the group. For disliked groups such as the Ku Klux Klan and Nazis, individuals' acceptance of the general principle alone predicted the specific application. For homosexuals, however, the application of the general principle was affected both by acceptance of the general principle and by individuals' attitudes toward homosexuals. The implications of this difference in light of research addressing the cognitive and affective nature of attitudes and attitude change is discussed. PMID- 8006418 TI - Chicken kills hawk: gay murders during the eighties in Amsterdam. AB - A relatively large number of murders in Amsterdam are of older homosexual men. Police records and personality reports by social workers for the decade of the 1980s were investigated and interviews of "potential victims" were conducted in order to study why the crimes were committed. It was found that the murderers were mostly young male prostitutes. The evidence suggests that the motive for such crimes is usually complex and is influenced by the marginal social situation of the two groups involved, in which the lack of emotional and financial support plays a large role. PMID- 8006419 TI - Dating scripts of gay men and lesbians. AB - Scripts for a first date for 51 gay men and 44 lesbians were explored. Well defined scripts were found for both hypothetical and actual accounts. Hypothetical scripts contained fourteen actions for gay men and lesbians; eleven were common to both. Gay men's actual scripts had eighteen actions and lesbians' had nineteen, with twelve common to both. Gay men's scripts were more sexually oriented and less intimacy-focused than lesbians'. However, scripts for both genders were free of many other aspects of traditional heterosexual roles and involved some actions unique to this population. PMID- 8006420 TI - Medieval Arabic medical views on male homosexuality. AB - Medieval medical views on homosexuality are outlined. Three theories seem to have been present. The first considers homosexuality as a nasty psychological phenomenon that ought to be punished rather than treated. The second theory suggests that an abnormal sensory innervation to the penis requires intense sensory input to achieve sexual satisfaction. A third congenital theory proposes that homosexuality results when the maternal sperm prevails over the paternal sperm. The most important proponent of the first theory was Avicenna (Ibn-Sina, 980-1037 A.D.); a literal translation of the relevant chapter from his Canon of Medicine is given. PMID- 8006421 TI - "That matter which ought not to be heard of": homophobic slurs in Renaissance cultural politics. AB - Starting with a poem for which the Reformed theologian Theodore de Beze was attacked as a sodomite, this essay studies the nature of homophobic slurs leveled by Catholics against Protestants and by Protestants against Catholics in the period following the Reformation. More than just incidental attacks, slurs by such writers as Henri Estienne, John Bale, and John Jewel are found to be an integral part of a mythology that validated Protestantism in general and the English church in particular. But occasionally they are also used by Catholics as, for instance, by Jerome Bolsec against Beze and Gaspar Schoppe against King James I. Largely ignored by church historians, such slurs are shown to be part of an archaeology of homophobia. PMID- 8006422 TI - Homosexuality in the early novels of Nageeb Mahfouz. AB - Nageeb Mahfouz is the earliest novelist in Arabic to focus on the homosexual protagonist in his writing. Although the topic is objectionable in Islam, Mahfouz explores homosexuality in a sensitive manner, and reveals the transformation in his views regarding the dilemma of the homosexual protagonist in a hostile environment. PMID- 8006423 TI - Integration of one's religion and homosexuality: a weapon against internalized homophobia? AB - Internalized homophobia as a psychological phenomenon has attracted little systematic research despite its destructive impact on the mental health of the gay community. This study looks at the relationship between internalized homophobia and the process of integrating one's religious faith and homosexuality by comparing levels of internalized homophobia among male participants of Dignity, an organization of Catholic gay men and lesbians, with a community sample of gay men with Catholic backgrounds. While many gay men believe they must abandon their religious faith (nearly 50% of this community sample no longer endorse a "formal religion") in order to accept their sexuality, Dignity members are actively integrating their religion and homosexuality--a process which we hypothesized would result in the Dignity participants being less homophobic than the community sample. While results showed no significant differences between the groups with regard to level of internalized homophobia, there are suggestions that involvement in Dignity does foster positive attitudes towards one's homosexuality by helping to overcome a delay in the development of a gay orientation. We also examined how other variables such as HIV status, psychological distress, conservative versus liberal ideology, and integration into the gay community would be associated with internalized homophobia. PMID- 8006424 TI - [Application of heat by microwaves and laser into the prostate]. PMID- 8006425 TI - [Effects of high-intensity focused ultrasound on the human prostate]. PMID- 8006426 TI - Occurrence of cutaneous basal cell and squamous cell malignancies among those with a prior history of skin cancer. The Skin Cancer Prevention Study Group. AB - Non-melanoma skin cancer patients are believed to be at high risk of developing new skin malignancies; however, relatively few studies have actually examined this. Non-melanoma skin cancers, although generally not fatal, are responsible for significant morbidity and, if left untreated, can cause serious disfigurement and, in rare instances, death. Part of the difficulty in studying these tumors is that they are not routinely followed as rigorously as other cancers, and are excluded from most cancer registries. Prior studies have often included patients from a single dermatology practice of those treated with one type of therapy (e.g., Moh's surgery). Some studies did not entail active follow-up of patients but relied on reports to a registry or subsequent visits initiated by the patient or their physician. Other studies have been based solely on patients with complete follow-up information, excluding those who died or were lost to follow up. Nearly all studies collected only a limited amount of information on each patient. In an attempt to overcome these limitations, we examined subsequent skin cancer occurrence among a group of patients followed as part of the Skin Cancer Prevention Study. In the following, we highlight some of the methodologic issues concerning the study of subsequent basal cell and squamous cell skin cancer risk, and the contribution of our work, along with that of others, in exploring clinical and etiologic questions pertaining to the occurrence of these malignancies. PMID- 8006427 TI - Epidemiology of psoriasis: clinical issues. AB - Psoriasis is a genetically inherited spectrum of skin diseases characterized by epidermal proliferation and inflammation, which are reversible. Although many have reported that psoriasis is triggered by trauma, infections, stress, drugs, etc., the epidemiology of psoriasis remains poorly understood. Linkage to human leukocyte antigen-(HLA)-Cw6 and DR7 is strong in people with early onset disease, but concordance in monozygotic twins is only 67%, emphasizing the importance of a triggering event. Other factors that have been reported to affect the course of psoriasis include upper respiratory infections, smoking, obesity, alcohol ingestion, regional enteritis, and human immunodeficiency virus infection. This manuscript reviews the clinical epidemiology of psoriasis and highlights some of the needs for further investigation into specific areas of the disease. PMID- 8006428 TI - Analytic epidemiology in psoriasis. AB - The cause of psoriasis has only recently been subject to structured epidemiologic research approach. This is reflected in the scarcity of quantitative knowledge about etiologic factors for psoriasis other than genetics. A schematic model suggests that susceptibility to develop psoriatic lesions includes both genetic and extragenetic predisposing factors. Expression in terms of visible lesions is modulated by precipitating or trigger factors. Unlike many chronic diseases, psoriasis spontaneously waxes and wanes. When assessing factors that trigger the onset of the disease, one must also consider factors that lead to recurrence or exacerbation. Cohort and case-control studies are the main methodologic options for risk assessment. Combination of these techniques and the merging of an epidemiologic approach with basic biologic research are suggested routes to valuable results in this area. PMID- 8006430 TI - The spectrum of Stevens-Johnson syndrome and toxic epidermal necrolysis: a clinical classification. AB - The nosology of severe bullous erythema multiforme (EM), Stevens-Johnson syndrome (SJS), and toxic epidermal necrolysis (TEN) remains controversial. To conduct a prospective case-control study of the etiologic factors of these diseases, we needed to define criteria for classifying the cases. After having reviewed photographs of the skin lesions of more than 200 patients, an international group of dermatologists proposed a classification based on the pattern of "EM-like lesions" (categorized as typical targets, raised or flat atypical targets, and purpuric macules) and on the extent of epidermal detachment. The "consensus" classification in five categories was as follows: bullous erythema multiforme, detachment below 10% of the body surface area (BSA) plus localized typical targets or raised atypical targets; SJS, detachment below 10% of the BSA plus widespread erythematous or purpuric macules or flat atypical targets; overlap SJSTEN, detachment between 10% and 30% of the BSA plus widespread purpuric macules or flat atypical targets; TEN with spots, detachment above 30% of the BSA plus wide-spread purpuric macules or flat atypical targets; TEN without spots, detachment above 10% of the BSA with large epidermal sheets and without any purpuric macules or target. Whether all five categories proposed represent distinct etiopathologic entities will require further epidemiologic and laboratory investigations. PMID- 8006429 TI - Epidemiology and the genetics of psoriasis. AB - Several lines of compelling epidemiologic evidence indicate that susceptibility to psorasis is inherited, albeit not in a simple monogenic fashion. Psoriasis is one of a number of diseases with a presumed autoimmune pathogenesis that display significant human leukocyte antigen (HLA) associations. However, only a small fraction of those who carry the implicated HLA susceptibility alleles develop disease. Taken together with the epidemiologic data indicative of high heritability, this observations suggests that one or more loci in addition to HLA are necessary for the development of psoriasis. As the identity of these other genes is unknown, genetic linkage analysis offers an attractive strategy for their identification. To this end, we have initiated a large linkage study of multiplex psoriasis kindreds, and PCR-based genotyping of CA repeat polymorphisms has been performed for several markers in the HLA region (6p21.3). As expected given the hypothesis of oligogenic inheritance, these analyses have thus far failed to reveal tight linkage of psoriasis to the 6p21 region. Nevertheless, the substantial homogeneity of the psoriatric phenotype and the clear evidence for increased HLA association and heritability in juvenile onset disease (40 years) indicate that, like insulin-dependent diabetes mellitus, psoriasis is an HLA associated, genetically complex disease whose etiology is potentially amenable to elucidation through linkage analysis. PMID- 8006431 TI - Epidemiologic approaches to the study of toxic epidermal necrolysis. AB - The appropriate epidemiologic strategy for studying the etiology of toxic epidermal necrolysis is determined by the characteristics of the disease, particularly its rarity and the fact that it is caused by numerous drugs. Although information about drugs as risk factors can in principal be obtained from case reports and experimental studies, the former are subject to bias and the latter are impractical because toxic epidermal necrolysis is so rare. Cohort studies are also impractical because of the rarity of the outcome. An automated database, even if based on a large population, can only yield valid results if it is used as the starting point for a case-control study that includes access to the subjects and to the medical records for information to confirm the diagnosis. A population-based case registry can provide a large enough and well-documented series of cases, but does not allow for the valid estimation of risks because it lacks a comparison series. This leaves a case-control study as the only strategy that is both practical and valid. An ongoing international case-control study of toxic epidermal necrolysis and Stevens-Johnson syndrome in relation to the use of drugs is described. Data collection has proceeded in France, Italy, Germany, and Portugal. The study in Germany is conducted within a population-based case registry, and the study in Portugal is also population based; this will allow for the estimation of absolute risks. Data on demographic factors and medical history, a detailed history of drug use in the month before hospital admission, and various other factors are collected by interview of the cases and hospital controls. Cases are confirmed in an independent review process in which the diagnoses, and classification along a spectrum of Stevens-Johnson syndrome and toxic epidermal necrolysis, are determined without knowledge of drug use. As of June, 1993, 459 cases and 1299 controls have been enrolled. At the scheduled end of data collection in 1995, the projected totals are 691 cases and 1956 controls. These large numbers will allow for the detailed evaluation of even relatively uncommonly used drugs, for the evaluation of more commonly used drugs in relation to subtypes of toxic epidermal necrolysis/Stevens-Johnson syndrome, and for the comparison of results between countries. PMID- 8006432 TI - Epidemiology of skin disease in HIV infection: a cohort study of health maintenance organization members. AB - The medical literature suggests that persons infected with human immunodeficiency virus (HIV) have an increased risk of many common and uncommon cutaneous diseases. Further, it has been suggested that in HIV-infected people these conditions may be more persistent and they may be more prone to developing adverse cutaneous reactions to drugs. We have identified a cohort of 684 HIV infected persons who were members of a large Massachusetts health maintenance organization. Based on review of hospital records, automated ambulatory records, and automated prescription data for these patients, we determined the occurrence of skin disease including adverse reactions to drugs. In this 2.8-year study, these HIV-infected persons averaged 3.7 separate skin diagnoses each, a significantly higher rate (p < 0.001) than in a comparable uninfected group of enrollees in this health maintenance organization. The rate of visits for many common skin diagnoses increased as HIV infection progressed. Cutaneous drug reactions were also significantly more frequent (per course of drug) in AIDS patients compared to patients with asymptomatic HIV infection. Skin disease is a frequent and important cause of morbidity in HIV-infected persons. The development of a specific cutaneous disease may act as a prognostic marker for progression of HIV infection. In HIV-infected persons, adverse cutaneous reactions to drugs frequently limit treatment with essential drugs. PMID- 8006433 TI - Chronic cutaneous ulcers: etiology and epidemiology. AB - The most commonly encountered chronic cutaneous ulcers in the United States are pressure ulcers and leg ulcers; this review is limited to the epidemiology of these ulcers. Chronic leg ulcers are frequently encountered in clinical practice but the extent of the problem is largely unknown. In particular, epidemiologic information within the United States is sadly lacking. Although there are more data available regarding the incidence and prevalence of pressure ulcers in acute and chronic care facilities, national surveys should be considered to obtain more accurate information on their incidence and prevalence. Multicenter studies are necessary to determine the epidemiology and cost of treating pressure ulcers by stage, setting, and other factors. Particular attention should be paid to high risk groups such as spinal cord injury patients, the elderly, and those who are immobilized or chronically debilitated. Leg ulcers and pressure ulcers probably account for the majority of chronic cutaneous ulcers seen in the United States. PMID- 8006434 TI - Epidemiology of nonmelanoma skin cancer: clinical issues, definitions, and classification. AB - There are many forms of nonmelanoma skin cancer, although the term usually refers to the most common forms, basal and squamous cell carcinomas of the skin. The definitions of basal and squamous carcinomas depend on histopathologic features, and clinical diagnoses are often reliable. Various classification schemes have been proposed, including those based on clinical or histologic appearance, etiology, or prognosis. The public health burden of these tumors has not been fully defined and includes mortality, morbidity, social impact, and cost. Measures of morbidity include incidence and measures of impairment, disability, and handicap. Other issues involving etiology, management, prevention, and early detection remain to be investigated further. PMID- 8006435 TI - Correlates of pressure sores in nursing homes: evidence from the National Medical Expenditure Survey. AB - Pressure sores are a serious medical problem that is most commonly found in nursing homes and hospitals. Most sores can be prevented. To prevent pressure sores in nursing homes through intervention, it is first necessary to identify factors associated with sore formation. Factors associated with the formation of pressure sores relate to skin susceptibility combined with the presence of moisture, constant pressure, and shear force or friction on the skin. This paper is the first to study the correlates of pressure sores for a nationally representative sample of nursing home residents. The paper estimates the relative contribution of resident health characteristics to the probability of having had a pressure sore during a nursing home stay for a cross-sectional sample of residents. Data are from 699 facilities and 2803 residents in nursing homes included in the 1987 Institutional Population Component of the National Medical Expenditure Survey. The principal caregiver in the facility was asked if "during the current stay" the resident had a "bed sore (decubitus ulcer)." Findings indicate that having diagnoses of Parkinson's disease, diabetes, or paraplegia, being underweight, older, male, unable to walk, needing help feeding or unable to feed, having frequent fecal and urinary incontinence accidents, and being admitted from a hospital increase the likelihood of having had a pressure sore during the stay. Cognitively impaired residents who could feed themselves independently or with help were less likely to have had a sore, but cognitively impaired residents who were unable to feed themselves at all were at more risk than cognitively intact residents. PMID- 8006436 TI - Genetic epidemiologic studies in the etiology of skin diseases. AB - Genetic epidemiologic studies have provided critical insights into the etiology of both rare and common skin diseases. Designs for these studies are distinct from those generally employed in epidemiologic studies. Here, we review the types of data collected for various genetic epidemiologic designs, inherent strengths and weaknesses, and their similarities to more classic epidemiologic methods. Examples from the study of skin diseases are provided to highlight the successful application of these methods. PMID- 8006437 TI - The genetics of ichthyosis: a primer for epidemiologists. PMID- 8006439 TI - The National Epidermolysis Bullosa Registry. AB - Since its inception in 1986, the NEBR has proved to be an excellent example of how a relatively small allocation of federal research funds for the development of a registry of cases of a single rare disease can have a major impact on the rapid expansion in the depth of knowledge of not only the disease itself but of a number of associated biologic principles, including keratinization and epithelial cell-extracellular matrix interactions. At present, the NEBR is generating extensive clinical, laboratory, and demographic data, both from cross-sectional and longitudinal perspectives, as well as establishing a centralized cell and tissue bank that will serve the scientific community at large as a valuable resource for future basic research on this oftentimes devastating genetic disease. PMID- 8006438 TI - Data resources for epidemiology of skin diseases. AB - Among existing data sets the First National Health and Nutrition Examination Survey (NHANES-I) stands out for its large sample size and detailed examination of the skin. However, because NHANES-I employed many different examiners and no uniform diagnostic criteria, the quality of the data is variable. Furthermore, the survey was conducted in the 1970s and does not contain information necessary to answer some currently relevant epidemiologic questions. Future data collection efforts will have to be planned to address specific hypotheses. In addition, future dermato-epidemiologic studies will have to pay careful attention to diagnostic accuracy. PMID- 8006440 TI - Opportunities for research in dermatologic epidemiology. AB - This report is based on a number of papers presented at the March 1993 Scientific Workshop on the Epidemiology of Skin Diseases, sponsored by the National Institute of Arthritis and Musculoskeletal and Skin Diseases. It focuses on opportunities in dermatologic epidemiology identified at the workshop and discusses these opportunities in the context of health maintenance organizations as sites for data collection, problems to be expected, and the potential contribution of dermatologic epidemiology. PMID- 8006441 TI - Epidemiologic investigation of nonmelanoma skin cancer mortality: the Rhode Island Follow-Back Study. AB - The Rhode Island Follow-Back Study was initiated to elucidate the magnitude and characteristics of nonmelanoma skin cancer mortality. All deaths reported among Rhode Island residents during 1979 through 1987 and attributed to nonmelanoma skin cancer were investigated and medical records sought. Most were misclassified, primarily due to squamous cell carcinoma of mucosal surfaces in the head and neck. In Rhode Island and nationally, this source of misclassification is increasingly frequent. Appropriate adjustment of national statistics for misclassification reveals a consistent decline in nonmelanoma skin cancer mortality rates from 1969 through 1988, although the actual numbers of deaths are increasing due to growth and aging of the population. Examination of the records of those Rhode Island residents who did die from nonmelanoma skin cancer demonstrated that most had squamous cell carcinoma, and many of those arose from the ear. These analyses suggest that particular emphasis should be placed on the ear in public health campaigns geared toward the prevention and early detection of nonmelanoma skin cancer. PMID- 8006442 TI - Genetic linkage mapping of heritable skin diseases: positional cloning versus the candidate gene approach. PMID- 8006443 TI - The autoantibodies of neonatal lupus erythematosus. PMID- 8006444 TI - Th1-Th2 paradigm: insights from leprosy. AB - The mechanism by which T cells and cytokines regulate immune processes in skin can be investigated by studying patients with leprosy. The disease, caused by the obligate intracellular bacterium Mycobacterium leprae, forms a spectrum. At one pole, patients with tuberculoid leprosy are able to restrict the growth of the pathogen and their skin lesions are characterized by a predominance of CD4+ T cells and type 1 cytokines including interleukin 2 and interferon gamma. At the opposite pole, patients with lepromatous leprosy are unable to contain the infection and their skin lesions are characterized by a predominance of CD8+ T cells and type 2 cytokines including interleukins 4 and 10. A key determinant of the T-cell cytokine response may be interleukin 12, which selectively favors expansion of CD4+ T cells producing interferon gamma. By understanding the factors that regulate T-cell and cytokine responses in leprosy, it should be possible to devise specific immunologic interventions in diseases of skin. PMID- 8006445 TI - Interleukin-7 induces differential lymphokine-activated killer cell activity against human melanoma cells, keratinocytes, and endothelial cells. AB - To assess the potential role of interleukin (IL)-7 in immunotherapy of human malignant melanoma, we have examined the lymphokine-activated killer (LAK) cell sensitivity of four human melanoma cell lines against LAK cells generated by IL-7 or IL-2. Lysis was determined by a 24-h cytotoxicity test using 3-[4,5 dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT). All melanoma cell lines were susceptible to IL-7- and IL-2-generated LAK cells. The sensitivity of melanoma cells to IL-2-induced LAK cells was higher compared to IL-7-induced LAK cells. At an effector target ratio of 20:1, the lysis by IL-7-induced LAK cells ranged between 41% and 52%, whereas IL-2-induced lysis ranged between 80% and 94% (p < 0.01). IL-7-induced LAK cells, however, showed almost no cytotoxicity towards HaCat keratinocytes and human umbilical vein endothelial cells (HUVECs). Immunophenotyping revealed a higher expression of the tac antigen (CD 25) on IL-7 generated LAK cells, particularly those cells that were CD 56 negative or CD 3 positive compared to IL-2-induced LAK cells. In contrast, IL-2-generated LAK cells killed 62% of the HaCat keratinocytes and 60% of the HUVECs. Secretion of tumor necrosis factor-alpha into culture supernatants was significantly higher in IL-2-generated LAK cells compared to IL-7-stimulated LAK cells (p < 0.01), whereas TNF-alpha levels of IL-7-induced LAK cells were in the range of unstimulated lymphocytes. Because nonspecific cytotoxicity against other normal cells such as keratinocytes and endothelial cells contributes to the dose limiting side effects of immunotherapy with IL-2, immunotherapy using IL-7 might be a better tolerated future alternative. PMID- 8006446 TI - IL-4 induces chemotaxis of blood eosinophils from atopic dermatitis patients, but not from normal individuals. AB - T lymphocytes present in allergically inflamed tissue synthesize and secrete the cytokines interleukin (IL)-3, IL-4, IL-5, and granulocyte/macrophage colony stimulating factor (GM-CSF). IL-3, IL-5, and GM-CSF, but also IL-4, may act as a chemotaxin on eosinophils. In contrast to the former cytokines, IL-4 is only chemotactic for eosinophils from the peripheral blood of patients with atopic dermatitis and not for eosinophils from normal individuals. IL-4 has the same chemotactic potency as the other cytokines. The optimal chemotactic potency is reached at a concentration of 10 nM. In contrast, neutrophils do not respond chemotactically to IL-4. Checkerboard analysis, inhibition studies with monoclonal anti-IL-4 antibodies, and desensitization experiments indicated specific interaction of IL-4 with eosinophils. In eosinophils from normal individuals, IL-4 responsiveness could be induced by pretreatment of the cells with IL-5 and GM-CSF. In addition to the fact that IL-4 may be responsible for selective eosinophil transendothelial migration, IL-4 may exert an important modulatory mode of action on eosinophil migration and function within allergically inflamed tissue. Our findings suggest the presence of a functional IL-4R on eosinophils from atopic dermatitis patients. PMID- 8006447 TI - Alopecia areata in aging C3H/HeJ mice. AB - A disease closely resembling human alopecia areata was found in a large production colony of C3H/HeJ mice that had no evidence of thyroid dysfunction or an infectious etiology. Alopecia developed diffusely or in circular areas on the dorsal surface. Histologically, the changes in this non-scarring alopecia were limited to anagen follicles that were surrounded by mononuclear cells. This infiltrate, composed primarily of cytotoxic (CD8+) and helper (CD4+) T cells, was associated with follicular and hair shaft dystrophy. This infiltrate was markedly reduced by intralesional injection of triamcinolone acetonide with subsequent hair regrowth in the affected site. Pedigree tracing of affected C3H/HeJ mice suggests that this non-scarring alopecia may be an inherited disease. Breeding results of normal haired mice with alopecia areata mice or between alopecia areata mice suggests that this is a complex polygenic disease with a female predominance at younger ages. Female mice developed the disease earlier than male mice (3-5 versus > 6 months), with equal numbers affected by 18 months of age. The relative incidence of alopecia areata in one production colony of C3H/HeJ mice was 0.25% for female and 0.035% for male mice, but selective breeding has raised the frequency to nearly 20%. The frequency in an aging colony selectively bred for inflammatory bowel disease reached 4.7%, with equal sex distribution, for mice over 18 months of age, suggesting that this might be a common aging change in C3H/HeJ mice. This C3H/HeJ mouse disease may prove to be a valuable animal model to study specific subtypes of human alopecia areata. PMID- 8006448 TI - Effects of insulin and insulin-like growth factors on cultured human hair follicles: IGF-I at physiologic concentrations is an important regulator of hair follicle growth in vitro. AB - Insulin stimulated hair follicle growth in a dose-dependent manner over the range of 0.01 to 100 micrograms/ml. Maximum rates of hair follicle growth were observed when follicles were maintained in medium containing 10 micrograms/ml insulin, which is supraphysiologic. Hair follicles maintained in the absence of insulin or at physiologic levels showed premature entry into a catagen-like state. Insulin like growth factor (IGF)-I and -II had no significant effect on hair follicle growth when maintained in the presence of 10 micrograms/ml insulin. However, in the absence of insulin, both IGF-I (0.01-100 ng/ml) and IGF-II (0.01-100 ng/ml) stimulated hair follicle growth in a dose-dependent manner. IGF-I was more potent than either insulin or IGF-II, stimulating maximum rates of hair follicle growth at 10 ng/ml, whereas IGF-II gave maximum stimulation at 100 ng/ml. The rates of hair follicle growth stimulated by 10 ng/ml IGF-I were identical to those stimulated by 10 micrograms/ml insulin. IGF-II (100 ng/ml), however, was unable to stimulate hair follicle growth to the same extent as insulin. Both IGF-I (10 ng/ml) and IGF-II (100 ng/ml) were more potent than insulin at preventing hair follicles from entering into a catagen-like state. Growth hormone had no effect on hair follicle growth or morphology in the absence of insulin. These data suggest that in vitro IGF-I may be an important physiologic regulator of hair growth and possibly the hair growth cycle. Moreover, the removal of insulin from tissue culture medium may be a useful method of generating large numbers of catagen hair follicles for further in vitro studies. PMID- 8006449 TI - Melanogenesis during the anagen-catagen-telogen transformation of the murine hair cycle. AB - Melanin synthesis of follicular melanocytes is strictly coupled to the growth stage of the hair cycle (anagen), ceases during follicle regression (catagen), and is absent throughout the resting stage (telogen). Having previously characterized the expression and activity of melanogenesis-related proteins during the telogen-anagen transition of the murine hair cycle (JID 96:172, 1991), we here report a biophysical and biochemical analysis of follicular melanogenesis during the anagen-catagen-telogen transformation of the C57 BL-6 mouse hair cycle. Tyrosinase activity and concentration as well as dopachrome tautomerase activity were compared with melanin synthesis, as measured by electron paramagnetic resonance spectroscopy (EPR). The visible changes in skin color and the histologically appreciable switch-off of melanin formation during the anagen catagen transformation were accompanied by a steep decline in 1) the melanin associated EPR signal of full-thickness mouse skin, 2) tyrosinase and dopachrome tautomerase activities, and 3) the skin concentration of 80-85-kD melanogenesis related protein and 66-68-kD tyrosinase protein. Telogen skin displayed a minimum of the EPR amplitude as well as of tyrosinase and dopachrome tautomerase activity detected. By EPR, only eumelanin was identified during all hair cycle stages. The gradual switch-off of melanogenesis during anagen VI started with an unexpectedly early decline of the EPR melanin signal, followed by dopachrome tautomerase activity and the concentration of 80-85-kD melanogenesis related protein. The initiation of catagen was characterized by a significant and rapid decrease in activity and concentration of tyrosinase, and was accompanied by a second drop in dopachrome tautomerase activity. Together, these biochemical and biophysical parameters of follicular melanogenesis serve as novel and differential markers for the imminent termination of anagen and the development of catagen. They also show that the switch-off of melanogenesis during the anagen-catagen-telogen transition is a stochastic process commencing already in mid anagen VI. PMID- 8006450 TI - Cadherin function is required for human keratinocytes to assemble desmosomes and stratify in response to calcium. AB - Elevation of the calcium concentration in keratinocyte culture induces the rapid organization of adherens junctions and desmosomes. Formation of these intercellular junctions is accompanied by reorganization of the cytoskeleton and, with a more delayed timecourse, stratification of the culture into a multilayered epithelial cell sheet. Keratinocytes express two cadherins, known as E- and P cadherin, which are the cell-cell adhesion molecules of the adherens junction. Antibody that blocks E-cadherin function delays the calcium-induced formation of both adherens junctions and desmosomes and leads to an abnormally stratified cultured. In the present study, we show that anti-E-cadherin plus anti-P-cadherin antibodies inhibit the formation of adherens junctions and desmosomes, prevent reorganization of the cytoskeleton, and block stratification. These studies indicate that cadherin function is required for the calcium-induced intercellular junction organization and stratification of human keratinocytes in vitro. PMID- 8006451 TI - Pemphigus foliaceus sera recognize an N-terminal fragment of bovine desmoglein 1. AB - It has previously been demonstrated that sera from endemic and nonendemic pemphigus foliaceus patients recognize three immunoreactive fragments of 80, 62, and 45 kilodaltons (kD) from extracts of the envelope fraction of human and bovine epidermis. These polypeptides are also immunoprecipitated by approximately 50% of pemphigus vulgaris sera, but are unreactive with sera from bullous pemphigoid patients or normal controls. The 80-kDa antigen has been shown to be a glycoprotein with N-linked oligosaccharides. Complete removal of the carbohydrate moieties produced a 76-kD polypeptide that continued to react with pemphigus foliaceus autoantibodies in a Ca(++)-dependent manner. To further characterize this antigen/antibody system, the 80-kD pemphigus foliaceus antigen solubilized from a bovine epidermal envelope extract was purified by affinity chromatography using a pemphigus foliaceus patient's immunoglobulin (Ig)G immobilized on agarose. After elution with 0.2 M glycine/HCl, pH 2.8, 5 mM ethylene diaminetetraacetic acid, the polypeptide was mixed with a small amount of 125I labeled 80-kD antigen, added as a tracer, fractionated by sodium dodecylsulfate polyacrylamide gel electrophoresis, and electrotransferred onto a polyvinylidene difluoride membrane. The 80-kD band detected by amido black staining and autoradiography was excised and characterized by amino acid sequence analysis. The resulting sequence, EXIKFAAAXREGEXNSKRNPIA, matched perfectly with the N terminal 22 amino acids of the mature form of bovine desmoglein 1. These findings demonstrate that the 80-kD bovine autoantibody-reactive polypeptide is the glycosylated ectodomain of desmoglein 1, which may contain epitopes recognized by pathogenic autoantibodies. PMID- 8006452 TI - Dibutyryl cyclic AMP modulates keratinocyte migration without alteration of integrin expression. AB - Cyclic adenosine monophosphate (cAMP) has long been regarded as a second messenger and a regulator of human keratinocyte proliferation. It has been demonstrated that cAMP inhibits keratinocyte proliferation when used at high concentrations. Nevertheless, new recent reports have demonstrated that cAMP may stimulate or inhibit keratinocyte growth depending upon the concentration used. Studies to examine the influence of cAMP upon the migration of other cell types have been contradictory. To determine the direct effect of dibutyryl cAMP (DBcAMP) upon human keratinocyte migration, we used a quantitative locomotion assay using a wide range of DBcAMP concentrations. We found a bi-phasic effect of DBcAMP on keratinocyte migration across connective tissue matrices. Keratinocyte locomotion on the matrices was promoted at 10(-5) M and 10(-6) M of DBcAMP, but not at higher or lower concentrations. Time-course experiments demonstrated that the effect of DBcAMP on keratinocyte locomotion and proliferation occurred independently. Fluorescence-activated cell sorter analysis demonstrated that the effect of DBcAMP on the migration of human keratinocytes was independent from the modulation of integrin receptors. Although the cellular mechanisms by which DBcAMP promotes keratinocyte migration is unclear, the addition of DBcAMP or TPA to keratinocyte cultures enhanced the synthesis of a 92-kDa metalloproteinase in association with enhanced cellular migration. These observations suggest a possible link between metalloproteinase expression and cellular migration. PMID- 8006453 TI - Differential effects of interleukin 1-alpha (IL-1 alpha) or tumor necrosis factor alpha (TNF-alpha) on motility of human melanoma cell lines on fibronectin. AB - Interleukin-1 alpha (IL-1 alpha) and tumor necrosis factor-alpha (TNF-alpha) induce a motogenic response in a number of benign and malignant cells. We examined the chemokinetic effects of these cytokines on the cell migration of four melanoma cell lines on fibronectin using modified Boyden chambers and video time lapse analysis. Flow cytometry analysis of IL-1 receptors, TNF receptors, and shifts in beta 1 integrin expression were correlated with the effects of these cytokines on cell migration on fibronectin. The four melanoma cell lines exhibited heterogeneous expression of types I and II IL-1 receptors as well as p60 TNF receptors. Scant p80 TNF receptor expression was detected on only one cell line. Three of four melanoma cell lines demonstrated type I IL-1 receptors by Western blotting. IL-1 alpha and TNF-alpha induced heterogeneous modulation of beta 1 integrin expression in the four melanoma cell lines tested; downward shift of the alpha 2, alpha 3, alpha 4, and beta 1 integrin subunits was detected among three of the melanoma cell lines as were upward shifts of the alpha 4, alpha 5, and alpha 6 integrin subunits among three of the melanoma cell lines. IL-1 alpha and TNF-alpha induced enhanced migration on fibronectin in one of the melanoma cell lines and were related to an upward shift in the alpha 4 and alpha 5 integrin subunit expression. Taken together, the findings indicate that expression of a particular receptor for IL-1 or TNF does not necessarily signal a motogenic response in melanoma cells, but induces heterogeneous shifts in beta 1 integrin expression. However, upregulation in alpha 4 and alpha 5 integrin subunits appears to relate to enhanced migration on fibronectin. PMID- 8006455 TI - Ultraviolet radiation--induced impairment of the early initiating and the late effector phases of contact hypersensitivity to picrylchloride: regulation by different mechanisms. AB - Two types of antigen-specific T cells are needed for the elicitation of contact hypersensitivity reactions. They act in an obligate sequence to mediate the early initiating and late effector phases of contact hypersensitivity, which are accompanied by skin-swelling responses at 2 and 24 h after challenge, respectively. The magnitude of the late ear swelling depends on that of the early swelling. We studied the influence of ultraviolet radiation on both phases of contact hypersensitivity to picrylchloride. Mice were exposed to subedemal doses of ultraviolet radiation on the shaved backs for four consecutive days. Four days later mice were sensitized on non-irradiated skin. Four days after sensitization mice were challenged on the ears, and swelling was measured 2, 4, and 24 h after challenge. The early and late phases of contact hypersensitivity were largely suppressed in ultraviolet-irradiated, actively sensitized mice. Transfer of immune lymphoid cells from donor mice that were sensitized 4 d earlier induced early and late components of contact hypersensitivity in naive recipients after challenge. Transfer of immune lymphoid cells from donors that were sensitized 1 d earlier only induced the early component of contact hypersensitivity. Ultraviolet irradiation of donor mice significantly reduced the capacity of the immune lymphoid cells to induce contact hypersensitivity. We show that lymphoid cells responsible for the early and late components of contact hypersensitivity are both affected. PMID- 8006454 TI - Cytokine induction in human epidermal keratinocytes exposed to contact irritants and its relation to chemical-induced inflammation in mouse skin. AB - In response to exogenous stimuli such as phorbol-12-myristate 13-acetate, ultraviolet B radiation, and lipopolysaccharide, human keratinocytes produce soluble mediators that are important in primary contact irritancy including cytokines that are associated with proinflammatory properties (interleukin-1 alpha [IL-1 alpha], tumor necrosis factor alpha), chemotaxis (IL-8), and growth activation (granulocyte/macrophage colony stimulating factor, IL-6, transforming growth factor alpha). We examined qualitative and quantitative changes in selected intracellular and secreted cytokines in human keratinocyte cultures in response to non-sensitizing contact irritants (croton oil, sodium lauryl sulfate, methyl salicylate, ethyl phenylpropiolate), sensitizing irritants (oxazolone, dinitrofluorobenzene), and ulcerative agents (phenol, benzalkonium chloride, chromium trioxide). The chemicals were also applied to mouse skin to assess whether the chemical-specific pattern of inflammation correlated with the in vitro production of keratinocyte-derived cytokines. Although all agents elicited neutrophils to the site of chemical application, time dependent and chemical specific patterns of inflammation could be detected. Sodium lauryl sulfate, phenol, and croton oil induced increases in IL-8 production at non-cytotoxic concentrations in semi-confluent human keratinocyte cultures. Phenol and croton oil stimulated tumor necrosis factor alpha production, whereas croton oil was the only agent found to induce granulocyte/macrophage colony-stimulating factor production. Croton oil, phenol, benzalkonium chloride, and dinitrofluorobenzene induced the intracellular production of IL-1 alpha without a concomitant release into the medium. The release of cytokines occurred in parallel with a relative increase in cytokine-specific mRNA transcripts. Studies using neutralizing antibodies to tumor necrosis factor alpha and IL-1 alpha demonstrated that IL-8 induction by croton oil and phenol occurred directly rather than through autocrine circuits. These data suggest that a given pattern of cytokine production is chemical-specific and may predict the contribution of keratinocytes to skin inflammation. PMID- 8006456 TI - Phenotypic and ultrastructural properties of antigen-presenting cells involved in contact sensitization of normal and UV-irradiated mice. AB - We investigated the surface phenotype and localization of hapten in antigen presenting cells involved in the induction of contact hypersensitivity or tolerance. Dendritic cells collected 18 h earlier from the draining lymph nodes of mice sensitized with fluorescein isothiocyanate (FITC), which induce contact hypersensitivity upon injection into the foot-pads of naive mice, stimulated proliferation of lymphocytes from FITC-specific T-cell lines. By immunoelectron microscopy, these cells expressed high amounts of surface Ia molecules but had a negligible amount of FITC on the cell membrane. The majority of the FITC was localized in discrete structures in the cytoplasm, including mitochondria, endocytic vesicles, lysosomes, and cored tubules. In contrast, lymph node cells conjugated with FITC in vitro did not stimulate proliferation of FITC-specific T cells and showed a heavy, uniform distribution of FITC throughout the cytoplasm. Draining lymph node cells from mice exposed to ultraviolet (UV) radiation and then sensitized by applying FITC to the UV-irradiated skin, which induce tolerance upon injection into naive mice, induced significantly less proliferation of FITC-specific T cells than draining lymph node cells from unirradiated mice. The differences in activity of these cells, relative to draining lymph node cells from unirradiated, FITC-sensitized mice could not be attributed to a decreased number of Ia+ dendritic cells in the DLN, decreased surface expression of Ia molecules on these cells, or an alteration in the intracellular localization of hapten. However, a significantly higher percentage of the FITC+ dendritic cells from UV-irradiated mice expressed mac-1, -2, and -3 and F4/80 macrophage markers than did those from unirradiated animals, and fewer cells contained Birbeck granules, suggesting that a different population of Ia+ antigen-presenting cells may reach the draining lymph nodes of UV-irradiated mice. PMID- 8006457 TI - Protective effect of N-acetylcysteine in hapten-induced irritant and contact hypersensitivity reactions. AB - The hapten-induced irritant and contact hypersensitivity reactions are experimental models of cutaneous inflammation in which tumor necrosis factor alpha is an important mediator. N-acetylcysteine is an anti-oxidant that inhibits the action of the nuclear factor-kB, which promotes the transcription of many genes, including the gene for tumor necrosis factor-alpha. We tested the ability of N-acetylcysteine to antagonize the development of the irritant and contact hypersensitivity reactions induced by the epicutaneous application of trinitrochlorobenzene in mice. Systemic and topical treatment with N acetylcysteine reduced skin swelling in both the irritant and contact hypersensitivity reactions; in the latter it also reduced the dermal leukocyte infiltrate. It also reduced the cutaneous expression of the mRNA for tumor necrosis factor-alpha in both conditions. These results show that N acetylcysteine antagonizes the development of irritant and contact hypersensitivity reactions and that its action includes a reduction in the expression of tumor necrosis factor-alpha mRNA. N-acetylcysteine may be useful in the treatment of cutaneous inflammation mediated by tumor necrosis factor-alpha. PMID- 8006458 TI - Cyclosporin A enhances cytokine and phorbol ester-induced fibroblast collagenase expression. AB - Cyclosporin A is successfully used in the treatment of scleroderma, a condition with excessive deposition of collagen in the dermis. Cultured human dermal fibroblasts were used as a model to study the effects of cyclosporin A on metalloproteinase expression and activity. Fibroblasts were treated with collagenase inducing agents, phorbol 12-myristate 13-acetate (PMA), cytokines interleukin-1 beta (IL-1 beta), tumor necrosis factor alpha (TNF alpha), and the calcium ionophore A23187 in the presence of cyclosporin A under serum-free conditions, and alterations in metalloproteinase expression were studied by Northern hybridization and immunoblotting analyses, and assays for collagenolytic activity. Induction of collagenase expression by PMA and cytokines was enhanced severalfold by 1-10 microM cyclosporin A. Treatment of cells with cyclosporin A alone caused only a minor increase in collagenase mRNA levels. The secretion of immunoreactive collagenase protein and the level of p-aminophenylmercuric acetate activatable collagenase activity were increased by PMA and further enhanced by cyclosporin A. The expression of the other metalloproteinases stromelysin-1, 92 kD gelatinase, and 72-kD gelatinase or metalloproteinase inhibitor TIMP-1 were not affected by cyclosporin A. Time dependence analysis of the expression of the mRNAs for c-jun and junB indicated that the induction of these genes persisted significantly longer in cells treated with both PMA and cyclosporin A than in cells treated with PMA alone. Enhanced induction of collagenase mRNA may thus result from prolonged AP-1 activity. The results indicate that cyclosporin A potently enhances the expression of collagenase in dermal fibroblasts. PMID- 8006459 TI - Expression of 72-kDa gelatinase (MMP-2), collagenase (MMP-1), and tissue metalloproteinase inhibitor (TIMP) in primary pig skin fibroblast cultures derived from radiation-induced skin fibrosis. AB - In addition to producing matrix degradation for normal tissue remodeling and repair, matrix metalloproteinases (MMPs) are also involved in various pathologic processes. MMPs and the tissue inhibitor of MMPs (TIMP) were investigated in primary cultures of pig fibroblasts from radiation-induced dermal fibrosis and compared to normal dermal fibroblasts. The free gelatinolytic, collagenolytic, and caseinolytic activities secreted into the culture medium were evaluated against specific 3H denatured collagen type I, native helical collagen, and casein alpha, respectively. The 72- and 68-kilodalton (kDa) forms of type IV collagenase were investigated by protease zymography and quantified by semi automated image analysis. Transcription of the interstitial collagenase (MMP-1) and TIMP genes was studied by Northern hybridization analysis. Results revealed that in fibrotic fibroblasts, the amount of MMP-1 mRNA was greatly reduced to undetectable levels whereas the amount of TIMP mRNA was increased fourfold compared to controls. Functional assays using specific 3H substrates demonstrated an overall decrease in free MMP activities. Concomitantly, catheptic collagenolytic activity decreased in fibrotic fibroblast extracts compared to controls. These results indicate that in addition to accumulating large amounts of collagen, proteoglycans, and fibronectin, pig fibroblasts from radiation induced dermal fibrosis also promote connective tissue matrix formation by repressing MMP-1 and stimulating TIMP expression at the transcriptional level, and by reducing overall free MMP and catheptic collagenolytic activities at the post-transcriptional level. In contrast, enzymography assays and automated image analysis demonstrated no significant change in the 72-kDa type IV collagenase activity of fibrotic pig skin fibroblasts. This opposite regulation of 72-kDa collagenase type IV to that of MMP-1 seems to indicate that it has a specific role in remodeling the extracellular matrix during wound healing, fibrogenesis, and angiogenesis. PMID- 8006460 TI - Expression of type II collagen at the middle stages of chick embryonic and human fetal skin development. AB - Using in situ hybridization techniques and RNase protection assays, type II collagen mRNA was transiently detected in the epidermis of chick embryonic skins during days 9-15 after fertilization, with a maximum expression at day 11. Immunohistochemical studies demonstrated that deposition of type II collagen was also transiently localized at the subepidermal region during days 10-15. Type II collagen gene and gene product concomitantly started to decline preferentially at the region where feather buds were being formed on day 12, and thereafter diminished at the region between feather buds. Using immunohistochemical methods, type II collagen was also detected in human fetal scalp skin at 17-23 fetal weeks at the subepidermal region, excluding the region beneath the hair follicles. These results indicate that the lack of type II collagen expression is related to the development of feather and hair at a certain stage of chick embryonic and human fetal skin development. PMID- 8006461 TI - Autoantibodies of neonatal lupus erythematosus. AB - The most common manifestations of neonatal lupus erythematosus (NLE) are cutaneous lupus and congenital heart block. Autoantibodies to Ro/SSA occur in almost all cases of NLE. The autoantibody response to Ro/SSA is complex, and antibodies may be detected to 60-kD Ro/SSA, 52-kD Ro/SSA, La/SSB, and U1 ribonuclear protein in anti-Ro/SSA-positive sera. Which of these anti-Ro/SSA related autoantibody specificities are important in the clinical expression of NLE is not conclusively established. We examined the autoantibody specificities in 20 maternal NLE sera to determine whether autoantibody specificities correlate with the clinical findings and to evaluate the relative importance of autoantibodies to the different Ro/SSA-associated proteins. Autoantibodies were examined using immunodiffusion, immunoblotting, and enzyme-linked immunosorbent assay. Eleven babies had NLE skin disease, 11 had heart block, and two had both skin disease and heart block. All 20 maternal sera had antibodies to 60-kD Ro/SSA. Eighteen of the 20 had antibodies to 52-kD Ro/SSA, nine had antibodies to La/SSB, and one had antibodies to U1 ribonuclear protein. The prevalence of anti La/SSB was the same in the skin-disease and heart-block subsets of NLE. Titers of anti-60-kD Ro/SSA were significantly (p < 0.02) lower in NLE skin disease maternal sera than in the NLE heart-block maternal sera. These results point out the importance of 60-kD Ro/SSA as a potential target in NLE. We speculate that the lower titers of anti-60-kD Ro/SSA in the sera from mothers of babies with skin disease may be due to substantial deposition of antibodies in the mothers' and babies' skin, leading to lower circulating titers, or may reflect a lower threshold for development of skin disease than for heart block. PMID- 8006462 TI - Patient measurement of psoriasis disease severity with a structured instrument. AB - The Psoriasis Area and Severity Index (PASI) is used by dermatologic investigators to assess psoriasis disease severity. PASI measures are time consuming and require trained personnel. We developed and evaluated a structured PASI-like instrument for self-measurement of psoriasis disease severity for use in future large-scale epidemiologic studies. The instrument consisted of a silhouette of a body for patients to shade in affected areas and of three modified visual analog scales for recording the redness, thickness, and scaliness of an average lesion. The resulting "patient PASI" score was compared to investigator PASI measurements in 43 patients with mild to severe psoriasis. Patients and investigator also recorded a subjective global severity score. The patient PASI score was highly predictive of the investigator PASI score (r2 = 0.71, p < 0.0001) and the investigator global score (r2 = 0.37, p < 0.0001). The patient global score was also predictive of the investigator PASI (r2 = 0.18, p < 0.0053) and the investigator global score (r2 = 0.10, p < 0.044), but these relationships exhibit wide predicted confidence intervals. Following the initial evaluation by 18.4 +/- 9.1 d of therapy, one-way t tests for paired samples (pre and post) showed significant improvements in the patient PASI (p < 0.003) and investigator PASI (p < 0.05). We conclude that although patients' overall scores may not allow for accurate prediction of clinical disease severity in a single individual, this structured instrument facilitates prediction of psoriasis disease severity in a population. PMID- 8006463 TI - Multiple cytochrome P450 isozymes in murine skin: induction of P450 1A, 2B, 2E, and 3A by dexamethasone. AB - Cytochrome P450s (P450s) are a supergene family of enzymes responsible for the metabolism of a wide range of endogenous and foreign compounds. P450 isozymes possess overlapping substrate specificity. Systemic administration of dexamethasone, a widely used topical agent in dermatologic practice, to animals is known to result in the induction of multiple P450 isozymes in liver. In this study the effect of topical application of dexamethasone to mice on P450 dependent monooxygenase activities, expression of P450 isozymes, and P450 mRNA levels in skin was assessed. The treatment of mice with dexamethasone resulted in significant induction of 7-ethoxyresorufin O-deethylase (2.3 times), 7 pentoxyresorufin O-depentylase (19.2 times), para-nitrophenol hydroxylase (7.5 times), and erythromycin N-demethylase (2.2 times) activities; the monooxygenases catalyzed preferentially by P450 isozymes 1A1, 2B1, 2E1, and 3A, respectively. Immunoblot analysis of cutaneous microsomes, employing antibodies directed against purified P450s 1A1/2, 2B1/2, 2E1, and 3A, showed that dexamethasone treatment results in an increased immunoreactivity (1.8-13.9 times). In immunohistochemical staining of skin with antibody against P4502B1/2, topical application of dexamethasone resulted in an increased reactivity towards microsomal protein in the suprabasal layer of the epidermis and with the cells of the hair follicles. Whereas constitutive expression of mRNAs for CYP1A1 and CYP2E1 was evident in murine skin, any change in the levels of these mRNAs following treatment with dexamethasone was not apparent. The results of our study indicate that the application of dexamethasone to murine skin results in the induction of several families of P450 isozymes, suggesting that murine skin contains multiple inducible P450 isozymes capable of participating in the metabolism of a wide range of xenobiotics and endogenous compounds. PMID- 8006465 TI - Human keratinocytes possess an sn-2 acylhydrolase that is biochemically similar to the U937-derived 85-kDa phospholipase A2. AB - The phospholipase A2 (PLA2) activities that are localized in the keratinocyte cytosolic and microsomal fractions were biochemically and pharmacologically characterized. The cytosol and to a lesser extent the microsome were sensitive to heat treatment and stable in the presence of sulfhydryl reducing agents. Both fractions were almost totally inactivated by reduction of pH to 2. The cytosolic activity demonstrated a sevenfold preference for arachidonic acid over oleic acid in the sn-2 position of substrate phospholipid and the microsome exhibited a fourfold preference. Neither the cytosol nor the microsome was inactivated by a neutralizing mouse monoclonal antibody 3F10 generated against recombinant human (rh) type II 14-kDa PLA2. Western immunoblot analysis of both fractions identified a high-molecular-mass protein in keratinocyte cytosol but not the microsome that migrated with rh 85-kDa PLA2. Neither the cytosol nor the microsome possessed immunoreactive bands that migrated with rh type II 14-kDa PLA2 when probed with monoclonal antibody 3F10. Further analysis of the cytosolic activity showed that it was activated by submicromolar concentrations of Ca2+, reduced by arachidonyl trifloromethylketone, a selective 85-kDa PLA2 inhibitor, but was unaffected by C-7 phosphonate phospholipid, a selective 14-kDa PLA2 transition state inhibitor. Taken together, the data supports the existence of a PLA2 activity in the cytosol that displays characteristics that are indistinguishable from those exhibited by the 85-kDa PLA2. Alternatively, both the cytosol and microsome were devoid of type II 14-kDa-like PLA2 activity. The failure of 12-epi scalaradial, a 14-kDa PLA2 inhibitor, to modify A23187 stimulated keratinocyte prostaglandin E2 release, was consistent with the biochemistry and suggests that the 85-kDa PLA2 may play an important role in keratinocyte prostaglandin E2 formation. PMID- 8006464 TI - A role for ions in barrier recovery after acute perturbation. AB - The epidermal cutaneous permeability barrier can be disrupted by treatment with topical solvents. Recent studies have shown that barrier recovery, measured by the recovery of transepidermal water loss towards normal, is inhibited by high extracellular Ca++ and K+, and accelerated by low extracellular concentrations of these ions. To examine the effects of Ca++ or K+ fluxes on barrier recovery, we tested the effects on transepidermal water loss recovery of agents that modify these fluxes. K+ channel agonists or blockers modified the inhibitory effects on barrier recovery induced by raised extracellular Ca++ and K+. In addition, Na+/K+ adenosine 5' triphosphatase inhibitors reversed the inhibitory effects of high extracellular Ca++ and K+. Our results suggest that barrier recovery requires both Ca++ and K+ fluxes and are consistent with the hypothesis that both verapamil or dihydropyridine-sensitive Ca++-permeable channels and Ca++-sensitive K+ channels participate in epidermal permeability barrier homeostasis. PMID- 8006466 TI - Carcinoma-associated 38-kD membrane glycoprotein MH 99/KS 1/4 is related to proliferation and age of transformed epithelial cell lines. AB - A 38-kD cell-surface glycoprotein (MH 99, KS 1/4) appears strongly elevated in epithelial malignancies, although it also occurs in a few immature, germ-cell phenotypic tissues in human epidermis. In this study, the expression and synthesis characteristics of the MH 99 antigen were examined in several transformed epithelial cell lines. Marked increase of MH 99 (by 100-200%) was found in highly proliferative cell populations, as demonstrated by radioimmunoprecipitation, fluorescence-activated cell sorter analysis, and proliferation experiments in cultures of spontaneously immortalized keratinocytes (HaCaT) squamous cell carcinoma lines (SCL 1 and SCL 2), and SV-40 transformed keratinocytes (130, 425, and HaSV). The relation of the MH 99 antigen to cell proliferation was underscored by a 70-75% decrease of synthesis in nonproliferating HaCaT cells treated with mitomycin C. Blocking of two distinct epitopes of the molecule with two different monoclonal antibodies (MH 99 and MM 104) decreased cell proliferation by approximately 25% (F = 519.6; df = 1,145; p < 0.0001), as compared to untreated cells and to cells treated with unrelated antibodies (BT 15 and J 143). Analysis of MH 99 synthesis in aging transformed keratinocytes cultured without passage revealed downregulation by approximately 50-60% after 60 d, indicating inverse correlation of the MH 99 antigen with increasing cell age. It seems, therefore, that the MH 99 antigen is directly correlated with cell proliferation and inversely correlated with increasing age of transformed epithelial cells, possibly playing an active role in the process of cell proliferation. PMID- 8006467 TI - Fluoride and dental health. PMID- 8006468 TI - Sugar and nutrient displacement. PMID- 8006469 TI - The Kilkenny health project 'a new perspective'. PMID- 8006470 TI - Nutrition advice and dental health objectives. PMID- 8006471 TI - Principles of enamel etching. AB - Amongst the innovations that have changed the practice of dentistry over the past three decades, the acid-etch technique and the use of composite resins may be regarded as two of the most influential. In 1955, Michael Buonocore, a researcher at the Eastmen Dental Centre in Rochester, New York, made the astute observation that the application of weak inorganic acid could alter the surface enamel so that bonding of a resin to the surface could take place. Buonocore experimented with acrylic resins but found these were much too weak to withstand the stresses exerted upon them in the mouth. It was not until Rafael Bowen developed a unique system containing 25 percent by weight of polymerisable monomer and 75 percent by weight of a vitreous filler--the composite resin--that the acid-etch technique became an effect procedure. This article reviews historical and current research, in the search to optimise the resin to enamel bond. PMID- 8006472 TI - Candidal infection as a complication of barrier membrane placement in a diabetic patient. AB - This report describes candidal infection as a complication of barrier membrane placement in a diabetic patient. This resulted in failure of the regenerative procedure and necessitated extraction of the tooth involved. Candidal hyphae were demonstrated within the dentinal tubules of the tooth. Subsequent to appropriate medical treatment to regain control of the diabetes there was an improvement in oral health. PMID- 8006473 TI - Updates in dental materials--Part 4. Ceramic materials. AB - Recent years have seen a number of innovations and developments with respect to dental materials and their applications in clinical dentistry. This series of short articles considers the more important aspects of these developments under the general term 'Updates in Dental Materials'. Dental composite systems and bonding to tooth material were discussed in Part I. Resin cements were treated in Part 2 and dental amalgams in Part 3. Part 4 deals with advances in ceramic materials. PMID- 8006474 TI - A study of patterns of chewing gum consumption amongst the Irish population. AB - A study to determine the pattern of chewing gum consumption amongst the Irish population was undertaken by means of a questionnaire completed by approximately 1,500 respondents from primary and secondary schools and third level colleges and employment exchanges. The results showed that approximately one-third of the respondents chewed gum at least once per day and a sizeable proportion of the younger population use sugar-free gum. PMID- 8006475 TI - Diet and early caries lesion. PMID- 8006476 TI - Sucrose and dental caries--considerations of the COMA panel. PMID- 8006477 TI - Sugar and obesity. PMID- 8006478 TI - Cariogenicity of eating patterns. PMID- 8006479 TI - Posttreatment stability in adult and adolescent orthodontic patients: a cast analysis. AB - Orthodontic treatment of adults differs in many ways from that of the conventional adolescent patient. Adults are essentially nongrowing and have lower turnover rates of alveolar bone. These and other factors may affect the posttreatment stability of adult dentitions. This study compared the stability of orthodontic outcomes in matched samples of adolescents (about 13 years of age) and adults (about 30 years old) at an average of 5 years out of treatment. Analysis disclosed few differences between age groups; both exhibited considerable stability. Regarding key treatment considerations--such as midline alignment, incisor overbite and overjet, incisor irregularity, and molar relationship--both groups changed to equivalent degrees (and very little on average). Although minor differences were found (eg, arch length decreased more in adults), treatment changes in this sample of adults were at least as stable as those in the adolescents for all clinically relevant variables. PMID- 8006480 TI - Health care reform and need for research. PMID- 8006481 TI - Incisor retraction and profile changes in adult patients. AB - The aims of this study were to evaluate the changes in the facial profile related to maxillary incisor retraction and to check for correlations between changes in the lip and changes in the positions of the teeth and alveolar bone during orthodontic treatment. Initial and final lateral cephalometric radiographs of 25 nongrowing Brazilian patients were selected for this study. All patients initially presented with Class I or II malocclusions and had their maxillary incisors retracted at least 2 mm during orthodontic treatment. Changes in lip position, length, and width, as well as changes in the positions of the alveolar bones and incisors, were calculated. Statistically significant differences from pretreatment to posttreatment were observed for all measurements except for upper lip length and point A. A high correlation was demonstrated between changes in the lower lip sulcus and point B and between changes in the lower lip sulcus and the mandibular incisor. Changes in the maxillary and mandibular incisors did not show a high correlation to the total lip changes, but high correlation coefficients were obtained when the changes in lip width were excluded from the total lip changes. In other words, changes in lip width tended to mask the changes in lip position caused by retraction of the maxillary incisors. PMID- 8006482 TI - Configurational differences in six skeletal landmarks in surgically treated and nonsurgically treated Class II patients. AB - Nongrowing patients with full-cusp Class II malocclusions can be treated with or without orthognathic surgery. The purposes of this retrospective study were to observe if skeletal factors influence treatment decisions and to investigate whether a discriminant analysis based on skeletal landmarks can be used to approximate the clinician's decisions. Information was obtained from the records of 44 postmenarchal women with a full-cusp Class II occlusion. Orthognathic surgery was suggested for 23 (52%) of the patients. They were on average 7 years older and presented with a greater maxillomandibular disharmony than the patients treated without surgery. Evaluation of the spatial relationships between the anatomic points by means of multidimensional scaling revealed that the shape of the triangle between articulare, supramentale (point B), and subspinale (point A) differed significantly between groups. For 33 of the 44 patients (75%), the clinician's decisions coincided with a linear discriminant function based on the spatial relationship of subspinale, supramentale, and articulare. These findings suggest that age as well as skeletal configuration played a role in the orthodontist's decision to use surgical or nonsurgical treatment. PMID- 8006483 TI - Validity and reliability of facial profile evaluation in vertical and horizontal dimensions from lateral cephalograms and lateral photographs. AB - Esthetic profile evaluation was performed by six judges on a random sample of 130 white women. Vertical and horizontal profile evaluations of the subjects' cephalograms were compared with vertical and horizontal profile evaluations of the same subjects' photographic slides. Statistically significant differences were found: Judges sometimes favored the photographic profile and sometimes favored the cephalographic profile. Esthetic treatment goals should be based on facial shortcomings as they are observed clinically or seen on a patient's photograph. PMID- 8006484 TI - Assessment of condylar position following bilateral sagittal split ramus osteotomy with wire fixation or rigid fixation. AB - In this study, 53 patients who underwent a bilateral sagittal split ramus osteotomy to advance the mandible were examined radiographically to assess condylar position presurgically, postsurgically, and posttreatment. Subjects were separated into two groups, 29 patients who received wire fixation and 24 who received rigid internal fixation. Condylar position changes were measured on tracings of submentovertex and transcranial radiographs at the time periods mentioned. Differences in condylar position were evaluated in two defined time intervals--T1, presurgical to postsurgical, and T2, postsurgical to posttreatment. Right and left sides were evaluated independently. No correlation between amount of advancement and condylar position change was identified within or between the fixation groups at T1 and T2. No correlation between change in mandibular plane angle and change in condylar position was identified within or between the groups at T1 and T2. Statistically significant differences were identified between the fixation groups in the degree of condylar change measured on the tracings of both submentovertex and transcranial radiographs both right and left sides, at time T1. There was also a significant difference in the change in mandibular plane angle at T1 between the fixation groups. It appears from this study that use of rigid internal fixation following bilateral sagittal split ramus osteotomy results in a statistically significantly greater condylar displacement than does wire fixation. Further research is required to determine whether these changes in condylar position are clinically significant. PMID- 8006485 TI - Adaptation and remodeling of the mandibular condyle following vertical ramus osteotomy in dogs. AB - This experiment investigated the effects of vertical ramus osteotomy (VRO) on normal mandibular condyles and those altered surgically to simulate trauma to the articular surface. Four dogs that received unilateral vertical ramus osteotomy to reposition the condyle downward and forward responded with progressive remodeling of the articular cartilage. A second group of four dogs that had grooves cut into the articular surfaces of both condyles showed more rapid healing on the side receiving VRO. In a third group (n = 4), vertical ramus osteotomy appeared to protect the articular cartilage from regressive remodeling after extraction of the molar teeth and prevent decreased vertical dimension of occlusion. The articular cartilage on the side with the vertical ramus osteotomy remained healthy, while the untreated side developed a narrower joint space and showed histologic evidence of thinning and degeneration of the fibrocartilage and increased density of the subchondral bone. PMID- 8006486 TI - Evaluation of masticatory function after sagittal split ramus osteotomy for patients with mandibular prognathism. AB - The aim of this study was to measure the changes in masticatory function for 1 year after sagittal split ramus osteotomy. Thirty prognathic patients who underwent preoperative and postoperative orthodontic treatment participated in this study. Their masticatory performance, occlusal contact area and points, and biting force were measured before surgery and 3, 6, and 12 months postoperatively. From 3 months after surgery, masticatory efficiency was greater than that found preoperatively, and the increase was significant 6 months after surgery. Occlusal contact area and points tended to increase from 3 months after surgery, and there was a significant increase 12 months after surgery. The bilateral biting force was lower 3 months after surgery than it was preoperatively, but it had increased significantly and was balanced on left and right sides 12 months after surgery. PMID- 8006487 TI - Recognition of herpes zoster ophthalmicus. AB - Herpes zoster ophthalmicus is a form of herpes zoster. Approximately 10 to 25 percent of zoster cases are ophthalmicus. The process is caused by reactivation of latent varicella virus affecting the fifth cranial nerve. Recognition of signs and symptoms leading to early diagnosis and treatment with acyclovir may alter the course and diminish damage to ocular structures. PMID- 8006488 TI - Endophthalmitis: an investigational process. AB - This was an investigational process of endophthalmitis in an operating room following cataract surgery. Studies have shown that patients' own skin flora is a prime consideration as a source of endophthalmitis. PMID- 8006489 TI - Drug abuse and the rapid eye test. AB - Drug effects contribute to impaired eye movements and visual information processing. Only a small percentage of clinical conditions can cause a positive rapid eye test, therefore, drug use must be suspected and should be confirmed by body fluid analysis. A drug may not reach the urine for one to two hours, while eye signs occur within fifteen minutes after sniffing, inhaling, or injecting the drug. The rapid eye test is inexpensive, nonintrusive, and detects the actual influence of the drug on the body. PMID- 8006490 TI - Cornea: confocal microscopy. AB - The confocal microscope opens a whole new window in early diagnosis of ocular conditions. Previously, details at the cellular level could only be viewed with conventional microscopes in a laboratory setting. By using confocal microscopy, results can now be obtained instantaneously in the living human eye. This non invasive high magnification technique provides real-time images of cornea morphology. PMID- 8006491 TI - Readership survey report. AB - All of the decisions made in the development of the journal were made by qualified and experienced people in ASORN, without benefit of knowing how perfectly the results would fit the readership. Since good judgment, experience, and knowledge have been and will continue to be the basis for making decisions, these results may be used to validate previous assumptions and decisions, and to reinforce those ideas currently being considered for improving the publication. PMID- 8006492 TI - A study investigating primary nursing, discharge teaching, and patient satisfaction of ambulatory cataract patients. AB - The purpose of this study was to investigate primary nursing, discharge teaching and patient satisfaction in a group of ambulatory cataract patients. A sample (n = 72) of subjects was divided randomly into a primary group (n = 36) and a control group (n = 36). Data on patient knowledge and satisfaction was collected by telephone 24-48 hours after surgery. Knowledge levels were high, and there was no significant difference between the primary and control groups in total score or in sub-scores on self-care, normal side effects, or complications. Women had significantly higher total scores than men (p > .05). There was a very high level of satisfaction with care, and almost all patients felt ready to go home when discharged. PMID- 8006493 TI - Stormy petrel. Polymorphic ventricular tachycardia. PMID- 8006494 TI - Diagnosis and management of hemoptysis. AB - Hemoptysis may present in patients both young and old, and its causes are numerous. The origin of the bleeding can be anywhere from the lips to the lung pleura, and a precise history and physical examination are essential in narrowing the search for the etiology. The chest film can effectively identify or exclude most lung neoplasms, but further evaluation is needed in those patients at high risk for cancer. The etiologies of hemoptysis are reviewed; emphasis is placed on a thorough history; the utility of diagnostic studies are explained; and efficient management is outlined. PMID- 8006495 TI - Noninvasive carcinoma of the breast: the rationale for various treatment options. AB - As a result of the increasing utilization of screening mammography, the incidence of noninvasive breast cancers has been steadily climbing. This phenomenon has inspired questions about the biological behavior and natural history of this disease and has sparked a controversy about which patients should be treated by local excision alone or local excision followed by breast irradiation and which patients require a mastectomy for disease-free survival. New data have been published within the past year shedding some light on these issues, but questions remain. PMID- 8006496 TI - Advanced stage at diagnosis: an explanation for higher than expected cancer death rates in Louisiana? AB - Data from the Louisiana Tumor Registry, Louisiana Vital Statistics Division, and the SEER program of the National Cancer Institute were explored to evaluate reasons for elevated cancer death rates in the absence of elevated cancer incidence in Louisiana. The results indicate that cancer patients in South Louisiana are more likely to be diagnosed with advanced stage disease than SEER patients. The Louisiana-SEER differences are greater for blacks than whites, and black patients are more likely to have advanced stage cancer than whites in Louisiana as well as in the SEER program. Of particular interest and concern is the finding that the increased risk of advanced stage disease in Louisiana is significant for cancers which can be detected early and, if so, effectively treated: colon, breast, and cervix. The findings reinforce the need for cancer control programs. PMID- 8006497 TI - Cancer incidence and mortality among African Americans. AB - In the future, the largest proportional increase in the population will be among minority groups. To date, there are a number of studies which document the disparities in cancer incidence and survival existing between white Americans and minorities, especially African Americans. African Americans have the highest cancer incidence and mortality rates in the United States. Much of this difference can be directly related to socioeconomic status. There are also cultural differences which result in differing attitudes towards health care. In the future, interventions designed to encourage cancer prevention and screening behaviors must seek to overcome the barriers to access in a culturally sensitive fashion. PMID- 8006498 TI - Women's health: early detection and screening practices for breast and cervical cancer. AB - A telephone survey of Orleans Parish residents (25 to 65 years old; annual family incomes < $40,000) was conducted to explore cancer-related knowledge, beliefs, and practices. This paper presents descriptive information about knowledge and practices pertinent to early detection of cancer (breast self-examination, Pap smear, and mammogram) among women (N = 315). Income-related differences were observed. Women in the lower income group were less likely to routinely practice breast self-examination, and also less likely to have had a recent Pap smear or mammogram. Gaps in knowledge regarding the purpose of Pap smears and mammograms were noted. This sample of women reported their physicians are not routinely recommending Pap smears or mammograms. Findings highlight the need for community education programs to enhance awareness of the purpose and importance of cancer screening practices, particularly among the poor. In addition, all medical professionals who have contact with women need to reiterate the importance of regular participation in cancer-screening practices. PMID- 8006499 TI - Cancer of the esophagus in Acadiana. AB - Cancer of the esophagus is a frequently fatal cancer whose incidence appears to be increasing. In Acadiana, esophageal cancer occurs predominantly in males, with a higher incidence in black males. Results of surgical treatment, with or without other therapy, are dismal. Combined treatment with chemotherapy and radiotherapy improved survival when compared to surgery. Survival benefits with chemotherapy and radiotherapy are, unfortunately, modest at present. PMID- 8006500 TI - Paradoxical poor prognosis of myeloma patients who demonstrate complete healing of bone lesions following treatment. AB - Multiple myeloma is the most common primary malignant bone neoplasm in adults, primarily over the age of 40. The most common radiographic findings include osteopenia, lytic lesions, and pathologic fractures. Although marked bone repair and healing can occur following therapy, this is often, paradoxically, a poor prognostic indicator. PMID- 8006502 TI - The role of genetic counseling in visually impaired adolescents. AB - The presence of genetic disorders in a high percentage of adolescents with significant visual impairments emphasizes the important role that genetic counseling can play in this population. However, its intended goals have been controversial. Responses to structured interviews about genetic counseling services from three groups of former students from the Kentucky School for the Blind were compared. One group consisted of students who had received genetic counseling; another, of students who had declined it; and a third, of students who had graduated before the service was available. In all groups, genetic counseling was viewed as a valuable service which would have been pursued by the majority of those who did not have the opportunity to receive it, and by many of those who refused it initially. Although genetic counseling did little to enhance knowledge of the cause of the specific visual impairment, it appeared to be useful in providing information regarding the risk of visual impairment in future offspring. A relatively high rate of unplanned pregnancies was noted in the group who had refused genetic counseling. The significance of this observation is uncertain. One interpretation is that the group refusing genetic counseling may have consisted of individuals who had fewer concerns as adolescents about family planning issues. These observations suggest that it may be appropriate to recommend to adolescents with significant visual impairments to defer childbearing until independent life experiences are accumulated outside the school setting. Then, prior to considering childbearing, genetic counseling should be sought. PMID- 8006501 TI - Gastrointestinal hemorrhage and small cell carcinoma. AB - Despite widespread dissemination of primary lung carcinoma by lymphangitic and hematogenous routes, acute gastrointestinal signs and symptoms are rarely presenting symptoms for bronchogenic carcinoma. We present a patient with small cell carcinoma of the lung who came to medical attention because of a lower gastrointestinal hemorrhage. In the absence of radiographically apparent pulmonary disease, the correct diagnosis was suggested by the biopsy specimens of the colon. PMID- 8006503 TI - A special educator's response to inclusion. PMID- 8006505 TI - The relevance of longitudinal research to learning disabilities. PMID- 8006504 TI - Dysrationalia descant. PMID- 8006507 TI - The social competence of students with learning disabilities over time: a within individual examination. PMID- 8006506 TI - Longitudinal studies of phonological processing and reading. PMID- 8006508 TI - Gender-biased language in learning disability textbooks. AB - The purpose of our study was to explore whether gender-biased language exists in two editions of popular learning disabilities (LD) textbooks by a female author and a male author. First, we examined whether gender-biased language (as measured by the frequency of gender-specific pronouns) was present in LD textbooks as a function of the author's gender and discovered that the male author exhibited approximately a 7:1 ratio in his use of masculine to feminine pronouns. In contrast, the female author demonstrated no significant difference in her use of gender-specific pronouns. Second, we investigated whether the degree of gender biased language has changed in different editions over the past 5 years and found a significant change only in the use of neutral pronouns by the male author. The existence of gender-biased special education textbooks raises the issue of the possible influence that such material may have on professional expectations concerning students with LD. In a field in which males are placed in LD programs in disproportionate numbers, the responsibilities of both authors and publishers are discussed, as their actions may have an impact on female students' rights in accessing appropriate educational services. PMID- 8006509 TI - Neuropsychological differences between college students with learning disabilities and those with mild head injury. AB - College students with learning disabilities (LD) and those with a history of mild head injury (MHI) are two groups whose learning problems are not adequately addressed. We administered a comprehensive battery of neuropsychological, psychological, and academic achievement tests to college students with learning problems (LD, n = 35; MHI, n = 25) and a control group (n = 22), and completed a series of discriminant function analyses. A combination of six neuropsychological and psychoeducational test variables produced statistically significant differences among the three groups. The instruments were sensitive to LD, MHI, and the differences between them. The students with LD performed poorly on linguistically oriented psychoeducational tests, whereas the students with MHI showed cognitive deficits in visual-spatial skills and in the areas of attention, memory, and novel problem solving. Differential interventions addressing these deficits appear to be indicated. PMID- 8006510 TI - The effects of educational placement and grade level on the self-perceptions of low achievers and students with learning disabilities. AB - Previous studies have yielded mixed findings as to the effect of learning disabilities (LD) on self-perception. We proposed that perceived competence in children who experience learning difficulties is affected both by age trends in self-appraisal processes and by the degree to which students' salient reference group is composed primarily of similar or more competent others. Measures of perceived competence (Harter, 1982) and perceived achievement were administered to 222 Israeli students (127 boys, 95 girls) in Grades 3, 5, and 7. The sample comprised 68 children with LD attending special schools, 68 children with LD attending special classes in regular schools, and 86 nonidentified low achievers in regular classes. As expected, perceived competence was similar and high in all groups at Grade 3, but was higher among the special school group than among the special class and low achieving groups at Grade 5. The benefits of special schools were less clear at Grade 7. Implications for research methodology and educational practice are discussed. PMID- 8006512 TI - High prevalence of familial defective apolipoprotein B-100 in Switzerland. AB - Familial defective apolipoprotein B-100 (FDB) is caused by a single G-to-A substitution at nucleotide 10,708 leading to an arginine to glutamine change at amino acid 3,500 of the apolipoprotein B-100 and thus, a reduced binding of the apolipoprotein B to the low density lipoprotein (LDL) receptor. In the present study, the prevalence of FDB in Switzerland was estimated, on the one hand, from a sample of 728 healthy volunteers whose origin was spread out over the entire German, French, and Romansh speaking parts of the country, and, on the other hand, from 142 unrelated Swiss families with primary hypercholesterolemia comprising 520 individuals. Using polymerase chain reaction (PCR)-based methods, three individuals were identified with the point mutation in the sample of volunteers, equivalent to a prevalence of approximately 1/240 (90% confidence interval: 1.51 x 10(-3)-1.03 x 10(-2)). The frequency of FDB in the sample of hypercholesterolemic subjects was 7/142, yielding a prevalence of approximately 1/190 extrapolated to the general population (90% confidence interval: 2.63 x 10( 3)-9.17 x 10(-2)). The combined prevalence based on both samples was 1/209. Thus, the investigated point mutation was highly prevalent in Switzerland and appeared to be more frequent than in other populations studied hitherto. Furthermore, the presence of the mutation was not necessarily associated with an elevation of serum cholesterol levels, particularly in young individuals. While in the non affected volunteers cholesterol levels increased between the age of 19 and 23 years by 0.22 mmol/l or by 5.6% (P = 0.001), this phenomenon was even more pronounced in individuals with FDB. The three volunteers with the point mutation demonstrated an increase in total cholesterol concentrations by 1.30 mmol/l or by 25% within 2 years, suggesting that, in the early twenties, cholesterol concentrations increase markedly from normal to elevated levels. Considering the estimated high prevalence and the relative ease of PCR-based tests, screening for FDB may become a standard procedure in patients with suggested familial forms of hypercholesterolemia. PMID- 8006511 TI - Lack of requirement for sterol carrier protein-2 in the intracellular trafficking of lysosomal cholesterol. AB - Previous work has established that the absence of peroxisomes, as occurs in Zellweger syndrome, is accompanied by the absence of cellular sterol carrier protein-2 (SCP2). In the present study, Zellweger-syndrome fibroblasts and peroxisome-deficient CHO-ZR78 cells were used to study the role of SCP2 in the intracellular transport of low density lipoprotein (LDL)-derived lysosomal cholesterol. By immunoblotting, peroxisome-deficient cells were confirmed to contain either no detectable SCP2 or far less SCP2 than corresponding normal cells. To monitor the transport of lysosomal cholesterol to the plasma membrane, we measured efflux of lysosomal cholesterol to HDL3 or phospholipid vesicles. SCP2-deficient cells, in comparison to normal cells, demonstrated little or no impairment in this efflux, suggesting that SCP2 is not required for the efficient delivery of lysosomal cholesterol to the plasma membrane. To examine the role of SCP2 in the delivery of lysosomal cholesterol to acyl-CoA:cholesterol acyltransferase (ACAT) in the rough endoplasmic reticulum (RER), the lysosomal and whole-cell cholesterol pools were differentially labeled, and then the ACAT mediated esterification of each pool was measured in response to an 8-h incubation with native LDL. For both cholesterol pools, esterification was stimulated by LDL, and the responses in normal and Zellweger cells were similar, demonstrating that SCP2 is required for neither the stimulation of ACAT that follows LDL uptake nor for the transport of lysosomal cholesterol to the RER. These findings suggest that some major aspects of lysosomal cholesterol trafficking in cells can occur by mechanisms not involving SCP2. PMID- 8006513 TI - Structural determination and packing analysis of a cholesteryl caprate/cholesteryl laurate solid solution. AB - This paper describes the X-ray crystal structure analysis of a cholesteryl ester solid solution, cholesteryl decanoate/cholesteryl laurate, grown from a bulk concentration with molar ratio 0.56/0.43. The unit cell is monoclinic with a = 12.969, b = 9.048, c = 31.137 A, and beta = 91.12 degrees and the space group P2(1) with Z = 4 (two molecules per asymmetric unit). The cell constants closely represent an average value of crystal parameters for the two pure components (hence, nearly corresponding to Vegard's law). Although the overall monolayer 1 lamellar packing is superficially similar to the earlier-studied cholesteryl undecanoate/cholesteryl laurate solid solution, a more partitioned distribution of acyl chains, i.e., a microfractionation corresponding to the observed nonideal phase behavior, is suggested. The behavior is similar to that found for n paraffin binaries cooled below a binodal phase boundary. Although it cannot be detected conclusively in this determination (due to high thermal motion of terminal acyl chain atoms), the non-stoichiometric combination of components also requires some partial occupancy of atomic sites on the chain termini. This structural arrangement is contrasted with the alternative expression found earlier for the more ideal undecanoate/laurate solid solution, i.e., random co packing leading to fractional atomic occupancy in an average laurate structure. The final weighted R factor for 4578 reflections is 0.138. PMID- 8006514 TI - Regulation of new fat cell formation in rats: the role of dietary fats. AB - Factors that stimulate formation of new adipocytes during development of obesity are yet to be identified. We examined whether diet acts directly on preadipocytes to stimulate replication and differentiation or indirectly by interacting with adipocytes to release or modify local growth factors. Male Sprague-Dawley rats were fed chow or diets high in starch (HST), saturated (HFS) or polyunsaturated (HFP) fats until 5-7 months of age. We found that, compared to other diets, HFS induced acceleration of replication of preadipocytes in primary culture (doubling time of retroperitoneal-derived preadipocytes: HFS 17 +/- 1 versus chow 32 +/- 6 and HFP 29 +/- 3 h, P < 0.05). HFS stimulated greater expansion of retroperitoneal fat than HFP even when caloric intake was equal and increased adipocyte number threefold. Preadipocyte pool size in inguinal and retroperitoneal fat pads changed relative to fat pad weight in rats fed all diets compared to chow, suggesting that the balance between the number of cells capable of replicating and those terminally differentiated was perturbed. Differentiation of preadipocytes and release of adipocyte growth factors in vitro were unaffected by diet. We concluded that dietary saturated fats induced expansion of adipose tissue mass more effectively than polyunsaturated fats and that this may, in part, be achieved by acceleration of preadipocyte replication. PMID- 8006515 TI - Nitrone spin trap lipophilicity as a determinant for inhibition of low density lipoprotein oxidation and activation of interleukin-1 beta release from human monocytes. AB - One means by which oxidation of low density lipoproteins (LDL) may contribute to atherogenesis is by their ability to induce the release of interleukin-1 beta from monocytes. In the present study, the effect of the lipophilic nitrone spin trap alpha-phenyl-tert-butylnitrone (PBN) on lipoprotein oxidation and subsequent release of interleukin-1 beta was examined. The hydrophilic nitrone spin trap alpha-(4-pyridyl 1-oxide)-N-tert butylnitrone (POBN) was also studied to evaluate the importance of spin trap localization within the lipoprotein. PBN inhibited copper-induced modification of low density lipoproteins in a dose-dependent fashion as judged by measurement of thiobarbituric acid reactive substances, electrophoretic mobility, and fluorescence changes, while POBN was relatively ineffective. As demonstrated by electron spin resonance spectrometry, spectra of PBN adducts were highly immobilized, which reflects their presence within the LDL matrix. Experiments using chromium oxalate, a paramagnetic relaxing agent, revealed that the PBN adduct is composed of a mobile component (exposed to the LDL aqueous phase) and an immobilized component, localized in the lipid-protein interface or in the bulk lipid. Cholesteryl ester phospholipid dispersions in which only the core cholesteryl esters are subject to oxidation were also used to compare PBN and POBN. Again, PBN prevented the oxidation of the core lipids while POBN had little effect, further suggesting that PBN is capable of localization within the core of LDL. In agreement, attenuation of low density lipoprotein oxidation by PBN also decreased their ability to induce interleukin-1 beta release from human monocytes. Conversely, POBN had little effect on the release of interleukin-1 beta from cells incubated with copper-oxidized lipoproteins. These results suggest that the ability of a nitrone spin trap to prevent low density lipoprotein oxidation and its biologic effect(s) requires its incorporation into the particle. PMID- 8006516 TI - Identification of (24E)-3 alpha,7 alpha-dihydroxy-5 beta-cholest-24-enoic acid and (24R,25S)-3 alpha,7 alpha,24-trihydroxy-5 beta-cholestanoic acid as intermediates in the conversion of 3 alpha,7 alpha-dihydroxy-5 beta-cholestanoic acid to chenodeoxycholic acid in rat liver homogenates. AB - Studies of chemical structure of the intermediates in the biosynthetic sequence between 3 alpha,7 alpha-dihydroxy-5 beta-cholestanoic acid (DHCA) and chenodeoxycholic acid have been undertaken. Radiolabeled DHCA was incubated with a rat liver preparation. The reaction products were converted to the p bromophenacyl esters, and analyzed by reversed-phase high performance liquid chromatography. Under the conditions used, the radioactivity was found in (24E)-3 alpha,7 alpha-dihydroxy-5 beta-cholest-24-enoic acid (31%) and (24R,25S)-3 alpha,7 alpha,24-trihydroxy-5 beta-cholestanoic acid (7%) along with the starting material (62%). Neither the 24Z isomer of the alpha,beta-unsaturated bile acid nor the other three isomers of the beta-hydroxy bile acid were detected. The findings support the proposed pathway for the side chain cleavage in chenodeoxycholic acid biosynthesis, which is thought to be identical to that of cholic acid biosynthesis. PMID- 8006517 TI - Phospholipid analogues: side chain- and polar head group-dependent effects on phosphatidylcholine biosynthesis. AB - In recent studies we showed that the phospholipid analogue hexadecylphosphocholine inhibits phosphatidylcholine biosynthesis by affecting the translocation of the rate-limiting enzyme of phosphatidylcholine biosynthesis, CTP:phosphocholine cytidylyltransferase (EC 2.7.7.15), to membranes, where it is active (Geilen et al. 1992. J. Biol. Chem. 267: 6719 6724). The present study was performed to investigate the structure-dependency of this effect. It is shown that the inhibitory properties of phospholipid analogues are dependent on their alkyl side chain length (dodecylphosphocholine < tetradecylphosphocholine < hexadecylphosphocholine < heptadecylphosphocholine < octadecylphosphocholine > eicosadecylphosphocholine). Furthermore, it is demonstrated that this inhibition of phosphatidylcholine biosynthesis by phospholipid analogues is also dependent on the polar head group (hexadecylphosphocholine >> hexadecylphosphoethanolamine = hexadecylphosphoserine). These effects result from an inhibition of the CTP:phosphocholine cytidylyltransferase and are not due to an inhibition of choline uptake or differences in the cellular uptake of the phospholipid analogues investigated. PMID- 8006518 TI - Metabolic mechanisms for responses to dietary cholesterol and fat in high and low LDL responding baboons (Papio sp.). AB - These studies were conducted to determine how plasma low density lipoprotein (LDL) cholesterol levels respond to dietary cholesterol, fed in increasing amounts with either corn oil or coconut oil diets, in high as compared to low LDL responding baboons; and to determine how apolipoprotein (apo) B transcription levels are modulated in response to dietary lipids. Eight high and eight low LDL responding pedigreed adult baboons, balanced for sire, age, sex, and weight, were challenged for successive 7-week periods with increasing levels of dietary cholesterol combined with either coconut oil or corn oil. At the end of each dietary period, plasma and lipoprotein lipids, apoB, apoA-I, and hepatic mRNA levels for apolipoproteins were measured. As dietary cholesterol increased, plasma cholesterol concentrations (mostly LDL cholesterol) increased in both phenotypes and with both types of fat, but phenotypic differences were greater with coconut oil. There was not a consistent dose-response relationship of plasma or LDL cholesterol levels to increasing intakes of dietary cholesterol. Neither dietary cholesterol, type of dietary fat, nor LDL phenotype affected hepatic apoB or apoE mRNA levels. In a second experiment to resolve the inconsistent dose response to dietary cholesterol, we fed the animals varying levels of dietary cholesterol combined with coconut oil, and separated the challenge periods with intervening 12-week chow periods. Plasma and LDL cholesterol and apoB concentrations rose consistently with increasing dietary cholesterol, and the slope of the increase diminished at the higher doses. The results suggest that genetic differences in the initial response of LDL cholesterol to dietary cholesterol and saturated fatty acids are not due to the differences in hepatic transcription of apoB, and that the preceding dietary intake of cholesterol and saturated fatty acids is a major determinant of the response of plasma lipids and the associated metabolic processes to a dietary challenge. The response of baboon plasma LDL cholesterol concentrations to dietary cholesterol, when fed with saturated fatty acids, is similar to that of humans. PMID- 8006519 TI - Regulation of the threshold for lipoprotein-induced acyl-CoA:cholesterol O acyltransferase stimulation in macrophages by cellular sphingomyelin content. AB - Macrophage acyl-CoA:cholesterol O-acyltransferase (ACAT), a key enzyme in atheroma foam cell formation, is stimulated by lipoproteins only after a "threshold" amount of cholesterol has accumulated in the cell. The present study explores the hypothesis that cellular sphingomyelin, by increasing the capacity of the cell to accommodate excess cholesterol, can influence the threshold of ACAT stimulation by lipoproteins. When the sphingomyelin content of macrophages was increased by either incubation with exogenous sphingomyelin or ceramide (a stimulator of endogenous sphingomyelin synthesis), the ability of acetyl-LDL to stimulate whole-cell ACAT activity was substantially reduced despite similar lipoprotein uptake and total cholesterol accumulation as in control cells. When the sphingomyelin content of macrophages was decreased by sphingomyelinase treatment, the ability of acetyl-LDL to stimulate whole-cell ACAT activity was enhanced despite no change in lipoprotein uptake. Importantly, microsomes isolated from control, sphingomyelin-, or sphingomyelinase-treated macrophages showed no difference in ACAT activity when assayed in vitro in the presence of exogenous cholesterol, suggesting that these treatments affected cholesterol trafficking. Lastly, a corollary of the hypothesis, that cells might adapt to a large increase in free cholesterol by increasing their sphingomyelin content, was supported by showing that the sphingomyelin content of macrophages increased 2.6 fold when the cells were induced to accumulate free cholesterol by incubation with acetyl-LDL plus an ACAT inhibitor. Thus, the sphingomyelin content of macrophages can influence the threshold at which ACAT is stimulated by lipoprotein delivery of cholesterol, and the cholesterol content of macrophages can influence the sphingomyelin content of the cell. These findings are consistent with a model in which cellular sphingomyelin plays an important role in accommodating pools of cellular cholesterol that result from the uptake of atherogenic lipoproteins by macrophages. PMID- 8006520 TI - Effects of increasing dietary palmitoleic acid compared with palmitic and oleic acids on plasma lipids of hypercholesterolemic men. AB - Palmitoleic acid is a minor monounsaturated fatty acid in the human diet and in blood plasma. Because macadamia oil is at least one potentially large source of palmitoleic acid, we tested its effect on plasma lipid levels against two other dietary fatty acids, oleic acid and palmitic acid. The dietary adjustments, through the use of supplements, provided comparisons of the three test fatty acids in which palmitoleic could be judged as behaving either like a saturated or a monounsaturated acid. Thirty-four hypercholesterolemic men ate the three test diets in random order in 3-week periods. Plasma total cholesterol and low density lipoprotein (LDL) cholesterol concentrations were similar with palmitic and palmitoleic acids and significantly higher than with oleic acid. High density lipoprotein (HDL) cholesterol was significantly lower with palmitoleic than with palmitic acid. The study confirms that, at least in hypercholesterolemic men, a modest increase in palmitic acid (+4% en) raises LDL cholesterol relative to oleic acid (+3% en), even when dietary cholesterol is low (< 165 mg/day). Palmitoleic acid (+4% en) behaves like a saturated and not a monounsaturated fatty acid in its effect on LDL cholesterol. PMID- 8006521 TI - A point mutation in the bile acid biosynthetic enzyme sterol 27-hydroxylase in a family with cerebrotendinous xanthomatosis. AB - Cerebrotendinous xanthomatosis (CTX) is a rare familial disorder characterized by progressive neurological dysfunction, atherosclerosis, and xanthomas with sterol storage in the nervous system, vessels, and tendons. Increased serum cholestanol, derived from intermediates of cholesterol catabolism, may possibly be a major cause of the disease. An examination was made of the cDNA encoding cytochrome P450 sterol 27-hydroxylase (CYP27) in hepatic mitochondria, considered a defective enzyme inducing CTX, in a Japanese housewife afflicted with CTX and her family. The proposita and one of her brothers, who also had CTX symptoms and hypercholestanolemia, were found to be homozygotic, carrying a point mutation in the CYP27 gene at Arg104 (CGG) to Trp104 (TGG). The mutant position has a 100% conserved positive charge in all known vertebrate cytochrome P450s and even in bacterial cytochrome P450cam. The mother of the proposita and another brother were both free of CTX symptoms and were heterozygotic for the mutation, although their plasma cholesterol increased moderately. An increase in plasma cholestanol alone would, thus, not appear to be a direct cause of sterol storage in CTX, while CTX is strongly suggested to be caused by defects in both alleles of the CYP27 gene. PMID- 8006522 TI - Biochemical and cytotoxic characteristics of an in vivo circulating oxidized low density lipoprotein (LDL-). AB - Using ion exchange high pressure liquid chromatography, total plasma low density lipoprotein (LDL) from 30 hypercholesterolemic and 10 normocholesterolemic cynomolgus monkeys was subfractionated into unmodified LDL (n-LDL) and more negatively charged LDL (LDL-). In hypercholesterolemic monkeys, the absolute LDL cholesterol level was 16.54 +/- 2.82 mg/dl (mean +/- SE) whereas in normocholesterolemic monkeys it was 2.39 +/- 0.12 mg/dl (P < 0.0001); the percentage of LDL- was 5.2 +/- 0.71% and 4.9 +/- 0.19% of the total LDL for hypercholesterolemic versus normocholesterolemic monkeys, respectively. LDL- averaged 5% and n-LDL 95% of the total plasma LDL cholesterol. To confirm and further elucidate the oxidative nature of LDL-, cholesterol and cholesterol oxide contents of LDL- and n-LDL were determined by capillary gas chromatography; 53.98 +/- 2.24% (mean +/- SE) of the LDL- cholesterol was oxidized whereas in n-LDL only 10.70 +/- 1.06% of the cholesterol was oxidized (P < 0.00001). The spectrum of oxysterols identified, which was similar for LDL- and n-LDL, suggested a free radical-mediated process for cholesterol oxidation. The principal oxysterols identified were: cholest-5-ene-3 beta, 7 alpha-diol, cholesta-3,5-diene-7-one, cholest-5-ene-3 beta, 7 beta-diol, 5,6 beta-epoxy-5 beta-cholestan-3 beta-ol, 5,6 alpha-epoxy-5 alpha-cholestan-3 beta-ol, 5 alpha-cholestan-3 beta,5,6 beta-triol, 3 beta-hydroxycholest-5-ene-7-one, and cholest-5-ene-3 beta,25-diol. To model one of the steps in the possible mechanism of atherogenesis, the cytotoxicity of LDL- was demonstrated to be greater against subconfluent than confluent aortic endothelial cells.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8006523 TI - In vivo 13C NMR analysis of acyl chain composition and organization of perirenal triacylglycerides in rats fed vegetable and fish oils. AB - Lipid composition of body fat can be a key indicator of nutritional status and a number of human disorders. In vivo 13C NMR provides for repeated, noninvasive analysis of fatty acyl chain composition on individuals, which circumvents classical problems of individual variation and repetitive invasive sampling. It also offers a unique opportunity to examine acyl chain organization in situ. This approach was used to examine the fatty acyl chain composition in the perirenal fat pads of rats fed olive, safflower, and menhaden oil-containing diets. These changes were then monitored during a diet switch between olive and menhaden oil fed rats. The fatty acid composition of perirenal fat pads and livers was also analyzed using gas chromatography for comparison with the in vivo NMR analysis. Both tissues assumed the general characteristics of diet fatty acyl chain and fatty acid composition and the diet switch induced a switchover of the perirenal composition in 30-45 days. These results indicate that a large portion of the diet fatty acyl chains were incorporated directly into adipose and liver tissues although some were also metabolized, particularly in menhaden oil-fed rats. Furthermore, changes in the in vivo spin-lattice relaxation times (T1) of fatty acyl carbons in the perirenal fat pads and their lipid extracts were followed and effective correlation times (tau eff) were calculated from the T1 data. The result indicated that the in vivo segmental mobility of acyl carbons was sensitive to changes in diet-derived fatty acyl chain composition and that the central region of the acyl chain was more sensitive to these changes. There was a qualitative similarity but quantitative differences in the tau eff of acyl carbons acquired in vivo and from extracts. These results suggest that adipose triacylglycerides experience an overall liquid-like microenvironment in vivo but with more restriction in their mobility, and that different factors may exist in governing their organization in situ versus in extracts. PMID- 8006524 TI - Biliary cholesterol secretion and bile acid formation in the hamster: the role of newly synthesized cholesterol. AB - In order to define the source of cholesterol for bile acid synthesis and biliary cholesterol, hamsters with an extracorporeal bile duct received an intraperitoneal bolus of [3H]water labeling newly synthesized cholesterol. Thereafter the enterohepatic circulation was interrupted and a nutrient solution was infused during the experimental period of 78 h. In a separate group, pravastatin was administered (54-78 h) to allow discrimination of 3H-labeled cholesterol recycling from plasma and newly synthesized hepatic cholesterol late during the experiment. In controls, newly synthesized biliary cholesterol and primary bile acids derived from cholesterol newly synthesized during the experiment amounted to 5% and 12% immediately after depletion of the bile acid pool (6-9 h), respectively. After longterm bile diversion these proportions increased to 56-63%, whereas 71% of plasma cholesterol was labeled. Pravastatin inhibited the secretion of biliary cholesterol, cholate, and chenodeoxycholate by 30, 50, and 44%, respectively. In contrast, the preinfusion tritium label was suppressed by a maximum of 16%, 14%, and 26%, respectively, reflecting the contribution of cholesterol newly synthesized in the hepatocyte as opposed to labeled cholesterol recycling from the plasma. It is concluded that in the hamster newly synthesized cholesterol is of minor importance as substrate for bile acid synthesis as well as biliary cholesterol, both under near physiologic conditions and after long-term bile diversion. Moreover, the hepatic cholesterol pools subserving the synthesis of the primary bile acids are identical but appear to be different from that of biliary cholesterol directly after the depletion of the enterohepatic bile acids. PMID- 8006525 TI - Mitochondrial metabolism of 12- and 15-hydroxyeicosatetraenoic acids. AB - We have previously demonstrated that peroxisomal-deficient human skin fibroblasts and mutant Chinese hamster ovary cells do not convert 12- and 15 hydroxyeicosatetraenoic acids (HETEs) to chain-shortened, polar metabolites, suggesting that peroxisomes are the intracellular location for beta-oxidation of these compounds. This implies that mitochondria do not beta-oxidize HETEs. To test this hypothesis we incubated highly purified rat liver mitochondria with [3H]12-(S)- and [3H]15-(S)-HETE in the presence of carnitine and an acylcoenzyme A-generating system. Extracts obtained from these incubations were analyzed for radiolabeled polar metabolites. Both HETEs were converted to apparent products of beta-oxidation, although the 12-HETE compound was a markedly better substrate. The presence of 50 microM 2-tetradecyloxirane carboxylate, a potent inhibitor of carnitine palmitoyl transferase, completely blocked 12- and 15-HETE conversion to these metabolites as did omission of carnitine from the medium. These data demonstrate carnitine-dependent beta-oxidation of HETEs in isolated mitochondria and suggest that mitochondria are competent to carry out this metabolic process in eukaryotic cells. Prevailing metabolic conditions in subcellular compartments may have precluded observation of mitochondrial activity in our earlier work with cultured cells. Alternatively, transport mechanisms may exist in the cell types studied that distribute 12-(S)- and 15-(S)-HETEs specifically to peroxisomes. PMID- 8006526 TI - Role of hepatic lipase in the uptake and processing of chylomicron remnants in rat liver. AB - The participation of hepatic lipase in the initial uptake and processing of chylomicron remnants was studied in the isolated, perfused rat liver. Hepatic lipase activity was either reduced by preperfusion of livers with heparin or inhibited with specific rat hepatic lipase antibodies. [3H]palmitate-labeled chylomicron remnants were recirculated through control and treated livers for 15 min; the livers were then flushed, homogenized, and endosome-rich fractions were isolated. Depletion of hepatic lipase activity by both methods reduced the uptake of chylomicron remnants and hydrolysis of their component triglycerides by perfused rat livers, but at the same time significantly increased the rate of endocytosis of those chylomicron remnants taken up. We conclude that hepatic lipase facilitates, but is not essential for, the initial uptake of chylomicron remnants by rat liver. Furthermore, endocytosis of chylomicron remnants does not require binding to hepatic lipase or the associated hydrolysis of remnant lipids. PMID- 8006527 TI - An efficient asymmetric synthesis of diacylglycerols. AB - A convenient preparation of 1,2-diacyl-sn-glycerol or 2,3-diacyl-sn-glycerol is described starting from allyl bromide. The latter was converted to allyl 4 methoxyphenyl ether, which is dihydroxylated using AD-mix as a catalyst to yield 3-O-(4'-methoxyphenyl)-sn-glycerol or 1-O-(4'-methoxyphenyl)-sn-glycerol in high yield and high optical purity. After diacylation, ceric ammonium nitrate was used to remove the 4-methoxyphenyl group under mild conditions that avoid acyl migration to 1,3-dipalmitoylglycerol. Thus chiral 1,2-diacylglycerol can be prepared from allyl bromide in just four steps in 78% overall yield and high enantiomeric excess. This scheme represents an inexpensive method for the large scale preparation of chiral 1,2-diacyl-sn-glycerol and 2,3-diacyl-sn-glycerol. PMID- 8006528 TI - Muscle testing response to provocative vertebral challenge and spinal manipulation: a randomized controlled trial of construct validity. AB - OBJECTIVE: To evaluate the relationship of muscle strength response to a provocative vertebral challenge and to spinal manipulation. DESIGN: Prospective double-blind randomized controlled trial: crossover and between subjects designs. SETTING: Laboratory: Center for Technique Research. PARTICIPANTS: Sixty-eight naive volunteers from the student body, staff and faculty of the college. INTERVENTIONS: Provocative vertebral challenge: standardized 4-5 kg force applied with a pressure algometer to the lateral aspects of the T3-12 spinous processes. INTERVENTION: manual high velocity low amplitude adjustment or switched-off activator sham. MAIN OUTCOME MEASURES: Piriformis muscle response was defined in two ways: reactivity (a decrease in muscle resistance, yes or nor, following a vertebral challenge); responsiveness (the cessation of reactivity following spinal manipulation). Relative response attributable to the maneuver (RRAM): the percent of an outcome attributable to the challenge or adjustment itself. RESULTS: Average RRAM = 16% reactivity to vertebral challenge; average RRAM = 0% responsiveness to spinal manipulation. Six to 10% of muscle tests were positive regardless of examiner, previous finding or intervention. CONCLUSIONS: For the population under investigation, muscle response appeared to be a random phenomenon unrelated to manipulable subluxation. In and of itself, muscle testing appears to be of questionable use for spinal screening and post-adjustive evaluation. Further research is indicated in more symptomatic populations, different regions of the spine, and using different indicator muscles. PMID- 8006529 TI - Sagittal plane rotation of the pelvis during lumbar posteroanterior loading. AB - OBJECTIVE: To determine the extent of sagittal plane rotation of the pelvis during lumbar spine posteroanterior loading. DESIGN: Quantitative study. SETTING: Biomechanics Laboratory, Faculty of Health Sciences, University of Sydney. PARTICIPANTS: Ten male and female subjects with no recent history of significant low back pain. INTERVENTION: A mechanical device was used to apply forces to the L3 spinous process. Data were collected during slow cyclical loading. MAIN OUTCOME MEASURE: The stiffness of the posteroanterior movement at the point of loading was measured, together with the sagittal plane rotation of the pelvis and the resistance to rotation provided by the bed on which the subject lay. RESULTS: Mean pelvic rotation was 2.1 degrees per 100 N applied force (SD 1.01 degrees/100 N). Mean posteroanterior stiffness was 13.4 N/mm (SD 3.13 N/mm) and resistance to pelvic rotation was 2.71 Nm/degree of pelvic rotation (SD 0.84 Nm/degree). CONCLUSION: During posteroanterior force application there is pelvic rotation of a magnitude that may be sufficient to have clinical significance. Abnormalities found during lumbar posteroanterior force application may originate in tissues caudad to the lumbar spine itself. PMID- 8006530 TI - The tension headache, migraine headache continuum: a hypothesis. AB - There is evidence in the literature that tension-type and migraine headaches do not exist as discrete pathophysiologic entities but form a continuum. The mechanisms for tension and migraine headaches are discussed and the evidence for this continuum, both basic scientific and clinical, is reviewed. A model for chronic headaches based on this evidence and based on clinical observations by the author is presented. Clinical and research implications of this model and means of testing the model are discussed. PMID- 8006532 TI - Electrical shock injury. AB - OBJECTIVE: To discuss the case of a patient who received an electrical shock injury to the back of his head and was co-managed by a neurologist and a chiropractor. The common manifestations of electrical shock injuries are presented. CLINICAL FEATURES: The patient was a 31-yr-old man. His initial symptoms consisted of headaches, dizziness, pain in the suboccipital area, tingling down both arms to the hands, nausea, blurred vision, increased sweating, chest pain, loss of appetite and memory lapses. The patient received a neurological examination, MRI of the brain, EEG, brain stem auditory evoked response and EKG. The neurologist's diagnosis was post-traumatic head syndrome following electrocution. INTERVENTION AND OUTCOME: He was treated by a neurologist and a chiropractor, with fair results. Chiropractic treatments were directed toward correcting the fixations, fibrotic tissue and joint proprioception in his neck using manipulation, physical therapy and active care exercises. CONCLUSION: Electrical shocks commonly cause immediate damage to the heart, nervous system and musculoskeletal system. They can also cause delayed complications days to years later, including cholelithiasis, cataracts and nervous system conditions such as ALS. Chiropractors can play an important role in managing the musculoskeletal manifestations of electrical shock injuries. PMID- 8006531 TI - A preliminary single case magnetic resonance imaging investigation into maxillary frontal-parietal manipulation and its short-term effect upon the intercranial structures of an adult human brain. AB - OBJECTIVE: To investigate the hypothesis that external cranial manipulation can cause change within the structures of the human brain. DESIGN: Single subject. SETTING: Private office. PARTICIPANT: A 42-yr-old man. INTERVENTION: MRI scan was administered without manipulative pressure but with the investigator's contacts on the test subjects maxillary palate and frontal/parietal region surrounding the bregma. OUTCOMES: Measurements were taken along the superior border of the corpus callosum, the width of the fornix column, the exposed anterior/superior wall of the lateral ventricle posterior to the fornix, the angular surface of the cerebellar central lobule and the posterior surface of the inferior colliculi. RESULTS: Results from the second MRI (administered during the application of external cranial pressure) demonstrated elimination of a 5-mm peak along the superior border of the corpus callosum and a 4-mm reduction in the width of the fornix column. The exposed anterior/superior wall of the lateral ventricle posterior to the fornix column increased 51 degrees cephalad with manipulative application. The angular surface of the central lobule altered by minus 26 degrees, and the posterior surface of the inferior colliculi varied by minus 7 degrees. The subject experienced no change in his asymptomatic condition as a result of this study. CONCLUSION: The present study supports the theory that external cranial manipulation affects the structure of the brain. It also suggests support for the theory regarding suture mobility. PMID- 8006533 TI - Chiropractic management and manipulative therapy for MRI documented cervical disk herniation. AB - OBJECTIVE: This case study reports on three cases of patients with documented cervical disk herniations, who responded to chiropractic management and manipulative therapy. CLINICAL FEATURES: Three patients complaining of neck pain with radiation of pain and tingling into the upper extremities had positive magnetic resonance imaging scans consistent with cervical disk herniations. They also had positive neurophysiologic testing with positive thermography scans and electrodiagnostic studies. INTERVENTION AND OUTCOME: The patients were prescribed a treatment regimen consisting of chiropractic management including bracing, physiotherapy, cervical manipulative procedures, traction and exercises. The patients responded well to care as evidence by posttreatment MRI, electrodiagnostic studies, clinical exam findings and thermography scan findings. CONCLUSION: Patients with and without nerve root compression secondary to cervical disk herniation can and do respond well to chiropractic care. Chiropractic management of this condition can and should be employed prior to more invasive treatment. PMID- 8006534 TI - Chiropractic education: reflecting the paradigm dilemma of chiropractic practice. PMID- 8006535 TI - Chiropractic scope of practice: another perspective. PMID- 8006536 TI - Chiropractic scope of practice. PMID- 8006537 TI - Chiropractic scope of practice. PMID- 8006538 TI - Chiropractic scope of practice. PMID- 8006539 TI - Chiropractic scope of practice. PMID- 8006540 TI - Chiropractic scope of practice. PMID- 8006542 TI - On health care ... at the brink of the abyss. PMID- 8006541 TI - Electrodiagnostic testing in back and extremity pain. PMID- 8006543 TI - Women in the health care system. Part I: As patients. PMID- 8006544 TI - Women in the health care system. Part II: As physicians. PMID- 8006545 TI - Cervical cancer screening and the role of the physician. PMID- 8006546 TI - Health care reform and the effect on families. PMID- 8006547 TI - Menopausal hormone replacement: not necessarily routine. PMID- 8006548 TI - Does abortion increase the risk of breast cancer? AB - According to this hypothesis, an early FFTP [first full-term pregnancy] would provide the greatest protection against breast cancer by drastically reducing, early on, the presence of undifferentiated and hence vulnerable breast cells, thereby decreasing the risk of subsequent transformation ... Other types of pregnancies, however, might increase the risk of breast cancer. If a woman's first pregnancy resulted in a first trimester abortion, the dramatic rise in undifferentiated cells that takes place during the first trimester would not be followed by the marked differentiation occurring during the second and third trimesters. The consequent sharp increase in the number of vulnerable cells would thus elevate breast cancer risk. PMID- 8006549 TI - Lessons from The Holocaust for American medicine. PMID- 8006550 TI - No exit. PMID- 8006551 TI - Controlling violence and other destructive impulses: a retail approach. PMID- 8006553 TI - Amoebic liver abscess in Thailand, clinical analysis of 418 cases. AB - From 1975 to 1983, 418 cases of amoebic liver abscess were admitted to the Department of Medicine, Siriraj Hospital without definite increase or decrease in the overall incidence and without seasonal preponderance. The age range was 16-81 yrs and mean age 42.4 yrs. Male to female ratio was 5:1. Pertinent clinical features were pain, fever and hepatomegaly with predominant involvement of the right lobe. Principal treatment consisted of needle aspiration combined with amoebicidal drugs, i.e. metronidazole, tinidazole and ornidazole. The efficacy of each was similar. Surgical drainage was required in only 2.1 per cent of uncomplicated cases and mortality rate was 0.7 per cent. Ruptures into pleural, pericardial and peritoneal cavity were found in 15.4 per cent and secondary infection in 11.9 per cent. Mortality rate of cases with complication was 7.14 per cent. Length of hospital stay was 12.8 days for the uncomplicated cases and 24.1 days for cases with complications (excluding the nonsurvivals). PMID- 8006552 TI - Clinical management of osteoporosis. PMID- 8006554 TI - Diabetes mellitus in the young in Srinagarind Hospital. AB - We studies 151 case of diabetes in the young (age at first visit < or = 35 yrs) from January 1982 to June 1990. We classified the 151 cases into non-insulin dependent diabetes mellitus (NIDDM) (38.4%), malnutrition-related diabetes mellitus (MRDM) (36.4%), insulin-dependent diabetes mellitus (IDDM) (9.9%), secondary diabetes mellitus (2.6%) and unclassified category (12.6%). MRDM can be further classified into 2 groups: 22.5 per cent were fibrocalculous pancreatic diabetes (FCPD) and 13.9 per cent were protein deficient pancreatic diabetes (PDPD). Abdominal roentgenography were performed in 103 cases (68.2%) and pancreatic calcification were found in 34/103 (33%). Farming occupation (p = 0.001), abdominal pain (p = 0.005), male sex (p = 0.0015) and cataracts (p = 0.02) were statistically more common in MRDM comparing to NIDDM and IDDM taken together. There were no statistically significant differences in history of alcohol consumption and raw cassava intake between both groups. Family history of diabetes mellitus were more common in NIDDM comparing to IDDM and MRDM. PMID- 8006555 TI - Drinking problem: a hidden problem in general practice. AB - A cross-sectional study of 320 general practice patients was undertaken to find the prevalence of problems drinkers and the ability of the SMAST and CAGE in detecting the problem. The problem drinkers were diagnosed by psychiatric interview in 7.5 per cent of all 320 patients. The reliability of the SMAST and CAGE was tested by a test-retest method and the repeatability indicies were substantial. The comcurrent validity of the SMAST and CAGE was tested by comparing them with the psychiatric diagnosis as a gold standard. The sensitivity and the specificity of the SMAST at the cut off > or = 3 which best discriminated subjects were 68 per cent and 77.8 per cent respectively. The CAGE had low sensitivity and specificity. PMID- 8006556 TI - Cytologic evaluation of smears obtained by self-collection vaginal tampon. AB - Papanicolaou (Pap) smear test is an established method of cervical cancer screening. However, most women in Thailand are still reluctant to undergo pelvic examination. A prospective study was carried out on the use of self inserted vaginal tampon to collect specimens for Pap test in 126 patients at Ramathibodi Hospital from September to October 1990. The tampons which were inserted overnight and removed by the patients themselves were smeared across a glass slide and immediately fixed in 95 per cent ethyl alcohol. Ninety-six point two per cent of the slides had adequate cells of good quality to be interpreted. The remaining 3.98 per cent could not be interpreted due to the lack of cells and poor cell fixation. It is concluded that the smears obtained by this method are satisfactory for cytologic evaluation. PMID- 8006557 TI - One layer continuous anastomosis of the alimentary tract with absorbable polydioxanone suture. AB - A prospective study using absorbable Polydioxanone (PDS) suture material in a one layer continuous technique for gastrointestinal anastomosis was conducted. There were 40 anastomoses constructed in 39 children and 61 anastomoses in 49 adults which were classified as "non-complicated anastomoses" without any clinical evidence of leakage or any other complications attributable to the anastomotic technique or to the suture materials. There were other 20 anastomoses created in 20 patients with malnutrition or those receiving chemotherapy and/or radiation or where there was tension at the anastomosis which were classified as "complicated anastomosis". Anastomotic leakage was observed in one patient (5%). The starvation period was 3.16 +/- 0.9 days compared to 3.46 +/- 1.0 days in the two layer technique "control" group. The rate of complications and the function of the GI tract in both non-complicated and complicated anastomoses after one layer continuous Polydioxanone anastomotic completion was not significantly different from those using conventional two layer anastomosis. The technique for one layer continuous suture is simple, easy and takes less time than the conventional method. This technique also theoretically provides better postoperative condition in which bowel anatomy and physiology can return to normal earlier, causing minimal tissue trauma, and less narrowing of the lumen although the evidence cannot be supported by this study. The Polydioxanone suture material is biodegraded by specific time, and hence allows normal growth of the anastomosed bowel; it is therefore suitable for both children and adults. PMID- 8006558 TI - Differential radiosensitization of radioresistant human cancer cells by caffeine. AB - The effect of caffeine, the methylated xanthine, in sensitizing the lethal action of ionizing radiation in vitro was investigated in human cancer cells which were clinically known to be radioincurable. The tumor lines were hepatocellular carcinoma and colon adenocarcinoma. Plateau phase cultures, after absorbing doses of 2 Gy, survived at a rate of 56.30 per cent for colon cancer and at 66.05 per cent for liver cancer. Both lines were radiosensitized by caffeine but at different potencies. Noteworthily, hepatocellular carcinoma whilst less radiosensitive than colon adenocarcinoma was 4 times more susceptible to caffeine. The lowest effective caffeine concentration for liver cancer was 2 mM which slightly exceeded the anticipated lethal concentration in humans. Research on radiosensitizing effect of methylated xanthines on hepatoma system still remains intriguing. Future work should be pursued with the use of less toxic compounds, such as theobromine. PMID- 8006560 TI - Pelagic paralysis from puffer fish poisoning. AB - A case of severe puffer fish poisoning was reported. After ingestion of puffer fish, symptoms develop rapidly with paralysis of the whole body, respiratory distress and nonreactive dilated pupils. After ventilatory support, the patient gradually recovered to normal activity within 48 hrs. PMID- 8006559 TI - Acarboxy prothrombin (PIVKA-II) in cord plasma in the south of Thailand. AB - Acarboxy prothrombin or PIVKA-II (protein induced by vitamin K absence or antagonist-II) was used to determine the presence of vitamin deficiency in newborn infants. Of 230 cord blood samples assayed by using ELISA method, 34.8 per cent were positive for PIVKA-II 0.13-17 AU/ml. The positive rate for PIVKA-II was greater in infants of primigravida (50.7%) than in those of multigravida (27.9%). All infants received prophylactic vitamin K, and no infant with positive PIVKA-II in cord blood subsequently had clinical bleeding. Because of the high prevalence of vitamin K deficiency in newborn infants in the South of Thailand, all newborn infants should receive prophylactic vitamin K at birth. PMID- 8006561 TI - Diabetic ketoacidosis in pregnancy. AB - Diabetic ketoacidosis, though uncommon, is a very serious complication in obstetrics. We reported 5 cases, which in retrospect could all have been prevented from occurring. Either a strong family of diabetes mellitus or presence of glycosuria were present in 4 cases. In 3 cases, the use of sympathomimetic and corticosteroid was the predisposing factor. Clinicians should have an index of suspicion in patients at risk and it might be prudent to screen for diabetes where the use of sympathomimetic and corticosteroid. PMID- 8006562 TI - Uterine rupture and labor induction with prostaglandins. AB - Uterine rupture in patients with labor induction with prostaglandin E2 application though uncommon is a very serious complication and preventable in obstetrics. We reported three cases of spontaneous uterine rupture following induction of labor with intracervical PGE2 gel administration in a dosage of 3-6 mg and two in whom labor was augmented with oxytocin infusion. To avoid such a complication, intracervical PGE2 gel administration should be started with a smaller dose and should augmentation with oxytocin be required careful evaluation and monitoring by a specialist is desirable. PMID- 8006563 TI - Cholesterol granuloma coincidence with a large and high jugular bulb: report of a case. AB - We present a case of right middle ear mass who had an abnormal large jugular foramen, high jugular bulb and large jugular vein on the same side. CT scan could not exclude a glomus tumor. Theoretically, retrograde jugular venography and carotid angiography will give the most useful information. However, in this case we tried to use the MRI scan instead. It showed high signal in T1W, T2W, GRT2W which correlated with blood pigments of methemoglobin in middle ear and mastoid. The low signal in MRI scan T1W, T2W clearly showed enlarged jugular vein, high jugular bulb with diverticulum which helped to excluding a glomus tumor. This finally turned out to be a cholesterol granuloma coincidence with abnormal enlarged jugular foramen and jugular vein. We suggest the MRI scan is very helpful and much safer for patients compared to angiography. PMID- 8006564 TI - Diagnostic radiographic findings and symptom-free teeth. AB - The determination of whether a symptom-free tooth has pulpal and periapical disease relies heavily on radiographic findings and pulp tests. A case of a symptom-free upper left first molar is presented. The radiographic evidence of pathological changes associated with the endo-antral syndrome coupled with diffuse pulpal calcifications facilitated the diagnosis of chronic pulpal periapical disease. Non-surgical root canal therapy resulted in periapical healing as shown on a follow-up radiograph. PMID- 8006565 TI - Effect of hydrogen peroxide and sodium perborate on the microhardness of human enamel and dentin. AB - The effect of 30% hydrogen peroxide and a paste of sodium perborate mixed with hydrogen peroxide at different temperatures and time intervals on the microhardness of human enamel and dentin was examined. Intact extracted human teeth were sectioned, embedded in acrylic resin, polished, and divided into four test groups related to surface treatment. The groups were 30% hydrogen peroxide at 37 degrees C, 30% hydrogen peroxide at 50 degrees C in an illuminated chamber, a paste of sodium perborate mixed with hydrogen peroxide at 37 degrees C, and a paste of sodium perborate mixed with hydrogen peroxide at 50 degrees C in an illuminated chamber. Teeth treated with distilled water at either 37 degrees C or 50 degrees C served as controls. The results indicated that treatment with 30% hydrogen peroxide reduced the microhardness of both enamel and dentin. This reduction was statistically significant after 5-min treatment for the dentin and after 15-min treatment for the enamel (p < 0.05). Treatment with sodium perborate mixed with hydrogen peroxide did not alter the microhardness of either the enamel or dentin at the tested temperatures and time intervals. It is therefore suggested that the use of high concentrations of hydrogen peroxide for bleaching purposes should be limited. Sodium perborate appears to be a less damaging bleaching agent. PMID- 8006566 TI - Apical sealing ability of Thermafil following immediate and delayed post space preparations. AB - Sixty extracted human teeth were prepared in a step-back flare method. Forty-five were obturated with plastic Thermafil and 15 were filled with lateral condensation. The Thermafil filled teeth were divided into three groups consisting of no post preparation, immediate post preparation, or delayed post preparation. Post preparations were not performed (controls) on the laterally condensed specimens. After 10 days of exposure to methylene blue dye, the specimens were decalcified in nitric acid for 72 h. A volumetric analysis measuring absorbance was then performed on each specimen. Within the testing parameters, no significant differences in leakage were observed among the tested groups. PMID- 8006567 TI - Indirect longitudinal cytotoxicity of root canal sealers on L929 cells and human periodontal ligament fibroblasts. AB - The cytotoxicity of two root canal sealers was evaluated in vitro. The powder components of both sealers, mainly zinc, were the same. The liquid for one sealer, Canals, was clove oil (included eugenol in more than 80%) and other materials. For the other, Canals-N, the liquid was composed of higher fatty acids and glycol. The experiments included two cell lines, heteroploid L929 mouse fibroblasts and diploid human periodontal ligament fibroblasts. Cytotoxicity was assessed using the radiochromium release method with 4-h exposure time. The assay involved using insert chambers in multiwell arrays to produce indirect contact of materials with the cell monolayer at a controlled distance of approximately 1 mm. This model also allowed for the longitudinal study of the same material sample to assess time-dependent changes in toxicity. Freshly mixed Canals was highly toxic (p < 0.01) to both cell lines. On and after 24 h of setting no toxicity was detected. At no time could cytotoxicity be observed when experimenting with Canals-N. These results indicate that both materials have a low content of water diffusible toxic components. Substituting eugenol can further decrease the toxicity of the sealer. PMID- 8006568 TI - In vitro attachment of Streptococcus sanguis to the dentin of the root canal. AB - The adhesion of a strain of Streptococcus sanguis (NCTC 7863) to the root canal dentin of bovine incisors was evaluated. Samples (104) were prepared and smear layer was created on the root canal surface with a tungsten carbide bur. The samples were divided into four groups, one of them serving as a control sample and the other three each receiving a different treatment: 6% citric acid for 2 min (group 3), 6% citric acid for 2 min + 6.25% sodium hypochlorite for 1 min (group 2), 6% citric acid for 10 min (group 4). After sterilization, they were incubated, and adhesion was assessed by direct examination using a scanning electron microscope. The use of irrigation solutions significantly reduced the adhesion in the latter two groups only, with a reduction of 15% (group 2) and 18.7% (group 4) in the number of bacteria. PMID- 8006569 TI - Relationship between clinical symptoms and enzyme-producing bacteria isolated from infected root canals. AB - The object of this study was to determine the correlation between clinical symptoms and the activity of enzymes such as collagenase, chondroitinase, and hyaluronidase produced by bacteria isolated from infected root canals. The materials examined consisted of 28 teeth with apical periodontitis from 25 patients. Bacteria producing collagenase or chondroitinase and hyaluronidase were found to be significantly related to subacute clinical symptoms involving percussion pain. The frequency of bacteria producing collagenase was higher in isolates from root canals with a radiolucent area over 5 mm in diameter than in those from canals having a radiolucent area less than 5 mm in diameter. PMID- 8006570 TI - Bacterial retention in canal walls in vitro: effect of smear layer. AB - When dentin is planed by endodontic instruments, a smear layer forms. Whether this layer should be removed is unknown and controversial. This study was conducted to assess the effect of the smear layer on retention of bacteria using an in vitro root canal bacterial colonization model. Canals of 26 extracted human canines were step-back prepared using 2.5% NaOCl. Teeth were then randomly divided into two groups based on the type of high volume final flush: 1-20 ml of sterile saline (0.85% wt/vol) or (2-10 ml of 17% EDTA followed by 10 ml of 2.5% NaOCl which removes smear layer. Streptococcus anginosus (milleri) was cultured in trypticase soy broth supplemented with 0.5% yeast extract at 37 degrees C in 5% CO2. Cells were harvested by centrifugation and resuspended in fresh media. Serial dilutions were performed to achieve inocula of 10(6) colony-forming units in a 30-microliters volume. Teeth were inoculated and incubated for 2 h in 5% CO2 at 37 degrees C. Following incubation, teeth were split and processed for microbiological analysis. Numbers of colonizing bacteria were determined by a spiral-plating system. Enumeration of the numbers of bacteria revealed a reproducible, order of magnitude difference (p = 0.0002) between teeth with smear layer (10(4) colony-forming units) versus teeth without smear layer (10(5) colony forming units). This suggests that smear layer produced during root canal therapy may inhibit bacterial colonization of root canals. One suggested mechanism is that smear layer may block bacterial entry into dentinal tubules. PMID- 8006571 TI - Effect of smear layer removal on the diffusion permeability of human roots. AB - Ten human maxillary incisors, extracted because of periodontal disease or nonrestorable caries, were obtained and instrumented to a size #70 K-Flex file at the working length using a standard stepback technique. Tritiated water (3H2O) was placed in the root canals and allowed to diffuse to the external surface of the roots until it reached a constant rate. The smear layer in each of the experimental roots was then removed using 0.5 M EDTA followed by 5.25% sodium hypochlorite (NaOCI). The constant rate diffusion of 3H2O was remeasured. The roots were then stored in deionized H2O for 2 months and the constant rate diffusion of 3H2O was remeasured. A statistically significant difference was noted between all three groups. A decrease in the diffusion permeability of the root to 3H2O was noted immediately after smear layer removal and the highest permeability was recorded after storage in the deionized water for 2 months. PMID- 8006572 TI - Presence of secretory IgA in human periapical lesions. AB - The concentration of secretory IgA in fluids present in the canals of 33 teeth was determined by the rocket immunoelectrophoresis technique. Except for the presence or absence of communication between the oral cavity and the root canals of the affected teeth, no other clinical finding showed significant statistical correlation with the presence of secretory IgA. The canals which were open to the oral flora had significantly higher concentrations of secretory IgA. Leaving canals open to the oral cavity may result in formation of periapical cysts. PMID- 8006573 TI - Retreatment efficacy 3 months after obturation using glass ionomer cement, zinc oxide-eugenol, and epoxy resin sealers. AB - The efficacy of ultrasonic retreatment, 3 months after obturation, in conjunction with Ketac-Endo, Roth's 801, and AH26 sealers was evaluated. Seventy-two root canals were prepared and obturated with gutta-percha and one of the sealers mentioned above. After 90 days, the canals were retreated by an ultrasonic technique and the retreatment time was recorded. The roots were split and the amount of debris that remained on the canal walls in three separate levels was scored. Compared by one-way and two-way analysis of variance, the mean scores of remaining debris at the different canal levels for the three sealer groups, as well as for each group, were not significantly different. The only significant difference was found in retreatment time for which Ketac-Endo was significantly slower to retreat than the other two sealers (p < 0.002). Thus, the results of this study showed that the amount of debris remaining on the root canal walls following retreatment 3 months after obturation is similar for Ketac-Endo, Roth's 801, and AH26 sealers, but the retreatment time for Ketac-Endo is significantly longer. PMID- 8006574 TI - Analysis of a referral-based endodontic practice: Part 1. Demographic data and reasons for referral. AB - There is little information in the dental literature regarding endodontic practice profiles and the reasons for referral to endodontic specialists. This study was undertaken to analyze various details of 2000 patients referred to an endodontist in Perth, Western Australia. The 2000 patients were comprised of 1295 (64.8%) females and 705 (35.2%) males. They were referred by 405 different dentists, clinics, or hospitals. The main reasons for referral were: management of pain (24.1% of patients), calcified/blocked canals (17.7%), endodontic retreatment (15.0%), trauma (12.9%), surgery (6.5%), and perforations (6.0%). Other reasons for referral included root resorption, fractured instruments, combined endodontic-periodontal lesions, second opinions, nervous patients, and medical complications. There were 312 people that did not require endodontic treatment, resulting in 1688 patients having treatment on 2221 teeth. Review appointments were attended by 50.2% of those patients due for recall examinations. The wide range of treatment procedures required and the high number of cases referred for diagnostic reasons indicate that endodontists must be highly skilled in all aspects of diagnosis, treatment planning, and treatment procedures. PMID- 8006575 TI - Warm vertical gutta-percha obturation: a technique update. AB - An updated version of the vertical warm gutta-percha obturation technique is presented. Recent research suggests that the physical properties of gutta-percha may be altered by using heat carriers that are too hot or by overheating gutta percha in a flame. The technique proposes a simple method of thermoplasticizing and delivering gutta-percha without overheating it. PMID- 8006576 TI - Cancer antigens: immune recognition of self and altered self. PMID- 8006577 TI - HLA class II transgenic mice: the chance to unravel the basis of HLA class II associations with disease. PMID- 8006578 TI - Oral administration of lipopolysaccharides activates B-1 cells in the peritoneal cavity and lamina propria of the gut and induces autoimmune symptoms in an autoantibody transgenic mouse. AB - About a half of the antierythrocyte autoantibody transgenic (autoAb Tg) mice, in which almost all B cells are detected in the spleen, lymph nodes, and Peyer's patches, but not in the peritoneal cavity, suffer from autoimmune hemolytic anemia. The occurrence of this disease is strongly linked to production of autoAb by activated peritoneal B-1 cells in the Tg mice. In this study, we have shown that oral administration of lipopolysaccharides (LPS) activated B-1 cells in the lamina propria of the gut as well as the peritoneal cavity in the healthy Tg mice and induced the autoimmune symptoms in all the Tg mice. The activation of peritoneal and lamina propria B-1 cells by enteric LPS is found not only in the anti-RBC autoAb Tg mice and normal mice but also in the aly mice which congenitally lack lymph nodes and Peyer's patches. These results suggest that B-1 cells in the two locations may form a common pool independent of Peyer's patches and lymph nodes, and can be activated by enteric thymus-independent antigens or polyclonal activators such as LPS. The induction of autoimmune hemolytic anemia in the Tg mice by enteric LPS through the activation of B-1 cells in the lamina propria of gut and in the peritoneal cavity suggests that B-1 cells and bacterial infection may play a pathogenic role in the onset of autoimmune diseases. PMID- 8006579 TI - Salmonella typhimurium initiates murine infection by penetrating and destroying the specialized epithelial M cells of the Peyer's patches. AB - Salmonella species are known to initiate infection of mammalian hosts by penetrating the intestinal epithelium of the small bowel. These bacteria preferentially interact with Peyer's patches which are collections of lymphoid follicles making up the gut-associated lymphoid tissue. We infected murine ligated intestinal loops with invasive and noninvasive Salmonella typhimurium strains for 30, 60, 120, and 180 min and examined the infected tissue by transmission electron microscopy. Within 30 min, we found that invasive S. typhimurium exclusively entered M cells found within the follicle-associated epithelium (FAE) of the Peyer's patches. Initially, interactions between invasive bacteria and enterocytes adjacent to the M cells were not found. Invasion of M cells was associated with the ability of the bacteria to invade tissue culture cells. S. typhimurium mutants, which were noninvasive for tissue culture cells, could not be found in ligated loops associated with M cells or enterocytes after incubations of 30, 60, 120, or 180 min. At 60 min, internalized invasive S. typhimurium were cytotoxic for the M cells. Destruction of an M cell formed a gap in the FAE which allowed organisms to invade enterocytes adjacent to the dead cell. Later in the infection process (120 and 180 min), the presence of bacteria beneath the FAE correlated with changes in the cytoarchitecture of the lymphoid follicle. In addition, replicating Salmonella began to enter both the apical and basolateral surfaces of enterocytes adjacent to infected M cells. PMID- 8006580 TI - Functional interaction between human histocompatibility leukocyte antigen (HLA) class II and mouse CD4 molecule in antigen recognition by T cells in HLA-DR and DQ transgenic mice. AB - Studies in vitro have suggested that a species barrier exists in functional interaction between human histocompatibility leukocyte antigen (HLA) class II and mouse CD4 molecules. However, whether mouse CD4+ T cells restricted by HLA class II molecules are generated in HLA class II transgenic mice and respond to peptide antigens across this barrier has remained unclear. In an analysis of T cell responses to synthetic peptides in mice transgenic for HLA-DR51 and -DQ6, we found that DR51 and DQ6 transgenic mice acquired significant T cell response to influenza hemagglutinin-derived peptide 307-319 (HA 307) and Streptococcus pyogenes M12 protein-derived peptide 347-397 (M6C2), respectively. Inhibition studies with several monoclonal antibodies showed that transgenic HLA class II molecules presented these peptides to mouse CD4+ T cells. Furthermore, T cell lines specific for HA 307 or M6C2 obtained from the transgenic mice could respond to the peptide in the context of relevant HLA class II molecules expressed on mouse L cell transfectants that lack the expression of mouse MHC class II. These findings indicate that interaction between HLA class II and mouse CD4 molecules is sufficient for provoking peptide-specific HLA class II-restricted T cell responses in HLA class II transgenic mice. PMID- 8006581 TI - Human major histocompatibility complex class II-restricted T cell responses in transgenic mice. AB - Transgenic mice expressing human major histocompatibility complex (MHC) class II molecules would provide a valuable model system for studying human immunology. However, attempts to obtain human class II-restricted T cell responses in such transgenic mice have had only limited success, possibly due to an inability of mouse CD4 to interact efficiently with human MHC class II molecules. To circumvent this problem, we constructed recombinant MHC class II genes in which the peptide-binding domain was derived from human DR sequences whereas the CD4 binding domain was derived from mouse I-E sequences. Purified chimeric human/mouse MHC class II molecules were capable of specifically binding DR restricted peptides. Human B cell transformants that expressed these chimeric MHC class II molecules could present peptide antigens to human T cell clones. Expression of these chimeric class II molecules in transgenic mice led to the intrathymic deletion of T cells expressing superantigen-reactive V beta gene segments, indicating that the chimeric class II molecules could influence the selection of the mouse T cell repertoire. These transgenic mice were fully capable of mounting human DR-restricted immune responses after challenge with peptide or whole protein antigens. Thus, the chimeric class II molecules can serve as functional antigen presentation molecules in vivo. In addition, transgenic mice expressing chimeric class II molecules could be used to generate antigen-specific mouse T cell hybridomas that were capable of interacting with human antigen-presenting cells. PMID- 8006582 TI - The V delta 1 T cell receptor repertoire in human small intestine and colon. AB - V delta 1 bearing T cells comprise the major population of gamma/delta T cells in the human intestinal tract. To gain insight into mechanisms involved in the generation of these cells and the diversity of their repertoire, we have characterized the junctional sequences of V delta 1 T cell receptor transcripts in the human small intestine and colon. Mucosal biopsies obtained from defined regions along the length of the small intestine or colon contained a high frequency of either one or a few identical in frame V delta 1 sequences. Less abundant sequences were also detected repeatedly throughout the length of small intestine or colon. Moreover, the intestinal V delta 1 repertoire in the small intestine and colon appeared compartmentalized and showed no overlap with the V delta 1 repertoire in peripheral blood. Dominant V delta 1 transcripts in each subject differed between the small intestine and colon, and the dominant transcripts within these sites differed among individuals. Analysis of small intestinal transcripts obtained at a 1-yr interval revealed that the V delta 1 repertoire was stable over time. The fact that the majority of V delta 1 transcripts, both dominant and rare, are distributed throughout a several meter length of the adult intestinal tract and are stable over time suggests they are not generated by an ongoing process of in situ VDJ gene rearrangement. Our results favor a model in which the repertoire of V delta 1 T cells in the intestinal tract is shaped by positive selection in response to a limited array of ligands before the migration of V delta 1 cells throughout the small intestine or colon. PMID- 8006583 TI - Characterization of a cis-acting regulatory element which silences expression of the class II-A beta gene in epithelium. AB - Class II major histocompatibility complex (MHC) genes encode for alpha/beta chain pairs that are constitutively expressed principally on mature B cells and dendritic cells in mice. These gene products are easily induced on macrophages with cytokines, and may also aberrantly appear on the surface of epithelium during immune injury. The appearance of class II determinants in parenchymal tissue potentially renders these somatic cells capable of antigen presentation to circulating CD4+ T lymphocytes, and their absence may be protective for normal tissues expressing self-antigens. The low surface class II expression observed on parenchymal cells generally correlates with low levels of mRNA, suggesting that transcription rate is a major element in class II regulation. To understand the transcriptional mechanism maintaining low basal surface expression of class II in somatic cells, we transiently transfected mini-gene reporter constructs to study the regulation of the murine A beta promoter in a cultured renal epithelial cell line. We describe here a negative cis-acting regulatory region located between 552 and -489 bp upstream of the A beta cap site that silences the transcriptional activity of the A beta promoter in epithelial cells in an orientation-dependent manner, and is also able to silence a heterologous promoter. This region is not active in class II-expressing B cells (BAL-17) in culture, but is functional in two other murine class II-negative cell lines, fibroblasts and thymoma T cells. Using competition electrophoretic mobility shift assays, we have localized the core protein binding site within this region to an 8-10-bp response element, designated A beta NRE, at -543 to -534 bp. A nuclear extract from BAL-17 cells does not bind to this element. Mutation of this site abrogates the transcriptional silencing activity of the region. We conclude that the transcription of class II-A beta in parenchymal cells, and some lymphocytes, can be actively repressed by an upstream silencing element. PMID- 8006584 TI - Interleukin 2 receptor gamma chain expression on resting and activated lymphoid cells. AB - The interleukin 2 receptor (IL-2R) is known to be comprised of at least three genetically distinct subunits termed alpha, beta, and gamma. These chains can be expressed individually or in various combinations resulting in distinct receptors with different affinities for IL-2. In contrast to alpha and beta, the cell surface expression of the gamma chain protein previously has not been well characterized. To examine cell surface expression of IL-2R gamma on hematopoietic cells, we developed two new monoclonal antibodies (mAbs) specific for this protein. Both 1A11 (immunoglobulin [IgG1]) and 3G11 (IgM) specifically reacted with murine cells transfected with IL-2R gamma cDNA, and immunoprecipitation studies indicated that both antibodies precipitated a protein of approximately 62 65 kD. Scatchard analysis of IL-2 binding to murine cells transfected with cDNA encoding combinations of IL-2R components demonstrated that neither beta nor gamma chain bind IL-2 with measurable affinity, but coexpression of both beta and gamma is sufficient to form an intermediate affinity receptor. In the absence of gamma chain, beta chain interacts with alpha chain to form a "pseudo-high" affinity receptor. In contrast, gamma chain does not appear capable of interacting with alpha in the absence of beta chain. Thus, gamma chain appears to interact only with beta, but beta chain is capable of interacting with both alpha and gamma. Using the newly developed mAbs to examine cell surface expression by immunofluorescence, resting T cells were found to express low levels of gamma chain without detectable alpha or beta. Early after mitogen stimulation, T cells expressed higher levels of alpha, beta, and gamma. However, at later time points, T cells expressed alpha and gamma in marked excess over beta. Thus, formation of high affinity IL-2R on activated T cells was primarily limited by beta chain expression. In contrast, resting natural killer (NK) cells constitutively expressed IL-2R beta without detectable alpha or gamma. After activation with either IL-2 or IL-12, expression of both alpha and gamma transiently increased and then returned to very low levels. Expression of functional IL-2R on resting and activated NK cells, therefore, appeared to be primarily limited by the expression of gamma chain. IL-2 binding studies with resting NK cells confirmed the results of immunofluorescence studies indicating the presence of very low numbers of intermediate affinity (beta gamma) receptors for IL-2 on these cells.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8006585 TI - Thymic selection of CD8+ single positive cells with a class II major histocompatibility complex-restricted receptor. AB - We describe mice that express a transgenic T cell receptor alpha/beta (TCR alpha/beta) specific for peptide 111-119 from influenza hemagglutinin presented by I-Ed class II major histocompatibility complex (MHC) molecules. The transgenic TCR is expressed on CD4+8- as well as CD4-8+ mature T cells even in mice that are deficient in rearrangement or do not express endogenous TCR-alpha genes. The CD4 8+ T cells require I-Ed class II MHC molecules for positive selection and can be activated to proliferate and to kill by I-Ed molecules presenting the relevant peptide. Full maturation of these cells, however, also requires the presence of class I MHC molecules. The results are compatible with the notion that T cell maturation requires multiple receptor-ligand interactions and establish an exception to the rule that class II-restricted TCRs are exclusively expressed by mature CD4+8- cells. PMID- 8006586 TI - Identification of a human cDNA encoding a functional high affinity lipoxin A4 receptor. AB - Lipoxin A4 (LXA4) triggers selective responses with human neutrophils that are pertussis toxin sensitive and binds to high affinity receptors (Kd = 0.5 +/- 0.3 nM) that are modulated by stable analogues of guanosine 5'-triphosphate (GTP). Here, we characterized [11,12-(3)]LXA4 specific binding with neutrophil granule and plasma membranes, which each display high affinity binding sites (Kd = 0.7 +/ 0.1 nM) that were regulated by GTP gamma S. Since functional LXA4 receptors are inducible in HL-60 cells, we tested orphan cDNAs encoding 7-transmembrane region receptors cloned from these cells for their ability to bind and signal with LXA4. Chinese hamster ovary (CHO) cells transfected with the orphan receptor cDNA (pINF114) displayed specific 3H-LXA4 high affinity binding (1.7 nM). When displacement of LXA4 binding with pINF114-transfected CHO cells was tested with other eicosanoids, including LXB4, leukotriene D4 (LTD4), LTB4, or prostaglandin E2, only LTD4 competed with LXA4, giving a Ki of 80 nM. In transfected CHO cells, LXA4 also stimulated GTPase activity and provoked the release of esterified arachidonate, which proved to be pertussis toxin sensitive. These results indicate that pINF114 cDNA encodes a 7-transmembrane region-containing protein that displays high affinity for 3H-LXA4 and transmits LXA4-induced signals. Together, they suggest that the encoded protein is a candidate for a LXA4 receptor in myeloid cells. PMID- 8006587 TI - Differential activation of transcription versus recombination of transgenic T cell receptor beta variable region gene segments in B and T lineage cells. AB - We have tested the ability of the T cell receptor beta (TCR-beta) transcriptional enhancer (E beta) to confer transcriptional activation and tissue-specific V(D)J recombination of TCR-beta V, D, and J segments in a transgenic minilocus recombination substrate. We find that the minimal E beta element, as previously shown for a DNA segment that contained the E mu element, promotes a high level of substrate D to J beta rearrangement in both B and T cells, but only promotes V beta to DJ beta rearrangement in T cells. Thus, both the E mu and E beta elements similarly direct V(D)J recombination of this substrate in vivo, supporting a general role for transcriptional enhancers in the normal regulation of this rearrangement process. Surprisingly, however, we found that both the V beta and DJ beta portion of the constructs were transcribed in an enhancer-dependent fashion (conferred by either E mu or E beta) in both B and T lineage cells, including normal precursor B cells propagated in culture. These findings indicate that, at least in some contexts, transcriptional activation, per se, is not sufficient to confer V(D)J recombinational accessibility to a substrate V gene segment. PMID- 8006588 TI - A novel ligand in lymphocyte-mediated cytotoxicity: expression of the beta subunit of H+ transporting ATP synthase on the surface of tumor cell lines. AB - Extracellular adenosine triphosphate (eATP) has been suggested to play a role in lymphocyte-induced tumor destruction. We now provide evidence that a protein responsible for ATP synthesis in mitochondria may also play a physiologic role in major histocompatibility complex-independent, lymphocyte-mediated cytotoxicity. A 51.5-kD protein (p51.5) bearing structural and immunologic characteristics of the beta subunit of H+ transporting ATP synthase (E.C. 3.6.1.34, beta-H+ATPase, published molecular mass of 51.6 kD) was detected on the plasma membrane of three different human tumor cell lines studied. NH2-terminal amino acid sequence analysis of purified p51.5 from K562 tumor cells revealed 100% homology of 16 residues identified in the first 21 positions to the known sequence of human mitochondrial beta-H+ ATPase. Antibody directed against a 21-mer peptide in the ATP binding region of beta-H+ ATPase (anti-beta) reacted with only one band on Western blots of whole tumor extracts and tumor membrane extracts suggesting that the antiserum reacts with a single species of protein. Anti-beta reacted with the cell membranes of tumor cells as determined by fluorescence-activated flow cytometry and immunoprecipitated a 51.5-kD protein from surface-labeled neoplastic cells (but not human erythrocytes and lymphocytes). Purified p51.5 bound to human lymphocytes and inhibited natural killer (NK) cell-mediated cytotoxicity. Furthermore, anti-beta treatment of the K562 and A549 tumor cell lines inhibited NK (by > 95%) and interleukin 2-activated killer (LAK) cell (by 75%) cytotoxicity, respectively. Soluble p51.5 upon binding to lymphocytes retained its reactivity to anti-beta suggesting that the ATP binding domain and the lymphocyte-receptor binding domain reside in distinct regions of the ligand. These results suggest that beta-H+ ATPase or a nearly identical molecule is an important ligand in the effector phase (rather than the recognition phase) of a cytolytic pathway used by naive NK and LAK cells. PMID- 8006589 TI - Structural and functional properties of region II-plus of the malaria circumsporozoite protein. AB - During feeding, infected mosquitos inject malaria sporozoites into the host circulation. Within minutes, the parasites are found in the liver where they initiate the first stage of malaria infection. All species of malaria sporozoites are uniformly covered by the circumsporozoite protein (CS), which contains a conserved COOH-terminal sequence called region II-plus. We have previously shown that region II-plus is the parasite's hepatocyte-binding ligand and that this ligand binds to heparan sulfate proteoglycans (HSPGs) on the hepatocyte membrane. Using a series of substituted region II-plus peptides, we show here that the downstream basic amino acids as well as the interdispersed hydrophobic residues are required for binding of CS to hepatocyte HSPGs. We also show that this positively charged stretch of amino acids must be aggregated in order to bind to the receptor. On the basis of this information, we have synthesized a multiple antigen peptide that mimics the hepatocyte-binding ligand. This construct inhibits both CS binding to HepG2 cells in vitro as well as CS clearance in mice. PMID- 8006590 TI - Purification, characterization, gene sequence, and significance of a bacterioferritin from Mycobacterium leprae. AB - The study of tissue-derived Mycobacterium leprae provides insights to the immunopathology of leprosy and helps identify broad molecular features necessary for mycobacterial parasitism. A major membrane protein (MMP-II) of in vivo derived M. leprae previously recognized (Hunter, S.W., B. Rivoire, V. Mehra, B.R. Bloom, and P.J. Brennan. 1990. J. Biol. Chem. 265:14065) was purified from extracts of the organism and partial amino acid sequence obtained. This information allowed recognition, within one of the cosmids that encompass the entire M. leprae genome, of a complete gene, bfr, encoding a protein of subunit size 18.2 kD. The amino acid sequence deduced from the major membrane protein II (MMP-II) gene revealed considerable homology to several bacterioferritins. Analysis of the native protein demonstrated the iron content, absorption spectrum, and large native molecular mass (380 kD) of several known bacterioferritins. The ferroxidase-center residues typical of ferritins were conserved in the M. leprae product. Oligonucleotides derived from the amino acid sequence of M. leprae bacterioferritin enabled amplification of much of the MMP II gene and the detection of homologous sequences in Mycobacterium paratuberculosis, Mycobacterium avium, Mycobacterium tuberculosis, Mycobacterium intracellulare, and Mycobacterium scrofulaceum. The role of this iron-rich protein in the virulence of M. leprae is discussed. PMID- 8006591 TI - Analysis of somatic mutation in five B cell subsets of human tonsil. AB - Using a series of phenotypic markers that include immunoglobulin (Ig)D, IgM, IgG, CD23, CD44, Bcl-2, CD38, CD10, CD77, and Ki67, human tonsillar B cells were separated into five fractions representing different stages of B cell differentiation that included sIgD+ (Bm1 and Bm2), germinal center (Bm3 and Bm4), and memory (Bm5) B cells. To establish whether the initiation of somatic mutation correlated with this phenotypic characterization, we performed polymerase chain reaction and subsequent sequence analysis of the Ig heavy chain variable region genes from each of the B cell subsets. We studied the genes from the smallest VH families (VH4, VH5, and VH6) in order to facilitate the mutational analysis. In agreement with previous reports, we found that the somatic mutation machinery is activated only after B cells reach the germinal center and become centroblasts (Bm3). Whereas 47 independently rearranged IgM transcripts from the Bm1 and Bm2 subsets were nearly germline encoded, 57 Bm3-, and Bm4-, and Bm5-derived IgM transcripts had accumulated an average of 5.7 point mutations within the VH gene segment. gamma transcripts corresponding to the same VH gene families were isolated from subsets Bm3, Bm4, and Bm5, and had accumulated an average of 9.5 somatic mutations. We conclude that the molecular events underlying the process of somatic mutation takes place during the transition from IgD+, CD23+ B cells (Bm2) to the IgD-, CD23-, germinal center centroblast (Bm3). Furthermore, the analysis of Ig variable region transcripts from the different subpopulations confirms that the pathway of B cell differentiation from virgin B cell throughout the germinal center up to the memory compartment can be traced with phenotypic markers. The availability of these subpopulations should permit the identification of the functional molecules relevant to each stage of B cell differentiation. PMID- 8006592 TI - Vascular permeability factor/endothelial growth factor (VPF/VEGF): accumulation and expression in human synovial fluids and rheumatoid synovial tissue. AB - Vascular permeability factor (VPF, also known as vascular endothelial growth factor or VEGF), is a potent microvascular permeability enhancing cytokine and a selective mitogen for endothelial cells. It has been implicated in tumor angiogenesis and ascites fluid accumulation. Since development of the destructive synovial pannus in rheumatoid arthritis (RA) is associated with changes in vascular permeability (synovial fluid accumulation), synovial cell hyperplasia, and angiogenesis, we examined synovial fluids (SFs) and joint tissue for the expression and local accumulation of VPF/VEGF. VPF/VEGF was detected in all of 21 synovial fluids examined and when measured by an immunofluorimetric assay, ranged from 6.9 to 180.5 pM. These levels are biologically significant, since < 1 pM VPF/VEGF can elicit responses from its target cells, endothelial cells. Levels of VPF/VEGF were highest in rheumatoid arthritis fluids (n = 10), with a mean value (+/- SEM) of 59.1 +/- 18.0 pM, vs. 21.4 +/- 2.3 pM for 11 SFs from patients with other forms of arthritis (p = 0.042). In situ hybridization studies that were performed on joint tissues from patients with active RA revealed that synovial lining macrophages strongly expressed VPF/VEGF mRNA, and that microvascular endothelial cells of nearby blood vessels strongly expressed mRNA for the VPF/VEGF receptors, flt-1 and KDR. Immunohistochemistry performed on inflamed rheumatoid synovial tissue revealed that the VPF/VEGF peptide was localized to macrophages within inflamed synovium, as well as to microvascular endothelium, its putative target in the tissue. Together, these findings indicate that VPF/VEGF may have an important role in the pathogenesis of RA. PMID- 8006593 TI - A new gene coding for a differentiation antigen recognized by autologous cytolytic T lymphocytes on HLA-A2 melanomas. AB - It has been reported previously that antitumor cytolytic T lymphocyte (CTL) clones can be isolated from blood lymphocytes of HLA-A2 melanoma patients, after stimulation in vitro with autologous tumor cells, and that some of these CTL clones lyse most HLA-A2 melanomas. A first antigen recognized by such CTL clones was previously shown to be encoded by the tyrosinase gene. We report here the identification of another gene that also directs the expression of an antigen recognized on most melanomas by CTL clones that are restricted by HLA-A2. The gene, designated Melan-A, is unrelated to any known gene. It is 18 kb long and comprises five exons. Like the tyrosinase gene, it is expressed in most melanoma tumor samples and, among normal cells, only in melanocytes. PMID- 8006594 TI - Opposing regulatory effects of thioredoxin and eosinophil cytotoxicity-enhancing factor on the development of human immunodeficiency virus 1. AB - Exogenous recombinant human thioredoxin (rTRX, > or = 500 nM), a dithiol reductase enzyme, inhibited the expression of human immunodeficiency virus (HIV) 1BaL in human macrophages (M phi) by 71% (range, 26-100%), as evaluated by p24 antigen production and the integration of provirus at 14 d after infection. The stoichiometric reducing agent N-acetylcysteine (NAC) also inhibited HIV production, but to a lesser degree, and only at 30,000-fold higher concentrations. Exogenous rTRX is cleaved by M phi to generate the inflammatory cytokine, eosinophil cytotoxicity-enhancing factor (ECEF). In contrast to rTRX, rECEF (concentrations from 50 pM to 2 microM) enhanced the production of HIV by 67% (range, 33-92%). Thus, whereas TRX is a potent inhibitor of the expression of HIV in human M phi, cleavage of TRX to ECEF creates a mediator with the opposite effect. TRX also inhibited the expression of integrated provirus in the chronically infected OM 10.1 cell line, showing that it can act at a step subsequent to viral infection and integration. PMID- 8006595 TI - Human astrocytes inhibit Cryptococcus neoformans growth by a nitric oxide mediated mechanism. AB - Cryptococcus neoformans is an opportunistic fungus that causes life-threatening meningoencephalitis in 5-10% of patients with acquired immune deficiency syndrome. Cryptococcal meningoencephalitis is characterized by a lymphohistiocytic infiltrate, accumulation of encapsulated forms of C. neoformans, and varying degrees of glial reaction. Little is known about the contribution of endogenous central nervous system cells to the pathogenesis of cryptococcal infections. In this study, we investigated the role of astrocytes as potential effector cells against C. neoformans. Primary cultures of human fetal astrocytes, activated with interleukin 1 beta plus interferon gamma inhibited the growth of C. neoformans. The inhibition of C. neoformans growth was paralleled by production of nitrite, and reversed by the inhibitors of nitric oxide (NO.) synthase, NG-methyl-mono-arginine and NG-nitro-arginine methyl ester. The results suggest a novel function for human astrocytes in host defence and provide a precedent for the use of NO. as an antimicrobial effector molecule by human cells. PMID- 8006596 TI - Class I dependence of the development of CD4+ CD8- NK1.1+ thymocytes. AB - A small subset of functionally active CD4+ CD8- thymocytes express the NK1.1 marker, as do most CD4-CD8- NK1.1+ thymocytes. Previous studies have failed to implicate a role for major histocompatibility complex (MHC) or related molecules in the selection of the CD4+ CD8- NK1.1+ subset. We report here that the development of most of these cells is sharply reduced in class I-deficient mice, but not in class II-deficient mice. Hence, some CD4+ T cells are class I dependent and not class II dependent. Unlike conventional T cells, however, the development of NK1.1+ thymocytes in both the CD4+ CD8- and CD4- CD8- subsets is dependent on class I MHC expression by hematopoietic cells and not thymic epithelial cells. We propose that these populations are selected by nonpolymorphic class Ib or CD1 molecules. PMID- 8006597 TI - The role of Raf-1 in the regulation of extracellular signal-regulated kinase 2 by the T cell antigen receptor. AB - Triggering of the T cell antigen receptor (TCR) complex activates the serine/threonine kinase Raf-1 whose function is necessary for TCR induction of the interleukin 2 gene. Raf-1 has been identified as a candidate mitogen activated protein (MAP) kinase kinase kinase (MKKK) and thus has the potential to couple the TCR to the activation of the MAP kinases such as ERK2. In the present study, the role of Raf-1 in ERK2 regulation of ERK2 in T cells has been explored. A constitutively active Raf-1 kinase, v-raf, or a dominant inhibitory Raf-1 mutant were expressed transiently from the pEF BOS vector in Jurkat cells and the effects of these Raf-1 mutants on a coexpressed ERK2 reporter was assessed. The action of the constitutively active Raf-1 was to stimulate the ERK2 kinase, whereas the dominant negative version of Raf-1 inhibited the ERK2 activation induced by triggering of the TCR. These data indicate a role for Raf-1 in the regulation of ERK2 in T cells. PMID- 8006598 TI - Calnexin retains unassembled major histocompatibility complex class I free heavy chains in the endoplasmic reticulum. AB - The assembly of major histocompatibility complex (MHC) class I molecules involves the association of heavy (H) chain with beta 2-microglobulin (beta 2m) and peptide. Unassembled class I H chains do not exit the endoplasmic reticulum (ER) and this is exemplified by the beta 2m-deficient human melanoma FO-1 where free class I H chains are unable to complete assembly. In pulse chase experiments involving FO-1 cells, unassembled free class I H chains were shown to be stably associated with calnexin (IP90/p88), a 90-kD integral membrane molecular chaperone of the ER. To establish a role for calnexin in mediating this retention, we transfected FO-1 cells with a cytoplasmic tail deletion mutant of calnexin. Since the cytoplasmic tail contains the ER retention motif, these mutant calnexin molecules leave the ER and progress to the cell surface. In these stable transfectants of FO-1, free class I H chains also exited the ER and trafficked to the cell surface with calnexin, thus establishing a role for calnexin in the quality control of MHC class I assembly through mediating the ER retention of incompletely assembled class I H chains. PMID- 8006599 TI - Anti-immunoglobulin E treatment decreases worm burden and egg production in Schistosoma mansoni-infected normal and interferon gamma knockout mice. AB - The immunoglobulin E (IgE) response is generally considered an essential component of the host defense against parasitic helminths such as Schistosoma mansoni. In contrast, work on antischistosome vaccines suggests that interferon gamma (IFN-gamma) is the critical immune mediator for vaccine-induced immunity to the parasite. In this study, the total IgE response to a primary S. mansoni infection was suppressed by anti-IgE treatment in both normal mice and in mice with defective IFN genes (gene knockout [GKO]). Reduction of the IgE response resulted in decreased worm burden and a decrease in the number of eggs produced per worm in both normal and GKO mice. Whereas anti-IgE treatment also resulted in reduced hepatosplenomegaly, granulomas around existing schistosome eggs showed normal cellularity. Serum interleukin 4 levels fell in response to the reduction in serum IgE as well. The data suggest that IgE plays a detrimental, rather than beneficial, role for the host in schistosomiasis. Furthermore, the absence of IFN gamma was found to be of little consequence to the host-response to adults or eggs in a primary schistosome infection. PMID- 8006600 TI - B cell diversification and differentiation in the periphery. PMID- 8006601 TI - Mouse bone marrow-derived mast cells (mBMMC) obtained in vitro from mice that are mast cell-deficient in vivo express the same panel of granule proteases as mBMMC and serosal mast cells from their normal littermates. AB - The ear, skin, and purified serosal mast cells of WBB6F1/J-(+/+) (WB-(+/+)) and WCB6F1/J-(+/+) (WC-(+/+)) mice contain high steady-state levels of the transcripts that encode mouse mast cell protease (mMCP) 2, mMCP-4, mMCP-5, mMCP 6, and mouse mast cell carboxypeptidase A (mMC-CPA). In contrast, no mast cell protease transcripts are present in abundance in the ear and skin of WBB6F1/J W/Wv (W/Wv) and WCB6F1/J-Sl/Sld (Sl/Sld) mice which are mast cell-deficient in vivo due to defects in their c-kit and c-kit ligand genes, respectively. We now report that the immature bone marrow-derived mast cells (mBMMC) obtained in vitro with recombinant interleukin 3 (rIL-3) or WEHI-3 cell conditioned medium from WB (+/+), WC-(+/+), W/Wv, and Sl/Sld mice all contain high steady-state levels of the mMCP-2, mMCP-4, mMCP-5, mMCP-6, and mMC-CPA transcripts. As assessed immunohistochemically, mMCP-2 protein and mMCP-5 protein are also present in the granules of mBMMC from WB-(+/+), WC-(+/+), and W/Wv mice. That Sl/Sld and W/Wv mBMMC contain high steady-state levels of five granule protease transcripts expressed by the mature serosal, ear, and skin mast cells of their normal +/+ littermates suggests that c-kit-mediated signal transduction is not essential for inducing transcription of these protease genes. Because rIL-4 inhibits the rIL-10 induced expression of mMCP-1 and mMCP-2 in BALB/cJ mBMMC, the ability of rIL-4 to influence protease mRNA levels in WC-(+/+) mBMMC and W/Wv mBMMC was investigated. Although rIL-10 induced expression of the mMCP-1 transcript in WC-(+/+) and W/Wv mBMMC, rIL-4 was not able to suppress the steady-state levels of the mMCP-1 transcript or any other protease transcript in these cultured mast cells. Thus, not only do BALB/cJ mBMMC express fewer granule proteases than mBMMC from mast cell-deficient strains and their normal littermates but the subsequent induction of late-expressed proteases in BALB/cJ mBMMC is more tightly regulated by IL-3 and IL-4. PMID- 8006602 TI - M cells--entryways of opportunity for enteropathogens. PMID- 8006604 TI - The marking of removable dentures both full and partial dentures. PMID- 8006605 TI - A discussion of "Postmortem alcohol production in fatal aircraft accidents," (J. Forensic Sci., Vol. 38, No. 4, July 1993) PMID- 8006603 TI - Proliferating dendritic cell progenitors in human blood. AB - CD34+ cells in human cord blood and marrow are known to give rise to dendritic cells (DC), as well as to other myeloid lineages. CD34+ cells are rare in adult blood, however, making it difficult to use CD34+ cells to ascertain if DC progenitors are present in the circulation and if blood can be a starting point to obtain large numbers of these immunostimulatory antigen-presenting cells for clinical studies. A systematic search for DC progenitors was therefore carried out in several contexts. In each case, we looked initially for the distinctive proliferating aggregates that were described previously in mice. In cord blood, it was only necessary to deplete erythroid progenitors, and add granulocyte/macrophage colony-stimulating factor (GM-CSF) together with tumor necrosis factor (TNF), to observe many aggregates and the production of typical DC progeny. In adult blood from patients receiving CSFs after chemotherapy for malignancy, GM-CSF and TNF likewise generated characteristic DCs from HLA-DR negative precursors. However, in adult blood from healthy donors, the above approaches only generated small DC aggregates which then seemed to become monocytes. When interleukin 4 was used to suppress monocyte development (Jansen, J. H., G.-J. H. M. Wientjens, W. E. Fibbe, R. Willemze, and H. C. Kluin-Nelemans. 1989. J. Exp. Med. 170:577.), the addition of GM-CSF led to the formation of large proliferating DC aggregates and within 5-7 d, many nonproliferating progeny, about 3-8 million cells per 40 ml of blood. The progeny had a characteristic morphology and surface composition (e.g., abundant HLA-DR and accessory molecules for cell-mediated immunity) and were potent stimulators of quiescent T cells. Therefore, large numbers of DCs can be mobilized by specific cytokines from progenitors in the blood stream. These relatively large numbers of DC progeny should facilitate future studies of their Fc epsilon RI and CD4 receptors, and their use in stimulating T cell-mediated resistance to viruses and tumors. PMID- 8006606 TI - A discussion of "A computer program for the estimation of time of death" (J. Forensic Sci., Vol. 38, No. 4, July 1993) PMID- 8006607 TI - Further commentary on "Police and their sidearms" (J. Forensic Sci., Vol. 38, No. 1, 1993, pp. 11-12; Vol. 38, No. 5, 1993) PMID- 8006608 TI - Terminal ballistics of the 9mm with Action Safety bullet or Blitz-Action-Trauma (BAT) ammunition. AB - Specialty ammunition creating atypical gunshot wounds of entrance can create confusion and may be misinterpreted by pathologists unfamiliar with the terminal ballistics of these projectiles. The previously unreported wound ballistics caused by the 9mm with Action Safety bullet described in a homicide highlights the atypical entrance wound(s) and wounding capacity of this novel ammunition. Manufactured by Geco division of Dynamit Nobel, the bullet consists of a nonjacketed solid copper alloy bullet body without a conventional lead core. The large deformation well and part of the smaller central channel is filled with a hard plastic core and post that creates a round nose bullet. The internal ballistics and unique design allow the plastic nose cap and post to separate from the copper alloy base while still in the barrel. The radiolucent nose cap leaves the bullet's path but can still penetrate tissue giving the appearance of a separate but smaller entrance wound. The sharp leading edge of the deformation well and relative high velocity of the bullet body creates a punched out entrance wound with minimal marginal abrasion. When the plastic nose cap or fragments of the plastic post impact the subject, test firings may allow an inference to the muzzle-target distance even in the absence of soot deposition or stippling. PMID- 8006609 TI - A retrospective and prospective study of cerebral tissue pulmonary embolism in severe head trauma. AB - In an attempt to determine the incidence of pulmonary embolization of cerebral tissue as the result of severe head trauma with and without dural penetration, we have collected the autopsy reports at our institution of all head injury victims over the past 3.5 years. The retrospective and prospective histologic examination of these cases revealed a total of 10% to have emboli of cerebral tissue within the pulmonary vasculature. Immunohistochemical staining of the emboli confirmed the neural origin of the tissue. The dura mater proved to be intact in 70% of the cases of cerebral embolization. We feel this provides evidence that embolization of cerebral tissue may occur without rupture of the dura and/or large venous sinuses. This observation is of clinical as well as forensic importance, as cerebral tissue emboli are a rich source of thromboplastin in the systemic and pulmonary vasculature and may contribute to the morbidity and mortality of head injuries. PMID- 8006610 TI - Death investigation report forms (DIRFs): generic forms for investigators (IDIRFs) and certifiers (CDIRFs). AB - On the basis of data collection procedures and forms used in various death investigation offices, we developed generic death investigation report forms (DIRFs). One form was designed for documenting information collected by the initial investigator of death, and another form was designed for documenting information collected by the medical examiner, pathologist, or other person who certifies the death or otherwise finalizes the investigation by determining the cause, manner, and circumstances of death. The benefits, problems, and criteria associated with designing the forms are discussed. Both the investigators DIRF (IDIRF) and the certifier's DIRF (CDIRF) are available in printed or electronic form for those who wish to use them or to modify them according to their specific needs. We hope that these DIRFs will be useful and promote uniformity in documenting death investigations. PMID- 8006611 TI - Standard language in death investigation laws. AB - Death investigation statutes and practices vary among the 50 states. We reviewed the Model Postmortem Examinations Act, recommendations of the National Association of Medical Examiners, the College of American Pathologists' "criteria for autopsies," and the death investigation statutes and practices in each state. By consolidating the terminology from these various information sources, we developed a list of death categories for which investigation by medical examiners or coroners in the United States is either mandated, commonly performed, or recommended. The list contains specific categories of death, which fall under these three more general areas: 1) unexpected and unexplained deaths, 2) deaths from intentional and unintentional external causes, and 3) deaths that fall under specialized categories related to the decedent's age, environment, or medical conditions, or to the method of bodily disposition. To promote greater uniformity in the death investigation practices among states, we recommend that the Model Postmortem Examinations Act be modified to explicitly recommend certain types of deaths for investigation and that states modify their death investigation statues to conform to such provisions. Presently, in states where death investigation statutes lack specificity in detailing the types of deaths that should be reported for possible medico-legal investigation, our recommendations, if not in conflict with local statutes, might be used as practice guidelines for the reporting and investigation of certain types of deaths. PMID- 8006612 TI - Investigation of the 1987 Indianapolis Airport Ramada Inn incident. AB - On October 20, 1987, a military reserve aircraft lost power during a transcontinental flight and attempted an emergency landing at The Indianapolis International Airport. The pilot ejected and the disabled and pilotless aircraft struck a bank building. It then skidded across the street and entered the lobby of The Airport Ramada Inn where it exploded. This incident was unusual in that the fatal injuries occurred in individuals on the ground and not in the occupant of the aircraft. Seven people were killed in the lobby area and two were trapped in a laundry where they died of smoke inhalation. A tenth person died of burns ten days later. Minor injuries were reported among four hotel guests, two firefighters and the Air Force pilot. A multiagency mass disaster-plan had been formulated and rehearsed in preparation for the Panamerican Games, which had been held in Indianapolis in August 1987. A number of volunteers arrived before a security perimeter was established. They began an undocumented removal of the bodies from the scene and were about to remove valuables for "safekeeping" when stopped by coroners' office personnel. Fatalities resulted from smoke inhalation, burns or a combination. Bodies were identified by a combination of dental records, personal effects and visual means within 24 hours. The problems encountered in managing this disaster scene will also be compared with previously reported incidents. PMID- 8006614 TI - Violent suicide in South Yorkshire, England. AB - Differences in the characteristics of those individuals choosing violent methods of suicide in South Yorkshire were studied. With the exception of jumping from a height, these methods were more frequently used by males, with a particular male predominance in deaths due to self-immolation, railway collision, hanging, firearms, and electrocution. The most potentially painful/disfiguring methods of suicide, jumping from a height, self-immolation, and railway deaths, were favored by the young. Drowning, stabbing and cutting and electrocution were common among the elderly. Severe mental illness was common amongst those choosing some of the most painful or disfiguring modes of death (jumping from a height; self immolation; cutting/stabbing and road traffic "accidents") particularly when compared to the principal alternative of hanging. The same group of causes of death was associated with a high proportion of individuals who had previously attempted suicide. Severe mental illness was not so obviously a feature of the railway or firearm deaths. Hanging represented more than half the cases included in the study and showed a sex ratio of over 4 to 1 in favor of males. However, all seven individuals of non-European origin, six of whom were female, chose to hang themselves. Whereas half of the females aged under 40 jumped from a height, hanging was the method of choice in the age group 40 to 59. Among males, hanging was particularly favored by those with what might be considered an impulsive reason for suicide, namely, the end of a relationship with a member of the opposite sex. A high proportion of these were intoxicated with alcohol and a high proportion left a suicide note. PMID- 8006615 TI - A decade of train-pedestrian fatalities: the Charleston experience. AB - Although the cause of death is rarely in doubt in train-pedestrian fatalities, the manner of death is often unclear. The distinction between accident and suicide can only be made after careful evaluation of the history, scene investigation, autopsy findings, and toxicologic data. A retrospective analysis of 25 consecutive train-pedestrian fatalities investigated by our office between 1982 and 1992 is reported. The victims were predominantly healthy, young males. All but one person died at the scene. The cause of death was massive blunt trauma in 88% of the cases. In one case, the sole injury was decapitation. A tissue or blood ethanol level greater than 99 mg/dL was detected in 80% of the cases. A total of 60% of the cases involved persons likely to have been sitting or lying across the railroad tracks; all but one of these victims were intoxicated. The manner of death was determined to be accidental in 92% of our cases. Decapitation by a moving train is an injury highly suggestive of suicide. Massive blunt trauma, especially in the setting of ethanol intoxication, was highly associated with accidental death. Toxicologic analysis is essential in discriminating willful suicide from alcohol-induced incapacitation resulting in accidental death. Homicide, disguised as an accident or suicide, must be ruled out in all cases. Accurate determination of the manner of death is an important issue regarding civil litigation and dispersal of insurance benefits. PMID- 8006613 TI - Fatal injuries caused by guns using shotshell: case reports and ballistic studies. AB - The authors present six cases of homicide and suicide in which the weapon involved was a handgun using shotshell. The injuries caused are described and the ballistic characteristics of the weapons are studied. Such weapons, which are relatively easy to obtain, are not as innocuous as they may appear, since they may be modified either by changing the barrel or by removal of the device inside the barrel which is intended to prevent the firing of solid slugs. PMID- 8006616 TI - Homicide among black males in Jefferson County, Alabama 1978-1989. AB - This study examined 1505 of 1573 (96%) homicides occurring in Jefferson County, Alabama, between 1978 and 1989, that were investigated by the Coroner/Medical Examiners' Office. During this 12 year period, Jefferson County's average annual homicide rate was 18.9 per 100,000 compared to an 11.3 per 100,000 State of Alabama's rate and a 9.3 per 100,000 US rate. In Jefferson County, the average annual homicide rate among blacks (41.4) was almost six times the rate among whites (7.1). The highest average annual race-specific homicide rate was in black males (75.9), followed by black females (12.4), white males (10.4) and white females (4.1). Black males in the 25-34 year age group had the highest rate (159.7), followed by black males in the 35-44 year age group (151.7) and then by black males in the 15-24 year age group (96.2). These rates ranged from almost eight to over eleven times the rates of similarly aged, black females or white males and were over 33 times higher than the rates for white females of the same age. Our results emphasize the high rates of black male on black male violence, the acquaintance of the black male victim and perpetrator, and the importance of arguments as an inciting event. Moreover, we determined that while the raw numbers and rates for black homicides were and are staggering, the average annual homicide rate for black males was actually declining at a greater rate than for all other race-sex groups. Further, our results suggest that a number of hypothesized determinants commonly believed to be associated with the increase in the homicide rate among black males between 15 and 24 years of age, such as drug use, increased availability of firearms and increased child abuse were not, in fact, major determinants of the change in homicide rates. PMID- 8006617 TI - Deaths due to firearms injuries in children. AB - There has been a marked increase in firearms-related deaths in this country over the past several decades. Especially in urban areas this increase has been correlated with a greater availability of handguns. Children have become more common victims of gunfire. Both accidental and homicidal shooting deaths have increased in the lower age groups. We examined deaths due to gunfire in children ten years and younger in Cook County, Illinois, which contains the large city of Chicago. Homicidal shootings predominated in this age group with the most common circumstances being a child struck by a stray bullet. Accidental shooting deaths always occurred when one or more children were playing with a gun they found in the home. PMID- 8006618 TI - Detection of the 4977 base pair mitochondrial DNA deletion in paraffin-embedded heart tissue using the polymerase chain reaction--a new method to probe sudden cardiac death molecular mechanisms? AB - Detection of mitochondrial DNA deletions is performed in fresh or frozen material. At our institute, however, heart samples from subjects referred for autopsy are systematically processed for histologic examination (that is, paraffin-embedded). We were interested to know if mtDNA deletions can be detected in such material. Our data indicate that: 1) the most frequently observed deletion--the 4977 base pair deletion--can easily be detected in paraffin embedded heart tissue; 2) this assay is sufficiently sensitive, since very low levels of the deletion can be found in normal heart tissue from young adults; and 3) buffered formalin appears to be the fixative of choice. Recent literature shows that repeated episodes of ischemia result in the accumulation of mtDNA deletions in myocardial cells. Because ischemic heart disease is a major cause of sudden cardiac death, a sensitive method for the detection of mtDNA damage in myocardial cells will be an important tool to facilitate understanding of unexpected cardiac arrest mechanisms. PMID- 8006619 TI - The significance of morphine concentrations in the cerebrospinal fluid in morphine caused deaths. AB - Morphine analysis was performed using a variety of immunoassay methods in blood, urine and the cisternal cerebrospinal fluid (CSF) from 23 patients dying opiate related deaths. Of these, 16 were a result of intravenous morphine or heroin use. The blood and CSF morphine concentrations were determined using both fluorescence polarization immunoassay (FPIA) and radioimmunoassay (RIA), while urine was analyzed by enzyme multiplied immunoassay technique (EMIT). Urine morphine concentrations were greater than 0.300 microgram/mL in all but one case. Blood and CSF morphine concentrations were found to be poorly correlated, and it was concluded that one should not be used to predict the other. Following intravenous administration, CSF morphine concentrations of greater than 0.02 microgram/mL were however found to be consistent with death from morphine related respiratory depression. As intrathecal or epidural administration of morphine can greatly influence the CSF concentration without inducing respiratory depression, the site of collection of the CSF must be known, as must the route of administration in order to properly interpret CSF morphine concentrations. PMID- 8006620 TI - Analysis of HLA DQ alpha allele and genotype frequencies in populations from Florida. AB - HLA DQ alpha allele and genotype frequencies for Caucasian, African American, Haitian, and Hispanic populations in Florida have been estimated. The Florida laboratories involved in these studies collected donor samples from a variety of sites including clinical laboratories, victim and suspect standards, blood banks, county jail detainees, and laboratory personnel. We have determined that the Caucasian and African American DQ alpha genotype frequencies do not deviate significantly from Hardy-Weinberg expectations and as a result of this heterogeneity analyses, data from the four Florida Caucasian populations may be combined and data from the four Florida African American populations may be combined to form two large HLA DQ alpha genotype frequency databanks. Further, data from the Florida Haitian population may be combined with the Florida African American population. Comparison of the combined Florida Caucasian populations, combined Florida African American populations, the Palm Beach Sheriff's Office (PBSO) Hispanic, and PBSO Haitian population with other databases does not support combination because allele frequency distributions are heterogeneous. PMID- 8006621 TI - Potential forensic applications of minisatellite variant repeat (MVR) mapping using the polymerase chain reaction (PCR) at D1S8. AB - Minisatellite variant repeat (MVR) mapping using the polymerase chain reaction (PCR) at D1S8 (MS32) was applied to samples from various human tissues. All DNA samples obtained from an individual's organs at autopsy consistently gave the same digital diploid codes. Even 1 ng of genomic DNA was sufficient to obtain authentic diploid MVR coding ladders. MVR-PCR could be reliably applied to DNA isolated from bloodstains, saliva stains, seminal stains and plucked hair roots, and should become a powerful tool for individual identification in forensic investigations. PMID- 8006622 TI - Estimation of age at death using cortical histomorphometry of the sternal end of the fourth rib. AB - Given the often fragmentary nature of unidentified human remains, and the importance of using multiple criteria to estimate age at death, it is essential to have a variety of methods that use different anatomical sampling sites. In this study, osteon population densities (OPDs) were determined from transverse sections removed from an area immediately adjacent to the sternal ends of 60 autopsy rib samples. Regression analysis was performed using age at death as the dependent variable and OPD as the independent variable. The results of a "training set/test set" strategy to evaluate the performance of the histological age predicting model indicates that it provides reasonably reliable and accurate age estimates. A multiple regression model using both OPD and the mean age for a rib's morphological age according to the phase method of Iscan et al. [7,8] is also presented. This later age predicting model is recommended when both methods are applicable. PMID- 8006623 TI - Sex determination from the tibia: standards for contemporary Japan. AB - It is vital that skeletal biologists and forensic anthropologists observe populations over time so that changes can be detected and monitored. The purpose of this study is to determine if temporal changes are manifest in the skeleton and, if so, develop appropriate standards to determine sex from the tibia in the contemporary inhabitants of Japan. Osteometric data were obtained from 84 recent Japanese skeletons located at Jikei Medical University, Tokyo. The collection was assembled from the anatomy dissecting room between 1960-1970. With a mean age of about 56 years for males and 51 for females, this sample represents individuals who lived through WWII. Seven tibial measurements were taken and subjected to SPSS-X discriminant function analysis. Results indicated that proximal and distal breadth measurements were selected by the stepwise procedure as the most discriminating. In addition, a number of combinations of measurements were used to develop formulae that would be suitable for fragmentary bones. Average prediction accuracy ranged from 80% from minimum shaft circumference to 89% with proximal epiphyseal breadth. Classification accuracy was higher in males (96%) than in females (79%). Compared with earlier studies of the Japanese, Jikei tibiae are longer, especially in females and thus exhibit less sexual dimorphism. The present research provides new standards that better reflect the Japanese people of today. Furthermore, unlike earlier length based formulae, these results allow sexing from fragmentary bones. PMID- 8006624 TI - Differentiation of truthful and deceptive criminal suspects in Behavior Analysis Interviews. AB - The Behavior Analysis Interview (BAI) is a commonly used procedure designed to assist investigators in distinguishing between suspects who are concealing their involvement in a criminal event (deceptive) from those who are not (truthful). During a BAI a protocol of questions is asked and suspects' verbal responses and accompanying nonverbal behaviors and attitudinal characteristics are assessed. Based on this assessment the likelihood of involvement in the criminal event is determined. The purpose of this study was to determine the effectiveness with which trained evaluators were able to distinguish between truthful and deceptive suspects undergoing BAIs. Sixty videotaped interviews, 30 of truthful and 30 of deceptive suspects, were observed by four evaluators, each of whom independently scored suspect's behaviors and attitudes and judged the suspect's truthfulness. The results showed that, excluding inconclusive decisions, evaluators' average accuracy on truthful suspects was 91% and on deceptive suspects, 80%. Suspects' status did not affect confidence of evaluators' decisions but confidence was greater when correct as opposed to incorrect calls were made. Deceptive suspects manifested "theoretically" predicted behaviors and attitudes of "deceptiveness" to a significantly greater degree than did truthful suspects. The BAI appears to be useful for investigative purposes in order to differentiate between suspects who are concealing involvement in a criminal offense from those who are not. PMID- 8006625 TI - Asbestos exposure and cancerphobia. AB - In 48 cases of claims of psychic injury due to asbestos exposure, seven were diagnosed as "cancerphobia". Cancerphobia is a concept primarily used in personal injury cases with little support in the medical community. Analysis of standards for phobia indicates that the term is inappropriate for such legal claims. Phobic reactions are avoidant reactions with panic or intense anxiety on exposure to the phobic stimulus. The cases reviewed indicate lack of psychiatric symptomatology, lack of conformance to accepted standards, and insufficient attention to history- medical and otherwise. This clinical review supports the contention of Simon that cancerphobia is not a credible classification. Skepticism is merited where potential damage awards are limited by minimal physical findings with resultant emphasis on claims of illness phobia, an example being exposure to a toxic substance like asbestos, which may be followed, but not necessarily so, by a variety of adverse consequences. Professional persons should be alert to the misuse of medical concepts in such cases. PMID- 8006626 TI - Use of alternative light source illumination in bite mark photography. AB - Recent investigation regarding the optical properties of human skin has lead to studies measuring autofluorescence, absorption, and reflectance of monochromatic light during exposure both in vitro and in vivo environments. The Stokes Shift deviation in absorbed and reflected light energy that occurs when skin is illuminated by 450 nanometer visible blue light can produce an augmentation in the appearance of pattern injuries when viewed through colored blocking filters. This paper demonstrates a comparison between photographic appearances of several bitemarks inflicted on living and deceased persons to determine the corroborability and usefulness of fluorescent versus full spectrum visibility of bitemark pattern injuries. PMID- 8006627 TI - Deduction of the order of sexual assaults by DNA analysis of two condoms. AB - Differential DNA extraction procedures were performed on two condoms found at a rape scene. One of the condoms was recovered intact (A), while the second condom (B) had apparently ruptured during the alleged attack. Two related suspects (cousins 1 & 2) were identified as the potential semen donors. Condom B contained DNA from the female and from one of the suspects. Condom A contained DNA from the suspect identified on condom B and from an unidentified individual. The presence of DNA from suspect 2 on both condoms led to the deduction that his sexual activity preceded that of the unidentified suspect. The ability to determine such a sequence of events using DNA typing is unusual. PMID- 8006629 TI - The isolation and identification of lysergic acid diethylamide (LSD) from sugar cubes and a liquid substrate. AB - This report describes a simplified extraction technique for the analysis of LSD by GC/MS. The South Carolina Law Enforcement Division Forensic Laboratory recently received two suspected LSD cases involving four sugar cubes and seven food coloring bottles each containing a liquid substance. Following the extraction described in this report, both cases were subsequently confirmed by GC/MS and quantitated by HPLC. PMID- 8006628 TI - Significant fiber evidence recovered from the clothing of a homicide victim after exposure to the elements for twenty-nine days. AB - An adhesive tape lint removal roller was used to isolate fibers from a homicide victim's clothing that had been exposed to the elements for twenty-nine days. Comparison microscopy, microspectrophotometry, and infrared analysis were used to compare recovered fibers to known fibers obtained from the suspect's shirt and the car in which it was believed the homicide occurred. Fibers recovered from the victim's clothing included specimens that were indistinguishable from fibers constituting the suspect's shirt, and others that were indistinguishable from the three distinct types of fibers comprising the upholstery, carpeting, and trunk liner of the car. The distribution of fibers on the various garments helped corroborate the crime scenario. PMID- 8006630 TI - Death investigation after the destruction of evidence. AB - Unavailable in the literature is any reference to an investigation of death after evidence has been destroyed. In this presentation two firearms and the bullet were melted after the death was certified as a suicide. A team of investigators conducted a psychological autopsy as well as shot patterns to determine the distance from the gun muzzle to the head to determine whether or not the wound was a contact type. The resolution of the case is discussed and the factor of local politics and case prominence in the media is reviewed. PMID- 8006631 TI - A fatal case of trichlorofluoromethane (Freon 11) poisoning. Tissue distribution study by gas chromatography-mass spectrometry. AB - A case of lethal poisoning due to trichlorofluoromethane (FC11) inhalation is described. The fluorocarbon was determined in biological tissues by headspace gas chromatography-mass spectrometry. FC11 was detected in all the examined tissues, with decreasing levels in heart, lung, brain, liver, blood, kidney, and spleen. The highest concentration measured in heart could be related to the mode of toxic action of fluorocarbons postulated by many authors, characterized by the sensitization of the myocardium to the catecholamines producing arrhythmia and cardiac arrest. Nevertheless the aspecific picture of the anatomo-pathological and histological findings does not exclude that the described accidental fatality may have been caused by the combination of direct from toxicity with hypoxemic asphyxiation, due to the saturation of the atmosphere by FC11 in the closed environment in which the intoxication occurred. PMID- 8006632 TI - Can microorganisms produce alcohol in body cavities of a living person?: a case report. AB - Unusual endogenous ethanol production in intraabdominal bloody fluid of an individual who was stabbed in the abdomen and who developed peritonitis after a peritoneotomy is discussed. In the intraabdominal bloody fluid, 2.45 mg/g ethanol and 0.079 mg/g n-propanol were detected. The level of ethanol in the heart blood was about 1 mg/g. The level of n-propanol indicates that a large quantity of ethanol was produced endogenously in the intraabdominal bloody fluid. In an animal experiment in which rats were injected with 20 mL of 10% glucose mixed 5:1 with a presumed volume of rat blood into the abdominal cavity after injury of the small intestine to allow enterobacteria to spread into the cavity, a significant quantity of ethanol was produced in the administered fluid while the animals were alive. The antemortem ethanol production in the intraabdominal bloody fluid of the victim might have been caused by the microorganisms responsible for the peritonitis after the operation. PMID- 8006633 TI - Polymerase chain reaction can resolve some undefined cases of hepatitis B virus antigenic subtyping. AB - HBsAg subtypes were defined by means of adsorbed polyclonal antisera; however, HBsAg subtyping is currently usually carried out with monoclonal antibodies (Mab). We developed a complementary subtyping method based on the polymerase chain reaction. Reference samples belonging to all known HBsAg subtypes could be detected and grouped into four different categories (ayw1/ayw4/ayr, ayw2/ayw3, adw2/adrq+/adrq-, adw4). Thirteen HBsAg-positive serum samples previously subtyped as ad by means of monoclonal antibodies fell into the adw2/adrq+/adrq- group, as well as 13 ay samples into the ayw2/ayw3 group. These results could be confirmed by means of reference polyclonal antisera in nine ad cases (all adw2) and in seven ay cases (all ayw3); the remaining seven were below the detection limit of the polyclonal assay. Four samples which were not recognized by any of the d/y subtype-specific Mab were shown to contain ayw2/ayw3 sequences. Only one contained sufficient HBsAg to be confirmed as ayw3 by means of reference antisera. Three of five sera showing simultaneous reactivity both for d and y specific Mab were classified as adw4 by PCR, as was one by reference polyclonal antisera. The y-specific monoclonal antibody cross-reacted with the adw4 subtype. Single adw2 sequences were amplified in one of the remaining two cases, as well as single ayw2/ayw3 sequences in the other, suggesting that they showed true coexistence of two strains of different subtype, only one of which was in active replication state. It is concluded that the method described is useful in the solution of some undefined cases obtained with the monoclonal-based assays. PMID- 8006634 TI - Dengue virus infects mouse cultured neurons but not astrocytes. AB - Cultures of mouse brain cells containing a high proportion either neurons or astrocytes were inoculated with various strains of dengue virus. At analysis by double immunofluorescence, all strains of dengue virus studied were tropic for neurons. In no case were the astrocytes infected. Only approximately 10% of all neurons were infected, suggesting that the virus may enter the cell through a membrane receptor present only in a subgroup of neurons. PMID- 8006635 TI - Prevalence of antibodies against hepatitis E virus among urban and rural populations in Venezuela. AB - Antibodies against hepatitis E virus (HEV) were detected in sera by a synthetic peptide-based enzyme immunoassay (EIA) from different populations in Venezuela. Antibodies against HEV were found in 1.6% (3/184) of urban pregnant woman (Caracas), in 3.9% (8/204) of rural populations (San Camilo, Edo Apure), and in 5.4% (12/223) of rural Amerindians (Padamo, Edo Amazonas). Positivity was confirmed by a neutralization EIA based on the use of competing soluble free peptides. The prevalence of antibodies in the Amerindian group was significantly higher than in urban pregnant women. No relation was found between age and HEV prevalence in rural populations. Three of 21 positive sera were also weakly positive by Western blot for IgM antibodies. This result, together with the low optical density values observed by EIA, suggested that the presence of antibodies in these sera reflects past infections. Based on these results, Venezuela does not seem to be highly endemic for hepatitis E. This is the first report of serological evidence of infection by HEV in South America. PMID- 8006637 TI - Brief report: sexual transmission of hepatitis C. PMID- 8006636 TI - Radioimmunoprecipitation in the diagnosis of chronic active Epstein-Barr virus infection. AB - Chronic active Epstein-Barr virus (EBV) infection occurs sporadically in a small fraction of individuals infected with EBV. A clear definition of the disease and an unambiguous diagnostic test are still lacking. In an attempt to identify a serologic marker to facilitate the diagnosis, immunoblot and radioimmunoprecipitation assay (RIPA) were compared with standard immunofluorescence on 39 available sera. Results by RIPA revealed that antibodies to a 120 kDa viral protein correlated with the presence of chronic active EBV infection; these antibodies were not detected in sera from other EBV-seropositive individuals, with the exception of one of two patients with ataxia telangiectasia. Also, RIPA was the most sensitive technique for detecting EBV antibodies in sera weakly or doubtfully positive for antibody to EB viral capsid antigen by indirect immunofluorescence. All these sera had antibodies to the 150 kDa protein, also known as p160, the major viral capsid antigen. PMID- 8006639 TI - Suppression of simian immunodeficiency virus replication in primary peripheral mononuclear cells by antisense RNA. AB - It has been demonstrated that human immunodeficiency virus (HIV) replication can be effectively blocked by an antisense sequence that was introduced into the lymphoid cell line through retroviral-mediated gene transfer. In this study, it is demonstrated that antisense RNA can also inhibit simian immunodeficiency virus (SIV) replication in the peripheral blood mononuclear cells (MNCs) of healthy donors. MNCs were transduced with amphotropic recombinant virus encoding either sense or antisense constructs of SIV DNA fragments. After challenge with SIV, the viral replication was suppressed in the antisense-recombinant virus-transduced MNCs compared to sense-recombinant virus-transduced and untransduced MNCs. These data indicate that amphotropic retroviral vectors can be used to introduce antiviral factors (antisense sequence) into human primary MNCs and render them resistant to viral replication. PMID- 8006638 TI - Inhibition of human immunodeficiency virus type 1 replication by nonionic block polymer surfactants. AB - Eight block copolymers of hydrophilic polyoxyethylene and hydrophobic polyoxypropylene were examined for their effects on the replication of human immunodeficiency virus type 1 (HIV-1) in H9 cells. Although the polymers decreased cellular replication, they did not appear to be toxic to the cells; rather, they seemed to arrest cellular growth. Three triblock copolymers were found to inhibit HIV replication at low concentrations. Maximum inhibition was achieved at concentrations of 50 micrograms/ml by day 5 following infection. The combination of azidothymidine with both HIV-1-inhibitory and noninhibitory copolymers resulted in antagonistic effects, with an increase in viral replication, compared to treatment with copolymers or azidothymidine alone. These copolymers should be useful in the study of the mechanism of HIV replication in cell cultures and may yield clinically useful compounds in combination therapies for HIV infection. PMID- 8006640 TI - Typing of human papillomaviruses in condylomata acuminata from Greece. AB - DNA samples from recurrent condylomata acuminata biopsies of Greek males and females were examined for the presence of human papillomavirus (HPV) DNA using high-stringency Southern blot hybridization analysis. Of the twenty-six biopsies, 25 were positive for the HPV 6/11-related DNA sequences, and when further analyzed with the polymerase chain reaction (PCR) the HPV-negative biopsy was also positive for HPV 6/11 DNA. Nineteen specimens were further characterized based on their Pstl restriction endonuclease hybridization pattern. Twelve biopsies were positive for HPV 6a, one biopsy was positive for HPV 11a, and one biopsy was positive for HPV 6c DNA. Three specimens contained HPV 6/11 related DNA that gave an unusual Pstl pattern, and one specimen appeared to represent a multiple HPV infection containing HPV 6/11- and HPV 31/35/39-related sequences. Finally, one sample contained a mixture of HPV 6a DNA and an HPV 6a-like genome. Biopsies were also taken from adjacent apparently normal tissue, 0.5 cm away from the lesion, in 19 of the patients. Only one of these was found to be positive for HPV 6a DNA by Southern blot analysis. PMID- 8006641 TI - Detection of herpes simplex virus DNA sequences in human blood and bone marrow cells. AB - Herpes simplex virus type 1 (HSV1) establishes latent infections in neural tissues of humans and experimental animals. Utilizing a sensitive polymerase chain reaction (PCR) assay we detected HSV DNA sequences in blood cells of healthy prospective bone marrow transplant (BMT) donors and patients. In three healthy individuals studied, HSV DNA sequences were found in all blood cell types and also in bone marrow cells as well as in stem cell progenitor colonies isolated from in vitro cultures. Studies of BMT donor-recipient pairs suggested that HSV reactivation may occur in hematopoietic cells after transplantation, as the PCR signal intensity increased over time simultaneous with an increased antibody titer to HSV. In a mouse model for HSV infection, HSV DNA sequences were found in blood and bone marrow cells at the latent stage of infection, after intravenous (IV) inoculation, but not after ocular inoculation. These studies suggest that bone marrow cells may be an additional site of HSV latency capable of reactivation after BMT. These studies have broad implications for understanding pathogenesis of HSV disease and are of particular significance in situations where allogeneic bone marrow cells are given therapeutically. PMID- 8006642 TI - Analysis of integrated hepatitis B virus DNA and flanking cellular sequences in a childhood hepatocellular carcinoma. AB - The DNA of tumor tissue K1 obtained at autopsy from a case of hepatocellular carcinoma (HCC) in a 9-year-old boy contained integrated hepatitis B virus (HBV) DNA at a single site in the chromosome (case 2, Chang et al.: Hepatology 13:316 320, 1991). To characterize further the integrated viral DNA sequences, a genomic library of the K1 DNA was constructed in the lambda L47.1 vector. One phage clone, designated KTM-1, containing integrated HBV DNA and cellular flanking sequences was obtained from this library. The restriction map and DNA sequence of this clone showed that the integrated HBV DNA was partially deleted and rearranged. The most conserved viral DNA sequences were surface and X genes and arranged in the opposite orientation. The viral core gene was not present. Using chloramphenicol acetyltransferase (CAT) assay, the C-terminal truncated X open reading frame was demonstrated to retain its trans-activating ability. The result suggested that the functional integrated X gene may play a role in hepatocarcinogenesis. The study also showed that the right cellular flanking sequences were human alphoid repetitive sequences. PMID- 8006643 TI - Detection of hepatitis C viral sequences in formalin-fixed, paraffin-embedded liver tissue: effect of interferon alpha therapy. AB - To determine the effect of interferon-alpha (IFN) therapy on hepatitis C virus (HCV) in liver, reverse transcription "nested" polymerase chain reaction (RT-PCR) was applied to detect HCV RNA in formalin-fixed, paraffin-embedded liver biopsy specimens obtained before and at the end of IFN therapy in 42 patients with chronic HCV infection. Results were correlated with the clinical and biochemical outcome in 36 cases. Fifteen patients were nonresponders to IFN; 13 patients had a complete response to IFN but relapsed shortly after IFN was stopped (responders who relapsed); and 8 patients showed a complete and sustained response to IFN therapy (sustained responders). Total RNA was extracted using proteinase K digestion and phenol/chloroform/isoamyl alcohol extraction, and HCV RNA was detected by standard RT-PCR using primers from the highly conserved 5' untranslated region. HCV RNA was detected in 41 of the 42 pretreatment specimens. Of the 36 patients with paired posttreatment samples, HCV RNA was detected in all 15 patients who did not respond to IFN and 9 of 13 who responded to IFN but relapsed shortly after IFN was stopped. In contrast, only one of the eight patients who had a sustained response to IFN therapy had HCV RNA detected by RT PCR (P < 0.04). These data confirm 1) the feasibility of detecting HCV RNA in formalin-fixed, paraffin-embedded tissue from patients with chronic HCV infection, 2) show that sustained response to IFN is associated with loss of liver HCV RNA at the end of IFN therapy, and 3) offer an explanation for recurrence in patients who relapse. PMID- 8006645 TI - Hepatitis type E in Italy: a seroepidemiological survey. Study Group of Hepatitis E. AB - The seroprevalence of antibodies to HEV was determined in three different Italian populations (volunteer blood donors, normal healthy individuals, and intravenous drug users [IVDUs]). The seroprevalence in the populations ranged from 0.74% to 1.94%, with higher rates among IVDUs and individuals over 40 years of age. None of 35 patients diagnosed with acute hepatitis A but 10 of 153 (6.5%) patients with acute nonA, nonB, nonC hepatitis were found to be positive for anti-HEV antibody. One of these antibody positive cases was linked to travel, while the remaining 9 were not associated with travel to endemic areas. These data suggest a possible low circulation of HEV in Italy. PMID- 8006644 TI - Oral famciclovir against duck hepatitis B virus replication in hepatic and nonhepatic tissues of ducklings infected in ovo. AB - Detection of hepadnaviral DNA in extrahepatic tissues of human and animal models of hepatitis B virus (HBV) has raised the question of whether virus replication in organs other than the liver could be targeted for the treatment of chronic hepatitis B. Since duck hepatitis B virus (DHBV) replication is dynamic in the liver, kidney, pancreas, and spleen of newly hatched ducklings infected in ovo, we used the duck model and the new antiherpesvirus agent, famciclovir (FCV), to determine whether antiviral effect of nucleoside analogues on DHBV replication is pluripotential. Day-old ducklings hatched from eggs laid by a DHBV-carrier duck were bled and administered FCV (25 mg/kg/bd) orally for periods of 1, 2, 3, 6, 9, and 12 days. Seventeen (17) hours after the last dose of each regimen the duckling(s) was bled and postmortem samples of liver, kidney, pancreas, and spleen were snap-frozen and stored at -70 degrees C. Analysis of plasma samples of ducklings treated for 2 days and longer by dot-blot hybridisation showed that levels of DHBV DNA were reduced significantly compared to levels in samples collected before treatment begun. Southern blot hybridisation of tissue DNA corroborated these results and showed that DHBV DNA replicative intermediates in all the tissues examined were reduced to levels that reflected the amount of virus released into the blood of each treated duckling. It is concluded from these results that if antiviral agents could be transformed to active metabolites in any infected tissues including the liver, replication of hepadnaviruses would be inhibited.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8006646 TI - Economic change and health service reform: likely impact on teaching, practice, and research in neurology. PMID- 8006647 TI - A multicentre comparative trial of sodium valproate and carbamazepine in adult onset epilepsy. Adult EPITEG Collaborative Group. AB - The long-term efficacy and safety of sodium valproate and carbamazepine in adult outpatients with newly diagnosed primary generalised or partial and secondarily generalised seizures were compared in a randomised, open, multicentre study at 22 neurology outpatient clinics. Patients were randomised to oral sodium valproate (Epilim EC enteric coated 200 mg tablets twice daily, n = 149) or oral carbamazepine (100 mg twice daily increasing to 200 mg twice daily in week 2, n = 151) and followed up for three years. If clinically necessary, dosages were regularly increased until seizures were controlled or toxicity developed. Sodium valproate and carbamazepine controlled both primary generalised and partial seizures equally effectively overall. Significantly more patients on sodium valproate than carbamazepine (126/140 (90%) v 105/141 (75%), p = 0.001) remained on randomised treatment for at least six months. Skin rashes occurred significantly more often in carbamazepine recipients than in sodium valproate recipients (11.2% v 1.7%, p < 0.05) and carbamazepine was associated with a higher withdrawal rate because of adverse events (15% v 5% on sodium valproate) in the first six months of treatment. There was no difference between the drugs in the rate of withdrawal because of poor seizure control at any stage, regardless of seizure type. At the end of the three year trial period, over 70% of the available patients were still on randomised treatment or had recently stopped treatment after achieving full seizure control. Sodium valproate and carbamazepine were both associated with a high degree of overall seizure control regardless of seizure type and both have good long-term tolerability in adult patients with newly diagnosed epilepsy. Recommendations are made for a higher initial dosage regime for sodium valproate in partial seizures. PMID- 8006648 TI - Francois Magendie (1783-1855). PMID- 8006649 TI - Sensory neuropathy in hereditary spastic paraplegia. AB - A large kinship is reported with dominantly inherited spastic paraplegia starting in the first decade of life; its clinical evolution was indistinguishable from that of "pure" hereditary spastic paraplegia (HSP). However, all patients studied had electrophysiological evidence of a predominantly sensory polyneuropathy, which was confirmed on nerve biopsy in three. The histological findings indicated virtually complete loss of large diameter fibres with relative preservation of small myelinated and non-myelinated fibres. The neuropathy was largely asymptomatic and there were no trophic ulcers. This family represents a distinct entity which differs from other reported cases of HSP with neuropathy by virtue of the clinical predominance of the pyramidal syndrome, the greater impairment of large fibre sensory modalities than of pain or temperature modalities, and the consequent absence of mutilation. PMID- 8006650 TI - Association of Lhermitte-Duclos and Cowden disease: report of a new case and review of the literature. AB - Lhermitte-Duclos disease is a rare entity, and its pathological features are unique. Pathological findings are characteristic of the disease, with global hypertrophy of the cerebellum, coarse gyri, and the typical "inverted cortex" pattern. Several associated lesions were noted in many patients with Lhermitte Duclos disease. It is only recently that an association between Lhermitte-Duclos disease and Cowden disease was reported. Cowden disease, or multiple hamartomas syndrome, is a familial disease associating breast cancer, cutaneomucous tricholemmomas, and various other tumoural and dysplasic conditions. A new case of Lhermitte-Duclos disease associated with Cowden disease is reported. A review of the literature found 72 cases of Lhermitte-Duclos disease; 26 had conditions suggesting Cowden disease and seven were definite cases of Cowden disease. The association of Lhermitte-Duclos disease and Cowden disease is probably underestimated. Cowden disease represents a new form of phakomatosis; Lhermitte Duclos disease may occur as a sporadic disease, or as part of familial Cowden disease. The possibility of preneoplastic states in Cowden syndrome stresses the importance of a thorough screening when Lhermitte-Duclos disease is diagnosed. PMID- 8006651 TI - Antibiotic induced meningitis. AB - Three patients with antibiotic induced meningitis, one following penicillin with seven episodes, are reported on--the first well documented description of penicillin induced meningitis. In this patient episodes of headache and nuchal rigidity appeared with and without CSF pleocytosis. Two patients had a total of five episodes of antibiotic induced meningitis after trimethoprim sulphamethoxazole (co-trimoxazole) administration. The features common to all three patients were myalgia, confusion and low CSF glucose. CSF analysis was not a reliable method to differentiate antibiotic induced meningitis from partially treated bacterial meningitis. PMID- 8006652 TI - Minor head injury: pathophysiological or iatrogenic sequelae? AB - This study addresses the possibility that cognitive sequelae--albeit of a transient or minor character--can be associated with mild head injury. Twenty men (aged 16-30 years of age), whose post-traumatic amnesia did not exceed eight hours, were examined within 48 hours of their accident and again one month later. This unselected sample had no previous history of head injury. A control group of 20 men of similar socioeconomic background, was selected from medical wards (where they had been admitted for orthopaedic treatment or a minor operation). They were also retested one month after the first examination. Neuropsychological tests were selected to measure abilities often compromised after significant head injury, namely memory and attention. The experimental component consisted of the fractionation of a complex skill (paced addition) to probe for deficits at different stages of information processing: perception and input into storage; search for and retrieval of information from working memory; and paced and unpaced addition. In general, no significant difference was found between the experimental and control groups, with the possible exception of an initial decrement on two working memory tasks: probe digits and a keeping track task (where the subject has to keep in mind and update a number of variables at the same time). The keeping track paradigm, ostensibly of ecological relevance, may well be worth further exploration in memory research, and in studies of more severely head-injured patients. It is further suggested that the appropriate management and counselling of mildly head-injured patients may help to avert symptoms that are of psychological rather than pathophysiological origin. PMID- 8006653 TI - Jugular venous desaturation and outcome after head injury. AB - Early experience with continuous monitoring of jugular venous oxygen saturation (SjvO2) suggested that this technology might allow early identification of global cerebral ischaemia in patients with severe head injury. The purpose of the present study was to examine the relationship between episodes of jugular venous desaturation and neurological outcome. One hundred and sixteen severely head injured patients had continuous monitoring of SjvO2 during days 1-5 after injury. Episodes of jugular venous desaturation (SjvO2 < 50% for more than 10 minutes) were prospectively identified, and the incidence of desaturation was correlated with neurological outcome: 77 episodes of desaturation occurred in 46 of the 116 patients; 27 had one episode and 19 had multiple episodes of desaturation. The causes of these episodes were systemic (n = 36), cerebral (n = 35), or both (n = 6). Most of the episodes were less than 1 hour in duration, and it is probable that many of them would not have been detected without continuous measurement of SjvO2. Episodes of desaturation were most common on day 1 after injury, and were twice as common in patients with a reduced cerebral blood flow as in patients with a normal or elevated cerebral blood flow. The occurrence of jugular venous desaturation was strongly associated with a poor neurological outcome. The percentage of patients with a poor neurological outcome was 90% with multiple episodes of desaturation and 74% in patients with one desaturation, compared to 55% in patients with no episodes of desaturation. When adjusted for all co variates that were found to be significant, including age, Glasgow coma score, papillary reactivity, type of injury, lowest recorded cerebral perfusion pressure, and highest recorded temperature, the incidence of desaturation remained significantly associated with a poor outcome. Although a cause and effect relationship with outcome cannot be established in this study, the data suggest that monitoring SvO2 might allow early identification and therefore treatment of many types of secondary injury to the brain. PMID- 8006654 TI - Diagnostic imaging algorithm for cervical soft disc herniation. AB - MRI with surface coils is currently the preferred method for evaluating degenerative cervical spine disease. The differentiation between soft disc herniation and osteophytic spurs is not always obvious, however, on a 0.5 Tesla unit. The procedure of choice for soft disc herniation, MRI on a 0.5 T superconducting system associated with plain radiography of the cervical spine, in selecting patients for anterior cervical discectomy without interbody fusion (ACD), was evaluated. This prospective study comprised 100 patients with cervical radicular symptoms, not subsiding after conservative treatment. Plain radiographs were obtained for all patients. Patients without spinal instability, spondylosis, or major osteophytes on plain radiographs and without clinical findings of myelopathy underwent MRI (n = 59) on a 0.5 Tesla superconducting system. The other 41 patients underwent CT myelography. On MRI, herniation of a cervical soft disc was seen in 55 patients and the localisation corresponded well with the clinical symptoms. CT myelography showed a foraminal herniation in one of four selected patients with negative MRI. Fifty of 55 patients underwent ACD. All herniations were confirmed at operation, but in two patients there were important foraminal spurs not seen on MRI. It is concluded that 0.5 T MRI combined with plain radiographs offers an accurate, non-invasive test in the assessment of selected patients with cervical radiculopathy. PMID- 8006655 TI - Single photon emission computed tomography in long-term survivors of adult brain tumours. AB - Sixteen patients with primary brain tumours were examined on average eight years after treatment with surgery or whole brain irradiation using standard clinical assessment, CT, a neuropsychological test battery, and single photon emission CT (SPECT) with 99mTc-exametazime. Seventeen lesions were discovered on inspection of SPECT images, 11 with x-ray CT. Quantitative assessment of tracer uptake compared with 16 matched healthy volunteers was consistent with the presence of lesions. Measurement of uptake in brain regions of the hemisphere not containing the primary tumour still showed significant reductions in patients. This may be due to remote direct effects of the tumour or, more likely, to the whole brain irradiation received. Psychometric performance on most tests was significantly impaired in the patient group and was correlated with abnormalities of tracer uptake to relevant brain regions. PMID- 8006656 TI - Long-term prognosis of transient lone bilateral blindness in adolescents and young adults. AB - We describe a group of 14 patients aged 8-38 years at presentation who had one or more sudden transient attacks of bilateral blindness. Eight patients described bilateral blindness as their only symptom whereas six others experienced some mild associated symptoms. Visual loss always developed within seconds and attacks were often precipitated by exercise, stress, or postural change. Of 13 patients available for review, none suffered a major vascular event during a mean follow up of 10 years. When adolescents and young adults present with transient bilateral blindness, investigations are unlikely to reveal a cause and the long term prognosis appears benign. PMID- 8006657 TI - Long-term follow up of dorsal root entry zone lesions in brachial plexus avulsion. AB - The long-term results of 44 patients who underwent dorsal route entry zone (DREZ) lesioning for pain secondary to brachial plexus avulsion are reported with a mean clinical follow up period of 63 months. The postoperative analgesic effect was judged by the patients as being good (greater than 75% pain reduction), fair (25 75% pain reduction), or poor (0-25% pain reduction). With these criteria 35 patients (77%) had continuing good (30 cases, 68%) or fair (five cases, 11%) pain relief at the time of final follow up. Eight cases (18%) had persisting neurological deficits, although these were generally mild. DREZ thermocoagulation is an effective procedure for relieving deafferentation pain. The analgesic effect which is produced in the early postoperative period seems to be maintained in the long-term. PMID- 8006658 TI - Micrographia associated with a parietal lobe lesion in multiple sclerosis. AB - The occurrence of micrographia in a 52 year old women two years after an isolated episode of painful sensory disturbance led to the diagnosis of multiple sclerosis. Her handwriting returned to normal after a course of intravenous methylprednisolone. Previous reports of movement disorders occurring in the context of multiple sclerosis are briefly reviewed. The finding on MRI studies of an enhancing lesion in the dominant parietal white matter supports Kinnier Wilson's suggestion that the anatomical origin of micrographia lies in the cerebral hemisphere rather than the corpus striatum. PMID- 8006659 TI - Isolated hemiataxia after supratentorial brain infarction. AB - Acute isolated hemiataxia is in most cases due to infratentorial (cerebellar) stroke. It has only twice been described in supratentorial stroke--namely, after thalamic infarction and a capsular haemorrhage. Three patients with isolated hemiataxia after a supratentorial brain infarct are described. These patients were seen in a period of five years during which 899 patients with a first supratentorial brain infarct were registered. Clinically the hemiataxia was of the cerebellar type. In two patients, CT and MRI showed a small, deep (lacunar) infarct restricted to the posterior limb of the internal capsule, a site not previously reported in isolated hemiataxia. The third patient had a small, deep (lacunar) infarct in the thalamus extending into the adjacent posterior limb of the internal capsule. Isolated hemiataxia after a supratentorial brain infarct is a very rare clinical stroke syndrome. The cerebellar type hemiataxia was most likely caused by interruption of the cerebellar pathways at the level of the internal capsule. Our cases confirm prior observations that the cerebellar pathways run through the posterior part of the posterior limb of the internal capsule separately from the motor and sensory pathways. PMID- 8006661 TI - Hemiballism-hemichorea and non-ketotic hyperglycaemia. AB - Three patients with hemiballism-hemichorea caused by non-ketotic hyperglycaemia are presented, two of whom had hyperosmolar non-ketotic hyperglycaemic syndrome. In two of the three patients, the hyperkinesia was the initial presenting symptom of their diabetes mellitus. The hypersensitivity of the postmenopausal dopamine receptor, decreased gamma-aminobutyric acid in the brain in non-ketotic hyperglycaemia, coexisting lacunar infarct in the basal ganglion, and pre existing metabolic dysfunction in the basal ganglion may all have played a part in the pathogenesis of this movement disorder. PMID- 8006660 TI - Pure autonomic failure: a new case with clinical, biochemical, and necropsy data. AB - Postmortem examination of a patient with pure autonomic failure showed loss of intermediolateral column cells and of sympathetic ganglionic neurons; there were Lewy bodies in sympathetic neurons. No neuronal loss or Lewy bodies were seen in pigmented brainstem nuclei. This case indicates that pure autonomic failure can occur in the absence of presymptomatic Parkinson's disease. Furthermore, it supports the view that in pure autonomic failure the lesion is more distal than in autonomic failure associated with multiple system atrophy. PMID- 8006662 TI - AL kappa amyloid in a solitary extradural lymphoma. AB - A 68 year old man with a 10 year history of apparently benign IgM kappa paraproteinaemia presented with dysarthria, left hemiparesis, and a sensory peripheral neuropathy. A calcified right temporoparietal extradural mass was shown by scintigraphy with 123I-serum amyloid P component to contain amyloid. There were no extracranial amyloid deposits. Clinical improvement followed craniotomy and partial resection of tissue which consisted of amyloid and a mixed mononuclear cell infiltrate. The amyloid fibrils consisted of the framework 1 region of the variable domain of monoclonal kappa IV immunoglobulin light chains. There was a prominent B-cell clonal immunoglobulin gene rearrangement in the tumour tissue, supporting a diagnosis of lymphoplasmacytic lymphoma, but no sign of systemic lymphoma. Neurological state, tumour volume, and quantity of amyloid have remained static for two years after treatment with chlorambucil. PMID- 8006663 TI - Thecoperitoneal shunt for post-traumatic syringomyelia. AB - A case of post-traumatic syringomyelia developing two years after spinal cord injury is presented. The patient was treated with the placement of a thecoperitoneal shunt incorporating a low pressure valve. Response was excellent with restoration of neurological function and almost complete collapse of the cavity at one year follow up. The rationale of this form of treatment is discussed in the light of recent evidence concerning the pathogenesis of the condition. PMID- 8006664 TI - Transmission of Creutzfeldt-Jakob disease to a chimpanzee by electrodes contaminated during neurosurgery. AB - Stereotactic multicontact electrodes used to probe the cerebral cortex of a middle aged woman with progressive dementia were previously implicated in the accidental transmission of Creutzfeldt-Jakob disease (CJD) to two younger patients. The diagnoses of CJD have been confirmed for all three cases. More than two years after their last use in humans, after three cleanings and repeated sterilisation in ethanol and formaldehyde vapour, the electrodes were implanted in the cortex of a chimpanzee. Eighteen months later the animal became ill with CJD. This finding serves to re-emphasise the potential danger posed by reuse of instruments contaminated with the agents of spongiform encephalopathies, even after scrupulous attempts to clean them. PMID- 8006665 TI - X-linked adrenoleukodystrophy with non-diagnostic plasma very long chain fatty acids. AB - Measurement of plasma very long chain fatty acids is widely recognised as a sensitive screening test for X-linked adrenoleukodystrophy (X-ALD). This test has particular importance because of the highly variable clinical expression of X ALD. In this affected family the progressive childhood form of X-ALD was accompanied by "non-diagnostic" concentrations of plasma very long chain fatty acids. The implications for diagnosis of X-ALD are discussed. PMID- 8006666 TI - Familial Pick's disease and dementia in frontal lobe degeneration of non Alzheimer type are not variants of prion disease. PMID- 8006667 TI - Acute neuromuscular respiratory paralysis. PMID- 8006668 TI - SPECT and MRI findings in Sydenham's chorea. PMID- 8006669 TI - Paraneoplastic opsoclonus-myoclonus syndrome in metastatic ovarian carcinoma. PMID- 8006670 TI - Cervical radiculopathy and bilateral internuclear ophthalmoplegia caused by temporal arteritis. PMID- 8006671 TI - Methylenetetrahydrofolate reductase deficiency revealed by a neuropathy in a psychotic adult. PMID- 8006672 TI - Transcallosal intraventricular tumour excision, alcohol abuse, and amnestic syndrome: a case study. PMID- 8006673 TI - Isolated aneurysm of a spinal radicular artery presenting as spinal subarachnoid haemorrhage. PMID- 8006674 TI - Delirium and quantitative EEG. PMID- 8006675 TI - Management of subarachnoid haemorrhage. PMID- 8006676 TI - Development of spinal cord in the isolated CNS of a neonatal mammal (the opossum Monodelphis domestica) maintained in longterm culture. AB - The CNS of the newly born opossum removed in its entirety survives and maintains its electrical excitability in suitable culture media for up to ten days at 25 degrees C. The structure of the developing neonatal spinal cord has been studied in the intact animal and in the cultured CNS. The differentiation and survival of individual cells and subcellular structures were followed at the light and electron microscopic level. The expression of cell markers in neuronal and glial cells was studied immunocytochemically using commercially available antibodies. Both mono- and polyclonal antibodies raised against antigens from several other species cross-reacted with Monodelphis antigens. The spinal cord of preparations removed from three-day-old-animals showed many neuron specific enolase-positive large neurons in the ventral horn as well as vimentin- and glial fibrillary acidic protein-positive radial glial cells and numerous small diameter unmyelinated axons, abundant dendrites and synaptic structures. From post natal day 5 to post natal day 8 continued differentiation of neurons and differentiation of radial glial cells into astrocytes were apparent. Radial glial fibres and astrocytes reacted positively to antibodies against glial fibrillary acidic protein. Myelin had not appeared at 8 days. A comparison of material obtained from postnatal day 3-postnatal day 4 preparations fixed immediately after dissection and from postnatal day 3-postnatal day 4 preparations fixed after 5 days in culture showed growth with continued mitotic activity of the neuroepithelial cells and further neuronal and glial maturation in the spinal cord especially in the more rostral end. In successful experiments in vitro, the preservation of individual cells, organelles, membranes and synapses was similar in the freshly dissected and cultured preparations apart from a distinct loss of the youngest and some of the oldest neurons in the spinal cord. Also the main fibre tracts (dorsal, lateral and ventromedial funiculus) survived. Virtually all preparations that had not been damaged or injured showed these results. Possible reasons for the death or survival of individual neuronal or glial cell populations in these preparations are discussed. PMID- 8006677 TI - An immunocytochemical marker for hamster retinal ganglion cells. AB - We examined the specificity and developmental time course of the labelling of retinal ganglion cells in Syrian hamsters by a monoclonal antibody AB5. In adult hamsters, AB5 selectively labelled somata in the ganglion cell layer, dendrites in the inner plexiform layer and axons in the nerve fibre layer. When retinal ganglion cells were retrogradely labelled with DiI prior to AB5 immunocytochemistry, all of the retrogradely labelled retinal ganglion cells in the ganglion cell layer were AB5 immunoreactive, indicating that AB5 labels all classes of ganglion cell in that layer. In retinae depleted of retinal ganglion cells by neonatal optic nerve transections, AB5 did not label any somata or processes, indicating that AB5 specifically labels retinal ganglion cells. During development, AB5 labelling first appeared as a weak staining of cell bodies in the ganglion cell layer on postnatal day 12 (P12; PO = first 24 h following birth) and acquired the staining pattern seen in the adult by postnatal day 14. From the onset of AB5 immunoreactivity, AB5-labelled somata of varying sizes were present across the entire retinal surface. Although AB5 labelled retinal ganglion cell axons in the nerve fibre layer of the retina it did not label the optic nerve or retinal ganglion cell axons in the brain at any age examined. AB5 labelling was also found to be compatible with bromodeoxyuridine immunocytochemistry and, therefore, useful for determining the time of generation of hamster retinal ganglion cells. PMID- 8006678 TI - Abnormal astrocyte differentiation and defective cellular interactions in wobbler mouse spinal cord. AB - The wobbler mutation is inherited as an autosomal recessive trait and displays a muscular atrophy associated with motoneuron degeneration in early postnatal development. It has been shown that the level of glial fibrillary acidic protein (GFAP) is greatly increased in the spinal cord of wobbler mice. We performed immunocytochemical analyses combined with confocal microscopy to study the developmental distribution of GFAP-positive astrocytes in the spinal cord of wobbler mice during the course of the disease, and in primary cultures of adult wobbler spinal cord astrocytes. Many changes in the number and distribution of astrocytes were observed in the wobbler mice from 1-10 months post-partum. Strongly GFAP-positive astrocytes are present in small number in the anterior horn by 1 month. They increase in number and are observed in the entire spinal cord grey and white matters by 2-10 months. These reactive astrocytes have thick, short, extensively branched processes which contrast with the long, unbranched processes observed in control mice. The wobbler astrocyte processes are oriented perpendicular to the surface of the spinal cord, which contrasts with the normal parallel, concentric orientation. No expansion of astrocyte processes exit from the white matter towards the grey matter. Moreover, the surface of the wobbler spinal cord beneath the meninges displays a dramatic decrease of interdigitating processes, end feet and flattened cell bodies of astrocytes that form a disorganized layer. In vitro, mutant astrocytes have morphological characteristics similar to those in vivo and, in particular, develop short, thick, branched processes. These mutant astrocytes in cultures do not contact one another, whereas normal mature cultures show an increased incidence of cell-cell contacts between long processes. The increase of astrocyte reactivity associated with these modifications in astrocytic process arrangement may reflect an important primary event in the course of the wobbler disease rather than a non specific response to motoneuronal death. PMID- 8006679 TI - Morphology and distribution of ecto-5'-nucleotidase-positive cells in the rat choroid plexus. AB - The aim of this report was to find out whether adenosine can be produced locally in the choroid plexus of rats. Therefore we investigated the distribution of the enzyme ecto-5'-nucleotidase which hydrolyzes extracellular adenosine monophosphate to adenosine and phosphate. Enzyme activity histochemistry and immunohistochemistry demonstrated that ecto-5'-nucleotidase is present in the stroma but not in the epithelium. The positive cells in the stroma were identified as fibroblasts by their localization and by their shape. Double labelling immunohistochemistry actually showed that ecto-5'-nucleotidase was absent from MHC class II-positive cells and from vessel walls. These data indicate that adenosine may be produced in the choroid plexus, and specifically in the interstitium. From there, adenosine would have direct access to nerves, immune cells, the epithelium and microvessels. Because adenosine has been reported to modulate blood supply and the rate of production of cerebrospinal fluid, a local control mechanism involving adenosine might operate in the choroid plexus in a similar way to that described in other tissues. Effects of adenosine on nerves and immune cells are discussed. The exclusive presence of ecto-5' nucleotidase in the fibroblasts that are in contact with choroid plexus epithelium suggests that the expression of the enzyme is controlled by factors produced by epithelial cells, for instance by extracellular nucleotides. PMID- 8006680 TI - Ultrastructural study on the interaction of insulin-albumin-gold complex with mouse brain microvascular endothelial cells. AB - The interaction between the brain microvascular endothelium and bovine serum albumin complexed with insulin and colloidal gold (insulin-BSA-gold) was studied in adult and newborn mice. The results suggest: (a) the modification of albumin enhances its binding to the luminal front of the endothelial cells, as compared to unmodified albumin used in previous studies from this laboratory; (b) the binding density of insulin-BSA-gold complex to blood-brain barrier microvessels is approximately 2.5 times higher in newborn than in adult mice; (c) in adult mice, fenestrated endothelia of the median eminence and choroid plexus demonstrate the highest binding capacity (over five and two times higher, respectively, than in blood-brain barrier endothelia); (d) in the median eminence only, the gold-labelled tracer particles may be transported across the vessel wall. Our observations offer new ultrastructural evidence that: (1) the modification of BSA molecules by complexing with insulin does not enhance the transport of BSA across the blood-brain barrier in mouse brain, and (2) insulin BSA-gold complex appears adequate for ultrastructural localization of blood-brain barrier insulin receptors but is of questionable value as a tracer for demonstration of increased transendothelial transport in blood-brain barrier microvasculature. PMID- 8006681 TI - Muscle phosphoglycerate mutase (PGAM) deficiency in the first Caucasian patient: biochemistry, muscle culture and 31P-MR spectroscopy. AB - Muscle phosphoglycerate mutase (PGAM) deficiency has been so far identified in only six patients, five of these being African Americans. We report the results of clinical, morphological, biochemical, muscle culture and 31P-MR spectroscopy studies in the first Caucasian patient with muscle PGAM deficiency. A 23-year-old man had a 10-year history of cramps after physical exertion with one episode of pigmenturia. Neurological examination and EMG study were normal. ECG and echocardiography revealed hypertrophy of the interventricular septum and slight dilation of the left chambers of the heart. Muscle biopsy revealed increased glycogen content and some accumulation of mitochondria. Muscle PGAM activity was markedly decreased (6.5% and 9.7% of control value in two different biopsies). Citrate synthase and other mitochondrial respiratory chain enzyme activities were much higher than normal. In contrast to the marked decrease of PGAM activity observed in muscle biopsy, total enzyme activity in the patient's aneural muscle culture was normal, being represented exclusively by BB isoenzyme. The deficiency of PGAM-MM isoenzyme was reproduced in the patient's innervated muscle culture. Muscle 31P-MR spectroscopy showed accumulation of phosphomonoesters only on fast "glycolytic" exercise. On "aerobic" exercise, Vmax, calculated from the work energy cost transfer function, showed an increase consistent with the morphological and biochemical evidence of mitochondrial proliferation. This might represent a sort of compensatory aerobic effort in an attempt to restore muscle power. PMID- 8006682 TI - Reduced cerebellar blood flow and oxygen metabolism in spinocerebellar degeneration: a combined PET and MRI study. AB - Fourteen patients with spinocerebellar degeneration (SCD) were subjected to MRI and PET studies. The quantitative MRI data revealed significant cerebellar and pontine atrophy in the patients with olivopontocerebellar atrophy (OPCA), and cerebellar atrophy in the patients with late cerebellar cortical atrophy (LCCA). We failed to demonstrate significant differences in the pons between LCCA patients and normal controls. PET measurements revealed decreases in cerebral oxygen metabolic rate (CMRO2) in the cerebellar hemisphere and vermis in both groups of patients. The markedly decreased cerebral blood flow (CBF) and CMRO2 in the pons were found only in the patients with OPCA. PET data corrected for the tissue shrinkage on the basis of MRI morphometry indicated a net reduction in cerebellar CMRO2 and CBF. The present study has demonstrated that a combination of functional and anatomical data offers further evidence in favour of the current acceptable classification of SCD based on clinicopathological grounds. Our data further suggest that the amount of atrophy in the cerebellum could not fully account for the decreased metabolic rates observed in PET studies. PMID- 8006683 TI - Differentiating subtotal carotid artery stenoses from occlusions by colour-coded duplex sonography. AB - During a 9-month period the carotid arteries of 2420 consecutive patients were investigated by conventional Doppler and duplex ultrasonography as well as by colour-coded duplex sonography. Of 186 internal carotid arteries showing a diameter reduction at the bifurcation level of 95% or more by conventional techniques, 131 underwent X-ray angiography which revealed a subtotal stenosis in 25 and an occlusion in 106 cases. Using a total of ten criteria for describing the colour-coded duplex findings, the "distal colour filling", a combination of three single criteria, could be found in all subtotal stenoses and none of the occlusions. "Distal colour filling" was diagnosed if a colour signal was present for a length of at least 1.5 cm directly behind an assumed stenosis comprising the whole area between the vessel walls. Our results suggest that non-invasive colour-coded duplex sonography is superior to conventional Doppler and duplex techniques and comparable to invasive X-ray angiography in differentiating extracranial subtotal carotid artery stenoses from occlusions. PMID- 8006684 TI - Magnetic resonance imaging of skeletal muscles in idiopathic inflammatory myopathies of adults. AB - The purpose of the study was to describe typical MRI findings in various types of idiopathic inflammatory myopathies in adulthood and to correlate the MRI with histopathological and electromyographic findings, and the serum creatine kinase (CK) activity. A third goal was to assess the diagnostic value of the use of gadolinium-DTPA (Gd-DTPA). Fifty-eight patients (35 women, 23 men), aged 21-83 years (median age 59 years), suffering from idiopathic myositides (13 with acute and 45 chronic diseases; 25 with polymyositis, 14 with dermatomyositis, 8 with granulomatous and 11 with inclusion body myositides) were examined with MRI. Seventeen of them received an intravenous infusion of Gd-DTPA. Histopathological and MRI findings of 21 muscles of 18 patients were compared. MRI of skeletal muscles showed abnormal signal intensities in 56 (96.6%) of the 58 patients. MRI abnormalities were found more often than elevated CK activity (P < 0.001). The hyperintensity of T2-weighted images was more conspicuous than on T1-weighted images in 26 (44.8%) patients, indicating oedema-like abnormalities. MRI of 50 (86.2%) patients showed fat replacement. In acute myositides, oedema-like abnormalities were more often visible and in muscle lipomatosis less often visible than in chronic diseases (P < 0.05 each). In dermatomyositis oedema-like abnormalities were more and lipomatosis less frequent than in the other types of myositis (P < 0.005) and correlated with the acuteness of the disease.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8006685 TI - Detection of oligoclonal IgA in cerebrospinal fluid samples by an isoelectric focusing procedure. AB - An isoelectric focusing procedure for the detection of oligoclonal IgA in cerebrospinal fluid (CSF) samples is presented. CSF IgA bands were found in 69% of patients with various inflammatory neurological diseases, in 22% of patients with other neurological diseases, but in none of the patients with non neurological diseases. In patients with inflammatory neurological diseases we examined the relationship between an intrathecal synthesis of oligoclonal IgA and an intrathecal IgA synthesis as proved by a formula recently described by Reiber and Felgenhauer: 83% of patients with an intrathecal IgA synthesis according to the formula of Reiber and Felgenhauer also showed CSF IgA bands whereas 59% of patients without an intrathecal IgA synthesis displayed an intrathecal synthesis of oligoclonal IgA. Seventeen percent of patients with inflammatory neurological diseases were characterized by an intrathecal synthesis of oligoclonal IgA but did not show either an intrathecal IgA synthesis or an intrathecal synthesis of oligoclonal IgG, the detection of oligoclonal IgA therefore being the only evidence of an intrathecal humoral immune response in these patients. PMID- 8006686 TI - Kinematic properties of slow arm movements in Parkinson's disease. AB - Present pathophysiological concepts of bradykinesia stress an impairment of fast movements in Parkinson's disease. It is, however, unknown whether "bradykinetic" movements are different from slow movements of normal subjects. We recorded trajectories of unrestrained "natural" arm movements from normal subjects and patients with Parkinson's disease. The experiment required the execution of pointing movements for different movement distances and velocities. The shape of trajectories was found to be changed in Parkinson's disease. The steepness of the initial segment and the relation between steepness of the initial segment and final segment both exceeded corresponding values in normal subjects. An analysis of velocity profiles showed an impaired synchrony of vertical and horizontal velocity components. The difference from normal subjects increased with movement velocity. Parkinsonian patients suffered from a fundamental defect in the composition of complex sequences of motor programs required to perform natural arm movements. PMID- 8006687 TI - A 400-kb tandem duplication within the dystrophin gene leads to severe Becker muscular dystrophy. AB - We describe a family with a large duplication of exons 2-16 of the dystrophin gene. It was characterized by immunocytochemistry, field-inversion gel electrophoresis and quantitative Southern blots. Our observations are of clinical interest in that they demonstrate an intermediate disease course despite a disrupted reading frame of dystrophin as postulated from exon-intron boundaries. We discuss possible mechanisms which may explain the unusual phenotype in our patient. PMID- 8006689 TI - Multiple sclerosis: genetic versus environmental aetiology: epidemiology in Israel updated. AB - The incidence and prevalence of multiple sclerosis (MS) were compared, controlling for age, in native-born Israelis of different origins and in immigrants to Israel. This comparison was carried out in two populations, countrywide and in Jerusalem. In the countrywide population, ascertainment was based mainly on hospitalizations; it included 252 patients who were native-born and 150 who had immigrated from Africa-Asia (AA immigrants). The 89 MS patients of Jerusalem also included patients diagnosed in outpatient clinics. In native born Israelis whose father was born in Europe-America (I-EA), the incidence and prevalence of MS were found to be as high as or even higher than that found previously in immigrants from Europe-America. Among native-born Israelis whose father was born in Africa or Asia (I-AA), the yearly age-adjusted incidence and prevalence rates were found to be 1.4- to 1.8-fold higher than among AA immigrants, pointing to environmental factors. The incidence and prevalence rates in the I-EA were 1.2- to 1.6-fold higher than in the I-AA, pointing to genetic factors. These results seem to point to both environmental and genetic factors in the aetiology of MS. Further research is needed, however, to disentangle the genetic factors from possible environmental differences in the two ethnic groups. PMID- 8006690 TI - Hemiparkinsonism-hemihypertrophy. PMID- 8006688 TI - Cortical reflex myoclonus in patients with the mitochondrial DNA transfer RNA(Lys)(8344) (MERRF) mutation. AB - Five patients from three families with the syndrome of myoclonic epilepsy and ragged red fibres (MERRF), associated with the mitochondrial DNA point mutation at position 8344, were studied neurophysiologically to determine the characteristics of their myoclonus. The findings were those of cortical reflex myoclonus, with enlarged cortical somatosensory evoked potentials and late reflex responses to peripheral nerve stimulation. Electroencephalography showed paroxysmal spike and polyspike and wave discharges, with photic sensitivity. This pattern of electrophysiological abnormalities was uniform, despite considerable variation in severity of myoclonus. Although a consistent finding, cortical reflex myoclonus is not specific to MERRF amongst myoclonic syndromes. PMID- 8006691 TI - A chaos theory approach to autonomic dysfunction in multiple sclerosis. PMID- 8006692 TI - Preserved cortical somatosensory evoked potentials in apnoeic coma with loss of brain-stem reflexes. PMID- 8006693 TI - The ADHA National Research Agenda: white paper by the ADHA 1993-94 Council on Research. PMID- 8006694 TI - A study of oral candidiasis in HIV-positive patients. AB - PURPOSE: Candidiasis may occur as the first clinical sign or symptom of HIV disease. Oral candidiasis was studied with respect to immunological status, and response to antifungal therapy in a group of HIV-positive individuals with a history of recurrent oral candidal infections. METHODS: Yeast cultures were obtained from 16 HIV-positive patients and identified and quantitated on a weekly basis until the infection was controlled. Thereafter, cultures were taken monthly or when recurrences occurred for a minimum of three to a maximum of 15 months. Ketoconazole and fluconazole were administered to control clinical signs and symptoms, which were evaluated by appearance and location in the oral cavity. Culture smears were quantitated by colony-forming units (CFUs) on dextrose agar plates. Individual patient medical histories included current medications, the presence of xerostomia, smoking habits, and denture wear. Frequency data only are reported due to the small number of patients included in the study. RESULTS: The presence of clinical lesions coincided with increased colony-forming units, and a combination of pseudomembranous and erythematous lesions was the most prevalent. Frequently, a patient's lesions had the same clinical appearance as previous episodes involving the same oral sites. However, the presence of Candida cannot be accurately assessed by clinical signs alone since high CFU counts were found in patients demonstrating no clinical signs or symptoms. CONCLUSIONS: An increasing yeast burden in the oral flora may result from a combination of local factors such as smoking, xerostomia, antibiotic or antiviral medication, and decreasing cell mediated immunity leading to immune tolerance towards Candida. Negative cultures following antifungal treatment most likely reflect a diminished yeast population rather than eradication of Candida. Subclinical Candida in the oral flora warrants consideration in prophylactic treatment options for the HIV positive patient. PMID- 8006695 TI - Michigan hospice oral healthcare needs survey. AB - PURPOSE: Very little research has been conducted about the state of oral healthcare for the terminally ill in Michigan hospice programs. The purpose of this study was to assess the oral healthcare services currently being provided by caregivers in Michigan hospice programs and to determine the needs for oral healthcare in-service training for nurses, home health aides, and volunteers who may provide basic oral care. METHODS: In October 1991, a four-page questionnaire was mailed to the patient care coordinators of the 90 hospice programs listed in the 1990/1991 Michigan Hospice Organization Directory. Frequency data were compiled for each question. RESULTS: Coordinators from 50 programs responded for a 56% response rate. Results showed that 100% of nurses and aides and 88% of volunteers were providing oral healthcare for clients. Some services, such as oral cleansing and denture care, were more likely to be provided by aides or volunteers. Referrals to dental professionals, and palliative measures for relief of pain or other oral symptoms, were more likely to be provided by nurses. Sixty percent of patient care coordinators reported that the amount of oral healthcare in-service information being received by caregivers was less than sufficient. Only 6% of hospice programs reported using a dentist or dental hygienist as in service presenters. Eighty-seven percent of hospice programs surveyed had no written oral healthcare protocol. Eighty percent of patient care coordinators stated that clients or their families express concerns about oral health needs at least occasionally. Eighty-three percent stated that hospice staff assess client oral conditions at least occasionally and 92% agree that oral care is important to clients. CONCLUSIONS: Although a wide range of oral healthcare services are being provided for terminally ill clients in Michigan hospice programs by nurses, aides, and volunteers, the majority of providers may not receive adequate information to provide complete and effective services. Based on these results, it is recommended that the dental hygienist take a leadership role in providing oral health information to hospice caregivers. PMID- 8006696 TI - Data systems, data sets, and work transformation. PMID- 8006697 TI - Making the hidden obvious. Management education through survey feedback. AB - Staff nurse perceptions of the work setting are powerful indicators of job satisfaction and often guide intent to remain or leave the job. In this study, staff nurse perceptions of the unit work environment were disclosed to nurse managers in an innovative management education strategy. Equipped with unit specific information from their staff members, nurse managers found that they were better able to address the factors identified as most important. Use of survey-based information promoted better management decisions and a higher level of confidence. PMID- 8006698 TI - Use of home health services by elderly persons with cognitive impairment. AB - Individuals with cognitive impairment are at high risk for institutionalization; thus, they may benefit from the support provided by home health services. The authors studied a cohort of elderly persons admitted to a home health agency, after first assessing them for cognitive impairment. Comparisons were made between cognitively impaired and cognitively intact individuals. Significant differences in the volume and type of services used were found. Management issues for home health agencies are raised. PMID- 8006699 TI - Sexual harassment of female registered nurses in hospitals. AB - Sexual harassment of nurses seriously affects nursing performance and productivity. In this survey, sexual harassment by male patients and coworkers was reported by greater than 70% of the female staff nurses surveyed. The most common manifestations of harassment were sexual remarks; however, behaviors involving touch were frequent. Nurses noted that they often confronted patients when these behaviors occurred, but were less likely to confront male co-workers. Findings suggest that nursing managers and executives must discover and eliminate sexual harassment in hospital work settings and create work cultures that discourage manifestation of sexually harassing behaviors. PMID- 8006700 TI - Managers as nurse advocates. A double-edged sword. PMID- 8006701 TI - Management development: preparing nurse managers for the future. Part 1, Program model. AB - Nurse executives need to develop programs to help nurse managers meet rapidly changing role expectations and prepare for new healthcare challenges. This two part series reports on one such program for nurse managers at The Johns Hopkins Hospital. Part 1 describes the program model, its conceptual framework, and its various components. Part 2 will present an in-depth evaluation of the program and recommendations for future development. PMID- 8006702 TI - The effectiveness of personal emergency response systems in meeting the safety monitoring needs of home care clients. AB - Personal emergency response systems (PERS) are electronic communication devices placed in the home to summon help in an emergency. In 1988, New York enacted legislation providing for Medicaid reimbursement for patients of certified home health agencies (CHHAs) whose PERS substituted for hours of safety monitoring by a personal care worker as part of the plan of care. Before the implementation of the new legislation, the Visiting Nurse Service of New York initiated a grant funded demonstration project in February 1992, which showed that PERS save lives, reduce healthcare costs, and are well received by patients. The authors discuss the issues and outcomes surrounding the use of PERS within a CHHA. PMID- 8006703 TI - The cost of shared governance. PMID- 8006704 TI - CNS-directed case management. Cost and quality in harmony. AB - Preserving the integrity of high quality care in a financially restricted environment is the primary challenge facing healthcare providers. The critical question is which delivery system will use limited resources most efficiently without jeopardizing quality of care? Case management has been identified as a solution that offers the most promise. The case management model at Sioux Valley Hospital was developed to deal proactively with resource-intensive patients with chronic illnesses who have frequent admissions and who create financial risk for the hospital. The authors describe the fiscal and clinical outcomes of these select patients. PMID- 8006705 TI - Recruitment and retention in maternity nursing. PMID- 8006706 TI - Motivating the nursing staff. PMID- 8006707 TI - Differentiated interdisciplinary practice. AB - Differentiated nursing practice (DNP) has demonstrated positive outcomes for patients, practitioners, and healthcare organizations. By expanding the principles of DNP to an interdisciplinary model, members of the oncology program of Indiana University Medical Center found that these outcomes were magnified. Patients' access to healthcare services improved, as did their efficacy in self care behaviors; practitioners reported improved role satisfaction and use of fellow team members; and lengths of hospitalization and premature readmissions were reduced. PMID- 8006708 TI - Is governance being shared? AB - Chief nurse executives from acute care general hospitals selected the "most professional/innovative" nursing unit in their institutions and indicated which level in the nursing hierarchy was responsible for selected activities and decisions about the content and context of practice on that unit. Responses from 220 executives raise interesting issues regarding the sharing of governance between administrators and staff registered nurses. PMID- 8006709 TI - Information technology survey. PMID- 8006710 TI - The Center for Nursing Leadership. PMID- 8006711 TI - Sponsored professionals in the United States: employment considerations. PMID- 8006712 TI - Pharmacokinetic characterization of menaquinone-4 in dogs by sensitive HPLC determination. AB - A simple and sensitive assay method for a pharmacokinetic study of Menaquinone-4 in dogs was established using HPLC with fluorescence detection following extraction with organic solvent. The quantification limit of this method was 1 ng/ml of plasma. A new oily solution formulation of Menaquinone-4 was administered orally to nonfasted dogs at doses of 0.4, 4 and 40 mg/kg. The plasma concentrations reached maximum levels at 1 to 1.5 h after dosing, and then decreased slowly. AUC values up to 24 h after administration were almost dose proportional. Menaquinone-4 was also administered to dogs in soft-capsules, for comparison with a conventional hard-capsule oral formulation and an intravenous lecithin formulation. The mean AUC for oral dosing in the soft-capsule formulation was 13.5% of that for intravenous dosing in lecithin, and was 4.6 times higher than that for oral dosing in hard-capsules. Additional dosing in fasted dogs indicated that the AUC in pre-fed dogs was about 4 times higher, suggesting that feeding before giving Menaquinone-4 raises the bioavailability. Overall Menaquinone-4 was absorbed rapidly after administration in non-fasted dogs and dose-proportional bioavailability was obtained among the doses of 0.4 to 40 mg/kg. Higher plasma concentrations were observed after administration in the soft-capsule formulation rather than in the hard-capsule formulation. These findings suggest that the soft-capsule formulation would show a good pharmacokinetic profile for elderly patients with osteoporosis. PMID- 8006713 TI - Effects of dietary n-3 and n-6 fatty acids on liver and erythrocyte lipids in streptozotocin-induced diabetic rats. AB - Streptozotocin-induced diabetic and control rats were placed in one of two dietary groups and fed diets with a P/S ratio of 2.2-2.3 for 4 weeks. The n-3/n-6 ratios in the dietary groups were 0.01 (SAF group) and 2.92 (PER group). A decrease in the 20:4n-6 level, and an increase in the 18:2n-6 level were observed in the erythrocyte lipids of diabetic rats of both dietary groups, as compared with the levels in control rats. The cholesterol/lipid-P ratio in erythrocyte lipids was significantly higher in diabetic rats than in control rats in both dietary groups, while the ratio in livers was significantly lower in diabetic rats. In liver phospholipids, the differences between the polyunsaturated fatty acid contents of control and diabetic rats in the SAF group, were almost identical to those in erythrocyte lipids. However, in the PER group, a small increase in the 20:4n-6 level, besides an obvious increase in the 18:2n-6 level, was observed in diabetic rats, and n-3 fatty acid levels, especially that of 20:5n-3, were lower significantly in diabetic rats than in control rats. Plasma triglyceride and cholesterol levels in diabetic rats were higher than those in control rats in both dietary groups. The two dietary groups showed significant different triglyceride levels, but similar cholesterol levels. It is suggested that the physiological effect of 18:3n-3 is impaired in diabetes in the same manner as that of 18:2n-6 is. PMID- 8006714 TI - The trophic effects of long chain triglycerides on the atrophic ileal mucosa of rats. AB - Rats with atrophic intestinal mucosa due to enteral nutrition supplied by an elemental diet (ED) for 4 weeks or more, received a fat-enriched ED containing 10% long chain triglycerides (10% FED) orally. The atrophic ileal mucosa became trophic 4 weeks after administration of the 10% FED. Ornithine decarboxylase activity in the ileal mucosa increased 3 days after the administration of 10% FED. Rats with atrophic intestinal mucosa that had undergone a 70% proximal jejunoileectomy, received an oral ED containing 4% long chain triglycerides (4% FED). In the jejunoileectomized rats, marked proliferation of the remaining ileum was observed irrespective of diet, when compared with the transected control group. In the transected group, the 4% FED had trophic effects on the ileum, but in the jejunoileectomized group, the 4% FED had no significant trophic effect on the remaining ileum. In conclusion, long chain triglycerides had mild trophic effects on ileal mucosa and were effective in the treatment of atrophic intestinal mucosa. However, the trophic effects of fat were apparently masked by the marked proliferation of the ileal mucosa following jejunoileectomy. PMID- 8006715 TI - Maltitol-induced increase of transepithelial transport of calcium in rat small intestine. AB - To gain an insight into a mechanism whereby maltitol increases intestinal absorption of calcium, we evaluated transepithelial calcium transport of everted segments of rat small intestine by comparing the values in the presence of maltitol with the values in the presence of maltose. In jejunal segments, no significant difference in the rate of calcium transport was seen between the incubations in the medium containing 100 mM maltitol and in the medium containing 100 mM maltose, regardless of the calcium concentrations in the mucosal-side medium. By contrast, the everted ileal segments incubated in the presence of maltitol exhibited two-fold greater transepithelial calcium transport than did the segments incubated in the presence of maltose at a high (10 mM) concentration of calcium, whereas at a low (0.5 mM) concentration of calcium, maltitol did not produce a significant effect. With the conditions in which intestinal alpha glucosidases were inhibited using the medium containing Tris or acarbose, a slight (40%) but significant increase of calcium transport was again observed in the segments incubated in the medium containing maltitol as compared with the medium containing maltose. The results suggest that maltitol enhances the rate of transepithelial calcium transport in the lower part of small intestine by modulating the passive diffusion of calcium, and that not only the nature of low digestibility, but also some other nature(s) of maltitol might be responsible for the maltitol-induced increase of ileal calcium transport. PMID- 8006716 TI - Estimation of xyloglucan in vegetables by enzyme-linked immunosorbent assay. AB - We prepared the antibody specific against plant xyloglucan and applied it to enzyme-linked immunosorbent assay in order to estimate xyloglucan contents in several vegetables. In this experiment, xyloglucan was detected in the 24% aqueous potassium hydroxide-soluble fractions of tomato, cabbage, lettuce, and eggplant. The xyloglucan contents of these vegetables were estimated to be 1.4 mg, 54 micrograms, 14 micrograms, and 4 micrograms per one hundred grams of their edible portions, respectively, using tamarind xyloglucan as a standard xyloglucan. PMID- 8006717 TI - Inhibitory effect of beta-carotene and astaxanthin on photosensitized oxidation of phospholipid bilayers. AB - Large unilamellar liposomes comprising of egg yolk phosphatidylcholine (PC) was exposed to photoirradiation in the presence of methylene blue (water-soluble photosensitizer) or 12-(1-pyrene)dodecanoic acid (P-12, lipid-soluble photosensitizer) to estimate the inhibitory effect of beta-carotene and astaxanthin on photosensitized oxidation of phospholipid bilayers. Without sensitizers, astaxanthin decreased much slower than beta-carotene and other hydrocarbon carotenoids (lycopene, alpha-carotene). Astaxanthin lasted longer than beta-carotene even in the presence of methylene blue or P-12. Decrease of astaxanthin was also much slower than that of beta-carotene when egg yolk PC was replaced by dimyristoyl PC. However, inhibitory effect of astaxanthin was lower than beta-carotene in the case of P-12 sensitized photooxidation. These results suggest that effectiveness of carotenoids as antioxidants on photosensitized oxidation (Type II) in phospholipid bilayers depends on the site of singlet oxygen to be generated, as well as their stability on photoirradiation. PMID- 8006719 TI - Effects of protein isolates from radish and spinach leaves on serum lipids levels in rats. AB - Radish and spinach leaf protein isolates (RLP and SLP, respectively) were prepared from chilled aqueous 0.2% sodium hydroxide extract of their leaves. The RLP and SLP, and those supplemented with methionine (RLP+Met and SLP+Met, respectively) to become equal to casein in methionine content, were compared with casein for their effects on serum cholesterol level in rats fed with a cholesterol-enriched diet for 14 days. Each protein isolate was incorporated into the cholesterol-enriched diet to provide a 15% protein level. RLP was extremely inferior to SLP and casein for body weight gain of rats, but that of rats fed with RLP+Met diet was almost equal to that of casein and SLP groups. The serum cholesterol level in rats fed with SLP and SLP+Met diets was significantly lower as compared with that of the casein-fed rats. Both the amounts of excreted cholesterol and bile acids were significantly higher in rats fed with the SLP and SLP+Met diets than that of the casein-fed rats. These results suggest that the hypocholesterolemic action of SLP may in part have been due to the inhibition of intestinal absorption of both cholesterol and bile acids. RLP+Met diet tended to decrease the serum cholesterol level as compared to casein diet, but the difference was not significant. PMID- 8006718 TI - Cholestyramine and bile diversion lower the aminopeptidase activity in the intestinal brush border membrane of rats. AB - To examine the effect of bile acids on the activity of intestinal aminopeptidase in vivo, we measured the activity of aminopeptidase in the intestinal mucosa from rats fed the diet containing cholestyramine which sequesters luminal bile acids (experiment 1) and from bile diverted rats (experiment 2). After 32 h fasting, rats were refed for 16 h either of a standard diet (25% casein diets), the same diet containing cholestyramine, or the fat-free diet in experiment 1. In the intestinal washing, the content of total bile acids was markedly decreased with feeding cholestyramine and activities of trypsin and chymotrypsin were also lowered with cholestyramine. Cholestyramine feeding decreased the specific activity of aminopeptidase in the homogenate of intestinal mucosa but increased the specific activities of sucrase and alkaline phosphatase. All these parameters were not modified by the fat-free diet. In experiment 2, bile diverted and sham operated rats were refed the standard diet for 16 h with prior 32 h fasting. Bile diversion, like cholestyramine feeding, lowered the content of total bile acids, the activities of pancreatic hydrolases in the intestinal washings, and the specific activity of aminopeptidase in the intestinal mucosa. The specific activity of sucrase in the intestinal mucosa was higher in bile diverted rats but the activity of alkaline phosphatase was not changed. These data indicate that the decreased abundance of intraluminal bile acid affects the activity of intestinal aminopeptidase not through the decreased absorption of dietary lipid.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8006721 TI - Spectral sharpening: sensor transformations for improved color constancy. AB - We develop sensor transformations, collectively called spectral sharpening, that convert a given set of sensor sensitivity functions into a new set that will improve the performance of any color-constancy algorithm that is based on an independent adjustment of the sensor response channels. Independent adjustment of multiplicative coefficients corresponds to the application of a diagonal-matrix transform (DMT) to the sensor response vector and is a common feature of many theories of color constancy. Land's retinex and von Kries adaptation in particular. We set forth three techniques for spectral sharpening. Sensor-based sharpening focuses on the production of new sensors as linear combinations of the given ones such that each new sensor has its spectral sensitivity concentrated as much as possible within a narrow band of wavelengths. Data-based sharpening, on the other hand, extracts new sensors by optimizing the ability of a DMT to account for a given illumination change by examining the sensor response vectors obtained from a set of surfaces under two different illuminants. Finally in perfect sharpening we demonstrate that, if illumination and surface reflectance are described by two- and three-parameter finite-dimensional models, there exists a unique optimal sharpening transform. All three sharpening methods yield similar results. When sharpened cone sensitivities are used as sensors, a DMT models illumination change extremely well. We present simulation results suggesting that in general nondiagonal transforms can do only marginally better. Our sharpening results correlate well with the psychophysical evidence of spectral sharpening in the human visual system. PMID- 8006720 TI - Influence of galactooligosaccharides on the human fecal microflora. AB - The effects of galactooligosaccharides intake on fecal microflora and their metabolism were investigated in twelve healthy volunteers, in whom the numbers of indigenous bifidobacteria are comparatively low. The galactooligosaccharides ingestion increased the number of bifidobacteria, but remarkable changes of other organisms were not observed. This sugar also lowered fecal nitroreductase activity, the concentrations of indole and isovaleric acid. PMID- 8006722 TI - Two metric solutions to three-dimensional reconstruction for an eye in pure rotations. AB - A problem in space perception concerns how a mobile observer acquires information about the structure of objects. Earlier research derived the optic-flow equations for an eye undergoing pure rotations. It was suggested that, by utilizing three points and two views, one can recover the distance of points and the motion parameters. The radius of the eyeball was the metric unit. Yet the common view regards this problem as indeterminate. We derived a unique solution in the discrete case, which required three points and two views. However, when we observed a single bright point, a substantial amount of visual stability existed. We therefore derived a solution in the differential approach for a single point, which is based on a distinction that we made between mathematical and visual points. Both solutions were checked with a computer simulation and were found to be accurate, supporting the space perception in navigation (SPIN) theory. PMID- 8006723 TI - Perinatal mortality in Oklahoma. AB - OBJECTIVE: To identify areas of need in Oklahoma's perinatal care system by analysis of trends in perinatal mortality from 1939 through 1991. DATA: Derived from birth certificates and annual tabulation published by the Maternal Child Health Division, Oklahoma State Department of Health. RESULTS: Every measure of perinatal mortality has declined in the period studied. CONCLUSIONS: (1) Oklahoma's perinatal mortality rate is declining. (2) Preventable deaths still occur. (3) Programs are in place to appropriately deal with the problems that lead to preventable deaths. (4) These programs must be allowed to continue or expand their efforts to further reduce preventable perinatal death. PMID- 8006724 TI - Pretreatment of viral hepatitis before liver transplantation. PMID- 8006725 TI - Gunshot wounds traversing the mediastinum: guidelines for evaluation and management. AB - When there is suspicion that a penetrating would to the chest has crossed the midline, it is incumbent upon the medical staff to actively exclude injuries to mediastinal structures such as the heart, aortic arch, bronchial tree, and esophagus, even though injury to such structures may not be immediately clinically apparent. The successful management of a patient with a gunshot wound apparently traversing the anterior mediastinum is presented; an esophagram identified an unsuspected through-and-through injury to the esophagus. The evaluation of this patient is discussed, and an algorithm for the evaluation and management of similar patients is proposed. PMID- 8006726 TI - The unspoken chief complaint: family violence. A report from the OSMA Committee on Family Violence. PMID- 8006727 TI - Whores are us. PMID- 8006728 TI - Dealing with information overload. PMID- 8006729 TI - Nerve transposition and implant placement in the atrophic posterior mandibular alveolar ridge. AB - The results obtained with a modified surgical technique for transposition of the inferior alveolar nerve followed by immediate placement of endosseous implants in mandibles with moderate to severe atrophy are presented. Ten transpositions of the inferior alveolar nerve together with the installation of 21 implants were performed in six patients. The mean postoperative follow-up time was 23 months, with a range of 12 to 46 months. All implants with functioning pontics remained stable, with no mobility nor signs or symptoms of pain and infection during the follow-up period. Postoperative radiographic evaluation disclosed no pathologic bone loss around the implants. Neurosensory evaluation was performed using the two-point discrimination test. One patient with unilateral transposition had objective neurosensory dysfunction at 12 months postoperative, although all the nerve function were reported as normal by the patients. Strict patient selection criteria are necessary, with full awareness by the patient of the possibility of long-term or even permanent nerve paresthesia, when this procedure is contemplated. PMID- 8006730 TI - Intraarticular pressure in the functioning human temporomandibular joint and its alteration by uniform elevation of the occlusal plane. AB - Intraarticular pressure (IAP) was measured at the posterior slope of the eminence in the upper compartment of the temporomandibular joint (TMJ) of 35 individuals (28 females and 7 males) under local anesthesia. Pressure measurements were obtained with the jaw in rest position, during maximal mouth opening (MMO), and while clenching. During MMO, IAP decreased to levels ranging between -130 and -5 mm Hg (mean, -53.82 +/- 34.40 mm Hg), whereas during clenching the pressure was always positive (range, +8 to +200 mm Hg; mean, 63.90 +/- 52.25 mm Hg). The significance of the fluctuating pressures with respect to the joint's maintenance and performance, as well as the potentially harmful effect of the positive pressure, especially when it is high and prolonged, are discussed. Females generated significantly higher pressures than males (73.70 +/- 61.06 mm Hg vs 31.42 +/- 11.47 mm Hg, P = .017). This gender difference regarding IAP may help elucidate the enigma of the considerably higher proportion of women with TMJ problems. In 22 of the patients IAP also was measured while clenching on a specifically constructed interocclusal appliance (IOA), which uniformly elevated the occlusal plane so as to reduce the force directed toward the TMJ. During clenching without the IOA, pressures ranged from 20 to 200 mm Hg (mean, 68.8 +/- 49.1), decreasing by 81.2% to IAP levels ranging from 0 to 40 mm Hg (mean, 7.9 +/ 10.9; P < .001) with the appliance in place. The use of an IOA as a palliative treatment for symptomatic TMJs is discussed. PMID- 8006731 TI - Perception of the need for removal of impacted third molars by general dentists and oral and maxillofacial surgeons. AB - This prospective study investigated the influence of professional training and method of payment on how dental practitioners planned extraction of impacted third molars. The subjects were four groups of dental practitioners in metropolitan Chicago: 1) general dentists in traditional fee-for-service practice; 2) general dentists who were members of a preferred provider organization; 3) general dentists who were members of an Independent Practice Association model of a capitation system; and 4) oral and maxillofacial surgeons, all of whom were in fee-for-service practice. A carefully selected and trained professional actress, in good health, with four unerupted, impacted, and asymptomatic third molars, brought her recently taken full mouth periapical and panoramic radiographs to randomly selected dentists for a consultation. The number of planned extractions (no treatment was ever done) was compared. Data showed that oral and maxillofacial surgeons suggested significantly more extractions than capitation dentists and the average of all general dentists, combined. PMID- 8006732 TI - Effect of stimulus force on perioral direction discrimination: clinical implications. AB - Clinicians have used the same instrument (viz, Semmes-Weinstein pressure aesthesiometers [Research Design, Inc, Houston, TX] or "von Frey hairs") for tests of both contact detection and direction discrimination. However, patients' ability to discriminate direction may be underestimated by barely detectable moving stimuli. To determine whether the aesthesiometers underestimate direction discrimination, we evaluated the capacity of 13 normal subjects to distinguish opposing directions provided by 10 different hairs. The hairs were selected to deliver forces below and above the contact-detection threshold. Each was stroked over 1.0 cm of perioral skin at the velocity at which the subject was predicted to best discriminate direction of motion. It was found that valid estimates of perioral direction discrimination can be obtained with appropriately selected aesthesiometers. Specifically, the least stiff hair whose handle displays a manufacturer's marking two units greater than that of the contact-detection "threshold hair" should be used to deliver the moving stimuli. The resultant force applied by this hair will exceed 10 times the subject's contact-detection threshold force. If a less-stiff hair is used, the capacity to distinguish direction may be underestimated. PMID- 8006733 TI - Pexing and presuturing for closure of traumatic soft tissue injuries. AB - The technical values of pexing and presuturing have been confirmed for tumor surgery. Extrapolation of these techniques to the trauma patient has proven worthwhile. This article reviews these methods and presents cases as examples. PMID- 8006734 TI - Esthetic contour analysis of the submental cervical region: a study based on ideal subjects and surgical patients. AB - A cephalometric analysis of the submental-cervical region was carried out by examining and comparing 16 white adults who had ideal submental-cervical esthetics with 16 adult orthognathic surgery patients who were treated by submental lipectomy or liposuction and various orthognathic surgical procedures. A normative data base of the submental-cervical region was derived from the ideal subject group. The submental-cervical morphology of the preoperative patients differed significantly from the ideal subjects. The submental-cervical angle (Sm Ce) and the submental soft tissue thickness at C point (IBM-Sm) presented the greatest disparity between the ideal subjects (118.0 degrees, 28.0 mm) and the preoperative patients (158.3 degrees, 42.1 mm, each P < .001). After surgery, Sm Ce and IBM-Sm decreased to 132.8 degrees (P < .001) and 28.7 mm (P < .001), respectively. By the end of 6 months postoperative, the mean values of Sm-Ce and IBM-Sm were 131.1 degrees and 28.6 mm. The submental soft tissue thickness of the patients 6 months after surgery was not statistically different from the ideal subjects (each P > .05). Orthognathic surgical procedures with concomitant submental lipectomy or liposuction had a significant effect on the contour of the submental and cervical soft tissues. PMID- 8006735 TI - Sagittal ramus osteotomies fixed with biodegradable screws: a preliminary report. AB - Nine patients underwent bilateral sagittal split osteotomies of the mandible. The osteotomies were fixed using two self-reinforced poly-L-lactide screws. No maxillomandibular fixation was used postoperatively. The preliminary results with the shortest follow-up of 15 months show that primary healing was normal. No late term clinical complications were encountered during the follow-up, the longest of which is now 23 months. PMID- 8006736 TI - Long-term evaluation of discectomy of the temporomandibular joint. AB - A clinical and radiographic survey was conducted with 39 patients (39 joints) who had undergone discectomy of the temporomandibular joint between 1965 and 1974 and whose cases had been followed for an average of 20 years after surgery. There were 3 males and 36 females, ranging in age from 16 to 70 years (average, 33 years) at the time of surgery. Masticatory disorders, arthralgia, limitation of condylar movement, and trismus were the chief symptoms, and clicking and crepitus were present in six and two patients, respectively. Plain radiography showed osteoarthritic changes such as osteophyte formation or lipping on the condyles of eight joints. Arthrography showed disc perforations and peridiscal adhesions in 27 patients, and displacement of the disc in eight. All discs were totally extirpated and condylar shaves were performed in eight patients who had disorders such as osteophytes, exostoses, or lipping on the condyles. In follow-up examinations, 37 patients had no pain, but mild arthralgia was noted occasionally in two patients. Postoperatively, no patients experienced subjective masticatory disorders; 38 patients were able to open their mouth more than 35 mm, and crepitus was heard in only two joints. Plain radiography showed bony changes on the condyles and eminences of all joints. From this long-term follow-up study it is concluded that discectomy is a useful operation for treatment of severe disc pathology causing pain and functional disturbance in the temporomandibular joint. PMID- 8006737 TI - Cranial fractures associated with facial fractures: a review of mechanism, type, and severity of injury. AB - A 100-month retrospective review was undertaken to identify the population characteristics of patients with both facial and cranial fractures and to establish the relationships between them. A 4.4% incidence of cranial fractures was found in the 882 patients with facial fractures. These patients tended to be males (85%) between the ages of 16 and 30 years (54%) who were involved in motor vehicle accidents (64%). Patients with midfacial fractures predominated (70%), and these injuries were most frequently associated with fractures of the frontal (38%), sphenoid (24%), or temporal (22%) bones. No relationship was noted between mandibular fractures and cranial fractures. Midfacial fractures were related to individual cranial bone fractures by sutural attachment. The presence of cranial fractures did not play a role in the development of complications associated with facial fractures. PMID- 8006738 TI - Bite forces in patients treated for mandibular angle fractures: implications for fixation recommendations. AB - Voluntary bite forces were recorded at varying periods in 35 males treated with rigid internal fixation for fractures of the mandibular angle. Bite forces were also obtained in 29 male controls for comparison. It was found that molar bite forces in patients were significantly less than in controls for several weeks after surgery. Further, molar bite forces on the side of the fracture were significantly less than on the nonfractured side. The results of this study indicate that recommendations for the amount of fixation required for a given fracture may be reduced. PMID- 8006739 TI - Effects of rigid fixation device composition on three-dimensional computed axial tomography imaging: direct measurements on a pig model. AB - OBJECTIVE: To compare the amount of scatter produced by titanium plates versus Vitallium (Howmedica, Rutherford, NJ) plates. Software was also evaluated to determine its effectiveness in removing the scatter and clarifying the underlying anatomy. MATERIALS AND METHODS: Miniplating and microplating systems composed of Vitallium or titanium were placed on the nasal and frontal bones of three adult pig heads. A computerized axial tomography (CAT) scan was then performed and a three-dimensional CAT scan was reconstructed using MediCad software (MediCad Inc, Cedar Knolls, NJ). The amount of scatter for each plating system was quantitated using the MediCad software measuring tool. The scatter was removed and the three dimensional CAT scan was reconstructed to assess the clarification of the underlying anatomy. RESULTS: No scatter was found with either the miniplating or the microplating system composed of titanium. The Vitallium plates did show significant amount of scatter with the mini, micro, and micromesh system. Removal of the scatter resulted in slight improvement in the anatomic detail. CONCLUSION: Titanium plating systems do not cause any radiation scatter. The MediCad software system allows removal of the scatter found with the Vitallium plates, which helps clarify the underlying anatomy. PMID- 8006740 TI - Biomechanical rationale for surgical-orthodontic expansion of the adult maxilla. AB - OBJECTIVE: To develop a biomechanical rationale for surgical-orthodontic correction of transverse maxillary deficiencies in adults by clarifying the internal stress responses to rapid palatal expansion in a photoelastic model. MATERIALS AND METHODS: A three-dimensional photoelastic analog of an adult human skull was constructed by fabricating the individual facial bones from a photoelastic material and fixing them along their anatomic sutural areas. After determining the force-activation characteristics of a Hyrax expansion appliance in a straining frame, the appliance was applied to the analog and incrementally activated. The stresses developing at the different craniofacial areas were visualized and photographed in the field of a circular polariscope. Sequential cuts were performed to simulate midpalatal, zygomatic buttress, and pterygomaxillary osteotomies, and the alterations in the internal stress responses were recorded after each individual cut. RESULTS: The force-activation characteristics of the Hyrax appliance are in the orthopedic range (500 g). The magnitude and distribution of the stresses induced by appliance activation differed notably between the simulated osteotomies. Analysis of fringe patterns showed that the midpalatal and pterygomaxillary articulations were the primary anatomic sites of resistance to expansion forces. The patterns of distribution and the increase in the magnitude of the stresses at superior sutural location were particularly pronounced after the pterygomaxillary cuts. The forces produced by the Hyrax appliance had deep anatomic effects, with internal stresses also manifesting at regions distant from the site of force application. CONCLUSIONS: Based on photoelastic observation, it may be concluded that complete midpalatal and pterygomaxillary osteotomies are essential for predictable skeletal expansion in adults. Exclusive use of bilateral zygomatic buttress osteotomies appears to be inadequate. The expansion forces exerted by the Hyrax appliance are orthopedic in nature and produce deep anatomic effects. Clinicians should be aware that the craniofacial stresses produced by appliance activation may be experienced by the patient as pain or discomfort. PMID- 8006741 TI - Treatment of mandibular angle fractures: transoral internal wire fixation. PMID- 8006742 TI - Treatment of mandibular angle fractures: plate and screw fixation. PMID- 8006743 TI - Secondarily infected epidermoid cyst in the floor of the mouth causing a life threatening situation: report of a case. PMID- 8006744 TI - Adenosquamous carcinoma of the inferior turbinate: a case report. PMID- 8006745 TI - Intraosseous angiolipoma of the mandible: a case report and review of the literature. PMID- 8006746 TI - Mucous cyst forming on the dorsal surface of the tongue: report of a case. PMID- 8006747 TI - Modified technique for removal of a compressed particulate bone graft from a syringe. PMID- 8006748 TI - Proper fixation of zygomatic arch fractures. PMID- 8006749 TI - Appropriate testing of fixation for the mandibular sagittal split osteotomy. PMID- 8006750 TI - Choosing a pathologist. PMID- 8006751 TI - Sparking from titanium wires. PMID- 8006753 TI - Retirement planning: managing disability risk. PMID- 8006752 TI - A humanitarian tradition. PMID- 8006754 TI - Melting the myths of peer review. PMID- 8006756 TI - Recognizing the signs of child abuse--the Kansas dentist responsibility. PMID- 8006755 TI - Is it a profession or a business? PMID- 8006757 TI - Chemical dependency and the dental patient. PMID- 8006758 TI - Joint annual meeting of the American Society of Tropical Medicine and Hygiene and The American Society of Parasitologists. Atlanta, Georgia, October 31-November 4, 1993. Abstracts. PMID- 8006759 TI - Sustained-release dosage form of nitrofurantoin. Part 1. Preparation of microcapsules and in vitro release kinetics. AB - A new sustained-release dosage form of nitrofurantoin as microcapsules was prepared by carboxymethylcellulose-aluminium sulphate simple coacervation technique. In vitro release studies for microcapsules and their formulated hard gelatin capsule and tablet forms were performed. Release rates were studied as functions of core: wall ratios and the particle sizes of the microcapsules. Dissolution tests of microcapsules and their dosage forms were studied in simulated gastric and intestinal media without enzyme using the USP XXI basket method. Release data were examined kinetically and the ideal kinetic models were estimated for drug release. In addition, optical and electron scanning microscopic works were carried out on the microcapsules. PMID- 8006760 TI - Sustained-release dosage form of nitrofurantoin. Part 2. In vivo urinary excretion in man. AB - The in vivo absorption of crystalline nitrofurantoin and the dosage forms of nitrofurantoin prepared with microcapsules were carried out in man by determination of urinary excretion of unchanged nitrofurantoin. The cumulative amount of drug excreted and the duration of the therapeutic urine levels were compared. The microcapsule administration showed that the peak reached during the excretion of nitrofurantoin in urine, decreased significantly when compared to the pure drug. This could be an explanation for the decrease in side-effects of nitrofurantoin such as nausea and vomiting. Experiments in male albino rats showed that the microcapsules did not produce gastric haemorrhage seen with the same doses of the pure drug. PMID- 8006761 TI - Magnetically responsive diclofenac sodium-loaded erythrocytes: preparation and in vitro characterization. AB - Diclofenac sodium-bearing magnetic erythrocytes were prepared using a preswell technique. The optimum loading of drug and magnetite achieved were 63-73 and 12 18 per cent, respectively. Drug-loaded erythrocytes and drug-loaded magnetic erythrocytes were characterized for in vitro drug and haemoglobin release, magnetic responsiveness, osmotic fragility, turbulence shock, morphology and percentage cell recovery. The drug-loaded magnetic erythrocytes were found less resistant to osmotic and turbulence shock when compared with the normal and drug loaded erythrocytes. However, in optimum concentration erythrocytes tolerated drug and coated magnetite appreciably. The drug-loaded magnetic erythrocytes responded effectively for an external magnetic field of 8.0 kOe. The study suggested the potentiality of diclofenac sodium-loaded magnetic erythrocytes, for active delivery of drug to painful inflamed joints. PMID- 8006762 TI - Formulation, preparation and dissolution characteristics of propranolol hydrochloride microspheres. AB - Propranolol HCl was encapsulated with cellulose acetate butyrate (CAB) by an emulsion-solvent evaporation method to obtain discrete, spherical microspheres. The effects of drug to polymer ratio and microsphere size on dissolution characteristics were studied. Drug release was faster in simulated intestinal fluid than in simulated gastric fluid. Unencapsulated propranolol HCl powder had very rapid dissolution, as expected. Release rate from CAB microspheres increased with higher drug to polymer ratios and decreased with increasing diameter. Drug release from microspheres sizes larger than 180 microns was reasonably well described by the spherical matrix model. For microsphere size fractions between 127 and 359 microns the relationship between the 50 per cent release time and the square of the microsphere diameter was linear (r = 0.9999). PMID- 8006763 TI - Effect of compression pressure on physical properties and dissolution characteristics of disintegrating tablets of propranolol microspheres. AB - Propranolol HCl was encapsulated with cellulose acetate butyrate by an emulsion solvent evaporation method. Three direct compression diluents were blended with appropriate size fractions of the microspheres and each formulation was compressed at several pressures to give tablets that readily disintegrated in water. Tablets with microcrystalline cellulose (MC) as the diluent had the highest tablet crushing strength at any given compression pressure. Heckel plots of all the microsphere-diluent blends were nonlinear, indicating that the consolidation may result from crushing and rearrangement of the individual particles in addition to plastic deformation. Tablet properties and estimated yield pressures showed that MC was the most suitable diluent for compression of propranolol HCl microspheres. Drug release from compressed tablets was always faster than from uncompressed microspheres, but useful sustained-release characteristics were retained. Dissolution tests of MC formulations of the tableted microspheres showed increased release rate constants and decreased 50 per cent dissolution times compared to microspheres that had not been compressed. This result indicated that rupture of some of the microspheres had occurred. The drug release rate increased at higher compression pressures due to the rupture of a greater proportion of microspheres. Larger changes in release rate and t50 percent were observed with larger microspheres sizes. Generally, the least compression pressure that gives tablets with acceptable properties is preferred. PMID- 8006764 TI - Preparation of polyamide microcapsules having narrow size distributions. AB - A novel emulsification technique which employs microporous glass membranes was adopted to prepare polyamide microcapsules of narrow size distribution. This technique proved to be simple and quite efficient for getting fairly uniform sizes of dispersed liquid droplets. Polyamide microcapsules prepared by using this technique were found not completely monodisperse, but far more satisfactory than those by any conventional mechanical methods in view of their narrow size distribution. This method also seems promising to get various sizes of the capsules by selecting the pore size of the glass membranes. PMID- 8006765 TI - Characterization and tissue distribution of liposomes containing lactose mono fatty acid derivatives. AB - In this study we characterized liposomes containing the synthetic glycolipids, lactose mono-fatty acid esters (LFEs), whose structures were the most simple ones compared to the other synthetic glycolipids. Gel filtration chromatography was used to confirm that 78 per cent of lactose monostearic acid ester (LSE) or 85 per cent of lactose monoarachidic acid ester (LAE) existed in the liposomal fraction. The size distribution of liposomes containing LFEs was similar to that of the control liposomes which did not contain LFEs. Liposomes containing LFEs were aggregated by Ricinus communis agglutinin from caster bean (RCA120) while the control liposomes were not, with the agglutinability of the liposomes containing LAE being greater than that of those containing LSE. These findings therefore suggested that the LFEs were incorporated into the liposomal membrane with the galactose residues exposed to the outer aqueous phase. Next, the tissue distribution of liposomes containing LAE at 30 min after intravenous administration was compared to that of the control liposomes in rats. Hepatic uptake was 2-fold higher than that of the control liposomes. These results thus demonstrate that liposomes containing LFEs represent potential drug carriers to the liver. PMID- 8006766 TI - Microencapsulation of Lactococcus lactis subsp. cremoris. AB - Lactococcus lactis subsp. cremoris was microencapsulated within alginate/poly-L lysine (alg/PLL), nylon or crosslinked polyethyleneimine (PEI) membranes. Toxic effects were observed with solvents and reagents used in nylon and PEI membrane formation. Alg/PLL encapsulation resulted in viable and active cell preparations which acidified milk at a rate proportional to the cell concentration, but at rates less than that of free cell preparations. At 4 x 10(8) colony-forming units (cfu/ml milk), encapsulated cells took 17 per cent longer than free lactococci to reduce the pH of milk to 5.5. Similar activities of free and micro-encapsulated cells may be attained at higher cell concentrations (10(9) cfu/ml milk). The rate of lactic acid production was approximately 2 mmol/h at an encapsulated cell concentration of 4 x 10(8) cfu/ml. PMID- 8006767 TI - Microencapsulation with carrageenan-locust bean gum mixture in a multiphase emulsification technique for sustained drug release. AB - A multiphase emulsification technique was modified in this process of micro encapsulating gentamicin sulphate, thus avoiding the necessity for a surfactant in preparing the secondary emulsion for a W/O/W emulsion. Various proportions of iota-carrageenan (i-C) and locus bean gum (LBG) were investigated for the W/O/W emulsion after forming the primary W/O emulsion with sorbitan trioleate, Span 85. Upon removal of the oil phase (chloroform) from the W/O/W emulsion by heating (60 65 degrees C), microcapsules or 'W/W' particles containing drug dissolved in sodium hyaluronate were spontaneously formed. These were dispersed in a solution of a mixture of 5-10 per cent w/v polyvinyl alcohol, PVA (average MW 50,000 106,000; 98 per cent hydrolysed) and 3 per cent v/v polyethylene glycol 200 (PEG 200), and dried to form the hydrogel film casts. Our in vitro experiments in isotonic phosphate buffer solution (pH 7.4) at 37 degrees C, showed that the release of gentamicin sulphate was dependent on concentration of LBG, and concentration or molecular weight of PVA. With the exception of PVA hydrogel matrix preparations containing 20 per cent w/v LBG, all other formulations showed a significant initial 'burst' release of drug within 6 h. The drug-containing microcapsules in the PVA hydrogel film with 20 per cent w/v LBG, exhibited an almost zero-order release of drug up to 140 h. It is postulated that an effective barrier or high-density membrane enveloping the microcapsules was formed between i-C and LBG because of their unique molecular configurations. This phenomenon, together with the possible adsorption of i-C molecules at the transient oil and outer aqueous phase interface, presumably eliminated the need for a permanent oil phase and/or an O/W surfactant normally required for preparing W/O/W emulsions. PMID- 8006768 TI - Polyhydroxamic microcapsules prepared from proteins: a novel type of chelating microcapsules. AB - Microcapsules were prepared from three proteins, namely human serum albumin (HSA), bovine fibrinogen and ovalbumin, by an interfacial crosslinking process using terephthaloylchloride. They were further treated with alkaline hydroxylamine in order to disrupt ester and anhydride bonds in the walls. All microcapsules survived the treatment. They exhibited a significant increase in size and became sensitive to trypsin. The hydroxylamine treatment also resulted in attachment of hydroxamic groups to the membrane, making the microcapsules capable of iron binding. These properties were evaluated after soaking microcapsules in a 140 mumol/l ferric solution and determination of iron in the supernantant. Lower amounts of iron were found to be complexed by HSA microcapsules (mean value: 29.3 mumol iron/g microcapsule dry weight) as compared with fibrinogen and ovalbumin microcapsules (43.7 and 44.9 mumol/g, respectively). Microcapsule chelating properties were further improved by esterification of the free carboxyl groups of the membrane with benzyl alcohol or ethanol using a carbodiimide, prior to the hydroxylamine treatment. Comparable values of iron binding were obtained from esterified and hydroxylamine-treated batches prepared from the three proteins (about 50 mumol iron/g). PMID- 8006769 TI - Recent advances in the Doppler study of early fetomaternal circulation. AB - Transvaginal color Doppler has enabled precise investigation of feto-maternal circulation in early pregnancy. Decrease of peripheral impedance, as well as increase of blood flow velocity was found in all segments of the uteroplacental circulation with gestational age. The same finding was observed in umbilical artery, fetal aorta and intracranial blood vessels. A significant decrease of vascular impedance in cerebral blood vessels exists earlier than in fetal aorta or umbilical artery which could be explained by the establishment of cerebral autoregulation mechanisms which ensure adequate oxygen and glucose supply to embryonic brain. There was no significant difference for RI values of luteal blood flow from the 6th to the 12th gestational week. No difference was found between RI values of luteal blood flow in normal and ectopic pregnancy. In threatened, incomplete and missed abortions RI of luteal blood flow was significantly higher in comparison with normal pregnancy. It seems that in the group of patients with threatened abortion, follow up of the luteal flow might give some prognostic value. No difference in peripheral impedance and blood flow velocity of the uteroplacental blood vessels was found between women with normal pregnancies and women with threatened abortions and normal pregnancy outcome. There was no significant difference in terms of RI and PSV in uteroplacental blood vessels between women with threatened abortion and normal pregnancy outcome and women with threatened abortion whose pregnancy terminated with complete abortion and blighted ovum. In 46% of 21 women with visible retrochorionic hematoma RI in spiral arteries was higher and PSV was lower on the side of the hematoma. These values could be explained by compression of the wall of the spiral arteries caused by hematoma. In missed abortion the mean RI value of the uterine artery was lower than the mean value in normal pregnancy, but was not in spiral arteries. Some authors reported RI values in cases of missed abortions around and above the cutoff point value of 0.63. In blighted ovum RI in uterine and spiral arteries was lower in comparison to normal pregnancy, but in the other studies this was not the case. Increased blood flow in radial arteries in patients with pregnancy associated with uterine myomata could be explained by higher levels of estriol hormone metabolized in the placenta. Transvaginal color Doppler could be helpful in diagnosis and differentiation of the different forms of a gestational trophoblastic disease. It seems that this technique is a good substitute for pelvic angiography.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8006770 TI - New approaches to the prediction of preterm delivery. AB - Current approaches to the detection of patients at risk for preterm delivery (PTD) have focused on the diagnosis of preterm labor. However, these approaches are complicated by treatment biases and our inability to convincingly differentiate preterm labor from Braxton-Hicks contractions. Moreover, preterm labor with intact membranes accounts for only one-half of all spontaneous PTDs since uterine contractions follow preterm premature rupture of the membranes (PROM) in an additional 50% of cases. Clinical dogma holds that the prevention of PTD requires the early detection of at risk patients. However, clinical indicators of PTD risk including cervical change, uterine contractions, vaginal bleeding, maternal demographic featuers and obstetrical history have poor sensitivity and/or specificity. Fortunately, an improved understanding of the association between preterm parturition and cervical, chorionic and decidual extracellular matrix degradation has led to a number of promising new biochemical indices of the proteolytic processes leading to PTD. These include measurement of serum collagenase activity and assessment of cervico-vaginal granulocyte elastase and oncofetal fibronectin levels. It remains to be seen, however, whether an improved detection of patients at risk will lead to a reduction in the occurrence of PTD. PMID- 8006771 TI - Angiogenesis: a new diagnostic aspect of obstetric and gynecologic echography. AB - An ultrasounds triplex system (pulsed Doppler, Color mode, B mode) has been employed to study ovarian and uterine circulatory changes in fertile, infertile and postmenopausal patients. PI and mean percentage variation of PI mean values have been used. No difference has been detected in uterine haemodynamics between fertile women and those infertile patients getting pregnant by IVF-ET procedure. Patients who did not obtain the pregnancy showed different uterine and endometrial Color Doppler patterns. Furthermore, a typical endometrial blood flow has been detected both in fertile patients and infertile patients who get pregnant. Color Doppler seems to be an useful tool in the monitoring of fibroids blood supply and the uterine blood supply, especially for the clinical monitoring of GnRH analogues therapies. The technique has been also employed for the study of ectopic pregnancy. The evaluation of both uterine and throphoblast haemodynamics has resulted in a good indicator of the pregnancy progression. Concerning the ovarian pathology the color Doppler evaluation has been useful to differentiate ovarian malignant cysts from inflammatory or disfunctional masses. Nevertheless, the most interesting results have been obtained from the study of endometrial and ovarian tumors. Indeed, in the most cases, a mass supply blood flow has been detected, although in some cases no angiogenetic color flow has been found. No difference has been found in uterine artery velocimetry between malign or benign pathologies. Furthermore, histological data supporting our findings are presented. PMID- 8006772 TI - Fetal monitoring by pulse oximetry and CTG. AB - To see if a pulse oximeter can monitor the fetus during labour we recruited 100 Caucasian women in normal uncomplicated labour. Our primary objective was to compare the predictive value of fetal pulse oximetry and cardiotocography using neonatal condition and cord blood acidaemia or hypoxaemia at birth as outcome variables. The fetuses were monitored continuously with a pulse oximeter specifically adapted for fetal use. Five babies had an operative delivery because of an abnormal CTG. Two of these were born in good condition (Apgar score 9 at 1 minute in both cases). The other three babies were delivered in poor condition (Apgar scores of 6 & 9, 5 & 10 and 5 & 10 at 1 and 5 minutes respectively). The oxygen saturation reading only dropped significantly in babies born in poor condition and in one case the drop preempted the CTG changes. These data suggest that pulse oximetry can be adapted to monitor the fetus and has the potential to provide useful information during labour. PMID- 8006773 TI - Plasma prostacyclin and thromboxane concentrations in 160 normotensive, hypotensive, and preeclamptic patients during pregnancy, delivery, and the post partum period. AB - Plasma concentrations of 6-keto-prostaglandin F1 alpha, a stable metabolite of prostacyclin, and TxB2 were measured in 160 women during pregnancy (n = 106), delivery (n = 40), and in the postpartum period (n = 14). Fifty nine patients had normal blood pressure, 10 had mild and 9 severe preeclampsia while 38 patients were hypotensive. Normotensive patients were grouped according to their gestational age: 22-26 weeks (n = 22), 27-31 weeks (n = 22), and 32-38 weeks (n = 15). 20 patients were in early first stage of delivery (cervical dilatation < or = 5 cm), 20 patients in late first stage (cervical dilatation > or = 6 cm). The concentration (mean value +/- SEM) of the PGI2 metabolite tended to increase during pregnancy without reaching significance (218 +/- 11; 225 +/- 10; 250 +/- 15 pg/ml). At the same time, TxB2 showed a decrease, which was most pronounced at 27-31 weeks (65 +/- 15; 40 +/- 2; 48 +/- 4 pg/ml; p < 0.001). The ratio of PGI2/TxA2 increased in parallel (4.9 +/- 0.4; 6 +/- 0.4; 4 +/- 0.5). There was no difference in plasma concentrations of PGI2 (figure 4) and TxA2 in patients with normal blood pressure, mild preeclampsia and hypotension, whereas in severe preeclampsia, the plasma concentration of PGI2 was significantly lower (p < 0.001) and of TxA2 significantly higher (p < 0.001). The ratio of PGI2/TxA2 shifted significantly to vasoconstriction in patients with severe preeclampsia (p < 0.0001) and to vasodilatation in those with hypotension (p < 0.03).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8006774 TI - Collagen of umbilical cord arteries and its alterations in EPH-gestosis. AB - We decided to investigate the EPH-gestosis--connected alterations in collagen of the umbilical cord arteries. The samples of arterial walls were submitted to histological and biochemical studies. It was found that umbilical cord arteries taken from newborns of mothers with EPH-gestosis contain more than twice the amount of collagen in comparison to corresponding arteries of newborns from normal pregnancies. An increase of collagen content in these vessels in accompanied by a slight decrease of its solubility. Types I, III, IV, V and VI collagens were found both in normal umbilical cord arteries and in those of newborns delivered by mothers with EPH-gestosis but their proportional relationships were different. EPH-gestosis is accompanied by an increase of a proportional amount of type III-collagen and a decrease of type I collagen in umbilical cord arteries. It seems that these changes in the umbilical cord arteries may be responsible for the decrease of blood flow in fetus of woman with EPH-gestosis. PMID- 8006775 TI - Intrapartum fetal heart rate responses to maternal exercise. Case reports. AB - Intrapartum fetal heart responses to a maternal exercise routine are described in two volunteers. The fetal heart rates were not affected by a brief exercise, which intensity was approximately 60% of the maximum aerobic capacity. These patients reported decreased pain perception during the exercise in labor. PMID- 8006776 TI - Long-term care--can the church meet the challenge of reform? PMID- 8006777 TI - When sugarplums go sour--will health care reform help the poor? PMID- 8006779 TI - Melanie Kernekin's commitment to life. Interview by Marcia Banks. PMID- 8006778 TI - Ethical impotence--when choice and Christian values conflict. PMID- 8006781 TI - Dusting off the pledge. PMID- 8006782 TI - Throwing stones--choosing to care for PWA. PMID- 8006780 TI - Pro-Life nurses uniting for service. PMID- 8006783 TI - Beyond the diagnosis--caring for a cancer patient. PMID- 8006784 TI - Faith and politics: strange bedfellows? PMID- 8006785 TI - Soul on fire. PMID- 8006786 TI - A call to action: influencing health care reform. PMID- 8006787 TI - Keratorefractive surgery with the excimer laser. PMID- 8006788 TI - Ultrasound biomicroscopic assessment of the cornea following excimer laser photokeratectomy. AB - Excimer laser photokeratectomy is used as a refractive tool and in the treatment of superficial corneal disease. Ultrasound biomicroscopy is a new method of ultrasound imaging developed in our laboratories that allows subsurface imaging of ocular structures at microscopic resolution. We used this imaging method to examine 12 patients following excimer laser keratoablation. Following treatment, the normal appearance of a highly reflective Bowman's membrane below the epithelial echo was absent in the treatment zone. Corneal thinning was also noted. Postoperative scarring in the treatment area could be imaged as highly reflective regions in the superficial stroma. In therapeutic cases, corneal opacities could be imaged pretreatment and their depth assessed. The degree of opacity removal could be analyzed post-treatment. Ultrasound biomicroscopy helped assess corneal changes secondary to excimer laser photokeratectomy. PMID- 8006789 TI - Effect of postoperative steroids on the refractive outcome of photorefractive keratectomy for myopia with the Summit excimer laser. AB - To assess the role of topical steroids following excimer laser photorefractive keratectomy (PRK) for myopia, we compared the refractive outcome in 100 eyes that did not receive steroids in the immediate postoperative period (untreated eyes) with 100 eyes that were treated with topical dexamethasone for three months postoperatively. Photorefractive keratectomy was performed with the Summit laser, using 4.3 mm and 4.5 mm ablation zones. At three months after surgery, the untreated eyes had a mean refraction of -0.97 +/- 1.15 diopters (D), significantly different (P < .01) from the mean refraction (+0.46 +/- 0.74 D) of the steroid-treated eyes. By six months postoperatively, 86% of the untreated eyes had regressed to a myopia of at least 0.50 D, whereas only 23% of the steroid-treated eyes had regressed. In a second study, we compared the results in 25 patients whose first PRK eye was treated with steroids after surgery but whose second eye was not. At three months postoperatively, mean refraction in the steroid-treated eyes was +1.23 +/- 0.71 D, significantly different (P < .01) from the mean of -0.45 +/- 1.29 D in the untreated eyes. The refractive results in PRK eyes treated with the Summit unit and with relatively small ablation zone diameters showed that eyes that received dexamethasone postoperatively were less likely to regress to myopia. PMID- 8006790 TI - Use of topical nonsteroidal anti-inflammatory drugs in excimer laser photorefractive keratectomy. AB - Nonsteroidal anti-inflammatory drugs (NSAIDs) produce potent analgesic, antipyretic, and anti-inflammatory effects. We studied postoperative pain in 97 consecutive patients having photorefractive keratectomy (PRK) by an excimer laser with different topical NSAID protocols. Treatment with topical homatropine hydrobromide, either diclofenac sodium (Voltaren Ophthalmic) or ketorolac tromethamine (Acular), and a soft contact lens was most effective in achieving post-PRK analgesia. We also studied post-PRK myopic regression in 68 consecutive patients and found that flurbiprofen sodium (Ocufen), when added to topical steroid protocols, significantly reduced myopic regression for one year postoperatively more than steroids alone or steroids and diclofenac sodium. Diclofenac, used with topical steroids, had less of an additive effect on myopic regression than did flurbiprofen. Topical NSAIDs are useful adjuncts to PRK therapy, both to eliminate postoperative pain and to control post-PRK myopic regression. PMID- 8006791 TI - Results of photorefractive keratectomy on 63 myopic eyes with six months minimum follow-up. AB - We present our experience with 63 myopic eyes that had photorefractive keratectomy with an excimer laser. Minimum follow-up was six months. Mean preoperative myopia was -3.98 diopters (D) (range: -9.00 D to 1.25 D) and mean preoperative uncorrected visual acuity, 20/220. The epithelium was removed and fixation accomplished with a suction ring. Photoablation was then performed on a 5.0 mm diameter optical zone. Mean postoperative myopia was -0.60 D (range: -6.35 D to +2.25 D) after six months. Mean uncorrected visual acuity was 20/30. All corneas had a subepithelial haze that decreased progressively. There were no major complications. Except in a few cases, predictability was satisfactory. Photorefractive keratectomy proved effective throughout the trial. We need to study more patients with a longer follow-up to determine the indications and applications of this technique. PMID- 8006792 TI - Excimer laser photorefractive keratectomy for myopia: two-year follow-up. AB - We evaluated the results of photorefractive keratectomy (PRK) with an excimer laser on 45 consecutive myopic eyes (23 patients) that were followed two years or more. The myopic range was from -2.00 diopters (D) to -6.00 D with astigmatism less than 1.50 D. Uncorrected visual acuity better than 20/25 was achieved in 88.9% of all cases two years postoperatively. Best corrected visual acuity was equal to or better than preoperatively in 95.6% of eyes. The difference between the attempted and achieved correction was within +/- 1.00 D in 91.1% two years postoperatively. Keratometric readings and central corneal thickness showed a gradual restoration until six months postoperatively and then stabilized. The cornea was clear in 66.7% of the eyes. The most common subjective complaint was decreased night vision two years after PRK. From our experience, excimer laser PRK is a predictable and effective surgical method to correct myopia up to -6.00 D in a single-step procedure. PMID- 8006793 TI - Photorefractive keratectomy to treat low, medium, and high myopia: a multicenter study. AB - This prospective, multicenter study investigated what influence patient age, sex, and time to re-epithelialization after myopic photorefractive keratectomy (PRK) have on stability of achieved correction and intensity of corneal haze. Seven surgeons performed PRK to correct myopia on 325 eyes using the same operative procedure, type of laser, and post-PRK treatment. Follow-up was from six to 12 months. Results indicate that corneal haze intensity is influenced by the time to re-epithelialization of the treated corneal surface. Patient age and sex may also affect haze intensity, although the results from this study were not conclusive. PMID- 8006795 TI - Excimer laser correction of myopic astigmatism. AB - The excimer laser allows the controlled ablation of corneal tissue to correct refractive error. By using a combination of spherical and slit apertures, it is possible to correct both myopia and astigmatism. We report the results of 139 consecutive eyes that had photoastigmatic refractive keratectomy (PARK) for myopic astigmatism (myopia < or = -15.00 diopters [D] with astigmatism < or = 6.00 D) and compare these results with 107 consecutive and concurrent eyes that received photorefractive keratectomy (PRK) for myopia (< or = -15.00 D). The same excimer laser was used by 27 different surgeons. All patients were followed for at least three months. In the PARK group, 68% were within +/- 1.00 D at six months and 77% were within +/- 2.00 D. In the PARK group, these figures were 87% and 97%, respectively. Uncorrected visual acuity of 20/40 or better was achieved in 72% of PARK and 90% of PRK patients at six months. Minor adverse reactions occurred in 6% of PARK and 11% of PRK patients. No significant surgeon effect was seen. Photoastigmatic refractive keratectomy provides a realistic approach to the surgical correction of myopic astigmatism and is comparable to PRK in safety and efficacy. PMID- 8006794 TI - Use of the 193 nm excimer laser for photorefractive keratectomy in low to moderate myopia. AB - As part of a Phase III clinical trial, photorefractive keratectomy using the VISX 2015 193 nm excimer laser was performed on 91 sighted eyes of 91 patients. Preoperative refractive errors (spherical equivalent) ranged from -1.00 diopters (D) to -7.50 D (mean -4.11 D +/- 1.43 D). At six months, average residual refractive error was 0.02 D +/- 0.64 D (range -2.21 D to +1.38 D). Ninety-three percent of eyes were within 1.00 D of attempted correction, 93% had uncorrected visual acuity of 20/40 or better, and 72% achieved uncorrected visual acuity of 20/25 or better. All patients returned to their best corrected visual acuity within one line of their preoperative best corrected visual acuity. Photorefractive keratectomy with the 193 nm excimer laser appears to be useful in reducing low to moderate myopia. PMID- 8006796 TI - Photorefractive keratectomy to correct astigmatism with myopia or hyperopia. AB - Excimer laser photorefractive keratectomy as a means to flatten the central cornea has generated considerable interest. With this technique radial symmetric ablations can be performed to correct myopic refractive errors and excise superficial corneal pathology. We developed a technique that uses toric ablation to correct astigmatism. A new mask was designed for the MEL 60 Aesculap-Meditec excimer laser. The mask can be rotated regularly over 360 degrees. By varying the angular distances, the surgeon can increase ablation depth in any desired meridian. As a result, both cylindrical and spherical errors can be corrected in one procedure. Seventy-three eyes with either simple, myopic, mixed, or irregular astigmatism were treated. In each category of astigmatism, the surgery reduced the spherical component as well as the overall mean preoperative cylindrical refraction. Our findings suggest that this technique is a safe and effective procedure for correcting different types of astigmatism. PMID- 8006797 TI - Treatment of myopic astigmatism with the 193 nm excimer laser utilizing aperture elements. AB - In this paper, we examine the 193 nm excimer laser's efficacy and safety in treating myopic astigmatism. The VISX Twenty/Twenty excimer laser uses aperture elements to effect astigmatic photorefractive keratectomy. In 70 patients with six months follow-up, the average postoperative sphere was -0.14 and the average postoperative cylinder was -0.54. Seventy-one percent of these patients had uncorrected visual acuity of 20/40 or better at six months. In 12 patients with one year follow-up, the average postoperative sphere was -0.05 and the average postoperative cylinder was -0.59. Eighty-three percent of these patients had uncorrected acuities of 20/40 or better; none had a clinically significant loss of best corrected acuity. This investigation demonstrates that the excimer laser can be used to treat myopic astigmatism successfully. PMID- 8006798 TI - Photorefractive keratectomy for myopic astigmatism: phase IIA of the Federal Drug Administration study (12 to 18 months follow-up). Excimer Laser Study Group. AB - Excimer laser photorefractive keratectomy was performed on eight eyes to investigate toric ablation of naturally occurring compound myopic astigmatism. Follow-up ranged from 12 to 18 months. In each surgical case, the spherical component was reduced. The cylindrical component was reduced or eliminated in seven of eight eyes and remained unchanged in one eye. However, six of eight eyes had some residual astigmatism and three had 0.75 diopters of cylinder or more. In six of eight eyes the change in axis in the postoperative cylinder varied between 5 and 10 degrees of the preoperative cylinder axis. In one eye with an eccentric ablation, the axis changed by 40 degrees. In two eyes with loss of best corrected visual acuity of one line each, from 20/20 to 20/25, irregular astigmatism and subepithelial haze persisted 18 months after treatment. One eye gained a line of best corrected visual acuity from 20/20 to 20/15. Two eyes were overcorrected. Twenty-five percent of patients achieved 20/20 or better uncorrected visual acuity, 62.5% achieved 20/40 or better uncorrected acuity, and 100% achieved 20/50 or better uncorrected acuity. These preliminary results of excimer laser photoastigmatic keratectomy compare favorably with reports of photorefractive keratectomy for myopia alone. There were no adverse reactions to treatment. The procedure was effective although some residual astigmatism was found in most patients. PMID- 8006799 TI - Phacoemulsification with intraocular lens implantation after excimer photorefractive keratectomy: a case report. AB - We report the first case, to our knowledge, of phacoemulsification with lens implantation in a patient with previous photorefractive keratectomy for myopia. Intraocular lens calculations were performed using manual and automated keratometry. The surgical and postoperative course were uneventful with a good visual outcome. Standard intraocular lens calculation and surgical technique appear to be successful for cataract extraction after photorefractive keratectomy. PMID- 8006800 TI - Ongoing results of excimer laser photorefractive keratectomy for myopia: subjective patient impressions. AB - We present the results of a survey carried out by independent researchers to determine the subjective success rate of a series of excimer laser photorefractive keratectomy procedures to correct myopia. Thirty patients, selected at random from a group of 300, had received treatment to both eyes with a minimum of six months follow-up on the second eye. Forty-four patients, selected at random from a group of 120, had received treatment to one eye only with five months of follow-up. The results show a high level of satisfaction with the results of the procedure. PMID- 8006801 TI - Management of urinary tract infections in pregnancy. AB - Urinary tract infections (UTIs) are one of the most frequent complications of pregnancy. When the lower UTIs of asymptomatic bacteriuria and cystitis are not eradicated, the subsequent risk of the development of pyelonephritis is increased. The associated decreased maternal morbidity and fetal prematurity are the goals of a screening and treatment program for pregnant women. This clinical article presents information on the etiology, incidence, diagnosis, and management of asymptomatic bacteriuria and cystitis. Nursing implications regarding teaching are included. PMID- 8006802 TI - A multidisciplinary approach to the management of pregnant patients with end stage renal disease. AB - End-stage renal disease (ESRD) in pregnancy is a complex perinatal condition requiring a multidisciplinary approach to care. This article will summarize the literature, provide a brief overview of dialysis therapy, describe the inherent maternal and fetal complications, and present a case history of a pregnant patient with ESRD. The clinical management, using a multidisciplinary approach, is discussed in detail, with a major focus on the obstetric nursing plan of care. PMID- 8006803 TI - Pyelonephritis in pregnancy. AB - Pyelonephritis, while rare in nonpregnant women, is the leading cause of hospitalization for nonobstetric indications in pregnant women. Pregnancy complications such as preterm labor and intrauterine growth retardation have been associated with pyelonephritis. Pyelonephritis can also lead to life-threatening conditions such as endotoxic shock and respiratory insufficiency. Thus the condition requires hospitalization and close follow-up in the pregnant women. PMID- 8006804 TI - Pregnancy following renal transplant. AB - Pregnant patients who have experienced a renal transplant require specialized obstetric management and nursing interventions. Patient care must be developed in a multidisciplinary approach that addresses the needs of the pregnancy as well as the allograft status. Medications to protect the allograft from rejection present unique concerns in the clinical care management of pregnant women. This article describes the collaborative patient care that brings these areas together and reviews nursing interventions and therapies appropriate for the patient who experiences a pregnancy following renal transplant. PMID- 8006805 TI - Renal function in the neonate. AB - Renal function is altered in the neonate in comparison to the adult. Although structurally complete in terms of numbers of nephrons by 36 weeks, the newborn kidney is still functionally immature. Renal function undergoes rapid maturation during the first weeks postbirth in both term and preterm infants. During this time there is little margin for error in regulation of fluid and electrolyte balance, especially for the very low-birth-weight infant. Significant risks for all infants include overhydration, dehydration, and electrolyte imbalances. This article describes development of the renal system, anatomic and physiologic characteristics in the neonate, and implications for practice. PMID- 8006806 TI - Antifungal agents and their renal implications in the neonate. AB - The incidence of superficial or systemic fungal infections has been increasing in neonates. The cause of this increased susceptibility to fungal infections is due to the increased use of mechanical ventilation, indwelling catheters, broad spectrum antibiotic therapy, parenteral nutrition, and steroid therapy. The most common organism encountered in neonatal infections is Candida species. This article will cover the etiology, signs, symptoms, diagnosis, and treatment of the usual neonatal fungal infections. Each of the antifungal agents used to treat neonates will be discussed with regard to its mechanism of action, pharmacokinetics, indications, normal and renal functional impairment dosing, and adverse effects. PMID- 8006807 TI - Ethical issues in the neonatal patient with end-stage renal disease. AB - While treatment for the neonate continues to be challenging, current technical advances offer more options. Before the 1980s chronic dialysis was technically so difficult for neonates and infants that most considered it impossible; in the 1990s renal replacement therapy is a viable choice. The purpose of this article is neither to advocate active intervention nor passive supportive care, but to help the reader consider questions frequently faced when deciding what to do for a neonate with end-stage renal disease (ESRD). Today ethical issues are tied closely to health care reform, so this bioethical dilemma has only begun. As health care reform addresses benefits of care, the bioethical dilemmas raised by neonates with ESRD will need to carefully considered. PMID- 8006808 TI - Adrenaline-regulated Cl- transport in cultured single rat epididymal cells measured by an entrapped Cl-(-)sensitive fluorophore. AB - 1. Isolated cells from primary cultures of rat epididymal epithelial cells were employed for the study of adrenaline-stimulated Cl- transport using a Cl-( )sensitive fluorophore 6-methoxy-N-(3-sulphopropyl) quinolinium (SPQ). SPQ was loaded into the cells by the hypotonic shock method. 2. The resting intracellular Cl- concentration, estimated in the presence of nigericin and tributyltin in high K+ solution, was 62.3 +/- 0.2 mM. This value was not altered in the presence of 1 microM adrenaline. When extracellular Cl- was replaced by NO3-, an increase in fluorescence corresponding to a decrease in intracellular Cl- was observed. The initial outward Cl- movement was estimated to be 0.54 +/- 0.08 mM s-1. This value was increased by incubating the cells with adrenaline. The stimulatory effect of adrenaline was reduced by 1 mM DPC. 3. Addition of Cl- to cells previously depleted of Cl- caused an instantaneous decrease in fluorescence due to the entry of Cl-. The initial rate of Cl- entry was -0.62 +/- 0.13 mM s-1. Adrenaline increased the rate of entry to -2.13 +/- 0.08 mM s-1. The adrenaline-stimulated rate of entry was reduced by DPC or frusemide (0.5 mM) and was completely blocked in the presence of both agents. 4. In Na(+)-free solution, the adrenaline stimulated rise of rate of Cl- entry was reduced in the presence of DPC. Frusemide had no effect on the entry rate. 5. The stimulatory effect of adrenaline were abolished by propranolol (5 microM) but not by phentolamine (5 microM). Conversely, isoprenaline (1 microM) and forskolin (1 microM) mimicked the effects of adrenaline.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8006809 TI - Activity-dependent regulation of inwardly rectifying potassium currents in non myelinating Schwann cells in mice. AB - 1. Voltage-gated potassium currents were recorded from freshly dissociated non myelinating Schwann cells of sural and sympathetic nerves from 1- to 12-week-old mice using the whole-cell or a single channel variation of the patch-clamp technique. 2. All sural cells from 2-week-old mice showed inwardly rectifying potassium (Kir+) currents in whole-cell recordings. Kir+ currents were virtually undetectable in sural cells from mice more than 6 weeks old, which also showed depolarization of the resting membrane potential. On the other hand, the magnitude of Kir+ currents increased in cervical sympathetic trunk (CST) cells in parallel with an increase of cell capacitance 1-6 weeks after birth. The density of Kir+ currents in CST cells increased 1-4 weeks after birth and then stayed constant for up to 12 weeks. 3. The unitary conductance of a single Kir+ channel in CST cells was 30 pS 2-12 weeks after birth; this was recorded in a cell attached configuration with 154 mM K+ in the pipette. The steady-state open channel probability of single Kir+ channels in CST cells decreased with membrane hyperpolarization, but was not markedly changed 2-12 weeks after birth. 4. Conduction block of CST for 5 days induced by local application of tetrodotoxin (TTX) resulted in a significant decrease in both the magnitude and the density of Kir+ currents in whole-cell recordings in CST cells rostral to the sites of TTX block. Similar changes of Kir+ currents in whole-cell recordings were observed in cells in the inferior postganglionic branch of a superior cervical ganglion after 5 days of TTX block of CST. 5. These results suggest that neuronal activity regulates the expression of functional Kir+ channels in non-myelinating Schwann cells in adult nerves. The activity-dependent regulation of the expression of glial potassium channels could play an important role in the regulation of the potassium microenvironment around active axons to maintain impulse conduction in unmyelinated fibres. PMID- 8006810 TI - Properties of afferent nerve fibres supplying the saphenous vein in the cat. AB - 1. We examined the responses of primary afferent neurones supplying a vascularly isolated segment of the saphenous vein to mechanical and chemical stimuli in anaesthetized cats. Activity was recorded from centrally cut axons of afferent nerve fibres which were isolated from the saphenous nerve near its junction with the femoral nerve. 2. A total of thirty units responded to one of these stimuli and twenty-three of them were activated by local mechanical stimulation of the venous wall. Most receptive fields were circular spots. The response of the isolated venous segment to distension was tested in fifteen out of thirty units and eight out of fifteen were activated. Intravasal threshold pressures inducing discharges were in the range of 35-250 mmHg with a mean of 120 mmHg. 3. Twenty seven out of the thirty units were tested for both mechano- and chemosensitivity. Thirteen were classified as A fibres and fourteen as C fibres with conduction velocities of 5-30 m s-1 and less than 2.5 m s-1 respectively. Twenty fibres (12/13 A, 8/14 C) were mechanosensitive. Two-thirds of the mechanosensitive A (8/12) and all of the mechanosensitive C fibres (8/8) responded to at least one of the chemical stimuli used: hypertonic saline, bradykinin (BK) or capsaicin. 4. The remaining seven units (6 C, 1 A) were activated by injection of BK into the isolated venous segment but failed to respond to mechanical stimuli. Six were found during five experiments in which BK was used as a search stimulus. Injection of bradykinin into the isolated venous segment repeatedly induced an increase in systemic blood pressure. 5. The proportion of unmyelinated fibres responding to mechanical stimulation of the venous segment was systematically examined in three experiments and amounted to about 1% of the unmyelinated afferents in the saphenous nerve. 6. In conclusion, a small proportion of afferent nerve fibres in the saphenous nerve responds to presumably noxious mechanical and/or chemical stimuli applied to the saphenous vein. These fibres, together with some chemospecific venous afferents, may be capable of encoding nociceptive information from the vein especially under pathological conditions. PMID- 8006811 TI - Topographical organization of the cerebellar cortical projection to nucleus interpositus anterior in the cat. AB - 1. A new methodological approach for detailed study of the organization of the cerebellar corticonuclear projection was evaluated in barbiturate-anaesthetized cats. Extracellular field potentials were simultaneously recorded in nucleus interpositus anterior and in the forelimb area of the C3 zone, at the cerebellar surface. On electrical and natural stimulation of the forelimb skin, the evoked positive field potentials in the nucleus and the climbing fibre field potentials in the cerebellar cortex had similar characteristics, indicating that the nuclear potentials were related to climbing fibre activity. 2. Application of a local anaesthetic to the cerebellar surface reversibly diminished the positive field potentials in the nucleus, demonstrating that the potentials were dependent on cerebellar cortical activity. It was thus concluded that the positive field potentials were mainly generated by climbing fibre-activated Purkinje cells and reflected synaptic inhibitory potentials in nuclear neurones. Accordingly, the positive field potentials in the nucleus could be used to reveal the termination area of Purkinje cells activated by a specific climbing fibre input evoked on peripheral stimulation. 3. The topographical organization of the cerebellar cortical projection to the forelimb part of nucleus interpositus anterior was then investigated by systematically mapping the cutaneous tactile and nociceptive 'receptive fields' of the positive field potentials at different sites in the nucleus. Five groups of receptive fields were distinguished and tentatively divided into a total of nineteen subgroups. 4. Each group of receptive fields corresponded to one or two of the previously described receptive field classes of climbing fibres to the C1, C3 and Y zones and was represented in a single area of the nucleus. Within each area there was an orderly representation of different receptive fields. The results suggest that microzones in the C1, C3 and Y zones with similar climbing fibre input project to a common set of neurones in nucleus interpositus anterior. 5. We propose a modular organization for the cerebellar control of forelimb movements through the rubrospinal tract. Each module would consist of a set of neurones in nucleus interpositus anterior and their afferent microzones in the C1, C3 and Y zones. A module would control a specific group of muscles and receive a homogeneous climbing fibre input related to the movement controlled. PMID- 8006812 TI - Effect of tonic voluntary activity on the excitability of human motor cortex. AB - 1. The threshold for obtaining EMG responses after transcranial magnetic stimulation of the brain is reduced by voluntary contraction of the target muscle. The present experiments tested whether some of this effect is due to increased cortical, as opposed to spinal, excitability during the contraction. 2. Magnetic stimulation was delivered with a figure-of-eight coil oriented with the junction region along the interaural line and also (in 4 of 7 subjects) with a circular coil centred at the vertex. The intensity of the conditioning stimulus was subthreshold for evoking a motor response in the relaxed wrist flexor muscles of the forearm. The presence of a small descending corticospinal volley in both the relaxed and active conditions was detected by measuring the facilitation of test H reflexes elicited in the flexor muscles of the forearm. 3. In all subjects, magnetic stimulation with either coil facilitated the H reflex at conditioning-test intervals of -1 to -3 ms (median nerve stimulus before magnetic). This was followed by a long-lasting facilitation. In three of the seven subjects stimulation with the figure-of-eight coil elicited an additional, earlier peak of facilitation at a conditioning-test interval of -3 to -5 ms. 4. In all subjects, the threshold for obtaining facilitation of the H reflex using a conditioning-test interval of -1 to -3 ms was reduced, and the amount of facilitation was larger, if subjects performed a weak tonic voluntary contraction. In contrast, with a conditioning-test interval of -3 to -5 ms voluntary contraction had no effect on the threshold. 5. It is suggested that H reflex facilitation at the conditioning-test interval of -1 to -3 ms was produced by indirect activation of corticospinal neurones by the magnetic stimulus, whereas at -3 to -5 ms, the facilitation was produced by direct activation of corticospinal axons. It is concluded that tonic voluntary contraction of a target muscle decreases the threshold for indirect activation of corticospinal neurones but not for direct stimulation of their axons. PMID- 8006813 TI - Inactivating 'ball' peptide from Shaker B blocks Ca(2+)-activated but not ATP dependent K+ channels of rat skeletal muscle. AB - 1. Shaker B inactivating 'ball' peptide is shown to produce no detectable block of ATP-dependent K+ channels of rat skeletal muscle fibres at concentrations up to 300 microM or membrane potentials up to +30 mV. 2. The peptide does produce a voltage-dependent block of large-conductance Ca(2+)-activated K+ channels at lower concentrations (K1 = 55 microM at 0 mV). An appropriate point mutation (L7E) abolishes block. 3. Mean open times, corrected for missed closures, are little affected by the blocking peptide, but burst durations are substantially reduced. 4. The inactivating peptide increases occupancy of substates, whose amplitudes are 0.27 and 0.64 of fully open. PMID- 8006814 TI - Evidence for the non-existence of a negative phase in the hump charge movement component (I gamma) in Rana temporaria. AB - 1. Charge movement was studied in cut twitch fibres of Rana temporaria with a double Vaseline-gap voltage-clamp technique. 2. When charge movement was measured from stretched fibres (3.5 microns sarcomere length) bathed in a TEA-Cl Ringer solution, the ON transients in the appropriate potential range showed an early I beta component followed by an I gamma hump. The late I gamma hump generally decayed monotonically towards the maintained current level. 3. On some rare occasions, the ON transient showed an undershoot immediately following the I gamma hump before reaching the steady-state level. This dip in current, when it occurred, could only be observed in a very narrow potential range and might not persist until the end of the experiment. 4. A replacement of the Cl- in the external solution by CH3SO3- reduced the magnitude of the dip, suggesting that the dip is ionic in origin. 5. When charge movement was measured in slack fibres (2.2 microns sarcomere length, the probability of observing the dip in current was increased. 6. In some experiments in which the dip in current was very stable, the signal was studied by a sequence of TEST pulses to the same potential but with different durations. It was found that, if the dip in current was included as a negative phase of the I gamma hump, then the amount of ON charge was smaller than that of OFF charge. Also, as the pulse duration was increased progressively so that a longer portion of the dip was recorded, the OFF charge remained constant instead of being decreased.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8006815 TI - Contractile activation and force generation in skinned rabbit muscle fibres: effects of hydrostatic pressure. AB - 1. Effects of hydrostatic pressure (range 0.1-10 MPa) on the isometric tension of skinned (rabbit psoas) muscle fibres were examined at 12 degrees C and at different levels of Ca2+ activation (pCa range 4-7); the effects on both the steady tension and the tension transients induced by rapid pressure release (< 1 ms) are described. 2. The steady tension was depressed by increased pressure (approximately 1% MPa-1) at a high level of Ca2+ activation (pCa approximately 4) whereas it was potentiated at lower Ca2+ levels (pCa > 6); the effects were reversible. 3. At maximal Ca2+ activation, the tension recovery following pressure release (10 MPa to atmospheric) consisted of a fast (approximately 30 s 1) and a slow (2-3 s-1) phase; the rate and the normalized amplitude (normalized to the steady tension at atmospheric pressure for a particular pCa) of the fast phase were invariant with changes in Ca2+ level. 4. The effects of changing Ca2+ level on the slow phase were complex; its positive amplitude at high Ca2+ levels changed to negative and the rate decreased to approximately 1 s-1 at low Ca2+ levels (pCa > 6.0). 5. Results are discussed in relation to previous studies on the effect of pressure on intact muscle fibres and the actin-myosin interaction. This work supports calcium regulation of cross-bridge recruitment rather than calcium regulation of the rate of a specific step in the cross-bridge cycle. PMID- 8006816 TI - The role of sarcoplasmic reticulum in relaxation of mouse muscle; effects of 2,5 di(tert-butyl)-1,4-benzohydroquinone. AB - 1. Intracellular calcium concentration ([Ca2+]i) and force were measured from isolated single mouse skeletal muscle fibres at rest and during tetani. The actions of 2,5-di(tert-butyl)-1,4-benzohydroquinone (TBQ), an inhibitor of the sarcoplasmic reticulum (SR) Ca2+ pump, were examined at a range of concentrations (100-1000 nM). 2. TBQ increased resting [Ca2+]i, increased tetanic [Ca2+]i and slowed the rate of decline of [Ca2+]i after a tetanus. TBQ produced a small increase in tetanic force and a large slowing of the rate of relaxation after a tetanus. All these effects were reversible. 3. TBQ had no important effects on the Ca2+ sensitivity or the maximum force produced by the myofibrillar proteins. 4. Analysis of the SR Ca2+ pump function confirmed that under control conditions and at very low levels of [Ca2+]i, the relationship between [Ca2+]i and SR pump rate was a 4th power function. TBQ caused a pronounced inhibition of the pump rate and reduced the power function to < 3. 5. Muscle fibres were fatigued by repeated tetani until tetanic [Ca2+]i and force were reduced and the rate of decline of [Ca2+]i after a tetanus was slowed. Under these conditions application of TBQ caused a further slowing of the rate of decline of [Ca2+]i but still increased tetanic [Ca2+]i and force. This result suggests that slowing of the SR pump rate is not the cause of the decline in tetanic [Ca2+]i and force at the late stage of fatigue. 6. A simple model of the interactions of Ca2+, TBQ and pump proteins is described, which predicts the 4th power function of the normal pump, inhibition by TBQ, and the reduced power function in the presence of TBQ. 7. A model of Ca2+ movements and force development in muscle is described, which closely matches the experimental results under control conditions. Inhibition of the SR pump by TBQ using the model of the pump described above simulates qualitatively all the observed effects of TBQ on [Ca2+]i and force. 8. In conclusion, TBQ is a potent, specific and reversible inhibitor of the SR Ca2+ pump in intact mouse skeletal muscle. Inhibition of the pump directly affects intracellular Ca2+ handling and force production. PMID- 8006818 TI - Coupling between variations in strength and baroreflex latency of sympathetic discharges in human muscle nerves. AB - 1. Pulse-synchronous multiunit muscle nerve sympathetic activity was recorded simultaneously from two nerves together with ECG in eleven healthy subjects; seven recordings were made from the two peroneal nerves during prolonged expiratory apnoeas and four from a radial and a peroneal nerve during lower body negative pressure of 10-40 mmHg. The neural records were displayed in mean voltage neurograms (time constant 0.1 s) and for each mean voltage burst the following measures were taken and related to each other: amplitude, duration, rise time, decay time and baroreflex latency (from the appropriate R-wave of the ECG to the peak of the burst). 2. Average baroreflex latencies were 1.3 s in the peroneal nerves and 0.9 s in the radial nerve. There were significant positive correlations between both the amplitudes and the baroreflex latencies of corresponding bursts in peroneal-peroneal recordings and in radial-peroneal recordings. 3. In all nerves baroreflex latency shortened significantly when burst amplitude increased. The correlation between burst amplitude and baroreflex latency was weaker in the radial than in the peroneal nerve. The average variation of baroreflex latency in peroneal-peroneal recordings was 0.20 +/- 0.02 s in both legs, and in radial-peroneal recordings the variation was 0.09 +/- 0.01 s in the radial nerve and 0.12 +/- 0.02 s in the peroneal nerve. 4. When peroneal burst amplitudes increased, burst duration increased. This was due to increases of both the rise time and the decay time of the burst, the latter being the greater.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8006817 TI - Myofibrillar ATPase activity and mechanical performance of skinned fibres from rabbit psoas muscle. AB - 1. The relationship between energy turnover and mechanical performance was investigated in chemically skinned single fibres from rabbit psoas muscle at 15 degrees C, pH = 7.1, with MgATP, 5 mM; free Mg2+, 1 mM; ionic strength, 200 mM and sarcomere length, 2.4 microns by measuring force production and myofibrillar ATP turnover during isometric contractions as well as during repetitive changes in length. ATP hydrolysis was stoichiometrically coupled to the breakdown of NADH, which was measured photometrically via the absorption of near UV light at 340 nm. 2. Force and ATPase activity were measured during square-wave length changes of different amplitudes (1-10% of the fibre length, Lo) and different frequencies (2.5-167 Hz). The average force during the length changes was less than the isometric value and decreased with increasing amplitude and frequency. At full activation (pCa 4.5), the isometric ATP turnover rate (+/- S.E.M.) was 2.30 +/- 0.05 s-1 per myosin head. ATP turnover increased monotonically with increasing amplitude as well as with increasing frequency until saturation was reached. The greatest increase observed was 2.4 times the isometric value. 3. Force and ATPase activity were also determined for ramp shortenings followed by fast restretches. The average force decreased with increasing shortening velocity in a hyperbolic fashion. The ATP turnover increased with ramp velocity up to 0.5 L0 s-1 and stayed almost constant (at 2.2 times the isometric value) for larger velocities. 4. Isometric force and ATPase activity both decreased as the calcium concentration was decreased. They did not vary in proportion at low Ca2+ concentrations, but this could largely be accounted for by the presence of a residual, Ca(2+)-dependent, membrane-bound ATPase. At high calcium concentrations ATPase activity during square-wave length changes was higher than the isometric value, but at low calcium concentrations (pCa > 6.1), the ATPase activity during the length changes decreased below the isometric value and reached a minimum of 40% of the isometric level. 5. ATPase activity and average force obtained during changes in length show a high, movement protocol-independent correlation. During the length changes the rate of ATP turnover divided by the average force level (tension cost) was larger than the isometric tension cost. The largest value found, for 10% length changes at 23 Hz, was 17 times the tension cost under isometric conditions.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8006819 TI - Stretch reflex responses in the human elbow joint during a voluntary movement. AB - 1. The responsiveness of the stretch reflex is modulated during human voluntary limb movements. The influence of this modulation on the limb mechanical properties (stiffness) was investigated. 2. Subjects were taught to replicate accurately a rapid (4.0 rad s-1) targeted elbow flexion movement of 1 rad. From the onset of 12% of the trials a sinusoidal position disturbance (0.05 rad) was superimposed on the normal (trained) movement trajectory. The net joint torque (muscle torque) resisting these stretches was computed from measurements of applied torque, acceleration and limb inertia. Electromyographic (EMG) responses in the triceps brachii (TB), brachialis (Br) and biceps brachii (BB) were monitored. 3. The EMG responses to sinusoidal stretches applied early in the movement were less than those responses to perturbations applied when the arm neared the target (especially in the antagonist muscle TB). These EMG responses caused fluctuations in the resistance to the perturbation (stiffness), as described below. 4. When the perturbation frequency was low (< 4 Hz) the resistance of the elbow muscles to the stretch increased as the arm approached the target (48% increase). In contrast, when the stretch frequency was 7 Hz the resistance decreased by 63%. This decrease can be explained by the increased reflex response, since at 7 Hz the reflex response is probably timed so that it assists, rather than resists, the stretching as a result of loop delays. This reflex timing was confirmed by observing that, after abruptly stopping the sinusoidal stretch, the reflex response persisted for 100 ms and was indeed in a direction that would have reduced the resistance, had the perturbation continued. 5. The time course of the net muscle stiffness was estimated for frequencies ranging from 4 to 8 Hz and for each 40 ms interval a Nyquist plot was constructed, forming a C-shaped curve as frequency was varied. The size of this curve gave a measure of the stiffness resulting from reflex activity. When the arm neared the target this reflexive stiffness reached a maximum, and was probably comparable in size to the intrinsic (non-reflexive) muscle stiffness. Also, in four of the five subjects the viscous component of stiffness at 7 Hz dropped significantly below zero when the arm neared the target, again indicating that at this frequency the reflex was large and acted inappropriately.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8006820 TI - Active forearm blood flow adjustments to handgrip exercise in young and older healthy men. AB - 1. Our purpose was to test the hypothesis that ageing impairs the active muscle hyperaemia consequent to dynamic exercise in humans. 2. Eleven young (19-29 years) and eleven older (60-74 years) healthy, non-obese men with similar chronic physical activity levels and forearm size performed two protocols of dynamic handgrip exercise: (a) brief (1 min), incremental loads to exhaustion, and (b) sustained (8 min), submaximal loads. Active forearm blood flow (FBF) was measured at rest and during a brief period of relaxation at the end of each minute of exercise. Arterial blood pressure was recorded to calculate active forearm vascular conductance (FVC). Sustained forearm ischaemia plus handgrip was used to elicit a peak forearm vasodilatatory response. 3. There were no differences in pre-exercise levels of any variable between the young and older men. During exercise, ratings of perceived effort, the peak workload attained, and the ability to sustain submaximal workloads were all similar for the two groups. 4. During brief exercise, both submaximal and peak levels of FBF were similar in the two groups; however, the peak increases in FVC were greater in the older men. During sustained exercise, FBF and FVC were not different in the two groups at the lowest loads, but the increases became relatively greater in the older men with increasing workloads. 5. Peak levels of FBF and FVC in response to the peak vasodilatatory stimulus were similar in the young and older men. 6. These findings fail to support the postulate that ageing results in impaired active muscle hyperaemia and vasodilatation during small-muscle dynamic exercise.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8006821 TI - Pyloric motility and liquid gastric emptying during barostatic control of gastric pressure in pigs. AB - 1. In conscious pigs, intragastric pressure was controlled by a water barostat such that the gastroduodenal pressure gradient was always positive with the barostat set above 15 cm. In six pigs pyloric motor function was removed by prior pylorectomy. 2. In pylorus-intact animals, isolated pyloric pressure waves (IPPWs) occurred at a median of 2.9 min-1 during duodenal dextrose infusion with the barostat set at or above a threshold of 15 cm. Increases of intragastric pressure above this threshold had no additional effect upon rates of IPPWs. Below this threshold, with identical duodenal dextrose infusion, IPPWs occurred infrequently (0.5 min-1). In pylorus-excised animals virtually no IPPWs were seen. 3. In both pylorus-intact and -excised animals, the rate of antral pressure waves (APWs) was dependent upon intragastric pressure during duodenal infusion of both saline and dextrose. No threshold for stimulation was seen. Duodenal dextrose infusion inhibited APWs in pylorus-intact animals only. 4. With a positive gastroduodenal pressure gradient, gastric emptying was more rapid in pylorus-excised animals than pylorus-intact animals during duodenal dextrose infusion. In contrast, gastric emptying rates were not different between pylorus intact and -excised animals during saline infusion. 5. These findings suggest an all-or-none-type stimulation of localized pyloric contractions by distension of the stomach beyond a threshold, in synergism with stimulation by nutrients within the upper small bowel. In contrast, stimulation of antral motility is in proportion to distension of the stomach. The pylorus, by way of localized pyloric contractions, is an effective resistor to transpyloric flow in the face of a positive gastroduodenal pressure gradient. PMID- 8006822 TI - pH dependence of inositol 1,4,5-trisphosphate-induced Ca2+ release in permeabilized smooth muscle cells of the guinea-pig. AB - 1. The dependence on pH of inositol 1,4,5-trisphosphate (IP3)-induced Ca2+ release was studied in saponin-skinned smooth muscle cells from guinea-pig portal vein, using the indicator fura-2 to monitor Ca2+ release. 2. Increasing pH between 6.7 and 7.3 enhanced the rate of IP3-induced Ca2+ release at all the Ca2+ concentrations above 30 nM without changing the bell-shaped dependence of the Ca2+ release rate on Ca2+ concentration with a peak near 300 nM. 3. The ascending limb of the biphasic Ca2+ dependence was shifted slightly toward the lower Ca2+ concentration at pH 7.3, suggesting an increase in the Ca2+ sensitivity of IP3 induced Ca2+ release at the higher pH. 4. With the elevation in pH from 6.7 to 7.3 at 100 nM Ca2+, about 7-fold higher IP3 concentration was required to release half of the Ca2+ in the store within 15 s. This pH-dependent change in the IP3 sensitivity was smaller at 1 microM Ca2+ and was indiscernible in the absence of Ca2+. 5. These results suggest that H+ may inhibit binding of IP3 and Ca2+ to the modulator sites of the Ca2+ release mechanism. However, these effects on the binding sites may not fully explain the complex effect of pH, and there may be pH dependent step(s) involved in the gating mechanism of IP3 channels. The present study demonstrates the importance of pH as a modulator of IP3-induced Ca2+ release. PMID- 8006823 TI - Outwardly rectifying chloride current in rabbit osteoclasts is activated by hyposmotic stimulation. AB - 1. We characterized chloride currents in freshly isolated rabbit osteoclasts using whole-cell and single channel patch-clamp recording configurations. Depolarization activated an outwardly rectifying current in 40-50% of cells, distinct from the inwardly rectifying K+ current we have previously reported in osteoclasts. 2. The outwardly rectifying current persisted under conditions where all K+ currents were blocked. Furthermore, the outward current was reversibly inhibited by Cl- transport blockers 4-acetamido-4'-isothiocyanostilbene-2,2' disulphonic acid (SITS); 4,4'-diisothiocyanostilbene-2,2'-disulphonic acid (DIDS); 4,4'-dinitrostilbene-2,2'-disulphonic acid (DNDS); and niflumic acid. The blocked current had a reversal potential close to the predicted chloride equilibrium potential and was dependent on the chloride concentration gradient. 3. In those osteoclasts in which outwardly rectifying current was not initially apparent, exposure to hyposmotic extracellular solution resulted in its reversible activation. The induced current was due to Cl-, based on its reversal close to the chloride equilibrium potential and sensitivity to blockade by Cl- channel inhibitors. The hyposmotically induced current could be activated in Ca(2+)-free solutions containing 0.2 mM EGTA. 4. When studied in the current clamp configuration, hyposmotic stimulation caused depolarization from -76 +/- 5 to -5 +/- 6 mV (mean +/- S.D., n = 7). 5. Unitary Cl- currents were recorded in the cell-attached patch configuration at positive potentials. Single channels had a slope conductance of 19 +/- 3 pS (n = 5). Reduction of the external [Cl-] shifted the current-voltage relationship in the positive direction, supporting the conclusion that these were Cl- currents. Like the whole-cell currents, single channel Cl- currents were activated by exposure of cells to hyposmotic bathing solution. 6. We conclude that rabbit osteoclasts express an outwardly rectifying Cl- current that can be activated by osmotic stress. Cl- channels may play a role in cell volume regulation and may also provide conductive pathways for dissipating the potential difference that arises from electrogenic proton transport during bone resorption. PMID- 8006824 TI - Calcium-dependent chloride current induced by axotomy in rat sympathetic neurons. AB - 1. Seven to ten days after sectioning their axons, rat sympathetic neurons were studied using intracellular recording techniques in an in vitro preparation of the superior cervical ganglion. 2. In 75% of axotomized cells, an after depolarization (ADP) was observed following spike firing or depolarization with intracellular current pulses. Discontinuous single-electrode voltage-clamp techniques were employed to study the ADP. When the membrane potential was clamped at the resting level just after an action potential, a slow inward current was recorded in cells that showed an ADP. 3. In the presence of TTX and TEA, inward peaks and outward currents were recorded during depolarizing voltage jumps, followed by slowly decaying inward tail currents accompanied by large increases in membrane conductance. The inward peak and tail currents activated between -10 and -20 mV and reached maximum amplitudes around 0 mV. With depolarizing jumps to between +40 and +50 mV, net outward currents were recorded during the depolarizing jumps but inward tail currents were still activated. 4. In the presence of the Ca2+ channel blocker cadmium, or when Ca2+ was substituted by Mg2+, the ADP disappeared. In voltage-clamped cells, cadmium blocked the inward tail currents. The reversal potential for the inward tail current was approximately -15 mV. Substitution of the extracellular NaCl by sucrose or sodium isethionate increased the amplitude of the inward tail current, and displaced its equilibrium potential to more positive values. Changes in extracellular [K+] did not appreciably affect the inward tail current amplitude or equilibrium potential. Niflumic acid, a blocker of chloride channels activated by Ca2+, almost completely blocked the tail current. 5. No ADPs were observed in non axotomized neurons, and when depolarizing pulses were applied while in voltage clamp no inward tail currents were evoked in these normal cells. 6. It is concluded that axotomy of sympathetic ganglion cells produces the appearance of a Ca(2+)-dependent chloride current responsible for the ADP observed following spike firing. PMID- 8006825 TI - K+ and Cl- transport mechanisms in bovine pigment epithelium that could modulate subretinal space volume and composition. AB - 1. Conventional and ion-selective double-barrelled microelectrodes were used in an in vitro bovine retinal pigment epithelium (RPE)-choroid preparation to measure the changes in membrane voltage, resistance and intracellular K+ and Cl- activities produced by small, physiological changes in extracellular potassium ([K+]o). 2. In the intact eye, light-induced changes in [K+]o occur in the extracellular (or subretinal) space that separates the neural retina and the RPE apical membrane. These [K+]o changes can be approximated in vitro by decreasing apical bath [K+]o from 5 to 2 mM. 3. This in vitro change in [K+]o simultaneously decreased intracellular Cl- and K+ activities (aCli and aKi) by 25 +/- 6 mM (n = 8) and 19 +/- 7 mM (n = 4) (mean +/- S.D.), respectively. In control Ringer solution (5 mM [K+]o) aCli and aKi were 65 +/- 10 mM (n = 28) and 65 +/- 8 mM (n = 6), respectively. 4. The [K+]o-induced decreases in aCli and aKi were both significantly inhibited, either by blocking the apical membrane K+ conductance with Ba2+ or the basolateral membrane Cl- conductance with DIDS (4,4' diisothiocyano-stilbene-2,2'-disulphonic acid). 5. Transepithelial current pulses were used to determine the relative basolateral membrane Cl- conductance, TClBAS, was approximately 0.6 (n = 3), and the relative apical membrane K+ conductance, TKAP, was approximately 0.7 (n = 2). Step changes in basal bath [K+]o were used to estimate the relative basolateral membrane K+ conductance, TKBAS, was approximately 0.34 (n = 3). 6. These data show that the apical membrane K+ conductance and the basolateral membrane Cl- conductance are electrically coupled. In vivo, this coupling could have significant functional importance by modulating the relative hydration of the subretinal space, regulating RPE cell volume, and buffering the chemical composition of the subretinal space. PMID- 8006826 TI - GABAergic and glutamatergic synaptic input to identified granule cells in salamander olfactory bulb. AB - 1. Whole-cell patch clamp recording techniques were applied to granule cells in an in vitro salamander olfactory bulb preparation to study their morphology, membrane properties and pharmacology of postsynaptic responses to electrical stimulation of either the olfactory nerve (ON) or medial olfactory tract (MOT). Optical recordings of the same preparations stained with the voltage-sensitive dye RH414 were also made. 2. Anatomical reconstructions of biocytin-filled granule cells showed that they extend widespread spine-bearing dendrites and an axon-like process that branched within the external plexiform layer. 3. ON or MOT stimulation evoked a long-lasting depolarization, usually generating only a single action potential, in granule cells studied under standard recording conditions. Bath application of bicuculline methiodide (BMI, a GABAA receptor antagonist, 20 or 25 microM) enhanced the spontaneous and electrically evoked excitatory drive to granule cells. 4. The electrically evoked synaptic responses consisted of both excitatory and inhibitory synaptic inputs. Using symmetrical Cl conditions inside and outside the cell to enhance Cl- currents, spontaneous and electrically driven BMI-sensitive inhibitory postsynaptic currents (IPSCs) were revealed, indicating that granule cells receive GABAergic synaptic input. 5. Bath application of GABA (250 microM to 1 mM) shunted and hyperpolarized granule cells as observed directly from whole-cell recordings and indirectly from cell-attached patch single channel recordings. 6. Bath application of the glutamate receptor antagonists 6-cyano-2,3-dihydroxy-7-nitroquinoxaline (CNQX, 10 microM) and/or DL 2-amino-5-phosphonopentanoic acid (DL-AP5, 100 microM) showed that granule cell dendrodendritic EPSPs are shaped by both non-NMDA and NMDA receptors. 7. The time course and pharmacological sensitivity of both single granule cell responses and ensemble responses recorded optically in the deeper layers of the bulb correlated well. 8. It is concluded that salamander granule cells integrate several types of synaptic input, may have both dendritic and axonal output, and play a major role in generating voltage-sensitive dye signals in the olfactory bulb. PMID- 8006827 TI - Modulation of AMPA/kainate receptors in cultured murine hippocampal neurones by protein kinase C. AB - 1. The patch clamp technique, together with intracellular perfusion of the catalytic fragment of protein kinase C (PKCM), was employed to investigate the role of this enzyme in the intracellular regulation of alpha-amino-3-hydroxy-5 methyl-4-isoxazole propionate (AMPA)/kainate receptors in cultured hippocampal neurones. 2. The responses evoked by near-maximal concentrations of kainate (250 microM) and AMPA (100 microM) were potentiated by the introduction of PKCM, whilst co-application of the inhibitory peptide fragment PKCI(19-36) prevented this action. 3. Modulation of kainate responses by PKCM was dependent upon the concentration of agonist applied. Currents evoked by kainate were potentiated at concentrations above those which caused 50% of the maximal response (EC50) and depressed at lower concentrations. Furthermore, okadaic acid, a specific inhibitor of phosphatases 1 and 2A, had a similar effect upon concentration response relationships when currents activated by kainate were recorded using the perforated patch technique. 4. In addition, the mean amplitude and/or time constant of decay of miniature excitatory synaptic currents (mediated by AMPA/kainate receptors) was increased by the intracellular injection of PKCM. 5. These observations suggest that the function of postsynaptic excitatory amino acid receptors can be modulated by the activity of PKC as well as by endogenous phosphatases. This regulation may contribute to some forms of synaptic plasticity within the central nervous system. PMID- 8006828 TI - Interneurones in pathways from group II muscle afferents in sacral segments of the feline spinal cord. AB - 1. Properties of dorsal horn interneurones that process information from group II muscle afferents in the sacral segments of the spinal cord have been investigated in the cat using both intracellular and extracellular recording. 2. The interneurones were excited by group II muscle afferents and cutaneous afferents but not by group I muscle afferents. They were most effectively excited by group II afferents of the posterior biceps, semitendinosus, triceps surae and quadriceps muscle nerves and by cutaneous afferents running in the cutaneous femoris, pudendal and sural nerves. The earliest synaptic actions were evoked monosynaptically and were very tightly locked to the stimuli. 3. EPSPs evoked monosynaptically by group II muscle afferents and cutaneous afferents of the most effective nerves were often cut short by disynaptic IPSPs. As a consequence of this negative feedback the EPSPs gave rise to single or double spike potentials and only a minority of interneurones responded with repetitive discharges. However, the neurones that did respond repetitively did so at a very high frequency of discharges (0.8-1.2 ms intervals between the first 2-3 spikes). 4. Sacral dorsal horn group II interneurones do not appear to act directly upon motoneurones because: (i) these interneurones are located outside the area within which last order interneurones have previously been found and (ii) the latencies of PSPs evoked in motoneurones by stimulation of the posterior biceps and semitendinosus, cutaneous femoris and pudendal nerves (i.e. the main nerves providing input to sacral interneurones) are compatible with a tri- but not with a disynaptic coupling. Spatial facilitation of EPSPs and IPSPs following synchronous stimulation of group II and cutaneous afferents of these nerves shows, however, that sacral interneurones may induce excitation or inhibition of motoneurones via other interneurones. 5. Comparison of the properties of group II interneurones in the sacral segments with those of previously studied group II interneurones in the midlumbar segments leads to the conclusion that these two populations of neurones are specialized for the processing of information from different muscles and skin areas. In addition, equivalents of only one of the two subpopulations of midlumbar interneurones have been found at the level of the pudendal nucleus: neurones with input from group II but not from group I muscle afferents. Neurones integrating information from group I and II muscle afferents and in direct contact with motoneurones thus seem to be scarce in the sacral segments.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8006829 TI - Ascending tract neurones processing information from group II muscle afferents in sacral segments of the feline spinal cord. AB - 1. Ascending tract neurones located in the dorsal horn of sacral segments of the spinal cord have been investigated by extracellular and intracellular recording in the anaesthetized cat. The aim was to determine whether information from group II afferents that terminate within the sacral segments is conveyed to supraspinal structures and which types of neurones are involved. 2. A considerable proportion of ascending tract neurones found in the dorsal horn in the same segments as the pudendal (Onuf's) motor nucleus were excited by group II muscle afferents. The great majority (93%) of these neurones had axons ascending in ipsilateral funiculi. Spinocervical tract neurones constituted the largest proportion (82%) of such neurones, while very few spinocerebellar tract and propriospinal neurones and no postsynaptic dorsal column neurones were found among them. 3. In addition to activation by group II muscle afferents all of the neurones were strongly excited by cutaneous afferents. The most potent excitation was evoked by afferents of the posterior biceps-semitendinosus and gastrocnemius muscle nerves and by afferents of the cutaneous femoris, sural and pudendal nerves. The latencies of intracellularly recorded excitatory potentials were indicative of a high incidence of monosynaptic coupling between the afferents and ascending tract neurones. 4. The highly effective monosynaptic excitation of spinocervical tract neurones in the sacral segments by group II afferents is in contrast to the weak disynaptically mediated actions of group II afferents on such neurones in the L6 L7 segments but comparable to the actions of group II afferents on ascending tract neurones in the midlumbar segments. 5. Both the patterns of peripheral input and the latencies of synaptic actions in ascending tract neurones were similar to those in interneurones at the same locations (accompanying report). Similar information is therefore likely to be processed by both categories of neurones. 6. The role of sacral spinocervical tract neurones as a system for transmitting information from group II muscle afferents to supraspinal centres and the potential contribution of this system to the perception of limb position are discussed. PMID- 8006830 TI - Force-velocity relation for frog muscle fibres: effects of moderate fatigue and of intracellular acidification. AB - 1. Intact frog single fibres were investigated under control conditions (1 s tetanus every 2, 3 or 5 min) and during moderate fatigue (interval between tetani 15 or 30 s). 2. Fatigue reduced isometric force (P0) by 25.8 +/- 1.6% (S.E.M.; n = 13) and depressed the maximum velocity of shortening (Vmax) by 10.2 +/- 2.2% (n = 13). The force-velocity relation became less curved, a/P0* (see Methods) being increased by 29.5 +/- 8.8% (n = 13). Thus, power was less affected than isometric force or Vmax. 3. The velocity of unloaded shortening (V0), from slack test measurements, was reduced proportionally more than Vmax during fatigue. Under control conditions V0 was larger than Vmax, but during fatigue their values were not significantly different. 4. Stiffness during shortening was reduced during fatigue indicating fewer attached cross-bridges in fatigue. Force was reduced more than stiffness indicating that, on average, there is less force per attached cross-bridge. 5. The force-lengthening velocity relation showed that the ability to resist forces greater than isometric was well preserved in fatigue. 6. Compared with fatigue, intracellular acidification with CO2 produced a smaller reduction in isometric force. However, reduction in Vmax was not significantly different from that in fatigue. These results are consistent with both inorganic phosphate and H+ increasing in fatigue, but only H+ increasing during acidification, and isometric force being reduced by both, Vmax being sensitive only to H+. PMID- 8006832 TI - Evidence for corticospinal excitation of presumed propriospinal neurones in man. AB - 1. The possibility that stimulation of the motor cortex facilitates transmission in the pathway mediating non-monosynaptic ('propriospinal') excitation from low threshold afferents to upper limb motoneurones was investigated. 2. Convergence between peripheral afferent volleys (from the ulnar or musculo-cutaneous nerve) and corticospinal volleys (evoked by magnetic stimulation of the motor cortex) was investigated using the spatial facilitation technique. Thus the effects of these volleys on the flexor carpi radialis H reflex were compared when applied separately and together. When cortical stimulation was optimal for the muscle from which the conditioning volley originated the facilitation of the reflex on combined stimulation was significantly larger than the algebraic sum of the effects of separate stimuli. 3. The extra facilitation on combined stimulation had all the characteristics of 'propriospinal' excitation (low threshold, long central delay, brief duration and depression when the afferent input was increased), and it is suggested that this reflects corticospinal excitation of 'propriospinal' neurones. 4. When varying the time interval between cortical and test stimulations, it was shown that extra facilitation on combined stimulation began 1 ms later than the onset of the control reflex facilitation. Assuming that the latter onset reflects the arrival of the monosynaptic corticospinal volley at the motoneurone pool, this 1 ms delay suggests a disynaptic pathway for the cortical excitation of motoneurones through 'propriospinal' neurones. 5. As at the onset of voluntary movement, the pattern of the cortical excitation of 'propriospinal' neurones was quite specific: extra facilitation of the reflex on combined stimulation only occurred when the cortical volley was preferentially directed to motoneurones supplying the muscle from which the afferents used for the peripheral volley originated. 6. It is concluded that corticospinal axons activate human 'propriospinal' neurones and thereby produce disynaptic excitation of the motoneurone pool. Given temporal summation with the monosynaptic excitation, this 'propriospinally mediated' disynaptic excitation might make a significant contribution to the evoked EMG potential. PMID- 8006831 TI - The effect of glibenclamide on frog skeletal muscle: evidence for K+ATP channel activation during fatigue. AB - 1. The purpose of this study was to determine whether ATP-sensitive K+ (K+ATP) channels are activated and contribute to the decrease in force during fatigue development in the sartorius muscle of the frog, Rana pipiens. Tetanic force (elicited by field stimulation), action potential and membrane conductance (using conventional microelectrodes), were measured in the presence and absence of glibenclamide, a K+ATP channel antagonist. Experiments were performed in bicarbonate-buffered solutions at pH 7.2. 2. In unfatigued muscle 100 mumol l-1 glibenclamide had no effect on the resting potential, the overshoot, the half depolarization time or the maximum rate of depolarization of action potentials, while the mean half-repolarization time increased by 19 +/- 4% (+/- S.E.M.) and the maximum rate of repolarization decreased by 17 +/- 5%. 3. Fatigue was elicited using 100 ms tetanic contractions every 1 s for 3 min. In the absence of glibenclamide the mean half-repolarization time increased from 0.57 +/- 0.05 to 0.89 +/- 0.05 ms during fatigue. The mean half-repolarization times after fatigue, when muscle fibres were exposed to 100 mumol l-1 glibenclamide either 60 min prior to fatigue or 60 s before the end of fatigue, were 1.16 +/- 0.08 and 1.17 +/- 0.07 ms respectively. Application of 100 mumol l-1 glibenclamide after 5 min of recovery did not increase the half-repolarization time, but decreased the rate of recovery compared to control values. 4. In unfatigued muscles, 100 mumol l-1 glibenclamide did not affect the tetanic contraction. In the absence of glibenclamide, the mean tetanic force after fatigue was 11.0 +/- 0.9% of prefatigue values. Application of 100 mumol l-1 glibenclamide 60 min before fatigue increased the rate of fatigue development as the mean tetanic force was 4.8 +/- 0.8% after 3 min of stimulation. The addition of 100 mumol l-1 glibenclamide 60 s before the end of fatigue had no effect on tetanic force during this time compared to control. 5. In the absence of glibenclamide, muscles recovered 90.1 +/- 1.6% of their tetanic force after 100 min. Addition of 100 mumol l-1 glibenclamide 60 min prior to fatigue significantly reduced the capacity of muscles to recover their tetanic force: after 100 min of recovery tetanic force was only 47.3 +/- 9.4% of the pre-fatigue value.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8006833 TI - Reflex recruitment of medullary gasping mechanisms in eupnoea by pharyngeal stimulation in cats. AB - 1. Mechanical stimulation of the naso- and oropharynx causes the replacement of the eupnoeic ventilatory pattern by a brief, but large, burst of activity of the phrenic nerve. Our purpose was to define whether these changes in phrenic activity represent a switch to gasping. 2. In decerebrate, vagotomized, paralysed and ventilated cats, mechanical stimulation of the pharynx was performed during eupnoea, apneusis and gasping. The latter two ventilatory patterns were produced by ventilating the experimental animal with 1.0% carbon monoxide in air or with 100% nitrogen. Eupnoea could be re-established by a recommencement of ventilation with oxygen. 3. The rate of rise of phrenic activity and its peak height were much greater following mechanical stimulation of the pharynx than the phrenic bursts of eupnoea or apneusis. The durations of phrenic burst and the period between these were much less following pharyngeal stimulation. In contrast, these variables of phrenic activity were the same during pharyngeal stimulation and in gasping. 4. Previous studies had established that activity within a region of the lateral tegmental field of medulla is critical for the manifestation of gasping. Hence, electrical stimulation of this region during gasping elicits premature gasps whereas its ablation irreversibly eliminates gasping. 5. We positioned a multibarrelled pipette in the critical medullary region for gasping. Its location was verified, once gasping was established in hypoxia or anoxia, by the elicitation of premature gasps following electrical stimulation. Neurons in this region were destroyed by microinjections of the neurotoxin kainic acid; in a few experiments the region was destroyed by electrolytic lesions. 6. Following destruction of the region of the lateral tegmental field, gasping could no longer be provoked in anoxia. In contrast, the eupnoeic pattern of phrenic activity continued. However, mechanical stimulation of the pharynx no longer caused any changes in the on-going pattern of phrenic activity. 7. We conclude that mechanical stimulation of the pharynx elicits a powerful reflex by which eupnoea is suppressed and gasping is elicited. Stated differently, the changes in phrenic activity during this pharyngeal stimulation in fact represent gasps. 8. Gasps are dependent upon activity within a region of the lateral tegmental field of the medulla. This region plays no role in the neurogenesis of eupnoea. Hence, our results provide additional support for the concept that there are multiple sites for ventilatory neurogenesis in the mammalian brainstem. PMID- 8006835 TI - Differential secretion of catecholamines in response to peptidergic and cholinergic transmitters in rat adrenals. AB - 1. Rat adrenal medulla is stimulated by cholinergic and peptidergic transmitters released from splanchnic nerves. The peptidergic transmitter has been identified as vasoactive intestinal polypeptide (VIP) and its contribution in comparison to that of acetylcholine (ACh) is more prominent at low neuronal activity. The purpose of this study is to determine if ACh and VIP cause differential secretion of adrenaline and noradrenaline and whether the differential secretion also occurs when splanchnic nerves are stimulated at different frequencies. 2. Perfusion of the left adrenal gland with Krebs solution for several hours did not change adrenaline and noradrenaline contents (15.2 micrograms and 3.5 micrograms, respectively) and their ratio (4.4) from those of the unperfused right adrenal medulla (15.2 micrograms, 3.3 micrograms and 4.8, respectively). 3. Perfusion with ACh (10 microM for 4 min) resulted in the secretion of 109 ng of catecholamines and the ratio of adrenaline to noradrenaline was 3.8. Although the secretion increased with increased concentrations of ACh (30 and 100 microM), the ratios remained between 3 and 4. 4. Perfusion with VIP (10 microM for 4 min) resulted in the secretion of 27 ng of catecholamines and the ratio of adrenaline to noradrenaline was 9.7. A higher concentration of VIP (20 microM for 4 min) resulted in the secretion of greater amounts of catecholamines (102 ng) without significantly altering the ratio of adrenaline to noradrenaline (10.9). 5. Perfusion with as low as 0.01 microM pituitary adenylate cyclase-activating polypeptide (PACAP) increased the secretion of catecholamines to 31 ng and the secretion increased in a dose-dependent manner up to 0.3 microM.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8006834 TI - Enterotoxin Escherichia coli STa activates a nitric oxide-dependent myenteric plexus secretory reflex in the rat ileum. AB - 1. Mucosally added enterotoxin Escherichia coli STa increased the electrogenic Cl secretion measured as the short-circuit current (Isc) across isolated muscle stripped and muscle-unstripped rat mid-ilea incubated in vitro. 2. Pretreatment with serosal L-NAME (N omega-nitro-L-arginine methyl ester) or tetrodotoxin (TTX) significantly reduced the maximum Isc and the duration of action of STa in the unstripped but not stripped ilea. D-NAME (serosal), indomethacin or 5-hydroxy tryptamine-desensitization was ineffective on STa-induced Isc in either stripped or unstripped ilea. 3. Serosal capsaicin reduced the maximum Isc of STa and its duration of action in unstripped ilea. 4. L-Arginine induced a significantly larger increase in the Isc across unstripped ilea than across stripped ilea; this could be significantly reduced by serosal L-NAME or TTX, although these were ineffective in stripped ilea. 5. Pretreatment of anaesthetized rats with I.P. L NAME suppressed the fluid secretion induced by luminal STa in ilea in vivo but had no effect on that induced by luminal carbachol. 6. Mucosal STa increased electrogenic Cl- secretion across intact rat ileum in vitro by activating a capsaicin-sensitive, nitric oxide-dependent myenteric plexus-mediated secretory reflex. The suppression by L-NAME of STa induced ileal fluid secretion in vivo probably involves the inhibition of this reflex. PMID- 8006836 TI - Finite element analysis estimates of cement microfracture under complete veneer crowns. AB - Long-term clinical failures of complete veneer crowns are commonly attributed to microleakage of the cement. Excessive stress or fatigue cycling may create cement microfractures and promote microleakage. Two-dimensional (2D) finite element analysis (FEA) was selected to determine stress levels and distributions on dental cements resulting from 10 MPa occlusal loads on single-unit complete artificial veneer crowns during various clinical conditions. Sixteen 2D-FEA computer models were generated for a mandibular first premolar to study the effects of (1) marginal configuration (shoulder for all-ceramic crown versus chamfer for type III gold alloy crown), (2) four types of cement (zinc phosphate, polycarboxylate, glass ionomer and composite resin), and (3) two thicknesses of cement (25 and 100 microns) for single-cycle loads and fatigue loading. There was almost no difference between a chamfer and shoulder marginal configuration except at the edge of the margin where the chamfer finish lines reached 2 to 8 times greater stresses. There were minimal effects for thickness of cement and marginal configurations. Stresses were slightly less for thicker cement. Fatigue analysis was based on estimated stress versus number of cycle curves for cements and resulted in stresses below the estimated endurance limit. If the average occlusal loading levels were 10 MPa, there did not appear to be a risk of microfracture in dental cement because of mechanical loading. PMID- 8006837 TI - Gingival reaction on crowns with cast and sintered metal margins: a progressive report. AB - Sintered metals have been developed recently for the construction of metal ceramic crowns (Degusint U). An unbalanced, randomized double-blind study was conducted to compare the gingival response to artificial crowns with sintered noble metal margins and cast noble metal margins (Degudent U) by measuring the sulcus-fluid-flow rate (SFFR) in highly motivated patients. In a prior study marginal opening of 20 microns were recorded for cast metal crowns, whereas two sintered metal crowns had marginal openings of 40 microns. Three metal ceramic crowns (Renaissance, Degusint U, and Degudent U for the copings and VMK 68 porcelain) with subgingival margins were prepared and fabricated for 12 intact natural teeth. The SFFR was measured for teeth with artificial crowns and adjacent natural teeth after provisional insertion of each crown. Significantly elevated SFFRs were recorded for all artificial crowns compared with the adjacent natural teeth, but there were no variations recorded for the different types of crown margins. PMID- 8006838 TI - Effect of ultrasonic cleaning and air polishing on porcelain labial margin restorations. AB - This study examined porcelain labial margins after ultrasonic scaling and air polishing. Thirty metal coupons were covered with 1.5 mm thick shoulder porcelain and cemented to acrylic resin blocks. A reference mark divided each specimen into a "treated" and an "untreated" side. The specimens were treated as three groups with: (1) an air polisher; (2) an ultrasonic scaler, and (3) the ultrasonic scaler and the air polisher. Surface roughness was determined and selected specimens were observed under scanning electron microscope. Surface roughness ranged from 0.37 microns to 1.06 microns for the untreated sides and from 0.86 microns to 2.80 microns for the treated sides. Increases in roughness were 69% for the ultrasonic scaler/air-polisher; 127% for the air polisher, and 162% for the ultrasonic scaler. ANOVA indicated a significant difference between the treatments. Specimens treated with the air polisher or the ultrasonic scaler and air polisher combination were less distorted than those treated with the ultrasonic scaler alone. The data suggested that careless use of an ultrasonic scaler or air polisher could substantially alter porcelain facial margins. PMID- 8006839 TI - Sandblasting and silica coating of a glass-infiltrated alumina ceramic: volume loss, morphology, and changes in the surface composition. AB - Silica coating can improve bonding of resin to glass-infiltrated aluminum oxide ceramic (In-Ceram), and sandblasting is a pretreatment to thermal silica coating (Silicoater MD system) or a tribochemical coating process (Rocatec system). This study evaluated the effects of sandblasting and coating techniques on volume loss, surface morphology, and surface composition of In-Ceram ceramic. Volume loss through sandblasting was 36 times less for In-Ceram ceramic compared with a feldspathic glass ceramic (IPS-Empress), and sandblasting of In-Ceram ceramic did not change its surface composition. After tribochemical coating with the Rocatec system, a layer of small silica particles remained that elevated the silica content to 19.7 weight percentage (energy-dispersive spectroscopy). Ultrasonic cleaning removed loose silica particles from the surface and decreased the silica content to 15.8 weight percentage, which suggested firm attachment of most of the silica layer to the surface. After treatment with the Silicoater MD system, the silica content increased only slightly from that of the sandblasted specimen. The silica layer created by these systems differs greatly in both morphology and thickness, which could result in different bond strengths. Sandblasting of all ceramic clinical restorations with feldspathic glass materials should be avoided, but for In-Ceram ceramic the volume loss was within an acceptable range and similar to that of noble metals. PMID- 8006840 TI - Fracture strength of full-contoured ceramic crowns and porcelain-veneered crowns of ceramic copings. AB - This is vitro study compared the fracture strength of Dicor ceramic crowns with a 1 mm axial wall thickness and a 2 mm occlusal thickness with Dicor copings veneered with Vitadur-N or Dicor-Plus porcelain to create similar contours. Tooth preparations for complete crowns were made on human molars with a 10-degree total convergence and a 1 mm shoulder. The artificial crowns were internally etched, given an application of silane, and cemented with a dual-cured resinous cement. After thermocycling, each sample was loaded to failure with a vertical load on the occlusal surface. There were no significant differences in fracture strength between full-contour Dicor crowns and crowns of copings veneered with either Vitadur-N or Dicor-Plus porcelain. PMID- 8006842 TI - How severe is the threat of caries to old teeth? AB - Caries is a bacterial infection caused by a complex interaction of biologic and behavioral factors. It is believed that caries is a major threat to teeth in old age, yet little information is available on the incidence and progress of carious lesions in elderly teeth. All too often caries is diagnosed after a visual and tactile examination of tooth structure without thought for the other factors essential to the initiation and support of an active lesion. Prospective studies have been conducted recently in Vancouver to quantify associations between the incidence of caries and many of the behavioral, bacteriologic, and physiologic factors potentially influencing oral health in old age. The results indicate that improvements in hygiene may hold the most promise for controlling this infection in an elderly population. PMID- 8006841 TI - Flexural strength of feldspathic porcelain treated with ion exchange, overglaze, and polishing. AB - Feldspathic porcelains, which are used in the construction of porcelain-fused-to metal (PFM) restorations, have an inherent weakness because of their brittle nature and processing flaws. A relatively new product, the Tuf-Coat ion exchange system, claims to substantially strengthen feldspathic porcelains. This study compared the strengthening effect of the Tuf-Coat system with that of surface treatments such as overglazing, polishing, and finishing. Bend bars of Vita VMK 68 porcelain were made and randomly assigned to eight different surface treatment groups to examine these effects. The flexural strengths revealed that although Tuf-Coat treatment strengthened the porcelain, it was not significantly different from overglazing, and the strengthening effect was lost if the porcelain was subsequently self-glazed or finished. PMID- 8006843 TI - Alveolar bone resorption: a histologic study comparing bone turnover in the edentulous mandible and iliac crest. AB - The extent of bone formation and resorption in alveolar and basal mandibular bone was measured in 17 edentulous individuals. For comparison, samples of iliac crest bone were also collected because this bone is often used for standard site assessment of skeletal measures of bone turnover. The specimens were processed for undecalcified resin histology. The results indicated extensive bone resorption at the periosteal surface of the alveolar crest, with little evidence of subsequent osteoid formation. Endosteal osteoid formation did occur, which tended to maintain the thickness of the cortical bone at the alveolar crest. Mandibular basal bone displayed a remodeling pattern similar to that seen in the iliac crest. PMID- 8006844 TI - A diagnostic stent for endosseous implants to improve conventional tomographic radiographs. AB - Conventional tomographic radiographs can often provide sufficient information for presurgical evaluation for implant placement with significantly less radiation exposure than computer-assisted tomographic (CT) radiographs. A technique to fabricate a diagnostic stent with a removable indicator for the partially edentulous patient is described. This stent with an indicator guides the radiologist in making conventional tomographic images and can also be used as a template for locating the surgical sites. PMID- 8006845 TI - A comparative prospective study of splinted and unsplinted Branemark implants in mandibular overdenture therapy: a preliminary report. AB - Thirty-six edentulous patients, each provided with two Branemark implants in the mandible to anchor an overdenture, were selected for this study and randomly divided into three groups of 12 patients each. In each group a different attachment system was used: (1) magnets, (2) ball attachments, and (3) straight bars with clips (control). The mean loading time was 12.4 months (range 3 to 24 months). This study investigated (1) the clinical behavior of loaded implants by means of overdentures related to their connection system (splinted versus unsplinted) and (2) the clinical performance of prosthetic treatment. Preliminary results indicate no differences; no failures occurred and the level of marginal bone height, as well as the probing attachment level, changed similarly in the three groups. Although splinted bar-retained overdentures scored better objectively, subjective satisfaction ratings did not differ. It was concluded that for the short follow-up period, the state of connection did not influence the clinical success of implants. However, no definite conclusions may be drawn until long-term data become available. PMID- 8006846 TI - Effect of cantilever length on stress transfer by implant-supported prostheses. AB - Cantilever lengths for fixed implant supported prostheses have been based largely on empirical judgment. This study determined the effects of cantilever length on load transfer to the mandible. A photoelastic model of a moderately resorbed edentulous human mandible with five 13 mm Branemark implants was constructed. Simulated occlusal loads at varying cantilever lengths were applied to the occlusal surface of a routinely fabricated fixed prosthesis. The highest stresses were located at the ridge crest on the distal surface of the distal implant for all cantilever lengths. Apical stresses at this implant developed in reciprocation to the effect of the distal tipping force on the cantilever. Curves describing the effect of cantilever length on maximal stress are presented. Little load transfer to adjacent implants was found. Disproportionate increases in maximum stress with increasing cantilever length occurred. Minor variations in implant angulation had a distinct effect on stress magnitude. PMID- 8006848 TI - Effects of RTC-silicone maxillofacial prosthetic elastomers on cell cultures. AB - The use of a wide variety of materials in the construction of maxillofacial prostheses makes biocompatibility testing a necessity. However, the dental literature contains few reports of biocompatibility testing of maxillofacial prosthetic materials. The cytotoxic profiles of five room-temperature cross linking (RTC)-silicone elastomers were investigated by means of two in vitro cell culture techniques. Mouse fibroblast cells (L929) were used, and the results indicated that RTC-silicone elastomers adversely affected cells in culture and that storage of samples for 1 week in saline solution did not alter this effect. Clinical follow-up of patients wearing prostheses made of these silicone materials is warranted to evaluate host reactions in long-term contact with human mucous membrane and skin tissue. PMID- 8006847 TI - An assessment of the physical properties and biocompatibility of three silicone elastomers. AB - The physical properties of two room-temperature vulcanizing (RTV) silicones, A 2186 and Silbione 71556, and one high-temperature vulcanizing (HTV) material, Mollomed, were compared. The potential cytotoxicity of the silicone materials was assessed with the agarose overlay test. The properties that were investigated were tensile strength, percentage elongation, modulus, permanent set, tear strength, and hardness. The properties tested were selected because of their clinical significance for fabricating facial prostheses. The results of this study indicate that the A-2186 material has a better combination of high tear strength and elongation at break with a softer surface compared with Mollomed silicone, and Silbione 71556 silicone proved to be the weakest material. All materials demonstrated absence of cytotoxicity in the cell culture tests. PMID- 8006849 TI - Crown pattern waxes: a study of their behavior on heating and cooling. AB - The values of the critical physical properties, flow and linear thermal expansion, of crown pattern waxes were determined and compared with those reported by previous investigators. The method is one proposed by the American Dental Association, and measurements were conducted in the temperature range of 27 to 52 degrees C. At temperatures higher than 37 degrees C most of the materials tested exhibited flow values that although rather low seem to be suitable for laboratory use. As expected, the linear thermal expansion was considerable, ranging from 1% to 1.5% or more as the temperature was increased from 27 degrees to 47 degrees C. The arrest points of the cooling curves, which are indicative of the composition of the materials, were recorded and studied. The possibility of correlating the arrest points with the transition points observed on the flow and expansion curves was investigated. Although attempts have been made to improve them, the commonly used dental waxes are not yet entirely free of their known drawback of large and perhaps uncontrollable thermal expansion. PMID- 8006850 TI - Use of a new assay technique for quantification of antifungal activity of nystatin incorporated in denture liners. AB - Denture-induced stomatitis with concurrent candidal infection is the most commonly encountered intraoral abnormality among individuals who wear dentures. The institutionalized elderly demonstrate increased susceptibility and could benefit from its management with a fungicidal denture liner. As an integral part of the prosthesis, the efficacy of the fungicidal liner would be independent of patient compliance and/or nursing involvement and would provide a predictable therapeutic modality. In this study a "slant agar assay" was developed to evaluate the in vitro antimycotic activity of Visco-gel and Lynal liners impregnated with various concentrations of nystatin over a 14-day period in nonaqueous and aqueous environments. The results were as follows: preparations incorporating higher concentrations of nystatin resulted in greater inhibition of Candida albicans growth; Visco-gel liner-nystatin preparations exhibited a greater fungicidal activity than equivalent Lynal preparations; loss of potency by all of the reline-nystatin preparations consisted of an initial rapid loss between days 0 and 2, followed by a plateau during which the preparations gradually continued to lose inhibitory activity; and 1 million units of nystatin were necessary to maintain an adequate level of antifungal activity in an aqueous environment, where the liners demonstrated decreasing antifungal activity proportional to the duration of exposure to water. PMID- 8006851 TI - Comparison of tensile and peel bond strengths of resilient liners. AB - Previous studies have shown little agreement between the test methods used to assess the bond strength and the mode of failure of resilient liners. This study evaluated the bond strength characteristics of resilient liners by means of 180 degree peeling and butt tensile strength testing. Seventy-two specimens were divided into peel bond and tensile bond specimen groups and were then subdivided into four test groups to evaluate each resilient liner. Tests were conducted with an Instron universal testing machine at a cross-head speed of 2 mm/minute for the tensile specimens and 5 mm/min for the peel specimens. Tensile bond strength and peel bond strength varied significantly among resilient liners except between Novus and Palasiv-62 liners in tensile testing. The mode of failure of Molloplast B and Novus liners was significantly different between the tensile bond and peel bond test methods. It was concluded that bond strength characteristics can vary according to the test method used. PMID- 8006853 TI - Removal of enamel surface stains using a new material. PMID- 8006852 TI - Custom impression trays. Part III: A stress distribution model. AB - All resins used to make custom impression trays exhibit plastic deformation at some force value; therefore it is important to compare the physical property values of such materials with the stresses to which impression trays are subjected during dental procedures. A simple mathematical model of a custom tray was developed to predict stress distributions in this final part of a three-part investigation. Experimental stress analysis of such a tray confirmed the accuracy of the model, which was then used to predict the maximum stress experienced by the tray during removal of a completed impression from the oral cavity. The results of this analysis indicated that these stresses would be significantly lower than the yield stress for a commonly used polymethyl methacrylate resin or a light-polymerized resin. The stresses were also sufficiently low for us to conclude that thermoplastic resins would not permanently deform; however, the stresses encountered in the experimental confirmation procedure were close to the yield stress values for these materials. PMID- 8006854 TI - A modified instrument for removing a fractured abutment screw. PMID- 8006855 TI - Electrophysiological measurements of spectral mechanisms in the retinas of two cervids: white-tailed deer (Odocoileus virginianus) and fallow deer (Dama dama). AB - Electroretinogram (ERG) flicker photometry was used to study the spectral mechanisms in the retinas of white-tailed deer (Odocoileus virginianus) and fallow deer (Dama dama). In addition to having a rod pigment with maximum sensitivity (lambda max) of about 497 nm, both species appear to have two classes of photopic receptors. They share in common a short-wavelength-sensitive cone mechanism having lambda max in the region of 450-460 nm. Each also has a cone having peak sensitivity in the middle wavelengths, but these differ slightly for the two species. In white-tailed deer the lambda max of this cone is about 537 nm; for the fallow deer the average lambda max value for this mechanism was 542 nm. Deer resemble other ungulates and many other types of mammal in having two classes of cone pigment and, thus, the requisite retinal basis for dichromatic color vision. PMID- 8006856 TI - Complex sound analysis in the lesser bulldog bat: evidence for a mechanism for processing frequency elements of frequency modulated signals over restricted time intervals. AB - A stereotypical approach phase vocalization response of the lesser bulldog bat, Noctilio albiventris, to artificial echoes simulating a virtual approaching object was used to assess the ability of the bat to analyze and extract distance information from the artificial echoes. The performance of the bat was not significantly different when presented with naturally structured CF/FM echoes containing FM elements that sweep continuously from about 75-55 kHz in 4 ms or with CF/FM echoes containing FM components constructed from a series of 98 pure tone frequency steps, each with a duration of 0.04 ms. The performance of the bat remained unchanged when the duration of the tone steps was increased up to 0.08 ms but declined sharply to a level that was significantly below that seen with a naturally structured echo when the steps were 0.09 ms or longer. The performance of the bat depended on the duration of the individual tone steps, which could not exceed a specific upper limit of about 0.08 ms. The study suggests that the bats have adaptations for processing individual narrow band segments of FM signals over specific time intervals. PMID- 8006857 TI - Complex sound analysis in the FM bat Eptesicus fuscus, correlated with structural parameters of frequency modulated signals. AB - Big brown bats, Eptesicus fuscus, were presented with artificial frequency modulated (FM) echoes that simulated an object becoming progressively closer to the bat. A stereotyped approach phase behavioral response of the bat to the virtual approaching target was used to determine the ability of the bat to analyze FM signals for target distance information. The degree to which the bats responded with approach phase behavior to a virtual approaching target was similar when they were presented with either a naturally structured artificial FM echo or an artificial FM echo constructed from a series of brief pure tone steps. The ability of the bats to respond to an FM signal structured from a sequence of pure tone elements depended on the number of pure tone steps in the series; the bats required the presentation of tone-step FM signals containing about 83 or greater pure tone elements. Moreover, the duration of the individual tone steps of the tone-step FM signals could not exceed a specific upper limit of about 0.05 ms. Finally, it appears that the bats were able to independently resolve individual tone steps within the tone-step FM signals that were separated by about 450 Hz or more. PMID- 8006858 TI - Morphological and electrophysiological consequences of unilateral pre- versus postganglionic vestibular lesions in the frog. AB - The combined removal of the labyrinthine sense organs and of the ganglion of Scarpa on one side (postganglionic section) resulted in a degeneration of afferent fibres in the eighth nerve of the frog (Rana temporaria) within 2-4 days. If the eighth nerve was sectioned more peripherally (preganglionic section) and its distal part was removed together with the labyrinthine organs degeneration of afferent fibres was absent or restricted to very few fibres. Electrical stimulation of vestibular afferents in vitro evoked monosynaptic field potentials in the ipsilateral and via commissural fibres di- and polysynaptic field potentials in the contralateral vestibular nuclei. Afferent-evoked field potentials recorded on the intact side of chronic frogs (> or = 60 days) with a pre- or postganglionic lesion and afferent-evoked field potentials recorded on the operated side of chronic frogs with a preganglionic lesion had amplitudes that were very similar to those recorded in control frogs. Commissurally evoked field potentials recorded on the operated side of chronic frogs with pre- or postganglionic lesions were significantly increased (by about 90%) with respect to control amplitudes. In both groups the time-course of this increase was very similar, started between 15 and 30 days and saturated for survival periods longer than 60 days. Unilateral inactivation of vestibular afferents, but not degeneration, is the likely common denominator of the central process leading to the reported neural changes. A reactive supersensitivity of central vestibular neurons on the operated side for glutamate as a possible mechanism is unlikely, since converging afferent and commissural inputs are both glutamatergic and only one of them, the commissural input, was potentiated. Comparison of the time courses of neural changes in the vestibular nuclei and postural recovery in the same individuals excludes a causal relation between both phenomena. PMID- 8006859 TI - Substrate-gleaning versus aerial-hawking: plasticity in the foraging and echolocation behaviour of the long-eared bat, Myotis evotis. AB - The foraging and echolocation behaviour of Myotis evotis was investigated during substrate-gleaning and aerial-hawking attacks. Bats gleaned moths from both the ground and a bark-covered trellis, however, they were equally adept at capturing flying moths. The calls emitted by M. evotis during substrate-gleaning sequences were short, broadband, and frequency-modulated (FM). Three behavioural phases were identified: search, hover, and attack. Gleaning search calls were significantly longer in duration, lower in highest frequency, and larger in bandwidth than hover/attack calls. Calls were detected in only 68% of gleaning sequences, and when they were emitted, bats ceased calling approximately 200 ms before attacking. Terminal feeding buzzes, the rapid increase in pulse repetition rate associated with an attempted prey capture, were never recorded during gleaning attacks. The echolocation calls uttered by M. evotis during aerial hawking foraging sequences were also short duration, high frequency, FM calls. Two distinct acoustic phases were identified: approach and terminal. Approach calls were significantly different from terminal calls in all variables measured. Calls were detected in 100% of aerial-hawking attacks and terminal feeding buzzes were invariably produced. Gleaning hover/attack calls were spectrally similar to aerial approach calls, but were shorter in duration and emitted at a significantly lower (but constant) repetition rate than aerial signals. Although the foraging environment (flight cage contents) remained unchanged between tasks (substrate-gleaning vs. aerial-hawking), bats emitted significantly lower amplitude calls while gleaning. We conclude that M. evotis adjusts its echolocation behaviour to meet the perceptual demands (acoustical constraints) imposed by each foraging situation. PMID- 8006860 TI - High hopes ... for neurology. A view from the top. PMID- 8006861 TI - High hopes ... for neurology--looking to the top. PMID- 8006862 TI - Brain repair. AB - Diseases of the human brain and spinal cord are common and often progressive since, unlike peripheral nerve, the adult human central nervous system does not spontaneously repair itself. Studies on development and cell lineages in the nervous system have started to elucidate the scientific basis for this lack of regeneration, and have suggested ways of enhancing repair. At the same time, improved understanding of neurodegenerative processes has provided a rationale for treatments which limit neuronal and glial damage. Cell implantation has been tested, experimentally and in man, and with some prospects for successful restoration of normal cell arrangements in the central nervous system. Taken together, a coherent strategy for limiting the damage and repairing the brain is beginning to emerge. The translation of these ideas into clinical practice is timely and eagerly awaited. PMID- 8006863 TI - Genetic mechanisms and mental retardation. AB - The past five years have witnessed rapid and apparently relentless progress in the delineation of the genetic basis of disorders associated with mental retardation. Each gene discovery has a new story to tell but inevitably generates further questions. For the clinical geneticist and, perhaps more importantly, for patients and their families, many of these recent discoveries have yielded information which has immediate implications for diagnostic testing, family and population screening and prenatal testing. Many of the ethical issues consequent upon the rapid progress are only now being addressed. This article highlights a number of disorders whose molecular genetic basis has recently been further characterised. Brain development and maintenance of neurological networks provide the unifying theme; the genetic defects are disparate and each of their mechanisms appears to be novel. PMID- 8006864 TI - Noninvasive assessment of cerebral oxidative metabolism in the human newborn. AB - Magnetic resonance spectroscopy (MRS) and near infrared spectroscopy (NIRS) permit direct observations within the human brain of a number of metabolites important in cerebral oxidative metabolism. MRS identifies high energy phosphorus metabolites such as phosphocreatine and ATP, which are products of oxidative phosphorylation and of the anaerobic accumulation of lactate. NIRS makes it possible to measure cerebral haemodynamics and oxygen delivery and to detect changes in the redox state of mitochondrial cytochrome oxidase. Studies in the brain of newborn infants after perinatal asphyxia have shown a delayed reduction in high energy phosphorus metabolites and an accumulation of lactate. Haemodynamic abnormalities frequently precede the delayed failure of energy metabolism. NIRS and MRS provide unique information on deranged cerebral energy metabolism following hypoxia-ischaemia and will guide the introduction of new cerebroprotective interventions. PMID- 8006865 TI - Fragrance: its biology and pathology. PMID- 8006866 TI - Some aspects of cancer medicine. AB - The role of molecular oncology in understanding the nature of the cancer cell, and as an aid to diagnosis and even therapy, is discussed and illustrated with examples from commonly occurring malignancies. The appreciation of the importance of cell biology in explaining why cells become resistant to anticancer drugs has developed rapidly, and examples are given. Cell biology and molecular biology contribute to cancer prevention, which is becoming a practical possibility. Haemopoietic growth factors make it possible to give more intensive chemotherapy treatments and to improve the survival rate in patients with chemoresponsive disease. Intensification, however, has to be balanced against the risk of both short-term and, more seriously, long-term toxicity. PMID- 8006867 TI - Myocardial infarction and thrombolysis: a comparison of the Indian and European populations on a coronary care unit. AB - We reviewed the ward admission notes of 211 Indian and 192 European patients admitted over a period of 12 months to a coronary care unit. More Indian patients had myocardial infarctions (34% vs 27%, p < 0.05); they were more likely to have diabetes mellitus (47% vs 14%, p < 0.001), but less likely to smoke (19% vs 67%, p < 0.001). Fewer Indian patients were treated with thrombolysis (49% vs 80%, p < 0.001), late presentation being the principal reason (62% vs 40%, p < 0.05). The referral rates for exercise stress testing and cardiac catheterisation were not significantly lower for Indian patients. The Indian patient admitted into a coronary care unit is more likely to have had a myocardial infarction and yet less likely to receive care comparable to that of his European counterpart. PMID- 8006868 TI - London--the European centre of excellence. PMID- 8006870 TI - Continuing Medical Education for physicians. PMID- 8006869 TI - Local research ethics committees. Widely differing responses to a national survey protocol. AB - The diversity in responses of local research ethics committees (LRECs) is illustrated with reference to consideration of the protocols for a national survey of physical activity, fitness and health in healthy volunteers. The survey included a questionnaire administered in the home, followed by a physical appraisal carried out in a mobile laboratory. The study was eventually approved by the 30 local committees to which it was submitted, but there was marked variation in the type of enquiries received and the special arrangements requested. At one extreme, some committees approved the study before seeing the detailed ethical submission; at the other extreme, suggested expensive and time consuming alterations to the standard procedures. Our experience reveals a lack of uniformity in the operation of LRECs, serious enough to delay and even inhibit useful research, and a failure of some committees to adhere to guidelines suggested by the Royal College of Physicians and the Department of Health. PMID- 8006871 TI - Science and/or medicine: the Cambridge medical curriculum controversy of the 1930s. PMID- 8006872 TI - Medical Benefit/Risk Foundation--a new charitable foundation for the safer use of medicines. PMID- 8006873 TI - The inauguration of the Hong Kong Academy of Medicine. PMID- 8006874 TI - Little things mean much to neurologists. PMID- 8006875 TI - 'A case of fever, attended with inordinate appetite'. A report delivered and recorded in 1815. PMID- 8006876 TI - Physicians' attitudes to the autopsy. PMID- 8006877 TI - Standards for the hospital management of stroke patients. PMID- 8006878 TI - Pejorative drift of medical words: geriatric, elitist. PMID- 8006879 TI - Musculoskeletal disability and rheumatology. PMID- 8006880 TI - Seronegative rheumatoid arthritis: tell it as it is. PMID- 8006881 TI - Systemic lupus erythematosus--disease activity, severity, treatment and costs. PMID- 8006882 TI - Vasculitis in the antiphospholipid syndrome: culprit or consort? PMID- 8006883 TI - Synergism of interleukin 1 and interleukin 6 induces serum amyloid A production while depressing fibrinogen: a quantitative analysis. AB - OBJECTIVE: Production of the serum amyloid A (SAA) proteins in the liver of patients with arthritis can be increased from approximately 1 microgram/ml to > 1000 micrograms/ml, while fibrinogen (Fg) can be increased from 2 to 9 mg/ml. The increases appear to be regulated by mediators similar to those found in inflamed joints, e.g., interleukins 1 and 6 (IL-1 and IL-6, respectively). The sensitivity and dose response of SAA and Fg synthesis by hepatoma cells to IL-1 and IL-6 was investigated to understand the relationship between the inflammatory cytokines produced in inflamed joints and the acute phase protein response in the liver of arthritis patients. METHODS: SAA and Fg mRNA and protein production in human Hep3B cells stimulated by human monocyte conditioned medium (CM) containing known amounts of IL-1 and IL-6, or stimulated by corresponding concentrations of recombinant IL-1 and IL-6 was analyzed by ELISA and Northern blot hybridization techniques. RESULTS: Increases in SAA mRNA and protein were dose dependent in the presence of IL-1 and IL-6 at concentrations ranging from 0.1 and 1 ng/ml, respectively, to 10 and 100 ng/ml, respectively. In the presence of IL-1 receptor antagonist (IL-1ra), there was a 75% decrease in SAA production and > 100% increase in Fg production by cells stimulated with CM. CONCLUSION: Our results demonstrate that the thousand fold dynamic range associated with the acute phase SAA response requires IL-1 acting synergistically with cytokine(s) like IL-6. Optimum conditions for apoSAA production are suboptimal for Fg as indicated by the differential effects of IL-1ra. PMID- 8006884 TI - Cytokine induction of adhesion molecules on synovial type B cells. AB - OBJECTIVES: To study the role of cytokines on adhesion molecule expression and binding of activated T cells to synovial type B cells. METHODS: Adhesion molecule expression was examined by immunofluorescence and adhesion of 51Cr-labelled T cells to the synovial cells determined. RESULTS: Tumor necrosis factor alpha/interferon gamma (TNF alpha/IFN-gamma) and interleukin 1 alpha (IL-1 alpha)/IFN-gamma enhanced adhesion molecule expression and the adhesion of T cells to synovial cells. Anti-intercellular adhesion molecule 1 blocked adhesion of T cells to TNF alpha/IFN-gamma and IL-1 alpha/IFN-gamma stimulated synovial cells while an antibody to CD61 blocked adhesion to IL-1 alpha/IFN-gamma stimulated cells. CONCLUSIONS: The interaction of leukocytes with adhesion molecules on synovial cells may play a role in recruitment of these cells to an inflammatory site. PMID- 8006885 TI - Utility of needle muscle biopsy in a university rheumatology practice. AB - OBJECTIVE: To evaluate the utility of percutaneous needle muscle biopsy (NMB) as an alternative to open biopsy for the evaluation of patients with myopathy encountered in a university hospital based rheumatology setting. METHODS: Chart review of all patients (n = 30) who underwent NMB at our institution over a 4 year period. Patients were grouped according to clinical outcome. Records of 91 patients who underwent open biopsy during the same period were reviewed for comparison. RESULTS: NMB results either confirmed or added to the prebiopsy diagnostic suspicion in 11 patients and excluded a low prebiopsy suspicion in 13, thus yielding useful clinical information in 24 of 30 patients (80%). Biopsy left the suspected diagnosis unresolved more frequently in patients undergoing NMB compared to patients who had open biopsy during the same time period (6/30 vs 1/91). In the 6 cases unresolved by NMB, subsequent open biopsy added additional information in only 2 of 5 patients. Sensitivity of NMB for inflammatory myopathy was 83% in the 23 patients suspected of having this disease. NMB could be arranged twice as fast as open biopsy, and provided adequate tissue for evaluation in all cases. CONCLUSIONS: Our results suggest that NMB is an effective tool for obtaining useful diagnostic information, particularly pertaining to the presence of an inflammatory myopathy. The convenience, low morbidity, and sensitivity of NMB make it a procedure worthy of wider application by rheumatologists. PMID- 8006886 TI - The longterm effect of pulsed corticosteroids on the efficacy and toxicity of chrysotherapy in rheumatoid arthritis. AB - OBJECTIVE: To follow those patients who participated in a randomized, double blind placebo controlled trial investigating the effect of pulse methylprednisolone treatment in 60 patients with rheumatoid arthritis (RA) starting chrysotherapy. METHODS: Following completion of the original 24-week trial, 47 of the original 60 patients were reexamined between 32 and 67 weeks after completion of the original study. Patients were assessed by a composite clinical score, the Health Assessment Questionnaire (HAQ), erythrocyte sedimentation rate, C-reactive protein and rheumatoid factor levels. RESULTS: At the end of the 24-week trial, the number of patients who responded well to therapy was significantly greater (p < 0.05) in the patients who had received methylprednisolone (17/30) compared with the placebo group (8/30). At the longterm followup assessment, the mean disability score (HAQ) was significantly less (p < 0.05) in patients receiving the initial steroid pulses. No significant difference in drug toxicity or the length of time that patients remained on gold, was observed between the 2 treatment groups. CONCLUSION: Our study supports a beneficial adjunctive role of pulse corticosteroids in patients with RA starting gold therapy. PMID- 8006887 TI - The impact of disease activity, treatment and disease severity on short-term costs of systemic lupus erythematosus. AB - OBJECTIVE: To assess the impact of disease activity, current treatment, and global disease severity (or damage) on short-term direct and indirect costs of systemic lupus erythematosus (SLE). METHODS: 150 patients were evaluated twice, one year apart. Disease activity was assessed by the SLE disease activity index, and ordinal scales were used to evaluate treatment (prednisone = 0, 1 to 20 mg/day, > 20 mg/day, and use of immunosuppressive agents) and global disease severity [renal severity = 0 to 3, central nervous system (CNS) severity = 0 to 2, hematologic severity = 0 to 1]. Costs were assessed with the economic portion of the Health Assessment Questionnaire adapted for Canada. RESULTS: Global disease severity was significantly correlated with both direct (p = 0.0001) and indirect (p = 0.02) costs, and current treatment with indirect costs (p = 0.002). The renal and CNS subscales of the global severity measure predicted direct costs (p < 0.01) and the CNS subscale predicted indirect costs (p = 0.002). Stepwise multivariable models selected the global severity index (p = 0.004) as a predictor of direct costs, and either the treatment index (p = 0.02) or the global severity index (p = 0.02) as a predictor of indirect costs. CONCLUSION: The global disease severity index, particularly the subscales involving the renal and CNS organ systems, and the treatment index are predictors of the short-term costs of SLE. PMID- 8006888 TI - Lyme disease: an infectious and postinfectious syndrome. AB - OBJECTIVE: To determine chronic morbidity and the variables that influence recovery in patients who had been treated for Lyme disease. METHODS: Retrospective evaluation of 215 patients from Westchester County, NY, who fulfilled Centers for Disease Control case definition for Lyme disease, were anti Borrelia antibody positive and were diagnosed and treated at least one year before our examination. RESULTS: Erythema migrans had occurred in 70% of patients, neurological involvement in 29%, objective cardiac problems in 6%, arthralgia in 78% and arthritis in 41%. Patients were seen at a mean of 3.2 years after initial treatment. A history of relapse with major organ involvement had occurred in 28% and a history of reinfection in 18%. Anti-Borrelia antibodies, initially present in all patients, were still positive in 32%. At followup, 82 (38%) patients were asymptomatic and clinically active Lyme disease was found in 19 (9%). Persistent symptoms of arthralgia, arthritis, cardiac or neurologic involvement with or without fatigue were present in 114 (53%) patients. Persistent symptoms correlated with a history of major organ involvement or relapse but not the continued presence of anti-Borrelial antibodies. Thirty-five of the 114 (31%) patients with persistent symptoms had predominantly arthralgia and fatigue. Antibiotic treatment within 4 weeks of disease onset was more likely to result in complete recovery. Children did not significantly differ from adults in disease manifestations or in the frequency of relapse, reinfection or complete recovery. CONCLUSION: Despite recognition and treatment, Lyme disease is associated with significant infectious and postinfectious sequelae. PMID- 8006889 TI - Induction of cyclooxygenase by interleukin 1: comparative study between human synovial cells and chondrocytes. AB - OBJECTIVE: To investigate the regulation of the prostaglandin (PG) synthesis by interleukin 1 (IL-1) in human synovial cells and chondrocytes. METHODS: Both cell types stimulated by human recombinant IL-1 synthesized PGE2, PGF2 alpha and 6 keto-PGF1 alpha. RESULTS: PGE2 was the major PG synthesized. When arachidonic acid was added exogenously at the end of the stimulation, an increase in the prostaglandin synthesis was observed after 6 and 24 h suggesting that cyclooxygenase is the limiting enzyme. Using actinomycin D and cycloheximide, PG synthesis was shown to be protein synthesis dependent. Inhibition of the constitutive cyclooxygenase by aspirin before the IL-1 stimulation confirmed that the increased prostaglandin synthesis was due to a de novo synthesis of cyclooxygenase. CONCLUSION: This enzyme induction by IL-1 was found to be similar in both cell types. PMID- 8006890 TI - The effect of recombinant human interleukin 1 receptor antagonist on the induction phase of antigen induced arthritis in the rabbit. AB - OBJECTIVE: To determine if systemic administration of human interleukin 1 receptor antagonist (IL-1ra) to rabbits during the induction phase of antigen induced arthritis (AIA) could block inflammation and cartilage proteoglycan loss. METHODS: Recombinant human IL-1ra was administered every 6 h to rabbits beginning 1 h before induction of arthritis. Joint swelling was monitored for 72 h and then animals were killed 6 h after the last dose of IL-1ra. Leukocyte accumulation in the joint space and synovial lining was determined and the proteoglycan content and capacity for synthesis was assessed in the articular cartilage of the control and arthritic joints. RESULTS: Administration of IL-1ra had no detectable effect on the induction of arthritis. Swelling proceeded with a similar time course to untreated AIA animals and at 3 days the cellular infiltrate into synovial fluid (SF) was similarly high, the proteoglycan content of SF was also high and cartilage proteoglycan content was depleted. The biosynthesis of proteoglycan in cartilage was also similarly inhibited. No changes were detected in the cartilage and synovium or SF of the contralateral joints of animals receiving IL-1ra. CONCLUSION: IL-1ra given at a dose shown to block synovitis and proteoglycan loss induced by a bolus injection of recombinant IL-1 in rabbits was unable to inhibit the induction of AIA. Our results suggest that the action of IL-1 is not the major factor responsible for the induction of arthritis in this animal model of inflammatory joint disease. PMID- 8006891 TI - Comparative efficacy and toxicity of 10-ethyl-10-deazaaminopterin and methotrexate in a mycobacterial rat arthritis model. AB - OBJECTIVE: To compare the efficacy and toxicity of the newer antifolate 10-ethyl 10-deazaaminopterin (10-EDAM) with methotrexate (MTX) in an animal model of inflammatory arthritis. METHODS: Groups of 8 or 9 female Lewis rats received intraperitoneal (ip) Mycobacterium butyricum to induce arthritis, and then one of the antifolates at either 1.0 mg/kg/day by oral gavage or 0.2 mg/kg/2 days ip until 25 days post-induction. Treatment groups were compared with control arthritic and non-arthritic animals. Efficacy was assessed by changes in weight, paw volume, and paw diameter, as well as maximum arthritis index, plasma albumin and plasma iron levels. Toxicity was documented for all groups. RESULTS: 10-EDAM was as effective as MTX at identical doses in preventing arthritis. 10-EDAM produced less toxicity than MTX at the higher dose used but similar toxicity at the lower dose. CONCLUSIONS: 10-EDAM may provide an alternative antifolate therapy in the clinical management of inflammatory arthritis, and appears to be less toxic than MTX. PMID- 8006892 TI - Effects of a novel azaspirane (SK&F 105685) on arthritic lesions in the adjuvant Lewis rat: attenuation of the inflammatory process and preservation of skeletal integrity. AB - OBJECTIVE: To determine the effects of SK&F 105685 (N,N-dimethyl-8,8-dipropyl-2 azaspiro[4.5] decane-2-propanamine dihydrochloride) on the arthritic lesions in the tibiotarsal joint of adjuvant arthritic (AA) rats. METHODS: Inhibition of hindpaw inflammation was measured by water displacement. The protective effects on joint integrity were determined by measuring radiographic and histological changes and by scanning electron microscopy. RESULTS: Compared to AA control rats, SK&F 105685 suppressed hindpaw edema 64% or 41-54% in AA rats receiving 30 or 20 mg/kg/day, respectively. Radiographic evaluation showed marked decreases in soft tissue swelling and in the severity of skeletal tissue loss at the tibiotarsal joint in both dose groups. Histologically SK&F 105685 markedly attenuated the extent and severity of the inflammatory lesion and preserved the basic integrity of bone and cartilaginous tissues, including the content and distribution of proteoglycans of the articular cartilages. Cellular changes included decreases in the inflammatory infiltrate and in the number of osteoclasts and chondroclasts. Whereas AA control rats exhibited marked to severe loss (41-70%) of skeletal tissue mass, the loss in rats given 30 mg/kg SK&F 105685 was mild (< 20%). Scanning electron microscopy of the talus revealed only slight erosion of the articular cartilage and general preservation of the underlying bone. In contrast, in AA controls, there was marked erosion of the talar articular cartilage and severe loss of subchondral bone. Spleen cells from SK&F 105685 treated rats had a reduced capacity to respond to concanavalin A and contained suppressor cell activity as measured in a coculture assay. CONCLUSION: Our studies show that SK&F 105685 has remarkable protective effects on the joints of AA rats and suggests that it may attenuate the overall inflammatory process and retard the degenerative loss of skeletal tissue in rheumatoid arthritis in humans. PMID- 8006893 TI - Experimental induction of arthritis in rats immunized with Escherichia coli 0:14 lipopolysaccharide. AB - OBJECTIVE: Escherichia coli 0:14 (E. coli 0:14) induces arthritis in rabbits, mice and rats. This study was designed to investigate the effects of lipopolysaccharide (LPS) on the rat arthritis model induced by systemic injections of E. coli 0:14. METHODS: The induction of arthritis in the ankles of rats immunized by subcutaneous injections with heat-killed E. coli 0:14 and its LPS was studied. The appearance and levels of serum IgM rheumatoid factor-like substance (RFLS) was also investigated. The localization of interleukin 1 (IL-1) and LPS in the ankle joints were investigated immunohistochemically. RESULTS: The induction rate of arthritis in rats immunized with LPS was the same as that in rats immunized with E. coli. LPS and IL-1 were detected in synovial cells, infiltrating cells and some cells on pannus in arthritic joints. Anti-LPS IgM levels in rats immunized with E. coli were as high as those in rats immunized with LPS. RFLS levels in rats immunized with LPS increased more gradually than those in rats immunized with E. coli. CONCLUSION: Our findings suggest that LPS induces arthritis resembling rheumatoid arthritis in rats. The detection of IL-1 in synovial cells in conjunction with LPS suggests that local stimulation of IL-1 production may play an important role in the induction of this experimental arthritis. PMID- 8006894 TI - Effect of exercise on 99mTc-DTPA clearance from knees with effusions. AB - OBJECTIVE: To devise and use a method for assessing the effect of dynamic exercise on synovial blood flow in knees with effusions. METHODS: The clearance rate of intraarticular 99mTc-DTPA (diethylene triamine pentaacetic acid) was continuously monitored by a gamma camera during periods of rest or flexion. The rate of 99mTc-DTPA disappearance during a fixed period of exercise which was interposed between 2 rest periods was estimated by extrapolation between the clearance curves for the 2 rest periods. RESULTS: Cycling and walking increased the clearance rate, straight leg raising had no effect, and flexion decreased the clearance rate. CONCLUSION: Our results suggest that some dynamic exercises can increase the rate of synovial blood flow in joints with effusions. This outcome may be beneficial in inflamed joints which are chronically hypoxic due to elevated intraarticular pressure and consequent chronic synovial ischemia. PMID- 8006895 TI - Relative importance of musculoskeletal disorders as a cause of chronic health problems, disability, and health care utilization: findings from the 1990 Ontario Health Survey. AB - OBJECTIVE: Musculoskeletal disorders (MSD) are a leading cause of morbidity in the population, yet their prominence seems to be insufficiently appreciated. We describe the ranking compared with other major body systems of the prevalence of MSD, including arthritis and rheumatism, and back/neck disorders, as a cause of chronic health problems, longterm disability, restricted activity days, consultation with health professionals, and use of both prescription and nonprescription drugs. METHODS: We analyzed data from the 1990 Ontario Health Survey, a stratified random sample of the household dwelling population in Ontario, based on 45,650 individuals aged 16 years and over. RESULTS: MSD ranked first in prevalence as the cause of chronic health problems, longterm disabilities, and consultations with a health professional and ranked 2nd for restricted activity days and use of both prescription and nonprescription drugs. No other body systems ranked invariably within the top 2 ranks for the morbidity indices examined. Even when compared to other major disease groups, arthritis and rheumatism ranked consistently in the top 3 and back/neck disorders also ranked high. MSD were mentioned as a reason for 40% of all chronic conditions, 54% of all longterm disability, 24% of restricted activity days and almost 20% of health care utilization. The impact of MSD was even greater in the 65 and over age group. CONCLUSIONS: MSD have a major role in the health profile of the population. This high burden of illness should be considered in planning health care services and setting research priorities. PMID- 8006896 TI - Socioeconomic risk factors and musculoskeletal disability. AB - INTRODUCTION: Musculoskeletal disorders are the major cause of disability in adults, and increased understanding of the determinants of disability could have important implications for the health of the population. OBJECTIVES: To explore the socioeconomic risk factors associated with the reporting of musculoskeletal disability in the Canadian Health and Activity Limitation Survey, and to investigate whether these associations are unique or are shared by other causes. METHODS: Stepwise logistic regression analyses were used to calculate adjusted odds ratios to compare the risk of disability vs no disability in relation to sociodemographic risk factors (age, sex, marital status, number in household, income, education, employment status) for 4 causes of disability: musculoskeletal, nonmusculoskeletal, arthritis and back disorders. RESULTS: Findings for sociodemographic risk factors, apart from sex are similar for musculoskeletal and nonmusculoskeltal causes of disability. Disability is independently associated with increasing age, not being married, less years of schooling, lower income and not being employed. CONCLUSIONS: Data from a Canadian cross sectional study show that the risk factors associated with musculoskeletal disability are similar to those for other causes of disability. Discussion of the meaning of these associations needs to take into account the broader context of disability as a whole, rather than focussing solely on musculoskeletal disorders. PMID- 8006897 TI - Fibromyalgia syndrome: assessment of the severity of the condition 2 years after diagnosis. AB - OBJECTIVE: To review the outcome of patients with fibromyalgia syndrome (FMS) diagnosed and treated with minimal intervention in community rheumatology practice. METHODS: Forty-four ambulant patients with FMS, first seen in a 2-month period and treated with a simple management program, were identified and reviewed 2 years after diagnosis. A variety of clinical and psychological features were assessed using standard techniques. RESULTS: Forty-seven percent no longer fulfilled Smythe or ACR criteria for FMS. Remission was objectively identified in 24.2% of assessed patients. Significant differences in objective clinical signs, in symptoms, and in self-described disability were found between patients with and without FMS. Regular physical exercise, rather than drug or specific physical therapies, correlated highly with low FMS activity scores. Analysis of mood and coping strategies at the 2-year review showed low correlations with current FMS activity. CONCLUSION: Community FMS has a better prognosis than the literature suggests. Simple intervention may be associated with good outcome in a significant number of patients with FMS. PMID- 8006899 TI - Development of a self-report functional status index for juvenile rheumatoid arthritis. AB - OBJECTIVE: There are few functional indices available for juvenile rheumatoid arthritis (JRA). Our goal was to develop a reliable, valid and responsive self report physical functional status index for individuals with JRA, ages 8-18 years. METHODS: Activity (item) generation by interview of children, parents, teachers, clinicians yielded 280 items. Categories of self-care, domestic, mobility, school, and extracurricular were chosen by clinicians. Twelve clinicians sorted the items into categories. Item reduction was by these clinicians who rated items for common problems in JRA, importance of performance, and potential for change. RESULTS: Ninety-nine items were retained. A separate section was designed for respondents to identify their priority activities. Content validity of the questionnaire, the Juvenile Arthritis Self-Report Index (JASI), was evaluated by 17 different clinicians. One item was added and none eliminated; all rated the index as a credible functional measure for JRA. CONCLUSION: The JASI has been rigorously developed, and has demonstrated content validity. Index validation is being completed. PMID- 8006898 TI - Effects of nutritional supplementation on bone mineral status of children with rheumatic diseases receiving corticosteroid therapy. AB - OBJECTIVE: Because children with rheumatic disease receiving longterm corticosteroids are at high risk for developing osteoporosis, we attempted to determine whether nutritional supplementation would improve bone status in this group of children. METHODS: In a crossover design study, 10 corticosteroid treated children with rheumatic disease and osteoporosis received calcium and vitamin D supplementation for 6 months to determine their effect on bone density. They were then studied for 6 months without added nutrition supplements. The mean age was 13.1 years with a mean duration of disease of 4.2 years. Six patients had juvenile rheumatoid arthritis, 2 had systemic lupus erythematosus and 2 had mixed connective tissue disease. These children obtained a minimum of 1 g of calcium and 400 IU of vitamin D daily from diet and added supplements. Dual photon absorptiometry, laboratory and dietary data were obtained at baseline, 6 months, and one year. RESULTS: Spinal bone density significantly improved with supplementation. Osteocalcin values remained low throughout the study. CONCLUSION: Our results suggest some children with rheumatic disease receiving corticosteroids would benefit from calcium and vitamin D supplementation. PMID- 8006901 TI - Fatal bronchiolitis obliterans in a patient with juvenile rheumatoid arthritis receiving chrysotherapy. AB - Bronchiolitis obliterans has been described in adults with rheumatoid arthritis, particularly in association with D-penicillamine treatment, but to our knowledge has not been reported in juvenile rheumatoid arthritis (JRA). We describe a 12 year-old girl with JRA who developed bronchiolitis obliterans after a 6-month course of intramuscular gold. She presented with severe obstructive airway disease (FEV1, 17% predicted) unresponsive to bronchodilators, without obvious pathology on chest radiograph. Despite aggressive immunosuppressive therapy and eventual lung transplantation, she died 3 1/2 years after her initial diagnosis of JRA. Although rare, bronchiolitis obliterans must be considered in the differential diagnosis of respiratory distress in children with JRA. PMID- 8006900 TI - Budd-Chiari syndrome associated with antiphospholipid antibodies in a child: report of a case and review of the literature. AB - Budd-Chiari syndrome, hypertension, and thrombocytopenia developed in a 6-year old girl as manifestations of primary antiphospholipid antibody syndrome (APS). She improved with systemic corticosteroid and anticoagulation therapy. Anticardiolipin antibodies were found in the patient, her mother and 3 siblings, suggesting the importance of genetic factors. The clinical features of an APS in children is reviewed. PMID- 8006902 TI - Complicated Cogan's syndrome with aortic insufficiency and coronary stenosis. AB - We describe a case of Cogan's syndrome in a 19-year-old woman with tinnitus, deafness, interstitial keratitis, and complicating aortic insufficiency and coronary stenosis. Serological testing revealed IgG and IgA antibodies against Chlamydia trachomatis. In spite of very high antibody titers there was no direct evidence for C. trachomatis in her urogenital smears or in biopsies of her aortic adventitia, and therefore these findings are of uncertain significance. Reconstruction of the aortic valve and bypass surgery for an ostial stenosis of the left coronary artery were necessary. Ten months after starting cyclosporine treatment her course was stable and cochlear implant surgery was successfully performed. PMID- 8006903 TI - The concomitant expression of vasculitis and coagulopathy: synergy for marked tissue ischemia. AB - We describe 4 patients with coagulopathy and vasculitis that demonstrated marked tissue ischemia and necrosis. In the clinical setting of rapid evolution of vascular insufficiency, the possibility of combined vasculopathic processes should be considered. This is especially so in patients with underlying connective tissue disease such as systemic lupus erythematosus or rheumatoid arthritis, in which both vasculitis and antiphospholipid antibodies are frequently present. Treatment of both pathologic processes may be required to prevent progressive tissue ischemia and necrosis. The use of antiplatelet and/or anticoagulation should be given consideration in addition to immunosuppressive agents. PMID- 8006904 TI - Arthritis and iritis after BCG therapy for bladder cancer. AB - A patient with preexisting inactive ankylosing spondylitis experienced a recurrence of back pain and his first episode of acute peripheral arthritis and iritis after a second course of treatment with BCG for bladder cancer. The occurrence of iritis after BCG therapy has not been reported. The recurrence of spondyloarthropathy and the new appearance of iritis may have been part of a generalized enhancement of immunological reactivity produced by the BCG. PMID- 8006905 TI - Wegener's granulomatosis presenting as lower back pain with prostatitis and ureteral obstruction. AB - A 65-year-old man presented with progressive, severe lower back pain, obstructive uropathy, and weight loss. Examination revealed a large, firm prostate, and laboratory studies included an elevated creatinine, erythrocyte sedimentation rate, and prostate specific antigen level. A chest radiograph displayed multiple nodules and a renal ultrasound demonstrated unilateral hydronephrosis. Biopsies of both the prostate and the lung showed necrotizing granulomas consistent with Wegener's granulomatosis, and the patient had positive cytoplasmic antineutrophil cytoplasmic antibodies. He was treated with cyclophosphamide with resolution of all signs and symptoms, and clearing of his radiograph. Our case represents the rare occurrence of Wegener's granulomatosis presenting as prostatitis and ureteral obstruction. PMID- 8006906 TI - Mesalamine therapy in Reiter's syndrome. AB - A patient with chronic Reiter's syndrome (RS) refractory to nonsteroidal antiinflammatory therapy was prescribed mesalamine (Pentasa) therapy for a 4 month trial. Nine months after discontinuing therapy, mesalamine was reintroduced. A pre and posttreatment ileocolonoscopy with distal ileum biopsy was performed. Our patient responded well to mesalamine therapy as measured by improvement in joint count, morning stiffness, and fatigue. Symptoms returned after cessation of therapy. His RS once again went into remission after reintroduction of mesalamine. The pretreatment biopsy revealed inflammatory lesions usually described in the spondyloarthropathies. These lesions improved with resumption of mesalamine therapy. PMID- 8006907 TI - Pelvic pseudotumoral calcium pyrophosphate dihydrate deposition: an ultrastructural study. AB - We analyzed large periarticular calcifications of the hips and pubis in a woman with diffuse primary chondrocalcinosis, symptomatic in the knees. Serial articular and periarticular biopsies were obtained during surgery for osteoporotic hip fracture. Histologic examination showed diffuse nonbirefringent clumps in red alizarin stained cartilage, capsula and tendon. Scanning electron microscopy with microanalysis indicated a calcium/phosphorus atomic ratio of about 1. Transmission electron microscopy, electron diffraction and Raman spectroscopy assessed calcium pyrophosphate dihydrate (CPPD) in cartilage, synovia, capsula, tendon and muscle. The cause of these hard to observe, bulky CPPD periarticular deposits, which resembled basic calcium phosphate on radiography, is still unclear. PMID- 8006908 TI - Do generic health measures have a role in the assessment of RA? PMID- 8006909 TI - Antibodies to dsDNA in drug induced lupus erythematosus. PMID- 8006910 TI - The presence of chronic widespread pain in the general population. PMID- 8006911 TI - Focal radiolucent hepatic lesions in a patient with juvenile rheumatoid arthritis. PMID- 8006912 TI - Prediction of glomerular filtration rate in patients with rheumatoid arthritis: satisfactory performance of Cockroft formula. PMID- 8006913 TI - Optimal titration of ACE inhibitors. PMID- 8006914 TI - Quinapril and hydrochlorothiazide combination for control of hypertension: assessment by factorial design. Quinapril Investigator Group. AB - A factorial design method was applied in this multicentre trial of the angiotensin-converting enzyme inhibitor quinapril hydrochloride (Accupril) in combination with the diuretic hydrochlorothiazide (HCTZ) to assess the additive effects of the combination versus monotherapy, to characterise the dose-response relationship of each drug in the presence of the other and to determine if quinapril would attenuate the hypokalemic effect of HCTZ. Following a two to four week placebo-baseline period, 460 qualifying patients with a DBP > or = 100 mmHg and < or = 115 mmHg were randomised to an eight week double-blind phase with one of 16 parallel treatments: placebo, one of three doses of quinapril monotherapy, one of three doses of HCTZ monotherapy or one of nine possible corresponding combinations of quinapril and HCTZ. Mean reductions in sitting SBP/DBP at trough with combination therapy ranged from 7.8 mmHg/7.2 mmHg to 19.6 mmHg/15.1 mmHg (n = 458). Results of the response surface analyses indicate that the effects of the two drugs were additive and that the maximum antihypertensive effect of quinapril in combination with HCTZ within the doses studied is achieved approximately at a dose of 26 mg quinapril and 25 mg HCTZ. The degree of attenuation of the hypokalemic effect of HCTZ was directly related to the dose of quinapril. At 40 mg quinapril, the HCTZ dose-related decreases of serum potassium were not apparent and overall hypokalemic effects were attenuated by quinapril. Thus, the combination of quinapril and HCTZ given once daily provided additive antihypertensive effects of predictable degrees and the addition of quinapril attenuated the hypokalemic effect of HCTZ. PMID- 8006915 TI - Differences between black and white persons in blood pressure and related biological variables. AB - In societies with several ethnic groups the prevalence of hypertension is abnormally high in black subjects. In addition, blacks are more susceptible to the consequence of high BP. Compared with whites plasma renin is low in blacks independently of age, the level of BP and dietary sodium consumption. No abnormal mineralocorticoid level has ever been consistently reported in blacks to account for their low renin. However potassium intake, prostaglandin and kallikrein excretions are low in blacks and black/white differences exist in the distribution of the restriction fragment length polymorphism at the gene loci for renin. It is hypothesised that the low renin and the propensity of blacks to hypertension result from elevated free cytosolic calcium. Indeed several factors inducing or associated with an increased cytosolic calcium cluster in blacks, e.g. sodium pump inhibition, high intracellular sodium concentration, low plasma ionised calcium, high parathyroid hormone. Furthermore, intensive calcium mobilisation from intracellular stores in response to circulating serum agonists as observed in skin fibroblasts of blacks might be contributive should it occur in all cells including vascular smooth muscle and juxtaglomerular cells. PMID- 8006916 TI - The Bergen Blood Pressure Study. Estimated prevalence of postural hypotension is influenced by the alerting reaction to blood pressure measurement. AB - The prevalence of postural hypotension, defined as a > or = 20 mmHg decline in SBP from the sitting to the standing position, was studied in 430 subjects aged 67.2 +/- 6.8 years (mean +/- SD). Before the subjects assumed the upright position, three sitting measurements were performed. The difference between the first sitting and standing recording revealed a postural hypotension prevalence of 18.9%. However, when the mean of the two last sitting recordings was used as baseline, only 4.9% of the subjects experienced a > or = 20 mmHg drop in SBP on standing. It is well documented that the alerting reaction to conventional sphygmomanometry causes the BP to rise and that BP decreases spontaneously with repeated measurements. When postural hypotension is based on the difference between the first sitting and the standing recording, the change in BP is not caused by the change in posture alone but reflects the effect of repeated measurements and the regression-towards-the-mean-phenomenon as well. Consequently, the prevalence of postural hypotension is overestimated. Repeated baseline recordings are encouraged in the assessment of postural hypotension. PMID- 8006917 TI - Possible mechanism of vascular damage in pre-eclampsia. AB - To clarify the pathophysiological changes of pre-eclampsia, we investigated the injurious effect of sera from women with pre-eclampsia on cultured endothelial cells, vascular smooth muscle cells and fibroblasts. We obtained serum samples from 32 Japanese women, including 10 healthy nonpregnant women, 12 normal pregnant women and 10 women with pre-eclampsia. Cell injury was measured by the release of radiolabelled chromium from the cells into the culture medium. The mean values +/- SD of percentage chromium release from endothelial cells in normal nonpregnant, normal pregnant and pre-eclamptic subjects were 8.5 +/- 2.4, 8.8 +/- 2.1 and 19.7 +/- 3.6%, respectively. Sera from women with pre-eclampsia demonstrated significantly greater endothelial cell injury than did sera from normal pregnant and nonpregnant subjects. However, normal pregnant and pre eclamptic subjects did not differ with respect to both vascular smooth muscle cell injury and fibroblast injury. These results indicate that a serum cytotoxic to endothelial cells is present in pre-eclampsia and that this activity has a cellular specificity for endothelial cells. PMID- 8006918 TI - Prevalence of immunecomplex-associated glomerulonephritis in hypertensive subjects. AB - Glomerulonephritis demonstrable by immunohistochemistry may be present at post mortem in many patients without overt renal diseases. Systematic renal biopsies in severely hypertensive patients have shown a high prevalence of clinically undiagnosed glomerulonephritis. We have examined the kidneys of 423 consecutive subjects who came to post mortem and full-filled criteria for the diagnosis of hypertension. Patients were considered to be hypertensive if this had been clinically documented during life or if the heart weight/body weight ratio was > 0.005 in the absence of known other causes of cardiac hypertrophy. Normotensive controls were selected on the basis of clinically documented normal BP or a heart weight/body weight ratio of < 0.001. Kidneys were examined by immunohistology (PAP technique using human IgA, IgG, IgM antibodies). Excluding cases with liver cirrhosis, only two of the 337 patients with hypertension (= 0.6%) and none of the 49 normotensive patients had mesangial IgA deposits (P = 0.77). This finding argues against the frequent occurrence of latent glomerulonephritis in elderly patients with manifest hypertension. PMID- 8006919 TI - Time course of reduction in left ventricular mass during long-term antihypertensive therapy. AB - Left ventricular mass sometimes decreases during treatment of hypertension but the effects are inconsistent and the response to long-term treatment is unknown. Therefore the long-term effects of antihypertensive therapy on echocardiographically-proven left ventricular hypertrophy (LVH) were prospectively investigated in 117 previously untreated hypertensive patients (mean age 46 +/- 9 years; 15 women and 102 men). Twenty-two patients received 100 mg of gallopamil daily, 24 patients received 200 mg of metoprolol, 35 patients received both 50 mg of atenolol and 20 mg of nifedipine (follow-up five years), 14 patients received 200 mg of acebutol plus 20 mg of nifedipine, and 21 patients received 50 mg of atenolol and 10 mg of enalapril daily (follow-up of four years). For the entire population, there was a significant (P < 0.001) decrease in left ventricular mass index (LVMI; measurements were performed blind by two observers) of 24.5% after one year, with a further continuous and significant (P < 0.001) reduction of 44.1% after five years of treatment. There was a significant (r = 0.61, P < 0.001) correlation between the extent of LVMI before therapy and the percentage of regression of LVMI after five years of treatment. In 82% of the patients, almost complete regression of LVH was achieved. Nevertheless, there was no significant change in ventricular end-diastolic dimension but fractional shortening increased by 16% (P < 0.001). It can be concluded that achieving maximum regression of LVH by antihypertensive therapy in previously untreated hypertensives takes a long time and depends not only on the drug regimen chosen but especially on the duration of treatment and the extent of pretreatment left ventricular mass. PMID- 8006920 TI - Erythrocyte sodium-lithium countertransport: relationship with plasma renin activity, aldosterone and atrial natriuretic peptide in a population study. AB - The objective of this study was to investigate the relationships between erythrocyte Na-Li countertransport, plasma renin activity (PRA), plasma aldosterone and plasma atrial natriuretic peptide (ANP) in a population-based study, in a cross-sectional observation of a randomly selected sample of a male working population, conducted at the Medical Care Center at the Olivetti Factory in Pozzuoli (Naples). One hundred and seventy-nine male employees aged 45.3 +/- 6.8 years (mean +/- SD), all on unrestricted diet and on no pharmacological treatment were studied. Statistical associations between Na-Li countertransport activity and the hormonal factors being studied were investigated, with control for the possible confounding effects of age, BP and sodium intake. Na-Li countertransport was significantly and positively associated with plasma aldosterone concentration (r = 0.228, P < 0.01) but not with PRA or plasma ANP. Men in the highest quartile of the Na-Li countertransport distribution had significantly higher plasma aldosterone levels than men in the other quartiles (P < 0.01) and this difference was independent of age, body mass, PRA, urinary sodium excretion and blood pressure. It is concluded that plasma aldosterone levels are enhanced and disproportionately high relative to plasma renin activity in individuals with high Na-Li countertransport, independently of known potential confounders. PMID- 8006921 TI - Low-Km aldehyde dehydrogenase deficiency does not influence the elevation of blood pressure by alcohol. AB - Increased alcohol consumption causes hypertension and leads to higher death rates by hemorrhagic strokes. About half of the Japanese population have inactive low Km aldehyde dehydrogenase (ALDH2), which metabolizes acetaldehyde to acetic acid at very low concentrations, leading to severe pharmacological effects of aldehyde when drinking alcohol. We determined persons with inactive ALDH2 using a ethanol patch test. All male workers (n + 163), aged from 21 to 62 years in one factory in Japan took part. They were divided into two groups by alcohol consumption (nondrinkers, light drinkers of < 32 ml/l ethanol per day and moderate to heavy drinkers of > or = 32 ml ethanol per day). The prevalence of persons with inactive ALDH2 was 52.1%. The prevalence of moderate to heavy drinkers among persons with inactive ALDH2 was significantly lower than that among those with active ALDH2 (23% and 41%, respectively: P < 0.05). No significant differences of BP were observed between ALDH2 inactive and active groups at the same consumption of alcohol. This study showed a significant relationship between categories of alcohol use and SBP and DBP (P < 0.05, respectively) controlled for age and body mass index. The mechanism by which alcohol use elevates BP is unlikely to be related to the inactive ALDH2. However, inactive ALDH2 may act as a protective factor against hypertension by reducing alcohol consumption. PMID- 8006922 TI - Long-term effects of four fat-modified diets on blood pressure. AB - The purpose of the present study was to examine the effects of four fat-modified diets on BP in 160 middle-aged subjects most of whom had mildly to moderately elevated serum total cholesterol levels and to analyse the relationship of BP to fatty acid composition of serum cholesterol esters. After screening, the subjects (74 men and 85 women) were randomised for the next six months into one of the four experimental diets: control diet (high in saturated fats) (35/14:10:4, indicating 35% of energy from total fat/14% from saturated, 10% from monoenes and 4% from polyenes in the actual diet), AHA (American Heart Association) type diet (32/10:8:8), monoene-enriched diet (34/11:11:5) and low-fat diet (30/12:8:3). Serum total cholesterol decreased significantly during the AHA type diet and monoene-enriched diet in both men and women. No significant changes were found in BP levels in any of the groups in the long-term when both sexes were analysed together but in men the AHA type diet resulted in a significant decline in SBP ( 4.5 -7.9 mmHg, mean +/- SD) and a consistent reduction was also found in DBP ( 2.1 +/- 8.4 mmHg). In contrast, control diet induced a significant rise (+5.5 +/- 14.3 mmHg) in both SBP and DBP (+3.4 +/- 8.4 mmHg) in men. In women, no persistent significant changes in BP levels were observed. An increase in the sum of proportions of myristic (C14:0), palmitic (C16:0) and palmitoleic acids (C16:1) of serum cholesterol esters was associated with the elevation of BP in men of the control group. Furthermore, at baseline, BP had significant positive correlations with C14:0, C16:0 and C16:1 of serum cholesterol esters in the entire study population whereas linoleic acid had an opposite effect on BP even after adjustment for body mass index and age. PMID- 8006923 TI - Effects of selective alfa 1 and beta 1-adrenoreceptor blockade on lipoprotein and carbohydrate metabolism in hypertensive subjects, with special emphasis on insulin sensitivity. AB - The central role of insulin resistance in patients with essential hypertension was the impetus for the present study, in which carbohydrate and lipid metabolism were examined before and after three months treatment with doxazosin (n = 14) and atenolol (n = 15). After completion of a randomised parallel group trial, the study was extended in a subgroup of the patients who continued treatment with doxazosin for a further nine months (n = 18). Insulin sensitivity was measured with the euglycemic hyperinsulinaemic clamp. Blood glucose and plasma insulin were analysed in the fasting state and during an intravenous glucose tolerance test (IVGTT). Lipoprotein fractions were analysed in serum. After three months, SBP and DBP in the standing position decreased to the same extent after the two drugs whereas the decrease in supine SBP did not reach statistical significance in the doxazosin group. Doxazosin, in contrast to atenolol, decreased serum triglycerides (-17%, P < 0.04) by lowering the VLDL and LDL fractions. Serum cholesterol fell after doxazosin (-7%, P < 0.02) but not after atenolol. The effects of doxazosin on serum lipids remained the same during the long-term follow-up. At three months neither drug had significantly affected variables reflecting insulin sensitivity although atenolol tended to decrease the insulin sensitivity index (-17%, P = 0.08). After 12 months the doxazosin group showed a significant increase in the insulin sensitivity index and a significant decrease in both basal plasma insulin and in the late insulin response at IVGTT.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8006924 TI - Quality assurance of medical software. AB - Quality assurance is a topical issue within the software industry, and various methodological solutions aimed at improving software quality have been proposed. Medical software is generally deemed safety-critical and, as such, should be subject to control procedures exceeding those applicable to general-purpose software. The user/purchaser of medical equipment has an important part to play in the drive for higher-quality medical software, and ways in which the user can influence commercial suppliers are outlined. The implications of existing and planned legislation are also discussed. PMID- 8006925 TI - Three-dimensional measurements of skin surface topography by triangulation with a new laser profilometer. AB - The fast measurement of furrows or wrinkles requires the use of a non-contact device. We have chosen a laser detector based on a triangulation principle, using position-sensitive detectors. This apparatus has a sensitivity of about 2-3 microns for a vertical range > 1 mm; this vertical range can reach 8 mm. There is no contact between the detector and the surface and this reduces the measurement time because, while data are being transmitted, there is no decrease in the scanning speed as with earlier methods. We describe the device and its technical characteristics. The limits of use are shown in the measurement of low-amplitude defects (> 3-4 microns) and of wide defects of < or = 8 mm. Examples of software possibilities and practical applications related to skin microrelief, wrinkles and pathological cases, are also described. PMID- 8006926 TI - Calculation of gait parameters direct from force plate readings. AB - Several parameters used in the assessment of pathological gait are normally determined by measurements obtained by means other than from force plate recordings. Methods are presented whereby parameters such as stride length, step length, cadence, single support time, average forward velocity and angle of foot in contact with the force plate are determined directly from force plate recordings of the gait. PMID- 8006927 TI - Glycopeptide resistance in gram-positive bacteria: from black and white to shades of grey. PMID- 8006928 TI - Retrospective study of 108 cases of botulism in Poitiers, France. AB - Botulism, a food-borne toxin-mediated disease caused by Clostridium botulinum is still a common disease, which is most frequent in the rural environment; 108 cases, 66 males and 42 females, average age 32 years, were recorded from 1965 to 1990 in the infectious disease department of the University Hospital of Poitiers (France). In 83% of patients, the food responsible was home-cured ham. Mean incubation time was 3.4 days; digestive symptoms were observed in 93% of cases, ocular symptoms in 92% and urinary tract dysfunction in 22%. A scale of severity was used to classify the patients into those suffering from severe (6), intermediate (50) and mild (52) forms of the disease. Botulinum toxin type B was found in 36 (52%) of 69 blood samples and in 41 (51%) of 81 samples of the suspected food. From 1965 to 1976, 44 patients were treated with both toxoid and heterologous equine serotherapy. Since 1976, 29 patients have been treated with guanidine hydrochloride (35 mg/kg daily) and 35 patients with guanidine hydrochloride plus heterologous serotherapy. All 108 patients recovered without any sequelae. PMID- 8006929 TI - Restriction endonuclease analysis of adenovirus isolates from sporadic and epidemic ocular infections: experience in a clinical laboratory. AB - Adenovirus isolates from 52 patients with ocular infection over a 3-year period were typed by restriction endonuclease analysis in a clinical laboratory. The results indicated that adenovirus type 8 was the most common cause of adenovirus eye infection during this period, being responsible for 42 (81%) of the 52 cases. Of 42 adenovirus type 8 isolates, 22 showed variant patterns by restriction endonuclease analysis and required multiple enzyme digests for identification. These isolates were readily identified by neutralisation tests. PMID- 8006930 TI - Nucleolar accumulation of Semliki Forest virus nucleocapsid C protein: influence of metabolic status, cytoskeleton and receptors. AB - The nucleolar accumulation of Semliki Forest Virus (SFV) C protein was examined as a function of intact microtubules, intact microfilaments and accessible intermediate filaments. The cytoskeletal components do not seem to play a role in directing C protein to the nucleolus but nucleolar accumulation is energy dependent and saturable. This suggests the involvement of some receptor- (or chaperon-) interaction. PMID- 8006931 TI - The role of neuraminidase in haemagglutination and adherence to colon WiDr cells by Bacteroides fragilis. AB - The role of neuraminidase in haemagglutination and adherence to colon WiDr cells by eight strains of Bacteroides fragilis and four strains of oral black-pigmented gram-negative anaerobes was studied. Neuraminidase treatment resulted in a very small increase of haemagglutination by some of the strains but had no effect on adherence to WiDr cells by all bacterial strains tested except one strain of Prevotella intermedia (HG 110). Inhibition of neuraminidase had no effect on haemagglutination or adherence, nor was any correlation found between haemagglutinating ability and neuraminidase activity in the B. fragilis strain. The results indicated that haemagglutination and adherence of B. fragilis to WiDr cells were not mediated by neuraminidase. PMID- 8006932 TI - Consecutive mutations leading to the emergence in vivo of imipenem resistance in a clinical strain of Enterobacter aerogenes. AB - Three consecutive isolates of Enterobacter aerogenes were obtained from the blood cultures of a hospitalised patient who was receiving antibiotic therapy. The initial isolate possessed an inducible cephalosporinase and was susceptible to third-generation cephalosporins. After ceftazidime treatment, a second isolate resistant to this antibiotic and characterised by stable overproduction of the chromosomal beta-lactamase was obtained, and therapy was altered to a new combination which included imipenem. During this course of treatment, a strain of E. aerogenes was isolated that was resistant to virtually all beta-lactam agents including imipenem. Comparison of biotypes and ribotyping profiles indicated that the three isolates were probably derived from a single strain which had undergone several mutations during antibiotic exposure. Examination of outer-membrane protein (OMP) preparations and lipopolysaccharide (LPS) profiles showed that the imipenem-resistant isolate lacked a major OMP and high molecular mass LPS. Furthermore, this isolate displayed reduced permeability to cephaloridine compared with the initial isolate. The introduction of a plasmid carrying a wild type ampD allele prevented cephalosporinase production and restored beta-lactam susceptibility in the imipenem-resistant isolate. It was concluded that stable derepression of class-I beta-lactamase production and reduced permeability are both required for expression of imipenem resistance in E. aerogenes, and that previous exposure to cephalosporins may encourage the emergence of such strains. PMID- 8006934 TI - A scanning electronmicroscopy investigation of the structure of colonies of different morphologies produced by phenotypic switching of Candida albicans. AB - Variant colony formation by Candida albicans has been described and the phenomenon of phenotypic switching has been studied extensively. Whereas the microstructure of non-variant colonies has been investigated by scanning electronmicroscopy (SEM), the relationship between switched variant colonies and microstructure has not been described. The object of this study was to investigate and compared by SEM the microstructure of the normal colony type and five common variant colony types of C. albicans and to determine whether a pattern of dimorphic growth could account for the characteristic colony morphologies. A general relationship between colony type and structure was observed; smooth colonies consisted entirely of blastospores whereas regular, irregular-wrinkled and semi-rough colonies consisted of different proportion of true hyphae and blastospores. Regular extreme-jagged shaped colonies consisted of an almost pure culture of pseudohyphae, and colonies producing aerial hyphae were composed of pseudo- and true hyphae, as well as blastospores. These results show a clear relationship between colony morphology and development of particular cell types. PMID- 8006933 TI - The diagnosis of delayed post-operative endophthalmitis by polymerase chain reaction of bacterial DNA in vitreous samples. AB - Delayed post-operative endophthalmitis is a complication of modern cataract extraction and posterior chamber lens implantation. Propionibacterium acnes has been isolated in a few such cases but the majority are culture-negative, compounding surgical and medical management decisions. A method of detecting bacterial, and specifically P. acnes, DNA by the polymerase chain reaction (PCR) directed at 16S rDNA is reported. Nested PCR with universal eubacterial primers complimentary to regions of 16S rDNA conserved sequences detected 50 fg of bacterial DNA spike in normal vitreous. Nested PCR with P. acnes primers detected 10 fg of DNA. Vitreous samples from 29 patients undergoing vitrectomy for reasons unrelated to infection and 23 samples from 19 patients with delayed post operative endophthalmitis were analysed. Four (14%) of 29 normal individuals and 17 (74%) of 23 delayed cases gave positive results with universal eubacterial primers. None of 29 and eight of 23 samples gave positive results with P. acnes primers. The 14% positive rate with universal primers in non-infected cases may limit their use in delayed post-operative endophthalmitis. PCR detection of bacterial DNA with specific primers from vitreous samples may prove a useful means of diagnosing delayed post-operative endophthalmitis and facilitating management decisions when conventional bacterial culture is negative. PMID- 8006935 TI - A comparison of immunomagnetic separation and direct culture for the isolation of verocytotoxin-producing Escherichia coli O157 from bovine faeces. AB - Enrichment culture (EC) in modified buffered peptone water followed by immunomagnetic separation (IMS) with magnetic beads coated with an antibody against Escherichia coli O157 (Dynabeads anti-E. coli O157; Dynal, Oslo) was compared with direct culture on cefixime rhamnose sorbitol MacConkey agar (CR SMAC) and cefixime tellurite sorbitol MacConkey agar (CT-SMAC) for the isolation of E. coli O157 from bovine faeces. When used to examine bovine faecal suspensions inoculated with 12 different strains of E. coli O157, EC-IMS was c. 100-fold more sensitive for detection of the organism than direct culture on either medium. During monitoring of a dairy herd, E. coli O157 was isolated from 84 (8.2%) of 1024 rectal swabs taken from cattle over a 4-month period; 23 (27.4% of the 84 strains were isolated by both direct culture and IMS (15 of the 23 were isolated on both media, five on CT-SMAC only and three on CR-SMAC only), whereas 61 (72.6%) strains were isolated by IMS only. IMS is a sensitive and simple technique for the isolation of E. coli O157 from bovine faecal samples and should prove useful in elucidating further the epidemiology of this organism. PMID- 8006936 TI - Specific DNA probes to detect Escherichia coli strains producing cytotoxic necrotising factor type 1 or type 2. AB - Cytotoxic necrotising factors type 1 (CNF1) and type 2 (CNF2) are produced by many Escherichia coli strains isolated from man and animals with intestinal or extra-intestinal colibacillosis. In most laboratories, CNF-producing strains are detected by a cell cytotoxicity assay and confirmed with a neutralisation assay or a mouse footpad assay. In this study, we sought to determine whether DNA probes could detect clinical isolates of E. coli producing CNF2 or CNF1, or both, without the need for cell cultures or animal assays. Two internal fragments of the gene encoding CNF2 were used as DNA probes: a 875-bp XhoI-PstI DNA fragment and an adjacent 335-bp PstI-ClaI fragment. A positive response with both DNA probes was associated with CNF2-producing strains, whereas a positive response with only the 335-bp probe was associated with CNF1-producing strains. Results of colony hybridisation experiments with 185 clinical isolates of E. coli demonstrated that these DNA probes detected CNF2-producing strains with a sensitivity and specificity of 100% and CNF1-producing strains with a sensitivity and specificity of 99%. These two DNA probes should greatly facilitate epidemiological studies to assess the importance of CNF-producing strains as agents of diarrhoea and septicaemia. PMID- 8006937 TI - Pre-formed urease activity of Helicobacter pylori as determined by a viable cell count technique--clinical implications. AB - The pre-formed urease activity of three NCTC reference strains and five clinical isolates of Helicobacter pylori was determined at room temperature (21 degrees C) and 37 degrees C by a viable cell count technique with a conventional urea slope test (Christensen's agar) as well as the commercial CLO-test. The urease activity of two gastroduodenal commensals, Proteus mirabilis and Klebsiella pneumoniae, was also tested. H. pylori strains produced positive reactions with viable cell counts of 10(6)-10(8) cfu within 30 min and with counts of 10(3)-10(6) cfu within 2 h. For some strains, smaller numbers of organisms were needed with the CLO-test than with the conventional test, and incubation of the CLO-test strips at 37 degrees C slightly decreased the number of organisms required for positive results. P. mirabilis produced a positive result on urea slopes with an initial inoculum of 10(7)-10(8) cfu at 2 h, but no positive reaction occurred for K. pneumoniae at 12 h, even with an initial inoculum of 10(11) cfu. However, both P. mirabilis and K. pneumoniae gave a positive result after incubation for 24 h with initial inocula of < 10(1) cfu and 10(3)-10(4) cfu respectively. Incubation at 37 degrees C significantly reduced the inoculum size of these organisms required for a positive result after incubation for 4 h when tested with the slopes, but not with the CLO-test. These findings indicate that H. pylori possesses much greater pre-formed urease activity than P. mirabilis and K. pneumoniae. False negative results for clinical detection of H. pylori in gastroduodenal biopsies may be due to small numbers of organisms, especially after treatment with antimicrobial agents, and false positive results may arise from gastroduodenal commensals or contaminants. PMID- 8006938 TI - Mumps vaccines--current status. PMID- 8006939 TI - A comparative study of the aggregation of human, rat and rabbit platelets by members of the Streptococcus sanguis group. AB - Aggregation of platelets by bacteria is a potential factor in the pathogenesis of infective endocarditis. Twenty-five strains from the Streptococcus sanguis group, including 15 recent isolates from cases of endocarditis, were compared for their ability to aggregate human and rat platelets over periods of 15 and 25 min, respectively. In each case, 76% of strains caused aggregation; the median time to onset of aggregation was longer for human platelets (12 min) than for rat platelets (1 min). Strains unable to aggregate human platelets included three from cases of endocarditis. There was no correlation between the ability to aggregate human and rat platelets, although the majority of strains (60%) aggregated both. Tests on representative strains for their ability to aggregate rabbit platelets gave results similar to those for rat platelets, including a median time of 1 min to onset of aggregation. The differences in the ability of individual bacterial strains to aggregate human and animal platelets indicate that caution is needed in extrapolating in-vitro observations to the in-vivo situation. PMID- 8006940 TI - Agglutination of "Streptococcus milleri" by lectins. AB - The agglutination of 218 clinical isolates and three ATCC type strains of "Streptococcus milleri" was tested with 25 different lectins from plants and fungi. An agglutination reaction with one or more lectins was observed with 42 isolates when the cells were untreated. After trypsinisation of the bacteria, 109 strains yielded a positive reaction and after boiling the bacterial cells at pH2, 218 isolates were agglutinated. As an overall result of our experiments with untreated, trypsinised and boiled cells, 17, 37 and 45 different agglutination patterns, respectively, were obtained. The lectins from Datura stramonium, Robinia pseudoacacia and Dolichos biflorus agglutinated isolates belonging only to Lancefield group C, being non-reactive with other isolates. These lectins were also found to be specific for "large colony type" streptococci of group C. The use of lectin agglutination in epidemiological and ecological studies of "S. milleri" is discussed. PMID- 8006941 TI - Differences in the immune responses of mice and sheep to an aromatic-dependent mutant of Salmonella typhimurium. AB - A live mutant aroA Salmonella serotype Typhimurium ovine strain (S25/1) could be cultured from tissues of mice for up to 90 days after oral infection. Following vaccination, high levels of Salmonella-specific serum IgM, IgG and IgA were produced in addition to high levels of specific intestinal IgA. Moreover, there was also evidence of Salmonella-specific cell-mediated immunity in vaccinated mice in the form of strong delayed-type hypersensitivity and the production of interferon-gamma (IFN-tau) by spleen cells stimulated with Salmonella antigen. The aroA strain was also recovered from the mesenteric lymph nodes and most tissues examined from sheep vaccinated by the oral route. Salmonella-specific IgM was detected in the serum; however, specific IgG responses were very low and there was an absence of specific copro-antibody. Although strong Salmonella specific lymphocyte proliferative responses were detected, they did not result in the production of IFN-tau and flow cytometric analysis revealed that the proliferating cells were predominantly B lymphocytes. Despite the absence of strong vaccine-specific immune responses in vaccinated sheep compared with those seen in mice, both mice and sheep were protected against challenge with virulent wild-type strain S25/1. PMID- 8006942 TI - Interactions of intestinal mediators in the mode of action of cholera toxin. AB - Cholera toxin (CT) and prostaglandin E2 (PGE2) increased the synthesis of 3',5' cyclic adenosine monophosphate (cAMP) in rabbit intestinal mucosa, which appeared to be responsible for inducing the release of 5-hydroxytryptamine (5-HT) from enterochromaffin cells into the intestinal lumen. With isolated intestinal cells, CT induced the synthesis of PGE2 more efficiently from epithelial cells than from lamina propria cells; however, the basal amount of this eicosanoid produced by lamina propria cells was approximately six-fold more than that formed by the epithelial cells. The CT-induced stimulation of arachidonate metabolism appeared to be generalised in nature, as PGF2 alpha and leukotrienes were synthesised in addition to PGE2. Injection of dibutyryl cAMP into the intestinal lumen in vivo markedly reduced both basal levels of PGE2, as well as CT-induced levels of PGE2, released into the luminal fluid. Similarly, when biopsy samples of tissue from rabbit intestinal loops, challenged in vivo with dibutyryl cAMP, were washed and incubated in vitro, the amount of PGE2 synthesis remained below basal levels. In contrast, when biopsy samples of normal small intestinal tissue were exposed in vitro to dibutyryl cAMP, PGE2 synthesis increased. Thus, cAMP appeared to down regulate the levels of intestinal eicosanoids in vivo, despite its innate capacity to evoke PGE2 synthesis from mucosal tissue in vitro. Thus, the data indicate that CT-induced mediators exhibit interactive effects that alter their cellular concentrations, that in turn could affect the biological responses. PMID- 8006943 TI - The clinical importance of gram-positive anaerobic cocci isolated at St Bartholomew's Hospital, London, in 1987. AB - The clinical importance of the gram-positive anaerobic cocci (GPAC) isolated in 1987 at St Bartholomew's Hospital, London, is assessed. Of about 800 anaerobic isolates, 209 (27%) were GPAC, of which 67 (32%) were from abscesses and 22 (11%) were in pure growth. Four species comprised 77% of the 168 isolates available for study: Peptostreptococcus magnus (55 isolates, 33%), P. micros (23, 14%), P. asaccharolyticus (24, 14%) P. asaccharolyticus (24, 14%) and P. anaerobius (27, 16%). Different species were associated with different sites, from P. magnus (usually skin-associated sites; normally cultured with aerobes, infrequently with other anaerobes), P. asaccharolyticus (distributed widely) and P. anaerobius (usually genitourinary and gastrointestinal; always below the diaphragm) to P. micros (always deep sites with other anaerobes). P. magnus was isolated from 15 abscesses and was obtained in pure culture from 11 specimens, six of them abscesses developing from infected sebaceous cysts. P. micros was usually isolated from soft tissue abscesses, never from the skin, and with a characteristic mixed flora consisting of "Streptococcus milleri" and anaerobic gram-negative rods. P. heliotrinreducens was a rare isolate from similar specimens. P. asaccharolyticus was cultured from a wide variety of sites, typically mixed with both aerobes and anaerobes, and frequently from abscesses. Most isolates of P. anaerobius came from gastrointestinal or female genitourinary specimens, never from above the diaphragm and rarely from the skin; cultures were usually heavily mixed. Isolates of P. vaginalis and the "bGAL" group made up 11% of str ains and were usally cultured from superficial sites, P. vaginalis often from post-operative wound infections with Staphylococcus aureus.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8006944 TI - The influence of growth medium on serum sensitivity of Bacteroides species. AB - The susceptibility of 12 different Bacteroides strains (representing nine species) to the bactericidal effect of human serum complement was investigated. When grown in nutrient-rich proteose peptone-yeast extract medium, all 12 strains were, to varying degrees, sensitive to serum. However, when grown in Van Tassell and Wilkins's minimal medium, six of the 12 strains became markedly more serum resistant. Five of these six strains became totally resistant to serum when grown in heat-inactivated (56 degrees C, 30 min) sheep serum. By Percoll discontinuous density centrifugation and light microscopy, the ratio of bacteria with large and small capsules was found to vary with the growth medium used. Lipopolysaccharide (LPS) was extracted with aqueous phenol after growth in the three media. Polyacrylamide gel electrophoresis (PAGE) and silver staining of the LPS showed some differences in LPS profiles in all strains tested. Therefore, variation of growth conditions results in alterations of both the expression of surface structures and, in some cases, sensitivity to serum. The biochemical basis for these changes requires further investigation. PMID- 8006945 TI - Fumarate reductase of Helicobacter pylori--an immunogenic protein. AB - An immunogenic protein with an apparent mol. wt of 80 kDa that was recognised by 55% of sera from patients infected with Helicobacter pylori in Western blots was found in butanol extracts of H. pylori membranes. The N-terminal amino-acid sequence of the 80-kDa protein showed 80% identity with the N-terminal sequence of subunit A of the fumarate reductase of Wolinella succinogenes, suggesting the existence of a fumarate reductase in H. pylori. The membrane fraction of H. pylori catalysed succinate oxidation with methylene blue at a specific enzyme activity of 0.06 U/mg of protein. The enzyme was purified by Triton X100 extraction followed by ion-exchange chromatography. The purified enzyme contained an 80-kDa protein which was recognised by rabbit serum raised against subunit A of fumarate reductase of W. succinogenes. A second protein band with a mol. wt of 31 kDa was recognised by rabbit serum raised against subunit B of fumarate reductase of W. succinogenes. Two-dimensional gel electrophoresis demonstrated that the 80- and 31-kDa proteins were subunits of one protein complex. These results indicate that H. pylori contains an enzyme that is very similar to W. succinogenes fumarate reductase. The 80-kDa subunit was recognised in sonicates of all 32 H. pylori strains tested by rabbit antibodies raised against subunit A of fumarate reductase of W. succinogenes, indicating that fumarate reductase is a common protein in H. pylori. The fumarate reductase of H. pylori might enable the bacterium to perform anaerobic respiration in a similar fashion to other anaerobic or facultative bacteria. PMID- 8006946 TI - ATP-sensitive K+ channel opener acts as a potent Cl- channel inhibitor in vascular smooth muscle cells. AB - We describe the activation of a K+ current and inhibition of a Cl- current by a cyanoguanidine activator of ATP-sensitive K+ channels (KATP) in the smooth muscle cell line A10. The efficacy of U83757, an analogue of pinacidil, as an activator of KATP was confirmed in single channel experiments on isolated ventricular myocytes. The effects of U83757 were examined in the clonal smooth muscle cell line A10 using voltage-sensitive dyes and digital fluorescent imaging techniques. Exposure of A10 cells to U83757 (10 nM to 1 microM) produced a rapid membrane hyperpolarization as monitored by the membrane potential-sensitive dye bis-oxonol ([diBAC4(3)], 5 microM). The U83757-induced hyperpolarization was antagonized by glyburide and tetrapropylammonium (TPrA) but not by tetraethlyl-ammonium (TEA) or charybdotoxin (ChTX). The molecular basis of the observed hyperpolarization was studied in whole-cell, voltage-clamp experiments. Exposure of voltage-clamped cells to U83757 (300 nM to 300 microM) produced a hyperpolarizing shift in the zero current potential; however, the hyperpolarizing shift in reversal potential was associated with either an increase or decrease in membrane conductance. In solutions where EK = -82 mV and ECl = 0 mV, the reversal potential of the U83757 sensitive current was approximately -70 mV in those experiments where an increase in membrane conductance was observed. In experiments in which a decrease in conductance was observed, the reversal potential of the U83757-sensitive current was approximately 0 mV, suggesting that U83757 might be acting as a Cl- channel blocker as well as a K+ channel opener. In experiments in which Cl- current activation was specifically brought about by cellular swelling and performed in solutions where Cl- was the major permeant ion, U83757 (300 nM to 300 microM) produced a dose-dependent current inhibition. Taken together these results (i) demonstrate the presence of a K(+)-selective current which is sensitive to KATP channel openers in A10 cells and (ii) indicate that the hyperpolarizing effects of K+ channel openers in vascular smooth muscle may be due to both the inhibition of Cl- currents as well as the activation of a K(+)-selective current. PMID- 8006947 TI - Some effects of short-chain phospholipids and n-alkanes on a transient potassium current (IA) in identified Helix neurons. AB - Many effects of short-chain phospholipids and n-alkanes on the squid axon sodium current (INa) are consistent with mechanisms involving changes in membrane thickness. Here, we suggest that the actions of short-chain phospholipids on an A type potassium current (IA) in two-microelectrode voltage clamped Helix D1 and F77 neurons are incompatible with such simple mechanisms. Diheptanoyl phosphatidylcholine (diC7PC, 0.2 and 0.3 mM) caused substantial (58 and 79%), and in some cases partially reversible, increases in IA amplitude. These were correlated with hyperpolarizing shifts of up to -7 mV in the voltage dependence of current activation. The voltage dependence of steady-state inactivation was also moved in the hyperpolarizing direction. These effects are the opposite of those described for squid INa. 0.5 Saturated n-pentane and saturated n-hexane caused significant (-3 and -6 mV) hyperpolarizing shifts in the voltage dependence of IA inactivation, qualitatively consistent with their effects on squid INa, while the voltage dependence of activation was moved slightly to the left or unchanged. Hydrocarbons had variable effects on peak current amplitude, although saturated n-pentane produced a clear suppression. DiC7PC caused a 25% increase in the time constant of macroscopic IA inactivation (tau b) but 0.5 saturated n-pentane and saturated n-hexane reduced tau b by 40%. The effects of these agents on current-clamped cells were broadly consistent with their opposing actions on tau b--phospholipids tended to reduce excitability and n-alkanes tended to increase it. Possible mechanisms of IA perturbation are discussed. PMID- 8006948 TI - Role of enhanced Na+ entry in the control of Na,K-ATPase gene expression by serum. AB - The role of enhanced Na+ entry in the induction of Na,K-ATPase subunit mRNAs by serum was investigated in a "nontransformed" rat liver cell line, Clone 9. Exposure of cells to 10% calf serum resulted in a 1.5-fold increase in the rate of Na+ entry associated with a transient rise in cell Na+ content (twofold at 15 min) and a sustained 1.15-fold rise in cell K+ content. After 6 hr of exposure to serum mRNA alpha 1 and mRNA beta 1 content increased by 1.8- and 2.6-fold, respectively. In nuclear run-on assays, serum stimulated the transcription of the alpha 1 gene approximately 1.9-fold while the transcription rate of the beta 1 gene remained unchanged. In cells incubated in Na(+)-free medium where NaCl was replaced by choline chloride, the induction of mRNA alpha 1 by serum was fully preserved, whereas the increase in mRNA beta 1 was prevented. An unexpected finding was that incubation of cells in Na(+)-free medium alone for 6 hr increased mRNA alpha 1 but not mRNA beta 1 content. These results indicate that Na,K-ATPase subunit mRNAs are differentially induced by serum, and that the induction of mRNA alpha 1, in contrast to that of mRNA beta 1, is transcriptionally mediated and does not require the presence of Na+ in the extracellular medium. PMID- 8006949 TI - Maxi K+ channels from the apical membranes of rabbit oviduct epithelial cells. AB - Large conductance (approximately 210 pS), K(+)-selective channels were identified in excised, inside-out patches obtained from the apical membranes of both ciliated and nonciliated epithelial cells grown as monolayers from the primary culture of rabbit oviduct. The open probability of channels showing stable gating was increased at positive membrane potentials and was sensitive to the concentration of free calcium ions at the cytosolic surface of the patch ([Ca2+]i). In these respects, the channel resembled "maxi K+ channels" found in a number of other cell types. The distributions of dwelltimes in the open state were most consistently described by two exponential components. Four exponential components were fitted to the distributions of dwelltimes in the closed state. Depolarizations and [Ca2+]i increases had similar effects on the distribution of open dwelltimes, causing increases in the two open time constants (tau o1 and tau o2) and the fraction of events accounted for by the longer component of the distribution. In contrast, calcium ions and voltage had distinct effects on the distribution of closed dwelltimes. While the three shorter closed time constants (tau c1, tau c2 and tau c3) were reduced by depolarizing membrane potentials, increases in [Ca2+]i caused decreases in the longer time constants (tau c3 and tau c4). It is concluded that oviduct large conductance Ca(2+)-activated K+ channels can enter at least two major open states and four closed states. PMID- 8006950 TI - Contribution of a H+ pump in determining the resting potential of neuroblastoma cells. AB - The aim of this work was to examine the effects of changes in external K+ concentration (Ko) around its physiological value, of various K+ channels blockers, including internal Cs+, of vacuolar H(+)-ATPase inhibitors and of the protonophore CCCP on the resting potential and the voltage-dependent K+ current of differentiated neuroblastoma x glioma hybrid NG108-15 cells using the whole cell patch-clamp technique. The results are as follows: (i) under standard conditions (Ko = 5 mM) the membrane potential was -60 +/- 1 mV. It was unchanged when Ko was decreased to 1 mM and was depolarized by 4 +/- 1 mV when Ko was increased to 10 mM. (ii) Internal Cs+ depolarized the membrane by 21 +/- 3 mV. (iii) The internal application of the vacuolar H(+)-ATPase inhibitors N ethylmaleimide (NEM), NO3- and bafilomycin A1 (BFA) depolarized the membrane by 15 +/- 2, 18 +/- 2 and 16 +/- 2 mV, respectively. (iv) When NEM or BFA were added to the internal medium containing Cs+, the membrane was depolarized by 45 +/- 1 and 42 +/- 2 mV, respectively. (v) The external application of CCCP induced a transient depolarization followed by a prolonged hyperpolarization. This hyperpolarization was absent in BFA-treated cells. The voltage-dependent K+ current was increased at negative voltages and decreased at positive voltages by NEM, BFA and CCCP. Taken together, these results suggest that under physiological conditions, the resting potential of NG108-15 neuroblastoma cells is maintained at negative values by both voltage-dependent K+ channels and an electrogenic vacuolar type H(+)-ATPase. PMID- 8006951 TI - Differential developmental fates of the two calcium currents in early embryos of the ascidian Ciona intestinalis. AB - Two voltage-dependent calcium currents have been described in unfertilized eggs of the ascidian Ciona intestinalis: a low threshold, slowly activating current, and a high threshold fast one. According to the classical criteria for classification of calcium currents, they both share some of the features of L like and T-like currents. We have studied these two calcium currents further by measuring their sensitivity to permeant ions, temperature and inhibitors. Both currents were sensitive to relatively high concentrations of nitrendipine, which was a selective blocker of the low threshold channel. The lanthanide ion gadolinium was a potent blocker of the low threshold current, and cadmium preferentially inhibited the high threshold current. The two calcium currents were regulated in a different manner after fertilization. The density of the high threshold current remained relatively constant, while the low threshold current was lost by the time of first cleavage. This loss following fertilization is similar to the loss of a low threshold sodium current in fertilized eggs of the ascidian Boltenia villosa. Block of the cell cycle with various compounds did not prevent loss of the low threshold calcium current. This observation adds weight to the hypothesis that a loss of excitability is a general property of early development. We conclude that fertilization can differentially modulate channel populations before first cleavage. The mechanism by which this occurs in the ascidian embryo has yet to be discovered. PMID- 8006953 TI - Solute transport across the tonoplast of barely mesophyll vacuoles: Mg2+ determines the specificity, and ATP lipophilic amino acids the activity of the amino acid carrier. AB - After stimulation with ATP and in the absence of divalent cations, isolated barely mesophyll vacuoles exhibited massive solute fluxes across the tonoplast, measured either as efflux of endogenous solutes or as uptake of radioactive labeled compounds. Transported solutes were ions (particularly K+, NO3-, Cl-) and amino acids (for example, ala, arg, asp, gln, leu, met). Addition of Mg2+ in excess of added ATP inhibited fluxes of inorganic ions and of positively charged amino acids, but not, or to a smaller extent, those of neutral amino acids. Thus, Mg2+ increased the specificity of the carrier for amino acids such as alanine and glutamine. All ATP-stimulated transport processes were sensitive towards inhibition by lipophilic amino acids, for example by leucine and phenylalanine. After stimulation with sulfhydryl reagents, the inhibitory properties of Mg2+ and lipophilic amino acids were lost. These data concur with the hypothesis of a single transporter which exhibits a channel-like structure with a low degree of substrate selectivity in the absence of Mg2+, and which functions as a neutral amino acid carrier in the presence of Mg2+. PMID- 8006952 TI - ATP-stimulated electrolyte and mucin secretion in the human intestinal goblet cell line HT29-Cl.16E. AB - The response of confluent monolayers of HT29-Cl.16E cells to stimulation by extracellular ATP and ATP analogues was investigated in terms of mucin and electrolyte secretion. Mucin secretion was measured as release of glucosamine labeled macromolecules trapped at the stacking/running gel interface of polyacrylamide gels and electrolyte secretion as short-circuit current (Isc). Luminal ATP stimulated a transient increase in the release of mucins and of Isc corresponding to a secretory Cl- current. Both secretions peaked at 3 to 5 min after addition of ATP. Maximal ATP-stimulated mucin secretion over 15 min was up to 18-fold above control with an apparent ED50 of approximately 40 microM. Maximal peak Isc after stimulation with ATP was approximately 35 microA/cm2 with an apparent ED50 of about 0.4 mM. ATP-dependent Isc was at least in part due to Cl- secretion since removal of Cl- from the medium reduced the peak Isc by 40% and the Isc integrated over 40 min by 80%. The secretory responses were not associated with cell damage as assessed by failure of ethidium bromide to enter into the cells, absence of release of lactate dehydrogenase, maintenance of monolayer conductance, viability, and responses to repeated applications of ATP. The order of efficacy of nucleotide agonists was similar for both processes with ATP > ADP > AMP > or = adenosine. Luminal ATP was much more effective than basolateral addition of this compound. These results suggest involvement of a luminal P2-type receptor which can initiate signaling pathways for granule fusion and mucin release as well as for activation of Cl- channels. P2-receptor stimulated mucin and Isc release was strongly inhibited by a 30 min preincubation with the classical K+ channel blockers quinine (1 mM), quinidine (1 mM), and Ba2+ (3 mM). Experiments with amphotericin B to measure separately the conductance changes of either luminal or basolateral plasma membrane revealed that quinidine did not directly block the ATP-induced basolateral K+ or the luminal anion channels. The quinidine inhibition after preincubation is therefore most easily explained by interference with granule fusion and location of anion channels in granule membranes. Luminal P2 receptors may play a role in intestinal defense mechanisms with both fluid and mucin secretion aiding in the removal of noxious agents from the mucosal surface. PMID- 8006954 TI - Isolation and characterization of membrane potential changes associated with release of calcium from intracellular stores in rat thymic lymphocytes. AB - Membrane potential changes accompanying Ca2+ influx stimulated by release of Ca2+ from intracellular stores (store-regulated Ca2+ uptake) were monitored in BAPTA loaded rat thymic lymphocytes using the fluorescent indicator bis(1,3 diethylthiobarbituric acid)trimethine oxonol. Depletion of [Ca2+]i stores by the application of thapsigargin, ionomycin or cyclopiazonic acid induced a depolarization which was (i) dependent upon BAPTA-loading, (ii) dependent upon extracellular Ca2+, (iii) independent of extracellular Na+ and (iv) abolished by 5 mM extracellular Ni2+. This depolarization was followed by a charybdotoxin sensitive repolarization and subsequent hyperpolarization to values approximating the K+ equilibrium potential, consistent with secondary activation of a K+ conductance. These membrane potential changes temporally correlated with Ca2+ influx from the extracellular medium as measured fluorimetrically with indo-1. The divalent cation permeability sequence was investigated by monitoring the magnitude of the depolarization observed following the addition of 4 mM Ca2+, Mn2+, Ba2+ or Sr2+ to cells pretreated with doses of thapsigargin or ionomycin known to activate the store-regulated calcium uptake pathway. On the basis of these experiments, we conclude that the store-regulated Ca2+ uptake pathway has the following permeability sequence: Ca2+ > Mn2+ >> Ba2+, Sr2+ with Mn2+ displaying significant permeability relative to Ca2+. This pathway is distinguishable from other divalent cation uptake pathways reported in other cells types on the basis of its activation by thapsigargin and its high Mn2+ permeability. PMID- 8006955 TI - Does active transport exist? PMID- 8006957 TI - Effects of membrane potential on just detectable movement in rat skeletal muscle: effects of denervation. AB - The potential, Vt, at which a brief test depolarization first elicited movement was determined using two-microelectrode point voltage clamp. We expected that inactivation of excitation-contraction coupling at conditioning potentials between -60 and 0 mV would shift Vt to more positive potentials, and that fibers would become inactivatable with less conditioning depolarization in EDL than soleus. The curve relating Vt to conditioning potential had a negative slope (which was insensitive to addition of 1 mM cobalt or replacement of calcium with 20 mM CaEGTA) between -60 and -35 mV and a steep positive slope with further depolarization Unexpectedly, fibers became inactivatable with less conditioning depolarization in soleus than in EDL when Vt was measured with 50 msec test pulses. However, the positive shift in Vt became less steep as test pulse duration lengthened in soleus fibers. When Vt obtained with test pulses approaching rheobase (10 msec in EDL and 500 msec in soleus) was compared, EDL fibers became inactive with less conditioning depolarization than soleus fibers. The increase in Vt became steeper with 1 mM cobalt or 20 mM CaEGTA and was shifted to more positive potentials by denervation in soleus fibers. We conclude that inactivation (i) does not strongly influence threshold contractions at conditioning potentials between -60 and -40 mV and (ii) influences Vt between -40 and 0 mV in a manner that depends on test pulse duration. PMID- 8006956 TI - Role of calcium in the modulation of Vicia guard cell potassium channels by abscisic acid: a patch-clamp study. AB - There is evidence for a role of increased cytoplasmic Ca2+ in the stomatal closure induced by abscisic acid (ABA), but two points of controversy remain the subject of vigorous debate--the universality of Ca2+ as a component of the signaling chain, and the source of the increased Ca2+, whether influx across the plasmalemma, or release from internal stores. We have addressed these questions by patch-clamp studies on guard cell protoplasts of Vicia faba, assessing the effects of ABA in the presence and absence of external Ca2+, and of internal Ca2+ buffers to control levels of cytoplasmic Ca2+. We show that ABA-induced reduction of the K+ inward rectifier can occur in the absence of external Ca2+, but is abolished when Ca2+ buffers are present inside the cell. Thus, some minimum level of cytoplasmic Ca2+ is a necessary component of the signaling chain by which ABA decreases the K+ inward rectifier in stomatal guard cells, thus preventing stomatal opening. Release of Ca2+ from internal stores is capable of mediating the response, in the absence of any Ca2+ influx from the extracellular medium. The work also shows that enhancement of the K+ outward rectifier by ABA is Ca2+ independent, and that other signaling mechanisms must be involved. A role for internal pH, as suggested by H.R. Irving, C.A. Gehring and R.W. Parish (Proc. Natl. Acad. Sci. USA 89:1790-1794, 1990) and M.R. Blatt (J. Gen. Physiol. 99:615 644, 1992), is an attractive working hypothesis. PMID- 8006958 TI - Satellite glial cell responses to neuronal firing in the nervous system of Helix pomatia. AB - Patch clamp experiments were conducted on satellite glial cells attached to the cell body of neurons in place within the nervous system of the snail Helix pomatia. The glial cells were studied using cell-attached and whole-cell patch clamp configurations while the underlying neurons were under current or voltage clamp control. The resting potential of the glial cells (-69 mV) was more negative than that of the underlying neurons (-53 mV), due to their high K+ selectivity. Densely packed K+ channels were present, some of which were active at the cell resting potential. Neuronal firing elicited a cumulative depolarization of the glial cells. Large K+ currents flowing from V-clamped neurons depolarized the glial layer by up to 30 mV. The glial depolarization was directly correlated with the size of the neuronal K+ current. The glial cells recovered their resting potential within 2-5 sec. The neuronal depolarization induced a delayed (20-30 sec) and persistent (3-4 min) increase in the glial K+ channel opening probability. Likewise, pulses of K+ (20-50 mM)-rich saline activated the glial channels, unless the underlying neuron was held hyperpolarized. In low Ca(2+)-high Mg2+ saline, neuron depolarization and K(+) rich saline did not activate the glial K+ channels. These data indicate that a calcium-dependent signal released from the neuronal cell body was involved in glial channel regulation. Neuron-induced channel opening may help eliminate the K+ ions flowing from active neurons. PMID- 8006959 TI - The effect of ethanol on lateral and rotational mobility of plasma membrane vesicles isolated from cultured Mar 18.5 hybridoma cells. AB - Intramolecular excimer formation of 1,3-di(1-pyrenyl)propane (Py-3-Py) and fluorescence polarization of 1,6-diphenyl-1,3,5-hexatriene (DPH) were used to evaluate the effect of ethanol on the rate and range of the lateral mobility and the range of the rotational mobility of bulk bilayer structures of the plasma membrane vesicles (ATCC-PMV) isolated from cultured hybridoma cells (ATCC TIB 216). In a concentration-dependent manner, ethanol increased the excimer to monomer fluorescence intensity ratio (I'/I) of Py-3-Py in the ATCC-PMV and decreased the anisotropy (r), limiting anisotropy (r infinity) and order parameter (S) of DPH in the ATCC-PMV. This indicates that ethanol increased both the lateral and rotational mobility of the probes in the ATCC-PMV. Selective quenching of DPH by trinitrophenyl groups was utilized to examine the range of transbilayer asymmetric rotational diffusion of the ATCC-PMV. The anisotropy (r), limiting anisotropy (r infinity) and order parameter (S) of DPH in the inner monolayer were 0.024, 0.032, and 0.069, respectively, greater than calculated for the outer monolayer of the ATCC-PMV. Selective quenching of DPH by trinitrophenyl groups was also used to examine the transbilayer asymmetric effects of ethanol on the range of the rotational mobility of the ATCC-PMV. Ethanol had a greater increasing effect on the range of the rotational mobility of the outer monolayer as compared to the inner monolayer of the ATCC-PMV. It has been proven that ethanol exhibits a selective rather than nonselective fluidizing effect within the transbilayer domains of the ATCC-PMV. PMID- 8006961 TI - Stalling of Escherichia coli RNA polymerase in the +6 to +12 region in vivo is associated with tight binding to consensus promoter elements. AB - Three synthetic promoters, PS1, PS2 and PS3, which differ in their core promoter elements, were studied in vivo and in vitro. Whereas an increased homology score correlates with higher rates of RNA polymerase binding, it does not correlate with activity in vivo. Permanganate probing in vivo reveals that PS1, which exhibits the lowest homology score, is rate-limited during the early phase of promoter-RNA polymerase interactions. By contrast, PS2 and PS3, with higher homology scores, are limited at a late step involving an open DNA region spanning from +6 to +12, indicating a stalling of RNA polymerase. These complexes disappear upon treatment of cells with rifampicin and are replaced by open complexes covering the start site. Because initiated complexes are selectively insensitive to rifampicin action, this confirms that RNA polymerase stalled at +6 to +12 has initiated RNA synthesis. Kinetic studies indicate that the enzyme is released slowly from this position and that this slow release appears to be responsible for the low promoter activity. For PS3, which exhibits the highest homology score and which binds RNA polymerase most efficiently, the release of the stalled complex is particularly slow. PS3 is found to be the weakest of the three promoters in vivo. These results support models in which promoter activity can be determined by various rate limiting steps, including those following the formation of open complexes and even the initiation of RNA synthesis. PMID- 8006960 TI - The Na-K-2Cl cotransporter is in a permanently activated state in cytoplasts from Ehrlich ascites tumor cells. AB - Brief incubation of Ehrlich ascites tumor cells with cytochalasin B causes the formation of blebs in the surface membrane. Gentle homogenization removes the blebs as intact cytoplasts which contain neither mitochondrian or nucleus, nor other cytoplasmic membranous organelles. The Na-K-2Cl cotransporter is present in the cytoplasts in a permanently activated state, whereas the Na-K-2Cl transport system in unperturbed intact cells is silent. Pretreatment of intact cells with cytochalasin B for 1 min stimulates the bumetanide-inhibitable K+ influx approximately fivefold. The influx into purified cytoplasts when expressed per g protein is three- to fourfold higher than the influx into cytochalasin B-treated intact cells. Thus, the membrane vesicles are enriched with the cotransporter, and the cotransporter is present in an activated state. The K influx into cytoplasts is inhibited about 40% by Na-free, Cl-free or bumetanide-containing media and to a similar extent by Fab fragments prepared from antiserum against purified proteins of the cotransporter. The KI for bumetanide was 0.19 +/- 0.06 microM for the cytoplasts as compared to 0.67 +/- 0.11 microM for the intact cells. SDS gel electrophoresis of membrane proteins from the cytoplast membranes compared to the membranes of intact cells shows a reduced number of bands and a majority of bands showing reduced staining, whereas a few bands are stained more intensely. Particularly notable is a band at approximately 80 kD, which is similar to the molecular weight previously reported for the main membrane protein isolated from intact cells using a bumetanide-Sepharose affinity column. An immunoblot of the cytoplast preparation using antibodies against the purified bumetanide binding proteins showed strong immunodetection of the approximately 80 kD protein. PMID- 8006962 TI - Context-dependent effects of upstream A-tracts. Stimulation or inhibition of Escherichia coli promoter function. AB - Phased A-tract sequences were inserted in the upstream region of three synthetic promoters known to encompass different rate-limiting steps within the pathway of RNA polymerase-promoter interaction (Ellinger et al., accompanying paper). Promoter PS1, which is rate-limited in complex formation, was stimulated by A tracts in vivo. Permanganate probing showed that the stimulation is due to an enhanced ability to compete for limiting RNA polymerase in vivo, leading to the increased formation of open complexes. By contrast, promoters PS2 and PS3, which are rate-limited in steps following open complex formation, were inhibited in vivo by A-tracts. Permanganate probing showed that the inhibition was accompanied by an A-tract-dependent accumulation of stalled initial transcribing complexes. A single A-tract was as effective as three. The phasing of the A-tracts with respect to the core promoter sequence was found to be important for promoter function. The position that caused maximal activation at one promoter caused maximal inhibition at another. These results suggest that the same molecular interaction gives rise to both inhibition and activation. This is likely to be due to facilitated RNA polymerase binding in the presence of A-tracts, which stimulates binding-limited promoters but inhibits promoter function in which polymerase escape and promoter clearance is rate limiting. PMID- 8006963 TI - The ribosomal RNA gene region in Acanthamoeba castellanii mitochondrial DNA. A case of evolutionary transfer of introns between mitochondria and plastids? AB - Acanthamoeba castellanii, an amoeboid protozoan, occupies an intriguing position in phylogenetic trees based on nuclear rRNA sequences, branching together with or near (as an outgroup to) green algae and land plants. To gain insight into the organization, expression and evolutionary affiliations of the mtDNA of this non photosynthetic protist, we determined the sequence of a 7778 base-pair region containing the single-copy large subunit (LSU) and small subunit (SSU) rRNA genes (rnl and rns, respectively) of the approximately 40 kilobase-pair A. castellanii mitochondrial genome. We also sequenced the 5'- and 3'-terminal portions of the corresponding LSU and SSU rRNAs. In A. castellanii mtDNA, rnl is flanked both upstream and downstream by a cluster of five tRNA genes, with rns and then cox1 (the cytochrome oxidase subunit 1 gene) following immediately further downstream. These genes are all in the same transcriptional orientation and are separated by only short non-coding spacers. Although rnl and rns are organized in a novel way in A. castellanii mtDNA, their SSU and LSU rRNA products are strikingly similar to their eubacterial homologs in primary sequence, secondary structure and post transcriptional modification. In these characteristics, the A. castellanii mitochondrial rRNAs much more closely resemble their counterparts in land plants than do the corresponding mitochondrial rRNAs in the green alga, Chlamydomonas reinhardtii. Although no intervening sequences have so far been found in the mitochondrial rnl of angiosperms (flowering plants), A. castellanii mitochondrial rnl contains three group I introns, all located within highly conserved regions in the 3'-half of the gene and each possessing a free-standing open reading frame (ORF). The insertion site of one of these introns is identical to that of the single group I intron in the chloroplast rnl of C. reinhardtii, and sequence comparison reveals that these two introns (one mitochondrial, the other chloroplast) are structurally homologous both within the core region and within the ORFs they encode. These observations are indicative of intron movement between mitochondria and chloroplasts, either intracellularly in a photosynthetic, remote common ancestor of A. castellanii and C. reinhardtii or, more recently, as a result of an intercellular exchange of genetic information. PMID- 8006964 TI - Equatorial A-band and I-band X-ray diffraction from relaxed and active fish muscle. Further details of myosin crossbridge behaviour. AB - It has been known for many years that the vertebrate striated muscle A-bands and I-bands both contribute to the observed equatorial X-ray diffraction patterns. Despite this, the observed equatorial patterns, with the exception of the clearly distinct Z-reflection, have often been analysed as coming solely from the A-band, since it has not been possible to separate the observed intensity distribution into individual A-band and I-band contributions. Here we show, for the case of diffraction from the highly ordered muscles in bony fish, that it is possible to separate these contributions to the diffraction patterns from intact muscles and to compute separate electron density maps for the A and I-bands. Difference A band density maps between resting and active muscles are distinctly altered when the I-band contribution is removed from the observed equatorial intensity. Results from resting and fully active fish muscle A-bands are compared and interpreted in terms of myosin crossbridge movement; the observations are consistent with specific crossbridge labelling of actin filaments, with a strong azimuthal component of crossbridge movement towards actin. From electron microscopy of freeze-substituted fish muscle, it is shown that the I-band X-ray diffraction pattern probably arises mainly from the thin filament arrangement immediately adjacent to the Z-band. PMID- 8006965 TI - Refined 2.0 A X-ray crystal structure of the snake venom zinc-endopeptidase adamalysin II. Primary and tertiary structure determination, refinement, molecular structure and comparison with astacin, collagenase and thermolysin. AB - Adamalysin II, alias proteinase II, a 24 kDa zinc-endopeptidase isolated from the snake venom of the Eastern diamondback rattlesnake Crotalus adamanteus, is a prototype of the proteolytic domain of snake venom metalloproteinases and of domains found in mammalian reproductive tract proteins. Its 2.0 A crystal and molecular structure was solved by multiple isomorphous replacement using six heavy-atom derivatives, and was refined to a crystallographic R-value of 0.172. 201 of the 203 amino acid residues of adamalysin II are defined by electron density; only the first two residues are disordered and crystallographically undefined in the crystal structure. Three-quarters of these crystallographic amino acid residue assignments were confirmed by chemical sequencing. In addition, the active-site zinc-ion, a hepta-coordinated calcium ion, a fixed sulphate anion and 173 solvent molecules were localized in the structure. Adamalysin II is an ellipsoidal molecule with a relatively flat active-site cleft separating the "upper" main body from a small "lower" subdomain. The regularly folded N-terminal upper domain consists essentially of a central, highly twisted five-stranded beta-pleated sheet flanked by a long and a short surface located helix on its convex side, and by two long helices, one of which represents the central "active site helix", on its concave side. The lower subdomain, comprising the last 50 residues, is organized in multiple turns, with the chain ending in a long C-terminal helix and an extended segment clamped to the upper domain via a disulphide bridge. The catalytic zinc-ion, located at the bottom of the active site cleft, is almost tetrahedrally co-ordinated by His142, His146 and His152, and a water molecule anchored to an intermediate glutamic acid residue (Glu143), with the three imidazole N epsilon 2 nitrogen atoms 2.1 A and the solvent oxygen atom 2.4 A away from the zinc ion. His142, Glu143 and His146 are part of the long active-site helix, which extends up to Gly149, where it turns sharply away towards His152. The importance of these residues for structure and activity of adamalysin II explains their occurrence in the HEXXHXXGXXH consensus sequence. Asp153, which is strictly conserved in these snake venom and reproductive tract metalloproteinases, is buried in the subdomain and seems to stabilize the hydrophobic active-site basement. Some residues behind, the adamalysin peptide chain folds into a characteristic 1,4-turn (the "Met-turn") containing the conserved Met166, which forms a hydrophobic basement for the three zinc-binding imidazoles.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8006967 TI - The chloride effect in human haemoglobin. A new kind of allosteric mechanism. AB - Chloride reduces the oxygen affinity of mammalian haemoglobin by acting as an allosteric effector that stabilizes the quaternary deoxy (T) structure. Perutz and others showed evidence that it does so by neutralizing electrostatic repulsion by an excess of positive charges in the cavity that runs through the centre of the molecule, but without binding to any specific site. On the basis of this proposal, any amino acid substitutions in the central cavity that halve the number of excess positive charges should halve the chloride effect, neutralization of the excess positive charges should inhibit it and introduction of additional positive charges should enhance it. Charge changes on the surface of the molecule should leave it unaltered. We have tested this proposal by measuring the chloride effects in several abnormal human haemoglobins with replacements of polar residues in the central cavity or on the surface that we happened to come across. They all proved consistent with the proposal. It appears that diffusible electrolytes can modify allosteric equilibria without necessarily binding to any specific site. Our proposal also implies that amino acid substitutions that make the central cavity more electropositive should destabilize the T-structure and therefore increase the oxygen affinity, while substitutions that make it more electronegative should do the reverse. A survey of all substitutions reported in the literature shows that this is true, with a few exceptions due to special stereochemical effects. PMID- 8006966 TI - Two-dimensional NMR studies of selenomethionyl calmodulin. AB - Calmodulin (CaM) is a ubiquitous calcium regulatory protein that can interact with almost 30 different target proteins. The majority of the CaM-binding domains of the target proteins are believed to interact with two hydrophobic surfaces on Ca(2+)-CaM; these two regions are very rich in Met residues. To obtain more information about the role of these residues, we have biosynthetically incorporated selenomethionine (SeMet) in place of the nine Met residues of CaM. Amino acid analysis shows that the SeMet-CaM contains 15% Met and 85% SeMet. SeMet-CaM retains many of the properties of the wild-type protein; it activates the enzyme cyclic nucleotide phosphodiesterase, it binds to phenyl-Sepharose and myosin light chain kinase (MLCK) in a calcium-dependent manner, and it experiences a calcium-dependent band shift during SDS-gel electrophoresis. Moreover, by comparing the natural abundance (1H,13C)-heteronuclear multiple quantum coherence (HMQC) spectra of the calcium, apo and target peptide-bound forms of wild-type CaM and SeMet-CaM, we have found that the two proteins have very similar, if not identical, structures. Thus, the substitution of SeMet for Met does not cause a change in the conformation and function of CaM, in agreement with the results obtained for other proteins. The apo, calcium and target peptide bound forms of SeMet-CaM were subsequently studied by natural abundance (1H,77Se) heteronuclear multiple bond correlation (HMBC) and (1H,13C)-HMQC NMR. Nine well resolved 77Se resonances could be observed. Substitution of SeMet for Met gave rise to the same 1H and 13C chemical shift changes for each individual Met residue, this facilitated making the assignments from known 1H,13C assignments of the Met residues. Some of these assignments were confirmed by studying Met-->Leu mutants of CaM. With the exception of Met76, which always remains solvent exposed, all resonances experienced large 77Se chemical shift changes upon the addition of Ca2+ and the MLCK peptide. The large shift changes indicate that the electron distribution in the SeMet side-chain can be adjusted for the different states of CaM, suggesting that the polarizability of sulfur or selenium may be important for the proper functioning of CaM. This study also shows that the natural abundance (1H,77Se)-HMBC experiment provides a sensitive approach for the study of SeMet proteins. PMID- 8006968 TI - Chloride masks effects of opposing positive charges in Hb A and Hb Hinsdale (beta 139 Asn-->Lys) that can modulate cooperativity as well as oxygen affinity. AB - In the human hemoglobin variant Hb Hinsdale, lysine is substituted for asparagine at position beta 139 (H17), which lies in the water-filled cavity that runs through the center of the molecule. This substitution adds two extra cationic residues to the excess of four cationic residues normally lining this cavity. Moo Penn and colleagues who discovered this hemoglobin, found its oxygen affinity in 0.5 M bis-Tris buffer to be lower than that of Hb A. Their finding conflicted with our prediction that additional cationic groups lining the central cavity would destabilize the T-structure by increased electrostatic repulsion and thereby increase the oxygen affinity. We have, therefore, remeasured the ligand binding properties of Hb Hinsdale. In chloride-free Hepes buffer, Hb Hinsdale has greatly increased oxygen affinity and lower cooperativity than Hb A. A comparison of the properties of Hb A, Hb Hinsdale, Hb Deer Lodge (beta 2 His-->Arg) and Hb Abruzzo (beta 143 His-->Arg) in 0.05 M Hepes versus 0.05 M bis-Tris buffers shows that very low chloride concentrations can significantly alter cooperativity as well as oxygen affinity. The apparent conflict between the findings of Moo-Penn and colleagues and our prediction arises from the enhanced chloride effects exhibited by Hb Hinsdale. On going from 0.05 M Hepes to 0.05 M bis-Tris at pH 7.0, log P50 values for Hb A and Hb Hinsdale are increased by 0.28 and 1.12, respectively. The Bohr effect, the kinetics of oxygen dissociation, the second order rate constant of CO binding and the rate of CO recombination after flash photolysis were also determined for Hb Hinsdale. The enhanced chloride sensitivity of Hb Hinsdale is consistent with the allosteric mechanism of chloride interactions proposed by Perutz et al. in the accompanying paper. PMID- 8006969 TI - Thermodynamics of substrates and reversible inhibitors binding to the active site cleft of human alpha-thrombin. AB - The study of the temperature effect on the binding to the active site of human alpha-thrombin for ten different ligands, i.e. nine peptide substrates and the tight binding inhibitor N alpha -(naphthalene-sulphonyl-glycyl)-4-amidino-DL phenyl-alanine-piperidine (alpha-NAPAP), showed that the enthalpy is constant over the temperature range spanning from 10 to 40 degrees C. It was found that the values of the binding enthalpy are linearly correlated to those of entropy, and that this correlation arises from a real phenomenon of chemical compensation. On the other hand, no compensatory chemical effect was found for the process of thrombin acylation. Additional experiments showed that binding to thrombin of two competitive thrombin inhibitors, i.e. proflavin and p-aminobenzamidine, is characterized by a change in the standard heat capacity change (delta Cp), approximately equal to -1 kcal/mol K. By analogy with model compound transfer studies and protein folding investigations, it is proposed that a burial of a large surface area of non-polar residues, roughly equal to 3000 A2, brings about the observed heat capacity change. Altogether, the observed phenomena of the chemical compensation and heat capacity change, although qualitatively different, are interpreted as expressions of the same property of the enzyme, i.e. the capacity to undergo conformational transitions upon ligation of the catalytic domain. These structural transitions are strictly ligand-linked and could play a central role for setting the rules which regulate the specificity of substrates and inhibitors binding to the catalytic groove of human alpha-thrombin. PMID- 8006971 TI - Crystallization of enzyme IIB of the cellobiose-specific phosphotransferase system of Escherichia coli. AB - Crystals of enzyme IIB of the cellobiose-specific phosphotransferase system have been obtained from 15% polyethylene glycol 4000 using both streak-seeding and macroseeding techniques at 4 degrees. Crystals were grown with the hanging drop method of vapour diffusion. Addition of 2-propanol and benzamidine/HCl proved essential to obtain single crystals suitable for X-ray analysis. The crystals diffract to 1.8 A resolution and have the monoclinic space group P2(1), with cell dimensions a = 53.6 A, b = 31.7 A, c = 60.0 A and beta = 101.7 degrees. From a self-rotation function it seems likely that there are two molecules in the asymmetric unit related by a non-crystallographic 2-fold axis. PMID- 8006972 TI - A myosin from a higher plant has structural similarities to class V myosins. AB - In plant cells, myosin is believed to be the molecular motor responsible for actin-based motility processes such as cytoplasmic streaming and directed vesicle transport. In an effort to characterize plant myosin, a cDNA encoding a myosin heavy chain was isolated from Arabidopsis thaliana. The predicted product of the MYA1 gene is 173 kDa and is structurally similar to the class V myosins. It is composed of the highly-conserved NH2-terminal "head" domain, a putative calmodulin-binding "neck" domain, an alpha-helical coiled-coil domain, and a COOH terminal domain. Northern blot analysis shows that the Arabidopsis MYA1 gene is expressed in all the major plant tissues (flower, leaf, root, and stem). We suggest that the MYA1 myosin may be involved in a general intracellular transport process in plant cells. PMID- 8006970 TI - Crystallization and preliminary X-ray analysis of human alpha-galactosidase A complex. AB - Human alpha-galactosidase A (alpha-D-galactoside galactohydrolase; EC 3.2.1.22), the glycosylated lysosomal enzyme deficient in Fabry disease, has been crystallized as a complex with the inhibitor N-6-aminohexanoyl-alpha-D galactopyranosylamine. The "hanging drop" method of vapor diffusion was used to grow crystals from solutions containing 50 mM sodium phosphate (pH 4.0 to 4.5), 120 to 170 mM ZnCl2 and 8 to 10% polyethylene glycol 3350. X-ray diffraction data collected from these crystals indicate that the crystals belong to the orthorhombic space group C222(1) with cell dimensions of a = 93.8 A, b = 141.1 A and c = 184.4 A. The crystals diffract to a resolution of 3 A and native data have been collected to 3.5 A resolution. Assuming one dimer per asymmetric unit with a total molecular mass of 110 kDa (with oligosaccharide chains), the Matthews' coefficient is Vm = 2.77 A3/dalton corresponding to a solvent content of 55% (v/v). The self-rotation function reveals that a non-crystallographic 2 fold axis relates the subunits of each dimer. PMID- 8006973 TI - Harderian gland ultrastructure of the black sea bottlenose dolphin (Tursiops truncatus ponticus). AB - Examination of the Harderian gland structure of the Black Sea bottlenose dolphin, Tursiops truncatus ponticus, at macroscopic, microscopic, and electron microscopic levels shows significant sexual dimorphism. The epithelial cells of male and female glands are different cell types, capable of producing chemically different products. Secretory cells in both sexes contain secretion granules that produce a secretion consisting mainly of proteins and carbohydrates, but thought to be sex-specific in composition. The female glands also contain lipid secretion granules. It is suggested that in the bottlenose dolphin the Harderian gland functions to produce sexually distinct pheromones and may have other physiological activities, e.g., participating in local immunological or endocrine related reactions. PMID- 8006974 TI - Suppression of rabbit myocardial xanthine dehydrogenase activity by an endogenous compound. AB - Xanthine dehydrogenase (XDH) is an important precursor to the oxygen radical producing enzyme xanthine oxidase (XO). We found that the apparent activity of rabbit myocardial XDH increased from 2 +/- 1 to 50 +/- 3 microU/g (P < 0.05) following extraction of tissue homogenate with butanol. Further studies suggested that the basis for this observation was a high molecular weight compound which consumes the XDH cofactor, NAD+. Addition of myocardial homogenate to exogenous NAD+ resulted in depletion of NAD+ and concomitant formation of an additional compound (peak A). Both NAD+ consumption and peak A formation were abrogated by prior extraction of homogenate with butanol. Separation of myocardial homogenate by Sephadex chromatography revealed a high molecular weight compound which suppressed activity of purified milk XDH but not xanthine oxidase (XO). This activity co-eluted with the ability of myocardial homogenate to consume added NAD+ and form peak A. The NAD(+)-consuming activity was heat and acid-labile. In addition, nicotinamide was both a product and an inhibitor of the NADase activity, consistent with the existence of a previously described myocardial glycohydrolase. Extraction of tissue with butanol may be necessary to detect low levels of XDH activity in vitro. PMID- 8006976 TI - Iron effects on myocardial enzymes depend on redox state. AB - Rapid depression of Ca(2+)-uptake by sarcoplasmic reticulum (SR) vesicles and inhibition of the activity of creatine kinase (CK) and pyruvate kinase (PK) was observed during incubation of enzymes with micromolar concentrations of iron in the presence of adenine nucleotides. This effect of iron was dependent on the redox state of the iron as determined by the redox state of the environment. Redox conditions that generated an Fe2+/Fe3+ ratio close to 1 were most effective in depressing Ca(2+)-uptake by SR vesicles. Redox conditions that decreased the Fe2+/Fe3+ ratio by oxidizing iron were most effective in depressing CK activity while redox conditions that significantly increased the Fe2+/Fe3+ ratio by reducing iron were most effective in depressing PK activity. All iron sensitive enzymes possessed N-etylmaleimide (NEM) sensitive sulphydryl groups that are essential for their activity. The sensitivity to inhibition by NEM increased in the order: PK < Ca(2+)-uptake < CK. Iron initiated depression of CK and PK activities were reversible with dithiothreitol (DTT). This indicated that modification of SH groups was an important step in the mechanism by which iron depressed enzyme activity. Iron initiated depression of Ca(2+)-uptake and of the activity of CK and PK was prevented by not allowing the critical Fe2+/Fe3+ ratio to be reached and by binding of iron with desferroxamine and EDTA. These results, together with data from the literature, led us to suggest that changes in the redox state of cellular micro-environments, inevitably taking place during ischemia and reperfusion, may increase the availability of "low molecular weight iron" and, through changes in the redox state of this iron, selectively initiate reversible depression of several enzymes which contain SH groups essential for their activity. PMID- 8006975 TI - Radioimmunochemical quantification of Gi alpha in right and left ventricles from patients with ischaemic and dilated cardiomyopathy and predominant left ventricular failure. AB - An increase of Gi alpha-related pertussis toxin substrates has been observed in the failing myocardium. In order to quantify the protein expression of Gi alpha directly, we developed a fast radioimmunoassay using the iodinated synthetic peptide 125I-KENLKDCGLF. beta-adrenoceptors were studied with 125I-cyanopindolol binding for comparison. Immunoblot experiments using recombinant G-protein alpha subunits showed that DS4 immunostained the G-protein alpha-subunits with a rank order of potency rGi alpha 1 = rGi alpha 2 > rGo alpha >> rGi alpha 3. The G protein alpha-subunits recognized by DS4 in human ventricular membranes comigrated with rGi alpha 1 and rGi alpha 2. The radioimmunoassay had a sensitivity of 2.5 micrograms/ml transducin alpha with an interassay variation of less than 10%. The non-labelled peptide selectively competed with the myocardial 40 kDa membrane protein for binding to the antiserum DS4. Radioimmunochemical quantification of Gi alpha from cardiac membranes showed that in left ventricular membranes (LV) from dilated cardiomyopathy (DCM), there was an increase of Gi alpha by 138.5% when related to mg protein and 135% when related to 3H-ouabain binding sites as membrane marker. In LV from ischaemic cardiomyopathy (ICM), the increase was smaller (58.4%) when related to mg protein compared to the increase of Gi alpha when related to 3H-ouabain binding sites as membrane marker (155% v NF). In contrast, in the right ventricles (RV) there was no increase of Gi alpha in ICM or DCM. The numbers of beta-adrenoceptors were reduced in RV and LV of both, ICM and DCM. It is concluded that the radioimmunoassay may become an important tool for studying the expression of Gi alpha-protein levels and changes thereof in pathological conditions. The amount of immunodetectable Gi alpha proteins is increased in failing LV due to DCM and ICM but not in RV, while beta adrenoceptor down-regulation occurred in RV and LV in both conditions. These findings might indicate that the liability of the LV but not of RV to express Gi alpha-proteins may be increased in predominant LV heart failure. Alternatively, the underlying mechanism, e.g. sympathetic activation, may be regulated locally in the failing heart producing different changes in adjacent chambers. PMID- 8006977 TI - Effects of adriamycin on ionic currents in single cardiac myocytes of the rabbit. AB - Adriamycin has been widely used as an anticancer drug, but its clinical use is limited by a dose-dependent cardiac toxicity. Proposed mechanisms for the adriamycin-induced cardiomyopathy include increasing the Ca current, inhibiting the Na/Ca exchange and dysfunction of the sarcoplasmic reticulum (SR). Using the whole cell voltage clamp technique in single isolated atrial and ventricular myocytes of the rabbit, we have investigated the effect of adriamycin on various current systems which are related to regulating intracellular Ca concentration: the Ca current, the Na/Ca exchange current and [Ca2+]i-dependent currents (ouabain-induced transient inward current and the inward tail current). Adriamycin, 0.05 mg/ml, increased Ca current (L-type) by 61%. Adriamycin inhibited the inward tail current in a dose-dependent manner between 0.02 and 0.1 mg/ml and when low concentration was used the effect was reversible. Ouabain induced transient inward current was also suppressed by 0.05 mg/ml adriamycin. Na/Ca exchange current which is partly responsible for inducing [Ca2+]i-dependent currents was, however, not affected by adriamycin, suggesting that the effect adriamycin on [Ca2+]i-dependent currents is due to inhibition of SR function. From these results it is suggested that the increase of Ca current and inhibition of SR function cause adriamycin-induced cardiac toxicity: SR dysfunction not only causes a decrease of myocardial contractility, it can also accelerate the Ca overload process which might originate from the increase of Ca current. PMID- 8006978 TI - Compensatory asymmetry in down-regulation and inhibition of the myocardial Ca2+ cycle in congestive heart failure produced in dogs by idiopathic dilated cardiomyopathy and rapid ventricular pacing. AB - In this study we used 2.5% myocardial homogenates to study sarcoplasmic reticulum (SR) activity of the Ca2+ pump and Ca2+ release channel (CRC) from dogs with congestive heart failure produced by either rapid ventricular pacing or idiopathic dilated cardiomyopathy. We used the fluorescent indicator dye and ratiometric spectrofluorometry to monitor Ca2+ uptake while the CRC was open and closed with ryanodine. We confirmed and extended conclusions derived from previous studies of the same dogs using isolated SR. Compared to controls, activities of dogs with either form of CHF were decreased by 36% for the Ca2+ pump (33.7 +/- 7.3 and 21.6 +/- 4.2 nM/s), 78% for the CRC (10.0 +/- 2.8 and 1.4 +/- 1.2 nM/s), 53% for total Ca2+-cycling (53.1 +/- 8.5 and 24.8 +/- 4.4 nM/s), and 17% for net Ca2+ uptake (23.7 +/- 4.0 and 19.6 +/- 4.0 nM/s). In the absence of SR and mitochondrial activity, ionized Ca2+ concentration in myocardial homogenates were 70% abnormally increased in dogs with CHF, probably due to decreased concentration of Ca2+-binding proteins. Comparison of homogenate and isolated SR activities indicated lower-than-normal membrane yields for dogs with CHF. This fractionation artefact previously resulted in up to 50% overestimation of the degree of downregulation of Ca2+-cycling activities in CHF. The CRC activity was found to be decreased due to decreased activity of the Ca2+-ATPase, decreased CRC content, and inhibition. Decreased CRC energy. Maintenance of net Ca2+-pump activity is expected to maintain the amplitude of the myocardial ionized Ca2+ transient whereas downregulation of the CRC and pump are predicted to reduce the total amount of Ca2+ cycled and slow the rise and fall of the Ca2+ transient. PMID- 8006979 TI - Platelet-activating factor and WEB-2086 directly modulate rat cardiomyocyte contractility. AB - In various isolated cardiac tissue preparations the phospholipid mediator platelet-activating factor (PAF, 1-O-hexadecyl-2-acetyl-sn-glycero-3 phosphorylcholine) may elicit a positive, negative or no inotropic response. In the multicellular preparation it is difficult to differentiate and characterize the direct actions of PAF on the myocardium from the effects due to the release of secondary mediators from non-myocyte cell types. Thus in the present study the inotropic effects of PAF (10(-11), 10(-9), 10(-7) M) and a specific PAF receptor antagonist, WEB-2086, PAF receptor antagonist. WEB-2086, on the contractility of enzymatically isolated adult rat cardiomyocytes have been investigated. PAF (10( 7) M) reduced maximum cell shortening by 23% compared to the initial level, delayed excitation contraction coupling, abbreviated the contraction cycle and reduced the maximum rate of cell lengthening during relaxation. Lower concentrations of PAF elicited smaller negative inotropic responses. There was no evidence of a positive inotropic effect of PAF at any concentration tested or at any time after the onset of treatment. Co-treatment with WEB-2086 (10(-5) M) prevented the negative inotropic response to PAF. WEB-2086 alone increased maximum shortening by 16% compared to initial performance, extended the contraction cycle and increased the maximum rates of shortening and lengthening. WEB-2086 had no effect on excitation contraction coupling latency. The selective alteration of contraction parameters induced by PAF and WEB-2086 indicates that, in addition to antagonizing the negative inotropic action of exogenous PAF, WEB 2086 alone enhances contractility. These results demonstrate that PAF has a direct, receptor-mediated negative inotropic effect on adult contractility. These results demonstrate that PAF has a direct, receptor-mediated negative inotropic effect on adult cardiomyocytes. PMID- 8006980 TI - Calcium modulation of single SR potassium channel currents in heart muscle. AB - The modulating effects of Ca2+ on single K+ channel currents in canine heart sarcoplasmic reticulum were studied using a planar lipid bilayer technique. The open-state probability and the unitary open-state current both decreased gradually as the Ca2+ concentration was reduced from pCa 3 to pCa 7.5. Each single-channel I-V curve was ohmic at any pCa: the modulating effect of Ca2+ within this range was voltage independent. The Ca2+ dose-response curves for the conductances and open probabilities were all biphasic in shape for both sides of the channel at the voltages used. However, Ca2+ within the pCa ranges used caused significantly more prominent activation of conductance and gating properties on the cytoplasmic side than it did on the SR luminal side. Furthermore, conductance decreased when cytoplasmic Ca2+ concentrations were greater than pCa 3. The I-V relation in this instance exhibited inward rectification caused by a voltage dependent fast block. This suggests that cardiac SR K+ channel currents may be activated or inhibited through various types of Ca2+ binding sites on and within the channels. PMID- 8006981 TI - Comparative measurement of myocardial ATP and creatine phosphate by two chemical extraction methods and 31P-NMR spectroscopy. AB - Changes in ATP and creatine phosphate levels during early (up to 150 s) global ischaemia were determined in isolated rat hearts by two chemical extraction methods (a conventional direct perchloric acid extraction and a stepwise extraction using alcohol and perchloric acid solutions) and by qualitative 31P NMR. No difference in the ATP level hardly changed up to 40 s of ischaemia when measured by the three methods, and slightly decreased at 150 s of ischaemia. In contrast to ATP, creatine phosphate content in the normally perfused tissue was observed to be higher by the stepwise extraction (68-73 nmol/mg protein) than by direct perchloric acid extraction (55 nmol/mg protein). The creatine phosphate rapidly decreased to about 50% of normal value at 40 s of ischaemia, and the difference in the normal creatine phosphate content using the two chemical methods disappeared with the progression of ischaemia. Thus, the creatine phosphate more rapidly decreased when observed by the stepwise method than by the other two methods in this ischaemic condition. These results suggest that (1) creatine phosphate exists in an undetermined chemical state (perhaps neither in simple soluble form nor in so-called "bound" form) in rat cardiac myocytes, and (2) the stepwise extraction method is useful to measure the content of energy metabolites and to examine the intracellular chemical state in cardiac tissues. PMID- 8006982 TI - Microdynamics of the phospholipid bilayer in cardiomyopathic hamster heart cell membrane. AB - To investigate the microdynamics and the structural architecture of the membrane phospholipid bilayer during the course of cardiomyopathy, membrane fractions were prepared from hearts of cardiomyopathic Syrian hamsters (BIO 14.6) aged 4, 18 and 31 weeks and compared with age-matched control hamsters (F1b). Membrane cholesterol, phospholipids and phospholipid fatty acids were measured by thin layer chromatography, gas-liquid chromatography and high performance liquid chromatography. Microdynamics of the phospholipid bilayer were determined by a nanosecond fluorometer using pulsed excitation of a fluorescent probe, diphenyl hexatriene. At the age of 4 weeks, there was no difference in lipid compositions and microdynamics between the BIO 14.6 and F1b. At the age of 18 weeks, saturated fatty acids, 18:0 and 22:0 increased and 20:0, 20:2 and 32:4 decreased in the BIO 14.6. At the age of 31 weeks, adding to the above changes in phospholipid fatty acids, unsaturated fatty acids 20:4 and 22:6 decreased, moreover membrane phospholipids, especially phosphatidylinositol and phosphatidylethanolamine significantly decreased. The viscosity and the wobbling angle of phospholipid molecules were decreased significantly. We have previously demonstrated that intracellular Ca2+ accumulation might be responsible for the pathogenesis of cardiomyopathy. Thus, we conclude that cardiomyopathic membrane may alter its structure and function with age. These alterations in cell membranes might be involved in the cardiac hypertrophy and dysfunction through impaired Ca2+ handling in cardiomyopathic hamsters. PMID- 8006983 TI - Transsarcolemmal movement of inorganic phosphate in glucose-perfused rat heart: a 31P nuclear magnetic resonance spectroscopic study. AB - Fluxes of orthophosphate (Pi) across the sarcolemma may be important in myocardial metabolism, yet little is known of these in the intact heart. We used 31P NMR spectroscopy to measure net Pi fluxes from changes in the concentrations of Pi, phosphocreatine (PCr), ATP and "total phosphate" ([TP] = [PCr] + 3[ATP] + [Pi]) in the isolated perfused rat heart in response to a change in extracellular [Pi] from 2 mM to 0 mM. [Pi] decreased to 62% of control with a half-time of 6 min, while [TP] decreased with initial rate 20 mM/h, a measure of net Pi efflux. As [PCr] decreased to 83% of control, phosphorylation potential remained constant. Contractile function was unaffected. Reperfusion with 2 mM Pi reversed all changes, causing net Pi influx at 26 mM/h. Analysed according to a model of net Pi flux, these imply a sarcolemmal permeability rate constant of 13 per h. Insulin in the 2 mM Pi perfusion buffer caused a transient decrease in intracellular [Pi] to 59% of control, while [TP] increased, giving a net Pi influx of 12 mM/h and a permeability constant of 12 per h. [PCr] increased by 28% over 34 min. Thus, insulin caused Pi influx by stimulating Pi incorporation into organic phosphates, transiently decreasing intracellular [Pi] and increasing the outside-to-inside [Pi] gradient. The response to 0 mM and 2 mM Pi perfusion was unaffected by insulin. We conclude that Pi fluxes across the sarcolemma are substantial and may have implications for Pi-free tissue perfusion and clinical hypophosphataemia. PMID- 8006984 TI - Modulation of cardiac sarcoplasmic reticulum ryanodine receptor by sphingosine. AB - Excitation contraction (EC) coupling in muscle cells involves the movement of calcium through the calcium release channel of the sarcoplasmic reticulum (SR) membrane known as the ryanodine receptor. We have recently shown that the novel second messenger, sphingosine, can block calcium release from skinned skeletal muscle fibers and from isolated skeletal muscle SR membranes (Sabbadini et al., J Biol Chem 267: 15475-15484, 1992). In this report, we demonstrate that sphingosine also inhibits calcium release from isolated canine cardiac SR membranes containing the ryanodine receptor when release is induced by caffeine, doxorubicin or by calcium. Sphingosine also prevents the augmentation of [3H] ryanodine binding normally produced by caffeine and doxorubicin and exerts noncompetitive inhibition with regard to both releasing agents. Sphingosine significantly reduces in a dose-dependent manner [3H]-ryanodine binding to the high affinity site of the receptor and increases by several-fold the Kd for binding, which is consistent with a blocking action of sphingosine on the ryanodine receptor calcium channel. Sphingosine inhibits the extent of calcium induced calcium release (CICR) and significantly shifts the threshold for CICR so that a higher level of trigger calcium is required to initiate CICR. The sphingosine inhibition of CICR is consistent with the near abolition of calcium dependent [3H]-ryanodine binding. HPLC analysis of cardiac sphingosine content indicates that sphingosine is present in the cardiac cell at moderately high levels (29.4 nmol/g wet wt for the entire cell and approximately 0.4 microM for the cytosol) which are sufficient to produce significant inhibition by sphingosine on calcium release and ryanodine binding. The data suggest that sphingosine acts on the cardiac ryanodine receptor by opposing the physiological stimulus (e.g. trigger calcium entering via the dihydropyridine receptor). We propose that sphingosine is produced by the T-tubule membranes and that sphingosine is released into the protected intracellular environment of the T tubule/SR junction to negatively modulate calcium release. Consequently, it is possible that sphingosine is a physiologically relevant regulator of calcium levels in the heart. PMID- 8006985 TI - Effect of temperature on Ca(2+)-dependent and mechanical modulators of relaxation in mammalian myocardium. AB - Temperature has long been known to affect mammalian cardiac muscle twitch characteristics; duration is prolonged and force is greater at 24 degrees C compared to 37 degrees C. Myocardial relaxation is also influenced by temperature; its time course is governed by a variety of temperature dependent intracellular processes. To investigate the effects of temperature on the interplay between sarcoplasmic reticulum calcium handling and crossbridge cycling as determinants of relaxation time course, we looked at the effects of temperature on load dependence of relaxation (LDoR). Load clamps of amplitude 90%, 80%...10% of peak developed isometric force were recorded at 24 degrees, 30 degrees, and 37 degrees C in rat right ventricular papillary muscles (n = 7), and load dependence of relaxation was analysed. Increasing temperature attenuated LDoR, suggesting there is a decrease in the efficacy of the sarcoplasmic reticulum relative to mechanical determinants of relaxation time course. Therefore, to more directly probe the relative contributions of changes in the [Ca2+]i transient and mechanical determinants of relaxation, we measured T + dF/dt (time to peak +dF/dt) as an indicator of the timing of peak [Ca2+] and tau f (the time constant of the final exponential decay of force from 10% developed force) as an indicator of mechanical kinetics. Both the [Ca2+]i transient and mechanical processes became faster with increasing temperature, as indicated by decreases in T + dF/dt and tau f; however, the ratio T + dF/dt/tau f increased. We interpret the decrease in LDoR and the increase in T + dF/dt/tau f as demonstrating that mechanical kinetics are more sensitive to temperature than is sarcoplasmic reticulum Ca2+ handling. PMID- 8006986 TI - Modification of cardiac membrane adenylate cyclase activity and Gs alpha by NAD and endogenous ADP-ribosyltransferase. AB - The mechanism by which NAD stimulates cardiac adenylate cyclase was investigated. In highly purified canine cardiac sarcolemma, NAD stimulated adenylate cyclase activity in the presence of agents which activate Gs (i.e. 5 mM AlF4-, 10 microM GTP gamma S, 10 microM GppNHp or isoproterenol plus 2 nM GTP gamma S). Furthermore, the EC50 of isoproterenol to stimulate adenylate cyclase was reduced in the presence of NAD. In membranes incubated with [32P]-NAD, AlF4-, 10 microM GTP gamma S or isoproterenol plus 2 nM GTP gamma S produced a selective increase in the radiolabeling of a single 45-kDa protein which was identified as Gs alpha by immunoprecipitation. Cholera toxin catalysed radiolabeling of the same protein. Neutral hydroxylamine released [32P]-ADP-ribose from Gs alpha prelabeled in the presence of AlF4- and [32P]-NAD indicating that an arginine residue on Gs alpha was modified by an endogenous ADP-ribosyltransferase. ADP ribosyltransferase inhibitors, novobiocin, vitamin K1 or 3-aminobenzamide, inhibited AlF4- stimulated ADP-ribosylation of Gs alpha and NAD potentiation of adenylate cyclase with similar efficacies. The activity responsible for NAD potentiation of adenylate cyclase and ADP-ribosylation of Gs alpha was not removed under hypotonic or hypertonic conditions and therefore appears to be tightly membrane bound. Collectively, these observations indicate that canine cardiac sarcolemma possess an ADP-ribosyltransferase which may constitutively catalyse transfer of an ADP-ribose to activated Gs alpha. PMID- 8006987 TI - Gender-specific differences in expression of mRNAs for functional and structural proteins in rat ventricular myocardium. AB - Sex-related differences in predisposition to heart diseases have long been recognized. The molecular and cellular bases for this difference are unknown. In this study we have compared expression of genes for various structural and functional proteins of muscle and interstitial compartments of the myocardium in the adult and neonatal, male and female rat heart. We have also compared cultured cardiac fibroblasts from male and female hearts with regards to gene expression and proliferative capacity. We showed that in the adult rats, the abundance of mRNAs for contractile proteins alpha- and beta-myosin heavy chain (MHC) is higher in the heart of female rats than in that of age-matched male rats. However, the difference in mRNA level for alpha-MHC was more drastic (736%, P < 0.001) than that for beta-MHC (469%, P < 0.001). mRNA levels for sarcomeric actin in the female heart were greater by 79% (P < 0.001). Collagen type I had a significantly higher (303%, P < 0.01) mRNA level in the female heart compared with the male heart. mRNAs for TGF-beta 1, cytoskeletal actin and connexin 43 were also higher (150%, P < 0.01; 130%, P < 0.01, and 150%, P < 0.01, respectively) in the female heart compared with age-matched male heart. There were no significant sex-related differences at the mRNA levels for the above proteins in ventricular tissue from neonatal male and female littermates. At the cellular level, cardiac fibroblasts obtained from adult and neonatal hearts of both sexes were comparable with respect to the abundance of mRNAs for collagen type I, TGF-beta 1 or cytoskeletal actin. However, DNA synthesis, as measured by [3H]thymidine incorporation, was higher (328%, P < 0.01) in cells from adult female heart compared with that in cells from adult male rat heart. This difference was even more pronounced in cardiac fibroblasts obtained from newborn female rats (933%, P < 0.001) compared with that in cells obtained from newborn male rat hearts. Together, these findings show that there are sex-related differences in gene expression for most major proteins in heart tissue and that this phenomenon is associated with the post-pubertal period. These findings further suggest that sex-related differential gene expression and DNA synthesis in cardiac cells are due to the regulatory effects of male- and female-specific hormones. PMID- 8006988 TI - Single-strand regions of poly(G) act as templates for oligo(C) synthesis. AB - Oligonucleotide primers consisting of a sequence of four or more deoxycytidylate residues terminated by a single ribocytidylate residue are extended by reaction with cytidine 5'-phosphoro(2-methyl)imidazolide using polyguanylic acid as a template. The efficiency of the reaction decreases as the length of the primer increases. The reaction does not seem to depend on the dissociation of poly(G) tetrahelices but uses as templates single-stranded segments that are already present in enzymatically synthesized polyguanylic acid. PMID- 8006990 TI - Evolution of the primate cytochrome c oxidase subunit II gene. AB - We examined the nucleotide and amino acid sequence variation of the cytochrome c oxidase subunit II (COII) gene from 25 primates (4 hominoids, 8 Old World monkeys, 2 New World monkeys, 2 tarsiers, 7 lemuriforms, 2 lorisiforms). Marginal support was found for three phylogenetic conclusions: (1) sister-group relationship between tarsiers and a monkey/ape clade, (2) placement of the aye aye (Daubentonia) sister to all other strepsirhine primates, and (3) rejection of a sister-group relationship of dwarf lemurs (i.e., Cheirogaleus) with lorisiform primates. Stronger support was found for a sister-group relationship between the ring-tail lemur (Lemur catta) and the gentle lemurs (Hapalemur). In congruence with previous studies on COII, we found that the monkeys and apes have undergone a nearly two-fold increase in the rate of amino acid replacement relative to other primates. Although functionally important amino acids are generally conserved among all primates, the acceleration in amino acid replacements in higher primates is associated with increased variation in the amino terminal end of the protein. Additionally, the replacement of two carboxyl-bearing residues (glutamate and aspartate) at positions 114 and 115 may provide a partial explanation for the poor enzyme kinetics in cross-reactions between the cytochromes c and cytochrome c oxidases of higher primates and other mammals. PMID- 8006989 TI - Polycytidylate and poly(7-deazaguanylate): a pair of complementary templates. AB - We have studied the template-directed oligomerization on polycytidylic acid of the 5'-phosphoro(2-methyl)imidazolides of a number of analogues of guanosine. None of the analogues reacted as efficiently as the original guanosine compound, and only the 7-deazaguanosine analogue gives a detectable yield of oligomers. Similar results are described for a reaction involving the intramolecular template-directed elongation of a short oligocytidylate primer. Oligocytidylates containing five or more cytidylate residues are extended on the single-stranded regions of poly(G). In the present study we show that these oligocytidylates are extended efficiently by reaction with cytidine-5'-phosphoro(2-methyl)imidazolide on a poly(7-deazaguanylic acid) template. The products are considerably longer than those obtained using a polyguanylic acid template. We believe that the formation of a tetrahelix inhibits the latter reaction, while poly(7 deazaguanylate) does not aggregate and, therefore, acts as a more efficient template. This work identifies for the first time a pair of homopolymers each of which facilitates the template-directed elongation of the other. PMID- 8006991 TI - Intron-containing globin genes in the insect Chironomus thummi. AB - All previously reported chironomid globin genes are intronless, suggesting that the ancestral chironomid globin gene was also intronless. In this study, the coding regions of the closely linked Chironomus thummi globin (Gbs) II beta and IX genes are shown to be interrupted by noncoding DNA bounded by a 5'-GT and a 3' AG. Both genes have appropriately placed transcription and translation signals. Polymerase chain reactions on genomic DNA with oligonucleotides flanking and within the putative Gb II beta intron generated products the size predicted for a gene with a 64-nucleotide intron, and sequencing of a cloned PCR fragment also revealed the intron. A partial-length Gb II beta cDNA sequence exactly matches that of the Gb II beta coding regions. We conclude that the intron-containing chironomid globin genes are functional. Regions of the Gb II beta and IX genes spanning the introns are more similar (86%) than the exons themselves (72% similarity), possibly due to partial gene correction. Surprisingly, Gb II beta and IX gene homologues in C. tentans are intronless. If the common ancestor of chironomid globin genes was not intronless, introns were lost in at least three C. thummi globin-gene lineages, and more recently by Gb II beta and Gb IX genes in C. tentans. If, as previously believed, the ancestral chironomid globin gene was intronless, the ancestral chironomid globin gene was intronless, then an intron was recently acquired in only one C. thummi globin sublineage. These alternatives are discussed. PMID- 8006992 TI - Phylogeny and physiology of Drosophila opsins. AB - Phylogenetic and physiological methods were used to study the evolution of the opsin gene family in Drosophila. A phylogeny based on DNA sequences from 13 opsin genes including representatives from the two major subgenera of Drosophila shows six major, well-supported clades: The "blue opsin" clade includes all of the Rh1 and Rh2 genes and is separated into two distinct subclades of Rh1 sequences and Rh2 sequences; the ultraviolet opsin clade includes all Rh3 and Rh4 genes and bifurcates into separate Rh3 and Rh4 clades. The duplications that generated this gene family most likely took place before the evolution of the subgenera Drosophila and Sophophora and their component species groups. Numerous changes have occurred in these genes since the duplications, including the loss and/or gain of introns in the different genes and even within the Rh1 and Rh4 clades. Despite these changes, the spectral sensitivity of each of the opsins has remained remarkably fixed in a sample of four species representing two species groups in each of the two subgenera. All of the strains that were investigated had R1-6 (Rh1) spectral sensitivity curves that peaked at or near 480 nm, R7 (Rh3 and Rh4) peaks in the ultraviolet range, and ocellar (Rh2) peaks near 420 nm. Each of the four gene clades on the phylogeny exhibits very conservative patterns of amino acid replacement in domains of the protein thought to influence spectral sensitivity, reflecting strong constraints on the spectrum of light visible to Drosophila. PMID- 8006993 TI - Interspecific comparison of Drosophila serendipity delta and beta: multimodular structure of these C2H2 zinc finger proteins. AB - The Drosophila serendipity (sry) beta and delta genes, which resulted from a gene duplication event, provide an interesting model for the evolutionary diversification in structure and function of C2H2 zinc finger proteins. We examined here the divergence of the sry beta and delta proteins over an estimated period of 45 million years by comparing their predicted sequences in D. melanogaster, D. pseudoobscura, and D. subobscura. Between orthologs, i.e., pairs of either sry beta or sry delta, the NH2-proximal region delineated by pairs of C X2-C motifs and the DNA-binding finger domain are highly conserved. Sequence conservation operates over the entire finger domain, including the links separating adjacent fingers, even though each has a unique sequence different from the widespread TGEKP motif. In contrast, the sequence of the central acidic region has extensively diverged and differs between species in the number of amino acids, probably because of slippage-driven mutations. The NH2-terminal region and fingers 1, 5, and 6 differentiate the sry beta and delta proteins while zinc fingers 2, 3, and 4 are virtually identical in these two paralogs. A nuclear localization signal of the SV40T antigen type, preceded by a potential CKII phosphorylation regulatory site, is conserved in sry delta but not found in sry beta. The interspecific conserved regions correlate well with the positions of zygotic lethal mutations in the D. melanogaster sry delta protein. Furthermore, P-element transformation experiments show that a transgenic copy of the D. pseudoobscura sry delta gene rescues the sry delta mutant phenotype. Convergence of genetic and structural data on the sry proteins supports a multimodular function and mode of evolution of these C2H2 finger proteins. PMID- 8006994 TI - Structural rearrangements, including parallel inversions, within the chloroplast genome of Anemone and related genera. AB - Chloroplast DNA cleavage sites for 10 restriction enzymes were mapped for 46 species representing all sections of Anemone, four closely related genera (Clematis, Pulsatilla, Hepatica, and Knowltonia), and three more distantly related outgroups (Caltha, Ranunculus, and Adonis). Comparison of the maps revealed that the chloroplast genomes of Anemone and related genera have sustained an unusual number and variety of rearrangements. A single inversion of a 42-kb segment was found in the large single-copy region of Adonis aestivalis. Two types of rearrangements were found in the chloroplast genome of Clematis, Anemone, Pulsatilla, Hepatica, and Knowltonia: An approximately 4-kb expansion of the inverted repeat and four inversions within the large single-copy region. These rearrangements support the monophyletic status of these genera, clearly separating them from Caltha, Ranunculus, and Adonis. Two further inversions were found in two Clematis species and three Anemone species. While appearing to support a monophyletic grouping for these taxa, these two inversions conflict with data from both chloroplast restriction sites and morphology and are better interpreted as having occurred twice independently. These are the first two documented cases of homoplastic inversions in chloroplast DNA. Finally, the second intron of the chloroplast rps 12 gene was shown to have been lost in the common ancestor of the same three Anemone species that feature the two homoplastic inversions. PMID- 8006996 TI - Unbiased estimates of the number of nucleotide substitutions when substitution rate varies among different sites. AB - When the number of nucleotides examined is relatively small, the estimators of nucleotide substitutions between DNA sequences often introduce systematic error even if the data used fit the mathematical model underlying the estimation formula. The systematic error of this kind is especially large for models that allow variation in substitution rate among different sites. In the present paper we present a number of formulas that produce virtually bias-free estimates of evolutionary distances for these models. PMID- 8006997 TI - Estimating errors and confidence intervals for branch lengths in phylogenetic trees by a bootstrap approach. AB - A method, based on the bootstrap procedure, is proposed for the estimation of branch-length errors and confidence intervals in a phylogenetic tree for which equal rates of substitution among lineages do not necessarily hold. The method can be used to test whether an estimated internodal distance is significantly greater than zero. In the application of the method, any estimator of genetic distances, as well as any tree reconstruction procedure (based on distance matrices), can be used. Also the method is not limited by the number of species involved in the phylogenetic tree. An example of the application of the method in the reconstruction of the phylogenetic tree for the four hominoid species--human, chimpanzee, gorilla, and orangutan--is shown. PMID- 8006995 TI - The cytochrome b region in the mitochondrial DNA of the ant Tetraponera rufoniger: sequence divergence in Hymenoptera may be associated with nucleotide content. AB - Polymerase chain reaction (PCR) followed by sequencing of single-stranded DNA yielded sequence information from the cytochrome b (cyt b) region in mitochondrial DNA from the ant Tetraponera rufoniger. Compared with the cyt b genes from Apis mellifera, Drosophila melanogaster, and D. yakuba, the overall A+T content (A+T%) of that of T. rufoniger is lower (69.9% vs 80.7%, 74.2%, and 73.9%, respectively) than those of the other three. The codon usage in the cyt b gene of T. rufoniger is biased although not as much as in A. mellifera, D. melanogaster, and D. yakuba; T. rufoniger has eight unused codons whereas D. melanogaster, D. yakuba, and A. mellifera have 21, 20, and 23, respectively. The inferred cyt b polypeptide chain (PPC) of T. rufoniger has diverged at least as much from a common ancestor with D. yakuba as has that of A. mellifera (approximately 3.5 vs approximately 2.9). Despite the lower A+T%, the relative frequencies of amino acids in the cyt b PPC of T. rufoniger are significantly (P < 0.05) associated with the content of adenine and thymine (A+T%) and size of codon families. The mitochondrially located cytochrome oxidase subunit II genes (CO-II) of endopterygote insects have significantly higher average A+T% (approximately 75%) than those of exopterygous (approximately 69%) and paleopterous (approximately 69%) insects. The increase in A+T% of endopterygote insects occurred in Upper Carboniferous and coincided with a significant acceleration of PPC divergence. However, acceleration of PPC divergence is not significantly correlated with the increase of the A+T% (P > 0.1). The high A+T%, the biased codon usage, and the increased PPC divergence of Hymenoptera can in that respect most easily be explained by directional mutation pressure which began in the Upper Carboniferous and still occurs in most members of the order. Given the roughly identical A+T% of the cyt b and CO-II genes from the other insects whose DNA sequences are known (A. mellifera, D. melanogaster, and D. yakuba), it seems most likely that the A+T% of T. rufoniger declined secondarily within the last 100 Myr as a result of a reduced directional mutation pressure. PMID- 8006998 TI - Monte Carlo simulation in phylogenies: an application to test the constancy of evolutionary rates. AB - Monte Carlo simulation has commonly been used in phylogenetic studies to test different tree-reconstruction methods, and consequently, its application for testing evolutionary models can be considered as a natural extension of this usage. Repetitive simulation of a given evolutionary process, under the restrictions imposed by the model to be tested, along a determinate tree topology allow the estimate of probability distributions for the desired parameters. Next, the phylogenetic tree can be reconstructed again without the constraints of the model, and the parameter of interest, derived from this tree, can be compared to the corresponding probability distribution derived from the restricted, simulated trees. As an example we have used Monte Carlo simulation to test the constancy of evolutionary rates in a set of cytochrome-c protein sequences. PMID- 8006999 TI - Genomic alignment. AB - As sequencing techniques become increasingly efficient, the average length of a sequence is bound to grow. Traditional sequence-comparison algorithms can either compare DNA or protein, but not a mixture, which is actually a common situation. Most obtained DNA sequences contain coding regions, and it is more reliable to compare the coding regions as protein than just as DNA. A heuristic algorithm is presented that can compare DNA with both coding and noncoding regions, but that also can compare multiple reading frames and determine which exons are homologous. A program, GenA1 (Genomic Alignment), was developed that implements the algorithm. Its use is demonstrated on two retroviruses. PMID- 8007000 TI - The evolutionary origin of red algae as deduced from the nuclear genes encoding cytosolic and chloroplast glyceraldehyde-3-phosphate dehydrogenases from Chondrus crispus. AB - Algae are a heterogeneous group of photosynthetic eukaryotes traditionally separated into three major subdivisions: rhodophytes, chlorophytes, and chromophytes. The evolutionary origin of rhodophytes or red algae and their links to other photosynthetic and nonphotosynthetic eukaryotes have been a matter of much controversy and speculation. Here we present the first cDNAs of nuclear protein genes from red algae: Those encoding cytosolic and chloroplast glyceraldehyde-3-phosphate dehydrogenases (GAPDH) from Chondrus crispus. A phylogenetic analysis including GAPDH gene sequences from a number of eukaryotic taxa, cyanobacteria, and purple bacteria suggests that chloroplasts and rhodoplasts together form a monophyletic group of cyanobacterial descent and that rhodophytes separated from chlorophytes at about the same time as animals and fungi. The composite GAPDH tree further demonstrates that chloroplast and cytosolic GAPDH genes are closely related to their homologs in cyanobacteria and purple bacteria, respectively, the presumptive ancestors of chloroplasts and mitochondria, thereby firmly establishing the endosymbiotic origin of these nuclear genes and their fixation in eukaryotic cells before the rhodophyte/chlorophyte separation. The present data are in conflict with phylogenetic inferences based on plastid-encoded rbcL sequences supporting a polyphyletic origin of rhodoplasts and chloroplasts. Comparison of rbcL to GAPDH phylogenies suggests that rbcL trees may be misleading because they are composed of branches representing ancient duplicated (paralogous) genes. PMID- 8007001 TI - Codon usage patterns suggest independent evolution of two catabolic operons on toluene-degradative plasmid TOL pWW0 of Pseudomonas putida. AB - TOL plasmid pWW0 of Pseudomonas putida encodes a set of enzymes responsible for the degradation of toluene. The structural genes for these catobolic enzymes are clustered into two operons--namely, the xy/CMAB and xy/XYZLTEGFJQKIH operons. We examined the codon usage patterns of these catabolic genes by measuring the codon usage distances between pairs of these catabolic genes. The codon-usage distance, d, between gene 1 and gene 2 was defined as d = [sigma(pj-qj)2]1/2, are the frequencies of the j-th codon in gene 1 and 2, respectively, j being any one of the 64 possible codons. We found that the genes in the same operon exhibit similar codon-usage patterns while genes in the different operons exhibit different codon bias. This observation suggests that genes in the same operon have coevolved, and that the ancestors of the xy/CMAB and xy/XYZLTEGFJQKIH operons evolved in different organisms. PMID- 8007002 TI - The sequence and expression pattern of the Calliphora erythrocephala yolk protein A and B genes. AB - The yolk protein genes (yps) are expressed in a temporal, tissue- and sex specific fashion in Drosophila melanogaster. Here we report the sequence of two related genes in Calliphora erythrocephala. The predicted Calliphora yolk protein (YP) sequences are well conserved, especially at the C-terminal end when compared to those of D. melanogaster and Ceratitis capitata. Database searches with the Calliphora yolk protein B (CeYPB) sequence identify the vertebrate lipase similarity reported for the YPs of Drosophila and Ceratitis. Moreover, sequences with identity to divalent ion-binding sites were observed, which colocalized with putative tyrosine sulfation sites. Calliphora oogenesis differs from Drosophila in that it is cyclic in response to a meat feed. The Calliphora yp genes are expressed in the follicle cells of the egg chamber during vitellogenesis, as shown by in situ hybridization, and the yp message levels correlate with YP synthesis. The synthesis of the yp transcripts in ovaries of Calliphora occurs in the same pattern as that for ovarian transcripts in Drosophila. In the carcass, yp transcript levels are correlated with the production of a batch of eggs. PMID- 8007003 TI - Junctions between repetitive DNAs on the PSR chromosome of Nasonia vitripennis: association of palindromes with recombination. AB - The Paternal-Sex-Ratio (PSR) chromosome of Nasonia vitripennis contains several families of repetitive DNAs that show significant sequence divergence but share two palindromic regions. This study reports on the analysis of junctions between two of these repetitive DNA families (psr2 and psr18). Three lambda clones that hybridized to both repeat families were isolated from PSR-genomic DNA libraries through multiple screenings and analyzed by Southern blots. Analysis of clones showed a region in which the two repeat types are interspersed, flanked by uniform blocks of each repeat type. PCR amplification of genomic DNA confirmed the contiguous arrangement of psr2 and psr18 on PSR and identified an additional junction region between these repeats that was not present in the lambda inserts. We isolated and sequenced 41 clones from the lambda inserts and genomic PCR products containing junction sequences. Sequence analysis showed that all transitions between psr2 and psr18 repeats occurred near one of the two palindromes. Based on the inheritance pattern of PSR, recombination between repeats on this chromosome must be mitotic (rather than meiotic) in origin. The occurrence of exchanges near the palindromes suggests that these sequences enhance recombination between repeat units. Rapid amplification of repetitive DNA may have been an important factor in the evolution of the PSR chromosome. PMID- 8007004 TI - Chimeric evolution of the 2-microns genome in Saccharomyces cerevisiae. AB - We compared the nucleotide substitution pattern over the entire genome of two unique variants of the 6,300-bp selfish DNA (2 microns) plasmid in Saccharomyces cerevisiae. The DNA sequence of the left-unique region is identical among 2 microns variants, while the right-unique region shows substantial divergence. This chimeric pattern cannot be explained by neutral or Darwinian selection models. We propose that horizontal transmission of the 2-microns plasmid coupled with a directed, polarized gene conversion maintains the DNA sequence of the left unique region, whereas the right-unique region is subject to random drift and Darwinian selection. PMID- 8007006 TI - The evolution of proteins from random amino acid sequences: II. Evidence from the statistical distributions of the lengths of modern protein sequences. AB - This paper continues an examination of the hypothesis that modern proteins evolved from random heteropeptide sequences. In support of the hypothesis, White and Jacobs (1993, J Mol Evol 36:79-95) have shown that any sequence chosen randomly from a large collection of nonhomologous proteins has a 90% or better chance of having a lengthwise distribution of amino acids that is indistinguishable from the random expectation regardless of amino acid type. The goal of the present study was to investigate the possibility that the random origin hypothesis could explain the lengths of modern protein sequences without invoking specific mechanisms such as gene duplication or exon splicing. The sets of sequences examined were taken from the 1989 PIR database and consisted of 1,792 "super-family" proteins selected to have little sequence identity, 623 E. coli sequences, and 398 human sequences. The length distributions of the proteins could be described with high significance by either of two closely related probability density functions: The gamma distribution with parameter 2 or the distribution for the sum of two exponential random independent variables. A simple theory for the distributions was developed which assumes that (1) protoprotein sequences had exponentially distributed random independent lengths, (2) the length dependence of protein stability determined which of these protoproteins could fold into compact primitive proteins and thereby attain the potential for biochemical activity, (3) the useful protein sequences were preserved by the primitive genome, and (4) the resulting distribution of sequence lengths is reflected by modern proteins. The theory successfully predicts the two observed distributions which can be distinguished by the functional form of the dependence of protein stability on length. The theory leads to three interesting conclusions. First, it predicts that a tetra-nucleotide was the signal for primitive translation termination. This prediction is entirely consistent with the observations of Brown et al. (1990a,b, Nucleic Acids Res 18:2079-2086 and 18: 6339-6345) which show that tetra-nucleotides (stop codon plus following nucleotide) are the actual signals for termination of translation in both prokaryotes and eukaryotes. Second, the strong dependence of statistical length distributions on sequence-termination signaling codes implies that the evolution of stop codons and translation-termination processes was as important as gene splicing in early evolution. Third, because the theory is based upon a simple no exon stochastic model, it provides a plausible alternative to a limited universe of exons from which all proteins evolved by gene duplication and exon splicing (Dorit et al. 1990, Science 250:1377-1382). PMID- 8007005 TI - Novel features of metazoan mtDNA revealed from sequence analysis of three mitochondrial DNA segments of the land snail Albinaria turrita (Gastropoda: Clausiliidae). AB - The mitochondrial DNA (mtDNA) size of the terrestrial gastropod Albinaria turrita was determined by restriction enzyme mapping and found to be approximately 14.5 kb. Its partial gene content and organization were examined by sequencing three cloned segments representing about one-fourth of the mtDNA molecule. Complete sequences of cytochrome c oxidase subunit II (COII), and ATPase subunit 8 (ATPase8), as well as partial sequences of cytochrome c oxidase subunit I (COI), NADH dehydrogenase subunit 6 (ND6), and the large ribosomal RNA (lrRNA) genes were determined. Nine putative tRNA genes were also identified by their ability to conform to typical mitochondrial tRNA secondary structures. An 82-nt sequence resembles a noncoding region of the bivalve Mytilus edulis, even though it might contain a tenth tRNA gene with an unusual 5-nt overlap with another tRNA gene. The genetic code of Albinaria turrita appears to be the same as that of Drosophila and Mytilus edulis. The structures of COI and COII are conservative, but those of ATPase8 and ND6 are diversified. The sequenced portion of the lrRNA gene (1,079 nt) is characterized by conspicuous deletions in the 5' and 3' ends; this gene represents the smallest coelomate lrRNA gene so far known. Sequence comparisons of the identified genes indicate that there is greater difference between Albinaria and Mytilus than between Albinaria and Drosophila. An evolutionary analysis, based on COII sequences, suggests a possible nonmonophyletic origin of molluskan mtDNA. This is supported also by the absence of the ATPase8 gene in the mtDNA of Mytilus and nematodes, while this gene is present in the mtDNA of Albinaria and Cepaea nemoralis and in all other known coelomate metazoan mtDNAs. PMID- 8007007 TI - The evolution of titin and related giant muscle proteins. AB - Titin and twitchin are giant proteins expressed in muscle. They are mainly composed of domains belonging to the fibronectin class III and immunoglobulin c2 families, repeated many times. In addition, both proteins have a protein kinase domain near the C-terminus. This paper explores the evolution of these and related muscle proteins in an attempt to determine the order of events that gave rise to the different repeat patterns and the order of appearance of the proteins. Despite their great similarity at the level of sequence organization, titin and twitchin diverged from each other at least as early as the divergence between vertebrates and nematodes. Most of the repeating units in titin and twitchin were estimated to derive from three original domains. Chicken smooth muscle myosin light-chain kinase (smMLCK) also has a kinase domain, several immunoglobulin domains, and a fibronectin domain. From a comparison of the kinase domains, titin is predicted to have appeared first during the evolution of the family, followed by twitchin and with the vertebrate MLCKs last to appear. The so called C-protein from chicken is also a member of this family but has no kinase domain. Its origin remains unclear but it most probably pre-dates the titin/twitchin duplication. PMID- 8007009 TI - DNA-dependent RNA polymerase subunit B as a tool for phylogenetic reconstructions: branching topology of the archaeal domain. AB - The branching topology of the archaeal (archaebacterial) domain was inferred from sequence comparisons of the largest subunit (B) of DNA-dependent RNA polymerases (RNAP). Both the nucleic acid sequences of the genes coding for RNAP subunit B and the amino acid sequences of the derived gene products were used for phylogenetic reconstructions. Individual analysis of the three nucleotide positions of codons revealed significant inequalities with respect to guanosine and cytosine (GC) content and evolutionary rates. Only the nucleotides at the second codon positions were found to be unbiased by varied GC contents and sufficiently conserved for reliable phylogenetic reconstructions. A decision matrix was used for the combination of the results of distance matrix, maximum parsimony, and maximum likelihood methods. For this purpose the original results (sums of squares, steps, and logarithms of likelihoods) were transformed into comparable effective values and analyzed with methods known from the theory of statistical decisions. Phylogenetic invariants and statistical analysis with resampling techniques (bootstrap and jackknife) confirmed the preferred branching topology, which is significantly different from the topology known from phylogenetic trees based on 16S rRNA sequences. The preferred topology reconstructed by this analysis shows a common stem for the Methanococcales and Methanobacteriales and a separation of the thermophilic sulfur archaea from the methanogens and halophiles. The latter coincides with a unique phylogenetic location of a characteristic splitting event replacing the largest RNAP subunit of thermophilic sulfur archaea by two fragments in methanogens and halophiles. This topology is in good agreement with physiological and structural differences between the various archaea and demonstrates RNAP to be a suitable phylogenetic marker molecule. PMID- 8007010 TI - Detection of K-ras mutation in colonic effluent samples from patients without evidence of colorectal carcinoma. AB - BACKGROUND: K-ras gene mutation appears in more than 50% of patients with colon tumors. Both its frequency and early appearance may qualify this mutation as a potential biomarker. To enable early detection of mutant K-ras alleles, we had previously developed a sensitive polymerase chain reaction (PCR)-based assay, i.e., enriched PCR, which enables detection of one mutant K-ras allele present within 10,000 normal alleles. Using the enriched PCR, we were able to detect mutant K-ras alleles in "normal-appearing" colonic mucosa in patients with colorectal cancer. PURPOSE: A study was initiated to determine whether mutant K ras alleles could be identified in colonic effluent samples of patients who may be at risk to develop colorectal cancer. METHODS: Over 9 years, colonic effluent samples were collected prior to routine colonoscopy from 39 patients who were apparently free of colorectal cancer. These samples were collected from patients with a family history of colorectal cancer (n = 7), adenomatous polyps (n = 7), previously resected colorectal cancer (n = 5), inflammatory bowel disorders (n = 13), normal colonoscopic examination (n = 6), and familial adenomatous polyposis (n = 1). All of the samples were double coded and analyzed for K-ras gene mutation. RESULTS: Of the 39 patients, seven were found to harbor mutant K-ras codon 12 alleles. Mutations were found in patients with a family history of colorectal cancer (three of seven), adenomatous polyps (one of seven), previously resected colorectal carcinoma (two of five), and familial adenomatous polyposis (one of one). In one case, effluent was found to harbor a mutant K-ras allele 4 years before the patient was diagnosed with colorectal cancer. CONCLUSIONS: (a) Effluent samples contain enough DNA to be detected with enriched PCR. Such samples may well be representative of the entire colon in general as opposed to a localized area such as that usually analyzed during colonoscopy. (b) K-ras gene mutation can be identified in routinely obtained colonic washings of patients who are at risk of developing colorectal cancer. Such mutations were absent in patients with inflammatory bowel disorders and in those who had undergone normal colonoscopic examinations. Detection of K-ras mutation in colonic washings may assist in identifying patients who may be at high risk for developing adenocarcinoma of the colon. IMPLICATIONS: The ability to examine colonic effluents provides a powerful and convenient source of sampling and may be adapted for future large-scale screening. PMID- 8007008 TI - Molecular phylogenies based on ribosomal protein L11, L1, L10, and L12 sequences. AB - Available sequences that correspond to the E. coli ribosomal proteins L11, L1, L10, and L12 from eubacteria, archaebacteria, and eukaryotes have been aligned. The alignments were analyzed qualitatively for shared structural features and for conservation of deletions or insertions. The alignments were further subjected to quantitative phylogenetic analysis, and the amino acid identity between selected pairs of sequences was calculated. In general, eubacteria, archaebacteria, and eukaryotes each form coherent and well-resolved nonoverlapping phylogenetic domains. The degree of diversity of the four proteins between the three groups is not uniform. For L11, the eubacterial and archaebacterial proteins are very similar whereas the eukaryotic L11 is clearly less similar. In contrast, in the case of the L12 proteins and to a lesser extent the L10 proteins, the archaebacterial and eukaryotic proteins are similar whereas the eubacterial proteins are different. The eukaryotic L1 equivalent protein has yet to be identified. If the root of the universal tree is near or within the eubacterial domain, our ribosomal protein-based phylogenies indicate that archaebacteria are monophyletic. The eukaryotic lineage appears to originate either near or within the archaebacterial domain. PMID- 8007011 TI - p53 mutation, expression, and DNA ploidy in evolving gliomas: evidence for two pathways of progression. AB - BACKGROUND: Two lines of evidence indirectly implicate the tumor suppressor p53 (also known as TP53) gene in glioma development. First, germline mutations of the p53 gene are associated with increased susceptibility to glioma. Second, chromosome 17p deletions and p53 gene mutations are found frequently in sporadic gliomas of all malignancy stages. These observations suggest that mutations of the p53 gene may be early events in glioma development. PURPOSE: Our purpose was to analyze 15 low-grade astrocytic gliomas that progressed to higher-grade gliomas, examining the status of the p53 gene in both the initial and recurrent tumors. Also, we explored the relationships between p53 status, DNA ploidy, tumor grade, and patient survival. METHODS: Fifteen low-grade gliomas that recurred as tumors of higher grade 17-102 months after initial treatment (biopsy, resection, radiotherapy, or chemotherapy) were identified from hospital records of patients (eight male and seven female) aged 31-68 years. Pathologic diagnosis was re evaluated. Polymerase chain reaction (PCR)-single-strand conformation polymorphism and DNA sequencing were performed on tissue samples from the initial and recurrent tumors of each patient, using oligonucleotide PCR primers directed to exons 5-9 of the p53 gene. p53 expression was determined by immunohistochemistry and DNA ploidy evaluated by DNA flow cytometry. RESULTS: Eight (53%) of fifteen tumors had p53 mutations in exons 5-9. Nine (64%) of fourteen were immunopositive initially, and eight of these were also immunopositive at recurrence. p53 gene status was significantly associated with p53 expression in the initial tumor (P = .02), and p53 expression at initial diagnosis was significantly related to tumor pathology at recurrence (P = .03). Patients with p53 mutant tumors survived nearly twice as long as those without mutations (median survival, 61 versus 33 months; P = .031). There was no significant difference in recurrence-free survival between patients with p53 mutant and nonmutant tumors (48 versus 33 months; P = .37), but there was a significant difference in postrecurrence survival (17 versus 2 months; P = .019). CONCLUSION: Low-grade tumors that recurred as anaplastic gliomas were characterized by p53 gene mutation, immunopositivity, and DNA non-diploidy. Low grade tumors that recurred as glioblastomas generally had intact p53 genes and were immunonegative. These findings suggest that histologically indistinguishable, low-grade astrocytic gliomas that are destined to progress to higher grades, do so along two distinct clinicopathologic pathways (either stepwise to anaplastic glioma, then glioblastoma, or directly to glioblastoma) marked by the presence or absence of p53 mutation. PMID- 8007012 TI - Re: Endometrial cancer in tamoxifen-treated breast cancer patients: findings from the National Surgical Adjuvant Breast and Bowel Project (NSABP) B-14. PMID- 8007013 TI - Re: Cancer risk after iodine-131 therapy for hyperthyroidism. PMID- 8007015 TI - Molecular screening--how long can we afford to wait? PMID- 8007016 TI - Breast cancer prevention trial will resume. PMID- 8007017 TI - RAC conditionally approves lung cancer gene therapy. PMID- 8007014 TI - An added dimension: will three-dimensional cultures improve our understanding of drug resistance? PMID- 8007018 TI - Clinical results of three-dimensional conformal irradiation. PMID- 8007019 TI - Rapid acquisition of multicellular drug resistance after a single exposure of mammary tumor cells to antitumor alkylating agents. AB - BACKGROUND: Clinical drug resistance is either intrinsic (de novo) or often acquired rapidly in conjunction with chemotherapy. By contrast, the selection of drug-resistant mutant cell lines in monolayer culture systems is usually a more protracted process. Sublines of mouse EMT-6 mammary tumor cells selected for resistance to various alkylating agents in vivo after serial passage into syngeneic mice manifest their resistance in vitro only when cultured as three dimensional multicellular aggregates or spheroids. PURPOSE: We examined whether a single exposure of mouse EMT-6 or human MDA-MB-231 breast cancer cells to alkylating agents in vitro is sufficient for the induction of a resistance phenotype, which may be detected by re-applying the drugs to cells grown as three dimensional aggregates. METHODS: Mouse EMT-6 and human MDA-MB-231 breast cancer cells cultured as three-dimensional aggregates were exposed to a single dose of alkylating agent for 1-5 days. Aggregates were dispersed, and cells were plated as monolayer cultures for up to 8 weeks to allow for recovery. Colony-forming ability was assessed after a subsequent alkylating-agent exposure of cells cultured as monolayers or three-dimensional aggregates. RESULTS: A single in vitro exposure to 12.5-microM cisplatin (CDDP) for 5 days or 25 microM 4 hydroperoxycyclophosphamide (4-O2H CTX) for 1 or 3 days without changing the medium was sufficient to induce transient but substantial resistance in EMT-6 cells as determined by clonogenic assays. Such resistance was not detected when monolayer cell cultures were used. The concentration of 4-O2H-CTX and the length of time the cells remained in three-dimensional culture after initial exposure to this drug was associated with the degree of subsequent drug resistance of cells grown as three-dimensional cultures. Furthermore, this acquired resistance after a single drug exposure was accompanied by changes in the three-dimensional architecture of the cell aggregates, which now formed much more compact multicellular spheroids. Similarly, a single exposure to 4-O2H-CTX was enough to bring about resistance in MDA-MB-231 cells detectable only in three-dimensional cultures, as well as the change in three-dimensional architecture. CONCLUSIONS: Rapid acquisition of resistance likely represents a physiologic mechanism of adaptation operative at the multicellular level rather than a stable genetic change and may be one of the reasons for the rapid development of drug resistance acquired by tumors in vivo. IMPLICATIONS: In vivo drug exposure may result in transient and low levels of drug resistance that may nevertheless be clinically relevant. PMID- 8007020 TI - Lung cancer risk and radiation dose among women treated for breast cancer. AB - BACKGROUND: Evidence shows ionizing radiation can cause lung cancer, but few studies have quantified risk in relation to radiation dose. PURPOSE: This study evaluated the long-term risk of lung cancer among women treated with radiation for breast cancer. METHODS: In this case-referent study, the Connecticut Tumor Registry was used to identify women diagnosed with histologically confirmed invasive breast cancer between 1935 and 1971 who survived for at least 10 years (8976) and to ascertain lung cancers occurring in this group between 1945 and 1981. Seventy-six cases of lung cancer were identified; however, 15 cases did not meet the criteria for inclusion. For the 61 remaining lung cancer case patients and 120 reference subjects (selected from the same registry and matched according to race, age at breast cancer diagnosis, year of breast cancer diagnosis, and survival without a second primary tumor), hospital charts were reviewed to collect medical history and radiotherapy information. A medical physicist estimated radiation dose to different segments of the lungs on the basis of radiotherapy reports and experimental simulations of treatments. RESULTS: For these 10-year survivors of breast cancer, the overall relative risk (RR) of lung cancer associated with initial radiotherapy for breast cancer was 1.8 (95% confidence interval [CI] = 0.8-3.8), and the RR increased with time following treatment. The RR for periods of 15 years or more after radiotherapy was 2.8 (95% CI = 1.0-8.2). Mean dose was 15.2 Gy to the ipsilateral lung, 4.6 Gy to the contralateral lung, and 9.8 Gy for both lungs combined. The excess RR was 0.08 per Gy, based on average dose to both lungs, and 0.20 per Gy to the affected (cancerous) lung. CONCLUSIONS: Breast cancer radiotherapy regimens in use before the 1970s were associated with an elevated lung cancer risk many years following treatment. The estimated risk coefficients are lower than those reported for atomic bomb survivors. The lower than expected risk might be attributable to high dose cell killing or the fractionated nature of the exposure. IMPLICATIONS: Approximately nine cases of radiotherapy-induced lung cancer per year would be expected to occur among 10,000 women who received an average lung dose of 10 Gy and survived for at least 10 years. Current radiotherapy for breast cancer results in less extensive exposure of the lungs in comparison to treatments of years past, and the risk of secondary lung cancer need not play a major role in clinical decisions regarding treatment for breast cancer. Nonetheless, efforts to reduce unnecessary exposure of the lungs and heart should continue to further reduce possible adverse radiation effects. PMID- 8007021 TI - The effect of surface macrotexture on the mechanical and histologic characteristics of hydroxylapatite-coated dental implants. AB - The interface attachment strength and histology of HA-coated endosseous dental implants with surface texturing added to allow for mechanical interlocking of the implant to bone were evaluated in the canine mandibular model. Twenty-two adult mongrel dogs received eight implants (four per side) placed into healed extraction sites. Fifteen weeks post-implantation, the implants were evaluated mechanically by axial pull-out and torsional testing. Following testing, the specimens were evaluated quantitatively for histologic parameters of bone apposition, HA-coating thickness, and mode of interface failure. The addition of surface macrotexture (threads, grooves, and dimples) was not found to have a significant effect on axial pull-out strength compared with smooth implant controls. Similarly, mechanical testing in torsion failed to reveal any significant effect on implant-bone interface attachment due to surface macrotexture. Interface failure occurred primarily at the HA/substrate interface in all implant designs. Examination of HA-coating thickness revealed non-uniform coatings, particularly in the surface-textured designs. Although bone growth into the surface textures was observed in some cases, often only minimal or a thin osseous layer on the HA coating was observed. This factor most likely contributed to the lack of significant additional interface attachment strength in the textured designs. The reduction in areas of complete implant incorporation may also have exposed the HA coating to high interfacial loads and may be responsible for the greater HA coating break-up and presence of particles observed in the textured designs. PMID- 8007022 TI - Tissue response to Bioglass endosseous ridge maintenance implants. AB - Conical devices placed in the alveolar ridge after tooth extraction have been used clinically for several years to maintain the ridge morphology. In this way, the bone atrophy which occurs after extractions is minimized, and denture fit and function are enhanced. A system using such cones made from Bioglass (registered trademark of the University of Florida) and matching burs has been developed and tested clinically. Average four-year data show a retention rate of over 90%, which compares favorably with other systems using other materials (see Hench et al., 1991). Stanley et al. (to be published), in a review of the four-year clinical data, point out that a few of the cones, although firmly positioned within the alveolar ridge, have a radiolucent zone around the implant. In a clinical study, it is not possible to determine whether this radiolucent zone represents areas of fibrous capsule which are not attached to the implant and therefore compromise its long-term stability, or whether the soft tissue is adherent to the implant and thus contributes to its long-term stability. In a recent study, conical implants identical to those in the clinical trial were placed in the alveolar ridges of dogs and evaluated for up to two years. The adhesion of bone and soft tissue was measured and the development and stabilization of the reactive gel layer monitored. The findings in this animal study support the clinical observations and contribute to an explanation of the success of the Bioglass system in patients. PMID- 8007023 TI - Histologic analysis of a screw implant retrieved from man: influence of early loading and primary stability. AB - This paper presents a histologic analysis of a one-piece screw implant put into immediate function and retrieved from man after 7 years of clinical function. Compact lamellar bone with many Haversian canals and osteons was found very near the metal surface, and the morphometric analysis of the perimeter of the implant showed a percentage of bone contact of 86.69% (SD = 5.43). The compact bone was particularly thickened around the top of the spires. At high-power magnification, it was possible to observe optically a small empty gap between bone and titanium, and the use of a histochemical stain (von Kossa) showed that mineralized bone was separated from the metal surface by a very thin layer of unmineralized red stained material; this layer had the same staining features as the osteoid and the osteocyte lamina limitans. PMID- 8007024 TI - An in vivo analysis of an elliptical dental implant design. AB - The interface attachment strength and histology of an elliptical hydroxylapatite coated (HA) endosseous dental implant were compared with those of an otherwise identical cylindrical dental implant. The implant designs were tested in two canine in vivo models: healed mandibular extraction sites and the femoral unicortical plug. The implants were evaluated 15 weeks post-implantation. The elliptical geometry of the dental implant was not found significantly to enhance axial pull-out strength or torsional implant-bone interface attachment in either in vivo model. The cylindrical implant absorbed more energy to failure in both the mandible and the femur; however, the difference was not statistically significant. Differences in the interface shear attachment strength between the two models (mandible and femur) were statistically significant when the maximum load to failure was normalized by the actual bone contact surface area. In all cases, femoral values were significantly greater. Examination of HA-coating thickness revealed uniform coatings on both implant types which were well maintained in vivo. Mechanical failure occurred primarily at the metal substrate HA interface in each type of implant in both models. The amounts of bone apposition to both implants in both models were identical. Coating break-up and inflammatory response to the particulate debris were minimal. PMID- 8007025 TI - An histologic and histomorphometric study of bone reactions to unloaded and loaded non-submerged single implants in monkeys: a pilot study. AB - The authors present an histologic study of bone peri-implant tissue responses to non-submerged unloaded and early-loaded titanium screw implants in monkeys. Titanium screws were placed in the maxillae of 3 Macacus rhesus monkeys. One crown for each of three implants was placed after 30 days under occlusal contact, while the other three implants were left unloaded (one pair per animal). Fifteen months later, the animals were killed, and block sections were obtained to be processed for histology. Thin ground sections were excised so that histomorphometric analyses could be performed. In all samples examined, a tight contact of new bone to the implant surfaces was observed. Moreover, around the implant necks of the early-loaded screws was observed an histologic pattern of lamellar, cortical bone, thicker than in unloaded implants. Comparison with peri implant bone of adjacent teeth showed a similarity to the surfaces of loaded peri implant bone. PMID- 8007026 TI - Management of implant-related problems and infections. AB - Problem-solving and treating various types of infections that can cause alveolar bone loss or inferior alveolar nerve dehiscences by failed implants or teeth are discussed. The reasons why implants fail from either surgical or prosthetic errors are reviewed. Treatment remedies which have solved numerous implant related problems are offered. The eclectic, multi-modal implant surgical and prosthetic abilities of the clinician necessary today for successfully treating patients presenting with troubled or infected implants are reviewed. PMID- 8007027 TI - Clinical case report: an improved technique for using dental implants as orthodontic anchorage. AB - The use of endosseous implants as intra-oral anchorage to facilitate orthodontic treatment has been reported in the literature for some years, first in rabbits and dogs, and then in adult human patients. The implants were generally used solely for the purpose of anchorage. This paper reports the successful application of orthodontic forces utilizing dental implants to achieve tooth movement. The implants were subsequently used as fixtures in a pre-determined plan to support a fixed prosthesis. A clinical example demonstrates how implants may serve dual roles, for anchorage and then for fixed prosthetic support. The principles involved in using dental implants as part of a multi-disciplinary approach to dental treatment are illustrated. PMID- 8007028 TI - Use of subperiosteal implants with a unique composite coating: a case report. AB - The purpose of this study was to evaluate the clinical response to a double composite-coated unilateral subperiosteal implant. The clinical response noted was rapid bony growth over the subperiosteal implant. PMID- 8007030 TI - Laboratory technology. PMID- 8007029 TI - Membrane exposure during bone regeneration before implant placement: management and results. A report of two cases. AB - Two patients with apical lesions on maxillary central incisors showed large osseous defects of the residual ridge. E-PTFE membranes were used for ridge reconstruction, which allowed for the placement of implants of appropriate diameters. In the two cases described, the membranes were exposed and replaced. This technique facilitated atrophic ridge reconstruction in spite of premature membrane exposure. PMID- 8007031 TI - Nebulized sodium bicarbonate in the treatment of chlorine gas inhalation. AB - In this two year retrospective review, 86 cases of chlorine gas inhalation from 49 medical facilities were treated with nebulized sodium bicarbonate on the recommendation of the Kentucky Regional Poison Center. Typical manifestations included cough, chest discomfort, shortness of breath, and wheezing. No patients developed pulmonary edema or respiratory insufficiency requiring ventilatory support. Sixty-three cases (73.3%) were exposures to chlorine producing acid/hypochlorite mixtures. Six (7.0%) were exposed to chlorine gas in industrial settings. Twelve (14.0%) were exposed to chlorine gas in swimming pool settings. Sixty-nine (80.2%) were treated and released from the emergency department. In 53 patients, clinical condition was clearly improved on emergency department discharge. Seventeen (19.8%) were admitted to the hospital. All admitted patients gradually improved and had a mean hospital stay of 1.4 days (range 1 to 3 days). No patients in this study deteriorated clinically after nebulized sodium bicarbonate use. Nebulized sodium bicarbonate appears safe and merits prospective evaluation in the therapy of chlorine gas inhalation. PMID- 8007032 TI - Nitroglycerin in the treatment of cocaine associated chest pain--clinical safety and efficacy. AB - The optimal medical regimen for the treatment of cocaine associated myocardial ischemia has not been defined. While animal and human data demonstrate the risks of beta-adrenergic blockade, studies in the cardiac catheterization laboratory suggest a beneficial role of nitroglycerin. We performed a prospective multicenter observational study to evaluate the clinical safety and efficacy of nitroglycerin in the treatment of cocaine associated chest pain at six municipal hospital centers. Of 246 patients presenting with cocaine associated chest pain, 83 patients were treated with nitroglycerin at the discretion of the treating physician. Relief of chest pain and/or adverse hemodynamic outcome were the primary endpoints. Baseline comparisons of patients treated with nitroglycerin to those not treated with nitroglycerin found that the treated patients were at higher risk of ischemic heart disease. They were older (36 years vs 32 years, p = 0.0008), more likely to have an ischemic electrocardiogram (27% vs 4%, p < 0.0001), to be admitted (94% vs 40%, p < 0.0001), and to have a discharge diagnosis of ischemic heart disease (41% vs 9%, p < 0.0001). Nitroglycerin was beneficial in 41 patients (49%; 95% CI, 38-60%): 37 patients (45%) had relief or reduction in the severity of chest pain and 4 patients (5%) had other beneficial effects. Only one patient had an adverse outcome (transient hypotension in the setting of a right ventricular infarct). Nitroglycerin is safe and possibly effective in the treatment of cocaine associated chest pain. PMID- 8007034 TI - Disappearance of heme metabolites following chelation therapy with meso 2,3 dimercaptosuccinic acid (DMSA). AB - A lead poisoned adult (blood lead level 384 micrograms/dL) had a specific urinary porphyrin profile of elevated porphyrins including coproporphyrin III and 5 carboxylic acid derivatives. A multilinear gradient elution, modified with an ion pair and a reversed phase column were employed for the separation of the diagnostically important porphyrin isomers. Fluorescence detection enhanced both sensitivity and selectivity. Both compounds were restored to normal levels following two courses of meso 2,3-dimercaptosuccinic acid: 90 mg/kg/d x 5 d at one month intervals. The decrease of clinical symptoms was associated with increase of delta aminolevulinic acid dehydratase from 53 to 230 U/mL blood and hemoglobin from 8.4 to 12.7 g/dL. Blood lead decreased from 384 to 24 micrograms/dL, urine lead from 1286 to 188 micrograms/L and urine coproporphyrin III from 5712 to 25 micrograms/L. PMID- 8007033 TI - Adenosine receptors are not involved in theophylline-induced seizures. AB - One of the most dangerous aspects of theophylline toxicity is seizures. A review of the literature suggests that current anticonvulsant therapy remains far from optimal. As it is known that some of the pharmacologic effects of theophylline occur via antagonism of the adenosine A1 receptor, we tested the hypothesis that agonists acting at the adenosine A1 receptor can inhibit seizures caused by toxic doses of theophylline in mice. Dose-response curves were constructed for the ability of theophylline to produce tonic seizures in animals pre-treated with vehicle or several adenosine A1 receptor agonists. The LD50 (95% CI) for each dose-response curve was calculated. The results of these experiments showed that pretreatment with the direct-acting adenosine A1 agonists carbamazepine and cyclohexyladenosine and the indirect-acting agonist dipyridamole each failed to inhibit the ability of theophylline to cause tonic seizures (p > 0.05). Failure of these drugs to protect against theophylline-induced seizures suggests these seizures are produced by other mechanisms. Based on our results, adenosine A1 agonists, such as carbamazepine, appear to offer no therapeutic benefit in the treatment of theophylline-induced seizures. PMID- 8007035 TI - Milrinone versus glucagon: comparative hemodynamic effects in canine propranolol poisoning. AB - Glucagon has been reported to be one of the most effective treatments for severe beta-blocker poisoning. Recently, amrinone was suggested as an alternative therapeutic choice for beta-blocker poisoning. Milrinone, a derivative of amrinone, acts independently of beta-adrenoceptors and increases cyclic AMP. Therefore milrinone may also be effective in the treatment of beta-blocker poisoning. In the present study, we compared the effect of glucagon and milrinone in treating severe beta-blocker poisoning. Following the administration of 10 mg/kg propranolol i.v. over 10 min, heart rate, cardiac output, mean arterial pressure, stroke volume, and end tidal CO2 were depressed, while central venous pressure, and pulmonary capillary wedge pressure increased significantly (p < 0.05). Following the administration of saline (Group S, N = 3), glucagon 20 micrograms/kg (Group G, N = 5), and milrinone 300 micrograms/kg (Group M, N = 5), hemodynamic parameters were observed for 30 min. In group M, mean arterial pressure, cardiac output and stroke volume recovered to their baseline values, while central venous pressure and pulmonary capillary wedge pressure decreased. Although there were no significant differences between groups G and M, the heart rate, central venous pressure and pulmonary capillary wedge pressure, mean arterial pressure and stroke volume did not return to baseline values in group G. Milrinone administration produced a significant hemodynamic improvement without increasing the heart rate in the canine model of severe heart failure caused by propranolol. In the glucagon treatment group, central venous pressure and pulmonary capillary wedge pressure improved less than the milrinone group. Although more data are needed before a clinical recommendation, milrinone might be an effective drug to treat beta-blocker poisoning. PMID- 8007036 TI - Supraventricular tachyarrhythmia associated with baclofen overdose. AB - Baclofen overdose occasionally results in cardiac effects, but serious tachyarrhythmias have not been reported. We present the case of a 21-year-old man with an acute baclofen overdose who developed increased cardiac conduction times and a rapid supraventricular tachyarrhythmia which required medical intervention. Acute baclofen toxicity can result in the development of tachyarrhythmias and cardiac monitoring is warranted in acute overdose states. PMID- 8007037 TI - Methemoglobinemia: an occupational hazard of phenylpropanolamine production. AB - Two workers from the same factory presented to the same emergency department within six weeks of one another with moderate (Case 1) and severe (Case 2) methemoglobinemia. Subsequent investigation revealed that the factory produces phenylpropanolamine and that both patients, shortly before becoming ill, were inadvertently exposed to methyl nitrite, a critical reagent in this production. Although other nitrites induce methemoglobinemia, exposure to methyl nitrite during phenylpropanolamine production appears to be a new cause of occupational methemoglobinemia. PMID- 8007038 TI - Ketorolac induced acute renal failure following a single dose. AB - Acute and chronic impairment of renal function have been reported as complications of therapy with nonsteroidal anti-inflammatory agents. Renal prostaglandins play an increasingly important role in maintaining renal function when there is decreased renal blood perfusion. We describe a case of rapidly appearing acute renal failure following a single intramuscular dose of ketorolac. PMID- 8007039 TI - Ketorolac. PMID- 8007040 TI - Ibuprofen overdose complicated by renal failure, adult respiratory distress syndrome, and metabolic acidosis. AB - Acute ingestion of ibuprofen commonly results in no symptoms, or minor gastrointestinal or central nervous system manifestations. While most cases of ibuprofen overdose do well, serious toxicity may occur, and is difficult to predict. A case of ibuprofen overdose is presented in which the course was complicated by metabolic acidosis, adult respiratory distress syndrome, and renal failure necessitating prolonged dialysis. PMID- 8007041 TI - Nitroethane poisoning from an artificial fingernail remover. AB - Confusion between acetone fingernail polish removers and artificial fingernail products containing acetonitrile and N,N-dimethyl-p-toluidine has resulted in pediatric morbidity and mortality. In the present case, a 20-month-old boy drank less than one ounce of Remove Artificial Nail Remover containing 100% nitroethane. In the emergency department he displayed cyanosis and 39% methemoglobinemia. Following intravenous methylene blue, the child's methemoglobin level dropped to 5.7% and he recovered uneventfully. Toxicity from nitroethane has not previously been reported in humans. Poison centers and emergency department personnel should be alert to another nail product which may be easily confused with acetone-containing nail polish removers. PMID- 8007042 TI - Meperidine neurotoxicity after organ transplantation. AB - Meperidine neurotoxicity, characterized by recurrent convulsions, myoclonus, and asterixis, was diagnosed in an organ transplant recipient. Aside from cyclosporine toxicity, the literature regarding neurologic complications of transplantation contains limited reference to the neurotoxicity of therapy. The case reported illustrates how pharmacokinetic factors might render transplant patients particularly vulnerable to the neurotoxic side effects of certain medications, such as meperidine. PMID- 8007043 TI - Poisoning by the use of Datura leaves in a homemade toothpaste. AB - Datura stramonium and related species are relatively common causes of atropine like poisoning by ingestion or inhalation. Toxic absorption after mucosal application is evident in 24 h of atropinism sustained by a woman who used a toothpaste mixed with the leaves and flowers of Datura sp., table salt, vinegar and an alcoholic beverage. PMID- 8007044 TI - Acetic acid intoxication by rectal administration. AB - The enhanced toxicity of acid instilled directly into the rectum, without benefit of dilution and neutralization in the upper intestine, is evident in a case of acetic acid intoxication by accidental rectal administration of 50 mL of 9% acetic acid to a 5-year-old boy. The complications included necrosis of the colon, acute renal failure, acute liver dysfunction, disseminated intravascular coagulopathy (DIC) and sepsis. PMID- 8007045 TI - Establishment and characterization of a continuous human basal cell carcinoma cell line from facial skin (I) cytological behavior of early passages. AB - Basal cell carcinomas (BCCs) are one of the most common skin malignant diseases of human beings in the course of a lifetime. BCC is a slow growing tumor of epithelial origin. Most of the BCC tumors have a normal diploid DNA configuration and have been successfully passaged for a short-term only. We now report a long term culture (BCC-1/KMC) of human BCC derived from the undifferentiated type of facial BCC tumor on the thermal traumatic scar, which was aneuploidy and subculture for more than 100 passages. The population doubling time of BCC-1/KMC cells at the third passage was 38.86 hours. This immortalized and tumorigenic cell line expresses epithelial markers of keratin filaments and desmosomes. The genetic markers of this cell line have HLA-A2, A24, B27, B35, Cw3, DR2 and DR12. The BCC-1/KMC cells have successfully adapted to grow in a cheaper commercial medium (RPMI 1640) and at a moderate concentration of calcium (0.4 mM). PMID- 8007046 TI - Management of the perineal wounds following excision of the rectum for malignancy. AB - In a retrospective study, 103 patients undergoing abdominoperineal resection or total proctocolectomy due to rectal adenocarcinoma or familial polyposis with malignant change in the rectum were included. The methods for treating the pelvic and perineal wounds were divided into four categories: (1) suture of the pelvic peritoneum with open drainage, (2) suture of the pelvic peritoneum and perineum with simple drainage, (3) suture of the pelvic peritoneum and perineum with suction drainage, and (4) suture of the perineum with omental pedicle graft. The parameters analyzed were incidence of perineal wound infection, primary healing of the perineum, extraperineal complications and mean hospital stay. The infective rate of the group 1 was significantly higher than for the other groups. The incidence of primary wound healing for groups 2, 3, 4 was 73%, 78%, 81% respectively compared with group 1 of 20% at one month. There was no significant difference between the various groups regarding extraperineal complications. There was no significant difference in hospital stay among groups 2, 3, 4, but they were significantly shorter than for group 1. Primary closure of the pelvic peritoneum and perineal wound with simple drainage is now adopted by us due to its low infection rate, short hospital stay and easy performance. PMID- 8007047 TI - Nucleolar organizer regions in small cell carcinoma of lung. AB - Agyrophilic staining of nucleolar organizer regions (NOR) has been used to differentiate between cells of small cell carcinoma and lymphocytes in tissue specimens. We used cytologic smears which were previously Papanicolaou-destained to study the one-step agyrophilic staining technique for nucleolar organizer regions (AgNOR) in cell of small cell carcinoma and lymphocyte. The purposes of this study were to assess the feasibility and usefulness of AgNOR staining in diagnostic cytology and to try to set up a procedure that could be used on prestained smears for retrospective study. While the NOR of each lymphocyte appeared to be one round dot after AgNOR staining, the NOR of cell of small cell carcinoma showed dots, slightly variable in size and shape. The mean number of NOR was significantly higher (p < 0.01) in cells of small cell carcinoma (4.7 +/- 0.7) than in lymphocytes (1.4 +/- 0.4). In conclusion, AgNOR staining was demonstrated to be a useful method to differentiate between cells of small cell carcinoma and lymphocyte in Papanicolaou-destained smears. PMID- 8007048 TI - MRI manifestations of leptomeningeal metastasis. AB - Twenty-six cases with leptomeningeal metastasis were analyzed and Gd-DTPA enhanced MR imaging was found to be the most useful tool for making the diagnosis. The important manifestations in order of frequency were: 1) leptomeningeal enhancement; 2) ependymal enhancement; 3) plaque, nodule or mass in the subarachnoid space or ventricles; 4) nerve root thickening; and 5) ventricular dilatation not related to the obstruction of the primary neoplasm. A review of the literature has shown that intracranial leptomeningeal metastasis from spinal cord astrocytoma are very rare. In our series, 3 cases with primary brain tumors developed spinal subarachnoid involvement. This paper also reviews 1 case with thoracic cord astrocytoma which developed multiple intracranial leptomeningeal metastasis. PMID- 8007049 TI - Magnetic resonance imaging and computed tomography of transitional cell carcinoma of renal pelvis and ureter. AB - Fourteen patients with clinically suspicious transitional cell carcinoma of renal pelvis or ureter were preoperatively examined with magnetic resonance imaging (MRI) and computed tomography (CT). All of the cases had surgical approval. In eleven of these patients, the tumor was correctly detected by MRI. Two cases were falsely positive including one squamous cell carcinoma (SCC) and one Wilms' tumor of the kidney. The final case was falsely negative. The positive predictive value of MRI was 92.9%. The sensitivity was 91.7%. In seven of the fourteen patients, the CT findings were truly positive. There were five falsely negative findings and two falsely positive cases. The positive predictive value by CT was 64.3%. The sensitivity was 59.3%. Tumor stagings were done for all patients. The accuracy rate of staging was 7/7 by CT and 10/11 by MRI. MRI showed better identification of distant metastasis in the liver, vertebrae and vascular structure because of its high tissue contrast and larger field of view. MRI had a higher positive predictive rate and sensitivity for identification of uroepithelial tumor than CT. PMID- 8007050 TI - MR imaging of sports-related muscle injuries. AB - Magnetic resonance (MR) imaging of the thighs of 26 baseball athletes and one softball athlete were studied to evaluate muscle injuries. We documented the abnormalities present in MR imaging after a muscle injury and evaluated the role of MR imaging in muscle injuries. Fifteen of the athletes showed muscle abnormalities in MR images. These include muscle strains without tear, muscle tear, scar and chronic tendon injury. Having the advantages of high tissue contrast and multiplanar display capability, MR allowed direct visualization of the injured muscles and characterization of traumatic lesions. We conclude that MR could be a good imaging modality for evaluating muscle injuries. PMID- 8007051 TI - [Study on cutaneous physio-immuno-pathological status in tinea versicolor]. AB - This study examined 20 cases of tinea versicolor to assess the dermato physiological, immunological and pathological status of lesion sites as compared to 20 normal control subjects. Lesion sites showed a significant decrease in sebaceous gland secretions and water content and an increase in pH value compared to normal skin. There was no significant change in involucrin, filaggrin, or number of stratum corneum cell layers. However, lesions showed weak positive staining of IL-1 alpha. A possible mechanism for these changes is that profuse sweat gland secretions predispose to fungal growth and acid mantle destruction, with the pathogens consuming amino acids and sebum as nutrients. Slight increases in IL-1 alpha levels seen in infected areas could be due to a fungus-stimulated immune reaction in the stratum corneum. PMID- 8007052 TI - Delayed intracerebral tension pneumocephalus--report of two cases. AB - Two patients were found with delayed intracerebral tension pneumocephalus 5 and 12 months later, following head injury. Simple skull X-ray showed a large air containing cyst in the left frontal lobe in both cases. Dural repairs were done through an intradural approach via single frontal craniotomy. Basal skull fracture with dural tear at cribriform plate of ethmoid bone and intracerebral cyst filled with air were found during operation. Their deteriorated consciousness became clear post-operatively. Plain computed tomography was a very useful instrument in determining the location of the gas collection, fracture site, and tension on the brain. PMID- 8007053 TI - Major and minor surgery at a rural African hospital. AB - Surgical operations performed at Ombo Hospital in Western Kenya from January to December 1989 were studied and annual surgical rates were calculated based on the estimated catchment area population. The total annual rate of major surgery at this church-supported hospital was 207 operations per 100,000 people. This rate is similar to those at other East African hospitals while rates in industrialized countries are 20-35 times higher. The most common major procedures were Caesarean section, laparotomy, hernia repair and salpingectomy. The 1989 rate of minor operations at the hospital was 1286 per 100,000 people with tooth extraction, wound suture, incision and drainage, evacuation of the uterine cavity and closed reduction of fracture as the most frequent procedures. Major operations were performed exclusively by doctors while minor surgery was carried out mainly by clinical officers, nurses and other auxiliary staff. PMID- 8007054 TI - A prospective investigation of the long-term auditory-neurological sequelae associated with bacterial meningitis: a study from Vanuatu. AB - During the period August 1988-July 1991 all cases of bacterial meningitis admitted to Lenakel Hospital on the island of Tanna in Vanuatu were followed. During this period there were 83 cases of purulent meningitis giving an annual incidence of 134 per 100,000 population. There were 13 deaths during the acute illness phase (CFR = 15.7%). Of the 70 survivors 65 (93%) were successfully followed for a mean duration of 17.5 months. When grouped by severity of illness there was no significant difference in the mean age, duration of symptoms or sex of the patients. At the time of discharge 31.5% had auditory-neurological abnormalities. During follow-up 35% of the survivors were found to have one or more auditory-neurological sequelae. Hearing loss was the most frequent abnormality occurring in 32.2% of the study group. Of those with auditory neurological sequelae 39% were judged to have severe disabilities likely to impair their ability to live independently. A statistically significant association was found between the severity of the illness at presentation and the risk of auditory-neurological sequelae. Meningitis caused by Streptococcus pneumoniae was associated with the highest incidence of sequelae and that caused by Hemophilus influenzae type b with the lowest. There was no association with sex or age group. Strategies to reduce the mortality and morbidity from bacterial meningitis in developing countries are briefly discussed. PMID- 8007055 TI - Stand-by treatment of malaria in travellers: a review. AB - Stand-by treatment is the use of anti-malaria drugs carried for self administration when fever and flu-like symptoms occur and prompt medical attention is not available. This paper aims to review the rationale for the stand by therapy concept, the range of options available, the factors influencing the choice of therapy and the efficacy and toxicity of the various agents available in the light of ever increasing resistance to conventional drugs. The use of chloroquine as a possible stand-by treatment is limited because of widespread chloroquine resistance and the problem is further compounded by the increasing prevalence of parasites resistant to antifolate/sulpha drug combinations, particularly in South-East Asia and South America. Mefloquine is a promising agent for presumptive malarial treatment with limited foci of drug resistance, notably in Thailand. Mefloquine therapy has been associated with adverse events, mostly minor but with occasional neuropsychiatric events. The use of halofantrine, hitherto often recommended as a stand-by treatment, has been curtailed after recent research reports demonstrated that the drug may cause prolongation of the QTc interval. Current experience with stand-by therapy is limited and studies are in progress to elucidate the exact circumstances under which travellers actually use their emergency medication. Stand-by treatment is an option for clearly defined situations while prophylaxis remains the safest choice for travellers to areas of high transmission. PMID- 8007056 TI - Transferable drug resistance (R-factor) among the enterobacteriaceae in urinary tract infections: a study at an urban hospital in Bangladesh. AB - Prevalence and patterns of drug resistance were studied among Enterobacteriaceae, isolated from the cases of urinary tract infection (UTI) attending at an outpatient department of an urban hospital in Dhaka. Out of 90 Enterobacteriaceae isolated, 95.5% were resistant to the different antimicrobials tested. The most common resistance pattern observed was against ampicillin (A), trimethoprim (Tm), sulphamethoxazole (S), tetracycline (T) and chloramphenicol (C) in all four genera of Enterobacteriaceae. Transferable drug resistance (R(+)-factor) was detected in 68.5% Escherichia coli (E. coli), 60% Klebsiella, 66.6% Proteus and 50% Citrobacter strains. By using a resistance transfer factor (RTF) mobilizing strain, resistance factors were transferred from 3 (11.3%) out of 26 non autotransferable strains. The study revealed that transferable drug resistance is common in organisms isolated from UTI in Bangladesh. PMID- 8007057 TI - Distribution patterns of Tunga penetrans within a community in Trinidad, West Indies. AB - This paper describes patterns of infection with Tunga penetrans within the town of Icacos, Trinidad, West Indies, assessed by the number of persons infected and the extent of the chigoe flea burden by physical examination. The overall prevalence of infection was 31.4% (102 infected persons) of the 325 persons examined (41% of males and 23% of females). Both measures showed a significant difference among the different age groups with peak chigoe burden found in the 5 9, 10-14 and > 55 age-groups, with 9, 5.6 and 12 fleas per infected person, respectively. The aggregated distribution of chigoe flea burden showed a few persons with many fleas and many persons with none (68%). In contrast, in chigoe flea burden there were no significant sex differences but age-associated differences (G = 17.9; d.f. 7; P < 0.01). It is recommended that all cases of tungiasis should be treated and the source of infection effectively managed or eradicated. PMID- 8007059 TI - Severe hypercalcaemia associated with miliary tuberculosis. AB - Hypercalcaemia is uncommon among patients with pulmonary tuberculosis in Hong Kong, possibly because of the low dietary calcium intake in this population. We report here a case of severe hypercalcaemia in a patient with miliary tuberculosis and impaired renal function. We suggest that tuberculosis should be excluded in any febrile patient with hypercalcaemia, particularly in countries where it is still a common condition and an important cause of hypercalcaemia. PMID- 8007060 TI - High prevalence of clinical obesity among Saudi females: a prospective, cross sectional study in the Riyadh region. AB - A cross-sectional study of 1385 Saudi females attending 15 health centres in urban and rural areas in the Riyadh region was conducted during September and October 1992 to determine the prevalence of obesity and its associated factors. The mean age was 32.2 +/- 11.7 years and body mass index (BMI) 29.2 +/- 7.0 kg m 2. Only 26.1% of subjects were their ideal weight (BMI < 25 kg m-2), while 26.8% were overweight (BMI 25-29.9 kg m-2), 41.9% were moderately obese (BMI 30-40 kg m 2) and 5.1% were morbidly obese (BMI > 40 kg m-2). High-risk groups for obesity were mostly middle aged, multiparous housewives. Patients living in rural areas had greater BMIs than those living in urban areas (P < 0.01). Thirty per cent of overweight participants did not think they were overweight. The study emphasizes the need for community based programmes for preventing and reducing obesity since weight control is effective in ameliorating most of the disorders associated with obesity such as Type 2 non-insulin dependent diabetes mellitus, hypertension, stroke, heart disease, sleep apnoea syndrome and osteoarthritis of the knees. The focus of efforts should be directed towards young mothers who are at risk of developing obesity and who play a central role in perpetuating it in their offspring. PMID- 8007058 TI - Usefulness of serum ferritin levels in the assessment of iron status in non pregnant Zairean women of childbearing age. AB - We studied the usefulness of serum ferritin for the assessment of iron deficiency (ID) or ID anaemia (IDA) of 186 lactating and 27 non-lactating Zairean women (15 45 years old). Haemoglobin (Hb), serum iron (SI), total iron binding capacity (TIBC), and transferrin saturation (TS) were also measured. Participants were recruited in rural Bas-Zaire State in the summers of 1986 and 1989. Serum ferritin ranged from 10 to 360 micrograms l-1 (median 62 micrograms l-1) in lactating women and from 14.2 to 120 micrograms l-1 (median 40 micrograms l-1) in non-lactating women. While mean levels of serum ferritin and TS were within the normal range in both groups of women, those of Hb were below normal (< 12 g dl 1), partly due to inflammation. The prevalence of anaemia was 66% in lactating women and 70% in non-lactating women, and did not change with time. It was higher in women with inflammation than in those without inflammation. Although ID (ferritin < 12 micrograms l-1) was almost absent, after raising the cut-off point of ferritin to 50 micrograms l-1 in women with inflammation, it was present in 28.8% of lactating women and 52% of non-lactating women. While the prevalence of ID assessed by serum ferritin was significantly higher in lactating women studied in 1989 (40.5%) than in those studied in 1986 (13.5%), it was similar in both groups of non-lactating women. ID defined by TS < 16% was present in 41% of lactating women and 21% of non-lactating women. In the presence as well as absence of inflammation, the use of TS identified a higher percentage of lactating women with either ID or IDA than did the use of serum ferritin. We conclude that, in the studied population, unless inflammation is taken into consideration, serum ferritin has a limited value in the diagnosis of ID. PMID- 8007061 TI - Corynebacterium diphtheriae endocarditis in an adult with congenital heart disease: a case report. AB - A rare case of septicaemia and endocarditis due to Corynebacterium diphtheriae is presented. The patient had underlying congenital heart disease and died despite high-dose penicillin therapy. The implications for diagnosis and identification and some public health issues brought to the fore by the case are discussed. PMID- 8007062 TI - From the Congressional Office of Technology Assessment. PMID- 8007063 TI - From the Centers for Disease Control and Prevention. Cigarette smoking among adults--United States, 1992, and changes in definition of smoking. PMID- 8007064 TI - From the Centers for Disease Control and Prevention. Invasive group A streptococcal infections--United Kingdom, 1994. PMID- 8007065 TI - From the Centers for Disease Control and Prevention. Birth outcomes following zidovudine therapy in pregnant women. PMID- 8007066 TI - Fetal loss and caffeine intake. PMID- 8007067 TI - Fetal loss and caffeine intake. PMID- 8007068 TI - Fetal loss and caffeine intake. PMID- 8007069 TI - Cardiac function in fetuses with congenital diaphragmatic hernia. PMID- 8007070 TI - Legislating drug prescribing practices. PMID- 8007071 TI - Legislating drug prescribing practices. PMID- 8007072 TI - CEA to detect recurrence of colon cancer. PMID- 8007073 TI - Liability immunity for physician volunteers. PMID- 8007074 TI - Cancer: beliefs and attitudes of migrant Latinos. PMID- 8007075 TI - Nicotine patch for smoking cessation. PMID- 8007076 TI - Left ventricular mass and risk of stroke in an elderly cohort. The Framingham Heart Study. AB - OBJECTIVE: To evaluate the association of echocardiographically determined left ventricular mass (LVM) with incidence of stroke or transient ischemic attack in an elderly cohort. DESIGN: Cohort study with a follow-up period of 8 years. SETTING: Population-based sample. SUBJECTS: Elderly original cohort subjects of the Framingham Heart Study who were free of cerebrovascular disease and atrial fibrillation at the 16th biennial examination and who had adequate echocardiograms. This group consisted of 447 men (mean age, 67.8 years; range, 60 to 90 years) and 783 women (mean age, 69.2 years; range 59 to 90 years). MAIN OUTCOME MEASURES: Age-adjusted 8-year incidence of stroke was examined as a function of baseline quartiles of LVM-to-height ratio. Proportional hazards regression was used in multivariate analyses to assess risk of stroke as a function of LVM-to-height ratio quartile, adjusting for age, sex, systolic blood pressure, hypertension treatment, diabetes, cigarette smoking, and blood lipid levels. RESULTS: Among the 1230 subjects eligible, 89 cerebrovascular disease events (62 strokes and 27 transient ischemic attacks) occurred during follow-up. In men, 8-year age-adjusted incidence of cerebrovascular events was 18.4% in the highest quartile of LVM-to-height ratio and 5.2% in the lowest quartile. Corresponding values in women were 12.2% and 2.9%. The hazard ratio for cerebrovascular events comparing highest to lowest quartile of LVM-to-height ratio was 2.72 (95% confidence interval [CI], 1.39 to 5.36) after adjusting for age, sex, systolic blood pressure, hypertension treatment, diabetes, cigarette smoking, and the ratio of total cholesterol to high-density lipoprotein cholesterol. After adjusting for age, sex, and cardiovascular disease risk factors, the hazard ratio for cerebrovascular events was 1.45 (95% CI, 1.17 to 1.80) for each quartile increment of LVM-to-height ratio. CONCLUSIONS: Echocardiographically determined LVM-to-height ratio offers prognostic information beyond that provided by traditional cerebrovascular disease risk factors. Echocardiography provides information that facilitates identification of individuals at high risk for stroke and transient ischemic attack. PMID- 8007077 TI - How will graduate medical education reform affect specialties and geographic areas? AB - OBJECTIVES: To project specialty and geographic impacts of workforce reform proposals on the practice output of graduate medical education (GME). DESIGN: A demographic life-table model to predict GME output was developed using 1987 cohort data from the Association of American Medical Colleges Annual GME Census. The 1992 GME cohort was used as a baseline to compare the simulated impact of alternate specialty and regional policies. SETTING: Allopathic and osteopathic GME programs in the United States. MAIN OUTCOME MEASURE: Projected number of physicians (MDs and DOs) entering nine categories of practice specialty at the conclusion of GME. RESULTS: If GME input is reduced to 110% of US medical graduates with 55% entering practice as generalists (including obstetrics and gynecology), then the total number of first-year positions will decline from 24,433 to 18,783, and the total number of residents in GME would decline from 103,858 to 80,699 at equilibrium. Even with a 110% restriction on GME input, the overall physician-to-population ratio will continue to grow, albeit at a much slower rate. The number of generalists leaving GME annually would increase by 742 (9%) and the number of specialists would decline by 6517 (44%). At the regional level, allocating GME positions by prorating to the current distribution results in less change than would prorating positions to regional populations. CONCLUSIONS: Achieving national goals of reduced aggregate physician production, reduced specialist supply, and generalist increases will require significant alterations in the GME pool. Adequate time and funding for resident substitution will be required for hospitals to develop alternate models of providing service to allow national workforce goals to be met. PMID- 8007079 TI - Effect of hypnotic suggestion on the delayed-type hypersensitivity response. AB - OBJECTIVE: To determine whether individuals selected for good general health, high hypnotizability, and the ability to alter skin temperature under hypnotic suggestion can influence the delayed-type hypersensitivity (DTH) response to varicella-zoster (VZ) antigen under hypnotic suggestion. DESIGN: A blinded clinical trial using a repeated measures design with subjects serving as their own controls. Subjects were randomly assigned to undergo a predetermined sequence of four different experimental conditions, occurring at weekly intervals, with each condition including VZ skin testing: (1) hypnosis with suggestions to enhance the DTH response to VZ antigen; (2) hypnosis with suggestions to suppress the DTH response; (3) hypnosis with suggestions for relaxation only; and (4) skin testing without hypnosis. SETTING: A National Institutes of Health-supported clinical research center in a teaching hospital. SUBJECTS: A stratified sample of 24 ambulatory, healthy, highly hypnotizable, volunteer college students selected for their above-average ability to alter skin temperature after hypnotic suggestions and their positive baseline responses to VZ antigen. There were 11 males and 13 females with a mean +/- SD age of 22 +/- 6 years. The mean +/- SD hypnotizability score (Harvard Group Scale of Hypnotic Susceptibility) was 11 +/- 1. INTERVENTIONS: Intradermal skin testing with VZ antigen (Mantoux method) and hypnotic suggestion. MAIN OUTCOME MEASURES: Areas of induration of the DTH response measured at 24 and 48 hours after injection of antigen. RESULTS: The area of the DTH response was not affected by the experimental interventions. The area of erythema was likewise unaffected. CONCLUSIONS: Our subjects were unable to alter their DTH responses using hypnotic suggestion. PMID- 8007078 TI - Homicide in New York City. Cocaine use and firearms. AB - OBJECTIVE: To determine differences between racial/ethnic groups in overall rates of death by homicide, proportion of firearm homicides, and the use of cocaine prior to death. DESIGN: Descriptive epidemiologic survey of a complete 2-year sample of homicides. SETTING: New York City, NY (population 7,322,564). SUBJECTS: All residents (N = 4298) of New York City who were victims of homicide during 1990 and 1991. MAIN OUTCOME MEASURES: Using medical examiner data, age- and gender-specific rates of homicide were calculated for African Americans, Latinos, and whites. Separate logistic regression analyses were conducted to examine the association between demographic variables and both recent cocaine use and firearm related homicides. RESULTS: Young African-American and Latino men were more likely to be victims of homicide than all other demographic groups. Approximately three fourths of all homicides involved firearms. In the subset of homicide victims dying within 48 hours (n = 3890), 31.0% were positive for cocaine metabolites. African Americans (odds ratio [OR], 1.6; 95% confidence interval [CI], 1.2 to 2.1), Latinos (OR, 1.4; 95% CI, 1.1 to 1.9), and victims 25 through 34 years of age (OR, 2.9; 95% CI, 2.5 to 3.5) and 35 through 44 years of age (OR, 2.7; 95% CI, 2.2 to 3.4) were more likely to be positive for cocaine metabolites than other groups. Young males and females were equally likely to have used cocaine before death. Victims 15 through 24 years of age were more likely than other age groups to be killed by a firearm. African Americans (OR, 1.7; 95% CI, 1.3 to 2.3), Latinos (OR, 1.5; 95% CI, 1.2 to 2.0), and Asians (OR, 2.2; 95% CI, 1.4 to 3.6) were more likely than whites to be killed by a firearm. Men (OR, 4.8; 95% CI, 4.0 to 5.9) were more likely than women to be killed by a firearm. There was no association between having used cocaine before death and being killed by a firearm. CONCLUSIONS: The high rates of death by homicide among young African Americans and Latinos may be due to the increased involvement with both cocaine use and firearms. New efforts must be made to decrease cocaine use and firearm availability. PMID- 8007080 TI - Graduate medical education reform. Service provision transition costs. AB - OBJECTIVE: To analyze the potential strategies and costs of house staff substitution under a reformed system of graduate medical education. DESIGN: An economic model using two scenarios for substitution of house staff (residents and fellows): (1) a lower-cost model under which nonphysician providers assume many house staff responsibilities, but additional aspects of their workload are taken over by staff physicians, nurses, and ancillary personnel; and (2) a higher-cost traditional model that relies more heavily on staff physicians to replace house officers. SETTING: US teaching hospitals. MAIN OUTCOME MEASURES: Projected net substitution costs of house staff on a per full-time equivalent basis and aggregate national cost estimates of substitution. RESULTS: Net annual house staff substitution costs were estimated to be $58,000 and $77,000 per replaced full-time equivalent house officer, respectively, under the two scenarios. Assuming elimination of approximately 23,200 house staff under a reformed system, total (net) substitution costs to teaching hospitals were estimated at approximately $1.4 billion to $1.8 billion nationally on an annual basis. CONCLUSIONS: Graduate medical education reform, while likely to result in substantial long-term cost savings, will necessitate transitions in service provision that are likely to generate some new costs in the short term. PMID- 8007081 TI - Treatment of malignant pericardial effusion. AB - OBJECTIVE: To discuss the diagnosis and treatment of malignant pericardial effusion and focus on quantitating the success and complication rates of the many treatment modalities and updating recent advances in the field. DATA SOURCES: English-language publications were identified by a computerized search (MEDLINE) of these key words: cancer, tumor, malignancy, pericardium, and pericardial effusion. This computerized search was supplemented by a manual search of the bibliographies of original research articles and textbooks. STUDY SELECTION: Studies were included if the outcome of patients undergoing treatment for malignant pericardial effusion was reported separately from the outcome of patients with other causes of pericardial effusions. Studies that only reported the combined results of patients with malignant and nonmalignant effusions were excluded. DATA EXTRACTION: To determine success rates for the various treatment modalities, we examined freedom from symptomatic recurrence of pericardial effusion requiring reintervention as the key end point. Where appropriate, we also examined procedural mortality rates. RESULTS: Initial relief of symptoms is achieved in most cases with percutaneous pericardiocentesis that, with echocardiographic guidance, can be performed with low morbidity and mortality. In many cases, drainage for several days with an indwelling catheter alleviates the effusion without subsequent recurrence. Systemic antitumor therapy with chemotherapy or radiation therapy is effective in controlling malignant effusions in cases of sensitive tumors such as lymphomas, leukemias, and breast cancer. Local sclerotherapy with tetracycline hydrochloride or bleomycin sulfate is also effective and associated with low morbidity. Sclerotherapy with other agents or radionuclides offers no advantages. Of the several surgical options, subxiphoid pericardiotomy has the advantage of low morbidity and mortality, can often be performed under local anesthesia, and is highly effective in preventing recurrence. Percutaneous balloon pericardiotomy has recently been described. This intervention is performed with local anesthesia, is effective in preventing reaccumulation, and has a low morbidity. CONCLUSIONS: Treatment of malignant pericardial effusions must be individualized with consideration given to the patient's condition and tumor type, the success rates and risks of the various modalities, and local availability and expertise. PMID- 8007082 TI - NIH Consensus Conference. Helicobacter pylori in peptic ulcer disease. NIH Consensus Development Panel on Helicobacter pylori in Peptic Ulcer Disease. PMID- 8007083 TI - A new agenda for women's health. PMID- 8007084 TI - The acid test. Making clinical sense of the Consensus Conference on Helicobacter pylori. PMID- 8007085 TI - Left ventricular mass and stroke. What is the connection? PMID- 8007086 TI - Studies question right heart catheterization. PMID- 8007087 TI - NIH panel report of 'no flaws' in FIAU trial at variance with FDA report, new probe planned. PMID- 8007088 TI - [Colony stimulating factors producing tumors]. PMID- 8007089 TI - [Non-small cell lung cancer]. PMID- 8007090 TI - [Human adjuvant disease]. PMID- 8007091 TI - [Diffuse alveolar damage]. PMID- 8007092 TI - [Diffuse pulmonary calcification, metastatic pulmonary calcification]. PMID- 8007093 TI - [Sinobronchial syndrome]. PMID- 8007094 TI - [Bronchorrhea]. PMID- 8007095 TI - [Honeycomb lung]. PMID- 8007096 TI - [Lesions of membranous bronchioles]. PMID- 8007097 TI - [Mucoid impaction syndrome]. PMID- 8007098 TI - [Squamous cell carcinoma (epidermoid carcinoma)]. PMID- 8007099 TI - [Melanocytic carcinoid of the lung]. PMID- 8007100 TI - [Benign metastasizing leiomyoma]. PMID- 8007101 TI - [Granular cell tumor (granular cell myoblastoma)]. PMID- 8007102 TI - [Mesenchymal tumor]. PMID- 8007103 TI - [Hemangiopericytoma]. PMID- 8007104 TI - [Hemangioma, hemangiosarcoma]. PMID- 8007105 TI - [Hemangioendothelioma]. PMID- 8007106 TI - [Lambert-Eaton myasthenic syndrome]. PMID- 8007107 TI - [Osteoma and osteosarcoma of the respiratory system]. PMID- 8007108 TI - [Neurofibroma, neurinoma]. PMID- 8007109 TI - [Histiocytic sarcoma]. PMID- 8007110 TI - [Pleomorphic lipoma]. PMID- 8007111 TI - [Elastofibroma, fibroma]. PMID- 8007112 TI - [Chondroma and chondrosarcoma of the respiratory system]. PMID- 8007113 TI - [Sclerosing hemangioma of the lung]. PMID- 8007114 TI - [Primary bronchopulmonary sarcoma]. PMID- 8007115 TI - [Myxoma of the lung]. PMID- 8007116 TI - [Lipoma and liposarcoma of the lung]. PMID- 8007117 TI - [Chemodectoma]. PMID- 8007119 TI - [Spindle cell sarcoma]. PMID- 8007118 TI - [Leiomyoma, leiomyosarcoma]. PMID- 8007120 TI - [Desmoid tumor]. PMID- 8007121 TI - [Benign clear cell tumor (sugar tumor)]. PMID- 8007122 TI - [Dumbbell neurogenic tumor]. PMID- 8007123 TI - [Endotracheal neoplasmas, endobronchial neoplasmas]. PMID- 8007124 TI - [Epithelioid hemangioendothelioma]. PMID- 8007125 TI - [Fibroleiomyomatous hamartoma, atypical lipomatous hamartoma]. PMID- 8007126 TI - [Lymphangioleiomyomatosis]. PMID- 8007127 TI - [Pancoast syndrome]. PMID- 8007128 TI - [Pulmonary hyalinizing granuloma]. PMID- 8007129 TI - [Malignant melanoma]. PMID- 8007131 TI - [Malignant paraganglioma]. PMID- 8007130 TI - [Atypical adenomatous hyperplasia]. PMID- 8007132 TI - [Xanthoma]. PMID- 8007133 TI - [Lymphangitis carcinomatosa]. PMID- 8007134 TI - [Carcinosarcoma of the lung]. PMID- 8007135 TI - [Tracheal tumor, bronchial and pulmonary tumor--epithelial malignant tumor]. PMID- 8007136 TI - [Trachial, bronchial and pulmonary non-epithelial tumors]. PMID- 8007137 TI - [Bronchocentric granulomatosis]. PMID- 8007138 TI - [Hamartoma, teratoma, dermoid cyst, embryoma, heteroplasia]. PMID- 8007139 TI - [Plasmacytoma]. PMID- 8007140 TI - [Plasma cell granuloma]. PMID- 8007141 TI - [Ectopic hormone producing tumor]. PMID- 8007142 TI - [Neuroectodermal tumor]. PMID- 8007143 TI - [Neurogenic tumors]. PMID- 8007144 TI - [Ganglioneuroblastoma]. PMID- 8007145 TI - [Metastatic cancer to the trachea, bronchus and lungs]. PMID- 8007146 TI - [Metastatic tracheobroncheal and lung sarcoma]. PMID- 8007147 TI - [Pulmonary blastoma]. PMID- 8007149 TI - [Pulmonary T cell lymphoma]. PMID- 8007148 TI - [Pulmonary malignant fibrous histiocytoma]. PMID- 8007150 TI - [Foreign body granuloma of the lung]. PMID- 8007151 TI - [Intrapulmonary lymph node]. PMID- 8007152 TI - [Paraffinoma]. PMID- 8007153 TI - [Cancer of the trachea and carina]. PMID- 8007154 TI - [Primary pulmonary paraganglioma and so-called minute pulmonary chemodectoma]. PMID- 8007155 TI - [Polypoid inflammatory pseudotumor (corpora amylacea pulmonum etc.)]. PMID- 8007156 TI - [Langerhans' cell histiocytosis]. PMID- 8007157 TI - [Langerhans cell granulomatosis (LCG)]. PMID- 8007158 TI - [Benign tumors of the trachea, bronchi and lung]. PMID- 8007159 TI - [Lymphocytic infiltrative lung disease]. PMID- 8007160 TI - [Lymphoproliferative disorder of the lung]. PMID- 8007161 TI - [Lymphocytic lymphoma, pseudolymphoma, benign lymphoma, lymphoid follicular hyperplasia]. PMID- 8007162 TI - [Epithelial tumors of the lower respiratory tract]. PMID- 8007163 TI - [Lymphomatoid granulomatosis]. PMID- 8007164 TI - [Epithelioid cell granuloma]. PMID- 8007165 TI - [Good syndrome: immunodeficiency with thymoma]. PMID- 8007166 TI - [Thymic carcinoid tumors]. PMID- 8007167 TI - [Thymic carcinoma, thymic adenosquamous carcinoma, thymic undifferentiated carcinoma]. PMID- 8007168 TI - [Thymic teratoma]. PMID- 8007169 TI - [Thymolipoma]. PMID- 8007171 TI - [Tumors of the thymus]. PMID- 8007170 TI - [Thymoma]. PMID- 8007172 TI - [Thymic cyst]. PMID- 8007173 TI - [Hodgkin's disease of the thymus]. PMID- 8007175 TI - [Castleman's disease]. PMID- 8007174 TI - [Invasive thymoma]. PMID- 8007176 TI - [Hamman syndrome]. PMID- 8007177 TI - [Acute mediastinitis]. PMID- 8007178 TI - [Malignant fibrous histiocytoma of the mediastinum]. PMID- 8007179 TI - [Bronchopulmonary carcinoid tumors]. PMID- 8007180 TI - [Mediastinal cavernous hemangioma]. PMID- 8007181 TI - [Mediastinal gas gangrene]. PMID- 8007183 TI - [Mediastinal teratoma]. PMID- 8007182 TI - [Bronchogenic cysts of the mediastinum]. PMID- 8007184 TI - [Mediastinal emphysema]. PMID- 8007186 TI - [Mediastinal goiter]. PMID- 8007187 TI - [Primary mediastinal choriocarcinoma]. PMID- 8007185 TI - [Angiomyolipoma]. PMID- 8007188 TI - [Mediastinal tumor]. PMID- 8007189 TI - [Bronchial adenoma]. PMID- 8007190 TI - [Mediastinal esophago-bronchogenic cysts]. PMID- 8007191 TI - [Mediastinal neurogenic tumor]. PMID- 8007193 TI - [Thoracic extramedullary hematopoiesis]. PMID- 8007192 TI - [Mediastinal neurinoma and neurofibroma]. PMID- 8007194 TI - [Mediastinal seminoma]. PMID- 8007195 TI - [Histoplasmoma]. PMID- 8007196 TI - [Mediastinal mesothelioma]. PMID- 8007197 TI - [Mediastinal endocrine tumor]. PMID- 8007198 TI - [Lung adenocarcinoma, Clara cell type]. PMID- 8007199 TI - [Mediastinal granuloma]. PMID- 8007200 TI - [Cystic hygroma of the mediastinum]. PMID- 8007202 TI - [Primary mediastinal germ cell tumors]. PMID- 8007201 TI - [Mediastinal cysts]. PMID- 8007203 TI - [Mediastinal parathyroid cyst]. PMID- 8007204 TI - [Mediastinal yolk sac tumor]. PMID- 8007205 TI - [Mediastinal malignant lymphoma]. PMID- 8007206 TI - [Mediastinal lymphadenitis]. PMID- 8007207 TI - [Neuroblastoma]. PMID- 8007208 TI - [Fibrosing mediastinitis, sclerosing mediastinitis]. PMID- 8007209 TI - [Cystic lymphangioma]. PMID- 8007210 TI - [Medullary carcinoma-like tumour of lung]. PMID- 8007211 TI - [Cheyne-Stokes respiration]. PMID- 8007212 TI - [CO2 narcosis]. PMID- 8007213 TI - [Wilson-Mikity syndrome]. PMID- 8007214 TI - [Phrenic nerve palsy (phrenic nerve injury, diaphragmatic paralysis]. PMID- 8007215 TI - [Diaphragmatic flutter]. PMID- 8007216 TI - [Respiratory failure in disorders of thoracic cage]. PMID- 8007217 TI - [Primary alveolar hypoventilation syndrome]. PMID- 8007218 TI - [Respiratory failure due to respiratory muscle fatigue]. PMID- 8007219 TI - [Respiratory failure due to respiratory muscle palsy]. PMID- 8007220 TI - [Respiratory failure (acute respiratory failure, chronic respiratory failure)]. PMID- 8007221 TI - [Respiratory distress syndrome]. PMID- 8007222 TI - [Sleep apnea syndrome]. PMID- 8007223 TI - [Juvenile papillomatosis]. PMID- 8007224 TI - [Adult respiratory distress syndrome (ARDS)]. PMID- 8007225 TI - [Pulmonary oxygen intoxication]. PMID- 8007226 TI - [Pulmonary encephalopathy]. PMID- 8007227 TI - [Alveolar hyperventilation]. PMID- 8007228 TI - [Alveolar hypoventilation]. PMID- 8007230 TI - [Obesity hypoventilation syndrome, Pickwick syndrome]. PMID- 8007229 TI - [Alveolar-capillary block syndrome]. PMID- 8007232 TI - [Behcet's disease]. PMID- 8007231 TI - [Lung cancer with calcification]. PMID- 8007233 TI - [Churg-Strauss syndrome]. PMID- 8007234 TI - [Progressive systemic sclerosis]. PMID- 8007236 TI - [Sjogren syndrome]. PMID- 8007235 TI - [Sarcoid angitis (nodular sarcoidosis, necrotizing sarcoid granulomatosis)]. PMID- 8007237 TI - [Still's disease]. PMID- 8007238 TI - [Adenocarcinoma]. PMID- 8007239 TI - [Wegener's granulomatosis, midline granuloma syndrome, lymphomatoid granulomatosis]. PMID- 8007240 TI - [Hypersensitivity angitis, small vessel vasculitis]. PMID- 8007241 TI - [Anklosing spondylitis]. PMID- 8007242 TI - [Primary anti-phospholipid syndrome]. PMID- 8007243 TI - [Collagen diseases]. PMID- 8007244 TI - [Pulmonary lesions in mixed connective tissue disease]. PMID- 8007246 TI - [Pulmonary manifestations in SLE]. PMID- 8007247 TI - [Temporal arteritis]. PMID- 8007248 TI - [Aortitis syndrome]. PMID- 8007245 TI - [Adenosquamous carcinoma]. PMID- 8007249 TI - [Pulmonary vasculitis]. PMID- 8007250 TI - [Pulmonary involvements in dermatomyositis and polymyositis]. PMID- 8007251 TI - [Lung diseases in rheumatoid arthritis]. PMID- 8007252 TI - [Cystine storage disease (Lignac-Fanconi disease)]. PMID- 8007253 TI - [Metabolic disorders of amino acids associated with respiratory distress]. PMID- 8007255 TI - [Alpha 1-antitrypsin (alpha 1-AT) deficiency]. PMID- 8007254 TI - [Adenoid cystic carcinoma]. PMID- 8007256 TI - [Glycogen storage disease]. PMID- 8007258 TI - [Mucopolysaccharidoses]. PMID- 8007257 TI - [Inborn error of lipid metabolism]. PMID- 8007259 TI - [Disseminated intravascular coagulation]. PMID- 8007260 TI - [Dressler's disease (intermittent hemoglobinuria)]. PMID- 8007262 TI - [Allergic purpura]. PMID- 8007261 TI - [Large cell carcinoma and variant (giant cell carcinoma, clear cell carcinoma)]. PMID- 8007263 TI - [Polycythemia vera]. PMID- 8007265 TI - [Storage pool disease (Hermansky-Pudlak syndrome etc.)]. PMID- 8007264 TI - [Pure red cell aplasia]. PMID- 8007266 TI - [Cryoglobulinemia]. PMID- 8007267 TI - [Pulmonary involvement in angioimmunoblastic lymphadenopathy]. PMID- 8007268 TI - [Primary macroglobulinemia]. PMID- 8007269 TI - [Pulmonary complications in myelodysplastic syndromes]. PMID- 8007270 TI - [Myeloid metaplasia]. PMID- 8007271 TI - [Multiple lung cancer]. PMID- 8007272 TI - [Adult T-cell leukemia, HTLV-I associated bronchopneumonopathy]. PMID- 8007273 TI - [Respiratory diseases in leukemia]. PMID- 8007274 TI - [Bare lymphocyte syndrome]. PMID- 8007275 TI - [Pulmonary lesions in AIDS]. PMID- 8007276 TI - [Carney's triad]. PMID- 8007277 TI - [Ehlers-Danlos syndrome]. PMID- 8007278 TI - [Hepatopulmonary syndrome]. PMID- 8007279 TI - [Hermansky-Pudlak syndrome]. PMID- 8007280 TI - [CA 19-9 producing lung tumors]. PMID- 8007281 TI - [Multiple cancer]. PMID- 8007282 TI - [Histiocytosis X]. PMID- 8007283 TI - [Kartagener's syndrome]. PMID- 8007284 TI - [Marfan syndrome]. PMID- 8007285 TI - [Ramsay Hunt syndrome; a special feature of acute respiratory failure]. PMID- 8007286 TI - [von Recklinghausen's disease]. PMID- 8007287 TI - [Rendu-Osler-Weber syndrome]. PMID- 8007288 TI - [Weber-Christian disease]. PMID- 8007289 TI - [Young's syndrome]. PMID- 8007290 TI - [Papilloma of the respiratory tract]. PMID- 8007291 TI - [Malignant histiocytosis]. PMID- 8007292 TI - [Graft versus host disease]. PMID- 8007293 TI - [Pulmonary involvement in inflammatory bowel disease]. PMID- 8007294 TI - [Yellow nail syndrome]. PMID- 8007295 TI - [Tuberous sclerosis]. PMID- 8007296 TI - [Primary ciliary dyskinesia]. PMID- 8007297 TI - [Sarcoidosis]. PMID- 8007298 TI - [Pulmonary lesion secondary to cardiac disorders]. PMID- 8007299 TI - [Renal disease]. PMID- 8007300 TI - [Renal tubular acidosis]. PMID- 8007301 TI - [Hypocomplementemia]. PMID- 8007302 TI - [Erythema infectiosum]. PMID- 8007303 TI - [Mucus-producing adenocarcinoma of the lung]. PMID- 8007304 TI - [Uremic lung]. PMID- 8007305 TI - [Cystic fibrosis]. PMID- 8007306 TI - [Mitochondrial disease]. PMID- 8007307 TI - [Immune compromised (acute necrotizing pneumonia, acute non-necrotizing pneumonia)]. PMID- 8007308 TI - [Ataxia-telangiectasia]. PMID- 8007309 TI - [Pulmonary complications of drug abuse]. PMID- 8007311 TI - [Straight back syndrome]. PMID- 8007310 TI - [Chest wall deformity]. PMID- 8007312 TI - [Mucous gland adenoma]. PMID- 8007313 TI - [Tumors of the diaphragm]. PMID- 8007314 TI - [Diaphragmatic hernia]. PMID- 8007315 TI - [Thoracic endometriosis]. PMID- 8007316 TI - [Thoracic outlet syndrome]. PMID- 8007317 TI - [Chest wall tumors]. PMID- 8007318 TI - [Chest wall abscess]. PMID- 8007319 TI - [Drug-induced interstitial pneumonitis]. PMID- 8007320 TI - [Pleuritis, pleural effusion]. PMID- 8007321 TI - [Respiratory neuromuscular dysfunction induced by drugs]. PMID- 8007322 TI - [Respiratory dysfunction induced by drugs]. PMID- 8007323 TI - [Pulmonary vascular disorders induced by drugs]. PMID- 8007324 TI - [Pulmonary hemorrhage]. PMID- 8007325 TI - [Mucoepidermoid carcinoma]. PMID- 8007326 TI - [Drug-induced pulmonary infiltration]. PMID- 8007327 TI - [Drug induced pulmonary edema]. PMID- 8007328 TI - [Obstructive pulmonary disease, bronchial asthma]. PMID- 8007329 TI - [Boerhaave syndrome (spontaneous rupture of the esophagus)]. PMID- 8007330 TI - [Congenital bronchopulmonary foregut malformation]. PMID- 8007331 TI - [Ectopic bronchus]. PMID- 8007332 TI - [Goodpasture's syndrome]. PMID- 8007333 TI - [Intravascular bronchioloalveolar tumor (IVBAT)]. PMID- 8007334 TI - [Marie-Bamberger syndrome]. PMID- 8007335 TI - [Cystic lesions of the trachea, bronchus and lung]. PMID- 8007336 TI - [Morgagni's hernia]. PMID- 8007337 TI - [Pulmonary leukoagglutinin transfusion reaction]. PMID- 8007338 TI - [Relapsing polychondritis]. PMID- 8007339 TI - [Swyer-James syndrome]. PMID- 8007340 TI - [T-lymphocyte alveolitis]. PMID- 8007341 TI - [Atrophic bronchitis]. PMID- 8007342 TI - [Inflammatory bronchial polyp]. PMID- 8007343 TI - [Cough syncope syndrome]. PMID- 8007344 TI - [Ventilation pneumonitis]. PMID- 8007345 TI - [Small cell lung cancer]. PMID- 8007346 TI - [Tracheobronchopathia osteochondroplastica]. PMID- 8007347 TI - [Tracheobronchomalacia]. PMID- 8007349 TI - [Broncholithiasis]. PMID- 8007348 TI - [Tracheobronchial amyloidosis, pulmonary amyloidosis]. PMID- 8007350 TI - [Bronchopulmonary dysplasia]. PMID- 8007351 TI - [Acute mountain sickness and chronic mountain sickness]. PMID- 8007352 TI - [Acute lung injury, chest trauma]. PMID- 8007353 TI - [Pulmonary hematoma]. PMID- 8007354 TI - [Intrathoracic kidney]. PMID- 8007355 TI - [Bronchioloalveolar carcinoma]. PMID- 8007356 TI - [Primary cavitary sarcoidosis]. PMID- 8007357 TI - [Destroyed lung]. PMID- 8007358 TI - [Restrictive lung disease]. PMID- 8007359 TI - [Syndrome of inappropriate secretion of antidiuretic hormone]. PMID- 8007360 TI - [Bronchiolo-alveolitis]. PMID- 8007361 TI - [Pulmonary oxygen toxicity]. PMID- 8007362 TI - [Postoperative pulmonary complications]. PMID- 8007363 TI - [Chronic lung disease in infancy]. PMID- 8007364 TI - [Congenital pulmonary lymphangiectasis]. PMID- 8007365 TI - [Alveolar cell tumor]. PMID- 8007366 TI - [Postperfusion lung syndrome]. PMID- 8007367 TI - [Centronuclear myopathy (myotubular myopathy)]. PMID- 8007368 TI - [Middle lobe syndrome]. PMID- 8007370 TI - [Granulomatous pneumonitis]. PMID- 8007371 TI - [Sudden infant death syndrome]. PMID- 8007369 TI - [Hyperlucent lung]. PMID- 8007372 TI - [Mucoid impaction]. PMID- 8007373 TI - [Pulmonary endometriosis]. PMID- 8007374 TI - [Cor pulmonale]. PMID- 8007375 TI - [Pulmonary Raynaud's syndrome (phenomenon)]. PMID- 8007376 TI - [Pulmonary hemosiderosis (idiopathic, secondary)]. PMID- 8007377 TI - [Pulmonary alveolar proteinosis]. PMID- 8007378 TI - [Pulmonary alveolar microlithiasis]. PMID- 8007380 TI - [Symptomatology and diagnosis of manic-depressive illness]. AB - Manic-depressive illness is recently named as a mood disorder according to the ICD-10 or DSM-III R diagnostic criteria. It consists of two opposite states, manic state and depressive state. Typical manic symptoms include a pathologic delightful mood, flight of ideas, heightened level of activity and sexual interest. Grandiosity, rapid and pressured speech, increased energy and decreased need for sleep are also frequently seen. On the other hand, depressive symptoms are characterized by prolonged depressive mood, inhibition of thought, lowered level of activity, depressive ideas or delusions and various somatic dysfunctions such as loss of appetite and sleep disturbance. Mood disorders are often seen in association with organic brain diseases, collagen diseases such as SLE, some endocrinological diseases and medication. Diagnosis of manic or depressive states is usually carried out by careful psychiatric interviews. No specific somatic symptoms or signs have been identified for manic-depressive illness. Many rating scales, for instance Zung's SDS or HDSR, have been utilized as diagnostic aids. Rating scales and the symptomatology and diagnosis of manic-depressive illness are described in general. PMID- 8007379 TI - [Affective disorders--concept, classification, and location in ICD-10]. AB - In 1899, Kraepelin, E. proposed the concept of affective disorder as "Das manisch melancholische Irressin". The classification of MDI had changed in several years. WHO developed the ICD-10 in 1990. In the F3 category of ICD-10, it is stated that MDI is a "mood (affective) disorder". In that category, there are seven categories which are divided in to several subclasses. The episodic mood disorders are "manic episode", "bipolar affective disorder", "depressive episode" and "recurrent depressive disorder". In contrast to these groups, the persistent mood disorders are "dysthymia" and "cyclothymia". In addition, there are two other items, "organic mood disorder" (F06.3) and "mixed anxiety and depressive disorders" (F41.2). PMID- 8007381 TI - [Analysis of plasma amino acids-tryptophan and tyrosine ratios to other large neutral amino acids in manic-depressive illness]. AB - On the basis of the hypothesis of the brain monoamine metabolism abnormality in manic-depressive illness, plasma tryptophan (TRP) ratio, an indicator of brain 5HT level, and the ratios of other neutral amino acids (tyrosine (TYR), valine, isoleucine, leucine, and phenylalanine) were determined in manic and depressed patients. Our results suggest that, in manic-depressive illness, there might be abnormalities in the metabolism of neutral amino acids, mainly of TRP and TYR, and that abnormality of TRP might be related to the depressive symptoms, and that plasma TRP and TYR ratios might be important indicators for determining the efficacy of some anti-manic and anti-depressive drugs. PMID- 8007382 TI - [Endocrinological examination and its clinical significance in manic-depressive illness]. AB - Neuro-endocrine test is one of the useful strategies in examining the pathophysiology of manic-depressive illness (MDI). Unfortunately, however, the pathophysiology of MDI has not yet been clarified and the specific biological markers of MDI have still not been found. In the present paper, a brief general survey as to main clinical points of endocrinological examination and its results towards the hypothalamic-pituitary-adrenal axis, the hypothalamic-pituitary thyroid axis, the hypothalamic-pituitary-gonadal axis, growth hormone, melatonin, etc. are given and some mentions of biological markers in MDI are made. PMID- 8007383 TI - [Computerized tomography of the brain in patients with affective disorders]. AB - In the past years, numerous papers of structural brain abnormalities which have been studied with computerized tomography scans (CT) in affective (mood) disorders have been reported. In this article, various CT findings in major depression and/or bipolar disorder are reviewed and the clinical significance of the brain structural findings are presented and discussed. PMID- 8007384 TI - [Magnetic resonance in patients with affective illness--relationship with silent cerebral infarction]. AB - We reviewed the relationship between affective disorder and magnetic resonance imaging (MRI). There are many reports that elderly patients with depression had increased small deep white matter lesions than the normal control. We examined silent cerebral infarction (SCI) in patients with presenile and senile major depression. Our findings suggest that half of presenile-onset major depression and the majority of senile-onset major depression might be organic depression related to SCI. Because patients with depressive states with SCI are at high risk of occurrence of stroke, we designated this condition "pre-stroke depression". It is important to begin therapy for cerebrovascular disease at this time. PMID- 8007385 TI - [Xe-133 inhalation single photon emission computerized tomography in manic depressive illness]. AB - We measured regional cerebral blood flow (rCBF) in depressed patients using Xe 133 inhalation single photon emission computerized tomography (SPECT; HEADTOME). Thirty-two medicated mildly depressed patients, six bipolar (BP) and 26 unipolar (UP), and 20 control subjects participated in the study. Compared to the controls, UP patients showed a significant decrease of rCBF in the bilateral frontal and the parietal regions, which were dominant in the left hemisphere, while BP patients showed no decrease of rCBF and mean CBF. Comparison of rCBF between before and after treatment with antidepressants in 8 depressed patients revealed an increased rCBF after the improvement in the left superior frontal, the left parietal and the right temporal regions which are critical areas for the development of depression. PMID- 8007386 TI - [Biological rhythm disturbances in affective disorders]. AB - Affective disorders are characterized by rhythmic disturbances: early morning awaking, diurnal variations in mood, and periodic and seasonal recurrence of episodes. Therefore, biological rhythm disturbances are considered as an etiology of affective disorders. The free-running hypothesis of cyclic mood disorders, or the phase advanced hypothesis, phase instability hypothesis, and reduced amplitude hypothesis of depression were formulated to explain a variety of clinical and physiological phenomena found in affective disorders. A new therapy such as chronotherapy has been developed according to the hypothesized mechanisms of biological disturbances. Furthermore, antidepressant effects of antidepressants, sleep deprivation, and phototherapy have been discussed from a chronobiological point of view. PMID- 8007387 TI - [Antidepressant and antimanic drugs--pharmacological mechanisms and pharmacokinetics]. AB - In Japan, fifteen drugs, including tricyclic and non-tricyclic antidepressants or an MAO inhibitor, are clinically available for treatment of depression. However, the pharmacological mechanism(s) of their antidepressive effect remain uncertain. "Receptor hypothesis" that functional changes of monoamine receptors after chronic treatment, such as down-regulation of beta-adrenoceptor or 5-HT2 receptor, bring about a therapeutic effect, seems to be unsatisfactory. Recent studies focus on interaction between antidepressants and intracellular signal transduction pathways. For effective and safe uses of antidepressants, especially in aged patients or those with hepatic and renal diseases, pharmacokinetics such as distribution, protein binding and metabolism must be well understood. In this paper, pharmacokinetic characteristics of antidepressants are also reviewed. PMID- 8007388 TI - [Adverse effects of antidepressants and anti-manics/mood stabilizers]. AB - Information on the adverse effects of antidepressants and antimanics/mood stabilizers is presented. The adverse effects of antidepressants include pharmacological side-effects, toxic effects, interactions with other drugs, withdrawal syndrome and "jitteriness" syndrome. The most common adverse effects with lithium treatment are polyuriapoly-dipsia, hypothyroidism, gastrointestinal symptoms, psychological complaints and ECG changes. The adverse effects of carbamazepine and valproate are mild and readily manageable, however problems associated with the hepatic system, the hematopoietic system and the thyroid gland, are important. It seems that no major deficits have been identified in studies of tricyclic antidepressant teratogenicity. Lithium, carbamazepine and valproate carry significant teratogenic effects. PMID- 8007389 TI - [World trends of new drug development for major affective disorders]. AB - No antimanic substance has been developed since lithium was introduced. There seem to be some anticonvulsant drugs which are considered to possess certain mood stabilizing effects similar to carbamazepine. There are a number of new compounds which are effective for depressed mood and induce a lower incidence of anticholinergic and cardiotoxic reactions than tricyclic antidepressants. Selective 5-HT reuptake inhibitors (SSRI) have been studied and some products have been launched in Europe and the US, but they are still under development in Japan. Selective and reversible MAO-A inhibitors may have an improved therapeutic effect. Other receptor agonists and antagonists may be usable in depressed patients who are resistant to, or intolerant of, other antidepressant therapy. PMID- 8007391 TI - [Drug therapy of manic-depressive disorders]. AB - Much more depressed patients visit general practitioners or internists than psychiatrists. Therefore, all doctors have to master the method how to treat depression. There are many cases who shift to protracted or chronic depression and intractable ones, because of insufficient medications. For example, antidepressants should be increased to the well-responded dosage, considering any side-effects, and should be continued till getting full recovery. On the other hand, manic patients should be treated by psychiatrists, because they usually lack the insight of disorders and refuse to receive any treatment. Most cases are obliged to hospitalize and to take mood stabilizers and sedative neuroleptics added on. PMID- 8007390 TI - [The treatments of manic-depressive psychosis]. AB - There are a number of types of treatment for manic-depressive psychosis, including pharmacotherapy, psychotherapy, electroconvulsive therapy and continuous sleep treatment. The most generally used therapy for mania is pharmacotherapy, including the use of lithium and major tranquilizers. With regard to depression, the choice of treatment from among pharmacotherapy, psychotherapy and physiotherapy must be made on a case by case basis. In some cases, we have chosen electroconvulsive therapy, continuous sleep treatment or other forms of therapy. On admission, it is difficult to obtain the patient's consent for treatment, when he lacks insight about his condition. In this paper, we describe the choice of treatments, requirements for admission, and management of the structure of treatment. PMID- 8007392 TI - [The treatment with Kampo medicine for manic-depressive psychosis]. PMID- 8007393 TI - [Psychotherapy for depression]. AB - This article aims at introducing recent psychotherapies for depression that have been developed mainly in the U.S.A., as well as delineating practical points of an integrated psychotherapy for depressive patients. First, cognitive therapy (Beck), problem-solving therapy, and interpersonal psychotherapy are reviewed. The author also briefly refers to psychodynamic psychotherapies and family therapies for depression. Second, the actual aspects of an integrated psychotherapy for depressive patients are delineated, according to the course of recovery. In addition, some treatment strategies for refractory depression are proposed. Finally, it is concluded that psychotherapy for depression requires both integrative and selective viewpoints, for application to each individual. PMID- 8007394 TI - [Sleep deprivation and continuous sleep treatment for depression]. AB - We explained about sleep deprivation (SD) and continuous sleep treatment (CST) such as nonpharmacological approaches for depression. Total sleep deprivation (TSD) showed dramatic, but transient, improvement in severe depression following one or more nights of SD. We reported the effects of TSD on 8 depressives. Consequently, after the TSD, the patients were divided into the groups of 3 responders and 5 non-responders in the score of on the basis of a 50% reduction in the score of Hamilton Rating Scale. The minimum rectal temperature (RT) of the non-responders was significant higher on the TSD night compared to the baseline night, but no significant change was observed in the responders. In addition, the minimum nocturnal RT of the responders before TSD tended to be higher. Nowadays, it is not so popular to use CST for depression because the technique is difficult. PMID- 8007395 TI - [Light therapy of patients with seasonal affective disorder]. AB - Numerous investigators have shown a strong association between the seasons and the incidence of depression, mania and suicides. However, little has been known about patients who reveal affective episodes in association with the changing seasons year after year. Lewy and Rosenthal established the concept of Seasonal Affective Disorder (SAD). SAD is characterized by recurring cycles of fall-winter depression and spring-summer hypomania (or euthymia). Depressive symptoms often include hypersomnia, anergia, fatigue, carbohydrate craving and weight gain. The syndrome occurs predominantly in women and begins in late twenties. Lewy, Rosenthal and other investigators found that exposure of the SAD patients to bright artificial light improved depressive symptoms. Some hypotheses of light therapy are proposed, however, each of them has not well explained the mechanisms. PMID- 8007396 TI - [Manic-depressive psychosis in childhood]. AB - In this paper, manic-depressive psychosis in childhood, in whom the age of onset was under 15 years old, is discussed. Firstly, I surveyed the history of studies in manic-depressive psychosis in childhood and dealt with the recent concept. Secondly, I reported the clinical features, such as classification, age of onset, sex, genetic factors, clinical symptoms, therapy and prognosis. Clinical study of 27 children who were diagnosed as mood disorders (manic-depressive psychosis) according to DSM-III-R is mainly cited. Finally, I emphasized the importance of physical symptoms and discussed the lower limit of age of onset. The problem of clinical entity, referring to schizophrenia and neurotic depression (dysthymia) in childhood, is discussed. PMID- 8007397 TI - [Presenile and senile affective disorders]. AB - The significance of endogenous factors becomes smaller and that of psychogenic or exogenous factors grows larger in affective disorders after the middle age. Psychogenic or exogenous factors include occupational factors, such as, retirement, familial factors, such as death of one's spouse, and independence of one's children, and somatic factors, such as ageing and somatic diseases. Atypical symptoms are more frequently seen than in the younger age. Somatic symptoms, hypochondriasis, agitation and paranoid are seen more frequently than in the younger age. On the other hand psychomotor inhibition is not so serious after the middle age. Masked depression, depressive pseudo-dementia and drug induced depressive state are seen more often, and they should be distinguished from somatic diseases and dementia. On manic state typical manic symptoms such as flight of ideas and manic excitement, are not seen so often as in the younger age. Adequate rest, medication and psychotherapy are necessary for the therapy of affective disorders. Considering pharmacokinetics in the elderly, anti depressants with less side effects should be chosen and they should be started from one-third of the regular dosage at most. PMID- 8007398 TI - [Refractory depression]. AB - It is generally accepted that antidepressants are ineffective in as many as 20 to 30 percent of patients with major depression. In Japan, the term "refractory" is commonly used to refer to a patient who does not respond to adequate treatment for depression, mainly standard pharmacotherapy. Factors associated with refractory depression are multiple. Refractory depression can be divided into several states, such as slightly depressive, neurotic, and residual. A variety of approaches to the refractory patient, that is pharmacotherapy, somatic therapy and psychotherapy is presented. PMID- 8007399 TI - [Delusional depression]. AB - Depression associated with delusion is generally called delusional depression from the clinical aspect. Since the introduction of tricyclic antidepressant for the treatment of depressive patients, it has been discussed whether delusional depression should be designated as a distinct syndrome or merely a severe variant of major depression. In this article, we reviewed the reports of studies, including ours, that have directly compared various factors of delusional and nondelusional depression to examine the validity of delusional depression as a clinical distinct entity. It may be given as a conclusion that delusional depression is a disorder that can be differentiated from nondelusional depression on many important dimensions, particularly suicidality, biological characteristics, clinical course, and therapeutic response. PMID- 8007400 TI - [Masked depression]. AB - Depressive disorders which masked by somatic symptoms is called masked depression. Masked depression is not a specific type of depression, but the general practitioners often misdiagnose it, because patients complain only somatic symptoms and most practitioners are not aware of it belongs to depression. Usually masked depression is mild, but is apt to chronic, and some patients become worse and might attempt suicide. The cause of depression is still obscure, but according to the results of many somatic tests, somatic findings are important. And differential diagnosis is also important. Concerning the treatment of mild depression, the patients dislike usual antidepressants because of the side effects. Then the author recommend to use a small dose of the drugs and some oriental herbal medicines. Oriental herbal medicines have fewer side effects, and effective for vegetative symptoms. PMID- 8007401 TI - [Postpartum depression]. AB - Depression following childbirth (postpartum depression) is a common psychiatric illness of women, postpartum. We review Japanese and English literature on postpartum depression. Problems with definition, study design and validity of the diagnosis prevented comprehensive understanding whether postpartum depression is a distinct subtype of endogenous depression. In general, postpartum depression seems to be the same illness as depression at other times in life. The biological and psycho-social pathogenetic factors, unique to the puerperal period, are not yet known. Clinicians caring for women and infants should learn to screen their patients for this multifactorial (genetic, temperamental, and environmental) disorder, and try to integrate a multidisciplinary (pharmaco-, psycho-, socio-, familial) approach. PMID- 8007402 TI - [Anxious depression and depressive neurosis]. AB - Among the diseases which, though demonstrating a depressive state, have anxiety symptoms in the foreground but are not accompanied by severe psychomotor retardation, include anxious depression and depressive neurosis. This report presents a general outline of anxious depression and depressive neurosis, together with their diagnosis, clinical features and therapy. In view of the expected continuing increase in the frequency of these two diseases in the future, the need for multidisciplinary approach, not only for the proper and early diagnosis, including differential diagnosis, and treatment of these diseases, but also for their prevention is described. PMID- 8007403 TI - [Adjunctive thyroid hormone therapy and comparison between responders and non responders]. AB - We review the theory and practice of adjunctive thyroid hormone therapy. Moreover, serum levels of thyroxine (T4), 3,5,3'-triiodothyronine (T3) and 3,3',5'-triiodothyronine (rT3) were examined in 8 depressed patients who did not maximally benefit from conventional antidepressant therapy. Four of the 8 depressed patients showed significant clinical improvement after thyroid hormone was added to their ongoing antidepressant drugs. T4 and rT3 levels prior to thyroid hormone supplementation were significantly lower in responders than in nonresponders, although within normal range. Furthermore, all of the patients who had both their rT3 levels less than 200 pg/ml and T4 levels less than 7 micrograms/dl responded to thyroid hormone treatment. These data suggest that lower T4 and rT3 levels can predict the treatment response to thyroid hormone supplementation in depressed patients. PMID- 8007404 TI - [The late-onset rapid cycling affective disorder]. AB - 166 depressive outpatients in Kurume University Hospital who were over sixty years old in 1993 were analyzed. Only 3 cases (1.8%) of the depressives were satisfied with the Dunner's criteria, which repeats affective episodes at least more than 4 times a year. Two of eight cases which were diagnosed the manic depressive illness satisfied the criteria. Most of the depressives were stable states and the depressive episodes did not change through one year. We presented a female case (aged 71), satisfying the DSM-3-R criteria for bipolar disorder. In this case, we monitored her polysomnography, and rectal temperature. Consequently this case showed remarkable changes in these parameters under manic, depressive and remissional phase, respectively. We conclude there are a few cases of the rapid cycling affective disorder over 60 years. PMID- 8007405 TI - [Manic-depressive states induced by drugs and various diseases]. AB - Manic-depressive states caused by drugs and various diseases consist of symptomatic psychosis, organic psychosis and toxic psychosis. Disturbance of consciousness is common to symptomatic psychosis. Emotional disturbance is associated with it. Dementia, personality change and disturbance of consciousness are common to organic psychosis. Emotional disturbance is also associated with these. Drug-induced manic-depressive states are classified by some studies. Drug induced manic-depressive states are often caused by drugs for physical diseases. They are not originally psychotropic drugs. And they have affinity to the central nerve system, to some degree. Interferons cause disturbance of consciousness or delirious state in the acute phase and depressive state or numerous psychiatric symptoms in the chronic phase. PMID- 8007406 TI - [Central nervous disease and manic state]. AB - We often observe several psychotic symptoms in physical illness-delusions, hallucinations, manic-depressive state and nervous state, for example. The purpose of this chapter is to account for the relationship between manic depressive state and central nervous disease. Secondary mania is considered to occur in association with physical illness. The criteria for a diagnosis of it is a duration of at least one week, elated or irritable mood, and at least two of the following: hyperactivity, "push of speech", flight of ideas, gradiosity, decreased sleep, distractibility, and lack of judgement. Depressive state is often observed in infarction, infection, neoplasm, head injury and degenerative disease. The differential diagnosis of pseudodementia and pseudodepression are receiving increased attention, we showed the table of clinical characteristics for distinguishing pseudo-depression from pseudodementia. PMID- 8007407 TI - [Manic-depressive symptom associated with endocrine and metabolic disorders]. AB - In an attempt to study "manic-depressive" affairs associated with endocrine and mental disorders, our clinical data are analyzed before and after appropriate treatment in Cushing's disease, Cushing's syndrome, hyperthyroid Graves' disease and primary hypothyroidism. Although our data do not provide definite findings on manic-depressive affairs associated with Cushing's disease and syndrome, review data by others indicated a high incidence of depression under untreated condition and its disappearance after appropriate treatment. In contrast, patients with adrenocortical insufficiency did have a depression but this was cleared after supplemental therapy. In hyperthyroid Graves' disease, a number of emotional and mental instability and irritability were noticed before the treatment, but these abnormalities all disappeared after appropriate treatment for 3-6 months. In contrast, patients with primary hypothyroidism did show lethargy and apathy, and these abnormalities disappeared after appropriate treatment. From the data accumulated, it is concluded that adrenal steroid and thyroid hormone do affect the functions of nervous system and, as a result, cause a number of clinical symptoms. The exact biochemical processes underlying these abnormalities are not known and remains for further investigations. PMID- 8007408 TI - [Collagen disease and vasculitis with manic and depressive symptoms]. AB - Collagen diseases and vasculitis diseases are known to have severe disorders in many organs. Manic and depressive symptoms are also found in these diseases as one of central nervous system disorders. They are frequently observed in systemic lupus erythematosus, primary Sjogren's syndrome and rheumatoid arthritis. It is very difficult to diagnose and treat the manic-depressive states because there are many origins that cause the psychological disorder; immunological disorders (anti-cardiolipin antibodies, anti ribosomal protein P etc.), cerebral vasculitis, thrombosis, infections, endocrinological disorders, steroid induced psychosis and so on. There are few pathogenic studies to explain the manic depressive symptom in these diseases. PMID- 8007409 TI - [A depressive disorder in patients with irritable bowel syndrome and non-ulcer dyspepsia]. AB - The relationships between psychiatric disorders and the symptoms of both irritable bowel syndrome (IBS) and non-ulcer dyspepsia (NUD) are herein investigated and discussed. Functional disorders of the small and large intestine induce irritable bowel syndrome. NUD is a syndrome that displays symptoms that might originate in the upper digestive system despite the absence of any organic disorder. In addition, it has also been suggested that the occurrence of NUD is based on a functional disorder of the upper digestive systems. Based on our studies of serious cases with both NUD and IBS, in approximately 50% of the NUD patients as well as about 50% of the IBS cases, a depressive disorder was found to be most closely related to the onset and continuance of the symptoms of either NUD or IBS. According to the evaluations of NUD and IBS as functional disorders and psychiatric disorders, the patients underwent treatment and all demonstrated a good response to the various treatment regimens. It is thus considered that NUD and IBS should be evaluated as both functional digestive disorders and psychiatric disorders. PMID- 8007410 TI - [Panic disorder]. AB - The recent publication of the Diagnostic and Statistical Manual of Mental Disorders, third edition (D.S.M-III) has provided the basis for the separate diagnostic entity of panic disorder. A panic attack is characterized by the abrupt onset of apprehension or fear accompanied by symptoms such as dyspnea, palpitation, chest discomfort, dizziness, sweating, feeling of unreality, and fear of dying. Panic disorder, defined as four panic attacks in a four week period, has a lifetime prevalence of 1 to 2 percent of the general population. In these patients, panic disorders can be provoked by pharmacological challenge with sodium lactate, yohimbine, caffeine and carbon dioxide inhalation. Recently, the relationship between panic disorder and depression became a subject of investigation from various points of view. PMID- 8007411 TI - [Chronic fatigue syndrome and psychiatric diseases]. AB - The chronic fatigue syndrome consists of a combination of non-specific symptoms. Some believe that the CFS is subcategory of major depression, because the symptoms are similar to those of major depression. We believe that the CFS is quite different from major depression or neurotic depression, since the CFS has no lack of initiative and effort, no inhibition which is seen in endogenous depression, and sharp fluctuations in general fatigue, anxiety, and various persisting somatic symptoms, such as, malaise and mild fever. CFS seems to be similar to the neurasthenia. It is harmful, at least, in aetiology and treatment, to neglect the diagnosis of the CFS. PMID- 8007412 TI - [Correlation of ill-defined syndrome with depression in the climacterium]. AB - The psychologic and somatic symptoms at climacterium are multiplicative, ill defined, and nonspecific. We studied 390 climacteric patients with ill-defined psychologic and somatic symptoms. While such symptoms arise from an estrogen deficient state of the menopause, these also occur in certain major psychiatric disorders, especially those of depression. Thirteen and twenty-one percent of the women were diagnosed as depression and masked depression, respectively. The incidence of generalized and panic disorder was 6.7% in each. The ill-defined syndrome of the menopausal age may be severe and persistent enough to meet the diagnosis of a major psychiatric illness, i.e. depression. As these disorders are important differential diagnoses, personality analysis and careful observation of clinical course may be indicated. Furthermore, the psychosomatic approach is recommended for all of these cases. PMID- 8007413 TI - [Alcohol dependence and affective disorders]. AB - The complex relationship between alcohol dependence and affective disorder has long been noted. Alcohol is capable of producing sadness in both alcoholics and nonalcoholics, but this sadness is time-limited and should not be confused with an affective disorder. Secondary alcohol dependence can occur in the midst of almost any psychiatric disorder. However, primary alcohol dependence with secondary affective disorder is not seen so often in inpatient alcoholics. There have been a large number of genetic-marker studies in the attempt to detect association and linkage with alcohol dependence, but there is no consistent evidence of genetic overlap between alcohol dependence and affective disorders. The administration of lithium may be useful in the treatment of alcohol dependence, but further research is required to determine whether lithium is useful in the treatment of depressive state of alcohol dependence. PMID- 8007414 TI - [Techno-Stress; techno-centered and techno-phobia]. AB - The "Techno-Stress" is a sociological new concept, hypothesized by Craig Brod and it includes clinically "Techno-Centered" and "Techno-Phobia". Based on 34 cases with mental disorders or psychosomatic diseases, we evaluated symptomatically these categories from standpoint of computer operating works. Fourteen cases represented severe problems in human relationship and they adapted excessively to computer operation. This group was thought as "Techno-Centered" and 50% of them were diagnosed as narcissistic, obsessive and schizophreniform personality. Twenty cases with maladaptation to computer operation were characterized as strict or avoidant personality and this group was evaluated as "Techno-Phobia". The "Techno-Phobia" was thought as simple adjustment disorder caused by new technology, on the other hand, the cases of "Techno-Centered" were seemed to be well-adapted to social skill only superficially, but psychological disturbance should be severer than "Techno-Phobia". PMID- 8007415 TI - [Borderline personality disorder]. AB - Although Borderline Personality Disorder (BPD) overlaps considerably with Major Depression, recent studies of biology, genetics and childhood trauma have demonstrated that there are substantial differences between the two disorders. It is suggested that their apparent relationship is rather nonspecific. In this paper, the author emphasizes that the core symptom of BPD is impulsiveness, which causes depressive symptoms and/or is induced by depressive episodes, forming a vicious cycle. Furthermore, in BPD patients, depressive symptoms are modified by impulsiveness, masochism, vanity, despair, and difficulties in interpersonal relationships. The author concludes that BPD is not a homogeneous but heterogeneous syndrome, classified into subtypes: depressive type, impulsive type, and identity diffusion type. Treatment needs to be considered according to these types. PMID- 8007416 TI - [Depression in the field of internal medicine]. AB - Masked depression is a common case of depression observed in the field of internal medicine. Masked depression redeems the organic disease alone, and so is often detected in the case of unidentified complaints. Symptomatic depression associated with the underlying disease is another type of depression that is commonly observed. In addition, there is the so-called "premonitory depression", which must be regarded as clinically important. This report describes our experience in the treatment of premonitory depression, with discussion on the consequence of manifestation of depression as the primary symptom of malignant tumor. PMID- 8007418 TI - [Management of depression at place of work]. AB - An outline is presented of depression and its management in a company, that is, early detection of depression, method of inducing workers to receive examination at the department of psychiatry, response to depressive patients, and evaluation of depression whether the worker is fit for reinstatement to former post. Management of depression in a company is based on clinical psychiatry, but under the present status, management of depression could not be conducted in an uniform pattern. Management of mental health with emphasis placed on the place of work and with consideration given not only to the individuality and sociopsychological aspect of each employee but also to the tradition of the company was found to be more readily accepted. It was observed that the company should also take into consideration not only depression but also more broadly the health of the mind. PMID- 8007417 TI - [Psychological test as a mass-screening system for depression]. AB - A mass-screening system for depression is aimed at calculation of the prevalence rate, or at mental health checks in employees. But with the recent increased interest in mental health and QOL, depression has become an important issue at every stage of the life cycle. In this paper, we review psychological screening tests for child, adult and aged from the viewpoint of life cycle. Some tests, especially for children and the aged need further tests regarding reliability and validity. What is clarified and which approach in mental health is indicated by the screening test must be further examined. Further development of screening tests, appropriate to each life cycle, is needed. PMID- 8007419 TI - [Early intervention and treatment of depressive and manic states among university students]. AB - Early intervention and treatment of manic and depressive states at university mental health service are described. Frequency of depression among the population of university students is about 0.1-0.2% and has increased during the last 10 years. The diagnoses of depressive states according to DSM-III-R are as follows; adjustment disorder with depressed mood (50%), major depression (20-30%), dysthymia (20%), and bipolar disorder (5-8%). Some plans for early intervention are discussed, including screening and consultation from the teaching staff and parents. Concerning treatment, it is important to support their academic problems caused by their mental disorders in close cooperation with their parents and their teaching staff. PMID- 8007420 TI - [Glomerular endothelial cell culture and its application]. AB - Glomerular endothelial cells (GEN) have recently been cloned, cultivated and characterized. They have as same biological characteristics as expressed in endothelial cells derived from different sources. Because of the difficulties of cloning of GEN, we first transfected plasmid DNA containing large T antigen of SV 40 (NH-GEN1). Culture method of GEN and NH-GEN1 and its application are discussed. PMID- 8007421 TI - Evaluation of biological characteristics of lung cancer by the human 28 kDa vitamin D-dependent calcium binding protein, calbindin-D28k. AB - We evaluated the biological characteristics of lung cancer by measuring their contents of human 28 kDa vitamin D-dependent calcium binding protein (calbindin D). Calbindin-D concentrations were determined in tumor tissue and normal lung tissue extracts from patients with lung cancer by enzyme immunoassay. The percentage of high calbindin-D containing tissues in small cell lung cancer (SCLC) was significantly higher than that in non-small cell lung cancer (NSCLC) and the calbindin-D concentration was low in normal lung extracts. In addition, most of the NSCLC which had a significantly high level of calbindin-D were at the advanced cancer stage with lymph node metastasis. Calbindin-D concentrations were also determined in lung cancer cell lines. The percentage of high calbindin-D containing cell lines was high in classic type SCLC, followed in order by variant type SCLC and NSCLC. In addition, in order to examine the usefulness of calbindin D as a marker of neuroendocrine properties of lung cancer, we compared the sensitivity and specificity of calbindin-D for distinguishing classic from variant type SCLC with neuron-specific enolase (NSE) and aromatic L-amino acid decarboxylase (AADC) by relative operating characteristic curves. The diagnostic accuracy of AADC was the highest of the three and that of calbindin-D was as high as that of NSE. These findings suggest calbindin-D to be related to the neuroendocrine properties of lung cancer. PMID- 8007422 TI - "Very well differentiated tubular adenocarcinoma" of the stomach: its endoscopic and histopathological characteristics. AB - Between 1986 and 1991, 31 patients having tubular adenocarcinoma with low cellular and structural atypism ("very well differentiated tubular adenocarcinoma:" tub 0) underwent surgery at the National Cancer Center Hospital (NCCH). Histologically, the 31 lesions in the 31 patients were very similar to those observed in gastric adenoma (World Health Organization) with severe atypism. Their malignancy could be diagnosed only on the basis of cellular atypism, i.e., uneven distribution of chromatin in the nucleus accompanied by irregularity in the size or shape of the spindle-form nucleus, abnormal nuclear polarity and/or obvious nucleoli. Histologically, the border between the tub 0 and adenomatous areas ('front line' of carcinoma) could not be identified within the neoplastic lesion, which showed relatively regularly shaped tubuli (less structural atypism). Of the 31 cases, 30 were solitary early gastric cancer (EGC). Their clinicopathological features were compared with those of 34 cases of gastric adenoma, 237 cases of solitary well differentiated (tub 1) and 127 cases of moderately differentiated (tub 2) tubular adenocarcinoma which had been resected at the NCCH during the same period. Most (75%) of the 30 tub 0 EGCs were type IIc (depressed) macroscopically, despite their histological similarity to gastric adenoma which showed a high (90%) elevated appearance incidence. The incidence of small lesions, < 2 cm in diameter, was highest in gastric adenoma (82%), followed by tub 0 (64%), although the tub 0 lesions showed a wide range of sizes. Small lesions were less frequent in the tub 1 (43%) and tub 2 (33%) cases. The incidence of submucosal invasion was significantly lower in tub 0 cases (17%) than in tub 1 (39%) and tub 2 (46%) cases (P < 0.05). No lymph node metastasis was seen in tub 0 cases, but was seen in 6.4% and 9.4% of tub 1 and tub 2 cases, respectively. With regard to the endoscopic appearance of depressed mucosal cancer, the incidence of encroachment (moth-eaten appearance) on the tips of folds was significantly lower (10%) and the appearance of marginal elevation was significantly higher (79%) in tub 0 than in tub 1 (each P < 0.05) or tub 2 (each P < 0.01). The results suggest that 'tub 0' can be regarded as a less malignant but not benign tumor, and that its endoscopic characteristics provide valuable information which can be used to ensure that patients receive suitable treatment. PMID- 8007423 TI - Relationship of ornithine decarboxylase activity and human colon tumorigenesis. AB - Ornithine decarboxylase (ODC) activity was determined in tumorous lesions of the human colon, and the possibility of ODC acting as a marker of colon tumorigenesis investigated. In adenoma, ODC activity, in pmoles/h/mg protein, was 164 +/- 82 in tumorous tissue, which was higher than the 19.6 +/- 10.5 in macroscopically normal mucosa (control tissue) around the tumorous tissue, while 8.7 +/- 4.1 in normal colon mucosa. In carcinoma-in-adenoma and carcinoma, ODC activities in the control tissue were 15.3 +/- 11.9 and 27.5 +/- 15.0, respectively. The levels were respectively higher than in normal tissue. These results suggest ODC to be a potential indicator of colon tumorigenesis. PMID- 8007424 TI - Proton beam therapy for patients with esophageal carcinoma. AB - Fifteen patients with esophageal carcinoma (superficial, six cases; advanced, nine cases) were treated with 250 MeV proton beam irradiation with or without external x-ray irradiation (12 MV linear accelerator) from October, 1985, to May, 1991. Eleven patients were initially treated with x-ray at doses of 16.2-50.4 (mean 42.5) Gy, followed by proton beam at doses of 30.0-52.9 (mean 37.6) Gy. The other four patients were treated with proton beams alone at total doses of 75.0 88.5 (mean 81.4) Gy. The mean total dose for the 15 patients was 80.4 Gy. As a result, the primary tumor lesions of all 15 patients disappeared and complete responses were obtained. Approximately four to five months later, nine of the 15 patients developed esophageal ulcer formations at the circumferences of their primary lesions. The ulcerations were healed, however, by conservative management. There was no evidence of local recurrence throughout the observations on six cases of superficial carcinoma. Among nine advanced carcinoma patients, three relapsed into esophageal carcinoma. Recurrences were observed eight, 16 and 44 months, respectively, after the treatment. Ten of the 15 patients died, but eight died of other diseases. Three of four cases at autopsy did not show any cancer cells in irradiated primary lesions. Four of the 15 patients lived for over five years. The results suggest that a high dose of irradiation delivered by a well-defined proton field could result in improved local control and long-term survival in esophageal carcinoma without undue risk of injury to primary and adjacent organs. PMID- 8007425 TI - Analysis of prognostic factors and chemotherapy of malignant fibrous histiocytoma of soft tissue: a preliminary report. AB - The inter-group study of malignant fibrous histiocytoma of soft tissue (MFH) was performed during the period January, 1988, to August, 1992 (4 yr 7 mo). There were 107 patients evaluated with an age range of 11 to 92 yr and an average age of 62.0 yr. There were 63 males and 44 females. The duration of follow-up was from 7 mo to 4 yr 5 mo with an average of 2 yr 6.2 mo. MFH occurred principally as a mass on an extremity (lower extremity 62%), upper extremity 18%, trunk 25%, head and neck 2%). It typically involved deep fascia or skeletal muscle (68%) or superficial subcutis (35%). There were 77 storiform-pleomorphic, 22 myxoid, three giant cell, two inflammatory and three angiomatoid variants. The absolute three year survival rate for all 107 patients was 72%. Patients with tumors located on extremities had a better three-year survival rate than patients with tumors located on the trunk or head and neck (81 vs 54%). There was, however, no statistical difference between the two groups. The prognosis for patients with deep muscular lesions, > 10 cm in diameter, was poor. The depth of the tumor significantly affects survival. The group with superficial tumors had a significantly better three-year survival rate than the other group (86 vs 68%). Local recurrences were found in 8% of patients who had had "complete" excisions. Inadequate surgery greatly increases the incidence of local recurrence and compromises longterm survival. Evaluations of tumor responses to preoperative chemotherapy and radiotherapy by histological studies were made. In total, 38 patients were evaluated. Responses to single and combination chemotherapy occurred in 31% of patients, a rate similar to that seen for other sarcomas. PMID- 8007426 TI - A case report of synchronous triple cancer resected simultaneously. AB - We report a unique case of a patient with synchronous renal cell carcinoma, hepatocellular carcinoma and squamous cell carcinoma of the oral floor. All three tumors were resected during a single operation. The patient was a 75-year-old man with masses in the liver and right kidney discovered by ultrasound examination during a routine checkup. Further examination also revealed a squamous cell carcinoma of the oral floor. The patient underwent a simultaneous radical nephrectomy, enucleation of the liver tumor and resection of the tumor of the oral floor. The diagnoses were histopathologically confirmed. The number of patients with multiple cancers has recently been increasing. The possibility of a second or third malignant lesion should be considered, not only in patients with a known malignancy but also in those without malignancy. The importance of screening procedures in the early detection of malignancy before the appearance of clinical symptoms should be emphasized. PMID- 8007427 TI - Malignant pheochromocytoma accompanied by microangiopathic hemolytic anemia: a case report. AB - A 63-year-old woman was in hospital for persistent backache. Four months prior to admission she had been pointed out as having hypertension for the first time. On admission, she had anemia (hemoglobin 7.0 g/dl) with reticulocytosis, and a blood smear showed fragmented erythrocytes. A bone marrow aspirate disclosed erythroid hyperplasia and invasion of cancer cells. The chest roentgenogram showed a coin lesion of the right lung and left pleural effusion. A diagnosis of microangiopathic hemolytic anemia (MAHA) associated with carcinomatosis was made, but the primary site of the cancer was unknown. Respiratory failure developed and the patient died a month later. Surprisingly, the autopsy revealed a malignant pheochromocytoma arising from the right adrenal gland with massive metastases to the lungs, liver, lymph nodes and systemic bones, and also disseminated intravascular coagulation (DIC). The DIC would probably account for the MAHA in this case. To our knowledge, this is the first reported case of malignant pheochromocytoma accompanied by MAHA. PMID- 8007428 TI - Carcinosarcoma of the ureter with unusual histologic features. AB - We report a rare case of carcinosarcoma of the ureter presented as a retroperitoneal tumor. The tumor originated in the ureter as a polypoid protrusion and spread around peri-ureteral, retroperitoneal tissues. The polypoid ureteral tumor was composed of an intra-epithelial carcinoma and a submucosal mesenchymal tumor; the histology of the retroperitoneal tumor in the original site was that of a carcinosarcoma. The bulk of the tumor in the retroperitoneum was composed of blastematous, epithelial and sarcomatous neoplastic cells with foci resembling an incomplete glomeruloid formation, thus mimicking a Wilms' tumor. The lesion appeared to originate from multipotential cells in the mucosal layer of the ureter. Whether or not this tumor has a true nephrogenic property is currently unknown. When a retroperitoneal tumor of the adult resembling a Wilms' tumor is found, one should suspect a possible carcinosarcomatous origin in the ureter. PMID- 8007429 TI - [The importance of the follow-up study on the retired workers--new aspects of the occupational health in our long lived communities]. PMID- 8007430 TI - [Comparison of matrix modifiers for simple determination of cadmium in blood and urine by graphite furnace atomic absorption spectrophotometry]. PMID- 8007431 TI - [Color vision among workers exposed to styrene]. PMID- 8007432 TI - [Determination of urinary metabolites of organic solvents among chemical industry workers]. AB - With the revision made to the Regulation on the Prevention of Organic Solvent Poisoning in June 30, 1989, analysis of urine must be made for metabolites as a part of the health examination of workers exposed to xylene, N,N dimethylformamide, styrene, 1,1,1-trichloroethane, tetrachloroethylene, trichloroethylene, toluene, and n-hexane. In accordance with this Regulation, health examinations were conducted at eight factories of five chemical manufactures in 1990. This report presents the results obtained for 1,073 workers as compiled by the Committee of Industrial Health of the Japan Urea and Ammonium Sulfate Industry Association. 1) The results of data analysis have shown that workers whose urine was collected when they had been exposed to an imperceptible degree to organic solvent or who underwent urine collection during an unknown period of time after exposure numbered 615 or 57.3% of all the workers. 2) Workers whose urine was collected within about 5 hours after exposure numbered 458 (42.7%). The metabolite concentrations in these workers were significantly lower than the BEI values. 3) It may be concluded from the results that workers were exposed to organic solvents to an extremely small extent during organic solvent handling operations at chemical industry factories which maintain good control over toxic materials. PMID- 8007433 TI - [Medical examination of workers exposed to lead in the Philippines]. AB - The medical examination of workers exposed to lead was conducted as part of the activity of the Occupational Safety and Health Center (OSHC) Project in the Philippines (JICA Project). The subjects of the medical examination were 21 male and 193 female workers of a semi-conductor plant (abbreviated A company), 59 male and 6 female workers of a refrigerator manufacture (B company); 199 male workers of a storage battery manufacturer (C company); and 107 male and 6 female workers of a lead smelter (D company). Among the examination items were questions regarding occupational history, subjective complaints and objective signs, determination of blood lead levels, urine delta aminolevulinic acid levels, and examination for anemia. The survey was conducted from June to September in 1990. The following results were obtained: 1) The mean age of the workers ranged from 21.8 to 33.8 years. Those of companies A and B were younger than those of companies C and D. The mean employment duration of males at C company was 10.7 yr, and the longest among the four companies. That in both sexes for A company was 1.8 yr and the shortest among the above mentioned companies. 2) The blood lead geometric mean levels of companies C and D showed the highest concentration. The level in males of C company was 64.5 micrograms/dl and that of D company was 80.8 micrograms/dl. The level in females of A company was 9.9 micrograms/dl and the lowest in concentration. The urine delta aminolevulinic acid geometric mean levels were less than 6.0 mg/l in the four companies. There was no company having hemoglobin mean values less than 14.0 g/dl in males or less than 12.0 g/dl in females. 3) The proportion of blood lead levels of 60 micrograms/dl or more was 67.3% in males of C company, and 89.7% in males and 16.7% in females of D company. The proportion of urine delta aminolevulinic acid levels of 6 mg/l or more was 1.0% in females of A company, 20.1% in males of C company, and 43.0% in males of D company. The proportion of hemoglobin values less than 14.0 g/dl in males or less than 12.0 g/dl in females was 4.7% in females of A company, 1.7% in males of B company, 3.5% in males of C company, and 12.1% in males of D company.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8007435 TI - Improvement of urinary delta-aminolevulinic acid determination by HPLC and fluorescence detection using condensing reaction with acetylacetone and formaldehyde. AB - We improved the method for determining urinary delta-aminolevulinic acid (ALA) by HPLC-fluorometer after pre-column derivatization with acetylacetone and formaldehyde, and a stable ALA derivative was obtained without any effect from various urinary components as demonstrated by the complete recovery of ALA (100.9 +/- 5.5%, n = 85) from the urine samples. The modified procedure was as follows: Twenty microliters of urine sample, 5 ml of acetylacetone solution (acetylacetone/ethanol/distilled water containing 4 milligrams of NaCl; 15/10/75), and 0.45 ml of 9.3% formaldehyde solution were mixed and boiled for 15 min. The fluorescent derivative of ALA was separated and analyzed by HPLC with the fluorometer at Ex 246 nm and Em 458 nm. Using a gradient program, the retention time of the ALA derivative was 7.3 min and the analysis could be repeated at 13 min intervals. Concentrations of ALA in urine samples measured by this method were significantly correlated with those measured by the Mauzerall Granick (M-G) method (n = 85, r = 0.993, p < 0.001). The values obtained by our method were, however, lower than those obtained by the M-G method. Urinary ALA concentrations of 40 non-lead workers ranged from 0.1 to 2.3 mg/g creatinine with the mean +/- SD of 1.1 +/- 0.4 mg/g creatinine as measured by the present method. PMID- 8007434 TI - [Actual status of measurement of blood concentration of lead, urinary concentration of delta-aminolevulinic acid and urinary concentration of metabolites of organic solvents entrusted to occupational health organizations]. AB - In Japan "the Regulation on the Prevention of Lead Poisoning" and "the Regulation on the Prevention of Organic Solvent Poisoning" were partially amended in 1989 to introduce biological monitoring in the special medical examinations of workers exposed to lead and 8 organic solvents (toluene, xylene, styrene, N,N dimethylformamide, n-hexane, tetrachloroethylene, 1,1,1-trichloroethane, trichloroethylene). Since many companies entrust these medical examinations to the Occupational Health Organizations (OHOs), a survey of OHOs which collect blood and urine samples for biological monitoring was made in August 1992, to ascertain the actual status of their activities from April of 1991 to March of 1992. The following findings were obtained through this survey. 1) One hundred and eighty-six OHOs collected 129,996 blood samples to measure the concentration of lead, and the median number of samples collected per organization was 356. 2) Thirty-nine OHOs (21.0%; Group A) measured all samples in their own laboratories. The number of samples measured was 55,462 (42.7%). However, 133 OHOs (71.5%; Group B) entrusted the measurement of all samples to registered laboratories. 3) The median number of samples collected by OHOs in Group A was 1,121, and the median number of Group B was 211. 4) One hundred and eighty-three OHOs collected 126,915 urine samples to measure the concentration of delta-aminolevulinic acid and the median number of samples collected per organization was 358. 5) The blood samples as well as the urine samples were divided into three groups according to the levels of lead or delta-aminolevulinic acid concentration. The concentration is relatively low in Group 1 and relatively high in Group 3. The cut-off values for this classification are legally set in the Regulation on the Prevention of Lead Poisoning. The frequency of each group was as follows: lead (Group 1; 93.8%, Group 2; 4.9%, Group 3; 1.3%), delta-aminolevulinic acid (Group 1; 96.8%, Group 2; 3.1%, Group 3; 0.2%).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8007436 TI - Effects of regular health practices on subjective evaluation of health. AB - The effects of Breslow's seven health practices on health were examined. The Today Health Index (THI), a questionnaire for self-evaluation of physical and mental health, was applied to male workers of a private company as well as their wives. The subjects resided in the suburbs of Tokyo and the average ages of the males and females were 41.5 and 38.4 years, respectively. Statistical results were obtained using Mann-Whitney U-test, analysis of covariance, and Hayashi's quantification theory I. A statistically significant decrease in the THI scale scores among subjects observing six or more health practices when compared with those observing three or less was demonstrated in vague complaints and irritability in males, and in respiration in females. In males, the THI scale scores of vague complaints, respiration, and the mouth and anus significantly decreased by sleeping well. Those of irritability and irregularity of life decreased by not smoking and those of vague complaints and irritability decreased by not eating between meals. In females, the THI scale scores of vague complaints, eye and skin, and the mouth and anus significantly decreased by exercising regularly. Those of irregularity of life decreased by not smoking. Those of respiration decreased by good weight control. Those of respiration and the mouth and anus decreased by not eating between meals. Exercising regularly in females was a good predictor of vague complaints using multi-variate analysis adjusted for age. Subjective evaluation of health improved by Breslow's recommended health practices. PMID- 8007437 TI - Analysis of acetone in urine by high-performance liquid chromatography. PMID- 8007438 TI - Background levels of total mercury concentrations in blood and urine. AB - We investigated the background levels of total mercury in blood and urine samples from Japanese subjects without occupational exposure to mercury vapor. Blood and urine specimens were decomposed in sealed Teflon containers, and total mercury concentration was measured by reductive vaporization-gold amalgam capture-atomic absorption spectrophotometry. The mean total mercury concentration in the blood of 56 women aged 34-65 was 18.2 +/- 9.9 ng/ml (range 3.9-56.8 ng/ml). The mean total mercury concentration in the urine of 130 men aged 22-39 was 2.33 +/- 1.50 micrograms/l (range 0.27-10.26 micrograms/l). The mean total mercury concentration in urine adjusted by specific gravity was 2.19 +/- 1.15 micrograms/l (range 0.68-7.68 micrograms/l), and that adjusted by creatinine was 1.51 +/- 0.68 micrograms/g creatinine (range 0.39-4.21 micrograms/g creatinine). These concentrations did not differ greatly from those reported from Europe and Japan. In expressing the total mercury concentration in urine, the creatinine adjusted range between the minimum and maximum values was smaller than the range adjusted by specific gravity. PMID- 8007439 TI - [Utility of multivariate analysis in evaluating the results of health examination on the basis of intra-individual variations]. AB - Utility of multivariate analysis in evaluating the values of laboratory tests on the basis of intra-individual variations (IV) was studied. Periodic health examination on workers has many clinical laboratory tests and these values are generally evaluated in comparison with "normal ranges." Recently it has been ascertained that the individual normal ranges were narrower than the populational normal ranges. Although the values of an individual should be estimated with normal ranges of the individual, it is almost impossible to determine the normal ranges from only one or two health examinations conducted per annum at the place of work. The author in his study could easily determine IV with a method using Mahalanobis' distance on a basis of populational normal range. In this method, if many values of a person in the tests vary in several years, the distance becomes larger, and if a value in a test falls outside the normal limit, it also becomes larger. This method makes it possible to detect not only an "abnormal" value out of the normal range but also a large value out of IV. To examine the practical validity of the method, the data of 24 employees (males, 45 to 65 years old) from 3 periodic health examinations and those of 20 persons (males, 48 to 71 years old) from 3 to 6 medical checkups were analyzed with regard to 11 items. It was found that 33 out of 44 persons were abnormal in one or more items and that 10 abnormal persons had large IV. They would be missed in the judgement with the use of only "normal ranges." As the distances were computed by a portable computer with a basic program, the method can be easily used in a small place of work. It is considered that this new method is effective and valuable not only as the screening procedure but also in the evaluation of IV. PMID- 8007440 TI - [Mental health and its related factors among middle-aged male workers: an eighteen-month follow-up study]. AB - Based on a longitudinal questionnaire survey of 11,121 subjects (males aged 30 59, engaged in various occupations and firms), this study examined the relationships of the baseline psychosocial work environment and personal health practices to mental disorders which occurred during an 18-month follow-up period. The onset of mental disorders during the follow-up period was assumed to be the time when the subject reported to have received medical treatment for the first time due to mental disorder. The psychosocial factors of the work environment were conceptually constructed from two aspects of working conditions and occupational stress. Working conditions were assessed by actual working hours, frequencies of late night work (10 p.m.-5 a.m.), and role in the organization. Occupational stress was measured by psychological work overload and job characteristics (job demands, decision latitude). Various factors associated with positive health behavior were examined through an index based on six variables, that is, supper time, exercise, smoking, alcohol consumption, sleep and weight. Multiple logistic analysis showed that both psychological work overload and late night work have a significant independent effect on the onset of mental disorders after controlling for other variables. PMID- 8007441 TI - Studies on cercariae from Kuwait Bay. V. Description and surface topography of Cercaria kuwaitae V sp. n. (Digenea: Heterophyidae). AB - A parapleurolophocercous cercaria, Cercaria kuwaitae V sp. n., was resembles closely larvae of the family Heterophyidae. Details are presented on the morphology, swimming activity and behavior of the cercaria. The surface topography of the cercaria and the redia was examined by scanning electron microscopy. PMID- 8007442 TI - DNA conformation polymorphism analysis of DR52 associated HLA-DR antigens by polymerase chain reaction: a simple, economical and rapid examination for HLA matching in transplantation. AB - HLA-DRB1 and -DRB3 alleles of DR52-associated (DR52ass) HLA-DR antigens were genotyped by a polymerase chain reaction (PCR) - based simple and practical method. Genomic DNAs from two hundred Japanese panels were subjected to PCR with two pairs of primers to separately amplify the DR52ass-DRB1 (DR3, 5, 6, and 8) alleles and DRB3 (DR52) alleles. The specific amplification revealed that 128 and 76 panels possessed DR52ass alleles and DRB3 alleles, respectively. PCR products from these panels were heat-denatured, electrophoresed in a non-denaturing polyacrylamide gel, and visualized by silver staining. Electrophoretic mobilities of the DNA samples were compared with those of the typing standards with known genotypes of DR52ass-DRB1 and DRB3 alleles. This method, designated PCR-DNA conformation polymorphism (DCP) analysis, allowed genotyping of the DR52ass-DRB1 and DRB3 alleles of panels without any sequence-specific oligonucleotide probe (SSOP) or restriction endonuclease, and the entire process after PCR could be completed within a few hours. Because the DR52ass-DRB1 and DRB3 alleles assigned by this method were shown to be identical to those determined by the PCR-SSOP method, PCR-DCP analysis was suggested to be a simple and practical HLA genotyping method. PMID- 8007443 TI - Comparison of hepatitis C virus strains obtained from hemodialysis patients. AB - To understand what genotypes of hepatitis C virus (HCV) exist in Taiwan, we chose the non-structure 5 (NS5) region of the HCV genome for the target area of reverse transcription-polymerase chain reaction (RT-PCR) to detect HCV RNA from sera of hemodialysis patients. Of 39 serum samples which were positive for the HCV antibody among 87 samples from hemodialysis patients, 12 (antibody against HCV core protein, OD > 2) were examined by the RT-PCR. The plasmid pUC19 was used to clone HCV cDNAs in the NS5 region (401 bp) derived from 11 serum samples which were positive for HCV RNA. Sequence analyses of individual clone of these 11 amplified cDNA fragments were performed. Dr. Cha's classification (16) suggested that two genotypes of HCV were found in these serum samples; type II (2/18.2%) and type III (9/81.8%). Our study indicates also that NS5 is an adequate target region to differentiate HCV strains derived from different patients in the same hospital. The analysis of the amplified cDNA in the NS5 region of the HCV genome will therefore provide suitable information to perform a molecular epidemiological study on the transmission routes of this important virus infection. PMID- 8007444 TI - Mechanisms of regulatory volume increase in collecting duct cells. AB - To examine the mechanisms of cell volume regulation in response to hyperosmolality, segments of the inner stripe of rabbit outer medullary collecting duct (OMCDi) were perfused in vitro. The cross-sectional area of the tubule was monitored as an index of the relative cell volume. When luminal and basolateral osmolalities were increased from 290 to 390 mOsm simultaneously, the tubule cell shrank instantaneously and reswelled gradually, showing the so-called regulatory volume increase (RVI). Basolateral Na+ removal and addition of basolateral ethyl isopropyl amiloride (EIPA) decreased the RVI response by 76 and 66%, respectively. By contrast, apical Na+ removal had no effect on this response. RVI response was also inhibited by basolateral, but not luminal, Cl- removal (-63%), by total HCO3- removal (-74%), and by adding basolateral 4,4' diisothiocyanostilbene-2,2'-disulfonic acid (DIDS) (-62%). Intracellular pH did not change significantly during RVI. Vasopressin increased RVI response by 56%. However, this increase was abolished in the absence of basolateral Na+ and Cl-, and in the presence of basolateral EIPA and DIDS. These results suggest that major mechanisms responsible for RVI are Na(+)-H+ and Cl(-)-HCO3- exchange systems in the basolateral membrane, and that these systems are stimulated by vasopressin in rabbit OMCDi. PMID- 8007445 TI - The staircase phenomenon and the strength-interval relationship of contractions in cultured cells of chicken embryonic ventricles. AB - The staircase phenomenon and the relationship between contraction strength and stimulation interval were investigated in single or aggregated cells cultured from 5-, 12-, and 19-d-old chicken embryonic ventricles. Within 24 h after start of cultivation was begun, the cells were separated and spontaneously inactive. However, they contracted when electrical stimulation was applied. The modes of a staircase phenomenon and a strength-interval relationship varied, depending on a few conditions such as the ages of the embryos, the presence of spontaneous activities and the composition of the bathing solution. The 19-d-old cells, which formed an aggregate and exhibited spontaneous activities, showed a negative staircase phenomenon and the negative strength-interval relationship when they were bathed in a culture medium containing bovine serum. The 12-d-old cells demonstrated a less distinct staircase and a flat strength-interval relationship. Both 19- and 12-d-old cells showed a positive relationship, if they were cultured for less than 48 h and were spontaneously inactive, or if they were bathed in Tyrode solution during the experiments. The 5-d-old cells showed the positive staircase whether they were spontaneously active or not. The developmental change in the interval-dependency of contraction can be explained by the functions of the sarcoplasmic reticulum (SR), although Ca2+ current and the Na(+)-Ca2+ exchange mechanism should be involved. The function of the SR develops progressively during the embryonic stage and plays an important role in regulation of the contraction-relaxation cycle at the late stage before hatching. PMID- 8007446 TI - Effect of dietary fat on glomerular lipid composition and angiotensin II receptors. AB - Nutritional factors are major etiologic determinants which may affect the incidence or severity of hypertension. Since angiotensin II (Ang II) has a role in some forms of hypertension, the influence of dietary lipid composition on glomerular lipid content and on Ang II receptor parameters was determined. Three groups of rats were fed diets containing 14% by weight of 1) beef fat (saturated fatty acid rich), 2) safflower oil (n-6 fatty acid rich), or 3) fish oil (n-3 fatty acid rich), each supplemented with 2% corn oil. A fourth group of rats was fed rat chow which contained 6.5% fat. At the end of 7 weeks, the rats were sacrificed, the kidneys removed, and renal glomeruli isolated using a sieving technique. Feeding diets which varied in the quantity and composition of fatty acids altered glomerular fatty acid composition of n-6 and n-3 fatty acids and the unsaturation indices of glomeruli. The cholesterol content, but not the phospholipid content, was decreased in glomeruli of animals fed the high fat diets. This resulted in a lower cholesterol/phospholipid ratio, indicative of an increase in membrane fluidity. Glomerular binding was determined using 125I-Ang II in a radioreceptor assay. Binding was proportional to glomerular protein and was time dependent. Receptor affinity (Ka) and number were determined by Scatchard analysis of binding inhibition data. Glomerular Ka was significantly lower for animals fed the rat chow as compared to the semisynthetic diets. There was no significant difference in the concentration of Ang II receptors in glomeruli of animals fed the different diets. The data indicate that the induced alteration in glomerular lipid composition is associated with alteration in the binding affinity of glomerular Ang II receptors. PMID- 8007447 TI - Blockade of sodium channels by divalent cations in rat gastric smooth muscle. AB - Using the whole-cell clamp method, the Na+ channel currents in smooth muscle cells of the rat stomach fundus were studied. After blocking K+ channel currents, step depolarizations from the holding potential of -90 mV induced fast activating, fast-inactivating inward currents (fast currents), which were followed by slowly-inactivating inward currents (slow currents). Using a nominally Ca(2+)-free bath solution, depolarization steps up to +20 mV induced only the fast currents, and depolarization steps to over +30 mV evoked outward currents. The fast current was inhibited by tetrodotoxin (TTX) or by removal of external Na+, thereby indicating that this was a Na+ channel current. The outward current was inhibited by nifedipine or by 0.1 mM Ca2+, thus, this current was a Cs+ current passing through Ca2+ channels. In the presence of 5 mM Ni2+, the Na+ current was reduced to about 15% of the control. When the rightward shift in the I-V relations was taken into account, the Na+ current was about 30% of the control. Mn2+ was less potent than Ni2+, and Cd2+ was more potent than Ni2+ or Mn2+, as a Na+ channel blocker. Plots of peak current amplitude, as a function of Cd2+ concentration, showed that one Cd ion was required to block one Na+ channel (KD: 55.7 microM). Thus, properties of the Na+ channel found in this smooth muscle cells are similar to those in vertebrate cardiac cells, in that the channel is relatively resistant to TTX and is sensitive to Cd2+. PMID- 8007448 TI - Changes in serum amino acid concentrations during prolonged endurance running. AB - Eight endurance trained distance runners (5 male and 3 female) ran on a treadmill at 60% of their VO2max for 3 h. Blood samples (about 12 ml) were taken immediately prior to the exercise, and thereafter every 30 min during and at the end of exercise. Urinary urea excretion was determined for the day of exercise, and for a control day a week after the exercise. Blood samples were analyzed for glucose, free fatty acids, urea and free amino acids concentrations. As the exercise was continued, there was a gradual decrease in the concentrations in serum of alanine and proline such that the concentrations of both the amino acids were significantly less at the end of exercise than the resting values (p < 0.01). These changes appeared to be highly correlated (r = 0.981, p < 0.05). The serum glucose concentration increased significantly (p < 0.05) after 30 min of exercise, remained significantly elevated until 150 min of exercise and then decreased to reach the resting value at the completion of the exercise. Serum free fatty acid (FFA) concentration was significantly higher at the end of exercise compared to the resting value. The increase in serum FFA concentration and the decreases in the concentrations in serum of alanine and proline were also found to be highly correlated (alanine versus FFA: r = -0.986, p < 0.05; proline versus FFA: r = -0.961, p < 0.05). The total urinary urea excretion (332 +/- 43 mmol versus 424 +/- 46 mmol) and urine volume (978 +/- 187 ml versus 1,480 +/- 245 ml) were less on the day fo exercise than on the control day. The decrease in urine volume was found to be significant (p < 0.05). PMID- 8007449 TI - Postnatal development of visual evoked potentials in Japanese black calves. AB - The visual evoked potential (VEP) was recorded in six Japanese Black calves from 1 to 10 weeks after birth. The VEP waveform recorded at the 1st week was consisted of three positive and three negative peaks. The VEP showed little postnatal changes except for the shortening of the peak latencies of P1 and N3 and the increase of the peak-to-peak amplitudes of P1-N1 and P2-N2 (significant between the 1st and 10th week of age). The visual function associated with generation of the flash VEP is suggested to have almost developed at birth in the calf. The postnatal measurement of the VEP would be useful for evaluating the neurologic disorders of the visual system in young calves. PMID- 8007450 TI - Exocytosis in the lingual mucus cells of Rana esculenta evoked by acetylcholine: observation of living cells by confocal laser scanning microscopy. AB - Exocytosis of a secretory cell is believed to occur when a part of the limiting membrane of the secretory granules fuses with the luminal plasma membrane to release their contents. Using a confocal laser scanning microscope, we have studied these events in living frog lingual gland cells. In a differential interference contrast (DIC) mode, secretory granules were found to be stable in general, but after stimulation with acetylcholine chloride (ACh) of more than 1 microM concentration, there were abrupt changes in the light intensity of granules as described in other cells. We found that with the same stimulation, two different types of secretion occurred. In the first type, a small vacuole was formed and granule contents were released from various regions of the cell. In the second type, a large vacuole was formed and granule contents were released all at once. Using two fluorescent dyes BCECF and Lucifer Yellow, we were able to perform positive and negative staining of the cell as well as its granules. Confocal images of the fluorescence mode clearly demonstrated the release process which corresponded to the DIC image observed simultaneously. The electron microscopic image also showed two different types of secretion. PMID- 8007451 TI - A closed chamber for intravital microscopy of the rat mesentery under controlled oxygen tension and temperature. AB - An airtight and watertight closed chamber for intravital microscopy of the rat mesentery was developed. It incorporates an oxygen microelectrode and a thermistor for monitoring the local environment around the mesentery, as well as a heater for controlling the chamber temperature. This chamber provides an alternative to the superfusion method for intravital microscopy of the mesenteric microcirculation under circumstances where well-defined experimental conditions are required. PMID- 8007452 TI - [Present status and future prospects of human gene therapy]. AB - Gene therapy is defined as the treatment of diseases by the transfer of genes into cells. This concept originally emerged as the definitive therapy for genetic disease. However, acquired diseases such as cancer and AIDS are now being considered as its potential targets. The first clinical trial of human gene therapy was in 1990 at the NIH in a 4 year old girl with fatal severe combined immunodeficiency caused by adenosine deaminase deficiency. Blood transfusion with genetically corrected lymphocytes resulted in significant improvement of the function of her immune system. The patient was discharged from hospital and is attending a public school. Immunotherapy for cancer using tumor cells transduced with genes for various cytokines and major histocompatibility antigens (tumor vaccine) has also been initiated at many research hospitals. In addition, gene therapy protocols targeting familial hypercholesterolemia, hemophilia B, cystic fibrosis are underway. Currently, more than 50 clinical protocols have been approved by the Recombinant DNA Advisory Committee at the NIH, and more than 100 patients have already been treated by this innovative therapeutic strategy. PMID- 8007454 TI - [Eosinophil and neutrophil degranulation in allergic inflammation: immunohistochemical localization of granule proteins in fatal asthma and stimulus dependent degranulation in vitro]. AB - Airway inflammation is a central feature of bronchial asthma. The eosinophil, a major infiltrating cell in the airway wall in asthma, expresses its effector function by degranulation of toxic granule proteins. The role of the neutrophil in allergic inflammation is still controversial. In order to clarify the possible involvement of degranulation in allergic inflammation, we studied the immunohistochemical localization of granule proteins of the eosinophil and the neutrophil, namely, major basic protein (MBP) and elastase, respectively, in the lungs from patients with fatal asthma. We found that extracellular deposition of MBP or elastase coexisted with epithelial damage in the airway and that more eosinophils were found in slow onset fatal asthma cases and more neutrophils in sudden onset fatal asthma. These results suggest that inflammatory cell degranulation may have induced tissue injury in cases of fatal asthma, and that there may be two pathologically distinct forms of fatal asthma in terms of involvement of eosinophils or neutrophils. Next we showed that IgA and IgG coupled to Sepharose beads induced eosinophil and neutrophil degranulation. IgA and secretory IgA (sIgA) for neutrophils and sIgA for eosinophils were the most potent stimulators of degranulation. Pretreatment of eosinophils with pertussis toxin (PTX) for 2 h irreversibly abolished sIgA-induced degranulation, whereas PTX treatment only transiently inhibited IgG-induced eosinophil degranulation. Activated PTX catalyzed the in vitro ADP ribosylation of 41- and 44-kDa proteins in eosinophils. A 2-h pretreatment of intact cells with PTX markedly reduced the pools of unmodified 41- and 44-kDa substrates available for subsequent ADP ribosylation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8007453 TI - [Recent progress in the use of the techniques in molecular histochemistry]. AB - Recent developments in molecular biology have made it possible to detect molecules such as mRNA and DNA in situ. In this report we focused on non radioactive in situ hybridization histochemistry using the alkaline phosphatase labeled oligodeoxynucleotide probe, which has recently been developed. We report the advantages of this method and some applications such as semiquantitative analysis and simultaneous demonstration of two mRNAs in a single section. In addition, vasoactive intestinal polypeptide (VIP) receptor mRNA was demonstrated in the lung as an application of in situ hybridization histochemistry in the field of thoracic diseases. We compared the localized of VIP mRNA-positive cells between normal animals and an animal mode of asthma. PMID- 8007455 TI - [Sleep-disordered breathing in Japan: an overview]. AB - Questionnaires were answered by 3,243 presumably healthy subjects who underwent regular medical checkups in four cities. The prevalences of risk factors for sleep-disordered breathing (SDB) were as follows; habitual snoring was reported by 13-16%, excessive daytime sleepiness by 8-9%, insomnia by 7-13% and systemic hypertension by 5-13%. Polysomnographic studies performed on some possible SDB cases who were selected by the presence of risk factors estimated that the average prevalence of SDB in the present population would be in the range of 1.14 1.94%. Secondly, questionnaires were sent to the main hospitals and institutes involved in the management of patients with SDB, asking about diagnostic criteria, number of SDB patients, management, effectiveness of treatment, etc. The total number of patients registered at those hospitals was 2,751 in 1991. Of the 132 patients who were followed for more than six months, the efficacies of body weight loss, medications, nasal CPAP and UPPP were compared. Based on the analyses of the 279 patients examined some tentative vriteria for diagnosis and for treatment are proposed. PMID- 8007456 TI - [Detection of IL-5 mRNA in bronchial biopsies from asthmatics by non-radioactive in situ hybridization]. AB - To determine whether IL-5 is locally produced in the bronchial mucosa of asthmatics, and to ascertain the precise cell type producing this cytokine, we examined bronchial biopsies by non-radioactive in situ hybridization and immunohistochemistry. IL-5 cDNA probes were labeled with digoxigenin-dUTP and hybridized to frozen or paraffin tissue sections. Hybridization signals were visualized by an immunohistochemistry technique. An IL-5-producing T cell clone derived from a patient with adult T cell leukemia was used as a positive control. Specific hybridization signals for IL-5 mRNA were observed in the bronchial mucosa of symptomatic asthmatics. No hybridization signal was detected in the control subject in whom no underlying disease was found. Immunohistochemical staining of serial sections using a panel of monoclonal antibodies directed against lymphocyte subsets strongly suggested that cells expressing mRAN for IL-5 were T cells. These results suggest that a cell-cell interaction between T cells and eosinophils through IL-5 may play an important role in the airway inflammation in asthma. PMID- 8007457 TI - [Superoxide dismutase suppressed asthmatic response with inhibition of manganese superoxide induction in rat lung]. AB - To investigate the involvement of oxygen radicals in the development of asthma, we examined the time course of changes in the expression of superoxide dismutases (SODs) both at mRNA and protein levels in the rat model of allergic asthma. We then examined the effects of recombinant-human SOD (r-hSOD) on these expressions and on the late asthmatic response (LAR). 1) In situ hybridization histochemistry and immunocytochemistry revealed that non-sensitized and sensitized rats before challenge had a very low level of manganese SOD (MnDOS) in the bronchial epithelial cells, although they showed a significant level of copper-zinc SOD (CuZnSOD). 2) All of the animals displayed LAR within 7 hours after the challenge, when they showed dramatic induction of MnSOD, but not of CuZnSOD, in the epithelial cells. 3) Treatment with r-hSOD almost completely suppressed LAR, with abolishment of MnSOD induction. This study suggests that the oxygen radical plays an important role in the inflammatory state of bronchial asthma, during which some cytokines induce the expression of MnSOD in the lung. PMID- 8007458 TI - [The role of mast cells and basophils in the pathogenesis of bronchial asthma]. AB - Bronchial asthma has now been recognized as an inflammatory disease. The present study was undertaken to evaluate the role of mast cells and basophils in the pathogenesis of bronchial asthma. Stem cell factor, a growth factor of mast cells, activates rat peritoneal mast cells and human lung mast cells to release histamine. We demonstrated the presence of basophils in lung tissues obtained from fatal asthma cases using immunohistochemical techniques. IL-3, GM-CSF, IL-5 and IGF-I enhanced basophil histamine release. These findings indicate that mast cells and basophils have important roles in the pathogenesis of bronchial asthma. PMID- 8007459 TI - [Bronchial asthma--airway inflammation and asthma--role of airway epithelium]. AB - The importance of airway inflammation in the pathophysiology of bronchial asthma has been recognized recently. This inflammation is organized by the interaction between inflammatory cells and the cells which compose airway structures. We studied the role of airway epithelium in airway hyperresponsiveness and airway inflammation, which are the major characteristics of bronchial asthma, and demonstrated a close relationship between them. On the bases of these data and the data reported by many other researchers, and from the point of view of airway inflammation, we discussed the possible roles of airway epithelium in bronchial asthma. PMID- 8007460 TI - [Role of eosinophils and lymphocytes in the pathogenesis of bronchial asthma]. AB - Lymphocytes and eosinophils are the two major inflammatory cells in the airways of patients with asthma. We studied the phenotypic composition and activation status of eosinophils and lymphocytes in bronchial biopsies obtained from asymptomatic and symptomatic asthmatics and nonasthmatic controls. The number of EG2-positive cells (activated eosinophils), CD3- and CD4-positive cells, and CD25 positive cells (activated lymphocytes) were significantly increased in the symptomatic asthmatics. In addition, significant correlations were noted between the density of CD4- and CD25-positive cells and the degree of eosinophil infiltration and activation. These data suggest that activated eosinophils and lymphocytes are involved in the pathogenesis of asthma and that activated helper T-lymphocytes play a central role in eosinophil infiltration and activation in the airways of asthmatics. Recently, eosinophil infiltration has been though to induce airway hyperresponsiveness by damaging airway epithelium through eosinophil granule proteins. To test this hypothesis, we investigated whether the number of clusters of desquamated respiratory epithelial cells in sputum is related to the eosinophil granule proteins in sputum and whether the ultrastructural changes in the bronchial epithelium are related to the presence of eosinophils in the bronchial mucosa. The results of both studies supported the hypothesis. PMID- 8007461 TI - [Role of adhesion molecules expression on eosinophils in bronchial asthma]. AB - Several characteristics of human eosinophil heterogeneity, as well as the existence of eosinophil subpopulations, "normodense" and "hypodense", have been reported in diseases associated with hypereosinophilia. Hypodense eosinophils can be distinguished by the increased expression of various membrane receptors including IL-5 receptor (J Exp Med 172: 1347) and various protein expression (J Immunol 142: 4416). On the other hand, recently, adhesion molecules are considered to play an important role in inflammatory processes in allergic and immune reactions such as bronchial asthma. Thus, in thin study, we examined the characteristics of expression of adhesion molecules on human eosinophils obtained from patients with hypereosinophila (hypodense eosinophils). As a result, high intensity expression of adhesion molecules (CR3, LFA-1 alpha, LFA-beta) on eosinophils were observed. Furthermore, ICAM-1, which is the ligand for LFA-1 molecules, was also expressed on eosinophils with hypereosinophilia. To extend our understanding of high intensity expression of adhesion molecules (CR3, LFA-1 alpha, LFA-1 beta, ICAM-1) on hypodense eosinophils, we examined whether chemotactic agents or eosinophilopoietic growth lymphokines (IL-3, GM-CSF, IL-5) are involved in adhesion molecule expression using an eosinophilic cell line, EoL 3. The expression of adhesion molecules on eosinophils was induced by some chemotactic agents and eosinophilopoietic growth lymphokines. Taken together, we conclude that eosinophilopoietic lymphokines as well as chemotactic agents may be involved in the high intensity expression of adhesion molecules on hypodense eosinophils.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8007463 TI - [Studies on biphasic animal model of asthma--lymphocytes and eosinophils]. AB - To clarify the role of lymphocytes and eosinophils in the late asthmatic response (LAR) observed several hours after OA challenge, and in airway inflammation observed 24 hrs after OA challenge in OA sensitized guinea pigs, we examined the infiltration and/or accumulation of lymphocytes and eosinophils in lung tissues by PKH2 labeling technique and Luna staining technique, respectively. The guinea pigs showed LAR 6 hrs after exposure to antigen, when moderate infiltration of lymphocytes and marked accumulation of eosinophils were observed in lung tissues. At 24 hrs after OA challenge, intensive infiltrations of both lymphocytes and eosinophils into the lung were observed. Pretreatment with MTX (methotrexate) suppressed LAR, inhibited infiltrations of lymphocytes and eosinophils into lung tissues at 6 hrs (LAR) and at 24 hrs after OA challenge, and prevented bronchial hyperresponsiveness to methacholine 48 hrs after antigen exposure in a dose dependent manner. These findings suggest that lymphocytes and eosinophils are involved in LAR and also in the chronic airway inflammation which is believed to make the bronchial asthmatic condition more severe and more refractory. Also, our results showed that MTX, which has an inhibitory action on such inflammation, may be a useful bronchial asthma. PMID- 8007462 TI - [Antigen-induced dynamic alterations of endothelin receptors--guinea pig lung tissues]. AB - Endothelins (ETs) are a family of peptides with potent constrictive activity in vascular and treacheal smooth muscle. The lung tissues are abundant in these peptides and their receptors; the peptides are produced by endothelial cells and airway epithelial cells, while its receptor is mainly located on smooth muscle. Therefore, it has been proposed that endothelins act in a paracrine fashion on nearby smooth muscle, thus regulating its tone. However, little is known about its physiological and pathological roles in pulmonary functions. We hypothesized that ET plays an important role in bronchoconstriction elicited by antigen challenge. In order to test this hypothesis, we investigated tracheal contractile activities and ET-receptors by employing an animal model in guinea pigs. Here, we report that guinea pigs who were sensitized followed by multiple challenges with the antigens had alterations of ET receptor(s) with respect to number and affinity. PMID- 8007464 TI - [Extended resection for lung cancer]. AB - Of the 740 patients with primary lung cancer operated on at our department between January, 1982 and December, 1991, 108 (14.6%) underwent extended operation involving combined resection of adjacent organs. The 5-year survival rates in patients who underwent resection of the parietal pleura (n = 62), thoracic wall (n = 25), diaphragm (n = 11), left atrium (n = 7), superior vena cava (n = 6), and aorta (n = 5) were 13.8%, 20.5%, 14.9%, 0%, 51.4%, 0%, and 20.0%, respectively. Surgical treatment for stage III advanced lung cancer is controversial, but the 5-year survival rates in those who underwent combined resection of the parietal pleura, thoracic wall including the ribs, left atrium, and aorta were not lower than that in all patients with stage III lung cancer. Especially, long-term survivals of 5 years and 11 months and 10 years and 6 months were obtained in patients who underwent resection of the left atrium, and 6-year survival was observed in a patient who underwent resection of the aorta, suggesting that extended resection is effective in some cases. The outcome of combined resection of the diaphragm and the superior vena cava was poor, with no patients surviving for 5 years. PMID- 8007465 TI - [Lung preserving operation for bronchogenic carcinoma--segmentectomy and bronchoplastic lobectomy]. AB - The results of segmentectomy and bronchoplastic lobectomy for bronchogenic carcinoma were reported. Until December 1992, 920 patients underwent lung resection for primary lung cancer at our institution. Among them, 70 patients (7.6%) had segmentectomy and 149 (16.2%) had bronchoplastic lobectomy. In cases with segmentectomy, adenocarcinoma (57.1%) and Stage I disease (77.1%) were dominant, and in cases with bronchoplasty, m squamous cell carcinoma (69.8%) and Stage IIIA (45.0%) were frequent. There were no operative deaths and one hospital death (1.4%) in patients with segmentectomy, and 8 operative deaths (5.4%) and 9 hospital deaths (6.0%) in those with bronchoplasty. Five-year survival rates of the patients with segmentectomy were 49.6% in total and 64.6% in those with Stage I disease. Five-year survival rates of those with bronchoplasty were 33.9% in total, 51.1% in those with Stage I, 29.1% in those with Stage IIIA and 39.0% in those with squamous cell carcinoma. Respiratory function was well preserved in patients with segmentectomy and bronchoplastic lobectomy. Lung-preserving operations such as segmentectomy and bronchoplastic lobectomy are meaningful as a curative procedure for primary lung cancer for selected patients. PMID- 8007466 TI - [Pathogenesis of idiopathic interstitial pneumonia/idiopathic pulmonary fibrosis: cellular and molecular biology of the disease]. AB - Idiopathic interstitial pneumonia (IIP), which is referred to as "idiopathic pulmonary fibrosis (IPF)" in US and European countries or "cryptogenic fibrosing alveolitis (CFA)" in UK, is considered to result from an uncontrolled, chronic inflammatory process in the lower respiratory tract and alveoli of the lung. It is conceivable that some hereditary background may contribute to the disease in susceptible individuals. In IPF, alveolitis involving activation of alveolar macrophages (AM), neutrophils, T- and B-lymphocytes and/or other inflammatory cell types precedes the injury to the lung parenchyma and interstitial fibrosis. Activation and accumulation of cellular components in the disease seem to be modulated by a variety of biological substances such as cytokines, chemotactic factors and adhesion molecules. Exposure to inorganic dusts or viral infection also may trigger activation of AM. The injury to the alveolar epithelium, capillary endothelial cells and extracellular matrix mediated by oxidants and/or proteases produced by AM and neutrophils results in the derangement of the lung parenchyma. Subsequent fibrotic change of the lung interstitium is characterized by the accumulation of mesenchymal cells such as fibroblasts and deposition of their connective tissue produces within the alveolar walls. In this process, AM is considered to play a major role by secreting growth factors for mesenchymal cells, although alveolar epithelial and endothelial cells also seem to participate in activating mesenchymal cell proliferation in IPF. Possibly, connective tissue synthesis and/or degradation may be altered in the process of IPF, although there is no direct evidence for this so far. Thus, IPF is a chronic inflammatory disease in which inflammatory processes of the alveoli injure the lung parenchyma and modulate the proliferation of mesenchymal cells which result in the fibrotic change. The pathogenesis of the disease involves multiple cellular components of the lower respiratory tract through modulation of gene expression and protein synthesis of a variety of biological factors. PMID- 8007467 TI - [A pilot study of induction chemotherapy with cisplatin, mitomycin C and vindesine for stage III N2 non-small cell lung cancer]. AB - PURPOSE: The postoperative survival of patients with preoperatively identified stage III N2 non-small cell cancer (NSCLC) is poor. A pilot study of induction chemotherapy consisting of cisplatin, mitomycin C and vindesine (CMV) was undertaken in an attempt to improve the curative potential of surgery in this group of patients. PATIENTS AND METHODS: Thirty-two patients with stage III N2a NSCLC received two cycles of CMV, (80 mg/m2 cisplatin i.v. on day 1, 8 mg/m2 mitomycin C i.v. on day 1, and 3 mg/m2 vindesine i.v. on day 1 and 8, every 4 weeks) preoperatively. The responding patients received a further two courses of CMV after surgery. RESULTS: The response rate was 63% (20 PR). All patients underwent operation including radical mediastinal node dissection. Twenty-six resections were curative and six were absolute non-curative. The toxicity was generally mild, but there were two hospital deaths, due to bronchopleural fistula and postoperative pneumonia. Sixteen patients have shown recurrent disease up to now. When the recurrence patterns were classified by clinical response, 11 responding patients were disease-free (9-84 months), but all non-responding patients had recurrent diseases. The median survival of curatively resected patients with pathological N2 was 39 months with a 5-year survival of 29%. CONCLUSIONS: This induction chemotherapy was well tolerated and revealed a high response rate. The current survival is obviously improved compared with the historical control, indicating that subsequent phase III clinical trials are urgently needed. PMID- 8007468 TI - [Radiotherapy and chemotherapy for locally advanced non-small-cell lung cancer: report of a clinical trial and review of the literature. South Osaka Lung Cancer Chemotherapy Study Group]. AB - A prospective nonrandomized phase II trial was performed from June 1989 to Oct 1990 using concurrent chemotherapy and split course radiotherapy in the treatment of inoperable, locally advanced non-small-cell lung cancer (NSCLC). Eligibility criteria consisted of NSCLC, inoperable stage IIIA or IIIB excluding T3N0 or T3N1 of TNM classification, with pleural effusion, age 75 y.o. or less, PS0-2, with measurable lesion, previously untreated, normal bone marrow, adequate renal and hepatic function, PaO2 > or = 70 torr, and with no other active neoplastic disease. Patients were treated with 50 Gy of radiation in 25 fractions to the chest, together with 100 mg/m2 cisplatin and 8 mg/m2 mitomycin-C on day 1 and 29 and vindesine 3 mg/m2 on days 1, 8, 29, 36. Sixty-five patients were entered into this trial and 61 were eligible. There were 4 ineligible patients (1 stage II, 2 stage IV, 1 malignant lymphoma). Fifty-seven patients received 2 or more courses of chemotherapy, with dose modification in 42 patients. Only 5 patients received less than 50 Gy radiation dose. Fifty-three patients had a partial response for an overall response rate of 87% (95% CI 78-95%). Median duration of response was 276 days. Median survival time (MST) was 450 days. One, 2, and 3 year survival were 60%, 37%, and 28%, respectively. In IIIa (13 patients), MST was 358 days and 1, 2, and 3 year survival were 50%, 50%, and 42%, respectively. In IIIB (48%), MST was 450 days and 1, 2, and 3 year survival were 63%, 33%, and 25%, respectively.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8007470 TI - [Phase II clinical trials in patients with lung cancer]. AB - The goal of phase II clinical trials is to determine whether a new drug has activity against particular cancers. This trial, therefore, is the most important study in the process of development of investigational new agents and frequently may give misleading results. The design of phase II clinical trials of new anticancer agents in lung cancer has been reviewed based on the Guidelines for the Clinical Evaluation of Antineoplastic Agents notified by the Ministry of Health and Welfare in Japan. These guidelines present general approaches to clinical trials and should be adhered to in the development of investigational drugs in humans, although they are not directly mandated by law or regulations. We considered the policies of these guidelines and instituted them based on the actual circumstances in Japan, in order to develop a scientific and rational approach for clinical phase II trials. In addition, we introduced new active agents having a novel mechanism of action that show clinical activity in the treatment of lung cancer, such as irinotecan (CPT-11), a topoisomerase I inhibitor, and paclitaxel (taxol) and taxotere, targeting the microtubules. PMID- 8007469 TI - [CAV-PVP chemotherapy and sequential thoracic irradiation (TI) for patients with limited (LD) small cell lung cancer (SCLC)]. AB - In order to assess the effectiveness of sequential TI for the treatment of LD SCLC, we analyzed 69 patients who had received CAV-PVP chemotherapy consisting of cyclophosphamide, adriamycin, vincristine, cisplatin and etoposide, plus sequential TI between 1986 and 1992. TI was delivered at a total dose of 50 Gy, 5 fractions/week for 5 weeks, once patients achieved a maximal response to chemotherapy. Responding patients also received PCI at a total dose of 30 Gy, 5 fractions/week for 3 weeks. Thirty patients achieved CR by chemotherapy and an additional 10 achieved CR after TI, resulting in a CR rate of 58.0%. Of 40 patients achieving CR, 24 have relapsed so far; the primary (in 15) and the brain (in 4) were the major sites of relapse despite TI and PCI. The median survival time was 18.4 months, with a 2-year survival rate of 39% and 3-year survival rate of 20%. Almost all the patients encountered grade 3 or grade 4 leukopenia while receiving chemotherapy, but the toxicity of TI was generally mild. This treatment is useful for patients with LD SCLC. PMID- 8007471 TI - [Interstitial pneumonia in patients with human T-cell lymphotropic virus type-1 infection]. AB - Pulmonary involvement has been demonstrated in patients with human T-cell lymphotropic virus type-1 (HTLV-1)-associated myelopathy (HAM/TSP) or with HTLV-1 uveitis. Pulmonary lesions in these patients are characterized by T-lymphocyte alveolitis. Interestingly, HLTV-1-infected cells were markedly increased in bronchoalveolar lavage fluid (BALF) obtained from patients with HAM/TSP and those with HTLV-1 uveitis compared to asymptomatic HTLV-1 carriers. Furthermore, the proportion of HTLV-1-infected cells was much higher in BALF than in peripheral blood. These results suggest that increased HTLV-1-infected cells play an important role in evolution of T-lymphocyte alveolitis associated with HTLV-1 infection. PMID- 8007472 TI - [Pathogenesis of idiopathic interstitial pneumonia: epidemiological approach from dust theory]. AB - In order to elucidate the factors relating to the pathogenesis of idiopathic interstitial pneumonia (IIP), an epidemiological analysis was carried out on 1880 autopsy cases of acute and chronic froms of IIP which were included in the Japanese Pathological Autopsy Records. The disease was found in a high frequency in high age groups, especially in males, and was more prevalent in agricultural than in urbanized districts of Japan. Studies on the occupational distribution demonstrated a significantly higher rate of the disease in the occupations in which workers might have been exposed to harmful dusts or fumes. Other studies on autopsy cases also reported a high incidence of IIP in occupationally exposed groups, and a clinical case control study again reported a high incidence of IIP in the occupational group including production metal workers. Together with the previous studies on element analysis of IIP tissue, exposure to harmful dusts including metallic compounds is a possible trigger, at least partly, for idiopathic interstitial pneumonia. PMID- 8007473 TI - [Causes of idiopathic interstitial pneumonia (IIP): inhaled dust as environmental problem]. AB - We have reported that patients with IIP can be roentgenologically grouped into two subtypes, typical (type-A) and atypical (type-B). The characteristic feature of X-ray findings in type-A is marked restriction of the lung, especially of the lower lobes, and in type-B is emphysematous changes in addition to the findings of type-A. In this study, to clarify the pathological findings of these two subtypes, 60 IIP patients in whom open lung biopsy and/or autopsy were performed were studied both clinically and pathologically. The following results were obtained. 1) Pathological features of type-A were alveolitis, marked restriction of the lung secondary to atelectasis and fibrosis of lung parenchyma, and honeycombing as a result of remodeling. 2) The features of type-B were intra alveolar organization and secondary emphysema after intra-alveolar inflammation (pneumonia) overlapped the pathological changes of type-A. 3) Patients with a history of dust inhalation were much more frequently observed in type-B than in type-A (p < 0.01). These results suggest that inhaled dust may be a causative factor of IIP, especially of type-B. PMID- 8007474 TI - [Pathogenesis of summer-type hypersensitivity pneumonitis]. AB - Summer-type hypersensitivity pneumonitis (SHP) is the most prevalent type of HP in Japan, and the major causative agent of the disease is T. cutaneum. The major antigenic substance of the yeast is serotype-related polysaccharide. Home environmental factors indicate that SHP is a sick house syndrome. Immunologically, both humoral and cellular hypersensitivities are involved in the induction of the disease. The levels of specific IgG and IgA antibodies and complements in BAL fluids from SHP patients are well correlated to the clinical course. On the other hand, BAL lymphocytes in SHP patients are mostly T lymphocytes, mainly due to an increase in CD8+ subpopulations of lymphocytes; this leads to a decrease in the ratio of CD4+ to CD8+. These T cells belong to CD45RO+ memory T lymphocytes and LFA-11 alpha high+ cytotoxic T lymphocytes as assessed by their cell surface phenotypes. However, functions of these BAL T lymphocytes remain undefined. Host factors such as HLA-DQw3 and cigarette smoking may participate in the development of the disease. In conclusion, the pathogenesis of SHP is considered to be a combination of immune complex disease and cellular hypersensitivity to T. cutaneum. PMID- 8007475 TI - [A study of interstitial pneumonia associated with collagen vascular disease- comparison with the data of idiopathic pulmonary fibrosis]. AB - To clarify the pathogenesis of idiopathic interstitial pneumonia (IIP), we compared the data of interstitial pneumonia (IP) associated with collagen vascular disease (CVD) with those of idiopathic pulmonary fibrosis (IPF). These disorders are found to have similar clinical, radiographic, and morphological findings, and lung function. However, the in vitro behavior of fibroblasts from CVD-IP and IPF, and the detection of soluble ICAM-1 were different. Further, in the T cell receptor repertoire, the predominance of different genes was found in bronchoalveolar lavage cells from CVD and IPF. These differences could partly explain the variability of IP pattern seen in CVD. In summary, our results indicate the possibility that CVD-IF and IPF result from different mechanisms although they share the same spectrum of pulmonary changes. PMID- 8007476 TI - [Chronic type hypersensitivity pneumonitis]. AB - The clinical features and chest X-ray appearances of chronic type hypersensitivity pneumonitis closely resemble those of idiopathic interstitial pneumonia. Therefore, it is very difficult to make a correct diagnosis without detailed information. Our study showed that bronchoalveolar lavage and lung biopsy are useful examinations for the differential diagnosis of these two diseases. The characteristic finding of bronchoalveolar lavage of chronic type hypersensitivity pneumonitis is still lymphocytosis, as is also seen in the acute type. The pathological findings of chronic type hypersensitivity pneumonitis are alveolitis with marked lymphocyte infiltrations and granuloma formation although the number of granulomas is low. Recently, we experienced five patients with chronic type farmer's lung. The average age of these five patients was significantly older than that of acute type farmer's lung. They had engaged in farming after the onset of their disease, which suggested continuous chronic exposure to mouldy hay. It is concluded that patients with hypersensitivity pneumonitis, especially aged people, should avoid antigen exposure and should be followed up the progress of the disease with intensive care. PMID- 8007477 TI - [Present world status and problems resolved in lung transplantation: from the surgical view]. AB - We have summarized the results of international data from many institutes. In 1983 in Toronto, Canada, Cooper performed that first successful clinical case lung-transplantation. Subsequently, there have been more than 1,500 cases of lung transplantation. One reason for Cooper's success was the use of cyclosporin, the other was the performing of omentopexy. Among the total lung transplant cases, single lung transplant comprised 66%, bilateral sequential lung transplant comprised 26%, and en-blocdouble lung-transplant, (8%). Of the 1,540 recipients, the most common underlying of sease was emphysema (360 cases), followed by fibrosis (289 cases), cystic fibrosis (206 cases), alpha-1 antitripsin deficiency (210 cases) and rare diseases including pulmonary hypertension, lymphagiomyomatosis and sarcoidosis. The survival rate of all patients was 68% at 1 year, and 60% at two years. PMID- 8007478 TI - [Selection of patients with UIP for lung transplantation]. AB - To select patients with UIP for lung transplantation, critical parameters that may indicate the prognosis after lung transplantation need to be found. We studied the course of disease of 53 cases of IPF which were diagnosed as UIP by open lung biopsy. We divided these cases into two groups: a decreased group in which the patients died due to the progression of the disease within two years after open lung biopsy, and a surviving group in which patients were still alive two years after biopsy. The comparative study revealed that there was no difference in symptomatic cases in the following parameters, the degree of the involved area on chest radiographs, a lower % VC and elevated LDH levels all related to the prognosis 2 years after open lung biopsy. However, there was no difference of the number of cases that satisfied all factors between the both groups. In conclusion, it is difficult to select recipients with IPF at an adequate stage for lung transplantation. Careful and intensive examination is required for selection of the recipients. PMID- 8007479 TI - [Projects in surgery for lung transplantation]. AB - Lung transplantation was simulated in 9 essential items in the surgical side. The possibility to utilize cardiac death donor instead of cerebral death donor was discussed. The transplant window was shown in a patient with primary pulmonary hypertension. The informed consent must be authorized at the specific meeting. For the pre- and postoperative care, it is essential for surgeon to treat on the team which is consisted of members from the specific regions. With donation, a method of the standardization for graft preservation was shown by statistical analysis of many factors. The level of surgical techniques in Japan have been evaluated to be on the current level. In postoperative care, reimplantation response, infection, and rejection are important factors which have been clinically overcome in preceding institutions. However, a practical method of established diagnosis for acute rejection remain unresolved. In addition, CMV infection will be an unavoidable problem in Japan. The research of immune tolerance has been successfully underwent in experiments to overcome chronic rejection. PMID- 8007480 TI - [The strategy how to restart heart transplantation in Japan from the viewpoint of cardiovascular surgeons]. AB - Japan is still in the midst of confusion the ethical, social and legal standpoints of organ transplantation. We have paid attention and effort to negotiate and reorganize the heart transplantation environment. This paper discusses several problems concerning the criteria, standardization, assessment, evaluation committee and authorization of medical centers to initiate heart transplantation in this country. PMID- 8007481 TI - [Organ transplantation and religious feeling of Japanese people against it]. AB - More than one year and six months have passed since the provisional committee on Brain Death has recognized brain death as the death of a human being, and the possibility of organ transplantation from the dead patient after brain death has been confirmed. However, no operation has been performed since then because of many obstacles. One of them is a cultural resistance which Japanese people have against the organ transplantation from a dead person whose heart is still beating. This resistance is based on religious feelings which have been cultivated through the long history of Japan. For opinion makers working professionally in the medical filed, what are the important points which should be examined in order to promote organ transplantation? In this paper or article, I will try to analyze this cultural and religious resistance against it. PMID- 8007482 TI - Assessment for pulmonary transplantation. PMID- 8007483 TI - Assessment of rejection and infection in post lung transplant patients. PMID- 8007485 TI - What's in a name? PMID- 8007484 TI - On leadership: lessons learned from geese. PMID- 8007486 TI - Therapeutic urine samples. PMID- 8007487 TI - More on management of patient with tricyclic overdose. PMID- 8007488 TI - Examples of critical paths for use in the emergency department. PMID- 8007489 TI - Munchausen syndrome: prevalence and intervention. PMID- 8007490 TI - Reminder to check febrile infants' fontanels during assessment. PMID- 8007491 TI - Supraventricular tachycardia in two adolescent patients. PMID- 8007492 TI - "Toxic strep" syndrome. PMID- 8007493 TI - Hand washing frequency in an emergency department. AB - Objectives Previous studies, conducted mainly in ICUs, have shown low compliance with hand-washing recommendations, with failure rates approaching 60%. Hand washing in the emergency department has not been studied. We examined the frequency and duration of hand washing in one emergency department and the effects of three variables: level of training, type of patient contact (clean, dirty, or gloved), and years of staff clinical experience. Design Observational. Setting ED of a 1100-bed tertiary referral, central city, private teaching hospital. Participants Emergency nurses, faculty, and resident physicians. Participants were informed that their activities were being monitored but were unaware of the exact nature of the study. Interventions An observer recorded the number of patient contacts and activities for each participant during 3-hour observation periods. Activities were categorized as either clean or dirty according to a scale devised by Fulkerson. The use of gloves was noted and hand washing technique and duration were recorded. A hand-washing break in technique was defined as failure to wash hands after a patient contact and before proceeding to another patient or activity. Results Eleven faculty, 11 resident physicians, and 13 emergency nurses were observed. Of 409 total contacts, 272 were clean, 46 were dirty, and 91 were gloved. Hand washing occurred after 32.3% of total contacts (SD, 2.31%). Nurses washed after 58.2% of 146 contacts (SD, 4.1%), residents after 18.6% of 129 contacts (SD, 3.4%), and faculty after 17.2% of 134 contacts (SD, 3.3%). Nurses had a significantly higher hand washing frequency than either faculty (p < 0.0001) or resident physicians (p < 0.0001).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8007494 TI - An observational study of the emergency triage nursing role in a managed care facility. AB - Introduction A 72-hour observational pilot study was conducted at a large managed care facility to determine what functions triage nurses fulfilled, how often they fulfilled these functions, and how much time was taken for these functions. Methods Patient arrival times, nursing activities, and patient dispositions were recorded. Activities were classified as either primary or nonprimary, according to defined triage purposes. Two alternating observers collected data continuously for 72 hours, during which they observed 13 triage nurses as they completed their regularly scheduled shifts. All nonprimary functions that occurred while the triage nurses fulfilled primary functions were classified as interruptions. All data were entered into computer software and whole minutes were used for calculating times. Results Nurses provided triage for 466 patients, and 655 telephone calls occurred. Twenty-nine physical triage activities and 26 telephone activities were observed. Telephone functions occupied about 22% of the time. Nonprimary telephone or triage functions interrupted 251 (54%) of all patients who were seen for triage. These interruptions notably increased pretriage waiting times for all patients who were interrupted but were most significant for patients with acuity levels 2 (p < 0.05) and 3 (p < 0.05). Number of interruptions and length of time spent waiting to see the triage nurses were significantly correlated (r = 0.69). Discussion Our study describes a method of evaluating triage nursing activities and suggests that some functions may contribute to delays in physician and nurse access. PMID- 8007495 TI - Emergency department nurse practitioners: the AtlantiCare Medical Center program in review. PMID- 8007497 TI - Nurse transport team. PMID- 8007496 TI - An emergency department telephone follow-up service. PMID- 8007498 TI - Management plan for a habitually combative patient. PMID- 8007499 TI - Mnemonics used for patient assessment. PMID- 8007500 TI - TAC (tetracaine, adrenaline, cocaine): a controversial topical anesthetic for suture of skin lacerations. AB - TAC and half-strength TAC appear to be highly effective and convenient local anesthetic agents that offer an advantage over injected lidocaine in acceptance by children. The use of TAC is not without risk (cocaine toxicity, theft, and abuse). The decision of whether to use TAC is usually made by the physicians in the emergency department, in conjunction with the pharmacy and therapeutics committee. If it is used, 2 to 3 ml of the half-strength TAC may be the safest dose. The emergency nurse must carefully apply the TAC to minimize systemic absorption and must monitor the patient for signs of any toxic effects. PMID- 8007501 TI - Trauma assessment suture treatment record. PMID- 8007502 TI - Special protocols for patients with trauma. AB - The ED care of the patient with trauma can be facilitated by the establishment of protocols to ensure prompt access to lifesaving and limb-saving procedures and care. Specific protocols for patients with trauma support assessment and treatment in both the emergency and long-term phases of care. PMID- 8007503 TI - CPR: computerized patient record. PMID- 8007504 TI - Blood alcohol tests in the emergency department. PMID- 8007505 TI - Developing self-teaching packages for the emergency department staff. PMID- 8007506 TI - Pertussis. PMID- 8007507 TI - Open pelvic fracture: the lethal injury. PMID- 8007508 TI - Syncope in an elderly woman. PMID- 8007509 TI - Nurses who served in Vietnam: silent heroes. Interview by Greg Gianas. PMID- 8007510 TI - The Old Emergency Nurse Reality Scale. PMID- 8007511 TI - In memoriam--to Sarah Kate: memories of your mom. PMID- 8007512 TI - Work redesign: an overview. AB - The process of redesign offers many opportunities to staff and leadership; it can be an exciting process with the potential for positive outcomes for staff, management, and patients. The key to success is to work together as a team to design new care teams and revised systems to enhance the quality of care provided. Changes will be and are taking place in health care. Nurses have the opportunity to use their creativity and innovation to help shape the future of health care. Emergency nurses can help accomplish this transformation and maintain our tradition as patient advocates for access to care and safe, quality patient care. This article has provided an overview of the major issues that should be addressed in a redesign project. Future articles will describe the redesign projects of specific emergency departments, highlighting strategies for planning and implementation. PMID- 8007513 TI - Quo vadis? PMID- 8007514 TI - Necessity of physician's signature on hospital medical records. PMID- 8007515 TI - The Canadian health care system: from masterpiece to mess. PMID- 8007516 TI - The Kansas Specific Health Plan. PMID- 8007517 TI - Pulmonary barotrauma in a mechanically ventilated patient with solitary head injury and no other predisposing factors. PMID- 8007518 TI - Needle localization of pulmonary nodule for thoracoscopic resection. PMID- 8007519 TI - [The clinical investigation of so-called "pleural tuberculoma" in the last 3 years]. AB - We have investigated on the clinical features of pleural nodular lesions which have appeared during chemotherapy of tuberculous pleurisy. Such lesions were observed in more than 10% of the cases of tuberculous pleurisy. This type of lesion occurred more frequently in the pleurisy patients whose chest X-ray did not show any tuberculous lesion in lung field and whose sputum was negative of tubercle bacilli. Most of the patients with such lesion were young. From these results, it was suggested that such lesion might develop during the course of primary tuberculosis. Single nodular lesion was more common but multiple nodular lesions were not rare. They had occurred in 2-4 months after the start of anti tuberculous chemotherapy including RFP, usually accompanied with chest pain. They had disappeared within 6-12 months without any additional therapy. In summary, pleural nodular lesions, which occurred during chemotherapy of tuberculous pleurisy, were not rare, but the clinical course and prognosis of such lesion were favourable and improved without any additional therapy. The etiology of such lesion has remained to be clarified. PMID- 8007520 TI - [Therapeutic potential of sparfloxacin for preventing mycobacterial infections]. AB - We studied the therapeutic potential of utilizing sparfloxacin (SPFX), a newly developed quinolone, to prevent various mycobacterial infections. The in vitro activity of SPFX as a preventive agent for various mycobacteria was determined using the actual count method on Ogawa egg medium. The minimal inhibitory concentrations (MICs) of SPFX were as follows: ofloxacin-sensitive M. tuberculosis, 0.16-0.32 microgram/ml; ofloxacin-resistant M. tuberculosis, 0.63 2.5 micrograms/ml; M. avium; 0.63-10 micrograms/ml (MICs were equal or less than 1.25 micrograms/ml in seven out of 11 strains); M. intracellulare, 2.5-10 micrograms/ml (MICs were equal or more than 10 micrograms/ml in 17 out of 23 strains); M. kansasii, < or = 0.08-0.16 microgram/ml; M. fortuitum, < or = 0.08 microgram/ml; M. chelonae subsp. abscessus, > 10 micrograms/ml; M. chelonae subsp. chelonae, 0.63 microgram/ml; M. scrofulaceum, < or = 0.08 microgram/ml; M. nonchromogenicum, 1.25 micrograms/ml; M. xenopi, < or = 0.08 microgram/ml; M. gordonae, < or = 0.08 microgram/ml. The average serum concentrations of SPFX during the period of multiple oral administration (200 mg once a day) were 0.35 +/- 0.16 microgram/ml before administration, 0.67 +/- 0.32 microgram/ml after one hour, 1.13 +/- 0.21 microgram/ml after two hours, 1.27 +/- 0.32 microgram/ml after four hours and 1.31 +/- 0.34 micrograms/ml after six hours. These results indicate that SPFX has a strong therapeutic potential to prevent infections due to M. tuberculosis, M. kansasii, M. fortuitum, M. chelonae subsp. chelonae, M. scrofulaceum, M. xenopi and M. gordonae. Moreover, it may be expected to be a promising agent against infections due to ofloxacin-resistant M. tuberculosis, M. avium and M. nonchromogenicum. PMID- 8007521 TI - [Home oxygen therapy in pulmonary tuberculosis and pulmonary atypical mycobacteriosis during chemotherapy]. AB - During the period of eight years from 1985 to 1992 we had sixteen patients (pulmonary tuberculosis: 6, atypical mycobacteriosis: 10) who had been under the treatment for tuberculosis and on whom home oxygen therapy (HOT) was started. Of sixteen patients twelve had history of antituberculous therapy in the past. There were nine chronic active or persistently sputum positive patients of whom three were pulmonary tuberculosis and six atypical mycobacteriosis. The duration of illness was long in these patients and it was more than ten years in tuberculosis patients. Four cases died, two cases of pulmonary tuberculosis died from hemoptysis, and two cases of atypical mycobacteriosis died from respiratory failure. PMID- 8007522 TI - [Responsiveness of lymphocytes from patients with M. avium-intracellulare complex (MAC) infection to PPDs as measured by IFN-gamma production]. AB - We investigated the responsiveness of peripheral blood lymphocytes (PBLs) from patients with M. avium-intracellulare complex (MAC) infection to the stimulation with PPDs by measuring their IFN-gamma producing ability. PBLs were obtained from MAC patients at active stage (culture-positive after three-month chemotherapy), those at inactive stage (culture-negative for three months after or during chemotherapy), and healthy donors. PPDs used were PPD-S prepared from M. tuberculosis, PPD-B from M. intracellulare, and PPD-Y from M. kansasii. PBLs from active MAC patients did not produce IFN-gamma to a significant extent by stimulation with any of three PPDs, while PBLs from inactive MAC patients showed higher responses to each PPD compared to those from active patients. In inactive MAC patients, the maximal response was observed to PPD-B among three PPDs. On the other hand, PBLs from healthy controls produced different levels of IFN-gamma in response to three different PPDs, and their response was most remarkable to PPD S. These results indicated that the responsiveness of patients' PBLs to PPDs was impaired during active stage of MAC infection and restored on recovery from the disease. PMID- 8007523 TI - [Two pulmonary tuberculosis cases with HIV infection]. AB - It was reported that HIV-infected persons were at much higher risk to develop active tuberculosis than HIV-none-infected persons, about 10% of whom might develop active tuberculosis through their lives, almost identical percentage of HIV-infected persons had developed active tuberculosis annually. In Japan, 2838 HIV-infected persons including 621 AIDS-cases were reported by the end of June 1993. Oct. Ten HIV-infected cases of active mycobacteriosis have been reported in literatures or on scientific meeting. We experienced two tuberculosis cases with HIV-infection recently and will report herein. FIRST CASE: A 23 years-old male student of Japanese-language school from Myammer. He was admitted to our hospital because of high fever and cough. His chest X-ray film taken on admission showed left hilar and mediastinal lymph nodes swelling, calcification of left hilar lymph node and infiltration in middle lung field. Sputum smear for acid fast bacilli was strongly positive. The cultured isolates were identified as Mycobacterium tuberculosis by DNA probe methods and were susceptibility tests were sensitive to all antituberculous drugs. Tuberculin skin reaction was negative. Laboratory data on admission: serum albumin level was 2.7 g/dl, A/G ratio was 0.75, CRP was 26.4 dg/ml, HBe antigen and antibody were positive, HIV antibody was positive by PA method and Western blot method, total lymphocyte count was 410/microliters, total T lymphocyte count was 303/microliters, total B lymphocyte count was 29/microliters, CD4+ T lymphocyte count was 37/microliters, CD8+ T lymphocyte count was 279/microliters, CD4+/CD8+ ratio was 0.1.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8007525 TI - [A book on old age: a story of a woman aged over 70 caring for her late husband's mother aged 95]. PMID- 8007524 TI - [Validity of "the risk index" to predict the infectiousness of tuberculosis patients]. AB - It has been proposed that "the risk index" obtained by multiplying the score of sputum-smear examination (Gaffky number) by the duration of symptomatic period in months is useful for the prediction of the infectiousness of a tuberculosis patient. To verify this theory, contacts examination of 498 index cases, who were newly registered by the Kochi Chuo Health Center from 1986 to 1988 as pulmonary tuberculosis patients, was carried out. Of the index cases, 58 cases (11.6%) were suspected to be responsible for significantly strong tuberculin reactions of one or more persons among their respective contacts. The proportion of such infectious cases was higher among the smear-positive index cases as well as those with cough, in comparison with smear-negative ones and those without cough. The rate of infectious case rose significantly according to the rank of "the risk index" of the index case. From these results, it was concluded that "the risk index" was useful to predict the infectiousness of the tuberculosis patients. PMID- 8007526 TI - [Report by director of nursing: hospice care and staff development]. PMID- 8007527 TI - [Medical topics: effect of decreasing number of children]. PMID- 8007528 TI - [Review of current health care systems: principle of costing in determining health care fees]. PMID- 8007529 TI - [Workshop for bone marrow transplant coordinator: bone marrow banks]. PMID- 8007530 TI - [Investigation of causes of nurses' malpractice: misconduct caused by too hasty or too narrow attention]. PMID- 8007531 TI - [The 1991 survey of hospital nursing personnel-III. Vacancy rates, recruitment and retention strategies, staff increase plan]. PMID- 8007532 TI - [Government-proposed 2-year correspondence course for assistant nurses to become nurses--JNA position against its introduction]. PMID- 8007533 TI - [National health care expenditure and international comparison]. PMID- 8007534 TI - [Development of doctor's program in nursing and the science of nursing in the United States]. PMID- 8007535 TI - [9th International AIDS Conference in Berlin]. PMID- 8007537 TI - [Consultation service by nursing personnel at outpatients clinic. Listening to and accepting patients' complaints]. PMID- 8007538 TI - [Consultation service by nursing personnel at outpatients clinic. Four public health nurses talk to patients in the home care service]. PMID- 8007536 TI - [Consultation service by nursing personnel at outpatient clinics. Caring and counseling alleviate patients' anxiety]. PMID- 8007539 TI - [Consultation service by nursing personnel at outpatients clinic. Support network developed for patients with rheumatoid arthritis]. PMID- 8007540 TI - [Consultation service by nursing personnel at outpatients clinic. Patients education by nurses in the outpatient clinic]. PMID- 8007541 TI - [Consultation service by nursing personnel at outpatients clinic. Nurses as resource persons for outpatients]. PMID- 8007542 TI - [Consultation service by nursing personnel at outpatients clinic. Increasing outpatient consultation and education in all departments]. PMID- 8007543 TI - [Consultation service by nursing personnel at outpatients clinic. Assisting patients and families for better self care]. PMID- 8007544 TI - [Consultation service by nursing personnel at outpatients clinic. Nurses as patient educator, care coordinator and practitioner]. PMID- 8007545 TI - [Visiting nursing service: organization and services of Wakabashi Visiting Nursing Station]. PMID- 8007546 TI - [Workshop for bone marrow transplant coordinator: history of bone marrow transplant]. PMID- 8007547 TI - [A book on old age: a movie The Company of Strangers]. PMID- 8007548 TI - [Report by director of nursing: function of nursing vs. function of family]. PMID- 8007549 TI - [Medical topics: on the degree program in nursing]. PMID- 8007550 TI - [Review of current health care system: pathology of team care]. PMID- 8007551 TI - [Visiting nursing service: management of service station]. PMID- 8007552 TI - [Visiting nursing service of San Mateo VNA, California]. PMID- 8007553 TI - [Current issues in caring for the elderly: the case of Ohme Keiyukai Hospital, a geriatric hospital of 788 patients, whose average age is 82.9 years]. PMID- 8007554 TI - [Literature search for nursing terminology: specialization in nursing]. PMID- 8007555 TI - [My consulting physicians and nurse]. PMID- 8007556 TI - [Discussion on the Report of the Ministry of Health and Welfare's Deliberative Committee on Nursing Service, a proposition to improve working conditions of nursing personnel]. PMID- 8007557 TI - [Discussion on the Report of the Ministry of Health and Welfare's Deliberative Committee on Nursing Service, a proposition to improve working conditions of nursing personnel. How working conditions have been improved at four hospitals designated as model hospitals to implement projects of better conditions--Hibiya Hospital, St. Luke's International Hospital, Kawakita General Hospital, Daiyukai General Hospital]. PMID- 8007558 TI - [Discussion on the Report of the Ministry of Health and Welfare's Deliberative Committee on Nursing Service, a proposition to improve working conditions of nursing personnel. The "Report" should place focus on patients]. PMID- 8007559 TI - [Discussion on the Report of the Ministry of Health and Welfare's Deliberative Committee on Nursing Service, a proposition to improve working condition of nursing personnel. Increased staffing level is the key to better nursing service]. PMID- 8007560 TI - [Discussion on the Report of the Ministry of Health and Welfare's Deliberative Committee on Nursing Service, a proposition to improve working condition of nursing personnel. Duties that have to be done by nurses]. PMID- 8007561 TI - [Discussion on the Report of the Ministry of Health and Welfare's Deliberative Committee on Nursing Service, a proposition to improve working condition of nursing personnel. Problems in nursing service and working conditions]. PMID- 8007562 TI - [Discussion on the Report of the Ministry of Health and Welfare's Deliberative Committee on Nursing Service, a proposition to improve working conditions of nursing personnel. Report of Deliberative Committee on Nursing Service]. PMID- 8007563 TI - Encouraging critical thinking in staff development. PMID- 8007564 TI - Enhancing critical thinking with questions. PMID- 8007565 TI - Promoting critical thinking. PMID- 8007566 TI - Common beginner mistakes with a computer. PMID- 8007567 TI - Ethics and health care reform. PMID- 8007568 TI - Preceptions on accreditation and licensure. PMID- 8007569 TI - Dietary protein alters tubular iron accumulation after partial nephrectomy. AB - Reactive oxygen species (ROS) have been implicated in progression of disease in the rat remnant kidney (RK) model of chronic renal failure. Substantial amounts of iron accumulate in proximal tubular lysosomes of RK and could damage tubules by ROS generation. The effect of dietary protein intake on ROS, tubular damage and iron accumulation assessed by energy dispersive analysis was determined in RK (5/6 nephrectomy, N = 12) and sham-operated kidneys (SO, N = 10). In RK, mean lysosomal iron concentration, urinary iron and protein excretion and morphological damage were increased and GFR decreased. Dietary protein loading (40% vs. 12%) increased the number of iron-containing lysosomes (P < 0.05) and the mean lysosomal iron (P < 0.02) in proximal tubular cells after four weeks. In RK, high protein diet increased renal weight (P < 0.01), numerical density of iron-containing lysosomes and tubular damage (both P < 0.05). ROS generation, assessed by tissue and plasma malondialdehyde (MDA), was also increased (both P < 0.05). Plasma MDA correlated with tubular iron accumulation (r = 0.75). In RK fed a high protein diet (N = 18) treatment with the iron-chelator desferrioxamine reduced serum iron, urinary volume, and tubular iron accumulation and damage compared to controls (P < 0.01). In summary, in RK dietary protein manipulation altered urinary iron and protein excretion, proximal tubular iron accumulation, renal cortical ROS generation and ultrastructural damage. Desferrioxamine treatment reduced tubular lysosomal iron and ultrastructural damage. These results suggest a role for tubular iron as a determinant of tubular injury associated with dietary protein loading in rats with partial nephrectomy. PMID- 8007571 TI - Regulation of calcitriol receptor and its mRNA in normal and renal failure rats. AB - Homologous up-regulation of calcitriol receptor (VDR) by calcitriol is believed to be a transcriptional event. In this experiment, we studied the effect of calcitriol on VDR in normal and renal failure rats. The time course of the effect of calcitriol on VDR mRNA showed a biphasic change in VDR mRNA in response to calcitriol. The concentration of intestinal VDR mRNA increased at six hours and reached peak levels approximately 15 hours after calcitriol injection. Thereafter, the mRNA began to decrease and by 48 hours the level had declined to below the control values. The VDR levels also increased, though they lagged behind the VDR mRNA, and nearly plateaued at 24 hours after calcitriol treatment. In renal failure, the concentrations of VDR were lower and the levels of VDR mRNA were higher than the respective values of normal rats, suggesting that VDR synthesis was inhibited at post-transcriptional sites. Chronic administration of calcitriol increased the VDR but lowered the VDR mRNA levels in both normal and renal failure rats. Infusion of uremic ultrafiltrate to normal rats resulted in lower VDR and higher VDR mRNA levels similar to those found in rats with renal failure. The results indicate that uremic toxins are responsible for the low VDR and high VDR mRNA in renal failure. PMID- 8007570 TI - The intensity of acidosis differentially alters the pathways of ammoniagenesis in LLC-PK1 cells. AB - Utilizing [5-15N] and [2-15N]-labeled glutamine and gas chromatography mass spectrometry methodology, we examined the pathways of ammoniagenesis under basal and acute acidotic conditions of pH 7.0 and pH 6.8, respectively. LLC-PK1 cultures were incubated for one hour with gentle rocking in a bicarbonate buffer of pH 7.4, pH 7.0, or pH 6.8 supplemented either with [5-15N] or [2-15N] glutamine at 37 degrees C in a 5% CO2/95% air incubator atmosphere. Incubation of cultures with [5-15N] glutamine at pH 7.4 resulted in a substantial amount of 15N ammonia formation which was not significantly altered by incubations at pH 7.0. By contrast, exposure to pH 6.8 significantly increased 15N ammonia formation in comparison with its production at pH 7.0 or 7.4. However, 15N ammonia production from [2-15N] glutamine was significantly stimulated at pH 7.0 and was further increased at pH 6.8. Incubation of the cells with [2-15N] glutamine resulted in a substantially lower amounts of 15N ammonia formation than produced with [5-15N] glutamine. Alanine formation from [2-15N] glutamine increased significantly at pH 7.0; but in contrast to 15N ammonia formation, pH 6.8 had no additional stimulatory effect on 15N alanine formation. Cells incubated with [2-15N] glutamine resulted in a significant decrement in 15N glutamate production at both pH 7.0 and 6.8 when compared with pH 7.4. 15N aspartate formation was unaltered by the changes in media pH.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8007572 TI - Epidermal growth factor antagonizes vasopressin in vivo and in vitro. AB - Since EGF causes diuresis through a renal action and may antagonize the hydroosmotic effect of AVP in vitro we investigated the antagonistic action of EGF with AVP in vivo and the mechanism of the antagonism in vitro. Conscious ewes received i.m. injections of a selective AVP V2-receptor agonist (1-desamino, D Arg8 vasopressin acetate, DDAVP) every 12 hours for days 5 to 16. All ewes received an i.v. isotonic saline infusion (100 ml/day) for days 1 to 8 and days 13 to 16, and i.v. EGF in 100 ml saline/day at doses of 0 (N = 8) or 10 (N = 8) micrograms/hr for days 9 to 12. DDAVP reduced both urine volume and water intake, and increased urine osmolality. In contrast, simultaneous infusion of EGF reversed the DDAVP-induced responses, resulting in a transient negative fluid balance, kaliuresis and a transient natriuresis (all P < 0.05). When EGF treatment ceased, the effects of DDAVP treatment alone gradually became apparent. From the in vitro studies, the AVP-related peptides displaced specific AVP V1- and V2-receptor antagonist radioligands from rat renal inner medullary membranes, whereas EGF had no effect. However, EGF antagonized AVP V2-stimulated cAMP production in a dose-dependent way (IC50 = 2 x 10(-7) M). Therefore, the diuretic effect of EGF is not via direct antagonism of the antidiuretic AVP V2-receptor but seems mediated by inhibition of the antidiuretic AVP V2-receptor second messenger system. PMID- 8007573 TI - Intracellular calcium concentration and activation of the Na+/H+ exchanger in essential hypertension. AB - To investigate the relationship between changes in intracellular calcium concentration ([Ca2+]i) and agonist-induced activation of the Na+/H+ exchanger in essential hypertension (EH), platelet [Ca2+]i and pHi were measured in 24 patients with EH (14 males) aged 48 +/- 2 years and 23 matched normotensive controls (NT) (12 males) aged 45 +/- 3 years. Measurements were done with spectrofluorimetry using the dyes Fura-2 for [Ca2+]i and BCECF for pHi. [Ca2+]i and pHi were measured in the resting condition and after stimulation in vitro with 0.1 U/ml human thrombin. The thrombin-induced rise in pHi was Na+ dependent and amiloride sensitive, indicating that it was mediated by the Na+/H+ exchanger. Unstimulated [Ca2+]i was higher in patients with EH than in NT (60 +/- 3 vs. 48 +/- 1 nmol/liter, P < 0.005), but there were no differences in resting pHi between both groups (7.16 +/- 0.01 vs. 7.16 +/- 0.008). In the presence of 1 mmol/liter external calcium (Ca2+o), thrombin-induced increment in [Ca2+]i was significantly greater in patients with EH than in NT (281 +/- 21 vs. 206 +/- 19; P < 0.05) as was the pHi increment (EH: 0.137 +/- 0.01; NT: 0.095 +/- 0.01; P < 0.05). Both agonist-induced increments in [Ca2+]i and in pHi were correlated with mean arterial pressure (MAP) only in the EH group (r = 0.58, P < 0.005 and r = 0.59, P < 0.005, respectively). The agonist-induced rise in pHi was positively correlated with the rise in [Ca2+]i both in the EH group (r = 0.65, P < 0.001) and in the NT (r = 0.55, P < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8007574 TI - Cell-mediated immune injury in the kidney: acute nephritis induced in the rat by azobenzenearsonate. AB - Cell-mediated immune mechanisms have long been suspected of playing an important role in the pathogenesis of various renal diseases. An animal model of active nephritis secondary to an exogenous antigen that requires antigen presentation to immune-competent T cells has not been developed. Consequently, the potential of kidney cells to serve as effective antigen presenting cells after an exposure to a therapeutic, biological, or environmental agent in the intact animal has not been documented. The present experiments were designed to demonstrate the capacity of the kidney to become the target for cell-mediated immune injury. A model system has been developed whereby a chemically reactive form of the hapten azobenzenearsonate is introduced directly into the left kidney of pre-immunized Brown Norway rats. Previous studies have shown that this form of the hapten requires active antigen presentation but no intracellular processing, since the reactive form of the hapten modifies directly surface expressed proteins. Delayed hypersensitivity was demonstrated in the actively immunized animals by standard lymphocyte stimulation index and by in vivo skin testing. Peak foot pad swelling of 220 +/- 13 x 10(-2) mm in response to the hapten was observed between days 11 and 14 as compared to < 10 x 10(-2) mm in the contralateral foot injected with vehicle alone and < 20 x 10(-2) mm in response to azobenzenearsonate injection in animals immunized with adjuvant alone. The exposure of the kidney to the hapten in the primed animal results in an active unilateral granulomatous nephritis with marked destruction of tubules and glomeruli. On average, 71.5 +/- 5.2% of the renal cortex is affected by the inflammatory process in the actively immunized animals, compared to only 8.1 +/- 3.8% in controls. The disease can be reproduced qualitatively by adoptive transfer of T cells but not by passive antibody administration to naive recipients. These studies demonstrate that intrinsic kidney cells can act as effective antigen presenting cells in the intact animal and that the kidney can become the target of a cell-mediated immune injury. PMID- 8007575 TI - Reactive oxygen species in puromycin aminonucleoside nephrosis: in vitro studies. AB - We examined the role of reactive oxygen species (ROS) in puromycin aminonucleoside (PAN)-induced changes to glomerular epithelial cells (GECs) in vitro. Levels of superoxide anion (O2.-), hydrogen peroxide (H2O2) and hydroxyl radical (HO.) were measured in rat kidney-slice cultures containing PAN with or without antioxidants (allopurinol, probucol and alpha-tocopherol/ascorbic acid). GEC morphology was assessed after three days of culture using transmission (TEM) and scanning (SEM) electron microscopy. The effects of hypoxanthine on GEC ultrastructure was also assessed. O2.-, H2O2 and HO. were generated when PAN was added to kidney-slice cultures in Medium 199. TEM morphometry revealed that incubation with PAN (100 micrograms/ml) significantly (P < 0.05 at least) retarded the loss of GEC foot processes normally seen in vitro. When the hydrophobic antioxidants probucol or alpha-tocopherol/ascorbic acid, which scavenged/inhibited generation of O2.-, H2O2 and HO., were added to cultures containing PAN, the effect of PAN on foot processes was abolished. The TEM appearance of GECs now resembled that seen in control cultures. On the other hand, SEM revealed that probucol and alpha-tocopherol/ascorbic acid provided no protection against the changes induced by PAN in GEC cell bodies or major processes. Allopurinol provided no protection against the changes induced by PAN in GEC cell bodies, major processes or foot processes. The addition of hypoxanthine to kidney-slice cultures did not result in the generation of O2.-, H2O2 or HO., or alter GEC ultrastructure. These findings indicate that ROS play a role in PAN-induced alterations to GEC foot process architecture in vitro. However, the xanthine oxidase pathway does not appear to play a major role in generating ROS from PAN in vitro. PMID- 8007576 TI - K(+)-sparing diuretic actions of trimethoprim: inhibition of Na+ channels in A6 distal nephron cells. AB - Hyperkalemia complicates trimethoprim-sulfamethoxazole (TMP-SMX) therapy in over 20% of HIV-infected patients. TMP is a heterocyclic weak base, similar to amiloride, a "K(+)-sparing" diuretic and Na+ channel blocker. Apical TMP is known to inhibit amiloride-sensitive short circuit current in A6 cells, a tissue culture model for mammalian cortical collecting tubule principal cells [1]. We used cell-attached patch clamp techniques to investigate the effect of TMP on the 4 pS, highly selective Na+ channel in the apical membrane of A6 cells grown on permeable supports in the presence of 1.5 microM aldosterone. Baseline channel activity at resting membrane potential, measured as NPo (N of channels x open probability), was 1.09 +/- 0.50 (N = 18). NPo (0.92 +/- 0.38; N = 9) was unchanged when 10(-3) M TMP was added to the basolateral bath for 30 minutes. However, apical exposure with pipettes containing 10(-3) or 10(-5) M TMP reduced NPo approximately tenfold (0.12 +/- 0.08; N = 7 and 0.18 +/- 0.14; N = 12, respectively). Kinetic analysis revealed the appearance of a new closed state after apical TMP treatment. Another group of A6 cells were pretreated with 10(-3) M apical TMP for 30 minutes prior to patching with pipettes filled with TMP-free saline. NPo progressively rose from 0.07 +/- 0.09 to 0.87 +/- 0.23 (N = 5) as the residual TMP was diluted within the pipette. Apical or basolateral pretreatment (30 min) with 10(-3) M SMX did not change Na+ channel activity.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8007577 TI - Extracellular matrix accumulation in immune-mediated tubulointerstitial injury. AB - The accumulation of excessive extracellular matrix (ECM) following tubular injury likely represents an imbalance between ECM production and degradation. We assessed the temporal relationship between the accumulation of ECM, cell adhesion molecules, matrix degrading proteinases, and their inhibitors in a rat model of anti-tubular basement membrane (TBM) antibody-associated tubulointerstitial nephritis (TIN) by the RNase protection assay and immunohistochemistry. There was an increase in the steady state expression of fibronectin (FN) and alpha 2(IV) collagen mRNAs beginning on day 7 with the onset of neutrophil infiltration. An increase in alpha 1(III) collagen and alpha 1-integrin did not occur until days 9 and 10, respectively, at which time mononuclear leukocytes were the predominant infiltrating cell. Increased levels of FN, alpha 1(III), alpha 2(IV) and alpha 1 integrin mRNAs occurred through day 14. By immunohistochemistry, increased accumulation of collagen IV, heparan sulfate proteoglycan, and laminin were detected along the thicken TBM; collagens I and III were immunolocalized within the tubulo-interstitium, while FN was present in both the TBM and interstitium in rats with TIN on day 14. The increase in matrix accumulation was associated with little or no increase in proteinases. u-PA transcripts fell beginning on day 8, with recovery to control values by day 12. Transin mRNA was found at low levels only on days 8 and 9, and the protein could not be detected by Western blotting. In contrast, these changes were associated with an increase in proteinase inhibitors, so that TIMP and PAI-1 mRNAs increased beginning on day 7 and persisted through day 14.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8007578 TI - Reduced hepatic growth hormone (GH) receptor gene expression and increased plasma GH binding protein in experimental uremia. AB - In uremia, reduced longitudinal growth and decreased hepatic insulin-like growth factor-I (IGF-I) secretion despite elevated GH serum levels point to an insensitivity to the action of GH. The molecular basis that accounts for this insensitivity could comprise decreased GH receptor expression in the target organs for GH or binding of GH in the circulation to substances that compete with the receptor. To address this hypothesis, the abundance of hepatic GH receptor mRNA was measured by solution hybridization RNase protection assay in uremic female Sprague-Dawley rats, following two-stage 5/6 nephrectomy, and in pair-fed and in ad libitum-fed sham-operated controls; rat GH binding protein (GHBP) plasma concentration was measured by a sensitive direct RIA. Uremia was associated with a 50% decrease of hepatic GH receptor expression compared to pair fed controls, which themselves showed a 25% reduction of hepatic GH receptor mRNA abundance when compared to ad libitum-fed controls. Plasma GHBP levels in uremia were markedly higher than in both control groups. Treatment with recombinant human GH (rhGH) (10 IU/kg body wt per day s.c. for 10 days) led to a comparable induction of IGF-I plasma levels and weight gain in uremia and pair-fed controls, indicating that the insensitivity to GH in uremia can be overcome by large rhGH doses. Subcutaneous rhGH injections did not significantly alter the hepatic GH receptor transcript abundance or plasma GHBP levels in any of the groups.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8007580 TI - B7(+)-transfectant tubular epithelial cells induce T cell anergy, ignorance or proliferation. AB - We have previously established that interferon (IFN)-gamma stimulated, antigen pulsed tubular epithelial cells (TEC) stimulate antigen (Ag) specific activation of T cell hybridomas to express IL-2. In contrast, these Ag pulsed TEC do not stimulate T helper 1 (Th1) clones to proliferate, but rather render them unresponsive, since Ag pulsed spleen cells cannot restore these cells to proliferate. The interaction of the T cell CD28 surface protein with its ligand B7 expressed on Ag presenting cells bearing Ia is a potent co-stimulatory signal capable of inducing T cell proliferation. Hence, the lack of B7 on TEC was hypothesized to be responsible for anergy in these Th1 cells. Therefore, the B7 gene was transfected into a SV40 transformed TEC or Chinese hamster ovary (CHO) cells, and created TEC and CHO cells expressing surface B7 protein. TEC-B7 (IFN gamma stimulated, Ag pulsed) express Ia and induce IL-2 production by T cell hybridomas. In contrast, T cell proliferation was not induced by TEC-B7 or CHO-B7 cells; however, these Th1 cells were not anergic since they could be stimulated to proliferate to Ag pulsed spleen cells (immunological ignorance). However, co cultivating TEC- B7 (IFN-gamma stimulated, Ag pulsed) with Th1 cells stimulated through the T cell receptor (TCR) using anti-CD3 monoclonal antibody (mAb) caused these Th1 cells to proliferate. Furthermore, anti-CD28 and anti-B7 mAbs blocked this response.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8007579 TI - Role of cytosolic Ca2+ and protein kinases in the induction of the hsp70 gene. AB - The role of cytosolic Ca2+ ([Ca2+]i) and protein kinases in the hsp70 induction following heat shock was investigated in cultured rat proximal tubular epithelial (PTE) cells. Changes in [Ca2+]i were measured by digital imaging fluorescence microscopy using fura 2. Steady state levels of hsp70 mRNA were examined by either Northern or dot blot analyses. [Ca2+]i increased within 10 minutes and continued to increase following heat shock. The increases in [Ca2+]i were reduced in nominally Ca(2+)-free media with or without EGTA. [Ca2+]i also increased within 0.5 minutes following ionomycin, but then declined to normal levels by 1.0 to 1.5 minutes. Heat shock induced hsp70 mRNA within 15 minutes, which continued to increase up to three hours. Ionomycin also induced hsp70 mRNA, which peaked at 30 minutes, and gradually decreased thereafter. The hsp70 induction following heat shock was attenuated when extracellular Ca2+ was reduced. Chelation of [Ca2+]i by quin-2 also reduced the hsp70 induction. Inhibitors of protein kinases, 1-(5-isoquinolinylsulfonyl)-2-methylpiperazine (H-7), calphostin C, genistein, and 2-aminopurine, also had inhibitory effects on the hsp70 induction. In contrast, a calmodulin inhibitor, chlorpromazine, had little effect. These results suggest that heat shock increases [Ca2+]i in rat PTE cells and that [Ca2+]i and protein kinases are involved in the hsp70 induction following heat shock. PMID- 8007581 TI - Altered cytosolic calcium homeostasis in rat cardiac myocytes in CRF. AB - Chronic renal failure (CRF) is associated with an increase in calcium content of heart. This was attributed to the secondary hyperparathyroidism of CRF, since PTH augments entry of calcium into cardiac myocytes. At present, it is not known whether the increase in calcium content of heart reflects a rise in basal levels of cytosolic calcium ([Ca2+]) of cardiac myocytes. Further, in order for the PTH induced entry of calcium into cardiac myocytes to raise their basal levels of [Ca2+]i, calcium extrusion out of these cells should be impaired as well. The present study examined the effect of CRF with and without excess PTH (PTX) and of the treatment of CRF rats with verapamil on basal levels of [Ca2+]i and ATP content of cardiac myocytes and on the activities of the pumps that are directly (Ca(2+)-ATPase and Na(+)-Ca2+ exchanger) and indirectly (Na(+)-K+ ATPase) responsible for calcium extrusion out of these cells. The basal levels of [Ca2+]i of cardiac myocytes increased (P < 0.01) and their ATP content decreased (P < 0.01) as the duration of CRF advanced. CRF was associated with significant decrement in Vmax of Ca2+ ATPase and Na(+)-K+ ATPase and in Na(+)-Ca2+ exchange. These derangements were prevented by prior PTX of the CRF rats or by their treatment with verapamil.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8007582 TI - Neutrophil activation in vitro and in vivo in Wegener's granulomatosis. AB - The mechanisms underlying glomerular capillary wall injury in Wegener's granulomatosis (WG) are not well understood. Anti-neutrophil cytoplasmic antibodies (ANCA), present in sera from patients with WG, are known to stimulate respiratory burst and degranulation of primed polymorphonuclear neutrophils (PMN) in vitro. Experimental studies have shown that oxygen radical production and lysosomal enzymes are important mediators of glomerular capillary wall injury. In the present study we investigated the presence of activated PMN and the extracellular localization of lysosomal enzymes in 28 consecutive renal biopsies from patients with WG. The presence of activated PMN within the renal biopsies was compared with the capacity of ANCA, isolated from simultaneously drawn serum samples, to activate primed PMN obtained from a normal donor. Both parameters were also related to renal function. Renal biopsies were obtained from newly diagnosed WG patients before therapy had started. Activation of PMN in the biopsies was assessed by measuring hydrogen peroxide production in situ. The number of activated PMN in the biopsy correlated with the extent of impairment of renal function. Proteinase 3, myeloperoxidase, and elastase, all targets of ANCA, were localized extracellularly in renal tissue and were also found within tubular epithelial cells. All ANCA positive samples were capable of activating primed PMN. The amount of activation correlated with the ANCA titer in those samples. No correlation, however, was found between the in vitro capacity of ANCA-positive IgG fractions to activate primed PMN and the number of activated PMN present in the renal biopsy. We conclude that activated PMN producing toxic oxygen metabolites and releasing lysosomal enzymes, are present in renal biopsies from patients with WG. The amount of activated PMN present within the kidney, and not the capacity of the corresponding ANCA to activate PMN, correlates with renal tissue damage as assessed by serum creatinine levels. PMID- 8007583 TI - Juxtaglomerular body abnormalities in youth-onset diabetic subjects. AB - Abnormal microalbuminuria in insulin-dependent diabetic subjects (IDDS) is significantly associated with pre-clinical nephropathy. In youth-onset IDDS declining plasma renin activity is significantly associated with improved albumin excretion, while persistently elevated renin activity is associated with continued abnormal microalbuminuria. To determine if these changes are reflected in changes in cell count in the juxtaglomerular body and if biopsy findings correlate with abnormal microalbuminuria, renal tissue of 20 IDDS (Study IDDS) ages 16 to 31 years, evaluated concurrently for plasma renin activity and microalbuminuria, were examined by light microscopy. Biopsy or autopsy specimens from 21 normal subjects and 32 IDDS (Non-Study IDDS), ages 2 to 25, were also examined. Specimens from the majority of prepubertal and all pubertal and postpubertal Non-Study IDDS and all Study IDDS independently of status of microalbuminuria had morphologic abnormalities. Normal or mesangially expanded glomeruli were found in association with expanded juxta-glomerular bodies and increased cell number, or with sclerotic bodies and decreased cell number. Sclerosis of juxtaglomerular bodies occurred independently of glomerular sclerosis. The highest percentage of glomeruli with expanded juxtaglomerular bodies and high cell count was present in specimens of Study IDDS with the most abnormal levels of microalbuminuria. T lymphocytes, noted within juxtaglomerular bodies, were present in specimens of 62% of the 52 Study and Non-Study IDDS. Abnormalities of the juxtaglomerular body are distinctive features of renal pathology in IDDS. T lymphocytes in the endocrine juxtaglomerular body suggest the presence of an autoimmune process. Confirmatory studies are necessary. PMID- 8007584 TI - Intracranial aneurysms in autosomal dominant polycystic kidney disease. AB - Rupture of intracranial aneurysm (ICA) is a rare but severe manifestation of autosomal dominant polycystic kidney disease (ADPKD). In order to assess its natural history, to determine the prevalence of familial aggregation and to document linkage to PKD1 locus, we conducted a retrospective study on 77 ADPKD patients from 64 families presenting with ruptured (N = 71) or unruptured (N = 6) aneurysm. Information was collected on kidney disease, intracranial aneurysm and family history. Linkage to PKD1 locus was examined by five probes to obtain informative flanking markers. Within one year prior to rupture, blood pressure was normal in 29% of the patients. At the time of rupture, mean age was 39.5 years (range 15 to 69), renal function was normal in half of the patients and 11% were on renal replacement therapy. The ruptured aneurysm was usually located on the middle cerebral artery. Additional intact aneurysms (1 to 6) were detected in 31% of the patients. Surgical or endovascular treatment was performed in 54 (76%) patients whereas 17 (24%) had medical management only. Rupture of ICA was fatal in seven (10%) patients. On long-term follow-up 27 (38%) were left with severe disablement. Five patients bled from another aneurysm 2 days to 14 years after initial rupture. Only two of six patients with unruptured aneurysm alone were treated on a prophylactic basis. No clinical marker associated with aneurysm was found. A family history of aneurysm rupture was demonstrated in 10 (18%) kindreds. Linkage to the PKD1 locus was established in two of three tested families.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8007585 TI - Glucose oxidation after a peritoneal and an oral glucose load in dialyzed patients. AB - Glucose oxidation and thermogenesis were studied after a peritoneal (P) and an oral (O) glucose load in nine chronically uremic patients undergoing continuous ambulatory peritoneal dialysis (CAPD) for 24.4 +/- 5.8 months. The O load (50 g) given was equivalent to the amount of glucose absorbed over six hours through the peritoneum of the subjects (51.7 +/- 3.3 g). Glucose oxidation and energy expenditure were obtained using indirect calorimetry in basal state and over the six hours following the glucose load. Glucose oxidation rate was higher from 60 to 180 minutes after O than after P (P < 0.05), with peak values of 3.85 +/- 0.28 mg.kg-1.min-1 and 2.80 +/- 0.17 mg.kg-1.min-1 respectively (P < 0.05). Cumulated glucose oxidation over six hours was 53.6 +/- 0.6 versus 47.0 +/- 3.4 g after O and P respectively (NS). Glucose-induced thermogenesis was 8.7 +/- 2.9% versus 5 +/- 1.9% after O and P, respectively (NS). The route of administration of glucose induces different kinetics of the glucose oxidation rate, but a similar amount of glucose absorbed either by the peritoneum or by the gut contributes in a similar extent to glucose and energy balance. PMID- 8007586 TI - Is there evidence for anticipation in autosomal-dominant polycystic kidney disease? AB - The heritability of autosomal-dominant polycystic kidney disease (ADPKD) is marked by an apparent high mutation rate, neonatal onset of disease in some patients and intrafamily variability. These findings raise the possibility of genetic anticipation in ADPKD as has been observed in fragile-X syndrome, myotonic dystrophy and Huntington's disease. We reviewed 242 pedigrees obtained during our prospective studies on the natural history of ADPKD. Anticipation was defined as a 10 year earlier onset of ESRD in offspring as compared to their affected parent or a child diagnosed in the first year of life. Due to the slowly progressive nature of ADPKD, 148 pedigrees were uninformative. Anticipation of ESRD was found in 49% of informative families in at least one parent-offspring pair, and when early onset children were included, 53% of informative families had at least one parent-offspring pair with anticipation. Moreover, the transmitting parent in the pairs with anticipation was more often the mother than the father, similar to myotonic dystrophy, where the most dramatic form of anticipation, congenital disease, occurs almost exclusively with maternal transmission. These observations suggest that ADPKD may be another genetic disorder characterized by heritable unstable DNA. PMID- 8007587 TI - Continuous ambulatory peritoneal dialysis and hemodialysis: comparison of patient mortality with adjustment for comorbid conditions. AB - A historical prospective national sample of 1,725 diabetic and 2,411 non-diabetic Medicare end-stage renal disease (ESRD) patients incident from 1986 to 1987 was analyzed for the mortality of patients selected to receive continuous ambulatory peritoneal dialysis (CAPD) or hemodialysis (HD) with adjustment for patient characteristics, including the presence of comorbid conditions at onset of ESRD. Cox proportional hazards analyses were used to compare the mortality of CAPD and HD patients. Patients were followed from 30 days following onset of ESRD until two to four years post-onset. No statistically significant difference in relative mortality risk (RR) was found among non-diabetic patients selected for CAPD compared to HD (RR = 0.84 for CAPD versus HD, P = 0.25), while evidence of higher adjusted mortality for CAPD compared to HD was found among diabetic patients (RR = 1.26, P = 0.03). Mortality analyses adjusted for pre-treatment risk factors suggest that CAPD and HD provide incident non-diabetic ESRD patients with similar expected survival outcomes. Evidence that increased mortality was associated with CAPD among diabetic patients, particularly among elderly patients, suggests the need for further controlled studies of mortality among CAPD patients with diabetes. PMID- 8007588 TI - Aspirin renography to detect unilateral renovascular hypertension. PMID- 8007589 TI - Correction of central venous stenoses: use of angioplasty and vascular Wallstents. AB - Central venous stenoses are a frequent complication in hemodialysis patients. These lesions lead to fistula thromboses, arm swelling, and limit future vascular access. Stenoses are characterized by excellent initial response to transluminal angioplasty but rapid recurrence. Response to angioplasty allows classification of stenoses as elastic or nonelastic. The success of angioplasty alone in 30 patients with central venous stenoses was compared to angioplasty and Wallstent placement in 11 patients with recurrent stenoses. In those who had angioplasty alone, 7%+ failed angioplasty, 70% had > or = 50% improvement in the luminal diameter while 23% showed no improvement due to elastic lesions. Subsequently, 81% of those with a successful result restenosed at an average of 7.6 months while 100% of elastic lesions occluded in an average of 2.9 months. In the 10 patients who underwent angioplasty and Wallstent placement, 5 were due to elastic lesions with four recurrences at a mean of 8.6 months. Four of five patients (80%) stented with nonelastic lesions had reappearance of symptoms at a mean of 4.2 months. We conclude that vascular stents should be reserved for those lesions that show elastic recoil after standard angioplasty. PMID- 8007591 TI - Therapy for idiopathic membranous nephropathy: tailoring the choice by decision analysis. AB - Two Italian controlled trials demonstrated that the difference in remission rates obtained with six months of methylprednisolone and chlorambucil (MP+Ch) compared to MP was smaller than MP+Ch versus symptomatic therapy in the treatment of idiopathic membranous nephropathy nephrotic syndrome (NS). A decision analysis was used to compare the three treatment strategies, assuming triple probabilities and costs for MP+Ch complications compared to MP, with no risk for supportive therapy, referring to an average 40-year-old patient and using the quality adjusted life expectancy year (QALY) as the utility scale. With MP+Ch the difference in expected QALY was 7.2 years compared to supportive therapy, and 2.6 years compared to MP. To offset the longer survival obtained with MP+Ch versus MP, it was assumed that all patients treated with MP+Ch would undergo either fatal (5% vs. 0.3% with MP) or non-fatal complications (95% vs. 15% with MP). This threshold denotes a great stability of the inequality in the expected QALY. Consequently, treatment with MP or with MP+Ch is justified if their side effects are considered to be a suitable trade-off for a five or seven QALY, respectively, longer survival. Only an absurd increase in the death rate with MP+Ch could offset the difference. PMID- 8007590 TI - Adaptive responses to very low protein diets: the first comparison of ketoacids to essential amino acids. AB - Eight patients with chronic renal failure (GFR 18.8 +/- 2.7 ml/min) were randomized to a crossover comparison of a very low protein diet (VLPD) containing 0.28 g protein and 35 kcal per kg per day, plus an isosmolar mixture of either ketoacids (KA) or essential amino acids (EAA). Subjects initiated the diets 14 days before hospital admission and following a four-day equilibration, a five-day nitrogen balance (BN) was performed. Whole-body protein turnover (WBPT) was measured during fasting and feeding using intravenous [1-13C]leucine and intragastric [5,5,5-2H3]leucine. Even though the VLPD/KA regimen contained 15% less nitrogen, BN was neutral and did not differ between the regimens. Nitrogen conservation with KA was due to a reduction in urea nitrogen appearance. Rates of WBPT measured during fasting and feeding did not differ between the KA or EAA regimens. During both regimens, feeding decreased protein degradation, whereas protein synthesis was unchanged. Although feeding stimulated leucine oxidation, rates were 50 to 100% lower than reported in CRF patients consuming 0.6 or 1.0 g protein/kg/day. Thus, neutral Bn with the VLPD regimen is achieved by a marked reduction in amino acid oxidation and a postprandial inhibition of protein degradation. PMID- 8007593 TI - Reliable atomic absorption analysis of sodium and potassium in rat renal tubular fluid. PMID- 8007592 TI - Sequential effects of cyclosporine therapy on blood pressure, renal function and neurohormones. AB - We have studied the sequential effects of cyclosporine during the first four days after its initiation in an effort to elucidate the primary and secondary events in the pathogenesis of cyclosporine induced nephrotoxicity and hypertension. Knowledge about the earliest effects of cyclosporine provides a more logical approach for devising therapeutic strategies to counteract nephrotoxicity and hypertension. On day 1, cyclosporine acutely increased systemic BP and decreased urine volume. Plasma renin activity was suppressed by day 2 and remained so thereafter. Renal sodium excretion was not affected until day 4 at which point a natriuresis occurred. Cyclosporine exerted a more marked antidiuretic effect on day 4 compared to day 1, which was augmented by a physiological infusion of vasopressin. Over the first four days of therapy, glomerular filtration rate and effective renal plasma flow were unchanged. Our data show that cyclosporine induced hypertension in the initial stages is not sodium dependent, and that changes in renal water handling were not dependent on alterations in the glomerular filtration rate or effective renal plasma flow. In fact, a natriuresis occurred which was most likely due to a combination of pressure natriuresis and angiotensin II suppression. The cyclosporine induced antidiuresis may indicate a distal nephron effect since cyclosporine augmented the antidiuretic effect of vasopressin, although vasopressin levels per se were not increased by cyclosporine alone. PMID- 8007594 TI - Adenoviral-mediated gene transfer to renal tubular cells in vivo. AB - The efficient introduction of genetic material into quiescent renal cells is potentially important in the study of renal physiopathology and for gene therapy of kidney related disorders. A replication-deficient adenoviral vector that contained a reporter gene encoding the nuclear beta-galactosidase was either selectively perfused into the renal artery or infused through a retrograde catheter into the pyelic cavity of the left kidney of adult rats. Highly efficient gene transfer was achieved by either route of administration, and nuclear beta-galactosidase activity was detected for two to four weeks following a progressive decline of expression. Genetically-modified cells were identified as proximal tubular cells when the adenoviral vector was selectively perfused via the renal artery, while tubular cells from the papilla and medulla were selectively transduced by retrograde infusion of the viral vector. No obvious cytopathic effect was observed. We conclude that: (i) efficient gene transfer in renal tubular cells can be achieved by adenoviral vectors; (ii) the targeted cell population can be chosen through the route of administration. PMID- 8007595 TI - Peritoneal dialysis. PMID- 8007596 TI - Osmotic diuresis before Homer W. Smith: a winding path to renal physiology. AB - It was towards the end of the 18th century that a curiosity arose about what controlled the flow of urine. It was noted that though a patient's kidneys might be destroyed, the flow of urine continued until death. This puzzling phenomenon might have been understood had Segalas's and Wohler's observations been properly appreciated, that an extra load of urea, or any other substance that is excreted by the kidney, causes a diuresis. Nevertheless, these experiments were forgotten, and because of Bowman's and Ludwig's studies fluctuations in urine flow were ascribed to changes in blood pressure. It was not until 1870 to 1880 that Ustimowitsch, Falck and Richet stressed the role of urinary solutes on urine flow. Around 1900, Cushny also studied the diuretic effect of different solutes excreted in the urine and actually described what is now called an osmotic diuresis, though he did not use the term. These studies enabled him to deliver his "modern view" of the Secretion of the Urine. This was the first coherent concept which attempted to explain the formation of the urine and the regulation of its composition according to a pressure of a selective tubular reabsorption controlled by the needs of the "Milieu Interieur." When glomerular and tubular functions became quantifiable, Homer W. Smith's disciples were able to define the exact nature of an osmotic diuresis and that explained the paradox of polyuria and renal failure. PMID- 8007597 TI - Macrophages in acute glomerular inflammation. PMID- 8007598 TI - Factors in the development of secondary hyperparathyroidism during graded renal failure in the rat. AB - Secondary hyperparathyroidism (2 degree HPT) develops as a result of renal failure. Hypocalcemia, phosphorus retention, calcitriol deficiency and skeletal resistance to the calcemic action of parathyroid hormone (PTH) are closely interrelated pathogenic factors important for the development of 2 degrees HPT in renal failure. Since previous studies have mainly focused on advanced renal failure, only limited data are available in early renal failure. The goal of the present study was to evaluate how alterations in the dietary calcium and phosphorus composition affect the factors known to contribute to the genesis of 2 degrees HPT in early and more advanced renal failure. To achieve this goal, graded differences in renal function were surgically induced in 453 rats while the dietary content of calcium and phosphorus was varied. Three different diets were used: (1) a high phosphorus diet (HPD), to induce phosphorus retention and stimulate 2 degrees HPT; (2) a high calcium diet (HCaD), to inhibit calcitriol synthesis; and (3) a moderate calcium-moderate phosphorus diet (MCaPD), to separate the effects of high dietary phosphorus and calcium. Based on the serum creatinine (SCr) concentration rats were assigned to one of four different groups: (1) normal renal function (SCr < or = 0.3 mg/dl); (2) mild renal failure (SCr 0.4 to 0.6 mg/dl); (3) moderate renal failure (SCr 0.7 to 0.8 mg/dl); or (4) advanced renal failure (SCr > or = 0.9 mg/dl). As the severity of renal failure increased, progressive 2 degrees HPT developed in each of the dietary groups.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8007600 TI - 15-HETE: selective incorporation into inositol phospholipids of MDCK cells. AB - The interaction of 15-hydroxyeicosatetraenoic acid (15-HETE) and cultured MDCK renal tubular epithelial cells was investigated to determine whether incorporation of this lipoxygenase product will affect polyphosphoinositide formation. MDCK cells were incubated with 1 microM [3H]-15-HETE for 15 to 120 minutes. Maximum uptake occurred between 15 and 30 minutes, and after 60 minutes, 70% of the incorporated 15-HETE was present in the phosphatidylinositol (PI) fraction. Some 15-HETE was also incorporated into phosphatidylinositol-4 monophosphate (PIP) and phosphatidylinositol-4,5-bisphosphate (PIP2). However, even though more 15-HETE than arachidonic acid was incorporated into PI, the fractional amount of 15-HETE present in the polyphosphoinositides was smaller than arachidonic acid. Therefore, although 15-HETE is selectively channeled into PI, conversion of PI species containing 15-HETE to PIP and PIP2 is relatively impaired. This suggests that either PI containing 15-HETE is a less effective substrate for phosphorylation, or PI containing arachidonic acid is a preferred substrate. MDCK cells converted 15-HETE to polar metabolites that were released into the extracellular fluid. This process may constitute a renal tubular mechanism for the clearance of 15-HETE and related lipoxygenase products. PMID- 8007599 TI - Glomerulopathy induced by IgG3 anti-trinitrophenyl monoclonal cryoglobulins derived from non-autoimmune mice. AB - We have previously shown that murine IgG3 monoclonal autoantibodies with cryoglobulin activity, derived from lupus-prone mice, are able to induce glomerular lesions resembling the "wire-loop" lesion typically described for human lupus nephritis. In the present study, we have further assessed the nephritogenic potential of four IgG3 anti-hapten, trinitrophenyl (TNP), monoclonal antibodies (mAb) obtained from non-autoimmune mice immunized with TNP conjugated foreign antigens. Our results showed that two of four IgG3 anti-TNP monoclonal cryoglobulins were capable of inducing glomerular lesions, characterized by voluminous intracapillary thrombi and mesangial deposition of PAS-positive materials, which differed from "wire-loop" lesions generated by IgG3 monoclonal cryoglobulins with autoantibody activities. These anti-TNP monoclonal cryoglobulins, however, failed to induce glomerular lesions when mice were kept at 37 degrees C after the mAb administration. This finding formally proves that the cryoglobulin activity is critically involved in the development of glomerular lesions induced by IgG3 anti-TNP mAb. In addition, we have demonstrated a remarkable difference in the nephritogenic activities of two IgG3 anti-TNP mAb, which exhibit a marked sequence homology in the variable regions of their heavy and light chains (91.5% and 99.1% at the amino acid level, respectively) and an identical isoelectric point. Our results indicate first, that IgG3 monoclonal cryoglobulins are able to generate two different kinds of glomerular lesions, and second, that a subtle difference in variable region sequences may determine not only the nephritogenic activities, but also the type of glomerular lesions mediated by IgG3 cryoglobulins. PMID- 8007601 TI - Loop diuretics reduce hypoxic damage to proximal tubules of the isolated perfused rat kidney. AB - The straight portion (S3) of the proximal tubule lies in close proximity to the thick ascending limbs (TALs) at the cortico-medullary junction. Since a delicate balance exists between oxygen demand and the limited oxygen supply in this region, we hypothesized that reduction of thick limb metabolic activity might augment oxygen availability to S3 segments, which depend heavily upon aerobic metabolism, and prevent hypoxic damage. The degree of functional deterioration and morphological damage to S3 was assessed in isolated rat kidneys perfused with an erythrocyte-free medium. Bumetanide (10(-5) M) and furosemide (10(-4) M) reduced S3 fragmentation from 9.8 +/- 3.9% of tubules in controls to 0 and 1.4 +/ 0.9%, respectively (P < 0.0005). Tubular glucose reabsorption was better preserved in kidneys exposed to loop diuretics than in control kidneys (P < 0.01), and urinary alkaline phosphatase (P < 0.05) and the total amount of LDH released into the perfusate and urine (P < 0.01) were lower in the treatment groups. Morphological damage to S3 was closely correlated with medullary TAL necrosis (r = 0.66, P < 0.001), urinary alkaline phosphatase excretion (r = 0.89, P < 0.001) and glycosuria (r = 0.83, P < 0.001). We conclude that under hypoxic conditions TALs and S3 segments may compete with each other for a limited oxygen supply. Reduction of active transport in the mTAL might augment oxygen availability to S3 segments and improve their survival. PMID- 8007603 TI - Histone mediates glomerular deposition of small size DNA anti-DNA complex. AB - Histone can mediate the binding of free DNA to the glomerular capillary wall. We tested whether histone could mediate the deposition of preformed DNA-anti-DNA immune complex (IC). IC were generated using monoclonal anti-DNA Ab and excess of small size 125I-DNA; after further digestion with DNase the IC, containing 5 micrograms DNA (now 20 to 60 bp), was injected into the left kidney of rats. When given alone, only about 0.2% of the IC bound in glomeruli. Prior injection of 200 micrograms of core histones (H2A,H2B,H3,H4) resulted in high glomerular binding of the IC; 18.1% of the injected dose (measured as 125I-DNA) was bound at 15 minutes. Mouse immunoglobulin, representing the IC, could be seen in a capillary pattern. C3 was also present in a similar pattern, showing that complement had been activated. Discrete electron-dense deposits were seen in a subendothelial and subepithelial localization at 15 minutes. Although about 1 microgram of DNA was deposited in the glomeruli, it could not be detected by indirect immunofluorescence or intercalating dyes. These studies provide direct evidence that histones can mediate the binding of particular circulating DNA-anti-DNA immune complexes to the glomerular capillary wall in vivo. If small size DNA fragments (< 100 bp) are involved in lupus nephritis, our results provide a possible explanation for the frequent failure to detect DNA deposits in renal biopsies from SLE patients. PMID- 8007602 TI - Exclusion of eight genes as mutated loci in congenital nephrotic syndrome of the Finnish type. AB - The congenital nephrotic syndrome of the Finnish type (CNF) is an autosomal recessive disease characterized by massive proteinuria already at birth. The gene locus defective in CNF was searched for using polymorphic markers of candidate genes coding for components of the basement membrane (BM). The linkage analyses in 17 Finnish CNF families demonstrated exclusion of obligatory recombination events between the disease and eight genes coding for BM components. The genes coding for the alpha 1(IV), alpha 2(IV), alpha 3(IV) and alpha 4(IV) chain of type IV collagen, the B1e, B2e and B2t chains of laminin, as well as the BM heparan sulfate proteoglycan core protein were all excluded in this Finnish family material. Since the defect is not in any of the genes coding for major components of BM, the identification of the gene defect will most probably reveal a new gene important for the development and function of the glomerular basement membrane. PMID- 8007604 TI - [Invaginational antireflux esophageal anastomosis in gastrectomy and proximal resection of the stomach]. AB - Incompetence of esophageal anastomoses and reflux esophagitis are frequent complications occurring after gastrectomy and proximal resection of the stomach. The authors examined 149 persons who underwent operations for carcinoma of the stomach and lower third of the esophagus. In a group of 47 patients who underwent gastrectomy or proximal resection of the stomach with the formation of the ordinary not areflux anastomoses, nine died from incompetence of the sutures. In study of the late-term results gastroduodenoscopy revealed reflux esophagitis in 22 persons. Intraesophageal pH measurement showed values of 2.0 to 3.0. In 20 patients of this group piezo-resonance manometry demonstrated an essential unfavorable feature of the intraluminal pressure gradient--the intraluminal pressure was lower in the esophagus than in the stomach stump anastomosed with it or in the loop of the small intestine. This facilitated the development of reflux esophagitis. The authors developed a method of invagination areflux esophageal anastomosis by the closed techniques with the use of laser. The anastomosis is formed by two continuous sutures of a synthetic absorbable thread with an autraumatic needle. Incompetence of the sutures occurred in two patients. Piezoresonance manometry revealed a zone of increased intraluminal pressure in the region of the esophageal anastomosis. Mild reflux esophagitis was encountered in three patients. The authors recommend a new modification of esophageal anastomosis for surgical practice. PMID- 8007605 TI - [Laparoscopy in the differential diagnosis of acute abdomen]. AB - The work analyses the results of emergency laparoscopy in 4,730 patients with acute surgical pathology of the abdominal organs. There were 26.3% of males and 73.7% of females; 26.5% of patients were of an elderly age. Laparoscopy was undertaken in all cases in which the diagnosis was questionable but the clinical picture was that of "acute abdomen" and in patients with an established diagnosis for conducting therapeutic manipulations: microcholecystostomy, drainage of the abdominal cavity. The authors show differential endoscopic signs of some acute surgical diseases of the abdominal organs. Laparoscopy confirmed the clinical diagnosis in 45.5% of cases and revealed indications for an emergency operation in 896 patients (33.8%). Laparoscopic microcholecystostomy was performed 137 times and drainage of the abdominal cavity 398 times. The diagnostic value of laparoscopy came to 97.1% on the average. PMID- 8007607 TI - [Intensity of lipid peroxidation in the small intestinal wall in peritonitis and its correction]. AB - Experiments were conducted on albino rats to study lipid peroxidation (LPO) in muscle homogenates of the small intestine in peritonitis of various duration. LPO increased most significantly in 24-hour peritonitis. There was no statistically significant difference between the LPO values two days later and those of 24-hour peritonitis. With the use of the antioxidant alpha-tocopherol with essential 12 hours after the development of peritonitis no significant changes occurred in the LPO values. In 24-hour peritonitis LPO was initiated but it was less pronounced. alpha-Tocopherol acetate and essential were included in the complex of therapeutic measures in 20 patients. They were administered before and 3-4 days after the operation. As a result the motor-evacuation function of the gastrointestinal tract was restored in a shorter time. The postoperative period took a favorable course, and the duration of in-hospital treatment reduced by 2-3 days on the average. PMID- 8007606 TI - [Combined detoxification and immunocorrective therapy in patients with peritonitis]. AB - The authors examined 48 patients with peritonitis (20 with the generalized and 28 with the localized form). The content of T-lymphocytes, theophylline-resistant and theophylline-sensitive T-lymphocytes, leukocyte chemotaxic activity, and the lymphocyte ATP content were studied. It was found that the state of the immune system in the early postoperative period allows the severity of the disease and its outcome to be prognosticated. A sharp decrease in the T-lymphocyte content and decrease of the amount of ATP in the lymphocytes in stable reduction of chemotaxic activity is an unfavorable prognostic sign. Introduction of indirect electrochemical oxidation with a sodium hypochlorite solution into the complex of intensive therapy produces, in addition to a marked detoxification effect, a stabilizing effect on metabolic processes in the lymphocytes and activates the cellular link of immunity. Combined immunocorrection with the agents tactivin and leukinferon possesses a high potential of an immunobiological effect and can be recommended for correction of severe secondary immunodeficiency in patients with generalized peritonitis. PMID- 8007608 TI - [Results of surgical treatment of diastasis of the rectus abdominis muscles]. AB - The work gives a comparative analysis of the treatment of 249 patients with diastasis of the rectus abdominis muscles according to the degree of restoration of the working capacity, the existence of gastrointestinal discomfort, recurrence of the disease, and the dynamics of changes of the morphological and functional values of these muscles. The clinical and functional-morphological results were best after plastics of the anterior abdominal wall by the method suggested by the authors. With the use of this method the results were good in 40 (71.4%) and satisfactory in 16 (28.6%) of patients. Recurrences were not encountered. PMID- 8007610 TI - [Secondary surgical debridement in the treatment of infectious purulent complications of gunshot wounds]. AB - Perfection of firearms led to injuries of a more severe character and, consequently, to increased frequency of wound infections and to their poorer clinical course. In view of which the role of secondary surgical debridement for the removal of the suppuration substrate increases as the most effective method for the treatment of infection-purulent complications of gunshot wounds. However, to gain good results in this case the principles of surgical debridement of gunshot wounds must be strictly followed. Only with adequately accomplished secondary surgical debridement will the other additional surgical and therapeutic measures produce a good effect on the purulent wound and on the organism of the injured person. PMID- 8007609 TI - [Use of UV-irradiated donor plasma in the treatment of destructive pancreatitis]. AB - Donor plasma exposed to UV rays was included in the complex of measures for the treatment of diffuse pancreonecrosis with marked signs of enzyme toxemia and endogenous intoxication in 14 patients. The irradiation was conducted on an original device in which a [symbol: see text] lamp with a wave length of 253.6 nm was used as the source of radiation. Study of the dynamics of changes in the level of lipid peroxidation, alpha-tocopherol, trypsin, and lipase allows the conclusion that infusion of donor plasma exposed to UV radiation has a favorable effect on processes of detoxification of the organism. PMID- 8007611 TI - [Acute pancreatitis and biological antioxidants]. AB - The values of lipid free--radical oxidation and the effect of various methods of treatment on these processes were studied in 164 patients with acute pancreatitis. Combined use of oil emulsions with agents possessing antioxidation activity (unithiol, tocopherol) produced the best values. Combined therapy promoted normalization of the main parameters characterizing the activity of lipid peroxidation reactions which was attended with reduced concentrations of pancreatic enzymes and increased concentration of beta-lipoproteins in the blood. This was indicative of stabilization of the pancreatic cell membrane systems. PMID- 8007612 TI - [Controlled digital closure in liver resection]. AB - The work generalizes the experience in the treatment of patients with local diseases of the liver at the hospitals of the Samara Region in 1971-1988. During this period 101 anatomical resections of the liver in 100 patients were performed. The operations were conducted by two technical procedures: the traditional method and the method of controlled digitoclasia. Twenty-six patients were operated on by the traditional methods, who had a 16% mortality rate. The method of controlled digitoclasia was applied in 74 patients with 5.2% mortality. The article describes the suggested method of anatomical resection of the liver in detail and evaluates its clinical approbation with that of the traditional methods. PMID- 8007613 TI - [Diagnosis and treatment of liver abscesses]. AB - The results of the diagnosis, the clinical picture, and the treatment of hepatic abscesses in 68 patients are analysed. Ultrasonic examination plays an essential role in the diagnosis of the disease. Percutaneous transhepatic puncture with aspiration of the contents of the hepatic abscess was conducted in 17 patients under control of ultrasonic study. Sixteen of these patients recovered without a surgical intervention. A laser scalpel was used in 39 patients with quite encouraging results. It is concluded that puncture drainage of hepatic abscesses and operations with the use of the laser techniques are promising methods. PMID- 8007614 TI - [A choice of reconstructive plastic surgery with endoprosthesis of the breast after radical mastectomy]. AB - The creation of silicone endoprosthesis led to new approaches in solving the problems of plastic replacement of the breast after radical mastectomy. Two variants of reconstructive plastic operations with endoprosthetics of the breast were employed: group one--the formation of the seat of the endoprosthesis using a transposed musculocutaneous flap from the latissimus dorsi muscle; group two--the formation of the seat of the endoprosthesis by stretching the skin with a specially designed stretcher-expander and subsequent implantation of the endoprosthesis. The first method is rather injurious, sometimes cannot be performed because of anatomical contraindications, and is fraught with the development of necroses in the transposed tissues. Among 34 patients operated on by the first method two had marginal necrosis of the skin above the endoprosthesis. No complications were recorded among the 46 patients who underwent operation by the second method. The condition of the endoprosthesis and the tissues surrounding it was appraised in the immediate and late periods by radiological and ultrasonic examination. The variants of endoprosthetics of the breast which we applied may be employed with competence in clinical practice, but a reconstructive-plastic operation with the use of a skin expander is preferable. PMID- 8007615 TI - [Bleeding as a cause of mortality in thoracic surgery]. AB - Analysis of hospital lethality showed that hemorrhage was the cause of lethal outcomes in thoracic surgery among 0.5% of all hospitalized patients, 0.8% of those who underwent operation, and 17.3% of all patients who died. Among all fatal hemorrhages 28.6% were surgical and 71.4% were erosional. Surgical hemorrhage was due to injury inflicted to the large vessels (atria) during the operation. Erosional hemorrhages were caused by postoperative infectious-septic complications, progressive malignant tumors and pyo-purulent diseases, and exacerbation of peptic ulcer or the formation of an acute gastric ulcer. Among the principal causes of fatal hemorrhages are defective treatment (32.9% of cases), methodical and technical errors during the operation (28.6%), erroneous diagnosis (25.3%), initially severe condition of patients (6.6%), and progressive malignant tumor (6.6%). Intraoperative prevention of fatal surgical hemorrhage is based on personal experience, knowledge and skill of surgeons, and the use of modern technology in the control of blood loss. The prevention of erosional hemorrhage in patients who are not operated on consists in timely surgical treatment and early diagnosis in the postoperative period and active treatment of infectious-septic complications. PMID- 8007616 TI - [Formation of subfascial lymphovenous anastomoses on the foot]. AB - The author suggests a new modification of operation for formation of subfascial lymphovenous anastomoses (LVA) on the dorsum of the foot in treatment of edema of the lower limbs. Sixty-two patients underwent operation. In 34 patients of the control group an epifascial LVA was formed on the dorsal surface of the foot. The operation for LVA anastomosis was combined with fenestration of the leg fascia. A positive effect of various degree was produced in the postthrombotic syndrome in 84% of the studied patients (in 29% of the controls) and in 94% of cases of II degree lymphedema (in 56% of the controls). The expediency of subfascial LVA is substantiated clinically and physiologically. PMID- 8007617 TI - [Some aspects of venous surgery based on advanced knowledge of venous anatomy of the lower extremities]. AB - Analysis of the errors and faults in the treatment of the main diseases of veins of the vena cava inferior system showed that they can be explained to a great extent by the uncoordinated ideas of the anatomy of the lower limb venous channel. Our experience suggested the expediency of evaluating the condition of venous circulation from the standpoint of comprehensive consideration of the vascular channel structure. The suggested scheme of the structure of the venous channel with all the collaterals and the intravenous connections is systematized and logically completed. We employed it for analysis of some up-to-date problems of the diagnosis and treatment of the most frequently encountered diseases of the lower limb venous system. Knowledge of the general and individual characteristics of the structure of the venous channel opens up new opportunities for their use in surgery and at the same time protect against unreasoned and erroneous decisions. PMID- 8007620 TI - [Hepatic lymphangioma]. PMID- 8007619 TI - [Surgical treatment of acute destructive pancreatitis]. AB - The possibilities of the accepted surgical tactics in the treatment of acute destructive pancreatitis based on a single operative intervention with drainage of the omental bursa and retroperitoneal space are very limited. It is not always possible to remove the necrotic tissues fully, arrest the inflammatory process, and completely cleanse the abdominal cavity, omental bursa, and parapancreatic fat during the operation. Reasoning from this, the authors suggest a method for treating acute destructive pancreatitis. It consists in the creation of an omentobursopancreatostoma followed by stage endoscopic necrectomy of pancreatic areas and endoscopic control over the course of regeneration in the omental bursa and retroperitoneal space till a chronic pancreatic fistula forms, which usually spontaneously closes later. With the use of this method in 46 patients with pancreonecrosis, postoperative complications and mortality reduced. PMID- 8007618 TI - [Treatment of epitheliomas]. AB - In a period of 6 years the authors had 615 patients with epitheliomas. Squamous cell carcinoma (SCC) was found in 22 of them, meta-typical carcinoma in 2, and basal cell carcinoma (BCC) in the remaining cases. The frequency of application and comparative efficacy of various methods of treatment were appraised. The surgical method was used most frequently--in 84.2% of patients. Cryodestruction prevailed (46.3%) among the surgical methods of epithelioma treatment. Its early results in BCC were favorable in 97% of cases. The frequency of recurrences and metastases was 0.5%. Surgical excision, applied in 31% of patients, was effective in all cases of BCC. In SCC surgical excision is performed in a complex with radiotherapy. The efficacy of combined treatment (surgery + radiotherapy) was about 100%. Generalization of the process was found in only one patient. The other methods of treatment are used much less frequently. PMID- 8007621 TI - [Surgical treatment of hemorrhaging stomach ulcer in acute renal insufficiency]. PMID- 8007622 TI - [Strangulated inguinal hernia with strangulation of Meckel's diverticulum]. PMID- 8007623 TI - [Perforated pyloric and prepyloric ulcers]. AB - Various surgical interventions were conducted in the clinic on 63 patients for perforation of pyloric and prepyloric ulcers. Closure of the perforated ulcer was performed in 8 patients, excision of the ulcer and transverse pyloroplasty in 14, truncal and selective vagotomy in combination with antrumectomy in 6, and truncal vagotomy and pyloroplasty in 3 patients. According to the authors, the operation of choice is anterior seromyotomy of the body and fundus of the stomach in combination with posterior truncal or posterior selective vagotomy and obligatory excision of the ulcer for histological study, and transverse pyloroplasty of the Aust-Holle type which was performed in 22 patients. The indications for radical operations were expanded bearing in mind the peculiarities of the course of peritonitis in patients with perforated gastric ulcers. In addition to the traditional prophylactic treatment of the abdominal cavity, the complex treatment of peritonitis included the use of low-frequency ultrasound during the operation and prolonged laparoscopic prophylactic treatment with low-intensity laser beam in the postoperative period. PMID- 8007624 TI - Two novel genes of herpes simplex virus type 1 involved in cell fusion. AB - Herpes simplex virus type 1 (HSV-1) r mutants, which were defective in fusion function, were isolated from fusion inducing strains G7471 and G51, and classified into several groups by complementation (Yamamoto and Kabuta, 1977; Yamamoto et al. 1989). Marker rescue experiments of intact DNA from r mutants with EcoRI fragments of G7471 DNA revealed that the r mutations belonging to the groups A, B, E, F, G, and H were located in EcoRI-g, -c, -d, -h, -b, and -d fragments, respectively. The mutations belonging to the groups A, B, F, and G cover the loci affecting cell fusion which have been already reported by other investigators. The two novel mutations localized in EcoRI-d fragment were further finely mapped, and it was demonstrated that the mutations belonging to groups E and H were involved in the open reading frames UL10 and UL13, respectively. PMID- 8007625 TI - Heterogeneity of the afterhyperpolarization of sympathetic preganglionic neurons. AB - The components of the afterhyperpolarization (AHP) of the sympathetic preganglionic neuron were studied in the slice of the upper thoracic spinal cord of the cat. In this neuron, the AHP consists of a fast (fAHP) followed by a slow (sAHP) component. While the fAHP had similar time course in all neurons studied (n = 116), the sAHP had considerable variability. Two components could be identified and the variability resulted from variation in the relative magnitude of these. Fifteen percent of neurons showed only an early component of the sAHP, 16% showed only a late component, and 69% showed both components. The early component of the sAHP was selectively blocked by apamin and d-tubocurarine, while the late component was selectively blocked by ryanodine, procaine or phenylephrine. PMID- 8007626 TI - Clinicopathologic parameters in predicting cervical nodal metastasis in early squamous cell carcinoma of the oral cavity. AB - A retrospective study of ninety patients with early squamous cell carcinoma of the oral cavity was undertaken to evaluate clinical and histopathologic parameters in predicting cervical lymph node metastasis. Medical records were examined for age, sex, primary site, growth pattern, and size. The specimens from biopsy and surgical excision were examined for the degree of differentiation, mode of invasion, tumor thickness, muscular invasion, vascular invasion, and inflammatory response. The mode of invasion and tumor thickness were important indicators in the prediction of cervical lymph node metastasis. Tumors with Grade 4 mode of invasion exceeding 3 mm in thickness or with Grade 3 and 4 modes of invasion and more than 6 mm in thickness had a high incidence of cervical nodal metastasis. These important prognostic variables were best evaluated in the deeper portions of the lesions. PMID- 8007627 TI - Transfusion-associated graft versus host disease following hepatectomy for hepatocellular carcinoma--a case report. AB - A case of transfusion-associated graft versus host disease (TA-GVHD) following hepatectomy for hepatocellular carcinoma is described in a 53 year-old male patient. The intraoperative bleeding was estimated to be 1220 ml, and he was transfused with 4 units of fresh whole blood. On postoperative day (POD) 12, a fever of 38 degrees C developed, followed by a systemic erythema on POD 14, and a marked progressive leukopenia starting from POD 19. The patient died of multiple organ failure (MOF) on POD 29. Just before death, the results of skin, bone marrow, and liver biopsies had no physical evidence of GVHD. TA-GVHD was found in the HLA typing of the patient's family. This TA-GVHD case was considered to be a reduced immunity due to severe surgical stress or preoperative transcatheter arterial embolization (TAE), in view of the fact that he was transfused with fresh whole blood during the operation. TA-GVHD has frequently been reported in patients after open heart surgery, but also after hepatectomy. It is therefore necessary to take all available means to prevent it by restricting the use of blood preparations as much as possible, and if hetero blood transfusions are performed, blood should be irradiated prior to transfusion. PMID- 8007628 TI - Scanning electron microscopic observations of the arachnoid granulations in monkeys with cerebrospinal fluid hypotension. AB - The changes in arachnoid granulations following the depletion of cerebrospinal fluid (CSF) were investigated by scanning electron microscopy (SEM) and transmission electron microscopy (TEM). In the normal tissue, the arachnoid granulations located at the inner walls of the superior sagittal sinus and the straight sinus had bulging protrusions of various sizes, as viewed with the SEM. With TEM, the outermost cells covering the surface of the arachnoid granulations had "giant vacuoles" in the cytoplasm. With CSF hypotension, the arachnoid granulations were smaller in size and the outermost layer of cells were thinner. The vacuoles in the outer layer were not developed. In the apical region of the individual arachnoid granulations with CSF hypotension, the arachnoid cells were densely clustered under the endothelial cells. With recovery to normal CSF pressure, the arachnoid cells appeared to protrude between the endothelial cells covering the apical portion of the arachnoid granulation. PMID- 8007629 TI - Clinical studies of oral quinolone once daily in the treatment of lower respiratory tract infections. AB - The efficacy and safety of oral ofloxacin, 400 mg once daily, for the treatment of patients with lower respiratory tract infections were studied. The most common species recovered from the sputum specimens of these patients were Haemophilus influenzae, followed by Streptococcus pneumoniae (S. pneumoniae), Staphylococcus aureus (S. aureus), Gram positive cocci unidentified, Pseudomonas aeruginosa (P. aeruginosa), Morexella catarrhalis, Streptococcus epidermidis, and another Haemophilus species in this order. All these bacteria were susceptible to ofloxacin except for one strain of methicillin resistant S. aureus. A satisfactory clinical outcome was achieved in 34 of 40 patients (85%). It is concluded that ofloxacin, 400 mg once daily, is useful for patients with respiratory tract infections. PMID- 8007630 TI - Stage I adenocarcinomas of the lung: survival of females and males. AB - Seventy-two cases of Stage I lung adenocarcinomas in females were analyzed and compared with 84 cases in males, all of which were surgically resected at the National Kyushu Cancer Center Hospital in Japan. The females with Stage I adenocarcinomas had a tendency, that was not significant, towards a longer survival than the male patients. When subdivided by age into less than 50, between 50 and 70, and more than 70 years-old, the female patients had a tendency, that was not significant, towards a longer survival in each group. In each age group, the ratio of smokers to non-smokers was higher in the males. The female group of ages 50 to 70 had the best 5-year survival rate. By multiregression analysis, age was found to be the most important factor for improved survival. The results indicate that a hormonal factor in Stage I lung adenocarcinoma does not influence survival. PMID- 8007631 TI - A granular cell tumor of the buccal mucosa--a case report. AB - In the oral region, granular cell tumors often occur in the tongue, but rarely in the buccal mucosa. A case of granular cell tumor in the right buccal mucosa of a 74 year-old female is described. An elastic-hard solid mass about 1 cm in diameter was palpated under the right buccal mucosa. It was well-defined from the proximal tissues and adhered to part of the buccal mucosa. As a result of a biopsy, the diagnosis of a granular cell tumor was made. The tumor was resected together with the surrounding tissues under local anesthesia. Histopathological examination revealed large tumor cells with eosinophilic, PAS-positive fine granules under the hyperplastic epithelium. The granular cells stained negatively with PTAH, but positively with S-100 protein. Electron microscopic observations revealed a number of lysosomes of various sizes and densities within the cytoplasm of the tumor cells. PMID- 8007632 TI - CSF beta-endorphin levels in pediatric neurologic disorders. AB - To investigate pediatric brain impairment, beta-endorphin levels, one of the opioid peptides that modulate human high cortical functions, were measured in cerebrospinal fluid (CSF). The study included 19 patients with infantile autism, 3 patients with Rett syndrome, 6 patients with infantile spasms, 16 patients with aseptic meningitis, and 23 age-matched controls. In the control group, the CSF beta-endorphin concentrations were negatively correlated with increasing age. There was no correlation between body temperature and the levels, and no significant difference in the levels according to sex. In infantile autism, the CSF level was not significantly different from that in controls. In Rett syndrome, it was significantly higher, while in infantile spasms it was lower than in controls. In aseptic meningitis, the CSF beta-endorphin level was significantly higher than in controls. The alterations in CSF beta-endorphin levels may play a role in these neurologic disorders and/or in central nervous system (CNS) infections. PMID- 8007633 TI - Effects of benzamide derivatives on dopamine release from striatal slices of rats. AB - The effects of the benzamide derivatives, (-)-sulpiride, sultopride and nemonapride, on spontaneous and electrically evoked dopamine (DA) release from striatal slices of rats were investigated. Nemonapride at concentrations of 100 nM or higher caused a dose-dependent increase in spontaneous DA release from the slices. (-)-Sulpiride and sultopride had little effect on spontaneous DA release. The electrically evoked DA release was enhanced by (-)-sulpiride at concentrations of 100 nM or higher in the superfusate and reduced by nemonapride at 100 nM or higher. Sultopride caused a small increase in the evoked release of DA. The different activities of these drugs on DA release may account for the different clinical results they produce. PMID- 8007634 TI - [Therapeutic risks in nursing. How can one anticipate all the consequences?]. PMID- 8007635 TI - [Medicine and nursing: risky interactions. Respecting the same scale of values. Interview by Monika Brechbuhler]. PMID- 8007636 TI - [Nursing care and political engagement. A different attitude to life. Interview by Fred Arm]. PMID- 8007637 TI - [Risks at the neonatal unit]. PMID- 8007638 TI - [Caring for the children in the slums of Manila. The barefoot nurse]. PMID- 8007639 TI - [The effect of emotions on the organism. To the very end, hope]. PMID- 8007641 TI - [The risk of morals]. PMID- 8007640 TI - [Waste, a resource]. PMID- 8007642 TI - [The healing effect of eros and tenderness. Sexuality: a relational risk for nursing personnel and patients]. PMID- 8007643 TI - [Newest treatment modalities: care of children with burns]. PMID- 8007645 TI - [Being able to take a risk]. PMID- 8007646 TI - [Ambulatory Surgery]. PMID- 8007644 TI - [A study trip across Russia. A look at Russian hospitals]. PMID- 8007647 TI - [Infection control and quality assurance in the hospital]. PMID- 8007648 TI - [Bed making in the bedding center or as hotel beds]. PMID- 8007649 TI - [The clinical importance of pelvic injuries]. PMID- 8007650 TI - [Human and nursing models. 4. Johnson's behavior system model--selection and introduction of a nursing model]. PMID- 8007651 TI - [Interactions between residents and nurses in old age homes]. PMID- 8007653 TI - [On getting over insults]. PMID- 8007652 TI - [What is help--supervision?]. PMID- 8007654 TI - Enterocecocolitis associated with Escherichia coli and Campylobacter-like organisms in a hamster (Mesocricetus auratus) colony. AB - Sporadic diarrhea and weight loss were observed in a breeding colony of Syrian hamsters during a 2-year period. Thirteen adult hamsters with diarrhea, anorexia, and weight loss were examined. Histologic lesions consisted of diffuse nonsuppurative enterocecocolitis and multifocal epithelial proliferation in the cecum and colon. Goblet cell hyperplasia was extensive in the colonic mucosa of many hamsters. The hamsters in this colony had not been treated with antibiotics nor was Clostridium difficile isolated from any of the hamsters. In contrast to typical proliferative ileitis in hamsters, most hamsters involved in this outbreak were mature adults rather than weanlings, and lesions were predominantly inflammatory rather than proliferative and involved small intestine, cecum, and colon rather than ileum. The isolation of beta-hemolytic Escherichia coli and demonstration of Campylobacter-like organisms by transmission electron microscopy and Warthin-Starry staining suggest that these two agents were involved in the pathogenesis of this disease. Further studies, however, are needed to investigate the pathogenesis of this enteric syndrome in hamsters. PMID- 8007655 TI - Low-virulent mouse hepatitis viruses exhibiting various tropisms in macrophages, T and B cell subpopulations, and thymic stromal cells. AB - Functional or cellular immunodeficiencies have been reported to result from various pathogenic mouse hepatitis virus (MHV) strains. Moreover, low-virulent MHV strains can reduce the ability of mice to seroconvert to other antigens or viruses. To determine the importance of low-virulent MHV strain tropism in immune cells, as a mechanism involved in the induction of immunodeficiencies, peritoneal exudate cells, T and B cell subpopulations, and thymic stromal cells were infected with low-virulent MHV-D, MHV-K, and MHV-N and pathogenic MHV-3 viral strains. Cell viability, percentages of viral protein-expressing cells, and virus titers have been analyzed. On the basis of our findings, low-virulent MHV viral strains exhibit various tropisms in macrophages, B lymphocyte subpopulations, or thymic stromal cells when compared with the more virulent MHV-3 serotype. All MHV strains tested have replicated in peritoneal exudate cells of C57BL/6 or A/J mice. Low-virulent MHV-N and pathogenic MHV-3 strains showed higher tropism for peritoneal exudate cells than low-virulent MHV-K and MHV-D strains. Likewise, MHV N and -3 serotypes expressed higher tropism than MHV-D or -K serotypes for thymic stromal cells and B lymphoid cells. No tropism for T lymphocytes, however, was detected with MHV except when in contact with previously infected thymic stromal cells. These results raise the problem of immunologic disorders resulting from viral replication in immune cells in mouse colonies subclinically infected with low-virulent MHV strains. PMID- 8007656 TI - Seroepidemiologic studies of cytomegalovirus infection in a breeding population of rhesus macaques. AB - A protein immunoblot (western blot) assay was developed for detection of IgG and IgM antibodies to cytomegalovirus (CMV) in banked serum and was used to study the epidemiology of infection in a breeding population of rhesus macaques. All juveniles and adults were antibody-positive to CMV. Repeated samples from 1990 born infants (n = 28) over a 12-month period allowed retrospective assessment of CMV seroconversion. Most infants (23 of 25 seroconversions) were apparently exposed to CMV during their first year of life. The IgM testing permitted identification of seroconversion time points in eight infants. Risk factors that significantly affected seroconversion probabilities in the study population were not found. Cytomegalovirus-free rhesus macaques are potentially valuable for viral teratology and pathogenesis research projects; however, present epidemiologic findings suggest that establishment of CMV-free colonies will be difficult in conventional settings. PMID- 8007657 TI - Use of vancomycin hydrochloride for treatment of Clostridium difficile enteritis in Syrian hamsters. AB - As part of an 18-month carcinogenicity study, 680 Syrian hamsters (Mesocricetus auratus) received daily gavage doses of fenazaquin, an experimental miticide. Mortality associated with severe enteritis was noticed beginning when the hamsters were 4 months old and ranged from one to five deaths per month until the hamsters were about 10 months old, when 41 deaths occurred in a 1-month period. Ante- and postmortem findings were consistent with those reported for antibiotic induced enteritis in hamsters. Clostridium difficile was isolated from 12 of the 13 samples of cecal contents analyzed. Toxin assays of C. difficile isolates collected from 11 affected animals were positive for both cyto- and enterotoxins. Daily oral administration of vancomycin hydrochloride at a dose of 20 mg/kg was initiated when the hamsters were about 10 months old. Deaths due to C. difficile enteritis were significantly decreased within 2 weeks, and treatment was continued for 3 months. A trial withdrawal period for a subset of 64 hamsters (approximately 16% of the total population) was initiated to evaluate survival after discontinuation of the antibiotic treatment. Clostridium difficile enteritis recurred within 2 weeks and caused 19 deaths during the next month; therefore, these hamsters were returned to daily vancomycin treatment for the remainder of the study. With the exception of severe gaseous distention of the ceca, which caused death in 17 (< 4% of the total population) of the affected hamsters, vancomycin treatment did not cause any major adverse effects.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8007658 TI - Breeding of the gad-mdx mouse: influence of genetically induced denervation on dystrophic muscle fibers. AB - A new double mutant mouse strain, gad-mdx, was established. The transmission of mdx and gad genes was monitored by determining their chemical markers, creative kinase activity and phosphoglucomutase-1 isoenzyme, respectively, in blood samples. This new strain was characterized by high creatine kinase activity in the plasma, lack of dystrophin in the muscle, and the presence of axonal swellings in the neural tissue. Although the body weight and the limb muscle size of the mutant mice were significantly lower than those of either gad or mdx mice, the clinical signs were not evident until the animals were 80 days old. After that time, the disease followed the course seen in the gad strain, and muscle weakness was exhibited in the advanced stages. Histologic examination revealed that the prevalence of muscle fiber necrosis, a deleterious consequence of the mdx gene, was significantly lower in the double mutant strain than in the mdx strain. These results supported the idea that small-caliber muscle fibers, which are induced by gad gene expression, are resistant to dystrophic necrosis. We believe that this double mutant strain will be valuable for the analysis of neural influence on diseased muscle fibers, and that it will also provide an opportunity for the testing of new therapeutic strategies for human Duchenne muscular dystrophy. PMID- 8007659 TI - The character of endogenous retrovirus in pancreatic beta-cells of NOD mice. AB - The character of retrovirus type C in NOD mouse pancreatic-beta-cells was investigated. First, the in vitro response of retrovirus type C to glucose stimulation was examined. When the pancreatic islets of control NON mice were observed with an electron microscopy retrovirus types C could not be detected in the beta-cells with or without glucose stimulation. Retrovirus type C particles and intracisternal type A particles (IAPs) in NOD mouse pancreatic beta-cells increased by glucose stimulation, but the increase in retrovirus type C differed from that of IAPs. The clusters of retrovirus type C were found in some beta cells, whereas IAPs were scattered in beta-cells. Next, we investigated the expression of retrovirus type C transcript in NOD mouse pancreatic islets. From polymerase chain reaction analysis using two primers of retrovirus type C designed from a conserved U3 region, a major product was found to be endogenous polytropic retrovirus (Pmv). The subcloned PCR probe and oligonucleotide probes specific for Pmv and modified polytropic retrovirus were used for Northern blot analysis. Pancreatic islets from NOD and NON mice (control mice) contained 8.4-kb and 3.0-kb Pmv transcripts. The quantity of transcripts of Pmv in NOD mouse pancreatic beta-cells were the same as that in NON mice. The transcript level of islets was much higher than those of thymus and liver. The appearance of retrovirus type C particles in beta-cells of NOD mice may involve the mechanisms by which diabetes is generated in NOD mice. PMID- 8007660 TI - Group housing: meeting the physical and social needs of the laboratory rabbit. PMID- 8007661 TI - A cytotoxicity assay for Clostridium spiroforme enterotoxin in cecal fluid of rabbits. AB - Clostridium spiroforme enterotoxin-mediated diarrhea can be a common cause of mortality among weanling age rabbits. Definitive diagnosis of this disorder requires detection of the causative enterotoxin. Using filtered cecal supernatant from necropsy specimens, antibodies to C. spiroforme and its products and Vero cells, a cytotoxicity assay was performed on 22 rabbits with clinical signs and lesions consistent with C. spiroforme enterotoxin-mediated diarrhea. A cytotoxic effect was detected, generally within 4 h, in 18 of 22 rabbits. The cytotoxic effect was blocked by preincubation of the cecal material with antibodies to C. spiroforme and its products. Culture of cecal contents and smears of cecal contents identified C. spiroforme in 10/22 and 12/22 cases, respectively. This cytotoxicity assay provided a rapid and sensitive method for diagnosing C. spiroforme enterotoxin-mediated diarrhea. PMID- 8007662 TI - Technique for placement of chronic third cerebroventricular cannula in female goats (Capra hircus). AB - A practical method for chronic catheterization of the third cerebroventricular space in goats was developed by using a stereotaxic device. In female goats of various ages and weights, a stereotaxically mounted drill was positioned at an angle of 11.5 degrees with the tip of the drill bit located at a skull reference point 2 to 3 mm rostral to the posterior border of Bregma (intersection of the coronal with the sagittal sutures). The hole that was drilled served as the guide for a tight-fitting cannula, which was 20-gauge stainless steel with a stylet. The cannula was advanced by hand to a depth of approximately 40 mm from the top of the skull, positioning the cannula tip in the anterior region of the third ventricle anterior to the massa intermedia. Copious flow of cerebrospinal fluid verified appropriate positioning. The cannula was anchored with dental acrylic and a subcutaneous port system attached via plastic tubing. Cannula placement was assessed after surgery by use of fluoroventriculography. Cannula patency was maintained for 23 months. Minimal complications were seen, maintenance was minimal, and animals were allowed complete freedom of movement with no requirement for jackets or wraps and were used in several consecutive studies. No anesthetic complications were noticed. PMID- 8007663 TI - Surface area to volume relationships of snakes support the use of allometric scaling for calculating dosages of pharmaceuticals. AB - Metabolic scaling is used to estimate pharmaceutical dosages for snakes because few pharmacokinetic studies have determined optimum dosages. The question arose as to the validity of the assumption of metabolic scale among snakes because they have such a cylindrical shape. The surface area to volume relationships of a group of animals is a major portion of the metabolic scaling exponent of 0.75. An assumption inherent in scaling pharmaceutical dosages for snakes is that there is not a shape change with a size change, or that scaling of the surface area to volume has an exponent of 0.66. One hundred forty snakes, 106 Colubridae and 34 Boiidae, were weighted, their volume was determined by water displacement, and the snakes were measured. Geometric formulas were used to calculate surface area and volume of each snake. Surface area to volume relationship was nearly isometric, with a scaling exponent of 0.64, supporting the use of metabolic scaling for estimating pharmaceutical doses. PMID- 8007664 TI - Blood collection and surgical procedures for the laboratory opossum (Monodelphis domestica). AB - Procedures have been developed for collecting blood samples from the laboratory opossum (Monodelphis domestica) and for conducting survival surgery on adults. Blood samples up to 1 ml were collected routinely by cardiac puncture of animals anesthetized by inhalation of methoxyflurane or halothane with minimal risk; however, halothane required more careful monitoring. Surgical procedures such as partial hepatectomy unilateral hysterectomy, and tail wound repair were safely accomplished on animals anesthetized with methoxyflurane. Other surgical procedures including enucleation and intra-abdominal vasectomy were carried out successfully with an inhalation/injection (pentobarbital-atropine-ketamine) protocol that was successful also for recipient surrogate females in embryo transfer experiments. PMID- 8007665 TI - Diagnostic exercise: thickened auricular pinnae in a Sprague Dawley rat. PMID- 8007666 TI - Preretinal arteriolar loops in rats. PMID- 8007667 TI - The efficacy of a dirty bedding sentinel system for detecting Sendai virus infection in mice: a comparison of clinical signs and seroconversion. PMID- 8007668 TI - Periocular and urogenital lesions in mice (Mus musculus) chronically infected with Trypanosoma brucei. PMID- 8007669 TI - Vitamin B-responsive cystic enteritis in a pigeon colony. PMID- 8007670 TI - Lectin histochemical changes of colon goblet cell mucin in rabbit mucoid enteropathy. PMID- 8007671 TI - Identification of laboratory animals by using affinity immunoblotting. PMID- 8007672 TI - Immunohistochemical detection of localized Sendai virus antigen in preserved mouse tissue. PMID- 8007673 TI - Local hyperthermia abrogates the anti-immunotherapeutic effect of interleukin-8. AB - The therapeutic efficacy of cellular immunotherapy depends not only on the anti tumor activity of the administered effector cells but also on their ability to gain access to the tumor by extravasation. Although interleukin-8 (IL-8) has been shown to prevent the vascular leak associated with IL-2, it also abrogates the anti-tumor effect of IL-2. We undertook these studies to determine if LHT could abrogate the anti-immunotherapeutic effect of IL-8, since IL-8 inhibits leukocyte adhesion. C57BL/6 mice were divided into four groups of six animals each after induction of MCA-105 fibrosarcoma inoculated into the right hindlimb on day 0 and were treated beginning on day 3 as follows: no therapy, IL-2 alone (1.02 x 10(6) IU ip tid on days 3-7), IL-2 + IL-8 (9.6 ng ip tid on days 3-7), and IL-2 + IL-8 + LHT (45C x 15 min on days 3, 5, and 7). Tumor growth was measured on days 10-21 and analyzed by Wilcoxon rank-sum analysis. IL-2 reduced tumor growth significantly (P < .05) compared to no therapy, and IL-8 abrogated the anti-tumor effect of IL-2, resulting in tumor growth in animals receiving IL-2 + IL-8, similar to the no therapy group (P > .05). However, addition of LHT to IL-2 + IL 8 resulted in significantly (P < .05) less tumor growth than no therapy or IL-2 + IL-8. Activity of the mice was scored as an indicator of systemic toxicity. We found that IL-8 was able to increase the activity (P = .07) of the mice when administered with IL-2. These results suggest that IL-8 may protect the tumor bearing animal from the systemic toxicity of IL-2, while LHT abrogates the anti immunotherapeutic effect of IL-8. PMID- 8007674 TI - An aid to bladder dissection during radical hysterectomy following pelvic irradiation. PMID- 8007675 TI - Phylloides tumor of the breast: a report of 14 cases. AB - The objective of this retrospective study is to determine the role of radiation therapy in the management of benign phylloides tumors. Fourteen patients with a diagnosis of benign phylloides tumor (PT) and registered at the Princess Margaret Hospital are included in the study. Definitive surgery consisted of either lumpectomy in seven patients or mastectomy in the other seven patients. One patient died of her disease, and the remaining patients had no evidence of disease at last follow-up (median 38.4 months). Among these 13 patients, 4 had at least one recurrence and the recurrence rate was higher for the group who underwent lumpectomy (43% compared with 28%). One patient was treated by lumpectomy and adjuvant radiation therapy, and had no subsequent recurrence (follow-up time 35.5 months). The role for radiation therapy in the management of this disease remains unclear. PMID- 8007676 TI - Regional chemotherapy in the canine liver. AB - Using a fluorometric assay, mean drug levels of Adriamycin were significantly higher in the normal canine liver following bolus injection of this drug via the hepatic artery or portal vein as compared to hepatic tissue levels following systemic intravenous administration (P < 0.001). However, the variations in tissue levels observed after hepatic artery (+/- 16.8 mcg/gm tissue) or portal vein (+/- 21.1 mcg/gm) infusion were significantly wider than those observed after systemic (+/- 1.3 mcg/gm) administration (P = 0.03). Using C14-labeled drugs, regional infusion of Adriamycin through the hepatic artery or portal vein resulted in significantly higher mean drug levels in the liver than after systemic intravenous administration, but the difference was more pronounced with bolus infusion of the drug than 1-hour infusion. 5-FU bolus or 1-hour infusion in the hepatic artery resulted in significantly higher mean drug levels in the liver compared to peripheral intravenous administration, but this was not so with the 3 hour infusion. The above experiments confirm previous studies that regional chemotherapy results in higher drug levels in the regional tissues compared to systemic administration. They also: (1) demonstrate the spotty drug distribution in the regional tissues after regional administration, a potentially correctable problem, and (2) suggest that the advantage of intra-arterial infusion may be more pronounced within a certain range of infusion times. PMID- 8007677 TI - Esophageal carcinoma simultaneously associated with gastric carcinoma: analysis of clinicopathologic features and treatments. AB - Among 1,420 patients with thoracic esophageal carcinoma, 85 (6.1%) had synchronous gastric carcinoma. Seventy-two patients (84.7%) underwent esophagectomy. Their operative mortality and prognosis were similar to those without gastric carcinoma. Among them, 25 patients, of whom the majority had advanced gastric carcinoma, underwent transthoracic esophagectomy with total gastrectomy (group A); eight died of esophageal cancer and four of gastric cancer. Forty-six patients, of whom the majority had gastric carcinoma in an early stage, underwent esophagectomy and esophagogastric anastomosis following partial gastrectomy or local treatment for gastric carcinoma (group B). None of the group B patients had recurrent gastric carcinoma. The operative burden was larger in group A. The 5-year survival rate for groups A and B were 38.8% and 23.0%, respectively. Esophagectomy and esophagogastric anastomosis after limited treatment for gastric carcinoma is an adequate treatment for the majority. However, esophagectomy and total gastrectomy are recommended for patients with advanced gastric carcinoma. PMID- 8007678 TI - Effect of the combination of hyperthermia and irradiation on human colon cancer cells. AB - The combination of hyperthermia and radiation is considered to have a synergistic effect on mammalian cells, which depends on temperature and duration of time of the hyperthermia and on the sequence in which the modalities are given. The response of cultured colon cancer cells to hyperthermia and ionizing radiation was evaluated using the flow cytometry method by measuring DNA damage. The enhanced DNA damage after combined treatment with hyperthermia and irradiation was recognized after both sequences: heat followed by radiation as well as radiation followed by heat. The results demonstrated that the sequence of radiation plus heat produced more DNA damage on colon cancer cells than did the reverse order. The clinical application of these results is discussed. PMID- 8007679 TI - p53 immunoreactivity in carcinosarcoma of the esophagus. AB - The case of a primary esophageal carcinosarcoma, shown to express p53 protein, is presented. The patient, a 57-year-old male, presented with fever, weight loss, and clubbing, but without swallowing difficulties. A large intraesophageal tumor was found on radiologic imaging, and sarcoma was diagnosed on esophagoscopic biopsy. Despite total esophagectomy and adjuvant chemo-radiotherapy, pleural metastases developed 3 months postoperatively. Histologically, the tumor was composed of epithelial and sarcomatous elements. Using monoclonal and polyclonal anti-p53 antibodies, p53 protein was distributed heterogenously throughout the sarcomatous elements of the primary tumor. Immunoreactivity was also found in regional lymph node metastases. These observations further implicate the p53 tumor suppressor gene in the pathogenesis of human esophageal cancers. PMID- 8007681 TI - Serum CA 125 concentrations in patients with benign ovarian tumours. AB - Serum CA 125 concentrations have been measured in 115 patients with histologically confirmed nonmalignant pelvic disease, that is, serous cystadenoma (n = 56), mucinous cystadenoma (n = 14), fibroma (n = 33), thecoma (n = 8), and Brenner tumour (n = 4). Increased CA 125 concentrations (> 35 KU/L) were found in 14 patients, with a range of 46-891 KU/L, a mean of 205 KU/L, and a median of 97 KU/L. The highest values were found in patients with ascites. Serial measurements in one patient showed a fall in the 2 days immediately after surgery, over the next 3 days showing a two- to three-fold increase, followed by a slow return to normal over the next 7 weeks. Elevated CA 125 levels may not indicate ovarian malignancy and do not differentiate between benign and malignant pelvic masses. PMID- 8007680 TI - Munchausen's syndrome and cancer. AB - Munchausen's syndrome is a chronic factitious disorder characterized by frequent hospitalizations, self-inflicted injuries, and dramatic medical histories. People with this condition assume the role of a sick patient and submit to unnecessary invasive, painful, and even dangerous medical procedures. In review of the literature, there have been four reports of patients feigning oncological disease. We admitted a 27-year-old woman who had undergone operative insertion of a Port-A-Cath and multiagent chemotherapy for "advanced ovarian cancer." Physicians should be aware of Munchausen's syndrome in order to avoid costly medical procedures and unnecessary operations and to stop the patient's vicious circle of pathological lying and self-inflicted injury. PMID- 8007682 TI - Short-term intrahepatic FUdR infusion combined with bolus mitomycin C: reduced risk for developing drug resistance. AB - This study evaluates tumor response, survival, and development of resistance to HAI chemotherapy, comparing a combination of bolus MMC and short duration FUdR to short duration FUdR alone or to long duration FUdR alone, using a rat hepatic metastases model. After intrasplenic injection of 10(7) K12/TRb colon cancer cells in BD-IX rats on day 0, hepatic metastases were evaluated and HA catheters were placed on day 14. The response was determined on day 28. Chemosensitivity of the hepatic metastases after HAI treatments was determined using the MTT assay. Bolus MMC with short duration FUdR as well as long-term FUdR alone provided better hepatic tumor response and survival than short-term FUdR alone. However, bolus MMC with short duration FUdR decreased the acquired resistance to FUdR, compared to long-term FUdR, without causing resistance to MMC. These results provide a rationale for using short duration of FUdR in combination with other drugs. PMID- 8007684 TI - Prognostic factors in head and neck soft tissue sarcomas: analysis of 128 cases. AB - Soft tissue sarcomas make up a heterogenous group of rare malignant tumors originating from mesodermal tissues. Although there have been several improvements in diagnostic methods, staging, and treatment over the past few years, the prognosis of head and neck sarcomas remains worse than those sited at the trunk or extremities. The purpose of this retrospective study was to report the survival results of 128 consecutive patients with soft tissue sarcomas of the head and neck treated from 1953 to 1985. Of the 93 patients submitted to surgical resection, the procedure was considered radical in 67 patients. Of the operated group, 46 patients (49.5%) developed recurrence of disease. Thirty-two patients underwent further treatment (surgery, radiotherapy, or chemotherapy), and 14 patients were salvaged, giving the ultimate result of 65.6% disease control rate in the operated group. The univariate survival analysis showed no statistical difference (P > 0.05) according to age, race, sex, and site or histologic type of the tumor. Radicality of surgery was an important prognostic factor affecting survival (P = 0.0014 for disease-free interval and P = 0.0183 for overall survival). The multivariate analysis showed that the radicality of surgery and tumor histology were independent prognostic factors affecting recurrence. The same variables and age group were related to the risk of death. Every effort must be made to make an early diagnosis and a radical surgical resection of these tumors must be tried (except for embryonal rhabdomyosarcoma), because it offers the best chance for cure. PMID- 8007683 TI - Nephrectomy as a component of systemic treatment for renal cell carcinoma patients. PMID- 8007685 TI - Adult paratesticular sarcomas: a report of eight cases. AB - Eight adult paratesticular sarcomas seen at a Regional Cancer Centre over a 7 year period are described. There were three cases of rhabdomyosarcoma (RMS), three cases of leiomyosarcoma (LMS), and two cases of liposarcoma (LS). The RMS occurred in a younger age group (3rd decade) than the LMS and LS (6th and 7th decades). Most of our patients presented with advanced disease after orchiectomy at other hospitals, three with recurrent or residual disease and four with metastasis. The single patient with RMS who received intensive adjuvant therapy is free of disease at 84 months in spite of the advanced stage at presentation. All three patients with LMS had an unfavourable clinical course. Both the patients with LS had well differentiated (WD) tumours and presented with recurrences, one over several years, following initial local excisions. The necessity for early adequate surgical and adjuvant therapy and the need for a uniform treatment policy are discussed. PMID- 8007686 TI - Comparative endoscopic study of primary gastric lymphoma vs. gastric carcinoma. AB - The endoscopic records of 56 patients with primary gastric lymphoma and 120 patients with gastric adenocarcinoma (matched for age and sex) were compared with respect to site, extent, and type of tumor by endoscopy and biopsy results. Diagnosis of lymphoma was suspected on the basis of gross endoscopic appearance in 30 patients with 96% sensitivity. The endoscopic findings that achieved statistical significance in favor of lymphoma were extensive disease involving whole stomach, proximal stomach involvement, extension of tumor into duodenum, and the presence of volcano crater-like ulcers on polypoid lesions. Endoscopic biopsies were positive for lymphoma in 92% patients. Immunoperoxidase staining for leucocyte common antigen was positive in all the 24 patients with lymphoma where it was performed. We conclude that lymphoid origin of the stomach tumor may be suspected in one-half of the cases of primary gastric lymphoma by gross endoscopic findings. Multiple endoscopic biopsies are safe and highly sensitive and specific in the diagnosis of primary gastric lymphoma. PMID- 8007687 TI - Immunological profile changes following perioperative autologous vs. homologous blood transfusion in oncologic patients. AB - To determine the effect of perioperative blood transfusion on immunological parameters, T cells, T-cell subsets, and concanavalin A-induced suppression were measured in 25 patients with colorectal and breast cancer. During the operation, 15 patients received autologous blood and 10 patients had homologous transfusion. The immunological status was again determined after curative surgery. Before surgery, normal percentage of T lymphocytes, decreased ratios of helper/suppressor cells, and impaired con A-induced suppression were found. Following the operation, the helper and suppressor cell percentages reversed to normal, whereas the con A-induced suppression remained impaired. This change was significantly more pronounced in patients who received autologous blood transfusion than in the other group. Autotransfusion has an impact on immune parameters that might prove less detrimental to the clinical outcome in oncologic surgery than homologous transfusion. PMID- 8007688 TI - Quantitative evaluation of malignant potential of early breast cancer using high resolution image cytometry. AB - We have been testing two independent hypotheses which postulate that the malignant potential of early breast cancer can be objectively assessed by measuring nuclear features of the diagnostic-malignant cells (hypothesis I) and/or normal-appearing epithelial cells found in the vicinity of the carcinoma (hypothesis II). In preliminary experiments, we tested some of these hypotheses using historical samples and a high resolution image cytometry apparatus. Tissue sections were stained with our stoichiometric stain and over 60 nuclear features, primarily texture features describing the DNA distribution in the nuclei, were employed in the multivariate analyses. Data derived from measurements of ductal carcinoma in situ (DCIS) with and without the invasive component indicated that the malignant potential of these lesions can be estimated with a sensitivity and specificity of at least 80%. The analysis of the tissue surrounding an invasive breast carcinoma showed that the existing malignancy can be predicted solely from the measurements of normal nuclei (normal-appearing breast lobules) in more than 85% of patients. This result indicates that the analysis of benign tissues also could give prognostically valid information. These results can be greatly improved using larger sample sizes and other improvements, including technical improvements of the cytometry device. We believe that this approach can be developed into a practical diagnostic and prognostic tool for better management of early breast cancer. PMID- 8007689 TI - Pathological and biological relevance of cytophotometric DNA content to breast carcinoma genetic progression. AB - Correlating cytophotometrically detectable genetic alterations to events of known biological and pathological significance in breast carcinoma has been challenging, in large part owing to the difficulty in isolating and analyzing premalignant (i.e., hyperplastic) or preinvasive (i.e., in situ carcinoma) lesions. This problem may be addressed by using histologically directed evaluation of intact, paraffin-embedded tissue sections. Using image cytophotometry in preserved sections, we have identified clonal DNA content abnormalities (i.e., aneuploidy) in up to three-fourths of preinvasive breast carcinomas. Moreover, comparison of ploidy determinations between residual in situ and corresponding invading neoplastic populations suggests that host invasion is accompanied by measurable DNA content shifts in many cases. Image cytophotometric DNA content abnormalities are also detectable in florid/atypical proliferative lesions, albeit less frequently (-25% of cases) and to a lesser extent (i.e., near-diploid) than in situ carcinomas. Taken together, these findings imply an association between clonal DNA content aberrations and histologic disease progression. Although the sensitivity of cytophotometric ploidy assessments in tissue sections is limited by nuclear sectioning artifact and overlap, the presence of genomic instability in precursor lesions is supported by evidence of individual chromosome aneuploidy, which can be demonstrated in tissue sections by interphase cytogenetics with fluorescent, centromere-specific probes. Further, presence of intra-tumoral clonal DNA content heterogeneity is confirmed by cytogenetic studies showing co-existing near diploid chromosome number modes in many tumors with hyperdiploid stemlines. Karyotypic stemline analyses imply polyploidization events are an important mechanism of clonal evolution leading to genetic heterogeneity.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8007690 TI - Biomarkers in early breast neoplasia. AB - Early breast neoplasia may be defined in many ways. Any non-invasive or invasive but nonmetastatic breast cancer qualifies as early neoplasia in the sense that they are non-lethal. Before we can prevent lethal breast cancer, we must gain a better understanding of the biological abnormalities underlying its development and progression. Many studies into the mechanisms of breast cancer evolution have evaluated potential precursor lesions (e.g., proliferative disease without atypia [PDWA], atypical ductal hyperplasia [ADH], and ductal carcinoma in situ [DCIS]) for genetic alterations known to occur in fully developed invasive carcinomas. This approach has shed some light on events which may be important in early malignant transformation, including the observations that overexpression of the c erbB-2 oncogene and mutations of the p53 tumor suppressor gene are present in significant subsets of DCIS, but not PDWA or ADH. This approach is limited by our incomplete knowledge of cancer genetics. However, there is more to learn by evaluating known cancer-associated genes in potential precursor lesions using established techniques such as immunohistochemistry and in situ hybridization. Until recently, technology could not detect unknown genetic abnormalities in microscopic lesions such as PDWA, ADH, or DCIS. Now, PCR-based techniques have the theoretical ability to detect novel tumor promoter and suppressor genes in clinical samples of these very small lesions. For example, suppressor-type genes may be detected using comprehensive mapping probes to identify loss of heterozygosity in PCR-amplified DNA extracted from a few hundred cells microdissected from either fresh or archival tissue.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8007691 TI - Cytogenetic profiling using fluorescence in situ hybridization (FISH) and comparative genomic hybridization (CGH). AB - Fluorescence in situ hybridization (FISH) and comparative genomic hybridization (CGH) allow cytogenetic analyses of primary tumors without culture. CGH allows detection and mapping of allelic imbalance by simultaneous in situ hybridization of differentially labeled tumor (green fluorescing) and normal DNA (red fluorescing) to a normal human metaphase spread. Regions of increased or decreased copy number in the tumor are mapped onto the normal metaphase chromosomes as increases or decreases in the green to red fluorescence ratio. This technique gives a comprehensive assessment of gene dosage imbalance throughout the tumor. However, it is limited, at present, to fairly large tumors containing few normal cells. FISH, on the other hand, allows analysis of DNA sequence copy number at specific loci in single nuclei. A wide variety of DNA probes is available for FISH, including chromosome-specific probes which hybridize to alpha-satellite pericentromeric DNA regions (to detect changes in specific chromosome copy number and overall ploidy) and specific locus probes targeting 20-150 kilobase sequences (to detect specific amplifications, deletions, breakpoints, or rearrangements). FISH using these probes has been applied to interphase nuclei in touch preparations, smears from fine needle aspirates, and thin (< 6 microns) and thick (> 20 microns) sections cut from formalin-fixed, paraffin-embedded tissue. Analysis of thick sections allows accurate actual signal enumeration within the histological context. This approach may allow analysis of subtle premalignant, early malignant, and infiltrating tumors in which malignant cells must be differentiated from nonmalignant cells.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8007692 TI - Intraepithelial and postinvasive neoplasia as a stochastic continuum of clonal evolution, and its relationship to mechanisms of chemopreventive drug action. AB - The progression of intraepithelial and postinvasive neoplasia depends on the occurrence of clonal evolution, defined as the continuous development of mutations and selective clonal expansions in the neoplastic cell population. The two continuously repeating events of clonal evolution, mutation and clonal expansion, occur at unpredictable times and locations. Therefore the neoplastic process is best characterized as a stochastic, i.e., probabilistic, continuum. The rate of intraepithelial neoplastic progression is continuously driven by the dosage level of exposure to mutagens and mitogens. For example, in chronic smokers the length of time before development of lung cancer depends on the number of cigarettes smoked per day. A commonly held misconception is that human carcinogenesis develops after an initial short period of mutation followed by a long period of stimulated proliferation (the multistage model). This incorrect idea derives from the sequential nature of the consecutive two- or three-step operational protocols imposed on experimental animal models by the experimenter. In reality, human carcinogenesis develops as the result of simultaneous and continuous exposure to mutagens and mitogens over the entire period of tumor development. A recent example is the finding that the intraepithelial neoplasia of colorectal adenomas continuously progresses through serial waves of mutation and clonal expansion. The rational design of chemopreventive agents should be based on blocking the two parameters which continuously drive neoplasia: mutagenesis and mitogenesis. In addition to blocking exposure, chemopreventive agents may act at many points during activation and DNA adduction of mutagens, or during stimulation of the proliferation signal pathway by mitogens. Based on the chemopreventive strategy of blocking mutagenesis and mitogenesis, chemopreventive agents are classed as either antimutagenic or antimitogenic. A third class, the antioxidants, are both antimutagenic and antimitogenic, and operate by the common mechanism of breaking free radical chain reactions initiated by reactive oxygen species. In the program of the Chemoprevention Investigational Studies Branch, Division of Cancer Prevention and Control, National Cancer Institute, preclinical development of antimutagens, antimitogens, and antioxidants is well under way, and some of these agents are highlighted here. PMID- 8007694 TI - Oncogenes, breast cancer, and chemoprevention. AB - Perturbations of oncogenes in breast carcinoma include amplifications of the HER 2/neu and PRAD1 genes, as well as p53 mutations. Some of these lesions frequently appear in early cancers such as ductal carcinoma in situ and are stable as the tumors become invasive and metastasize. Thus these findings suggest that oncogene mutations may define a point of origin for a given breast cancer, and are fixed lesions during tumor progression. Such germline abnormalities may occur at the BRCA1, H-RAS VNTR, and p53 loci. The rational use of genetics may be to identify women at high risk for the development of breast cancer so that they may be enrolled in future chemoprevention trials. PMID- 8007693 TI - Molecular aspects of early stages of breast cancer progression. AB - It is clear that breast cancer progression is associated with inactivation of a number of different recessive oncogenes. The most widely evaluated tumor suppressor gene, p53, is mutated in approximately 30-50% of sporadic breast cancers. Mutations usually occur early in malignant progression. Loss of heterozygosity (LOH) studies have identified numerous chromosomal regions where other recessive oncogenes relevant to breast cancer may be located. Each LOH is seen in a varying proportion of breast cancers and may appear either early or late in progression. High-grade ductal carcinoma in situ (DCIS) and invasive carcinoma have similar genetic lesions, showing that aberrations can occur before invasive disease. Direct evidence that the same aberrations can be acquired later in progression comes from a study of multiple metastases from the same patient; other studies found that primary invasive cancers are characterized by marked intratumor heterogeneity for each lesion examined. The model we propose to account for these results hypothesizes that multiple genetic lesions can accomplish each phenotype required for malignancy (i.e., dysregulated proliferation, invasion, angiogenesis, etc.) and that, for a given tumor, at least one aberrant gene for each phenotypic change is stochastically selected. Biological heterogeneity of breast cancer results from the stochastic acquisition of various genetic aberrations. We further propose that the lymphocytic reaction in high-grade DCIS may select for aggressive tumor subpopulations capable of escaping immune surveillance. Another aspect of tumor heterogeneity may be the multiple mechanisms employed by various tumors to escape immune surveillance. PMID- 8007695 TI - Definition of regions of the human genome affected by loss of heterozygosity in primary human breast tumors. AB - We have undertaken a systematic study of primary human breast tumor DNA to identify and characterize frequently occurring somatic mutations. Loss of heterozygosity (LOH) has been the most frequent mutation in our panels of primary breast tumor DNA. It is currently thought that LOH reveals recessive mutations within the affected region of the genome. One goal of our studies has been to physically define the target genes revealed by LOH in primary breast tumors. We have focused our efforts on chromosome 17, finding five regions of the chromosome which are independently affected by LOH in breast tumors. Two apparent target loci are on chromosome 17p; one is the TP53 gene. The other is an as-yet undefined locus telomeric to the TP53 gene. Loss of expression of the nme1 gene on chromosome 17q in tumors was linked to patients with a poor prognosis (p = 0.018). Although a significant trend (p = 0.05) was found between LOH of the nme1 gene and loss of nme1 expression, no point mutations were found within the coding region of the nme1 gene by single strand conformational polymorphism (SSCP) or nucleotide sequence analysis. These and other results suggest to us that there may be potential tumor suppressor genes both centromeric and telomeric to the nme1 locus on chromosome 17q. PMID- 8007696 TI - Evidence for a positive role of transforming growth factor-beta in human breast cancer cell tumorigenesis. AB - To determine the biological role of transforming growth factor-beta (TGF-beta) in mammary carcinomas in vivo, estrogen-dependent MCF-7 cells were transfected with a mouse TGF-beta 1 cDNA. Growth characteristics in culture were not altered in the transfected cells. However, the MCF-7/TGF-beta 1 cells formed tumors in ovariectomized athymic mice in the absence of estrogen supplementation. Daily injections of human recombinant TGF-beta 1 supported tumor formation by wild-type MCF-7 cells in castrated nude mice in the absence of exogenous estradiol. In another approach to the same question, the effect of anti-TGF-beta antibodies on tumor formation by estrogen-independent MDA-231 cells was examined. The 2G7 IgG2b (2G7) antibody, which neutralizes TGF-beta 1, -beta 2, and -beta 3, blocked the formation of MDA-231 tumors at the injection site and lung metastases in nude mice. Inoculation of MDA-231 cells inhibited, while injection of 2G7 increased mouse spleen natural killer (NK) activity. 2G7 did not inhibit MDA-231 tumors and metastases in NK-deficient animals. Finally, medium conditioned by MDA-231 cells inhibited lymphocyte-mediated NK activity; this inhibition was abrogated by 2G7, but not by a control IgG2. These data support a positive role for tumor cell TGF beta in the maintenance and/or progression of mammary carcinoma cells in an intact host. PMID- 8007697 TI - Expression of estrogen receptor variants. AB - Recent data suggest that the expression of estrogen receptor (ER) variants may be common in clinical breast cancer. The significance of their expression is complicated by the fact that they are often coexpressed with wild-type ER in the same tumor. We have focused upon one such ER variant which lacks exon 5 within the hormone binding domain of the receptor. This deletion introduces a stop codon, resulting in a truncated ER of 40 kDa which is unable to bind hormone. We have been exploring the hypothesis that this variant may contribute to clinical antiestrogen resistance. Coexpression of the exon 5 variant along with wild-type ER in MCF-7 human breast cancer cells confers resistance to the commonly used antiestrogen, tamoxifen. In addition, we have observed that some metastatic breast lesions overexpress exon 5 ER deletional variant transcripts. We conclude that differences in the relative amounts of several ER variants in the same tumor may interact to determine hormonal responsiveness and metastatic behavior. PMID- 8007698 TI - Standardization and quality control of quantitative microscopy in pathology. AB - Standardization and quality control of quantitative microscopy techniques are distinct but related concerns. The first deals with the great variety of quantitative methods, measured features, and even response variables used in investigation of biological or clinical processes. The latter deals with reproducibility of results from those investigations across time and test performance sites. Though distinct, efforts for standardization and quality control are inherently interactive. Consensus on standard methods, instrumentation, and data analysis is hard to achieve in fields developing as rapidly as quantitative microscopy. Consensus is possible, however, on the issues that affect test performance and interpretation. For example, issues of specimen type, fixation, processing, and staining affect image cytometry just as they do flow cytometry. Raw data acquisition issues include area sampling rules and fidelity of optical and sensor systems (light wavelength, glare/stray light, lens aberrations, numerical aperture, depth of focus, scan precision, pixel spacing and depth, sensor linearity, and stability). Intermediate data issues are primarily related to image foreground/background segmentation techniques- automated versus manual, object-specific versus field-based. Data reduction and interpretation procedures also provide many roads for divergence from uniformity. Each of these issues must be considered in terms of its effect on comparability and utility of quantitative microscopy results. Quality control for quantitative microscopy is as important as standardization for its use in research programs and with clinical specimens. The sine qua non of quality control is comparison of experimental results against a known "correct" value to estimate accuracy, and against other experimental results to estimate precision.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8007699 TI - Development of breast cancer chemopreventive drugs. AB - Breast cancer is the second highest cause of cancer mortality (19%) estimated for U.S. women in 1993 and accounts for the highest proportion of new cancer cases (32%) in this population. The rate of documented cases increased during the early 1970s and again in 1980-87, probably due to early mammographic detection. Increased knowledge of personal risk may also have been a consideration; however, 60% of women diagnosed with breast cancer have no known risk factor(s), such as family history, early age at menarche, late age at menopause, nulliparity, late age at first live birth, socioeconomic status, contraceptive use, postmenopausal estrogen replacement, or high fat intake. To prevent cancer, one strategy undertaken by the NCI is cancer chemoprevention, or intervention with chemical agents at the precancer stage to halt or slow the carcinogenic process. An objective of the NCI, DCPC is to develop promising cancer chemopreventive chemical agents as drugs for human use. Briefly, the process begins with identification of potential agents (e.g., pharmaceuticals, natural products, minor dietary constituents) from surveillance and analysis of the literature and from in vitro prescreen assays. Data on both efficacy (i.e., biological activities that either directly or indirectly indicate inhibition of carcinogenesis) and toxicity are gathered these sources. Various criteria are used to select and prioritize agents for entry into the NCI, DCPC preclinical testing program. The program begins with battery of in vitro efficacy screens using both animal and human cells to select agents for further testing; agents positive in these assays are considered for further testing. In the assay used for breast cancer chemoprevention, 7,12-dimethylbenz(a)anthracene (DMBA)-induced mouse mammary organ culture, 64 chemicals have inhibited formation of hyperplastic alveolar-like nodules. A panel of organ-specific animal screening assays are then used to assess efficacy in vivo. Two assays relevant for breast cancer chemoprevention are inhibition of N-methyl-N-nitrosourea- and DMBA-induced rat mammary gland carcinogenesis. Of 89 agents tested, 29 have inhibited cancer incidence, multiplicity, or both in at least one of the mammary assays; 21 agents are currently on test. Highly promising agents are then placed in traditional preclinical toxicity tests performed in two species. Finally, the most promising and least toxic agents enter clinical trials. Phase I clinical trials are designed to investigate human dose-related safety and pharmacokinetics of the drug. Phase II trials are small scale, placebo-controlled studies designed to determine chemopreventive efficacy and optimal dosing regimens.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8007700 TI - Surrogate endpoints in chemoprevention of breast cancer: guidelines for evaluation of new biomarkers. AB - Markers of early events in the development of breast cancer are potential candidates for surrogate endpoints in chemoprevention trials. There are many such markers and the challenge is to identify truly relevant markers. If successful, surrogate endpoints offer several potential benefits in the conduct of prevention trials, including: shorter latency and hence shorter trials; reductions in size and cost of trials; and the opportunity to study prevention measures where use of primary outcomes would be excessively invasive or unethical. Although there are currently no validated surrogate endpoints for breast cancer, criteria for the discovery and validation of surrogates have been proposed. Putative surrogate endpoints should be biologically plausible, represent an early event in the causal pathway, be measurable by a standardized and reliable assay, and exhibit a dose-response. Perhaps most importantly, surrogates should statistically capture the effect of the intervention on outcome. The identification and establishment of a biomarker as a valid surrogate for cancer is a stepwise process that involves both smaller "transitional" studies and larger second-generation chemoprevention trials in which both primary outcome and putative surrogates are measured. Transitional studies are used to move new markers from the laboratory into use in human populations, and are designed to address specific questions of assay validity, treatment/marker associations, marker/disease associations, and inter- and intra-individual variability. Promising markers should be added to current and planned, large, traditionally designed chemoprevention trials in order to definitively address the issues of optimal representation, and to test the adequacy with which the marker(s) captures the effect of treatment on outcome.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8007701 TI - DNA flow cytometry measurements as surrogate endpoints in chemoprevention trials: clinical, biological, and quality control considerations. AB - DNA flow cytometric evaluation of S-phase fraction (SPF) is a strong and consistent predictor of relapse-free survival in the node-negative breast cancer patient. As such, it can be implicated as a marker of tumor aggressiveness and has been shown to be an independent predictor of outcome in a multivariate setting. Measurement of ploidy status is less well-defined as a marker of prognosis, but may be an important marker of response to therapy. Estimation of DNA ploidy and proliferative capacity by flow cytometry can be obtained from virtually any type of specimen, including fine needle aspirates, fresh or frozen material, as well as formalin-fixed, paraffin-embedded material, as long as there is a sufficient number of tumor nuclei for assay. Therefore, the assay has clinical relevance in predicting relapse, as well as providing flexibility for sample preparation. In addition, flow cytometric measurements are biologically relevant markers. In general, DNA index is a good estimate of total chromosome number. SPF, using sophisticated modeling algorithms, shows good correlation with thymidine labeling index and/or bromodeoxyuridine incorporation, two standard assays used to measure DNA synthesis in fresh tissue. Recently, preliminary data in locally advanced breast cancer have indicated that ploidy and/or S-phase may also be useful in predicting cellular response to chemotherapy. Although there is good justification for measuring these parameters, appropriate quality control and quality assurance measures must be incorporated into all aspects of the assay -from sample handling and preparation to interpretation of cell cycle and histogram data.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8007702 TI - The Multi-Center Morphometric Mammary Carcinoma Project (MMMCP) in The Netherlands: value of morphometrically assessed proliferation and differentiation. AB - The Multi-Center Morphometric Mammary Carcinoma Project (MMMCP) was set up to investigate the reproducibility and prognostic value of routine assessments of morphometric parameters [mean nuclear area (MNA), mitotic activity index (MAI), and multivariate prognostic index (MPI)] and cytometric features (DNA ploidy and index, % S-phase cells, as well as other cell cycle data) in comparison with classical prognostic parameters and steroid receptors. Thirty-four hospitals in six geographic regions participated. In 1988-1989, 3427 patients entered the study and morphometric assessments were made. An interim (1993) survival analysis indicated that MAI, MNA, and MPI are the strongest predictors of outcome. A Phase III randomized prospective multi-center trial [Premenopausal Morphometric Intervention Study (PREMIS)] using these endpoints was initiated in Europe to evaluate adjuvant [cyclophosphamide, methotrexate and 5-fluorouracil (CMF)] chemotherapy versus observation in morphometrically high risk (i.e., MAI > 10), premenopausal, lymph node negative (LN-) breast cancer patients. PMID- 8007703 TI - Breast cancer chemoprevention: studies with 4-HPR alone and in combination with tamoxifen using circulating growth factors as potential surrogate endpoints. AB - Fenretinide (4-HPR), a synthetic derivative of retinoic acid, has proven effective at inhibiting in vitro breast cancer cell growth and preventing the progression of chemically induced mammary carcinoma in rodents. Our group has made a particular effort with regard to this molecule in clinical studies aimed at evaluating its pharmacology, toxicity, and efficacy in breast cancer prevention. We have demonstrated that 4-HPR blood levels remain constant during administration for as long as 5 years, that the drug accumulates in the human breast, and that it induces a significant decline of plasma insulin-like growth factor-I (IGF-I) levels. To date, 2,972 Stage I breast cancer patients have been randomized to evaluate the efficacy of a 5-year administration of 4-HPR to prevent new contralateral primary breast cancers. Compliance to protocol and treatment is high and tolerability of the drug is good; only 51 women out of 1,397 (3.6%) had to interrupt drug intake due to toxicity. The only potential limitation to the extensive use of 4-HPR is diminished dark adaptation, which occurs in about one-fourth of the patients and is dependent on the decline of plasma retinol below the threshold level of 100 ng/ml. Plasma levels of (4 methoxyphenyl)retinamide (4-MPR), the principal metabolite of 4-HPR, which are higher in elderly women with a high percentage of adipose tissue, are the major determinants of the retinol decrease. However, about 50% of the patients with altered dark-adaptometry are asymptomatic and the alterations are promptly reversible upon drug discontinuation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8007705 TI - Clinical use of aromatase inhibitors in the treatment of breast cancers. AB - Estrogens are the major hormones supporting the growth of human breast cancer. Aromatization of androgen precursors in peripheral tissues, including the breast cancer itself, is the major source of estrogens in postmenopausal women. Therefore, inhibition of the aromatase enzyme offers an effective means of inducing regression of hormone-responsive breast cancer. Aminoglutethimide, the first and most widely tested aromatase inhibitor, suppresses estrogen production to the level of adrenalectomy and exerts an anti-tumor action comparable to other standard endocrine therapies such as tamoxifen. However, conventional doses of the drug (1000 mg daily) cause moderate toxicity and inhibit other critical cytochrome P-450 steroidogenic enzymes, thus requiring concomitant glucocorticoid administration. New non-steroidal, competitive aromatase inhibitors with greater selectivity and less toxicity are being developed. The second generation compound, fadrazole (CGS 16949), lowers estrogen production to a degree similar to aminoglutethimide (50-80%), but at much lower doses (approximately 2 mg daily) and is associated with minimal toxicity. Although not totally specific, this drug is sufficiently selective not to require simultaneous cortisol replacement. CGS 16949 has been shown to possess significant anti-tumor action in pilot studies and is currently being tested in Phase III trials. Recently, a third generation inhibitor, CGS 20267, has been found to have virtually complete selectivity for the aromatase enzyme. Furthermore, this drug suppresses estrogen biosynthesis to a greater extent (approximately 90%) than previously observed with other aromatase inhibitors. Such enhanced activity may lead to a superior anti-tumor action, and may extend the use of this drug to a variety of other conditions where optimal suppression of estrogen biosynthesis is desired. PMID- 8007704 TI - Selection criteria for breast cancer chemoprevention subjects. AB - Early phase chemoprevention trials differ from standard therapeutic clinical trials because asymptomatic, healthy people are treated with a potentially toxic intervention for a prolonged period of time. Current subject selection protocols have relied upon epidemiological methods to identify high-risk individuals. Most available data provide risk estimates for various individual risk factors, but few have reported risk estimates for combinations of risk factors. Selection criteria for the large tamoxifen intervention trial (NSABP P1) were developed from the work of Gail et al. [1]. The Gail model takes into account non-genetic factors (e.g., nulliparity, age at menarche, preexisting pathological conditions) and genetic factors (family history). Using a lifetime risk of 10% of developing breast cancer as a standard to intervene, NSABP P1 uses the Gail algorithm to select pre- and postmenopausal women for a primary intervention trial. This approach has been criticized for being insufficiently selective (i.e., all women > or = 60 yrs), but appears to be the best available method to select subjects for a chemoprevention trial. Other approaches have been based on identification of very high-risk women with acknowledged pathologic conditions [lobular carcinoma in situ, ductal carcinoma in situ (DCIS)]. Attempting to use these proliferative lesions as pathologic endpoints for drug effect has not been attempted. DCIS as a risk factor for tamoxifen intervention was excluded because of controversies over its management and because of frequent difficulties in distinguishing microinvasive from non-invasive lesions. Women treated for early stage breast cancer (Stage I) may be subjects for early stage chemopreventive interventions.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8007706 TI - The chemoprevention of breast cancer by reducing sex steroid exposure: perspectives from epidemiology. AB - Mitogenesis is a major driving force in neoplastic development. Blocking the effect of breast cell mitogens by reducing the actual exposure of the breast to these mitogens is an obvious strategy for breast cancer prevention. The ovarian hormones, estrogens and progesterone, are major effective (direct or indirect) breast cell mitogens. A woman's exposure to ovarian estrogens and progesterone is drastically reduced by the use of combination-type oral contraceptives (COCs), but the synthetic estrogen and progestogen in the COCs effectively replace ovarian estrogens and progesterone, so that breast cell exposure to these hormones is not decreased. Doses of estrogen and progestogen in modern COCs are close to the minimum attainable while still retaining both contraceptive efficacy and ovarian suppression (so that endogenous estrogen and progesterone do not add to the dose of estrogen and progestogen from the COC). Considerably lower effective breast cell exposure to estrogen and progestogen can, however, be achieved by using a gonadotropin-releasing hormone agonist (GnRHA) to suppress ovarian function and compensate for the resulting hypoestrogenemia with low-dose hormone replacement therapy. Compared to modern COCs, estrogen exposure can be reduced by approximately 60%, and progestogen dose by more than 80%. Such a contraceptive is predicted to reduce lifetime breast cancer risk by more than 50% if used for 10 years. The possibility that a practical contraceptive could achieve such a major benefit is shown by the dramatic decline in the incidence of both ovarian and endometrial cancer in young women in the U.S. over the last 3 decades--a direct result of COC use. PMID- 8007707 TI - Strategies for the application of biomarkers for risk assessment and efficacy in breast cancer chemoprevention trials. AB - Current chemoprevention trial designs based on epidemiological risk assessment and occurrence of cancer as an endpoint are inefficient and expensive. Novel biomarkers are needed to facilitate the development of chemopreventive interventions. The following four categories of biomarkers may be useful in prevention trials: histologic and morphometric markers; phenotypic markers of dysregulated proliferation, differentiation, and cell loss; specific oncogenes and growth regulators which are qualitatively or quantitatively altered in breast cancers; and markers of genetic and epigenetic instability. Some of these markers will be generally useful regardless of the chemopreventive approach used, whereas others may be uniquely useful in trials of specific chemopreventive agents [e.g., upregulation of progesterone receptor (PR) expression in response to tamoxifen]. The development of these markers requires three phases of study: "Phase I": assessing the prevalence of the putative marker in malignant and premalignant tissue from individuals who have developed breast cancer; "Phase II": assessing in vivo modulation of the biomarker by the proposed chemopreventive agent; and "Phase III": applying the proposed biomarker in larger-scale trials of chemopreventive agent in high-risk populations, either before or after the development of a primary breast malignancy. The use of these biomarkers may also allow identification of novel targets for chemoprevention. PMID- 8007709 TI - Heterogeneity of ductal carcinoma in situ of the breast. AB - Ductal carcinoma in situ (DCIS) now accounts for 20-30% of all newly diagnosed breast cancers in centers which use mammographic surveillance as a standard part of the examination. The majority of these DCIS lesions, at least in the United States, are of very limited size, with mean estimated extents of 8-20 mm, based on pathological examination. A small fraction of these are incidental microscopic features of the biopsy; the majority are detected on the basis of mammographic microcalcifications. These mammographically detected DCIS lesions are biologically heterogeneous, and this is reflected by their histology. Moreover, a number of recent independent studies have shown that the clinical outcome of patients, particularly those treated by breast conservation, is related to the presence of reproducible and identifiable histologic features, and possibly to certain immunohistochemically demonstrable gene markers as well. Regardless of the type of therapy, local recurrence in the breast is the most common and often the only site of failure after breast conservation therapy for DCIS. Although individual studies show some variation in the proportion of invasive to non invasive recurrence, equal numbers of invasive and non-invasive recurrences are most commonly noted. PMID- 8007708 TI - Clinical and histologic aspects of proliferative and non-proliferative benign breast disease. AB - It has been known for years that benign breast disease is correlated with an increased risk for the development of breast cancer. Over the years, there have been many studies linking histological changes in benign breast biopsies and subsequent risk of breast cancer. In many of these reports, there was no attempt to standardize criteria and often the patient population under study was relatively small. Over the past decade, three large groups have agreed to use the same definition of benign changes and a unified set of criteria for the diagnosis of these lesions. The results from these three groups [Nashville, Nurses Health Study (NHS), and the Breast Cancer Detection Demonstration Project (BCDDP)] are strikingly similar. All three studies reported that if the biopsy revealed proliferative disease without atypia, the subsequent risk was approximately 1.5x. If the biopsy revealed atypical hyperplasia (AH), the risk was approximately 4.5x. If the patients with AH had a family history of breast cancer, their subsequent risk approached that of patients with in situ carcinoma (approximately 8-10x). In addition to family history, menopausal status seemed to play a role. In patients with AH, the breast cancer risk was much higher in pre- than post menopausal patients. While the classification scheme proposed by Page and co workers is useful in assigning different levels of risk to women with benign breast disease, it has not been universally accepted. Our major short-term goal should be to encourage pathologists to apply these criteria in a reproducible manner in their daily practice.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8007710 TI - Lobular carcinoma in situ (LCIS): pathology and treatment. AB - Lobular carcinoma in situ (LCIS) is not only a relative newcomer among breast lesions, but in its short span of 50 years it has gradually evolved from a rare form of breast cancer to being merely a marker of increased risk. This change has not been without controversy which persists to the present day, although there is now general agreement on the natural history of the disease. The present report represents an update on current thinking about LCIS as well as a review of the limited number of studies dealing with the natural history of the lesion when treated by biopsy alone. Invasive cancer will develop in approximately 20-25% of women with LCIS provided there is sufficient follow-up after biopsy. Precise estimates are not possible since LCIS is an asymptomatic lesion that never makes a mass or reveals itself on mammography. It is found only by biopsy and thus the population being followed is a selected one. Every study has shown that when invasive cancer develops, it is just as likely to appear in the contralateral as in the biopsied breast, and invasive ductal cancers are more common than lobular. Clearly, the small round cells with pale cytoplasm that characterize LCIS do not go on to invasion in the usual patient; rather they serve to identify women who are more likely to develop breast cancer. Such patients represent a clearly defined group at increased risk, and for that reason are ideal candidates for chemoprevention. If tamoxifen or some other agent proves to be effective, the remaining arguments favoring mastectomy for LCIS will finally disappear. PMID- 8007711 TI - Diagnostic criteria and cancer risk of proliferative breast lesions. AB - Breast cancer risk assessment in women following a benign breast biopsy is a promising area with regard to intermediate endpoint determination, and has been particularly fostered by the consensus agreement concerning the risk attributed to specific diagnoses [1]. Several recent studies have largely verified this approach [2-4], and a recent report demonstrates general agreement among most expert pathologists regarding diagnostic criteria for these lesions [5]. However, in a limited number of cases, determining exact levels of risk for individual patients has been problematic as a result of a failure by pathologists to achieve consensus on diagnostic criteria for these same lesions. This situation has arisen primarily because it is much more tenable to disagree over subjective diagnostic criteria, than it is to argue with robustly supported epidemiological data. Without agreement on reproducible diagnostic criteria, widely promulgated consensus risk estimates for these specific histologic entities are no longer applicable. In addition, those individuals who choose different diagnostic criteria for proliferative breast lesions fail to realize that the terminology, epidemiological risk estimates, and diagnostic criteria used by Dupont and Page are inexorably linked. Since the publication of the consensus statement [1], those using the terms of "atypical ductal hyperplasia" and "atypical lobular hyperplasia" have by default accepted the diagnostic criteria of Dupont and Page. Therefore, surgical pathologists who desire to make use of the consensus risk estimates must familiarize themselves with diagnostic criteria for the various histologic entities that comprise proliferative disease of the breast as defined by Dupont and Page [6].(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8007712 TI - The introduction of activated oncogenes to mammary cells in vivo using retroviral vectors: a new model for the chemoprevention of premalignant and malignant lesions of the breast. AB - Breast cancer is an important disease site for chemopreventive intervention. The current in vivo rodent models for breast cancer do not adequately approximate the human disease. Thus, we developed a new series of models based on the direct introduction of activated oncogenes into in situ mammary ductal cells in the rat. So far we have introduced both activated ras and neu into the mammary parenchyma of the rat. Both oncogenes cause the development of mammary carcinomas without any additional exogenous intervention. The activated neu gene is, however, 200 times more penetrant than the activated ras gene. The carcinomas induced by both genes are more aggressive than those induced by chemical carcinogens. They are more often transplantable, locally invasive, and metastatic. Tumors arising from the introduction of the neu oncogene have a greater histopathological resemblance to human breast cancers than those associated with ras insertion. For example, within a week post-introduction of neu, lesions resembling ductal carcinomas in situ are observed in the rat mammary gland. These do not occur following ras introduction or exposure to chemical carcinogens. These models are helping to better define the cellular and molecular events associated with the multistage progression of breast cancer. They are also being used to develop models to evaluate chemopreventive approaches for breast cancer. For example, in the area of cancer prevention we have shown that hormonal intervention is more effective in preventing neu-initiated breast cancers than ras-initiated breast cancers. We have also shown that the chemopreventive monoterpene, d-limonene, can prevent ras induced mammary tumors in this model.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8007714 TI - Fine needle aspiration of the breast for diagnosis of preinvasive neoplasia. AB - Fine needle aspiration (FNA) of the breast is a well-tolerated procedure used to evaluate palpable breast masses, has a reported mean specificity of 99%, and a reported sensitivity of 70-99%. The false positive rate varies from 0-0.4% in most larger series, with a reported false negative rate ranging from 0.7-22%; however, higher false negative rates have been reported in tumors under 2 cm in diameter. The FNA technique uses a fine, 20 gauge or less, needle and is not associated with a significant risk of tumor growing out the needle tract. FNA cytology is not effectively used if a breast mass cannot be palpated or distinguished from fibrous tissue within the breast. The procedure can be applied to nonpalpable masses detected by mammography by employing stereotactic techniques. The cytologic samples obtained from FNA can be used to distinguish atypical ductal hyperplasia from in situ or invasive ductal carcinoma; however, cytologic criteria to effectively distinguish ductal carcinoma in situ (DCIS) from invasive adenocarcinoma are not definitive in many cases, and are dependent on variables related to the type of intraductal tumor, the size and character of the cell groups, and the presence of single or disaggregated tumor cells. Employing current cytologic criteria, lobular carcinoma in situ (LCIS) may be distinguished from invasive lobular carcinoma in some cases; however, the individual LCIS cells are not morphologically distinct from lobular carcinoma cells. Atypical lobular hyperplasia has cellular features essentially the same as those seen in LCIS. Needle biopsy (NB) employs larger needles of 14-16 gauge.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8007713 TI - Cancer chemoprevention with the adrenocortical steroid dehydroepiandrosterone and structural analogs. AB - Dehydroepiandrosterone (DHEA) is an adrenocortical steroid that produces broad spectrum cancer chemopreventive action in mice and rats. In the mouse two-stage skin tumorigenesis model, DHEA treatment inhibits tumor initiation, as well as tumor promoter-induced epidermal hyperplasia and promotion of papillomas. There is considerable evidence that DHEA exerts its anti-proliferative and tumor preventive action through the inhibition of glucose-6-phosphate dehydrogenase and the pentose phosphate pathway, which generate NADPH (required for mixed-function oxidase activation of chemical carcinogens, as well as for deoxyribonucleotide synthesis) and ribose 5-phosphate (also required for deoxyribonucleotide synthesis). Long-term DHEA treatment of mice also reduces weight gain (apparently by enhancing thermogenesis), and appears to produce many of the beneficial effects of food restriction, which have been shown to inhibit the development of many age-associated diseases, including cancer. Using the mouse two-stage skin tumorigenesis model, we found that adrenalectomy completely reverses the anti hyperplastic and antitumor-promoting effects of food restriction. It is not unlikely that food restriction stimulates enhanced levels of adrenocortical steroids, such as the anti-inflammatory glucocorticoids and DHEA, which in turn mediate the tumor-inhibitory effect of underfeeding. PMID- 8007715 TI - Diagnostic cytology of small mammary carcinomas. AB - This brief article summarizes the historical background of the thin needle aspiration technique as it applies to diseases of the breast. The technique and the achievements of this method in the diagnosis of small breast cancers are reported. A brief note on the value of nipple secretions in the diagnosis of carcinoma of the mammary ducts is appended. PMID- 8007716 TI - Breast imaging and breast cancer prevention. AB - Earlier detection of breast cancer through periodic screening is the only currently available intervention likely to reduce breast cancer-related mortality in the near term; prevention would be preferable. The alteration of proliferative changes and the assessment of intermediate endpoints may establish some interventions as more likely than others to interrupt the progression to lethal cancer. However, since not all breast cancers are fatal, the endpoint that will ultimately be accepted as proof of prevention success will be a reduction in breast cancer mortality. Methods of detection and monitoring must be carefully tailored so that the influences of the detection techniques do not alter the prevention results. PMID- 8007718 TI - Code for nurses: a guide for nurses' interaction with nurses. PMID- 8007717 TI - Quantitative microscopical and confocal laser scanning microscopy for intermediate endpoint biomarkers in breast cancer: potential and reproducibility. AB - Diagnostic quantitative pathological (QP) determinations are increasingly used in our hospital. The number of requests for QP for reference materials is rising rapidly. This is understandable; quantitative assessments have a strong prognostic value and can be very reproducible, depending on the care taken with a number of factors including cell and tissue processing, application of the appropriate stains, and the measurement protocol used. As to the latter, systematic random sampling gives the best intra- and interobserver agreement (with correlation coefficients between observers for certain features > or = 0.94). Flow cytometric determinations are often regarded as more reproducible than interactive morphometry due to the high speed of the assessments, the large number of objects measured per specimen, and the lack of observer interaction. Indeed, flow cytometrically assessed DNA ploidy is very reproducible, even though the % S-phase fraction is much more variable. Unlike image cytometry (ICM), visual inspection of cells is not easily accomplished with flow cytometry (FCM). With ICM, the fully automated measurement of DNA in thousands of cells is possible in 3-5 minutes, with a very low coefficient of variation (< or = 2% for the diploid and tetraploid peak of liver cell nuclei). ICM also allows measurement of texture features. However, quantitative immunohisto/cytochemical determinations may not always be as reproducible as sometimes believed. Recently, we found large variations in the measurements, made by a commercially available image processing instrument, of the estrogen and progesterone receptors, Ki-67, cathepsin D, and neu protein overexpression in breast cancer.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8007719 TI - Role of nurse coordinator of pulmonary rehabilitation. PMID- 8007720 TI - Use of restraints in the elderly in long term care facilities. PMID- 8007721 TI - Memory disorders clinic. PMID- 8007722 TI - Educational needs of families of critically ill patients. PMID- 8007723 TI - Volunteer Interfaith Caregivers of Kentuckiana (VICK)--a timely concept. PMID- 8007725 TI - Reclaiming an orphan genre: the first-person narrative of illness. PMID- 8007724 TI - Neighborhood Nurse Project. PMID- 8007726 TI - A call for narrative: the patient's story and anesthesia training. AB - Narrative plays a key role in medical education and knowledge, via the case history, the case presentation, or even the patient's chart. Hospitalization for elective surgery provides the structure for a discrete story in a person's life. The details make the story unique for each patient. By analyzing themes and content of narratives obtained from patients and medical trainees, the reader gains insight into the realms of patients' and residents' lives. We believe that even anesthesiologists, who work at the procedure-oriented end of the spectrum of patient care, can benefit from a narrative approach to understanding the patient's perspective. An unanticipated reward of the study is the therapeutic benefit that some of the patients express in their narratives. Patients write that they hope future patients will benefit ("Use this information to the betterment of anyone in need & etc" [patient 15]) or physicians and nurses will improve their interactive skills (patient 09). Perhaps physicians may share the rewards of narrative creation that patient 10 expresses when he triumphantly exclaims, "EUREKA!!! ... I hope you learn something from it (as I have from remembering it)." Patients can provide medical personnel not only with signs and symptoms, but also with insight into the human aspects of the medical process. Reading or writing narratives about such processes may enhance physicians' understanding of their patients' experiences. PMID- 8007727 TI - Lighting the way: the temporal dimension of narrative in psychotherapy. PMID- 8007728 TI - Reconfiguring the hysterical body: midwifery stories meet the Zavanelli maneuver. PMID- 8007729 TI - Covenants of work and grace: themes of recovery and redemption in polio narratives. PMID- 8007730 TI - The diminishing world of the aging person: the art of Elizabeth Layton. PMID- 8007731 TI - The bioethicist as author: the medical ethics case as rhetorical device. PMID- 8007732 TI - "My story is broken; can you help me fix it?" Medical ethics and the joint construction of narrative. PMID- 8007733 TI - Making hospice work: collaborative storytelling in family-care conferences. PMID- 8007734 TI - Women's health provisions in the Clinton health care reform plan. PMID- 8007735 TI - Disciplinary proceedings before the board of nursing. PMID- 8007736 TI - Nurses in advanced practice moving into 1994 with LD 1185. PMID- 8007737 TI - Guest column on health care reform. PMID- 8007738 TI - ACAT inhibitors as antiatherosclerotic agents: compounds and mechanisms. AB - Atherosclerosis is a major death cause in western industrialized countries. A diagnosing system, medical prevention, and treatment of atherosclerosis is not sufficient so far. A direct acting antiatherosclerotic agent is eagerly waited. ACAT inhibitor approach could provide such an agent. In the formation of atherosclerosis, cholesteryl esters, which are the lipids which accumulate in atheromatous plaques by an aid of macrophages and smooth muscle cells, forming foam cells, may play an important role. ACAT enzyme is responsible for the acylation of cholesterol to cholesteryl esters, a transformation which can be essential in not only cholesteryl esters accumulation at arterial walls but also the absorption of cholesterol in the intestine and the excretion of cholesterol in the liver. From these points, ACAT inhibitors might work against atherosclerosis in three different ways: first, cholesteryl ester accumulation inhibition at arterial walls could be a direct antiatherosclerotic effect; second, cholesterol absorption inhibition at the intestine; and third, cholesterol excretion acceleration at the liver, while the later two effects would result in a reduction of blood cholesterol level--a major risk factor of atherosclerosis. Taking account of this discussion, the ACAT inhibitors would be potent antiatherosclerotic agents. Medicinal research has been contributing full strength to produce an ultimate compound. These efforts should provide a drug which will be useful to patients. PMID- 8007739 TI - Synthesis of carbohydrate-containing surface antigens of mycobacteria. PMID- 8007740 TI - Medicinal applications of cyclodextrins. AB - Some cyclodextrins are produced industrially, and available in pharmaceutical quality, at reasonable prices. Their medicinal use means mainly--but not exclusively--the complexation of problematic drugs (poorly soluble, unstable, irritating, difficult to formulate substances). The CD complexation generally results in improved wettability, dissolution, and solubility; improved stability; reduced side effects; or in mildering of other undesired properties (e.g., bitter tastes, bad smells). CDs can be used advantageously practically in any drug forms: oral, rectal, pulmonary, external, ocular, etc. formulations. In oral solid and liquid formulations the chemical and physical stability and bioavailability, but particularly the role of absorption is improved. With appropriate highly soluble chemically modified CDs aqueous parenteral formulations can be prepared from poorly soluble drugs. Using CDs the transdermal penetration or nasal absorption of such drugs becomes possible, which earlier could not be administered through these ways. The direct therapeutic effects of CDs (or their derivatives) are demonstrated in several examples as well as the use of beta CD as vehicle in tabletting. PMID- 8007741 TI - Enzymatic method for quantitating lactate dehydrogenase isoenzyme composition in cardiac tissue: utilization of the method to characterize newborn and adult rat heart. AB - Lactate dehydrogenase (LDH) is an enzyme of special interest due to its key position in anaerobic metabolic pathways. Work on the structure and developmental expression of LDH led to formulation of the isoenzyme concept as well as elucidation of the biological significance of isoenzymes. Tissue isoenzyme compositional changes are mediated by changes in pattern of gene expression for two primary LDH gene loci in vertebrates. Developmental shifts in LDH gene expression prompted other experimental interventions to alter gene expression schedule and enzyme synthesis in order to pinpoint underlying genetic and molecular control mechanisms. LDH isoenzymes in tissues can be separated by electrophoresis and then quantitated by scanning densitometry; however, these methods require specialized instruments. Enzyme specific activity can be assessed spectrophotometrically, but enzymatic activity determination alone does not provide quantitation of LDH isoenzyme(s). The present work was conducted to establish a spectrophotometric enzyme assay procedure based on differential substrate inhibition to quantitate tissue LDH isoenzymes. The procedure was then used to assess developmentally related alterations in LDH isoenzymes in cardiac tissue of newborn and young adult rats. Results show that heart tissue in 5-day old newborn rats possesses approximately equal proportions of muscle type (anaerobic) and cardiac type (aerobic) LDH isoforms. As normal development transpires, heart tissue LDH isoenzyme proportion shifts with substantial decrease in anaerobic form which is accompanied by marked augmentation in aerobic form. PMID- 8007742 TI - A new method for the determination of the bioavailability of thyroid hormone preparations. AB - Levothyroxine and levotriiodothyronine are vital hormones that are produced and stored in the thyroid gland. Due to endogenic hormone production and regulation, it is impossible to determine the bioavailability of exogenic hormone using conventional trial designs since exogenic hormone cannot be distinguished from endogenic hormone in serum unless radiolabelled. Bioavailability, however, is an essential quality attribute of thyroid hormone preparations. A new trial design was developed that allows the bioavailability of thyroid hormone preparations to be determined without the use of radiolabelled substances. The trial subjects were volunteers (athyreotic patients) who, after thyroidectomy and postoperative radioiodine therapy, do not produce endogenic thyroid hormone and have to be supplied with exogenic levothyroxine on a permanent basis (replacement therapy). An oral solution of levothyroxine was used as a reference. Such a solution can be prepared with the same biopharmaceutical quality on a reproducible basis and is suitable for comparing preparations with one another that are used in different trials with the same design. The orally given reference solution is well tolerated and can therefore be administered over the required periods of time (e.g., 3 x 4 weeks). In a randomized, 3-way Latin-square design, the volunteers were given either L-Thyroxin Henning, another tablet preparation, or the reference solution, each for 28 days running during each period. On days 26, 27 and 28 of each period, the serum concentrations of levothyroxine and levotriiodothyroine were determined in order to verify the steady state.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8007743 TI - Brain interleukin-1 beta in Alzheimer's disease and vascular dementia. AB - Recent investigations indicate that a neuroimmune reaction, associated with inflammatory mechanisms, can contribute in Alzheimer's disease (AD) to cell damage and neurodegeneration. Activation of microglial cells, expression of immunohistochemical markers of brain immune function, the presence of complement proteins in brain tissue and changes in cytokine production have been reported in AD. We have studied the concentration of interleukin-1 beta (IL-1 beta) in different regions of the central nervous system (CNS) in post-mortem samples from patients with AD or vascular dementia (VD) and in age-matched control subjects (CS). IL-1 beta levels were significantly higher in AD than in VD or CS in the frontal cortex, parietal cortex, temporal cortex, hypothalamus, thalamus and hippocampus. The highest increases in IL-1 beta levels were observed in the frontal cortex (CS = 0.75 +/- 0.045; AD = 2.47 +/- 0.12, p < 0.001; VD = 1.52 +/- 0.078 pg/mg, p < 0.001) and hippocampus (CS = 0.71 +/- 0.042; AD = 2.63 +/- 0.19, p < 0.001; VD = 1.21 +/- 0.23 pg/mg, p < 0.01). No significant changes were detected in the occipital cortex and cerebellum in either AD or VD. These results clearly demonstrate that demented patients show a generalized increment of IL-1 beta production in the CNS, with maximum response in those brain regions where AD neuropathology is most prominent. This overall increase in cytokine production might represent an early event in the activation of a neuroimmune cascade leading to cell death and neurodegeneration in brain regions where a primary cause (e.g., genetic, toxic, vascular) facilitates the induction of resting microglia for firing brain immune function. PMID- 8007744 TI - Red blood cell sodium-lithium countertransport in patients with essential and renal hypertension. AB - The erythrocyte Na+/Li(+)-countertransport activity was studied in patients with essential hypertension (n = 59), chronic glomerulonephritis (n = 30), chronic pyelonephritis (n = 26), renovascular hypertension (n = 35) and pheochromocytoma (n = 3). The erythrocyte Na+/Li(+)-countertransport (SLC) activity was on average higher (p < 0.02) in the patients with essential hypertension as compared to those with secondary hypertension, although a clear distinction between both groups was not possible. After surgical treatment of the patients with atherosclerotic renal artery stenosis, fibromuscular dysplasia or pheochromocytoma, no change in erythrocyte SLC activity was observed. However, blood pressure was significantly reduced. PMID- 8007745 TI - Uptake and killing of Candida by human peritoneal macrophages and amphotericin B. AB - The effects of amphotericin B at subinhibitory and inhibitory concentrations on ingestion and intracellular killing of C. albicans ATCC 10,231 and C. tropicalis ATCC 13,803 by human peritoneal macrophages in vitro was investigated. Peritoneal macrophages were harvested from overnight peritoneal dialysate of 26 patients undergoing regular continuous ambulatory peritoneal dialysis (CAPD) using a new simple isolation technique. Macrophages were suspended with Candida (1:2-3) together with pooled human serum and with or without amphotericin B at various concentrations. Vital staining with acridine orange at a very low concentration using the metachromatic property of the dye allowed simultaneous assessment of ingestion and intracellular viability of the yeasts. Counts of Candida in 100 macrophages were performed at 1, 2, 3, 4, 6 and 24 h under a fluorescence microscope at 1000x and the ratios of living to dead intracellular Candida were calculated. Amphotericin B was added at concentrations of 0.1, 1 and 10 times the MIC. Ingestion was rapid and complete, while intracellular killing ranged from 4 69% for C. albicans and from 9-48% for C. tropicalis. Amphotericin B at 1 MIC enhanced the killing of C. tropicalis (factor 1.32) but reduced killing of C. albicans (factor 0.6) after 6 h. PMID- 8007746 TI - Block effects of IHC-72 on calcium current in single guinea pig cardiac myocytes. AB - Block of the calcium current by IHC-72 in single ventricular myocytes isolated from guinea pig was studied by using the whole-cell patch clamp technique. IHC-72 in micromolar concentrations depressed the calcium current in a concentration dependent manner, with an IC50 of 0.06 +/- 0.02 mcmol/l. After application of IHC 72 the peak calcium current began to decrease within 1 min and reached a steady state within 10 min. The current-voltage relationship for the calcium current peak was not changed by IHC-72, but the amplitude was significantly suppressed. Although IHC-72 did not alter the time course of inactivation of the calcium current, it shifted its steady state. PMID- 8007747 TI - Sex difference in the feeding responses of non-deprived rats to the 5-HT1A agonists 8-OH-DPAT and gepirone. AB - The aim of this study was to determine whether there was any difference in the feeding responses of male and female rats to the 5-HT1A agonists 8-hydroxy-2(di-n propylamino)tetralin (8-OH-DPAT) and gepirone. 8-OH-DPAT (62.5 and 500 mcg/kg, s.c.) and gepirone (1, 2 and 4 mg/kg, s.c.) significantly increased the amount of food consumed by non-deprived male rats (p < 0.01 in each case) over a 2 h period. Similar doses of 8-OH-DPAT and gepirone had no effects on food intake in non-deprived female rats. However, a higher dose of gepirone (i.e., 8 mg/kg, s.c.) significantly increased feeding (p < 0.01) in non-deprived female rats. These results thus show a clear-cut sex difference in the sensitivity of non deprived rats to the hyperphagic effects of 5-HT1A agonists. PMID- 8007749 TI - "All that pertains to medicine": protomedici and protomedicati in early modern Italy. PMID- 8007748 TI - Divalent cations in hypertension with implications to heart disease: calcium, cadmium interactions. AB - Heart disease still pervades all socioeconomic classes within the United States. Understanding the effects of environmentally-related pathogenesis (e.g., heavy metal accumulation) may aid in developing novel treatments for the prevention of heart dysfunction. The aim of this report was to use experimental investigation in an attempt to expand upon the multivariate importance of divalent cation interactions in the development of heart disease. Calcium and cadmium levels were measured by flame atomic absorption spectrophotometry in various tissues derived from two types of hypertensive rabbit models. Both models of hypertension developed mean arterial pressures of at least 50 mm mercury greater than those of controls over a 5 week period. Interrelationships between calcium and cadmium levels were found to exist for both hypertensive groups in the left ventricle, aorta, and renal medulla. The renal cortex showed no such interrelationship for the renal hypertensive group. Multiple interrelationships between calcium and cadmium levels and hypertrophy were also observed. These studies related the importance of endogenous or exogenous (viz, environmental) factors governing cadmium and calcium accumulation in hypertensive rabbits. The resulting relationships between divalent cations and hypertrophy were presented to draw attention to areas which remain unexplored with perspective to cardiovascular disease. PMID- 8007750 TI - Edmund Gosse and the "new and fantastic cure" for breast cancer. PMID- 8007751 TI - Medical women at war, 1914-1918. PMID- 8007752 TI - Osteotomy as an indicator of antiseptic surgical practice. PMID- 8007753 TI - Brown-Sequard's spinal epilepsy. PMID- 8007754 TI - A medieval sculpture of leprosy in the Cistercian Abbaye de Cadouin. PMID- 8007755 TI - Methamphetamine (METH) causes reactive gliosis in vitro: attenuation by the ADP ribosylation (ADPR) inhibitor, benzamide. AB - We examined the effects of methamphetamine (METH) in an in vitro model of rat fetal mesencephalic cells. METH causes loss of dopamine (DA) cells and neuronal process degeneration. In addition, the drug causes an increase in reactive gliosis as shown by the number of cells that stain for and by the intensity of staining with a glial fibrillary acidic protein (GFAP) antibody. Co-incubation of METH-treated cells with benzamide, which is a known inhibitor of ADP-ribosylation (ADPR), attenuated METH effects on both DA and glial cells. However, the effects of benzamide were somewhat more prominent on the glial cells. These results suggest that ADP-ribosylation may play a very important role in the development of reactive gliosis after the administration of neurotoxic agents. PMID- 8007756 TI - Enhanced susceptibility of erythrocytes deficient in glucose-6-phosphate dehydrogenase to alloxan/glutathione-induced decrease in red cell deformability. AB - It has been hypothesized that enhanced oxidant sensitivity of glucose-6-phosphate dehydrogenase (G6PD) deficient red cells(RBCs) is the underlying mechanism for drug- or chemical-induced hemolytic crises in G6PD-deficiency. To further test this hypothesis, we used an alloxan-glutathione system to mimic oxidative stress and see how oxidative damage might affect RBC deformability. RBC deformability, a major determinant of RBC survival in vivo, was monitored by a laser viscodiffractometer. Under our experimental conditions, GSH alone had very little effect on the deformability of either normal or G6PD-deficient RBCs. In contrast, alloxan alone induced a small but significant decrease in the deformability of either normal or G6PD-deficient RBCs. Interestingly, alloxan and GSH together induced a further decrease in the deformability of either normal or G6PD deficient RBCs. The decrease in deformability in G6PD-deficient RBCs was much more profound than in normal RBCs. In addition, an alloxan-vitamin C system produced a similar deleterious effect on RBC deformability as that produced by the alloxan-GSH system. Appreciable amount of hydroxyl radicals was generated by both alloxan-GSH and alloxan-vitamin C systems as evidenced by the production of hydroxylated products of salicylate which was used as a radical trap. Moreover, salicylate could ameliorate the deleterious effect of the alloxan system on the deformability of RBCs. Taken together, our results demonstrated that G6PD deficient RBCs were particularly susceptible to oxidant-induced damage leading to a dramatic decrease in their deformability and thus provided strong support for the hypothesis that enhanced oxidant sensitivity of G6PD-deficient RBCs is the underlying mechanism for accelerated destruction of these RBCs in vivo. PMID- 8007757 TI - CGS 15943, an adenosine A2 receptor antagonist, reduces cerebral ischemic injury in the Mongolian gerbil. AB - The adenosine A2 receptor antagonist CGS 15943 (0.1 mg/kg, i.p.) was tested for cerebroprotective activity in a gerbil stroke model. CGS 15943 markedly reduced stroke injury assessed by locomotor activity monitoring and by histopathological measurement of hippocampal CA1 pyramidal cell injury. It is proposed that a previously demonstrated reduction in the ischemia/reperfusion-evoked release of excitotoxic amino acids following CGS 15943 administration could account for its cerebroprotective actions. PMID- 8007758 TI - Uptake inhibitors increase extracellular serotonin concentration measured by brain microdialysis. AB - The physiological role of the serotonin transporter on serotonin neuronal membranes apparently is to inactivate serotonin that has been released into the synaptic cleft. Drugs that inhibit the uptake of serotonin increase the amount of serotonin in the synaptic cleft and enhance serotonergic neurotransmission. As an adaptive response to the increased amount of serotonin in the synaptic cleft, serotonin neurons decrease their firing and release of serotonin to limit the magnitude of the increase in extracellular serotonin concentration. The increase in extracellular serotonin in rat brain caused by inhibitors of the serotonin uptake carrier has been characterized by brain microdialysis coupled to liquid chromatography with electrochemical detection. These drugs cause rapid accumulation of extracellular serotonin in several brain regions, although the increase in frontal cortex may be smaller than in other nerve terminal regions or in the cell body-containing raphe region. PMID- 8007759 TI - Nephrotoxicity of low doses of tobramycin in rats: effect of the time of administration. AB - The circadian and the circannual variations of the nephrotoxicity of tobramycin were studied in female Sprague-Dawley rats. Animals were maintained on a light dark period of 14/10 hrs (light on: 06h00 to 20h00). They were injected once daily for 4 and 10 days with saline or tobramycin at a dose of 40 mg/kg/day i.p. at either 08h00, 14h00, 20h00 and 02h00, in April 1991, July 91, October 91, January 92. In April 91, tobramycin injected at 14h00 during 10 days induced a significant increase of [3H]-thymidine incorporation into DNA of renal cortex as compared to other groups (p < 0.01): toxicity was highest at 14h00 and lowest at 02h00. No temporal change was observed in the renal cortical accumulation of tobramycin, and in serum creatinine after the 4 or 10 days of treatment. In experiments done in April, July and October 1991 and in January 1992, no circannual variation was found in tobramycin cortical levels but peaks of toxicity were observed at 02h00 in April and October 1991 and at 14h00 in July 1991 and January 1992. There was no linear correlation between the toxicity and the tobramycin accumulation in the renal cortex (r = 0.21). The data suggest that the circadian changes in tobramycin toxicity are due to temporal changes in the susceptibility of renal cells to tobramycin. PMID- 8007760 TI - Influence of an alternative reinforcer on human cocaine self-administration. AB - Identifying factors that modulate cocaine self-administration is fundamental to the development of effective strategies to treat and prevent cocaine abuse. In the present study, the influence of an alternative reinforcer on the probability of cocaine use was examined in four adult humans under controlled laboratory conditions. During eleven test sessions, subjects chose between cocaine hydrochloride vs. placebo or between cocaine vs. varying amounts of money (0 $2.00/choice). Subjects made a maximum of 10 exclusive choices per session. Cocaine and placebo were administered intranasally in 10 mg unit doses under double-blind conditions. Subjects exclusively chose cocaine over placebo demonstrating that the drug functioned as a reinforcer. During sessions comparing cocaine vs. money, choice of cocaine decreased as the amount of money available in the monetary option increased, with all subjects exclusively choosing the monetary option in the $2.00 per choice condition. These results systematically replicate and extend to humans prior findings in laboratory animals demonstrating that the availability of alternative, nondrug reinforcers can significantly decrease cocaine use. PMID- 8007761 TI - [3H]GBR 12935 binding to human platelet membranes is sensitive to piperazine derivatives but not to dopamine uptake inhibitors. AB - It remains controversial whether blood platelet can be used as a peripheral model for the central presynaptic dopaminergic neurons. We investigated the existence of dopamine transport complex in human blood platelet membranes using the selective dopamine uptake inhibitor [3H]GBR 12935 as a radioligand. In contrast to [3H]GBR 12935 binding to rat striatal dopamine carrier site, the high affinity [3H]GBR 12935 binding to platelet membranes was insensitive to mazindol and other dopamine uptake inhibitors. Piperazine derivatives including GBR 12909 were found to be potent inhibitors of [3H]GBR 12935 binding to platelet membranes. [3H]GBR 12935, piperazine derivative-sensitive binding to platelet membranes was inhibited by increasing sodium concentration. Kinetic experiments revealed that both association and dissociation rates of [3H]GBR 12935 binding were slower to platelet membranes than to striatal membranes. These results indicate that [3H]GBR 12935 binding to platelet membranes is different from the binding of this ligand to the dopamine uptake complex and seems to label a "piperazine acceptor" site which was previously demonstrated in brain and liver membranes. PMID- 8007762 TI - Modulatory action of neurotensin on the pituitary-adrenocortical function in rats: evidence for an acute dose-dependent biphasic effect. AB - Adult female rats were sc injected with 0.6 or 1.2 nmol/100 g body wt of neurotensin (NT); control animals received a sc injection of saline vehicle. The plasma concentrations of ACTH, aldosterone and corticosterone were measured 1, 2 or 4 h after the injection. Our RIA estimates revealed that the lower dose of NT exerted a net stimulatory effect on the rat pituitary-adrenocortical function, that can be ascribed to the well-known NT-evoked enhancement of CRH release. Conversely, the higher dose of NT appeared to have a marked inhibitory effect on both pituitary ACTH release and adrenocortical secretion. The mechanism underlying this last action of NT remains to be elucidated. PMID- 8007763 TI - Localization of a low Mr GTP-binding protein, rap1 protein, in plasma membranes and secretory granule membranes of rat parotid gland. AB - Subcellular fractions were prepared from rat parotid gland by sequential centrifugation, Percoll gradient centrifugation and divalent-cation precipitation, and the localization of a low Mr GTP-binding protein, rap1 protein (rap1p) was analyzed by immunoblotting using a specific antibody. rap1p was found to be located in apical and basolateral plasma membranes, and secretory granule membranes in rat parotid gland. On the other hand, the beta gamma subunits of heterotrimeric Gt protein was localized in plasma membranes but not in granule membranes. PMID- 8007764 TI - Effect of metallothionein I on mitochondrial oxygen consumption. AB - The effect of the stress-induced, cysteine-rich protein, metallothionein I (MT), on oxygen consumption by rat liver mitochondria was studied. Using a Clark-type oxygen electrode we found that electron transport from succinate to oxygen was enhanced by MT whereas ADP-initiated oxygen consumption was inhibited by MT. The MT effect was concentration dependent. No evidence was found for the provision by MT of an alternate pathway to oxygen. PMID- 8007765 TI - Effects of hysterectomy on ovulation and related ovarian functions in regular estrous cycle rats. AB - The number of ovulation was significantly higher in hysterectomized rats with regular estrous cycles than in sham-operated rats at the estrous stage 20-24 days after operations (13.2 +/- 0.33 vs. 11.8 +/- 0.41, P < 0.05). This finding suggests that hysterectomy facilitates the follicular maturation in rats. To examine the mechanism of facilitation on follicular maturation in hysterectomized rats, plasma FSH level, ovarian estradiol-17 beta (E2) and ovarian aromatase activity were measured 20 days after hysterectomy. Hysterectomy had no effect on plasma FSH levels at any of the estrous stages. Ovarian E2 level and aromatase activity (AA) were significantly increased by hysterectomy only at diestrus-2 stage of the estrous cycle (E2; 3.76 +/- 0.49 vs. 1.48 +/- 0.49 ng/g ovarian tissue, P < 0.05, AA; 1.36 +/- 0.15 vs. 0.83 +/- 0.11 pmol/h. mg ovarian tissue, P < 0.05), but ovarian testosterone level was not affected by the operation. These results support the hypothesis that in rats hysterectomy facilitates follicular maturation. This may be due to an increase in ovarian E2 level at the diestrus-2 stage, caused by heightened ovarian aromatase activity. PMID- 8007766 TI - Functional brain MR imaging based on bolus tracking with a fast T2*-sensitized gradient-echo method. AB - Dynamic physiological scanning, based on temporary changes in local field homogeneity during the passage of a contrast agent bolus, has been performed hitherto with echo-planar imaging (EPI) or conventional gradient-recalled techniques (FLASH). Here, it is shown that the T2* sensitivity of conventional FLASH techniques can be improved drastically on a conventional whole body instrument by delaying the gradient-echo until the subsequent TR-period without increasing total imaging time. Examples are given for a full k-space matrix (128 x 256) obtained within 2 s with a TE of 25 ms, resulting in images free of artifacts. The method is applied to bolus tracking through the brain of healthy volunteers during visual stimulation and in the dark. An average increase of regional cerebral blood volume (rCBV) in the visual cortex of 10.9% (n = 9, p = .001) was found. PMID- 8007767 TI - White matter hyperintensities in dementia: does it matter? AB - The aim of the study was to investigate whether the regional distribution of white matter hyperintensities (WMH) observed by magnetic resonance imaging differed between vascular dementia and patients with late onset Alzheimer's disease. Another aim was to investigate the relations between the occurrence and degree of WMH and clinical and laboratory data as well as measures of cognitive decline. White matter hyperintensities were assessed with a low field magnetic resonance imager on 23 subjects with probable Alzheimer's disease, 25 with possible Alzheimer's disease and 31 subjects with vascular dementia. The degree and regional distribution of the WMH (expressed as relative volumes) were calculated and compared in the three groups. The relation between cognitive impairment and the degree of the WMH was also studied. The regional distribution of the WMH differed between the groups with significantly more changes in the posterior part of the brain (p < .0001) as well as in the right hemisphere (p < .0005) in the vascular demented as compared to the patients with Alzheimer's disease. No significant correlations between cognitive impairment and the degree of the WMH were found in any of the groups. The total volume of the WMH as well as the regional distribution of these changes differed significantly between vascular dementia and Alzheimer's disease. White matter hyperintensities seem not to be related to the degree of global cognitive decline in dementia and whether it plays a causative role in the development of dementia symptoms needs to be more thoroughly investigated. PMID- 8007768 TI - Breast tumor imaging with ultra low field MRI. AB - Ultra low field MRI was evaluated for breast tumor imaging. Twenty-seven patients with a known or suspected breast malignancy were imaged preoperatively with a T2 weighted gradient-echo sequence. Additional IR- and gradient-echo sequences were used for measurements of T1 and T2 relaxation times. Seventeen resected specimens were also imaged within four hours after removal. Nineteen of 23 carcinomas detected at mammography were also detected with MRI (sensitivity 83%), and one of four benign cases was evaluated as pathologic (specificity 75%). Most of the tumors had T1 and T2 relaxation times longer than those of normal breast parenchyma. The T1 values of the tumors were significantly different from the T1 values of fat (p = .0002) and breast parenchyma (p = .0151). The tumor T2 values differed significantly from the T2 of breast parenchyma (p = .0223) but not from that of fat (p = .1475). In vitro tumor measurements were similar to the in vivo measurements. Despite these statistically significant findings, the calculated relaxation times were not considered sufficiently reliable for the clinical evaluation of breast tumors. PMID- 8007769 TI - Blood-brain barrier disruption in experimental focal ischemia: comparison between in vivo MRI and immunocytochemistry. AB - The definition of blood-brain barrier (BBB) damage in cerebral ischemia using contrast-enhanced MRI has not been clearly correlated to the spread of edema or other histological measures of barrier disruption. In this study, we used a rabbit model of focal cerebral ischemia to compare GdDTPA-enhanced MRI with spin echo images of brain injury and immunocytochemical detection of BBB damage and vasogenic edema. After 4 h of transient ischemia followed by 6 h of reperfusion, in vivo T2W and T1W images were obtained in a 1.5 T magnet using a 3-inch surface coil. After MRI, the animals were sacrificed and anti-serum protein (IgG) monoclonal antibodies were used to detect regions of increased BBB permeability to serum proteins. Ischemic neuronal damage was confirmed with cresyl-violet histology. T2W scans showed focal regions of increased signal intensity in the ischemic hemisphere (17.0 +/- 4.1%) that primarily involved the cortex and striatum. T1W scans showed corresponding regions of hypointensity but demonstrated, in general, smaller lesion sizes (10.1 +/- 2.9%). GdDTPA-enhanced images showed variable areas of BBB disruption that included regions of intense leakage as well as lesions that only showed subtle enhancement along the periphery of damaged tissue. It appeared that large and more severe lesions corresponded to peripheral enhancement whereas smaller lesions showed central parenchymal enhancement. The extent of MR contrast enhancement did not correlate well with immunocytochemical images of serum protein leakage. Anti-IgG stains demonstrated widespread regions of BBB damage corresponding with areas of damaged neurons that appeared pyknotic on cresyl-violet sections.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8007770 TI - Functional evaluation of normal and ischemic kidney by means of gadolinium-DOTA enhanced TurboFLASH MR imaging: a preliminary comparison with 99Tc-MAG3 dynamic scintigraphy. AB - The functional value of TurboFLASH MR imaging in the assessment of dynamic contrast enhancement and renal perfusion anomalies was evaluated in seven patients, who also underwent renal scintigraphy in baseline conditions. The basal renograms obtained from MAG-3 scintigraphy (mercapto acetyl triglycine, MAG3-S) and from Gd-DOTA-enhanced turboFLASH MRI were compared. After hydration, the protocol used consisted in breath-hold coronal turboFLASH acquisitions after IV bolus of Gd-DOTA (4 s every 20 s during 10 min) for MRI, and IV bolus of 370 MBq of 99mTc-MAG3 followed by 60 frames of 1 s and then 120 frames of 10 s for MAG3 S. Relative renal functions were computed for both methods by calculation of the integral of the uptake phase between the first and the second minute. Renograms exhibited 10 normal and 4 ischemic kidneys. There was a close correlation between the contrast enhancement of MRI and isotopic uptake in normal and ischemic kidneys. Global renograms of MRI correlated with MAG3-S (r = .82, p < .001) with similar curve shape and time to peak. Relative renal function of the right and left kidney were closely correlated in all patients (r = .98, p < .001), although there was a tendency for MR to overestimate MAG3-S evaluation in kidneys with severe basal dysfunction. Enhanced turboFLASH provides noninvasive assessment of renal perfusion in patients with renovascular disease. Accurate renograms are obtained with dynamic-enhanced MRI, but the relative renal function seems to be overestimated in low values of ischemic kidneys, and needs further comparative evaluation. PMID- 8007772 TI - A new nonionic macrocyclic gadolinium(III) chelate as a potential magnetic resonance-imaging contrast agent. AB - A new GdIII complex of a 17-membered macrocycle with three pendant carboxymethyl groups has been synthesized; the ligand has been obtained in a single step from diethylenetriaminepentaacetic dianhydride (pentetic dianhydride) and 1,4 butanediamine (putrescine). An X-ray crystal analysis has shown that the complex is a nonionic metal chelate with a coordinated water molecule. The near-zero electrical conductivity, 1 omega-1 cm2 mol-1, of a 1 mM solution indicated that the metal chelate is essentially undissociated. The NMR T1 relaxivity is 2.5 s-1 mM-1 at a resonance field of 64 MHz, and 3.4 s-1 mM-1 at 250 MHz. This new GdIII complex is a potentially important magnetic resonance imaging contrast agent. PMID- 8007771 TI - Does gadolinium-diethylene triamine pentaacetic acid enhanced MRI of kidney represent tissue concentration of contrast media in the kidney? In vivo and in vitro study. AB - Although Gadolinium-diethylene triamine pentaacetic acid (Gd-DTPA) has been used as a contrast material in magnetic resonance imaging (MRI), it is known that contrast enhancement effect is not uniform if the concentration of Gd-DTPA increases beyond some levels. In this study, to evaluate the proper pulse sequences for dynamic MRI in the human kidney, the concentration of Gd-DTPA was quantitatively measured by inductively coupled plasma (ICP) emission spectrometry in human biological samples after administration of Gd-DTPA. The signal intensity of MRI in the solutions of several concentrations of Gd-DTPA was measured. The results were that in using a low magnetic field apparatus, signal intensity linearly correlated with the concentration of Gd-DTPA between 0 and 2.0 mumol/g under saturation recovery sequences (flip angle = 60 degrees or 90 degrees). Using a high magnetic field apparatus, signal intensity linearly correlated with the concentration of Gd-DTPA between 0 and 2.0 or 3.0 mumol/g under spin-echo or gradient-echo sequences. Gd-DTPA concentration of the renal cortex ranged from 0.132 to 0.152 mumol/g tissue at 5 min after IV injection of Gd-DTPA 0.05 mmol/kg body weight in six patients with adrenal tumor or renal cell cancer, and one patient with both urinary bladder cancer and prostatic cancer. Six of the patients showed normal renal function and the other had renal insufficiency (GFR = 25 ml/min/1.48 m2).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8007773 TI - Biodistribution of an ultrasmall superparamagnetic iron oxide colloid, BMS 180549, by different routes of administration. AB - The ultrasmall superparamagnetic iron oxide colloid BMS 180549 can be found lymph nodes by either subcutaneous (SC) or intravenous (IV) injection. With an SC injection in the front extremities, the axillary and brachial nodes attain the highest accumulations of the agent. With an SC injection in the rear extremities, the popliteal, iliac, and axillary nodes attain highest accumulations of the agent. With IV injection of the agent, the iliac, mediastinal and mesenteric nodes attain highest accumulations of the agent. Though the spleen is not involved with the drainage of the interstitial space near the site of SC injections, the mobility of BMS 180549 from such injection sites increases splenic relaxation rates. Based on a knowledge of the lymphatic system, a route of administration of BMS 180549 can be chosen to maximize the delivery of the agent to specific lymph nodes. PMID- 8007774 TI - A method for myelin fiber orientation mapping using diffusion-weighted MR images. AB - In the past, the anisotropic diffusion of water molecules in white matter in the brain has been correlated to the basic symmetry of the myelin fibers: water diffuses more readily along the fiber direction than perpendicular to it. As a consequence, diffusion sensitized magnetic resonance imaging can be expected to be useful for studying the fiber orientation. In this work, we present a method for exploiting this type of information to map the fiber orientations in the image plane. It makes use of three diffusion-weighted images with sensitizing gradients along x, y and u, an axis at 45 degrees with respect to x and y. The orientation information contained in these images is summarized in a single image representing the angle between the fiber direction and a fixed axis, making use of a cyclic color scale. The method is evaluated using computer simulations for a variety of diffusion weighting strengths and signal-to-noise ratios, tested on a phantom and illustrated on an in vivo example. An extension to the determination of the fiber orientation in three dimensions is also described. PMID- 8007775 TI - Correction of motional artifacts in diffusion-weighted MR images using navigator echoes. AB - Patient motion can seriously degrade the quality of diffusion-weighted MR images obtained using standard 2DFT imaging procedures. The main source of error arises from an MR signal phase-shift error which is proportional to the magnitude of the motion. A modified pulse sequence is proposed which uses the phase information from an additional spin echo to correct for patient motion. Application of this technique is demonstrated for a human brain study, which greatly improves the quantification of diffusion values from regions of brain tissue. PMID- 8007776 TI - Preliminary results of a modified surface rendering technique in the display of magnetic resonance angiography images. AB - Maximum intensity projections are the currently accepted method of displaying Magnetic resonance angiography (MRA) data. In this study, we introduce a modified surface rendering method for displaying this same MRA data. The system we have developed is designed to reconstruct three-dimensional (3D) images of vasculature using standard magnetic resonance images. A workstation was used for post processing that is readily available and inexpensive. Software was written to process the original images and control the commercially available surface rendering algorithm while performing the reconstruction. The standard surface rendering technique was modified by including several velocities of blood flow in the reconstruction. These velocities were assigned varying degrees of translucency, which allow flow information to be included in the reconstructed images. Six subjects were examined using this technique and the images were compared with those from other imaging modalities. This surface rendering method has been shown to produce clearer and more comprehensible images of complex vasculature, both for radiologists, and for physicians of other disciplines. Its success is based on improvements in computing techniques and in acquisition of vascular MR images. The method shows great potential, and with future clinical trials, the true uses of this method will be discovered or confirmed. PMID- 8007777 TI - In vitro NMR micro imaging of the spinal cord of chronic relapsing EAE rats. AB - Chronic relapsing experimental allergic encephalomyelitis (Cr-EAE) was induced in Lewis rats with an emulsion of guinea pig spinal cord tissue in complete Freund's adjuvant enriched with Mycobacterium tuberculosis H37 RA. The sensitized rats developed Cr-EAE showing two to three relapses during the first 40 days. In vitro transverse T2-weighted spin echo images of the spinal cord of Cr-EAE rats, sacrificed at the clinical height (hind leg paralysis and urinary incontinence) of the third bout and their controls, were compared with the corresponding histopathology. Lesions extended over the entire spinal cord, however, the larger lesions were predominantly present in the cervical and upper thoracic regions. In the white matter only areas of demyelination and large perivascular demyelination were discernable on the MR images. Size and shape of these lesions correlated well with the morphological characteristics revealed by histopathology. Plaques in the ventrolateral funiculus were generally located peripherally, while plaques in the dorsal funiculus were mainly present in the medial part. The NMR images, however, could not distinguish between demyelination, remyelination, inflammation, and oedema. Also lesions in the gray matter could not be distinguished with MR imaging techniques. However, if lesions were localized at the interface of the gray and white matter the boundary between the gray and white matter was less well defined. PMID- 8007778 TI - Solid state and microscopy NMR study of the chemical constituents of Afzelia cuanzensis seeds. AB - Multi-echo, chemical shift selective, and 3D NMR imaging at microscopy resolution, and CP/MAS 13C NMR spectroscopy have been applied to the chemistry study of oil in oil-rich seeds of Afzelia cuanzensis, a tropical plant belonging to the Leguminosae taxum Caesalpinoideae or Caesalpinaceae. PMID- 8007779 TI - Quantification of liver fat using magnetic resonance spectroscopy. AB - Localized proton MR spectroscopy using stimulated echoes was used to quantify the liver fat concentration in patients with various degrees of fatty liver due to alcohol abuse. Ten patients underwent a liver biopsy followed by chemical triglyceride estimation of the fatty content. A statistically significant correlation was found between the fat concentration measured in the liver biopsies, and the concentration calculated from the spectroscopic experiments (r = 0.9, p < .001). Quantitative assessment of liver fat concentrations using localized spectroscopy is superior to methods based on differences in relaxation times, and can be used to estimate the fat concentration over the full range of fat content in contrast to the spectroscopic imaging methods. Localized spectroscopy may replace liver biopsy in the diagnosis of diffuse fatty infiltrations, and can be used for follow-up, due to its noninvasive nature. PMID- 8007780 TI - Drug monitoring of 5-fluorouracil: in vivo 19F NMR study during 5-FU chemotherapy in patients with metastases of colorectal adenocarcinoma. AB - The metabolism of 5-fluorouracil (5-FU) is complex and the reason for the low response rate of tumor patients to 5-FU is currently unknown. The aim of this study was to evaluate whether spectral parameters obtained noninvasively by in vivo 19F nuclear magnetic resonance (NMR) spectroscopy can be used to assess individual response to 5-FU chemotherapy. Eighteen patients with metastases of colorectal carcinoma treated with 5-FU were examined by 19F NMR at 1.5 T. The NMR signal intensity versus time curves were observed for the cytostatic and its catabolite alpha-fluoro-beta-alanine (FBAL). Clinical response to treatment was monitored by CT/MR imaging of the liver and carcinoembryonic antigen (CEA) levels in the serum. 5-FU levels observed in IV-treated patients correlate with volumes of metastases in the liver region examined with the 19F NMR coil (k = 0.77, p < .0001). 5-FU levels in patients at their initial 5-FU chemotherapy were related with clinical response determined after three cycles of treatment. In the group of patients with extensive liver involvement and IV treatment, responders (n = 3) had enhanced 5-FU levels compared to nonresponders (n = 3). FBAL data indicate an apparent saturation of 5-FU catabolism in the liver for 5-FU doses > 1 g infused during 10 min. Mean absolute concentrations of FBAL were about 1 mumol per gram liver tissue. 19F NMR spectroscopy could be used to guide dose escalation schemes or to assess the modulation of 5-FU metabolism by other drugs in combined chemotherapy. PMID- 8007781 TI - Eosinophilia-myalgia syndrome: findings at MR imaging and proton spectroscopy of the lower leg. AB - Five magnetic resonance (MR) studies of the lower leg were performed in three patients with eosinophilia-myalgia syndrome (EMS). The 1H spectroscopic and imaging findings were compared with seven examinations of age-matched healthy controls. Standard imaging with proton density-, T1-, and T2-weighted spin-echo (SE) sequences at 1.5 T showed marked atrophy of the calf muscles and slightly increased signal strength of muscle tissue in T2-weighted SE images. The application of frequency selective chemical shift imaging (SENEX) exhibited skin changes similar to those of scleroderma with increased water content and thickened cutis in the water selective images. In one patient the tibialis muscles showed irregular structures, but no fatty degeneration as demonstrated in the fat selective images. Proton signals from volume elements of (20 mm)3 within the soleus and gastrocnemius muscle were recorded by the PRESS localization method. A reduction of the creatine/water and the choline/water ratios was found in the 1H spectra from the EMS patients compared to the controls. Localized 1H spectroscopy exhibited modified distributions of the lipid signals in two EMS patients with slightly elevated signals from unsaturated fatty acids. The transverse relaxation of choline and creatine signals was accelerated in both examinations of one patient compared with the healthy controls. PMID- 8007782 TI - In vivo 7Li NMR diffusion studies in rat brain. AB - Lithium (Li) is widely used for the treatment of several psychiatric disorders and is the drug of choice in the treatment of bipolar disorders. The mechanism of action of Li, however, is unknown. A knowledge of brain Li concentration, its distribution in the brain, and its properties in the cellular microenvironments may contribute significantly towards the understanding of its function. We recently demonstrated by in vivo 7Li NMR the distribution and pharmacokinetics of Li ion in rat brain. We have made diffusion measurements of Li in the head and brain regions of anesthetized rats using the localized STEAM (stimulated echo acquisition mode spectroscopy) technique suitably sensitized to diffusion. In this paper we demonstrate for the first time the feasibility of Li diffusion measurements in the mammalian brain model with the ultimate goal of performing such studies on humans under Li therapy. PMID- 8007784 TI - Preliminary analysis of elasmobranch tissue using magnetic resonance imaging. AB - High resolution NMR images of sixgill shark (Hexanchus griseus) tissue from both horizontal and sagittal orientations are presented. Structures normally radiographically undetectable are visualised here with NMR. Proton density, spin lattice and spin-spin relaxation time maps as well as various relaxation weighted images show selective enhancement of different tissue types. Quantitative analysis of major anatomical features in the shark head is provided. PMID- 8007783 TI - Cardiovascular MR imaging: pressure-gating using the arterial pressure signal from a conventional ferromagnetic micromanometer-tip catheter. AB - We used the arterial pressure wave as a reliable trigger to synchronize MR imaging to the cardiac cycle. Pressure readings and MR images remained undistorted using a conventional ferromagnetic micromanometer-tip catheter. As a safe alternative to triggering to ventricular pressure, this approach allows varying the time relation between the trigger and the cardiac cycle while maintaining the advantages of pressure-gating. PMID- 8007785 TI - Abdominal wall desmoid mimicking intra-abdominal mass: MR features. AB - A case of abdominal wall desmoid which enlarged toward the liver and mimicked an intra-abdominal tumor is presented. T*2-weighted MR images clearly demonstrated the tumor's continuity with the rectus abdominis muscle. The case presented suggests MRI may provide more valuable information concerning the origin of a right-upper-quadrant mass than CT does. However, the nature of the signals and attachment which this case showed were so unusual for desmoids that this case has not been diagnosed accurately. PMID- 8007786 TI - Violence in the home: no more excuses. PMID- 8007787 TI - Health care cost and its containment: the dilemma of conflicting law, ethics and economics. PMID- 8007788 TI - The precarious situation of the medical student. PMID- 8007789 TI - Regarding "A moment with endocrinology and metabolism" Maryland Medical Journal November 1993. PMID- 8007790 TI - Medical neglect: what can physicians do? AB - Neglect is the most prevalent form of child maltreatment. Although the morbidity and mortality associated with it are significant, child neglect has attracted relatively little attention from professionals, the media, and the public. This article focuses on unmet, basic needs of children, particularly with regard to health care. In addition to defining neglect, the article discusses incidence, etiology, various forms of medical neglect, and principles for evaluation and management. PMID- 8007791 TI - Sexual abuse of children--a primer for physicians. AB - Sexual abuse of children is a problem that can present to any physician at any time. This article provides basic information about child sexual abuse and instructs physicians how to respond to abuse victims in a professionally responsible way that assures that the child is supported and protected. Legal definitions, prevalence, epidemiology, evaluation approaches, psychological problems, interviewing, the physical examination, sexually transmitted diseases, and management issues are discussed with emphasis on the physician's role. Finally, prevention is mentioned as the only real solution to this problem. PMID- 8007792 TI - Child abuse and wife abuse: the connections. AB - Wife abuse and child abuse frequently are interconnected. Survey and other data indicate abused children are likely to have abused mothers, and abused mothers are likely to have abused children. Physicians often can be more effective in protecting abused children by recognizing that the mother also may need protection. PMID- 8007793 TI - Family violence and the adolescent. AB - Violence within the family may have a major impact on child and adolescent development. Abused adolescents are more likely to engage in high-risk behaviors with serious consequences. Current adolescent health care is often inadequate in terms of psychosocial screening and anticipatory guidance. Physicians may play a significant role in reducing and preventing adolescent-related violence by increasing their efforts to identify those at risk and helping them with appropriate interventions. PMID- 8007794 TI - Children: the secondary victims of domestic violence. AB - Children who grow up in violent households can easily become the next generation of victims of violence or perpetrators of violence. Recognizing and responding to the special needs of children who witness domestic violence is essential in any effort to reduce or prevent cycles of abuse. As physicians focus on domestic violence, they are in a key position to identify children who are symptomatic from witnessing trauma and to make appropriate referrals. PMID- 8007795 TI - The use of art therapy in family violence. PMID- 8007796 TI - Physicians and attorneys: a partnership on behalf of the youngest victims of family violence. AB - Physicians play a vital role in court proceedings involving child abuse. This article describes the legal obligation of Maryland health care providers to report suspected cases of child abuse. It also discusses various types of testimony that may be required; reasons why physicians may be reluctant to testify; and why some types of testimony may be disallowed. PMID- 8007797 TI - Exercise-induced diarrhea: when to wonder. AB - Exercise-associated lower gastrointestinal symptoms seem to be a fairly common clinical finding occurring in anywhere from 10-50% of runners. However, it is unclear what percentage of those affected may have discrete medical conditions that are exacerbated by strenuous physical exertion. Perhaps, difficult physical training sessions function as a "stress test" for the colon. A case report of exercise induced diarrhea is presented with a discussion of the current medical literature and proposed management for the primary care sports physician. PMID- 8007798 TI - Exercise testing and training in patients with chronic heart failure. AB - Chronic heart failure (CHF) is a syndrome of impaired left ventricular (LV) function and cardiac output reserve that is associated with secondary compensatory adaptations including: LV hypertrophy and dilation, neuroendocrine activation, and vasoconstriction and redistribution of peripheral blood flow. The primary limitation in CHF is exercise intolerance characterized by fatigue and/or dyspnea during mild to moderate exertion. These symptoms are primarily attributed to impaired nutrient blood flow, cellular atrophy, and loss of oxidative function in skeletal muscle. Functional capacity in CHF is usually classified into four categories determined by symptom-limited exercise testing: normal > or = 7 METs; mild 5-7 METs; moderate 3-5 METs, severe < 3 METs. Exercise capacity in CHF is frequently unrelated to resting or exercise measures of LV function, e.g., LV ejection fraction (LVEF) and LV end diastolic pressure (LVEDP). Peak exercise heart rate and blood pressure are progressively attenuated in CHF due to baroreflex dysfunction and beta-receptor down regulation. Exercise training studies in selected patients with CHF (mild to moderate) have reported significant increases in peak VO2max, attributed to increases in peak leg blood flow O2 transport. Heart rate and lactate production during submaximal exercise are reduced compared with pretraining values. Potential training complications in patients with CHF include dysrhythmia, hypotension, and deterioration of cardiac status. The major benefit of moderate exercise training is improvement in tolerance to daily activities. However, the long term effect of exercise training on prognosis is currently not established. PMID- 8007800 TI - A justification for high resolution hematocrit measurement. AB - The purpose of this study was to determine the feasibility of using a 6" digital caliper and a 20x viewing microscope to measure hematocrit (HCT) from microhematocrit tubes. The reliability and validity of the digital caliper technique (DC) was simultaneously compared with that of the conventional "turntable" style microhematocrit method (MC) and the Coulter Counter hematocrit (CC) for a comprehensive comparison of the three methods. The reliability of the three methods was assessed by computing the standard error of the measurement (SEm) on triplicate readings of human blood samples. The SEm for MC, CC, and DC methods were 0.3555, 0.3004, and 0.1491, respectively. Validity was assessed by comparing the average of the triplicate HCT readings for each method with HCT determined by densitometry. Average HCT values (+/- SE) for the MC, CC, DC, and densitometry methods were 42.3 +/- 3.2, 42.4 +/- 3.4, 43.1 +/- 3.4, 43.7 +/- 3.3, respectively. Only the DC HCT values were not different from the densitometry HCT (P > 0.05). The MC and CC values were significantly lower (P < 0.01). It is concluded that accurate, highly precise measurements of HCT are obtainable using the digital caliper. The significance for this is the increased ability to perform extremely accurate measurement of changes in plasma volume. With this information, research labs can reliably measure smaller changes in plasma than was previously possible with commercial procedures. PMID- 8007799 TI - Normal cardiopulmonary responses during incremental exercise in 20- to 70-yr-old men. AB - Healthy men (N = 1424, age 20-70 yr) underwent a progressive incremental treadmill exercise test to volitional maximum. Cardiopulmonary variables were measured breath-by-breath. The aerobic power (VO2max) declined at an average yearly rate of 0.33 ml.kg.-1min-1, HRmax declined 0.685 beats.min-1.yr-1, and max O2 pulse declined at an annual rate of 0.115 ml.beat-1.kg-1*100. Gas exchange threshold (GET) expressed as percentage of VO2max was 58% and 69% in the youngest (20-30 yr) and oldest (61-70 yr) decades, respectively. The average decline in VE, Vt, f, and PETCO2 over the entire age range was 29%, 10%, 21%, and 7%, respectively. There were increases in VE/VO2, and VE/VECO2, from age 20-70 yr of 13% and 14%, respectively, but no changes across 5 decades in PETO2. Physical (height and weight) as well as life-style characteristics (leisure time activity, place of residency, smoking), were found to be potent predictors in most of the cardiopulmonary values at maximal exercise and therefore should be incorporated in the predictive equations for such variables. Normal response patterns of most cardiopulmonary variables throughout the range of exercise intensities were shown to be age-affected and thus should be standardized for age decades. PMID- 8007801 TI - Right to left differences in the ankle joint complex range of motion. AB - Rehabilitation of the ankle joint complex after injury is often considered complete when the injured ankle has the same range of motion and strength as the uninjured contralateral limb even though this symmetry has never been quantified. The purpose of this investigation was to determine whether there were differences in the ankle joint complex range of motion between right and left legs. Total right and left ankle joint complex range of motion was measured on 18 subjects using a fixture allowing six degrees of freedom. A four-camera video system was used to record all range of motion movements. The results indicated that total dorsiflexion-plantarflexion, eversion-inversion, and abduction-adduction ranges of motion were not significantly different between right and left legs. However, separate abduction and adduction differences occurred, with the right foot tending to abduct more than the left, while the left foot tended to adduct more than the right. These differences in the abduction and adduction range of motion may be inherent in the measuring device. As a result of this study, it appears that the contralateral ankle joint complex can be used as a measure for establishing restoration of total range of motion of the ankle joint complex following injury. PMID- 8007802 TI - Effect of aging on human skeletal muscle and motor function. AB - The percentage of Americans over the age of 65 yr is growing and this trend has heightened interest in aging research. In this review of human studies, comparisons, as a function of age, are made among the declines of VO2max, work endurance, muscle strength, total muscle cross-sectional area, muscle fiber number, spinal motor neuron number, and motor unit number. Declines in VO2max and total cross-sectional area of leg muscle begin in early adulthood. However, an accelerated loss of total muscle area and a decrease in muscle fiber number begins at about 50 yr of age. Losses in spinal motor neurons and motor units become apparent at about 60 yr of age. However, these findings were collected on different subjects. By better defining these temporal relationships in the same subjects, a more accurate cause and effect relationship may be obtained. Although muscle atrophy is attenuated by resistance training with aging, little is known about the effects of resistance training on the loss of spinal motor neurons, motor units, and muscle fiber number. The goal of this research would be to enhance the ability to promote as much function and independence of living as possible, i.e., increase the quality of life in our expanding elderly population. PMID- 8007803 TI - Mechanisms for the responses of cardiac muscle to physical activity in old age. AB - The decline of maximal cardiac output (Qmax) is a major factor responsible for the lower maximal oxygen consumption of elderly mammals. The lower Qmax is associated with aging-related decreases in maximal heart rate (HR-max) and maximal stroke volume (SVmax). The mechanism(s) for the slower HRmax, unchanged by exercise training, is unknown. The decrement in SVmax, however, can be improved, as shown by the enhanced systolic and diastolic properties of the elderly heart after exercise training. One major problem is diastolic dysfunction observed in the absence of disease. Diastolic dysfunction (a decrease in peak ventricular filling after systole or a prolonged relaxation of contracted muscle) results from in part a downregulation of the sarcoplasmic reticulum's (SR) calcium ATPase that sequesters cytosolic calcium via the hydrolysis of ATP. Exercise training of sedentary old mammals produces a faster relaxation and an upregulation of the SR calcium ATPase. Yet the characteristic shift of myosin toward the slower isoform is unaltered by exercise training. The molecular signals and mechanisms underlying these aging-related alterations in sedentary and physically active individuals are unknown. An enhancement of cardiac function by exercise training, though, is preserved in advanced age. PMID- 8007804 TI - Exercise and aging: autonomic control of the circulation. AB - This review describes age-related changes in autonomic control of the circulation during exercise and the associated effects on exercise capacity. The increase in heart rate during exercise becomes smaller with aging probably due to both less withdrawal of cardiac vagal tone and diminished beta-adrenergic responsiveness. The latter also appears to contribute to an attenuation in the left ventricular contractile response to exercise despite greater beta-adrenergic stimulation. At rest, muscle sympathetic nerve activity and arterial plasma norepinephrine spillover rates are elevated in older humans. With aging, sympathetically mediated vasoconstriction in nonactive muscle is augmented during brief dynamic exercise. Paradoxically, during more prolonged exercise increases in plasma norepinephrine concentrations/spillover rates are not greater with age. These age related changes do not adversely affect submaximal exercise performance at a particular % maximal oxygen consumption. However, the lower peak heart rate and attenuated left ventricular contractile response reduce maximal cardiac output, oxygen consumption, and exercise capacity. In older humans, aerobic exercise training lowers heart rate at rest, reduces levels of heart rate and plasma catecholamines at the same absolute submaximal workload, and, at least in men, improves left ventricular performance during peak exercise, but does not reduce, and may even increase, basal sympathetic nerve activity. PMID- 8007805 TI - Influence of age on skeletal muscle glucose transport and glycogen metabolism. AB - Age-related alterations in skeletal muscle carbohydrate metabolism can influence both health and performance. Exercising muscle glycogenolysis is accelerated in old, male rats compared with young animals, perhaps secondary to the age-related reduction in muscle oxidative capacity and blood flow during contractile activity. Muscle oxidative capacity and blood flow during exercise are also reduced in untrained older humans. Endurance training enhances muscle oxidative capacity and promotes muscle glycogen sparing during exercise by young and old rats. Resting muscle glycogen concentration is unchanged in old rats, but considerably reduced in untrained, older humans. Exercise training increases the muscle glycogen levels of older people. The concentration of GLUT-4 glucose transporter protein declines in some muscles of rats during growth and development, but remains stable thereafter. Exercise training can elevate the muscle GLUT-4 protein levels of both young and old humans. On the other hand, exercise training has been shown to increase the GLUT-4 values of adult, but not old rats. After one bout of exercise, muscle sensitivity for insulin-stimulated glucose transport is improved in young and old rats. These findings indicate that several age-related changes in muscle carbohydrate metabolism can be minimized by acute or chronic exercise. PMID- 8007806 TI - The influence of exercise and aging on immune function. AB - Immune function declines significantly with advancing age. While many components of the immune system are adversely affected, T cell-dependent functions are most dramatically compromised. This is most likely a result of involution of the thymus gland known to occur with age. Defects in T cell proliferative capacity/responsiveness, interleukin-2 production and receptor expression, signal transduction, and cytotoxicity are frequently cited problems associated with immunosenescence. The stress imposed by a single bout of exercise elicits a number of cardiovascular, thermoregulatory, and neuroendocrine responses that can directly influence many variables associated with the immune system. Consequently, during exercise, as well as into the subsequent recovery period, immune function can be significantly altered. Further, recent work has shown that as a result of endurance training adaptations in both baseline and exercising immune function can occur. However, extremely little is known regarding the interaction between exercise, aging and the immune system. Given that a number of age-related changes occur in many systems (e.g., neuroendocrine) known to alter immune function both at rest and during exercise, it would be of value to learn the extent to which both acute and chronic exercise influence immune function in the elderly. PMID- 8007807 TI - Skeletal muscle fiber type, resistance training, and strength-related performance. AB - The research goal was to attempt to clarify the consequences of increased strength on performance at submaximal exercise intensities. Eight subjects (4 males, 4 females) completed a 3-d.wk-1, 16-wk resistance training regimen. After training, upper (bench press, BP) and lower (parallel squat, PS) extremity strength were increased by 23% and 37%, respectively. Performance at the same absolute work rates as before training was increased by 30-159% following training depending on intensity and type of exercise. Performance at the same relative work rates (80%, 60%, 40%) remained unchanged by the training for both exercises. Prior to training, PS repetitions at 40% were correlated (r = 0.69, P < 0.05) with the percentage of slow-twitch (ST) fibers in the vastus lateralis muscle. There were similar relationships at 40% (r = 0.73) and at 60% (r = 0.83) for the PS exercise after training. However, the resistance program did not result in greater relative submaximal performance in individuals with a higher percentage of ST fibers. We conclude that strength improvement of up to 40% does not produce a strength-related performance deficit, when training and testing procedures are identical. Yet, these data do not rule out the potential of a strength-related repetition performance deficit. When subjects were equally divided by strength levels, those tested at the highest absolute resistance had significantly lower bench press repetition performance at 60% and 40% of the 1-RM than the subjects tested at the lowest absolute resistance. PMID- 8007808 TI - Moderate diet restriction alters the substrate and hormone response to exercise. AB - Substrate and hormone responses to submaximal exercise were studied in 10 overweight women (119-141% ideal body weight) to learn if a moderately restricted diet would influence the responses. Subjects consumed diets with adequate energy (ADEX), N = 5, or low energy (LDEX)--50% reduction in energy, N = 5. Three times during the 12-wk study, blood was drawn before and immediately following exercise; results were combined since there were no differences between replicates. Postexercise free fatty acids and glycerol increased to 465 +/- 27 mg.l-1 in LDEX but only to 245 +/- 19 mg.l-1 in ADEX. Postexercise insulin increased to 129 +/- 13 pmol.l-1 in LDEX, but did not increase in ADEX. Postexercise growth hormone increased to 10.5 +/- 1.0 microgram.l-1 in ADEX but only to 6.6 +/- 1.0 microgram.l-1 in LDEX. All postexercise increases within diet groups were highly significant (P < 0.0001), and the postexercise responses between diet groups were also different (P < 0.01). Respiratory gas exchange indicated that both groups increased fat utilization during exercise, but diet restriction altered postexercise hormones so that fat mobilization and utilization might be inhibited. The postexercise recovery period should be studied further to determine whether diet restriction results in a sustained altered hormone pattern that would curtail lipolysis and possibly limit body fat loss. PMID- 8007809 TI - EMG activities and ground reaction forces during fatigued and nonfatigued sprinting. AB - The present study was designed to investigate EMG activities and ground reaction forces during fatigued and nonfatigued running. Ten male sprint runners volunteered to run a maximal 20-m speed test, a 400-m time trial, and submaximal 20-m runs at the average speed of the first 100 m of the 400 m. During the latter stage of each run, ground reaction forces and EMG activity of four leg muscles were recorded. EMG activities were time averaged during three phases of running: preactivation, braking, and propulsion phase. The resultant ground reaction forces both in the braking (P < 0.001) and in the propulsion phase (P < 0.01) were greater in the maximal and submaximal 20 m than at the end of the 400 m. The averaged EMG during the braking phase (P < 0.01) and during the total ground phase (P < 0.05) was smaller in the submaximal 20 m than at the end of the 400 m. On the other hand the averaged EMG was greater during the maximal 20 m than at the end of the 400 m during the propulsion phase (P < 0.001) and during the total ground phase (P < 0.05). In addition, the more the preactivity increased the less the resultant ground reaction force decreased in the braking phase during the 400 m run (r = 0.77, P < 0.05). It was concluded that the role of the increased neural activation was to compensate for muscular fatigue and the preactivation had an important role in maintaining force production during the 400-m run. In addition, the fatigue was different in each working muscle. PMID- 8007810 TI - Does entrained breathing improve the economy of rowing? AB - A previous study has shown that subjects who entrain breathing during cycling exhibit a lower oxygen consumption (VO2) compared with random breathing. We sought to investigate the hypothesis that entrainment of breathing during rowing improved biomechanical economy (reduced VO2) compared with spontaneous breathing. A secondary hypothesis was that perceptual ratings of breathing difficulty would be lower with entrained breathing. Sixteen physically active male subjects (mean +/- SD age: 21 +/- 5 yr) with no previous rowing experience received instruction in rowing and then performed progressive incremental exercise on the variable resistance rowing ergometer (Concept II, Morrisville, VT). Peak VO2 was 53.1 +/- 5.4 ml.kg-1.min-1. At three subsequent visits subjects rowed at power productions of 50% and 75% of peak VO2 for 6 min each. At each visit they were randomized to a specific pattern of breathing: inspire during drive, expire during recovery; expire during drive, inspire during recovery; or spontaneous breathing. At the end of each session subjects rated "breathing difficulty" using the 0-10 category ratio scale. Analysis of variance revealed no significant differences in VO2, VO2/power production, or perceptual ratings at either intensity of exercise for the three different breathing patterns. Although our results do not support either the primary or secondary hypothesis, it is possible that any physiologic and/or perceptual benefits of locomotor-respiratory coupling might be specific for exercise mode or might require months to years of training. PMID- 8007811 TI - Muscle function at the wrist following 9 d of immobilization and suspension. AB - The purpose of this study was to evaluate the effects of 9 d of immobilization and partial suspension on muscle function at the wrist. Twelve female subjects (19-27 yr) wore a cast suspended from the neck by a sling that immobilized muscles acting on the wrist. Atrophy, muscle damage indicators, isometric and isokinetic strength, reaction time, speed of movement, and fatigability were assessed. Forearm muscle cross-sectional area decreased by 4.1% following immobilization and suspension. There was no indication that significant muscle degeneration occurred during immobilization or when muscles resumed normal function. Isometric strength for flexion and extension decreased by 29.3 and 32.5%, respectively. Concentric strength decrements for flexion, extension, pronation, and supination ranged from 8.9-21.7% at 2.11 and 3.16 rad.s-1. Eccentric strength decrements at 2.11 rad.s-1 for the same movements ranged from 12.5-18.5%. Fatigability was unaffected. Greater relative strength losses compared to decreased muscle cross-sectional area may be the result of a decrease in contractile protein density or unidentified neural factors following immobilization and partial suspension. However, neuromuscular control of reaction time was not affected. PMID- 8007812 TI - The effects of taper on performance in distance runners. AB - The purpose of this study was to determine if a 7-d systematic reduction in training volume or "taper" could improve distance running performance. Three groups of eight runners were examined: 1) run taper, 2) cycle taper, and 3) control. Training in the run taper group consisted of high-intensity intervals and an 85% reduction in training volume. The cycle taper group performed an equivalent amount of interval training as the run taper group, but each member exercised on a cycle ergometer. Control subjects continued normal training. A self-paced 5-km time trial served as the index of performance. The run taper group decreased 5-km time by 3% (1036.2 +/- 30.6 to 1006.8 +/- 28.2 s, P < 0.005). A significant decrease (P < 0.01) in submaximal oxygen consumption (6%) and calculated caloric expenditure (7%) at a running speed eliciting 80% of VO2max was also evident in the run taper group. Five-km performance and running economy were not altered in the cycle taper or control groups. These findings indicate that 7 d of tapered running improved distance running performance and running economy. A taper regimen of equivalent duration cycle training maintained performance in distance runners. PMID- 8007813 TI - Validity of percent body fat estimations in males. AB - The present investigation examined the validity of selected skinfold (Sum3), near infrared interactance (F5000 and F1000), and bioelectrical impedance (BIA) equations for estimating percent body fat (% fat) in young adult males (mean age +/- SD = 22 +/- 3 yr) by comparing the estimates with values obtained from underwater weighing. Fifty-seven Caucasian male (mean % fat +/- SD = 15.1 +/- 6.2) volunteers served as subjects. The statistical analyses included examination of constant error (CE), standard error of estimate (SEE), r, and total error (TE). The results indicated that the Sum3 equation had the lowest SEE (2.7% fat) and TE (3.6% fat) as well as the highest validity coefficient (r = 0.90). The F5000, however, had the lowest CE (-1.0% fat). Based on these findings, the Sum3 equation is recommended over the F5000 (TE = 4.2% fat), F1000 (TE = 6.1% fat), and BIA (TE = 5.0% fat) equations for estimating % fat in young adult males. PMID- 8007814 TI - Effect of drafting on heart rate in cross-country skiing. AB - The purpose of this study was to compare the heart rate responses during cross country skiing as a leading skier, as well as in a drafting situation, 2 m behind the leader. Six male cross-country ski racers, paired for VO2max skied a 2-km course (two loops of 1 km) using the skating techniques at a fixed speed (5.6 m.s 1) on two different occasions, once as a leading skier, the other as a drafter. A recovery period of 30 min was allowed between the two trials. Heart rates (HR) were monitored every 5 s during all performances. Capillary blood lactate concentrations were taken before and at 5 min posttrial. Results revealed that HR were significantly lower (154 vs 163 beats.min-1) when skiing behind another skier as opposed to leading. Lactate concentrations were not significantly different between the two trials. Results also revealed that projected frontal areas appeared to influence the effects of drafting such that the HR differences between the leading and the drafting situations were larger for smaller skiers drafting behind larger skiers. These results showed that skiing behind another skier in a ski race would be very advantageous when the situation is encountered and that coaches should use the drafting situation in training so that athletes can practice this energy-saving strategy. PMID- 8007815 TI - The accuracy of the ACSM and a new cycle ergometry equation for young women. AB - The purpose of this study was to determine the accuracy of the American College of Sports Medicine's (ACSM) equation for estimating the oxygen cost of exercise performed by women on a cycle ergometer. Sixty healthy, young females performed a five-stage submaximal cycle ergometry test. Results indicated the SEE for the predicted oxygen values ranged from 79-156 ml.min-1, with total errors (E) ranging from 107-275 ml.min-1. Correlations between the actual and predicted values ranged from r = -0.22 to r = 0.38. The r, SEE, and E were 0.96, 118, and 172, respectively for all of the power loads combined. A revised equation was developed based upon the actual VO2-power relationship. This equation appears as: VO2 (ml.min-1) = kgm.min-1 x 1.6 ml.min-1 + ((3.5 ml.kg-1.min-1 x kg body weight) + 205 ml.min-1). Cross validation was performed on an independent sample of 40 subjects. All of the SEE and E were lower and all of the correlations were higher at each power load in the validation sample. Since the revised equation is based on an actual VO2-power relationship, it would appear that it provides a more accurate depiction of the cycle ergometry VO2-power relationship for women. These facts support its use. PMID- 8007816 TI - The interaction between human transferrin and transferrin binding protein 2 from Moraxella (Branhamella) catarrhalis differs from that of other human pathogens. AB - The interaction between human transferrin and the transferrin binding proteins of Moraxella catarrhalis was studied by binding and affinity isolation experiments with transferrin and its derivatives. Competition binding experiments demonstrated that, compared to transferrin binding proteins in Neisseria meningitidis, the receptors in M. catarrhalis were more effectively blocked by iron-saturated transferrin than by the apo form of the protein. A combination of direct binding experiments and affinity isolation experiments demonstrated that this was due to a strong preference for binding of iron-saturated transferrin by transferrin binding protein 2 (Tbp2). Binding and affinity isolation studies also demonstrated that the C-lobe of human transferrin was fully capable of binding to M. catarrhalis transferrin binding protein 1 (Tbp1) but not to Tbp2. Neither the N-lobe nor a proteolytic derivative of human transferrin lacking only a portion of the C-terminus were capable of effectively binding to M. catarrhalis Tbp2, possibly implicating the involvement of several regions in the binding interaction. PMID- 8007817 TI - TNF alpha, IL-1 and O2- release by macrophages do not correlate with the anti mouse hepatitis virus 3 effect induced by interferon gamma. AB - Macrophages have been described to be important in determining the resistance of A/J mice or the susceptibility of BALB/c mice to the experimental infection with Mouse Hepatitis Virus 3 (MHV3). The interferon gamma (IFN gamma) activation of A/J and BALB/c mouse macrophages was shown to partially restrict the MHV3 replication only in macrophages from the resistant A/J mice. The activation by IFN gamma and/or infection with MHV3 showed that BALB/c mouse macrophages were capable of releasing tumor necrosis factor alpha (TNF alpha), interleukin 1 (IL 1) and anion superoxide (O2-), and A/J mouse macrophages were capable of releasing TNF alpha and IL-1 but not O2-. Comparable amounts of TNF alpha or IL-1 were released by IFN gamma-activated A/J or BALB/c mouse macrophages. Following MHV3 infection or IFN gamma activation and MHV3 infection, BALB/c mouse macrophages were always capable of releasing higher amounts of TNF alpha, IL-1 or O2- than A/J mouse macrophages, which correlated with their susceptibility to the virus infection. The data indicate that the anti-MHV3 effect induced by IFN gamma in A/J mouse macrophages is not related to the studied extrinsic activities of these cells. PMID- 8007818 TI - Protein profiles of Legionella pneumophila Philadelphia-1 grown in macrophages and characterization of a gene encoding a novel 24 kDa Legionella protein. AB - Legionella pneumophila Philadelphia-1 strain was grown in cultured macrophages of guinea pigs, hamsters, and A/J mice and the bacteria were purified by Percoll density gradient centrifugation without any detergent. Patterns of the bacterial proteins were compared by SDS-PAGE with those of organisms cultured in vitro. A 24 kDa protein was a major protein of intracellularly grown bacteria: its expression was about four times as much as a 24 kDa protein of agar-grown bacteria. At least three novel proteins (100, 65, and 16 kDa) that were not found on agar-grown bacteria were also observed. In this paper, we focused on the 24 kDa major Legionella protein expressed within macrophages. Western blot and N terminal amino acid analysis revealed that this protein is a novel protein different from Legionella proteins previously reported, including a 24 kDa macrophage infectivity potentiator protein (Mip). On the basis of amino acid sequence (MQRIKKI and IANAQGK), two kinds of oligonucleotides were synthesized and radiolabeled. Using these oligonucleotides as DNA probes, a 7.2 kb EcoRI digested DNA fragment encoding the 24 kDa protein was cloned into lambda ZAP II phage vector in Escherichia coli XL1-Blue. A 0.9 kb DNA fragment from the 7.2 kb fragment was further subcloned into pUC118 in E. coli CSR603 for maxicell analysis or XL1-Blue for DNA sequencing. Maxicells which carry recombinant plasmids consisting of the 0.9 kb DNA fragment and vector plasmid pUC118 expressed the 24 kDa protein. When the DNA fragment encoding the protein was sequenced, an open reading frame of 555 base pairs was identified. The inferred polypeptide had a molecular weight of 20 kDa and an estimated isoelectric point of 8.14. Both the nucleotide sequence and the deduced amino acid sequence were distinct from those of bacterial proteins reported previously, suggesting that the protein is a novel Legionella protein. PMID- 8007820 TI - [Beta-n-acetylglucosaminidase in urine as a sign of kidney damage in workers exposed to metallic mercury]. AB - The activity of beta-N-acetylglucosaminidase (beta-NAG) was determined in 41 workers of a chemical plant, exposed to metallic mercury, and in 10 controls. In addition, a routine urine examination was performed and the level of creatinine was measured in serum. The mercury excretion in urine in the exposed workers exceeded admissible biological concentrations three times, on average. In the group exposed to mercury the beta-NAG activity in urine was significantly higher than in the a control group. Several cases of trace proteinuria and microscopic haematuria were found in the exposed group. A mean beta-NAG activity in urine was significantly higher in those cases than in other persons. The study proved the usefulness of determinations of the beta-NAG activity in urine in assessing nephrotoxicity in workers exposed to metallic mercury. PMID- 8007819 TI - DNA sequence analysis of an allelic variant of the Actinobacillus pleuropneumoniae-RTX-toxin I (ApxIA) from serotype 10. AB - The structural gene encoding Actinobacillus pleuropneumoniae-RTX-toxin I (ApxIA), one of the major hemolytic and cytolytic toxins of the organism, was cloned from serotype 10. The nucleotide sequence data showed that the gene from serotype 10 was 98% identical to that from serotype 1 at both DNA and amino acid levels. The sequence difference was found to localize at the 3' terminal region of the gene. We then analyzed the 3' terminal region of the apxIA gene from other serotypes, 5a, 5b, 9 and 11, using polymerase chain reaction-amplified DNA fragments. Results of DNA sequence indicated that apxIA gene can be divided into the original form including serotypes 1, 9 and 11, and the allelic variant including serotypes 5a, 5b and 10. These gene products, ApxIA proteins, appear to have different second structures at the carboxyl terminal proximal region. PMID- 8007821 TI - [Assessment of genotoxic activity of azo dye thiadiazole derivatives with the help of a structural chromosome aberration test]. AB - The genotoxic activity of 2-methyl aminothiadiazole and azo dyes series of azo thiadiazole-1,3,4 was assessed using chromosome aberration in vivo and in vitro. The test in vivo was performed on mice bone marrow cells and in vitro on human blood lymphocytes. Derivatives of 2-naphthol, p-chlorophenol, pyro-catechin, resorcin and gamma resorcin acid were tested. The study did not reveal any toxic effect of azo dies in doses used in the test. Their use in the synthesis of more complex substances can be recommended. PMID- 8007822 TI - [Results of spirometric examinations in workers engaged in production of iron manganese alloys]. AB - Spirometric examinations were performed in 205 workers engaged in production of iron-manganese alloys. It was found that mean values of FEV1, FEV1%, PEFR, MEF25% 75% VC and MMF were significantly lower in persons above 40 years of age, smokers and in those suffering from chronic bronchitis in comparison with people below the age of 40, non-smokers and persons free from chronic bronchitis. No relationship between the length of employment and the ventilation capacity was found. PMID- 8007823 TI - [Certain behavior and attitudes of workers associated with dental care provided in the workplace]. AB - Dental care at places of employment was assessed under the Polish edition of the International Collaborating Studies of Oral Health Outcomes. The study was focused particularly on the use of primary conservative dental care (accessibility of dental care in polyclinics provided by institutions), reasons why workers are not willing to see dentists in their polyclinics as well as the judgement of the quality of primary dental care (the degree to which this kind of care is available for and approved by workers, the extent of positive judgements of primary conservative dental care). The analysis indicated rather strong disapproval of dental care rendered by polyclinics with view to ill-functioning of polyclinics rather than to their existence. PMID- 8007824 TI - [Activities of the occupational hygiene section of the State Sanitary Inspection Service in 1992]. AB - The organizational and employment structures as well as activities of the occupational hygiene section of the sanitary and epidemiological services in Poland in 1992 are discussed. The information presented is based on special forms (Mz-50) and progress reports provided by individual units. Special emphasis is put on problems faced by these services in supervising placedu of employment. The need for regular training of occupational hygienists (public health managers) and improving qualifications of workers with secondary education employed in the area of occupational hygiene is stressed. An in-depth reform of occupational hygiene units is required as their present condition, as far as staff and equipment are concerned inables them to provide regular monitoring of harmful factors occurring in the occupational environment. PMID- 8007825 TI - [Quality assurance of examinations performed by laboratories of the State Sanitary Inspection Service]. AB - An accredited laboratory means that its competence in performing particular tests and examinations is officially recognised. Requirements concerning testing laboratories are specified in the European Standard EN 45001 and in the Guide ISO/ICE-25. When applying for an accreditation laboratories of the State Sanitary Inspectorate have to develop new or adjust existing systems of quality assurance in accordance with the aforesaid recommendations. The system of laboratory quality assurance should be described thoroughly in the quality manual and backed up by an appropriate documentation. An application for accreditation should be preceded by the following steps: setting up of a team of persons responsible for quality assurance policy, drawing up criteria for assessing testing methods and procedures, promoting principles of quality assurance and introducing necessary corrections, formulating an accreditation application form which should comprise: the range of expected accreditation, kind of investigations to be performed and methods to be applied. An application together with the quality manual should be submitted to the Central Bureau for Product Quality Assurance in Warsaw--the only office which grants accreditation in Poland. PMID- 8007826 TI - [The role of long-term exposure to lead in the pathogenesis of hypertension- review of epidemiologic studies]. AB - Epidemiological studies aimed at assessing the relationship between a long-term exposure to lead and hypertension were reviewed. The analysis of mortality based on blood lead levels (600-800 micrograms/l) indicated that the magnitude of exposure to lead was in general rather high. Deaths caused by cerebrovascular diseases proved to be the main risk in this group of population. The confirmation of this finding was looked for in studies of morbidity carried out in the working population and among people living in areas of high exposure to lead. The studies confirmed a significant relationship between the magnitude of exposure to lead and the level of systolic pressure. During those studies it was also attempted to monitor main confounding factors such as smoking and alcohol consumption. A clinical effect, namely an increased systolic pressure was, however, very low not exceeding several mm Hg and in terms of the difference in blood lead levels was equal to 10 micrograms/l. Despite all efforts mechanisms responsible for an increased pressure resulting from exposure to lead have not yet been identified. It seems most likely that disorders in metabolism of calcium ions leading to a spasm of muscular coat of vessels are a causal factor. There is an urgent need for assessing delayed effects of exposure to lead. Such studies should be performed in groups of persons with good evidence to prove their exposure to this factor. It would be helpful to describe individual doses corresponding to the magnitude of exposure to individual persons under study but that seems to be rather impossible in retrospective studies.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8007827 TI - [Involvement of free radicals in lead poisoning]. AB - The following proves that free radicals are involved in lead poisoning: An enolamine form of 5-aminolevulinic acid (ALA), a haem precursor which accumulates in the body of lead poisoned patients undergoes fast autooxidation with concomitant generation of reactive oxygen species. The transmembrane potential and calcium ions fluxes of isolated rat mitochondria are strongly affected by ALA. This toxic effect is inhibited by antioxidant enzymes. Induction of antioxidant enzymes' activity was observed in lead-exposed workers. PMID- 8007828 TI - [Mites as a cause of allergic diseases in humans]. AB - The paper presents current views on the role of acarina in pathogenesis of allergic diseases and their occurrence in the human environment. The allergic species of acarina present both in the occupational and community environments were investigated. Basic methods for obtaining allergen extracts as well as immunological tests used for detecting allergy to those allergens are described. Some modes of combating acarina in the human environment are discussed. PMID- 8007829 TI - [Classification of mines in Poland by group radiation exposure of miners]. AB - The computer data base on individual occupational exposure to ionizing radiation among miners (established at the Nofer Institute of Occupational Medicine, Lodz) was used to classify all Polish non-uranium mines (coal, copper, lead-zinc and chemical raw material mines) according to values of the so-called group radiation exposure (in man-sivert units). In total 72 coal mines, 13 chemical raw material mines and 10 metal ore mines employing 246,580, 3,080, 17,820 miners, respectively, were assessed. The analysis of individual annual miners exposures indicated the highest exposure to ionizing radiation in this group of workers in comparison with other occupational groups in Poland. An equivalent occupational group dose in Poland amounts to 1,480 man-siverts. Out of this dose 96.4% is received by miners, 2.5% by X-ray workers, 0.7% by workers of isotope laboratories and 0.1% by physiotherapeutists working in health resorts. PMID- 8007830 TI - On-line processing of textual illustrations in the visuospatial sketchpad: evidence from dual-task studies. AB - We present evidence that the comprehension of illustrated text makes use of the visuospatial sketchpad component of working memory. The results from three experiments demonstrate that the comprehending of texts that are accompanied by pictures interferes with the performance of a spatial short-term memory task more than does the comprehending of texts that have no pictures. A fourth experiment demonstrates that the interference is found only when there is a requirement to comprehend the text; that is, the simple presentation of the texts and their pictures did not degrade performance on the spatial task. Finally, we show that the comprehension of illustrated texts does not differentially interfere with a verbal short-term memory task. These results are consistent with the claim that illustrations accompanying a text encourage the formation of a spatial mental model with the use of the working memory's sketchpad. PMID- 8007831 TI - Studying related pictures can reduce accuracy, but increase confidence, in a modified recognition test. AB - In 14 experiments, a dissociation occurred between subjects' accuracy on a forced choice recognition test and their confidence in their choice. Nature pictures (e.g., Lake A) were shown. Later, the subjects were asked to choose the picture that they remembered, given the target (Lake A) and a novel picture (Lake C) as alternatives, and rated their confidence in their choice. When the subjects also studied a related picture (Lake B), their accuracy often decreased while their confidence increased. The dissociation cannot be explained by signal detection theories of recognition, which assume that strength determines both accuracy in a forced-choice test and confidence. Instead, familiarity with general themes may give people the illusion that they are accurately remembering details. PMID- 8007832 TI - Regressive eye movements and sentence parsing: on the use of regression contingent analyses. AB - Altmann, Garnham, and Dennis (1992) recently advocated the use of a regression contingent analysis in eye movement studies dealing with parsing of sentences containing temporary structural ambiguities. Using experimental sentences preceded by referentially supportive contexts, they demonstrated a different pattern of results when regressive eye movements were eliminated from the data set than when regressions were included. The regression-contingent analysis that they used involves an implicit assumption that regressive eye movements are a necessary consequence of subjects' being garden pathed. We report some data which demonstrate that garden path effects are sometimes even stronger in the absence of regressions and, thus, argue that readers can be garden pathed without making regressions. PMID- 8007833 TI - Intention and awareness in perceptual identification priming. AB - We show that inferences can be made about differences in retrieval intentionality between direct and indirect tests, even when those tests involve different physical cues. When the presence of old items was not mentioned (indirect test condition), we observed a crossed double dissociation between perceptual identification priming and recognition memory as a function of a manipulation of data-driven versus conceptually driven processing at encoding. When subjects were instructed to use their memory to help them identify test items (intentional retrieval condition), priming could be expressed as a monotonically increasing function of recognition memory performance. This reversed association (Dunn & Kirsner, 1988) between priming and recognition memory cannot be accommodated by a model that views intentional retrieval as common to the tests and attributes the crossed double dissociation to an intertest difference in physical cues and associated processes. A posttest questionnaire measure indicated that awareness of the presence of previously encountered items was ubiquitous among indirect test subjects. Crossed double dissociations between direct and indirect measures can therefore be ascribed to differences in retrieval intentionality but not necessarily to differences in subjective awareness of the past. PMID- 8007835 TI - The formation of flashbulb memories. AB - A large group of subjects took part in a multinational test-retest study to investigate the formation of flashbulb (FB) memories for learning the news of the resignation of the British prime minister, Margaret Thatcher. Over 86% of the U.K. subjects were found to have FB memories nearly 1 year after the resignation; their memory reports were characterized by spontaneous, accurate, and full recall of event details, including minutiae. In contrast, less than 29% of the non-U.K. subjects had FB memories 1 year later; memory reports in this group were characterized by forgetting, reconstructive errors, and confabulatory responses. A causal analysis of secondary variables showed that the formation of FB memories was primarily associated with the level of importance attached to the event and level of affective response to the news. These findings lend some support to the study by R. Brown and Kulik (1977), who suggest that FB memories may constitute a class of autobiographical memories distinguished by some form of preferential encoding. PMID- 8007837 TI - Comparing models of rule-based classification learning: a replication and extension of Shepard, Hovland, and Jenkins (1961). AB - We partially replicate and extend Shepard, Hovland, and Jenkins's (1961) classic study of task difficulty for learning six fundamental types of rule-based categorization problems. Our main results mirrored those of Shepard et al., with the ordering of task difficulty being the same as in the original study. A much richer data set was collected, however, which enabled the generation of block-by block learning curves suitable for quantitative fitting. Four current computational models of classification learning were fitted to the learning data: ALCOVE (Kruschke, 1992), the rational model (Anderson, 1991), the configural-cue model (Gluck & Bower, 1988b), and an extended version of the configural-cue model with dimensionalized, adaptive learning rate mechanisms. Although all of the models captured important qualitative aspects of the learning data, ALCOVE provided the best overall quantitative fit. The results suggest the need to incorporate some form of selective attention to dimensions in category-learning models based on stimulus generalization and cue conditioning. PMID- 8007834 TI - Word recognition in two languages and orthographies: English and Greek. AB - Word recognition processes of monolingual readers of English and of Greek were examined with respect to the orthographic and syntactic characteristics of each language. Because of Greek's direct letter-to-sound correspondence, which is unlike the indirect representation of English, the possibility was raised of a greater influence of the phonological code in Greek word recognition. Because Greek is an inflected language, whereas English is a word order language, it was also possible that syntax might influence word recognition patterns in the two languages differentially. These cross-linguistic research questions were investigated within the context of a letter cancellation paradigm. The results provide evidence that readers are sensitive to both the orthographic and the linguistic idiosyncracies of their language. The results are discussed in terms of the orthographic depth hypothesis and the competition model. PMID- 8007836 TI - The role of segmentation in prospective and retrospective time estimation processes. AB - In five experiments, we investigated the effects of the segmentation level of an interval on its perceived duration. A prospective paradigm and an absolute time estimation method were used in two experiments, and in two others we used a retrospective paradigm and a comparative estimation method. A positive relationship was obtained between segmentation level of the estimated interval and its perceived duration under retrospective-comparative conditions for both auditory and tactual stimuli, but no relationship was found under prospective absolute conditions. The paradigm, estimation method, and segmentation level were jointly manipulated in the fifth experiment. The impact of segmentation was significant under retrospective (both absolute and comparative) and close to significant under prospective-comparative conditions. These findings suggest that high-priority events are perceived and coded as contextual changes and that the impact of segmentation on time estimation is mediated by memory processes. PMID- 8007838 TI - Uncoupling of occlusion from ATP hydrolysis activity in sarcoplasmic reticulum (Ca2+ + Mg2+)-ATPase. AB - The uncoupling of Ca2+ transport from ATP hydrolysis in the sarcoplasmic reticulum (Ca2+ + Mg2+)-ATPase by trypsin digestion was re-investigated by comparing ATPase activity with the ability of the enzyme to occlude Eu3+ (a transport parameter) after various tryptic digests. With this method, re examination of uncoupling by tryptic digest of the ATPase revealed that TD2 cleavage (Arg-198) had no effect on either occlusion or ATPase activity. Digestion past TD2 in the presence of 5 mM Ca2+ and at 25 degrees C resulted in the loss of about 70% of the ATPase activity, but no loss of occlusion. Digestion past TD2 in the presence of 5 mM Ca2+, 3 mM ATP, and at 25 degrees C resulted in a partially uncoupled enzyme complex which retained about 50% of the ATPase activity, but completely lost the ability to occlude Eu3+. Digest past TD2 in the presence of 5 mM Ca2+ and 3 mM AMP-PNP (a non-hydrolyzable ATP analog) at 25 degrees C resulted in no loss of occlusion, thus revealing the absolute requirement of ATP during the digest to eliminate occlusion. From these findings we conclude that uncoupling of Ca2+ transport from ATPase activity is possible by tryptic digestion of the (Ca2+ + Mg2+)-ATPase. Interestingly, only after phosphorylation of the enzyme do the susceptible bond(s) which lead to the loss of occlusion become exposed to trypsin. PMID- 8007839 TI - Use of the fluorescent probe Laurdan to investigate structural organization of the vesicular stomatitis virus (VSV) membrane. AB - We have used 6-dodecanoil-2-dimethylaminonaphtalene (Laurdan) to study the membrane fluidity of Vesicular Stomatitis Virus (VSV) during virus activation at acidic pH 5.8). The fluorescence properties of Laurdan provide a unique possibility to study lipid organization because of the different excitation and emission spectra of this probe in the gel and liquid crystalline phase. Acidification to pH 5.8 (the pH which triggers VSV fusion with target membranes) generates a decrease in VSV membrane fluidity that could be reversed perfectly after neutralization. We conclude that lipid reorganization of the VSV membrane in the endocytic vesicles is needed for virus activation. PMID- 8007842 TI - Risk management education for the office staff. An important ingredient to successful malpractice prevention. PMID- 8007840 TI - Inactivation of firefly luciferase and rat erythrocyte ATPase by ultrasound. AB - Previous work in our laboratories has shown that, amongst other effects, irradiation of frog skin with low intensity ultrasound causes reductions in the chemical driving force of the short-circuit current. This indicated that either the Na/K dependent ATPase or ATP availability were being reduced. We measured the effect of ultrasound irradiation on ATP and NA/K-dependent ATPase from inverted erythrocyte ghosts and on firefly luciferin and luciferase activity. Our findings demonstrate that ultrasonic cavitation-induced sonochemical reactions were responsible for irreversible inactivation of luciferase and ATPase but had little or no effect on ATP and luciferin. We measured the levels of hydrogen peroxide generated by ultrasound under the conditions of our experiments and found that it could account for only part of the enzyme inactivation observed. Free radical scavengers/antioxidants were capable of fully protecting the enzymes from ultrasound-induced inactivation. These findings demonstrate that, in addition to hydrogen peroxide, free radicals generated by ultrasound are responsible for the effects. PMID- 8007841 TI - Effect of free radical scavengers on changes in ion conductance during exposure to therapeutic ultrasound. AB - Ultrasound has been used in physical therapy for > 4 decades. Recent studies indicate that non-thermal mechanisms such as cavitation are involved in the observed effects. Free radicals and other highly reactive compounds are known to form during sonochemical reactions associated with acoustic cavitation. Using frog skin as a biological model, the possibility that the increase in ionic conductance (Gt) upon exposure to therapeutic ultrasound is due to the effect of free radicals generated by sonochemical reactions, was investigated. It was found that the presence of cystamine, cysteamine and sodium ascorbate significantly reduced the increase in conductance caused by the exposure to 300 mW/cm2 (1 MHz CW) therapeutic ultrasound. The attenuation in the effects was dependent on the concentration of the radical scavengers/antioxidants used, the incubation time, and the intensity of ultrasound. The effects were also dependent on the lipid solubility of free radical scavengers/antioxidants. The time constant for the recovery process of Gt in the presence of free radical scavengers and antioxidants after exposure to ultrasound was found to be not significantly different from control. These results suggest that the increase in Gt due to ultrasound is induced by free radicals and other reactive species generated from acoustic cavitation. This study provides an indirect evidence to the contingent that free radicals are generated and act inside the cells. Furthermore, the radical scavengers and antioxidants used provide protection from oxidative damage without being involved in the recovery of Gt towards steady state values after sonication. PMID- 8007843 TI - Why patients sue for malpractice. What do patients think of your practice? PMID- 8007844 TI - Deposition preparedness is essential to malpractice defense. Experienced defense attorneys offer advice for physicians. PMID- 8007845 TI - Practice parameters: a silk purse or a sow's ear? PMID- 8007846 TI - Practice parameters: more than 1,500 have been developed since 1989 and more are in the works. PMID- 8007847 TI - Update on occupational disease reporting in Michigan. PMID- 8007848 TI - Practice parameters. Physician input is key. PMID- 8007849 TI - "Successful breastfeeding"--what success? PMID- 8007850 TI - Cup-feeding: an alternative method. PMID- 8007851 TI - Breast-feeding twins. PMID- 8007852 TI - RCM Standing Practice Group paper 1. To monitor or not to monitor: the midwife's use of electrocardiographic forms of monitoring the fetus in labour. PMID- 8007853 TI - Germany: healing the wounds. Part 2: Eastern Germany. PMID- 8007854 TI - Peace, justice and health. PMID- 8007855 TI - Integrating general practice medical education. The North Queensland model. PMID- 8007856 TI - The dead do tell tales. PMID- 8007857 TI - Graduate medical schools in Australia. PMID- 8007858 TI - Australian graduate medical schools. A progress report. PMID- 8007859 TI - Tuberculosis: medical students at risk. AB - In 1979 an outbreak of tuberculosis occurred in medical students at the University of Sydney. Eight of 35 Mantoux-negative students who attended the autopsy of an immunosuppressed patient with unsuspected active tuberculosis became infected and one developed clinical disease. A report of the incident was prepared for publication because it supported the then controversial University policy of recommending BCG vaccination to medical and dental students in a country where the reported prevalence of tuberculosis is very low. The report was never published, mainly in order to protect the privacy of the individual students involved, but also because it was felt by the administration of the time that it might undermine confidence in infection control procedures in the autopsy room. The original report, updated and reproduced here, suggested that tuberculosis might be an emerging nosocomial problem. This has been all too clearly realised since its re-emergence as an opportunistic infection in AIDS patients. Worldwide, the problem of antibiotic resistance in Mycobacterium tuberculosis provides an added risk of a return to the situation which prevailed early this century when tuberculosis was a major occupational risk for young health care workers. Infection often restricted career choices, even in those whose disease was relatively benign. Our purpose in bringing this incident to light after so many years is to point out the relevance of the extensive studies of the problem which were conducted in the 1930s and 1940s to the current situation and to suggest that health care students are vulnerable to airborne infections as well as those spread by inoculation injuries. In retrospect, our 1979 conclusions about prospects for preventing nosocomial tuberculosis appear optimistic. PMID- 8007860 TI - Needlestick injury in medical students. AB - OBJECTIVE: To determine the incidence of needlestick injuries and the prevalence of hepatitis B vaccination among medical students, dentistry students, and hospital staff. DESIGN AND SUBJECTS: Anonymous survey of final year medical students and dentistry students enrolled at Sydney University in 1992, and nursing staff and doctors employed in the wards and emergency department of Royal Prince Alfred Hospital, Sydney. RESULTS: During their clinical training, 22% of medical students and 72% of dentistry students had received one or more contaminated, penetrating "sharps" injuries. Of hospital staff, 50% of ward nurses, 71% of ward doctors, and 50% of emergency staff had received this type of injury during the previous two years. Students were significantly more likely to be vaccinated against hepatitis B than hospital staff (P < 0.001)--98% of medical students and 95% of dentistry students had received a full course of vaccination. The rate of vaccination among hospital staff ranged from 79% in emergency staff to 85% in ward nurses. CONCLUSIONS: Clinical students sustain needlestick injuries at a rate comparable with hospital personnel and therefore face a significant risk of exposure to transmissible pathogens, including hepatitis B virus, HIV, and hepatitis C virus. The rate of hepatitis B vaccination is high among clinical hospital staff and almost universal among medical and dentistry students. PMID- 8007861 TI - Drug and alcohol abuse by doctors. AB - OBJECTIVE: To determine whether doctors who abuse substances differ from controls in terms of their physical and psychological well-being, and their marital and occupational functioning. DESIGN AND PARTICIPANTS: The 44 doctors concerned in all cases of substance abuse which came before the Medical Board of Victoria between 1984 and 1990 were invited to complete a demographic questionnaire, psychological tests and a semi-structured interview. A control group of 42 doctors, obtained from the Medical Register, was also invited, and the groups were compared. SETTING: The study was carried out at St Vincent's Hospital, Melbourne, under the auspices of the Medical Board of Victoria. RESULTS: Questionnaires were returned by 70% of the drug-dependent doctors and 83% of the controls. However, interviews were given by only 20% of the drug-dependent doctors. The groups differed significantly in terms of marital status (P < 0.002), overall health (P < 0.003), general wellbeing (P < 0.0009), and having experienced physical illness (P < 0.02) and psychiatric illness (P < 0.006) since graduation. No differences were found on the standardised questionnaires; this may reflect successful treatment. CONCLUSION: Substance abuse in medical practitioners is a major problem and is associated with considerable morbidity. Prevention and early intervention are crucial. PMID- 8007862 TI - A case-control study of the sequelae of childhood sexual assault in adult psychiatric patients. AB - OBJECTIVE: To determine if there is any association between childhood sexual assault and maladaptive coping behaviour in adult life. DESIGN: A case-control study. SETTING AND PATIENTS: Data from 707 psychiatric patients consecutively examined by one psychiatrist in a rural practice were analysed. Forty-four female patients who were victims of childhood sexual assault were identified and were age matched in a random manner with 88 control patients who denied being sexually assaulted as children. RESULTS: The two groups were similar in occupational level, employment and marital status, and the only diagnostic difference between them was that there was a trend in the sexually assaulted group for more of these patients to be diagnosed as having personality disorder. On a variety of other outcome factors, however, the two groups differed widely. The sexually assaulted women were more frequently victims of domestic violence (odds ratio [OR], 6.4), made suicide attempts (OR, 3.4) and abused alcohol (OR, 3.0) or tranquillisers (OR, 4.6) more often than the non-assaulted women. There was a definite association between childhood sexual assault and maladaptive coping behaviour in adult life, although the association is not necessarily causal, and the childhood sexual assault may, in fact, be a symptom of familial neglect. CONCLUSION: This study provides clear evidence of the need to follow up victims of childhood sexual assault and reinforces the importance of enquiring about this trauma. PMID- 8007863 TI - Soft-tissue sarcoma of the extremity. Experience with limb-sparing surgery. AB - OBJECTIVES: To assess the degree to which limb-sparing surgery is implemented in patients with soft-tissue sarcoma, and its outcome. DESIGN AND SETTING: A detailed review of 40 patients who were all tertiary referrals to one surgeon, and general review of all 215 patients with sarcoma treated in South Australia between 1986 and 1992. INTERVENTIONS: Conservation of the limb by wide resection or marginal resection of soft tissue, combined when necessary with radiotherapy. Amputation was used when limb conservation failed or was not possible. MAIN OUTCOME MEASURES: Median survival time after treatment. RESULTS: Limb-sparing treatment was successful in 37 of the group of 40 patients. Thirty-two patients received adjuvant radiotherapy, and 19 received chemotherapy. Median survival time was 35 months. Review of all 215 patients with sarcoma revealed a higher initial amputation rate and a lower use of combined treatment methods than in our series. Twenty-six patients (65%) were initially incorrectly diagnosed before referral, resulting in a median delay in treatment of 16 weeks. CONCLUSIONS: The concept of limb-sparing surgery is well established, but is not yet as widely practised for limb sarcomas as it could be. Delay in diagnosis is a significant problem. PMID- 8007864 TI - Farm health and safety in rural New South Wales. Insights through qualitative research. AB - OBJECTIVES: To determine the appropriate content and format of a farm health and safety training program for rural health professionals, and to explore issues in rural health care relevant to the health and safety education of the farming community. DESIGN: Qualitative research by focus group and individual interviews with health care professionals and members of the farming community. SETTING: Four rural New South Wales towns, with a range of agricultural activities. PARTICIPANTS: One hundred and sixteen health care professionals and 58 people who lived or worked on farms were interviewed. RESULTS: Suggestions were made for field days and seminars to provide information on agricultural hazards. Doctors were the most common first contact for health care but were rarely involved in preventive health care. Members of the farming community largely believed that they got the health care that they requested from their doctors. Community health teams provided preventive health care but rarely received referrals from doctors. Doctors often saw the farming community according to a stereotype of "the man on the land" that discouraged preventive health care interventions. CONCLUSION: Current patterns of health care service in rural communities inhibit the opportunities for effective farm health and safety education. A training program in farm health and safety could meet the needs of rural health professionals and the community if it encouraged greater use of a wider range of health care professionals as providers of preventive health care. PMID- 8007865 TI - Survivors of self-inflicted firearm injury. A liaison psychiatry perspective. AB - OBJECTIVE: To examine the clinical profile and, in particular, the psychopathology of 33 survivors of self-inflicted firearm injury. DESIGN: An eight-year retrospective case history analysis. Information was obtained from databases in the Psychiatry, Trauma and Medical Records departments of Westmead Hospital. RESULTS: In the sample most survivors of self-shooting were young men who did not suffer from major depression or psychosis. Most shootings occurred in the context of interpersonal disputes with sexual partners or family members. CONCLUSIONS: Most patients who survive self-inflicted firearm injuries have shot themselves impulsively in a crisis, are not psychotic, and have ready access to firearms. Psychiatric care is usually given in the trauma ward. Close cooperation is required between psychiatric and surgical teams in management. Recommendations to assist in the more accurate assessment of patients with self-inflicted firearm injury include: careful scrutiny of alleged accidental shootings; the inclusion of police information in the assessment; routine drug screening and determination of blood alcohol level; repeated interviews and corroboration of patient claims by family and friends; and psychiatric review of all patients with self-inflicted injury. PMID- 8007866 TI - Consideration of narcolepsy in the differential diagnosis of chronic fatigue syndrome. AB - OBJECTIVE: To justify the inclusion of narcolepsy in the differential diagnosis of patients with chronic fatigue. CLINICAL FEATURES: We report three patients aged 17 (two women and one man) and one woman aged 45 who had been diagnosed as having chronic fatigue syndrome (CFS). They had no psychiatric illness. Their main problem was severe daytime sleepiness, presenting as "tiredness and fatigue". The history, sleep study and multiple sleep latency test suggested a diagnosis of narcolepsy. INTERVENTION: Treatment with methylphenidate resulted in complete resolution of symptoms in two patients and significant improvement in the other two. CONCLUSIONS: The differential diagnosis of CFS requires the exclusion of other conditions. If daytime sleepiness is a major complaint, other symptoms of narcolepsy should be sought and the diagnosis confirmed with sleep study and a multiple sleep latency test. PMID- 8007867 TI - Is there a role for drug therapy in the treatment of urinary incontinence in the elderly? PMID- 8007868 TI - Medical informatics. PMID- 8007869 TI - Autopsy and the use of tissues removed at autopsy. The Royal College of Pathologists of Australasia. PMID- 8007870 TI - Fluorouracil and cardiotoxicity. PMID- 8007871 TI - Undergraduate perceptions of country practice. PMID- 8007872 TI - Smoking prevalence among senior medical students. PMID- 8007873 TI - Apparent change in the male:female ratio of incidence of urolithiasis in California. PMID- 8007874 TI - Dealing with the public: issues for the intern. PMID- 8007876 TI - Protocols for vegetative patients. PMID- 8007875 TI - Consensus statement on management of hypertension. PMID- 8007877 TI - Vitamin K and childhood cancer. PMID- 8007878 TI - Prevalence of penicillin resistant Streptococcus pneumoniae. PMID- 8007879 TI - Rural access line: a tool for improving communication between rural GPs and hospital specialists in Western Australia. PMID- 8007880 TI - Guidelines on the management of paediatric middle ear disease. PMID- 8007881 TI - Hib meningitis immediately after vaccination. PMID- 8007882 TI - Relative infrequency of microsporidial infection in HIV infected patients in Queensland. PMID- 8007883 TI - Prophylaxis for the prevention of infective endocarditis. PMID- 8007884 TI - Cell-mediated immunity in combat veterans with post-traumatic stress disorder. PMID- 8007885 TI - Flu vaccination of the elderly: room to improve. PMID- 8007886 TI - Hypertension and diabetes in older people. PMID- 8007887 TI - Severe complications following a "barium swallow" investigation for dysphagia. PMID- 8007888 TI - Medical Quality Assurance Programme. PMID- 8007889 TI - Adult advanced life support. PMID- 8007890 TI - Treatment of haemophilia in Australia. PMID- 8007891 TI - Preoperative assessment and perioperative consideration of the geriatric patient. PMID- 8007892 TI - Some aspects of sedating patients in the intensive care unit. PMID- 8007893 TI - The pathogenesis and prevention of central venous catheter-related infections. AB - Vascular catheters are a major source of nosocomial infections. Definite diagnosis of catheter-related infections should include the use of quantitative catheter cultures or differential quantitative blood cultures. The skin and catheter hub are the two major sources for the introduction of the colonizing organisms. Both microbial (slime) and host (fibrin and fibrinectin) factors contribute to the formation of the biofilm which is essential for the adherence and maintenance of the colonization. Staphylococci and Candida are the leading causative agents. Prolonged duration of catheterization, thrombogenic catheter material, frequent manipulation of the catheter, improper aseptic insertion and maintenance techniques, tranparent plastic dressings, contaminated skin solutions, location of the catheter, and possibly multilumen central venous catheters (CVC) are risk factors predisposing to infections. Preventive measures include a skilled infusion therapy team, topical disinfectants such as chlorhexidine and topical antibiotics, silver impregnated cuffs (for short term CVC), coating catheters with antiseptic agents and maximal barrier precautions during insertion. Exchanging central venous catheters over a guidewire might be useful diagnostically but have not been proven to be of any therapeutic or preventive potential. PMID- 8007894 TI - Closed circuit coasting from high flow isoflurane anesthesia. AB - Closed circuit coasting after high flow isoflurane-N2O anesthesia was used in 30 patients undergoing operations expected to last more than one hour. Near the end of the operation, the circuit was closed by shutting off anesthetics and reducing oxygen flow to that necessary to maintain constant end-tidal circuit volume throughout the duration of coasting (Tc). End-tidal isoflurane concentration of 0.5% was a safe target for coasting. Good correlation was found between Tc and anesthetic delivery duration (TAD). An adequate TC for the first hour of TAD was 15 minutes followed by 11 minutes more for each subsequent hour of TAD. The technique is safe, simple, economic, predictable and practical. PMID- 8007895 TI - Right upper lobe atelectasis after upper urinary surgery in the lateral decubitus position--case report. AB - Pulmonary atelectasis is a known complication of urinary tract surgery performed in the lateral decubitus position. In 1946 Faulconer reported 8 cases of atelectasis associated with the use of the lateral decubitus position and elevated kidney rest. Several papers have indicated an influence of anesthesia and muscle relaxation as well as position in the development of atelectasis. We present a case of right upper lobe (RUL) atelectasis following left radical nephrectomy under general anesthesia in the right lateral decubitus position, successfully treated with saline lavage and bronchoscopic suction. PMID- 8007896 TI - Disclosing rationing decisions: a reply to Paul S. Appelbaum. PMID- 8007897 TI - Trust and informed consent to rationing. PMID- 8007898 TI - Improving health: measuring effects of medical care. AB - The impact of medical care on the quality and length of life of the population has been poorly documented. The rapid growth of evidence of efficacy of therapy for individual medical conditions now offers the opportunity to create an inventory of benefits. A method for creating such an inventory is described, as is its application to a selection of condition-treatment pairs, chosen for their high incidence of prevalence, their serious outcomes, and the demonstrated efficacy of their treatment. An aggregate effect of medical care on life expectancy is found to be roughly five years during this century, with a further potential of two years. Although there is no overall index of quality of life analogous to life expectancy, our inventory demonstrates the enormous burden of pain, suffering, and dysfunction that afflicts the population for which medical care can provide a large measure of relief. PMID- 8007899 TI - The changing boundaries of the American hospital. AB - The American hospital faces two different possible futures. In one, the hospital continues to expand into outpatient, home health, and long-term-care services and remains the center of the changing health care system. In the other, competition in each of these domains from independent health plans, which do not have to contend with the high wages, technological imperatives, and bureaucratic inertia of large hospital organizations, pushes the hospital to a peripheral role as provider of ever-diminishing acute inpatient services. The choice between these two futures will be made based on the efficiencies of vertical integration relative to market contracting. Transactions cost economics is used to analyze the changing boundaries of the hospital organization, particularly with respect to outpatient diagnostic and surgical clinics, home health agencies, and long term-care facilities. PMID- 8007900 TI - Privatization, system membership, and access to home health care for the elderly. AB - Home health agency (HHA) access based on organizational and market factors is considered, employing a theoretical model of isomorphism for organizational factors and ecological and economic theories for market factors. Data derive from 1986 and 1987 telephone surveys that randomly sampled 185 HHAs from nine metropolitan areas in five states. Results show that competition limits restrictions on access; for-profit status and system membership increase the likelihood that clients will be refused for financial reasons. Findings support the isomorphism theory that fewer access and other behavioral differences appear within systems: nonprofits and for-profits tend to behave alike within systems, whereas freestanding nonprofits are less likely than their for-profit counterparts to refuse access. Findings for system members may account for some of the problems of legitimacy experienced by nonprofit health care organizations. PMID- 8007901 TI - Differences in treatment of ischemic heart disease at a public and a voluntary hospital: sources and consequences. AB - A study of hospital patients with ischemic heart disease reports that patients in a public hospital received fewer needed diagnostic tests, surgeries, and follow up visits for their conditions than their private hospital counterparts. Factors in the hospitals' organizational environments and the patients' social backgrounds were observed to have an impact on content of treatment and to affect patient as well as provider perspectives on the quality of care. To facilitate the analysis, data were collected from four sources: direct observation of the care of each patient on rounds and at the bedside; interviews with physicians concerning the rationale for their decisions; a process-oriented chart audit assessing the appropriateness of care; and an extensive home interview with each patient three months following hospital discharge to establish further use of health services, health status, and satisfaction with care. PMID- 8007902 TI - Alternative volume performance standards for Medicare physicians' services. AB - The Omnibus Budget Reconciliation Act of 1989 (OBRA89) established volume performance standards (VPSs) as a key element in Medicare physician reform. This policy requires making choices along three dimensions: the risk pool, the scope and nature of the standard, and the application of the standard. VPSs have most effectively controlled expenditures and changed physician behavior when they use states as the risk pool, are composed entirely of Medicare Part B services, and establish per capita utilization targets. The institution of separate standards for voluntarily formed physician groups would pose substantial administrative challenges and has the potential to effect adverse outcomes. Instead, Congress should continue to encourage prepaid plans for the purpose of lowering health care use. Under current law, VPSs will be used to adjust future price increases. Congress may not wish to emulate the example of countries that have imposed expenditure ceilings to control costs unless the current method of using VPSs proves unsuccessful. PMID- 8007903 TI - Alcoholism and income: the role of indirect effects. AB - The potential pathways by which alcoholism might affect income are examined using data on males from the New Haven site of the Epidemiologic Catchment Area (ECA) data set to illustrate important indirect, and direct, effects of alcoholism on income. The detrimental indirect effects occur through reduction of educational attainment and increased probability of divorce. Because both educational attainment and marriage positively influence income, the adverse impact of alcoholism on both of these variables translates into lower income for alcoholics. The implications should lead researchers to distinguish more carefully between the direct and indirect costs of this condition. Policy analysts also should explore the financial impact of early onset when they look at overall costs. Because this has often been underestimated, fewer resources are devoted to prevention and treatment of alcoholism than a considered awareness of the problem would indicate is warranted. PMID- 8007904 TI - PHOs can lead to strong, profitable relationships. PMID- 8007905 TI - On collective clout and agents of change. PMID- 8007906 TI - The bottom line: PHOs benefit hospitals, not doctors. PMID- 8007907 TI - Chiropractic article misleading. PMID- 8007908 TI - Physician-hospital integration Ramsey Clinic style. PMID- 8007910 TI - Reform must be a shared responsibility. PMID- 8007909 TI - Bicycle-motor vehicle collisions. Epidemiology of related injury incidence and consequences. AB - This study investigated the incidence, consequences, and possible risk factors for injuries resulting from non-fatal bicycle-motor vehicle collisions during a one-year period in Minnesota. A study of 925 non-fatal collisions involving individuals 12 years of age and older in 1984 found an inverse relationship between age and collision incidence, with especially high rates identified for those between the ages of 12 and 14 (164 per 100,000) and 15 and 19 (71 per 100,000). Male bicyclists had consistently higher collision rates among all age groups. In a survey of the 925 individuals (64.3% response rate) 95% reported sustaining injuries as a consequence of the collisions. Twenty-one percent said they had not fully recovered from their injuries approximately two years post injury, while 26% reported persistent problems. These results show a high incidence of collisions under certain conditions and suggest protective measures to make bicycling safer on our nation's roadways. PMID- 8007911 TI - Communicating DNR orders in non-hospital settings. PMID- 8007912 TI - The physician-hospital integration sensation. PMID- 8007913 TI - The PHO phenomenon. PMID- 8007914 TI - Providing universal health care coverage. PMID- 8007915 TI - AZT reduces HIV transmission to newborns. PMID- 8007916 TI - Minnesota reports 2,000th AIDS case. PMID- 8007917 TI - Extracting the pertinent from the irrelevant. PMID- 8007918 TI - In the driver's seat on the road to reform. PMID- 8007919 TI - Visions and missions improving medicine--not! PMID- 8007920 TI - Infant cries: physiology and assessment. AB - It is generally agreed that the infant communicates physiological and psychological distress to caregivers by crying. Crying that is atypical in amount, intensity, duration, or quality could signal a physiological problem before the problem becomes obvious in other ways. Thus, cry analysis could soon become an important tool in early identification of infants at risk. To better assess neonatal cry sounds, nurses need some background in cry physiology. This article describes the evolution of cry sound production, presents the contemporary theories on the physiology of cry sound production, explains how cries are acoustically categorized and analyzed, and highlights the implications for infant caregivers. PMID- 8007921 TI - When the mother of a premature infant uses a breast pump: what every NICU nurse needs to know. AB - Although pumps may seem readily available in the community, their effectiveness, as measured by the amount of negative pressure they generate and their cycling pattern of pressure and release, must be considered when recommending a particular model to the breast feeding mother of a premature infant. The neonatal nurse needs to assist the mother as she selects a breast pump by helping her pick the one that works best for her and by instructing her in its appropriate use. Such use needs to be oriented to obtaining maximum milk volume with minimal expenditure of energy without incurring breast or nipple pain or trauma. Sound breast pump recommendations and pumping instructions based on a clear understanding of the anatomy and physiology of the breast and knowledge of the lactation process will enable many women to give their infants the best possible nutritional and emotional start in life even before direct breast feeding begins. PMID- 8007922 TI - Pulmonary function testing in the critically ill neonate, Part III: Case studies. AB - Accurate monitoring of respiratory status is of vital importance for the bedside nurse caring for the critically ill neonate. Pulmonary function testing can be utilized to effectively diagnose and quantitate lung disease in infants. Data obtained can be integrated into the nursing assessment and facilitate appropriate nursing interventions. The case studies provided in Part III of this series illustrate the utility of such testing in neonates with a range of illnesses and different diagnostic and therapeutic dilemmas. Case study one is an infant with chronic lung disease complicated by bronchospasm, case study two is an infant with bronchomalacia, and case study three demonstrates fine tuning of the ventilator in an infant with respiratory distress syndrome. Every study describes the usefulness of pulmonary function testing on a specific patient, each with different pulmonary pathology. These case studies, and the discussion in parts I and II of this series, illustrate the value of integrating pulmonary function data with ongoing clinical assessment to optimize the care of the sick or convalescing neonate. Tests ordered on a routine and/or as-needed basis will provide detailed information on the infant's pulmonary status that may be readily available at the infant's bedside. The neonatal nurse's involvement in requesting, performing, and interpreting these tests may enhance the treatment of the infant in intensive care. PMID- 8007924 TI - At the crossroads of health care reform. PMID- 8007923 TI - Safety and efficacy of sufentanil therapy in the ventilated infant. AB - This pilot study examined the safety and efficacy of sufentanil in the ventilated neonate. Informed parental consent for study participation was obtained for eight infants who were admitted to the neonatal intensive care unit and required analgesic/sedative therapy as part of their medical management to support mechanical ventilation. An intravenous loading dose (0.2 microgram/kg) was administered over 20 minutes, followed by a continuous infusion (0.05 microgram/kg/hour). Whole blood samples were collected prior to onset of sufentanil therapy, immediately following the loading dose, and 24 hours after the start of the continuous sufentanil infusion for analysis of beta-endorphin and sufentanil serum content. Heart rate, respiratory rate, and blood pressure were recorded as a routine part of medical management. The ventilatory efficiency index (VEI) and ventilation index (VI) were calculated before and after sufentanil therapy. Four male and four female infants were admitted to this study; the mean gestational age was 37 weeks, and weight was 2,970 gm. Sufentanil therapy appeared to be well tolerated, as evidenced by a lack of nursing observations noting changes in heart rate or mean arterial pressure. VEI values increased in four subjects, and VI values decreased in six subjects. Overall, the mean increase in VEI was 19 percent; the decrease in VI was 27 percent. The beta endorphin serum content decreased in all subjects, and nurses did not report any signs of patient discomfort. Serum sufentanil content was undetectable. Sufentanil appears to be a suitable agent to provide analgesia/sedation in the neonatal patient under the experimental conditions of this study.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8007925 TI - Incubator covers: health or hazard? PMID- 8007926 TI - Kangaroo care. PMID- 8007927 TI - The chest x-ray findings in retained lung fluid. PMID- 8007928 TI - Instruments in neonatal research: measuring preterm infant feeding ability, Part I: Bottle feeding. PMID- 8007929 TI - Drug compatibilities and infusion sites. AB - Many medications commonly used in the NICU are compatible, but are not routinely coinfused. By minimizing infusion sites, nurses contribute to protecting our smallest patients against infection and stress. No single handbook or resource provides comprehensive information about drug compatibilities. Clinicians must cross-reference several sources to guide their practice. PMID- 8007930 TI - A mother and doctor's perspective. PMID- 8007931 TI - Medical-care expenditures attributable to cigarette smoking--United States, 1993. AB - Cigarette smoking is the most important preventable cause of morbidity and premature mortality in the United States; however, approximately 48 million persons aged > or = 18 years are smokers (1), and approximately 24 billion packages of cigarettes are purchased annually (2). Each year, approximately 400,000 deaths in the United States are attributed to cigarette smoking (3) and costs associated with morbidity attributable to smoking are substantial (4). To provide estimates for 1993 of smoking-attributable costs for selected categories of direct medical-care expenditures (i.e., prescription drugs, hospitalizations, physician care, home-health care, and nursing-home care), the University of California and CDC analyzed data from the 1987 National Medical Expenditures Survey (NMES-2) and from the Health Care Financing Administration (HCFA). This report summarizes the results of the analysis. PMID- 8007932 TI - Risk for traumatic injuries from helicopter crashes during logging operations- southeastern Alaska, January 1992-June 1993. AB - Helicopters are used by logging companies in the Alaska panhandle to harvest timber in areas that otherwise are inaccessible and/or unfeasible for conventional logging (because of rugged terrain, steep mountain slopes, environmental restrictions, or high cost). The National Transportation Safety Board (NTSB) investigated six helicopter crashes related to transport of logs by cable (i.e., long-line logging*) that occurred in southeastern Alaska during January 1992-June 1993 and resulted in nine fatalities and 10 nonfatal injuries. This report presents case investigations of these incidents. PMID- 8007933 TI - Adult blood lead epidemiology and surveillance--United States, 1992-1994. AB - CDC's National Institute for Occupational Safety and Health Adult Blood Lead Epidemiology and Surveillance program (ABLES) monitors elevated blood lead levels (BLLs) among adults in the United States (1). Twenty-two states currently report surveillance results to ABLES. Beginning in 1993, ABLES began detecting both new cases and persons with multiple reports over time. In this report, ABLES provides data for the first quarter of 1994 and compares annual data for 1993 and 1992. PMID- 8007934 TI - NIOSH alert: request for assistance in preventing organic dust toxic syndrome. PMID- 8007935 TI - [Metabolism under total parenteral nutrition: the influence of different compositions of energy substrate]. AB - Metabolism under total parenteral nutrition according to different compositions of energy substrate was studied using expiratory gas analysis in preoperative and postoperative esophageal cancer patients. The patients were derived from Group G (only glucose was administrated as a non-protein energy source) and group G+F (glucose and fat were administrated as non-protein energy sources). In the preoperative study, there was a significantly positive correlation between non protein RQ and the energy sufficiency ratio (energy intake/BEE) and non-protein RQ in group G+F was lower than in group G at the same total energy intake. It was revealed that there was a limit to oxidation of exogenous glucose and whether exogenous energy sources are efficiently utilized or not depends on two factors, namely total energy intake and the combination of glucose and fat. In the postoperative study, fat was efficiently utilized in group G+F and glycogen recycling was dominant over fat recycling. Urinary epinephrine, 17-OHCS and 17-KS excretion were significantly high in group G+F. It was clear that energy metabolism and hormonal effect differ with exogenous energy substrate. PMID- 8007936 TI - [Three dimensional architecture of the microvascular systems of the skin in wound healing processes of normal and streptozotocin-induced diabetic rats]. AB - Fine vascular architectures in the wound healing process of streptozotocin (STZ) induced diabetic rat skin were studied by scanning electron microscope with newly designed high pressure resin injection method. In the normal rat skin, the new method successfully demonstrated the hitherto unknown subepidermal fine capillary network which continuously surrounded the pillosebaceous tissues. In wound healing processes after combined resection of skin and fascia, vascular regeneration occurred from both the border and the base of the lesion. The new vasculatures from the border of dermis demonstrated concentric array of loops extending toward the center of the lesion. The direct budding emerged from the capillary network of the exposed muscle surface. Subepidermal vasculatures of the intact back skin of STZ-induced diabetic rats showed coarse and poorer network pattern. Increased number of anastomoses between arterioles and venules, insufficiently dilated arterioles distal to the A-V shunt were the other findings which may imply the increased shunt blood flow and consequent poor peripheral dermal circulation. PMID- 8007937 TI - [Analysis of glucose metabolism in patients with esophageal cancer by PET: estimation of hexokinase activity in the tumor and usefulness for clinical assessment using 18F-fluorodeoxyglucose]. AB - We evaluated glucose metabolism of esophageal cancer by PET using 18F fluorodeoxyglucose (FDG), in order to investigate its clinical usefulness. In 11 advanced cases k3 value reflecting hexokinase activity and Ci/Cp ratio expressing FDG uptake were calculated from radioactivity in the tumor (Ci) and the plasma (Cp). Both k3 and Ci/Cp were well correlated with hexokinase activity from the resected specimen, so Ci/Cp was considered to be a convenient index for clinical assessment of esophageal cancer. Forty-two cases before treatment revealed high accumulation of FDG, and 41 showed more than 2.0 of Ci/Cp. But, 10 normal controls and one esophageal benign tumor showed less than 2.0. As for 13 post operative cases, 6 cases out of 7 with recurrence showed more than 2.0 for Ci/Cp, but all 6 cases of non-recurrent cases showed less than 2.0. FDG PET is an useful tool for differential diagnosis of recurrence. The clinicopathological findings were investigated in 26 resected cases. Age, location, vertical extension, histologic feature, lymph node metastasis and histologic stage were not correlative with Ci/Cp. As for DNA ploidy pattern, aneuploidy group showed significantly high Ci/Cp rather than diploidy group. Eight cases which showed more than 5.0 of Ci/Cp resulted in poor prognoses compared with 14 cases which showed less than 5.0. PMID- 8007938 TI - [Use of radiopaque markers for the diagnosis and management of small bowel obstruction]. AB - Radiopaque markers were used for the diagnosis and management of small bowel obstruction (SBO) due to adhesion in 50 patients. Conservative therapy was begun after the patients received a capsule containing 20 radiopaque markers. The movement of the markers in the gastrointestinal tract was evaluated on X-P after 6, 12, 24, and 48 hours. On supine abdominal X-P, the abdomen was divided by a straight line connecting the right costophrenic angle and the left anterior superior iliac spine, thus defining an upper and lower abdominal segment. After 24 hours, the number of markers in the upper abdominal segment was 4.1 +/- 4.5 in 30 patients who recovered within 7 days, and 16.7 +/- 3.8 in 20 patients who required more than 7 days of conservative therapy (mean +/- SD). In cases requiring long-term management with conservative therapy, the markers in the small bowel were calculated on a daily basis using X-P. On day 7, there were more than 10 markers in the small bowel of 7 patients who underwent surgery. By using radiopaque markers, it was possible after 24 hours to differentiate patients with SBO who would need long-term management, and to determine the limits of conservative therapy and the timing for surgery. PMID- 8007939 TI - [Changes of arterial CO2 (PaCO2) and urine output by carbon dioxide insufflation of the peritoneal cavity during laparoscopic cholecystectomy]. AB - We studied on the effects of carbon dioxide insufflation during laparoscopic cholecystectomy on the arterial blood gas analysis and urine output. Intra abdominal pressure was increased up to either 10cmH2O or 15cmH2O, and we compared the PaCO2 values before and during insufflation. Both increase of PaCO2 and decrease in pH were larger in intra-abdominal pressure of 15cmH2O than 10cmH2O. In the intra-abdominal pressure 15cmH2O group, the increase of PaCO2 by CO2 peritoneal insufflation was significantly larger in operative time of more than 60 minutes group than in less than 60 minutes group, but no significant changes were observed in 10cmH2O group. In the group of obesity index of more than 120, elevation levels of PaCO2 by CO2 insufflation were significant, but in the group of less than 120 no significant elevation were observed. The tendency that the urine output during operation was decreased as increase of intra-abdominal pressure or operative time, but the obesity had no definite effects on urine output. Insufflation of the abdomen with CO2 caused large changes in PaCO2 or pH in the patients with a previous history of major cardiopulmonary disorder. It was shown that the low insufflation pressure and short operative time is good for the maintenance of normal physiological state. PMID- 8007940 TI - [Surgical treatment for postinfarction ventricular septal perforation]. AB - Between August 1981 and August 1992, operation for ventricular septal perforation (VSP) after acute myocardial infarction (AMI) was performed in 12 patients and the results were studied. During this period, medical treatment was attempted as a standard therapy for more than two weeks after AMI, followed by operation. However, only four patients received elective operation two weeks after the onset of AMI. Regarding the relationship between the preoperative circulatory status and timing of surgery, elective operative could not be performed in seven patients showing a pulmonary to systemic flow ratio (Qp/Qs) of more than 3.0, while four out of five patients with a ratio of less than 3.0 received operation more than two weeks after the onset of AMI. Two patients with severe right heart failure after the repair of VSP died on table without weaning from the pump. Ten operative survivors were weaned from the pump without any difficulty of hemostasis and intraaortic balloon pumping was removed after operation. However, three patients died of multiple organ failure which had been deteriorating before operation. Postoperative activity improved to New York Heart Association Functional Class I or II in six survivors for the late follow-up period. In the case of high Qp/Qs due to VSP, early operation is recommended to prevent multiple organ failure. PMID- 8007941 TI - [A clinical study of respiratory complication after cardiopulmonary bypass, with special reference to complement activation, WBC and granulocyte elastase]. AB - Complement activation and it's influence on lung injury were studied in 20 patients undergoing cardiopulmonary bypass (CPB). Anaphylatoxins increased remarkably to 3130 +/- 1770 ng/ml in C3a, 2480 +/- 2530 ng/ml in C4a and granulocytes were significantly fewer in left atrium (LA) than right atrium (RA) during CPB. Granulocyte elastase (GEL) was significantly higher in LA than RA at the time of reperfusion. Postoperative respiratory index was well correlated with C3a and GEL. We concluded that lung injury after CBP was caused by anaphylatoxin which aggregated granulocyte in pulmonary vasculature and released GEL during CPB, and anaphylatoxin was produced not only by using CBP but in patient's lung. PMID- 8007942 TI - JAK2 associates with the beta c chain of the receptor for granulocyte-macrophage colony-stimulating factor, and its activation requires the membrane-proximal region. AB - The high-affinity receptor for granulocyte-macrophage colony-stimulating factor (GM-CSF) consists of a unique alpha chain and a beta c subunit that is shared with the receptors for interleukin-3 (IL-3) and IL-5. Two regions of the beta c chain have been defined; these include a membrane-proximal region of the cytoplasmic domain that is required for mitogenesis and a membrane-distal region that is required for activation of Ras, Raf-1, mitogen-activated protein kinase, and S6 kinase. Recent studies have implicated the cytoplasmic protein tyrosine kinase JAK2 in signalling through a number of the cytokine receptors, including the IL-3 and erythropoietin receptors. In the studies described here, we demonstrate that GM-CSF stimulation of cells induces the tyrosine phosphorylation of JAK2 and activates its in vitro kinase activity. Mutational analysis of the beta c chain demonstrates that only the membrane-proximal 62 amino acids of the cytosolic domain are required for JAK2 activation. Thus, JAK2 activation is correlated with induction of mitogenesis but does not, alone, activate the Ras pathway. Carboxyl truncations of the alpha chain, which inactivate the receptor for mitogenesis, are unable to mediate GM-CSF-induced JAK2 activation. Using baculovirus-expressed proteins, we further demonstrate that JAK2 physically associates with the beta c chain but not with the alpha chain. Together, the results further support the hypothesis that the JAK family of kinase are critical to coupling cytokine binding to tyrosine phosphorylation and ultimately mitogenesis. PMID- 8007944 TI - Identification of a transcriptional activator-binding element in the 27 kilodalton zein promoter, the -300 element. AB - By utilizing a homologous transient-expression system, we have shown that a 58-bp sequence from the gamma-class 27-kDa zein promoter, spanning from -307 to -250 relative to the transcription start site, confers a high level of transcriptional activity on a truncated plant viral promoter. The transcriptional activity mediated by the 58-bp sequence is orientation independent, and it is further enhanced as a result of its multimerization. A similarly high level of transcriptional activity was also observed in protoplasts isolated from leaf tissue-derived maize suspension cells. In vitro binding and DNase I footprinting assays with nuclear protein prepared from cultured endosperm cells revealed the sequence-specific binding of a nuclear factor(s) to a 16-nucleotide sequence present in the 58-bp region. The nuclear factor binding sequence includes the 300 element, a cis-acting element highly conserved among different zein genes and many other cereal storage protein genes. A 23-bp oligonucleotide sequence containing the nuclear factor binding site is sufficient for binding the nuclear factor in vitro. It also confers a high level of transcriptional activity in vivo, but in an orientation-dependent manner. Four nucleotide substitutions in the -300 element drastically reduced binding and transcriptional activation by the nuclear factor. The same nuclear factor is abundant in the developing kernel endosperm and binds to the -300 element region of the 27-kDa or the alpha-class zein promoter. These results suggest that the highly conserved -300 element is involved in the common regulatory mechanisms mediating the coordinated expression of the zein genes. PMID- 8007943 TI - Stat4, a novel gamma interferon activation site-binding protein expressed in early myeloid differentiation. AB - Interferon regulation of gene expression is dependent on the tyrosine phosphorylation and activation of the DNA-binding activity of two related proteins of 91 kDa (STAT1) and/or 113 kDa (STAT2). Recent studies have suggested that these proteins are substrates of Janus kinases and that proteins related in STAT1 are involved in a number of signalling pathways, including those activated in myeloid cells by erythropoietin and interleukin-3 (IL-3). To clone STAT related proteins from myeloid cells, degenerate oligonucleotides were used in PCRs to identify novel family members expressed in myeloid cells. This approach allowed the identification and cloning of the Stat4 gene, which is 52% identical to STAT1. Unlike STAT1, Stat4 expression is restricted but includes myeloid cells and spermatogonia. In the erythroid lineage, Stat4 expression is differentially regulated during differentiation. Functionally, Stat4 has the properties of other STAT family genes. In particular, cotransfection of expression constructs for Stat4 and Jak1 and Jak2 results in the tyrosine phosphorylation of Stat4 and the acquisition of the ability to bind to the gamma interferon (IFN-gamma)-activated sequence of the interferon regulatory factor 1 (IRF-1) gene. Stat4 is located on mouse chromosome 1 and is tightly linked to the Stat1 gene, suggesting that the genes arose by gene duplication. Unlike Stat1, neither IFN-alpha nor IFN-gamma activates Stat4. Nor is Stat4 activated in myeloid cells by a number of cytokines, including erythropoietin, IL-3, granulocyte colony-stimulating factor, stem cell factor, colon-stimulating factor 1, hepatocyte growth factor, IL-2, IL 4, and IL-6. PMID- 8007946 TI - Elevated frequency of microsatellite mutations in TK6 human lymphoblast clones selected for mutations at the thymidine kinase locus. AB - A major question in carcinogenesis is, How can a normal cell accumulate multiple mutations in different genes on different chromosomes, when the mutation rate of each gene is in the range of 10(-8) to 10(-5) per cell division? We hypothesize that many mutations may not be isolated events but rather are accompanied by concomitant mutations elsewhere in the genome. To test this hypothesis, 331 independent clones selected for new mutations at the thymidine kinase (TK) locus on chromosome 17q, and 243 nonselected control clones were examined for mutations in 12 random microsatellite loci dispersed throughout the genome. A total of 24 second-site mutations were identified in the TK mutant clones, compared with 3 in the control clones not selected for mutations at TK. The mutations include small deletions, insertions, and loss of heterozygosity. These results provide evidence that a global trans-acting mutagenic process exists in human cells. The activation of this process could be responsible for causing multiple essential mutations in tumor cells. PMID- 8007945 TI - A pleiotropic element in the medium-chain acyl coenzyme A dehydrogenase gene promoter mediates transcriptional regulation by multiple nuclear receptor transcription factors and defines novel receptor-DNA binding motifs. AB - We previously identified a complex regulatory element in the medium-chain acyl coenzyme A dehydrogenase gene promoter that confers transcriptional regulation by the retinoid receptors RAR and RXR and the orphan nuclear receptor HNF-4. In this study we demonstrate a trans-repressing regulatory function for the orphan receptor COUP-TF at this same nuclear receptor response element (NRRE-1). The transcriptional regulatory properties and receptor binding sequences of each nuclear receptor response element within NRRE-1 are also characterized. NRRE-1 consists of four potential nuclear hormone receptor hexamer binding sites, arranged as [<--1-(n)s-2-->-3-->(n)4<--4], three of which are used in alternative pairwise binding by COUP-TF and HNF-4 homodimers and by RAR-RXR heterodimers, as demonstrated by mobility shift assays and methylation interference analysis. Binding and transactivation studies with mutant NRRE-1 elements confirmed the existence of distinct retinoid, COUP-TF, and HNF-4 response elements that define novel receptor binding motifs: COUP-TF homodimers bound sites 1 and 3 (two hexamer repeat sequences arranged as an everted imperfect repeat separated by 14 bp or ER14), RAR-RXR heterodimers bound sites 1 and 2 (ER8), and HNF-4 homodimers bound sites 2 and 3 (imperfect DR0). Mixing cotransfection experiments demonstrated that the nuclear receptor dimers compete at NRRE-1 to modulate constitutive and ligand-mediated transcriptional activity. These data suggest a mechanism for the transcriptional modulation of genes encoding enzymes involved in cellular metabolism. PMID- 8007947 TI - The retinoblastoma gene product RB stimulates Sp1-mediated transcription by liberating Sp1 from a negative regulator. AB - Studies have demonstrated that the retinoblastoma susceptibility gene product, RB, can either positively or negatively regulate expression of several genes through cis-acting elements in a cell-type-dependent manner. The nucleotide sequence of the retinoblastoma control element (RCE) motif, GCCACC or CCACCC, and the Sp1 consensus binding sequence, CCGCCC, can confer equal responsiveness to RB. Here, we report that RB activates transcription of the c-jun gene through the Sp1-binding site within the c-jun promoter. Preincubation of crude nuclear extracts with monoclonal antibodies to RB results in reduction of Sp1 complexes in a mobility shift assay, while addition of recombinant RB in mobility shift assay mixtures with CCL64 cell extracts leads to an enhancement of DNA-binding activity of SP1. These results suggest that RB is directly or indirectly involved in Sp1-DNA binding activity. A mechanism by which RB regulates transactivation is indicated by our detection of a heat-labile and protease-sensitive Sp1 negative regulator(s) (Sp1-I) that specifically inhibits Sp1 binding to a c-jun Sp1 site. This inhibition is reversed by addition of recombinant RB proteins, suggesting that RB stimulates Sp1-mediated transactivation by liberating Sp1 from Sp1-I. Additional evidence for Sp1-I involvement in Sp1-mediated transactivation was demonstrated by cotransfection of RB, GAL4-Sp1, and a GAL4-responsive template into CV-1 cells. Finally, we have identified Sp1-I, a approximately 20-kDa protein(s) that inhibits the Sp1 complexes from binding to DNA and that is also an RB-associated protein. These findings provide evidence for a functional link between two distinct classes of oncoproteins, RB and c-Jun, that are involved in the control of cell growth, and also define a novel mechanism for the regulation of c-jun expression. PMID- 8007948 TI - Cell-specific expression of the macrophage scavenger receptor gene is dependent on PU.1 and a composite AP-1/ets motif. AB - The type I and II scavenger receptors (SRs) are highly restricted to cells of monocyte origin and become maximally expressed during the process of monocyte-to macrophage differentiation. In this report, we present evidence that SR genomic sequences from -245 to +46 bp relative to the major transcriptional start site were sufficient to confer preferential expression of a reporter gene to cells of monocyte and macrophage origin. This profile of expression resulted from the combinatorial actions of multiple positive and negative regulatory elements. Positive transcriptional control was primarily determined by two elements, located 181 and 46 bp upstream of the major transcriptional start site. Transcriptional control via the -181 element was mediated by PU.1/Spi-1, a macrophage and B-cell-specific transcription factor that is a member of the ets domain gene family. Intriguingly, the -181 element represented a relatively low affinity binding site for Spi-B, a closely related member of the ets domain family that has been shown to bind with relatively high affinity to other PU.1/Spi-1 binding sites. These observations support the idea that PU.1/Spi-1 and Spi-B regulate overlapping but nonidentical sets of genes. The -46 element represented a composite binding site for a distinct set of ets domain proteins that were preferentially expressed in monocyte and macrophage cell lines and that formed ternary complexes with members of the AP-1 gene family. In concert, these observations suggest a model for how interactions between cell-specific and more generally expressed transcription factors function to dictate the appropriate temporal and cell-specific patterns of SR expression during the process of macrophage differentiation. PMID- 8007950 TI - Enhancement or inhibition of insulin signaling by insulin receptor substrate 1 is cell context dependent. AB - Insulin treatment of Chinese hamster ovary (CHO) cells expressing high levels of the insulin receptor (CHO/IR cells) activates both c-fos serum response element and activator protein 1 (AP-1) reporter genes approximately 10-fold. In contrast, parental CHO cells display only two- to threefold insulin stimulation of reporter gene activity. Transient transfection of parental CHO cells with an insulin receptor substrate 1 (IRS1) expression plasmid enhanced insulin downstream signaling in a biphasic manner, whereas IRS1 transfection of CHO/IR cells inhibited insulin signaling in a dose-dependent fashion. Further, expression of Grb2 in parental CHO cells had no effect on insulin signaling, whereas Grb2 increased insulin activation of reporter gene expression in CHO/IR cells. These data suggest that the expression levels of various effector molecules can either enhance or inhibit insulin downstream signaling events. To assess the relative effects of various insulin receptor, IRS1, and Grb2 levels on insulin signaling, parental CHO cells were transiently transfected with various combinations of expression plasmids encoding these proteins. Although expression of IRS1 resulted in a biphasic increase of insulin signaling in parental CHO cells, coexpression of IRS1 with the insulin receptor resulted in inhibition of signaling. This inhibition of insulin signaling directly correlated with an increased association of Grb2 with IRS1 and a concomitant sequestration of Grb2 away from Shc. Consistent with the Shc-Grb2 pathway as the major route for insulin-stimulated c Fos and AP-1 transcriptional activation, the IRS1-mediated inhibition was reversed by transfection with an expression plasmid for Grb2. These data demonstrate that the extent of insulin-stimulated downstream signaling was dependent not only on the levels of individual signaling molecules but also on the formation of multiprotein complexes with specific stoichiometries. PMID- 8007949 TI - Protein kinase A acts at multiple points to inhibit Xenopus oocyte maturation. AB - In Xenopus oocytes, initiation of maturation is dependent on reduction of cyclic AMP-dependent protein kinase (PKA) activity and the synthesis of the mos proto oncogene product. Mos is required during meiosis I for the activation of both maturation-promoting factor (MPF) and mitogen-activated protein kinase (MAPK). Here we show that injection of the catalytic subunit of PKA (PKAc) prevented progesterone-induced synthesis of endogenous Mos as well as downstream MPF and MAPK activation. However, PKAc did not prevent injected soluble Mos product from activating MAPK. While MAPK is activated during Mos-PKAc coinjection, attendant MPF activation is blocked. Additionally, PKAc caused a potent block in the electrophoretic mobility shift of cdc25 that is associated with phosphatase activation. This inhibition of cdc25 activity was not reversed by progesterone, Mos, or MPF. We conclude that PKAc acts as a negative regulator at several points in meiotic maturation by preventing both Mos translation and MPF activation. PMID- 8007952 TI - Abnormal deletions in the T-cell receptor delta locus of mouse thymocytes. AB - Separate genetic elements (V, D, and J) encode the variable regions of lymphocyte antigen receptors. During early lymphocyte differentiation, these elements rearrange to form contiguous coding segments (VJ and VDJ) for a diverse array of variable regions. Rearrangement is mediated by a recombinase that recognizes short DNA sequences (signals) flanking V, D, and J elements. Signals flank both the 5' and 3' sides of each D element, thereby allowing assembly of a functional VDJ gene. However, in rearrangements involving the D delta 2 and J delta 1 elements of the mouse T-cell receptor delta (TCR delta) locus, we unexpectedly found that the D delta 2 element and a portion of its 5' signal are often deleted. Approximately 50% of recovered D delta 2 to J delta 1 rearrangements from thymocytes of adult wild-type mice showed such deletions. An additional 20% of the rearrangements contained standard D delta 2-J delta 1 coding junctions but showed some loss of nucleotides from the 5' D delta 2 signal. This loss was clearly associated with another event involving a site-specific cleavage at the 5' signal/coding border of D delta 2 and rejoining of the modified signal and coding ends. The abnormal loss of D delta 2 and a portion of the 5' D delta 2 signal was infrequently observed in D delta 2-to-J delta 1 rearrangements recovered from neonatal mice. The possible basis and significance of this age dependent phenomenon are discussed. PMID- 8007951 TI - Multiple regulatory elements in the interleukin-6 gene mediate induction by prostaglandins, cyclic AMP, and lipopolysaccharide. AB - Induction of interleukin-6 (IL-6) gene expression is mediated by numerous agents involving all major signal transduction pathways. We have compared the effects of prostaglandins and their second messenger cyclic AMP (cAMP) with the effect of lipopolysaccharide (LPS) on IL-6 gene expression. We demonstrate that secretion of IL-6 is induced by cAMP in murine monocytic PU5-1.8 cells, even though to a lesser extent than by LPS. Nevertheless, cAMP and prostaglandins of the E series in the presence of theophylline induce transcription of the IL-6 promoter more strongly than LPS, suggesting distinctive effects of cAMP and LPS on posttranscriptional events. Mutations within four regulatory elements, namely, the multiple response element (MRE), AP-1, NF-IL6, and NF-kappa B sites, significantly reduce, but do not completely abrogate, inducibility by cAMP and prostaglandin E1, whereas alterations of four additional sites have no effects. LPS-induced promoter activity, however, is almost completely abolished by mutations in the NF-kappa B site, suggesting that a single regulatory element is crucial for inducibility by LPS. Stimulation by cAMP is correlated with the binding of inducible factors to the AP-1, NF-IL6, and NF-kappa B elements, whereas factors binding to the MRE are constitutively expressed. Recombinant cAMP response element-binding protein binds to the MRE, indicating a potential role for this factor in the cAMP response. Our results suggest that cAMP and prostaglandins act through multiple, partially redundant regulatory elements to induce IL-6 expression in monocytic cells. Nuclear events that overlap partially with the LPS response but also exhibit distinctive features are involved. PMID- 8007953 TI - The ecdysone response enhancer of the Fbp1 gene of Drosophila melanogaster is a direct target for the EcR/USP nuclear receptor. AB - The transcription of the Drosophila melanogaster Fbp1 gene is induced by the steroid hormone 20-hydroxyecdysone and restricted to the late-third-instar fat body tissue. In a previous study we showed that the -68 to -138 region relative to the transcription start site acts as an ecdysone-dependent third-instar fat body-specific enhancer in a transgenic assay. Here we report that seven nucleoprotein complexes are formed in vitro on this enhancer when a nuclear extract from late-third-instar fat body is used in a gel shift assay. Accurate mapping of the binding sites of the complexes revealed a remarkably symmetrical organization. Using specific antibodies, one of the complexes was identified as a heterodimer consisting of the ecdysone receptor (EcR) and Ultraspiracle (USP) proteins. The binding site of the heterodimer as defined by mutagenesis and methylation interference experiments bears strong sequence similarity to the canonical hsp27 ecdysone response element, including an imperfect palindromic structure. The two elements diverge at three positions in both half-sites, indicating that the structure of an active EcR/USP binding site allows considerable sequence variations. In vivo footprinting experiments using ligation mediated PCR and wild-type or ecdysteroid-deficient larvae show that occupancy of the Fbp1 EcR/USP binding site and adjacent region is dependent on a high concentration of ecdysteroids. These results provide strong evidence for a direct role of the EcR/USP heterodimer in driving gene expression in response to changes of the ecdysteroid titer during Drosophila larval development. PMID- 8007955 TI - Effect of mutations in genes affecting homologous recombination on restriction enzyme-mediated and illegitimate recombination in Saccharomyces cerevisiae. AB - Restriction enzyme-mediated events (REM events; integration of transforming DNA catalyzed by in vivo action of a restriction enzyme) and illegitimate recombination events (IR events; integration of transforming DNA that shares no homology with the host genomic sequences) have been previously characterized in Saccharomyces cerevisiae. This study determines the effect of mutations in genes that are involved in homologous recombination and/or in the repair of double stranded DNA breaks on these recombination events. Surprisingly, REM events are completely independent of the double-strand-break repair functions encoded by the RAD51, RAD52, and RAD57 genes but require the RAD50 gene product. IR events are under different genetic control than homologous integration events. In the rad50 mutant, homologous integration occurred at wild-type frequency, whereas the frequency of IR events was 20- to 100-fold reduced. Conversely, the rad52 mutant was grossly deficient in homologous integration (at least 1,000-fold reduced) but showed only a 2- to 8-fold reduction in IR frequency. PMID- 8007954 TI - Induction of the mouse serum amyloid A3 gene by cytokines requires both C/EBP family proteins and a novel constitutive nuclear factor. AB - Serum amyloid A (SAA) is a major acute-phase protein synthesized and secreted mainly by the liver. In response to acute inflammation, its expression may be induced up to 1,000-fold, primarily as a result of a 200-fold increase in the rate of SAA gene transcription. We have previously demonstrated that a 350-bp promoter fragment from the mouse SAA3 gene was necessary and sufficient to confer liver-specific and cytokine-induced expression. Deletion studies identified a distal response element that is responsible for the cytokine response and has properties of an inducible transcriptional enhancer. In this study, we further analyzed the distal response element and showed that it consists of three functionally distinct elements: the A element constitutes a weak binding site for C/EBP family proteins, the B element also interacts with C/EBP family proteins but with a much higher binding affinity, and the C element interacts with a novel constitutive nuclear factor, SEF-1. Site-specific mutation studies revealed that all three elements were required for maximum promoter activity. C/EBP alpha, C/EBP beta, and C/EBP delta were capable of interacting with elements A and B. Under noninduced conditions, C/EBP alpha was the major binding factor; however, upon cytokine stimulation C/EBP beta- and C/EBP delta-binding activities were dramatically increased and became the predominant binding factors. Consistent with these binding studies were the cotransfection experiments in which C/EBP beta and C/EBP delta were shown to be potent transactivators for the SAA3 promoter. Moreover, the transactivation required an intact B element despite the presence of other functional C/EBP-binding sites. Interestingly, although element C did not interact with C/EBP directly, it was nevertheless required for maximum transactivation by C/EBP delta. Our studies thus demonstrate that both C/EBP family proteins and SEF-1 are required to transactivate the SAA3 gene. PMID- 8007956 TI - sir2 mutants of Kluyveromyces lactis are hypersensitive to DNA-targeting drugs. AB - A Kluyveromyces lactis mutant, hypersensitive to the DNA-targeting drugs ethidium bromide (EtBr), berenil, and HOE15030, can be complemented by a wild-type gene with homology to SIR2 of Saccharomyces cerevisiae (ScSIR2). The deduced amino acid sequence of the K. lactis Sir2 protein has 53% identity with ScSir2 protein but is 108 residues longer. K. lactis sir2 mutants show decreased mating efficiency, deficiency in sporulation, an increase in recombination at the ribosomal DNA locus, and EtBr-induced death. Some functional equivalence between the Sir2 proteins of K. lactis and S. cerevisiae has been demonstrated by introduction of ScSIR2 into a sir2 mutant of K. lactis. Expression of ScSIR2 on a multicopy plasmid restores resistance to EtBr and complements sporulation deficiency. Similarly, mating efficiency of a sir2 mutant of S. cerevisiae is partially restored by K. lactis SIR2 on a multicopy plasmid. Although these observations suggest that there has been some conservation of Sir2 protein function, a striking difference is that sir2 mutants of S. cerevisiae, unlike their K. lactis counterparts, are not hypersensitive to DNA-targeting drugs. PMID- 8007957 TI - CCR4 is a glucose-regulated transcription factor whose leucine-rich repeat binds several proteins important for placing CCR4 in its proper promoter context. AB - The yeast CCR4 protein is required for the expression of a number of genes involved in nonfermentative growth, including glucose-repressible ADH2, and is the only known suppressor of mutations in the SPT6 and SPT10 genes, two genes which are believed to be involved in chromatin maintenance. We show here that although CCR4 did not bind DNA under the conditions tested, it was able to activate transcription when fused to a heterologous DNA-binding domain. The transcriptional activation ability of CCR4, in contrast to that of many other activators, was glucose regulated. Two activation domains one of which was glucose responsive and encompassed a glutamine-proline-rich region similar to that found in other eukaryotic transcriptional factors were identified. The two transactivation regions, when separated from the leucine-rich repeat and the C terminus of CCR4, were unable to complement a defective ccr4 allele, suggesting that the leucine-rich repeat and the C terminus make contacts that link the activation regions to the proper gene context. Native immunoprecipitation of CCR4 revealed that CCR4 was complexed with at least four other proteins. The leucine rich repeat of CCR4 was both necessary and sufficient for interaction with at least two of these factors. We propose that the leucine-rich repeat links CCR4 through its associated factors to its promoter context at ADH2 and other loci where it is required for proper transcriptional regulation. PMID- 8007959 TI - Unique catalytic properties dictate the enhanced function of p59fynT, the hemopoietic cell-specific isoform of the Fyn tyrosine protein kinase, in T cells. AB - As a result of alternative splicing, the fyn gene encodes two different tyrosine protein kinase isoforms. While one protein (p59fynB) is abundantly expressed in the brain, the alternative product (p59fynT) is contained only in cells of hemopoietic lineages, especially T lymphocytes. Sequence analyses have revealed that these two isoforms differ exclusively within a stretch of 52 amino acids which overlaps the end of the Src homology 2 (SH2) motif and the beginning of the catalytic domain. Consistent with the idea that FynT provides a specialized function in hemopoietic cells, we have previously shown that expression of activated FynT molecules, but not that of activated FynB polypeptides, enhanced the antigen responsiveness of a mouse T-cell line (BI-141) (D. Davidson, L. M. L. Chow, M. Fournel, and A. Veillette, J. Exp. Med. 175:1483-1492, 1992). In this study, we examined the basis for the distinct signalling capabilities of the two Fyn isoforms in T lymphocytes. Our biochemical analyses revealed that FynT is more adept than FynB at promoting antigen receptor-triggered calcium fluxes. This phenomenon likely contributes to the improved biological function of FynT during antigen stimulation, as the calcium ionophore ionomycin partially rescued the inability of FynB to enhance antigen-induced lymphokine secretion. To establish the structural basis for these observations, we also created and analyzed a series of chimeras of FynT and FynB. These studies demonstrated that the distinct catalytic domain of FynT, and not its altered SH2 motif, is responsible for the improved ability to augment antigen responsiveness. Similarly, this sequence enhances the ability to mobilize cytosolic calcium in response to antigen receptor stimulation. Taken together, these data show that the distinct biological impacts of FynT and FynB in T cells are related to limited structural differences in the amino-terminal portion of their catalytic domains and that they reflect, at least in part, the greater ability of FynT to mobilize cytoplasmic calcium. PMID- 8007960 TI - trans-spliceosomal U6 RNAs of Crithidia fasciculata and Leptomonas seymouri: deviation from the conserved ACAGAG sequence and potential base pairing with spliced leader RNA. AB - U6 RNA genes from the trypanosomatids Crithidia fasciculata and Leptomonas seymouri have been isolated and sequenced. As in Trypanosoma brucei, the U6 RNA genes in both C. fasciculata and L. seymouri are arranged in close linkage with upstream tRNA genes. The U6 RNA sequences from C. fasciculata and L. seymouri deviate in five and three positions, respectively, from the published T. brucei sequence. Interestingly, both C. fasciculata U6 RNA genes carry a C-->T change at the second position of the ACAGAG hexanucleotide sequence, which is important for splicing function and has been considered phylogenetically invariable. A compensatory base change of the C. fasciculata spliced leader RNA at the highly conserved 5' splice site position +5, G-->A, suggests that an interaction between the 5' splice site region and U6 RNA recently proposed for the yeast cis-splicing system may also occur in trans splicing. PMID- 8007958 TI - Expression of mutant eukaryotic initiation factor 2 alpha subunit (eIF-2 alpha) reduces inhibition of guanine nucleotide exchange activity of eIF-2B mediated by eIF-2 alpha phosphorylation. AB - The inhibition of protein synthesis that occurs upon phosphorylation of the alpha subunit of eukaryotic initiation factor 2 (eIF-2 alpha) at serine 51 correlates with reduced guanine nucleotide exchange activity of eIF-2B in vivo and inhibition of eIF-2B activity in vitro, although it is not known if phosphorylation is the cause of the reduced eIF-2B activity in vivo. To characterize the importance of eIF-2 alpha phosphorylation in the regulation of eIF-2B activity, we studied the overexpression of mutant eIF-2 alpha subunits in which serine 48 or 51 was replaced by an alanine (48A or 51A mutant). Previous studies demonstrated that the 51A mutant was resistant to phosphorylation, whereas the 48A mutant was a substrate for phosphorylation. Additionally, expression of either mutant partially protected Chinese hamster ovary (CHO) cells from the inhibition of protein synthesis in response to heat shock treatment (P. Murtha-Riel, M. V. Davies, J. B. Scherer, S. Y. Choi, J. W. B. Hershey, and R. J. Kaufman, J. Biol. Chem. 268:12946-12951, 1993). In this study, we show that eIF 2B activity was inhibited in parental CHO cell extracts upon addition of purified reticulocyte heme-regulated inhibitor (HRI), an eIF-2 alpha kinase that phosphorylates Ser-51. Preincubation with purified HRI also reduced the eIF-2B activity in extracts from cells overexpressing wild-type eIF-2 alpha. In contrast, the eIF-2B activity was not readily inhibited in extracts from cells overexpressing either the eIF-2 alpha 48A or 51A mutant. In addition, eIF-2B activity was decreased in extracts prepared from heat-shocked cells overexpressing wild-type eIF-2 alpha, whereas the decrease in eIF-2B activity was less in heat-shocked cells overexpressing either mutant 48A or mutant 51A. While the phosphorylation at serine 51 in eIF-2 alpha impairs the eIF-2B activity, we propose that serine 48 acts to maintain a high affinity between phosphorylated eIF-2 alpha and eIF-2B, thereby inactivating eIF-2B activity. These findings support the hypothesis that phosphorylation of eIF-2 alpha inhibits protein synthesis directly through reducing eIF-2B activity and emphasize the importance of both serine 48 and serine 51 in the interaction with eIF-2B and regulation of eIF-2B activity. PMID- 8007961 TI - Biochemical and genetic analysis of dominant-negative mutations affecting a yeast G-protein gamma subunit. AB - Heterotrimeric guanine nucleotide-binding proteins (G proteins) consisting of alpha, beta, and gamma subunits mediate signalling between cell surface receptors and intracellular effectors in eukaryotic cells. To define signalling functions of G gamma subunits (STE18 gene product) involved in pheromone response and mating in the yeast Saccharomyces cerevisiae, we isolated and characterized dominant-negative STE18 alleles. We obtained dominant-negative mutations that disrupt C-terminal sequences required for prenylation of G gamma precursors (CAAX box) and that affect residues in the N-terminal half of Ste18p. Overexpression of mutant G gamma subunits in wild-type cells blocked signal transduction; this effect was suppressed upon overexpression of G beta subunits. Mutant G gamma subunits may therefore sequester G beta subunits into nonproductive G beta gamma dimers. Because mutant G gamma subunits blocked the constitutive signal resulting from disruption of the G alpha subunit gene (GPA1), they are defective in functions required for downstream signalling. Ste18p bearing a C107Y substitution in the CAAX box displayed reduced electrophoretic mobility, consistent with a prenylation defect. G gamma subunits carrying N-terminal substitutions had normal electrophoretic mobilities, suggesting that these proteins were prenylated. G gamma subunits bearing substitutions in their N-terminal region or C-terminal CAAX box (C107Y) supported receptor-G protein coupling in vitro, whereas C terminal truncations caused partial defects in receptor coupling. PMID- 8007962 TI - Dual modes of control of c-fos mRNA induction by intracellular calcium in T cells. AB - Cytoplasmic calcium is a nearly universal second messenger in eukaryotes. In many cell types, elevated intracellular calcium interacts synergistically with inducers of protein kinase C to elicit activation of complete biological programs normally induced by extracellular signals. In T cells, elevated cytoplasmic calcium is a critical mediator of activation in response to stimulation of the antigen receptor, and in some T-cell lines, treatment with a combination of calcium ionophore and protein kinase C activator mimics authentic antigen treatment. The synergistic interaction of calcium and protein kinase C in T cells is also observed at the level of gene expression. Here we examine the molecular mechanisms through which these agents exert synergistic control over the expression of the c-fos proto-oncogene in a T-cell hybridoma. We find that the principal effect of calcium is on the elongation of c-fos transcripts. This step constitutes the major control of c-fos mRNA accumulation in these cells. In addition, calcium regulates the initiation of c-fos transcription. This effect requires the serum response element of the c-fos gene and an additional sequence immediately 3' to this element. Thus, calcium regulates c-fos expression through at least two distinct molecular pathways. PMID- 8007963 TI - A functional insulin-like growth factor I receptor is required for the mitogenic and transforming activities of the epidermal growth factor receptor. AB - When wild-type mouse embryo cells are stably transfected with a plasmid constitutively overexpressing the epidermal growth factor (EGF) receptor (EGFR), the resulting cells can grow in serum-free medium supplemented solely with EGF. Supplementation with EGF also induces in these cells the transformed phenotype (growth in soft agar). However, when the same EGFR expression plasmid is introduced and overexpressed in cells derived from littermate embryos in which the insulin-like growth factor I (IGF-I) receptor genes have been disrupted by homologous recombination, the resulting cells are unable to grow or to be transformed by the addition of EGF. Reintroduction into these cells (null for the IGF-I receptor) of a wild-type (but not of a mutant) IGF-I receptor restores EGF mediated growth and transformation. Our results indicate that at least in mouse embryo fibroblasts, the EGFR requires the presence of a functional IGF-I receptor for its mitogenic and transforming activities. PMID- 8007964 TI - Myocyte nuclear factor, a novel winged-helix transcription factor under both developmental and neural regulation in striated myocytes. AB - A sequence motif (CCAC box) within an upstream enhancer region of the human myoglobin gene is essential for transcriptional activity in both cardiac and skeletal muscle. A cDNA clone, myocyte nuclear factor (MNF), was isolated from a murine expression library on the basis of sequence-specific binding to the myoglobin CCAC box motif and was found to encode a novel member of the winged helix or HNF-3/fork head family of transcription factors. Probes based on this sequence identify two mRNA species that are upregulated during myocyte differentiation, and antibodies raised against recombinant MNF identify proteins of approximately 90, 68, and 65 kDa whose expression is regulated following differentiation of myogenic cells in culture. In addition, the 90-kDa form of MNF is phosphorylated and is upregulated in intact muscles subjected to chronic motor nerve stimulation, a potent stimulus to myoglobin gene regulation. Amino acid residues 280 to 389 of MNF demonstrate 35 to 89% sequence identity to the winged helix domain from other known members of this family, but MNF is otherwise divergent. A proline-rich amino-terminal region (residues 1 to 206) of MNF functions as a transcriptional activation domain. These studies provide the first evidence that members of the winged-helix family of transcription factors have a role in myogenic differentiation and in remodeling processes of adult muscles that occur in response to physiological stimuli. PMID- 8007965 TI - Functional specificity of cytoplasmic and transmembrane tyrosine kinases: identification of 130- and 75-kilodalton substrates of c-fps/fes tyrosine kinase in macrophages. AB - c-fps/fes encodes a 92-kDa protein-tyrosine kinase (NCP92) that is expressed at the highest levels in macrophages. To determine if c-fps/fes can mediate the action of the colony-stimulating factor 1 (CSF-1) receptor (CSF-1R) and to identify potential targets of c-fps/fes in macrophages, we have overexpressed c fps/fes in a CSF-1-dependent macrophage cell line. A 30- to 50-fold overexpression of c-fps/fes partially released these cells from their factor dependence by a nonautocrine mechanism, and this correlated with the tyrosine phosphorylation of two proteins of 130 and 75 kDa (P130 and P75). c-fps/fes did not cause tyrosine phosphorylation or activation of CSF-1 dependent targets, including CSF-1R, Shc, and phosphatidylinositol 3-kinase, and conversely, CSF-1 did not induce tyrosine phosphorylation of P130 and P75. P75 appears to be a novel phosphotyrosyl protein, whereas P130 cross-reacts with a known substrate of v-src. P130 and P75 may be direct substrates of c-fps/fes: P130 was tightly associated with NCP92, and the src homology 2 domain of NCP92 specifically bound phosphorylated P130 and P75 but not the CSF-1-induced phosphotyrosyl proteins, consistent with the possibility that P130 and P75 are physiological targets of c fps/fes. We conclude that although c-fps/fes can functionally substitute for CSF 1R to a certain extent, these tyrosine kinases act largely independently of each other and that P130 and P75 are novel targets whose mechanisms of action may be unrelated to the signalling pathways utilized by receptor tyrosine kinases. PMID- 8007966 TI - Different oligomeric forms of protein phosphatase 2A activate and inhibit simian virus 40 DNA replication. AB - The ability of simian virus 40 (SV40) large T antigen to catalyze the initiation of viral DNA replication is regulated by its phosphorylation state. Previous studies have identified the free catalytic subunit of protein phosphatase 2A (PP2Ac) as the cellular phosphatase which can remove inhibitory phosphoryl groups from serines 120 and 123. The catalytic C subunit exists in the cell complexed with a 65-kDa A subunit and one of several B subunits. To determine if any of the holoenzymes could activate T antigen, we tested the ability of the heterodimeric AC and two heterotrimeric ABC forms to stimulate T-antigen function in unwinding the origin of SV40 DNA replication. Only free catalytic subunit C and the heterotrimeric form with a 72-kDa B subunit (PP2A-T72) could stimulate T-antigen dependent origin unwinding. Both the dimeric form (PP2A-D) and the heterotrimer with a 55-kDa B subunit (PP2A-T55) actively inhibited T-antigen function. We found that PP2A-T72 activated T antigen by dephosphorylating serines 120 and 123, while PP2A-D and PP2A-T55 inactivated T antigen by dephosphorylating the p34cdc2 target site, threonine 124. Thus, alterations in the subunit composition of PP2A holoenzymes have significant functional consequences for the initiation of in vitro SV40 DNA replication. The regulatory B subunits of PP2A may play a role in regulating SV40 DNA replication in infected cells as well. PMID- 8007967 TI - Single-stranded-DNA-binding protein-dependent DNA unwinding of the yeast ARS1 region. AB - DNA unwinding of autonomously replicating sequence 1 (ARS1) from the yeast Saccharomyces cerevisiae was investigated. When a negatively supercoiled plasmid DNA containing ARS1 was digested with single-strand-specific mung bean nuclease, a discrete region in the vector DNA was preferentially digested. The regions containing the core consensus A domain and the 3'-flanking B domain of ARS1 were weakly digested. When the DNA was incubated with the multisubunit single-stranded DNA-binding protein (SSB, also called RPA [replication protein A]) from human and yeast cells prior to mung bean nuclease digestion, the cleavage in the A and B domains was greatly increased. Furthermore, a region corresponding to the 5' flanking C domain of ARS1 was digested. These results indicate that three domains of ARS1, each of which is important for replication in yeast cells, closely correspond to the regions where the DNA duplex is easily unwound by torsional stress. SSB may stimulate the unwinding of the ARS1 region by its preferential binding to the destabilized three domains. Mung bean nuclease digestion of the substitution mutants with mutations of ARS1 (Y. Marahrens and B. Stillman, Science 255:817-823, 1992) revealed that the sequences in the B2 and A elements are responsible for the unwinding of the B domain and the region containing the A domain, respectively. PMID- 8007968 TI - T7 RNA polymerase-dependent expression of COXII in yeast mitochondria. AB - An in vivo expression system has been developed for controlling the transcription of individual genes in the mitochondrial genome of Saccharomyces cerevisiae. The bacteriophage T7 RNA polymerase (T7Pol), fused to the COXIV mitchondrial import peptide and expressed under the control of either the GAL1 or the ADH1 promoter, efficiently transcribes a target gene, T7-COX2, in the mitochondrial genome. Cells bearing the T7-COX2 gene, but lacking wild-type COX2, require T7Pol for respiration. Functional expression of T7-COX2 is completely dependent on the COX2 specific translational activator Pet111p, despite additional nucleotides at the 5' end of the T7-COX2 transcript. Expression of mitochondrion-targeted T7Pol at high levels from the GAL1 promoter has no detectable effect on mitochondrial function in rho+ cells lacking the T7-COX2 target gene, but in cells with T7-COX2 integrated into the mitochondrial genome, an equivalent level of T7Pol expression causes severe respiratory deficiency. In comparison with wild-type COX2 expression, steady-state levels of T7-COX2 mRNA increase fivefold when transcription is driven by T7Pol expressed from the ADH1 promoter, yet COXII protein levels and cellular respiration rates decrease by about 50%. This discoordinate expression of mRNA and protein provides additional evidence for posttranscriptional control of COX2 expression. PMID- 8007970 TI - The Saccharomyces cerevisiae mutation elm4-1 facilitates pseudohyphal differentiation and interacts with a deficiency in phosphoribosylpyrophosphate synthase activity to cause constitutive pseudohyphal growth. AB - Saccharomyces cerevisiae mutant E124 was selected in a visual screen based on elongated cell shape. Genetic analysis showed that E124 contains two separate mutations, pps1-1 and elm4-1, each causing a distinct phenotype inherited as a single-gene trait. In rich medium, pps1-1 by itself causes increased doubling time but does not affect cell shape, whereas elm4-1 results in a moderate cell elongation phenotype but does not affect growth rate. Reconstructed elm4-1 pps1-1 double mutants display a synthetic phenotype in rich medium including extreme cell elongation and delayed cell separation, both characteristics of pseudohyphal differentiation. The elm4-1 mutation was shown to act as a dominant factor that potentiates pseudohyphal differentiation in response to general nitrogen starvation in a genetic background in which pseudohyphal growth normally does not occur. Thus, elm4-1 allows recognition of, or response to, a pseudohyphal differentiation signal that results from nitrogen limitation. PPS1 was isolated and shown to be a previously undescribed gene coding for a protein similar in amino acid sequence to phosphoribosylpyrophosphate synthase, a rate-limiting enzyme in the biosynthesis of nucleotides, histidine, and tryptophan. Thus, the pps1-1 mutation may generate a nitrogen limitation signal, which when coupled with elm4-1 results in pseudohyphal growth even in rich medium. PMID- 8007969 TI - Transcriptional control of the yeast PDR5 gene by the PDR3 gene product. AB - Saccharomyces cerevisiae cells possess the ability to simultaneously acquire resistance to an array of drugs with different cytotoxic activities. The genes involved in this acquisition are referred to as pleiotropic drug resistant (PDR) genes. Several semidominant, drug resistance-encoding PDR mutations have been found that map near the centromere on chromosome II, including PDR3-1 and PDR4-1. DNA sequencing of chromosome II identified a potential open reading frame, designated YBL03-23, that has the potential to encode a protein with strong sequence similarity to the product of the PDR1 gene, a zinc finger-containing transcription factor. Here we show that YBL03-23 is allelic with PDR3. The presence of a functional copy of either PDR1 or PDR3 is essential for drug resistance and expression of a putative membrane transporter-encoding gene, PDR5. Deletion mapping of the PDR5 promoter identified a region from -360 to -112 that is essential for expression of this gene. DNase I footprinting analysis using bacterially expressed Pdr3p showed specific recognition by this protein of at least one site in the -360/-112 interval in the PDR5 promoter. A high-copy-number plasmid carrying the PDR3 gene elevated resistance to both oligomycin and cycloheximide. Increasing the number of PDR3 gene copies in a delta pdr5 strain increased oligomycin resistance but was not able to correct the cycloheximide hypersensitivity that results from loss of PDR5. These data are consistent with the notion that PDR3 acts to increase cycloheximide resistance by elevating the level of PDR5 transcription, while PDR3-mediated oligomycin resistance acts through some other target gene. PMID- 8007971 TI - Scaffold attachment regions stimulate HSP70.1 expression in mouse preimplantation embryos but not in differentiated tissues. AB - Eukaryotic interphase chromatin is thought to be organized into topologically discrete, independent domains acting as units upon which differential patterns of gene expression are established. Sequences which attach chromatin to in vitro preparations of a nucleoprotein matrix (scaffold attachment regions [SARs]) may act as domain boundaries, but their role remains poorly defined compared with those of other elements such as locus control regions. We have produced mice homozygous for a transgene which is transcribed as early as the activation of the embryonic genome at the two-cell stage and which is expressed ubiquitously in a number of differentiated tissues. Transgenic lines were generated in the presence or absence of flanking SAR sequences, creating an original model which enabled us to examine the effects of these elements at different developmental stages. In the preimplantation mouse embryo, flanking SARs stimulated transgene expression in a copy-dependent manner. In contrast, in the differentiated tissues of newborn and adult mice, no significant SAR-dependent increase in transgene expression was found, correlation with copy number was lost, and position effects were observed. These results suggest a limited capacity of SARs to act as insulating elements but are consistent with a proposed model of SAR-mediated chromatin opening and closing. PMID- 8007972 TI - Role of maturation-promoting factor (p34cdc2-cyclin B) in differential expression of the Xenopus oocyte and somatic-type 5S RNA genes. AB - Transcription of 5S rRNA and tRNA genes by RNA polymerase III (pol III) in cytosolic extracts of unfertilized Xenopus eggs and in a reconstituted system derived from Xenopus oocytes is repressed by the action of one or more mitotic protein kinases. Repression is due to the phosphorylation of a component of the pol III transcription apparatus. We find that the maturation/mitosis-promoting factor kinase (MPF, p34cdc2-cyclin B) can directly mediate this repression in vitro. Affinity-purified MPF and immune complexes formed with antibodies to the protein subunits of MPF (p34cdc2 and cyclin B) retain both histone H1 kinase activity and the capacity to repress transcription in the reconstituted transcription system. Transcription complexes of oocyte-type 5S RNA genes and tRNA genes are quantitatively more sensitive to MPF repression than the corresponding transcription complexes of the somatic-type 5S RNA gene. The differential transcription of oocyte- and somatic-type genes observed during early Xenopus embryogenesis has been reproduced with the reconstituted transcription system and affinity-purified MPF. This differential transcription may be due to the instability of transcription complexes on the oocyte-type genes and the heightened sensitivity of soluble transcription factors to inactivation by mitotic phosphorylation. Our results suggest that MPF may play a role in vivo in the establishment of the embryonic pattern of pol III gene expression. PMID- 8007973 TI - Repression of basal transcription by HMG2 is counteracted by TFIIH-associated factors in an ATP-dependent process. AB - A basal repressor of class II gene transcription was identified, purified, and found to be identical to nonhistone chromosomal protein HMG2. HMG2 was shown to inhibit basal transcription under conditions in which transcription templates form soluble complexes with HMG2. Order-of-addition experiments clearly revealed that HMG2 acted after assembly of a TBP-TFIIA-promoter complex and before formation of the fourth phosphodiester bond by RNA polymerase II. Subsequently, an activity that efficiently counteracted repression of transcription by HMG2 in both TBP- and TFIID-containing transcription systems was isolated. Several lines of evidence suggested that antirepression was mediated by a TFIIH-associated factor. The antirepressor first coeluted with TFIIH, was depleted from this fraction by antibodies directed against the TFIIH subunit p62, was dependent on either ATP or dATP, and then was inhibited by the ATP analogs AMP-PNP and ATP gamma S. Relief of HMG2-mediated repression as well as basal promoter function of TFIIH may involve a helicase that coelutes with TFIIH and displays similar nucleotide specificities. Taken together, these data suggest novel consequences of chromatin-associated HMG proteins and they provide direct evidence for a role of TFIIH-associated enzymes in ATP-dependent antirepression of nonhistone chromosomal proteins. PMID- 8007974 TI - N-terminally myristoylated Ras proteins require palmitoylation or a polybasic domain for plasma membrane localization. AB - Plasma membrane targeting of Ras requires CAAX motif modifications together with a second signal from an adjacent polybasic domain or nearby cysteine palmitoylation sites. N-terminal myristoylation is known to restore membrane binding to H-ras C186S (C-186 is changed to S), a mutant protein in which all CAAX processing is abolished. We show here that myristoylated H-ras C186S is a substrate for palmitoyltransferase, despite the absence of C-terminal farnesylation, and that palmitoylation is absolutely required for plasma membrane targeting of myristoylated H-ras. Similarly, the polybasic domain is required for specific plasma membrane targeting of myristoylated K-ras. In contrast, the combination of myristoylation plus farnesylation results in the mislocalization of Ras to numerous intracellular membranes. Ras that is only myristoylated does not bind with a high affinity to any membrane. The specific targeting of Ras to the plasma membrane is therefore critically dependent on signals that are contained in the hypervariable domain but can be supported by N-terminal myristoylation or C-terminal prenylation. Interestingly, oncogenic Ras G12V that is localized correctly to the plasma membrane leads to mitogen-activated protein kinase activation irrespective of the combination of targeting signals used for localization, whereas Ras G12V that is mislocalized to the cytosol or to other membranes activates mitogen-activated protein kinase only if the Ras protein is farnesylated. PMID- 8007976 TI - The single translation product of the FUM1 gene (fumarase) is processed in mitochondria before being distributed between the cytosol and mitochondria in Saccharomyces cerevisiae. AB - The yeast mitochondrial and cytosolic isoenzymes of fumarase, which are encoded by a single nuclear gene (FUM1), follow a unique mechanism of protein subcellular localization and distribution. Translation of all FUM1 messages initiates only from the 5'-proximal AUG codon and results in a single translation product that contains the targeting sequence located within the first 32 amino acids of the precursor. All fumarase molecules synthesized in the cell are processed by the mitochondrial matrix signal peptidase; nevertheless, most of the enzyme (80 to 90%) ends up in the cytosol. The translocation and processing of fumarase are cotranslational. We suggest that in Saccharomyces cerevisiae, the single type of initial translation product of the FUM1 gene is first partially translocated, and then a subset of these molecules continues to be fully translocated into the organelle, whereas the rest are folded into an import-incompetent state and are released by the retrograde movement of fumarase into the cytosol. PMID- 8007977 TI - Role of Swi4 in cell cycle regulation of CLN2 expression. AB - Expression of the Saccharomyces cerevisiae CLN1 and CLN2 genes is cell cycle regulated, and the genes may be controlled by positive feedback. It has been proposed that positive feedback operates via Cln/Cdc28 activation of the Swi4/Swi6 transcription factor, leading to CLN1 and CLN2 transcription due to Swi4 binding to specific sites (SCBs) in the CLN1 and CLN2 promoters. To test this proposal, we have examined the effects of deletion either of the potential SCBs in the CLN2 promoter or of the SWI4 gene on CLN2 transcriptional control. Deletion of a restriction fragment containing the identified SCBs from the promoter does not prevent cell cycle regulation of CLN2 expression, although expression is lowered at all cell cycle positions. A promoter containing a 5.5-kb plasmid insertion or an independent 2.5-kb insertion at the point of deletion of the SCB-containing restriction fragment also exhibits cell cycle regulation, so involvement of unidentified upstream SCBs is unlikely. Neither Swi4 nor the related Mbp1 transcription factor is required for cell cycle regulation of the intact CLN2 promoter. In contrast, Swi4 (but not Mbp1) is required for correct cell cycle regulation of the insertion/deletion promoter lacking SCB sites. We have extended previous genetic evidence for involvement of Swi4 in some aspect of CLN2 function: a mutant hunt for CLN2 positive regulatory factors yielded only swi4 mutations at saturation. Swi4 may bind to nonconsensus sequences in the CLN2 promoter (possibly in addition to consensus sites), or it may act indirectly to regulate CLN2 expression. PMID- 8007975 TI - Type 1 protein phosphatase acts in opposition to IpL1 protein kinase in regulating yeast chromosome segregation. AB - The IPL1 gene is required for high-fidelity chromosome segregation in the budding yeast Saccharomyces cerevisiae. Conditional ipl1ts mutants missegregate chromosomes severely at 37 degrees C. Here, we report that IPL1 encodes an essential putative protein kinase whose function is required during the later part of each cell cycle. At 26 degrees C, the permissive growth temperature, ipl1 mutant cells are defective in the recovery from a transient G2/M-phase arrest caused by the antimicrotubule drug nocodazole. In an effort to identify additional gene products that participate with the Ipl1 protein kinase in regulating chromosome segregation in yeast, a truncated version of the previously identified DIS2S1/GLC7 gene was isolated as a dosage-dependent suppressor of ipl1ts mutations. DIS2S1/GLC7 is predicted to encode a catalytic subunit (PP1C) of type 1 protein phosphatase. Overexpression of the full-length DIS2S1/GLC7 gene results in chromosome missegregation in wild-type cells and exacerbates the mutant phenotype in ipl1 cells. In addition, the glc7-1 mutation can partially suppress the ipl1-1 mutation. These results suggest that type 1 protein phosphatase acts in opposition to the Ipl1 protein kinase in vivo to ensure the high fidelity of chromosome segregation. PMID- 8007978 TI - Cell cycle-dependent transcription of CLN2 is conferred by multiple distinct cis acting regulatory elements. AB - The budding yeast Saccharomyces cerevisiae CLN1, CLN2, and CLN3 genes encode functionally redundant G1 cyclins required for cell cycle initiation. CLN1 and CLN2 mRNAs accumulate periodically throughout the cell cycle, peaking in late G1. We show that cell cycle-dependent fluctuation in CLN2 mRNA is regulated at the level of transcriptional initiation. Mutational analysis of the CLN2 promoter revealed that the major cell cycle-dependent upstream activating sequence (UAS) resides within a 100-bp fragment. This UAS contains three putative SWI4-dependent cell cycle boxes (SCBs) and two putative MluI cell cycle boxes (MCBs). Mutational inactivation of these elements substantially decreased CLN2 promoter activity but failed to eliminate periodic transcription. Similarly, inactivation of SWI4 decreased CLN2 transcription without affecting its periodicity. We have identified a second UAS in the CLN2 upstream region that can promote cell cycle dependent transcription with kinetics similar to that of the intact CLN2 promoter. Unlike the major CLN2 UAS, this newly identified UAS promotes transcription in cells arrested in G1 by inactivation of cdc28. This novel UAS is both necessary and sufficient for regulated transcription driven by a CLN2 promoter lacking functional SCBs and MCBs. Although this UAS itself contains no SCBs or MCBs, its activity is dependent upon SWI4 function. The characteristics of this novel UAS suggest that it might have a role in initiating CLN2 expression early in G1 to activate the positive feedback loop that drives maximal Cln accumulation. PMID- 8007979 TI - Induction of recombination between homologous and diverged DNAs by double-strand gaps and breaks and role of mismatch repair. AB - Sequence homology is expected to influence recombination. To further understand mechanisms of recombination and the impact of reduced homology, we examined recombination during transformation between plasmid-borne DNA flanking a double strand break (DSB) or gap and its chromosomal homolog. Previous reports have concentrated on spontaneous recombination or initiation by undefined lesions. Sequence divergence of approximately 16% reduced transformation frequencies by at least 10-fold. Gene conversion patterns associated with double-strand gap repair of episomal plasmids or with plasmid integration were analyzed by restriction endonuclease mapping and DNA sequencing. For episomal plasmids carrying homeologous DNA, at least one input end was always preserved beyond 10 bp, whereas for plasmids carrying homologous DNA, both input ends were converted beyond 80 bp in 60% of the transformants. The system allowed the recovery of transformants carrying mixtures of recombinant molecules that might arise if heteroduplex DNA--a presumed recombination intermediate--escapes mismatch repair. Gene conversion involving homologous DNAs frequently involved DNA mismatch repair, directed to a broken strand. A mutation in the PMS1 mismatch repair gene significantly increased the fraction of transformants carrying a mixture of plasmids for homologous DNAs, indicating that PMS1 can participate in DSB initiated recombination. Since nearly all transformants involving homeologous DNAs carried a single recombinant plasmid in both Pms+ and Pms- strains, stable heteroduplex DNA appears less likely than for homologous DNAs. Regardless of homology, gene conversion does not appear to occur by nucleolytic expansion of a DSB to a gap prior to recombination. The results with homeologous DNAs are consistent with a recombinational repair model that we propose does not require the formation of stable heteroduplex DNA but instead involves other homology dependent interactions that allow recombination-dependent DNA synthesis. PMID- 8007981 TI - A pathway for cell wall anchorage of Saccharomyces cerevisiae alpha-agglutinin. AB - Saccharomyces cerevisiae alpha-agglutinin is a cell wall-anchored adhesion glycoprotein. The previously identified 140-kDa form, which contains a glycosyl phosphatidylinositol (GPI) anchor (D. Wojciechowicz, C.-F. Lu, J. Kurjan, and P. N. Lipke, Mol. Cell. Biol. 13:2554-2563, 1993), and additional forms of 80, 150, 250 to 300, and > 300 kDa had the properties of intermediates in a transport and cell wall anchorage pathway. N glycosylation and additional modifications resulted in successive increases in size during transport. The 150- and 250- to 300-kDa forms were membrane associated and are likely to be intermediates between the 140-kDa form and a cell surface GPI-anchored form of > 300 kDa. A soluble form of > 300 kDa that lacked the GPI anchor had properties of a periplasmic intermediate between the plasma membrane form and the > 300-kDa cell wall anchored form. These results constitute experimental support for the hypothesis that GPI anchors act to localize alpha-agglutinin to the plasma membrane and that cell wall anchorage involves release from the GPI anchor to produce a periplasmic intermediate followed by linkage to the cell wall. PMID- 8007980 TI - Inhibition of v-raf-dependent c-fos expression and transformation by a kinase defective mutant of the mitogen-activated protein kinase Erk2. AB - Receptor-bound growth factors elicit intracellular signals that lead to the phosphorylation and activation of numerous intracellular kinases and transcription factors with consequent changes in patterns of gene expression. Several oncogene products are able to mimic these signals, resulting in cell transformation and proliferation. For example, the introduction of oncogenic forms of Raf-1 kinase into fibroblasts induces transformation and leads to the constitutive expression of, among others, the c-fos proto-oncogene. Here it is shown that the elevation of c-fos promoter activity brought about by v-raf is mediated by TCF/Elk-1, which forms a ternary complex with SRF at the serum response element and is a substrate for mitogen-activating protein kinases in vitro. In NIH 3T3 fibroblasts, v-raf activates Erk2, and overexpression of an interfering mutant of Erk2 both blocks the ability of v-raf to activate the c-fos promoter and suppresses transformation. Mutation of individual mitogen-activating protein kinase phosphoacceptor sites in TCF/Elk-1 also compromises v-raf activated expression of a Gal-Elk/Gal-chloramphenicol acetyltransferase reporter system. However, in at least one instance the introduction of glutamate, but not aspartate, at a phosphoacceptor site is compatible with activation. These results provide compelling evidence that phosphorylation of TCF/Elk-1 by Erk2 is a major link in the Raf-1 kinase-dependent signal transduction pathway that activates c fos expression. PMID- 8007982 TI - Murine pluripotent hematopoietic progenitors constitutively expressing a normal erythropoietin receptor proliferate in response to erythropoietin without preferential erythroid cell differentiation. AB - Erythropoietin (EPO) is a prime regulator of the growth and differentiation of erythroid blood cells. The EPO receptor (EPO-R) is expressed in late erythroid progenitors (mature BFU-E and CFU-E), and EPO induces proliferation and differentiation of these cells. By introducing, with a retroviral vector, a normal EPO-R cDNA into murine adult bone marrow cells, we showed that EPO is also able to induce proliferation in pluripotent progenitor cells. After 7 days of coculture with virus-producing cells, bone marrow cells were plated in methylcellulose culture in the presence of EPO, interleukin-3, or Steel factor alone or in combination. In the presence of EPO alone, EPO-R virus-infected bone marrow cells gave rise to mixed colonies comprising erythrocytes, granulocytes, macrophages and megakaryocytes. The addition of interleukin-3 or Steel factor to methylcellulose cultures containing EPO did not significantly modify the number of mixed colonies. The cells which generate these mixed colonies have a high proliferative potential as shown by the size and the ability of the mixed colonies to give rise to secondary colonies. Thus, it appears that EPO has the same effect on EPO-R-expressing multipotent cell proliferation as would a combination of several growth factors. Finally, our results demonstrate that inducing pluripotent progenitor cells to proliferate via the EPO signaling pathway has no major influence on their commitment. PMID- 8007983 TI - Tyrosine 569 in the c-Fms juxtamembrane domain is essential for kinase activity and macrophage colony-stimulating factor-dependent internalization. AB - The receptor (Fms) for macrophage colony-stimulating factor (M-CSF) is a member of the tyrosine kinase class of growth factor receptors. It maintains survival, stimulates growth, and drives differentiation of the macrophage lineage of hematopoietic cells. Fms accumulates on the cell surface and becomes activated for signal transduction after M-CSF binding and is then internalized via endocytosis for eventual degradation in lysosomes. We have investigated the mechanism of endocytosis as part of the overall signaling process of this receptor and have identified an amino acid segment near the cytoplasmic juxtamembrane region surrounding tyrosine 569 that is important for internalization. Mutation of tyrosine 569 to alanine (Y569A) eliminates ligand induced rapid endocytosis of receptor molecules. The mutant Fms Y569A also lacks tyrosine kinase activity; however, tyrosine kinase activity is not essential for endocytosis because the kinase inactive receptor Fms K614A does undergo ligand induced endocytosis, albeit at a reduced rate. Mutation of tyrosine 569 to phenylalanine had no effect on the M-CSF-induced endocytosis of Fms, and a four amino-acid sequence containing Y-569 could support endocytosis when transferred into the cytoplasmic juxtamembrane region of a glycophorin A construct. These results indicate that tyrosine 569 within the juxtamembrane region of Fms is part of a signal recognition sequence for endocytosis that does not require tyrosine phosphorylation at this site and that this domain also influences the kinase activity of the receptor. These results are consistent with a ligand-dependent step in recognition of the potential cryptic internalization signal. PMID- 8007984 TI - Multiple forms of C/EBP beta bind the EFII enhancer sequence in the Rous sarcoma virus long terminal repeat. AB - In this report we demonstrate that C/EBP beta is a major component of three EFII DNA binding complexes, EFIIa, EFIIb, and EFIIc, which we have previously shown to specifically recognize a C/EBP consensus binding site found in the EFII enhancer sequence from the Rous sarcoma virus long terminal repeat (R. C. Sears and L. Sealy, J. Virol. 66:6338-6352, 1992). Three different forms of C/EBP beta, p42, p35, and p20, can bind the EFII DNA sequence as homodimers, and dimerization experiments show that EFIIa is a homodimer of p20 C/EBP beta, EFIIb is primarily composed of a p20/p35 heterodimer with minor amounts of p20/p42 heterodimer and p35 homodimer, and EFIIc is composed of p20 and/or p35 heterodimerized with a novel 60-kDa protein. p20 C/EBP beta is likely equivalent to the internally initiated translation product of C/EBP beta, LIP (liver inhibitor protein), described by P. Descombes and U. Schibler (Cell 67:569-579, 1991). In contrast to the low level of LIP expressed in liver, postulated to occur because of leaky ribosome scanning, we found high levels of expression of p20 C/EBP beta in fibroblasts and lymphocytes. In murine fibroblasts, p20 C/EBP beta has an extended half-life, four times longer than those of p42 and p35 C/EBP beta, which could contribute to its abundant accumulation in this cell type, even though its synthesis by leaky ribosome scanning might be inefficient. Interestingly, overexpression of either the long or short form of C/EBP beta represses EFII mediated transcription, suggesting that another unidentified EFII transactivator(s) exists, which may be dominantly inhibited by C/EBP beta proteins, and/or that transactivation by C/EBP beta proteins requires posttranslational modifications that were lacking in the transient overexpression experiments. PMID- 8007985 TI - Structural and functional conservation of the human homolog of the Schizosaccharomyces pombe rad2 gene, which is required for chromosome segregation and recovery from DNA damage. AB - The rad2 mutant of Schizosaccharomyces pombe is sensitive to UV irradiation and deficient in the repair of UV damage. In addition, it has a very high degree of chromosome loss and/or nondisjunction. We have cloned the rad2 gene and have shown it to be a member of the Saccharomyces cerevisiae RAD2/S. pombe rad13/human XPG family. Using degenerate PCR, we have cloned the human homolog of the rad2 gene. Human cDNA has 55% amino acid sequence identity to the rad2 gene and is able to complement the UV sensitivity of the rad2 null mutant. We have thus isolated a novel human gene which is likely to be involved both in controlling the fidelity of chromosome segregation and in the repair of UV-induced DNA damage. Its involvement in two fundamental processes for maintaining chromosomal integrity suggests that it is likely to be an important component of cancer avoidance mechanisms. PMID- 8007986 TI - Phosphatidylinositol 3-kinase activation is required for insulin stimulation of pp70 S6 kinase, DNA synthesis, and glucose transporter translocation. AB - Phosphatidylinositol 3-kinase (PI 3-kinase) is stimulated by insulin and a variety of growth factors, but its exact role in signal transduction remains unclear. We have used a novel, highly specific inhibitor of PT 3-kinase to dissect the role of this enzyme in insulin action. Treatment of intact 3T3-L1 adipocytes with LY294002 produced a dose-dependent inhibition of insulin stimulated PI 3-kinase (50% inhibitory concentration, 6 microM) with > 95% reduction in the levels of phosphatidylinositol-3,4,5-trisphosphate without changes in the levels of phosphatidylinositol-4-monophosphate or its derivatives. In parallel, there was a complete inhibition of insulin-stimulated phosphorylation and activation of pp70 S6 kinase. Inhibition of PI 3-kinase also effectively blocked insulin- and serum-stimulated DNA synthesis and insulin stimulated glucose uptake by inhibiting translocation of GLUT 4 glucose transporters to the plasma membrane. By contrast, LY294002 had no effect on insulin stimulation of mitogen-activated protein kinase or pp90 S6 kinase. Thus, activation of PI 3-kinase plays a critical role in mammalian cells and is required for activation of pp70 S6 kinase and DNA synthesis and certain forms of intracellular vesicular trafficking but not mitogen-activated protein kinase or pp90 S6 kinase activation. These data suggest that PI 3-kinase is not only an important component but also a point of divergence in the insulin signaling network. PMID- 8007987 TI - Complementation of a capsule-deficient mutation of Cryptococcus neoformans restores its virulence. AB - Capsule formation plays a significant role in the pathogenicity of Cryptococcus neoformans. To study the molecular basis of capsule synthesis, the capsule deficient phenotype of a mutant strain was complemented by transformation. A plasmid rescued from the resulting Cap+ transformant complemented a cap59 mutation which was mapped previously by classical recombination analysis. Gene deletion by homologous integration resulted in an acapsular phenotype, indicating that we have identified the CAP59 gene. The CAP59 gene was assigned to chromosome I by Southern blot analysis of contour-clamped homogeneous electric field gel electrophoresis-resolved chromosomes of C. neoformans var. neoformans. Sequence comparison of genomic and cDNA clones indicated the presence of six introns. CAP59 encoded a 1.9-kb transcript and a deduced protein of 458 amino acids. Analysis of the nucleotide sequence revealed little similarity to existing sequences in the data bank. When the capsule-deficient phenotype was complemented, the originally avirulent C. neoformans strain became virulent for mice. In addition, the acapsular strain created by gene deletion of CAP59 lost its virulence. This work demonstrates the molecular basis for capsule-related virulence and that the CAP59 gene is required for capsule formation. PMID- 8007988 TI - Multiple instability-regulating sites in the 3' untranslated region of the urokinase-type plasminogen activator mRNA. AB - In LLC-PK1 cells urokinase-type plasminogen activator (uPA) mRNA has a short half life. It is stabilized by inhibition of protein synthesis and by downregulation of protein kinase C (PKC). In the present study on uPA mRNA metabolism, we focused our attention on the 3' untranslated region (3'UTR) of the uPA mRNA, as this region is long and highly conserved among several mammalian species, including mice and humans. To investigate the possible role of the 3'UTR of uPA mRNA in mRNA metabolism, we inserted this region into the 3'UTR of the rabbit beta-globin gene that is linked to the cytomegalovirus promoter and stably transfected it into LLC-PK1 cells. While the parental globin mRNA was stable, the chimeric mRNA was degraded as rapidly as endogenous uPA mRNA, suggesting that the 3'UTR of uPA mRNA contains most of the information required for its rapid turnover. Further analysis showed that there are at least three independent determinants of instability in the 3'UTR; one is an AU-rich sequence located immediately 3' of the poly(A) addition signal, and one is a sequence containing a stem structure. One determinant seems to require ongoing RNA synthesis for its activity. All chimeric unstable globin mRNAs became stable in the presence of cycloheximide, a protein synthesis inhibitor, suggesting that the stabilization of mRNA by protein synthesis inhibition is not through a specific sequence in the mRNA. In PKC-downregulated cells, globin mRNAs with the complete 3'UTR or the AU rich sequence were stabilized, suggesting that PKC downregulation stabilizes uPA mRNA through the AU-rich sequence. Here we discuss the significance of multiple, independently acting instability determinants in the regulation of uPA mRNA metabolism. PMID- 8007989 TI - The yeast and mammalian Ras pathways control transcription of heat shock genes independently of heat shock transcription factor. AB - Yeast strains in which the Ras-cyclic AMP (cAMP) pathway is constitutively active are sensitive to heat shock, whereas mutants in which the activity of this pathway is low are hyperresistant to heat shock. To determine the molecular basis for these differences, we examined the transcriptional induction of heat shock genes in various yeast strains. Activation of heat shock genes was attenuated in the strains in which the Ras-cAMP pathway is constitutively active. In contrast, in a strain deficient in cAMP production, several heat shock genes were induced by removal of cAMP from the medium. These results indicate that the Ras-cAMP pathway affects the induction of heat shock genes. In all of the mutants, heat shock transcription factor expression and activity were identical to those in wild-type cells. The response to heat shock in Ha-ras-transformed rat fibroblasts was also studied. While no induction of Hsp68 was observed in Ha-ras-transformed cells, proper regulation of heat shock transcription factor was found. Therefore, in mammals, as in Saccharomyces cerevisiae, the Ras pathway controls the transcription of heat shock genes via a mechanism not involving the heat shock transcription factor. PMID- 8007990 TI - Transcription factor GATA-4 regulates cardiac muscle-specific expression of the alpha-myosin heavy-chain gene. AB - The alpha-myosin heavy-chain (alpha-MHC) gene is the major structural protein in the adult rodent myocardium. Its expression is restricted to the heart by a complex interplay of trans-acting factors and their cis-acting sites. However, to date, the factors that have been shown to regulate expression of this gene have also been found in skeletal muscle cells. Recently, transcription factor GATA-4, which has a tissue distribution limited to the heart and endodermally derived tissues, was identified. We recently found two putative GATA-binding sites within the proximal enhancer of the alpha-MHC gene, suggesting that GATA-4 might regulate its expression. In this study, we establish that GATA-4 interacts with the alpha-MHC GATA sites to stimulate cardiac muscle-specific expression. Mutation of the GATA-4-binding sites either individually or together decreased activity by 50 and 88% in the adult myocardium, respectively. GATA-4-dependent enhancement of activity from a heterologous promoter was mediated through the alpha-MHC GATA sites. Coinjection of an alpha-MHC promoter construct with a GATA 4 expression vector permitted ectopic expression in skeletal muscle but not in fibroblasts. Thus, the lack of alpha-MHC expression in skeletal muscle correlates with a lack of GATA-4. GATA-4 DNA binding activity was significantly up-regulated in triiodothyronine- or retinoic acid-treated cardiomyocytes. Putative GATA-4 binding sites are also found in the regulatory regions of other cardiac muscle expressed structural genes. This indicates a mechanism whereby triiodothyronine and retinoic acid can exert coordinate control of the cardiac phenotype through a trans-acting regulatory factor. PMID- 8007992 TI - Loss of serum response element-binding activity and hyperphosphorylation of serum response factor during cellular aging. AB - Human diploid fibroblasts undergo a limited number of population doublings in vitro and are used widely as a model of cellular aging. Despite growing evidence that cellular aging occurs as a consequence of altered gene expression, little is known about the activity of transcription factors in aging cells. Here, we report a dramatic reduction in the ability of proteins extracted from the nuclei of near senescent fibroblasts to bind the serum response element which is necessary for serum-induced transcription of the c-fos gene. In contrast, the activities of proteins binding to the RNA polymerase core element, TATA, as well as to the cyclic AMP response element were maintained during cellular aging. While no major differences in the expression of the serum response factor (SRF) that binds the serum response element were seen between early-passage and late-passage cells, hyperphosphorylation of SRF was observed in near-senescent cells. Furthermore, removal of phosphatase inhibitors during the isolation of endogenous nuclear proteins restored the ability of SRF isolated from old cells to bind the SRE. These data, therefore, indicate that hyperphosphorylation of SRF plays a role in altering the ability of this protein to bind to DNA and regulate gene expression in senescent cells. PMID- 8007995 TI - Central fatigue as revealed by postexercise decrement of motor evoked potentials. AB - We have previously shown that the amplitudes of motor evoked potentials (MEPs) elicited by transcranial magnetic stimulation (TMS) were transiently decreased after exercise, indicating fatigue of motor pathways in the central nervous system. The responsible mechanism is apparently decreased efficiency in the generation of the descending volleys in the motor cortex. We also noted a progressive decrement in amplitude from the first to the fourth MEP. To further clarify the mechanism of this phenomenon, 5 subjects were studied with TMS delivered at the rates of 0.1, 0.15, 0.3, 1, 3, and 6 Hz. The effect was best demonstrated at 0.3 Hz, and occurred after both isometric and isotonic exercise. Three of the subjects also had 0.3-Hz percutaneous electrical stimulation of the brainstem, and a decrement in MEP amplitude did not occur. Further, the delivery of TMS during muscle contraction after muscle fatigue failed to produce a decrement. The results are similar to those found at the neuromuscular junction in myasthenia gravis and are consistent with a reduced safety factor of cortical synaptic transmission in central nervous system fatigue. PMID- 8007991 TI - Novel interactions between human T-cell leukemia virus type I Tax and activating transcription factor 3 at a cyclic AMP-responsive element. AB - Human proenkephalin gene transcription is transactivated by human T-cell leukemia virus type I (HTLV-I) Tax in human Jurkat T lymphocytes. This transactivation was further enhanced in Jurkat cells treated with concanavalin A, cyclic AMP, or 12-O tetradecanoylphorbol-13-acetate. Deletion and cis-element transfer analyses of the human proenkephalin promoter identified a cyclic AMP-responsive AP-1 element (-92 to -86) as both necessary and sufficient to confer Tax-dependent transactivation. Different AP-1 or cyclic AMP-responsive element-binding protein (CREB)/activating transcription factor (ATF) proteins which bind this element were expressed in murine teratocarcinoma F9 cells to identify those capable of mediating Tax-dependent transactivation of human proenkephalin gene transcription. Although CREB, c-Fos, c-Jun, and JunD did not have significant effects, JunB inhibited the Tax-dependent transactivation. In contrast, ATF3 dramatically induced Tax-dependent transactivation, which was further enhanced by protein kinase A. Electrophoretic mobility shift assays with recombinant fusion proteins expressed and purified from bacteria indicate that the DNA-binding activity of ATF3 is also dramatically enhanced by Tax. Chimeric fusion proteins consisting of the DNA-binding domain of the yeast transcription factor Gal4 and the amino-terminal domain (residues 1 to 66) of ATF3 were able to mediate Tax dependent transactivation of a Gal4-responsive promoter, which suggests a direct involvement of this region of ATF3. Recombinant fusion proteins of glutathione S transferase with either the amino- or carboxy-terminal (residues 139 to 181) domain of ATF3 were able to specifically interact with Tax. Furthermore, specific antisera directed against Tax coimmunoprecipitated ATF3 only in the presence of Tax. PMID- 8007997 TI - Does forearm mixed nerve conduction velocity reflect retrograde changes in carpal tunnel syndrome? AB - The mixed nerve conduction velocity of the median nerve in the forearm diverged from the motor and sensory nerve conduction velocities and correlated poorly with the severity of carpal tunnel syndrome (CTS) in 61 hands. In contrast, the motor and sensory nerve conduction velocities in the forearm correlated well with CTS severity. The mixed nerve conduction velocity in the forearm is probably determined by nonlesioned fibers such as those from the cutaneous palmar branch of the median nerve. The motor and sensory, but not the mixed nerve conduction velocities in the forearm may be used to estimate possible retrograde impairment in CTS. PMID- 8007994 TI - Factor C*, the specific initiation component of the mouse RNA polymerase I holoenzyme, is inactivated early in the transcription process. AB - Factor C* is the component of the RNA polymerase I holoenzyme (factor C) that allows specific transcriptional initiation on a factor D (SL1)- and UBF-activated rRNA gene promoter. The in vitro transcriptional capacity of a preincubated rDNA promoter complex becomes exhausted very rapidly upon initiation of transcription. This is due to the rapid depletion of C* activity. In contrast, C* activity is not unstable in the absence of transcription, even in the presence of nucleoside triphosphates (NTPs). By using 3'dNTPs to specifically halt elongation, C* is seen to remain active through transcription complex assembly, initiation, and the first approximately 37 nucleotides of elongation, but it is inactivated before synthesis proceeds beyond approximately 40 nucleotides. When elongation is halted before this critical distance, the C* remains active and on that template complex, greatly extending the kinetics of transcription and generating manyfold more transcripts than would have been synthesized if elongation had proceeded past the critical distance where C* is inactivated. In complementary in vivo analysis under conditions where C* activity is not replenished, C* activity becomes depleted from cells, but this also occurs only when there is ongoing rDNA transcription. Thus, both in vitro and in vivo, the specific initiation conferring component of the RNA polymerase I holoenzyme is used stoichiometrically in the transcription process. PMID- 8007993 TI - E2F and its developmental regulation in Xenopus laevis. AB - The transcription factor E2F has been implicated in cell cycle control by virtue of its association with cyclins, cyclin-dependent kinases, and pRb-related tumor suppressor gene products. Eggs and embryos from the frog Xenopus laevis have been used to investigate the characteristics of E2F-like molecules in the Xenopus cell cycle and throughout early development. We find multiple E2F species in Xenopus eggs, at least one of which is modified by phosphorylation. The vast majority of E2F remains in the free form throughout the very early embryonic cell cycle, and it also remains predominantly free until some time after the mid-blastula transition, the onset of zygotic transcription. At this time, E2F complexes significantly to pRb but not to cdk2, although cdk2 binding is found in tissue culture cells from a very advanced stage in embryogenesis. This suggests that the complexing of E2F to cyclins, cyclin-dependent kinases, and tumor suppressor gene products may be controlled separately in early Xenopus development. Thus, the association of E2F with other molecules may not result solely from processes affecting cell cycle progression but may also reflect developmental and differentiation cues. PMID- 8007996 TI - Expression of myoglobin gene in skeletal muscle of patients with neuromuscular diseases. AB - Expression of the myoglobin (Mb) gene in skeletal muscle was studied in patients with Duchenne muscular dystrophy (DMD), polymyositis (PM), or amyotrophic lateral sclerosis (ALS) by measuring Mb concentration by radioimmunoassay and Mb messenger ribonucleic acid (RNA) (MbmRNA) levels by Northern blot analysis. Mb concentrations in the muscle cells (Mb/noncollagenous protein) were decreased in patients with DMD, PM, or ALS. However, while Mb concentrations per MbmRNA content (Mb/MbmRNA) were decreased in DMD and PM patients, these values were normal in ALS patients. These results suggest that Mb synthesis is increased in muscles of DMD and PM patients, but is not sufficient to compensate for the excessive loss of Mb from the affected muscles, and that the synthesis is decreased in the muscles of ALS patients. PMID- 8007998 TI - Tuberculous infection of skeletal muscle in a case of dermatomyositis. AB - A patient with dermatomyositis associated with carcinoma was treated with steroids and antibiotics for possible tuberculosis. Autopsy showed an overwhelming diffuse nongranulomatous infection of Mycobacterium tuberculosis involving only the skeletal muscles and one inguinal lymph node. The rare localization of tuberculosis to skeletal muscle in this case is possibly due to steroid immunosuppression and the humoral immune attack on muscle blood vessels that is a part of dermatomyositis. PMID- 8007999 TI - Compound sensory action potentials evoked by tactile and by electrical stimulation in normal median and sural nerves. AB - The compound sensory action potential evoked by electrical stimulation provides a measure of the number and physiological properties of myelinated fibers in the nerve but does not allow evaluation of the most distal part of the sensory nerve. This study compares the compound sensory action potential, evoked by electrical and tactile stimuli, and recorded through needle electrodes placed close to the median and sural nerves of 22 normal males aged 16-51 years. The tactile probe, with a slight preindentation, delivered an indentation of the skin of 200 microns at a rate of 400 microns/ms at the tip of digit III and the dorsolateral side of the foot. The responses were recorded from the median nerve at wrist and elbow and from the sural nerve at the lateral malleolus and midcalf. The amplitudes of the responses averaged 0.5 microV and 0.7 microV in the sural and the median nerves (P < 0.02), respectively, which was only 5-10% of the amplitude evoked by electrical stimulation. The mean maximal conduction velocity determined by tactile stimulation was 54 m/s in the sural nerve compared with 65 m/s in the median nerve and similar to that calculated after electrical stimulation. In the median nerve the sensory conduction velocity was 8% faster than the motor conduction velocity. These findings indicated that only a fraction of the fibers in the nerve were activated by the probe and that the response was conducted along large myelinated sensory fibers. The latency of the tactile response was longer than that of the electrically evoked response due to the receptor delay and conduction along thin distal fiber portions. The delay at the mechanoreceptors was about 1 ms in the sural and 0.65 ms in the median nerve (P < 0.01). PMID- 8008000 TI - Widespread tissue distribution of multiple mitochondrial DNA deletions in familial mitochondrial myopathy. AB - We used Southern blot analysis and the polymerase chain reaction to analyze the tissue distribution of multiple mitochondrial DNA (mtDNA) deletions in a 45-year old man with familial mitochondrial myopathy-Southern blots showed two major types of abnormal mtDNA with approximately 4- and 8-kilobase deletions in the skeletal and extraocular muscles. The amount of muscle mtDNA with deletions correlated approximately with the severity of muscle involvement. The polymerase chain reaction showed multiple mtDNA deletions even in clinically asymptomatic tissues, the pattern of which differed with the type of tissue. Nucleotide sequences of several mtDNAs with deletions showed that the deletions were flanked by direct repeats consisting of 3 to 12 nucleotides. Leukocytes from the patient's affected sister and his mother exhibited the same mtDNA deletion pattern. Most of the same deletions were present in leukocytes obtained from the patient's father. PMID- 8008001 TI - Decremental motor responses to repetitive nerve stimulation in ALS. AB - Repetitive nerve stimulation (RNS) of the trapezius muscle at slow rates was performed on 192 patients with amyotrophic lateral sclerosis (ALS). Fifty-six patients (29%) showed classical neuromuscular decrement of 10-43% (mean 16.8%) while 44 patients (23%) had a borderline decrement of 5-9%. The trapezius was significantly more sensitive in revealing the defect than the distal hypothenar muscles. In 30 patients followed serially, the decremental response remained constant or increased with time. However, 25% of patients continued to show no decrement in spite of progression of disease. No statistical correlation was found between decrement and clinical severity, disease staging, or disease progression. The finding that at least 50% of ALS patients show some degree of decrement on RNS of the trapezius muscle suggests that functional alterations of the neuromuscular junction accompany this disease. PMID- 8008002 TI - Pediatric median mononeuropathies: a clinical and electromyographic study. AB - Seventeen children, 6 girls and 11 boys, aged 5-17 years with pediatric median mononeuropathies (PMM) were identified among 1809 who had EMGs primarily in the electromyographic laboratory at The Children's Hospital, Boston, between 1979 and 1993. Electromyography documented the PMM to be at the wrist in 7 children, including 3 children with idiopathic carpal tunnel syndrome (CTS)--1 whose symptoms were accentuated by skiing--2 with a systemic illness (mucolipidosis III and scleroderma), and in 1 child each the distal PMM was secondary to a cast or laceration. A proximal PMM was identified in 10 children, including 8 with trauma, 1 with an osteoid osteoma, and 1 with juvenile cutaneous mucinosis. Five children (3 with CTS and 1 each with mucolipidosis III and juvenile cutaneous mucinosis) had bilateral disease. The localization (59% proximal) and cause of these PMMs differed greatly from our experience with adult median neuropathies. PMID- 8008003 TI - Paramyotonia congenita: abnormal short exercise test, and improvement after mexiletine therapy. AB - The diagnosis of paramyotonia congenita (PC) can be aided by demonstrating a decrease in compound motor action potential amplitude after exercise and a decrement on repetitive stimulation, following cold exposure. We report a patient with PC who presented with complaints of cold-induced hand and jaw stiffening, in the absence of any episodes of weakness. Treatment with mexiletine led to resolution of the abnormalities exhibited during a short exercise test and repetitive stimulation following ice bath immersion. Molecular genetic analysis revealed a missense mutation (cytosine to thymidine) on chromosome 17 in the alpha-subunit of the skeletal muscle sodium channel gene that results in the replacement of threonine with methionine. This case demonstrates that, despite the absence of weakness, the short exercise test following cold exposure can be used to confirm the diagnosis of PC in patients without episodic weakness. Furthermore, improvement of the electrophysiologic abnormalities with mexiletine was documented, corresponding with clinical improvement. PMID- 8008004 TI - Acute postasthmatic amyotrophy (Hopkins' syndrome). AB - Acute postasthmatic amyotrophy is a rare condition, previously reported in only 26 cases. It is characterized by a sudden onset of a flaccid paralysis of an arm or a leg with completely preserved sensibility, about 1 week after an asthmatic attack. The cause is probably due to a lesion of the anterior horn of the spinal cord, but evidence indicates a more widespread pathological process. The etiology is unknown, but infectious or immunological mechanisms are likely. PMID- 8008006 TI - Botulinum toxin converts muscle acetylcholine receptors from adult to embryonic type. AB - To assess the postsynaptic consequences of botulinum toxin injection into muscle we characterized the nicotinic acetylcholine receptor (nAChR) with the patch clamp technique, using adult mouse muscle after destruction of the nerve ending and after treatment with botulinum toxin (BoTX). In both, embryonic channels with a conductance of 30 and 34 pS could be identified, whereas on adult control muscle nAChR channels had a conductance of 48 pS. The mean open times were 1.2 ms for the channels in control, 2.5 ms in denervated and 2.4 ms in BoTX-treated muscle. The dose-response curves of the maximal acetylcholine-elicited currents showed a Km of 60 mumol/L for denervated, 70 mumol/L for BoTX-treated, and 100 mumol/L for control muscle. Destruction of the nerve ending and inhibition of acetylcholine release by BoTX has the same effect as far as the increase of sensitivity of the muscle to acetylcholine is concerned. In contrast to single fiber EMG findings in patients treated for focal dystonia no distant changes could be found in the control muscle of the BoTX-treated animals. PMID- 8008005 TI - Conduction velocity in motor, cutaneous afferent, and muscle afferent fibers within the same mixed nerve. AB - Mammalian axons subserving different functions have different conduction velocities (CV); motor fibers conduct more slowly than cutaneous fibers, which conduct slower than muscle afferents. However, human studies have yielded conflicting results. We studied isolated fiber populations in human sciatic nerve to examine further this question. Motor studies were performed in standard fashion, stimulating at gluteal fold (GF) and popliteal fossa (PF) and recording soleus. In addition, conduction velocity of a pure motor nerve volley was calculated for 3 subjects. Stimulating and recording electrodes were needles placed close to the nerve. Cutaneous afferents were studied by stimulating the sural nerve at the ankle and recording at PF and GF. Muscle afferent velocity was assessed by comparing soleus H reflex latency with stimulation at PF and GF. Results in 10 subjects showed muscle afferent CV of 57.6, cutaneous afferent CV of 55.1, motor CV of 52.4, and mixed nerve CV of 56.3 m/s. Although statistically significant, these differences are much smaller than in animal studies. These results have implications for understanding what fibers contribute to spinal reflexes. PMID- 8008007 TI - Sensory and mixed nerve conduction studies in the evaluation of ulnar neuropathy at the elbow. AB - The relative sensitivities of sensory, mixed nerve, and motor conduction studies in assessing ulnar neuropathy at the elbow have not yet been established. Using surface electrodes, we performed conduction studies across the elbow segment in 43 patients with symptoms referable to the ulnar nerve and 40 control subjects. Segmental slowing of motor conduction localized the lesion to the elbow in 14 of 21 patients (67%) with clear evidence of ulnar neuropathy on physical examination but only in 2 of 22 (9%) with subtle or no physical examination abnormalities. The diagnostic yield was increased by the finding of segmental slowing of sensory or mixed nerve conduction across the elbow to 86% and 68%, respectively, for each of the groups. We conclude that surface-recorded sensory and mixed nerve conduction studies appear to be more sensitive than motor studies in the electrodiagnosis of ulnar neuropathy at the elbow and are especially valuable in patients with subtle clinical involvement. PMID- 8008008 TI - Acute peripheral neuropathy due to hereditary coproporphyria. AB - A 23-year-old man with epilepsy and a past history of abdominal pain and ileus, developed hypertension and arm and bulbar weakness when valproic acid and carbamazepine were reinitiated. Electrophysiologic studies demonstrated a peripheral neuropathy with features of axonal degeneration and demyelination. Axonal degeneration was documented by sural nerve biopsy. Markedly elevated urinary delta-aminolevulinic acid and porphobilinogen indicated a diagnosis of acute porphyria. Other laboratory studies were most consistent with hereditary coproporphyria. Motor function improved considerably but incompletely over 1 year. An acute, primarily motor neuropathy can occur in several forms of porphyria, including acute intermittent porphyria, variegate porphyria, and hereditary coproporphyria, sometimes even in the absence of concomitant gastrointestinal symptoms. PMID- 8008010 TI - The dropped head syndrome with chronic inflammatory demyelinating polyneuropathy. AB - The dropped head syndrome occurs in a variety of neuromuscular disorders. We present a woman with chronic inflammatory demyelinating polyneuropathy who developed this syndrome, likely reflecting severe demyelination of nerves to cervical paraspinal muscles. PMID- 8008009 TI - Resetting of essential tremor and postural tremor in Parkinson's disease with transcranial magnetic stimulation. AB - We studied the effects of transcranial motor cortex stimulation on the electromyographic characteristics of tremor in 9 patients with familial essential tremor and in 12 patients with postural tremor associated with Parkinson's disease. Transcranial magnetic stimulation reset both types of tremor equally. The resetting depended on the stimulus intensity, but was most closely correlated with the duration of the electromyographic silent period that followed the stimulus-induced motor evoked potential. Tremor resetting was present bilaterally even after focal, unilateral stimulation. Transcranial electrical stimulation failed to reset the tremor in either patient group. These results emphasize the role of central, intracortical structures in the generation of essential tremor and postural tremor in Parkinson's disease. PMID- 8008011 TI - Statistical errors and their effect on electrodiagnostic medicine. AB - Failure to demonstrate abnormalities on diagnostic tests in patients felt certain to have a disease is all too common, especially when symptoms are mild to moderate. One strategy used in such cases is to perform multiple tests hoping that one will confirm the clinical suspicion. An example of this strategy is found in carpal tunnel syndrome where multiple tests are often used to confirm the diagnosis. Unfortunately, this approach is often erroneous. Since no diagnostic test can perfectly discriminate between normal and abnormal, critical values are set at levels where most subjects are correctly classified. Using this methodology, approximately 2.5% of patients who are normal will be mistakenly called abnormal. This type I error, is additive when additional independent tests are performed. Since no two tests for a single condition are completely independent, the total error is less than the sum of the individual errors for each test. Even after accounting for interdependency, the total error of combined tests may be unacceptably high. If a single, highly discriminating, test is not available and multiple tests are used, abnormalities in more than a single test are needed to distinguish between normals and abnormals. PMID- 8008012 TI - Diagnostic tests: a statistical review. AB - Common measures of the accuracy of diagnostic tests are reviewed. It is shown that the actual performance (predictive value) of these tests depends not only on their sensitivity and specificity, but also on the prevalence of the disease in the population tested (Bayes' theorem). The effect of an inaccurate "gold standard" on the calibration of a new diagnostic test is discussed. Receiver operating characteristic (ROC) curves are introduced as a tool for selecting an optimal cutpoint for a test, and for comparing different tests. Schemes are given for combining tests to improve their accuracy. When multiple continuous measurements are available, methods of discriminant analysis (and logistic regression) are shown to provide measurement combinations with improved accuracy. Examples and key references are provided. PMID- 8008013 TI - Single fiber EMG reference values: reformatted in tabular form. AD HOC Committee of the AAEM Single Fiber Special Interest Group. PMID- 8008015 TI - Long duration polyphasic motor unit potentials in myopathic disorders. PMID- 8008014 TI - Lack of Toxoplasma gondii DNA in muscles of patients with inflammatory myopathy and increased anti-Toxoplasma antibodies. PMID- 8008016 TI - Management of kineceptive loss in CMT with an elastic ankle support. PMID- 8008017 TI - Characterization of phosphatidylinositol synthase and evidence of a polyphosphoinositide cycle in Plasmodium-infected erythrocytes. AB - Plasmodium knowlesi-infected erythrocytes possess a membranous cytidine 5' diphospho-1,2-diacyl-sn-glycerol: myoinositol 3-phosphatidyl transferase (PI synthase) (EC 2.7.8.11) activity of 10 +/- 1.7 nmol min-1 per 10(10) infected cells. The activity was successfully solubilized with 40 mM n-octyl-beta-D glucopyranoside in the presence of bivalent metal ions which were absolutely required for activity. The optimal pH was 8 and the apparent Ks for Mn2+ was 0.1 mM. Mg2+ allowed two-fold higher PI synthase activity, with an optimum above 100 mM. Calcium alone was ineffective while at 2 mM it inhibited solubilized PI synthase activity in the presence of 100 mM Mg2+. Enzymatic activity was fully dependent on CDP-diacylglycerol and inositol with apparent Km of 0.16 +/- 0.1 mM and 1 +/- 0.5 mM respectively. Affinity chromatography clearly showed CDP diacylglycerol-dependent interactions of PI synthase with CDP-diacylglycerol Sepharose. However, elution of enzymatic activity in an active form was unsuccessful while SDS-PAGE of the eluate showed one apparent band. Incubations of Plasmodium falciparum-infected erythrocytes with 32P or [3H]inositol revealed de novo biosynthesis of phosphatidylinositol, phosphatidylinositol 4-phosphate and phosphatidylinositol 4,5-bisphosphate which appeared to predominate in the second half of the asexual cellular cycle. Ionomycin, a calcium ionophore, induced Li(+)-sensitive production of radioactive inositol phosphates, with neo synthesized inositol 1,4,5-trisphosphate accumulation being the highest. PMID- 8008018 TI - Plasmodium falciparum genetic diversity can be characterised using the polymorphic merozoite surface antigen 2 (MSA-2) gene as a single locus marker. AB - The genetic diversity of Solomon Island Plasmodium falciparum isolates was examined using MSA-2 as a single locus marker. Amplification of MSA-2 gene fragments showed size polymorphism and the presence of mixed infections. Sequence analysis indicated a global representation of MSA-2 alleles with representatives of 3D7/CAMP allelic subfamilies and the FCQ-27 allelic family being identified. A simplified method of characterisation, utilising PCR-RFLPs of MSA-2 gene fragments, was developed. The RFLPs allowed identification of allelic families and further distinction within the 3D7/CAMP family. The amplification of MSA-2 gene fragments from culture derived lines revealed a loss of diversity for a number of Solomon Island isolates. Genomic diversity was confirmed for Solomon Island lines, along with Papua New Guinean and Thai lines, by the generation of 7H8/6 fingerprints. All lines were distinct and band sharing frequencies and Wagner tree construction failed to identify any geographic clustering. PMID- 8008019 TI - Null mutants for the lmcpa cysteine proteinase gene in Leishmania mexicana. AB - The parasitic protozoon Leishmania mexicana possesses an abundance of developmentally regulated cathepsin L-like cysteine proteinases expressed at highest levels in amastigotes. We recently characterised lmcpa, a single-copy gene encoding one such proteinase, LmCPa, which differs from other homologues by possessing a 3-amino-acid insertion at the amino terminal of the predicted mature proteinase. To investigate the role of LmCPa in L. mexicana, we used gene targeting of promastigotes with hygromycin- and phleomycin-resistance markers to generate null mutants by disrupting sequentially both alleles of lmcpa. The promastigote null mutants did not differ significantly from wild-type L. mexicana in growth rate or morphology and could differentiate to metacyclics and the amastigote-like form, both of which could infect the J774G8 macrophage-like cell line. The null mutant amastigote-like form obtained from the J774G8 cells could also establish rump lesions in CBA mice. By these criteria, therefore, LmCPa appears to be non-essential although there is the possibility that LmCPa could be required during development in the sandfly, a stage not analysed here. The apparent redundancy of LmCPa in amastigotes may be due to the presence of other cysteine proteinases and has implications for the choice of candidate targets for rationally designed anti-leishmanial drugs. PMID- 8008020 TI - Isolation, sequencing and expression of the gene encoding hypoxanthine-guanine xanthine phosphoribosyltransferase of Tritrichomonas foetus. AB - We have cloned and expressed the full-length gene encoding the hypoxanthine guanine-xanthine phosphoribosyltransferase (HGXPRTase) from the anaerobic protozoan parasite Tritrichomonas foetus. This enzyme is essential in nucleic acid metabolism of T. foetus because the parasite is unable to synthesize purine nucleotides de novo and relies on the HGXPRTase activities for its purine requirements. Initially, a cDNA clone encoding part of the HGXPRTase was isolated by complementation of an Escherichia coli mutant, SO609, with a cDNA library of T. foetus. Northern blot analysis identified a single mRNA band of approximately 700-800 bases. The full-length genomic clone was then isolated and identified to have an open reading frame of 549 bp encoding an 183-amino acid sequence with an estimated size of 21.1 kDa. The sequence is only 27.3% identical to that of the human HGPRTase. The T. foetus HGXPRTase gene was subsequently cloned into the pBAce vector for expression in E. coli. This construct yields completely soluble and enzymatically active recombinant T. foetus HGXPRTase, which constitutes approximately 20% of the total cellular protein of the transformed E. coli. It has the same molecular weight as the authentic native enzyme, and the N-terminal amino acid sequence of the recombinant enzyme is identical to that predicted from the open reading frame. The high expression of this apparently native T. foetus HGXPRTase will provide large quantities of purified protein, necessary for detailed kinetic and structural analysis of this enzyme for its potential value as a target for antitrichomonial chemotherapy. To our knowledge, this is also the first time a gene from T. foetus was cloned and expressed. PMID- 8008021 TI - Leishmania major HEXBP deletion mutants generated by double targeted gene replacement. AB - The Leishmania major single-stranded DNA binding protein HEXBP contains nine 'CCHC' zinc finger motifs and binds to oligodeoxynucleotides derived from the antisense strand of the GP63 gene 5' flanking region in gel mobility shift assays and UV-crosslinking assays. In the present study a HEXBP-deficient clone of L. major was generated by double targeted gene replacement. The two HEXBP alleles were sequentially replaced with genes encoding resistance to the aminoglycoside antibiotics hygromycin B and G418 and drug-resistant clones were selected by plating on semi-solid drug-containing media. Successful deletion of both copies of the HEXBP gene implies that HEXBP is a not essential for growth of Leishmania promastigotes. Characterization HEXBP-deficient promastigotes revealed that HEXBP deficiency had no effect on the abundance of GP63 mRNA and protein in in vitro cultivated promastigotes and that HEXBP-deficient promastigotes were capable of lesion formation in BALB/c mice. PMID- 8008022 TI - Homologous recombination and gene replacement at the dihydrofolate reductase thymidylate synthase locus in Toxoplasma gondii. AB - To investigate the feasibility of genomic transgene expression and gene targeting in Toxoplasma gondii, parasites have been transfected with constructs differing in the length of contiguous genomic sequence spanning the dihydrofolate reductase thymidylate synthase (DHFR-TS) gene. We have previously reported that vectors derived from a DHFR-TS cDNA 'minigene' containing mutations in the DHFR coding sequence confer pyrimethamine resistance to transfected parasites (Donald and Roos, 1993). Stably resistant parasite clones arise at high frequency, generally by virtue of transgene integration into parasite chromosomes at locations scattered throughout the genome. In contrast, using a vector which contains 8 kb of contiguous genomic sequence (vs. < 2 kb for the cDNA-derived vectors), approximately half of the integration events occur by homologous recombination. Homologous recombination appears to occur at even higher frequency when a 16 kb genomic clone is used. Circular plasmids were more efficient than linearized molecules at producing homologous recombination in this system, integrating by reciprocal crossing-over to produce a duplication of the DHFR-TS locus. Double crossing-over (or gene conversion) was also observed at low frequency, resulting in complete allelic replacement in this haploid stage of the parasite. The ability to produce either homologous or non-homologous recombinants, by the selection of appropriate transformation constructs, has considerable genetic potential. PMID- 8008023 TI - Purification and characterization of dihydrofolate reductase of Plasmodium falciparum expressed by a synthetic gene in Escherichia coli. AB - We have expressed the dihydrofolate reductase (DHFR) part of the DHFR-thymidylate synthetase complex of P. falciparum in Escherichia coli, by constructing a gene with synthetic oligonucleotides that changed the gene's codon usages. The induced expression in an E. coli cell of the synthetic gene yielded a product that constituted about 30% of the total bacterial protein. The product was precipitated in an inclusion body in a cell. Its enzymatic activity was restored after denaturation and renaturation procedures with guanidine-HCl. Recombinant DHFRs with Ser or Thr at position 108 were prepared. Kinetic characterization showed that the DHFRSer108 has less of an affinity for NADPH and dihydrofolate than the DHFRThr108. PMID- 8008024 TI - Virus-like particles in Eimeria nieschulzi are associated with multiple RNA segments. AB - RNA preparations from sporulated oocysts of Eimeria nieschulzi were found to contain 2 double-stranded RNA segments of 5.0 kb and 5.7 kb that were not present in other species of Eimeria. Treatment of crude lysates with RNase A revealed that in addition to these two segments, 3 other segments of 0.57 kb, 0.72 kb and 11.5 kb were protected from digestion, suggesting that they were enclosed within particles. Virus-like particles with a diameter of approximately 39 nm were purified by caesium chloride buoyant density centrifugation. Four of the five RNA segments copurified with these particles. In keeping with the nomenclature generally adopted for protozoan viruses, we have named this new isolate ENV 1. The largest RNA segment does not cosediment with ENV 1 particles and may be derived from another RNA-protein complex that is unstable under the conditions used. The particle size and genome structure of ENV 1 both differ from that of the Eimeria stiedae virus (ESV), which is the only other virus to have been isolated from Eimeria to date. Short cDNA clones derived from ENV 1 show significant homology to a region of the Leishmania virus (LRV 1) genome that encodes an RNA-dependent RNA polymerase. The polymerase sequences from ENV 1 and LRV 1 are more closely related to each other than to any other protein sequences in the GenEMBL Database. This raises intriguing questions about the origins of the two viruses, since Eimeria and Leishmania normally infect different hosts and also show different cell tropisms within these hosts. PMID- 8008025 TI - Regular initiation of translation of Plasmodium berghei aldolase-2 after pre-mRNA splicing. AB - In Plasmodium falciparum aldolase a UAG or a regular AUG codon has been proposed for the initiation of ribosomal protein synthesis. A UAG codon present at the beginning of the coding sequence of the aldolase 2 gene (aldo-2) of Plasmodium berghei is not recognised in vitro as an initiation codon, which suggests addition of a regular AUG codon by mRNA splicing. Sequence analysis of cDNA amplified by the reversed polymerase chain reaction reveals addition of an ATG codon with a splice donor consensus sequence to the aldo-2 exon. By the same technique and northern blot analysis, substantial amounts of partially spliced P. berghei aldo-2 precursor mRNA are detected which could explain the isolation of immature P. falciparum aldolase cDNA clones starting with a stop codon. PMID- 8008026 TI - Isolation, sequence and expression of an Onchocerca volvulus glutathione S transferase cDNA. PMID- 8008027 TI - A clinical trial of antioxidant vitamins to prevent colorectal adenoma. Polyp Prevention Study Group. AB - BACKGROUND: People who consume a diet high in vegetables and fruits have a lower risk of cancer of the large bowel. Antioxidant vitamins, which are present in vegetables and fruits, have been associated with a diminished risk of cancers at various anatomical sites. We conducted a randomized, controlled clinical trial to test the efficacy of beta carotene and vitamins C and E in preventing colorectal adenoma, a precursor of invasive cancer. METHODS: We randomly assigned 864 patients, using a two-by-two factorial design, to four treatment groups, which received placebo; beta carotene (25 mg daily); vitamin C (1 g daily) and vitamin E (400 mg daily); or the beta carotene plus vitamins C and E. In order to identify new adenomas, we performed complete colonoscopic examinations in the patients one year and four years after they entered the study. The primary end points for analyses were new adenomas identified after the first of these two follow-up examinations. RESULTS: Patients adhered well to the prescribed regimen, and 751 completed the four-year clinical trial. There was no evidence that either beta carotene or vitamins C and E reduced the incidence of adenomas; the relative risk for beta carotene was 1.01 (95 percent confidence interval, 0.85 to 1.20); for vitamins C and E, it was 1.08 (95 percent confidence interval, 0.91 to 1.29). Neither treatment appeared to be effective in any subgroup of patients or in the prevention of any subtype of polyp defined by size or location. CONCLUSIONS: The lack of efficacy of these vitamins argues against the use of supplemental beta carotene and vitamins C and E to prevent colorectal cancer. Although our data do not prove definitively that these antioxidants have no anticancer effect, other dietary factors may make more important contributions to the reduction in the risk of cancer associated with a diet high in vegetables and fruits. PMID- 8008028 TI - A molecular approach to the stratification of cardiovascular risk in families with Marfan's syndrome. AB - BACKGROUND: The fibrillin gene encodes a protein in the extracellular matrix, and this protein is widely distributed in elastic tissues. The fibrillin gene is the site of mutations causing Marfan's syndrome. This disorder shows a high degree of clinical variability both between and within families. Each family appears to have a unique mutation in the fibrillin gene, which precludes the routine use of mutation screening for presymptomatic diagnosis of the disorder. The goal of this study was to develop a widely applicable method of molecular diagnosis. METHODS: We used three newly characterized intragenic sites of normal DNA repeat-sequence variation (i.e., polymorphisms) as markers to follow the inheritance pattern of specific copies (alleles) of the fibrillin gene in multiple kindreds with various clinical features of Marfan's syndrome. RESULTS: The polymorphic markers allowed identification of the particular copy of the fibrillin gene that cosegregated with Marfan's syndrome in 13 of the 14 families tested. In 11 families a definite presymptomatic diagnosis of Marfan's syndrome could be made in family members who had only equivocal manifestations of the disorder. In two other families, some family members demonstrated either classic Marfan's syndrome or a milder but closely related phenotype. The copy of the fibrillin gene that cosegregated with classic Marfan's syndrome was not inherited by family members with the latter, atypical, form of the disease. These milder phenotypes, previously diagnosed as Marfan's syndrome, were not associated with aortic involvement. CONCLUSIONS: These results document the usefulness of novel polymorphic DNA repeat sequences in the presymptomatic diagnosis of Marfan's syndrome. Our findings also demonstrate that the various clinical phenotypes seen in selected families may be due not to single fibrillin mutations, but rather to different genetic alterations. These findings underscore the need for a modification of the current diagnostic criteria for Marfan's syndrome in order to achieve accurate risk assessment. PMID- 8008029 TI - Langerhans'-cell histiocytosis (histiocytosis X)--a clonal proliferative disease. AB - BACKGROUND: The lesions of Langerhans'-cell histiocytosis (histiocytosis X), a proliferative histiocytic disorder of unknown cause, contain histiocytes similar in phenotype to dendritic Langerhans' cells. The disease ranges in severity from a fatal leukemia-like disorder to an isolated lytic lesion of bone. Intermediate forms of the disease are usually characterized by multiorgan involvement, diabetes insipidus, and a chronic course. METHODS: To determine whether Langerhans' histiocytosis is a polyclonal reactive disease or a clonal disorder, we used X-linked polymorphic DNA probes (HUMARA, PGK, M27 beta[DXS255], and HPRT) to assess clonality in lesional tissues and control leukocytes from 10 female patients with various forms of the disease. Lymphoid clonality was also assessed by analysis of rearrangements at immunoglobulin and T-cell-receptor gene loci. RESULTS: The HUMARA assay detected clonal cells in the lesions of 9 of the 10 patients: 3 patients had acute disseminated disease, 3 had unifocal disease, and 3 had intermediate forms. The percentage of clonal cells closely approximated the percentage of CD1a-positive histiocytes in each lesion. Clonality was also confirmed in two of nine cases with the PGK or M27 beta probe. Extreme constitutional lyonization precluded assessment of clonality in the 10th case. Lymphoid clonality was ruled out in all cases. CONCLUSIONS: The detection of clonal histiocytes in all forms of Langerhans'-cell histiocytosis indicates that this disease is probably a clonal neoplastic disorder with highly variable biologic behavior. Thus, genetic mutations that promote clonal expansion of Langerhans' cells or their precursors may now be identified. PMID- 8008030 TI - Images in clinical medicine. Malignant melanoma. PMID- 8008031 TI - The use of high-efficiency particulate air-filter respirators to protect hospital workers from tuberculosis. A cost-effectiveness analysis. AB - BACKGROUND: After outbreaks of multidrug-resistant tuberculosis, the Centers for Disease Control and Prevention proposed the use of respirators with high efficiency particulate air filters (HEPA respirators) as part of isolation precautions against tuberculosis, along with a respiratory-protection program for health care workers that includes medical evaluation, training, and tests of the fit of the respirators. Each HEPA respirator costs between $7.51 and $9.08, about 10 times the cost of respirators currently used. METHODS: We conducted a cost effectiveness analysis using data from the University of Virginia Hospital on exposure to patients with tuberculosis and rates at which the purified-protein derivative (PPD) skin test became positive in hospital workers. The costs of a respiratory-protection program were based on those of an existing program for workers dealing with hazardous substances. RESULTS: During 1992, 11 patients with documented tuberculosis were admitted to our hospital. Eight of 3852 workers (0.2 percent) had PPD tests that became positive. Five of these conversions were believed to be due to the booster phenomenon; one followed unprotected exposure to a patient not yet in isolation; the other two occurred in workers who had never entered a tuberculosis isolation room. These data suggest that it will take more than one year for the use of HEPA respirators to prevent a single conversion of the PPD test. Assuming that one conversion is prevented per year, however, it would take 41 years at out hospital to prevent one case of occupationally acquired tuberculosis, at a cost of $1.3 million to $18.5 million. CONCLUSIONS: Given the effectiveness of currently recommended measures to prevent nosocomial transmission of tuberculosis, the addition of HEPA respirators would offer negligible protective efficacy at great cost. PMID- 8008032 TI - Thyroxine therapy. AB - The availability of sensitive thyrotropin assays allows effective biochemical monitoring of both replacement and suppressive therapy with thyroxine. Whatever target organ is examined, there is tissue thyrotoxicosis if the serum thyrotropin concentration is low, even if the serum triiodothyronine and thyroxine concentrations are normal. Although suppression of thyrotropin secretion is recommended in the treatment of patients with thyroid carcinoma, the aim of thyroxine-replacement therapy in patients with primary hypothyroidism should be to maintain the serum thyrotropin concentration in the normal range. The most convincing argument for the treatment of subclinical hypothyroidism is progression to overt hypothyroidism at a rate of 5 to 20 percent per year. PMID- 8008033 TI - Clinical research--what should the public believe? PMID- 8008034 TI - DNA repeats--a treasury of human variation. PMID- 8008035 TI - The tyranny of health. PMID- 8008036 TI - Treating cancer pain. PMID- 8008037 TI - Treating cancer pain. PMID- 8008038 TI - Treating cancer pain. PMID- 8008039 TI - Practice Profiles. PMID- 8008040 TI - Practice Profiles. PMID- 8008041 TI - Familial occurrence of neurocardiogenic syncope. PMID- 8008042 TI - Situs inversus? PMID- 8008043 TI - The last well person. PMID- 8008044 TI - Agaricus bisporus: an assessment of its carcinogenic potency. AB - This assessment focuses on the concentrations of some chemicals present in the Agaricus bisporus mushroom, the cancer-inducing doses of these chemicals or mushroom used in the animal experiments, the total amounts of these chemicals or mushroom needed to induce cancer in these mice, and the estimated total amounts of these chemicals or mushroom needed to induce cancer in humans. By adding the estimated amounts of chemicals needed to induce cancer and by comparing it with the amount of raw mushroom needed to induce the same effect, it becomes obvious that we have accounted for less than 2% of the carcinogenic components of the Agaricus bisporus mushroom. Since some unavailable data handicapped this assessment, it should be regarded as tentative and subject to further adjustment. PMID- 8008045 TI - Production of tremorgenic mycotoxins by isolates of Aspergillus fumigatus from sawmills in Sweden. AB - One hundred and six strains of A. fumigatus were isolated from 21 sawmills in Sweden, and 73 of these strains were examined for production of fumitremorgen B and verruculogen (tremorgenic mycotoxins) on YES-medium using thin layer chromatography (TLC). Twenty-three strains (32%) were tremorgen producers and 50 strains (68%) were non-producers. Tremorgenic mycotoxins were detected in conidia of seven A. fumigatus strains. The amount of toxin varied between 0.6-8.0 microgram/10(8) conidia (mean value 2.3 micrograms/10(8) conidia, equivalent with 0.18%). No production of the mycotoxin gliotoxin was detected in 6 strains of A. fumigatus. No tremorgens were detected during mould growth on wood substrates, in spite of the use of different wood species (Scots pine, Pinus sylvestris: Norway spruce, Picea abies and birch, Betula spp.), dried versus non-dried wood, bark (pine), leached wood, and wood after various sterilization methods. PMID- 8008046 TI - Alanine is a precursor in the biosynthesis of fumonisin B1 by Fusarium moniliforme. AB - The biosynthesis of fumonisin B1 by Fusarium moniliforme was studied in liquid culture. Stable isotope labeled alanine was added as a precursor to static and shaken cultures of F. moniliforme. Incorporation of 13C and 2H labeled L-alanine into fumonisin B1 was measured by GC-MS. Under static culture conditions, 20.8 micrograms ml-1 of FB1 were produced with a 5.5% level of incorporation of intact, labeled alanine into fumonisin B1. Under shake culture conditions, much higher levels of fumonisin B1 were produced with levels reaching 159-240 micrograms ml-1 by 21 days after culture initiation. A lower level of alanine incorporation, from 1.1-1.4%, was observed under these conditions. Under shake conditions, incorporation of labeled alanine was reduced because of the rapid metabolism of these cultures combined with the high level of fumonisin B1 production resulted in rapid turnover of the added, labeled alanine and reduced percentage of incorporation. The evidence presented indicates that alanine is incorporated intact into fumonisin B1. PMID- 8008047 TI - When will cigarettes be smoked out? PMID- 8008048 TI - Report prompts US to enter talks on new split of AIDS patent royalties. PMID- 8008049 TI - Television appeal funds genetics institute. PMID- 8008050 TI - Allain loses appeal and faces threat of new charges. PMID- 8008051 TI - FDA claims nicotine levels were manipulated. PMID- 8008052 TI - Deaths bring clinical trials under scrutiny in Japan. PMID- 8008053 TI - Rome 'could host European mouse laboratory'. PMID- 8008054 TI - Malaria and AIDS. PMID- 8008055 TI - Vatican error? PMID- 8008056 TI - ORI should stay. PMID- 8008057 TI - Tumour diagnosis. PMID- 8008058 TI - Wrong committees axed? PMID- 8008059 TI - Prospecting for drugs in ancient texts. AB - The mass screening of plants in the search for new drugs is vastly expensive and inefficient. It would be cheaper and perhaps more productive to re-examine plant remedies described in ancient and mediaeval texts. PMID- 8008060 TI - Evolutionary biology. Parasites and polymorphisms. PMID- 8008061 TI - Driven around the bend in Scotland. PMID- 8008062 TI - Glia and neurons in dialogue. PMID- 8008063 TI - Sex hormone response to alcohol. PMID- 8008064 TI - Heading detection from optic flow. PMID- 8008065 TI - Statue enigma. PMID- 8008066 TI - Where we look when we steer. AB - Steering a car requires visual information from the changing pattern of the road ahead. There are many theories about what features a driver might use, and recent attempts to engineer self-steering vehicles have sharpened interest in the mechanisms involved. However, there is little direct information linking steering performance to the driver's direction of gaze. We have made simultaneous recordings of steering-wheel angle and drivers' gaze direction during a series of drives along a tortuous road. We found that drivers rely particularly on the 'tangent point' on the inside of each curve, seeking this point 1-2 s before each bend and returning to it throughout the bend. The direction of this point relative to the car's heading predicts the curvature of the road ahead, and we examine the way this information is used. PMID- 8008067 TI - Specificity and flexibility in thymic selection. AB - During positive selection, developing thymocytes are rescued from programmed cell death by T-cell receptor (TCR)-mediated recognition of major histocompatibility complex (MHC) molecules. MHC-bound peptides contribute to this process. Recently we identified individual MHC-binding peptides which can induce positive selection of a single TCR. Here we examine peptide fine specificity in positive selection. These data suggest that a direct TCR-peptide interaction occurs during this event, and strengthens the correlation between selecting peptides and TCR antagonists. Certain positively selecting peptides are weakly antigenic. We demonstrate that thymocytes 'educated' on such a peptide are specifically non responsive to it and have decreased CD8 expression levels. Similar reduction of CD8 expression on mature T cells converts a TCR agonist into a TCR antagonist. These data indicate that thymocytes may maintain self-tolerance towards a positively selecting ligand by regulating co-receptor expression. PMID- 8008068 TI - Negative feedback regulation of IgE synthesis by murine CD23. AB - Immunoglobulin E is found in nanogram amounts in normal human and mouse serum. It is increased during parasitic infestations and mediates allergy. CD23, the low affinity receptor for IgE (Fc epsilon RII), has been proposed as an important regulator of IgE synthesis. The type-II transmembrane lectin CD23 is expressed in the mouse on B cells and follicular dendritic cells. In humans there are two forms of CD23 which differ in their intracellular amino-terminal 6/7 amino acids; expression of the A-form corresponds to that of murine CD23, whereas the B-form is also found on T and other haematopoietic cells. CD23 has been implicated in cellular adhesion, antigen presentation, as a growth and differentiation factor for human B, T and plasma cells, and as a signal transduction molecule (reviewed in refs 3, 8). Here we disrupt the gene coding for murine CD23 (ref. 9) to clarify the role of CD23 in vivo and find that B- and T-cell development is normal in these CD23-deficient mice. Immune responses to the helminth Nippostrongylus brasiliensis are unaffected. In contrast, immunization with thymus-dependent antigens leads to increased and sustained specific IgE antibody titres compared with controls. Formation of germinal centres is normal. These results suggest that murine CD23 acts as a negative feedback component of IgE regulation. PMID- 8008070 TI - Functional dissection of the yeast Cyc8-Tup1 transcriptional co-repressor complex. AB - DNA-binding repressor proteins mediate regulation of yeast genes by cell type (Mcm1/alpha 2 and a1/alpha 2), glucose (Mig1) and oxygen (Rox1) (refs 1-4 respectively). An unusual feature of all these regulatory pathways is that transcriptional repression requires two physically associated proteins that do not bind DNA Cyc8(Ssn6) and Tup1. The Cyc8-Tup1 complex has been proposed to be a co-repressor that is recruited to target promoters by pathway-specific DNA binding proteins, but the specific functions of the individual proteins are unknown. Here we show that when it is bound upstream of a functional promoter through the LexA DNA-binding domain, Tup1 represses transcription in the absence of Cyc8. Deletion analysis indicates that Tup1 contains at least two non overlapping transcriptional repression regions with minimal primary sequence similarity, and a separable Cyc8-interaction domain. These Tup1 domains, which do not include the beta-transducin motifs, are necessary and partially sufficient for Tup1 function. We suggest that Tup1 performs the repression function of the Cyc8-Tup1 co-repressor complex, and that Cyc8 serves as a link with the pathway specific DNA-binding proteins. PMID- 8008069 TI - A mammalian protein targeted by G1-arresting rapamycin-receptor complex. AB - The structurally related natural products rapamycin and FK506 bind to the same intracellular receptor, FKBP12, yet the resulting complexes interfere with distinct signalling pathways. FKBP12-rapamycin inhibits progression through the G1 phase of the cell cycle in osteosarcoma, liver and T cells as well as in yeast, and interferes with mitogenic signalling pathways that are involved in G1 progression, namely with activation of the protein p70S6k (refs 5, 11-13) and cyclin-dependent kinases. Here we isolate a mammalian FKBP-rapamycin-associated protein (FRAP) whose binding to structural variants of rapamycin complexed to FKBP12 correlates with the ability of these ligands to inhibit cell-cycle progression. Peptide sequences from purified bovine FRAP were used to isolate a human cDNA clone that is highly related to the DRR1/TOR1 and DRR2/TOR2 gene products from Saccharomyces cerevisiae. Although it has not been previously demonstrated that either of the DRR/TOR gene products can bind the FKBP-rapamycin complex directly, these yeast genes have been genetically linked to a rapamycin sensitive pathway and are thought to encode lipid kinases. PMID- 8008071 TI - Three-dimensional structure of beta-galactosidase from E. coli. AB - The beta-galactosidase from Escherichia coli was instrumental in the development of the operon model, and today is one of the most commonly used enzymes in molecular biology. Here we report the structure of this protein and show that it is a tetramer with 222-point symmetry. The 1,023-amino-acid polypeptide chain folds into five sequential domains, with an extended segment at the amino terminus. The participation of this amino-terminal segment in a subunit interface, coupled with the observation that each active site is made up of elements from two different subunits, provides a structural rationale for the phenomenon of alpha-complementation. The structure represents the longest polypeptide chain for which an atomic structure has been determined. Our results show that it is possible successfully to study non-viral protein crystals with unit cell dimensions in excess of 500 A and with relative molecular masses in the region of 2,000K per asymmetric unit. Non-crystallographic symmetry averaging proved to be a very powerful tool in the structure determination, as has been shown in other contexts. PMID- 8008072 TI - Cancer screening. PMID- 8008073 TI - Continuing controversy: doctors vs. lawyers. PMID- 8008074 TI - Continuing controversy: doctors vs. lawyers. PMID- 8008075 TI - An athlete dying young. Arrythmogenic right ventricular dysplasia. PMID- 8008076 TI - Clearing athletes for participation in sports. The North Carolina Medical Society Sports Medicine Committee's recommended examination. AB - The North Carolina Medical Society's Medicine Committee has reviewed current U.S. literature on preparticipation examinations and adopted a documentation form that fits the specific needs of our state. In spite of a recently published comprehensive monograph on preparticipation physical evaluation, no national consensus exists about whether comprehensive preparticipation exams or brief, focused examinations are better. With this in mind, we limited medical history questions to those determined by previous studies to identify specific problems. Also included are evaluations of blood pressure, musculoskeletal, and cardiovascular systems since studies have shown significant yield from these. The same studies find little benefit from the remainder of a comprehensive physical assessment. The recommended evaluation represents a minimal standard and addresses the core areas likely to prevent athletes from participating safely in sports. No recommended exam could cover all issues that affect school-age athletes--health prevention, adolescent development, general medical care, and psychological stresses--but physicians can use the recording form as a starting point and incorporate a more extensive evaluation into the assessment of athletes found to be at increased risk. Consistent use of this examination should promote better detection of sport-specific risks related to cardiovascular disorders, asthma, musculoskeletal problems, concussions, heat-related problems, and general medical problems. The Sports Medicine Committee wants to promote physical activity. Before disqualifying athletes physicians should remember that the disqualification rate in published studies averages only 1%. When questions about the need for disqualification arise, consultation may be advisable.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8008077 TI - Hypothyroidism. The varied manifestations of a common disorder. PMID- 8008078 TI - Families in pain. PMID- 8008079 TI - The pattern and cost of hospital care for persons with HIV/AIDS in Guilford County, NC, 1987-1991. PMID- 8008080 TI - Screening for human immunodeficiency virus in physicians. Who should we test and what will it cost. PMID- 8008081 TI - Screening for melanoma. "Here's looking at you, kid". PMID- 8008082 TI - Adult patients with congenital heart disease. AB - Adult patients with congenital heart disease present complex problems that require individualized management. Unfortunately, few physicians who care for adults with congenital heart disease have received adequate specific training to deal with their problems. Pediatric cardiologists who are familiar with congenital heart disease often refer patients to adult cardiologists after adolescence. And adult cardiologists have not traditionally had much training or experience in dealing with congenital heart disease. The cardiac needs of these patients are often best managed through the collaborative efforts of adult and pediatric cardiologists, cardiac surgeons, specialized nurse clinicians, and social workers. Of course, it is crucial to their optimal care that there be involvement of a primary care physician who can help with their many medical, surgical, and psychosocial problems. PMID- 8008083 TI - HCFA asking for proposals to begin ESRD capitated payment model. PMID- 8008084 TI - Elderly dialysis patients: some do quite well. PMID- 8008085 TI - Nephrologists should be primary care physicians. PMID- 8008087 TI - IDPN: HCFA continues to reimburse, but will strengthen enforcement of regulations. PMID- 8008086 TI - Renal Systems outlines path leading to lawsuit. PMID- 8008088 TI - QA assessment, infection control, ethical issues highlight CA dialysis meeting. PMID- 8008089 TI - The changing specialty of nephrology nursing over the past 25 years. PMID- 8008090 TI - Nephrology nursing in the future. Changing the way we manage. PMID- 8008092 TI - Technicians tackle issues in Dallas. Excellence through education: a smart investment. PMID- 8008091 TI - Nephrology nursing in the future. How will clinical nurses provide care? PMID- 8008093 TI - Technicians tackle issues in Dallas. NANT: the past, present, and future. PMID- 8008094 TI - For technicians/technologists, continuing education still scarce but improving. PMID- 8008095 TI - Nephrologists should be the primary care physician for minority, poor dialysis patients. PMID- 8008096 TI - Encouragement, early intervention, and self care are key. PMID- 8008097 TI - NMC, ProPAC discuss alternative methods for EPO reimbursement. PMID- 8008098 TI - Economics of managed competition and consequences to nurses: Part I. AB - Managed competition is an economic strategy to reform the health care system by stimulating price competition and quality improvement. If adopted, it will fundamentally alter the clinical practice and economic environments of nurses. PMID- 8008099 TI - Innovation in nursing: a benefit/cost analysis. AB - This study found that costs of implementing projects aimed at improving nurse recruitment and retention vary substantially. At 37 hospitals the costs ranged from a mean of $1,029 per bed for shared governance to $8,399 per bed for computer projects. For a typical 30-bed unit implementing a non-computer project, an average of 1,800 hours of personnel time was devoted to implementation. In most cases, hospitals found that the projects took more resources than expected to get off the ground. The benefit/cost results indicate that the potential annual savings in hospital operation costs associated with reduced length of stay were approximately $3,015 for each $1,000 of one-shot implementation costs spent per bed. PMID- 8008100 TI - Shared governance: innovation or imitation? AB - Is nursing shared governance an innovation or merely an imitation of other organizational governances? A simple determination is confused by the euphemisms applied to similar governance forms and the simultaneous occurrence of related concepts like participation and decentralization. In the absence of a common model, anecdotal literature suggests that the implementation of shared governance in specific hospitals contributes to further innovation in governance. PMID- 8008101 TI - Nursing management innovations: a need for systematic evaluation. AB - While emphasis in nursing is placed on research on clinical interventions, there has been little attention to the equally important management interventions. The concept of a management intervention or innovation is introduced here and five types of management innovations in nursing are identified. An overview of the research base for four of the innovations demonstrates the need for systematic evaluation. PMID- 8008102 TI - Shed that cocoon and fly! PMID- 8008103 TI - The impact of patient point-of-view pharmacy delivery on labor and quality. AB - A 37-bed surgical unit in a Midwestern Medical Center was the site of 30 day trials of three methods of medication delivery: (a) traditional medication cart, (b) patient point-of-view (PPOV1) delivery of regularly ordered medication by a pharmacy technician to the nurse server once a day, and (c) patient point-of-view (PPOV2) delivery of all medications (including stats and i.v.s) to the nurse server hourly between 0700 and 2300 hours. The purpose of this trial was to determine the effects of two alternative pharmacy delivery strategies on labor costs, use of professional nurses' time, and ten quality indicators related to medication administration. PMID- 8008104 TI - An interview with Mary Beth Pais. Interview by Connie R Curran. AB - Mary Beth Pais, MNEd, RN, ONC, the recipient of the 1993 Nursing Economic$ Excellence Award, is clinical nurse manager, University of Pittsburgh Medical Center, Montefiore University Hospital, Pittsburgh, PA. In this interview she discusses the challenges and lessons learned from developing a work redesign model, critical paths, and the implementation of a pre-operative patient assessment and education program. PMID- 8008105 TI - Comparative cost analysis of surgical procedures in an ambulatory eye center. AB - At the Medical Center of Central Massachusetts, a 500-bed acute and ambulatory teaching hospital, a comparative analysis of labor and supply costs was initiated. The multidisciplinary approach resulted in collaboration, support, and ultimately in financial savings to the institution. PMID- 8008106 TI - The nurse manager in an integrated health system. PMID- 8008107 TI - The plan will not work. PMID- 8008108 TI - Plotting the major health care reform proposals. PMID- 8008109 TI - The theory of cooperation and the nurse manager's challenge. PMID- 8008110 TI - Mirror, mirror on the wall.... PMID- 8008111 TI - A vote for the single-payer system. PMID- 8008112 TI - Dispiriting lack of leverage. PMID- 8008113 TI - Do you work for a good hospital? How do you know? PMID- 8008114 TI - An interview with Phyllis Ethridge. Interview by Neale Miller. AB - Phyllis Ethridge, MS, RN, FAAN, CNAA, is vice president, patient care services, Carondelet St. Mary's Hospital & Health Center, Tucson, AZ. In this interview she discusses challenges for nurse executives, a nursing HMO, chronic patients, and team work. PMID- 8008115 TI - Health care reform: implications for staff development. AB - Staff development is an accepted and essential part of health care and nursing. Understanding how the principles of health care reform--simplicity, quality, savings, and choice--interact within the framework of staff development sets the stage for understanding the professional and business opportunities awaiting staff development educators. PMID- 8008116 TI - Economics of managed competition and consequences to nurses: Part II. AB - Nurses must anticipate and prepare for the considerable threats and substantial opportunities that will evolve if a relatively pure form of managed competition emerges as the economic strategy guiding health care reform. PMID- 8008117 TI - Use of unlicensed assistive personnel by hospitals. PMID- 8008118 TI - A review of ambulatory care analysis. AB - Acute care is shifting from the hospital to ambulatory settings. Research continues on the effects of this change on patient requirements. A comprehensive literature review surrounding these issues is provided. PMID- 8008119 TI - Visioning: an important management tool. AB - Visioning is a powerful process that assists us in creating a picture of an ideal future. A vision is a dream, personally created, of how we would like our world to be. In sharing our visions we find common ground and a sense of connection. Today, in an unprecedented way, nurses at all levels are expected to exhibit leadership in setting direction for nursing practice. Assisting nurses to create and share their vision of the future is a mark of transformational leadership. It is an act of empowerment and an expression of caring. PMID- 8008120 TI - Stat nursing--alive and well. PMID- 8008121 TI - [Reflex sympathetic dystrophy also in children]. PMID- 8008122 TI - [Transfusion medicine]. PMID- 8008123 TI - [Transfusion of fresh frozen plasma and other plasma preparations]. PMID- 8008124 TI - [Prevention of immunization against erythrocyte antigens c, E and K caused by blood transfusion]. PMID- 8008125 TI - [3-week traction with 3-week spica-cast immobilization is as good as 6-week traction, and much cheaper]. AB - OBJECTIVE: To gain insight into the clinical en economic results of the treatment of femoral shaft fractures in children by means of traction for 3 weeks and spica immobilization for 3 weeks as an outpatient in comparison with traction for 6 weeks. DESIGN: Retrospective. SETTING: Sophia children's hospital in Rotterdam. METHOD: Between 1981 and 1989, 278 children were admitted because of a femoral shaft fracture. This follow-up study concerned 229 children of whom 139 were treated by means of 6 weeks' traction (group 1) and 90 received the combination treatment (group 2). The two groups were comparable with regard to age, sex, cause, type and site of the fracture. RESULTS: All fractures healed, complications were rare and equally divided between the two groups. There was no significant difference between the two groups with regard to shortening and angulation of bone fragments. The mean duration of hospital stay was almost 47 days in group 1 as against 22 days in group 2, leading to a reduction of Dfl. 19,500.--in hospitalization costs per child. CONCLUSION: The results of treatment of femoral shaft fractures by means of traction in combination with spica immobilization equal those of 6 weeks' traction. The shortened duration of hospital stay leads to a considerable reduction in costs. PMID- 8008126 TI - [Changes in drug use during a stay in a psychogeriatric nursing home]. AB - OBJECTIVE: To describe the changes in drug intake during institutionalization in a Dutch psychogeriatric nursing home. SETTING: Psychogeriatric nursing home Joachim en Anna in Nijmegen, the Netherlands. DESIGN: Retrospective analysis of medical charts. PATIENTS AND METHODS: In 390 patients drug intake (sixteen drug groups) at admission, after six weeks, at half yearly intervals and on the day of death was recorded in a longitudinal fashion, as were side effects. Increase or decrease in drug intake was tested by means of linear regression analysis. RESULTS: After an initial decrease there was a gradual increase in mean drug intake during institutionalization. Laxatives and to a lesser degree drugs for the respiratory tract and heart were mostly responsible for this increase. In the other groups no change or even decrease was noted. The degree of dependency and the type of dementia had an influence on these changes. At the day of death analgesics, morphinomimetics and bronchodilators were the most frequent drugs. Neuroleptics caused most of the side effects observed. CONCLUSION: Prescription of laxatives is mostly responsible for the increase in mean drug intake in this Dutch psychogeriatric nursing home. PMID- 8008128 TI - [Value of treatment of low-grade glioma still controversial]. AB - There is debate in the literature on the treatment of low-grade glioma, especially regarding the role of radiotherapy. Several retrospective analyses have demonstrated longer survival and delayed tumour recurrence in patients treated with radiotherapy. However, radiotherapy may bring about adverse events, especially in long-term survivors. In four patients, a women of 54 and three men of 51, 31 and 16 years old, a low-grade glioma was diagnosed. In three, expectative therapy, combined with antiepileptic drugs, or with radiotherapy and partial tumour resection (n = 1) led to a period of many years without symptoms. In the fourth, total tumour resection followed by radiotherapy did not prevent recurrence of the tumour and death of the patient. PMID- 8008127 TI - [A study of dysfunction in specialists]. AB - OBJECTIVE: To determine the volume of dysfunctioning of medical specialists. DESIGN: Descriptive. SETTING: 21 hospitals in the Dutch province of Noord Holland. METHODS: After introductory conversations with key figures in this field, the Health Inspection visited 21 hospitals in Noord-Holland. Managers or medical staff had previously returned written questionnaires. RESULTS: According to medical staff and management 93 of 2000 specialists had been found to dysfunction, over a period of 5 years. Symptoms of dysfunctioning were lack of social skills, mistakes in medical judgment and inability to work in a team. Authorities complained of a lack of subtle sanction possibilities. CONCLUSION: Hospital boards are inclined to cover up dysfunctioning of specialists in a 'conspiracy of silence'. More effective sanction possibilities are at hand, since the new legislation, although prevention is preferred. Proposals to intensify application procedures and evaluate medical functioning are not followed. Investigating dysfunctioning in other professions, like general practice and dental care is advisable. PMID- 8008129 TI - [HIV-positive blood donors, 1985-1993]. PMID- 8008130 TI - [Diversity of medical curricula in The Netherlands]. PMID- 8008131 TI - [Gallstones in the minor pelvis following laparoscopic cholecystectomy]. PMID- 8008132 TI - [A female patient with a vesico-uterine fistula]. PMID- 8008133 TI - [The Society Medical-Dental Interaction: a symposium on antibiotic prophylaxis]. PMID- 8008134 TI - [Surgical orthodontics in the correction of facial abnormalities; not always without problems]. PMID- 8008135 TI - [That Prozac feeling]. PMID- 8008136 TI - [Dental surgery possibilities for the edentate patient]. PMID- 8008137 TI - [Irritation hyperplasia in wearers of dental prostheses]. PMID- 8008139 TI - [Mortality in patients with dementia following admission to a nursing home; a 10 year analysis]. AB - OBJECTIVE: To identify factors that have an effect on mortality after admission of nursing home patients with dementia and to investigate changes in mortality and patients' characteristics throughout ten years of patient admittance. SETTING: Psychogeriatric nursing home 'Joachim en Anna', Nijmegen, the Netherlands. DESIGN: Retrospective analysis of medical charts. PATIENTS AND METHODS: In 890 patients, admitted between 1980 and 1989, the diagnosis of dementia was determined by means of the DSM-III-R criteria and the ischaemia scale of Hachinski. Comorbid conditions were classified by the ICHPPC-2-defined. Severity of dementia was expressed by a rating scale for elderly patients. Survival analysis was done by using product-limit estimates and Cox proportional hazards model. RESULTS: The overall 2-year survival rate after admission was 43%, 30% for men and 49% for women. The results of proportional hazards modelling indicated that gender, age at admission, type of dementia, rate of dependency and some comorbid conditions had a statistically significant influence on mortality. Between 1980 and 1989 there were no significant changes in mortality nor in patients' characteristics. CONCLUSION: Mortality after admission to this psychogeriatric nursing home is determined by multiple factors. Based on these factors the prognosis with respect to survival can be estimated. PMID- 8008138 TI - [Indicators for progression of dementia in nursing home patients]. AB - OBJECTIVE: To investigate the relationship of progression of dementia with patients' characteristics, comorbidity and psychotropic drug use in nursing home patients. SETTING: Psychogeriatric nursing home 'Joachim en Anna', Nijmegen, the Netherlands. DESIGN: Retrospective analysis of medical charts. PATIENTS AND METHODS: In 645 patients, admitted between 1980 and 1989, progression of dementia was expressed by means of a functional status questionnaire developed in the nursing home. Severity of dementia at entry was expressed by a rating scale for elderly patients. Comorbid conditions were classified according to the ICHPPC-2 defined. Psychotropic drug use was expressed as the ratio between days of usage and days of the observation period. Statistical analysis was done by analysis of (co)variance and regression analysis. RESULTS: In univariate as well as in multivariate analysis progression of dementia was related to time spent in the nursing home, severity of dementia at entry and comorbidity and to a lesser degree psychotropic drug use. Patients who stayed for a short time and had a high frequency of concomitant diseases and psychotropic drug use had a faster progression of dementia. Gender, age at entry and type of dementia were of no significance. The factors mentioned, however, accounted for only 20% of the variance. CONCLUSION: Progression of dementia is a complex process which can only partly be explained by the factors mentioned. Nursing home physicians nevertheless should consider these factors when predicting progression. PMID- 8008140 TI - [Strongyloides infections in former prisoners of war in South-East Asia in the second World War; additional information from serological diagnosis]. AB - OBJECTIVE: To analyse the efficacy of ELISA serology in patients with Strongyloides infection acquired during World War II and maintained through repeated autoinfection. DESIGN: Descriptive. SETTING: Laboratory of Parasitology, Faculty of Medicine, Leiden, the Netherlands. METHODS: Parasitological and clinical data on 193 ex-prisoners of war (South-east Asia) were presented previously (1990) by Verburg and De Geus. ELISA using L-3 S. ratti antigen was carried out with sera of these patients and the results were compared with those of repeated stool examinations using Baermann's method. RESULTS: All subjects harbouring larvae in repeated stool examinations (26) were positive in serology. In 21 out of 167 patients in whom no larvae could be demonstrated, specific antibodies were detected. Anamnestic information together with data on eosinophilia and IgE levels suggested that the majority of these subjects were actually infected. The serological prevalence of infection with Strongyloides stercoralis was 33% for those imprisoned in Burma and 4% for those who were prisoners of war in the former Netherlands East Indies. CONCLUSION: In the group of subjects studied, in whom Strongyloides infection was apparently maintained through a process of autoinfection for a period of over 40 years, serology appears a sensitive and specific diagnostic tool. Larvae could be detected in no more than 26 out of 47 serologically positive subjects. PMID- 8008141 TI - [Compression under ultrasonic control as treatment of a pseudo-aneurysm following catheterization in the groin]. AB - A false aneurysm is a well known complication after catheterisation. It is increasingly seen as a result of the increase of cardiological intervention treatment. In the past the classical treatment was surgery, nowadays a expectative management is the more frequently chosen alternative. A new treatment consists of compression under color Doppler ultrasonography control. This treatment frequently leads to direct thrombosis of the false aneurysm and can be carried out on an outpatient basis. PMID- 8008142 TI - [Severe hyponatremia, possibly due to inappropriate antidiuretic hormone secretion, during use of the antidepressant fluoxetine]. AB - In a 78-year-old female with hyponatraemia, the syndrome of inappropriate ADH secretion as a side effect of fluoxetine, a relatively new antidepressive drug, was tentatively diagnosed. In the literature 14 cases of this adverse reaction have been described. One should be careful when prescribing fluoxetine to elderly persons, notably when a diuretic is prescribed as well. PMID- 8008143 TI - [Curriculum 2000: patient-oriented instruction at the medical faculty groningen]. PMID- 8008144 TI - [Stricter examination: the final hours of the WAO? (Law for Work Disability Insurance)]. PMID- 8008145 TI - [Invasive aspergillosis: epidemiology, diagnosis and therapy]. PMID- 8008146 TI - [Attention deficit disorder with hyperactivity]. PMID- 8008147 TI - [Atherosclerosis also caused by local vascular inflammation]. PMID- 8008148 TI - Historical perspective of Rh disease in Nebraska (1973-1982). Part II. Profile of Rh negative women experiencing a fetal death. PMID- 8008149 TI - Isolated systolic hypertension: a different kind of high blood pressure. AB - Isolated systolic hypertension is a distinct disease entity associated with serious morbidity and mortality, in particular, stroke. The mechanism of systolic hypertension appears to be a reduction in arterial compliance. Identification of patients at greatest risk is paramount. A simple nonpharmacologic or pharmacologic intervention can decrease isolated systolic hypertension, enhance quality of life and prevent major cardiovascular and cerebrovascular complications. PMID- 8008150 TI - Impaired nurse program changes name and expands focus. PMID- 8008151 TI - DNR: a moral decision. PMID- 8008152 TI - Power and politics: do nurse executives know how to play the game? PMID- 8008153 TI - Mixed oligoastrocytomas: a survival and prognostic factor analysis. AB - Seventy-one patients with supratentorial mixed oligoastrocytomas underwent surgery only (5 patients) or surgery with postoperative radiation therapy (66 patients) between 1960 and 1982. The median survival for these 71 patients was 5.8 years and the 5-, 10-, and 15-year survival rates were 55, 29, and 17%, respectively--values significantly different from those of an age- and sex matched normal reference population. Uni- and multivariate survival analyses were applied to 14 possible prognostic factors, including the following: patient factors--age, sex, and seizures; tumor factors--site, size, side, computed tomographic enhancement, and calcification; pathological factors--tumor grade and dominant cellular component; and treatment factors--extent of surgical resection, lobectomy, and radiation dose and field. Of these factors, tumor grade, as determined by the Kernohan method, was the most strongly associated with survival. The 60 patients with Grades 1 and 2 tumors had a median survival of approximately 6.3 years and 5- and 10-year survival rates of 58% and 32%, respectively, compared with 2.8 years (36 and 9%, respectively) for the 11 patients with Grades 3 and 4 tumors. Age < 37 years, gross total resection, partial brain radiation, and radiation dose > or = 5000 cGy were other factors significantly associated with improved survival in both uni- and multivariate models. Three of five patients not receiving postoperative radiation therapy experienced tumor recurrence and died. Seven of eight patients from whom tissue was obtained at the time of tumor progression demonstrated anaplastic transformation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8008154 TI - Desmoplastic infantile gangliogliomas: an approach to therapy. AB - Desmoplastic infantile gangliogliomas are massive cystic tumors, typically occurring in the cerebral hemispheres of infants. They are remarkable pathologically for a prominent desmoplasia and, in some cases, for a cellular mitotically active component that can be readily interpreted as a malignant neoplasm. Four children less than 1 year of age were diagnosed with desmoplastic infantile gangliogliomas in the Pediatric Oncology Group infant brain tumor study (Protocol number 8633). All had been diagnosed by their respective institutions as having malignant tumors, i.e., Grade III astrocytoma, malignant meningioma, leptomeningeal fibrosarcoma, and gliosarcoma. All had increased intracranial pressure, and two had seizures. The tumors were extremely large, with one measuring 12 x 9 x 9 cm. None had evidence of metastatic disease. One patient had a gross total resection, and the other three had debulking procedures. All four children were treated with chemotherapy (cyclophosphamide, vincristine, cisplatinum, etoposide) for periods ranging from 12 to 24 months. Of those with postoperative measurable disease, one child had a complete response, one a partial response, and one had stable disease at the conclusion of chemotherapy. No child received radiation therapy. All children are alive with progression-free survivals after diagnosis of more than 36, 42, 48, and 60 months, respectively. Although desmoplastic infantile gangliomas are rare, recognition of this tumor type is essential because, despite their massive size and pathologically malignant appearance, they may have a relatively benign clinical course. If total surgical resection can be achieved, further therapy may not be indicated. In those patients in whom residual disease is present, chemotherapy appears to be an effective form of therapy.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8008155 TI - Chronic meningitis: the role of meningeal or cortical biopsy. AB - Meningeal and cortical biopsies were evaluated in 37 patients (25 men and 12 women; mean age, 54 yr) who had chronic meningitis of an unknown cause between 1985 and 1993 (the era of magnetic resonance imaging). Magnetic resonance imaging with gadolinium contrast was the most useful diagnostic imaging technique, demonstrating meningeal enhancement in 15 of 32 patients (47%). Only 2 of 32 (6%) computed tomographic scans revealed enhancement. A definitive diagnosis was made in 16 of 41 biopsies (39%), but in cases where enhancement was present on either magnetic resonance imaging or computed tomography, a diagnosis was obtained in 80% (12 of 15 cases). Only 2 of 22 biopsies (9%) from nonenhancing regions were diagnostic. Although the locations of enhancement were distributed evenly, biopsies through suboccipital and pterional craniotomies gave the highest diagnostic yields (50%). Furthermore, if the biopsies were obtained from enhancing regions, the yield of these two approaches increased to 84 and 100%, respectively. Of 18 cases in which biopsy samples were taken from both the meninges and cortex, only 1 had cortical involvement alone. The meninges were therefore diagnostic in 15 of the 16 definitive diagnostic cases (94%). Second biopsies were necessary in four cases, of which the three biopsies from enhancing regions were diagnostic. The most frequent causes of chronic meningitis were sarcoid (31%) and metastatic adenocarcinoma (25%).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8008156 TI - Tethered cord syndrome: the low-lying and normally positioned conus. AB - We have previously proposed the existence of the tethered cord syndrome in the presence of a conus medullaris in the normal position. Our 12-year series of 73 patients with the tethered cord syndrome included 13 patients in whom the spinal cord terminated at or above the L1-L2 disc space. We compare the characteristics of these 13 with those of the 60 patients whose spinal cord terminated below the L1-L2 disc space. The parameters for comparison included neurological status at presentation and follow-up, the presence of cutaneous stigmata of occult spinal dysraphism, vertebral anomalies, and others. The frequency of occurrence of each parameter in the normally positioned group was essentially the same as its occurrence in the low-lying group. PMID- 8008157 TI - Evidence for adaptive autoregulatory displacement in hypotensive cortical territories adjacent to arteriovenous malformations. Columbia University AVM Study Project. AB - We hypothesized that chronic hypotension in normal vascular territories fed by arteriovenous malformation pedicles may reset the lower limit of autoregulation and allow flow to remain constant over a lower pressure range. We studied the effect of increasing systemic mean arterial pressure (SMAP) with phenylephrine on cerebral blood flow using a novel technique. Fourteen patients undergoing 15 procedures were studied before endovascular embolization of arteriovenous malformations under neuroleptic conscious sedation. Mean pressures were transduced via a 1.5-F intracranial microcatheter, which was passed under fluoroscopic guidance into the target feeding artery. The microcatheter was positioned (unwedged) at a point that was relatively hypotensive to systemic pressure but that irrigated normal cortex on angiography; feeding mean arterial pressure (FMAP) and SMAP were recorded. A bolus of 133Xe in saline was injected into the microcatheter, and washout was recorded for 3 minutes by a scintillation detector placed over the vascular territory of the injected pedicle. SMAP was then increased approximately 25 mm Hg by phenylephrine infusion, a second bolus was given, and washout was recorded. After exclusion of the shunt spike, initial slope was calculated. The SMAP (mean +/- standard error) increased from 65 +/- 3 to 89 +/- 2 mm Hg (P < 0.0001), and FMAP increased from 46 +/- 3 to 63 +/- 3 mm Hg (P < 0.0001); cerebral blood flow did not change (40 +/- 2 to 40 +/- 2 ml/100 g per min, P = 0.9199). Dividing the cases on the basis of the baseline FMAP into a "severe" hypotensive group (FMAP = 38 +/- 2; n = 7) and a "moderate" hypotensive group (FMAP = 54 +/- 3; n = 8), cerebral blood flow did not change in either group during phenylephrine challenge. Chronic hypotension does not necessarily result in "vasomotor paralysis" with loss of the ability to vasoconstrict to acute increases in perfusion pressure. Instead, it appears to displace adaptively the lower limit of autoregulation in affected vascular territories by a shift of the autoregulatory curve to the left, conceptually analogous to the adaptive displacement seen with chronic hypertension and its treatment. PMID- 8008158 TI - Intracranial vertebral artery dissections: clinical, radiological features, and surgical considerations. AB - We reviewed 24 patients with intracranial vertebral artery dissections treated during the last 12 years. Sixteen patients were admitted with subarachnoid hemorrhage (SAH) and 8 did not have SAH. The mean age at the time of onset was 50.0 years. Male preponderance was noted. Among 21 patients with acute onset, 6 (29%) experienced prodromal neck pain and 3 (60%) of 5 SAH patients showed nuchal stiffness when examined within 6 hours of onset. The preoperative angiographical findings were uniform in SAH cases in contrast to the varied angiographical findings seen in non-SAH cases. So-called pearl and string sign was observed in most SAH cases, but the "string" was often so short and wide that the term "constriction" appeared more suitable. From intraoperative observations, the angiographical point of constriction seemed to represent the proximal or distal end of dissection. As for treatment, 19 patients underwent 20 surgeries. Trapping was performed in eight surgeries, base clipping was performed in five, and proximal clipping was performed in seven. Both trapping and base clipping prevented further bleeding, but trapping was associated with a high rate of postoperative lower cranial nerve palsy. Postoperative neurological complications were less frequent after proximal clipping, but subsequent postoperative bleeding occurred in one patient treated by this technique. The overall long-term outcome in the surgically treated cases in our series was favorable, but most patients suffered from various degrees of uncomfortable dysphagia or hoarseness for some period after surgery. It was also noted that, in half of the disabled cases, the major disability was attributable to lower cranial nerve palsy and respiratory troubles that developed postoperatively. PMID- 8008159 TI - The use of lobectomy in the management of severe closed-head trauma. AB - A retrospective review is presented of 20 patients with traumatic brain injury who were treated during the course of their illness by lobectomies either after a herniation or other significant deterioration or to reduce elevated intracranial pressure. All the patients suffered from blunt head trauma. Patient ages ranged from 19 to 59 years (average, 34 yr). The initial Glasgow Coma Scale score ranged from 3 to 15 (average, 8.2). There were 14 frontal lobectomies, 2 temporal, 3 frontal and temporal, and 1 occipital. Surgery was performed between 0 and 8 days after injury (average, 2.8). Outcome was favorable (good or moderately disabled) in 11 patients and unfavorable (severely disabled, persistently vegetative, or dead) in 9. No patients survived in a persistently vegetative state. A higher initial Glasgow Coma Scale score was positively correlated with a more favorable outcome (P < 0.03). Younger patients also showed a significant positive relationship to outcome (P < 0.0005). Better pupillary reactivity showed a significant trend toward a more favorable outcome (P < 0.04). The type of lesions identified on computed tomographic scans had no association with outcome. A lobectomy can be a useful adjuvant in the management of severe brain injury, especially in younger patients with relatively higher initial Glasgow Coma Scale scores who subsequently deteriorate or develop elevated intracranial pressure. PMID- 8008160 TI - Transdural approach to the anterior spinal canal in patients with cervical spondylotic myelopathy and superimposed central soft disc herniation. AB - We present seven patients with multilevel cervical spondylotic myelopathy and superimposed midline soft disc herniation who were treated by decompressive laminectomies of the spondylotic segments followed by transdural excision of the anteriorly located disc extrusion. There was no perioperative neurological morbidity or mortality associated with this operation, and no patients have developed postoperative kyphotic deformity with an average follow-up of 50.1 months (range, 24 to 87 mo). Two patients had full neurological recovery, whereas five patients had improvement in their preoperative neurological status. We conclude that a posterior transdural approach may offer an alternative surgical option for select patients with multilevel cervical spondylosis with superimposed midline soft disc herniation in whom multiple segment decompression plus access to the anterior spinal canal is necessary. PMID- 8008161 TI - Disco-computed tomography in extraforaminal and foraminal lumbar disc herniation: influence on surgical approaches. AB - Between January 1990 and February 1992, a total of 301 patients underwent discectomy for lumbar disc herniation; 29 had an extreme lateral herniation, i.e., foraminal or extraforaminal. The intervertebral foramen is a three dimensional area demarcated primarily by the pedicles; we call it the lateral interpedicular compartment. The extraforaminal zone is the space outside the lateral border of the pedicles. All patients were evaluated by computed tomography (CT), water soluble myelography, postmyelographic CT scanning, or magnetic resonance imaging. Fifteen patients consecutively underwent disco enhanced CT to adjust a correct diagnosis and to distinguish extraforaminal from foraminal herniation. In 10 cases of extraforaminal herniation, a selective radicular decompression with good-to-excellent clinical results was achieved by an extra-axial lateral decompression of the interpedicular compartment, with preservation of the facet joint. The operative target was the lateral aspect of the pars interarticularis and not the intertransverse space, as previously described. In two cases of both foraminal and extraforaminal herniation, the same technique was used. Fourteen patients with foraminal disc herniation and three patients with both foraminal and extraforaminal herniation underwent a standard intervertebral foraminotomy. An accurate preoperative diagnosis established by disco-CT is crucial in order to select the most suitable surgical approach. PMID- 8008162 TI - In vivo efficacy of intrathecal transferrin-Pseudomonas exotoxin A immunotoxin against LOX melanoma. AB - Neoplastic meningitis due to the dissemination of systemic cancer or primary central nervous system tumors through the cerebrospinal fluid carries a very poor prognosis. Current treatments for this disease are ineffective, and new therapeutic modalities such as immunotoxins may be beneficial. We created an animal model of human carcinomatous meningitis with LOX melanoma-derived tissue culture cells in athymic rats for testing the efficacy of intrathecal therapy with transferrin-Pseudomonas exotoxin A (Tfn-PE) immunotoxin. An injection of 5 x 10(5) LOX cells into the intrathecal space through an indwelling catheter resulted in the reproducible development of lower-extremity paraplegia at 9.24 +/ 1.77 days because of focal deposits of tumor growth adjacent to the thoracic and lumbar spinal cord. A dose of 2.5 or 5 micrograms of intrathecal Tfn-PE immunotoxin was neurotoxic and resulted in the deaths of 8 of 10 animals within 24 hours. Histological evidence of central nervous system damage was seen as hemorrhagic degeneration around the central canal or a pathological cleft at the level of the cervical spinal cord. Because no neurotoxicity was seen with 1 microgram of intrathecal Tfn-PE immunotoxin, this dose was administered in treatment experiments. Twenty-four hours after the intrathecal instillation of LOX cells, 10 animals received intrathecally either 1 microgram of Tfn-PE or phosphate-buffered saline with 0.1% human serum albumin (control group).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8008163 TI - Differentiation therapy is potentiated by chemotherapy and hyperthermia in human and canine brain tumor cells in vitro. AB - Human glioblastoma (U-87MG) and canine glioma (canine brain tumor [CBT]) cell lines were tested in vitro for their therapeutic sensitivity to sequential treatment with differentiating agents and chemotherapy or hyperthermia. Both cell lines responded to the inducer combination dibutyryl adenosine-3',5'-cyclic monophosphate/sodium butyrate by the formation of cytoplasmic processes detectable within 7 hours and attained approximately 90% morphological differentiation within 2 days of exposure. The clonogenicity of CBT and U-87MG cells gradually decreased after 1 to 7 days of exposure to the inducer combination, but this treatment alone failed to kill the cells. After the removal of the inducers, both lines dedifferentiated and the rate of clonogenesis increased. 1,3-bis-(2-Chloroethyl)-1-nitrosourea administered to CBT and U-87MG cells before or after 3 days of treatment with inducers potentiated the antiproliferative effects of the differentiating agents. Cisplatin administered to U-87MG cells enhanced the antiproliferative effect of the differentiating agents to a greater extent when added before the inducers rather than after differentiation was stimulated. The sequential treatment of CBT cells with a 44 degrees C heat pulse for 30 minutes followed by differentiating agents produced an additive potentiation of cell killing, whereas the reverse sequence did not. Hyperthermia pretreatment at 44 degrees C for 15 minutes or at 42 degrees C for 30 minutes failed to enhance the antiproliferative effects of inducing agents.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8008164 TI - Synergistic effect between intraneoplastic methotrexate and radiation on experimental intracerebral rat gliosarcoma. AB - Methotrexate (MTX) alone has a limited effect against malignant brain tumors, but we previously demonstrated a beneficial synergism between MTX and radiation therapy (XRT) against RT-9 gliosarcoma. Because the beneficial effects of that study were limited by systemic toxicity and poor brain penetration of MTX, we have continued our studies using direct intracerebral MTX therapy. Male CD-Fisher rats with intracerebrally implanted RT-9 gliosarcoma and indwelling brain tumor catheters were treated with intracerebral injections of MTX, whole-brain XRT, or a combination of both. MTX was given either as one of two "high-dose" treatments, on the basis of whole-body doses, or two "low-doses," on the basis of average brain weight. MTX alone at lower doses and XRT alone each prolonged survival moderately. High-dose MTX was highly toxic, but low-dose MTX was well tolerated. Combined MTX and XRT caused a significant prolongation of survival in all animals that survived treatment long enough to die from tumor growth. PMID- 8008165 TI - Coexpression of interleukin-1 beta and interleukin-6 in human brain tumors. AB - Deregulation of the expression of cytokine genes appears to play a role in the development of gliomas. Interleukin-1 beta has been shown to be synthesized in small amounts by astrocytes and can induce the expression of interleukin-6. Interleukin-6 is not expressed by unstimulated astrocytes, but the deregulation of its expression has been implicated in the progression of several tumor types. In this study, tumor specimens from 16 brain tumors and 22 glioma cell lines were studied for the gene expression of both interleukin-1 beta and interleukin-6, and the coexpression of these two cytokines was found in a significant number of these specimens. The expression of these two growth factor genes may play an important role in the growth and development of human gliomas. PMID- 8008166 TI - Prognostic significance of Ki-67 proliferation index in supratentorial fibrillary astrocytic neoplasms. AB - Histological grading of fibrillary astrocytic neoplasms has proved to be a valuable prognostic tool, but potentially could benefit from more objective data, such as estimates of proliferative rate. The authors have investigated the prognostic utility of quantitative Ki-67 immunoreactivity in a prospective survival analysis of 36 adult patients with astrocytoma, anaplastic astrocytoma, or glioblastoma multiforme diagnosed between 1987 and 1992. A digital image analyzer was used to assay proliferation indices (PIs) in surgical biopsy specimens obtained at first diagnosis (32 of 36) or at a second biopsy of histologically unchanged high-grade disease (4 of 36). A Ki-67 PI of > or = 7.5% was associated with higher histological grade and poorer survival, and the Ki-67 PI was more significantly related to survival (P < 0.001) than histological grade as determined by a modified Ringertz grading system (P = 0.002). Survival analysis within histological grades suggested that astrocytoma patients with PI > or = 3% may be at increased risk for shorter survival than those with PI < 3%. PMID- 8008167 TI - Prognostic significance of flow cytometry deoxyribonucleic acid analysis of human oligodendrogliomas. AB - Flow cytometry was used to determine the deoxyribonucleic acid ploidy and proliferative activity of 60 oligodendrogliomas and oligoastrocytomas. The relationships among survival, ploidy, proliferation, histological features, and clinical variables were analyzed. Survival was strongly associated with the S phase fraction (P < 0.001). Three groups with significantly different survival rates were defined, based on S-phase fraction ranges of < 3%, 3 to 5.9%, and > 6%. Significant associations between survival and age at diagnosis (P < 0.001), tumor grade (P < 0.001), and extent of surgery (P < 0.01) were found also. The poor correlation between mitotic figures and survival in oligodendrogliomas that has been reported previously emphasizes the need for an accurate method to measure proliferative activity. Our study demonstrated the usefulness of the flow cytometry-determined S-phase fraction in this regard and demonstrated that specific reference ranges could be defined for clinical application. In contrast, the determination of ploidy by flow cytometry was not useful in the evaluation of oligodendrogliomas. PMID- 8008168 TI - Preservation of hearing in operations on acoustic tumors: an alternative to recording brain stem auditory evoked potentials. AB - The monitoring of auditory function by recording brain stem auditory evoked potentials in patients undergoing removal of acoustic tumors is hampered by the small amplitude of the brain stem auditory evoked potentials. Because several thousands of responses must be added, it takes several minutes to obtain an interpretable record. Recordings done directly from the exposed eighth nerve have much higher amplitudes, and, therefore, interpretable responses can be obtained after only a few responses have been added. However, it is difficult to place the recording electrode in an optimal position and the electrode may interfere with the removal of the tumor. In this report, we show that evoked potentials from the cochlear nucleus, which can be recorded by placing an electrode in the lateral recess of the fourth ventricle, have a large amplitude, and that the electrode placed in this way does not interfere with the removal of the tumor. This way of monitoring, therefore, yields interpretable responses within 15 to 20 seconds, or less, and makes it possible to detect injuries to the entire intracranial portion of the eighth nerve, just as brain stem auditory evoked potentials do, but 20 to 50 times faster. PMID- 8008169 TI - Cellulose acetate polymer thrombosis for the emergency treatment of aneurysms: angiographic findings, clinical experience, and histopathological study. AB - Cellulose acetate polymer solution is a liquid thrombotic material that hardens into the shape of an aneurysm into which it is injected. Therapy using this solution is a rapid technique that helps prevent the rupture of aneurysms, especially those that extravasate contrast material during angiography in the acute stage of subarachnoid hemorrhage. Using this polymer solution and an endovascular technique, we treated two patients who had aneurysms of the basilar and anterior communicating arteries with extravasation of contrast material during angiography a few hours after the initial subarachnoid hemorrhage. In one patient with an aneurysm of the anterior communicating artery, the aneurysm's wall was perforated with the catheter during neurointerventional procedures. In both patients, postoperative angiograms demonstrated obliteration of the aneurysmal dome, including the site of extravasation or perforation. The parent artery and surrounding perforating branches were preserved. Although we do not advocate aggressive therapy for patients who bleed during angiography, we pursued this therapy in these two patients because of the opportunity to introduce cellulose acetate polymer in an attempt to preserve the patients' lives. Unfortunately, both patients died. Histopathological studies performed at the time of autopsy demonstrated that the luminal surface of cellulose acetate polymer was covered with thrombus by 6 days after cellulose acetate polymer thrombosis. By 10 days, the thrombus had a prominent fibrin network, a concentrated plasma component, and few fibrocytes adhering to its luminal surface.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8008170 TI - Intraoperative motor and sensory monitoring of the cauda equina. AB - A set of standard techniques to monitor the motor and sensory function of the cauda equina is proposed for surgery in the lumbosacral spinal canal for the release of a tethered cord or the removal of a neoplasm. Continuous loudspeaker controlled recording of electromyographic activity in four leg muscles of both sides supplied the surgeon with immediate feedback on injury to any of the motor roots from the second lumbar to the fourth sacral segment. Continuous recording of tibial nerve somatosensory evoked potentials yielded information about the functional state of parts of the lumbosacral sensory pathways. Motor roots could be identified by electrical stimulation in the operating field with bipolar stimulation forceps and recording of compound muscle action potentials from the leg muscles. Sensory nerve roots could be identified by nerve root somatosensory evoked potentials recorded from the scalp after the electrical stimulation of the exposed nerve. This set-up is a combination of previously developed monitoring techniques and provides the surgeon with functional information: 1) continuous feedback on the state of the endangered motor and sensory function of the cauda equina; and 2) rapid anatomical identification of nerve roots and their distinction from fibrous or neoplastic structures. PMID- 8008171 TI - Genetic aberrations in human brain tumors. AB - Over the last decade, much has been learned about the genetic changes that occur in human neoplasia and how they contribute to the neoplastic state. Oncogenes and tumor suppressor genes have been identified, and many powerful molecular genetic techniques have emerged. Brain tumors have been intensively studied as part of this process. Specific and recurring genetic alterations have been identified and are associated with specific tumor types. In astrocytomas, for example, losses of genetic material on chromosomes 10 and 17 and amplification of the epidermal growth factor receptor gene seem important in pathogenesis, with the loss of chromosome 10 and the amplification of epidermal growth factor receptor being strongly associated with glioblastoma multiforme. Meningiomas, on the other hand, have usually lost part or all of chromosome 22. Brain tumors also express growth factors and growth factor receptors that may be important in promoting tumor growth and angiogenesis. These include epidermal growth factor, transforming growth factor-alpha, platelet-derived growth factor, the fibroblast growth factors, and vascular endothelial growth factor. In this article, we review the genetic aberrations that occur in the major types of brain tumors, including glial tumors, meningiomas, acoustic neuromas, medulloblastomas, primitive neuroectodermal tumors, and pituitary tumors. Wherever possible, clinical correlations have been made concerning the prognostic and therapeutic implications of specific aberrations. We also provide some background about the cytogenetic and molecular genetic techniques that have contributed to the description and understanding of these alterations and speculate as to some clinical and basic science issues that might be explored in the future. PMID- 8008172 TI - Sphenoid wing meningioma progression after placement of a subcutaneous progesterone agonist contraceptive implant. AB - A causal relationship between sex steroids and meningioma proliferation has long been suspected. We report a case of the clinical progression of a sphenoid wing meningioma after the placement of Norplant, a subcutaneous contraceptive implant containing levonorgestrel, a progesterone agonist. Although not proof of causation, this observation lends further credence to the importance of progesterone receptors in the growth and possible treatment of meningiomas. PMID- 8008174 TI - Neurological recovery after cranioplasty. AB - A patient who sustained a gunshot wound to the head was successfully treated with acute neurosurgical intervention. Six months after the injury, cranioplasty was used to repair a large skull defect. After cranioplasty, the patient developed significant improvement in motor function in his left upper extremity, which had been plegic after his injury. Although the mechanism of neurological recovery after cranioplasty is controversial, the occurrence of such improvement may be a sufficient indication for cranioplasty in certain patients. PMID- 8008173 TI - Multilobulated cystic formation in the brain stem with Benedikt's syndrome: case report. AB - A 26-year-old man presented with an unusual multilobulated cystic formation in the brain stem with normal pressure hydrocephalus, followed by fluctuating cyst volume and Benedikt's syndrome. Ventriculoperitoneal shunting to relieve the hydrocephalus caused an increased cystic size, resulting in worsened neurological deficits. Cystectomy and an additional shunt resolved the symptoms. Immunohistochemical and electron microscopic examinations of the surgical specimen revealed no epithelial lining but numerous astrocytic processes on the luminal surface, probably resulting from expansion of the cyst. This case suggests that cystectomy before shunt emplacement is recommended in similar cases. PMID- 8008175 TI - Familial occurrence of polymorphous oligodendroglioma. AB - A case of familial polymorphous oligodendroglioma, occurring in a brother and sister, is presented. Polymorphous oligodendrogliomas have a characteristic histopathology consisting of scattered multinucleated giant cells against a typical oligodendroglial background. The oligodendroglial character of the tumors was underlined by positive immunostaining for antigalactocerebroside, anticarbonic anhydrase, and anti-leu-7, without expression of glial fibrillary acidic protein. Both tumors were immunopositive for p53, suggesting a mutation in the p53 gene. No incidence of cancer was recorded in the family. This is the first report of familial occurrence of this particular subtype of oligodendroglioma. PMID- 8008176 TI - Creutzfeldt-Jakob disease in a pregnant woman with an implanted dura mater graft. AB - A 28-year-old woman with prior neurosurgery involving the placement of a cadaveric dural graft developed a rapidly progressive neurodegenerative disorder with prominent cerebellar dysfunction that was proven at autopsy to be Creutzfeldt-Jakob disease. She represents the second American to develop Creutzfeldt-Jakob disease in association with a dural graft. The unusual features of the case include the patient's initial clinical presentation with cerebellar ataxia in the absence of dementia, the widespread presence of kuru-type amyloid plaques on a histological examination of the brain, the development of clinical symptoms during pregnancy, and the subsequent delivery of a child who remains healthy at the age of 3 years. PMID- 8008177 TI - Creutzfeldt-Jakob disease transmitted by a cadaveric dura mater graft. AB - We report a case of Creutzfeldt-Jakob disease developing in a 31-year-old woman 56 months after she received a cadaveric dura mater graft after the removal of a giant pituitary adenoma. Creutzfeldt-Jakob disease was confirmed by a brain autopsy and the existence of an abnormal isoform of prion protein, verified by both immunohistochemical and Western blot analysis. Moreover, prion protein gene analysis was shown in this case to possess a wild-type genotype. The characteristics of Creutzfeldt-Jakob disease after a cadaveric dura mater graft are reviewed and discussed. PMID- 8008178 TI - Aneurysmography for visualizing large aneurysms. AB - We report a case of a large cavernous sinus aneurysm, in which conventional angiography did not clearly demonstrate the exact form and the position of the neck. Superselective angiography performed with the catheter tip in the lumen of the aneurysm and with the internal carotid artery occluded just proximal to its neck is a new technique that demonstrates the morphological details of an entire aneurysm. With the use of cineangiography, the exact volume of the aneurysm was defined. The valuable aneurysmographic information obtained was useful in achieving occlusion of the aneurysm, while preserving the parent artery. PMID- 8008179 TI - A transcondylar approach to the arteriovenous malformation at the ventral cervicomedullary junction: report of three cases. AB - Arteriovenous malformation at the cerevicomedullary junction is a rare disorder, usually presenting with subarachnoid hemorrhage. The diagnosis is difficult because of its anatomical location. In addition, the ventral location of these arteriovenous malformations makes surgical treatment difficult. We describe three cases surgically treated with a transcondylar approach. The usefulness of digital subtraction angiography and magnetic resonance imaging is discussed. The technique of the transcondylar approach is also described, including C1 hemilaminectomy, unroofing of the transverse foramen of C1 to obtain control of the vertebral artery, and partial resection of the occipital condyle and lateral atlantal mass by extradural drilling. This approach provides direct access to the ventral portion of the cervicomedullary junction. PMID- 8008181 TI - Consensus conference on the neurosurgical management of pain. AB - On the recommendation of the American Association of Neurological Surgeons Section on Pain, a satellite conference was organized for the 1993 annual meeting to work toward a consensus regarding the indications, expected outcomes, and potential complications of neurosurgical procedures for intractable pain. Twenty two experts in the field attended this 2-day conference to consolidate our understanding of the role of neurosurgical procedures in pain management and to review critically the methodologies for clinical studies. With the support of the Section on Pain, this consensus development process will continue in order to refine the application and study of neurosurgical procedures for pain. PMID- 8008180 TI - Ranging accuracy test of the sonic microstereometric system. AB - We have recently introduced a new type of ultrasonic-based, three-dimensional ranging system for the localization of small handheld surgical tools to be used during operation in open stereotactic brain surgery. This targeting system has now been extensively laboratory tested during thousands of measuring cycles with a CNC-based measuring table. The typical accuracy found in a single direction was 0.4 mm and better. The accuracy vector in space was 0.897 mm (n = 2312). The test retest accuracy was typically 0.4 mm. With the given accuracy, the system is suitable for all ranging tasks in open stereotactically guided microsurgery. PMID- 8008182 TI - Death in the Sick Chamber by Edvard Munch. PMID- 8008183 TI - False aneurysm associated with rupture of an arteriovenous malformation- implication for treatment: case report. PMID- 8008184 TI - Neuro-ophthalmic complications of intracranial catheters. PMID- 8008185 TI - Hair and neurosurgery. PMID- 8008186 TI - Accidental head trauma and retinal hemorrhage. PMID- 8008187 TI - Investigations of the bacteriological factors in clean neurosurgical cases. PMID- 8008188 TI - Delivery of virus-sized iron oxide particles to rodent CNS neurons. AB - Delivery of viral particles to the brain is limited by the volume of distribution that can be obtained. Additionally, there is currently no way to non-invasively monitor the distribution of virus following delivery to the central nervous system (CNS). To examine the delivery of virus-sized particles across the blood brain barrier (BBB), dextran coated, superparamagnetic monocrystalline iron oxide particles, with a hydrodynamic diameter of 20 +/- 4 nm, were delivered to rat brain by direct intracerebral inoculation or by osmotic BBB disruption with hypertonic mannitol. Delivery of these particles was documented by magnetic resonance (MR) imaging and, unexpectedly, neuronal uptake was demonstrated by histochemical staining. Electron microscopy (EM) confirmed iron particle delivery across the capillary basement membrane and localization within CNS parenchymal cells following administration with BBB disruption. This is the first histologic and ultrastructural documentation of the delivery of particles the size of virions across the blood-brain barrier. Additionally, these dextran-coated, iron oxide particles may be useful, in and of themselves, as vectors for diagnostic and/or therapeutic interventions directed at the CNS. PMID- 8008189 TI - Value-dependent selection in the brain: simulation in a synthetic neural model. AB - Many forms of learning depend on the ability of an organism to sense and react to the adaptive value of its behavior. Such value, if reflected in the activity of specific neural structures (neural value systems), can selectively increase the probability of adaptive behaviors by modulating synaptic changes in the circuits relevant to those behaviors. Neuromodulatory systems in the brain are well suited to carry out this process since they respond to evolutionarily important cues (innate value), broadcast their responses to widely distributed areas of the brain through diffuse projections, and release substances that can modulate changes in synaptic strength. The main aim of this paper is to show that, if value-dependent modulation is extended to the inputs of neural value systems themselves, initially neutral cues can acquire value. This process has important implications for the acquisition of behavioral sequences. We have used a synthetic neural model to illustrate value-dependent acquisition of a simple foveation response to a visual stimulus. We then examine the improvement that ensues when the connections to the value system are themselves plastic and thus become able to mediate acquired value. Using a second-order conditioning paradigm, we demonstrate that auditory discrimination can occur in the model in the absence of direct positive reinforcement and even in the presence of slight negative reinforcement. The discriminative responses are accompanied by value dependent plasticity of receptive fields, as reflected in the selective augmentation of unit responses to valuable sensory cues. We then consider the time-course during learning of the responses of the value system and the transfer of these responses from one sensory modality to another. Finally, we discuss the relation of value-dependent learning to models of reinforcement learning. The results obtained from these simulations can be directly related to various reported experimental findings and provide additional support for the application of selectional principles to the analysis of brain and behavior. PMID- 8008190 TI - Synchronization of area CA3 hippocampal pyramidal cells and non-granule cells of the dentate gyrus in bicuculline-treated rat hippocampal slices. AB - A recent study has described synchronous burst discharges of dentate hilar neurons and area CA3 pyramidal cells in the presence of the convulsants 4 aminopyridine and picrotoxin in guinea-pig hippocampal slices [Muller W. and Misgeld U. (1991) J. Neurophysiol. 65, 141-147]. To examine the synchronous activity of dentate cells and area CA3 pyramidal cells further, epileptiform burst discharges were examined in morphologically and/or electrophysiologically identified non-granule cells in the hilus and granule cell layer of the rat dentate gyrus and compared to simultaneously-recorded pyramidal cells of area CA3a, b, and c. Specifically, the types of dentate cells and the types of discharge were examined, as well as the timing of burst discharge of dentate cells relative to different cells of area CA3. In the presence of the GABAA receptor antagonist bicuculline (30 microM), all dentate cell types discharged in rhythmic, spontaneous bursts that were synchronized with area CA3 pyramidal cell epileptiform bursts. The sampled cells included hilar "mossy" cells, hilar fast spiking cells (putative interneurons) as well as interneurons located in the granule cell layer, such as the pyramidal "basket" cells. Simultaneous recording from dentate non-granule cells and area CA3 pyramidal cells during exposure to bicuculline demonstrated that stimulus-evoked and spontaneous epileptiform bursts occurred almost exactly at the same time; there were only a few milliseconds between the onsets of pyramidal cell bursts and dentate cell bursts, with the pyramidal cell preceding the dentate cell in almost every case. There were no systematic differences among dentate cell types in the extent they lagged behind pyramidal cells, and there were no detectable differences among area CA3 pyramidal cells. In slices that were cut between area CA3 and the dentate gyrus, epileptiform bursts occurred in area CA3 but not in the dentate. These findings suggest that, in the absence of GABAA receptor-mediated inhibition, excitatory pathways from area CA3 to the dentate gyrus are strong and widespread. These pathways, and possibly other mechanisms, can lead to tightly synchronized action potential discharge of pyramidal cells and dentate non-granule cells. The results also suggest that disinhibition alone is insufficient to cause synchronous bursts in the dentate gyrus, in contrast to area CA3. PMID- 8008191 TI - Effects of adrenal medulla grafts on memory capacities of rats after hippocampal lesions. AB - Behavioral and immunocytochemical techniques were used to study the effects of adrenal medulla grafts implanted in hippocampus--after lesion of this structure- on the memory capacities of rats. Performances of the grafted rats in the radial maze test were significantly improved and, in some aspects, fully restored. On the other hand, grafts had no significant effects on a one-trial spatial recognition test and impaired object recognition. Immunocytochemical identification showed that the grafts contained chromaffin cells with a choline acetyltransferase stainings while, in parallel, phenylethanolamine-N methyltransferase stainings seemed to be decreased. Cholinergic innervation was established between the graft and the host hippocampus. A likely interpretation of this complex pattern of results is that the functional effects of the grafts depended on the arousal level induced by the behavioral task. At the neurobiological level, these effects probably set into play an interaction between opioid, catecholaminergic and cholinergic factors. Our results may contribute to the clarification of the problem of specificity of functional effects of intracerebral grafts as well as the problem of hippocampal role in learning and memory. PMID- 8008192 TI - The action of a phorbol ester on voltage-dependent parameters of the sodium current in isolated hippocampal neurons. AB - The action of a phorbol ester (phorbol-12,13-diacetate) on the voltage-activated sodium current has been investigated by the voltage-clamp method in acutely isolated pyramidal neurons from rat hippocampus. The intracellular perfusion of isolated pyramidal neurons for 30-40 min induced a gradual 10-15 mV shift in both the current-voltage relationship and voltage-dependent steady-state inactivation to more negative potentials. The application of phorbol ester (1-10 microM) to isolated neurons for the same time increased the amplitude of sodium current by 15-20%, shifted the above-mentioned voltage-dependent parameters for an additional 10-15 mV in the same direction and changed the slope of the steady state inactivation curve. In contrast, after prolonged incubation of slices in the phorbol ester-containing solution (1-10 microM) for 0.5-3 h, subsequent application of phorbol ester at the same concentration caused neither the addition shift of the voltage-dependent characteristics of sodium channels nor the change of the slope of the steady-state inactivation curve. However, in this case an increase in the amplitude of sodium current by 15-20% during 30-40 min intracellular perfusion was observed.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8008193 TI - Inositol 1,3,4,5-tetrakisphosphate as a mediator of neuronal death in ischemic hippocampus. AB - Selective death of CA1 pyramidal neurons after transient forebrain ischemia has attracted interest for its possible relation to the pathogenesis of memory deficits and dementia. Using whole cell patch-clamp recording from CA1 pyramidal neurons in hippocampal slices of gerbils after ischemia we studied the intracellular signaling mechanisms related to the phosphoinositide cycle. Intracellular application of an antibody against phosphatidylinositol 4,5 bisphosphate rescued ischemic neurons from stimulus-induced irreversible depolarization. Furthermore, application of inositol 1,3,4,5-tetrakisphosphate in normal cells caused an irreversible depolarization in response to synaptic input, which mimicked the deterioration of ischemic neurons. Depolarization of both ischemic and normal neurons in the presence of inositol 1,3,4,5-tetrakisphosphate was prevented by the addition of the Ca2+ chelator, 1,2-bis(o-aminophenoxy)ethane N,N,N',N'-tetra-acetate. Application of antibody against inositol 1,4,5 triphosphate 3-kinase, which blocks formation of inositol 1,3,4,5 tetrakisphosphate, also protected against cell deterioration. Our results suggest that the vulnerability of hippocampal pyramidal neurons following ischemia is caused by a disturbed phosphoinositide cascade, with one metabolite, inositol 1,3,4,5-tetrakisphosphate, playing a key role in the induction of Ca2+ accumulation, which leads to neuronal death. PMID- 8008194 TI - Sulphur-containing excitatory amino acid-stimulated inositol phosphate formation in primary cultures of cerebellar granule cells is mediated predominantly by N methyl-D-aspartate receptors. AB - The stimulatory effect of excitatory sulphur-containing amino acids on inositol phosphate formation was investigated in primary cultures of cerebellar granule cells. L-Cysteine sulphinate (CSA), L-cysteate (CA), L-homocysteine sulphinate (HCSA), L-homocysteate (HCA) and S-sulpho-L-cysteine (SSC) dose-dependently stimulated the formation of [3H]inositol phosphates exhibiting EC50 values in the range 60-200 microM and maximal effects of six- to 17-fold that of basal [3H]inositol phosphate levels. Endogenous L-glutamate spontaneously released into the extracellular medium or following exposure of cells to HCSA, HCA or SSC did not contribute significantly to formation of [3H]inositol phosphates, whereas 10% of the total [3H]inositol phosphates accumulated following exposure to CSA and CA was due to released L-glutamate. The selective N-methyl-D-aspartate receptor antagonist, D,L-2-amino-5-phosphonopentanoic acid (APV, 500 microM) attenuated by 20% (HCSA) to between 80 and 100% (CSA, CA, SSC, HCA) the formation of [3H]inositol phosphates induced by 1 mM sulphur-containing amino acids. When, however, HCSA was used at 100 microM (a concentration near to its EC50 for phosphoinositide hydrolysis), APV inhibited induced responses by 70%. Sulphur containing amino acid-stimulated [3H]inositol phosphate formation was unaffected by the alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX, 10 microM). Inhibition of sulphur-containing amino acid-stimulated [3H]inositol phosphate formation by co administration of APV and CNQX was similar to that obtained in the presence of APV alone. CSA-, CA-, SSC- and HCA-stimulated [3H]inositol phosphate formation was markedly reduced by removal of Ca2+ from the extracellular medium whereas that stimulated by HCSA was less affected. A similar inhibitory profile was observed when the levels of sulphur-containing amino acid-induced increases in intracellular free calcium ([Ca2+]i) were measured in the presence of 500 microM APV; 1 mM HCSA-induced responses being inhibited by only 30% whereas responses to the remaining sulphur-containing amino acid (also at 1 mM) were inhibited by > 45%. When the sulphur-containing amino acids were used at concentrations approximating their EC50 values for phosphoinositide hydrolysis, APV inhibited the induced increases in [Ca2+]i by 70-100%. HCA and SSC co-administered with the less efficacious but selective metabotropic glutamate receptor agonist, (+-)-1 aminocyclopentane-trans-1,3-dicarboxylic acid (trans-ACPD) at maximally effective concentrations (1 mM) of each agonist stimulated [3H]inositol phosphate formation in an additive manner.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8008195 TI - Serotonergic and cholinergic inhibition of mesopontine cholinergic neurons controlling REM sleep: an in vitro electrophysiological study. AB - Intracellular recordings were obtained from neurons of the laterodorsal tegmental and pedunculopontine tegmental nuclei in a brain-slice preparation. The action of exogenously applied 5-hydroxytryptamine and acetylcholine was studied on NADPH diaphorase-labeled cells which contain nitric oxide synthase and are presumed to be cholinergic. Our results indicated that these cells were hyperpolarized by both 5-hydroxytryptamine and acetylcholine; the ionic mechanism of this inhibition was investigated using current and voltage clamp methods. Cells voltage-clamped at resting membrane potential exhibited a net outward current and an increased membrane conductance during 5-hydroxytryptamine and acetylcholine mediated inhibition. The membrane hyperpolarization and outward current generated by this paradigm reversed near the expected K equilibrium potential and was blocked by low concentrations of extracellular Ba. The 5-hydroxytryptamine- and acetylcholine-dependent currents showed inward rectification and the reversal potential shifted in the depolarizing direction by about 15 mV for a doubling of extracellular K, indicating that both 5-hydroxytryptamine and acetylcholine activate inwardly rectifying, potassium-selective conductances. The 5 hydroxytryptamine-evoked hyperpolarization was antagonized by spiperone and mimicked by (+)8-hydroxy-2-(Di-N-propylamino)-tetralin suggesting the presence of a 5-hydroxytryptamine1A receptor while the acetylcholine-evoked hyperpolarization was blocked by atropine and only high concentrations of pirenzepine, suggesting a muscarinic M2 receptor. The outward currents evoked by 5-hydroxytryptamine and acetylcholine were not additive, suggesting that both receptors are coupled to an overlapping pool of K channels as has been observed in several systems in which receptors are coupled to effectors by G-proteins. These results indicate that the dominant actions of 5-hydroxytryptamine and acetylcholine relate to the inhibition of mesopontine cholinergic neurons via activation of an overlapping pool of inwardly rectifying K channels. Cholinergic neurons of these nuclei are thought to play an instrumental role in the induction and maintenance of rapid eye movement sleep. It has been previously hypothesized that acetylcholine would be excitatory and that 5-hydroxytryptamine would be inhibitory to these cells in the context of rapid eye movement sleep. [McCarley R. and Massaquoi S. (1986) Am. J. Physiol. 251, R1011-R1029; McCarley R. W. et al. (1975) Science 189, 58-60]. Our results are consistent with the proposed inhibitory action of 5 hydroxytryptamine but indicate recurrent input to cholinergic neurons would be inhibitory. Accordingly, models of the neural substrate underlying rapid eye movement sleep production need to be changed to reflect this inhibitory action of acetylcholine on cholinergic neurons. PMID- 8008196 TI - A comparison of the muscarinic response and morphological properties of identified cells in the guinea-pig olfactory cortex in vitro. AB - The electrophysiological and morphological characteristics of neurons in the guinea-pig olfactory cortex brain slice were investigated using a combined intracellular recording and neurobiotin-dye filling technique, in an attempt to show whether a clear relation existed between cell morphology and excitatory muscarinic response profile. Out of 46 sampled neurons, 25 (termed type 1), responded to bath-application of the muscarinic agonist oxotremorine-M (10 microM, 2-3 min) with a strong and persistent excitation coupled with the appearance of a slow depolarizing afterpotential (10-20 mV amplitude) following a large depolarizing stimulus. These neurons were identified as deep pyramidal cells located in cortical layer III, with characteristic pyramidal/ovoid shaped cell bodies, prominent apical dendrites with branches extending to the surface, and extensive basal dendritic trees. The cells showed a regular spiking pattern in response to injected depolarizing current, with no evidence of bursting behaviour. Nine cells (termed type 2), were strongly excited by oxotremorine-M, but only generated a weak depolarizing afterpotential (< 5 mV) following stimulation. These neurons (located in layer III or at layer II-III border) had a variable, non-pyramidal morphology with either a fusiform/tripolar, stellate/multipolar or bipolar/bi-tufted appearance, respectively. Apart from a more prominent post-spike afterhyperpolarization observed in some type 2 cells, their resting membrane properties and firing patterns were indistinguishable from those of type 1 responding cells. Twelve cells (termed type 3) showed little or no excitatory response to oxotremorine-M, and never generated a post-stimulus slow afterdepolarization. These cells (within compact layer II) had the morphological features of superficial pyramidal cells, typified by their short apical trunks and well-developed apical dendritic trees. They could be distinguished electrophysiologically by their ability to show spike fractionation during injection of large depolarizing current pulses. The morphology and laminar position of neurobiotin-filled cells was also compared with those of cells stained by the Golgi-Cox method. Some factors that may have contributed to the observed differences in muscarinic response profile are discussed. It is proposed that the selective muscarinic induction of the slow depolarizing afterpotential phenomenon in deep pyramidal cells may be important in olfactory cortical learning and memory processes. PMID- 8008197 TI - Muscarinic inhibition of two potassium currents in guinea-pig prevertebral neurons: differentiation by extracellular cesium. AB - Muscarinic responses were studied in dissociated guinea-pig celiac ganglion neurons using the whole-cell voltage-clamp technique. Muscarine (0.025-1 mM; EC50 = 95 microM) administered to cells for 1.5 s evoked inward shifts in holding current in 53 of 74 cells. The amplitude of the inward current transients decreased with hyperpolarization and the null potential averaged -71 +/- 3.4 mV (n = 11). The currents that underlie the responses to muscarine were examined with hyperpolarizing voltage stepping protocols to -100 mV from a holding potential of -30 mV. Eighty-one per cent of cells displayed voltage-dependent current relaxations characteristic of the M-potassium current. Twenty per cent of responding cells displayed no M-current but only a voltage-independent current consistent with a leak current. In the latter type of cells, the muscarine-evoked inward currents reversed near EK and became outward at more hyperpolarized potentials. Analysis of steady state I-V relationships before and after bath application of muscarine showed that the two muscarine-sensitive potassium currents were distributed differently among three types of cells: (i) with M current (18%); (ii) with leak current (18%); and (iii) with M-current and with leak current (64%). Cesium and barium were used to differentiate the M-current and the muscarine-sensitive leak current. Barium (2 mM) reduced the M-current and the leak potassium current, whereas cesium (2 mM) reduced the M-current but did not affect leak current. Thus, barium reduced the amplitude of muscarinic responses by 79% but cesium reduced them by only 14%. We conclude that muscarinic responses in guinea-pig celiac neurons are produced by suppression of two K+ currents: the M-current and a muscarine-sensitive leak current. These two currents are differentially susceptible to the potassium channel blockers barium and cesium. PMID- 8008198 TI - Excitatory amino acid receptor antagonists modify regional cerebral metabolic responses to levodopa in 6-hydroxydopamine-lesioned rats. AB - Excitatory amino acid receptor antagonists have been proposed as novel therapeutic agents to be used with levopoda in the treatment of Parkinson's disease. We examined the neural substrates for the interaction between levodopa and antagonists of either the alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid or N-methyl-D-aspartate type of excitatory amino acid receptor using 2 deoxyglucose autoradiography. Thus, we compared the effects of the alpha-amino-3 hydroxy-5-methylisoxazole-4-propionic acid receptor antagonist 2,3-dihydroxy-6 nitro-7-sulfamoyl-benzo(F)quinoxaline (10 mg/kg, i.v.) and the N-methyl-D aspartate antagonist MK-801 (0.1 mg/kg, i.v.) on cerebral metabolic responses to levodopa (25 mg/kg, i.v., with 12.5 mg/kg benserazide) in rats with a unilateral nigrostriatal pathway lesion. Levodopa increased glucose utilization ipsilateral to the lesion in substantia nigra pars reticula (up to 104%), entopeduncular nucleus (up 90%) and subthalamic nucleus (up 30%), indicating that levodopa alters striatal output through the striatonigral, striatoentopeduncular and striatopallidal pathways. Levodopa also decreased metabolic rate in lateral habenula (down 39%), a target of projections from entopeduncular nucleus, implying a reduction in basal ganglia output. 2,3-Dihydroxy-6-nitro-7-sulfamoyl benzo(F)quinoxaline and MK-801 by themselves did not affect glucose utilization in any of these regions. Pretreatment with 2,3-dihydroxy-6-nitro-7-sulfamoyl benzo(F)quinoxaline reduced the effect of levodopa in substantia nigra pars reticulata but not in entopeduncular nucleus or subthalamic nucleus, while MK-801 attenuated the effect of levodopa in all three of these structures; neither 2,3 dihydroxy-6-nitro-7-sulfamoyl-benzo(F)quinoxaline nor MK-801 altered the effect of levodopa in lateral habenula. When given at the same doses to a separate group of lesioned animals, neither 2,3-dihydroxy-6-nitro-7-sulfamoyl benzo(F)quinoxaline nor MK-801 affected rotational behavior elicited by levodopa. These findings indicate that alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid and N-methyl-D-aspartate receptor antagonists differentially modify dopamine receptor-mediated striatal output. alpha-Amino-3-hydroxy-5-methylisoxazole-4 propionic acid receptor blockade may preferentially attenuate the effect of dopamine receptor activation on the striatonigral pathway, while N-methyl-D aspartate blockade appears to reduce the actions of dopamine on the striatonigral, striatoentopeduncular and striatopallidal pathways.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8008199 TI - Heterogeneity of evoked dopamine overflow within the striatal and striatoamygdaloid regions. AB - The heterogeneity of evoked dopamine overflow in vivo was examined and compared in striatal and striatoamygdaloid regions of the rat. The characteristics of appearance and disappearance rates and the maximum concentration elicited were determined from overflow curves measured by fast-scan cyclic voltammetry. Overall, the characteristics of evoked dopamine overflow were quite variable in the striatum compared to the relative uniformity of overflow in the basolateral amygdaloid nucleus. In addition, there was a significant decrease in the extracellular disappearance rate of evoked dopamine with depth in the striatum. This gradient did not alter with passage from the caudate-putamen to the nucleus accumbens and no change was observed for the appearance rate or maximum concentration. In contrast, differences in evoked dopamine overflow within the striatoamygdaloid region were sharply defined dorsoventrally and appeared to be region-specific. Dopamine terminal fields in the striatum are not clearly demarcated into the caudate-putamen and nucleus accumbens, but may exist as a continuum. The uptake of dopamine appears to be the distinguishing characteristic for the regulation of extracellular dopamine levels in the striatum and the basolateral amygdaloid nucleus. PMID- 8008200 TI - Intense cold noxious stimulation of the rat hindpaw induces c-fos expression in lumbar spinal cord neurons. AB - This study evaluated Fos-like immunoreactivity in lumbar spinal cord neurons following intense cold stimulation and then the modifications induced by opioid administration. Under urethane anaesthesia, the rat's right foot was stimulated by holding it in a regulated temperature bath at 15, 10, 0, -10, -15, -17.5 or 20 degrees C. There was no or little Fos-like immunoreactivity in lumbar spinal cord neurons when the paw was at temperatures between 15 and -10 degrees C (0-5 Fos-like immunoreactive neurons/section). The threshold to induce consistent c fos expression was -15 degrees C. From -15 to -20 degrees C, the number of Fos like immunoreactive neurons increased with decreases in temperature. At -20 degrees C, Fos-like immunoreactive neurons were numerous in L3 and L4 segments, in laminae I-II (approximately 60 Fos-like immunoreactive neurons/section) and to a lesser extent in laminae V-VI (approximately 20). Almost no Fos-like immunoreactivity was present in laminae III-IV (< 5). At -20 degrees C, the number of Fos-like immunoreactive neurons increased with the duration of the stimulation. The number of Fos-like immunoreactive neurons induced by the cold stimulation temperatures was significantly decreased by pretreatment with 10 mg/kg s.c. morphine and moderately decreased by 5 mg/kg s.c. This effect was antagonized by the combined administration of morphine (10 mg/kg s.c.) and naloxone (2 mg/kg s.c.). Naloxone (2 mg/kg s.c.) significantly increased the number of Fos-like immunoreactive neurons induced by -20 degrees C as compared to saline-injected rats. This study showed that Fos-like immunoreactivity distribution is in good agreement with the location of neurons receiving noxious inputs and that the threshold to induce c-fos expression with cold was unexpectedly low at -15 degrees C. Taking into account, on the one hand, previous investigations using the same technique using noxious heat stimulation and, on the other hand, electrophysiological and psychophysiological studies using cold stimulation in animals and humans, our results suggest that Fos-like immunoreactivity induced by extremely cold stimulation, which seems to reproduce frostbite, may reflect activation of nociceptors due to vasoconstriction. PMID- 8008201 TI - Ultrastructural co-localization of neuropeptide Y and vasoactive intestinal polypeptide in neurosecretory vesicles of submucous neurons in the rat jejunum. AB - The localization of vasoactive intestinal polypeptide and neuropeptide Y in submucous nerves of rat jejunum was studied using both single-label pre-embedding immunocytochemistry and post-embedding double-label immunogold techniques. Vasoactive intestinal polypeptide-immunoreactive fibres and cell bodies were regularly observed in submucous plexus and a similar distribution was seen for neuropeptide Y. Varicose fibres were observed in single-label studies and when areas of specific interest were subjected to double-label immunogold protocols these immunoreactive profiles exhibited vesicles clearly stained for both vasoactive intestinal polypeptide and neuropeptide Y. Synaptic vesicles in immunopositive fibres observed close to the mucosa (and elsewhere in the submucosa) were dense-cored with an average diameter of 80 nm. Nerves associated with vascular elements only stained for neuropeptide Y, not for vasoactive intestinal polypeptide. These findings suggest that these two unrelated enteric peptides are co-released in the vicinity of the mucosal lining and the likely implications of such co-release are discussed. PMID- 8008202 TI - Biosynthesis of proteins of large dense-core vesicles in rat PC12 cells: regulation by forskolin and phorbol ester. AB - We have investigated the influence of various second messengers on the biosynthesis of large dense-core vesicle constituents in rat PC12 cells. After treatment with forskolin, phorbol ester or a combination of both substances for up to six days, the messenger RNA levels of several vesicle components were determined by northern blotting. Forskolin increased the expression of messenger RNA encoding the soluble proteins chromogranin B, neuropeptide Y and VGF. Addition of phorbol ester markedly enhanced the effects of forskolin. On the other hand, the expression of two further soluble proteins, chromogranin A and secretogranin II, remained fairly unchanged with all treatments tested. Amongst partly membrane-bound vesicle components, the biosynthesis of glycoprotein III and peptidylglycine alpha-amidating mono-oxygenase was significantly up-regulated by combined treatment with forskolin plus phorbol ester. The carboxypeptidase H messenger RNA increased due to phorbol ester and after long-term application of both drugs. In contrast, phorbol ester alone or plus forskolin down-regulated the expression of dopamine beta-hydroxylase. Essentially the same applies to the intrinsic membrane protein cytochrome b-561, whose messenger RNA level declined in all treatment groups. In conclusion, our results show that forskolin and phorbol ester can regulate the composition of large dense-core vesicles in quite distinct patterns. PMID- 8008203 TI - Effects of vesicular acetylcholine uptake blockers on frequency augmentation potentiation in frog neuromuscular transmission. AB - Vesamicol inhibits the vesicular loading of acetylcholine molecules. The effects of vesamicol and similarly acting compounds on neuromuscular transmission in frogs were investigated to determine whether these inhibitors-inhibit the frequency augmentation-potentiation of transmitter release. Various vesicular acetylcholine transport blockers suppressed the stimulation frequency-related release parameter, k, in a dose-dependent manner. Artane, cetiedil, chloroquine, ethodin, quinacrine, vesamicol and its benzyl-analogue, 2-(4 benzylpiperidino)cyclohexanol, had strong effects, while those of aminacrine, chlorpromazine, fluphenazine, imipramine, pyrilamine and thioridazine were weak. A significant correlation was observed between the biochemically reported values of IC50 and the electrophysiological inhibitory potencies on k at 20 microM. Contrary to expectations from the biochemical data, however, vesamicol and its benzyl-analogue showed equipotent inhibitory actions on the electrophysiological frequency augmentation-potentiation relation. Low sensitivity and low selectivity of the frequency augmentation-potentiation for vesamicol and its benzyl-analogue lead us to conclude that the vesicular acetylcholine transporter is not the site of the electrophysiological action of vesamicol and similarly acting chemicals. PMID- 8008204 TI - Suppression of long-term potentiation induction during alert wakefulness but not during 'enhanced' REM sleep after avoidance learning. AB - Major learning events are typically followed by a period during which the number and/or duration of rapid-eye movement sleep episodes is increased. Processes critical to memory formation are thought to take place during this interval of 'enhanced' rapid-eye movement sleep. We therefore compared the capacity for long term potentiation during rapid-eye movement sleep and alert wakefulness after learning. Rats were chronically implanted with electrodes for stimulation of the perforant path and recording of evoked potentials and EEG in the dentate gyrus. After obtaining baseline recordings, rats were trained on a 40-trial two-way active avoidance task. Conditioned rats exhibited a two-fold increase in the mean duration of rapid-eye movement sleep episodes, as reflected by a prolongation of the hippocampal theta rhythm. There was no change in the sleep pattern of pseudoconditioned controls, which received explicitly unpaired tones and foot shocks in a yoked design. High-frequency stimulation was applied during the second, third, and fourth major rapid-eye movement sleep episodes after active avoidance training. Another group was tetanized at matching time points during alert wakefulness. After pseudoconditioning, tetanus applied during wakefulness or rapid-eye movement sleep readily induced long-term potentiation, and there was no difference between groups in the magnitude of increase for the population excitatory postsynaptic potential slope or the population spike height as measured 1 h, 24 h, and 5 days post-tetanus.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8008205 TI - Cholinergic mechanisms in canine narcolepsy--I. Modulation of cataplexy via local drug administration into the pontine reticular formation. AB - Cataplexy in the narcoleptic canine has been shown to increase after systemic administration of cholinergic agonists. Furthermore, the number of cholinergic receptors in the pontine reticular formation of narcoleptic canines is significantly elevated. In the present study we have investigated the effects of cholinergic drugs administered directly into the pontine reticular formation on cataplexy, as defined by brief episodes of hypotonia induced by emotions, in narcoleptic canines. Carbachol and atropine were perfused through microdialysis probes implanted bilaterally in the pontine reticular formation of freely moving, narcoleptic and control Doberman pinschers. Cataplexy was quantified using the Food-Elicited Cataplexy Test, and analysed using recordings of electroencephalogram, electrooculogram and electromyogram. Cataplexy was characterized by a desynchronized electroencephalogram and a drop in electromyogram and electrooculogram activity. In narcoleptic canines, both unilateral and bilateral carbachol (10(-5) to 10(-3) M) produced a dose-dependent increase in cataplexy, which resulted in complete muscle tone suppression at the highest concentration. In control canines, neither bilateral nor unilateral carbachol (10(-5) to 10(-3) M) produced cataplexy, although bilateral carbachol, did produce muscle atonia at the highest dose (10(-3)). The increase in cataplexy after bilateral carbachol (10(-4) M) was rapidly reversed when the perfusion medium was switched to one containing atropine (10(-4) M). Bilateral atropine (10(-3) to 10(-2) M) alone did not produce any significant effects on cataplexy in narcoleptic canines; however, bilateral atropine (10(-2) M) did reduce the increase in cataplexy produced by systemic administration of physostigmine (0.05 mg/kg, i.v.). These findings demonstrate that cataplexy in narcoleptic canines can be stimulated by applying cholinergic agonists directly into the pontine reticular formation. The ability of atropine to inhibit locally and systemically stimulated cataplexy indicates that the pontine reticular formation is a critical component in cholinergic stimulation of cataplexy. Therefore, it is suggested that the pontine reticular formation plays a significant role in the cholinergic regulation of narcolepsy. PMID- 8008206 TI - Cholinergic mechanisms in canine narcolepsy--II. Acetylcholine release in the pontine reticular formation is enhanced during cataplexy. AB - Cataplexy in the narcoleptic canine has been shown to increase after local administration of carbachol into the pontine reticular formation. Rapid eye movement sleep has also been shown to increase after local administration of carbachol in the pontine reticular formation, and furthermore, acetylcholine release in the pontine tegmentum was found to increase during rapid eye movement sleep in rats. Therefore, in the present study we have investigated acetylcholine release in the pontine reticular formation during cataplexy in narcoleptic canines. Extracellular acetylcholine levels were measured in the pontine reticular formation of freely moving narcoleptic and control Doberman pinschers using in vivo microdialysis probes. Cataplexy was induced by the Food-Elicited Cataplexy Test and monitored using recordings of electroencephalogram, electrooculogram and electromyogram. Basal levels of acetylcholine in the microdialysis perfusates were approximately 0.5 pmol/10 min in both control and narcoleptic canines. Local perfusion with tetrodotoxin (10(-5) M) or artificial cerebrospinal fluid without Ca2+ produced a decrease, while intravenous injections of physostigmine (0.05 mg/kg) produced an increase in acetylcholine levels, indicating that the levels of acetylcholine levels measured are derived from neuronal release. During cataplexy induced by the Food-Elicited Cataplexy Test, acetylcholine levels increased by approximately 50% after four consecutive tests in narcoleptic canines, but did not change after four consecutive tests in control canines. Motor activity and feeding behavior, similar to that occurring during a Food-Elicited Cataplexy Test, had no effect on acetylcholine levels in the narcoleptic canines.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8008207 TI - Nucleus basalis lesions suppress spike and wave discharges in rats with spontaneous absence-epilepsy. AB - Cholinergic drugs were shown to affect spike and wave discharges in a selected strain of Wistar rats with generalized non-convulsive absence epilepsy, named GAERS (Genetic Absence Epilepsy Rats from Strasbourg). The involvement of cholinergic transmission from the nucleus basalis in the control of absence seizures in GAERS was investigated in the present study, by examining the effects of unilateral excitotoxic lesions of this nucleus on the occurrence of spike-wave discharges. Ibotenate (0.01 M) and quisqualate (0.03 and 0.06 M)-induced lesions of the nucleus basalis suppressed spike-wave discharges in the cortex ipsilateral to the lesion. The suppression was associated with a disappearance of both acetylcholinesterase-fibres in the cerebral cortex and choline acetyltransferase immunopositive neurons within the nucleus basalis. Concomitantly, the background electroencephalographic activity was slowed. These results suggest that cholinergic innervation of the cerebral cortex by the nucleus basalis is involved in the occurrence of generalized non-convulsive seizures, in relation to the control of cortical activation. PMID- 8008208 TI - Postnatal development of hippocampal and neocortical cholinergic and serotonergic innervation in rat: effects of nitrite-induced prenatal hypoxia and nimodipine treatment. AB - Postnatal development of ingrowing cholinergic and serotonergic fiber patterns were studied in the rat hippocampus and parietal cortex employing a histochemical procedure for acetylcholinesterase as a cholinergic fiber marker, and immunocytochemistry of serotonin for serotonergic fiber staining. The rat pups were killed at postnatal days 1, 3, 5, 7, 10, and 20. The development of cholinergic and serotonergic innervation was described and the fiber density quantified under normal conditions and after long-term prenatal anemic hypoxia induced by chronic exposure to sodium nitrite. Furthermore, a third group was studied in which the nitrite hypoxia was combined with a simultaneous treatment with the Ca(2+)-entry blocker nimodipine to test the neuroprotective potential of this drug. Quantitative measurement of fiber density from postnatal day 1 to day 20 yielded the following results: (i) both neurotransmitter systems revealed an age-dependent and an anatomically-organized developmental pattern; (ii) the serotonergic innervation of the dorsal hippocampus preceded that of cholinergic afferentation in postnatal days 1-3; (iii) prenatal hypoxia induced a transient delay in the innervation of parietal neocortex and dentate gyrus for both neurotransmitter systems, but left the innervation of the cornu ammonis unaffected; and (iv) the hypoxia-induced retardation of cholinergic and serotonergic fiber development was prevented by concomitant application of the Ca(2+)-antagonist nimodipine during the hypoxia. The results indicate that prenatal hypoxia evokes a temporary delay in the cholinergic and serotonergic fiber outgrowth in cortical target areas in a region-specific manner. The hypoxia induced growth inhibition is prevented by the calcium antagonist nimodipine, which supports the importance of the intracellular Ca2+ homeostasis of cells and growth cones in regulating axonal proliferation. PMID- 8008209 TI - Mechanisms of antihistamine-induced sedation in the human brain: H1 receptor activation reduces a background leakage potassium current. AB - Antihistamines, more formally termed H1 receptor antagonists, are well known to exert sedative effects in humans, yet their locus and mechanism of action in the human brain remains unknown. To better understand this phenomenon, the effects of histamine upon human cortical neurons were studied using intracellular recordings in brain slices maintained in vitro. Bath application of 50 microM histamine induced a depolarization which could be attributed to reduction of a background voltage-independent "leakage" potassium current: the depolarization was associated with an increase in apparent input resistance, under voltage clamp its reversal potential approximated the potassium reversal potential, and the histamine-induced current exhibited little voltage dependence. The pharmacology of the histamine-induced depolarization of human cortical neurons was studied by use of both agonists and antagonists. Depolarizing responses were blocked by the H1 antagonist mepyramine, but not by the H2 antagonist cimetidine nor the H3 antagonist thioperamide. The H3 receptor agonist R-alpha-methyl-histamine did not mimic the effects of histamine. Thus, histamine depolarizes human cortical neurons via action at an H1 receptor. These effects of neuronal histamine upon cortical neurons are likely to affect synaptic transmission in several ways. The depolarization per se should increase the likelihood that excitatory synaptic potentials will evoke an action potential. The increase in whole-cell input resistance evoked by H1 receptor activation should make the cell more electrotonically compact, thereby altering its integrative properties. We hypothesize that these mechanisms would allow histamine, acting at cortical H1 receptors, to enhance behavioral arousal. During waking when histamine release is highest, blockade of H1 receptors by systemically administered H1 receptor antagonists would be sedating. PMID- 8008211 TI - Insulin-like growth factor I-immunoreactive peptide in adult human cerebellar Purkinje cells: co-localization with low-affinity nerve growth factor receptor. AB - It has been proposed that Insulin-like growth factor I is involved in the development, growth and maintenance of the central nervous system possibly interacting with other trophic factors. High levels of insulin-like growth factor I have been detected in the cerebellum during development and adulthood suggesting a specific role for insulin-like growth factor I in this brain area. While there is ever increasing data regarding the cell types containing endogenous insulin-like growth factor I in the rat brain, no information on the human brain is yet available. In the present study we sought to analyse the precise location of insulin-like growth factor I peptide in the adult human cerebellum using a specific antiserum against recombinant human insulin-like growth factor I. After immunocytochemistry, numerous Purkinje cells exhibited intense positive staining occupying the cell soma, dendrites and dendritic spines as well as axons. Occasionally, immunoreactive Purkinje cell axons were arciform and exhibited bulbous dilatations along their proximal length. Putative recurrent collaterals of Purkinje cell axons were also insulin-like growth factor I reactive. Double-staining immunocytochemistry in the same sections consistently showed, as expected, co-expression of insulin-like growth factor I and calbindin, although a few calbindin containing Purkinje cells lacked insulin-like growth factor I immunostaining suggesting there are insulin-like growth factor I positive Purkinje cell subsets in the human cerebellum. In addition, co expression of insulin-like growth factor I and low-affinity nerve growth factor receptor-immunoreactive protein was found in a subpopulation of insulin-like growth factor I positive Purkinje cells. The results of this study prove the presence of insulin-like growth factor I immunoreactivity in a Purkinje cell subpopulation of the adult human cerebellum suggesting that insulin-like growth factor I may participate in paracrine or autocrine regulatory systems in the adult human brain. PMID- 8008210 TI - Imidazoline receptors, non-adrenergic idazoxan binding sites and alpha 2 adrenoceptors in the human central nervous system. AB - Both [3H]clonidine and [3H]idazoxan bind to alpha 2 adrenoceptors. The former also labels imidazoline receptors, and the latter non-adrenergic idazoxan binding sites. In order to investigate whether the imidazoline receptors and non adrenergic idazoxan binding sites are identical, we compared the binding characteristics of [3H]clonidine and [3H]idazoxan to these sites by radioligand binding experiments on ultra-thin slices and homogenates of human striatum. A good correlation was found between the effect of different ions on the binding characteristics of [3H]clonidine and [3H]idazoxan, and the affinities of most competing drugs. However, clonidine and rilmenidine displayed a 100- and 10-fold lower affinity, respectively, for the idazoxan binding sites than for the imidazoline receptors. Autoradiography with [3H]clonidine showed that high densities of imidazoline receptors were present in the striatum, pallidum, gyrus dentatus of the hippocampus, amygdala, and substantia nigra. Moderate densities were found throughout the cerebral cortex, thalamus and several brainstem nuclei including the nucleus olivarius inferior. Low densities were seen in the cerebellum, spinal cord and pituitary gland. As for the non-adrenergic sites labelled by [3H]idazoxan, the imidazoline receptors can be found in all major brain areas examined. However, there are some striking differences between the concentrations of imidazoline receptors and non-adrenergic idazoxan binding sites in certain brain regions. To reconcile distribution and pharmacologic data, we propose that imidazoline receptors and non-adrenergic idazoxan binding sites represent different proteins or protein complexes and that at least in the nucleus reticularis lateralis and the striatum, imidazoline receptors and non adrenergic idazoxan binding sites may be physically associated. The regional distribution of alpha 2 adrenoceptors within the human CNS was determined by quantitative autoradiography with [3H]RX821002. The highest densities of alpha 2 adrenoceptors were found in the cerebral and cerebellar cortex, and certain regions in the medulla oblongata (floor of the IV ventricle, reticular formation, hypoglossal nucleus and nucleus olivarius inferior). No alpha 2 adrenoceptors were detected in the pituitary gland. There exists no relationship between the distribution pattern of imidazoline receptors and alpha 2 adrenoceptors, indicating that these binding sites are independent from each other. PMID- 8008212 TI - Tropism of serotonergic neurons towards glial targets in the rat ependyma. AB - During development, recognition mechanisms between neurons and their targets are necessary for the formation of the neuronal network. Neural connections are synaptic or non-junctional. Both types of communication can be found between neurons and glial elements in the periventricular walls. Serotonergic fibers form synaptic contacts on the specialized ependymocytes of the subcommissural organ, a structure which forms the roof of the third ventricle at its junction with the aqueduct. A network of non-junctional fibers containing both GABA and serotonin spread between the cilia of the classical ependymocytes in the ventricles. These anatomical, morphological and biochemical features suggest a tropism and specific recognition mechanisms between glial elements and serotonergic neurons. This hypothesis can be tested by the study of the innervation of the subcommissural organ and the classical ependyma by grafted embryonic neurons after a chemical destruction of the serotonergic endogenous innervation. Solid implants or cell suspensions prepared from embryonic metencephalon were transplanted to either the third ventricle or the periventricular gray matter in 5,7-dihydroxytryptamine denervated rats. Grafted serotonergic neurons were able to reinnervate the classical ependyma and the subcommissural organ. The fibers forming the supraependymal plexus were non-junctional and contained both serotonin and GABA while those innervating the subcommissural organ formed synaptic contacts and contained only serotonin. The signals capable of inducing the ependymal innervation were specific for serotonergic neurons since catecholaminergic neurons present in the grafts were unable to innervate either classical or specialized ependymocytes. These results demonstrate that glial cells are targets for serotonergic neurons and that the morphological and biochemical characteristics of the serotonergic innervation are closely related to the target cell phenotype. PMID- 8008214 TI - Motor cortex and pyramidal tract axons responsible for electrically evoked forelimb flexion: refractory periods and conduction velocities. AB - Double-pulse methods are used here to measure the refractory periods and conduction velocities of the pyramidal tract axons which cause forelimb flexion in pentobarbital anesthetized rats. In the refractory period experiments, conditioning and test pulses were delivered to the motor cortex, the ipsilateral internal capsule, or the ipsilateral pyramid, and the maximum force exerted by the contralateral forelimb was measured at various conditioning-test intervals. The movements increased as conditioning-test interval increased from 0.5 to 1.0 ms in pyramid sites, from 0.6 to 1.5 in internal capsule sites, and from 0.6 to 2.0 ms in surface cortical sites, suggesting longer refractory periods for the substrates at more rostral sites. In cortical sites, as the conditioning-test interval increased from 4.0 to 20.0 ms, the movements decreased gradually to the single-pulse level, suggesting decreasing temporal summation at longer conditioning-test intervals. In the collision experiments, when conditioning pulses were delivered to one site and test pulses to a second site, the movements increased at conditioning-test intervals that were longer by 0.5-1.3 ms than the refractory periods in either site. This suggests that collisions occurred between orthodromic and antidromic action potentials in the pyramidal tract axons responsible for the limb movement. The collision-like increase was greater between internal capsule and pyramid than between cortex and pyramid, or between cortex and internal capsule. The estimated conduction times were 0.9-1.5 ms between cortex and pyramid, 0.4-0.8 ms between cortex and internal capsule, and 0.5-0.8 ms between internal capsule and pyramid. The range of conduction velocities, therefore, was quite narrow between all pairs (8.8-16.8 m/s). The largest pyramidal tract axons appear to be responsible for most of the force of forelimb flexion in pentobarbital anesthetized rats. PMID- 8008213 TI - Nicotinic receptor activation facilitates GABAergic neurotransmission in the avian lateral spiriform nucleus. AB - Whole-cell patch clamp recordings were performed in embryonic chick brain slices to characterize responses to nicotinic receptor activation in the mesencephalic lateral spiriform nucleus. Using intracellular recording, we previously reported the presence of functional high-affinity nicotinic sites in this nucleus that are insensitive to blockade with kappa- and alpha-bungarotoxin. We now report that nicotinic agonists not only produce an inward current in these cells, but also elicit a massive increase in the frequency of spontaneous postsynaptic currents without changing the amplitude distribution or risetime and decay kinetics of these events. The nicotinic receptor antagonist, dihydro-beta-erythroidine, blocks both the postsynaptic inward current and the enhancement of spontaneous postsynaptic currents. The spontaneous currents reverse at or near the chloride ion equilibrium potential and are completely blocked by 10 microM bicuculline, indicating that these events are likely to be GABAergic inhibitory postsynaptic currents. The nicotinic agonist-induced enhancement in inhibitory postsynaptic current frequency is blocked by 1.0 microM tetrodotoxin, demonstrating that the effect is mediated through the activation of voltage-dependent sodium channels. Nicotinic receptors are widely distributed in the central nervous system and in some cases are thought to modulate the release of various neurotransmitters. Our results show that activation of nicotinic receptors facilitates inhibitory neurotransmission in the avian lateral spiriform nucleus by increasing the frequency of spontaneous GABAergic postsynaptic currents. These data support a role for nicotinic receptors in the regulation of GABA release from nerve terminals in this nucleus. PMID- 8008215 TI - Shaping static elbow torque-angle relationships by spinal cord circuits: a theoretical study. AB - Static torque-angle relationships (invariant characteristics) as measured by Feldman [Feldman A. G. (1980) Neuroscience 5, 81-90] at the human elbow joint for constant descending excitatory drive have a monotonic convex shape determining joint angle-dependent stiffness. In contrast, for constant activation of elbow flexors, the torque increases, peaks and decreases again with increasing angle because of related moment arm alterations [Hasan Z. and Enoka R. M. (1985) Expl Brain Res. 59, 441-450]. Conversion of such constant-excitation torque-angle shapes into an invariant characteristic might result from action of the stretch reflex which adds excitation with increasing joint angle. To test whether a simple linear model of the stretch reflex could convert constant excitation torque-angle relationships into invariant characteristics, the following assumptions were made. (1) Muscle fibre length increases linearly with joint angle. (2) Reflex muscle excitation (electromyogram) is linearly related to muscle (fibre) length. With these assumptions, invariant characteristic shape cannot be derived from constant excitation torque-angle relationships because it would be sigmoid at low and nearly straight at large joint angles, whilst real flexor invariant characteristics are more convex at large than small angles. It is suggested that recurrent inhibition via Renshaw cells contributes to bend the invariant characteristics into their right shape. Renshaw cells show a nonlinear saturating dependence on motor axon input rate and amount of excitation, i.e. number of active axon collateral synapses. These relationships can contribute to shape motoneuron output so as to yield convex invariant characteristics. Whilst it is not quite clear whether the gain of recurrent inhibition from and to skeleto-motoneurons is high enough to co-determine the invariant characteristic shape significantly, recurrent inhibition of Ia inhibitory interneurons mediating reciprocal inhibition between antagonists is supposed to be quite strong and may influence joint stiffness by interacting with reciprocal inhibition. The arguments presented here extend those of Feldman and co-workers concerning the role of recurrent inhibition and in addition provide a possible explanation for the functional role of mutual inhibition between Renshaw cells. Together with reflex feedback, recurrent inhibition thus contributes to fine-regulate force output and joint stiffness. To account for this cooperation and to make another step towards a general theory of spinal cord circuits, major traits of a new concept are briefly outlined. PMID- 8008217 TI - Permeation of proteins from the blood into peripheral nerves and ganglia. AB - We have attempted to resolve apparently conflicting observations of previous investigators regarding the penetration of proteins into peripheral ganglia and nerves of the rat. Horseradish peroxidase, which is largely cleared from the blood and extracellular fluids in less than 30 min, entered all the extracellular spaces of ganglia, including the clefts between glial cells and neurons, but it did not enter the endoneurium. Rhodamine B-conjugated bovine albumin quickly entered sensory and sympathetic ganglia, but its penetration into avascular enteric nervous tissue was arrested at the outer margin of each myenteric and submucosal ganglion. If injected daily for a week, this fluorescent protein was seen also in the endoneurium, but it was still absent from enteric ganglia. The failure to enter enteric ganglia may have been due to the entrapment of aggregates of dye-labelled albumin molecules in the basal lamina that encloses the enteric nervous system. Extracellular endogenous albumin immunoreactivity was seen in all parts of peripheral nerves and in all types of ganglion. Some neuronal perikarya contained albumin-immunoreactive material; the strongest staining was in enteric neurons. Albumin may reach these cell bodies by retrograde axonal transport from peripheral terminals. We conclude that all the extracellular spaces of the rat's peripheral nervous system are accessible to plasma proteins, though diffusion occurs more slowly into the endoneurium than into ganglia. PMID- 8008216 TI - Differential distribution of messenger RNAs for cathepsins B, L and S in adult rat brain: an in situ hybridization study. AB - The cysteine lysosomal proteases comprise a large family of highly conserved enzymes which are essential for intracellular protein turnover. These proteases are very efficient in their ability to degrade components of the extracellular matrix, and have been implicated in processes of cell growth, malignant transformation and inflammation. There is also a growing body of evidence for their involvement in the metabolism of the amyloid precursor protein. The production of insoluble beta A4 amyloid peptide is thought to be one of the key events that lead to the development of Alzheimer's pathology. To see the physiological role these enzymes play in the brain, we studied the relative abundance and distribution of the messenger RNAs for three lysosomal cysteine proteases, cathepsins B and L and cathepsin S, by in situ hybridization histochemistry in rat brain. All three enzymes are capable of degrading components of the extracellular matrix but they have different substrate preferences and resistances to neutral pH. We found that the mRNAs for cathepsins B, L, and S have different expression patterns in brain. Cathepsin B mRNA shows the highest level of expression. It has a wide distribution, and is preferentially expressed in neurons. The expression patterns of cathepsin B and cathepsin L mRNA overlap in many brain regions; in some areas they complement each other. Cathepsin B and L mRNAs are highly expressed in the choroid plexus, a structure that is instrumental in brain development. Both transcripts are also abundant in the neuropeptide synthesizing hypothalamic nuclei. Cathepsin S mRNA has wide expression pattern throughout brain, in grey and white matter. A great number of cells that express cathepsin S have microglial morphology. Regions that are known to contain the highest amounts of the amyloid precursor protein express highest levels of cathepsin B and cathepsin L mRNA. Also, all three transcripts are highly represented in regions that are most prone to degeneration in Alzheimer's disease. These results suggest a role for these lysosomal hydrolases released from degenerating cells in the development of Alzheimer's pathology. PMID- 8008218 TI - Vimentin-positive rosary-bead-like formations in the rabbit superior colliculus during postnatal development. AB - Strings of vimentin-positive rosary-bead-like formations in the rabbit superior colliculus were studied. The size and distance between beads varied from one string to another, and within a given string. The formations were similar in number and distribution in the two superior colliculi. Successions of beads were found mainly in the medial and deep layers, and represented not more than 1% of the radial glial fibers. The strings were in continuity at deep levels with segments of varicose fibers of radial glia, which in turn were continuous with fibers of normal appearance. These observations suggest a temporal sequence of evolution, starting with the normal radial glial fiber, which acquires swellings that in turn give rise to discrete beads; in subsequent stages, the beads become smaller and more widely separated. In the newborn rabbit, these formations are seen mainly in laterobasal regions of the superior colliculus, and spread throughout the colliculus by the end of week one of postnatal life, becoming more numerous in medial regions. We suggest that these formations represent a mechanism of removal of at least part of the radial glial fibers, and discuss the possible relation between these formations and the transformation of radial glia into astrocytes. PMID- 8008220 TI - Letter of retraction. PMID- 8008219 TI - Ultrastructural features of the isolated guinea-pig brain maintained in vitro by arterial perfusion. AB - The morphological features of cerebral tissue in the isolated guinea-pig brain maintained in vitro by arterial perfusion are described. Light and electron microscopic analysis of the thalamus, the somatosensory cortex and the limbic cortices (hippocampus, piriform and entorhinal cortices) was performed after different periods of incubation in vitro (1, 7 and 12 h), in parallel with an electrophysiological study. The morphological analysis showed that neuronal elements retained their normal appearance at both cellular and subcellular level in the examined brain regions up to an incubation period of 12 h. Immunoreactivity for GABA was also preserved for up to 12 h of in vitro perfusion. Vasogenic edema and perivascular extracellular swelling appeared after 7 h, together with signs of progressive astrocytic deterioration. These findings show that normal electrophysiological recordings correlate with good anatomical preservation of the isolated guinea-pig brain preparation after prolonged times of arterial in vitro perfusion. PMID- 8008221 TI - Diagnostic criteria for migraine. A validity study. AB - To identify the optimum combination of symptoms for the International Headache Society (IHS) diagnostic criteria for migraine, the criteria were systematically assessed for validity using an epidemiologic sample from Zurich, Switzerland. The indicators of validity used included subjective distress, occupational impairment, family history of migraine, and treatment. The symptoms that provided the best discrimination between migraine and other headache subtypes were photophobia, phonophobia, and osmophobia, in combination with gastrointestinal symptoms. The evaluation of the validity of the IHS classification of migraine is impeded by several factors, including: the presence of multiple headache syndromes within an individual, the tendency for headache characteristics to change over a lifetime, the effects of headache treatments in obscuring syndromes, and the lack of generalizability of findings based on clinical samples. The methods used in this study serve as a model for applying statistical techniques for evaluating the validity of diagnostic criteria. The findings, however, should be replicated in additional studies to determine their generalizability to specific demographic and clinical subgroups. PMID- 8008222 TI - Migraine prevalence. A review of population-based studies. AB - Obtaining accurate and reliable information on the prevalence of migraine is essential to understanding the burden it places on society. Although the epidemiology of headache has been described in more than 50 population-based studies, only 24 of these have described the gender- and age-specific prevalence of migraine. Essentially five different case definitions have been used in these studies. Variation in the prevalence of migraine among studies is largely due to differences in case definition and in the age and gender distribution of study populations. Among four recent studies that used the diagnostic criteria of the International Headache Society (IHS), a coherent picture emerges. The prevalence of migraine is approximately 6% among men and 15 to 17% among women. Prevalence varies by age, increasing to about age 40 years and declining thereafter in both men and women. The gender ratio also appears to vary by age, increasing from menarche to about age 42 years and declining thereafter. Although the use of the IHS criteria has resulted in a more coherent picture across population-based studies, efforts must be made to assess the reliability and validity of these criteria in population-based samples. PMID- 8008223 TI - Migraine heterogeneity. Disability, pain intensity, and attack frequency and duration. AB - Data from population-based studies are summarized to characterize the full range and variability of the impact migraine has on the individual. Despite differences in methods and data collection in population-based studies describing disability, pain intensity, and attack frequency as well as the duration of migraine and other headaches, several patterns emerge. On average, migraine headaches are more disabling, more painful, and longer in duration than other types of headaches. Females report more pain and disability with headache than do males. Although disability measurements are important in demonstrating the effect of headache on both the individual and society, actual measurements often fall short. Most studies use only workdays lost as the sole measure of disability. Most migraineurs do not miss work while experiencing a headache; instead, they attempt to function on the job, with considerably reduced effectiveness. Computing only workdays lost does not account for impairment at work nor does it show the impact of migraine on other aspects of life. In addition, evidence suggests the presence of a pain intensity threshold for disability. Headache-related pain intensity below the threshold is not associated with disability. Despite the threshold of pain intensity for disability, a significant proportion of migraine sufferers report levels of pain intensity above the threshold in the absence of work related disability. The grading of headache severity should be a composite that would permit a more complete image of the heterogeneity of migraine's effects and a more accurate idea of the need for healthcare services. This composite should include two areas: (1) more complete measures of life impact, encompassing daily activities in a number of domains, including work, family, and social activities; and (2) an assessment of pain intensity and attack frequency. PMID- 8008225 TI - Migraine. Patterns of healthcare use. AB - Data on use of healthcare from several sources reflect low rates of consultation among migraineurs, many of whom are severely disabled, and limited detection of migraine among those seeking care. Most migraineurs who seek medical care are motivated by the need for pain relief and are initially seen by a general practitioner. Use of healthcare seems to follow a pattern, with a maximum use of services and technology within the first year, followed by a precipitous decrease over the ensuring years. The use of services appears to be concentrated among a small proportion of the migraineurs who seek care. In total volume, the migraineur uses two to five times more healthcare services than nonmigraineurs, reflecting the contribution of comorbidities and help-seeking behavior. Use of emergency departments and sophisticated diagnostic testing appears to be greater in the United States than in other countries. Hospitalization of the migraineur is uncommon and remains costly. PMID- 8008226 TI - The economic cost of migraine. Present state of knowledge. AB - The costs of medical care and lost productivity associated with migraine headache impose an economic burden on society. Knowledge of the costs that can be attributed to migraine would provide a basis for evaluating alternative diagnosis and treatment strategies. The most widely used approaches to analyzing the cost of illness analysis are the willingness-to-pay and human capital methods. Using these as a framework, all recent published studies (from 1980 to the present) relevant to the economic cost of migraine were reviewed. The literature reviewed demonstrates that the economic burden of migraine headache is substantial. To estimate the cost of migraine to society more precisely, data are needed on incidence and prevalence among carefully selected samples representative of the underlying population. Use of medical care must be expressed as units of specific types of services rendered over known periods. Health insurance coverage, an important determinant of access to care, should also be known. Absenteeism and work losses must be linked to occupation and earnings levels. PMID- 8008224 TI - Assessing headache severity. New directions. AB - Headache is a heterogeneous condition that varies widely in global severity and in severity of individual attacks. Whereas recent efforts have focused on improving the diagnostic criteria for classifying headache, less effort has been directed toward developing reliable, valid, and clinically useful methods of assessing the impact or severity of headache. Existing measures of severity include one or more of the following weaknesses: (1) only pain intensity is assessed or the measure is incomplete in other ways, (2) measures have little or no prognostic value for relevant outcomes, (3) the reliability or the validity of the measure has not been assessed, or (4) the measure is too cumbersome for clinical practice or field research. We describe a brief, simple method for grading the severity of headache, the Chronic Pain Index, which assumes that a continuum of pain intensity and disability is the underlying dimension of severity. Along this continuum, lower levels of severity are differentiated by pain intensity and higher levels by interference with function. The prognostic value of the results from a seven-item questionnaire for grading headache severity is compared with that of alternative measures. The Chronic Pain Index showed the strongest independent cross-sectional and prospective correlation with measures of headache impact, depression, and use of healthcare services. These results support the potential utility of brief methods of assessing headache severity and exemplify the importance of including measures of interference with function when assessing severity. PMID- 8008227 TI - Migraine classification and diagnosis. International Headache Society criteria. AB - In 1988, the International Headache Society (IHS) classification committee published operational diagnostic criteria for a broad range of headache disorders, including migraine. These criteria have been translated into more than 10 languages, providing uniform terminology for clinical practice, multinational clinical trials, and biologic and epidemiologic research. The criteria have also been evaluated in a limited number of field studies intended to address their reliability, validity, comprehensiveness, and generalizability. The IHS criteria for migraine provide one method for targeting a group of headache patients in need of care. PMID- 8008228 TI - Migraine. Identifying and removing barriers to care. AB - The high levels of pain and disability associated with undiagnosed migraine or inadequate treatment of migraine offer a potential target for healthcare intervention. Both the individual patient and society are affected by decisions regarding which migraine sufferers are most in need of medical care. Pain is the most important symptom for the individual patient, but disability may be the most important consequence of migraine for an increasingly cost-conscious society. These two perspectives are the components of a migraine severity or impact measure being developed to define migraine sufferers most in need of care. The criteria for developing screening programs provide a context for evaluating healthcare interventions for migraine. Barriers to effective care occur on at least three levels: many people with migraine do not consult doctors; consulters may not receive the correct diagnosis; and even when the correct diagnosis is made, many migraineurs do not receive effective treatment. Screening and impact measures may help both to improve diagnosis and to determine which migraineurs are most in need of care. Public and physician education, screening, and impact measures might circumvent many of the barriers to effective care for people with migraine. PMID- 8008229 TI - Report on management of renal failure in children in Europe, XXIII, 1992. PMID- 8008230 TI - Report on management of renal failure in Europe, XXIII. PMID- 8008231 TI - Plasticity in mesencephalic and retinal polarity formation in avian embryos. AB - Polarity and its plasticity in the avian mesencephalon and the retina are reviewed. Rostrocaudal polarity of the tectum (dorsal mesencephalon) is revealed by the gradient of engrailed gene expression, by its cytoarchitecture, and by positional specification of tectal cells which retinal fibers read to find their targets. In the ventral mesencephalon, the polarity is revealed by directional growth of tectofugal axons. To examine the plasticity in rostrocaudal polarity, rostrocaudal orientation of the mesencephalon was surgically reversed on E2. Rostrocaudal polarity of the reversed mesencephalon was all adjusted to the host pattern. This suggests that the mesencephalic polarity is not fixed on E2 and is established under environmental influences. Retinal polarity is revealed by the distribution of certain molecules, by retinal structures, and by the retinotectal projection pattern. Retinal structures and retinotectal projection pattern were kept as in the original if retinal primordium was rotated or partially excised after stages 12-14 of Hamburger and Hamilton. The location of an optic fissure and the retinal fiber pattern were adjusted to those of normal eyes when the rotation was performed before stage 12, therefore the retinal polarity was supposed to be plastic before stage 12 and to be fixed around the stages 12-14 under environmental influences. PMID- 8008232 TI - PCPA reduces both monoaminergic afferents and nonmonoaminergic synapses in the cerebral cortex. AB - In order to examine the possible trophic, nontransmitter role of monoaminergic fibers in the adult CNS, synaptic structures were examined in different laminae of the somatosensory cortex of the rat following a p-chlorophenylalanine (PCPA) induced decrease of monoamine. Synaptic densities were reduced in a dose dependent fashion by 30-50% in the target area of monoamine fibers following four injections of PCPA made over a 1-week period. Although serotonin- and tyrosine hydroxylase-immunopositive profiles were frequently observed in all laminae of the cerebral cortex, only a few such profiles had the morphology of synapses. Therefore, virtually all of the reduction in synaptic structures following PCPA treatment involved nonmonoaminergic fibers. PMID- 8008233 TI - Firing of neurons in the preoptic/anterior hypothalamic areas in rat: its possible involvement in slow wave sleep and paradoxical sleep. AB - The basal forebrain including the preoptic area and anterior hypothalamus plays an important role in regulation of slow wave sleep. To examine whether this area is concerned also in a neural mechanism of paradoxical sleep, single neuronal activity in and around the preoptic area along with cortical EEG and neck EMG was recorded in undrugged, 12-h sleep-deprived rats whose head was fixed painlessly. The neurons whose activity was recorded during all states of sleep and wakefulness (n = 98) were classified into following 5 groups according to their firing behavior in relation to sleep-waking states. (1) Neurons most active during paradoxical sleep (n = 26). (2) Those most inactive during paradoxical sleep, some of which were inactive also during slow wave sleep (n = 16). (3) Those specifically active during slow wave sleep (n = 14). (4) Those less active during slow wave sleep than during wakefulness and paradoxical sleep (n = 9). (5) Those whose activity showed no clear correlation with the sleep-waking states (n = 33). About one third of neurons in each of groups (1) to (4) began to increase their sleep-related activity in advance of the shift of sleep/wakefulness state recognized in EEG. These results suggest that the preoptic and anterior hypothalamic areas are involved, at least in rats, in regulation of not only slow wave sleep but also paradoxical sleep. PMID- 8008234 TI - Noradrenergic inputs to sleep-related neurons in the preoptic area from the locus coeruleus and the ventrolateral medulla in the rat. AB - Responses of sleep-related neurons in the preoptic area (POA) to stimulation of the locus coeruleus (LC) and the ventrolateral medulla (VLM), components of the reticular activating system, were recorded in the unanesthetized, head-restrained rat. Single-pulse stimulation of the LC and the VLM, respectively, inhibited 50% and 54% of 30 sleep-active neurons and excited 47% and 67% of 34 waking-active neurons. The remaining neurons were mostly unaffected. Seventy-three neurons that were not related to a sleep-wake state were mostly (i.e., 73-80%) unresponsive to stimulation. The high incidence of responses by sleep-related neurons suggests that neural inputs from the LC and VLM regulate the hypnogenic mechanisms in the POA. Stimulation of the LC antidromically activated 15% of sleep-active neurons and 11% of waking-active neurons. Thus, some of the sleep-related neurons in the POA may regulate LC neurons. In a later stage of the experiment, we used isoflurane-anesthetized rats that had been used for recording sleep-related neurons. Antagonists for adrenoceptors at a concentration of 10 microM were applied to neurons through a multibarrel micropipette to examine the involvement of noradrenaline in the responses as a neurotransmitter. Application of the alpha 2-blocker, yohimbine, attenuated the inhibitory responses in all 7 neurons tested. The beta-blocker, timolol, and the alpha 1-blocker, prazosin, did not alter any of the inhibitory responses. On the other hand, timolol attenuated the excitatory responses in 4 of 7 neurons, and prazosin attenuated the excitatory responses in 5 of 12 neurons. Yohimbine did not affect the excitatory responses. Thus, the LC and the VLM probably inhibit sleep-active neurons through alpha 2 adrenoceptors and excite waking-active neurons through either beta- or alpha 1 adrenoceptors. PMID- 8008235 TI - Differential expressions of the topoisomerase II alpha and II beta mRNAs in developing rat brain. AB - Distributions of the topoisomerase II alpha and II beta mRNAs were examined in the developing rat brain, by in situ hybridization with isoform-specific oligonucleotide probes. Intense signals for the topoisomerase II alpha mRNA were detected in the ventricular zone of each brain region at embryonic day 13-15 (E13 E15), and in the external granular layer of the cerebellum at postnatal day 7-14 (P7-P14). Thereafter, the signals rapidly decreased in levels and eventually disappeared from respective regions. Administration of bromodeoxyuridine (BrdU) into embryos at E13 showed that the topoisomerase II alpha mRNA was expressed in the BrdU-incorporated region and its ventricular side of the neural wall, suggesting that transcription of this isoform occurs in neurons from S-phase through M-phase. On the other hand, the topoisomerase II beta mRNA was distributed throughout the brain from E13 through P21, irrespective of the ventricular and mantle zones. Signal levels of the topoisomerase II beta mRNA were much stronger during early developmental stages than at mature stages in various brain regions. The characteristic and differential spatio-temporal expressions suggest that the topoisomerase II alpha is involved in the proliferation, while the topoisomerase II beta is closely related to differentiation and maturation of neurons. PMID- 8008236 TI - Anti-ubiquitin immunoreactivity associates with pyramidal cell death induced by intraventricular infusion of leupeptin in rat hippocampus. AB - Pathological studies on several neurodegenerative diseases including Alzheimer's disease have revealed common deposition of ubiquitin in many inclusion bodies. This implies a possible association of ubiquitin with neurodegeneration. To address this possibility, we examined histochemically the effect of intraventricular infusion of leupeptin, a thiol proteinase inhibitor, which is known to elevate anti-ubiquitin immunoreactivity in rat Purkinje cells. In the leupeptin-infused rat, an intense anti-ubiquitin immunoreactivity in the cytoplasm of neurons occurred not only in cerebellar Purkinje cells but also elsewhere in a wide area of the rat brain. The increase in the immunoreactivity was followed by a gradual depletion of pyramidal neurons in the hippocampal CA1 and CA3 subfields. The immunoreactive neurons disappeared concurrently. The number of anti-ubiquitin immunoreactive neurons was negatively correlated with that of surviving neurons when the duration of leupeptin infusion was varied. These results suggest that increased anti-ubiquitin immunoreactivity associates with neuronal death in leupeptin-treated rat brain. PMID- 8008237 TI - Effect of axotomy on nitric oxide-dependent cyclic GMP production of rat superior cervical sympathetic ganglia in response to norepinephrine. AB - Cyclic GMP (cGMP) production in superior cervical sympathetic ganglia (SCG) isolated from rats was markedly enhanced (approx. 4.5-fold) by the addition of L arginine (L-Arg, 100 microM) plus an inhibitor (3-isobutyl-1-methylxanthine) for cGMP hydrolytic enzyme during in vitro aerobic incubation at 37 degrees C for 10 min. This accelerated accumulation of ganglionic cGMP was effectively reversed by approximately 50% when NG-monomethyl-L-arginine (L-NMMA, 50 microM), a compound that inhibits nitric oxide (NO) synthesis from L-Arg, was further added to the medium. These observations imply that cGMP production with possible involvement of a mechanism depending on NO synthesis may be functionally operating in the ganglionic tissue. Application of norepinephrine (NE, 50 microM) with pargyline, a monoamine oxidase inhibitor, to the medium also elevated the ganglionic cGMP level at a magnitude comparable to that shown by L-Arg addition, while co addition of L-NMMA largely (approx. -60%) eliminated the NE-induced increase in ganglionic cGMP formation. In axotomized SCG one week prior to examination, where sympathetic neurons were degenerated and reactive proliferation of glial cells was in progress, augmented stimulatory effect (more than 8-fold) of NE on cGMP production was seen compared to that caused in unoperated ganglia or in SCG 1 week following denervation, where preganglionic cholinergic nerve terminals were destroyed. When axotomized SCG were transferred to in vitro incubation conditions, addition of an alpha-1 adrenergic antagonist, prazosin (1 microM) to the medium virtually reduced the accelerative effect of NE to less than 25% of the NE-induced cGMP level in the tissue.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8008238 TI - Postnatal development of the rat corticospinal tract, with special reference to confocal laser scanning microscopy of growing axons. AB - The corticospinal tract within the spinal cord of the neonatal rats, ranging from postnatal day 1 (P1) to P11, was investigated by using anterograde labeling with DiI optimized by confocal laser scanning microscopy. This method enabled us to observe a thick section containing a large population of the labeled axons and to acquire fine structure images with sufficient resolution. As advantages, novel views of diversity emerged in the developing axons and their collaterals. First, the individual parent axons showed unrestrained trajectories within the main bundle which constantly occupied the ventral part of the dorsal column. Second, there was an aberrant bundle which ran ventrally apart from the main bundle and converged into it. Third, several projection collaterals branched from the parent axons and left the main bundle in various directions, whereas the majority of them branched off at approximately a right angle. In addition, the main bundle consisted of a small number of pioneer axons and numerous follower ones. The pioneer axon tips were first found in the cervical level on P1, in the thoracic level on P2, in the lumbar level on P5 and in the sacral level on P7. The follower axon tips were observed in a wide range away from the pioneer tips to just behind them. Projection collaterals were arborized within the gray matter and their arbors entered the dorsal horn, the intermediate substance or the ventral horn in the transverse plane. PMID- 8008239 TI - Sex differences in binding of human growth hormone to rat brain. AB - The binding of 125I-human growth hormone (125I-hGH) to membranes from female and male rat brain was studied. The binding was time-, pH- and protein concentration dependent. The binding capacities calculated for the hormone were higher in the female brain (12.1 fmol/mg protein) than in the male brain (4.5 fmol/mg protein). In the female brain, saturation isotherms yielded dissociation constants (Kd) of 6.2 x 10(-10) and 4.5 x 10(-8) M and maximal binding (Bmax) of 2.9 and 8.4 fmol/mg protein for the high and low affinity binding sites, respectively, and in the male brain a Kd of 2.3 x 10(-9) M and a Bmax of 3.5 fmol/mg protein. Displacement studies indicated that in the female brain the binding of 125I-hGH was inhibited in a dose-dependent manner more potently by lactogenic than by somatogenic hormones. The rank order of potencies of these hormones to inhibit the binding of 125I-hGH was hGH > hPRL > rPRL > oGH > rGH. However, in the male brain the inhibition of 125I-hGH binding was found to be most pronounced by somatogenic hormones with the rank order of hGH > oGH > rGH > hPRL > rPRL. These findings indicate the presence of specific binding sites for hGH in the rat brain. The level as well as the properties of these sites vary in the two sexes, with higher levels in the female brain as compared to the male brain. Moreover, these sites display predominantly lactogenic characteristics in the female brain and almost exclusively somatogenic characteristics in the male brain. PMID- 8008240 TI - Immunohistochemical demonstration of ganglioside GD3 in the central nervous system. AB - Immunohistochemical staining for GD3 in adult rat brain was carried out using mouse IgM anti-GD3 monoclonal antibody (DSG-1). Neuronal cells in the cerebral cortex, striatum, hippocampus and various nuclei of the thalamus were immunoreactive. In the cerebellum, Purkinje cells, granule cells and also basket cells were immunoreactive. However, astrocytes and oligodendrocytes in the cerebrum and cerebellum were not immunoreactive. The GD3 immunoreactivity was located in the cytoplasm. These findings are of considerable interest, being the first reported demonstration of GD3 in the adult rat brain. The implications and possible significance of the presence of GD3 are discussed. PMID- 8008241 TI - Electrical activation and inhibition of respiration in vitro. AB - The present studies employed the neonatal rat rib-attached brain stem-spinal cord preparation to examine the effects of electrical stimulation of the medulla and the pons on respiratory-like activity. The investigation focused on determining whether electrical stimulation of the medulla can be used to modulate respiratory like activity, whether electrical stimulation of the pons can inhibit respiratory like activity, and how the preparation responds when both the medulla and the pons are stimulated simultaneously. The results suggest that: (1) stimulation of the ventromedial part of the medulla entrains the onset and the frequency of respiratory-like electromyographic (EMG) bursting most effectively and drives the respiratory rate as high as 0.4 Hz; (2) both ventromedial and ventrolateral pontine stimulation inhibited respiratory-like EMG bursting, but only ventrolateral pontine stimulation was followed by post-stimulation inhibition; (3) when the medulla and the pons were stimulated simultaneously, pontine stimulation-induced inhibition outweighed medullary stimulation-induced activation and resulted in a temporary cessation of respiratory-like EMG bursting. PMID- 8008242 TI - Miniature endplate currents at the newly formed neuromuscular junction in Drosophila embryos and larvae. AB - Miniature endplate currents (mepcs) were recorded in embryos and larvae of Drosophila melanogaster with the patch clamp technique in the whole cell configuration from abdominal ventral oblique muscles. Shortly after nerve-muscle contacts (16 h after egg laying) mepcs were small and infrequent. The mean amplitude of mepcs increased abruptly during late embryonic stages but did not change any further up to second instar larvae. The amplitude distribution of mepcs was skewed toward larger amplitudes and changed drastically to a more broader distribution at the time of hatching, but did not change any further. These muscle cells were found to be electrically coupled to those in the rostral neighbor segment. The synaptic current has a fast rising phase and decayed with a single exponential throughout the developmental period examined. The decay time constant increased with amplitude but the rise time did not. Neither the rise time nor the decay time constant changed with development. Many synaptic currents decayed in a stepwise manner revealing underlying single channel events. Two discrete steps were discerned, with amplitudes of about 7.6 and 16 pA at -60 mV. These two types of channels were observed throughout the stages examined. PMID- 8008243 TI - Polyamines promote neurite elongation of cultured rat hippocampal neurons. AB - The effects of spermine, spermidine and putrescine on the survival and morphology of hippocampal neurons obtained from rat embryos were investigated using low cell density culture. The number of surviving neurons gradually decreased in the control cultures, while addition of spermine significantly promoted neuronal survival. The survival-promoting effect of spermine was seen maximally at a concentration of 10(-8) M. On the other hand, spermidine and putrescine showed no significant effect on neuronal survival. The axon length of neurons cultured in the presence of spermine was significantly longer than that in the medium with no added spermine, indicating that spermine promotes process elongation. The concentration-effect curve for spermine was bell-shaped with the maximum effect at a concentration of 10(-8) M. However, the number of processes per soma, the elongation of dendrites and the process branching in axons were not significantly affected by the presence of spermine. Addition of spermidine and putrescine also promoted the axon elongation of cultured neurons, without affecting the branching number. The effects of spermidine and putrescine on neuronal growth were very similar to that of spermine in terms of the effective concentrations and the patterns of morphological changes. Since spermine specifically promoted neuronal survival while three polyamines affected the neuronal morphology in a similar manner, it is possible that the effects of polyamines on neuronal survival and neurite elongation are mediated by different mechanisms. PMID- 8008244 TI - 5-HT1A receptor-mediated inhibition of N-type calcium current in acutely isolated ventromedial hypothalamic neuronal cells. AB - The effects of serotonin (5-hydroxytryptamine: 5-HT) and 5-HT1A agonist on voltage-gated calcium channels (VGCCs) in acutely isolated ventromedial hypothalamic (VMH) neuronal cells were studied using whole-cell configuration of the patch-clamp technique. 5-HT at 10 microM inhibited inward calcium current reversibly in 80% of cells. This inhibition was specific to N-type current. Because pindolol blocked the effect of 5-HT and 8-hydroxy-2-(di-n propylamino)tetralin (8-OH-DPAT) mimicked the effect of 5-HT, the inhibitory effect of 5-HT appeared to be mediated via the 5-HT1A receptor. In the fura-2 fluorometry method, 8-OH-DPAT attenuated the [Ca2+]i increase induced by the depolarization stimulus of 50 mM K+. These results indicate that 5-HT suppresses Ca2+ entry through N-type channels in the VMH neurons via the 5-HT1A receptor and that the stimulating effect of 8-OH-DPAT on feeding behavior may be mediated by the blocking of Ca2+ entry through N-type channels. PMID- 8008245 TI - Effects of nervous mutation on Purkinje cell compartments defined by Zebrin II and 9-O-acetylated gangliosides expression. AB - The cerebellum is organized into a series of parasagittally aligned bands which are well delineated in the adult mouse by the largely complementary immunostaining of Purkinje cell groups with the monoclonal antibodies Zebrin II (ZII; antigen: aldolase C) and P-path (antigen: 9-O-acetyl gangliosides). We examined the effect of nervous mutation on compartmental organization using these markers and an antibody to calbindin. In nervous mutant, up to 90% of Purkinje cells die in late postnatal development. The size of the cerebellum is about half that of normal, and caudal lobules appear to decrease in size more than anterior ones. Surviving Purkinje cells corresponded to P-path positive ones that were concentrated in two bilateral bands in the vermis and in medial portions of the hemispheres. Only small numbers of ZII positive cells remained, confirming the report by Wassef et al. with Zebrin I antibody. They were primarily located in caudal lobules IX, X and a portion of lobule IV, paraflocculus and flocculus, and their immunoreactivity was weak compared to that of normal. ZII positive cells are dominant in these caudal lobules, while P-path positive cells dominate in rostral lobules in normal mice, and the similar tendency remains in mutant. Thus, the nervous gene action respects not only sagittal compartments delineated by two antibodies, but also rostro-caudal gradient. The cause of the dominant survival of P-path positive cells awaits future study. PMID- 8008247 TI - Social environment affects synaptic structure in the glomerulus of the accessory olfactory bulb of the hamster. AB - The accessory olfactory bulb (AOB) is the primary center of the vomeronasal chemosensory system. The effects of differential rearing on the numerical density and size of synapse as well as neuronal size were examined in the AOB of adult hamster. At 30 days from birth, male littermates were assigned to one of three experimental conditions. (1) the IC (isolated condition), where a male animal was housed alone, (2) the NC (neighbor condition), where one male was separated from two females by wire shields, and (3) the SC (social condition), where two males and two females were housed together. After 2 months of differential rearing, the AOBs of male littermates from each experimental set were prepared for morphological examination. The lengths of synaptic contact zones and the density of synapses in the glomeruli of the AOB as well as the area of somata of mitral/tufted cells were measured with an image analyzer. The synaptic contact zone was longer in the SC compared with both the IC and the NC while there was no difference in the synaptic density among the three groups. The somal area of mitral/tufted cells was larger in both the SC and the NC compared with the IC. These results indicate that the exposure to different rearing conditions induces differential morphological changes in both synapses and somata in the AOB of adult hamster. PMID- 8008246 TI - Distribution of Fos-like immunoreactivity in the auditory pathway of the Sprague Dawley rat elicited by cochlear electrical stimulation. AB - Fos-like immunoreactivity (FLI) was mapped in the auditory pathway of Sprague Dawley rats in response to unilateral electrical stimulation of the cochlea implanted with two stimulating electrodes. Densely packed FLI neurons were widely distributed in the dorsal cochlear nucleus (more ipsilaterally than contralaterally), while FLI neurons were rare in the posteroventral cochlear nucleus and virtually absent in the anteroventral cochlear nucleus. Sparse FLI was detected in the superior olivary complex, the pontine nuclei and the ipsilateral dorsal nucleus of the lateral lemniscus, whereas the contralateral dorsal nucleus of the lateral lemniscus was moderately labeled. In the inferior colliculus, the pattern of FLI was similar on both sides, restricted mainly to its dorsal and external cortices. At the thalamic level, FLI neurons were seen in the dorsal and medial divisions of the medial geniculate body as well as in the peripeduncular nucleus. A significant increase of FLI was observed in the temporal cortex. This study demonstrates the presence of selective functional changes along the auditory pathway elicited by electrical stimulation of the cochlea, as revealed by FLI. PMID- 8008248 TI - Properties of the 'neutral zone' explain polarity of retinal spreading depression. AB - Retinal spreading depression was evoked using low Cl- Ringer's solution and the concomitant field potentials (spreading depression potential; SDP) were recorded. The polarity of the transretinally recorded SDPs was not consistent among animal species. The SDPs recorded from carp and frog were receptor side negative, while chick and cat induced receptor side positive SDPs. According to the K+ hypothesis, the retinal SDP is generated by Muller cells responding to an increase in the extracellular K+ concentration in the inner plexiform layer. In order to clarify the relationship between the K+ increase and the polarity of the SDP, a high-K+ solution was injected at various retinal depths and the evoked potential was recorded transretinally. The neutral zone within the retina, where a change in the extracellular K+ concentration produces no net potential difference, was revealed to be near the proximal end of the retina in carp and frog, while it was located distal to the inner plexiform layer in the chick and cat. These results support the Muller cell K+ hypothesis and explain the polarity of SDPs. We conclude that the concept of the neutral zone is valuable for the investigation of the mechanism and polarity of transretinal field potentials. PMID- 8008250 TI - Neuronal protein GAP-43 is a member of novel group of brain acid-soluble proteins (BASPs). AB - A group of brain acid-soluble proteins (BASPs) is preliminarily characterized. In some respects BASPs are similar to high mobility group (HMG) proteins, but in contrast to HMG, all BASPs are very acidic (pI 4.4-4.6) and show abnormal mobility during SDS-PAGE electrophoresis. BASP2-1 and BASP2-2 are identified as the two forms of neuronal protein GAP-43 (B-50, pp46, F1, neuromodulin). BASP1 and BASP3 are apparently novel brain proteins. PMID- 8008249 TI - Properties of glutamate receptors are modified during long-term depression in rat cerebellar Purkinje cells. AB - Long-term depression (LTD) of synaptic transmission at parallel fiber (PF) Purkinje cell (PC) synapses occurs when these synapses are activated in conjunction with direct activation of voltage-gated calcium (Ca2+) channels of PCs. In the present study, we have used Aniracetam to test whether the expression of LTD at PF-PC synapses is due to a genuine modification of properties of alpha amino-3-hydroxy-5-methyl-isoxazole-4-propionate (AMPA) receptors of these neurons. Whole-cell recordings of PF-mediated EPSCs were performed in thin slices taken from 16-22-day-old rats. In all tested cells, bath application of Aniracetam potentiated PF-mediated EPSCs and prolonged their decay without notably changing their rising phase. On the other hand, Aniracetam prevented the induction of LTD by a pairing protocol with Ca2+ spikes and, conversely, the nootropic compound had a larger potentiating effect on PF-mediated EPSCs during expression of LTD than normally, when this change in synaptic efficacy had been induced prior to Aniracetam application. These data strongly suggest that LTD involves a desensitization of postsynaptic AMPA receptors at PF-PC synapses, or, at least, a change in their functional characteristics. PMID- 8008251 TI - Dynamic activities of the frontal association cortex in calculating and thinking. AB - We found 5-7 Hz magnetic theta waves in the frontal association cortex of adult human subjects during calculation and musical imagination by using 37-channel SQUID gradiometers. Simultaneous recording from the left and right cerebral hemispheres with two sets of 37-channel gradiometers revealed that the theta activity appeared in a waxing and waning manner in the frontal cortices of both hemispheres during the mental exercises. Electrical current dipoles for the theta waves were estimated to occur repeatedly and scatteringly in various parts of the frontal lobes of both hemispheres during continuous and intense mental exercises for 2 min. The results suggest a dynamic mode of activities in the frontal association cortex during mental effort such as calculating and thinking. PMID- 8008253 TI - Platelet-activating factor inhibits (Na+,K+) ATPase activity in rat brain. AB - In the present study, experiments were conducted to determine the effect of platelet-activating factor (PAF) on (Na+,K+)-ATPase in rat cerebral cortex. PAF, but not lysoPAF, inhibited (Na+,K+)ATPase activity, in a dose- and time-dependent manner, 10(-7) to 10(6) M being the most effective dose. These effects were abolished in the presence of PCA-4248, a PAF antagonist, indicating that the PAF effect may be mediated by its specific membrane receptors. Omission of external calcium caused an increase in the basal activity and abolished the PAF effect on (Na+,K+)ATPase. The present study demonstrates that PAF inhibits (Na+,K+)ATPase activity in the cerebral cortex and suggests that PAF released during certain pathological conditions, such as ischemia, may act on ATPase. This could be one possible mechanism of PAF action that needs further attention. PMID- 8008252 TI - Neuritic GABAergic synapses in insect neurosecretory cells. AB - The localization of synaptic gamma-aminobutyric acid (GABA) receptors on cockroach dorsal unpaired median (DUM) neurons of the last abdominal ganglion was investigated. These neurosecretory cells, mainly octopaminergic, possess a soma located on the dorsal midline of the ganglion, from which emerges a short primary neurite dividing into two symmetrical lateral branches on both lateral edges of the ganglion. GABA pressure ejections onto the soma and onto the neuritic arborization elicited hyperpolarizations. Moreover, electrical stimulation of the anterior connectives evoked a postsynaptic potential, mainly inhibitory. This response and the GABA hyperpolarization of the neuritic field are antagonized by lateral application of picrotoxin while soma GABA hyperpolarization remained unchanged. This suggests that there are two kinds of GABA receptors located (i) onto the soma membrane of the DUM neurons and called extrasynaptic receptors, (ii) on the neuritic arborization, called synaptic receptors and implicated in the connection between neurons coming from the anterior part of the nervous system and the DUM cells. Immunohistological double staining technique reinforced the electrophysiological results by showing the presence of GABA-like immunoreactive processes next to octopamine-like immunoreactive ones. PMID- 8008254 TI - Climbing fiber responses in cerebellar vermal Purkinje cells during perturbed locomotion in decerebrate cats. AB - We recorded spike potentials from Purkinje cells in the lateral vermis of lobule V in cat cerebellum, and found significant enhancement in climbing fiber discharges during perturbed locomotion. Five adult cats were decerebrated at a precollicular level, and 4-5 days thereafter, they were mounted on a treadmill. During stable locomotion at 36 cm/s belt velocity, climbing fiber responses were slightly modulated with a weak increment at the swing phase of the ipsilateral forelimb. When the left contralateral forelimb alone was suddenly imposed with a faster belt velocity of 61 cm/s, the occurrence of the climbing fiber discharges was significantly enhanced during the late swing phase of the ipsilateral forelimb. This observation is in accordance with the general notion that climbing fiber responses represent error signals in control of movements. PMID- 8008255 TI - Benefits of health promotion in occupational health. PMID- 8008256 TI - Rational assisted suicide: where do you stand? What do you tell your patients? AB - As people live longer they fear being victimized by medical technology. Rational suicide has emerged as an alternative to prolonged, dependent, possibly painful life. Primary health care providers must be prepared to provide their patients with compassionate, clear, and useful information. PMID- 8008257 TI - Age-specific well child charting forms. PMID- 8008258 TI - Are we practicing what we preach? PMID- 8008259 TI - NPs must not be complacent about health care reform. PMID- 8008260 TI - Culturally sensitive breast cancer screening programs for older black women. AB - Breast cancer is the leading cause of cancer mortality among black women. Elderly black women are particularly vulnerable and suffer the "double jeopardy" effect of older age and minority status. Older black women are not benefiting from the early detection provided through breast cancer screening. Factors that prevent this population from using breast cancer screening include cost, accessibility, availability, lack of knowledge, health care provider variables, and lack of community involvement. Breast cancer screening programs are needed that address cultural diversity to screen women who presently are not seen according to established guidelines. This article focuses on the need for primary care providers to offer culturally sensitive breast cancer screening programs designed for the older black woman. A model is presented based on Leininger's Culture Care Theory and the Health Belief Model. Specific strategies to increase the older black woman's participation in breast cancer screening practices are described. PMID- 8008261 TI - Diagnosis and treatment of ankle sprains. AB - Clinicians in ambulatory and primary care are almost guaranteed, at some point in their practice, to encounter a patient who has suffered an ankle injury. They must be prepared to diagnose, treat, and refer appropriately. By understanding the anatomy of the ankle, the health care provider will understand the mechanisms and common types of injury. By using techniques of inspection, palpation, and performing the anterior drawer and talar tilt tests, the clinician can grade a sprain accordingly, and refer for x-rays or orthopedic consultation appropriately. The principles of RICE (rest, ice, compression, elevation) are explained and different treatment methodologies for grades I to III of sprain are discussed. PMID- 8008262 TI - Insulin measurement and preparation among diabetic patients at a county hospital. AB - The investigator conducted a pilot study of 52 insulin-using adult diabetic patients at an urban county hospital in the Southeast. The purpose was to assess the ability of adult diabetic patients to measure and prepare insulin in a syringe. Results indicated that patients exhibited important deficits in their ability to prepare and measure insulin in a syringe. In addition, many subjects had difficulty with basic arithmetic involving addition and were unable to calculate their total amount of regular and long-acting (NPH) insulin. Other interesting findings were: 1) 48% did not roll the NPH vial to mix it properly, 2) 71% of the sample population did not eliminate air bubbles from the syringe, and 3) 23% of the sample population contaminated the regular insulin with the NPH insulin. Factors found to be associated with patients' insulin preparation tasks were age, arthritis of the hands, visual acuity, and education. PMID- 8008263 TI - Developing a collaborative practice agreement for the primary care setting. AB - One of the goals of joint or collaborative practice is to improve health care services. With quality assurance and quality improvement being integral parts of modern-day health care, nurse practitioners need a mechanism to define the standards by which they practice. Collaborative practice agreements document the nurse practitioner's scope of practice and educate physicians, administrators, managers, and legal counsel. The outline presented in this article guides primary care practitioners through the document construction and approval process. PMID- 8008264 TI - Nedocromil: a new anti-inflammatory drug for asthma. PMID- 8008265 TI - Documenting advance directives. PMID- 8008266 TI - Auscultating bowel sounds. PMID- 8008267 TI - What to do if you've been exposed to T.B. PMID- 8008268 TI - Looking at creatinine levels. PMID- 8008270 TI - Communicating without words. PMID- 8008269 TI - Injured on the job? PMID- 8008271 TI - Caring for patients with prostate cancer. PMID- 8008272 TI - Reducing violence at work. PMID- 8008273 TI - After thrombolytic therapy: avoiding a disabling complication. PMID- 8008274 TI - Why wouldn't Mr. Morton leave? PMID- 8008275 TI - Identifying sinus arrest and exit block. PMID- 8008276 TI - Treating diphenhydramine overdose. PMID- 8008278 TI - No negative attitudes allowed. PMID- 8008277 TI - Stroke care--piecing together the long-term picture. PMID- 8008279 TI - Opening your eyes to intraocular drug administration. PMID- 8008280 TI - What Mr. Connor couldn't say. PMID- 8008281 TI - Postoperative pain. Getting a grip on the facts. PMID- 8008283 TI - How to identify electrolyte imbalances on your patient's E.C.G. PMID- 8008282 TI - Pain control--keeping current. PMID- 8008284 TI - What to do after a med error. PMID- 8008285 TI - After the loss--offering families something more. PMID- 8008286 TI - Documentation tips to help you stay out of court. PMID- 8008287 TI - Myths & facts about diabetic hypoglycemia. PMID- 8008288 TI - Guide to travel nursing. PMID- 8008289 TI - Keying in on the new N.C.L.E.X. test. PMID- 8008290 TI - My mother, my patient. PMID- 8008291 TI - Taking accurate measure. PMID- 8008292 TI - It's time to take another look at New York's confidentiality law. PMID- 8008293 TI - Restrictive covenants: how restrictive? PMID- 8008294 TI - Thomas O. Sweet. A credit to himself and his profession. PMID- 8008295 TI - Alternative method for removing gutta-percha from canals. AB - A simple method of removing gutta-percha from root canals has been presented. This method is less time consuming, and may reduce some of the complications that result from endodontic retreatment. PMID- 8008296 TI - Innovations in Class II orthodontic correction. AB - Recent advances in metallurgy have led to the introduction of new techniques that allow the upper molars to be distalized. Class II molar correction is achieved in a few months without relying on patient cooperation. PMID- 8008297 TI - Mahlon Loomis, D.D.S. Inventor of wireless telegraphy. AB - Before Guglielmo Marconi was even born, Mahlon Loomis was harnessing electricity from the atmosphere. Sadly, this dentist from upstate New York has not received the credit he deserves. PMID- 8008298 TI - New York University Dental Center Library. Preparing to meet the information needs of the dental team today and in the 21st century. AB - The introduction of new computer technology has been changing the way libraries provide access to the vast amount of information being produced in the fields of medicine and dentistry. The NYU Dental Library is responding to the challenge with new systems that improve its daily operation and expand users' abilities to gain access to the data they need. PMID- 8008299 TI - Whither health care reform? PMID- 8008301 TI - The changing pattern of multiple births in the United States: maternal and infant characteristics, 1973 and 1990. AB - OBJECTIVE: To evaluate changes in the incidence and proportion of live births by plurality in the United States between 1960 and 1990, and to compare the distribution of singleton, twin, and triplet and higher-order births (triplet+) by maternal and infant characteristics for 1973 and 1990. METHODS: Vital statistics data were used to conduct a population-based analysis of all live births from 1960-1990 and to compare changes in the incidence and outcomes of live births between 1973 and 1990 by maternal and infant characteristics. RESULTS: Between 1960 and 1973, the number of twin births paralleled that of singletons, whereas the number of triplet+ births remained fairly constant. Between 1973 and 1990, twin births increased at twice the rate of singletons (65 versus 32%), and triplet+ births increased at seven times the rate of singletons (221 versus 32%). The resulting frequencies of occurrence changed from one in 55 to one in 43 births for twins and from one in 3323 to one in 1341 for triplet+ births. In 1990, preterm births accounted for 9.7% of singleton births, compared to 47.9% of twin births and 87.8% of triplet+ births. Because of the greater frequency of twin and triplet+ births in 1990, the observed number of very low and low birth weight infants was 24.2% greater among twin births and 142.3% greater among triplet+ births than would be expected if the 1973 ratios to singleton births had remained constant. CONCLUSION: The rise in multiple births, with the associated greater risks of prematurity and low birth weight, is of national importance. Comprehensive and aggressive prenatal care to assure the best outcomes should be the goal for clinicians caring for these women. PMID- 8008300 TI - Prognostic importance of intraoperative rupture of malignant ovarian epithelial neoplasms. AB - OBJECTIVE: To determine whether rupture of malignant ovarian epithelial tumors at the time of operation influences the patient's overall prognosis. METHODS: Between 1975 and 1990, 79 patients with stage I invasive epithelial ovarian cancer were treated at Massachusetts General Hospital. Patients were identified from the tumor registry, and charts were reviewed retrospectively. In 71 of the 79 cases, pathologic slides were evaluated. Of the 79 patients, 36 had stage Ia tumors, 20 stage Ic secondary to intraoperative rupture (Ic-rupture), and 17 stage Ic secondary to capsular invasion-serosal disease or positive ascites or washings (stage Ic-other). Survival analysis was performed to compare the three groups of patients. RESULTS: There were four recurrences and deaths among the 20 women with stage Ic-rupture tumors (20%), compared to one (3%) among the 36 women with stage Ia. The recurrence-free survival at the median follow-up time for the two groups was 97 +/- 3 and 78 +/- 10 months, respectively (P = .03); overall survival was 97 +/- 3 and 73 +/- 12 months (P = .04). There were two recurrences (12%) and one death (6%) among the 17 women with stage Ic-other, giving recurrence-free and overall survivals of 88 +/- 8 and 94 +/- 6 months, respectively. The survival experience of this last group was not significantly different from that in the Ic-rupture group (P = .2). The hazard ratios for overall survival associated with stage Ic-rupture and each potential confounder, except for bloating, exceeded 6.5, with P < or = .10. All deaths occurred in the 28 patients with grade 2 or 3 tumors. Even in this smaller group, the hazard ratio for stage Ic-rupture was 6.8 (P = .09). CONCLUSION: Intraoperative rupture of malignant epithelial ovarian neoplasms may worsen the prognosis of patients with stage I ovarian cancer. PMID- 8008302 TI - Outcome of twin pregnancies complicated by a single intrauterine death: a comparison with viable twin pregnancies. AB - OBJECTIVE: To examine the perinatal and maternal outcomes in twin pregnancies when a single intrauterine death occurs. METHODS: This was a retrospective, observational study. Comparison was made to viable twin pregnancies. RESULTS: Of a total 34,804 live deliveries, 342 were documented as twin births at a gestation of greater than 20 weeks (incidence 0.98%). Of the twin pregnancies over this period, 20 (5.85%) were complicated by a single intrauterine death. There was an increase in the incidence of congenital structural abnormalities among those twins dying in utero as compared to uneventful twin pregnancies (25 versus 0.3%; P < .001). A significant proportion of these twin pregnancies had monochorionic placentas (35 versus 9%; P < .001) and were admitted to special care units (70 versus 5.6%; P < .001) as compared to the normal twin sample. Maternal morbidity has previously been described as being increased. Although there was an increased risk of nonproteinuric and mild pregnancy-induced hypertension, no adverse maternal effects of conservative management were noted in this study. CONCLUSION: The risk of a single fetal death in twin pregnancies is increased with a monochorionic placenta or a structural abnormality. Conservative management and regular surveillance seem advisable. PMID- 8008303 TI - The first-trimester growth-discordant twin: an ominous prenatal finding. AB - OBJECTIVE: To evaluate the clinical significance and the natural course of discordant twin growth found during the first trimester of pregnancy. METHODS: This was a retrospective survey between 1992-1993 of women presenting to the ultrasonographic unit with twin pregnancies in which considerable interfetal size variation was noted in the first trimester. Discordant embryonal growth was defined as a difference in crown-rump length corresponding to 5 or more days in the estimated gestational age. Only cases that presented with continued viability of both twins were reviewed. Cases were thoroughly followed by ultrasound examinations throughout pregnancy. Neonatal records provided the outcome data. RESULTS: Five cases with first-trimester discordant twin growth were identified. All had complications of major congenital anomalies in the smaller twin, ie, diaphragmatic hernia, ventriculomegaly, schizencephaly, critical aortic atresia, and sacral agenesis. CONCLUSIONS: The first-trimester growth-discordant twin is at increased risk for congenital anomalies. Meticulous sonographic search for congenital anomalies is indicated when inter-twin size variation is evident in the first trimester. PMID- 8008304 TI - Meconium-stained amniotic fluid: increased risk for adverse neonatal outcome. AB - OBJECTIVE: To determine the risk of adverse neonatal outcome associated with meconium-stained amniotic fluid independent of that related to antepartum or intrapartum abnormalities. METHODS: A cohort of 2200 consecutive deliveries was examined and the fetal heart rate (FHR) tracings analyzed independently. Singleton term pregnancies without fatal malformations were stratified by the consistency of meconium and compared. RESULTS: Moderate or thick meconium increased the risk for adverse outcome more than threefold (relative risk 3.2, 95% confidence interval 2.0-5.2). This risk was independent of fetal heart tracing abnormalities or maternal hypertensive, kidney, or heart disease. CONCLUSION: Thick meconium alone should alert the physician to a high-risk fetal condition. This phenomenon requires continuous FHR monitoring and reassurance of fetal well-being by acid-base assessment or the equivalent, regardless of maternal disease status or the presence of abnormal FHR tracings. PMID- 8008305 TI - Serial serum CA 125 measurements for evaluation of recurrence in patients with endometrial carcinoma. AB - OBJECTIVE: To evaluate the usefulness of serum assays for CA 125 to detect recurrent endometrial carcinoma. METHODS: Two hundred sixty-six patients were studied with 1101 post-treatment assays. Patients were categorized as low, medium, or high risk based on surgical-pathologic findings. CA 125 values were analyzed with respect to each patient's disease status. RESULTS: Serial CA 125 levels were elevated (greater than 35 U/mL) in 19 of 33 patients (58%) with recurrent disease. Among 236 surgically treated patients, 97 (41.1%), 42 (17.8%), and 97 (41.1%) were considered low, medium, and high risk, respectively. None of the low-risk and only two (4.7%) of the medium-risk patients developed recurrent disease. One of the latter patients was detected based on an elevated CA 125 level alone. Twenty-seven (27.8%) of the high-risk patients developed recurrent disease, 23 of whom had elevated pre-treatment CA 125. Fifteen of 16 (94%) with recurrent disease had an elevated CA 125 level. Nine of 12 patients with papillary serous carcinoma experienced recurrence; eight of these nine had elevated CA 125 levels at diagnosis and recurrence, in contrast to only one patient with a normal pre-treatment level (P = .018). False elevations were noted in 13 patients, 12 of whom had received radiation therapy. CONCLUSIONS: CA 125, if elevated at diagnosis of endometrial carcinoma, is an important marker for recurrent disease. The use of serial CA 125 assays is most beneficial in diagnosing recurrence in a high-risk population, including patients with papillary serous carcinomas. False elevations may occur following radiation therapy. PMID- 8008306 TI - Modulation of human granulosa cell steroid production in vitro by tumor necrosis factor alpha: implications of white blood cells in culture. AB - OBJECTIVE: To test the hypothesis that the macrophage cytokine, tumor necrosis factor-alpha (TNF-alpha), directly inhibits progesterone, estrone (E1), and estradiol (E2) synthesis by human granulosa cells in vitro in the presence and absence of white blood cells. METHODS: Granulosa cells from follicle aspirates of patients undergoing in vitro fertilization (IVF) were separated from red blood cells on 50% Percoll columns. Such preparations contained numerous white blood cells (lymphocytes, 40-52%, and macrophages, 6-14%) as determined with immunocytochemistry. In some studies, anti-CD45 magnetic beads followed by an additional adherence step and media change were used to remove white blood cells from granulosa cell cultures. Granulosa cells with and without associated white blood cells were cultured in basal and hCG-supplemented media. Androstenedione (40 ng/mL) and/or recombinant TNF-alpha (0.5-50 ng/mL) were added to triplicate wells. Media were harvested for radioimmunoassay of progesterone, E1, and E2 after 24 and 48 hours of incubation. RESULTS: The effects of TNF-alpha on progesterone production in white blood cell-associated cultures were inconsistent when 0.5 ng/mL TNF-alpha was added under basal conditions. At higher TNF-alpha doses (5-50 ng/mL) and under hCG-stimulated conditions, there was a consistent decrease in progesterone production, but the effect was not clearly dose dependent. It was possible to remove white blood cells effectively from granulosa cell cultures. In granulosa cell cultures without associated white blood cells, 0.5 ng/mL of TNF-alpha at 48 hours produced an increase in progesterone, whereas 50 ng/mL of TNF-alpha decreased progesterone (P < .001). Estrone and E2 were both decreased by TNF-alpha regardless of whether white blood cells were present in culture, without clear evidence of dose-dependency. Granulosa cell viability and proliferation were unaffected by TNF-alpha as demonstrated by direct cell counts, trypan blue exclusion, and tetrazolium salt viability assays. CONCLUSIONS: In the normal ovary, TNF-alpha may influence the development of the dominant follicle by inhibiting aromatase activity. It may also mediate oocyte maturation disorders and ovarian endocrine dysfunction in some pathologic states. White blood cells can be effectively removed from granulosa cell cultures. Application of this removal technique will facilitate future granulosa cell studies by allowing more precise determination of direct granulosa cell function. PMID- 8008307 TI - Cervical cone margins as a predictor for residual dysplasia in post-cone hysterectomy specimens. AB - OBJECTIVE: To determine the relation between dysplasia at cervical cone margins and the presence or absence of residual dysplasia in post-cone hysterectomy specimens. METHODS: We performed a 6-year retrospective, multicenter study and reviewed 250 cases in which the patient had a cold-knife cervical cone biopsy followed by a hysterectomy within 6 months. Pathology reports from 23 institutions described the margins in conization specimens and the subsequent status of residual dysplasia in the hysterectomy specimens. RESULTS: There was a statistically significant difference in the prevalence of residual dysplasia in hysterectomy specimens between patients with positive margins on cone biopsy (47%) and those with negative margins (23%) (P < .01). The positive predictive value for residual dysplasia given positive cone margins was 47%, and the negative predictive value was 77%. The grade of post-cone residual dysplasia increased commensurately with the grade of dysplasia in the conization specimen. CONCLUSIONS: The presence of dysplasia at the cervical cone margin relates significantly with the presence of residual dysplasia in the post-cone hysterectomy specimen. The grade of residual dysplasia in the post-cone hysterectomy specimen increased as the grade of dysplasia in the conization specimen increased. Free margins on a cone biopsy specimen with dysplasia offer reassurance that invasive cancer is not present in the remaining uterus. PMID- 8008308 TI - Bed rest in pregnancy. AB - OBJECTIVE: To summarize existing data about the effectiveness of bed rest when used to improve various pregnancy outcomes and to determine how often bed rest is used and the cost associated with its use. DATA SOURCES: We used the MEDLINE data base to search for all English language papers evaluating the effectiveness of bed rest in pregnancy. We also reviewed a number of textbooks and the 1988 National Infant Mortality Survey. METHODS OF STUDY SELECTION: We reviewed these sources for recommendations about using bed rest in various obstetric conditions. We used the 1988 National Infant Mortality Survey to determine how often bed rest was used either to prevent or to treat various obstetric conditions and estimated the costs associated with its use. DATA EXTRACTION AND SYNTHESIS: Bed rest is used in nearly 20% of all pregnancies to prevent or treat a wide variety of conditions, including spontaneous abortion, preterm labor, fetal growth retardation, edema, chronic hypertension, and preeclampsia. There is little evidence of effectiveness. The estimated costs associated with bed rest, including hospitalization, lost wages, and lost domestic productivity, range from more than $250 million to billions of dollars per year. CONCLUSIONS: Bed rest is used extensively to treat a wide variety of pregnancy conditions, at substantial cost but with little proof of effectiveness. We recommend that because this intervention has failed the test of effectiveness, its use during pregnancy should be curtailed unless randomized trials demonstrate improvement in a specific outcome. PMID- 8008309 TI - The role of an electronic mail system in the educational strategies of a residency in obstetrics and gynecology. AB - Computerized electronic mail (E-mail) systems provide a rapid means of data sharing and are used in a variety of commercial and industrial settings for the widespread distribution of memoranda. We adapted an E-mail system to our program to determine the feasibility of incorporating such a system into didactic resident education in obstetrics and gynecology and to assess resident response to this form of computer-based learning. The system was programmed to distribute one review question per day to 24 resident physicians for 60 days. Residents were given 24 hours to respond and comment. Each question was discussed and appropriate references distributed within 48 hours of presentation. All questions and responses were then stored in an electronic file folder for later review. An examination was given at completion of the project (post-test), and these scores were compared to performance during the project (pre-test). An anonymous questionnaire was distributed upon completion of the project to assess the residents' overall satisfaction with the program. The system was well received by the residents. On a scale of 1 to 6 (1 = lowest; 6 = highest), resident satisfaction was high, with an overall average rating of 5.0. Using this scale, residents assessed their frustration level as 1.5. Average daily participation was 85%. An average of 9 minutes was required to complete each question and review prior responses and discussion; this interval was not significantly different among the postgraduate years. Scores on the examination at project completion were significantly higher than performance during the project.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8008310 TI - The case-control study: a primer for the obstetrician-gynecologist. AB - Case-control studies begin at the end. Two groups of patients, those with disease (cases) and those without (controls), are compared to determine the degree of exposure to a presumed risk factor. This research method is commonly used to study rare diseases or diseases that take years to develop. If a higher proportion of cases than controls has the exposure of interest, the exposure may be associated with illness. The strength of this association is measured by an "odds ratio," which is a good proxy for a relative risk when the illness in question is infrequent. Although some case-control studies are easy to do, all are easy to do poorly, especially because of selection bias in the choice of controls. A greater familiarity with the case-control study should enable obstetrician-gynecologists to evaluate critically published studies using this research method. PMID- 8008312 TI - Full-thickness Martius grafts to preserve vaginal depth as an adjunct in the repair of large obstetric fistulas. AB - We performed a modified bulbocavernosus full-thickness pedicle graft procedure on four patients with large obstetric fistulas in Ghana, West Africa. The bulbocavernosus fat pad was harvested in the usual manner, and the full-thickness skin patch was taken from the medial thigh. All grafts showed 100% take by the tenth postoperative day. Adequate vaginal depth and caliber were obtained in all patients. Sexual function resumed in all patients except one, who suffered a recurrent vesicovaginal fistula. This method of vaginoplasty may be useful in patients who have massive vaginal-wall destruction of either gynecologic or obstetric origin. PMID- 8008311 TI - Intrapartum bimanual tocolytic-assisted reversal of face presentation: preliminary report. AB - OBJECTIVE: To design and conduct a mode of vaginal delivery for mentoposterior presenting fetuses when cesarean delivery is not possible. METHODS: Eleven orthodox Jewish parturients who refused cesarean delivery had intrapartum bimanual conversion of mentoposterior to occipitoanterior presentation, concomitant with ritodrine infusion in ten. RESULTS: Excluding the first case, in which ritodrine was not administered, the maneuver was successful and vaginal delivery was achieved. CONCLUSION: This maneuver, performed with intravenous ritodrine tocolysis, might be an alternative mode of delivery in the presence of mentoposterior presentation when cesarean delivery is not possible. More experience is needed with this technique before it is performed routinely. PMID- 8008313 TI - Electroconization of the cervix with a fine-needle electrode. AB - OBJECTIVE: To obtain electroexcised specimens in which the endocervical margin of the lesional tissue is devoid of thermocoagulation injury, facilitating accurate histologic interpretation of early stromal invasion. METHODS: Using local anesthesia, we performed electroexcision with fine-needle electrodes and a tonsillar snare wire; no sutures to the lateral vessels were required. We tried to obtain cylindrical specimens. The procedure was performed in 38 women with deep canal involvement by squamous intraepithelial lesions, without colposcopically visible endocervical margins. RESULTS: The mean duration of the procedure was 12 minutes (range 8-26). Complications occurred in seven of 38 patients (18%): four cases of perioperative bleeding, one of delayed bleeding, and two of asymptomatic stenosis of the external os. All cases were managed on an outpatient basis. Two cases of unsuspected microinvasive carcinoma were discovered. CONCLUSION: In nonpregnant women in whom the endocervical limit of a lesion cannot be visualized with a colposcope, fine-needle electroconization is an attractive alternative to loop electroexcision. With this technique, cervical specimens can be collected without thermal damage to the endocervical margins. PMID- 8008314 TI - Transvaginal ultrasonographic diagnosis of bladder-wall invasion in patients with cervical cancer. PMID- 8008315 TI - Risk factors for severe preeclampsia. PMID- 8008316 TI - Pseudomyxoma peritonei: a review of 23 cases. AB - OBJECTIVE: To review the experience at the Massachusetts General and Brigham and Women's Hospitals with 23 women treated for pseudomyxoma peritonei between 1961 and 1991. METHODS: Patients were identified retrospectively from the tumor registry at the Massachusetts General and Brigham and Women's Hospitals, and all charts were reviewed. The median follow-up interval was 2.5 years (range 3 months to 31 years). RESULTS: The mean age at diagnosis was 58 years (range 26-76). Pseudomyxoma peritonei was found in association with ten (44%) ovarian tumors of borderline malignancy, nine (39%) ovarian cystadenocarcinomas, and four (17%) appendiceal cystadenocarcinomas. Three patients had synchronous tumors in the ovary and appendix. All patients underwent surgical staging and cytoreduction. Eleven patients received postoperative therapy and, of these, nine developed a recurrence; 12 patients received no further therapy and, of these, three developed a recurrence. However, these groups were not pathologically comparable. With respect to survival, of the ten patients with borderline malignancies, seven had no evidence of disease, one was alive with disease, and two died of disease. For the nine patients with ovarian cystadenocarcinomas, three had no evidence of disease, one was alive with disease, and five died of disease (median time to death 18 months). For the four patients with appendiceal carcinomas, two had no disease, one was alive with disease, and one died with disease. Among all 23 patients, 12 (52%) developed a recurrence, with a range of time to first recurrence of 3 months to 19 years. Eight women required at least one additional laparotomy because of accumulation of gelatinous material. CONCLUSIONS: Although pseudomyxoma peritonei is associated with borderline and well-differentiated tumors, recurrence is common and the prognosis after recurrence is guarded. Involvement of the appendix is common; therefore, appendectomy is indicated when pseudomyxoma is encountered. To date, surgery has been the only effective therapy for this disease, and adjuvant therapy has not been shown conclusively to be of benefit. PMID- 8008318 TI - Risk factors for menopausal hot flashes. AB - OBJECTIVE: To find predictors of hot flashes at natural menopause. METHODS: A cross-sectional sample of 334 black and white, naturally menopausal women was selected from a control group in a population-based study of reproductive cancers in central North Carolina. Women reported whether they had experienced hot flashes at the time of menopause. Life-style factors and reproductive histories of those with and without hot flashes were compared. RESULTS: Compared to women who were older at menopause, those reporting natural menopause before age 52 years had a significantly increased probability of having hot flashes (prevalence ratio 1.5, P = .04). Less than a high school education was significantly related to an increased probability of hot flashes (prevalence ratio 1.4, P = .20). There was significant interaction between cigarette smoking and body mass index (BMI), so that thin women who smoked in the premenopausal period were most likely to experience hot flashes (prevalence ratio 1.9, P = .03). Among non-smokers, BMI appeared to have no effect on the probability of hot flashes. Alcohol use, although not statistically significant, suggested a positive relation with hot flashes over and above that incurred from smoking. In addition, menarche before the age of 12 (prevalence ratio 0.6, P = .08) and a history of irregular menstrual cycles (prevalence ratio 0.6, P = .08) were marginally related to a decreased prevalence of hot flashes. Race, parity, and age at first and last pregnancy had no relation to hot flashes. CONCLUSION: Socioeconomic factors and those related to the decline of estrogen production are related to the occurrence of hot flashes at the time of menopause. PMID- 8008317 TI - Mature cystic teratoma: a clinicopathologic evaluation of 517 cases and review of the literature. AB - OBJECTIVE: To evaluate the clinical and pathologic presentation of mature cystic teratomas and the trends in management over a 14-year study period. METHODS: Tumor registry data and medical records between January 1, 1975 and December 31, 1989 were analyzed with respect to patient age, tumor size, bilaterality, malignant transformation, and treatment. RESULTS: Five hundred seventy-three tumors were removed from 517 patients. The median and mean (+/- standard deviation) age was found to be 30 and 32 +/- 11.3 years, respectively. Three hundred ten (60%) of the patients were asymptomatic. The mean tumor size was 6.4 +/- 3.5 cm. The bilaterality rate was 10.8%. The rate of torsion was 3.5%; larger tumors underwent torsion more frequently than smaller tumors (P = .029). The rate of malignant transformation was 0.17%. The mean cyst diameter for patients undergoing cystectomy was 5.7 +/- 2.4 cm; for oophorectomy, 8.0 +/- 4.1 cm; and for hysterectomy, 6.1 +/- 3.8 cm. Oophorectomies were performed for larger tumors when compared to cystectomies (P = .01). The number of hysterectomies was stable throughout the study period, whereas the number of oophorectomies decreased and the number of cystectomies increased markedly. Contralateral ovarian biopsy was common (48.5%) early in the study period. By 1989, the biopsy rate was less than 1%. CONCLUSIONS: We found the prevalence rates of symptomatic tumors, torsion, and malignant degeneration to be less than those previously reported by most other investigators. In addition, there has been an important change over the past 14 years in the management of these neoplasms, with an increased tendency for ovarian preservation, as evidenced by the more frequent use of cystectomy and a decrease in contralateral ovarian biopsy. PMID- 8008320 TI - Cervical sonography in preterm labor. AB - OBJECTIVE: To improve the accuracy of the diagnosis of preterm labor by comparing transvaginal sonography to digital examination of the cervix. METHODS: We performed transvaginal sonography in women with preterm labor who had completed a course of parenteral tocolysis. Cervical length was measured according to criteria reported previously. Cervical sonographic findings were not used in diagnosis or management. Sonographic cervical length was compared to digital assessment of dilation and effacement to assess the risk of preterm birth after treatment for preterm labor. RESULTS: Forty-eight singleton and 12 twin gestations were studied. Thirty women were nulliparous and 30 were parous. The mean (+/- standard deviation) gestational age was 31.1 +/- 2.7 weeks (range 24 35) at the examination and 35.6 +/- 2.9 weeks (range 26-43) at delivery. Twenty four subjects delivered before 36 weeks' gestation and 36 delivered at or after 36 weeks. Cervical sonography was distinctly superior to digital assessment of dilation and effacement as a test for delivery before 36 weeks, when compared using receiver operating characteristic curves. This analysis indicated a cervical length of 30 mm as the best cutoff to maximize sensitivity and specificity. All 24 subjects who delivered preterm had cervical lengths less than 30 mm. Cervical sonography was especially useful in selecting women with preterm labor who would not deliver prematurely, ie, a high negative predictive value. None of 15 women whose cervical length was 30 mm or more delivered spontaneously before 36 weeks. CONCLUSION. Among women treated for preterm labor, a cervical length of at least 30 mm predicted a low likelihood of preterm birth. Cervical sonography may improve the accuracy of diagnosis in women treated for preterm labor. PMID- 8008319 TI - Antenatal hospitalization among enlisted servicewomen, 1987-1990. AB - OBJECTIVE: To describe the prevalence of, and indications for, antenatal hospitalization among women who delivered live and stillborn infants. METHODS: We reviewed the records of a cohort of 1825 black and white enlisted women who delivered from 1987-1990 at the four largest Army medical centers in the United States. Women with multiple gestations and those whose pregnancies ended before 20 weeks' gestation were excluded. Records of all women with preterm deliveries and a one-third sample of women with term deliveries were abstracted. RESULTS: Overall, 26.8 +/- 1.6% (mean +/- standard error) of the women were hospitalized antenatally. Of the estimated 702 antenatal hospitalizations, 44.0 +/- 3.4% were related to preterm labor, 10.3 +/- 1.9% to preeclampsia, 5.5 +/- 1.5% to hyperemesis, and 4.7 +/- 1.5% to urinary tract or kidney infection. The prevalence of hospitalization was lowest before 20 weeks (5.0 +/- 0.8%) and highest at 33-36 weeks (12.2 +/- 1.2%). Small and probably clinically insignificant differences between black and white women were noted in the overall prevalence of antenatal hospitalization and in the indications for hospitalization. CONCLUSION: As measured by hospitalization, severe antenatal morbidity is common in this population of healthy enlisted women. PMID- 8008321 TI - Short labor: characteristics and outcome. AB - OBJECTIVE: To determine the characteristics and consequences of short labor. METHODS: Ninety-nine term pregnancies with singleton vertex presentation and labor lasting 3 hours or less were compared with controls with longer labor, matched to the index cases by maternal age, parity, and birth weight. RESULTS: Short labor occurred mostly in multiparas. Both the first and second stages of labor were found to be shortened in these cases. There was significantly more placental abruption, uterine tachysystole, and maternal cocaine use among short labor cases. Major perineal lacerations, postpartum hemorrhage, birth trauma, and low Apgar scores were distributed approximately equally between cases and controls. A preponderance of the bad outcomes in the short labors occurred in the subgroup of those with rates of dilatation and descent that exceeded established 95th percentile limits. CONCLUSIONS: Labors of 3 hours or less in duration were strongly associated with placental abruption, but were otherwise not major contributors to maternal and fetal morbidity. PMID- 8008322 TI - Modification of an intrauterine shunt catheter to reduce the incidence of spontaneous displacement. AB - OBJECTIVE: To determine which of four types of catheters would be the least likely to become displaced spontaneously when employed as a fetoamniotic shunt, by testing the force required to remove the catheters from a lamb's bladder. METHODS: The catheter designs tested were unfeathered straight, unfeathered pig tailed, superficially feathered, and deeply feathered. The catheters were placed percutaneously into the urinary bladders of recently euthanized newborn lambs. The force required to withdraw the catheters was determined, employing nine measurements for each catheter design. RESULTS: The mean force required to remove the straight catheter was 12 g (95% confidence interval [CI] 2-21 g), the pig tailed catheter 22 g (95% CI 13-32 g), and the superficially feathered catheter 149 g (95% CI 139-160 g). Extracting the deeply feathered catheter consistently required a force greater than 300 g, which was the upper limit of detection for our instruments. CONCLUSION: Feathering the catheter increases the force required to extract it from a fetal viscus. We believe that use of feathered catheters will significantly reduce the incidence of unwanted spontaneous displacement. PMID- 8008323 TI - Placenta previa and prior cesarean delivery: how strong is the association? AB - OBJECTIVE: To investigate the occurrence of placenta previa following a cesarean delivery. METHODS: We conducted a case-control study using 1984-1987 Washington state birth certificate data. Analysis was restricted to women who reported one or more previous live births. The study population included 490 women with a pregnancy complicated by placenta previa and 1477 randomly selected controls. Unconditional logistic regression was used for statistical analysis. RESULTS: After adjustment for confounding factors, the odds ratio for placenta previa in association with one or more previous cesarean deliveries was 1.48 (95% confidence interval 1.13-1.95). CONCLUSIONS: Women with a history of cesarean delivery are 50% more likely to have a subsequent birth complicated by placenta previa than those without such a history. This magnitude of excess risk is lower than the relative risks reported in previous studies. PMID- 8008324 TI - The effect of placenta previa on blood loss in second-trimester pregnancy termination. AB - OBJECTIVE: To determine whether placenta previa increases bleeding during second trimester pregnancy termination. METHODS: The records of 131 consecutive women undergoing elective pregnancy termination at 13-24 weeks' gestation were reviewed and divided into those with and without placenta previa based on an ultrasound examination before the procedure. These two groups were then compared for differences in maternal characteristics, estimated blood loss, operative time, infection, and hospital admission. RESULTS: Twenty-three of 131 women (17.6%) had placenta previa. Sixty-seven percent of the previa patients smoked, versus 37% in the control group, a statistically significant difference. A statistical difference was noted with respect to placenta previa in intraoperative blood loss (P < .05), but not operative time, time to discharge, infection, hemorrhage, or other complications. CONCLUSION: Second-trimester pregnancy terminations in the presence of placenta previa are associated with a higher estimated blood loss, but no apparent increase in abortion-related infection, postoperative transfusion requirements, hysterectomy, or other complications. PMID- 8008325 TI - Azithromycin and erythromycin in the treatment of cervical chlamydial infection during pregnancy. AB - OBJECTIVE: To compare azithromycin and erythromycin in regard to side effects, intolerance, and cure rate in a pregnant population with chlamydial cervicitis. METHODS: Thirty women were randomized to receive either erythromycin, 500 mg orally four times a day for 7 days, or azithromycin, 1 g orally as one dose. All subjects completed questionnaires identifying the incidence of nausea, vomiting, diarrhea, abdominal pain, and anorexia. Post-treatment cultures were taken from all subjects. RESULTS: All subjects receiving erythromycin reported two or more gastrointestinal side effects, versus none in the azithromycin group (P < .001). Five of 15 subjects in the erythromycin treatment arm were intolerant to the 500 mg dose given four times a day, compared to none in the azithromycin group (P < .025), so the dosage was lowered to 250 mg four times a day to complete the course. Repeat cervical testing demonstrated similar cure rates for both medications: 100 and 93% (14 of 15) for azithromycin and erythromycin, respectively. CONCLUSION: These data suggest that azithromycin is a valid treatment option in pregnant patients who cannot tolerate erythromycin because of side effects. PMID- 8008326 TI - Hourly fetal urine production rate in the fasting and the postprandial state of normal and diabetic pregnant women. AB - OBJECTIVE: To examine whether maternal meal ingestion affects fetal urine production in normal and diabetic pregnancies and whether fetal urine production is increased in diabetic pregnancy. METHODS: The hourly fetal urine production rate was measured before and after breakfast in 17 fetuses of diabetic mothers and 14 of women with normal glucose tolerance. The rate was calculated by taking serial measurements of fetal bladder volume at 2-3-minute intervals by ultrasonography. RESULTS: In the control group, the hourly fetal urine production rate was significantly greater during the 2 hours after breakfast than that in the fasting state (P < .0005). In the diabetic group, the rate also tended to increase after breakfast (P = .07). In the postprandial state, the hourly fetal urine production rate was not significantly different between the groups. However, in the fasting state, it was significantly greater in the diabetic group than in the control group (P < .03). CONCLUSIONS: Maternal meal ingestion should increase fetal urine production. The increased fetal urine production in the fasting state in diabetics is assumed to be one cause of hydramnios. PMID- 8008327 TI - First-trimester diagnosis of fetal congenital heart disease by transvaginal ultrasonography. AB - OBJECTIVE: To describe the feasibility of diagnosing fetal congenital heart defects by transvaginal ultrasonography during the first trimester of pregnancy. METHODS: Pregnant women presenting to the Ultrasonographic Unit at the Chaim Sheba Medical Center who had a diagnosis of fetal heart defects were reviewed retrospectively. Attention was paid to prenatal ultrasound studies, karyotype, and pathologic examinations. RESULTS: Using high-resolution transvaginal ultrasonography, we were able to detect fetal tachycardia (one case), ectopia cordis with ventricular septal defect (one case), atrioventricular septal defect (two cases), ventricular septal defect with persistent truncus arteriosus (one case), tetralogy of Fallot (two cases), and large right atrium with unguarded tricuspid valve (Uhl disease) (one case). Seven of these fetuses had normal karyotypes and all showed additional sonographic abnormalities, including septated cystic hygroma (three cases), hydrops (ascites and pericardial effusions) (two cases), omphalocele (one case), and bilateral agenesis of kidneys (one case). Only one fetus with an abnormal karyotype (45,XO) showed a combination of septated cystic hygroma with hydrops. CONCLUSIONS: High-resolution duplex Doppler transvaginal ultrasonography during the first trimester of pregnancy seems to be a useful diagnostic method for detecting some congenital heart diseases. PMID- 8008328 TI - Detection of cleft lip by early second-trimester transvaginal sonography. AB - OBJECTIVE: To describe the detection of cleft lip in the early second trimester using transvaginal sonography. METHODS: We analyzed retrospectively 14,988 ultrasound examinations conducted for fetal malformations between 12-16 weeks' gestation. Seventy-five percent of the patients were at low risk for fetal anomalies and 25% were at high risk. RESULTS: Eleven cases of fetal cleft lip with or without cleft palate were detected by transvaginal sonography among 14,988 fetuses (0.07%). In nine cases, no risk factors for cleft lip or palate existed. In six cases, the cleft lip represented an isolated malformation, with no other associated anomaly; in five of these six cases, the pregnancy was terminated. One additional case of a small cleft lip was not detected, for a false-negative rate of 8%. CONCLUSIONS: The fetal lips can be scanned by transvaginal sonography in the early second trimester, and fetal cleft lip can be detected in most cases. Early second-trimester detection of cleft lip by transvaginal sonography allows informed parental choice regarding continuing or terminating the affected pregnancy. PMID- 8008329 TI - Epithelial ovarian cancer: impact of surgery and chemotherapy on survival during 1977-1990. AB - OBJECTIVE: To assess the impact of surgery and chemotherapy on survival in women with epithelial ovarian cancer. METHODS: Five hundred twenty-three women were treated at the same institution in 1977-1990. All pertinent data from patient files were collected by the author. Operations were performed by senior surgeons of the hospital. Cumulative survival and survival analysis with covariates (Cox model) were calculated. Multivariate analysis was used to assess the impact of surgery and chemotherapy on survival in 244 patients who had stage III epithelial ovarian cancer. RESULTS: The overall cumulative 5-year survival for patients with epithelial ovarian cancer treated in the period 1977-1980 was significantly (P = .001) lower (33%) than that for patients treated in 1981-1985 (49%) or 1986-1990 (46%). The 5-year survival of women with stage III ovarian cancer improved from 10% in 1977-1980 to 27% in 1986-1990. In these stage III patients, chemotherapy containing cisplatin was associated with better survival than other chemotherapies, both in patients with optimal surgery (1.0- versus 2.9-fold risk of death) and in those with suboptimal surgery (1.4- versus 1.7-fold risk of death). CONCLUSIONS: The results of this study suggest that cisplatin may be more important than surgery in improving survival in stage III epithelial ovarian cancer. Thus, epithelial ovarian cancer, at least in advanced stages, is a disease not curable with aggressive surgical procedures alone. PMID- 8008330 TI - Umbilical venous erythropoietin and umbilical arterial pH in relation to morphologic placental abnormalities. AB - OBJECTIVE: To investigate the relation between the biochemical markers of umbilical venous erythropoietin and umbilical arterial pH and morphologic placental abnormalities in fetal hypoxia. METHODS: Placentas from 300 high-risk newborn infants (gestational age 24-42 weeks) were examined macroscopically and microscopically following standardized criteria. The morphologic findings were correlated with the erythropoietin concentration in umbilical venous blood and with umbilical arterial pH at birth. Venous hematocrit and circulating nucleated red blood cells were measured in 112 of these infants during the first 6 hours of life. RESULTS: The umbilical venous erythropoietin concentration correlated significantly (r = 0.74) with the number of circulating nucleated red blood cells. In 26 placentas without morphologic abnormalities, the median (and 25th and 75th percentiles) erythropoietin concentration was 35.2 mU/mL (19.2-48.7) and umbilical arterial pH was 7.30 (7.20-7.33). The erythropoietin concentration was elevated significantly when placental examination showed evidence of acute villous circulatory disturbance (61.3 mU/mL; 24.2-125.1), fetal vasculopathy (85.6 mU/mL; 23.7-119.7), or chorioamnionitis with fetal reaction (51.3 mU/mL; 27.7-118.7). The erythropoietin concentration varied significantly with the stage of placental meconium phagocytosis; it was 62.7 mU/mL (16.3-125.9) if meconium phagocytosis was classified as recent, 128.2 mU/mL (44.4-1483.2) if it was classified as a few hours old, and 66.2 mU/mL (46.3-140.1) if it was classified as a few days old. Umbilical arterial pH was not altered significantly with different morphologic placental abnormalities. CONCLUSIONS: Fetal erythropoietin production is stimulated by hypoxia after a few hours' delay and leads to increased erythropoiesis. Placental examination combined with measurement of umbilical venous erythropoietin and umbilical arterial pH provides information about earlier fetal hypoxia. PMID- 8008332 TI - Yes, there is a health care crisis. PMID- 8008331 TI - Relation of amniotic fluid C-peptide levels to neonatal body composition. AB - OBJECTIVE: To compare the correlation between fetal insulin production (as estimated by amniotic fluid [AF] C-peptide concentration) and neonatal body fat (as estimated by both anthropometrics and total body electrical conductivity) with that between fetal insulin production and birth weight or fat-free mass. METHODS: Amniotic fluid C-peptide concentration measured within 1 week of delivery was correlated with birth weight and neonatal body composition, estimated by both anthropometric measures and total body electrical conductivity within 24 hours of birth. Eighteen term neonates were studied: 13 from pregnancies complicated by diabetes and five from mothers with normal glucose tolerance. RESULTS: Six infants were large for gestational age and 12 were appropriate for gestational age. There was a significant correlation between AF C peptide level and neonatal fat mass, estimated by either anthropometric measures (r = 0.72, P = .0008) or total body electrical conductivity (r = 0.61, P = .008) methodology. The correlation was weaker between AF C-peptide level and either ponderal index (r = 0.44, P = .064) or total weight (r = 0.39, P = .11). The correlation with fat-free mass estimated by either method was not statistically significant. CONCLUSION: Our results suggest that fetal insulin production, as estimated by AF C-peptide concentration, influences fetal growth primarily through increasing fetal fat deposition rather than lean body mass. PMID- 8008334 TI - Interpreting common lab values (continuing education credit). PMID- 8008333 TI - Nurses caring for nurses: what is PAPN? PMID- 8008335 TI - Stress management for physician office nurses (continuing education credit). PMID- 8008336 TI - Health care reform. PMID- 8008337 TI - Nurses in advanced practice: culture and language are a challenge. PMID- 8008338 TI - Is someone you know chemically dependent? PMID- 8008339 TI - Infectious crystalline keratopathy due to Streptococcus pneumoniae. Possible association with serotype. AB - BACKGROUND: Infectious crystalline keratopathy is a distinctive clinical entity characterized by bacterial replication within the corena without inflammation. The authors report on a patient with infectious crystalline keratopathy due to Streptococcus pneumoniae serotype 11F. They used this isolate to study the contribution of the pneumococcal polysaccharide capsule to the pathogenesis of the infectious crystalline keratopathy. METHODS: Aliquots containing 10(6) colony forming units of pneumococci serotype 11F, serogroup 9 or 15, were inoculated into New Zealand white rabbit corneas. The corneas were examined at 24, 48, and 72 hours. Representative corneas were excised at 24 hours and processed for histopathologic analysis. RESULTS: Pauci-inflammatory crystalline lesions developed in all corneas inoculated with the serotype 11F ocular isolate by 24 hours. Suppurative keratitis developed in control corneas inoculated with serogroup 9 or 15 pneumococci. The nonocular 11F isolates produced lesions with some features compatible with infectious crystalline keratopathy. CONCLUSION: Different pneumococcal serotypes vary in their ability to produce infectious crystalline keratopathy. Because serotype differences reflect differences in the antigenic polysaccharides of the bacterial capsule, this study suggests that properties of the pneumococcal capsule may influence the initial development of infectious crystalline keratopathy. PMID- 8008340 TI - The changing spectrum of fungal keratitis in south Florida. AB - PURPOSE: To review the clinical experience with fungal keratitis in south Florida over a 10-year period. METHODS: One hundred twenty-five cases of fungal keratitis were identified in the microbiology laboratory records between January 1982 and January 1992. The medical record of each patient was reviewed. RESULTS: The most commonly associated risk factor was trauma (44%). Fungal keratitis developed in five patients using extended wear contact lenses and one patient wearing a therapeutic bandage contact lens. Clinical features included irregular, feathery margins (62%), a dry, rough texture (47%), and satellite lesions (41%). An initial positive culture was obtained in 90% of patients, with a majority of cultures becoming positive within 48 hours. The Fusarium sp accounted for 62% of the isolates, with Fusarium oxysporum being the most commonly isolated organism. New fungal isolates include Candida parapsilosis, Aspergillus terreus, Candida tropicalis, and Trichosporon beigellii. Natamycin 5% suspension was the initial antifungal agent used for 91% of the patients, with an average duration of treatment of 38 days. Twenty-five patients were treated with oral ketoconazole for a median duration of 2 weeks, in addition to topical antifungal therapy. Thirty-four patients (27%) required a penetrating keratoplasty. Six patients had recurrence of fungal keratitis after penetrating keratoplasty. CONCLUSIONS: Trauma, including contact lens wear, is the most commonly associated risk factor. The fungal organisms can be readily identified in culture. F. oxysporum is the most common organism, with new isolates identified. The mainstay of therapy is topical natamycin with the increasing use of imidazoles. PMID- 8008341 TI - Continued endothelial cell loss ten years after lens implantation. AB - PURPOSE: To investigate the effects of cataract extraction and lens implantation on the central corneal endothelium 10 years after surgery. METHODS: The authors conducted a prospective study of 253 consecutive eyes that underwent cataract extraction with or without lens implantation by one surgeon from 1976 to 1982. Three types of lens implant were used during this period. The protocol included ophthalmic examinations and specular microscopy on all eyes preoperatively, and 2 months and 1, 3, 5, and 10 years postoperatively. RESULTS: The 10-year analysis was conducted on 67 (26%) of the 253 total eyes. The remaining patients died (86 eyes [34%]), were unable to return 10 years later (93 eyes [37%]), or had secondary implants (5 eyes [2%]) or penetrating keratoplasty (2 eyes [1%]). There were no statistically significant differences among the median 10-year endothelial cell losses of 36% in 17 control cataract extractions without lens implantation (15 extracapsular and 2 intracapsular), 40% in 15 medallion iris suture implants, 32% in 28 transiridectomy clip implants, and 32% in 7 posterior chamber implants. The median exponential rate of chronic cell loss from 1 to 10 years after surgery was 2.5% per year, which did not differ significantly among the three implant groups or between the implants (2.4% per year) and controls (2.7% per year). The chronic cell loss rate was significantly higher (7.2% per year) in six eyes with cornea guttata, which was the only preoperative endothelial morphologic feature that was significantly associated with the chronic cell loss rate. CONCLUSIONS: Ten years after cataract extraction, eyes continued to lose endothelial cells from the central cornea at a rate of 2.5% per year, 2.5 to 8.0 times the rate in healthy unoperated eyes. The rate was not affected significantly by the presence of the three types of lens implants that the authors used. Postoperative eyes with cornea guttata continued to lose cells at more than twice this rate. Preoperative specular microscopy did not provide additional information helpful in predicting postoperative endothelial status or outcome. PMID- 8008343 TI - Malignant glaucoma. Clinical and ultrasound biomicroscopic features. AB - PURPOSE: To determine conditions associated with malignant glaucoma and to assess anterior segment structures in malignant glaucoma using ultrasound biomicroscopy. METHODS: Over a 3-year period, 14 eyes from 14 patients with malignant glaucoma were evaluated. RESULTS: Of the 14 eyes, 7 received medical therapy alone and 7 required both medical and surgical intervention. Predisposing factors included trabeculectomy in 12 eyes, chronic angle-closure glaucoma in 10, sudden ocular decompression in 2 (1 from suture lysis and 1 from corneal perforation), pseudoexfoliation in 4, and cessation of aqueous suppressants and cycloplegics in 2. Ultrasound biomicroscopy of two eyes showed a shallow supraciliary fluid level, anterior rotation of ciliary processes, and obstruction of the trabeculectomy osteum. CONCLUSIONS: Malignant glaucoma is associated with glaucoma surgery, chronic angle-closure glaucoma, pseudoexfoliation, sudden ocular decompression, and cessation of aqueous suppressants. On ultrasound biomicroscopy, a low supraciliary fluid level was found in two patients. PMID- 8008342 TI - 5-Fluorouracil in initial trabeculectomy. A prospective, randomized, multicenter study. AB - PURPOSE: Postoperative subconjunctival 5-fluorouracil (5-FU) injections increase the success of filtration surgery in eyes with prior filtration failure or cataract removal and in eyes with secondary glaucoma. The authors evaluate the safety and benefit of adjunctive 5-FU in eyes undergoing initial trabeculectomy. METHODS: Patients with phakic, uncontrolled, open-angle glaucoma who were undergoing initial trabeculectomy were prospectively assigned to the 5-FU group on the first postoperative day. Patients in this group received five 5-mg injections during 2 weeks after surgery. Patients in the control group received no injections. RESULTS: Preoperative intraocular pressure (IOP) and number of antiglaucoma medications were similar in the 5-FU (n = 32) and control (n = 30) groups. Transient superficial punctate keratopathy was the only postoperative complication that occurred more frequently (P < 0.05) in the 5-FU (14 eyes) than in the control eyes (3 eyes). Patients were followed for a minimum of 1 year or until a study endpoint was reached: IOP of 21 mmHg or greater with maximum medical therapy (2 5-FU eyes and 8 control eyes; P < 0.03) or cataract removal after filtration (5 treated and 3 control eyes). At last follow-up (mean, > 20 months), IOP and the number of antiglaucoma medications were significantly lower (P < 0.02) in the 5-FU eyes (IOP, 12.0 +/- 1.3 mmHg; medications, 0.2 +/- 0.1) than in the control eyes (IOP, 16.8 +/- 1.3 mmHg; medications, 0.8 +/- 0.2). Intraocular pressure was 20 mmHg or lower in 94% of 5-FU eyes and in 73% of control eyes (P < 0.03) and 16 mmHg or lower in 84% of 5-FU eyes and in 57% of control eyes (P < 0.02). CONCLUSIONS: Adjunctive 5-fluorouracil increases the rate of success, decreases the level of postoperative IOP, and reduces the need for postoperative antiglaucoma medication in eyes with open-angle glaucoma undergoing initial trabeculectomy. PMID- 8008345 TI - Reproducibility of the optic nerve head topography with a new laser tomographic scanning device. AB - BACKGROUND: Laser scanning tomography has been shown to be an accurate and reliable method for the assessment of the three-dimensional optic disc topography. The authors investigate the reliability of morphometric measurements with the Heidelberg retina tomograph, a new instrument which was designed based on this technology, which simplifies handling and is much smaller than the laser tomographic scanner. METHODS: Three independent measurements of the optic disc were performed in 39 eyes of 39 patients which were equally divided into the following three groups: glaucoma, glaucoma suspects, and controls. RESULTS: The mean coefficient of variation for measurement in the glaucoma, glaucoma suspect, and control groups was 2.9%, 5.0%, and 3.4%, respectively, for cup area; 4.9%, 4.6%, and 4.6%, respectively, for cup volume; 5.2%, 3.8% and 3.3%, respectively, for mean cup depth; and 5.2%, 4.1%, and 4.0%, respectively, for maximal cup depth. The mean standard deviation for one pixel of the total image was 30 +/- 6 microns, 28 +/- 7 microns, and 22 +/- 6 microns for the three groups, respectively. CONCLUSION: The Heidelberg retina tomograph enables fast and reliable measurement of the optic disc topography and therefore may allow exact follow-up of patients. PMID- 8008344 TI - Aqueous tube shunt to a preexisting episcleral encircling element in the treatment of complicated glaucomas. AB - PURPOSE: The treatment of glaucoma after scleral buckling surgery is often problematic. The authors investigated a series of patients in whom a silicone tube was implanted to shunt aqueous from the anterior segment to the fibrous capsule surrounding a previously placed silicone episcleral encircling element. METHODS: Thirteen patients were retrospectively reviewed. In each patient, a silicone tube was inserted through a small incision into the fibrous capsule overlying the scleral explant. In most patients, no attempt was made to secure the distal end of the tube to the silicone band. The proximal end of the tube was inserted into the eye via a needle track. RESULTS: Successful control of intraocular pressure (IOP) (6 mm Hg < or = final IOP or < 21 mmHg with or without medication) was ultimately achieved in 11 (85%) of 13 patients (3 of the successful patients underwent one or more surgical revisions to relieve obstruction of the proximal and/or distal tube opening). Follow-up in these patients ranged from 8 to 49 months (mean +/- standard deviation, 21.7 +/- 14.1 months). The final postoperative visual acuities were within one line of the preoperative visual acuities or had improved in 11 (85%) patients. Complications included serous choroidal detachment (3 patients; 23%), conjunctival wound leak (2 patients; 15%), hyphema (1 patient; 8%), and tube obstruction by lens, iris, vitreous, or episcleral fibrous tissue (4 patients; 31%). CONCLUSION: Aqueous tube shunt to a pre-existing episcleral encircling element is useful in treating complicated glaucomas after scleral buckling surgery. Fibrous obstruction of the external tube opening is a frequent complication in the early postoperative period, but it may be relieved by surgical revision. PMID- 8008346 TI - Retinal detachment with atopic dermatitis similar to traumatic retinal detachment. AB - PURPOSE: The cause of retinal detachment (RD) with atopic dermatitis remains uncertain. The purpose of this study is to show that the probable cause of RD with atopic dermatitis is ocular contusion. METHODS: The authors retrospectively compared the fundus findings of 24 eyes (16 patients) that had RD and atopic dermatitis with 36 eyes (36 patients) that had traumatic RD. RESULTS: The authors found similar characteristics. Retinal breaks at vitreous base borders characterized by ocular contusion occurred in 79.2% of eyes with RD and atopic dermatitis and in 75.0% of eyes with traumatic RD. Irregular retinal traumatic breaks in the equatorial zone occurred in 20.8% of eyes with RD and atopic dermatitis and in 47.2% of eyes with traumatic RD. Objective signs of ocular contusion outside the retina appeared in 54.2% of eyes with RD and atopic dermatitis. CONCLUSIONS: The authors' data support the conclusion that self inflected ocular contusion by tapping the eyes can cause RD with atopic dermatitis. PMID- 8008347 TI - Vitrectomy for prevention of macular holes. Results of a randomized multicenter clinical trial. Vitrectomy for Prevention of Macular Hole Study Group. AB - PURPOSE: The purpose of this study is to assess the benefit of vitreous surgery in preventing full-thickness macular holes in patients with impending (stage 1) macular holes. METHODS: A prospective randomized multicenter clinical trial was conducted on patients with full-thickness macular holes in their first eye (stage 3 or 4) and signs and symptoms of stage 1 macular holes in their fellow eye (study eye). The study eye was randomized to vitreous surgery or observation. Outcome was assessed by standardized measurement of visual acuity, detailed clinical examination, fundus photographs, and fluorescein angiography. RESULTS: A full-thickness macular hole developed in 10 (37%) of 27 patients in the vitrectomy group compared with 14 (40%) of 35 patients randomized to observation (P = 0.81). This difference of 3% has a 95% confidence interval of (-21%, 27%). CONCLUSION: The study was terminated because of low recruitment. The authors were unable to prove (or disprove) the benefit of vitreous surgery in patients with stage 1 macular holes. The authors can state, however, that should a beneficial effect from vitrectomy exist, it would probably be minimal. Considering the cost and morbidity of vitreous surgery, a conservative approach for stage 1 macular hole might be appropriate. PMID- 8008348 TI - Ten-year incidence of visual loss in a diabetic population. AB - PURPOSE: The purposes of this study are to estimate the 10-year incidence of blindness and visual loss in a diabetic population, examine risk factors for visual loss, and examine temporal trends in rates of blindness and visual loss. METHODS: The design is a population-based cohort study, which includes 891 younger-onset persons with diabetes, 485 persons with older-onset diabetes who are taking insulin, and 502 persons with older-onset diabetes who are not taking insulin and who participated in baseline, 4-year, and 10-year examinations. The main outcome measures are incidence of blindness (visual acuity, 20/200 or worse), doubling of the visual angle, and visual impairment (visual acuity, 20/40 or worse). RESULTS: The 10-year incidences of blindness were 1.8%, 4.0%, and 4.8% in persons in the younger-onset, older-onset taking insulin, and older-onset not taking insulin groups, respectively. Respective 10-year rates of visual impairment were 9.4%, 37.2%, and 23.9%. Rates for doubling of the visual angle were similar. Doubling of the visual angle was more common in women with older onset diabetes and in persons with younger-onset and older-onset diabetes who were taking insulin and who had higher glycosylated hemoglobin or proteinuria levels. The presence of macular edema or more severe retinopathy was associated with more visual loss in all three groups. Smoking was associated with visual loss in persons with younger-onset diabetes, and systolic blood pressure was associated in persons with older-onset diabetes who were taking insulin. Rates of blindness and doubling of the visual angle decreased in persons with younger onset diabetes in the second part of the follow-up. In the older-onset groups, only the rate of blindness declined. These decreases could not be explained entirely by treatment or mortality. CONCLUSIONS: Several modifiable risk factors are associated with loss of vision. Although visual loss is still common in this diabetic population, the incidence of blindness may be decreasing. PMID- 8008349 TI - The influence of combined kidney-pancreas transplantation on the progression of diabetic retinopathy. A case series. AB - PURPOSE: To evaluate the impact of combined kidney and pancreas transplantation on the progression of advanced diabetic retinopathy. METHODS: The changes in diabetic retinopathy severity in patients with insulin-dependent diabetes mellitus who had kidney-pancreas transplantation (n = 51) and in those who had kidney transplantation only (n = 21) were compared. Patients were invited to baseline and 1 year follow-up examinations. Fundus photographs were graded in a masked fashion using standardized protocols. RESULTS: The mean age and duration of diabetes were similar for both groups. After combined transplantation, none of the patients used insulin, and their mean glycosylated hemoglobin was significantly lower (6.4% versus 10.6%) than those who underwent only kidney transplantation. There was a nonsignificant difference in overall progression of retinopathy for combined transplantation compared with kidney transplantation only (risk ratio = 0.73; 95% confidence interval, 0.31, 1.71). CONCLUSION: The authors found no evidence that the normalization of glycemia associated with a combined kidney-pancreas transplantation in patients with advanced proliferative diabetic retinopathy (mostly treated with photocoagulation) accelerated retinopathy progression. These data suggest that the normalization of glycemia associated with a combined kidney-pancreas transplantation does not have beneficial influence on the progression of advanced diabetic retinopathy. PMID- 8008350 TI - Clinical and subclinical ophthalmic findings with retinol deficiency. AB - BACKGROUND: Patients at risk for retinol deficiency in developed countries include those with hepatic dysfunction and malabsorption states. Symptoms of retinol deficiency may go unrecognized or unreported. METHODS: The authors describe 15 patients with hepatic dysfunction, two of whom had procedures that would predispose to malabsorption and were ophthalmologically symptomatic of retinol depletion. The other 13 patients were ophthalmologically asymptomatic liver transplant candidates examined prospectively for subclinical evidence of retinol deficiency. Combined laboratory analysis, Schirmer's testing, conjunctival impression cytology, and electroretinography were performed. RESULTS: Twelve of 15 patients had serum retinol levels below the lower limit of normal. Aqueous tear production was reduced in 7 of 14 patients. Abnormal conjunctival morphology was noted in 6 of 12 patients. Electroretinograms were abnormal in the two patients who were visually symptomatic and in seven of nine patients who were ophthalmologically asymptomatic. CONCLUSION: Subclinical, physiologically significant retinol deficiency may be a frequent and unrecognized problem among patients with hepatic dysfunction. PMID- 8008351 TI - Uveal metastasis from carcinoid tumor. Clinical observations in nine cases. AB - BACKGROUND: Carcinoid tumor is a low-grade malignancy that usually arises in the gastrointestinal tract or bronchus and rarely metastasizes to the eye. Metastasis of carcinoid tumor to the uvea can be confused clinically with other primary and metastatic uveal tumors. METHODS: The authors reviewed the records of 410 consecutive patients with uveal metastases referred to the Ocular Oncology Service at Wills Eye Hospital to identify those in whom carcinoid tumor was the primary neoplasm. The authors evaluated the clinical features of these metastases. RESULTS: Of 410 consecutive patients with uveal metastases, the primary neoplasm was a carcinoid tumor in 9 (2.2%). There were four men and five women. The mean age at ocular diagnosis was 50 years. In five patients (56%), the primary tumor was undiagnosed at ocular presentation. In the other four patients, the mean time interval from diagnosis of the primary carcinoid tumor to uveal metastasis was 89 months (range, 55-180 months). The site of the primary carcinoid tumor was the bronchus in seven patients, the esophagus in one, and the thymus in one. The site of intraocular metastasis was the choroid in six patients, the ciliary body in two, and the iris in one. All choroidal tumors had a characteristic orange color. Initial ocular treatment included external beam radiotherapy in five patients, plaque radiotherapy in two, argon laser photocoagulation in one, and local resection in one. Ocular tumor control was achieved in each patient. After a mean follow-up of 34 months, four patients (44%) are still alive. Five patients have died, with a mean survival of 34 months (range, 2-104 months) after the diagnosis of uveal metastasis. CONCLUSIONS: Uveal metastasis from carcinoid tumor is rare and tends to arise from the bronchus. Clinically, it has a distinctive orange color and may be associated with a longer systemic survival, compared with uveal metastasis from other primary sites. PMID- 8008353 TI - Vascular anatomy of the eyelids. AB - PURPOSE: The eyelids have a rich vascular supply, and bleeding may compromise both surgical technique and postoperative results. Generally, it is known that the eyelids contain a marginal and peripheral arcade, but detailed anatomic information is not available. This study therefore was undertaken to determine the detailed anatomy of eyelid vascularity. METHOD: The common carotid arteries of six fresh cadaver heads were injected with a compound consisting of a partially polymerized monomer, to which a catalyst and promoter were added to cause hardening. The soft tissue was then digested, using 40% potassium hydroxide, to obtain detailed casts of the eyelid arteries, arterioles, and capillaries. RESULTS: The authors describe the eyelid vascularity and anastomotic network with average distance measurements from clinically relevant soft tissue landmarks in the 12 cadaver eyelids. CONCLUSIONS: Consistent patterns of eyelid vascularity were observed. A better understanding of the eyelid vascularity should allow modification of surgical techniques and reduce postoperative complications after eyelid surgery. PMID- 8008352 TI - Endovascular treatment of giant aneurysms which cause visual loss. AB - BACKGROUND: Progressive visual loss that results when a giant cerebral aneurysm compresses the anterior visual pathway requires treatment. When surgical clipping is not safely feasible, percutaneous methods of embolization of the aneurysm can be visual or life saving. METHODS: Endovascular techniques were used to treat 19 of 26 consecutive inoperable giant aneurysms in patients with visual loss, which included optic neuropathy (monocular in 13 patients and bilateral in 8) and optic tract dysfunction in five patients. Embolization of the aneurysm was performed with detachable balloons in 12 patients and with Guglielmi detachable electrocoils in 7. RESULTS: After treatment, vision improved in 7 patients, was unchanged in 11, and worsened in 1. Neurologic complications with balloons were temporary in four patients and severe and permanent in three. In contrast, only one temporary complication occurred with Guglielmi detachable electrocoils. The treatment results are contrasted with the outcome in the seven patients who refused intervention: three hemorrhaged (1 death); monocular blindness with dementia developed in two; a complete homonymous hemianopia and dementia developed in one; and one became bilaterally blind. CONCLUSION: Inoperable symptomatic giant aneurysms can be successfully treated with endovascular treatment. PMID- 8008354 TI - The pupil photostress test. AB - PURPOSE: An objective, pupillographic photostress test was developed to assess the initial sensitivity loss and its rate of recovery in healthy eyes and in eyes affected by optic neuropathy. METHODS: Pupillary light reflexes were recorded with an infrared pupillometer after a binocular photostress that subtended 30 degrees of the central visual field. The initial loss of light sensitivity (in log units) and its recovery with time were derived by analyzing subsequent increases in pupil contraction amplitude to a series of alternating light stimuli. The effects of photostress duration and intensity were studied in ten control subjects. Photostress recovery also was compared between eyes of nine patients with unilateral optic neuropathy. RESULTS: In the ten control subjects, increasing photostress duration caused significantly increased sensitivity loss at time zero after the photostress (analysis of variance), but did not significantly affect the exponential recovery rate. Intense photostress brightness caused more initial sensitivity loss than did dimmer photostress lights. In addition, half-time of sensitivity recovery was prolonged after the brightest photostress. In nine patients with unilateral optic neuropathy, a 120 second photostress caused significantly less initial sensitivity loss in the affected eye than in the healthy fellow eye. CONCLUSIONS: The pupil photostress test objectively can measure the eye's loss of light sensitivity after a photostress and its exponential rate of recovery. Loss of optic nerve function diminishes the initial stress-induced loss of light sensitivity and does not significantly affect the poststress rate of recovery in the patients tested. PMID- 8008355 TI - National study of cataract surgery outcomes. Variation in 4-month postoperative outcomes as reflected in multiple outcome measures. AB - BACKGROUND: Although ophthalmologists have long recognized that visual acuity alone is an inadequate measure of visual impairment, the need for and outcomes of cataract surgery historically have been assessed in terms of visual acuity. PURPOSE: To examine the relation among different cataract surgery outcome measures, including a 14-item instrument designed to measure functional impairment caused by cataract (the VF-14), at 4 months after cataract surgery. METHODS: The authors performed a longitudinal study of 552 patients undergoing first eye cataract surgery by 1 of 75 ophthalmologists practicing in Columbus, Ohio, St. Louis, Missouri, or Houston, Texas. Patients were interviewed, and clinical data were obtained preoperatively (July 15, 1991-March 14, 1992) and 4 months postoperatively. RESULTS: The percentage of patients judged to be improved at 4 months after cataract surgery varied by the outcome measure used: Snellen visual acuity (96%); VF-14 score (89%); satisfaction with vision (85%); self reported trouble with vision (80%); and Sickness Impact Profile score (67%). The change in patients' ratings of their trouble with vision and their satisfaction with vision were correlated more strongly with the change in VF-14 score than with the change in visual acuity (operated eye or better eye). The average change in VF-14 score was unrelated to the preoperative visual acuity in the eye undergoing surgery. CONCLUSION: Estimates of the proportion of patients benefiting from cataract surgery vary with the outcome measure used to measure benefit. Change in VF-14 score, a measure of functional impairment related to vision, may be a better measure of the benefit of cataract surgery than change in visual acuity. PMID- 8008356 TI - Variation in cataract surgery practice and clinical outcomes. AB - PURPOSE: To examine associations between surgical technique, patient and surgeon characteristics, and clinical outcomes of cataract surgery. METHODS: Seventy-five ophthalmologists were recruited from three cities based on a sampling scheme stratified by surgeon-reported annual volume of cataract surgery. Seven hundred seventy-two patients undergoing first eye cataract surgery were enrolled, with complete preoperative, perioperative, and 4-month postoperative clinical data on 717 patients (93%). RESULTS: Sixty-five percent of surgery was performed by phacoemulsification and 35% by standard extracapsular (ECCE) techniques. Performance of ECCE was associated with the presence of ocular comorbidity and 21 or more years in practice of the surgeon. Performance of phacoemulsification was associated with annual volume of cataract surgery, wherein high-volume (201-399 patients annually) and very high-volume (> 400 patients annually) surgeons had 3.7 and 3.9 times the likelihood of performing phacoemulsification compared with moderate-volume (51-200 cases annually) surgeons. The rates of intraoperative, perioperative, and 4-month postoperative adverse events and the amount of improvement in visual acuity did not differ either by surgical technique or volume stratum. The reported occurrence of posterior capsular opacification within 4 months of surgery was increased in the presence of cortical opacification, one city, and patients operated on by either high- or very high volume surgeons. CONCLUSIONS: In this cohort, no difference in clinical outcomes, as measured by change in visual acuity or occurrence of postoperative adverse events (except for posterior capsular opacification), can be attributed to performance of phacoemulsification versus ECCE or to the reported annual volume of cataract surgery of the surgeon. Self-reported high and very high annual volume of cataract surgery is associated independently with performance of phacoemulsification and surgeon's report of posterior capsular opacification at 4 months after cataract surgery. PMID- 8008357 TI - "Recurrent" giant cell arteritis. PMID- 8008358 TI - DUSN occurs in Europe. PMID- 8008359 TI - Surgery for macular holes. PMID- 8008360 TI - Surgery for macular holes. PMID- 8008361 TI - PVD after clear lensectomy for myopia. PMID- 8008362 TI - Relating surgical volume to outcomes of cataract surgery. PMID- 8008363 TI - Human excimer laser keratectomy. Clinical and histopathologic correlations. AB - PURPOSE: To understand the healing capabilities of the diseased human cornea after excimer laser photoablation by morphologic analysis of laser-treated corneas. METHODS: Twelve corneal specimens were obtained 5 to 16 months after lamellar or full-thickness keratoplasty following phototherapeutic keratectomy for undercorrected myopic epikeratoplasty (2 eyes), corneal leukomas (2 eyes), herpes zoster corneal scarring (1 eye), band keratopathy (2 eyes), adenoviral subepithelial opacity (1 eye), keratoconus (1 eye), herpes simplex corneal scarring (2 eyes), granular corneal dystrophy (1 eye), and recurrent lattice dystrophy (1 eye). The morphology of the corneas was examined by light and electron microscopy. RESULTS: Epithelial hyperplasia, abnormal epithelial attachment, and disorganized stromal matrices were observed. Evidence of residual disease frequently observed in these specimens indicated that the pathology either was not excised at the time of laser keratectomy or was recurrent. CONCLUSIONS: The response of the diseased cornea to excimer laser treatment has similar characteristics to the responses previously observed in animal studies. Incomplete ablation of diseased tissue and/or recurrence of the initial disease was the major reason for failure of the treatment. Possible causes for the inability to remove diseased tissues and superficial scars with the excimer laser include (1) insufficiently achieved ablation depth and/or diameter and (2) decreased laser ablation rates of scarred cornea. PMID- 8008364 TI - Randomized clinical trial comparing astigmatism and visual rehabilitation after penetrating keratoplasty with and without intraoperative suture adjustment. AB - PURPOSE: The authors performed a prospective, randomized clinical trial to compare postoperative astigmatism and visual rehabilitation after penetrating keratoplasty with and without intraoperative suture adjustment. METHODS: Twenty five patients undergoing penetrating keratoplasty for avascular corneal pathology randomly were assigned to two groups. All surgery was performed by one surgeon (ONS) using the same technique (except for intraoperative suture adjustment) with Hanna trephination (8 mm) and a running 10-0 nylon suture. Postoperative suture adjustment was done during the first postoperative month in all patients who had more than 3.5 diopters of astigmatism. Refraction and computerized topographic analysis were performed at 1 and 6 months postoperatively. RESULTS: Intraoperative suture adjustment significantly decreased postkeratoplasty topographic (P = 0.0001) and refractive (P = 0.0001) astigmatism and improved best spectacle-corrected visual acuity (P = 0.0019) during the first postoperative month. Seventy-seven percent of control patients (mean topographic astigmatism, 4.89 +/- 1.99 D at 1 month), but no patients who underwent intraoperative suture adjustment (mean topographic astigmatism, 1.50 +/- 0.74 D at 1 month), required at least one postoperative suture adjustment that delayed optical stability and increased postoperative complications. At 6 months postoperatively, mean topographic (P = 0.06) and refractive (P = 0.0001) astigmatism were smaller in the intraoperatively adjusted group than in the control group with postoperative suture adjustments. After intraoperative adjustment, best spectacle-corrected visual acuity was better (P = 0.0168, P = 0.0434) and corneal topography was more regular (P = 0.02, P = 0.07, NS) at 1 and 6 months, respectively, than after postoperative adjustment. CONCLUSION: Visual rehabilitation with decreased postkeratoplasty astigmatism and more regular corneal topography was attained more rapidly and safely with intraoperative suture adjustment. PMID- 8008365 TI - [Transplantation immunology of bone and other collagen-based tissues]. AB - After transplantation of allogeneic bone, cartilage and soft connective tissues different healing processes could be detected depending on the difference of host and graft antigenicities. If the graft antigens were removed completely, HLA, AB0 or Rh matching would not necessary. In case of bone tissue the most important step is the elimination of antigen rich bone marrow and other cells. After transplantation of soft connective tissues with low antigenicity the expected immune response is low. By means of proper pretreatment the antigenicity is diminishable. The best preservation method of bone and soft connective tissues is the freeze-drying. In case of those grafts where the viability of cells is crucial e.g. osteochondral allografts, cartilage, skin, heart valves, the cryopreservation is thought to be the best preservation method. After transplantation immunosuppression is not necessary. The correct donor selection and the graft sterility are the most important, in respect successful clinical application. The evoked immune response generally does not reach that level which could damage graft or host. PMID- 8008366 TI - [Testing the acid-binding capacity of Tisacid suspension and tablets by intragastric pH determination in patients with hyperacidity]. AB - The effect of a Hungarian Al-Mg-containing drug, called Tisacid was studied using of 2.0, 1.0 and 0.5 gram doses. Two administration forms, suspension and tablet were compared. Ten informed, adult hyperacid volunteers were included into the program and three times 5-hour intragastric pH-metry was carried out in a randomized, self-controlled open clinical study (Control, after administration of tablet or suspension). Both forms were found effective in gastric acid reduction at doses of 2.0 and 1.0 g. Tisacid suspension revealed a more pronounced efficacy at the dose of 2.0 g in comparison to the same dose of tablet form. The 0.5 g dose seemed insufficient in reduction of gastric acidity in hyperacid patients applied in tablet or suspension forms. The authors emphasize the role of continuous intragastric pH-metry in clinical practice and investigation of antacids and antisecretory drugs. PMID- 8008368 TI - [Forensic medical expertise in ophthalmologic practice]. AB - The author evaluates 75 cases of his forensic medical expertise as ophthalmologic examiner. He draws attention mostly to those cases which are of interest not only for ophthalmologists but also for other medical specialists. In particular, he investigates the three most frequent groups of cases (questionability of reading capability, injury, detachment of retina), in connection with practical examples. He also discusses questions of defensive medicine as well as the problems of latency between noxa and diagnosis. Besides, he refers to the ophthalmologic aspects of the decreased ability to work. PMID- 8008367 TI - [Ergometric, hemorheologic and myocardial perfusion studies and their evaluation by pattern recognition method in ischemic heart disease]. AB - A large number of noninvasive and invasive methods are used in establishing the diagnosis of ischemic heart disease. Coronary angiography is an expensive method and a restricted capacity exists in Hungary. The aim was to elaborate an optimal combination of different noninvasive methods which can select the real positive cases for coronary angiography with maximal efficiency. Besides routine examinations, dobutamine pharmacological test was carried out and hemorheological parameters were also determined. After evaluating the results, patients were divided into three groups: absence of IHD, probable IHD and IHD. The clustering of patients into these groups was made by using their multivariable classifier algorithm (PRIMA) and 27 different parameters of 44 patients were taken into account. The groups were well separable as the class-distances indicated. The maximal ST segment depression during exercise, pharmacological test and hemorheological parameters were found to be the most powerful discriminating factors. Though the validation of the results is still in progress, based on their previous data they feel that the examination of hemorheological parameters and the application of pattern recognition method can be useful in the diagnosis of ischemic heart disease. PMID- 8008369 TI - [Two cases of extrapulmonary tuberculosis causing differential diagnostic problems]. AB - The decrease of tuberculotic diseases was continuous in the past years. This statement relates to pulmonalis as well as to extrapulmonalis tbc. The authors want to call attention to the possibility of the varied and more rarely appearing extrapulmonalis manifestation. In the first of their cases the burst of spondylitis tbc, and in the other one the very rare spleen tbc--which was made probably clinicum and later by the US abdomen examination--caused differential diagnostic problem. PMID- 8008371 TI - [Does the new nursing legislation bring autonomy to nursing schools?]. PMID- 8008370 TI - [Hungarian history of medicine in computerized databases]. PMID- 8008372 TI - [Nursing--a socially integrating task?]. PMID- 8008373 TI - [The recognition of nursing. How much could be accomplished through nursing if it were more recognized]. PMID- 8008374 TI - [Healthy families for healthy nations. On the International Day of Nursing, 1994]. PMID- 8008375 TI - [Support for women who have taken on some non-professional nursing duties]. PMID- 8008376 TI - [Fathers day, Mothers day, Day of Nursing]. PMID- 8008377 TI - [Thomas Wiesner: "Our purpose is not to show up what is wrong". Interview by Harald Verworner]. PMID- 8008379 TI - Occlusions of VADs: what can you do to intervene? PMID- 8008378 TI - Is "physician extender" part of the advanced practice nurse? PMID- 8008380 TI - How nurse researchers can influence policy. PMID- 8008381 TI - New therapeutic agents marketed in 1993. AB - In 1993, the Food and Drug Administration (FDA) approved 25 new molecular entities (NMEs), 23 of which are for therapeutic use and two are diagnostic agents. Eleven of the NMEs for therapeutic use, as well a new biological agent intended for therapeutic use, were both approved and marketed in the United States in 1993. In addition, 11 other NMEs that the FDA approved before 1993 (most in late 1992) were marketed during the year. Thus, a total of 23 therapeutic agents reached the U.S. market for the first time in 1993, a considerably lower number than the 30 new therapeutic agents marketed in 1992 and the record number 31 new agents marketed in 1991. Many of the 13 therapeutic agents approved in 1993 but not marketed before the end of the year have become available in early 1994. This review of the therapeutic agents first marketed in 1993 considers their most important properties and, when possible, compares them with other available agents with similar properties. Of the 23 new therapeutic agents, 22 are considered in this paper. The one agent not reviewed is flosequinan, which was withdrawn from the market after being available only several months because of a concern about toxicity. This discussion of new drugs focuses on the most important properties of these agents; when additional information is needed, more comprehensive references and the product literature should be consulted. PMID- 8008382 TI - Society offers second drug cost chart. PMID- 8008383 TI - Integrated delivery systems: one staff's experience. AB - Many hospitals and medical staffs have established a physician-hospital organization (PHO) or are discussing the development of one to facilitate contracting with managed care organizations. Physician leadership is essential in the establishment of a PHO in order for physicians to maintain control over patient care. This article describes how one medical staff--at Sewickley Valley Hospital--formed a PHO with its hospital and then a network with other PHOs. It also explains how physicians play an active role in the organization. PMID- 8008384 TI - Negotiate from strength: physician-led integration. The Health Care Group. PMID- 8008385 TI - More details: governor's proposal scrutinized by state society. AB - In the year since announcement of Governor Casey's health system reform proposals, much state as well as national debate has occurred. Last issue, we began a synopsis of the State Society's most recent responses to the governor's proposals, Senate Bill 1202 and House Bill 1958. This is a continuation of that discussion of specific aspects of proposed reform plans for the commonwealth. PMID- 8008386 TI - Reform debate touches Pennsylvania. PMID- 8008388 TI - Recognizing the uncertainty of medicine's future. PMID- 8008387 TI - PMSLIC: focusing on physicians' needs. Pennsylvania Medical Society Liability Insurance Company. AB - The malpractice world is changing, and physicians are asking: How do I choose the right carrier for me? To help physicians answer that and related questions, the chairman of the board of the Society's liability insurance company offers this overview of the company's basic philosophy and focus. PMID- 8008389 TI - AMA releases HIV, smoking guidelines. PMID- 8008390 TI - Q&A supplements new state HIV guidelines. PMID- 8008391 TI - Answers to your questions about employee benefits. PMID- 8008392 TI - Emergency physicians tackle violence. PMID- 8008393 TI - National cooperative projects are new PRO direction: HCQIP. Health Care Quality Improvement Program. PMID- 8008394 TI - The big push. PMID- 8008395 TI - Don't blame Hillary.... PMID- 8008396 TI - Evaluation and management of early HIV infection. PMID- 8008397 TI - Important things to remember about early HIV infection. PMID- 8008398 TI - Women surgical patients report suffering the most. PMID- 8008399 TI - College Misericordia to be funded for rural health initiative. PMID- 8008400 TI - Coalition of nurse educators propose statewide articulation model for Pennsylvania. PMID- 8008401 TI - AZT reduced rate of maternal transmission of HIV. PMID- 8008402 TI - Trigeminal neuralgia: the role of self-sustaining discharge in the trigeminal ganglion. AB - Idiosyncrasies of trigeminal neuralgia provide both clues and constraints on candidate hypotheses concerning the underlying neural mechanism. After reviewing the key clinical aspects of the disease, we propose here a novel hypothesis based on recent findings from experimental nerve-injury preparations. The hypothesis states that trigger stimuli set off bursts of activity in a small cluster of trigeminal ganglion (TRG) neurons that have been rendered hyperexcitable as a result of TRG or trigeminal root damage. Activity then spreads from this "TRG ignition focus" to encompass more widespread portions of the ganglion. After a brief period of autonomous firing (seconds to minutes), activity is quenched and a refractory period is initiated by an intrinsic suppressive (hyperpolarizing) process engaged as a result of the rapid firing. The primary abnormality resides in the TRG and trigeminal root, rather than in the skin or the CNS. Because of this, sensation is essentially normal between periods of ectopic paroxysmal TRG discharge. PMID- 8008403 TI - Altered reactivity of isolated segmental lumbar arteries of dogs following exposure to ethanol and phenol. AB - Celiac plexus neurolysis is a useful analgesic technique in patients with upper abdominal cancer. Although complications are infrequent, occasionally celiac neurolysis results in paraplegia. It is hypothesized that paraplegia after celiac neurolysis results from neurolytic drug-induced spasm of lumbar segmental arteries that perfuse the spinal cord, although no data are available to support or refute the idea. Whether drugs used for celiac plexus neurolysis alter the reactivity of dogs' lumbar segmental arteries was studied in vitro. Rings of lumbar segmental arteries, suspended in Krebs-Ringer solution in organ baths, were passively stretched to the optimal point on their length-tension curve. After a 45-min rest the responsiveness of each ring was established by adding an ED50 concentration of norepinephrine to the bath. Subsequently, Krebs-Ringer solution containing a single concentration of phenol or ethanol was added. Concentrations studied included 1%, 3%, 6%, 7%, 8%, 9%, and 12% phenol; and 3%, 6%, 10%, 25%, 50%, 75%, and 90% ethanol. The magnitude of the phenol-induced contractile response was directly related to concentration, with 8%, 9% and 12% phenol, producing sustained contractile responses compared to norepinephrine induced control contractile responses. The ethanol-induced contractile response was inversely related to concentration. Ethanol (3% and 6%) produced sustained contractile responses compared to norepinephrine-induced control contractile responses. Studies were then done to further elucidate the agonist properties of phenol and ethanol. The contractions caused by ethanol or phenol did not appear to be mediated through adrenergic, opioid, muscarinic, or serotonin receptors or sodium channels.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8008404 TI - Concentrations of morphine, morphine-6-glucuronide and morphine-3-glucuronide in serum and cerebrospinal fluid following morphine administration to patients with morphine-resistant pain. AB - Recent studies have suggested that morphine-3-glucuronide (M3G) may antagonize the analgesic effects of morphine and morphine-6-glucuronide (M6G). To investigate this hypothesis, steady-state concentrations of morphine, M6G and M3G in serum and cerebrospinal fluid (CSF) were measured in 11 patients receiving chronic morphine therapy (9 orally and 2 subcutaneously) for treatment of cancer related pain. All patients appeared to have morphine-resistant pain and had elected to proceed to intrathecal bupivacaine or percutaneous cordotomy. Morphine, M6G and M3G concentrations were measured by high-performance liquid chromatography. The concentrations (median and range) for morphine, M6G and M3G in serum were 193 (14-1086) nmol/l, 847 (210-4113) nmol/l and 4553 (1324-24035) nmol/l, respectively, while in CSF concentrations of morphine, M6G and M3G were 200 (21-1461) nmol/l, 115 (30-427) nmol/l and 719 (249-3252) nmol/l, respectively. Median molar ratios of M6G/morphine and M3G/morphine in serum were 3.79 and 22.1, respectively, while in CSF the same ratios were 0.42 and 2.39, respectively. Median molar ratios of M3G/M6G in serum and CSF were 5.84 and 6.61, respectively. The median molar ratios for CSF/serum distribution of morphine, M6G and M3G were 1.23, 0.12 and 0.14, respectively. Thus, despite their relatively poor ability to penetrate into the CSF, the high serum concentrations of M6G and M3G resulted in substantial concentrations of these metabolites in the CSF. Nevertheless, M3G/M6G ratios in our morphine-resistant patients were similar to published values in patients with well-controlled pain, suggesting that the hypothesis that M3G plays a major role in morphine-resistance is not correct. PMID- 8008405 TI - Low-dose intra-articular morphine analgesia in day case knee arthroscopy: a randomized double-blinded prospective study. AB - The aim of this study was to demonstrate the effect of intra-articular morphine following knee arthroscopy performed in infiltration analgesia. Fifty-two healthy patients were randomized to receive either 1 mg of morphine or placebo. The pain was assessed 2, 4, 8 and 24 h after the procedure by (1) a VAS scale and (2) the amount of acetaminophen consumed. Demographic data in the 2 groups were similar. The pain scores at 8 and 24 h and the acetaminophen consumption after 8 h were lower in the morphine group (P < 0.05). Our results support the hypothesis of peripherally distributed opioid receptors. Stratifying data in therapeutic versus diagnostic arthroscopy indicated additional effect of morphine in patients undergoing therapy (P < 0.1), an aspect supporting the hypothesis of peripherally administered morphine as a potential suppressor of the substance P-mediated cytokine cascade and the peripheral leukocyte activity. Intra-articular morphine (1 mg) after knee arthroscopy offers efficient analgesia lasting more than 24 h. The method is devoid of side effects and deserves wider recognition. PMID- 8008406 TI - Behavioral manifestations of an experimental model for peripheral neuropathy produced by spinal nerve ligation in the primate. AB - A goal of the present study was to document the behavioral changes observed in a model of painful neuropathy in the primate (Macaca fascicularis). A neuropathic state was induced by tight ligation of the L7 spinal nerve, just distal to the L7 dorsal root ganglion. Sensory testing was done on the ventral surface of the foot, a region that includes the L7 dermatome. Within 1 week following surgery, all monkeys (n = 3) developed a marked sensitivity to mechanical stimulation (with a camel hair brush and von Frey hairs), indicating the presence of mechanical allodynia. In 2 animals, the increased sensitivity to mechanical stimulation was also observed on the contralateral side. The threshold for withdrawal to a heat stimulus decreased, indicating the presence of heat hyperalgesia. Presentation of various cooling stimuli, such as acetone and cold water baths, suggested that cold allodynia had also developed. These behavioral phenomena are similar to those seen in humans diagnosed with peripheral neuropathic pain. The behavioral abnormalities are discussed in relation to the responses of spinothalamic tract cells recorded from primates with the same peripheral nerve injury (Palecek et al. 1992). PMID- 8008407 TI - A cerebral blood flow study on tonic pain activation in man. AB - This study examined brain areas involved in tonic pain perception. Cerebral blood flow was assessed by dynamic Xenon-133 inhalation single-photon emission tomography (SPET) in 7 healthy right-handed male volunteers undergoing the cold pressor test (CPT). In single experimental sessions, each subject was scanned twice, once in the resting state and once while immersing the left hand in freezing water (0 degrees C +/- 1). Immersion of the hand induced severe pain (visual analogue scale: 6.9 +/- 1.9) in all subjects. After correction for pCO2, cerebral blood flow was analyzed by placing a template of square regions of interest (ROIs) over 5 selected tomographic slices. Relative to the resting-state values, during the CPT, flow determinations revealed a 7-8% regional blood flow increase in the contralateral frontal lobe and bilateral temporal regions and a 15% flow increase in a ROI located over the primary sensorimotor cortex in the tomogram at 80 mm above the orbito-meatal line (corresponding to the cortical somatotopic representation of the hand) contralateral to the stimulated side. The tonic pain induced by the CPT thus appears to activate the contralateral frontal and bilateral temporal regions and more prominently, the primary sensorimotor cortex. This pattern of activation suggests that tonic painful stimuli activate the cortex partly via complex circuits and partly via direct somatosensory pathways. PMID- 8008408 TI - The cold pressor test in children: methodological aspects and the analgesic effect of intraoral sucrose. AB - To determine whether intraoral sucrose has analgesic-like effects in pre-pubertal children and to explore the utility of an ethical and viable laboratory test of nociceptive stimulation in this age group, 8-11-year-olds (n = 42) underwent the cold pressor test (CPT) at 10 degrees C on each of 2 successive days, while holding either 24% sucrose or water in their months. Outcome measures used were threshold (time at which the arm first started to hurt), tolerance (when children removed their arms because they could not stand it any more) and visual analogue scale (VAS) ratings of the intensity of sensation. To ensure validity of the data obtained in this age group, some responses were rejected according to established decision rules and blind to group assignment. Each measure produced interesting data but also had limitations. Threshold data that did not meet validity criteria occurred more frequently with younger children. Tolerance data was not available for a significant proportion (57%) of children, since they left their arms in the water for the maximum time allowed (4 min). This occurred more frequently on the second day of testing and with younger children. Inability to perform adequately on the VAS also occurred, but was not related to age. Holding sucrose in the mouth was associated with a significant 35% prolongation of the children's threshold times relative to water, but there was no detectable effect on tolerance and intensity ratings. It is concluded that the analgesic properties of intraoral sucrose, seen previously in human newborns and rat pups, may also be present in pre-pubertal children.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8008409 TI - Carrageenan-induced inflammation of the hind foot provokes a rise of GABA immunoreactive cells in the rat spinal cord that is prevented by peripheral neurectomy or neonatal capsaicin treatment. AB - An increase in the number of gamma-aminobutyric acid (GABA)-immunoreactive cells is reported in the superficial dorsal horn of the rat spinal cord upon unilateral inflammation of the hind foot caused by subcutaneous carrageenan injection. The rise of GABAergic cells was restricted to the ipsilateral dorsal horn, reaching a peak value of 23.4% over the contralateral side 4 days after carrageenan injection. Sciatic neurectomy or neonatal capsaicin treatment prevented this effect. These findings suggest that dorsal horn GABA is up-regulated by the increase of noxious inflow conveyed by unmyelinated C fibers from the inflamed tissues. PMID- 8008410 TI - Spinal cord stimulation in Belgium: a nation-wide survey on the incidence, indications and therapeutic efficacy by the health insurer. AB - The present report describes a nation-wide survey on the incidence, the indications and the efficacy of spinal cord stimulation (SCS), as assessed by the Belgian health authorities. The direct motive for this survey was the rapidly growing expenditures resulting from the increasing use of SCS. Between 1983 and 1992, nearly 700 SCS devices were implanted for a population of less than 10 million inhabitants. The most common indication for SCS was failed back survey (61.4%). Whereas SCS was initially only performed in university teaching hospitals, it is now also widely practised in general hospitals. In 3 studies, the efficacy of SCS was assessed. In a first study, success was defined in terms of resumption of professional activities. After a mean follow-up of more than 1 year, less than 5% of the 147 patients treated with SCS had returned to work. A second study investigated the subjective evaluation of the therapy by the patient. Seventy patients with a mean follow-up of 3.5 years were studied. In 52% of the patients, the effect of SCS was judged as good to very good. Men scored better than women. In addition, the results obtained in the teaching hospitals were significantly better than those obtained in general hospitals. In a third study, the impact of psychiatric screening on patient selection was evaluated. Of the 100 candidates, 36 were withheld from implantation with a SCS device because of psychiatric contra-indications. Patients who had received a positive psychiatric advice showed a significantly better therapeutic outcome than patients for whom the psychiatrist had made reservations. PMID- 8008411 TI - A comparison of pain measurement characteristics of mechanical visual analogue and simple numerical rating scales. AB - Numerical rating scales and mechanical visual analogue scales (M-VAS) were compared for their capacity to provide ratio scale measures of experimental pain. Separate estimates of experimental pain sensation intensity and pain unpleasantness were obtained by each method, as were estimates of clinical pain. Orofacial pain patients made numerical scale and VAS ratings in response to noxious thermal stimuli (45-51 degrees C) applied for 5 sec to the forearm by a contact thermode. The derived stimulus-response function was well fit as a power function only in the case of sensory M-VAS. The power function derived from sensory M-VAS ratings predicted temperatures chosen as twice as intense as standard temperatures of 47 degrees C and 48 degrees C, thereby providing evidence for ratio scale characteristics of M-VAS. The stimulus-response function derived from sensory numerical ratings differed from that obtained with M-VAS and did not provide accurate predictions of temperatures perceived as twice intense at 47 degrees C or 48 degrees C. Both M-VAS and numerical rating scales produced reliably different stimulus response functions for pain sensation intensity as compared to pain unpleasantness and both provided consistent measures of experimental and clinical pain intensity. Finally, both mechanical and pencil-and paper VAS produced very similar stimulus-response functions. The ratio scale properties of M-VAS combined with its ease of administration and scoring in clinical settings offer the possibility of a simple yet powerful pain measurement technology in both research and health care settings. PMID- 8008412 TI - Acute and conditioned hyperalgesic responses to illness. AB - It has been argued that pain functions to facilitate recovery from injury and/or illness by stimulating recuperative behaviors. If this is the case, then hyperalgesia might be expected to be part of the constellation of adaptations that occur during sickness. The present series of studies tested two agents that induce illness (lithium chloride and bacterial cell-wall endotoxin (lipopolysaccharide)) to determine their acute effects on pain responsivity in rats. Both agents produced hyperalgesia as measured by the tail-flick and formalin tests. This enhanced responsivity appears to be specific to pain since (a) no enhanced response was observed to a non-painful stimulus (6 g von Frey hairs), and (b) the effect could not be accounted for by changes in tail skin temperature. In addition, a conditioned taste aversion paradigm was used to examine the possibility that illness-induced hyperalgesia could be conditioned to a novel taste (saccharine). This procedure was successful in producing a conditioned hyperalgesia which was comparable in magnitude and duration to acute illness induced pain facilitation. Taken together, this series of studies suggests that such pain facilitation might have adaptive functions similar to those ascribed to other illness-induced behaviors. PMID- 8008413 TI - Slowly developing placebo responses confound tests of intravenous phentolamine to determine mechanisms underlying idiopathic chronic low back pain. AB - Phentolamine (30 mg) was administered intravenously to subjects with idiopathic chronic low back pain in a novel placebo-controlled test to determine whether this alpha-adrenergic antagonist would reduce their pain. The effects of infusions on spontaneous pain and stimulus-evoked pains (touch, cold, tapping and deep pressure) were evaluated separately. All subjects gave strong placebo responses (reduced pain) that prevented assessment of specific drug effects. The placebo responses had onset latencies of 15-60 min, developed slowly over the next 15-45 min and persisted for hours or several days. These results not only reinforce the understanding that placebo controls are essential in the evaluation of drugs or other palliative procedures on patients with chronic pain but also indicate that the control paradigms must allow for placebo effects that are slow to develop and very persistent. PMID- 8008414 TI - Staphylococcal meningitis following Synchromed intrathecal pump implant: a case report. AB - Staphylococcal meningitis associated with implantation of an intrathecal drug pump for spasticity was successfully treated by intrathecal vancomycin delivered by the same pump. This produced high CSF antibiotic levels, and the pump and catheter system did not have to be removed. We are unable to identify a similar case reported in the literature to date. PMID- 8008415 TI - Patient with a lumbar vertebra fracture. Clinical discussion. PMID- 8008416 TI - A simple technique to prevent retrograde ejaculation during assisted ejaculation. AB - The aim of this study was to develop a technique which would prevent retrograde ejaculation in chronic spinal cord injured (SCI) patients undergoing vibration and electroejaculation procedures. A balloon catheter was used to tamponade the bladder neck in 12 patients who underwent 100 assisted ejaculation procedures. Antegrade ejaculations were collected on all occasions with no incidences of urine contamination and no sperm were seen in post ejaculatory urine. Silicone catheters had minimal effects on sperm motility and viability. All lubricant gels were found to adversely affect sperm quality and were not used. PMID- 8008417 TI - Prospective study of pressure ulcer risk in spinal cord injury patients. AB - Sixty men with spinal cord injury who had developed pressure ulcers in the past but whose skin was intact when they joined the study were followed for 2 years, or until a pressure ulcer developed. Forty of the men were contacted every 4-6 weeks to answer questions about their skin care practices and to provide a 24 hour urine sample. The others were only contacted at the beginning and the end of the study to answer a questionnaire and to provide a urine sample. Changes in skin collagen metabolism were monitored by measuring urinary excretion of a metabolite, glucosyl-galactosyl hydroxylysine (glu-gal Hyl), corrected for creatinine excretion. Sustained increases in levels of glu-gal Hyl excretion were detected at least 2 months and as much as 5 months in advance of overt clinical signs of ulcer development. Increased excretion of glu-gal Hyl was significantly associated (p < 0.05) with the development of a pressure ulcer. An increase in the urinary excretion of glu-gal Hyl is an indication of increased degradation of skin collagen. Body mass index (weight/height2) of 33% of subjects with pressure ulcers, and 12% of those without, was at least one standard deviation below the mean of all subjects. Thirty-six percent of those who smoked developed ulcers, while only 26% of the nonsmokers did.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8008418 TI - Development of a tetraplegic hand assessment and splinting protocol. AB - The occupational therapists at the National Spinal Injuries Centre initiated a survey of national and international spinal units in order to investigate which components of hand assessment and which hand splints were most commonly used on patients who have had a spinal cord injury. One hundred and seven questionnaires were sent, but of the 49 returned, only 44 of the assessment questionnaires and 46 of the splinting questionnaires were fully completed and could be used for this study. The results from this survey, the information gathered from the literature and the experiences of the occupational therapists, were used to develop a tetraplegic hand assessment and splinting protocol. This protocol has helped the occupational therapists to be more thorough in their hand assessments, and more discerning with the splints that they make or supply for patients. The low response would suggest that this study should be viewed as a pilot one and that there is need for more valid and reliable research. PMID- 8008419 TI - A survey of spinal cord injuries resulting from sport. AB - We surveyed 35 patients who had been admitted to the Hakone National Hospital with a traumatic spinal cord injury (SCI) resulting from sports accidents, from 1975 to 1991. There were 32 males and three females. Thirty-one patients (88.6%) under the age of 30 had been injured. The most common sport was swimming (51.4%), followed by gymnastics (22.8%). The most common factors were conceit and lack of skill. The injuries were predominantly at the C4-5-6 level. Thirty-four of the patients had a cervical spine injury. Paralysis at the sixth cervical level occurred in 15 cases. Regarding the mechanism of injury, impact on the ground due to misjudgment in the depth of water was the most frequent in swimming; and failure in a somersault the most frequent in gymnastics. The most important point raised in the prevention of SCI sport was education about the dangers during elementary schooling. PMID- 8008420 TI - Anthropometric features of wheelchair marathon race competitors with spinal cord injuries. AB - The anthropometric data of the health check programme in the Oita Wheelchair Marathon Race were analysed. In the past 10 years, a total of 2677 competitors participated in this programme. Age, height, body weight, body fat, lung vital capacity, girth of chest, girth of upper arm, grasping force and power of upper arm were compared between 710 fine competitors and 99 poor competitors. Power of the upper arms and lung vital capacity played a major part in the result of the races. It was suggested that these two factors had major influences on the achievement of this type of sports activity. PMID- 8008421 TI - Ejaculation obtained by intracavernous papaverine in a cervical spinal cord injury patient resulting in pregnancy and childbirth. Case report. AB - A 28 year old male sustained a cervical spinal cord injury (C5, complete) from a traffic accident and was impotent. He started intracavernous injection therapy, by his partner, of papaverine hydrochloride for impotence, restoring ejaculation. His partner had a successful pregnancy after normal sexual intercourse, and delivered a mature female child weighing 3330 g. To our knowledge this is a rare case of a patient with a complete spinal cord injury fathering a child by the above technique. PMID- 8008422 TI - An investigation into the employment and occupation of patients with a spinal cord injury. AB - This study has attempted to ascertain the employment status of a group of 114 expatients with a traumatic spinal cord injury (SCI). The group was 1-7 years post injury. Out of the 114 subjects, 31% were in paid employment and 21% were either in full time education or training. There were 23% unemployed and seeking work and 25% unemployed and not seeking work. Occupations prior to the spinal cord injury were wide ranging throughout all employment categories, with the engineering and science category being most prevalent. Those in employment post injury showed a move towards the administration, clerical and finance categories, with science and engineering also providing some jobs. PMID- 8008423 TI - Group psychotherapy with spinal cord injured substance abusers. AB - Some studies have suggested that nondisabled people follow the dictates of a 'kindness norm' when reacting to those who are disabled. Spinal cord injured substance abusers have sometimes used the kindness of others to help maintain their addictive behavior. A special unit for such substance abusers in a Veterans Affairs hospital has used group psychotherapy as one of the principal methods for moving beyond the kindness norm and challenging its patients to struggle with their substance abuse. Therapists in this group have had to become aware of the special content of denial in this population, of the role of physical problems specific to spinal cord injury, and of the need to set aside clinical issues at times in order to make on the spot responses to practical problems associated with the injury. PMID- 8008424 TI - New findings and symptomatic treatment for neurolathyrism, a motor neuron disease occurring in north west Bangladesh. AB - Neurolathyrism is a form of spastic paraparesis caused by the neuroexcitatory amino acid 3-N-oxalyl-L-2,3-diaminopropanoic acid (beta-ODAP) present in the seeds and foliage of Lathyrus sativus. The disease is irreversible and usually nonprogressive. Tolperisone HCl, a centrally acting muscle relaxant, has been shown to reduce significantly the spasticity in neurolathyrism patients. Sporadic occurrence of HTLV-1 infection (0.9%) and of osteolathyrism was found among the neurolathyrism patients. Osteolathyrism is linked to the consumption of the green shoots of Lathyrus sativus. PMID- 8008425 TI - Aerobic capacity and anaerobic threshold of wheelchair basketball players. AB - This study evaluated the aerobic capacity and anaerobic threshold of national level Israeli wheelchair basketball players. Subjects were tested working on a wheelchair rolling on a motor driven treadmill and on an arm cycle ergometer. Metabolic and cardiopulmonary parameters were measured during graded maximal exercise tests. Blood lactic acid (LA) concentration was measured in the intervals between loads during the test on the wheelchair. Heart rate (HR) and % heart rate reserve (%HRR) corresponding to the anaerobic threshold (4 mM blood LA) were evaluated while working on the wheelchair rolling on a motor driven treadmill. While working on the wheelchair the following peak exercise values were obtained: VO2 = 24.7 ml.kg/min, VE = 92.09 l/min HR = 181.5 b/min and R = 1.22. Values corresponding to the anaerobic threshold were found to be, HR = 139 b/min and %HRR = 57.02. Low correlations were obtained between peak exercise VO2 and VE measured while working on the wheelchair and those measured with arm cycle ergometer (r = 0.57 p = 0.137 and r = 0.4 p = 0.233 respectively). As athletes, subjects in the present study may be classified as having a low aerobic capacity and anaerobic threshold. It is also concluded that the ergometer type may have an important influence on test results. PMID- 8008426 TI - The Standomobile: a new, electrically powered, mobile stand up device for use in paraplegia. Case report. AB - In this case study a specially designed electrically powered mobile stand up device, for a patient with a complete spinal cord lesion under cervical level C7, is described. It has proved to be satisfactory in a flower nursery, where both sitting and standing work is done. It is a usable aid to help patients to return to their work environment. PMID- 8008427 TI - The functional independence measure: a comparative study of clinician and self ratings'. PMID- 8008428 TI - Macaca fascicularis as a model in which to assess the safety and efficacy of a vaccine for periodontitis. AB - We have assessed Macaca fascicularis as a potential model in which to test the efficacy and safety of a vaccine for periodontitis. Twenty-eight animals were surveyed and 20 studied in more detail. Clinical periodontal status was assessed, the subgingival microflora analyzed especially for the presence and proportions of Porphyromonas gingivalis and titers and avidities of serum antibodies reactive with P. gingivalis measured. Probing depths ranged from 0.90 mm to 3.80 mm, Gingival Index scores from 0.00 to 4.00 and Plaque Index scores from 0.00 to 3.00. About 40% of sites bled on probing. The animals manifested a subgingival flora characteristic of the anaerobic gram-negative bacteria found in human periodontal pockets, including Actinobacillus actinomycetemcomitans, P. gingivalis, Bacteroides forsythus, Campylobacter rectus, Prevotella intermedia and Fusobacterium nucleatum. P. gingivalis was detected in 70 of 80 samples studied, ranging from 0.01% to 20% of the total flora. Serum antibody reactive with antigens of P. gingivalis was observed in all animals, with titers ranging from 1.0 enzyme-linked immunosorbent assay (ELISA) unit to 25 ELISA units and avidities from 0.10 M to 2.20 M. Antibody titer and maximum percentage of P. gingivalis were inversely correlated, indicating that a humoral immune response may be effective in reducing P. gingivalis overgrowth. M. fascicularis appears to be an excellent model for use in vaccine development. PMID- 8008430 TI - The most frequently isolated gram-negative anaerobes in saliva and subgingival samples taken from young women. AB - Stimulated saliva and a pooled subgingival sample from the first molars were collected from 30 Caucasian women (mean age 30 years) for the presence of gram negative anaerobic bacteria. The samples were inoculated on nonselective and selective media. The gram-negative anaerobic species occurring in the oral cavity of more than 50% of the subjects were selected for further analysis. Fusobacterium nucleatum and Prevotella melaninogenica were not recovered from subgingival sites without a simultaneous recovery in saliva. When positive subgingivally, Leptotrichia spp., nonpigmented Prevotella spp., Prevotella intermedia, Capnocytophaga spp., Bacteroides gracilis and Prevotella loescheii were simultaneously detected from saliva in 76%, 72%, 64%, 64%, 61% and 55% of the subjects, respectively. Intraindividually, the proportions of F. nucleatum, nonpigmented Prevotella spp., Leptotrichia spp., B. gracilis and P. loescheii of the anaerobic flora were quite similar in the salivary and subgingival samples. Capnocytophaga spp. and P. intermedia were present in higher proportions in subgingival samples than in saliva, whereas P. melaningogenica was present in higher proportions in saliva. Our data indicate that many oral gram-negative anaerobes are frequently recovered from stimulated saliva. Furthermore, when subgingivally positive, most subjects harbored these anaerobes simultaneously in saliva. PMID- 8008429 TI - Evaluation of the E test for antimicrobial susceptibility testing of Porphyromonas gingivalis. AB - The antimicrobial susceptibilities of 81 recent clinical Porphyromonas gingivalis isolates and two reference strains were determined by the E test, a new method, and were compared with the minimal inhibitory concentrations for these strains obtained by the reference agar dilution method on supplemented Brucella blood agar. The following agreements were obtained: benzylpenicillin 100%, ampicillin 96%, cefaclor 82%, cefuroxime 91%, erythromycin 93%, clindamycin 99%, tetracycline 66%, doxycycline 89%, metronidazole 77% and ciprofloxacin 77%. Very major discrepancies were observed with ciprofloxacin. This study indicates that the E test is an acceptable method to determine the susceptibility of P. gingivalis for most antimicrobials. PMID- 8008431 TI - Effect of antibody in gingival crevicular fluid on early colonization of exposed root surfaces by mutans streptococci. AB - The effect of antibody to Streptococcus mutans in gingival crevicular fluid (GCF) on the recolonization of cleaned buccal root surface sites by indigenous mutans streptococci was studied. Seven subjects (mean age = 64 years) were selected from a population of 28 on the basis of the presence of appropriate sites with and without detectable immunoglobulin G (IgG) antibody in GCF to formalin-killed S. mutans and adequate levels of mutans streptococci in saliva available for root surface recolonization. Root surfaces exposed to GCF that did or did not contain antibody were then cleaned and sampled for residual plaque organisms (total cultivable flora and mutans streptococci) directly after cleaning (time 0) as well as 24 h later. One subject failed to recolonize at 24 h at any (antibody positive or antibody-negative) experimental site. For each of the remaining 6 subjects, the mean levels of mutans streptococci (mean percentage of total flora) were lower at sites with IgG antibody to S. mutans in GCF than at antibody negative sites in the same subject. In each of the 6 subjects, the site with the highest recolonization level was antibody-negative. Comparison based on intrasubject randomization of sites suggested diminished recolonization of mutans streptococci at sites with antibody 24 h after cleaning. The results support the idea that antibody in GCF can modify the early colonization of gingival root surface areas by potentially cariogenic plaque bacteria such as mutans streptococci. PMID- 8008432 TI - In vitro activation of the classical pathway of complement by a streptococcal lipoteichoic acid. AB - The purpose of this study was to find whether a glycerolphosphate-containing lipoteichoic acid prepared from Streptococcus sobrinus OMZ 176 cells would activate the classical pathway of complement while in solution. Reference activators were lipopolysaccharide from Escherichia coli 0111:B4 and heat aggregated immunoglobulin G. Serum samples were taken from healthy students. Analysis through crossed immunoelectrophoresis showed that lipoteichoic acid caused an almost complete dissociation of the C1qrs macromolecule. All activators decreased the area of and slowed the electrophoretic mobility of the C4 protein peaks, with lipoteichoic acid causing the most pronounced alterations. Electroimmunoassays showed that lipoteichoic acid separately, yielded detectable amounts of free C1r2s2 subunits; it also generated significantly more trimer complexes between C1r, C1s and C1 inhibitor (C1INH) than did the other two activators. Lipoteichoic acid was, however, a comparatively weak inducer of tetramer C1INH-C1r-C1s-C1INH complexes. Analysis through Western blotting showed that all activators accelerated consumption of C1r, induced complex formations between C1INH and C1s and produced cleavage products of C2. Altogether, the immunochemical analysis gave clear evidence of classical pathway activation by lipoteichoic acid, but its activation profile differed from those seen with lipopolysaccharide and aggregated immunoglobulin G. PMID- 8008433 TI - Bactericidal action of tachyplesin I against oral streptococci. AB - Tachyplesin I, a polycationic antimicrobial peptide isolated from hemocytes of horseshoe crabs, kills bacteria by disrupting the membrane potential of the cytoplasmic membrane. The present study shows that, among 36 oral streptococcal strains, 12 of 21 Streptococcus sanguis, 3 Streptococcus mutans, 9 Streptococcus salivarius and 3 Streptococcus milleri strains were susceptible to tachyplesin I, whereas 9 S. sanguis strains were resistant. Interestingly, these resistant strains include the clinical isolates from both Kawasaki disease and Behcet patients. According to the time-kill study, tachyplesin I inhibited irreversibly the growth of S. sanguis, S. mutans and S. salivarius strains within 20 min and an S. milleri strain within 80 min. Although it has been suggested that Escherichia coli cultured in rich media were more susceptible to tachyplesin I, the present results show that only 3 S. milleri strains were more sensitized to tachyplesin I in a glucose-supplemented medium, and other tested strains were not. Similarly, only 4 strains were more resistant to tachyplesin I in saline than these were in a rich medium. PMID- 8008434 TI - Oxygen-dependent modulation of release and activity of polymorphonuclear leukocyte granule products. AB - Polymorphonuclear leukocytes are important in the defense against the anaerobic microflora of infected gingival pockets. One part of this defense is release of antibacterial granule products by polymorphonuclear leukocytes into the pockets. The aim of the present study was to compare the efficiency of polymorphonuclear leukocytes in releasing granule products under aerobic and anaerobic conditions. Polymorphonuclear leukocytes were exposed to serum-opsonized zymosan under aerobic and anaerobic conditions. The levels of released granule products were determined by combining measurements of activity with enzyme-linked immunosorbent assays. The level of released elastase was twice as high in anaerobic as in aerobic reaction mixtures. A similar difference was not detected for myeloperoxidase. However, myeloperoxidase was inactivated after its release under aerobic conditions. The release of lactoferrin was an efficient under aerobic as under anaerobic conditions. The effect of aerobic conditions on the release of elastase and the inactivation of myeloperoxidase could be ascribed to oxidants formed in the myeloperoxidase-H2O2-chloride system. Also, the activity of the released cytoplasmic enzyme lactate dehydrogenase was inactivated by oxidants formed in the myeloperoxidase-H2O2-chloride system. These findings suggest that, in the anaerobic environment of the gingival pocket, elastase and possibly also other azurophilic granule products are released in higher amounts than under fully oxygenated conditions. In this environment, the released products may also escape inactivation by the myeloperoxidase-H2O2-chloride system. PMID- 8008435 TI - DNA fingerprinting of Eikenella corrodens by pulsed-field gel electrophoresis. AB - In order to conduct molecular typing of Eikenella corrodens strains by macrorestriction fingerprinting, we evaluated different restriction enzymes for digestion of genomic DNA and determined the optimal parameters for separating E. corrodens DNA by pulsed-field gel electrophoresis. Ten E. corrodens strains isolated from oral and extraoral infection sites in different individuals were analyzed. The rare-cutting restriction endonucleases DraI, SmaI and XbaI usually used for pulsed-field gel electrophoresis analyses were not suitable for digestion of E. corrodens genomic DNA because they either did not digest the DNA or produced bands of similar molecular weights that could not be separated. Accordingly, among additional enzymes including BamHI, BglII, EcoRI and Hind III, we found BamHI and BglII to be the most suitable rare-cutting enzymes for pulsed field gel electrophoresis analysis. They cleaved the genomes of all the above strains into 15-20 fragment bands that were clearly separated by the following pulsed-field gel electrophoresis conditions: 140 V with a running time of 40 h, pulse times of 5 to 50 s with linear ramping and an electrical field angle of 120 degrees. These conditions enabled us to distinguish 8 individual pulsed-field gel electrophoresis patterns from the 10 strains analyzed. However, only 4 identical outer membrane protein profiles were differentiated by sodium dodecyl sulfate polyacrylamide gel electrophoresis. The data obtained in this analysis showed clonal divergence among members of the E. corrodens species, at the same time revealing this pulsed-field gel electrophoresis as being a highly attractive procedure for epidemiological investigation of this organism, including its acquisition and transmission. PMID- 8008436 TI - Clonal analysis of Porphyromonas gingivalis by the arbitrarily primed polymerase chain reaction. AB - Genetic analysis of Porphyromonas gingivalis strains may distinguish between virulent and nonvirulent strains and also may be used to trace individual strains in epidemiological studies. The present study examined the utility of the arbitrarily primed polymerase chain reaction for genotypic fingerprinting of P. gingivalis. DNA was extracted according to conventional methods. Ten-base oligonucleotide primers with arbitrary sequences were used with the polymerase chain reaction to amplify P. gingivalis genomic DNA. The amplification products were analyzed by agarose gel electrophoresis. The primer GACCGCTTGT grouped 73 P. gingivalis strains into 23 genotypes, including 16 genotypes containing a single strain each. The primer AGGGGTCTTG identified 45 different genotypes, 33 of which contained a single strain. P. gingivalis strains ATCC 33277T and 381 belonged to the same genotype. Likewise, strains W50 and W83 were of the same genetic clone. The present study indicates that the arbitrarily primed polymerase chain reaction represents a valuable and easy method for clonal analysis of P. gingivalis. PMID- 8008437 TI - Predicting the orthopaedic workforce: Part I. PMID- 8008438 TI - Injection of corticosteroids into joints. PMID- 8008439 TI - Into the knee with needles and steroids. PMID- 8008440 TI - Acute pyogenic osteomyelitis in children. AB - Acute pyogenic osteomyelitis in children continues to be a problem in orthopaedics. The causes of acute hematogenous osteomyelitis are not adequately known, but the histologic progression of the disease has been described. Early diagnosis with culture of an aspiration specimen is of paramount importance. Treatment with antibiotic agents is often successful unless pus is obtained on aspiration. In patients with an established abscess, surgical drainage is often required in addition to antibiotic therapy. Oral antibiotics appear to be as effective as parenteral antibiotics, provided adequate serum bactericidal titers can be demonstrated. Staphylococcus aureus is the most common causative organism, although other organisms are often found in special circumstances, such as in neonates, patients with sickle-cell disease, and those with puncture wounds of the foot. PMID- 8008441 TI - Total ankle arthroplasty. Indications, techniques, and results. AB - A high rate of complications and failure have limited the indications for total ankle replacement to older patients with rheumatoid arthritis, especially those with multiple joint involvement and limited physical activity. Recommended surgical technique for total ankle arthroplasty includes proper patient positioning, an anterior surgical approach, meticulous bone resection, and cemented fixation of components. Results of published studies suggest total ankle arthroplasty should not be performed in patients with posttraumatic arthritis who are younger than 60 years of age. PMID- 8008442 TI - Localized femoral osteolysis in cementless ceramic total hip arthroplasty. AB - A retrospective review revealed localized femoral osteolysis occurred in 8 out of 134 cementless ceramic total hip arthroplasties (6.0%) performed during an average 9-year period. The average latent period was 8 years. The lesion was usually located in the deeper periprosthetic area. Localized osteolysis usually occurred after loosening of the femoral stem, suggesting the pathogenesis may be a foreign-body reaction to the ceramic debris. PMID- 8008443 TI - An osteolytic lesion associated with polyethylene wear debris adjacent to a stable total knee prosthesis. AB - Seven years after total knee arthroplasty, a patient with a well-fixed, uncemented femoral component (cobalt-chromium-molybdenum alloy) developed a large cystic lesion in the distal femur adjacent to the femoral component. This lesion contained fibrotic soft tissue, evidence of a foreign-body giant cell reaction, and a large number of polyethylene particles, but no metal wear debris, infection, or malignancy. PMID- 8008444 TI - A 26-year-old HIV-positive hemophiliac with knee pain. AB - The following case is presented to illustrate the roentgenographic and clinical findings of a condition of interest to the orthopaedic surgeon. Initial history, physical findings, and roentgenographic examinations are found on the first page. The final clinical and roentgenographic differential diagnoses are presented on the following pages. PMID- 8008445 TI - A composite plug for occluding the femoral canal prior to cementing a total hip femoral component. AB - An improved technique is presented for placement of a combined polyethylene and polymethylmethacrylate (PMMA) plug in the femoral medullary canal prior to cementing the femoral component during total hip arthroplasty. PMMA plugs provide excellent occlusion of the canal, but when used alone they often become excessively long. This can make revision surgery, if it becomes necessary, more difficult. By first inserting a polyethylene plug distally in the femoral canal, followed by a bolus of PMMA, the surgeon can limit the length of the cement portion of the plug in the femoral canal while retaining the advantages of a PMMA plug. PMID- 8008446 TI - The code of ethics of the American Dental Association. 1928. PMID- 8008447 TI - Class II, division 2, with posterior crossbite and facial asymmetry. PMID- 8008448 TI - Some observations on the relation between the dental specialist and the general practitioner. 1928. PMID- 8008449 TI - Class II, division 1, malocclusion, subdivision left, with a severe anteroposterior discrepancy. PMID- 8008451 TI - Inhibitory action of the anti-malarial compound atovaquone (566C80) against Plasmodium berghei ANKA in the mosquito, Anopheles stephensi. AB - The activity of atovaquone against Plasmodium berghei ANKA during sporogonic development has been examined. Anopheles stephensi mosquitoes were fed on gametocyte infected mice which had been treated 8 h previously with atovaquone or diluent alone. Mosquito midguts were examined for oocysts, and salivary gland infections were estimated using an ELISA for the circumsporozoite protein (CSP). The number of oocysts per midgut fell by at least 97% when mosquitoes were fed on mice dosed with 0.1-10 mg atovaquone/kg body weight. This was paralleled by a decrease in the prevalence of oocyst-infected mosquitoes from 70-90% in controls to 40% or 10% respectively. No oocysts were observed at a dose of 100 mg/kg. CSP ELISA results indicated that mosquitoes fed on atovaquone failed to produce sporozoites. Mosquitoes which fed on gametocytaemic, atovaquone-treated mice (0.1 100 mg/kg) did not transmit malaria to naive mice. These results demonstrate that atovaquone has a highly potent inhibitory activity against the mosquito stages of P. berghei. PMID- 8008450 TI - Inhibition by anti-malarial drugs of haemoglobin denaturation and iron release in acidified red blood cell lysates--a possible mechanism of their anti-malarial effect? AB - Intraerythrocytic malaria parasites ingest the cytosol of their host cell and digest it inside their acid food vacuoles. Acidified (pH 4-5.5, 37 degrees C) human red blood cell lysates were used to simulate this process, measuring the denaturation of haemoglobin (Hb) and the release of iron, in the absence or presence of exogenous protease. Spontaneous Hb denaturation and appearance of non heme iron were observed upon lysate acidification, their rates decreasing with increasing pH, and increasing in the presence of protease. Both processes were inhibited by the quinoline-containing anti-malarial drugs (QCDs) chloroquine, quinine, mefloquine and amodiaquine at concentrations well below those expected in the acidic food vacuole of the parasite. Spectrophotometric analysis indicated that chloroquine complexes with heme in acid-denatured haemoglobin. Other weak bases as well as verapamil and diltiazem, known to reverse the resistance of malarial parasites to chloroquine, were without effect indicating that the action of QCDs is specific. Based on our previous results and the present report, we suggest that iron release in acidified lysates is mediated through the formation of ferryl (Fe(IV)) radicals. QCDs possibly complex with this radical, as they do with heme, and prevent its contact with an adjacent heme molecule which is required for ring opening and iron release. These results may suggest that one of the anti-malarial effects of QCDs is to deprive the parasite of an adequate iron supply. Addition of iron to cultures of Plasmodium falciparum was expected to circumvent the deprivation of iron and reduce the anti-malarial effect of QCDs. However, adding iron as penetrating fructose or nitrilotriacetate complexes did not alter the parasite's susceptibility to chloroquine. Ascorbate markedly increased the release of iron in acidified lysates, and this effect was not reduced by chloroquine. Ascorbate was found to decrease parasite susceptibility to chloroquine, suggesting that iron deprivation may be an important factor in the anti-malarial action of QCDs. PMID- 8008452 TI - Antibodies to synthetic peptides based on band 3 motifs react specifically with Plasmodium falciparum (human malaria)-infected erythrocytes and block cytoadherence. AB - Rabbit polyclonal and mouse monoclonal antibodies (Mabs) prepared against synthetic peptides patterned on exofacial loops 3 (amino acids 546-555) and 7 (821-834) of the human anion transport protein band 3 inhibited the cytoadherence of Plasmodium falciparum-infected erythrocytes to C32 amelanotic melanoma cells. Mabs directed against exofacial loop 4 (amino acids 628-642) did not inhibit adherence to a significant degree. The murine Mabs recognized only P. falciparum infected cryptic in uninfected erythrocytes. PMID- 8008453 TI - Ricin-resistant mutants of Leishmania major which express modified lipophosphoglycan remain infective for mice. AB - Glycosylation variants of the virulent Leishmania major clone V121 were generated by mutagenesis with N-methyl-N-nitroso-N-nitroguanidine and selected using the galactose-specific lectin Ricinus communis II (RCA II). Three mutants, 4B9, 1D1 and 1C12, which failed to bind RCA II, were found to have an altered expression of lipophosphoglycan (LPG), a molecule implicated in the attachment to host macrophages and survival within the phagolysosome. There were differences in the antigenicity, molecular weight and localization of LPG from mutant parasites as compared to V121. Expression of gp63, a surface molecule also implicated in attachment to macrophages, was unaltered. All 3 mutants caused disease when injected into genetically susceptible BALB/c mice but lesions developed at a much slower rate than those caused by the virulent V121 clone. This slow rate of lesion development did not correlate with promastigotes' ability to invade macrophages in vitro. Karyotype analysis showed that there was a reduction in the size of chromosome band number 2 in all 3 mutants. The differences in LPG and chromosome band 2 were retained by mutant clones following passage through mice, suggesting that these phenotypes are stable. Although the mutant parasites were infective and caused lesions, the changed structure of the LPG appeared to influence the virulence of the parasites. PMID- 8008455 TI - Density-dependent acquired resistance to ticks in natural hosts, independent of concurrent infection with Babesia microti. AB - The question of whether the known immunosuppressive effects of Babesia microti may disrupt the development of acquired resistance to its tick vector, Ixodes trianguliceps, in natural rodent hosts (Clethrionomys glareolus), and thus enhance the disease transmission potential, is addressed experimentally. The results show for the first time that natural hosts can acquire resistance to ticks; that this acquired resistance is manifested chiefly by a strongly density dependent reduction in the percentage of attached larvae that engorge; that the density dependence is quantitatively similar whether the host receives occasional large tick challenges or frequent low infestations; but that infection with B. microti does not disrupt this pattern of acquired resistance. Of two important natural host species, Apodemus sylvaticus can support repeated infestations of I. trianguliceps, but is a poor host to B. microti, while C. glareolus develops acquired resistance to the tick vector, but supports much higher-level, longer lasting B. microti infections. PMID- 8008454 TI - Prevalence and transmission of Toxoplasma gondii in wild brown rats, Rattus norvegicus. AB - Prevalence of Toxoplasma gondii within 6 UK farmstead wild rat populations, and 1 population maintained within a captive cat-free environment for 2.5 years, was examined. The mean prevalence found was 35% (n = 235), which is more than 3 times as high as all other wild rat prevalence levels previously reported in the UK. There were no significant age, sex or site differences in prevalence between or within populations irrespective of habitat type or presence of cats. Toxoplasma was also maintained within the captive rat population in the absence of cats at a prevalence, intensity, age and sex distribution similar to that of the farmstead rat populations. These results suggest, firstly, that Toxoplasma can be perpetuated within wild rat populations without the sympatric presence of cats and secondly, that the congenital route is the predominant route of transmission in wild rats. This study concludes that wild rats represent a significant and persistent wildlife intermediate host reservoir for toxoplasmosis. PMID- 8008456 TI - Sarcocysts (Sarcocystis sp.: Sporozoa) in the European badger, Meles meles. AB - Sarcocysts from the tongue muscle of a European badger (Meles meles) are reported for the first time and described by light and transmission electron microscopy. Judging from the ultrastructure of the cyst wall, the parasite is similar to the species Sarcocystis gracilis Ratz, 1909 sensu Erber, Boch & Barth (1978) from roe deer and possibly identical with it. This is noteworthy regarding the intermediate host specificity. PMID- 8008457 TI - Serotonin and its requirement for maintenance of contractility in muscle fibres isolated from Schistosoma mansoni. AB - Muscle fibres isolated from adult Schistosoma mansoni contracted in a dose dependent manner when exposed to elevated K+ with a maximum response obtained with 25 mM K+. These contractions were dependent on extracellular Ca2+ since Co2+ (5 mM) or nicardipine (1 microM) blocked the high K+ contractions. Serotonin (300 nM or higher) was required for maintenance of high K+ contractions. With concentrations of serotonin less than 300 nM the response was dose dependent. 5 Methoxytryptamine or alpha-methylserotonin at 1 microM as well as 10 microM tryptamine were able to substitute for serotonin, but 1 microM 5 carboxyamidotryptamine was ineffective. The order of potency for antagonists (10 microM) was: methiothepin > metergoline > Ly-278,584 = ketanserin. This pattern of responsiveness does not fit well with any known mammalian serotonin receptor subtype. Since forskolin, an adenylate cyclase activator, is able to mimic the action of serotonin and H89, a protein kinase inhibitor, is able to block the effect of serotonin, the effect of serotonin on contractility of the muscle may be via a cAMP-dependent pathway. PMID- 8008458 TI - Infrapopulation dynamics of Gyrdicotylus gallieni (Monogenea: Gyrodactylidae). AB - Gyrdicotylus gallieni is a viviparous gyrodactylid monogenean that infects the buccal cavity and pharynx of Xenopus laevis laevis. Offspring directly recolonize the same host as their parent and transmission is carried out exclusively by adult worms which are capable of leech-like stepping locomotion. The infrapopulation dynamics (at 20 degrees C) of this species were studied by experimental exposure to single worms of previously uninfected hosts (which were dissected at various time-intervals post-infection). Infrapopulations increased exponentially until 50 days post-infection (p.i.), during which time the intrinsic rate of increase was estimated by regression as 0.065/parasite/day. After this, infrapopulation sizes showed greater variability, with established infections becoming extinct 2-5 months p.i.: elimination was probably due to some form of host reaction, as parasite lineages were maintained for up to 10 months by transfers to successive uninfected hosts. The development of infrapopulations is similar to that reported for other viviparous gyrodactylids parasitic on the body surface of teleosts. However, the intrinsic rate of increase was comparatively slow in G. gallieni and the duration of infection in isolated hosts prolonged. Slow-growing infrapopulations may elicit a host response more slowly and extend the period during which dispersal to a new host or host population can occur. This might be important in G. gallieni for which the internal site of infection could limit the transmission rate, as worm migration from the oral cavity or accidental detachment and expulsion is necessary for host-host transfer to occur.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8008459 TI - The effect of homogenates and excretory/secretory products of Nippostrongylus brasiliensis and of acetylcholinesterase on the amplitude and frequency of contraction of uninfected rat intestine in vitro. AB - Whole worm homogenates and excretory/secretory (E/S) products of adult Nippostrongylus brasiliensis significantly decreased the amplitude of contractions of segments of uninfected rat intestine maintained in an organ bath, with significantly larger volumes of E/S products being required to bring about a similar decrease to that caused by the whole worm homogenate. Boiled samples of homogenate and E/S products significantly decreased the amplitude of contractions of uninfected rat intestine, but larger volumes were needed than with unboiled samples. Frequency of contraction was unaltered by homogenates or E/S products. When electric eel AChE was injected into the lumen of segments of uninfected rat intestine maintained in an organ bath there was no significant decrease in the amplitude of contractions. These results suggest that substances present in the E/S products of N. brasiliensis significantly reduce the amplitude of contractions of uninfected rat intestine in vitro and that the biochemical holdfast responsible for this phenomenon may not be AChE. PMID- 8008461 TI - Effect of metacestodes of Hymenolepis diminuta on storage and circulating carbohydrates in the intermediate host, Tenebrio molitor. AB - The metamorphosis of oncospheres of the rat tapeworm, Hymenolepis diminuta, to mature metacestodes induces several pathophysiological effects in the intermediate host, Tenebrio molitor (Coleoptera). Previous investigations have failed to elucidate the mechanism responsible for changes in the host reproductive physiology and behaviour. This work forms part of an assessment of the degree to which nutrient resource management may be involved in these interactions. We report that developing metacestodes exert a pronounced effect upon host carbohydrate reserves and also alter circulating carbohydrate titres at some stages post-infection. Biochemical studies of fat body glycogen demonstrated a significant depletion of reserves as early as 3 days post-infection in males and 5 days post-infection in females. Gas chromatography revealed trehalose to be the predominant haemolymph carbohydrate, titres being significantly elevated in male beetles 5 and 9 days post-infection and in females 12 days post-infection. Metacestodes had no effect on glucose concentrations in male or female beetles. PMID- 8008460 TI - Immunological relationships during primary infection with Heligmosomoides polygyrus: Th2 cytokines and primary response phenotype. AB - The primary immune response to infection with Heligmosomoides polygyrus was studied in mice differing in response phenotype (fast-SWR, intermediate-NIH, slow CBA). Marked IgG1 and IgE but not IgG2a antibody responses were detected in infected mice and the former were more intense in fast compared with slow responder strains. Mastocytosis, MMCP-1, and the secretion of cytokines by mesenteric lymph node cells, following stimulation in vitro by Con A, were also more intense initially in SWR mice. Secretion of IL-4 declined in all strains by the 4th week of infection, irrespective of response phenotype. IL-10 was only produced briefly by SWR mice. However, the temporal patterns of secretion of IL-3 and IL-9 clearly distinguished fast from slow responder phenotypes. Following initial intense secretion of IL-3, production declined in all strains but in the 5-6th weeks enhanced secretion was evident in SWR and NIH mice and was sustained until week 10 p.i. In contrast, CBA mice never recovered from the initial down regulation in weeks 3-4 and secretion declined to background levels by week 6 p.i. despite the continued presence of adult worms. Temporal changes in the secretion of IL-9 were very similar: secretion declined in CBA mice by week 6 p.i., whilst SWR and NIH mice continued to secrete high amounts. We suggest that fast and slow responder mice differ not only in their initial responsiveness to parasite antigens but also in their ability to sustain a Th2 response to the parasite and we propose that the latter is in part determined by their different susceptibilities to parasite-mediated immunomodulation. Only the fast responder strains can sustain a Th2 response of sufficient intensity to facilitate expulsion of adult worms. PMID- 8008462 TI - The detection of AKH/HrTH-like peptides in Ascaridia galli and Ascaris suum using an insect hyperglycaemic bioassay. AB - Evidence for the presence of adipokinetic hormone/hypertrehalosaemic hormone (AKH/HrTH)-like peptides in the parasitic nematodes Ascaridia galli and Ascaris suum has been obtained using insect bioassays which measure hyperglycaemic responses to peptides belonging to the AKH/HrTH family of insect hormones. A peptide fraction extracted from heads and tails of Ascaridia galli evoked a dose dependent hyperglycaemic response when injected into the cockroach, Periplaneta americana. Maximal bioactivity was obtained with material that was equivalent to 38 mg (wet weight) of nematode. Bioactivity appeared to be highest in extracts from heads and tails of both male and female worms and could be fractionated into at least three peaks of hyperglycaemic activity by reversed-phase high performance liquid chromatography. An extract from heads and tails of A. suum also evoked a hyperglycaemic response when injected into the cockroach, Blaberus discoidalis. The bioactivity was inactivated on incubation with pure endopeptidase 24.11, confirming the peptidic nature of the bioactive material. These results provide evidence for the existence of peptides related to the insect AKH/HrTH family of peptides in parasitic nematodes. PMID- 8008463 TI - Pyloric stenosis is a pediatrician's diagnosis. PMID- 8008464 TI - Pediatric trauma. AB - Injured children require an organized team approach to provide the best possible care. To accomplish this, physicians in all specialties must be knowledgeable about prevention strategy, patterns of injury, and state-of-the-art treatment techniques. Improvements are still needed in several areas including vehicular restraint systems and bicycle helmet regulations. Rehabilitation services are currently inadequate to meet many of the needs of the children and their families when disabilities are permanent. Unless efforts to improve these deficiencies are continued, the tragedy of childhood injury will not diminish. Physicians who care for children have a responsibility to help decrease the incidence of trauma in their area and to help improve the management of the injured child to assure the best potential outcome. PMID- 8008465 TI - Acute surgical conditions of the abdomen. PMID- 8008466 TI - Acute surgical conditions of the chest. PMID- 8008467 TI - Acute urologic conditions. PMID- 8008468 TI - Learning new ways to communicate. PMID- 8008469 TI - Assessment and management of status asthmaticus. AB - Asthma is one of the most common chronic diseases of childhood. The incidence of hospitalizations for acute exacerbations are increasing. Status asthmaticus is a medical emergency that can result in respiratory failure and death if not treated properly. An understanding of the pathophysiology of asthma and an acute exacerbation lay the foundation for competent nursing care. An accurate assessment includes a rapid and thorough history, evaluating the level of consciousness, respiratory effort, vital signs, oxygen saturation, arteria blood gases, and peak expiratory flow rates. Management issues include standard pharmacologic interventions and other therapies, hospital admission, controversial pharmacologic management, assisted ventilation, psychosocial care, and education. PMID- 8008470 TI - Children's perspectives on coping with asthma. AB - Little is known about how children with asthma perceive their own ability to cope with asthma symptoms. A descriptive study of children with asthma (N = 78) attending a camp in the Midwest sought to identify the frequency and effectiveness of coping strategies that school-age children use when having a problem with asthma. A self-report instrument, the Schoolagers' Coping Strategies Inventory (SCSI), was used to measure coping strategies from the children's perspective. Results indicated that 4 of the 5 most effective strategies were also used most frequently, including "try to relax or stay calm," "watch TV or listen to music," "do something about it," and "say I'm sorry or tell the truth." Self-report information about coping strategies adds important data to nurses' assessment of children with asthma. PMID- 8008471 TI - Nursing mothers service: a community breast-feeding program. AB - An upward trend in breast feeding has been seen in recent years, and health care providers must take an active role in providing services to lactating women if this trend continues. A nurse managed, hospital-based, breast-feeding program that provides continuity of care and supportive services from the hospital to the community for lactating women is described. PMID- 8008472 TI - Safe delivery of medications to children in summer camps. AB - Summer camps should be a safe and fun experience for children. Each year, many nurses assume the responsibility for health care of campers and are faced with a variety of medication and clinical challenges. This survey of medication practices in summer camps revealed a need for improved collaboration among camp personnel, families, and primary care providers. The findings of this study indicate a need for improved communication about medications among all the parties involved to ensure continuity of health care. Pediatric nurses have the opportunity to be proactive by providing parents and children with strategies to assure the best possible summer camp experiences. PMID- 8008473 TI - Clinical case study: pediatric gas gangrene. AB - Gas gangrene is a rare, serious infection. Untreated, it can rapidly be fatal. Accurate nursing assessments and timely interventions are needed to prevent loss of limb and potential loss of life. PMID- 8008474 TI - Pediatric management problems. Asthma. PMID- 8008475 TI - Childhood near-drowning: nursing care and primary prevention. AB - Young children continue to be victims of drowning and near-drowning. The pediatric critical care nurse is often called upon to care for a child following a near drowning event. The role of the nurse in assessment, early intervention and continuing critical care management, and primary prevention of water-related injuries are reviewed. PMID- 8008476 TI - Home care management of the child with infantile spasms. AB - The child with infantile spasms is at considerable risk for side effects related to ACTH therapy. Careful evaluation and assessment skills are essential in managing this group of patients following discharge. PMID- 8008477 TI - Pulmozyme--Dornase alfa. AB - Dornase alfa is the first new drug released in 30 years for the treatment of patients with CF. Although it does not represent a replacement for current standard therapies, it is an effective agent in improving lung function. The development of this drug has helped to provide treatment to a medical problem that physicians have struggled with treating for years. PMID- 8008478 TI - Is there hope for teen pregnancy in America? PMID- 8008480 TI - Intranasal versed: the future of pediatric conscious sedation. AB - Conscious sedation of pediatric patients for procedures is occurring with increasing frequency in hospitals and outpatient settings. Nurses need to be aware of current AAP guidelines for conscious sedation as well as current trends in medication. The pediatric applications and current literature regarding intranasal midazolam and flumazenil are reviewed. PMID- 8008479 TI - Anencephalic newborns: legal and ethical comments regarding the matter of Baby "K". PMID- 8008481 TI - Death of a sibling: primary care interventions. AB - The death of a child is difficult for nurses and other health care professionals. Responses of children who have experienced the death of a sibling have both affective and cognitive components. Practice considerations from both of these domains are addressed here. PMID- 8008482 TI - Perceptions of nurses and physicians regarding pain management of pediatric emergency room patients. AB - PURPOSE: To explore perceptions of pain and pain management by nurses and physicians who care for pediatric emergency room patients. METHOD: A descriptive survey design using the Adapted Klein Premedication Questionnaire explored the attitudes and practices of 24 nurses and 21 physicians about children's pain in the emergency setting. RESULTS: The majority of nurses and physicians who care for pediatric emergency room patients would medicate children experiencing pain. Both groups perceived pain in children the same way. There was a lack of knowledge in both groups regarding the appropriate dosages of pain medications. CONCLUSIONS: Nurses and physicians need a stronger knowledge base regarding pain management practices. PMID- 8008483 TI - "Chunky stew:" appreciating cultural diversity while providing health care for children. AB - The United States does not have as clear a generalized culture as more homogenous nations. For this reason, cultural competence is an important goal of nursing practice. Culture and ethnicity affect access to care and use of health care services. The cultural biases of the health care system must be acknowledged so that nurses can dialogue effectively with families who may have different perceptions. Cultural differences in the perceived meaning of illness affect both help-seeking behavior and approaches to caring and curing. Cross-cultural communication includes attention to language differences and jargon, as well as sensitivity to the family's values and preferences. Intervention plans for the child should be developed in conjunction with the family and should reflect their choices and address their concerns. PMID- 8008484 TI - Comparison of stimulable phosphor technology and conventional screen-film technology in pediatric scoliosis. AB - One hundred consecutive patients being investigated for scoliosis were studied using a double cassette containing a conventional film screen and a stimulable phosphor plate. The images were separated, randomised and scored thrice by three radiologists for anatomic structure visualisation. The exposure to the plate and film and repeat rate were measured. Scoliosis angles were comparable on both sets of images, however, visualisation of vertebrae, vertebral end plates, pedicles, spinous processes and other structures were significantly improved (p < 0.0001). Intra- and inter-observer reliability was high with good intraclass correlation. There was a 40% potential exposure reduction, and retakes were decreased from 3 to 0%. We conclude that stimulable phosphor images give better anatomic structure visualisation with potential radiation exposure reduction and lower repeat rate. PMID- 8008485 TI - Ultrasound evaluation of uterine and ovarian size from birth to puberty. AB - Sonographic measurement of uterine and ovarian volume was performed in 178 healthy girls ranging in age from newborn to 14 years. High values were measured during the neonatal age and puberty, in contrast to those in subjects between 1 month and 7 years of age. We conclude that age and pubertal stage are important parameters in correctly interpreting the size of the uterus and ovaries in childhood. PMID- 8008486 TI - Ultrasound screening of older asymptomatic siblings of children with vesicoureteral reflux: is it beneficial? AB - The purpose of this prospective study was to determine the prevalence of renal abnormalities in 88 older asymptomatic siblings of the children with vesicoureteral reflux (VUR), using ultrasound (US) as a diagnostic method. The age of the siblings ranged from 5 to 15 years, the median age being 8.33 years. A midstream urine sample was taken for standard urinalysis and urine culture, and blood pressure was measured in all children. US examination did not reveal chronic inflammatory changes of the kidneys such as a small shrunken kidney, noticeable parenchymal thinning or parenchymal echogenicity changes; nor did it reveal a small kidney due to growth retardation or any dilatation of the renal tract to indicate reflux. No hypertension was found. The study failed to prove the benefit of US screening of older asymptomatic siblings. The results of the present study are discussed in relation to other techniques and investigations/screening for VUR. PMID- 8008487 TI - Plain abdominal radiography in suspected intussusception: a reassessment. AB - The objectives of the study were (1) to determine the interobserver variation in interpretation of abdominal radiographs in children with clinically suspected intussusception, and (2) to determine the diagnostic value of abdominal radiographs in these patients. One hundred and eighty-two plain abdominal radiographic examinations (AXR) performed in children with clinically suspected intussusception were reviewed blind to the clinical history and findings of air enema. The presence or absence of nine AXR signs relevant to intussusception was documented. Each AXR was categorized as equivocal, positive or negative for intussusception, with the aim of achieving no false negatives. Interobserver variation in the identification of AXR signs and radiologic diagnoses was calculated using the kappa statistic for 60 cases assessed independently by three observers. Using the findings of air enema as gold standard, the prevalence of AXR signs in all patients with (60) and without (122) intussusception was determined and their diagnostic values calculated. The best observer agreement was for the presence of sparse small bowel gas (supine, k = 0.68) and the worst for the presence of cecal gas (erect, k = 0.18). All three observers agreed intussusception to be present or absent in only 7 of 60 cases and the majority agreement was equivocal in more than half. Overall agreement between observers for the diagnosis of intussusception was k = 0.30. The best positive predictors of intussusception were the soft tissue mass and sparse large bowel gas, with likelihood ratios of 3.9 and 2.5. Cecal feces predicted against intussusception, likelihood ratio 0.11. AXR was equivocal in 53%, positive in 21% and negative in 26%. Where a firm radiographic diagnosis was made, the diagnostic accuracy of AXR was 84%.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8008488 TI - Ultrasound-guided pediatric liver transplant biopsy using a spring-propelled cutting needle (biopsy gun). AB - Biopsy is the best way to diagnose allograft rejection, the most common complication following liver transplantation. The authors reviewed 99 consecutive ultrasound-guided cutting needle biopsies in 19 infants and children. Conscious sedation was used with 95 biopsies. General anesthesia was used with four biopsies, all in patients undergoing percutaneous biliary procedures at the same time. Ninety-eight biopsies were diagnostic. Only one major complication occurred: biloma. Ultrasound-guided cutting needle biopsy of pediatric liver transplant patients can be performed safely and efficaciously. PMID- 8008489 TI - The value of radionuclide splenic scanning in the evaluation of asplenia in patients with heterotaxy. AB - Splenic anomalies frequently accompany conotruncal and atrioventricular septal malformations. Asplenia is a major factor in the mortality of newborns with the heterotaxy syndrome, requiring an early and accurate diagnosis. We evaluated the splenic status of five consecutive patients with heterotaxy syndrome by radionuclide splenic scanning with 99mTc-labelled and denatured red blood cells (RBCs) and by real-time abdominal ultrasonography. Examination and comparison of the findings using these diagnostic methods suggest that the former has some diagnostic pitfalls which arise from the symmetrical location of the liver in the abdomen. This leads to difficulty in the interpretation of overlapping signals from the blood pool of the liver and from the spleen. PMID- 8008490 TI - Langerhans cell histiocytosis of bone: MR imaging. AB - Magnetic resonance (MR) images of 12 pathologically proven lesions of Langerhans cell histiocytosis (LCH) of bone were reviewed retrospectively. MR identified all lesions, three of which were not identified on plain radiographs. In all cases, MR showed greater abnormality than did plain radiographs. With one exception, all lesions were hypointense on T1-weighted images and hyperintense on T2-weighted images. The lesions and associated soft tissue abnormalities were very conspicuous on short TI inversion sequences and T1-weighted post-contrast images. Follow-up MR studies in two patients after chemotherapy showed decreased size and enhancement of lesions compared with baseline studies. PMID- 8008491 TI - Eosinophilic granuloma of the head and neck: CT and MRI features in three cases. AB - We report the radiological findings and more specifically the MRI features in three typical cases of Langerhans' cell histiocytosis of the head and neck. All three cases were of solitary eosinophilic granuloma of bone: two mandibular and one temporal bone lesion. Reports on the MRI features of head and neck eosinophilic granulomas are rare. PMID- 8008492 TI - Stress fracture of the great toe sesamoid in a ballerina: MRI appearance. AB - This case is the first to depict a stress fracture of the great toe sesamoid bone using magnetic resonance imaging. We used a 3" surface coil to produce high resolution images of the sesamoid. PMID- 8008493 TI - Arterial and venous compromise by an osteochondroma. AB - A 9.5-year-old girl had popliteal arterial and venous compression by a distal femoral osteochondroma. Magnetic resonance imaging demonstrated the relation of the vessels to the osteochondroma and a three-phase bone scintigram showed asymmetry of arterial perfusion and evidence of venous stasis. PMID- 8008494 TI - Relationships between coronary artery dilatation and severity of carditis detected by two-dimensional echocardiography and [99mTc]HMPAO-labeled white blood cell heart scan in children with Kawasaki disease. AB - Forty-one children (15 girls, 26 boys; ages 3.0 +/- 2.1 years) with Kawasaki disease (KD) were included in our study. The diameters of a total of 82 coronary arteries (CA), comprising 41 left (LCA) and 41 right (RCA), were computed by two dimensional echocardiography (2D-Echo). If the diameter of the CA was > or = 20 mm, it was considered as dilated. The severity of the carditis was evaluated by [99mTc]HMPAO-labeled white blood cell (WBC) heart scans (Tc-WBC) carried out in all cases. On the basis of the results the children were divided into three groups. Group A children had the most severe carditis where the heart uptake was greater than the bone uptake; 11 of 32 (34.3%) of the CA in 16 cases were dilated. Group B had carditis of medium severity where the heart uptake was equal to the bone uptake; 11 of 28 (39.3%) of the CA in 14 cases were dilated. Group C had mild carditis where the heart uptake was less than the bone uptake; 9 of 22 (40.9%) of the CA in 11 cases were dilated. There were no significant differences among the three groups (p = 0.87 by a chi-squared test). We conclude that no definite relationship exists between the severity of carditis and the dilatation of the CA in children with KD. PMID- 8008495 TI - Prostaglandin-induced foveolar hyperplasia simulating pyloric stenosis in an infant with cyanotic heart disease. AB - Prostaglandin infusion is used to maintain patency of the ductus arteriosus in infants with cyanotic congenital heart disease. Recently, gastric outlet obstruction as a result of prostaglandin infusion has been described. In our case, an upper gastrointestinal contrast study seemed to depict the typical appearance of pyloric stenosis in an infant who had received an infusion of prostaglandin for a prolonged period. Serial ultrasonograms, however, disclosed progressive elongation of the antropyloric channel without wall thickening. This report is the second to illustrate prostaglandin-induced gastric outlet obstruction in a vomiting infant with a gastrointestinal series diagnosis of pyloric stenosis. PMID- 8008496 TI - Atelosteogenesis type III: a case report. AB - We present a case of rhizomelic dwarfism with clinical, radiographic and histologic features in keeping with atelosteogenesis type III (spondylohumerofemoral hypoplasia). Unlike most other skeletal chondrodysplasias presenting with neonatal dwarfism, a proportion of patients with atelosteogenesis type III may survive well beyond the neonatal period, and hence early identification of the condition is important. Our surviving patient further defines the radiographic features of the condition and the natural history and prognosis for physical and intellectual disability. PMID- 8008497 TI - Rhinocerebral mucormycosis in a child with leukemia: CT and MRI findings. PMID- 8008498 TI - Sacrococcygeal teratoma: a case of mistaken identity. AB - We report a case in which prenatal diagnosis of fetal myelomeningocele led to termination of the pregnancy at 17 weeks. The diagnosis was made on the basis of prenatal ultrasound scan and raised maternal alpha-fetoprotein. Although the large cystic lesion arising in the sacral region appeared to confirm the diagnosis, autopsy examination revealed that this was a cystic sacrococcygeal teratoma. This case illustrates the importance of submitting all fetuses for full autopsy. PMID- 8008499 TI - Congenital mesoblastic nephroma presenting with hemoperitoneum and shock. AB - We describe an unusual presentation of a congenital mesoblastic nephroma in a 5 month-old boy. He was in hemodynamic shock in admission. Sonography revealed an echogenic right kidney and hemoperitoneum. Right nephrectomy was performed, and he is well one year later without any further treatment. PMID- 8008500 TI - Osteopathia striata with cranial sclerosis. AB - Osteopathia striata with cranial sclerosis (OS-CS) is a specific bone dysplasia manifested by hypertelorism, flat nasal bridge, frontal bossing, large head, hypoplastic maxilla, palate anomalies, chronic otitis media, hearing deficits, nasal obstruction, and neurological changes of deafness, facial palsy, ophthalmoplegia, and mental retardation. We will review the clinical and radiologic findings in a new patient from birth to 20 years; this is believed to be the thirty-fifth patient reported. OS-CS is 2.5 times more common in females and occurs as an autosomal dominant condition or a sporadic dominant mutation with patients presenting for evaluation from the newborn period to the fifth decade. Skeletal abnormalities are distinctive including sclerosis of the skull base and calvarium, linear striated densities in the long bones and pelvis, and poor development of the mastoid and sinus air cells. Radionuclide bone scans with SPECT indicated in our patient increased bone turnover which was supported by biochemical findings of increased pyridinoline excretion. The major complications are due to constriction of essential foramina at the skull base. The condition is not life-threatening but can produce disability. PMID- 8008501 TI - Feasibility of high-resolution, low-dose chest CT in evaluating the pediatric chest. AB - Thin-section, high-resolution (1.0/1.5 mm thick slices), low-dose chest CT scans were performed in 55 infants and children. The studies were carried out with 1- and 2-s scan (data acquisition) times using a high-resolution (bone) algorithm. Although there was some motion artifact, the studies provided valuable information for evaluating diffuse parenchymal lung disease. The thin slices provided finer detail and more diagnostic information than images representing thicker sections. Most studies were performed using between 40 and 80 mAs. It is estimated that the patients' radiation exposure was 20% that of conventional high resolution CT (HRCT) and 57% that of routine chest CT. Diagnostic HRCT scans can be obtained in infants and young children without the need for suspended respiration or specialized ultrafast CT scanners. PMID- 8008502 TI - Portal cavernoma in congenital hepatic fibrosis. Angiographic reports of 10 pediatric cases. AB - A retrospective pediatric study of 30 angiograms in congenital hepatic fibrosis (CHF) was undertaken to analyze the different aspects of the portal venous system in this disease. Besides the classical angiographic signs (hepatofugal veins and intrahepatic duplications), a hepatopetal venous network was present in ten children, contrasting with the patency of the portal venous system. Analysis of the medical charts for these ten patients showed that the clinical signs and outcome were similar to classical CHF. Liver biopsies were available in six cases and, in addition to the diagnostic features of CHF, demonstrated paucity or absence of portal venules. This unusual association of hepatopetal and hepatofugal collateral veins in an intrahepatic block could be explained by hypoplasia or thrombosis of portal venules. Thus, the association between hepatomegaly and hepatopetal collateral veins without portal obstruction should be suggestive of CHF. PMID- 8008503 TI - Neurofibromatosis type 1 involving the liver: ultrasound and CT manifestations. AB - We present a rare case of neurofibromatosis type 1 (NF-1) involving the liver in a 15-year-old girl. Abdominal ultrasonography revealed infiltrative hypoechoic masses around the porta hepatitis and intrahepatic portal branches. CT also revealed extensive low-attenuation masses in the hepatic hilum and retroperitoneum. The tumor spread into the liver along the portal vein. It should be borne in mind that the liver may be involved by neurofibromas in patients with NF-1. PMID- 8008504 TI - Hypomelanosis of Ito: MR findings. AB - We present a patient with hypomelanosis of Ito who showed extensive white matter lesions on brain MRI. The finding of no apparent demarcation between gray and white matter may indicate a neuronal migration disorder. PMID- 8008505 TI - A right lower abdominal mass due to Yersinia mesenteric lymphadenitis. AB - We report the case of a 14-year-old female with Yersinia mesenteric lymphadenitis presenting as a right lower abdominal mass. Although such cases are very rare, Yersinia infection should be considered in the differential diagnosis of a right lower abdominal mass. PMID- 8008506 TI - Bilateral osteomyelitis due to intraosseous infusion: case report and review of the English-language literature. AB - Intraosseous infusion, a mode of peripheral access largely abandoned in the 1940s and 1950s, is becoming increasingly popular in the setting of pediatric crisis. While complications are rare when the procedure is properly performed, the risk of osteomyelitis increases with prolonged infusions. We present a case of bilateral osteomyelitis secondary to intraosseous infusion. PMID- 8008507 TI - Varus deformity of the distal end of the femur secondary to a focal fibrous lesion. AB - Severe unilateral varus deformity of the distal end of the femur secondary to a focal fibrous lesion is reported. It is a malformative process rare at this level, this being the first report of it in the radiological literature. The conventional radiograph is pathognomonic and CT is useful in the confirmation of the fibrous tissue. Osteotomy is indicated only if the deformity progresses or the angle of varus is severe. PMID- 8008508 TI - A functioning double aortic arch in an infant: a case report. AB - A case of a functioning double aortic arch is presented in a 4-month-old boy with recurrent respiratory infections and poor feeding. An esophagogram, Doppler echocardiography and aortography were performed. We describe the typical findings of this rare disorder. PMID- 8008509 TI - Hepatic spindle cell tumors in HIV positive children. AB - Spindle cell tumors (leiomyoma, leiomyosarcoma) have been described in HIV infected children involving the gastrointestinal tract, respiratory tract and liver. The same tumor has been reported in immunocompromised children following liver and renal transplantation. A case of hepatic spindle cell tumor in an HIV infected child is discussed. PMID- 8008510 TI - Congenital broncho-oesophageal fistula in childhood. PMID- 8008511 TI - Clinical features, diagnosis, and treatment of tuberculosis in infants. AB - OBJECTIVE: Despite the recent resurgence of tuberculosis among children in the United States, no series of infants < 1 year of age with tuberculosis has been reported in the last 20 years. This study was undertaken to describe the epidemiology, clinical, and radiographic manifestations, and response to therapy in infants < 1 year of age with tuberculous disease. METHODS: The medical records were reviewed for all infants age 12 months or less with a diagnosis of tuberculosis and cared for at the Children's Tuberculosis Clinic at Ben Taub General Hospital in Houston, Texas between January 1, 1985 and June 30, 1992. RESULTS: Of the 47 infants identified, 51% were female. The median age at diagnosis was 8 months (range 3.5 to 12 months). Fifty-one percent of the infants were African-American and over one-third were Hispanic. All patients were born in the United States. Diagnosis resulted from the examination of an ill infant in 79% of cases, a case contact investigation of an adult suspected of having tuberculosis in 19%, and routine tuberculin skin testing in 2%. An adult with infectious tuberculosis who had contact with the infant was identified in 68% of cases. Intrathoracic disease alone was present in 70% of cases. Fourteen (30%) infants had extrapulmonary tuberculosis (11 central nervous system disease, 2 disseminated disease, and 1 cervical adenitis). Gastric aspirate cultures yielded Mycobacterium tuberculosis from 75% of the infants with isolated intrathoracic disease. Forty-five infants successfully completed therapy and only one death was directly related to tuberculosis. Forty-eight percent of the infants with pulmonary tuberculosis were treated with a 6-month regimen consisting of isoniazid and rifampin supplemented during the first 2 months by pyrazinamide. Eighteen infants received some twice weekly directly observed therapy mainly due to documented or suspected nonadherence. Treatment was well-tolerated; one patient (2%) developed hepatotoxicity due to isoniazid. No infant had a relapse or recurrence of disease in 6 months to 7 years follow-up for a median of 3 years (range, 6 months to 7 years). CONCLUSION: Most infants with tuberculosis are symptomatic at the time of diagnosis, and bacteriologic confirmation was obtained in 70% of cases. A contact investigation of the household should be initiated immediately when an infant is suspected of having tuberculosis because valuable information needed to establish the diagnosis and guide therapy in the infant may be obtained. Intensive 6-month and twice weekly directly observed therapy appear to be well-tolerated and effective for the treatment of pulmonary tuberculosis in infants. PMID- 8008513 TI - Infant sleep position and sudden infant death syndrome risk: a time for change. PMID- 8008512 TI - The prone alternative. PMID- 8008514 TI - Role of panic attacks in the intractability of asthma in children. PMID- 8008515 TI - Senior-Loken syndrome: revisited. PMID- 8008516 TI - Treatment of a Jehovah's Witness with immune globulin: case of a child with Kawasaki syndrome. PMID- 8008517 TI - Unexpected death due to acute airway obstruction in daycare centers. PMID- 8008518 TI - Multiple Africanized bee stings in a child. PMID- 8008519 TI - The pediatrician's role in helping children and families deal with separation and divorce. Committee on Psychosocial Aspects of Child and Family Health. American Academy of Pediatrics. PMID- 8008520 TI - PCBs in breast milk. Committee on Environmental Health. American Academy of Pediatrics. PMID- 8008521 TI - Distinguishing sudden infant death syndrome from child abuse fatalities. Committee on Child Abuse and Neglect. American Academy of Pediatrics. PMID- 8008522 TI - Camphor revisited: focus on toxicity. Committee on Drugs. American Academy of Pediatrics. PMID- 8008523 TI - Metered-dose inhalers for young athletes with exercise-induced asthma. Committee on Sports Medicine and Fitness. American Academy of Pediatrics. PMID- 8008524 TI - Utilization of prenatal diagnosis for cystic fibrosis over the past seven years. AB - OBJECTIVE: First trimester prenatal diagnosis (PD) by DNA analysis for cystic fibrosis (CF) has been available for parents of affected children since May 1986. METHODS: In a prospective study 37 couples with a single child affected by CF were investigated. Fathers and mothers were interviewed simultaneously, and their attitudes towards further childbearing and potential utilization of PD ascertained. Parental answers were treated as one. A 7-year follow-up allowed comparison between intended and actual behavior. RESULTS: At the time of the interview, 16 parents (43%) were determined to have further children. Nineteen parents (51%) said they would certainly or probably utilize PD in case of pregnancy. Their predominant reason for favoring PD was the strong desire to have a healthy child (47%). Among the 18 rejectors (49%) the fear of an unsolvable conflict in case of an affected fetus prevailed (39%). Twenty-four pregnancies actually occurred in 18 families. Utilization of PD was arranged in five (21%) and finally performed in four (17%) cases. CONCLUSION: Availability of PD does not substantially change the reproductive behavior of parents of children with CF. Reasons for this were multifactorial, with anticipated difficulty in deciding to continue or terminate pregnancy being predominant. PMID- 8008525 TI - Recommended schedule for immunization of healthy infants and children. Committee on Infectious Diseases. American Academy of Pediatrics. PMID- 8008527 TI - Who do you want to care for your sick newborn? PMID- 8008526 TI - Concerned about ribavirin recommendations. PMID- 8008528 TI - Who do you want to care for your sick newborn? PMID- 8008529 TI - Nitric oxide and bleeding time. PMID- 8008530 TI - Glucocorticoid-responsive hypotension in extremely low birth weight newborns. PMID- 8008531 TI - Children's memory for a salient medical procedure: implications for testimony. AB - OBJECTIVE: Protecting sexually abused children hinges on their ability to remember and report events surrounding alleged incidents of abuse. This study was designed to provide information on young children's memory and recall of stressful experiences. METHODOLOGY: Children's memory for features of a voiding cystourethrogram (VCUG) experience were examined because this invasive procedure is similar in many respects to incidents of sexual abuse. The recall performance of 24 3- to 7-year-olds was assessed immediately after the VCUG and after a delay of 6 weeks using a hierarchically structured interview protocol including both open-ended and more specific questions. To assess correlations between recall performance and distress, behavioral and physiological indicators of distress were measured during the procedure. RESULTS: The children remembered 88% of the component features of the VCUG experience at the initial assessment and 83% after 6 weeks. Behavioral and salivary cortisol measures indicated that the children were distressed during the procedure. Although several of the behavioral measures were correlated negatively with the amount of recall, levels of salivary cortisol did not predict the children's recall performance. CONCLUSION: The findings suggest that, under some conditions, young children can provide accurate and detailed reports of personally experienced distressful events. PMID- 8008532 TI - The incidence of prenatal syphilis at the Boston City Hospital: a comparison across four decades. AB - OBJECTIVE: To examine the incidence and epidemiologic correlates of congenital syphilis at an inner-city Boston hospital, and draw comparisons with the situation at the same hospital 40 years ago. DESIGN: Chart review and comparison with data collected in 1951. SETTING: Maternity and pediatric services at Boston City Hospital. METHODS: A study conducted in 1951 on the maternity service of Boston City Hospital in which demographic data were collected on all women admitted in labor over a 5-month period was replicated. Serologic testing for syphilis was carried out on these women, and the demographic and medical correlates of positive maternal syphilis serology were examined. This study was repeated exactly 40 years later, using the cord blood screening for syphilis done routinely at delivery and a review of prenatal records. RESULTS: From a group made up largely of married white women in 1951, the study population shifted in 1991 to a group made up mostly of minority women, with 75% unmarried. In 1951, 24 patients were diagnosed with syphilis either before or during the pregnancy, giving a prevalence rate of 2.4%. In 1991, 25 of 647 women were diagnosed with syphilis, for a prevalence rate of 3.9%. The women with positive cord blood serologies had a higher rate of other sexually transmitted diseases and substance abuse. No symptomatic cases of congenital syphilis were seen in 1951 or in 1991, although at least 11 of the 26 infants born to mothers with positive serologies in 1991 received intravenous penicillin therapy. CONCLUSIONS: The continued prevalence of diagnosed syphilis in women at delivery reflects an inner-city epidemic of congenital syphilis that is tied to substance abuse, human immunodeficiency virus, and changing social patterns, as well to older problems of serologic screening, prenatal care, treatment failures, and maternal reinfection. It is essential that screening programs be maintained and improved in this high-risk population, and that infants born to mothers with positive serologies receive full and adequate treatment if there is any doubt at all about their infection status. PMID- 8008533 TI - Simethicone in the treatment of infant colic: a randomized, placebo-controlled, multicenter trial. AB - OBJECTIVE: To determine the efficacy of simethicone in the treatment of infant colic. DESIGN: Randomized, double blind, placebo-controlled. SETTING: Three general pediatric practices in distinct geographic regions. PATIENTS: Eighty three infants between 2 and 8 weeks of age with infant colic. INTERVENTIONS: Treatment with simethicone and placebo in double blind crossover fashion. RESULTS: A total of 166 treatment periods, ranging from 3 to 10 days, were evaluated in the 83 infants. Compared to baseline, improvement in symptoms was reported for 54% of the treatment periods, worsening was reported for 22%, and, for 24%, there was no change. The likelihood of the treatment period being rated as showing improvement, worsening, or no change was the same whether the infant was receiving placebo or simethicone. Twenty-eight percent of he infants responded only to simethicone, 37% only to placebo, and 20% responded to both. No statistically significant differences were noted among these three groups of responders. No difference could be shown even when infants with "gas-related symptoms" (by parental report) were separated out as a group. CONCLUSION: Although both produced perceived improvements in symptoms, simethicone is no more effective than placebo in the treatment of infantile colic. PMID- 8008534 TI - A 20-year population-based study of postdiarrheal hemolytic uremic syndrome in Utah. AB - OBJECTIVE: To determine epidemiologic features, trends in frequency, and predictors of clinical outcome of postdiarrheal hemolytic uremic syndrome (HUS) in Utah. DESIGN: A 20-year population-based study of HUS with a review of the HUS registry, hospital records, transplant registry, and a survey of pediatricians and pediatric nephrologists to ensure completeness of ascertainment. POPULATION: All Utah residents under 18 years of age with HUS occurring after a diarrheal prodrome between 1971 and 1990. OUTCOME MEASURES: Incidence of HUS, severity, complications, and long-term sequelae. RESULTS: There were 157 cases during 20 years; 140 (89%) occurred after a diarrheal prodrome. The mean annual incidence was 1.42/100,000 children (range 0.2 to 3.4/100,000 children/year). Periods of high incidence occurred; however, there was no overall sustained increase in incidence. Escherichia coli O157:H7 was isolated from the stool of 62% of children who had specimens submitted. There were no differences between the first and second decade in the proportion with diarrheal prodrome, bloody diarrhea, most abnormal laboratory values, hospital course, or outcome. However, admission laboratory abnormalities were more severe during the first decade suggesting a delay in diagnosis. Age < 2 years, anuria before admission, and higher white blood cell counts on admission predicted severe disease. Bad outcome (death, end stage renal disease, or stroke) occurred in 11%; 5% died. Chronic renal sequelae, usually mild, were found on follow-up (median 6.5 years) in 51% of survivors. CONCLUSIONS: HUS has been an important clinical and public health problem in Utah for 20 years. The consistency of the clinical and epidemiologic features over 2 decades suggests that a common etiologic agent has accounted for most cases of HUS in this region since 1971. PMID- 8008535 TI - Are children at risk for sexual abuse by homosexuals? AB - OBJECTIVE: To determine if recognizably homosexual adults are frequently accused of the sexual molestation of children. DESIGN: Chart review of medical records of children evaluated for sexual abuse. SETTING: Child sexual abuse clinic at a regional children's hospital. PATIENTS: Patients were 352 children (276 girls and 76 boys) referred to a subspecialty clinic for the evaluation of suspected child sexual abuse. Mean age was 6.1 years (range, 7 months to 17 years). DATA COLLECTED: Charts were reviewed to determine the relationships of the children to the alleged offender, the sex of the offender, and whether or not the alleged offender was reported to be gay, lesbian, or bisexual. RESULTS: Abuse was ruled out in 35 cases. Seventy-four children were allegedly abused by other children and teenagers less than 18 years old. In 9 cases, an offender could not be identified. In the remaining 269 cases, two offenders were identified as being gay or lesbian. In 82% of cases (222/269), the alleged offender was a heterosexual partner of a close relative of the child. Using the data from our study, the 95% confidence limits, of the risk children would identify recognizably homosexual adults as the potential abuser, are from 0% to 3.1%. These limits are within current estimates of the prevalence of homosexuality in the general community. CONCLUSIONS: The children in the group studied were unlikely to have been molested by identifiably gay or lesbian people. PMID- 8008536 TI - Sexual politics and child protection: they don't mix. PMID- 8008537 TI - Ultrasound screening for developmental dysplasia of the hip in the neonate: the effect on treatment rate and prevalence of late cases. AB - OBJECTIVE: To assess the effect of ultrasound screening on primary diagnosis, management, and prevalence of late cases of developmental dysplasia of the hip (DDH). DESIGN: A randomized, controlled trial, including 11,925 newborn infants who were allocated to receive either general, or selective or no ultrasound screening in addition to the clinical examination. In the selectivity screened group only infants with risk factors or clinical findings of DDH received an ultrasound examination. The infants were at least 27 months old at the conclusion of the study. Those with risk factors for DDH had a radiograph examination of the hips at 4.5 months of age. RESULTS: The three study groups did not differ in terms of sex distribution or positive Barlow/Ortolani tests. General ultrasound screening resulted in a higher treatment rate than in either the selective or in the no ultrasound screening groups (3.4% vs 2.0% and 1.8%, P < .0001). For infants not subjected to treatment, ultrasound screening resulted in a higher follow-up rate because of nonconclusive early findings (13%, 1.8%, 0%, respectively; P < .0001). The prevalence of late subluxation or dislocation was lower for subjects assigned to general ultrasound screening than for those subjected to selective or no ultrasound screening, but the differences were not statistically significant (0.3, 0.7, 1.3 per 1000, respectively; P = .11, test for trend). CONCLUSION: The effect of ultrasound screening in reducing the prevalence of late DDH was at best marginal despite a considerable increase in diagnostic and therapeutic efforts. PMID- 8008538 TI - Immunization coverage and its relationship to preventive health care visits among inner-city children in Baltimore. AB - OBJECTIVE: To provide empirical data on immunization coverage and the receipt of preventive health care to inform policy makers' efforts to improve childhood immunization. DESIGN AND METHODS: We surveyed a random sample drawn from a birth cohort of 557 2-year-old children living in the inner-city of Baltimore. Complete information on all their preventive health care visits and immunization status was obtained from medical record audits of their health care providers. MAIN OUTCOME MEASURES: Age-appropriate immunizations and preventive health care visits. RESULTS: By 3 months of age, nearly 80% made an age-appropriate preventive health visit, but by 7 months of age, less than 40% had a preventive visit that was age-appropriate. In the second year of life, 75% made a preventive health visit between their 12- and 17-month birthdays. The corresponding age appropriate immunization levels were 71% for DTP1, 39% for DTP3, and 53% for measles-mumps-rubella vaccine. Infants who received their DTP1 on-time were twice as likely to be up-to-date by 24 months of age. CONCLUSIONS: Our analyses focus attention on the performance of the primary health care system, especially during the first 6 months of life. Many young infants are underimmunized despite having age-appropriate preventive visits, health insurance coverage through Medicaid, and providers who receive free vaccine from public agencies. Measles vaccination coverage could be improved by initiating measles-mumps-rubella vaccine vaccination, routinely, at 12 months among high risk populations. PMID- 8008539 TI - Rural-urban blood lead differences in North Carolina children. AB - OBJECTIVE: To examine the prevalence of and risk factors for having a blood lead elevation among young children in a predominantly rural state. METHODS: 20,720 North Carolina children at least 6 months and < 6 years of age were screened between November 1, 1992 and April 30, 1993 using either capillary or venous measurements of blood lead. Children were tested through routine screening programs that target low-income families and, hence, were not randomly selected. Eighty-one percent of the children were screened through local public health departments, and 19% were tested at private clinics. RESULTS: The estimated prevalences of having an elevated blood lead level among those tested were: 20.2% (> or = 10 micrograms/dL), 3.2% (> or = 15 micrograms/dL), and 1.1% (> or = 20 micrograms/dL). Black children were at substantially increased risk of having a blood lead > or = 15 micrograms/dL (odds ratio (OR) = 2.1, 95% confidence interval (CI) = 1.7 to 2.5). Children aged 2 years old had an elevated risk (OR = 1.4, 95% CI = 1.1 to 1.7) compared to 1-year-olds, and males were at slightly increased risk (OR = 1.2, 95% CI = 1.0 to 1.4). Living in a rural county was nearly as strong a risk factor as race (OR = 1.9, 95% CI = 1.6 to 2.4). The effect of rural residence was even greater among certain subgroups of children already at highest risk of having an elevated blood lead. The type of clinic (public vs private) where a child was screened was not associated with blood lead outcome. These same trends were seen for children with blood lead levels > or = 20 micrograms/dL. CONCLUSIONS: Among children screened from rural communities, the prevalence of elevated blood lead is surprisingly high. Though few physicians have embraced universal lead screening, these data support the need for greater awareness of lead exposure in children living outside of inner-cities. PMID- 8008541 TI - A randomized trial of a nursing intervention to promote the adjustment of children with chronic physical disorders. AB - OBJECTIVE: This study was conducted to determine whether a specialized form of nursing could help prevent or reduce psychosocial maladjustment among children, aged 4 to 16 years, with chronic physical disorders. In contrast to other studies, nurses were chosen to provide the intervention based on their central role in health care and the appropriateness of their training for this task. METHODOLOGY: A clinical trial was conducted in which 332 children and their families were randomly assigned either to receive this specialized nursing for a 1-year period, or to remain in the control condition. The children were all active outpatients in nine clinics at the Montreal Children's Hospital. Three measures of psychosocial functioning administered before and after the intervention were the basis for assessing its efficacy. The measures included the behavior problems profile of the Achenbach Child Behavior Checklist, the Personal Adjustment and Role Skills, completed by the parents, and two versions of the Self-Perception Profile (Harter) for children aged 4 to 7 years and 8 to 16 years. RESULTS: Differences between groups were examined both categorically and quantitatively. In the former, the percent of children with clinical scores (those above or below a cut-off indicative of maladjustment) at baseline and postintervention were compared. In the latter, the mean scores at the end of the trial were analyzed using analysis of covariance with the baseline scores as covariates. Statistically significant positive differences were found in the domain of anxiety/depression on the Personal Adjustment and Role Skills, and in the areas of scholastic competence, behavior, and global self-worth on the Harter. CONCLUSION: The results indicate that this intervention helps children with chronic disorders by preventing or reducing maladjustment. Most university prepared nurses already have the basic skills required to achieve these results; only a modest investment in reorientation may be needed. Thus, other pediatric centers should be able to replicate these findings and thereby take a major step toward improving the lives of children with chronic disorders. PMID- 8008540 TI - Goat's milk as a substitute for cow's milk in undernourished children: a randomized double-blind clinical trial. AB - OBJECTIVE: This paper compares the effects of goat's milk and cow's milk on weight gain and fat absorption, in children with overt malnutrition. METHODS: Thirty hospitalized malnourished children aged from 1 to 5 years were included in a randomized double-blind trial. The children were fed either goat or cow's milk with a randomized will defined composition, added with vegetable oil, sugar, vitamins and minerals o achieve 1,000 kcal/liter. Children were offered 100 kcal/kg on the first day, with a regular daily increase in energy intake thereafter that reached 200 kcal/kg per day on the tenth day. RESULTS: Both groups of children had the same degree of malnutrition on inclusion. The mean weight-for-height Z score was -1.7 in both groups. One death with candidiasis occurred in the goat's milk group. Weight gain was similar in both groups: 8.5 g/kg/day (SE = 1.37) with goat's milk and 7.8 (SE = 1.9) with cow's milk. There was no significant difference in HEM intake: 157 ml/kg/day (SE = 4), vs 162 (SE = 4) for goat and cow's milk, respectively. Fat absorption coefficients on the 15th day of treatment were also similar in both groups. CONCLUSION: These results suggest that goat's milk has a nutritional value similar to that of cow's milk and could be used as an alternative to cow's milk for rehabilitating undernourished children. PMID- 8008542 TI - Revised reference ranges for circulating neutrophils in very-low-birth-weight neonates. AB - OBJECTIVE: Healthy very-low-birth-weight neonates (VLBW, < or = 1500 g) exhibit a high incidence of neutropenia according to Manroe's reference ranges for neutrophil indices. Since these reference ranges may be inappropriate for VLBW neonates, we determined the reference ranges for circulating peripheral neutrophils in VLBW neonates between birth and 28 days of age. METHODS: Serial, timed peripheral white blood cell counts (n = 1788) were prospectively obtained between birth and 28 days from 193 inborn, VLBW neonates delivered between January 1 and December 31, 1990. Data were divided into neutrophil counts obtained prior to (n = 630) and after (n = 1158) 60 hours of age. After excluding counts from neonates with perinatal and/or neonatal complications, values from "normal" neonates were compared to Manroe's reference ranges. Where indicated new ranges were developed. RESULTS: Although immature neutrophil (ATI) and immature:total neutrophil (I:T) values were within Manroe's reference ranges (P > .1) throughout the neonatal period, 67% of total neutrophil values (ATN) obtained prior to 60 hours of age were outside (P < .001) and 95% were considered neutropenic. Newly developed ATN reference ranges for VLBW neonates have a wider range of distribution compared to Manroe's results, primarily reflecting a decrease in the lower boundary. ATN values between 61 hours and 28 days also differed (P < .001), and new ranges had upper and lower boundaries of 6000 and 1100/mm3, respectively. Maternal hypertension was associated with neonatal neutropenia (P < .001) without abnormalities of ATI or I:T prior to day 3 of life; however, neutrophilia predominated after day 7. Between birth and 28 days > 70% of ATN values were abnormal in neonates with apnea, neutrophilia occurring in > 90% of counts; I:T values, however, were normal between 61 hours and 28 days. CONCLUSIONS: Normal preterm VLBW neonates have ATN reference ranges that differ significantly from that for larger, older neonates, demonstrating the effects of development on neutrophil dynamics. The predictability of neonatal infection using these new reference ranges requires additional study. PMID- 8008543 TI - Pediatric resident attitudes about technologic support of vegetative patients and the effects of parental input--a longitudinal study. AB - OBJECTIVE: To evaluate the change over time of attitudes about withdrawal of care from hopelessly ill children among a cohort of pediatric residents. DESIGN: Prospective data collection via surveys. SETTING: A pediatric residency program in a children's hospital. SUBJECTS: Pediatric residents beginning training in 1987 and 1988; 29 residents completed the study. INTERVENTIONS: Study participants completed a structured case-oriented questionnaire yearly from June 1988 through the completion of their residency training. The withholding of vasoactive agents or cardiopulmonary resuscitation, and the withdrawal of intravenous fluids, nutrition, or mechanical ventilation were the specific therapeutic options presented for a patient in a persistent vegetative state. The effects of time (further training) and parental wishes on resident decisions were assessed. MEASUREMENTS AND MAIN RESULTS: No resident wanted to provide intensive care to a child in a persistent vegetative state who was in respiratory failure; all residents would withhold vasoactive agents and CPR from such a child. At the conclusion of training, most (97%) would withdraw mechanical ventilation. A minority would withdraw intravenous (IV) fluids (41%) or nutrition (35%). Residents became more willing to withdraw IV fluids from these patients (0/16 vs 6/16; P = .03) and to withhold or withdraw therapies in general (P = .03) over the course of their training. All of this change occurred over the first year of training. Parental wishes altered treatment plans for these patients significantly, both when parents desired additional treatment (P < .0001), and when parents wanted treatment stopped (P = .04). The residents' level of training had no effect on responses to parents' therapeutic requests. CONCLUSION: Although exposure to level of care issues occurs throughout pediatric residency training, almost all changes in trainees' attitudes occur during the first year. Efforts to promote effective learning and coping should be concentrated in this period. PMID- 8008544 TI - Pediatric subspecialty training, certification, and practice: who's doing what. AB - OBJECTIVE: To examine the extent of pediatric subspecialty training, certification, and practice among general and subspecialty pediatricians and to determine how the diversity of pediatric careers may affect physician workforce supply estimates. METHOD: A sample of 4,000 self-designated pediatricians and pediatric subspecialists from the American Medical Association's Physician Masterfile were surveyed in 1991 by the American Academy of Pediatrics. Seventy six percent of the sample responded to the 6-page questionnaire on practice characteristics, training, and demographic information. RESULTS: Two-thirds of pediatricians are not subspecialty trained (66.3%), 15.1% are certified subspecialists, 11.3% are trained but not subboard certified, and 7.3% are subspecialty trained in an area with no certification exam. Subspecialty training did not always predict subspecialty practice; 19% of pediatricians without subspecialty training spend some time in a subspecialty, and 13% of those who are subspecialty trained practice general pediatrics exclusively. Certified subspecialists and those who cannot as yet become certified are most likely to practice their subspecialty. One-fourth of those trained in a certifiable subspecialty but who remain uncertified practice general pediatrics exclusively. The proportion of direct patient care time spent overall, and the proportion of direct patient care time spent in the subspecialty are also related to subspecialty certification and training/practice consistency. CONCLUSION: Pediatric workforce supply projections should incorporate more than certification and training information in calculating estimates, as the practice of general and subspecialty pediatrics is very diverse and accommodating of integrative styles. PMID- 8008545 TI - Pediatric defibrillation: current flow is improved by using "adult" electrode paddles. AB - OBJECTIVE: Current flow, the major determinant of defibrillation success, depends on delivered energy and transthoracic impedance. Previous experimental data suggest that transthoracic impedance is higher using "pediatric" electrode paddles compared to the larger "adult" electrode paddles. There are few data from actual shocks to support the experimental studies. The purpose of this study was to measure transthoracic impedance during actual shock delivery and to determine the optimal electrode paddle size for pediatric defibrillation and cardioversion. METHODS: We prospectively evaluated all shocks of < or = 20 joules given to pediatric patients at the University of Iowa from 1988 to 1992. Data collected included energy selected by the operator, energy delivered by the defibrillator, peak current flow and transthoracic impedance. Data were analyzed by unpaired t test and linear regression. RESULTS: Fifty-five shocks were delivered to 20 patients, age newborn to 8 years. Thirty-seven shocks were given with "pediatric" electrode paddles (surface area 21 cm2) and 18 with "adult" electrode paddles (surface area 83 cm2). Selected energy correlated well with delivered energy (r = .98, P < .0001). Delivered energy using "pediatric" electrodes did not differ from that delivered with "adult" electrodes (8.0 +/- 0.9 joules vs 10.5 +/- 1.2 joules P > .1). However transthoracic impedance was significantly higher with "pediatric" electrodes (78.1 +/- 4.4 ohms vs 54.6 +/- 2.7 ohms P < .0008), resulting in lower peak current flow through "pediatric" electrode paddles (6.2 +/- 0.5 amps vs 8.7 +/- 0.5 amps P < .002). There was no correlation between joules/kg and peak current flow (r = .26, P > .05). CONCLUSION: Use of "pediatric" electrode paddles results in higher transthoracic impedance and thus lower peak current flow. In pediatric defibrillation, larger "adult" electrode paddles should be used as soon as chest size permits (approximately 10 kg). Lower transthoracic impedance results in higher current flow that facilitates cardioversion and defibrillation. PMID- 8008546 TI - Chronic organophosphate exposure associated with transient hypertonia in an infant. AB - OBJECTIVE: A 12-week-old infant girl developed persistent hypertonicity of the extremities, and, at the age of 8 months, it was discovered that her home had been treated with an excessive application of the organophosphate insecticide diazinon 5 weeks prior to the onset of symptoms. An estimation of her daily diazinon dose and possible correlation with her disease was made. METHODS: Analyses were performed for residues of diazinon in the home and for metabolites of diazinon in the infant. The infant was removed from the home. RESULTS: Six months after application the remaining diazinon residue on the floor was 230 ng/cm2 vs 38 ng/cm2 expected immediately after a normal application. Vacuum cleaner dust contained 1700 parts per million of diazinon. The air contained 2.8 ng/m3. The infant's urine contained 60 parts per billion of diethylphosphate and 20 parts per billion of diethylthiophosphate which calculates to a diazinon dose of approximately 0.02 mg/kg/d. When the infant was removed from the home, muscle tone returned to normal shortly thereafter. CONCLUSIONS: The evidence for an association between organophosphate exposure and the sole de-velopment of hypertonicity without other signs of intoxication in an infant is presented. Physicians should consider organophosphate insecticide exposure as a possible cause of hypertonicity in infants. PMID- 8008547 TI - Intensive care treatment decisions: the roots of our confusion. AB - BACKGROUND: Decisions to withdraw or withhold treatment from infants and children are continuing concerns. Physicians voice confusion over perceived legal requirements. This confusion may lead to overtreatment of patients. Recent evidence suggests legal concerns still shape physician treatment decisions. OBJECTIVE: This study was undertaken to determine if the legal standard governing these medical decisions was clearly stated. DESIGN: Conventional legal research was performed. Because the 1984 Federal Child Abuse Amendments require these issues to be resolved by state laws, statues of the 50 states and the District of Columbia were reviewed to ascertain if they would support a charge of child abuse for the inappropriate withdrawal of life-support from a child. An electronic legal database was queried for all cases involving withdrawal of life-support in children since 1984; the cases were analyzed to determine if judges were applying the federal legal standard. RESULTS: Current child abuse reporting laws would support the federal standard in all 50 states and the District of Columbia. Six reported withdrawal cases were identified; none applied the federal standard. There is an emerging state legal standard that is flexible and subjective and allows a quality of life analysis because it is based on parental authority. This standard conflicts with the federal standard. CONCLUSIONS: The current law is unclear because two competing legal standards coexist; physicians cannot simultaneously meet both standards. Choosing to apply the state legal standard in clinical medical practice should support families in times of stress and relieve physicians of the burden of considering who is potentially overtreated. PMID- 8008548 TI - [Community pneumopathies in children: two principal clinical forms, one single consensus]. PMID- 8008549 TI - [Chlamydia pneumoniae: possibly, the third cause of epidemic bacterial pneumopathies?]. PMID- 8008550 TI - Overriding stimulus-driven attentional capture. AB - Theeuwes (1992) found a distracting effect of irrelevant-dimension singletons in a task involving search for a known target. He argued from this that selectivity is determined solely by stimulus salience; the parallel stage of visual processing cannot provide top-down guidance to the attentive stage sufficient to permit completely selective use of task-relevant information. We argue that in the task used by Theeuwes, subjects may have adopted the strategy of searching for an odd form even though the specific target form was known. In Experiment 1, we replicated Theeuwes's findings. Search for a circle target among diamond nontargets was disrupted by the presence of a diamond nontarget that was uniquely colored. In two subsequent experiments, we discouraged the singleton detection strategy, forcing subjects to search for the target feature. There was no distracting effect of a color singleton in these experiments, even with displays physically identical to those of Experiment 1, demonstrating that top-down selectivity is indeed possible during visual search. We conclude that goal directed selection of a specific known featural identity may override stimulus driven capture by salient featural singletons. PMID- 8008551 TI - Phonological codes are early sources of constraint in visual semantic categorization. AB - Two experiments were directed at early phonological activation in the semantic categorization task. In Experiment 1, briefly exposed targets homophonic to category exemplars (ROWS for the category A FLOWER), and their graphemic controls (ROBS), were judged for category membership with and without a backward pattern mask. False positives were greater for ROWS than ROBS to the same degree under both unmasked and masked conditions. In Experiment 2, false positives were examined in the semantic categorization task under backward dichoptic masking by pseudowords that were, in turn, masked monoptically by a pattern mask. Briefly exposed homophones (e.g., WEAK), masked by a phonologically similar pseudoword ("feek"), a graphemic control ("felk"), or an unrelated pseudoword ("furt"), were categorized as category exemplars (A UNIT OF TIME). The difference in false positives was significant for WEAK-feek versus WEAK-furt, but not for WEAK-felk versus WEAK-furt. It was suggested that the persistence of the homophonic effects under the pattern masking of Experiment 1 and their amplification under the phonological masking of Experiment 2 were because phonological codes cohere rapidly and provide, thereby, immediately available constraints on semantic processing. PMID- 8008552 TI - Modifications of the Poggendorff effect as a function of random dot textures between the verticals. AB - In the present research, we investigated the modification of the strength of the Poggendorff illusion as a function of different densities of random dot textures filling the space between the verticals. The results of Experiment 1 show that the illusory effect is a nonlinear function of the texture parameter r, the ratio of black pixels to white and black pixels, with a minimum for r = 0.5, approximately, and a maximum for r = 0 and r = 1. The results may be interpreted by an analytical model of perceptual space dynamics, in which the effect depends on the amount of interaction between points of different light intensity. A computer simulation performed by applying the analytical model to different values of r shows a good agreement between the predictions and the experimental data. To test the hypothesis underlying the model, a second experiment was carried out to measure the magnitude of the expansion of the space between the verticals as a function of the parameter r. The results are consistent with the hypothesis of the model. The overall data are discussed in terms of their implications on various theories proposed for the Poggendorff illusion. PMID- 8008553 TI - Use of vocalic cues to consonant voicing and native language background: the influence of experimental design. AB - For native speakers of English and several other languages, preceding vocalic duration and F1 offset frequency are two of the cues that convey the stop consonant voicing distinction in word-final position. For speakers learning English as a second language, there are indications that use of vocalic duration, but not F1 offset frequency, may be hindered by a lack of experience with phonemic (i.e., lexical) vowel length (the "phonemic vowel length account": Crowther & Mann, 1992). In this study, native speakers of Arabic, a language that includes a phonemic vowel length distinction, were tested for their use of vocalic duration and F1 offset in production and perception of the English consonant-vowel-consonant forms pod and pot. The phonemic vowel length hypothesis predicts that Arabic speakers should use vocalic duration extensively in production and perception. On the contrary, Experiment 1 revealed that, consistent with Flege and Port's (1981) findings, they produced only slightly (but significantly) longer vocalic segments in their pod tokens. It further indicated that their productions showed a significant variation in F1 offset as a function of final stop voicing. Perceptual sensitivity to vocalic duration and F1 offset as voicing cues was tested in two experiments. In Experiment 2, we employed a factorial combination of these two cues and a finely spaced vocalic duration continuum. Arabic speakers did not appear to be very sensitive to vocalic duration, but they were about as sensitive as native English speakers to F1 offset frequency. In Experiment 3, we employed a one-dimensional continuum of more widely spaced stimuli that varied only vocalic duration. Arabic speakers showed native-English-like sensitivity to vocalic duration. An explanation based on the perceptual anchor theory of context coding (Braida et al., 1984; Macmillan, 1987; Macmillan, Braida, & Goldberg, 1987) and phoneme perception theory (Schouten & Van Hessen, 1992) is offered to reconcile the apparently contradictory perceptual findings. The explanation does not attribute native English-like voicing perception to the Arabic subjects. The findings in this study call for a modification of the phonemic vowel length hypothesis. PMID- 8008554 TI - The dynamics of the visual system in combining conflicting KDE and binocular stereopsis cues. AB - The dynamics of the visual system in combining multiple depth cues were investigated by measuring the temporal change in the perceived 3-D shape of a random-dot stimulus with conflicting kinetic depth effect (KDE) and binocular stereopsis cues. The KDE shape perception dominated for the first few seconds, and then was gradually supplanted by the stereo shape perception. The effects of various pre-adaptation stimuli suggested that the temporal change in the perceived shape resulted from a self-adaptation of the KDE mechanism that occurs mainly at the levels of motion and relative motion detection. PMID- 8008555 TI - Parallel processing of part-whole information in visual search tasks. AB - Combination of information from the parallel processing of different basic features (color, size, etc.) can be used to guide attention to targets defined by conjunctions of those features. Wolfe et al. (1990) argued that, although it was possible to guide attention to the conjunction of, for instance, color and orientation, it was not possible to guide attention to targets defined by conjunctions of two colors or two orientations. The present experiments demonstrate an exception to this rule. Although it is true that attention cannot be guided to a target that has red and green parts, attention can be guided to an item that can be described as a whole red target with a green part. In Experiments 1 and 2, we illustrate this point. In Experiments 3 and 4, we rule out some simple size-based accounts of this finding. In Experiments 5 and 6, we begin to explore the nature of these first steps toward dividing the visual scene into parts and wholes. PMID- 8008556 TI - Haptic perception of partial-rod lengths with the rod held stationary or wielded. AB - Three experiments on the haptic perception of partial-rod lengths are reported. The rods were gripped between the two ends and held horizontal. The subjects held the rods stationary; the distribution of mass of the segment in front of the hand was fixed, while the distribution of mass of the segment behind the hand was varied. Perceived forward length was found to be significantly affected by the distribution of mass of the backward segment. Similar results were obtained when the rods were wielded. The results indicated that partial-rod lengths are specified by functions of mechanical perturbations acting on the hand, and not by the breaking up of the first moment of mass or the moment of inertia of the rod by attention as suggested previously by others. The results are also discussed with respect to invariant detection and attention. PMID- 8008557 TI - Selective attention to global and local structure of objects: alternative measures of nontarget processing. AB - When individuals are asked to report either the global or the local level of structure in a stimulus pattern located inside a relevant object, distractors located within an irrelevant object will interfere only if they are at the same level of structure as that of the target item (Briand, 1993; Paquet & Merikle, 1988). The basis of this level-specific filtering is unclear, as is the true level of semantic analysis for the ignored items. In the present series of experiments, multiple measures of nontarget processing were used to assess concurrent interference, negative priming, and a category effect supposedly reflecting a more abstract level of semantic analysis. These different indicants were assessed in three experiments in which form, color, or a spatial precue was used to direct attention to the relevant stimulus pattern. Overall, cuing by form produced poorer spatial selectivity, whereas spatial precues and color led to better selectivity. However, the three measures of nontarget processing were not equally affected by these manipulations, with global information showing more evidence for semantic analysis than for local analysis regardless of the type of selection cue used. The results suggest that inhibition is not the basis of target selection when ignored items are local, but that it may be used when global items are ignored. PMID- 8008559 TI - Scholarships and loans for nursing education 1994-1995. PMID- 8008558 TI - Local and global factors of similarity in visual search. AB - Effects of the similarity between target and distractors in a visual search task were investigated in several experiments. Both familiar (numerals and letters) and unfamiliar (connected figures in a 5 x 5 matrix) stimuli were used. The observer had to report on the presence or absence of a target among a variable number of homogeneous distractors as fast and as accurately as possible. It was found that physical difference had the same clear effect on processing time for familiar and for unfamiliar stimuli: processing time decreased monotonically with increasing physical difference. Distractors unrelated to the target and those related to the target by a simple transformation (180 degrees rotation, horizontal or vertical reflection) were also compared, while the physical difference was kept constant. For familiar stimuli, transformational relatedness increased processing time in comparison with that for unrelated stimulus pairs. It was further shown in a scaling experiment that this effect could be accounted for by the amount of perceived similarity of the target-distractor pairs. For unfamiliar stimuli, transformational relatedness did have a smaller and less pronounced effect. Various comparable unrelated distractors resulted in a full range of processing times. Results from a similarity scaling experiment correlated well with the outcome of the experiments with unfamiliar stimuli. These results are interpreted in terms of an underlying continuum of perceived similarity as the basis of the speed of visual search, rather than a dichotomy of parallel versus serial processing. PMID- 8008561 TI - Super nurse or drudge? PMID- 8008560 TI - Professional development. Epilepsy: the role of the nurse (continuing education credit). PMID- 8008562 TI - Let's talk about sex. PMID- 8008563 TI - Rest and respiration during obstructive sleep apnoea. AB - Obstructive sleep apnoea (OSA) is a condition in which the airway is obstructed during sleep. Although often harmless, OSA can produce significant morbidity. This paper describes the condition and how it is assessed in a respiratory diseases unit. A case study is given that highlights the far-reaching physical, social and psychological sequelae to this condition. PMID- 8008564 TI - Sleep apnoea. Laser therapy for OSAS. AB - The standard treatments for obstructive sleep apnoea syndrome (OSAS) to date have been postural treatment, which involves the patient sleeping on the stomach; continuous positive airway pressure, using a nasal mask during the night to maintain a positive pressure to prevent collapse of the airway; and surgical uvolopalatopharyngoplasty (UPPP). This is a radical surgical procedure where the soft palate and uvula are excised. There are drawbacks to all of these procedures, either because patients may regard as unacceptable the position they must maintain in bed or the equipment required to be worn or because of surgical complications. This paper describes an alternative method of treatment that has shown good results and is less disturbing to the patient: laser resection of the palatopharynx. This procedure is relatively new to the UK and not as yet widely accepted by many doctors, although it has been performed on the continent for a number of years with documented results. PMID- 8008565 TI - Systems of life. Blood: 1. PMID- 8008566 TI - Information nurses need to tell patients about glaucoma. AB - The first paper in this series, which appeared on April 13, looked at some of the information patients and their families might want to know about stroke. This paper takes a look at how a physiologically much simpler subject might be handled. This series is not looking for the definitive guide to pathological conditions. It aims to draw on the expertise of nurses around the country to provide starting points or supplementary material for patient information guides that can be used in a variety of ways. Readers are invited to contribute. PMID- 8008567 TI - Arrhythmias associated with cardiopulmonary arrest. AB - This fourth paper in our resuscitation series looks at basic conduction of the heart and the electrocardiographic complexes involved. Life-threatening arrhythmias are discussed and guidelines for treatment given. PMID- 8008568 TI - Defining mental health? PMID- 8008569 TI - Disability aids. Moving people. PMID- 8008570 TI - People like us. PMID- 8008572 TI - Nurse education. Community revival. PMID- 8008571 TI - Nurse education. Lessons for all. PMID- 8008573 TI - Professional development. Epilepsy: revision notes (continuing education credit). PMID- 8008574 TI - Deals on meals. PMID- 8008575 TI - A fair hearing. PMID- 8008576 TI - Documentation and discharge planning for elderly patients. AB - This paper is based on data collected from 326 elderly patients recruited in the course of a descriptive study of discharge planning in eight acute medical and surgical wards of a large teaching hospital. Evidence suggested various areas with potential for improved documentation: particularly the need for more detailed recording of baseline information about physical and mental abilities; housing; community services used; and involvement of the carers on whom the elderly patients relied. The study highlights the need to obtain, early on, full and accurate information to facilitate timely and effective discharge planning. PMID- 8008577 TI - Improving discharge planning. AB - In ward 9 of the Nursing Development Unit at Whiteabbey Hospital, Newtonabbey, Northern Ireland, developments and innovations are channelled through the use of working groups which are essentially the pivot on which the unit rotates. This article details the activities of one of these groups, the discharge planning group. PMID- 8008578 TI - Resuscitation in special circumstances. AB - Basic and Advanced Life Support Guidelines should be followed as normal in cardiorespiratory arrest where there are 'special circumstances' such as near drowning, hypothermia, electrocution, poisoning, anaphylaxis and pregnancy. In order to increase the chances of a successful outcome there are specific considerations and actions that need to be taken. These will be discussed in this paper, the fifth in our resuscitation series. PMID- 8008581 TI - Classification of pressure sore severity. PMID- 8008580 TI - Developing health. Interview by Daloni Carlisle. PMID- 8008579 TI - New therapies for the treatment of genital warts. AB - The treatment of genital warts with cytodestructive agents such as podophyllin and trichloroacetic acid continues to impose a heavy burden on the workload of genitourinary medicine clinics. Consequently clinics are now looking to new, economical treatments that will improve the management of patients with genital warts. The most promising of these new agents is podophyllotoxin, which is now available in pharmaceutically pure form tailored for the home treatment of external genital warts in males and females. PMID- 8008582 TI - Male order. PMID- 8008583 TI - Mental health. Thin on the ground. PMID- 8008585 TI - Mental health. Encouraging collaboration. PMID- 8008584 TI - Mental health. A partnership for change. PMID- 8008586 TI - Mental health. Solid as a rock. Interview by Ian McMillan. PMID- 8008587 TI - Shift systems in England and Wales. PMID- 8008589 TI - Paradox in practice. PMID- 8008588 TI - Breathing space. PMID- 8008590 TI - Spotlight on a specialism. PMID- 8008591 TI - Seen but not heard. PMID- 8008592 TI - Body politic. Keep it confidential. PMID- 8008593 TI - Cancer: a special case. PMID- 8008594 TI - Demonstration sites for nurse prescribing. AB - Eight demonstration sites have been selected to show the value of nurse prescribing. This article explains the criteria used to select the sites and suggests ways in which community nurses can best prepare for the responsibilities of prescribing. PMID- 8008595 TI - Teaching nurses to prescribe. AB - Before nurses get their own prescription pads they must undertake the ENB validated education module. This article outlines the way this course will be run, as well as its content. PMID- 8008596 TI - Medical sales representatives. AB - This paper provides an overview of the legal and professional guidelines set out for medical sales representatives. It is hoped that the information will help nurses to manage their interactions with medical reps appropriately and in a way that is to their advantage. PMID- 8008597 TI - Older patients' experiences of discharge from hospital. AB - The second paper in a series describes the work of the Nursing Research Unit at the University of Edinburgh studying discharge planning for older patients going home from acute hospital care is described. Data were collected on the views and experiences of 326 patients aged 75 years and over and 117 of their carers. Ward sisters also completed questionnaires about ward structures and processes relating to discharge planning. Problems typical of those reported in previous similar studies were found. PMID- 8008598 TI - Paediatric basic life support--an update. AB - This paper highlights the need for health-care personnel to receive specific training in paediatric resuscitation. The aetiology of cardiopulmonary collapse in children, and the rationale behind the management of basic life support in this situation is outlined. PMID- 8008599 TI - Care before and after surgery for total hip replacement. AB - This paper provides a detailed account of the nursing care given to a 47-year-old man undergoing a total hip replacement. The pre- and post-operative period was uncomplicated and much of the information regarding nursing interventions can be considered as routine and can be applied to similar cases. PMID- 8008600 TI - HIV/AIDS--lessons from Zimbabwe. PMID- 8008601 TI - Client education. Just the ticket. PMID- 8008602 TI - X-ray vision of shorter queues. PMID- 8008603 TI - Infection control. Surgical glove perforation. PMID- 8008605 TI - Gulf nurses face enforced HIV tests to renew contracts. PMID- 8008604 TI - Infection control. Safe practice. PMID- 8008606 TI - Role of a nurse during emergency situation. PMID- 8008607 TI - Nursing scene in South Maharashtra: an overview. PMID- 8008608 TI - Dental insurance companies: partners or adversaries? PMID- 8008609 TI - Abrasion resistance of restorative glass-ionomer cements with a light-cured surface coating. AB - This is a comparative study of the Knoop hardness number and the toothbrush wear of a surface coating agent applied to the surface of a glass-ionomer restorative cement. A reduction in surface hardness of the coating agent resulted in an increase in brush wear. The light-cured glazing agent (Bellfeel Brightener) proved to be significantly harder than those coated with a light-cured bonding agent (Occlusin). Occlusin bonding agent was removed by comparatively rapid abrasion; however, the Bellfeel Brightener was significantly more resistant to such abrasion. The analysis of the surface hardness and scanning electron microscopy observations of the brushed surfaces of the samples suggested that Bellfeel Brightener was effective as a glazing material for glass-ionomer cement restorations. PMID- 8008610 TI - Efficacy testing of visible-light-curing units. AB - This study evaluated (1) the effect of known reductions in the output of curing lights on the depth of cure of various resins as determined by hardness measurements, and (2) the ability of the clinician to detect reduced light output by use of an explorer to compare the hardness of the top and bottom surfaces of resin specimens. Curing light output was reduced stepwise from 10 to 70% with neutral density filters. Hardness values indicated polymerization of the top surface to be generally unaffected by light blockage. Bottom surfaces were greatly affected: more with a 30-second than a 60-second cure time. Three clinicians utilized an explorer to compare the tops and bottoms of specimens of known hardness. Evaluators were unable to routinely detect differences of less than 20 to 30 Barcol numbers. The data indicate that a light meter is a more efficacious means of monitoring curing light performance than is a tactile test of resin surface hardness. PMID- 8008611 TI - Effect of distribution of resistance features in complex amalgam restorations. AB - This study measured fracture resistance of complex amalgam restorations when pins or amalgapins were either distributed around the preparation or concentrated in one area of the preparation. The occlusal surfaces of 80 extracted molars were ground flat to 2 mm occlusal to the cementoenamel junction (CEJ). Roots were notched and embedded. Teeth were sized and distributed equally into eight groups (n = 10). Resistance features, four TMS stainless steel Regular pins or four amalgapin channels, were inserted into each molar. Resistance features were either distributed at the four line angles of each molar or clustered at two line angles. Matrices were applied, and amalgam was mechanically condensed into the matrices. Restorations were adjusted to a 4 mm vertical height and flat occlusal surfaces. A load was applied to each restoration at either a 45 degrees or a 90 degrees angle to the long axis of the tooth. Distributed pins provided significantly more resistance than clustered pins in groups tested at 90 degrees. Resistance to fracture in all groups loaded at 45 degrees and in amalgapin groups was not significantly affected by distribution of resistance features. Pins provided significantly more resistance than amalgapins at both angles of testing. PMID- 8008612 TI - Microporous dentin zone beneath resin-impregnated layer. AB - The purpose of this study was to investigate marginal microleakage by examining the resin/dentin interface using a cryo-SEM and a silver ion penetration method. Class 5 cervical cavities were restored using an adhesive resin system following treatment with 37% phosphoric acid gel. The cavity wall adaptation was observed using cryo-SEM to avoid specimen damage. This observation showed excellent marginal adaptation of material to cavity walls and no gap formation. However, silver ions had penetrated beneath the resin-impregnated layer when observed with conventional SEM images, which showed the leakage of silver ions between the resin and decalcified tooth structure without gap formation. This study suggests that the bonding monomers of Clearfil Photo Bond were not fully able to penetrate into the demineralized dentin after phosphoric acid etching, thus leaving a porous zone as a microleakage pathway beneath the resin-impregnated layer. PMID- 8008613 TI - Histobacteriological analysis of acid red dye-stainable dentin found beneath intact amalgam restorations. AB - This study determined histologically the incidence of acid red dye-stainable dentin and its correlation to bacterial presence beneath intact clinically sound amalgam restorations. Fourteen of 16 clinically sound amalgam restorations (88%), serving an average of 11 years, had microscopically evident microorganisms in the subjacent dentin. Eleven of the 14 specimens containing bacteria (79%) exhibited acid red dye-stainable dentin. There was no obvious correlation between dye stainable dentin and the presence of bacteria on the walls of the cavity preparations studied. The question of how much dye-stainable dentin can be present beneath an amalgam restoration before the restoration fails is still unanswered. PMID- 8008614 TI - Mercury vapor release during insertion and removal of dental amalgam. AB - During a clinical simulation of insertion and removal of dental amalgams, mercury vapor levels increased slightly, but never exceeded the TLV of 0.05 mg/m3. The addition of indium to dental alloy did not affect the amount of mercury vapor released under these conditions. PMID- 8008615 TI - [Usefulness of doppler ultrasonography in diagnosing changes in atherosclerotic lesions in lower extremity arteries in hyperlipoproteinemia]. AB - The purpose of this study was to establish the correlation between the intensity of atherosclerosis of the lower extremities found in the course of the Doppler examination, and type of hyperlipoproteinaemia. An attempt was undertaken to analyse the relation of the risk factors of obliterative atherosclerosis to the condition of the arteries in the lower extremities. 53 men at the age of 37 to 63 years (mean age 51 years) were examined. HLP type IIa, IIb, IV, was found in 16, 19, 18 patients respectively. The control group consisted of 30 healthy non smoking men. The examination was performed using ACUSON 128 with a linear probe 5 and 7 MHz. The Doppler spectrum was registered from the external iliac, common femoral, superficial femoral, deep femoral and popliteal arteries. Simultaneously, a two-dimensional color picture of contrasted vessels, and the Doppler spectrum of blood velocity were recorded. Blood velocity spectrum was quantitatively assessed according to the classification suggested by Jager et al. The results of the Doppler examination confirmed the unfavourable influence of the so called risk factors on the progress of atherosclerosis, especially low serum concentration of HDL cholesterol and cigarette smoking. Besides, the examination has proved the possibility to diagnose even asymptomatic atherosclerotic lesions of the arteries of lower extremities. PMID- 8008616 TI - [Retrospective analysis of secondary failure of oral hypoglycemic drugs in patients with diabetes type II]. AB - The analysis of the incidence and risk factors of oral antidiabetic drugs secondary failure (sf) in type II diabetic patients was carried out in the study. The population of 1262 patients who felt into diabetes between 1980 and 1984 year from Zabrze area was analyzed retrospectively. The analysis was done in relation to 1989 year (after 10 year of the observation). In 194 (15%) of patients secondary failure was diagnosed. Sf appeared in 150 (17%) women and 44 (11%) men (p < 0.005). Multi factor analysis confirmed the higher susceptibility of females to the appearance of sf. Analysis also showed that significant risk factor of sf is the diagnosis of diabetes in 6th life decade in the patients with normal body mass. The percentage of sf varied between 5.1% and 19.5%. Performed analysis showed the higher sf incidence in female group and the influence of age at the moment of diagnosis in non obese patient son the appearance of sf. PMID- 8008617 TI - [Autoimmune hepatitis]. PMID- 8008618 TI - [Urodilatin--renal representative of the natriuretic family of peptides]. PMID- 8008619 TI - [Effect of urine alkalization on excretion of renal citrate and degree of urine saturation with calcium oxalate in patients with calcium-oxalate urolithiasis and in healthy subjects]. AB - The aim of the study was to compare the renal citrate excretion and the degree of urine saturation with calcium oxalate in patients with active calcium oxalate urolithiasis and in healthy subjects under basal conditions and after alkalization. There were 20 women before menopause with calcium stone disease aged 33.5 +/- 7.1 in the first group and 20 healthy women aged 32.3 +/- 7.6 in the second one. Sodium bicarbonate was administrated intravenously in a dose 16.8 g during 2 h. 24h excretion of calcium, magnesium and citrate, the degree of urine saturation with calcium oxalate and pH of urine before and after alkalization were evaluated. Hypocitraturia occurred in 45% of patients under basal conditions. The degree of urine saturation with calcium oxalate was significantly higher in women with nephrolithiasis (p < 0.01). A significant increase of citrate excretion (p < 0.001) and a decrease of calcium excretion (p < 0.05) after alkalization took place in both groups. The degree of urine saturation with calcium oxalate decreased significantly in patients with urolithiasis and in healthy subjects. During acute alkalosis, induced by sodium bicarbonate, increase of citrate excretion was observed in patients with urolithiasis in spite of hypocitraturia under basal conditions. This indicates that kidney function following alkalization is normal in "stone kidney". Significantly decreased saturation of urine with calcium oxalate was due to the decrease of calcium excretion and the increase of citrate excretion. In conclusion, the results show that the use of alkalizing factors in prevention of recurrent calcium urolithiasis is justifiable. PMID- 8008620 TI - [Level of endothelin-1 and 2 in plasma of patients with chronic renal failure]. AB - The aim of the study was to answer 3 questions: 1. does plasma endothelin level differ in patients with chronic renal failure from that of healthy subjects. 2. does plasma endothelin level differ in patients with chronic renal failure treated with haemodialysis from those treated without dialysis. 3. does plasma endothelin level change during haemodialysis. 63 patients with chronic renal failure (pnn, 23 treated without dialyses and 40 with dialyses) as well as 20 healthy subjects were studied. Plasma endothelin and creatinine were estimated under basal conditions and in the dialysed patients--immediately after dialysis. Plasma endothelin level was higher in patients with pnn than in normals, regardless to dialysotherapy. It rose after dialysis. Plasma creatinine fell after dialysis. Positive significant correlation was found between the levels of creatinine and endothelin in the whole group studied. PMID- 8008621 TI - [Influence of prolonged application of captopril upon pulmonary ventilation in patients with chronic congestive heart failure]. AB - Study was designed to investigate the effect of prolonged application of captopril on pulmonary ventilation in patients with chronic congestive heart failure (CCHF) without hypertension. Studies were carried out in 13 men aged 54 65 yrs with CCHF due to ischaemic heart disease. They were classified hemodynamically as III or IV stage according to the NYHA classification. Two periods of management were investigated. In the 1st period, lasting at least one month, cardiac glycosides, diuretics, nitrates, as well as diet and restricted physical activity were applied. In the 2nd period, lasting 21 days, additionally captopril was given in a daily dose of 2 x 12.5 or 2 x 25 mg depending on the drug tolerance. When the periods were terminated pulmonary ventilation was measured. The following indices were determined: FEF25, FEF50, FEF75, FEF25-75, FEV1, FVC,FEV1/FVC, SVC, FIVC, FIF25, FIF50, FIF75, FIF25-75. No significant effect of captopril upon pulmonary ventilation was found (p < 0.05). In any of the patients captopril-induced cough was not observed. It is concluded that prolonged management with captopril in patients with CCHF without hypertension has no disadvantageous influence upon pulmonary ventilation with exception of patients who are hypersensitive to the drug. PMID- 8008622 TI - [In-vitro study of anemia in chronic inflammatory conditions. Effect of recombined interleukin-1 beta on human erythropoiesis]. AB - Study was inspired by the suggestion that interleukin 1-beta (IL-1 beta), one of the major inflammatory mediators, is directly responsible for anaemia of chronic inflammatory conditions. Effect of IL-beta was studied in vitro on methyl cellulose cultures of normal human bone marrow cells, the inoculate having been previously highly enriched in progenitor and stem cells. Our data did not support results reported by others that IL-1 beta is a strong inhibitor of early stages of erythropoiesis in vitro measured by early and late BFU-E formation. About 30% statistically not significant CFU-E inhibition was observed. Above studies show that IL-1 beta role in the development of anaemia associated with chronic inflammatory diseases requires further studies. PMID- 8008623 TI - [D-Leu2]deltorphin, a 17 amino acid opioid peptide from the skin of the Brazilian hylid frog, Phyllomedusa burmeisteri. AB - A novel 17 amino acid peptide, having a D-leucine in position 2 of its sequence, has been isolated from methanol extracts of the skin of the Brazilian frog, Phyllomedusa burmeisteri. The sequence of the peptide is: Tyr-D-Leu-Phe-Ala-Asp Val-Ser-Thr-Ile-Gly-Asp-Phe-Phe-His-Ser-Ile-NH2. It displays a poor affinity for delta-opioid binding sites, both in the periphery and in the central nervous system. However, the shorter synthetic amidated analogue (1-10) possess both on the central and peripheral delta binding sites an agonistic potency equalling in affinity and exceeding in selectivity that of the enkephalins. The shorter amidated analogue (1-7) is virtually inactive on opioid binding sites in the periphery, but displays a clear-cut affinity for both delta and mu binding sites on rat brain membranes. To date six different D-amino acid residues have been found, always in position 2 of the sequence, in as many as 11 natural peptide molecules of animal origin. PMID- 8008624 TI - Differential modulation of invertebrate hemocyte motility by CRF, ACTH, and its fragments. AB - Various reports have shown that invertebrate hemocytes are responsive to mammalian neuropeptides and cytokines. In the present study, we demonstrate that corticotropin-releasing factor (CRF) and adrenocorticotropin (ACTH) fragments (1 24), (1-4), (4-9), (1-13), (1-17), and (11-24) significantly stimulate molluscan hemocyte migration, and the whole sequence (1-39) and the fragment (4-11) have an inhibitory effect. Differences between species were found with respect to the response to individual fragments. Additionally, the (4-11) fragment was able to antagonize some of the stimulatory fragments (4-9) as well as tumor necrosis factor (TNF-alpha)-induced chemotaxis. Our results suggest that invertebrate hemocytes are able to respond to CRF and ACTH fragments that in turn provide further evidence of the complexity of intercellular signaling within the immune system in relatively primitive animals. Thus, auto- and neuroimmunoregulatory activities in mammals must have had an earlier beginning than previously believed. PMID- 8008625 TI - Retroviral synthetic peptide serum antibodies in human sporadic amyotrophic lateral sclerosis. AB - We examined 101 sera from 32 adult sporadic amyotrophic lateral sclerosis (ALS) patients, including nine with positive enzyme-linked immunosorbent assay (ELISA) serum antibodies against human spuma retrovirus (HSRV) [human foamy virus (HFV)] envelope (env) and/or capsid (gag) proteins, for peptide seroreactivity. Synthetic peptides 10 to 14 amino acids in length were selected from HSRV (3), maedi-visna virus (1), human nerve growth factor-beta (1), and human amyloid-beta sequences (1). Eighteen of 101 ALS sera compared with six of 144 control sera reacted to any of the sequences (p < 0.01) (i.e., 8/32 ALS patients and 2/93 control patients bound to a synthetic peptide, p < 0.01). Peptide VLA- [NGF beta(1-14)] was reproducibly recognized by one of the 93 neurologic controls, and one of the 32 ALS patients reproducibly reacted to synthetic peptides [EET-, HSRVenv/NGF beta(55-61)] and [GSN-, beta-amyloid(25-35)] simultaneously. This amyloid-A(25-35) peptide corresponds to the neurotoxic and neurotrophic tachykinin homology sequence described by Yanker. Only ALS patients (no controls) reacted with the visna/CNTF peptide SMC- and HSRVbcl-1/amyloid(740-751) peptide EGP-. Testing a total of 245 sera from 125 patients, three reproducible reactivities (two ALS, one OND) were observed both with and without glutaraldehyde linkage. Of the four peptides recognized either by more than one serum from the same patient with ALS or by sera from ALS patients only (EET-, GSN , SMC-, EGP-), two share a circumscript homology with maedi-visna virus envelope glycoprotein (Table 1).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8008626 TI - The immunomodulatory activity of tetra- and tripeptides of tuftsin-kentsin group. AB - It was found that tuftsin (Thr-Lys-Pro-Arg) and its tetrapeptide analogues with the same amino acid composition, but different sequences, demonstrate immunosuppressive activity for the humoral, but not (excepting the Thr-Lys-Arg Pro tetrapeptide) for the cellular, immune response. The splitting of N-terminal residues from these tetrapeptides leads, however, to formation of tripeptides that are active in both humoral and cellular immune response tests. Thus, the biological degradation of peptides of the type investigated can seriously modulate their immunobiological activities. We also found that tetrapeptides Thr Arg-Lys-Pro and Thr-Lys-Arg-Pro, as well as tripeptides Arg-Lys-Pro and Lys-Arg Pro, distinctly differ in their immunomodulatory activities, although the structural differences consist in this case only in the displacement of two basic amino acid residues. PMID- 8008627 TI - Mild sustained effects of neonatal vasopressin and oxytocin treatment on brain growth and behavior of the rat. AB - The lasting effects of a 9-day neonatal exposure to vasopressin and oxytocin were examined in the rat to discover if peptide administration results in organizational effects. When tested in young adulthood, brain growth, not body growth, appeared to be impaired. Basal and challenge tests of urine production, carried out to see the development of the hormonal antidiuretic function of vasopressin, revealed no lasting changes, and therefore did not confirm earlier findings of an induced mild polyurea. Behavioral testing of learning by making use of a one-trail step-through paradigm with a 24-h retention trial--a test that is sensitive to vasopressin--did not show impairments. Open field tests, however, showed enhanced emotionality in the vasopressin-treated females, as well as an initially increased ambulation in the males, and increased grooming in both sexes, the latter also having been reported to be induced by vasopressin administration in the septal areas. Oxytocin treatment did not produce lasting changes. Our conclusion, therefore, is that peripherally circulating vasopressin can affect the organizational development of the rat brain. It remains to be established whether this is an effect obtained through changes in the general peripheral physiology or a reflection of plasticity phenomena at the level of central vasopressin neurotransmission. PMID- 8008628 TI - Effects of CLIP (corticotropin-like intermediate lobe peptide) and CLIP fragments on paradoxical sleep in rats. AB - The effects of the POMC-derived peptide CLIP [corticotropin-like intermediate lobe peptide; ACTH(18-39)] and its shorter fragments ACTH(25-39), ACTH(18-24), and ACTH(20-24) on sleep were investigated in rats housed under normal 12-h light/12-h dark conditions (0600 light on). CLIP (10 ng) or equimolar doses of CLIP fragments, respectively, were injected intracerebroventricularly immediately before the 8-h recording period (0800-1600). It was found that paradoxical sleep (PS) was increased by CLIP (+20%) as well as by the N-terminal CLIP fragment ACTH(18-24) (+18%) and by the pentapeptide ACTH(20-24) (+25%), whereas the C terminal fragment ACTH(25-39) was ineffective. Slow-wave sleep (SWS) was not influenced. These results clearly demonstrate that CLIP and its N-terminal fragments have selective PS-enhancing effects. CLIP and/or CLIP partial sequences are possible candidates for endogenous PS-inducing peptides involved in the physiological regulation of paradoxical sleep. PMID- 8008629 TI - POMC mRNA levels in individual melanotropes and GFAP in glial-like cells in rat pituitary. AB - In this study we demonstrated that individual melanotropes expressed differing levels of POMC mRNA. Interspersed among the melanotropes was a small population of process-bearing cells expressing GFAP. We compared cellular resolution and feasibility for quantitation of hybrids formed by oligonucleotide probes labeled with two different markers using in situ hybridization histochemistry. In hybridizations using [35S]-labeled probes the signal could not easily be assigned to individual melanotropes, although digoxigenin-labeled probes provided good cellular resolution. Heterogeneous staining intensities of individual melanotropes for POMC mRNA were measured, and relative quantitation of changes in POMC mRNA levels following interactions with the D2 dopamine receptor was performed. We combined in situ hybridization histochemistry with immunohistochemistry to demonstrate that cells within the lobe parenchyma not expressing POMC mRNA were immunoreactive for GFAP. PMID- 8008630 TI - Biotinyl C-terminal-extended motilin as a biologically active receptor probe. AB - The synthesis, purification, and characterization of biotinylated analogues of motilin are reported. The C-terminal of canine motilin was extended by the addition of a cysteine residue, and then biotinylated. Biotinyl motilin was purified by following HPLC and characterized by amino acid analysis. Biotinylation of the ligand was confirmed by ELISA assay with the avidin-biotin system. Biotinyl motilin showed similar affinity for binding to rabbit gastric membrane fraction compared to unlabeled canine motilin, and also retained functional activity in its ability to cause contraction of rabbit duodenal segments. To determine the binding of biotinyl motilin in isolated rabbit antral smooth muscle, cells were incubated with the biotinyl motilin with and without excess of unlabeled motilin. Subsequent addition of avidin-biotinylated peroxidase complex showed the distribution of reaction products over the cell surface. Bioactive biotinyl motilin provides a useful probe for the demonstration of cell surface motilin receptors and will facilitate receptor purification and characterization. PMID- 8008631 TI - Pan-neuronal expression of chromogranin A in rat nervous system. AB - Sensitive and specific in situ hybridization detection of CGA mRNA, and immunohistochemistry with an antibody recognizing the CGA(316-329) epitope within CGA and its proteolytic fragments were employed to determine whether or not CGA mRNA or protein expression are restricted to specific neuronal subpopulations within the central and peripheral nervous systems. Virtually all neurons in sympathetic, sensory, and parasympathetic ganglia examined, as well as enteric nervous system and spinal cord, expressed both CGA mRNA and the 316-329 (WE-14) CGA epitope. Chromogranin A expression was also ubiquitous within all telencephalic and diencephalic brain nuclei examined, including frontal cortex, striatum, and hippocampus. In addition, CGA mRNA was expressed in nonneuronal cells that appeared to be glia in dorsal root ganglion, spinal cord, and brain. In contrast to earlier reports, neuronal expression of CGA appears to be unrestricted within the central and peripheral nervous systems. Nonneuronal expression of CGA also occurs in the nervous system, albeit at levels much lower than in neuronal cells. PMID- 8008632 TI - Corticotropin-releasing factor stimulates cyclic AMP, arachidonic acid release, and growth of lung cancer cells. AB - The effects of corticotropin-releasing factor (CRF) on human lung cancer cell lines was investigated. Corticotropin-releasing factor increased the cAMP levels in a dose-dependent manner; CRF (100 nM) elevated the cAMP levels approximately eleven-fold using NCI-H345 cells and increased the gastrin-releasing peptide (GRP) secretion rate by approximately 70%. Similarly, sauvagine, a structural analogue of CRF, elevated the cAMP levels with a half-maximal effective dose (ED50) of 20 nM. The increase in cAMP caused by CRF and sauvagine was reversed by alpha-helical CRF(9-41). Corticotropin-releasing factor had no effect on cytosolic calcium but stimulated [3H]arachidonic acid release from NCI-H1299 cells with an ED50 of 30 nM. The increase in [3H]arachidonic acid release caused by 100 nM CRF was significantly reversed by 1 or 10 microM alpha-helical CRF(9 41). Also, CRF stimulated the clonal growth of NCI-H345 and H720 cells and the growth increase caused by CRF was reversed by alpha-helical CRF(9-41). These data suggest that CRF may be a regulatory peptide in lung cancer. PMID- 8008633 TI - Immunoreactive C-type natriuretic peptide in human adrenal glands and adrenal tumors. AB - C-type natriuretic peptide (CNP) in human adrenal glands and adrenal tumors was measured with a specific radioimmunoassay for CNP. Tissue immunoreactive (IR-) CNP concentrations were 0.54 +/- 0.40 pmol/g wet tissue (gwt) (mean +/- SD) in 14 pheochromocytomas, 0.69 +/- 0.19 pmol/gwt in six adrenocortical tumors, and 0.49 +/- 0.22 pmol/gwt in seven normal adrenal glands (cortex and medulla mixed). These concentrations were comparable to those found in tissues from human brains. Sephadex G-50 superfine column chromatography and reverse-phase high performance liquid chromatography revealed that IR-CNP in normal adrenal glands and pheochromocytoma consisted of at least two components: a component in low molecular weight form chromatographically identical to CNP-22 and the other, a high molecular weight form very similar to human CNP-53. This study has shown that IR-CNP is present in human adrenal glands and adrenal tumors with similar molecular forms and comparable concentrations to those in the human brain. PMID- 8008634 TI - Colocalization of atrial natriuretic factor and beta-endorphin in rat thymic macrophages. AB - Recent demonstration of immunoreactive (IR) atrial natriuretic factor (ANF) and beta-endorphin (beta-EP) in the thymus prompted a reexamination of the distribution and cellular localization of the two peptides within that tissue. Double labeling immunohistochemistry was carried out on gelatin-embedded cryostat thymic sections of adult male Sprague-Dawley rats. Cells stained positive with antiserum (S118), raised against rANF(1-28), were colocalized in > 95% of cases with immunofluorescent staining of IR-beta-EP(1-31). The cells were found sparsely distributed along the corticomedullary junction and in subcapsular regions. In 1- or 5-day monolayer cultures of adherent thymic cells, 15-20% of the cells stained positive for either IR-ANF or IR-beta-EP. Under these conditions, > 95% of IR-ANF or IR-beta-EP positive cells were also fluorescence stained for the rat macrophage marker ED-1. Thus, taken together with previous reports, our present findings suggest that, in the rat thymus, both ANF and beta EP are produced by the same population of macrophages. To further investigate their presence in the thymus, the contents and molecular species of the two peptides were compared over the developmental period of the animal using well characterized radioimmunoassays (RIA). Both peptides significantly increased their contents between day 2 and day 60. However, in terms of concentration, IR ANF at day 2 was approximately 50% higher than day 16 and five times greater that at day 60; in comparison the concentration of IR-beta-EP remained relatively constant and the only significant difference from day 2 being a slight increase in the day 16 animals.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8008635 TI - Gastric inhibitory polypeptide (GIP) binding sites in rat brain. AB - Synthetic porcine gastric inhibitory polypeptide (GIP) was iodinated and purified by reverse-phase HPLC and used to localize saturable [125I]GIP binding sites by radioligand binding to frozen sections of rat brain followed by autoradiography. Saturable [125I]GIP binding sites were expressed in several brain regions including cerebral cortex, anterior olfactory nucleus, lateral septal nucleus, subiculum, inferior colliculus, and inferior olive. Saturable [125I]GIP binding was time dependent, reversible, high affinity, and specific for GIP. Scatchard analysis of equilibrium binding resulted in an estimated dissociation constant (Kd) of 16-62 pM for the rat brain [125I]GIP binding sites. Peptides with amino acid sequences similar to GIP such as secretin, vasoactive intestinal polypeptide (VIP), glucagon, and peptide histidine isoleucine (PHI) only partially inhibited saturable [125I]GIP binding at concentrations approximately 10,000-100,000-fold higher than GIP. Saturable [125I]GIP binding was not observed in other rat organs surveyed such as spinal cord, pituitary, stomach, small intestine, colon, pancreas, liver, heart, or skeletal muscle. We conclude that a saturable [125I]GIP binding site with the pharmacological properties of an authentic GIP receptor is expressed in certain regions of the rat brain. PMID- 8008636 TI - Tolerance to the hypothermic but not to the analgesic effect of [D Trp11]neurotensin during the semichronic intracerebroventricular infusion of the peptide in rats. AB - The peptidase-resistant derivative of neurotensin, [D-Trp11]neurotensin, has been continuously infused intracerebroventricularly (75 ng/h) with an osmotic minipump for 10 days. On several days during this infusion the locomotor activity, the body temperature, the food intake, the body weight, and the nociceptive response in the plantar test were measured. A nonsignificant decrease of body temperature and a sustained analgesic effect were observed at each time considered. The response to a test dose of [D-Trp11]neurotensin (75 ng per rat) injected intracerebroventricularly at the 10th day of the chronic infusion revealed a complete tolerance to its hypothermic effect. Thus, it appears that the analgesic effect of [D-Trp11]neurotensin is independent of a hypothermic or an incapacitating effect of the peptide and does not give rise to tolerance after a 10-day continuous administration, in contrast to the hypothermic effect. PMID- 8008637 TI - Characteristics of receptors for VIP in rat peritoneal macrophage membranes. AB - Vasoactive intestinal peptide (VIP) receptors were investigated in rat peritoneal macrophage membranes (RPMM) using [125I]VIP as ligand. The receptor binding was rapid, reversible, saturable, specific, and dependent on time, temperature, and membrane concentration. The Scatchard analysis of binding data was consistent with the existence of two classes of VIP binding sites with Kd values of 0.60 +/- 0.08 and 275 +/- 39 nM and binding capacities of 580 +/- 71 and 72,500 +/- 810 fmol VIP/mg protein, respectively. The interaction showed a high degree of specificity, as suggested by competitive displacement experiments with several peptides structurally or not structurally related to VIP. These pharmacological studies showed the following order of potency: VIP (IC50 = 1 nM) > rGRF (IC50 = 13 nM) > PHI (IC50 = 421 nM) >> secretin. Glucagon, somatostatin, insulin octapeptide of cholecystokinin [CCK(26-33)], and pancreastatin were ineffective at concentrations up to 1 microM. Binding of [125I]VIP to membranes is markedly reduced by increasing the ionic strength of incubation medium. Treatment of membranes with dithiothreitol, trypsin, and phospholipases A2 and C resulted in a loss of the ability of these membranes to bind VIP. However, treatment with phospholipase D did not affect binding of VIP by membranes. The molecular characterization of VIP receptors in RPMM was performed after [125I]VIP cross linking to membranes using the cross-linker dithiobis (succinimidyl propionate). Sodium dodecyl sulfate-polyacrylamide gel electrophoresis of membrane proteins revealed specific [125I]VIP-protein complexes of M(r) 55,000 +/- 1700, 35,000 +/- 900, and 22,000 +/- 500. PMID- 8008638 TI - Degradation of vasoactive intestinal polypeptide by rabbit gastric smooth muscle membranes. AB - Crude membrane fractions prepared from rabbit gastric fundic muscle degraded vasoactive intestinal polypeptide (VIP) with an average specific activity of 0.96 nmol/min/mg protein at 37 degrees C, pH 7.5, and at [S]o = 0.05 mM. The relative activities towards [Leu5]enkephalin, substance P, VIP, and neurotensin were approximately 7.7, 2.0, 1.0, and 0.54, respectively. The VIP degradation was inhibited by metal chelators EDTA and o-phenanthroline. CaCl2 at 0.3-1.0 mM enhanced VIP degradation up to twofold. Phosphoramidon, captopril, and bestatin, the specific inhibitors for endopeptidase-24.11, angiotensin-converting enzyme, and aminopeptidase M, respectively, did not affect VIP degradation significantly. However, the complex mixtures of VIP fragments generated implicates action of multiple peptidases including the aforementioned three peptidases and other unidentified peptidase(s). PMID- 8008639 TI - VIP receptor/effector system in liver membranes from cholestatic rats. AB - A reduced efficacy of VIP (43% of the control) without modification in its potency (ED50 = 2.2 nM) was observed in regenerating rat liver after cholestasis (bile duct ligation). The same occurred with glucagon-stimulated adenylyl cyclase activity because the efficacy of this VIP-related peptide was also reduced (53% of the control) without changes in its potency in this experimental model. The equilibrium binding data revealed no changes in either the affinity or the VIP binding capacity of liver membranes during cholestasis. Cross-linking experiments gave the same apparent molecular mass for the liver VIP-receptor complex (52 kDa) in control and cholestatic rats. The coupling between the VIP receptor and the Gs protein was also unaffected because the sensitivity of VIP binding to GTP did not change after bile duct ligation. However, liver membranes from cholestatic rats showed a low extent of both ADP-ribosylation of the Gs-protein alpha subunit (as assessed with cholera toxin) and adenylyl cyclase stimulation by a direct effector such as forskolin. Thus, VIP-stimulated adenylyl cyclase activity is decreased in regenerating liver after cholestasis due probably to an impairment in the interaction between Gs-protein and adenylyl cyclase as well as a defect in the enzyme itself. PMID- 8008640 TI - LH-RH analogue carrying a cytotoxic radical is internalized by rat pituitary cells in vitro. AB - The binding and internalization of a cytotoxic analogue of luteinizing hormone releasing hormone (LH-RH), T-98 (agonist [D-Lys6]LH-RH linked to glutaryl-2 (hydroxymethyl)anthraquinone), by rat anterior pituitary cells was investigated. Analogue T-98 was bound to pituitary membrane binding sites for LH-RH with a high affinity (Kd = 1.2 nM) and was 17 times more potent in releasing luteinizing hormone (LH) from superfused rat pituitary cells than LH-RH. The labeling of this cytotoxic LH-RH analogue was carried out both with radioactive (125I) and nonradioactive iodine. Monoiodination of the Tyr5 residue of T-98 did not significantly affect its binding affinity but greatly decreased its LH-releasing activity to about 3% of the original value. Di-iodination in the same position lowered binding affinity twenty-threefold and further diminished LH-releasing potency. [125I]T-98 was found to bind very strongly to polystyrene, which precluded the use of regular tissue culture plasticware in our experiments. In pituitary cells cultured in glass vials, binding and internalization of [125I]T 98 were observed, which were time and temperature dependent, and which could be inhibited by excess unlabeled analogue. No enzymatic degradation of labeled T-98 was detected in the culture medium during the incubation. Our results indicate that T-98 is internalized by pituitary gonadotropes through receptor-mediated endocytosis. Because this new class of compounds was designed as anticancer drugs, our findings also suggest that this cytotoxic LH-RH agonist may also be internalized by LH-RH receptors present in breast, prostate, ovarian, and other tumors. PMID- 8008641 TI - Neuroactive peptides: unique phases in research on mammalian brain over three decades. AB - Because of the enormous growth over the last three decades of research on the role of peptides in the brain, the need became apparent to determine the status of these compounds in terms of their current research interest. Since 1965, over a quarter of a million research papers have been published on peptides that have since been classified as neuroactive. The present study was undertaken to analyze systematically the yearly trends of research emphasis in neuroactive peptides as reflected by their individual frequency of publication by year, beginning in 1966. A computer analysis of the publication characteristics was carried out using the Medline data base in which the citation search was limited to the topic brain crossed with the topic mammal. One criterion for the inclusion of a given peptide in the analysis was a frequency of 25 or more citations following its discovery, as related to the mammalian brain. The 42 peptides that met this criterion were: adrenocorticotropic hormone, angiotensin II, atrial natriuretic factor, bombesin, bradykinin, calcitonin, calcitonin gene-related peptide, carnosine, beta-casomorphin, cholecystokinin, corticotropin-releasing factor, delta sleep-inducing peptide, dynorphin, beta-endorphin, Leu-enkephalin, Met enkephalin, galanin, gastrin, glucagon, growth hormone, growth hormone-releasing factor, insulin, kyotorphin, beta-lipotropin, luteinizing hormone-releasing factor, melanocyte-stimulating hormone release inhibitory factor-1, alpha melanocyte-stimulating hormone, motilin, neurokinin A, neurokinin B, neuropeptide Y, neurotensin, oxytocin, pituitary adenylate cyclase activating polypeptide, peptide HI, prolactin, secretin, somatostatin, substance P, thyroid-releasing hormone, vasopressin, and vasoactive intestinal peptide. An overall analysis of the 298,105 papers published on these 42 peptides since 1965 revealed that the research activity of 24,742, or 8.30%, of the studies, focused on their neuroactive properties. Taken as a whole, the research on neuroactive peptides reached a peak in 1986, as reflected by the total of 1793 papers published during that year. Although the level of publication has fluctuated between 1548 and 1774 research papers over the last 6 years, it is now clear that the trend in research on neuroactive peptides has reached an asymptote today that shows no sign of deviation. A temporal analysis year by year of individual publication profiles revealed three distinct trends: 1) peptides showed a slow development in research interest and did not exceed more than 15-30 publications per year; 2) peptides exhibited a steady increase in research activity over the years that continues today; and 3) peptides displayed an initial, often intense, research emphasis that inexplicably declined, in some cases precipitously, in the mid 1980s.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8008642 TI - Structure-activity relationships for relaxation of smooth muscle by VIP. AB - Utilizing VIP and five VIP analogues, concentration-response curves for relaxation of rat mesenteric artery and rat gastric longitudinal muscle were determined for comparison with our previously published radioligand binding data on rat smooth muscle and other tissues. The biological potency of the VIP analogues in the present study compared more closely with their potency for VIP receptor binding in smooth muscle tissue (arteries) vs. other tissues (pituitary, brain, liver). PMID- 8008643 TI - [Neurologic complications of neoplasms]. AB - In course of many neoplastic diseases the variety of the neurological syndromes many appear. They may precede the primary disease or appear during its follow up. They originate from the tumor itself or may be caused by secondary metabolic disturbances in electrolytes, lesions of the kidneys or liver. Infections in the central nervous system, conditioned frequently by immunodeficiency, could also cause the onset of various, neurological symptoms. In some cases they simply may happen as the toxic side effects of applied cytostatics. PMID- 8008644 TI - [Health status of allogenic bone marrow transplantation recipients]. AB - A health status of three long-term survivors (one--5 years, two--3 years) after the allogenic bone marrow transplantation from HLA-identical siblings is discussed. All bone marrow recipients are in excellent clinical condition, any transplant-related medication is given. All patients lead a normal life. No significant developmental, hematologic or metabolic disorders are observed except one patient in whom mild abnormalities in liver enzymes activity was noted. Successful bone marrow transplantation offers the recipients a normal life. PMID- 8008645 TI - [Evaluation of complications after fine-needle biopsy of polymorphic adenoma from materials of the Otolaryngologic Clinic AM in Warsaw in the years 1983-1988]. AB - The authors, who have an ample experience with thin-needle biopsy in the routine diagnosis of head and neck tumors present the results of analysis of 56 patients with salivary glands and adenomatous tissue of the platelet adenoma. The analysis showed, that early complications after this procedure are very rare. Properly performed thin-needle biopsy assured the oncological safety to the patient. PMID- 8008646 TI - [SCC-Ag antigen in serum of patients with primary non-small cell lung carcinoma]. AB - The study aimed at evaluating SCC-Ag in patients with NSCLC, especially its predictive value following radical lung surgery. The study involved 70 patients with NSCLC and 48 patients with non-cancerous lesions to the lungs. SCC-Ag was assayed with Imx technique supplied by Abbott. Serum was tested before and 3 years after surgery. The results were analysed statistically with Wilcoxon-Fisher test. Elevated SCC-Ag levels were found in 45.7% of patients with NSCLC and in 4.1% pf patients with non-cancerous lesions. An increase in this antigen level was most frequent in patients with squamous-cell lung carcinoma (65.7%) and percentage of increased values was higher in more advanced stages of the disease (40% in I stage, 66.7% in II, and 78.9% in the III stage). During a 3-year follow up, a relationship of recurrences or metastases and SCC-Ag levels was noted. Recurrence or metastases were more frequent when antigen levels were increased both before surgery and in postoperative period. The same relationship was seen when normal values before surgery increased after surgical treatment. PMID- 8008647 TI - [Delayed results of surgical treatment of patients with cancer of the colon]. PMID- 8008648 TI - [Low levels of selenium and activity of glutathione peroxidase in blood of patients with gastrointestinal neoplasms]. AB - Selenium concentrations in the full blood and erythrocyte and plasma GSH-Px activity were determined in patients with cancer of the stomach, colon and rectum. The results were compared with those in the group of healthy subjects. Blood samples were collected into heparinized tubes prior to surgery. Selenium concentrations in the full blood and plasma were lower (75.5 ng/mL and 56.2 ng/ml, respectively) in patients with the cancer of the stomach than healthy subjects (99.5 ng/ml and 78.5 ng/mL, respectively; p < 0.0001). Concentration of this element in both full blood and plasma was also lower in patients with cancer of the colon and rectum (77.7 ng/mL and 61.0 ng/ml, respectively; p < 0.0001). Erythrocyte and plasma GSH-Px activity was also significantly lower (p < 0.001) in patients with cancer of the stomach than in healthy subjects, and amounted to 13.6 U/g Hb and 188 U/L, respectively. Activity of this enzyme in patients with cancer involving lower segment of GI tract amounted to 15.9 U/g Hb and 190 U/L of plasma, and was significantly lower (p < 0.001) than in normal subjects in whom it amounted to 21.0 U/g Hb and 256 U/L of plasma. PMID- 8008649 TI - [Failure of therapy in non-seminomatous tumor of the testes]. AB - Sixty four patients with non-seminomatous tumors of the testes were treated with chemotherapy with cisplatin during 12 consecutive years. A group of 22 (34.3%) patients in whom therapy failed was analysed. Nineteen of them (29.6%) died, and 3 (4.6%) live with the symptoms of disease. At the beginning of therapy 13 (59%) patients presented with III degree of clinical advancement of cancer. Complete remission after induction treatment was achieved in 6 (27.7%) patients but all experienced recurrence (4 early and 2 late). Prolonged survival since hemicastration in the group of patients with complete remission amounts to approximately 36.5 months whereas in the group of partial remission only 13.6 months. These results are similar to those reported by leading medical centres. PMID- 8008650 TI - [Antiemetic effect of ondansetron in patients treated with combined antineoplastic regimens which include cisplatin]. PMID- 8008651 TI - [Vasculitis in the course of Lesniowski-Crohn disease and ulcerative colitis]. AB - Two cases of the acute vasculitis which constituted a considerable diagnostic problem are presented. Interdisciplinary diagnosis has led to the detection of rare intestinal disorder of immunologic origin. PMID- 8008652 TI - [Neurologic complications of disseminated intravascular coagulation in a patient with a stomach neoplasm]. AB - A case of the female patient with gastric carcinoma with metastases into lymph nodes and vertebrae is presented. Generalized DIC with subarachnoid haemorrhage confirmed by CSF examination has occurred in the course of the disease. Applied treatment failed. PMID- 8008653 TI - [Leiomyoma of the stomach as a cause of hemorrhage from the upper segment of the gastrointestinal tract]. AB - Two cases of female patients operated fo the tumors of the stomach are presented. Result of histologic examination was rather surprising in both cases--leiomyoma. PMID- 8008654 TI - [Infection with Helicobacter pylori as a risk factor for stomach cancer]. PMID- 8008655 TI - [Gonadal disorder as a result of adverse reaction to antineoplastic drugs- diagnosis, symptoms, prevention and treatment]. AB - The past three decades have shown the increasing success of chemotherapy as the treatment of malignancies. This therapeutic success has focused attention on the associated gonadal toxicity. Cytotoxic agents may induce infertility and endocrine disfunction. Data for analysis were provided by studies on gonadal function after chemotherapy for: Hodgkin's disease, acute lymphocytic leukemia, non-Hodgkin's lymphoma, breast cancer; renal disease, bone-marrow transplantation. The likelihood of developing chemotherapy-induced damage depended on the chemotherapeutic regimen and prescribed dose, illness, sex and degree of gonadal activity at the time of treatment. Despite of the high frequency of chemotherapy-induced gonadal damage its prevention has received a little attention. LH-RHA and oral contraceptive therapy and testosterone have been tested to a limited extent of gonadal toxicity. Usually in male endocrine disfunction of testis does not need to be treated because it is moderate and does not cause any clinical symptoms. In female hormonal substitution seems to be necessary to decrease unpleasant feelings connected with menopause induced by chemotherapy. Further investigations should considered use of new cytotoxic agents without gonadal toxicity or use of new drugs which can better protect gonadal function. PMID- 8008656 TI - [Diet and colonic neoplasms]. PMID- 8008657 TI - [Use of biochemical tumor markers in the urologic clinic]. PMID- 8008658 TI - [Abnormal TSH release syndrome of neoplastic etiology]. PMID- 8008659 TI - [Sultamicillin and cefuroxime axetil in the ambulatory treatment of exacerbated chronic bronchitis]. PMID- 8008660 TI - [Sultamicillin for prophylaxis of septic complications of gastric and enteric surgery]. PMID- 8008661 TI - [Sultamicillin in treatment of genito-urinary infections]. PMID- 8008662 TI - [Sultamicillin in treatment of suppurative skin disorders]. PMID- 8008663 TI - [Sultamicillin in treatment of odontogenic states, jaw and mouth infections]. PMID- 8008664 TI - [Clinical pharmacology of sultamicillin]. PMID- 8008665 TI - [Sultamicillin in treatment of infections in children]. PMID- 8008667 TI - [Chemotaxis and spontaneous migration of neutrophil leukocytes from patients with diabetes]. AB - The spontaneous migration and chemotaxis of leukocytes has been measured in 103 diabetic patients with 1 ans 2 type diabetes controlled and uncontrolled diabetes as well as in patients those treated with oral hypoglycemic drugs or insulin. The obtained results have been compared with appropriate parameters from 32 healthy individuals. Our findings indicate increase of spontaneous migration of PMN. The disturbances in PMN functions are not related to diabetes type. Treatment with oral diabetic drugs resulted an decrease in spontaneous migration values. PMID- 8008666 TI - [Sultamicillin in treatment of acute middle ear infection in children]. PMID- 8008668 TI - [Renal hemodynamics in patients with short-lasting diabetes mellitus type I]. AB - Parameters of renal hemodynamics have been determined in 30 male patients with diabetes mellitus, lasting for 1-24 months (mean 0.9 +/- 0.7 year), and in 19 healthy men of the same age. Patients' age ranged from 17 to 33 years (mean 27.5 +/- 5.0). All examined subjects have been normotensive (according to WHO criteria). Glomerula filtration rate with the aid of 51CrEDTA, and ERPF with 125I hippurate have been determined. Mean GFR values have been significantly higher in diabetics than that in healthy men (142.9 +/- 29 vs 118 +/- 20 ml/min per 1.73 m2). Hyperfiltration (GFR over 140 ml per minute) has been found in 15 patients (50%). ERPF has also been higher in diabetic patients (929.2 +/- 230 vs 821.5 +/- 192 ml/min). This difference has been insignificant. No correlation between arterial blood pressure and GFR, ERPF, filtration fraction (FF), and RVR has been found. PMID- 8008669 TI - [Effect of diabetes mellitus therapy on activity of erythrocyte superoxide dismutase]. AB - An activity of erythrocyte SOD, HBA1C levels and FA activity have been determined in 17 patients with diabetes mellitus type I and 15 healthy subjects. It was found that the treatment of diabetes mellitus has no effect on the SOD activity. PMID- 8008670 TI - [Evaluation of clinical usefulness of direct drug injections for increasing local circulation, into cavernous bodies of the penis for treatment of erection impotence in patients with diabetes mellitus]. AB - The study aimed at comparing an effectiveness of drugs increasing local blood flow injected into cavernous bodies of penis in the treatment of erective impotence in diabetic patients. Fifteen diabetic patients aged between 33 and 60 years with impotence lasting for 4 years have been selected. Patients have been treated with papaverine HCl in the dose of 20-40 mg, papaverine HCl in the same dose combined with phentolamine 5 mg, and prostaglandin E1 in the dose of 20 micrograms. Each patient has been all tested drugs. The most favourable results, i.e. most effective and without adverse reactions (priapism), have been produced by prostaglandin E1 which seems a drug of choice in the treatment of erective impotence in patients with long-lasting diabetes mellitus. PMID- 8008671 TI - [Recurrent skull neuropathy during the course of diabetes mellitus--case report]. AB - This study presents a case of a 73 year old woman who has suffered from diabetes mellitus for 8 years and has had 6 isolated cranial nerves palsies within a period of 7 years. The last are-because of which she was treated in Department of Neurology in July 1992--concerned left oculomotor nerve. The coincidence of metabolic and vascular disorders provoke authors to take a wide diagnostics and discussion on diabetic ophthalmoplegia problem. PMID- 8008672 TI - [Calcitonin in treatment of diabetic foot syndrome]. AB - A case of a 36-year patient with persistent diabetes mellitus of type I and gangrene of the foot is presented. Calcitonin has been used to treat osteitis and inflammation of the adjacent soft tissues. Despite performed surgery and conservative treatment, destruction of the bones has been progressing, and could lead to the high amputation of the extremity. Calcitonin produced an increase in bone, massive calcification around bone stumps, and anastomosis within one year. An acceleration of the wound healing has also been noted. Taking calcitonin mechanism of action and the clinical course of this case into consideration, it seems justified to use calcitonin in the treatment of gangrene of the foot in diabetes. PMID- 8008673 TI - [Metabolic care of patients with diabetes treated surgically]. PMID- 8008674 TI - [Preclinical period in diabetes mellitus type I]. PMID- 8008675 TI - [Allergy to insulin]. AB - Allergic reactions to insulin have been noted within a few years following the completion of therapy. Allergy to insulin may be manifested by discrete local skin reactions (the majority of diabetics) or generalized reaction (rarely). Allergy to insulin may be produced by: immunogenicity of the commercial animal insulin preparations, low purity of insulins, different pattern of therapy with insulin, and genetic factors. The treatment of allergy to insulin consists of a proper injection technique and optimum choice of insulin preparation. In case of generalized allergic reactions desensitization is a therapy of choice. Antihistamine agents and corticosteroids may be helpful in some cases. PMID- 8008676 TI - [Nephropathy in the course of non-insulin-dependent diabetes mellitus]. PMID- 8008677 TI - [Glucose tolerance and insulin secretion in patients with hyperthyroidism. Pathogenesis of disturbances and therapeutic consequences]. AB - Abnormalities of carbohydrate metabolism have been frequently reported in hyperthyroid patients. Disturbed glucose tolerance might be due to increased hepatic glucose production, altered insulin metabolism, increased response to beta-adrenergic stimuli and elevated plasma FFA levels. These disturbances very often disappear when remission of thyrotoxicosis is attained during-treatment with thyrostatic drugs. Non-selective or selective beta 1-adrenoceptor blocking agents does not impair the glucose stimulated insulin secretion or the carbohydrate tolerance and impaired glucose tolerance disappear when glycolytic blockade is attained. PMID- 8008678 TI - [Commercial diabetic diets]. PMID- 8008679 TI - [Obesity in patients with diabetes in two Warsaw out-patient clinics: Diabetic Consulting Unit ZOZ Warsaw Praga Pld. and Diabetic Consulting unit ZOZ Warsaw Praga Pln]. PMID- 8008680 TI - [Levels of free fatty acids in plasma, tissue utilization coefficient of glucose K and insulin secretion following intravenous glucose load in hyperthyroid patients treated with propranolol or acebutolol]. AB - The study aimed at determining relationship between plasma free fatty acid (FFA) and impaired glucose tolerance in hyperthyroid patients prior to and after the treatment with propranolol or acebutolol, i.e. following lipolytic blockade leading to a decrease in plasma FFA levels. The study included 31 untreated hyperthyroid patients and 12 normal subjects serving as a matched control group. IVGTT was performed in all subjects. Venous blood specimens were collected at 0, 3, 5, 15, 30, 60, and 120 minutes following intravenous glucose load (0.33 g/kg body weight during 3 minutes). Nineteen patients with normal K values were randomized to groups treated either with propranolol in the daily dose of 120 mg (10 patients) or 400 mg acebutolol (9 patients). Twelve patients with low K values were randomized to groups treated with either propranolol (5 patients) or acebutolol (7 patients). The second IVGTT was performed after 7 days of therapy. Glucose, FFA and insulin levels were determined in all blood samples whereas T3 and T4 were determined in samples taken at 0 minute. Plasma T3, T4 and insulin levels were assayed with radioimmunological technique, glucose--with glucose oxidase, and FFA--colorimetrically. Significantly higher plasma FFA levels were found in patients with low K values in comparison with control group. There were no differences in plasma FFA levels in both hyperthyroid patients and normal subjects. Acebutolol but not propranolol normalized K value whereas propranolol (but not acebutolol) significantly decreased acute phase of insulin secretion. Plasma glucose and insulin levels as well as K value were not altered during propranolol acebutolol therapy in patients with normal K value.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8008681 TI - Role of the autopsy in congenital cystic hygroma. AB - Sixteen cases of congenital cystic hygroma were identified through a retrospective review of surgical pathology and autopsy records. Tissue sections of the cystic hygromas were available in 10 cases and were examined histopathologically and for reactivity to factor VIII antiserum. Of 13 cases with ultrasound examinations, cystic hygroma was diagnosed prenatally in 9. In 11 cases with successful karyotyping, six were 45, X. Histopathologic observations of lymphatic vascular architecture were apparent in 10 cases, and immunoreactivity of the endothelium to factor VIII antiserum was preserved regardless of the degree of autolysis. PMID- 8008683 TI - Lingual bronchogenic cyst in a child: an unusual site of presentation. AB - We describe a 4-year-old hispanic male with a bronchogenic cyst (BC) in the base of the tongue. To our knowledge, a BC has not been previously reported in the oral cavity. BC is a developmental anomaly believed to originate from abnormal detachments of accessory lung buds from the ventral foregut. We postulate that the unusual location of the BC in the present case is related to the primitive foregut origin of tongue epithelium posterior to the foramen cecum and the sulcus terminalis. A BC in the base of the tongue appears to represent the most proximal expression of aberrant accessory lung bud detachment from the primitive foregut. PMID- 8008682 TI - Intestinal spirochetosis in children: report of two cases. AB - Two cases of intestinal spirochetosis in two children are reported. The first patient, a 7 1/2-year-old boy, presented with diarrhea and rectal bleeding. After the diagnosis was made by a rectal biopsy, he was given metronidazole and neomycin. Symptoms persisted despite a further rectal biopsy that showed clearance of the organisms. Appendiceal spirochetosis was an incidental finding in our second patient, an 8-year-old girl who presented with acute abdominal pain and in whom mesenteric adenitis was diagnosed clinically at laparotomy. The possible pathogenic mechanisms causing clinical symptoms are discussed. PMID- 8008684 TI - Cutaneous bronchogenic cyst of the back: a case report and review of the literature. AB - Cutaneous and subcutaneous cysts with ciliated pseudostratified columnar (respiratory) epithelium present a diagnostic dilemma. We report a case of a bronchogenic cyst occurring on the back. The differential diagnosis includes branchial cleft cyst, thyroglossal duct cyst, cutaneous ciliated cyst, and mature cystic teratoma. We review reports of extrapulmonary bronchogenic cysts and discuss their possible embryology. PMID- 8008685 TI - Hypertrophic gastropathy in a newborn: a case report and review of the literature. AB - A newborn with hypoalbuminemia, hematochezia, and hypertrophic gastropathy is described. These features are similar to those reported in association with prostaglandin therapy in newborns, as well as those described in so-called Menetrier's disease. Very few cases of hypertrophic gastropathy have been reported in children and fewer still verified histologically; only three other cases have been reported in newborns. The clinical and pathologic features of hypertrophic gastropathy in children, as well as its close association with eosinophilic gastroenteritis and with prostaglandin therapy, are discussed. PMID- 8008687 TI - Histopathological findings in a male with late-onset ornithine transcarbamylase deficiency. AB - Late onset of symptoms in a 12 1/2-year-old male with ornithine transcarbamylase (OTC) deficiency were associated with unusual histological features in the liver. The patient presented with an acute onset of hyperammonemia and altered mental status after a 2-day prodrome of vomiting and lethargy. Physical examination showed a combative and disoriented male with icteric sclerae but with no fever or hepatomegaly. The plasma ammonia level was 282 microM. Enzyme assays of liver tissue obtained by percutaneous needle biopsy showed OTC activity of approximately 3% of normal; carbamyl phosphate synthetase was normal. Histopathological findings included severe microvesicular centrilobular steatosis. Hepatic architecture and reticulin framework were well preserved. Many hepatocyte nuclei were filled with glycogen. Electron microscopy showed mitochondria that were rounded and expanded with cristae at the edge of the mitochondrial membrane. In contrast to other reports, only slight variations in size and shape were seen. Megamitochondria and intramatrical paracrystalline inclusions were not identified. The cytoplasm contained scattered fat globules, peroxisomes, and dilated smooth endoplasmic reticulum. The prominent mitochondrial abnormalities commonly found in OTC deficiency were notably absent. PMID- 8008686 TI - Composition of the inflammatory infiltrate in pediatric penile lichen sclerosus et atrophicus (balanitis xerotica obliterans): a prospective, comparative immunophenotyping study. AB - Dermatopathological evaluation of pediatric preputial inflammatory disease rarely allows for specific diagnosis other than pediatric penile lichen sclerosus et atrophicus (balanitis xerotica obliterans, LSA/BXO). A prospective immunopathological study was performed on 20 consecutive, unselected, clinically and histopathologically confirmed LSA/BXO cases to determine the relative presence of T and B lymphocytes. There were seven cases with early stages of disease, eight with florid disease, and five with later stages of disease. Two ritual circumcision specimens and 12 specimens with non-LSA/BXO balanitis, collected during the same period, were used as controls. The infiltrate in LSA/BXO patients was wholly composed of T cells (positive with UCLH-1 antibody) in all cases. B cells (positive with L-26 antibody) were found only focally in small, discreet, easily recognizable (follicular or early follicle-like) aggregates, positioned slightly deeper than the band-like infiltrate of T cells. T cells were inconspicuous in 9 of the 12 control specimens. In the three other controls, T cells were much more obvious and these patients showed clinical features possibly suggestive of LSA/BXO in early, prediagnosable phases of development. We conclude that limited immunophenotyping may be a useful adjunct to diagnosis in pediatric cases in which only limited tissue is available or the disease may be more difficult to classify with confidence. PMID- 8008688 TI - Renal tubular dysgenesis present in a newborn with meconium ileus. AB - The combination of renal tubular dysgenesis (RTD) and meconium ileus in a native Israeli is presented for the first time. The clinical diagnosis was oligohydramnios and abruptio placentae, respiratory failure, and anuria refractory to treatment. The autopsy revealed meconium ileus and meconium peritonitis. RTD was established by the detection of a monomorphous undifferentiated population of tubules, absence of proximal tubules, and dense epithelial membrane antigen immunoreactivity of all tubules. The lack of alpha 1 antitrypsin- and lysozyme-immunoreactive tubules was first revealed in the kidney with RTD. These findings extend the possibilities of RTD detection. PMID- 8008689 TI - Cell kinetic analysis in pediatric brain and spinal tumors: a study of 117 cases with Ki-67 quantitation and flow cytometry. AB - We present cell kinetic data including Ki-67 quantitation and flow cytometry on 117 pediatric brain/spinal cord tumors and review the literature. Although, in general, these proliferation indices are in agreement with the histologic grade, they are useful in prognostication in some instances when the histological features of malignancy are equivocal. Specific examples in which flow cytometry may prove particularly useful in this context are childhood ependymomas, which do not show frank anaplasia but have cellular foci with focal increase in mitoses, and choroid plexus neoplasms, where elevated S phase fractions have been associated with an adverse outcome. Thus Ki-67 quantitation and flow cytometry not only serve as useful adjuncts to conventional histologic grading but also in specific instances may provide new information on tumor prognosis. PMID- 8008690 TI - Lethal congenital muscular dystrophy with arthrogryposis multiplex congenita: three new cases and review of the literature. AB - Congenital muscular dystrophy (CMD) comprises a heterogeneous group of muscle disorders. We report on two stillborn sibs with early lethal CMD and a prematurely born boy who died within minutes after birth. The pregnancies were complicated by polyhydramnios. All presented with arthrogryposis multiplex congenita, severe muscle wasting, lung hypoplasia, and hydrops. The muscle biopsies showed fibrosis, variation in fiber size, and extensive fat replacement compatible with muscular dystrophy. Fatal CMD seems to be distinct from CMD with survival after birth and is probably autosomal recessively inherited. PMID- 8008691 TI - Anomalous coronary arteries: a multicenter pediatric autopsy study. AB - Anomalous coronary arteries (ACAs) are a potential cause of myocardial ischemia resulting in arrhythmias, angina, infarction, and sudden death. We analyzed 7857 pediatric autopsy cases from four tertiary centers to gain an overall picture of the range and significance of ACAs within this pediatric autopsy population. The incidence of ACAs was 0.5%, with ectopic origin from the aorta (43%) being most frequent, followed by ACA arising from the pulmonary trunk (40%). The mean age at death was 2.2 years (4 h-14 years). ACAs were associated with other anomalies in 57% of cases, 43% of these being cardiac defects. Growth retardation was noted in 50% of the cases. Examination of the heart showed cardiomegaly in 92% of cases, which was marked (> 95 percentile) in 63%, but histologically apparent ischemic damage was seen in only 50% of cases. ACAs arising from the pulmonary trunk were associated with earlier death (1.4 years), more frequent cardiomegaly (100%), and more frequent myocardial scarring (92%) than other types of anomalies. Although the terminal presentation was sudden death in 45% of cases, ACAs associated with other cardiac defects presented mainly with problems related to the latter anomalies. The results highlight the need to examine coronary arteries carefully during the pediatric autopsy. Not only are the positions of the coronary artery ostia important, but also the variations in the angles of arterial take-off, initial courses through the aortic adventitia, subsequent courses, and presence of ostial ridges or membranes that may result in significant compromise of blood flow. PMID- 8008692 TI - Congenital laryngeal lesions: pathology study using serial macrosections and review of the literature. AB - This description of congenital laryngeal lesions is presented with a focus on the information derived from the specimens collected for the Laryngeal Development Laboratory at the Children's Memorial Hospital in Chicago from 1975 to 1992. During this period, 115 laryngeal specimens were obtained, 33 of which were found to have congenital laryngeal anomalies. Two specimens are thought to have laryngomalacia; 4, thyroid cartilage anomalies; 1, absence of the epiglottis; and 29, cricoid cartilage deformities. Of the cricoid cartilage deformities, 1 had large anterior lamina; 1, generalized thickening; 8, elliptical shape; 4, flattened shape; 8, occult cleft larynx; 1, partial cricoid cleft; 3, complete cricoid cleft; and 8, fragmented or distorted shape. Some specimens have more than one type of anomaly. PMID- 8008693 TI - Focal and segmental glomerulosclerosis in children with reflux nephropathy. AB - A histological review of 86 pediatric nephrectomy specimens from patients with vesicoureteric reflux (with or without apparent obstruction at the vesicoureteric junction) investigated the relationship between the presence and extent of focal and segmental glomerulosclerosis (FSGS) and coexisting renal hypoplasia and postnatally acquired cortical damage. FSGS was found in 18 patients, 9 of whom were less than 5 years old. There was no significant association between the presence (or grade) or absence of FSGS and age at nephrectomy, gender, presence or absence of obstruction, and severity of hypoplasia and/or postnatally acquired cortical loss. FSGS was absent from 18 hypoplastic kidneys without vesicoureteric reflux (although of relatively young age), 40 normally developed kidneys age matched with the index population, and 72 nephrectomy specimens without vesicoureteric reflux (except in 2 known cases of focal segmental glomerulonephritis). Within the index population FSGS was significantly (P < .01) associated with hypertension, and hypertension was significantly associated with proteinuria (P < .001) but not with an abnormal contralateral kidney. There was no significant association between FSGS, proteinuria, and an abnormal contralateral kidney. Our results were unexpected when interpreted within a pathogenesis for FSGS of glomerular "hyperfiltration." They may, at least in the pediatric age group, indicate a possible role for other mechanisms in the development of FSGS. PMID- 8008694 TI - Molecular biology primer for the pediatric pathologist. AB - Recent advances in the knowledge of molecular events of cell growth and differentiation have provided considerable gains to the understanding of neoplasia. Along with this understanding, molecular biology has yielded many new techniques of great potential for diagnostic use. This review illustrates, in general terms, current models of gene regulation, intracellular signal transduction, and the regulation of cell division that are relevant to pediatric pathologists. These concepts are used to examine the molecular pathology of three pediatric tumors: retinoblastoma, Wilms' tumor, and neuroblastoma. In addition, molecular biology techniques potentially useful to pediatric pathologists are discussed, with examples of some possible applications of these techniques. Hopefully, this review portrays the relevance of molecular biology to pediatric pathologists and serves as a useful guide to the interpretation of the molecular pathology literature. PMID- 8008695 TI - Thyroid/cervical teratomas in children: immunohistochemical studies for specific thyroid epithelial cell markers. AB - Pathological and immunohistochemical findings for specific thyroid epithelial cell markers in thyroid/cervical teratomas from four children are reported. All tumors showed components from the three germinal cell layers. Neoplastic thyroglobulin-immunoreactive thyroid follicles occurred in three intrathyroid teratomas, but the findings were negative in a cervical teratoma in which evidence of its thyroid origin could not be ascertained. As previously suggested on histological grounds, thyroid tissue, other than normal trapped thyroid follicles, is not an infrequent component of cervical teratomas. We found no evidence to support an ultimobranchial origin for these tumors, as previously suggested by Roediger et al. (19), because no calcitonin immunoreaction was observed. PMID- 8008697 TI - Controlled drug release of highly water-soluble pentoxifylline from time-limit disintegration-type wax matrix tablets. AB - A pulsatile drug release system with a dry-coated tablet containing pentoxifylline was investigated for controlling drug release in the gastrointestinal tract. The system consisted of a core tablet with disintegrator and outer layer, which obtained compression from the ground mixtures of pentoxifylline and behenic acid. Drug release from a dry-coated tablet was investigated at 37 degrees C in JPXII 2nd fluid at pH 6.8. The drug release from the outer layer was fitted to the Cobby model. The drug release from the wax matrix increased significantly after tablet distintegration; therefore, the drug release profiles showed typical sigmoidal curves. The disintegration time depended on the weight fraction of the core tablet, and the drug release rate after disintegration increased with increasing drug concentration in the core tablet. The relationship between the time required for 50% drug release and the disintegration time was linear, indicating that the drug release rate was controlled by regulating the disintegration time. PMID- 8008696 TI - Congenital adrenal hypoplasia due to isolated familial ACTH deficiency. PMID- 8008698 TI - Physicomechanical characterization of the extrusion-spheronization process. I. Instrumentation of the extruder. AB - Extrusion-spheronization is a popular means of producing spheres which can be coated to form a controlled-release system. In the extrusion process, stress is necessary to force a wet mass through small orifices, and as a result, frictional heat builds up at the screen. Therefore, the quantitative measurement of the screen pressure and screen temperature is described and shown to provide objective measures of extrudability. A strain gauge load cell was mounted tangentially to the screen of a Luwa EXDS-60 extruder with a specifically fabricated holder. The load cell output was calibrated in terms of pressure inside the screen with a special rubber plug system. A fast-response thermocouple was used to measure the screen temperature. Experiments with 50/50 lactose/Avicel PH101 revealed that a linear relationship exists between the amount of water used in the granulation and the screen pressure, that the percentage open area of the screen determines the rank order of the screen pressure, and that the maximal yield of 18/25-mesh cut pellets was uniquely related to the screen pressure. Also, a high degree of correlation was observed between the screen pressure and the screen temperature. PMID- 8008699 TI - Transport of low and high molecular peptides across rabbit Peyer's patches. AB - The permeability of peptides across rabbit jejunal epithelium (JE) and Peyer's patches (PP) was compared. Kyotorphin (L-tyrosyl-L-arginine) was almost completely hydrolyzed during its membrane transport in both PP and JE, but [D Arg2]Kyotorphin (L-tyrosyl-D-arginine) was less hydrolyzed in PP than in JE. Since the permeability of intact [D-Arg2]Kyotorphin was almost equal in PP and JE, no superiority of PP to JE was found for dipeptide transport. More intact fluorescein isothiocyanate (FITC)-labeled bovine serum albumin (FITC-BSA) and concanavalin A (FITC-Con A) were transported in PP than in JE. At both absorption sites, the transport of the intact FITC-Con A was superior to that of the intact FITC-BSA. Colchicine significantly reduced the total transport of the intact and degradation forms of both peptides and the reduction ratio was greater in PP than in JE. Accordingly, it was suggested that PP can be used as prominent absorption sites for polypeptides since they have lower peptidase activity and higher endocytosis activity than JE. PMID- 8008700 TI - An enzyme-linked immunosorbent assay (ELISA) for quantitation of adducts of granulocyte-macrophage colony stimulating factor (GM-CSF) and human serum albumin (HSA) in stressed solution mixtures. AB - HPLC analyses of GM-CSF in solution mixtures containing both GM-CSF and HSA showed losses of GM-CSF which could not be accounted for using conventional electrophoretic and/or RP-HPLC techniques. Further investigation of these mixtures by immunoblotting and by immunoaffinity chromatography demonstrated the presence of high molecular weight (> 67,000 GM-CSF related species. No such species was detectable in solutions of GM-CSF alone. This experiment pointed to the formation of an adduct between GM-CSF and HSA in the solution mixtures. To probe further the hypothesis of a GM-CSF/HSA adduct, an immunologically based test was conceived which could react only with this type of hybrid molecule. A sandwich enzyme-linked immunosorbent assay (ELISA) was developed using two antibodies, anti-GM-CSF (capture antibody) and anti-HSA (detection antibody), as part of the quantitation of GM-CSF/HSA adducts. After confirming its existence by ELISA, a GM-CSF/HSA adduct was isolated from the solution mixture containing both GM-CSF and HSA. This isolate served as a primary reference standard in the ELISA assay. The immunoassay has a subnanogram sensitivity and is highly specific for GM-CSF/HSA adducts in the presence of either free GM-CSF or free HSA. As a verification, conjugates of GM-CSF/HSA were synthesized using a cross-linking reagent. These covalent conjugates reacted positively in the ELISA and are employed as a convenient alternative reference standard. PMID- 8008701 TI - Plasma factor triggering alternative complement pathway activation by liposomes. AB - Several plasma components, such as complement (C) components, play a role in the clearance of liposomes from the circulation. The interactions between liposomes and the C system were investigated in this study. Multilamellar vesicle (MLV) liposomes, which were damaged by activation of the complement, became susceptible depending on the density of cetylmannoside (Man) on the liposome membrane, and activation proceeded through the alternative C pathway as observed for liposomes without Man (PC-MLV) (K. Funato et al., Biochim. Biophys. Acta 1103:198-204, 1992). In addition, the capacity of Man-modified liposomes (Man-MLV) to activate the alternative C pathway was abolished by preadsorption of plasma with Man-MLV but not with PC-MLV. The results suggest that a specific plasma factor adsorbed with Man-MLV was responsible for the augmentation of the C activation and, further, that the rapid clearance of Man-MLV from the circulation is caused by both enhanced C-mediated liposome permeability and enhanced C-mediated phagocytosis of liposomes. PMID- 8008702 TI - Comparative analysis of percutaneous absorption enhancement by d-limonene and oleic acid based on a skin diffusion model. AB - Percutaneous absorption-enhancing effects of d-limonene and oleic acid were investigated using three model drugs with different lipophilicities in in vitro diffusion experiments with guinea pig skin. Pretreatment of the skin with d limonene resulted in a large penetration enhancement for the lipophilic butylparaben (BP) and amphiphilic 6-mercaptopurine (6-MP) but had little effect on the hydrophilic mannitol (MT). Oleic acid caused a large effect only on 6-MP penetration. The penetration profiles were analyzed with a two-layer skin diffusion model consisting of stratum corneum with polar and nonpolar routes and viable epidermis plus dermis. Through curve-fitting, six parameters corresponding to drug diffusivity and partitioning in these three regions of the skin were obtained, and the mechanisms of enhancers were assessed in comparison with those of 1-geranylazacycloheptan-2-one (GACH) reported previously. Increased penetration was caused mainly by modification of the barrier property of the nonpolar route in the stratum corneum in all cases. In the nonpolar route, d limonene increased mainly drug diffusivity, while GACH enhanced predominantly drug partitioning. On the other hand, oleic acid moderately increased both parameters. PMID- 8008703 TI - Controlled release of paracetamol from amylodextrin tablets: in vitro and in vivo results. AB - Amylodextrin is a suitable excipient for the design of solid controlled-release systems. The release of paracetamol from tablets containing 30% drug and 70% amylodextrin was studied in vitro and in vivo. In vitro dissolution profiles showed almost-constant drug release rates during 8 hr, when measured in 0.05 M buffer, pH 6.8. Peroral administration of the tablets to man showed almost constant paracetamol plasma levels up to 14 hr, as compared to fast absorption and fast elimination of a reference paracetamol solution. The plasma profiles of eight volunteers demonstrated a small intersubject variability during the first day after tablet administration. Increasing variability and decreasing plasma levels during the second day were caused by excretion of tablets from the bodies. Cumulative input as a function of time showed near-zero-order drug release during the first day. The in vivo results indicate that amylodextrin tablets are not hydrolyzed by alpha-amylase, present in the gastrointestinal tract. PMID- 8008704 TI - Pharmacokinetic analysis of the absorption enhancing action of decanoic acid and its derivatives in rats. AB - The enhancing action of decanoic acid (C10) and its derivatives on mucosal absorption of phenolsulfonphthalein (PSP) in the jejunum or colon was analyzed using pharmacokinetics in rats. After administration of a solution containing PSP and an enhancer [C10, 2-hydroxydecanoic acid (2-OHC10), or 3-hydroxydecanoic acid (3-OHC10)] into the jejunal or colonic loop, the amounts of PSP and enhancer remaining in the loop and/or plasma PSP concentration were determined periodically. 2-OHC10 exhibited a greater absorption enhancing potency than C10, while 3-OHC10 was less effective. Disappearance of residual PSP from the loop ceased after complete absorption of the enhancer. The enhancer-induced disappearance rate constant of PSP correlated well with the product of the enhancer disappearance rate and its capacity to sequester calcium ions. In conclusion, the enhancement of PSP mucosal absorption by C10 and its derivatives is consistent with a pharmacokinetic model, assuming that the enhanced membrane permeability of PSP depends on the enhancer disappearance kinetics from the loop and its calcium ion sequestration capacity. PMID- 8008706 TI - Solubility enhancement of nucleosides and structurally related compounds by complex formation. AB - Water-soluble vitamins, amino acids, and nontoxic pharmaceutical excipients were studied as solubilizing agents for poorly water-soluble adenine (nucleic acid base), guanosine (nucleoside), and structurally related drugs (acyclovir and triamterene). The apparent solubility of the substrates (adenine, guanosine, acyclovir, or triamterene) was appreciably increased by forming complexes with the ligands (vitamins, amino acids, or other ligand). Apparent association constants (Ka) values were measured at 25 degrees C in pH 7 phosphate buffer using phase solubility analysis. The effect of combination ligands on substrate solubility was also studied. Additive solubility enhancement was obtained for several ligand pairs. PMID- 8008705 TI - Diffusion and metabolism of prednisolone farnesylate in viable skin of the hairless mouse. AB - The diffusion and metabolism of prednisolone 21-farnesylate were investigated in viable skin of the hairless mouse in vitro. The prodrug ester was extensively metabolized in viable skin, while it was stable in the donor and receptor solutions. The rate of appearance of the prodrug and its metabolite prednisolone was markedly influenced by the direction of the skin placed between the in vitro diffusion half-cells. The rate of bioconversion of the prodrug was determined as a function of the distance from the surface of the skin. The prodrug was increasingly metabolized with the distance from the surface of the skin, indicating that the responsible enzymes are enriched in the lower layers of the viable skin. A model with linearly increasing enzyme activity in the viable skin accounts for the in vitro profiles of the diffusion/metabolism of the prodrug in the viable skin of hairless mouse. PMID- 8008707 TI - Enhanced hepatic uptake of liposomes through complement activation depending on the size of liposomes. AB - The objective of this study was to differentiate the roles of opsonins and phagocytic cells in the size-dependent hepatic uptake of liposomes in the submicron region. The extent of opsonization decreased with the decrease in size of liposomes (from 800 to 200 nm in diameter) and no enhancement of uptake was observed at 200 nm. There was no effect of liposome size on the uptake of unopsonized liposomes. Serum was pretreated with empty liposomes of each size and its opsonic activity was measured in the perfused liver. The small liposomes could not consume the opsonic activity, while the larger ones did so substantially. These results suggest that opsonins bind to liposomes depending on the size of liposomes and phagocytic cells take up liposomes in proportion to the extent of opsonization. Size-dependent liposome degradation in serum was also found, which was consistent with the size-dependent complement activation, because liposomes with this composition have been shown to be degraded by complement. The mechanism of opsonization was examined by treating serum at 56 degrees C for 30 min or with anti-C3 antiserum. Since both treatments inhibited the opsonic activity, the hepatic uptake of liposomes is considered to occur via complement receptor. In conclusion, the size of liposomes affected complement recognition, and the liposomes were taken up by the liver depending on the extent of opsonization. PMID- 8008709 TI - Hydrogen bonding potential as a determinant of the in vitro and in situ blood brain barrier permeability of peptides. AB - With the exception of various central nervous system (CNS)-required nutrients for which specific, saturable transport systems exist, the passage of most water soluble solutes through the blood-brain barrier (BBB) is believed to depend largely on the lipid solubility of the solutes. Most peptides, therefore, do not enter the CNS because of their hydrophilic character. Recently, utilizing homologous series of model peptides and Caco-2 cell monolayers as a model of the intestinal mucosa, it was concluded that the principal determinant of peptide transport across the intestinal cellular membrane is the energy required to desolvate the polar amide bonds in the peptide (P. S. Burton et al., adv. Drug Deliv. Rev. 7:365, 1991). To determine whether this correlation can be extended to the BBB, the permeabilities of the same peptides were determined using an in vitro as well as an in situ BBB model. The peptides, blocked on the N- and C terminal ends, consisted of D-phenylalanine (F) residues: AcFNH2, AcF2NH2, AcF3NH2, AcF2(NMeF)NH2, AcF(NMeF)2NH2, Ac(NMeF)3NH2, and Ac(NMeF)3NHMe. A good correlation among the permeabilities of these model peptides across the bovine brain microvessel endothelial cell (BBMEC) monolayers, an in vitro model of the BBB, and their permeabilities across the BBB in situ was observed (r = 0.928, P < 0.05). The permeabilities of these peptides did not correlate with the octanol buffer partition coefficients of the peptides (r = 0.389 in vitro and r = 0.155 in situ; P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8008708 TI - Stereospecific distribution of methylphenidate enantiomers in rat brain: specific binding to dopamine reuptake sites. AB - To investigate the stereoselective distribution of methylphenidate (MPD) enantiomers in rats, the concentrations of each enantiomer were determined in plasma and brain regions (cerebellum, striatum, basal forebrain, brain stem, and cortex) after iv administration of racemic MPD and its individual enantiomers. The concentrations of MPD enantiomers in each brain region reached pseudo-steady state within 10 min after iv administration of racemic MPD (2 mg/kg dose). The influx clearances for MPD calculated from Kpapp values in each brain region were not significantly different between MPD enantiomers and between the five brain regions. The mean Kpapp values for (+)-MPD in the striatum at 120 and 240 min after administration of racemic MPD were 10.1 and 10.5, respectively, and these values at each time were significantly larger than the Kpapp values (7.5 and 7.0, respectively) for the (-)-isomer (P < 0.01). The Kpapp value for (+)-MPD in the striatum decreased by coadministration of mazindol as an inhibition of both dopamine and norepinephrine reuptake, but it was not changed by desipramine as a norepinephrine reuptake inhibitor. These results suggest that (+)-MPD was bound specifically to the dopamine reuptake site in the striatum. PMID- 8008710 TI - Accumulation kinetics of propranolol in the rat: comparison of Michaelis-Menten mediated clearance and clearance changes consistent with the "altered enzyme hypothesis". AB - (+)-Propranolol was infused at two rates into the pyloric vein (a portal vein tributary) of 15 male Sprague Dawley rats until apparent steady-state conditions were established (i.e., 8 hr at each rate). One group (n = 7) received the high dose (40 micrograms/min/kg) first, and in the other group (n = 8) the low dose (20 micrograms/kg/min) was used to initiate treatment. Free and total serum concentrations of propranolol were measured. When the low dose was given first, the apparent steady-state concentrations achieved during low- and high-rate infusion steps were 166 +/- 37 and 774 +/- 235 ng/mL, respectively. These data are consistent with a simple Michaelis-Menten kinetic model and the key parameters of such a model (Vmax and Km) were estimated. However, a crucial test of such a model (and one which should give insight regarding the relevance of an "altered enzyme hypothesis") is to reverse the order of infusion steps since, in a system controlled by Michaelis-Menten kinetics, the same steady-state concentrations should be achieved regardless of the order in which infusion steps are given. When the sequence of infusion rates was reversed, steady-state concentrations were 492 +/- 142 and 298 +/- 79 ng/mL for the high and low infusion rates, respectively. Clearly, a history of high-dose exposure reduces the intrinsic clearance of total drug (CLss) during a subsequent low-dose exposure (i.e., the apparent steady-state levels during the low-dose pyloric vein infusions were significantly different; P < 0.001). When these data were corrected for plasma protein binding, the same trends emerged.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8008711 TI - Pharmacokinetics and pharmacodynamics of L-703,014, a potent fibrinogen receptor antagonist, after intravenous and oral administration in the dog. AB - The pharmacokinetics and pharmacodynamics of L-703,014, a fibrinogen receptor antagonist, have been examined in the dog. An analytical method which utilizes methanol precipitation of dog plasma proteins followed by HPLC with an automated column switching technique using the chemical analogue L-704,326 as internal standard was developed for the determination of L-703,014 in dog plasma. The compound was not metabolized in the dog and was eliminated in the kidneys and into bile. Of the administered dose, 68.9 +/- 1.3% (i.v.) and 80.5 +/- 11.9% (p.o.) were recovered in the feces; 20.3 +/- 1.3% (i.v.) and 2.2 +/- 0.2% (p.o.) were recovered in the urine by 72 hr. L-703,014 was 23 +/- 3.4% bound in dog plasma protein and the mean ratio of plasma/whole blood was 1.22 +/- 0.05. The mean terminal half-life was 118 +/- 36 min, the mean steady-state volume of distribution was 0.61 +/- 0.22 L/kg, and the mean plasma clearance was 8 +/- 2 mL/min/kg. Ex vivo platelet aggregation measurements were made by inducing platelet aggregation with 10 micrograms/mL collagen in the presence of 1 microM epinephrine as an agonist. The mean C50 was 44.4 +/- 6.0 ng/mL, and the mean Hill coefficient was 1.5 +/- 0.3. The mean bioavailability was 4.9 +/- 1.4% in dogs administered 2.0 mg/kg (p.o.). PMID- 8008712 TI - Site-differential gastrointestinal absorption of benazepril hydrochloride in healthy volunteers. AB - The absorption of benazepril-HCl (BZPH), an orally active angiotensin-converting enzyme (ACE) inhibitor, in various regions of the gastrointestinal (GI) tract was investigated using an intestinal intubation technique. Thirteen subjects completed this single-dose, three-phase sequential crossover study. The drug (20 mg) was administered either as a 4-hr colonic infusion (COLON) or as a small intestinal infusion (SI) in the first two phases and as an oral bolus solution (ORAL) in the third phase, with a 2-week washout between each treatment. Serial plasma and urine samples were collected for up to 4 days after dosing. BZPH and its active metabolite benazeprilat (BZPL) were determined using a gas chromatography/mass spectrometry method. BZPH was absorbed rapidly into the bloodstream (Tmax = 0.5 hr after ORAL). Absorption was also rapid for SI, with a postinfusion half-life (0.57 hr) nearly identical to that for ORAL (0.59 hr). The absorption rate after COLON was much slower (lower Cmax and longer Tmax) compared to that after SI, and the apparent half-life (1.7 hr) was prolonged. SI delivered 90%, whereas COLON delivered 23%, of the drug into the systematic circulation as compared to ORAL. BZPL was rapidly formed upon drug absorption. The metabolite-to drug AUC ratios were comparable for SI and ORAL (8.9 vs 9.7), indicating that first-pass metabolism of BZPH was neither saturable nor input rate dependent. The metabolite-to-drug AUC ratio was reduced for COLON (5.0), indicating that the mechanism of absorption of BZPH in the colon may be different than that after SI and ORAL. Urinary recovery data were consistent with plasma data.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8008714 TI - Quantification and visualization of the transport of octreotide, a somatostatin analogue, across monolayers of cerebrovascular endothelial cells. AB - Confocal laser scanning microscopy (CLSM) was used to quantify and visualize the transport of the octapeptide and somatostatin analogue, octreotide (SMS 201-995, Sandostatin), across monolayers of bovine cerebrovascular endothelial cells, an in vitro model of the blood-brain barrier. The concentrations of octreotide and its conjugates in the cell culture medium were determined by radioimmunoassay (RIA). Two fluorescent conjugates of octreotide (FITC- and NBD-octreotide) were used to obtain CLSM images. The peptides did not undergo significant degradation in the presence of brain endothelial cell monolayers. The transport rate of octreotide expressed as clearance (Cl) and endothelial permeability (Pe) did not depend on either the initial concentration (between 10 nM and 1 microM) or the site of administration (luminal or abluminal side of the monolayer), indicating the absence of saturable and/or asymmetrical transport mechanisms. The Pe of octreotide and that of the paracellular permeability marker fluorescein correlated well. Although the conjugates are more lipophilic than octreotide itself, they exhibited lower Cl and Pe, values probably because of their larger molecular size. On the CLSM images, FITC-octreotide was present only in the intercellular space, while the cells did not exhibit detectable fluorescence. Transport studies and CLSM images suggest that octreotide passes the endothelial monolayer primarily via the paracellular route without significant contribution of carrier-mediated transport. PMID- 8008713 TI - Dose-dependent pharmacokinetics of L-693,612, a carbonic anhydrase inhibitor, following oral administration in rats. AB - The disposition of L-693,612, a carbonic anhydrase inhibitor, was examined in rats following oral doses of 0.05 to 25 mg/kg. Area under the blood concentration time curve (AUC) increased linearly with dose up to 0.25 mg/kg. However, the linear range did not extend to 5 and 25 mg/kg doses; AUC rose only 10-fold overall despite a 500-fold increase in dose. A similar pattern of disproportionality occurring after i.v. administration indicated that the nonlinear behavior after oral doses was not due to dose-limited absorption, but rather it arose because blood clearance increased with dose. Concentration dependent erythrocyte/plasma partitioning arising from saturation of binding to erythrocyte carbonic anhydrase could explain the dose-dependent blood clearance. At blood concentrations (< 25 microM) achieved in the linear dose range, L 693,612 was extensively sequestered in red blood cells, bound to carbonic anhydrase, with a constant low free fraction in plasma available for elimination. At doses which saturated the binding capacity of carbonic anhydrase, blood clearance increased, since for low hepatic extraction compounds, the rate of elimination is dependent upon the free fraction in blood. Dose-dependent increases in distribution volumes were consistent with the view that high affinity binding to carbonic anhydrase confined this compound largely to blood volume at low doses, but saturation of binding sites increased availability to peripheral tissues after high doses. Increasing the dose had a minimal effect on terminal half-life because it reflected the concentration-time profile during a period of linear distribution into erythrocytes. PMID- 8008715 TI - Analytical chiral separation of the stereoisomers of a novel carbonic anhydrase inhibitor and its deethylated metabolite, and the assignment of absolute configuration of the human metabolite and chiral degradation products. AB - Several approaches to the separation of four stereoisomers, 1-4, of a novel, topically active, carbonic anhydrase inhibitor, 1, with two chiral centers in the molecule and four isomers, 5-8, of its chiral metabolite, 5, were evaluated. These methods include nonchiral derivatization followed by separation on chiral stationary phases (CSPs) and chiral derivatization and separation on nonchiral columns and on CSPs. Baseline separation of stereoisomers 1-4 was achieved in less than 15 min after chiral derivatization with (S)-(+)-1-(1-naphthyl)ethyl isocyanate (NEIC) and chiral chromatography on a (R)-N-(3,5-dinitrobenzoyl)phenyl glycine (DNBPG) column under normal phase (NP) conditions. Similarly, isomers 5-8 were baseline separated in less than 20 min after derivatization with NEIC and chromatography on nonchiral (nitrophenyl) and chiral [(S)-(3,5 dinitrobenzoyl)leucine; DNBL] columns in series under the same NP chromatographic conditions. Only partial separation of the diastereomeric derivatives was observed on a variety of nonchiral columns. In addition, all other direct and indirect chiral separation approaches gave only partial separation of at least two stereoisomers within the group of 1-4 or 5-8. The details of chiral separations using various methods and separation (alpha) and capacity factors (k') of the derivatized isomers 1-8 on a series of chiral and nonchiral columns are presented. Using these methods, the absolute configuration of the human metabolite of 1 was established as S1S2 (5), and the heat (HD) and light (LD) degradation products of 1 as R1S2 (3) and S1S2 (5), respectively. PMID- 8008716 TI - Novel stabilizing method for antisense oligodeoxynucleotides. PMID- 8008717 TI - 1H-NMR and 13C-NMR spectral assignments of spiramycins I and III. PMID- 8008718 TI - Rapid synthesis of 3-[18F]fluoro-1-(2'-nitro-1'-imidazolyl)-2-propanol ([18F]fluoromisonidazole). PMID- 8008719 TI - Low dose acetylsalicylic acid in the antithrombotic treatment of patients with stable angina pectoris and acute coronary syndromes (unstable angina pectoris and acute myocardial infarction). AB - Acetylsalicylic acid has an antithrombotic effect by inhibition of thromboxane A2 synthesis in platelets. Thromboxane A2 is a potent stimulator of platelet aggregation and vasoconstriction and synthesis may be completely inhibited by a single oral dose of 150 mg acetylsalicylic acid or an intravenous dose of 100 mg. A daily maintenance dose of 75 mg acetylsalicylic acid is sufficient to effectively inhibit thromboxane A2 synthesis in long-term treatment. Acetylsalicylic acid therapy reduces acute myocardial infarction and sudden death in patients with stable angina pectoris and the drug is equally effective in patients with symptomatic and 'silent' angina pectoris. Early intervention with acetylsalicylic acid in patients with unstable angina pectoris reduces the risk of acute myocardial infarction and death. In patients with acute myocardial infarction, acute therapy with acetylsalicylic acid significantly reduces mortality both in monotherapy and in combination with thrombolytics. In the secondary prophylaxis following acute myocardial infarction, acetylsalicylic acid reduces the incidence of reinfarction and coronary death. Treatment of 100 patients with acute coronary syndrome (unstable angina pectoris or acute myocardial infarction) for 2 years may hinder the development of 3-4 fatal and 4 non-fatal vascular events. The risk of gastrointestinal side-effects and bleeding during acetylsalicylic acid therapy is dose-dependent and the incidence is low with a daily dose of 75-150 mg. PMID- 8008720 TI - The cardiovascular effects of ricin in rabbits. AB - Ricin is a toxic lectin from the castor bean. The time course of its toxic effects on the cardiovascular system of rabbits was investigated after determining its LD50 and minimum lethal dose in rabbits by the Up and Down method, as a basis for dosing. Systolic and diastolic arterial pressures, electrocardiogram and heart rate were recorded for 48 hr following administration of either a toxic sublethal (0.22 microgram/kg) or minimum lethal dose (0.44 microgram/kg) of ricin. After a delayed onset of about 20 hr, the minimum lethal dose (0.44 microgram/kg) of ricin caused a significant decrease in both systolic and diastolic pressures (P < 0.05). The systolic and diastolic pressures decreased 0.47 and 0.39 mmHg/hr more so than control groups, respectively. A toxic sublethal dose (0.22 microgram/kg) of ricin did not significantly alter either systolic or diastolic pressure. Neither dose of ricin caused cardiac arrhythmias or significantly increased heart rate. We conclude that the lethal hypotensive sequelae of ricin toxicity in the rabbit were peripheral in origin and not cardiogenic at these two doses. PMID- 8008721 TI - Atrial natriuretic peptide and cyclic guanosine-3'5'-monophosphate in hypertensive pregnancy and during nifedipine treatment. AB - Atrial natriuretic peptide exhibits natriuretic, diuretic and vasodilatory properties. We compared plasma concentrations of atrial natriuretic peptide, cyclic guanosine-3',5'-monophosphate (cGMP), electrolytes and urinary excretion of cGMP and electrolytes in hypertensive pregnant women to those in normotensive pregnant and normotensive non-pregnant women. Plasma atrial natriuretic peptide concentrations in hypertensive pregnant and normotensive non-pregnant women were equal, whereas in normotensive pregnant women it was lower (P < 0.05), than in non-pregnant. Urinary cGMP excretion was higher in both normotensive and hypertensive pregnant than in non-pregnant women (P < 0.01), whereas plasma cGMP levels were similar. A five-day nifedipine treatment (10 mg t.i.d.) had no effects on any of the variables. In hypertensive pregnancy, a reduction of systolic blood pressure by nifedipine correlated with the initial plasma atrial natriuretic peptide (P < 0.05) and a decrease in diastolic blood pressure with the initial plasma cGMP concentration (P < 0.05). The results of this small material suggest that plasma atrial natriuretic peptide concentration predicts the response to nifedipine in hypertensive pregnancy. However, the atrial natriuretic peptide-cGMP system does not seem to mediate the antihypertensive effect of nifedipine, while plasma atrial natriuretic peptide remained unaltered. Increased urinary cGMP excretion in both pregnant groups but lowered plasma atrial natriuretic peptide in normotensive pregnancy suggest other factors than circulating atrial natriuretic peptide to promote renal cGMP excretion during pregnancy. PMID- 8008722 TI - Effect of methyl mercury exposure on the uptake of radiolabeled inorganic mercury in the brain of rabbits. AB - Exposure to mercuric compounds at high dose levels has previously been shown to alter the integrity and function of the blood-brain barrier in laboratory animals. In the present study, we have investigated the distribution of intravenously administered inorganic 203Hg in rabbits additionally exposed to MeHg. A single dose of 203HgCl2 was administered together with or 5 min. or 24 hr after administration of a single dose (10 or 37.5 mumol/kg b.wt.) of MeHg. In another experiment, 203HgCl2 was administered to rabbits subchronically exposed to MeHg (1 mumol/kg b.wt. daily for three weeks) 24 hr after cessation of treatment. The integrity of the blood-brain barrier was assayed by measuring the uptake of 203Hg in the brain, as the blood-brain barrier usually serves to exclude inorganic Hg from the brain. The concentration of 203Hg within the brain was similar in all MeHg-treated rabbits, corresponding to 0.02% of the administered dose, and not different from that of control animals. Under these conditions, no obvious damage to the blood-brain barrier by MeHg could be observed. PMID- 8008723 TI - Arterial smooth muscle responses in adult and moderately aged spontaneously hypertensive rats. AB - In order to further clarify differences between spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto (WKY) rats as well as the effects of ageing, vascular smooth muscle responses of mesenteric arterial rings and intracellular free calcium concentration ([Ca2+]i) in platelets and lymphocytes were studied in 20-week-old and 32-week-old animals. Arterial contractile responses induced by noradrenaline and potassium chloride were comparable in 20-week-old SHR and WKY rats, whereas at 32 weeks of age maximal contractile force generation to both of these agents was clearly lower in SHR. In both age groups the calcium entry blocker nifedipine was more effective in inhibiting potassium chloride-evoked responses in SHR than in WKY rats, and arterial relaxation responses by endothelium-dependent (acetylcholine) and endothelium-independent (nitroprusside, isoprenaline) mechanisms were more pronounced in WKY rats when compared with SHR. The ability of vascular smooth muscle cells to sequester calcium was evaluated by first depleting cellular calcium stores with maximal contractions to noradrenaline in calcium-free buffer, whereafter calcium was returned to the organ bath. After a 10 min. calcium loading period the arterial rings were rechallenged with noradrenaline. Both in 20-week-old and 32-week-old rats these responses were less marked in SHR than in WKY rats, suggesting reduced ability of smooth muscle cells to sequester calcium. In addition, platelets and lymphocytes were used as cell models to examine [Ca2+]i in the experimental groups by the fluorescent indicator quin-2. In these two cell types [Ca2+]i was higher in SHR than in WKY rats in both of the age groups studied.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8008724 TI - The metabolism of mebeverine in man: identification of urinary metabolites by gas chromatography/mass spectrometry. AB - The urinary metabolites of orally administered mebeverine hydrochloride (270 mg) were studied in five healthy volunteers with the aid of gas chromatography/mass spectrometry. Mebeverine, which is an ester of veratric acid and 4-(ethyl-[2-(4 methoxyphenyl)-1-methylethyl]amino)butan-1-ol, was completely hydrolysed to the corresponding acid and alcohol moieties. The acid moiety was subsequently O demethylated to vanillic acid and isovanillic acid, which in turn were further O demethylated to protocatechuic acid. The alcohol moiety was O-demethylated to the corresponding phenol 4-(ethyl-[2-(4-hydroxyphenyl)-1-methylethyl]amino)butan-1 ol. In 24 hr, 44% of the dose was accounted for as follows: Veratric acid 32%, vanillic acid 2.7%, isovanillic acid 6.5%, 4-(ethyl-[2-(4-methoxyphenyl)-1 methylethyl]amino)butan-1-ol 0.9% and 4-(ethyl-[2-(4-hydroxyphenyl)-1 methylethyl]amino)butan-1-01 2.1%. Only trace amounts of protocatechuic acid were found in the urine. The results indicated that the metabolites were mostly excreted as conjugates. The total excretion of the acid moiety, unchanged or in the form of metabolites was 97.6%. The corresponding value for the alcohol moiety was 5.5%. PMID- 8008725 TI - Should probenecid be used to reduce the dicloxacillin dosage in orthopaedic infections? A study of the dicloxacillin-saving effect of probenecid. AB - Reduction in the dosage of dicloxacillin from 500 mg to 250 mg 3 times a day would mean lowering of costs and less side-effects in orthopaedic infections. In this cross-over study, the serum concentrations of dicloxacillin were measured in 9 patients after administration of dicloxacillin 500 mg 3 times a day (dicloxacillin 500 mg) and after co-administration of 250 mg dicloxacillin and 250 mg probenecid 3 times per day (dicloxacillin 250 mg+probenecid 250 mg). Concentrations were measured every hour after the tablet intake. The mean maximum serum concentrations of dicloxacillin were 17.1 micrograms/ml (dicloxacillin 500 mg) and 12.2 micrograms/ml (dicloxacillin 250 mg+probenecid 250 mg), respectively (P < 0.05). Serum concentrations above 3 micrograms/ml were obtained during 285 min. in both regimes, but the individual variations were biggest during in the dicloxacillin 250 mg+probenecid 250 mg treatment. Serum concentrations above 5 micrograms/ml were in mean measured during 228 min. (dicloxacillin 500 mg) and 190 min. (dicloxacillin 250 mg+probenecid 250 mg), respectively (P < 0.05). The clinical significance of these findings is being discussed. In theory, treatment with dicloxacillin 250 mg+probenecid 250 mg may be as sufficient as dicloxacillin 500 mg. PMID- 8008726 TI - Effect of 8-hydroxy-, 8-mercapto- and 5-chloro-7-iodo-8-hydroxy-quinoline on the uptake and distribution of nickel in mice. AB - Oral administration of Ni2+ together with 8-hydroxyquinoline (8-OH-quinoline), 8 mercaptoquinoline (8-SH-quinoline) or 5-chloro-7-iodo-8-hydroxyquinoline (clioquinol) resulted in increased tissue levels of the metal in several tissues of mice in comparison with animals given the Ni2+ alone. Ni2+ forms lipophilic complexes with these compounds and it can be assumed that this will facilitate the uptake of the Ni2+ over the walls of the gastrointestinal tract. Our results showed that 8-SH-quinoline, in contrast to 8-OH-quinoline and and clioquinol, induces a markedly changed distribution pattern of the Ni2+ in the body, with uptake of the metal in tissues such as the central nervous system, pigmented tissues, the pancreatic islets and the thyroid. It is probable that the Ni(2+) complex with 8-SH-quinoline is stable enough to persist for a time period in the tissues and that the obtained pattern partly reflects the distribution of the complexed metal. In contrast, following the absorption from the gastrointestinal tract there may be a dissociation of the complexes between Ni2+ and 8-OH quinoline or clioquinol, resulting in increased metal levels in various tissues, but with similar distribution as when the Ni2+ is given alone. PMID- 8008727 TI - Expression of the interferon-gamma receptor gene in mouse placentas is related to stage of gestation and is restricted to specific subpopulations of trophoblast cells. AB - In order to evaluate the potential of placental cells to bind the multifunctional cytokine, interferon-gamma (IFN-gamma), tissues collected from pregnant Swiss mice were analysed for IFN-gamma receptor (IFN-gamma R) mRNA and protein. Northern blot hybridization studies indicated that the relative abundance of IFN gamma R mRNA increased as gestation progressed to term. Analysis by in situ hybridization revealed that trophoblast cells first contained high steady state levels of IFN-gamma R mRNA at g.d. 12. At g.d. 12 and 14, transcription was restricted to cells in the spongiotrophoblast region and nests of similar cells in the labyrinthine region. These cells also contained immunoreactive IFN-gamma R protein. By g.d. 18, IFN-gamma R mRNA was clearly detectable in large spongiotrophoblast cells and labyrinthine trophoblast. IFN-gamma R mRNA was low to absent in giant trophoblast cells at all stages of gestation. Specific mRNA was present in parietal and visceral yolk sac cells by g.d. 14. Thus, expression of the IFN-gamma R gene in mouse placental cells is influenced by stage of gestation, cell lineage and state of differentiation. Whether or not these cells respond vigorously to IFN-gamma with induction of antiviral proteins, increased MHC class I antigens and growth modulation may therefore be determined by their expression of specific receptors for this pluripotent cytokine. PMID- 8008728 TI - Paternal and maternal major histocompatibility complex class I antigens are expressed co-dominantly by equine trophoblast. AB - Invasive equine trophoblast cells of the chorionic girdle express high levels of paternally inherited Major Histocompatibility Complex (MHC) class I antigens prior to migration into the endometrium to form the so-called endometrial cups. Three groups of experiments were performed to determine if maternally inherited MHC class I antigens are expressed on chorionic girdle cells. Results indicated that maternally and paternally inherited MHC class I antigens are co-dominantly expressed by cells of the invasive equine trophoblast, and therefore, that the expression of polymorphic equine MHC class I genes does not appear to be affected by genomic imprinting in this tissue. The demonstration that cells of the chorionic girdle were immunogenic supports the hypothesis that invasion of the maternal endometrium by chorionic girdle cells stimulates the production of anti paternal alloantibodies normally observed in early horse pregnancy. The co dominant expression of MHC class I antigens by invasive chorionic girdle cells has important implications for the mechanism of recognition of allogeneic fetal MHC class I antigens by the maternal immune system. PMID- 8008730 TI - ATP independent calcium transport and binding by basal plasma membrane of human placenta. AB - The transport of large amounts of Ca2+ by the plasma membranes of human placental syncytiotrophoblast is essential to the mineralization of the growing fetal skeleton. We have investigated transport by the basal (fetal-facing) plasma membrane (BPM). Ca2+ was taken up by purified BPM vesicles in a time-dependent manner and equilibrium attained in approximately 60 min. The apparent equilibrium space was many fold higher than that determined using other substrates (e.g. leucine), suggesting that Ca2+ is concentrated or bound within the vesicles. The more rapid uptake and exit in the presence of A23187 indicates that membrane transport is rate limiting and that Ca2+ is internalized within the membrane space. The initial rate of uptake was approximately by measurement during the first 2 s of incubation. Concentration dependence data were fit to a Michaelis Menten model with one saturable site and diffusion (Km = 12 microM; Vmax = 4 nmol/min/mg; KD = 39 nmol/min/mg/mM). Saturable Ca2+ binding (Kd = 16 microM; Bmax = 3.4 nmol/mg) was of lower capacity than previously observed for microvillous membrane. PMID- 8008729 TI - Riboflavin uptake in microvillous and basal membrane vesicles isolated from full term human placentas. AB - Riboflavin uptake was characterized using membrane vesicles isolated from the apical (maternal-facing) and basal (fetal-facing) membranes of the syncytiotrophoblast from full-term human placentas. Equilibrium [3H]riboflavin uptake was insensitive to variations in incubation medium osmolarity in contrast to [3H]alanine uptake into an osmotically sensitive space. Osmotic insensitivity suggested riboflavin binding to a membrane component. The dissociation constant of riboflavin binding was similar in microvillous (Kd = 2 microM) and basal membrane vesicles (Kd = 1 microM). Binding capacity was significantly higher in microvillous membranes (Bmax = 11.9 pmol/mg protein). The relatively high affinity binding to the membrane vesicles may represent a first step in riboflavin transport. PMID- 8008731 TI - Characterization of cofactor activity for factor I: cleavage of complement C4 in human syncytiotrophoblast microvilli. AB - To coexist with complement, human tissues express membrane-integrated regulatory proteins that inhibit the activity of autologous complement on cell surfaces. Certain of these complement regulatory proteins act as obligatory cofactors for proteolytic inactivation of activated C4(C4b) by factor I. Extraembryonic tissues and in particular trophoblasts constitute an interface at risk from maternal complement during pregnancy. The present study examined syncytiotrophoblast plasma membrane (STM) cofactor activity for cleavage of immobilized methylamine treated complement component C4(C4ma), a C4b analog by factor I. Membrane cofactor protein (MCP or CD46) provided most of the cofactor activity in STM preparations. Minor cofactor activity was derived from C4 binding protein that was firmly bound to STM. Cofactor activity for cleavage of C4ma at its two sites for factor I was enhanced at higher concentrations of STM and at lower concentrations cleavage at a C terminal site predominated. Soluble cofactor activity was present in STM preparations and was provided by 65 KDa, 55 KDa and 50 KDa soluble species of MCP that lacked amphiphilic properties. These results are consistent with a major role for MCP in regulation of C4 activity on the maternal-facing surfaces of extraembryonic tissues during human development. Soluble MCP may provide additional fluid phase complement regulatory activity in the maternotrophoblastic zone. PMID- 8008732 TI - Pinocytosis in the rat visceral yolk sac: potential role in amino acid nutrition during the fetal period. AB - At 9.5 to 10.5 days post-conception (p.c.) the rat embryo receives amino acids primarily by pinocytosis of maternal proteins by the visceral yolk sac (VYS) endodermal cells and their subsequent digestion in lysosomes. As this mechanism may also contribute to the nutritional support of the rapidly growing fetus later in gestation, this study determines the potential of the VYS to contribute to the amino acid needs of the rat fetus on 13.5, 15.5 and 17.5 days p.c. Wistar rats were killed on 11.5, 13.5, 15.5, 17.5 and 19.5 days p.c. and the protein content of fetuses, VYSs and serum was determined. Additional VYSs were isolated on the same days p.c. and the uptake of [14C]sucrose, a measure of fluid-phase pinocytosis, was determined. The rate of protein accretion by the fetus and the capacity of the VYS to pinocytose and digest proteins were calculated on 13.5, 15.5 and 17.5 days p.c. There was a decrease in pinocytic capacity, per mg protein, over the period of development studied but, owing to the growth of the tissue, the total capacity of the yolk sac to pinocytose and digest proteins increased from 13.5 to 17.5 days p.c. Comparison of the VYSs capacity to pinocytose and digest proteins and the rate of protein accretion by the fetus suggests that the VYS could support a significant proportion of the increase in protein content of the growing fetus. This conclusion is reinforced by the limited capacity of the maternal plasma to supply free amino acids to the fetus.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8008733 TI - A morphometric approach to the relation of karyotype, gestational age and histological features in early spontaneous abortions. AB - Previous studies revealed that chorionic villus size and proliferation of trophoblast were of little value as predictors of chromosomal abnormality. Since these findings might be due to the known intra- and inter-observer variation in histological assessments of early placentae, objective measurement of features might be more valuable to predict abnormal karyotype. Also, gestational age might influence structural development of villi in different karyotypes in a variable way, obscuring a possible relationship between features and karyotype. We, therefore, quantified villus size composed of stromal and trophoblastic tissues in 82 placentae using the point counting method and related the results to karyotype and gestational age. At the group level there appeared to be no difference in the median mean cross-sectional villus-, stromal and trophoblastic area, trophoblast/stroma ratio and trophoblastic thickness between chromosomally normal and abnormal placentae. Of the abnormal placentae only triploid placentae showed areas larger than normal and other abnormal placentae. In respect of gestational age villous profile area increased with age in triploid placentae, but decreased in trisomic abortions. At the individual case level parameter values outside the 'normal' range appeared to be rather insensitive, but highly specific for the prediction of karyotypic aberrations, again mainly triploidy. PMID- 8008734 TI - Quantitative comparison of prolactin production by decidua compacta and spongiosa from the first trimester elective termination of pregnancy. AB - Prolactin (PRL) producing capacity was studied in explants of decidua compacta and decidua spongiosa obtained from 41 patients undergoing termination of pregnancy at gestation 6 to 12 weeks. In vitro PRL producing capacity, expressed as mIU/g protein, of the decidua compacta was significantly higher (P < 0.05) than those of decidua spongiosa. Production of PRL increased with gestation from 6 to 12 weeks with a more rapid rate at the later gestation. The pattern of increase fitted significantly (P < 0.0001) to the exponential model for both decidua compacta and decidua spongiosa. The exponential regression equations for decidua compacta and decidua spongiosa were (ln y = 4.25 + 0.19x) and (ln y = 2.80 + 0.31x) respectively. Hence, although both decidua compacta and decidua spongiosa had a similar pattern of increase in PRL production, the rate of increment was significantly greater in decidua spongiosa than in decidua compacta. These findings suggest that separating decidua compacta and decidua spongiosa of the first trimester would reduce the heterogeneity of decidual tissue and offer a new approach to the studies of the synthesis, release and regulation of PRL production by human decidua. PMID- 8008736 TI - Relationship of nuclear DNA content to clinicopathologic features in colorectal cancer. AB - Nuclear DNA content was determined in 123 colorectal adenocarcinomas by flow cytometry using multiple frozen tumor samples. Thirty-three (26.8%) carcinomas were classified as diploid and 90 as aneuploid (73.2%). Presence of DNA aneuploidy was found to be unrelated to tumor stage and grade of differentiation and to other histopathological variables such as pattern of growth, degree of peritumoral lymphocytic infiltration, and venous invasion. However, multiploid tumors (20/123, 16.3%) were more frequently noted in advanced stages of disease (Stages III and IV, P < 0.025) and more often showed unfavorable histopathological features, especially an infiltrating pattern of growth (P < 0.05), compared with diploid and single aneuploid carcinomas. Nuclear DNA content was found to be closely related to tumor site. Carcinomas of the proximal (right and transverse) colon were more frequently diploid (19/43, 44.2% versus 14/80, 17.5%--P < 0.005) and more often displayed a DNA index (DI, defined as the ratio of the DNA content of neoplastic cells to that of normal cells) < or = 1.20 (27/43, 62.8% versus 19/80, 23.7%--P < 0.001) than did tumors localized distally to the splenic flexure. Nuclear DNA content was also found to be related to tumor type. A high proportion of mucinous adenocarcinomas showed DI values < or = 1.20 (14/21, 66.7%); conversely only 32 of 102 (31.4%) non-mucinous adenocarcinomas had a DI < or = 1.20 (P < 0.01). The nuclear DNA content of mucinous adenocarcinomas seemed to be independent of tumor location.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8008735 TI - Placental morphogenesis and the star volumes of villous trees and intervillous pores. AB - In 27 human placentae collected at 13-39 weeks, the growth and morphogenesis of villi and of the maternal intervillous space were assessed using a design-based stereological approach for estimating star volume. The purpose was to quantify changes occurring during these processes and to derive parameters pertinent to physiological performance (notably transport capability and haemodynamics). Placentae were sampled by cutting paraffin sections at random locations and orientations. Estimates of the global volumes of peripheral (terminal and intermediate) villi and intervillous space were derived from placental volumes via point counting. Total villous surface was estimated by intersection counting and length by transection counting. Treating villi like the branches of tree-like networks and the intervillous space as a system of confluent pores, estimates of the star volumes of these compartments were also made. These volumes were calculated by measuring point-sampled intercept lengths. The total volumes of villi and intervillous space increased steadily throughout gestation. After the second trimester, the increase in volume of villi was accompanied by a decrease in villous star volume. This can be explained by the continued elaboration and maturation of terminal villi, the combined length of which increased whilst mean diameter declined. The star volume of the intervillous space also declined and this, too, is consistent with villous growth and proliferation. PMID- 8008737 TI - Naked megakaryocyte nuclei in bone marrows of patients with acquired immunodeficiency syndrome: a somewhat specific finding. AB - Naked megakaryocyte nuclei (NMN) were studied retrospectively in 100 bone marrow biopsy sections and aspirates from patients with acquired immunodeficiency syndrome (AIDS) and 124 non-AIDS controls. An NMN score was developed to semiquantitate the NMN. The AIDS bone marrows had an incidence of 97% and a mean NMN score of 2.24 which was a higher incidence and score than the control groups and was statistically significant. The control groups consisted of 20 chronic myeloproliferative disorders (incidence of 70% and score of 1.4); 24 cases of acute myelogenous leukemia and myelodysplastic syndrome (incidence of 29.2% and 0.46 score); 22 cases of non-AIDS immune thrombocytopenic purpura (incidence of 50% and 0.82 score); 11 cases of acute lymphocytic leukemia (0% incidence); 21 cases of anemia (52.4% incidence and 0.7 score); and 26 cases of lymphoma staging (35% incidence and 0.35 score). It is concluded that NMN are a very frequent and, with a high score, a specific finding in AIDS bone marrow examinations. PMID- 8008739 TI - Histochemical and biochemical aspects of lectin binding glycoproteins in primary and metastatic adenocarcinoma in the lung. AB - It is often difficult to differentiate between primary adenocarcinoma and metastatic adenocarcinoma in the lung. At least three lectins-peanut treated with neuraminidase, Ricinus communis-I and succinylated wheat germ-showed highly positive glycoprotein binding pattern along the plasma membrane of primary and metastatic adenocarcinoma in the lung. In order to distinguish primary pulmonary adenocarcinoma from metastatic adenocarcinoma in the lung with the three lectins, 40 pulmonary adenocarcinomas, seven extrapulmonary metastatic adenocarcinomas, and 16 metastatic adenocarcinoma in the lung were studied. Extracts from fresh tissue homogenate, after fractionation by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, were transferred by Western blotting and stained with lectin, and the lectin-bound glycoconjugates were read by a densitometer. The results showed all three lectin-bound glycoconjugate of primary pulmonary adenocarcinoma cases to be concentrated at about 200 Kd, but those of normal lung tissue had different molecular weights. Metastatic adenocarcinoma in the lung had lectin-bound glycoconjugate of about 120 Kd as well as 200 Kd. The amount of lectin binding high molecular weight substance was lower in metastatic adenocarcinoma in the lung than in primary pulmonary adenocarcinoma, especially succinylated wheat germ (P < 0.001). Therefore, decreased expression of the lectin binding high molecular weight glycoprotein may be a biochemical change associated with metastatic potential. PMID- 8008738 TI - Role of DNA content determination by image analysis in confirmation of dysplasia in Barrett's esophagus. AB - Progression to cancer in Barrett's esophageal columnar metaplasia is classically heralded by the presence of epithelial dysplasia. Differentiation of reactive epithelial atypia and mild dysplasia from severe dysplasia, however, may often be difficult especially with limited biopsy material. We performed DNA content analysis of 11 cases of Barrett's esophagus showing variable reactive atypia, 24 cases of Barrett's with low- and high-grade dysplasia, and 30 cases of Barrett's with invasive adenocarcinoma (BCA) using Feulgen-stained paraffin sections and the CAS 200 image analyzer. The mean DNA index of the uniformly diploid BE was 1.06. The 1.26 mean DNA index for the low-grade Barrett's esophagus with dysplasia, 1.62 for high grade, and 1.88 DI for BCA were significantly greater than for variable reactive atypia (P < 0.004) but not different from each other. Six BCA cases (20%) were diploid; 24 cases (80%) were aneuploid. Mean survival of diploid BCA at 20.4 mo was nearly double the survival of 10.6 mo for aneuploid BCA. However, this difference was not statistically significant (P < 0.21) and survival at 3 yr was identical for all BCA cases. Tumor grade, stage, and lymph node status did not significantly correlate with ploidy pattern. Thus, although DNA analysis does not seem to predict ultimate outcome in BCA, aneuploidy and high DNA index are associated with Barrett's esophagus with dysplasia and BCA and may be of significant value in the differentiation from variable reactive atypia in small biopsies. PMID- 8008740 TI - Necrotizing medullary lesions in patients with ANCA associated renal disease. AB - One hundred and five renal specimens from patients with antineutrophil cytoplasmic antibody and antiglomerular basement membrane antibody-associated diseases were reviewed for necrotizing lesions involving the renal medulla. Necrotizing medullary lesions were identified in eight of 56 cases in which medullary tissue was present. All eight were in patients with antineutrophil cytoplasmic antibody (ANCA) associated disease (seven, C-ANCA; one P-ANCA). Four types of medullary lesions were identified; necrotizing capillaritis (seven cases), necrotizing arteriolitis (two cases), pathergic granulomas (three cases) and papillary tip necrosis (one case). Both medullary arteriolitis and medullary peritubular capillaritis developed without corresponding cortical arteriolitis or cortical peritubular capillaritis. Although necrotizing glomerulonephritis was present in seven of eight patients, its activity did not parallel the severity of the medullary lesions. We conclude that several forms of necrotizing medullary vascular lesions may develop in ANCA-associated disease and that there is discordance between state of activity and types of vessel affected between cortical and medullary vascular compartments. PMID- 8008742 TI - Total parenteral nutrition: a histopathologic analysis of the liver changes in 20 children. AB - The histologic features of liver biopsies from 20 children treated with total parenteral nutrition (TPN) are presented. All the children received TPN for no less than 2 wk. Conditions that led clinicians to use this form of treatment included prematurity, sepsis, and gastrointestinal surgical procedures. Fourteen children had a history of prematurity; in nine the birth weight was between 640 and 1300 g. Gestational age and birth weight were not available in five and 11 children, respectively. Ten of the 20 children died. Our findings suggest that the morphologic features observed in the liver can be correlated with the duration of TPN. Thus, we propose a time table of hepatic histologic findings beginning with cholestasis and culminating in cirrhosis. PMID- 8008741 TI - Glutathione S-transferase expression in renal cell carcinoma: a new marker of differentiation. AB - Expression of two GST isoenzymes (alpha and pi) was assessed immunohistochemically in 46 cases of renal cell carcinoma (RCC) for which clinical follow-up was available. In the normal kidney GST alpha stained most intensely in the proximal convoluted tubules and GST pi in distal tubules/collecting ducts. All 46 tumors studied stained positively for GST alpha with most demonstrating strong cytoplasmic and nuclear reactivity. GST pi immunostaining was positive in 35/46 cases (76%). Five-year survival for patients with GST pi positive tumors was 88% versus 50% for those with GST pi negative tumors (P < 0.008). Loss of GST mRNA has been reported in RCC and it has been suggested that this may represent a dedifferentiation program in RCC. These data support this hypothesis and further indicate a potential value for GST pi as a prognostic indicator in RCC. PMID- 8008743 TI - DNA image cytometry of prostatic carcinoma: a comparison of needle core biopsy and subsequent prostatectomy specimens. AB - DNA ploidy has recently been identified as an objective prognostic factor in prostatic carcinoma. Although the diagnosis of prostatic carcinoma is increasingly being made with the use of needle core biopsies, the optimal method for the cytometric analysis of these specimens has yet to be determined. In addition, the degree to which the biopsy is representative of the subsequent prostatectomy specimen with respect to DNA heterogeneity has not been adequately addressed. In this study, image cytometric (ICM) DNA analysis was performed on tissue sections from 12 prostatic needle core biopsies and the results were compared with similar ICM analysis of the subsequent prostatectomy specimens. Multiple blocks (n = 48) of the prostatectomy specimens were utilized to prepare tissue sections and nuclear suspensions and each set of preparations were analyzed by ICM in a parallel comparison study. There was concordance of 0.80 in the classification of DNA diploid and aneuploid tumors by ICM analysis of tissue sections and nuclear suspensions from paraffin blocks. In all of the discordant cases, DNA aneuploid populations were identified by ICM analysis of tissue sections only. This is attributed to difficulties in obtaining a representative nuclear suspension from disaggregated paraffin-embedded prostatic tissue which often has a very desmoplastic stroma. ICM analysis of tissue sections seems to be an optimal method for DNA ploidy analysis of prostatic carcinoma and is well suited to small volume biopsy material. Determination of DNA ploidy status in prostatic biopsies was predictive of the subsequent prostatectomy specimens with a concordance of 0.92. PMID- 8008744 TI - Analysis of regional differences of p53 mutation in advanced gastric carcinoma: relation to heterogeneous differentiation and invasiveness. AB - In order to examine the correlation of p53 mutation with heterogeneous histological differentiation and invasiveness of gastric carcinoma, we analyzed 46 areas (three to six per case) that were different histologically and anatomically in 12 advanced gastric carcinomas, shown previously to be positive for p53 mutation, using immunohistochemical, polymerase chain reaction-single strand conformation polymorphism, and direct DNA sequencing analyses. DNA derived from different sites in nine cases had the same pattern of p53 mutation, even in cases manifesting heterogeneous histology within a single tumor. Site difference of the p53 mutation was found in three cases: two showed no mutation in superficial tumor areas but presence of mutation in deep-infiltrating areas. In contrast, one case contained a mutation in the superficial area but not in the deep-infiltrating area. These results suggest that in most cases, tumor cells forming a single advanced gastric carcinoma, even though they may present a heterogeneous histology and deep invasion, seem to be derived from the same cellular clone. PMID- 8008745 TI - Endobronchial lipomas: a clinicopathologic study of four cases. AB - Four cases of endobronchial lipomas are presented. The patients were men between 45 and 54 yr of age. Clinically, two of the patients presented with cough and one with shortness of breath. Two lesions were located in the left lower lobe, one in the right upper lobe, and one in the right lower lobe. Because of the clinical suspicion of malignancy, all patients underwent radical surgical procedures; lobectomy was performed in 3 patients, and pneumonectomy in one. Grossly, all the lesions were characterized by well-circumscribed, soft, yellow nodules that ranged in size from 1.2 to 3.0 cm in greatest diameter. Histologically, the tumors resembled lipomas in other locations, i.e., they were composed of mature adipose tissue devoid of atypia. In two cases, prominent spindle cell areas were also present similar to those of spindle cell lipoma. Identification of the lesion by endoscopic and radiologic means may help avoid unnecessary radical surgery. A review of the literature on these unusual lesions is presented along with a discussion of their differential diagnosis. PMID- 8008746 TI - ACTH-independent macronodular adrenocortical hyperplasia: immunohistochemical and in situ hybridization studies of steroidogenic enzymes. AB - ACTH independent bilateral macronodular adrenocortical hyperplasia (AIMAH) is associated with autonomous hypercortisolism. We report six cases of AIMAH, in which immunohistochemical studies on steroidogenic enzymes (P450scc, 3 beta HSD, P450c21, P450c17, P450c11) were performed on surgically resected adrenal glands. In situ hybridization studies of P450c17 were performed in two cases in order to localize the sites of steroidogenesis. Immunoreactivity to P450scc, P450c21, and P450c11 was observed in both clear and compact cortical cells, with compact cells displaying more intense staining, as reported in Cushing's adenoma and ACTH dependent bilateral adrenocortical hyperplasia. Immunoreactivity to P450c17 was observed predominantly in small compact cells, whereas that to 3 beta HSD occurred exclusively in clear cortical cells. In situ hybridization also demonstrated that P450c17 was localized in small compact cortical cells. This differential expression of 3 beta HSD and P450c17 in clear and compact cortical cells has been observed only in AIMAH among adrenocortical disorders. This ineffective corticosteroidogenesis may contribute to the relatively low production of cortisol. AIMAH should therefore be considered as a distinct subtype of primary adrenocortical Cushing's syndrome. PMID- 8008748 TI - Maude Abbott Lecture. Hematopathology: a crescendo of scholarly activity. AB - This lecture traces the evolution of hematopathology from the time of Thomas Hodgkin to the modern era of hybridoma antibodies, immunophenotyping, and molecular biology. It highlights the early concepts of Ludwig Aschoff and his school based on the observations of Metchnikoff, Ehrlich, and Maximow and the changes in concepts and terminology that have occurred in the ensuing 80 yr. The ongoing controversy on terminology and classifications of the malignant lymphomas from their first descriptions by Rudolf Virchow, Hans Kundrat, and Theodore Billroth is reviewed with reference to the development of the Working Formulation of Non-Hodgkin's Lymphomas for Clinical Usage and other classifications that are currently in vogue. Special attention is paid to the remarkable insight showed by Dorothy Reed in her morphologic descriptions of Hodgkin's disease, her thoughtful discussion on the nature of this disorder, and the conformation of her proposals inherent in the subsequent classification of Lukes and Butler. Acknowledgement is given to the remarkable discovery of Kohler and Milstein resulting in the advent of monoclonal antibodies that have revolutionized the field of hematopathology; to the many immunopathologists who have been responsible for the production of more than 1100 monoclonal antibodies comprising 78 clusters of differentiation; and to many of the leading molecular biologists who have (in the words of Berard) "helped to transform hematopathology from a difficult morphologic exercise into a functionally oriented biologic science." PMID- 8008747 TI - Prognosis of gastric carcinoma revealed by interactions between tumor cells and basement membrane. AB - The extra-cellular matrix (ECM) related antigens, type IV collagen, laminin, M(r) 68,000 laminin receptor (LR), M(r) 72,000 type IV collagenase (MMP-2), its inhibitor TIMP-2, and alpha 2-macroglobulin expression have been immunohistochemically investigated in 100 cases of human gastric carcinoma with a 5-yr follow up. Basement membranes were inversely related to tumoral differentiation. At the early intramucosal stage of both intestinal and diffuse histological types, TIMP-2 was expressed by the majority of tumor cells (60/63%), whereas MMP-2+ and LR+ cells were in the minority (24/19%, 23/0%, respectively). At the early submucosal stage, TIMP-2+ cells moderately decreased in both histological types (49/49%), whereas a consistently higher number of both MMP-2+ and LR+ cells were detected only in the diffuse carcinomas (72%). In the advanced stage, the expression of TIMP-2 further declined (22/24%), although the other two antigens increased or maintained high levels of expression. AMG+ cells never exceeded 10% in either histological type at any stage. In the liver metastases, both MMP-2+ and LR+ cells were more numerous than in the primary tumor (P < 0.002 and P < 0.01). Patients who died from their primary tumor had higher percentages of LR+, MMP-2+, and AMG+ cells and lower percentages of TIMP-2+ cells with respect to survivors. We believe evaluation of ECM-related antigens, and especially TIMP-2, may help determine a confident prognosis for gastric cancer. PMID- 8008749 TI - Methods in pathology. p53 expression in formalin-fixed, paraffin-embedded archival specimens of intrahepatic cholangiocarcinoma: retrieval of p53 antigenicity by microwave oven heating of tissue sections. AB - Immunohistochemical demonstration of p53 is thought to reflect mutations of the p53 gene. Although p53 expression or mutation has been investigated in a variety of carcinomas, it has not been examined in intrahepatic cholangiocarcinoma (CC). We investigated expression of p53 in formalin-fixed, paraffin-embedded archival specimens of 40 CCs (22 autopsy cases and 18 surgical cases) by immunohistochemistry using four antibodies (PAb1801, DO-7, BP53-12, CM1). We also attempted to enhance p53 expression by pretreatments of tissue sections by pepsin digestion as well as by microwave oven heating. Formalin-fixed, paraffin-embedded archival surgical specimens of 15 colon carcinomas were used as controls. In surgical cases, p53 expression was abolished by pepsin predigestion, although it was greatly enhanced by pretreatment of microwave oven heating in all immunostainings (PAb1801, DO-7, BP53-12, CM1). In surgical cases immunostained with microwave oven heating, DO-7, BP53-12, and CM1 showed frequent p53 expression (22% in CC; 60-67% in colon carcinoma), whereas PAb1801 showed low p53 expression (0% in CC; 13% in colon carcinoma). In contrast to the surgical cases, all 22 CCs of autopsy cases showed no p53 expression by any antibodies as well as by any pretreatments. These results shows that a pretreatment of tissue sections by microwave oven heating is a very good method for demonstrating p53 protein in formalin-fixed, paraffin-embedded archival materials and that DO-7, BP53-12, and CM1 are useful antibodies for detection of p53 in formalin-fixed, paraffin embedded archival materials. No expression of p53 in autopsy cases of CC suggests that p53 antigenicity is lost during autopsy procedure.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8008750 TI - Methods in pathology. An improved method for DNA diagnosis of leprosy using formaldehyde-fixed, paraffin-embedded skin biopsies. AB - To improve the sensitivity of the previously reported polymerase chain reaction (PCR) for the detection of Mycobacterium (M.) leprae in the formaldehyde-fixed, paraffin-embedded tissues, we adapted the PCR designed to amplify an internal 372 bp fragment of a M. leprae-specific repetitive sequence to 39 skin biopsies taken from patients with leprosy of the lepromatous type and tuberculoid type. Crude DNA samples were prepared from tissue sections that were deparaffinized and subjected to proteinase-K digestion without any further treatment for DNA purification. Overcoming a false-negative reaction by an elongation of the period for enzymatic digestion and an appropriate dilution of the samples, an amplification of the target sequence was obtained as a single band with all 39 skin biopsies tested. The fragments specifically amplified by the PCR were subjected to direct sequencing and were confirmed to be identical with an internal 372 bp of M. leprae-specific repetitive sequence. Although in nine of 24 nonleprosy control samples, a false-positive amplification was observed as from one to several bands, they were distinguishable from the specific one by the electrophoretic pattern. This PCR makes up for the classic histological methods used in the diagnosis of leprosy. PMID- 8008751 TI - Correspondence re: B. Wagner. "The 'cause of death' is dying." Editorial. Mod Pathol 6:237, 1993. PMID- 8008752 TI - Correspondence re: B. Wagner, "The 'cause of death' is dying." Editorial. Mod Pathol 6:237, 1993. PMID- 8008753 TI - Molecular evolution of the family Camelidae: a mitochondrial DNA study. AB - We report the first molecular evolutionary analysis of the family Camelidae by analysing the full DNA sequence of the mitochondrial cytochrome b gene. Estimates for the time of divergence of the Old World (Camelini) and New World (Lamini) tribes obtained from sequence data are in agreement with those derived from the fossil record. The DNA sequence data were also used to test current hypotheses concerning the ancestors of the domesticated llama and alpaca. The results show that hybridization has occurred in the ancestry of both domesticated camelids, obscuring the origin of the domestic species. PMID- 8008754 TI - Microsatellite DNA variation within and among European cattle breeds. AB - Microsatellite markers offer great potential for genetic comparisons within and between populations. We report the analysis of 12 microsatellite loci in six breeds of European cattle. This yielded a wide spectrum of variability with observed heterozygosities ranging from 0.00 to 0.91. Deviations from Hardy Weinberg equilibrium were noted for some locus-population combinations, particularly at a microsatellite located within the prolactin gene. Also, significant linkage disequilibrium was detected between two microsatellite loci located within the bovine major histocompatibility complex, and this association was maintained across breeds, providing evidence for marker stability during short-term evolution. The mode of mutation was investigated by comparing the observed data with that expected under the infinite alleles model of neutral mutation, and six of the microsatellite loci were found to deviate significantly, suggesting that a stepwise mutation model may be more appropriate. One indication of marker utility is that, when genetic distance estimates were computed, the resultant dendrogram showed concordance with known breed histories. PMID- 8008755 TI - The association between microfilaraemia and disease in lymphatic filariasis. AB - A standard tenet in the epidemiology of lymphatic filariasis is that patent infection is negatively related to chronic disease. We examine the empirical evidence for this relation by using published data from field studies carried out in a variety of bancroftian filariasis endemic areas. Meta-analysis of the individual study results for each disease category of hydrocele in males only, lymphoedema only, and both conditions combined (total chronic disease) indicate, contrary to expectation, no evidence for a negative association between infection and disease. Indeed, the trend of the empirical evidence is towards the opposite direction, with the majority of studies showing equal propensity of disease in microfilaraemics (mf+ves) and amicrofilaraemics (mf-ves), and more studies indicating a positive rather than a negative relation. There was also a trend for more positive studies for hydrocele compared to lymphoedema. Theoretical analysis suggests that between-study differences in blood sample volumes are unlikely to confound this finding. Analysis of between-study heterogeneity suggests that variations in the local incidence or prevalence of infection rather than unique geographical, including vector, differences might underlie the observed between study variability in the microfilaraemia-disease association. These results are discussed in terms of dynamic explanations for infection-disease relations in lymphatic filariasis. PMID- 8008756 TI - Prediction of forced ventilation in animal fur from a measured pressure distribution. AB - A model and computation scheme are given for predicting forced ventilation in the fur on an animal limb or torso, modelled here as a fur-covered cylinder with the hairs erect. The intra-fur flow is described by an anisotropic Darcy model, and pressure distribution measured previously for flow past a solid cylinder at Reynolds number 1.29 x 10(5) is used for the outer flow. Calculations from the model are presented for five mammalian species. PMID- 8008757 TI - A pessimistic estimate of the time required for an eye to evolve. AB - Theoretical considerations of eye design allow us to find routes along which the optical structures of eyes may have evolved. If selection constantly favours an increase in the amount of detectable spatial information, a light-sensitive patch will gradually turn into a focused lens eye through continuous small improvements of design. An upper limit for the number of generations required for the complete transformation can be calculated with a minimum of assumptions. Even with a consistently pessimistic approach the time required becomes amazingly short: only a few hundred thousand years. PMID- 8008758 TI - The influence of 17 beta-oestradiol on K+ currents in smooth muscle cells isolated from immature rat uterus. AB - Potassium currents in cells isolated from myometrium of immature (23-26 days after birth) rats were measured by whole-cell patch clamp to analyse the effects of gonadal steroids. Predominantly outward K+ currents with an early transient component were recorded in response to depolarizing pulses from a holding potential of -90 mV. The transient current, which was rarely present in adult myometrial cells, was inactivated by holding the membrane potential at -40 mV and attenuated by 1 mM 4-aminopyridine. Under these conditions a second sustained outward current was apparent. Administration of 17 beta-oestradiol to the immature rat before isolation of the myometrial cells reduced the probability of occurrence of the transient currents from 78.6% of cells (n = 33) to 29.8% (n = 14). Progesterone had only a slight effect. The kinetics of the transient currents were differently influenced by the two steroids. Cells isolated from animals previously given 17 beta-oestradiol showed transient outward currents with significantly shorter time constants of decay than those for control cells. Conversely, progesterone caused the time constants to be increased. We conclude that the gonadal steroids exert an influence on the expression of different populations of ionic channels in isolated cells of the immature rat uterus. These channels may regulate the excitability and contractility of the uterus in vivo. PMID- 8008760 TI - Malaria parasites undergo antigenic variation at high rates in vivo. AB - The rates of switching between expression of variable antigen types (VATS) have been investigated in vivo in a cloned line of Plasmodium chabaudi chabaudi. VAT specific hyperimmune sera combined with an immunogold-silver staining technique were used to detect VATS, and five estimates of VAT-specific switching rates were determined for three of them. VAT-specific switching rates were consistent for each VAT and differed between VATS in the range 1.3 x 10(-2) to 4.3 x 10(-4) switches per schizont per generation. This variation suggests that hierarchical expression of VATS in an infection may be determined by switch rates. A minimum estimate of the overall switching rate was determined by summation of the VAT specific rates in each of two experiments. In both cases the results showed that at least 1 in every 80 schizonts switched VAT expression every generation. This is the first report of antigenic switching rates for malaria parasites measured in vivo in the presence of minimal specific immune pressure, and is the first to show that VAT-specific switching rates vary between VATS. We conclude that switching is rapid and spontaneous, and is regulated, at least in part, by the VATS involved. PMID- 8008759 TI - Modelling the impact of mass vaccination against hepatitis B. I. Model formulation and parameter estimation. AB - A new model of the transmission dynamics of hepatitis B virus in countries with high transmission rates is presented. The model is age and sex stratified, and includes details of host demography. Details of hepatitis B natural history, such as the existence of infectious and non-infectious carriers, are included. The biological assumptions of the model are discussed in full and related to the model's equations. Hepatitis B epidemiological data is reviewed with special emphasis on the estimation of model parameter values from field data. A full set of model parameter values are derived. Possible uses of the model in the assessment of strategies of mass vaccination are discussed. PMID- 8008761 TI - On the carrying capacity for large ungulates of African savanna ecosystems. AB - The effect of pastoral management on the standing crop biomass of large ungulates, an index of carrying capacity, is analysed at a regional level by using data compiled from published sources covering east and south Africa. The effect of primary production is controlled for by using two environmental factors, rainfall and soil nutrient availability, and the effect of species richness of the ungulate community is evaluated. The results confirm the dominant effect of rainfall, and demonstrate that soil nutrient levels also strongly affect the biomass of large ungulate communities. For a given level of rainfall, on rich soils (high nutrient availability) the biomass of large ungulates is about 20 times as great as on poor soils with low nutrient availability. The model based on rainfall and soil nutrient classes accounts for 87% of the variance in large ungulate biomass. Pastoral and natural ecosystems do not differ significantly in large ungulate biomass; there is therefore currently no evidence that extensive pastoral management increases carrying capacity for large ungulates above the levels observed in natural communities. Species richness, a measure of biodiversity, had a significant but very small effect on the biomass rainfall relation in the complete data set. When analysed by pastoral management, the effect of this factor was significant for the set of natural ecosystems only. Pastoral management and species richness may therefore have compensatory effects. These results suggest that the carrying capacity is limited at the community, rather than the species, level. PMID- 8008762 TI - Brooding and the evolution of parthenogenesis: strategy models and evidence from aquatic invertebrates. AB - Developmental defects are expected to be common and severe in the early evolution of parthenogenesis, and they could help to explain the predominance of sexual forms of reproduction. It is difficult, however, to see how such defects might explain the ecological and phylogenetic correlates of sex. Here we suggest that internally fertilized animals that brood their young may be more susceptible to invasion by parthenogenetic mutants. The reason is that brooders could establish 'selective arenas' in which developmentally defective embryos are competitively displaced. Brooders could also selectively abort defective embryos, and replace them with minimal cost. Consistent with these ideas, we found a striking association between brooding and parthenogenesis in aquatic invertebrates. For example, in the Cnidaria and Mollusca, parthenogenesis is significantly more common in lineages that retain their young through the early stages of development. Hence brooding and ecological factors (such as escape from parasites) might combine to explain the initial spread, long-term persistence, and phylogenetic distribution of parthenogenetic reproduction. PMID- 8008763 TI - Time to move on from the donor card. PMID- 8008764 TI - The longer the delay, the greater the anxiety. Delay in treatment for breast cancer. AB - While there has been much publicity about the importance of observing for breast changes and seeking medical help quickly, there are considerable variations in the waiting times for diagnosis and treatment. A study was undertaken to explore the extent of such delays and the reasons for them. PMID- 8008765 TI - How effective is training for blood pressure measurement? AB - Monitoring blood pressure is a procedure most medical and nursing staff frequently perform, and forms the basis for many decisions about treatment. This study, however, highlights a disturbing lack of clarity among practitioners about how the procedure should be performed. PMID- 8008766 TI - At the front line of care. The importance of nutrition in wound management. AB - While the importance of nutrition in wound healing has been acknowledged, nutritional assessment is often overlooked. It is therefore vital that patients' nutritional status are assessed on an ongoing basis. PMID- 8008767 TI - A developing information base for purchasing decisions. A review of pressure relieving beds for at-risk patients. AB - Purchasers of pressure-relieving equipment have little clinical data on which to base purchasing decisions. A selection criteria which includes gathering all available product information and assessing the technical benefits prior to purchase can help fill this information gap. PMID- 8008768 TI - A crisis offering an opportunity for growth. Burnout in AIDS care. AB - The intense and demanding nature of Aids/HIV care makes burnout hard to avoid. This article describes how professionals suffering from burnout can access new sources of energy that offer the potential for growth and renewal. PMID- 8008769 TI - Diagnosis and treatment of phobia. AB - A phobia is an excessive fear or dread of a situation or object which is out of keeping with the danger it may actually present. Phobias can be classified into 'simple phobias', 'social phobias' and agoraphobia. A number of psychological theories have been put forward to account for both the onset and maintenance of a phobia. The case of a social phobia is presented together with a cognitive behavioural intervention package. PMID- 8008770 TI - How should we define the caring role? Broadening the parameters of the concept of care. AB - There are many different interpretations of the dynamics of the nurse/patient relationship and the contrasting needs and priorities nurses and patients attach to it. This article outlines varying interpretations of the concept of care, and suggests the concept can be broadened to reflect the physical, emotional, cognitive and intuitive aspects of the caring role. PMID- 8008771 TI - Diabetes and food--the positive approach. Dietary advice for people with diabetes. AB - Providing dietary advice is an important part of diabetes care. By forsaking the traditional prescriptive approach and focusing instead on the need for a healthy, balanced diet, greater compliance may be achieved. PMID- 8008773 TI - Recognition of a major role: district nurses and health education. AB - While health education has always been seen as a major component of the district nurse's role, recent studies show that district nurses spend less time on health education than other community nurses. How should district nurses reinforce their role as health educators? PMID- 8008772 TI - An epidemic of massive proportions: Smoking and the health of the nation. AB - The number of deaths from smoking-related illness is still unacceptably high. The government aims to reduce cigarette consumption by the year 2000, but this can only be achieved if the social, psychological and political factors that induce people to start smoking are addressed. PMID- 8008774 TI - Time out but not wasted. PMID- 8008775 TI - The way irrelevant dimensions are processed depends on what they overlap with: the case of Stroop- and Simon-like stimuli. AB - According to the dimensional-overlap model (Kornblum, 1992), irrelevant dimensions that overlap with a stimulus dimension (e.g., Stroop-type stimuli) are processed by a different stage than those that overlap with the response (e.g., Simon-type stimuli). We show that the effects of these two types of overlap are additive, thus supporting the model's hypothesis. We also show that the time course of facilitation and interference is different for these two types of overlap. PMID- 8008776 TI - Attention shifts produce spatial stimulus codes. AB - In the Simon task the spatial position of the stimulus, though task irrelevant, influences speed of response. We (Umilta & Nicoletti, 1992) proposed that the orienting of attention to the imperative stimulus produces a Stroop-like interference. This paper reports the results of three experiments that provide empirical support for two predictions of this hypothesis. One is that the stimulus spatial code is formed with relation to the position to which attention is directed. The other prediction is that the Simon effect is obtained on condition that attention can orient to the stimulus. PMID- 8008777 TI - The functional role of attention for spatial coding in the Simon effect. AB - Two experiments investigated relative spatial coding in the Simon effect. It was hypothesized that relative spatial coding is carried out with reference to the position of the focus of visual attention. The spatial code for an imperative stimulus presented exactly at the position of focal attention should be neutral on the horizontal plane, and therefore no Simon effect should be observed. However, when the imperative stimulus is presented to the left or to the right of the current position of focal attention, the spatial code should not be neutral, thus producing a Simon effect. In both experiments, focal attention was manipulated either by a peripherally presented onset precue (Experiment 1) or by a centrally presented symbolic precue (Experiment 2). Results showed that the Simon effect was substantially reduced in both experiments when a valid precue preceded the imperative stimulus just in time to conclude refocusing of attention to the position of the imperative stimulus before it was presented. However, conditions with neutral precues yielded a normally sized Simon effect. In both experiments, the Simon effect decreased as the SOA grew when the precue was valid. At least for the Simon effect, the results can be interpreted as evidence that relative spatial coding is functionally related to the position of the focus of attention. PMID- 8008778 TI - The Simon effect and visual motion. AB - S-R compatibility and Simon effects were studied for real visual motion. In Experiment 1, two small stimulus lights were constantly visible, 5 degrees to the left and right of fixation; after a random delay, one began to move at 2 degrees/s. In Experiment 2, a single stimulus light moving at 2 degrees/s suddenly appeared 5 degrees to the left or right of fixation, i.e., motion onset and stimulus onset coincided. In both experiments, subjects responded by a key press with their left or right index finger as soon as they detected motion. In Condition A responses were made to the position (left or right) from which the motion started, irrespective of its direction (position compatibility); in Condition B responses were made to the direction of motion (leftward or rightward) irrespective of whether motion started to the left or to the right of fixation (direction compatibility). The results show strong compatibility effects for both position and direction of motion in both experiments. A Simon effect, however, occurred only when position was task irrelevant in Experiment 1; no Simon effect was found in Experiment 2. The data only partly confirm previous results obtained with apparent motion. The selective lack of a Simon effect supports the integrated model of Umilta and Nicoletti (1992), which requires orienting of attention for the Simon effect to occur. It is specifically assumed that this attention-orienting is triggered only by the saccade program and does not extend to the pursuit program that is initiated by smooth stimulus motion. PMID- 8008779 TI - Hand-hemispace spatial compatibility, precueing, and stimulus-onset asynchrony. AB - The role of attention and the resolution of coding conflicts in hand-hemispace spatial-compatibility effects was examined in a precueing experiment in which visual and vibrotactile precues, with various stimulus-onset asynchronies (SOAs), were presented in blocked and random order. It was expected that precues at the shorter SOAs would fail to facilitate the shifting of attention, as they occur too close to the imperative stimulus to be informative. The task would therefore approximate one of choice reaction time (RT), resulting in a hand-hemispace spatial-compatibility effect. Conversely, the longer SOAs would provide the subject with sufficient time in which to shift attention fully, and would therefore result in a task more like that of simple reaction time (SRT). It was expected that the hand-hemispace spatial-compatibility effect would then be absent. As was expected, this effect was present at the shorter SOAs, and absent at the longer SOAs. In Experiments 2 and 3, provision of a visual precue further facilitated attentional deployment, as did blocking the presentation of various SOAs in Experiment 3. Vibrotactile and visual precues did not differ in their ability to direct attention, implying that these modalities orient attention and precue location in essentially similar ways. These findings are discussed within the context of the mechanisms though to underlie the time course of spatial compatibility and the dissipation of a fading trace of interfering spatial codes. PMID- 8008780 TI - Effects of irrelevant spatial S-R compatibility depend on stimulus complexity. AB - Choice-reaction time is known to depend on the spatial correspondence of stimulus and response, even if the stimulus location is irrelevant to the task (Simon effect). An experiment investigated whether this effect depends on stimulus complexity--i.e., on whether properties of the stimulus render stimulus discrimination easy or difficult. It was hypothesized that high demands on discrimination slow down the processing of stimulus identity in relation to location, so that the facilitating or conflicting location code has more time to decay, thus losing impact on response selection. In fact, the results revealed an effect or irrelevant spatial S-R correspondence with easy, but not with difficult, stimulus discrimination. This finding resolves an apparent contradiction between the results of several previous experiments on the Simon effect. PMID- 8008781 TI - Referential coding and attention-shifting accounts of the Simon effect. AB - Stoffer (1991) and Umilta and Nicoletti (1992) have proposed an attention shifting account of the Simon effect. However, Hommel (1993) has presented evidence suggesting that the effect can be explained in terms of referential coding, without invoking attentional shifts. Five experiments are reported here, whose primary purpose is to test implications of the referential-coding account. All of the experiments compared conditions in which a noise stimulus was presented in the position opposite the target stimulus with conditions in which it was not. Contrary to the referential-coding account, (a) the basic Simon effect was larger without a fixation point to serve as a referent than with one; (b) the noise stimulus increased the magnitude of the Simon effect when a fixation point was used, but not when there was no fixation point; and (c) the magnitude of the Simon effect obtained in the presence of a noise stimulus was reduced substantially when the noise and the target (and, if present, the fixation point) were in different colors. The results, although counter to predictions of the referential-coding account, can be accommodated by the attention-shifting account if it is assumed that a fixation point provides an anchor that minimizes attention shifts. PMID- 8008783 TI - Does stimulus correspondence account for the Simon effect? Comments on Hasbroucq and Guiard (1991) AB - In a recent paper analysing the Simon effect, Hasbroucq and Guiard (1991) concluded that stimulus congruence, a correspondence relationship between stimulus components, accounts for the Simon effect and explains its reversal in the Hedge and Marsh experiment (1975). We contend that their definition of stimulus congruence is applied inconsistently, which invalidates their conclusion. It is argued here that the effect of display-control arrangement correspondence (Simon, Sly, & Vilapakkam, 1981) is an alternative account that fits the presented data better. In a second experiment, Hasbroucq and Guiard (1991) claimed to have invalidated the suggestion that display-control arrangement correspondence could be considered to be an alternative account of the findings in their Experiment 1. However, we assert that the type of display control arrangement employed in their second experiment was so unpredictable that no effect of display-control arrangement correspondence could occur. PMID- 8008782 TI - Stimulus congruence and the Simon effect. AB - A standard experimental procedure was implemented with novel response requirements to assess the hypothesis that the Simon effect is attributable not to the irrelevant stimulus-response relationship, but to the congruence between stimulus attributes. The stimulus ensemble consisted of the words LEFT and RIGHT, one of which was presented on each trial to the left or right of a central fixation point. The distinctive feature of the task is that subjects were asked to respond, by laterally placed keys, whether or not the stimulus word was in accord (i. e., congruent) with its location on the display. Asking subjects to judge stimulus congruence directly enables the effect of congruence to be assessed, as well as independent estimates of the two irrelevant S-R relationships that apply in the task--that is, between the response location and (1) the stimulus location (the Simon effect) and (2) the stimulus word (the reverse Simon effect). Marked effects were obtained in all three cases. Stimulus congruence remains in contention as a factor in the explanation of the Simon effect, but the strong effects of irrelevant S-R factors suggest that a more comprehensive account of the Simon effect is needed. An explanation in terms of stimulus salience, based on an interactive activational model, is briefly discussed. PMID- 8008784 TI - SPR Award, 1993. For distinguished contributions to psychophysiology: John Stern. PMID- 8008785 TI - Effect of relaxation training on cardiac parasympathetic tone. AB - To examine the hypothesis that the relaxation response is associated with an increase in cardiac parasympathetic tone, the frequency components of heart rate variability during relaxation training were investigated in 16 college students. Electrocardiograms and pneumograms were recorded during a 5-min baseline period followed by three successive 5-min sessions of the autogenic training (relaxation) or by the same periods of quiet rest (control), while subjects breathed synchronously with a visual pacemaker (0.25 Hz). Although neither the magnitude nor the frequency of respiration showed a significant difference between relaxation and control, the amplitude of the high-frequency component of heart rate variability increased only during relaxation (p = .008). There was no significant difference in the ratio of the low-frequency (0.04-0.15 Hz) to the high-frequency amplitudes. The increased high-frequency amplitude without changes in the respiratory parameters indicates enhanced cardiac parasympathetic tone. Thus, our results support the initial hypothesis of this study. Enhanced cardiac parasympathetic tone may explain an important mechanism underlying the beneficial effect of the relaxation response. PMID- 8008786 TI - The relationship between cardiovascular reactivity and heartbeat detection. AB - This experiment tested the hypothesis that inotropic cardiovascular reactivity to stress is related to performance on heartbeat discrimination tasks. The experiment also compared the efficacy of a specific modification of two popular heartbeat discrimination paradigms, Whitehead's and Katkin's. Subjects were 48 male undergraduates who performed both discrimination tasks and then were subjected to mental arithmetic stress. Results indicated that high cardiovascular reactors were better detectors than low reactors. Results also indicated that subjects performed better on the modified Whitehead task than on the modified Katkin task. PMID- 8008787 TI - Baseline respiratory sinus arrhythmia and heart rate responses during sustained visual attention in preterm infants from 3 to 6 months of age. AB - Three groups of preterm infants were studied longitudinally at 14, 20, and 26 weeks of age (corrected for gestational age). The groups included infants with no perinatal medical complications, those with mild respiratory problems requiring ventilatory assistance, and those with respiratory distress syndrome. Baseline heart rate and respiratory sinus arrhythmia (RSA) were recorded for 5 min, and heart rate was also recorded while the infants engaged in sustained visual attention to stimuli presented on video monitors. The heart rate response during stimulus orienting and sustained attention was smaller in those infants with respiratory distress syndrome than in the other preterm infants and in comparison with the response seen in full-term infants in previous research. Magnitude of RSA was positively correlated with the attention responses irrespective of the preterm group assignment. There was greater stability in baseline heart rate and RSA for the preterm infants than has been found with full-term infants. These data suggest that the cardiorespiratory functioning of the preterm infant indexes a stable individual difference characteristic that is correlated with heart responses during sustained attention, and heart rate attention systems may be damaged in the high-risk preterm infant. PMID- 8008789 TI - Alcohol and the physiological detection of deception: arousal and memory influences. AB - Eighty male volunteers participated in an analogue study of the effects of alcohol intoxication at the time of a crime on the physiological detection of deception using control question and guilty knowledge techniques. Sixty-four of the subjects committed a mock crime and half of these were intoxicated during the crime. Sixteen subjects committed no crime and served as innocent controls. We found that intoxication at the time of the crime had no significant effect on polygraph test outcomes, although it did affect anticipatory arousal before the crime and subsequent memory for crime details. Manipulations designed to influence memory for crime details and arousal during the crime had differential effects for the two polygraph tests. On the guilty knowledge test, primed subjects who rehearsed specific details following the crime were more detectable than unprimed subjects. On the control question test, primed subjects were also more detectable, but only when arousal during the crime was high. PMID- 8008788 TI - ERP and behavioral changes during the wake/sleep transition. AB - Event-related potentials (ERPs) following infrequent and frequent stimuli were studied as subjects moved from wakefulness to sleep. Subjects were instructed to respond to the infrequent "target" stimuli (attend condition) or to ignore the stimuli (ignore condition). Parietal P300, prominent following target ERPs in wakefulness under the attend condition, disappeared in association with reduced behavioral responsiveness and emergence of a central negativity (N350). The N350 and preceding and following positivities (P220 and P450) became the dominant feature of both target and nontarget ERPs under both attend and ignore conditions. The P220-N350-P450 complex was larger and peak latencies were shorter under the attend condition. Peak amplitudes tended to be larger following targets, especially under the attend condition. The findings suggest that, although the processes underlying P300 are less likely to be engaged, processing of stimulus deviance and task relevance continues in sleepiness and sleep, and is reflected by variance in N350 and related activity. PMID- 8008790 TI - The effects of an acute psychological stressor on cardiovascular, endocrine, and cellular immune response: a prospective study of individuals high and low in heart rate reactivity. AB - High and low reactors were preselected on the basis of their heart rate reactivity to a speech stressor in a prescreening session. In the main study, subjects were exposed to a mental arithmetic plus noise stressor. Cardiovascular activity was recorded during baseline and stressor, and blood was drawn prior to and following the stressor for endocrine and immune assays. Results revealed that the stressor decreased the blastogenic response to concanavalin A and increased natural killer cell numbers and cytotoxicity, absolute numbers of CD8+ T lymphocytes, norepinephrine and epinephrine levels, heart rate, and blood pressure responses. In addition, cortisol and natural killer cell cytotoxicity responses to the stressor differentiated individuals high versus low in heart rate reactivity. These results suggest that the interactions among the autonomic nervous system, endocrine system, and immune system are not only amenable to psychophysiological analysis but that such analyses may play an important role in illuminating underlying mechanisms. PMID- 8008791 TI - Reduced attention-related negative potentials in schizophrenic adults. AB - Event-related potentials were recorded from outpatient adult schizophrenics receiving maintenance doses of neuroleptics and from normal control subjects during performance of a reaction time task and a complex visual discrimination task, the Span of Apprehension. Difference potentials were computed to isolate endogenous activity associated with the processing demands of the Span task. Schizophrenics produce significantly less early endogenous negative activity than do normal subjects. This processing-related negativity reflects pattern matching activity to an attentional trace during the serial scan of the visual icon. We previously reported an identical reduction in processing-related negativity in childhood-onset schizophrenia, suggesting that this deficit is age independent. Both frontal contingent negative variation and an early frontal P3 were larger in the schizophrenics than in normal subjects, suggesting an inappropriate mobilization of nonspecific attentional resources. A later posterior P3 was significantly smaller in schizophrenics than in normal subjects. PMID- 8008792 TI - Stimulus dimensions of the cold pressor test and the associated patterns of cardiovascular response. AB - Hemodynamics of the cold pressor response in relation to its pain and nonpain stimulus components were investigated in normotensive college men using the foot and forehead cold pressor tasks. Mechanisms of pain- and non-pain-related increases in blood pressure were analyzed as residual effects of concurrent changes in total peripheral resistance and cardiac output. The identified partial relationships suggested that the response pattern associated with pain included positive change both in cardiac output and in total peripheral resistance, whereas the nonpain-related response was limited to an increase in total peripheral resistance. Analyses of individual differences in cardiovascular responses to pain further indicated that pain-related increments in blood pressure were mediated by a steeper rise in total peripheral resistance, an increase in heart rate, and an apparent increase in preload. At baseline, high reactors to pain manifested relatively elevated total peripheral resistance, diminished cardiac output, and an indication of a reduced inotropic state, suggesting that altered basal homeostasis may discriminate normotensive individuals displaying heightened cardiovascular reactivity to aversive cold stimulation. PMID- 8008794 TI - Effects of data limitations on heartbeat detection in the method of constant stimuli. AB - In the method of constant stimuli applied to measuring heartbeat detection, subjects judge the simultaneity of heartbeats and exteroceptive comparison stimuli presented at various intervals after the R-wave (0, 100, 200, 300, 400, and 500 ms). Using versions of this procedure, investigators have found that between 20% (Yates, Jones, Marie, & Hogben, 1985) and 54% (Brener, Liu, & Ring, 1993) of subjects can detect heartbeat sensations. Whereas Yates et al. used a single comparison stimulus on each trial and Brener et al. used 10, the present study examined whether this disparity in heartbeat detection performance could be attributed to the number of comparison stimuli presented on each trial. In each of 360 trials, 30 subjects judged the simultaneity of heartbeat sensations and tones following 1, 5, or 10 comparison stimulus presentations. Significantly fewer subjects met the criterion for heartbeat detection with 1 tone presentation (13%) than with either 5 (43%) or 10 (47%) tone presentations. It is concluded that a single stimulus presentation imposes data limitations that result in underestimation of the accuracy of heartbeat detection. The presentation of at least 5 stimuli in each trial alleviates this limitation. PMID- 8008793 TI - Electrophysiological correlates of feature analysis during visual search. AB - Event-related brain potentials (ERPs) were recorded from normal young adults during visual search tasks in which the stimulus arrays contained either eight identical items (homogeneous arrays) or seven identical items and one deviant item (pop-out arrays). Four experiments were conducted in which different classes of stimulus arrays were designated targets and the remaining stimulus arrays were designated nontargets. In Experiments 1 and 2, both target and nontarget pop-out stimuli elicited an enhanced anterior N2 wave and a contralaterally larger posterior P1 wave, but Experiments 3 and 4 demonstrated that these components do not reflect fully automatic pop-out detection processes. In all four experiments, target pop-outs elicited enlarged anterior P2, posterior N2, occipital P3, and parietal P3 waves. The target-elicited posterior N2 wave contained a contralateral subcomponent (N2pc) that exhibited a focus over occipital cortex in maps of current source density. The overall pattern of results was consistent with guided search models in which preattentive stimulus information is used to guide attention to task-relevant stimuli. PMID- 8008795 TI - Needle electromyographic evaluation of trigger point response to a psychological stressor. AB - Fourteen subjects were evaluated by needle electromyography in a trapezius myofascial trigger point and simultaneously in adjacent nontender trapezius muscle fibers during a control condition (forward counting), a stressful condition (mental arithmetic), and resting baselines. Based on recent data implicating autonomic innervation in muscle function, we hypothesized that the trigger point would be more responsive than the adjacent muscle to psychological stress. The results showed increased trigger point electromyographic activity during stress, whereas the adjacent muscle remained electrically silent. These results suggest a mechanism by which emotional factors influence muscle pain. This may have significant implications for the psychophysiology of pain associated with trigger points. PMID- 8008796 TI - Mental disorders in chronically ill children: case identification and parent child discrepancy. AB - Children, like adults and parents, depend on primary care physicians to identify, treat, or refer those with mental disorders. Mental health concerns are also germane to the growing number of chronically ill children in pediatric care. This paper focuses on: 1) the level of agreement between children and parents about the presence of a mental disorder and the impact of informant on case identification; and 2) the extent to which pediatricians agree with reports by chronically ill children and/or their parents regarding such problems. The study sample includes 112 children, ages 9 to 18, with cancer, cystic fibrosis, inflammatory bowel disease, and insulin-dependent diabetes and a control group of 35 healthy subjects. Subject and a parent were interviewed separately using a highly standardized, structured interview that generates DSM-III-R diagnoses by computer algorithms. Pediatricians completed a questionnaire asking about the presence of any mental disorders. Agreement between parent and child was poor for both groups. In the medically ill group, more cases were identified by the parent interview than by child interview alone for all types of disorders. In contrast, children in the comparison group more often reported symptoms sufficient for a diagnosis than did their parents. The difference in prevalence between the two groups was significant only for the parent-identified cases, and physicians were more likely to recognize child-identified disorders. The choice of informant(s) has clear implications for case identification and case recognition in both clinical care and research in pediatric settings. PMID- 8008797 TI - Depressive symptoms among general medical patients: prevalence and one-year outcome. AB - Using prospective data from the National Institute of Mental Health (NIMH) Epidemiologic Catchment Area surveys, we examined the relationship of depressive symptoms among patients seen by general medical practitioners, with the subsequent development of major depressive disorder. The goals of the analysis were to determine 1) the 1-year psychiatric status of these individuals, and 2) to evaluate factors associated with the risk of major depressive disorder (MDD) or dysthymia. Between 1980 and 1984, collaborators of the NIMH Epidemiologic Catchment Area program recruited 18,571 adult participants after probability sampling of census tracts and households in five metropolitan areas. To assess the occurrence of psychiatric conditions over time, staff administered the Diagnostic Interview Schedule soon after sampling and again at follow-up 1 year later. For this analysis, the study sample was limited to respondents who reported seeing a general medical physician in the previous 6 months and who were free of current depressive disorder at the baseline interview. Overall, 41% of the general medical patients reported experiencing at least one depressive symptom in the past 6 months. Between 3 and 5% of the individuals with depressive symptoms developed MDD or dysthymia at the follow-up interview. Although individuals with depressed mood had a slightly higher estimated relative risk compared with individuals with vegetative, or nonvegetative (cognitive) depressive symptoms, no single classification of symptoms was appreciably more likely to signal MDD or dysthymia 1 year later. However, the risk of depression increased with the number of depressive symptoms reported.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8008798 TI - Somatization symptoms in chronic low back pain patients. AB - Chronic low back pain (CLBP) patients often are described as "somatizers", who report multiple somatic complaints beyond back pain itself, but the nature and clinical significance of this observation is poorly understood. To clarify the characteristics, correlates and severity of somatization in CLBP, we rigorously assessed somatization symptoms in a sample of patients not selected for psychiatric or pain clinic referral. Male CLBP patients (N = 97), attending a primary care orthopaedic clinic, and matched healthy controls (N = 49), were assessed using the Diagnostic Interview Schedule III-A (DIS), Beck Depression Inventory (BDI), Hamilton Rating Scale for Depression (HRSD), McGill Pain Questionnaire (MPQ), Sickness Impact Profile (SIP), and the Pain and Impairment Relationship Scale (PAIRS). Although none of the subjects met strict DSM-III criteria for a lifetime diagnosis of Somatization Disorder, 25.8% of CLBP patients reported a lifetime history of 12 or more somatic symptoms, as compared to only 4.1% of controls. In the less symptomatic ranges, patients still generally reported more symptoms than controls, with 51.5% of patients vs. 8.2% of controls reporting 7-11 symptoms, and 22.7% vs. 87.8% of controls reporting 0 6 symptoms (p < .001). Major depression and alcohol dependence were significantly associated with increased severity of somatization (p < .05). Lower mood and increased impairment, but not pain intensity, were related to greater number of somatic complaints. Symptoms of somatization are prevalent, but not universal, in CLBP and the pattern of these symptoms is reminiscent of the "spectrum of severity" reported in other medical populations. Recognizing this spectrum of somatization may lead to better patient-treatment matching and improved clinical outcomes. PMID- 8008799 TI - Patient presentation, interview content, and the detection of depression by primary care physicians. AB - This study was undertaken in order to better understand the detection of depression by primary care physicians. Specifically, we investigated the relationship between information gathered during the course of the medical interview and the subsequent diagnosis of depression. Forty-seven community-based primary care physicians, unaware of the mental health focus of this research, were videotaped in the office setting, as they interviewed two "typical" standardized patients who met DSM-III-R criteria for major depression. One patient presented with headaches and the other presented with palpitations and chest pain. After each interview, physicians were provided with physical findings and results of any diagnostic procedures they ordered, then asked to construct and explicate their differential diagnoses. The two patients were correctly diagnosed as depressed by 53 and 45% of the physicians. Although detection was related to greater amounts of information gathered, inquiry about the DSM-III-R criteria symptoms was generally low, and in no case was sufficient information acquired to make a formal DSM-III-R diagnosis of depression. However, a subset of the DSM-III-R symptoms (those related to disturbances of appetite, sleep, and other neurovegetative functions) were among the reasons cited for inclusion of depression in the differential, as were psychosocial stressors and the patient's appearance. These findings suggest that detection of depression is low by primary care physicians. PMID- 8008801 TI - Behavioral and biomedical research: a partnership for better health. PMID- 8008800 TI - Intervention for minor depression in primary care patients. AB - This study examines the effectiveness of an intervention for minor depression in primary care patients. One hundred fifty public care medical patients were randomly assigned to either an 8-week cognitive-behavioral course intended to help them use pleasant activities, constructive thinking, and interpersonal relationships to improve mood or a control condition. Assessments were completed at postintervention, 6 months, and 1 year. The results support the effectiveness of the intervention. Persons with minor depression assigned to the intervention experienced reductions in depressive symptomatology, which persisted through the 1-year follow-up. In addition, the intervention lowered the somatic symptomatology that was associated with minor depression. Finally, those with minor depression who received the intervention missed fewer appointments with their primary care provider during the following year than did those with minor depression who received no intervention. The results from this preliminary evaluation suggest that interventions addressing minor depression in medical patients are feasible and are effective in reducing both depressive symptomatology and associated problems. PMID- 8008802 TI - Alexithymia ratings in bulimia nervosa: clinical correlates. AB - Previous reports indicate that some patients with eating disorders have alexithymic characteristics, including affect deficit states and paucity of imagination. This study evaluated whether nonhospitalized patients with bulimia nervosa had elevated ratings of alexithymia in comparison to age-matched controls, and whether severity of bulimic symptoms was correlated with elevations in alexithymia ratings. Because alexithymia may be secondary to concurrent depression, this study was limited to patients with bulimia nervosa who were free of major depression. The authors compared alexithymia ratings for nonhospitalized normal weight women meeting DSM-III-R criteria for bulimia nervosa (N = 20) to healthy female volunteers (N = 20), utilizing the Toronto Alexithymia Scale (TAS) as the primary assessment instrument. Subjects also completed standardized rating scales for bulimic symptoms, depression, and anxiety. Alexithymia rating scale scores were significantly higher for patients with bulimia nervosa than for controls. In comparison to controls, patients had significant elevations on TAS factors reflecting affect deficit states, but normal scores for factors reflecting imagination and abstract thinking. Frequency of binge eating or purging behaviors was not correlated with alexithymia ratings. These data indicate that some patients with bulimia nervosa have alexithymic characteristics. Affect dysregulation was more prominent than limitation in fantasy or metaphorical thought. Additional studies are needed to assess whether presence of alexithymic characteristics may be predictive of response to treatment in patients with bulimia nervosa. PMID- 8008803 TI - Psychiatric problems in primary care: what are the problems, how will we recognize them, and how can we treat them? PMID- 8008804 TI - Methodologic issues in randomized trials of liaison psychiatry in primary care. AB - Most anxiety, depressive, and substance abuse disorders are treated exclusively in the primary care health system. However, recognition and treatment of these disorders in primary care is deficient. Psychopharmacologic and psychotherapeutic interventions have been developed and proven effective in randomized trials in specialty care. However, the results of successful trials of mental health interventions in specialty settings may not generalize to primary care settings because of epidemiologic differences in patients, differences in skills of providers, as well as differences in the very structure of care. The importance of the development of innovative randomized trials to improve recognition and treatment of mental illness in primary care is emphasized, as well as the methodologic problems inherent in carrying out these trials. PMID- 8008805 TI - The role of nursing in mental health reform. PMID- 8008807 TI - Montana's Blue Cross/Blue Shield--true blue? PMID- 8008806 TI - Bridging the medicine communication gap: the nursing connection. PMID- 8008809 TI - IV site rotation--48 vs. 72 hour intervals. PMID- 8008808 TI - The Briles report on women in health care. Changing conflict to collaboration in a toxic workplace. PMID- 8008810 TI - When "I'm a businessman" says shame. PMID- 8008811 TI - But the horse has left the stable. PMID- 8008812 TI - The preventive resin (composite resin/sealant) restoration: nine-year results. AB - This study was performed to examine the 9-year success of the composite resin/sealant restoration, which uses "sealing for prevention" of fissure caries rather than "cavity extension for prevention." Three hundred thirty-two Class I restorations were placed in the occlusal surfaces of 240 permanent molar teeth in 114 children aged 6 to 14. Cavity preparations were made in occlusal surfaces, and caries was removed with no attempt to create any additional retention or remove undermined enamel. Exposed dentin was covered with Dycal and the cavity was restored with Radiopaque Adaptic, which was then covered with Delton fissure sealant. Incipient lesions confined to the enamel were restored only with Delton. After 9 years, 79 restorations in 28 subjects were examined for sealant retention, marginal staining, and the presence of dental caries. Forty-three restorations (54%) had completely retained sealants, 20 (25%) had sustained partial loss, and 16 (20%) of the restorations had lost all sealant. Dental caries occurred in 19 (25%) of the restorations that had sealant loss. An additional 16 teeth had proximal caries unrelated to the occlusal restoration. These findings demonstrated that the composite resin/sealant (preventive resin) restoration produced excellent long-term results. PMID- 8008813 TI - Esthetic treatment of severe tetracycline staining with orthodontics and veneers: a case report. AB - This case history describes and illustrates the excellent esthetic results now clinically possible when fixed appliance orthodontic therapy is combined with porcelain veneers to treat severe tetracycline staining and crowding. Because the patient also presented with a bimaxillary protrusion and a displaced maxillary midline, the treatment options also illustrate the dilemma between ideal, but prolonged, treatment options and quicker, but compromised, alternatives. The excellent final result accepted the initial protrusion but corrected the midline. A long-span bonded multistrand wire functioned as semipermanent retention. PMID- 8008814 TI - Crown lengthening and restorative treatment in mutilated molars. AB - Crown lengthening has been advocated as a treatment modality to restore teeth with a clinical crown reduced subsequent to different kinds of trauma. Multirooted teeth, however, present certain anatomic features, such as the furcation area and corresponding interradicular bone, the retromolar area, and the external oblique ridge, that may limit the possibility for soft tissue and bone reduction and minimize the effectiveness of crown-lengthening procedures. This article describes surgical modifications to overcome the anatomic difficulties that multirooted teeth present when crown lengthening is required. Furthermore, root resection is discussed as an alternative to conventional surgery when the latter is not possible. PMID- 8008815 TI - Use of roots to establish favorable removable partial denture design: case reports. AB - Judicious retention of roots can alter the position of the anterior fulcrum line and so simplify removable partial denture design. Complicated tooth-tissue supported designs are thus transformed into much simpler tooth-supported removable partial overdentures. PMID- 8008816 TI - Lingualized occlusion in implant dentistry. AB - Occlusal requirements for implant prosthodontics, as well as the advantages and disadvantages of two occlusal schemes are discussed. Based on the requirements of fixed reconstruction, the concept of lingualized occlusion with anterior guidance is presented as an ideal occlusal scheme for many implant cases. It embodies the established requirements for fixed implant prosthesis, eases fabrication, and simplifies intraoral adjustment procedures. PMID- 8008817 TI - Permeability of protective gloves used in dental practice. AB - Two brands of latex rubber gloves and one brand of polyvinyl chloride glove were examined for their permeability. New and used gloves were included. All of the gloves were examined visually and then subjected to an air leakage test, an electrical test, and a microbiologic test. Permeability was evaluated independently by two researchers in a blind manner. Statistical analysis showed that there were no significant differences among the three brands of gloves or with respect to the usage periods, according to visual inspection and the air leakage test. Conversely, there were significant differences among each of the three brands of gloves and with respect to usage periods, according to the electrical and microbiologic tests. PMID- 8008818 TI - Mesio-occlusodistal amalgam restorations: quantitative in vivo data up to 4 years. A data base for the development of amalgam substitutes. AB - Wear and marginal quality of 14 mesio-occlusodistal amalgam restorations (Dispersalloy) were quantitatively analyzed in this in vivo study. Wear rates, measured as maximum vertical loss of substance in the occlusal contact area, were 41, 50, 57, 79, 82, 123, 165, and 215 microns after 1, 2, 3, 6, 9, 24, 36, and 48 months, respectively. In the contact-free occlusal area an expansion of 2 to 9 microns was recorded. The micromorphology of the tooth-amalgam interface significantly changed within the first 9 months after restoration placement. The percentages of marginal opening increased from 91% to 100%, marginal restoration fracture from 49% to 89% and underfilled margin from 50% to 78%. Amalgam restorations have clinically proved successful despite their poor marginal adaptation and their inferior wear resistance compared to enamel. Thus, the wear resistance of amalgam substitutes, preferably metal-free, tooth-colored restorative materials, would not necessarily have to exceed that of amalgam to replace it. The wear data generated may serve as guiding figures in the development of amalgam substitutes. PMID- 8008819 TI - The conservative management of a discolored pulpless premolar: a case report. AB - Endodontically treated premolars may discolor with time, impairing the esthetic appearance. Frequently combined with large defects, they are subject to an increased risk of fracture. The restoration of such teeth with a cast post and core and a separate porcelain-fused-to-metal crown results in additional loss of intact tooth structure. A case is presented in which the cavity of a discolored, pulpless maxillary premolar was restored, without further loss of tooth substance, with an adhesively luted porcelain inlay after intracoronal bleaching, a technique traditionally used to lighten discolored, pulpless anterior teeth. PMID- 8008820 TI - The treatment of palatal erosive wear by using oxidized gold veneers: a case report. AB - Eight maxillary anterior teeth with severe palatal erosion in an anorexic patient were restored with oxidized gold veneers and without tooth preparation. Because of the extensive exposure of dentin, a cement based on 4-methacryloxyethyl trimellitate anhydride was used as the luting agent. PMID- 8008821 TI - Wear of CAD/CAM ceramic inlays: restorations, opposing cusps, and luting cements. AB - Six standard mesio-occlusodistal restorations in extracted mandibular human molars and six opposing palatal cusps from maxillary human first molars were prepared per group. The occlusal contact areas of the restorations and of the opposing enamel cusps were digitized with a three-dimensional scanner. The specimens were exposed to a clinically correlated long-term in vitro wear test. Dicor MGC, Cerec Vita Mk I porcelain, Cerec Vita Mk II V7R porcelain, and Cerec Mk II Vita V7K porcelain were tested. The mean wear of these ceramic materials at the end of the long-term test ranged from 24.3 +/- 10.3 microns (Cerec Vita Mk II V7R) to 88.0 +/- 37.3 microns (Dicor MGC). The mean wear of the opposing human enamel cusps ranged from 93.5 +/- 30.8 microns (Cerec Vita Mk II V7R) to 224.3 +/ 117.4 microns (Cerec Vita Mk I). All ceramic materials except Dicor MGC wore less than did previously measured standards, such as natural human enamel and amalgam. However, because the wear of opposing enamel cusps was high with Dicor MGC and with Cerec Vita Mk I the total wear of these two materials--the sum of the restoration's and the opposing tooth's wear--was higher than that of the standards. Only the new fine porcelain Cerec Vita Mk II V7R showed a total wear comparable to that of enamel, because of its moderate abrasivity against opposing enamel. The wear of the two luting composite resins was measured at the end of the test. Both luting composite resins wore more than did the ceramic inlays and surrounding enamel, leaving a shallow ditch around the restorations. PMID- 8008822 TI - Comparison of patient-perceived postcementation sensitivity with glass-ionomer and zinc phosphate cements. AB - Numerous investigators have reported patients' postcementation sensitivity with glass-ionomer luting agents. This information has been predominantly anecdotal and unsupported by data. This paper reports on the actual perceptions of patients who had restorations cemented with both glass-ionomer and zinc phosphate luting agents. Forty-five patients were randomly selected and received two cast restorations, one cemented with glass-ionomer cement and the other with zinc phosphate cement, also by random assignment. After 1 week, patients returned to complete a self-administered evaluation of perceived sensitivity. Neither luting agent resulted in greater sensitivity when used according to its manufacturer's instructions. PMID- 8008823 TI - A new method to test the cohesive strength of dentin. AB - The cohesive plateau theory states that the strength at a bonded interface should equal the strength, cohesively, of the substrate with which it is bonded. A new method was developed to test cohesive strength of dentin so as to offer an opportunity to compare the data against shear bond strength values of commercially available dentinal bonding agents using the same test assembly. The method applied a shear force to a standard circular column of dentin continuous with the tooth from which it was cut with a tubular diamond drill. The mean cohesive strength of dentin in the shear mode, based on 30 specimens, was 36.18 +/- 6.81 MPa. PMID- 8008824 TI - cisDDP treatment and development of the rat cerebellum. PMID- 8008825 TI - The subretrofacial vasomotor nucleus: anatomical, chemical and pharmacological properties and role in cardiovascular regulation. PMID- 8008826 TI - Problem solving in artificial neural networks. PMID- 8008827 TI - Genetic dissection of signal transduction mediated by the sevenless receptor tyrosine kinase in Drosophila. AB - The specification of the R7 photoreceptor cell fate in the developing eye of Drosophila depends on the local activation of the sevenless (sev) receptor tyrosine kinase by boss, a protein expressed on the membrane of the neighboring R8 cell. Constitutive activation of the sev receptor results in a dosage dependent increase in the number of R7 cells per ommatidium. Genetic screens have been used to identify mutations that alter the efficiency of signal transduction. Subsequent molecular characterization of the corresponding genes has led to the identification of a number of proteins involved in transducing the signal from the receptor to the nucleus. In contrast to the receptor and its ligand, these components are shared between different signal transduction pathways not only in Drosophila but are also homologous to components involved in signal transduction in other organisms. PMID- 8008828 TI - Position-reading and the emergence of sense organ precursors in Drosophila. AB - Genetic analysis of development in Drosophila melanogaster has advanced our understanding of "position reading", where the expression of particular genes informs a cell of its position in the developing animal. The first step in localization of fly sense organs is the local expression of a gene conferring neural competence on epidermal cells. The four genes of the achaete-scute (AS-C) complex play crucial roles in the localization of sense organs. The resolution of local expression of AS-C genes along one dimension is about 10%; accuracy is improved by the balancing local expression of AS-C antagonist genes such as extramacrochaete. Position reading seems to depend primarily on such patterns of gene expression, and not upon the compartmental identity of the cells. No evidence has been found for differing roles of the four AS-C genes in the generation of sense organ progenitor cells or in the specification of neuronal properties of innervating neurons. The formation of each sense organ may be a unique case where the different proneural and neurogenic gene products have varying importance, and fortuitous local effects acting on this complex combination of factors have come to be important. The fly may be evolving from a flexible regular pattern to an inflexible irregular pattern strongly dependent on local factors, turning the fly into a crystallized system. (Written by R. Wayne Davies.). PMID- 8008829 TI - Reverse genetics of Drosophila brain structure and function. AB - A set of molecular genetic technologies are described, which will have far reaching consequences for the study of brain structure, function and development in Drosophila melanogaster. Site selected mutagenesis (a PCR-based screen for P element insertion events) allows insertion mutants to be isolated for any cloned gene, and is being used in this laboratory to ask questions about the rolls of particular cellular components in learning and memory. Transposants have been isolated in genes encoding a regulatory (RI) and a catalytic (DCO) subunit of cAMP-dependent protein kinase, and in a gene encoding a Gi-like alpha subunit. The alternative use of I factors is described. The PKA RI homozygous mutants display a significant decrement in initial learning ability. Enhancer-trap strategies, for which the GAL-4 P-element system is particularly convenient, allow the identification of genes expressed in the developing fly brain. Strategies for the efficient detection of such events are described. PMID- 8008830 TI - Exploring the mammalian neuromuscular system by analysis of mutations: spinal muscular atrophy and myotonia. AB - Any biological structure can be studied using mutations that interfere either with its emergence or its function. We investigate spontaneous and induced mutations in the mouse that affect neuromuscular development and function. The wobbler mouse (phenotype WR, genotype wr/wr) suffers from muscular atrophy because of the degeneration of 20-40% of the motoneurones; it is also unable to produce functional spermatozoa. As a step towards positional cloning of the wr gene, we have mapped the locus to proximal chromosome 11, thus excluding CNTF and its receptor as candidates, and suggesting the closely-linked Rab 1 gene encoding a GTP-binding protein as a possibility. In the case of the adr (arrested development of righting response) mouse, which shows hyperexcitability of mature muscle fibres due to a reduction of the 'dampening' function of chloride conductance at resting potential, we have shown that the defect is in the chloride channel gene adr/Clc-1 on chromosome 6. This allowed us to predict via synteny the chromosomal location of human Thomsen's and Becker's myotonias as close to the TCRB gene on human chromosome 7q. The combination of these approaches with gene-targeting approaches will allow genetic analysis of the establishment and structure of the neuromuscular system. PMID- 8008831 TI - Reverse genetics of the mouse central nervous system: targeted genetic analysis of neuropeptide function and reverse genetic screens for genes involved in human neurodegenerative disease. AB - The development of gene targeting technology in mouse embryonic stem cells allows reverse genetics to be used to investigate the function of any cloned gene in the developing and adult brain. Promoter-trap, replacement and insertion vector strategies can be used to generate defined mutations in the chromosomal copy of a cloned gene in embryonic stem cells. These cells can be used to make chimaeric mice, some of which transmit the in vitro mutation via the germline to transgenic offspring. The phenotype of complete loss-of-function mutations (gene knock-outs) can be studied at molecular, cell biological, neurophysiological and behavioural levels, and allows inferences about gene function to be made. Precise small mutations can also be made using integrative vector or two-step replacement vector strategies, allowing specific questions to be asked about regulation and protein structure-function relationships. Reverse genetics can therefore be used as an alternative or additional approach to pharmacology for the study of molecular functions in the central nervous system. Reverse genetic studies of the involvement of particular molecules in neurological disease syndromes may be superior to pharmacological studies to the extent that the syndrome is determined by genetic predisposition. The general ways in which reverse genetics of the mouse can be used to ask questions about molecules in the central nervous system are illustrated by examples from ongoing work of this laboratory. Neuropeptides are an important class of transmitters in the brain, but only in very few cases have specific CNS functions been assigned to a particular neuropeptide. Targeted mutation of neuropeptide precursor and receptor genes offers a rapid way to learn about neuropeptide function. Complete loss-of-function mutations will provide information on any developmental roles of a neuropeptide and on overall behavioural and physiological effects of loss-of-function. More specific targeted mutations allow dissection of the individual roles of multiple neuropeptides that derive from a common precursor protein, and allow in vivo studies of the functional importance of particular amino acids. Experimental progress towards targeted mutation of the neurotensin receptor is described as an example. Recent technological improvements makes targeted mutation of a number of genes possible. This allows reverse genetic screening to be undertaken for genes involved in particular neurobiological phenomena: genes are identified on the basis of molecular criteria (e.g. expression pattern), and gene-targeting used to check their relevance to a phenotype. Neurodegenerative disease is an important aspect of the human phenotype.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8008832 TI - Cellular and molecular approaches to neural repair in the medicinal leech. AB - Investigation of repair processes and the effects of damage in the leech has the advantage that it is possible to work with single neurons, and that leech neurons can regenerate. The effects of surface topology on neuronal outgrowth in culture were investigated using patterned substrates produced by photolithography. On grooved substrates with a depth, width and separation of 2 microns, the processes of cultured neurons showed significant alignment. In studies on regeneration, different mechanosensory neurons were shown to respond differently to lesions of their axons. High threshold units (N cells) respond by sprouting of additional processes from the axon hillock region within the CNS, whereas low threshold cells respond with a sprouting only at the lesion site in the nerve root and not within the CNS. Sprouted processes are retained for over a year. When a neuron of a particular modality is killed, cells of the same modality (but not the other) expand their receptive fields to cover the denervated skin. Single channel patch clamp recording experiments have been initiated on damaged neurons. Experiments are in progress to clone genes whose expression is regulated after peripheral nerve injury. PMID- 8008833 TI - cDNA libraries from a few neural cells. AB - One of the most powerful approaches to the molecular analysis of differential gene expression is to construct cDNA libraries corresponding to different tissues or developmental stages, and then to enrich for genes expressed in a particular tissue or at a particular time by subtractive hybridisation. Our aim is to reduce the complexity of neuronal cDNA libraries by generating libraries from the mRNA of a single cell. The system chosen is the Retzius cell of the leech, a large neurone which can be unambiguously dissected out. A cDNA library was generated from one leech ganglion (containing about 400 neurons) by anchor 1-oligo dT priming, the addition of dG tails, second strand synthesis primed by an anchor 2 oligo dC primer, followed by PCR from the two anchor regions. XBaI and EcoRI sites were included in the respective anchor primers, between the dT or dC run and the PCR primer sequence, allowing high-efficiency directional cloning. Eight clones picked and sequenced at random gave five with some homology to a known protein and three novel genes. The average insert size in the library was 600 bp, 0.2% of the clones hybridised to repetitive DNA, and 20/30,000 clones gave signals with the Drosophila actin gene. This approach has now been extended to a few pooled Retzius cells. PMID- 8008834 TI - Neurotrophin receptors. AB - The neurotrophins are members of a family of four related proteins that allow the survival and differentiation of specific sub-sets of embryonic vertebrate neurons. On neurons, two types of neurotrophin receptors can be distinguished on the basis of their dissociation constants: low affinity receptors (Kd 10(-9) M) and high affinity receptors (Kd 10(-11) M). Several genes coding for neurotrophin receptors have been cloned and the expression in fibroblasts of the recombinant membrane proteins allows comparisons to be made between the binding properties of the neurotrophins on such cell lines and neurons. As a result, it appears that much of the low affinity binding sites detected on neurons for all neurotrophins can be attributed to a single molecular entity, the low affinity neurotrophin (or NGF) receptor. This receptor binds all known neurotrophins with similar affinity but different binding kinetics. Its role in neurotrophic signal transduction remains to be established. In addition to this receptor, three members of the trk subfamily of tyrosine kinase receptors have recently been identified as receptors for the neurotrophins. These receptors (whose intrinsic tyrosine kinase activity can be stimulated by the various neurotrophins) bind the neurotrophins with higher affinity and higher ligand specificity when compared with the low affinity receptor. However, the observation has been made that some of the recombinant trk receptors on cell lines bind more than one neurotrophin (though typically with lower affinity than their own ligands).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8008835 TI - Molecular biology of glutamate receptors. AB - The ligand-gated receptors for L-glutamate play a central role in acute neuronal degeneration. Recently cDNAs have been isolated for subunits of several glutamate receptor subtypes. By sequence homology all these subunits clearly belong to one large gene family. Several subfamilies exist and match roughly previously pharmacologically and electrophysiologically defined subtypes of glutamate receptors. Currently four genes (GluR A, B, C and D) are known that code for the AMPA subtypes of glutamate receptors. Recombinant expression of wild type and mutated sequences identified a critical residue in the putative TM2 channel lining segment that controls Ca2+ ion permeability. The arginine (R) found in GluR B subunits at that position renders AMPA channels impermeable for Ca2+ ions, whereas glutamine (Q) containing GluR A, C and D subunits give rise to Ca2+ permeable channels. RNA editing converts the genomically encoded glutamine codon into the arginine codon found in GluR B cDNAs for the Q/R site. NMDA subtypes of glutamate receptors are formed after coexpression of the NR1 cDNA with a cDNA of the NR2 family. Depending on the member of the NR2 family used, NMDA receptors with different kinetical and pharmacological properties are generated. Common to all channels of these NMDA receptors is a high permeability for Ca2+ ions and a voltage dependent block by Mg2+ ions. All currently known NMDA receptor subunits have an asparagine at the Q/R homologous position. We found that this residue is critical for Mg2+ block and Ca2+ permeability of NMDA receptor channels. PMID- 8008836 TI - The aged care efficiency study. PMID- 8008837 TI - Case #10. Hemangioma of tongue. PMID- 8008838 TI - Infection control. Part 2: Update on CDC's guidelines for dentistry. PMID- 8008839 TI - Is the six-month recall a realistic interval of care? PMID- 8008840 TI - Disabilities Act gives protection to wide range of disabled workers. PMID- 8008841 TI - Comprehensive Dental Hygiene Care. Periodontal debridement. Part 2. PMID- 8008843 TI - Power brushes. PMID- 8008844 TI - Tender loving care. PMID- 8008842 TI - Dental hygiene celebrates 80 years of service. PMID- 8008845 TI - On a mission to Costa Rica. PMID- 8008846 TI - Laser technology: the future is now. PMID- 8008847 TI - We need a more accurate term for our role in perio therapy. PMID- 8008848 TI - Case #7. Parulis. PMID- 8008849 TI - Organizations establish standards for sterilization products, usage. PMID- 8008850 TI - When opportunity knocks.... PMID- 8008851 TI - 1993 RDH wages and benefits survey results. PMID- 8008852 TI - A regional analysis. PMID- 8008853 TI - Where do benefits fit in the picture? PMID- 8008854 TI - Money isn't everything ... or is it? PMID- 8008855 TI - Emergency drugs. PMID- 8008856 TI - Case #8. Skin cancer. PMID- 8008858 TI - Stuck in a rut? PMID- 8008859 TI - It's time to redesign the manual toothbrush. PMID- 8008857 TI - Professional liability. PMID- 8008860 TI - Sterilization monitors ensure patients' safety from disease. PMID- 8008861 TI - Could you recognize Lyme disease? PMID- 8008862 TI - Hospital offers perfect setting for RDH to help special patients. PMID- 8008863 TI - Case #9. Amalgam tattoo. PMID- 8008864 TI - Perfect posture. PMID- 8008865 TI - Making a difference. PMID- 8008866 TI - . . . Keep in touch. PMID- 8008868 TI - Cerebrovascular accidents. PMID- 8008867 TI - Comprehensive Dental Hygiene Care. Periodontal debridement. Part 1. PMID- 8008870 TI - Studies show similar results with surgical and non-surgical therapy. PMID- 8008869 TI - CDC updates infection control recommendations for dentistry. PMID- 8008871 TI - Case #2. Pleomorphic adenoma. PMID- 8008872 TI - Safety first. AB - As dental offices face more and more governmental regulations created to ensure the safety of staff members and patients, dental hygienists can take on a unique role by becoming the office safety manager. PMID- 8008873 TI - BOP scores are valuable index to evaluate individual needs. PMID- 8008875 TI - Answers clear confusion about surface disinfectants. PMID- 8008874 TI - Partners in prevention. PMID- 8008876 TI - Universal precautions are today's asepsis standards. PMID- 8008877 TI - Make breast cancer awareness a part of total patient care. PMID- 8008878 TI - Case #1. Giant cell fibroma. PMID- 8008879 TI - On their own. PMID- 8008880 TI - Antihypertensives. PMID- 8008881 TI - Glossary defines the true meaning of infection control. PMID- 8008882 TI - A historical look at infection control. PMID- 8008883 TI - Overhang removal should be integral part of debridement. PMID- 8008884 TI - [Magnetic resonance of the cartilages of the large joints]. AB - MRI of the articular cartilage requires a careful technical approach since this structure is very thin, with a peculiar internal architecture between the supporting matrix and the cell component. On MR images the normal articular cartilage has a zonal appearance. To optimize the variables for best visualization of the internal architecture of the hyaline articular cartilage, an ex vivo and in vivo study was carried out. Accurate T1 and T2 relaxation times of the articular cartilage were obtained with a particular mixed sequence and then used to create isocontrast intensity graphs. The latter allowed, in all pulse sequences (SE and GRE), the best combination of TR, TE and FA to optimize signal differences between cartilage areas. A trilaminar pattern was demonstrated, with a superficial and a deep hypointense areas, in all sequences, together with an intermediate area which was moderately hyperintense on SE images and markedly hyperintense on GRE images. In the current literature, MRI appears to have been widely used to investigate hyaline cartilage conditions. In many series, the technique proved its efficacy in assessing both acute (traumatic cartilage fractures, osteochondritis dissecans, arthritis) and chronic (arthrosis, chondromalacia patellae, Hoffa's disease, synovial plica syndrome) conditions of the articular cartilage. T2-weighted sequences (both SE and GRE) are widely known as the most accurate in assessing cartilage conditions, which depends mainly on the arthrographic effect of synovial fluid on T2-weighted images. Of late, also MR arthrography, especially MR arthrography after the i.v. administration of Gadolinium, has emerged as an outstanding technique to investigate articular cartilage conditions. On the basis of MR arthrography findings, some authors suggested a classification of osteochondritis dissecans, arthrosis and chondromalacia patellae on MR images. MR stages seem to be closely correlated with the histologic classification suggested for these conditions. PMID- 8008885 TI - [The SIRM (Italian Society of Medical Radiology) and the centennial of X rays. From history, a lesson for the future]. PMID- 8008886 TI - [Transjugular intrahepatic porto-systemic shunt (TIPS): indications and results]. AB - This study was aimed at describing some technical features of the transjugular portosystemic shunt (TIPS). December 1991 to November 1993, fifty-five TIPS were performed in our department. The right internal jugular vein, which is the most direct path to the inferior vena cava, was punctured in 48 cases, the left one in seven cases. The right suprahepatic vein was catheterized in 43 cases, and the median suprahepatic vein in 12 cases. The puncture of the portal vein was performed in 21 cases in the right portal branch, in the left one in 23 cases, and in the portal bifurcation in 11 cases. In all cases in which the puncture site was questionable, an X-ray exam with lateral or oblique projection was performed, to be sure that the needle had entered the intrahepatic portion of the portal vein. A landmark to locate the portal system, such as a catheter in the hepatic artery, a skin landmark or a metallic coil near the porta, were positioned in 30 patients. Particularly, in 20 patients, a 0.018-inch guidewire with platinum tip was placed at the bifurcation; in seven cases a 3F catheter was advanced over the guidewire, to visualize the portal bifurcation directly with contrast medium injection. In our experience, a total number of 83 stents were positioned in 55 patients: 53 Wallstents, 13 Palmaz stents, and 17 Strecker Nitinol stents. One single stent was placed in 31 patients, two stents in 21 patients, three stents in two patients, and, finally, four stents were positioned in one patient. In our series the technical success rate was 100%. The use of a metallic landmark significantly decreased procedures duration, ranging 40 minutes to 2 hours, and, above all, it allowed for significantly fewer puncture attempts, which varied from a minimum of 1-2 in 80% of cases, to a maximum of 20 especially in these patients with ascitis and with small and hard liver. PMID- 8008887 TI - [Transjugular intrahepatic portosystemic shunt (TIPS): indications and results after 22 months of experience]. AB - December 1991 through November 1993, fifty-five patients underwent TIPS with the following indications: failed sclerotherapy or surgery (25 patients), bleeding from gastric varices (3 patients), patients waiting for liver transplantation (11 patients) and refractory ascites (9 patients). Seven patients were included in a randomized TIPS vs sclerotherapy trial. The average follow-up of living patients is 4.6 months (range: 1-16 months). The technical success rate was 100%. The portosystemic gradient decreased from 22 mmHg to 10.7 mmHg. After TIPS all patients were followed-up with endoscopic, angiographic and color Doppler examinations and underwent periodic clinical checks. Early (5-day) angiographic follow-up exams showed partial stent thrombosis in 5/32 cases (15.5%) and complete stent thrombosis in 3 cases (9.3%). Late angiographic follow-up exams (1 9 months) showed complete stent occlusion in 2 cases, stent stenosis in 8 cases and hepatic vein stenosis in 5 cases. At present, 37 patients are alive (67%); 5 patients have undergone liver transplantation (9%), and 13 patients died (24%)--3 within 48-72 hours after the procedure and 10 in 1-8 months. Five patients had recurrent bleeding (9%). Ascites was reduced or disappeared in 8/9 cases. Early clinical complications occurred in 12% of cases and were treated with medical therapy. Within one year, signs of encephalopathy developed in 13 patients (23%) and were successfully treated with medical therapy. PMID- 8008888 TI - [Radiographic enlargement in the study of hand diseases. Digital versus conventional techniques]. AB - The electronic magnification of digital images was compared with direct digital magnification and with plain radiograph magnification. A whole-body computed radiographic system with photostimulable phosphor plates contained inside standard X-ray cassettes was used. The small bones of the hands and wrists of 18 patients with traumatic (10 cases) or degenerative (8 cases) bone conditions mainly due to chronic renal failure were studied. Each patient was examined with all three techniques: the images were retrospectively reviewed by four observers relative to resolution, contrast, visibility of the lesions and diagnostic value of each method. The statistical analysis of our results demonstrated better yield of direct digital magnification than of plain radiograph (p = 0.00043) and of electronic (p = 7.5 10(-13) magnification. This finding was mainly due to density and contrast optimization of digital images, in spite of their low spatial resolution. This feature allows good simultaneous representation of structures with different radiographic densities, as it happens in the hand and wrist. Electronic magnification yielded less brilliant results, even if compared with plain radiographic studies (p = 0.0032). However, this limitation was compensated for by the fact that this technique is easier and quicker to perform and that it does not require any additional X-ray exposure. PMID- 8008889 TI - [High resolution computerized tomography in the study of the lung parenchyma. Possibility of a low-dose protocol]. AB - High-resolution CT (HRCT) is a useful technique to investigate minimal diffuse lung disease. Two major limitations of HRCT are the higher radiation dose to the patient than in conventional CT of the chest and therefore the impossibility to study the lungs completely. These limitations can be partially overcome by using a low-dose protocol with mAs reduction. In our preliminary experience on 19 patients affected with various lung diseases, the low-dose protocol exhibited poorer image quality but almost equivalent anatomical detailing; the diagnostic yield was higher than that of conventional HRCT. Thus, in our experience, low dose HRCT makes an interesting compromise in the study of lung parenchyma. PMID- 8008890 TI - [Pulmonary involvement in scleroderma assessed with high-resolution computerized tomography and functional tests]. AB - This study was aimed at investigating and analyzing lung involvement in scleroderma patients with different imaging methods, toward a rational diagnostic approach. Twenty-four patients with systemic sclerosis were examined with pulmonary function tests (PFT), spirometry and diffusing capacity for carbon monoxide (DLCO), chest radiography and high-resolution Computed Tomography (HRCT). Abnormal findings were present in 42% of cases on X-ray films and in 71% of cases on HRCT images. PFT was abnormal in the spirometries of 42% of cases and in DLCO tests in 50% of cases. The most common findings at HRCT were the small reticular and the ground-glass patterns. HRCT emerged as the most effective method to evaluate lung involvement in systemic sclerosis. In our series, HRCT allowed possibly curable lung lesions to be differentiated from incurable ones. However, HRCT is suggested in the patients with impaired pulmonary function to allow treatment choice; on the contrary, in the patients with no functional impairment, HRCT adds little information to clinical findings, showing only limited focal lesions. PMID- 8008891 TI - [Characterization of hypertrophic cardiomyopathy with magnetic resonance]. AB - We selected 15 patients with hypertrophic cardiomyopathy (HCM) and 5 with secondary myocardial hypertrophy (SMH). All patients were examined by means of Magnetic Resonance Imaging (MRI) and echocardiography. The MR study was performed with gated T1- and T2-weighted spin echo sequences and cine MRI. We correlated echocardiographic and MRI measurements and found a correlation coefficient (R) of 0.72 for apex thickness, r = 0.84 for posterior wall thickness, 0.76 for the lateral wall and 0.89 for the area at papillary level. Cine MR acquisitions showed signal loss in the systolic phase at the outflow tract in 9 obstructive HCM patients, which was consistent with echocardiographic color Doppler findings. The signal intensity of myocardial tissue was analyzed with MRI. The values were correlated with those of the skeletal muscle. We performed the paired sample t test on T1- and T2-weighted spin echo sequences between the signal at the septum and that of the free wall in the 15 HCM patients. The analysis showed significant differences on T2-weighted sequences (p < 0.02). Unpaired t-test was performed between the 15 HCM and the 5 SMH patients; the analysis showed significant differences on both T1- (p < 0.01) and T2-weighted sequences (p < 0.04). PMID- 8008892 TI - [Magnetic resonance: preoperative assessment of abdominal aortic aneurysms. Comparison with surgical findings in 80 cases]. AB - This work was aimed at assessing Magnetic Resonance (MR) accuracy in the preoperative investigation of abdominal aortic aneurysms, with a view to suggesting MRI as the method of choice for surgical planning, replacing other relatively invasive investigation techniques like angiography and enhanced CT. In the last 3 years 80 patients with abdominal aortic aneurysms identified with US or CT were examined with 0.5-T MRI and underwent surgical repair within 15 days. Spin-echo (SE) T1-weighted axial, sagittal and coronal sequences were always performed. In 18 patients gradient-echo (GE) flow sequences were also acquired; SE T2-weighted sequences were used to study parietal thrombi in 10 patients and finally Gd-DTPA T1-weighted sequences were obtained in inflammatory aneurysms (3 patients). MR images were blindly evaluated by 2 radiologists. The following variables which are useful for surgical planning were considered for each patient: aneurysm extent, characteristics of parietal thrombi, dissections, fixurations, inflammation signs, involvement of renal arteries, vena cava, ureters, duodenum, the presence of retroaortic renal vein or of other anomalies or associated conditions. MR images were always compared with intraoperative findings, since surgery was considered as the gold standard. MR findings were in agreement with surgical findings in the evaluation of cranio-caudal aneurysm extent (78/80), parietal thrombus features (80/80), dissection (1/1) and fixuration signs (8/9), origin of renal arteries (80/80), inferior vena cava involvement (3/3), other anatomical anomalies or conditions (6/6). Inflammation signs were overestimated (14/8) as well as adhesion between aneurysm and duodenum (17/13). The presence of distal renal polar arteries was underestimated (2/4). In conclusion, MRI proves to be a highly sensitive method to demonstrate abdominal aortic aneurysms and is therefore suggested as the examination of choice before surgery. PMID- 8008893 TI - [Subpopliteal muscular venous thrombosis in aching calf syndrome]. AB - The lower limbs of 84 consecutive patients (48 women and 36 men, age range: 16-75 years, average: 38 years) suffering from acute aching calf symptoms were examined with conventional and color Doppler US. Thirteen cases of muscular thrombosis in the calf were observed, together with 19 cases of deep venous thrombosis, 7 post phlebitic syndromes, 9 lymphatic obstructions, 6 muscular hematomas and 7 popliteal articular cysts. Case history, clinical signs and phlebography do not allow the former condition to be differentiated definitely from the latter ones- especially hematomas and Baker's cysts which require different treatment protocols. The authors stress the value of conventional and color Doppler US imaging in the aching calf syndrome for its differential diagnostic capabilities. The other more complicated and expensive radiologic and laboratory techniques should be used in case of negative US findings only. PMID- 8008894 TI - [Diagnosis of free air in the abdomen. Role of echography]. AB - Pneumoperitoneum secondary to gastrointestinal tract perforation is usually detected with plain abdominal films. Even when the examination cannot be performed in the upright position, free abdominal gas can be demonstrated with the accurate evaluation of supine radiographs. Some literature studies showed the value of ultrasonography and its higher diagnostic yield than that of plain abdominal films. However, in our experience on a series of 37 patients with surgically confirmed post-perforative pneumoperitoneum who underwent US first and radiography second, US had lower sensitivity than radiography (76% vs 92%, respectively). This was only partially compensated for by the detection of other signs and by better etiologic orientation. Therefore, we believe plain abdominal films to be still the method of choice to study the patients with suspected gastrointestinal perforation. Thus, US should be used in selected cases only- i.e., clinical conditions preventing radiographs from being performed correctly, persisting clinical suspicion with negative or questionable radiographic findings, the exclusion of other acute abdominal conditions, and finally the presence of pneumoperitoneum in the patients referred for different clinical reasons. PMID- 8008895 TI - [Turbo-Spin-Echo sequences in focal liver diseases]. AB - Turbo Spin-Echo (Turbo SE) pulse sequences represent a new type of fast sequences characterized by a dramatic reduction in acquisition time with similar intrinsic contrast to that of conventional Spin-Echo (SE) pulse sequences. For a preliminary clinical comparison of turbo SE and SE sequences, a consecutive series of 25 patients with focal liver lesions was investigated by means of MRI at 1.0 T. The patients were selected on the basis of US or CT positive liver scans for focal lesions. All patients underwent MRI following the same protocol: axial T1-weighted (T1W) gradient echo (GE) sequences (TR/TE = 110/6 ms) with the "breath-hold" technique, T2-weighted (T2W) SE sequences (TR/TE = 1730/90 ms; FL = 60, M = 128 x 256, 2 AC, TA = 7 min 26 sec) and turbo SE sequences (TR/TE = 5100/112 ms, M = 240 x 256, 2 AC, TA = 2 min 48 sec). Slice thickness was 10 mm with a 1-mm gap in all cases. Qualitative (number, size and definition of the lesions) and quantitative (contrast-to-noise ratio (CNR) and relative CNR) variables were considered. SE and turbo SE sequences demonstrated the same number of lesions; the smallest lesion (3 mm) was identified by turbo SE sequences. Turbo SE sequences better depicted lesion margins than SE sequences. In all cystic conditions, CNR was higher in turbo SE than in SE sequences, while it was lower in all the extant conditions. This preliminary experience proves turbo SE pulse sequences to be a valuable tool in liver MRI, which calls for further clinical trials. PMID- 8008896 TI - [Ultrasonography and computerized tomography in the diagnosis of gallbladder carcinoma]. AB - The US and CT images of 40 surgical patients with histologically proved gallbladder carcinoma were retrospectively reviewed. The radiologic diagnosis was correct in 22 patients (55%). Gallbladder carcinoma patterns were: an intraluminal mass (type I) (7 patients, 17.5%), focal or diffuse wall thickening (type II) (5 patients, 12.5%) a mass replacing the gallbladder (type III) (10 patients, 25%). In 5 patients with type I or II gallbladder carcinoma, US and CT diagnosis was made easier by the presence of associated findings--i.e., liver infiltration and/or metastases, lymphadenopathy, dilated intrahepatic ducts, ascites. In 7 patients a gallbladder carcinoma was suspected in the presence of a small intraluminal mass (6 cases) or of focal wall thickening (1 case), with no stones and with dilated intrahepatic biliary ducts. In the extant 18 patients (45%) the radiologic diagnosis was: polyps (6 cases), stones with cholecystitis (11 cases) and empyema (1 case). US is the examination of choice in the diagnosis of gallbladder and biliary ducts conditions, but several diagnostic problems may arise in the differentiation from polyps and acute inflammatory disease. CT better demonstrates gastrointestinal tract invasion and lymphadenopathy, which can be a valuable finding for treatment planning. PMID- 8008897 TI - [Role of ultrasonography-guided fine-needle biopsy in the selection for surgical treatment in thyroid diseases. Multicenter retrospective study of 5,109 patients]. AB - FNAB cytology is a very specific diagnostic tool for distinguishing benign from malignant lesions. It allows the histologic type to be diagnosed too. FNAB findings also help select the type of surgery. The value of FNAB cytology was investigated in 5,109 patients examined from 1987 through March 1993. 607 patients has surgical confirmation. 444 patients underwent cytology before surgery, while 163 patients were not submitted to FNAB. Histology diagnosed 116 malignant tumors (19.2%): 83 of them were papillary carcinomas (71.5%), 26 follicular carcinomas (2.6%), 1 primary thyroid lymphoma (0.9%) and 3 medullary carcinoma (2.6%). Seventy-nine of 116 cases had been diagnosed by FNAB cytology, while 37 of 116 were diagnosed at surgery. Aspiration biopsy under US guidance reduced the rate of thyroidectomies from 19.2% to 8.5% because true-positive cases were assessed before surgery. FNAB cytology should be used as a preliminary diagnostic tool, thanks to its high accuracy and to its capabilities of distinguishing benign from malignant lesions for proper medical or surgical treatment. Moreover, FNAB cytology allows potentially malignant lesions to be surgically explored. PMID- 8008898 TI - [Role of Gadolinium-DTPA in the assessment of renal tumors with magnetic resonance]. AB - To investigate the role of Gd-DTPA in the MR study of renal cancers, 30 patients affected with primary (28) or recurrent (2) renal cancers were submitted to high field MRI (1.5 T). T1- and T2-weighted and Gd-DTPA-enhanced T1-weighted sequences were always acquired. Based on qualitative and quantitative criteria (calculation of the signal-to-noise ratio in the tumor mass and of the signal-difference-to noise ratio between tumor and renal parenchyma), Gd-DTPA influence was studied on the following variables: signal intensity and tumor demonstration, detectability of morphostructural features of tumor tissue and staging accuracy. As for the latter variable, MR results were compared with the results of anatomical and surgical staging (28 cases). Relative to unenhanced T1- and T2-weighted sequences, on Gd-DTPA-enhanced sequences 80% of the lesions were markedly hypointense relative to renal parenchyma and they were better demonstrated in 93% of cases. The S/N and the SD/N ratios were higher on Gd-DTPA-enhanced than on unenhanced images. After Gd-DTPA administration, the intratumoral necrotic areas, the walls and the septations of the cystic masses and the boundaries between tumors and renal parenchyma were better demonstrated. Staging accuracy was the same (90%) on both Gd-DTPA-enhanced T1-weighted and unenhanced images. Therefore, Gd-DTPA, although failing to increase staging accuracy, improves tumor depiction and demonstrates the morphostructural features of the mass. Since Gd-DTPA caused no side-effects, Gd-DTPA-enhanced T1-weighted sequences can replace T2-weighted sequences, whose acquisition time is definitely longer. PMID- 8008899 TI - [Thin-section computerized tomography of the kidney in the differential diagnosis of small tumor and cystic hypodensities]. AB - Small hypodense renal lesions with a round shape are frequently detected on CT scans of the upper abdomen after contrast medium administration. In nearly all cases these round hypodensities are simple small cysts with no clinical significance. However, the fluid density of these cysts cannot be always defined, due to the partial volume averaging which occurs on CT when 10-mm-thick slices and contrast enhancement are used. Therefore, a malignant tumor--i.e., small renal tumors or metastatic lesions--cannot be ruled out in some cases. Since the limitations of CT are related to partial volume averaging, the authors used both 5-mm and 10-mm slices to reduce this artifact. Forty-eight small hypodensities (< 15 mm) were studied after contrast agent administration: 42 of them were simple cysts and 5 were tumoral lesions--i.e., 3 renal cell carcinomas and 2 lymphomatous lesions. The results showed that, with 5-mm slices, the density of the fluid hypodensities decreased in nearly all cases and in 81.3% of cases it was below 30 HU. The difference in densities between 10-mm and 5-mm slices was about 50 HU (75 +/- 30 to 21 +/- 16 HU). In the 5 tumoral hypodensities, lesion density was still in the soft tissue range also with 5-mm slices, with no major decrease. These results show that this technique is simple and effective in the differential diagnosis of small renal hypodensities since it requires only a short additional examination time. PMID- 8008900 TI - [Survival and recurrence of endometrial adenocarcinoma]. AB - 444 endometrial carcinomas were retrospectively reviewed. Disease-free survival (DFS) was 83.6% at five years and 80.5% at ten years. 349 T1 cancers were treated by TAH-BSO and post-operative irradiation; 22.6% of them were over-staged. DFS ranged from 100% to 91% in 270 low-risk T1 patients, dropping to 84% in intermediate risk patients and to 44% in high-risk patients. DFS was 93% and 66% in the patients overstaged as pT2 and pT3, respectively; it was 82% for ovarian spread and 45% for pelvic peritoneum/parametrium invasion. T2-T3 patients were treated with preoperative irradiation and bilateral hysterectomy. DFS was 90.5% vs. 72.2% and 2/2 vs. 3/7 when the lesion was understaged. The results of irradiation were similar to literature data, but 53% of patients (all in poor general conditions and/or very old) died from associated diseases. Relapses were observed in 13.6% of cases (62/444 patients); 29 (6%) were local recurrences and 33 (7.6%) were distant metastases, which correlated well with recurrences and 33 (7.6%) were distant metastases, which correlated well with risk factors. Severe complication (G3) were observed in 6.3% of cases. PMID- 8008901 TI - [Scintigraphy with gallium-67 citrate in patients with AIDS: pathologic extrapulmonary uptake]. AB - 67Gallium citrate can accumulate in different inflammatory and neoplastic lesions. The mechanisms of 67Gallium uptake in abnormal tissue are still partially unknown and the tracer is considered a nonspecific indicator of disease. In AIDS patients, 67Gallium citrate is used in the diagnosis and characterization of opportunistic pulmonary infections and especially of Pneumocystis carinii pneumonia. From June 1989 through December 1992 in our Department 140 67Gallium scans were performed on 103 AIDS patients, referred for evaluation of pulmonary symptoms. All studies were carried out 72 hours after i.v. administration of 185 MBq 67Gallium citrate, with anterior and posterior views of head, chest and abdomen. The images were evaluated with conventional diagnostic criteria and site, number and intensity of abnormal foci of extrapulmonary uptake were recorded. Abnormal extrapulmonary uptake was found in 17 patients (12%): gastric (3, two of which also exhibited abnormal intestinal uptake), esophageal (1) hepatic (1), intestinal (2) renal (4), nodal (3), ocular (1), cutaneous (1), sinusal (1) localizations. In all cases clinical, endoscopic, bioptic or microbiological demonstration of the possible cause of 67Gallium uptake was obtained. An intriguing finding in our series was the lower incidence of gastric uptake (two patients with miliary tuberculosis and one patient with gastric candidiasis) than in the literature. This finding could be explained by clinical and epidemiologic differences between different patient populations. However, the scan interval after tracer administration should be also taken into account, since in our study scans were always performed at 72 hours, while in other series the interval ranged 24-48 hours. The relatively high incidence of abnormal extrapulmonary uptake confirms the opportunity of whole body exploration after 67Gallium administration in the patients with such multisystemic disease as AIDS, even when the patients are referred mainly for respiratory problems. PMID- 8008902 TI - [Scintigraphy with iodine-131 metaiodobenzylguanidine in the study of paraganglioma. Comparison between benign and malignant tumors]. AB - In order to evaluate 131I metaiodobenzylguanidine (MIBG) uptake in patients with benign or malignant paragangliomas, 28 patients (14 men and 14 women, mean age 37 +/- 10 years) with benign (no. = 15; group 1) or malignant (no. = 13; group 2) tumors underwent MIBG scintigraphy. A total of 110 lesions (20 benign and 90 malignant) were studied. In all patients histologic disease confirmation was obtained. MIBG uptake was quantified on 48 hours' images (Kodak NMC-1 films) using a photographic densitometer. The optical densities of tumor and adjacent or contralateral normal tissue were used to calculate the MIBG uptake intensity ratio for each lesion. In group 1, all patients exhibited 1 or 2 lesions with abnormal MIBG uptake. In group 2, all patients had 1 to 28 abnormal foci of MIBG uptake. In the patients with 2 or more lesions, the average MIBG uptake intensity ratio was calculated. MIBG uptake intensity ratio was significantly higher in malignant than in benign paragangliomas (5.2 +/- 2.4 vs 2.9 +/- 1.4, p < 0.01). Since MIBG uptake in paragangliomas reflects the intratumoral concentration of catecholamines, higher MIBG uptake in malignant lesions suggests a greater amount of stored catecholamines in these tumors. In conclusion, 131I MIBG scintigraphy may be useful to distinguish benign from malignant paragangliomas. PMID- 8008903 TI - [Computer-assisted combined management of physical radiation protection and quality control of X-ray diagnostic equipment]. AB - A software for the computer-assisted management of radiation protection and quality control of radiodiagnostic equipment is described. The code was written in DB3-plus language. In addition to some independent archives on X-ray diagnostic systems identification, it includes technical and radiation protection checks, environmental dosimetry in the controlled areas and on workers. The data can be searched through a key field and periodical radiation protection reports and action reports can be printed. The software programs can also perform some "intelligent" operations such as the calculation of controlled areas range and the classification of X-ray diagnostic systems and workers. This is done by retrieving the information from the archives. The software can be updated, revised and modified very easily, due to the non-connection of the archives. It is also very simple to connect DB3-plus archives with many other software packages to process and elaborate data. This software is the core of an integrated system we are developing to store and process data from diagnostic X ray systems control meters and from our TLD personal dosimetry equipment. PMID- 8008905 TI - [Intraosseous lipoma of the calcaneus. Report of a case identified with magnetic resonance]. PMID- 8008904 TI - [Role of magnetic resonance imaging in the diagnosis of cerebral systemic lupus erythematosus. Report of a case]. PMID- 8008906 TI - Juvenile rheumatoid arthritis with unusual X-ray appearance. A case report. PMID- 8008908 TI - [Combined diagnostic assessment of a case of giant pseudoaneurysm of the gastroduodenal artery]. PMID- 8008907 TI - [Unusual form of neoplasm of the breast: aggressive fibromatosis. Report of a case]. PMID- 8008909 TI - [Report of a case of aneurysm of the right branch of the portal vein examined with echo-color-Doppler]. PMID- 8008910 TI - [Primary non-Hodgkin's lymphoma of the spleen. Report of a case examined with computerized tomography]. PMID- 8008911 TI - [Imperforate hymen. Unusual cause of fetal hydroureteronephrosis]. PMID- 8008912 TI - [Synovial sarcoma of the posterior mediastinum. Report of a case]. PMID- 8008913 TI - Respiratory syncytial virus (RSV) bronchiolitis: comparative study of RSV groups A and B infected children. AB - The grouping characteristics of 29 respiratory syncytial virus (RSV) present in nasopharyngeal cells collected from hospitalized children with bronchiolitis during the 1990 RSV season in Porto Alegre, RS, were analysed. Twenty-two were grouped as belonging to group A and 7 to group B. Cyanosis, oxygen therapy, cough, length of hospitalization and atelectasis were observed to be more frequently found within group B infected children. Other clinical signs and symptoms were similarly found in both groups. PMID- 8008915 TI - Pig bite in Brazil: a case series from a teaching hospital. AB - A retrospective survey done from 1987 till 1990 revealed that 23 patients bitten by pigs sought medical help at a teaching hospital in Uberlandia, in southeastern Brazil. Most cases (21) were from Uberlandia. The cases were evenly distributed by month and by year; most of them (14/16; 87.5%) occurred between 7.00 a.m. and 7.00 p.m. The male to female ratio was 6.7:1. Age ranged from 6 to 73 (mean 38.95 +/- SD 22.06, median 36). The bites were more common on the upper limbs, particularly on the forearms. In 11 (47.8%) cases the injury was described as deep. In most cases where information was available the injury was related to capture, transport or immobilisation of the pig for slaughter. The following medical procedures were performed: local cleansing in 19(82.6%) cases, rabies vaccine (12; 52.2%), antirabies serum (2; 8.7%), suturing (6; 26.1%) and tetanus vaccine (12; 52.2%). There was no case of infection at the bite site, neither of rabies or tetanus. By our data, the annual incidence of pig bite in Uberlandia can be estimated to be about 1.5/100,000. PMID- 8008914 TI - [The evaluation of ketoconazole in mice inoculated with Paracoccidioides brasiliensis by liver and spleen histopathology and by the intradermal paracoccidioidin reaction]. AB - Male albino mice were inoculated intravenously with 0.5 x 10(7) viable yeast forms of P. brasiliensis (strain 2052). These animals were treated with two doses of ketoconazole (50 and 100 mg/kg) during fifty days and the sacrificed. We studied the presence of P. brasiliensis, the inflammatory granulomatous response of liver and spleen and the anti P. brasiliensis delayed hypersensitivity response measured by the footpad test after 48 hours. It was observed that: 1. animals infected and treated with ketoconazole showed reduction in the number of fungi in the organs studied; 2. there was no difference in the number of granulomas among animals treated and non-treated; 3. the cutaneous delayed tests intensity was similar in all animals. PMID- 8008916 TI - Effects of severe protein restriction in levels of parasitemia and in mortality of mice acutely infected with Trypanosoma cruzi. AB - Adult mice were submitted to different degrees of protein restriction for five weeks (4.75, 9.5, 14.25 and 19% of protein in isocaloric diets with normal content of mineral and vitamins), being subsequently infected with two strains of Trypanosoma cruzi: 10(5) trypomastigotes of Y strain or 10(4) trypomastigotes of CL strain. The same diet was maintained for all animals and the infection was followed up by evaluation of blood parasites, mortality and intensity of lesions in the heart and skeleton muscle. Only severe protein restriction (4.75%) induced decrease in resistance to the infection with both the Y and CL strains of T. cruzi, which resulted in higher parasitemia and mortality. The inflammatory lesions in heart and skeleton muscle were less extensive in groups with severe protein restriction despite the increased number of parasite in muscle cells. Depression of immune mechanisms could be responsible for the reduced resistance and reduced inflammatory reaction after T. cruzi infection in severely protein restricted animals. PMID- 8008917 TI - [Tests of inflammatory activity in endemic pemphigus foliaceus]. AB - Endemic pemphigus foliaceus (EPF) has its pathogenesis frequently associated to autoimmune phenomena. In this paper, a few routine laboratory tests, usually disturbed in some autoimmune diseases, were taken in 20 patients with EPF, which were screened for antinuclear antibodies (ANA), rheumatoid factor (RF), C reactive protein (CRP) and changes of erythrocyte sedimentation rate (ESR), serologic proteins electrophoresis and total leucocyte count. The CRP was found in 60% of cases, leukocytosis in 85%, high ESR in all of them and mild alterations in serologic proteins analysis. No ANA or RF was found. Although widely accepted as nonspecific tests, we believe that an association of the laboratory routine tests with clinical findings, can prove to be helpful in the follow up care of these patients. PMID- 8008918 TI - [Fever of unknown origin: guidelines, clinical clues and complementary examinations]. PMID- 8008919 TI - Leptospirosis patient with AIDS: the first case reported. AB - A case of renal icterohemorrhagic leptospirosis involving a patient with acquired immunodeficiency syndrome (AIDS) is reported. Despite the low levels of CD4+ T lymphocytes, the clinical course of leptospirosis was similar to that observed in non-immunodepressed patients, and no worsening of AIDS occurred due to the infection by the spirochete. Serologic conversion was observed in the microscopic agglutination test, with maximum titer of 1:3,200. The patient had positive urine cultures for Leptospira interrogans for two months, whereas blood cultures were negative. PMID- 8008920 TI - [2 cases of paranasal aspergilloma due to Aspergillus niger]. PMID- 8008921 TI - [Leptospirosis in children in Rio do Janeiro]. AB - In order to obtain data about clinical manifestations of symptomatic leptospiral infection in children, the authors reviewed 188 microscopic agglutination tests performed on sera of patients aged 0 to 12 years, made at the National Reference Laboratory of Leptospirosis (FIOCRUZ-RJ) from January 1983 to June 1991. Fifty two (27.6%) sera were positive. Twenty three (12.2%) children had serological evidence of acute infection. The most frequent signs and symptoms of these 23 cases were: fever (100%); myalgia (69.5%); headache (52.1%); jaundice (47.8%); vomit (34.8%); abdominal pain, hemorrhagic manifestations and impaired renal function (17.4%); conjunctivitis (13%); hepatomegaly (4.3%). PMID- 8008922 TI - Time for Congress to embrace risk analysis? PMID- 8008923 TI - Leukemia risk associated with benzene exposure in the pliofilm cohort: I. Mortality update and exposure distribution. AB - The National Institute of Occupational Safety and Health (NIOSH) recently completed a vital status update adding 6 years of observation on the rubber workers known as the Pliofilm cohort. Using traditional standardized mortality ratio (SMR) analysis, we investigate the impact of the additional information gathered in the NIOSH update. We also compare the effect of using three sets of job-, plant-, and year-specific exposure estimates on the evaluation of benzene's leukemogenicity. The lack of any additional cases of multiple myeloma does not support trends toward elevated risks for this endpoint (as had been observed earlier), and there is no indication of increased incidences of solid tumors (as predicted by animal studies). Qualitatively, which exposure estimates are used does not alter the conclusions. The data added in the update did not greatly modify the estimated relative risk of leukemia associated with benzene exposure, but did confirm previous findings that occupational exposure to high concentrations had leukemogenic potential. The fact that leukemia has not been observed in any individual who started employment in Pliofilm production after 1950 suggests that the observed leukemia cases could be a response to very high levels of benzene exposure that occurred during the early years of this manufacturing process. PMID- 8008924 TI - Leukemia risk associated with benzene exposure in the pliofilm cohort. II. Risk estimates. AB - The detailed work histories of the individual workers composing the Pliofilm cohort represent a unique resource for estimating the dose-response for leukemia that may follow occupational exposure to benzene. In this paper, we report the results of analyzing the updated Pliofilm cohort using the proportional hazards model, a more sophisticated technique that uses more of the available exposure data than the conditional logistic model used by Rinsky et al. The more rigorously defined exposure estimates derived by Paustenbach et al. are consistent with those of Crump and Allen in giving estimates of the slope of the leukemogenic dose-response that are not as steep as the slope resulting from the exposure estimates of Rinsky et al. We consider estimates of 0.3-0.5 additional leukemia deaths per thousand workers with 45 ppm-years of cumulative benzene exposure to be the best estimates currently available of leukemia risk from occupational exposure to benzene. These risks were estimated in the proportional hazards model when the exposure estimates of Crump and Allen or of Paustenbach et al. were used to derive a cumulative concentration-by-time metric. PMID- 8008925 TI - Environmental hazards in the Chinese public's eyes. AB - The People's Republic of China suffers each year from various environmental hazards. Although risk perception study has a 40-year history in Europe and North America, little is known about risk perception in China. Previous studies of risk perception have primarily focused on unnatural hazards, but China has experienced many natural environmental hazards. Therefore, the Chinese public's perceptions of environmental hazard risks must be considered in order to support the IDNDR program. The Chinese public's perceptions of environmental hazards are similar to those of Europeans and North Americans, but different characteristics are observed. PMID- 8008926 TI - Natural disasters in the United States as release agents of oil, chemicals, or radiological materials between 1980-1989: analysis and recommendations. AB - Generally, hazards research and literature has treated natural and technological disasters as separate entities. This study attempts to determine how frequently interaction between these two types of disaster took place in the United States from 1980-1989. Data were collected by performing a literature review, contacting organizations and individuals active in hazards research and mitigation, and through a questionnaire sent to the emergency management agencies of all 50 states. The consensus derived from the data is that the number of incidents where natural and technological disasters interact is rising while preparations, which recognize the complications inherent in such combined events, remain cursory. There is a pressing need for states to record, and make available to managers, information regarding the number of combined natural/technological events affecting their areas. Only when such data are available will it be possible to make appropriate decisions regarding the best way to reduce the effects of a natural disaster causing a catastrophic release of hazardous materials. PMID- 8008927 TI - Assessing the relationship between environmental lead concentrations and adult blood lead levels. AB - This paper presents a model for predicting blood lead levels in adults who are exposed to elevated environmental levels of lead. The model assumes a baseline blood lead level based on average blood lead levels for adults described in two recent U.S. studies. The baseline blood level in adults arises primarily from exposure to lead in diet. Media-specific ingestion and absorption parameters are assessed for the adult population, and a biokinetic slope factor that relates uptake of lead into the body to blood lead levels is estimated. These parameters are applied to predict blood lead levels for adults exposed to a hypothetical site with elevated lead levels in soil, dust and air. Blood lead levels ranging from approximately 3-57 micrograms/dl are predicted, depending on the exposure scenarios and assumptions. PMID- 8008928 TI - Dose-response assessment of airborne methyl isothiocyanate (MITC) following a metam sodium spill. AB - A tank car derailment in northern California in 1991 spilled metam sodium into the Sacramento River, and released its breakdown product, methyl isothiocyanate (MITC), into the air. This paper describes the risk evaluation process used. Over 240 individuals reported symptoms such as eye and throat irritation, dizziness, and shortness of breath. Reference exposure levels (RELs) for 1 hr were developed for MITC and compared to exposure concentrations. Ocular irritation in cats was the most sensitive endpoint reported. The no observed adverse effect level (NOAEL), divided by an uncertainty factor (UF) of 100, produced an REL of 0.5 ppb of MITC in air to prevent discomfort. An REL to prevent disability was estimated to be 40 ppb. An REL to prevent life-threatening injury was estimated to be 150 ppb. Measured MITC levels ranged from 0.2-37 ppb and estimated peak levels ranged from 140-1600 ppb. The usefulness of RELs for emergency planning is discussed. PMID- 8008929 TI - A hint of risk: tradeoffs between quantitative and qualitative risk factors. AB - Risk-perception research plays an active role in discussion of risk-management alternatives. However, little guidance is provided regarding how public concerns should be weighed against other sources of cost and benefits. This paper reports the results of two experiments that measure tradeoffs among cost (in dollars), a quantitative risk measure (number of deaths or injuries), and several qualitative characteristics associated with perceived risk. Most subjects were willing to make the requested trade. However, the perceived risk information led others to reject the proposed technology. PMID- 8008930 TI - One agency's use of risk assessment and risk communication. AB - Few organizations have the courage to evaluate their own use of risk assessment (identifying hazards and estimating their probability and magnitude) and risk communication (interacting with internal and external stakeholder groups about risks). The USDA Animal and Plant Health Inspection Service (APHIS) wants to enhance its overall risk analysis process for managing a wide range of risks to animals, plants, and human health. We gathered survey data for a baseline of APHIS professionals' understanding and use of risk assessment and risk communication. APHIS professionals spend a surprisingly large share of their time communicating about risks. They perceive that risk estimates influence decisions, but that risk estimates should have more influence. Respondents reported little opposition to APHIS risk management decisions, and little use of channels such as USDA Extension Service for disseminating risk messages. Substantial variance across responses is explained mostly by differences in the roles of the 11 work units (now 10) within the agency. Location also contributes to the variance. Demographic variables seem less important. PMID- 8008931 TI - [HTLV-II infection in parenteral drug addicts from western Andalucia]. AB - The epidemiology of retrovirus HTLV-II is scarcely known even though it appears to be narrowly related to parenteral drug addiction. In order to find out the prevalence of HTLV-II among IVDU in our area, the sera of 137 subjects who came to our center for clinical evaluation were analyzed. The presence of HTLV-I/II antibodies were determined via ELISA and the sera that were repeatedly reactive were confirmed by the Western blot technique which reveals infection by both retroviruses. Two sera were repeatedly positive by ELISA (1.45 percent). Western blot confirmed HTLV-II positivity in both sera. Serology for HIV-1 was positive in 52 sera (37.9%). The two HTLV-II positive sera were also positive for HIV-1. These results indicate that HTLV-II infection is already present in the IVDU population in our area, where, similar to what happens in the U.S. and Europe, this retrovirus is implicated in the majority of HTLV infections in IVDU. PMID- 8008932 TI - [Abdominal mass in a young woman]. PMID- 8008933 TI - [Atypical presentation of a mucinous bronchioalveolar carcinoma]. PMID- 8008934 TI - [Nutrition and cardiovascular diseases in elderly people]. AB - Older age is a vulnerable stage from the nutritional point of view. Nutritional deficiencies are frequent and their consequences serious. That is why restricting diets are dangerous and must be considered with precaution. Though in developed countries the number of elderly people is increasing, the treatment of cardiovascular diseases in this age group is based by extrapolating the recommendations set for adults of minor age, and this may be not correct. High cholesterol and saturated fat intakes are recognized as harmful, but diet restrictions can lead to other nutritional deficiencies that can be damaging in relation to cardiovascular diseases. To improve the diet can be of great help in this sense. Diet restrictions concerning one or more foodstuffs must be introduced with caution and control, watching the nutritional status of the elderly person. It must be avoided that the fight against cardiovascular diseases may lead to other nutritional deficiencies with similar or worse sanitary repercussions. PMID- 8008935 TI - [Choice and use of the new antifungal agents]. PMID- 8008936 TI - [Oxygen therapy: when, how much, and how]. PMID- 8008937 TI - [Pneumococcal endocarditis and Pneumocystis carinii pneumonia in a patient with HIV infection]. PMID- 8008938 TI - [Prolonged survival in patients with progressive multifocal leukoencephalopathy associated with AIDS treated with high doses of zidovudine]. PMID- 8008939 TI - [AIDS in the elderly]. PMID- 8008941 TI - [Clinical and prognostic importance of extraenteral infection of Salmonella non typhi. A new classification]. PMID- 8008940 TI - [Tuberculous pericarditis. Clinical aspects in patients with or without AIDS]. PMID- 8008942 TI - [Human immunodeficiency virus infection and tuberculosis: who should receive chemoprophylaxis?]. PMID- 8008944 TI - [Decision regarding chemoprophylaxis with isoniazid in patients using parenteral drugs and infected with HIV]. AB - OBJECTIVES: Analyze the decision to enact or to refrain from chemoprophylaxis (CP) with isoniazide (INH) in patients who are intravenous drug users (IVDU) in Spain infected by the human immunodeficiency virus (HIV), either classified or not with hypersensitive skin tests. METHODS: With the bibliographic information available and the help of decision tree, an analysis of the effectiveness and of the consequences of drug costs of CP with INH in those patients is performed. RESULTS: Overall, the HIV+ IVDU benefit from CP is an increase in survival of 80 days, with a savings of 7,252 pesetas per patient. The intradermal reaction with PPD and the retarded hypersensitivity tests (HCR) allow us to classify them in three subgroups: a) PPD+ where CP is universally admitted and thus corroborates our study; b) PPD-/HCR- where CP increases survival 201 days and saves 20,616 pesetas per patient; and c) PPD-/HCR+ where survival is increased 33 days and the pharmacological costs increase 1,536 pesetas per patient under CP. CONCLUSIONS: For the present situation in Spain, CP with INH is effective in HIV+ IVDU patients, independent of the results of the intradermal reaction skin tests. PMID- 8008943 TI - [Salmonella ssp non-typhi focal infections]. AB - Provided here are the descriptions of 18 patients with focal infections caused by Salmonella spp no-typhi occurring in a period of seven years at the Puerta de Hierro Clinic. In all cases, there was at least one local factor, treatment, or underlying illness associated with decreased resistance to infection. Antecedents of severe gastroenteritis were found in seven cases (38 percent). Eighty-three percent had previous or concomitant bacteremia caused by the same serotype of Salmonella isolated in the focal infection. S. enteritidis was the most prevalent serotype (66 percent). The most common localizations were plueropulmonary (5), osteoarticular (5), and intravascular (3). Relapsing infection was demonstrated in five cases. There was 28 percent mortality. Statistically, age greater than 65 years and the absence of surgical intervention were associated with a worse prognosis. PMID- 8008945 TI - [Clinical characteristicsand course of extrapulmonary/disseminated tuberculosis in patients with AIDS. Study of 103 cases diagnosed in the province of Cadiz]. AB - Tuberculosis constitutes a public health problem that has become more serious in the past couple of years primarily due to the pandemic of human immunodeficiency virus (HIV). This study analyzes the evolutionary, clinical, and epidemiological characteristics of the extrapulmonary and disseminated forms of tuberculosis (TBD/E) in AIDS patients diagnosed in the province of Cadiz. Data for 103 patients who manifested both diseases were gathered prospectively. The prevalence of TBD/E was 30 percent among patients with AIDS. The primary risk factor was addiction to parenteral drugs (91 percent). Seventy-five percent of the patients were diagnosed with disseminated forms of the illness and 25 percent with extrapulmonary forms. The organs affected tended to be lymphatic ganglions and the lungs. Worthy of note is the lateness in seeking medical attention (45.6 +/- 4.5 days; range: 4-240 days). We conclude that tuberculosis constitutes a common pathology with an appreciable mortality in AIDs patients. Disseminated forms of tuberculosis predominate and may adopt a wide range of clinical manifestations. The lateness with which patients seek medical attention is a fact worth emphasizing. PMID- 8008946 TI - [The influence of the arterio-alveolar gradient of carbonic dioxide and of the real value of respiratory gas exchange on the estimation of alveolo-arterial gradient of oxygen]. AB - In 46 patients with diverse respiratory alterations, the alveolus-arterial gradient for oxygen (PA-aO2) was calculated from a simplified equation and from the complete equation of alveolar gas. In order to be able to apply the latter, the composition of expired air, ventilation, and capnogram was measured in each patient upon taking an arterial blood sample. These values are later used in determining the alveolar fraction of carbon dioxide (CO2) and thus, calculate the PA-aO2 from the complete equation for alveolar gas. The values for PA-aO2 estimated from this equation were greater than those derived from the simplified equation. With the latter, the PA-aO2 was underestimated in 36 percent of the patients with abnormal respiratory function. This underestimate is due to the fact that, in the simplified equation, both the possible variability of respiratory exchange (R) as well as increases in the arterio-alveolar gradient of CO2 (Pa-ACO2), as commonly found in patients with bronchopulmonary problems are taken into account. The high percentage of falsely normal gradients for O2 found in our study, we believe, may justify, at least in some cases, the calculation of PA-aO2 from the complete equation, and thus, the measurement of alveolar pressure for CO2 upon arterial blood sample extraction for gasometry. PMID- 8008947 TI - [Reflections on the teaching experience of an emeritus professor]. PMID- 8008948 TI - [Diagnosis of arterial hypertension: automatic ambulatory monitoring or conventional techniques?]. PMID- 8008949 TI - [Influence of meat consumption in relation to various cardiovascular risk factors in the elderly]. AB - It has been analyzed food intake, energy and nutrients, Quetelet index, blood pressure and lipid profile in 180 elderly people from Madrid (71 institutionalized and 109 free-living), in order to get the relationship between meat intake (< 150 or > or = 150 g/day) and the different risk factors from cardiovascular disease and other foodstuff intake. Those elderly people who eat 150 g/day or more (AC) take more food in general. There is a significant difference for meat and cereals, eggs, fruits, beans, and fish products. They have only a poor intake of dairy products when comparing with those who eat less than 150 g/day (BC). As a result of these differences in food habits, the AC group has a superior intake of energy and most part of other nutrients. Nevertheless, it was only significant the difference for the niacin and for percentage of energy derived from saturated fatty acid. There are no significant differences in blood pressure. AC elderly have more Body Mass Index and show serum lipids more satisfactory than the BC ones. High meat intake is not related to high risk from cardiovascular diseases in our elderly people group. The reason is that this high intake is associated with a better intake of other foods which give them, in general, a better nutritional status (with better intake of vitamins related to lipidic metabolism) which may be observed at biochemical level. PMID- 8008950 TI - [Influence of the place of measurement and of the person who performs it on the control and diagnosis of arterial hypertension]. AB - The use of ambulatory monitorization of blood pressure has shown the importance of the alarm reaction or white coat reaction and its conditioning factors in some patients. The influence of place (medical facility or home) and person who performs the procedure (doctor or nurse) on the taking of blood pressure is studied with regard to degree of control and/or disease diagnosis. The design is descriptive with a cross-section analysis. The sample is made up of 100 people-50 with hypertension and 50 who came to the center for reasons unrelated to blood pressure and were selected at random. Of the results obtained, the findings below are noteworthy. The number of controlled hypertension cases is fewer in the medical consultation (18 percent) or with nursing staff (22 percent) than in the patients' homes, whether the procedure is performed by the doctor (54 percent) or by the nurse (58 percent) (p = 0.000004). In the group of individuals who sought consultation, the number of hypertension cases detected by random measurements is fewer in the medical consultation (66 percent) than by the nursing staff (48 percent) and lowers significantly at home (p = 0.000001), whether taken by the doctor (22 percent) or by the nurse (20 percent). It is confirmed that figures for blood pressure at home are lower than those registered in the consultation, be they taken by the doctor or the nurse. We believe that the elevation in blood pressure is not exclusively attributable to the doctor and suggest that place where the procedure is performed is more important than the person who performs the procedure. PMID- 8008951 TI - [Validity of epidemiologic criteria in the detection of hypertension]. AB - We wish to find out the quality of the diagnostic test commonly used in epidemiological studies to detect hypertension, and in so doing, we study the validity of epidemiological criteria in the detection of hypertension (diagnostic test) and compare the diagnostic thresholds of the World Health Organization (WHO) and the Joint National Committee (JNC). Two methods of detection for arterial hypertension are used in this study of 674 people. One is population based (mobile unit), and the other is opportunistic sampling. (systematic measurements of blood pressure in medical consultations). As a test of certainty, clinical confirmation is performed. The methodology of Haynes and Sackett is used in the validation study. The epidemiological criteria obtains a sensibility of 90.4 percent and a specificity of 94.4 percent with the diagnostic thresholds of WHO, and a sensibility of 97 percent and a specificity of 81.2 percent with those of JNC, which are defined as effective methods of screening in the detection of hypertension. The excess prevalence of HBP obtained using the diagnostic criteria of WHO is 4.5 percent (that is to say of 12.2 percent of the cases of hypertension found by the epidemiological criteria, that figure decreases to 7.7% percent with clinical confirmation). With the JNC criteria, it is 14.5 percent (from 34.1 percent, it goes to 19.6 percent). This excess can be used to adjust numbers found in epidemiological studies to their real values.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8008952 TI - [Primary antiphospholipid syndrome. Clinical course features of 24 cases]. AB - OBJECTIVES: Describe the clinico-evolutionary characteristics of cases of primary antiphospholipid syndrome (PAPLS) diagnosed at our center. PATIENTS AND METHODS: Retrospective study of all patients with circulating anticoagulant type lupus (AL) (62 patients) and/or anticardiolipin antibodies (ACLA) found in our center since 1981 and 1988, respectively. TTPA, Kaolin's test (KT), and Russel's viper venom time (RVVT) and ACLA type IgG and IgM by ELISA: Only those patients meeting the criteria for PAPLS are included. RESULTS: Twenty-four patients were diagnosed with PAPLS: Eleven patients were from the enlarged TTPA group, 11 of the total with positive ACLA, and two by KT and abnormal RVVT. As for gender, 18 were women. In the past three years, 19 patients were diagnosed. The diagnostic criteria were from the very beginning: venous thrombosis in nine patients, arterial thrombosis in four, aborted repetitions in three, and plateletopenia in eight. Six patients presented pulmonary thromboembolism, the cause of death in one patient. Thrombopenia was manifested in the evolutionary course of 14 patients, only one of which being severe. Two patients have died (one of them from neoplasia), and two others have had antiphospholipid antibodies become negative. Seven patients remain without treatment, the others undergoing anti aggregating or anti-coagulant treatment. CONCLUSIONS: Plateletopenia, alone or accompanied by other symptoms, is the most common alteration of PAPLS in our area, followed by venous thrombosis which caused death by pulmonary thromboembolism in one patient. Arterial thrombotic events and aborted repetitions are by no means infrequent. PMID- 8008953 TI - [Droxicam-induced hepatitis. Description of 3 new cases and review of the literature]. AB - Three new cases of cholestatic hepatitis caused by droxicam are described, along with a revision of the other eight cases published to date. Itching, asthenia, and jaundice were the most common symptoms. Average age was 62.8 years (range: 45 82 years), and the median time of exposition was 22.7 days (range: 5-50 days). Biochemistry of the liver showed primarily cholestasis and in 4/11 cases hypereosinophilia. Two patients presented elevated levels of cholesterol and triglycerides which disappeared within the month. Clinical manifestations persisted in one patient for eight weeks after the cessation of treatment. The three patients presented in the present series presented alteration in the biochemistry of the liver two months after initiation. Liver biopsy in three patients showed centrozonal cholestasis associated with portal inflammatory activity and presence of granulomas consistent with toxic hepatitis. PMID- 8008955 TI - [Teaching Medicine: yesterday, today, and tomorrow]. PMID- 8008954 TI - [Extrahepatic portal vein aneurysm and recurrent cholestasis]. AB - Aneurysm of the portal vein is quite infrequent and its clinical manifestations is variable. The association between aneurysm of the extrahepatic portal vein and recurring obstructive jaundice has only been described on one occasion, one where there was also portal hypertension. One case of aneurysm of extrahepatic portal vein associated with recurring cholestasis is described. The diagnosis was performed via echography and abdominal TAC and confirmed by portal venography. There was no evidence of hepatopathy or portal hypertension. Possibly, the displacement of the biliary tract the portal vein is a contributing factor to recurring cholestasis in the present case. PMID- 8008956 TI - [A 31-year-old female with fever, arthritis, and heart conduction disorder]. PMID- 8008957 TI - [Current treatment of Parkinson disease]. PMID- 8008958 TI - [False-positive result of fine-needle puncture-aspiration]. PMID- 8008959 TI - [Mass localized in the axilla]. PMID- 8008960 TI - [Peritoneal pseudomyxoma secondary to mucinous cystadenoma of perforated appendix]. PMID- 8008961 TI - [Toxic megacolon caused by loperamide as initial form of Crohn disease]. PMID- 8008962 TI - [Hemoptysis, a rare complication of punction-catheterization of the subclavian vein]. PMID- 8008963 TI - [Significance of an undetermined RIBA-2 result in the confirmation of anti-HCV positivity]. PMID- 8008964 TI - [Fosfosal-induced hepatitis]. PMID- 8008965 TI - CD23 and IgE expression during the human immune response to cutaneous leishmaniasis: possible role in monocyte activation. AB - Leishmania brasiliensis causes cutaneous leishmaniasis (CL) in humans. During this infection, a variety of inflammatory mediators are produced by T cells and monocytes/macrophages. In the present study, we analysed serum IgE levels and their correlation with in situ expression of the low affinity receptor for IgE (Fc epsilon RII/CD23) in patients infected with L. brasiliensis before and following therapy. These analyses were compared to in situ expression of tumour necrosis factor-alpha (TNF alpha), interleukin 3 (IL3), interferon-gamma (IFN gamma) and IL4. Disease-free individuals from the same endemic area sensitized with L. brasiliensis antigens were also included in this work. Our data indicate that during infection, serum levels of IgE and TNF alpha increased and correlated with elevated in situ expression of CD23, IL4 and TNF alpha mRNA. This expression disappeared following successful treatment, but persisted in patients resistant to anti-leishmania therapy. Patients resistant to therapy differed from other cases by a dramatic decrease in their in vivo expression of IFN gamma protein. Analysis of CD23 function in purified human monocytes indicated that this antigen mediates IgE/anti-IgE-dependent TNF alpha production. These data suggest a possible in vivo role of CD23 in acute immune responses in human CL. PMID- 8008966 TI - Twenty years of antibody structure. PMID- 8008967 TI - Recognition of carbohydrates by antibodies. PMID- 8008968 TI - Cross-reactivity in antibody-antigen interactions. PMID- 8008970 TI - Structural aspects of conformational changes in ligand binding by antibody fragments. PMID- 8008971 TI - Structural implications of VH sequence patterns. PMID- 8008969 TI - Structural significance of sequence variability in antibody complementarity determining regions. PMID- 8008972 TI - The energetics of antigen-antibody binding. PMID- 8008973 TI - Structure of anti-peptide antibody complexes. PMID- 8008974 TI - Structure activity relationships of peroxynitrite scavengers an approach to nitric oxide neurotoxicity. AB - Nitric oxide (NO) is made by NO synthase during the conversion of arginine to citrulline. Researchers have found that they can block the actions of excitotoxins by inhibiting NO synthase. Released from excitable cells during trauma, NO may react with superoxide to form peroxynitrite. Once formed, peroxynitrite and its products can then react with proteins, lipids and nucleic acids resulting in cell injury and death. The present study was undertaken to investigate analogs of cysteine as scavengers of peroxynitrite. Peroxynitrite scavengers were assayed by Attoflo, an automated radioimmunoassay. Briefly, peroxynitrite, in a dose-dependent manner (0.1 to 10 mM), inhibited the binding of I125 cAMP to a polyclonal antibody used in the assay of cAMP. Drugs were tested for blockade of the inhibition (90%) caused by peroxynitrite at 10 mM. Cysteine blocked the inhibition of ligand/antibody binding in a dose-dependent manner (EC50 = 3 mM). Cysteine, cysteine esters, penicillamine, penicillamine esters and cysteamine were the most effective peroxynitrite scavengers. Analogs of cysteine may thereby protect cells from nitric oxide toxicity. PMID- 8008975 TI - Inhibitor effects of diltiazem, nicardipine, nifedipine and verapamil on the norepinephrine-induced contractions of the canine saphenous vein in calcium-free medium. AB - Contractile responses to norepinephrine (noradrenaline, NE 10(-5) M) in the canine saphenous vein (SV) are significantly, although slightly, reduced (14%) when induced in a physiological medium depleted of calcium for 1 hour (+ EGTA). In contrast, they are inhibited by about 75% after 24 hr in calcium free physiological saline solution (P.S.S.). ED50 of norepinephrine in 1-hr calcium free medium and in normal Ca++ P.S.S. are 6 x 10(-7)M and 4.2 x 10(-7)M, respectively. Two blockers of extracellular calcium entry have also been cited as inhibitors of intracellular calcium pool refilling. At concentrations of 10(-6)M, 10(-5)M and 10(-4)M, diltiazem and nicardipine inhibit the norepinephrine-induced contractions (NIC) in a concentration-dependent manner. At 10(-4)M, the two calcium blockers inhibit the NIC by 70% and by 72% respectively in Ca++ free (+ EGTA) P.S.S. Nifedipine and verapamil only begin to significantly inhibit NIC in Ca++ free (+ EGTA) P.S.S. at concentrations equal to or greater than 10(-5)M. At 10(-4)M concentration, control inhibition in Ca++ free P.S.S. was observed as 60% and 49%, respectively. Contrary to the other 3 calcium antagonists tested, diltiazem antagonises NIC significantly less in calcium-containing medium (45%) than in calcium-free medium (72%). Procaine at a concentration of 10(-3)M, described as sufficient to totally inhibit calcium release from its intracellular storage sites, only inhibits NIC by 52% in calcium free (+ EGTA) P.S.S. These results are consistent with the following conclusion: i) in the canine saphenous vein (SV), NIC is mainly mediated by calcium mobilization from its intracellular storage sites; ii) the calcium antagonists tested here and procaine are unable to totally inhibit, even at high concentrations, the contractions induced via intracellular calcium release; this characteristic is nonsignificant for nifedipine and verapamil at low concentrations (10(-6)M). iii) verapamil and nifedipine, like diltiazem and nicardipine at high concentrations, may not only possess the characteristics of extracellular calcium entry blockers, but also that of partial antagonist of NIC via non specific mechanisms; iv) diltiazem may relax the vascular smooth muscle of SV, not only by the above two properties, but also through another mechanism yet unknown; v) partial persistence of NIC on the SV under conditions of short or long extracellular calcium depletion may be due to a mechanism of intracellular Ca++ recycling, the smooth muscle cell partially retaining its intracellular Ca++. PMID- 8008977 TI - The influence of dietary fat on hepatic bioactivation of aflatoxin B1 in rats. AB - Fischer 344 rats were fed a low-fat high carbohydrate (HC) diet, an isocaloric fat-containing (IC) diet, a hypercaloric fat-containing (HF) diet or a commercial rodent chow. The effects of these diets were studied on the binding of aflatoxin B (AFB1) to exogenous DNA, and on the activities of hepatic glutathione transferases (GSTs), cytochromes 2B1 and 1A1. Microsome-mediated binding of [3H]AFB1 to exogenous DNA was significantly lower in the HC-rats than in the chow and IC-fed rats. No significant differences were noted between HF and either HC or IC rats. There was no significant difference in hepatic GST activity of rats fed the different diets. Our results suggest that high-carbohydrate low-fat diets reduce microsome mediated epoxidation of AFB1 to a larger extent than high-fat diets. In general, high fat diets increased cytochrome 1A1 and 2B1 activities relative to chow and high carbohydrate diet. This suggests greater detoxification of AFB1, thus reducing the amount of AFB1 available for hepatic macromolecular binding. PMID- 8008976 TI - Characterization of and the influence of calcium channel blockers on the renal excretion of pyrimidine anticancer agents. AB - The renal handling of two anticancer (a-Ca) pyrimidines 5-fluorodeoxyuridine (FUdR) and 5-fluorouracil (5-FU) was investigated in clearance experiments in CF 1 mice using specific inhibitors of classical renal transport systems. The 5-FU was derived from the metabolism of FUdR. Based on the FUdR:inulin clearance ratio and 5-FU:inulin clearance ratio, it was determined that FUdR was secreted into renal tubules while 5-FU underwent reabsorption. The secretion of FUdR was inhibited by cimetidine and dipyridamole but not by probenecid or phloridzin. While the clearance ratio of 5-FU:inulin was significantly reduced by phloridzin, it (i.e., the ratio) was not affected by cimetidine, dipyridamole, or probenecid. The impact of two calcium channel blockers, diltiazem (DZM) and verapamil (VER), on the renal handling of FUdR and 5-FU was also examined. VER increased the secretion of FUdR without affecting the reabsorption of 5-FU while DZM slightly decreased the secretion of FUdR and prevented the reabsorption of 5-FU. These data suggest that the organic cation carrier and a dipyridamole-sensitive nucleoside transporter are involved in the renal excretion of FUdR; that the renal transport of both FUdR and 5-FU is associated with the calcium channel; and that 5-FU utilizes, at least in part, the glucose transporter for its reabsorption. PMID- 8008978 TI - Platelet-activating factor (PAF) acetylhydrolase activity, type II phospholipase A2, and cytokine levels in patients with sepsis. AB - Platelet activating factor acetylhydrolase (PAF-AH) activity was measured in patients with sepsis, and its relationships with various cytokines and endotoxin were evaluated. PAF-AH activity was significantly higher (p = 0.0136) in 17 patients who died than 13 patients who survived. PAF-AH activity showed significant correlations with the plasma endotoxin, TNF-alpha, and IL-8 levels. These findings suggest that PAF-AH activity reflects the severity of the pathological condition. PMID- 8008979 TI - Relationship between thromboxane B2 and 6-keto-prostaglandin F1 alpha in sepsis. AB - To examine the roles of thromboxane A2 and prostaglandin I2, which are arachidonic acid metabolites found in patients with sepsis, we measured the serum levels of their respective stable metabolites, thromboxane B2 (TXB2) and 6-keto prostaglandin F1 alpha (6-keto-PGF1 alpha) in 22 patients with sepsis. Results were analyzed in relation to patients' survival. The levels of both TXB2 and 6 keto-PGF1 alpha were significantly higher in patients who died than in those who survived, thus reflecting the severity of the patients' illness. There was a significant correlation between the levels of TXB2 and 6-keto-PGF1 alpha. These findings suggest that TXA2 and PGI2 are chemical mediators involved in the severity of clinical sepsis. PMID- 8008980 TI - Serum and urinary neopterin levels in patients with chronic active hepatitis B treated with interferon. AB - Serum and urinary neopterin levels and serum 2',5'-oligoadenylate synthetase and DNA polymerase activities were measured in 14 patients with HBeAg-positive chronic hepatitis B treated with interferon. Treatment with interferon brought about a threefold increase over basal levels in serum and urinary neopterin levels one week after the start of treatment. Both neopterin levels remained significantly elevated during treatment but rapidly returned to basal levels after the completion of treatment. Serum and urinary neopterin levels changed with a pattern similar to that of serum 2',5'-oligoadenylate synthetase activity and with a mirror image to serum DNA polymerase activity. It is indicated that measurement of serum and urinary neopterin can be used as a marker for cell mediated immunity during interferon therapy for chronic hepatitis B, but can not be used to predict the short-term clinical effects of interferon treatment as in the case of serum 2',5'-oligoadenylate synthetase. PMID- 8008981 TI - Size-regulation and biochemical activities of the multicellular spheroid composed of rat liver cells. AB - It was reported that cell-sheets composed of rat liver cells could be obtained by using a collagen-conjugated thermo-responsive polymer, poly-N-isopropyl acrylamide, as a cell substratum and they were then able to transform into multicellular spheroids in the hydrophobic dish. In this study, we succeeded in easily obtaining the cell-sheets with the intended size by using the etched substratum. Biochemical analyses of spheroids derived from cell-sheets with areas of 0.2, 0.5 and 2.5 cm2 were carried out. Each cell-sheet rapidly aggregated at the same rate and finally turned into a multicellular spheroid within 5 days after the detachment. However, both decreases of DNA and LDH contents in cell sheets with an area of 2.5 cm2 within 24 hr after the detachment were more obvious than in the others, respectively. It is tempting to speculate from these data that the vital spheroids with the desired size can be easily obtained by using our new method. PMID- 8008982 TI - Developmental toxicity of cyclohexanediaminetetraacetic acid (CDTA) in mice. AB - Cyclohexanediaminetetraacetic acid (CDTA), an effective antagonist for the treatment of zinc, lead, and manganese poisoning was evaluated for maternal and developmental toxicity in pregnant Swiss mice. CDTA was given intraperitoneally on gestation days 6-15 at doses of 0, 270, 540, and 1080 mg/kg/day. On gestational day 18, the fetuses were examined for external, visceral, and skeletal malformations and variations. Treatment with CDTA at 1080 mg/kg/day resulted in a high level of maternal deaths, as well as less severe clinical signs (significant reduction in weight gain and food consumption). Increased resorptions, fetal deaths, and decreased number of live fetuses per litter were observed at 1080 mg/kg/day. Mean fetal body weights were also significantly decreased in this group. At 1080 mg/kg/day, CDTA caused external malformations, while the development of skeletal tissues was less affected. The no observable adverse effect level (NOAEL) for maternal and developmental toxicity of CDTA in mice was 540 mg/kg/day. Analyses of maternal and fetal tissues revealed only slight effects of CDTA on concentrations of calcium, magnesium, zinc, copper and iron. According to these results, the alterations in mineral metabolism should not be the major reason for CDTA-induced developmental toxicity. PMID- 8008983 TI - Effect of repeated injection of somatomedin C on drug metabolizing enzyme activities in rats. AB - The effect of somatomedin C on the hepatic drug-metabolizing enzyme system in rat liver after sc injection, a clinically applicable dosing route, was studied. Although liver weight was slightly increased after somatomedin C (1 mg/kg) was injected for 7 days, no significant changes were observed in other dosing group (0.1 and 10 mg/kg). There were no significant effects of somatomedin C on cytochrome P-450 and b5 contents, and NADPH-cytochrome c reductase, aminopyrine demethylase, aniline hydroxylase, and ethoxyresorufin deethylase. Additionally, somatomedin C treatment did not affect the activities of 2 alpha-, 2 beta-, 6 beta- and 16 alpha-hydroxytestosterone and androstenedione formation from testosterone. Changes relation to dosing period were also examined with 1 mg/kg of somatomedin C. In this case, hepatic levels of cytochrome P-450 and b5, NADPH cytochrome c reductase and drug oxidations did not differ significantly among groups treated for 3, 7, or 14 days. These results suggest that somatomedin C has no effect on the hepatic mixed-function oxidase system. PMID- 8008984 TI - Role of hepatic copper-metallothionein on liver function of Long-Evans cinnamon rats with a new mutation causing hereditary hepatitis. AB - Liver slices from Wistar and Long-Evans Cinnamon (LEC) rats were incubated while open to the atmosphere to assess the liver function in LEC rats. Leakages of glutamic-oxaloacetic transaminase (GOT) and lactic dehydrogenase (LDH) into the medium were significantly lower in the LEC rat than in the Wistar rat. Furthermore, no pronounced enhancement of the concentration of thiobarbituric acid-reactive substances (TBARS) was found in the LEC rat. Hepatic Cu and Cu metallothionein (Cu-MT) concentrations were 355.0 +/- 18.7 micrograms/g liver and 2559 +/- 181 micrograms/g protein in the LEC rats, whereas Wistar rats showed 4.1 +/- 0.1 Cu microgram/g liver accompanied by 16 +/- 4 micrograms/g protein of MT. The decrease of intrahepatic Cu-MT in LEC rats was stimulated by incubation with Fenitrilotriacetate (Fe-NTA). There was a direct correlation between the enhancement of TBARS and disappearance of Cu-MT. Our results suggest that hepatic Cu-MT in LEC rats protects against liver injury stimulated by oxidative stress. PMID- 8008985 TI - Pharmacokinetics and toxicity of inhaled human natural interferon-beta in patients with lung cancer. AB - Eight patients with a thoracic malignancy inhaled single doses of 3-100 x 10(6) IU of human natural interferon (IFN)-beta via a dosimeter-equipped jet nebulizer. After inhalation IFN-beta was not detectable in any of the serum samples as measured using an antiviral bioassay. Except for a slight body temperature rise and an 18% decrease in peak expiratory flow rate observed in 1 patient the patients did not experience any major side effects. Inhaled natural IFN-beta in this study was tolerated better than inhaled IFN-alpha or IFN-gamma in our previous studies. IFN-beta might thus be a promising local treatment for pulmonary diseases. Further work is needed to investigate the concentrations of biologically active IFN in alveolar epithelial lining fluid after inhalation and the therapeutic effect of inhaled IFN-beta. PMID- 8008988 TI - Combined portal and pulmonary hypertension in sarcoidosis. AB - A case is reported of a 48-year-old man previously diagnosed as having mitral valvular disease, who was admitted for evaluation of chronic cor pulmonale. Seven years before admission, an intraoperative liver biopsy had shown multiple noncaseating granulomas. The further course was characterized by progressive chronic intrahepatic cholestasis and portal hypertension. Right heart catheterization revealed a mean pulmonary artery pressure of 43 mm Hg and a normal wedge pressure (5 mm Hg). A perfusion lung scan was normal. Open lung biopsy demonstrated noncaseating granulomas and extensive pulmonary fibrosis. To our knowledge, only one case of sarcoidosis with combined portal and pulmonary hypertension has previously been described. PMID- 8008987 TI - Carcinosarcoma of the lung. Report of a case and review of the literature. AB - We describe a case of carcinosarcoma of the lung in a 60-year-old female who was admitted with complaints of productive cough and an abnormal shadow in the chest X-ray. Sputum cytology showed both squamous cell carcinoma and adenocarcinoma cells. Malignant nonepithelial cells were identified in the needle biopsy specimen. Right middle and lower lobectomy was performed to reveal a carcinosarcoma by microscopic and immunohistochemical examination. This case was histologically unusual because it presented multiple carcinomatous elements (squamous cell carcinoma and adenocarcinoma). It was classified as peripheral type according to the clinical classification, showing an extremely poor prognosis. The histogenesis and clinical features of this rare tumor are discussed. PMID- 8008986 TI - Hemopneumothorax secondary to multiple cavitary metastasis in angiosarcoma of the scalp. AB - We report a case of hemopneumothorax secondary to multiple cavitary metastasis in the angiosarcoma of the scalp in an 86-year-old woman, who died of respiratory failure. At autopsy, multiple cavities were found in both lungs. Histologic specimen of the cavitary metastasis of the lung showed that tumor cells proliferated forming several tubular spaces and these tubular spaces seemed to communicate with the central cyst. These findings suggested that imperfect vessel like structures of the cavitary metastasis are likely to break down and finally grow up to large thin-walled cavities. PMID- 8008989 TI - Review of respiratory care of the patient with amyotrophic lateral sclerosis. AB - Respiratory failure is the leading cause of death in patients with amyotrophic lateral sclerosis (ALS). We review the physiology of respiratory compromise in ALS and techniques of monitoring respiratory function. Treatment options, including pharmacologic interventions, aspiration precautions, and invasive and noninvasive modes of mechanical ventilation are reviewed. Our clinical experience with respiratory failure in ALS demonstrates significantly prolonged survival in subjects who elect to receive noninvasive mechanical ventilation (19.25 vs. 80.4 days, p < 0.01). Four of 18 patients who elected to receive noninvasive ventilation decided to discontinue treatment. Four of 13 patients who were receiving mechanical ventilation elected to discontinue life support. The decision to utilize these modalities must be made with realistic considerations of the patient's quality of life. PMID- 8008990 TI - Changes in regional ventilation during histamine bronchial challenge in stable asthma. AB - Our objective was to examine the changes in regional ventilation during histamine induced bronchoconstriction in stable asthma. We measured regional ventilation by a new method which measures regional distribution of inhaled 127Xe during tidal breathing by a gated method and, by simultaneously measuring 99mTc counts from labelled macroaggregates, allowed for changes in lung shape during the breathing cycle. We studied 10 asthmatic patients [forced expiratory volume in 1 s (FEV1 2.04-4.37 litres)] and measured, in addition to the regional ventilation, oxygen saturation (SaO2), minute ventilation (VE) and tidal volume (Vt) before and after inhaling enough histamine to lower FEV1 by > 20% and/or SaO2 by > 4%. Histamine inhalation reduced FEV1 by 0.44-1.15 liters and SaO2 by 0-4%. It increased VE and functional residual capacity (FRC) in 8 of the 10 patients. The FEV1 fall did not correlate with the SaO2 fall, VE or FRC changes. Histamine inhalation increased apical ventilation in most patients, but the changes in regional ventilation in the left and right lungs were asymmetrical in 17 out of the 30 lung regions studied (upper, middle and lower paired regions in 10 patients). These results demonstrate that histamine bronchial challenge causes uneven regional ventilation. Any resultant change in ventilation-perfusion balance may be the underlying mechanism of oxygen desaturation seen in this procedure and in spontaneous attacks of asthma. PMID- 8008991 TI - Bronchial reactivity to isocapnic hyperventilation: results in an unselected population of outpatients with known or suspected asthma. AB - Isocapnic hyperventilation with dry air is nearly as effective as with dry cold air, and appears to be a valuable screening test for bronchial hyperresponsiveness. However some incidental factors such as prechallenge bronchoconstriction, level of hyperventilation, age and smoking habits have barely been examined or were investigated in small samples of either normals or well-characterised asthmatics. In an inhomogeneous population of 186 outpatients with known asthma, 286 with suspected asthma and 32 normals, a single isocapnic hyperventilation challenge of 6-min duration was performed. There was a weak, but significant correlation between the degree of prechallenge airway function and the bronchial response, assessed by the change in forced expiratory volume in 1 s (r = 0.27, p = 0.000) in known asthmatics, but not in patients with suspected asthma and in normals. No significant relation was found between the level of hyperventilation and the bronchial response when comparing the bronchial response to the single-dose hyperventilation test between the subjects (NS). Increasing age appears to be associated with an attenuation of the response in known asthmatics (r = 0.21, p = 0.004), but not in patients with suspected asthma. Smoking habits did not affect the bronchial response in this study. In conclusion, the main finding is that there is a weak correlation between baseline airway obstruction and the subsequent response to isocapnic hyperventilation, a slow decline in response with age and no increase in responsiveness in smokers. Hence, isocapnic hyperventilation is a relatively robust test for assessing bronchial reactivity in an inhomogeneous population of outpatients like ours. PMID- 8008992 TI - Impairment of exercise capacity in various groups of HIV-infected patients. AB - It is known that pulmonary function is impaired during the course of HIV infection even in early stages. In order to estimate the resulting reduction of exercise capacity, different groups of HIV patients were investigated. Group 1 consisted of 20 patients without a history of respiratory disease and without actual lung disease, group 2 of 18 patients with a former episode of Pneumocystis carinii pneumonia (PCP) without actual lung disease, and group III of 37 patients with different broncho-pulmonary complications including PCP. 20 normal subjects served as controls. Spirometry, diffusing capacity (DLCO) and exercise tests including arterial blood gas analysis (BGA) were performed in patients and controls. Compared to the controls group 1 patients revealed a decreased DLCO (TCO: 83 +/- 15 vs. 67 +/- 15% pred.norm.) while spirometric data were normal. VO2 and O2 pulse at the anaerobic threshold (17.7 +/- 5.1 vs. 14.3 +/- 2.6 ml/kg.min and 10.8 +/- 4.0 vs. 8.6 +/- 1.9 ml/beat, respectively) and maximum exercise (33.9 +/- 9.7 vs. 22.1 +/- 3.4 ml/kg.min and 15.0 +/- 5.0 vs. 11.3 +/- 2.5, respectively) were decreased, whereas AaDO2, VD/VT, and the HR/VO2 slope were normal. The reserves of heart rate and ventilation were high. Except for a reduced maximum work rate in group 1, no significant difference was found between groups 1 and 2. Group 3 patients differed most from groups 1 and 2 with respect to spirometry, DLCO and AaDO2, rather than VO2.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8008993 TI - Effects of the sauna on diffusing capacity, pulmonary function and cardiac output in healthy subjects. AB - The present study examined possible short-term effects of the heat stress during sauna bathing on gas exchange, especially in correlation with changes in cardiac output. The results obtained are as follows: (1) The heat stress of sauna bathing caused a slight but not significant increase in diffusion capacity (p = 0.239) and no change in other pulmonary function parameters. (2) Cardiac output and cardiac index increased slightly but not significantly (p = 0.2455 and p = 0.2719). We conclude that heat stress in sauna neither influences gas exchange nor does it cause a significant increase in cardiac output. PMID- 8008994 TI - Ventilatory function in nonsmoking rural Indian women using different cooking fuels. AB - Lung function parameters, forced vital capacity (FVC), forced expiratory volume in 1st s (FEV1), peak expiratory flow rate (PEFR), were measured in 3,318 nonsmoking Indian women using four different types of cooking fuels (biomass, liquified petroleum gas, kerosene and mixed). Biomass fuel users had FVC values less than 75% predicted (73.42 +/- 0.90; mean +/- SE) whereas in other groups it was more than 75% of predicted, though less than 80% of the predicted values. However, FEV1, FEV1/FVC (%) and PEFR were within normal limits in all the four groups. The absolute values of all the three parameters of lung functions were the lowest in the biomass and mixed fuel users. A negative correlation was observed between these parameters and the duration of cooking and exposure index. Thus the present study showed that, lung function, particularly FVC, is affected by indoor air pollution due to domestic cooking more so with biomass fuel. Better housing and use of smokeless devices for cooking might be helpful to avoid this effect on lung. This ventilatory impairment seems to be more of the restrictive (parenchymal) type, since obstruction could be ruled out. A longitudinal study is needed to demonstrate whether or not these changes are variable, reversible or progressing to fibrosis. PMID- 8008996 TI - Effect of recombinant human adult T cell leukemia-derived factor on rat lung reperfusion injury. AB - The formation of reactive oxygen species (ROS) is a major factor responsible for reperfusion injury in lungs. Adult T cell leukemia derived factor (ADF), a polypeptide made of 104 amino acids, is induced by a variety of stresses including X-ray, ultraviolet, H2O2, and mitogen. ADF has a reducing activity, which catalyzes the proton transfer between thiol-radical of cystein-containing proteins. Furthermore, ADF has a protective activity of ROS which are formed by xanthine oxidase and other alternative pathways in vitro. Using a rat in vivo model of lung ischemia, we examined the protective effect of recombinant human ADF (rhADF) against ischemia reperfusion injury of the lung. Ischemia, lasting for 75 min, was induced in the left lung of rats at 23 degrees C. The lung was then reperfused. These animals were divided into two groups: group 1 (n = 6, treatment with normal saline) and group 2 (n = 6, treatment with 28 micrograms/g of rhADF). One minute after the beginning of reperfusion, arterial oxygen tension (PaO2) decreased significantly in both groups (p < 0.01), without any significant intergroup difference (55.5 +/- 9.8, 49.8 +/- 8.6 mm Hg, respectively). Twenty minutes after reperfusion, PaO2 was significantly higher (p < 0.05) in group 2 (113.0 +/- 8.1 mm Hg) than in group 1 (72.3 +/- 13.6 mm Hg). The wet/dry weight ratio was significantly higher in group 1 (7.31 +/- 0.54) than in group 2 (5.82 +/- 0.36). Histologically, lung injury tended to be milder in group 2 than in group 1. These results suggest that rhADF has a protective effect against ischemia reperfusion injury of the rat lung. PMID- 8008995 TI - Clinical, anamnestic and coagulation data in patients with suspected or confirmed pulmonary embolism. AB - We studied 84 consecutive patients referred with the suspicion of pulmonary embolism (PE) to investigate the influence of clinical and hematological profiles on the diagnosis and severity of this disease and recovery. Diagnosis of PE was confirmed in 48 out of 84 patients by perfusion scintigraphy and/or pulmonary arteriography. Severity of PE and entity of recovery were investigated by measuring standard PaO2 on blood gas analysis and the number of unperfused lung segments ULS on perfusion scintigraphy. Most common clinical predisposing conditions were more frequent, though not significantly so, in embolic patients and a very low prevalence of PE was appreciable in patients without clear predisposing conditions. Among coagulation factors, only thrombin-antithrombin (TAT) complexes were twice as high in embolic as in nonembolic patients (14.0 +/- 13.6 vs. 7.0 +/- 4.2 ng/ml; p < 0.02), while there was no statistically significant difference between embolic and nonembolic patients for activated partial thromboplastin time, prothrombin time, antithrombin III, protein C, fibrinogen, plasminogen, alpha 2-plasmin inhibitor, and plasminogen activator inhibitor-1. Sensitivity and specificity of TAT complexes in diagnosis of PE were 95.8% and 30.5%, respectively. Therefore, normal values of TAT complexes may help exclude the diagnosis of PE, while abnormal values allow to reinforce the clinical suspicion of PE. No relation was found between coagulation parameters and the severity of PE. The follow-up of 48 patients with confirmed PE was favorable on the average; however, neither the presence of predisposing conditions nor abnormal coagulation parameters allow to predict the degree of functional and scintigraphic improvement during follow-up. PMID- 8008997 TI - European code against cancer. A booklet for general practitioners. PMID- 8008998 TI - [Prognostic role of pregnancy on the course of HIV infection: a retrospective cohort study (1985-92)]. AB - In a hospital-based cohort study of HIV-infected patients, we compare the progression of the disease (occurrence of CDC group IV, death, decline of CD4 below 200/mm3) between 55 women with delivery and 89 matched control HIV positive women with no history of pregnancy. After a mean follow-up of three years, no significant difference was observed between the two groups even after adjustment on prognostic variables. PMID- 8008999 TI - [Risk factors of cerebral toxoplasmosis in patients with HIV infection: data of a primary prevention trial]. AB - To identify risk factors for cerebral toxoplasmosis (CT) in HIV patients (pts) with positive serology for Toxoplasma gondii and CD4 < 200/mm3, data from the placebo group (N = 280) of a primary prophylaxis trial, were analyzed. The probability of onset of CT (n = 46) was, at one year, 13.1%. Three baseline variables were independently associated with a higher risk of CT: group IV non AIDS, AIDS stage and CD4 < 50/mm3. Initial titer of antibodies to Toxoplasma gondii was not. PMID- 8009000 TI - [Primary prevention of cerebral toxoplasmosis in patients with HIV infection: results of a double-blind randomized trial, pyrimethamine versus placebo]. AB - To assess the efficacy of pyrimethamine (Pyr) for primary prophylaxis of cerebral toxoplasmosis (CT) in HIV patients (pts), 554 pts were randomized in a double blind, placebo-controlled trial (mean follow-up: 14 months). The intent-to-treat analysis found no significant difference in the incidence of ct at 1 year: 12% (Pyr) versus 13% (Pcb) nor in survival. Side-effects leading to stop the study drug were more frequent in Pyr group, especially cutaneous rashes: 8% (Pyr) versus 2% (Pcb). PMID- 8009001 TI - [Membrane fatty acids and blood antioxidants in 77 patients with HIV infection]. AB - We have measured the fatty acid (FA) composition of erythrocyte membranes and plasma anti-oxidants in HIV+ patients. Saturated FA are higher and poly unsaturated FA lower than in controls (P = 0.02). Selenium (Se) is lower in patients less than 400 CD4 cells/mm3 (P = 0.002). Vitamin A is lower in the HIV+ regardless of the CD4 cell count. Se and vitamin A are correlated to nutritional markers (body mass index and albumin). PMID- 8009002 TI - [Interferon and blood tumor necrosis factor in 95 patients with HIV infection]. AB - We have measured TNF-alpha and interferon alpha in 95 HIV positive patients and 20 healthy subjects. TNF-alpha was higher in the HIV+ patients (P = 0.0001) and was correlated to the CD4 cell count (P = 0.02) and cholesterol (negatively) (P = 0.04). Interferon-alpha was correlated to the wasting syndrome (P = 0.002), hypertriglyceridemia (P = 0.004) and haematocrit (P = 0.04). PMID- 8009004 TI - [Sicca syndrome and low-grade chronic viral hepatitis C. Apropos of a series of 50 cases]. AB - Systemic manifestations are described in chronic hepatitis C. Haddad et al have showed the prevalence of sicca syndrome with lymphocytic sialadenitis. We analysed prevalence in 50 patients suffering from chronic hepatitis C with histologic low rank. 50% of them have pronounced abnormality of lachrymal secretion without sialadenitis. It seems that sicca syndrome is present in low rank hepatitis. In that case xerophtalmia preceded xerostomia. PMID- 8009003 TI - [Identifying hepatitis C virus by the gene amplification technique in the saliva of patients for whom the search is simultaneously negative in their serum: 9 cases]. AB - RNA-PCR for Hepatitis C virus was positive in saliva sample of 9 patients, while it was negative in their serum. Clinical and biochemical results of these patients are presented. Saliva detection of HCV is useful for diagnostic of hepatitis, sicca syndrome. PMID- 8009006 TI - [Peripheral neuropathies in essential mixed cryoglobulinemia: influence of positive serology for hepatitis C virus]. AB - Among 15 patients suffering from peripheral neuropathy, 67% had anti-HCV antibodies. The anti-HCV antibodies positive patients had more severe multiple mono- and poly-neuropathies and more frequent inflammatory neuromuscular infiltrates. In some VHC positive cases, the peripheral neuropathy was efficiently treated by interferon alpha. PMID- 8009005 TI - [Western blotting analysis of cryoglobulins associated with chronic hepatitis C]. AB - In a prospective study, a monoclonal component was found in 29/89 (33%) of mixed cryoglobulinemia (MC) associated with hepatitis C virus (HCV) infection, with a IgM in 87% of cases and a Kappa/Lambda ratio at 1.8. HCV RNA anti-HCV antibodies were demonstrated in both MC with and without monoclonal component. PMID- 8009007 TI - [Autoimmune biological anomalies in 35 patients with chronic viral hepatitis C treated over 6 months with interferon and followed-up over a year]. AB - Several clinical or biological autoimmune disorders, particularly lupoid diseases, are associated with chronic hepatitis C. They may be exacerbated by alpha IFN, but they are not involved in the response to therapy. PMID- 8009008 TI - [Chronic viral hepatitis C and interferon: results after a year and predictive factors of response (a multivariate study with 35 patients)]. AB - Six months alpha IFN therapy was efficient for chronic viral hepatitis C in 31% patients after six months and in 17% after one year. Cirrhosis, low serum albumin or prealbumin levels and elevated IgA seric level were non responsiveness predictive factors. PMID- 8009009 TI - [Genetic hemochromatosis disclosed by isolated increase of aminotransferases]. AB - The authors report five cases of genetic hemochromatosis in asymptomatic patients with elevated serum aminotransferases. They precise the interest of liver biopsy and hepatic iron concentration especially of hepatic iron index. PMID- 8009010 TI - [Systemic manifestations of rheumatoid arthritis: prognostic value of the HLA DRB1 0405 allele]. AB - The aim of the present study was to determine HLA DRB1* genotype by PCR-RFLP analysis in patients with rheumatoid arthritis (N = 122) associated with extra articular manifestations (N = 24). A significant increased of DRB1* 0405 was found in RA patients with extra-cellular involvement (odd-ratio = 8.33, confidence interval = 1.44 - 56.7). In patients with RA, HLA DRB1*0405 allele might constitute a susceptibility marker of extra-articular involvement such as vasulitis or cardio-pulmonary manifestations. PMID- 8009011 TI - [Felty's syndrome: retrospective study of 12 cases]. AB - A retrospective study of twelve cases of Felty's syndrome was performed. The main points of this syndrome (clinical presentation, physiopathology, complications, treatment) are described. PMID- 8009012 TI - [Digital arthropathies: uncommon complication of Still's disease]. PMID- 8009013 TI - [Cardiac complication of adult-onset Still's disease: from pericarditis to tamponade, sometimes a manifestation of the disease]. AB - Cardiac tamponade is very seldom complication of adult onset-Still's disease. We reported 2 cases; it was the first manifestation of the disease in one case. PMID- 8009014 TI - [Is the expression of TNF-alpha and cell adhesion molecules a marker of development of rheumatoid vasculitis?]. AB - TNF-alpha, ICAM1, VCAM1, ELAM, CD44 and DR expression were studied (indirect immunoperoxydase methods) on labial salivary gland sections in 5 patients with proven rheumatoid vasculitis (before and after treatment), 5 patients with RA and 5 normal controls. TNF-alpha and cell adhesion molecules were particularly expressed in vasculitic areas of patients with systemic vasculitis and only before the onset of the treatment. PMID- 8009015 TI - [Rheumatoid purpura in adults. Retrospective study of 38 patients]. AB - The authors report retrospectively 38 cases of Schonlein-Henoch purpura (20 males, 18 females; median age, 26 years). Skin (37/38) and joint (21/38) manifestations are similar to those seen in children. Gastro intestinal (22/38) manifestations are less complicated. Long term outcome of the disease depends on kidney's involvement (32/38) and is severe: chronic renal failure in 31%. PMID- 8009016 TI - [Joint manifestations and parvovorus B19 infections: 8 cases]. AB - Human Parvovirus B19 (PB19) may cause joint manifestations. We report eight cases of polyarthritis associated with PB19 IgM: six cases of acute polyarthritis spontaneously resolving within a few days, and two other cases suggesting that PB19 should be responsible for accutisation of chronic disease (lupus with Kikuchi's disease and HLA B27 related arthritis). PMID- 8009017 TI - [Multiple arterial dissections and inflammatory syndrome: apropos of 4 cases]. AB - We report four cases of multiple arterial dissection associated with an inflammatory syndrome. The features of lesions and the absence of histological inflammatory arterial disease suggest an arterial dysplasia complicated by an infectious disease. PMID- 8009018 TI - [Anti-endothelial cell antibodies in vasculitis in general, Sneddon's syndrome in particular]. AB - Stringent conditions have been applied to set up an "enzyme-linked immunosorbent assay" to detect anti-endothelial cell autoantibodies. These predominated in Sneddon's syndrome. PMID- 8009019 TI - [Long-term prognosis of arterial lesions of Behcet's disease]. AB - We analyzed the charts of 25 patients with arterial lesion in Behcet's disease with mean follow-up 76 months. We conclude that prognosis is poor. Corticosteroids and surgery if possible is needed, anti-aggregant or anticoagulants and prosthetic rather than venous graft are suitable. This therapy does not exclude the risk of relapse. Immunosuppressive drugs in addition to corticosteroids seem to be more efficient than corticosteroids alone but the therapeutic modalities need to be define. PMID- 8009020 TI - [Role of the titration of anti-neutrophil cytoplasmic antibodies in therapeutic follow-up of patients with systemic vasculitis]. AB - We studied clinical and biological data of 18 patients presenting ANCA associated diseases for 16 months at least. Five relapses were preceded by ANCA elevation, 1 relapse was not. Four transient elevations were noted without any clinical event. We think ANCA level elevation by itself is not enough for deciding therapy intensification, clinical data are necessary for doing so. PMID- 8009021 TI - [Is the risk of pneumocystosis predictable in Wegener's disease?]. AB - Twelve cases of Pneumocystis pneumonia in patients with Wegener's granulomatosis were compared with a control-group of 32 patients. Our study showed that the dose of cyclophosphamide received in the first three months and a profound lymphocytopenia were strongly predictive of a risk of Pneumocystis carinii pneumonia in these patients. PMID- 8009022 TI - [Prevalence of antiphospholipid antibodies in systemic diseases and thrombotic pathologies: apropos of a series of 135 searches of phospholipid antibodies realized for a prospective follow-up]. PMID- 8009023 TI - [Positive predictive value of thrombotic complication from the assay of anticardiolipin antibodies. Apropos of systematic assays in 111 patients]. PMID- 8009024 TI - [Phlebitis of the upper limbs: causes and current treatments. Apropos of 17 cases]. AB - A review of 17 consecutive patients in whom deep venous thrombosis of the upper extremity had developed was conducted. The major causes identified were related to thoracic outlet syndrome and venous catheterization. Venogram was necessary for the diagnosis in two patients. No pulmonary embolization occurred. Thirteen patients were treated by low-molecular-weight-heparin complication. PMID- 8009025 TI - [Treatment of venous thromboembolic disease in patients with cancer]. AB - Results of classical anticoagulant therapy in cancer patients with venous thromboembolism (VT) are highly discussed. We retrospectively analysed the outcome of 43 patients with VT and cancer: 32% developed specific complications during either i.v. heparin therapy (10 +/- 0.9 days) or treatment by antivitamin K (106 +/- 14.9 days). Recurrence of thromboembolism (16%) and/or hemorrhages (16%) were much more frequent than in patients without cancer, underlying need for alternative therapy in cancer patients with VT. PMID- 8009026 TI - [Clinical aspects of infectious endocarditis in internal medicine. Apropos of 40 cases]. AB - We report a series of 40 cases of infectious endocarditis, diagnosed on a 10-year period in a department of Internal Medicine. Initial clinical features were not suggestive of endocarditis and led to delayed hospitalization and diagnosis. PMID- 8009027 TI - [Is the immunologic evaluation in endocarditis of value?]. AB - Forty-seven patients were included in a prospective trial to define the interest for searching immunologic abnormalities during endocarditis. No specific abnormalities were found, aside some patients with endocarditis who have a high levels of immune complexes. These results suggest that the interesting immunologic abnormality is the presence of an high level of immune complexes could be of interest in endocarditis. PMID- 8009028 TI - [Value and limitations of the endomyocardial biopsy in HIV infection]. AB - The authors evaluated the interest of endomyocardial biopsy in 19 consecutively hospitalized patients with AIDS. Histopathological study dit not exhibit opportunistic infection but showed aspecific myocarditis in nine patients. PMID- 8009029 TI - [Peripartum dilated cardiomyopathy. A model of multifactor disease?]. AB - The peripartum cardiomyopathy is a rare condition in Europe but a very frequent disease in Sahelian Africa. The risk factors are: heat, hard physical exertion during pregnancy, hypertension, sodium diet, ablutions with hot water during the postpartum period, selenium deficiency and probably latent myocarditis (viral?) PMID- 8009030 TI - [Prevalence of arterial hypertension in the Brittany population]. AB - The epidemiology of arterial hypertension was studied from 1988 to 1991 in a region in the west of France comprising 500,000 inhabitants. Prevalence of arterial hypertension was calculated to 16.2%, significantly higher in men than in women (22.5% vs 11.2%). PMID- 8009031 TI - [The diabetic foot: prognosis in a series of 75 patients]. AB - Prognosis for 75 diabetic patients with foot ulcers. The aim of the study was to evaluate the prognosis regarding amputation and mortality in 75 consecutively presenting diabetic patients admitted because of foot ulcers. Median follow-up was 16 months. The amputation rate was 69% but only 4 major amputations were done. The mortality rate was 10.6%. Peripheral vascular disease was present in 69 patients. These finding stress the poor short-term prognosis of diabetic patients with foot ulcers and peripheral vascular disease. PMID- 8009032 TI - [Hepatic polycystic disease is not always associated with polycystic kidney: epidemiological data]. AB - Adult polycystic disease of the liver (APLD) and of the kidney (ADPKD) is considered to represent one entity. In 75 ADPKD kindreds with 259 affected members, ultrasonography and/or CT were performed in 186 (71.8%) from 64 kindreds (85.3%). We demonstrated that ADPKD with or without APLD are two separate phenotypes and suggest genetic heterogeneity of these two entities. PMID- 8009033 TI - [Internal medicine DES 10 years after creation. Results of the survey realized by the Association of young internists]. AB - The internal medicine young practitioners association (AJI) did set, during 93 spring, a survey among the registered internal medicine interns since 1984, regarding their training and future. 88 did answer, showing a certain homegeneous training but a deep care in their future. Most would wish a dual activity in general hospitals : internal medicine and an other speciality acquired during their training. PMID- 8009034 TI - [Pathology of leisure activities: sliding sports, jogging, rugby, golf, tennis]. PMID- 8009035 TI - [Methods of evaluation of left ventricular dysfunction]. PMID- 8009036 TI - [Focus on cardiac transplantation within the framework of cardiomyopathies]. PMID- 8009037 TI - [Cardiac sarcoidosis: apropos of 27 cases]. PMID- 8009038 TI - [Mechanisms of cardiac involvement in systemic scleroderma, apropos of 3 cases]. AB - We studied myocardial manifestations of systemic sclerosis in three patients. Two patients were symptomatic. A transthoracic echocardiography, a coronary angiography, a cardiac catheterization, thallium scans with dipyridamol completed by thoracic cold exposure and endomyocardial biopsy with immunohistological study were performed. None of them have coronary stenosis. In the three cases abnormalities of myocardial perfusion were detected, two of them have fibrosis. The immunohistological study always showed an anusual expression of HLA DR on cardiac fibroblasts. PMID- 8009039 TI - [Cardiac involvements in scleroderma: study with echocardiography and cardiac Doppler in 38 patients]. AB - A study of heart lesions has been conducted in 38 patients with systemic sclerosis using echocardiography, doppler and colour doppler. Abnormalities were found in 66% patients. Valvulopathies (mainly mitral regurgitation) were the most frequent lesions (45%). The presence of anti-SCL70 antibody was correlated to right cavities dilatation. Pulmonary hypertension was found in 6 patients. PMID- 8009040 TI - [Changes in the diastolic left ventricular function in primary antiphospholipid antibody syndrome]. AB - Previous studies have shown that left ventricular (LV) diastolic function is frequently impaired in patients with systemic lupus erythematosus. We prospectively studied echo-Doppler indices of LV diastolic function in 18 patients with primary antiphospholipid syndrome (PAPS), who where compared to a group of 18 healthy controls. Heretofore undescribed LV relaxation abnormalities were found in the PAPS group: this finding suggests the existence of a causal link. PMID- 8009041 TI - [Evaluation of hypertrophic cardiomyopathy in treated essential hypertensive patients]. AB - Assessment of left ventricular hypertrophy (LVH) in 231 essential hypertensive patients (61 year'old) treated in a department of internal medicine. Incidence of LVH defined by echocardiography: 34%. Better relationship between LVH and ambulatory blood pressure (BP) monitoring than with casual BP. Influence of age and obesity in the occurrence of LVH. PMID- 8009043 TI - [Alcohol consumption and primary dilated cardiomyopathy. Comparison with a population of patients with coronary disease]. AB - Alcohol consumption was compared between 23 men admitted to hospital with idiopathic dilated myocardiopathy (DCM) and 46 men with coronary artery disease. Duration of regular daily alcohol, heavy daily alcohol, mean daily alcohol consumption, in particular consumption of wine were higher in patients with DCM. Among the biological markers, only serum levels of immunoglobulin A and bilirubin were increased in pts with DCM. PMID- 8009042 TI - [Can the assay of angiotensin converting enzyme be a marker of observance in cardiology practice?]. PMID- 8009044 TI - [Dilated cardiomyopathies in severe cardiac failure in chronic alcoholics: clinical course after complete withdrawal]. AB - We have prospectively evaluated 6 patients admitted for a severe heart failure in alcoholic patients with dilated cardiomyopathy. We concluded that complete abstinence results in a short-term clinical improvement, associated to a significant increase in left ejection fraction. PMID- 8009045 TI - [An epidemiological survey on iatrogenic disease in hospitals]. AB - In a "on a given day" study, we analysed the prevalence and causes of drug related and non-drug, related iatrogenic illnesses. The human and financial costs of iatrogenic illnesses show that risk-prevention measures are required. PMID- 8009046 TI - [Primum non nocere, a forgotten adage at times. Apropos of 106 cases of iatrogenic pathologies collected in a year]. AB - Results of a prospective trial showed that 7.9% of patients in an internal medicine department were affected by a drug-induced pathology (DIP). Reasons for this include non respect of contra-indications or to non supervision of treatment such as anti-hypertensive drugs. DIP affected more often elderly patients, and reflected superconsummation of medication. PMID- 8009047 TI - [Prospective study of the prescription of non-steroidal anti-inflammatory agents in a reception medical service of a university hospital. Influence of the prescriptor]. AB - Non-steroidal anti-inflammatory drugs (NSAIDs) are estimated to be excessively prescribed. We have prospectively collected all drug prescriptions written by 50 doctors in an Outpatient Service, during a 5-day period. The purpose of this study was to draw the outline of NSAID prescriptors. Junior doctors (66%) wrote more controversial NSAID prescriptions (66%) than other doctors. PMID- 8009048 TI - [Drugs and brief losses of consciousness in the elderly. Results of a case control multicenter study]. AB - To study the possible role of drugs intake in syncope in elderly patients, we conducted a multicentric case-control study in 588 cases and 1818 controls, controlling as an essential confounding variable the underlying cardiovascular diseases. The following class were in excess among the case: non tricyclic antidepressants (p < 0.0001, RR: 4.5), neuroleptic drugs (p < 0.05, RR: 1.8), and antiparkinsonian drugs (p < 0.02, RR: 2.7). PMID- 8009049 TI - [A new cause of unexplained prolonged fever: estroprogestogen treatments, apropos of 12 cases]. AB - Twelve female patients treated by progestogens with or without estrogens presented with prolonged (1 to 48 months) elevation of body temperature above 37 degrees C but below 38 degrees C. They had usually continued taking their temperature after and initial transitory febrile episode. Most had had multiple diagnostic tests which remained negative. Temperature became normal after cessation of hormonal treatment. PMID- 8009050 TI - [Cardiac complications of halofantrine: continuous electrocardiographic study (holter) in 20 patients]. AB - Three cases of long QT-interval due to halofantrine were documented in 1992 in France. Two of them had a congenital long QT-interval (Romano-Ward syndrome). We performed a prospective study of cardiac monitoring in 20 patients taking halofantrine. Minimal ECG changes were noted with lengthening of the QT-interval. Systematic ECG is necessary before giving halofantrine. PMID- 8009051 TI - [Thyroid dysfunctions related to amiodarone. Prospective survey with 116 patients]. AB - Thyroid hormones, TSH and antithyroid antibodies were prospectively controlled in 116 patients treated with amiodarone. Hypothyroidism occurred in 4 patients (3.7%) mainly early (average = 6 months). Hyperthyroidism was seen among 13 patients (11.9%) and its prevalence was proportional to therapy duration. PMID- 8009052 TI - [Datura: an easily accessible hallucinogen, a poisoning to be evoked. Apropos of 10 cases]. AB - A retrospective study of ten cases of intoxication due to Datura were reported. Clinical symptoms were those of atropinic intoxication, associated with hallucinations and aggressiveness. The diagnostic is supported by clinical examination. Laboratory examinations are useful only for differential diagnosis. PMID- 8009054 TI - [Bone marrow necrosis in malignant hemopathies. 7 cases]. AB - The authors report 7 cases of bone marrow necrosis during hematological malignant diseases:3 leukemia, 4 lymphoid malignancies. The main clinical features were bone pain and fever. The bone marrow aspiration and/or biopsy allow diagnosis. The prognosis was in all cases very poor. PMID- 8009053 TI - [Central anemia sensitive to intravenous immunoglobulins]. PMID- 8009055 TI - [Hodgkin's disease and HIV infection. Study of 40 cases]. AB - Hodgkin's disease seems to be more frequent in HIV infected patients than in general population with peculiar clinical and pathological aspects. We describe 40 cases of Hodgkin's disease in HIV infected patients followed between 1983 and 1993. PMID- 8009056 TI - [Correlation between the serum level of soluble CD16 and the staging of myeloma: study of 214 serums]. AB - Soluble CD16 (sCD16) are soluble part of Fc receptor for IgG which control in mice, proliferation of hybridoma B cells and IgG production. The levels of sCD16 in 165 myeloma patients and 29 patients with MGUS appear significantly different:25a.u./ml versus 144a.u./ml and values of stage I are significantly higher than those of stages II + III.sCD16 might be a prognosis factor in myeloma. PMID- 8009057 TI - [Enterovirus infections and systemic clinical manifestations with prolonged inflammatory syndrome: association with a persistence of specific IGM antibodies]. AB - We report 9 cases of enteroviral infection associated with systemic inflammatory disease (including 4 cases of vasculitis, 1 case of periarteritis nodosa, 1 case of Sharp's syndrome). We then reviewed 36 cases of enteroviral infection with persistent IgM antibodies diagnosed in the virology laboratory in a 6-year period: among them 11 cases were found to present with subacute or chronic inflammatory disease. We conclude that enteroviruses might be important triggers of systemic inflammatory disease. PMID- 8009058 TI - [Evaluation of primary amyloidosis using scintigraphy with the serum amyloid P component: from diagnosis to prognosis]. AB - Purified human SAP labeled with iodine-123(123I-SAP) was given intravenously to 24 patients with biopsy-proved systemic primary amyloidis. Spleen and liver distribution of amyloidis is mostly revealed by 123I-SAP scintigraphy and the importance of retention may be correlated with the survival. PMID- 8009059 TI - [Pulmonary pneumocystosis in immunodepression: apropos of 78 consecutive cases seen at the CHRU of Clermont-Ferrand from 1984 to 1993]. AB - 78 consecutive cases of PCP have been analysed: 59 (75.6%) cases were associated with HIV infection and 19 (24.4%) cases were associated with solid tumors and hematologic malignancies at advanced stage of the disease and renal transplantation. It could suggest primary prevention for such patients. PMID- 8009060 TI - [Effects of blood transfusion on the serum assays of iron, the total binding capacity of transferrin, vitamin B12 and folates]. AB - To evaluate the influence of blood transfusion on the serum levels of different nutrients, the levels of total iron binding capacity, ferritin, cobalamin and folate were determined before and 24 hours after 2 or 3 packed red cell transfusions, by forty patients with anemia of various causes. No significant change was found in these levels before and after blood transfusion, except for iron and folate. PMID- 8009061 TI - [Idiopathic antehypophyseal insufficiency in the elderly: apropos of 6 cases]. AB - The diagnosis of idiopathic hypopituitarism in the elderly is difficult and often unrecognized. We report 6 cases. PMID- 8009062 TI - [Secondary hyperparathyroidism in hospitalized aged patients: apropos of 200 assays of intact parathyroid hormone]. AB - Plasma intact parathyroid hormone (PTH) determinations were performed in 200 elderly patients admitted in a geriatric care unit. Abnormally high levels of PTH were observed in 40 subjects. There was a significant correlation between plasma ionized calcium determinations or creatinine clearance and PTH levels. Subjects with high PTH levels exhibited constantly reduced levels of 25 OH-D3. A calcium and vitamin D supplement, performed in 13 patients, was constantly followed by a decrease of the PTH level. PMID- 8009064 TI - [Fracture of the sacrum caused by bone insufficiency in the elderly: apropos of 14 cases]. AB - We report a series of 14 elderly patients with sacral insufficiency fractures of the sacrum. All patients presented with pain in low back, pelvis or lower limb which was often misleading. Bone scintigraphy was diagnostic in all the patients. Outcome was favourable in all the cases. PMID- 8009063 TI - [Modalities of detection of abnormal blood level of thyroid hormones in hospitalized aged patients]. AB - In a continuous series of 3836 patients over 60 years old, 24.1% have abnormal tests, 1.28% present hyperthyroidism and 1.98% hypothyroidism. Screening with TSH alone and T4 if abnormality, appears as the most helpful and costless method in order to detect thyroid dysfunction in hospitalised elderly patients. PMID- 8009065 TI - [Nutritional and trace elements status in cardiomyopathies in the elderly]. AB - Nutritionnal status remain poor in hospitalized elderly for cardiopathy compared to healthy controls, secondary to bad general status. Selenium rate appears significantly lower in ischemic cardiomyopathy than in valvular or hypertension cardiopathy. PMID- 8009066 TI - [Diagnosis of amyloidosis in the elderly: value of the aspiration of the abdominal subcutaneous fat. Prospective study apropos of 100 cases]. AB - Study of the presence of amyloid deposits on subcutaneous fat aspirates was carried out in 100 patients hospitalized in a geriatric unit. The test was positive in 15%, and in 4% of them, amyloid deposits were also seen on accessory salivary glands, confirmed by immunohistochemical staining. These results indicate that sub-cutaneous fat aspirate may be a useful test for an early diagnosis of amyloidosis. PMID- 8009067 TI - [Rheumatoid polyarthritis in the elderly--rhizomelic pseudopolyarthritis: what differences?]. AB - The authors have conducted a comparative retrospective study between polymyalgia rheumatic (N = 26) and rheumatoid arthritis in the elderly (N = 44), including HLA DRB1 genotype determination by PCR-RFLP analysis. No clinical nor biological differences were significant between the 2 groups of patients. However 70% of RA patients had one ore more susceptibility alleles (shared epitope hypothesis) and 50% in polymyalgia rheumatica. PMID- 8009068 TI - [Outcome of 161 patients with systemic diseases after their admission in intensive care unit]. PMID- 8009069 TI - [Potential risks of the withdrawal of corticoids in Horton's disease. Prospective study of 22 patients]. AB - We carried out a prospective study on stopping steroid use in 22 cases of giant cell arteritis. 30% had transitory insufficient adrenal function. CD8 cells monitoring may be useful in order to decide withdrawing steroids. PMID- 8009070 TI - [Role of high-dose polyvalent immunoglobulins in the treatment of dermatopolymyositis: treatment of first intention or of salvage?]. PMID- 8009071 TI - [Long-term results of the treatment of diffuse systemic scleroderma with interferon-gamma]. AB - There are very few drugs effective in the treatment of diffuse scleroderma and therefore we conducted an open study with gamma interferon. Among 20 diffuse scleroderma, evolving since less than 3 years, an improvement was observed in 8 patients. There was no serious side effect. Survival of these 20 patients was 85% at 5 years. PMID- 8009073 TI - [The appearance of antinucleosome antibodies precedes that of anti-double stranded DNA and anti-histones in murine lupus]. AB - Collected samples serum of 30 MRL lpr/lpr and 15 MRL MP +/+ were tested by ELISA on purified mononucleosomes and its individual components, dsDNA and histones. Anti-mononucleosome antibodies can be detected as early as 10 and 23 week of age for MRL lpr/lpr and MP +/+, respectively, and arose before anti-dsDNA and anti histone antibodies. PMID- 8009072 TI - [Immunogenetics of systemic lupus: adequacy between HLA molecules class II and the germinal genes of antigen receptor of T-lymphocytes favours the production of various antibodies]. AB - The study of 30 patients with systemic lupus and of 153 relatives failed to show any differences in HLA and TCR beta haplotype frequencies between patients and relatives. A significant interaction between TCR V beta and HLA-DR/DQ genes in the response to the peptide U1-RNP A 35-58 was demonstrated. PMID- 8009074 TI - [Is male infertility caused by congenital bilateral atrophy of the vas deferens a clinical form of mucoviscidosis?]. AB - We investigated clinical data, sweat electrolytes and cystic fibrosis (CF) mutations in twelve patients with congenital bilateral aplasia of vasa deferentia (CBAVD) to debate arguments for diagnosing CF. Sweat chloride concentration was definitely raised in four patients. Three patients are CF compound heterozygotes. Six patients are CF heterozygotes. This result reinforces the hypothesis that white males with CBAVD might have a mild form of CE. PMID- 8009075 TI - [Oxyntomodulin, a new hormonal marker of intestinal malabsorption syndromes]. AB - Plasma oxyntomodulin-like immunoreactivity (OLI) concentrations were found to be significantly elevated in 6 patients with coeliac disease when compared with those observed in 38 healthy subjects. Furthermore, OLI hypersecretion is related to the degree of malabsorption. This marker could be used as a test for detection and follow-up of patients with malabsorptive disorders. PMID- 8009076 TI - [Presymptomatic detection of familial colonic polyposis]. AB - In familial adenomatous polyposis coli (APC) it is possible to detect APC carriers either by research of bilateral congenital hypertrophy of the retinal pigment epithelium (CHRPE) or by genetic diagnosis (APC gene is localized in 5q21). These detections were performed in 33 patients of four families with the same positivity for genetic typing (11 patients) or for CHRPE (11 patients) which thus avoided annual coloscopy. PMID- 8009077 TI - [Generalized edema caused by licorice: a new syndrome. Apropos of 3 cases]. AB - Licorice abuse is a wellknown cause of high blood pressure, myopathy, and cardiac rhythm trouble. It should be considered as a cause of diffuse acute edema, as shown in the three following case-reports. PMID- 8009078 TI - [Neurologic manifestations in Lyme disease. Apropos of 22 cases]. AB - The main clinical and biological features of 22 cases of neurological forms of Lyme disease are reviewed. Radiculitis (n = 15), cranial nevritis (n = 7), meningitis (n = 5) and encephalitis (n = 4) are often associated. Tick bites were previously noticed in only 40% of cases; erythema chronicum migrans in 73%, "one to six months before the onset of neurological symptoms". Titers of Borrelia Burgdorferi antibodies were always above 1/256. Among 18 patients, DR W2 HLA haplotype was present in 15. PMID- 8009079 TI - [A new threat: Xanthomonas maltophilia infection. Apropos of 50 cases]. AB - In an attempt to further characterize infections due to Xanthomonas maltophilia (XM), we reviewed 50 case reports observed in our institution. XM is emerging as an important nosocomial pathogen in immunocompromised patients, especially those receiving broad spectrum antimicrobial antibiotherapy. Distinction between colonisation and infection is often difficult. XM presents a therapeutic challenge because of its tendency to exhibit multiple resistance. PMID- 8009080 TI - [Prolonged decrease of prothrombin level caused by rodenticide poisoning. Apropos of 3 cases]. AB - We report three cases of intoxication with anticoagulant rodenticides. This intoxication leads to prolonged hypocoagulability despite vitamin K therapy. In our patients, the side effect was present for 2 to 3 months. PMID- 8009081 TI - [Fibromyalgia disclosing Gelineau's disease: apropos of 2 cases]. AB - Sleep abnormalities are frequently reported as possible etiopathogenic factor of fibromyalgia. We report 2 cases of fibromyalgia revealing a long-standing narcolepsycataplexy. PMID- 8009082 TI - [Corticotropic macroadenoma: clinical, hormonal, radiological and immunocytochemical study of 6 cases]. AB - We report 6 cases of corticotroph macroadenomas which show heterogeneity of clinical and biological features (from Cushing's syndrome to silent adenoma) and heterogeneity of immunocytochemical staining. One patient reported on had skin hyperpigmentation and ACTH hypersecretion without clear abnormal adrenocortical function; we believe that this patient's plasma contained ACTH with very low bioactivity. PMID- 8009083 TI - [Hyperthyroidism caused by inappropriate secretion of TSH. Apropos of 2 new cases]. AB - Hyperthyroidism due to inappropriate secretion of TSH is rare. It may be due to either TSH-secreting pituitary adenomas (n = 15) or selective pituitary resistance to thyroid hormone action (n = 31). The recognition of these patients is of great clinical importance since they should be treated differently than patients with more common forms of hyperthyroidism (Graves' disease, autonomous thyroid nodule). PMID- 8009084 TI - [Thyroid pathology and multiple autoimmune syndrome: clinical and immunogenetic aspect, apropos of 11 cases]. AB - The authors report 11 cases of multiple autoimmune syndromes. Autoimmune thyroid disorders and Sjogren's syndrome seem to be non-randomly associated and might share a genetic predisposition linked to HLA phenotype B8 DR3 and B12 DR4. PMID- 8009085 TI - [Insulin-dependent diabetes and organ specific autoimmune diseases: a retrospective clinical and immunogenetic study of 165 consecutive cases]. AB - We analysed clinical and immunological indexes in 165 caucasian adult patients presenting insulin-dependent diabetes mellitus associated with other organ specific autoimmune diseases (type Ib IDDM). As diagnostic strategy, we recommend testing thyrogastric autoantibodies at diabetes onset and islet-cells antibodies three years after. PMID- 8009086 TI - [Evaluation of the participation of proinsulin in hyperinsulinism in patients with obesity and glucose intolerance]. AB - The comparison of the results of two insulin assays, a RIA using a polyclonal antibody and a EMIA using two monoclonal antibodies in blood samples collected during an oral glucose load in normal, obese, glucose intolerant and type II diabetic patients indicated that hyperinsulinemia of obese and glucose intolerant patients is not associated to increased proinsulin/insulin ratio. PMID- 8009087 TI - [Relationship between lipoprotein(a) and non-insulin-dependent diabetes in 602 patients]. AB - Lipoprotein (a) status has been evaluated in a population of 602 non insulin dependent diabetics and compared to 74 healthy controls. There was no significant difference in concentration and no obvious influence of glycaemic, coronarian or renal status. PMID- 8009088 TI - [Gaucher's disease type 1: apropos of 17 cases]. AB - Gaucher's disease is characterized by accumulation of glucocerebroside (caused by an autosomally inherited deficiency of glucocerebrosidase) in the cells of the reticuloendothelial system. We report the clinical, laboratory, radiologic features of 17 patients with type 1 Gaucher's disease. PMID- 8009089 TI - [Course of a case of Gaucher's disease type 1 treated over a year with glucocerebrosidase (Ceredase)]. AB - Gaucher's disease is caused by a deficiency of glucocerebrosidase. Enzyme replacement therapy with glucocerebrosidase (Ceredase) is available in France since 1991. We report the clinical effectiveness in a woman with type 1 Gaucher's disease treated with the enzyme for one year. Hepatomegaly regressed, bone pain decreased but improvement of severe skeletal manifestations were slow and incomplete. PMID- 8009090 TI - [Evaluation of the epidemic caused by the human immunodeficiency virus in Cambodia]. AB - The infection by the human immunodeficiency virus is in the process of expanding to a dramatical level in South East Asia. At the moment, the few available datas on Cambodia are increasingly worrying, with a rate of seropositivity of prostitutes higher than 9% in 1992 and a clear progression of the rate of seropositivity of blood donors: 1.3% by the second quarter of 1993. PMID- 8009091 TI - [HIV infection in intravenous drug addicts]. AB - Clinical course of HIV infection was studied among 156 intravenous drug users (IVDU). Mean follow up was 22.7 months. Characteristics of HIV infection in IVDU were frequent oral candidiasis and bacterial infections (BI), more frequent progression to AIDS after a second BI, rapid decline of CD4+ in a group of current IVDU. Progression to AIDS was 14.5% per year, not different among current and former IVDU. Twenty five IVDU died. PMID- 8009092 TI - [Behaviors at risk of the intravenous drug addicts and prevention of HIV infection]. AB - Needle sharing and sexual behaviour were studied in 396 intraveinous drug addicts (IVDA). Only 20% stopped needle sharing and used condoms. They were 6% before 1990 and 23% after. Both preventive measures were adopted by 32 of 78 HIV positive and only 25 of 210 HIV negative IVDA. Attention is drawn on the need for specific measures for prevention of heterosexual transmission of HIV infection by IVDA. PMID- 8009093 TI - A heavy me(n)tal problem? PMID- 8009094 TI - Acute illnesses in children. A description and analysis of parents' perception of illness threat. AB - OBJECTIVES: To identify families in which the parents reported the child's illness as particularly stressful (high perception of illness threat), and to find out which health problems the parents perceive as particularly threatening. DESIGN: The parents registered the diagnosis and perception of illness threat in relation to the child's latest illness within a four-week retrospective period. Selected psychosocial conditions of the families were recorded in the same questionnaire. SETTING: 18,949 families with at least one child under the age of 8 years, resident in the County of Ringkobing in western Denmark at 1 March 1988. SUBJECTS: An age-stratified random sample of 1982 families was entered in the study. 85% of the families returned the questionnaire. RESULTS: There was a considerable variation in the parents' perception of illness threat. On the basis of a score it was possible to group parents with a high, medium, and low perception of illness threat. Every fourth family reported a high perception of illness threat. A multivariate analysis, with a high perception of illness threat as dependent and selected psychosocial conditions and the diagnosis as independent variables, led to the following main results: 1) parents with a high perception of the general health threat ("worried" parents) most frequently reported a high perception of illness threat, 2) the diagnoses were decisive; in particular, inflammation in the middle ear, bronchitis, pneumonia, and accidents led to the parents' reporting a high perception of illness threat, 3) parents without experience of children and children's illnesses more frequently perceived an actual illness as a high illness threat than parents with this experience, 4) parents more frequently perceive an illness in girls as a high illness threat. CONCLUSIONS: "Worried" parents, without experience of children and children's illnesses, perceive the child's latest illness as a high illness threat. These families need special care. PMID- 8009095 TI - Cancer prevalence in Israeli family practice. The Cancer Research Group. AB - OBJECTIVES: To study the prevalence of different cancers in several communities in Israel, using data supplied by family physicians, and compare these with the data from the National Cancer Registry. The attendance pattern of cancer patients at the family practice and consultation clinics was also studied. DESIGN: 17 family physicians reported on all living cancer patients under their care. SETTING: 15 family practices in northern Israel, urban and rural, Jewish and Arab. SUBJECTS: The study population included nearly 26,000 patients. OUTCOME MEASURES: Standardised prevalence rates of cancer for different types of cancer and for different communities (per 1000 people at risk); duration of survival since the diagnosis. RESULTS: 249 cancer patients were identified, excluding 130 with basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) of the skin, giving a prevalence of 9.6/1000 (excluding BCC and SCC). This is lower than that of the few reports found in the literature. Half of the cancer patients in the study had survived over five years since the diagnosis. Marked differences were found between the Jewish and Arab populations, with standardized prevalence of less than half among the Arabs. Significant differences were also found between the different types of Jewish community, kibbutzim having a rate three times higher than any of the others. A comparison of the data from the study with those of the Israel National Cancer Registry showed 50% more cases known to the ambulatory system. Half of this discrepancy is inexplicable. CONCLUSIONS: Data collection in cancer care should be supplemented from primary care sources. Larger studies, with emphasis on registration quality control, are required, to explain some of the differences found in cancer prevalence between different communities. PMID- 8009096 TI - Identified and unidentified mental illness in primary health care--social characteristics, medical measures and total care utilization during one year. AB - OBJECTIVE: To screen patients in general practice with regard to identified and unidentified mental illness, and to describe social and demographic profiles of the two groups and their medical measures and total care utilization. DESIGN: Cross sectional study of 333 consecutive patients with one year follow-up. SETTING: Two primary health care units in a Stockholm suburb area. PARTICIPANTS: Patients 18 years and older. MAIN OUTCOME MEASURES: Mental illness according to either ICD-9 diagnosed by GPs (identified cases) or when not identified by GPs according to a self-assessment questionnaire HSCL-25 with cut-off point 1.75 (unidentified cases). RESULTS: In comparing identified (15.3%) and unidentified patients (11.7%) with other patients (No mental illness) no differences were found in demographic antecedents. Social problems existed in 31% of identified, 49% in unidentified, and 14% in patients with no mental illness. Sick-listing and issuing of prescriptions were more frequent in patients with identified mental illness. The one year follow-up study also showed over-utilization of care in these patients. The psychiatric services were sought by about one fifth of both the patient groups with mental illness, which is to a significantly greater extent than for patients without mental illness (2%). CONCLUSION: Patients with self-assessed mental illness not identified by GPs are not deemed to be "over medicalized" nor to overload care-services, while patients identified by GPs with a diagnosis of mental illness receive a lot of medical input and require much care. Psychosocial inputs for the latter group within primary care can presumably reduce unnecessary utilization of resources. PMID- 8009097 TI - Dental restorative materials and the prevalence of eczema, allergic rhino conjunctivitis, and asthma in schoolchildren. Dental amalgam and allergy in schoolchildren. AB - OBJECTIVE: To study the association between allergic diseases (eczema, allergic rhino-conjunctivitis, and asthma) and different types of dental restorative materials (amalgam, composite, and glass ionomer) in Swedish schoolchildren. DESIGN: Cross-sectional survey with a questionnaire asking for symptoms of allergic disease during the previous year. This information was combined with current dental status (number and type of filled tooth surfaces). SETTING: Primary care and a school in the centre of a middle-sized Swedish town (approx. 80,000 inhabitants). PARTICIPANTS: 348 pupils of both sexes 13-15 years old. OUTCOME MEASURES: The occurrence of allergic disease in pupils with and without dental fillings of different types. The mean number and type of filled tooth surfaces in diseased and healthy pupils. RESULTS: 44% of the pupils had no amalgam fillings. This group of children reported significantly more often asthmatic symptoms than the group with amalgam (P = 0.02). The asthmatic children had a lower mean number of amalgam surfaces than the other pupils (P = 0.002) and also a lower mean number of filled tooth surfaces of all types. CONCLUSION: The results of this study do not support the theory that amalgam fillings increase the prevalence of allergic diseases or allergic reactivity as such in schoolchildren. Neither do composite and glass ionomer seem to cause such complications. PMID- 8009098 TI - Detection of retinopathy by non-mydriatic fundus photography in diabetics treated with oral hypoglycaemic agents or diet. AB - OBJECTIVE: To determine the prevalence of retinopathy by non-mydriatic fundus photography in diabetics treated with oral hypoglycaemic agents or diet. DESIGN: Cross-sectional survey of diabetes-induced fundal changes assessed by fundus photography. SETTING: Area of Health Centre of Oulu. Population 100,000. SUBJECTS: All 1,228 diabetic patients, aged 30 years or over and treated with oral hypoglycaemic agents or diet at the Health Centre of Oulu. MAIN OUTCOME MEASURES: Presence and severity of diabetic retinopathy in fundus photographs, need for laser photocoagulation, age, hypertension, body mass index (BMI), duration of diabetes, type of treatment of diabetes. RESULTS: Retinopathy was observed in 178 (18%) of those 1,015 diabetics examined at the health centre. Retinopathic changes requiring laser treatment were observed in 15 cases, and eight of them had not been diagnosed earlier. Sixty non-attenders photographed at the Central University Hospital were also included, and 12 of them had retinopathy. The presence of retinopathy was associated with long duration of diabetes, poor glycaemic control, and high systolic blood pressure. No association was detected with sex, age at onset of diabetes, BMI, medication for coronary artery disease, or hypertension. CONCLUSIONS: Non-mydriatic fundus photography detected a high prevalence of retinopathy in diabetic patients. Half of those with preproliferative changes were previously undiagnosed cases, and five were in need of immediate laser treatment. It is concluded that fundus photography is a useful tool for detecting retinopathy in a primary health care setting. PMID- 8009099 TI - Pulmonary cancer from the general practitioner's point of view. Experience from the health centre area of Kungsbacka, Sweden. AB - OBJECTIVE: To study the incidence of pulmonary cancer in a community with special reference to the diagnostic process and the role of the general practitioner. DESIGN: Study of the records of all patients within the community with pulmonary cancer reported to the Swedish Cancer Registry during the years 1980-1984. SETTING: The community of Kungsbacka in southwestern Sweden with about 48,000 inhabitants. PARTICIPANTS: 40 subjects with pulmonary cancer. OUTCOME MEASURES: Incidence, main symptoms, level of care, doctor delay, survival rate. RESULTS: The incidence was 16 per 100,000 per year. Most patients first visited a general practitioner. Most common initial symptom was cough. Mean doctor delay was 12.5 weeks. The five-year mortality rate was 95%. CONCLUSION: The high mortality emphasizes the importance of an early diagnosis. The general practitioners are very important in the diagnostic process. PMID- 8009100 TI - Varieties of functional assessment in physiotherapy. AB - OBJECTIVE: To increase our knowledge about the diagnostic process in physiotherapy and to identify possible differential frames of reference. DESIGN: Video-recordings and semi-structured interviews of the participants. SETTING: Natural working settings, i.e. private institutes and patients' homes. PARTICIPANTS: Manual, psychomotor, and district (visiting) therapists. RESULTS: The three categories of therapists use different approaches and operate within different interpretative frames throughout. They direct their attention towards different aspects of the patient's body, function, and life situation, they interpret information differently, they conclude their examinations in different ways, and suggest different treatments. The observed dissimilarities are generally mirrored by the therapists' verbal statements. But certain discrepancies between actions and statements are also found. CONCLUSION: This study shows how practice and the way of thinking can differ among physiotherapists. Renewed reflection on actual practice is called for, and the diagnostic process should be approached as an active interpretive enterprise. PMID- 8009101 TI - Intervention against ischaemic heart disease risk factors in primary health care in a semi-rural community. The population study "50-year-old people in Kungsor". AB - OBJECTIVE: To see whether a program for screening and intervention against ischaemic heart disease (IHD) risk factors could be integrated into the ordinary work of a primary health care centre. DESIGN: Longitudinal population study with baseline screening, intervention, and one-year follow up. SETTING: Kungsor, a semi-rural community in mid-Sweden. PARTICIPANTS: All 50-year-old men and women in Kungsor. MAIN OUTCOME MEASURES: Feasibility, participation rate, change of traditional IHD risk factors and self-assessed well-being measures. RESULTS: Blood pressure and serum cholesterol were significantly reduced. Smoking rates and BMI were not affected. The advice given had the same effect, whether given by the doctor or the nurse. Videotaped information had no further effect on the risk factor levels. There was no obvious evidence of negative psychological effects of screening and intervention. CONCLUSIONS: Primary health care provided an excellent base for the study and the project could be performed within the ordinary setting. The risk reduction was of a similar magnitude to that in the large-scale preventive trials without any evidence of negative psychological effects of screening and intervention. PMID- 8009102 TI - Allergic diseases, dental health, and socioeconomic situation of Swedish teenagers. Allergy, dental health, and social situation. AB - OBJECTIVE: To study the association between allergic diseases (eczema, allergic rhino-conjunctivitis, and asthma), dental health, and the socioeconomic situation of Swedish teenagers. DESIGN: Cross-sectional survey with a questionnaire for allergic symptoms and parents' occupation (for socioeconomic classification); current dental status from the Public Dental Service. Bronchial reversibility test. Telephone inquiry of asthma cases. SETTING: Primary care and a school in the centre of a middle-sized Swedish town (approx. 80,000 inhabitants). PARTICIPANTS: 137 pupils of both sexes, 13-15 years old. MAIN OUTCOME MEASURES: Number of reported cases with allergic disease and outcome of bronchial reversibility test in relation to social class. Number of validated cases of asthma. Number of filled tooth surfaces in healthy and diseased cases. RESULTS: Socioeconomic situation was found to associate with dental health, i.e. more fillings in lower social classes (P = 0.01), and with allergic disease, i.e. asthma and rhino-conjunctivitis (P = 0.05). Individuals from the upper social classes seemed prone to overreport asthmatic symptoms, whereas teenagers in the lower classes did the opposite, as indicated by five cases of pathologic values after bronchial reversibility tests in individuals who did not report asthmatic symptoms. CONCLUSION: The study indicates that socioeconomic situation associates significantly with both dental health and allergic disease. No association was found between dental health and allergic diseases. PMID- 8009103 TI - Once hypertensive, always hypertensive? A three year follow-up after stopping medication. AB - OBJECTIVE: To verify the existence of hypertension in a group of long-term pharmacologically treated hypertensives and to evaluate the possibility of discontinuing their medication. DESIGN: The diagnosis of hypertension was established when after a wash-out period (one month) the blood pressure measured at three consecutive examinations, with at least one week interval between them, was always higher than WHO's reference levels for the diagnosis of hypertension. Those who did not fulfil these criteria would continue, with regular controls, without medication as long as clinically indicated. The final evaluation was done after a three year follow-up. SETTING: The out-patient Hypertensive Unit of the Department of Geriatrics, Skelleftea Hospital, Sweden. PARTICIPANTS: 86 out patients (33 males and 53 females) aged 68 to 82 years (mean 74) with long-term hypertension sent to our unit by general practitioners in our health district (population 80,000). RESULTS: 34 of the initial 86 patients required medication by the end of the wash-out period. The remaining 52, 16 males and 36 females, continued without medication and after the three year follow up 14 of them were still without it. There was a striking difference between males and females since a significantly higher number of males than females were free of medication at the end of the period (p < 0.001). In those who restarted pharmacological therapy, the period without medication lasted no longer than five months. CONCLUSIONS: Arterial hypertension can easily be over-represented as a diagnosis if not revised when clinically advisable or if established without accurate criteria. The possibility of stopping the antihypertensive medication in old patients is worth considering, particularly in male patients. The dangers of such strategy are practically minimal when regular controls are undertaken during the attempt. PMID- 8009105 TI - [Continuity of care]. PMID- 8009104 TI - Acute maxillary sinusitis in general practice: a decision problem. AB - OBJECTIVE: This paper describes a qualitative analysis of a decision problem of acute maxillary sinusitis in general practice. The criteria and expected outcomes on which general practitioners (GPs) base their choice of a management strategy are presented. DESIGN: Structured open-ended interviews, all done by the first author, were transcribed, and summarized for each management strategy. These summaries were sent back to the experts for verification. PARTICIPANTS: Eight expert GPs from The Netherlands participated; all had been practising for at least three years, and had conducted postgraduate research into upper respiratory tract infections. RESULTS: There was a high degree of consensus among the eight GPs. While most practitioners generally considered the prevention of complications of therapy more important than the prevention of complications of disease, patients at risk (e.g., the elderly, children, patients with other chronic diseases, and patients in weakened condition) of complications of acute sinusitis (e.g., chronic sinusitis) were considered an exception to this rule, possibly because the complications of sinusitis are more serious than those of its therapy. Major differences between the GPs concerned the timing of decisions (e.g. prescribing antibiotics after 5 or 21 days of complaints while local therapy was used). CONCLUSION: Although this study gives no answer as to which management strategy is optimal, the results served as a basis in the development of the Dutch "Sinusitis in general practice standard". In order further to develop the optimal strategy, in future research, the probabilities and weights attached to the criteria and expected outcomes have to be quantified. PMID- 8009106 TI - [Consent to gerontological surgical care]. PMID- 8009107 TI - [Perioperative nutritional requirements]. PMID- 8009108 TI - [Making the students aware of geriatric care]. PMID- 8009109 TI - [Upper digestive hemorrhage. Management of cirrhotic patients]. PMID- 8009110 TI - [A developing function]. PMID- 8009111 TI - [Needle biopsy of the liver by the intercostal approach]. PMID- 8009112 TI - [Percutaneous endoscopic gastrostomy]. PMID- 8009113 TI - [Bioethics in initial education]. PMID- 8009114 TI - [Access paths to the kidneys. The transperitoneal approach]. PMID- 8009115 TI - [A specific role. Geriatric nurse]. PMID- 8009117 TI - [Primary bronchopulmonary neoplasms. Surgical principles]. PMID- 8009118 TI - [Preoperative preparations]. PMID- 8009116 TI - [The elderly patient in the operating suite]. PMID- 8009119 TI - [The operating suite. Preparation of the patient]. PMID- 8009120 TI - [Return from the operating room]. PMID- 8009121 TI - [Exercise therapy]. PMID- 8009122 TI - [Reception of the patient into the operating suite. A factor of importance for a quality anesthesia]. PMID- 8009124 TI - [Patients in the recovery room. Reception by the nursing team]. PMID- 8009123 TI - [Primary bronchopulmonary cancers. Epidemiology, pathological anatomy, etiology]. PMID- 8009125 TI - [Primary bronchopulmonary cancers. Diagnosis and therapeutic balance]. PMID- 8009127 TI - [Ambulatory surgery in army hospitals]. PMID- 8009126 TI - [Ambulatory surgical center. Organization and function]. PMID- 8009128 TI - [Ambulatory surgery in a university hospital center: administrative, economic and financial aspects]. PMID- 8009129 TI - [Administrative and financial problems in the private sector]. PMID- 8009130 TI - [Ambulatory surgery and responsibility]. PMID- 8009131 TI - [A nursing diagnosis. Fatigue]. PMID- 8009132 TI - [Anesthesia and ambulatory surgery. Facts and reflections]. PMID- 8009133 TI - [The adrenal glands. Approaches]. PMID- 8009134 TI - What is exertion-related sudden cardiac death? PMID- 8009136 TI - Effects of taper on swim performance. Practical implications. AB - Competitive swimmers commonly focus upon optimising performance at a single competition. A period where training volume is incrementally reduced or "tapered" often precedes such a competition. The use of taper is justified as increases in muscular power, and the restoration of plasma haematocrit, haemoglobin and creatine kinase are evident with this training reduction. A consistent performance improvement of approximately 3% has also been reported with taper in competitive swimmers. However, there are limitations in terms of what comprises a successful taper schedule. It appears that a taper which improves performance involves a substantial (60 to 90%) graded reduction in training volume, and daily high intensity interval work over a 7- to 21-day period. Training frequency should be reduced by no more than 50%; a more conservative estimate would be to reduce frequency by approximately 20%. Optimal performance is likely when the reduction in training frequency is combined with the qualitative knowledge of the coach and/or athlete during taper. PMID- 8009137 TI - Exercise training in sweat clothing in cool conditions to improve heat tolerance. AB - Training in sweat clothing in cool conditions has appeal as the most practical and exercise-specific method of improving heat tolerance when athletes cannot achieve natural acclimation to hot conditions prior to competition. However, both early and more recent studies have not provided sufficient evidence to allow a conclusive endorsement of this method. Despite this, it is apparent that training in sweat clothing in cool conditions can induce levels of thermal strain in trained individuals which are very similar to those experienced when the same exercise is performed in hot-humid conditions. Certainly, training in sweat clothing in cool conditions is preferable to attempting no artificial acclimation measures, although statistically significant improvements in heat tolerance beyond those induced by the training itself are rare. PMID- 8009135 TI - Clinical consequences of athletic amenorrhoea. PMID- 8009140 TI - [Beta-interferon and multiple sclerosis]. PMID- 8009139 TI - Optimisation of sprinting performance in running, cycling and speed skating. AB - Sprinting performances rely strongly on a fast acceleration at the start of a sprint and on the capacity to maintain a high velocity in the phase following the start. Simulations based on a model developed in which the generation of metabolic power is related to the mechanical destinations of power showed that for short-lasting sprinting events, the best pacing strategy is an all out effort, even if this strategy causes a strong reduction of the velocity at the end of the race. Even pacing strategies should only be used in exercises lasting longer than 80 to 100 seconds. Sprint runners, speed skaters and cyclists need a large rate of breakdown of energy rich phosphates in the first 4 to 5 seconds of the race (mechanical equivalent > 20 W/kg) in order to accelerate their body, and a power output of more than 10 W/kg in the phase following the start to maintain a high velocity. Maximal speed in running is mainly limited by the necessity to rotate the legs forwards and backwards relative to the hip joint. The acceleration phase, however, relies on powerful extensions of all leg joints. Through a comparison of the hindlimb design of highly specialised animal sprinters (as can be found among predators) and of long distance animal runners (as found among hoofed animals), it is illustrated that these 2 phases of a sprint rely on conflicting requirements: improvement of maximal speed would require lower moments of inertia of the legs whereas a faster acceleration would require the involvement of more muscle mass (not only of the hip and knee extensors but also of the plantar flexors). Maximal speed in cycling and speed skating is not limited by the necessity to move leg segments but rather on air friction and rolling or ice friction. Since the drag coefficients found for speed skaters and cyclists (about 0.8) are considerably higher than those of more streamlined bodies, much progress can still be expected from the reduction of air friction. Speed skaters and especially cyclists show much smaller accelerations during the start than do sprint runners. Skaters might try to improve their very first push off by developing a start technique that allows a much more horizontally directed propulsive force. The small propulsive force at the onset of a cycling sprint is due to the gearing system.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8009138 TI - Regulation of neutrophil function during exercise. AB - In recent years there has been considerable interest in how exercise and training may affect the immune system. There is now substantial cross-sectional and epidemiological evidence that exercise causes significant changes in the distribution and function of a number of cellular and humoral immune parameters. Neutrophils represent one of the key nonspecific host defence cell populations responsible for the phagocytosis of many microbial, bacterial and viral pathogens. The neutrophil is also known to be involved in the synthesis and release of immunomodulatory cytokines that influence both T cell and B cell activities. Therefore, it plays an important role in both the efferent (phagocytosis and degranulation) and afferent (release of immunomodulatory molecules) limbs of the immune response. Neutrophils and macrophages respond both to phagocytosable particles (e.g. bacteria, viruses and cell debris) and to a number of soluble factors. There is an increase in the number of circulating neutrophils with exercise as a result of demargination of cells from endothelial tissues (mediated by catecholamines) and bone marrow (mediated by cortisol), or as part of the phagocytic and inflammatory response to exercise-induced tissue damage. Following exercise-induced mobilisation into the circulation and migration into tissues, neutrophils undergo adherence, phagocytosis (engulfment) of bacteria or tissue fragments, degranulation of cytoplasmic granules and, ultimately, activation of the respiratory burst. The capacity of the respiratory burst largely determines the cytotoxic potential of the neutrophil. The respiratory burst involves a sudden increase in nonmitochondrial oxidative metabolism, resulting in the production of the superoxide anion (O2-) and other reactive oxygen species by the nicotinamide adenine dinucleotide phosphate (NADPH) oxidase enzyme complex located at the plasma membrane. Although the biochemistry of the respiratory burst has been well studied, the mechanisms by which exercise and training may influence its activity are not well characterised or understood. Studies on the acute effects of exercise show that exercise generally elicits an initial activation of neutrophils-evidenced by release of cytoplasmic enzymes (degranulation) with secondary changes in key effector functions such as the phagocytic and respiratory burst activity. The nature of the functional changes is still unclear, as some studies show a transient suppression of the respiratory burst and/or phagocytic capacity immediately after exercise, while others report that moderate intensity exercise elicits an enhanced response. The variability in findings may be attributable to differences in the age, gender and initial fitness levels of the people studied, the intensity and duration of the exercise protocols used, and the different methodological procedures employed.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8009141 TI - [Symptomatic heterozygotic adrenoleukodystrophy in adults. 10 cases]. AB - Adult adrenoleukodystrophy is a X-linked peroxisomal disease associated with the accumulation of very long chain fatty acids (VLCFA) in tissues and body fluids. The diagnosis is established on the demonstration of elevated VLCFA in blood and cultured skin fibroblasts. Women are affected in nearly 15% of cases and neurological symptoms and/or signs develop in 53% of them. Identifying these women is important because of genetic counseling and a possible therapeutic approach. Ten cases of symptomatic heterozygous adult adrenoleukodystrophy are reported. Mean age at the time of diagnosis was 44.6 +/- 9.3 years. All patients presented with spastic paraparesis with inconstant and mild sensory or bladder disturbances. Cognitive impairment was present in 1 case. Cerebrospinal fluid was normal. Adrenal function in response to tetracosactide injection was abnormal in 1/7 cases. Electromyography detected a peripheral neuropathy in 1 case. Somatosensory evoked responses were abnormal in all cases, visual and auditory evoked responses in respectively 3/6 cases and 3/4 cases. Brain MRI detected non specific abnormalities in 3/7 cases; spinal cord MRI was normal in 3/3 cases. The familial history was helpful for the diagnosis in 3/10 cases. Examination of pedigrees detected 5 hemizygous and 1 asymptomatic heterozygous cases. All the patients were enrolled in a dietary study which adret with low VLCFA is currently under evaluation. PMID- 8009143 TI - [Musical hallucinations: 7 cases]. AB - Musical hallucinations (MH) occurred in 7 patients (5 women and 2 men, age 58-90 yrs) with mild to severe unilateral or bilateral deafness. The hallucinations usually consisted of musical memories (childhood songs, past "hits"). They started abruptly and were identified, sometimes after a period of doubt, as hallucinations. They became "louder" in the silence and, when iterative, could be distressing. By concentrating, 3 patients could change the ongoing tune for another. Elementary (1 case) or verbal (3 cases) auditory hallucinations could be associated and, in one case, vivid visual hallucinations occurred which were not criticized. One patient suffered depression and the MH faded after antidepressive treatment. In the other cases, no psychiatric disorder was identified. Neurological examination, EEGs and brain MRI (in 5 cases) were normal in all but one case, in which MH followed seizures secondary to a left parietal metastasis. Such MH may be termed hallucinosis according to Ey's description. They share some characteristics with other hallucinatory phenomena associated with sensory deprivation, such as the Charles Bonnet syndrome and "pain memories" in phantom limbs. However, the role of deafness, the underlying central mechanisms and psychological factors are poorly understood. PMID- 8009142 TI - [Dissociated preservation of written expression in aphasia with recurrent utterances]. AB - In a female patient, aphasia with recurrent utterances resulted from a double lesion of the left hemisphere, located in the base of the third frontal gyrus and the upper temporal gyri. Predominant in the fluent oral expression was a repeated neologism of which the patient was unaware. The written expression, efficient for lexical entities, was devoid of syntax and had the features of phonological agraphia. Both orally and in written words comprehension was satisfactory but syntactic comprehension was deficient. The stereotyped verbal behaviour could be due to dysfunction of the phonemic programmer. Rupture of the audi-phonatory loop, confirmed by degradation of the verbal working, memory, made this dysfunction worse and accounted for the anosognosia. The participation of the right hemisphere and of the preserved left hemispheric structures in the persistence of various language activities are discussed. PMID- 8009144 TI - [Transient severe orthostatic hypotension and hematoma of the pontine tegmentum]. AB - A 57-year old patient presented with a posterior pontine hematoma and severe postural hypotension. The lesions were localized in the pontine tegmentum. They were bilateral and involved the area of the nucleus reticularis pontis caudalis, left medial lemniscus and roots of several cranial nerves, especially the VIth. The patient had lasting postural hypotension, with reduction of the physiological tachycardia. Investigation of heart rate regulation during manoeuvres however revealed that the accelerating reaction partially persisted, especially with Valsalva manoeuvre. Heart rate recording for 24 hours showed that the physiological nocturnal slowing down reaction had disappeared. In the following months, progressive but limited recovery of blood pressure regulation and accelerating reactions was observed. PMID- 8009145 TI - [Vesical sphincter disorders in Parkinson disease]. AB - Urinary bladder disorders often occur, sometimes very early, during the course of Parkinson's disease. Careful analysis of symptoms including clinical examination, urodynamic studies and radiographic data is essential before choosing a treatment, especially before prostatic surgery. We studied 41 parkinsonian patients. Bladder hyperreflexia occurred in 88% and bladder hyporeflexia in only 12%. In 16 patients, we tested bladder activity after a subcutaneous injection of apomorphine. All patients with hyperreflexia were improved whereas hyporeflexic patients remained unchanged. These findings and data from the literature suggest that in Parkinson's disease detrusor hyperreflexia is the consequence of dopamine nigrostriatal depletion. The physiopathology of bladder hyporeflexia is less understood. The practical care of parkinsonians with urinary disorders is detailed. PMID- 8009146 TI - [3 cases of rare peripheral neuropathies associated with primary Gougerot-Sjogren syndrome]. AB - Several forms of peripheral neuropathy occur in Sjogren's syndrome (dryness of eyes, mouth and other mucous membranes). Symmetrical sensorimotor polyneuropathy occurs most frequently followed by sensory neuropathy. Pure sensory neuronopathy, trigeminal sensory neuropathy and autonomic neuropathy are also common. We report three rare forms of peripheral neuropathy related to Sjogren's syndrome and analyze their clinical course and response to therapy. There were a case of mononeuropathy multiplex (MM), a case of recurrent cranial polyneuropathy (RCP) and a case of chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). The patients were females, 70, 63 and 81 years old respectively. All of them fulfilled the criteria of Sjogren's syndrome, without clinical or serological abnormalities of systemic disease. Only one patient presented with positive antinuclear antibodies. In two patients the onset of neuropathy occurred before the sicca syndrome long. The sural biopsy of the patient with MM exhibited vasculitis of the small vessels and a mild sensory polyneuropathy was superimposed. The patient with RCP had 8 episodes of isolated third nerve palsy and 5 episodes of multiple cranial neuropathy. The patient with CIDP responded poorly to treatment while in the patients with MM and CRP the response to corticotherapy was good. In conclusion, Sjogren's syndrome must be considered in neuropathies of unknown cause not only when they are sensory, autonomic or trigeminal but also when they are recurrent suggesting an ischemic mechanism. Even a CIDP requires a search for Sjogren's syndrome before being considered idiopathic. PMID- 8009147 TI - [Paraneoplastic myasthenic syndrome]. AB - We report a case of neuromuscular disease overlap between myasthenia gravis and Lambert-Eaton syndrome (LES). Clinical features were those of LES and occurred insidiously in this 68-year old man: proximal weakness predominant in the lower limbs, generalized areflexia, dryness of the mouth and partial right eye palsy. Investigations disclosed a small cell lung cancer. On the other hand, an electrophysiological study showed low amplitude of all motor evoked potentials, and significant decrement in the median nerve at repeated 3 Hz stimulation, but failed to disclose any increment of the motor evoked potential in abductor digiti minimi pedis muscle after both maximal voluntary contraction and repeated 20 Hz stimulation. In addition, the patient improved under anticholinesterase drugs, but failed to respond to guanidine. Titres for both anti-acetylcholine-receptor antibodies and calcium channel antibodies were negative. The relationship between our case and recently reported cases of co-existence of the Lambert-Eaton myasthenic syndrome and myasthenia gravis is discussed. PMID- 8009148 TI - [Epilepsy disclosing neuroborreliosis]. AB - After two seizures, a 13 year-old boy experienced headache, fatigue and loss of appetite over a period of 3 weeks. There was a bilateral papilledema with normal visual acuity. CT and MRI disclosed two ischemic foci, that were interpreted as evidence of vasculitis. High serum levels of IgG and IgM antibodies specific to Borrelia burgdorferi, were present. The patient had attended an outdoor scout camp in a area, in south-east Belgium, known to be endemic for tick-born borreliosis. The clinical symptoms, the levels of the specific antibodies and the radiologic abnormalities responded dramatically to treatment. We believe that seizures in this case were related to cerebral vasculitis. This case confirms the extreme diversity of the neurological manifestations of Borreliosis. PMID- 8009149 TI - [Post-traumatic crossed cerebellar atrophy]. AB - A case of crossed cerebellar atrophy after cranial trauma, with a 12-year neuroradiological follow-up is reported. This uncommon cerebellar degeneration has previously been reported only as an autopsic finding. It results from a lesion affecting the contralateral cerebral hemisphere. The role of different cerebro-cerebellar pathways is discussed. PMID- 8009150 TI - [Calcified cerebellar metastasis of carcinoma of the uterine cervix]. AB - A case of calcified cerebellar metastasis from a squamous cell carcinoma of the uterine cervix is reported. The literature on the rare occurrence of both intracranial metastasis from uterine cervix carcinoma and calcifications in intracranial metastasis is reviewed. PMID- 8009151 TI - [Conference at Pitie-Salpetriere hospital. October 1991. Syndrome of dementia and hydrocephalus with slow progress in a 40 year-old woman]. PMID- 8009152 TI - The dimensions of color related to dental porcelain and translucency. PMID- 8009153 TI - Factors in selection and termination of business relationships. AB - This article is one in a constructive series about how dental laboratories and dentists interact. It is aimed toward improving functional relationships to serve the public better. Readers are encouraged to respond in writing about our laboratory series. All members of our professions, including dental laboratory owners, dental technicians and dentists, are invited to participate. Articles in this series are published simultaneously in General Dentistry, journal of the Academy of General Dentistry and Trends & Techniques. PMID- 8009154 TI - A prescription for the construction of a removable partial denture abutment crown. PMID- 8009155 TI - Financial management: a necessary tool for generating cash. AB - This article is an introduction to four types of financial analysis and a foundation for additional exposure to financial analysis. If you don't like working with numbers, consider hiring an accountant or a qualified industry consultant to help you analyze your business. Eventually, you will learn what financial clues to look for when analyzing your business and how to reach your objectives and generate cash to reinvest in your business. PMID- 8009156 TI - Dense titanium castings: the promise fulfilled. AB - The realization that titanium and its alloys possess qualities that would permit the use of a single alloy system for all restorative rehabilitation led a major manufacturer to embark on an extensive Research and Development project to make it feasible. PMID- 8009158 TI - [The immune system and autoaggression]. PMID- 8009157 TI - [Childhood accidents. A study performed in Terrassa]. PMID- 8009160 TI - [Evaluating quality. A condition for efficiency]. PMID- 8009159 TI - [Schizophrenia. What do families know?]. PMID- 8009161 TI - [The healthful applications of hydrotherapy]. PMID- 8009162 TI - [Health, sexuality and nursing]. PMID- 8009163 TI - [The professional nursing reserve. A quantitative analysis in the province of Barcelona]. PMID- 8009164 TI - [Fluorine in caries prevention]. PMID- 8009165 TI - [The fiber optic Swan-Ganz catheter. The monitoring of SvO2]. PMID- 8009166 TI - [Dairy products]. PMID- 8009167 TI - [Continuing education. 87. Maternal-child. The newborn infants of drug-dependent mothers]. PMID- 8009168 TI - [The catalog]. PMID- 8009169 TI - The lineage relationship of dendritic cells with other haematopoietic cells. AB - The lineage relationship of dendritic cells with other haematopoietic cells and within the broader class of dendritic cells is not well understood. Dendritic cells in different tissue sites and having slightly different characteristics all play a specialized role in maintaining self tolerance by the endocytosis and presentation of antigens within their environment. Recent evidence now suggests a possible lineage relationship between T cells and lymphoid dendritic cells and appears to conflict with the view that dendritic cells have a common origin with myeloid cells. One possibility is that dendritic cells mature in different tissue sites from bone marrow-derived precursors and develop region-specific characteristics which could reflect lineage differences. PMID- 8009170 TI - Biological function of the extracellular domain of the T-cell receptor constant region. PMID- 8009171 TI - Analysis of Oct2-isoform expression in lipopolysaccharide-stimulated B lymphocytes. AB - Oct2-isoform expression in splenic B cells stimulated with lipopolysaccharide or lipopolysaccharide plus phorbol-di-butyrate was analysed by cDNA cloning. The frequency of Oct2-positive clones was 1/15,000 in both libraries. Two new isoforms were found that generate novel amino- or carboxy-terminal sequences. An isoform lacking exon 11 destroyed the carboxy-terminal leucin-zipper region and introduced a frame shift creating a novel, proline-rich carboxy terminus. A new exon containing a highly basic region (4c) was characterized, between exons 4 and 5. This exon was inserted between glutamine-rich regions 2 and 3, carboxy terminal of a tentative leucine-zipper structure. In addition, a new combination isoform containing Oct2a's amino terminal insert (exon 7a) and Oct2b's carboxy terminal insert (exon 13) was found that created a novel large isoform, Oct2ab. More frequent use of the classical Oct2a and Oct2b isoforms was observed in the lipopolysaccharide-stimulated B cells, while a preference for the Oct2ab and Oct2ba isoforms was observed in lipopolysaccharide plus phorbol-di-butyrate treated cells. PMID- 8009172 TI - Indirect effects of oral tolerance in mice. AB - Anti-DNP antibody formation resulting from intraperitoneal (i.p.) immunization with DNP-KLH may be blocked by simultaneous (i.p.) injection of DNP-Ova or native Ova in mice orally tolerant to Ova, but not in normal mice. In Ova-tolerant mice the inhibition of anti-DNP antibody formation also occurred when DNP-Ova and DNP KLH were given by separate routes of immunization: subcutaneous (s.c.) and i.p. A second exposure to Ova by gastric intubation (gavage) or intravenous administration simultaneously with i.p. immunization with DNP-KLH failed to inhibit anti-DNP antibody formation. There was inhibition of responses to DNP-KLH i.p. by DNP-Ova given 24 h before, but not 24 h after, and in the Ova-tolerant mice, addition of DNP-Ova only to the primary immunization with DNP-KLH inhibited secondary and tertiary responses to DNP-KLH in the absence of further exposures to DNP-Ova. These results suggest that the indirect effects of parenteral exposure of tolerant mice to the tolerated immunogen may inhibit unrelated immune responses. This inhibition is not due to 'innocent bystanding' suppression, i.e., to inhibitory cytokines provided locally by specific suppressor lymphocytes; it may derive from more durable perturbations of immune system. PMID- 8009173 TI - T cells from the peripheral blood of coeliac disease patients recognize gluten antigens when presented by HLA-DR, -DQ, or -DP molecules. AB - Coeliac disease (CD) is a T-cell mediated immunological disease of the small intestine which is precipitated in susceptible individuals by ingestion of gluten. We recently reported that gliadin-specific T cells can be found in the small intestinal mucosa of CD patients, and that a preponderance of these T cells was restricted by the CD-associated DQ(alpha 1*0501,beta 1*0201) heterodimer. Here we report studies on whether the same is found for gliadin specific T cells in the peripheral blood of CD patients. T-cell responses towards gluten antigens in vitro were found for both most CD patients and healthy controls. Gluten specific T-cell clones (TCC) were established from four CD patients. Although a large proportion of these TCC were restricted by DQ molecules, including the CD associated DQ(alpha 1*0501,beta 1*0201) heterodimer, several were restricted instead by DR or DP molecules. Thus, gluten-derived peptides can be presented to T cells by several different HLA class-II molecules, and the preferential DQ(alpha 1*0501,beta 1*0201) restriction of gluten-specific T cells in the small intestinal mucosa of CD patients is less pronounced than for similar T cells in the peripheral blood. PMID- 8009174 TI - Opsonophagocytic activity induced by chimeric antibodies of the four human IgG subclasses with or without help from complement. AB - The opsonophagocytic activity of the four human IgG subclasses was studied using chimeric mouse-human antibodies with specificity for the hapten NIP. As target cells we used haptenized sheep red blood cells and N. meningitidis, labelled with different amounts of hapten. We used polymorphonuclear leucocytes (PMN) as effector cells to measure respiratory burst (RB), and U937 to measure phagocytosis/rosette formation. When the target cells were opsonized with antibody only, and PMN used as effector cells, IgG3 was highly efficient, while IgG1 revealed an intermediate activity and IgG2 and IgG4 were negative. The same pattern among the subclasses was obtained in the presence of complement source, when target cells with low hapten concentration were used. However, at high epitope concentration on the target cells, in the presence of complement source, IgG2 was highly active, while IgG4 was still negative or only slightly positive. When U937 were used as effector cells and complement was omitted, IgG1, IgG3 and IgG4 all revealed high phagocytic/rosette-forming activity, while IgG2 was negative. When the target cells were opsonized with antibody and complement, the phagocytic/rosette-forming activity was often suppressed. Our results reveal that all four human IgG subclasses possess opsonophagocytic capacity, but with different requirements concerning complement and Fc gamma Rs. They also enlighten us as to how IgG2 might perform its protective effect against harmful bacteria displaying high density of carbohydrate epitopes on their outside surface. PMID- 8009175 TI - Mycobacteria precipitate autoimmune rheumatic disease in NOD mice via an adjuvant like activity. AB - NOD mice spontaneously develop organ-specific autoimmunity and are widely used as a model for diabetes. NOD mice also exhibit some features of non-organ specific autoimmune rheumatic disease such as thymocytotoxic and anti-nuclear autoantibodies and they develop haemolytic anaemia in senescence. A single dose of 2.6 x 10(7) heat-killed Bacillus Calmette-Guerin (BCG) i.v. in 8-week-old NOD mice prevented diabetes but precipitated a syndrome similar to systemic lupus erythematosus (SLE), in which treated mice rapidly developed haemolytic anaemia, high titre anti-DNA and anti-Sm antinuclear autoantibodies, perivascular lymphocytic infiltration in the kidneys and glomerular immune complex deposition. Here, we examined the mechanism of action by which BCG precipitated rheumatic autoimmune disease in NOD mice. Two weeks after injection, reticuloendothelial cell function was dramatically increased in BCG-treated NOD mice. By 4 weeks, treated mice had a three- to four-fold increase in Mac-1+ and class-II+, B220 negative splenocytes and in vitro antigen-presentation capacity was enhanced two- to four-fold. In vivo responses to SRBC confirmed enhancement of DTH 4 weeks after BCG injection, consistent with an adjuvant-like activity. PMID- 8009176 TI - Binding of ras oncogene peptides to purified HLA-DQ(alpha 1*0102,beta 1*0602) and -DR(alpha,beta 1*0101) molecules. AB - Mutated oncogene peptides may be presented to T cells by HLA molecules. To be able to design the optimal peptides for stimulation of T cells in individuals with different HLA molecules, it is important to analyse the binding characteristics of oncogene peptides to HLA. HLA-DQ6 (DQ(alpha 1*0102,beta 1*0602)) and HLA-DR1 (DR(alpha,beta 1*0101)) molecules were purified from lysates of homozygous EBV-transformed cell lines. Purified HLA molecules were then tested for their ability to bind synthetic peptides in gel filtration assays. A p21 ras oncogene peptide (previously found to stimulate DQ6-restricted T-cell clones) and an influenza matrix peptide were labelled with 125I and served as indicator peptides for binding to DQ6 and DR1 respectively. Binding of homologous truncated and mutated p21 ras peptides and unrelated peptides was then evaluated by their capacity to inhibit binding of the indicator peptides. p21 ras-derived peptides were found to bind to both DQ6 and DR1 molecules indicating the existence of a promiscuous binding motif in these peptides. The binding affinities seemed to vary between the different peptides, but the amino acid substitutions resulting from natural mutations were not critical for binding. Notably, the results obtained for DQ6 in the biochemical peptide binding assay correlated well with results obtained in a functional assay using T-cell clones as probes. PMID- 8009177 TI - Mycobacterial heat-shock protein 65 induces proinflammatory cytokines but does not activate human mononuclear phagocytes. AB - The 65 kDa heat-shock protein (Hsp65), a well-conserved and immunodominant antigen which elicits a cellular and humoral immune response, may play a role in host defence against invading microorganisms and autoimmune disorders. The aim of the present study was to assess the effects of Hsp65 on the functional activities of human mononuclear phagocytes in the absence of lymphocytes. Incubation with Hsp65 resulted in an enhanced release of TNF-alpha and IL-1 beta by human monocytes and monocyte-derived macrophages (MDM). The amount of cytokines released by these cells in response to Hsp65 was similar to that released in response to IFN-gamma together with LPS. Incubation with ovalbumin did not stimulate the release of these cytokines. In vitro stimulation of monocytes with Hsp65 enhanced the membrane expression of complement receptor III but did not influence either the expression of Fc gamma-receptor I and HLA class-II antigens or the release of reactive oxygen intermediates. Therefore, Hsp65-stimulated monocytes cannot be considered to be activated according to classical criteria. The release of the proinflammatory cytokines TNF-alpha and IL-1 beta by human mononuclear phagocytes in response to Hsp65 indicates that this protein can contribute to both host defence and tissue damage in inflammatory lesions characterized by an abundant expression of Hsp65. PMID- 8009178 TI - Implanted solid human tumours grow under the renal capsule of cyclosporin immunosuppressed rats. AB - Cyclosporin (CsA) is a potent immunosuppressive drug widely used in organ transplantation. We transplanted fresh surgical samples from human solid malignant tumours into 45 CsA-immunosuppressed rats. Eight out of nine tumour types grew and remained viable for 5 weeks or more in at least two of the transplanted rats. In 29 rats (64%) a distinct growth of primary human tumours was recorded. Five malignancies (intestinal-type gastric carcinoma, adenocarcinoma of the lung, lymph node metastasis of a testicular teratocarcinoma, soft tissue malignant fibrous histiocytoma (MFH), and small-cell sarcoma) showed invasive and progressive growth. In all five cases the largest tumours were 0.9 cm or over in diameter when the rats were killed 5-9 weeks after transplantation. In three cases (adenocarcinoma of the colon, hypernephroma, and a second MFH) the growth of the implants under the kidney capsule was slow, but small living tumour transplants were still found 3-6 weeks later. In every case the microscopic morphology of the xenograft tumour was identical with the original tumour. In two cases the primary xenografts (teratocarcinoma and small cell sarcoma) were retransplanted into 11 CsA-immunosuppressed rats. In both types the second passage tumours grew, and the take-off and growth rates were comparable to the primary xenografts. Cyclosporin-treated laboratory rats are an alternative to immunodeficient nude and SCID mice for growing fresh human tumour transplants in vivo. Although a few infections were encountered, most of the rats survived the CsA treatment well for up to 2 months. PMID- 8009179 TI - In vivo study of mIgM and mIgD cross-linking on murine B cells. AB - In this study, we have analysed in mice the effects on the immune response of in vivo treatment with different rat monoclonal antibodies (MoAb) against IgM and IgD. Although the effects of IgD cross-linking have been studied already, no attempt has been made to characterize the effects of in vivo IgM crosslinking, probably because of the higher IgM serum levels compared to IgD. We have used a panel of nine monoclonal rat anti-mouse IgM and three anti-IgD antibodies and we have characterized their isotypes, avidities, immunoglobulin (Ig) cross-linking and internalization abilities. Our results show that injection of mice with some rat MoAb against IgM led to an important decrease of IgM serum level and internalization of membrane IgM (mIgM) on almost all B cells. Similarly, treatment with a high-avidity anti-IgD antibody induced disapperance of mIgD on B cells. Treatment with rat MoAb against IgM or IgD led to a synthesis of specific antibodies and there was a direct relationship between the Ig internalization abilities of rat MoAb and the induction of specific antibody production. Finally, treatment with a high-avidity rat MoAb against IgD induced a polyclonal IgE and IgG1 secretion. The significance of these results on mIg receptor functions is discussed. PMID- 8009180 TI - Voiding frequency, volumes and intervals in healthy schoolchildren. AB - To study the micturition pattern in healthy schoolchildren, 242 children aged 7 15, who all considered themselves healthy, completed a frequency/volume chart for 24 hours. Bed-wetting occurred in 21 (8.7%) and daytime incontinence in 19 (7.9%) children. Both symptoms occurred in four subjects, all girls. The incontinent children were excluded, leaving 206 subjects in the study. The healthy children voided 2-10 times a day, with 95% having a voiding frequency of 3-8. Twenty-three (11.2%) voided once during the night. All volume parameters varied greatly, both interindividually and intraindividually, independently of sex but weakly correlated to age and body parameters. The morning voiding was the largest, while the last before bedtime was the smallest. The interval between two voidings was longest in the morning decreasing towards the evening. The healthy child has a great ability to adapt the micturition pattern to social activities, which mean "to be the Boss of the Bladder". PMID- 8009181 TI - Translabial ultrasonography with pulsed colour-Doppler in the diagnosis of female urethral diverticula. AB - Urethral diverticulum in female can be easy to detect by physical examination but sometimes the diagnosis can be difficult. The classical radiographic diagnosis has traditionally been based on urethrography. Ultrasonographic approach is gaining more acceptance for the diagnosis of female diverticula. Transabdominal (1977), transrectal, transperineal and transvaginal techniques were described earlier. We here present a new and improved technique: i.e. the translabial ultrasonographic approach in combination with pulsed colour-doppler examination. An endovaginal 5 MHz probe was used. The transducer was placed directly against labia minora and the urethral orifice. The character of the diverticula and it's spatial relationship to the urethra could be described in 5 women. There was no need for other radiological examination preoperatively. The advantages of translabial sonographic technique are absence of ionizing radiation, reduced risk of infection, noninvasivity and comfortability. It is also a quick and reliable technique. PMID- 8009182 TI - Lethal cytomegalovirus adrenalitis in a case of AIDS. AB - The clinico-pathologic report of a case of cytomegalovirus (CMV) necrotizing adrenalitis arising in an intravenous drug-abuser and HIV-infected young is presented. CMV urinary tract infection, genital Kaposi's, and demyelinating changes in central nervous system were associated findings. PMID- 8009183 TI - Sodium thiosulphate in the treatment of renal tubular acidosis I with nephrocalcinosis. AB - Nephrocalcinosis is a common feature in renal tubular acidosis I (RTA-I) and contributes to renal insufficiency. We describe a patient, 37 years old, with RTA I, mild renal failure and extended nephrocalcinosis. His disease was diagnosed in age 28 and patient is under treatment with sodium bicarbonate, potassium gluconate and sodium thiosulphate for 9 years. By this treatment nephrocalcinosis and renal function have not been worsened and patient is without clinical symptoms. PMID- 8009184 TI - Management of renal stab wounds by arteriographic embolisation. AB - A 26 year old man was admitted with multiple stab wounds to his chest, abdomen and right loin. He was noted to have a large haemothorax, a tender abdomen and frank haematuria. At laparotomy, there was a small non expanding retroperitoneal haematoma that was not explored, and no visceral damage. Post operatively he continued to have haematuria. IVP and ultrasound showed perirenal haematoma and clot in the upper pole calyces but was otherwise normal. Renal arteriography demonstrated a pseudo-aneurysm in the right mid region, feeding an arteriovenous fistula (Figure 1). Selective renal artery embolisation with spring occlusion coils was performed which occluded the branch supplying the false aneurysm and fistula (Figure 2). He had no further haematuria. At six month follow up he remained well, normotensive and with no haematuria. Isotope renogram showed 30% loss of function at the upper pole. PMID- 8009185 TI - Adhesion of the labia minora (female phimosis or urocolpos) in the elderly. PMID- 8009186 TI - Urine protein excretion after Hymenoptera sting. AB - The urinary excretion of albumin was measured on 7 consecutive days after a bee or wasp sting in 20 healthy persons, using a semiquantitative immunochemical chromatographic procedure (Micral stick). The mean albumin excretion was 11.1 +/- 15.0 (SD) mg/l. This was not significantly different from the findings in a control group of 17 volunteers with no history of bee or wasp sting (mean 8.7 +/- 17.4 mg/l). Pathologic albumin excretion (50-100 mg/l) was found in three of the sting group, with mean 37.2 +/- 23.7 mg/l. After 2 more months the urinary albumin excretion had normalized in two of the three, with mean 19.3 +/- 16.0 mg/l. Nephrotic syndrome did not occur. Reactions to the sting corresponded to 1 4 on the Muller scale, but were not correlated to albumin excretion. PMID- 8009187 TI - Early renal graft function in recipients treated with the calcium channel blocker felodipine. AB - Calcium channel blocking agents (CCB) differ in molecular structure and effects. Each must therefore be evaluated separately. Out of 139 patients who received cadaveric kidney transplants between March 1990 and December 1991 22 were treated with the CCB agent felodipine as antihypertensive therapy on admission and post transplant. The early function of their grafts was compared with that of grafts to patients not treated with any CCB agent pre or post transplant (n = 38). There were no other significant differences in patient or donor characteristics. In the felodipine treated group, 18/22 showed immediate onset of graft function vs 20/38 in the non CCB group (p = 0.02). Dialysis post transplant was required by one felodipine-treated patient vs 12 in the non CCB group. Serum creatinine on day 7 was lower in felodipine treated patients, median 155 vs 259 mumol/l. Felodipine treatment did not seem to cause any significant interaction with cyclosporin A (CyA). The frequency and severity of acute rejection did not differ between the groups. PMID- 8009188 TI - Sequential changes in vitamin D and calcium metabolism after successful renal transplantation. AB - A prospective study was made of sequential changes in the metabolism of vitamin D and calcium in 19 allograft recipient during the first year after successful renal transplantation. All but one of the patients received cyclosporine A combined with corticosteroids and azathioprine as immunosuppressive therapy. Shortly after transplantation most patients showed transient hypocalcemia and hypophosphatemia. At the time of transplantation 17 of 19 patients had an elevated plasma intact parathyroid hormone (PTH) level, and at the close of follow-up one in four patients. In six other patients intact PTH was within the reference range, but high in relation to simultaneously measured serum ionized calcium. According, one year after transplantation less than half of the patients showed complete resolution of hyperparathyroidism. The change towards normal in the metabolism of vitamin D began within the first post-transplantation week irrespective of the onset of diuresis. One to two weeks after transplantation 1,25(OH)2D3 and 24,25(OH)2D3 reached the lower limit of normal range. In these renal allograft recipients who received cyclosporine A the long-term values of serum 1,25(OH)2D3 did not differ from those of normal subjects. PMID- 8009189 TI - Superselective transarterial embolization of renal arteriovenous malformations of cryptogenic origin. AB - Renal arteriovenous (AV) shunts of unknown origin are rare clinical findings. When symptomatic they can as other renal AV shunts and malformations cause hypertension, congestive heart failure and hematuria. During the last few years the treatment has tended to go from surgery to the more gentle and renal parenchyma sparing but yet effective endovacular embolization techniques. Two cases of renal vascular malformations with severe clinical symptoms necessitating treatment are presented. Treatment was successfully performed with tissue adhesive and coils. PMID- 8009190 TI - Significance of simple renal cysts and percutaneous cyst puncture on renal function. AB - Renal function was investigated in 17 patients with simple renal cysts. Single kidney glomerular filtration rate was estimated by gamma camera renography with 99mTc-DTPA before, 5 days and 6 months after percutaneous puncture and evacuation of the cysts. Prior to the puncture and evacuation, the only negative effects on renal function noted were signs of moderate obstruction of the renal outflow in 2 patients. Percutaneous puncture with evacuation of the cystic fluid did not change the renal function significantly. It was concluded that simple renal cysts do not have any functional consequences nor does percutaneous puncture and evacuation of the cysts. PMID- 8009191 TI - Interpleural analgesia for postoperative pain relief in renal surgery patients. AB - The feasibility of interpleural analgesia for postoperative pain relief after renal surgery using anterior intercostal incision was studied in 16 adult patients. 20 ml bupivacaine plain 5 mg/ml in ten patients, and the same dose of bupivacaine with epinephrine 5 micrograms/ml in six patients, was injected through epidural catheter into the pleural space of the operated side, maximally three times per 24 hours. As additional pain medication, oxycodone i.m. was given if needed. In ten control patients, oxycodone was the only pain medication. Postoperative pain relief in patients who received interpleural bupivacaine plain was excellent in four, moderate in four and poor in two cases. For supplemental pain relief the patients were given 2.1 +/- 1.1 (SEM) injections of oxycodone during the three days. Control patients received, respectively. 11.6 +/- 0.7 injections of oxycodone, and they considered the pain relief excellent in six and moderate in four cases. Median duration of interpleural analgesia was in bupivacaine plain cases 6 h (range 2-14 h) and in bupivacaine with epinephrine 7 h (range 4-15 h). The mean peak serum concentration of bupivacaine plain was 1868 +/- 168 ng/ml, and that of bupivacaine with epinephrine 1312 +/- 273 ng/ml. No complications were seen. The results suggest that interpleural analgesia obtained by 20 ml bupivacaine 5 mg/ml three times a day gives most patients good pain relief. PMID- 8009192 TI - Stripping of the distal ureter in association with nephroureterectomy. Evaluation of the method. AB - Nephroureterectomy is the standard treatment for transitional cell tumours of the renal pelvis. A single-incision surgical technique with use of a vein stripper to remove the distal ureter is evaluated. The method proved to be safe. There was no evidence of increased immediate or long-term risks, including extravesical recurrence of tumour. The method can be recommended for patients with renal pelvic papilloma and probably also for tumours in the upper part of the ureter, but should not be used when there is tumour in the distal ureter. PMID- 8009194 TI - 'Clam' ileocystoplasty. AB - 'Clam' enterocystoplasty has been performed in 23 patients in the treatment of lower urinary tract dysfunction. Twenty patients had neurogenic disorder while three were neurologically normal. Patients were evaluated urodynamically pre- and postoperatively. A significant change from a high pressure bladder to a low pressure bladder was found. Most patients had detrusor instability/hyperreflexia but 7 were operated due to poor bladder compliance. Only 2 patients had postoperative detrusor instability. Three patients later had a urinary diversion. Nineteen patients became dry giving a total success rate of 87% although 14 had to do clean intermittent self catheterization. PMID- 8009193 TI - The application of the modified rectal bladder in management of the compromized urethral damage. AB - Failure to repair the traumatic injuries of the lower urinary tract with loss of urethral sphincteric function usually puts forward the subject of urinary diversion. Ten males and five females presented with extensive urethral damage and with or without vesical fistulas. All attempts of repair were exhausted before the decision of diversion was planned. Continent urinary diversion using the modified rectal bladder (the augmented and valved rectum) was utilized. The procedure entailed functional isolation of the rectum without terminal colostomy and depended on colorectal intussuscepted valve. All the patients are currently evaluated with follow up periods ranging 10-56 months. Evidences proved the effectiveness of the colorectal valve in providing non impeded fecal stream to the functionally isolated rectal reservoir. Continent status is attributed to the ileal patching that produces a low pressure reservoir against the effective high anal resistance. The results support the distinct superiority of the modified rectal bladder to either the conventional methods of urinary diversion to the rectum or the abdominal reservoir with continent catheterizable stomas. PMID- 8009195 TI - Pre- and postoperative DNA ploidy patterns correlated to pT-stage, histological grade and tumour volume in total prostatectomy specimens. AB - Fifty-four consecutive patients with a preoperative diagnosis of localized prostatic cancer underwent total retropubic prostatectomy. The specimens were step-sectioned at 5 mm intervals. Volumes of invasive cancer (IC) and prostatic intraepithelial neoplasia (PIN) were calculated by computerized planimetry. From preoperative core and fine needle aspiration biopsies and from each prostatectomy specimen, multiple samples were taken from IC and PIN areas for DNA ploidy analysis. The study aimed to evaluate current biopsy sampling techniques as regards their suitability for DNA analysis and to assess the heterogeneity of DNA ploidy and correlate the latter to postoperative pT-stage and tumour volume. When compared with the prostatectomy specimens, the preoperative assessment of non diploid DNA patterns in biopsies had a sensitivity of 62% and a specificity of 86%. Samples from 24 surgical specimens contained non-diploid DNA in the main tumour and in one or several of the satellites. However, all these cases also contained diploid cell lines, both in the main tumour and in one or several of the satellites. Tumours with a volume exceeding 12 cc:s were non-diploid in 87.5% of cases (7/8). Tumours with volumes between 8 and 12 cc:s contained non-diploid foci in 50% of cases (2/4). Tumours smaller than 2 cc:s were non-diploid in 18% of cases (2/11). All non-diploid tumours were moderately or poorly differentiated. Of the non-diploid tumours, 96% (23/24) displayed capsular penetration versus 57% (17/30) of the diploid tumours (p < 0.0001). All PIN samples were made up of diploid cell lines.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8009196 TI - Testicular histology after treatment with the new antiandrogen Casodex for carcinoma of the prostate. A preliminary report. AB - Five men aged 55-78 years, had received Casodex 50 mg p.o. daily for seven to 12 months. Because of tumour progression orchiectomy was performed. All testes were examined with light- and electronmicroscopy. Evidence of Leydig cell hyperplasia was present in testes from three patients. However, the ultrastructural appearance of the Leydig cells was normal. The spermatogenesis was reduced in all testes, although not significantly different from controls. We believe the Leydig cell hyperplasia reflects an increased proliferative stimulation by luteinizing hormone or a direct effect of Casodex. PMID- 8009197 TI - Reproducibility of instruments designed to measure subjective evaluation of female stress urinary incontinence. AB - The aim of this study was to construct two instruments by which detailed knowledge of women's problems related to stress urinary incontinence (SUI) could be registered, and to test the reproducibility of the results obtained. Fourteen women with urodynamically proven SUI, and a mean age of 42.8 years (range 18-56) participated in the study. The leakage index was a five point scale (1 = never, 5 = always) containing thirteen types of physical exertions known to trigger urinary leakage. The social activity index contains nine social settings in which women may have problems to participate. For each parameter a 10 cm visual analogue scale (0 = impossible to participate, 10 = no problem to participate) was used for registration. The correlation coefficient for test 1 and 2 was .92 (p < 0.01) and .94 (p < 0.01) for the leakage and the social activity index, respectively. The results obtained were reproducible, and the instruments gave detailed information about how women perceived SUI. PMID- 8009198 TI - A new twist in the tale of nature's asymmetry. PMID- 8009199 TI - Progress in parasitology. PMID- 8009200 TI - Dioxin effects. PMID- 8009202 TI - Quantity no longer counts in Britain. PMID- 8009201 TI - AIDS vaccine research. U.S. panel votes to delay real-world vaccine trials. PMID- 8009203 TI - Misconduct panel sets ambitious agenda. PMID- 8009204 TI - Lucky break for kidney disease gene. PMID- 8009205 TI - A challenge to p16 gene as a major tumor suppressor. PMID- 8009206 TI - A new test gives early warning of a growing killer. PMID- 8009207 TI - Genome initiatives tackle developing world's big killers. PMID- 8009208 TI - Parasitology. PMID- 8009209 TI - Fighting parasites on a shoestring. PMID- 8009210 TI - Finding 'sustainable' ways to prevent parasitic diseases. PMID- 8009211 TI - Models aid understanding, help control parasites. PMID- 8009212 TI - Fighting the parasites of poverty: public research, private industry, and tropical diseases. PMID- 8009213 TI - Economics and the argument for parasitic disease control. PMID- 8009214 TI - RNA editing and the evolution of parasites. PMID- 8009215 TI - Vector biology and the control of malaria in Africa. PMID- 8009216 TI - Immunoglobulin E and effector cells in schistosomiasis. PMID- 8009217 TI - Malaria pathogenesis. AB - Malaria is a disease caused by repeated cycles of growth of the parasite Plasmodium in the erythrocyte. Various cellular and molecular strategies allow the parasite to evade the human immune response for many cycles of parasite multiplication. Under certain circumstances Plasmodium infection causes severe anemia or cerebral malaria; the expression of disease is influenced by both parasite and host factors, as exemplified by the exacerbation of disease during pregnancy. This article provides an overview of malaria pathogenesis, synthesizing the recent field, laboratory, and epidemiological data that will lead to the development of strategies to reduce mortality and morbidity. PMID- 8009218 TI - Mathematical studies of parasitic infection and immunity. AB - The techniques that underpin modern molecular biology have been rapidly adopted by those interested in the major parasitic infections of humans. The parasitological literature is full of reports of genes and their amino acid sequences, of molecules, of cell membrane receptors and channels, and of the fine details of the immunological responses mounted by the host to combat infection. Much less enthusiasm has been shown for the mathematical techniques that facilitate the analysis and interpretation of dynamical processes such as transmission, evolution, and the interplay between parasite population growth and immunological responses within the host. Molecular techniques provide enormous opportunities for description, but ultimately, understanding biological systems with the precision that physicists and engineers aspire to in their own fields will require quantitative description of the many rate processes that dictate both an observed pattern and the dynamics of its change. PMID- 8009219 TI - Low-barrier hydrogen bonds and enzymic catalysis. AB - Formation of a short (less than 2.5 angstroms), very strong, low-barrier hydrogen bond in the transition state, or in an enzyme-intermediate complex, can be an important contribution to enzymic catalysis. Formation of such a bond can supply 10 to 20 kilocalories per mole and thus facilitate difficult reactions such as enolization of carboxylate groups. Because low-barrier hydrogen bonds form only when the pKa's (negative logarithm of the acid constant) of the oxygens or nitrogens sharing the hydrogen are similar, a weak hydrogen bond in the enzyme substrate complex in which the pKa's do not match can become a strong, low barrier one if the pKa's become matched in the transition state or enzyme intermediate complex. Several examples of enzymatic reactions that appear to use this principle are presented. PMID- 8009220 TI - African Homo erectus: old radiometric ages and young Oldowan assemblages in the Middle Awash Valley, Ethiopia. AB - Fossils and artifacts recovered from the middle Awash Valley of Ethiopia's Afar depression sample the Middle Pleistocene transition from Homo erectus to Homo sapiens. Ar/Ar ages, biostratigraphy, and tephrachronology from this area indicate that the Pleistocene Bodo hominid cranium and newer specimens are approximately 0.6 million years old. Only Oldowan chopper and flake assemblages are present in the lower stratigraphic units, but Acheulean bifacial artifacts are consistently prevalent and widespread in directly overlying deposits. This technological transition is related to a shift in sedimentary regime, supporting the hypothesis that Middle Pleistocene Oldowan assemblages represent a behavioral facies of the Acheulean industrial complex. PMID- 8009221 TI - Functional role of type I and type II interferons in antiviral defense. AB - Mice lacking the known subunit of the type I interferon (IFN) receptor were completely unresponsive to type I IFNs, suggesting that this receptor chain is essential for type I IFN-mediated signal transduction. These mice showed no overt anomalies but were unable to cope with viral infections, despite otherwise normal immune responses. Comparison of mice lacking either type I or type II IFN receptors showed that, at least in response to some viruses, both IFN systems are essential for antiviral defense and are functionally nonredundant. PMID- 8009222 TI - Involvement of the IRF-1 transcription factor in antiviral responses to interferons. AB - The mechanisms underlying interferon (IFN)-induced antiviral states are not well understood. Interferon regulatory factor-1 (IRF-1) is an IFN-inducible transcriptional activator, whereas IRF-2 suppresses IRF-1 action. The inhibition of encephalomyocarditis virus (EMCV) replication by IFN-alpha and especially by IFN-gamma was impaired in cells from mice with a null mutation in the IRF-1 gene (IRF-1-/- mice). The IRF-1-/- mice were less resistant than normal mice to EMCV infection, as revealed by accelerated mortality and a larger virus titer in target organs. The absence of IRF-1 did not clearly affect replication of two other types of viruses. Thus, IRF-1 is necessary for the antiviral action of IFNs against some viruses, but IFNs activate multiple activation pathways through diverse target genes to induce the antiviral state. PMID- 8009223 TI - Expanding the scope of RNA catalysis. AB - The basic notions of transition state theory have been exploited in the past to generate highly selective catalysts from the vast library of antibody molecules in the immune system. These same ideas were used to isolate an RNA molecule, from a large library of RNAs, that catalyzes the isomerization of a bridged biphenyl. The RNA-catalyzed reaction displays Michaelis-Menten kinetics with a catalytic rate constant (kcat) of 2.8 x 10(-5) per minute and a Michaelis constant (Km) of 542 microM; the reaction is competitively inhibited by the planar transition state analog with an inhibition constant (Ki) value of approximately 7 microM. This approach may provide a general strategy for expanding the scope of RNA catalysis beyond those reactions in which the substrates are nucleic acids or nucleic acid derivatives. PMID- 8009224 TI - Maternal rescue of transforming growth factor-beta 1 null mice. AB - Maternal sources of transforming growth factor-beta 1 (TGF-beta 1) are shown here to contribute to the normal appearance and perinatal survival of TGF-beta 1 null newborn mice. Labeled TGF-beta 1 crossed the placenta and was recovered intact from various tissues after oral administration to mouse pups. TGF beta-1 protein was also detected in cells recovered from breast milk. In immunohistochemical analyses, TGF-beta 1 null embryos and null newborn pups born to TGF-beta 1 heterozygotes stained positive for TGF-beta 1, whereas those born to a null female were negative and had severe cardiac abnormalities. These results suggest an important role for maternal sources of TGF-beta 1 during development and, more generally, provide evidence for maternal rescue of targeted gene disruption in the fetus. PMID- 8009225 TI - Implications of FRA16A structure for the mechanism of chromosomal fragile site genesis. AB - Fragile sites are chemically induced nonstaining gaps in chromosomes. Different fragile sites vary in frequency in the population and in the chemistry of their induction. DNA sequences encompassing and including the rare, autosomal, folate sensitive fragile site, FRA16A, were isolated by positional cloning. The molecular basis of FRA16A was found to be expansion of a normally polymorphic p(CCG)n repeat. This repeat was adjacent to a CpG island that was methylated in fragile site-expressing individuals. The FRA16A locus in individuals who do not express the fragile site is not a site of DNA methylation (imprinting), which suggests that the methylation associated with fragile sites may be a consequence and not a cause of their genesis. PMID- 8009227 TI - Structure of the RGD protein decorsin: conserved motif and distinct function in leech proteins that affect blood clotting. AB - The structure of the leech protein decorsin, a potent 39-residue antagonist of glycoprotein IIb-IIIa and inhibitor of platelet aggregation, was determined by nuclear magnetic resonance. In contrast to other disintegrins, the Arg-Gly-Asp (RGD)-containing region of decorsin is well defined. The three-dimensional structure of decorsin is similar to that of hirudin, an anticoagulant leech protein that potently inhibits thrombin. Amino acid sequence comparisons suggest that ornatin, another glycoprotein IIb-IIIa antagonist, and antistasin, a potent Factor Xa inhibitor and anticoagulant found in leeches, share the same structural motif. Although decorsin, hirudin, and antistasin all affect the blood clotting process and appear similar in structure, their mechanisms of action and epitopes important for binding to their respective targets are distinct. PMID- 8009228 TI - Paget's disease of bone: classical pathology and electron microscopy. PMID- 8009226 TI - Receptor and ligand domains for invasion of erythrocytes by Plasmodium falciparum. AB - A 175-kilodalton erythrocyte binding protein, EBA-175, of the parasite Plasmodium falciparum mediates the invasion of erythrocytes. The erythrocyte receptor for EBA-175 is dependent on sialic acid. The domain of EBA-175 that binds erythrocytes was identified as region II with the use of truncated portions of EBA-175 expressed on COS cells. Region II, which contains a cysteine-rich motif, and native EBA-175 bind specifically to glycophorin A, but not to glycophorin B, on the erythrocyte membrane. Erythrocyte recognition of EBA-175 requires both sialic acid and the peptide backbone of glycophorin A. The identification of both the receptor and ligand domains may suggest rational designs for receptor blockade and vaccines. PMID- 8009229 TI - Bone histomorphometry and skeletal distribution of Paget's disease of bone. PMID- 8009230 TI - Epidemiological aspects of Paget's disease: family history and relationship to other medical conditions. AB - Some epidemiological aspects of Paget's disease were examined using questionnaires completed by 864 patients with physician-diagnosed Paget's disease and 500 controls of similar ages. Specifically studied were issues of familial aggregation of the disorder, history of exposure to certain infectious diseases, other medical disorders, and calcium intake (as assessed by milk consumption) in childhood. A history of Paget's disease in a first-degree relative was noted in 12% of patients and 2% of controls. Among patients, those with a positive family history had an earlier mean age at diagnosis and a greater prevalence of bone deformity than patients with a negative family history. The risk of a first degree relative of a pagetic patient developing Paget's disease was 7 times greater than the risk of an individual without such a relative, and the cumulative risk to age 90 for a first-degree relative of a patient was 9%, compared with a 2% risk in a person without affected relatives. The risk to the relative was greatest if the patient had an age at diagnosis of less than 55 years and had deforming bone disease. There was no difference between patients and controls for a variety of viral infections, including measles, and no difference in ownership of dogs and possible exposure to canine viruses. Diabetes was more common in controls than in patients, but arthritis, skeletal fractures, primary hyperparathyroidism, osteoporosis, and thyroid disease (in women) and renal stones (in men) were reported more commonly by patients. Milk consumption during childhood and adolescence was lower in patients than in controls.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8009231 TI - Paget's disease: the South American experience. PMID- 8009232 TI - Some epidemiological aspects of Paget's disease of bone in Israel. PMID- 8009233 TI - HLA polymorphisms in Paget's disease of bone. PMID- 8009234 TI - Paramyxoviruses and their role in disease. PMID- 8009235 TI - Paramyxoviruses in Paget's disease. PMID- 8009237 TI - Biochemical and scintigraphic assessment of Paget's disease. PMID- 8009236 TI - Biology of the osteoclast in Paget's disease. PMID- 8009238 TI - Biochemical measurements in Paget's disease of bone. PMID- 8009239 TI - Response of biochemical markers of bone turnover to pamidronate infusion in Paget's disease of bone. PMID- 8009240 TI - Application of quantitative computed tomography to Paget's disease of bone. AB - Serial evaluation of pagetic lesions is handicapped by the inability of conventional methods to reproduce precisely the positioning of the area of interest. A computed tomography method that provides visual and quantitative comparisons between data sets acquired at different times has been developed. The utility of this method is illustrated with an example of serial examinations that demonstrate the effect of treatment on small lytic lesions in the lumbar spine. A further demonstration is made of the ability of this method to identify and quantify lytic changes within the cochlear capsule. PMID- 8009241 TI - Articular complications of Paget's disease of bone. AB - Articular symptoms in Paget's disease are very common. The most frequent cause of articular symptoms is OA, secondary to the Paget's disease. Radiographic OA due to Paget's disease is not always symptomatic, and periarticular Paget's disease does not invariably lead to OA. Intraarticular lidocaine occasionally is helpful in separating the symptoms of OA from those of Paget's disease. PMID- 8009243 TI - A review of corrective osteotomies for deformity in Paget's disease. AB - Corrective diaphyseal osteotomies for pagetic deformities may require a long time for union. However, metaphyseal osteotomies healed uneventfully. The use of plate fixation was associated with a lower rate of complications in diaphyseal osteotomies in Paget's disease. External fixation was associated with the highest rate of complications. Medical treatment did not seem to minimize blood loss or expedite union rate or time to union. PMID- 8009242 TI - Paget's disease of bone: orthopedic complications. AB - Orthopedic complications of Paget's disease are among the most common indications for treatment of Paget's disease. These complications include severe bone pain, joint pain, skeletal deformity, pathological fracture, and rarely malignant degeneration. The use of effective pharmacological modalities has transformed the treatment of Paget's disease in the past four decades. Although few patients with Paget's disease ever require surgical therapy, successful surgical management of severe orthopedic complications has improved the quality of life for many sufferers. Selected modalities with promising results include total hip replacement for intractable pagetic arthritis of the hip, proximal tibial osteotomy for painful malalignment of the knees, total knee replacement for intractable arthritis of the knee, and internal fixation for pathological fracture. Common surgical complications of joint replacement include infection, hemorrhage, heterotopic ossification, and aseptic loosening. The medical, surgical, and rehabilitation modalities available in managing primary and secondary orthopedic complications of Paget's disease provide a wide array of options that must be carefully considered in each patient. PMID- 8009244 TI - Treatment of Paget's disease--an overview. PMID- 8009245 TI - Calcitonin: history and prospects--a personal view. PMID- 8009246 TI - Bisphosphonates: pharmacology. PMID- 8009247 TI - Pamidronate stimulates recruitment and decreases longevity of osteoclast nuclei in mice. PMID- 8009248 TI - Strategies of treatment of Paget's disease with bisphosphonates. PMID- 8009249 TI - Dramatic response to plicamycin in a patient with severe Paget's disease refractory to calcitonin and pamidronate. PMID- 8009250 TI - Treatment of patients with advanced Paget's disease of bone with two cycles of gallium nitrate. PMID- 8009251 TI - Effects of intravenous dichloromethylene bisphosphonate (CL2MBP) in the treatment of Paget's disease of bone. PMID- 8009252 TI - Assessment of optimum duration of therapy with oral dichloromethylene diphosphonate (clodronate) in the treatment of Paget's disease. PMID- 8009253 TI - Risedronate in Paget's disease: preliminary results of a multicenter study. PMID- 8009254 TI - Intravenous pamidronate: evolution of an effective treatment strategy. PMID- 8009256 TI - Use of the bisphosphonate space in treatment and retreatment of Paget's disease. PMID- 8009255 TI - Single-day intravenous pamidronate in Paget's disease. AB - Although the efficacy of pamidronate (APD) in Paget's disease is established, the optimal dose and regimen are not known. In this article, further findings using a single-day intravenous infusion are reported, comparing the responses of 114 subjects treated with doses of 20 mg (n = 35), 30 mg (n = 26), 45 mg (n = 29), and 60 mg (n = 24). Assessments of clinical and biochemical response were made at 2, 4, 8, 12, and 24 weeks. Patients with persistent disease activity were retreated after 24 weeks. The single-day infusion of APD was followed by a rapid and sustained biochemical response, but in only 24% of patients did alkaline phosphatase (AP) levels normalize. Of patients in whom the serum AP level normalized, 93% had initial values less than three times the upper limit of normal. Although there was no significant difference in response between the lower dosage groups, there was a greater response in patients treated with a higher dose of APD. The percentage decrease in AP from baseline was similar after the first and second infusions. These findings show that a single-day infusion of APD is effective in the treatment of Paget's disease and that a dose-response relationship exists. PMID- 8009257 TI - Moderate Paget's disease treated with pamidronate: comparison of various infusion rates for a 60-mg single dose. PMID- 8009258 TI - Response of 99mTc-MDP scanning and whole-body retention to intravenous pamidronate. PMID- 8009259 TI - Treatment of Paget's disease of bone with single-dose intravenous pamidronate. PMID- 8009260 TI - Intravenous aminopropylidene bisphosphonate in the treatment of severe polyostotic Paget's disease of bone. PMID- 8009261 TI - Long-term efficacy of intravenous pamidronate in Paget's disease of bone. PMID- 8009262 TI - Effect of pamidronate on indices of bone turnover in Paget's disease followed for 6 years. PMID- 8009263 TI - Intravenous pamidronate in Paget's disease--response is dependent on radiographic and biochemical severity. PMID- 8009264 TI - A pregnant lady with narrow complex tachycardia. PMID- 8009265 TI - Pregnancy in a patient receiving busulphan for chronic myeloid leukaemia. AB - A 33-year-old Malay lady with chronic myeloid leukaemia (CML) became amenorrhoeic during therapy with busulphan. Pregnancy was diagnosed via a urine pregnancy test and an ultrasound confirmed a viable foetus at 16 weeks. The busulphan was stopped. Her pregnancy was unremarkable and continued till term. She delivered a healthy child. PMID- 8009266 TI - Neonatal meningitis due to non-encapsulated Haemophilus influenzae in a set of twins--a case report. AB - A set of twins born to a 24-year-old primigravida had evidence of sepsis 24 to 60 hours after birth and were treated empirically with penicillin and gentamicin. A non-encapsulated H. influenzae biotype IV strain was isolated from the blood cultures of both and from the CSF of twin II. The isolates were beta-lactamase positive and hence showed resistance to ampicillin and therapy was changed to chloramphenicol only. Twin II recovered but Twin I developed a brain abscess in the left occipital region which resolved with extended antibiotic treatment. Although ampicillin-resistant H. influenzae have been reported in Malaysia, invasive disease by such strains are rare. PMID- 8009267 TI - A case of alkaptonuria with root canal stenosis. AB - Spinal involvement in alkaptonuria is common. Patients usually present in the third or fourth decade with spondylosis or acute intervertebral disc prolapse. Alkaptonuria with root canal stenosis has however hitherto not been reported. We wish to report one such patient. PMID- 8009268 TI - Primary closure following drainage of a rectus sheath muscle abscess. AB - The primary closure of a rectus sheath muscle abscess was performed on an 11-year old child following evacuation of its contents under antimicrobial cover. Complete healing was achieved in eight days. This method avoids the delays in wound healing and morbidity associated with conventional drainage and shortens convalescence. PMID- 8009269 TI - A fulminant case of neuroleptic malignant syndrome. AB - We report a fulminant case of Neuroleptic Malignant Syndrome in a 31-year-old male schizophrenic on haloperidol, thioridazine, benzhexol and flurazepam who presented with rigidity, fever, stupor and autonomic instability. He succumbed rapidly over 6 days to rhabdomyolysis, acute renal failure, status epilepticus and disseminated intravascular coagulopathy despite treatment with dantrolene and bromocriptine at the outset. PMID- 8009270 TI - Echocardiographic detection of mobile right atrial thrombus. AB - Mobile right atrial thrombus is a rare echocardiographic diagnosis with important implications on further management. We report a case of 50-year-old woman with deep vein thrombosis of her left lower limb, who was found to have a large mobile serpiginous right atrial thrombus on both two-dimensional echocardiography (2DE) and transoesophageal echocardiography (TEE). She developed acute pulmonary embolism within thirty-six hours of diagnosis and subsequently underwent successful pulmonary embolectomy. This case demonstrates the usefulness of echocardiography as a non-invasive tool in the investigation of suspected pulmonary thromboembolism. The detection of right atrial thrombus mandates serious consideration for prompt surgical action. PMID- 8009271 TI - Cancer: to tell or not to tell? PMID- 8009272 TI - Management of stroke. PMID- 8009273 TI - Postnatal depression. PMID- 8009274 TI - Postnatal depression in Singapore women. AB - A longitudinal study of depressive symptomatology in 200 postnatal women using the Edinburgh Postnatal Depressive Scale showed that depressive symptomatology is mild but present in nearly all the postpartum women; however only one per cent of the women over a 6-month period had scores suggestive of a postnatal depression. None had experienced any depressive hallucinations or delusions during this period. PMID- 8009275 TI - Radiofrequency catheter ablation of accessory pathways: the initial experience in Singapore. AB - Radiofrequency catheter ablation is a recently introduced non-surgical technique for curing patients with arrhythmias as a result of conduction over an accessory pathway in patients with the Wolff-Parkinson-White (WPW) syndrome. We present our initial experience with this technique. There were 90 patients (61 males, 29 females) with a mean age of 37 +/- 14.4 years (range: 13-73 years). All except one were symptomatic with a mean duration of symptoms of 10 +/- 9.4 years (range: 0.1-40 years). The indications for catheter ablation were failure of drug therapy in 71, patient's preference in 10, increased risk of sudden death in 6 and almost incessant tachycardia in 3. The radiofrequency ablation was performed using a deflectable 7 French 4 mm tip electrode catheter positioned at the mitral or tricuspid annulus. The site of the accessory pathway was localised by electrophysiological study and radiofrequency energy applied via the tip of the catheter. There were 100 accessory pathways as 10 (10%) patients had multiple accessory pathways. There were 69 (69%) left free wall, 11 (11%) posteroseptal, 13 (13%) right free wall, 6 (6%) right anteroseptal accessory pathways and one (1%) midseptal accessory pathways. Ninety-six percent (96%) of the accessory pathways were successfully ablated on the first ablation. Two of the 4 initially unsuccessful ablations were successfully reablated, giving an overall success rate of 98%. There were no major complications. In conclusion, radiofrequency catheter ablation of accessory pathways is highly successful and safe and provides a definitive cure for patients with the WPW syndrome.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8009276 TI - A study of needle-stick injuries among house officers in a major hospital. AB - House officers (HO) undergoing housemanship in the departments of Surgery, Medicine and Orthopaedics in a major hospital were studied with regard to the incidence and causes of needle-stick injuries via a self-administered recall questionnaire. A response rate of 79% (44 out of 56 HOs) was obtained, of which 35 HOs had completed 2 months of housemanship and 9 had completed 8 months. A total of 171 needle-stick injuries (1.2 per HO-month) were reported with 6 HOs never sustaining an injury. The more experienced HOs had less injuries than the less experienced HOs with an incidence rate of 4.65 (95% confidence interval of 4.08-8.87). Resheathing was the commonest reported cause of injury (45% of 113 described cases). Forty-three HOs (90%) reported that they frequently resheathed used needles before disposal. Most HOs (61%) felt that they were at nil to moderate risk of contracting an infectious disease from a needle-stick injury. A system of reporting and policies on management of infected personnel may be needed to monitor this health hazard. PMID- 8009277 TI - Continuous spinal analgesia--initial experiences with differential sensory block and labour pain relief. AB - This report describes the use of microcatheters to provide continuous spinal analgesia for the relief of labour pain. Bupivacaine 0.025% was administered through a 28G spinal microcatheter resulting in a differential block which provided effective labour pain relief. Conduction by the smaller pain fibres from the uterus were blocked, while relatively sparing the larger A fibres. Motor power, sense of touch, and discrimination between blunt and sharp objects were therefore left relatively intact. Patients were thus spared the discomfort of motor paralysis and an intense sensory block. No patient had hypotension (blood pressure fall greater than 20%). However one patient suffered a severe post-dural puncture headache which required an epidural blood patch. Continuous intra-thecal spinal analgesia is a potential alternative to continuous epidural analgesia in the relief of labour pain. PMID- 8009278 TI - Burns mass disasters in Singapore--a three decade review with implications for future planning. AB - OBJECTIVE: The main objective of this paper is to review three decades (1962 1991) of data relating to burns mass disasters in Singapore. DESIGN: Records of the Burns Centre, Singapore General Hospital were reviewed retrospectively. Only patients admitted were analysed in three separate groups in relation to the cause of the burns mass casualties and place of occurrence. SETTING: Patient selection was based on O'ya's criteria of burns mass disaster and were grouped into separate decades: Group A (1962-71), Group B (1972-81) and Group C (1982-91). INTERVENTION: Data collected will provide useful information on high risk sources, patterns and trends of burns mass disasters in Singapore. MAIN OUTCOME MEASURE: The data will provide the facts and will have implications for future planning and organisation of burn treatment facilities. RESULTS: There were 17 burns mass casualties and 257 patients admitted. The largest single admission was 76 in 1978. Group A had four, Group B had two and Group C had eleven disasters. Explosions (66%) and fires (30%) were the main causes of burns. The predominant place of occurrence in Group A patients was outdoor injuries (78%), Group B was work environment (100%) and Group C was evenly spread out: work environment (55%), indoors (36%) and outdoor (9%). Shipyards and fires were the largest sources of burns mass disasters. Other potential sources identified include hazardous materials, petrochemical industries, aviation industries, mass rapid transit train system, high rise fires, shopping complexes and imported disasters. CONCLUSION: The recommendation is to plan and reorganise burn treatment facilities. This is to cope with existing pattern, frequency and projected patterns of burn mass disasters which have occurred in other highly urbanised and populated countries. PMID- 8009279 TI - Simple aspiration of pneumothorax. AB - The effectiveness of simple aspiration of pneumothorax with an intravenous cannula was evaluated in 34 patients who would otherwise have been treated by intercostal tube drainage with underwater seal. The procedure was successful in 25 patients (73.5%). The following features were associated with a successful outcome: (a) age below 50 years, (b) absence of underlying lung disease, (c) pneumothorax size not exceeding 50%, (d) volume of air aspirated less than 3000 ml, and (e) no previous pneumothorax. There were no complications encountered. Successfully treated patients benefitted from a shorter hospitalisation stay. The potential use of this procedure in treating selected patients in an outpatient setting should be explored. PMID- 8009280 TI - Survival in hepatitis-B cirrhosis compared to alcoholic cirrhosis in patients with Child's C liver disease: a prospective study of endoscopic sclerotherapy for bleeding oesophageal varices. AB - A prospective comparative study was carried out on thirty-seven consecutive patients presenting with bleeding oesophageal varices at University Hospital, Kuala Lumpur. All patients received injection sclerotherapy if active bleeding was seen at the time of initial endoscopy, followed by repetitive courses of sclerotherapy to obliterate the varices. Predominant aetiological factors were hepatitis-B cirrhosis (43%) and alcoholic cirrhosis (30%). Chinese ethnic group accounted for 62.5% of hepatitis-B cirrhotics and Indian 73% of alcoholic cirrhotics. After excluding patients lost to follow-up, analysis of the remaining thirty-four patients showed reduced long-term survival in patients with Child's C disease. Log-rank analysis of survival curves between hepatitis-B cirrhosis and alcoholic cirrhosis in patients with Child's C liver disease showed no significant difference in long-term survival (p = 0.07). However, six deaths were seen in hepatitis-B cirrhosis compared to one death in alcoholic cirrhosis in the first eight months of follow-up. Most patients died from progressive liver failure. Median survival for Child's C hepatitis-B cirrhosis was 7.5 months whereas this had not been reached for Child's C alcoholic cirrhosis (median follow-up 11.6 months). We conclude that variceal haemorrhage in Child's C hepatitis-B cirrhosis is a bad prognostic sign and is associated with reduced survival with a median survival of 7.5 months despite control of the variceal bleed. PMID- 8009281 TI - Grade III open ankle fractures--a review of the outcome of treatment. AB - A retrospective review of fifteen patients with Grade III open ankle fractures, admitted to the Singapore General Hospital from January 1980 to December 1990 was done. Nine of the patients were males with a mean age of 47 years. Road traffic and industrial accidents accounted for 12 of the cases. Eleven of the fractures were associated with ankle dislocation or subluxation. Eleven of the fractures were fixed with plate and screws. Two of the ankles were stabilised with Steinmann pins inserted from the calcaneum to the lower end of the tibia. In ten cases the wounds were closed primarily or by delayed primary closure. One case required a flap to cover the defect and the rest were skin grafted. Eleven were immobilised in a plaster cast ranging from six to twelve weeks. Superficial infection was found in three cases and deep infection involving the bone and joint was present in three. Range of motion at one year was satisfactory in eleven but poor in two. Seven patients developed osteoarthritis of the ankle and three had ankle arthrodesis for pain and instability. PMID- 8009282 TI - Homozygous beta-thalassaemia: a review of patients who had splenectomy at the Royal Alexandra Hospital for Children, Sydney. AB - Twenty-four patients with homozygous beta-thalassaemia who had been splenectomised and currently on treatment were studied retrospectively. They were divided into two groups. Group A: who had splenectomy prior to commencement of any regular blood transfusion. The mean haemoglobin for this group rose from 5.5 gm/dl pre-splenectomy to 7.7 gm/dl post splenectomy (p < 0.001). Group B: who were on regular blood transfusion when they had their splenectomy and the mean blood transfusion requirement dropped from 317 ml/kg/yr to 230 ml/kg/yr of packed red cells following splenectomy (p < 0.001). Three patients who were on regular blood transfusion and desferrioxamine developed Yersinia enterocolitica infection. They presented with fever and signs of an acute abdomen. At laparotomy, 2 of the patients had acute appendicitis. All 3 appendices grew Yersinia enterocolitica and one patient also had a Yersinia enterocolitica septicaemia. If a patient develops fever and enteritis, desferrioxamine should be stopped temporarily and cotrimoxazole started as prophylaxis against systemic Yersiniosis. No cases of pneumoccocal sepsis was reported. PMID- 8009283 TI - Serum ferritin concentrations in transfusion dependent beta-thalassaemia. AB - Patients on a moderate red cell transfusion programme have iron overload where the concentrations of the serum ferritin were inappropriate to increases in the transfusion load as a result of limitations of apoferritin synthesis and conversion of ferritin into haemosiderin. This study confirms the limitations for the use of estimations of the serum ferritin to evaluate the iron status in patients with expected high overload as would be seen in patients on many years of maintenance red cell transfusions in the absence of iron chelation therapy. Poor compliance, inadequate dosage of Desferal (deferoxamine), and the late initiation of iron chelation therapy were factors that were considered in the patients with failure of response to iron chelation. PMID- 8009284 TI - Salpingitis isthmica nodosa: review of four cases from the General Hospital, Kota Bharu. AB - Four cases of salpingitis isthmica nodosa diagnosed from a total of 82 hysterosalpingograms, over a period of three years at the General Hospital, Kota Bharu, were reviewed. The diagnosis was made based on the radiographic appearance of globules of contrast medium in the periluminal tissues which were in continuity with the lumen of the fallopian tubes. Three of these patients had ectopic pregnancy. Diagnosis of salpingitis isthmica nodosa which is readily demonstrated by hysterosalpingogram, is extremely important because of its impact on ectopic pregnancy rates. Hysterosalpingography is indicated following ectopic pregnancy to show whether there is diverticulosis of the contralateral tube. By such knowledge, optimal treatment can be offered to patients wishing to attempt further conception. As the disease is relatively localised it is amenable to resection with reimplantation of the distal portion of the tube. PMID- 8009285 TI - Birth defects--the state of awareness. AB - As doctors and nurses are the primary sources of medical information, a simple survey was conducted in 1992 among doctors and nurses to determine their level of awareness of the incidence of and risk of having an abnormal as well as their knowledge of the use of ultrasound in pregnancy. Only 10% of doctors and 23% of nurses were aware that the general risk of having an abnormal baby is greater than 1%. Only 37% and 17% of doctors and nurses respectively were aware that the best time to screen for structural abnormalities was indeed at approximately 20 weeks gestation. PMID- 8009286 TI - Primary ovarian pregnancy: current diagnosis and management. AB - We reviewed five cases of ovarian pregnancy that were diagnosed at the Kandang Kerbau Hospital Histopathology Laboratory over three years. The clinical presentation, diagnosis and management of these patients are discussed in detail. This condition usually occurs in parous fertile women as evidenced by three of the five patients studied. It is probably an accidental event with no predisposing features as compared to the tubal pregnancy patient. The diagnosis has been aided by the recent advances in human chorionic gonadotrophin determination and ultrasound. Ultrasound, especially transvaginal ultrasound scanning has proven to be an invaluable tool in the diagnosis of this condition. Fertility after conservative surgical procedures does not appear to be affected and ovarian wedge resection or ovarian cystectomy is the treatment of choice. PMID- 8009287 TI - Meconium ileus--a rare cause of neonatal intestinal obstruction in Malaysia. AB - Meconium ileus, rare in Malaysia, accounts for 3.7% of all neonatal intestinal obstructions (excluding imperforate anus) seen in the University Hospital, Kuala Lumpur, from 1980-1990. This paper retrospectively reviews our clinical experience with 5 cases of meconium ileus seen over a 12-year period from 1980 1991 in the University Hospital, Kuala Lumpur. Three of the neonates were Malays, and two were Punjabis. Four of them were full-term and one preterm. The birth weights ranged from 1900 to 3700 g, with a mean of 2670 g. One of them also had a sibling with meconium ileus. Two of them were found to have foetal ascites and one had intestinal obstruction, antenatally by ultrasonography. The remaining two were symptomatic soon after birth. Extensive calcification was observed on plain abdominal radiographs in three babies and dilated bowels in the other two. All of them underwent laparotomy and uncomplicated meconium ileus was confirmed in two cases, meconium peritonitis in two and one meconium pseudocyst in addition to meconium peritonitis. There was one intraoperative death, and one long-term survivor who did not have cystic fibrosis. The remaining three did not have additional features suggestive of cystic fibrosis, and finally succumbed to respiratory infection. Sweat test was not done to confirm the diagnosis for logistic reasons. The management of such patients proved to be a challenge to clinicians because of the rarity of this condition. PMID- 8009288 TI - Two interesting cases of non-fatal melioidosis from Alexandra Hospital in Singapore. PMID- 8009289 TI - Unusual rectal perforation--an individualised approach to management. AB - The management of rectal perforations is controversial. Surgical repair or resection and anastomosis is usually undertaken with faecal diversion in the management of traumatic perforations. Primary repair without colostomy is less commonly employed. Five cases of rectal perforation seen in the Department of Colorectal Surgery, three from penetrating foreign objects and two from barium enema examination, are presented. The principles of management of patients with rectal perforations include faecal diversion, primary repair of rectal perforation and sphincter muscles, presacral drainage, parenteral antibiotics and distal bowel irrigation. This approach was used in the management of these five cases and the results were very satisfying. PMID- 8009290 TI - Early years of the out-patient services, Singapore (1880-1946). AB - This article traces the history of the Out-patient Services from its humble beginnings in the late 19th Century to just after World War II. The class of patients catered for, the disease pattern, the work done and benefits accrued are recorded. PMID- 8009291 TI - The community psychiatric nurse in Singapore. AB - The Community Psychiatric Nursing Service in Singapore began on 1st November 1988 in recognition of the need for continuous supervision of a group of psychiatric patients following discharge from hospital. The Community Psychiatric Nurse is able to provide mental health nursing care in a community setting. Her multiple roles are described. The various problems encountered and how she tackles them are discussed. The challenges posed and the future prospects are briefly addressed. PMID- 8009293 TI - [Digestive tract infections]. PMID- 8009292 TI - Psychiatry in dementia. AB - Dementia is a significant cause of psychiatric morbidity in the elderly. The burden of care on families is tremendous and there is an urgent need to develop dementia-related services in Singapore. The role of the psychiatrist in assessment is to diagnose dementia accurately, to exclude treatable causes, and to organise an individualised plan of management, which includes referring the patient to the appropriate agencies in order to minimise the disability and help the family cope. Support and education of the caregivers is of paramount importance and attending support groups provides the opportunity for caregivers to share their experiences and learn from one another. PMID- 8009294 TI - [Bone and joint infections]. PMID- 8009295 TI - [Nursing procedures. Meningitis]. PMID- 8009297 TI - [Pharmacology and the aged]. PMID- 8009296 TI - [Precautions to be taken when dealing with a contagious patient. Patient isolation]. PMID- 8009298 TI - [Care of patients at the end of their lives. A reality of nursing at home]. PMID- 8009299 TI - [Meningitis]. PMID- 8009300 TI - [Nutrition for the elderly]. PMID- 8009301 TI - [Sylvaine Monin. Interview by Fransoise Henin]. PMID- 8009302 TI - [Bladder catheterization]. PMID- 8009303 TI - [Acute lung diseases]. PMID- 8009304 TI - [Recruitment for home care services]. PMID- 8009305 TI - [The coordinating nurse]. PMID- 8009306 TI - [To support and strengthen relationships. The role of the coordinating physician]. PMID- 8009307 TI - [The social workers]. PMID- 8009308 TI - [The work of the nurse's aide. Care of an AIDS patient]. PMID- 8009309 TI - [The pediatric nurses]. PMID- 8009311 TI - [Home care services. Landmarks and perspectives]. PMID- 8009312 TI - [The physical therapists]. PMID- 8009310 TI - [Midwives]. PMID- 8009313 TI - [The pharmacist]. PMID- 8009314 TI - [The P3 orthesis. Individual protection for the nurse]. PMID- 8009315 TI - [Discussion groups ... but how? Considerations preliminary to their institution]. PMID- 8009316 TI - [Transfusion. Principles and controls]. PMID- 8009317 TI - [Home care services. Financing the facilities]. PMID- 8009318 TI - A review of completed suicides in the Lothian and Borders Region of Scotland (1987-1991). AB - A review of 400 completed suicides encountered during a 5-year period (January 1987-December 1991) in the Lothian and Borders Region of Scotland (LBRS) was conducted. The incidence was 9.4 per 100,000 with a M:F ratio of 2.4:1; the elderly had a significantly higher (P < 0.001) rate (9.9 per 100,000) compared to adolescents (3.3 per 100,000). Significantly (P < 0.001) more cases occurred in the rural communities. Overall, the peak incidence was in the 45- to 54-year age group. Drug overdose was the most common (39%) method used by both sexes and in both urban and rural communities; it was the first choice for virtually all age groups, and females exhibited greater preference. Analgesics and tricyclic antidepressants were the most common drugs used. Hanging (19.8%) was popular among the young and the elderly (> 64 years) suicides. Inhalation of car exhaust (13.3%) was a rural phenomenon and was common in the 25- to 54-year age group. Jumping from heights (9.8%) was more common in the urban areas; an increasing trend in the use of this method by females was possibly emerging. Drowning (8.3%) exhibited no particular pattern and the use of firearms was relatively uncommon (2.8%). This study and any subsequent assessment of socio-medical factors associated with completed suicide in this region should provide a basis for the formulation of preventive strategies. A continuous monitoring of the trends in the LBRS is necessary. PMID- 8009319 TI - Beginning schizophrenia observed by significant others. AB - As a part of the ABC Schizophrenia Study, a large-scale investigation of the influences of age and gender on the onset and course of schizophrenia, this study compared retrospective reports about emerging symptomatology during the early course of schizophrenia given by patients and their significant others in a representative first admission sample. The Interview for the Retrospective Assessment of the Onset of Schizophrenia (IRAOS), a comprehensive interview assessing early signs and symptoms, revealed that, in most cases, patients as well as informants perceived negative, depressive, and unspecific symptoms as early signs of the disorder. Pairwise agreement about the presence of certain symptoms was good for a limited number of signs, e.g., substance abuse, suicidal behavior, parental and marital role deficits, and paranoid delusions. These items mainly concern abnormal behaviors that can be observed easily. In contrast, there was little agreement between reports about perceptual and formal thought disorder, i.e., subjective internal phenomena. The results supported a continuity model for the observability of symptoms in schizophrenia. PMID- 8009320 TI - Expressed emotion in the families of patients with schizophrenia and its influence on the course of illness. AB - This paper presents the results of a study carried on an urban population in Belgrade investigating the connections between relapse in schizophrenia and the expressed emotion (EE) status of families where at least one of the patient's parents was a member of the household. The overall rate of high EE was just under 50%, in the middle of the range of values reported in studies carried out elsewhere. Relapse was found to be 10 times more frequent in patients whose families were rated high in EE. The sample consisted of 30 patients with hebephrenic schizophrenia and 30 with paranoid schizophrenia. The results suggested that these subtypes may be associated with different attributes of EE. Criticism was more frequent in families of patients with paranoid schizophrenia, while emotional overinvolvement was more frequent in families having a hebephrenic offspring. The different components of EE, suitably combined, may differentiate between the two subtypes of schizophrenia in terms of relapse rate. The relative odds for high criticism were similar for both subtypes, but for maternal overinvolvement (EOI) the odds were 10.5 for hebephrenic as against 2.3 for paranoid schizophrenia. Thus, EOI was more common in the families of those with hebephrenia and also led more frequently to relapse. There was also an inverse relationship between relapse rate and warmth, whether paternal or maternal. This was significant in both subtypes, and indicated that the threshold for the positive effect of warmth was higher for fathers than for mothers. Marital conflict was significantly related to relapse, mainly because it was associated with high EE.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8009321 TI - Burden on key relatives of patients with schizophrenia vs neurotic disorders: a pilot study. AB - The burden perceived by the key relatives of 27 schizophrenics and 19 patients with neurotic disorders, both with at least a minimal degree of personal/social disability and a current exacerbation of symptoms, was assessed by a self administered questionnaire. Only modest quantitative and qualitative differences between the two samples of key relatives were found. The burden perceived by the relatives of schizophrenics was more closely related to the patients' personal/social disability than that reported by the relatives of neurotic patients. The psychopathological features of schizophrenic patients that were perceived as the most burdensome were "negative" symptoms, whereas the burden reported by the relatives of neurotic patients was predominantly related to obsessive/compulsive and anxiety symptoms. PMID- 8009322 TI - First admission rates for schizophrenia in immigrants to The Netherlands. The Dutch National Register. AB - Data from the Dutch national register were examined in order to determine first admission rates for schizophrenia in the four largest immigrant groups to the Netherlands (from the countries of Surinam, the Netherlands Antilles, Turkey and Morocco). Rates for immigrants from Surinam and the Netherlands Antilles exceeded by far those of the native-born population. Differences in proportions of compulsory first admissions between young male immigrants from these countries and their native-born counterparts were small and statistically not significant. Rates of first admissions for young male immigrants from Morocco were also much higher than those for the native-born population, but rates for female immigrants from Morocco and for immigrants from Turkey were not increased. These results support British studies reporting an increased incidence of schizophrenia in Caribbean immigrants to the United Kingdom. PMID- 8009323 TI - Parental bonding instrument. Exploring for links between scores and obsessionality. AB - The view that those with obsessive compulsive disorder or obsessional personality have been exposed to overcontrolling and overcritical parenting is examined. Two measures of obsessionality (the Maudsley Obsessional-Compulsive Inventory and the Leyton Obsessionality Inventory) were completed by 344 nonclinical subjects. They also scored their parents on the Parental Bonding Instrument (PBI), a measure assessing perceived levels of parental care and overprotection, before and after controlling for levels of state depression, trait anxiety and neuroticism in the analyses. Those scoring as more obsessional returned higher PBI protection scale scores. Links with PBI care scale scores were less clear, essentially restricted to the Maudsley Inventory, and variably influenced by controlling other variables. PMID- 8009324 TI - Screening for psychiatric illness in primary care. A cross-sectional study in a Swedish health district. AB - A sample of 388 primary care patients in a Swedish health district were screened for psychiatric illness using the Hopkins Symptom Check List HSCL-25. General practitioner (GP) ratings of psychiatric illness and patient ratings of psychosocial problems were also included. Data concerning the patients' utilization of care and health insurance were recorded. According to the HSCL-25, 30.2% of the patients were probable psychiatric cases and 19.2% were psychiatric cases in need of treatment. According to GPs' independent ratings, 12.3% of the patients suffered from psychiatric illness requiring treatment. Psychiatric cases according to HSCL-25 were more often women, divorced, unemployed and living alone. During the year preceding index contact, psychiatric cases showed a higher utilization of primary care, as well as other somatic care. They also had more sick leave. Psychiatric cases perceived higher levels of psychosocial problems in areas of unemployment, work situation, private economy, child care and social isolation. The results of the study point to the interaction of psychological impairment, environmental stress and lack of social support in producing psychiatric illness. PMID- 8009325 TI - The psychometric properties of the Eating Attitude Test in a non-Western population. AB - The psychometric features of the Eating Attitude Test Questionnaire (EAT) are described in an Egyptian population of secondary school girls (n = 351). Confirmatory factor analysis, modelled on studies by Garner et al. (1982) and Eisler and Szmukler (1985), was conducted and pointed to the overall coherence of the EAT in this population. The assessment of the internal validity of each factor, however, showed a high level of consistency amongst the items representing the dieting factor, and a much lower level for those representing the bulimia factor. The results could justify the continued use of the EAT as a valid screening instrument for some aspects of eating morbidity, i.e. dieting and concern about weight and shape in non-Western populations. The analysis clearly suggested that another scale is required for bulimic behaviours. PMID- 8009326 TI - Reliability and validity of the Cambodian version of the 28-item General Health Questionnaire. AB - This study confirmed the reliability and validity of a Cambodian version of the 28-item General Health Questionnaire (GHQ-28). The GHQ-28 was tested on 223 adult Cambodians living in Dunedin, New Zealand, who were examined independently by a psychiatrist (P.C.) using the short Present State Examination (PSE). There were satisfactory internal consistencies for the whole scale and the subscales except the C scale. It correctly identified 84.4% of cases with a 3/4 cut-off (sensitivity 87.5%, specificity 82.8%), suggesting a discriminative power as good as its English version when used among Caucasian women in Dunedin. The four subscales were by no means independent, and concurrent validity tests with the PSE suggested that they provided additional information regarding somatic symptoms and anxiety, but not about social dysfunction and depression. PMID- 8009327 TI - The functional restoration approach to the treatment of chronic pain in patients with soft tissue and back injuries. AB - A prospective randomized study of 542 injured workers with continuing pain compared 271 workers who were treated at either one of two clinics that provided functional restoration with a control group of 271 subjects. Chronic pain was caused by low back injury in 78% of patients; 79% of those treated were at work 12 months after completion of treatment compared with 78% of the control subjects. When the patients were divided into subsets, based on the accident date and followed monthly, the duration of absence from work, the compensation costs, the disability award costs, and the total costs were less for those treated than the control subjects, but these were not statistically significant. Using the difference in total costs as a measure of relative success, back injuries had better results than other injuries in this study. PMID- 8009328 TI - Does nonsurgical pain center treatment of chronic pain return patients to work? A review and meta-analysis of the literature. AB - Evidence in the literature relating to return to work as an outcome variable for nonsurgical treatment for chronic pain was examined. Study selection criteria were as follows: a detailed definition of patient work status, delineation of work status pre-treatment and at follow-up, and documentation of the proportion of patients employed at follow-up. Of 171 studies reviewed, 37 fulfilled these selection criteria. Because the data were objective in nature, they were abstracted by the senior author only. For the coded variables of time to follow up, proportion of patients working pre-treatment and at follow-up and number of patients, descriptive statistics and correlations were calculated. Change in employment status at follow-up was significant (P < .005) for all groups examined. In addition, comparisons for work outcome between treated patients versus patients rejected due to lack of insurance, and between treated patients versus patients who dropped out of treatment were both significant (P < .001). The mean difference in employment at follow-up for treated patients versus those not treated was approximately 50%. The proportion of patients working increased from 20% to 54% post chronic pain nonsurgical treatment. Correlation analyses did not find a significant trend in percent employed with time to follow-up. These results indicate that (1) chronic pain nonsurgical treatment does return patients to work; (2) increased rates of return to work are due to treatment, and (3) benefits of treatment are not temporary. PMID- 8009329 TI - Sub-axial cervical dissociation. Anatomic and biomechanical principles of stabilization. AB - Four fresh human cadaver spines were analyzed during and after disruptive hyperflexion and hyperextension to characterize the pathoanatomy of three-column cervical dissociation. In both flexion and extension, the posterior longitudinal ligament and facet capsules provided the greatest resistance to disruption. At low loading rates, all structures failed through the soft tissues. Three-column disruption caused by either pure flexion or extension resulted in marked elongation of the neural axis, inconsistent with cord survival. Biomechanical studies were carried out in seven additional fresh frozen human cadaver specimens to determine the most rigid method of internally stabilizing three-column cervical dissociations. Specimens were tested in compressive flexion and distractive extension to evaluate stability of anterior, posterior, and combined fixation constructs. Specimens were tested intact, after partial two-column disruption, and after complete three-column dissociation. Posterior wiring provided significantly better flexural stability in two- rather than three-column disruptions. Posterior wiring reduced posterior displacement in two-column partial disruptions to 25% of control. In three-column dissociations, posterior wiring only reduced posterior displacement to 50% of control. In extension, posterior wiring was ineffective in preventing displacement. Anterior plating, used alone, tolerated only 37% of the maximum flexion moment before early failure. On the other hand, combined anterior plating and posterior Roger's wiring reduced posterior displacement in flexion to 20% of control, while reducing anterior displacement in extension to 50% of control. This improvement over the other constructs was statistically significant. In highly unstable cervical injuries, Morscher anterior cervical plates and modified Roger's posterior wire fixation provide a safe, rigid construct that protects neural function while allowing early and aggressive mobilization.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8009330 TI - Robinson anterior cervical fusion comparison of the standard and modified techniques. AB - In 1990 the authors modified the Robinson anterior cervical interbody fusion technique by burring the endplates to expose subchondral bone. The authors compared 31 patients having the standard technique and 29 patients having the modified technique to evaluate 1) setting of the bone graft, 2) kyphotic angulation, 3) pseudarthrosis rate, and 4) pain outcome. In the standard Robinson fusion technique, the average loss of height across the fused segments was 0.8 mm and the average increase in kyphosis 4.9 degrees. Values for the modified technique were 1.9 mm and 3.1 degrees, respectively. The change in height was statistically significant (P = .01), as was the difference in angulation (P = .028), though the latter was in the opposite direction predicted. The pseudarthrosis rate using the modified technique decreased to 4.4% per level. Pain outcome for the two groups was equivalent. Burring of the endplates for anterior cervical interbody arthrodesis results in a detectable but not clinically important amount of graft settling with a higher success rate for arthrodesis. PMID- 8009331 TI - The surgical management of ossification of the posterior longitudinal ligament in 43 north americans. AB - From 1989 to 1992, 43 of 174 (25%) consecutive North Americans had cervical ossification of the posterior longitudinal ligament (OPLL). After the non-random selection of anterior corpectomies and fusions, anterior discectomies and fusions, or five-level laminectomies, the preoperative and postoperative outcomes of the OPLL patients were compared using Ranawat's neurological classes and grades. Patients who had anterior OPLL surgery exhibited superior outcomes compared with those who had laminectomies. Specifically, the 20 patients who underwent corpectomies and had the most severe preoperative deficits, had the best postoperative results; the 13 discectomy patients, with the least severe preoperative deficits, had intermediate recoveries, whereas the ten laminectomy patients, with intermediate preoperative neurologic dysfunction, had biased future surgical choices to favor more anterior approaches. PMID- 8009332 TI - Ossification of the posterior longitudinal ligament in evolution in 12 patients. AB - Ossification of the posterior longitudinal ligament (OPLL) in evolution (OEV), an early form of OPLL, was newly discovered in 12 of 43 (28%) patients who had OPLL and underwent operations from 1989-1992. Magnetic resonance imaging and CT studies of OEV patients who were younger, in their mid-forties, and had less severe spastic myeloradiculopathy, showed hypertrophied posterior longitudinal ligaments containing punctate ossification at disc spaces and contiguous endplates, with occasional extension behind vertebral bodies. However, both location and neuroradiologic appearance allowed OEV to be confused readily with disc or spondylotic disease. Only heightened awareness of the clinical and radiographic findings of OEV allowed the correct diagnosis. The appropriately extended anterior discectomies or corpectomies with fusions contributed to better outcomes. PMID- 8009333 TI - The influence of age and gender on lumbar spine sagittal plane range of motion. A study of 1126 healthy subjects. AB - Inclinometers have been recommended for the measurement of lumbar spine range of motion (ROM) in the assessment of disability. Range of motion thresholds that determine impairment ratings have been established without regard to age and gender or variances of the measures. This investigation determined the effect of gender and age on lumbar spine sagittal plane ROM in 1126 healthy male and female volunteers. Results indicate that distinct differences exist between men and women in flexion angle and extension angle, whereas little difference exists between genders for total lumbar sagittal ROM. Total sagittal ROM, flexion angle, and extension angle declined as age increased. Because of the high degree of variability in the measurements, detecting impairment in ROM with this method is problematic. PMID- 8009334 TI - Electromyographic activity of selected trunk and hip muscles during a squat lift. Effect of varying the lumbar posture. AB - Electromyographic (EMG) activity of selected hip and trunk muscles was recorded during a squat lift, and the effects of two different lumbar spine postures were examined. Seven muscles were analyzed: rectus abdominis (RA), abdominal obliques (AO), erector spinae (ES), latissimus dorsi (LD), gluteus maximus (GM), biceps femoris (BF), and semitendinosus (ST). The muscles were chosen for their attachments to the thoracolumbar fascia and their potential to act on the trunk, pelvis, and hips. Seventeen healthy male subjects participated in the study. Each subject did three squat lifts with a 157-N crate, with the spine in both a lordotic and kyphotic posture. The lift was divided into four equal periods. EMG activity of each muscle was quantified for each period and normalized to the peak amplitude of a maximal voluntary isometric contraction (MVIC). A two-way analysis of variance (ANOVA) for repeated measures was used to analyze the effects of posture on the amplitude and timing of EMG activity during the lift. Two patterns of EMG activity were seen: a trunk muscle pattern (RA, AO, ES, and LD) and a hip extensor pattern (GM, BF, ST). In the trunk muscle pattern (TP), EMG activity was greatest in the first quarter and decreased as the lift progressed. In the hip extensor pattern (HP), EMG activity was least in the first quarter, increased in the second and third quarters, and decreased in the final phase of the lift. Differences (P < .05) were seen among subjects and in the timing of the muscle activity in all muscles.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8009335 TI - Passive stiffness of the lumbar torso in flexion, extension, lateral bending, and axial rotation. Effect of belt wearing and breath holding. AB - This work investigated the passive bending properties of the intact human torso about its three principal axes of flexion: extension, lateral bending, and axial rotation. Additionally, the effects of wearing an abdominal belt and holding the breath (full inhalation) on trunk stiffness was investigated. The torsos of 22 males and 15 females were subjected to bending moments while "floating" in a frictionless jig with isolated torso bending measured with a magnetic device. Belts and breath holding appear to stiffen the torso about the lateral bending and axial rotation axes but not in flexion or extension. Torsos are stiffer in lateral bending and capable of storing greater elastic energy. Regression equations were formulated to define stiffness and energy stored for input to biomechanical models that examine low back function and for bioengineers designing hardware for stabilization and bracing or investigation of traumatic events such as automobile collision. PMID- 8009336 TI - The effect of electromagnetic pulsing on posterior lumbar spinal fusions in dogs. AB - This study evaluated the effect of pulsed electromagnetic fields (PEMF) on the healing of lumbar spinal fusions. Bilateral posterior facet fusions were performed at L1-2 and L4-5 in 24 adult mongrel dogs. After surgery, eight animals were stimulated with a pulse burst type signal (PEMF) for 30 minutes a day, and eight animals were stimulated with the same PEMF for 60 minutes a day. The remaining eight animals received no active PEMF stimulation and served as controls. Four animals from each group were euthanatized at 6 and 12 weeks, and the facet fusions were evaluated using high resolution radiographs and routine histology. No statistical difference in the radiographic or histologic appearance of the fusion mass could be detected between the stimulated and control groups at either 6 or 12 weeks. The results of this study suggest that PEMF stimulation had no effect on the healing of the primary posterior spinal fusions in this controlled experimental canine model. PMID- 8009337 TI - Pedicular transvertebral screw fixation of the lumbosacral spine in spondylolisthesis. A new technique for stabilization. AB - Controversy exists about which method is most appropriate for treating moderate- to high-grade spondylolisthesis and symptomatic pseudarthrosis. The authors report preliminary results of pedicular transvertebral screw fixation, a new technique for stabilizing the lumbosacral junction in moderate- to high-grade spondylolisthesis. Using this technique, fusion was successful in three patients, two with an established pseudarthrosis. Pedicular transvertebral screw fixation provides immediate three-column stabilization of the lumbosacral junction. The technique is safe, effective, and employs instrumentation common to spine surgery. Its use in high-grade slips makes the technique more simple to perform than other methods of lumbosacral stabilization. PMID- 8009338 TI - Management of retroperitoneal chylous leakage. AB - Lymphatic complications are uncommon after spinal surgery. Postsurgical collections of lymph may result in chyloma, chylothorax, chylous ascites, or chyloretroperitoneum. Recommended treatment of chylothorax or chylous ascites includes drainage, and a low-fat diet using medium-chain triglyceride or total parenteral nutrition. The only reported case of chyloretroperitoneum concluded with a recommendation for retroperitoneal drainage. The authors present a series of three patients who underwent anterior spinal procedures complicated by retroperitoneal lymphatic injury. All three were treated without retroperitoneal drains, and at follow-up, none has shown any adverse sequelae from this method of treatment. The authors disagree with past recommendations for drainage of the retroperitoneal space because this may prolong drainage and deplete nutrition. PMID- 8009339 TI - Reversible urinary retention secondary to excessive morphine delivered by an intrathecal morphine pump. AB - Reversible complication of intrathecal morphine delivered by an implanted pump is described in one patient. The patient was evaluated initially using a contrast CT of the thoracic spine as well as urodynamics studies. After decreasing the intrathecally administered morphine from 2 mg/24 hr to .5 mg/24 hr, the patient's neurogenic bladder reversed within 4 days. Implanted pumps to deliver intrathecal narcotic medications are being used currently to treat intractable pain. This is a case report of reversible urinary retention secondary to the intrathecal narcotic. PMID- 8009340 TI - Anatomic consideration in the anterior approach to the sacro-iliac joint. AB - Anatomical study of L4 nerve branch, L5 nerve root, and bony stock in the sacroiliac region was performed in cadaveric specimens to provide anatomical references for anterior fixation of the sacroiliac joint. At 1 cm intervals along the sacro-iliac joint, the distance to the lateral border of the L4 nerve branch (to the lumbosacral trunk) and the L5 nerve root was measured. Computed tomography scans and cadaveric sectioning of the sacro-iliac region were performed to evaluate the bony stock available for fixation and the optimal screw direction to prevent neurologic damage. At 4 cm above the pelvic brim, the L4 nerve branch was a mean distance of 23 mm medial to the sacro-iliac joint, whereas the L5 nerve root was 26 mm. At the pelvic brim, those distances decreased to 10 mm for both structures. Four centimeters cephalad to the pelvic brim, the AP dimension of Sl complex was decreased. Screws that were 1 cm medial to the Sl joint and directed posteriorly and parallel to the joint did not endanger neurologic structures. At four centimeters above the pelvic brim, there is less danger of neurologic injury; however, a decrease in sacral bony stock may affect fixation. PMID- 8009341 TI - Complete anterior fracture-dislocation of the fourth lumbar vertebra. PMID- 8009342 TI - Intrathecal administration of oxytocin induces analgesia in low back pain involving the endogenous opiate peptide system. AB - STUDY DESIGN: The effect of oxytocin on low back pain in patients and its mechanism in rats were investigated. METHODS: Intrathecal injection, radioimmunoassay, and potassium iontophoresis tail-flick test were used to investigate the effect of oxytocin. RESULTS: In humans, acute and chronic low back pain causes a marked change of oxytocin content within cerebral spinal fluid and plasma; oxytocin relieves low back pain (ED50 0.172 in chronic and 0.121 micrograms/kg in acute). In rats, oxytocin had a dose-related analgesic effect (ED50 0.067 micrograms/kg). At high levels, oxytocin induced locomotor ataxia (ED50 17.915 micrograms/kg) and death (LD50 27.224 micrograms/kg). Oxytocin antagonist [d(CH2)5, Tyr(Me)2, Orn8]-vasotocin and opiate receptor-blocker naloxone could reverse oxytocin-induced analgesia. Oxytocin also increased beta endorphin, L-encephalin, and dynorphin A1-13 contents in the spinal cord, whereas oxytocin antagonist caused a decrease. CONCLUSIONS: These results suggest that oxytocin induces analgesia in low back pain involving the endogenous opiate peptide system and may be effective and safe in acute and chronic low back pain. PMID- 8009344 TI - Chronic low back pain: The relationship between patient satisfaction and pain, impairment, and disability outcomes. AB - STUDY DESIGN: Treatment outcomes for low back pain have been measured by varying standards of pain, impairment, and disability. This study examines the relationship between these three outcomes and treatment satisfaction in patients with chronic low back pain (CLBP). METHODS: Ninety CLBP patients underwent initial pain (VAS), impairment (PIS), and disability (OPQ) evaluations. RESULTS: Correlation coefficients between initial VAS, PIS, and OPQ were all less than 0.50. At 5-year follow-up, pain and disability scores were closely matched, more with lower mean scores among workers (P = 0.04 and 0.001). For 65 rehabilitation participants, 5-year patients satisfaction scores did not relate closely with VAS, PIS, and OPQ improvements during treatment (r = 0.15, 0.01, and 0.14). Five year satisfaction correlated weekly with current pain and disability (r = 0.32, 0.36). Satisfaction levels were higher for workers after 1 year (P = 0.01), and after 5 years (P = 0.34. CONCLUSIONS: This study suggests that CLBP patients and their health care practitioners mutually set distinct pretreatment pain, impairment, and disability goals and judge outcomes accordingly. PMID- 8009345 TI - Validity of patient reporting and predictive value of industrial physical work demands. AB - STUDY DESIGN: This prospective study analyzed industrial physical work demands. The patients (n = 103), sick-listed 8 weeks because of low back pain, were industrial blue-collar workers in the car manufacturing industry. OBJECTIVES: This study described industrial physical work demands in a sample of patients with subacute low back pain (LBP), studied the agreement between reported and observed work postures, estimated compression load on the spine, and determined the predictive validity of industrial physical work demands and occupational LBP handicap. METHODS: The patients (n = 103), sick-listed 8 weeks because of low back pain, were industrial blue-collar workers in the car manufacturing industry. Industrial physical work demands were reported by the patients and also studied at the work place. The patients' work demands commonly included lifting, forward bending, standing and twisting, working with the hands above the shoulders, and a compression load on the spine of more than 2000 N, and more than 60% of the patients believed that work demands caused their LBP. RESULTS: Substantial or moderate agreement was found more often between the patients' reports and the physical therapists' observations of work postures. None of the studied industrial physical work demands predicted the rate of return to work or the sick leave during the second follow-up year. CONCLUSION: The correlations between reported or observed physical work demands, individual physical capacity, individual psychological capacity, spare-time activities, other factors and LBP are not clear. A workplace visit made by a physical therapist may facilitate the rehabilitation process, especially since many patients believed that work factors caused their LBP. PMID- 8009343 TI - Measuring residual functional capacity in chronic low back pain patients based on the Dictionary of Occupational Titles. AB - STUDY DESIGN: This study designed and tested a functional battery based on the Dictionary of Occupational Titles (DOT). OBJECTIVES: Such a battery can be used to measure residual functional capacity (RFC) in chronic pain patients (CPP) and results can be matched against the demand minimum functional capacities (DMFC) of DOT jobs. SUMMARY OF BACKGROUND DATA: Physicians have difficulty translating medical impairment into functional limitation and thereby establishing the RFC of CPPs. METHODS: The DOT, a USA government publication, provides information about physical demands of every USA job according to 36 factors and subfactors. The authors defined and developed a functional battery based on these factors/subfactors. This battery was tested on 67 consecutive CPPs to determine the percentage of CPPs able to pass specific job factors and the full battery and return to some DOT job, and evaluated the effects of pain on battery performance. The data were factor analyzed. RESULTS: The battery determined if CPPs could perform DOT job factors and had the necessary RFC to be placed in a DOT job. The vast majority of CPPs could not pass the full battery and the presence of pain and original job classification predicted whether a CPP could perform a job factor. Factor analyses grouped the factors into four independent categories supporting the design of the battery. CONCLUSION: The battery can assess whether CPPs are able to return to work. PMID- 8009346 TI - Reduction of back and posterior pelvic pain in pregnancy. AB - STUDY DESIGN: This study analyzed an education and training program concerning back and pelvic problems among pregnant women. OBJECTIVE: The program was aimed at reducing back and pelvic posterior pain during pregnancy. SUMMARY OF BACKGROUND DATA: Low back and posterior pelvic pain accounts for the majority of sick leave among pregnant women. No previous study has suggested any type of solution to this problem. METHODS: Four hundred and seven consecutive pregnant women were included in the study and randomly assigned into three groups. Group A served as controls while different degrees of interventions were made in groups B and C. RESULTS: Serious back or posterior pelvic pain developed in 47% of all women. Pain-related problems were reduced in groups B and C (P < 0.05), and sick leave frequency was reduced in group C (P < 0.01). For some of the women in this group, pain intensity was also reduced 8 weeks post partum (P < 0.05). Weekly physical exercise before pregnancy reduced the risk for back pain problems in pregnancy (P < 0.05). A non-elastic sacro-iliac belt offered some pain relief to 82% of the women with posterior pelvic pain. CONCLUSIONS: An individually designed program reduced sick leave during pregnancy. Working with groups was less effective. Differentiation between low back and posterior pelvic pain was essential. Good physical fitness reduced the risk of back pain in a subsequent pregnancy. Reduction of posterior pelvic pain by a non-elastic pelvic support was experienced by 82% of the women with posterior pelvic pain. PMID- 8009347 TI - Spinal stenosis and health status. AB - STUDY DESIGN: This study examined the hypothesis that a small adult vertebral canal is a marker of early impairment of growth, and that other sensitive systems may be impaired similarly, producing an adult relationship among a small canal, poor health, and academic ability. OBJECTIVES: Comparisons of health and some aspects of academic ability were made between patients whose canals were above and those below the mean at L5. METHODS: Seventy-five patients were examined, 42 men and 33 women. They had comprehensive cardiovascular, respiratory, and digestive system health assessments. Their post-school qualifications were recorded, and they were assessed by the Mill Hill vocabulary test and the progressive matrices test. RESULTS: Twenty-two men and 21 women had canals above the mean, and 20 men and 12 women had canals below the mean. A significant difference did not exist in the age of those with wider and narrower canals. Cardiovascular symptoms and gastrointestinal symptoms were more common in men and women with narrower canals (P = 0.04 and 0.048), but there was no significant differences in respiratory symptoms. Those with wider canals had more post-school qualifications than those with smaller canals (P = 0.04), and in men, their performance in the Mill Hill vocabulary test and the progressive matrices test approached significance (P = 0.08 and 0.06). CONCLUSIONS: The association between a smaller vertebral canal and impairment of health and certain intellectual abilities may result from an adverse environment that affects several growing systems early in life. If the small canal is a marker of a generalized developmental disturbance, it is, to some degree, preventable. PMID- 8009349 TI - Ligamenta flava in lumbar disc herniation and spinal stenosis. Light and electron microscopic morphology. AB - METHODS: Ligamenta flava obtained from nine patients with lumbar disc herniation and ten patients with lumbar stenosis were studied at histologic, histochemical, and ultrastructural levels. Lumbar ligamenta flava removed from six patients who underwent surgeries for thoracolumbar fractures were used as controls. RESULTS: Ligamenta flava from control subjects consisted of large elastic fibers, thin bundles of collagen fibers, and few spindle-shaped fibroblasts. In proximity to the laminal insertion, the ligaments had fibrocartilagineous features. In the control subjects who were age 50 or older, the cells decreased in number and areas that had fewer and thinner elastic fibers and a more abundant collagen component were visible occasionally. In patients with disc herniation, the ligaments had similar morphologic features to those of the controls of similar ages. The ligamenta flava from patients with lumbar stenosis showed areas of fibrosis in which the cells were often represented by actively synthesizing fibroblasts and areas of chondroid metaplasia. Degenerating elastic fibers were seen occasionally, while calcified areas were observed often. CONCLUSIONS: Ligamenta flava undergo slight fibrotic and chondrometaplastic changes with aging. No peculiar changes occur in patients with disc herniation. In spinal stenosis, fibrotic changes, chondroid metaplasia, and calcification reduce the elasticity of the ligaments, which may thus bulge into the spinal canal in the standing position even if they are normal in thickness. PMID- 8009348 TI - Innervation of the spondylolysis "ligament". AB - SUMMARY OF BACKGROUND DATA: Spondylolysis of the lower lumbar vertebrae is a non united childhood fracture of the arch of the vertebra, persisting into adult life. Symptoms of disabling low back pain appear in a minority of patients, usually for the first time in adulthood. This pain is considered to arise from several separate sources, one of which may be the spondylolysis ligament. STUDY DESIGN: The innervation of the ligament has been investigated immunohistochemically. METHODS: Specimens from eight patients were divided longitudinally for histology including hematoxylin and eosin, toluidine blue, and elastic van Gieson. Histochemistry involved immunostaining for the neuropeptides: protein gene product, calcitonin gene related peptide, substance P, vasoactive intestinal peptide, and the c-flanking peptide of neuropeptide Y. RESULTS: Immunoreactivity to calcitonin gene-related peptide, the c-peptide of neuropeptide Y, and vasoactive intestinal peptide was identified in the ligament or in the adjacent adipose tissue. CONCLUSION: The movement that the ligament allows at the fracture site may result in stimulation of the nerve endings both in the ligament and in the surrounding soft tissue. PMID- 8009350 TI - Lumbar disc degeneration and atherosclerosis of the abdominal aorta. AB - STUDY DESIGN: This study analyzed the relationship of disc degeneration to atherosclerotic changes in the abdominal aorta and stenosis of the ostia of the lumbar and middle sacral arteries, 86 plain radiographs of lumbosacral spines, and the corresponding abdominal aortas were evaluated in connection with routine autopsy. RESULTS: Disc degeneration, advanced atherosclerotic manifestations, and stenosis of the ostia of the lumbar and middle sacral arteries all increased with age (P < 0.001). After partial rank correlation analysis, keeping the effect of age constant, there was still a statistically significant association between the grade of disc degeneration and stenosis of the ostia of the arteries supplying the disc. The association was stronger at upper lumbar levels (0.001 < P < 0.01) than at lower ones (0.01 < P < 0.05). Furthermore, with complicated lesions in the abdominal aorta, disc degeneration at all lumbar levels increased. CONCLUSIONS: Atherosclerosis in the abdominal aorta and especially stenosis of the ostia of segmental arteries may play a part in lumbar disc degeneration. PMID- 8009351 TI - Idiopathic coccygodynia. Lateral roentgenograms in the sitting position and coccygeal discography. AB - STUDY DESIGN: The authors hypothesized that the source of coccygodynia was a lesion of the coccygeal disc. OBJECTIVES: This study analyzed the motion of the painful coccyx in the sitting position as compared with the lateral decubitus in a patient and a control group and reported the first results of coccygeal discography (dynamic study). SUMMARY OF BACKGROUND DATA: Coccygodynia are usually attributed to soft tissue injuries or psychologic disturbances. No previous study has assessed the coccygeal discs as a source of pain. METHODS: Fifty-one patients with coccygodynia and 51 controls sustained a dynamic study. Coccygeal mobility was documented by superimposing graph paper with a double reading. The accuracy of the measurement was +/- 2.6 degrees intra- and interobserver variations 15.3 and 12.5%. This dynamic study was followed by coccygeal discography in the patient group. RESULTS: An abnormal motion (luxation or hypermobility) of the coccyx that occurred in the sitting position and spontaneously was reducible when placed in the lateral decubitus position was found in 25 patients. Such lesions could be responsible for the pain because no similar findings were seen in the controls and coccygeal discography was positive in these cases. Of the 26 patients with a normal dynamic study, coccygeal discography, using a combination of provocation and anesthetization, was positive in 15 of 21. CONCLUSIONS: Common coccygeal pain could come from the coccygeal disc in approximately 70% of cases. PMID- 8009352 TI - In vivo diurnal variation in intervertebral disc volume and morphology. AB - STUDY DESIGN: Three-dimensional reconstructions of MRI scans measured volume, height, and diameter of intervertebral discs. These measurements were made in vivo. OBJECTIVES: This study documented diurnal change in lumbar disc volume and morphology. The authors studied the pattern of this change over the disc levels that were examined and documented individual differences. SUMMARY OF BACKGROUND DATA: There is a diurnal pattern of standing heights. The majority of this diurnal height change can be accounted for by height loss within the intervertebral disc, which bulges radially with loading. These studies have been performed in vivo. METHODS: Eight normal males were studied using two protocols. In one, the volunteers were in the supine position for 6 hours before MRI scanning. In the other, volunteers spent 4 hours standing and 3 hours sitting before MRI scanning. Three-dimensional MRI scanning was carried out on the L3-4, L4-5, and L5-S1 discs. RESULTS: Volume height and AP diameter of the lumbar intervertebral discs decreased significantly after the protocol of a day's activity. The mean decrease in disc volume at the L3-4 level after standing was 21.1%. At the L4-5 level, it decreased a mean of 18.7%, whereas at the L5-S1 level, there was a 21.6% mean decrease. CONCLUSIONS: The mean simulated diurnal volume decrease in the lower three lumbar discs is 16.2%. Most of the diurnal loss in disc height is due to volume loss. The effect of radial bulging is minimal. PMID- 8009353 TI - Anthropometric variables, self-efficacy beliefs, and pain and disability ratings on the isokinetic performance of low back pain patients. AB - OBJECTIVES: This study investigated how age, sex, height, body weight, self efficacy beliefs, pain, and subjective disability predict the performance of low back pain patients on an isokinetic trunk muscle test. METHODS: One hundred and five patients participated in the study. Dependent variables were isokinetic flexion and extension strength measured as total work done at speeds 50, 100, and 150 degrees/second. RESULTS: The anthropometric measures were poor predictors, height being the only significant one. Body weight and age were of no relevance for the performance. Subjective pain and disability had negative effects on the performance of men, but not of women. Self-efficacy beliefs, i.e., the patient's belief in his or her capability to endure physical activities, was the most powerful predictor. CONCLUSION: For the purpose of validation, standardization, and interpretation of isokinetic performance in low back pain patients, these factors should be taken into account. PMID- 8009354 TI - Anular incision technique on the strength and multidirectional flexibility of the healing intervertebral disc. AB - STUDY DESIGN: This study used a sheep model to biomechanically analyze the healing strength of the anulus fibrosus after two types of anular incisions. OBJECTIVE: This study evaluated whether the type of anular incision made at the time of lumbar discectomy plays a role in the subsequent healing strength of the anulus and the biomechanical flexibility of the corresponding motion segment. METHODS: Two types of anular incision, a full thickness removal of a box or window of anulus and a full thickness straight transverse slit through the anulus, were made in the intervertebral discs of 18 adult sheep. After healing times of 2, 4, and 6 weeks, the intervertebral discs were tested versus control levels for strength of anular healing and biomechanical flexibility of the corresponding motion segment. RESULTS: The box incised discs showed a significantly greater loss in strength during the early healing phase (2 to 4 weeks) and a longer response before recovering anular strength when compared with the slit-incised discs. The type of incision also affected the multidirectional flexibility of the motion segments in a differentiated manner. Larger amounts of motion were seen with the box incision when compared with the slit incision at all time periods and in all pure moments. CONCLUSION: The technique of anular incision plays a definite role in the timing and strength of subsequent anular healing. The box incision through the anulus led to significantly weaker healing than did the slit incision in the early healing phase (2-4 weeks). Also, larger amounts of motion were seen in the vertebral motion segments of those discs undergoing box incision when compared with slit or control levels. PMID- 8009355 TI - Hydroxyapatite enhancement of posterior spinal instrumentation fixation. AB - STUDY DESIGN: The ability of hydroxyapatite (HA) materials to enhance the fixation strength of posterior spinal instrumentation was examined in 19 adult mongrel dogs. METHODS: Sixteen dogs underwent bilateral placement of lumbar transpedicular screws from L1 to L6, sacral alar screws, and posterior iliac rods. The six transpedicular screw test groups included standard and plasma sprayed HA-coated screws with the recommended insertion technique, standard and HA-coated screws with a poor initial fit insertion technique using an oversized pilot hole, and HA-grout augmentation of standard and HA-coated screws with a poor initial fit. The sacral alar screws and posterior iliac rods were either uncoated or HA-coated. Six dogs were killed immediately; ten dogs were killed at 6 weeks, and the fixation elements were mechanically tested or histologically examined. Three additional dogs and synthetic bone material were used for additional baseline mechanical testing. RESULTS: The strength of standard screws with recommended insertion did not change after 6 weeks in vivo. HA-coated screws were initially 13% less resistant to pull out than standard screws, but this difference was not significant at 6 weeks. Screws inserted with a poor initial fit technique were significantly weaker initially; at 6 weeks, pull-out strength was similar to the standard screws properly inserted. The HA-grout material significantly enhanced pull-out strength for both screw types at 6 weeks. Sacral alar screw pull-out strength was not significantly different between standard and HA-coated screws initially or at 6 weeks. HA-coated rods were initially twice as resistant to pull out than standard rods and became stronger after 6 weeks in vivo, whereas standard rods became significantly weaker. Histologically, the quantity and morphology of bone around all implants was similar, with HA-coated rods and screws demonstrating regions of direct attachment to bone. An osteoconductive response and new bone formation was observed within the HA-grout material. Scanning electron microscopic observation of mechanically tested implants revealed a shear failure of surrounding bone (and HA if present) at the screw outer thread margin or at the bone-metal or HA-metal interfaces for the posterior iliac rods. CONCLUSIONS: The strength of poorly inserted transpedicular screws was significantly enhanced in vivo by the resorbable HA-grout material. The lower strength of HA-coated screws was attributed to screw geometry changes resulting from the coating process, and modifications of screw coating are recommended. PMID- 8009356 TI - Multidirectional stability of the Graf system. AB - STUDY DESIGN: To assess the biomechanical influences of the Graf fixation system on the spine, motion segments were tested. In normal spines, destabilized and restabilized with the Graf system conditions, the range of motion and flexibilities were found under various loading conditions. OBJECTIVES: These results should explain how the Graf Fixation system affects the biomechanical response of a motion segment. METHODS: Motion segments (L2-3) and (L4-5) were subjected to these loading conditions: compressive loading, flexion-extension, lateral bending, and axial rotation moments. During the loading, the main and coupled motions were measured, and flexibilities were computed. The position of the balance point in axial loading was also determined. The motion segments were tested under three conditions: intact, destabilized, and restabilized. The destabilization consisted of a bilateral total laminectomy (pedicle-to-pedicle). Restabilization was affected with the Graf stabilization system, consisting of polyester bands between pedicle screw implants. RESULTS: The total laminectomy significantly changed the balance point location by moving it forward. The restabilized motion segment had a balance point more similar to normal conditions. The mean compressive compliance was significantly less after application of the Graf system compared with destabilization. The range of motion for flexion-extension and axial rotation was significantly reduced for the main motion with the Graf system. For lateral bending, the main and coupled rotations were affected significantly, with lateral bending and flexion-extension motion reduced and axial rotation increased after restabilization. Restabilization decreased the flexibility of the destabilized motion segment for all of the moments. CONCLUSIONS: The Graf fixation system reduced the range of motion and the flexibility values in some loading conditions. These results only assess the immediate stabilization characteristics of this implant system in cadaveric material. Further research should address the fatigue characteristics. PMID- 8009357 TI - Geometric changes in the cervical spinal canal during impact. AB - SUMMARY OF BACKGROUND DATA: Although the extent of injury after cervical spine fracture can be visualized by imaging, the deformations that occur in the spinal canal during injury are unknown. STUDY DESIGN: This study compared spinal canal occlusion and axial length changes occurring during a simulated compressive burst fracture with the residual deformations after the injury. METHODS: Canal occlusion was measured from changes in pressure in a flexible tube with fluid flowing through it, placed in the canal space after removal of the cord in cadaver specimens. To measure canal axial length, cables were fixed in C1 and led through the foramen transversarium from C2-T1, then out through the base, where they were connected to the core rods of linearly variable differential transformers (LVDT). Axial compressive burst fractures were created in each of ten cadaveric cervical spine specimens using a drop-weight, while force, distraction, and occlusion were monitored throughout the injury event. Pre- and post-injury radiographs and computed tomography scans compared transient and post injury spinal canal geometry changes. RESULTS: In all cases, severe compressive injuries were produced. Three had an extension component in addition to compression of the vertebra and retropulsion of bone into the canal. The mean post-injury axial height loss measured from radiographs was only 35% of that measured transiently (3.1 mm post-injury, compared with 8.9 mm measured transiently), indicating significant recovery of axial height after impact. Post injury and transient height loss were not significantly correlated (r2 = 0.230, P = 0.16) demonstrating that it is not a good measure of the extent of injury. Similarly, mean post injury canal area was 139% of the minimum area measured during impact, indicating recovery of canal space, and post-injury and transient values were not significantly correlated (r2 = 0.272, P = 0.12). Mean post-injury midsagittal diameter was 269% of the minimum transient diameter and showed a weak but significant correlation (r2 = 0.481, P = 0.03). CONCLUSIONS: Two potential spinal cord injury-causing mechanisms in axial bursting injuries of the cervical spine are occlusion and shortening of the canal. Post-injury radiographic measurements significantly underestimate the actual transient injury that occurs during impact. PMID- 8009359 TI - L4-5 degenerative spondylolisthesis in monozygous twins. AB - OBJECTIVE: The author reports symptomatic spinal canal stenosis due to degenerative spondylolisthesis at L4-5 in identical twins. SUMMARY OF BACKGROUND DATA: The patient reported his brother had a similar condition. METHODS: Monozygosity was established by phenotyping. CONCLUSIONS: Spinal morphology and degenerative disease may be genetically determined. PMID- 8009358 TI - Retained broken knife blades within the disc space. AB - STUDY DESIGN: Four cases in which, during standard laminectomies, knife blades broke deep into the disc space are reported. SUMMARY OF BACKGROUND DATA: These broken knife blades could not be removed at the time of initial operations. RESULTS: Follow-up studies indicated further anterior migration of retained fragments in two cases after ambulation. CONCLUSIONS: Because of the potential hazards of late intraabdominal visceral or vascular injuries, removal of sharp retained fragments at another session is recommended. PMID- 8009360 TI - Similar radiologic lesions of localized Scheuermann's disease of the lumbar spine in twin sisters. AB - SUMMARY OF BACKGROUND DATA: Hereditary and mechanical factors are considered to be the principal etiologic factors of Scheuermann's disease. OBJECTIVES: The authors report identical twins presenting similar lesions of localized lumbar osteochondrosis, which were worse in the one twin that practiced strenuous sports activities. CONCLUSIONS: These observations suggest, at least in some of these patients, a basic role for genetic factors in the occurrence of the disease and an influence of mechanical strain on its severity. PMID- 8009361 TI - Cellular hemangioma and angioblastoma of the spine, originally classified as hemangioendothelioma. A confusing diagnosis. AB - STUDY DESIGN: The authors report two cases of vascular tumors of the spine, classified originally as benign and malignant hemangioendothelioma, and after revision, as cellular hemangioma and angioblastomatosis, respectively. OBJECTIVES: Problems in interpretation of the confusing term hemangioendothelioma and treatment modalities for vascular tumors of the spine are discussed. SUMMARY OF BACKGROUND DATA: Hemangioendothelioma is a confusing term and is often used to cover bewilderment at the biological behavior of a vascular tumor. Its spectrum ranges, depending the references used, from benign to malignant and can mistakenly include benign lesions like cellular hemangioma and angioblastoma (solitary and multicentric). METHODS: Of two patients with a cellular tumor of the spine, the clinicopathologic data and modes of treatment are reviewed. The relevant literature is discussed. RESULTS: In the first case, the diagnosis of benign cellular hemangioendothelioma was changed to cellular hemangioma. In the second case, the original diagnosis of malignant hemangioendothelioma with metastasis to liver and lungs was changed to angioblastomatosis, most probably benign. In both cases, a correct interpretation of the initial diagnosis or proper diagnosis would have influenced the mode of treatment. CONCLUSION: Avoid the confusing term hemangioendothelioma. If a vascular lesion is benign, it should be classified as a variant of hemangioma. If malignant as angiosarcoma, use a separate category, in which lesions like angioblastoma and angioblastomatosis can be put until their nature has been clarified. PMID- 8009362 TI - Trunk strength testing with iso-machines. Part 1: Review of a decade of scientific evidence. PMID- 8009364 TI - High-frequency loss of specific immunoglobulin production in hybridoma cell lines bearing a chromosomal immunoglobulin kappa gene modified by homologous recombination. AB - We have examined the stability of trinitrophenyl (TNP) -specific IgM production in hybridoma cell lines in which homologous recombination was used to change the variable region of an endogenous chromosomal immunoglobulin kappa gene to one specific for TNP. Mutant hybridomas that have lost TNP-specific IgM production are detected with a frequency of approximately 1%. Characterization of the mutant cells reveals a variety of gross rearrangements in the recombinant kappa TNP gene as well as in the endogenous kappa and muTNP genes. PMID- 8009363 TI - Trunk strength testing with iso-machines. Part 1: Review of a decade of scientific evidence. PMID- 8009365 TI - Physical map of small cell lung cancer deletion region on short arm of human chromosome 3 (3p13-22) based on radiation fusion hybrid analysis. AB - Deletion of DNA sequences from various regions of the short arm of human chromosome 3 (3p13-14, 3p21, and 3p25) has been observed during the development of a variety of solid tumors, including lung and renal cell carcinomas. In this study we have used a set of radiation fusion hybrids to generate a physical map of chromosome 3p to orient the search for putative tumor suppressor genes. Eighty six human-hamster radiation fusion hybrids were screened on Southern blots for the retention of 55 human chromosome 3p DNA markers. The high marker density enabled us to identify a set of successively overlapping chromosome fragments in the 3p13-22 area guided by eight markers with previously known order. Twenty-four map intervals were suggested using breakpoints determined by partial fragment overlaps. The final order between the markers derived is consistent with previous information about localizations for 26 of the markers to three larger cytogenetic intervals. PMID- 8009366 TI - Region-specific microdissection library and single-copy microclones for human chromosome 2p11-p13. AB - We report the construction and characterization of a region-specific microdissection library for human chromosome 2p11-p13. This library (designated 2P4 library) is large, comprising 600,000 recombinant microclones. Thirty to 40% of the clones contain unique sequences. The insert sizes range from 100 to 800 bp, with a mean of 380 bp. A subset of the microclones was selected, based on their weak or no hybridization to total human DNA, for further analysis. Of 50 single-copy microclones analyzed, 35 clones (70%) were derived from human and are chromosome 2-specific. The insert sizes and the hybridizing genomic HindIII fragments of these clones were also determined. The 2P4 microdissection library and the single-copy microclones from the library are useful in preparing STS (sequence-tagged site) to isolate corresponding YAC (yeast artificial chromosome) or other clones with large inserts and for isolating region-specific cDNA clones as candidate genes for cloning disease-related genes assigned to this region. PMID- 8009367 TI - Identification of human chromosome region 3p14.2-21.3-specific YAC clones using Alu-PCR products from a radiation hybrid. AB - Deletion of DNA sequences from at least three different regions on the short arm of human chromosome 3 (3p13-14, 3p21 and 3p25) are frequently observed during the development of many solid tumors, including lung cancers and renal cell carcinomas. In order to physically characterize the 3p21 region, we previously identified a radiation fusion hybrid that contained about 20 megabases of DNA from chromosome region 3p14.2-p21.3. In this study total Alu-PCR products from this hybrid were used as a probe to isolate 86 yeast artificial chromosomes (YAC) clones from a 620-kb average insert YAC library (ICRF). Sixty-nine Alu-PCR markers, generated from the YACs, and seven PCR primers were used to screen for overlaps between individual clones. Seven contigs were identified encompassing 32 YAC clones. Based on previous information about localization of the PCR primers, the three largest contigs could be assigned to smaller subregions between 3p14.2 and 3p21.3. By this work a large proportion of the 3p14.2-21.3 region is covered with large-insert YAC clones. PMID- 8009368 TI - Alignment of physical and genetic maps of human 8q23-qter using somatic cell hybrid mapping panel. AB - We describe a mapping panel for the 8q23-qter region composed of human-hamster hybrid cell lines carrying deletion and translocation derivatives of human chromosome 8. The panel divides this region of the chromosome into nine intervals and has been used to map 40 loci by Southern blot hybridization and PCR. Use of this mapping panel has allowed us to align the terminal portions of two different genetic maps of chromosome 8 with each other and with the physical map of the chromosome. PMID- 8009370 TI - Mouse Huntington's disease gene homolog (Hdh). AB - The incurable neurodegenerative disorder, Huntington's disease (HD), is caused by an expanded, unstable CAG repeat encoding a stretch of polyglutamine in a 4p16.3 gene (HD) of unknown function. Near the CAG repeat is a polyproline-encoding CCG repeat that shows more limited allelic variation. The mouse homologue, Hdh, has been mapped to chromosome 5, in a region devoid of mutations causing any comparable phenotype. We have isolated overlapping cDNAs from the Hdh gene and compared their sequences with the human transcript. The consensus mouse coding sequence is 86% identical to the human at the DNA level and 91% identical at the protein level. Despite the overall high level of conservation, Hdh possesses an imperfect CAG repeat encoding only seven consecutive glutamines, compared to the 13-36 residues that are normal in man. Although no evidence for polymorphic variation of the CAG repeat was seen, a nearby CCG repeat differed in length by one unit between several strains of laboratory mouse and Mus spretus. The absence of a long CAG repeat in the mouse is consistent with the lack of a spontaneous mouse model of HD. The information presented concerning the sequence of the mouse gene should facilitate attempts to create such a model. PMID- 8009369 TI - Chromosome localizations of genes for five cAMP-specific phosphodiesterases in man and mouse. AB - Cyclic nucleotides are important second messengers that mediate a number of cellular responses to external signals. Cyclic nucleotide phosphodiesterases play a role in signal transduction by regulating the cellular concentrations of these messengers. Here, we have applied Southern analyses of somatic cell hybrid lines and of recombinant inbred (RI) mouse strains as well as fluorescence chromosomal in situ hybridization (FISH) to chromosomally localize five cAMP-specific nucleotide phosphodiesterase genes in human and mouse. Genes DPDE1, DPDE2, DPDE3, and DPDE4 that share sequence homology with the Drosophila dunce gene were assigned to human chromosome 19 (DPDE1 and DPDE2), 5q12 (DPDE3), and 1p31 (DPDE4) and to mouse chromosomes 8, 9, 13, and 4, respectively. The high-affinity cAMP specific phosphodiesterase gene (HCP1) was mapped to human chromosome 8q13-q22. Since these genes are potential candidates for involvement in psychiatric or behavioral disorders, knowledge of their chromosomal localizations will facilitate the discovery of their association with disease genes as they are being mapped by linkage studies. PMID- 8009371 TI - Isolation, characterization, and mapping of gene encoding dihydrolipoyl succinyltransferase (E2k) of human alpha-ketoglutarate dehydrogenase complex. AB - We have isolated and sequenced cDNAs representing the full-length (2987-bp) gene for dihydrolipoyl succinyltransferase (E2k component) of the human alpha ketoglutarate dehydrogenase complex (KGDHC) from a human fetal brain cDNA library. The E2k cDNA was mapped to human chromosome 14 using a somatic cell hybrid panel, and more precisely to band 14q24.3 by in situ hybridization. This cDNA also cross-hybridized to an apparent E2k pseudogene on chromosome 1p31. Northern analysis revealed the E2k gene to be ubiquitously expressed in peripheral tissues and brain. Interestingly, chromosome 14q24.3 has recently been reported to contain gene defects for an early-onset form of familial Alzheimer's disease and for Machado-Joseph disease. Future studies will be necessary to determine whether the E2k gene plays a role in either of these two disorders. PMID- 8009372 TI - [Neuromuscular diseases. The everyday admission of patients]. PMID- 8009373 TI - [Education of children on ventilators and of their family. The nurse's role]. PMID- 8009374 TI - [The overly long nights]. PMID- 8009375 TI - [Neuromuscular diseases. Psychological problems]. PMID- 8009376 TI - [The tracheal cannula]. PMID- 8009378 TI - [Rhythms and life]. PMID- 8009377 TI - [Testimony. The rage to live]. PMID- 8009379 TI - [Vitamin D. Physiological and pathological aspects and therapeutic use]. PMID- 8009380 TI - [Rites and beliefs about labor pain. Joyous pain. 2]. PMID- 8009381 TI - [The neuromuscular diseases]. PMID- 8009382 TI - [Mother-child AIDS: nursing care]. PMID- 8009383 TI - [Neuromuscular diseases. Certain genetic principles]. PMID- 8009385 TI - [Immediate and delayed complications of menopause]. PMID- 8009384 TI - [Hormonal treatment of menopause. The different products used]. PMID- 8009386 TI - [The experience of menopause. 2 or 3 things that I know about it]. PMID- 8009387 TI - [Family interactions]. PMID- 8009388 TI - [Premenopause or perimenopause. When does it start and how to treat it?]. PMID- 8009390 TI - [Nutrition for the lactating woman]. PMID- 8009389 TI - [Sudden death in the cradle. Experience of a reference center]. PMID- 8009391 TI - [Repeated vomiting]. PMID- 8009392 TI - [Principles and overview of hormonal treatment of menopause]. PMID- 8009394 TI - [Abortion, induced. Medical techniques]. PMID- 8009393 TI - [Induced abortion. Complications]. PMID- 8009395 TI - [Demand for abortion. Special aspects of drug-induced abortion]. PMID- 8009396 TI - [Demand for abortion. Detection of cervical cancer and precancerous lesions]. PMID- 8009397 TI - [Demand for abortion. Pre-abortion discussion]. PMID- 8009398 TI - [Experienced sterility with repeated abortions]. PMID- 8009399 TI - [Prevention of abortion]. PMID- 8009400 TI - [Patient admission and induced abortion. Reception by the nursing team]. PMID- 8009402 TI - [Voluntary interruption of pregnancy. The legal aspect]. PMID- 8009401 TI - [Patient admission and induced abortion. A different mode: homeopathy and sophrology]. PMID- 8009403 TI - [The approach to maternity in different cultures]. PMID- 8009404 TI - [A nose bleed]. PMID- 8009405 TI - [Voluntary interruption of pregnancy. Pre-abortion consultation]. PMID- 8009406 TI - [Induced abortion. Surgical technique]. PMID- 8009407 TI - If you are not ahead, you are behind! PMID- 8009408 TI - Tissue plasminogen activator thrombolysis and transluminal angioplasty in the treatment of basilar artery thrombosis: case report. AB - A 61-year-old man with basilar artery thrombotic occlusion was successfully treated by a combination of local infusion of tissue plasminogen activator (t-PA) followed by percutaneous transluminal angioplasty (PTA). t-PA superselective infusion combined with the mechanical destruction of the clot by the guide wire was effective for recanalization. A Stealth dilation catheter, with a 2.5-mm balloon diameter and 10-mm length, was used for PTA. A balloon inflation time of 60 seconds with 4 atmospheres of pressure was delivered for successful dilation of the basilar artery. It was confirmed to be widely patent on follow-up angiography 40 days after the combined procedure with no further ischemic attacks apparent on clinical examination at 6 months. PMID- 8009409 TI - Percutaneous transluminal angioplasty for acute stroke due to stenosis of major cerebral vessels: report of two cases. AB - The Stealth dilation catheter was introduced for the intravascular treatment of two patients with acute and unstable ischemic stroke due to hemodynamically significant stenosis in the one case of the middle cerebral artery and in the other of the vertebral artery. Cerebral perfusion study on the two cases showed a moderately low flow area in the right cerebral hemisphere and in the left cerebellar hemisphere, respectively. Percutaneous transluminal angioplasty (PTA) using the Stealth catheter was conducted. The two cases showed marked improvement in their neurologic state just after PTA with marked increase in cerebral perfusion in the relevant regions. PMID- 8009411 TI - Vascular malformations of the brain in hereditary hemorrhagic telangiectasia (Rendu-Osler-Weber disease). AB - Six patients with vascular malformation of the brain in hereditary hemorrhagic telangiectasia (HHT) were reviewed to determine clinical and radiographic characteristics of these lesions. There were two patients with arteriovenous fistula (AVF), three with arteriovenous malformation (AVM), and one with multiple AVMs associated with AVF. Seizures were the most common presenting symptom (seen in three patients), and two of them had intracerebral hematomas (ICH). In the remainder, the malformations were incidentally found in the course of evaluation of other diseases. Their locations were variable, but the majority was superficially confined to the cerebral cortex. Arterial supply was from mostly one feeding artery that was a cortical branch of either anterior, middle, or posterior cerebral artery. In six of nine malformations, the venous drainage was through a superficial cerebral vein into either the superior sagittal sinus or transverse sinus. Direct surgery was done on two patients with ICH, artificial embolization on one, and stereotactic radiosurgery on one. The cerebral vascular malformations in HHT are not infrequent, and in particular the importance of computed tomography and cerebral angiography should be recognized in patients with pulmonary AVF associated with HHT. PMID- 8009410 TI - Reversible middle cerebral artery occlusion in rats using an intraluminal thread technique. AB - We investigated the temporal profile for neuropathologic outcomes after cerebral ischemia using a rat model of reversible middle cerebral artery occlusion, where reperfusion can be introduced in nonanesthetized rats. Reperfusion was performed 1 hour to 5 hours after the occlusion. Control animals underwent permanent occlusion. The results indicate that the time window to reduce infarct volume is 2 hours, and that a > or = 3-hour duration of ischemia is sufficient to attain the maximal infarction observed after permanent ischemia. This suggests that any therapies that follow the therapeutic window will provide little benefit for transient cerebral ischemia and reperfusion injury. PMID- 8009412 TI - Spinal intramedullary cavernous angiomas: a literature meta-analysis. AB - The present report reviews 57 (out of 65) cases of spinal intramedullary cavernomas collected from the literature, plus one personal patient. Almost 70% of all patients were women. Mean age at diagnosis for women was 36.4 years, with a peak in the third decade. More than three-fourths of all women became symptomatic between the second and fourth decades, with a peak in the fourth decade. Unlike in men, cervical and thoracic lesions are almost equally represented, generally involving 1-2 vertebral levels. Mean size at diagnosis is 1.7 cm; no enlargement over time was seen. Symptoms are more frequently acute; pain and sensorimotor deficits are the usual complaints, but the clinical picture may simulate that of multiple sclerosis. The duration of history was less than 5 years in more than 80% of women. Bleeding was seen in 60% of women, with a risk of 1.6%/person-year of exposure globally. Cervical lesions have both a shorter course and increased frequency of bleeding. If not immediately recognized, repeated cycles of bleeding are the norm, with a mean interval of 39.6 months between the first and second episodes. The preoperative status was the single most important factor bearing on outcome, whereas sex, age, size, location, duration of history and extent of removal were not. Magnetic resonance imaging was diagnostic in all cases, whereas angiography was 100% negative. Surgery should not be a necessary first option, as recovery from the first bleeding is apparently fairly frequent. PMID- 8009413 TI - Dural arteriovenous fistulae involving the transverse-sigmoid sinus and foramen magnum. AB - The authors present a rare case of dural arteriovenous fistulae (AVFs) involving both the transverse-sigmoid sinus and the foramen magnum, which was treated successfully with multi-staged endovascular procedures. The transverse-sigmoid sinus, which was thrombosed proximally and distally, was occluded by transarterial embolization followed by intraoperative embolization of the sinus using platinum coils. The dural AVF involving the foramen magnum was occluded via a transvenous approach. PMID- 8009414 TI - The effects of a carotid-jugular fistula on cerebral blood flow in the cat: an experimental study in the acute period. AB - The purpose of the present study is to investigate the effects of feline carotid jugular (CJ) fistula (Spetzler's model) on cerebral blood flow (CBF) in the acute period after creation of the fistula. Using laser-Doppler flowmetry, cortical CBF was measured on the fistula side of 11 cats. Temporary occlusion and opening of the fistula led to an immediate increase and decrease, respectively, in cortical CBF. However, CBF returned to baseline within 1 minute, on average. CO2 reactivity in the closed fistula was preserved. It is suggested that cerebral hemodynamic changes due to Spetzler's CJ fistula model are minimal in the acute period after fistulization. PMID- 8009415 TI - Acetylcholine determination of cerebrospinal fluid in aneurysmal subarachnoid hemorrhage. AB - Acetylcholine (ACh) concentrations were determined serially in cerebrospinal fluid (CSF) obtained from 23 patients with aneurysmal subarachnoid hemorrhage (SAH) by high-performance liquid chromatography (HPLC) with electrochemical detection (ED). The values of CSF ACh were significantly low in the initial stage of SAH, and increased subsequently but they did not return to control values within 3 weeks. In addition, serial measurements of CSF butyrylcholinesterase (BChE) activity in 12 SAH patients showed that the activity was elevated significantly in the initial stage of SAH and returned to control levels within a week. This discrepancy in the recovery period between the ACh levels and the BChE activity in CSF indicated that significantly lower CSF ACh levels after SAH could not be attributed to plasma BChE contamination of CSF. These results suggested central cholinergic dysfunction after SAH, especially in the initial stage. PMID- 8009416 TI - Endovascular embolization and surgical excision for the treatment of cerebellar and brain stem hemangioblastomas. AB - Hemangioblastomas are histologically benign tumors that comprise 7%-10% of all posterior fossa lesions in the adult. Treatment of these lesions is often complicated by significant vascularity and difficulty of surgical resection in sensitive neural tissue, especially when the tumor has a significant solid component. We report the combined use of endovascular embolization of feeding pedicles and subsequent operative resection in two patients with solid hemangioblastomas of the cerebellum and brain stem. Preoperative embolization facilitated operative excision in sensitive neural areas and allowed complete surgical resection of tumors involving the lateral brain stem and cervicomedullary junction. Goals of preoperative embolization are control of inaccessible arterial supply and reduction of tumor vascularity. PMID- 8009418 TI - Osteochondroma of the rib: an unusual cause of paraparesis. AB - A case of extradural spinal cord compression secondary to invasion of the spinal canal by a costal osteochondroma is reported. The literature relating to osteochondromas of the thoracic region is reviewed. PMID- 8009417 TI - Giant intrasacral schwannoma: an unusual cause of lumbrosacral radiculopathy. AB - Sacral schwannoma is a rare lesion (23 reported cases) with a tendency to reach large proportions. Symptoms are back and leg pain, leg weakness, hypoesthesias, paresthesias, constipation, and incontinence. The peak incidence is between ages 30 and 50. Radiographs of the sacrum are abnormal in nearly all cases. Computed tomography and magnetic resonance imaging may reveal large lesions with bony erosion and involvement of the soft tissues. The treatment of this lesion is complete removal, which is curative. PMID- 8009419 TI - Technical modifications required to treat cervical chemodactomas with stereotactic radiosurgery. AB - This report describes the radiosurgical treatment of a high neck lesion in a patient with familial multifocal bilateral chemodactoma. The necessary modifications to standard radiosurgery are described. The advantages of this treatment modality for patients with familial chemodactoma are discussed. PMID- 8009420 TI - The joint annual meeting of North American and German skull base societies. Orlando, Florida, February 18-23, 1994. PMID- 8009421 TI - Trend in mortality from violent deaths: suicide and homicide, United States, 1960 1991. AB - Death rates from suicide and homicide have been rising since 1960 even as rates from all causes have decreased. Between 1960 and 1991, mortality from all causes among men aged 15 and over decreased from 885.1 per 100,000 population to 645.9. The suicide rates, however, increased from 16.6 to 18.7 per 100,000 and homicide mortality rates more than doubled, rising from 7.7 to 16.6 per 100,000. All three mortality rates were lower among women than among men. Deaths from all causes among women aged 15 and over dropped from 542.3 to 368.2 per 100,000; suicide rates decreased slightly from 5.0 to 4.3 while homicide rates among women rose from 2.4 in 1960 to 4.0 in 1991. Suicide rates remained the highest among men over age 75 and among women aged 45 to 54. Homicide rates were the highest among men aged 25 to 34 until 1988. In 1989 homicide rates among men aged 15 to 24 surpassed these and continue to rise at a rapid pace. Homicides among women were the highest among the age group 25 to 34. The second highest rates occurred at ages 35 to 44 through 1975 and at ages 15 to 24, thereafter. PMID- 8009422 TI - Violence in America's public schools. AB - As part of MetLife's series of annual surveys of U.S. public school teachers, the latest survey examined the perceptions of teachers, students and law enforcement officials about violence in their respective schools during 1993. Members of each group recognized violence as a problem in their schools, but the perceived magnitude of the problem differed among the three survey populations. Students reported seeing and fearing violence more than the teachers. Although the majority of teachers and students reported feeling safe in school, 11 percent of teachers and 23 percent of students had been victims of violence. The level of violence reported by teachers and the proportions who reported that weapons were regularly brought to school increased as the perceived quality of the education provided in the school decreased, as the proportion of minority and/or low income students increased, and in urban versus rural/suburban schools. Lack of parental supervision at home and lack of family involvement in school were considered major factors contributing to school violence by at least two-thirds of the teachers and 83 percent or more of the law officers. Sixty-six percent of students reported that guns/knives were carried to school primarily to impress friends or to increase feelings of importance; 38 percent of teachers thought self-protection and/or attempts to impress friends explained why students carried weapons to school. PMID- 8009424 TI - Access to health coverage. PMID- 8009423 TI - Who are the medically uninsured in the United States? AB - The Employee Benefit Research Institute (EBRI) analysis of the March 1993 Current Population Survey revealed that 38.9 million Americans had no private or public health insurance during 1992. This number was up some 2.3 million over that for 1991, an increase larger than was experienced from 1989 through 1991. The proportion of the total population without such insurance also steadily increased, rising from 14.3 percent in 1989 to 15.4 percent in 1992. In 1992, 38.5 million nonelderly Americans, or 17.4 percent of those under age 65, had no health insurance, up 4.1 million since 1989. A primary reason for the rising number of the nonelderly uninsureds was a decline in health coverage among individuals (and their families) working for small firms. Among the total U.S. population, close to 59 percent received employment-based coverage. Of the remainder, Medicare accounted for just over 13 percent of the coverage, Medicaid for just over 11 percent and individually purchased private sources other than an employer or union for almost 12 percent. The New England region had the lowest proportion of medically uninsureds (almost 12 percent) and the West South Central the highest (over 25 percent). By state, Hawaii and Connecticut reported the lowest percentage of medically uninsureds, whereas Nevada, Oklahoma, Louisiana and Texas reported the highest proportions in 1992. PMID- 8009425 TI - The widening gap between socioeconomic status and mortality. AB - Despite important declines in U.S. death rates since 1960, poor and less-educated people have not shared equally in this decline. Data from the 1986 National Mortality Followback Survey and the 1986 National Health Interview Survey were compared to data from the 1960 Matched Record Study. The data clearly show an inverse relationship between mortality and socioeconomic status. Results further indicate a widening of differences in mortality by education among both men and women aged 25 to 64. That is, the mortality differential has increased between those with higher levels of education and those with lower educational attainment. The disparity in mortality rates increased between 1960 and 1986 for both sexes. These findings focus attention on the disparity in death rates for subgroups of the population and point to the increasing need to address socioeconomic differentials to close the gap. PMID- 8009426 TI - Capillary hemangioma (infantile periocular hemangioma). AB - Capillary hemangiomas are the most common orbital tumors in children. They typically arise early in life, grow rapidly during a proliferative phase and then slowly regress in an involutional phase. The tumors may present as small isolated lesions of minimal clinical significance or as large disfiguring masses that can cause visual impairment and systemic symptomatology. Capillary hemangiomas are managed effectively by establishing a secure diagnosis, outlining the extent of the tumor, and understanding the natural history of the lesion, as well as its response to therapy. The ophthalmic and systemic manifestations of capillary hemangiomas are discussed in detail, as are the histopathology, radiologic findings, differential diagnosis, and therapeutic alternatives. PMID- 8009427 TI - Gliomas of the anterior visual pathway. AB - Gliomas of the anterior visual pathway are rare orbital lesions accounting for 65% of all intrinsic optic nerve tumors. These lesions occur principally among children in the first decade of life. They appear to be true neoplasms that characteristically show early growth, followed by stability in many patients. Visual prognosis is fair, and the outlook for life depends upon tumor location. When initially confined to the optic nerve alone, overall mortality is about 5%. Once the hypothalamus is involved, mortality rises sharply to over 50%. With involvement of the chiasm or hypothalamus, no form of therapy significantly alters the final outcome. Because of their indolent course, gliomas may be followed conservatively when confined to the optic nerve. In these cases, surgery is indicated only when blindness and pain or severe proptosis intervene. However, all such patients should be followed radiologically for evidence of posterior extension. When the chiasm is threatened, surgical excision via a craniotomy approach is warranted to prevent subsequent hypothalamic or third ventricle involvement. Malignant optic glioma is a distinct disease primarily affecting middle-aged adults. The chiasm is always involved, and although one eye may be spared initially, rapid progression to bilateral blindness is usual. The disease is uniformly fatal. PMID- 8009428 TI - Reporting adverse drug reactions: characteristics and procedures of three organizations. AB - Three organizations in the U.S.A. ask health care providers to report adverse effects of drugs in their patients: The Food and Drug Administration; United States Pharmacopoeia; and the National Registry of Drug Induced Ocular Side Effects and Drug Interactions. In a comprehensive Table, the characteristics and procedures of these three organizations are summarized. PMID- 8009429 TI - Anterior segment ischemia after strabismus surgery. AB - Surgery on the extraocular muscles of the eye is generally consisted a safe procedure which is associated with low morbidity and mortality. While infrequent, intra-operative complications occasionally occur. Tenotomy of multiple rectus muscles can result in interruption of the vascular supply to the anterior segment of the eye. Anterior segment ischemia (ASI) may result. This article reviews the complication of anterior segment ischemia as a result of strabismus surgery and its potential for producing permanent visual loss. PMID- 8009430 TI - Disk edema and peripheral neuropathy. AB - A 55-year-old woman presented with an eight-year history of progressive gait dysfunction and a 2-3 week history of horizontal diplopia. Examination of the patient revealed acute papilledema, intermittent esotropia, and upper and lower motor neuron findings in her lower extremities. CT scan of the head showed communicating hydrocephalus. A spinal cord tumor extending from T11 to L3 was visualized by MR imaging of the spine. All of her symptoms, except for a left foot drop, resolved with aggressive removal of the tumor, which was a myxopapillary ependymoma. Mechanisms of the neuro-ophthalmic picture and treatment of this syndrome are discussed. PMID- 8009431 TI - Queen Victoria, her physicians, and her cataracts. AB - Decreasing vision due to cataracts became a significant problem for Queen Victoria toward the end of the 19th century. Her personal physician, Sir James Reid, obtained consultations with two eminent British ophthalmologists, George Lawson and Edward Nettleship. The Queen was not satisfied, and requested an opinion from the German professor Hermann Pagenstecher. All the doctors agreed on the diagnosis, but the Queen never underwent surgery. PMID- 8009432 TI - [Like turning over a leaf. Continuing education. Interview by Grethe Kjaergaard]. PMID- 8009433 TI - [Only for a few. Continuing education]. PMID- 8009434 TI - [A life of research beckons. Continuing education. Interview by Grethe Kjaergaard]. PMID- 8009435 TI - [A life style of research. Continuing education. Interview by Grethe Kjaergaard]. PMID- 8009436 TI - [The important word. Continuing education. Interview by Grethe Kjaergaard]. PMID- 8009437 TI - [Here you can look for funds. Continuing education]. PMID- 8009439 TI - [Here they go on. Continuing education]. PMID- 8009438 TI - [The most important aspect to remember]. PMID- 8009440 TI - [Now it is enough]. PMID- 8009441 TI - [The eye of the needle. Continuing education]. PMID- 8009442 TI - [Back to practice. Continuing education. Interview by Grethe Kjaergaard]. PMID- 8009443 TI - [Needing more than we believe. Continuing education. Interview by Grethe Kjaergaard]. PMID- 8009444 TI - [Clinical nursing. Following a heart infarct]. PMID- 8009445 TI - [Senile dementia--a relative]. PMID- 8009446 TI - [Work environment. The most stressful work. Interview by Mette Fjordbo]. PMID- 8009447 TI - [Overcrowding]. PMID- 8009448 TI - [Patient Complaint Tribunal. Carelessness with drugs]. PMID- 8009449 TI - [Patient Complaint Tribunal. Use those plaintiffs. Interview by Kirsten Bjornsson]. PMID- 8009450 TI - The pangs of prophets. OK, so now we know the future. What do we do about it? PMID- 8009451 TI - Researchers issue glowing report on calcium's effect in blood vessels. PMID- 8009452 TI - RBRVS revisited. Midterm report card shows Medicare payment system still has problems. PMID- 8009453 TI - What Texans think about their physicians. A new study gives a close-up look at the issues behind the declining image of the medical profession. PMID- 8009454 TI - How patient-friendly is your office? PMID- 8009455 TI - Doc Hollywood, beware. Recent laws further restrict advertising by physicians. PMID- 8009456 TI - Seeing a lion at the mouth of the cave. How physicians in high-risk specialties cope with stress. PMID- 8009457 TI - The lives of female physicians. AB - Survey data from 113 female physicians, 634 male physicians, and 41 female dentists were compared. Instruments designed to assess work satisfaction, work stress, marital satisfaction, family competence, and psychiatric symptoms and treatment were used, thereby exploring important life domains concurrently. The results suggest that female physicians are much more like both male physicians and female dentists than anticipated. Generally, female physicians describe high levels of work satisfaction, moderate levels of work stress, average-to-high levels of marital satisfaction, and relatively low levels of psychiatric distress. Their lower levels of practice income remain something of an enigma as gender remains the most powerful predictor of income and is not replaced in statistical analyses by specialty, hours worked, or other significant variables. Finally, female physicians who find higher levels of satisfaction in work also report higher levels of marital satisfaction and fewer psychiatric symptoms. For these women, a highly satisfying medical career does not apparently need to be experienced at the cost of marital or personal distress. PMID- 8009458 TI - Adolescent health needs and access to care in the Army medical system. AB - The United States Army Medical Department operates one of the largest comprehensive medical care systems. Health of adolescents is promoted by providing them with access to care without the impediment of direct monetary charge. This study defines the scope of health concerns and the availability of care for the common health problems of adolescents in this geographically widespread medical care system of high accessibility. In addition to common respiratory illness, more age-group-unique musculoskeletal, psychosocial, dermatologic, gynecologic, and sexuality-related problems are noted. Availability of care varies by location, with tertiary centers providing more services appropriate to developmental stage. These data are useful in planning improved health-care services appropriate to developmental stages of adolescents in the Army medical system as well as in other health-care systems. PMID- 8009459 TI - In Tennessee, rural health clinic reimbursements cut. PMID- 8009460 TI - Hospice model shows how managed care can succeed. PMID- 8009461 TI - Mystery in Cameron County. Physicians and health officials search for cause of high rate of anencephaly in the Rio Grande Valley. PMID- 8009462 TI - Deselection, round two. TMA takes due process fight with managed care organizations to US Congress. PMID- 8009463 TI - Balancing act. Getting the right mix of payor types is crucial in today's market. PMID- 8009464 TI - The emergence of Texas biotech. PMID- 8009465 TI - "But I (cough) don't feel (cough) sick." Legal remedies for tuberculosis patients who won't take their medicine. PMID- 8009466 TI - Tommy Love, DO. Adventurer tries to solve aviation mystery. PMID- 8009467 TI - Diagnosis and treatment of acute scaphoid fractures. PMID- 8009468 TI - Women changing world of surgery. PMID- 8009469 TI - Organized medicine: play ball. PMID- 8009470 TI - Campaign under way to prevent adverse drug interactions. PMID- 8009471 TI - [Unscientific use of scientific data?]. PMID- 8009472 TI - [Drinking water and health]. PMID- 8009473 TI - [Addictive drugs in road traffic]. PMID- 8009474 TI - [Abuse of doping preparations outside organized sports. A new challenge for health care]. PMID- 8009475 TI - [Endocrine effects of doping with androgenic anabolic steroids]. AB - We describe two case histories that highlight some of the endocrine effects of doping with androgenic anabolic steroids. The main endocrine effect observed after use of androgenic anabolic steroids is the development of hypogonadotrope hypogonadism, characterized by low levels of gonadotrophins, suppression of testosterone production and azoospermia. If testosterone is used alone, or in combination with synthetic anabolic steroids, the circulating levels of testosterone are normal or high. Oestrogen levels may be elevated owing to aromatization of testosterone. The level of sex hormone binding globulin is suppressed. These endocrine parameters are of practical use in evaluating patients misusing androgenic anabolic steroids. PMID- 8009476 TI - [Driving under the influence of alcohol, drugs and narcotics]. AB - The National Institute of Forensic Toxicology has registered a large increase in the number of samples from drivers suspected of driving under the influence of drugs other than alcohol. Illegal and prescribed drugs are detected in an increasing number of cases. In many of these cases, the drugs are combined with alcohol. The most frequent drugs detected in 1992 in addition to alcohol were tetrahydrocannabinol (the psychoactive compound in cannabis) and benzodiazepines, mostly detected at blood concentrations above therapeutic levels. Simultaneous use of different benzodiazepines and use of benzodiazepines in combination with illegal drugs are common. The number of samples containing amphetamine showed a significant increase in 1992 compared with 1991 (an increase of 80%). PMID- 8009477 TI - [Neuromuscular disorders of the extremities after heroin-induced rhabdomyolysis]. AB - We describe four patients with neuromuscular deficiencies after heroin-induced rhabdomyolysis. Such deficiencies have a good prognosis, but all our patients continued to have sequelae. In an emergency situation one should always consider fasciotomy for acute compartment syndromes. Two of our patients developed a Volkmann's ischemic contracture after acute compartment syndromes. The other two had deficiencies from compression neuropathies. We observed functional restitution over a period of one to two years. Physiotherapy and orthopaedic aids are important in the rehabilitation of these patients. However, the main problem is still their drug addiction. PMID- 8009478 TI - [Cigar-like oxalate crystals in ethylene glycol poisoning]. AB - Coma with grave metabolic acidosis, increased anion and osmolal gap, oxalate crystals in urine sediment and increased ultrasound density of the renal parenchyma are essential clues to the diagnosis of ethylene glycol poisoning. Envelope-like dihydrate calcium oxalate crystals are usually found in the sediment of these patients. We describe a patient with needle and cigar-shaped monohydrate calcium oxalate crystals in urinary sediment, but no detectable ethylene glycol in blood tests taken upon arrival at hospital 12 hours after ingestion. The patient was treated with alkali and haemodialysis, and recovered without any sequelae. Monohydrate calcium oxalate crystals were an essential clue for diagnosis of ethylene glycol poisoning in this patient. PMID- 8009479 TI - [Iron status in postmenopausal women]. AB - Iron intake was determined in 42 postmenopausal women from food records over two three-day periods, with weighing of the food. The average daily intake was 9.4 mg (95% confidence interval 8.8-9.9). In 70% of the women the intake was lower than the nationally recommended 10 mg per day. Serum-ferritin was measured to detect possible iron deficiency. The average serum-ferritin was 60 micrograms/l (95% confidence interval 47-72). Only two women were advised to take iron supplements. One of these women had a serum-ferritin below 12 micrograms/l, which is regarded as empty iron store. A low iron intake in postmenopausal women is not an indication to prescribe iron supplements. Iron deficiency can be assessed only by serum-ferritin measurements. PMID- 8009480 TI - [Idiopathic osteoporosis in middle-aged men--a "new" disease?]. AB - Idiopathic osteoporosis is uncommon in middle-aged men. We discuss nine otherwise healthy men aged from 35 to 57 years, eight of whom were shown to be osteoporotic when subjected to detailed investigation because of back pain. None had suffered fractures of the appendicular skeleton as adults. All had an ordinary life style and ate a normal diet. Lumbar spine bone density was greatly reduced in all nine patients, while six of them showed normal values for cortical bone density in the forearm. Bone histomorphometry showed high turnover of bone tissue, with high bone resorption and lower than average bone formation. Serum osteocalcin levels were low in all nine patients, but alkaline phosphatase was higher than the upper normal limit in six of them. The etiology of the disease is unknown, but the pathogenesis is a result of disparity between formation and resorption of bone tissue. Unidentified environmental factors may be one of the reasons for the appearance of idiopathic osteoporosis as a "new" disease among middle-aged men. PMID- 8009481 TI - [Health effects of physical activity and psychological training]. AB - Skeletomuscular pain is a very frequent complaint. Most patients recover spontaneously, but in some this pain may become long-lasting or even chronic. This occurs only in a minority, but even so skeletomuscular pain is the most frequent reason for long-term sickness benefit and permanent disability in the present Norwegian population. This report reviews the results of a series of controlled studies in Norway demonstrating that such pain may be treated by several different methods. Positive effects have been demonstrated from aerobic physical training, stress management training, relaxation training, and combinations of these programmes. Interventions directed at the organisation of the work situation have also had positive effects. These effects include decrease of pain and of psychological and subjective health complaints. However, a comparison of the effects of the different types of treatment would have to be based on a large multicentre study. PMID- 8009482 TI - [Carbohydrate-deficient transferrin--a reliable marker of high alcohol consumption?]. AB - Carbohydrate deficient transferrin has been proposed as an important marker for alcohol abuse. Using isoelectric focusing and two different radioimmunoassays we measured carbohydrate deficient transferrin throughout an alcohol withdrawal period in ten abusing men. Values within the normal range were found in two to four individuals, depending on the method. Nevertheless, carbohydrate deficient transferrin was more frequent pathologically (in two out of three methods) than any other of the common markers (glutamyl transferase, alanine transferase, aspartate transferase, mean corpuscular volume). During the withdrawal period, the carbohydrate deficient transferrin value increased in two patients after a new alcohol intake. However, it also increased on other occasions when a new alcohol intake was highly unlikely. Therefore, a single test or even repeated tests of carbohydrate deficient transferrin may give a wrong conclusion. Since the cost of the analysis is high, the clinical benefit should be evaluated more closely before the test is used in pure clinical settings. PMID- 8009483 TI - [Potassium channel openers. A new possible therapeutic principle in several diseases]. AB - Potassium channels are ion channels in the cell membrane which are especially important for regulation of the membrane potential and the cell's excitability. Potassium channel openers are drugs that interfere with these channels, and several such substances have been developed. Existing substances show highest affinity to vascular smooth muscle. The clinical effect is relaxation of blood vessels resulting in lower blood pressure. However, current efforts are concentrated on finding substances which are selective for other cell types. Possible areas of application are treatment of hypertension, angina pectoris, arrhythmias, asthma and urinary bladder instability. PMID- 8009485 TI - [From clinical trials to routine treatment. What factors are decisive for implementation of research results into clinical practice routines?]. AB - In the second of two articles the author discusses non-scientific factors that influence the application of results from clinical research in clinical practice. This step is essentially a matter of judgement. The factors considered include selective use of research results, protection of special interests, the impact of the "last case", the therapeutical imperative and consensus conferences. Attention is drawn to the importance of market leaders and the relationship between scientists and the pharmaceutical industry. The absence of price incentives is underlined. It is pointed out that clinical research is a vital element in the long-term efforts to secure high quality service to patients. PMID- 8009484 TI - [From clinical trials to routine treatment. General aspects of clinical trials in cardiovascular diseases]. AB - The first of two articles deals with general aspects of clinical cardiological research: hard end points -mortality and morbidity-in relation to intermediate end points, power of clinical studies, multicentre studies, meta-analyses, and the relationship between the trial population and the total patient population. The article takes up the kind of problems that are addressed in clinical research, and the relationship between the medical profession and the pharmaceutical industry. The author discusses the situation as regards clinical research in Norway, and emphasizes the need for greater efforts in this field. PMID- 8009486 TI - [Antihypertensive treatment and risk of coronary disease. How significant is the antihypertensive effect for metabolic factors?]. AB - A recent meta-analysis of hypertension treatment trials showed a marked reduction in cerebrovascular disease and a less pronounced reduction in coronary heart disease. Treatment has consisted of diuretics and betablockers, and this paper discusses the possible influence of their metabolic side effects as compared with the new vasodilating agents (angiotensin converting enzyme inhibitors, alpha receptor antagonists and calcium channel blockers). Several studies have now been started to compare the effect of these compounds with diuretics and betablockers with respect to long-term cardiovascular morbidity and mortality. Until the results of these studies are available, young patients (i.e. < 60-65 years) at high risk of coronary heart disease, especially patients with the insulin resistance syndrome or diabetes mellitus, should in our opinion be treated with ACE-inhibitors, alpha receptor blockers or calcium channel blockers. PMID- 8009487 TI - [Drug risk intervention--a care technology in crisis?]. AB - Drug treatment in patients who feel well but have an elevated risk of disease and premature death is steadily increasing. This kind of treatment is qualitatively different from the ordinary practice where patients visit a doctor because of symptoms or complaints. In recent decades, great confidence has evolved in this kind of risk intervention. Antihypertensive treatment is one example and risk intervention with drugs is also used in cases of hypercholesterolemia, type 2 diabetes and osteoporosis. The effect of this effort on public health has not been as great as expected. This kind of treatment has emerged gradually and without debating the principles. The author wants to start a debate about what kind of treatment we are experiencing. Is it quasi-treatment based on the premises of the technology? Should we think again about this kind of practice? The author suggests subjects for further debate, including the use of precise language, better co-operation with the persons at risk and further research. PMID- 8009488 TI - [Diclofenac in the treatment of pseudo-croup]. PMID- 8009489 TI - [Use of condoms prevents sexually transmitted diseases]. PMID- 8009490 TI - [Environmental health protection]. PMID- 8009491 TI - [About temptation to dishonesty in scientific research]. PMID- 8009492 TI - [About a comprehensive pseudonymous registry]. PMID- 8009493 TI - [Surveys in occupational dermatology]. PMID- 8009494 TI - [Diagnosis and treatment of acute bronchitis]. PMID- 8009495 TI - [Abdominal aortic aneurysms]. PMID- 8009496 TI - [Abdominal aortic aneurysm at a county hospital]. AB - During the period January 1985 to May 1993, 129 patients were hospitalized for abdominal aortic aneurysms at the hospital in Haugesund. Of these patients, 93 underwent surgery at our hospital. Acute operations were performed in 33 patients with a perioperative (30 days) mortality of 45%. 60 patients underwent elective surgery with no perioperative (30 days) mortality. 14 patients were sent to a regional/university hospital. For various reasons, 22 patients were not operated on. PMID- 8009497 TI - [Cystic lymphangioma of the mesentery]. AB - Cystic lymphangioma of the mesentery is a rare congenital lesion with a relatively low growth potential. It is typically found in young adults, and thereby excluded from other, more aggressive lymphatic malformations seen in newborns. Symptoms of onset may be dramatic and sudden, but are often preceded by an interval of diffuse abdominal discomfort, possibly associated with loss of weight and a palpable abdominal mass. The multicystic architecture of the lesion is clearly visible on an abdominal CAT-scan and indicates the diagnosis. Percutaneous drainage of the cysts has neither diagnostic nor therapeutic effects. Radical excision of the expansion may include resection of the related intestinal segment. Lymphangioma of the mesentery is not malignant. We suggest an ultrasound follow-up six months after the intervention to establish whether the surgery has been successful. PMID- 8009498 TI - [Campylobacter infection. Epidemiology, risk factors and preventive measures]. AB - Campylobacter bacteria are a significant cause of diarrhoea in Norway. This article reviews aspects of epidemiology, risk factors, and prevention of the disease, with special emphasis on a case-control study conducted in the Oslo region. The results indicate that the following preventive measures are likely to have the greatest impact on the occurrence of the infection: (a) providing consumers with drinking water of adequate hygienic quality, (b) good hygienic practices when in contact with dogs and cats, (c) good kitchen hygiene during barbecues and when handling and preparing poultry, especially poultry purchased abroad (d) preventing import of contaminated food products, (e) reducing the level of Campylobacter colonization in poultry flocks, and (f) educating consumers about how infection can be avoided when travelling abroad. PMID- 8009499 TI - [Angioedema associated with ACE inhibitors]. AB - Angio-oedema as an adverse effect of angiotensin converting enzyme-inhibitors (ACE-inhibitors) is reported to occur in one to two of 1,000 treated patients per year. This estimate may be too low, since the swelling of face, lips, tongue and throat is very often attributed to food allergy. Furthermore, attacks of oedema may occur after months or even years of ACE-inhibitor treatment, thereby obscuring the link to the medication. This adverse effect is non-immunogenic. The oedema is explained by local enhancement of bradykinin, which under normal circumstances is broken down by angiotensin converting enzyme. The question of what makes some people vulnerable is still unsolved. The oedema can develop quickly and may lead to suffocation. In many cases, conventional antiallergic treatment in the form of steroids, antihistamines and epinephrine has inadequate effect. Intubation of the larynx may be necessary, but can be extremely difficult in the case of massive glassy oedema. Involvement of the neck can sometimes hinder tracheotomy, making early intervention essential. The authors describe two patients with moderate swellings, and discuss a potential, yet experimental, use of C1-inhibitor concentrate in the treatment of ACE-inhibitor provoked angioedema. PMID- 8009500 TI - [Psychogenic muscular activity as a risk factor of muscular pain]. AB - Recent research indicates that any continuous load on the shoulder and upper limb muscles is a risk factor for occupational muscle pain. When the muscle load is moderate to low, the duration seems far more important than the actual load level, possibly because of a fixed recruitment order of motor units. Research at the Norwegian National Institute of Occupational Health has shown that a mentally challenging task at a visual display terminal may give a low level of muscle activation with apparently no purpose as regards posture or movement ("psychogenic" muscle tension), based on continuous firing in a few motor units. This indicates a possible mechanism for the often observed link between psychosocial stress and muscle pain. PMID- 8009501 TI - [ADP-registration of patients with contact dermatitis at the Ulleval hospital. A 1-year material]. AB - Databases for monitoring patients with contact dermatitis have become indispensable for managing a constantly increasing variety of products which cause allergic and toxic dermatitis. As a result of collaboration between the Department of Dermatology and Department of Information Technology, Ulleval Hospital, we now have developed a database for registering patients with occupational dermatitis. The programming tool is DataEase, which contains files for the patients' personal data, site of the dermatitis, results of tests and diagnosis. PMID- 8009502 TI - [Acute bronchitis in adults. Clinical findings, microorganisms and use of antibiotics]. AB - Among 72 adult patients with a diagnosis of acute bronchitis, serological investigation established the presence of an aetiologic agent in 29 (40%). Influenza virus was the most common pathogen. Seven patients had bacterial infection, caused by pneumococci in four patients and Mycoplasma pneumoniae in three. Five of the patients had pneumonia as diagnosed by radiography, and mycoplasmal aetiology was established in one of these. Altogether, 11 patients either had bacterial infection or radiographic pneumonia. Although the doctors' recording of wheezes was strongly associated with prescription of antibiotics (p < 0.0001), wheezes were heard only in two of the 11 patients with pneumonia or bacterial infection, compared with 30 of the 61 patients with viral or unspecified bronchitis. The median value of C-reactive protein (CRP) was 52 mg/l in the 11 patients, significantly higher than < 11 mg/l in the 61 other patients (p < 0.0001). The corresponding values for erythrocyte sedimentation rate were 45 and 14 mm/h (p < 0.0005). The results indicate that certain patients with acute bronchitis should be treated with antibiotics, and that the erythrocyte sedimentation rate and the CRP-test may be useful in detecting which patients this applies to. PMID- 8009503 TI - [Group B streptococci in pregnancy--guidelines for routine examinations and treatment. American Academy of Pediatrics]. AB - Group B streptococci are a major cause of serious infections in the newborn, and also cause chorioamnionitis, late abortions, puerperal infections and sepsis. Group B streptococci are harboured in the genital tract of 5-40% of pregnant women, and 50-70% of their infants are colonized. Severe perinatal infections caused by group B streptococci affect 1-5 infants per 1,000 live births. American Academy of Pediatrics (AAP) have issued guidelines for preventing group B streptococcal infections. These are described, and it is suggested that these should be adopted in Norway. PMID- 8009504 TI - [ICPC diagnoses in 60 offices of general practitioners]. AB - The new classification system ICPC was used by 60 general practitioners to record consulting room encounters during one week. The study focused on unemployed and marginalized patients, and provided experience in the use of ICPC shortly after the system was made mandatory by National Insurance Administration. One to five months afterwards, 85% of the GPs used ICPC fully and 10% to some extent. We had no problems in coding the remaining text diagnoses, nor in recoding to the chapters of the diagnostic system ICHPPC. A quarter of the main diagnoses concerned the component of symptoms. Within the problematic chapters of psychiatric and musculosceletal illnesses, the doctors applied diagnoses of symptoms and diseases to very varying degrees. ICPC makes it possible to exclude gender-related causes for the consultation. Consequently, the gender differences in the distribution of components and chapters virtually disappeared. The female surplus among the patients was reduced to 10%, of which 6.5% can be attributed to the larger share of women among the elderly. Thus, ICPC seems to be a useful tool in epidemiology. PMID- 8009505 TI - [Etiology of diabetic microangiopathy. Is the glucose level everything?]. PMID- 8009506 TI - [How do we establish patients' rights?]. PMID- 8009508 TI - [Lots of health for the money]. PMID- 8009507 TI - [Disease and security]. PMID- 8009509 TI - [Health education in connection with consultation--is the change of behavior the only goal?]. PMID- 8009510 TI - [Gene therapy--promising possibilities]. PMID- 8009511 TI - [AIDS in Africa can be conquered]. PMID- 8009512 TI - [Clinical research, teaching and quality assurance in an electronic network]. PMID- 8009513 TI - [Infrastructure for clinical research in a hospital]. AB - Clinical research in hospitals involves many partners. In Norway, the doctors are allocated little time for clinical research. Furthermore, complicated laws and directives have to be followed. The authors describe the organisation of clinical research and a software collection, including CD-ROM. We conclude that clinical research in large hospitals demands both a strong organisation and extensive use of modern information technology. The problems can be solved at acceptable cost. PMID- 8009514 TI - [Sexually transmitted diseases, HIV infection and AIDS in Mudzi, Zimbabwe. A study of knowledge, attitudes and practice in a rural area in southern Africa]. AB - We describe a study conducted in a rural area of Zimbabwe. We examined all patients who attend for treatment of a presenting sexually transmitted disease for a period of one month in 1989 and 1992. In addition we studied the knowledge of, attitudes towards and practices as regards HIV-infection and AIDS in 1992. The annual rate of sexually transmitted diseases was not different in the two periods studied. Most of the females with symptoms of sexually transmitted diseases were married and had been infected by their husbands. Most males too were married, but had been infected by prostitutes. There was a reduction in the proportion of patients who were employed as teachers, policemen or in the army. The use of condoms seems to have increased. Males were generally better informed about HIV-infection and AIDS than females were. As much as 26% of the females and 40% of the males had a close friend/relative who had died from AIDS and 69% of the females and 81% of the males had found it necessary to change their sexual behaviour after hearing about AIDS. Most people knew the most important parts of transmission, and about condoms as a means of protection, but the rate of sexually transmitted diseases remains very high. New strategies are needed in the preventive work. PMID- 8009516 TI - [Determination of estrogen receptors in aspirates from needle biopsies of breast carcinomas. Correlation to a biochemical method]. AB - Several methods exist for determining oestrogen receptor status in breast carcinomas. Biochemical methods have been widely used for many years, but recently immunocytochemical methods have become available. We have compared the outcome of the biochemical and immunocytological analysis in 274 breast cancer patients. Fine needle aspirates from all the patients were investigated immunocytologically and 214 tumours were positive (78%) and 60 negative (22%). Biochemical data were available in 155 patients, and the concordance between the two methods was 88%. Most of the 119 carcinomas (43%) that were only investigated cytologically were too small to allow both histological and biochemical analysis. A minority of patients were not operated on because of high age, and/or impaired health, or because the tumour was inoperable. In our opinion, biochemical and immunocytological methods are equally sensitive and specific in detecting oestrogen receptor in breast tumour tissue. In fine needle aspirates there is the additional advantage of morphological assessment of malignant nuclei and the possibility of obtaining material from small lesions. PMID- 8009515 TI - [HIV-prevalence in Mutoko, Zimbabwe. A study among pregnant women and patients with sexually transmitted diseases]. AB - The Ministry of Health and Child Welfare in Zimbabwe has carried out a number of surveys in different districts of Zimbabwe to determine the extent of the HIV epidemic. In Mutoko district such a study was carried out to determine the HIV prevalence among pregnant women and patients with sexually transmitted diseases. The results show that 25% of the pregnant women were HIV-positive. The highest prevalence is found among women between 25 and 30 years, and women who were pregnant for the second or third time, where more than 35% were HIV-positive. Of the patients with sexually transmitted diseases, 50% were found to be HIV positive. The HIV-prevalence was higher among men than among women, and higher among single patients than among married patients. For patients who had genital ulcers the HIV-prevalence was 67%. PMID- 8009517 TI - [Genetic disease in general practice. An interview study among general practitioners in Oppland and Oslo]. AB - We interviewed 51 Norwegian general practitioners selected at random about their knowledge and practice of medical genetics. Of these doctors, 29 worked in Oslo and 22 in Oppland county. About 90% of the doctors working in Oslo knew where to refer patients for genetic counselling, while 55% of the doctors working in the area outside Oslo had this knowledge. We believe that this difference is because Oslo has a municipal genetic clinic and is the only area in Norway with an adequate genetic counselling service according to WHO standards. This article presents the results from this survey, and discusses genetic diseases in general practice and the organisation of medical genetic services in Norway. PMID- 8009518 TI - [Causes of serious mental disorders]. AB - It is accepted that both genetic and environmental factors are important in the genesis of schizophrenic disorders, but we have little understanding how they interact to produce the illness in a given individual. The position with regard to severe affective disorders is somewhat different, since bipolar disorders seem to have a comparatively high genetic loading as against a greater influence of environmental factors in unipolar disorders. Recent research shows a significant overlap between schizophrenic and affective disorders, both for symptoms in individual cases and for family incidence of the disorders. One way of achieving better understanding of the interaction of genes and environment in the two sets of disorders is to study samples of twins and of adoptees. In such studies the chances of successful results are increased by investigating samples that are as large as possible and contain a broad spectrum of psychiatric diagnoses. PMID- 8009519 TI - [Psychiatric disorders among nurses admitted to a psychiatric clinic]. AB - During 1985-89, 82 female and 13 male nurses were hospitalized in a psychiatric clinic, Modum Bads Nervesanatorium. The frequency of personality disorders and of drug and alcohol abuse, seems to be higher among male than among female nurses. The female nurses have been compared with a sample of assistant nurses and teachers of the same sex. There were no significant differences between the three groups as regards various demographical and clinical factors. PMID- 8009520 TI - [Treatment of chronic musculoskeletal pain. Physical training and group discussions in general practice]. AB - Treatment of chronic musculoskeletal pain is a challenge. 16 female patients with problems of this kind underwent a 12 week course of treatment consisting of selected physical exercises and group discussions. Twice a week a physiotherapist led indoor training to music with this group. The discussion group, which met once a week, was led by a doctor. All the participants completed the treatment. The results of the treatment were evaluated by means of talks with the patients, observation, an assessment form and five questionnaires. The participants were examined three months before treatment commenced, and immediately before and after the treatment period. The patients profited by the treatment. They expressed this opinion spontaneously during training, on the assessment form and during group discussions. It was also noticeable to us. This impression was confirmed by reduced experience of pain measured by visual analogue scale and enhanced well-being assessed by General Health Questionnaire. Exercise improved the physical condition of the participants and also induced a positive attitude to physical activity. Mutual support and the sharing of common experiences were important factors in the discussion group. PMID- 8009522 TI - [Metformin reevaluated--time for rehabilitation?]. AB - The consumption of metformin in Norway is low. Most probably this is caused by poorly based impressions of small effects and frequent and serious side effects. A review of the literature shows that metformin and sulfonylurea lower average blood glucose values equally well, both in obese and non-obese type 2 diabetic patients. In sulfonylurea failure, addition of metformin lowers the glucose values to the same extent as a shift to insulin monotherapy does. Metformin is anti-hyperglycaemic only, and therefore does not cause hypoglycaemia. The risk of drug-related deaths is no higher with metformin than with sulfonylurea. Metformin improves the lipid profile, and has other effects which could lower risk of cardiovascular complications. The place of metformin in the treatment of type 2 diabetic patients should be reconsidered. PMID- 8009521 TI - [Gene therapy. Methods and applications]. AB - Modern techniques in molecular biology and cell biology will probably make gene therapy, i.e. therapeutic transfer of genes to the patient's cells, available for treatment of many genetic diseases, cancer, cardiovascular diseases and infectious diseases. For genetic diseases the treatment will involve the transfer of a functional copy of the defect gene. The strategy for treatment of cancer may include the transfer of genes that induce the death of cancer cells via toxic molecules, and genes that enhance the immune response to tumour cells. After several years of preclinical studies, the National Institutes of Health in the USA has, up to February 1994, approved 56 protocols for clinical trials in human gene therapy. Most of the protocols include use of viruses to aid gene delivery. This paper briefly reviews the scientific basis for gene therapy, and discusses some clinical applications of somatic gene therapy in humans. PMID- 8009523 TI - [Low frequency electromagnetic fields in the working environment--exposure and health effects. Elevated risk of cancer, reproductive hazards or other unwanted health effects?]. AB - The authors describe the physical properties of low frequency electromagnetic fields and occupational exposure to such fields in different working environments. They discuss possible health effects reported in the literature. It is concluded that there seems to be elevated risk of leukemia and brain tumours among persons employed in "electrical work", though there is insufficient evidence that the fields are responsible. No conclusion can be drawn as to risk of adverse outcome of pregnancy. When this is technically and economically feasible, exposure to low frequency electromagnetic fields should be kept to a minimum. PMID- 8009524 TI - [Occurrence of senile dementia among elderly in need of support in the municipality of Grimstad]. AB - The background for this study is the common belief in the community of Grimstad that aluminium is related to dementia; the high aluminium content in the local water supply is an ongoing source of concern. In this study we show that the prevalence of dementia among elderly in Grimstad is not higher than in the city of Bergen. We also discuss the demands the community must meet to care for the growing population of demented elderly. PMID- 8009526 TI - [When the supposedly best becomes an enemy of the good. Thoughts on disadvantages of specialization]. PMID- 8009525 TI - [Experiences and strategies of AIDS preventive work in Mudzi and Mutoko. Experiences from 2 rural districts in Zimbabwe]. PMID- 8009527 TI - [Children with asthma and treatment with steroid inhalation]. PMID- 8009528 TI - [Chloramphenicol eyedrops in acute bacterial conjunctivitis]. PMID- 8009529 TI - [Screening for early diagnosis of prostatic cancer]. PMID- 8009530 TI - [Use of syringes for dosing of drugs for peroral use and inhalation]. PMID- 8009531 TI - [Acute bronchitis, is it possible...?]. PMID- 8009532 TI - [A debate about and quality assurance of local projects]. PMID- 8009533 TI - [A pseudonymous registry of diseases and injuries--worse than nothing?]. PMID- 8009534 TI - [About linguistic equality]. PMID- 8009535 TI - [Priority decisions in hospital departments]. PMID- 8009536 TI - [Why have certain groups of physicians lost their patients' confidence?]. PMID- 8009537 TI - [Epidemiology and control of lung worm infections in cattle]. AB - The epidemiology and control of lungworm infections in cattle are reviewed. A short introduction is given on the prevalence of lungworm infections and lungworm disease. Thereafter important aspects of the life cycle, the causes of primary infections, the possible causes of outbreaks of lungworm disease and the predictability of lungworm disease are reviewed. Finally different control measures for lungworm disease, vaccination, strategic anthelmintic treatment, vigilance and anthelmintic treatment and grazing management are discussed. It is concluded that vaccination is still the best preventive method. PMID- 8009538 TI - [Campaign against swine vesicular disease]. PMID- 8009539 TI - [Corticosteroids in practice]. PMID- 8009540 TI - [Certification and commercial activities--'are the results rewarding?']. PMID- 8009541 TI - [The characteristics of stabbing-cutting injuries with a 2-phase insertion of the blade]. AB - The mechanism of formation of angular cut injuries is described, in which the blade is first partially stuck in in one plane (phase 1) and then plugged at some angle to it (phase 2). It is not enough to know the length of the main incision to make a judgement on the width of the blade of injuring instrument; identification signs should be searched both in the first and second incisions. PMID- 8009542 TI - [An analysis of traumatism with fatal outcome in the agricultural industry]. AB - The authors state a high rate of mortality due to accidents in agroindustrial production, with the maximum death rate observed in construction. Accidents with lethal outcomes most frequently occurred due to causes of a private nature and violation of regulations. Men become victims of such accidents 23 times more frequently than women. Alcoholic intoxication of the victim was a frequent cause of death, responsible for 41.2% of lethal outcomes. Transport means were the immediate cause of occupational injuries with a lethal outcome in 57.7% of cases, other frequent causes were drowning and electric current exposure. Mechanical traumas with multiple injuries and injuries to the head predominated in the structure of lethal outcomes. PMID- 8009543 TI - [The results of the simultaneous explosion of the Zaria and Plamia special grenades]. AB - New light-and-sound shells Zaria and Plamia used by operative workers of organs of the Ministry of Home Affairs of Russia are characterized by all properties typical of explosives. If they are improperly stored and subjects who should not have access to them handle them, explosions may occur involving destruction of buildings and injuries to people with all signs typical of an explosion (exposure to blast shock wave, high temperature, secondary bodily injuries). Forensic medical examination of subjects dead from explosion revealed extensive thermal burns, ruptures of viscera, craniocerebral injuries, separation and crushing of the limbs, bruises, abrasions, wounds caused by fragments of building and articles in the rooms. PMID- 8009544 TI - [The differentiation of acute coronary failure and asphyxia as the causes of death]. AB - A death case is described caused by acute coronary failure due to atherosclerotic involvement of heart vessels. Death occurred suddenly during compression of the thorax with the hands of a strong young man. Initial forensic medical expert evaluation came to a conclusion that death ensued from asphyxia resultant from thorax compression. Repeated expert evaluation considered thoracic compression as a factor conducive to death. PMID- 8009545 TI - [The use of the polymerase chain reaction method for the analysis of polymorphic sections of the human genome in performing forensic medical expertise on material evidence]. AB - The method of expert evaluation is described which was carried out to define the appurtenance of seminal spots to one of two suspected subjects. Biological sample appurtenance was identified using genetic markers by analysis of allele status of loci containing variable numbers of tandem repeats. Two loci were analyzed, ApoB and IL-6. To determine the studied loci alleles polymerase chain reaction with the DNA isolated from material evidences used as the matrix was used as well as agarose gel electrophoresis. Analysis helped determine appurtenance of seminal spots to suspected subject V. PMID- 8009546 TI - [The characteristics of extracting 2,4-dinitrophenol and 2,4,6-trinitrophenol from aqueous solutions]. PMID- 8009547 TI - [The determination of etatsizin in cadaveric material]. AB - Methods for ethacizine isolation from cadaveric material by acetonitrile acidified with 10% oxalic acid to attain pH 2.0 followed by ether purification have been developed. Extraction photo-colorimetry using methyl orange was used for measurement of ethacizine isolated from cadaveric material. PMID- 8009548 TI - [The determination in cadaveric material of drugs used for the interruption of pregnancy]. AB - A method for detection and measurements in cadaveric material of some drugs used to induce abortions has been developed. The drugs were measured by spectrophotometry, photo-electro-colorimetry, and argentometry. Detection threshold by the said methods was 0.5 to 3 mg%. PMID- 8009549 TI - [Returning to the thirties ...]. PMID- 8009551 TI - [The diagnosis of simulation in forensic psychiatric practice]. AB - The author discusses one of the most important problems in practical forensic psychiatry, simulation of mental disorders. Classification of simulation types is presented, major neuromental disorders enumerated which are simulated by subjects accused of crimes, methods of diagnosis and general regularities typical of all types of simulation behavior are described. PMID- 8009550 TI - [Forensic medical expertise in connection with professional violations of the law by pediatricians]. PMID- 8009552 TI - [Theoretical problems in the methodology of postmortem forensic psychiatric expertise]. AB - Presents expert and methodological analysis of specific features of postmortem forensic psychiatric and complex psychological-psychiatric expert evaluations. Validates approaches to, rules and criteria of expert evaluations of mental status of suicide victims and of victims who told before dying about violations committed in respect of themselves. PMID- 8009553 TI - [Anatolii Fedorovich Koni and forensic medicine (on the 150th anniversary of his birth)]. PMID- 8009554 TI - [One tragedy in the history of Russia (Dmitrii Ivanovich)]. PMID- 8009555 TI - [Defects in the delivery of medical care to the population and their forensic medical evaluation]. AB - A total of 177 records of expert evaluations carried out in 1987-1992 are reviewed, describing 526 cases of defective medical care. The incidence of accusations of medical workers of various specialties is analyzed, as is the incidence of inadequate care at various therapeutic institutions and at different stages of medical care, the outcomes of errors, and structure of errors made at prehospital and hospital stages. PMID- 8009556 TI - [The mechanisms and sequence of the changes in the morphological properties of rib fractures with time]. AB - The authors describe the biotribological process, disclose mechanisms and time course of morphological changes in fractured bones as exemplified by interactions between the ends of fragments in an extension fracture of a rib. These changes result from contacts between fragments due to persistent respiration and parallel processes closely connected, friction and repair regeneration. The data on mechanisms and time course of morphological changes in a fractured bone may prove useful not only for forensic medicine specialists, but for traumatologists as well. PMID- 8009557 TI - Clomipramine therapy in the geriatric hospital: experience with therapeutic drug monitoring. AB - Sixty-nine patients, aged 63-98 years and admitted at the Geneva Geriatric Hospital, were included in the present retrospective study. They received clomipramine orally, 50 or 75 mg/day. Blood concentrations of clomipramine were measured as part of a routine drug monitoring program. Comparison with a reference population of patients aged < or = 65 years indicated that elderly patients with concomitant somatic diseases reach higher dose-normalized concentrations of clomipramine and increased parent drug to demethylated metabolite ratios, as a consequence of impaired demethylation (approximately 50%) and hydroxylation (approximately 25%). Sixty-five percent of patients showed clinical improvement, with a maximum rate of satisfactory response observed in major depression. Severe side effects, such as symptomatic hypotension or confusion, were seen in 20% of patients. Because of 10- and 15-fold interindividual variations in the concentrations of clomipramine and its metabolite, respectively, therapeutic drug monitoring can provide valuable assistance to clinical judgment in individual dose adjustment for patients whose old age, associated somatic diseases, and comedication necessitate additional precautions. PMID- 8009558 TI - Suggestions for the optimization of the initial tobramycin dose in adolescent and adult patients with cystic fibrosis. AB - Clinical pharmacokinetic data of intravenously administered tobramycin in 34 patients with cystic fibrosis (CF) were correlated with patient parameters. Patients began tobramycin therapy with 10 mg/kg/day in three divided doses. Peak and trough serum concentrations were measured. Tobramycin dose was adjusted to a 30 min postdose peak of 10 mg/L and a predose trough of 1 mg/L. Pharmacokinetic data were calculated according to a one-compartment open model and were correlated with clinical data. Tobramycin half-life and total body clearance did not correlate with age, actual body weight, lean body mass, height, or body surface area. Tobramycin volume of distribution correlated with actual body weight (p < 0.02), lean body mass (p < 0.002), height (p < 0.05), and body surface area (p < 0.01), but not with age. The required daily dose after adjustment to a peak serum concentration of 10 mg/L and a trough level of 1 mg/L correlated with lean body mass (p < 0.02) and body surface area (p < 0.05). Based on our findings, the initial daily dose of tobramycin in patients with CF should be calculated by lean body mass rather than actual body weight or body surface area. A formula is presented to calculate the initial daily dose of tobramycin in CF patients who have normal renal function. Monitoring of tobramycin serum levels remains, however, necessary. PMID- 8009559 TI - Improved therapeutic monitoring of drug interactions in epileptic children using carbamazepine polytherapy. AB - Drug interactions in epileptic children with carbamazepine (CBZ) polytherapy were investigated by analysis of total and free CBZ and its metabolites simultaneously. Heteroinduction effects of CBZ metabolism by other antiepileptic drugs (AEDs), including phenytoin (PHT), phenobarbital (PB), or primidone (PRM), were clearly demonstrated. Serum CBZ level/dose ratios in patients taking CBZ plus other AEDs were decreased while CBZ-10,11-epoxide (CBZ-E) and trans-10,11 dihydroxy-10,11-dihydro-CBZ (CBZ-H) concentrations were significantly increased compared to patients with CBZ alone. Concentration ratios of CBZ-H/CBZ and CBZ E/CBZ were also significantly higher in patients taking CBZ plus other AEDs. Interactions between CBZ and valproic acid (VPA) involved both protein binding displacement and metabolic inhibition. Patients taking CBZ plus VPA showed significantly increased free fractions of CBZ and CBZ-E and substantially increased serum CBZ-E concentrations and CBZ-E level/dose ratios, while CBZ-H/CBZ E concentration ratios were decreased compared with patients on CBZ alone. Since this approach investigates the in vivo relationship between substrates and products of the enzymes involved in CBZ biotransformation (the ratios between CBZ and its metabolites), detailed information about the activities of the enzymes may be obtained. This approach appears to be a practical way to improve the monitoring of CBZ metabolism influenced by various physiological or pathological conditions and achieve a better understanding of the drug interactions under different drug regimens (coadministered inhibitor or inducer). This principle may also be adopted for other drugs with similar metabolic characteristics. PMID- 8009560 TI - A rational basis for the measurement of free phenytoin concentration in critically ill trauma patients. AB - Phenytoin binding to serum proteins and factors influencing protein binding were investigated in 38 critically ill trauma patients. In 24% of these patients, the free fraction of phenytoin was < or = 10%, whereas in 76%, the free phenytoin fraction was increased > 10%--up to 24%. Nonantiepileptic comedication, sex, or age had no influence on phenytoin binding in any of the 38 patients. Elevated free phenytoin fraction was found in those with hypoalbuminemia and hepatic and renal impairments. In these patients, the free phenytoin fraction should be measured routinely. PMID- 8009561 TI - Phenytoin age-dose-concentration relationship in children. AB - A list (n = 423) of phenytoin steady-state concentrations from children taking phenytoin alone or in combination with other drugs (n = 308) was obtained from our therapeutic drug monitoring database (1984-1990). Only 43% of concentrations were within the commonly accepted "therapeutic" or "reference" range (10-20 mg/L). Age-dose-concentration relationships showed that while occasional concentrations were above 20 mg/L, many patients receiving commonly recommended pediatric phenytoin doses (4-8 mg/kg/day) achieved concentrations below the reference range, especially children under 3 years of age. Michaelis-Menten pharmacokinetic parameters, maximal elimination rate (Vmax) and Michaelis constant (Km), were evaluated for patients with at least two steady-state concentrations measured for two or more different daily doses. Comedication with other drugs had no effect on either Vmax or Km for phenytoin. Vmax appeared to decrease significantly with age, but there was no age relationship for Km. PMID- 8009562 TI - Utility of pretransplantation cyclosporine pharmacokinetic studies. AB - Pretransplant cyclosporine (CsA) pharmacokinetic analysis of an individual patient is advocated as a more accurate method of determining the optimal dose schedule of CsA for immediate posttransplant patients than traditional mg/kg dosing methods. Eight adult renal transplant candidates (age range 28-69 years) were studied. CsA whole blood analysis was done with a monoclonal fluorescence polarization immunoassay (mFPIA) and high-performance liquid chromatography HPLC. Noncompartmental modeling methods were used to derive CsA pharmacokinetic values. At 1 and 3 months posttransplant CsA pharmacokinetic analyses were completed on five subjects and the average steady state CsA concentration for the dosing interval, Cav, was compared to predicted values calculated from pretransplant pharmacokinetic parameters for each subject. At 6 months posttransplant, actual and predicted Cav were compared in three subjects. Correlation between predicted and actual Cav at 1 month posttransplant was poor (mean actual Cav = 365 ng/ml versus mean predicted Cav = 238 ng/ml; r2 = 0.361). At 3 months posttransplant, the discrepancy between predicted and actual Cav was greater for all five subjects (r2 = 0.039) and this trend persisted for three subjects at 6 months posttransplantation. The mFPIA analysis overestimated the parent CsA concentration when compared to HPLC analysis; the degree of overestimation ranged from 118 to 180%. The mFPIA assay variability may have contributed to the poor correlation between pre- and posttransplant Cav values. There appears to be little or no basis for subjecting transplant candidates to sophisticated pharmacokinetic tests in order to develop specific CsA dosing guidelines for the posttransplant phase. PMID- 8009563 TI - Fluctuation of serum zuclopenthixol concentrations in patients treated with zuclopenthixol decanoate in viscoleo. AB - Zuclopenthixol serum concentrations were measured in 58 psychiatric patients referred for routine therapeutic drug monitoring (TDM). Patients were treated for prolonged time with zuclopenthixol decanoate in viscoleo in doses of 50-500 mg, administered intramuscularly at 14-day intervals. The serum concentration was determined at days 7 (C7) and 14 (C14) following injection. The mean ratio C7/C14 was 2.0 and was independent of the dosage given. In 14 patients, additional blood samples were drawn at day 3 (C3) following injection. The mean ratio C3/C14 of this group was 3.2. An almost log-linear decline of the serum concentration from day 3 to 14 appeared, which corresponds to an apparent half-life of zuclopenthixol in this dosage form of 7.4 days. The marked fluctuations of serum concentrations of zuclopenthixol from peak to trough levels in patients given fortnightly injections of the depot preparation indicate that shorter intervals between injections should be considered in many cases in order to diminish side effects. PMID- 8009564 TI - Evaluation of a Bayesian approach to the pharmacokinetic interpretation of cyclosporin concentrations in renal allograft recipients. AB - The utility of a Bayesian parameter estimation program in the interpretation of cyclosporin concentrations was investigated in a group of 32 patients following renal transplantation. The program was evaluated by comparing concentrations predicted from individual estimates of pharmacokinetic parameters with measured concentrations. A one-compartment model incorporating an exponential, time related change in clearance was used for data collected in the first 4 weeks after transplantation, and predictions of concentrations measured during weeks 5 14 were made using three schemes: a changing clearance model using all data from week 1 onward; a changing clearance model using data from week 4 onward; and a nonchanging clearance model using data from week 4 onward. Results demonstrated that predictions made by the Bayesian program were unreliable during the first 4 weeks of therapy, but that there was a progressive improvement as time after transplantation increased. The changing clearance model was superior to the constant clearance model and its performance was not compromised by including data from the first 4 weeks of therapy. Although the Bayesian approach may help with the interpretation of blood cyclosporin concentrations during maintenance therapy, the large variability in the pharmacokinetics of orally administered cyclosporin limits the usefulness of the approach in the early weeks following transplantation. PMID- 8009565 TI - Prediction of future serum concentrations with Bayesian fitted pharmacokinetic models: results with data collected by nurses versus trained pharmacy residents. AB - Recording the times of dosage administration and serum sampling by trained personnel resulted in significantly greater adherence to the protocol of therapeutic drug monitoring and in significantly greater precision in the achievement of desired serum concentration goals of aminoglycoside therapy than when relatively untrained personnel recorded it as a comparatively unemphasized part of their job. This was true even when only data of peak and trough serum concentrations were used. This study demonstrates that thoughtful data collection by appropriately trained nursing, pharmacy, or other clinical personnel is an essential part of therapeutic drug monitoring and plays a significant role in the optimal individualization of drug dosage regimens for patient care. PMID- 8009566 TI - High-performance liquid chromatography determination of clonazepam in plasma using solid-phase extraction. AB - The use of high-performance liquid chromatography for therapeutic drug monitoring of clonazepam has previously been limited by low sensitivity and labor-intensive liquid-liquid extractions. The present method was developed employing a rapid solid-phase extraction, thus minimising sample workup and providing analytical sensitivity down to 2 micrograms/L using 1 ml of plasma. Plasma samples were loaded onto C18 solid-phase extraction columns, and clonazepam and its internal standard (methyl-clonazepam) were eluted with methanol, dried, and reconstituted in 130 microliters of mobile phase. Chromatographic separation was achieved using a 3-microns RP18 column at 40 degrees C and a mobile phase of 32% acetonitrile and 0.5% glacial acetic acid in distilled water at 0.5 ml/min. Detection was carried out using ultraviolet absorbance at 306 nm. Retention times for clonazepam and methyl-clonazepam were approximately 7 and 12 min respectively. Standard curves were linear over a range of 5-200 micrograms/L with intraassay coefficients of variation of 1.2 and 4.8% at 200 and 5 micrograms/L, respectively. Plasma concentrations measured in patient samples were not statistically different from those obtained using an established gas chromatographic method, and quality control specimens from the Heathcontrol EQA Scheme were consistently within +/- 1.2 SD of the group means. There was no chromatographic interference from other benzodiazepines or other drugs used for the treatment of epilepsy. PMID- 8009567 TI - Radioimmunoassay of colchicine with antisera exhibiting variable cross reactivity. AB - Colchicine-specific antibodies were produced in either goats or rabbits immunized with three different colchicine haptens conjugated to bovine serum albumin (BSA) at different coupling sites on the three rings of colchicine. Antibodies exhibited a variable cross-reactivity for metabolites and structural analogs of colchicine, which were dependent on the site at which colchicine coupled to the protein carrier. Specificity was also checked on urine samples by separating metabolites using high-performance liquid chromatography (HPLC) and radioimmunoassay (RIA) in tandem. The three antisera presented similar high affinity constants for colchicine of the order of 10(10) M-1. A sensitive RIA for plasma colchicine was developed with each antiserum. The limit of detection of the three RIAs was 0.2 ng/ml. The inter- and intraassay coefficients were < 13%. RIA was linear up to 8 ng/ml. This RIA procedure was used to study the pharmacokinetics of a single dose of 1 mg oral colchicine in healthy volunteers and the colchicine concentrations of 27 plasma samples from patients on long-term colchicine treatment. No significant differences in plasma colchicine concentrations using the three assays were observed. This RIA procedure appears suitable for plasma colchicine pharmacokinetics and monitoring investigations. PMID- 8009568 TI - Determination of fostriecin pharmacokinetics in plasma using high-pressure liquid chromatography assay. AB - Fostriecin is an antitumor antibiotic with marked activity against ovarian, breast, and lung cancer cell lines in the human tumor clonogenic assay. The mechanism of cytotoxicity in vivo is unknown; in vitro it has been shown to inhibit macromolecular synthesis, interact with the reduced folate carrier system, and inhibit topoisomerase II. Phase I testing of fostriecin in a daily for 5 days schedule has begun in cancer patients. A high-pressure liquid chromatographic method to measure fostriecin in plasma samples was developed using sulfaquinoxaline as an internal standard and ultraviolet detection (268 nm). The extraction efficiency is 70% and the sensitivity limit is 100 ng/ml. The pharmacokinetics of fostriecin were determined in six rabbits following intravenous injection of 12 mg/m2. The mean distribution space was 4.44 L/m2 and the mean plasma clearance was 302 ml/min/m2. The elimination half-life was 11.95 +/- 8.55 min. All rabbits exhibited a 10-60-fold increase in aspartate aminotransferase (AST) and alanine aminotransferase (ALT) that resolved within 48 h of drug administration. PMID- 8009569 TI - High-performance liquid chromatography determination of pravastatin in plasma. AB - Pravastatin is a 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitor that reduces plasma cholesterol levels. Some analytical methods have been described for determination of pravastatin levels in biological fluids, but these methods are rather cumbersome and involve expensive specialized equipment, usually not available in a clinical setting. A new technique, reversed-phase high-performance liquid chromatography (HPLC) with ultraviolet (UV) detection capability, has been developed for the analytical determination of pravastatin in plasma. Extraction and sample clean-up procedures are simple and rapid to execute, yet yield chromatograms virtually free of interference from endogenous plasma constituents and other antihypercholesterolemic agents or drugs usually taken concomitantly with pravastatin. Our detection limit for pravastatin was 2 ng/ml. Standard curves were linear between 5 and 200 ng/ml, with a coefficient of variation (CV) of < 10% at the limits of quantitation. This method was used to study pravastatin plasma levels in two hypercholesterolemic heart-transplant recipients and two hypercholesterolemic nontransplanted patients. We conclude that the method reported here would be ideal for therapeutic pravastatin monitoring in patients. PMID- 8009570 TI - Quantitation of morphine, morphine-3-glucuronide, and morphine-6-glucuronide in plasma and cerebrospinal fluid using solid-phase extraction and high-performance liquid chromatography with electrochemical detection. AB - An original, sensitive, and specific high-performance liquid chromatographic (HPLC) assay was developed for the quantitation of morphine and its two major metabolites, morphine-3-glucuronide (M3G) and morphine-6-glucuronide (M6G), in human plasma and cerebrospinal fluid (CSF) and in rat plasma, using hydromorphone as the internal standard. Solid-phase extraction was used to separate morphine and its glucuronide metabolites from plasma constituents. Extraction efficiencies of morphine, M3G, and M6G from human plasma samples (0.5 ml) were 84, 87, and 88%, respectively. Extraction efficiencies of morphine, M3G, and M6G did not differ significantly (p > 0.05) between human plasma and CSF or rat plasma. Morphine, M3G, M6G, and hydromorphone were separated on a 10 mu C8 Resolve radially compressed cartridge using a mobile phase comprising methanol:acetonitrile:phosphate buffer, (0.0125M pH 7.5; 10:10:80), in which 11 mg/L of cetyltrimethylammonium bromide (cetrimide) was dissolved. Quantitation was achieved using a single electrochemical detector at ambient temperature (23 degrees C). Standard curves were linear over the ranges 0.020-2.190, 0.027-2.709, and 0.027-0.542 microM for morphine, M3G, and M6G, respectively. Lower limits of detection for morphine, M3G, and M6G in human plasma and CSF samples (0.5 ml) were 0.020, 0.027, and 0.027 microM, respectively. Corresponding lower limits of detection in rat plasma (0.1 ml) were 0.102, 0.135, and 0.135 microM, respectively. Intraassay precision for low and high concentrations of morphine, M3G, and M6G were < 23 and < 8% respectively. Similarly, interassay accuracy for low and medium concentrations of morphine, M3G, and M6G were < 17% and were < 9% for high concentrations. PMID- 8009571 TI - Monitoring of pefloxacin serum concentrations in intensive care unit patients: comparison of a new immunoassay with high-performance liquid chromatography. AB - Serum quinolone concentrations are not routinely measured in clinical practice. However, in order to optimize quinolone treatment, monitoring of serum concentrations could sometimes be useful particularly in critically ill patients. A new enzyme-linked immunosorbent assay (ELISA) that permits direct determination of pefloxacin in serum is described. To validate this new assay, pefloxacin concentrations were measured in 314 serum samples from 74 intensive care unit patients treated with pefloxacin (400 mg i.v. twice daily). Reference concentrations were obtained by reverse phase high-performance liquid chromatography (HPLC) with spectrofluorometric detection. Results showed that concentrations measured by ELISA correlated very well with those by HPLC (r = 0.957; y = 1.03 and x -0.15). In this population, the concentrations found by ELISA varied between individuals (Cmin = 0.70-39 micrograms/ml; Cmax = 5.2-40 micrograms/ml). However, 86% of the measured Cmax and Cmin levels were adequate for optimal pefloxacin therapy. Only 11% of Cmin and 14% of Cmax were below the optimal values (i.e., 2 and 8 micrograms/ml, respectively). These results suggest that despite the large therapeutic index of pefloxacin, monitoring of its serum concentrations using a rapid ELISA technique may be useful for optimal antimicrobial treatment of certain intensive care unit patients. PMID- 8009574 TI - Evaluation of the in vitro stability of digoxin in saliva. PMID- 8009572 TI - Interethnic differences in omeprazole metabolism in the two S-mephenytoin hydroxylation phenotypes studied in Caucasians and Orientals. AB - Two independent studies showed that the 5-hydroxylation, but not the sulfoxidation, of omeprazole is more rapid in extensive metabolizers (EMs) than in poor metabolizers (PMs) of S-mephenytoin. In Caucasian, Chinese, and Korean PMs, the mean oral clearances were similar and not significantly different (85, 73, and 59 ml h-1 kg-1, respectively). However, the geometric mean clearance in Caucasian EMs (950 ml h-1 kg-1) was higher than in both Chinese EMs (426 ml h-1 kg-1, p < 0.05) and Korean EMs (446 ml h-1 kg-1, p < 0.01). The incidence of PMs of S-mephenytoin is higher in Chinese (14.6%) and Koreans (12.6%) than in Swedish Caucasians (3.3%). Therefore, the proportion of heterozygous compared to homozygous EMs is higher in Orientals than in Caucasians. This might explain the higher clearance of omeprazole in Caucasian EMs compared to the clearance of omeprazole in Chinese and Korean EMs of S-mephenytoin. PMID- 8009573 TI - Evaluation of dosage-release formulations on inhibition of drug clearance: effect of sustained- and immediate-release verapamil on propranolol pharmacokinetic parameters. AB - Limited information exists regarding the influence of dosage-release formulation on inhibition of drug metabolism. Therefore, the purpose of this study was to evaluate the effect of immediate-release (IR) and sustained-release (SR) verapamil on the pharmacokinetic parameters of propranolol in 12 healthy men. IR propranolol, 160 mg, was administered alone (Phase A) and following either IR verapamil, 80 mg t.i.d., (Phase B) or SR verapamil, 240 mg q.d., (Phase C) in a randomized crossover fashion. Of the 12 subjects enrolled, only seven were able to be analyzed secondary to assay interference. Oral clearances for L-propranolol for Phases A, B, and C were 198 +/- 70, 156 +/- 76, and 143 +/- 85 L/h, respectively. Oral clearances for D-propranolol for Phases A, B, and C were 203 +/- 96, 172 +/- 96, and 152 +/- 102 L/h, respectively. No significant differences were observed. However, when the verapamil groups (Phase B and C) were combined and compared to Phase A, a significant decrease in clearance for propranolol isomers was observed. In conclusion, due to the unexpected low numbers of patients evaluated, no significant differences in oral clearance were observed among the three treatment phases. However, there is a trend suggesting that SR verapamil had the greatest effect on propranolol clearance, which may warrant caution when changing from one formulation to another. PMID- 8009575 TI - Conscious sedation in a specialty hospital. AB - 1. The patient under i.v. conscious sedation retains the ability to independently maintain a patent airway and respond appropriately to verbal commands and physical stimulation. He or she also has a depressed level of consciousness, and decreased pain and anxiety. 2. For a nurse to administer conscious sedation, conscious sedation policies, procedures and protocols must be in place within the institution. 3. Patients receiving conscious sedation must be monitored for physical changes in blood pressure, cardiac rate and rhythm, oxygen saturation, skin condition, pain, emotional status, and cognitive ability. PMID- 8009576 TI - Effects of sedative music on patient preoperative anxiety. AB - 1. Anticipating surgery frequently produces anxiety. Preoperative surgical patients that are exposed to music experience less anxiety. 2. A patient's music preference can be noted during assessment for use throughout the perioperative experience. 3. The application of music as therapy to reduce fear and anxiety is highly relevant to the work of the perioperative nurse, with regard to a more individualized and holistic approach to patient care. PMID- 8009577 TI - Dr. Cohen's myringotomy day at the Outpatient Care Center. Interview by Nancy L Zinner. AB - 1. Seventy percent of children develop at least one bout of otitis media. Myringotomy is done whenever serous otitis media fails to resolve after medical therapy. 2. The Outpatient Care Center (OCC) at Jewish Hospital in Louisville, the Kentucky Commission for Handicapped Children, and the Indiana Crippled Children's Commission have collaborated to provide cost-effective middle ear ventilation tube surgery for children in the greater Louisville area and southern Indiana. 3. On a typical morning, the OCC's first patient arrives in the operating room at 7:30 AM. The 20th patient is usually out of the operating room by 11:00 AM. Teamwork in all areas allows the cases to flow smoothly. PMID- 8009578 TI - Staff education can prevent OR fires. AB - 1. Every operating room has the elements necessary to start a fire: oxidants (O2, N2O), ignition sources, and fuel. 2. A team approach, including nursing, anesthesia and surgery members, should be used in assessing fire safety in the operating room. 3. Staff knowledge of fire safety can be assessed by written tests. An appropriate fire safety program can be developed based on the test results. 4. Fire evacuation drills and hands-on use of fire extinguishers should be included in any OR fire safety program. PMID- 8009579 TI - Carpal tunnel release: scoping out the carpal tunnel. AB - 1. Conservative treatments for carpal tunnel syndrome (CTS)--such as rest, splinting of the wrist, use of anti-inflammatory drugs, and steroid injections- are used when symptoms are manageable and short term. 2. If CTS symptoms worsen- or there is evidence of neurosensory deterioration or thenar muscle wasting--then surgery becomes the only recourse. 3. Endoscopic release of the carpal tunnel results in less surgical trauma to the patient than the open method of release, resulting in less postoperative pain and scarring, and faster recovery time, resolution of paresthesia and pillar pain, improvement of grip and pinching strength, and return to work and activities of daily living. PMID- 8009580 TI - The importance of nursing principles. PMID- 8009581 TI - Stress can kill. PMID- 8009582 TI - Evaluation and management of early HIV infection. PMID- 8009583 TI - Coping with difficult changes. PMID- 8009584 TI - Living through litigation. PMID- 8009585 TI - Laparoscopic fundoplication: an alternate approach in the surgical treatment of esophageal reflux (continuing education credit). AB - 1. Laparoscopic fundoplication is more "patient friendly" than the comparable open procedure, affording shorter postoperative recovery and faster return of the patient to normal activity. 2. Laparoscopic fundoplication achieves the same results and is essentially the same procedure as open fundoplication, but with smaller incisions and less pain. 3. The procedure takes time to learn, but once mastered, it cuts the OR time to approximately the same as for the open fundoplication. PMID- 8009587 TI - Synergistic immunosuppressive actions of cyclosporine with a mouse anti-rat alpha/beta-T cell receptor monoclonal antibody. AB - A mouse IgG1 mAb (R73) directed against the rat alpha/beta-TCR was documented not only to prolong the survival of allografts across major RT1 plus non-RT1 antigenic disparities, but also to display a synergistic immunosuppressive interaction with CsA. Heterotopic cardiac transplants from Buffalo (RT1b) rats survived significantly longer in Wistar-Furth (RT1u) hosts treated immediately after the operation with 0.25 mg/kg R73 i.v., with a mean survival time of 11.0 +/- 5.5 versus 6.8 +/- 1.2 days in the untreated group (P < 0.01). Administration of 0.5 or 5.0 mg/kg R73 displayed dose-dependent prolongation of survival to 17.0 +/- 8.3 days (P < 0.05) or 28.6 +/- 14.0 days (P < 0.01), respectively. One 0.5 mg/kg i.v. dose of R73 delivered to normal Wistar-Furth hosts produced peripheral T cell depletion that reversed after 16 days. Three injections of 0.5 mg/kg R73 on days 0, 2, and 4 prolonged allograft survival to 52.5 +/- 38.6 days compared with 17.0 +/- 8.3 days with a single dose (P < 0.01). Addition of 3 daily doses of 5 or 10 mg/kg CsA administered per oral gavage to a single dose of 0.05, 0.25, or 0.5 mg/kg R73 injected on day 0 produced a synergistic effect to prolong allograft survival, as determined by the rigorous median-effect analysis. The synergistic interaction, which may be explained by the inhibitory effect of CsA on Ca(2+)-dependent pathways triggered after activation of TCR, the target of R73, warrants clinical investigation in order to assess the potential impact of anti-alpha/beta-TCR mAb on CsA-based immunosuppressive regimens. PMID- 8009586 TI - A non-activating "humanized" anti-CD3 monoclonal antibody retains immunosuppressive properties in vivo. AB - OKT3, a mouse anti-human CD3 mAb, is a potent immunosuppressive agent used in clinical transplantation to prevent or treat allograft rejection. Associated with this therapy is the systemic release of several cytokines that result in a series of adverse side effects. This release of cytokines is dependent on the cross linking mediated by OKT3 between T cells and the Fc gamma R-bearing cells. To generate an anti-human CD3 mAb with reduced activating properties as compared with OKT3, we have transferred the complementary determining regions of OKT3 onto human IgG frameworks and then performed point mutations that reduce the affinity of the "humanized" anti-CD3 mAbs for Fc gamma Rs. Initial, in vitro, studies showed that whereas OKT3 and the parental humanized anti-CD3 mAbs activated T cells similarly, a humanized Fc variant failed to do so. Both the Fc variant and the activating anti-CD3 mAbs induced comparable modulation of the TCR and suppression of cytolytic T cell activity, in vitro. In the current study, we exploited an experimental model in which human splenocytes from cadaveric organ donors were inoculated into severe combined immunodeficient mice (hu-SPL-SCID mice) to test the activating and immunosuppressive properties of these anti-human CD3 mAbs in vivo. Unlike injection of OKT3 or of the parental humanized mAb, administration of the Fc variant did not result in T cell activation in vivo, as evidenced by the lack of induction of surface markers of activation, and of systemic human cytokines, including IL-2. Importantly, similar prolongation of human allograft survival was achieved with all anti-CD3 mAbs, indicating that the nonactivating anti-CD3 mAbs retained significant immunosuppressive properties in vivo. Thus, the use of an Fc variant in clinical transplantation should result in fewer side effects than observed with OKT3, while maintaining its clinical efficacy. PMID- 8009589 TI - Beneficial effects of cyclosporine on reoxygenation injury in hypoxic rat liver. AB - The effect of CsA on hypoxia-reoxygenation injury was studied in perfused rat livers. CsA did not attenuate hypoxic injury, as assessed by the release of lactate dehydrogenase and mitochondrial aspartate aminotransferase. During reoxygenation, the release of lactate dehydrogenase was also not affected by CsA. However, the release of mitochondrial aspartate aminotransferase into the cytosol, which indicates mitochondrial injury, was significantly reduced by CsA. The effect of CsA on mitochondrial function during hypoxia-reoxygenation was also investigated. CsA administration increased both the respiratory control ratio and the adenine nucleotide content after reoxygenation in both isolated mitochondria and perfused livers. In addition, glucose production by perfused livers after reoxygenation was increased by CsA. We conclude that the beneficial effect of CsA on hypoxia-reoxygenation injury may be partly due to protection of the mitochondria against reoxygenation injury. PMID- 8009588 TI - Human peripheral blood lymphocyte reconstituted severe combined immunodeficient (hu-PBL-SCID) mice. A model for human islet allograft rejection. AB - Severe combined immunodeficient (SCID) mice have become a promising tool for the development of models of human immunologic process. We report the development of a reproducible technique for engrafting SCID mice with human PBL (hu-PBL-SCID). Our results show that a booster injection of anti-CD3 antibody stimulated human lymphocytes given 2 days after the initial injection of lymphocytes will improve the efficiency of chimera establishment to 86.7% (13 out of 15). There was also good correlation among detection of human Ig, human CD3+ cells, and human DNA by polymerase chain reaction amplification in the circulation of hu-PBL-SCID mice. Questions remain concerning the immune function of the human lymphoid cells in the SCID mouse. In this study, we analyzed the ability of human T cells in SCID mice to reject human islet allografts transplanted under the kidney capsule. Human islet allograft function assessed by human C-peptide levels demonstrated failure of islet allografts within 21 days after transplantation in hu-PBL-SCID. In contrast, human islets grafted in unreconstituted SCID mice continued to function for greater than 60 days. Recovered human T cells from rejected islets of hu-PBL-SCID mice displayed specific cytolytic activity against HLA class I matched islets, while the recovered cells from spleen of hu-PBL-SCID mice showed minimal specific cytotoxicity against islets. These results suggest that graft infiltrating lymphocytes were activated by the engrafted islets within the hu-PBL SCID, causing the eventual rejection of the human islet allograft. Thus, engraftment of the anti-CD3 antibody-primed human PBL results in a mouse-human chimera with a functionally competent human immune system that is capable of rejecting a human islet allograft. PMID- 8009590 TI - 31P nuclear magnetic resonance spectroscopic evaluation of liver preservation solutions. AB - The individual effects of verapamil and 2 antioxidants on perfused rat liver nucleoside triphosphate (NTP) recovery following cold storage in University of Wisconsin (UW) solution was assessed using 31P nuclear magnetic resonance spectroscopy. The pharmacological agents were added to UW solution and were present only during organ storage. NTP recovery was significantly higher for the 24-hr UW + 40 microM verapamil group as compared with the 24-hr UW group. None of the other pharmacological agents caused a significant increase in NTP recovery. These findings suggest that addition of verapamil to UW organ preservation solution may result in better poststorage liver function. PMID- 8009591 TI - Clinical evaluation of induction immunosuppression with a murine IgG2b monoclonal antibody (BMA 031) directed toward the human alpha/beta-T cell receptor. AB - Mouse mAbs directed against the alpha/beta-TCR were tested in clinical phase II and in triple-blind, randomized phase III studies. A clinical phase II trial administered 50 mg of murine anti-human alpha/beta-TCR mAb (BMA 031) intravenously on the day of, as well as 2 and 4 days after, cadaveric donor renal transplantation in combination with a CsA/prednisone regimen. None of 12 patients showed even moderately adverse side effects. A phase III, triple-blind randomized trial enrolled 24 patients in the BMA 031 group and 22 patients in a placebo control group. BMA 031 treatment significantly reduced the incidence of rejection events within the first 10 posttransplant days to 1 patient versus 9 episodes in the placebo group (P < 0.01). By the end of 30 days, 6 rejection episodes had occurred in the BMA 031 group and 11 in the control cohort (P = NS). After a minimum of 30 months follow-up, the actual allograft survival rate was 87% in the BMA-treated group compared with 68% in the control cohort. PMID- 8009592 TI - Should liver transplantation be performed for patients with hepatitis B? AB - Because of the almost universal recurrence of hepatitis B surface antigenemia (HBsAg) after liver transplantation, some centers have questioned whether these patients are appropriate allograft candidates. Since January 1984, 51 patients with hepatitis B (HBV) underwent OLT at our center. No therapy was given to prevent reinfection. Three patients underwent retransplantation. The indications for transplant included fulminant HBV (13 patients), chronic HBV (33 patients), and hepatocellular carcinoma (HCCA) in addition to HBV (5 patients). Incidental HCCA was found in 2 of the 33 patients thought to have only chronic HBV. Actuarial survival for the entire group was 57% at 1 year and 54% at 3 years. Of the 23 patients who died, only 4 deaths were attributable to recurrent HBV liver disease. Four patients survived less than 4 days due to primary graft nonfunction. Ten patients died in the first 3 months from sepsis. Although all patients who died beyond 30 days had recurrent HBsAg, only 4 deaths were attributable to recurrent HBV. The remaining 5 deaths were caused by portal vein thrombosis, bile leak, lymphoma, pancreatitis, and sepsis occurring at 15 months. Excluding the 4 patients who died from primary graft nonfunction, actuarial survival was 63% at 1 year and 60% at 3 years. Of the 28 survivors, 24 are HBsAg positive; however, only 5 have recurrent HBV liver disease. Multiple factors were evaluated to determine their influence on survival; i.e., HBV serology, United Network for Organ Sharing status, fulminant versus chronic HBV, incidence of rejection, immunosuppression, transfusion requirements, and presence of HCCA. Of these, only the presence of HCCA adversely affected outcome. Of the 7 patients with HCCA and HBV, 6 patients died within the first 6 months and 1 patient has recurrent HBV liver disease at 25 months. Actuarial survival excluding those patients with HCCA was 64% at 1 year and 61% at 3 years. Based on our results, patients with HBV and associated HCCA have a poorer prognosis and should probably be excluded from transplantation. Although the survival for patients with HBV undergoing liver transplantation is inferior to that expected in patients with some other diagnoses, long-term survival can be achieved in a majority of these patients despite recurrence of HBsAg. We believe that appropriately selected patients with a diagnosis of HBV alone should continue to be candidates for liver allografts. PMID- 8009593 TI - Complement system activation during orthotopic liver transplantation in man. Indications of peroperative complement system activation in the gut. AB - Sixteen patients with acute and chronic liver disease undergoing OLT were studied regarding the role of the liver and the gut in complement activation. Also, the relation between complement activation and clinical manifestations during the liver transplantation reperfusion period was investigated. Blood samples for measurement of complement anaphylatoxin C3a (C3a), complement anaphylatoxin C5a (C5a), and terminal C5b-9 complement complex (TCC) were taken simultaneously from the central venous catheter and the radial arterial line before starting the operative procedure, 1 min before declamping, and 1-2 min, 5 min, 30 min and 6-12 hr after declamping. Simultaneous blood sampling from the radial arterial line, central venous catheter, portal vein, and hepatic vein was performed 1-2 min and 5 min after completed unclamping. Elevated plasma levels of C3a and TCC were found upon reperfusion, while C5a levels remained unchanged throughout the operation compared with the preoperative levels. The levels of C3a in the portal vein were higher compared with the levels in the simultaneously obtained samples from the radial artery. The results indicate complement cascade activation located to the gut during the reperfusion phase of OLT. Seventy-five percent of the patient studied suffered from the postreperfusion syndrome, indicated by profound hypotension upon reperfusion of the transplanted liver. There was a significant correlation between high concentration of C3a anaphylatoxin and development of profound hypotension. PMID- 8009594 TI - Recipient risk factors have an impact on technical failure and patient and graft survival rates in bladder-drained pancreas transplants. AB - Recipient selection criteria for pancreas (Px) transplantation differ among centers, based on perceived recipient risk factors, and their validity has not been determined. At the University of Minnesota we have been very liberal in accepting patients for Tx, some of whom have risk factors cited as exclusion criteria by other centers, giving us the opportunity to determine, retrospectively, the impact of their presence on outcome. Between July 1986 and March 1993, we performed 319 bladder-drained cadaver Px Txs at the University of Minnesota, 166 simultaneous with a kidney (SPK), 68 after a kidney (PAK), and 85 alone (PTA). To determine which putative "risk factors" influence patient and graft survival, we used uni- and multivariate (Cox regression) analyses to assess the impact of recipient category, duration of diabetes, and age at onset and at Tx; presence of pre-Tx cardiac (CD) disease (myocardial infarction, bypass, angioplasty), peripheral vascular disease (PVD) (stroke, bypass, angioplasty, amputation); blindness, hypertension, and excess weight; and of Px re-Txs. The incidences of all risk factors except re-Tx were significantly higher in SPK than PTA recipients. Px re-Txs comprised 40% of PAK, 26% of PTA, and 10% of SPK cases (P < 0.0001). Duration of diabetes correlated (P < or = 0.01) with all risk factors but one (hypertension). Recipient age correlated (P < or = 0.01) with CD, blindness, duration of diabetes, and age at onset of diabetes; CD risk factors correlated (P < 0.015) with hypertension and PVD. Recipient age (> or = 45) influenced the technical failure rate only in SPK recipients, with a relative risk (RR) of 2.13 (P = 0.08). Recipient age influenced Px graft and patient survival rates in both SPK and PAK recipients; for those > or = 45, the RR of graft loss was 1.73 and 1.76, respectively (P < or = 0.25), and the RR for ultimately dying was 3.07 in PAK (P = 0.02) and 5.86 in SPK (P = 0.17) recipients. SPK recipients with CD factors were at higher risk to ultimately die (RR = 3.78, P = 0.009), independent of age. Px re-Txs were not at higher risk to fail in PTA, but were in PAK recipients (RR = 1.86, P = 0.09); the risk for technical failure was higher for re-Txs only in SPK recipients (RR = 2.11, P = 0.24). Blindness, hypertension, PVD, and duration of diabetes did not negatively influence patient and graft outcome in any recipient category.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8009595 TI - Cyclosporine challenge in the decision of combined kidney-pancreas versus solitary pancreas transplantation. AB - Combined kidney-pancreas transplantation has become the treatment of choice for many patients with end-stage diabetic nephropathy. Pancreas transplantation (PTx) alone is an option for type I diabetic patients without end-stage diabetic nephropathy. Knowledge of factors contributing to or predicting the rate of renal deterioration (including the effect of CsA on the patient's renal function before transplantation) is necessary to determine candidacy for either kidney-pancreas transplantation or PTx alone. To address this issue, we selected 12 pre-uremic patients with creatinine clearances (CrCl) above 40 ml/min and less than 100 ml/min to participate in a 6-week oral CsA challenge test. Serum chemistries, including serum creatinine (SCr) and CsA level, were measured weekly. Urinary protein and CrCl were measured at 0, 2, 4, and 6 weeks. Glomerular filtration rate (GFR) (by 125I-sodium iothalamate clearance) was measured at 0, 3, and 6 weeks. All patients initially received oral CsA at 10 mg/kg/day in 2 divided doses. Doses were adjusted to maintain a 12-hr trough level of 500-1000 ng/ml using a whole blood polyclonal TDX assay. Data are presented as mean +/- SEM and as box-plot graphs. One patient was a CsA challenge test failure because SCr exceeded 3.0 mg/dl despite a reduction in CsA dose and level. Therefore, this patient was not a candidate for PTx alone and was excluded from further analysis. Among the 11 nonfailures, the mean CsA level at 6 weeks was 640 +/- 76 ng/ml. SCr increased from 1.2 +/- 0.1 mg/dl to 1.6 +/- 0.1 mg/dl (33% increase) (P = 0.0001). CrCl decreased from 82 +/- 9 ml/min to 63 +/- 8 ml/min (24% decrease) (P = 0.03). GFR decreased from 95 +/- 15 ml/min to 70 +/- 10 ml/min (26% decrease) (P = 0.009). CrCl and GFR did not differ from one another at 0 and 6 weeks (r = 0.77 and 0.98; P = 0.3 and 0.7, respectively). Urinary protein decreased from 1.0 +/- 0.3 g/day to 0.7 +/- 0.3 g/day at both 4 and 6 weeks (P = 0.03 and 0.06, respectively). Three of the 11 patients have not yet received transplants. Eight patients subsequently received PTx alone and were followed prospectively. Two allografts were lost early to rejection. Six were followed from 5 to 19 months after PTx alone. Serum creatinine and CrCL measurements during the CsA challenge test predicted post-PTx levels: SCr 1.6 +/- 0.1 vs. 1.7 +/- 0.3 mg/dl, P = 0.48, and CrCl 68 +/- 10 vs. 53 +/- 3 ml/min, P = 0.17, respectively. PMID- 8009596 TI - Epstein-Barr virus-specific cytotoxic T cell response in cardiac transplant recipients. AB - PBLs from 10 normal seropositive donors, 15 precardiac transplant patients, and 17 postcardiac transplant patients have been assayed for their ability to mount a cytotoxic T cell response to both A- and B-type EBV. Compared with the results obtained with healthy seropositive donors, pre- and posttransplant patients had significantly weaker T cell responses against both A-type and B-type EBV. Analysis of individual patients showed a preferential T cell response to B-type EBV in 4/15 pre- and 6/17 posttransplant patients and a preferential T cell response to A-type EBV in 1/15 pretransplant and 2/17 posttransplant recipients. PBMCs were obtained from patients and analyzed for the presence of A- and B-type EBV using polymerase chain reaction. EBV types detected in the PBMCs of each individual were correlated with their EBV-specific CTL response. The results obtained indicated that the EBV-specific cytotoxic T cell response of these patients matched the EBV types with which they were infected. PMID- 8009597 TI - Severe B cell depletion in newborns from renal transplant mothers taking immunosuppressive agents. AB - There have been several reports of successful pregnancies of kidney transplant mothers receiving immunosuppressive agents such as CsA and/or AZA. However, few papers have investigated immune function of neonates from those mothers. We investigated the lymphocyte subpopulations and T cell subsets in cord blood of newborn infants from those mothers. The subjects were 6 infants born to mothers following renal transplantation, who all were receiving CsA, AZA, and methylprednisolone. Cord blood and peripheral blood at 1 month and 3 months of age were obtained from the subjects. Control samples were obtained from 5 normal newborns. The polyclonal antibody used to investigate B cells was anti-F(ab')2 fragment of human immunoglobulin. Direct immunofluorescence staining and flow cytometry were used for the investigation. The number of B cells and the percentage of B cell in total mononuclear cells were significantly lower in the subjects than in normal controls. There was no significant difference between numbers of CD2+, CD4+, or CD8+ cells in the subjects and the controls. This severe B cell depletion remained low at 1 month and 3 months of life in many cases. From our result, it is very possible that the B cell line is more sensitive to immunosuppressants in utero than the T cell line. Infants of mothers taking immunosuppressive agents during their pregnancy should be followed carefully for possible insufficiency of immune function. PMID- 8009598 TI - Cytokine interactions in human mixed lymphocyte culture. AB - Human PBMC of healthy blood donors were used to investigate the interaction of cytokines in human MLC. Two-way MLC was performed because irradiation did not influence the cytokine release. We found different kinetic patterns for IL-2, IFN gamma, and sIL-2R. Production of IFN-gamma was dependent on IL-2 release because anti-IL-2 addition resulted in more than 90% reduced IFN-gamma levels. Treatment with rIL-2 altered IFN-gamma kinetics, but not the total amount of IFN-gamma. Addition of anti-IFN-gamma led to decreased production of IL-2 and sIL-2R. A down regulation of IL-2 and sIL-2R could also be observed after treatment with rIFN gamma. No production of IL-4 and IL-10 was detected in MLC (detection limit 5 pg/ml). This could not be explained by IFN-gamma antagonism because IL-4 and IL 10 were not detectable even after addition of anti-IFN-gamma. Testing the TH1-TH2 cell antagonism, the addition of rIL-4 and rIL-10 resulted in IFN-gamma suppression depending on the timing of exposition. Treatment with rIL-10 inhibited IL-2 and sIL-2R release. We found no production of IL-1 alpha and IL-1 beta in MLC, whereas IL-6 and TNF-alpha release could be detected. Surprisingly, release of IL-6 and TNF-alpha could be blocked completely by addition of anti-IFN gamma. This suggests that the release of IL-6 and TNF-alpha in MLC is dependent on IFN-gamma produced by T cells. In summary, TH1 cytokines play a central role in MLC regulation, whereas TH2 cytokines appear to be of little importance. PMID- 8009599 TI - Lymphoid organ production of immunomodulatory eicosanoids in mice resistant to neonatal tolerance induction. AB - Neonatally induced tolerance of class I and class II alloantigens is difficult to achieve in certain I-E non-expressing hosts that received semiallogeneic cells at birth from strains of mice that express I-E molecules. Although clonal deletion occurs ubiquitously after infusion of the tolerogen-bearing inoculum, the majority of these mice ultimately regain the capacity to reject donor-specific skin graft challenges in adulthood and this is associated with a reacquisition of I-E recognizing and alloreactive T cells as well as a loss of donor chimeric cells. In this study, we determined whether production levels of the eicosanoids prostaglandin E2 (PGE2) and thromboxane B2 (TxB2), both potent modifiers of lymphocyte function, were altered in lymphoid organs concomitant with a breakdown of tolerance in these mice. The levels of TxB2 and PGE2 produced by lymphoid organs were measured in the early/late post-partum periods and immediately before and after skin grafting in B10.S mice (H-2s/I-E-) that had been injected at birth with (B10.S x B10.A)F1 (H-2k/d, I-E+) lymphohematopoietic cells. Phenotypic (e.g., %V beta 11+ T cells) and functional parameters of host donor-reactive effector cell populations along with chimerism were determined simultaneously. We found that TxB2 and PGE2 production fluctuated in the early postnatal periods in naive mice and that the neonatally injected counterparts showed a significant alteration from this pattern, particularly with PGE2. As adults, injected hosts maintained an altered pattern of eicosanoid metabolism and this was accentuated after the rejection or acceptance of a donor-specific skin allograft. Specific patterns emerged after transplant challenge such that neonatally injected mice deleted of V beta 11+ T cells before grafting differed in their eicosanoid secretory profiles; moreover, injected mice that accepted (i.e., tolerant) the donor-specific allograft had a markedly different TxB2 and PGE2 profile than injected/rejecting hosts. In naive mice, the application of 2 subsequent grafts elicited a release of splenic TxB2 and PGE2 that mimicked the pattern seen in the neonatally injected hosts after 1 graft--these latter results give preliminary indication that the generation of memory T cells and the re-exposure to specific alloantigen coincides with a derangement in eicosanoid metabolism.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8009600 TI - Analysis of rejection mechanism in the rat to mouse cardiac xenotransplantation. Role and characteristics of anti-endothelial cell antibodies. AB - Recent reports have demonstrated that humoral factors, especially antibodies elicited by xenoantigens, play an important role in the rejection of concordant cardiac xenografts. These induced antibodies, however, have not been well characterized. Therefore, we investigated the rejection mechanism, especially the role of humoral immunological responses in the concordant rat to mouse cardiac xenograft model. Lewis rat hearts transplanted into C3H/HeN mice were rejected in 5-6 days. The essential role of humoral factors in the rejection was demonstrated by histological analysis of the rejected hearts showing interstitial hemorrhage, scant cellular infiltration, and the dense deposition of mouse IgG, IgM, and C3 on the graft endothelial cells. In addition, mice that received hyperimmune serum (serum at the 10th day after transplantation) rejected rat hearts hyperacutely. Flow cytometrical analysis using cultured donor rat coronary endothelial cells demonstrated the xenoreactive antibodies of all subclasses, but especially strong reactivity of IgM and IgG2a in the serum at rejection. These xenoreactive antibodies were produced against not only MHC, but also non-MHC antigens on graft endothelial cells. In vivo depletion of L3T4+ T cells led to the suppression of xenoreactive antibody production and the prolongation of graft survival, indicating that antibody production in this model needs L3T4+ T cell help. PMID- 8009601 TI - Short-term renal hemodynamic changes in patients receiving a renal allograft. PMID- 8009602 TI - Aspergillus brain abscess after liver transplantation with long-term survival. A case report. PMID- 8009603 TI - Emergency liver retransplantation using a polycystic donor liver. PMID- 8009604 TI - New technique using near-infrared spectroscopy for quantifying nitric oxide during acute rejection of liver allograft. PMID- 8009605 TI - Visceral leishmaniasis: a cause of opportunistic infection in renal transplant patients in endemic areas. PMID- 8009606 TI - Donor-transmitted tumors in lung allograft recipients: report on two cases. PMID- 8009607 TI - Detection of cytomegalovirus-infected cells in bone marrow biopsy specimens obtained before allogeneic bone marrow transplantation from donors and recipients. PMID- 8009608 TI - A double-blind randomized controlled trial of primary isoniazid prophylaxis in dialysis and transplant patients. PMID- 8009609 TI - A comparative study of two-layer cold storage with perfluorochemical alone and University of Wisconsin solution for rat pancreas preservation. PMID- 8009610 TI - Nontherapeutic cyclosporine levels. Sustained-release diltiazem products are not the same. PMID- 8009611 TI - Lyme disease in a kidney transplant recipient. PMID- 8009612 TI - Basic medical equipment: a proposed list. PMID- 8009614 TI - The quantitative buffy coat for the diagnosis of trypanosomes. AB - The use of quantitative buffy coat (QBC) tubes developed for malaria diagnosis is described in the diagnosis of African trypanosomiasis. One hundred and thirty four patients with Trypanosoma gambiense were examined using QBC plus either haematocrit (HCT) or mini anion exchange centrifugation (MAEC) or both. QBC was the only method that detected all 134 patients. QBC proved to be the most sensitive diagnostic test for the detection of trypanosomes in blood. It is simple to use, gives fast results and would be a useful test at the district hospital level. PMID- 8009613 TI - Copper sulphate poisoning. AB - A number of cases of copper sulphate poisoning from the southern region of Bangladesh are presented. There was a high mortality (24.9%) in comparison to other forms of poisoning. Hepatotoxicity, acute renal failure and gastrointestinal bleeding were the main complications. This degree of copper sulphate poisoning in one particular area is cause for alarm. PMID- 8009615 TI - The 'kangaroo-method' for treating low birth weight babies in a developing country. AB - The results of introducing the 'kangaroo method' (constant nursing of the baby skin to skin on the mother's chest), as the exclusive means of treating low birth weight (LBW) babies is reported, in the context of a mission hospital in a developing country without incubators and standard equipment for care of LBW neonates. Details of the method developed are described. The survival of babies born under 1500 g improved from 10% to 50%, whereas that of babies 1500-1999 g improved from 70% to 90%. The method is well accepted by the community, and easily grasped by all hospital staff. Staff expectations concerning survival have dramatically improved, and a considerable saving in workload is experienced. The kangaroo method as described is strongly recommended to all units in developing countries treating LBW babies without modern equipment. PMID- 8009616 TI - Cotrimoxazol in the treatment of Mycobacterium ulcerans infection (Buruli ulcer) in west Africa. PMID- 8009618 TI - Evaluation of vitamin A deficiency in the Yelimane Circle of Mali, west Africa. AB - Of 207 children (aged 4-7 years) in western Mali examined clinically and by conjunctival impression cytology (CIC), 2% had night blindness, no child had Bitot spots and 78% were found to have abnormal CIC suggesting deficiency in vitamin A. In a cohort of 53 children examined by CIC pre- and post-harvest (June and December), abnormal CIC were seen in 77.4% and 54.7%, respectively (P = 0.04). Subclinical vitamin A deficiency is a problem in this area. A seasonal variation is demonstrated. CIC is a useful method for identifying communities with subclinical vitamin A deficiency. A variety of strategies for dealing with vitamin A deficiency are discussed. PMID- 8009617 TI - The health consequences of intrauterine growth retardation in southwestern Ethiopia. AB - Although over 90% of low birth weight deliveries occur in the developing world, knowledge of its occurrence and consequences are largely based on studies in developed populations. The aim of this investigation was to determine the health consequences of intrauterine growth retardation (IUGR) among an historical cohort of children delivered in a regional hospital located in southwestern Ethiopia. Following a census of all births over a three year period 116 full-term, IUGR and normal birth weight (NBW) matched pairs between 3 and 40 months of age were identified. IUGR children were found to be at elevated risk for moderate to severe malnutrition [relative risk (RR) = 2.26 (1.15,4.43)], frequent illnesses (RR = 1.29 (1.13, 1.46)), and current illness (RR 1.52 (1.10, 2.09)). Catch-up growth among IUGR children did not occur. A steady decline in the growth of NBW children resulted in similar anthropometric outcomes by 2 years of age between the two groups. PMID- 8009620 TI - Brown-Sequard syndrome following diphtheria and tetanus vaccines. PMID- 8009619 TI - Myositis ossificans progressiva: from Nigeria. PMID- 8009621 TI - Neuromyelitis optica (Devic's disease) following chicken pox. PMID- 8009622 TI - Ghana. Selective versus comprehensive primary health care. PMID- 8009623 TI - Ladakh. Is tetanus rare at high altitudes? PMID- 8009624 TI - Rapid rural appraisal. PMID- 8009625 TI - Sexual abuse of children in rural Zimbabwe: a report from Elim Hospital. PMID- 8009626 TI - Haematoma testes due to traditional massage in a neonate. PMID- 8009627 TI - Dental caries in children with congenital heart disease. PMID- 8009628 TI - Sputum smear negative pulmonary tuberculosis. PMID- 8009629 TI - Bacteraemia in Blantyre. PMID- 8009630 TI - Animal injuries presenting to Riyadh Armed Forces Hospital: a survey. PMID- 8009631 TI - Epidemiology of cutaneous leishmaniasis in Nigeria: a preliminary communication. PMID- 8009632 TI - Prescription audit for antibiotics in a district hospital. PMID- 8009633 TI - Open access endoscopy: diagnostic role in upper gastrointestinal disorders. PMID- 8009634 TI - Prevalence of paediatric skin diseases in rural Honduras. PMID- 8009635 TI - Does ascariasis, trichuriasis and hookworm infection predispose to non-specific abdominal symptoms among adults in endemic areas? PMID- 8009636 TI - Obstetric uterine ruptures in a rural area in Zaire. AB - Uterine ruptures with their deplorable sequelae constitute a major obstetrical problem in the rural areas of Africa. The maternal and perinatal mortality remain high as a result, mainly due to the lack of early and adequate care for these patients. Grande-multiparity is one of the major predisposing factors. Prevention must necessarily include the availability of family planning advice, improved organization of and access to maternal care, and good supervision during delivery and the post-partum period. The general improvement of the overall socio-economic condition is a pre-condition to the improvement of access to care. PMID- 8009638 TI - [The measurement of cell concentration and size using the AOD-101 cytometer]. AB - A particle sizing counter, elaborated by the Institute of Cytology and Scientific Industry Union "Analytpribor", was evaluated for its effectiveness in analysing different cell suspensions. The mean error of cell concentration measurement is about 3% within the 1-15 x 10(4) ml-1 interval. Cells can be found in suspension at a concentration of 2 x 10(2) ml-1. Cell size can be measured reproducibly within 10% for the interval 3-150 microns. The absolute value of cell size can be obtained after the device graduation with independently sized cells. Such a graduation differs by 5-10% from the graduation with latexes. PMID- 8009637 TI - [The dependence of the quantity of silver granules detectable in interphase nuclei after the silver nitrate staining of the chromosomal nucleolus-organizer regions on the conditions for the hypotonic treatment of the cells and the effect on this index of cell treatment by a pharmacological agent causing dissociation of the nucleolar components]. AB - We investigated effects of hypotonic treatment of cultured HL-60 cells and human fibroblasts, and of DRB on the quantity of AgNORs revealed following AgNO3 staining. The average number of grains increases after KCl hypotonic treatment. The lower the concentration of KCl in the solution, the higher the number of silver grains revealed in the nucleoli due to their dissociation into substructures. The use of adenosine analogue (DRB) before the hypotonic treatment of cells facilitates the following count of silver deposits. A maximum increase in the mean number of silver grains was observed after a 1.5 h incubation. PMID- 8009639 TI - [Arachidonic acid and its products: the pathways of its formation and metabolism in cells]. PMID- 8009640 TI - [Transglial channels in the sympathetic ganglion of Rana temporaria]. AB - Channel across thin layers of glial cells in the frog sympathetic ganglia are demonstrated by means of transmissive electron microscope. The channels have a diameter of 60-130 nm, provided with a structure at their openings and considered to be formed by plasmalemmal vesicles. In the thinnest layers it may be a single vesicle whose membrane fused simultaneously with plasmalemma of the opposite surfaces of layers; in the wider layers channels are formed by a chain of two or more vesicles fused with each other and plasmalemma. The transglial channels are demonstrated also in ganglia fixed during long lasting high frequency preganglionic stimulation (40 Hz, 20 min) and in high K+ concentration in bathing solution (8, 16 and 55 mM). Possible involvement of transglial channels and other forms of fluid phase endocytosis in glial cells in removing a surplus of K+ from nerve cells during their activity is discussed. PMID- 8009641 TI - [The receptor-mediated endocytosis of complexes of colloidal gold with high density lipoproteins by the sinusoidal cells of the isolated rat liver]. AB - Rat hepatic sinusoidal cells absorption of native high-density lipoproteins was studied by electron microscope. Visualization of the endocytosis process was achieved by binding of lipoprotein particles and colloidal gold. The study was carried out on isolated liver perfusing by oxygenated nutritional media which consist of colloidal gold-lipoproteins conjugates. Electron microscope analysis testifies that high-density lipoproteins are absorbed by hepatic sinusoidal cells by means of receptor endocytosis. Both Kupffer cells and endothelial cells have such receptors. Lipoproteins of this class reach hepatic cells in Disse's space through the endothelium, i.e. transcellularly unlike low-density lipoproteins which penetrate paracellularly--through the fenestrae and intracellular contact's ares. PMID- 8009642 TI - [A comparative study of the effect of allopurinol and caffeine on mitotic cycle recovery in cells after x-ray irradiation]. AB - Alterations in the duration of mitotic cycle phases in X-irradiated HeLa cells after caffeine (CF) of allopurinol (AP) treatment are studied. Delays in S- and G2-phases, induced by 5 Gr of X-rays, are partially (1 mM) or completely (5 mM) decreased by both AP and CF. When the agent is removed from the medium, the delays are seen again. The data obtained enabled us to suggest a possible use of AP as a radiosensitizer in X-therapy of cancer transformations. PMID- 8009643 TI - [The repair of gamma-induced single-stranded breaks in the transcribed and nontranscribed DNA of HeLa cells]. AB - The repair of gamma-ray-induced DNA single-strand breaks (SSB) in transcribed (Alu-enriched DNA, proto-oncogene c-myc) and non-transcribed (human satellite III) DNA of HeLa cells has been investigated. A special methodical approach has been developed. The method involved alkaline sucrose sedimentation followed by Southern hybridization in situ of 32P labelled plasmids (probes) containing sequences analysed with total DNA distributed through sucrose gradient fractions. The degree of the probes hybridization with cellular DNA was the criteria of the damage and that of DNA repair. The induction of DNA SSB after irradiation (100 Gy) in Alu-enriched DNA and c-myc gene was shown to be 1.3-1.4 time more often while than in satellite DNA, and 1.4 time lower compared to that in total DNA. The rate of DNA repair was different: the most part of lesions was eliminated in the first 10-20 minutes in all cases. For this time 60-67, 50-66, 35-50 and 45 50% DNA SSB were eliminated from transcribed DNA (c-myc, Alu), non-transcribed DNA (satellite III) and total DNA, respectively. Thus, the preferable (fast) repair of gamma-ray-induced DNA SSB takes place in transcribed DNA compared to that in non-transcribed DNA of HeLa cells. PMID- 8009644 TI - Prevalence of coccidial infections in the West African Dwarf goat in the subhumid zone of Nigeria. AB - An investigation was made of the seasonal incidence of coccidial infection in West African Dwarf (WAD) goats in 2 villages and an on-station situation in the subhumid zone of Nigeria. Faecal samples were obtained from about 70 goats in each village and 160 on-station at 4 times of the year, early and late dry and wet seasons. Six species of Eimeria were found to occur; E. arloingi, E. apsheronica, E. pallida, E. alijevi, E. jolchievi and E. ninakohlyakimovae which accounted for 18, 16, 22, 9, 24, and 11% of infections respectively. Overall rates of infection were very high, averaging approximately 87%, and peaked during the late wet season, when the proportion of heavy infections also increased significantly. At this time the proportion of heavy infections classified as heavy was significantly higher in the village goats than the on-station goats, and was also significantly higher in kids than in adults. Clinical disease only occurred in kids. The potential benefits of controlling such infections in terms of productivity responses appear worthy of further investigation in these farming systems. PMID- 8009645 TI - DIAG, a laboratory information management system developed for regional animal disease diagnostic laboratories in Indonesia. AB - The DIAG Laboratory Information Management System is a micro-computerised program designed for the use of regional and national animal disease diagnostic laboratories in Indonesia. It facilitates the day to day management of diagnostic data by monitoring the progress and turn round times of samples sent to laboratory sections and by printing outputs detailing the tests undertaken and results obtained. Notifiable disease reports are generated routinely as part of a national disease surveillance programme. Detailed analyses of specific diagnoses allow investigations of diseases over location and time. The database is easily accessed to allow additional analyses. Data entry is facilitated through the use of entry screens which reduce associated errors. The system is flexible and can readily be adapted to meet the demands of different countries, veterinary services and types of laboratory. PMID- 8009647 TI - Effect of acaricide control of Amblyomma variegatum ticks on bovine dermatophilosis on nevis. AB - A sentinel group of 8 Bos taurus cattle was compared with similar cattle in a herd of 90 of which 21 were pastured with the sentinels. The sentinel group was not treated with acaricide whilst the rest of the cattle were treated weekly with the organophosphate acaricide ethion. Weekly counts of adult ticks and rankings of dermatophilosis were made on the sentinel herd. The remaining cattle were observed for the presence of ticks and dermatophilosis prior to the weekly treatment with acaricide. All sentinel cattle became infested with Amblyomma variegatum ticks and dermatophilosis developed on all. Rank correlations of tick numbers and dermatophilosis scores were between +0.34 and +0.98, varying with maturity of cattle and time during the trial. Incidence of dermatophilosis on the cattle treated with acaricide was very low. Tick numbers on the sentinel animals were compared to rainfall and temperature. It is concluded that acaricide is the best option for controlling bovine dermatophilosis in Nevis. PMID- 8009648 TI - Effect of suramin treatment on the productivity of feedlot cattle in a Trypanosoma evansi endemic area of Indonesia. PMID- 8009649 TI - Profitability of replacing milk with a concentrate for calves of cows requiring calf at foot for milking. AB - During a 90-d study in Mali, West Africa, 18 zebu and zebu by Montbeliard calves, age 50 +/- 23 d (youngest pair 3 weeks), weighing 30 +/- 7 kg, under farmer management, were used to test the profitability of replacing suckled milk by a maize-groundnut cake-rice bran concentrate fed dry. During the first 45 d period there were no differences in responses of calves receiving concentrate (E) and calves suckling according to the traditional strategy (C). During the second 45 d period, milk offtake was greater for E calves, 2.34 vs. 1.77 l/d; milk suckled was less for E calves, 0.39 vs. 0.95 l/d; and average daily gain was greater for E calves, 442 vs. 139 g/d. Average concentrate consumption was 0.74 kg/d. Concentrate was compounded of locally available byproducts and cost 85 francs/kg. Considering milk sold as the only benefit, net return to unit feed cost for E calves was 1.24 and for C calves 0.81. Adding the value of the weight gain, E calves gave a 1.61 return and C calves gave a 0.98 return. PMID- 8009646 TI - Control of tsetse flies in Uganda by dipping cattle in deltamethrin. AB - The effect of treating cattle with deltamethrin to control tsetse flies and ticks was investigated on 2 ranches 8 km apart in central Uganda where there is a high risk of trypanosomosis. This area had a moderate challenge of Glossina pallidipes. The cattle had very low challenge of Rhipicephalus appendiculatus, Amblyomma variegatum, Boophilus decolaratus and Rhipicephalus evertsi evertsi, due to regular treatment with dioxathion. On one ranch a dip was charged with deltamethrin to treat cattle regularly for 3 months. The other ranch was used as a control for the tsetse population, but the animals continued to be treated regularly with dioxathion using hand sprays. On the ranch using deltamethrin treatment a reduction of 96.9% in the tsetse population was recorded after 2 treatments at 2 week intervals. Total (100%) control of tsetse was achieved from the fourth treatment up to the end of the trial period. The ranch with dioxathion treatment experienced an overall tsetse reduction of 19.15% during the thirteenth to fifteenth weeks and the factors contributing to this are discussed. However, the mean apparent tsetse density of 4.83 flies/trap/day recorded at the control ranch was significantly different from the mean of 0.81 flies/trap/day (P < 0.001) at the ranch using deltamethrin treatment. It was difficult to assess the effect of this product on ticks because of lack of controls. However, there are indications that deltamethrin can also reduce tick populations and the incidence of tick-borne diseases. The possible limitations and practical implications associated with large scale use of this product in the country are discussed. PMID- 8009650 TI - Productivity of Boran cattle and their Friesian crosses at Abernossa Ranch, Rift Valley of Ethiopia. II. Growth performance. AB - Birth (4,197) and weaning (2,441) weight data on Boran, F1 Boran Friesian and three quarter Friesian calves as well as adjusted one-year (390), 2-year (177) and 3-year (364) weights on Boran cattle were analysed to estimate the influence of genetic and environmental factors. Boran, F1 and three quarter calves weighted 25.2, 25.4 and 25.7 kg at birth and 157.5, 176.7 and 179.9 kg at weaning, respectively. All factors included in the analysis and their interaction had significant effects on both traits with the exception of the effect of season of birth and its interaction with breed group on birth weight. Weight of Boran cattle at one-, 2- and 3-years of age were 179, 269 and 338 kg, respectively. Heritability values calculated on the basis of paternal half-sibs were 0.32, 0.24, 0.48, 0.29 and 0.24 for birth, weaning, one-year, 2-year and 3-year weights, respectively. The study indicated that F1 crosses were 12.2% heavier at weaning than Boran calves. Of the environmental factors considered, year of birth was found to be the major source of variation mainly due to variation in the amount of rainfall between years. PMID- 8009651 TI - Effect of liveweight and body condition on work output from draft oxen. AB - A trial was carried out to assess the effect of liveweight and body condition on working capacity of zebu oxen. Over a working period of 9 days, animals which started work with a mean liveweight of 360 kg and body condition score of M+ produced the highest daily work output (3.43 MJ). At an initial liveweight of 360 kg, body condition had relatively little effect on work output, and animals of condition score M- produced a daily work output of 3.19 MJ. In contrast, at a mean liveweight of 310 kg at the start of work, mean daily work output of animals of condition score M+ was significantly lower than that of animals in poorer condition (M-), at 0.81 compared with 2.50 MJ work output per day. It was concluded that body weight as indicated by body size is probably a more useful indicator of likely capacity for work than body condition under the short-season working conditions typical for oxen in the semi-arid zone of central Mali. PMID- 8009652 TI - Survey of pesticides used in the control of ectoparasites on farm animals in Ghana. AB - A study to identify the various types of pesticides used on farm animals in Ghana for the control of ectoparasites was conducted in 1989. Eleven organisations involved with pesticide use were questioned. Thirty organised farms and 110 kraals distributed throughout the 10 regions of Ghana were visited. Twenty different pesticides were in use. Of these 45% were organophosphates, 30% were synthetic pyrethroids, 15% were carbamates and 10% organochlorines. The most widely distributed and used pesticide was an organochlorine (lindane), which accounted for 35% of those used on farms and 85% used by herdsmen. The most popular mode of application was by hand dressing. No withdrawal periods before slaughter or sale of milk for consumption were practised. The implications of these findings in the light of possible emergence of pesticide resistance and health hazards are discussed. PMID- 8009653 TI - [Uncomplicated varices--a therapeutic problem?]. PMID- 8009654 TI - [Dementia--a diagnostic problem]. PMID- 8009655 TI - [Diagnosis of dementia--an objective examination or a subjective evaluation?]. AB - Case records of 404 elderly patients (aged 65 years or more) who were admitted for the first time to the Psychiatric Hospital in Aarhus, with a diagnosis of dementia were investigated retrospectively. In 315 patients the diagnoses were confirmed as senile dementia (290.09) or arteriosclerotic dementia (293.09) according to ICD-8. Eighty-seven patients had their diagnosis changed in the course of the case review. When case records of these 87 patients were investigated for the second time, four patients were diagnosed as demented: 66 patients were admitted because of confusion, 26 patients were diagnosed depressive, 10 of these manic-depressive. This investigation shows uncertainty and a tendency to overdiagnose of dementia, especially in the early stages. A wrong diagnosis may lead to therapeutic nihilism, especially when the patient suffers from confusion and/or depression. PMID- 8009656 TI - [Hazardous health effects of microwaves and radio waves]. AB - About 4000 Danish employees may be significantly exposed to radiofrequency electromagnetic radiation (RF) or microwaves (MW) during work in the health sector or industrially. Exposure measurements and classifications are difficult, therefore, epidemiological as well as experimental research in the field is complicated. High exposure induces elevation of body temperature or local heating ("hot spots"). Some biological effects from RF/MW exposure seem to be mediated by heating, others are considered to be athermic. Epidemiological studies do not indicate that RF/MW should be carcinogenic, and experimental studies have not shown the radiation to be mutagenic or carcinogenic. Epidemiological studies among physiotherapists have indicated that RF may have reproductive effects. In one study, an association between ischaemic heart disease and exposure to RF is observed. The cataractogenic property of MW is supposed to be mediated by elevation in lens temperature following relatively high exposure. However, in the light of the problems in exposure classification, the epidemiological research may not be conclusive, and attempts should be made to improve the methods. In addition, Danish experience points out a number of methods of exposure reduction in the working environment. PMID- 8009657 TI - [Aortic stenosis. Occurrence, pathogenesis, diagnostic strategy and therapeutic indications]. AB - Incidence, pathogenesis, diagnostic strategy and indications for treatment. Aortic stenosis is a serious disease which should be diagnosed early because of the good operative results. For this reason it is important to be aware of the disease particularly in the elderly and in patients with a history of rheumatic fever (e.g. immigrants). The diagnosis should be suspected in the patient with one or more of the three following symptoms: dyspnoea, angina pectoris and syncopes, and who has a systolic ejection murmur at the base of the heart with transmission to the neck and a reduced or absent second heart sound. First priority next to routine examinations (stethoscopy, ECG, x-ray of the chest) is referral to echocardiography. The echocardiographic results in combination with the patient's history and the clinical examination almost always form a sufficient basis for the timing of the operation. Indications for operation are given. PMID- 8009659 TI - [Bleeding disorders in women. Examination and treatment in general practice]. AB - To get an idea of how general practitioners (GPs) in Denmark normally deal with menstrual irregularities among their female patients a questionnaire was sent to 200 GPs in november 1992. One hundred and thirty-two answered the questionnaire, which mainly concerned the approach to oligomenorrhoea, secondary amenorrhoea, menorrhagia, metrorrhagia, spottings/postcoital bleeding and post-menopausal bleeding. They were also asked to specify differences in approach according to age of the patient. The uses of various examinations and treatments are encountered and discussed. It is concluded, that the use of Pap-smears in the diagnosis of abnormal bleeding should be further discussed. The widespread use of endometrial aspiration/dilatation and curettage in women with menstrual irregularities before the menopause should also be reconsidered. Further education is wished for by the GPs, and more research on this subject within general practice is recommended. PMID- 8009658 TI - [Sexual desire of middle aged women. A prospective study of women born in 1936]. AB - This study examines the nature of sexual desire experienced during hte climacteric and attempts to identify predictors for frequency and change of sexual desire using a prospective design. Four hundred and seventy-four women constituting 76% of the original cohort of a general population of Danish women born 1936 were examined by interview and questionnaire at the ages of 40, 45 and 51. Main items were sexual behaviour, expectations towards/experience of menopause, general health status and social background. Most women (70%) experienced no change in sexual desire during the study period. The 51-year-old women's experience of frequency or change in sexual desire was not related to menopausal status. Frequency of sexual desire was highly correlated to previous and present subjective health status, former sexual activity, partner availability and social status. Finally, anticipations of declining sexual desire as a consequence of menopause actually predicted a decrease. PMID- 8009660 TI - [99mTc anti-carcinoembryonic antigen in colorectal cancer]. AB - This investigation is a part of a phase three multicentre immunoscintigraphy study of a technetium-99m labelled monoclonal antibody (Mab), BW 431/26, directed against carcino-embryonic antigen (CEA). Ten patients with recently colonoscopically verified primary colorectal cancer were evaluated. In nine of ten patients colorectal cancers were detected by wholebody immunoscintigraphy and by single photon emission computerized tomography (SPECT). The ten patients were operated upon, and in nine cases immunohistochemical investigations were performed. Immunohistochemical investigation of nine tumour specimens show that CEA was present in much higher concentrations in the tumour than in normal intestinal epithelium. Active accumulation of the labelled Mab in tumours was demonstrated by scintimetry. There is a demand for new diagnostic techniques for early diagnosis of colo-rectal cancer. Immunoscintigraphy must however compete with other diagnostic possibilities. The development of immunoscintigraphic technique is proceeding very rapidly, and there is probably a future for the use of immunological methods in diagnosis and therapy of cancer. PMID- 8009661 TI - [Intrathoracic goiter. Diagnostic aspects, surgical complications and permanent sequelae]. AB - During the course of 1151 thyroidectomies performed during an 11-year period, 195 patients were found to have intrathoracic goitre. Centre experience of operating this disease and the usefulness of applied diagnostic methods are analysed. The sensitivity of physical examination (palpation), technetium scintigraphy and chest roentgenogram is respectively 52%, 33% and 65%, while specificity is respectively 99%, 98% and 95%. These three methods together ensure the diagnosis in 82% of the patients. Positive predictive values are respectively 95%, 78%, and 72%, while negative predictive values are found to be 91%, 89%, and 93%. Frequency of permanent unilateral vocal cord paresis is 2.5%, no cases of bilateral recurrent nerve damage occurred. The frequency of unilateral vocal cord paresis is found to be 1.4%, if nerves of risk are considered. The incidence of hypocalcemia requiring permanent treatment reaches 2%. Intrathoracic goitre can be treated surgically with an only slightly elevated risk for surgical complications and permanent sequelae, especially when performed in the elective phase and within the frame of centre facilities. Intrathoracic components can nearly always (97%) be reached through cervical incision. PMID- 8009662 TI - [Malignant lymphoma of the heart]. AB - A case of malignant lymphoma in the heart is presented. A 75-year-old man was admitted to hospital for dyspnea. Echocardiography revealed a right atrial tumour and enlargement of the right ventricular wall. Myxoma was suspected clinically. The patient died from rapidly progressing congestive heart failure. Autopsy revealed massive infiltration of the myocardium in the right atrium, right ventricle and the tricuspid valves by a high grade malignant non-Hodgkin lymphoma of B-cell type. Malignant lymphoma was found at no other sites except for a five mm tumour in the thyroid gland and a larger six by five by four cm mediastinal tumour. PMID- 8009663 TI - [Behcet syndrome]. AB - Behcet's syndrome (BS) was first described in 1937 as the triad of recurrent oral and genital ulcerations and iritis. BS is a systemic, inflammatory disease of unknown etiology characterized by multiorgan vasculitis. The long-term prognosis is often good, but the disease may lead to blindness and serious neurological sequelae. The broad clinical spectrum of the disease and the lack of pathognomonic lesions make the diagnosis difficult, especially in children. We report a case of BS in a child, and based on a review of the literature we describe the present diagnostic criteria, new immunological aspects, clinical course, and current therapy of the disease. PMID- 8009664 TI - [European guidelines for quality assurance in the screening for cancer of the uterine cervix]. PMID- 8009665 TI - [Retinoid therapy of acute promyelocytic leukemia]. PMID- 8009666 TI - [Quality of life and disease]. PMID- 8009667 TI - [Respiratory syncytial virus--a severe pathogen in Danish children]. PMID- 8009668 TI - [Respiratory syncytial virus infection. A frequent child disease in Denmark with annual outbreaks]. AB - Infection with respiratory syncytial virus (RSV) is an important cause of illness in infants often leading to hospital admission during the winter months. Diagnosis of RSV by direct detection of virus antigen has been implemented in a number of departments of clinical microbiology, and on this background a descriptive study of the seasonal incidence, sex and age distribution of RSV in two Danish counties was undertaken. A total of 5533 clinical episodes of respiratory infection were registered from October 1988 to September 1992 in the two counties and 1421 (26%) were positive for RSV. The incidence of hospital admission for RSV infection was 14 per 1000 below three years of age in Copenhagen County in the winter season 1991-1992. The seasonal peak of RSV infection was postponed about one month in Northern Jutland as compared to the capital area. Only 10 episodes (three positive) were from primary care, the remainder from hospitals and other institutions. RSV-testing was rarely requested in general practice. The study confirmed the importance of RSV infection in young children admitted with lower respiratory tract infection. We recommend the establishment of a surveillance system incorporating the local departments of clinical microbiology for warning of the yearly epidemics during which RSV infections may also be a risk outside the paediatric age span. PMID- 8009669 TI - [Complications of epidural bupivacaine analgesia in vaginal labor]. AB - Epidural analgesia is accepted as a good and effective method of analgesia in labor. The method is, however subject to a variety of complications, the worst being life long sequelae and death. The article presents a survey of the complications of bupivacaine epidural analgesia in labour and state prophylactic measures and treatments. The existing literature on the field is commented and criticized. PMID- 8009670 TI - [The role of social factors in the place of death of cancer patients in the county of Nordjylland]. AB - The purpose of this study was to evaluate the importance of social factors on whether cancer deaths occurred at home or in hospitals. The study was based on questionnaires to the patient's general practitioner and to the home nursing service. The study included 241 patients with terminal cancer who were all identified by death certificates via the Department of Public Health in the period of the 1st February, 1992 to the 31st April, 1992. The study demonstrated that significantly more patients died in their own homes when a contact to the home nursing service had been established. The same tendency could be observed for patients with relatives being reimbursed for loss of income while providing care in the home. Significantly more patients died at home in municipalities where 24-hour nursing facilities could be offered. No association between age, sex, or whether the patient lived alone or lived cohabitantly were observed. The study suggest that an intensification of the home nursing facilities would give a greater number of terminal cancer patients the option of dying in their own homes. The possibility of relatives being reimbursed for loss of income while providing care in the home has a positive influence on the development of the number of cases home nursing. PMID- 8009671 TI - [Greenlanders in hospital. An interview study of communication between patients and therapists, satisfaction and therapeutic preferences]. AB - In four hospitals in Greenland, 50 Greenlandic patients and their Danish therapist (18 doctors, 26 nurses and six other staff) have been interviewed about the same topics. The interviews were semistructured with open ended questions on the following subjects: Language difficulties, perception of diagnosis and therapy, patients' satisfaction and points of criticism. Several of the patients had not understood the most important medical information about diagnosis and treatment. But most of the patients did not consider the information problem to be serious and patients were satisfied with most of the consultations. Language difficulties and insufficient communications do not correspond to patients' satisfaction but have to be analysed in the wider cultural context. There was a tendency towards the elder patients being more satisfied than the younger. PMID- 8009672 TI - [Greenlanders' attitudes towards health and disease. A comparative interview study of patients' and therapists' attitude to disease and health]. AB - In four hospitals in Greenland, 50 Greenlandic patients and their Danish therapists (18 doctors, 26 nurses and six other staff) have been interviewed about their perceptions of disease and treatment and experiences of health in general. The Greenlandic patients' experiences of health were different and sometimes more articulate than those of their Danish therapists. Most of the Greenlandic patients expressed a trusting relationship towards the therapists, but most of the Danish professionals experienced that attitude as being authoritarian and dependent. It does not seem to be necessary in order to achieve a good treatment result that the patients and their therapists speak the same language and share the same concepts of health and disease. In those cases where the foreign health service's offers of treatment can be contained, and are not experienced as a threat to culturally related concepts of disease, the consultation presumably results in the best patient satisfaction. PMID- 8009673 TI - [The value of routine radiography after treatment of pneumothorax]. AB - The present study evaluates the value of a routine outpatient chest X-ray and clinical control of patients treated for pneumothorax one week after discharge from hospital. It was a retrospective study including 262 patients admitted to Frederiksberg Hospital during the 10-year period 1980-89. Follow-up was possible in 100 patients. Among these 100 there were 30 cases of recurrence in 20 patients. None of the recurrences were presented at the control. Mean time to recurrence was 23.4 months, the first recurrence was observed after one month. It is concluded that the out-patient roentgenological and clinical control one week after discharge after treatment for pneumothorax seems unnecessary. PMID- 8009674 TI - [Tall girls]. AB - Over a period of 17 years, 17 girls with excessive height were referred to a private paediatric practice. Among 14 one or both parents were very tall. Eleven girls had already reached an excessive height before school age. Mean age at the time of examination was 12.3 years and mean bone age 13.1 year. Menarche had occurred in six girls. The mean final height was estimated to 181 cm according to the method of Tanner et al. It is concluded that at least half of the girls were investigated too late with regard to the optimal time of oestrogen treatment. If this treatment is to be considered in girls with tall parents who grow fast at an early age their final height should be estimated earlier, i.e. at an age of 10-11 years. PMID- 8009675 TI - [A short discharge letter with a copy to the patient--satisfactory for patients and practitioners]. AB - This study evaluated the introduction of a new type of discharge letter (DL). The new DL is hand-written by the discharging doctor on a form, and a copy is both given to the patient and sent immediately to the general practitioner (GP). Questionnaires were sent both to the receiving patients and GPs. One hundred and thirty-four patients (55%) and 157 GPs (87%) replied to the questionnaires. Half of the responding patients stated that the DL had helped them to understand what had happened during their hospital stay, as well as future plans for treatment. A majority of the responding GPs found the hospital stay, the patient's status at discharge and the planned after treatment to be satisfactorily described in the new DLs. Almost all GPs (90%) were pleased with the promptness with which they received the new DL. Compared to the traditional DL, 40% of the responding GPs found the new DL to be better and 29% found it to be worse. PMID- 8009676 TI - [Immunological techniques in unexplained thrombocytopenia. A case of specific diagnosis of post-transfusion purpura]. AB - A case of post-transfusion purpura is presented. The diagnosis is based on two new techniques with immunological aspects: 1) Monoclonal Antibody Immobilization of Platelet Antigen assay (MAIPA-assay) and 2) Polymerase Chain Reaction assay (PCR-assay). MESH: Thrombocytopenia. Post-transfusion purpura. Monoclonal Antibody Immobilization of Platelet Antigen assay (MAIPA-assay). Polymerase Chain Reaction assay (PCR-assay). PMID- 8009678 TI - [Hemangiopericytoma. A rare vascular tumor with complicated operative and postoperative course]. AB - Haemangiopericytoma (HPC) is a rare soft-tissue vascular neoplasm that may arise in almost all parts of the body. This report describes a 62-year-old man with one of the largest retroperitoneal HPC ever described weighing 950 grams. The surgical excision was followed by severe haemorrhages demanding several operations. The postoperative course was very complicated and prolonged. The geriatric rehabilitation was successful. PMID- 8009677 TI - [Complete invasive mole in a 50-year old woman]. AB - A 50-year-old woman was admitted for hysterectomy due to persistent vaginal bleeding and enlargement of the uterus. Before operation a significant increased beta-HCG was measured. Histologic examination of uterine contents obtained by aspiration showed trophoblastic disease. An decrease in beta-HCG was registered postoperatively. However, two weeks later it rose again and the patient started treatment with methotrexate. It is recommended that the treatment of patients with invasive gestational trophoblastic disease is centralized. PMID- 8009679 TI - [Danish Society for Thrombosis and Hemostasis]. PMID- 8009680 TI - [How to prevent the spreading of respiratory syncytial virus in pediatric departments?]. PMID- 8009681 TI - [Excessive mortality in relation to weight loss]. PMID- 8009682 TI - [Sore throat--who should be treated?]. PMID- 8009683 TI - [Streptococcal tonsillitis: failure of penicillin therapy]. AB - Group A beta-haemolytic streptococci (GAS) have remained sensitive to penicillin, but penicillin V therapy does not eradicate GAS in 5-30% of cases of GAS tonsillitis. Multiple factors contribute to treatment failure, the foremost among these being lack of compliance with the prescribed therapy, tolerance of GAS towards the killing effect of penicillin, inactivation of penicillin by bacterial beta-lactamases, and absence of bacteriocin-producing non-haemolytic streptococci from the oral flora. The effect of local immunity should be further assessed. It is unlikely that environmental sources of GAS play any significant role. Throat cultures should not routinely be repeated after penicillin treatment. If, in special cases, a new course of treatment is indicated, penicillin V should still be preferred. In the light of modern pharmacological insights, multiple dosing schedules may be desirable in the therapy of GAS tonsillitis. PMID- 8009684 TI - [AIDS and heart disease]. AB - This article reviews cardiac manifestations of AIDS in terms of etiology, pathogenesis, pathoanatomic lesions and heart function. Hypothetically the prevalence of myocarditis and disperse fibrosis of the myocardium are correlated to increasing rates of dilated cardiomyopathy and cardiac insufficiency. Echocardiography has proved to be of value in detecting early abnormalities and should be recommended on broad indications, though aggressive therapy of cardiac abnormalities is of importance to ensure quality of life and surveillance for the patients. PMID- 8009685 TI - [Long-term prognosis in patients with acute chest pain. The predictive value of myocardial scintigraphy]. AB - In order to perform risk stratification 158 patients with acute chest pain, but without myocardial infarction (non-AMI) underwent exercise 201-thallium scintigraphy at the time of discharge. The patients, of whom 38 (24%) were women, were followed for seven years. The diagnostic sensitivity, specificity and predictive values of the outcome of the examination for identification of patients, who had a cardiac event (cardiac death or later non-fatal AMI) during follow-up, was calculated. Forty-one had a cardiac event during follow-up. The highest sensitivity (85%) was achieved by the combination of transient defect and/or persistent defect and/or abnormal ST-segment response. The highest specificity was provided by a transient defect (90%) and the predictive value of a positive test was 60%-17 of 29 patients with a transient defect had a cardiac event during follow-up. Patients with a normal test had an excellent prognosis, 94% of 82 patients were free of cardiac events during follow-up. CONCLUSIONS: Exercise 201-thallium scintigraphy is suitable for long-term risk stratification in patients with chest pain and suspicion of but unconfirmed myocardial infarction, because high and very low risk subsets can be identified at the time of discharge. PMID- 8009686 TI - [Data and quality assurance tools from a new cardiac center in Denmark]. AB - Open heart surgery was established at Aalborg Hospital in 1992. In the time period March to December 1992 cardiac anaesthesia was administered in 98 operations utilizing extracorporeal circulation and cardiopulmonary bypass. Mortality in coronary artery surgery was 1.6%. All patients were prospectively registered using a new dataform allowing registration of 228 patients related variables concerning preoperative status, course of anaesthesia and perfusion, surgery and postoperative intensive care. Quality assurance in cardiac surgery requires risk factor analysis, and registration of numerous data is a necessary tool. The software for our database system has been developed and programmed using the database programme dBASE IV from the Ashton/Tate Corporation. PMID- 8009687 TI - [Staffing the emergency departments]. AB - In recent years, there has been a growing public demand that the emergency department (ED) should be staffed by an orthopaedic surgeon. We questioned the necessity of this, and here present a prospective study of 4500 consecutive patients attending the ED of Naestved Hospital. About 70% of the patients were found to have injuries or ailments that belonged to the orthopaedic specialty, and were treated by doctors from this department, but only 15% of these cases required treatment by a specialist in orthopaedic surgery. The remaining contacts to the ED concerned cases belonging to other specialties. Eight percent of all contacts resulted in admission, half to the orthopaedic ward and half to other departments. In conclusion, about 60% of all cases could be treated by any doctor, and the ordinary physician would in actual fact be able to treat more cases than the orthopaedic surgeon with at least as good a result. Thus, we question whether the orthopaedic surgeon is the best person to be in charge of the ED. PMID- 8009688 TI - [Arthroscopy of post-traumatic shoulder pain]. AB - Thirty-two consecutive patients suffering chronic shoulder pain for more than six months after a non-dislocating shoulder trauma were examined clinically and with arthroscopy of the shoulder. The trauma was blunt or simple distortion of the shoulder. The patients complained of pain during loading, especially during over the head activities. Symptoms of dead arm and feeling of instability with a popping sensation inside the shoulder were also present. Patients with previous dislocations, trauma or radiographic signs of degenerative shoulder lesions were excluded. Clinically, 21 patients had decreased range of motion, 19 patients had a positive anterior apprehension sign and four of these had signs of shoulder instability. Nine patients had signs of impingement. The suspected preoperative diagnoses included a tear of the rotator cuff (17), a tear of the labrum (12), tendinitis of the biceps tendon (2) and periarthrosis of the shoulder (1). Arthroscopic findings consisted of 22 labral tears, six partial and three total rotator cuff lesions and three cases of synovitis of the rotator cuff with signs of subacromial impingement. Four patients had tendinitis of the biceps tendon. One patient had a lesion of the greater tubercle. Only two shoulders were found to be unstable under anaesthesia. In conclusion, patients with posttraumatic chronic shoulder pain after a non-dislocating trauma of the shoulder should be evaluated with arthroscopy in order to diagnose possible intraarticular lesions. PMID- 8009689 TI - [Safety in using metal tracheostomy tubes]. AB - The breakage of a stainless steel tracheostomy tube resulted in the death of a 19 year old man. Technical investigations identified corrosion as the mechanism of degradation of the braced joint between the plate and the external tube. Examination of a stock of 112 sterling silver tubes showed corrosive attacks on four tubes. Recommendations are presented concerning the production, maintenance and control of metal tracheostomy tubes. PMID- 8009690 TI - [Screening of school children for familial hypercholesterolemia]. AB - A total of 3025 families with school children aged six to eight years were offered pilot screening for familial hypercholesterolaemia by measurement of the concentration of apolipoproteins A-1 and B in the children's capillary blood and by analysis of their family histories of early ischaemic heart disease. The concentrations of the apolipoproteins were determined by double rocket immunoelectrophoresis of an eluate of blood spotted on filter paper. Results were available from 2085 children. Because their B:A-1 ratio was above the 97.5 centile and their concentration of B was above the 99th centile, 54 children (2.6%) were selected to have their apolipoprotein concentrations reassessed. The 17 children (0.8%) whose values were persistently above the chosen cut-off points, and all of their available first and second degree relatives, had fasting determinations of serum lipid concentrations carried out. Raised serum concentrations of low density lipoprotein cholesterol and an autosomal dominant pattern of hypercholesterolaemia were found in respectively 12 children and 10 families, suggesting a higher incidence of familial hypercholesterolaemia than the reported 1:500. Further investigations among family members disclosed hypercholesterolaemia in 29 relatives. A family history of early ischaemic heart disease was elicited by questionnaire, and was positive in only five of the 12 school children with hypercholesterolaemia. We conclude that analysis of apolipoproteins from capillary blood spotted on filter paper is suitable for screening for familial hypercholesterolaemia, and that this method is more efficient than screening based on family history. PMID- 8009692 TI - [Macrocytic anemia in the last trimester of pregnancy due to dietary insufficiency--initially interpreted as the HELLP syndrome]. AB - A case of severe macrocytic anaemia caused by cobalamin and folic acid deficiency in a 32 year-old gemellipregnant woman in gestational week 32 +2 is described. Her symptoms and the laboratory data were initially interpreted as HELLP-syndrome (haemolysis, elevated liver enzymes and low platelet count), and caesarean section was performed. None of the persons involved in her earlier prophylactic controls suspected anaemia, and no specific dietary advice were given. If she had received dietary advice early in the pregnancy, anaemia could have been avoided. This emphasizes the need for dietary advice early in pregnancy. PMID- 8009691 TI - [Treatment of Bartholin's abscess. Marsupialization versus incision, curettage and suture under antibiotic cover--a randomized trial with a 6-months follow-up]. AB - Treatment of Bartholin's abscess with incision and curettage of the cavity suture under antibiotic cover reduces the average healing time compared with conventional marsupialization. Recurrences were not more frequent after suture. PMID- 8009693 TI - [Rapid postnatal diagnosis of Down syndrome]. PMID- 8009694 TI - [Indications for in vitro fertilization (IVF) at the public fertility clinics]. PMID- 8009695 TI - [Colonoscopic polypectomy reduces the risk of colorectal cancer]. PMID- 8009697 TI - [Exercise is the best medicine]. PMID- 8009698 TI - [Vasectomy: who regrets it and why?]. AB - In order to determine the real percentage of sterilised men who regretted their sterilisation and for which reasons, a retrospective questionnaire survey was conducted in 1990-1991 on 244 men sterilised between 1980 and 1983. Information was also collected from their case records. 7.4% of the sterilised men regretted their decision. Of these, 39% were younger than 30, and 94% had started a relation with another woman. The lower age limit for sterilisation according to the law is 25 years, 37% found this age limit too low and 6% found it too high. We conclude that it should be considered whether the legal lower age limit for sterilisation is too low. It is important to thoroughly inform the patient about problems in sexual relations and alternative methods of contraception before he decides on sterilisation. PMID- 8009696 TI - [Vasectomy]. PMID- 8009699 TI - [Vasectomy using the Li method]. AB - The no-scalpel vasectomy is described and evaluated. Nineteen out of 21 consecutive patients could be operated with this technique. The median operating time was 16 minutes, range 9-50 minutes. There were no complications and the scar was barely visible after ten days. The median score for pain was 0.4 cm (range 0.0-5.0 cm) and for discomfort 0.7 cm (range 0.0-5.0 cm) on a 10 cm long visual analogue scale. The method is minimally invasive and well-tolerated by the patients. When some routine is gained the operating time is short. PMID- 8009700 TI - [Intensive multidisciplinary treatment of back pain--2 controlled prospective studies]. AB - The aim of this study was to evaluate an intensive, multidisciplinary functional restoration program for people with chronic low back pain. The program was compared to a non-treated control group in project A, and to less intensive treatment programs in project B. Both projects were randomized and observer blinded. Two hundred and thirty-eight patients were included, 106 entering project A and 132 project B. All had had chronic low back disability of at least six months duration, with an average of one year's sick leave due to low back pain over the last three years. Their average age was 41 years. The results at follow-up (conducted four months after treatment, follow-up rate 90% in project A and 86% in project B) showed that 67% of the treated patients in project A were able to work compared to 28% in the control group. In project B, 75% of the patients treated in the functional restoration program were able to work, the corresponding numbers from the less intensive programs being 48% and 40%. Numbers of days of sick leave, contacts to the health-care system and pain- and disability-scores were significantly lower for the patients treated in the functional restoration program compared to the other groups in both projects. Functional restoration is more expensive to carry out, but the long-term benefits in form of reductions in pensions, sick leave and contacts to the health-care system, not to mention reduced pain for the patients, seems to justify this expenditure. PMID- 8009702 TI - [Arthritis urica. Clinical picture, diagnosis and treatment]. AB - Gout is an acute episodic monarthritis or chronic pauci- or polyarticular arthritis. The symptoms of gout are induced by monosodium-urate crystals that are liberated from accumulations in connective tissue structures, primarily cartilage. Deposition of monosodium-urate crystals is caused by hyperuricaemia, which is dealt with in a previous paper. Only a minority of persons with hyperuricaemia develop gout, however. The diagnosis is based on detection of urate crystals in synovial fluid or tophi. Acute gout is treated with antiinflammatory agents, primarily NSAIDs or colchicine. Predisposing diseases and associated conditions such as hypertension, diuretic drugs, overweight and nephropathy should be controlled as well as possible. In patients with recurrent attacks of acute gout or chronic gout, treatment with urate lowering drugs, principally allopurinol, should be given. Treatment with allopurinol should be adjusted according to levels of serum urate and renal function. Serious complications to allopurinol treatment have been described. PMID- 8009701 TI - [Hyperuricemia]. AB - Uric acid is formed by catabolism of purine nucleotides. Approximately 25% is excreted through the intestines and the rest through the kidneys. A little less than 5% of the population in western industrialised countries have hyperuricaemia, primarily men and postmenopausal women. Hyperuricaemia is in most cases caused by reduced renal excretion, which may be idiopathic with otherwise normal renal function. But the condition is often associated with hypertension, nephropathy and treatment with diuretics and certain other drugs. Hyperuricaemia due to increased purine metabolism is seen in malignant haematological diseases, other conditions with increased cellular turnover and during initiation of chemotherapy in malignant diseases. Moreover hyperuricaemia is associated with some metabolic disturbances and risk factors of atherosclerotic cardiovascular disease including hypertension, overweight, insulin resistance and hyperlipidaemia. Hyperuricaemia is rarely caused by constitutional enzymatic abnormalities influencing purine metabolism. In most cases hyperuricaemia is asymptomatic. It may though be complicated by gout, urolithiasis and possibly gouty nephropathy. The risk of complications is correlated to the degree and duration of hyperuricemia. Consequently, measures to affect predisposing and associated conditions should be taken including weight reduction, physical exercise and diet guidance, treatment of hypertension and possibly changes in medication. Urate lowering drug treatment is normally not indicated in asymptomatic hyperuricaemic individuals. PMID- 8009703 TI - [Does intake of antihypertensive agents and sedatives explain the increasing incidence of colonic neoplasms?]. AB - Not much attention has been given to drug use and risk of colorectal cancer. We investigated the issue in an 18-year prospective cohort study of 5249 Copenhagen males aged 40-59 years. Potential confounders included were tobacco smoking, alcohol consumption, coffee drinking, physical activity, and social class. Colon cancer was diagnosed in 51 men, rectal cancer in 42 (all adenocarcinomas). Estimated from a Cox proportional hazards regression equation, use of antihypertensive medicine was highly significantly associated with risk of colon cancer, relative risk (95% confidence limits) was 3.5 (1.6-7.5), p = 0.001. Frequent use of minor tranquillizers or sleeping pills was also associated with a highly significantly increased risk of colon cancer, relative risk was 3.2 (1.6 6.6), p = 0.002. By contrast, there was no such association with rectum cancer. We suggest that use of antihypertensive medicine and use of minor tranquillizers or sleeping pills may be strong risk factors for colon cancer, and that their use may contribute substantially to explaining the increased incidence of colon cancer since 1945. PMID- 8009704 TI - [Acute epiglottitis. 27 years of experience with and future development of nasotracheal intubation]. AB - During a 27-year period 295 patients in Copenhagen County were treated for acute epiglottitis. One hundred and eight-two were adults and 113 were children. Most children were treated by nasotracheal intubation while only a few adults required nasotracheal intubation in order to secure the airway. The incidence of acute epiglottitis in children less than five years old was calculated to be 8.7/100,000 with minor annual variation. Since vaccination against Haemophilus influenzae type b has been implemented in Denmark from May 1993, this figure will probably be markedly reduced, and the disease even may be even eradicated in children, but in adults the same reduction cannot be expected as the causative agent in this group is less frequently Haemophilus influenzae type b. It is emphasized that this reduced incidence will make it even more important that each department engaged in the treatment of suspected acute epiglottitis have a departmental protocol for management of the condition, so that the future rarity of acute epiglottitis does not cause the mortality rate to rise. PMID- 8009705 TI - [Exogenous estrogens and risk of breast cancer]. PMID- 8009706 TI - [Hardly any association between vasectomy and prostatic cancer]. PMID- 8009707 TI - [Hearing loss in extremely premature children]. PMID- 8009709 TI - [Bone marrow examination]. PMID- 8009708 TI - [Blindness in premature children]. PMID- 8009710 TI - [Surgery requires evaluation!]. PMID- 8009711 TI - [Needles for bone marrow examination]. AB - Over the past decades, numerous new bone biopsy needles have been introduced. Pathological investigation requires sufficiently large and well-preserved specimens. This article reviews the literature concerning the quality of the instruments. Comparison of the various types of needles in controlled studies is not available. Bone-marrow biopsy is discussed in the context of obtaining optimal specimens and choice of biopsy needle. PMID- 8009712 TI - [Asperger syndrome. A new diagnosis in the international classification of diseases]. AB - Asperger's syndrome (AS) is a new diagnosis in the 10th edition of International Classification of Diseases (ICD-10). AS is closely related to infantile autism and belongs to the so-called pervasive developmental disorders. The characteristics of the disorder are qualitative abnormalities in reciprocal social interaction, restricted and repetitive patterns of behaviour and interests and often motor clumsiness and problems with nonverbal and social aspects of communication. The sex ratio is about eight boys to one girl and the prevalence among schoolage boys is about 0.3%. The abnormalities normally persist into adulthood. Early diagnosis and a combination of social, educational and psychiatric interventions are necessary to relieve the stress on the person with AS and his family. Differential diagnoses and assessment are discussed. PMID- 8009713 TI - [Breast cancer in the county of Viborg during 1983-1989. A quality control study]. AB - The aim of the present study was to compare the quality of treatment for breast cancer in Viborg County to that provided in the rest of Denmark during the period 1983 to 1989. Women younger than 70 years of age with the diagnosis of invasive breast carcinoma and registered in the DBCG (Danish Breast Cancer Cooperative Group) were included, 435 from Viborg county and 11,434 from the rest of Denmark. No differences were found between the two patient-groups with regard to tumoursize, degree of anaplasia, number of axillary lymph nodes removed or number of positive lymph nodes. There were also no differences in overall survival or recurrence-free survival (RFS). It was concluded that the quality of treatment for breast cancer in Viborg County was equal to that in the rest of Denmark. Moreover, the magnitude of registration of breast cancer patients in the DBCG from Viborg county was evaluated. More than 90% of all breast cancer patients were registered. PMID- 8009714 TI - [Ultrasound and lymphography in malignant lymphoma. Comparison with consideration to staging]. AB - The diagnostic value of abdominal ultrasound and lymphography was compared in the staging of 88 consecutive patients with malignant lymphoma, examined during the period March 1990 to April 1991. Lymphography was used as the reference method in the evaluation of the paraaortic and iliac lymphnodes. In 19% of the patients ultrasound examination could not be accomplished optimally, and these results were evaluated in a separate group. Lymphography demonstrated involvement of retroperitoneal lymphnodes in 27 patients, among these ultrasound was false negative in seven (= 26%). In ten patients ultrasound examination demonstrated lymphoma outside the lymphographic area. No false positive ultrasound examinations were found in the group with negative lymphography. Ultrasound cannot replace lymphography, but is an important supplement, and in those cases where ultrasound reveals lymphomas in the lymphographic area, lymphography can be omitted as ultrasound has a high predictive value. PMID- 8009715 TI - [Plasmin-mediated activation of the coagulation system. A study of patients with acute ischemic heart disease treated with recombinant tissue-plasminogen activator]. AB - We have studied the response of haemostatic reaction products in peripheral blood of patients with acute ischaemic heart disease receiving combined recombinant tissue type plasminogen activator/heparin therapy. We have found evidence that formation of excessive amounts of plasmin in vivo in relation to such therapy significantly enhances the degradation of fibrin, and of fibrinogen as well as the formation of thrombin. We conclude that excessive plasmin formation by thrombolytic therapy causes systemic effects including activation of coagulation. PMID- 8009717 TI - [Do surgical procedures contribute to women's risk of developing urinary incontinence?]. AB - In a cross-sectional study, 85% of 3114 women responded to a questionnaire on urinary incontinence and a history of abdominal, gynaecological and urological surgery. The prevalence of urinary incontinence was 17%; 63% had undergone surgery, mainly gynaecological, and almost one-third of the respondents had had more than one operation. Bivariate and multivariate analysis showed stress urinary incontinence to be associated with previous exposure to surgery. PMID- 8009716 TI - [Laparoscopic appendectomy. Results and complications]. AB - Thirty-four patients (23 females and 11 males) aged 13-71 years had acute appendicitis on both clinical and laparoscopic evaluation. Twenty-eight patients (82%) were treated laparoscopically whereas conversion to open appendectomy was necessary in six patients. Operation time for laparoscopic appendectomy ranged from 25-90 min. (mean 58 min.), and the patients were discharged 1-14 days after the operation (mean 2.8 days). Five patients developed complications, wound infection in one case, intraperitoneal infectious complications in three cases and postoperative fever in one case. Mean convalescence was two weeks. All patients were satisfied with the performed procedure and the cosmetic result and all were doing well one month after the operation, except for one patient who had pain in the right iliac fossa. The initial results of laparoscopic appendectomy are promising. PMID- 8009718 TI - [Hashimoto thyroiditis and malignant disease of the thyroid gland]. PMID- 8009719 TI - [Knee joint arthroscopy--a rough "double-selection"]. PMID- 8009720 TI - [Scientific "ethics" and free research]. PMID- 8009721 TI - [Organ donation]. PMID- 8009722 TI - [Attitude of the population to organ transplantation]. AB - The attitude of the Danish population towards organ transplantation was examined by means of an interview study, executed by the Gallup Institute. From a sample population of 1391 persons above 18 years of age, 798 persons (70%) were interviewed, in the period April 24th to May 3rd 1992. When asked what they thought the general attitude toward transplantation was amongst the population, 65% answered "positive" or "very positive". The attitudes to three situations, namely to organ donation after the death of a parent, spouse or child was examined subsequently. Amongst those who had an opinion, 75% (72-76%) were positive and 25% (24-27%) were negative. The younger the interviewed person, the more positive the attitude. According to the Danish law the relatives can decide for or against organ donation if the deceased has not expressed her view on organ donation. In view of the general positive attitude of the population it is proposed that we introduce a system where every adult person is asked concerning his/her attitude, e.g. in connection with the yearly income tax form or renewal of the health insurance certificate. PMID- 8009723 TI - [Cannabis and psychoses]. AB - Patients with the combination of cannabis abuse and psychosis are difficult to treat. The intoxicated state has many similarities to schizophrenia. Like other drugs with abuse potential cannabis affects the brain's reward system. It has not been possible to show major structural changes in the cerebrum, but by electron microscopy structural changes can be shown in animals especially in the hippocampus. The drug is taken in order to escape reality, and a vicious circle tending to maintain the person's abuse pattern which includes reduced energy, judgment and memory may be established. Cannabis may cause toxic psychosis, with a tendency to recurrent psychoses with continued abuse. There is no convincing support for the assumption that cannabis can cause chronic functional psychosis following cessation of abuse. Schizophrenic patients who use cannabis are often trying to reduce the discomfort caused by symptoms in the prodromal phase. By continued abuse positive psychotic symptoms are worsened. Antidepressant drugs may diminish the depressive elements of the disease. Some cannabis users are especially sensitive and develop toxic psychosis. Patients with repeated toxic psychosis may erroneously be diagnosed as schizophrenics. It is therefore important to be aware that a psychotic state may be caused by abuse of cannabis, and adjust treatment to this fact. PMID- 8009724 TI - [Diagnostic possibilities and strategy in the detection of liver metastases]. AB - The value of laboratory tests, scintigraphy, angiography, ultrasonography (US), computed tomography (CT) and magnetic resonance imaging (MR) in the detection of hepatic metastases is evaluated through a review of the literature. The diagnostic value, advantages, disadvantages and limitations of each test are discussed separately. The discussion also includes, economic aspects such as costs, time consumption and examination capacity as well as invasiveness, side effects, use of contrast medium and patient tolerance. Based on an over-all evaluation, high-quality US combined with US-guided needle biopsy is recommended as the first-choice examination in the detection of liver metastases. In cases of doubt, CT with intravenous contrast and CT-guided biopsy are advisable as a supplement to US. For assessing the effect of treatment, CT is the most suited modality because of its reproducibility. In planning a resection of the liver, detailed information about the localization, size and extent of each lesion is required. Under these circumstances a combination of angiography, CT (or MR) and intraoperative US is to be preferred. PMID- 8009725 TI - [Epidemiology of acute wrist injuries]. AB - Epidemiological data on wrist injuries in a population can be used for planning by applying them to criteria of care and thus deriving estimates of needs for care according to currently desirable standards. In a one-year study all patients 15 years or older with acute wrist trauma and treated at the emergency room were examined according to an algorithm until a diagnosis was established. The overall incidence of wrist trauma was 69 per 10,000 inhabitants per year. Incidence of wrist trauma requiring radiographic examination was 58 per 10,000 per year. The incidence of fractures of the distal radius was 27 per 10,000 per year (males, 16 per 10,000, females, 37 per 10,000 per year). In order to evaluate the completeness (defined as the proportion of patients with wrist injuries seen at the emergency room out of all patients with wrist injuries in the catchment area) of the hospital based data an analysis was performed using data from a population based study. A completeness rate of 0.56 (95% confidence interval 0.31-0.78) was found. A radiographic examination had been performed in all patients reporting a fracture, justifying the use of fractures as an incidence measure when comparing groups of patients with a wrist trauma. PMID- 8009726 TI - [Radiological findings in patients with a J-shaped ileal reservoir]. AB - This study comprised 116 patients with either ulcerative colitis or familial adenomatous polyposis, who were treated from 1983 to 1990. The patients were subjected to total colectomy followed by formation of an ileoanal reservoir (J pouch). In a retrospective study the radiological findings of the J-pouch and the reservoir related complications are presented and a description of the applied technique for pouchography is given. A total of 513 radiological investigations were performed--median two per patient (range: 1-44). All 116 patients were subjected to pouchography while 59 patients additionally underwent conventional X ray investigations, 42 patients were referred to ultrasound and ten patients to CT. Fourty-five percent of the patients presented no radiological complications at all. Patients with a normal primary pouchogram showed a significantly lower risk of long term complications related to the pouch. Pouchography was a useful method for excluding pouch pathology before restoring intestinal continuity as well as showing fistulas or cavities. In cases of leakage and especially stenosis and pouchitis pouchography was, however, less reliable. Ultrasound examination combined with CT-scan was beneficial in diagnosing abscesses. PMID- 8009727 TI - [Preventive check-ups of pregnant women in Denmark. Common ailments in pregnancy]. AB - The study was conducted in order to describe the extent and content of advice on common ailments in pregnancy given by doctor or midwife during prenatal visits and to describe the frequency of ailments in the period before the visits. The design was a nationwide cross-sectional study based on questionnaires completed by pregnant women who had seen a general practitioner (GP), midwife or hospital doctor for prenatal care. Ailments and advice in connection with one specific visit were reported. The questionnaires were completed by 517 women after a prenatal visit to their GP (92% of eligible), by 514 women after a prenatal visit to the midwife (91% of eligible), and by 203 women after a prenatal visit to a doctor in the maternity department in pregnancy week 16-18 (84% of eligible). The results showed that nausea, pollakisuria, tiredness and heartburn had been present during the period before the visit in about half the women. Between a third and a fourth of the women had been discomforted by back pain, discharge or cramps. From 15 to 58 percent had been given advice, depending on the symptom. The advice was of many different kinds. To a large extent the women wanted to talk to the health professionals about the ailments, and most often they wanted to talk to a midwife about the ailments. We conclude that common ailments of pregnancy are frequent and they should be investigated more. Nearly all pregnant women want to talk about the subject during prenatal visits. The objectives of giving advice should be clearer, and clinical studies of the effectiveness of the advice are needed. PMID- 8009728 TI - [Reported occupational diseases. A 5-year follow-up study from the county of Ribe]. AB - The present study sought to examine the health-related, work-related, social and economic consequences of occupational disorders. The survey included 503 patients and was undertaken approximately five years after the disease was notified to the Registry of Occupational Diseases (Danish Working Environment services). The response rate was 80% with women accounting for 56% of the responding group. The mean age was 39.5 years. More than half of all respondents were unskilled workers. White-collar workers and civil servants constituted 14%. Musculo skeletal disorders were the most frequently diagnosed condition. Forty percent of the occupational diseases were reported in the year in which symptoms arose, while 21% of the patients had been symptomatic for more than six years before the disease was notified. The study indicates that many patients' occupational diseases caused them significant social and medical consequences. During their often protracted illnesses, patients underwent numerous medical examinations and additionally contacted several agencies other than health care providers. Economic consequences for the patient were considerable: reduced earning capacity and expenses were only partially offset by the workers' compensation system. The impact on the health care system was also considerable: occupational disease sufferers averaged one week of hospitalization and 18 visits to a general practitioner or specialist. PMID- 8009729 TI - [Testicular cancer in an 80-year old man with a previous contralateral testicular cancer]. AB - A case of contralateral testicular cancer in an 80-year-old man 40 years after his first testicular cancer is reported. The importance of taking testis biopsies from men at risk of getting a testicular cancer is discussed, especially regarding the detection of carcinoma-in-situ. PMID- 8009730 TI - [Clinical trials of naturopathic preparations or strong preparations of vitamins and minerals]. PMID- 8009731 TI - [Connection between respiratory tract diseases during early childhood and asthma in adolescence]. PMID- 8009732 TI - [Alcohol and subdural hematomas]. PMID- 8009734 TI - [Parallel publications in the Ugeskrift]. PMID- 8009733 TI - [Fish oils and essential fatty acids]. PMID- 8009735 TI - [Renovascular hypertension]. PMID- 8009736 TI - [Surgical treatment of renovascular hypertension caused by renal artery stenosis. A retrospective study]. AB - During a 10 year period 58 patients with renovascular hypertension due to renal artery stenosis were treated surgically. A retrospective analysis of the results was carried out. No perioperative mortalities occurred. Ten percent of the patients developed hypertension again after an average of 27 months. At follow-up (median 65 months), 85% of the patients had normal blood pressure or either no, modest or considerably reduced anti-hypertensive medication. It is concluded that surgical treatment of renovascular hypertension is a safe and effective procedure. PMID- 8009737 TI - [Angiotensin-converting enzyme inhibitor renography. Physiopathological, diagnostic and therapeutic aspects in renal artery stenosis]. AB - Angiotensin converting enzyme inhibitor renography (ACE-I-renography) can be used partly to screen for renovascular hypertension and partly to evaluate the possibility for successful revascularization. In patients with an important renal artery stenosis with a high intrarenal activity of the renin-angiotensin-system ACE-inhibition results in a change in renal haemodynamics which can be detected by renography. ACE-I-renography has a high positive and negative predictive value in diagnosing renal artery stenosis. Significant alterations in the renogram induced by ACE-inhibition in renal artery stenosis seem to have a good predictive value with regard to the effect of correction of the stenosis. ACE-I-renography is recommended in patients with arterial hypertension and a moderate or high probability for renovascular hypertension based on clinical criteria. PMID- 8009739 TI - [Children's requirements for dietary calcium]. AB - Childrens' need for calcium is uncertain, and as a consequence there are large differences in the official recommendations for calcium intake. A low calcium intake is not followed by acute complications. A very low calcium intake (less than 200 mg/d) combined with a high intake of fibre and phytate can cause osteomalacia, as in rickets. Several studies support that calcium intake during growth is positively associated to bone mineralisation, and to peak bone mass, which is associated to the risk of developing osteoporosis. At present, we know very little about childrens' ability to adapt to a low calcium intake. Furthermore, knowledge of the capacity for catch-up mineralisation after a period of low calcium intake is limited. Bone mineralisation during growth is also influenced by physical activity, hormonal status and race. The relative importance of these factors is unknown. Longitudinal studies of bone mineralisation using DXA scanning will, in the future, increase our knowledge about the need for calcium during growth. PMID- 8009738 TI - [The importance of nutrition for the prevention of osteoporosis]. AB - The prevalence of osteoporosis is increasing, and is a significant burden on society. Dietary composition is an important determinant of the bone mineral density in the growth period, and of the magnitude of the age related bone mineral loss, in particular among postmenopausal women. Therefore, an improvement of the diet has an important role in the prevention of osteoporosis. A sufficient intake of calcium and vitamin D can reduce the risk of fractures in postmenopausal women, and it is likely that a low calcium intake may affect peak bone mass negatively. Calcium in the Danish diet comes mainly from dairy products. Half a litre of milk and 25 g of cheese will cover most people's calcium requirement. Part of the calcium requirement may also be covered by consuming other foods such as cabbage, broccoli and beans. Children, adolescents and elderly individuals who avoid dairy products are recommended to take a calcium supplement. The status of vitamin D among the elderly can be improved by a daily outdoor stay and by a frequent intake of fatty fish such as herrings. Elderly persons who stay indoors are recommended to take a vitamin D supplement. PMID- 8009740 TI - [Surgical treatment of diffuse peritonitis caused by perforated perisigmoiditis. A prospective, randomized study]. AB - A prospective randomized trial was carried out on 62 patients with diffuse peritonitis from perforated diverticulitis of the left colon, which compared acute transverse colostomy, suture and omental covering of a visible perforation to acute resection without primary anastomosis. For purulent peritonitis the postoperative mortality rate was significantly higher after acute resection (six of 25) than after colostomy (none of 21). In those treated by acute resection, the mortality rate was not significantly higher after Hartmann's procedure (five of 15) than after exteriorization of both lumens (one of ten). The postoperative mortality rate in patients with faecal peritonitis did not differ significantly between colostomy (six of ten) and acute resection (two of six). Stomas became permanent in four of 25 patients with diverticulitis surviving acute colostomy and in seven of 22 surviving acute resection. Suture and transverse colostomy is superior to resection for purulent peritonitis because of the lower postoperative mortality rate. PMID- 8009741 TI - [Phantom breast syndrome]. AB - Phantom breast syndrome following mastectomy has been reported by other authors. However, the temporal course, character and extent of this phenomena have not been elucidated. In a prospective study we have investigated the incidence, clinical picture and temporal course of phantom breast syndrome. One hundred and twenty women who started postoperative control or treatment at the Oncology Department over a one-year period were interviewed by a standard questionnaire three weeks after the operation. One year later 110 patients and six years later 68 patients were interviewed again. The incidence of phantom pain and non-painful phantom sensations was respectively 13.3% and 15.0%, respectively three weeks after the mastectomy. 12.7% and 11.8% after one year, and 17.4% and 11.8% after six years. A significant relationship between preoperative pain and phantom breast syndrome was found, but neither age, cancer treatment or postoperative sequelae seemed to affect the occurrence of phantom breast syndrome. Scar pain was found to persist in 30.9% of the patients six years after the operation. The present incidence of phantom-related phenomena is close to the incidence reported by others. However, persistent phantom pain after mastectomy may be more common than usually expected. Also, the persistence of scar pain seems to be more common than generally expected. PMID- 8009742 TI - [Spread of teflon particles from periurethrally injected teflon paste to pulmonary tissue]. AB - Periurethral injections of pyrolyzed teflon are used for control of urinary incontinence. Here a case is reported in which teflon-particles have spread from periurethrally injected teflon to pulmonary tissue. Teflon embolization to the lungs from artificial heart valves has previously been reported. The differences between these two forms of teflon-embolization are discussed. The risk of carcinogenicity is discussed. PMID- 8009743 TI - [Chronic hypertrophic pharyngitis]. PMID- 8009744 TI - [May genetic tests be used in prevention of occupational diseases?]. PMID- 8009745 TI - [Occupational exposure to blood among health personnel]. PMID- 8009746 TI - [Silicone and sunscreening agents]. PMID- 8009747 TI - [Validity of the registration of infections]. PMID- 8009748 TI - [Acetylsalicylic acid, a new era for an old drug?]. PMID- 8009749 TI - [Validity of a system for registration of infections]. AB - A study was undertaken to determine the sensitivity of a computerized surveillance system for postoperative wound infection. From 1987 to 1990, 5177 orthopaedic operations were recorded. Four hundred and forty-five randomly selected patients received a questionnaire. Three hundred and eighty-eight (87.2%) replied. Of 355 (79.8%) usable answers, 75 (21.1%) stated to have had signs of infection, 50 (14.1%) had been seen by a doctor, 25 (7.0%) had not found this necessary. We found seven patients with deep wound infection of which three were not recorded. The sensitivity of the surveillance system concerning deep wound infection was found to be 57.1% (18.4-90.1), and for superficial wound infection to be 9.1% (1.9-24.3). We conclude that the surveillance system is not useful for the intended purpose. We propose to record a few selected types of operation, where all should be seen as out-patients at a suitable time following operation, and thereby get a more valid recording of the frequency of postoperative wound infection. PMID- 8009750 TI - [Acetylsalicylic acid treatment after peripheral vascular surgery]. AB - Antiplatelet drugs (acetylsalicylic acid) have been widely used in arteriosclerotic patients during recent years. We have reviewed the literature to find out if this treatment also is indicated in patients operated with reconstructive vascular surgery for lower limb ischemia. It is concluded, that all patients should receive life-long treatment with acetylsalicylic acid 300-500 mg per day following peripheral vascular surgery. This will improve the patency rate of certain vascular procedures, and in all patients it reduces the incidence of cerebral stroke and the risk of myocardial infarction in the years following peripheral vascular surgery. PMID- 8009751 TI - [Preoperative EEG in medically intractable epilepsy]. AB - The aim of the preoperative neurophysiological investigations is to identify the primary epileptogenic focus and its relation to functional cortical areas. The investigations include interictal and ictal extracranial (scalp) electroencephalography (EEG) and invasive methods (depth, subdural, foramen ovale electrodes and peroperative electrocorticography). If an epileptic focus is located in the anterior part of the temporal lobe by the use of scalp EEG, this is normally regarded as sufficient for an anterior lobectomy. However, because of poor spatial resolution by scalp EEG, it is difficult to separate mesial from lateral foci, identify the exact extent of posterior temporal or extra-temporal foci, identify the primary focus in patients with bilateral abnormalities and identify cases with minor scalp EEG-changes. As invasive EEG shows higher spatial resolution and gives an opportunity to evaluate functional areas, invasive EEG has significant advantages in these patients. Use of invasive EEG bears a slightly increased risk and discomfort to the patient, but is necessary in the presurgical evaluation of some patients suffering from medically intractable epilepsy. PMID- 8009752 TI - [Controlled alcohol intake. Is it possible to predict which alcohol abusers can manage a more controlled drinking?]. AB - The purpose of this investigation was to identify parameters of predictive value as to which alcohol abusers can manage controlled alcohol intake. Of 72 patients admitted during one year with alcohol abuse as a major diagnosis 27 attempted controlled drinking in a total of 64 events. Socio-demographic data and history of alcohol abuse had no predictive value in identifying patients who could achieve a controlled alcohol intake. However, it appears that a desire and hope for an improved psychological well-being can increase alcohol-abusers' control of alcohol intake. We also found a good correlation between the opinion of an experienced clinician as to which patients should attempt controlled drinking and the patients' own estimation of their possibilities, but neither evaluation had predictive value for the outcome of attempts at drinking. We conclude that it is difficult to predict the outcome of attempted controlled alcohol intake during and after treatment for alcohol abuse. PMID- 8009753 TI - [Alcohol intake, Lewis phenotypes and risk of ischemic heart disease. The Copenhagen Male Study]. AB - In the Copenhagen Male Study we found an increased risk of ischaemic heart disease (IHD) in men with the Lewis phenotype Le(a-b-). This study investigated whether, within the group of Le(a-b-) men, any conventional risk factors modified their increased risk. Three thousand, three hundred and eighty-three men aged 53 to 75 years were examined in 1985/86 and their morbidity and mortality over the next four years recorded. Three hundred and forty-three men with cardiovascular diseases were excluded at baseline. Potential risk factors examined were: alcohol consumption, physical activity, tobacco smoking, serum cotinine, serum lipids, body mass index, blood pressure, hypertension, non-insulin dependent diabetes mellitus and social class. In eligible men with Le(a-b-), N = 280 (9.6%), alcohol was the only risk factor associated with risk of IHD. There was a significant inverse dose-effect relationship between alcohol consumption and risk. The age adjusted p-values of trend tests were for risk of non-fatal + fatal IHD: p = 0.03; for risk of fatal IHD: p = 0.02. In eligible men with other phenotypes, N = 2,649 (90.4%) only a limited and non-significant negative association with alcohol. In Le(a-b-) men, a group genetically at increased risk of IHD, the risk was strongly and significantly negatively correlated with alcohol consumption. PMID- 8009754 TI - [Fish oil supplementation and duration of pregnancy. A randomized controlled trial]. AB - It was hypothesised from previous observational studies in the Faroes and Denmark that dietary marine n-3 fatty acids would prolong the duration of pregnancy and thereby increase the birth weight, by influencing the production of prostaglandins involved in the process of parturition. Five hundred and thirty three healthy Danish women were randomly assigned in the 30th week of pregnancy to fish oil (2.7 g n-3 fatty acids (4 1-g capsules Pikasol oil) per day), olive oil (4 1-g capsules per day) or no oil supplementation. The three groups differed in mean gestational age at birth (ANOVA, p = 0.006), with the fish oil group ranking highest and the olive oil group lowest. Babies born to women allocated fish oil had on average 4.0 (95% confidence interval 1.5;6.4) days higher gestational age and 107 (95% confidence interval 1;214) g higher weight at birth than babies born to women allocated olive oil; the difference in gestational age depended on the level of fish intake at enrollment, with a low fish intake enhancing the difference. Fish oil supplementation in the third trimester seems to prolong gestation while allowing continued growth of the foetus; this effect seems to explain the difference between the Faroes and Denmark in pregnancy duration. PMID- 8009755 TI - [Appendicitis in pregnancy. Complications and treatment]. AB - In order to establish guidelines for the management of a pregnancy that is complicated by acute appendicitis we carried out a retrospective review of 16 patients that had their appendix removed at the Department of Obstetrics and Gynaecology, Rigshospitalet, University of Copenhagen in the period 1974-1988. The diagnostic accuracy was 12/16 (75%). The signs and symptoms were classic. Uterine contractions may occur. There was one foetal death in a case complicated by an intraperitoneal abscess, and two patients delivered prematurely. Three patients had infectious complications, none of these patients were given prophylactic antibiotics. In all uncomplicated cases the pregnancy proceeded to term and the deliveries were normal. The pregnancy ought not to divert the surgeon's attention from performing prompt appendectomy once the diagnosis is suspected. Prophylactic antibiotics and tocolytic drugs should be used in all cases. Simultaneous caesarean section should be performed only on obstetric indications. PMID- 8009756 TI - [AIDS with apoplectic onset]. AB - Four cases with an apoplectic debut of AIDS are reported. Two of the patients had not earlier been identified as being HIV-positive. In three patients, the underlying cause was probably cerebral toxoplasmosis. It is important to consider AIDS in the differential diagnosis of stroke, particularly in young adults. PMID- 8009757 TI - [Heart patients and uncritical cholesterol-inhibiting therapy using statins]. PMID- 8009758 TI - [T/QRS ratio and cardiotocographic changes in the second stage of labor]. PMID- 8009759 TI - [Loperamide and childhood diarrhea]. PMID- 8009761 TI - [AIDS-risk and blood transfusion]. PMID- 8009760 TI - [Are women better in practicing safe sex?]. PMID- 8009762 TI - [Staged investigation of vestibular function]. AB - The needs in vestibular function investigation for definite diagnosis, occupational selection, expertize, emergency care in field conditions have been increasing of late. Most accurate and informative evidence can now be obtained only in large specialized clinics practicing updated quantitative techniques. The authors propose a scheme for staged investigation of vestibular function contributing to early diagnosis of labyrinthine and retrolabyrinthine disturbances: stage I--outpatient examination in the ENT department of a district outpatient clinic; stage II--regular aid--surdological or ENT consultation, the diagnostic center; stage III--expert care--ENT clinics or research centers. Minimal tests and examinations at each of the three stages are specified. PMID- 8009763 TI - [Current methods in the investigation of nasal respiratory function as an alternative to rhinomanometry]. PMID- 8009765 TI - [Improvement of hearing acuity using ergomyogenic blood autoserum]. AB - Biological activity of ergomyogenic autoserum (EAS) is attributed to the presence of natural hormonal-neuropeptide complex. Its administration to 25 healthy volunteers and 20 patients with neurosensory hypoacusis stage I-II resulted in improvement of hearing acuity in all the subjects with normal hearing and in 75% of the patients. The autoserum usage instructions are provided. PMID- 8009764 TI - [Some immunologic indices in patients with chronic polypous rhinosinusitis]. AB - Such immunological indices as the number of T- and B-cells in a rosette-formation test, T-cell sensitivity to theophylline, quantity of the main Ig classes and CIC were investigated in 43 patients with primary chronic polypous rhinosinusitis and 34 patients with recurrent polypous rhinosinusitis. Elevated levels were registered of IgG, IgM, IgA and CIC this evidencing hyperfunction of B-cell immunity. Immunocorrection with sodium nucleinate in surgical treatment of sinusitides contributed to more rapid recovery of the patients. PMID- 8009766 TI - [Some structural characteristics of articulation of the incus and stapes in man]. AB - Structural characteristics of human incudostapedial articulation (ISA) have been studied on a series of histological sections from temporal bone decalcified pyramids in three planes and by means of macro-micropreparation of tympanal structural elements from 96 human fetuses at various terms of gestation. It was established that the surface of the lenticular process has a spherical form. Its length surpasses its width. The articular surface on the head of the stapes presents a dome-shaped lacuna. The capsule is usually thicker in its posterior part than in the anterior one. It can endure deviation of the long lenticular process up to 3 mm without rupture. When the deviation overruns 3.5 mm, the articular bursa and round ligament of the base of the stapes break. This property of the capsule should be kept in mind when operating on the stapes. PMID- 8009767 TI - [Use of steam-oxygen tents with a universal steam generator and automatic control system in the treatment of acute stenosing laryngotracheitis in children]. AB - To treat acute stenosing laryngotracheitis in acute respiratory viral infection in children an original method has been developed and used for 2 years in a special hospital department. The method implies treatment of children in steam and-oxygen tents with a universal steam-moistening generator and automatic control system. A controlled study of 50 children with acute laryngeal stenosis degree I-III confirmed high efficacy of this method permitting improvement of blood oxygenation, gas composition, acid-base condition, reduction of acidosis, prevention of exicosis and brain edema. Warm humid atmosphere promoted better discharge of the secretion and better functioning of the ciliated epithelium. Combined treatment incorporating the tents in acute laryngeal stenoses reduced lethality in severe cases, number of intubations and tracheostomies, of complications resultant from parenteral administration of the drugs. PMID- 8009768 TI - [Contact laser microsurgery in laryngeal neoplasms]. AB - Basing on the results obtained in 129 patients with benign and 135 ones with malignant laryngeal tumors the author provides theoretical and practical grounds for introduction of high-energy YAG laser under contact regimen in endolaryngeal microsurgery of relevant tumors. Advantages of the method, indications and contraindications to its application are considered in detail. PMID- 8009769 TI - [Experience with radical resection of the larynx in stage III - IV cancer]. AB - Laryngectomy has been performed as first-line treatment in 23 patients with laryngeal cancer stage III-IV. The author has modified the final stage of the surgery: laryngeal defect suturing with a continuous suture and the wound drainage. Two patients were operated on radically. Five-year follow-up covered 3, 3-year one 15 patients. None of them had recurrence or metastases. Healing by first intention was observed in 74% of the patients. It is inferred that laryngectomy is effective as an initial stage of combined treatment of laryngeal cancer stage III-IV. The modification of the surgery final stage reduces the frequency of postoperative complications in the absence of inflammation in the tissues adjacent to tracheostoma. PMID- 8009770 TI - [A method of organ-preserving tonsillotomy]. AB - An original method of conservative tonsillotomy proposed for surgical treatment of hypertrophic tonsils in preschool children preserves anatomical structures of the tonsils and relevant physiological functions, reduces duration of treatment, prevents chronic inflammation in the tonsillar tissues. The operation implies removal of small hypertrophic parts of the tonsil primarily in the lower pole. The operation is performed under anesthesia with tracheal intubation and employment of Bochon loop. PMID- 8009771 TI - [Characteristics of the course and treatment of inflammatory nasal and paranasal sinus diseases in pregnancy]. AB - The authors report quantitative and qualitative characteristics of nasal and paranasal diseases in 139 pregnant women. Acute purulent maxillary sinusitis was associated with relative T-cell immunodeficiency with unbalance of the regulatory cells. It is concluded that treatment of the above conditions in pregnancy should be conducted without damage to the fetus and include immunocorrection. PMID- 8009772 TI - [Use of MK-2 glue and short-term cotton tamponade in submucous resection of the nasal septum]. AB - Clinical responses were compared in use of conventional gauze anterior tamponada, bioglue and short-term (5-8 hr) cotton tamponada employed in submucous resection of the nasal septum. Fixation of the septal laminae according to the above method provided more relief to postoperative patients, reduced their stay in hospital up to 1 day and temporary disability two-fold making outpatient resection of the nasal septum more practicable. PMID- 8009773 TI - [Dimethyl sulfoxide in the treatment of patients with inflammatory diseases of external and middle ear]. AB - The combination of various drugs with midethyl sulfoxide (DS) solution has been tried in 49 patients with inflammation of the external ear and 10 patients with acute otitis media. It was found that DS solutions potentiate the effect of the drugs. A broad antibacterial and antimycotic spectrum, high transdermal, analgetic, antiinflammatory and potentiating potential in good side-effect profile made it possible to recommend DS for management of external and middle ear inflammation. PMID- 8009774 TI - [Bioceramic prosthesis of the ear ossicles in tympanoplasty]. AB - Anvil bones bioceramic prostheses were used in tympanoplasty performed in 60 patients with chronic otitis media purulenta (COMP). Complete and partial variants of the prostheses were tried. Follow-up results available for 60 patients demonstrate that the above tympanoplasty improved hearing in 41 out of 60 patients, made possible complete cavity epidermization, arrested inflammation, secured safety of the tympanic transplant in 51 patients. Bioceramic prostheses of the anvil bones provide stable hearing improvement even in COMP cases with severe impairment of the anvil bones. PMID- 8009776 TI - [Organizational model for realistic planning of ambulatory/ outpatient otorhinolaryngology care to the population of a region]. AB - A model of planning a real scope of ENT service in the region has been developed basing on the material of a rural regional hospital. PMID- 8009775 TI - [Changes of periods in caloric nystagmus in pathology and their physiologic interpretation]. PMID- 8009777 TI - [Proceedings of the 19th meeting of the Moscow Scientific and Practice Association of Otorhinolaryngologists , November 13, 1990]. PMID- 8009778 TI - [Physiologic validation of the method of functional hearing tests for evaluation of hearing function]. AB - Physiological validation is presented for application of ototopicometry. This method is intended for measurements of minimal recognizable angles of a moving sound object localization in several space planes. Quantitative characteristics of ototopical function in healthy subjects upon localization of various sound stimuli are described. Ototopicometry is proposed as an additional audiological test for functional assessment of the acoustic human system. PMID- 8009779 TI - [Labor induction in cows and its effect on the development of biochemical and hematologic indicators in the blood of calves]. AB - The effect of induction of parturitions in the 1-2 weeks of pregnancy was tested as exerted on the health of calves and on some biochemical and hematological indicators. The observations concerned 26 cows, out of which 14 cows (experimental group) were applied intramuscularly 500 micrograms of synthetic analog of prostaglandin F2 of alpha- cloprostenol. The other 12 cows were a control group. These indicators were determined in the blood of calves before colostrum intake, in 24 h, 5 and 15 days from the intake of the first colostrum ration: acid-base balance, hematocrit and leucocyte counts, in the blood plasma it was concentrations of glucose, urea, Na, K, Ca, inorganic P, vitamin A and E levels and AST and GMT activities. The same range of examinations was performed in the blood and/or in the blood plasma of cows, in addition to urea screening. Blood and urea samples were taken a month before and a month after parturition. No deviations from the normal state were found by the examination of highly pregnant cows. Afterbirth retention was found in 87% cows of the experimental group after parturition, while it was only 9.8% in the control group. All the calves in the experiment had good vitality, very good health in the course of 15 day observation. There were not any significant differences in the birth weight and weight gains of the calves of experimental and control groups.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8009780 TI - [Preclinical diagnosis of metabolic osteopathy in feedlot bulls]. AB - Diagnostic significance of some clinico-biochemical parameters was investigated in 221 fattened bulls. An evaluation of the results has shown that the determination of concentrations of calcium, inorganic phosphorus and alkaline phosphatase activity in blood plasma was not of essential importance for diagnostics. The values of these parameters were within the reference range (Tab. I). The parameters determined by chemical analyses of bioptates from the tuber coxae of the fattened bulls with various forms of alimentary osteopathy showed characteristics, statistically significant differences in comparison with the control animals (Tabs. II, III, IV). In the bulls of group B/1 (clinically healthy, phosphorus deficit in the feed ration, acidogenic nutrition in part of the animals, lowered performance, occurrence of clinical cases of osteopathy in fattening facilities), a significant decrease in the values of ash per 1 g fat free dry matter and per 1 cm3 spongy substance of the t. coxae and a significantly wider index Ca/P were determined. In the bulls of group B/2 (clinically healthy, deficit of phosphorus, calcium, proteins and energy in the feed ration, decreased performance, occurrence of clinical osteopathy), a significant decrease of ash per 1 g fat-free dry matter and per 1 cm3 of spongy substance of the t. coxae was determined, the Ca/P index was significantly narrower. In the bulls of group C/1 (bulls with clinical symptoms of skeleton disorder, phosphorus deficit in the feed ration, acidogenic nutrition in part of the animals), a significant decrease of ash per 1 g far-free dry matter and per 1 cm3 spongy substance of the t. coxae was found out, the Ca/P index was wider.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8009781 TI - [Transfer of amino acids across the rumen epithelium in sheep: interaction between leucine and lysine]. AB - Experiments were conducted on six head of sheep of the Slovak Merino breed with average live weight of 40 kg. The sheep received 0.4 kg of industrially produced molasses feed M and 1 kg of meadow hay once a day. The feed ration for a head of sheep per day contained: 1177.58 g dry matter, 89 g digestible crude protein (SNL), 0.554 starch units. The animals had free choice of water. Rumen epithelium with submucosa was used in the experiment. Amino acid transfer was measured in a mucosa-serosa direction. Amino acids were dissolved in Thyrode's solution with pH value 6.9 on the mucosa side and 7.4 on the serosa side. A constant temperature of 39 degrees C was maintained during the experiment. The epithelium area was 13.2 cm2 for either part of the experiment. Lysine and leucine were incubated separately in the first part of experiment. These concentrations were used: 5, 25, 50 and 75 mumol/l. The values of lysine and leucine readings are denoted as control lysine (lysine K) and control leucine (leucine K) in the result section. Lysine and leucine were incubated simultaneously in the second part of experiment: Lys 5 mumol/l-Leu 5 mumol/l; Lys 5 mumol/l--Leu 15 mumol/l; Lys 5 mumol/l--Leu 20 mumol/l; Lys 25 mumol/l--Leu 25 mumol/l; Lys 25 mumol/l--Leu 75 mumol/l. The values of lysine readings on the other part of experiment are denoted as experimental lysine (lysine P). Figs. 1 and 2 show transfer of control lysine and leucine through the rumen epithelium as depending upon their concentrations.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8009783 TI - [Epizootiology and pathogenesis of avian mycobacteriosis in the laughing gull (Larus ridibundus)]. AB - The occurrence of avian mycobacteriosis and sensitivity to M. avium were investigated in the laughing gull in this paper. The patho-morphological and culture examination of 35 individuals of the laughing gull caught at four different localities of the Czech Republic did not reveal any tuberculous lesions nor did it enable to isolate mycobacteria. After experimental intramuscular infection by suspension of M. avium macroscopic tuberculous lesions were found at the spot of puncture in 35 days, in liver and spleen in 70 days since the beginning of infection. In the simultaneously infected domestic fowl the lesions were determined at the spot of puncture, in spleen and liver in 35 days. Mycobacteria were isolated from several organs and tissues in both species in 35 days after infection. Tuberculous lesions were found in liver, spleen and intestines of the laughing gull in 118 days since peroral infection by feed contaminated with the liver of tuberculous fowl. This finding was identical in spleen of the domestic fowl only in 118 days. Mycobacteria were demonstrated in both species in 118 days, in liver, spleen, intestine and/or brain in the laughing gull, while in spleen only in the domestic fowl. Intestinal tuberculosis was determined in the laughing gull in 118 days after infection. The results of experimental infections show that the sensitivity of the laughing gull to M. avium is the same as in the domestic fowl. The occurrence of tuberculosis in the laughing gull is apparently depending upon the local epizootological situation, particularly upon the occurrence of M. avium sources and their accessibility.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8009784 TI - [First cases of verified spontaneous infection of cattle by Cryptosporidium muris Tyzzer (1907), 1910 in the Czech Republic]. PMID- 8009782 TI - [Polymorphism of alphas-casein in white short-haired polled goats]. AB - Distribution of alleles of the alphas-casein complex was studied by isoelectric focusing in the White Shorthaired Polled goat according to the method of Krause et al. (1988) and Mahe et al. (1993). In addition to the common alleles alpha s1 CnA and B, the alpha s1-CnE allele is described; it has not yet been observed in this breed. We are not able to confirm the occurrence of the alpha s1-CnC allele. At least one out of three defective mutants (alpha s1-CnD,F and 0) was found, nevertheless their identification was not discussed. The following percentile occurrence (Tab. I) of the above-mentioned alleles of alpha s1-casein was determined: alpha s1-CnA = 11.30; alpha s1-CnB = 38.26; alpha s1-CnC = 0; alpha s1-CnE = 17.39; alpha s1-CnX = 33.04 (the letter X indicates the defective mutants without specifying their type and number). Our results differ significantly from those of Boulamger et al. (1984), Grosclaude et al. (1987) and Trakovicka (1992). Higher (in contrast to the French authors) and lower alpha s1 casein allele rates (as compared to Trakovicka, 1992) were observed. The higher occurrence of the alpha s2-CnB is also conspicuous. However, our observations correspond to those according to which the "strong" alleles have higher frequencies in European breeds than in the French ones (Grosclaude et al., 1992 cit. Mahe et al., 1993). The alleles of alpha s2-casein were also investigated. The electrophoretic variant of the alpha s2-casein was observed next to the type B and located closer to the anode (suspected mutation); on that account it was named B-. This variant was also seen in a homozygous form.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8009785 TI - Bovine immunodeficiency-like virus--a potential cause of disease in cattle? PMID- 8009786 TI - Parapox infection in grey seals (Halichoerus grypus) in Cornwall. AB - In the winter of 1991/92 there was an outbreak of parapox infection in grey seals (Halichoerus grypus) around the coast of Cornwall. Pups were cared for at a seal rehabilitation centre and the infection occurred in most of them. The presence of parapox virus was confirmed by electron microscopy. The clinical and pathological findings, together with details of the morphology of the virus, are compared with those in previous outbreaks in North America. PMID- 8009787 TI - Necrotic enteritis of unknown aetiology in young beef calves at pasture. AB - An enteric disease has occurred for four consecutive years (1989 to 1992) in a spring-calving beef suckler herd in east central Scotland affecting seven- to 12 week-old beef calves. The affected animals remained pyrexic (40 to 42 degrees C) with an acute enteritis which progressed in some cases to severe mucohaemorrhagic colitis. Despite intensive antibiotic and fluid therapy 25 per cent of the affected calves died after five to 10 days of illness. Post mortem examination revealed ulceration and necrosis of the mucosa of the abomasum and small and large intestine. Haematological examinations revealed a severe, non-regenerative neutropenia. Histopathological examination of gut and associated lymphoid tissue revealed lesions similar to those described in bovine viral diarrhoea/mucosal disease (BVD/MD) infection but detailed investigations failed to reveal evidence of active BVD virus infection in the herd. No aetiological agent has been found in association with this disease, for which the term necrotic enteritis is proposed. PMID- 8009788 TI - Rapid differential diagnosis of rinderpest and peste des petits ruminants using an immunocapture ELISA. AB - An immunocapture ELISA for the diagnosis of rinderpest and peste des petits ruminants is described. Monoclonal antibodies directed against non-overlapping antigenic domains on the nucleocapsid (N) were used to detect the virus N protein in supernatants from infected cells and in field specimens. The assay, which is very sensitive, can be performed in one hour on pre-coated plates. There was no cross reaction between the two viruses in the test and the N protein could be detected in infected cell supernatants kept at ambient temperature for one week. These results show that the ELISA is suitable for routine diagnosis of field samples. PMID- 8009789 TI - Non-transmission of porcine reproductive and respiratory syndrome virus by seropositive pigs from an infected herd. PMID- 8009790 TI - Orthopaedic injuries in pigeons. PMID- 8009791 TI - Problems in a Cheshire herd. PMID- 8009792 TI - Vaccination and fibrosarcomas in cats. PMID- 8009793 TI - Multicentric liposarcoma in a cow. PMID- 8009794 TI - Dermatitis/nephropathy syndrome in pigs. PMID- 8009795 TI - Examinations in veterinary pathology. PMID- 8009796 TI - Check chains. PMID- 8009797 TI - Fluorescent tubes. PMID- 8009798 TI - Clinical aspects of Chlamydia psittaci infection in cats infected with feline immunodeficiency virus. AB - Two groups of six cats were established, one a control group and one infected with feline immunodeficiency virus (FIV) 18 months previously. The cats in both groups were inoculated with Chlamydia psittaci and the clinical progression of the infection was monitored by means of a clinical scoring system for 10 months. Haematological, serological and viral and chlamydial isolation studies were also made. The response of the FIV infected group to treatment with oxytetracycline was monitored in the 11th and 12th months. The FIV infection prolonged the duration of the clinical signs resulting from the infection with C psittaci and led to the development of chronic conjunctivitis. The haematological and antibody responses to C psittaci were comparable in the two groups. However, it was possible to isolate C psittaci from the FIV-infected cats up to day 270, when the treatment began, but only up to day 70 in the control group. In addition, it appeared that the infection with a secondary pathogen may have accelerated the clinical progression of the FIV infection. PMID- 8009799 TI - Canine Lyme disease: clinical and serological evaluations in 21 dogs in Japan. AB - Of 21 dogs from Sapporo, Hokkaido that had been recognised as having been bitten by ticks, 16 were seropositive to Borrelia burgdorferi by ELISA. Thirteen of the seropositive dogs showed signs such as fever, astasia, convulsions, anorexia, fatigue, abnormal gait, nervous signs, diarrhoea, corneal opacity and conjunctivitis. These signs subsided as a result of antibiotic treatment within five days. The plasma concentrations of creatinine in the 21 dogs were higher than in control dogs. Seven ticks that were removed from seven of the dogs were Ixodes persulcatus, and B burgdorferi was isolated from the midgut of two of the ticks. PMID- 8009800 TI - A study of obese cats on a calorie-controlled weight reduction programme. AB - Twenty-two domestic cats were fed a commercial low calorie diet for the management of obesity for up to 18 weeks and showed an average weight loss of 13.5 per cent of their body-weight. There was no indication that a steady weight loss over the study period had any adverse effect on the hepatic function or general health of the cats. There was an increase in the cats' total serum cholesterol concentration in association with the loss of weight. PMID- 8009801 TI - Progressive retinal atrophy in the Tibetan spaniel in Norway and Sweden. AB - Progressive retinal atrophy of the late onset type was diagnosed in 51 Tibetan spaniels in Norway and Sweden. At the time of diagnosis they were between three and seven years old; however, early ophthalmoscopic changes caused by the thinning of the retina could sometimes be difficult to observe because of the partial or total lack of the tapetum in many of the dogs. The disease developed rapidly, approximately one year passing from the initial clinical signs of night blindness to complete loss of vision. Twenty-four male and 27 female dogs were affected. All the affected dogs were interrelated and could be traced back to common English ancestors. On the basis of pedigree studies, an autosomal recessive mode of inheritance is postulated. Information on 15 diagnosed cases of the condition in other countries shows that the disease may be considered a worldwide problem in the Tibetan spaniel. PMID- 8009802 TI - Lipid content of cerumen from normal dogs and otitic canine ears. PMID- 8009803 TI - Absence of antinuclear antibodies in dogs infected with Ehrlichia canis. PMID- 8009804 TI - Avulsion of the lateral head of the gastrocnemius muscle in a working dog. PMID- 8009805 TI - Photosynthesis of vitamin D3 in cats. PMID- 8009806 TI - Fluorescent tubes. PMID- 8009807 TI - Tuberculosis in cats. PMID- 8009808 TI - Tuberculosis in cats. PMID- 8009809 TI - Coprophagic complications. PMID- 8009810 TI - Effects of flurbiprofen on recombinant human IL-1 alpha-induced fever and associated clinical, haematological and blood biochemical changes in the dwarf goat. AB - Flurbiprofen, a potent NSAID, was given as an intravenous infusion (1 mg/kg) to dwarf goats. After drug administration, no significant changes were observed in heart rate and rumen motility, whereas rectal temperature increased slightly; mean plasma glucose and creatinine concentrations gradually increased during the observation period. Plasma iron concentration and the number of circulating lymphocytes were significantly lower after flurbiprofen infusion. Intravenous injection of recombinant human interleukin-1 alpha (r. HuIL-1 alpha: 0.5 microgram/kg) caused shivering, fever, inhibition of rumen contractions, tachycardia, hypoferraemia, hypozincaemia, hyperglycaemia followed by hypoglycaemia, changes in plasma urea and creatinine values, lymphopaenia and neutropaenia followed by neutrophilic leukocytosis. Pretreatment with flurbiprofen partly antagonized the febrile reactions to r.HuIL-1 alpha. The r.HuIL-1 alpha-induced tachycardia and inhibition of rumen contractions were only delayed. The drug prevented the initial hyperglycaemia but did not abolish the secondary hypoglycaemia. Furthermore, flurbiprofen delayed the decline in plasma zinc and iron concentrations, whereas plasma creatinine values were significantly lower. Finally, after drug pretreatment the changes in circulating neutrophils were more pronounced. These data demonstrate that most of the haematological, blood biochemical, and clinical effects of r.HuIL-1 alpha cannot be blocked by flurbiprofen, suggesting that an increased synthesis of prostaglandins is not involved in these r.HuIL-1 alpha-induced effects. PMID- 8009811 TI - Serotyping and quantitative determination of in vitro antibiotic susceptibility of Actinobacillus pleuropneumoniae strains isolated in Belgium (July 1991-August 1992). AB - One hundred and ninety nine Actinobacillus pleuropneumoniae isolates obtained from the respiratory tract of pigs in Belgium (1991-1992) were serotyped using slide agglutination and slide precipitation tests. Biotype 1-serotype 2 and 3 strains were isolated most frequently and represented 36% and 21% of the isolates, respectively. Serotype 9 and serotype 5B strains represented 15% and 10% of the total number of isolates, respectively, while serotypes 7, 8, 10 and 11 were isolated only sporadically. Serotypes 5B, 10 and 11 were isolated for the first time in Belgium. Biotype 2 strains represented 12.5% of the total number and all belonged to the serotype 2. The in vitro susceptibility of 138 strains was determined for ten commonly used antibiotics. For three antibiotics, ampicillin, chloramphenicol, and oxytetracycline, a bimodal distribution of strain sensitivities was observed. A total of 17 strains (12%) were considered to have acquired resistance to one or more of these antibiotics. PMID- 8009812 TI - Alpha 1-acid glycoprotein-binding as a factor in age-related changes in the pharmacokinetics of trimethoprim in piglets. AB - This study examined the effects of plasma alpha 1-acid glycoprotein (AGP) on the protein binding and pharmacokinetics of trimethoprim (TMP) in piglets. The piglets were given 5 mg/kg of TMP intravenously at 1, 14 and 28 days after birth. The plasma AGP level was highest at day 1. Fourteen days after birth, the level decreased by about 90% of that at day 1. The level at 28 days was almost the same as that at 14 days. Plasma protein bindings of TMP depended on the AGP level but not on the albumin level. The percentage of plasma protein binding decreased from 85 to 45%, and the AGP level also decreased from 6,000 to 700 micrograms/ml. The altered protein binding of TMP affected pharmacokinetic parameters such as total body clearance (CLtot), distribution volume and therefore the elimination rate constant. These parameters correlated well with the percentage binding to plasma proteins. Maturational development in the capacity to eliminate TMP was also indicated by the increase in total body clearance of unbound drug (CLtotub), which directly reflects the elimination capacity of the body. However, its contribution to the increase in CLtot was considered not to be large. CLtotub increased twofold 14 days after birth, whereas CLtot increased about ninefold. The increase in CLtot therefore, may result from both the maturational development in elimination capacity and the AGP-dependent decrease in plasma protein binding. It is concluded that the decrease in plasma AGP level observed in piglets is one of major factors affecting the pharmacokinetics of TMP. PMID- 8009813 TI - Evaluation of a method for colour classification of veal. AB - In the Netherlands veal carcasses are classified according to colour with the aid of a colour scale. The colour scale, existing of five coloured chips, and the results of its application in the classification system were evaluated both theoretically and practically. The result was that theoretically 75% of the samples were assigned to the same and 25% to a different colour class when assessed by two people. In practice the standardized colour classification of veal in the Netherlands is carried out 45 min post mortem by an independent organization, the 'Centraal Bureau voor Slachtveediensten' (CBS). The correlation coefficient of the results of parallel classifications of 12,659 carcasses between CBS employees and inspectors was 0.88. The CBS employees assigned 80.1% of the carcasses to the same colour class, 10.5% to a colour that was one class lighter and 9.4% to a colour that was one class darker than the inspectors did. It is concluded that high reproducibility and comparability can be achieved uniform implementation of a visual colour classification system. PMID- 8009814 TI - Concentrations of serum amyloid-A (SAA) and haptoglobin (HP) as parameters of inflammatory diseases in cattle. AB - The concentrations of the acute-phase proteins, serum amyloid-A (SAA) and haptoglobin (Hp), were determined in the plasma of healthy cows (n = 25) and cows with spontaneous acute (n = 6), subacute (n = 37), or chronic (n = 7) inflammatory diseases. The plasma concentration of SAA alone, Hp alone, and the Hp/SAA ratio, differed significantly (p < 0.001) between healthy animals and animals with inflammatory diseases. Plasma Hp concentrations in the group of cows with acute inflammatory diseases were significantly (p < 0.01) different from those in the group with chronic inflammatory diseases. Moreover, the Hp/SAA ratio in chronic inflammatory diseases was significantly different from this ratio in acute (p < 0.01) and subacute (p < 0.05) inflammatory diseases. It is therefore concluded that the plasma concentrations of SAA and Hp and the Hp/SAA ratio are useful parameters to distinguish healthy animals from animals with inflammation and can be helpful in distinguishing between acute and chronic of inflammatory diseases. PMID- 8009815 TI - Bovine leukocyte adhesion deficiency--clinical course and laboratory findings in eight affected animals. AB - The clinical course of Bovine Leukocyte Adhesion Deficiency (BLAD) in eight Holstein Friesian cattle is described. Affected animals were presented with a history of poor thriving and recurrent bacterial infections. Five of these animals had to be killed because of severe respiratory disease shortly after admittance. Three affected animals survived calfhood only as a result of frequent antibacterial treatments. At one year of age, failure to thrive and stunted growth were still evident, but infections requiring antibiotic treatments occurred only sporadically. Clinical manifestations of BLAD were found in the digestive system (gingivitis, periodontitis, alveolar periostitis, diarrhoea), the respiratory system and the skin (impaired wound healing, chronic dermatitis). A leukocytosis based on a mature neutrophilia, which persisted during infection free periods, was observed in all animals. Granulocytes were substantially deficient of beta 2-integrin expression on their membranes. Anaemia, which was noted in four animals, may be related to the Anaemia of Inflammatory Disease Complex (AID). The serum total protein content increased with time and was associated with elevated gamma-globulin levels. We suggest that, at a certain age, animals affected with BLAD are able to cope with environmental agents due to compensatory mechanisms of the immune system. PMID- 8009816 TI - Oral bioavailability of sulphamethoxydiazine, sulphathiazole and sulphamoxole in dwarf goats. AB - To get a better insight into the oral bioavailability of sulphonamides in ruminants, sulphamethoxydiazine (pKa 7.0), sulphathiazole (pKa 7.2), and sulphamoxole (pKa 7.4) were administered to dwarf goats (n = 5). The drugs were given at 2-week intervals by the intravenous or intraruminal route at a dose of 100 mg per kg body weight. After IV injection, the mean half-life (t1/2 beta in h +/- SEM) was 0.80 +/- 0.10 h, 2.35 +/- 0.38 h, and 3.36 +/- 1.25 h, for sulphathiazole, sulphamoxole, and sulphamethoxydiazine, respectively and the mean distribution volume (Vd beta) was 0.23 +/- 0.05 l/kg, 0.23 +/- 0.04 l/kg, and 0.33 +/- 0.02 l/kg. After intraruminal administration, the mean bioavailability varied from 86.0 +/- 11.8% for sulphamethoxydiazine to 46.6 +/- 4.3% for sulphamoxole, and 52.6 +/- 7.2% for sulphathiazole. The elimination half-life was significantly prolonged, probably due to a low rate of drug absorption from the gastrointestinal tract. In contrast to chloramphenicol, the sulphonamides studied were stable when incubated in rumen fluid at 39 degrees C. PMID- 8009817 TI - Chlamydia psittaci infections in birds: a review on the pathogenesis and histopathological features. AB - In this review the literature on the pathogenesis and histopathological features of Chlamydia psittaci infections in birds and their significance for psittacosis/ornithosis in humans is summarized. Models of experimental infections to elucidate the pathogenicity of avian strains are discussed briefly. PMID- 8009818 TI - Ultrasonography of the uterus of the goat. AB - The use of a transabdominal or a transrectal scanning technique to visualize the uterus in goats is discussed. The results of sonographic imaging of normal (non pregnant, pregnant, postpartum) and abnormal (endometritis, hydrometra, fetal death) uterine structures are reviewed. In the goat, special attention must be paid to distinguishing between the sonographic image of hydrometra and early pregnancy. A case of hydrometra that developed in the presence of three dead fetuses is reported. It is concluded that, under field conditions, transabdominal scanning of goats, performed between days 40 and 70 after mating, yields information about pregnancy, fetal viability, and single or multiple pregnancy, while at the same time making possible a reliable differential diagnosis of pregnancy and hydrometra. PMID- 8009819 TI - Role of the neutrophil leucocyte in the local and systemic reactions during experimentally induced E. coli mastitis in cows immediately after calving. AB - Mammary leucocytes are the major contributors to natural defence against mastitis after a microorganism has entered the gland. This paper reviews the role of the neutrophil granulocyte during acute coliform mastitis in cows in the periparturient period. Qualitative and quantitative aspects of several neutrophil cell functions before and during experimentally induced infections are briefly discussed. PMID- 8009820 TI - Growth and skeletal development in the dog in relation to nutrition; a review. AB - Longitudinal growth of the appendicular skeleton in the growth plates and the adjacent metaphyseal area includes chondrocyte differentiation, proliferation, maturation, and hypertrophy in the physis and bone (re-) modelling in the metaphysis. The rate and extent of longitudinal growth are regulated by interactions between biomechanical factors and endogenous growth regulators, i.e., systemic endocrine factors, and local para or autocrine factors, that act on the growth plate chondrocytes. The most important endogenous regulators of growth and skeletal development are growth hormone (GH) and insulin-like growth factors (IGFs), and calciotropic hormones, i.e., parathyroid hormone (PTH), vitamin D (vitD), and calcitonin (CT). The biochemistry, synthesis, secretion, target organs, and effects of these endogenous factors are reviewed, and the calcium homeostatic mechanisms, dietary intake, bone turnover, and calcium excretion are discussed. Energy, protein, and calcium are nutritional factors of great importance to (skeletal) growth. The effects of low and high dietary intake of these nutrients are discussed, especially with reference to longitudinal growth and disturbances in endochondral ossification. PMID- 8009821 TI - Squamous metaplasia in the salivary glands of canaries (a case report). AB - Squamous metaplasia of the glandular epithelium was found in the palatine salivary glands of two canaries, originating from a flock in which there was a variable intake of egg food. The histological changes, in combination with the history, indicate a vitamin A deficiency as a result of a selective intake of food as the most likely aetiology. PMID- 8009822 TI - In vitro transport of carbon in the trachea of veal calves. AB - Carbon transport was studied in vitro in preparations of trachea and bronchus from veal calves. The mean velocity varied from 4.2 mm/min in the main bronchi to 6.3 mm/min in the ventral trachea. In some locations no transport was observed. Stereomicroscopic evaluation of Alcian blue-phloxine stained mucosal surfaces revealed differences in the appearance of the mucus layer between locations with and without mucus transport. It is concluded that quality and integrity of the mucus layer play an important role in mucus transport. PMID- 8009823 TI - Sedation of wild boar (Sus scrofa) and red deer (Cervus elaphus) with medetomidine and the influence on some haematological and serum biochemical variables. AB - Medetomidine, an alpha-2 agonist, was tested for the sedation of wild boar (Sus scrofa) (n = 6) and red deer (Cervus elaphus) (n = 7). The effectivity of this drug and the dose required for handling, blood sampling, and minor surgery were established for both species. In addition the effect of medetomidine sedation on haematological and serum biochemical variables was studied. All animals used were clinically normal females aged approximately 1.5 years. The minimal dose required to sedate a wild boar was 80 micrograms/kg (i.m.). The induction time was 35-50 min, and the sedation time was between 40 and 55 min; however, the sedation was insufficient. The minimal dose required for red deer was 80 micrograms/kg (i.m.). Blood sampling and minor surgery could be carried out without any problem. The induction time was 21-29 min and the sedation time was between 120 and 210 min. The alpha-2 antagonist atipamezole (300 micrograms/kg) was effective in reversing sedation, with recovery occurring between 3 and 9 min. Medetomidine sedation influenced the blood composition of wild boar. Haemoglobin and packed cell volume decreased by about 20% (P < 0.002), total serum protein content decreased slightly (P = 0.011), and the glucose concentration nearly doubled (P = 0.002). PMID- 8009824 TI - A Rev protein is expressed in caprine arthritis encephalitis virus (CAEV) infected cells and is required for efficient viral replication. AB - Caprine arthritis encephalitis virus (CAEV) is a lentivirus that is closely related to visna virus and more distantly related to the human lentivirus human immunodeficiency virus 1 (HIV-1). Like other lentiviruses, the genome of CAEV contains multiple small ORFs that encode viral regulatory proteins. Sequence analysis of the CAEV genome and cDNAs generated from mRNA in infected cells has suggested that one of these ORFs encodes a protein (Rev-C) that is analogous to Rev of visna virus and HIV. Antibodies generated to a carboxy-terminal peptide of the rev ORF immunoprecipitate an 18-kDa protein from cells transfected with the Rev cDNA clone. Immunoprecipitation and immunofluorescence analysis of CAEV infected ovine primary cells show that the product of the rev ORF is expressed during infection and localizes to the nucleolus of infected cells. Also, sera from CAEV-infected goats specifically immunoprecipitates an in vitro-translated product from the full-length Rev cDNA clone as well as that from the unique second open reading frame of Rev-C which shows that the Rev-C protein is expressed during natural CAEV infection of animals. Insertion of either a mutation that creates two stop codons in the unique second open reading frame of Rev-C or a mutation in the basic domain of Rev-C into the CAEV infectious molecular clone renders the virus unable to replicate in primary goat synovial membrane cells. Analysis of the RNA and proteins produced from both Rev-deficient clones indicates that they are defective in the accumulation of structural gene mRNAs in the cytoplasm as well as in synthesis of structural proteins compared to the wild-type CAEV clone. These data indicate that CAEV encodes a Rev protein that is required for efficient viral replication in culture. PMID- 8009825 TI - Defective processing of human adenovirus 2 late transcription unit mRNAs during abortive infections in monkey cells. AB - Growth of human adenoviruses is severely restricted in monkey cells. We examined the synthesis of mRNAs from the Ad2 late transcription unit (LTU) in abortively infected monkey cells at late times in infection. All L2, L3, and L5 mRNAs were absent or drastically reduced in abortive infections. Most L1 and L4 mRNAs were also greatly decreased in abortive infections; however, a single large messenger was produced from each of the L1 and L4 families, at levels approaching those found in productive infections. The pattern of i-leader containing mRNAs was also changed in abortive infections. These defects could be corrected in monkey cells by the presence of SV40 T antigen or an altered adenoviral DNA binding protein. These defects in late gene expression in abortive infections could not be attributed to differences in transcription along the LTU or levels of DNA replication. In abortively infected cells, nuclear levels of L5 mRNA were decreased 2 to 6 fold, while cytoplasmic levels were decreased over 200-fold. These findings imply a general defect in processing of viral mRNAs, most likely due to defective splicing and/or transport, during abortive infections. PMID- 8009826 TI - Structural genes, not the LTRs, are the primary determinants of reticuloendotheliosis virus A-induced runting and bursal atrophy. AB - Reticuloendotheliosis virus strain A (REV-A) and chicken syncytial virus (CSV), two replication competent avian retroviruses, differ in the extent to which they induce a runting syndrome that includes anemia, lymphoid organ atrophy, and reduced body size. We have isolated an infectious clone of CSV, the less pathogenic of the two viruses, and compared it to REV-A. Partial DNA sequence analysis suggests that it differs from REV-A by no more than 1 to 2% at the nucleotide level. Analysis of viral interference indicates that these two viruses use the same cell receptor for infection of both fibroblasts and hematopoietic cells, DNA sequence of the CSV and REV-A long terminal repeats (LTRs) reveals that these structures differ principally by two small insertions (5 and 19 bp) present in the U3 region of REV-A. The larger of these may encode enhancer sequences that have been reported to influence transcription rates in vitro. Measurement of steady-state levels of viral RNA in infected cells, however, as well as circulating virus in infected chicks indicates that the different pathogenic responses elicited by these two viruses are not due to large differences in viral transcription or replication. Chimeric viruses were constructed in which the LTRs from one virus were used to express the structural genes of the second virus. Infection of 1-day-old chicks by parental virus as well as the reciprocal chimeric constructs demonstrated that the ability to induce both runting and bursal atrophy segregated with the structural genes of REV-A. Infection of birds with additional chimeric viruses in which the env genes of REV-A and CSV were exchanged indicated that the pathogenic response resulting from REV-A infection was due to at least two regions of the viral genome encoding structural genes. PMID- 8009827 TI - Membrane rearrangement and vesicle induction by recombinant poliovirus 2C and 2BC in human cells. AB - Poliovirus (PV)-infected cells undergo extensive proliferation and rearrangement of intracellular smooth membranes to generate vesicles on which viral RNA replication occurs. PV proteins 2C and 2BC are known to be tightly associated with these membranous replication complexes and have been proposed to be involved in the formation of these virus-induced vesicles. We have expressed these proteins, and proteins with mutations in the putative nucleotide (NTP) binding motifs, in human cells using recombinant vaccinia viruses and T7 RNA polymerase directed transcription. To ascertain the subcellular localization properties of these proteins in the absence of other PV proteins and to determine whether they induced ultrastructural changes, cells expressing 2C and 2BC proteins were examined by immunofluorescence (IF) microscopy, electron microscopy (EM), and immuno-EM (IEM). The cytoplasm of cells expressing either 2C or 2BC exhibited vesicles of 50-350 nm in diameter, which resembled those found in PV-infected cells. Both 2C and 2BC were associated with these vesicles. Mutations in the putative NTP binding motif did not affect vesicle induction by 2C or 2BC. Despite the membrane reorganization and vesicle formation induced by 2C and 2BC proteins, no enhanced synthesis of lipid was observed. Guanidine hydrochloride at a concentration that inhibits PV replication, did not have significant effects on the IF patterns of either 2C or 2BC. An additional prominent alteration in cells expressing 2C, but not 2BC, was the formation of extensive tubular membrane structures with a myelin-like arrangement in the lumen of the rough endoplasmic reticulum. IEM analyses showed that 2C was associated with these structures. In the presence of other PV proteins, the tubular membrane structures induced by 2C were not detected. These structures are not observed in poliovirus-infected cells, but likely indicate a novel property of 2C that induces a complex interaction with intracellular membranes. PMID- 8009828 TI - Deletion analysis defines a carboxyl-proximal region of Sendai virus P protein that binds to the polymerase L protein. AB - The Sendai virus RNA polymerase complex consists of two viral proteins, L and P, which must be coexpressed in order to form the active enzyme. Pulse-chase experiments show that the L protein is unstable when synthesized in the absence of the P protein, but is stable in the P-L complex. Using sequential deletions in the P protein (568 amino acids), we have mapped the site on the P protein where the L protein binds by co-immunoprecipitation and gradient sedimentation analyses. The L-binding site residues in the C-terminal half of the P protein, since deletion of up to amino acid 324 of P protein does not affect complex formation. The L-binding site was mapped to a region of P protein encompassing amino acids 412-478. This region lies between the previously mapped amino acid regions which form the nucleocapsid-binding domain (amino acids 345-411 and 479 568). The data suggest that the L and NP protein-binding domains on P protein do not overlap. PMID- 8009830 TI - Functional dissection of the ie2 gene product of the baculovirus Autographa californica nuclear polyhedrosis virus. AB - The PstI-N genomic fragment of Autographa californica nuclear polyhedrosis virus (AcNPV) encodes an immediate-early protein, IE2, that functions as a promiscuous transactivator of other early viral promoters and heterologous promoters both in vivo and in vitro. IE2 contains several sequence motifs that are common to transcriptional activators. We have employed site-directed mutagenesis coupled with transient-expression assays to identify the amino acid sequences of IE2 that are essential for transactivation. Sequential deletion of amino-terminal sequences of IE2 gradually decreased the activity of the protein. Carboxy terminal truncations of IE2 resulted in a dramatic loss of transactivation activities. Analysis of IE2 internal-deletion mutants demonstrated that the acidic amino acid-rich region between amino acids 198 and 206 possessed significant transactivation potential for all target promoters tested. In addition, squelching phenomena exhibited by wild-type IE2 and IE2 deletions containing the acidic amino acid-rich region indirectly demonstrated that this region may be involved in interactions with factors of the basic transcription machinery. PMID- 8009829 TI - Modulation of vimentin, the CD40 activation antigen and Burkitt's lymphoma antigen (CD77) by the Epstein-Barr virus nuclear antigen EBNA-4. AB - The growth transformation of human B cells by Epstein-Barr virus (EBV) is controlled by the coordinate expression of 10 latent viral genes. This transforming capacity is believed to be fundamental to the involvement of the virus in human malignancies of B cell origin. EBV-negative Burkitt's lymphoma (dG75) clones stably expressing one of these EBV-coded antigens, EBNA-4, have been established using an episomal-based plasmid. EBNA-4 expression was found to upregulate the cytoskeletal protein vimentin as well as surface expression of the activation antigen CD40. In addition, the presence of EBNA-4 resulted in downregulation of the Burkitt's lymphoma-associated antigen (BLA/CD77). These studies show for the first time that EBNA-4 modulates the expression of several cellular genes implicated in cell-growth transformation. PMID- 8009831 TI - Cloning and characterization of the guinea pig cytomegalovirus glycoprotein B gene. AB - Unlike other small animals, cytomegalovirus (CMV) infection of the guinea pig results in transplacental passage and intrauterine infection of the fetus. These features make the guinea pig model ideal for studying vaccine strategies designed to prevent congenital infection. Unfortunately, little is known about immunogenic guinea pig CMV gene products. In other animal cytomegaloviruses, a major target of the host immune response is the glycoprotein B (gB, gp UL 55) gene product. Using DNA probes containing human CMV gB sequences, the gB gene homolog of the guinea pig cytomegalovirus was identified, cloned, and sequenced. The gpCMV gB gene maps to a region spanning portions of the HindIII K, Q, and P fragments of the gpCMV genome. DNA sequence analysis identified an open reading frame of 2706 nucleotides capable of encoding a protein of 901 amino acids. Extensive similarity to the human and murine gB proteins was noted with 42% identity at the amino acid level. The predominant gpCMV gB mRNA is a 6.8-kb transcript with the expression kinetics of an early gene. RNase protection and primer extension analyses indicated that gB mRNAs were transcribed from two different initiation sites corresponding to distinct TATA elements. Polyclonal antisera prepared against a synthetic peptide derived from amino acid sequences within the ORF identified a 58-kDa virion-associated protein representing the cleaved COOH terminus (gp 58) of the gpCMV gB molecule. The molecular characterization of gpCMV gB should facilitate studies of vaccine strategies in the guinea pig model of congenital CMV infection. PMID- 8009832 TI - Functional significance of the dinucleotide bulge in stem-loop1 and stem-loop2 of HIV-2 TAR RNA. AB - Human immunodeficiency virus types 1 and 2 (HIV-1 and HIV-2) encode related proteins called Tat-1 and Tat-2, respectively, that bind directly to the TAR RNA element contained at the 5' ends of viral transcripts and thereby stimulate transcription through an as yet unidentified mechanism. The determinants in the HIV-1 TAR element (TAR-1) that specify binding by the Tat-1 protein have been extensively characterized, while little is known about determinants in the HIV-2 TAR element (TAR-2) that specify binding by the Tat-2 protein. The HIV-2 TAR RNA element (TAR-2) is known to be composed of two stem-loop structures. A dinucleotide bulge is found in each stem of TAR-2 RNA, analogous to the crucial trinucleotide bulge in the single stem-loop of HIV-1 TAR RNA that is the primary binding determinant for binding by the HIV-1 Tat protein. Our results of a nuclease digestion analysis demonstrated that the 5' proximal bulge in TAR-2 is significantly less sensitive to digestion by single-strand specific nucleases than the 3' distal bulge, suggesting that the 5' bulge may be involved in tertiary interaction with other regions of TAR RNA. Deletion of both bulges reduced binding in vitro by the Tat-2 protein and largely abolished transactivation in vivo by Tat-2. Deletion of either bulge alone simplified the pattern of protein/RNA complexes in a gel shift assay, but did not reduce the overall binding affinity of Tat-2. Deletion of the 5' bulge reduced Tat-2 transactivation in vivo to a level approximately 30% that of wild-type TAR-2, while deletion of the 3' bulge had no measurable effect in vivo. Our results suggest that each dinucleotide bulge specifies a Tat-2 binding site, but in the wild-type TAR-2 element the 3' bulge binding site does not appear to be utilized in vivo. PMID- 8009833 TI - Primate T-lymphotropic virus type I LTR sequence variation and its phylogenetic analysis: compatibility with an African origin of PTLV-I. AB - Due to the low evolutionary rate and the limited horizontal transmission of human T-lymphotrophic virus type I (HTLV-I), its phylogenetic analysis reveals the movements and contacts of ancient populations. Since simian strains cannot be distinguished from human strains by phylogenetic criteria, this virus has appropriately been called primate T-lymphotropic virus type I (PTLV-I). We sequenced the LTR of six PTLV-I strains: three HTLV-I strains from African patients with tropical spastic paraparesis (TSP) (Equateur, Zaire), two laboratory HTLV-I strains of Japanese origin, MT-2 and MT-4, and one STLV-I from a baboon of the primate center in Sukhumi, Georgia. We applied four phylogenetic inference methods: neighbor-joining (NJ), unweighted pair group method using arithmetic averages (UPGMA), Fitch and Wagner parsimony (pars), and maximum likelihood (ML), to these 6 LTR sequences and 18 published LTR sequences (cosmopolitan, African, and Melanesian HTLV-I strains and African and Asian STLV I strains). Three major HTLV-I subtypes can be identified with all four methods: the cosmopolitan HTLV-Ia, the central African HTLV-Ib, clearly descendant from a STLV-I CH-like African ancestral simian strain, and the Melanesian HTLV-Ic, probably descendant from an Asian STLV-I strain. We observe a segregation of PTLV I sequences according to their geographical origin and not according to host species. The Zairean strains form a cluster closely related to an STLV-I strain isolated from a chimpanzee (STLV-I CH) and distinct from western African strains, which belong to the cosmopolitan subtype of HTLV-I. The Sukhumi STLV-I strain found in a captive-born baboon was of Asian descent. We experienced rooting problems with UPGMA when using HTLV-II as an outgroup. Concordant results with all four methods were obtained by eliminating HTLV-II LTR sequence fragments with bad alignment to HTLV-I. This resulted in a HTLV-II root node on the African STLV I TAN90 terminal branch (with bootstrap values above 92% for the NJ and pars methods) and not on the Asian STLV-I PtM3 branch, as has been derived by others based on their use of UPGMA. The results of the analyses also support a higher evolutionary rate of PTLV-I in Asia, implying that the trees obtained with the NJ and ML methods have a higher reliability. These results are more compatible with an ancient African origin of PTLV-I than with an Asian origin. PMID- 8009834 TI - Analysis of binding elements in the human immunodeficiency virus type 1 genomic RNA and nucleocapsid protein. AB - We previously used RNA gel mobility shift assays to demonstrate specific binding of the HIV-1 gag precursor polyprotein and nucleocapsid (NC) protein to HIV-1 RNA and to map the binding elements in each species by mutagenesis. Here we report finer mapping of binding elements in the HIV-1 genomic RNA and NC protein, performed by analyzing the binding behavior of fragments of each species in the gel shift assay. With regard to the RNA, the strongest binding activity resided in a 120-nucleotide segment flanking the gag start codon, containing three potential stem-loop structures. Binding analysis of various combinations of these three potential stem-loop structures and their flanking sequences revealed that no one element could bind to the gag polyprotein or NC protein as well as the entire 120-nucleotide segment. Mutational analysis of the NC protein showed that two nonoverlapping regions exhibited specific binding for HIV-1 RNA. Each region includes a Cys-His box, though each box could not bind to HIV-1 RNA on its own. In construct lacking both boxes exhibited primarily nonspecific RNA-binding activity. PMID- 8009835 TI - Productive infection of human endometrial stromal cells by human cytomegalovirus. AB - Cultured endometrial stromal cells were susceptible to productive human cytomegalovirus (HCMV) infection. Infection of endometrial stromal cells resulted in pronounced cytopathic effects including cell rounding and aggregation, fusions, and some lysis, although not in the synchronous fashion observed in infected fibroblasts. The aggregation events were reminiscent of normal endometrial stromal cell responses to cyclical estrogen/progesterone levels. Immunofluorescence analysis demonstrated expression of viral gene products suggesting a productive virus infection. One-step growth analysis showed that infectious virus was produced but the titers were two logs lower than those obtained in fibroblasts even though HCMV DNA accumulated to similar levels in both cell types. In contrast, viral DNA replication was greatly reduced in endometrial stromal cells immortalized with a temperature-sensitive SV40 large T gene at both permissive and nonpermissive temperatures. A more detailed analysis of viral gene expression by Northern blotting revealed earlier appearances and greater initial levels of viral transcripts in endometrial stromal cells. No HCMV gene expression was observed at 120 hpi in these cells even though half of the cells were still intact and cellular gene expression was functional. Since this was the time of peak virus production, it seems plausible that reduced viral gene expression at late times p.i. was a major contributor to the reduced titers observed in endometrial stromal cells. These in vitro results coupled with in vivo observations by others of endometritis associated with HCMV suggest that further investigation into the effects of HCMV on the endometrium is warranted. PMID- 8009836 TI - Sequences of 10 variants of the satellite-like RNA-3 of groundnut rosette virus. AB - Ten cDNA clones, representing the satellite-like RNA-3 associated with five different isolates of groundnut rosette virus, were prepared and sequenced. The sequences are at least 87% identical, but differences associated both with symptom differences and with geographical origin were found. The sequences contain up to five potential open reading frames (ORFs), of which three are in the strand that is most abundant in infected plants and two are in the complementary strand. Only one of these ORFs is present in all 10 sequences. Neither the sequence of RNA-3 nor that of its potential translation products had significant similarities to sequences in the databases. PMID- 8009837 TI - RNA structural requirements for stability and minus-strand synthesis in the dsRNA bacteriophage phi 6. AB - Bacteriophage phi 6 has a genome consisting of three segments of double-stranded RNA designated L, M, and S. Each virion contains one of each genomic segment. Empty procapsids can package plus-strand transcripts of the genomic segments if the 5' regions are intact. Minus-strand synthesis takes place if all three segments are packaged and if the 3' end of the segment is intact. The 3' ends of the segments contain four hairpin structures within a region of high sequence conservation. We now show that removal of parts of this region leads to progressive but limited loss of ability to support minus-strand synthesis. The defective 3' ends can be corrected by heterologous recombination with the termini of other segments. Segments that have small deletions in the conserved region and that support apparently normal minus-strand synthesis are highly recombinogenic. PMID- 8009838 TI - Biological importance and cooperativity of HIV-1 regulatory gene splice acceptors. AB - The replication of HIV-1 mutants containing altered splice acceptor sequences was studied. The splice acceptor sites 5' of the essential tat and rev AUG codons were altered to eliminate specifically spliced species from the viral repertoire of mRNAs. All splice site mutants were attenuated or fully defective. Mutation of the tat splice acceptor (exon 4) caused loss of the mRNA species containing exon 4 and resulted in an attenuated but replication-competent phenotype. Mutation of the rev splice acceptor sites resulted in viral genomes that failed to propagate in vitro. Mutation of the more 5' of the two major rev acceptors (exon 4A) caused loss of the mRNA species containing exon 4A together with a compensatory increase in use of the more 3' of the rev acceptors (exon 4B). Mutation of the splice acceptor for exon 4B caused the unexpected loss of both exon 4A- and 4B containing mRNAs. In addition to these effects on the rev splice acceptors, mutations at the 4A and 4B sites also resulted in decreased use of the tat splice site (exon 4) located 175 nucleotides upstream. These effects on utilization of the tat splice acceptor site may explain the requirement for tat to efficiently complement these mutants. The 4A mutant was complemented by tat but not by rev. The 4B mutant was complemented by rev but required both tat and rev for maximum complementation. These data suggested a cooperativity among these splice sites necessary for efficient viral replication. They also indicated that while viral replication persisted at low levels in the absence of splicing to the known site 5' of the tat AUG, failure to splice to at least one of the two major sites 5' of the rev AUG resulted in insufficient rev activity for replication competence. PMID- 8009839 TI - Murine cytomegalovirus is present in both chronic active and latent states in persistently infected mice. AB - Cytomegalovirus induces serious disease in immunosuppressed individuals, often from an "activated" persistent infection. Whether the infection is chronically active or latent is unknown. Using murine cytomegalovirus (MCMV) in mice as a model system, we examined persistent infections in spleen, lung, and bone marrow of infected animals. At 28 days after infection, no virus could be recovered from any organs tested except salivary glands, and here, virus was cleared by 48 days. Virus could be retrieved at all times by cocultivation of spleen or lung with permissive cells. In addition, MCMV DNA was always present in spleen, lung, and bone marrow. After acute infection, RNA from the MCMV immediate early-1 (ie-1) gene was routinely found only in the lung. In spleen and bone marrow, only one sample from each organ examined at these times contained ie-1 RNA, and the RNA in these two samples was present at levels comparable to that found in acute infection. This suggests that the virus had reactivated. The ie-1 RNA found in the lung was present at a much lower RNA:DNA ratio than that found at early times. Taken together, these results indicate that persistent MCMV exists simultaneously in both chronic active and latent states. PMID- 8009841 TI - Vaccinia virus core protein VP8 is required for virus infectivity, but not for core protein processing or for INV and EEV formation. AB - A recombinant vaccinia virus, vDW4, has been constructed in which the L4R gene encoding the VP8 core DNA-binding protein is inducibly regulated by IPTG (isopropyl beta-D-thiogalactopyranoside). This virus produced normal-sized plaques in the presence of IPTG, but tiny plaques in the absence of inducer. Production of infectious progeny virus was reduced by 97% when VP8 synthesis was repressed and immature virions which had defective interactions between the granular viroplasm and the surrounding virion membrane were evident. However, despite the formation of these abnormal immature virions, virus maturation was able to proceed with the production of mature intracellular naked virus and extracellular enveloped virus particles of normal density. These mature particles were produced to approximately 80% of wild-type levels, but were around 100-fold less infectious. Consistent with the formation of mature virions, the repression of VP8 synthesis did not inhibit proteolytic processing of the major core proteins p4a and p4b. These results suggest that VP8 is required for correct association of the viroplasm and the immature virion envelope and that VP8 must be present during virus assembly for the production of fully infectious progeny virus. PMID- 8009840 TI - Recent influenza A (H1N1) infections of pigs and turkeys in northern Europe. AB - The most recent introduction of an avian influenza A virus without reassortment into mammals occurred in 1979 when H1N1 strains could be isolated from diseased pigs in northern Europe. This newly introduced avian virus formed a stable lineage in pigs and, in the meantime, spread all over Europe. In 1991 highly pathogenic H1N1 strains closely related to a contemporary swine virus were isolated from turkeys of a breeding farm near Bremen, Germany. Outbreaks in several farms in Germany, France, and the Netherlands indicate that the "avian like" swine viruses can easily be reintroduced into an avian population causing severe economical losses. PMID- 8009842 TI - The SPI-1 gene of rabbitpox virus determines host range and is required for hemorrhagic pock formation. AB - Wild-type rabbitpox virus (RPV) and cowpox virus (CPV) produce red hemorrhagic lesions or pocks upon infection of the chicken chorioallantoic membrane (CAM) of 11-day-old embryonated chicken eggs. However, white, nonhemorrhagic pock variants arise spontaneously within wild-type (wt) populations of either virus at a frequency of about 1%, reflective of complex deletions/rearrangements in the termini of the viral DNA. A subpopulation of the RPV white-pock mutants fail to plaque on pig kidney (PK-15) cells and are referred to as host-range (hr) mutants. In the case of CPV, white-pock formation has been linked to mutations in the SPI-2 (crmA) gene. We show that five spontaneous RPV white-pock host-range mutants (RPV mu hr8sm, RPV mu hr23, RPV mu hr28, RPV mu hr30, and RPV mu hr31) each contain a SPI-2 (crmA) gene and express the crmA protein but lack instead a functional SPI-1 gene. Two other spontaneous RPV white-pock mutants, RPV mu 9 and RPV mu 12, which plaque on PK-15 cells (nonhost-range mutants) contain and express a SPI-1 gene but lack instead a functional SPI-2 gene. Targeted disruption of either the SPI-1 or SPI-2 genes of wtRPV, but only the SPI-2 gene of wtCPV, generates mutants which produce white pocks. The RPV delta SPI-1 mutant fails to plaque on PK-15 or human A549 cells, whereas the RPV delta SPI-2 mutant has a normal host range. No changes in host range compared to wtCPV for either the CPV delta SPI-1 or CPV delta SPI-2 mutants were noted. These differences in phenotypes observed between the two viruses may be reflective of either small sequence variations between the highly conserved SPI-1 or SPI-2 genes or the aggregate phenotypes provided by the other remaining genes. PMID- 8009843 TI - Autographa californica nuclear polyhedrosis virus, PDV, and ECV viral envelopes and nucleocapsids: structural proteins, antigens, lipid and fatty acid profiles. AB - Autographa californica nuclear polyhedrosis virus (AcMNPV) infection results in the production of two types of infectious, enveloped viruses. As both of these viral forms play significantly different roles in the virus life cycle, the different functional characteristics in the roles of the virus may be explained, in part, by the protein and lipid composition and source of the viral envelopes. Both viruses utilize different maturation and envelopment strategies: Extracellular virus (ECV) obtains an envelope by budding from the host cell plasma membrane, while the envelope of polyhedra-derived virus (PDV) is obtained within the nucleus of the host cell. There is compelling evidence for differences between ECV and PDV structural proteins; however, no previous study directly compares ECV and PDV purified from the same source and little data are available on the protein and lipid composition of the viral envelopes. This study begins the systematic comparison of ECV, PDV, and their envelopes to target proteins for use as probes to study the molecular and biochemical basis of viral envelopment within the nucleus. AcMNPV ECV and PDV were isolated from infected Spodoptera frugiperda cells and fractionated into their respective envelope and nucleocapsid fractions. The structural protein, glycoprotein, and phosphoprotein composition of ECV, PDV, and their envelope and nucleocapsid fractions are analyzed and compared, and antigens of ECV and PDV viral envelope are identified. A number of structural proteins are different between ECV and PDV. ECV is enriched for proteins at 67, 45, and 35 kDa, while proteins at 89, 70, 60, 50, and 25 kDa are enriched in PDV. At least two proteins, PDV-E66 and PDV-E43, are identified to be specific for the PDV envelope. There are more N-glycosylated proteins in ECV than in PDV, with ECV-specific proteins found at 137, 128, 89, 45, and 40 kDa. PDV glycoproteins are 70, 53, 49, 42, 40, and 31 kDa. Most phosphoproteins of both ECV and PDV are predominantly found in the viral envelopes. The predominant phosphoprotein of ECV is 85 kDa, whereas PDV major phosphoprotein is 36 kDa. This study presents the first report of the phospholipid and fatty acid content of ECV and PDV viral envelopes. The major phospholipid of ECV is phosphatidylserine (50%), while phosphatidylcholine and phosphatidylethanolamine are the major phospholipids of PDV (39 and 30%, respectively). Since PDV is enveloped within the nucleus of the host cell, the PDV phospholipid composition is compared with the phospholipid composition of purified S. frugiperda (Sf9) nuclei and this analysis demonstrates significant differences between these two membrane systems. PMID- 8009844 TI - Abnormal processing of a recombinant feline leukemia virus envelope polyprotein and its interference with subgroup C virus infection. AB - Processing of the env polyprotein of a noninfectious feline leukemia virus (FeLV) recombinant, named r6gp, was examined in human-transfected cells. The r6gp provirus was previously generated in the frame of FeLV, subgroup B, GA clone with substitution of all but 40 C-terminal amino acid sequences of the surface glycoprotein (SU) from an endogenous FeLV provirus element (CFE-6). Although r6gp produced a normal size (85 kDa) env glycoprotein precursor, the product, unlike the precursor of the parental virus, was neither additionally glycosylated nor further processed into mature env proteins. Biochemical observations were consistent with the idea that the chimeric env polyprotein was trapped in the endoplasmic reticulum (ER) and were directly supported by immunofluorescence microscopy analyses. Interestingly, the residence of the chimeric protein in the ER specifically interfered with FeLV, subgroup C (Sarma) virus infection but not the parental FeLV-B virus infection. Since FeLV-C provirus sequences could be readily detected in the infected cells, it appeared that r6gp env expression did not block entry of the challenge virus. While FeLV-B and CFE-6 env genes share an extensive overall sequence homology, a variable region (region VI) of CFE-6 near the C-terminus of SU, which was retained in the r6gp construct, exhibits a considerably higher degree of homology to FeLV-C than FeLV-B. Thus, we propose that region VI is involved in conferring specificity for the env polyprotein oligomerization in the ER, and that co-oligomerization of the trapped r6gp env with FeLV-C is the reason for specific interference with FeLV-C infection. The results also demonstrate for the first time a functional abnormality of a recombinant FeLV env gene which is structurally similar to those commonly detected in FeLV-induced feline lymphosarcomas. PMID- 8009845 TI - Sequence analysis of the trailer region of sonchus yellow net virus genomic RNA. AB - The sequence of the 5' terminus (or the "trailer" region) of the minus-sense RNA genome of sonchus yellow net virus (SYNV) was determined by dideoxynucleotide termination sequencing of purified viral RNA and cloned cDNAs. The 5'-terminal nucleotide was identified by nuclease P1 digestion of 32P-end-labeled genomic RNA followed by polyethyleneimine cellulose chromatography. The trailer sequence occupies positions 13,561 to 13,720 relative to the 3' end of the genomic RNA and is composed of 160 nucleotides (nt) adjacent to a dinucleotide forming a portion of the "gene junction" sequence at the terminus of the L protein gene. The trailer sequence is longer than the 144-nt plus-strand leader RNA transcribed from the 3' end of the genomic RNA and is the longest trailer sequence yet reported among the nonsegmented negative-strand viruses. As is characteristic of other rhabdovirus genomes, the 3' and 5' termini of the SYNV genome are complementary and are capable of forming a panhandle structure involving 16 of the 18 terminal nucleotides. However, there is no obvious direct nucleotide sequence relatedness between the SYNV trailer sequence and those of animal rhabdoviruses and paramyxoviruses. The existence of a minus-strand leader RNA of the same polarity as the trailer sequence could not be detected in nucleic acid extracted from infected plants under hybridization conditions suitable for detection of the plus-strand leader RNA. In this regard, SYNV differs from vesicular stomatitis virus and is similar to other rhabdoviruses which also fail to accumulate detectable minus-strand leader RNAs. PMID- 8009846 TI - Interaction between tubulin and the viral matrix protein of vesicular stomatitis virus: possible implications in the viral cytopathic effect. AB - The matrix (M) protein of vesicular stomatitis virus has been shown to induce the rounding of cells. Experiments were performed in order to define the mechanism by which M protein could cause this cytopathic effect (CPE). Immunofluorescence experiments performed on infected cells indicate that cellular rounding coincides with the disruption of the microtubular network. Immunoprecipitation of M protein or tubulin in infected cell extract demonstrates an association of these two proteins in vivo. We show that M protein is capable of interacting in vitro with tubulin in both its polymerized and nonassembled forms. Studies using proteolytically cleaved proteins indicate that this interaction occurs via the highly basic N-terminal domain of M protein and the highly acidic C-terminal region of tubulin. Furthermore, a thermosensitive mutant (tsG33) containing a mutation in the matrix protein gene which is unable to induce CPE at nonpermissive temperature interacts with tubulin with a lower affinity. These results demonstrate that M protein interacts with tubulin in vivo and in vitro and strongly suggest that CPE is caused by this interaction. PMID- 8009847 TI - Expression and characterization of the two outer capsid proteins of African horsesickness virus: the role of VP2 in virus neutralization. AB - African horsesickness virus (AHSV) is a gnat-transmitted member of the Orbivirus genus of the Reoviridae family. The virus has a genome of 10 double-stranded RNA species (L1-L3, M4-M6, S7-S10). The L2 and M6 genes of AHSV serotype 4 (AHSV-4) which encode the outer capsid proteins VP2 and VP5, respectively, were inserted into recombinant baculoviruses downstream of the baculovirus polyhedrin, or p10 promoters. Recombinant baculoviruses expressing VP2, VP5, or VP2 and VP5 proteins of AHSV-4 were isolated. The expressed AHSV proteins were similar in size and antigenic properties to those of viral AHSV-4. Expressed VP2 and VP5 proteins were purified to homogeneity and utilized to differentiate sera from vaccinated and infected horses. Antigens were also used to determine whether any other AHSV serotypes are related to AHSV-4. The results indicated that AHSV-4 is distantly related to some serotypes (e.g., AHSV-2, -6, and -9) but not to others (e.g., AHSV-5 and -7). Hyperimmune monospecific antisera raised in rabbits with purified VP2 neutralized the infectivity of a virulent strain of AHSV-4 isolated from an infected horse during a recent outbreak of the disease in Spain. PMID- 8009848 TI - Human rhinovirus 14 complexed with fragments of active antiviral compounds. AB - Crystallographic studies of human rhinovirus 14 (HRV14) crystals soaked with fragments of antiviral WIN compounds, at high concentrations (82-200 micrograms/ml), show the compounds bind into the hydrophobic beta-barrel (WIN pocket) of VP1. Two of these short compounds (5-[3,5-dimethyl-4-hydroxyphenyl]-2 methyltetrazole and phenol oxazoline) cause conformational changes in the virus similar to the active, longer WIN compounds. In addition, thermostabilization studies suggest these short WIN compounds provide some stability to the HRV14 capsid. We conclude that the short compounds appear to mimic the cellular cofactors observed in the hydrophobic pocket of VP1 for some picornaviruses. Both cofactors and short WIN compounds bind into the pocket, cause conformational changes in VP1, and provide a small degree of virion stabilization but are unlikely to inhibit attachment. Three specific binding sites for dimethyl sulfoxide (DMSO), used as solvent, were also identified. One of the DMSO molecules binds into the drug binding pocket near the pocket opening, while the other two bind in the canyon near the VP1 protomer-protomer interface. PMID- 8009849 TI - Microevolution of Sabin 1 strain in vitro and genetic stability of oral poliovirus vaccine. AB - Mutants consistently accumulating in Sabin 1 poliovirus during serial passaging in vitro were identified by sequence heterogeneity assay and quantitated using mutant analysis by PCR and restriction enzyme cleavage (MAPREC). Only four unstable genomic sites were identified in virus passaged 10 times in African green monkey kidney (AGMK) cells, and eight sites in virus passaged in Vero cells. Mutations accumulated both in untranslated regions of RNA (nucleotides 480, 525 and 7441) and in coding sequences, as missense (nucleotides 1449, 4944, and 6203) or silent (nucleotides 1123 and 1141) mutations. The most prominent selectable mutations were found at complementary nucleotides 480 and 525 of the 5'-untranslated region (5'-UTR) of the Sabin strain, changing the G:U pair in F domain to either A:U or G:C variants. These two variants have been shown previously to have an increased neurovirulence in monkeys. The G:C variant accumulated during passage in Vero cells, while A:U variant accumulated in CV-1 cells. Virus passaged in AGMK cells accumulated both variants. Higher temperature (37 instead of 34 degrees) strongly favored selection of mutants in Vero cells, had a smaller effect on mutant accumulation in AGMK cells, and had no effect in CV-1 cells. Monopools of type 1 oral poliovirus vaccine (OPV) made by seven manufacturers were found to contain both 480-A and 525-C revertants at a combined level of 1.1-2.7%. Viral samples with increased amounts of these revertants had higher neurovirulence in monkeys. Our results suggest that quantitation of these reversions by MAPREC may be prognostic for results of the monkey neurovirulence test (MNVT) and can be used for monitoring type 1 OPV consistency. PMID- 8009850 TI - The X protein of hepatitis B virus has a ribo/deoxy ATPase activity. AB - The X protein (pX) of hepatitis B virus (HBV) is a general transcription regulator and directly associated with the transcription machinery. pX cannot bind DNA directly but interacts with cellular factors that bind the regulatory elements. There is an accumulation of evidence concerning different activities exerted by pX in transfected cells; nevertheless, the function and the biochemical properties of the protein are unknown. Biochemical analysis of bacterially expressed pX revealed that the protein possesses hydrolytic activity specific for adenine nucleotides with a Km of approximately 95 microM. This ATPase (dATPase) activity is not DNA-dependent. Mutation analysis revealed that the 88-119 amino-acid region of pX is required for its maximal activity. The putative involvement of (d)ATPase activity in the mechanism of transcription stimulation exerted by pX may be proposed by a certain analogy to the activity of transcription factors which participate in the initiation complex. PMID- 8009851 TI - Activation of RNA polymerase III transcription of human Alu elements by herpes simplex virus. AB - We found that HSV infection of HeLa cells strongly induces RNA polymerase III transcription of endogenous human Alu elements, resulting in the accumulation of high levels of cytoplasmic RNAs initiated from Alu pol III promoters. Induction required viral protein synthesis and occurred during infection with a viral mutant bearing a null mutation in the immediate-early (IE) gene encoding ICP4, suggesting that one or more IE proteins are sufficient for activation. However, mutations in each of the other four IE genes had no effect on activation of Alu expression. We therefore conclude that HSV most likely encodes at least two proteins that are each sufficient to activate Alu transcription and that at least one of these is an IE protein other than ICP4. PMID- 8009852 TI - Immunodetection of rice dwarf phytoreoviral proteins in both insect and plant hosts. AB - Peptides encoded by truncated (S1 and S2) or full-length (S3 to S11) cDNAs of 11 of the 12 rice dwarf phytoreovirus (RDV) genome segments were expressed in a baculovirus vector system. Antibodies raised against each of the expressed peptides were used as probes to detect the authentic proteins encoded by the RDV open reading frame. Polypeptides identified as gene products of S1 to S11 in both RDV-infected rice leaf and leafhopper (Nephotettix cincticeps) homogenates were the P1 minor core (170 kDa), P2 (130 kDa), P3 major core (110 kDa), Pns9 nonstructural (83 kDa), P5 (89 kDa), Pns6 nonstructural (56 kDa), P7 minor core (58 kDa), P8 outercapsid (43 kDA), Pns9 nonstructural (49 kDa), Pns10 nonstructural (35 kDa), and Pns11a nonstructural (23 kDa) proteins. These molecular masses were in accord with those obtained from previous in vitro translation analysis. The locations of P2 and P5 remain to be determined although both of these are assumed to be outer layer proteins. Quantitative detection showed that accumulation (per gram of total proteins) of the virus-coded proteins in rice leaves is much greater (more than 15 times) than that in leafhoppers and that the content of the individual proteins varies within a sample from rice or leafhopper and also varies among different samples. PMID- 8009853 TI - Reiterated DNA fragments in defective genomes of Autographa californica nuclear polyhedrosis virus are competent for AcMNPV-dependent DNA replication. AB - We previously reported on the generation of approximately 50-kb size defective genomes (DGs) which appeared to retain less than 2.2% of the standard Autographa californica nuclear polyhedrosis virus (AcMNPV) DNA between 85.0 and 87.2 MU while the rest of the virus DNA had been largely deleted (Lee and Krell, J. Virol., 66:4339-4347, 1992). To investigate these presumably repeated sequences further, we cloned and analyzed the most abundant hypermolar 1.80-kb Xhol DNA fragment as well as a minor but also supermolar 1.74-kb Xhol fragment of the DGs. These two DNA segments collectively covered 2371-bp of the standard AcMNPV DNA with a 1174-bp overlap around the Xhol site at 85.9 MU. Analysis of DGs by two dimensional gel electrophoresis indicated that the 1.80- and 1.74-kb Xhol fragments (and most other novel Xhol fragments of the DG) were organized as tandem repeats in the DGs. We identified, in the DG population, small supercoiled DNA molecules approximately 1.0- to 8.2-kb (and possibly up to around 50 kb, the size of the major defective DNA species) in size and which contained the same DNA sequence as that of the major 1.80-kb repeat in the DGs. Furthermore, these cloned repeat sequences, represented by pLK1.80 and pLK1.74 showed AcMNPV infection-dependent autonomous replication, suggesting that an origin of DNA replication might reside within the HindIII to EcoRI segment (85.1 to 86.6 MU) of the HindIII-K fragment. PMID- 8009854 TI - Differentiation-specific transcriptional regulation of the hepatitis B virus nucleocapsid gene in human hepatoma cell lines. AB - Transcription from the hepatitis B virus (HBV) nucleocapsid promoter is regulated in a cell-type-specific manner and can be modulated by the HBV enhancer I element. Mutagenesis analysis of the nucleocapsid promoter demonstrated that the two Sp1-binding sites (CpB and CpC) in the minimal promoter were the major determinants of transcriptional activity in the dedifferentiated hepatoma cell line, HepG2.1, and the human cervical carcinoma cell line, HeLa S3. In contrast, binding sites for transcription factors located immediately upstream (CpE) and downstream (CpF) of the two Sp1-binding sites were shown to be important determinants of nucleocapsid promoter activity in the differentiated hepatoma cell lines, Huh7 and HepG2. The role of these elements in the regulation of the nucleocapsid promoter activity correlated with the formation of specific DNA protein complexes between Huh7 and HepG2 nuclear extracts and the CpE and CpF region sequences. Characterization of the influence of the nucleocapsid promoter mutations in the presence or absence of the enhancer I demonstrated that modification of individual transcription factor binding sites does not prevent enhancer-mediated activation of transcription from the nucleocapsid promoter. These results indicate that differentiated-hepatoma-specific transcription factors plus the Sp1 transcription factor interacting with the nucleocapsid promoter and the enhancer I regulatory region contribute to the level of transcription from this HBV promoter. PMID- 8009855 TI - cDNA-derived hypovirus RNA in transformed chestnut blight fungus is spliced and trimmed of vector nucleotides. AB - Unencapsidated double-stranded viral RNAs belonging to the genus Hypovirus attenuate virulence of the chestnut blight fungus, Cryphonectria parasitica. A full-length cDNA clone of hypovirus CHV1-713 double-stranded RNA was recently shown to be infectious when introduced into the C. parasitica genome by DNA mediated transformation. In this study, we show that the viral RNA derived from the chromosomally integrated cDNA copy is trimmed of extraneous vector nucleotide sequences. The cDNA-derived viral RNA was also found to contain a 73-bp deletion located within the 5'-noncoding leader sequence as a result of a pre-mRNA splicing event. Implications of these results are discussed in terms of hypovirus RNA replication and anticipated field studies involving engineered hypovirulent C. parasitica strains. PMID- 8009856 TI - Cloning and sequencing of the spherulin gene, the occlusion body major polypeptide of the Melolontha melolontha entomopoxvirus (MmEPV). AB - In the late stage of infection, virions of the Melolontha melolontha entomopoxvirus (MmEPV) are occluded into cytoplasmic paracrysalline proteinaceous occlusion bodies designated spherules (A. Amargier, C. Vago, G. Meynadier, 1964, Mikroskopie 19, 309-315). We have cloned and sequenced a 4-kpb DNA fragment of the MmEPV genome encompassing the spherule major protein gene named spherulin. The spherulin gene contains an open reading frame able to code for a 942-amino acid (aa) polypeptide (MW 109 kDa), consistent with a size above 100 kDa determined by SDS-PAGE for purified spherulin. The MmEPV spherulin showed more than 40% as homology with the Amsacta moorei EPV (AmEPV) spheroidin and shared homologies with the partially sequenced Choristoneura biennis EPV (CbEPV) spheroidin, indicating that this biologically important polypeptide is well conserved among EPVs infecting phylogenetically as distant groups of insects as lepidoptera and coleoptera. Western blot analyses confirmed the relationships between the three polypeptides. In contrast, no homology was detected between the MmEPV spherulin and EPV fusolins or vertebrate poxvirus A-type inclusion proteins. The 45 bases upstream from the ATG initiation codon of spherulin shared 60% homology with the vaccinia virus late promoters including the highly conserved TAAATG consensus sequence. Furthermore, the 5' extremity of the spherulin mRNA consisted of a poly(A) tract of about 20 nucleotides just upstream from the AUG translational initiation codon. These are characteristic features of vertebrate poxvirus late mRNAs suggesting similar modalities of gene expression for vertebrate and insect poxvirus genomes. PMID- 8009857 TI - Mapping of upstream regulatory elements in the P4 promoter of parvovirus minute virus of mice. AB - The early promoter (P4) of the autonomous parvovirus minute virus of mice (prototype strain) directs the expression of the transcription unit coding for the nonstructural proteins NS1 and NS2. Although proximal promoter elements (GC and TATA boxes) are essential for P4 activity in vivo, additional upstream sequences appear to be required for optimal transcription. Therefore, associations of proteins with the upstream regulatory region of promoter P4 were studied in the rat fibroblast cell line FREJ4 by gel retardation and in vitro as well as in vivo footprinting assays. This led to the identification of at least four distinct upstream elements that interacted with cellular proteins. The functionality of these elements was supported by the reduced level of gene expression driven by corresponding linker-substitutive mutants of promoter P4. PMID- 8009858 TI - HIV-2 EHO isolate has a divergent envelope gene and induces single cell killing by apoptosis. AB - The human immunodeficiency virus type 2 (HIV-2)-related isolate, referred to as HIV-2 EHO, has been isolated from an Ivory Coast patient with acquired immunodeficiency syndrome (AIDS). Infection of CD4 expressing cells with this highly infectious virus mediates a cytopathic effect characterized by single-cell killing as a consequence of apoptosis. Nucleotide sequence analysis of the HIV-2 EHO genome revealed a significant degree of divergence of its envelope gene from that of other known HIV-2 strains. This divergence for the deduced amino acid sequence corresponding to the extracellular envelope glycoprotein was 26 to 30%. These unique genetic and biological properties suggest that the HIV-2 EHO isolate is a distinct prototype in the HIV-2 family. PMID- 8009859 TI - RNA polymerase I-mediated expression of influenza viral RNA molecules. AB - RNA polymerase I transcription has been used for expression of influenza vRNA molecules, with influenza hemagglutinin or other cDNAs precisely inserted between mouse rDNA promoter and terminator sequences. In in vitro studies generation of HA vRNA transcripts in high rates and correct formation of their 5' ends as well as their 3' ends has been achieved for such hybrid DNA templates. For in vivo expression studies, the HA coding region was replaced by chloramphenicol acetyltransferase (CAT), also in vRNA antisense orientation, with both influenza terminal sequences beyond start and stop codons being retained on the resulting transcript. Following transfection with precisely constructed hybrid DNA templates and depending on infection with influenza virus, CAT activity could be demonstrated. Templates resulting in 3' extended vRNA molecules did not give this result. vRNA-CAT molecules were not only recognized by influenza viral RNA polymerase for synthesis of plus strand mRNAs, but also were packaged into progeny virus particles, as shown by CAT activity in infected cells after passaging of virus containing supernatants. PMID- 8009860 TI - Analysis of a type D retroviral capsid gene expressed in ovine pulmonary carcinoma and present in both affected and unaffected sheep genomes. AB - Ovine pulmonary carcinoma is a contagious neoplastic disease of sheep which can be transmitted experimentally with cell-free filtrate. Products homologous to structural proteins of type D and type B retroviruses are expressed in the tumors, but an infectious retrovirus has yet to be isolated. Retroviral RNA was isolated from an affected Peruvian sheep and used as a substrate for reverse transcription. The DNA obtained was subjected to polymerase chain reaction amplification using degenerate primers designed to amino acid sequences shared by the capsid peptides of the viruses that cross-react with the proteins found in the tumor tissues. A retroviral capsid region of type D lineage was isolated that proved to be highly homologous to the jaagsiekte sheep retrovirus isolated from affected sheep in South Africa. This capsid sequence was used to detect the virus in the genomes of sheep with and without ovine pulmonary carcinoma. More than 20 endogenous sequences that hybridized with the probe were found in the sheep examined, and assortment of these could be followed in sheep families. Initial experiments did not show any obvious differences in viral presence in the tumors compared with the background of endogenous viral sequences in unaffected lungs. PMID- 8009861 TI - The Rev protein of visna virus is localized to the nucleus of infected cells. AB - Visna virus is a lentivirus of sheep that is distantly related to the human lentivirus HIV-1. Like other lentiviruses, the genome of visna virus contains multiple small open reading frames that encode viral regulatory proteins. The product of one of these regulatory genes is the visna virus Rev protein, Rev-V. In this report, immunoprecipitation of visna virus-infected cells using a specific anti-Rev-V antibody, generated to a synthetic, carboxyl-terminal peptide of Rev-V, brings down a 22.5-kDa protein identical in size to the protein expressed from a functional Rev-V cDNA clone. Examination of the phosphorylation state of Rev-V indicates that it, unlike the Rev proteins of HIV-1 and CAEV, is not efficiently phosphorylated in infected cells. Cell fractionation and immunofluorescence analysis indicate that, in contrast to a previous report, Rev V is strongly localized to the nucleus and concentrated in nucleoli of visna virus-infected cells. In addition, Rev-V localizes similarly in several different primary cells, in particular macrophages, infected with visna virus. These data indicate that the Rev-V protein is produced during visna virus infection and is localized to the nucleolus of the infected cell. PMID- 8009863 TI - Pseudorabies virus immediate-early regulatory protein IE180 expressed by recombinant baculovirus is functional. AB - IE180, an immediate-early regulatory protein of pseudorabies virus, is required to activate viral early and late genes and is essential for viral growth. We constructed a recombinant baculovirus expressing IE180 in SF21AE insect cells. IE180 expressed by the recombinant migrated on gels as a single band with a molecular weight of 180 kDa and reacted with anti-IE180 peptide serum in Western blotting assay. Immunofluorescence using anti-IE180 peptide antibody demonstrated the accumulation of IE180 in cytoplasm of SF21AE cells infected with the recombinant virus. The IE180 produced in the insect cells was introduced into mammalian Vero cells infected with a PrV mutant with deletion of the IE180 gene by a cell-fusion technique. The growth of the deletion mutant in the fused cells was confirmed by infective assay and immunodetection of the progeny virus. This indicates that the IE180 expressed by the recombinant baculovirus is functional as a transactivator. PMID- 8009862 TI - Regulation of the herpes simplex virus latency-associated transcripts during establishment of latency in sensory neurons in vitro. AB - The temporal appearance of the major latency-associated transcript (LAT) of herpes simplex virus, type-1 (HSV-1) was examined in sensory neuronal cultures during the establishment of either a latent or a lytic infection. Under conditions that result in the establishment of a latent infection, a significant delay in LAT accumulation was observed. The delay in the appearance of LAT was reflected in both a reduced number of LAT-positive neurons detected by in situ hybridizations and by low levels of the major 2-kb LAT detected by Northern blot analysis at early times compared to later in the latent infection. The percentage of LAT-positive neurons shown by in situ hybridizations and the relative abundance of the major LAT by Northern blot analysis increased markedly by 14 days after inoculation with virus. In addition to the major LAT, a spliced 1.5-kb LAT species was detected in Northern blot analysis after establishment of latency in the neuronal cultures, similar to observations in vivo. In contrast to the latent infection, under conditions that produced lytic infections in the neuronal cultures, LAT and HSV-1-specific antigens were detected in the majority of neurons 24 hr after inoculation with virus. These results indicate that LAT expression during the establishment of latency is regulated differently than during the lytic infection: LAT expression appears to be inhibited initially during the establishment of latency, whereas LAT is readily expressed during the lytic infection. PMID- 8009864 TI - Role of N-linked glycosylation in the activity of the Friend murine leukemia virus SU protein receptor-binding domain. AB - The 243 N-terminal residues of Friend Murine Leukemia Virus envelope glycoprotein (SU) fold into a structurally and functionally autonomous domain which contains the determinants for binding to the ecotropic virus receptor. The two N-linked glycosylation sites present in this N-terminal portion of the viral SU were removed by site-directed mutagenesis without disturbing its biosynthesis and incorporation into infectious virions. A truncated version of the mutant protein which included only the N-terminal domain was poorly transported but still able to interact with the receptor. Interference assays indicated that the interaction between the mutated protein and the virus receptor was weaker. We conclude that the elimination of N-linked oligosaccharide chains in the envelope N-terminal domain do not prevent receptor interaction but results in subtle conformational changes that may alter recognition and binding. PMID- 8009865 TI - Biological and molecular characteristics of human herpesvirus 7: in vitro growth optimization and development of a syncytia inhibition test. AB - Two isolates of human herpesvirus 7 (HHV-7) were recovered from phytohemagglutinin-activated peripheral blood mononuclear cells of a patient with chronic fatigue syndrome and of a healthy blood donor. A genetic polymorphism between the two isolates was detected by Southern blot analysis using a novel HHV 7 genomic clone (pVL8) as a probe. We developed optimized conditions for the in vitro propagation of HHV-7 by using enriched populations of activated CD4+ T lymphocytes derived from normal peripheral blood, resulting in the production of high-titered extracellular virus (> 10(6) cell culture infectious doses/ml). Bona fide syncytia formation was documented both in normal CD4+ T lymphocytes and in the Sup-T1 CD4+ T-cell line following infection with high-titered HHV-7. To identify neutralizing antibodies to HHV-7, a syncytia-inhibition test was developed. Variable titers of syncytia-neutralizing antibodies were detected in all the human sera tested, thus confirming the high prevalence of HHV-7 in the human population. PMID- 8009866 TI - Induction of developmentally programmed cell death and activation of HIV by sodium butyrate. AB - Apoptosis is an important regulatory process during normal development and maturation. We find that the proliferation-arresting and differentiation-inducing compound sodium n-butyrate (NaB) triggers a marked host chromatin degradation. This apoptotic process is independent of, but commensurate with, a rapid increase in viral mRNA synthesis and subsequent release of HIV-1 virus in transformed human cell lines harboring tat- (HLM1) or tat+ (U1, ACH-2) dormant HIV-1 proviruses. This compound stimulates a reversible accumulation of the characteristic viral mRNAs at a much faster rate than two other DNA degradation inducers such as tumor necrosis factor-alpha and phorbol 12-myristate 13-acetate. The transcriptional activator butyrate analogue, alpha-amino-n-butyrate, failed to cause similar phenotypic changes. These results suggest that common regulatory signals may be involved in activation of apoptosis genes and latent provirus by NaB. PMID- 8009867 TI - A truncated HTLV-I envelope protein, lacking the hydrophobic membrane anchor domain, is associated with cellular membranes and virions. AB - The HTLV-I producer cell line C10/MJ2 does not induce syncytium formation with HTLV-I receptor expressing cells. Here we show that this cell line produces a truncated envelope protein, which, because of a premature stop codon, lacks the hydrophobic membrane anchor domain of the transmembrane protein (TM). Despite lacking a membrane anchor this envelope protein is expressed on the cell surface and associated with released virions. However, its incorporation into virions seems less efficient than that of a full-length envelope glycoprotein and some of its released into the cell culture supernatant as soluble surface glycoprotein (SU)-TM complexes. Small amounts of such a truncated envelope glycoprotein were also found in the fusion-competent HTLV-I producer cell line MT2. Premature truncation of HTLV-I envelope proteins in producer cell lines may result from in vitro selection for a less fusogenic phenotype. The association of truncated HTLV I envelope proteins with virions and cell surfaces may reflect interactions between the SU domain and cellular membranes, possibly with the cellular receptor for HTLV-I. PMID- 8009868 TI - The envelopes of two ecotropic murine leukemia viruses display distinct efficiencies in retroviral vaccination by interference. AB - In cell cultures infected with a retrovirus, the expression of the viral envelope interferes with superinfection by retroviruses which recognize the same receptor. We have previously demonstrated that vaccination of susceptible strains of mice (of the Mus musculus species) with the attenuated ecotropic Friend murine leukemia virus (F-MuLV) B3 efficiently protects against the early hemolytic anemia and the erythroleukemia induced by a challenge with the virulent F-MuLV 57 through a similar in vivo mechanism of interference to superinfection (A. Corbin and M. Sitbon, J. Virol. 67, 5146-5152, 1993). Vaccination with the heterologous ecotropic Moloney-MuLV (M-MuLV) efficiently protects against the early hemolytic anemia but has a weak protective effect on the F-MuLV 57-induced erythroleukemia. Furthermore, vaccination with the attenuated F-MuLV B3 had only a transient protective effect on M-MuLV-induced thymomas. These different efficiencies of F- and M-MuLV to confer protection in this model of vaccination by interference were mostly due to envelope sequences, indicative of distinct in vivo interference properties of the two ecotropic envelopes. PMID- 8009869 TI - Production of host shutoff-defective mutants of herpes simplex virus type 1 by inactivation of the UL13 gene. AB - Two mutants of HSV-1(SC16) carrying disrupted UL13 genes have been generated independently by recombination of wild-type genomic DNA with a plasmid-cloned copy of the UL13 gene containing multiple stop codons. The two mutants were shown to be deficient in UL13 gene expression by Western blotting of infected cells. A revertant virus, in which UL13 expression was restored to a near-normal level, was generated by recombination of one of the UL13-negative mutants with a plasmid carrying the wild-type UL13 gene. The replication of the two UL13-negative viruses in cell culture was somewhat reduced compared to their wild-type parent, and the viruses were unable to produce shutoff of host protein synthesis. The replication of the revertant virus was intermediate between that of the UL13 negative and wild-type viruses, as was its ability to produce host shutoff. Cells infected with the UL13-negative mutants were shown to contain much lower levels than normal of the UL41 gene product, which is known to be required for virion host shutoff. However, there was no significant difference between levels of the UL41 gene product in wild-type and mutant virions. The UL13-negative viruses exhibited different patterns of protein phosphorylation from wild-type virus when infected cells were metabolically labeled with [32P]-orthophosphate and when lysates of infected cells and of virions were subjected to in vitro phosphorylation. However, the UL41 gene product could still be phosphorylated in lysates of UL13-negative virions. We conclude that the UL13 gene is necessary to produce the virion host shutoff effect, but it seems unlikely that the role of UL13 is simply to activate the UL41 gene product by phosphorylation. PMID- 8009870 TI - The Health Care Quality Improvement Program: the WVMI returns to its founding mission. AB - The Health Care Financing Administration (HCFA) has launched and ambitious new program for Peer Review Organizations (PROs) called the Health Care Quality Improvement Program (HCQIP). The goal of HCQIP is to improve the quality of care for all Medicare beneficiaries through cooperative interaction between PROs, providers, and physicians. The West Virginia Medical Institute, which serves as the PRO for West Virginia and Delaware, has recently begun to implement the changes required by HCQIP. This article explains the various approaches WVMI will use to achieve the health care improvement goals set forth by HCFA. PMID- 8009871 TI - Idiopathic long q-t syndrome: brief case report and discussion. AB - Idiopathic long q-t syndrome (LQTS) is an infrequently occurring familial disorder in which affected family members have an abnormally prolonged q-tc interval with syncope, ventricular arrythmias and sudden death. In this article, we present the case of a 54-year-old female admitted for syncope, who was on no medications except for insulin. Her electrocardiogram on admission had prolonged q-tc interval (0.50 ms.). She had repeated episodes of torsades de pointes during her hospitalization, which were later controlled by beta-blockers. Electrocardiograms of her mother and daughter showed asymptomatic prolonged q-tc interval. This syndrome has an autosomal dominant pattern of transmission and it was first described by Romano and Ward in a patient with normal hearing. Our case is unusual because this condition presented so late in life. PMID- 8009872 TI - Sporadic multiple lipomatosis: a case report and review of the literature. AB - The finding of multiple lipomas, or lipomatosis, can be a marker for several clinical or familial syndromes. Familial multiple lipomatosis is a benign hereditary disorder of adipose regulation associated with hyperlipidemia. Multiple symmetric lipomatosis involves the local infiltration of adipose tissue of the neck, upper torso and mediastinum. This condition is often found in alcoholics and has been associated with diabetes mellitus. An afflicted patient's family history is important both to reveal occult pathology and to help determine the disease's prevalence in the population. In this article, we report the case of a patient with sporadic multiple lipomatosis and provide a brief review of the literature. PMID- 8009873 TI - Managed care. PMID- 8009874 TI - Nursing beyond the year 2000. Report of a WHO Study Group. PMID- 8009875 TI - Health care, rights and the Wizard of Oz. PMID- 8009876 TI - WMJ article on carpal tunnel release inspires discussion. PMID- 8009877 TI - Experience with macroscopic vasectomy reversal at the Medical College of Wisconsin. AB - Thirty-two men underwent vasectomy reversal using loupe magnification at the Medical College of Wisconsin between 1984 and 1991. Semen analysis and pregnancy data were available for 27 of them, and sperm were present in the ejaculate of 24, representing a patency rate of 89%. Pregnancy was established by 11, for a pregnancy rate of 41%. These results suggest that vasovasostomy using loupe magnification provides acceptable rates of patency and pregnancy, although the pregnancy rate appears to be somewhat lower than that reported for microsurgical repair. The lower cost of macroscopic vasectomy reversal may outweigh the potential statistical advantages for some couples. PMID- 8009879 TI - Preventable causes of death in Wisconsin. PMID- 8009878 TI - The surgeon, needle-sticks, and HIV. AB - This review article looks at needle-stick injuries and human immunodeficiency virus (HIV) conversion from a surgical perspective. Is the risk high or low? That depends on: the rate of HIV in your patients (varies by region); the likelihood of getting injured (varies by specialty); and the HIV conversion rate from the injury (an elusive number that varies with the injury). The current literature was reviewed to see how risky surgery currently is. This leads us to speculate on the HIV risks of the near future. PMID- 8009880 TI - AMA candidate Tim Flaherty, MD, tackles issues facing physicians. Interview by Shari Hamilton. PMID- 8009881 TI - SMS commission updates guidelines on terminal care in long-term care facilities and at home. PMID- 8009882 TI - On the reactions of the carbapenem, meropenem, in the soluble fraction of rat kidney. AB - 1. When meropenem (I) is incubated with the soluble fraction of rat kidney or its ultrafiltrate the carbapenem disappears at a rate of 50 nmol/min per g of kidney at pH 8.4 and 37 degrees C. 2. In both cases the kinetics are inconsistent with the reaction being enzymic and the product has been shown to be a thiol. 3. The same reaction occurs in similar preparations from the kidney of several other mammalian species. 4. The reaction of meropenem with thiols has been investigated: only those having a vicinal amino group react rapidly. 5. The product of the reaction with cysteine has been characterized as the amide(III) of the latter with meropenoic acid (II), the carboxylic acid formed by the hydrolysis of the beta-lactam ring of meropenem. 6. It is postulated that the destruction of meropenem in the soluble fraction of rat kidney occurs by the non enzymic reaction of the carbapenem with endogenous cysteine or related thiols. 7. There is no evidence that this reaction can occur in vivo but it should be considered in the future design of carbapenems. PMID- 8009883 TI - Synthesis and structural elucidation of biliary excreted thioether derivatives of mitoxantrone. AB - 1. Hplc-MS coupling has been used for the identification of thioether derivatives of the anticancer agent mitoxantrone in the bile of pig. 2. Three biologically relevant new thioether derivatives of mitoxantrone have been synthesized by a horseradish peroxidase-catalysed reaction. 3. The thioether derivatives have been characterized by means of ion-spray tandem mass spectrometry and nmr spectrometry including two-dimensional techniques. 4. The carbon-sulphur bond formation takes place at the hydroquinone moiety of the anthraquinone skeleton pointing to the importance of a tautomeric equilibrium between different species of the oxidized drug. 5. The occurrence of the synthesized compounds in biological systems suggests a metabolic pathway that may be relevant for the cytotoxicity of mitoxantrone (oxidative activation). PMID- 8009884 TI - Effect of E-5110, a novel non-steroidal anti-inflammatory drug, on trimethadione metabolism as an indicator of hepatic drug-oxidizing capacity in beagle dog. AB - 1. We examined the effects of N-methoxy-3-(3,5-di-tert-butyl-4- hydroxybenzylidene pyrrolidin-2-one (E-5110), a novel non-steroidal anti inflammatory drug, on the pharmacokinetics of trimethadione (TMO) and characterized the P450 isozymes involved in the metabolism of TMO in beagle dog. 2. In the E-5110-treated dog (50 mg/kg/day for 7 days: oral) the plasma half-life (t1/2) and the area under the curve (AUC) of TMO (4 mg/kg, i.v.) in vivo were decreased, and total body clearance (CL) was increased; the apparent volume of distribution (Vd) was relatively unchanged. 3. Contents of P450 and b5, and the activity of p-nitroanisole O-demethylase and benzphetamine N-demethylase in vitro were significantly increased compared with controls by repeated E-5110 treatment in dog. 4. Contents of CYP2B and 3A were increased by E-5110 pretreatment in dog. 5. TMO N-demethylation was inhibited by the anti-CYP2B and 3A IgG fractions in liver microsomes obtained from the E-5110-treated dog. 6. Results of both the in vivo and in vitro studies of the effects of E-5110 treatment in dog on TMO indicate that these effects may be attributed to the induction of CYP2B and 3A. PMID- 8009885 TI - Urinary and biliary metabolites of pyrene in rainbow trout (Oncorhynchus mykiss). AB - 1. Pyrene was administered i.p. as a single dose to trout (Oncorhynchus mykiss). Urine was collected continuously for 3 days and bile sampled at the end of this period. Pyrene metabolites in these biological fluids were identified by 1H-nmr spectrometry, glc-ms and hplc-ms. 2. 1-Hydroxypyrene was the major oxidation metabolite in the urine and bile. Small amounts of 1,6-dihydroxypyrene and a putative 1,8-dihydroxypyrene metabolite also were detected. Unchanged pyrene was not found in any of these biological fluids. 3. Both free and conjugated metabolites of pyrene were found in the bile and urine. The majority of the pyrene metabolites in the bile were conjugated with glucuronic acid or sulphate. PMID- 8009886 TI - 7-Ethoxycoumarin O-deethylase kinetics in isolated rat, dog and human hepatocyte suspensions. AB - 1. A comparative study of the kinetics of the O-deethylation of 7-ethoxycoumarin has been carried out in freshly isolated rat, dog and human hepatocytes. 2. Biphasic kinetics were observed for all three species with apparent Km and Vmax values of 11.5, 2.2 and 3.9 microM and 0.30, 0.21, 0.007 nmol/min/10(6) cells from rat, dog and man, respectively, for the high affinity-low capacity component, and 560, 40, 470 microM and 1.52, 0.74, 0.057 nmol/min/10(6) cells, respectively, for the low affinity-high capacity component. 3. These observed kinetic parameters in hepatocytes from rat and man were similar to published values for microsomes for the same two species. 4. Values for intrinsic clearance of 7-ethoxycoumarin for the three species calculated from the Km and Vmax data were 152, 631 and 6 ml/min/kg for rat, dog and human hepatocytes, respectively. These intrinsic clearance values predict that 7-ethoxycoumarin would be subject to a high hepatic clearance in rat and dog, and low hepatic clearance in man. These values are supported by published data on rat which show that 7 ethoxycoumarin is subject to high clearance. PMID- 8009887 TI - Importance of metabolic stability and hepatic distribution to the pharmacokinetic profile of amlodipine. AB - 1. In an isolated perfused rat liver (IPRL) model, the extensive hepatic uptake and subsequent slow redistribution of amlodipine into the perfusate have been demonstrated. The apparent liver volume for amlodipine was 920 ml compared with 38ml for nitrendipine. 2. Metabolism is the major clearance mechanism of amlodipine and nitrendipine in animals and man. In the IPRL, the intrinsic (metabolic) clearance and first-pass extraction values for amlodipine are similar to those of nitrendipine. This is in contrast with in vitro metabolic stability data in rat liver microsomes which indicate about 40-fold greater metabolic stability for amlodipine. 3. The discrepancy between relative clearance rates for the two preparations may be explained by consideration of the hepatic volume of the two compounds, with the higher liver volume of amlodipine amplifying the whole organ clearance. PMID- 8009888 TI - Dissociation of covalent protein adduct formation from oxidative injury in cultured hepatocytes exposed to cocaine. AB - 1. The relationship between the oxidative and the alkylating properties of cocaine was investigated in primary cultures of hepatocytes derived from phenobarbital-pretreated rats. 2. The cytotoxic effects (LDH release) of 300 microM cocaine were preceded by depletion of intracellular glutathione (GSH) and concomitant increases of oxidized glutathione (GSSG). Furthermore, exposure to [3H]-cocaine was associated with the formation of covalent protein adducts which plateaued between 2 and 7 h and which remained stable for at least 24 h. 3. The addition of the thiol-reducing agent dithiothreitol (DTT, 0.5 mM) protected against cocaine-induced LDH release without altering the time course and extent of cocaine covalent protein adduct formation. Similarly, when DTT was added after short-term exposure to cocaine in Krebs-Henseleit buffer, the loss of viability could be prevented, indicating that alterations in the thiol redox equilibrium, and not covalent protein adduct formation per se, may be crucial for the development of hepatocyte injury. In contrast, high concentrations (2.5-5.0 mM) of DTT inhibited both cocaine bioactivation and covalent binding and thus protected through prealkylative mechanisms. 4. Data demonstrate that cocaine induced acute lethal hepatocyte injury was mediated by non-alkylative mechanisms, and that covalent adduct formation could be clearly dissociated from the consequences of oxidative stress that lead to cell killing. PMID- 8009889 TI - Bromobenzene detoxification in the human liver-derived HepG2 cell line. AB - 1. The applicability of the human hepatoma cell line, HepG2, as a cell culture model for studying xenobiotic liver toxicity has been investigated using the well characterized hepatotoxic chemical, bromobenzene. 2. Bromobenzene caused a concentration- (0-10 mM) and time-dependent (0-180 min) decrease in HepG2 cell viability. The degree of toxicity was dependent upon the culture medium composition and the state of cell growth. Toxicity in Modified Earle's and Williams' E Media was maximal at 7 days growth compared with 3 and 10 days, and was greater in Williams' than in Earle's medium. Toxicity in Dulbecco's medium was apparent only at 10 days growth and was less than the maximum toxicity in the other media. 3. Bromobenzene was detoxified by epoxide hydrase. The question of metabolic activation by P450 remained unresolved, but any involvement of P450 was by forms not inhibited by ketoconazole. 4. The mechanism of bromobenzene toxicity did not appear to involve lipid peroxidation, depletion of reduced glutathione, calcium-mediated proteolysis or metabolic activation by prostaglandin synthetase, but may have involved direct solvent-induced cell damage. 5. This study demonstrates the potential usefulness of HepG2 cells in toxicity testing and highlights the importance of standardizing culture conditions. PMID- 8009891 TI - Expression and localization of human papillomavirus type 16 E6 and E7 open reading frame proteins in human epidermal keratinocyte. AB - Over 60 different types of human papillomavirus (HPV) have been identified, and they are classified into high and low risk groups based on the risk for malignant progression of HPV associated lesions. HPVs belonging to a high risk group have been shown to express two major transforming proteins, E6 and E7. With respect to the transforming activity of these proteins, many investigators have reported the location of these proteins in the cell, but their results are still controversial. In the present study, HPV type 16 E6 or E7 open reading frame (ORF) proteins were expressed and localized in human epidermal keratinocytes (RHEK-1) using the vaccinia virus as an expression vector. Immunofluorescence detection using monoclonal antibodies against E6 or E7 ORF proteins revealed that E6 or E7 proteins of HPV type 16 were located in the cytoplasm of RHEK-1 cells. These results suggest that E6 and E7 proteins bind to the tumor suppressor counterparts, thereby preventing transport of these proteins into the nucleus. These antioncogene products that fail to be rapidly transported out of the cytosol may be degraded by certain proteases such as the ubiquitin dependent system. In this way, the precise function of antioncogene products in the regulation of cell growth could be destroyed, and abnormal cell growth could occur. PMID- 8009890 TI - Protection by ascorbic acid against oxidative injury of isolated hepatocytes. AB - 1. The ability of ascorbic acid to protect from prooxidant-induced toxic injury was investigated in isolated, intact rat hepatocytes, whose ascorbic acid content had been restored by means of exogenous supplementation. 2. Ascorbate supplemented and ascorbate-non-supplemented cells in suspension were treated with a series of different prooxidants (allyl alcohol, diethyl maleate, carbon tetrachloride, menadione), and the development of lipid peroxidation and cell injury was evaluated. 3. With allyl alcohol and diethyl maleate, ascorbic acid was able to protect cells from both lipid peroxidation and cell injury. The same protection was offered by ascorbate also in hepatocytes obtained from vitamin E deficient animals. 4. With carbon tetrachloride, ascorbate supplementation did not affect the initial steps of lipid peroxidation, but nevertheless provided a marked protection against lipid peroxidation and cell injury at later times of incubation. The protection was unaffected by the vitamin E content of cells. 5. With menadione, a toxin which does not induce lipid peroxidation, ascorbic acid did not protect cells against injury. 6. It is concluded that ascorbic acid can act as an efficient antioxidant in isolated rat liver cells, with protection against cell injury. The antioxidant effect appears primarily to involve membrane lipids, and can be independent from the cellular content of vitamin E, thus suggesting that ascorbic acid can play a direct and independent role in the intact cell, in addition to its synergistic interaction with vitamin E described in other models. PMID- 8009893 TI - Spigelian hernia in children--report of two cases and review of the literature. AB - Two children with spigelian hernias are presented in this report. The etiopathogenesis and surgical anatomy of these rare hernias were discussed. Our cases are the fourth and fifth cases of spigelian hernia (SH) in patients under 2 years of age. Surgical intervention is indicated in all cases of SH because of the danger of strangulation of the bowel. PMID- 8009892 TI - Fatty acids directly increase the activity of Ca(2+)-activated K+ channels in rabbit coronary smooth muscle cells. AB - The large conductance Ca2+ activated K+ channel (BK channel) has been considered to play an important role in the excitability and contractility of vascular smooth muscle cells. Activation of the BK channel causes the hyperpolarization and relaxation of vascular smooth muscle cells. It has been reported that fatty acids can affect the BK channel activity and its concentration is increased significantly during myocardial ischemia. These reports suggest that fatty acids may contribute to the ischemic coronary vasodilation by increasing the BK channel activity. However, the underlying mechanism of fatty acid-induced activation of the BK channel is still uncertain. In the present study, we measured the effect of fatty acids on the BK channel activity in rabbit coronary smooth muscle cells by using patch clamp method and also examined its underlying mechanism. Arachidonic acid (AA) dissolved in DMSO activated the BK channel in a dose dependent manner (from 0.5 to 10 microM), and DMSO (0.1%) alone had no effect on the activity of the BK channel. Arachidonic acid activated BK channels in both cell-attached and inside-out patches, but the onset and recovery of this effect were slower in the cell-attached patch configuration. The BK channel activity was also increased by other fatty acids, including myristic acid, linoleic acid, palmitoleic acid and palmitic acid. Long chain fatty acids were more effective than short chain fatty acids (myristic acid), and there was no statistical difference between the effect of saturated (palmitic acid) and unsaturated fatty acids (palmitoleic acid) on the BK channel activity. The concentration of Ca2+ and Mg2+ in the bathing solution had no appreciable effects on the AA-induced increase of BK channel activity. From the above results, it may be concluded that fatty acids directly increase the BK channel activity and may contribute to the ischemic coronary vasodilatation in rabbit coronary smooth muscle cells. PMID- 8009894 TI - Induction of hepatic ATP-citrate lyase by insulin in diabetic rat--effects of insulin on the contents of enzyme and its mRNA in cytosol, and the transcriptional activity in nuclei. AB - The effects of insulin on ATP-citrate lyase, its mRNA in cytosol, and the transcriptional activity in nuclei of diabetic rat liver were studied. Experimental diabetes was induced by an intraperitoneal injection of streptozotocin, and livers were removed from rats at 0, 1, 3, 6, 16, and 72 hours after the administration of insulin. ATP-citrate lyase began to increase at 16 hours, and continuously increased until 72 hours. The amount of mRNA encoding ATP citrate lyase increased abruptly at 16 hours, then decreased to near basal level in 72 hours. No change in the transcription rate was observed until 3 hours after insulin administration. However, the activity increased 4-fold at 6 hours and 7 fold at 16 hours, 16-fold at 6 hours and 28-fold at 16 hours when pGACL1 and pGACL2 were used as probes, respectively, preceding the increase in the amounts of mRNA and the enzyme. It is suggested that the increase in the amount of ATP citrate lyase by insulin is primarily due to the increase in the transcriptional activity of the gene in nuclei, which results in the subsequent increase in the amount of mRNA for the biosynthesis of ATP-citrate lyase in cytosol. PMID- 8009896 TI - Serodiagnosis of human sparganosis by a monoclonal antibody-based competition ELISA. AB - Competition ELISA test using sparganum specific monoclonal antibodies (Mab) was investigated to improve the diagnostic specificity of sparganosis. By cell fusion, one hybridoma clone secreting anti-sparganum specific Mab was selected (Sp-20), which reacted on bands of 32 kDa and 38 kDa. Sp-20 reacted on calcium corpuscles on IFA. By micro-ELISA, 16 of 17 sparganosis cases (95%) were found positive, but 1 of 18 clonorchiasis cases (5%), 4 of 16 cysticercosis cases (25%) and 2 of 16 normal controls (11%) showed false positive reactions. On the other hand, by competition ELISA using a sparganum specific Mab (Sp-20), 16 out of 17 (95%) of sparganosis cases were found positive, but 2 of 18 clonorchiasis cases (10%), 2 of 16 cysticercosis cases (12%), 3 of 16 paragonimiasis cases (18%) and 1 of 16 normal controls (6%) showed false positive reactions. PMID- 8009895 TI - Flow cytometric analysis of DNA ploidy in childhood rhabdomyosarcoma. AB - Flow cytometric DNA analysis was performed on 17 rhabdomyosarcomas in conjunction with a histopathological review to determine the usefulness of this technique to predict the biologic behavior of the tumor and to establish the characteristic ploidy pattern of rhabdomyosarcoma compared to other small round cell tumors occurring in childhood. Aneuploidy including near-tetraploidy is the most common ploidy pattern encountered, followed by multiploidy and diploidy, and the presence of multiploidy in this tumor is useful for differentiating rhabdomyosarcoma from other kinds of small round cell tumors in which there are rare previous reports on occurrence of multiploidy. Even though there is no significant correlation between ploidy pattern and histologic type of rhabdomyosarcoma, patients with multiploid tumors or aneuploid tumors with a DNA index of 1.10-1.80 tend to have a high risk of treatment failure. Therefore, the ploidy pattern seems to be useful for predicting the patient's survival in concert with other variables. PMID- 8009897 TI - Intra-carotid thrombolytic therapy in acute ischemic stroke of carotid arterial territory. AB - Intra-carotid urokinase (UK) infusion in 20 patients with acute internal carotid artery (ICA) territorial ischemic stroke achieved immediate recanalization in 45% and the clinical outcome in patients with recanalization was superior to that of patients without recanalization. The procedure was most effective in patients with smaller arterial occlusions: 7 of 10 patients with MCA branch occlusions (M2 to M4) achieved recanalization compared to only 2 of 10 with distal ICA or M1 occlusions, which should be an important issue for the critical evaluation of the efficacy of thrombolytic therapy (TT). Hemorrhagic transformation was observed in 9 patients on CT scan; petechial hemorrhage in 5 and intraparenchymal hematoma formation in 4. Among 4 patients with hematoma formation, clinical deterioration was seen in 3 cases and the angiography at the immediate end of the UK infusion showed recanalization in only one patient. The average dose of UK in patients with parenchymal hematoma formation was higher than that of patients without hemorrhagic transformation (123.3 x 10(4) units vs 101 x 10(4) units). The administration of a large dose of UK, probably more than 100 x 10(4) units, and the absence of immediate recanalization seemed to increase the risk of parenchymal hematoma formation. Despite the effort of investigators, the in hospital time delay for the TT was significant which was mainly related to the time consuming preparation for angiography especially during night. A more effective system for the earlier intervention of acute ischemic stroke needs to be developed. PMID- 8009899 TI - In vitro pressure drop comparison between two mechanical valve prostheses. AB - An hemodynamic evaluation of two mechanical heart valves is presented. A tilting disc valve and a bileaflet valve were incorporated in a mock circulatory system which consists of a closed flow loop with a pneumatically driven flexible diaphragm to simulate the physiologic pulsatile flow. Comparisons between the valves were made on the aortic pressure, ventricular pressure, as well as mean pressure gradient at a systolic duration of 45% and a heart rate of 90 beats per minute. The results showed that the tilting disc valve has higher ventricular pressure and mean pressure gradient than that of the bileaflet valve. This indicates that the tilting disc valve has higher transvalvular flow resistance and energy loss than that of the bileaflet valve. From this study it is demonstrated that the mock circulatory system can be a very useful device to evaluate the prosthetic heart valves in vitro. PMID- 8009898 TI - The mechanism of antiproliferative effect of desferrioxamine on human hepatoma cell lines. AB - We investigated the effect of desferrioxamine (DFO), an iron chelator, on the DNA synthesis and the cell cycle of cultured hepatoma cells. Using Hep 3B cells as the hepatoma cell lines, DNA synthesis was measured by [3H] thymidine incorporation, and the cell cycle analysis was performed by flow cytometry including bivariate DNA/BrdU analysis. [3H] thymidine uptake was decreased by DFO in a dose dependent manner. The proportion of S phase cells increased and that of G0/G1 phase cells decreased after the addition of DFO in the culture media in a dose dependent manner up to 20 micrograms/ml of DFO. The S phase duration of the exponentially proliferating Hep 3B cells was 9.9 hours when cultured without DFO, but it was markedly prolonged (54.1 hours) after the addition of 20 micrograms/ml of DFO. After removal of DFO from the culture media following 24 hours of incubation with 20 micrograms/ml of DFO, a sequential increase from early through mid and late-S to G2/M phase was observed. In conclusion, the antiproliferative effect of DFO on cultured human hepatoma cell lines was caused by the inhibition of DNA synthesis which was related to a block in the early-mid S interface or mid S phase of the cell cycle. PMID- 8009900 TI - Adaptive response to ionizing radiation induced by low dose of gamma ray in human hepatoma cell lines. AB - When cells are exposed to a low dose of a mutagenic or clastogenic agent, they often become less sensitive to the effects of a higher dose administered subsequently. Such adaptive responses were first described in Escherichia coli. Studies on mammalian cells have been limited to human lymphocytes exposed to low doses of an alkylating agent. In this study, the adaptive response to 1 cGy of gamma rays was investigated in human tumor cells using two human hepatoma cell lines, Hep G2 and Hep 3B. Experiments were carried out by delivering 1 cGy followed by 50 cGy of gamma radiation and chromatid breaks were scored as an endpoint. The results of this study indicate that prior exposure to 1 cGy of gamma rays reduces the number of chromatid breaks induced by subsequent higher doses (50 cGy). The time necessary for the expression of the adaptive response was determined by varying the time interval between the two doses from 1 hour to 72 hours. In G2 chromatids, the adaptive response was observed both at short time intervals, as early as 1 hour, and at long time intervals. In S chromatids, however, the adaptive response was shown only at long time intervals. When 3 aminobenzamide, an inhibitor of poly (ADP-ribose) polymerase, was added after 50 cGy, adaptive responses were abolished in all the experimental groups. Therefore, it is suggested that the adaptive response can be observed in human hepatoma cell lines, which is first documented through this study.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8009901 TI - Mechanics of caloric stimulation in a case with a plug in the horizontal semicircular canal. AB - Horizontal eye movements were recorded by electronystagmography in a subject with a plug of granulation tissue in the unilateral horizontal semicircular canal by the room temperature air caloric stimulation. Stimuli were sequentially presented to both ears with the subject supine and prone, keeping the horizontal canal vertical. Caloric stimuli presented to the unplugged ear resulted in a vestibular nystagmus whose slow phase eye velocity (SPEV) was always directed toward the stimulated side when the subject was supine and toward the opposite side when he was prone. In contrast, calorics presented to the horizontal canal plugged ear showed that SPEV was always directed toward the stimulated side, irrespective of whether the subject was supine or prone. Results were consistent with consensus that the caloric responses noted in the horizontal canal plugged ear reflected horizontal canal afferent activity which may correspond to direct effect of temperature on end organs or afferents. The findings imply that a caloric mechanism exists which is independent of the conventionally accepted one involving concection currents within the canal. PMID- 8009903 TI - Volvulus of the splenic flexure of the colon. AB - The definition of volvulus is an axial twist of a portion of the gastrointestinal tract along its mesentery. The involved bowel is obstructed partially or completely with a variable degree of arterial and venous occlusion. The colon is the most common site for volvulus. The splenic flexure is the least common site of colonic volvulus. We experienced a case of the volvulus of the splenic flexure. It will be the 30th case of the volvulus involving the splenic flexure in the English literature, to our knowledge. A 30-year-old woman was admitted due to abdominal pain and distention with vomiting. An emergency barium study revealed characteristic "bird beak" sign. Surgery was performed resecting the involved colon of splenic flexure. The result was excellent. PMID- 8009902 TI - GM-CSF and low-dose araC treatment of AML in prolonged hypoplasia with residual leukemic cells after induction chemotherapy. AB - We describe a case with acute myelogenous leukemia (AML; M2) who developed prolonged marrow hypoplasia with residual leukemic blasts and recurrent infections after induction chemotherapy. He was treated successfully with a sequential treatment of recombinant human granulocyte-macrophage colony stimulating factor (rhGM-CSF) and low-dose cytosine arabinoside (LD AraC). To the best of our knowledge this is the first reported case of a successful treatment of a patient with AML, who showed prolonged markedly hypocellular bone marrow with significant residual leukemic cells after induction chemotherapy, with a sequential treatment of GM-CSF and LD AraC. PMID- 8009904 TI - [The physiology of fishes]. PMID- 8009905 TI - [The role of the Scientific Council on the Physiological Sciences in the scientific and organizational activities of the Division of Physiology of the Russian Academy of Sciences]. PMID- 8009907 TI - [The physiology of higher nervous activity]. PMID- 8009906 TI - [General physiology and the physiology of the cell]. PMID- 8009908 TI - [Neurophysiology]. PMID- 8009909 TI - [The physiology of the sensory systems]. PMID- 8009910 TI - [The physiology of the vegetative (autonomic) nervous system]. PMID- 8009911 TI - [The physiology of the endocrine system]. PMID- 8009912 TI - [The Scientific Council on the Physiological Sciences of the Russian Academy of Sciences: its structure and goals]. PMID- 8009913 TI - [The physiology of blood circulation]. PMID- 8009914 TI - [The physiology of respiration]. PMID- 8009915 TI - [The physiology of digestion]. PMID- 8009916 TI - [The physiology of the blood system and of the immune system]. PMID- 8009917 TI - [The physiology of the motor system]. PMID- 8009918 TI - [Ecological physiology]. PMID- 8009919 TI - [The physiology of extreme states]. PMID- 8009920 TI - Cooperative care in dentistry. PMID- 8009922 TI - Orthodontics in the mixed dentition. PMID- 8009921 TI - Collaborative Care. PMID- 8009923 TI - [Noninvasive methods for diagnosing brain involvement in systemic lupus erythematosus]. PMID- 8009924 TI - [The pharmacological properties of calcium channel blockers and the outlook for their use in psychiatry and neurology]. PMID- 8009925 TI - [The weakening of the inhibition of the H-reflex in patients who have had a stroke and its relation to spasticity of the skeletal musculature]. AB - Inhibition of the soleus H-reflex was studied in hemiparetic postapoplectic patients and in control group of patients without motor disorders. The depression of H-reflex was caused by stimulation of ipsilateral peroneal nerve and presented in two successive waves (D1 and D2). The former of them corresponds to presynaptic inhibition. The size of both waves of inhibition was reduced in postapoplectic patients according to the degree of their muscle spasticity. PMID- 8009926 TI - [The early and subclinical forms of cerebrovascular pathology in patients with chronic ischemic heart disease]. AB - The results of a cardioneurological follow-up enabled the authors to develop the principles of the angioneurological evaluation of patients with chronic coronary heart disease (CCHD). The survey covered 118 CCHD males aged 40-59 of functional class I and II. A differential complex of tests involving neuropathological and neuropsychological examinations, rheoencephalography with pharmacological and bicycle ergometry tests, biomicroscopy of bulbar conjunctiva allows early detection of subclinical and initial manifestations of cerebral circulatory failure (CCF) in CCHD patients. Quantitation of cerebral circulation at graded exercise test according to specially devised criteria is intended for differentiation of subclinical CCF in CCHD patients from age-specific changes in cerebral vessels and residual brain pathology of nonvascular genesis. Using a discriminant analysis of risk factors, ECG and echo-CG findings, the authors have designed a method of predicting dyscirculatory encephalopathy in CCHD patients free of cerebrovascular symptoms. The method can contribute to advanced efficacy of preventive and therapeutic measures in coronary patients. PMID- 8009927 TI - [Hormonal heterochronia in the stress-regulating system in cerebral ischemia]. PMID- 8009928 TI - [A comparison of the results of topographic EEG mapping with the data from a neurological examination and computed tomography of the brain]. AB - The data of topographic EEG brain mapping were compared to neurological evidence and CT data in 6 patients with organic lesions (sequelae of vertebrobasilar ischemic stroke, brain atrophy, brain tumor). Cortical activity typical for these nosological entities appeared on the EEG maps. In 5 out of 6 patients foci of alpha- and delta-activity indicated the location of the lesion. The authors suggest that EEG brain mapping of the large number of patients with neural and mental diseases will provide insight into pathogenetic mechanisms of these diseases. The authors also think it necessary for patients undergoing EEG brain mapping to be examined neurologically. PMID- 8009929 TI - [The clinico-hemodynamic characteristics of atherosclerotic circulatory encephalopathy]. AB - The authors studied intracranial hemodynamics in atherosclerotic dyscirculatory encephalopathy (DCE) using extra- and intracranial ultrasound examinations, discuss stage-specific clinical features of DCE, evaluated extracranial arteries, measured collateral blood flow and linear blood flow rate along the intracranial arteries depending on DCE stage. PMID- 8009930 TI - [The hypothalamic syndrome in childhood (its epidemiological and clinico electrophysiological aspects)]. AB - The epidemiological survey covered 2000 city schoolchildren. They ranged in age from 7 to 15 years. Hypothalamic deficiency (HD) was detected in 5% of the examinees. Clinical and physiological findings on HD children are provided. They were found to have the history of hereditary or natal damage evidencing the acquired nature of the disease. Special emphasis is placed on HD manifestations in prepubertal and pubertal age. The authors show defective regulation of nonspecific brain systems in the form of predominant activation of the septohippocampal system and relative insufficiency of the brain stem mesencephalic reticular formation. Activation of cerebral ergotropic vegetative mechanisms combines with peripheral vegetative failure (sympathetic and parasympathetic), probably, of congenital origin. PMID- 8009931 TI - [Clinical differences in senile dementia of the Alzheimer's type and in multi infarct dementia]. AB - Impoverished grasp of the abstract and the essential notions (IG) and delusion of stealing (DS) were investigated in Alzheimer's senile dementia (ASD) and multi infarction dementia (MID). IG severity was evaluated in impairment of memory and disorientation in 67 ASD and 70 MID patients. DS was studied in 24 ASD and 56 MID patients. It was found that in similar impairment of memory and disorientation, IG was more distinct in ASD, especially at early stages of the disease. DS occurred more frequently in ASD than in MID. In MID the IG and DS symptoms were more common and severe in patients over 80. No age-specific relations were recorded in ASD. The findings suggest involvement of cerebral senile-atrophic processes in IG and DS genesis in MID patients. PMID- 8009932 TI - [The social and occupational adaptation of schizophrenia patients with different clinical structures of the negative disorders in remission]. AB - The authors examined 171 patients suffering from shift-like schizophrenia taking its course with remissions free of psychotic disorders. Negative symptoms were studied by means of an original three-dimensional scale taking into account the severity, sphere and characteristics of the mental disturbance. New data were obtained on development and time course of negative disorders at different stages of the illness. The most frequent patterns of the defects observed in remission were characterized in accordance with combination of quantitative and qualitative disorders. The basic types of compensatory-adaptation defenses were described and the structural and clinico-dynamic effects of the negative disorders on their forming was shown. The data obtained may help improve the effectiveness of rehabilitation of patients suffering from schizophrenia. PMID- 8009933 TI - [The clinico-psychological diagnosis of the personality changes in the initial period of epilepsy]. AB - The authors present the approach to clinicopsychological diagnosis of personality disorders in initial epilepsy based on clinical evidence on 200 epileptics versus 40 healthy controls. 10 experimental techniques have been used. The comparative analysis of the findings obtained at initial stage of the disease and at late stages (within 3 vs. 10 and more postdiagnosis years, respectively) against relevant characteristics of the controls demonstrated that personality disorders within the initial 3 years of the disease are either minimal or absent and can be identified only by the methods of psychological diagnosis. The latter is important for design of adequate therapy. PMID- 8009934 TI - [The wives of alcoholics: experience in the study of psychopathology]. AB - The authors examined clinically 215 wives of alcoholics or divorced women who had been previously married to alcoholics. None of the women abused alcohol. Only 12 of them were officially registered as psychiatrist's patients. Borderline psychopathological conditions were diagnosed in 174 women who had long been married to alcoholic husbands or lived with them in one apartment. Of them, psychopathy, neurotic personality, neurosis, reactive depressions were identified in 27%, 24.7%, 23%, 15%, respectively. 41 divorced women living apart from former alcoholic husbands had no psychopathology at the moment of the study. Borderline neurotic disorders in alcoholic husbands' wives should be considered in familial analysis made for subjects seeking genetic advice. PMID- 8009936 TI - [The structural-functional properties of the erythrocyte membranes in patients with ischemic stroke and circulatory encephalopathy]. AB - 68 patients with cerebrovascular disorders (37 cases of ischemic stroke and 31 cases of dyscirculatory encephalopathy) were examined for microhemorheology (erythrocytic form and deformability); fractional composition of neutral lipids; blood phospholipids; those in red cells and their membrane environment (ME); erythrocytic sorption capacity in plasma and ME by fibrinogen. Neutral lipids were found to undergo metabolic disorders manifested as lowered amount of phospholipids, elevated levels of free fatty acids, triglycerides and cholesterol ethers. The fractional composition shifted to a growing toxic fraction of lysophosphatides and reducing fraction of phosphatydilcholine. The changes were of the same type in all the tested media and seemed interrelated. Along with alterations in the membrane lipid composition there appeared functional changes in erythrocytes: deformability decreased, echinocytes emerged, membrane sorption capacity enhanced, ME fibrinogen rose. PMID- 8009935 TI - [The use of baclofen for treating affective disorders in alcoholism]. AB - 90 patients with alcoholism stage II suffering from secondary affective disorders (anxiety, depression) were divided into 4 groups: treated with GABA-B-receptor ligand baclofen (group 1), with sibazon (group 2), amitriptylin (group 3), placebo (group 4). As shown by clinical, experimental psychological and electrophysiological examinations, baclofen is not inferior in efficacy to sibazon and amitriptylin, but is free of side effects and complications typical for the above drugs (central deprivation, addiction, etc.). MAO activity was unaffected in all the patients, so were dopamine, serotonin and GABA blood concentrations after the treatment. This does not allow to relate the peripheral metabolism of GABA and monoamines to emergence of secondary affective disorders in alcoholism. The authors think promising to seek for drugs effective against affective disorders among ligands of GABA-B receptors. PMID- 8009937 TI - [The effect of dalargin on the opioid and immune systems in patients with a depressive syndrome]. AB - Depressed patients and healthy donors received dalargin. As shown by the radioreceptor test, the patients recovered normal quantitative and qualitative values of plasma opioid activity due to this drug which is a synthetic agonist of sigma-type opioid receptors. Lymphocyte proliferative activity (spontaneous and induced by polyclonal mitogens) was not significantly different in the test subjects versus the donors, though in vitro studies revealed multidirectional homeostatic effects of dalargin. It is shown that depressions are associated with defective relationships between functions of the immune and opioid system. Dalargin proved uneffective in the treatment of endogenic psychotic depressions, whereas in reactive neurotic depressions and psychosomatic abnormalities the drug is promising and needs further investigations. PMID- 8009938 TI - [The clinico-tomographic correlates in Alzheimer's disease]. AB - Brain computed tomographic scans of 43 patients with Alzheimer's disease (moderate and severe dementia) were compared to those of age-matched normal subjects (30 controls). Computed tomographic analysis included some linear and volume ventricular measurements. These indices correlated with relevant psychopathological and psychometric findings. Linear measurements of the ventricular size and the degree of cortical, central atrophy were significantly greater in patients with Alzheimer's disease than in the control group. In line with the disease progression and its development from moderate to severe dementia the degree of brain structural changes increased with the predominance of cortical atrophy in parietal lobes and central atrophy in mediobasal parts of the temporal lobes. PMID- 8009939 TI - [The dynamics of the clinico-psychological characteristics of neurotic patients during group therapy]. AB - The authors followed up clinical and psychological characteristics obtained for 85 neurotic patients taking group psychotherapy. As a result of the study prognostically favourable clinical features have been established: initial stages of the disease, prevalent phobic and somatic-vegetative disorders, sensitive accentuation of the temperament. Among the unfavourable parameters are the neurotic stage and hypochondria. Patients with high efficacy of the treatment are very sensitive to rejection. They have motivation to appreciate the causes and psychological mechanisms of their disease, orientation on their own efforts in achieving important purposes in life. Insignificant responses were reached in patients with low sensitivity to rejection. Their system of values is contradictory in unclear ideas of life purposes and means of their realization as well as own participation in positive life programs. PMID- 8009940 TI - [A clinico-psychological analysis of the characteristics of patients with an asthenic syndrome of a psychogenic and somatogenic nature]. PMID- 8009941 TI - [The mental reactive characteristics of patients with neurasthenia and hypertension during frustration]. AB - The response to stress was compared for neurotic subjects and initial hypertension patients. The stress was simulated using Rosenzweig frustration method. The neurotic patients responded by profound psychological revision of the stress situation, complicated relationships of the inner reactions and their apparent manifestations. Hypertensive subjects had less profound emotions, their psychological responses were close to those of healthy subjects. PMID- 8009942 TI - [A case of the successful use of regional thrombolytic therapy in acute ischemic stroke]. AB - The paper reports a case of a positive response to fibrinolytic therapy with complete lysis of the thrombus in the left internal carotid artery (ICA) and significant reduction of the baseline neurological deficiency. The vessel later on underwent rethrombosis, but the patient's condition remained stable. Acute ICA occlusion, recovery of the major circulation and subsequent rethrombosis were confirmed angiographically. The intraarterial thrombolytic therapy started 12 hours after the apoplexy. The relief of the major artery occlusion in an acute period of cerebral ischemia prevented the development of infarction and promoted adequate collateral circulation due to which subsequent rethrombosis appeared asymptomatic. It is suggested that intraarterial fibrinolytic agents may be effective as well at later postapoplectic periods (after 6 hours and later). PMID- 8009943 TI - [A case of temporal arteritis]. PMID- 8009944 TI - [The clinico-neurophysiological study of the effect of cerebrolysin on brain function in the acute and early recovery periods of hemispheric ischemic stroke]. AB - Thirty patients with acute ischemic stroke and at early terms of postapoplectic recovery received cerebrolysin in daily doses 10, 20 and 30 ml for 5 days or 10 ml, i. v. for 10 days, respectively. The patients were examined for neurological status and cerebral function. In acute stroke the highest effect occurred in the affection of moderate severity. In severe stroke the drug stimulated recovery of impaired functions which tended to restore more quickly than in control subjects. In early convalescents cerebrolysin improved motor functions. Details of the results of the combined neurophysiological examination in the course of the treatment are discussed. PMID- 8009946 TI - Development of a least restraint program--one hospital's experience. PMID- 8009945 TI - [Torticollis spastica (a review)]. PMID- 8009947 TI - Pressure ulcers: current approaches to prevention and management. PMID- 8009948 TI - A lifetime of memories: a community development pilot project. PMID- 8009949 TI - Functional outcomes of rehabilitation in the frail elderly: a two-year retrospective review. PMID- 8009950 TI - And speaking of patient safety. PMID- 8009951 TI - Ethics in the workplace: whistleblowing. PMID- 8009952 TI - Breach of trust. PMID- 8009953 TI - Impact of health care cuts: nurses' stories. PMID- 8009954 TI - Analysis of p53 gene mutations in low- and high-grade astrocytomas by polymerase chain reaction-assisted single-strand conformation polymorphism and immunohistochemistry. AB - Using polymerase chain reaction-assisted single-strand conformation polymorphism (PCR-SSCP) and immunohistochemical analyses, mutations in the p53 tumor suppressor gene were examined in 19 low- and high-grade gliomas. By PCR-SSCP and nucleotide analyses, p53 gene mutation was seen in 7 gliomas. Out of the 7 mutations, 3 were located at the CpG site of the previously proposed hot-spot codons 248 and 273, 2 were at codons 171 and 214 and the other 2 were in intron 5, 1 at the splice acceptor site and the other in the vicinity of the splice donor site. The latter 4 mutations have not, or only rarely, been observed in gliomas or in other tumors. However, their effect on the structural and functional alteration of the p53 protein was suggested by positive intranuclear p53 immunostaining in neoplastic cells in 3 mutations including the 1 at the splice acceptor site. In connection with glioma grading, the p53 gene mutation was shown to have occurred in both low- and high-grade gliomas, often in most of the neoplastic cells, as suggested by lack of distinct normal bands and ladders in SSCP and direct sequencing, respectively. The absence of recurrence and malignant transformation over a considerably long postoperative time in our low grade glioma cases suggested that the p53 gene mutation might not be sufficient for the progression from low- to high-grade gliomas. The frequency of detection of mutation was 7/19(37%) by PCR-SSCP, 8/19(42%) by immunohistochemistry and 10/19(53%) by both methods. The results of PCR-SSCP and immunohistochemistry were consistent in 14 cases (73.7%), but not in 5 cases(26.3%).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8009955 TI - Beta-amyloid formation by myocytes of leptomeningeal vessels. AB - Ultrastructural study of the leptomeningeal vessels of three subjects with Alzheimer's disease (AD) shows that beta-amyloid deposits in the media of arteries and arterioles are produced by smooth muscle cells. It appears that the soluble beta-protein secreted by sarcolemmal vesicles of the muscle cell polymerizes into amyloid fibrils in basal lamina. Myocytes trapped in amyloid deposits degenerate and die. The most common and severe degeneration of smooth muscle cells is seen in the external and medial zone of the vascular media. In more advanced stages of amyloidotic changes, the internal zone of media is also involved. The media of vessels with severe changes consists of amyloid deposits and cell debris. Amyloid fibrils around the dead myocytes also undergo degradation. They lose their fibrillar appearance and become floccular, granular, amorphous proteinous material; however, this material is continually positive in immunostaining for beta-amyloid. This study suggests that amyloid formation by smooth muscle cells involves a secretory path. Our data indicate that the smooth muscle cell secretes nonfibrillar beta-protein or beta-protein containing peptides and that conversion of nonfibrillar into fibrillar beta-amyloid takes place in the environment of the basement membrane. PMID- 8009956 TI - Long-term effects of intermittent versus continuous ethanol exposure on hippocampal synapses of the rat. AB - The hippocampus is known to be very sensitive to a large spectrum of different neurotoxins including ethanol. Ethanol administered continuously or intermittently may affect the hippocampus in different ways. Intermittent administration of ethanol has many features in common with the low level electrical stimulation protocols which lead to the functional changes associated with the phenomenon of kindling. In this study, the differential effects of intermittent intraperitoneal ethanol injections (3 g/kg twice daily) and continuously administered ethanol in drinking water (20%) on hippocampal synapses in the rat were studied using ethanolic phosphotungstic acid staining and electron microscopy. After 1 month of intermittent exposure a significant reduction (18%) of synapses was seen in the stratum lucidum of the CA3 region. Continuously treated animals showed no significant change over this time despite a higher total ethanol intake. In the dentate gyrus, a compensatory increase in supragranular synaptic number was seen only in continuously treated animals. These findings demonstrate the sensitivity of synapses of the hippocampus to the presence of ethanol and the larger effects of peaking ethanol concentrations compared to more constant levels. These results emphasize the need to consider the differential effects of various types of ethanol consumption also on the human brain. PMID- 8009957 TI - Post-traumatic brain hypothermia reduces histopathological damage following concussive brain injury in the rat. AB - The purposes of this study were (1) to document the histopathological consequences of moderate traumatic brain injury (TBI) in anesthetized Sprague Dawley rats, and (2) to determine whether post-traumatic brain hypothermia (30 degrees C) would protect histopathologically. Twenty-four hours prior to TBI, the fluid percussion interface was positioned over the right cerebral cortex. On the 2nd day, fasted rats were anesthetized with 70% nitrous oxide, 1% halothane, and 30% oxygen. Under controlled physiological conditions and normothermic brain temperature (37.5 degrees C), rats were injured with a fluid percussion pulse ranging from 1.7 to 2.2 atmospheres. In one group, brain temperature was maintained at normothermic levels for 3 h after injury. In a second group, brain temperature was reduced to 30 degrees C at 5 min post-trauma and maintained for 3 h. Three days after TBI, brains were perfusion-fixed for routine histopathological analysis. In the normothermic group, damage at the site of impact was seen in only one of nine rats. In contrast, all normothermic animals displayed necrotic neurons within ipsilateral cortical regions lateral and remote from the impact site. Intracerebral hemorrhagic contusions were present in all rats at the gray-white interface underlying the injured cortical areas. Selective neuronal necrosis was also present within the CA3 and CA4 hippocampal subsectors and thalamus. Post-traumatic brain hypothermia significantly reduced the overall sum of necrotic cortical neurons (519 +/- 122 vs 952 +/- 130, mean +/- SE, P = 0.03, Kruskal-Wallis test) as well as contusion volume (0.50 +/- 0.14 vs 2.14 +/- 0.71 mm3, P = 0.004).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8009959 TI - Extracellular or ghost Pick bodies and their lack of tau immunoreactivity: a histological, immunohistochemical and electron microscopic study. AB - Histological, immunohistochemical, and electron microscopic evidence of an extracellular, or ghost Pick body has been found in the granular cell layer and, rarely, in the pyramidal cell layer of the hippocampus of an autopsy case of Pick's disease. The ghost Pick body appeared as a blurred, weak argyrophilic mass in the neuropil, and it was composed of accumulated fibrillary structures, 13 nm in diameter, intermingled with glial filament bundles. These ghost Pick bodies did not react with anti-tau and anti-ubiquitin antibodies, but did react weakly with anti-glial fibrillary acidic protein antibody, whereas intracytoplasmic Pick bodies were strongly immunolabeled with anti-tau but only weakly with anti ubiquitin antibodies. These results suggest that the Pick body is discharged into the neuropil after destruction of the mother neuron, loses its immunoreactivity to certain tau and ubiquitin antibodies during this process (thereby inducing a glial reaction) and remains in the neuropil as a ghost Pick body. PMID- 8009958 TI - Nervous system inflammatory lesions and viral nucleic acids in rabbits with herpes simplex virus encephalitis-induced rotational behaviour. AB - Rabbits with herpes simplex virus (HSV) encephalitis induced by corneal virus challenge exhibit rotational behaviour linked with altered brain dopamine functions. The neuropathology and the distribution of the HSV-specific nucleic acids were studied, using probes for the viral trans-inducing factor alpha TIF and for the latency-associated transcript LAT-1 RNA to detect productive and latent infections, respectively. The rotational behaviour began 4 days after inoculation, and at that time the inflammatory process was observed only in the brain stem and the productive infection, revealed by in situ hybridisation, was seen in the trigeminal entry and nuclei. No HSV-specific nucleic acids or neural destruction were observed in the regions of the serotoninergic raphe or dopaminergic substantia nigra. At 8 days after inoculation, when the rotational behaviour was beginning to attenuate, the inflammatory lesions spread into the hemispheres, involving particularly the ventral parts of the limbic system including the olfactory system. In no cases were HSV-specific nucleic acids detected in the olfactory system. The inflammation in the limbic system was also detectable in animals without inflammatory lesions in the olfactory bulbs or tracts, suggesting that the infection had spread from the brain stem. The present study shows that in this model the altered neurotransmitter functions observed previously, appearing as rotational behaviour, occur without productive infection or necrosis, suggesting specific interaction of HSV with monoaminergic neurons. Additionally, the results suggest that HSV could reach the limbic system via ascending serotoninergic projections from the raphe neurons. PMID- 8009960 TI - Cholinesterases colocalize with sites of neurofibrillary degeneration in aged and Alzheimer's brains. AB - Acetylcholinesterase and butyrylcholinesterase have been associated with structures undergoing neurofibrillary degeneration, as well as with all types of senile plaques, in non-demented aged and Alzheimer's brains. At the electron microscope level, the reaction product of both enzymes, appeared to decorate paired helical filaments, straight filaments and beta A4 amyloid fibrils. Recent studies showed that cholinesterases were associated with amyloid at early stages, e.g., in diffuse plaques. In the present study, the interrelationship of cholinesterases to structures undergoing neurofibrillary degeneration was analyzed further. Tau immunoreactivity was compared to the staining pattern observed with the two esterases. Double protocols consecutively performed on the same sections, and counterstaining with thioflavin-S, confirmed the presence of cholinesterases in all structures with neurofibrillary degeneration. The conclusion that cholinesterases consistently colocalize with both neurofibrillary bundles and beta A4 amyloid fibrils at all stages of their accumulation, allows us to speculate on the possible role that these enzymes may play in either the formation or the consolidation of fibrillary aggregates. PMID- 8009962 TI - Uncompacted myelin lamellae in polyneuropathy, organomegaly, endocrinopathy, M protein and skin changes syndrome. Ultrastructural study of peripheral nerve biopsy from 22 patients. AB - Mechanisms of peripheral neuropathies in polyneuropathy, organomegaly, endocrinopathy, M-protein and skin changes (POEMS) syndrome are poorly understood. A peripheral nerve biopsy was performed in 22 patients. Of these 9 had histological features of Castleman's disease on lymph node biopsies, and 19 had a monoclonal lambda light chain in their serum. Certain nerve fragments were paraffin embedded, others were frozen and studied by direct immunofluorescence, and others were fixed for ultrastructural examination. Paraffin-embedded fragments did not show any amyloid deposits, and at direct immunofluorescence there was no immunoglobulin fixation. At ultrastructural examination, features of uncompacted myelin lamellae (UML) were present in 19 patients, and their frequency varied from 1% to 16% of myelinated fibres. Up to now UML have been reported only in 7 patients with POEMS syndrome in the literature. UML have also been noticed in a few cases of inflammatory demyelinating polyradiculoneuritis and inherited tendency to pressure palsy. PMID- 8009961 TI - Evidence for an origin of ethyl-nitrosourea-induced rat central nervous system tumors from pluripotent germinal neuroepithelium. AB - Brain tumors induced by transplacental application of ethyl-nitrosourea (ENU) in F344 rats were immunohistochemically demonstrated to consist of undifferentiated cells, astriocyte-like cells, oligodendroglia-like cells, and two distinct types of vimentin-expressing cell groupings termed as perivascular small cell nests (PSCNs) and large cell nests (LCNs). Co-distribution of vimentin and glial fibrillary acidic protein (GFAP) was sparsely observed in the astrocyte-like cells, which suggested an immature glial phenotype. PCSNs contained cells expressing GFAP, neuron-specific enolase (NSE), beta-tubulin isotype III, and low affinity nerve growth factor receptors (LNGFRs). LCNs contained cells showing a neuronal phenotype with expression of low- and middle-molecular mass neurofilament proteins (NF-L and -M) as well as NSE, beta-tubulin isotype III and LNGFR. Double-labelling immunohistochemistry revealed the NF-L-expression in LNGFR-positive LCN-forming cells. Oligodendroglia-like cells and their intercellular neuropil-like structures expressed beta-tubulin isotype III, synaptophysin and NSE, in addition to the expressions of vimentin and GFAP. Electron microscopically, synapse-like structures were formed between these oligodendroglia-like cells and their dendritic processes. Topographically, bidirectional cell transitions from PSCNs to astrocytes and LCNs were indicated. The present study strongly suggests that so-called ENU-induced "gliomas" originate from pluripotent germinal neuroepithelium. Furthermore, LNGFR expression may be responsible for acquisition of neuronal phenotype in these tumors. PMID- 8009963 TI - A role for extracellular matrix degradation and matrix metalloproteinases in senile dementia? AB - In brain as in cartilage, the extracellular matrix contains aggregates formed by hyaluronic acid (HA) and proteoglycans. In osteoarthritic cartilage, release of the proteoglycans from the aggregates by cleavage of the HA-binding region results in the accumulation of the HA-binding region and in the fragmentation of the released proteoglycans. Stromelysin, a matrix neutral metalloproteinase, is one of the enzymes responsible for the cleavage of the HA-binding region. We suggest that a similar process also occurs in senile dementia. The brain proteoglycan contains sequences identical to those of aggrecan, which are recognized and cleaved by stromelysin, and is, in fact, susceptible to stromelysin digestion. Monoclonal antibodies reacting with glial HA-binding protein, but not with the parent protein, stained several senile plaques as defined by their reactivity with antibodies to the amyloid-beta protein in double labeling experiments. PMID- 8009964 TI - Histochemical study of mitochondrial enzymes in cerebellar cortex of macular mutant mouse, a model of Menkes kinky hair disease. AB - The cerebellar Purkinje cells in the hemizygote of the macular mutant mouse contain numerous abnormal mitochondria which show a marked decrease in cytochrome c oxidase activity. Using histochemical methods we studied the activity of other mitochondrial enzymes, such as NADH diaphorase and succinic dehydrogenase, in the cerebellar cortex of this mutant mouse. Such activities were markedly increased in the Purkinje cells, especially in the soma and stem dendrite, from 10 days after birth in the hemizygote as compared with findings in normal littermates. These results were considered to be due to an increased number of abnormal mitochondria. PMID- 8009966 TI - African crescendo. Statistical aspects of a lethal epidemic. PMID- 8009965 TI - The microvascular changes in cases of hereditary multi-infarct disease of the brain. AB - A report on a cerebro-vascular disease with autosomal dominant inheritance, characterised by stroke-like episodes beginning in early adulthood and progressive dementia, afflicting one family living in Sweden was presented in 1977. Another afflicted member showing gait and coordination disturbances and impaired cognitive functions is now introduced. Magnetic resonance imaging revealed multiple brain lesions indicating ischaemic injuries. Previous autopsy studies of other cases revealed white matter atrophy, multiple infarcts and lacunes. In one patient who had died from a cerebral haemorrhage, obliteration of intracerebral arteries, occasionally with organised thrombi was present. Autopsy material has now been reinvestigated with special attention to changes of intracerebral arterioles. Cases with long duration of the disease presented pronounced fibrous thickening of the wall of numerous intracerebral arterioles, degeneration of smooth muscle cells of the media and obliteration of the lumen. Immunohistochemistry showed marked expression of fibrillary collagen types I, III and V and of the basal lamina components collagen type IV and laminin. These depositions are probably induced by some primary dysfunction of smooth muscle cells or endothelial cells. Perivascular reactive astrocytes with endothelin-1 like immunoreactivity were present in some brain regions. Endothelin-1 is the most powerful vasoconstrictor peptide known to date. Structural remodelling of intracerebral arterial vessels, actions of different vasoactive factors and rheological disturbances may all interfere with local blood flow in this disease and cause the parenchymal changes of the brain. PMID- 8009967 TI - Recurrent abortions and lymphocyte transfusions. AB - Normal pregnancies depend on successful implantation of the placenta in the uterus. The trophoblast which forms the ultimate interface between the fetal and maternal tissue seems to lack the foreign (allo) antigens (namely HLA/TLX) required to induce immunological rejection reactions in the mother. It was previously believed that the trophoblast expressed paternal allo antigens and that successful pregnancies were dependent on so called 'kind' (non-cytotoxic or non-complement binding) blocking antibodies in order to protect the fetal unit from maternal cytotoxic T-cells and -antibodies. Blocking antibodies attached to paternal antigens on the trophoblast were assumed to prevent maternal cytotoxic T cell and cytotoxic antibodies from recognising the trophoblast as foreign tissue. On this assumption it was reasoned that transfusions of paternal HLA-expressing lymphocytes would increase maternal antipaternal HLA (TLX) blocking antibodies and thus be beneficial to women who experienced multiple miscarriages. There is, however, no scientific evidence for a specific immune response after lymphocyte transfusions that fulfil this function. Immunological tests, as for example mixed lymphocyte culture (MLC), on peripheral blood lymphocytes do not seem to reflect the local immune state in the uterus, either in the pregnant or the non-pregnant state. Since the trophoblast forms the ultimate interface between fetal and maternal tissue, its structure, secretions, and interaction with the decidua must be of definite importance for implantation of the blastocyst and growth of the embryo. PMID- 8009968 TI - Morphometric analysis of gap junction density in human myometrium at term. AB - In the human myometrium, the formation of gap junctions in the various stages of labor and, in correlation with the concentration of progesterone in the maternal blood, has not been described adequately. The accepted hypothesis that raised concentrations of progesterone in maternal blood in animals prevent the formation of gap junctions was scrutinized in human myometrium. Myometrial tissue was examined by electron microscopy for the presence of gap junctions and analyzed morphometrically in 17 women who had an elective or emergency cesarean operation at the 38th or 39th week of pregnancy. The concentrations of progesterone and estradiol in the maternal and cord blood was measured by means of radioimmunoassay. The frequency and area of gap junctions varied in relation to the presence or absence of labor. In the myometrium of women in labor, gap junctions were most frequent (5.2/1000 microns of cell membrane), their area largest (0.32 microns 2/1000 microns of cell membrane) and their fractional area greatest (0.20%). When the women were not in genuine labor or when contractions were weak, the percentage fractional areas of gap junctions were low (0.020 0.090) and the gap junctions very small. In the pre- and active phases of labor, the concentration of progesterone in maternal blood was significantly higher (p < 0.025 and 0.03 respectively) than in women who were not in labor. Hence, despite high concentrations of progesterone in the maternal and cord blood at term, the myometrium presented numerous gap junctions of relatively large area. PMID- 8009969 TI - Antiphospholipid antibodies and risk of intrauterine late fetal death. AB - STUDY OBJECTIVE: Goal of the study was to analyze the relationship between anticardiolipin antibodies, lupus anticoagulant and the risk of intrauterine late fetal death. DESIGN: A case-control study was conducted in a network of general and teaching hospitals in northern Italy. Cases studied were 99 women (median age 27 years), without clinical evidence of systemic lupus erythematosus or other immunological disorders who had an 'unexplained' intrauterine fetal death at or after the 20 weeks of gestation. The control subjects were 85 women (median age 28 years) who gave birth at term (> 37 weeks gestation) to healthy infants on randomly selected days at the same hospitals where cases had been identified. RESULTS: The presence of lupus anticoagulant was detected in four of the 99 cases (4%, 95% confidence interval 2%-15%) and none of the 85 controls. A total of 10 out of the 89 cases (11%, 95 confidence interval 6%-23%), but none of the 79 controls for whom anticardiolipin antibodies value was available had elevated anticardiolipin antibodies; this difference was statistically significant (chi 2(1) = 9.38, p < 0.01). PMID- 8009970 TI - Calcium homeostasis in normal pregnancy and puerperium. A longitudinal study. AB - Calcium homeostasis was longitudinally followed in serum and urine throughout normal pregnancy and the puerperium in 23 healthy women. From the 14th week of gestation, samples were obtained every fourth week until the 38th week. Post partum samples were obtained on the fifth day and after eight weeks. In the serum the total calcium decreased continuously during pregnancy. The ionized calcium and phosphate levels remained unchanged and within the reference interval for non pregnant women. The alkaline phosphatase level progressively increased and high levels were found at term. The magnesium and hematocrit values remained below, whereas the calcitonin level remained just above the reference interval throughout pregnancy. The parathyroid hormone was low initially and increased towards term but within the reference interval. The urine excretion of calcium was constantly high, close to the upper reference limit, and renal function was slightly improved. At the last sampling eight weeks after delivery, all values were within normal limits for non-pregnant women. Calcium homeostasis is considerably changed during pregnancy and non-pregnant reference limits are not often valid. PMID- 8009971 TI - Disposition of 5-aminosalicylic acid and N-acetyl-5-aminosalicylic acid in fetal and maternal body fluids during treatment with different 5-aminosalicylic acid preparations. AB - STUDY OBJECTIVE: To determine the concentration of 5-aminosalicylic acid (5-ASA) and the metabolite N-acetyl-5-aminosalicylic acid (Ac-5-ASA) in the maternal and fetal plasma at delivery and in the maternal milk post partum. DESIGN AND STUDY SUBJECTS: Pregnant and lactating women with chronic inflammatory bowel disease, treated with different pure 5-ASA preparations participated in the study. At delivery, samples of fetal and maternal plasma were obtained from nine women. The excretion in milk was measured and the time of medicine intake was registered during a 24 h period 2-4 weeks after delivery in 13 women. RESULTS: Concentrations of 5-ASA in the fetal plasma were lower than in maternal plasma. Plasma concentrations of Ac-5-ASA were detectable in all the nine samples and similar levels in the mother and the fetus were found at the time of delivery. In three women 5-ASA was detected in the milk in low concentrations. The concentration of Ac-5-ASA in the milk varied considerably during the 24 h collection period, and also between individuals; its concentration tended to be higher than in the plasma. No time relation between medicine intake and maximal concentration in the milk was found. Based on the maximal Ac-5-ASA concentration and a milk intake of one liter/daily, the newborn receives less than 15 mg Ac-5 ASA daily. CONCLUSION: The study indicates that treatment with pure 5-ASA preparations in conventional doses is without risk to the fetus and the newborn. PMID- 8009972 TI - Multifetal pregnancy reduction in Sweden. Utilization rate and pregnancy outcome (1986-1992) AB - All departments of Obstetrics and Gynecology, as well as all private clinics in Sweden offering assisted conception, were surveyed by means of a questionnaire to determine the utilization rate and outcome of multifetal pregnancy reduction (MFR) for the period 1 January 1986 to 30 June 1992. The response rae was 100%. Multifetal reduction was performed in 26 women, giving an average utilization rate of 1/7 multiple births of three or more for the entire period. Of the various techniques used, intracardiac or intrathoracic injection of a potassium chloride solution was predominant. The experience of each center with multifetal reductions varied between one and six procedures. In this series, the overall complete pregnancy loss was 27% (n = 7). In 73% (n = 19) of women the pregnancy continued to delivery. One fetus died in utero in the second trimester, one child died from a subtentorial hemorrhage perinatally, and one child had a malformation of the right foot and hand. It seems necessary to limit MFR to a few centers in Sweden in order to maintain and increase the experience of the operators involved, and to decrease the fetal loss rate associated with the procedure. However, the ultimate goal is to make these procedures unnecessary when methods of avoiding excessive ovulation are refined and by limiting the number of replaced embryos in IVF-treatment. PMID- 8009973 TI - Ovarian electrocautery in the treatment of women with polycystic ovary syndrome (PCOS). Factors affecting the results. AB - During the years 1979-91 252 women with polycystic ovarian syndrome (PCOS) have been treated with ovarian electrocautery through the laparoscope in Aker University Hospital. Ovulation was obtained in 92% of the total series, and pregnancy in 84% of the women with PCOS as the sole cause of their infertility. Additional treatment with clomiphene citrate to the non-responders increased the pregnancy rate to 89%. The response to ovarian electrocautery was influenced by body weight, with an ovulation rae of 96-97% in the slim and moderately obese women decreasing to 70% in the really obese ones. When ovulation was established, the pregnancy rate per se was independent of body weight-when ovulation was established, the pregnancy rates of slim and overweight women with PCOS being 92% and 95%, respectively. In the responders (who ovulated following ovarian electrocautery), the annual rate of cessation of ovulation was 3-4% only. Even after a period of contraceptive use following the ovarian electrocautery, ovulation was resumed and pregnancy obtained within a few months. Therefore, ovarian electrocautery is proposed as the primary treatment in women with PCOS undergoing laparoscopy for any reason, infertility being a present, future or hypothetical problem only. When, on the other hand, infertility is not an issue, PCOS per se constitutes no reason to perform laparoscopy. PMID- 8009974 TI - Transvaginal sonography and hysteroscopy in postmenopausal bleeding. AB - We compared transvaginal sonography and hysteroscopy with dilatation and curettage findings in 45 women with atypical postmenopausal bleedings. The histological diagnosis was atrophy in eight (17.8%) women, hormonal effects in 14 (31.1%), endometrial polyp in 19 (42.2%) and adenocarcinoma in four (8.8%). Hysteroscopy detected 16 (78.9%) of the 19 cases with polyps and two of the four with carcinoma. Sensitivity and specificity for endometrial pathology were 86.9% and 91.7% respectively. A polyp was directly diagnosed by transvaginal sonography in 13 (57.9%) women and an infiltrative endometrial cancer in two. Sensitivity and specificity for endometrial pathology were 73.9% and 95.7% respectively. All but one case of endometrial pathology were found when the endometrium (both layers) was thicker than 5 mm. Thus, an endometrial thickness of > or = 5 mm had a sensitivity of 95.7%, a specificity of 45.5% and a positive predictive value of 64.7% for endometrial pathology. This study shows that transvaginal scanning allows detection of an endometrial pathology in the vast majority of cases and it may be used as the first diagnostic step in the investigation of women with atypical postmenopausal bleeding. PMID- 8009975 TI - Osteoporotic fractures in young amenorrheic women. PMID- 8009976 TI - Intramuscular interferon-beta treatment of cervical intraepithelial neoplasia II associated with human papillomavirus infection. AB - A placebo-controlled trial to evaluate the efficacy and the safety of intramuscular injection of interferon-beta has been performed on 37 patients suffering from cervical intraepithelial neoplasia II (CIN II) associated with human papillomavirus (HPV) infection of the cervix: twenty-two patients were treated with interferon-beta (2 x 10(6) I.U. daily) for ten days; fifteen received placebo (2 ml of saline solution daily) for ten days. Prior to therapy, and at day 70, 190, 370, 550, 730 after the beginning of treatment, patients were examined by colposcopy and punch biopsies of the cervix. Results showed a progressive amelioration in the interferon-beta treated patients, which was statistically significant at any control station (70, 190, 370, 550, 730 days) as compared to placebo treatment. Percentages of lesions that regressed, persisted or progressed were 36.4%, 54.5%, 9.1% respectively in the Interferon-beta group, and 0%, 67.7% and 33.3% respectively in the placebo group. Interferon-beta administered intramuscularly has shown to be an efficacious treatment of CIN II (cervical intraepithelial neoplasia II) associated with HPV infection, without evident side effects; it can be used in patients requiring medical treatment with at least one-year monitoring by cervical biopsies or as an adjuvant surgical treatment (which remains the principal treatment) in the management of patients suffering from CIN II associated with HPV infection. PMID- 8009977 TI - A modified technique for correction of the complete septate uterus. AB - When correcting a complete uterine septum, it is recommended that one should spare the cervical portion to avoid the possible risk of cervical incompetence. However, it may be difficult to create a communication between the uterine cavities above the internal os. In seven patients with complete septate uterus we incised the cervical portion with Metzenbaum scissors and the corporal portion with microscissors under hysteroscopic guidance. The operating times were shorter and the distension fluid deficit smaller compared with nine historical controls in whom the cervical septum was spared. No intraoperative or obstetric complications were associated with cervical septal section. This modified technique is simple, rapid, safe, inexpensive, and may be considered among the alternative treatments to correct a complete septate uterus. PMID- 8009979 TI - Uterine rupture. A seat belt hazard. AB - A case is described of a uterine rupture resulting from a car accident occurring in a woman who was wearing a seat belt as generally recommended. The rupture was initially not recognised and only became apparent after attempts to induce labor which led to expulsion of the fetus into the abdominal cavity. PMID- 8009978 TI - In situ DNA hybridization study of 'primary' cytomegalovirus (CMV) oophoritis. AB - We report the case of a 50 year old woman with metastatic breast carcinoma refractory to chemotherapy who died of candidal septicemia after autologous bone marrow transplantation. Although there was no apparent active cytomegalovirus (CMV) infection (negative cultures and serology for active infection), autopsy revealed histologic evidence of CMV inclusions limited to both ovaries. DNA in situ hybridization was performed on multiple organs, and additional foci of infection in one fallopian tube and the adrenal glands were detected. Previous reports of isolated CMV oophoritis may represent sampling error. An ascending route of infection is suggested. Tubo-ovarian changes due to CMV infection may occur more frequently than suspected; they are difficult to diagnose because even actively CMV infected cells may not be detected by routine histology alone, and because, after the active infection 'heals', no evidence of the virus can be found on histologic examination. PMID- 8009980 TI - Hemangioma of the umbilical cord. AB - A case of intrauterine fetal death with a hemangioma and pseudocysts in the umbilical cord is presented. The clinical significance of these rare lesions is not entirely clarified, but of the 20 fully documented cases of umbilical cord hemangiomas, including the present case, only nine were found with live and completely normal infants. PMID- 8009981 TI - Uterine rupture with the use of a low-dose vaginal PGE2 tablet--is it safe? PMID- 8009982 TI - Fertility outcome following surgery for tubal pregnancy. PMID- 8009983 TI - Effect of platelet activating factor antagonist WEB 2086 on the production of TNF from murine peritoneal macrophages. AB - In the present study the effect of platelet activating factor (PAF) antagonist WEB 2086 on the production of tumor necrosis factor (TNF) from primed murine peritoneal macrophages was investigated. At 10(-6) and 10(-5) mol/L, WEB 2086 was found to significantly inhibit LPS induced TNF production from macrophages by activated thioglycollate solution. WEB 2086 inhibition of TNF release began 4 h after LPS stimulation and lasted 22 h with a peek at 16 h. The results showed that PAF might play an important role in the production of TNF. Four methods were compared in the bioassay of TNF. The data demonstrated that L-929 cells treated with actinomycin D and sodium fluoride were the most sensitive for the assay of TNF. This method was employed in this study. PMID- 8009984 TI - [Effects of Phytolacca acinosa polysaccharide on splenic lymphocyte proliferation and cytokine secretion from splenic lymphocyte and macrophage]. AB - The effects of Phytolacca acinosa polysaccharides I (PAP-I), a polysaccharide extracted from Phytolacca acinosa Roxb: on splenic lymphocyte proliferation and cytokines production from splenic lymphocyte and macrophage were studied. Lipopolysaccharides (LPS) and PAP-I were found to significantly augment splenic lymphocyte proliferation of normal BALB/c, nude BALB/c and NC mice in vitro, but concanavalin A (Con A) was shown to stimulate only normal BALB/c and nude BALB/c splenic lymphocyte proliferation. Also, PAP-I significantly enhanced Con A or LPS induced lymphocyte proliferation and mixed lymphocyte reaction. Significant enhancement of colony stimulating factor (CSF) production was observed from splenic lymphocyte of normal BALB/c and nude BALB/c mice but not from NC mice when treated with PAP-I for 5 d. PAP-I was shown to significantly enhance interleukin-2 (IL-2) production from normal mice splenocyte and Con A stimulated normal mice splenocyte in a concentration-dependent fashion. Supernatant of PAP treated macrophage (M phi) were collected and CSF activity was tested. The results confirmed that PAP-I can significantly stimulate M phi to secret CSF activity on d 1. The supernatant also contained a cytokine which exhibited a synergistic action with recombinant murine granular-macrophage CSF (RMGM-CSF) to stimulate mice bone marrow cell proliferation. PAP-I, 5-50 mg.kg-1, ip can enhanced splenic lymphocyte proliferation and IL-2 production. These findings indicate that PAP-I can augment immunologic function in vitro and in vivo. PMID- 8009985 TI - [Determination of glyciphosphoramide and its metabolite in plasma and the pharmacokinetics in rats after oral administration]. AB - Glyciphosphoramide (GPA) is one of the anticancer agents belonging to the group of phosphoramide mustard. It has apparent antitumor effects in some animal models and in clinical trials against breast cancer, lymphosarcoma, uterocervical cancer and cancerous ulcer with good results. In this paper, the determination procedure of GPA and its metabolite using nitrobenzylpyridine (NBP) method is reported. The absorbance of the coloured products from the reaction of hydrolyzed or metabolized GPA with NBP was measured at 570 nm and 564 nm, respectively. The linearity of the reaction for GPA and its metabolite was established over the range of 6.25-100 micrograms/ml water or plasma. The plasma of rats and mice was found to be able to metabolize GPA to form alkylating agent (s) which react with NBP, but that of rabbits cannot. The plasma concentration-time curve of metabolite obtained after oral administration of GPA (100 mg/kg) in rats was shown to fit a two compartment open model with the following parameters: T1/2 beta = 44.5 min, T1/2 alpha = 3.16 min, T1/2 Ka = 2.14 min, T1/2Km = 0.0644 min, Tmax = 7.57 min, Cmax = 55.8 micrograms/ml, AUC = 2827. 39 micrograms/ml.min, K21 = 0.09663/min, K10 = 0.03535/min, K12 = 0.1030/min, Vc = 1.00 L/kg, Vd = 2.07 L/kg, CLt = 2.12 L/h. Kidney was found to be the main organ for GPA metabolite elimination. About one fourth of the given dose was excreted in urine within 24 h with the main portion excreted in the first 2 h. PMID- 8009986 TI - [Synthesis of formyl (acetyl) amino acid and dipeptide derivatives of amino ketones]. AB - Since alpha-acetylaminoacetophenones are known to have antihepatitis activity, a series of aminoacyl and dipeptidyl derivatives were synthesized by replacement of the acetyl group with amino acid and dipeptide acyl groups or by changing the substituents on the benzene ring. Thirty-four compounds were submitted to pharmacological screen for antihepatitis and/or antipeptic ulcer activity. The results showed that the presence of methylene-dioxy group on the benzene ring showed favorable influence on the SGPT-lowering activity of the compounds. PMID- 8009987 TI - [Synthesis and antitumor activity of 4-O-(halogenated) acyl-4' demethylepipodophyllotoxin analogues]. AB - A series of 4-(halogenated)acyl-4'-demethylepipodophyllotoxin analogues were conveniently synthesized by selective esterification in the presence of BF3.Et2O, and screened in vitro against L1210 leukemia and KB cells. Most of these compounds showed marked antitumor activity and exhibited more potent activity than that of etoposide. PMID- 8009988 TI - [Synthesis and antitumor activity of 4-S-(5-amido-1,3,4-thiodiazol-2-yl)4-deoxy 4'-demethylepipodophyllotoxi n analogues]. AB - By the condensation of 4'-demethylepipodophyllotoxin with 2-amino-5-mercapto 1,3,4-thiodiazole in CF3COOH and acylation in the presence of DEPC, 10 title compounds were conveniently synthesized. These compounds were screened in vitro against L1210 leukemia and KB cells, in which compounds SIPI-92-1772, 1774, 1775, 1776, 1777 and 1779 exhibited more potent anti-tumor activity. PMID- 8009990 TI - [The isolation and identification of qianhucoumarin B and qianhucoumarin C from Peucedanum praeruptorum]. AB - Five compounds were isolated from the traditional Chinese medicine Qianhu, roots of Peucedanum praeruptorum. Their structures were identified as 3' angeloyloxykhellactone (IX), qianhucoumarin B (X), qianhucoumarin C (XI), Pd-III (XIII) and peucedanocoumarin III (XV). Among them, X and XI are new compounds, their absolute configurations were elucidated by chemical correlation with khellactones, as 3'(S)-acetoxy-4'(S)-hydroxy-3',4'-dihydroseselin(X) and 3'(S) hydroxy-4'(S)-acetoxy-3',4'-dihydroseselin (XI). Compound IX was isolated from plants for the first time. PMID- 8009989 TI - [Studies on the phenolic derivatives from Galeola faberi Rolfe]. AB - Eight phenolic derivatives, p-hydroxybenzaldehyde (I), 4,4'-dihydroxy-diphenyl methane(II), 2,4-bis(4-hydroxybenzyl) phenol (III), 5-methoxy-3-(2-phenyl-E ethenyl)-2,4-bis (4-hydroxybenzyl) phenol (IV), p-hydroxybenzyl alcohol (V), 4 (beta-D-glucopyranosyloxy) benzyl alcohol (gastrodin) (VI), bis[4-(beta-D glucopyranosyloxy) benzyl] (S)-2-isopropylmalate (VII), bis [4-(beta-D glucopyranosyloxy) benzyl] (S)-2-sec-butylmalate (VIII) were isolated from the rhizome of Galeola faberi Rolfe for the first time. IV and VIII are new compounds. III is a new natural compound. PMID- 8009991 TI - [Chemical constituents of traditional Chinese drug "sheng-ma" (Cimicifuga dahurica)]. PMID- 8009992 TI - [Simultaneous determination of vitamin B1 and vitamin C in aqueous solution with piezoelectric crystal quartz sensors]. AB - According to the response properties of piezoelectric crystal quartz sensors to the solution conductivity the frequency shift response was derived to show a linear dependence on the concentrations of vitamin B1 (VB1) and vitamin C (VC). This was experimentally verified and a calibration model for simultaneous determinations of the two vitamins was established. The usefulness of the technique was evaluated by quantitation of mixtures of unknown composition using common multiple linear regression (MLR) and partial least squares (PLS). The average relative standard deviations for six samples were 4.46% for VB1 and 6.63% for VC with MLR; and 1.97% for VB1 and 2.74% for VC with PLS, respectively. PMID- 8009993 TI - [Determination of gibberellin A3 by reversed phase high performance liquid chromatography]. AB - The analysis of gibberellin GA3 by high performance liquid chromatography (HPLC) was carried out with mu Bondapak C18 column. The developed reversed phase HPLC procedure enables the separation of different GAs with high resolution by means of ionic suppression, including the separation of double bond isomers GA1 and GA3. This method is convenient (without the necessity of derivatization), rapid (15 min for one overall run), sensitive (0.5 microgram is sufficient for precise assay), and has fine linearity (r = 0.999, n = 5) and reproducibility (relative standard deviation < 2%, n = 4). PMID- 8009995 TI - [Isolation and structure of sibirate from Sibiraea angustata]. AB - A new ferulic acid ester, C16H22O9, mp 141-143 degrees C (EtOAc), named sibirate (I), was isolated from the aerial part of Sibiraea angustata (Rchd.) Hand.-Mazz. in addition to a known compound ferulic acid. By means of IR, EI-MS, FAB-MS, 1H NMR, 13C NMR and chemical evidences the structure of sibirate was established as glucityl ferulate. PMID- 8009994 TI - [Characteristics of CDDP-PLA microspheres in vitro and in vivo]. AB - Studies on the drug release in vitro and hepatic arterial chemoembolization in vivo were carried out with the newly developed CDDP-PLA microspheres. The mechanism of the in vitro release was shown to conform to Higuchi equation. After chemoembolization the CDDP-PLA microspheres showed remarkably lower CDDP concentrations in the general circulation and much higher concentrations in the hepatic tissue e. g. up to 21.55 +/- 12.18 micrograms/g at 8 h, which is much higher than that (3.16 +/- 0.09 micrograms/g) of the CDDP in hepatic arterial infusions. Thus, the CDDP-PLA microspheres may improve the curative effects and lower the side effects, especially the kidney toxicity, of the anticancer drug cisplatin. PMID- 8009996 TI - [Intracerebral-ventricular injection of 4-aminopyridine induced convulsion in rabbits]. AB - Intracerebral-ventricular (icv) injection of 4-aminopyridine (4-AP) 8 micrograms to rabbits generated convulsions and epileptic discharges in electrocorticogram (ECoG). With 40 rabbits, the occurrence of convulsion at this dose level was 100%. The results from five rabbits showed that seizures may break out repeatedly at intervals of 1-5 min and such state may last about 1.5 h. Antiepileptic drugs, such as phenytoin sodium, phenobarbital sodium and diazepam, were found to effectively control the seizures provoked by icv 4-AP. Sodium valproate was less effective than the foregoing drugs. The icv 4-AP-induced convulsion appeared to have some merits as compared with the old epilepsy models, such as those induced by electric stimulation, cardiazol, or icv ferrous sulfate. We feel that it may be recommended as a model for the preliminary screening of antiepileptic drugs. The seizures provoked by icv 4-AP were shown to be antagonized by scopolamine, haloperidol, phentolamine, or propranolol, but potentiated by l-dopa. It is now recognized that 4-AP can enhance the release of ACh, DA, and NE in the central nervous system. The present results suggest that the convulsion elicited by 4-AP seems to be related to the disturbance of synaptic transmission in the brain. PMID- 8009997 TI - [Studies on effective reversal of adriamycin-resistant Chinese hamster ovary cell line by verapamil]. AB - A noncytotoxic dose of verapamil (Ver) 3 micrograms/ml was found to potentiate 10 fold the growth-inhibitory effects of adriamycin (ADM) in ADM-resistant Chinese hamster ovary cell line (RC1). Ver 3 micrograms/ml also reduced the IC50 value of ADM from 1.2 micrograms/ml to 0.08 microgram/ml in RC1 in clonogenic assay. The index of reversing resistance was 15-fold. In an attempt to elucidate the mechanism of the reversion of the multidrug resistance by Ver, Ver in combination with ADM was found to enhance intracellular ADM accumulation in RC1, and brought about more toxicity in RC1 than ADM alone; and Ver in combination with ADM was shown to retard RC1 in G2 + M phase by flow cytometry analysis. PMID- 8009998 TI - [The stereoselectivity of chrono-pharmacokinetic parameters of hydratropic acid in rats]. AB - The stereoselective chrono-pharmacokinetic parameters of hydratropic acid in rats were studied. The results showed that under standard light-dark cycle pharmacokinetic parameters of T1/2 alpha and CL are stereoselective and under reverse light-dark cycle, parameters T1/2 beta, AUC, CL, Vc and MRT were shown to be stereoselective. To compare the corresponding parameters of the two different light-dark cycles using t-test, no differences were found in most of them. PMID- 8009999 TI - [Chemical studies on the constituents of Phyllanthus urinaria L]. AB - Two new phenolic compounds (crystal VI and crystal IX) have been isolated from Phyllanthus urinaria L. (Euphorbiaceae). Their structures were determined by analysis of their UV, IR, 1H-NMR, 1H-1H COSY, 13C-1H COSY, long range 13C-1H COSY, DEPT, EIMS and HREIMS spectral data. Crystal VI was determined as methyl brevifolincarboxylate. Crystal IX was elucidated as trimethyl ester dehydrochebulic acid. All of the signals of the 13C-NMR of these two new compounds have been assigned mainly according to DEPT, 13C-1H COSY and long range 13C-1H COSY. Accompanying these two new compounds, 8 known compounds have been isolated. By using chemical reactions, UV, IR, 1H-NMR, MS, their structures were elucidated as n-octadecane(I), beta-sitosterol(III), ellagic acid(IV), daucosterol(V), kaempferol(VII), quercetin(VIII), gallic acid(X) and rutin(XI). Crystal II is an aldehyde, its structure elucidation is in progress. PMID- 8010000 TI - [Studies on the chemical components from leaves of Luffa cylinderica Roem]. AB - Three compounds were isolated from the leaves of Luffa cylinderica Roem. Their structure have been identified as 21 beta-hydroxy-gypsogenin (L-2), 3-O-beta-D glucopyranosyl-arjunolic acid (L-8) and 3-O-beta-D-glucopyranosyl-21-beta hydroxyhederangenin (L-10), respectively, by spectroscopic (IR, 1HNMR, 13CNMR, EI MS and FAB-MS) and chemical methods. L-2 and L-10 are new compounds. PMID- 8010001 TI - [Studies on the structure of alpha-trans-bergamotenol from Chinese santalwood oil]. AB - A new sesquiterpenol was isolated from santalwood oil (Santalum album L., Santalaceae). Its structure and relative stereochemistry were elucidated on the basis of spectral analysis (IR, MS, 1H-1H COSY, 13C-1H COSY and 1H-1H NOESY) as 9(10)Z, alpha-trans-bergamotenol (Ia). PMID- 8010002 TI - [New oxindole alkaloid glycosides from Uncaria sinensis]. AB - Two 16-carboxy derivatives of pentacyclic oxindole alkaloids and its glucopyranosyl esters have been isolated from the ethanolic extract of the leaves of Uncaria sinensis (Olive.) Havil. These structures were deduced on the basis of spectroscopic evidences and chemical correlations, and named mitraphyllic acid (I), isomitraphyllic acid (II), isomitraphyllic acid (16-1)-beta-D-glucopyranosyl ester (III) and mitraphyllic acid (16-1)-beta-D-glucopyranosyl ester (IV). PMID- 8010003 TI - Determination of thiocyanate metabolite of sodium nitroprusside in serum by spectrophotometry. AB - A sensitive, reproducible and rapid method for the spectrophotometric determination of thiocyanate, the metabolite of sodium nitroprusside, was developed. Acetonitrile was used to remove protein in the serum. Uniform design technique was used in arranging the experiments and choosing the reaction conditions between thiocyanate and ferric nitrate reagent. The wavelength of maximum absorption was 456 nm, the calibration curve of SCN- was linear in the range of 1.68-13.4 micrograms/ml (r = 0.9999), the relative average recovery of thiocyanate was 94.0%. The day-to-day and within-day relative standard deviations were less than 4.0% (n = 8) and 3.2% (n = 10) respectively. The limit of determination was 0.3 microgram/ml. Drugs such as lidocaine, etc. presented no interference on the determination. PMID- 8010004 TI - [Synthesis and antibacterial activities of 1-amino-6-fluoro-1,4-dihydro-4-oxo-7 (substituted) piperazinyl-3-quinolinecarboxylic acids and their derivatives]. AB - The title compounds 6-24 were obtained by the reaction of 5 with corresponding benzaldehydes. 5 was prepared with ethyl 7-chloro-6-fluoro-1,4-dihydro-4-oxo-3- quinolinecarboxylate by hydrolysis, amination and condensation with piperazine. Anti-bacterial activities of 5-24 were tested in vitro. PMID- 8010005 TI - [Studies on anti-tumor agents. I: Synthesis and anti-cancer activity of amino acid derivatives of norcantharidin]. AB - In order to search for new compounds with higher anti-cancer activities and lower toxicities, 19 amino acid derivatives of norcantharidin, of which 16 are unknown compounds, were designed and synthesized. Preliminary screening results revealed that 2-(syn-exo-7-oxabicyclo [2.2.1] heptane-2,3-dicarboxylic imido)-N-phenyl glutaramic acid exhibited a fairly apparent inhibitory activity against human hepatoma cells in vitro (inhibitory rate 39.4% at 0.025 mumol/ml). PMID- 8010006 TI - [Studies on some derivatives of crotepoxide--an antitumor constituent of Piper futokadzura]. AB - Through reactions of deacetylation and partial deacetylation with selected opening of epoxide ring, seven derivatives of crotepoxide (futoxide), a known antitumor constituent from Piper futokudzura, were prepared. Preliminary pharmacological tests showed that individual derivative possess significant inhibitory activity at 2 x 10(-4) mol/L to the PAF-induced platelet aggregation, while crotepoxide has no effect even at fivefold of this concentration. PMID- 8010007 TI - [Altered calcium homeostasis in brain aging and senile dementia, new approach to treat Alzheimer's disease]. PMID- 8010009 TI - [Pharmacokinetic analysis of enterogastric circulation of diazepam in rabbits]. AB - The concentration-time curves of diazepam exhibited double peaks after i.v. 5 mg.kg-1 to 6 rabbits. A pharmacokinetic model taking account of enterogastric circulation was proposed to explain this double-peak phenomenon and showed good agreement with data. This model provides not only the ordinary pharmacokinetic parameters: T1/2 (alpha) = 0.21 +/- 0.15 h, T1/2 (beta) = 2.2 +/- 0.6 h, Ke = 1.5 +/- 0.6 h-1, K12 = 2.0 +/- 1.0 h-1, K21 = 1.0 +/- 0.4 h-1, V1 = 3.1 +/- 1.6 L.kg 1, AUC = 1.7 +/- 0.5 microgram.h-1.ml-1, but also the parameters of enterogastric circulation of diazepam: lag time of reabsorption T' = 0.25 +/- 0.24 h, reabsorption rate constant Ka = 3.5 +/- 1.4 h-1, reabsorption rate Ra = 24 +/- 7%. PMID- 8010008 TI - [Intratesticular subcapsular assay, a simple method for the preliminary screening of male contraceptives]. AB - The MB-50 protocol worked out for long by the World Health Organization has been widely employed for the screening of male contraceptives. With this method, 40-80 rats will be used for 1 sample and the course of study will be about 3 months. In view of the high expenses and long duration of time needed, it seems to be not suitable for a preliminary screening. We have exploited a much simpler method, the intratesticular subcapsular assay. The method is as follows: Puncture the scrotal skin and the tunica albuginea at the equatorial plane of the testis just opposite to the epididymis with an intradermal needle fixed at a tuberculin syringe. Then push on the needle for 3-4 mm along the equator parallel to the tunica albuginea. Inject 100 microliters of solution containing 0.1-5 mg of the sample to each testis. To the controls, only the vehicle is injected. One week later the same procedure is repeated and 2 more weeks later, the animals are sacrificed and the data are observed (see Table 1 and 2). In this paper, 7 samples screened with this method were compared with results of the MB-50 method, no positive sample was missed except one false positive sample. These results indicate the coincidence between these two methods. PMID- 8010010 TI - [Effect of DGAVP and Org2766 on intracellular free Ca2+ concentration in dissociated brain cells]. AB - Intracellular free calcium concentration ([Ca2+]i) was measured with Fura-2 in freshly dissociated brain cells isolated from newborn (1-2 day) mouse pups using AR-CM-MIC cation measurement system, and the effects of DGAVP and Org2766 on the changes in [Ca2+]i induced by the protein synthesis inhibitor anisomycin (ANI) were studied. The results indicate that anisomycin caused dose-dependent increases in [Ca2+]i; and DGAVP itself showed no significant effect on [Ca2+]i, but an appropriate dose of DGAVP antagonized the increases induced by the selective dose-range of ANI, suggesting that the antagonism of ANI-induced inhibition of protein synthesis by DGAVP was likely achieved by preventing ANI from increasing [Ca2+]i, but this mechanism did not apply to the other neuropeptide Org2766. Therefore, we suppose that the mechanism of the two neuropeptides are different in terms of their effect on intracellular free calcium concentration. PMID- 8010012 TI - [Synthesis and antitumor activity of 4-(2-amido-2-ethoxycarbonyl) ethylsulfenyl-4 deoxy-4'-demethylepipodophyllotoxin analogues]. AB - Twenty three 4-(2-amido-2-ethoxycarbonyl) ethylsulfenyl-4-deoxy-4' demethylepipodophyllotoxin analogues were synthesized by three steps, in which trifluoroacetic acid was used as a condensation agent of 4' demethylepipodophyllotoxin with L-cysteine ethyl ester hydrochloride without any protection of phenolic hydroxy and amino groups. All compounds were screened in vitro against L1210 leukemia and KB cells, in which, compounds 11, 16 and 18 exhibited more potent antitumor activity than etoposide. PMID- 8010011 TI - [Synthesis and antifungal activity of 1-(2-[(4-substituted-phenyl) methoxy]-2 (substituted-phenyl) ethyl)-1H-azoles]. AB - Twenty nine 1-(2-[(4-substituted-phenyl) methoxy]-2-(substituted-phenyl) ethyl) 1H-azoles were synthesized for searching of more potent and less toxic antimycotic agents. Nine of the title compounds are first reported. Results of preliminary biological tests showed that most of the title compounds exhibited activity against the common pathogenic fungi such as Candida albicans, Microsporum bodin, Trichophyton gypsum, Epidermophyton floccosum, Trichophyton violaceum, Microsporum ferrugincum, Trichophyton rubrum and Microsporum gypsum. The antifungal activity of compound 14 was roughly comparable to clotrimazole and econazole against Candida albicans, but was more active against other test fungi than clotrimazole and econazole. Compounds 4, 5, 6, 12, 23 also have good antifungal activity, but are less active against Candida albicans. PMID- 8010014 TI - [Studies on the diterpenoids on Teucrium quadrifarium Buch-Ham]. AB - Six neo-clerodane diterpenoids were isolated from the acetone extract of Teucrium quadrifarium Buch-Ham (I, II, IV, V, VI and VII). Five of them (I, II, IV, V and VII) were identified as known compounds, teucvidin, 12-epi-teucvidin, teuflin, 19 acetyl-teuspinin and teucvidin, respectively. Compound VI was found to be a new neo-clerodane diterpene, named teuquadrin B. Its structure has been determined from the physical and spectral data. PMID- 8010013 TI - [Studies on the saponin constituents of jiu jielong (Ardisea pusilla)]. AB - Two saponins were isolated from Ardisea pusilla A. DC. which have improved immunological function and antitumor activity. Their structures were determined on the basis of chemical and spectral analysis (IR, MS, 1HNMR, 13CNMR and two new NMR technique). The two compounds were 3-O-[alpha-L-rhamnopyranosyl-(1-->2)-beta D-glucopyranosyl-(1-->3)] [beta-D-glucopyranosyl-(1-->2)]-alpha-L arabinopyranosyl cyclamiretin A (I) and 3-O-[beta-D-xylopyranosyl-(1-->2)-beta-D glucopyranosyl-(1-->4)] [beta-D-glucopyranosyl-(1-->2)-beta-D-glucopyranosyl-(1- >2)]-alpha-L- rhamnopyranosyl cyclamiretin A (II). They were new saponin and named as ardipusilloside I and ardipusilloside II. PMID- 8010015 TI - [Studies on the chemical constituents of Euonymus mupinensis]. AB - Eight compounds have been isolated from Euonymus mupinensis. Their structures were identified by means of physico-chemical and spectral analysis. They are wilforlide A (I), wilforlide B (II), olean-12-en-3,29-diol (III), olean-3-oxo-29 ol (IV), stigmastan-3-one (V), stigmastan-3,6-dione (VI), beta-sistosterol (VII) and beta-sistosterol-3-O-beta-D-glucopyranoside (VIII). Compound IV is a new compound, named as mupinensisone. Compounds I-VIII were isolated for the first time from this plant. 13C-NMR chemical shifts of compounds V and VI were assigned for the first time. PMID- 8010016 TI - [Study on lignans from Diphylleia sinensis]. AB - A new lignan along with eight known lignans and a flavonoid were isolated from the rhizomes of Diphylleia sinensis Li.. Their structures were elucidated on the basis of chemical and spectral analysis. The new lignan, compound IX, was named as picropodophyllin-1-ethyl ether (IX). The eight known lignans were identified as podophyllotoxin (I), isopicropodophyllone (II), dehydropodophyllotoxin (III), diphyllin (IV), picropodophyllin (V), podophyllotoxone (VI), 4' demethylpodophyllotoxin (VII) and picropodophyllin glucoside (VIII). Compounds II, VI, VII and VIII were found for the first time from the rhizome of this plant. The flavonoid was identified as kaempferol. PMID- 8010017 TI - [Determination of gelsemium alkaloids by RP-HPLC]. AB - Gelsemium elegans Benth is a kind of traditional Chinese medicine, eight alkaloids have been isolated from this herb. In recent years, an HPLC method for the separation and determination of five of these alkaloids, ie. gelsemium A (G), koumine (F), kumantenidine (D), kumantenine (B) and kumantenmine (A) is described, dichroine being used as the internal standard. In this report a RP column of C18 and the mobile phase methanol--water--n-butylamine (78:22:0.1 V/V) were employed. The flow rate was 1.0 ml/min, the column temperature was 25 degrees C and the detection wavelength was 256 nm. The calibration curves showed good linearity over the range of 0.02-0.12 microgram, r = 0.9835-0.9977 and the recoveries were 95.01-99.70% for the five alkaloids. The method is simple, sensitive and reproducible and can be used for the quality control of Gelsemium preparations for clinical evaluation. PMID- 8010018 TI - [The spectroelectrochemical characterization of electrochemical oxidation mechanism of vitamin E]. AB - The electrochemical oxidation mechanism of vitamin E(VE) on pyrolytic graphite electrode (PGE) was studied by cyclic voltammetry. The results of experiment showed that the oxidative mechanism of VE was a quasi-reversible ECE process controlled by diffusion on PGE and the same on platinum electrode (PtE). The results of absorption spectroelectrochemistry experiment verified the oxidative mechanism of VE. It is clear that the oxidation of VE is a quasi-reversible 2e process to a divalent cation and followed by hydrolysis reaction to the quinone or semi-quinone compounds in acidic solution. PMID- 8010019 TI - [Study on analysis of peimisine in bulbus fritillariae by HPLC]. AB - A new method for the determination of peimisine in bulbus Fritillariae by ion pair HPLC has been developed. The chromatographic system consists of ODS column and mobile phase of methanol--water (69:31) containing 7.5 mmol/L of SDS (pH 4.5 +/- 0.1). Twelve samples of different species in the family of Fritillaria have been analyzed by this method. The results show that all samples contain peimisine and the contents of peimisine are correlative to those of total alkaloids. PMID- 8010020 TI - [Determination of pseudoephedrine in human plasma by gas chromatography with a mass selective detector (GC-MSD)]. AB - A specific and sensitive method has been established for the analysis of pseudoephedrine (PE) in human plasma by gas chromatography with a mass selective detector (GC-MSD). PE and ephedrine (E, internal standard) reacted with trifluoroacetic anhydride (TFAA) and the derivatives were separated by a HP-5 capillary column. PE-TFA and E-TFA were quantitatively measured by selected ion monitoring (m/z = 154). The detection limits for E and PE were 1 ng/ml plasma. The recoveries were about 99%. PMID- 8010021 TI - [Study on dissolution test in vitro and bioavailability of oral osmotic pump of verapamil hydrochloride]. AB - This paper deals with the evaluation of osmotic pump of verapamil hydrochloride tablet (C) by measuring in vitro/in vivo test. The results showed that the dissolution behaviors were of zero-order kinetic and release constant in vitro (Kr) of C was 9.9450. The plasma levels of Ver.HCl in eight volunteers following single and multiple oral doses of these dosage forms were determined using HPLC method. The pharmacokinetic parameters were fitted by nonlinear least square method with a computer on the basis of two-compartment model. The pharmacokinetic parameters of Cmax, Tmax, t1/2, Ka, K10 and K21 were calculated. The bioavailability of tablet C relative to B and A was 101.7%, 96.16% respectively. A significant correlation was found between in vitro dissolution and in vivo absorption. PMID- 8010022 TI - Enhancement of cardiac performance of isolated working guinea pig heart by rabbit platelet and involvement of histamine. AB - Alterations of cardiac performance by washed rabbit platelets were investigated in isolated working guinea pig hearts. Enhanced cardiac functions emerged about 5 s after intracardiac injection of platelet suspension (6 x 10(8)-10 x 10(8) cells.ml-1). The LVP, +dP/dtmax, -dP/dtmax, and HR were increased by 30%, 73%, 46%, and 13% (P < 0.05 or 0.01), respectively, and recovered about 10 min later. In the range of 1 x 10(8)-70 x 10(8) cells.ml-1, platelet suspension strengthened the cardiac performance in a concentration-dependent manner. The supernatant demonstrated positive inotropic and chronotropic effects as well, quite similar to those of the suspension. Cimetidine (Cim, 1 mumol.L-1) reduced the cardiotonic effect of the platelet. Mast cell of the isolated guinea pig heart was proven to be in activated state upon 10(9) cells.ml-1 platelet challenge by electron microscopy. Histamine content in platelet suspension measured by HPLC was shown to be 2.6 +/- s 0.7 microgram per 10(9) platelets. It is concluded that histamine, released from platelets and cardiac mast cells, was a key factor in the cardiac alterations. PMID- 8010023 TI - Chlorpromazine attenuated electroacupuncture analgesia in conscious rabbits. AB - By measuring the defense behavior in response to the noxious stimulation induced by potassium iontophoresis on ear-lobe skin of conscious rabbit, chlorpromazine (CPZ) (0.5 mg.kg-1, i.v.) induced hyperalgesia, whereas it significantly attenuated electroacupuncture analgesia (EAA) efficacy. Monoamines and their metabolites in cerebrospinal fluid (CSF) were measured by high pressure liquid chromatography with electrochemical detector (HPLC-ECD) while the attenuation effect of CPZ on EAA was observed. CPZ markedly enhanced 3,4 dihydroxyphenylacetic acid (DOPAC) (P < 0.05) and homovanillic acid (HVA) (P < 0.01) contents in CSF both in the presence and absence of electroacupuncture. CPZ attenuated EAA with elevations of either DOPAC or HVA concentrations in CSF. There was a positive correlation between the increase of DOPAC or HVA content in CSF and the attenuation effect of CPZ on EAA (P < 0.05). These results suggested that the activation of dopamine system was unfavorable for EAA. PMID- 8010025 TI - Effects of tetrandrine on free intracellular Ca2+ in isolated rat brain cells. AB - Using Ca(2+)-sensitive fluorescent indicator, Fura-2/AM, intracellular free Ca2+ ([Ca2+]i) was measured. Resting [Ca2+]i was 221 +/- 18 nmol.L-1 in the presence of Ca2+ 1.3 mmol.L-1 in Hank's solution. Tetrandrine (Tet) 30 mumol.L-1 had no effect on the resting [Ca2+]i when the extracellular Ca2+ were 0-2 mmol.L-1. In the presence of extracellular Ca2+ 1.3 mmol.L-1, Tet (1-100 mumol.L-1) concentration-dependently inhibited the high extracellular K(+)-induced [Ca2+]i elevation, with an IC50 value of 8.2 mumol.L-1 (95% confidence limits: 1.9-32.9 mumol.L-1). Low concentrations of Tet (1-10 mumol.L-1) did not alter the norepinephrine-induced [Ca2+]i elevation. Tet 30 mumol.L-1 depressed norepinephrine 10 mumol.L-1 induced [Ca2+]i elevation by 42%. The results suggested that Tet inhibited the Ca2+ influx through voltage-dependent ionic channels and, at high concentrations, through receptor-operated ionic channels in the brain cells. PMID- 8010024 TI - Effects of hydrogen peroxide on membrane fluidity and Ca(2+)-transporting ATPase activity of rabbit myocardial sarcoplasmic reticulum. AB - This study was to investigate the effects of hydrogen peroxide on membrane fluidity and Ca(2+)-ATPase activity of rabbit myocardial sarcoplasmic reticulum (SR). The membrane fluidity of SR was monitored by measuring the changes in the steady state fluorescence anisotropies (rs) using diphenylhexatriene as a probe. The Ca(2+)-ATPase activity was determined by assaying the amount of inorganic phosphate (Pi) released from ATP. It was found that the membrane fluidity (rs: 0.154 +/- 0.014 vs 0.113 +/- 0.010, P < 0.01) and Ca(2+)-ATPase activity (3.1 +/- 1.3 vs 25.3 +/- 2.4 mumol Pi.h-1/mg protein, P < 0.01) were reduced in SR exposed to H2O2 (2 mmol.L-1) for 40 min. Catalase 20 micrograms.ml-1 completely prevented the SR damages caused by H2O2. H2O2 jeopardized the SR in a concentration- and time-dependent manner as measured by changes in rs values and Ca(2+)-ATPase activities, which were negatively correlated (r = 0.981, P < 0.01). These results suggest that H2O2 produces dysfunctions of the rabbit myocardial SR, and that the alteration of membrane fluidity may be one of the mechanisms responsible for the decrease of Ca(2+)-ATPase activity. PMID- 8010026 TI - Effects of ginseng root saponins and ginsenoside Rb1 on immunity in cold water swim stress mice and rats. AB - The proliferation of splenic lymphocytes, the humoral immune response to sheep red blood cells, and the phagocytotic function of intraperitoneal macrophages were all suppressed by cold water (4 degrees C) swim stress (CWSS) for 5 min in rats and for 3 min in mice. Meanwhile, the levels of serum corticosterone increased. Ginseng root saponins 100 mg.kg-1 or ginsenoside Rb1 10 mg.kg-1 ip or ig completely antagonized the immunosuppression induced by CWSS, and inhibited the increase of serum corticosterone in CWSS rats, but increased the level of serum corticosterone further in CWSS mice. PMID- 8010027 TI - Effects of m-nifedipine on dihydropyridine binding sites in cardiac and cerebral cortex cell membranes from left ventricular hypertrophied rats. AB - m-Nifedipine (m-Nif 20 mg.kg-1.d-1 ig for 9 wk) decreased left ventricular weight in the renovascular hypertensive rats (P < 0.01). Though not significantly affecting the density of dihydropyridines (DHP) receptor (Bmax), m-Nif administered whether for prevention (6 wk postclipping) or for regression (9 wk postclipping), markedly decreased the total number of DHP binding sites in hypertrophied left ventricle (LV). m-Nif also reduced the dissociation constant (Kd) of DHP binding sites in the membranes of LV and cerebral cortex from cardiac hypertrophied rats (P < 0.01). These effects of m-Nif were similar to those of nifedipine (Nif) in the same dosage. The results suggest that m-Nif can prevent and regress the LV hypertrophy resulted from renovascular hypertension and reduce the total number of DHP binding sites in the membranes of LV from cardiac hypertrophied rats. PMID- 8010028 TI - Effects of hydrochlorothiazide on contraction and 86Rb efflux in rat aorta. AB - Hydrochlorothiazide (HCT) (0.1, 0.3 mmol.L-1) inhibited the contraction of rat aortic strips induced by low (< 40 mmol.L-1), not higher concentrations of KCl. HCT (0.3 mmol.L-1) did not inhibit the CaCl2-induced contraction of the aortic strips depolarized with high K+ (KCl 80 mmol.L-1). The inhibitory effect of HCT (0.1 mmol.L-1) on KCl (20 mmol.L-1)-induced contraction was markedly antagonized by BaCl2 (0.1 mmol.L-1) and tetraethylammonium (TEA) (0.3 mmol.L-1), but not by glibenclamide (Gli, 0.01 mmol.L-1). With norepinephrine (NE) or 5-HT as agonists, HCT (0.3 mmol.L-1) also inhibited the contractions of rat aortic strips. In the 2 components of NE-induced contraction, HCT inhibited only the tonic component depending on Ca2+ influx, but not the phasic component elicited by the release of intracellular Ca2+. The inhibitory action of HCT was endothelium-independent. That the HCT (3 mmol.L-1) increased the 86Rb efflux rate coefficient was antagonized by BaCl2 (0.1 mmol.L-1), but not by Gli (0.01 mmol.L-1). The results indicated that the inhibitory effect of HCT on the contraction of rat aorta was attributable to the opening of membrane potassium channels. PMID- 8010029 TI - Electrophysiological effects of N6-cyclopentyl-adenosine and [-]-N6 [phenylisopropyl]-adenosine on pacemaker cells in sinoatrial node of guinea pigs. AB - The electrophysiological effects of N6-cyclopentyladenosine (CPA) and [-]-N6 [phenylisopropyl]adenosine (R-PIA) (both are selective adenosine A1 receptor agonists) on pacemaker cells in sinoatrial (SA) node of guinea pigs were investigated using intracellular microelectrodes. CPA and R-PIA increased the amplitude of action potential, amplitude of the maximal diastolic potential and maximal rate of depolarization (phase 0), but decreased the velocity of diastolic (phase 4) depolarization, the rate of pacemaker firing, and the duration of 90% repolarization in pacemaker cells of guinea pigs. 8-Phenyltheophylline (a nonselective antagonist of adenosine receptors) and glibenclamide (a potent blocker of ATP-sensitive K+ channels) inhibited the electrophysiological responses of pacemaker cells to CPA. These results suggest that the electrophysiological changes induced by CPA are adenosine receptor-dependent and mainly mediated by activation of ATP-sensitive K+ channels coupled to adenosine receptors. PMID- 8010030 TI - [Effects of morphine on sensitivities of alpha-adrenoceptors in toad spinal ganglion neurons]. AB - Intracellular recordings were performed on 35 neurons from 35 isolated toad spinal ganglia (SG) and the extracellular free calcium ion activities were measured in another 26 isolated toad SG by Ca(2+)-selective microelectrodes. The effects of morphine on the sensitivities of alpha-adrenoceptors were observed. It was found that depolarization of membrane potential induced by norepinephrine (NE 10-100 mumol.L-1) or alpha 1-adrenoceptor agonist phenylephrine (100 mumol.L-1) was depressed by morphine (27 mumol.L-1). Superfusing SG with opioid receptor antagonist naloxone (100 mumol.L-1) blocked the depressing effect of morphine on NE-induced depolarization. The depressing effect of morphine on NE-induced depolarization was not affected by superfusing SG with alpha 2-adrenoceptor antagonist yohimbine (5 mumol.L-1). NE (100 mumol.L-1) reduced the extracellular free calcium ion activity while morphine (27 mumol.L-1) increased the extracellular free calcium ion activity in SG. It is concluded that morphine down regulates the sensitivity of alpha 1-adrenoceptor in toad SG neuron mediated by opioid receptor and the variation in Ca2+ activity may be involved in this effect. PMID- 8010032 TI - [Effect of salidroside on cultured myocardial cells anoxia/reoxygenation injuries]. AB - The effects of salidroside (p-hydroxyphenethyl glucoside, Sal, first isolated and synthesized in China) on reoxygenation damages were studied on cultured myocytes from neonatal rat hearts. At least 80% of cells in the form of monolayer contracted spontaneously on cultured 72 h, then the cells were used in the contractility experiment. After anoxia 3 h and reoxygenation for 1 h the beating of myocardial cells was slowed down and the lactate dehydrogenase (LDH) liberated by myocardial cells was increased. Electron microscopy of myocardial cells revealed localized defects of cell membrane, dilatation of endoplasmic reticulum, and swelling of mitochondria. One h before anoxia, addition of Sal 10 and 30 micrograms.ml-1 increased the beat rate of myocardial cells, depressed the release LDH of from myocytes, and the myocardial ultrastructure was normal during anoxia and reoxygenation. Hence Sal may provide some protective effects on the anoxia/reoxygenation damages upon myocardium. PMID- 8010031 TI - [Effects of morphine on muscarinic receptors in limbic system in acute adjuvant induced arthritic rats]. AB - To induce arthritis, the adjuvant with heat-killed Mycobacterium tuberculosis was injected into the ankle joint in rats. Local redness, swelling, hotness, pain, and motor dysfunction of the inflamed joint (as well as mental dullness) were observed 48 h after inoculation. At this time, the maximal binding capacity (Bmax) of muscarinic receptors in limbic system was increased, while the dissociation constant (Kd) was unchanged. Injection of morphine (5 mg.kg-1) 3 times within 48 h after the inoculation resulted in a decrease of Bmax and an increase of Kd of M-receptors, together with diminution of pain and disappearance of dullness. PMID- 8010033 TI - [Protection of mexiletine against hypoxic damage of synaptic function in hippocampal slices]. AB - The evoked population spike (PS) and presynaptic fiber volley (PV) were recorded from the CA1 area in rat hippocampal slices. At the 3rd min of hypoxia, the amplitude of PS declined to 0.4 +/- 0.4 mV in control slices whereas to 1.2 +/- 1.2 mV or 1.5 +/- 0.4 mV in slices pretreated for 1 h with mexiletine (Mex) 10 or 100 mumol.L-1, respectively. Thirty min after reoxygenation the amplitude of PS recovered to 11.1% of its original level in control slices, but to 47.6% or 65.0% in slices pretreated with Mex 10 or 100 mumol.L-1 respectively. Thus Mex retarded the hypoxic declining of PS during hypoxia and accelerated the recovery of PS during reoxygenation. At normal conditions Mex 100 mumol.L-1 reversibly reduced the amplitude of PS and PV partially. Our results suggested that the inhibition of Mex on sodium current may play an important role in the mechanism of its protection against hypoxic damage. PMID- 8010034 TI - [Effects of sennosides on cellular electric activities in smooth muscle cells of guinea pig taenia coli]. AB - The effects of sennosides (Sen, an extract of Chinese rhubarb) on cellular spontaneous electric activities of guinea pig taenia coli were studied by intracellular microelectrode technique. Sen 0.1-20 mmol.L-1 improved the depolarization of cell membrane, quickened the burst of slow wave potential, and increased notably the frequency of spike potentials. Sen (20 mmol.L-1) induced spontaneous spike potentials. These results provide direct evidence for the enhancing effect of Sen on intestinal peristalsis at cellular level. PMID- 8010036 TI - [Antifertility effects of mifepristone and epostane alone and in combination in rats]. AB - A complete interceptive action on pregnancy was shown after ig mifepristone (RU 486) 16 mg.kg-1 or epostane 96 mg.kg-1 on d 10 of pregnancy in rats. The ig ED50 (95% fiducial limits) of RU-486 when given alone and in combination with epostane 12 mg.kg-1 were found to be 7.8 (5.3-10.0) and 2.6 (2.0-3.3) mg.kg-1, respectively (P < 0.05), while those of epostane when given alone and in combination with RU-486 4 mg.kg-1 were 25.5 (19.4-33.6) and 5.6 (4.7-7.4) mg.kg 1, respectively (P < 0.05). An absorption promotor, sodium dodecyl sulfate 24 mg.kg-1 ig, when given in combination with RU-486 8 mg.kg-1 or epostane 24 mg.kg 1, induced complete interceptive action on pregnancy. Levels of plasma progesterone declined significantly when epostane 12 mg.kg-1 was given in combination with RU-486 4 mg.kg-1 as compared with epostane 12 mg.kg-1 alone (P < 0.05). Results showed that drug combination therapy was of benefit both to RU-486 and epostane in their interceptive actions. PMID- 8010035 TI - [Pharmacokinetics of moracizine and moracizine sulfoxide in healthy volunteers]. AB - The pharmacokinetics of moracizine (Mor) and moracizine sulfoxide (Mor-SO) determined by reversed phase HPLC was reported. The data in 6 volunteers after a single oral dose (600 mg) showed an one-compartment open model. The peak concentration in plasma (2.1 +/- 0.4 micrograms.ml-1) of Mor reached within 1-2 h. The Mor-SO concentration in plasma was much lower (0.19 +/- 0.06 micrograms.ml 1) than that of Mor, but its elimination T1/2 (2.3 +/- 1.0 h) was similar to that of Mor (1.5 +/- 1.0 h). The recoveries of Mor, Mor-SO, moracizine sulfone (Mor SO2) in urine within 48 h were 0.07%, 0.25%, and 0.06% of the total dose, respectively. The Mor and Mor-SO concentration ranges in plasma for 9 arrhythmic patients after 2-wk therapeutic trial were 0.09 +/- 0.07 to 0.9 +/- 0.5 microgram.ml-1 and 0.040 +/- 0.023 to 0.15 +/- 0.06 micrograms.ml-1, respectively. These results suggested that cumulative doses would not result in accumulation of the drug and the anti-arrhythmic effect of Mor-SO might not be realized. PMID- 8010038 TI - [Effect of cholecystokinin and its antagonists lorglumide, devazepide, and L 365,260 on gastrointestinal motility in rats]. AB - Cholecystokinin (CCK) plays an important role in gallbladder contraction and gut motility. Sincalide (CCK-8) evoked guinea pig isolated ileum contraction at 10( 5)-10(-1) mumol.L-1 in a concentration-dependent manner, EC50 being 207 pmol.L-1. It delayed the gastric emptying as well. The rate of inhibition of gastric emptying was 71 +/- 12% at 100 micrograms.kg-1 by ip. Sincalide antagonists: lorglumide, devazepide, and L-365,260 antagonized the ileal smooth muscle response to sincalide in a concentration-dependent manner. Their pA2 were 7.30, 10.02, and 7.77, respectively. Lorglumide, devazepide, and L-365,260 inhibited the delaying of gastric emptying evoked by sincalide. The IC50 were 0.11, 0.0064, and 0.66 mg.kg-1, respectively. PMID- 8010037 TI - [Effect of spermidine on uptake of chloroquine by Plasmodium berghei]. AB - To probe into the effect of spermidine on chloroquine (Chl) uptake by P berghei and its role of Chl-resistance, mice infected with Chl sensitive strain (CS) of P berghei were given Chl 20 mg.kg-1 ig combined with spermidine (Spe) 42 mg.kg-1 ip. It was found that 3 and 16 h after combined administration, Chl quantity uptaken by the parasites was reduced respectively by 59.6% and 53.8% in comparison with that in the Chl group. However, there was no difference in parasitaemia between Chl group (2.3 +/- 1.0) and Chl-Spe group (1.7 +/- 1.0), whereas the untreated control group remained a parasitaemia of 36 +/- 9. The authors deemed that Chl resistance is not merely attributed to the insufficient quantity of Chl in the Chl resistant parasites, the change in the sensitivity to Chl of Chl resistant parasites and the role of Spe in Chl resistance production should also be taken into consideration. PMID- 8010039 TI - [Inhibitory effects of protein kinase C inhibitor and calmodulin antagonist on tumor necrosis factor production by mouse macrophages]. AB - Mouse peritoneal macrophages were primed with calcium ionophore calcimycin 1 mumol.L-1 for 8 h and then elicited by lipopolysaccharides (LPS, 10 ng.ml-1) for 6 h to induce tumor necrosis factor (TNF), measured by crystal violet staining assay using murine fibroblast L929 cells. Protein kinase C (PKC) inhibitor, 1-(5 isoquinolinesulphonyl)-2-methylpiperazine (H-7) and calmodulin (CaM) antagonist, N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide (W-7) were studied on LPS induced TNF production by macrophages. Addition of H-7 (0.31-50 micrograms.ml-1) and W-7 (10-4000 ng.ml-1) simultaneously with LPS to the culture medium suppressed LPS-induced TNF production in a concentration-dependent manner. When macrophages were pretreated with W-7 (10 ng.ml-1), LPS-induced TNF production was completely inhibited at 8 h. These results suggest that TNF production by macrophages may be dependent on the PKC and CaM. PMID- 8010040 TI - [Effect of nifedipine on contractive motility and ciliary ultrastructure of rabbit fallopian tube]. AB - The effects of nifedipine (Nif) on the motility of isolated isthmus of rabbit Fallopian tube were studied in comparison with those of verapamil (Ver) and cinnarizine (Cin). Nif (0.01 mumol.L-1), Ver (0.03 mumol.L-1), and Cin (3 mumol/L 1) inhibited the spontaneous contraction, and the contraction caused by norepinephrine (NE). The pD'2 values of Nif, Ver, and Cin were 6.86, 6.13, and 4.43, respectively. Moreover, both Nif and Ver delayed the ovum transport through the Fallopian tube 48 h after iv chorionic gonadotropin (HCG). Nif did not modify the ultrastructure of the ampulla ciliary microtubule, but it influenced the mitochondrial structure and caused an irregular ciliary motion. PMID- 8010041 TI - [Antiviral activity of mangiferin against herpes simplex virus type 2 in vitro]. AB - The effect of mangiferin, a tetrahydroxy pyrrolidone saponin extracted from the leaves of mango (Mangifera indica), against herpes simplex virus type 2 (HSV-2) in vitro was studied. The 50% effective concentration (EC50) of it against HSV-2 plaque formation in HeLa cells was 111.7 micrograms.ml-1, and the concentrations of 33 and 80 micrograms.ml-1 reduced the virus replicative yields by 90% (EC90) and 99% (EC99), respectively. The therapeutic index (IC50/EC50) was 8.1. Mangiferin did not directly inactivate HSV-2. The results of the drug addition and removal tests suggest that mangiferin inhibits the late event in HSV-2 replication. PMID- 8010042 TI - NMDA and non-NMDA receptors mediating nociceptive and non-nociceptive transmission in spinal cord of cat. AB - The effects of excitatory amino acid (EAA) receptor agonists and blockers on the nociceptive and non-nociceptive transmission in cat spinal dorsal horn neurons were studied. About 80% of neurons were facilitated by iontophoretic injection of EAA receptor agonists (10-100 nA), such as N-methyl-D-aspartate (NMDA), quisqualic acid (QA), kainic acid (KA), and DL-homocysteic acid (DLH). The nociceptive responses, irregular spontaneous discharges, and C afferent induced response of dorsal horn neuron, were reduced by the different EAA receptor blockers (35-150 nA), such as DL-2-amino-5-phosphono-valerate (APV), ketamine, 6,7-dinitro-quinoxaline-2, 3-dion (DNQX), and kynurenic acid (Kyn). Ketamine and Kyn had different effects on the long-lasting response and the short-lasting response of neurons induced by stimulation of A afferent fiber of the tibial nerve. The long-lasting response in 8/12 neurons was reduced by Kyn, but not by ketamine, and the short-lasting response was reduced by neither Kyn nor ketamine. The DLH-induced excitations were reduced by DNQX and, to a less extent, by APV. The results suggest that both NMDA and non-NMDA receptors are involved in spinal nociception; the non-nociceptive information is in part mediated by non-NMDA receptors. PMID- 8010043 TI - Midazolam pharmacokinetics and electroencephalographic changes in eight Chinese men. AB - Eight Chinese healthy male volunteers aged 27 +/- s 4 a were injected i.v. midazolam (Mid) 15 mg. Blood samples were collected at 0, 2, 5, 7, 10, 20, 30, 45, 60, 90, 120, 180, and 240 min. A HPLC method was established for determining the Mid concentrations in serum. The concentration-time data was fitted with biexponential curve. Pharmacokinetic parameters were: T1/2 alpha = 6.8 +2- 2.5 min, T1/2 beta = 118 +/- 27 min, Vc = 25 +/- 7 L, Cl = 393 +/- 79 ml.min-1, Vdss = 59 +/- 13 L, AUC0-infinity = 39.6 +/- 8.6 g.min.L-1. The electroencephalogram (EEG) showed a decrease in alpha activity and an increase in beta activity. The EEG pattern reverted toward baseline after 2-3 h. Pharmacokinetic and EEG findings suggest that Mid is a preferable anesthesia inducing agent. PMID- 8010044 TI - Characterization and distribution of mu opioid receptors in rabbit cerebellum. AB - The binding characteristics and distributions of [3H]ohmefentanyl ([3H]OMF), [3H]etorphine, [3H] N-methyl-N-[7-(I-pyrrolidinyl)-1-oxaspiro(4,5)dec-7-yl] benzeneacetamide [3H]U-69593), and [3H] (D-penicillamine2, D-penicillamine5) enkephalin ([3H]DPDPE) in rabbit cerebellum were studied. In saturation experiment, [3H]OMF bound to a single population of sites with Kd = 2.2 +/- 1.3 nmol.L-1 and Bmax = 69 +/- 13 fmol/mg protein. The results of [3H]etorphine (Kd = 1.0 +/- 0.4 nmol.L-1 and Bmax = 16 +/- 6 fmol/mg protein) were similar to those of [3H]OMF. There were no specific bindings of [3H]U-69593 and [3H]DPDPE in rabbit cerebellar membranes. In autoradiographic study, the gray scales of specific binding for [3H]OMF, [3H]etorphine, [3H]U-69593, and [3H]DPDPE were 20.2 +/- 4.6, 8.5 +/- 2.7, 2.0 +/- 0.7, and 3.2 +/- 4.3, respectively. The gray matter of rabbit cerebellum was intensely labeled by [3H]OMF and [3H]etorphine, but not by [3H]U-69593 or [3H]DPDPE. These results suggested that the rabbit cerebellum contained mu opioid receptors. PMID- 8010045 TI - Opioid, calcium, and adrenergic receptor involvement in protopine analgesia. AB - The analgesic effect of protopine (Pro), an alkaloid isolated from Papaveraceae, was confirmed by tail-pinch and hot-plate tests when given sc 10-40 mg.kg-1, and 20-40 mg.kg-1 inhibited the spontaneous movements of mice. Pro 40 mg.kg-1 increased the sleeping rate, prolonged the sleeping duration, and shortened the sleeping latency in mice hypnotized by ip pentobarbital sodium 30 mg.kg-1. Pro 10 40 mg.kg-1 did not affect the inflammatory reaction induced by xylene and egg white. An icv injection of Pro 20-200 micrograms/mouse showed a remarkable analgesic effect in mice. The icv pretreatment of naloxone 2 micrograms blocked the analgesic effect completely. CaCl2 40 micrograms/mouse (ICV) or methotrexate 10 mg.kg-1 (ip), an agonist of Ca2+ channel, showed a complete blockade of the analgesia, while nifedipine 100 mg.kg-1(po), a blocker of Ca2+ channel, enhanced the analgesic effect. The ip pretreatment of reserpine 4 mg.kg-1 reduced the Pro analgesia. Phentolamine 10 mg.kg-1(ip), an alpha-adrenergic blocker, tended to weaken the analgesia, but propranolol 10 mg.kg-1(ip), a beta-blocker, did not affect it. These results suggest that Pro displays its analgesic effect mainly through the opioid and calcium systems and partly through the adrenergic mechanism. PMID- 8010047 TI - Effects of quercetin on platelet and reperfusion-induced arrhythmias in rats. AB - The role of platelets in reperfusion arrhythmias (RA) and the efficacy of quercetin (Que) in preventing the arrhythmias were investigated in anesthetized rats. Platelet count (PC) was performed, the ultrastructure of platelets was scrutinized, and the levels of thromboxane B2 (TXB2) and 6-keto-prostaglandin F1 alpha (Keto-PGF1 alpha) in plasma were determined by radioimmunoassay (RIA). The pretreatment with Que (5 mg.kg-1) 2 min prior to reperfusion inhibited RA. Que remarkably improved the ultrastructural deviation of platelet, inhibited the platelet aggregation and thromboxane A2 (TXA2) formation, and increased the prostacyclin (PGI2) generation and the ratio of PGI2/TXA2. The decrease in PC and increase in TXB2 level in plasma indicated the participation of platelets in the arrhythmogenic activity of ischemia and reperfusion. The results showed that Que produced a protective effect against RA probably through inhibiting the platelet aggregation, TXA2 formation and increasing the PGI2 generation. PMID- 8010046 TI - Effects of direct lytic factors from southern Chinese cobra venom on Ca2+ movement in rabbit aorta strip. AB - The purified direct lytic factors (DLF) from southern Chinese cobra (Naja naja atra) venom induced a contractile response in Ca(2+)-free Krebs' solution and a further increase in the tension following a subsequent addition of Ca2+ into bath. After depletion of intracellular Ca2+ pool by phenylephrine, DLF failed to induce any contractile response. In 45Ca2+ experiments, DLF increased both 45Ca2+ release and 45Ca2+ influx. Procaine 2 mmol.L-1 decreased the DLF induced 45Ca2+ release and 45Ca2+ influx by 67 +/- 23% and 46 +/- 32%, respectively. Nifedipine and verapamil 1 mmol.L-1 markedly inhibited the contractile response and the 45Ca2+ influx induced by DLF. These results suggest that DLF induces extracellular Ca2+ entry through voltage dependent Ca2+ channel and Ca2+ release from the intracellular Ca2+ pool which is sensitive to phenylephrine. PMID- 8010048 TI - Cardiac electric activity of 1-(2-[(6-methoxyl)-naphthylmethyl])-1-methyl-N piperidinylacethyl-6,7- dimethoxyl-1,2,3,4-tetrahydroisoquinoline in SHR and WKY rats. AB - 1-(2-[(6-Methoxyl)-naphthylmethyl)])-1-methyl-N-piperidinylacethyl -6,7- dimethoxyl-1,2,3,4-tetrahydroisoquinoline (CPU-23), a substituted tetrahydroisoquinoline, reduced the voltages of P wave and J point, prolonged PR interval, and slowed sinus rhythm of ECG in spontaneously hypertensive rats (SHR) and age-matched normotensive WKY rats. The effects of CPU-23 on cardiac electric activity were stronger in SHR than in WKY rats (P < 0.05 or P < 0.01). The results suggest that CPU-23 have a calcium antagonistic activity on rat hearts and that calcium antagonists may exert a stronger inhibition of the cardiac electric activity in hypertensive rats than in normotensive rats. PMID- 8010049 TI - Anti-arrhythmic effects of captopril on coronary occlusion and reperfusion periods in pigs. AB - Anti-arrhythmic effects of captopril (Cap) were studied in the anesthetized pigs using a reversible balloon catheter. Results showed that Cap did not exert any influence on the weight percentage of ischemic area to the whole left ventricle, on the levels of serum creatine kinase (CK) and creatine kinase isozyme (CK-MB), nor on the incidence and duration of transient and persistent tachycardia, but reduced the incidence of ventricular fibrillation (2/12, 1/12 in high-dose group pigs treated with Cap 6 mg.kg-1 in the first 10 min, 25 micrograms.kg-1.min-1 in the later 90 min and 12/21, 11/21 in control group treated with normal saline through the occlusion and reperfusion periods, respectively, P < 0.05). It was suggested that Cap did not exhibit direct (or non-specific, if any) effects on anti-arrhythmias. PMID- 8010050 TI - Timed dose-response relationship of depressive action of ouabain on toad heart contraction in vitro. AB - Timed dose-response relationship (TDRR) of depressive action of ouabain (Oua) 0.01-30 mmol.L-1 on toad heart contraction in vitro was studied by simultaneous recordings of mechanical tension and electrocardiography. It was found that the inhibition of contraction tension, the latency, the half equilibrium time of depression, and the cardioplegia time (CPT) were all concentration-dependent (P < 0.01). The EC50 +/- L95 of Oua was 35 +/- 8 mumol.L-1, in which L95 is the average 95% confidence limit. The TDRR data of latency or CPT were fitted to the hyperbolic 4-parameter model II weighted with the square of SE inversely: Y = 25.9492(7.2757)/(1nX + 23.5906)(6.2757) + 72.7732 for latency and Y = 20637.37/(1nX + 3.0947)(3.5907) + 196.7069 for CPT. It was concluded that the hyperbolic type of TDRR was present in Oua depressive action on the toad heart contraction in vitro. PMID- 8010051 TI - Effects of bretylium tosylate on electrophysiologic properties of normal and digitalized papillary muscles of guinea pigs. AB - The effects of bretylium tosylate (BT) on the electrophysiologic properties of normal and digitalized papillary muscles isolated from guinea pigs were studied with regular glass microelectrode. BT prolonged effective refractory period (ERP) and action potential duration (APD) of normal papillary muscles. The ERP and APD of papillary muscles were shortened by perfusion with ouabain (Oua) 0.2 mumol.L 1. No recovery was seen in perfusion without drug for 30 min. In digitalized papillary muscles with Oua, ERP, APD90, and APD50 were prolonged by BT 120 mumol.L-1 form 175 +/- 20, 187 +/- 20, and 146 +/- 21 ms to 222 +/- 21, 220 +/- 19, and 190 +/- 19 ms, respectively. The results demonstrated that BT can prolong ERP and APD of papillary muscles digitalized with Oua. PMID- 8010052 TI - Effects of tetrandrine on functions and ultrastructure of alveolar macrophages in smoke inhalation-injured rabbits. AB - A rabbit model with severe smoke inhalation injury was used to explore the effects of tetandrine (Tet) on the release of inflammatory mediators and the level of [Ca2+]i in alveolar macrophages (AM) as well as on the ultrastructural changes. It was found that Tet reduced the number of white blood cells (WBC) in bronchoalveolar lavage fluid, inhibited the release of LTB4 and O2-. from AM, and increased the [Ca2+]i in AM. The changes in size, pseudopod, and lysosome evacuation in AM treated with Tet were smaller than those in the AM from the untreated. These results suggest that Tet may alleviate the pulmonary injury through inhibiting the activation of AM. PMID- 8010053 TI - Early treatment of schistosomal infection with praziquantel in mice. AB - The first single dose of praziquantel (Pra) was given ig to mice on the day of infection with Schistosoma japonicum cercariae, or 7 d, 14 d, and 21 d after infection. Afterwards, the same dose of Pra was given once at 1-3 wk intervals for 2-3 times. The prophylactic effect was estimated by the reduction of average number of total and female worms, the number of mice without female worm, and the gross change of the liver. When mice were treated with Pra 300-500 mg.kg-1 initially on d 21 after infection and repeated once every 1-2 wk for 2-3 times, almost all the female worms lodged in the host were killed, showing that either the host was protected from the infection of schistosomes or a great decrease in the intensity of the infection resulted. PMID- 8010054 TI - Effect of dose of metoprolol on its elimination by isolated perfused rat liver in vitro. AB - The effects of dose of metoprolol (Met) on hepatic elimination was studied in isolated rat liver perfused at a flow of 25 ml.min-1. The results showed that Met was eliminated by rat liver in accordance with one-compartment model. Linear kinetic eliminating processes (apparent first-order kinetics) were found in doses of Met 0.2, 0.5, 1.0, and 2.0 mg, T1/2 were 8.3, 8.8, 9.6, and 10.6 min and the clearance rate were 11.7, 11.8, 9.6, and 8.6 ml.min-1, respectively. Nonlinear eliminating processes were found in doses of Met 4, 8, and 12 mg. Vm and Km were 0.98, 1.05, and 0.94 microgram/min-1.ml-1 and 15.6, 16.9, and 14.6 micrograms.ml 1, respectively. It is concluded that hepatic Met elimination is independent on lower doses, but rested upon high doses. PMID- 8010055 TI - Antitumor activity and tumor necrosis factor production of Phytolacca acinosa polysaccharides I in mice. AB - The antitumor activities of Phytolacca acinosa polysaccharides I (PAP-I) and its effects on the induction of tumor necrosis factor (TNF) and immunological cytotoxicity of peritoneal macrophages were studied. PAP-I was given ip 5-20 mg.kg-1.d-1 x 7 d to ICR mice as priming agent with subsequent lipopolysaccharides (10 micrograms/mouse) iv for TNF production. TNF activity was measured by crystal violet staining assay using L929 cells. PAP-I showed priming activity for TNF production with hepto-splenic hyperplasia in a dose-dependent manner. The peritoneal macrophages treated with PAP-I 10 and 20 mg.kg-1 showed 67 and 74%, respectively, cytotoxicity (the control 34% cytotoxicity) against Meth A cells at effector:target = 40:1. PAP-I 10 and 20 mg.kg-1 prolonged the survival time of mice bearing ascites Meth A tumor from 21 +/- 4 to 32 +/- 10 and 38 +/- 8 d and inhibited the solid Meth A tumor growth with inhibition rate of 28.5 and 55.7%, respectively. These results suggested that the antitumor activities of PAP I were based on the activation of macrophages and induction of TNF. PMID- 8010056 TI - Inhibition of phosphorylation of histone H1 and H3 induced by 10 hydroxycamptothecin, DNA topoisomerase I inhibitor, in murine ascites hepatoma cells. AB - Hydroxycamptothecin (HCPT), isolated from Camptotheca acuminata, is a powerful antitumor alkaloid. Previous studies indicated that the molecular target of this agent was DNA topoisomerase I. The present results demonstrated that in vitro treatment of murine ascites hepatoma cells with HCPT resulted in a marked reduction in DNA syntheses and the inhibition of phosphorylation in histone was in a time-dependent manner. Gel electrophoresis found that HCPT had a selectively inhibitory effect on the phosphorylation of histone H1 and H3, but less effect on the other kinds of histones. In vivo, HCPT also exhibited a suppressive effect on histone H1 and H3 phosphorylation. These data suggested that HCPT-induced cell killing may be, at least in part, associated with the suppression of histone H1 and H3 phosphorylation. PMID- 8010057 TI - Effect of esculentoside H on release of tumor necrosis factor from mouse peritoneal macrophages. AB - Effect of esculentoside H (EH) on release of tumor necrosis factor (TNF) from murine peritoneal macrophage (Mphi) in vitro was studied. The results showed that EH (12.5-200 micrograms.ml-1) induced the thioglycolate-broth elicited peritoneal Mphi to release TNF into supernatants in a dose-dependent manner, and higher levels of TNF activity were detected in the supernatants from EH-stimulated calcimycin-primed Mo culture. EH-induced TNF release had a different type of kinetics compared with that of lipopolysaccharides (LPS). LPS-induced release of TNF increased rapidly until 6 h after LPS stimulation, then declined gradually, while EH-induced TNF release increased gradually after EH stimulation and reached its peak at approximately 24 h later. These results suggested that the anti-tumor mechanisms of Phytolaccaceae may be related to the capacity of EH for TNF release. PMID- 8010058 TI - Fate of methotrexate albumin microspheres after hepatic intra-arterial injection in dogs. AB - Methotrexate (MTX) albumin microspheres (40 microns) were injected into dog hepatic artery. The MTX levels in the hepatic vein maintained at relatively high concentration for over 3 h, whereas in the case of conventional MTX in saline the drug level decreased sharply soon after injection. After ia MTX in microspheres the MTX levels in liver were higher than those after MTX in saline. The microsphere emboli were entrapped in the hepatic precapillary arterioles. Thrombi were found in hepatic arterioles, with microsphere constituting the core. Hence MTX microspheres hepatic intra-arterial injection may be an effective treatment for patients with liver neoplasms. PMID- 8010059 TI - Antitumor activity and immuno-potentiating actions of Achyranthes bidentata polysaccharides. AB - Achyranthes bidentata polysaccharides (ABP), isolated from the root of Achyranthes bidentata Blume, 50 mg.kg-1 ip or 250 mg.kg-1 to ICR mice inhibited the growth of sarcoma 180. ABP 50 and 100 mg.kg-1 ip prolongated the survival days of mice bearing Ehrlich carcinoma. ABP 50-800 micrograms.ml-1 did not exert direct cytotoxic effect in vitro on S180 cells, but enhanced the cytotoxicity of peritoneal macrophages against S180 cells. ABP 50 mg.kg-1 ip x 17 d or 250 mg.kg 1 ig x 16 d promoted the plaque forming cells (PFC) response to sheep red blood cells (SRBC) and serum IgG level as well as splenocyte proliferation induced by mitogen Con A or LPS in tumor-induced immunodeficient mice. ABP also elevated the NK cell activity and serum TNF content in mice bearing S180. These results indicated that the antitumor effect of ABP may be related to its potentiating effect on both specific and nonspecific host immunological responses. PMID- 8010060 TI - Synergistic effect of oridonin and cisplatin on cytotoxicity and DNA cross-link against mouse sarcoma S180 cells in culture. AB - Oridonin (Ori) is an active principle isolated from Rabdosia rubescens. The cytotoxic effect of the combination of Ori and cisplatin was tested by MTT [3 (4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide] colorimetric assay. IC50 of cisplatin to cultured S180 cells in 24 h was 9.38 micrograms.ml-1. When the cells were treated with cisplatin plus Ori 0.5 and 1 microgram.ml-1, the IC50 were 1/3.4 and 1/6.7, respectively, of that with cisplatin alone. Modified alkaline elution was used to detect the DNA interstrand cross-link and DNA protein cross-link in S180 cells induced by the 2 drugs. A greater amount of DNA cross-link was detected when the cells were treated with cisplatin plus Ori than with cisplatin alone (P < 0.05). After lysis by proteinase K, a reduction in DNA cross-link was seen, which suggested that the drugs could produce both kinds of DNA cross-link. PMID- 8010061 TI - [Specific curative effects of nitrosourea drugs on tumor cells with Mer- phenotype in Chinese]. AB - O6-Methylguanine DNA methyltransferase (O6-MT) activity and cellular sensitivity to nitrosourea drugs of 10 kinds of tumor cell strains derived from Chinese patients were measured by 3H radioactivity and colony-forming ability, respectively. The results in vitro showed that nimustine (Nim) 25 micrograms.ml-1 and carmustine (Car) 20 micrograms.ml-1 exhibited specific killing effects on Mer phenotype tumor cells characterized by low O6-MT activity. In vivo both Nim and Car (25 mg.kg-1.wk-1 x 4 wk, ip) had specific curative ability to Mer- tumor cells implanted in nude mice. These findings suggested that assay of O6- MT activity in tumor biopsy could be used as a predictable guide to human tumor chemotherapy with nitrosourea compounds. PMID- 8010062 TI - [Effect of targeting treatment of mitomycin C immunoconjugate on stomach neoplasm]. AB - An anti-gastric cancer monoclonal antibody MGb2-mitomycin C conjugate via dextran T-70 as intermediate (MGb2-PAD-MMC) was produced, and 28-30 g molecules of MMC were introduced into 1 g molecule of MGb2. Ninety-six hours after ip of 125I-MGb2 PAD-MMC (1.48 MBq/22 micrograms MGb2 per mouse) to nude mice bearing human gastric cancer SGC-7901, the tumor tissue:blood (T/NT) radioactivity ratio was 2.6, very much higher than that of the control 125I-normal IgG-PAD-MMC group (T/NT = 0.20). Single photo computed tomography imaging confirmed the results of biodistribution study. MGb2-PAD-MMC exhibited selective killing action on the SGC 7901 cells in vitro, which was considered to be mediated by monoclonal antibody MGb2. Nude mice inoculated with SGC-7901 xenograft in bilateral subrenal capsule were treated by MMC (ip), human recombinant interferon-alpha (Hu-IFN-alpha im), MGb2-PAD-MMC (ip) and MGb2-PAD-MMC+Hu-IFN-alpha daily for 5 d beginning 4 h after inoculation. The efficacy of the reagents estimated by the reduction of tumor size and calculated by T/C (%), was 28.3%, 16.4%, 47.8%, and 83.1%, respectively. These results demonstrated that the antitumor effect of MGb2-PAD-MMC was superior to free MMC, and that the Hu-IFN-alpha might further enhance the action of MGb2 PAD-MMC. PMID- 8010064 TI - [Prevention of sinomenine on isolated rat myocardial reperfusion injury]. AB - Acute myocardial ischemia and reperfusion injury of rats were produced by ligating the left coronary artery for 15 min and reopening. The myocardial calcium contents were increased from 3.53 +/- 0.58 mumol/g dry wt in sham operation group to 6.02 +/- 1.19 mumol/g dry wt with reducing SOD/MDA ratio and showing ventricular extrasystole (VE), ventricular tachycardia (VT), and ventricular fibrillation (VF). Sinomenine (Sin) and verapamil (Ver) infusion 15 min before ischemia attenuated the elevated calcium contents to the level of the sham operation group, increased SOD/MDA ratio, and produced antagonistic effects on VE, VT, VF. These improvements indicated that Sin, similar to Ver, prevented myocardial injury by lowering intracellular Ca2+ accumulation. PMID- 8010063 TI - [Characterization of a fluorouracil-resistant human gastric carcinoma cell line and its morphological behavior]. AB - A fluorouracil (FU)-resistant human carcinoma cell line (SGC-7901/R) was established in culture by progressively increasing the concentration of FU from 50 ng.ml-1 to 2.5 mg.ml-1. The cell line has been successfully subcultured for more than 150 passages during more than 2 years. Its degree of FU resistance was 139-fold vs that of FU sensitive cell line (SGC-7901/S), and the resistant phenotype was stable when cells were cultured for 23 passages in FU-free medium. The doubling time was 17.3 and 25.6 h for resistant cells and parental cells, respectively. Swiss (nu/nu) nude mice were used for the in vivo experiment, the FU-resistant cell line also exhibited resistance to FU and cross-resistance to mitomycin C. FU inhibited markedly the incorporation of [3H]UR into sensitive cells and only showed a 31.6% inhibition with FU 100 micrograms.ml-1 in resistant cells. For the incorporation of [3H]TdR into DNA, inhibitory rates were seen with different concentrations of FU in resistant cells. By morphologic observation, SGC-7901/R cells showed little secretion but without any tendency to glandular pattern. Their nuclei were allotype with enlarged perinuclear space and a few intranuclear pseudoinclusions. The mitotic phase of cells was found frequently. The phenotype of resistant cell line can be deduced more malignant than that of parental cell line. PMID- 8010065 TI - [Effects of 6,7-dimethoxycoumarin on experimental arrhythmia]. AB - By using the arrhythmic animal models, the effect of 6,7-dimethoxycoumarin (DMOC) on arrhythmia was investigated. The arrhythmia in anaesthetized rat were induced by iv aconitine 20 micrograms.kg-1 or CaCl2 5 mg.kg-1. The arrhythmia in anesthetized guinea pigs was induced by iv ouabain 3.6 micrograms.kg-1.min-1. Procainamide (PA) was used as a positive control. DMOC (33-500 mg.kg-1, ig) and PA (100-800 mg.kg-1, ig) in anaesthetized rats could delay the time of onset of arrhythmia induced by aconitine. The ED50 of DMOC and PA for postponing the occurrence of ventricular extrasystole (VE) were 88 mg.kg-1 (95% confidence interval was 43-165 mg.kg-1) and 183 mg.kg-1 (95% confidence interval was 109-304 mg.kg-1), respectively. The results suggested that the anti-arrhythmia potency of DMOC was higher than that of PA (P < 0.01). PMID- 8010066 TI - [Effects of scoparone on hemodynamics in anesthetized rabbits]. AB - The effects of scoparone (Sco), tetramethylpyrazine (TMP), and papaverine (Pap) on hemodynamics were compared in anesthetized rabbits. Three dosage levels (1.25, 2.5, 5 mg.kg-1, iv) were used for each agent. Sco lowered the blood pressure (BP), increased the cerebral blood flow (CBF) dose-dependently, but did not show significant influence on the femoral artery blood flow (FBF), the maximal decrease of BP, and the maximal increases of CBF being 15% and 20% of the control, respectively. In contrast, TMP raised the BP as well as increased the CBF and FBF simultaneously. Pap, however, lowered the BP, slightly increased the CBF and decreased the FBF only at large doses. The results suggested that Sco may cause a selective dilatation of cerebral blood vessels. PMID- 8010067 TI - [Effects of panaxadiol saponins isolated from Panax notoginseng on intracellular and extracellular calcium]. AB - Panaxadiol saponins (PDS) contain saponins Panax notoginseng B1 and E. The spontaneous beating induced by isoproterenol in isolated rat right atria and the increase of contractile force induced by Ca2+ in isolated guinea pig colon were inhibited by PDS 75 and 150 micrograms.ml-1, respectively and perhexiline 6.25 and 12.5 mumol.L-1, respectively. It suggested that PDS could block the potential dependent and receptor-operated calcium channel in smooth muscle. PDS 150 micrograms.ml-1 and perhexiline 6.25 mumol.L-1 depressed the contractile force induced by norepinephrine and Ca2+ in isolated rat aortic strips in Ca(2+)-free Krebs' solution. It suggested that PDS and perhexiline not only inhibited the release of intracellular Ca2+ but also blocked the inflow of extracellular Ca2+. PMID- 8010069 TI - [Inhibitory effects of psoralen plus ultraviolet irradiation on human leukemic cell lines]. AB - A semi-solid cell culture technique was used to study the sensitivity of K562, HL 60, and Raji leukemic cell lines to the inhibitory effect of psoralen plus ultraviolet irradiation. Results indicated that: 1) the inhibition rate of K562, HL-60, and Raji cell lines were 86%, 35%, and 36%, respectively; and 2) K562, HL 60, and Raji cell lines were treated with psoralen (20 micrograms.ml-1) for 1 h, then irradiated with ultraviolet (1 J/cm2) for 10 min, none of the leukemic cell lines showed colony or cluster formation. These suggested that the cytocidal effect of psoralen plus ultraviolet might be useful to eradicate the residual leukemic cells in the bone marrow transplantation. PMID- 8010068 TI - [Effects of m-nifedipine and nifedipine given intraduodenally on coronary flow, myocardial oxygen, and carbon dioxide metabolism in dogs]. AB - In anesthetized dogs intraduodenal administration of m-nifedipine (m-Nif) 0.4 mg.kg-1, coronary flow increased from 708 +/- 72 to 880 +/- 150 ml.min-1.kg-1 (+24%) at 5 min, to 1976 +/- 350 ml.min-1.kg-1 (+179%) at 30 min, and to 998 +/- 250 ml.min-1.kg-1 (+41%) at 4 h. At the dose of nifedipine (Nif), coronary flow increased from 778 +/- 91 to 1080 +/- 90 ml.min-1.kg-1 (+39%) at 3 min and to 1836 +/- 280 ml.min-1.kg-1 (+136%) at 90 min. m-Nif was more 43% potent than Nif and the duration of action of m-Nif was longer. m-Nif reduced heart rate by -39%, while Nif reduced only -11%. m-Nif increased coronary sinus O2 content and reduced MVO2, and no difference was seen between these 2 drugs. However, the rate of CO2 production with m-Nif was reduced to a greater degree than that of Nif. The results indicated that m-Nif was more beneficial in alleviating myocardial ischemia than that of Nif. PMID- 8010070 TI - [Effect of Phytolacca acinosa polysaccharides I on production of colony stimulating factors of mouse splenocytes in vitro]. AB - Phytolacca acinose polysaccharides I (PAP-I), M(r) = 10,000, activated mouse splenocytes to produce colony-stimulating factors (CSF) in vitro. The level of CSF was tested by [3H]TdR uptaken by bone marrow cells and rmGM-CSF was used as standard. PAP-I (10-500 micrograms.ml-1) increased CSF production of the splenocytes treated with or without concanavalin A. When the concentration of PAP I was 100 micrograms.ml-1, the level of CSF was about equivalent to that of rmGM CSF 11.8 +/- 1.8 ng.ml-1. After a 3-d incubation of PAP-I with the splenocytes, CSF was assayed. The longer the incubation, the higher were the CSF concentrations. The CSF type in supernants of splenocytes induced by PAP-I was determined by IL-3 McAb, GM-CSF McAb, and M-CSF PcAb. The type of CSF was found to be interleukin-3. PMID- 8010071 TI - [Effects of dimercaptosuccinic acid per os on copper excretion in rat]. AB - After dimercaptosuccinic acid (DMSA) was given intragastrically by gavage (ig) 0, 250, or 500 mg.kg-1 following in CuSO4 30 mg.kg-1 daily x 3 d in rats, the Cu contents of serum increased markedly within 1-12 h. When ig DMSA daily x 3 d, the excretion of Cu in urine per 24 h in the treated group was greatly promoted vs the control (P < 0.01), that in the 250 or 500 mg.kg-1 group were enhanced 2.4 3.8 and 5.8-7.8 times, respectively. That the excretion of Cu was increased in bile but not in feces suggested the plausible existence an enterohepatic circulation. PMID- 8010072 TI - [Effects of four drugs on intraerythrocytic Plasmodium yoelii of early and late stages]. AB - Erythrocytes of mice infected with Plasmodium yoelii of early stage (ESP) were separated from those infected with late stage (LSP), by a single density-gradient centrifugation in 19% diatrizoate meglumine. After centrifugation, the differential counts of ESP and LSP were 84.9% and 87.4%, respectively. The stage dependent effects of nitroquine (NQ), pyrimethamine (Pyr), perphenazine (Per) and metronidazole (Met) were studied with [3H]adenosine incorporation into ESP and LSP in vitro using chloroquine (CQ) as control. Like CQ, the 4 drugs inhibited that [3H]adenosine incorporation into LSP more remarkably than that into ESP. The IC50 of CQ, Met, Pyr, Per, and NQ against ESP were 1.89, 2.11, 2.56, 2.60, and 4.65 times as high as that against LSP, respectively. PMID- 8010073 TI - [Effects of paracetamol on glutathione S-transferase activity in mice]. AB - Paracetamol (acetaminophen) 90-150 mg.kg-1 increased the activity of serum glutathione S-transferase (GST) and yet reduced the activities of liver microsomal and homogenate GST in mice. The GST activity was dose- and time related to paracetamol. A negative correlation was found between serum GST and liver homogenate GST, as well as between serum GST and liver microsomal GST. A good positive correlation between serum GST and serum alanine aminotransferase (AAT) was also seen. In addition, butylated hydroxyanisole (BHA) and sodium ferulate (SF) remarkably reversed the changes of serum GST and serum AAT activities in paracetamol-treated mice. These results suggested that the conjugation level in liver was decreased in paracetamol-induced hepatotoxicity in mice. PMID- 8010074 TI - [Effects of Coriolus versicolor polysaccharides on productivity and longevity in Drosophila melanogaster]. AB - Coriolus versicolor polysaccharides (CVP), extracted from Coriolus versicolor (L) Fr, were composed of 67.53% beta-D-glucose, 12.49% D-mannose, 11.49% L-abequose, 8.21% D-galactose, and trace L-acofriose. On Oregon K stock of Drosophila melanogaster, 0.5%-5% of CVP increased the number of taking food. CVP 2%, 3%, and 5% increased the frequency of mating and 0.5%-3% increased the number of flies in first filial generation (F1). CVP (2% and 3% in mated test; 1% and 2% in unmated test) prolonged the mean lifespan, the maximal lifespan, and median lethal time (LT50) of female flies, but not male flies. PMID- 8010075 TI - [Free radical scavenging and antifatigue activities of Saussurea involucrata polysaccharides]. AB - The polysaccharides of Saussurea involucrata Kar et Kir was first isolated and identified by us. The polysaccharides scavenged superoxide anions by nitroblue tetraazolium colorimetric method with a median scavenging concentration of 22 micrograms.ml-1 and 95% confidence limit was 19.9-24.1 micrograms.ml-1. The polysaccharides inhibited the formation of thiobarbituric acid reaction substance in mouse liver homogenate and its IC50 was 2.3 mg/g fresh liver and 95% confidence limit was 2.05-2.55 mg/g fresh liver. By ip 25 mg.kg-1.d-1 x d in mice, the polysaccharides decreased oxygen consumption by 34.4% and ip same dosage x 6 d, the polysaccharide prolonged swimming time by 1.69-fold. PMID- 8010076 TI - [Inhibitory effects of cyproheptadine on calmodulin activated Ca(2+)-ATPase activity of rabbit erythrocyte membranes]. AB - Membranes prepared from rabbit erythrocyte hemolyzed in isosmotic imidazole (151 mmol.L-1, pH 7.4) buffer showed an enhancement of calmodulin (CaM) activated Ca(2+)-ATPase activity compared with the membrane prepared in hypotonic imidazole (10 mmol.L-1, EGTA 1 mmol.L-1, pH 7.4) buffer. The Ca(2+)-ATPase activity of the former (activated-calmodulin) was inhibited by cyproheptadine (Cyp) with IC50 75 mumol.L-1 (95% confidence interval was 18-319 mumol.L-1, r = 0.9118), while the Ca(2+)-ATPase activity of the latter (inactivated) was hardly influenced by Cyp. The results suggest that cyproheptadine antagonizes CaM, and its actions of the calcium antagonism and the anti-myocardial injury may, at least partially, be related to its CaM antagonism. PMID- 8010077 TI - [Influence of 11 ginsenoside monomers on action potentials of myocardiocytes]. AB - Eleven ginsenoside monomers were added to cultured myocardiocytes of neonatal Wistar rats in a concentration of 20 micrograms.ml-1. And the action potentials (AP) were led with microelectrodes. Rb1, Rb2, Rb3, Rc, Rg1, Rg2, Re, and Rh1 inhibited AP, decreasing APA by 20%, 13%, 5%, 18%, 30%, 37%, 28%, and 23%, respectively. The potency of the most effective monomer Rg2 20 micrograms.ml-1 was similar to that of the calcium channel blocker nimodipine 1.25 micrograms.ml 1. Rd, Rf, and Ro had no significant influence on AP. The average potency of the panaxatriol saponin (PTS) monomers were greater than that of the panaxadiol saponin (PDS) monomers. The above demonstrate the reason why the calcium channel blockade action of PTS is stronger than that of PDS results from the summation of monomer drug effects. PMID- 8010078 TI - Sympatho-inhibitory effects of r-l-glutamyl-l-dopa in conscious rabbits. AB - Renal and total norepinephrine (NE) spillover rates were studied with [3H] NE kinetic method during graded r-l-glutamyl-l-dopa (gludopa) i.v. infusion in conscious rabbits. Mean arterial pressure (MAP) and heart rate (HR) remained constant during the experiment. Gludopa i.v. infusion at 25 and 100 micrograms.kg 1.min-1 produced marked increases in urinary dopamine (DA) excretion and renal DA content. Although renal venous DA rose after gludopa infusion, the arterial DA was not significantly altered. Arterial plasma gludopa and levodopa levels reached 0.9 +/- 0.5, 3.2 +/- 0.8 micrograms.ml-1 and 3.0 +/- 1.8, 10.1 +/- 5.1 ng.ml-1 at the lower and higher gludopa doses, respectively. Gludopa elicited a pronounced dose-related fall in renal NE spillover, which only accounted for about one half of the reduction in overall NE spillover rate. Renal NE content was doubled. These results indicated that gludopa decreased the renal and extrarenal NE spillover to plasma. This reduction may be mediated by intrarenally synthesized DA via presynaptic DA-2 and alpha-2 receptors, but could also be explained by some central sympatho-inhibitory mechanism. PMID- 8010080 TI - Frequency- and voltage-dependent inhibition of delayed outward potassium current by flecainide in isolated atrial cell of guinea pig heart. AB - Effects of flecainide (Fle) on membrane currents were studied using an isolated single atrial cell from guinea pig hearts. The tight-seal cell clamp technique was used. In the current clamp condition, Fle prolonged significantly the atrial action potential (APD) with frequency dependence. Delayed outward K+ current and outward tail current were specifically inhibited by Fle in a frequency- and concentration-dependent fashion. Fle inhibited Ik more strongly as the membrane potential became more positive from +10 mV to +60 mV. The value of Ik was attenuated to 973 pA from 1105 pA of control and the value of tail current was reduced to 113 pA from 288 pA of control at 60 mV. The drug did not affect the holding current. The effects of Fle on the action potential and transmembrane ionic currents strongly suggested that the main mechanism of action of this agent was to inhibit the voltage-dependent potassium current. In the voltage clamp condition, Fle affected neither the conventional L type Ca2+ current nor the Ik1 current significantly. Our research proved that Fle was not completely consistent with the class Ic agents, because Fle could markedly increase the APD in the experiment. PMID- 8010079 TI - Presence of endothelium masks direct vasodilator effects of pyrogallol and methylthioninium chloride in perfused rat mesenteric artery. AB - In the perfused rat mesenteric artery vasoconstrictor responses to transmural nerve stimulation (TNS) were enhanced by pyrogallol (Pyr) 0.1 mmol.L-1 or methylthioninium chloride (Met) 0.01 mmol.L-1. But the duration of the effect of Pyr was brief, while the effect of Met remained stable. Met, but not Pyr, slightly increased the basal level of perfusion pressure. Contractile responses to the alpha adrenergic agonist methoxamine were also potentiated by both Pyr and Met, and in both cases their effects persisted as long as Pyr or Met was present. Superoxide dismutase (SOD) abolished or inhibited the potentiation produced by Pyr or Met. Both Pyr and Met inhibited the vasodilation produced by acetylcholine (ACh). However, after blockade of endothelial function both Pyr and Met inhibited vasoconstrictor responses to TNS in the presence of N omega-nitro-L-arginine methyl ester (L-NAME) 0.1 mmol.L-1, an inhibitor of nitric oxide synthesis, or removal of endothelium. After removal of endothelium both Pyr and Met produced vasodilator responses in a concentration-dependent manner. These results suggest that the ability of both Pyr and Met to potentiate contractile responses and inhibit vasodilator responses to ACh is due to generation of superoxide anion, and that the actions of Met may also involve direct inactivation of guanylate cyclase. The present study also suggests that both Pyr and Met have direct relaxing effects on vascular smooth muscle, effects which are masked by enhancing actions in the presence of endothelium. PMID- 8010081 TI - Synthesis of a new hydroxyethylene dipeptide isostere Phe psi [CH2CH (OH)]Phe as HIV-1 protease inhibitor. AB - A new type of pseudopeptide isostere exampled by Phe psi[CH2CH(OH)]Phe was synthesized from phenylalanine. The HIV protease inhibitory activity (IC50) of Noa-His-Phe psi[CH2CH(OH)]Phe-Ile-Amp was 0.8 pmol.L-1. PMID- 8010082 TI - Effects of U-50 488H, a kappa-agonist, on action potentials of isolated ventricular papillary muscle of guinea pigs. AB - Trans(+-)-3,4-dichloro-N-methyl-N-[2-(1-pyrrolidinyl) cyclohexyl] benzeneacetamide-methanesulfonate-hydrate (U-50 488H), a specific kappa-agonist, at 1-10 mumol.L-1 caused concentration-dependent reductions in the action potential duration at 50% and 90% of repolarization (APD50 and APD90) without modifying the resting potential (RP), the action potential amplitude (APA) and the maximal upstroke velocity (Vmax). The effects were attenuated by (-) (1R,5R,9R)-5,9-diethyl-2-(3-furylmethyl)-2L-hydroxy-6,7-benzomorphan (M(r) 2266 BS, 1 mumol.L-1), a specific kappa-antagonist which itself had no effect on the action potentials of the ventricular papillary muscle of guinea pigs, indicating that U-50 488H at 1-10 mumol.L-1 acts via specific cardiac kappa-receptors. At 100 mumol.L-1, U-50 488H not only shortened APD50 and APD90, but also reduced RP, APA, and Vmax, which were not attenuated by Mr 2266 BS (1 mumol.L-1) suggesting that the effects of U-50 488H at 100 mumol.L-1 were probably nonspecific. PMID- 8010083 TI - Application of NONMEM method for evaluation of relative biological availability of ofloxacin. AB - The nonlinear mixed effect model (NONMEM) method for analysis of population pharmacokinetics, was applied to evaluate the relative biological availability of 2 ofloxacin (Ofl) products. The data of randomized crossover study of 2 kinds of Ofl tablets in 12 healthy volunteers were analyzed by NONMEM, as well as standard approach. The relative biological availability evaluated by NONMEM (F = 97.3 +/- 5.0%) was close to that by standard approach (F = 98.2 +/- 3.6%). NONMEM was also valid in accurately evaluating the relative biological availability using sparse clinical data (F = 91.7 +/- 8.0%) which could not be analyzed by standard approach. Thus, the usefulness and advantages of NONMEM were ascertained for the evaluation of biological availability using observational or experimental data. PMID- 8010084 TI - Topical capsaicin treatment suppresses formalin-induced fos expression in rat spinal cord. AB - Capsaicin (Cap) is a pharmacological tool to inactivate nociceptive afferents. The present study was undertaken to investigate the effects of topical application of Cap to sciatic nerve on the formalin-induced expression of proto oncogene proteins c-fos in the rat spinal cord using immunohistochemical display of fos-like protein. In rats subjected to formalin injection into the hind paw, numerous fos-like immunoreactivity (FLI) neurons were found in the spinal dorsal horn, with heavy labeling in laminae I-II and V-VI. Following pretreatment of Cap, formalin-induced FLI expression was significantly abolished. It was suggested that activation of Cap-sensitive unmyelinated nociceptive afferents following formalin injection was primarily responsible for the activation of c fos gene. Our data also provided further evidence supporting that topical application was an effective way to block the transmission of noxious primary afferents. PMID- 8010085 TI - Antitumor effect of alpha isomer of anordrin in vitro and cell cycle arrest at G1 phase. AB - Alpha isomer of anordrin (2 alpha, 17 alpha-diethyl-A-norandrostane-2 beta, 17 beta-diol dipropionate, alpha-Ano) inhibited mouse hepatoma (Hep A) and P388 cell growth in vitro. alpha-Ano (20 micrograms.ml-1) inhibited the incorporation of [3H]uridine and [3H]thymidine into RNA and DNA within 3 h, but the inhibition of L-[3H]lysine incorporating into protein was not obvious. alpha-Ano had no effect on the DNA-dependent RNA synthesis with purified nuclei of Hep A cells. It is suggested that the inhibition of RNA and DNA syntheses is the major cause of the cytostatic effect. alpha-Ano blocked the P388 cells at G1/G0 phase, and the delay in G1/G0 to S phase transition plays an important role in the inhibition of P388 cell growth. PMID- 8010086 TI - Pharmacokinetics and tissue distribution of human recombinant interleukin-2 in mice. AB - 125I-labeled human recombinant interleukin-2 (125I-rIL-2) was prepared by iodogen method with rIL-2 and Na125I. Product was purified by Sephacryl S-200 gel filtration. Eluate fractions were identified by SDS-PAGE and compared with standard rIL-2. Radioactive 95% purified 125I-rIL-2 fractions were selected for pharmacokinetic study, with a specific activity of 56 PBq.mol-1. Concentration time curves after iv 75, 530, 603, and 6767 ng of 125I-rIL-2/mouse were fitted to a 3-compartment model: with a fast distribution phase T1/2 of 2 min, a slow distribution phase T1/2 of 30-120 min, and a terminal elimination T1/2 of 6-15 h. AUC was linearly related to the dosage (r = 0.9998). Systematic clearances were independent of the dosages. SDS-PAGE of plasma and urine samples showed that radioactivities due to 125I-rIL-2 were 81 +/- 13% (n = 16) and 91 +/- 8% (n = 3, at 4 h), respectively. Levels of 125I-rIL-2 after im were lower than those after i.v., with bioavailability of 0.57. Time to peak concentration was about 1.1 h. The highest levels were seen at 15 min after i.v. in liver, bile and kidneys, the concentration gradients were blood > adrenals > plasma > lungs > thyroid > spleen > jejunum > mesenteric lymph nodes > jejunum contents > ovaries > heart > bladder > thymus > feces in colon > thigh skeletal muscle > testes > brain > fat. Peak concentration time in most tissues were found at 15 min, but at 4 h in the feces.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8010087 TI - Synergistic effect of probimane on anticancer cytotoxicity of doxorubicin in vitro. AB - Using 3-(4,5-dimethythiazole)-2,5-diphenyltetrazolium bromide (MTT) method, the effect of probimane (Pro) on doxorubicin (Dox) cytotoxicity was studied. Pro 0.313, 0.625, and 1.25 micrograms.ml-1 potentiated cytotoxicity of Dox in Ehrlich ascites carcinoma (EAC) cells. Incubation of EAC cells with Dox 10 micrograms.ml 1 and Pro 116.5, 233, and 466 micrograms.ml-1 resulted in an increase in intracellular drug accumulation from 0.69 +/- 0.06 to 1.08 +/- 0.10 micrograms/10(7) cells. In S37-bearing mice, Pro 23.3, 46.6, and 116.5 micrograms.ml-1 enhanced the malondialdehyde (MDA) formation in tumor and liver mitochondria and decreased MDA formation in liver mitochondria. These results suggested that the increases of Dox accumulation and MDA formation in tumor cells by Pro might be the reasons for synergistic effect of Pro on Dox cytotoxicity. PMID- 8010088 TI - Presynaptic histamine H1- and H3-receptors modulate sympathetic neurotransmission in isolated guinea pig vas deferens. AB - The action of (R)-alpha-methylhistamine (alpha-MeHA), a selective H3-receptor agonist, on field stimulation induced contraction of guinea pig vas deferens was composed of 2 components: the "inhibition" (0.1-100 nmon.L-1) and the "enhancement" (1-10 mumol.L-1). In the presence of histamine H1 antagonist, chlorpheniramine (1 mumol.L-1), alpha-MeHA (0.1 nmol.L-1-10 mumol.L-1) showed only a concentration-dependent inhibition. Selective histamine H3-receptor antagonist, thioperamide (1 nmol.L-1-10 mumol.L-1) antagonized the inhibitory effect of alpha-MeHA and increased the contractile amplitude of vas deferens elicited by field pulses when thioperamide was used alone. alpha-MeHA 10 mumol.L 1 enhanced the contractile amplitude, which was reversed by chlorpheniramine 1 mumol.L-1, but not by ranitidine (1 mumol.L-1). Pyridelethylamine, an H1-receptor agonist, facilitated concentration-dependently the contractile response of vas deferens. The effect was antagonized by chlorpheniramine, but not by ranitidine. Dimaprit, an H2-receptor agonist had no effect on the field stimulation induced sympathetic response. Both alpha-MeHA and pyridelethylamine failed to influence the contraction of vas deferens elicited by direct field stimulation in smooth muscle or by exogenously applied norepinephrine. It was concluded that histamine H1- and H3-receptors existed in sympathetic terminals of guinea pig vas deferens and facilitated or inhibited the sympathetic neurotransmission. PMID- 8010089 TI - Inhibitory effects of triazolodiazepine on mouse splenocytes and peritoneal macrophages in vitro. AB - Effects of triazolodiazepine (Tri) on mouse splenocyte proliferation and macrophage phagocytosis were studied. Tri 0.1-10 mumol.L-1 significantly inhibited concanavalin A (Con A) 5 micrograms.ml-1 and lipopolysaccharides (LPS) 10 micrograms.ml-1-induced splenocyte proliferation and phagocytic activity of activated peritoneal macrophages. Tri 10 mumol.L-1 reduced Con A-induced colony stimulating factor release from mouse splenocytes and LPS-challenged intracellular and extracellular interleukin-1 production from peritoneal macrophages. These results partially explain the wide and strong anti inflammatory effects of Tri. PMID- 8010090 TI - Effects of mebendazole, albendazole, and praziquantel on fumarate hydratase, pyruvate kinase, and phosphoenolpyruvate carboxykinase of Echinococcus granulosus cyst wall harbored in mice. AB - Echinococcus granulosus cyst wall exhibited activities of fumarate hydratase (FH), pyruvate kinase (PK), and phosphoenolpyruvate carboxykinase (PEPCK) with 911-1433, 151-215, and 54-98U, respectively. The ratio of PK/PEPCK was 2.2-2.7, indicating that glycolysis is the main pathway of carbohydrate metabolism in the cyst wall. When infected mice were treated ig with mebendazole, albendazole or praziquantel at the respective daily dose of 25-50, 300, and 500 mg.kg-1 for 7-14 d, no apparent change of FH activity in the cyst wall was found, while PK and PEPCK activities in the cyst wall were markedly inhibited by mebendazole and albendazole. The inhibition rates of PK and PEPCK activities in mebendazole group were 85-88% and 90-92%, respectively, while in albendazole group were 55.3 and 71.6%, respectively. The results suggest that PK or PEPCK in the cyst wall may the important site attacked by effective anti-hydatid drugs. PMID- 8010091 TI - [C-fos expression in rat brain during seizure and electroacupuncture]. AB - C-fos proteins were visualized immunohistochemically in the brain of rats after seizures induced by injecting penicillin into hippocampus and by penicillin+electroacupuncture treatment. Three hours following seizures there was an evident expression of c-fos proteins in the hippocampus (CA1 area), dentate gyrus, piriform cortex, dorsal part of entorhinal cortex, and amygdaloid nucleus, and there was a dramatic increase of c-fos proteins in CA3 area and the areas mentioned above except the CA1 area where c-fos proteins apparently decreased after electroacupuncture treatment. The results showed that seizures can induce c fos proteins in some nuclei related with seizure and that electroacupuncture can also regulates the c-fos expression after seizure. PMID- 8010092 TI - [Effect of intracerebroventricular injection of norepinephrine and serotonin on somatosensory evoked potentials in rabbits]. AB - The components of somatosensory evoked potentials (SEP), P7, N9, P12, and N15, were recorded from dura mater before and after intracerebroventricular injection (icv) of monoamines. The peak latencies of P12 and N15 were prolonged and the amplitudes of P12 and N15 were decreased following icv norepinephrine (NE) 1 microgram.microliter-1 and serotonin (5-HT) 1 microgram.microliter-1. Generally, P12 and N15 restored to normal 1-2 h after icv NE and 5-HT. Dopamine (DA) 1 microgram.microliter-1, however, did not show any significant effect on SEP. Tolazoline (Tol) 2.5 micrograms.microliters-1 markedly potentiated the inhibitory effect of NE, but propranolol (Pro) 1 microgram.microliter-1 weakened the effect of NE on SEP. These results indicated that icv NE and 5-HT exerted an inhibitory effect on the somatosensory afferent function from thalamus to cortex and/or intercortical areas and alpha-adrenoceptor had an influence on the inhibitory effect of NE. PMID- 8010093 TI - [Whole-body autoradiographic localization of catecholamic acid in mice]. AB - Catecholamic acid [catechol-3,6-bis-(methyleneimino diacetic acid)] is a chelating agent synthesized in our institute. Whole-body autoradiographic study was carried out to determine the distribution of [14C]catecholamic acid in 5 adult male mice. Each mouse was injected i.v. 370 kBq. After various times the mice, under ether anesthesia, were immersed in a mixture of dry ice and hexane. Whole-body sections were made at -20 C, 20 microns in thickness. Results showed: (1) At 5 min, higher radioactivities appeared in blood, kidneys, gastrointestinal mucosa, bone, skin, and hair; moderate concentrations in liver, lungs, spleen, and salivary glands. (2) During 20 min and 3 h, the radioactivities decreased (gradually) in all tissues except the bone. (3) Intense radioactivity persisted in the bone, while only traces remained in the kidneys and intestinal mucosa throughout the 24 h period of observation. PMID- 8010095 TI - [Pharmacokinetics of harringtonine liposomes in rabbits]. AB - After i.v. free harringtonine (FH) and harringtonine liposomes (HL) with high and low encapsulation percentage (En%) to rabbits, their blood concentrations were determined by reverse-phase HPLC. The blood concentration-time curves were shown to fit a two-compartments open model. FH: T1/2 alpha = 1.32 +/- 0.24, T1/2 beta = 32 +/- 6 min; Low En % HL: T1/2 alpha = 4.12 +/- 0.25, T1/2 beta = 106 +/- 5 min; High En % HL: T1/2 alpha = 9.4 +/- 1.2, T1/2 beta = 209 +/- 5 min. PMID- 8010094 TI - [Sodium ferulate alleviated paracetamol-induced liver toxicity in mice]. AB - Sodium ferulate (SF) is one of the effective components of Angelica sinensis Diels. Pretreatment with SF (100 mg.kg-1 ig, qd x 10 d) inhibited the activity of serum alanine aminotransferase, prevented the depletion of liver glycogen and glutathione, increased the liver homogenate and microsomal glutathione S transferase activities, and reduced the malondialdehyde content, the membrane fluidity of liver microsome and the mitochondria in paracetamol (130 mg.kg-1, ip) induced liver toxicity in mice. These results demonstrated the hepato-protective action of SF in mice. PMID- 8010096 TI - [Effects of bimolane on cell cycle cytokinesis in human lymphocytes in vitro]. AB - Bimolane, 1,2-bis(4-morpholinomethyl-3,5-dioxopiperazinyl) ethane, is a new antineoplastic agent synthesized first in China. The effects of bimolane on the rate of S phase cells, mitotic index, and cytokinesis in human peripheral blood lymphocytes cultured in vitro were studied by autoradiography with [3H]TdR and counting the number of mono- and multi-nucleated lymphocytes. Results showed that bimolane (5, 10, 20 micrograms.ml-1) inhibited the progression of cell cycle, so that the rate of S and M phases decreased. Bimolane inhibited cytokinesis, which formed bi- and multi-nucleated cells. The effects were concentration-dependent. Bimolane induced micronuclei in mono- and bi-nucleated lymphocytes. Our results indicate that bimolane is a cytotoxic and genotoxic agent. PMID- 8010097 TI - [Distribution of 131I-cytotoxin 14 from Naja naja atra venom in rats]. AB - Cytotoxin 14 (CT14) from Naja naja atra venom was labelled with 131I by chloramine-T method and its tissue distribution was studied in rats. The highest concentration of the cytotoxin was found in kidney, 5979 dpm per mg weight, 14 times more than that of the control animals, at 0.5 h after i.v. injection and high concentrations were found in liver, spleen, pancreas, and adrenal. CT14 was also found in brain at 2 h after injection, 50 dpm per mg weight, 3 times more than that of the control. PMID- 8010099 TI - Effects of tubeimoside-1 on HIV core protein p24 and cytopathogenesis in vitro. AB - Tubeimoside-1 (Tub) is a triterpenoid saponin first isolated in China from Bolbostemma paniculatum (Maxim) Franquet, Cucurbitaceae. To find out whether Tub has any anti-infective activity on human immunodeficiency virus (HIV), we tested its effects on HIV core protein p24 (with an ELISA) and HIV-mediated cytopathogenesis (using a colorimetric assay). The results showed that Tub inhibited both p24 production and cytopathogenesis mediated by HTLV-IIIB, and the median effective concentrations (EC50) were 24.1 and 22.9 micrograms.ml-1, respectively. Tub also effectively neutralized the infection of 2 other isolates, HTLV-IIIRF and HTLV-IIIMN. It is concluded that Tub had an inhibitory action on the infection of HIV-1 isolates and would be a promising candidate for treatment of AIDS. PMID- 8010098 TI - [Effects of dl-tetrahydropalmatine on blood pressure and norepinephrine and epinephrine contents in peripheral tissues]. AB - Administration of dl-tetrahydropalmatine (THP) i.v., ip, and ig lowered the pressure and concurrently slowed the heart rate in anesthetized rats. The hypotensive and bradycardic effects were not produced by injecting THP into the vertebral artery in anesthetized rabbits. These results suggest that the site of hypotensive action of THP may not be a central one. The HPLC coupled with electrochemical detection showed that the contents of norepinephrine (NE) in the heart, aorta, and femoral artery and epinephrine (E) in the adrenal gland were markedly reduced by THP (P < 0.01). A positive correlation was found between the hypotensive effect and the reduction of NE in the aorta and femoral artery (r = 0.97, P < 0.01). PMID- 8010100 TI - Effect of cholinesterase inhibition in vitro by huperzine analogs. AB - Huperzine (Hup) A and B were first discovered and studied by Chinese. Fourteen analogs of Hup were tested for their anticholinesterase (anti-ChE) activity by colorimetric method using rat erythrocyte membrane and serum as enzyme sources. Hup-A showed the highest anti-AChE potency. The anti-BuChE activity of (-)dihydro and (-)tetrahydro analogs were potent than those of Hup-A. Their anti-AChE activities were comparable to those of physostigmine and galanthamine. Dihydro analog inhibition was of the mixed competitive type with a Ki value of 0.12 mumol.L-1. Tetrahydro analog inhibition was of the competitive type with a Ki value of 0.56 mumol.L-1. They were different from isoflurophate to bond to AChE in a reversible manner. PMID- 8010101 TI - Effects of kappa, sigma, and phencyclidine receptors agonists in rat tail arteries of spontaneously hypertensive rats. AB - The effects of the kappa receptor agonist trans-4-dichloro-N-methyl-N-(2-(1 pyrrolidin)cyclohexyl)-benzen eacefamide methane sulfonate (U-50 488H), etorphine, the sigma (sigma) receptor agonists (+)-3-(3-hydroxychenyl)-N-(1 propyl) piperidine ((+)-3-PPP), 1, 3-di-o-tolyl-guanidine (DTG), and the phencyclidine (Phe) receptor agonists Phe, N-(1-(2-thienyl)cyclohexyl) piperidine (TCP), and dizocilipine maleate (MK-801) on electrically stimulated constriction (ESC) were investigated in the rat tail arteries (RTA) of spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto (WKY) rats. Etorphine and U 50 488H inhibited the response to ESC in SHR more than that in WKY. The effects of U-50 488H were greater than those of etorphine. The IC50 and Kact of U-50 488H in SHR were 2.5 +/- 2.0 and 0.43 +/- 0.22 mumol.L-1, respectively, while the corresponding figures in WKY were 23 +/- 15 and 2.3 +/- 1.0 mumol.L-1, respectively (P < 0.05). The inhibitory effects of (+)-3-PPP on ESC in RTA of SHR were weaker than those in WKY. Its IC50 and Kact in SHR were 11.6 +/- 5.4 and 0.87 +/- 0.30 mumol.L-1, respectively, while the corresponding figures in WKY were 0.63 +/- 0.16 and 0.35 +/- 0.18 mumol.L-1, respectively (P < 0.05). But the inhibitory effect of DTG was very slight and the difference of Kact between WKY and SHR was not significant. The enhancing effects of Phe, TCP, and MK-801 in SHR were not at all different from those in WKY at each concentration tested.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8010102 TI - Blocking effect of rhynchophylline on calcium channels in isolated rat ventricular myocytes. AB - The effect of rhynchophylline (Rhy) on L-type Ca2+ channel current was studied in rat ventricular myocytes using patch-clamp whole-cell recording technique. When the holding potential was -40 mV, cells were depolarized to 0 mV for 250 ms at frequency of 0.5 Hz, Rhy 10 and 50 mumol.L-1 reduced verapamil-sensitive Ca2+ inward current by 60% and 80%, respectively, without affecting the voltage dependency of the maximal activation of Ca2+ current. This indicated that the effect of Rhy on the activation of Ca2+ channel was voltage-independent. The effect of Rhy on Ca2+ current reached the maximum at 10 min and was partially recovered by washout of Rhy. A pD2 value of 5.91 and Hill coefficient of 1.1 were obtained from the concentration-response curve. PMID- 8010103 TI - Protection of l-arginine against oxygen free radicals-injured rabbit aortic endothelium. AB - This study was to investigate the protective effect of l-arginine, a precursor of endothelium-derived relaxing factor (EDRF), against damages due to endogenous or exogenous oxygen free radicals (OFR) on the aortic endothelium. The superfusion cascade bioassay of rabbit thoracic aorta was used. Endogenous OFR were generated by diethyldithiocarbamate (DETC) to deplete the cytosolic Zn-Cu form of superoxide dismutase (SOD). Exogenous OFR were generated by electrolysis of Krebs' solution. Acetylcholine (ACh) was infused through the donor aortic segment and relaxation of detector aortic ring was used as an indicator of the release of EDRF. The content of malondialdehyde (MDA) in the donor aorta was assayed biochemically. Both DETC and electrolysis inhibited vasodilator responses to ACh and increased MDA content in the aortic segment. Inhibition of DETC was abolished by exogenous SOD. l-Arginine improved impairment of endothelium-dependent relaxation and reduced elevation of MDA content by DETC or electrolysis. These results suggest that l-arginine presents a protective effect of endothelium against damage due to endogenous or exogenous OFR, and that the protective effect of l-arginine may be correlated with reduction in lipid peroxidation. PMID- 8010104 TI - Sympatholytic effect of captopril in regression of cardiovascular remodeling in spontaneously hypertensive rats. AB - Fifty-eight spontaneously hypertensive rats (SHR) at 12 wk of age were divided into 3 groups: A) captopril (Cap) 20 mg.kg-1.d-1; B) clonidine (Clo) 30 micrograms.kg-1.d-1; C) Clo 30 micrograms.kg-1.d-1 + Cap 20 mg.kg-1.d-1 orally for 24 wk. Concomitant administration of Cap and Clo did not result in more lowering of the systolic blood pressure (SBP) than that by Cap alone. Regression of left ventricular hypertrophy (LVH) were remarkable in Groups A and C, but not to the extent in that of WKY. No significant difference between these two groups was found. Cap alone resulted in a greater decrease of myocardial norepinephrine (NE) than that of Groups B and C. The wall/lumen ratio and the number of smooth muscle cell (SMC) layers of renal artery decreased in Groups A and C, but little difference was found between them. It seemed that combined blockade of renin angiotensin-aldosterone (RAA) system and sympathetic nervous system (SNS) did not produce more significant BP reduction and reversal of cardiovascular remodeling than Cap alone did. The sympathetic inhibitory effect of angiotensin converting enzyme inhibitor (ACEI) was not enhanced by sympatholytic treatment. PMID- 8010105 TI - Effects of endothelin-1 on isolated uterine horns in estrogen-primed and pregnant mice. AB - Mouse uterine horns from 4 states (estrogen-primed and early-, mid-, and late pregnancy) were used to study the effect of endothelin-1 (ET) vs carboprost (Car) and oxytocin (Oxy). In K(+)-Krebs (KCl 40 mmol.L-1) solution, ET (1-300 nmol.L 1), Car (0.002-20 mumol.L-1), and Oxy (0.6-60 nmol.L-1) evoked concentration dependent increases in tension of the uterine horns from 4 different states. Emax for ET were 1.12 +/- 0.26, 1.27 +/- 0.18, and 1.49 +/- 0.13 g in early-, mid-, and late-pregnancies, respectively. Emax for Car in mid- was twice that in late pregnancy, whereas Emax for Oxy in late- was thrice that in mid-pregnancy. EC50 for ET were 9.6, 5.8, and 6.3 nmol.L-1 in early-, mid-, and late-pregnancies, respectively, and were only 2% to 7% of that for Car and 3-15 times of that for Oxy in various gravid stages. The results suggest that the contractile activity of pregnant mouse uterus to ET is more potent than that of Car while slightly weaker than that of Oxy. PMID- 8010106 TI - Inhibitory effect of tetrahydroberberine on platelet aggregation and thrombosis. AB - Tetrahydroberberine (THB), an alkaloid extracted from Corydalis ambigua, inhibited the rabbit platelet aggregation triggered by arachidonic acid (AA), ADP, and collagen with IC50 of 0.86, 1.31, and 1.10 mmol.L-1, respectively. THB reduced the thromboxane B2 (TXB2) generation in rabbit platelet-rich plasma triggered by AA. THB 30 mg.kg-1.d-1 ip for 3 or 5 d restrained the ADP-induced platelet aggregation in rats. THB 30 mg.kg-1.d-1 ip for 1, 3, or 5 d inhibited the AA-induced platelet aggregation in rats. THB 15-30 mg.kg-1 iv showed an inhibition of venous thrombosis in rats. The results show that THB is a potent inhibitor of platelet aggregation in vitro and in vivo and is a promising antithrombotic drug. PMID- 8010107 TI - Cardiovascular responses to intracerebroventricular injection of GABA in renovascular hypertensive rats. AB - Effects of central GABAergic stimulation on cardiovascular function were evaluated in 2-kidney, 1-clip (2K1C) renovascular hypertensive rats (RVHR). Intracerebroventricular injection (icv) of GABA (100 and 200 micrograms) reduced blood pressure (BP) to a greater degree in RVHR as compared with sham-operated controls, and the greatest response was seen in RVHR 4 wk after operation (4 wk RVHR). In addition, a decreased sensitivity of baroreflex was observed in 4 wk RVHR, and was improved by icv GABA. Pretreatment with icv captopril (200 micrograms) only reduced BP moderately in 4 wk-RVHR, but attenuated remarkably the depressor effect of GABA. On the contrary, pretreatment with ip captopril was less effective in attenuating the depressor effect of GABA. Our results indicated that RVHR was deficient in central GABAergic inhibition on BP control, for GABAergic stimulation reduced BP to a greater degree and improves the decreased sensitivity of baroreflex in RVHR; the depressor effect of GABA is mediated, at least in part, by inhibiting brain angiotensin system. PMID- 8010108 TI - Effects of 3,4-diaminopyridine on myoplasmic calcium and phosphoinositide hydrolysis in frog sartorius muscle fibers. AB - Using Ca(2+)-selective microelectrodes, the effects of 3,4-diaminopyridine (DAP) on myoplasmic calcium ([Ca2+]i) were studied in frog satorius muscle fibers. DAP induced an increase of [Ca2+]i in a concentration-dependent manner. DAP 1 mmol.L 1 increased the [Ca2+]i from control 166 +/- 41 nmol.L-1 to 416 +/- 69 nmol.L-1 (n = 10). In the absence of external calcium, DAP still enhanced [Ca2+]i. [Ca2+]i of the fibers bathed in Ca(2+)-free Ringer's solution containing DAP 1 mmol.L-1 was 152 +/- 43 nmol.L-1, which was significantly higher than 77 +/- 35 nmol.L-1 of [Ca2+]i of the fibers in Ca(2+)-free Ringer's solution. In addition, DAP promoted the hydrolysis of phosphoinositides, and DAP-induced hydrolysis was more in the presence of external calcium. It is suggested that, through enhancing the hydrolysis of phosphoinositides, DAP released Ca2+ from intracellular Ca2+ store in frog sartorius muscle fibers. PMID- 8010109 TI - Mechanisms of relaxation by pyrogallol and methylthioninium chloride in perfused rat mesenteric artery. AB - In perfused rat mesenteric arteries without endothelium, pyrogallol (Pyr) or methylthioninium chloride (methylene blue, Met) produced a concentration dependent relaxation. Superoxide dismutase abolished inhibition by Pyr, but not Met, of vasoconstrictor responses to transmural nerve stimulation (TNS). Neither catalase nor deferoxamine had any effect on vasodilator responses to Pyr or Met. Vasodilator responses to Pyr were unaltered by N omega-nitro-L-arginine methyl ester (L-NAME), indomethacin, or capsaicin. Similarly, the relaxing effect of Met was unaffected by indomethacin or capsaicin. These findings suggest that vasodilator responses to Pyr may be due to endothelial-independent generation of superoxide anion. In contrast the relaxation produced by Met appears to be due to a direct action on vascular smooth muscle independent of superoxide anion generation. PMID- 8010110 TI - Effects of toosendanin on electric and mechanical properties of guinea pig papillary muscles. AB - Effects of toosendanin (TS) on the action potentials and contractile force in guinea pig papillary muscles were examined using a standard microelectrode technique. TS concentration-dependently increased the action potential duration at 90% repolarization (APD90) of the fast action potentials. In the presence of a Ikl channel blocker BaCl2, the effects of TS on lengthening the APD90 were completely abolished, thereby suggesting that TS inhibited the inward rectifier K+ current Ikl. The APD and contractile force of aminophylline-induced slow action potentials were potentiated by TS in a concentration-dependent manner. In the presence of BaCl2, both effects of TS were completely abolished. The effect of TS on enhancing contractile force was abolished by the addition of CdCl2, with the prolongation of APD preserved. Thus, TS selectively inhibited the inward rectifier K+ current Ikl with a positive inotropic effect, resulting from a delay in Ca channel inactivation which was secondary to delay in ventricular repolarization. PMID- 8010111 TI - [Memory-enhancing effects of argipressin and its relationship with periaqueductal gray]. AB - Wistar rats were trained to perform shuttle-box active avoidance response. In experiment A, 43 rats were implanted cannulae in bilateral periaqueductal gray (PAG) and argipressin (Arg) was injected. Arg 0.15 or 0.3 ng but not 0.05 ng retarded the extinction of avoidance response. In experiment B, 37 rats were set up bilateral electrolytic lesions of PAG or sham lesioned. Arg (6 micrograms.kg 1, ip) was injected after training. PAG lesions blocked the influence of ip Arg on memory enhancement. The results indicated that Arg may act directly on CNS to modulated memory and PAG may play an important role in this process. This observation provided further support to the previous suggestion that certain limbic midbrain structures were involved in memory-enhancement by Arg. PMID- 8010112 TI - [Facilitation of cholinergic transmission by huperzine A in toad paravertebral ganglia in vitro]. AB - Using the intracellular recording techniques of toad paravertebral ganglia (PVG), the effects of cholinesterase inhibitor huperzine A (Hup-A), an alkaloid first isolated from Huperzia serrata (Thunb) Trev in China, on the synaptic transmission were studied. In 30 PVG cells tested, no remarkable changes in membrane potential and input resistance were observed during superfusion of Hup-A 0.3 or 1 mumol.L-1 for 15 min. The rate of orthodromic action potential evoked by preganglionic stimulation was increased by Hup-A 0.3 or 1 mumol.L-1 (n = 12, P < 0.05), and much faster, stronger, and longer in action at 50 or 100 mumol.L-1 (n = 11). The amplitude and duration of exogenous acetylcholine-, but not carbachol , induced depolarization were increased (P < 0.05). It is concluded that Hup-A is a selective and potent cholinesterase inhibitor, by which action it facilitates the cholinergic transmission of PVG neurons. PMID- 8010113 TI - [Enhancing effects of Herpesvirus hominis on sodium glutamate neurotoxicity]. AB - The neurotoxic effects of sodium glutamate (MSG, 2.5 g.kg-1 sc) and the enhancing effects of neurotropic Herpesvirus hominis (HVH, 0.2 ml/mouse ip) on MSG toxicity were studied through histomorphological observations, together with detection of the concentration of both mitochondrial protein bound Ca2+ and intracellular free Ca2+ ([Ca2+]i) by the Tb3+ fluorescent probe and Ca2+ indicator Fura-2/AM, respectively. It was found that in 10-d-old mice the neurons in arcuate hypothalamic nucleus degenerated severely after treatment with HVH+MSG, showing swollen edematous cytoplasm, dark pyknotic nuclei as well as a decrease in the amount of the neurons. The hypothalamic and spinal cord mitochondrial Tb3+ relative fluorescent intensity increased from 20 +/- 3 and 20 +/- 1 to 28 +/- 5 and 34 +/- 6, ie, the mitochondrial protein bound Ca2+ reduced significantly. MSG elevated the [Ca2+]i levels from 0.11 +/- 0.03 to 0.69 +/- 0.19 mumol.L-1 by not only stimulating the Ca2+ influx but also releasing the Ca2+ from intracellular stores. These findings suggested that MSG neurotoxicity was probably related to the overloading of neuroplasmic Ca2+, the destruction of neuronal abilities to deplete or sequester the intracellular Ca2+, as well as the irreversible neuronal injury and death. PMID- 8010114 TI - [Effects of anisodine on respiratory center]. AB - Anisodine (Ani), a new selective M receptor blocking agent, was isolated from Scopolia tangutica in China. The structure of Ani is similar to scopolamine. Ani (2.5, 5 mg.kg-1 i.v., or 0.6 mg.kg-1 icv) increased the rate of phrenic nerve discharges (PND), while the time of inspiration and expiration, and the spikes in each PND were reduced in urethan-anesthetized rats. In urethan-anesthetized rabbits, Ani (2.5 mg.kg-1 i.v., or 0.2 mg.kg-1 applied onto obex) increased the rate of PND. In tubocurarine-pretreated and artificially ventilated rabbits, Ani (2.5 mg.kg-1 i.v., or 0.2 mg.kg-1 applied onto obex) increased the rate of inspiratory neurone firing in nucleus tractus solitarius. Oxotremorine (40 micrograms.kg-1 i.v.) antagonized the Ani effects. Ani (2.5 mg.kg-1 i.v.) partially antagonized the respiratory depression induced by morphine. These results provide the evidence that Ani stimulates the respiratory center through cholinergic M pathway and there may be some neuronal interaction between cholinergic and opiate receptors in the control of respiratory center. PMID- 8010115 TI - [Effects of Viscum coloratum flavonoids on fast response action potentials of hearts]. AB - The effects of the total flavonoids of Viscum coloratum (VCF) on the fast response action potentials (FAP) of canine Purkinje fibers and guinea pig ventricular papillary muscles were studied by glass-microelectrode technique. The effects of VCF on the ionic currents through cellular membrane were analysed with selective ion blockers (CsCl, verapamil, and TEA+), respectively. VCF (100 micrograms.ml-1) accelerated the repolarization of FAP and increased delta ERP/delta APD ratio, which were related to decreasing Isi and increasing Ix. It was suggested that the anti-tachyarrhythmic mechanism of VCF was attributed to prolonging ERP relatively and to abolishing reentrant excitation. PMID- 8010116 TI - [Sites of analgesic action of 3,15-diacetylbenzoylaconine]. AB - In the rat hot plate test, vocalization induced by electric stimulation, tail flick test, and the mouse acetic acid writhing test, 3, 15-diacetylbenzoylaconine (DABA) ip exhibited a dose-dependent analgesic activity. Intrathecally (ith) administered DABA (527, 1186 micrograms.kg-1) had no analgesic action. Microinjection of DABA 35-75 micrograms.kg-1 or 20 micrograms into the cerebral ventricle (icv) or the periaqueductal gray (PAG) exerted a remarkable analgesic activity, which was abolished after bilateral lesions of locus coeruleus (LC). Microinjection of DABA (20 micrograms) into LC failed to produce apparent analgesic action. These results suggested that the sites of analgesia of DABA were mainly at the central supraspinal structures, and PAG was one of the primary sites, while LC was one of the intermediate links. PMID- 8010117 TI - [Effects of puerarin on cat vascular smooth muscle in vitro]. AB - Puerarin is an isoflavone compound isolated from Pueraria lobata (Wild). This study characterized the vascular action of puerarin in order to more clearly elucidate its pharmacological activities. Helically cut strips of cat femoral veins and renal arteries were suspended in an organ chamber filled with Krebs bicarbonate solution for measurement of isometric force development. In the cases of femoral veins and renal arteries isoproterenol (0.01 mumol.L-1 -0.1 mmol.L-1) caused relaxation of methoxamine-induced contraction (0.01 mmol.L-1) in a concentration-related manner. Puerarin (0.01-0.1 mmol.L-1) inhibited the relaxation response to isoproterenol in a concentration-response fashion. Propranolol (0.1-1 mumol.L-1) inhibited the isoproterenol-induced relaxation too. Puerarin (0.1mmol.L-1) did not alter the relaxation response to nitroglycerin (1 mumol.L-1). These results indicated that puerarin acted as a beta-adrenoreceptor antagonist in isolated arteries and veins. PMID- 8010118 TI - [Enhancement on expression of LDL receptors in cultured rhesus renal epithelial cells by verapamil]. AB - In order to investigate the anti-atherogenic properties of calcium antagonists, human serum low density lipoproteins (LDL) were isolated by density gradient ultracentrifugation and iodinated with 125I by iodine monochloride method. Effects of verapamil on activity of LDL receptors in cultured rhesus renal epithelial cells were examined by radioligand analysis. The receptor-mediated binding, internalization, and degradation of cultured cells pretreated with verapamil 44 mmol.L-1 for 24 h and cells pretreated for 24 h and incubated for 10 h with verapamil were increased compared with control group (61 +/- 11, 52 +/- 8 vs 20 +/- 3.5, 1006 +/- 106, 579 +/- 124 vs 253 +/- 78, 630 +/- 43, 541 +/- 46 vs 374 +/- 53 125I-LDL/micrograms.g-1 cell protein). In verapamil-treated cells without verapamil pretreatment, increased internalization and degradation were not significant, and binding was not increased. When the cells were pretreated with verapamil 22 mmol.L-1 for 24 h and then incubated with 5, 20, 50 125I LDL/mg.L-1, binding and internalization were increased, increased degradation was seen only with 50 125I-LDL/mg.L-1. The results indicated that the verapamil enhances expression of LDL receptor in cultured rhesus renal epithelial cells, which might contribute to the protective effects of calcium antagonists in experimental and human atherosclerosis. PMID- 8010119 TI - [Inhibition of mexiletine on sodium current in dorsal root ganglion neurons of rats]. AB - Using whole-cell configuration of patch clamp technique we found that mexiletine (Mex) reversibly inhibited the sodium current in a voltage- and use-dependent manner in cultured dorsal root ganglion (DRG) neurons. The threshold concentration of Mex was 5 mumol.L-1. The inhibitory action heightened with increasing concentrations of Mex. Complete inhibition was achieved at 150 mumol.L 1 and the 50% inhibition concentration was 31 mumol.L-1. It is suggested that the inhibition of Mex on sodium current in neurons may be one of the mechanisms of its anti-ischemic and anti-anoxic effects on the neuron. PMID- 8010120 TI - Induction of delayed afterdepolarizations and triggered arrhythmias in isolated Purkinje fibers: comparison of resibufogenin and acetylstrophanthidin. AB - The purpose of this study was to compare the electrotoxicological effects of resibufogenin (RBG) (n = 14) with acetylstrophanthidin (AS) (n = 14) to induce delayed afterdepolarization (DAD) and triggered activity (TA), and their alteration of the electrophysiological properties in sheep cardiac Purkinje fibers using the extracellular electrograms, signal averaging, and standard microelectrode techniques simultaneously. The results indicated: 1) Lower toxic dose of RBG (0.52 mumol.L-1) and AS (0.25 mumol.L-1) induced intracellular and extracellular DAD (DAD-I and DAD-E) at pacing cycle length of 990 and 690 ms. 2) Higher toxic dose of RBG (2.6 mumol.L-1) and AS (5.0 mumol.L-1) induced DAD and TA, nonsustained or sustained premature action potential and oscillatory potentials; 3) At the beginning period of superfusing the drugs, both RBG and AS caused changes of the electrophysiological characteristics. This study demonstrates that the electro-toxicological characteristics and electrophysiological properties of RBG are similar to that of AS and suggests that RBG belongs to the family of digitalis-like drugs. PMID- 8010121 TI - The racing camel (Camelus dromedarius). Physiology, metabolic functions and adaptations. General materials and methods. PMID- 8010122 TI - Haematology in the racing camel at rest: seasonal and training variations. PMID- 8010123 TI - Skeletal muscle morphology and metabolic potential. PMID- 8010124 TI - Some physiological responses to incremental treadmill exercise in the racing camel. PMID- 8010125 TI - Oxygen uptake in the racing camel at rest and during treadmill exercise. PMID- 8010126 TI - Metabolic responses to prolonged exercise in the racing camel. PMID- 8010127 TI - Metabolic responses to maximal intensity exercise in the racing camel. PMID- 8010128 TI - Adaptations to training in the racing camel. PMID- 8010129 TI - Some comparative aspects on the camel as a racing animal. PMID- 8010130 TI - The racing camel (Camelus dromedarius). Physiology, metabolic functions and adaptations. Background and general introduction. PMID- 8010131 TI - Quantification of tissue damage in the feline small intestine during ischaemia reperfusion: the importance of free radicals. AB - Intestinal ischaemia is accompanied by characteristic mucosal lesions, which can be graded according to a six-grade system proposed by Chiu et al. (1970). This report describes a continuous grading system which makes it possible to quantify the intestinal damage in connection with ischaemia-reperfusion. The present morphometric method is based on quantitative histological analysis of intestinal biopsies performed on 200 histological sections from 44 cat experiments. Radical formation was quantified by infusing close i.a. a spin trap, OXANOH, which produces a secondary stable radical, OXANO., after reacting with radicals in the tissue. OXANO. concentration was determined in venous blood samples with electron spin resonance. We demonstrate a highly significant correlation between the grading system of Chiu et al. (1970) and the morphometric analysis of this study. The tissue damage was located exclusively in the intestinal villi. Comparing the mucosal damage that occurs during 60 min of intestinal ischaemia (superior mesenteric artery pressure 15-25 mmHg) with that seen during the first 30 min reperfusion this study shows that the villus damage occurring during ischaemia is at least twice as large as the aggravation seen upon reperfusion. Furthermore, the authors demonstrate a significant correlation between rate of radical formation and villus tissue damage particularly during the first 30 min after ischaemia. It is concluded that the proposed quantitative morphological method represents a non-discrete grading system for evaluating tissue damage in connection with ischaemia-reperfusion in the small intestine. The ischaemia itself inflicted a more severe damage to the intestine than reperfusion. A significant correlation between damage and radical formation was demonstrated during the reperfusion. However, the results suggest that factors other than radical formation are of importance in explaining the tissue damage upon reperfusion. The nature of these factors is presently unknown. PMID- 8010132 TI - Effects of intensified endurance training on the concentration of Na,K-ATPase and Ca-ATPase in human skeletal muscle. AB - Thirty-nine moderately endurance trained males increased their normal training programme of 2.2 h week-1 with an average training intensity of 65% of maximum heart rate (HRmax) to 2.7 h week-1 and a mean intensity of 78% of HRmax. Performance tests and measurements of the total concentrations of Na,K-ATPase (3H ouabain binding) and Ca-ATPase, fibre type distribution and fibre area were performed in biopsies from the vastus lateralis muscle before and after increased training. The 6 weeks of training elevated VO2max from 54.9 +/- 3.1 to 58.3 +/- 3.0 ml O2 min-1 kg-1 (P < 0.0001). Exercise time to exhaustion at 86% of VO2max (pre-training) increased from 35 +/- 8 to 61 +/- 17 min (P < 0.0001). The concentration of Ca-ATPase was unaffected by the intensified training (6.74 +/- 1.03 vs. 6.68 +/- 1.07 nmol g wet wt-1), but the concentration of Na,K-ATPase increased from 307 +/- 43 to 354 +/- 59 pmol g wet wt-1 (P < 0.0001). The relative distribution of FT-fibres was correlated with the concentration of Ca ATPase (r = 0.72, P < 0.0001). The data support the view that intensive training induces an upregulation of the concentration of skeletal muscle Na,K-ATPase, but no change in the total capacity for reaccumulation of Ca2+ into the SR. There was no correlation between the concentrations of Na,K-ATPase, Ca-ATPase and indices of endurance performance. PMID- 8010133 TI - Characteristics of renal sympathetic nerve activity in experimental congestive heart failure in the rat. AB - Recently emerging evidence has indicated that efferent renal sympathetic nerve activity (RSNA) is increased in congestive heart failure (CHF). In the present study the cyclic activity of the renal nerve in the normal and CHF rat was studied. An ischaemic myocardial lesion resulting in CHF was induced by left coronary artery ligation. Sham-operated rats subjected to thoracotomy served as normal controls. Renal sympathetic nerve activity was recorded under chloralose anaesthesia. The neural cycle activity was significantly higher in CHF (47 +/- 3%) compared with sham-operated rats (34 +/- 3%, P < 0.005). Baroreceptor control of RSNA was significantly attenuated in CHF compared with normal control rats (P < 0.005). In response to noxious thermal stimulation by 48 degrees C water immersion of the tail tip, the increase of RSNA was significantly higher in CHF compared with sham-operated rats. A stepwise 15% blood volume expansion over 5 min which induced no alterations of blood pressure or heart rate (HR) resulted in a gradual decrease of RSNA in control rats by approximately 25% at the end of the volume expansion procedure. In CHF rats however, there was no significant change in RSNA during volume expansion. It is concluded that in CHF rats: (1) efferent RSNA is increased; (2) baroreceptor control of RSNA is decreased; (3) RSNA in response to cutaneous thermal noxious stimulation is exaggerated; and (4) RSNA inhibition by cardiopulmonary receptors is blunted. PMID- 8010134 TI - Endothelium dependence of prostanoid-induced relaxation in human hand veins. AB - The endothelium dependence of prostanoid-induced relaxation was examined in human isolated hand veins precontracted by endothelin. Indomethacin (10(-6) mol l-1) and the thromboxane A2-receptor antagonist BM 13.505 (10(-6) mol l-1) were present throughout. The endothelium was removed by insufflating carbogen through the vessel lumen. Prostaglandin (PG) F2 alpha, PGE1, PGE2, and prostacyclin (PGI2) elicited concentration-dependent relaxant effects. Removal of the endothelium reduced the relaxation induced by PGF2 alpha and PGE2, but not that elicited by PGE1 and PGI2. The order of potency was PGE2 approximately PGE1 approximately PGI2 > PGF2 alpha regardless of the presence or absence of endothelium. The relaxation elicited by an acidified solution of NaNO2 (generating nitric oxide) was almost identical in intact and endothelium-denuded vein segments. The results are compatible with the existence of two prostanoid receptor populations mediating relaxation: (1) one located on the smooth muscle cells and; (2) another present on the endothelium or possibly on the smooth muscle and modulated by the endothelium. The latter receptor appears to be activated by PGF2 alpha and PGE2, but not by PGE1 and PGI2. PMID- 8010136 TI - Sex differences in endocrine response to hyperthermia in sauna. AB - Neuroendocrine response was investigated during and after a single 20 min bath in sauna (80 degrees C) in a group of 8 healthy men and 8 healthy women. In an additional group of 8 young men, the dynamics of plasma ACTH and cortisol levels were studied during a 30 min sauna exposure (90 degrees C). This dynamic study showed a biphasic response of plasma cortisol which decreased during the initial phase of sauna bath (15 min) and increased thereafter, reaching its maximum 15 min after the end of bathing. Maximal increase in plasma ACTH levels occurred 15 min earlier. In the first sauna exposed group the increase in body temperature was the same (about 2 degrees C) in both sexes. Nevertheless, the elevation in plasma ACTH concentration was significantly more pronounced in women than in men. In the plasma collected at the end of sauna bath inside the sauna room, a significant rise in both adrenaline and noradrenaline levels was found. Though the catecholamine responses were similar in both groups, the increase in heart rate during sauna bath was significantly higher in women. Sauna-induced prolactin release was also more pronounced in women compared with men. Thus hyperthermia induced by sauna exposure resulted in a more pronounced neuroendocrine activation in women compared with men. Moreover, it is evident that repeated blood sampling is necessary to reveal the sauna-induced activation of some hormonal systems. PMID- 8010135 TI - Ischaemic episodes of less than 5 minutes produce preconditioning but not stunning in the isolated rat heart. AB - The aim of the present study was to examine whether ischaemic episodes of less than 5 min could induce preconditioning or stunning in the isolated rat heart. Hearts were subjected to total global ischaemia of 1, 2 and 4 min followed by 10 min of reperfusion before an 18-min main ischaemic period and 30 min of reperfusion. The effects on physiology, purine metabolism and anaerobic glycolysis were compared with a control group subjected to the main ischaemia only. The brief ischaemic episodes did not produce stunning based on the recovery of left ventricular developed pressure (LVDP) and heart rate (HR) product during the first reperfusion. Preconditioning of 11-14% increased recovery of LVDP x HR during the second reperfusion was observed in the 1- and 4-min group. In the 2 min group a low repayment of flow debt during the first reperfusion was associated with a slightly reduced recovery of LVDP x HR compared to the other preconditioned groups during the second reperfusion. Only in the 4-min group was preconditioning associated with fewer breakdown products of the purine nucleotide pool (adenosine) and anaerobic glycolysis (lactate) in both tissue and effluate after the main ischaemia. Preconditioning (reflected in recovery of function) could be produced with ischaemic episodes of less than 5 min that did not produce stunning. Thus, stunning is probably not the primary cause of preconditioning. PMID- 8010138 TI - The transition between walking and running in humans: metabolic and mechanical aspects at different gradients. AB - Five subjects walked and ran at overlapping speeds and different gradients on a motorized treadmill. At each gradient the speed was obtained at which walking and running have the same metabolic cost (Sm) and the speed of spontaneous (Ss) transition between the two gaits was measured. Ss was found to be statistically lower than Sm at all gradients, the difference being in the range of 0.5-0.9 km h 1. The motion analysis of walking reveals that at all gradients and at increasing speed: (1) the percentage of recovery, an index of mechanical energy saving related to the pendulum-like characteristic of walking, decreases; (2) the lower limb spread reaches a limit in walking; and consequently (3) both the stride frequency and the internal mechanical work, due to limb acceleration in relation to the body centre of mass, increase much more in walking than in running. Switching to a run, although implying a higher frequency, makes the internal work decrease as a result of the lower limb spread. In this paper several influences, such as the 'ratings of perceived exertion' (RPE), on the choice of beginning to run when it is more economical to walk, are discussed. A tentative hypothesis on the determinants of Ss, which is emphasized to be a speed which has to be studied in detail but is generally avoided in locomotion, is based on a comfort criterion from peripheric afferences and is reflected by the fact that at Ss a running stride costs as much as a walking stride.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8010137 TI - A method for analysis of cellular K-transport mechanisms through thallium (201Tl) uptake in human lymphocytes. AB - Thallium (Tl) is the K-congener with the highest specific affinity to K-binding sites and the largest permeability in K-channels, and its usefulness for analysis of cellular K-transport mechanisms was investigated. The uptake of 201Tl was measured in cultured human lymphocytes (Jurkat cells and EBV-transformed B-cells) after various incubation conditions. In a complete culture medium the half-time of the Tl-uptake was 10 min at 37 degrees C and the steady state accumulation ratio (intracellular/extracellular) was c. 50. The steady state ouabain sensitive uptake was 81% in complete culture medium, it was reduced after substitution with Ringer solution and by a decrease in temperature (from 37 to 22 degrees C). The ouabain resistant uptake was higher at 22 degrees C than at 37 degrees C and it was almost completely inhibited in Na-free or Cl-free solution and by furosemide. The present results indicate that there are only two major routes for K-uptake in lymphocytes and that 201Tl may be a useful substitute for K in the analysis of cellular K-transport mechanisms. PMID- 8010140 TI - Differences in ultrastructural and metabolic profiles within the same type of fibres in various muscles of young and adult rats. AB - Single fibres from tibialis anterior, extensor digitorum longus, gastrocnemius and soleus muscles in young (4-week-old) and adult (35-week-old) Wistar male rats were classified into three types on the basis of their enzyme-histochemical features: slow-twitch oxidative (SO), fast-twitch oxidative and glycolytic (FOG) and fast-twitch glycolytic (FG) fibres. Ultrastructural (volume density of mitochondria: Vmt and Z line width) and metabolic (phosphofructokinase: PFK and succinate dehydrogenase: SDH activities) profiles were measured. PFK activity in all types of fibres was higher in adult rats, and the difference between the two age-groups (adult/young) was largest between FG, FOG and SO fibres respectively. SDH activity and Vmt were lower in adult rats in a similar way in all fibres. A significant positive correlation was observed between the Vmt and SDH activity in both age-groups. This positive correlation was very specific in fast-twitch and slow-twitch fibres. Changes in the Vmt did not relate directly to the changes in fibre cross-sectional area. The overall pattern indicates that glycolytic capacity of fast-twitch fibres in flexor muscles (TA and EDL) is higher than in extensor muscles (GC and SOL), and that oxidative capacity of all types of fibre in extensor muscles is higher than in flexor muscles. These profiles were changed by growth, and may be related to the specific differences in pattern of activity of each skeletal muscle, and may reflect differences in the recruitment order of different muscles. PMID- 8010139 TI - The inotropic mechanism of the phosphodiesterase inhibitor OPC 3911 alone and in combination with rolipram, studied in papillary muscles of ferret and guinea-pig and isolated myocytes of guinea-pig ventricular muscle. AB - OPC 3911 is a potent inhibitor and PDE III is a specific inhibitor in cardiac muscle. The effects of the drug alone and in combination with the non-inotropic PDE IV inhibitor rolipram were analysed using hearts from guinea-pigs and ferrets. OPC 3911 had an EC50 value of 0.1 microM. At 0.1 microM peak force was increased by 50.7 +/- 7.6% (n = 6, P < 0.001), time to peak tension (TPT) reduced by 18.7 +/- 5.6% (n = 6, P < 0.05). Time to half relaxation (THR) was prolonged by 19 +/- 4.2% (n = 6, P < 0.001). After addition of rolipram (30 microM), there was a potentiation of peak force at all concentrations of OPC 3911. At 0.1 microM OPC rolipram increased peak force by 82.8 +/- 8.9% (n = 6, P < 0.001), reduced TPT by 73 +/- 6% (n = 6, P < 0.005) and increased THR by 27 +/- 5% (P < 0.01). OPC 3911 shortened action potential duration (APD) at 50% repolarization by 5.3 +/- 2.5% (n = 6, P < 0.05). Addition of rolipram prolonged APD by 3.7 +/- 2.5% (n = 6, P < 0.05). Second inward current (Isi) was increased at 3 microM OPC 3911 by 46 +/- 6% (n = 6, P < 0.05). The combination of OPC 3911 and rolipram intensified the Isi to 101 +/- 5% (n = 3). Rolipram slowed the rate of restitution and the onset of restitution was prolonged. Relative maximum post-extrasystolic potentiation was reduced in the presence of OPC 3911 from 67 +/- 5% to 45 +/- 6%. Adding rolipram caused potentiation of 55 +/- 6%. OPC 3911 increased the recirculation fraction of activator calcium from 0.36 to 0.42 (n = 10, P < 0.05). After addition of rolipram the recirculation fraction was 0.41 +/- 0.04 (n = 10, P < 0.05). The results suggest that rolipram exerts its potentiating effect on OPC 3911 via an increased Isi. PMID- 8010141 TI - Rapid and large plasma volume decrease upon short-term quiet standing. PMID- 8010143 TI - [Principles to follow with drugs--optically active compounds]. PMID- 8010142 TI - Estimation of lactate release from contracting muscles in man. PMID- 8010144 TI - [Methods of obtaining pure enantiomeric compounds]. PMID- 8010145 TI - [Pharmacology of optically active compounds]. PMID- 8010146 TI - Building structure for the borderline construct. AB - This article overviews the development of the borderline personality disorder construct. In the past 25 years, the borderline personality diagnosis has grown remarkably in clinical usage even as its construct has undergone dramatic shifts in the process. It originated as a type of intrapsychic personality organization that reflected psychoanalytic observations and the hope for long-term curative therapies. It was transformed by descriptive observations into a syndrome whose boundaries with first schizophrenia and then affective disorders became the subject of intense study. More recently, it is recognized as a specific type of personality disorder that communicates substantial information about pathogenesis and that helps guide clinical planning and prognostication. The context dependency of the borderline patient's presentation explains why the diagnosis can often elude recognition. PMID- 8010147 TI - Genetics in borderline conditions. AB - The published and some unpublished studies of the genetic of borderline conditions are reviewed. It appears that the DSM-III-R borderline personality disorder is not genetically transmitted. The evidence for the genetic transmission of schizotypal personality disorder also appears weak. An examination of the 2 personality disorders reveals multidimensionality and heterogeneity. The borderline personality disorder seems to consist of 2 syndromes, an impulsive borderline and an empty borderline syndrome. The schizotypal personality disorder consists of 3 syndromes, one affect constricted/eccentric, one pseudo-psychotic and one paranoiac isolated syndrome. The impulsive borderline, the affect-constricted/eccentric and the pseudo psychotic syndromes seem slightly genetically influenced. The affect constricted/eccentric syndrome appears to be genetically related to schizophrenia. No other Axis I disorders are related to borderline conditions. PMID- 8010148 TI - The concept of borderline conditions: a critical comment on validity issues. AB - It is pointed out that many published empirical studies on the issue of borderline conditions suffer from methodological shortcomings due to the prevailing empiricist simplification of research. Attention is drawn to the fact that the current psychiatric research in classification issues is dominated by an exaggerated quest for reliability at the expense of concern with validity issues. Concepts of operational criteria, polythetic-prototypic systems, and epistemic peculiarities of psychiatric, clinical typification are briefly exposed. It is suggested that future scientific progress in the area of personality research must take into account these general methodological considerations: repotentiate clinical-phenomenological observation, include prototypical approaches, extend studied samples with subjects drawn from the general population and import insights from personality trait research in normal psychology. Some of the claims of Gunderson and Torgersen (this volume) are discussed. PMID- 8010150 TI - What are the borders of borderline personality disorder? AB - It is argued that the usefulness of borderline personality disorder in clinical and research practice is largely because the borders of the diagnosis are so flexible. The diagnosis overlaps with other personality disorders, disturbances of mood and intermittent abnormal behavior. As almost all behavior likely to lead to consultation with mental health professionals is included among the elements of personality disorder, it is not surprising that it is almost the most common condition seen by specialists in the field. An attempt is made to define the borders of the condition in this review. It is concluded that these are so far reaching that they negate the notion that borderline conditions are personality disorders. It is argued that the borderline state is a coaxial diagnosis of personality and mental state disorder and to continue to describe the concept as a personality disorder is wrong and misleading. PMID- 8010149 TI - The temperamental borders of affective disorders. AB - Depending on the population studied, anywhere from half to two-thirds of DSM-III borderline disorders seem to represent subaffective expressions, principally on the border of bipolar disorder. "Borderland" may actually be a better characterization of this large temperamentally unstable terrain with a population prevalence of 4-6% (as compared with 1% for classical bipolar disorder). The temperaments include the dysthymic, irritable, and cyclothymic types which, respectively, coexist with "double depressive", mixed bipolar, and bipolar II disorders; others conform to an anxious-sensitive temperament in continuum with hysteroid dysphoric and atypical depressive disorders. Borderline "stable instability" in these patients appears secondary to affective temperamental dysregulation, which has exacerbated into a protracted emotional storm during a difficult maturational phase in the biography of a given patient. PMID- 8010151 TI - The borderline syndromes of depression, mania and schizophrenia: the coaxial or temperamental approach. AB - When analyzing the diagnostic position of "neurosis", Akiskal found it clinically meaningless because it lacks sufficient phenomenological characterization. In contrast, Tyrer found it meaningful because it explains the heterogeneity of neurotic symptoms. The diagnostic position of "borderline" has been treated analogically by Akiskal and Tyrer. Thus, Tyrer uses the term borderline in a very broad and general sense, while Akiskal again has found it without sufficient phenomenological characterization. Hence, the DSM-III concept of borderline personality disorder includes the temperament borders of affective disorders (melancholic, choleric and sanguine). A closer look at the Tyrer concept of neurosis places it within the melancholic temperament. The choleric temperament covers cyclothymia and the sanguine temperament the subclinical manifestations of mania. The term borderline personality disorders should, then, be restricted to cover the phlegmatic temperament or mild degrees of the schizophrenic spectrum disorders, which is in accordance with ICD-10. PMID- 8010152 TI - Is there any drug treatment of choice for the borderline patient? AB - Psychotropic medication is used extensively in the borderline patient in an effort to treat the cognitive, affective, impulsive-behavioral and anxious fearful symptoms which comprise the state symptoms and trait vulnerabilities of BPD. This paper reviews the efficacy of neuroleptics, antidepressants (TCA, MAOI and SSRI), lithium carbonate, carbamazepine and benzodiazepines against these 4 symptom domains. There is currently no single drug treatment of choice in BPD. Current research supports acute treatment. Maintenance trials are generally lacking or show limited efficacy. A dimensional approach is recommended for clinical practice and future research trials, targeting specific symptom domains with selective medication. Pharmacotherapy should be viewed as a useful adjunct to psychotherapy in the long-term treatment of the borderline patient. PMID- 8010153 TI - Dialectical behavior therapy for borderline personality disorder: theoretical and empirical foundations. AB - Dialectical behavior therapy (DBT) is a cognitive-behavioral psychotherapy developed by Linehan for parasuicidal patients with a diagnosis of borderline personality disorder (BPD). DBT is based on a biosocial theory that views BPD as primarily a dysfunction of the emotion regulation system. The treatment is organized around a hierarchy of behavioral goals that vary in different modes of therapy. In two randomized trials, DBT has shown superiority in reducing parasuicide, medical risk of parasuicides, number of hospital days, dropout from treatment and anger while improving social adjustment. Most gains were maintained through a 1-year follow-up. In one process study testing DBT theory, dialectical techniques balancing acceptance and change were more effective than pure change or acceptance techniques in reducing suicidal behavior. PMID- 8010154 TI - Cognitive therapy in the treatment of patients with borderline personality disorders. AB - Cognitive therapy, originally conceived for the treatment of emotional illnesses, has been successively used also in treating patients with more severe mental disorders. In this article, the results obtained by Shearin & Linehan (this volume) in a few controlled trials of dialectical behavior therapy in patients with borderline personality disorders are discussed. Differences between the treatment approach followed by Shearin & Linehan, which focuses on the modification of specific behaviors, and that favored by the author, which is aimed at restructuring dysfunctional working models of self and environment, are highlighted. In the conclusion it is emphasized that the use of a structured, didactic and cognitive-behaviorally oriented approach focused on personal growth might represent an important and much wanted breakthrough in the treatment of the most disturbed patients with a borderline personality disorder. PMID- 8010155 TI - Ontogenesis of quisqualate-associated phosphoinositide metabolism in various regions of the rat nervous system. AB - The effect of postnatal age on phosphoinositide metabolism per se and on quisqualate-stimulated phosphoinositide metabolism was characterized in synaptoneurosomes prepared from nine different regions of the rat nervous system, namely the brainstem, cerebellum, cerebral cortex, colliculi, hippocampus, hypothalamus, olfactory bulb, spinal cord and striatum. In the hippocampus, striatum, cerebellum, cerebral cortex, brainstem, colliculus and spinal cord, the basal levels of inositol phosphate (inositol-1-phosphate+inositol-4,5 bisphosphate) formation were maximal two days after birth and declined steeply to steady-state levels from the age of 10 postnatal days. Similarly, in the olfactory bulb, basal inositol phosphate synthesis did not significantly change when measured during the period from postnatal day 10 to 42. The extent of [3H] inositol labelling of phosphoinositides as a function of age presented similar profiles when measured in hippocampal, striatal, cerebellar and cerebral cortical synaptoneurosomes, i.e. maximal at perinatal ages and minimal at adult ages. In the hypothalamus, [3H]-inositol labelling of phosphoinositides showed an increase from postnatal day 12 to higher levels from postnatal days 14 to 18 subsequently followed by a dramatic increase from postnatal day 21 to 42. A similar developmental trend was also obtained for basal inositol phosphate synthesis. On the whole, four types of developmental profiles for quisqualate-stimulated inositol phosphate formation (expressed as the percentage of the basal level and as the difference between stimulated and basal levels of radioactive inositol phosphates) were obtained depending on the nervous system region studied. In the early, prenatally developed nervous system regions, namely the brainstem and the spinal cord, no postnatal stimulation peaks of quisqualate-induced inositol phosphate formation were recorded. This was also the case for the colliculi when the stimulation of IP formation was expressed as the difference in basal and stimulated levels of inositol phosphates. Secondly, in the olfactory bulb a region known to possess a continuous capacity for developmental plasticity both structurally and functionally during the first three weeks of postnatal development, a simultaneous sustained high level of quisqualate stimulation of phosphoinositide metabolism (fluctuating around 200% of the basal level) during the early postnatal period was evident. Thirdly, in regions of the central nervous system like the cerebellum, cerebral cortex, hippocampus and the striatum known to undergo intense developmental activity during the first two postnatal weeks, peaks of quisqualate-stimulated phosphoinositide metabolism were initially detected around the first week after birth in each of these brain areas.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8010156 TI - Impaired neurogenesis by methylazoxymethanol in newborn rats results in transient reduction of ornithine decarboxylase and polyamines in the cerebellum, but not in the olfactory bulbs. AB - Polyamines and the key enzyme for their biosynthesis, ornithine decarboxylase (ODC) play an important role in the control of neuronal proliferation and differentiation. Exposure to agents that interfere with normal cell maturation is expected to result in alteration of neuronal ODC developmental pattern. We have administered to newborn rats, about 6 and 30 hr after birth, 20 mg/kg of methylazoxymethanol acetate (MAM), an agent able to selectively kill dividing cells and we have evaluated ODC activity and polyamine levels in the cerebellum and ODC activity in the olfactory bulbs at various developmental stages starting from postnatal day 4 (PD 4) until PD 28. Cerebellar weight decreased by 22-50% at the different developmental stages in MAM-treated animals. A decline in ODC specific activity was observed at PD 4 and a decrease of putrescine levels at PD 4 and PD 6 in the cerebellum. At PD 10, however, both ODC activity and putrescine level were increased in MAM-treated animals. Spermidine levels were never affected by the treatment, while spermine was significantly decreased at PD 6 and PD 8. These results demonstrate that altered ontogenetic patterns of ODC activity and polyamine levels are the consequence of disturbance of the normal process of brain maturation. No significant differences in specific ODC activity were noticed in the olfactory bulbs of MAM-treated rats. This may be related to the more widespread time-span of neurogenesis in this region, a fact that is also revealed by the higher ODC activity constitutively expressed at times in which neurogenesis has ended in the rest of the brain. PMID- 8010157 TI - Developmental profiles of ornithine decarboxylase activity in the hippocampus, neocortex and cerebellum: modulation following lead exposure. AB - Ornithine decarboxylase (ODC) is a growth-associated enzyme which is critical for cell growth and transformation. ODC activity follows a specific ontogenetic pattern of activity in distinct brain regions according to their developmental stage. Perturbations in the pattern of ODC activity have been associated with brain damage including arrested cerebral growth. Modulations in the pattern of ODC activity were examined in the hippocampus, neocortex and cerebellum of neonatal rats (PND 3, 6, 9, 15) exposed via the dam to 0.2% lead-acetate (Pb2+ prenatally (gestational day 13 to birth), postnatally (PND 1-15) or perinatally (gestational day 13 to PND 15). Prenatal exposure to Pb2+ perturbed the profile of ODC activity in all three brain regions examined, while postnatal exposure to Pb2+ resulted in prolonged stimulations of ODC activity in the cerebellum. Following prenatal exposure, these effects were manifested as a stimulation of ODC activity in the hippocampus, a repression of activity in the neocortex and a combination of these effects in the cerebellum. Perinatal exposure to Pb2+ transiently modulated the pattern of ODC activity similarly in all three brain regions, in a characteristic manner irrespective of their developmental stage. These Pb(2+)-induced modulations of ODC activity suggest that polyamine-dependent processes may play a significant role in the manifestation of Pb(2+)-induced neurotoxicity dependent upon developmental factors at specific exposure periods. PMID- 8010158 TI - Different omega-conotoxins mark the development of Swiss Webster mouse cortex suggesting N-type voltage sensitive calcium channel subtypes. AB - omega-GVIA conotoxin has been used to mark presynaptic N-type voltage sensitive calcium channels (VSCC). Litzinger et al. used omega-conotoxin binding to describe a critical period of neurodevelopment in Swiss Webster mice between postnatal days (PND) 11 and 14, which appears to be important to the initiation of proper final development of the central nervous system. In this study, we compare how three different omega-conotoxins (i.e. GVIA from Conus geographus, MVIIA from Conus magus, and RVIA from Conus radiatus) mark N-type VSCC during this critical period in Swiss Webster mouse cortex. 125I-GVIA was bound to Swiss Webster mouse cortex synaptosomal membrane fractions at postnatal days 8 and 14. 125I-GVIA binding displacement curves were obtained by incubating membranes with increasing concentrations of unlabeled GVIA, MVIIA, and RVIA. Displacement curves and IC50 were calculated for each of these three omega-conotoxins, and then compared. At PND 14, GVIA, MVIIA and RVIA were able to displace greater than 95% of 125I-GVIA binding. At PND 8, however, MVIIA was only able to displace 83% of 125I-GVIA binding, and RVIA was only able to block 84%. The IC50 does not appear to change significantly during this period of development for any of the omega conotoxins. The inability of MVIIA and RVIA to completely block 125I-GVIA binding in pre-critical period Swiss Webster cortex denotes an alteration in the composition of N-type VSCC binding sites. With this data, we have suggested the presence of subtypes of the N-type VSCC in the cortex of pre-critical period Swiss Webster mouse. PMID- 8010160 TI - Leptomeningeal and skin fibroblasts: two different cell types? AB - Leptomeningeal and skin fetal (E16-17) fibroblasts were subcultured in vitro either in DMEM/F12 basal medium (with or without 10% FCS) or in astroglial conditioned medium (ACM). Both populations were characteristically composed of flat, undifferentiated, fibronectin(+), GFAP(-)cells where cultured in fetal serum supplemented basal media. When exposed to ACM leptomeningeal cells developed a population of thin, elongated, fibronectin(+) cells with radial type long processes while skin fibroblasts did not show significant changes in their characteristic morphotype. Exposure to db cAMP in basal medium resulted within 3 hr in their transformation to an astrocytic-like morphotype characterized by a condensed soma and multiple, short processes. Twenty-four hours later skin fibroblasts had returned to their flat appearance while leptomeningeal ones showed elongated, radial-like forms. Results indicate the possible existence of different receptors (to ACM factors) and/or cytoskeletal properties, and suggest that ACM-reactive fibroblasts of leptomeningeal origin represent a different cell type from those of skin origin. The hypothetical role of leptomeningeal cells during brain development is considered. PMID- 8010159 TI - Thyroidal stimulation of tubulin and actin in rat brain cytoskeleton. AB - In cultures of neonatal rat brain cells, labeled with 35S-methionine in the presence or absence of triiodothyronine (T3), the hormone promoted a significant enhancement of labeled tubulin and actin in the insoluble fraction (30,000 g pellet) of cell homogenate. To identify the specific sub-cellular fraction associated with this induction, organ cultures of 1 day rat cerebra were labelled with 35S-methionine in the presence and absence of T3 and the insoluble fraction (30,000 g pellet) was subfractionated into mitochondria, plasma membrane and cytoskeleton. Analysis of the labeled proteins by SDS-PAGE, autoradiography and densitometry revealed a T3-induced increase of 50-80% for both tubulin and actin, only in the cytoskeleton fraction without any significant effect on the other fractions. Similar results were obtained when plasma membrane or cytoskeleton were isolated directly from labeled cerebrum by conventional methods instead of fractionating from the 30,000 g pellet. Analysis of relative stimulation of labeled tubulin and actin by T3 in cytoskeleton fraction derived from primary cultures of neuronal (N) and glial (G) cells labeled with 35-methionine show that the stimulatory effect is predominantly on the N cells. Studies on the kinetics of induction of labeled tubulin and actin by T3 in the cytoskeleton fraction prepared from cerebra labeled with 35S-methionine for 2, 8 and 18 hrs revealed no significant difference at 2 hrs; at 8 hrs, an increased incorporation into both tubulin and actin was reproducibly seen in the controls relative to T3-treated samples.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8010161 TI - Muscarinic cholinergic receptor regulation and acetylcholinesterase inhibition in response to insecticide exposure during development. AB - Neonatal rats were exposed to parathion, an acetylcholinesterase inhibiting organophosphorus pesticide, during a rapid phase of cholinergic receptor development. Rats were given subcutaneous injections of 1.5 mg/kg/day from postnatal days 8-20. The immediate effects of subchronic developmental exposure were assessed in 21-day-old animals and more persistent effects assessed in 36 day-old animals. There was a 61% inhibition of acetylcholinesterase and a 27% decrease of muscarinic receptor density in 21-day-old treated rats. The reduction in receptor density was dose-dependent and a significant correlation was found between the level of acetylcholinesterase inhibition produced by parathion and the reduction in receptor density. It was estimated that a minimum of at least 15% prolonged inhibition of forebrain acetylcholinesterase by parathion was necessary to reduce receptor density. Regional analyses of receptor autoradiograms of 21-day-old animals indicated muscarinic receptors in the cortex and hippocampus were preferentially lost. The anterior thalamus was notable in having a high density of cholinergic receptors which were unaffected by parathion treatment. No changes were found in the affinity of [3H]QNB for the receptor or in the binding of the agonist, acetylcholine, n competition binding studies. AChE activity and muscarinic receptor density returned to normal after a 16 day recovery period. Parathion treated animals were growth inhibited but, growth retardation induced by undernutrition did not alter receptor density or affinity of QNB for muscarinic receptors. Thus, the transient decrease in receptor density in parathion exposed animals was similar to the response previously observed in adults and was not secondary to growth retardation or undernutrition. Receptor densities and acetylcholinesterase levels were regulated back to normal values after a 16 day recovery period in spite of the perturbation of cholinergic function during cholinergic synapse and receptor development. PMID- 8010162 TI - Characterization of the response of growth and differentiation to lipoproteins and agents affecting cholesterol metabolism in murine neuroblastoma cells. AB - Treatment with mevinolin, a competitive inhibitor of HMGCoAR, the key enzyme of isoprenoid metabolism, causes the arrest of proliferation and the differentiation of a neuroblastoma cell line (N18TG2). Mevalonate and high density lipoproteins partially restore growth. Cholesterol synthesis in the presence of mevinolin remains active, because in these cells the key enzyme HMG-CoA reductase is not completely inhibited by this drug. The fact that cell growth is reduced, while cholesterogenesis remains active, suggests that mevinolin acts by interfering with the synthesis of some unknown compound, other than cholesterol, which is necessary for proliferation. PMID- 8010164 TI - How readable are the hospital information leaflets available to elderly patients? AB - The readability of 70 hospital information leaflets was compared with that of outside publications. Clarify of language was assessed by calculation of a 'reading score' for each document using the Gunning FOG test. Layout was assessed in terms of typeface, style of print and use of illustrations. Reading scores were generally satisfactory and illustrations were used effectively in most cases. However, seven (10%) of the leaflets had scores of 14 and above (equivalent to the British Medical Journal). Only 12 (17%) of the leaflets met the recommendations of the Royal National Institute for the Blind for size of typeface. The Gunning FOG test provides a reasonable assessment of readability. Documents scoring 12 and over may be incomprehensible, particularly to elderly patients. PMID- 8010163 TI - Bradyphrenia and parkinsonism. PMID- 8010165 TI - Unsuspected bronchospasm in association with topical timolol--a common problem in elderly people: can we easily identify those affected and do cardioselective agents lead to improvement? AB - The extent of impairment of respiratory function in a group of 52 elderly, glaucomatous patients receiving topical timolol therapy was investigated. To predict those patients who were likely to benefit from changing therapy, symptoms were elicited by direct questioning, and lung spirometry was measured before and after inhalation of salbutamol. Changing from timolol to either pilocarpine or the cardioselective betaxolol produced improvement in lung function tests. Mean peak flow increased from 278 l/min to 328 l/min (p < 0.001), forced expiratory volume in 1s (FEV1) from 1.66 l to 1.85 l (p < 0.001) and forced vital capacity (FVC) from 2.41 to 2.64 l (p < 0.001). Spirometry in a control group of 20 subjects was unchanged. Nineteen of 47 patients demonstrated a clinically significant (defined as 15% or more) increase in all values of lung function tests. Change to pilocarpine or betaxolol was equally effective in producing improvement but betaxolol had fewer side-effects. The presence of exertional dyspnoea, cough with sputum, raised dyspnoea score and improved lung function tests after salbutamol identified those patients experiencing clinically significant bronchospasm with an 89% specificity and 74% sensitivity. PMID- 8010166 TI - Clinical features and prognosis of hepatocellular carcinoma in Britain in relation to age. AB - A retrospective review of 110 cases of hepatocellular carcinoma (HCC) from the North East of England was undertaken to examine clinical features and prognosis in the 52 patients 65 years of age or more at presentation in comparison with 58 patients under 65. Symptoms and signs at the time of presentation were similar in the two age groups. Only 25% of patients were known to be cirrhotic at the time of presentation, but this increased to 75% after investigation. Although tumour stage at diagnosis was no worse in the elderly group, these patients received less intensive investigation and were significantly more likely to receive conservative therapy (p = 0.03). Although median survival was significantly worse in those aged > or = 65 years than in those < 65 years (10.5 and 18.5 weeks respectively; p = 0.02) this adverse effect disappeared when adjusted for the effects of treatment. PMID- 8010167 TI - Age and clinical characteristics of 1433 patients with lung cancer. AB - A review has been conducted of 1433 patients treated by the Lung Cancer Unit of our hospital to assess the association of age with clinical characteristics of patients with lung cancer. The factors evaluated were tobacco, stage of disease, treatment and survival of patients treated surgically. A comparison was made of patients aged 65 or less with those over 65. There was a similar prevalence of smokers in both age groups. The stage of disease at time of diagnosis was similar (33% of the patients aged 65 or less were Stage I or II versus 37% of the older patients). The distribution by histological type showed significant differences (p < 0.05) with a higher percentage of squamous carcinoma in the younger group (54% versus 44%). Surgery was performed in 30% of the patients aged 65 years or less but only in 19% of the older cases (p < 0.05). Among those patients treated surgically there was no difference in the survival of younger and older patients. PMID- 8010168 TI - Euthanasia: the Dutch experience. AB - Although rules about euthanasia have been developed in the Netherlands, euthanasia has not been legalized. We review the historical aspects of euthanasia, its definition and why no distinction is now made between active and passive euthanasia in the Netherlands. The guidelines for euthanasia, in use in the Utrecht University Hospital, are presented and the result of some studies on euthanasia is discussed. Non-treatment decisions were taken in 17.5% of all deaths in 1990 but only 1.8% of all deaths were the result of euthanasia. Life terminating acts without explicit and persistent request of the patients occurred in 0.8% of all deaths. The most common reasons for requests for euthanasia were loss of dignity in 57%, pain in 46%, distressing mode of dying in 46% and being dependent on others in 33%. Of all medical decisions concerning the end of life 79% related to patients older than 65 years. The guidelines for euthanasia developed in the Netherlands support both patient and physician in the request for euthanasia. PMID- 8010169 TI - Detrusor hyperreflexia--are there two types? AB - The concept that elderly patients with urinary incontinence due to detrusor hyperreflexia can be divided into two groups with differing natural histories on the basis of the detrusor contractility found on cystometry is reassessed. Thirty patients shown to have hyperreflexia on urodynamic study for persistent urinary incontinence following a recent neurological lesion had their contractility measured by the suggested criteria of the residual urine following a hyperreflexic contraction and the rate of increase of detrusor pressure. The consistency of contractility on cystometry was also measured by repeating this three times on the same occasion. A spectrum of values for the post-contraction volumes and the rate of increase of detrusor pressure was found. On repetitive cystometry 11 out of 30 patients showed a variable post-contraction residual volume. While impaired contractility is common in detrusor hyperreflexia, the concept of two subgroups is not supported by these results. In some patients cystometric measures of contractility vary considerably on repeating the study on the same occasion. PMID- 8010170 TI - Functional profiles of healthy older persons. AB - To learn whether the percentage of time spent at different functional levels varies as a function of age, we studied 44 older (mean age 70 years) and 46 younger (mean age 27 years) urban, community-dwelling volunteers who participated in a study of normative ageing of the cardiovascular system. Each subject completed one 24-hour activity diary which was coded using a standardized scoring system for functional activity levels and energy levels. Compared with younger persons, older persons spent larger percentage of their day performing basic (BADLs) and intermediate activities of daily living (IADLs) and less time in physical advanced activities of daily living and sleeping. Older women spent more time than younger women performing BADLs and more time than younger women or older men performing IADLs. These findings support the concept of functional changes associated with healthy ageing which may be more pronounced in women. Our results may also reflect a cohort effect that may disappear with the change of traditional sex roles. PMID- 8010171 TI - Nutritional status of elderly patients during recovery from chest infection and the role of nutritional supplementation assessed by a prospective randomized single-blind trial. AB - We examined changes in the nutritional status of elderly patients with chest infection for a period of 3 months after discharge from hospital, including the effects of nutritional supplementation on well-being and functional status as well as on nutritional indices. Eighty-one subjects admitted to an acute medical ward aged 65 years and over with chest infection were recruited consecutively, and randomized to receive supplement (500 ml of Ensure liquid daily) for 1 month, or no supplement, on discharge. Assessment at baseline, 1, 2 and 3 months included a questionnaire to determine health, mental and functional status, and anthropometric measurements. Biochemical nutritional status was assessed at baseline, 1 and 3 months, and dietary intake (24 h recall method) at 1 and 3 months. During recovery, both supplement and non-supplement groups showed improvement in various measures of well-being and biochemical status. In addition, the former group showed improvement in more anthropometric measurements, in thiamine and pyridoxine status, while the non-supplement group showed a lower level of functional ability after 3 months. Various measures of well-being and biochemical status of the water-soluble vitamins were better in the supplement groups. We conclude that nutritional supplementation may have a role in helping elderly patients to recover from chest infections. PMID- 8010172 TI - Relationship between nutritional status and immune function of elderly people. AB - Thirty-four malnourished subjects between the ages of 61 and 97 years were given appropriate food supplement(s) for a period of 6 consecutive months. They were followed for a subsequent 6 months during which time there was no nutritional intervention. Nutritional assessment and immunological evaluation were performed at 0, 6, and 12 months. Nutritional assessment included anthropometry, biochemistry, and clinical examination. Immunological evaluation included serum complement C3 concentration, delayed cutaneous hypersensitivity skin test, and the enumeration of total lymphocytes, rosetting T-cells, CD4+ cells, and CD8+ cells. Immune function improved by the end of the supplementation period. Six months of nutritional supplementation significantly increased the percentage of lymphocytes represented by mature T-cells. PMID- 8010173 TI - Unrecognized visual problems amongst residents of Part III Homes. AB - A survey of visual function and ophthalmic pathology of 100 residents of three residential homes for elderly people was carried out in Lambeth London. The main pathologies were cataracts detected in half of the subjects (6% were referred for extraction) and chronic simple glaucoma in 17%. Unrecognized significant refraction errors were found in 34% of subjects. Only eight of the 14 residents eligible for blind or partially sighted registration had been already registered. It is suggested that old people entering residential care should have a competent geriatric or psychogeriatric assessment and, in addition to the annual general practitioner assessment for residents aged 75 and over, regular ophthalmic evaluation should be offered to residents of homes. PMID- 8010174 TI - Heart rate and blood pressure responses to carotid sinus massage in healthy elderly subjects. AB - The purpose of the study was to define heart rate and blood pressure responses to supine and upright carotid sinus massage in healthy elderly subjects and thus to establish the validity of current diagnostic criteria for carotid sinus syndrome in this age group. Twenty-five healthy asymptomatic subjects (61-87 years) had carotid sinus massage carried out following a standardized technique employing previously defined criteria for abnormal heart rate and blood pressure responses: 3 s asystole and a 50 mmHg fall in systolic blood pressure independent of any heart rate slowing (after intravenous atropine). No cardioinhibitory responses of greater than 3 s were documented. The mean maximal cardioinhibitory response was 1038 +/- 195 msec. Right-sided responses were more marked than left when upright (1040 +/- 202 vs. 946 +/- 135 msec; p < 0.01) but not when supine (1094 +/- 215 vs. 1073 +/- 194 msec; NS). After atropine three subjects (12%) had a significant vasodepressor response when upright, but none when supine. The mean maximal vasodepressor response was 21 +/- 14 mmHg. Right-sided blood pressure responses were more marked than left (p < 0.01). There was no fixed relationship between maximum heart rate slowing and the degree of vasodepression during massage (range 2-80 msec/mmHg). The diagnostic criteria for heart rate and blood pressure responses in carotid sinus syndrome are appropriate for supine carotid sinus massage in elderly subjects. Asymptomatic vasodepressor responses occur in a small proportion of healthy elderly when upright. PMID- 8010175 TI - An age-related investigation of urinary tract symptoms and infection following urodynamic studies. AB - One hundred and thirty-nine patients undergoing urodynamic investigation were studied. Urine samples taken at the time of the test and at 72 hours afterwards were cultured and data on symptoms following the test were collected. The overall infection rate was 15.8%. Men and women aged over 70 years were no more likely than younger subjects to become infected. A high residual urine volume was not associated with an increased risk of infection. The only clinical feature associated with infection following the test was an increase in incontinence. These findings were all in contradiction to previous studies on smaller numbers of patients. PMID- 8010176 TI - The outcome of a medical examination for applicants to Leicestershire homes for older people. AB - Medical screening of applicants to residential homes for older people has been shown to redirect inappropriate applications, although other outcomes have not been reported. This study assessed 117 applicants, of whom 63% were medically examined and offered medically directed interventions if indicated. All applicants were then reassessed at 6 and 12 weeks. No significant differences in survival, or changes in cognitive score, disability, incontinence or self reported health were found between intervention and control groups. Intervention did redirect some applicants to more appropriate care and resulted in significantly greater improvements in morale. These results raised the question of whether it is appropriate for medical assessment to be used primarily to enforce admission criteria in the absence of other significant health benefits. However, the greater improvements in morale of the intervention group did indicate some benefit from the medical examination. PMID- 8010177 TI - Is low blood pressure in elderly people just a consequence of heart disease and frailty? AB - Low blood pressure has been associated with increased mortality in older people, but it is unclear whether the hypotension is a risk in its own right or just a marker of disease. In this study we investigated the extent to which those in the lowest decile of systolic and diastolic pressures could be predicted by measures of cardiovascular disease and frailty. We studied 782 people 70 years and over drawn from the only group of general practices in a rural township. Hypotension was defined separately for systolic and diastolic blood pressures as a pressure less than the tenth percentile for the sample as a whole. This was a systolic pressure of < or = 122 mmHg and a diastolic pressure of < or = 68 mmHg. There was a significant relationship between low systolic blood pressure and male sex, history of myocardial infarction by questionnaire and low body mass index (BMI), and between low diastolic pressure and male sex, history of angina and myocardial infarction, use of one or more hypotensive drugs, low BMI, low corrected arm muscle area, low self-maintenance score and the use of two or more home services. There was no association with ECG abnormalities. In the multivariate analysis only 4.2% of those with low diastolic pressure and none of those with low systolic pressure could be correctly classified. Hypotension in old age is only partially explained by established cardiovascular disease and frailty. PMID- 8010178 TI - Review: Binswanger's disease, leukoaraiosis and dementia. PMID- 8010179 TI - Standardized functional assessment scales for elderly patients. PMID- 8010180 TI - Follow-up of a controlled trial of domiciliary stroke rehabilitation (DOMINO Study). AB - The DOMINO study compared domiciliary and hospital-based rehabilitation services for stroke patients after discharge from hospital, stratified by the hospital ward at discharge. No difference between the services had been found at 6 months, but home therapy was better than outpatient department therapy at improving household ability and leisure activity in the patients discharged from the Stroke Unit (SU), and attendance at a day hospital may have been better than a domiciliary service at preventing death or institutionalization for patients discharged from Health Care of the Elderly (HCE) wards. We report the follow-up of the patients between 6 months and 1 year after discharge, during which time few patients received further treatment and little change in health or function occurred. Over this period the benefits of domiciliary rehabilitation in the SU group were lost, largely because the patients who had been treated in outpatient departments continued to improve. Between 6 months and 1 year the numbers of HCE patients in the two treatment groups who died or were institutionalized were similar, but the advantage of day hospital attendance was still evident at 1 year. PMID- 8010181 TI - Transduction of resistance to Imipenem, Aztreonam and Ceftazidime in nosocomial strains of Pseudomonas aeruginosa by wild-type phages. AB - Two wild-type bacteriophages, designated AP-2 (for P. aeruginosa phage) and AP 12, have been isolated and propagated from two multiple drug resistant strains of P. aeruginosa. Both phages were found to transduce Imipenem- (IMI), Aztreonam- (AZA) and Ceftazidime- (CTZ) resistance as well as resistance determinants to other drugs. Genetic analysis showed that resistance determinants to newest anti pseudomonal antibiotics IMI, AZA and CTZ could be separated by transduction. Thus the resistance to these antibiotics is presumably coded by different genes. In some transductans also the presence of the tra+ has been demonstrated, indicating that they can transfer the resistance to other strains by conjugation. PMID- 8010182 TI - Comparison of virulence for guinea pigs and mice of different Coxiella burnetii phase I strains. AB - Virulence of four Coxiella burnettii phase I strains associated with acute (Nine Mile and Luga strains) and chronic (S and Priscilla strains) forms of Q fever, respectively, for outbred guinea pigs and inbred BALB/c mice was compared. In guinea pigs exposed to infectious aerosol, virulence of the strains Nine Mile, Luga and S was similar, because they all caused lethal infection and high febrile reaction (FR). By contrast, exposure to similar doses of the strain Priscilla resulted in the non-lethal infection manifested only by low, dispersed and protracted FR during a 20 day-period of observation. Lower virulence of the strain Priscilla than of the strains Nine Mile and S was observed also in guinea pigs infected intraperitoneally (ip). In mice, comparable degree of multiplication in the spleen on day 6 post ip infection was observed with the strains Nine Mile, Luga and S, but not with the strain Priscilla, namely when lower infectious doses were used. Whereas the highest doses (10(7) EID50) of the strains Nine Mile and S were lethal for mice during the second week post infection (p.i.), the strains Luga and Priscilla did not kill mice with 10-times lower (10(6) EID50) doses. At the same time agglutination antibody response detected 4 weeks p.i. was very similar in guinea pigs with all strains under study and in mice it did not differ markedly, reflecting the infectious dose used. PMID- 8010183 TI - The complex formation of influenza virus envelope glycoproteins with outer membrane proteins of Neisseria meningitidis or Borrelia burgdorferi. AB - The isolation of influenza virus envelope glycoproteins was achieved by one-step procedure consisting of treatment of purified virus with zwitterionic detergent and separation of viral constituents by sucrose density gradient centrifugation. Viral glycoproteins and proteins of outer membrane of N. meningitidis or B. burgdorferi formed complexes after removal of the detergent by dialysis. Complexing of viral glycoproteins and bacterial proteins was monitored by gel chromatography on Sepharose 6B, polyacrylamide gel electrophoresis and electron microscopy. It was demonstrated by immunoblot analysis, that virus-spirochete complexes elicited formation of antibodies in mice directed against osp A and osp B of spirochete, as well as against viral glycoproteins, respectively. PMID- 8010184 TI - Study of T-lymphocyte subpopulation in HBsAg-positive pregnant women. AB - Pregnancy can alter the immunologic status, especially it can suppress the cell mediated immunity. The super-imposition of viral infection on the pregnant state leading to further immunosuppression was the subject of this study. 1109 pregnant women were enrolled and screened for hepatitis B surface antigen (HBsAg) carrier status; 25 HBsAg carriers were identified by reverse passive haemagglutination assay (RPHA) and their T-lymphocyte subsets were determined using monoclonal antibodies (MoAbs). It was observed that there was a significant fall in the total T-cells (CD3+) and T-helper cells (CD4+) in the pregnant HBsAg carriers accompanied by a rise in the T-suppressor cell (CD8+) population as compared to HBsAg-negative pregnant controls. These data demonstrate a weakening of immune status in pregnancy associated with HBsAg carrier state. PMID- 8010185 TI - Inhibition of hepatic extramedullary haemopoiesis by nucleoprotein of heterologous rotavirus strain in infant mice. AB - Infant mice (NMRI strain) showed the inhibition of hepatic extramedullary haemopoiesis by oral inoculation of a 100 ID50 dose of EB rotavirus and nucleoprotein of SA-11 rotavirus (serotype 3). The extramedullary haemopoiesis was observed by oral inoculation of surface protein VP7 of SA-11 rotavirus and in control (placebo administered) mice. PMID- 8010186 TI - Essaouira and Kala iris: two new orbiviruses of the Kemerovo serogroup, Chenuda complex, isolated from Ornithodoros (Alectorobius) maritimus ticks in Morocco. AB - Essaouira and Kala Iris viruses were isolated from Ornithodoros (Alectorobius) maritimus ticks parasitizing yellow-legged gulls (Larus cachinnans) on the coast of Morocco in 1979 and 1981, respectively. Serological evidence indicates that these two viruses are new members of the Chenuda complex within the Kemerovo serogroup of the genus Orbivirus. Ecological, pathological, morphological, and physicochemical properties are compatible with these findings. The infectivity of these viruses for man and animals, including seabirds, remains unknown. PMID- 8010187 TI - Cholinergic system in experimental rabies in mice. AB - A defect in cholinergic synaptic neurotransmission could explain the neuronal dysfunction that has been observed in rabies. The enzymatic activities of choline acetyltransferase (ChAT), acetylcholinesterase (AChE), and enolase were assessed in the brains of rabies virus strain CVS-infected and uninfected mice. No statistically significant differences in activities of ChAT, AChE, or enolase were observed in the cerebral cortex or hippocampus of moribund CVS-infected mice versus controls. Binding to muscarinic acetylcholine receptors, which was assessed with 3H-labelled quinuclidinyl benzylate (QNB), was also not significantly different in the cerebral cortex or hippocampus of CVS-infected mice and uninfected controls. The studies suggest that dysfunction of the cholinergic system is unlikely of fundamental importance in this mouse model of rabies. PMID- 8010188 TI - Comparison of antigenic properties of three interferon (IFN)-alpha 2 subvariants and establishement of a quantitative IFN-alpha 2 ELISA. AB - Three subvariants of human IFN-alpha 2 (2a, 2b, 2c) were found antigenically highly homologous, using a panel of specific monoclonal antibodies (MoAbs) directed to seven epitopes. Only in the region 30-41 IFN-alpha 2c showed some difference from the corresponding structures of subvariants 2a and 2b. An universal sandwich ELISA for the quantification of all subvariants of human IFN alpha 2 was designed. A major increase in sensitivity of the immunoassay could be achieved, when polyclonal antibody to IFN-alpha 2 was combined with a mixture of three MoAbs to distinct sites of IFN-alpha 2, compared to the combination of a polyclonal antibody with a single MoAb. The sensitivity of the established ELISA ranged between 1-10 units/ml of IFN-alpha 2 and no cross-reactivity with IFN alpha 1, -beta, or -omega 1 could be observed. We estimated the content of IFN alpha 2 to about 56% in leukocyte IFN-alpha or to about 72% in Namalwa IFN-alpha. PMID- 8010189 TI - Rhesus monkeys infected with hepatitis E virus (HEV) from the former USSR are immune to subsequent challenge with an Indian strain of HEV. AB - Two rhesus monkeys (M. mullata) of approximately two years of age were inoculated intravenously with a 10% suspension of hepatitis E virus (HEV) positive stool from Kirghistan as evidenced by immuno-electron microscopy. Evidence of HEV infection was demonstrated by rise in serum alanine transaminase (ALT) levels and seroconversion of these monkeys to anti-HEV after 1-1/2 months post-inoculation as evidenced by immunoblot. One year after the primary inoculation, these monkeys were challenged with an Indian strain of HEV. No rise in serum ALT levels was noted during an observation period of 6 months. The same inoculum produced HE in two rhesus monkeys. The results showed that strains from India and Kirghistan were antigenically closely related and rhesus monkeys infected with one strain of virus were immune to another strain. PMID- 8010190 TI - Eperythrozoon--a lesson for arbovirologists. AB - Eperythrozoon was detected in suckling mice inoculated with a suspension of nymphal Ixodes ricinus ticks. The organism was filterable through 220 nm Millipore membranes, moderately sensitive to diethyl ether, pathogenic to suckling but not to adult mice when given intracerebrally, intraperitoneally or subcutaneously, and mimicked an arbovirus. Eperythrozoon should be considered as an agent potentially interfering with experiments performed on laboratory mice. PMID- 8010191 TI - Nucleotide sequence of the 7 K gene of Helenium virus S. AB - The sequence of 380 nucleotides upstream of the start codon of the open reading frame (ORF) of the coat protein of the carlavirus Helenium virus (HelVS) was determined from cloned cDNA. This portion of the viral RNA contained one complete ORF encoding a protein of 7 K which had homology with similar sized proteins from other members of the carla- and potexvirus groups. Sequence data was also obtained beyond the start codon of the 7 K ORF into what was presumed to be the 12 K protein gene of the previously identified triple gene block of carla- and potexviruses. Significant sequence similarity of 46.3% and 41.6% was evident at the amino acid level with the equivalent regions of the 12 K proteins of potato virus S, Andean strain (PVSA) and potato virus M (PVM), respectively, with 25.4% similarity detected with the equivalent region of potato virus X (PVX). PMID- 8010192 TI - Managed care and the radiologist: expectations and future trends. AB - Our health care system, burdened by excessive costs and unprecedented growth, is in need of reform. How to carry out such reform and achieve an acceptable balance between quality and cost of care remains the dilemma. Attempts to control costs and limit growth have, in recent years, produced a disturbing trend in the quality and availability of health care benefits, focusing on benefit reduction without addressing resource utilization or quality of care. The result of these efforts? Persons who have health care insurance are paying more for basic plans and reduced benefits; others are either uninsured or underinsured. Health care benefits continue to be the fastest growing component of business expenses, strengthening the perception of diminishing competitiveness in the world market. The formation of smaller businesses offering no health care benefits continues to be problematic. PMID- 8010194 TI - The radiologist in the 1990s: new practice expectations and management responsibilities. AB - Radiology has enjoyed an enviable position among medical specialties during the past two decades. Unprecedented developments in new technology expanded its horizons, and the volume of radiologic procedures increased far more than overall growth in health care services. The attendant increase in relative and absolute health care spending on radiologic services has cast radiology as a prime target for restrictions, cutbacks, and limitations in an era of managed care and national concern for reining in the growth of health care spending. A strategic response by radiologists requires an understanding of the implications of structural change in health care delivery systems and payment systems. To meet the imperatives of the 1990s, radiologists must do far more than perform and interpret imaging procedures: they must learn to work as efficient managers of health care imaging resources and to organize their practices for effective contracting and service delivery for patients in managed care systems. PMID- 8010195 TI - Hepatic adenoma: MR characteristics and correlation with pathologic findings. AB - OBJECTIVE: The purpose of this study was to describe the MR appearance of hepatic adenomas and correlate the MR imaging features with pathologic findings. MATERIALS AND METHODS: MR examinations were performed in 14 patients with 66 hepatic adenomas. The diagnosis of hepatic adenoma was proved pathologically in nine patients (22 lesions). In five other patients (44 lesions), who had type I glycogen storage disease and were known to be at risk for hepatic adenomas, the diagnosis was established by repeated sonographic examinations that showed stability, reduction, or resolution of hepatic tumors. T1- and T2-weighted spin echo MR images obtained at 1.5 T were retrospectively reviewed for the signal intensity of the lesions relative to liver, the signal pattern, the presence of a capsule, and the presence of hemorrhage. Histopathologic specimens (22 lesions) were reviewed for fat content (graded 0-3), the presence of a capsule, and the presence of hemorrhage. RESULTS: On T1-weighted images, 51 (77%) of 66 lesions were hyperintense, 11 (17%) were hypointense, and four (6%) were isointense with respect to liver. On T2-weighted images, 49 (74%) of 66 lesions were hyperintense, 12 (18%) were isointense, and five (8%) were hypointense. Sixty-one (92%) of 66 lesions were heterogeneous. Eleven (17%) of 66 lesions were hemorrhagic. Of the 22 lesions reviewed histopathologically, 17 were hyperintense on T1-weighted images; 15 of these had a fat content of grade 2 or 3 and two had hemorrhage. All 15 lesions that had a fat content of grade 2 or 3 were hyperintense on T1-weighted images. CONCLUSION: Hepatic adenomas have a variable MR appearance but most often are hyperintense with respect to liver on T1- and T2 weighted images. The high signal intensity often relates to the increased fat content of these lesions. PMID- 8010193 TI - Color Doppler sonography of transjugular intrahepatic portosystemic shunts (TIPS). AB - Transjugular intrahepatic portosystemic shunts (TIPS) have largely replaced surgically created shunts in the treatment of life-threatening sequelae of portal venous hypertension [1-5]. Conventional duplex and color Doppler sonography are proving to be useful tools in the assessment of the stents and their associated hemodynamic changes [2-5]. A thorough Doppler survey before and immediately after TIPS placement provides a baseline for evaluation of shunt function and procedure related complications. Routine follow-up studies at regular intervals after the procedure provide noninvasive assessment of shunt patency and late complications. This pictorial essay illustrates the anatomic and hemodynamic abnormalities present with portal hypertension before TIPS and discusses the expected duplex and color Doppler findings after TIPS. The sonographic characteristics of immediate and delayed complications, as well as potential diagnostic pitfalls, are discussed. PMID- 8010196 TI - Symptomatic interleukin-2-induced cholecystopathy in patients with HIV infection. AB - OBJECTIVE: This study reports the clinical and radiologic findings in seven patients infected with HIV who had 10 consecutive episodes of symptomatic cholecystopathy induced by infusion of interleukin-2. SUBJECTS AND METHODS: Ten episodes of right upper quadrant pain associated with gallbladder wall thickening were seen in seven of 29 HIV-infected patients who received IV interleukin-2. Patients received 6-18 million IU/day of continuous interleukin-2 infusion for 5 days. Patients with right upper quadrant pain underwent sonographic examinations, which were interpreted prospectively. Medical records and previous sonographic studies were reviewed retrospectively. Follow-up was obtained through outpatient visits and sonography. RESULTS: Right upper quadrant pain during these 10 episodes of cholecystopathy usually developed 4-5 days after starting infusion of interleukin-2. Sonography during that time showed gallbladder wall thickening (mean thickness, 12.4 mm; range, 5-18 mm) and a wide variety of sonographic appearances. Tenderness during sonography was focal in six episodes, diffuse in one, and absent in three. Sludge was identified in one episode; calculi were not seen. Findings on radionuclide biliary scans were normal in three cases. Symptoms abated rapidly in every case after infusion of interleukin-2 was reduced or stopped. No surgery was necessary. When treatment was repeated, three patients had recurrent episodes, with clinical courses and sonographic aberrations showing little variance from the initial episodes. Follow-up sonography in three episodes showed a maximal thickness of the gallbladder wall of 4 mm. No patient had a history or laboratory evidence of intrinsic biliary disease. CONCLUSION: Symptomatic thickening of the gallbladder wall during infusion of interleukin-2 can exactly mimic other forms of acalculous cholecystitis, except that when associated with interleukin-2 the thickening is rapidly reversible and surgery is not required. Radionuclide scans can be useful in clinical decision making. The process appears to be benign, and cessation of interleukin-2 therapy, along with close clinical observation, appears to be the appropriate treatment. PMID- 8010198 TI - Diagnosis of pelvic endometriosis: fat-suppressed T1-weighted vs conventional MR images. AB - OBJECTIVE: The purpose of this study was to compare fat-suppressed T1-weighted with conventional MR images for the diagnosis of endometriosis, focusing on the detectability of peritoneal implants, and to evaluate the usefulness of MR imaging in predicting the severity of disease. SUBJECTS AND METHODS: We analyzed the MR images of 31 patients with clinically suspected endometriosis. Laparoscopy confirmed no evidence of disease in two and endometriosis in 29. Conventional T1- and T2-weighted images and supplementary axial fat-suppressed images were obtained in all patients. In both groups, detection of endometriotic lesions with MR imaging was compared with detection at laparoscopy. Only the findings on fat suppressed images were used to evaluate the usefulness of MR imaging in predicting the severity of disease. Early stages of disease included stages I and II; advanced stages of disease included stages III and IV. RESULTS: Diagnostic accuracy was higher with fat-suppressed imaging (77%) than with conventional imaging (55%) (p = .06). The overall sensitivity in detecting peritoneal implants was significantly higher with fat-suppressed imaging (61%) than with conventional imaging (27%) (p < .01). The disease was likely to be at an early stage when MR images showed peritoneal implants that were 5 mm or less in maximum diameter. The disease was likely to be at an advanced stage when MR images showed an endometrial cyst that was larger than 1.5 cm. CONCLUSION: Our results show that fat-suppressed MR imaging is more accurate in the diagnosis of pelvic endometriosis and is better for predicting the severity of disease than conventional MR imaging is. PMID- 8010197 TI - Partial splenic embolization for the treatment of chronic idiopathic thrombocytopenic purpura. AB - OBJECTIVE: The purpose of this study was to assess the effectiveness of partial splenic embolization in the treatment of chronic idiopathic thrombocytopenic purpura. SUBJECTS AND METHODS: Twenty-six patients with chronic idiopathic thrombocytopenic purpura underwent partial splenic embolization and were followed up for 6-61 months. The condition was refractory to steroids in 20 of 26 patients. The other six patients, in whom a response to steroids was shown, could not be withdrawn from steroid therapy because their platelet counts decreased with any decrease in steroid dose. Five of 26 patients underwent splenectomy after partial splenic embolization, and the other patients were followed up without medical treatment until platelet counts decreased below 3 x 10(10)/l. The therapeutic effect of partial splenic embolization was defined on the basis of the platelet count at the last follow-up after partial splenic embolization: complete response, greater than 10 x 10(10)/l; partial response, 5 x 10(10)/l to 10 x 10(10)/l; and no response, less than 5 x 10(10)/l without medication. RESULTS: Partial splenic embolization brought a complete response in seven (33%) of 21 patients, a partial response in eight (38%), and no response in six (29%). In four of five patients, who later underwent splenectomy, response to partial splenic embolization was coincident with the response to splenectomy. No serious complications occurred, but minor complications such as abdominal pain, fever, and nausea were observed in most patients. CONCLUSION: This study suggests that partial splenic embolization might be useful as an alternative to splenectomy in the treatment of chronic idiopathic thrombocytopenic purpura. PMID- 8010199 TI - Clinical value of bone densitometry. AB - The purpose of this article is to provide insight into the long-standing controversy over the clinical value of noninvasive measurement of bone mass. Results of recent studies have increasingly supported the judicious use of bone densitometry as a clinical tool [1]. These reports contradict editorials on the limitations of bone densitometry that have appeared in a variety of subspecialty publications [2,3]. The importance of bone mass measurement is underscored by the lack of success in predicting bone density from various combinations of anthropometric and historical variables. Growing evidence suggests that densitometry is a useful tool for determining which women near menopause are at risk for osteoporosis and, therefore, are candidates for estrogen-replacement therapy. This article summarizes current concepts on the subject and attempts to prove that bone densitometry is a beneficial and indicated procedure for selected patients. PMID- 8010200 TI - Coding and reimbursement issues for dual-energy X-ray absorptiometry. AB - Bone densitometry has a unique and invaluable place in the prevention, diagnosis, and management of osteoporosis. Dual-energy X-ray absorptiometry (DEXA) is currently considered the bone densitometric technique of choice. With this method, the patient at risk for osteoporosis can be identified so that appropriate clinical interventions to prevent fracture can be undertaken. DEXA also allows assessment of the efficacy of these interventions in preventing bone loss. As with any other technology, however, bone densitometry must be properly used in the clinical setting to achieve this benefit. Critical to the proper use of the technology is the realization that a complete assessment of fracture risk requires the measurement of both the spine and the proximal part of the femur, not either site alone, and that assessment of therapeutic efficacy might also require the measurement of both sites, not either site alone. Effective January 1, 1994, the Clinical Procedural Terminology (CPT) code for DEXA has been 76075. This code is intended for measurement of a single site and is to be reimbursed at a global rate of $60.85. Although the assignment of a CPT code for this clinically valuable technology is most welcome, the lack of a code reflecting at least two sites of study and the low rate of reimbursement for a single site suggest a misunderstanding of the actual costs of the technology and the need, on occasion, for measurements at multiple sites. PMID- 8010201 TI - Evaluation of tibial plateau fractures: efficacy of MR imaging compared with CT. AB - OBJECTIVE: CT is often used after plain films to evaluate fractures of the tibial plateau. Because MR imaging can show associated soft-tissue injuries as well as fractures, we hypothesize that MR is superior to CT for imaging these injuries. Accordingly, we compared the efficacy of MR imaging and CT in 22 patients with tibial plateau fractures. SUBJECTS AND METHODS: CT with two-dimensional reconstruction and MR examinations were performed in 22 patients with tibial plateau fractures. The images were interpreted by four radiologists and two orthopedic surgeons. Findings on CT scans and plain films were used to determine the configuration of the fractures and to classify them according to the Schatzker system. This was done with findings on MR images and plain films at a separate session. The MR images were also evaluated for ligamentous and meniscal injuries. A qualitative side-by-side comparison of two-dimensional CT scans and MR images for depiction of fracture configuration was done. Imaging results were correlated with observations from physical examinations in all patients and with surgical findings in 12 patients. RESULTS: All of the six types of fractures of the Schatzker classification were observed in this series. Comparison of two dimensional CT reconstructions and MR images for depiction of fracture configuration revealed that the two techniques were equal in 14 patients, MR imaging was superior to CT in five patients, and CT was superior to MR imaging in three patients (who had very complex and comminuted fractures). In addition, MR imaging showed 12 complete ligamentous tears and 15 partial ligamentous tears in 15 (68%) of the 22 patients. MR showed meniscal injuries in 12 (55%) of the 22 patients. CONCLUSION: MR imaging was equivalent or superior to two-dimensional CT reconstruction for depiction of fracture configuration in most patients. In addition, MR showed significant soft-tissue injuries. We believe that MR imaging is the preferable imaging technique for most patients with fractures of the tibial plateau. PMID- 8010202 TI - "Magic-angle" phenomenon: a cause of increased signal in the normal lateral meniscus on short-TE MR images of the knee. AB - OBJECTIVE: Increased signal intensity is frequently present in the upsloping, medial segment of the posterior horn of the normal lateral meniscus on routine short-TE MR images of the knee. This attribute can mimic or obscure abnormalities in this portion of the meniscus. In the present study, we examined whether this appearance could be accounted for by the "magic-angle" phenomenon resulting from the angular orientation of this meniscal segment relative to the static magnetic field. SUBJECTS AND METHODS: Fifty-eight consecutive knee MR examinations were studied. Sixteen were excluded because of frank evidence of preexisting abnormality of the lateral meniscus. In the remaining 42 examinations, the signal intensity in the medial segment of the posterior horn of the lateral meniscus on short-TE (< 20 msec) sequences was correlated with the angular alignment of this meniscal segment relative to the static magnetic field. In five asymptomatic volunteers, meniscal signal intensities were monitored as the leg was positioned in various degrees of abduction. RESULTS: Increased signal was present in the medial segment of the posterior horn of the lateral meniscus in 31 (74%) of the 42 patients. In 25 (81%) of these, this meniscal segment was oriented at 55-60 degrees. Increased signal intensity was also present in this meniscal segment in three (60%) of five asymptomatic knees imaged in the neutral position. In each of these, abduction of the leg decreased the meniscal signal by 52-80%. Pathologic evaluation of two menisci showed numerous concentrically arranged collagen fibers. CONCLUSION: Increased signal in the upsloping portion of the posterior horn of the lateral meniscus on short-TE images often is due to the magic-angle phenomenon rather than to meniscal degeneration or tear. PMID- 8010203 TI - Cystic lesions around the knee joint: MR imaging findings. AB - A wide variety of cystic lesions may be encountered in the soft tissues and bones during routine MR imaging of the knee. These lesions represent encapsulated fluid collections and exhibit low signal intensity on T1-weighted images and high signal intensity on T2-weighted images because of their high content of free water. Many lesions produce clinical features suggestive of internal derangement of the knee, so correct MR diagnosis is needed to avoid unnecessary arthroscopy and to guide specific therapy. The purpose of this essay is to illustrate the MR appearance of cystic lesions that can be found around the knee and to explain the clinical features and significance of these lesions. PMID- 8010204 TI - Lipoma arborescens of the knee: MR demonstration. PMID- 8010205 TI - Sedation of difficult-to-sedate children undergoing MR imaging: value of thioridazine as an adjunct to chloral hydrate. AB - OBJECTIVE: The purpose of this prospective study was to evaluate the safety and efficacy of thioridazine as an adjunct to chloral hydrate sedation when children undergoing MR imaging are difficult to sedate. SUBJECTS AND METHODS: All 87 children in the study either could not be sedated with chloral hydrate alone or were mentally retarded. Thioridazine (2-4 mg/kg) was administered orally 2 hr before and chloral hydrate (50-100 mg/kg) was administered orally 30 min before the 104 MR examinations. All children were monitored by continuous pulse oximetry. All images were individually evaluated by pediatric radiologists and were graded acceptable if they contained only minimal motion artifact or no motion artifact. Studies were considered successful only when 95% or more of the images were acceptable. RESULTS: MR imaging was successful in 93 (89%) of 104 examinations. The success rate for children entered into the study because of prior failure of chloral hydrate sedation was not significantly different from the success rate for children with mental retardation. A tendency for increasing failure rate with age was not significant. No serious complications occurred during the study. The most common adverse reaction, transient reduced oxygen saturation, was seen in five children. Other adverse effects encountered were vomiting in four children, hyperactivity in two children, transient tachycardia in one child, and prolonged sedation in one child. No child required hospitalization because of an adverse reaction to sedation. CONCLUSION: The study indicates that thioridazine is a safe and effective adjunct to chloral hydrate when a child undergoing MR imaging is difficult to sedate. PMID- 8010206 TI - Bronchopulmonary dysplasia: value of CT in identifying pulmonary sequelae. AB - OBJECTIVE: Pulmonary dysfunction is common in children who survive bronchopulmonary dysplasia. Chest radiographs are not satisfactory for the identification of the sequelae of bronchopulmonary dysplasia because, although they often show abnormalities, the abnormalities are usually minor and sometimes absent. We therefore assessed the value of CT for identifying the sequelae of bronchopulmonary dysplasia. MATERIALS AND METHODS: Twenty-three children (mean age, 4 years) who had survived neonatal bronchopulmonary dysplasia and had signs of chronic pulmonary dysfunction (recurrent episodes of coughing, wheezing, dyspnea, pneumonia, respiratory insufficiency) were examined with chest radiographs and high-resolution CT scans of the chest. Two reviewers qualitatively analyzed the chest radiographic and CT findings by describing the most consistently found lesions and their frequencies. RESULTS: The chest radiographs showed hyperexpansion in 17, hyperlucent areas in 11, and linear opacities in 10 of the 23 children. Pleural thickening was not observed, and four children had normal findings on chest radiographs. All 23 CT scans showed abnormalities, including multifocal areas of hyperaeration, well-defined linear opacities, and triangular subpleural opacities with an external base and an internal apex. In 20 of 23 children, all three abnormalities were present. For the three other children, two of these three abnormalities were found. No bronchiectasis was observed in any of the cases. CONCLUSION: Lesions in survivors of bronchopulmonary dysplasia with chronic pulmonary dysfunction are visualized better on CT scans than on chest radiographs. Importantly, CT findings of multifocal areas of hyperaeration, numerous linear opacities facing triangular subpleural opacities visible on several consecutive sections, and no bronchiectasis should suggest the presence of sequelae of bronchopulmonary dysplasia. PMID- 8010207 TI - CT of abdominal aortic aneurysms. AB - CT often plays an important role in the evaluation of abdominal aortic aneurysms. Many vascular surgeons consider it an integral part of the preoperative assessment of aneurysms. CT is also used to examine symptomatic patients with possible aneurysmal ruptures when the diagnosis is unclear and to study patients with aortic grafts in whom potentially lethal complications, such as graft infection, aortoenteric fistulas, and anastomotic pseudoaneurysms, are clinically suspected. This paper reviews the current role of CT in the assessment of patients with abdominal aortic aneurysms. PMID- 8010208 TI - MR imaging of head and neck tumors: comparison of T1-weighted contrast-enhanced fat-suppressed images with conventional T2-weighted and fast spin-echo T2 weighted images. AB - OBJECTIVE: The purpose of this study was to determine the value of three MR pulse sequences for the detection of tumors and abnormal lymph nodes in the head and neck. This was accomplished by quantifying differences in contrast between tumor, lymph node, and respective adjacent tissue on contrast-enhanced fat-suppressed T1 weighted MR images, conventional spin-echo T2-weighted images, and fast spin-echo fat-suppressed T2-weighted images in a group of patients with head and neck tumors. SUBJECTS AND METHODS: Two groups of patients with head and neck tumors were studied. In the first group (16 patients), contrast-enhanced fat-suppressed T1-weighted images were compared with conventional spin-echo T2-weighted images. In the second group (21 patients), contrast-enhanced fat-suppressed T1-weighted images were compared with fast spin-echo fat-suppressed T2-weighted images. The detectability of tumor and abnormal lymph nodes was measured by calculating the contrast-to-noise ratio. RESULTS: The fat-suppressed T1-weighted images had significantly higher (p < or = .02) contrast-to-noise ratios for both the primary tumor and lymph nodes than either conventional or fast spin-echo T2-weighted images did. However, subjective evaluation of the contrast-to-noise ratios proved satisfactory for tumor detection with all three imaging sequences (contrast enhanced fat-suppressed T1-weighted, fast spin-echo fat-suppressed T2-weighted, and conventional T2-weighted). CONCLUSION: Our results show that fat-suppressed contrast-enhanced T1-weighted images provide the highest contrast-to-noise ratio for head and neck tumors and abnormal lymph nodes. However, head and neck tumors encompass a broad range of neoplasms that are distributed in a complicated anatomic area. Therefore, in some patients, a combination of contrast-enhanced fat-suppressed T1- and T2-weighted images, preferably fast spin-echo fat suppressed images, is useful for detection of these tumors and nodal metastases. PMID- 8010209 TI - Tuberculosis manifested by a laryngeal mass on CT scans. PMID- 8010210 TI - Vascularity of meningiomas and neuromas: assessment with dynamic susceptibility contrast MR imaging. AB - OBJECTIVE: Dynamic susceptibility-contrast MR imaging provides hemodynamic information about normal and pathologic tissue of the brain. The purpose of this study was to determine the value of this technique in assessing the vascularity of meningiomas and neuromas. MATERIALS AND METHODS: Sixteen patients with extraaxial brain tumors (eight meningiomas and eight neuromas) and seven subjects without evident brain lesions were studied with a conventional 1.5-T MR unit. Dynamic susceptibility-contrast MR imaging was done with a gradient-echo technique (33/23/10 degrees [TR/TE/flip angle]) during bolus IV injection of 0.15 mmol/kg gadopentetate dimeglumine. The integral of the rate of change in T2* (integral of delta R2*dt) was calculated and compared among the brain tumors and normal brain. RESULTS: The mean integral of delta R2*dt value obtained was significantly higher in meningiomas than in neuromas (p < .001), which shows that meningiomas are generally more vascular than neuromas. We found no significant difference in the mean integral of delta R2*dt between neuromas and normal brain regions. CONCLUSION: Dynamic susceptibility-contrast MR imaging provides information about the degree of the vascularity of meningiomas and neuromas that is not available with conventional MR imaging. PMID- 8010211 TI - Friedreich's ataxia: MR findings involving the cervical portion of the spinal cord. AB - OBJECTIVE: Loss of myelinated fibers and gliosis in the posterior and lateral columns of the spinal cord are histopathologic hallmarks of Friedreich's ataxia. These are accompanied by atrophy of the upper portion of the spinal cord. We performed a study to determine if MR imaging can be used to detect signal changes in the white matter tracts of the cervical spinal cord in these patients. SUBJECTS AND METHODS: The cervical spinal cord was imaged with a 0.5-T MR imaging system in 10 patients with Friedreich's ataxia and in 14 patients with cerebellar ataxias, who served as control subjects. In all of them, the examination protocol included sagittal T1-weighted spin-echo images, sagittal short T1 inversion recovery images, and axial cardiac-gated long TR spin-echo or ungated low-flip angle (20 degrees) gradient-recalled-echo images from C2 to C6. The anteroposterior diameter of the spinal cord at the level of C3 on axial images was measured on the display console in patients and control subjects. Two observers who did not know the clinical diagnosis were then asked to evaluate hard copies of the entire image set for each subject for possible intramedullary signal abnormalities. RESULTS: The anteroposterior diameter of the spinal cord was decreased in all but one of the patients with Friedreich's ataxia. Abnormal signal in the posterior or lateral columns of the spinal cord was observed on sagittal and axial images in nine patients with Friedreich's ataxia and in none of the control subjects. CONCLUSION: MR images of the cervical spinal cord in patients with Friedreich's ataxia show thinning and intramedullary signal changes in the cervical portion of the spinal cord, consistent with degeneration of posterior and lateral white matter tracts. These MR findings might be helpful for differential diagnosis in patients with progressive ataxia of uncertain clinical type. PMID- 8010212 TI - Occipital condyle fracture: significance in the assessment of occipitoatlantal stability. PMID- 8010213 TI - CT-guided core biopsy of difficult lesions: a modified coaxial approach. PMID- 8010214 TI - MR angiography of normal pelvic arteries: comparison of signal intensity and contrast-to-noise ratio for three different inflow techniques. AB - OBJECTIVE: Two-dimensional (2D) time-of-flight (TOF) MR angiography has been the standard technique for evaluating arteries of the lower extremity. However, this technique is limited by artifacts resulting from vessel pulsation, as well as by relatively poor vessel-to-background contrast. The purpose of this study was to evaluate two cardiac-gated inflow techniques to determine whether they exhibited better contrast and signal performance than the standard technique of 2D TOF MR angiography of the iliac arteries. SUBJECTS AND METHODS: Fourteen subjects who had no clinical evidence of vascular disease had standard 2D TOF, gated 2D TOF, and gated 2D turbo field-echo MR angiography. Images were evaluated for signal intensity ratio, signal-to-noise ratio, and contrast-to-noise ratio, in addition to qualitative evaluation. RESULTS: Turbo field-echo MR angiography exhibited significantly higher signal-intensity, signal-to-noise, and contrast-to-noise ratios than did either gated or standard MR angiography for all vessel segments. We found no significant difference between gated and standard 2D TOF techniques for any vessel segment. Qualitative features of turbo field-echo MR angiography included improved visualization of horizontal vessel segments compared with the standard 2D TOF technique, less effective venous saturation compared with either the gated or standard 2D TOF technique, and increased ghosting artifacts compared with the gated 2D TOF technique. CONCLUSION: Two-dimensional turbo field-echo MR angiography exhibits improved signal and contrast for evaluation of normal iliac segments compared with standard or gated 2D TOF MR angiography. This technique should replace standard 2D TOF MR angiography for evaluation of the iliac arteries. PMID- 8010215 TI - MR imaging (including MR angiography) of abdominal aortic aneurysms: comparison with conventional angiography. AB - OBJECTIVE: The purpose of this report is to compare the results of MR imaging, including MR angiography, with the results of conventional angiography in the imaging of abdominal aortic aneurysms (AAA). SUBJECTS AND METHODS: Twenty seven nonconsecutive patients with known AAA underwent both MR imaging (including MR angiography) and conventional angiography preoperatively. MR imaging was done before angiography according to the following protocol in all patients: sagittal and coronal T1-weighted images of the abdomen, followed by axial MR angiograms obtained with a multiple overlapping thin-slab acquisition (MOTSA) three dimensional time-of-flight (3D TOF) volume centered on the renal arteries. Last, coronal MR angiograms were obtained with a dynamic contrast-enhanced 3D TOF volume centered on the aorta. Conventional angiography was subsequently performed in all patients. Data from each study were collected prospectively and analyzed in a blinded manner. For the MR studies, all sequences were used to determine the extent of the AAA and the presence of iliac aneurysms; stenotic disease of the celiac, superior mesenteric, renal, and iliac arteries and the number and location of renal arteries were determined from the MR angiograms. For evaluation of the extent of the aneurysm, results from both techniques were compared with surgical results; otherwise MR angiography was compared with conventional angiography. Confidence intervals for sensitivity and specificity were calculated at the 95% level. The McNemar test was used for comparison of proportions. RESULTS: MR angiography had a sensitivity of 100% (4/4) and a specificity of 91% (21/23) for the four stenoses of the celiac artery that were greater than 50%. For detection of renal artery stenoses of greater than 50%, present in nine arteries, the sensitivity was 89% (8/9) and specificity was 98% (49/50). MR angiography showed 100% (54/54) of all main renal arteries and 78% (7/9) of all accessory renal arteries seen on conventional angiograms. The proximal extent of the aneurysm was correctly predicted on the basis of MR findings in 100% (26/26) of patients with surgical correlation, compared with 92% (24/26) when conventional angiograms were used. This difference was not statistically significant (p > .1). MR imaging had a sensitivity of 100% (19/19) for detection of isolated aneurysms of the common iliac artery, and MR angiography had a 100% sensitivity (5/5) and specificity (103/103) for detection of stenosis greater than 50% in the common and external iliac arteries. One circumaortic left renal vein was visualized on MR images. CONCLUSION: These results suggest that MR angiography may be a useful noninvasive method for determining the presence of coexistent celiac, superior mesenteric, renal, and iliac atherosclerotic disease in patients with AAA. PMID- 8010216 TI - Interactive atlas of joint anatomy on MR images. AB - We designed and developed an atlas of joint anatomy based on MR images. Using a workstation that consisted of a computer and a videodisc player, each with its own monitor, the program presented complete sets of labeled MR images of the joints by using a variety of common pulse sequences in standard imaging planes. The images were stored on videodisc and were retrieved and displayed under the control of the computer program. The images could be viewed in a self-paced, structured sequence or in any arbitrary, self-directed way. Interactive features included a quiz mode that challenged the user to name the anatomic structures, one at a time. The atlas has been exhibited at national meetings and currently is used in our residency and fellowship training programs. PMID- 8010217 TI - What is the significance of numerous small (1-2 mm) radiolucent nodules in the jejunum seen on barium studies? PMID- 8010218 TI - When is a Schatzki ring clinically significant, and what is the best maneuver to demonstrate it on barium swallow? Does the abnormality progress if it is not treated? PMID- 8010219 TI - What is the significance of the incidental discovery of a unilocular ovarian cyst in a postmenopausal woman (either with or without a family history of ovarian cancer) during a pelvic sonographic examination to exclude ovarian carcinoma? PMID- 8010220 TI - How does one deal with a renal cyst that appears to be Bosniak class II on a CT scan but that has sonographic features suggestive of malignancy (e.g., nodularity of wall or a nodular, irregular septum)? PMID- 8010221 TI - What is the radiologist's current role in the diagnosis and treatment of sexual impotence in men? PMID- 8010222 TI - What is the minimum number of plain radiographs necessary to evaluate the cervical spine in patients who have had trauma? PMID- 8010223 TI - What is the significance of the "vertebral vacuum phenomenon"? PMID- 8010224 TI - What are the relative roles of Doppler sonography and femoral arteriography in the diagnostic evaluation of patients with ischemic changes in the foot? Should sonography be performed first or is it appropriate to proceed directly to arteriography? What is the value of sonography in this circumstance? PMID- 8010225 TI - CT detection of small pneumothorax. PMID- 8010226 TI - Cellulose granulomatosis of the lungs: CT findings. PMID- 8010227 TI - Nodulocystic acne as the cause of "ring lesions" on mammograms. PMID- 8010228 TI - Inadvertent intracranial placement of a nasogastric tube. PMID- 8010229 TI - Videofluoroscopic evaluation of swallowing. PMID- 8010230 TI - Importance of differential air-fluid levels on plain radiographs in the diagnosis of bowel obstruction. PMID- 8010231 TI - Splenic hematoma causing colonic obstruction. PMID- 8010232 TI - Diagnosis of colonic obstruction based on findings on plain radiographs. PMID- 8010233 TI - Evaluation of patency of a ureteral stent: value of color Doppler imaging. PMID- 8010234 TI - Sonographic features of a dysplastic kidney in Melnick-Fraser syndrome. PMID- 8010235 TI - Bilateral thalamic venous infarctions mimicking tumor. PMID- 8010236 TI - Pituitary apoplexy associated with dural (tail) enhancement. PMID- 8010237 TI - Intracallosal cyst: MR demonstration. PMID- 8010238 TI - Wilson's disease: contrast enhancement of cerebral lesions on MR images after penicillamine therapy. PMID- 8010239 TI - Intrathyroidal branchial cleft cyst in Hashimoto's thyroiditis. PMID- 8010240 TI - Embolization of the iliac artery by a bullet. PMID- 8010241 TI - Volumetric high-resolution CT in the diagnosis of interstitial lung disease and bronchiectasis: diagnostic accuracy and radiation dose. AB - OBJECTIVE: The purpose of this study was to evaluate the diagnostic accuracy and radiation dose of volumetric high-resolution CT in the diagnosis of interstitial lung disease and bronchiectasis when four contiguous sections were acquired at each of three levels. The potential benefits were weighed against the increased radiation dose of multiple scans. SUBJECTS AND METHODS: High-resolution CT scans of four contiguous sections were obtained at each of three locations (the aortic arch, the carina, and 2 cm above the diaphragm) in 50 consecutive patients (mean age, 44 years old) with known or suspected interstitial lung disease or bronchiectasis who were referred for evaluation with high-resolution CT. Each individual scan was analyzed for the presence of motion-induced streaking, blurring, or doubling. The diagnostic information contained in each set of four scans was compared with that contained in the first of the four scans in the set. RESULTS: Motion degraded at least one of the four images in each set in 69 (46%) of 150 volumetric acquisitions. When the full set of four images was considered instead of just the first scan from the set, the number of motion-free studies in patients with suboptimal respiratory suspension was increased by 40% (from 99 to 139). Diagnostic accuracy was improved as more features were identified on contiguous scans: the sensitivity of the first scan compared with that of the complete set of four scans was 84% for the detection of bronchiectasis, 97% for ground-glass opacity, 88% for honeycombing, 88% for septal thickening, and 86% for nodular opacities. Although the integral radiation exposure for a set of four CT scans was 2.8 times that of a single scan obtained with standard technique, peak skin exposure was unchanged. Slightly increased image noise with the reduced technique compromised diagnostic ability in 6% of studies. CONCLUSION: The use of volumetric high-resolution CT increased diagnostic accuracy, particularly for bronchiectasis at the lung bases, without increasing peak skin radiation exposure. With the availability of four contiguous scans per anatomic level, the subjective confidence in interpretation and number of motion-free studies also increased. PMID- 8010242 TI - Small-airway diseases of the lungs: findings at expiratory CT. AB - CT performed in patients during suspended full expiration has recently been used to reveal a major physiologic consequence of airway diseases, particularly diseases of those smaller airways beyond the segmental branches: air trapping. Lung regions that retain air during exhalation (air trapping) remain more lucent than normal lung regions do. Detection of air trapping can provide clues to an otherwise unsuspected or underappreciated small-airway disease. PMID- 8010243 TI - Combined lobar atelectasis of the right lung: imaging findings. AB - Combined lobar atelectasis refers to the condition in which the volumes of two lobes of the lung are decreased simultaneously. Because the right lung has three lobes, three combinations of combined atelectasis are possible. The most frequent combination is that of middle and lower lobar atelectasis caused by obstruction of the bronchus intermedius [1,2]. Combined atelectasis of the upper and middle lobes is uncommon, although it occurs more frequently than anticipated [1]. The least common combination is that of right upper and lower lobe atelectasis. Awareness of the radiographic and CT findings of combined lobar atelectasis of the right lung is important in making the correct diagnosis. In this pictorial essay, we illustrate the spectrum of radiographic and CT features of this condition. PMID- 8010244 TI - Medicine in American art. Just born. PMID- 8010245 TI - Endobronchial hamartoma: CT findings in three patients. PMID- 8010246 TI - Cost-effectiveness of unenhanced MR imaging vs contrast-enhanced CT of the abdomen or pelvis. AB - OBJECTIVE: The purpose of this study was to compare the cost of unenhanced MR imaging with that of CT with high- or low-osmolality contrast agents for abdominal or pelvic imaging in patients at risk for nephrotoxic effects induced by contrast material. MATERIALS AND METHODS: Using decision analysis, we evaluated direct medical care costs associated with the use of CT with high- or low-osmolality contrast agents vs MR imaging. We used data from a variety of sources and assumed that the three imaging techniques provide nearly equivalent diagnostic information. The base-case analysis assumed that patients were at low risk (i.e., 2%) for development of nephrotoxic effects. Nephrotoxic effects were defined as increases in the serum level of creatinine of 50% or more above baseline. Our analysis took the perspective of the hospital and used estimated hospital costs, not charges. Sensitivity analyses were performed on risk estimates for development of nephrotoxic effects and for the estimates of medical care costs. RESULTS: For the base case, CT with a high-osmolality contrast agent is the least costly imaging strategy. When the risk of nephrotoxic effects exceeds 5% for high-osmolality contrast agents or 2.6% for low-osmolality contrast agents, then MR imaging is the preferred strategy. The model is relatively insensitive to treatment costs. CONCLUSION: From a hospital's perspective, MR imaging of the abdomen or pelvis is cost minimizing in patients at high risk for nephrotoxic effects induced by contrast agents. Use of low osmolality contrast agents must reduce the frequency of nephrotoxic effects in high-risk patients by at least 50% to be less costly than MR imaging. PMID- 8010247 TI - MR detection of leakage from silicone breast implants: value of a silicone selective pulse sequence. AB - OBJECTIVE: The purpose of this study was to determine the value of MR imaging with a silicone-selective pulse sequence for detecting leakage from silicone breast implants. SUBJECTS AND METHODS: Women with silicone breast implants were referred for this study on the basis of clinical or imaging findings suggestive of implant rupture. Twenty-eight patients with 38 implants were examined with silicone-selective MR imaging and also underwent surgical removal of the studied implant. All but four also had mammography before MR imaging. Results of silicone selective MR imaging for the detection of silicone leakage were compared with mammographic and surgical findings. Surgical proof was considered the gold standard. RESULTS: Silicone-selective MR imaging showed an apparently intact implant in 21 cases; 20 of these were found to be intact at surgery. Silicone selective MR imaging showed evidence of leakage in 17 implants, all of which showed leakage at surgery. The sensitivity for detection of leakage was 94%; the specificity was 100%. The findings of silicone-selective MR imaging and mammography were in agreement in 30 of 34 cases in which both studies were performed. In the four cases of disagreement, surgical findings agreed with MR findings in three and with mammographic findings in one. When the findings of mammography and silicone-selective MR imaging were combined, the correct status (leakage or no leakage) of all implants examined was determinable. CONCLUSION: Silicone-selective MR imaging is highly effective for detecting leakage from silicone breast implants. Accuracy is improved when mammographic and MR findings are considered together. PMID- 8010248 TI - Diagnosis of breast implant rupture: imaging findings and relative efficacies of imaging techniques. AB - OBJECTIVE: The purpose of this study was to compare the efficacies of mammography, sonography, CT, and MR imaging in the detection of breast implant rupture and to analyze the imaging findings. SUBJECTS AND METHODS: Thirty-two women with 63 silicone breast implants participated in the study. All but one had signs and symptoms suggestive of rupture, and all had requested that their implants be removed before they were enrolled in this imaging study. All patients had film-screen mammography, sonography, CT, and MR imaging. Twenty-two ruptures were found at surgery; 21 were intracapsular and one was extracapsular. The relative efficacies of the imaging studies were determined, and the imaging findings were compared with the surgical results. RESULTS: Of the 32 women with 63 implants, mammographic sensitivity for detecting implant rupture was only 23% but the specificity was 98%. Sonography had a higher sensitivity (59%), but its specificity was significantly lower (79%). CT had a sensitivity of 82% and a specificity of 88%. MR was the only imaging technique that consistently provided evidence that enabled the evaluation of intracapsular and extracapsular ruptures. The sensitivity and specificity of MR imaging were 95% and 93%, respectively. CONCLUSION: Our results show that MR imaging is more sensitive and specific for the detection of breast implant rupture than is mammography, CT, or sonography. PMID- 8010249 TI - Hemangiopericytoma of the breast: mammographic and sonographic findings. PMID- 8010250 TI - Barium studies in patients with Barrett's esophagus: importance of focal areas of esophageal deformity. AB - OBJECTIVE: I report a subtle finding of columnar metaplasia of the esophagus (Barrett's esophagus) on barium examination that to my knowledge has not been described before. The finding is a focal mural deformity associated with fixed transverse folds and minimal limitation of distensibility of the esophagus at least 4 cm proximal to the esophagogastric junction. MATERIALS AND METHODS: The abnormality was seen in four patients who had air-contrast upper gastrointestinal barium studies for evaluation of various gastrointestinal symptoms. Only one had symptoms referable to the esophagus. A diagnosis of Barrett's esophagus was suggested on the basis of the findings on barium studies and was confirmed by endoscopic biopsy. RESULTS: Initial radiographs showed subtle contour defects in the esophageal wall at least 4 cm proximal to the esophagogastric junction in each patient. These appeared as focal indentations (two cases) or a gradual concavity (two cases) in the wall that could be mistaken for a normal extrinsic impression or normal variation. Radiographs obtained with increased distension or in different degrees of obliquity showed fixed transverse folds suggestive of submucosal fibrosis. Barrett's esophagus was observed at endoscopy, but no endoscopic findings correlated with the focal changes seen on radiographs. CONCLUSION: Identification of focal defects in the esophageal contour at least 4 cm proximal to the esophagogastric junction on barium studies raises the possibility of Barrett's esophagus. The diagnosis is further suggested if repeat radiographs obtained with increased distension and different degrees of obliquity show fixed transverse folds, limited distensibility of the esophageal wall, or both. PMID- 8010252 TI - Exophytic adenocarcinoma of the stomach: CT findings. AB - OBJECTIVE: Exophytic adenocarcinomas of the stomach are tumors that have large extraluminal portions. Exophytic growth of gastric carcinoma is rare, and such tumor may be confused with gastric leiomyosarcoma. The purpose of this study was to assess the CT findings of exophytic adenocarcinoma of the stomach and to determine their value in distinguishing between it and gastric leiomyosarcoma. MATERIALS AND METHODS: Twenty patients with exophytic adenocarcinomas of the stomach confirmed by surgery or endoscopic biopsy were included in the study. CT scans were assessed retrospectively for the size, location, and character of the mass and the presence of adjacent thickening of the gastric wall and outlet obstruction. RESULTS: The masses were from 5 to 14 cm in diameter (mean, 9 cm). The mass was in the gastric antrum in 11 cases, the body of the stomach in six cases, the body and antrum in two cases, and the gastric fundus and body in one case. CT showed an exogastric mass with a variable degree of internal low density or necrosis in all 20 cases. Thickening of the gastric wall adjacent to the mass appeared to be a specific finding of exogastric adenocarcinoma (n = 14); it was not seen in reported cases of leiomyosarcoma. Gastric outlet obstruction was seen in four cases, and ulcer was detected in eight cases. The degree of low density or necrosis within the mass was minimal in eight cases, moderate in seven cases, and severe in five cases. CONCLUSION: Our results suggest that CT findings of thickening of the gastric wall adjacent to an exogastric mass, representing spread of cancer to adjacent gastric wall, and/or gastric outlet obstruction are typical of exophytic adenocarcinoma of the stomach and allow distinction between it and gastric leiomyosarcoma. PMID- 8010253 TI - Differentiating sigmoid diverticulitis from carcinoma on CT scans: mesenteric inflammation suggests diverticulitis. AB - OBJECTIVE: The purpose of this study was to analyze the usefulness of two specific CT signs of sigmoid mesenteric inflammation (fluid at the root of the mesentery and vascular engorgement) for identifying and differentiating sigmoid diverticulitis from carcinoma. MATERIALS AND METHODS: CT scans of 69 patients with surgically proved sigmoid diverticulitis were retrospectively reviewed and compared with CT findings in 29 patients with surgically proved sigmoid carcinoma. Two specific patterns of inflammation of the sigmoid mesentery were analyzed: fluid at the root of the sigmoid mesentery and engorgement of the sigmoid mesenteric vessels. RESULTS: The CT findings were present more often in patients with sigmoid diverticulitis than in those with carcinoma (p < .001). Fluid at the base of the mesentery had a sensitivity, specificity, and positive predictive value for diverticulitis of 36%, 90%, and 89% respectively. Vascular engorgement alone had a sensitivity, specificity, and positive predictive value of 29%, 100%, and 100%, respectively. CONCLUSION: Our results suggest that CT findings of fluid at the root of the mesentery and vascular engorgement are useful in distinguishing sigmoid diverticulitis from carcinoma of the sigmoid. PMID- 8010254 TI - Differentiating colonic polyps from air bubbles on barium enema: the "carpenter's level sign". PMID- 8010251 TI - Preoperative assessment of gastric carcinoma: value of two-phase dynamic CT with mechanical iv. injection of contrast material. AB - OBJECTIVE: The purpose of this study was to evaluate the utility of two-phase dynamic CT performed with mechanical IV injection of a bolus of contrast medium after oral intake of water in the preoperative staging of gastric cancers. SUBJECTS AND METHODS: We performed incremental dynamic CT in 52 patients with pathologically proved gastric cancers. Dynamic CT findings were prospectively analyzed and correlated with surgical and histopathologic findings. A total of 150 ml of nonionic contrast medium was administered IV with a power injector at a flow rate of 5 ml/sec for 30 sec, and two-phase images were obtained at 30 sec (early phase) and 2 min (equilibrium phase) after the start of bolus injection. RESULTS: Forty-one advanced gastric carcinomas showed a moderate to marked degree of heterogeneous enhancement in the early phase and homogeneous enhancement of the entire lesion in the equilibrium phase of dynamic CT. The primary tumors were correctly detected with dynamic CT in five (56%) of the nine early gastric cancers and in 41 (95%) of the 43 advanced gastric cancers. The overall detection rate of gastric cancers was 88% (46 of 52 cases). The accuracies of dynamic CT according to TNM staging in determining the depth of tumor invasion, the degree of serosal invasion, and regional lymph node metastasis were 65% (34 of 52 cases), 83% (38 of 46 cases), and 70% (32 of 46 cases), respectively. CONCLUSION: Our findings show that two-phase incremental dynamic CT with mechanical IV injection of a bolus of contrast medium after oral intake of water improves the diagnostic accuracy of CT over that provided by conventional CT in the preoperative staging of gastric cancers. PMID- 8010256 TI - Recurrent tumor after resection of hepatic metastases from colorectal carcinoma: location and time of discovery as determined by CT. AB - OBJECTIVE: Despite studies showing increased survival rates for patients after surgical resection of hepatic metastases, recurrences occur in 75% of treated patients. The purpose of this study was to determine the location and time of discovery of recurrent tumor on CT scans after resection of hepatic metastases from colorectal carcinoma. MATERIALS AND METHODS: In a 6-year period, 32 patients (16 men and 16 women) who had undergone partial hepatic resection for colorectal metastases had follow-up CT at our institution. A total of 125 CT examinations of the chest and abdomen were retrospectively reviewed for the presence and location of recurrent disease. Recurrence was either confirmed by biopsy (n = 12) or presumed on the basis of growth of new lesions (n = 17). RESULTS: With a mean follow-up of 22 months (range, 1-60 months), recurrence was found at 29 sites in 25 patients. Thirteen sites were hepatic, and 16 were extrahepatic. Three patients had both hepatic and pulmonary disease. Recurrence within the liver was away from surgical margins in 11 (85%) of 13 patients at 14 +/- 7 months and adjacent to a surgical margin in the remaining two patients (15%) at 17 +/- 1 months. Extrahepatic recurrences were discovered in the lung in 11 (69%) of 16 patients at 21 +/- 12 months; in an adrenal gland in two patients (13%) at 19 +/- 5 months; in lymph nodes of the porta hepatis in one patient (6%) at 11 months; at the primary colonic anastomosis in one patient (6%) at 3 months; and in a retroperitoneal lymph node in the remaining patient (6%) at 12 months. CONCLUSION: Surgery was effective in treating the preoperatively detected hepatic metastases. Only two of 25 patients had recurrence related to a hepatic surgical margin. Most recurrences occur more than 1 year after surgery, most often in lung or liver away from surgical margins, and they probably represent small metastases undetectable with current preoperative or intraoperative techniques. PMID- 8010255 TI - Contrast-enhanced spiral CT of the liver: effect of different amounts and injection rates of contrast material on early contrast enhancement. AB - OBJECTIVE: Spiral CT allows rapid hepatic imaging during a single breath-hold. The increase in imaging speed potentially allows contrast material to be used more efficaciously than with conventional dynamic CT, perhaps allowing a decrease in the volume of required contrast agent. To determine how this can be accomplished, we studied the effect of different bolus IV injection rates and amounts of contrast material on early hepatic enhancement during dynamic bolus spiral CT. SUBJECTS AND METHODS: A group of 20 healthy male volunteers were divided into four groups of five each. The groups received 75, 100, 125, or 150 ml of contrast material (Omnipaque 300, 300 mg l/ml). Each person within each group was scanned as contrast material was injected at rates of 3, 4, and 5 ml/sec. Hepatic enhancement was evaluated by comparing quantitative regions of interest before and after bolus injection of contrast material. Variations in enhancement produced by changes in volume and injection rate of contrast material were evaluated on early, middle, and late sections of the spiral, corresponding to 32-34, 41-43, and 51-53 sec, respectively, after the injection of contrast material was begun. RESULTS: Hepatic enhancement increased more rapidly when the bolus of contrast material was given at a rate of 5 ml/sec than at the slower rates of 3 or 4 ml/sec. Enhancement of the liver was greatest at the late portion of the spiral (51-53 sec after start of the bolus injection), averaging 73 and 79 H for volumes of 125 and 150 ml, respectively, at 5 ml/sec, and the enhancement was still increasing at that time. Enhancement curves predict 50- and 70-H mean increases in hepatic attenuation on initial slices with scan delays of approximately 40 and 50 sec, respectively, for these two protocols. CONCLUSION: Our results demonstrate that there is a marked dependence on early hepatic enhancement produced by variations in volume and injection rate of contrast material. We found no difference in the results produced by 125- and 150-ml volumes. These results are important for maximizing the effectiveness of IV contrast material during rapid hepatic spiral CT scanning. PMID- 8010257 TI - Ileal duplication cyst. PMID- 8010259 TI - The blood-brain barrier: an important concept in neuroimaging. PMID- 8010258 TI - Surgical segmental anatomy of the liver: demonstration with spiral CT during arterial portography and multiplanar reconstruction. AB - A major role of imaging in the evaluation of hepatic tumors is to assist surgeons in the preoperative determination of the feasibility of hepatic resection. Although the segmental location of tumors is not the sole criterion for determining resectability, such knowledge is useful for preoperative planning of the type of resection. This essay illustrates the surgical segmental and subsegmental anatomy of the liver as shown by spiral CT during arterial portography (CTAP) with multiplanar reformation. PMID- 8010260 TI - Revisiting the blood-brain barrier. PMID- 8010261 TI - MR assessment of radiation-induced blood-brain barrier permeability changes in rat glioma model. AB - PURPOSE: To assess the potential of a T1-weighted, gadolinium-enhanced MR technique for quantifying radiation-induced changes of blood-brain barrier permeability in a model of stereotactically implanted intracerebral gliomas in rats. METHODS: We calculated the gadolinium blood-to-tissue transport coefficient for gadopentetate dimeglumine from signal intensities in sequential MR images in nine control animals that were not irradiated and in five and three animals that had received 2500 cGy and 1500 cGy whole-brain irradiation, respectively, at 2 days before imaging. RESULTS: The average blood-to-tissue transport coefficient values were 9.76 mL.kg-1.min-1 in the control group, 23.41 mL.kg-1.min-1 in the 2500 cGy group, and 25.63 mL.kg-1.min-1 in the 1500-cGy group. Blood-to-tissue transport coefficients were significantly higher after irradiation, indicating increased radiation-induced blood-brain barrier permeability. Similar increased blood-brain barrier leakiness in brain tumors after high-dose irradiation has been shown by previous nuclear medicine studies using quantitative autoradiography. CONCLUSION: Contrast-enhanced dynamic MR of brain gliomas is a sensitive method to document radiation-induced blood-brain barrier breakdown. Quantitative gadolinium-enhanced MR may become a useful tool for the management of patients with brain tumors undergoing radiation therapy. PMID- 8010263 TI - Gadolinium enhancement of the leptomeninges caused by hydrocephalus: a potential mimic of leptomeningeal metastasis. AB - A patient had severe hydrocephalus and diffuse leptomeningeal enhancement on MR which mimicked leptomeningeal spread of a primary brain tumor. The leptomeningeal enhancement resolved completely after decompression of the hydrocephalus. Data suggest that the leptomeningeal enhancement is caused by vascular stasis induced by the hydrocephalus. PMID- 8010265 TI - Congenital arteriovenous fistulas supplied by a single branch of the maxillary artery. AB - We report four cases (two children, two adults) of congenital arteriovenous fistula supplied by a single large (pterygoid) branch of the second part of the maxillary artery deep to the parotid gland and mandible, with emphasis on the angiographic findings, therapeutic implications, and cause, with a review of the literature. Awareness of a predilection of congenital arteriovenous fistulas for this site, excellent-quality selective angiography, and careful attention to flow patterns help make the correct diagnosis. Endovascular balloon occlusion is the preferred treatment. PMID- 8010262 TI - Frequency of unexplained meningeal enhancement in the brain after lumbar puncture. AB - PURPOSE: To examine the hypothesis that lumbar puncture alone may cause meningeal enhancement in the brain. METHODS: We prospectively reviewed the brain MR examinations of all patients from a 6-month period who were studied within 1 month after lumbar puncture. We also retrospectively reviewed all cases of dural arachnoidal enhancement in the brain from the preceding 18-month period. RESULTS: In the prospective group, only one case out of 97 enhanced brain MR examinations after lumbar puncture did not have a clear cause for dural-arachnoidal enhancement. In the retrospective group, only one case out of 11 with enhancement was not clearly explained. CONCLUSIONS: Dural-arachnoidal enhancement in the brain after lumbar puncture is uncommon, if it occurs at all, and lumbar puncture as a cause of enhancement should be considered a rare diagnosis of exclusion. PMID- 8010266 TI - Imaging quiz. Intravenous drug use; multiple broken needle tips in the neck. PMID- 8010264 TI - Posterior fossa venous angiomas with drainage through the brain stem. AB - PURPOSE: To describe 11 cases of posterior fossa venous angiomas with drainage through the brain stem. METHODS: Eleven cases of posterior fossa venous angioma with drainage through the brain stem were evaluated using MR. Correlation with known routes of venous drainage for the cerebellum and brain stem is made. RESULTS: Six of the 11 venous angiomas were found in the cerebellum, four in the brain stem; one involved both the cerebellum and brain stem. The cerebellar venous angiomas drained to subependymal veins about the fourth ventricle and dorsal pons. These then connected with an enlarged transmesencephalic or transpontine vein, to drain anteriorly to the anterior pontine veins. The brain stem angiomas had variable drainage depending on location. Evidence of hemorrhage was seen in five cases. CONCLUSION: Cerebellar and brain stem venous angiomas have several potential routes of drainage, including an enlarged vein traversing the pons, midbrain, or medulla. A knowledge of the normal venous anatomy of this region helps to understand the occurrence of these uncommon routes of venous drainage. PMID- 8010267 TI - Acetazolamide challenge for three-dimensional time-of-flight MR angiography of the brain. AB - PURPOSE: We compared three-dimensional time-of-flight MR angiograms obtained before and after acetazolamide administration to evaluate whether use of this drug could improve visualization of small peripheral intracranial arteries and atherosclerotic stenosis. METHODS: For evaluation of small peripheral arteries, 10 patients with clinical diagnosis of ischemic cerebrovascular disease and 10 healthy volunteers were investigated, and for evaluation of stenosis, another 6 patients were investigated. Vascular images were obtained by three-dimensional time-of-flight MR angiography. After a baseline scan, 17 mg/kg acetazolamide was injected intravenously and the second scan was performed 20 minutes later. RESULTS: Several small peripheral arteries that had not been seen on the baseline images were visible on the acetazolamide images without any augmentation of the background signals. Stenotic lesions in the main trunks of the major cerebral arteries were detected more clearly on acetazolamide images. CONCLUSIONS: Acetazolamide improves visualization of small peripheral intracranial arteries and sensitivity in detecting atherosclerotic stenosis in the main trunk of major cerebral artery by three-dimensional time-of-flight MR angiography without changing MR apparatus and software. PMID- 8010268 TI - Evaluation of shared-view acquisition using repeated echoes (SHARE): a dual-echo fast spin-echo MR technique. AB - PURPOSE: To compare the clinical efficacy of a dual-echo fast spin-echo imaging technique, SHARE (share-view acquisition using repeated echoes), with conventional long-repetition-time spin-echo imaging. METHODS: Conventional spin echo and SHARE fast spin-echo MR images of the brain were acquired in 50 randomized patients and interpreted separately in conjunction with the T1 weighted images. All images were reviewed independently by two neuroradiologists who were blinded to the clinical history and previous interpretations. RESULTS: The diagnoses rendered for the spin-echo and SHARE images were concordant in 48 of the 50 subjects (96%) by the first reader and in all 50 cases (100%) by the second reader. SHARE images were acquired in one-fourth of the imaging time yet image contrast, quality, and sensitivity to long T2 lesions were comparable. The SHARE technique was less sensitive to hemorrhagic residua. CONCLUSIONS: SHARE is a viable time-saving alternative to the conventional long-repetition-time pulse sequence. Although SHARE images are not as sensitive to magnetic susceptibility effects, the time saved using this technique could be used to perform a gradient echo sequence when indicated. PMID- 8010269 TI - Pituitary gland MR: a comparative study of healthy volunteers and patients with microadenomas. AB - PURPOSE: To compare the MR appearance of the pituitary glands of healthy volunteers with that of patients with microadenomas. METHODS: Unenhanced coronal T1-weighted MR of the pituitary gland was performed on 52 healthy adult volunteers and 14 consecutive patients with evidence of pituitary adenomas. The MRs were interpreted in a randomized, blinded fashion. Notation was made of pituitary gland size, symmetry, stalk position, and the gland's signal uniformity. RESULTS: Focal pituitary gland hypointensities were seen in 20 of 52 volunteers and in all 14 patients. In the volunteers, on average the areas of low signal were smaller and not as dark as in the patient group, but there was some overlap between the two groups. Pituitary gland size, symmetry, and stalk position did not differ between the two groups. CONCLUSIONS: Focal hypointensities are common incidental MR findings in the healthy population. On average they appear smaller and not as dark as microadenomas. PMID- 8010270 TI - Cerebral MR in ophthalmoplegia plus. AB - PURPOSE: To evaluate MR patterns in ophthalmoplegia plus and correlate them with clinical symptoms. METHODS: MR was performed on a 1.5-T whole-body scanner with T2-weighted gradient-echo and spin-echo images. The retrospective analysis included 19 patients with clinically established diagnoses of ophthalmoplegia plus. RESULTS: Two types of cerebral MR abnormalities were found in ophthalmoplegia plus: brain atrophy and hyperintensities restricted to the white matter and basal ganglia, which appeared as either focal or diffuse areas of high signal intensity and were of strictly supratentorial location. No specific distribution was found. These findings differ markedly from infarction-like lesions found in mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes. CONCLUSIONS: MR is sensitive for the detection of central nervous system involvement in ophthalmoplegia plus, but findings are nonspecific. However, cerebral MR in ophthalmoplegia plus is different from other mitochondrial encephalomyopathies and underlines the clinical differentiation of mitochondrial encephalomyopathies. PMID- 8010271 TI - Lack of age-related differences in temporal lobe volume of very healthy adults. AB - PURPOSE: To evaluate age-related differences in temporal and supratemporal brain regions in carefully selected, very healthy men 19 to 92 years of age. METHODS: MR quantification of brain regions used image segmentation into cerebrospinal fluid and brain matter based on nonlinear modeling of pixel intensity distributions. RESULTS: There was a significant age-related decrease (approximately 1% per decade) of posterior frontal lobe volume, but not of temporal lobe volume. The mean volume of the right temporal lobe was significantly greater than the left, and this relation did not change with age. CONCLUSION: In very healthy aging, the volume of the temporal lobes remains constant over the age range of human life. PMID- 8010272 TI - Neurosonographic abnormalities associated with maternal history of cocaine use in neonates of appropriate size for their gestational age. AB - PURPOSE: To determine whether increased incidence of neurosonographic abnormalities (predominantly of the basal ganglia and thalamus) in cocaine exposed neonates who are small for their gestational age is attributable to the cocaine or to neonatal size. METHODS: Neonates whose sizes were appropriate for their gestational age with no evidence of hypoxia or respiratory distress were identified prospectively by a maternal history of cocaine use. Scans were performed within 72 hours of birth using a 7.5-MHz transducer following a standard protocol. The images were analyzed without access to patient information. Forty study neonates were compared with 34 control subjects who were appropriate in size for their gestational age, scanned using the same protocol. Comparisons were made using Fisher Exact Test, t test, and logistic regression. RESULTS: No control infant had neurosonographic abnormalities. In the study group, gestational age ranged from 27 to 41 weeks. Of the 40 study neonates, 14 (35%) had one neurosonographic abnormality; two had two abnormalities. The predominant lesion was focal echolucencies, mainly in the area of the basal ganglia (10 of 40, 25%). Other findings were caudate echogenicity (3 of 40, 7.5%), ventricular dilation (2 of 40, 5%) and one "moth-eaten" appearance of the thalamus. Lesions were more likely approaching term and were not related to prematurity or alcohol use. CONCLUSION: Apparently normal neonates with a maternal history of cocaine use are likely to have degenerative changes or focal infarctions in their basal ganglia attributable to cocaine. Neurosonography should be used to evaluate these neonates. The long-term significance of these lesions needs further evaluation. PMID- 8010273 TI - Congenital cytomegalovirus infection of the brain: imaging analysis and embryologic considerations. AB - PURPOSE: To analyze the cortical gyral patterns and myelination patterns in a series of patients with congenital cytomegalovirus infections involving the central nervous system, to correlate them with known developmental events, and to develop a consistent theory regarding their embryogenesis. METHODS: The MR (11 patients) and CT (four patients) studies of 11 patients with congenital cytomegalovirus infections involving the brain were retrospectively reviewed. Analysis was made of myelination patterns, cortical gyral patterns, other areas of maldeveloped brain, and focal brain lesions. RESULTS: Lissencephaly was found in four patients. These patients had very thin cerebral cortices, extremely diminished volume of white matter, delayed myelination, small cerebella, and very enlarged lateral ventricles. Focal areas of dysplastic cortex, presumably polymicrogyria, were found in five patients. These patients had slightly thickened irregular cerebral cortices, slightly diminished volume of white matter, delayed myelination, variably small cerebella, and slightly enlarged lateral ventricles. Two patients had normal cerebral cortices, slightly diminished volume of white matter, delayed myelination, normal cerebella, and slightly enlarged lateral ventricles. Periventricular lesions, representing calcification, or perhaps blood, were seen in all groups. CONCLUSIONS: We postulate that the patients with lissencephaly suffer injury before 16 or 18 weeks gestational age, whereas those with regions of polymicrogyria are injured between approximately 18 and 24 weeks gestational age. Those with normal gyral patterns are probably injured during the third trimester and may have active infections at birth. Moreover, we propose that the finding of cerebellar hypoplasia and myelination delay in association with diffuse lissencephaly or cortical dysplasia should suggest the diagnosis of congenital cytomegalovirus infection. PMID- 8010274 TI - Papaverine-induced mydriasis. AB - Five cases of ipsilateral pupillary dilatation that developed during local intraarterial infusion of papaverine are reported. All patients were being treated for symptomatic vasospasm secondary to subarachnoid hemorrhage. In each case, the tip of the infusion catheter was positioned in the internal carotid artery in close proximity to the ostium of the ophthalmic artery. Pupillary dilatation in all patients readily resolved after termination of the infusion. PMID- 8010275 TI - Transient severe brain stem depression during intraarterial papaverine infusion for cerebral vasospasm. AB - A 63-year-old woman had severe, symptomatic cerebral vasospasm secondary to subarachnoid hemorrhage. We initiated simultaneous infusions of papaverine into her left vertebral and left internal carotid arteries. Twenty-five minutes after the infusions had begun, the patient had a transient reaction of respiratory arrest followed by rapid, progressive loss of brain stem function. PMID- 8010276 TI - [15O]H2O positron emission tomography determination of cerebral blood flow during balloon test occlusion of the internal carotid artery. AB - PURPOSE: To determine the utility of [15O]H2O positron emission tomography (PET) for the quantitative determination of cerebral blood flow in patients undergoing balloon test occlusion of the internal carotid artery. METHODS: Twenty-two [15O]H2O PET cerebral blood flow studies were completed on 20 patients for whom temporary or permanent occlusion of the internal carotid artery was being considered because of skull base tumor or internal carotid artery aneurysm. In each study, cerebral blood flow was determined during temporary balloon internal carotid artery occlusion, and again after deflation and removal of the balloon from the internal carotid artery. RESULTS: Patients were divided into three groups based on clinical and cerebral blood flow response to balloon test occlusion. Studies were classified as group I when associated with no clinical symptomatology and with a cerebral blood flow decrease of less than 10 mL/100 g per minute (16 of 22 patients); as group II when there was no clinical symptomatology and cerebral blood flow fell to 25 to 35 mL/100 g per minute on the occluded side (5 of 22); and as group III when the patient was clinically unable to tolerate test occlusion and had a cerebral blood flow of less than 20 mL/100 g per minute on the occluded side (1 of 22). Neurologic sequelae developed in none of the eight group I patients later undergoing permanent internal carotid artery occlusion. Cerebral infarction developed subsequently in the one group II patient who underwent internal carotid artery occlusion. CONCLUSION: During internal carotid artery balloon test occlusion, [15O] H2O PET determination of cerebral blood flow allows rapid quantitative determination of cerebral blood flow throughout the entire brain, predicting the adequacy of collateral flow after permanent occlusion. All patients were able to tolerate the [15O]H2O PET cerebral blood flow determination, and there were no complications of the procedure. PMID- 8010277 TI - Blood flow dynamics in the vertebrobasilar system: correlation of a transparent elastic model and MR angiography. AB - PURPOSE: To describe the flow patterns in a model of the vertebrobasilar artery and use these observations to explain the appearance of the flow on the MR images. METHODS: We created an anatomically precise, transparent elastic model of the human vertebrobasilar artery containing a basilar tip aneurysm and perfused the model with non-Newtonian fluid which has similar rheologic properties to blood. Flow patterns in the vessels were directly observed. MR angiogram images were obtained with commercially available two-dimensional time-of-flight, three dimensional time-of-flight, and 3-D phase-contrast MR angiographic pulse sequences, and they were correlated with the directly seen flow patterns. Quantitative flow velocity measurements were performed with 2-D cine phase contrast MR angiography and correlated with the flow measured with an electromagnetic flow meter. RESULTS: Visualization studies showed the dye stream patterns in the vertebrobasilar arteries to be extremely complex and variable. During the MR experiments we found that often the same segment of a vessel could appear very different depending on the pulse sequence. In some instances, the model experiments helped to explain the MR appearance of the vessels. Flow profiles measured with 2-D cine phase contrast were found to be consistent with those measured directly with an electromagnetic flow meter. CONCLUSION: Clear elastic models can be used to duplicate the flow in human cranial vessels and thus provide a unique means to observe these flow patterns directly. The flow patterns helped to explain the variation in appearance of the vessels and the artifacts with different MR angiography pulse sequences. The artifacts depend on both the geometry of the vessel and the flow pattern within it. Two-dimensional cine phase-contrast MR provides temporal flow field information that is directly related to physiological information about flow volumes and velocity patterns. PMID- 8010278 TI - Progressive posttraumatic myelomalacic myelopathy: imaging and clinical features. AB - PURPOSE: To describe the imaging features, surgical management, and clinical outcome of progressive posttraumatic myelomalacic myelopathy (PPMM), a relatively unrecognized but important cause of progressive myelopathy in patients with previous spinal cord injuries. METHODS: The clinical records, imaging studies, and postoperative outcome of 10 patients with PPMM were reviewed. Fifteen preoperative and five postoperative MRs were analyzed for intramedullary signal abnormalities, the nature of these signal abnormalities, and cord tethering. All patients had intraoperative sonography. RESULTS: Neurologic signs and symptoms found in our patients included 1) progressive loss of motor function (6/10), 2) sensory level changes (4/10), 3) increased spasticity (4/10), 4) autonomic dysreflexia (4/10), 5) loss of bowel or bladder control (4/10), and 6) local and/or radicular pain (4/10). Preoperative MR in nine patients revealed intramedullary T1/T2 lengthening (9/9), extramedullary tethering/adhesions (9/9), ill-defined lesional borders (6/9), cord expansion (5/9), and increased signal intensity of the lesion on T1-weighted images compared with CSF (7/9). Proton density images in five patients demonstrated a relative increase in signal intensity over CSF. In all five postoperative MRs, there was evidence of untethering of the spinal cord and a decrease in cord size in two patients. Intraoperative sonography revealed cord tethering and abnormal cord echotexture in all cases. Postoperative clinical evaluation revealed neurologic improvement in nine patients. CONCLUSIONS: PPMM may clinically and radiographically mimic progressive posttraumatic cystic myelopathy (PPCM). MR provides clues to the diagnosis of myelomalacia preoperatively. Intraoperative sonography confirms the absence of a confluent cyst. These points are crucial in the surgical procedures in PPMM vs PPCM. In PPMM, lysis of intradural adhesions results in an improvement in symptoms in a manner similar to the shunting of PPCM. PMID- 8010279 TI - CT and MR of temporal bone malignancies primary and secondary to parotid carcinoma. AB - PURPOSE: To review the CT and MR characteristics of temporal bone malignancy, and to evaluate the relationship between malignancies of the temporal bone and parotid gland. METHODS: A group of 15 surgical patients with diagnosis of temporal bone malignancy were retrospectively reviewed. These included 11 cases of primary temporal bone malignancy and four cases of secondary carcinoma of the temporal bone from a primary tumor of the parotid gland. Three primary temporal bone malignancies were recurrences, and two secondary tumors were parotid recurrences. RESULTS: Five of the 11 patients with primary temporal bone malignancy had parotid infiltration (45%). All four patients with secondary temporal bone destruction caused by parotid carcinoma had erosion of the mastoid, two with erosion of the external auditory canal, and one of the middle ear. CONCLUSIONS: It is important radiographically to recognize the close relationship between malignancies of the temporal bone and parotid gland, because either may secondarily invade the other. Suspicion of malignancy in either the temporal bone or parotid gland necessitates complete imaging of the other structure. Temporal bone or skull base erosion were best seen on CT at bone algorithm. MR with and without infusion provided excellent delineation of soft-tissue tumor margins, muscle infiltration, intracranial extension, and vascular encasement. PMID- 8010280 TI - Subcortical hemorrhage in disseminated intravascular coagulation associated with sepsis. AB - Cranial CT features of two patients with intracerebral hemorrhages in the setting of sepsis and disseminated intravascular coagulation are reported. Multiple predominantly subcortical hemorrhages were seen. This pattern of cerebral hemorrhage should raise suspicion of disseminated intravascular coagulation as an underlying cause. PMID- 8010281 TI - MR of the head and neck: comparison of fast spin-echo and conventional spin-echo sequences. AB - PURPOSE: To compare conspicuousness of head and neck lesions on fast spin-echo sequences and conventional spin-echo sequences. METHODS: Forty consecutive patients with 61 head and neck lesions were evaluated. Lesion conspicuousness was qualitatively compared on conventional spin-echo and fast spin-echo sequences, using both spin-density and T2-weighted images. Thirty-six lesions had surgical or pathologic confirmation, and 25 were assigned a presumptive diagnosis based on clinical evaluation and imaging findings seen on conventional spin-echo T1- and T2-weighted sequences. Forty lesions were related to neoplasms; 21 lesions consisted of infectious, vascular, or inflammatory abnormalities. RESULTS: Fast spin-echo sequences provided improved lesion conspicuousness in 91% of spin density images, in 77% of T2-weighted images, and in 84% of the combined spin density and T2-weighted images. CONCLUSION: By providing shorter imaging times and equal or superior lesion conspicuousness, long-repetition-time fast spin-echo sequences can replace long-repetition-time conventional spin-echo sequences in evaluation of the head and neck. PMID- 8010282 TI - Orbital and optic pathway sarcoidosis: MR findings. AB - PURPOSE: To identify and characterize the MR findings of sarcoidosis when it involves the orbit and visual pathways. METHODS: The MR scans of 15 patients, 3 with presumed and 12 with proved orbital or optic pathway sarcoidosis were retrospectively reviewed. RESULTS: Eight patients had MR evidence of optic nerve involvement by sarcoid granuloma. Perineural enhancement was seen in four cases, optic atrophy in one. Three who had had unenhanced scans showed optic nerve enlargement. Nine patients had optic chiasmal involvement. One patient had increased T2 signal in the optic radiations. Three patients had orbital masses that had MR signal characteristics similar to pseudotumor. Five patients had periventricular white matter abnormalities closely resembling multiple sclerosis. CONCLUSIONS: Sarcoidosis should be considered in the differential diagnosis of optic nerve or nerve sheath enhancement on MR. Orbital sarcoidosis has MR characteristics very similar to pseudotumor. PMID- 8010283 TI - Inflammatory pseudotumor of the maxillary sinus in a 15-year-old boy. AB - Inflammatory pseudotumor is a benign neoplasm composed of fibroblasts, histiocytes, and inflammatory cells. Its occurrence in the paranasal sinuses is rare. We report a case of a 15-year-old boy with a maxillary sinus inflammatory pseudotumor that simulated an aggressive neoplasm on CT scan. PMID- 8010284 TI - Use of xenon and ultrafast CT to measure cerebral blood flow. PMID- 8010285 TI - The "hypoteloric happy face" sign: a misleading indicator of complete aneurysm closure with Guglielmi detachable coils. PMID- 8010287 TI - The role of nurses in the new health care order. PMID- 8010286 TI - Annotated bibliography. PMID- 8010289 TI - Health care in Grenada. Project HOPE's mental health program: psychiatric nursing aspects. PMID- 8010288 TI - A life in international health care. PMID- 8010290 TI - Health care reform in context. A brief overview of the role of nurses in the U.S. health care system, 1946-1994. PMID- 8010291 TI - To nurse the nurses. The formation of the Alumni Association of the Presbyterian Hospital Training School for Nurses, 1899. PMID- 8010292 TI - Investigation of a spontaneous abortion cluster: lessons learned. AB - An investigation of a reported spontaneous abortion excess in an office environment was undertaken employing a multidisciplinary approach, including (1) an epidemiologic/validation step; (2) an industrial hygiene survey, including electromagnetic field measurements and indoor air quality determinations; and (3) a risk perception/risk communication component. This approach was needed because there are numerous chemical and physical agents and psychosocial stressors that may potentially impact the reproductive status of female office workers. Although video display terminals (VDTs) are typically the focus of spontaneous abortion (SAB) investigations, one cannot ignore other stressors in the environment. Magnetic field exposures within a payroll area were determined using a hand-held survey meter and data logging dosimeter. On average, the full shift time-weighted average exposures of workers to extremely low frequency (ELF) magnetic fields in the payroll office area ranged from 1.0 to 5.6 mG. Influencing the investigation's protocol design were the Centers for Disease Control's (CDC's) recent Guidelines for Investigating Clusters of Health Events. Although these guidelines grew primarily out of cancer cluster investigations, we applied them in this instance and found them to be generalizable to reproductive hazards investigations. A spontaneous abortion excess was validated over a 2-year period among 26 women with 32 reproductive events, with rates 1.5-2.5 times the expected, depending on comparison figures used. Lessons learned in the investigation, including the applicability of the CDC's Cluster Investigation Protocol and the enormous importance of risk perception and risk communication, are described. PMID- 8010293 TI - Lung cancer mortality and airways obstruction among metal miners exposed to silica and low levels of radon daughters. AB - Starting from a cross-sectional survey in 1973, the mortality of two cohorts of Sardinian metal miners was followed through December 31, 1988. In mine A, the quartz concentration in respirable dust ranged between 0.2% and 2.0% and the exposure to radon daughters averaged 0.13 working level (WL), with the highest estimated cumulative exposure around 80-120 WLM. In mine B, the silica content was much higher (6.5-29%), but exposure to radon daughters was significantly lower than in mine A. More than 98% of the overall work force in 1973 (1,741 miners) entered the cohort, providing 25,842.5 person-years. Smoking, occupational history, chest radiographs, and lung function tests were available for the cohort members at admission. Mortality for all causes was slightly lower than expected. A significant excess for nonmalignant chronic respiratory diseases was noticed in both mines. Twenty-four subjects died of lung cancer, 17 from mine A (SMR: 128; 95% confidence interval [CI]: 75-205) and 7 from mine B (SMR: 85; 95% CI: 34-175). The SMR for lung cancer was highest among the underground workers from mine A (SMR: 148; 95% CI: 74-265), with a significant upward trend by duration of employment in underground jobs. Mine B underground miners showed lung cancer SMRs close to 100 without a significant trend by duration of employment. Among underground miners with spirometric airways obstruction in 1973, those from mine A showed the highest risk (SMR: 316; 95% CI: 116-687). The relationship did not change after adjusting for age and smoking. Based on the present findings, crystalline silica per se does not appear to affect lung cancer mortality. A slight association between lung cancer mortality and exposure to radon daughters, though within relatively low levels, may be considered for underground miners from mine A. Impaired pulmonary function may be an independent predictor of lung cancer and an important risk factor enhancing the residence time of inhaled carcinogens, i.e., alpha particles or PAHs, by impairing their bronchial and alveolar clearance. PMID- 8010294 TI - Personal history, training, and worksite as predictors of back pain of nurses. AB - Back pain among nurses is a common problem. Prior studies of this problem have been based on cross-sectional or retrospective data. This 18-month prospective study involving nurses newly graduated from nursing school investigated personal, worksite, and training factors associated with future risk of back pain. Each nurse underwent a preliminary interview and periodic follow-ups to identify those with back injuries. Contingency tables and logistic regression analyses demonstrated that prior significant back pain episodes (evidenced by previous job changes because of back pain, frequent medication use, etc.) were associated with increased future risk. Training at nursing school or on the job did not have a protective effect. This pilot study therefore suggests factors useful in placement and counseling of new nurses and indicates the need for further implementation of mechanical lift assist device use. PMID- 8010295 TI - Outcome of carpal tunnel surgery in Washington State workers' compensation. AB - All cases of occupational carpal tunnel syndrome (OCTS) who received surgery for this condition in the Washington State workers' compensation system were identified using claim and physician billing databases. One hundred ninety-one incident surgical cases were identified between July 1, 1987 and December 31, 1987, and were followed up a mean of 3 years postoperatively for clinical, disability, and return to work outcomes. Medical record and claim file review was required for clinical and employment information. The mean age of all patients was 36.6 years, 48% were female, and 40% received bilateral surgery. The mean time from claim filing to surgery was 187 days. Ninety-eight percent of cases met the National Institute for Occupational Safety and Health (NIOSH) case definition for OCTS. Relief of pain was complete or modest in 86% (124/145) and only 14% of cases reported no improvement in symptoms. Mean duration of disability (time loss) postoperatively was nearly 4 months, and 8% of cases exceeded 1 year of time loss. The majority of cases returned to their same job (67%) or to a different job (15%). Workers in high risk occupations were less likely to return to the same job after CTS surgery compared to those in lower risk occupations (61% vs. 75%, p = 0.08). In this population, no association was seen between any outcome and age, gender, marital status, or baseline wage. Duration of disability was not significantly related to preoperative severity of OCTS or to more specific case criteria for this condition.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8010296 TI - Extended mortality follow-up among men and women in a U.S. furniture workers union. AB - The addition of 5 years of follow-up and over 411,000 person-years of observation to a cohort of 34,081 men and women employed in U.S. furniture and other related industries allowed the investigation of mortality patterns among women and minority races in addition to white men. A significant excess of pleural mesotheliomas occurred among white men (standardized mortality ratio [SMR] = 3.7, 95% confidence interval [CI] = 1.2-8.7) but could not be linked to a particular type of furniture manufacturing. SMRs for myeloid leukemia and chronic nephritis were elevated among white men employed in the wood furniture industry but were not statistically significant. Males in the black/other race categories in wood furniture plants showed nonsignificant mortality excesses for infectious diseases and cancers of the prostate and colon and rectum. Among white women employed in wood furniture plants, mortality was elevated for cancers of the pancreas and lung during the most recent follow-up period. In metal furniture plants, mortality was raised among men in both race groups for kidney cancer (black/other SMR = 8.0, 95% CI = 1.6-23.2; white SMR = 2.1, 95% CI = 0.4-6.2) and diabetes mellitus (black/other SMR = 2.2, 95% CI = 0.6-5.6; white SMR = 1.8, 95% CI = 0.7 3.9). Stomach cancer mortality was significantly elevated (SMR = 3.3, 95% CI = 1.3-6.8) among white men in metal furniture plants and was of the same magnitude over both the previous and the most recent follow-up periods. Among those working with textiles, SMRs were significantly elevated for leukemia (SMR = 6.1, 95% CI = 1.2-7.8) and cancers of the colon and rectum (SMR = 3.2, 95% CI = 1.3-4.5) for white women. Lung cancer mortality was increased for white men and women in textile operations, but SMRs were not statistically significant. SMRs for a number of other causes of death that were elevated at the end of the earlier follow-up period were not increased during the new follow-up period. PMID- 8010297 TI - Acute effects on forced expiratory volume in one second and longitudinal change in pulmonary function among wood trimmers. AB - Wood trimmers are exposed to molds that periodically grow on timber, and may develop acute as well as chronic pulmonary function impairment. This study examined whether these acute changes in pulmonary function are predictors for a longitudinal deterioration in pulmonary function, beyond normal aging and exposure. Across-shift changes in pulmonary function, measured during a working week, were evaluated in 15 wood trimmers with a follow-up time of 27 months. Twenty-six sawmill workers, employed at the same plants as the wood trimmers, served as control subjects. The highest concentration of viable mold spores for the wood trimmers was 10(6) colony-forming units (cfu)/m3, i.e., several times higher than the corresponding value for the sawmill workers. At the follow-up, wood trimmers had a lower forced vital capacity (FVC) on average, after adjustment for age and height, compared to the sawmill workers. In addition, a correlation was found between the across-week change in forced expiratory volume in 1 second (FEV1) and the decline in FEV1 between the first and the second occasion, after adjusting for normal aging in nonsmoking wood trimmers (r2 = 84%, p < 0.001). The results from the present study suggest that across-shift decrease in FEV1 (measured during a working week) might serve as a guide to identify subjects being at risk for a further decrement in pulmonary function over and above the effects of normal aging and exposure to mold spores in the wood trimming department. PMID- 8010299 TI - Dairy barns and roll-over protection on farm tractors: work environment impacts on the adoption of roll-over protective structures. AB - A mailed survey of one group of dairy farmers supports the informal perception that roll-over protective structure (ROPS)-equipped tractors are considered unusable for in-barn tasks. This attitude must be addressed in order to achieve greater use of safety equipment. PMID- 8010298 TI - Estimation of long-term exposure to pesticides. AB - Quantifying the exposure of agricultural workers to pesticides is difficult in the face of the heterogeneity of the pesticides used, the variability in methods of application, and the lack of adequate exposure data. This report describes an attempt to estimate long-term dermal and inhalation exposure of bulb farmers by the development of an exposure index. This proposed exposure index consists of generic levels of exposure specific to the method of application, which were derived from databases as well as from field studies. The index is further determined by farm-related parameters such as acreage and number of pesticide applications ascertained from questionnaire responses. A widely used dithiocarbamate mixture served as a marker compound for exposure to other pesticides. Ranking of 127 bulb farmers according to calculated lifetime dermal exposure correlated only moderately to ranking based on duration of exposure, e.g., years of exposure and farm acreage. This finding indicates that the proposed exposure index could provide a useful estimate of long-term exposure to a mixture of pesticides in epidemiological investigations. PMID- 8010300 TI - Mortality from respiratory cancers (including lung cancer) among workers employed in formaldehyde industries. AB - A joint study on effects of formaldehyde exposure in industrial populations by the National Cancer Institute and the Formaldehyde Institute, Inc. (Blair et al. [1986]: J Natl Cancer Inst 76: 1071-1084; Blair and Stewart [1989]: J Occup Med 31: 881, Blair et al. [1990]: Am J Ind Med 17:683-700) reported no significant elevation in risk ratios standardized to the general population. Using the same data as Blair et al., we compared more exposed to less exposed workers to compute relative risk for respiratory and lung cancers using a multivariate, log-linear model incorporating factors for job type (hourly vs. salaried), cumulative exposure (0.1-0.5, 0.5-2, 2+ vs. < 0.1 ppm/years), length of exposure (1-5, 5-10, 10+ vs. < 1 years), and age. Models were fit for all workers, all males, all workers less than 65 years of age, and for all males less than 65 years of age. Hourly workers have a significantly elevated relative risk when compared to salaried workers. While only high levels of cumulative exposure show a significant elevation in relative lung cancer risk, trend analyses of the coefficients of a log-linear model show a significant trend of increasing risk with increasing formaldehyde exposure. The significantly elevated respiratory and lung cancer risk for workers younger than 65 may indicate a shift of respiratory cancer mortality towards younger ages among those occupationally exposed to formaldehyde.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8010301 TI - Occupations associated with low offspring sex ratios. PMID- 8010302 TI - Potency versus importance in fiber pathogenicity. PMID- 8010303 TI - Fiber potency vs. importance. PMID- 8010304 TI - Reproductive autonomy and evolutionary biology: a regulatory framework for trait selection technologies. AB - The Constitution protects, in some measure, each person's autonomy in making basic decisions about family, parenthood, and procreation. This Article examines the extent to which courts should protect from government intrusions a parent's access to technologies that influence specific characteristics of offspring. Beginning with Supreme Court opinions that articulate constitutional and social values regarding reproductive autonomy, the Article explores how important new insights from evolutionary biology may supplement an understanding of human procreation. Specifically, the Article explains how trait selection can constitute an important part of larger "reproductive strategies" that powerfully affect an individual's "inclusive fitness" (itself a measure of reproductive success). It concludes that access to trait-selection technologies should receive the same federal protection from government intrusions as that afforded access to abortion. It proposes the first limit to that protection, however, when a parent seeks to select for a trait, or to use a technique, that would be clearly and significantly damaging to the future child. The Article subsequently divides the use of trait-selection technologies (TSTs) into eight contexts and proposes a preliminary framework by which a regulatory system could legitimately distinguish among them. PMID- 8010305 TI - Elder choice. AB - Thanks to medical technology, thousands of elderly patients suffer the agony of debility, from which many of them would choose to be released if they knew how to effect a choice. Prolonging their metabolism is unfair to them and to their families, and strains the nation's overburdened health care resources. Medical directives offer elderly patients avenues of escape from unwanted treatment. Health care for the aged should include informed access to these means of choice. PMID- 8010307 TI - Who's monitoring the quality of mammograms? The Mammography Quality Standards Act of 1992 could finally provide the answer. AB - Breast cancer remains a leading cause of death among American women, yet little is known about its etiology and prevention. Screening mammography is currently the best preventative measure available to women, but comprehensive oversight of this procedure is necessary in order to minimize and, ultimately, eliminate "errors" that compromise quality and accuracy and give too many women a false sense of security. This Note describes our nation's battle against breast cancer, emphasizes the need for uniform, mandatory quality and safety standards for screening mammography, and outlines The Mammography Quality Standards Act of 1992, which seeks to provide the framework necessary to implement such standards and restore the preventative power of this procedure. This Note analyzes the terms of the Act and concludes that the Act could provide women with the true sense of security that has eluded so many women-too many women-for so long. PMID- 8010306 TI - A tale of three women: a survey of the rights and responsibilities of unmarried women who conceive by alternative insemination and a model for legislative reform. AB - Courts in a number of jurisdictions have recently confronted questions of legal parentage concerning children conceived by alternative insemination. Typically, the biological mother is contesting the right of either the sperm donor or a non biological co-parent to custody or visitation. This Note surveys the current state of the law and demonstrates a lack of protection for the rights of unmarried biological mothers and their co-parents. This Note then proposes a new paradigm for establishing the parties' rights and obligations, one that reflects the parties' pre-insemination, mutual intent regarding parenting responsibilities and encourages legal acknowledgement of and protection for the families people are creating with the help of AI. PMID- 8010308 TI - Federal panel updates recommendations on cholesterol management. National Heart, Lung, and Blood Institute. PMID- 8010309 TI - Not enough health professionals advise smokers to quit, says CDC. PMID- 8010310 TI - CDC reports death rate trends for smoking-related cancers: lung cancer leads the pack. PMID- 8010311 TI - Kudzu extract shows potential for moderating alcohol abuse. PMID- 8010312 TI - Weathering reviews by outside consultants in the era of patient-focused care. PMID- 8010313 TI - The measurement mandate: report card day is coming. PMID- 8010315 TI - Pharmacist-managed medication review in a managed care system. AB - A medication-review service at a managed care facility was studied. The service, developed in 1991, provides in-depth analysis of medication use and patient consultation by a pharmacist. Patients are seen by referral. During a visit, the pharmacist reviews each medication for patterns of use, clinical response, and adverse effects and if necessary teaches the patient how to use the drugs more appropriately. The pharmacist may change some aspect of the prescription and may schedule follow-up visits. The investigators reviewed data on (1) medication related problems for all new patients seen by the pharmacist during the first 12 months of the service, (2) patient demographics for the first 23 months, (3) utilization of the service and pharmacist productivity for the first 23 months, (4) utilization of medications and health care services in a representative subset of patients 12 months before and after they used the service, and (5) costs. A total of 2720 medications were reviewed during months 1-12. On average, 64.9% of the drugs reviewed each month were problematic. A total of 836 patients were seen during the first 23 months; most of the referrals were from physicians. The patients averaged 2.6 diagnoses and 4.7 drugs each and were not dominated by any one age group, gender, diagnosis, or drug therapy. A representative subgroup showed reductions in the number of unscheduled physician visits, urgent care visits, emergency room visits, and hospital days; a savings of $644 per patient per year was calculated. Patients used fewer health services during the year after they began participating in a pharmacist-managed medication-review program. PMID- 8010314 TI - Oral ondansetron for preventing nausea and vomiting. AB - Available clinical data on the use of oral ondansetron for the prevention of nausea and vomiting in patients undergoing cancer chemotherapy or surgery are reviewed. Injectable ondansetron hydrochloride is very effective in preventing nausea and vomiting associated with even the most emetogenic antineoplastic drugs. In December 1992, 4- and 8-mg oral tablets (ondansetron hydrochloride dihydrate) became available. Many of the clinical trials of oral ondansetron have not compared it with other antiemetics or have compared it only with placebo. Oral ondansetron has shown efficacy in such trials, but the standard of care for preventing chemotherapy-induced emesis is not placebo. Studies involving a prechemotherapy i.v. dose of ondansetron followed by oral therapy have shown high response rates for the whole study period; however, when day 1 is excluded, the results are not impressive for the remainder of the study period. It seems that the period beyond 24 hours is when oral ondansetron is effective, and that efficacy against acute emesis is due to i.v. ondansetron. Clinical trials in which oral ondansetron and oral metoclopramide were compared showed ondansetron to be, at best, equal to metoclopramide. One study showed the combination of dexamethasone and metoclopramide to be superior to oral ondansetron. Oral ondansetron is more effective than placebo in preventing post-operative nausea and vomiting in gynecologic surgery patients; however, there have been no comparative studies, and routine use of antiemetics in most surgical patients may be unnecessary because newer anesthetics are less emetogenic. Although the adverse effects of oral ondansetron are milder than those of standard antiemetics, this may not compensate for the drug's high cost. Oral ondansetron is not superior to traditional antiemetics for the prevention of nausea and vomiting caused by chemotherapy or surgery. PMID- 8010316 TI - Effect of a clinical psychopharmacy consultation service on patient outcomes. AB - The effect of a psychopharmacy consultation service on outcomes in patients with psychiatric disorders was studied. The medical records of 30 randomly selected patients who had been hospitalized between August 1990 and July 1992 at a private psychiatric institution and who had been seen by the psychopharmacy consultation service during that period were reviewed. Data obtained included (1) patient demographics, (2) patient information generated by the psychopharmacy consultation, (3) the types of recommendations made by the psychopharmacy specialist and whether the recommendations were accepted by the physician, and (4) the clinical outcome. Forty-three psychopharmacy consultations for the 30 patients were evaluated. A total of 125 recommendations were made by the consultation service; of these, 75 (60%) were accepted. The consultations were divided into consultations for which at least a majority of the resulting recommendations were accepted by the physician (n = 29) and consultations for which less than a majority of the recommendations were accepted (n = 14). For the majority group, 23 (79%) of the 29 consultations were associated with a positive outcome, compared with 2 (14%) of the 14 consultations in the less-than-majority group. Similarly, positive outcomes were significantly more frequent in the majority-group patients (16/21 [76%]) than in the less-than-majority-group patients (2/9 [22%]). The frequency of positive outcomes was higher among patients for whom most of the recommendations of a clinical psychopharmacy consultation service were accepted than among patients for whom most recommendations were not accepted. PMID- 8010317 TI - Benefits and work-schedule options in hospital pharmacy practice. AB - Hospital pharmacy directors were surveyed to determine whether their departments offered specific family-related benefits and work-schedule options and how their attitudes about these options compared with those of female hospital pharmacists. Questionnaires were mailed to 300 randomly selected hospital pharmacy directors to collect the following information: vacancy rates and male:female ratios in hospital pharmacy positions, which of 13 selected benefits and work-schedule options were offered, barriers that prevented the other options from being offered, and attitudes about the listed options. The options included in the survey were selected because they represent ways of balancing home and work (e.g., maternity leave, job sharing, day care). The pharmacy directors' responses were compared with those from a similar survey of female hospital pharmacists. The usable response rate was 50.3%. Position vacancy rates ranged from 5.5% for directors to 35.8% for clinical supervisors. All full-time positions had an even distribution of men and women except for director and assistant or associate director positions. Of 13 options, only maternity leave, part-time schedules, and flexible schedules were offered by more than half of the hospitals. These three were also the only listed options that the respondents considered important in recruiting and retaining pharmacists. Barriers to offering other options included the perception that current benefits and work-schedule options were adequate, lack of staff coverage, lack of funds, and the perception that some positions are not compatible with alternative schedules. Respondents' ratings of the importance of the listed benefits and work-schedule options were significantly lower than ratings given by female hospital pharmacists in a separate survey.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8010319 TI - Vancomycin pharmacokinetics in middle-aged and elderly men. AB - A study was conducted to establish new values for vancomycin volume of distribution (V) and clearance (CL) that would result in more accurate predictions of serum vancomycin concentrations (SVCs). All patients who had received vancomycin at a Veterans Affairs medical center were divided into two groups: those for whom SVCs had been measured between August 13, 1990, and February 12, 1991 (group 1), and those for whom SVCs had been measured between February 13, 1991, and October 4, 1991 (group 2). Data for group 1 were used to derive new values for V and CL by means of Bayesian analysis. SVCs for each patient in group 2 were calculated by using the new pharmacokinetic values, and the predictive performance of these values was compared with that of accepted population values (V = 0.70 L/kg, CL = 0.65 times creatinine clearance [CLcr]). Forty-four men with 95 SVCs were entered into group 1, and 69 men with 171 SVCs were entered into group 2. The mean +/- S.D. ages for groups 1 and 2 were 61.6 +/ 12.9 and 64.3 +/- 11.3 years, respectively. There were no significant differences between the groups. V could not be evaluated because of inadequate sample size. Compared with the method employing the conventional CL value, the method that assumed a CL of 0.90CLcr was more precise and less biased in estimating group 2 SVCs. In middle-aged and elderly men, use of a CL value of 0.90CLcr produced estimates of serum vancomycin concentration that were more precise and less biased than did use of a CL value of 0.65CLcr. PMID- 8010318 TI - Benefits and work-schedule options for female hospital pharmacists. AB - Female hospital pharmacists were surveyed to determine what benefits and work schedule options they want and how they feel about those currently offered. Questionnaires were mailed to 750 randomly selected female ASHP members to (1) collect employment and personal data, (2) determine which of 13 family-related benefits and work-schedule options were offered at their institutions, (3) assess use of and attitudes about these options, and (4) determine whether use and attitudes differ by position or parental status. The options included in the survey were selected because they represent ways of balancing home and work (e.g., job sharing, day care, parental leave). The usable response rate was 65.3%. About 59% were married and 40% had children. Most (83.3%) held full-time positions, and 36.5% held staff nonclinical positions. More than 70% of the respondents indicated that a flexible schedule, flextime, and maternity leave were important in combining personal and professional roles. Respondents indicated that many of the benefits and work-schedule options that were not routinely offered would be used to a great extent if offered. Forty percent reported satisfaction with current benefits and work-schedule options. Many surveyed female ASHP members considered their current benefits and work-schedule options less than optimal and would be interested in more flexible schedules and benefits. PMID- 8010320 TI - Immune globulin use at a multihospital medical center. AB - Use of i.v. immune globulin (IVIG) at four hospitals was audited to evaluate the need for therapeutic protocols and identify strategies for reducing drug expenditures. Charts and nursing notes for patients who received IVIG over a six month period were reviewed retrospectively to obtain the following data: patient demographics, indication for IVIG use, product used, amount administered, and adverse reactions. Indications were categorized as to whether they are included in FDA-approved labeling, recognized in national guidelines, documented in published studies, or not documented. Expenditures were calculated from acquisition costs. At the first hospital (which offers oncology and other specialty services for adult patients), 71 patients received IVIG for 15 indications, with 89.5% of the orders for unlabeled uses. Of all grams reconstituted, 17.8% were wasted. The rate of documented adverse reactions was 11.3%. At the second, a pediatric hospital, 34 patients received IVIG for six indications, with 65% of the orders for unlabeled uses. Of all grams reconstituted, 13% were wasted. At the third hospital (which specializes in emergency trauma and critical care medicine), two patients received IVIG for a labeled indication. At the fourth (a maternity hospital), no patients received IVIG. Three of four hospitals used IVIG during a six-month audit period. In most instances, the drug was used for indications not included in FDA-approved labeling. Audit information may be useful in creating guidelines for appropriate use of IVIG. PMID- 8010321 TI - Stability of ondansetron hydrochloride in syrups compounded from tablets. PMID- 8010322 TI - Stability of cefuroxime sodium and aminophylline or theophylline. PMID- 8010323 TI - Visual compatibility of fentanyl citrate with selected drugs during simulated Y site injection. PMID- 8010324 TI - Development of a successful research grant application. AB - The process of identifying appropriate funding agencies for research projects is described, and grant application and review procedures are explained. Although the federal government is the largest single source of research funding, financial support is also offered by associations, foundations, and corporations. Research funding may be divided into two major types: grants, which are awarded in response to investigator-initiated projects, and contracts, under which the research topic is proposed by the funding agency. Competing successfully for grants and contracts requires a sound research plan whose objectives are consistent with those of the funder. Identification of an appropriate potential funding agency requires familiarity with its areas of interest, the size of grants offered, and other criteria. The development of the grant application has several steps, including determining specific aims and long-term project goals, reviewing the literature, obtaining letters of consent from collaborators and consultants, securing colleagues' assistance in reviewing the drafts, preparing a budget, and drafting and revising the proposal. Most grant applications have a number of common elements; each funder also may have unique requirements. Authors should familiarize themselves with the application criteria of the agency or institution from which they are seeking support and follow them scrupulously. Competition for grant funds is high, and many worthwhile proposals are rejected. After studying the reviewers' comments, the author may wish to revise the application for resubmission or submission to a different funding agency. Sound planning, selection of an appropriate funding agency, and preparation of a well written proposal play key roles in successful grantsmanship. PMID- 8010325 TI - Protecting hospital employees and visitors from aerosolized ribavirin. PMID- 8010326 TI - Criteria for use of paroxetine hydrochloride in adult inpatients and outpatients. American Society of Hospital Pharmacists. PMID- 8010327 TI - Patients not receiving a drug deserve our attention, too. PMID- 8010328 TI - Continuing problem of ciprofloxacin administered with interacting drugs. PMID- 8010329 TI - Preventing medication errors in antineoplastic therapy. PMID- 8010330 TI - Upcoming public service campaign on medication use. PMID- 8010331 TI - Presentation of the Southern Society for Clinical Investigation Founder's Medal to Dr. Andrew H. Kang. PMID- 8010332 TI - Lack of effects of beta-carotene on lipids and sex steroid hormones in hyperlipidemics. AB - Beta-carotene in doses of up to 300 mg daily raises high-density lipoprotein cholesterol levels within 2 to 4 weeks in healthy subjects. The authors, in this study, investigate the short-term effects of high-dose beta-carotene upon serum lipids, lipoproteins, and selected sex steroid hormones in 59 adult patients with Type IIa or IIb hyperlipidemia and 36 healthy subjects. Volunteers took beta carotene (300 mg) or wheat germ oil capsules daily for 30 days. Lipids were measured on days 1, 14, 21, and 30. Beta-carotene, retinol, free and total testosterone, and estradiol levels were measured on days 1 and 30. Total high density lipoprotein cholesterol levels increased 10% (p < 0.01) over baseline in all groups by day 14 but returned to baseline by day 30. Total cholesterol, low density lipoprotein cholesterol, and triglyceride levels transiently increased between days 14 and 21 by up to 9%, 8%, and 20%, respectively, only in the patients with hyperlipidemia treated with beta-carotene, but returned to baseline on day 30. Apolipoproteins A and B were unchanged. Despite 20-fold increases of plasma beta-carotene levels there, were no reports of carotenodermia and no alteration in sex steroid hormones, retinol levels, hepatic transaminases, or persistent changes in serum lipids that were attributable to beta-carotene. PMID- 8010333 TI - The effect of esophageal mechanical and chemical stimuli on salivary mucin secretion in healthy individuals. AB - Because of a newly developed model of esophageal perfusion in humans, the authors could study the role of esophago-salivary reflex in salivary neutral and acidic mucin output. The basal rate of neutral mucin output was 0.24 +/- 0.06 mg per minute. Placement of intraesophageal tubing and inflation of balloons resulted in a highly significant increase in salivary mucin output (2.10 +/- 0.22 mg per minute; p < 0.00001). However, implementation of esophageal perfusion with saline resulted in a significant decline of salivary mucin output (1.28 +/- 0.10 mg/mL NaCl4 versus 2.08 +/- 0.24 mg/mL NaCl1; p < 0.001). Esophageal perfusion with hydrochloric acid prevented the decline of salivary mucin output observed during perfusion with saline, whereas infusion of hydrochloric acid/pepsin resulted in a significant enhancement of salivary mucin output (2.89 +/- 0.31 mg per minute; p < 0.01). Therefore, mechanical and chemical stimulations resulted in an overall 9 fold and 12-fold increase in the rate of salivary mucin output over the basal value, respectively. The basal rate of acidic mucin secretion was 0.26 +/- 0.06 mg per minute. After placement of intraesophageal tubing, inflation of balloons, perfusion hydrochloric acid, or hydrochloric acid-pepsin solution, a significant enhancement in the rate of salivary acidic mucin output, similar to that observed during measurement of neutral mucin, was observed. Therefore, during mechanical and chemical stimulation, the rate of salivary acidic mucin output increased 7.3 fold and 11.1-fold over the basal value, respectively.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8010334 TI - An alternative approach to smoking control. AB - The detrimental health effects of cigarette smoking, including the increased risk of cancer, cardiovascular disorders, and pulmonary diseases, are well established. Although most smokers express a desire to quit, 46 million Americans continue to smoke because of the nicotine addiction associated with the habit. The author, in this paper, describes the magnitude of the health risks related to various forms of tobacco use and proposes that smokeless tobacco be recommended as a cigarette substitute by persons who cannot stop smoking. This proposal is made because smokeless tobacco is associated with far fewer and considerably less serious health consequences than is smoking. Of primary concern is oral cancer, the annual incidence of which is estimated at 26 cases per 100,000 smokeless tobacco users. If all American smokers used smokeless tobacco instead, this would result in 12,000 cases of oral cancer per year. This is only 1/20 of all smoking related cancers, less than 1/10 of smoking-related lung cancers, and less than half the number of oral cancers now attributed to smoking. A public health policy that recognizes smokeless tobacco as an alternative to smoking would benefit individuals confronted with the unsatisfactory options of abstinence or continuing to smoke. PMID- 8010335 TI - Case report: postpartum hypopituitarism in a patient with sickle cell trait. AB - The authors report a case of hypopituitarism in a 28-year-old woman who appeared to develop this in conjunction with a pregnancy 4 years previously. The patient had clear-cut evidence of secondary hypoadrenalism and secondary hypothyroidism. A magnetic resonance imaging scan revealed a partially empty sella of normal size. The patient had no prior evidence of peripartum hypotension or other obstetrical catastrophe. Her only recognizable risk factor was the presence of sickle cell trait. The authors speculate that her sickle trait predisposed her to develop pituitary infarction during her first pregnancy. The authors also review three previous cases linking sickle cell syndromes with hypopituitarism and suggest that this case further supports the concept that sickle cell syndromes can predispose affected individuals to pituitary infarction and ultimately to subsequent hypopituitarism. PMID- 8010336 TI - Positive response to oral divalproex sodium (Depakote) in patients with spasticity and pain. AB - Divalproex sodium (DVS; Depakote) is a commonly used antiepileptic agent that increases the levels of gamma aminobutyric acid. Spasticity from different causes may be due to a deficiency of inhibitory transmitters like gamma aminobutyric acid or an excess of excitatory neurotransmitters. Spasticity also may be accompanied by pain. The authors administered DVS orally for pain and spasticity in three patients with a history of spinal cord injury and one patient with a history of head injury. Three patients had marked improvement in spasticity and pain. One patient, who had some symptomatic improvement in spasticity, could not tolerate DVS because of gastric irritation. In contrast to the side effects of sedation and increased motor weakness associated with antispasticity drugs commonly used, no such side effects were detected with DVS. It is suggested that a possible enhancement by DVS of gamma aminobutyric acid-ergic postsynaptic inhibition of motor reflex arc in the spinal cord may represent a new nonsedating, management approach for spasticity as a result of traumatic spinal cord and head injuries. PMID- 8010337 TI - Perioperative myocardial infarction with noncardiac surgery. AB - The incidence of perioperative myocardial infarction with noncardiac surgery varies by the type of procedure and the prevalence of coronary atherosclerosis in the study population. Incidence is < or = 1% with minor procedures and may exceed 10% with vascular operations. The case fatality rate continues to be 30% to 50%. Pathogenesis is not understood completely. Diagnosis is sometimes problematic, because less than 50% of patients complain of chest pain. In addition, a high frequency of notable but apparently innocent postoperative electrocardiograph changes limits the diagnostic use of the electrocardiogram. Fortunately, the creatine kinase MB isoenzyme retains its sensitivity and specificity for acute infarction in perioperative patients. Different approaches to preoperative risk assessment have been developed, including a summative cardiac risk index and a stratification system based on the likelihood that the most powerful risk factor (coronary artery disease) is present. Although many interventions have been recommended to lower perceived risk, none has been tested in a randomized controlled trial, and their comparative efficacy and safety is unknown. PMID- 8010338 TI - Coffee: brew or bane? AB - Coffee is the most commonly used drug in the United States. The medical literature is conflicted regarding the harmful effects of coffee and caffeine. Because the articles that have appeared are so different, a formal meta-analysis is not the ideal way to summarize the data. However, this literature review suggests that coffee does not have an appreciable effect on hyperlipidemia, hypertension, ischemic heart disease, or cancer. The effects of decaffeinated coffee are much less well-defined, and there is little rationale for recommending that patients switch to decaffeinated coffee. A less appreciated problem with caffeine is that it may increase the risk of osteoporosis and hip fracture. PMID- 8010339 TI - Clinical experience with atovaquone: a new drug for treating Pneumocystis carinii pneumonia. AB - Atovaquone is a new hydroxynapthoquinone antiprotozoal agent active against Pneumocystis carinii in vitro and in animal models. The authors report an experience using atovaquone to treat 25 patients with mild to moderate P. carinii pneumonia. Eligible patients were treated for 21 days with 750 mg of atovaquone orally three times daily. Prednisone was added when the P(A-a)O2 gradient was between 35-45 mm Hg. Patients were treated under three treatment protocols. Patients in Group 1 participated in one of two randomized comparative drug trials, designed for patients with and without sulfonamide intolerance. Six of seven patients successfully completed treatment, and one patient discontinued treatment because of an adverse reaction (> 5 times baseline increase in transaminase level). Patients in Group 2 were treated with atovaquone for mild to moderate P. carinii pneumonia under a treatment Investigational New Drug protocol because of prior sulfonamide reactions. Fifteen of these 18 patients successfully completed treatment; one died from other complications during treatment and two discontinued treatment for adverse reactions (> 5 times baseline increase in transaminase levels, and a diffuse rash). Serum transaminase levels returned to normal at the end of treatment in all patients with elevated levels. All patients demonstrated clinical resolution of their pneumonia and improvement of pretreatment hypoxemia (Group 1: pretreatment PaO2 = 82 +/- 14 mm Hg, posttreatment PaO2 = 92 +/- 9 mm Hg). Overall, 21 (84%) of 25 patients successfully finished therapy without significant adverse reactions. Atovaquone appears to be an effective and well-tolerated oral treatment for mild to moderate P. carinii pneumonia.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8010340 TI - Uses of clinical databases. AB - Clinical databases consist of observational data collected on patients who meet specific criteria. The uses of these databases depend on whether the observations are drawn from a single institution, multiple clinical centers, or are population based. Single institution databases frequently are used to profile patient accrual. In cases of rare diseases or unusual procedures, multicenter databases are required to amass sufficient information for study. Multicenter databases can be used to address issues related to intercenter variation and to develop statistical models to predict outcome based on prognostic factors. Population based databases are required to assess incidence, prevalence, and mortality rates of disease. Although the inferences that can be drawn from observational data are limited by selection bias, clinical databases are valuable tools in planning clinical research. Clearly, however, resources are required to develop and maintain clinical databases. In an era when much research funding is directed at hypothesis-driven research, the importance of these clinical databases in developing clinical research hypotheses should not be overlooked. PMID- 8010341 TI - Southwestern Internal Medicine Conference: postmenopausal estrogen supplementation: a cardiologist's perspective. AB - Women live nearly one third of their lives after ovarian function has ceased. The implications of menopause for both health and disease as well as the risks and benefits of hormonal replacement therapy are important considerations in the management of postmenopausal women. The author discusses the relation between menopause and coronary heart disease (CHD) risk and evaluates the risks and benefits of hormonal replacement therapy from a cardiologist's perspective. During menopause, there are changes in the lipid profile that favor the development of CHD. In addition, there is convincing evidence that the risk of CHD increases with surgical menopause and that natural menopause also may signal a period of increasing risk. Data from angiographic and prospective studies suggest that a reduction in CHD risk is associated with estrogen use in postmenopausal women and that a large part of the beneficial effect of estrogen on CHD risk is through changes in the lipid profile. The benefit of hormonal replacement therapy for reduced risk of CHD, however, must be viewed in the setting of the overall risks and benefits of hormonal replacement therapy for each individual patient. PMID- 8010342 TI - Implications of the anemia of chronic disorders in patients anticipating radiotherapy. AB - The authors assess prevalence of anemia in a population of patients anticipating radiation therapy. They also characterize the anemia and determine its relationship to stage, inflammation, and mortality. Blood counts were recorded for 81 of 103 patients surveyed during August 1988. When available, iron studies were used to characterize anemia. Stage, treatment, and 3-year mortality were obtained from tumor registry data. Many patients had anemia of chronic disorders. Therefore, 16 adults with solid tumors anticipating radiation therapy were evaluated with complete blood counts, iron studies, chemistries, erythropoietin, and measures of inflammation. Of 81 patients, more than half were anemic. Thirteen of 17 patients with anemia and with iron studies had anemia of chronic disorders. Two-thirds of patients with anemia had advanced cancer, versus one third of patients without anemia. Twice as many patients with anemia compared with those without anemia died within 3 years. Of 16 patients studied intensively, 4 had anemia, advanced cancer, and died within 6 months, whereas all 12 patients without anemia lived longer. The 4 patients with anemia had an elevated iron index (7.95), erythrocyte sedimentation rate (86 mm per hour), and C-reactive protein (4.48 mg/dL) versus those of 12 patients without anemia and 10 volunteers. Erythropoietin levels were not different significantly among groups. Anemia indicated a poor prognosis during and before radiotherapy, and anemia of chronic disorders was associated with advanced cancer and a short survival rate. PMID- 8010343 TI - Deletions of Xq and growth deficit: a review. AB - A critical review of the literature disclosed 44 cases with a 46,X,Xq- karyotype without apparent mosaicism. Of these, 17 were of normal height (compared to the respective population), 11 had a height of over 1 SD below the mean, and 16 had a height of over 2 SD below the mean with breakpoints between Xq13 and Xq25. Since patients of normal height occurred with breakpoints as proximal as Xq13 we conclude that there is no major "growth gene" on Xq distal to q13. The most likely explanation for the variable phenotypic effect of Xq- is to assume that growth gene(s) in Xp or proximal Xq are inactivated on such a chromosome with some variability similar to the variable spreading of X inactivation seen in some X-autosome translocations. PMID- 8010344 TI - Wisconsin Stillbirth Service Program. PMID- 8010346 TI - Wisconsin Stillbirth Service Program: II. Analysis of diagnoses and diagnostic categories in the first 1,000 referrals. AB - The Wisconsin Stillbirth Service Program has provided a mechanism for the collection and analysis of unbiased and representative information concerning stillborn infants. Generated diagnoses and diagnostic categories within the first 1,000 referrals (including 789 stillbirths) is summarized here. Among all referred stillborns, 24.5% were found to have an identifiable intrinsic fetal cause of death. Specific diagnoses were extraordinarily heterogeneous, with about 85 different processes identified with this group. No single diagnosis was found in more than 1 1/2% of the evaluated stillborns. Distribution by classes of fetal causes (as a percent of all fetal causes in stillborns) included malformation syndromes in 44%, single malformations and defined sequences in 34%, disruptions in 10%, and dysplasias in 3%. The heterogeneity of syndromic causes is illustrated, examples of previously undescribed syndromic processes provided and the problems experienced in generating specific diagnoses discussed. Specific single malformations, sequences, disruptions, and dysplasias are also tabulated and illustrated. Distribution by etiologic categories (as a percent of all fetal causes in stillborns) included defined sporadic conditions in 29%, cytogenetic aberration in 25%, presumed multifactorial processes in 12%, Mendelian disorders in 5%, and environmental events in less than 4%. A fourth of all fetal causes could not be sufficiently defined to allow for certainty in assigning a specific etiologic category. The materials summarized provide reference data regarding the frequency of classes and categories of fetal diagnoses generated from an unbiased and non-selected series of stillborns. PMID- 8010345 TI - Wisconsin Stillbirth Service Program: I. Establishment and assessment of a community-based program for etiologic investigation of intrauterine deaths. AB - Although stillbirth is a common event, few programs have previously been established for the comprehensive etiologic investigation of intrauterine death. Fewer still have been prospective, unbiased in ascertainment, and consistent in protocol utilization. The Wisconsin Stillbirth Service Program was established in 1983 as a unique model for the investigation of the causes of stillbirth. This community-based, University-supported model for health care delivery is here described. Through it more than a thousand infants have been etiologically investigated. We demonstrate that a community-based program of stillbirth assessment can succeed, that compliance with recommended protocols is high and that a specific primary cause of fetal death can be demonstrated in about 40% of referrals. A majority of the established causes of intrauterine death are fetal etiologies. Furthermore, it appears that there are no substantial referral biases. Lack of such biases, together with the prospective, protocol driven nature of the program provides a unique population upon which to base estimates of the frequency of various etiologic diagnoses and classes and categories of cause. PMID- 8010347 TI - Lower mesodermal defects: a common cause of fetal and early neonatal death. AB - Among the first 1,130 referrals to the Wisconsin Stillbirth Service Program 17 infants have been recognized to share phenotypic characteristics involving the genital, urinary, lower gastrointestinal, and axial skeletal systems. The pattern of abnormalities identified appears to be limited to structures sharing a common embryologic origin. These features, for the most part, are shown to be non randomly associated. No clearly definable sub-groups within this population are demonstrable. The pattern of abnormalities is defined to include abnormalities of the following structures as pathogenetically primary features: lumbosacral vertebrae, kidneys, ureters, uterus/fallopian tubes, vagina, bladder, urethra, adrenals, gonads, anorectum, external genitalia, and umbilical arteries. An embryologic mechanism is proposed which explains this non-random association as arising secondary to disruption of structures derived from the lower portion of the primitive intraembryonic mesoderm. The Lower Mesodermal Defects Sequence appears to be a rather common (and under-recognized) cause of stillbirth and immediate neonatal death. PMID- 8010348 TI - Fallot complex, severe mental, and growth retardation: a new autosomal recessive syndrome? AB - We report on the syndromic occurrence of the Fallot complex in sibs born to consanguineous Pakistani parents. Additional manifestations included minor facial anomalies, pronounced failure to thrive, and mental retardation. Expression of the syndrome varied. While one of the four patients had cardiac malformations, another sib had only non-cardiac manifestations. The clinical findings suggest a new autosomal recessive syndrome. PMID- 8010349 TI - Further delineation of pseudotrisomy 13 syndrome: a case without polydactyly. AB - We report on a baby with holoprosencephaly, median cleft lip, cardiac and genital anomalies, normal upper limbs, and a 46,XX karyotype. We also reviewed 22 karyotypically normal cases whose clinical features resembled trisomy 13 syndrome and compared them with the case we present. The problem of variable expression of the pseudotrisomy 13 syndrome versus genetic heterogeneity is illustrated. PMID- 8010350 TI - Sexing of human embryos and fetuses by fluorescent in situ hybridization (FISH) to paraffin-embedded tissues with sex chromosome-specific DNA probes. AB - A fluorescent in situ hybridization (FISH) study was carried out on paraffin sections of human embryonic and fetal tissues with two DNA probes, DXZ1 and DYZ1 (Oncor), for X and Y chromosome-specific DNA sequences, respectively. The specificity of the DNA probes was confirmed on metaphase and interphase lymphocytes of healthy normal adult males. The paraffin blocks of the human embryonic and fetal tissues examined in the present study had been stored at room temperature for up to 5 years after fixation in 4% paraformaldehyde. All the seven embryos and five fetuses examined were successfully sexed by FISH. The cells from three embryos and four fetuses were positive for a hybridization signal with each of the DXZ1 and DYZ1 probes and they were classified as male. The cells from the remaining four embryos and one fetus were positive for two identical hybridization signals with the DXZ1 probe in a nucleus instead of the absence of the signal hybridized with DYZ1, indicating that their cells have two X chromosomes but no Y chromosomes. The FISH results for the five fetuses examined were consistent with their genital sex and/or gonadal histology. The FISH results were highly specific and no false positive or false negative results were obtained. Thus, the FISH technique has been shown to visualize specific DNAs in situ on paraffin sections and to be useful to determine the sex of fixed embryos and fetuses retrospectively. PMID- 8010351 TI - Cognitive functioning and information processing of adult mentally retarded men with fragile-X syndrome. AB - The present study describes cognitive skills and information processing strategies of mentally retarded fra(X) men. Fifty-eight fra(X) positive and 58 fra(X) negative adults, matched on sex, chronological age, length of institutionalisation, general cognitive level, and living conditions, were evaluated with the Bayley or McCarthy Scales of Mental Abilities. Mental ages were mostly situated in the severe mental handicap category and were found to be negatively influenced by chronological age. A relative strength in perceptual performance and non-verbal reasoning and a deficit in sequential information processing turned out to be typical of all mentally retarded subjects, irrespective of fra(X) or control status. Fra(X) adults could be significantly differentiated from control persons on the ground of a higher level of acquired knowledge because of better vocabulary and verbal-expressive skills. On the other hand, they were less able to imitate non-verbal patterns, had more difficulty with visual-motor integration and co-ordination, and applied less efficient general mental processing skills in solving new problems. The memory profile of fra(X) adults was strongly determined by the meaning and the complexity of the information that has to be reproduced. In this article the profile of cognitive strengths and weaknesses in the fra(X) group will be discussed and some general advice for training is suggested. PMID- 8010352 TI - Vohwinkel syndrome (mutilating keratoderma) associated with craniofacial anomalies. AB - We describe a female patient with Vohwinkel syndrome (mutilating palmoplantar keratoderma), who in addition showed cleft lip and palate, microcephaly, facial asymmetry, and other anomalies. PMID- 8010353 TI - Multiple malformations in neonatal hemochromatosis. PMID- 8010355 TI - Prevalence and incidence of major depression in Alzheimer's disease. AB - OBJECTIVE: This study examined the prevalence and incidence of major depressive disorder in Alzheimer's disease. METHOD: The authors retrospectively reviewed two large Alzheimer's disease databases, one at the University of Texas Southwestern Medical Center in Dallas and the other at the Consortium to Establish a Registry for Alzheimer's Disease (CERAD). The Dallas series contained 264 cases of Alzheimer's disease, of which 153 patients were followed up for an average of 3 years from initial evaluation. The CERAD database contained 1,095 cases and excluded patients with histories of depression at initial evaluation; 325 of these patients were followed up for at least 2 years. Alzheimer's disease was diagnosed according to the criteria of the National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer's Disease and Related Disorders Association; major depression was diagnosed according to the DSM-III-R criteria. Most of the patients in these series were dwelling in the community and had had Alzheimer's disease symptoms for approximately 4 years at the time of evaluation. RESULTS: In the Dallas series there was a 1.5% prevalence and a 0% incidence of major depression. In the CERAD series there was a 1.3% 2-year incidence of major depression. CONCLUSIONS: The low prevalence and incidence of DSM-III-R major depression in these patients suggest that for the period of time the patients were followed up, Alzheimer's disease did not predispose to major depression. However, major depression may herald the subsequent onset of dementia. Depression in dementia should perhaps be diagnosed by different criteria. PMID- 8010354 TI - Expressed emotion, perceived criticism, and relapse in depression: a replication in an Egyptian community. AB - OBJECTIVE: The aims of this study were to determine the value of families' expressed emotion and patients' perception of family criticism in predicting relapse in Egyptian depressed patients and to evaluate transcultural differences in assessment of these measures. METHOD: The subjects were 32 consecutive depressed patients from psychiatric clinics in Cairo and Ismailia, Egypt, who fulfilled the DSM-III-R criteria for major depression or bipolar disorder. An Arabic version of the Camberwell Family Interview was administered to key relatives of the depressed patients. Rating of expressed emotion was performed blindly by a qualified rater to assess levels of criticism, hostility, emotional overinvolvement, warmth, and positive remarks. Patient perception of family criticism (perceived criticism) was also assessed. All patients were followed up for 9 months to assess relapse and compliance with treatment. RESULTS: The relation of family criticism to relapse was statistically significant. Although this result replicates previous findings, the criticism level that best differentiated relapsers and nonrelapsers was a score of 7, which is much higher than previously reported in Western studies. This relation was not observed for other expressed emotion components. Also, no association between perceived criticism and relapse was detected. CONCLUSIONS: Expressed emotion is a prognostic factor that should be assessed with consideration of the specific culture and intrafamilial patterns. The use of perceived criticism in the prediction of relapse in depression is questionable. There is a need for a simplified, less time-consuming assessment tool that takes cross-cultural differences and specificities into consideration. PMID- 8010356 TI - Depression in Parkinson's disease. AB - OBJECTIVE: The authors assessed the prevalence of major depression (DSM-III-R) among Parkinson's disease patients and compared this rate with that of matched physically disabled subjects. METHOD: The 30-item General Health Questionnaire and measures of physical disability were completed by all patients in Dunedin, New Zealand, identified as having Parkinson's disease. Patients scoring over 5 on the General Health Questionnaire were interviewed with the Structured Clinical Interview for DSM-III-R--Non-Patient Version. Each patient living in the community was matched for age, sex, and level of physical disability with a comparison subject who did not have a neurological condition. RESULTS: Of the 73 subjects with Parkinson's disease who agreed to participate and were judged not to be demented, 34.2% scored higher than 5 on the 30-item General Health Questionnaire, but only 2.7% met the criteria for major depression. No difference from the comparison group was found. CONCLUSIONS: The prevalence of major depression in patients with Parkinson's disease may be no greater than in age- and sex-matched physically disabled persons. PMID- 8010357 TI - Validity of rapid cycling as a course specifier for bipolar disorder. AB - OBJECTIVE: This study's aim was to test the validity of rapid cycling, defined by criteria consistent with those proposed in the DSM-IV draft, as a course specifier for bipolar disorder. METHOD: The study was conducted at a university center for affective disorders on patients fulfilling Research Diagnostic Criteria for bipolar disorder. Thirty-seven rapid-cycling patients, i.e., patients with at least four affective episodes during the previous year, were compared with 74 nonrapid-cycling patients on several demographic and clinical variables. All patients were then followed up prospectively for 2-5 years by monthly personal interviews. RESULTS: The rapid-cycling group was significantly older and had a significantly longer illness duration than the nonrapid-cycling group but did not have a significantly higher percentage of women or frequency of current hypothyroidism. During each year of follow-up, the mean number of affective episodes and the percentage of patients with at least four affective episodes were significantly higher among rapid-cycling patients. Rapid-cycling patients with a pole-switching pattern during the year preceding intake were significantly more likely than other rapid-cycling patients to have at least four affective episodes during each of the first 4 years of follow-up. CONCLUSIONS: These findings support the practical usefulness of rapid cycling as a course modifier for bipolar disorder, since it identifies a patient subgroup with a high recurrence rate. The predictive value of the modifier may be enhanced by the requirement of a pole-switching pattern. Since no external (i.e., unrelated to course) validator was found, the idea that rapid cycling represents one extreme of a continuum of episode frequency in bipolar disorder remains viable. PMID- 8010358 TI - Suicide in bipolar disorder in Finland. AB - OBJECTIVE: The authors examined suicides of persons with bipolar disorder in aspects relevant to suicide prevention, including clinical features, treatment contacts, adequacy of treatment received, communication of suicidal intent, and suicide methods. METHODS: All suicide victims with DSM-III-R bipolar I disorder among all 1,397 suicides in Finland within a 12-month period were carefully studied using the psychological autopsy method and were compared to suicide victims with unipolar major depression. RESULTS: Thirty-one bipolar I victims were identified. Most suicides of persons with bipolar disorder occurred during a major depressive episode (79%), but in some cases it occurred during a mixed state (11%) or even during or immediately after remission of psychotic mania (11%). Men had a higher rate of comorbid alcoholism, a lesser mean age, and shorter treatment histories than women. Although 74% of the victims were receiving psychiatric care at the time of suicide, and 39% had even explicitly communicated their intent to health care personnel during the last 3 months, only 11% of those who were depressed had received adequate doses of antidepressants and none had received ECT. Only 32% of the bipolar patients were prescribed lithium. In comparison to unipolar depressed suicide victims, the bipolar victims had more divorces, longer treatment histories, and more frequent hospitalizations. CONCLUSIONS: Although late suicides were common among both male and female bipolar victims, suicide seemed to occur earlier among males. Most bipolar victims had had a recent psychiatric treatment contact, but few had received adequate treatment immediately before death. Suicide victims with unipolar and bipolar disorders differed in marital status and treatment history. PMID- 8010359 TI - Comparison of buprenorphine and methadone in the treatment of opioid dependence. AB - OBJECTIVE: This study compared the efficacy of buprenorphine and methadone in the treatment of opioid dependence. METHOD: Participants (N = 164) were relatively treatment-naive, opioid-dependent applicants to a 26-week treatment program who were randomly assigned to either methadone or buprenorphine treatment. Dosing was double-blind and double-dummy. Patients were stabilized on a regimen of either methadone, 50 mg, or buprenorphine, 8 mg, with dose changes possible through week 16 of treatment. Urine samples were collected three times a week, and weekly counseling was provided. RESULTS: Buprenorphine (mean dose = 8.9 mg/day) and methadone (mean dose = 54 mg/day) were equally effective in sustaining retention in treatment, compliance with medication, and counseling regimens. In both groups, 56% of patients remained in treatment through the 16-week flexible dosing period. Overall opioid-positive urine sample rates were 55% and 47% for buprenorphine and methadone groups, respectively; cocaine-positive urine sample rates were 70% and 58%. Evidence was obtained for the effectiveness of dose increases in suppressing opioid, but not cocaine, use among those who received dose increases. CONCLUSIONS: The results of this study provide further support for the utility of buprenorphine as a new medication in the treatment of opioid dependence and demonstrate efficacy equivalent to that of methadone when used during a clinically guided flexible dosing procedure. PMID- 8010360 TI - Methadone maintenance outcome as a function of detoxification phobia. AB - OBJECTIVE: Methadone maintenance outcome as a function of detoxification phobia was examined. METHOD: Opiate addicts (N = 271) in a 1983 random sample of methadone maintenance patients from three diverse populations were studied. Subjects from an individually assessed follow-up sample (N = 102) were compared on detoxification phobia. Logistic regression analysis yielded best predictors of the phobia. RESULTS: Phobic patients were more likely to be white, female, and abstinent; to have had fewer detoxification attempts and longer periods on maintenance; to show persistence of the phobia; to meet diagnostic criteria for depressive or anxiety disorders; and to have Addiction Severity Index scores above the 75th percentile for psychological problems. CONCLUSIONS: Detoxification phobia has a complex relationship to methadone maintenance outcome. It is associated with greater abstinence for patients in methadone maintenance treatment. However, for rehabilitated phobic patients it presents a barrier to successful detoxification and a drug-free adjustment that is often associated with other psychopathology but could be ameliorated by targeted assessment and treatment. PMID- 8010361 TI - Personality test scores as predictors of alcoholism almost a decade later. AB - OBJECTIVE: Comparisons of alcoholic and control subjects have revealed potential differences on a variety of personality tests. However, these results are difficult to interpret because subgroups of alcoholic subjects with antisocial personality disorder were often included in the overall analyses, and because testing was usually carried out while alcoholic subjects were in withdrawal. This article evaluates whether individuals' personality test scores at approximately age 20 predict their risk of subsequent development of alcohol abuse or dependence by about age 30. METHOD: As part of a larger prospective study of sons of alcoholic and control subjects, subsets of up to 78 subjects (39 matched pairs) out of a sample of 223 men took various personality tests that included the Eysenck Personality Inventory, subtests of the MMPI, and evaluations of locus of control and anxiety. An average of more than 9 years later, the incidence of alcohol abuse or dependence in these 223 subjects was determined by structured interviews. RESULTS: The 55 men who subsequently went on to develop alcohol abuse or dependence did not differ on any of the personality tests from the 168 men who did not develop alcoholism. CONCLUSIONS: These data are consistent with prospective studies indicating that except for antisocial personality disorder, it is difficult to identify a reliable personality profile associated with an individual's risk of alcoholism. PMID- 8010362 TI - Test-retest reliability of team consensus best-estimate diagnoses of axis I and II disorders in a family study. AB - OBJECTIVE: The present study examined the test-retest reliability of team consensus best-estimate diagnoses of axis I and II disorders. METHOD: As part of a series of family studies of outpatients with depressive and personality disorders, best-estimate diagnoses of relatives were derived in team diagnostic conferences held regularly over 4 years. Diagnoses were based on all available information, including direct interviews, family history data, and treatment records, and explicit guidelines were developed to resolve discrepancies between data sources. To evaluate the reliability of the team best-estimate diagnoses, 92 relatives were independently rediagnosed after a 2-year interval. RESULTS: The reliability of both axis I and II disorders was good to excellent. The results were similar for cases in which diagnoses were based on direct interviews plus informant data and cases in which diagnoses were based on informant data alone. CONCLUSIONS: These data indicate that the team consensus best-estimate diagnostic method can be applied consistently, even over an interval of several years. PMID- 8010363 TI - Reliability of diagnostic reporting for children aged 6-11 years: a test-retest study of the Diagnostic Interview Schedule for Children-Revised. AB - OBJECTIVE: This study examined the reliability of symptom reporting by community children of elementary school age and their parents on a version of the Diagnostic Interview Schedule for Children-Revised (DISC-R). METHOD: A sample of 109 children aged 6-11 years from an ongoing epidemiologic study were recruited for retest DISC-R interviews after completion of the study protocol. Retest interviews took place 7-18 days after the first interview and were conducted by interviewers who had no prior information about the subjects. Test-retest reliability for five common childhood psychiatric diagnoses was evaluated with the kappa statistic; the intraclass correlation coefficient was used to evaluate test-retest reliability of symptom scales. RESULTS: The reliability of the parents' reports on the DISC-R was good to excellent for attention deficit hyperactivity disorder and separation anxiety disorder; it was fair for overanxious disorder, oppositional defiant disorder, and conduct disorder. The children reported many fewer symptoms than the parents except for separation anxiety disorder; reliability was fair for separation anxiety disorder and poor for attention deficit hyperactivity disorder. The children were particularly unreliable in reporting about time factors, such as duration and onset of symptoms. When symptoms were considered without duration and onset, children's reports reached fair reliability for separation anxiety disorder, overanxious disorder, and attention deficit hyperactivity disorder but remained poor for oppositional defiant disorder. CONCLUSIONS: The results suggest that highly structured diagnostic interviews such as the DISC-R may not be appropriate for use with younger children of elementary school age in community-based studies. PMID- 8010364 TI - DSM-III personality disorders in the community. AB - OBJECTIVE: The aims of this study were to estimate the prevalence and investigate the comorbidity and potential consequences of DSM-III personality disorders in the community. METHOD: A total of 810 adults were examined in the second stage of the Eastern Baltimore Mental Health Survey in 1981, part of the National Institute of Mental Health Epidemiologic Catchment Area program. The subjects were directly examined by psychiatrists using a semi-structured method that allowed diagnosis of all DSM-III personality disorders as well as other DSM-III psychiatric disorders. RESULTS: The prevalence of personality disorders in these adults was 5.9% (9.3% when provisional cases were included). Men had higher rates than women, and subjects who were separated or divorced had the highest rates. There was little comorbidity among specific personality disorders. Subjects with personality disorders were significantly more likely to have a history of sexual dysfunctions, alcohol use disorders, and drug use disorders as well as suicidal thoughts and attempts. In addition, they reported significantly more life events in the past year. Among subjects with any axis I disorder, those with personality disorders were judged by the psychiatrists to be more in need of treatment; however, only 21% were receiving treatment. CONCLUSIONS: Personality disorders are relatively common in the community. They are associated with axis I disorders and life events. Only one-fifth of the individuals who qualify for diagnoses of personality disorders in the community are receiving treatment. PMID- 8010365 TI - Trazodone for antidepressant-associated insomnia. AB - OBJECTIVE: The authors investigated trazodone as a hypnotic for depressed patients who had persistent, exacerbated, or new insomnia while taking either fluoxetine or bupropion. METHOD: Seventeen depressed patients who had insomnia while taking fluoxetine or bupropion were given either trazodone or placebo in a double-blind crossover trial. Sleep was assessed by self-report with the Pittsburgh Sleep Quality Index and the sleep items of the Yale-New Haven Hospital Depressive Symptom Inventory. RESULTS: Improvement with trazodone, but not with placebo, was shown by the total Pittsburgh index scores and Yale-New Haven inventory total sleep scores and by the Pittsburgh index measures of sleep duration and Yale-New Haven inventory measures of early morning awakening, and there was a trend toward improvement in the Yale-New Haven inventory item regarding middle of the night awakenings. Subjective sleep quality and sleep latency also showed a trend toward improvement, but the Pittsburgh index measures of sleep efficiency and disturbances and the Yale-New Haven inventory item regarding difficulty falling asleep were unaffected by trazodone. One patient dropped out because of excessive daytime sedation with trazodone, and another dropped out because of nonresponse to placebo. Of the completers, 67% experienced overall improvement in sleep with trazodone according to a priori criteria, whereas only 13% experienced improvement with placebo. CONCLUSIONS: Trazodone is an effective hypnotic for patients with antidepressant-associated insomnia. PMID- 8010366 TI - Fewer dopamine transporter receptors in the prefrontal cortex of cocaine users. AB - The authors investigated dopamine transporter receptor binding in the post-mortem prefrontal cortex of 13 subjects with histories of cocaine use who had positive blood screens for cocaine at autopsy and 13 comparison subjects with no history of cocaine use and negative blood screens for cocaine at autopsy. Synaptosomes from pulverized prefrontal cortex were assayed with [3H]GBR 12935 for dopamine transporter receptor. There was a 38% decrease in number of binding sites but no change in affinity constants in the cocaine users. PMID- 8010367 TI - Comparison of measures used to determine substance abuse in an inpatient psychiatric population. AB - Eighty-nine of 178 consecutively admitted inpatients were administered the substance abuse sections of the Structured Clinical Interview for DSM-III-R- Patient Version (SCID-P). Patients also provided a urine sample for toxicologic analysis. In addition, primary clinicians assigned admission and discharge diagnoses. Test characteristics (e.g., sensitivity) for confirming a current diagnosis of psychoactive substance abuse were calculated for each measure and compared. Urine toxicology analyses and admission and discharge diagnoses were significantly less accurate in diagnosing psychoactive substance abuse than the SCID-P. This finding indicates that substance abuse is frequently not noted during routine admission and discharge assessments. PMID- 8010368 TI - Desipramine for the treatment of "pure" dysthymia versus "double" depression. AB - The authors report results of an 8-week, open trial of desipramine in 42 patients with DSM-III-R dysthymia with a concurrent diagnosis of major depression ("double" depression) and 33 patients with dysthymia who had no other depressive diagnosis ("pure" dysthymia). Either complete or partial remission was achieved by 70% of the patients with "pure" dysthymia. This compared favorably with but was not significantly different from results in the "double" depression group. PMID- 8010369 TI - Phototherapy for seasonal affective disorder: a blind comparison of three different schedules. AB - The authors investigated the outcome of an alternating time schedule versus two fixed schedules (either morning or evening) of bright light treatment for seasonal affective disorder. The subjects were 31 patients who met DSM-III-R criteria for major depression with a seasonal pattern. No statistically significant difference was observed among patients in the three groups for response criteria after 1 week of treatment. These results support the use of more flexible phototherapy schedules. PMID- 8010370 TI - Cisapride for the treatment of nausea produced by selective serotonin reuptake inhibitors. AB - A low dose of cisapride (5 mg b.i.d.) produced rapid relief from nausea elicited by the initiation of treatment with a selective serotonin reuptake inhibitor in eight patients. This effect of cisapride is presumably related to its serotonin3 antagonistic property. PMID- 8010371 TI - Suicide clustering in a psychiatric hospital with a history of a suicide epidemic: a quantitative study. AB - To determine if the suicides in a Finnish psychiatric hospital with a history of a suicide epidemic were clustered and if the sex distribution of the suicides followed a random pattern, the authors conducted statistical analyses of the temporal distribution and sex distribution of 59 consecutive inpatient suicides over the years 1967-1992 in the hospital. They found no statistically significant temporal clustering and that the sex distribution of the suicides was random. They conclude that inpatient suicide epidemics seem to be rare and separate events, related more to temporary micro-social factors and to the psychopathology of individual patients than to permanent characteristics of a particular hospital. PMID- 8010372 TI - Dose-dependent stuttering and dystonia in a patient taking clozapine. PMID- 8010373 TI - Treatment of clozapine-induced obsessive-compulsive symptoms with sertraline. PMID- 8010374 TI - Beneficial effects of buspirone therapy in Huntington's disease. PMID- 8010375 TI - Beliefs of hypochondriacal patients. PMID- 8010376 TI - Cholecystokinin octapeptide and bulimia nervosa. PMID- 8010377 TI - Transitional residences. PMID- 8010378 TI - Panic disorder and alexithymia: no overlap. PMID- 8010379 TI - Psychiatry's undiscovered country. PMID- 8010380 TI - Images in neuroscience. Human Brain receptors, VI. Ionotropic receptors. PMID- 8010381 TI - Does ECT alter brain structure? AB - OBJECTIVE: The purpose of this study was to evaluate whether ECT causes structural brain damage. METHOD: The literature review covered the following areas: cognitive side effects, structural brain imaging, autopsies of patients who had received ECT, post-mortem studies of epileptic subjects, animal studies of electroconvulsive shock (ECS) and epilepsy, and the neuropathological effects of the passage of electricity, heat generation, and blood-brain barrier disruption. RESULTS: ECT-induced cognitive deficits are transient, although spotty memory loss may persist for events immediately surrounding the ECT course. Prospective computerized tomography and magnetic resonance imaging studies show no evidence of ECT-induced structural changes. Some early human autopsy case reports from the unmodified ECT era reported cerebrovascular lesions that were due to agonal changes or undiagnosed disease. In animal ECS studies that used a stimulus intensity and frequency comparable to human ECT, no neuronal loss was seen when appropriate control animals, blind ratings, and perfusion fixation techniques were employed. Controlled studies using quantitative cell counts have failed to show neuronal loss even after prolonged courses of ECS. Several well controlled studies have demonstrated that neuronal loss occurs only after 1.5 to 2 hours of continuous seizure activity in primates, and adequate muscle paralysis and oxygenation further delay these changes. These conditions are not approached during ECT. Other findings indicate that the passage of electricity, thermal effects, and the transient disruption of the blood-brain barrier during ECS do not result in structural brain damage. CONCLUSIONS: There is no credible evidence that ECT causes structural brain damage. PMID- 8010382 TI - Depression, competence, and the right to refuse lifesaving medical treatment. AB - OBJECTIVE: The authors explore the possibility that psychiatrists inappropriately extend their views on suicide by the medically well to refusal of lifesaving treatment by the seriously medically ill. METHOD: The legal and bioethics literature on competence to refuse lifesaving treatment and the possible impact of depression on this refusal is reviewed. RESULTS: Over the past 20 years, the burden of proof concerning the mental competence of seriously medically ill patients who refuse lifesaving treatment has shifted to the persons who seek to override these refusals. However, in psychiatry a patient's desire to die is generally considered to be evidence of an impaired capacity to make decisions about lifesaving treatment. This contrast between ethical traditions is brought into clinical focus during the evaluation and treatment of medically ill patients with depression who refuse lifesaving treatment. The clinical evaluation of the effect of depression on a patient's capacity to make medical decisions is difficult for several reasons: 1) depression is easily seen as a "reasonable" response to serious medical illness, 2) depression produces more subtle distortions of decision making than delirium or psychosis (i.e., preserving the understanding of medical facts while impairing the appreciation of their personal importance), and 3) a diagnosis of major depression is neither necessary nor sufficient for determining that the patient's medical decision making is impaired. CONCLUSIONS: Depression can be diagnosed and treated in patients with serious medical illness. But after optimizing medical and psychiatric treatment and determining that the patient is competent to make medical decisions, it may be appropriate to honor the patient's desire to die. PMID- 8010383 TI - The prevalence and distribution of major depression in a national community sample: the National Comorbidity Survey. AB - OBJECTIVE: Major depression is a frequent and disabling psychiatric disorder in the United States. This report examines the prevalence and risk factor profile of both pure and comorbid major depression according to data from the National Comorbidity Survey. METHOD: To estimate the prevalence of psychiatric comorbidity in the United States, a national sample of 8,098 persons 15-54 years of age from the 48 conterminous states was surveyed with a modified version of the Composite International Diagnostic Interview. RESULTS: From the survey data the prevalence of current (30-day) major depression was estimated to be 4.9%, with a relatively higher prevalence in females, young adults, and persons with less than a college education. The prevalence estimate for lifetime major depression was 17.1%, with a similar demographic distribution. Both 30-day and lifetime prevalence estimates were higher than estimates from the earlier Epidemiologic Catchment Area study. When pure major depression was compared with major depression co-occurring with other psychiatric disorders, the risk factor profiles exhibited clear differences. CONCLUSIONS: These findings suggest a greater burden of major depression in community-dwelling persons than has been estimated from previous community samples. The risk factor profile showed significant differences between persons with pure and combined major depression. PMID- 8010384 TI - Impact of acute psychiatric inpatient treatment on major depression in late life and prediction of response. AB - OBJECTIVE: The authors conducted a prospective study to examine the sociodemographic and clinical characteristics of elderly inpatients with major depression and their response to acute psychiatric hospitalization. The relation between the descriptive variables and clinical response was also investigated. METHOD: The subjects were 205 consecutively admitted inpatients, whose mean age was 71 years, who met the DSM-III-R criteria for major depression. Each subject received detailed physical, psychiatric, and mental status examinations, along with quantitative assessments of psychiatric symptoms and cognitive performance at admission and at discharge. Management of physical problems was optimized, and patients were treated with a combination of somatic and psychotherapeutic interventions. The average duration of hospitalization was approximately 1 month. RESULTS: Despite considerable medical and psychiatric comorbidity, the patients responded well to treatment, as reflected by a 50% reduction in the average score on the Hamilton Depression Rating Scale. Nearly one-half of the patients had experienced the resolution of their depressive symptoms by the time of discharge. Race, cognitive performance at admission, number of medical problems, use of ECT, and length of hospitalization independently contributed to the prediction of clinical response. Response to treatment was not related to the other sociodemographic variables examined or to any of the indexes of severity of depressive episode. CONCLUSIONS: Short-term psychiatric hospitalization offers an effective and efficient vehicle for the treatment of severe or complicated cases of major depression in the elderly, even when considerable medical and psychiatric comorbidity is present. PMID- 8010386 TI - [Perinatal infant mortality and cesarean section]. AB - The authors looking for a connection between perinatal mortality (PM) and caesarean delivery (CD). A 15-year period has been analysed with 66,451 births, 943 PM cases and 3145 CD cases. The total PM and PM after CD show a tendency towards becoming equal towards the end of the investigated period. The authors consider that the margin of 10/1000 can not be influenced by the rate of the operation growing higher. PM after CD is mainly influenced by biological factors, doctor's qualifications, the timely stated reasons for the operation and the postoperative treatment and care for the baby. A conclusion has been drawn for the multiple factor caused of PM after CD. PMID- 8010385 TI - Psychotic unipolar depression at follow-up: factors related to psychosis in the affective disorders. AB - OBJECTIVE: The current research was designed to investigate the relationship between affective disruption and psychosis in unipolar major depressive disorder and to evaluate whether some depressed patients are particularly vulnerable to subsequent psychosis. METHOD: A group of 31 psychotic and 63 nonpsychotic inpatients with unipolar depression were assessed during hospitalization and then prospectively assessed for depressive and psychotic symptoms 2.4 years after hospital discharge. RESULTS: The psychotic depressed inpatients had significantly higher rates of psychosis during the posthospital period, 2.4 years later, than the originally nonpsychotic depressed inpatients. However, they did not have higher rates of depressive syndromes during the posthospital period. Psychosis during the posthospital period was significantly related to recurrent or persistent affective disruption. The posthospital depressive syndromes of the initially psychotic depressed inpatients tended to be slightly more severe than those of the initially nonpsychotic depressed inpatients. Despite this, psychosis during the inpatient period was more predictive of posthospital psychosis than the severity of the posthospital depressive syndrome. CONCLUSIONS: The interaction of the following two factors was proposed to be central to psychotic depression: 1) a vulnerability to psychosis, and 2) concurrent affective disruption. PMID- 8010388 TI - [The morphological characteristics of the cicatrix in repeat cesarean section]. AB - It has been established that the cicatrix formation after a Caesarean operation is conditioned by various factors remaining to a large extent an individual reaction. Cicatrix structure, its vascularization, its relationship with surrounding muscular tissue and the presence or absence of inflammatory changes have their peculiarities. By a number of biopsies from the cicatrix area after a Caesarean operation we have tried to estimate the sufficiency of the cicatrix studying its morphological characteristics. For the investigation 2-3 biopsies on the average were taken from a total of 58 women. The histological and histochemical methods applied enabled us to determine quite precisely the quality of the cicatrix. PMID- 8010387 TI - [Pre-eclampsia--the delivery and outcome for newborn infants]. AB - In the present research 50 patients have been examined having average and heavy form of preeclampsia who have entered and have been treated at the university hospital. The percentage of the Caesarean sections for the heavy forms is 72% while for the average forms it is 63%. The impression is that the heavier the preeclampsia is the more often operative delivery is practiced. On the other hand the heavier the preeclampsia is the quicker the delivery completes: approximately 50% of the heavy forms end with operative delivery up to the 32 gestational weeks while for the average forms the percentage is 6.6%. The birth information is compared to the values of Apgar score on the 1st and 5th minutes for the newborn and their outcome in the neonatal period. The general conclusion which is done concerns the optimal gestational time limit for birth in these cases in order to successful outcome for the newborn. PMID- 8010389 TI - [The dependence of fetal weight and fetal length at birth on the site of placental attachment]. AB - The present study shows the connection between the location of the placenta in utero and the neonatal weight and length after delivery and also the relative part of abdominal delivery in relation to placental location. 289 pregnant women have been examined with ultrasonography in the III trimester of pregnancy. The results show that the neonatal length and the weight are normal when the placenta is anterior, posterior or fundal. The least neonatal weight and length have been measured in cases of placenta praevia. No correlation was found between maternal age and placental location. PMID- 8010390 TI - [The motivation for deciding on keeping or terminating a pregnancy. II. The socioeconomic factors, the self-assessment of health status and the attitude towards the future]. AB - Subject of investigation are peculiarities of emotional and motivational sphere of women in a fertile age (women recently confined or terminating pregnancy by wish). They are divided according to their attitude towards real pregnancy. Results of investigation show that double-pole attitude towards pregnancy is in direct dependence on the employment, on the security of working place. Marriage and its duration are mutually connected with the negative attitude toward pregnancy. Pregnancy becomes unwished for when the number of children desired coincides with the real one. There is a considerable interconnection between pessimistic expectations and attitude toward pregnancy in the both groups (p < 0.05). As a whole 72 per cent of tested persons would like to have two children without special preferences regarding their sex. According to the data made out of the investigation desired number of children is connected with the satisfaction from living conditions, the woman's age and marriage duration, with the professional realization and faith in future. The authors consider that towards every pregnancy an individual approach is necessary with careful search and investigation of factors which define woman's attitude toward pregnancy. PMID- 8010391 TI - [Congenital bacterial infections in newborn infants--the incidence and diagnostic criteria]. AB - On the basis of the practical experience in the intensive care unit of the University Hospital of Obstetrics and Gynecology an attempt is made to establish the importance of a number of criteria for the diagnosis and prognosis of antenatal infection in newborn babies. In the survey included 578 newborn infants for the period I. 1990-IV 1991. The study determines the factors with the greatest diagnostic value and highest incidence with antepartal infections. The conclusion is made that an exact diagnosis requires the evaluation of a full screening for connatal infection and the presence of a whole complex of factors. PMID- 8010392 TI - [The colposcopic, cytological and histological changes in the cervix uteri of women under 20 with a first pregnancy]. AB - The study includes 42 pregnant women chosen at random under the age of 20, in their first trimester presented for voluntary termination of pregnancy. Colposcopic, cytologic and histological test was performed. Chronic, often acute, non-specific inflammatory changes were observed, probably connected with early sex life. The establishing of a histologically atypical results in 33.3% of the cases as well as the observation of 21.7% falsely negative results from the colposcopic study support the theory of pregnancy as a factor causing complication for diagnosis. The relatively low sensitivity of the cytology method and 16.7% false negative results none the less the existence of high specificity (100%) is due to coexistence of low-stage dysplasia (I and II stage) and chronic non-specific inflammatory processes and the early, pilot character of the research. PMID- 8010393 TI - [Serum E2 and progesterone levels in patients with atypical hyperplasia and endometrial carcinoma]. AB - The authors study the serum levels of E2 and progesterone in 62 women with endometrial cancer and in 16 with atypical hyperplasia. Twenty women in a premenopausal phase have been used as a control group. In the patients with AH and EC normo or hypoestradiolaemia have been found. A marked hypoprogesteronaemia has been observed, which is expressed mainly in patients with AH. The low concentrations of progesterone in patients in pre- and postmenopausal phase are important markers for increased morbidity. The study of the progesterone level should become a routine method in the group with high risk of development of endometrial cancer. PMID- 8010394 TI - [The early detection and screening of endometrial carcinoma by the progesterone test and uterine sonography]. AB - An attempt was made to examine the efficiency of the progesterone test and uterus sonography for ten-years period. The progesterone test was used for 621 patients, most of them from the University Obstetrics and Gynaecological Hospital in the town of Varna. Department of Obstetrics and Gynaecology as well as at the National Oncological Centre, Gynaecological Clinic--Sofia during the last few years. There have been found out deep knowledge in epidemiology, etiology and the present possibilities for early diagnostics of the endometrial cancer. All patients of a total number of 621 were in the postmenopausal period and received Progesterone as one-time medical administration. In 44 women bleeding occurred, and 31 of them agreed to undergo abrasio probatoria. 354 out of these 621 patients were examined by ultrasound B-picture after about 6 months to 1 year. 31 cases needed to be cleared-out additionally. The abrasio probatoria done later showed full correspondence to the ultrasound images with the exception of 6 cases. In 15 cases was found polyps endometrial, in 9 cases--atypical glandular hyperplasia, in one case--carcinoma in situ and in 6 cases--early endometrial cancer. PMID- 8010395 TI - [A trial of the inhibition of adrenal steroidogenesis in girls with hirsutism]. AB - It was tested the influence of 1 tablet Parlodel on the concentration of hypophyseal-ovarian and hypophyseal-adrenal hormones. It was established, that 1 tablet Parlodel reduces the level of testosterone and cortisol of all tested persons at the second hour of the investigation. The influence of 1 tablet Parlodel is stronger with young girls showing higher initial levels of prolactin and testosterone. PMID- 8010396 TI - [Pregnancy and labor disorders in women with the malformed corpus uteri syndrome]. PMID- 8010397 TI - [Neonatal birth trauma in relation to the means of delivery]. AB - The frequency of birth trauma has fallen considerably in recent years. This decline reflects in particular a greater tendency to perform a caesarean section when difficulties of delivery would appear. Birth trauma often causes not only early, but late and continuous illness in neonates. For this reason it is an important problem in neonatal practice. 1791 newborn have been investigated: 1515 (84.5%) by vaginal delivery, 177 (9.8%) by caesarean section, 38 (2.1%) by forceps, 18 (1.01%) by vacuum extraction and 43 (2.4%) by pelvic presentation. The results show the frequency of birth trauma (5.5%) and asphyxia (5.9%) by vaginal delivery and by operative methods (19.8%--S.C., 60.5%--F., 88.8%--V.E.) and their dependence on some factors: induction or stimulation of labor, meconium stained amniotic fluid, prolonged or extremely rapid labor. PMID- 8010398 TI - [Puerperal streptococcal sepsis]. AB - A series of 8 cases of puerperal sepsis caused by beta-haemolytic Streptococcus from group A is analysed, including two cases of death--of a mother and her newborn. Among the women in seven cases serotype 2 of beta-haemolytic Streptococcus from group A has been identified. The cases have been observed in the Delivery department as a result of the existing favorable conditions for the transmission of the infection. Most probably among these conditions are the negligence of the sterility of the obstetric service from the moment of admission in the ward as well as the possibility for personal contacts among the patients after delivery. The late diagnosis (after two cases of death--of a newborn and a mother) can be attributed to the atypical clinical course of the disease as well as to the negligence of the existing relatively simple methods for early diagnosis. Among the mothers in two of the cases after radical surgical treatment combined with antibiotics and in all the others--after the application of high doses of antibiotics alone, the septic conditions has been overcome. The authors stress on the existing possibilities for the development of streptococcal sepsis in the era of the effective treatment of infections caused by this agent with antibiotics and once more underline the role of the penicillins in cases of septic streptococcal infections. PMID- 8010399 TI - [The use of midazolam and flumazenil for short-term anesthesia in terminating an early pregnancy]. AB - Aim of the study is to assess the efficacy of flumazenil when used for recovery after midazolam-induced sedation in short acting, out-patient procedure like interruption of early pregnancy. A significantly faster recovery of the patients after injection of flumazenil was observed. When flumazenil was not used, patients remained drowsy, worse oriented, and less co-operative at 1.5 and 20 min after completion of abortion. There were no significant difference between the groups with and without flumazenil at the 60 min. In conclusion when it is possible to observe the patients for more than one hour, the application of flumazenil after sedation with midazolam is not necessary. PMID- 8010400 TI - [Laser therapy in oncological gynecology. A review of the literature]. PMID- 8010401 TI - [Difficulties in the diagnosis and treatment of uterine malformations]. AB - The authors shows detailed classification of Buttram and Gibbons for the Muller uterine anomalies. According this classification the anomalies are classified in 6 different groups based on the stage of insufficiency in the normal development. Many theoretical arguments have been made on the different malformations in groups. The stress has been put on the clinical view and the choice of a surgery behavior. Some special cases are described which caused difficulties with the diagnosis and the treatment. The anomalies in the different groups are illustrated in different figures. PMID- 8010402 TI - [A rare case of a retroperitoneally situated extrauterine pregnancy]. AB - The variety of the extrauterine pregnancy clinical picture makes even the most experienced clinicians affirm that "the most characteristic symptom of extrauterine pregnancy is the fact that in most cases it has no characteristic symptoms and each case has its specific features." In the author's opinion it is obviously a case of ectopic pregnancy in the ampullar part of the left tube on its way out like a tubal abortion. The still fresh chorionic villi have arroded the peritoneum of the posterior abdominal wall and reached the retroperitoneal surface carrying away the ampule. This localization is an extremely rare phenomenon. PMID- 8010404 TI - [A rare location of a ganglioneuroma in the area of the external genitalia]. PMID- 8010403 TI - [A rare combination of pregnancy and periodic disease treated with colchicine]. AB - The authors describe familial Mediterranean fever cases in the country for the first time. More uncommon is the combination of colchicin treatment during the pregnancy. The outcome for mother and child is favorable. Republic of Bulgaria is mentioned as a possible region of appearance of that illness. PMID- 8010405 TI - [The clinical study of the preparation ciprofloxacin in inflammatory gynecological diseases]. PMID- 8010406 TI - [Practical observations on the use of the Ortho-Gynest vaginal globules from the firm of Cillag--Switzerland]. PMID- 8010407 TI - [Artificial abortions in Bulgaria and their prevention]. AB - Authors go into one extremely important problem for the family, woman, natality and family planning in Bulgaria. Scarcely during the last years it can be observed a slight reduction of the frequency of induced abortions. The average age of women having an abortion is high--about 30, which shows, that induced abortion is still a method of regulation fertility in intergenetic interval. The rate of those who have induced abortion under the age of 19 in Bulgaria is 7.8 to 53.3%, in Czechoslovakia, 6.7%, in DDR--50.0%, Greece--68%, Hungary--8.9%, Sweden -15.8%. The rate of done again induced abortion is higher, that is a result of bad preventing activities during the first abortion. Similar is the tendency of growing number of unmarried women having an induced abortion, as it is in the other countries: from 16.4% in 1980 to 21.7% in 1987. Bulgaria is on the third place in Europe according to the absolute number of dead cases after abortion (maternity death, after Rumania and USSR). It can be mentioned that in Bulgaria women do not use the most modern and safest devices, medicines for interruption of pregnancy. PMID- 8010408 TI - [Doppler velocimetry of the fetal and the uterine-placental blood flows in pre eclampsia and fetal retardation]. AB - The aim of the authors is to point out the value of the Doppler velocimetry in the prediction of perinatal distress and the place of Doppler investigation in the management of high risk fetus. In 17 pre-eclamptic and 20 normotensive pregnant women, the blood flow velocity in the uterine and umbilical artery was investigated. It was proved that the changes in the blood flow velocity are feature of some placental disturbances that lead to fetal retardation. The place of that method is controversial for active obstetric management. PMID- 8010409 TI - [The zinc concentration of the maternal serum and the amniotic fluid in pregnancies with fetal neural defects in the second trimester]. AB - The object of the investigation are 120 pregnancies in the second trimester, 38 of which are with prenatally proved neural tube defects of the fetus (anencephaly, spina bifida, hydrocephaly) and 82 with morphologically normal developed fetuses. There have been examined vein blood of the pregnant woman and amniotic fluid after transabdominal amniocentesis as there has been determined zinc status in both of the biological fluids. The average serum's zinc concentration at malformed pregnancies is without statistically considerable difference in comparison with this of the group--healthy pregnancies. Amendable zinc's concentration at cases with neural tube defects are statistical considerably higher than these in the control group. A survey of literary data, devoted to the theory of zinc deficiency as a teratogen in the human pregnancy, has been made during the last years. Up to the author's opinion, there have been represented the most acceptable explanations about the abnormal values of the zinc amenable concentration at neural tube defects in the fetus. PMID- 8010410 TI - The mode of insertion of umbilical cord and vessels: association with maternal haemoglobin genotype, neonatal factors, and placental component volumes. AB - We investigated whether variations in mode of attachment of umbilical cords and vessels coincided with differences in maternal haemoglobin genotype and neonatal factors or placental micro-volumetric composition. The incidence of placentae with marginally inserted cords, or those in which umbilical vessels separated prior to insertion, was not statistically different in samples from sickle cell patients having haemoglobin-SS and haemoglobin-SC genotypes, as compared with haemoglobin-AA controls. Results obtained from analysis of variance (ANOVA) suggest that the mode of insertion (status) of umbilical vessels may have clinical significance, because it produced differences in the main effects associated with neonatal gestational age, placental weight, and placental index. Point counting stereology was employed to estimate the microscopic compartment volumes of placentae prior to an assessment of statistical association between the data obtained and the status of umbilical vessels and maternal haemoglobin genotype. Furcate placentae (with separated umbilical vessels) had statistically greater than normal volumes of villi, villous trophoblast, and syncytial knots. We deduce that furcate placentae are prone to early delivery, because they are heavier, having more voluminous villi with more trophoblast and syncytial knots than controls. PMID- 8010412 TI - Distribution of GABA-containing neurons in human frontal cortex: a quantitative immunocytochemical study. AB - Fresh biopsy specimens of human cerebral cortex were collected from patients suffering from deep-seated tumors requiring resection. GABAergic neurons were revealed in 50-microns-thick sections, for pre-embedding, and 1-micron-thick sections, for post-embedding GABA immunocytochemistry. In both thick and thin sections, the reaction product was found in neuronal cell bodies and in small profiles in the neuropil. In both preparations, GABA-containing somata were distributed evenly throughout the depth of the cortex. As best appreciated in the thicker sections, GABA-immunoreactive neurons belonged to a variety of morphological cell types with multipolar, bitufted or bipolar, and horizontal dendritic arbors. In the semi-thin sections sampled in the frontal cortex, the proportion of these neurons could be accurately evaluated and was found to be 21.2% +/- 4.8% of all cortical neurons. The average size of GABA-immunoreactive neurons was, in each layer, smaller than that of immunonegative neurons. The average soma size of both neuronal populations, immunoreactive and immunonegative for GABA, increased with depth. The comparison between the rat, cat, macaque monkey, and human GABAergic interneurons revealed similarities among primate brains, contrasting with the parameters (morphology, size, density) measured in rodents. These data are pertinent to the involvement of the GABAergic neurons in the shaping of receptive-field properties of cortical neurons in healthy brains and in pathologies involving the impairment of inhibitory neurotransmission. PMID- 8010411 TI - Development of the spinal nerves in the mouse with special reference to innervation of the axial musculature. AB - Development of the mouse spinal nerves was studied. On E11 (11th day of gestation), the primitive spinal nerve fascicle extended ventrally in the anterior half of the sclerotome. Spinal nerves in the forelimb region united with each other to form the primitive brachial plexus. Their terminal segment was covered by a peculiar cell mass. On E12, five primary branches developed along the primitive spinal nerve trunk. The ramus dorsalis was originally a cutaneous nerve, supplying two series of branches to the skin of the back. The medial series was derived from the dorsal ramus of C2-C8, and the lateral series from C8 and the more caudal dorsal rami. Nerves of the former series took the presegmental course through the intermyotomic space, while those of the latter the postsegmental course. The ramus cutaneous lateralis was a nerve that took the presegmental course to become cutaneous. The ramus intercostalis externus was a muscle branch whose distribution was restricted within the segment. The ramus anterior was a muscle branch from the end of the primitive spinal nerve trunk. The ramus visceralis connected a thoracic nerve with the para-aortic sympathetic cell cord. On E13-16 the ramus anterior secondarily gave off a cutaneous branch (ramus cutaneous anterior). The ramus intercostalis externus extended ventrally deep to the intercostalis externus muscle, crossing just caudal to the ramus cutaneous lateralis that secondarily gave off branches to the obliquus externus abdominis muscle. PMID- 8010413 TI - A scanning electron microscopic study of the normal development of the chick wing from stages 19 to 36. A supplement to the Hamburger and Hamilton staging system. AB - The purpose of a staging system is to stage embryos by morphology rather than chronology. This is particularly useful when embryos do not develop exactly synchronously, as in the case of the chick. At present the Hamburger and Hamilton (1951) series is universally used to stage chick embryos. The aim of the present study was to provide a series of morphological descriptions of the normal stages of development of the chick wing bud from stages 19 to 36, and to correct some errors of the original system which may be overlooked by those new to the chick wing bud as an experimental model, and who rely primarily on the Hamburger and Hamilton stage series. In addition, Summerbell's (1976) observations on the appearance of the cartilaginous elements made from alcian green-stained whole mounts have been correlated with the external appearance of the wing bud to provide a more complete understanding of the skeletal development that influences, and to some degree accounts for, the changes in external morphology. Scanning electron microscopy (SEM) has been used to obtain images of much greater resolution and detail than those available from Hamburger and Hamilton, whilst using comparable magnifications to those attainable using conventional dissecting microscopes. The number of somites across which the proximal part of the wing bud extends has been provided as a measure of the limb width at early stages (19-24). At certain stages there were clear differences between the characteristic wing bud features described by Hamburger and Hamilton and those observed in the present study.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8010415 TI - Lectin-binding patterns in the development of the cerebellum. AB - We studied the binding distribution of several lectins, Con A, DBA, UEA and WGA, in the embryonic development of the chick cerebellum between stages 18 to 45 of Hamburger and Hamilton. We observed a differential labeling (in intensity and distribution) in the migratory and cortical layers of the cerebellum anlage with these different lectins. The different distributions and modifications in the labeling pattern suggest intense variations of the glycoproteins and glycosaminoglycans in the extracellular matrix during development. These variations coincide with cellular and organizational phenomena in the migratory and cortical layers, and suggest compartmentalization of the Purkinje cell labeling. PMID- 8010414 TI - Pattern of trkB protein-like immunoreactivity in vivo and the in vitro effects of brain-derived neurotrophic factor (BDNF) on developing cochlear and vestibular neurons. AB - The cochleo-vestibular ganglion (CVG) contains the neurons connecting the sensory epithelia of the inner ear to the cochlear and vestibular nuclei in the medulla. Expression of trkB protein-like immunoreactivity was studied in the developing CVG, using both Western blot and immunocytochemistry on tissue sections. Specific immunoreactivity was observed in the CVG from the 12th gestation day (gd) to the first postnatal week, reflecting the presence of high-affinity receptors for brain-derived neurotrophic factor (BDNF), a member of the NGF family of neurotrophins. Whole explants and dissociated cell cultures of cochlear (CG) and vestibular ganglion (VG) from mouse embryos and postnatal specimens were grown in neurotrophin-free medium to assay changes in neurite outgrowth and neuronal survival in response to the addition of physiological concentrations (0-5 ng/ml) of BDNF. Exogenous BDNF (2 ng/ml) promoted neurite outgrowth and neuronal survival in explants of both CG and VG, and the effects were stage-dependent. The onset of the response to BDNF occurred at gd 11-12. The response then reached a maximum between 14 and 18 gd and subsequently decreased, although it remained significantly present during the first postnatal week. BDNF-induced response was no longer observed in the mature cochlear and vestibular ganglion (after 30 postnatal days). The effects of BDNF on neuronal differentiation and survival were dose-dependent, starting at 0.5 ng/ml, with saturation at 2 ng/ml and half maximal effect occurring between 1 and 1.5 ng/ml. On the basis of our results, we propose that BDNF may be physiologically involved in the control of both neuronal differentiation, and central and peripheral target-dependent neuronal death, in the CVG of embryos and early postnatal mice. BDNF may act alone or in cooperation with other neurotrophins to establish the afferent innervation of the inner ear sensory epithelium. PMID- 8010417 TI - Aspirin and bleeding after coronary artery bypass grafting. PMID- 8010418 TI - Histopathology after repeated intrathecal injections of preservative-free ketamine in the rabbit: a light and electron microscopic examination. AB - Epidural and spinal administration of ketamine has been used in humans. Single dose studies have shown that preservative-free ketamine lacks neurotoxic effects, but there are no studies after repeated administrations. The aim of this study was to examine the effects of daily administration of preservative-free ketamine. Fourteen New Zealand albino rabbits were assigned to two groups receiving either intrathecal preservative-free ketamine 5 mg, 0.5 mL 1% solution (eight rabbits) or saline 0.5 mL (six rabbits) once a day for 14 consecutive days. The rabbits had a total subcutaneous implanted intrathecal catheter, which was introduced during general anesthesia. On Day 15 the rabbits were anesthetized and in vivo fixated by transcardial perfusion with Tyrode's solution followed by a mixture of 2% glutaraldehyde and 1% formaldehyde in a 0.1 mol/L phosphate buffer. A segment 5 cm on each side of the catheter tip was removed and kept in a cold solution of the fixative. Light microscopic, electron microscopic, and morphometric examinations showed no differences between the spinal cords from the rabbits injected with ketamine versus saline. Intrathecal ketamine produced motor impairment for a period of 15 min. We conclude that repeated intrathecal administration of preservative-free ketamine confirms the lack of neurotoxicity from single-dose studies. PMID- 8010419 TI - Intrathecal cholinergic agonists lessen bupivacaine spinal-block-induced hypotension in rats. AB - Hypotension is an important side effect of spinal anesthesia. Intrathecal (IT) cholinergic agonists, including neostigmine (NEO), increase arterial blood pressure by stimulating spinal sympathetic neurons. Therefore, we tested the ability of IT cholinergic agonists to prevent the hypotensive effect of IT bupivacaine (BUP) (430 nmol) in rats instrumented with IT and arterial catheters. The mean arterial pressure (MAP) decreased 35 +/- 4 mm Hg (n = 10) after IT-BUP alone. In contrast, MAP did not significantly change after IT-BUP + IT-NEO (12.5 and 25 nmol; n = 5 for each dose). Intramuscular (IM) NEO was not effective, and MAP decreased 38 +/- 4 mm Hg after IT-BUP + IM-NEO (25 nmol; n = 5). Three additional cholinesterase inhibitors, physostigmine, edrophonium, and ambenonium, as well as the direct-acting cholinergic agonists carbachol, oxotremorine, and arecoline, each lessened the hypotension seen after IT-BUP. Furthermore, the nonselective muscarinic antagonist, atropine, as well as the M2 receptor selective antagonist, methoctramine, prevented the vasopressor effect of IT-NEO in our model. Finally, the nicotinic antagonist, mecamylamine, and the M1 selective antagonist, pirenzepine, did not affect the pressor effects of NEO in our model. In conclusion, IT cholinergic agonists lessen BUP spinal-block-induced hypotension in rats by a muscarinic dependent pathway. PMID- 8010416 TI - Mitral cell dendrites: a comparative approach. AB - Phylogenetically persistent structures such as the mitral cells of the vertebrate olfactory bulb undergo changes in their dendritic arbor in the course of evolution. The morphology of mitral cells and the main elements of the olfactory bulb circuit in all classes of vertebrates are reviewed in this paper. Most of the neuronal elements found in the mammalian olfactory bulb are present in anamniotes. However, in contrast to those of amniotes, the mitral cells of most anamniotes lack basal dendrites, and periglomerular cells are absent in fish. This suggests a different circuitry and therefore drastic changes in the processing of olfactory information within the olfactory bulb. Lateral inhibition, conferred by basal dendrites in anamniotes, must then utilize other mechanisms in anamniotes. Moreover, the marked segregation of olfactory inputs onto mammalian mitral cells is less obvious in mitral cells of anamniotes that lack basal dendrites. The general role of dendrites, including those of mitral cells, is discussed in the light of increasing evidence for dendritic excitability. The evolutionary significance of mitral cell basal dendrites is also discussed. PMID- 8010420 TI - Anesthetic and hemodynamic effects of single bolus versus incremental titration of hyperbaric spinal lidocaine through microcatheter. AB - This study examined anesthetic development and hemodynamic changes during two techniques of hyperbaric lidocaine administration through 27-gauge intrathecal catheters for continuous spinal anesthesia in 55 elderly patients undergoing transurethral prostatic resection. Twenty-five patients were randomly assigned to receive hyperbaric lidocaine 5% solution in a single bolus of 75 mg to achieve blockade to approximately T6, and 30 patients to receive hyperbaric lidocaine 2.5% solution in increments of 25 mg to achieve T6 or to a maximum of three doses. Hemodynamic measurements of arterial pressure, heart rate, cardiac output, stroke volume, and ejection fraction were made serially after the induction of spinal anesthesia. Anesthesia failed to spread beyond the sacral region in 9/25 (36%) patients in the single-dose group (SD), but was successfully induced in all patients given titrated doses (TD) at total doses of 50 mg (n = 15) (TD50) and 75 mg (n = 15) (TD75). The mean maximal level of sensory block in all three groups was comparable: T5, T4, and T6 in groups SD, TD50, and TD75, respectively. The onset and progression of sensory block were rapid and similar in the SD and TD50 groups, in contrast to a gradual, stepwise development of block in group TD75. Grade 3 motor block occurred in response to the first dose of 25 mg lidocaine in 7/30 (23%) patients receiving titrated doses, but the overall incidence of leg paralysis did not differ among the three groups by the end of lidocaine dosing. Mean arterial pressure (MAP) decreased significantly relative to baseline in all three groups.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8010421 TI - The use of Quincke and Whitacre 27-gauge needles in orthopedic patients: incidence of failed spinal anesthesia and postdural puncture headache. AB - This study examined the incidence of failed spinal anesthesia and postdural puncture headache using a 27-gauge Whitacre and a 27-gauge Quincke needle in patients undergoing elective inpatient orthopedic procedures. The overall rate of failed spinal anesthesia was 8.5% [95% confidence interval (CI) = 4.6%-12.4%] (n = 17) in the Quincke group (n = 199) and 5.5% [95% CI = 2.3%-8.7%] (n = 11) in the Whitacre group (n = 199). This difference was not statistically significant. The overall incidence of postdural puncture headache (PDPH) was 0.8%; 1.1% [95% CI = 0%-2.4%] (n = 2) in the Quincke group and 0.5% [95% CI = 0%-1.5%] (n = 1) in the Whitacre group. These differences were not statistically significant. All headaches were classified as mild and resolved spontaneously with conservative management. The mean time for withdrawal of the stylet to appearance of cerebrospinal fluid was 10.8 +/- 6.9 s in the Quincke (n = 31) and 10.7 +/- 6.8 s in the Whitacre group (n = 33). These differences were not statistically significant. Our results suggest that both needles are associated with a very low incidence of PDPH and an incidence of failed anesthesia of 5.5%-8.5%. PMID- 8010422 TI - Optimal regional anesthesia for circumcision. AB - Dorsal penile nerve block (DPNB) is a useful procedure for analgesia in circumcision. It has minor complications and a reported failure rate of from 4% to 6.7%. To evaluate the intraoperative value of additional anesthesia of the perineal nerves--a branch of the pudendal nerve--during circumcision, we conducted a prospective randomized double-blind study on 250 adults. The postoperative period was not studied. The subpubic space technique of DPNB was used. Patients received DPNB (Group I) or DPNB with an additional ventral injection (Group II) for perineal nerve analgesia. Seventeen patients (13.6%) from Group I suffered pain. Of these, nine (7.2%) had discomfort and mild pain but no supplemental analgesia was needed. In the remaining eight patients, however, it was necessary to add local analgesia. This represents a total failure rate of 6.4%. On the other hand, only six patients (4%) in Group II had a mild diffused discomfort with no need for additional local anesthesia (P < 0.01). The average operating time was 12.4 +/- 2.7 min (range 9-22 min) in Group I and 10.7 +/- 1.6 min (range 8-15 min) in Group II (P < 0.001). We think that perineal nerves play an important part in innervation of the penis and must be anesthetized during the penile block. PMID- 8010423 TI - Nasal intubation with Bullard laryngoscope: a useful approach for difficult airways. AB - Since the original technique using the Bullard laryngoscope requires considerable practice to be reliable, we have developed an easier method with a directional tip endotracheal tube through the nostril. We first examined the feasibility of our method in patients with or without difficult airways. All 26 patients with difficult airways were successfully tracheally intubated with our method, and times for visualization and intubation were not different from those in 10 patients with normal airways. We further examined the direction of the tips of endotracheal tubes through the nostril in 128 patients with normal airways using four combinations of two kinds of both laryngoscopes (Bullard and Macintosh) and endotracheal tubes (directional-tip tube: Endotrol, Mallinckrodt Laboratories, Athlone, Ireland; or straight distal-end tube: Blue Line, Portex Ltd., Hythe Kent, United Kingdom). We found that a combination of the Bullard laryngoscope and the Endotrol tube had a higher probability of accessing the center of the glottis than the others. In conclusion, nasal insertion of a directional-tip tube assisted by the Bullard laryngoscope is an assured and prompt procedure for intubating the tracheas of patients with difficult airways. PMID- 8010424 TI - Assessment of an interactive learning system with "sensorized" manikin head for airway management instruction. AB - An interactive, self-study learning system for airway management instruction that utilizes a "sensorized" manikin head (Actronics Inc., Pittsburgh, PA) was compared to didactic instruction from anesthesiologists during third-year medical student anesthesia rotations. Before students were allowed to participate in airway management on anesthetized patients, they were randomly separated into two groups. One group received instruction from the learning system, and the other group was given a lecture with guided practice on a standard tracheal intubating manikin. Differences between groups were then assessed using 22 separate variables as all students performed actual airway management on patients undergoing general anesthesia. Anesthesia faculty, residents, and nurse anesthetists, blinded to group, served as assessors. There were 48 and 49 students in the didactic instruction and learning system groups, respectively. Beginning experience level of students with respect to airway management was similar between groups before the anesthesia rotations. There were 185 and 188 evaluation forms completed to assess the didactic instruction and learning system groups, respectively. Demographic data regarding patients were recorded. Patients in the learning system group on whom students performed airway management were older, had a larger average body mass index, and their airways more frequently received higher Mallampati classifications (glottic structures more difficult to visualize). No difference in the quality of airway management efforts or in students' appraisal of their own performances was seen between groups. Neither group demonstrated more rapid development of psychomotor skills. Students were equally satisfied with both methods of instruction.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8010425 TI - Phenylephrine does not reduce cerebral perfusion during canine cardiopulmonary bypass. AB - Gaseous microemboli during cardiopulmonary bypass (CPB) could injure the blood brain barrier so that cerebral vasoconstriction would result from infusing alpha agonist drugs, such as phenylephrine. Cerebral blood flow (radioactive microspheres) and metabolism were measured in seven dogs after rewarming from 150 min hypothermic CPB with bubble oxygenators used to produce gaseous microemboli. Phenylephrine (40 micrograms/min) was infused directly into the brachiocephalic artery so that aortic pressure before (80 +/- 2 mm Hg) and during (79 +/- 3 mm Hg) the infusion did not change. Neither blood flow to the cerebral hemispheres (P = 0.960), cerebellum (P = 0.854), and brainstem (P = 0.694) nor the cerebral metabolic rate for oxygen (P = 0.862) differed when values obtained before and after 30 min of phenylephrine infusion were compared. Cerebral vascular resistance was also unchanged by phenylephrine, being 1.22 +/- 0.10 mm Hg.mL 1.min-1 x 100 g-1 before infusion and 1.25 +/- 0.17 mm Hg.mL-1.min-1 x 100 g-1 during infusion (P = 0.849). Phenylephrine does not cause cerebral vasoconstriction after rewarming from hypothermic CPB, a finding which suggests that the blood-brain barrier is preserved during bypass. PMID- 8010426 TI - Response to succinylcholine in porcine malignant hyperthermia. AB - The purpose of this study was to gain new insights in the role of succinylcholine in the initiation of malignant hyperthermia (MH). The intravenous (i.v.) administration of succinylcholine (2.0 mg/kg) induced fasciculations and masseter spasm in both normal swine and those susceptible to MH. However, the amplitudes and durations of generalized fasciculations were significantly greater in the susceptible animals that subsequently developed a fulminant episode of MH: succinylcholine induced not only tachycardia, hyperthermia, contractures, and increases in PaCO2 and lactate, all classic indicators of an episode, but also an initial severe hypotension. The mean arterial pressure in these swine decreased from 115 +/- 6 mm Hg to 60 +/- 12 mm Hg (mean +/- SD), 1 min after the administration of succinylcholine. Normal swine developed neither cardiovascular effects nor altered metabolism in response to succinylcholine. The pretreatment of animals with a nondepolarizing muscle relaxant (pancuronium 0.1 mg/kg) minimized fasciculations induced by succinylcholine, but did not prevent the hypotension nor episodes of MH in the susceptible swine. In the pretreated and untreated susceptible swine, dantrolene was an equally effective treatment. Plasma catecholamine levels after succinylcholine administration were increased only in the susceptible swine without the pancuronium pretreatment. We concluded that the effects of succinylcholine on skeletal muscle and/or on other tissues play a significant role in the initiation of a MH episode in swine with this genetic disorder, and that these effects are not dependent on an abnormal sensitivity for succinylcholine-induced skeletal muscle fasciculations in these animals. PMID- 8010427 TI - Residual pneumoperitoneum: a cause of postoperative pain after laparoscopic cholecystectomy. AB - After laparoscopic cholecystectomy, residual gas is inevitably retained in the peritoneal cavity. An active attempt is not always made to remove it. Using a double-blind prospective protocol in 40 healthy patients, we evaluated the effect of residual pneumoperitoneum on post-laparoscopic cholecystectomy pain intensity. On completion of surgery, prior to removal of the surgical instruments, the patients were randomly divided into two groups: in the active aspiration (AA) group an active attempt was made to remove as much gas as possible from the peritoneal cavity, while in the nonactive aspiration (NAA) group no such effort was made. Postoperative pain was assessed hourly over a 4-h period with a visual analog scale (VAS) and a patient-controlled analgesia (PCA) device. During the first postoperative hour, the NAA patients made significantly (P < 0.05) more demands (mean +/- SD) for morphine than those in the AA group (31.3 +/- 26.2 vs 15.3 +/- 15.7) and also received a borderline significantly (P = 0.056) larger dose (mean +/- SD) of PCA morphine (3.9 +/- 1.9 mg vs 2.7 +/- 1.3 mg). The VAS scores (mean +/- SD) over the 4-h study period were similar in both groups, being high during the first postoperative hour (AA = 5.1 +/- 2.1 vs NAA = 6.1 +/- 2.2) and then decreasing. We conclude that residual pneumoperitoneum is a contributing factor in the etiology of postoperative pain after laparoscopic cholecystectomy. PMID- 8010428 TI - A method for estimating the delivery temperature of intravenous fluids. AB - Despite rigorous efforts to monitor and control the fluid temperature within a warmer, the actual delivery temperatures of intravenous (i.v.) fluids at a patient infusion site are not assessed in current clinical practice. A method which correlates the warmer temperature with the delivery temperature will provide the appropriate quality assurance framework. For fluids administered through typical 0.260- and 0.300-cm-diameter polyvinyl chloride (PVC) i.v. tubing, we developed such a method by directly measuring the delivery temperatures for saline, 6% hydroxyethyl starch (HES), 5% albumin, plasma, and packed red cells (PRC) using intratubing thermocouple wire probes. A kinetic analysis of the data yielded the following relationship governing temperature equilibration for fluids in i.v. tubing: f = L/(24 Q + L), where f represents the equilibration fraction, L the tubing length (cm), and Q the flow rate (mL/min). The equilibration fraction f is defined as (Ti - Td)/(Ti - Ta), where Ti, Td, and Ta represent the initial fluid temperature, the delivery temperature, and the ambient air temperature in centigrade, respectively. Both the fluid type and the variability in tubing construction had negligible effects on the delivery temperature. Under given conditions of Q and L, the relationship enables the calculation of the temperature equilibration fraction f and, subsequently, the delivery temperature. Furthermore, the i.v. tubing length or the particular L/Q may be calculated for a desired target temperature and the corresponding f. We conclude that, despite many complicating variables, one can effectively assess and even control the delivery temperature of i.v. fluids administered through typical i.v. tubing.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8010429 TI - The effect of heated wire circuits on humidification of inspired gases. AB - We performed this study to determine the effect of heated wire circuits on humidity delivered by several humidifiers commonly used during anesthesia. Humidifier bases from three manufacturers with several humidifying chambers for each base were tested using both heated and unheated circuits. Delivered humidity and circuit temperature were measured at the distal end of the circuit. Each chamber was tested under both continuous flow (CF) and intermittent flow (IF) conditions. IF was provided by a Servo 900 B ventilator. Adjustments of flow and volume were made for pediatric chambers. At 90 L/m CF, humidifier performance was unsatisfactory with both heated and unheated circuits. At 15 and 45 L/m CF, both distal circuit temperature (DCT) and humidity were within acceptable limits; unheated circuits delivered more humidity than heated circuits (P < 0.05). Relative humidity was lower at 45 L/m CF than at 15 L/m (P < 0.05). During IF while all chambers provided satisfactory humidity, humidity was greater when unheated circuits were used. We conclude that when heated circuits are used, humidifying systems may fail to deliver 100% humidity to patients. PMID- 8010431 TI - Complete recovery after prolonged resuscitation and cardiopulmonary bypass for hyperkalemic cardiac arrest. PMID- 8010430 TI - Cardiac sympathovagal balance and peripheral sympathetic vasoconstriction: epidural versus general anesthesia. AB - Both epidural and general anesthetics alter autonomic balance. However, the relative differences between epidural (EA) and general anesthetics (GA) with regard to cardiac and peripheral sympathovagal balance have not been described. Twenty consecutive patients scheduled for radical retropubic prostatectomy were randomized to receive EA (n = 10) or GA (n = 10). Power spectral analysis was performed on the electrocardiographic recordings, with the ratio of low (0.05 0.125 Hz)/high (0.125-0.5 Hz) frequency power used an index of cardiac sympathovagal balance. The forearm minus fingertip skin-surface temperature gradient (> 4 degrees C) was used as an indicator of sympathetically mediated peripheral vasoconstriction. Patients in the EA group demonstrated a significantly greater low/high frequency power ratio and a more frequent incidence of peripheral vasoconstriction than the GA group during the intraoperative period. During the postoperative period, the GA group demonstrated an increase in the low/high ratio and the incidence of vasoconstriction relative to the intraoperative period. Intraoperatively, upper body vasoconstriction appears to be accompanied by a significant shift in cardiac sympathovagal balance toward sympathetic predominance with EA relative to GA. Postoperatively, GA is associated with a shift in the sympathovagal balance toward sympathetic predominance. Further research is required to determine whether this results in cardiovascular compromise in the high-risk patient. PMID- 8010432 TI - A case of "stunned myocardium" after noncardiac surgery: increased concentration of plasma brain natriuretic peptide. PMID- 8010433 TI - Effects of the serotonin-receptor agonist sumatriptan on postdural puncture headache: report of six cases. PMID- 8010434 TI - Epidural anesthesia for a patient with moyamoya disease presenting for cesarean section. PMID- 8010435 TI - Obstruction of a double-lumen endotracheal tube by a saber-sheath trachea. PMID- 8010436 TI - The serotonin syndrome in a patient receiving sertraline after an ankle block. PMID- 8010437 TI - The deltoid sign. PMID- 8010438 TI - False alarms and the integrated alarm system: report of a potential hazard. PMID- 8010439 TI - Reinforced endotracheal tube obstruction. PMID- 8010440 TI - Reinforced orotracheal tube obstruction: pharyngeal or oral? PMID- 8010441 TI - More on the epidural test dose. PMID- 8010442 TI - When hypotension during laparoscopic cholecystectomy indicates termination of the laparoscopy. PMID- 8010443 TI - Push and pull: move your anesthesia machine more easily. PMID- 8010444 TI - The APL valve as a pressure-cycle ventilator during cardiopulmonary bypass for correction of congenital heart disease. PMID- 8010445 TI - Is blood warming before transfusion a safe procedure? PMID- 8010446 TI - A pediatric end-tidal carbon dioxide sampling port. PMID- 8010447 TI - Autoclaving laryngeal masks. PMID- 8010448 TI - On the "curare cleft". PMID- 8010449 TI - Cardiac electrophysiologic effects of diltiazem in dogs receiving either enflurane or chloralose anesthesia. AB - Previously we have described impaired myocardial conduction in patients receiving diltiazem and enflurane. The present study examines the possible mechanism(s) which may account for our clinical observation and presents methods of reversing adverse interactions. Nineteen mongrel dogs were randomized into two exposure groups: enflurane or chloralose anesthesia. Stepwise increasing doses of diltiazem were administered until predetermined endpoints were reached. Sinus and atrioventricular (AV) node function was assessed at all levels of diltiazem infusions, and after reversal drugs. Depression of AV nodal conduction and refractoriness after diltiazem administration was greater during enflurane anesthesia when compared with chloralose. There was severe sinus node dysfunction in enflurane-anesthetized animals. These effects were only reversed by isoproterenol. Patients may be at increased risk for severe sinus node depression when diltiazem is administered during enflurane anesthesia. This is due to a potent interaction between diltiazem and enflurane on the sinoatrial node. PMID- 8010450 TI - Comparison of pH-adjusted bupivacaine 0.75% and a mixture of bupivacaine 0.75% and lidocaine 2%, both with hyaluronidase, in day-case cataract surgery under regional anesthesia. AB - Alkalinized bupivacaine 0.75% (pH 6.8) and a mixture (1:1) of bupivacaine 0.75% and lidocaine 2%, both with hyaluronidase, were compared in regional ophthalmic anesthesia for day-case cataract surgery. Eighty-two patients were randomized into two groups (n = 39 and 43) to receive one of the two solutions in a double blind manner. Two intraorbital injections were administered initially: an inferolateral intraconal injection (3 mL) and a medial extraconal injection (3.5 mL). The progress of lid and globe akinesia was examined every 2.5 min up to 25 min and postoperatively. The block was supplemented at 10 and 20 min, if needed. Significantly better globe akinesia was achieved with the bupivacaine-lidocaine mixture; the patients who had received alkalinized bupivacaine needed additional injections significantly more often at 10 and 20 min. In lid akinesia, the onset time and recovery were similar in the two groups. One patient in the alkalinized bupivacaine group felt intraoperative pain, and eight patients in the bupivacaine lidocaine group and seven in the alkalinized bupivacaine group sensed pain postoperatively from corticosteroid and antibiotic injections. Seventy percent of the pH-adjusted bupivacaine group and 8% of the lidocaine-bupivacaine group had diplopia the day after surgery. Of the two local anesthetic mixtures studied, lidocaine (2%) with bupivacaine (0.75%) provided regional ophthalmic anesthesia of better quality. PMID- 8010451 TI - Aspirin does not increase homologous blood requirements in elective coronary bypass surgery. AB - Studies have demonstrated increased homologous blood product requirements in patients on aspirin (ASA) undergoing cardiac surgery. We reexamined the influence of ASA therapy on hemorrhage and transfusion requirements in patients undergoing elective coronary artery bypass (CAB) surgery in light of recent transfusion sparing practices and autologous cell salvaging techniques. Records from 197 patients who underwent reinfusion of postoperatively shed mediastinal autologous whole blood were retrospectively reviewed, including 87 patients who received ASA within 1 wk prior to surgery and 110 control patients. Patients undergoing repeat cardiac operations were excluded from the study. Cardiopulmonary bypass (CPB) duration, procedure length, aortic cross-clamp time, and number of grafts performed did not differ significantly between groups. None of the patients required reexploration for bleeding. There was significantly more mediastinal tube drainage in the ASA group (27%), but it did not affect homologous blood component requirements because this blood was autotransfused. In addition, there were no significant differences in platelet, fresh frozen plasma, and cryoprecipitate use between the groups. Thus, ASA did increase bleeding but did not increase homologous blood transfusion requirements in elective CAB surgery. PMID- 8010453 TI - Adenosine produces pulmonary vasodilation in the perfused rabbit lung via an adenosine A2 receptor. AB - Adenosine is a potent pulmonary vasodilator that has been used in therapy for clinical and experimental pulmonary hypertension. To determine the receptor responsible for adenosine-induced pulmonary vasodilation, we studied the relative potency of four adenosine agonists in the isolated buffer-perfused rabbit lung during pulmonary hypertension due to infusion of the thromboxane A2 mimetic U46619. The ED50 values for pulmonary vasodilation were 1.9 x 10(-8) mol/L for 5' N-ethylcarboxamidoadenosine (NECA), 4.5 x 10(-8) mol/L for 2-phenylaminoadenosine (CV-1808), 2.6 x 10(-6) mol/L for R(-)-N6-(2-phenylisopropyl) adenosine (R-PIA), and 6.5 x 10(-6) mol/L for cyclopentyladenosine, results consistent with an adenosine A2 receptor. Pretreatment with the adenosine A1 receptor antagonist cyclopentyltheophylline did not affect the dose-response curve to NECA, and pretreatment with the adenosine A2 receptor antagonist CGS 15943A increased the ED50 of NECA to 2.7 x 10(-7) mol/L. These results suggest that adenosine produces pulmonary vasodilation via activation of an adenosine A2 receptor. PMID- 8010452 TI - Serum but not plasma produces injury in the perfused rabbit lung. AB - Serum contains proteins that may produce lung injury directly by affecting endothelial cells and indirectly by modulating the effects of endotoxin (lipopolysaccharide). We studied the effects of 10% serum, 10% plasma, and 10% plasma plus 2 micrograms/mL lipopolysaccharide on pulmonary hypertension and vascular permeability in the isolated perfused rabbit lung. Control lungs perfused with Krebs-Henseleit buffer containing 3% albumin for 2 h had stable pulmonary vascular pressures and permeability (measured by the capillary filtration coefficient). Serum produced pulmonary hypertension and increased pulmonary vascular permeability. In contrast, plasma, with and without lipopolysaccharide, did not alter pulmonary vascular pressures or permeability. Pretreatment with the cyclooxygenase inhibitor indomethacin prior to the addition of serum prevented the serum-induced increase in pulmonary vascular pressures and permeability. We conclude that the deleterious effects of serum are not due to plasma proteins per se, but instead are related to activation of the coagulation cascade during preparation of the serum. The deleterious effects of serum appear to be mediated by cyclooxygenase metabolites of arachidonic acid. Finally, endotoxin, even with the addition of plasma, does not directly produce lung injury. PMID- 8010454 TI - Effects of sevoflurane on central nervous system electrical activity in cats. AB - We analyzed the effect of a new volatile anesthetic, sevoflurane (2%-5% in oxygen) on the electroencephalogram (EEG) of the neocortex, amygdala, and hippocampus, cortical somatosensory evoked potential (SEP), and brainstem reticular multiunit activity (R-MUA) in cats. Sevoflurane suppressed the background activity of the neocortex more than the amygdala and hippocampus. With increasing concentration of sevoflurane, the cortical EEG progressed from high amplitude slow waves to a suppression-burst pattern, which was followed by an isoelectric pattern and then spikes with isoelectricity. The amplitude of the SEP was augmented and the R-MUA was suppressed by sevoflurane in a dose-related manner. Repetitive peripheral electrical stimulation induced generalized seizures at 5% sevoflurane in 2 of 13 cats. These results suggest that sevoflurane suppresses the background central nervous system electrical activities in a dose related manner, leaving the reactive capabilities facilitated at deep anesthesia. PMID- 8010456 TI - The effect of anesthetics on neurologic outcome during the recovery period of spinal cord injury in rats. AB - We evaluated the effects of anesthetics on neurologic outcome in a model of recoverable experimental spinal cord injury (SCI). Adult rats were implanted with various sizes of hygroscopic plastic material at the T12 spinal level to determine the dimensions that would produce a progressive neurologic deficit from which recovery could occur. Neurologic evaluation was conducted on an inclined plane, noting the maximum angle at which an animal was able to maintain orientation perpendicular to the longitudinal midline. Scores were statistically modeled for each group to develop profiles of neurologic deficits. Rats were subjected to a 4-h exposure to isoflurane, fentanyl/nitrous oxide, or ketamine 7 or 8 days postimplantation. Neurologic outcomes were compared to a SCI reference group which received no postimplant anesthesia. An animal weight/desiccated implant volume (Wa/Vi) ratio of 53 to 73 g/mm3 produced postimplant neurologic deficits which deteriorated to near maximum within 3 days, followed by a gradual improvement beginning at Day 8 and returning to near normal between 21 and 25 days. Final outcome was based on modeled ramp scores for each group and reported in degrees +/- SD: reference, 71.2 +/- 1.1; fentanyl/N2O, 70.4 +/- 0.3; isoflurane, 72.6 +/- 1.1; and ketamine, 64.9 +/- 0.6. The fentanyl group attained maximum recovery first (P > 0.05) but did not recover to a level different on the average from the reference group. The ketamine group demonstrated a poorer (P > 0.05) recovery level relative to the other anesthetic protocols. PMID- 8010455 TI - The effects of halothane and isoflurane on cerebrocortical microcirculation and autoregulation as assessed by laser-Doppler flowmetry. AB - The effects of volatile anesthetics on red blood cell flow in the cerebral microcirculation have not been compared. We used laser-Doppler flowmetry, which measures red blood cell flow in the microcirculation to compare the effects of differing concentrations of isoflurane and halothane on cerebrocortical microcirculation. Sprague-Dawley rats were anesthetized with pentobarbital (65 mg/kg intraperitoneally). The animals were tracheotomized, paralyzed, and artificially ventilated. In the first protocol laser-Doppler flow (LDF) was recorded at 0.5, 1, 1.5, and 2 minimum alveolar anesthetic concentration (MAC) halothane or isoflurane, with blood pressure controlled by intravenous phenylephrine infusion (0.5-5 micrograms.kg-1.min-1). In the second protocol the effects of 0.5 and 1.5 MAC halothane and isoflurane on LDF changes in response to changes in mean arterial blood pressure (MABP) were compared. MABP was increased by phenylephrine infusion and decreased by hemorrhage. LDF increased with each 0.5 MAC increase in halothane and isoflurane concentration (P < 0.05). LDF was greater at 1.5 and 2 MAC isoflurane than at equi-MAC halothane (P < 0.01). Autoregulation of LDF was present but attenuated at MABP of 60-140 mm Hg at low halothane and isoflurane concentrations. LDF was increased at 1.5 MAC vs 0.5 MAC for both drugs (P < 0.01). The autoregulation coefficients (percent LDF change/mm Hg MABP change) were 0.41 +/- 0.10, 0.42 +/- 0.07, 0.27 +/- 0.04, and 0.20 +/- 0.05 at 0.5 MAC halothane, 0.5 MAC isoflurane, 1.5 MAC halothane, and 1.5 MAC isoflurane, respectively.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8010457 TI - Anesthesia for electroconvulsive therapy: effects of propofol and methohexital on seizure activity and recovery. AB - The influence of methohexital and propofol on seizure activity and recovery profiles was assessed in a randomized, crossover study involving 13 adult outpatients undergoing electroconvulsive therapy (ECT). Arterial blood pressure, heart rate, hemoglobin oxygen saturation, and electroencephalogram (EEG) activity were monitored during the ECT procedure. After premedication with glycopyrrolate, 0.2 mg intravenously (i.v.), and labetalol 20-30 mg i.v. hypnosis was induced with a bolus injection of either methohexital or propofol, 0.75 mg/kg. Muscle paralysis was achieved by administering succinylcholine, 1.4 mg/kg i.v. Ventilation was assisted using a face mask while administering 100% oxygen. Thereafter, an electrical stimulus was administered and the length of the resulting motor and EEG seizures was measured. Mood level and cognitive function were assessed prior to induction of anesthesia and after ECT. A total of 72 treatment sessions were evaluated. Each patient underwent a minimum of four treatments and received both induction drugs equally. Although the use of propofol was associated with significantly shorter motor and EEG seizure durations (mean +/- SEM) compared with methohexital (34 +/- 1.6 s and 52 +/- 2.9 s vs 39 +/- 1.5 s and 61 +/- 3.0 s, respectively), this difference was not clinically significant because the durations exceeded 30 s in both groups. Although awakening times were similar, both hemodynamic stability and cognitive recovery were more favorable after propofol. Compared with methohexital, the use of propofol was associated with a clinically insignificant decrease in seizure duration. However, propofol was associated with improved hemodynamic stability and an earlier return of cognitive function after ECT. PMID- 8010458 TI - The role of continuous background infusions in patient-controlled epidural analgesia for labor and delivery. AB - The use of a background infusion with intravenous patient-controlled analgesia (IV-PCA) increases drug consumption without any additional contribution to analgesia. There are no data on the potential advantage of a background infusion administered with patient-controlled epidural analgesia (PCEA) for labor and delivery. Sixty women were randomized to one of four groups and received either: (a) demand dose PCEA (demand dose = 3 mL; lockout interval = 10 min); (b) continuous infusion plus demand dose PCEA (two separate infusion rates: 3 mL/h and 6 mL/h); or (c) a fixed-rate continuous epidural infusion (CEI) at 12 mL/h. All patients received 0.125% bupivacaine with 2 micrograms/mL of fentanyl. The study protocol was double-blind and placebo-controlled. Visual analog pain scores, motor strength, and bilateral pinprick analgesia were assessed every half hour by a blinded observer. Pain scores, cephalad extent of sensory analgesia, and motor block were no different among the study groups during the first and second stages of labor. Cumulative hourly bupivacaine use was similar among all PCEA study groups. However, use of PCEA (in whatever mode) provided a 35% dose sparing effect in comparison to CEI. The PCEA groups receiving no background infusion or a 3-mL/h background infusion had a greater need for physician administered supplemental bupivacaine during the first stage of labor. While not statistically significant, a trend toward increased need for supplementation was seen in these same patient groups over the entire course of labor and delivery.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8010459 TI - Intraoperative combined administration of indomethacin and buprenorphine suppositories as prophylactic therapy for post-open-cholecystectomy pain. AB - Buprenorphine and indomethacin are quite different pharmacologically. The objective of this study was to determine the analgesic effect from their combined administration in suppository form. Eighty patients undergoing open cholecystectomy under nitrous oxide-oxygen-sevoflurane anesthesia, in addition to epidural anesthesia using lidocaine, were divided into four groups: Group A received buprenorphine 0.4 mg and indomethacin 50 mg; Group B, buprenorphine 0.4 mg; Group C, indomethacin 50 mg; and Group D, no drug. The drugs were administered after induction of general anesthesia. One patient was withdrawn because of the administration of the wrong drug. Patients in Group A required fewer analgesics, had a longer period of analgesic effect from the end of surgery, and enjoyed a better pain score. This group also included more patients who required no analgesics. We conclude that the combined administration of opioid and nonopioid suppositories may provide far better prophylactic analgesia than a single drug. PMID- 8010460 TI - Postoperative epidural analgesia and oral anticoagulant therapy. AB - The relative safety of epidural catheter placement with subsequent heparinization has been well documented. However, what is the risk of neurologic sequelae in such patients who receive warfarin perioperatively? This study retrospectively evaluates the risk of spinal hematoma in patients receiving postoperative epidural analgesia while receiving low-dose warfarin after total knee replacement. All patients received low-dose warfarin to prolong the prothrombin time (PT) to 15.0-17.3 s (normal 10.9-12.8 s). There were 192 epidural catheters placed in 188 patients. All catheters were advanced through an 18-gauge needle. In 13 instances, blood was noted during needle and/or catheter placement. In addition to warfarin, 36 patients with indwelling catheters received nonsteroidal antiinflammatory drugs (NSAIDs). Epidural catheters were left indwelling 37.5 +/- 15 h (range 13-96 h). The mean PT was not increased beyond the normal range until the third postoperative day and did not reach 15 s until the seventh postoperative day. Cumulative warfarin dose at that time was 20.0 +/- 7.6 mg. Mean PT at the time of epidural catheter removal was 13.4 +/- 2 s. There were no signs of spinal hematoma. Although epidural catheter placement and subsequent anticoagulation with warfarin appears relatively safe, there is a large variability in patient response to warfarin; therefore, coagulation status should be monitored to avoid excessive prolongation of the PT, and the patient should be watched closely for evidence of spinal hematoma. PMID- 8010461 TI - Comparison of high-dose thrombin time with activated clotting time for monitoring of anticoagulant effects of heparin in cardiac surgical patients. AB - The activated clotting time (ACT) is routinely used for monitoring of heparin effects during cardiopulmonary bypass (CPB). However, ACT is not a specific assay for heparin and may be influenced by several other factors, which may be misleading with regard to the proper administration of heparin and protamine. In this pilot study, we compared a new test, the high-dose thrombin time (HiTT), with the conventional ACT test for both in vitro and in vivo heparin-induced anticoagulation. Our in vitro results showed that there were heparin dose dependent increases in ACT and HiTT. Data on 30 adult cardiac patients indicated that HiTT correlated well with heparin concentration both after initial heparin administration and during CPB (r = 0.645 and 0.515). Hypothermia and hemodilution occurring during CPB did not alter HiTT results. ACT also correlated well with both heparin concentration and HiTT before CPB, but the linear relationship was lost during CPB. Our results suggest that HiTT is a useful assay for monitoring heparin effects during cardiac surgery, even during hypothermia and hemodilution. PMID- 8010462 TI - Systemic opioids enhance the spread of sensory analgesia produced by intrathecal lidocaine. AB - The effect of different doses of fentanyl and nalbuphine on the spread of spinal analgesia produced by lidocaine was studied in 68 patients undergoing transurethral resection of the prostate (TURP) under spinal anesthesia. Patients were randomly assigned to six groups: fentanyl A, B, or C (FA, FB, FC) or nalbuphine A, B, or C (NA, NB, NC), which received intravenous (i.v.) 50, 100, or 150 micrograms of fentanyl or 10, 15, or 20 mg of nalbuphine, respectively, 20 min after spinal anesthesia with lidocaine. We tested the level of spinal analgesia with pinprick sensation 20 min after spinal anesthesia and 10 min after the opioid administration, when 0.4 mg of naloxone was administered i.v. The levels of sensory analgesia were reassessed 10 min after naloxone. Ten minutes after fentanyl or nalbuphine, the level of analgesia increased (1.8 +/- 1.7, 3.1 +/- 1.2, and 4.1 +/- 1.5 cm, in the FA, FB, and FC groups and 1.9 +/- 0.9, 2.6 +/ 1.4, and 3.7 +/- 2.2 cm in the NA, NB, and NC groups, respectively). The increases in the level of analgesia differed significantly between the fentanyl groups (F = 8.0939; df = 2.35; P < 0.001), the increase produced by 150 micrograms being significantly higher than produced by 50 micrograms of fentanyl (limits of confidence -4.236809 and -0.4431909; P < 0.01). Naloxone reversed the effect of fentanyl and 10 min after its administration the fentanyl groups did not differ with regard to the level of spinal analgesia.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8010463 TI - Epidural droperidol reduces the side effects and duration of analgesia of epidural sufentanil. AB - The postoperative combination of epidural sufentanil and epidural droperidol was assessed in 40 patients with hip or knee arthroplasties. Patients were given a single intravenous (i.v.) bolus of sufentanil 50 micrograms with either droperidol 2.5 mg or placebo (0.9% NaCl) epidurally in a double-blind, randomized design at the first request for postoperative analgesia. Pain scores, side effects, and sufentanil plasma concentrations were regularly assessed for 5 h after injection. Heat pain thresholds were measured pre- and postoperatively. The incidence of nausea, emesis, and pruritus associated with epidural sufentanil was decreased by epidural droperidol (P < 0.01, P < 0.001, P < 0.05, respectively). More patients were sedated with epidural droperidol than with placebo (P < 0.02). The initial reduction in pain scores was similarly profound, but the duration of analgesia after sufentanil and droperidol was significantly shorter than after sufentanil and placebo (P < 0.02). Phasic and tonic heat pain thresholds were increased postoperatively 1 h after sufentanil and placebo (P < 0.01 and P < 0.0005, respectively). Only the tonic heat pain thresholds were increased 1 h after sufentanil and droperidol (P < 0.002). The addition of epidural droperidol significantly reduced the excitatory side effects of epidural sufentanil while diminishing the duration of analgesia. These interactions may be of clinical significance in reducing the toxicity of opioids, but the effect on duration of analgesia must be considered when repeated doses of opioids are prescribed. PMID- 8010464 TI - Epidural analgesia and the incidence of cesarean section. Time for a closer look. PMID- 8010465 TI - Does early administration of epidural analgesia affect obstetric outcome in nulliparous women who are receiving intravenous oxytocin? AB - BACKGROUND: Some studies suggest that epidural analgesia prolongs labor and increases the incidence of cesarean section, especially if it is administered before 5 cm cervical dilation. The purpose of the current study was to determine whether early administration of epidural analgesia affects obstetric outcome in nulliparous women who are receiving intravenous oxytocin. METHODS: Informed consent was obtained from healthy nulliparous women with a singleton fetus in a vertex presentation, who requested epidural analgesia while receiving intravenous oxytocin at at least 36 weeks' gestation. Each patient was randomized to receive either early or late epidural analgesia. Randomization occurred only after the following conditions were met: (1) the patient requested pain relief at that moment, (2) a lumbar epidural catheter had been placed, and (3) the cervix was at least 3 but less than 5 cm dilated. Patients in the early group immediately received epidural bupivacaine analgesia. Patients in the late group received 10 mg nalbuphine intravenously. Late-group patients did not receive epidural analgesia until they achieved a cervical dilation of at least 5 cm or until at least 1 h had elapsed after a second dose of nalbuphine. RESULTS: Early administration of epidural analgesia did not prolong the interval between randomization and the diagnosis of complete cervical dilation, and it did not increase the incidence of malposition of the vertex at delivery. Also, early administration of epidural analgesia did not result in an increased incidence of cesarean section or instrumental vaginal delivery. Thirteen (18%) of 74 women in the early group and 14 (19%) of 75 women in the late group underwent cesarean section (relative risk for the early group 0.94; 95% confidence interval 0.48 1.84). Patients in the early group had lower pain scores between 30 and 120 min after randomization, and were more likely to experience transient hypotension. Infants in the late group had lower umbilical arterial and venous blood pH and higher umbilical arterial and venous blood carbon dioxide tension measurements at delivery. CONCLUSIONS: Early administration of epidural analgesia did not prolong labor or increase the incidence of operative delivery, when compared with intravenous nalbuphine followed by late administration of epidural analgesia, in nulliparous women who were receiving intravenous oxytocin. PMID- 8010467 TI - Intrathecal sufentanil compared to epidural bupivacaine for labor analgesia. AB - BACKGROUND: Although intrathecal sufentanil has been reported to provide rapid onset, complete analgesia lasting 1-3 h for the first stage of labor, no well controlled double-blind study has compared this technique to the use of epidurally administered local anesthetics. METHODS: Fifty healthy parturient women requesting labor analgesia were studied. In a combined spinal-epidural technique, a spinal needle was inserted through the epidural needle before insertion of the epidural catheter. Patients were randomly assigned to receive either intrathecal sufentanil (10 micrograms) and epidural saline, or intrathecal saline and epidural bupivacaine (30 mg). Visual analog scores for pain, blood pressure, heart rate, sensory levels, and the incidence of nausea, pruritus, and motor blockade were recorded. RESULTS: Patients receiving intrathecal sufentanil had significantly lower visual analog pain scores at 5, 15, and 30 min after injection and a greater duration of analgesia before requesting additional medication (mean 123 vs. 68 min for those receiving bupivacaine; P < 0.05). These patients also experienced pruritus more frequently but motor blockade less frequently than patients receiving epidural bupivacaine. The groups exhibited dermatomal sensory deficits to pin prick as well as bradycardia and hypotension with equal frequency. The length of labor and type of delivery were similar between the groups. No patient experienced a post-dural puncture headache. CONCLUSIONS: The rapid onset of analgesia and lack of motor blockade from intrathecal sufentanil injection may be advantageous in certain clinical situations. With this technique, however, pruritus is common; hypotension may occur; and extensive dermatomal spread suggests that early-onset respiratory depression could occur. Therefore, blood pressure and respiratory adequacy should be monitored if intrathecal sufentanil is used. PMID- 8010466 TI - Does early administration of epidural analgesia affect obstetric outcome in nulliparous women who are in spontaneous labor? AB - BACKGROUND: Some studies suggest that epidural analgesia prolongs labor and increases the incidence of cesarean section, especially if it is administered before 5 cm cervical dilation. The purpose of the current study was to determine whether early administration of epidural analgesia affects obstetric outcome in nulliparous women who are in spontaneous labor. METHODS: Informed consent was obtained from 344 healthy nulliparous women with a singleton fetus in a vertex presentation, who requested epidural analgesia during spontaneous labor at at least 36 weeks' gestation. Each patient was randomized to receive either early or late epidural analgesia. Randomization occurred only after the following conditions were met: (1) the patient requested pain relief at that moment, (2) a lumbar epidural catheter had been placed, and (3) the cervix was at least 3 cm but less than 5 cm dilated. Patients in the early group immediately received epidural bupivacaine analgesia. Patients in the late group received 10 mg nalbuphine intravenously. Late-group patients did not receive epidural analgesia until they achieved a cervical dilation of at least 5 cm or until at least 1 h had elapsed after a second dose of nalbuphine. Ten of the 344 patients were excluded because of a protocol violation or voluntary withdrawal from the study. RESULTS: Early administration of epidural analgesia did not increase the incidence of oxytocin augmentation, prolong the interval between randomization and the diagnosis of complete cervical dilation, or increase the incidence of malposition of the vertex at delivery. Also, early administration of epidural analgesia did not result in an increased incidence of cesarean section or instrumental vaginal delivery. Seventeen (10%) of 172 women in the early group and 13 (8%) of 162 women in the late group underwent cesarean section (relative risk for the early group 1.22; 95% confidence interval 0.62-2.40). Patients in the early group had lower pain scores between 30 and 150 min after randomization. Infants in the late group had lower umbilical arterial and venous blood pH and higher umbilical venous blood carbon dioxide tension measurements at delivery. CONCLUSIONS: Early administration of epidural analgesia did not prolong labor, increase the incidence of oxytocin augmentation, or increase the incidence of operative delivery, when compared with intravenous nalbuphine followed by late administration of epidural analgesia, in nulliparous women who were in spontaneous labor at term. PMID- 8010468 TI - Masseter muscle rigidity and malignant hyperthermia susceptibility in pediatric patients. An update on management and diagnosis. AB - BACKGROUND: Controversy exists regarding the definition of masseter muscle rigidity (MMR) and anesthetic management after MMR. This study reports current anesthetic management after MMR, estimates the incidence of clinical malignant hyperthermia (MH) in patients with MMR, and is the first to evaluate the coincidence of MMR with malignant hyperthermia susceptibility (MHS) according to the 1987 North American Malignant Hyperthermia Group protocol. METHODS: Practicing anesthesiologists referred pediatric patients for biopsy between 1986 and 1991 based on evidence of MMR after succinylcholine (1975-1991). The clinical scenario was described as MMR alone or MMR followed by signs of MH, including arterial CO2 tension > 50 mmHg, arterial pH < or = 7.25, and base deficit > 8. Patients had caffeine-halothane muscle contracture testing to determine MHS. RESULTS: Seventy patients (50 boys and 20 girls) were evaluated. Eighty-three percent (58 of 70) of anesthetics were halothane-succinylcholine. In 68% (48 of 70) of cases, the anesthetic was discontinued, whereas anesthesia was continued with nontriggering agents in 11% (8 of 70) and with triggering agents in 13% (9 of 70). Fifty-nine percent (41 of 70) of patients were diagnosed as MHS by muscle biopsy. In 7% (5 of 70) of patients, clinical MH developed within 10 min of MMR. CONCLUSIONS: This study, by using the current North American Malignant Hyperthermia Group protocol, reaffirms the high incidence (59%, 41 of 70) of MHS associated with MMR as confirmed by muscle biopsy. Of the MHS patients, 5 developed signs of clinical MH. Most anesthesiologists in this study, when confronted with MMR, discontinued anesthesia. Because of the potential lethality of MH and the > 50% concordance between MMR and MHS, the most conservative course of action after MMR is to discontinue the anesthetic and observe the patient for clinical evidence of MH. An acceptable alternative, depending on the urgency of the surgery, would be to continue anesthesia with nontriggering agents for MH, with appropriate monitoring. PMID- 8010469 TI - Is postoperative intrathecal catheter use associated with central nervous system infection? AB - BACKGROUND: Continuation of intrathecal anesthesia into the postoperative period has been limited by important safety concerns. Principal among these has been the assumption that extended intrathecal therapy leads to spinal (epidural and intrathecal) space infections. To address the role of extended intrathecal catheter therapy as a cause of infections, we cultured all intrathecal catheters used to provide postoperative analgesia. METHODS: All intrathecal catheters were inserted in the operating room using sterile technique. The catheters were used either for the duration of the patients stay in the intensive care unit or until they were no longer judged to provide a therapeutic advantage. They were removed without skin preparation. The distal 2-3 cm of the catheters was cultured using semiquantitative culture methods. Results were divided into four groups: group 1, negative culture results; group 2, ten or fewer colonies of growth; group 3, more than 10 colonies on initial plates and/or growth from broth cultures; and group 4, any bacterial growth, along with evidence of local or central nervous system infections. RESULTS: Cultures were obtained from 139 patients with a mean indwelling catheter time of 66.1 h. Group 1 (102 patients) had a mean indwelling duration of 55 h. Group 2 (26 patients) and group 3 (11 patients) had significantly longer indwelling duration (83.2 h P = .0023, 129.6 h P = < .0001, respectively) than group 1. Cultures of cerebrospinal fluid obtained simultaneously with catheter cultures in 9 cases (5 in group 2 and 4 in group 3) showed no growth. No patient had evidence of local or central nervous system infection. Difficulty of catheter placement (number of attempts made and the number of levels explored), antibiotic administration, the composition of the postoperative infusions and the number of catheter breaks in the postoperative period were similar in each group. With the exception of two catheters in group 3, (cultured at 49 and 54 h), significant bacterial growth (more than ten colonies) was observed only after more than 96 h of indwelling duration. CONCLUSIONS: Application of semiquantitative culture methods assisted in explaining the results seen in group 2 as secondary to contamination of the catheter that occurred on removal. Higher numbers of bacteria (group 3) may define a population at increased risk for infectious complications. The results of this study do not absolutely resolve the issue of infectious risk associated with postoperative intrathecal catheter use, nor do they define a safe period beyond which the risk of continued catheter use would be unacceptable. However, it appears that limited periods of use (96 h or less) is not associated with either frequent local or spinal infections. Semiquantitative culture methods may help identify individuals (with catheter cultures yielding more than ten colonies) at increased risk for infectious complications and in need of closer observation. PMID- 8010470 TI - Pharmacokinetics and pharmacodynamics of rocuronium in patients with cirrhosis. AB - BACKGROUND: Rocuronium, like other steroidal nondepolarizing muscle relaxants, may in part be eliminated by the liver. To determine the influence of liver disease on its neuromuscular blocking effect, we studied the pharmacokinetics and pharmacodynamics of rocuronium in patients with cirrhosis. METHODS: Eighteen patients undergoing elective surgery, 10 with cirrhosis and 8 with normal liver function, were studied. Anesthesia was induced with intravenous thiopental 5-7 mg.kg-1 and maintained with 60% nitrous oxide in oxygen and repeated doses of fentanyl 2 micrograms.kg-1. The force of thumb adduction in response to supramaximal ulnar nerve stimulation was monitored and recorded. An intravenous bolus of rocuronium 0.6 mg.kg-1 was administered and venous blood sampled at frequent intervals for 6 h. Plasma concentrations of rocuronium was measured by high-pressure liquid chromatography. Data were fitted to both a pharmacokinetic and a pharmacodynamic model by using a two-compartment open model and an effect compartment model. Data were analyzed by least-squares regression. RESULTS: The onset of neuromuscular blockade was longer (P < 0.01) in patients with cirrhosis (158 +/- 56 s) than in normal patients (108 +/- 33 s). Recovery of the thumb twitch to 75 and 90% of its control value was 77 +/- 25 and 88 +/- 29 min in cirrhotic patients versus 57 +/- 11 and 64 +/- 13 min, respectively, in normal patients (P < 0.05). The central volume of distribution of rocuronium was 104 +/- 21 in cirrhotic patients and 78 +/- 24 ml.kg-1 in normal patients (P < 0.05). No significant difference in elimination kinetics was observed between the two groups. The elimination half-life was 87.5 +/- 17.5 min in normal patients and 96.0 +/- 36.8 min in cirrhotic patients (difference not significant). This increased onset time was linearly correlated to the increased central volume of distribution of rocuronium in cirrhosis. CONCLUSION: Rocuronium onset time is longer in cirrhotic patients than in those with normal liver function; this can be explained by an increase in the volume in which rocuronium initially distributes. Although elimination kinetics are unchanged in patients with cirrhosis, rocuronium recovery time is prolonged in cirrhotic patients. PMID- 8010471 TI - Neonatal resuscitation using the laryngeal mask airway. AB - BACKGROUND: For a newborn requiring positive-pressure ventilation (PPV), the American Heart Association recommends bag-and-mask ventilation, a challenging procedure for those inexperienced in neonatal resuscitation. The objective of this prospective study was to evaluate the laryngeal mask airway (LMA) as an alternative method of airway management in neonates requiring PPV at birth. METHODS: With the approval of the institutional ethics committee, consent was obtained from women in labor at a tertiary care-perinatal center. Inclusion criteria consisted of an expected birth weight of at least 2.5 kg, gestational age of at least 35 weeks, and resuscitation requiring PPV. Neonates meeting these criteria were resuscitated with PPV by means of the LMA. The ease of insertion, number of attempts required, time to establish effective ventilation, skin color, heart rate, respiratory effort, and Apgar scores were recorded. RESULTS: Attendance by the investigators at delivery was achieved in 93 cases, with 21 meeting the inclusion criteria. In all cases, the LMA was successfully inserted on the first attempt and provided a clinically patent airway. Twenty neonates were successfully resuscitated with the LMA to provide PPV, with no complications directly attributable to its use. One neonate required LMA removal and tracheal intubation to facilitate administration of epinephrine; data from this case was removed from the study. CONCLUSIONS: Providing PPV at birth via a size-1 LMA is effective and easily learned by personnel with expertise in neonatal resuscitation. The LMA should be further assessed as an alternative to bag-and mask ventilation for this purpose. PMID- 8010472 TI - Inhaled nitric oxide reverses the increase in pulmonary vascular resistance induced by permissive hypercapnia in patients with acute respiratory distress syndrome. AB - BACKGROUND: The aim of this prospective study was to determine if inhaled nitric oxide (NO) would reverse the increase in pulmonary arterial pressures and in pulmonary vascular resistance induced by acute permissive hypercapnia in patients with acute respiratory distress syndrome. METHODS: In 11 critically ill patients (mean age 59 +/- 22 yr) with acute respiratory distress syndrome (Murray Score > or = 2.5), the lungs were mechanically ventilated with NO 2 ppm during both normocapnic and hypercapnic conditions. Four phases were studied: normocapnia (arterial carbon dioxide tension 38 +/- 6 mmHg, tidal volume (655 +/- 132 ml); normocapnia plus inhaled NO 2 ppm; hypercapnia (arterial carbon dioxide tension 65 +/- 15 mmHg, tidal volume 330 +/- 93 ml); and hypercapnia plus inhaled NO 2 ppm. Continuous recordings were made of heart rate, arterial pressure, pulmonary artery pressure, tracheal pressure, and tidal volume (by pneumotachograph). At the end of each condition, arterial pressure, pulmonary artery pressure, cardiac filling pressures, and cardiac output were measured. Simultaneous arterial and mixed venous blood samples were obtained to measure arterial oxygen tension, arterial carbon dioxide tension, mixed venous oxygen tension, arterial hemoglobin oxygen saturation, mixed venous hemoglobin oxygen saturation, pH, and blood hemoglobin and methemoglobin concentrations (by hemoximeter). In addition, plasma concentrations of catecholamines were measured with a radioenzymatic assay. In 5 patients, end-tidal carbon dioxide tension was measured with a nonaspirative infrared capnometer. Calculations were made of pulmonary vascular resistance index, systemic vascular resistance index, true pulmonary shunt, and alveolar dead space. RESULTS: During hypercapnia, NO decreased pulmonary vascular resistance index from 525 +/- 223 to 393 +/- 142 dyn.s.cm-5.m-2 (P < 0.01), a value similar to that measured in normocapnic conditions (391 +/- 122 dyn.s.cm 5.m-2). It also reduced mean pulmonary artery pressure from 40 +/- 9 to 35 +/- 8 mmHg (P < 0.01). NO increased arterial oxygen tension (inspired oxygen fraction 1) from 184 +/- 67 to 270 +/- 87 mmHg during normocapnia and from 189 +/- 73 to 258 +/- 101 mmHg during hypercapnia (P < 0.01). NO decreased true pulmonary shunt during normocapnia (from 34 +/- 3% to 28 +/- 4%, P < 0.001) but had no significant effect on it during hypercapnia (39 +/- 7% vs. 38 +/- 8.5%). In five patients, NO resulted in a decrease in alveolar dead space from 34 +/- 7% to 28 +/- 10% in normocapnic conditions and from 30 +/- 9% to 22 +/- 10% in hypercapnic conditions (P < 0.05). CONCLUSIONS: Inhaled NO completely reversed the increase in pulmonary vascular resistance index induced by acute permissive hypercapnia. It only partially reduced the pulmonary hypertension induced by acute permissive hypercapnia, probably because the flow component of the increase in pulmonary pressure (i.e., the increase in cardiac output) was not reduced by inhaled NO. A significant increase in arterial oxygenation after NO administration was observed during normocapnic and hypercapnic conditions. A ventilation strategy combining permissive hypercapnia and inhaled NO may reduce the potentially deleterious effects that permissive hypercapnia alone has on lung parenchyma and pulmonary circulation. PMID- 8010473 TI - Meperidine for patient-controlled analgesia after cesarean section. Intravenous versus epidural administration. AB - BACKGROUND: Although meperidine has been used for patient-controlled analgesia both intravenously (PCIA) and epidurally (PCEA), these routes have not been compared, and many studies have suggested that there is no advantage to the epidural route for administration of lipophilic opioids. METHODS: A randomized, double-blind, crossover study was conducted for 24 h after cesarean section to compare the analgesic efficacy, side effects, patient satisfaction, drug use, and plasma drug concentrations with meperidine administered either as PCIA or as PCEA. Two groups, stratified for time of cesarean section during epidural anesthesia, postoperatively received either PCEA (group 1) or PCIA (group 2) with identical variables for 12 h before crossing to the other route for an additional 12 h. RESULTS: Results from 45 patients showed a similar speed of analgesic onset but, subsequently, significantly lower pain scores both at rest and with coughing in those receiving PCEA (P = 0.0001). Nausea and pruritus scores did not differ between the groups in the first 12 h postoperatively, but sedation scores were significantly higher with PCIA (P = 0.0001). Patient satisfaction scores and preference significantly favored PCEA (P = 0.0001), with almost 90% of participants preferring the epidural route. Meperidine use was reduced approximately 50% with PCEA (P = 0.0001), and plasma meperidine and normeperidine concentrations were significantly lower (P = 0.0001). CONCLUSIONS: We conclude that after cesarean section, PCEA with meperidine produces high-quality pain relief with few side effects and has significant advantages over PCIA meperidine. With the caveat that neonatal effects in breast-feeding mothers have yet to be evaluated, it can be highly recommended in this population. PMID- 8010474 TI - Evaluation of intravenous ketorolac administered by bolus or infusion for treatment of postoperative pain. A double-blind, placebo-controlled, multicenter study. AB - BACKGROUND: Ketorolac is a nonsteroidal analgesic that may provide postoperative analgesia without opioid-related side effects. This double-blind, randomized, multicenter study evaluated the analgesic efficacy and safety of intravenous ketorolac in 207 patients during the first 24 h after major surgery. METHODS: Subjects were assigned to receive one of three analgesic regimens: a ketorolac infusion, ketorolac boluses, or placebo. All subjects had access to intravenous morphine via patient-controlled analgesia (PCA). Evaluations included PCA morphine used, pain assessment (categorical pain intensity scores and visual analogue pain scores), pain relief (categorical pain relief scores), sedation, presence of adverse events, and overall rating of regimens by study observers and patients. RESULTS: Patients in the ketorolac infusion group (but not the ketorolac bolus group) used less morphine (average 33 mg) than did the placebo group (44 mg) (P = 0.009). Significant differences favoring both ketorolac groups were seen in the pain intensity and the categorical pain relief scores at various time points during the study. At the termination of the study, compared with the placebo group, categorical pain intensity scores were lower in the ketorolac bolus group; visual analogue pain scores were lower in both ketorolac groups; and pain relief scores were higher in the ketorolac bolus group. The incidence of vomiting was significantly greater in the placebo group (27%) than in the ketorolac infusion group (12%) or bolus group (9%) (P = 0.032 and P = 0.005, respectively). The incidence of postoperative fever was 10% in the ketorolac bolus group and 25% in the placebo group (P = 0.013). Study observers noted less nursing difficulty while caring for patients in the ketorolac infusion group (P = 0.015). Study observers and patients in both ketorolac groups reported statistically significant overall drug superiority compared with placebo. CONCLUSIONS: It is concluded that intravenous boluses or infusions of ketorolac in conjunction with PCA morphine provide effective, safe analgesia after major surgery and improve on the response to PCA morphine alone. PMID- 8010475 TI - Genetic effects on the variability of the halothane and caffeine muscle contracture tests. AB - BACKGROUND: The spectrum of the clinical presentation of malignant hyperthermia (MH) and the results of recent linkage studies suggest that there is a degree of heterogeneity in MH susceptibility. In the current study, we analyzed in vitro muscle contracture tests from members of large families with MH to evaluate if the results of these tests could be related to genetic influences. METHODS: Forty seven subjects from four families with an MH-related death and with at least five clinically MH-susceptible individuals per family, as diagnosed by an in vitro muscle contracture test according to the protocol of the European MH Group, were included in the current analysis. We compared the strength of muscle contractures to challenges of halothane, caffeine, or both and the effect of these two drugs on twitch potentiation in response to supramaximal electrical stimulation among the families. RESULTS: Clinical MH susceptibility was confirmed in 36 individuals, and 11 individuals were diagnosed as MH-negative. In MH-susceptible individuals, muscle contractures to the 2% halothane challenge were significantly higher in family 1 (n = 15; 16.2 +/- 2.9 mN, mean +/- standard error of the mean) and in family 4 (n = 5; 16.4 +/- 5 mN) than in family 2 (n = 9; 5.8 +/- 1.5 mN) or family 3 (n = 7; 6.0 +/- 1.1 mN). Muscle contractures to the caffeine challenge (2 mM) were significantly increased in family 1 (7.3 +/- 1.4 mN) compared with those in family 3 (1.3 +/- 1.0 mN). In addition, we found a dose dependent twitch potentiation to the halothane challenge in family 2 (P < 0.01) and to the caffeine challenge in families 2 (P < 0.001) and 3 (P < 0.01), whereas there was no twitch potentiation in families 1 and 4. CONCLUSIONS: The differences of in vitro muscle contracture tests among several families with MH provide evidence for genetic influences on the variability of this test procedure. However, it is not known if the observed differences are caused by heterogeneity of the MH gene mutation(s) or by other genetic factors that might modify muscle contractures in vitro. PMID- 8010476 TI - The pharmacokinetics and pharmacodynamics of the stereoisomers of mivacurium in patients receiving nitrous oxide/opioid/barbiturate anesthesia. AB - BACKGROUND: Mivacurium consists of a mixture of three stereoisomers: cis-trans (34-40%), trans-trans (52-60%), and cis-cis (4-8%). These isomers differ in potency (the trans-trans and the cis-trans isomers are equipotent and the cis-cis isomer is 1/13th as potent a neuromuscular blocking agent) and in rates of in vitro hydrolysis (in vitro half-lives are less than 2 min for the cis-trans and trans-trans isomers and 276 min for the cis-cis isomer). The current study was undertaken to determine the pharmacokinetic profile of the individual stereoisomers of mivacurium, to evaluate the dose-proportionality of the more potent trans-trans and cis-trans isomers, and to evaluate the pharmacodynamics of mivacurium in healthy adult patients receiving a consecutive two-step infusion of mivacurium. METHODS: Eighteen ASA physical status 1 or 2 adult male patients undergoing elective surgery under nitrous oxide/oxygen/fentanyl anesthesia were studied. Neuromuscular function was monitored using a mechanomyograph at a frequency of 0.15 Hz. An infusion of mivacurium was begun at 5 micrograms.kg 1.min-1. Sixty minutes later, the infusion rate was doubled to 10 micrograms.kg 1.min-1, and, 60 min after that, the infusion was discontinued. All patients were allowed to recover spontaneously from mivacurium-induced neuromuscular block. Venous blood samples were drawn for the determination of the plasma concentrations of each isomer of mivacurium by a stereospecific high performance liquid chromatographic method. Pharmacokinetic parameters were determined using noncompartmental analysis. RESULTS: During the 5-micrograms.kg-1.min-1 infusion, patients developed 83.2 +/- 13.6% neuromuscular block. Increasing the infusion to 10 micrograms.kg-1.min-1 increased the depth of block to 99.0 +/- 2.0%. After discontinuation of the infusion, patients returned to 25% of their baseline muscle strength in 9.3 +/- 3.7 min and had 25-75% and 5-95% recovery indexes of 7.2 +/- 1.8 and 16.8 +/- 3.7 min, respectively. The volumes of distribution (V beta) of the cis-trans, trans-trans, and cis-cis isomers were 0.29 +/- 0.24, 0.15 +/- 0.05, and 0.34 +/- 0.08 l/kg, respectively. During the 5-micrograms.kg-1.min 1 infusion, the steady-state clearances of the potent cis-trans and trans-trans isomers were 106 +/- 67 and 63 +/- 34 ml.min-1.kg-1, respectively; the clearance of the less potent cis-cis isomer was 4.6 +/- 1.1 ml.min-1.kg-1. The elimination half-lives of the cis-trans and trans-trans isomers were 1.8 +/- 1.1 and 1.9 +/- 0.7 min, respectively, and that of the cis-cis isomer was 52.9 +/- 19.8 min. Clearance of the cis-trans and trans-trans isomers did not vary with infusion rate. CONCLUSIONS: The short elimination half-lives and high metabolic clearances of the potent cis-trans and trans-trans isomers are consistent with the short duration of action of mivacurium. The cis-cis isomer does not appear to produce significant neuromuscular block as evident by the return of twitch height to baseline despite persistent cis-cis isomer concentrations. PMID- 8010478 TI - Time-dependent effect of morphine and time-independent effect of MK-801, an NMDA antagonist, on the thermal hyperesthesia induced by unilateral constriction injury to the sciatic nerve in the rat. AB - BACKGROUND: It is known that peripheral nerve injury induces time-dependent changes in dorsal horn function. The current study investigated the time dependency of the effects of intrathecal morphine and MK-801, an N-methyl-D aspartate antagonist, on the thermal hyperesthesia evoked by unilateral constriction injury to the sciatic nerve in the rat. METHODS: In rats with a unilateral constriction injury to the sciatic nerve, paw withdrawal latency against thermal stimulation for the injured paw was typically 3 s less than that for the uninjured paw during the first 5 weeks after the injury. Drugs were administered intrathecally 1 or 5 weeks after the nerve injury. RESULTS: Intrathecal morphine increased the paw withdrawal latencies of both the injured paw and the uninjured paw in an equally dose dependent manner in the 1-week study. In the 5-week study, morphine increased the paw withdrawal latency of the uninjured paw in a dose-dependent manner, but not that of the injured paw. Intrathecal MK-801 increased the paw withdrawal latency of the injured paw to the level of the uninjured paw in a dose-dependent manner in both the 1- and 5-week studies. CONCLUSIONS: These data indicate that (1) an N-methyl-D-aspartate receptor-mediated spinal facilitation may be the common mechanism maintaining the thermal hyperesthesia evoked by the constriction injury, and (2) the effects of intrathecal morphine on this thermal hyperesthesia are time-dependent. PMID- 8010477 TI - Effects of morphine and physostigmine on the ventilatory response to carbon dioxide. AB - BACKGROUND: It has been reported that physostigmine antagonizes morphine-induced respiratory depression, but it is not known whether this is due to a central chemoreceptor effect, an effect on the peripheral chemoreflex loop, or both. We therefore assessed the effect of morphine and physostigmine on the normoxic hypercapnic ventilatory response mediated by the central and peripheral chemoreceptors in ten alpha-chloralose-urethan-anesthetized cats. METHODS: The breath-by-breath ventilatory responses to stepwise changes in end-tidal CO2 tension were determined before (control), after administration of morphine hydrochloride (0.15 mg.kg-1) and during intravenous infusion of physostigmine salicylate (bolus of 0.05 mg.kg-1 followed by 0.025 mg.kg-1.h-1). Each response was separated into a central and a peripheral chemoreflex characterized by CO2 sensitivity (Sc and Sp), time constant, time delay, and apneic threshold (a single off-set B). RESULTS: Morphine increased B and decreased Sc and Sp (P < 0.01), but not the ratio Sp/Sc. Subsequent infusion of physostigmine decreased B (P < 0.01), without further change of Sp and Sc. Premedication with physostigmine decreased B, Sp and Sc (P < 0.01) vs. control, but not Sp/Sc. Subsequent administration of morphine decreased Sp and Sc further but increased B (P < 0.01), while Sp/Sc remained constant. CONCLUSIONS: Because morphine diminishes the Sc and Sp of the chemoreflex loop to the same extent this depressant effect is presumably due to an action on the respiratory integrating centers rather than on the peripheral and central chemoreceptors as such and is not antagonized by physostigmine. We argue that the increase in B may be due to changes in the amount of acetylcholine available in the brain and can be antagonized by physostigmine. PMID- 8010481 TI - Local anesthetics depress the calcium current of rat sensory neurons in culture. AB - BACKGROUND: Local anesthetics are known to inhibit the voltage-gated sodium current (INa) of the nerve membrane, but it has not been fully studied whether anesthetic concentrations of local anesthetics depress the voltage-gated calcium current (ICa) of mammalian neurons. The effects of local anesthetics on ICa evoked in cultured rat dorsal root ganglion cells were studied. METHODS: Whole cell patch clamp recordings were made from rat dorsal root ganglion cells cultured for 1-3 weeks. ICa was recorded using patch electrodes filled with Cs aspartate in Na(+)-free external solution containing 5 mM-Ba2+. All drugs, including local anesthetics, were applied by miniperfusion from micropipettes by pressure ejection. RESULTS: Tetracaine (300 microM) depressed the peak amplitudes of high voltage-activated (HVA)-ICa to 22.6 +/- 8.8% of control values (n = 14) without affecting the current-voltage relation. A tetracaine dose-response curve for HVA-ICa indicated an apparent dissociation constant of 79.5 microM. Tetracaine (30 microM) depressed nicardipine-sensitive HVA-I(Ca) (L-type) to 14.3 +/- 6.7% (n = 6), omega-conotoxin-sensitive HVA-ICa (N-type) to 81.6 +/- 9.6% (n = 7), and low voltage-activated (LVA)-ICa (T-type) to 65.1 +/- 11.1% (n = 6) of their respective controls. Local anesthetics other than tetracaine also depressed HVA-ICa but were of different potency; the rank sequence was dibucaine > tetracaine > bupivacaine >> procaine = lidocaine. CONCLUSIONS: These results suggest that both HVA-ICa and LVA-ICa are depressed by tetracaine used at the concentrations required for spinal anesthesia and that the L-type Ca2+ channel among Ca2+ channel subtypes is the most susceptible to tetracaine. A good correlation between local anesthetic potencies to inhibit HVA-ICa and their anesthetic potencies implies that the inhibition of calcium influx through voltage-gated channels may contribute to spinal anesthetic mechanisms. PMID- 8010480 TI - Differential effects of halothane and isoflurane on contractile force and calcium transients in cardiac Purkinje fibers. AB - BACKGROUND: Halothane and isoflurane have been shown to differentially effect mechanisms of contraction in working myocardial fibers. The aim of this study was to compare effects of halothane and isoflurane on contractile force (CF) and Ca2+ transients in canine cardiac Purkinje fiber preparations. METHODS: Fiber preparations (n = 29) were superfused with Krebs-Ringer solution and stimulated at 40-60 pulses/min at 30 degrees C in the absence and presence of 0.55% and 1.01% isoflurane or 0.27% and 0.78% halothane. Isometric tension (CF), and intracellular Ca2+ transients (luminescence, L) were measured after microinjecting the Ca2+ sensitive photoprotein aequorin into Purkinje fibers. Peak CF and peak L, rate of rise (slope) of CF and L, time to attain peak CF and L, and duration of CF and L at half-peak CF and L, were measured at 5 mM extracellular CaCl2. Changes in peak CF and peak L also were measured during incremental increases in CaCl2 from 3.6 to 9.0 mM. RESULTS: Both anesthetics depressed peak CF and peak L and the rate of increase in peak CF and L in a concentration-dependent fashion, and effects of halothane were greater than those of isoflurane. Time to attain peak L and duration of L at half-peak L was decreased or unchanged by isoflurane and was increased by halothane, whereas time to attain peak CF and duration of CF at half-peak CF was shortened by both. The change in peak CF response as a function of the change in peak L with increasing extracellular CaCl2 was attenuated similarly by both halothane and isoflurane. CONCLUSIONS: Halothane depresses peak CF and Ca2+ transients and prolongs Ca2+ transients more than does isoflurane at equivalent minimum alveolar concentration in Purkinje fibers. This suggests Ca2+ concentration is differentially altered by anesthetics in this tissue. Peak CF at equivalent peak Ca2+ transients, however, appears to be attenuated similarly by both anesthetics. These differences in anesthetic effect are qualitatively similar to those found in cardiac tissue of other species. These findings add to our understanding of effects of volatile anesthetics on contractile properties and myoplasmic Ca2+ in cardiac Purkinje fibers. PMID- 8010479 TI - Antinociceptive effects of spinal cholinesterase inhibition and isobolographic analysis of the interaction with mu and alpha 2 receptor systems. AB - BACKGROUND: Spinal cholinergic receptors have been shown to have a potent antinociceptive action, an effect that can be mimicked by spinal cholinesterase inhibitors. We (1) characterized the cholinergic receptor system through which intrathecally applied cholinesterase inhibitors produce their antinociceptive effect and (2) examined their interaction with spinal mu opioid and alpha 2 adrenergic receptors. METHODS: Rats were prepared with chronic intrathecal catheters and the nociceptive threshold was assessed by the use of the radiant heat-evoked hind paw withdrawal. RESULTS: Spinal administration of neostigmine, edrophonium, carbachol, clonidine, and morphine produced a dose-dependent increase on the thermally evoked hind paw withdrawal latency. The order of potency (dose producing a 50% effect, in nanomoles) was morphine (1.1) = neostigmine (1.2) > clonidine (4.4) > carbachol (15) >> edrophonium (112). Spinal pretreatment with atropine (35 nmol) attenuated the antinociceptive effect of intrathecal carbachol (55 nmol), neostigmine (15 nmol), and edrophonium (500 nmol) but did not affect the potency of intrathecal morphine (15 nmol) or clonidine (435 nmol). In addition, intrathecal pretreatment with naloxone (31 nmol) and yohimbine (28 nmol) attenuated the effects of intrathecally administered morphine and clonidine, respectively, but did not significantly affect the potency of carbachol, neostigmine, or edrophonium. The nicotinic receptor antagonist mecamylamine (60 nmol) did not affect thermal nociception. Isobolographic analysis revealed a synergistic interaction after the coadministration of neostigmine-clonidine (P < 0.001), edrophonium-clonidine (P < 0.0001), and edrophonium-morphine (P < 0.01) mixtures. Neostigmine-morphine exhibited simple additivity. CONCLUSIONS: These data indicate that analgesia after spinal cholinesterase inhibition is mediated through muscarinic, but not nicotinic cholinergic, opioid, or alpha 2-adrenergic receptor systems, and that these spinal effects of cholinesterase inhibition interact synergistically with the antinociceptive effects of intrathecal mu and alpha 2 agonists. PMID- 8010482 TI - Volatile anesthetic-induced efflux of calcium from IP3-gated stores in clonal (GH3) pituitary cells. AB - BACKGROUND: Many hormones and neurotransmitters produce their effects by stimulating the generation of inositol 1,4,5-trisphosphate (IP3), a chemical second messenger that releases Ca2+ from intracellular stores. Interruption of this pathway is a potential mechanism through which volatile anesthetics might inhibit chemically mediated communication between cells. This study used GH3 cells (a clonal cell line) as a model system in which to characterize the effects of volatile anesthetics on IP3-induced mobilization of Ca2+ from intracellular stores. METHODS: Intracellular Ca2+ concentration ([Ca2+]i) was continuously monitored in suspensions of GH3 cells at 37 degrees C using the fluorescent Ca2+ indicator Fura-2. Thyrotropin releasing hormone (TRH) was used to discharge IP3 sensitive intracellular Ca2+ stores. The effects of halothane, isoflurane, and octanol on TRH-induced Ca2+ mobilization were assessed as a function of time and anesthetic concentration. To distinguish between anesthetic effects on Ca2+ uptake and Ca2+ release, experiments were performed using thapsigargin (a Ca(2+) ATPase inhibitor) to inhibit Ca2+ uptake into IP3-sensitive stores. RESULTS: Halothane increased resting [Ca2+]i and caused a time- and concentration dependent inhibition of TRH-induced increases in [Ca2+]i (IC50 = 0.6 mM). Thapsigargin, in concentrations that completely inhibit Ca2+ uptake by IP3 sensitive stores, also caused a time-dependent reduction in the [Ca2+]i response to TRH; the time constant of this decay describes the rate of spontaneous leak of Ca2+ from IP3-sensitive stores (tau = 98 +/- 9 s). In the presence of thapsigargin, halothane produced concentration-dependent increases in the rate of leak from IP3-sensitive stores (tau = 74 +/- 12 and 46 +/- 6 s at 0.5 and 1.0 mM halothane, respectively). Isoflurane and octanol also produced concentration dependent inhibition of the [Ca2+]i response to TRH. CONCLUSIONS: Halothane causes a concentration-dependent leak of Ca2+ from IP3-sensitive stores, leading to depletion of the stores and inhibition of IP3-induced increases in [Ca2+]i. This effect occurs at clinically relevant concentrations of halothane (as well as isoflurane and octanol) and may be an important mechanism underlying some of the physiologic effects of volatile anesthetics.